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Tuberculosis_Dataset

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PMC9871572_01

Male

A 66-year-old man presented with fever, cough, excess sputum, and shortness of breath for 1 week. He was given intravenous antibacterial (cephalosporin) treatment for 4 days, but his condition did not improve and dyspnea became more serious. Therefore, the patient came to our hospital where chest CT showed diffuse centrilobular nodules in both lungs, some with a "tree-in-bud" appearance (Figure 1), and multiple enlarged lymph nodes in mediastinum and bilateral axilla (Figure 2). He was then admitted to the hospital. The patient had a history of CLL for 9 years and had received several chemotherapies in the past. His condition was stable in the past year. He has a history of smoking for 30 years. Other medical history was denied. He had no bird exposure and no history of travel outside Wuhan, Hubei, where he lived. At admission, physical examination revealed that temperature was 37.8 C, peripheral blood oxygen saturation (SpO2) was 87% on room air, respiratory rate was 31 breaths/min, and wet rales could be heard on auscultation of both lungs. Multiple soy-sized enlarged lymph nodes could be palpable on both sides of the neck and armpits. Laboratory tests revealed that arterial blood gases at 29% fraction of inspiration O2 (FiO2) showed partial pressure of oxygen (PaO2) 65.6 mmHg, partial arterial pressure of carbon dioxide (PaCO2) 22.8 mmHg, pH 7.43, and oxygenation index (OI; PaO2/FiO2) 226 mmHg. Blood cell analyses, C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR) were examined (Table 1). T-cell spots of tuberculosis infection (T-SPOT.TB) were positive. The detection of mycobacterium tuberculosis in bronchoalveolar (BAL) fluid by polymerase chain reaction (PCR) was negative. Sputum and BAL fluid acid-fast staining were negative. Procalcitonin, immunoglobulin (Ig) E, Mycoplasma pneumoniae IgM, Chlamydia pneumoniae IgM, and 1, 3-beta-D glucan/galactomannan tests were normal. No pathogenic bacteria or fungi were detected in blood, sputum, and BAF fluid cultures. Lymphocyte typing were noted as follows: total T cell 6% (normal, 50-87%), total T-cell number 803/mul (normal, 955-2,860/mul), CD4 + Th-cell proportion 1% (normal, 21-51%), CD4 + Th-cell number 151/mul (normal, 550-1,440/mul), total B-cell 89% (normal, 3-19%), and total B-cell number 12,603/mul (normal, 90-560/mul). The patient was diagnosed with severe pneumonia and type 1 respiratory failure. BAL fluid was collected and sent to the Shenzhen BGI Medical Test Laboratory for metagenomic next-generation sequencing (mNGS), which only supported a diagnosis of S. pneumoniae infection. After admission, the patient's condition improved gradually by giving antimicrobial treatment (moxifloxacin injection, 0.4 g, qd) and other comprehensive treatment measures, including airway clearance and oxygen support. Before discharge, SpO2, blood cell analyses, and related inflammatory markers were reexamined (Table 1), in which SpO2, CRP, and ESR were normal finally, and reexamination of the chest CT showed visible absorption of diffuse centrilobular nodules in both lungs (Figure 1). Three weeks after discharge, a follow-up CT showed that the diffuse centrilobular nodules in both lungs absorbed completely (Figure 1).

streptococcus pneumoniae, case report, centrilobular nodules, chest computed tomography, pneumonia

PMC4802818_01

Male

A 13-year old male, a native of Kerala, India, a student was referred in January 2006 for high grade intermittent fever with rigors and chills of one month duration. He did not complain of cough, hemoptysis, neck swellings or other associated symptoms. He had not traveled outside his district. The young man reported a history of bronchial asthma for last 10 years requiring very occasional treatment with bronchodilators. He did not use alcohol or tobacco. No significant family history except that his father having diabetes. His parents noticed significant weight loss and loss of appetite. On physical examination he was moderately built, anicteric and poorly nourished with pallor with pulse: 108/mt. and temp. 101 F. There was no lymphadenopathy, bleeding manifestations, rash or eschar. Abdominal examination revealed a firm non-nodular liver 5 cm below the right costal margin and an enlarged spleen of 10 cm below the left costal margin (Fig. 1). No ascites was noted. Optic fundi examination was normal. His CBC on admission (01/29/06) was showed a leukocyte count of 1000/mm3, platelet count 17,000/mm3 and Hb 7.7 g/dL. Repeated on 02/05/06, the CBC revealed leukocyte count of 500, platelet count 25,000 and Hb 6.2. Urine analysis was normal. Liver function tests showed normal ALT (33 IU/L) and total bilirubin (0.2 mg/dL) with low albumin (2.5 g/dL), total protein (5.8 g/dL) and mildly elevated alkaline phosphatase (240 IU/L). A tuberculin skin test was negative. HIV ELISA, hepatitis B surface antigen, monospot and ANA were all negative. A chest X-ray was unremarkable. An abdominal ultrasound confirmed hepatosplenomegaly and also found enlarged paraaortic lymph nodes and ascites which were felt to be suggestive of lymphoma. A bone marrow aspiration was interpreted as showing maturation arrest and a bone marrow trephine biopsy was done. The patient's overall clinical status worsened. He continued to be febrile, and developed epistaxis, and purpurae as well as enlargement of several cervical lymph nodes. He was supported with packed RBC and platelet rich plasma. Urine and blood cultures for common bacteria were negative and echocardiogram was unremarkable. High temperature spikes of 101-105 F, weight loss and mucosal bleeds persisted. At that point, his bone marrow trephine biopsy pathology was reported to show the presence of epithelioid cell granulomata with Langhans giant cells and focal necrosis consistent with tuberculosis (Fig. 2). AFB stain was negative. Antituberculous treatment (ATT) with a combination of isoniazid, rifampin, ethambutol pyrazinamide was initiated. The patient developed an urticarial rash with wheezing. Suspecting hypersensitivity, his ATT was changed to ofloxacin, ethambutol and streptomycin for one month and then switched back to the original therapy which he then tolerated without incident. The young man became afebrile after 3 weeks and his blood counts slowly improved. He was continued on the 4 drug ATT for 2 months after restarting and then switched to the combination of isoniazid and rifampin for 10 additional months. Follow up laboratory results are given in Table 1. On follow up after 6 months, he was afebrile and had normal growth milestones. His abdominal ultrasound examination documented decreasing size of his liver and spleen. The final diagnosis of extrapulmonary tuberculosis with hepatosplenomegaly and bone marrow infiltration with pancytopenia was made. In 2015, nine years after presentation of his illness, he remained healthy, asymptomatic and weighing 64 kg.

esr, erythrocyte sedimentation rate, extrapulmonary, fuo, fuo, fever of unknown origin, hypersplenism, massive splenomegaly, pancytopenia, tuberculosis

PMC9235427_01

Unknown

A 1-year-7-month-old infant presented with shortness of breath since 1 week before admitted to hospital. The patient had a cough for the past 1 month. Intermittent fever history was found for the last 6 months. There were noticeable lumps in the neck that slowly grows over the past 8 months from the size of a marble to 5 x 3 cm in size, conglomerated and well-bordered. No history of seizure, projectile vomiting, TB contact, nor family history of malignancy. History of full-term vaginal delivery assisted by a midwife, with normal birth weight and complete immunization. There was weakness in both legs and right hand for the past 4 months and a nonenhanced head CT from a previous hospital revealed multiple masses in the pons, right basal ganglia and left thalamus; bilateral temporoparietooccipital vasogenic edema with bilateral coronary suture diastasis (sign of increased intracranial pressure) [Figure 1]. Laboratory findings showed lower hemoglobin level (6.4 gr/dl), higher white blood count (22.3 x 103/mm), lower albumin (2.7 gr/dl), and lower natrium index (127 mmol/L), while other whole blood cell test and other blood biochemical indexes were within normal ranges. The anteroposterior chest radiograph revealed mass density in the left lung field [Figure 2]. Then chest CT imaging was recommended for further evaluation. In the nonenhanced chest CT, a large pulmonary mass was found at the inferior lobe of the left lung with multiple calcified lymphadenopathies and signs of parenchymal consolidation. According to these manifestations, the authors suspected the mass was giant tuberculoma accompanied by mediastinal lymphadenopathies and bacterial pneumonia [Figure 3]. Cervical ultrasound showed multiple calcified lymphadenopathies in both cervical regions [Figure 4]. Brain MRI with contrast showed multiple lesions in the midbrain, right occipital lobe, and right caudate nucleus suggesting tuberculoma, and focal leptomeningitis in the bilateral occipital region [Figure 5]. The following day, Mantoux test was performed with negative induration, but microscopic test from gastric aspiration showed a positive acid-fast bacillus (AFB) smear proving an active pulmonary TB. The patient then started the initial regimens of anti-TB drugs with isoniazid, rifampicin, ethambutol, and pyrazinamide. An excisional lymph nodes biopsy from the cervical region was then performed to confirm the diagnosis. Histopathological review of the lumps concluded a chronic granulomatous lymphadenitis and supported a TB infection [Figure 6]. However, several days after the biopsy procedure, the patient's condition worsened followed by desaturation, bradycardia, and finally passed away.

infant, mycobacterium tuberculosis, tuberculoma

PMC9402927_01

Female

The neonate's father was 33 years old at the time of the boy's birth and in good health, and the boy's mother was 35 years old. There was a history of pregnancy, with the mother having undergone IVF-ET procedures and producing twins, and with premature rupture of membranes at 20 weeks of gestation. During the current pregnancy, the mother suffered from connective tissue disease and underwent premature rupture of membranes more than 6 days before delivery; and the child was born with clear amniotic fluid of approximately 30 ml. There had been numerous cases of M. tuberculosis infection in the families of both parents, the mother had been infertile for many years; both of her pregnancies were via IVF/ET, each resulting in preterm births. The mother complained that although other infectious diseases were investigated during her IVF treatment, tuberculosis was not evaluated; and there was a history of persistent cough 1 month before delivery. We therefore recommend that a mother suspected of having tuberculosis be sent to a higher specialized hospital as soon as possible to complete the relevant examinations. The mother was ultimately diagnosed with pelvic tuberculosis at the Guangzhou Chest Hospital (a superior hospital) and required conventional treatment.

mycobacterium tuberculosis, congenital tuberculosis, in vitro fertilization-embryo transfer, infection, neonate

PMC9852041_01

Female

A 46-year-old female patient presented with a complaint of left lower back pain for one month. One month prior, the patient had developed intermittent left lumbago without radiation pain. She had no urinary irritation, hematuria, fever, night sweats, or other uncomfortable feelings. She had a history of transvaginal myomectomy 7 years ago, left lumbar impact injury 9 years ago, and smoking for 10 years. She denied a history of hepatitis, tuberculosis, hypertension, diabetes, and coronary heart disease. There was no percussion pain in the double renal region, and a 6 x 6 cm mass in the left abdomen could be deeply palpated. In additional, there was no tenderness in the ureteral area or edema in either lower limb. An auxiliary examination revealed the following. Three-phase enhanced CT of the kidney showed decreased perfusion of the left kidney and a cystic low-density shadow in the left renal hilum, with a CT value of approximately 5 +- 10 HU and size of 7.4 x 7.4 cm. There were flocculent and high-density shadows in the cyst; however, there was no enhancement in the lesion and slight enhancement in the wall. In addition, the left renal pelvis was dilated, with no abnormal density shadow and a clear perirenal fat space. A small amount of fluid density under the left renal capsule were observed in the images. In general, no significant differences were found in the three-phase enhancement images. No abnormalities were observed in the right kidney. (Figure 1) Pulmonary CT findings were as follows. Nodules were observed under the pleura of the upper lobe of the right lung with a diameter of approximately 3 mm, and a punctate high-density shadow was observed in the upper lobe of the right lung. No abnormalities were found in the abdominal aorta, bilateral iliac artery, bilateral iliac vein, or inferior vena cava. On transvaginal three-dimensional ultrasound, cervical echo was found to be non-uniform. Routine blood examination showed no obvious abnormalities; blood, liver, kidney, and blood coagulation function were normal. The urine routine test results were abnormal: the erythrocyte count was 50.7/mul and leukocyte count was 171.8/mul. After comprehensive analysis, the admission diagnosis included a left renal tumor, left renal hydronephrosis, and left renal subcapsular effusion. After admission to our hospital, perioperative preparation improved, and robot-assisted radical nephrectomy was performed under combined intravenous infusion and inhalation anesthesia. We used the da Vinci Xi surgical system of the fourth generation to perform the radical nephrectomy. The transperitoneal approach was adopted instead of the traditional retroperitoneal access approach to view the large tumor. The patient was placed in a lying position with the right oblique at 45 . The incision was at the lateral border of the left rectus abdominis under the 3 cm of the umbilical horizontal line. By cutting the subcutaneous tissue of the skin layer by layer, the sheath of the rectus abdominis, and the peritoneum, we put the first 8 mm trocar into the abdominal cavity, which connected to the robot's third arm, placing the monopolar curved scissors, with keeping the pneumoperitoneum pressure at the 14 mmHg level. Laparoscopy was inserted and the other trocars were established under direct vision. The second 8 mm trocar was established at the width of the two fingers under the xiphoid process, which connected to the robot's first arm, placing the maryland forceps bipolar. The third 8 mm trocar was established at the equidistant position between the above two trocars, which connected to the robot's second arm, placing the laparoscopic lens. The area among the trocars and the operative region was kept as an isosceles triangle. Next, the fourth trocar was established at the position of the 2 cm medial to the iliac crest, which connected to the robot's fourth arm, placing a large needle driver. Finally, we established the fifth 10 mm trocar under the umbilicus as an auxiliary port. (Figure 2C) After examination, it was revealed that approximately 10 cm of the round eminence of the splenic curvature of the colon was protruding into the abdominal cavity. After releasing part of the adhesion, the descending colon adhered to the lateral abdomen, and the left peritoneum was cut along the para-colonic groove. The adhesion between kidney and surrounding tissue was severe, and the adhesion around the tumor was also serious, making it difficult to separate. The nature of the tumor was difficult to judge due to wound bleeding, the unclear relationship between between the tumor and kidney, and serious adhesion of the tumor with the psoas major muscle. Because the possibility of malignancy was high, we performed radical resection of the left kidney, including the tumor and part of the ureter. Dissociating the genital vein, and going upstream along it to the renal hilum, then we saw the renal vein. After using Hem-o-Lok clips to disconnect the genital vein, we then separated the renal vein and dissociated the renal artery in the rear. Next, clipping the renal artery and vein with Hem-o-Lok clips, we dissociated the inferior pole of the kidney to sever the ureter. Finally, with preserving the adrenal gland, the left kidney and tumor was removed completely. In the gross specimen, a mass measuring 7 x 7 cm was observed near the hilum of the left kidney and was associated with the ureter. (Figure 2A) After dissection along the vertical axis, there was an outflow of yellowish gelatinous material, and no neoplasm invasion was found in the renal pelvis or ureter. (Figure 2B) During surgery, approximately 800 ml blood was lost; therefore, 400 ml of plasma and 4 U of red blood cells were infused, and no transfusion reaction was observed. Pathology reports revealed that the volume of the left kidney was 11 x 5 x 7 cm, and the volume of the gray-white cystic mass was 7 x 6 x 5 cm at one pole. There was a large amount of mucus in the tumor, which was a focal grayish yellow color, similar to necrosis. There was a local grayish red color around the kidney, and part of the ureter was adherent. The ureter length was 5 cm, and the broken-end diameter was 0.6 cm. Microscopically, a wide range of mucus lakes was observed, in which floating and irregular glands showed large, deep staining of the tumor nucleus and obvious atypia. The image showed mucinous epithelium and a large amount of mucus. (Figure 3F) Immunohistochemical results were as follows: CDX-2(+), Villin(+), CK7(-), CK20(+), CEA(+), MUC2(+), MUC5AC(+), ER(-), PR(-), P16(-), and CA125(-). (Figures 3A-E) Low-grade mucinous adenocarcinoma of the left kidney was pathologically diagnosis; however metastasis was not diagnosed, suggesting the clinical examination of the appendix. No cancer was found at the end of the ureter or vascular end of the renal hilum. Results of the routine blood examination on the first day after surgery were abnormal: the white blood cell count was 10.5 x 109/L and percentage of neutrophils was 85.9%. The catheter was removed on the second day after surgery. The CT of the upper, middle, lower abdomen was reexamined on the fourth day after surgery. A low-density shadow in the left accessory area, with a small amount of high-density shadow in the pelvic cavity, was observed; furthermore, no abnormalities were found in the other organs. The drainage tube was removed on the fifth day postoperatively, and the patient was discharged without any complaints of discomfort. Our patient was very satisfied with our surgical method and therapeutic measures. There was no special discomfort after the operation, and she recovered quickly, feeling better than before. She suggested that we deal with her tumor properly and timely.

cystadenocarcinoma, kidney, mucinous, primary, robot-assisted surgery

PMC7288794_01

Female

A 64-year-old Caucasian woman, whose prior medical history was significant for type 2 diabetes mellitus and hypertension, presented to medical attention in mid-2017 with intermittent left upper quadrant abdominal pain and diarrhea of several months duration. Laboratory studies included a normal chemistry panel and an unremarkable complete blood count (CBC) with the exception of a modestly elevated platelet count of 480 x 109 cells/L (normal, 150-400 x 109 cells/L). After 5 weeks of persistent gastrointestinal symptoms, a CT scan of the abdomen identified a hypodense splenic lesion measuring 2.7 cm and no other abnormalities. A diagnosis of sclerosing angiomatoid nodular transformation of the spleen was favored over other potential etiologies. Five months later, she presented to medical attention complaining of intense abdominal pain, diarrhea, and 20-pound weight loss, which she attributed to increasing pain with eating as well as early satiety. She did not have fevers or night sweats. Her physical exam was notable for the absence of palpable lymphadenopathy or splenomegaly, and her CBC and comprehensive metabolic panel, including serum LDH, were all within normal limits. Her hemoglobin A1C was 6.4% (normal, 4.0%-5.6%). A CT scan of the abdomen showed left-sided colitis, no pathologically enlarged lymph nodes, and an enlarging splenic lesion. An abdominal multi-phase magnetic resonance imaging (MRI) showed the splenic lesion to be 3.5 cm x 4.9 cm in size, multi-lobulated, non-vascular, and with progressive heterogeneous enhancement in the spleen (Figure 1A-C). For her colitis, she received empiric antibiotics consisting of ciprofloxacin and metronidazole, and her abdominal discomfort gradually improved. Given her changing radiologic findings, medical, surgical, and interventional radiology specialists were consulted to address the concern for splenic infection versus occult malignancy. She was assessed for Toxoplasma gondii and Echinococcosis infection by immunoglobulin titers and for Mycobacterium tuberculosis with blood cultures and Quantiferon-TB Gold release assay. C-reactive protein and erythrocyte sedimentation rate were within normal ranges. Flow cytometry (fluorescence-activated cell sorting [FACS]) analysis from peripheral blood showed no abnormal B-cell, T-cell, or natural killer (NK) cell populations. Our consultants favored laparoscopic splenectomy as both a diagnostic and therapeutic intervention, and prior to surgery, she received vaccinations for Haemophilus influenzae type b, meningococcal meningitis, and Streptococcus pneumoniae. Two months following treatment of her colitis, she underwent an uneventful splenectomy and within a few days after the operation, her persistent left upper quadrant pain had resolved. Examination of the spleen revealed a nearly 5 cm mass (Figure 1D). Tumor cells were positive for CD20, BCL6, MUM1, and BCL2 by immunohistochemistry and negative for AE1/AE3, CD3, and CD10. The Ki-67 proliferative index was expressed in nearly 100% of B-cell nuclei (Figure 2A to D). The FACS of the splenic tissue showed a monoclonal B-cell population. Fluorescent in situ hybridization (FISH) studies showed abnormal signaling; the MYC probe set showed signal fusions suggesting loss of an MYC locus, and the t (14; 18) probe set showed loss of the BCL2 locus and a gain of the 5-prime IGH locus and no translocations involving MYC, BCL2, and/or BCL6 (double or triple hit NHL). A subsequent posterior iliac crest bone marrow biopsy did not show lymphoma, and a follow-up 18fluorodeoxyglucose positron emission tomography/computerized tomography (18FDG-PET-CT) scan showed no abnormal uptake. The patient was diagnosed with stage IE DLBCL [Stage IE refers to the Lugano classification of DLBCL (single extra-lymphatic organ/site)] for which we recommended 4 cycles of adjuvant rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) chemo-immunotherapy after hepatitis B and C serology returned non-reactive. She declined treatment recommendations, and 3 years later, she remains without evidence of lymphoma.

splenic lymphoma, evaluation, splenic nodules, treatment

PMC9922857_02

Unknown

Preliminary anteroposterior (Figure 1A) and lateral (Figure 1B) radiograph examinations of the right hip joint indicated that the femoral head had disappeared and that the margins of the femoral neck and acetabulum were incomplete, which were further confirmed by 3D reconstruction images (Figure 1C) and CT scan images (Figures 1D,E). In particular, the 3D reconstruction and CT scan images clearly demonstrated the range of local osteolysis involving the acetabulum and femoral neck. MRI images (Figures 1F-I) showed hypointensity on T1-weighted images, extensive hyperintensity on fat-suppressed T2-weighted images, and massive joint effusion in the right hip joint. To further clarify the progression of the disease, ECT examination (Figure 2) was performed and the results showed increased focal concentrations of radiotracers in the right femoral head, femoral neck, and acetabulum. Therefore, we highly suspected that this patient may be diagnosed with a malignant bone tumor with aggressive osteolytic lesions. In addition, the chest radiograph was normal, and no obvious signs of tuberculosis were found. Laboratory blood tests showed normal levels of leukocytes, neutrophil granulocyte ratio, hypersensitive C-reactive protein, erythrocyte sedimentation rate, serum calcium, phosphorous, alkaline phosphatase, and parathyroid hormone. Oncology indicators such as alpha fetoprotein, carcinoembryonic antigen and PSA were all within the normal range. The T-SPOT test was negative. To further clarify the diagnosis, an open biopsy of the right hip joint was performed under general anesthesia. A total of 6 cm3 tissues were obtained from the right femoral neck, synovial membrane, and acetabulum. Subsequent histological examinations showed that the necrotic bone tissue was accompanied by focal aggregation of osteoclasts, giant cells and plasma cells without cellular atypia, some proliferative thin-walled capillaries and lymphatic structures, and replaced by fibrous connective tissue (Figure 3). Combined with clinical manifestations, laboratory blood tests, radiological features and histopathology examinations, the patient met seven out of the eight diagnostic criteria for GSD proposed by Heffez et al. (Table 1). Eventually, the patient was diagnosed with GSD. The patient was then treated with medication, including bisphosphonates (4 mg/week, iv), vitamin D (600 UI/day), and calcium (600 mg/day) for one month. The surgical criteria for total hip replacement in patients with GSD were considered as follows: (i) the patient was 70 years old; (ii) The GSD lesions had involved the acetabulum and the neck of the femur, and in a serious case, the femoral head had completely disappeared. (iii) Contraindications to surgery have been ruled out by relevant examinations. (iii) The patient has a strong need to restore lower limb motor function. We first completely removed the GSD-accumulated bone with the assistance of intraoperative pathologic examination, and then fitted a total hip arthroplasty rather than femoral head arthroplasty to account for the GSD lesions that had accumulated in the acetabulum. To restore the normal walking function of the lower limbs, we performed complete excision of the necrotic tissue followed by total hip arthroplasty. At the 3-year follow-up after surgery, the patient had no pain in the right hip when walking long distances or bearing weight. Radiographs showed that the hip prosthesis was in place and not loose. Moreover, no signs of recurrence were observed in the right hip joint (Figure 4).

arthroplasty, bisphosphonates, gorham-stout disease, hip joint, histopathological, radiological features

PMC10091461_01

Male

Huang et al. present a case of a 10-year-old immunocompetent boy presenting with a 5-day history of intermittent, left-sided chest pain, having a left lung nodule caused by Streptococcus intermedius. The nodule was identified by chest radiography. The cultures of aspirates of the nodule were negative but the germ was identified by metagenomic next-generation sequencing. He was given proper antibiotics and did not require a surgical intervention. The authors highlight the rarity of the case and the importance of metagenomic next-generation sequencing in the diagnostic process. Zhuang et al. reported a case of Congenital tuberculosis in a neonate following in vitro fertilization-embryo transfer. They performed pathogenic microorganism metagenomic analysis and isolated the Mycobacterium tuberculosis complex in a preterm infant poorly responding to treatment. Subsequently, maternal pelvic tuberculosis was confirmed. Since, in vitro fertilization (IVF) treatment and pregnancy can exacerbate latent tuberculosis, identifying maternal tuberculosis during IVF treatment using metagenomic approach can be a useful option. Rodriguez et al. reported a case of an unusual pneumonia pathogen, detected by plasma cell free next-generation sequencing in an immunocompetent adolescent with acute respiratory distress syndrome. This case details a rapid diagnosis of legionella pneumonia causing severe acute respiratory distress syndrome (ARDS) in an otherwise healthy adolescent through plasma microbial cell-free DNA next generation sequencing (mcfDNA-NGS). Diagnosis by mcfDNA-NGS of this unexpected pathogen led to narrowing of antimicrobials and this novel technology can be a useful tool for paediatric infectious disease diagnosis.

case report, diagnosis, infectious diseases, pediatrics, rare presentations

PMC5051476_03

Female

A 68 year-old female patient, with surgical treatment for duodenal ulcer. The postoperative outcomes were difficult, with ARDS and prolongued mechanical ventilation and tracheostomy. 30 days after the tracheostomy, the tracheo-esophageal fistula caused by balloon compression on the tracheal wall was discovered. Thoracic scans (Fig. 15), bronchoscopic and esophagoscopic exams showed a tracheo-esophageal fistula at cervical trachea, at the level of previous tracheostomy. Treatment Horizontal cervicothomy "en verre Bordeaux". The dissection of trachea and esophagus revealed the fistula and its resection, together with a small portion of the membranous wall of the trachea. Tracheal suture with 4.0 resorbable and esophagus with resorbable 4.0, duble layer and interposition between these 2 suture lines of muscle pedicle (Fig. 16). Postoperative outcomes were favorable. After aproximatively 6 months, the patient requested temporary Montgomery stent and bronchial dilatation due to a tracheal stenosis developed at the level of tracheostomy. Eso-respiratory fistula is an abnormal communication between esophagus and the respiratory tree. The ethiology is: congenital (with or without esophagus athresia) or aquired (trauma, iatrogenic or neoplasia) []. This etiology type (except for neoplasic fistulas) is frequently correlated with anatomo-clinical forms of eso-bronchial fistula: - Congenital eso-respiratory fistulas are usually tubular, longues, and facilitate surgery []. - Infectious eso-respiratory fistulas (tuberculosis, empyeme, and mediastinitis) are diverticularly shaped, sclerous; all these caracteristics make surgery very difficult. - Traumatic eso-bronchial fistulas are the most difficult to dissect and to suture []. The presence of eso-respiratory fistula caused the aspiration of esophageal content into the bronchial tree, leading progressively to congestion, bronchial and lung infections with bronchial occlusion, athelectasy, respiratory distress and exitus. Usually, eso-respiratory fistulas are followed by piosclerosis and lung abscess []. Clinical features: productive cough (after water or food ingestion), expectoration with previous ingested food. In over 70% cases, eso-respiratory fistulas could be diagnosed after barium ingestion X-Ray exam. Esophageal endoscopy and bronchoscopyc exams are useful to evaluate these fistulas, especially after the instillation of a coloured solution (metilen blue). With regard to fistulas' etiology, therapy is neccessarily surgical [] and should not be delayed. Spontaneus healing of fistula is seldom (we could say, exceptional) and fistulas' occlusion with acrylic polymer or electrocauterisation are controversial. Paleativ procedures such as endotracheal or esophageal stents could be experimented on inoperable patients []. However, these procedures depend on ethiology and they take place with or without esophageal by-pass.

PMC6136468_01

Female

A 5-year-old girl who had no previous medical history was admitted to our hospital with a right groin mass for 2 months and abdominal distension for 15 days. Her symptoms were accompanied by occasional umbilical pain, vomiting, and diarrhea. Physical examination showed acute facial features, malnutrition, abdominal swelling, apparent tenderness, a mass approximately 4 x 3 x 2 cm in size in the right inguinal region, and negative Grey Turner sign and Cullen sign. Routine blood test revealed white blood cells 2.97 x 109/L, neutrophils 47.2%, red blood cells 4.88 x 1012/L, platelets 714 x 109/L, and C-reactive protein 2.06 mg/L. Abdominal enhanced computed tomography (CT) revealed the following findings: (1) the pancreatic duct was significantly dilated, and the surrounding pancreatic head space was unclear; (2) a cystic low-density shadow was observed in the head of the pancreas (Figure 1); (3) massive peritoneal effusion was observed; (4) patchy lymph node enhancement and enlargement were observed in the mesentery; and (5) intestinal aggregation in the upper abdomen along with thickening and enhancement of the bowel wall was observed. Chest CT revealed increased lung markings and no signs of TB. After admission, the patient presented with diffuse abdominal distension. Laboratory tests indicated pancreatitis (serum lipase 3167 U/L and serum amylase 720 U/L). Serum cancer antigen- (CA-) 125 was increased to 484.5 U/mL (normal is less than 35 U/mL). An abdominal puncture was performed three days after admission. Ascites was red and yellow. Qualitative protein was positive. No acid-fast bacilli were identified via ascites smear. The anti-TB antibody in serum was negative. The purified protein derivative of the tuberculin test and interferon-gamma release assay were negative. No tumor cells were identified in the ascites, and there was no bacterial growth in the ascites for 48 hours. Seven days after admission, the patient underwent laparoscopic exploration. In total, 3600 mL of bloody ascites was present in the peritoneal cavity. Pale and fish-like masses were found. A wide and dark-red flocculent area was visible. Pathological examination revealed an inflammatory exudate. The results of periodic acid-Schiff staining, methenamine silver staining, and acid-fast staining were negative. No bacteria or tubercle bacilli were found in the ascites cultures. Using polymerase chain reaction (PCR), Mycobacterium tuberculosis DNA was identified in the resected abdominal mass. Therefore, the diagnosis of pancreatic TB was made. Fasting, somatostatin, omeprazole, and total parenteral nutrition therapy were administered. Rifampicin (10 mg/kg/day), pyrazinamide (20 mg/kg/day), and isoniazid (10 mg/kg/day) were prescribed. Three weeks later, abdominal pain, abdominal distension, cough, fever, nausea, vomiting, and diarrhea had resolved. The patient was discharged. Two weeks after discharge, pain around the umbilicus and periumbilical tenderness were reported with nausea and vomiting. Abdominal ultrasonography revealed large pancreatic cysts. The diagnosis of a pancreatic pseudocyst was made, and ultrasound-guided puncture drainage was performed. Giant cystic lesions as thick as the wall and approximately 12 x 9 x 10 cm in size were observed by intraoperative ultrasonography. Approximately 500 mL of brown cyst fluid was expelled. On day 4 after the operation, the patient's general condition was good, and her vital signs were stable. Therefore, she was discharged again. Outpatient antitubercular therapy consisted of isoniazid, rifampicin, and pyrazinamide for 4 months and subsequently isoniazid and rifampicin for 8 months. At the one-year outpatient follow-up visit, her appetite improved, and she regained the weight she had previously lost. Abdominal CT showed a significant reduction in the cystic low-density shadow of the head and neck of the pancreas (Figure 2). The effect of the antitubercular therapy was significant.

PMC10332418_01

Female

A 34-year-old young lady was admitted to the Department of Rheumatology and Immunology of the 2nd affiliated hospital of Chongqing Medical University (CQMU), Chongqing, China, on May 6, 2021, due to "limb joint pain for more than one month" (Figure 1). More than a month before admission, the patient developed bilateral symmetrical pains in her wrists, elbows, knees, and ankles without obvious causes, along with tenderness. These symptoms were heavier in the morning with stiffness, and slight relieving at afternoon. The involved joints were intermittent swelling, without wandering or joint deformity. During the course of disease, she had no fever, cough, expectoration, abdominal pain, and diarrhea. This lady was with a height of 160cm, and a weight of 55kg (BMI 21.48kg/m2). She was a salesperson, working at a supermarket with central air conditioning. And a dog was raised at the lady's home. She had married without a child. She had no history of smoking or alcohol consumption. There was an allergic history to cephalosporin about 10 years ago. She was born and living in Chongqing for a long time, and she had not gone to other places for a recent year. Physical examination of her whole body showed no abnormal findings. After admission, firstly, the lady's anti-Ro antibody was positive (++), Sjogren's syndrome was suspected. However, no abnormality was found in the parotid gland and bilateral submandibular glands. Therefore, lip mucosa biopsy was performed to further exclude the diagnosis of Sjogren's syndrome. At the same time, ultrasonography of muscle and bone showed that there was some effusion in the joint cavity of the right knee joint. Along with the symptoms of joint pain, rheumatoid arthritis should be considered. Next day, the negative results of anti-cyclic citrullinated peptide (CCP) and rheumatoid factor (RF) helped decrease the possibility of rheumatoid arthritis' diagnosis. Enhanced CT scanning of chest (Figure 2) unexpectedly showed bilateral pulmonary interstitial inflammation, with multiple lymphadenopathies, thus pneumonia was considered (Figure 2A and B). Although the patient had no typical symptoms like fever, cough, expectoration, or shortness of breath, levofloxacin was given empirically with elevated neutrophils (Figure 3A). At the same time, the relevant etiological examination was further arranged; however, these results were successively showed negative (Supplementary Table 2). On the third day, the lady's joint pain was still obvious, so she underwent an intra-articular puncture, fluid extraction, and 1 mL of Diprospan injection into the intra-articular cavity for anti-inflammatory treatment. The pathological results of lip mucosa came back and showed that no lymphocyte aggregation was found. Till then, the diagnosis of Sjogren's syndrome was completely excluded. And the patient's joint pain relived. One week later, a re-examination of chest CT scanning showed that the inflammation of both lungs was smaller, but lymphadenopathies were basically the same as compared to before (Figure 2C and D). After consultation from the respiratory department, a transfer was recommended to clarify the nature of lymphadenopathy. Doppler ultrasonography of superficial lymph nodes detected several enlarged lymph nodes on the right clavicle, with clear boundaries, and the largest one was about 1.6 x 0.7cm. On the eighth day, the patient underwent a bronchoscopy plus endobronchial ultrasound-transbronchial needle aspiration (EBUS-TBNA) operation under general anesthesia. During the operation, a small amount of purulent secretion was found in the patient's trachea and bilateral main bronchus, which was lavaged, washed out, and sent to culture. The lavage fluid in the lower left lobe was sent for exfoliative cytology and Xpert MTB/RIF detection. Microscopically, it can be seen that the bilateral bronchial mucosa of each leaf and segment of this patient was normal, the lumen was unobstructed. And no neoplasm, bleeding, or necrosis tissues were found. Then, the ultrasonic bronchoscope was replaced. EBUS-TBNA exploration showed that the lymph nodes in group N4, N7, R10, and L11 were swollen and fused. The lymph nodes in groups N4, N7, R10, and L11 were punctured with 21G puncture needles for 1, 3, 2, and 3 times, respectively. Necrotic chips and strip tissues were extracted and sent to exfoliated cytology, tNGS and pathological biopsy detection. The whole operation process was smooth. The results of exfoliated cytology showed a few lymphocytes and neutrophils (Figure 3B-E). Pathologist reported squeezed lymphocytes and a few epithelial-like cells (Figure 3F and G). Immunohistochemistry analysis was CK (-), Vim (+), Ki-67 (+) 1%, CEA nidus (+), CK7 (-), and anti-acid staining (-). Xpert MTB/RIF was negative. However, tNGS reported 1225 reads of Legionella pneumophila in the samples of lymph node (Supplementary Table 3). Soon a multidisciplinary team (MDT) including experts in hematology, pathology, rheumatism immunity, respiration, and infection discussed the exact cause of this young lady's hospitalization. Finally, with all the information collected, especially the tNGS results, agreement was made that the patient's condition can be rationally explained by the infection of Legionella pneumophila. Thus, levofloxacin continued. By the 15th day, joint pain of the patient was completely relieved, so she was discharged from the hospital with the advice of another week's oral levofloxacin taking. A month later, not only did the interstitial changes in both lungs were further improved by re-examination of chest CT scanning, but also the enlarged lymph nodes began to shrink (Figure 2E and F). On the 59th day, the patient was followed up at the outpatient department. The symptoms of joint pain did not recur, the interstitial changes of both lungs on chest CT were further improved, and the enlarged lymph nodes were further reduced (Figure 2G and H). During the last follow-up of 141th day, the joint pain still did not recur. The interstitial lesions in both lungs disappeared completely on chest CT, and the enlarged lymph nodes became much smaller (Figure 2I and J).

legionella pneumophila, case report, levofloxacin, precision treatment, tngs, targeted next-generation sequencing

Enhanced chest CT scanning of the patient. Chest CT enhancement showed bilateral interstitial pneumonia especially the right lower lobe under pulmonary window.

PMC10332418_01

Female

A 34-year-old young lady was admitted to the Department of Rheumatology and Immunology of the 2nd affiliated hospital of Chongqing Medical University (CQMU), Chongqing, China, on May 6, 2021, due to "limb joint pain for more than one month" (Figure 1). More than a month before admission, the patient developed bilateral symmetrical pains in her wrists, elbows, knees, and ankles without obvious causes, along with tenderness. These symptoms were heavier in the morning with stiffness, and slight relieving at afternoon. The involved joints were intermittent swelling, without wandering or joint deformity. During the course of disease, she had no fever, cough, expectoration, abdominal pain, and diarrhea. This lady was with a height of 160cm, and a weight of 55kg (BMI 21.48kg/m2). She was a salesperson, working at a supermarket with central air conditioning. And a dog was raised at the lady's home. She had married without a child. She had no history of smoking or alcohol consumption. There was an allergic history to cephalosporin about 10 years ago. She was born and living in Chongqing for a long time, and she had not gone to other places for a recent year. Physical examination of her whole body showed no abnormal findings. After admission, firstly, the lady's anti-Ro antibody was positive (++), Sjogren's syndrome was suspected. However, no abnormality was found in the parotid gland and bilateral submandibular glands. Therefore, lip mucosa biopsy was performed to further exclude the diagnosis of Sjogren's syndrome. At the same time, ultrasonography of muscle and bone showed that there was some effusion in the joint cavity of the right knee joint. Along with the symptoms of joint pain, rheumatoid arthritis should be considered. Next day, the negative results of anti-cyclic citrullinated peptide (CCP) and rheumatoid factor (RF) helped decrease the possibility of rheumatoid arthritis' diagnosis. Enhanced CT scanning of chest (Figure 2) unexpectedly showed bilateral pulmonary interstitial inflammation, with multiple lymphadenopathies, thus pneumonia was considered (Figure 2A and B). Although the patient had no typical symptoms like fever, cough, expectoration, or shortness of breath, levofloxacin was given empirically with elevated neutrophils (Figure 3A). At the same time, the relevant etiological examination was further arranged; however, these results were successively showed negative (Supplementary Table 2). On the third day, the lady's joint pain was still obvious, so she underwent an intra-articular puncture, fluid extraction, and 1 mL of Diprospan injection into the intra-articular cavity for anti-inflammatory treatment. The pathological results of lip mucosa came back and showed that no lymphocyte aggregation was found. Till then, the diagnosis of Sjogren's syndrome was completely excluded. And the patient's joint pain relived. One week later, a re-examination of chest CT scanning showed that the inflammation of both lungs was smaller, but lymphadenopathies were basically the same as compared to before (Figure 2C and D). After consultation from the respiratory department, a transfer was recommended to clarify the nature of lymphadenopathy. Doppler ultrasonography of superficial lymph nodes detected several enlarged lymph nodes on the right clavicle, with clear boundaries, and the largest one was about 1.6 x 0.7cm. On the eighth day, the patient underwent a bronchoscopy plus endobronchial ultrasound-transbronchial needle aspiration (EBUS-TBNA) operation under general anesthesia. During the operation, a small amount of purulent secretion was found in the patient's trachea and bilateral main bronchus, which was lavaged, washed out, and sent to culture. The lavage fluid in the lower left lobe was sent for exfoliative cytology and Xpert MTB/RIF detection. Microscopically, it can be seen that the bilateral bronchial mucosa of each leaf and segment of this patient was normal, the lumen was unobstructed. And no neoplasm, bleeding, or necrosis tissues were found. Then, the ultrasonic bronchoscope was replaced. EBUS-TBNA exploration showed that the lymph nodes in group N4, N7, R10, and L11 were swollen and fused. The lymph nodes in groups N4, N7, R10, and L11 were punctured with 21G puncture needles for 1, 3, 2, and 3 times, respectively. Necrotic chips and strip tissues were extracted and sent to exfoliated cytology, tNGS and pathological biopsy detection. The whole operation process was smooth. The results of exfoliated cytology showed a few lymphocytes and neutrophils (Figure 3B-E). Pathologist reported squeezed lymphocytes and a few epithelial-like cells (Figure 3F and G). Immunohistochemistry analysis was CK (-), Vim (+), Ki-67 (+) 1%, CEA nidus (+), CK7 (-), and anti-acid staining (-). Xpert MTB/RIF was negative. However, tNGS reported 1225 reads of Legionella pneumophila in the samples of lymph node (Supplementary Table 3). Soon a multidisciplinary team (MDT) including experts in hematology, pathology, rheumatism immunity, respiration, and infection discussed the exact cause of this young lady's hospitalization. Finally, with all the information collected, especially the tNGS results, agreement was made that the patient's condition can be rationally explained by the infection of Legionella pneumophila. Thus, levofloxacin continued. By the 15th day, joint pain of the patient was completely relieved, so she was discharged from the hospital with the advice of another week's oral levofloxacin taking. A month later, not only did the interstitial changes in both lungs were further improved by re-examination of chest CT scanning, but also the enlarged lymph nodes began to shrink (Figure 2E and F). On the 59th day, the patient was followed up at the outpatient department. The symptoms of joint pain did not recur, the interstitial changes of both lungs on chest CT were further improved, and the enlarged lymph nodes were further reduced (Figure 2G and H). During the last follow-up of 141th day, the joint pain still did not recur. The interstitial lesions in both lungs disappeared completely on chest CT, and the enlarged lymph nodes became much smaller (Figure 2I and J).

legionella pneumophila, case report, levofloxacin, precision treatment, tngs, targeted next-generation sequencing

Enhanced chest CT scanning of the patient. Chest CT enhancement showed pneumonia of right lower lung was getting smaller under pulmonary window.

PMC10332418_01

Female

A 34-year-old young lady was admitted to the Department of Rheumatology and Immunology of the 2nd affiliated hospital of Chongqing Medical University (CQMU), Chongqing, China, on May 6, 2021, due to "limb joint pain for more than one month" (Figure 1). More than a month before admission, the patient developed bilateral symmetrical pains in her wrists, elbows, knees, and ankles without obvious causes, along with tenderness. These symptoms were heavier in the morning with stiffness, and slight relieving at afternoon. The involved joints were intermittent swelling, without wandering or joint deformity. During the course of disease, she had no fever, cough, expectoration, abdominal pain, and diarrhea. This lady was with a height of 160cm, and a weight of 55kg (BMI 21.48kg/m2). She was a salesperson, working at a supermarket with central air conditioning. And a dog was raised at the lady's home. She had married without a child. She had no history of smoking or alcohol consumption. There was an allergic history to cephalosporin about 10 years ago. She was born and living in Chongqing for a long time, and she had not gone to other places for a recent year. Physical examination of her whole body showed no abnormal findings. After admission, firstly, the lady's anti-Ro antibody was positive (++), Sjogren's syndrome was suspected. However, no abnormality was found in the parotid gland and bilateral submandibular glands. Therefore, lip mucosa biopsy was performed to further exclude the diagnosis of Sjogren's syndrome. At the same time, ultrasonography of muscle and bone showed that there was some effusion in the joint cavity of the right knee joint. Along with the symptoms of joint pain, rheumatoid arthritis should be considered. Next day, the negative results of anti-cyclic citrullinated peptide (CCP) and rheumatoid factor (RF) helped decrease the possibility of rheumatoid arthritis' diagnosis. Enhanced CT scanning of chest (Figure 2) unexpectedly showed bilateral pulmonary interstitial inflammation, with multiple lymphadenopathies, thus pneumonia was considered (Figure 2A and B). Although the patient had no typical symptoms like fever, cough, expectoration, or shortness of breath, levofloxacin was given empirically with elevated neutrophils (Figure 3A). At the same time, the relevant etiological examination was further arranged; however, these results were successively showed negative (Supplementary Table 2). On the third day, the lady's joint pain was still obvious, so she underwent an intra-articular puncture, fluid extraction, and 1 mL of Diprospan injection into the intra-articular cavity for anti-inflammatory treatment. The pathological results of lip mucosa came back and showed that no lymphocyte aggregation was found. Till then, the diagnosis of Sjogren's syndrome was completely excluded. And the patient's joint pain relived. One week later, a re-examination of chest CT scanning showed that the inflammation of both lungs was smaller, but lymphadenopathies were basically the same as compared to before (Figure 2C and D). After consultation from the respiratory department, a transfer was recommended to clarify the nature of lymphadenopathy. Doppler ultrasonography of superficial lymph nodes detected several enlarged lymph nodes on the right clavicle, with clear boundaries, and the largest one was about 1.6 x 0.7cm. On the eighth day, the patient underwent a bronchoscopy plus endobronchial ultrasound-transbronchial needle aspiration (EBUS-TBNA) operation under general anesthesia. During the operation, a small amount of purulent secretion was found in the patient's trachea and bilateral main bronchus, which was lavaged, washed out, and sent to culture. The lavage fluid in the lower left lobe was sent for exfoliative cytology and Xpert MTB/RIF detection. Microscopically, it can be seen that the bilateral bronchial mucosa of each leaf and segment of this patient was normal, the lumen was unobstructed. And no neoplasm, bleeding, or necrosis tissues were found. Then, the ultrasonic bronchoscope was replaced. EBUS-TBNA exploration showed that the lymph nodes in group N4, N7, R10, and L11 were swollen and fused. The lymph nodes in groups N4, N7, R10, and L11 were punctured with 21G puncture needles for 1, 3, 2, and 3 times, respectively. Necrotic chips and strip tissues were extracted and sent to exfoliated cytology, tNGS and pathological biopsy detection. The whole operation process was smooth. The results of exfoliated cytology showed a few lymphocytes and neutrophils (Figure 3B-E). Pathologist reported squeezed lymphocytes and a few epithelial-like cells (Figure 3F and G). Immunohistochemistry analysis was CK (-), Vim (+), Ki-67 (+) 1%, CEA nidus (+), CK7 (-), and anti-acid staining (-). Xpert MTB/RIF was negative. However, tNGS reported 1225 reads of Legionella pneumophila in the samples of lymph node (Supplementary Table 3). Soon a multidisciplinary team (MDT) including experts in hematology, pathology, rheumatism immunity, respiration, and infection discussed the exact cause of this young lady's hospitalization. Finally, with all the information collected, especially the tNGS results, agreement was made that the patient's condition can be rationally explained by the infection of Legionella pneumophila. Thus, levofloxacin continued. By the 15th day, joint pain of the patient was completely relieved, so she was discharged from the hospital with the advice of another week's oral levofloxacin taking. A month later, not only did the interstitial changes in both lungs were further improved by re-examination of chest CT scanning, but also the enlarged lymph nodes began to shrink (Figure 2E and F). On the 59th day, the patient was followed up at the outpatient department. The symptoms of joint pain did not recur, the interstitial changes of both lungs on chest CT were further improved, and the enlarged lymph nodes were further reduced (Figure 2G and H). During the last follow-up of 141th day, the joint pain still did not recur. The interstitial lesions in both lungs disappeared completely on chest CT, and the enlarged lymph nodes became much smaller (Figure 2I and J).

legionella pneumophila, case report, levofloxacin, precision treatment, tngs, targeted next-generation sequencing

Enhanced chest CT scanning of the patient. Chest CT enhancement showed the interstitial changes of both lungs were further improved under pulmonary window.

PMC10332418_01

Female

A 34-year-old young lady was admitted to the Department of Rheumatology and Immunology of the 2nd affiliated hospital of Chongqing Medical University (CQMU), Chongqing, China, on May 6, 2021, due to "limb joint pain for more than one month" (Figure 1). More than a month before admission, the patient developed bilateral symmetrical pains in her wrists, elbows, knees, and ankles without obvious causes, along with tenderness. These symptoms were heavier in the morning with stiffness, and slight relieving at afternoon. The involved joints were intermittent swelling, without wandering or joint deformity. During the course of disease, she had no fever, cough, expectoration, abdominal pain, and diarrhea. This lady was with a height of 160cm, and a weight of 55kg (BMI 21.48kg/m2). She was a salesperson, working at a supermarket with central air conditioning. And a dog was raised at the lady's home. She had married without a child. She had no history of smoking or alcohol consumption. There was an allergic history to cephalosporin about 10 years ago. She was born and living in Chongqing for a long time, and she had not gone to other places for a recent year. Physical examination of her whole body showed no abnormal findings. After admission, firstly, the lady's anti-Ro antibody was positive (++), Sjogren's syndrome was suspected. However, no abnormality was found in the parotid gland and bilateral submandibular glands. Therefore, lip mucosa biopsy was performed to further exclude the diagnosis of Sjogren's syndrome. At the same time, ultrasonography of muscle and bone showed that there was some effusion in the joint cavity of the right knee joint. Along with the symptoms of joint pain, rheumatoid arthritis should be considered. Next day, the negative results of anti-cyclic citrullinated peptide (CCP) and rheumatoid factor (RF) helped decrease the possibility of rheumatoid arthritis' diagnosis. Enhanced CT scanning of chest (Figure 2) unexpectedly showed bilateral pulmonary interstitial inflammation, with multiple lymphadenopathies, thus pneumonia was considered (Figure 2A and B). Although the patient had no typical symptoms like fever, cough, expectoration, or shortness of breath, levofloxacin was given empirically with elevated neutrophils (Figure 3A). At the same time, the relevant etiological examination was further arranged; however, these results were successively showed negative (Supplementary Table 2). On the third day, the lady's joint pain was still obvious, so she underwent an intra-articular puncture, fluid extraction, and 1 mL of Diprospan injection into the intra-articular cavity for anti-inflammatory treatment. The pathological results of lip mucosa came back and showed that no lymphocyte aggregation was found. Till then, the diagnosis of Sjogren's syndrome was completely excluded. And the patient's joint pain relived. One week later, a re-examination of chest CT scanning showed that the inflammation of both lungs was smaller, but lymphadenopathies were basically the same as compared to before (Figure 2C and D). After consultation from the respiratory department, a transfer was recommended to clarify the nature of lymphadenopathy. Doppler ultrasonography of superficial lymph nodes detected several enlarged lymph nodes on the right clavicle, with clear boundaries, and the largest one was about 1.6 x 0.7cm. On the eighth day, the patient underwent a bronchoscopy plus endobronchial ultrasound-transbronchial needle aspiration (EBUS-TBNA) operation under general anesthesia. During the operation, a small amount of purulent secretion was found in the patient's trachea and bilateral main bronchus, which was lavaged, washed out, and sent to culture. The lavage fluid in the lower left lobe was sent for exfoliative cytology and Xpert MTB/RIF detection. Microscopically, it can be seen that the bilateral bronchial mucosa of each leaf and segment of this patient was normal, the lumen was unobstructed. And no neoplasm, bleeding, or necrosis tissues were found. Then, the ultrasonic bronchoscope was replaced. EBUS-TBNA exploration showed that the lymph nodes in group N4, N7, R10, and L11 were swollen and fused. The lymph nodes in groups N4, N7, R10, and L11 were punctured with 21G puncture needles for 1, 3, 2, and 3 times, respectively. Necrotic chips and strip tissues were extracted and sent to exfoliated cytology, tNGS and pathological biopsy detection. The whole operation process was smooth. The results of exfoliated cytology showed a few lymphocytes and neutrophils (Figure 3B-E). Pathologist reported squeezed lymphocytes and a few epithelial-like cells (Figure 3F and G). Immunohistochemistry analysis was CK (-), Vim (+), Ki-67 (+) 1%, CEA nidus (+), CK7 (-), and anti-acid staining (-). Xpert MTB/RIF was negative. However, tNGS reported 1225 reads of Legionella pneumophila in the samples of lymph node (Supplementary Table 3). Soon a multidisciplinary team (MDT) including experts in hematology, pathology, rheumatism immunity, respiration, and infection discussed the exact cause of this young lady's hospitalization. Finally, with all the information collected, especially the tNGS results, agreement was made that the patient's condition can be rationally explained by the infection of Legionella pneumophila. Thus, levofloxacin continued. By the 15th day, joint pain of the patient was completely relieved, so she was discharged from the hospital with the advice of another week's oral levofloxacin taking. A month later, not only did the interstitial changes in both lungs were further improved by re-examination of chest CT scanning, but also the enlarged lymph nodes began to shrink (Figure 2E and F). On the 59th day, the patient was followed up at the outpatient department. The symptoms of joint pain did not recur, the interstitial changes of both lungs on chest CT were further improved, and the enlarged lymph nodes were further reduced (Figure 2G and H). During the last follow-up of 141th day, the joint pain still did not recur. The interstitial lesions in both lungs disappeared completely on chest CT, and the enlarged lymph nodes became much smaller (Figure 2I and J).

legionella pneumophila, case report, levofloxacin, precision treatment, tngs, targeted next-generation sequencing

Enhanced chest CT scanning of the patient. Chest CT enhancement showed pneumonia of right lower lung was getting much smaller under pulmonary window.

PMC10332418_01

Female

A 34-year-old young lady was admitted to the Department of Rheumatology and Immunology of the 2nd affiliated hospital of Chongqing Medical University (CQMU), Chongqing, China, on May 6, 2021, due to "limb joint pain for more than one month" (Figure 1). More than a month before admission, the patient developed bilateral symmetrical pains in her wrists, elbows, knees, and ankles without obvious causes, along with tenderness. These symptoms were heavier in the morning with stiffness, and slight relieving at afternoon. The involved joints were intermittent swelling, without wandering or joint deformity. During the course of disease, she had no fever, cough, expectoration, abdominal pain, and diarrhea. This lady was with a height of 160cm, and a weight of 55kg (BMI 21.48kg/m2). She was a salesperson, working at a supermarket with central air conditioning. And a dog was raised at the lady's home. She had married without a child. She had no history of smoking or alcohol consumption. There was an allergic history to cephalosporin about 10 years ago. She was born and living in Chongqing for a long time, and she had not gone to other places for a recent year. Physical examination of her whole body showed no abnormal findings. After admission, firstly, the lady's anti-Ro antibody was positive (++), Sjogren's syndrome was suspected. However, no abnormality was found in the parotid gland and bilateral submandibular glands. Therefore, lip mucosa biopsy was performed to further exclude the diagnosis of Sjogren's syndrome. At the same time, ultrasonography of muscle and bone showed that there was some effusion in the joint cavity of the right knee joint. Along with the symptoms of joint pain, rheumatoid arthritis should be considered. Next day, the negative results of anti-cyclic citrullinated peptide (CCP) and rheumatoid factor (RF) helped decrease the possibility of rheumatoid arthritis' diagnosis. Enhanced CT scanning of chest (Figure 2) unexpectedly showed bilateral pulmonary interstitial inflammation, with multiple lymphadenopathies, thus pneumonia was considered (Figure 2A and B). Although the patient had no typical symptoms like fever, cough, expectoration, or shortness of breath, levofloxacin was given empirically with elevated neutrophils (Figure 3A). At the same time, the relevant etiological examination was further arranged; however, these results were successively showed negative (Supplementary Table 2). On the third day, the lady's joint pain was still obvious, so she underwent an intra-articular puncture, fluid extraction, and 1 mL of Diprospan injection into the intra-articular cavity for anti-inflammatory treatment. The pathological results of lip mucosa came back and showed that no lymphocyte aggregation was found. Till then, the diagnosis of Sjogren's syndrome was completely excluded. And the patient's joint pain relived. One week later, a re-examination of chest CT scanning showed that the inflammation of both lungs was smaller, but lymphadenopathies were basically the same as compared to before (Figure 2C and D). After consultation from the respiratory department, a transfer was recommended to clarify the nature of lymphadenopathy. Doppler ultrasonography of superficial lymph nodes detected several enlarged lymph nodes on the right clavicle, with clear boundaries, and the largest one was about 1.6 x 0.7cm. On the eighth day, the patient underwent a bronchoscopy plus endobronchial ultrasound-transbronchial needle aspiration (EBUS-TBNA) operation under general anesthesia. During the operation, a small amount of purulent secretion was found in the patient's trachea and bilateral main bronchus, which was lavaged, washed out, and sent to culture. The lavage fluid in the lower left lobe was sent for exfoliative cytology and Xpert MTB/RIF detection. Microscopically, it can be seen that the bilateral bronchial mucosa of each leaf and segment of this patient was normal, the lumen was unobstructed. And no neoplasm, bleeding, or necrosis tissues were found. Then, the ultrasonic bronchoscope was replaced. EBUS-TBNA exploration showed that the lymph nodes in group N4, N7, R10, and L11 were swollen and fused. The lymph nodes in groups N4, N7, R10, and L11 were punctured with 21G puncture needles for 1, 3, 2, and 3 times, respectively. Necrotic chips and strip tissues were extracted and sent to exfoliated cytology, tNGS and pathological biopsy detection. The whole operation process was smooth. The results of exfoliated cytology showed a few lymphocytes and neutrophils (Figure 3B-E). Pathologist reported squeezed lymphocytes and a few epithelial-like cells (Figure 3F and G). Immunohistochemistry analysis was CK (-), Vim (+), Ki-67 (+) 1%, CEA nidus (+), CK7 (-), and anti-acid staining (-). Xpert MTB/RIF was negative. However, tNGS reported 1225 reads of Legionella pneumophila in the samples of lymph node (Supplementary Table 3). Soon a multidisciplinary team (MDT) including experts in hematology, pathology, rheumatism immunity, respiration, and infection discussed the exact cause of this young lady's hospitalization. Finally, with all the information collected, especially the tNGS results, agreement was made that the patient's condition can be rationally explained by the infection of Legionella pneumophila. Thus, levofloxacin continued. By the 15th day, joint pain of the patient was completely relieved, so she was discharged from the hospital with the advice of another week's oral levofloxacin taking. A month later, not only did the interstitial changes in both lungs were further improved by re-examination of chest CT scanning, but also the enlarged lymph nodes began to shrink (Figure 2E and F). On the 59th day, the patient was followed up at the outpatient department. The symptoms of joint pain did not recur, the interstitial changes of both lungs on chest CT were further improved, and the enlarged lymph nodes were further reduced (Figure 2G and H). During the last follow-up of 141th day, the joint pain still did not recur. The interstitial lesions in both lungs disappeared completely on chest CT, and the enlarged lymph nodes became much smaller (Figure 2I and J).

legionella pneumophila, case report, levofloxacin, precision treatment, tngs, targeted next-generation sequencing

Enhanced chest CT scanning of the patient. Chest CT enhancement showed pneumonia of right lower lung disappeared under pulmonary window, and.

PMC10332418_01

Female

A 34-year-old young lady was admitted to the Department of Rheumatology and Immunology of the 2nd affiliated hospital of Chongqing Medical University (CQMU), Chongqing, China, on May 6, 2021, due to "limb joint pain for more than one month" (Figure 1). More than a month before admission, the patient developed bilateral symmetrical pains in her wrists, elbows, knees, and ankles without obvious causes, along with tenderness. These symptoms were heavier in the morning with stiffness, and slight relieving at afternoon. The involved joints were intermittent swelling, without wandering or joint deformity. During the course of disease, she had no fever, cough, expectoration, abdominal pain, and diarrhea. This lady was with a height of 160cm, and a weight of 55kg (BMI 21.48kg/m2). She was a salesperson, working at a supermarket with central air conditioning. And a dog was raised at the lady's home. She had married without a child. She had no history of smoking or alcohol consumption. There was an allergic history to cephalosporin about 10 years ago. She was born and living in Chongqing for a long time, and she had not gone to other places for a recent year. Physical examination of her whole body showed no abnormal findings. After admission, firstly, the lady's anti-Ro antibody was positive (++), Sjogren's syndrome was suspected. However, no abnormality was found in the parotid gland and bilateral submandibular glands. Therefore, lip mucosa biopsy was performed to further exclude the diagnosis of Sjogren's syndrome. At the same time, ultrasonography of muscle and bone showed that there was some effusion in the joint cavity of the right knee joint. Along with the symptoms of joint pain, rheumatoid arthritis should be considered. Next day, the negative results of anti-cyclic citrullinated peptide (CCP) and rheumatoid factor (RF) helped decrease the possibility of rheumatoid arthritis' diagnosis. Enhanced CT scanning of chest (Figure 2) unexpectedly showed bilateral pulmonary interstitial inflammation, with multiple lymphadenopathies, thus pneumonia was considered (Figure 2A and B). Although the patient had no typical symptoms like fever, cough, expectoration, or shortness of breath, levofloxacin was given empirically with elevated neutrophils (Figure 3A). At the same time, the relevant etiological examination was further arranged; however, these results were successively showed negative (Supplementary Table 2). On the third day, the lady's joint pain was still obvious, so she underwent an intra-articular puncture, fluid extraction, and 1 mL of Diprospan injection into the intra-articular cavity for anti-inflammatory treatment. The pathological results of lip mucosa came back and showed that no lymphocyte aggregation was found. Till then, the diagnosis of Sjogren's syndrome was completely excluded. And the patient's joint pain relived. One week later, a re-examination of chest CT scanning showed that the inflammation of both lungs was smaller, but lymphadenopathies were basically the same as compared to before (Figure 2C and D). After consultation from the respiratory department, a transfer was recommended to clarify the nature of lymphadenopathy. Doppler ultrasonography of superficial lymph nodes detected several enlarged lymph nodes on the right clavicle, with clear boundaries, and the largest one was about 1.6 x 0.7cm. On the eighth day, the patient underwent a bronchoscopy plus endobronchial ultrasound-transbronchial needle aspiration (EBUS-TBNA) operation under general anesthesia. During the operation, a small amount of purulent secretion was found in the patient's trachea and bilateral main bronchus, which was lavaged, washed out, and sent to culture. The lavage fluid in the lower left lobe was sent for exfoliative cytology and Xpert MTB/RIF detection. Microscopically, it can be seen that the bilateral bronchial mucosa of each leaf and segment of this patient was normal, the lumen was unobstructed. And no neoplasm, bleeding, or necrosis tissues were found. Then, the ultrasonic bronchoscope was replaced. EBUS-TBNA exploration showed that the lymph nodes in group N4, N7, R10, and L11 were swollen and fused. The lymph nodes in groups N4, N7, R10, and L11 were punctured with 21G puncture needles for 1, 3, 2, and 3 times, respectively. Necrotic chips and strip tissues were extracted and sent to exfoliated cytology, tNGS and pathological biopsy detection. The whole operation process was smooth. The results of exfoliated cytology showed a few lymphocytes and neutrophils (Figure 3B-E). Pathologist reported squeezed lymphocytes and a few epithelial-like cells (Figure 3F and G). Immunohistochemistry analysis was CK (-), Vim (+), Ki-67 (+) 1%, CEA nidus (+), CK7 (-), and anti-acid staining (-). Xpert MTB/RIF was negative. However, tNGS reported 1225 reads of Legionella pneumophila in the samples of lymph node (Supplementary Table 3). Soon a multidisciplinary team (MDT) including experts in hematology, pathology, rheumatism immunity, respiration, and infection discussed the exact cause of this young lady's hospitalization. Finally, with all the information collected, especially the tNGS results, agreement was made that the patient's condition can be rationally explained by the infection of Legionella pneumophila. Thus, levofloxacin continued. By the 15th day, joint pain of the patient was completely relieved, so she was discharged from the hospital with the advice of another week's oral levofloxacin taking. A month later, not only did the interstitial changes in both lungs were further improved by re-examination of chest CT scanning, but also the enlarged lymph nodes began to shrink (Figure 2E and F). On the 59th day, the patient was followed up at the outpatient department. The symptoms of joint pain did not recur, the interstitial changes of both lungs on chest CT were further improved, and the enlarged lymph nodes were further reduced (Figure 2G and H). During the last follow-up of 141th day, the joint pain still did not recur. The interstitial lesions in both lungs disappeared completely on chest CT, and the enlarged lymph nodes became much smaller (Figure 2I and J).

legionella pneumophila, case report, levofloxacin, precision treatment, tngs, targeted next-generation sequencing

Enhanced chest CT scanning of the patient. mediastinal lymphadenopathy were getting much smaller under mediastinal window. on the follow-up of 141th days. (Red arrow: interstitial pneumonia, blue arrow: mediastinal lymphadenopathy).

PMC8411612_01

Female

A 60-years-old female was admitted with signs of posthepatic jaundice and coagulopathy: total bilirubin (TB) : 538.7 mumol/L, direct bilirubin (DB) : 412.1 mumol/L. Coagulation test showed fibrinogen level at 110 mg/dl (normal range 180-350 mg/dl), prothrombin Quick value : 46% (normal range 0.85-1.2), international normalized ratio (INR) : 2.4 (normal range 0.85-1.2), indicating high risk of bleeding. A diagnosis of Klatskin tumor of the left hepatic duct (type 3B by Bismuth-Corlette classification) was established based on a contrast-enhanced CT scan and biopsy. The CT scan analyses revealed the tumor to be intimately adherent to the common hepatic artery (highly suspicious for invasion) as well as wrapped around the half of the portal vein. The resection of the liver with major vessels was not performed because such operation is not covered by the Medical Guarantees Package from the National Health Service of Ukraine due to poor financing of healthcare in Ukraine, and the patient was not able to cover such expenses by herself. The malignancy was diagnosed as an unresectable tumor; therefore, a palliative minimally invasive approach was chosen. The study was approved by the local ethical committee at Bogomolets National Medical University. The patient provided written informed consent to participate in the study. All data generated or analyzed during this study are included in this published article. Initially, we thought that percutaneous transhepatic biliary drainage might be favorable compared to the endoscopic approach. However, the decision was made to performed an endoscopic approach because the patient had a Klatskin tumor with a spread into the left hepatic duct, whereas the right hepatic duct was dilated and free from tumor, indicating a good prognosis for endoscopic management in this particular case. The dilation of the right hepatic duct was due to obstruction at the level of bile duct confluence. Also, a high risk of bleeding was taken into consideration, and a decision was made to perform endoscopic retrograde cholangiopancreatography (ERCP) followed by endoscopic sphincterotomy and endobiliary stenting. Application of self-expanding metal stents (SEMS) is associated with better clinical outcomes and enhanced biliary decompression. As compared to plastic stents, SEMS have a wider diameter, which is resulted in enhanced bile flow after the stent insertion. In such a condition, biliary decompression is rapid, and the risk of liver failure is increased according to Khoronko et al and our clinical observations (unpublished data). Hence, we decided to use a plastic stent in order to achieve gradual decompression because of signs of liver failure due to posthepatic jaundice. The polyvinyl chloride (PVC) stent (10 Fr, 150 mm) was placed into the right hepatic duct (Figure 1) and colorless "white" bile was received. The selective stenting of the right hepatic duct was achieved by maneuvering the flexible part of the endoscope and its elevator as well as using guidewires with J-tip, fixed, and moveable core. Also, a significant decrease in bilirubin levels was achieved. In 2.5 months after the PVC insertion, the patient was diagnosed with posthepatic jaundice and cholangitis: TB : 120.6 mumol/L, DB : 86.3 mumol/L, WBC : 12.7 x 109/L, band neutrophils (BN) : 18%, erythrocyte sedimentation rate (ESR) : 29 mm/hour. Occlusion of the PVC stent was established by MRI, followed by ERCP (Figure 2), and replacement of the stent was performed with a larger diameter (11.5 Fr, 130 mm). The patient was administrated chemotherapy with 3 g of capecitabin (18 courses). Two months later after the endobiliary restenting procedure, the patient reported fever up to 38 C and dry cough with a sudden onset. According to the patient, she had an active lifestyle, doing regular chores like farming and gardening in the countryside. During the next 7 days after the initial presentation, the dry cough was changed to a wet one with an admixture of bile, indicating biliptysis. The blood test showed WBC : 10.5 x 109/L, ESR : 66 mm/hour, TB : 12 mumol/L. CT scan showed the proximal migration of the endobiliary stent with penetration through the liver, the right dome of the diaphragm, and right lung (Figure 3). The distal part of the stent was at the level of the common hepatic duct (Figure 3C and D). The patient was not able to receive immediate endoscopic management, because such a clinical facility was not available in the area of her residence, and transportation to a tertiary referral center was not possible because of patient's fear to get infected with COVID-19. In such circumstances, conservative therapy was started by administration of Meloxicam 15 mg/day, Amoxicillin 1.5 g/day, Ceftazidim 3 g/day, and Furosemide 40 mg/day. The normalization of body temperature and blood parameters as well as the absence of biliptysis were reported in 2 weeks. During the follow-up of 9 months, there were detected neither signs of BBF nor posthepatic jaundice. MRI investigation showed signs of fibrotic tissue around the part of the endobiliary stent in the pulmonary parenchyma with a clear demarcation from the normal lung tissue (Figure 4). As the epidemic situation with COVID-19 became better, the patient arrived at a tertiary center for endoscopic treatment in Kyiv (National Military Medical Clinical Center of Ministry of Defense of Ukraine). To remove the proximally migrated endobiliary stent we visualized its proximal tip by ERCP in the common bile duct at the level of the cystic duct. Then, the tip was captured with 4 wire Dormia basket followed by its removal. The removed stent was replaced with a PVC stent (10 Fr, 150 mm) by ERCP (Figure 5). The surgical team considered possible technical problems and complications associated with fibrosis around the migrated stent, and conversion to open surgery was considered in case of unsuccessful endoscopic management. Complications were not observed at follow-up.

ercp, hilar cholangiocarcinoma, klatskin tumor, biliary-bronchial fistula, endobiliary stent, endoscopic retrograde cholangiopancreatography, non-operative treatment, proximal migration of stent

PMC3964166_01

Unknown

A total of 81 spinal arachnoid cyst patients (male:female 34:47, mean age 32 years) undergoing surgery in Beijing Tiantan Hospital from January 1995 to December 2010 were retrospectively studied. The study protocol was approved by the Ethics Committee of Beijing Tiantan Hospital. Written informed consent was obtained from all patients or from guardians for patients less than 18 years old. Inclusion criteria were: 1) diagnosis of idiopathic or congenital spinal arachnoid cyst based on MRI and clinical features, using the diagnostic criteria provided by Hughes et al; 2) aged 6-70 years at the time of treatment; and 3) conservative-treatment failure, and patient still exhibiting a baseline preoperative Fugl-Meyer (FM) score of <50 after conservative treatment. Exclusion criteria were: 1) diagnosis of another disease requiring clinical intervention or impairing routine operative care, including spinal tuberculosis or tumor; 2) undergoing treatment for diabetes mellitus or other chronic diseases; or 3) had been diagnosed with arachnoid cysts secondary to trauma, including hemorrhage, inflammation, surgery, or lumbar puncture. All patients underwent routine MRI examinations. Spinal arachnoid cysts were identified based on apparent low-signal regions in T1-weighted images. Similarly, high signals were used to indicate cerebrospinal fluid without enhancement in T2-weighted images. All examinations were conducted in accordance with previously published guidelines. Both anatomical location and abnormalities observed by MRI were assessed for each patient. Surgical procedure of spinal arachnoid cysts was determined before the year 1995 in our department. Spinal arachnoid cysts were subdivided into five types: 1) intramedullary cysts/syrinxes, 2) subdural extramedullary, 3) subdural/epidural, 4) intraspinal epidural, or 5) intraspinal/extraspinal (Figure 1). If surgical observation was inconsistent with preoperative evaluation by MRI, the surgical procedure was modified according to intraoperative observations. Surgical treatment was selected based on spinal arachnoid cyst type and conducted by a team of two trained surgeons and two assistants. All surgeries were conducted at the same facility. The use of total or partial resection was recorded for each patient. For patients with this kind of cyst, experimental puncture was performed to identify the location of the cysts, then an incision along the posterior median sulcus was made to achieve cyst opening (the length of the incision varied according to the size of the cyst). For some patients with dense adhesion between the cyst wall and spinal cord, the separation of the cyst was not continued if it was very difficult to separate. On the contrary, the clinicians removed the parts that could be separated or sutured the pia mater to the cyst wall and ensured the connection of the cyst cavity and the subarachnoid space to prevent the recurrence of the cyst. Subdural extramedullary spinal arachnoid cysts feature abnormal thickening and adhesion of the arachnoid caused by congenital aplasia and/or inflammatory responses. These abnormalities are commonly found at the ventral and ventrolateral spinal cord. Posterior shifting of the spinal cord is generally found in patients with cysts at the ventral and ventrolateral spinal cord, and thickening and adhesion of the arachnoid that could lead to dense adhesion between the spinal cord and the endorrhachis. Thus the incision of the endorrhachis should be carefully performed with the assistance of endoscopy to avoid injuries to the spinal cord. The long-term pressure on the spinal cord could result in the adhesion and thickening of the adjacent arachnoid and poor spinal cord pulsation. Thus the adhesive arachnoid between the spinal cord and the adjacent endorrhachis was separated carefully and removed as much as possible to release the spinal cord. However, the operational view of the surgical procedures on the cysts at the ventral spinal cord is generally limited, and traction of the spinal cord should be avoided as much as possible to avoid damage to the spinal cord nerves and adjacent vessels. Subdural/epidural cysts were treated by resection of the cyst wall. If no dense adhesion between the cyst wall and the endorrhachis or nerve root was found, the cyst was separated until the neck of the cyst, and then tight suturing was performed after resection of the cyst. In contrast, if dense adhesion between the cyst wall and nerve root made the separation of the cyst very difficult, partial removal of the cyst was performed, and then tight suturing was performed after the connecting hole had been filled with a section of free muscle mass. For cysts not connected with the subarachnoid space, the cyst wall was removed as much as possible. In cases of dense adhesion between nerve root and the cyst, the cyst wall was partially resected for drainage and decompression before tight overlapping suturing. A section of free muscle mass was then positioned on the dura at the site of the cyst and fixed by suture and inward pressure to prevent new cyst formation. Intraspinal epidural cysts were treated by ligation of the cervix. In some cases, the muscle mass was isolated and used to plug the access hole prior to suturing of the cyst walls. If the nerve root or dural adhesion was weak, the cyst was mobilized to the neck, resected, and sutured tightly. However, in cases of very strong nerve root or dural adhesion the cyst wall was partially resected and a piece of free muscle mass was used to plug the access hole prior to tight suturing. Intraspinal and extraspinal cysts were removed through enlarged intervertebral foramina. Extraspinal cysts are easy to be treated. Operation of intraspinal cysts is similar to subdural/epidural cysts. If no dense adhesion between the cyst wall and the endorrhachis or nerve root was found, the cyst was separated until the neck of the cyst, and then tight suturing was performed after resection of the cyst. If dense adhesion between the cyst wall and nerve root made the separation of the cyst difficult, partial removal of the cyst was performed, and then tight suturing was performed with a section of free muscle mass. For cysts not connected with the subarachnoid space, the cyst wall was removed. All patients were followed up, with a mean period of 69 months (range 3-187 months). Cases of recurrence, death, or second surgery were recorded. FM scores were assessed preoperatively and at postoperative day 90 on a 0- to 99-point scale. As previously described, FM scores were assessed as severe or marked motor impairment (0-84), moderate motor impairment (85-95 points), and slight motor impairment (96-99 points). Preoperative FM scores of all patients were less than 50 points after conservative therapy. Significant improvement was determined when postoperative FM score achieved 96-99, and clinical symptoms disappeared with incident pain or numbness; patients had a normal life and work. Improvement was determined when postoperative FM score achieved 85-95, and parts of symptoms disappeared but some moderate motor impairment still remained. No improvement was determined when postoperative FM score remained 0-84.

classification, epidural, extramedullary, intramedullary, spinal arachnoid cyst, spinal surgery, subdural

PMC6488495_01

Female

A 48-year-old woman with a medical history of biopsy-proven oral LP diagnosed 5 years earlier was presented for an evaluation of progressively increasing dysphagia for solid foods for the past 6 months. She did not have typical heartburn or regurgitation symptoms consistent with reflux disease. There was no history of corrosive injury or radiation to esophagus. She was on prednisone 5 mg/day, omeprazole 20 mg/day, and azathioprine 50 mg/day and there was not any active lesion at buccal mucosa at the time of the last visit. Esophagogastroduodenoscopy (EGD) was performed, which showed proximal esophageal benign appearing stricture 20 cm from the incisors (figure 1). There was peeling of the mucosa away from the esophagus leaving a friable, inflamed surface that bled easily on contact. Since the scope could not be negotiated distally, a pediatric scope was used. It was a short segment stricture and distal gastrointestinal (GI) tract was normal. The endoscopic and clinical findings were consistent with ELP, therefore esophageal biopsy sample was not taken. Due to the severity of the symptoms, the patient underwent three sessions of wire-guided bougie dilation up to 39 Fr. (figure 2) and her symptoms improved.

dysphagia, esophageal stricture, lichen planus

PMC9356796_01

Male

On December 30th, 2020, a sixty-seven-year-old Caucasian male, with no medical or surgical history, presented to our emergency COVID-19 department with persistent dyspnea at rest, along with chest pain, and a persistent cough initially dry becoming productive fifteen days before admission, showing no improvement on clavulanic acid-amoxicillin taken by the patient on self-medication, in a context of fever and night sweats, and deterioration of general status including a weight loss of 10 kg, fatigue, and anorexia. However, the patient had not shown any signs of otorhinopharyngeal viral infection (no anosmia, no taste alteration, no sore throat, and no rhinitis) and had not reported any known close contact with a COVID-19 except that his son had been treated for pulmonary TB infection a year earlier. Upon his admission, physical examination revealed a conscient bedridden patient, febrile at 38 C, tachypneic at 30 cpm, saturation levels at 86% on ambient air, tachycardic at 100 bpm, and normotensive with bilateral rhonchi, a swollen painful left leg with positive Homans' sign and vesicular eruption on his abdomen. On another note, his admission's capillary blood glucose was as high as 4 g/l and his urine strip revealed 2 positives for ketones and 2 positives for glucose, thus revealing an inaugural diabetic ketosis. His EKG and cardiac enzymes were normal. His laboratory findings showed an elevated white blood cells count (10240/ml) (normal: 7000-10000/ml) with high neutrophilic count, a microcytic hypochromic anemia at 10.7 (normal: 13-18 mg/dl), lymphocytopenia at 710 (normal: 1500-4000/mL), an elevated C-reactive protein at 208 (normal:<5 mg/l), normal procalcitonin level 0.26 (normal <5), elevated lactate dehydrogenase at 371 (normal: 135-225 U/L), elevated ferritin at 764 ng/ml (normal: 30-400 ng/ml), blood sugar at 2.29 g/l, and bicarbonates at 22.75 (normal: 22-30). His renal and liver full workup was normal. HIV and other viral serologies also came back negative. His chest computed tomography (CT) scan showed foci of pulmonary consolidation with diffused ground-glass opacities and multiple bilateral nodules and micronodules all in favor of a CO-RADS 5 with signs of active tuberculosis (Figure 1). His nasopharyngeal swab for COVID-19 reverse transcriptase-polymerase chain reaction (RT-PCR) came back positive, thus confirming a COVID-19 infection. Also, his sputum for MTB PCR was positive with no rifampicin resistance detected revealing a concomitant infection with Mycobacterium tuberculosis. A venous doppler ultrasound of his left leg revealed a total thrombosis of the superficial femoral, popliteal, and sural veins. The patient was admitted to one of our COVID-19 isolation units and was put under oxygenotherapy via a high flow nasal cannula at 6 liters/min. He was started on broad spectrum antibiotics (2 g of ceftriaxone) for 10 days, corticosteroids (methylprednisolone) 80 mg for 5 days, 40 mg of prednisolone orally, a fixed dose-combination of antituberculosis treatment (isoniazid + rifampicin + pyrazinamide + ethambutol), and anticoagulation with low-molecular weight heparin enoxaparin at 0.6 IU*2 per day and was prescribed support stockings. Intravenous hydration was started as per ketosis correction protocol with correction of hydroelectrolytic disorders and intravenous and then subcutaneous insulin therapy with the following regimen: basal insulin in the evening with boluses of rapid insulin three times a day, depending on the patient's capillary blood sugar. The evolution was favorable with apyrexia on the second day of treatment, the oxygenotherapy was discontinued progressively over 10 days, the patient's COVID-19 PCR came back negative on day 15th of his admission, and his chest CT scan showed endoluminal defects of the segmental arteries of the left pulmonary base, focal cystic dilatation of the upper right lobe with focal parenchymatous consolidation, multiples bilateral micronodules, and lymphadenopathy in Barety's compartment all in favor of a pulmonary embolism with signs of active tuberculosis (Figure 2). After a stay of 23 days, the patient was discharged with a prescription of anti-TB therapy, antivitamin K (started on day 15th of admission), and oral corticosteroids (prednisone) for 10 days with progressive degression and a basal bolus insulin regimen.

PMC4731900_01

Female

A 20-year-old woman was admitted to her local hospital in June, 2010 because of cough and expectoration for 3 months. She was diagnosed as tracheal tuberculosis according to the positive acid-fast bacilli in her sputum and granuloma-like lesions on the tracheal wall with caseous necrosis by bronchoscopy with biopsy. She was given anti-TB medications consisting of Isoniazid (INH), Rifampicin (RFP), Ethambutol (EMB) and Pyrazinamide (PZA). However, her symptoms were not relieved, but deteriorated after 1 month. The bronchoscopy was performed again, revealing tracheal scar stenosis. The biopsy showed chronic inflammation of the upper tracheal mucosa with fibrous tissue proliferation. She was admitted to our hospital on December 9, 2010 for further treatment. On admission, physical examinations showed that she was clear-minded, breath was 25 times per min, pulse was 93 beats per min, and blood pressure was 126/78 mmHg. On chest examination, her breath sound was rough with wheeze on both sides. The result of abdominal examination was normal. Pulmonary function testing (PFT) showed that her pulmonary function was impaired [vital capacity (VC) =3.29 L (91.9 % pred), the forced expired volume in 1 s (FEV1) =1.11 L (35.2 % pred), the ratio between FEV1 and the forced vital capacity (FEV1/FVC) =33.65 %]. A chest computed tomography (CT; Fig. 1) revealed tracheal stenosis at the thoracic inlet, patchy, nodule-like and streaking lesions with uneven density in both lobes of the lung, and normal lymph node sat mediastinum and lung hilus. After admission, she continued to receive anti-TB drugs (INH, RFP, EMB and PZA), and then changed to anti-TB drugs [INH, RFP, EMB and streptomycin(SM)] due to liver injury. Electronic bronchoscopy was performed at 3 days after admission (December, 13) under general anesthesia. Mechanical ventilation was used to assist her breathing. The bronchoscopy showed a ring-like scar stenosis about 2 cm below the normal glottis. The bronchoscope (BF BC-260, Olympus Corporation, Tokyo, Japan) with an external diameter of4.9 mmcould pass through the stenosis, but not the bronchoscope (BF IT-260, Olympus Corporation, Tokyo, Japan) with the outer diameter of 5.9 mm. The bronchoscopy (BF BC-260) revealed that the airway wall was rough, the narrowed airway was about 5 cm in length, and the lower end of the stenosis was about 5 cm away from the sharp tracheal carina. No abnormality in the bilateral lobar bronchus was observed. The tracheal stenosis was treated using the MK58880balloon (1 cm in diameter, Boston Scientific Cork Company, Ireland) with the pressure increased to 303.9 Kpa (3 atm) to dilate the trachea for 10s during which the mechanical ventilation was stopped. Subsequently, the pressure started to decrease and the mechanical ventilation was recovered. The balloon dilatation was repeated 3 times. The bronchial lumen expanded only slightly following the procedure (Fig. 2a, b). On the second day of the balloon dilatation, her symptoms including coughing, shortness of breath, were alleviated. The wheeze and stridor of lungs were reduced under physical examination. Ten days later, she received bronchoscopic re-examination of the airways and the results still indicated that the bronchoscope (BF BC-260, Olympus Corporation, Tokyo, Japan) could pass through the stenosis, but not the bronchoscope (BF IT-260, Olympus Corporation, Tokyo, Japan). Thus, the high-pressure balloon dilatation treatment was performed again during which the pressure of the balloon was increased to 5 atm and then maintained for 10 s. After 8 inflation cycles, the bronchoscope (BF IT-260, Olympus Corporation, Tokyo, Japan) can pass through the stenosis. However, her cough and shortness of breath symptoms were deteriorated following the treatment, which may be caused by the presence of bronchial edema and spasm. These symptoms were resolved by intravenous and intranasal administration of dexamethasone using atomization device. On the third day after treatment, her cough and shortness of breath symptoms were apparently ameliorated. The physical examinations showed that wheeze and stridor of lungs were remarkably reduced. Then, she was discharged. Fifty days after the treatment, a repeat PFT showed that her pulmonary function was remarkably improved (VC = 3.40 L (94.8 % pred), FEV1 = 2.06 L (65.5 % pred), FEV1/FVC = 60.51 %). A repeat bronchoscopy showed that the ring-like scar stenosis was dilated, allowing the passage of bronchoscopy (BF IT-260, Olympus Corporation, Tokyo, Japan) (Fig. 2c). During her 1 year outpatient follow-up, no tracheal stenosis was observed. Timeline of past history of the patient was listed in Table 1.

PMC4731900_02

Female

A 39-year-old female patient was admitted to our hospital on October 13, 2010 because of cough and expectoration for 3 years, chest tightness and shortness of breath for approximately 1 month. On November, 2007, she was ever admitted to a local hospital with complaints of cough, expectoration and white phlegm, but not fatigue, night sweats, fever and chest pain. The local hospital diagnosis was bronchial asthma. She was given anti-inflammatory drugs, but her symptoms persisted. On admission, physical examinations revealed that she was clear-minded, breath was 26 times per min, pulse was 100 beats per min, and blood pressure was 132/80 mmHg. Chest examination revealed wheeze in the trachea, and rough breath sound with in aspiratory and expiratory wheeze in both lungs. Her abdominal examination was normal. No pathological syndrome was observed. Chest CT scan revealed pulmonary TB on both sides, especially in the middle and lower lobe. Lower tracheal stenosis, right bronchus stenosis and right pleural thickening were also observed (Fig. 3). Sputum smear for acid-fast bacilli was positive. Subsequently she was given combined anti-TB treatment (INH, RFP, EMB and PZA) since December 13, 2010. On December 17, 2010, bronchoscopy was performed under local anesthesia, revealing that as shown in Fig. 4a, the glottis was normal, false diverticula was present in the middle segment of trachea, and stenosis was present in the middle and lower trachea, barely allowing the passage of the bronchoscopy (BF BC-260, Olympus Corporation, Tokyo, Japan). Tracheal mucosal congestion and swelling were present, and the left main bronchus and lobar bronchus on the left side was patent, although with the presence of viscous secretions. However, the right main bronchial stenosis was observed with caseous necrotic material attached to the bronchial orifice and could not permit the passage of the bronchoscopy (BF BC-260, Olympus Corporation, Tokyo, Japan). Our final diagnosis was active secondary pulmonary tuberculosis, tracheal and right main bronchial tuberculosis. On January 12, 2011, the patient was administrated with endotracheal intubation. After a month, the endotracheal catheter was removed and then, the patient was discharged. On February18, 2011, she was re-admitted to our hospital. The bronchoscopic high-pressure (6 atm) balloon dilatation (MK58880, Boston Scientific Cork Company, Ireland) was performed in the middle and lower trachea for the patient under general anesthesia and electrocardiogram (ECG) monitoring. Mechanical ventilation was applied to assist the patient's breathing. When the oxygen saturation was below 95 %, the balloon stopped dilatation and started empting. The balloon dilatation lasted as long as 1.5 min for each cycle. When the oxygen saturation recovered to be above 99 %, the second balloon dilatation was performed and repeated. The bronchoscopic high-pressure (5 atm) balloon dilatation was also performed under ECG monitoring for the right main bronchial stenosis twice with5 min for each cycle. After the balloon dilatation, the BC-260bronchoscope could pass through the middle and lower trachea stenosis but not the IT-260bronchoscope. For the right main bronchus stenosis, BC-260 bronchoscope could not even pass (Fig. 4b). Her chest tightness, shortness of breath symptoms were improved after the balloon dilatation treatment, but still could not tolerate PFT. She received balloon dilatation treatment for 5 more times on March 28, April 22, May 6, June 7 and July 18, 2011, respectively. On June 28, 2012, a repeat bronchoscopy showed that the middle and lower trachea stenosis was dilated and patent without the presence of congestion and swelling, allowing the passage of the IT-260 bronchoscope. The orifice of the right main bronchus was still narrowed, could not permit the passage of the bronchoscopy (BC-260), but the caseous necrotic materials disappeared (Fig. 4c). No restenosis occurred in the patient in 1 year outpatient follow-up. Timeline of case 2 was listed in Table 2. We searched the WANFANG and PubMed database for articles published between 1984 and 2014 in the Chinese-and English-language literature. There were several studies on the application of balloon dilatation in management of combination of main bronchus and lobe bronchus stenosis, yet rare reports on specific treatment of TB-associated tracheal stenosis by BBD were retrieved. The search of PubMed database yielded 13 articles. A total of 474 patients were involved in the retrieved articles from PubMed database and the present study. The total information retrieved was summarized in Table 3. Of the 474 patients, the tracheal stenosis of 4 infant patients results from endotracheal intubation. The etiologies of the 474 patients include bronchial carcinoma, other malignancy, lung carcinoma post-tracheal resection, endotracheal intubation, tracheal tuberculosis, prolonged mechanical ventilation, lung transplantation, Wegener's granulomatosis, idiopathic stenosis, post-tracheostomy, sarcoidosis and amyloidosis.

A chest computed tomography scan showing tracheal stenosis and right bronchial stenosis of the patient in Case 2.

PMC7683224_01

Female

Twenty-two years old female presented with a complaint of intermittent productive cough with bloody sputum of 3 weeks' duration associated with wheezing, low grade intermittent fever and loss of appetite. She had frequent similar complaints for the last 10 years for which she visited different hospitals and was given salbutamol puff and antibiotics for the diagnosis of bronchial asthma with acute exacerbation. She had no contact history with known pulmonary tuberculosis patients and have never smoked cigarettes. she has no history of drug allergy, self or family history of relevant medical or surgical illness. On presentation her vital signs were in the normal range. She had scattered wheeze over her right posterior lower third lung field. Otherwise, there was no remarkable finding on other systems evaluation. Her complete blood count, renal function test and serum electrolytes were in the normal range. Chest computerized tomography (Chest CT) showed 5.6 cm x 4.4 cm enhancing, lobulated, soft tissue mass in the lower lobe of the right lung. The mass has endoluminal extension to bronchus intermedius and the lower lobe of the right lung has marked collapse due to bronchial obstruction (Fig. 1). Bronchoscopic evaluation revealed red, fleshy and fragile right bronchus intermedius mass, and tissue biopsy from the mass showed organoid growth pattern of monomorphic small cells with paper chromatin, inconspicuous nucleoli surrounded by delicate vessels with diagnostic impression of typical carcinoid tumor. Abdominal ultrasound examination didn't reveal evidence of liver secondary. With an impression of right lung lower lobe typical carcinoid tumor, the patient was operated through right posterolateral thoracotomy after getting informed written consent. The intraoperative finding was an 8 cm x 6 cm firm lower lobe mass involving bronchus intermedius (Fig. 2, Fig. 3). There were multiple enlarged mediastinal lymph nodes involving stations 8, 9 and 11. With these findings right lung bi-lobectomy (middle and lower lobe) with mediastinal lymphadenectomy of station 8, 9 and 11 was done and we left right tube thoracostomy. Post procedure, she was transferred to intensive care unit and put on oxygen support as well as epidural analgesics. Subsequently, she had smooth recovery and was transferred to surgical ward. The chest tube output was insignificant and minor bubbling decreased gradually. Control chest x ray taken on her 5th post op day showed well expanded right upper lobe with no evidence of pneumothorax for which the chest tube was removed. Histopathologic study of the excised mass showed lobulated tissue consisting of organoid and trabecular growth pattern with scattered pseudoglandular pattern. The cells are uniform round with salt and paper chromatin pattern. There was no evidence of mitosis and necrosis the final diagnosis being typical bronchopulmonary carcinoid tumor (Fig. 4, Fig. 5). The mediastinal lymph nodes were free of metastatic deposits. Subsequently, the patient showed a remarkable improvement and was discharged from the hospital in a stable condition.

carcinoid tumor, case report, endobronchial, lung cancer, typical

Chest CT scan showing enhancing, lobulated right lung lower lobe soft tissue mass encasing bronchus intermedius.

PMC5478565_01

Male

In 2014, a 76-year-old man with an approximately 26-year history of DM collapsed and was admitted to a community hospital with dehydration and a fever. His HbA1c (National Glycohemoglobin Standardization Program) level was 6.4%. The patient's mother, with whom he had lived for a long period during his youth, had once been successfully treated for pulmonary TB. Computed tomography (CT) was performed to investigate the cause of the fever and inadvertently revealed a 25-mm mass-like lesion in the pancreas head (Fig. 1). The patient was referred to our hospital for further examination. Contrast-enhanced CT revealed the lesion to be hypovascular. The lesion showed a high-intensity signal on diffusion magnetic resonance imaging (MRI) (Fig. 2). The serum levels of carcinoembryonic antigen (CEA), CA19-9, DUPAN-2, and SPAN-1 were all normal. Enlarged peripancreatic lymph nodes are often seen secondary to chronic liver diseases; however, the patient was negative for hepatitis B surface antigen, anti-hepatitis C virus antibody, and anti-HIV antibody. Gastrointestinal endoscopy and colonoscopy showed no evidence of advanced malignant tumors causing malignant lymphadenopathy. Using a 22-gauge fine-needle aspiration (FNA) needle (SonoTip(R) Pro Control; Medi-Globe GmbH, Achenmuhle, Germany), we performed endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) of the peripancreatic hypoechoic and heterogeneous lesion (Fig. 3). There were no abnormal signs, such as direct invasion or compression of the portal vein or common bile duct. Aspiration biopsy cytology via EUS-FNA was class II; a histological analysis revealed necrotic tissues without malignant cells or Langhans giant cells (Fig. 4). On positron emission tomography (PET)-CT, there were the lesions with abnormal uptake of fluorodeoxy glucose (FDG)-PET in the left supra-clavicular lymph node and the peripancreatic lesion (Fig. 5). A whole biopsy of the left supra-clavicular lymph node was performed by an otolaryngologist, and a tuberculous granuloma with caseous necrosis was found (Fig. 6). Polymerase chain reaction (PCR) showed the granulomatous tissue to be positive for TB. PCR of the peripancreatic tissue obtained via EUS-FNA was also positive for TB (Fig. 7). Based on these findings, we made a diagnosis of tuberculous lymphadenitis, which was confirmed by a positive QuantiFERON test result. A follow-up examination after a 6-month course of treatment for extrapulmonary TB showed that the peripancreatic lymph node had decreased to approximately 10 mm in size.

mycobacterium tuberculosis, endoscopic ultrasound-guided fine needle aspiration (eus-fna), peripancreatic tuberculous lymphadenitis, polymerase chain reaction (pcr), positron emission tomography (pet)-ct

PMC9751151_01

Female

A 9-month-old female presented to Hospital Central de Maputo with 3 days of cough which progressed to respiratory distress, poor oral intake, fever, lethargy, and white oral plaques. She was hypoxic with oxygen saturations of 85% on room air with tachypnea and subcostal retractions. Her admission laboratory included a full blood count with leukocytes of 18.7 x 103 cells/uL, hemoglobin of 7.3 g/dL, and platelets of 73 x 103/uL, and a biochemistry panel with normal creatinine, transaminases, and basic electrolytes. She was diagnosed with severe pneumonia, oral candidiasis, moderate anemia, and severe acute malnutrition (weight for height Z score = 0.1 percentile), admitted, and started on oxygen supplementation, intravenous antibiotics and antifungal therapy, and therapeutic milk. The mother was HIV-positive and had been on antiretroviral treatment (ART) for 7 years, but due to nausea and vomiting during the first trimester of pregnancy she stopped taking her regimen of tenofovir/lamivudine/dolutegravir and did not resume treatment after birth. She reported an uncomplicated pregnancy and vaginal delivery at 41 weeks of gestation, with APGAR scores of 8 and 9 at 1 and 5 min, respectively. The infant received post-natal prophylaxis with 6 weeks of zidovudine and 12 weeks of nevirapine treatment for prevention of mother to child transmission of HIV (PMTCT). She had a negative DNA polymerase chain reaction (PCR) test at 1 month of age and was initiated on cotrimoxazole prophylaxis. She was breastfeeding and in HIV-exposed infant follow-up care until the age of 6 months, after which time she was lost to follow-up. There were no prior hospitalizations and no known tuberculosis (TB) contacts. Given the history and clinical presentation at admission, a point-of-care HIV nucleic acid test was ordered and returned positive. With this finding, and a chest radiograph that had bilateral interstitial opacities, treatment for Pneumocystis jirovecii and cytomegalovirus were added. Her baseline HIV RNA PCR viral load was >1,000,000 copies/mL, and she had severe immune suppression with a CD4 cell count of 280 cell/mm3 and 23%. COVID-19 PCR was negative as were TB diagnostic tests including Xpert MTB/Rif (on nasopharyngeal aspirate and stool specimens) and urine lipoarabinomannan (LAM). On developmental history, the mother reported that she was initially meeting most age-specific developmental milestones until 6 months of age. She tracked objects across visual field at 2 months, had full head control at 3 months, sat with assistance at 5 months, and sat independently at 6 months. After 6 months of age, the patient started to regress with loss of development milestones, and prior to admission she could no longer sit independently and lost head control. The mother also reported progressive weakness, apathy, and decreased interactivity, but denied any focal neurologic deficits or history of seizures. On her intake neurologic examination, she was responsive but lethargic. There was significant bilateral upper extremity hypertonicity, bilateral hyperreflexia of the biceps tendons, and mild axial hypotonia. Lower extremity tone and reflexes were normal. She had right eye divergent strabismus, but no other notable cranial nerve abnormalities. The anterior fontanelle was normotensive, and there was no nuchal rigidity. Head circumference was at the 8th percentile for age (42 cm), with a decrease in growth velocity based on previous measurements documented on the infant's health card. The remainder of the neurologic examination was within normal limits without any asymmetry noted. There was no history of seizures. Supplementary examinations including neuroimaging (computerized tomography or magnetic resonance imaging) and toxoplasmosis and cytomegalovirus serologies were not available. However, based on the developmental regression and abnormal neurologic examination with pathological upper extremity reflexes and hypertonia, a clinical diagnosis of HIVE was made. She was discharged after 11 days of hospitalization with resolution of her respiratory illness and improvement in her nutritional status, but without any changes in her neurologic examination. ART was initiated on the day prior to discharge with a regimen of abacavir, lamivudine, and lopinavir/ritonavir (LPV/r). After discharge, she was referred for physical and occupational therapy, outpatient nutritional rehabilitation, and maintained monthly outpatient follow-up for her HIV, with good reported ART adherence. She had one readmission at 11 months of age for acute gastroenteritis with dehydration for 7 days. After 12 months of age and 3 months on ART, her viral load had decreased to 729 copies/mL, her weight had increased from 5.1 to 7.0 kg, with normal acute nutritional status classified by weight for length Z score, and her head circumference for age was now in the 12th percentile. Developmentally, she had improved head control, was sitting independently in tripod position, displayed more social interaction, and showed age-appropriate separation anxiety. She was able to roll-over, was babbling, and had raking grasp, but was still not crawling, standing, or walking with support. On neurologic examination, she had improved axial hypotonia, with resolution of upper extremity hypertonia. Strabismus was unchanged. At 15 months of age and 6 months on ART, she continued to gain weight and show neurodevelopmental improvement. She was now able to sit independently, stand and take a few steps with support, transfer objects between hands, and had two words that she routinely used. On examination, her axial muscular tone, appendicular muscular tone and reflexes were symmetric and intact, and her strabismus was less pronounced.

art, hiv, encephalopathy, infant

PMC7425314_01

Male

A 36-year-old male football player with no significant past medical history recently diagnosed with unprovoked deep venous thrombosis of the lower limb, presented with acute right-sided hemiplegia, hemi-sensory loss, facial upper motor neuron lesion and expressive aphasia. Prior to the presentation, the patient had a history of undocumented fever, but no reported history of chest pain, shortness of breath, weight loss, night sweating, drug abuse, alcohol consumption or family history of similar presentation. With the aid of the above information, the computed tomography (CT) of the brain showed multiple bilateral occipital and frontoparietal areas of hypodensities more on the left cerebral hemisphere. The transthoracic echocardiogram revealed left ventricular ejection fraction of 60%, the presence of masses attached to mitral and aortic valves needed to be evaluated further by tranesophageal echocardiogram (TEE). The TEE showed multiple highly mobile, irregular shape masses attached to right and left coronary cusps of the aortic valve, largest mass measuring 20 x 18 mm2 with eccentric severe aortic regurgitation, no associated abscess or fistula, similar echogenicity mass attached to anterior mitral valve measures 7 x 4 mm2, and posterior mitral valve mass measures 5 x 3 mm2, and there was mild mitral regurgitation and no intracardiac shunt (Figure 1(a) and (b)). Magnetic resonance imaging (MRI) of the brain (Figure 2(a) and (b)) revealed multifocal diffusion restrictions involving bilateral high frontal and left thalamus, bilateral occipital lobes, and bilateral cerebellar hemispheres, with no significant mass effect. Forty-eight hours of follow-up CT of the brain confirmed the presence of hemorrhagic transformation. Clinically, the patient showed improvement in the expressive aphasia and the right-sided hemiplegia during the first week of admission. The patient was clinically stable throughout his hospitalization course. The follow-up investigations of all the tests performed on the patient leads to the following conclusions: (1) all blood cultures were negative; (2) Brucella titer and serology for Q fever were negative; (3) markers for tumors came back positive (CA-125 102 U/mL, CA19-9 5247 U/mL, CEA 13.6 U/mL); (4) thrombophilic evaluation, including anti-nuclear antibody (ANA), anti-neutrophil cytoplasmic antibody (ANCA), antiphospholipid antibodies (cardiolipin IgG and IgM), Factor-V Leiden mutation, homocysteine, Protein-S, Protein-C and Antithrombin-III levels, was unremarkable; and (5) CT scan of chest, abdomen and pelvis unveiled the presence of hypovascular hepatic mass having dimensions of 7.8 x 5.7 x 6.4 cm3, which invaded the right portal vein as well as the right hepatic duct with multiple porta hepatis and retroperitoneal lymphadenopathies, thereby leading to an alarming stage of cholangiocarcinoma (Figure 3). On a similar note, the peripheral right lung showed lesion with central cavitation probably infarction or metastasis, in addition to the presence of bilateral hypodense renal cervical lesions. The patient underwent ultrasound-guided liver biopsy showed well-differentiated adeno-carcinoma, consistent with the diagnosis of cholangiocarcinoma (Figure 4(a) and (b)). The follow-up transthoracic echocardiogram after 10 days of admission showed the presence of a small calcified aortic valve mass, which measures 6 x 4 mm2, mild aortic and mitral regurgitation and no evidence of mitral valve mass (Figure 5(a) and (b)). At this stage, upon his and his family request, the patient was transferred to an oncology center in the United States, where he was recommended for palliative treatment. Unfortunately, 6 months later, the patient died.

thrombotic endocarditis, cholangiocarcinoma, endocarditis, thrombophilia

PMC5030368_01

Male

A, 67 year old male, with no previously known comorbidities presented to our hospital with fever, cough, generalized weakness and low back ache since 1month. He gave a history of receiving oral antibiotic treatment during the past month, but his symptoms did not resolve. He was febrile, had tachycardia (108 beats/min), blood pressure was normal (120/80 mm of Hg), and maintained oxygen saturation of 96% in room air. A routine random blood sugar (RBS) testing revealed very high blood glucose level (RBS- 704.2 mg/dl). He was admitted for further investigation and management. His blood sample was sent for analysis and he was started on a broad spectrum antibiotic (intravenous ceftriaxone). His blood glucose levels were controlled with insulin and oral anti-hyperglycemic agents. He was also symptomatically treated with antipyretics, bronchodilators and expectorants. Upon investigation his chest radiograph showed bilateral multiple thick walled air filled cavities [Image 1]. High resolution computed tomography (HRCT) of his lungs revealed multiple evolving thick walled cavities in both lungs suggestive of Koch's [Image 2, Image 3]. Based on the nature and duration of symptoms, relentless course, diabetic status and classical radiographic findings a clinical diagnosis of pulmonary tuberculosis was made. His sputum samples were sent for acid fast bacilli (AFB) smear and he was started on standard anti tubercular treatment (ATT) (Rifampicin 600 mg, INH 300 mg, Ethambutol 1 gm, and Pyrazinamide 1.5 gm, along with Pyridoxine). Two consecutive sputum samples (early morning and evening of the same day) did not show any AFB on smear. So the next day a further sample was sent for AFB smear, bacterial culture and sensitivity, and PCR assay (GeneXpert-MTb/Rif) for Mycobacterium tuberculosis. His blood sugars were controlled with insulin, and oral anti-hyperglycemic agents. He was also symptomatically treated with antipyretics, bronchodilators and expectorants. His renal and liver functions were evaluated and found to be normal. Meanwhile the blood counts showed an elevated total count (12,440) with relative neutrophilia (85.6%). His erythrocyte sedimentation rate (ESR) was 62 mm/hr. The sputum culture grew Escherichia coli (E. coli), resistant to most first line antibiotics including ceftriaxone. It was sensitive to gentamicin, amikacin, meropenem and piperacillin/tazobactam. The GeneXpert-Rif report was negative for Mycobacterium tuberculosis. His blood culture was sterile and no growth was noticed after 72 hours of incubation. He continued to be febrile with fever spikes (between 100 and 102 deg F). In view of the conflicting evidences the scope of investigations were broadened. A bronchoscopy was performed and bronchoalveolar lavage (BAL) fluid was obtained. The BAL fluid sample was analyzed for AFB smear and culture, gram's stain, bacterial culture & sensitivity, fungal stain and fungal culture along with study for presence of malignant cells. Ceftriaxone was stopped and he was started on piperacillin/tazobactam. The BAL sample studied did not show the presence of any AFB, fungal elements or malignant cells on smear. On bacterial culture the BAL sample grew E. coli with a colony count of 104 cfu/ml, resistant to most first line antibiotics including ceftriaxone, cefuroxime and cefixime, with in-vitro sensitivity to levofloxacin, gentamycin, amikacin, meropenem and piperacillin/tazobactam. Over the next 1 week the patient improved clinically. His cough decreased and he became afebrile. A diagnosis of necrotizing pneumonia due to E. coli was made and ATT was stopped. His blood sugars were well controlled and dose of his oral anti-hyperglycemic drugs titrated and he was discharged from the hospital. He continued to receive parenteral piperacillin/tazobactam on an out-patient basis for 10 days and he was followed up regularly. His cough steadily decreased and serial chest radiographs on follow up, over the next 4 months showed gradually resolving cavities. During follow up, the BAL culture reports were received and they did not grow any fungus and the culture was negative for AFB. The cavities completely resolved at 4 months [Image 4].

cavitating necrotizing pneumonia, cavitatory lung lesion, e coli pneumonia, thick walled cavity

PMC3523559_01

Male

A 51-year-old patient was admitted to the hospital with retrosternal pain in December 2010. In his medical history, the patient mentioned hypothyroidism and has been on L-thyroxin 150 mg/day for 13 years. The patient's medical history also revealed hypertension and mild heart failure, he had been receiving angiotensin-converting-enzyme (ACE) inhibitors (ramipril 5 mg/day) and beta blockers (bisoprolol 5 mg/day) as treatment for the past 2 years. He occasionally received a nonsteroidal anti-inflammatory drug (NSAID) for musculoskeletal pain. In order to complete the diagnostic work up, the patient underwent a coronary angiography on January 19, 2011. During the examination, just after radiographic contrast media administration, (he received 60 mL iopromide intravenous [iv]), he presented symptoms of an allergic reaction, including dyspnea, tachypnea, tachycardia, and hypoxia. In addition, his lung X-ray showed a bilateral reticular thickening, an image that agreed with a possible allergic alveolitis. The patient was treated with corticosteroids (40 mg prednisolon iv). His clinical situation promptly improved, but the X-ray findings persisted (the patient had a normal X-ray image before the examination) (Figure 1A and B). He had no prior history of allergic bronchial asthma or other allergies, and this was the first time that he received a contrast media agent. Throughout the first 15 days, the patient's X-ray findings remained abnormal and he presented with hypoxia and desaturation at room temperature (pO2 47-49 mmHg, pCO2 37-39 mmHg [FiO2 21%]). He additionally demonstrated decreased ability for exercise (6-minute walking test [6MWT] 360 m). The echocardiogram did not show significant pathologic findings (left ventricular ejection fraction 65%, interventricular septal thickness 14 mm). However, the body plethysmography was compatible with a restrictive disorder and severe diffusion disorder (TLCO 34%, KCO 61%, TLC 3.81 [55%], FEV1 1.8 L [51%], VC max 2.2l [49%]). The high resolution computed tomography (HRCT) of the lungs revealed an eosinophilic pulmonary fibrosis pattern of airspace disease and patchy peripheral ground-glass opacities (Figure 2). The cardiopulmonary exercise test confirmed a limitation of pulmonary function (Wmax 95 W [53 W, ramp 12 W/minute]; VO2 max 1614 mL/minute [63% predicted] = 17.7 mL/minute/kg; Wmax 95 W = 43% predicted; O2 pulse demonstrated a plateau at 11.4 mL/beat [67%], VE/VO2 or VE/VCO2 under maximal workload [without any further reserve]). Finally, we performed a right heart catheterization and we confirmed the history of a true diastolic dysfunction of the left ventricular (wedge pressure 18-20, pulmonary artery pressure systolic/diastolic/mean 42/20/29; cardiac output 5.9 mL/minute). The laboratory tests that were performed in order to exclude the connective tissue disorders (IgG, IgM, IgA, ANA, p- and c-ANCA, C3, C4, and ENA) throughout his hospitalization were negative. Possible infections from viruses, microbes, Chlamydia, or tuberculosis (polymerase chain reaction [PCR] negative) were also excluded. Three weeks later after all the above tests had already been performed, the patient underwent a video-assisted thoracoscopy so that we could reach a final diagnosis. The biopsy revealed a very severe fibrotic disorder throughout most of the lung (end-stage lung) (Figure 3). Histomorphologically, the lesion did not resemble some of the typical interstitial lung patterns (usual interstitial pneumonia, non-specific interstitial pneumonia, desquamative interstitial pneumonia, bronchiolitis obliterans organizing pneumonia, acute interstitial pneumonia, respiratory bronchiolitis -interstitial lung disease). At that time there was a lymphocyte-stimulating test performed with all other possible causative drugs (beta blockers, angiotensin-converting-enzyme-inhibitor), but the results were negative showing no clear immunologic trigger mechanism from the chronically taken drugs. This was a chronic interstitial pneumonitis with eosinophils and fibrosis with a honeycombing image. This process was acute and progressing very rapidly and was directly dependent on the patient's radiographic contrast media exposure. The patient was treated with corticosteroids, receiving a gradually reducing dose (from 60 mg to 25 mg). One year later, in a scheduled check-up visit, his clinical condition was improved (6MWT, lung function parameters [TLC 55% predicted, FEV1 51% predicted]) (Figure 4). Throughout the patient's evaluation period, no peripheral blood eosinophilia was observed.

interstitial lung disease, orphan disease, radiographic contrast

Axial, high resolution CT images of the lungs in a patient with eosinophilic pulmonary fibrosis demonstrate peripheral distribution of airspace disease and patchy peripheral ground-glass opacities. . Abbreviation: CT, computed tomography.

PMC6815603_01

Male

The first patient was a 48-year-old Caucasian male with progressive and unintended weight loss, daily diarrhoea (initially without bleeding), and fever. In the past medical history, he had a previous diagnosis of seronegative spondyloarthritis because of 7-year intermittent joint swelling, early morning stiffness associated with inflammatory back pain and increased C-reactive protein (CRP), and a familiar history of psoriasis. No history of travel or surgery was recorded. Therapeutic trials with different antirheumatic drugs included methotrexate, hydroxychloroquine, etanercept (ETN), and finally, tocilizumab (TCZ). The most recent medical history of the first patient was characterized by disease relapse with fever and systemic inflammation (CRP 20 mg/l) without any response to a medium dose of glucocorticoids in May 2017. Before May 2017, he was finally treated with monthly TCZ 8 mg/kg intravenously, which was effective on his clinical manifestations, allowing the resolution of arthritis, and fever and led to normalization of CRP within 3 months of therapy and, notably, lasting 2 years. In April 2017, abdominal pain, daily fever (around 38 C), and daily diarrhoea without bleeding started. The patient reported a relevant weight loss of 8 kg during the last 3 months. Importantly, physical examination showed no evidence of an arthritis flare, while cutaneous lesions on the lower limbs that may resemble a cutaneous vasculitis or atypical psoriasis. Laboratory exams revealed CRP 72 mg/l, hemoglobin 10.7 g/l, HLA-B38 positive, and HLA-B27 and B51 negative. Rheumatoid factor (RF), anticitrullinated protein antibodies (ACPAs), ANA, and ANCA autoantibodies were negative. The day after the admission in our hospital ward, the patient presented bloody diarrhoea with a significant decrease in the hemoglobin level in 24 hours (from 10.7 g/dl to 8.4 g/dl). Thus, he urgently underwent colonoscopy and gastrointestinal arteriography, but without revealing the site of bleeding. We tested also Vidal-Wright reaction, CMV, HBV, HCV, H. pylori, TB test, rotavirus, adenovirus, norovirus, Yersinia, Shigella, Salmonella, Campylobacter, Clostridium, and blood cultures, but all tests resulted negative. Suspecting an intestinal vasculitis or a chronic inflammatory bowel disease, we administered methylprednisolone 1 g daily for three days with the regression of diarrhoea and fever. In order to find the site of bleeding, he underwent a gastrointestinal bleeding scintigraphy and CT-PET, which revealed a diffuse uptake in the small bowel. Because of persistent weight loss, we introduced parenteral nutrition and explored other causes of malabsorption syndrome, such as WD; thus, the patient underwent gastroscopy. The histological findings resulted in PAS-positive granules in macrophages (intestinal lipodystrophy) (Figure 1). T. whipplei was then detected in blood, feces, and saliva samples by PCR in an international reference laboratory. Intravenous ceftriaxone (2 g daily for one week) was started followed by trimethoprim-sulfamethoxazole 160/800 mg 3 times a day with dramatic improvement. There were no relapses after 6 months and was a significant weight recovery (Figures 2 and 3).

PMC6815603_02

Male

The second patient was a 55-year-old Caucasian male, with a history of symmetric polyarthritis and systemic inflammation (CRP 130 mg/l) without fever, previously diagnosed as seronegative rheumatoid arthritis in 2012. No history of travel or surgery was recorded. Over the years, he was treated with cDMARDs (methotrexate) and bDMARDs (certolizumab, ETN, TCZ, abatacept, and adalimumab). The disease relapsed with arthritis (synovitis demonstrated by US), fever (39 C), and thoracic discomfort, suspicious for pleurisy in September 2017. Previous treatments provided only a partial clinical benefit; however, the systemic inflammation with CRP ranging from 20 to 40 mg/l persisted. There was not any improvement with the introduction of colchicine. After switching to anakinra, we even registered a clinical worsening with fever, arthritis, laterocervical lymphadenopathy, and thoracic rash along with a higher systemic inflammation (CRP 213 mg/l). Many infections were excluded (i.e., CMV, EBV, chlamydia, mycoplasma, TB, Salmonella, Shigella, and Borrelia burgdorferi) as well as autoinflammatory diseases (negative genetic tests for Mediterranean fever and no improvement with colchicine and anakinra treatment, as reported) and, initially, WD by negative duodenum histopathology (no signs of PAS-positive granules in the duodenum samples). In the absence of other diagnosis, the adult onset Still's disease appeared the most probable one. The patient was then treated with steroid 0.5 mg/kg/day, with clinical improvement. Infliximab was started and steroid progressively tapered, but with recurrence of fever and systemic inflammation (CRP 68 mg/l). Despite the PAS negativity in the duodenal biopsy, the patient was then treated with ceftriaxone, showing a dramatic and rapid clinical and laboratory improvement (Figure 4). Thus, the duodenal samples, as well as other samples from stool and saliva, collected before the introduction of the antibiotic therapy, were analyzed for T. whipplei by PCR in the Reference Center of Marseille, resulting all positive (Figures 5 and 6). Finally, the patient was treated with doxycycline 100 mg twice daily and hydroxychloroquine 6 mg/kg/day, with no relapse after 6 months.

PMC9637884_01

Male

A 37-year-old male of Filipino descent who had lived in Bakersfield, California, for three years before presentation, with a history of Lynch syndrome, glucose 6-phosphate deficiency, hypertriglyceridemia, and essential hypertension, presents with a chief complaint of a perianal lesion that had started one month prior. He described the lesion as enlarging, extending to the scrotum with a "C" shape, and associated with rectal pain with poor response to analgesics. He denied having constitutional, neurologic, pulmonary, musculoskeletal, or urinary symptoms. Before this visit, he had a colonoscopy six years prior for his Lynch syndrome without abnormal findings. He denied the use of tobacco, alcohol, or illicit drugs. He was not sexually active, identified as heterosexual, denied a history of anal intercourse, and denied any trauma to the anal and perineal areas. His travel history included going to Pennsylvania one year before the visit, and he was studying for pilot school. He denied known exposures to tuberculosis. His physical exam demonstrated vital signs within normal limits and a semicircular right firm perianal lesion extending into the perineal and scrotal area; it was erythematous, edematous, and tender to palpation. No masses on digital rectal examination (DRE) or bleeding were noted, with normal sphincter tone. The initial laboratories showed: a complete blood count, comprehensive metabolic panel, hemoglobin A1C within normal limits, and a 4th generation human immunodeficiency virus (HIV) test that was negative. During the initial visit, he was prescribed seven days of ciprofloxacin. In his follow-up visit, he reported that the mass was growing, and an MRI was performed to evaluate it in detail. A pelvic MRI with contrast showed an extensive 8.6 cm multiloculated thick-walled fluid collection (Fig. 1) within the right perineum consistent with an abscess with inflammatory changes extending towards the left peritoneum, right ischio-anal fossa, and prostate. Focal fluid collections within the prostate were suggestive of abscesses. Several small anal fissures did not appear to communicate with the fluid accumulation. After those results returned, he was scheduled for a new appointment, although due to worsening pain, he decided to come to the emergency department (approximately 3 weeks later after the initial visit), and an emergent surgery was performed. The surgery team performed an incision and drainage. The right perianal abscess cavity tracked anteriorly with induration surrounding and within the anal canal. The bacterial culture grew Klebsiella pneumoniae (susceptible to all tested antibiotics in the antibiogram, including ciprofloxacin). Pathology studies from the abscess cavity demonstrated skin and subcutaneous tissue with marked acute and chronic inflammation and reactive changes. The primary team did not order fungal stains in the tissue sample. He was discharged home on ciprofloxacin 500 mg orally twice daily and metronidazole 500 mg thrice daily. After his discharge, he started to have generalized abdominal pain and increased (3 times a day) watery bowel movements without blood or mucus; the symptoms resolved without any new medication after two weeks. Fifteen days later, fungal cultures of the drained material grew Coccidioides immitis. Coccidioides serologies resulted in a positive immunodiffusion test and complement fixation (CF) titer of > 1:4096. A chest tomography showed a right lung cluster of nodular opacities. A bone scan did not show any bone lesions; however, there was a pleural-based soft-tissue density in the medial right upper lung (16 x15 mm) adjacent to the posterior right 6th rib. Based on his clinical presentation, serologic studies, and culture results, we presumed Coccidioides infection as the source of the pulmonary, pleural, and prostatic lesions. We started fluconazole 800 mg daily for disseminated coccidioidomycosis. After the incision and drainage, the patient reported immediate improvement in the pain and sensation of fullness. During his initial follow-up, he denied any pulmonary, constitutional, urinary, or recurrent perianal symptoms while on antifungal therapy. In the physical exam, the erythema and edematous appearance of the perineal skin resolved. After starting fluconazole, he reported persistent nausea, abdominal pain, and dry oral mucosa. Due to this, the patient was changed to posaconazole delayed-release tablets 300 mg daily. After one week (and approximately three months after initial perianal abscess drainage), the patient came to the emergency department with fevers, chills, conjunctival injection, and headaches and tested positive for SARS-CoV-2. After two weeks, most of the symptoms disappeared. Although the headache persisted, it was frontal and bilateral, not associated with changes in mental status, neck pain, neck stiffness, photophobia, changes in vision, focal motor/sensory deficits, rhinorrhea, or sinus pain. CT of the head without contrast did not show any abnormalities. A lumbar puncture was performed and showed opening pressure, cell count, protein, and glucose within normal limits, with negative bacterial and fungal cultures. Serum Coccidioides complement fixation titer decreased to 1:1. One month later, the patient reported high blood pressure (170/80 mmHg) despite taking his medications appropriately. The posaconazole level was elevated (5.78 mcg/mL). We suspected posaconazole-induced pseudo hyperaldosteronism (PIPH) because of the elevated posaconazole level, hypertension, undetectable aldosterone blood levels, blood renin levels close to the inferior limit (0.6 ng/mL/hour), and potassium serum levels in the inferior border of the range (3.2 mEq/L). We decreased the dose to 200 mg PO daily and his blood pressure subsequently normalized. The patient lost to follow-up after that visit. The patient was scheduled for a follow-up pulmonary study. However, it is unclear if he will come back. If he returns to our institution, we will place the patient on 12-24 months of therapy. If his symptoms are absent and there is radiological resolution of the lesions after that interval, we would discontinue antifungal therapy and place him in a period of close observation to evaluate symptoms and CF titers. We would avoid indefinite therapy in the absence of CNS disease. If the patient requires immunosuppressive therapy or acquired/developed a cellular immunodeficiency, we will recommend secondary prophylaxis.

abscess, coccidioides, coccidioidomycosis, perianal

PMC5137637_01

Male

A 53-year-old man presented with a 3-year history of recurrent abdominal pain localised to the upper abdomen. The pain was moderate in intensity and occurred on an empty stomach. It was relieved with food intake. There was no associated nausea or vomiting. There was no history of associated co-morbidities. Since the symptoms were suggestive of APD, an oesophagogastroduodenoscopy was performed, which found an ulcer in the first part of the duodenum (Fig 1). A diagnosis of a duodenal ulcer was made and he was given two-week course of Helicobacter pylori eradication therapy with omeprazole, clarithromycin and amoxicillin. As there was no improvement in symptoms following treatment, ultrasonography of the abdomen was performed to look for other causes. This revealed pneumobilia with a 2.2cm x 1.9cm well defined hypoechoic lesion close to the proximal body of the pancreas, suggestive of a peripancreatic lymph node, and a 1cm x 0.9cm non-shadowing echogenic focus in the gallbladder, suggestive of sludge. Pneumobilia was also demonstrated on plain x-ray of the abdomen (Fig 1). An upper gastrointestinal contrast study was carried out to diagnose the aetiology, which revealed a CDF. A repeat oesophagogastroduodenoscopy was performed and the fistula was clearly made out (Fig 1). Based on these findings, a provisional diagnosis of chronic duodenal ulcer with CDF with chronic cholecystitis was considered and the patient underwent open cholecystectomy and truncal vagotomy with gastrojejunostomy. Intraoperatively, a nodule with a 1cm x 1.5cm fistulous opening was found in the duodenum, with multiple peritoneal deposits. The possibility of TB was considered. On histopathology, the gallbladder showed chronic cholecystitis with intestinal metaplasia and the peritoneal nodules revealed caseation with epitheloid granulomas suggestive of TB (Fig 2). Postoperatively, the patient was investigated for other foci of TB and retropositive status, both of which were negative. He was put on Revised National Tuberculosis Control Program category I antitubercular therapy with isoniazid, rifampicin, ethambutol and pyrazinamide for two months, followed by isoniazid and rifampicin for four months. He has been on regular follow-up for the past three years and remains asymptomatic.

PMC4374085_01

Female

The interaction of human beings with wild reindeer and the animals' grazing and trampling behaviour has shaped the northern ecosystems since the last ice age (Suominen and Olofsson:235). Nomadic Sami herding emerged in the 17th century (Nakkalajarvi:40), and was based on pasture rotation from the coastal summer lands of Norway to inland areas of Finland-Sweden or, after Finland was ceded to Russia by Sweden in 1809, Finnish Russia (the Grand Duchy of Finland under the Russian Empire). In difficult winters, marked by hard snow, thick snow or icy ground, reindeer exhibited an emerging characteristic of seeking forage outside of the normal pasture rotation. People used to say: "After a good lemming year there will be a bad year for reindeer "(M1-M13, F1-2). The reindeer "broke loose" and went into forests with a rich availability of arboreal lichens or onto fell slopes with "wind-whipped snow" (Gibson; Vuojala-Magga et al.; Turunen and Vuojala-Magga). Animal behaviour like this can be seen as a temporal act of habitat selection resulting in an enlargement of the animals' niche. However, harsh conditions increased winter mortality and/or reduced the reproductive rate of the weakest reindeer; in early winter these were the young rutted bulls, thereafter the one-year-old calves and, in late winter, the pregnant females. In 1852 the border between Norway and Finland was closed and the human-reindeer migration routes from the coast to the forest areas were shut down (Itkonen). Closing the border was a lengthy process. The official reasons given for doing so were that high numbers of reindeer migrated from Norway to Finland, damaging crops and lichen pastures, and that forest reindeer owned by Inari Sami herders were joining the herds going back to Norway (Itkonen; Enbuske; Jouste). As a result, many families moved from Norway to Sweden with their herds to continue the winter migration to Finland, as the border between Sweden and Finland was still open. The niche based on pasture rotation was re-arranged among the Sami families, who had used lands in Norway and Finnish Russia. However, grazing pressure increased in some areas in northern Sweden, which led to a deterioration of relations between Sweden and Norway. Eventually, in 1883, a law regulating human-reindeer movement between the countries was passed, and by 1889 the border between Sweden and Finland was also closed (Itkonen; Nakkalajarvi: 42-54; Jouste; Koch and Miggelbrink). In spite of the closure of the border, the nomadic Sami of Utsjoki herded their reindeer to Norway until the 1860s (Itkonen). An old herder recalls the old pasture rotations: During those years when there were no fences separating co-operatives, reindeer foraged in their natural ways - there were rutting places, calving places and winter areas. And once the sun began to rise, the reindeer rose up on the mountains; people moved with the reindeer, followed them and remained with the herd. In summer time reindeer grazed in the coastal area of Varangerbotten (in Norway) and later (winter) went all the way to the Saariselka forest area (in Finnish Russia). The main thing was not to mix up different herds" (M1). Over time pasture rotation diminished and herders ended up with smaller pasture regions in Utsjoki, in Finnish Russia (Itkonen). This meant that reindeer were herded nearly 12 months per year on the same pasture lands. The carrying capacity of the land was exceeded (Jouste:47). Between 1878 and 1882 there was a dramatic decrease in the reindeer population, from 31,683 to 19,633 animals (Jouste:43). In 1898, reindeer herding in Finnish Russia was organized in a system of geographically defined co-operatives and the old nomadic routes were discontinued by the end of the century (Kortesalmi). The border closures caused drastic changes within the herding communities. The decrease in pasture land reduced the availability of winter forage. The Russian Czar's act mandating sustainable use of reindeer pastures brought out the characteristics of reindeer in a new light; grazing and trampling negatively affected niche construction and reindeer became key constructors of the niche for the time being. Neither animals nor herders had possibilities for adaptation, but rather were forced to seek new land in the more southern, forested areas of Finnish Russia; they sought to enlarge their niche, because there was still room for new people and herds farther south (Jouste). Although there have been massive moth outbreaks throughout the past centuries, hardly any old documents on the outbreaks exist from Finnish Russia. There were shifts in the elevation of the birch tree line already during the 19th and early 20th century in Abisko, Sweden. There are clear indications that the combination of mass moth outbreaks and reindeer browsing has destroyed mountain birch forests since the beginning of the Holocene (Holtmeier and Broll). In the years 1902-1903, moth outbreaks caused severe damage to the fell vegetation. Documents from the 1920s indicate that Sami herders gradually abandoned campsites in the affected areas (Emanuelson; Cairns and Moen; Van Bogaert et al.:918-917).

autumnal moth, betula pubescens ssp czerepanovii, climate change, global warming, indigenous knowledge (ik), mountain birch destruction, niche construction theory (nct), professional knowledge, reindeer herding, winter moth

PMC4374085_02

Female

In northern Utsjoki, mass outbreaks of autumnal moths have been documented for 1844, 1905, 1909, 1927, 1957, 1965 and 1966 (Holtmeier et al.). One herder recollected the following from the 1950s: "I remember this time, I was less than 20 years old... My late father told me that the area was eaten some 35 years ago, and there were only stumps of this height left; nothing had grown afterwards. This was around 1920-1930, and no new trees have grown back in this area" (M2). This story most likely refers to the moth outbreak of 1927. The interviews allow us to evaluate construction of the niche, with its temporal and spatial dimensions. The main driver of the spring migration of reindeer is the need to have a peaceful, dry and mosquito-free calving site with good access to fresh green forage. If a destroyed birch forest was located at a calving site or was on the reindeer's route to the summer pasture, the herds still headed to these sites, led by mature females (Turi). The insect harassment made the reindeer head uphill on the fells to where there were fewer mosquitoes, and the herders then had an easier time managing the animals, which were said to be "softened by mosquitos" . The significance of permanent summer pasture areas comes out clearly in the herders' accounts: "There were no fences on the fell, just smokes, and reindeer came to sleep by the smokes during the day, when the mosquitoes were worst. In daytime people just walked around among reindeer and calves and cut earmarks. At night time the reindeer left; it was not hot, there were not that many mosquitoes and they went to eat all together" (M3). A few years after a mass moth outbreak, wavy hair-grass (Deschampsia flexuosa) colonized the soil around the birches due to the combined impact of nutrients from moth larva faeces, increased light reaching the ground after the death of the birch canopy and decreased competition given that the larvae also destroy the dominant dwarf shrubs (Rybraten and Hovelsrud). As a herder from Kaldoaivi explained: "It went like this; first there was lichen, then autumnal moths ate the buds, then there was grass, this height; the grass killed the lichen. Our reindeer were really fat; then the grass ran out and mosses came, which meant no more nutrition (M6). As new forage appeared, the reindeer had no need to make any immediate changes. After 4 to 10 years, however, the disappearance of the grass affected the movements of the female reindeer and each year they had to enlarge their foraging areas. Changing the pasture rotation is a slow process, as seen in Abisko, Sweden, where the damaged pastures were abandoned slowly (Van Bogaert et al.). Both the moth outbreaks and border closures were more serious and permanent incidents than the occasional harsh winter weather. Negotiations were conducted and new arrangements made between the siidas, which were forced to change their nomadic routes. In the worst case, the herders started to lose their reindeer for good. Reindeer took on the role from the moths as key constructor of the shared niche and modified their own forage resources by depleting them. Moths first destroyed the primary grazing lands of reindeer, after which the reindeer, as flexible herbivores, carried on the destruction by browsing the damaged birch trees and later grazing on the new grass that appeared. Because parts of the niche were abandoned, the reindeer were forced to extend their pasture rotation to new lands. Here one can see a niche being constructed in a positive way by the action of an animal itself. Until the 1950s reindeer were herded intensively in northern Finland (Kortesalmi). During disastrous years reindeer tended to expand their niche onto new pastures, as they had before. Tensions emerged between the members of different co-operatives. From the perspective of forest herders in the southern parts of the herding area, the big northern herds were a threat in forest areas, as the herders were afraid of losing their reindeer on the fells during late spring. Between 1960 and 1990 the present system of fences between co-operatives was introduced. The niches became "permanently" constructed, which mostly benefitted the small reindeer owners in forest areas. During hard years fences prevented reindeer looking for new forage or acting in enlarged niches. At the same time, extensive herding had replaced intensive herding because of "the 1960s snowmobile revolution" (Pelto et al.; Helander-Renvall; Nakkalajarvi). This meant that reindeer moved inside the fenced co-operatives without people herding them (Helle and Jaakkola; Vuojala-Magga et al.; Turunen and Vuojala-Magga). During this era of fenced and permanent herding co-operatives, diminished land use, severe winters and moth attacks, the negative ecological inheritance that emerged as a selection pressure favoured the fittest reindeers. Moth outbreaks in the 1960s destroyed about two-thirds of the mountain birch forests in northernmost Finland (Tenow). For example, in the year 1964-65 in Utsjoki, autumnal moths defoliated 1350 km2. One of the herders described the situation as follows: "They just ate everything, the ground vegetation, too. It's just open, from here all the way to the north, to Pestausselka 10 km...[] There is nothing but open, flat (landscape) once you drive some 20 km to Inari. There used to be birches before. These green caterpillars, 2 or 3 on each leaf - just count how many there were in each tree. It was just ... you should just listen to it." (M6). According to herders, "the oddest thing was the green leaves in the autumns; after the moth outbreak if the weather is warm enough, green leaves will sprout." (M7, F1). These late-summer leaves attracted reindeer to browse again. Wavy hair-grass, which reindeer grazed on (Rybraten and Hovelsrud:323), grew well for many years before it disappeared and the landscape changed into open land with black soil, like "the surface of the moon". (M1). As one of the herders noted: "The foliage destroyed by autumnal moth outbreaks in the 1960s has not yet recovered; what we see is a biological death; it has been a poison (M8). What had been forests became open tundra (Lehtonen and Yli-Rekola; Haukioja et al.; Klemola et al.:354). Still today rotten birch stumps or peaty hummocks signal former birch habitats (Holtmeier et al.). The birch defoliation in 1960 was most probably connected to the combined response to mass moth outbreaks, reindeer browsing, rotting roots and cold summers (Lehtonen and Heikkinen; Holtmeier et al.; Holtmeier and Broll; Holtmeier:7; Huttunen et al.). There has been discussion regarding the role of reindeer in determining the location of the birch tree line. Whether reindeer grazing should be considered a disturbance for fell areas is a complex issue (Kallio and Lehtonen; Helle and Kojola; Lehtonen and Heikkinen; Oksanen et al.; Helle et al.; Helle, den Herder and Niemela; Holtmeier et al.; Holtmeier and Broll; Riipi et al.; Holtmeier). What is more, there is not much scientific evidence for the recovery of forests after the moth outbreaks in the 1960s, because high reindeer numbers caused considerable grazing pressure on birch forests. In Kaldoaivi and Paistunturi, reindeer numbers rose rapidly from their minimum in 1974, reaching their maximum in the period 1987-1988 (RHA) (Figure 2). Since the beginning of the 1990s, herding in Kaldoaivi and Paistunturi has faced new changes. Summer round-ups, in which calves were earmarked, have been discontinued and this has protected lands and increased the well-being of calves. The composition of herds has changed as well. The number of adult males has decreased, because meat sales are based on the slaughter of male calves; this protects the winter pasture lands (Heikkinen). Finally, in the 1990s herders changed the free-ranging system to one of spring herding with hay. Owing to this, the herds are more resistant to harsh winters and the rest of the delicate lichen cover can be protected (Vuojala-Magga et al.). Since the 1960s, humans have become indirect key constructors by establishing permanent niches - fenced-in co-operatives - on a smaller scale than ever before. People had no experience-based knowledge of seasonal pasture rotation inside the fences. This system relied on the reindeer to find forage in any conditions. Access to a temporally extended niche was not possible. Moths and reindeer became key constructors one after another during the years of mass moth outbreaks. As there was no old solution for overcoming the hard times, herders had to apply the traditional systems of herding and knowledge of the herd's behaviour/social system in new ways with new technology. This can be seen as an adaptive process in response to new ecological inheritance in a specific, restricted environment. The herders gradually took on the role of niche constructors in tandem with their animals. The co-operation between herders and reindeer can be seen as increased domestication of reindeer (Helle and Jaakkola; Vuojala-Magga et al.; Turunen and Vuojala-Magga). According to the IPCC, the increase in the global mean surface temperature for the period 2081-2100 relative to 1986-2005 is projected to be in the range of 0.3 to 4.8 C. The Arctic region will warm more rapidly than the global mean. Due to warming, both coniferous and mountain birch forests are expanding northwards and upwards on the fell slopes. Fast-growing graminoids, herbs and shrubs may replace slowly growing lichens (Kullman and Oberg; Turunen et al.; CAFF). Similar observations have been made by herders: "There has been enormous growth of birches. The trees and leaves are so dense on the riversides that you can no longer see the rivers (M1, M8). Those areas (destroyed) in 1964 have been regenerated and are now dense with birch trees (M1). It is predicted that the combined occurrence of mass outbreaks of autumnal moths and a new invasive species of winter moth will be more frequent, because milder winters will increase the survival rate of moth eggs (Neuvonen et al.; Ayres and Lombardero; Logan et al.; den Herder et al.; Klemola; Ammunet, Ammunet et al.). For example, at Kevo, in northernmost Finland, the number of days with a minimum temperature below -36 C (critical for egg survival) decreased during the period 1962-2013 (FMI) (Figure 3). The winter moth has already now expanded its range to continental areas of northern Finland (Jepsen et al.; Klemola; Karlsen et al.). In the years 2006-2008 (2009) the destruction of birch forest in the Nuorgam and Polmak areas of Utsjoki was caused by winter moths. It was a new experience for herders: "I went to catch whitefish with my cousin. I was driving in front of him, and I stopped, and asked, 'Can you see ... that the ground and soil are alive?' There were these balls the size of a human fist - worms stuck together - awful balls full of life; they were greenish worms and just full of life. They had just eaten all the birches, and it was (as late as) September (M2). Studies on the effects of warming and reindeer browsing on mountain birch growth have produced conflicting results (Kallio and Lehtonen; Lehtonen and Heikkinen; Oksanen et al.; Helle et al.; Suominen and Olofsson; Helle, den Herder and Niemela;Cairns and Moen). Helle claims that where regeneration of mountain birch is inhibited by herbivory, the forest will gradually change into tundra. Where there is intensive browsing by reindeer, birches exhibit a typical apple tree-like shape, with no lower branches (e.g. Kallio and Lehtonen; Oksanen et al.; Helle et al.; Suominen and Olofsson:240; Holtmeier and Broll). A hypothesis regarding the removal of the "lichen barrier effect" maintains that heavy reindeer grazing could lead to the decline of the lichen cover, which would then make upward migration of the tree line possible (Helle and Aspi; Tommervik et al.). This occurs because lichens can inhibit seed germination and growth of seedlings and sprouts through chemical and physical impacts (Brown and Mikola). On the other hand, reindeer herbivory could act as a buffer countering the rise of the tree line due to warming (Helle and Aspi; Virtanen et al.; Tommervik et al.; Bond; den Herder et al.; Kaarlejarvi). A recent study indicates that large mammalian grazers may slow down vegetation changes and that moderate grazing pressure could protect small tundra forbs from being outcompeted by taller plants under climatic warming (Kaarlejarvi). The connection between reindeer grazing and moth outbreaks is a delicate issue for herders. The ways in which this topic is addressed depend on the nature of the livelihood. Herders who earn a substantial proportion of their income from other sources, for example tourism, might attribute the signs of erosion in fell areas to high numbers of reindeer: "We only need to have a couple of severe years...before desertification starts" (M9). When discussing future birch destruction, herders recalled their past experiences. They know that reindeer are able to use 200 to 300 plant species for nutrition (Warenberg et al.) and that, in addition to their mountain birch forests, the regions of Kaldoaivi and Paistunturi herding co-operatives have vast wetlands: "There will be always green somewhere, like willows, and birch trees among willow areas are always undamaged; there is grass in those areas. Once damage occurs, the reindeer seek new green areas where they can eat a lot of different types of green plants - like blueberry and whatever" (M1). "If there is pressure on the soil, the number of reindeer will decline and then small reindeer owners will be out first" (F2). This means that with higher reindeer numbers there is a greater possibility to sustain the livelihood. "We might well face a hard situation and, indeed, we are getting ready for this - nature has taught us.... We have been prepared for this type of situation; we will use various means to overcome and cope and get through the hardships. Those who do not bother to work will drop out (of reindeer herding) (M1).

autumnal moth, betula pubescens ssp czerepanovii, climate change, global warming, indigenous knowledge (ik), mountain birch destruction, niche construction theory (nct), professional knowledge, reindeer herding, winter moth

PMC9082665_01

Male

A 69-year-old man reported recurrent fever and arthralgias without other accompanied symptom for 1 year. His C-reactive protein (CRP), procalcitonin (PCT), erythrocyte sedimentation rate (ESR), and serum ferritin (SF) levels were strikingly high, but evaluations for infectious (such as tuberculosis) or rheumatic conditions (such as giant cell arteritis) were unrevealing (Table 1). Peripheral blood analyses demonstrated macrocytic anemia (Hb 92 g/L and MCV 112.8 g/L) and mild thrombocytopenia (Plt 76*109/L). Bone marrow (BM) examination showed no myelodysplasia but presence of +8. Additionally, a next-generation sequencing panel for autoinflammatory diseases was performed and found a heterozygous NLRP3 R675Q missense mutation. Family history was unremarkable. This mutation of NLRP3 was not reported to be pathogenic previously and identified as uncertain significance. Bioinformatics protein function prediction indicated this mutation was benign. A working diagnosis of autoinflammatory syndrome with trisomy 8 was established and the patient has a prompt response to dexamethasone 10 mg per day. Methotrexate 10 mg per week was subsequently added to facilitate glucocorticoids (GCs) tapering. However, fever and CRP resurged during reduction of GCs. Methotrexate was stopped and a therapeutic trial of tofacitinib 5 mg twice daily was initiated at the treatment of 25 mg prednisone per day, after discussion and agreement achieved with the patient. During the following 16-month follow up, tofacitinib was titrated to 15 mg/day and prednisone reduced to 15 mg per day as maintenance. Attempts to reduce either tofacitinib or prednisone to a lower dosage incurred flare of symptom or inflammatory markers. The patient remained stable and underwent regular follow up to date (Figure 1A).

janus kinase inhibitor, auto-inflammation, clonal hematopoiesis, myelodysplasia, trisomy 8

PMC8383638_01

Female

A 22-year-old woman, Gravida 2 Para 1 Living 1 with 35 weeks of gestation with previous one lower segment cesarean section (LSCS) was referred to our department as a case of 35 weeks pregnancy with GPA with nephritic syndrome in remission. Her past history revealed the disease course, which started 1 year back with painless skin lesions (vesicles and papules) over upper and lower limbs, with recurrent bilateral flank pain and occasional episodes of syncopal attack. Further she developed hemoptysis and breathlessness requiring critical care admission at private hospital in Lucknow, India. On evaluation then, revealed presence of hypertension, perinuclear ANCA (P-ANCA) positive, hemoglobin (5.4 g/dL) suggesting severe anemia, her renal function test (RFT) was impaired, chest X-ray showed bilateral pneumonic consolidation, based on above findings, a diagnosis of ANCA-associated vasculitis (AAV) with pneumonia with severe anemia with acute kidney injury was made. The skin lesion was biopsied too, the histopathology however, had no features of vasculitis. The induction therapy commenced with intravenous pulse administration of CYC and methylprednisolone. In addition, she was also started on antihypertensive therapy with tablet amlodipine and losartan and received four units of packed cell transfusion. She responded well to the treatment and was discharged on tapering doses of oral prednisolone and maintenance therapy with oral azathioprine (AZA) and antihypertensives to continue. Besides this she also gave history of 6 months of antitubercular (ATT) therapy in view of pulmonary tuberculosis few months before conception. She conceived during remission phase and was continued on AZA and amlodipine. At around 30 - 32 weeks, patient herself stopped AZA and Amlodipine. Later at 35 weeks, she was referred to All India Institute of Medical Sciences (AIIMS) nephrology department in view of nephritic syndrome, and AZA was restarted, and she was further referred to our department. She was admitted in view of high-risk pregnancy. All her previous antenatal investigations in the current pregnancy were found to be normal including the anomaly scan. On admission, detailed clinical and laboratory evaluation was done. Her blood pressure was found to be normal. The laboratory evaluation revealed ANCA was negative, RFT values (blood urea nitrogen (BUN) 34 mg/dL, serum creatinine 2.57 mg/dL, urea 52 mg/dL, uric acid 8.3 mg/dL, urine albumin to creatinine ratio (ACR) 1,525.76, urine creatinine 21.19 mg/dL and urine microalbumin 323.52 mg/L. Fundoscopy revealed normal finding, ultrasound was suggestive of fetal growth restriction (FGR) and abnormal umbilical Doppler changes. The pregnancy was terminated at 37 weeks owing to worsening renal function (on serial RFT) with previous LSCS with FGR with delivery of an alive healthy female baby of birth weight 2.05 kg with Appearance, Pulse, Grimace, Activity, and Respiration (APGAR) score of 10 in 1 min and 5 min. She remained in remission in her post-partum period and was discharged on maintenance therapy with oral AZA in consultation with nephrologist. At Present, both the mother and the baby are doing well.

antineutrophil cytoplasmic antibodies, granulomatosis with polyangiitis, granulomatous vasculitis, microscopic polyangiitis, wegener’s granulomatosis

PMC4404509_01

Male

A 44-year-old man with a history of benign gastroesophageal reflux disease (GERD), with irregular use of IPP, visited the emergency department with the chief complaint of intermittent fever for 3 months. Body weight loss (11 kg/month), abdominal fullness, poor appetite, and general malaise were also observed. He had no significant history of tuberculosis, and no relevant familial history. On direct questioning he admitted to have night sweats and abdominal pain. The patient said that he had received outpatient treatment followed by oral antibiotics. Unfortunately, his condition worsened with intermittent chills and body weight loss, so he was referred to our hospital. On admission, we found a mildly cachetic man. No jaundice was noted by examination of the palpebral or bulbar conjunctiva, but he was found to be pyrexial (38.7 C on admission). His heart rate was 91 beats/min, blood pressure was 135/89 mmHg, respiratory rate was 18 breaths/min, and oxygen saturation was 100% under normal conditions. Physical examination revealed mild right hypochondrial knocking pain with right hepatomegaly. Palpation did not reveal any abnormalities in the gallbladder or spleen, no abnormality was noted by chest percussion and there was no lymphadenopathy. The results of laboratory studies showed the following: an elevated C reactive protein (CRP) level of 152 (normal less than 10 mg/L). a mildly elevated erythrocyte sedimentation rate (ESR), and hyponatremia at 121mEq/L (Normal serum sodium levels are between approximately 135 and 145 mEq/L); a normal potassium value at 4.16 mEq/L (normal range between 3.5 and 5.0 mEq/L); white blood cell count (WBC) of 8500/mL (normal range, 3500-9100/mL); hemoglobin, 10.9 g/dL (normal range, 13.5-18 g/dL), platelet count, 280,000/muL (normal range, 157,000-377,000/ muL); aspartate aminotransferase (AST), 18 IU/L (normal range, 11-39 IU/L); alanine aminotransferase (ALT), 25 IU/L (normal range, 4-38 IU/L); total bilirubin, 2.2 mg/dL (normal range, 0.2-1.0 mg/dL); elevated creatinine, 3.2 mg/dL (normal range, 0.6-1.5 mg/dL); blood urea nitrogen (BUN), 21 mg/dL (normal range, 9-23 mg/dL). Prothrombin time was within normal limits. Further evaluations, including tests for human immunodeficiency virus, carcinoembryonic antigen, cancer antigen 19-9, alpha-fetoprotein, prostate-specific antigen, serologic diagnosis of hydatid disease and amoebic hemagglutination were all negative. Several sets of blood and sputum cultures were negative for bacteria, fungus, and acid-fast bacilli. Abdominal ultrasound revealed marked hepatomegaly with a tumor with an unclear border in the VIII subsegment of the liver consisting partially of hypoechoic mass, with the hyperechoic area measuring 7 cm. No ascites or adenopathy was seen. Similarly, Abdominal computed tomography (CT) revealed a low-density lesion approximately 7 cm in diameter at the SVIII segment, showing various fat concentrations. Chest X-ray examination was normal (Figure 1, Figure 2). Therefore, we scheduled a liver biopsy in order to rule out malignancy and to have a definitive diagnosis. The direct appreciation of the exudates did not reveal bacteria and histological study suggested an inflammatory pseudotumor with Langerhans giant cells and without caseous necrosis. Anti-TB medications including isoniazid, rifampin, ethambutol, and pyrazinamide were administered accordingly. The fever subsided within 1 week, and the patient's appetite was restored gradually. The patient completed the 6-month course of medication (2 months with isoniazid, rifampin, ethambutol, and pyrazinamide, followed by 4 months with isoniazid, rifampin, and ethambutol) without severe adverse events. WBC count, CRP, and ESR all returned to normal levels. The patient's appetite and body weight were restored to previous levels. The follow-up abdominal CT scan revealed that the lesion at the S8 segment had decreased in size after 4 months of treatment and disappeared after one year of follow up. Follow-up was continued for six years, and the patient is still healthy.

tuberculosis, antitubercular therapy, liver, tuberculome

PMC3992755_01

Male

A previously healthy 23-year-old man presented with fever, occasional headache and vomiting since 4 days, one episode of generalized tonic clonic seizures 2 days prior to admission to the hospital followed by altered sensorium and left sided weakness. At admission to the neurological services, he was afebrile, not opening eyes to painful stimuli. Neurological examination revealed Glasgow Coma Scale (GCS) of 7/15, E1V2M4 with left hemiparesis. Both pupils were asymmetric and not reactive to light. The extraocular movements were restricted and ocular fundus revealed blurring of disc margins. Deep tendon reflexes were brisk and plantar response was extensor on the left and flexor on the right side. Routine hematological and biochemical parameters were normal. The serological tests for HIV, HBsAg, homocysteine, rheumatoid factor and antinuclear antibody were negative. Antemortem cerebrospinal fluid (CSF) analysis could not be done as lumbar puncture was clinically contraindicated. Electrocardiogram showed T wave depression in V1-V4 leads. Chest X-ray revealed inhomogeneous opacities in the left mid and lower zones with bilateral hilar prominence. Cranial computed tomography (CT) scan highlighted hemorrhagic lesion in the right thalamus and right medial temporal lobe with multiple cerebral and cerebellar ring enhancing lesions. MRI brain [Figure 1a-e] revealed heterogeneous mixed signal intensity changes in the right thalamus, caudate, medial temporal region suggestive of hemorrhagic infarct with extensive perilesional edema extending into right internal and external capsules and corona radiata. The lesions bloomed on flash 2D sequences suggesting accumulation of paramagnetic substance, due to evolving hemorrhage. Lesions which were iso to hyper intense on T1WI and predominantly hypo intense on T2WI (T2 shortening) were noted in the right cerebral peduncle of midbrain suggestive of tuberculoma. Diffusion weighted imaging (DWI) revealed hyper intensity in the right thalamus, medial temporal and midbrain (facilitated diffusion) and hypo intensity in pons (restricted diffusion). Hemorrhage was extending into the lateral ventricle in both the occipital horns. The third and lateral ventricles were dilated with minimal periventricular hyper intensity suggestive of uncompensated hydrocephalus. Multiple rounded lesions iso intense on T1 and hypo intense on T2WI suggesting tuberculous granulomas were noted in the left side of pons, bilateral parasaggital basifrontal zones and left postero medial parietal lobe. There was diffuse sulcal hyper intensity on fluid-attenuated inversion recovery imaging (FLAIR) images suggestive of meningitis. MR venogram revealed non-visualization of the bilateral internal cerebral veins, vein of Rosenthal, vein of Galen and proximal segment of straight sinus and left transverse sinus (images are not available for documentation). A diagnosis of pulmonary tuberculosis with multiple intracranial tuberculomata and thrombosis of cerebral deep venous system was made. Possibility of cerebral toxoplasmosis was also considered in view of multiple ring enhancing lesions. He received both antituberculous and antitoxoplasma chemotherapy with folinic acid for 5 days. He succumbed on the 6th day of admission to the hospital. Smear from the basal exudates of the brain revealed acid fast organisms by Ziehl-Neelsen stain. Serum and CSF samples collected at autopsy were negative for IgG/IgM antibody to Mycobacterium tuberculosis, Toxoplasma gondii and Cysticercosis. Autopsy confined to the examination of the brain only was conducted 18 h postmortem with informed consent of close relatives. The brain weighed 1200 g and was edematous. Dural venous sinuses and superficial anastomotic veins were patent. The leptomeninges were hazy and had occasional tubercles in the parietal area along the course of the veins. The base of the brain had thick hemorrhagic exudate filling the chiasmatic, interpeduncular and pontine cisterns extending to foramen of Lushka, entrapping the cranial nerves and cerebral vessels. The internal carotid and vertebro basilar system were patent with no evidence of atherosclerosis. The crus cerebri on the right was necrotic and hemorrhagic dissecting down from the thalamus to midbrain and the medial temporal lobe on the right was softened. Bilateral cerebellar tonsilar herniation was noted, in spite of mega cisterna magna. On slicing the brain small tuberculomata were found in the left parietal cortex, pons and cerebellum corresponding to lesions on imaging. The right thalamic nucleus, internal capsule, putamen, hippocampus and right half of splenium of the corpus callosum showed hemorrhagic softening, rupturing into the third and lateral ventricle and extending down. The pons and medulla oblongata were enclosed in hemorrhagic inflammatory exudates. At the lower pontine tegmentum and along the foramina of Lushka on both sides, close to choroid plexus tiny tuberculomas were seen in the cerebellum. On the surface the pontine and cerebellar veins were found thrombosed and enclosed in the exudate [Figure 1f-i]. The histological examination of the representative neuroanatomical areas revealed multiple tuberculomas with caseous necrosis, perilesional edema and reactive astrocytosis. Small venous channels draining into the pontomesencephalic veins and the cerebellar veins were found thrombosed and enclosed in tuberculous inflammatory exudates. Similar to arteries, some of the small veins revealed granulomatous phlebitis. The topographic distribution of hemorrhage lesions correspond to the venous drainage area of basal vein of Rosenthal, anterior and posterior mesencephalic veins. The transverse pontine veins, the retrotonsilar veins of the cerebellum and segment of internal cerebral veins and thalamo-striate veins bilaterally but asymmetrically revealed tuberculous thrombophlebitis along with arteritis of the small perforator vessels, thus highlighting the hemorrhagic lesions and masking the small arterial ischemic lesions. Though the tuberculomas indicate chronic pathology, the acute phlebitis suggests an acute exacerbation of an immune complex mediated granulomatous pathology (Theortical possibility of immune reconstitution secondary to ATT needs to be considered).

central nervous system tuberculosis, magnetic resonance imaging, thrombophlebitis, venous infarct

PMC3992755_02

Male

A 30-year-old agricultural laborer presented to the neurology services with a history of three episodes of generalized tonic clonic seizures, irritability, bursts of anger, abusive behavior and inability to recognize close relatives spanning over a period of 1 year and fever with a head ache for 7 days. At 3 days after the onset of fever patient lapsed into altered sensorium along with urinary incontinence. On the day of admission to the hospital, the patient developed right sided weakness. On examination, the patient was febrile, the rest of physical parameters and vitals being normal. Neurological examination revealed GCS of 6/15, E1V2M3 and right hemiparesis. The patient was not opening his eyes to deep painful stimuli and the extra ocular movements were restricted with papilledema. Both pupils were not reactive to light and dilated. The deep tendon reflexes were brisk with an extensor plantar response on the right side and flexor plantar on the left side. Complete hemogram and peripheral smear examination were normal, but for a total leucocyte count of 15,200 and erythrocyte sedimentation rate of 65 mm/1 h (Westergren). The routine biochemical parameters were normal except for mildly elevated liver enzymes. Tests for HIV and HBs were negative. CSF analysis revealed a cell count of 170 cells (80% polymorphs), protein 117 mg% and sugar -11 mg%. Cranial CT scan revealed multiple disc enhancing lesions both in the cerebral grey and white matter and brain stem with edema and hydrocephalus. MRI revealed [Figure 2a-e] multiple subcortical hyperintensities in the bilateral frontal, parietal, temporal white matter and in the pons and midbrain region on T2 and FLAIR images. A few well defined T2 hypointense lesions suggestive of small tuberculomas were also noted in the subcortical location in the bilateral frontal regions. Heterogeneous signal intensity was noted in the left thalamus and caudate nucleus. These lesions were iso to hyper on T1W1 and predominantly hypointense on T2 weighted images with perilesional edema. The lesions bloomed on gradient imaging suggesting a hemorrhagic component. The hyperintense lesions on T2 and FLAIR showed a mixed pattern of restricted and facilitated diffusion. DWI revealed hyper intensity in right frontal subcortical white matter showing restricted diffusion on apparent diffusion coefficient (ADC) maps. MRI brain revealed multiple discoid irregular enhancing lesions in the white matter extending into grey matter. FLAIR images revealed multiple serpegineous hypointense lesions in high parietal section showing thrombosed cortical veins as hypointense curvilinear structures. The patient received antitubercular drugs and steroids. Clinical diagnosis of TBM with multiple tuberculoma was made. Possibility of cerebral toxoplasmosis and cysticercosis were also considered in view of ring enhancing lesions and the endemicity. However he succumbed on 4th day of hospital admission. Autopsy confined to the examination of the brain alone was conducted 13 h after death following informed consent of the close relatives [Figure 3a-e]. Smear from the basal exudate revealed numerous acid fast organisms on Zeihl-Neelson stain. Post mortem serum and CSF were positive for mycobacterial antibody and IgG and IgM type mycobacterial immune complex and negative for cysticercosis and toxoplasmosis. Brain weighed 1200 g and appeared edematous and congested. The superior sagittal sinus along its entire length was thrombosed with extension into the left transverse and sigmoid sinus and involvement of proximal right transverse sinus, straight sinus and the vein of galen were patent. Several superficial cortical veins over the right posterior frontal and parietal lobes were thrombosed, the parenchyma underlying these vessels being softened and hemorrhagic. The leptomeninges were hazy with creamy exudates and small tubercles along the course of the sylvian fissure and basal cisterns, obscuring the underlying structures. Coronal slicing of the brain revealed a large hemorrhagic lesion in the parasagittal right frontoparietal area involving the white matter with edema reflecting venous pathology. Left basal ganglia and thalamus had ischemic infarcts with zones of petechial hemorrhage, representing reperfusion. The brain stem and cerebellum were covered by thick exudates and in ventral mid brain (substantia Nigra) a tiny tuberculoma was found. Histological examination revealed organizing thrombus in the venous sinuses and major superficial veins. Tiny tubercles were observed in the frontal lobe along the walls of the superficial anastomotic veins. In the subarachnoid space the veins were entrapped in the chronic inflammatory exudates. Numerous Acid Fast Organisms were found in the exudates covering the vessels. The ventricular ependyma was normal. There was no granulomatous response or inflammation in the thrombosed dural venous sinuses.

central nervous system tuberculosis, magnetic resonance imaging, thrombophlebitis, venous infarct

PMC6390538_01

Female

A 25- year-old Sri- Lankan female presented with progressively worsening shortness of breath, orthopnoea and dry cough for three days. Her symptoms were not associated with chest pain, fever, oedema or wheezing. At the onset she noted shortness of breath on mild exertion which progressed to shortness of breath even at rest by third day. The patient reported a good urine output throughout. She was asymptomatic prior to the onset of this illness excepting a mild iron deficiency anaemia for which she was on oral iron treatment and dysmenorrhoea attributed to an ovarian cyst. The patient had undergone an appendicectomy eight months prior to the presentation for appendicitis associated with round worm infestation. Examination revealed dyspnoea at rest, elevated jugular venous pulse, tachycardia with a heart rate of 120/min, blood pressure of 100/70 mmHg on both arms. There was an early diastolic murmur over left sternal edge associated with a thrill and bilateral lower lung field crackles. Rest of the examination was normal. Her estimated body surface area was 1.24m2 with a body weight of 40 kg and height of 140 cm. Investigations revealed white cell count of 7.1 x 109/l (4-11 x 109/l), platelet count of 435 x 109/l (150-400 x 109/l),haemoglobin of 10.9 g/dl (11.5-15.5 g/dl) with mean corpuscular volume of 78 fl (80-96 fl). C- reactive protein was 18 mg/l (< 6 mg/l) and Erythrocyte sedimentation rate (ESR) was 114 mm/1st hour (< 20 mm/1st hour). Renal and liver functions, urinalysis, blood sugar and coagulation profile were in normal range. Electrocardiogram revealed sinus tachycardia with no ischaemic changes. Troponin I was negative. Chest radiograph had findings consistent with pulmonary oedema. Repeated blood cultures were negative. Transthoracic echocardiogram demonstrated ejection fraction > 60%, severe aortic regurgitation with dilated aortic root when adjusted for her body surface area(annulus 21 mm, sinus 34 mm). Aortic valve leaflets were morphologically normal. There was no left ventricular hypertrophy, regional wall motion abnormalities or vegetations. Other cardiac valves were normal. All four cardiac chambers were of normal size. Transoesophageal echocardiogram confirmed the absence of vegetations. She was started on supportive management for acute pulmonary oedema and treatment was initiated as for infective endocarditis empirically. Though she was referred to cardiac surgery team urgent surgical interventions were not performed since she improved with medical management. After completion of four weeks empiric antibiotics her echocardiographic changes and ESR remained unchanged. However, heart failure improved with medical management with complete resolution of orthopnoea and dyspnea being limited to moderate exertion. Intravenous antibiotics were omitted in the absence of convincing evidence of endocarditis. Further evaluation was performed in view of persistently high ESR and aortic regurgitation with no definitive cause. Chronic infections such as tuberculosis, vasculitic conditions such as Takayasu arteritis were considered. Further questioning did not reveal constitutional symptoms, contact with tuberculosis, arm claudication, headache or any neurological symptoms. Examination did not reveal any lymphadenopathy, hepatosplenomegaly, cutaneous or joint involvement, fundoscopic abnormalities, pulse deficit or vascular bruits. Rheumatoid factor, serum cryoglobulins, anti nuclear antibodies and complement levels were normal. Peripheral blood smear revealed rouleaux formation with evidence of mild iron deficiency anaemia. Serum protein electrophoresis and serum Lactate dehydrogenase were normal. Human Immunodeficiency Virus antibodies and Serology for syphilis were negative. Mantoux test and induced sputum for acid fast bacilli were negative. Ultrasound abdomen, Contrast enhanced Computed tomography (CT) of the chest, abdomen and pelvis as well as CT aortogram with arch vessels were normal except mild aortic root dilatation. Bone marrow biopsy revealed reactive marrow with no other abnormalities while bone marrow culture for bacteria, fungi, mycobacteria, brucella and leishmania were negative. Colonoscopy and biopsy did not reveal any abnormality. The patient was followed up for one year with detailed clinical assessment and continuation of medical management of heart failure. She did not develop any new symptoms and her exertional dyspnoea remained static. Her ESR remained above 100 mm/1st hour. Clinical examination about one year after initial presentation revealed a reduced pulse volume of left upper limb with a blood pressure difference (right- 100/70 mmHg, left- 70/40 mmHg). There was a left subclavian bruit as well. But, patient did not have any constitutional symptoms or any symptoms of left upper limb ischaemia. Digital subtraction angiography at that point revealed significant stenosis at first part of left subclavian artery and at the origin of left vertebral artery (Fig. 1). Based on the new findings she was diagnosed to have Takayasu arteritis and was started on prednisolone 1 mg/kg body weight daily with plan for follow up at cardiology and rheumatology units. Six weeks after initiation of glucocorticoids patient remained clinically well and ESR decreased to 25 mm/1st hour. Glucocorticoid dose was slowly tapered. Decision on aortic valve replacement was decided to be made few months later after resolution of active inflammation and repeat cardiac assessment. Ravascularisation for arterial stenosis was not offered in the absence of symptoms of upper limb or cerebral ischaemia. Sequence of events from her presentation to the diagnosis is given in a timeline in Table 1.

acute heart failure, aortic regurgitation, infective endocarditis, pulmonary oedema, takayasu arteritis

PMC9884833_02

Female

Her grandfather committed suicide at the age of 34, the father is alcohol-dependent. During her childhood the patient describes her parents as largely neglectful toward her with a lot of domestic quarreling, which took place in her presence. The relationship with her father was weak and distant and her mother was controlling and emotionally labile with occasional angry outbursts toward the patient. Her parents divorced when she was 22 years old. The patient decided not to pursue the relationships with them as an adult. As a teenager she experienced an incident of sexual abuse at the hands of a peer, who also stalked her for some time after the assault. There is a negative history for psychoactive substance use, somatic illnesses, and positive for self-harm in high school (cutting her skin). The patient first sought psychological help at the age of 17 the onset of major depressive disorder (MDD), after a self-harm episode, when the school intervened and informed the parents. She remained in psychotherapy for around 4 years, assessing it as effective. In that time, she was able to finish college, start working in her profession as well as keep up with several hobbies and stay very active most of the time. Since 2018 the patient experienced a slow decline in her mental wellbeing, with no visible cause or significant life events that may have contributed. Since May 2018 the patient continued psychological treatment in the form of counseling and individual psychotherapy, neither yield any significant improvements in the patient's mood and were overall considered ineffective by her. Once the psychotherapy was terminated by the therapist due to worsening of mental health status (suicidal ideation) and inpatient treatment was recommended instead. Before enrolment in the study the patient had been hospitalized two times in stationary wards (one stay after a suicidal attempt in March 2019) and three times in daily wards, diagnosed with MDD with avoidant personality disorder. In the course of her treatment, dominant MDD symptoms were: depressed mood, lack of motivation, decreased complex activity level, anhedonia, and insomnia. Pre-DBS pharmacotherapy consisted of sertraline, mirtazapine (up to 45 mg), venlafaxine (up to 225 mg), bupropion (up to 300 mg), quetiapine (up to 150 mg), escitalopram (up to 20 mg), and vortioxetine (up to 20 mg) administered for pharmacokinetically adequate periods. In longer observations the best self-reported functioning was during bupropion intake, however none of pharmacological agents provided stable remission or significant improvement in terms of MDD symptoms and functioning. During the hospitalization in November 2019-January 2020 (admitted from the toxicology department after her second suicidal attempt) one course of ECT was performed in the Psychiatry Clinic of the Wroclaw University Hospital. Titration method was used with a total number of eight successful treatment sessions. Final parameters were as follows: frequency = 35 Hz, bandwidth = 1 ms, current = 800 mA, and stimulation duration = 4 s. During the treatment the patient reported teeth aches with no other side effects. Bilateral temporal areas were stimulated with manual electrodes. During each stimulation provoked seizure attack lasted at least 25 s assessed both by EEG and muscle contraction sensor placed on pointing finger not blocked by suxamethonium chloride. Since ECT therapy was implemented before enrolment to the DBS study none of precise assessment tools were used apart from a brief clinical global impression scale (CGI) assessment. After the ECT treatment in parallel with the psychopharmacotherapy (bupropion 150 mg, quetiapine 150 mg) and psychological support a remission of MDD symptoms was observed. Pharmacotherapy during the discharge consisted of quetiapine 150 mg, bupropion 300 mg, and propranolol 30 mg. During subsequent months she returned to full-time job and took part in a TV-video documentary about ECT treatment that was recorded in the Clinic. Four months after ECT a gradual relapse of MDD symptoms was observed. In July 2020 escitalopram (20 mg) was added to bupropion and quetiapine with no significant improvement. After being presented with various treatment options, including maintenance ECT, the patient did not want to take electroconvulsive therapy again. The patients' concern was memory impairment after repeated ECT courses. Even if transient, this would strongly interfere with her work skill and responsibility as an accountant. In September 2020 the patient was recruited to the clinical program of TMS treatment in MDD. It was a randomized sham-controlled study comparing a "classical" FDA-approved rTMS protocol for MDD with an authored intermittent theta-burst stimulation (iTBS) protocol. The patient was randomized into the active iTBS protocol, consisting of a total number of 40 sessions (4 daily), 189 s each, 80% of RMT, 50 Hz. Self-reported improvement of sleep duration and its quality was reported, but only a relatively small reduction of MDD symptoms and no change in functioning were observed after the TMS treatment. Due to the sudden exacerbation of depressive symptoms and appearance of intense suicidal ideations at 9th day of the stimulation, it was ceased. Thus, only 32 out of total 40 sessions protocol-wise were performed. The sudden exacerbation od MDD symptoms in the authors' opinion was not due to TMS stimulation. At the end of October 2020 the patient was recruited to the study of DBS treatment in TRD. In this time the patient met all the inclusion criteria and there were no exclusion criteria present (the suicidal ideations subsided), presented in Table 1. Meanwhile pharmacotherapy was modified:bupropion, quetiapine and escitalopram were withdrawn, for a short period of time amitriptyline (150 mg) was introduced and fast withdrawn due to severe side effects (urinary retention). Vortioxetine (10 mg) and mirtazapine (30 mg) were introduced with partial positive response in terms of sleep quality. In December 2020 a DBS system was implanted bilaterally into the medial forebrain bundle (MFB) area, according to the technique described by Coenen et al.. Two four-contact directional leads (1.5 mm length of each contact and 0.5 mm interspacing), connected to a rechargeable stimulator (Gevia, Boston, USA), were implanted. Stimulation parameters were: 130 Hz, 60 mus and a maximal amplitude of 3 mA. Both bipolar and directional monopolar (cathodal and anodal) were used throughout the study. In January 2021 the stimulation was initiated and a sudden exacerbation of MDD symptoms within 2 weeks was observed. After the adjustment of stimulation parameters and increase of vortioxetine dose to 20 mg an almost total cessation of depressive and "internal tension" symptoms was observed. In the middle of March 2021 the patient reached full remission of symptoms (defined as HDRS <= 7/MADRS <= 10 scores). The patient also reported improvement in self-assessment VAS scales (see Figure 2). Unfortunately, the patient got infected with SARS-CoV-2 (mild severity) and was isolated alone at home. Immediately after coming back to work her MDD symptoms intensified rapidly. At the end of March the patient was admitted to toxicology and then psychiatric ward after a suicidal medication overdose with mirtazapine (1,200 mg) and chlorprothixene (300 mg). During her stay in the Psychiatry Clinic vortioxetine 20 mg and active DBS were continued. Significant improvement was observed after lithium carbonate introduction (3 x 250 per day, orally). However, due to past suicidal attempts and possible risk of such acts in the future finally the stabilizer was changed into lamotrigine (150 mg) and the patient was discharged. Depressive symptoms were subsiding further, a relatively stable 4 months remission was observed until the end of July. Following the study protocol an attempt of parameter modification was performed in order to verify if the improvement could be attributed to DBS. The patient and the rating psychiatrists remained blinded, while the neurosurgeons were unblinded to introduced modifications. A sudden relapse of symptoms with subjective worsening of mental state (see Figure 2) and stimulation side effects were reported (hand tremors, tachycardia, vision blurring and diplopia). After rehospitalization and the adjustment of parameters again the fast MDD remission was achieved with good treatment tolerance. In mid-October 2021 an exacerbation of MDD symptoms was observed, which could be explained by the increased impedance of C6 electrode revealed during check-up. Cessation of stimulation in this area was performed with following fast remission over the next 2 weeks. In mid-November a relapse appeared with no determined cause and the patient asked for the change of pharmacotherapy. It was decided that lithium carbonate (500 mg, plasma level 0.59 mmol/l) and bupropion (300 mg) will be reintroduced additionally to vortioxetine (10 mg) whereas lamotrigine will be withdrawn. A significant response was observed. In January 2022 the patient finished 1st year of active DBS stimulation with improvement in the severity of MDD symptoms and functioning. But starting from March 2022, sleep disturbances and insomnia symptoms appeared, with only partial response to pharmacotherapy changes (firstly doxepine 10 mg instead of chlorprothixene, but with no effect; then promazine 25 mg was introduced with quetiapine increase to 100 mg) and starting from April 2022 an exacerbation of MDD symptoms appeared with no significant stressors appearing in the patient's life. Due to the high level of anxiety, temporary reintroduction of clonazepam 1 mg daily was necessary. An improvement was observed, but together with clonazepam dose reduction, another decline was observed. At the beginning of June 2022 DBS parameters were changed for those used during the period from February to July 2021 with one modification:the cathode was set on the internal pulse generator, and anodic stimulation at the level of the electrodes was introduced. Simultaneously, vortioxetine was increased to 20 mg, lithium carbonate decreased to 250 mg and lamotrigine 50 mg was reintroduced. A fast improvement was observed, but lasting only for 1 month, and in the middle of July DBS was changed from anodic current to bipolar, with parameters similar to those used in February-July 2021, with an exception of one contact remaining turned off due to a high impedance level. No abnormalities were observed in physical examinations and laboratory tests performed each time during hospitalization. Summing up, after 20 months of active DBS stimulation, the patient remained lastly in 3-month remission of MDD symptoms and a significant improvement in global functioning compared to baseline (Table 2): : 96.55% reduction of depressive symptoms by MADRS, : 94.4% reduction of depressive symptoms by HDRS-17, : 87.5% reduction of anxiety symptoms (Figure 2), : 90% increase of social and occupational functioning (Figure 3). Shortly before the DBS implantation the patient decided to start CBT in the Psychiatry Clinic and continued until the present moment. It was considered adequate as it allowed the patient to contact the same therapist on an in-and outpatient basis. The patient is cooperative and attends weekly sessions unopposed. During acute and sudden onset of her depressive episode's interventions are supportive, focused around "getting through" the rough patch, leaving little room for long-term goals. During those episodes the patient was largely inactive, spending time in bed and (if possible) at work with no other activity during the afternoons and weekends. She also remained extremely isolated, limiting her social contacts to forced interactions with her family and/or medical personnel, where conversations are mostly limited to yes/no answers. At the peak of those episodes the patient was anxious, restless, often reporting racing thoughts, insomnia and nightmares including realistic dreams sometimes centered around traumatic past events. On average episodes passed after 3-4 weeks, with a slow decline in anxiety and SI up to a state of slightly lowered but stable mood. During remission or at least improvement the patient typically becomes more active and social as well as more engaged in her therapy discussing future goals, current thoughts and past events, although these changes rarely reach levels that could be considered satisfactory or expected in terms of mental health. Apart from it the patient's current psychological functioning is influenced by a high susceptibility to external stressors and very low resilience. Small external obstacles are difficult to combat for her and her self-efficacy and expected ability to cope are minimal. This is also largely influenced by her recent experiences with her illness, which she feels is entirely out of her control, leaving her with the belief of being unable to control or regulate her emotional states and decisions. However, in the course of treatment, the patient's coping abilities were observed to improve, she is to some extent able to manage her illness in a more constructive way, i.e., keep up some physical activity and manage her stress-load during low-mood episodes. At the beginning of July 2022, the patient noted a gradual improvement in her mood, which remained stable until the end of the observation period covered in this case study (first half of October 2022). During this time the patients' symptoms were stable enough to allow her to formulate and fulfill some long-term goals, i.e., move into her own apartment and manage day -to-day tasks living alone, while working part-time as well as plan and discuss her future career options with her employer. The patient is also able to actively pursue and uphold several relationships with family and friends, including the relationship with her mother, which is now significantly improved. At the same time, for the first time since the decline of her mental wellbeing the patient is able to pursue a romantic interest and is currently involved in a relationship with a significant other. An evaluation of possible comorbid post-traumatic stress disorder was performed based on the ICD-10 criteria and could not be confirmed based on the current as well as previous symptoms, including onset and duration. Despite a previously acquired diagnosis of avoidant personality disorder, the current personality diagnosis (e.g., SCID-5) did not confirm this finding, nor yield a specific PD diagnosis. Immature personality traits do however emerge in the structured interview, other clinical instruments as well as observation and the patient's history. The NEO-PI-R personality inventory yielded high to very high scores in agreeableness, the anxiety and depression subscales of the neuroticism dimension as well as the subscales dutiful and deliberate of the conscientiousness dimension. Extremely low scores were found for the extraversion and openness to experience dimensions. In line with other data these results suggest extreme introversion, high negative emotionality, a tendency to deny her emotional responses coupled with low insight as well as restraint in anger responses toward others, conflict avoidance and high personal standards contributing to the observed anxiety and avoidance responses. Neuropsychological evaluation with the use of the Cambridge Neuropsychological Test Automated Battery (CANTAB) was performed at baseline and 6 months of stimulation. The test battery included a brief cognitive safety assessment (i.e., visual memory, new learning, and reaction time), and depression-specific tasks (executive functions:spatial planning and working memory and emotion recognition). Based on the results the cognitive safety of the procedure could be confirmed by no noticeable decline in the cognitive safety assessment. The patient filled in self-assessment questionnaires that contributed feedback including the patient's perspective. In terms of quality of life (measured by the WHOQOL-BREF questionnaire) during 20 months of DBS stimulation we have observed: : 15.8% increase in psychological domain (from 38 to 44 points on 1-100 scale), : 44.7% decrease in social support domain (from 56 to 31 points), : 20.6% decrease in environmental domain (from 63 to 50 points), : no change in physical domain (44 points). Subjective depressive and insomnia symptoms after 20 months of active DBS compared to baseline (Table 2): : 18.2% reduction in Beck Depression Inventory, : 38.6% reduction in Negative Emotion and 100% increase in Positive Emotion (PANAS), : 75% reduction of insomnia symptoms by Insomnia Severity Index (ISI; indicating no insomnia symptoms after 20 months of stimulation), : 42.8% increase in Pittsburgh Sleep Quality Index with relatively poor sleep quality, mostly due to reported sleep fragmentation and increased sleepiness during the day, although insomnia criteria are not met, : 53.8% decrease of anhedonia intensity in Snaith-Hamilton Pleasure Scale, : 93.3% increase of activity in Behavioral Activation for Depression Scale-Short Form (BADS-SF), : 100% reduction in VAS anxiety, : 80.0% improvement in VAS mood, : 33.3% decrease in VAS concentration, : lack of physical discomfort (VAS). See Figure 4 for more details. VAS assessment was performed during each check-up. Transient side effects of DBS were described in Section 2.3.1, all of them were eliminated by the adjustment of stimulation parameters. No side effects resulting from the location of the wires and the stimulator itself were reported. The answer to the question during the patient's last examination, "Would you have made the same decision about DBS?" was:yes, definitely yes. For detailed information on the treatment timeline, please see Figure 5.

deep brain stimulation, transcranial magnetic stimulation, electroconvulsive therapy, neurostimulation, treatment-resistant depression

PMC4867722_01

Male

Pure acute medial subtalar dislocation without any fractures is very rare and hardly reported in the literature, it represents approximately 1% of all dislocations. This injury is defined as simultaneous dislocation of both thetal on avicular and the talocal caneal joints without a major fracture. It is not commonly seen as a sports injury because it requires transfer of a high energy. Optimal management of subtalar dislocations is immediate closed reduction with procedural sedation. We report a very rare case of a closed subtalar dislocation without any related fractures. A 22 year old male was admitted to the emergency department with pain and ankle deformity following an inversion injury during a basketball game. In his physical examination, the left foot was displaced medially and talus was prominent dorso laterally (A). However, there was not any neurovascular compromise. The X-ray examination revealed medial subtalar dislocation without associated fractures (B, C). A computed tomography scan with 3D reconstruction confirmed the isolated dislocation. Under procedural sedation the reduction was successfully performed by an external maneuver (D). The ankle was immobilized in a short leg cast for 8 weeks. At 24 months follow-up, the patient was autonomous and active without instability at the left ankle.

dislocation, isolated, medial, subtalar

PMC9700436_02

Female

A 60-year old female, black race, with a familiar history of diabetes and a silent personal medical history, presented to the center of Hematology in Cuneo with diffuse itching and cutaneous erythroderma on August 2020. At clinical examination, she had no fever, no night sweats, moderate weight loss, bilateral axillary and inguinal lymphadenopathy (about 2 centimeters), no hepato- or splenomegaly. The initial laboratory tests showed remarkable leukocytosis with absolute lymphocytosis (white cells blood count (WBC) 10,300/mm3, neutrophils 21%, lymphocytes 71%), normal hemoglobin and platelets levels and elevated serum lactate dehydrogenase (LDH) level. Abdominal ultrasound (US) scan showed some enlarged liver hilum and mesenteric lymph nodes. The CT scan and a positron emission tomography (PET) scan confirmed the enlarged activated lymph nodes in multiple sites above and below the diaphragm (bilateral cervical, axillary, iliac, inguinal, mesenteric and liver hilum). Flow cytometry on peripheral blood lymphocytes showed an invasion by a CD3+, CD4+, CD7+ T lymphocytes (87% of total lymphocyte count, 6344 cells/microL), with a monotypic expression of variable region Vbeta 12 of T-cell receptor. Multiple site biopsies (cutaneous, right axillary lymph node and bone marrow biopsy biopsy) showed an invasion by CD2+, CD3+, CD5+, CD7+ and CD4+ T lymphocytes. A diagnosis of SS was made and the patient started systemic treatment with steroids. After an initial clinical benefit on itching and cutaneous erythroderma, in December 2020 the patient showed a new worsening of both symptoms, with increasing lymphocytosis and growing adenopathies. On December 23rd 2020, a second line treatment with mogamulizumab at the standard dose of 1 mg/kg on day 1, 8, 15, 22 of cycle 1 and on day 1, 15 for the subsequent courses, was started. At the screening analyses, the patient was found to be anti-HBc Ab positive, with normal transaminase levels, HBsAg and HBV DNA negative. A standard HBV reactivation prophylaxis was started before starting mogamulizumab therapy. Since the second administration of mogamulizumab, a clear clinical benefit on itching and erythroderma was observed, as well as a progressive reduction of peripheral leukocytosis and lymphocytosis (Figure 1). Six cycles of mogamulizumab were performed and well tolerated, without any complication. At the same time, a bone marrow donor was searched: the patient had no siblings, matched unrelated donor (MUD) research was negative, but the patient had an available haploidentical son. The treatment with mogamulizumab was stopped in June 2021, after reaching an almost complete disease remission, and the patient underwent haploidentical allotransplant. In order to reduce the risk of acute Graft Versus Host Disease (aGVHD), a wash out period of 2 months from mogamulizumab infusion and allotransplant was performed. The restaging of disease showed a complete cutaneous response, a complete regression of peripheral blood lymphocytosis with negative peripheral blood flow cytometry and negative bone marrow cytometry and biopsy and a good partial response on lymphadenopathy. The patient underwent allotransplant in a good global partial response, with a Sorror score 1 (for HBV prophylaxis). The transplant was planned on August 2021, but then delayed until September 2021, because of donor positivity for malaria PCR. After antimalarial treatment and the negativization of plasmodium PCR on two consecutive analyses, the peripheral blood stem cells (PBSC) collection was performed. A cytomegalovirus (CMV) reactivation prophylaxis with letermovir from the day of transplant (the patient was CMV positive) and an antifungal prophylaxis with micafungin were administered. A transplant conditioning regimen with thiotepa-cyclophosphamide-fludarabine, followed by total-body irradiation (TBI) 200 rads, was used. On day 0, she received fresh PBSC by haploidentical son donor, containing a total of 9.56 x 106 CD34+ cells/kg. She started GVHD prophylaxis with immunosuppressive therapy with cyclophosphamide (day +3 and +4 from transplant), mycophenolate from day +4 to day +35 and cyclosporine from day +4. The clinical post-transplant course was good, with neutrophil recovery observed on day +15 and platelets recovery on day +21. A standard anti-infective prophylaxis for CMV, HBV, antifungal, antiviral was performed, as well as a weekly monitoring of CMV, EBV, Aspergillosis and malaria plasmodium. The admission period was complicated only by a grade 1 mucositis, without the need of a parenteral feeding support, and by a methicillin-sensitive Staphylococcus aureus bacteremia with fever lasting one day with prompt response to antibiotic treatment. The patient was discharged on day +28. The post-transplant clinical course was uneventful, without any clinical concerns and no GVHD onset. Now she is on day +150 post-transplant, in good health, with a complete disease remission (PFS not reached) and no GVHD signs.

sèzary syndrome, cutaneous t- cell lymphoma, mogamulizumab, mycosis fungoides

PMC9700436_08

Female

A 57-year-old woman was admitted to the UOC Lymphoproliferative Diseases in Rome on January 2018 with a 1-month history of itching, erythrodermia and lymphocytosis. A skin biopsy showed CD3 and CD4 positive cells and CD7 and CD26 negative cells. After the histological examination, an epidermotropic T-cell lymphoma was diagnosed. Laboratory test showed leukocytosis with Sezary cells, and flow cytometry of the peripheral blood a CD4/CD8 ratio >10 and 90% of CD4+ T-cells negative for CD7. CT scan showed supra- and sub-diaphragmatic lymph adenomegalies. These findings led to the diagnosis of SS, stage TNMB IV A1. From February 2018, the patient received a first-line treatment with interferon-alpha-2a 3 MUI twice a week, prednisone 10 mg/die and extracorporeal photopheresis. On September 2018, due to the worsening of the cutaneous disease, she underwent a second-line treatment with gemcitabine 1000 mg/m2 on days 1-8-15 every 28 days associated with extracorporeal photopheresis. In the meantime, we started the research for a matched unrelated donor, since she had not compatible related donor, considering the allogeneic transplantation: an HLA 10/10 possible MUD was found. On March 2020, the patient had a new cutaneous relapse and thus, a third line of treatment with mogamulizumab as bridge-to-transplant was administered. The dose schedule of mogamulizumab was 1 mg/kg once weekly for the first cycle, in a 28-day cycle, and then 1 mg/kg every two weeks, for a total of 11 cycles: at the end of the treatment, a complete response was obtained with a good tolerance. On February 2021, due to an aseptic necrosis of the head of the left femur that required arthroplasty, the patient discontinued the treatment. On September 2021, after 7 months from the discontinuation of mogamulizumab, blood tests, PET/CT and a new skin biopsy confirmed the persistence of the complete response. Therefore, on November 2021, the patient underwent allogeneic hematopoietic stem cells transplantation from matched unrelated donor HLA 10/10. She was admitted in our hospital and she started the conditioning therapy with TBF-RIC (thiotepa-fludarabine-busulfan) and a prophylaxis for GVHD with cyclosporine, methotrexate and thymoglobulin. The transplantation procedure had no complication and no sign of acute GVHD has been reported. The patient discontinued mogamulizumab one year ago, underwent stem cells transplantation and, after 3 months, a complete remission of SS still persists.

sèzary syndrome, cutaneous t- cell lymphoma, mogamulizumab, mycosis fungoides

PMC8464323_01

Female

A 56-year-old woman presented with a 2-week history of shortness of breath, fever, and productive cough. She had a 3-year history of primary MF. Due to massive symptomatic splenomegaly, ruxolitinib was commenced in January 2020. She had never smoked. She worked as a government officer and had no known environmental exposure to pollutants or pets. She had received BCG vaccination in the past. There has no tuberculosis or cryptococcosis reported in household contacts of this patient. During ten months of ruxolitinib therapy, she presented to the outside hospital with a 3-week history of a cough and fever. The initial chest radiograph (Figure 1A) and computed tomography (CT) scan of the chest showed extensive airspace consolidation in the left lower lobe and numerous fine nodular opacities in both lungs. There were enlarged right supraclavicular and subcarinal lymph nodes without pleural effusion. She was diagnosed as having lobar pneumonia and received levofloxacin for seven days without any clinical improvement. Sputum staining for Gram- and acid-fast bacilli (AFB) were negative. The sputum polymerase chain reaction for Mycobacterium tuberculosis (PCR-MTB) was detected. Therefore, pulmonary TB was diagnosed, and isoniazid (H), rifampin (R), pyrazinamide (Z), and ethambutol (E) were initiated. Despite negative sputum culture for TB, antituberculous therapy was continued, and the patient's symptoms subsided. Two months later, she was admitted with a marked deterioration in the shortness of breath, especially on exertion, productive cough, and fever for two weeks. She was treated with oral amoxicillin/clavulanic acid for three days before admission. On evaluation, she was ill-appearing. Vital signs included a temperature of 36.5 C, blood pressure of 110/70 mmHg, heart rate of 92 /minute, and respiratory rate of 20 /minute. Her oxygen saturation was 96% at ambient air. Respiratory examination revealed bilateral crackles and decreased breath sound at the left lower lung. The patient's abdominal examination revealed massive splenomegaly. The complete blood count showed hemoglobin level of 9.3 g/dL, a white blood cell (WBC) count of 52,710 cells/uL (60% neutrophil, 7% lymphocyte, 10% eosinophil, 2% band form, 4% metamyelocyte, 5% myelocyte and 4% promyelocyte), and platelet count of 185,000 cells/uL. Anti-HIV testing was non-reactive. Other blood tests were unremarkable, except for increased serum lactate dehydrogenase (LDH, 1302 U/L) and alkaline phosphatase (181 U/L). Follow-up chest radiography (Figure 1B) and chest CT scan (Figure 1C and D) showed marked progression of bilateral pulmonary abnormalities with newly developed and left pleural effusion and progressive nodal enlargement. Ultrasound-guided thoracentesis yielded 400 mL of slightly turbid, yellow fluid. Pleural fluid analysis revealed WBC of 5266 cell/mm (mononuclear cell of 77%, neutrophil of 23%), protein of 4.62 g/dL (serum protein of 6.07 g/dL), and LDH of 780 U/L. Bronchoscopy performed later revealed minimal whitish secretion was seen along the lower trachea and mild narrowing of the left basal trunk. Bronchoscopy with bronchoalveolar lavage (BAL) and transbronchial biopsy were performed. PCR-MTB and AFB staining of BAL fluid were negative. Gomori methenamine silver (GMS) staining and cytology of BAL fluid showed budding yeasts (Figure 2A). Histopathological sections of the left lower lobe and right upper lobe biopsies showed non-necrotizing granulomatous inflammation (Figure 2B) and organizing pneumonia (Figure 2C), respectively, but showed no organisms on AFB and GMS stains. However, BAL and pleural fluid cultures grew Cryptococcus neoformans, and serum cryptococcal antigen was positive with a titer of 1:1024. The left chest tube was introduced. The lumbar puncture and cerebrospinal fluid analysis were performed and showed no central nervous system involvement. The final diagnosis of combined pulmonary TB and cryptococcosis with extensive pulmonary, pleural and nodal involvement was entertained. She was started on amphotericin B deoxycholate (0.7 mg/kg per day) plus flucytosine (100 mg/kg per day orally) and administration of ruxolitinib was therefore discontinued. Over the following four weeks, the patient had significant clinical and radiographic improvements. Eleven months of oral fluconazole was chronologically prescribed after completing induction therapy for 28 days. She received completing 2 months of intensive phase anti-TB drugs (2HRZE) before cryptococcosis diagnosis then continued anti-tuberculous with 10 months of isoniazid and ethambutol due to possible drug interactions between rifampicin and fluconazole. Upon follow-up, further clinical and radiographic improvements (Figure 3) were observed without any adverse drug reactions.

janus kinase inhibitor, cryptococcosis, pleural effusion, primary myelofibrosis, ruxolitinib, treatment, tuberculosis

PMC7303975_02

Male

A 65-year-old man was admitted to our hospital because of hemoptysis. He presented with chronic empyema caused by Aspergillus spp. in the residual thoracic cavity after treatment for tuberculosis. We performed tube thoracostomy, however it failed because the content of the pyothorax developed a very hard. Because he had low lung function and a decreased performance status, completion pneumonectomy was not indicated. Therefore, we performed surgical debridement and open-window thoracotomy. Intraoperative observation revealed that multiple bronchopleural fistulas were located on the surface of the destroyed right lung, while air leakage and purulent sputum flowed out from the fistulas. Five days after the operation, we attempted endoscopic bronchial occlusion using EWS. He received intubation under local anesthesia and mild sedation with midazolam, and then underwent insertion of a bronchoscope through an endotracheal tube. EWS (7 mm) was placed into the bronchus (right posterior segmental bronchus (B2)) using grasping forceps. Chest CT showed an occluded EWS in the right B2 of the destroyed right lung (Fig. 3A). Although air leakage was not observed just after endoscopic bronchial occlusion using EWS, EWS occluding B2 had fallen into the thoracic cavity because the BPF was larger than 7 mm, and air leakage recurred on postoperative day 8 (Fig. 3B). We again attempted endoscopic bronchial occlusion under local anesthesia and mild sedation. The bronchoscope was deployed into the right upper lobe bronchus through an endotracheal tube (Fig. 4A). After confirming that the air leakage was localized to the right B2, EWS (7 mm) was again placed in the target bronchus (Fig. 4B). Next, ethyl-2-cyanoacrylate (1.0 ml) was injected through the guide sheath into the space between the bronchial wall and EWS (Fig. 4C). Ethyl-2-cyanoacrylate rapidly hardened and changed to a white color about 60 seconds after injection (Fig. 4D). Air leakage was not observed after this procedure and the postoperative course was uneventful, but the patient died of pneumonia in the left lung three months after the procedure.

bronchopleural fistula, cyanoacrylate, endobronchial watanabe spigot, endoscopic treatment

PMC3326964_01

Female

A 22-year-old female was admitted through emergency with sudden onset severe headache, vomiting, and dimness of vision (6/60) in both eyes. She was diagnosed with systemic lupus erythematosus one year ago by clinical and laboratory criteria (ACR) with nephropathy grade three. She had been given pulse cyclophosphamide 1 year earlier (6 doses, 21 days apart each). After that, she was put on oral steroids (prednisolone, 7.5 mg/day oral) and she continued the drug in the intervening period. At the time of admission she was still on oral steroids (7.5 mg/day). She had no other manifestations of lupus and her mental status was normal. She also had no prior visual problems. After admission, the patient developed low grade fever and her dimness of vision progressed. By third day, she had no perception of light in either eye. Local examination of the eyes showed pupils to be dilated and non-reactive. Ophthalmoscopy showed mild papilledema bilaterally. No neck rigidity was elicited. There was bilateral sixth cranial nerve weakness; but no other neurological signs. Ophthalmologists opined that the pathology was not intra-ocular; neurologists were of the opinion that there was a vascular event in cranium. Immediate imaging was advised. Routine laboratory tests showed mild anemia and thrombocytopenia. Her blood glucose was raised (fasting=144 mg/dL), probably due to long intake of steroids. Due to the presence of papilledema, we did a CT scan of brain [Figure 1] which showed a calcified mass in suprasellar region with perilesional edema (black arrow) with obstructive hydrocephalous. There was also mild cerebral atrophy. The Mantoux test of the patient was negative (she was on steroids), sputum did not show any acid-fast bacilli and chest X-Ray was also normal. She had contact with a sputum positive case of tuberculosis 3 months ago. Her hormonal profile was normal. We could not attempt a spinal tap due to hydrocephalous. The Magnetic resonance imaging scan could not be done due to cost factor. In view of the emergent nature of the illness, we started her on oral anti tubercular drugs with an increased dose of oral steroids. Her headache decreased, but vision improved only mildly. Subsequently, after 1 month, a brain biopsy was done and the lesion was found to be calcified granuloma with aggregates of epitheloid cells, calcifications, necrosis, blood vessel destructions, and few scattered caseations [Figure 2]. The lesion did not show any acid fast bacilli, but overall features were suggestive of tuberculosis. A CSF sample collected at time of brain biopsy showed increased cells (45/muL), increased protein (102 mg/dL). AFB stain of CSF was negative; a PCR from CSF was positive for mycobacterium tuberculosis. Repeat CT scan [Figure 3] showed only a mild decrease in the size of the edema; calcified mass size was the same. She was put on anti-tubercular drugs for 1 year. At present her vision is finger counting at three feet.

lupus, suprasellar calcification, tuberculosis

PMC6446050_01

Male

A 66-year-old Caucasian male Physician Assistant was evaluated at the Infectious Disease clinic for ten-pound weight loss and worsening dry cough without fevers, night sweats or hemoptysis. He had a history of controlled type 2 diabetes mellitus, hypertension, dyslipidemia and remote history of latent tuberculosis treated in 1973 with 6 months of isoniazid. He smoked one pack of cigarettes per day during his early adulthood and quit smoking more than 40 years ago. On examination, he appeared weak and anxious with a weight 83 kg that appeared appropriate for his 185-cm height. He had a normal respiratory rate of 16 per minute, pulse of 78 per minute, and a blood pressure of 127/76 mmHg. Chest auscultation revealed good breath sounds with few left upper lobe rhonchi without crackles. The remainder of his exam was normal. Laboratory work-up revealed a white blood cell count of 5600/mm3, with 53.2% neutrophils, 29.2% lymphocytes, 11.9% monocytes, 3.8% eosinophils, hemoglobin 14.3 g/dL and platelet count 219,000/mm. The comprehensive metabolic panel was within normal limits and his HIV 1/2 antibody screen was negative. Chest CT scan showed left upper lung lobe mass measuring 3.1 x 2.6 x 2.2 cm with smaller lower lobe lung nodules and mild left hilar adenopathy (Fig. 1). PET scan followed with findings concerning for malignancy. However, CT guided FNA biopsy was done and showed no evidence of malignant cells with negative routine, fungal and mycobacterial cultures. The patient was referred to cardiothoracic surgery and underwent thoracotomy and partial lobectomy with resection of the lung mass. Pathology exam revealed necrotizing granuloma with acid fast bacilli (Fig. 2). Mycobacterial culture grew Mycobacterium chimaera. Confirmation and susceptibility testing were completed at the National Jewish Medical Center Mycobacteriology Laboratory in Denver, CO with molecular probes using 16S rDNA sequencing and rpoB sequencing. The isolate showed susceptibility/ intermediately susceptibility to clarithromycin, rifabutin and ethambutol with minimum inhibitory concentrations of 4 mcg/ mL, 0.5 mcg/ mL and 8mcg/mL, respectively. It showed resistance to ciprofloxacin, moxifloxacin, linezolid and amikacin with minimum inhibitory concentrations of 16 mcg/mL, 4 mcg/mL, 64 mcg/mL and 16mcg/mL, respectively. The patient was initially treated with a 3-drug regimen including Rifabutin, Clarithromycin and Ethambutol. He had gastrointestinal intolerance to Clarithromycin, and it had to be switched to Azithromycin after 2 months. He also developed an allergic reaction to Rifabutin 6 months into therapy in the form of drug fever and eosinophilia and the drug had to be stopped. He completed the remaining 12 months of antimycobacterial therapy with Azithromycin and Ethambutol with complete resolution of his clinical and radiologic manifestations.

Initial CT scan of the chest showing left lung mass (arrow), nodules and hilar adenopathy (arrowheads).

PMC5012158_01

Female

A 54-year-old female was admitted with 7% TBSA burn to the left arm and hand following a cooking-related flame injury. She underwent daily assessment for 5 days, after which time it was determined that while certain areas of the burn were likely to heal, the majority of the burn required skin graft, and the study was concluded. The perfusion and photographic images are shown in Figure 1. Area 1 was an area determined to require grafting, while area 2 was judged likely to heal by clinical visual assessment. The difference in perfusion of areas 1 and 2 is evident on the first day post-burn, with area 2 having almost double the perfusion of area 1. This magnitude of difference remained steady throughout the study period, despite the absolute values varying over time. Both areas were excised and grafted at operation to provide uniformity and prevent hypertrophic scarring along the wound edges.

burn depth assessment, spy, indocyanine green

PMC5012158_02

Female

A 72-year-old female was admitted with 10% TBSA burn to left thigh, left flank and left upper chest also following a cooking-related accident. She was assessed daily for 5 days and was discharged home after we determined that her wounds will heal with no surgery. The perfusion and photographic images are shown in Figure 2. The difference in area 1 and 2 in this case were smaller than that in the previous case, likely due to a smaller magnitude of difference in burn depth. Unlike Case 1, this patient demonstrated a spike in perfusion on day 4, immediately prior to the assessment of healing and discharge.

burn depth assessment, spy, indocyanine green

PMC5012158_03

Male

A 37-year-old male was admitted with 7% TBSA burn to bilateral upper extremities following a motor vehicle accident. His wounds were evaluated for 7 days and the patient was sent home after it was determined that no surgical treatment was indicated. The perfusion and photographic images are shown in Figure 3. Similar to Case 2, this patient showed a spike in perfusion of both areas on day 3, which then returned to a level similar to previous values on day 4. The absolute difference between areas 1 and 2 was of a smaller magnitude compared to the previous cases, and on day 2 the values were similar enough to be indistinguishable. Neither of the latter two patients required subsequent skin grafting, suggesting that the correct surgical decision had been made based on clinical grounds alone. In all cases the areas determined to be deeper by visual assessment were shown to have reduced perfusion by quantitative assessment; however as indicated above, the magnitude of difference and absolute values both varied substantially between patients and both areas eventually healed.

burn depth assessment, spy, indocyanine green

PMC8165172_02

Female

A 48-year-old woman was diagnosed with AIH (Child-Pugh class A; MELD score, 18) when she presented with the typical histological feature of interface hepatitis on Aug, 2018 (Figure 1). She was being treated for liver injury using methylprednisolone until she first presented with early symptoms of influenza (i.e., fever, cough, and dizziness) on 18 January 2020, and was positively diagnosed with influenza on 19 January 2020 (Table 1). Her chest CT scan showed similar bilateral ground-glass opacities and consolidations as that of patient 1. Moreover, she presented with fatigue, nausea, and anorexia, like patient 1, and further physical examination revealed liver palms, splenomegaly, and the feeling of an irregular liver on touch. Just as in the case of patient 1, patient 2's laboratory results on admission also showed lymphopenia, neutropenia, mononucleosis, and a high CRP level. Although the levels of some of her liver function parameters such as ALT, AST, and alkaline phosphatase (ALP) were in the normal range, the levels of others such as total bilirubin (TB), direct bilirubin, and GGT were elevated (Table 2).

covid-19, sars-cov-2, autoimmune hepatitis, influenza a, liver cirrhosis

PMC8165172_03

Female

A 61-year-old woman was suspected with AIH on September 2019 (Child-Pugh class A; MELD score, 12). On January 25, 2020, she presented with spiked fever that had persisted for seven days and she complained of tightness in her chest (Table 1). Owing to the persistent fever and ineffective antibiotic treatment, a chest CT scan was performed and revealed blurred margins in the left upper lung. A SARS-CoV-2-specific RT-PCR assay was performed, and a positive case of COVID-19 was confirmed on January 30, 2020. Her CT scan showed the hallmarks of a COVID-19 infection, namely bilateral ground-glass opacities. Further, her laboratory results on admission showed leukocytosis and elevated CRP, ALT, AST, GGT, and TB levels. In addition, her blood coagulation function parameters, including D-Dimer, activated partial thromboplastin time, and fibrinogen were elevated (Table 2). Patient 1 was evaluated with a low AIH score (AIH score: 8) with no antinuclear antibody (ANA), smooth muscle antibody, or liver/kidney microsomal type 1 (LKM-1) antibody detected. The baseline liver characteristics refer to her liver function assessment at hospital discharge, 3 months before she was diagnosed with influenza (Table 3). As is shown in Table 3, her MELD score was 7 and R Factor for liver injury was 1.3. After the onset of the H1N1 viral infection, her liver functions remarkably worsen. Initial laboratory tests revealed obviously elevated liver enzymes: AST, 169 U/L; ALT, 201.3 U/L; GGT, 180.3 U/L; and ALP, 115 U/L. Although viral serologies for hepatitis A, B, C, and E were still negative, serum immunoglobulin was 700.2 mg/dL (Figure 2A). Post H1N1 infection, her AIH score rose to 21 with a positive ANA titer of >1:80, and her liver histology revealed features typical of interface hepatitis. In addition, her MELD score and R Factor for liver injury increased to 13 and 5.3, respectively (Table 3). Patient 2 was diagnosed with defined AIH (AIH score: 18). Table 3 indicates her baseline liver characteristics, which refer to her liver function assessment at hospital discharge, 5 months before she was diagnosed with influenza. She was under glucocorticoid therapy until she was infected with the H1N1 virus. Due to this immunosuppressant therapy, although her ALT, AST, ALP, and total protein (TP) levels were in normal range, she had jaundice with elevated TB (29 mumol/L) and GGT (64 U/L) levels (Figure 2B). Her MELD score and R Factor for liver injury increased from 7 to 13 and from 1.3 to 1.6, respectively (Table 3). Patient 3 was diagnosed with probable AIH (AIH score: 12). Table 3 indicates her baseline liver characteristics, which refer to her liver function assessment at hospital discharge, 3 months before she was diagnosed with COVID-19. Her MELD score and R Factor for liver injury were 10 and 1, respectively. From the onset of COVID-19 symptoms, her liver function deteriorated. Initial laboratory tests during COVID-19 hospitalization revealed evidently elevated liver enzymes: AST, 49 U/L; ALT, 142 U/L; GGT, 200 U/L; ALP, 114 U/L; and TP, 62 g/L (Figure 2C). Compared to her liver function before COVID-19, her AIH score elevated to 14 with a positive LKM-1 antibody titer>1:80. In addition, her MELD score and R Factor for liver injury increased to 12 and 3.7, respectively (Table 3). Once she was given systematic glucocorticoids normal liver function was restored. However, liver injury recurred with the highest level of ALT (163 U/L) and AST (85 U/L) after glucocorticoid withdrawal, and more liver protective drugs had to be administered. After infection, all patients received antiviral therapy: patient 1, Oseltamivir orally [75 mg, BID]; patient 2, first Oseltamivir orally [75 mg, BID] followed by pulsed Peramivir [0.6, ivgtt, qd] due to disease deterioration; and patient 3, ritonavir orally [400 mg/100 mg, BID] and interferon alfa-2b [500 wu, BID]. All patients were given systemic glucocorticoids combined with liver protective drugs (glutathione-based therapy) and broad-spectrum antibiotics. In addition, patients 1 and 2 were administered with oxygen inhalation due to their low PaO2 (<60 mmHg). Patient 3 required endotracheal intubation due to ARDS. During hospitalization, the sputum cultures of patient 1 and patient 3 showed the presence of Candida albicans and Stenotrophomonas maltophilia. Normal liver function was restored in all patients post therapy (Figure 2), and the liver assessment score decreased (Table 3). Finally, all patients were discharged from the hospital (patient 1, 1 February 2020; patient 2, 12 February 2020; and patient 3, 10 March 2020) after two consecutive negative results of the RT-PCR assays for H1N1 and SARS-CoV-2 were obtained on nasopharyngeal swabs (Table 1).

covid-19, sars-cov-2, autoimmune hepatitis, influenza a, liver cirrhosis

PMC7750745_01

Female

An 80-year-old Hispanic female with a past medical history of diabetes mellitus, hypertension, and hyperlipidemia was referred to the hematology-oncology clinic for evaluation of anemia, leukocytosis, and eosinophilia. Her original complete blood count (CBC) showed a white blood cell (WBC) count of 15k/microL with 4.8k/microL absolute eosinophil count (AEC), hemoglobin (Hgb) of 11.3 g/dL, hematocrit (Hct) of 35.1%, mean corpuscular volume (MCV) of 95.5 FL, red blood cells (RBCs) of 3.68 million/microL, and platelets of 301k/microL. During her examination in the oncology clinic, she denied weight loss, night sweats, and fevers and had no physical exam signs of hepatosplenomegaly or rashes. A bone marrow biopsy was performed. At the time of bone marrow biopsy, her blood cell counts showed a Hgb of 11.1 g/dL, 222k/microL, a WBC count of 13.6k/microL with a manual differential of 42% eosinophils (AEC of 6.3k/microL; image of peripheral blood eosinophils in Figure 1(a)). Bone marrow biopsy showed a hypercellular marrow for age (60% cellularity) with trilineage hematopoiesis and eosinophilia (19%) (Figure 1(b)). Iron stain on the aspirate smear showed increased ringed sideroblasts (Figure 1(c)). No evidence of reticulin fibrosis was identified by silver stain. Mild dysmegakaryopoeisis was identified. Mild megaloblastoid changes in some erythroid precursors were present. Molecular studies were performed using a targeted myeloid panel by next generation sequencing (NGS) technology analyzing gene mutations including ASXL1, BCOR, BRAF, CALR, CBL, CEBPA, CSF3R, DDX41, DNMT3A, ETNK1, ETV6, EZH2, GATA2, GNAS, GNB1, IDH1, IDH2, JAK2, KIT, KRAS, MPL, NF1, NPM1, NRAS, PDGFRA, PHF6, PPM1D, PTPN11, RAD21, RUNX1, SETBP1, SF3B1, SH2B3, SMC1A, SMC3, SRSF2, STAG2, STAT3, STAT5B, TET2, TP53, U2AF1, WT1, and ZRSR2. Results of sequencing revealed an ASXL1 nonsense mutation, a SRSF2 missense mutation, a TET2 frameshift mutation, and a TP53 missense mutation (see Table 1). Cytogenetic analysis performed showed a normal female karyotype [46,XX]. Fluorescent in situ hybridization (FISH) was performed for PDGFRA/B and FGFR1 rearrangements and were negative. In addition to the sequencing of JAK2 in the NGS panel, polymerase chain reaction (PCR) for JAK2 (V617F) was also performed and was negative for the mutation. At this time, the differential diagnosis included CEL, NOS, and MDS with increased ringed sideroblasts associated with eosinophilia. The patient was closely followed:without medical treatment. The patient presented with diarrhea 9 months after initial work-up. The diarrhea occured approximately two times a week containing loose stools and typically followed a meal. Stool studies for infectious etiologies were performed and were negative. Colonoscopy with random site biopsy showed microscopic colitis with lymphocytic and eosinophilic infiltration and eosinophilic cryptitis (see Figure 1(d)). The diarrhea symptoms resolved after 3 weeks of oral 9 mg budesonide treatment. No additional chemotherapy treatment was given at this time for the patient's eosinophilia. Two years after initial presentation, the patient's WBC count increased as well as the AEC. A second bone marrow biopsy was performed to rule out disease progression and showed markedly hypercellular marrow for age (95%) with marked eosinophilia (Figure 1(e) and (f)). Given the patient's clinical course, colonic tissue infiltration by eosinophils, bone marrow morphologic findings and gene mutations identified by NGS, a diagnosis of chronic eosinophilic leukemia, NOS was made. A cardiac magnetic resonance imaging (MRI) was performed due to a new second-degree heart block to rule out eosinophilic infiltration. The cardiac MRI was negative for eosinophilic infiltration and the heart block was ruled idiopathic as her ventricle sizes were normal with an ejection fraction of 63%. No further work-up was performed for the new onset of heart block. The patient continued to be closely monitored without interferon, hydroxyurea, or any chemotherapy treatment. A third bone marrow biopsy was performed 39 months after initial presentation. The peripheral smear associated with this bone marrow showed 2% circulating blasts with a leukocytosis consisting of eosinophilia (11%, absolute count 4.7k/microL), neutrophilia (absolute count 24.8k/microL), and monocytosis (absolute count 3.9k/microL). Macrocytic anemia (Hgb 9.5 g/dL and MCV 106.4 fL H) and mild thrombocytopenia was also present (143k/microL). Bone marrow aspirate smears show a blast count of 6% with increased eosinophils (15%). There was decreased storage iron present with 40% ringed sideroblasts. Trilineage dyspoeisis was present. Cytogenetics of the most recent bone marrow showed Trisomy 8, 13, and 14, suggesting disease progression (please refer Table 2 for information about disease course). The patient has not taken any chemotherapy agents during her follow-up care for her CEL, NOS to date.

eosinophilia, ringed sideroblasts

PMC5022069_01

Female

A 44 year old lady presented with severe generalized abdominal pain since two days along with multiple episodes of non-projectile, non-bilious vomiting and diarrhea. She had been admitted in another institution for similar complaints twice in the past month. On both occasions, she was managed conservatively for gastroenteritis with bowel rest and antibiotics. She complained of abdominal pain during every menstruation since six months that reduced with oral analgesics. However, the intensity of pain would increase with every cycle and since two months; she also experienced associated diarrhea and tenesmus. She was not on any contraceptive pills. She had undergone a caesarean section ten years ago. She was otherwise stable, her abdomen was soft with diffuse tenderness and bowel sounds were present. Her abdominal radiograph showed small bowel obstruction with faecal loading in the ascending colon. Computed Tomography (CT) revealed a concentric infective/inflammatory thickening of the distal ileum with significant luminal narrowing of the ileocaecal junction and terminal short segment of ileum with proximal ileal dilatation. No complete mechanical obstruction was seen. Mild edematous thickening of the bowel loops with prominent vasa recta, mild surrounding fat stranding and inter bowel fluid (Fig. 1). The findings were suggestive of a subacute partial small bowel obstruction probably due to Crohn's disease. The colonoscopy showed a tight short ileal stricture just inside the ileocaecal junction. Balloon dilatation was attempted. The narrowing recurred as soon as the balloon was withdrawn, hence it failed (Fig. 2). The patient was managed conservatively but she continued to be symptomatic. Three days later, a colonoscopy was repeated and this time dilatation was done upto 15 mm. Submucosal hemorrhages were seen in the colon with ileocaecal ulceration. A differential diagnosis of tuberculosis was also considered. Despite the dilatation, her symptoms did not subside and the patient was taken for a diagnostic laparoscopy. Intraoperatively, a distal ileal stricture with multiple enlarged lymph nodes were seen. A lump was seen at the tip of the appendix, however the base appeared normal (Fig. 3). No other abnormality was found. A laparoscopic right hemicolectomy was done. Postoperatively, the patient recuperated well and was gradually put on diet. The specimen grossly showed a dilated ileal segment, with the stricture being 2.5 cm in length. Pathologically, the ileum showed multiple endometritic foci with fibroblastic proliferation with a secondary stricture. The Appendix also showed multiple endometriotic foci. The immunohistochemistry (IHC) studies showed the glands to be positive for estrogen, progesterone receptors and vimentin. The stroma was positive for CD10 and vimentin. This confirmed the endometrial origin. No mucosal involvement was seen (Fig. 4). However, the caecum and ascending colon were free from endometriosis. Thirty lymph nodes were resected, all of which showed reactive inflammatory changes. The patient was discharged after a week on full diet. She is on regular follow-up with no cyclical complaints and is not on any hormonal therapy.

appendiceal endometriosis, ileal endometriosis, ileal stricture, right hemicolectomy

PMC4314884_01

Female

A 23-year-old female patient presented to the skin department with a large ulcer over the left side of her neck. She also had ulcers over the left axilla and chest wall with a discharging sinus. There was a history of loss of weight, appetite, and on and off fever. She had developed neck swellings two years ago for which she was treated with category II antituberculous therapy (ATT) for 6 months. However, the swellings did not subside, rather she noticed a subsequent increase in their size. She was diagnosed as Rosai-Dorfman syndrome, and was administered systemic steroids for three months. When she presented to us in the skin department, she was ill-looking, malnourished and anemic. She had matted cervical lymphadenopathy on the right side of her neck. There was an irregular ulcer 5 inch x 3 inch, the floor covered with slough over the region of left sternomastoid muscle. The base was indurated and formed by matted lymph nodes. There were two irregular ulcers over the left axilla and chest wall, one of which had a discharging sinus. The ulcers were tethered to the underlying indurated tissue [Figure 1]. Clinically, multidrug-resistant tuberculosis (TB), NTI, and immunodeficiency were considered as differentials. Hemogram revealed anemia and elevated erythrocyte sedimentation rate. There was no leukocytosis. Touch smear and sputum were negative for tuberculous bacilli. Mantoux test was negative. Chest radiograph was normal. She was negative for HIV I and II. Pus culture grew Staphylococcus aureus. Her biochemical parameters were normal. Histology showed lympho histiocytic infiltrate in the dermis. She was empirically re-started on ATT category II along with cotrimoxazole. There was very little clinical response to the above treatment and hence culture was repeated. There was no growth from the discharge on blood agar, MacConkey agar and thioglycollate broth after 48 h of incubation. To establish the cause, culture was repeated, which this time grew non pigmented, smooth colonies on Lowenstein-Jensen medium on 7th day of inoculation at 37 C [Figures 2a and b]. The isolate reduced nitrate was urease positive and sensitive to amikacin and patient was started on injection amikacin. The colonies were confirmed as M. chelonae-abscessus by molecular diagnostic method (DNA sequencing). Since she could not tolerate amikacin, she was started on clarithromycin 500 mg orally. Within 2 weeks of institution of clarithromycin, the axillary ulcer and sinus healed. The ulcer over the neck showed a slow response. At the end of 40 days of clarithromycin, the ulcer over the neck, completely healed [Figure 3]. The patient gained wait, and her appetite improved. Clarithromycin was continued for one more month and withdrawn.

clarithromycin, mycobacterium chelonae, nontuberculous infection, scrofuloderma

PMC6867963_01

Male

A 16-year old boy underwent laparoscopic surgery for varicocele. His past medical history was uneventful, except for febrile seizures during early childhood. He had no allergies, history of recurrent pneumonia or other chronic respiratory diseases. Likewise, his family history was unremarkable. Smoking habits were asked but not disclosed. Complete blood cells count, liver and kidney function tests and first level coagulation studies (platelets count, prothrombin time test, activated partial thromboplastin time, and fibrinogen) were all normal before the general anesthesia. According to the American Society of Anesthesiologists (ASA) risk classification1, he was a healthy patient (ASA 1). Prior to the operation, the patient was given general anesthesia consisting of propofol (2 mg/kg) and rocuronium (0.6 mg/kg), with remifentanil (0.25 mcg/kg/min) for intubation. General anesthesia was maintained with 2% sevoflurane and remifentanil (0.25-0.125 mcg/kg/min). Sugammadex (2 mg/Kg) was administered before extubation (TOF ratio > 0.9). Both surgery and extubation were conducted without any complications and the patient had no obvious signs of upper airway obstruction, neither cough nor laryngospasm. Thirty minutes after waking up, he manifested hemoptysis, dyspnea, and ARF. He was alert, tachypnoeic, and normothermic. His Glasgow Coma Scale was 15, and his initial vital signs were: pulse 80 bpm, blood pressure 90/60 mmHg and oxygen saturation averaging 73% on room air. Arterial blood gas analysis revealed: pH 7.37; pCO2 39.6 mmHg (5.27 kPa); pO2 39.5 mmHg (5.26 kPa); oxyhemoglobin (oxyHb) 73.7%; and HCO3- 23.1 mEq/L. Otorhinolaryngoiatric evaluation with nasal and laryngeal fibro-endoscopy unveiled no evidence of previous bleeding from the upper respiratory tract. Respiratory auscultation revealed diffuse rhonchi, with no other remarkable signs. His initial chest x-ray (Figure 1) showed infiltrative opacification pattern mainly seen in the mid zones with apical sparing suggestive for impaired pulmonary microcirculation, raising the suspect of DAH. To further investigate our hypothesis, a chest CT scan (Figure 2) was performed, which revealed multiple dense opacities with blurred, confluent margins due to diffuse alveolar involvement in the pulmonary lobes. Given the evidence of hypoxemic respiratory failure and the suspect of DAH, the patient was transferred to the Intensive Care Unit, where he was subjected to immediate bronchoalveolar lavage, revealing the presence of abundant blood, but after the bronchoalveolar lavage with 0.9% sodium chloride solution, the bronchial mucosa appeared without signs of pathological lesions. More specifically, three lavage of 50 mLs each were done and afterwards 35, 35, and 50 mLs of BAL fluid were retrieved. Direct microscopic examination showed leucocytes, macrophages and bronchial epithelial cells. Further confirmation arrived from cytologic analysis of his bronchoalveolar lavage secretions which described the presence of blood, 85% of alveolar macrophages and 15% of granulocytes. Hemosiderin was not assessed because hemoptysis started 4 h before and the endoscopic appearance of the bleeding itself appeared to be very recent, undergoing from <48 h. The patient was given fraction inspired oxygen (FiO2) (40%; 12 L/min) by means of a Venturi mask for ARF, intravenous ceftriaxone 2 g per day as antibiotic prophylaxis and intravenous methylprednisolone 1 g per day for anti-inflammatory action for 5 days, while waiting for the results of microbial studies and autoimmune diseases screening. Initial blood tests performed at Day 1 revealed: hemoglobin levels 13.5 g/dl (135 g/L); leukocytosis 14.540 mm-3 (14.54 109/L), of which 83.7% were neutrophils, and normal platelet count (221 x 109 /L). Renal function, liver function, electrolytes, coagulation studies (prothrombin time, activated partial thromboplastin time, and fibrinogen) were all normal. Von Willebrand factor deficiency was also ruled out on the basis of Von Willebrand factor antigen and Ristocetin cofactor activities which resulted within normal range (Von Willebrand factor antigen was 90%, with a normal reference range between 57 and 147%; Ristocetin cofactor was 120% with a normal reference range of 51-147% considering our patient's specific age group). Urinalysis was unremarkable, and direct microscopic exam did not reveal any dysmorphic red blood cells (RBCs). The diagnostic work-up, which included serological exams and blood and sputum cultures for Streptococcus pneumoniae, Haemophilus influenzae, Legionella pneumophila, Aspergillus, Mycobacterium tuberculosis, Nocardia spp., Chlamydia pneumoniae, Mycoplasma pneumoniae, Pneumocystis Jirovecii, Herpesviruses, and the complete respiratory viral panel, ruled out any pulmonary infections. An extensive rheumatological serologic evaluation including CRP, c-ANCA, p-ANCA, ANA, and ENA panel came back negative as well. Lastly, the echocardiography was completely normal, excluding any congenital or acquired cardiomyopathy as well as pulmonary hypertension. Questioned on smoking habits, the boy revealed to be a frequent cannabis smoker since few years. He admitted to have smoked about 1-2 joints per day in the last month before surgery and to have used a marijuana smoking device known as "water bong" at least once. Moreover, he denied having used any other type of street drugs. We therefore performed a toxicological urine test that resulted positive for cannabinoids. Cocaine was not tested since the patient's parents declined their consent. The patient's general conditions rapidly improved after 24 h: he was no longer dyspneic, and oxygen supplementation was stopped on day 2 of hospitalization after a second chest radiograph (Figure 3) revealed the resolution of DAH. He was discharged after 6 days with tapering prednisone. Although he was recommended an ambulatory follow-up, his parents declined.

acute respiratory failure, anesthesia, cannabis, diffuse alveolar hemorrhage, pediatrics, sevoflurane

PMC10242066_01

Female

We here describe a 50-year-old female patient with intestinal BD. The clinical characteristics and treatment measures of the patient are shown in Table 1 . The patient has had recurrent oral and vulvar ulcers since 2003. In March 2004, she developed nocturnal hyperthermia and dark red bloody stools. Colonoscopy showed terminal ileum ulcers and proliferative lesions. Pathological biopsies reported acute and chronic inflammation of the superficial mucosa. Antinuclear antibody (ANA) and pathergy test results were positive, and the pure protein derivative (PPD) test was negative. Indexes such as infection, tumor, and autoantibody series were normal. According to the diagnostic criteria of the International Study Group for Behcet's Disease, and combined with clinical symptoms, laboratory tests, colonoscopy, and pathological findings, the patient was diagnosed with BD. Prednisone (40mg PO daily), cyclophosphamide (50mg PO daily), and mesalazine (4g PO daily) were administered to control symptoms. Prednisone and cyclophosphamide decreased gradually. In December 2005, cyclophosphamide was stopped, and 5mg of prednisone was taken orally daily to maintain symptoms. In August 2007, she developed multiple joint pains. There were no abnormalities in Anti-Streptolysin "O" (ASO), rheumatoid factor (RF), human leukocyte antigen (HLA-B27), and anti-neutrophil cytoplasmic antibody (ANCA). The treatment regimens were adjusted repeatedly according to the patient's clinical symptoms, including prednisone (40mg PO daily), sulfasalazine (3.0mg PO daily), methotrexate (12.5mg PO weekly), thalidomide (100mg PO daily), cyclophosphamide (50mg PO daily) and colchicine (1mg PO daily), etc. In January 2019, the patient's condition worsened with persistent right lower abdominal pain, bloody stools, frequent episodes of oral ulcers, and arthralgia. Colonoscopy showed multiple ulcers in the distal ileum and large protuberant lesions in the cecum and ascending colon ( Figures 1A, B ). The biopsies revealed chronic inflammatory activity of the mucosa with ulcer formation, and no evidence of neoplasia was seen. Considering the patient's recurrent illness, no significant improvement in intestinal mucosal status, and the failure of previous medications, we decided to switch to treatment with anti-TNF-alpha biologics :- infliximab (IFX). We truthfully stated the benefits and risks of using biologics and obtained the informed consent of the patient. IFX was administered with a dose of 300 mg at 0, 2, 6 weeks, and then every eight weeks. The patient reported a significant reduction in oral and vulvar ulcers, abdominal pain, and arthralgia immediately after the first infusion. On August 9, 2019, a colonoscopy showed that the terminal ileal ulcer was better than before. However, there were no significant changes in ileocecal and ascending colon masses. Biopsies revealed acute mucous inflammation, small vessel dilatation and congestion, epithelial hyperplasia on the recessed surface with erosion and inflammatory exudation, and significant glandular hyperplasia and mucus secretion. There was no evidence of granuloma or neoplasia. Intestinal dual-source CT showed obvious thickening at the lower end of ascending colon, soft tissue shadow protruding into the lumen, and abundant blood supply. Endoscopists considered performing endoscopic submucosal dissection (ESD) to be risky. The gastrointestinal surgeon reported that the possibility of colon cancer could not be excluded from the ascending colonic mass and recommended surgical excision to determine its nature. Therefore, after multidisciplinary discussions, the patient underwent a right radical hemicolectomy on September 6, 2019. Post-operative pathology confirmed the mucinous tumor ( Figure 2 ). IFX was suspended. The mFOLFOX6 chemotherapy regimen was administered for four cycles before being discontinued due to the global outbreak of the novel coronavirus. Long-term oral thalidomide (50mg PO daily) to control the disease. In January 2021, the patient's right lower abdominal pain worsened again. Colonoscopy showed multiple large ulcers in the ileum and anastomotic orifice ( Figure 1C ). Enhanced CT of the abdomen showed thickening of the anastomotic wall and the proximal ileal wall of the anastomosis with significant enhancement. The intestinal BD recurred. The immunosuppressive effect of anti-TNF-alpha biologics may be risky for patients with an oncology history. Therefore, combined with the pathogenesis of intestinal BD and previous case reports, we decided to try VDZ for some clinical benefits. On October 9, 2021, the patient received an infusion of 300 mg VDZ (initially at 0, 2, and 6 weeks, then every eight weeks). After a short follow-up of 6 months, the patient reported that her lower abdominal pain and arthralgia were improved. No obvious adverse reactions occurred. The DAIBD score decreased from 85 to 0, and the WBC, ESR, and CRP levels were normal. On September 30, 2022, a colonoscopy showed a completely healed ileal ulcer with a smooth mucosal surface and well-dilated intestine ( Figure 1D ). However, at the 15th monthly follow-up, her oral and vulvar ulcers recurred, and the CRP concentration increased. Therefore, thalidomide was administered to alleviate systemic inflammation. As shown in Figures 3A-C , although all systemic inflammatory indices showed repeat increases, such as WBC, CRP, and ESR, these might be caused by the presence of inflammation outside of the gastrointestinal (GI) tract. As only focused on the GI tract ( Figure 3D ), the DAIBD showed the significant efficacy of VDZ on intestinal BD.

behcet’s disease, case report, intestinal disease, tumor, vedolizumab

PMC4899699_01

Male

A healthy 14-year-old male sustained a fall on his outstretched right hand while playing basketball. On physical exam, tenderness, decreased range of motion, and mild swelling of the right wrist joint was noted. Point tenderness over the anatomical snuffbox was also present. There was a very high clinical suspicion of scaphoid fracture due to the mechanism of injury and physical exam findings. MRI obtained two hours after the injury demonstrated lipohemarthrosis. Fat within the joint fluid was definitely identified using the fat-saturation technique (Fig. 1). Double fluid-fluid levels were seen on both T1 as well as T2 sequences (Figure 1, Figure 2). A fracture of distal scaphoid bone was identified on anatomical (T1-weighted, Fig. 3), fluid-sensitive (fat-saturated T2-weighted, Fig. 4) and volume-rendered images (Fig. 5). The patient was treated with immobilization using a long thumb spica (fiberglass cast) for six weeks. After the removal of cast and physical therapy, the patient fully recovered and returned to normal baseline activity.

ct, computed tomography, mri, magnetic resonance imaging

PMC8847377_04

Female

After the earthquake, all beneficiaries from Counties' retirement homes were temporarily relocated to a hospice in the town of Topusko. In July 2021, 6 months after the earthquake, during the CMHT regular round of home visits, the team was notified about a beneficiary with previously diagnosed schizophrenia that started being hostile toward the hospice workers. The 47-year-old patient articulated that her body is not hers, and her sense of touch is unusual. During the placement in the Topusko hospice, she was treated for pulmonary tuberculosis, asthma, and COVID-19 infection with the introduction of quadruple antituberculosis therapy. She received regular mental health treatment, including 75 mg clozapine and 1.5 mg alprazolam daily. CMHT provided her with psychosocial support in the form of counseling and increased clozapine dose for 12.5 mg daily. One week after the initial visit, CMHT noticed an additional deterioration of her mental state in the form of paranoia toward other beneficiaries. Given the new circumstances, and despite the increased clozapine dosage, the possibility of antitubercular therapy-induced psychosis was considered. Therefore, CMHT transferred her to Dr. Ivan Barbot hospital where eventually the diagnosis of iatrogenic genesis of psychotic exacerbation was confirmed. Upon achieving the remission of psychotic symptoms, she was displaced to the Special Hospital for Pulmonary Diseases and Tuberculosis where she continued treatment for pulmonary tuberculosis.

cmht, community mental health team, crisis, earthquake, severe mental illness

PMC8191076_01

Female

An athletic 14-year-old Asian-American female with no significant past medical history presented 4 weeks after a basketball injury with right knee pain. She was playing in a high school competition when she dove for the ball and fell to the ground. She struck her right knee with the contralateral knee and twisted her right knee as she fell. The right knee was swollen for several days. There was an audible "pop" at the time of the injury. She continued to have pain on the medial and lateral aspects of the right knee which gradually improved. She was able to bear full weight, and she wore a compression knee sleeve. On examination the patient did not have an antalgic gait. The right knee had no bruising and there was no residual effusion. Bilateral knee range of motion was 0 to 145 and painless. There was no tenderness to palpation along the right medial or lateral joint lines and McMurray's test (evaluates for meniscal injury) was normal. The right knee demonstrated normal stability with anterior and posterior drawer tests and with varus and valgus stress (respective tests for anterior, posterior, lateral, and medial ligamentous injuries). The patella was stable without apprehension and painless with the patellar grind test (evaluates for patellar chondral injury). The Dial test was symmetric and normal at 30 and 90 bilaterally without pain (evaluates for posterolateral corner injuries). The neurovascular exam was normal. The patient had no other significant physical exam findings but she was unable to run, jump or twist. Due to her history and her inability to return to sports an MRI was ordered. A six-sequence, closed, 3.0T MRI was completed. A high grade-to-complete rupture of the popliteus tendon was seen at the level of the popliteal hiatus, with retracted tendon distal and medial to the tibiofibular articulation. This tear can be visualized in Figure 1 (axial MRI) as an enlarged cross section of the popliteus resulting from retraction and scarring of the muscle. The posterior compartment of the knee is visualized in Figure 2 (Sagittal MRI), however, the popliteus is not seen in the popliteal hiatus due to the tear (green arrow). It would normally be seen at the posterior horn of the lateral meniscus. There is edema adjacent to the soleus muscle posterior to the popliteal hiatus, deep to the lateral head of the gastrocnemius (blue arrow). This resulted from the popliteus injury. The distal popliteus is visualized (blue arrows) in Figure 3 (Coronal MRI) however a gap is seen where the tendon should attach proximally at the fibular head and lateral femoral condyle (yellow circle). A few proximal tendinous fibers remain. Bone contusions were seen in the posterolateral corner on the tibial plateau and adjacent fibular head. There was no further injury to the posterolateral corner including the lateral collateral ligament (LCL) and biceps femoris. There was no tear of the anterior cruciate ligament (ACL), posterior cruciate ligament (PCL), or menisci. The medial collateral ligament (MCL) and iliotibial (IT) band and were intact. There was no damage to the articular cartilage.

isolated, knee, orthopedic, popliteus, posterolateral corner, rupture

PMC10021091_01

Male

A 14-month-old male patient was admitted to hospital on 19 May 2021 for multiple burns all over his body. The burn area was 25% (superficial second-degree and deep second-degree) of the total body surface area (TBSA). His burns were located on the head, face, neck, chest, abdomen, back, and upper extremities. Deep second-degree burns (5% TBSA) were mainly located on the face, chest, and abdomen. Most of the burns in the remaining areas were superficial second-degree (11% TBSA). The child was healthy in the past and had no history of food and drug allergies. After admission, the patient was treated with fluid rehydration, blood transfusion, antibiotics to prevent infection, tracheal intubation-assisted ventilation, and regular dressing changes on the wound areas (Table 1). From the second to seventh day of hospitalization, the patient had persistent fever; the antibiotics were changed according to drug sensitivity test results to better treat the infection. On the eighth day of hospitalization, tracheal intubation was removed, but the child still had persistent fever, occasional convulsions, eyes staring to the right, and high-pitched cry. Computed tomography (CT, day 8) showed that the intracranial brain parenchyma was scattered with patchy low-density foci, and patchy high-density shadows were seen in both lungs with blurred edges; mild cerebral oedema and pneumonia were considered in the initial diagnosis (Figure 1). On day 10, lumbar puncture and cerebrospinal fluid examination showed that the intracranial pressure was 228 mmH2O (reference range: 40-100 mm H2O), and the routine and biochemical abnormalities of cerebrospinal fluid were normal. Magnetic resonance imaging (MRI) on day 10 showed that bilateral fronto-parietal-temporal-occipital white matter and corpus callosum had symmetrical abnormal signals. The diagnosis is PRES (Figure 2). After pulse therapy with methylprednisolone (the dose was gradually reduced to oral prednisone), oxcarbazepine for anti-epileptics, and multiple other drugs and physical measures to treat fever, his limb activity, mental response, and eye gaze gradually improved. The episodes of convulsions also reduced. The burn wound healed on day 18 of admission. Intracranial pressure on lumbar puncture was 232 mmH2O on day 13 and 150 mmH2O on day 21; no other obvious abnormality was found in the cerebrospinal fluid test. Contrast-enhanced MRI performed on day 26 showed that there were multiple abnormal signals in the bilateral frontal, parietal, and occipital lobes, and the lesion range was smaller than that seen on the day 10 MRI. At this stage, PRES complicated with subacute late cerebral haemorrhage was considered. From day 27, the child had no fever, no right gaze, and no more convulsions, and his limb activities and mental reactions continued to improve further. Contrast-enhanced MRI on day 33 confirmed PRES combined with subacute late intracerebral haemorrhage; the haematoma was absorbed more than that seen in the previous MRI scan. We continued treatment with levetiracetam and piracetam for neuroprotection, oxcarbazepine for anti-epileptics, and oral prednisone to reduce cerebral oedema. On day 45 of hospitalization, the patient had no fever, convulsions, and right-eyed gaze; the fine movements of his hands improved; and he was discharged from the hospital. After discharge, oral prednisone (within 45 days after discharge) and oxcarbazepine (within 1 year after discharge) were continued to prevent epilepsy (Table 1). MRI performed 17 days after discharge showed that the multiple abnormal signals in the original bilateral frontal, parietal, and occipital lobes were significantly absorbed and reduced, and there were still softening foci in the bilateral frontal lobes, and most of the original bilateral frontal lobe and right occipital lobe haematoma had been absorbed. The right frontal lobe still had patchy chronic phase bleeding changes (Figure 3). CT performed 4 months after discharge showed bilateral frontal lobe softening foci (predominant on the right). The vital signs of the child were stable, and the limb movement and fine movements of the hands gradually improved. One year after discharge from the hospital, the child's limbs and fine movements were normal; he could walk, run, and jump normally; and he could speak in short and simple sentences.

posterior reversible encephalopathy syndrome, burn, child, magnetic resonance imaging (mri)

PMC9870721_01

Male

A 72-year-old male patient was admitted to the orthopedic department of our hospital for an ankle fracture after a traffic accident injury in May 2021, without any related medical history. He underwent an open reduction and internal fixation for a fracture of the medial lateral and posterior ankle diagnosed by x-ray (Figure 1). Because it was a posterior ankle fracture, the patient was placed in a prone position and a posterolateral approach incision from the ankle was made. Approximately 1.5 h after the operation, the patient suddenly complained of chest pain and dyspnea. He was assisted in turning over to the supine position and was given oxygen immediately; venous access was established by a central venous catheter (CVC). The patient's dyspnea did not improve, and his blood pressure dropped rapidly. His heartbeat stopped and cardiopulmonary resuscitation (CPR) was performed. A pulmonary embolism caused by a blood clot was first considered for the typical presentation of dyspnea, decreased blood pressure, chest pain, and oxygen saturation, and 1.5x106 U urokinase was administrated. The patient's heartbeat did not recover. During a pause in performing CPR, we decided to take a chest x-ray and found the right heart and pulmonary artery full of air; the increase in the light transmittance of the visual field in both lungs was consistent with the characteristics of a pulmonary embolism (Figure 2). Air was also drawn from the CVC; VAE was then considered based on the imaging results, and the patient was treated conservatively by positioning him head down and tilted to the left (Durant's position) The CPR was continued. The patient's heartbeat recovered, and his blood pressure rose to a normal level. He was still unconscious and sent to the intensive care unit. Unfortunately, the patient was discharged from the hospital and died 24 h later. We suspect the patient died due to anoxia or heart-related complications. However, no autopsy was performed.

case report, chest x-ray, esophageal ultrasound, prone position, venous air embolism

PMC5340051_01

Male

A 35-year-old-male patient presented with sudden loss of vision associated with periorbital swelling in both eyes (OU). He had systemic complaints of fever and pedal edema. The patient was already undergoing treatment for membranoproliferative glomerulnephritis, and for the previous seven months was taking oral prednisone (pg. mg/day) and Angiotensin converting enzyme inhibitor. Ocular examination revealed visual acuity of light perception (LP) with inaccurate ray projection in OU. Slit lamp biomicroscopic examination revealed 2+ cells in anterior chamber and pigments over the anterior lens surface in OU. Fundus examination revealed hazy media along with retinal detachment in the inferotemporal area in OU. Sub-retinal exudates, intraretinal hemorrhages along with dilated veins and narrowed arteries were visible. Intraocular pressure (IOP) was 16 mmHg in OU. The patient had blood pressure of 160/100 mmHg and bradycardia. Hence, the initial diagnosis was hypertension related exudative retinal detachment, although both atypical central serous chorioretinopathy and Vogt-Koyanagi Harada syndrome were also considered in differential diagnosis. After receiving a nephrologist's opinion, the patient was stabilized with an injection of hydrocortisone 200 mg OD, frusemide 40 mg OD, cefixime 200 mg BD along with amlodipine 5 mg OD as a hypertensive drug. After two days, the patient developed generalized hypotony, a staggering gait, truncal ataxia, and buccal and proximal weakness with decreased plantar reflexes. After neurology consultation, a pontomedullary lesion or cytomegalovirus meningitis was considered as an initial cause. A cerebrospinal fluid tap was performed to rule out meningitis; the results were normal. Magnetic resonance imaging (MRI) of the brain [Figure 1a and b] showed multiple cystic-enhancing lesions over both cerebral hemispheres, suggestive of tuberculomas or neurocysticercosis. The patient was started on anti-tubercular treatment (ATT) along with oral steroids. Four days after starting ATT, the patient had a generalized tonic-clonic seizure. A contrast MRI showed disseminated parenchymal lesions. At the beginning of anti-epileptic treatment, patient showed signs of improvement over the next two weeks; however after this period the patient started worsening. The patient had restricted abduction, sluggishly reacting pupils, 3+ cells in the anterior chamber OU with IOP of 66 and 52 mmHg in the right and left eyes, respectively. Fundus examination revealed increased exudates, increased height of retinal detachment and vitreous cells OU. A diagnosis of disseminated toxoplasma or malignancy was considered. Analysis of an aqueous tap via polymerase chain reaction (PCR) was negative for malignant cells, tuberculosis, cytomegalovirus (CMV), herpes simplex virus (HSV), varicella zoster virus (VZV), and toxoplasma. An Ahmed glaucoma valve was implanted in the left eye subsequent to failure of IOP control with maximum medical therapy. Postoperatively, the left eye was stony hard with severe conjunctival chemosis and a shallow anterior chamber [Figure 2]. Due to suspicion of metastatic endophthalmitis, five weeks after initial presentation, a vitreous biopsy was performed through pars plana vitrectomy. Intravitreal vancomycin (1 mg/0.1 ml), ceftazidime (2.5 mg/0.1 ml), and voriconazole (1 mg/0.1 ml) were instilled at the end of the procedure and the patient was started on fortified cefazolin 5% and tobramycin 1.4% every hour and Natamycin 5% (every six hours) for presumptive fungal endophthalmitis. All tissue sample smears and cultures that were tested for bacterial and fungal organisms were negative. Subsequently, the patient had no LP along with severe conjunctival chemosis, exposure keratopathy, and conjunctival abscesses. Cerebrospinal fluid was negative for CMV and Cryptococcus sp. Blood tests were negative for HIV and TORCH (Toxoplasma gondii, other viruses [HIV, measles, and so on), rubella [German measles]), CMV, and herpes simplex. Blood culture showed no evidence of bacterial and fungal organism growth. A bone marrow biopsy was performed to rule out blood cell malignancy but results were normal. Due to the progressive worsening of patients' systemic status and severe cachexia, a repeat MRI of the brain was done, and revealed a large right parieto-occipital mass lesion [Figure 1c and d]. The orbital region showed bilateral globe deformities, intraocular hemorrhages, and extraocular soft-tissue inflammation [Figure 1e and f]. A multiloculated intracerebral abscess was drained, and a brain biopsy was performed, revealing the presence of the Nocardia organism along with granulomatous reactions [Figure 3a-d]. The patient was administered intravenous imipenem for two weeks, amikacin for four weeks, and later, oral cotrimoxazole and trimethoprim. However, the patient had no LP in both eyes despite anti-nocardial treatment, probably because of delayed diagnosis and severity of involvement. Although the patient improved systemically over next two weeks, he subsequently developed phthisis of both eyes.

ahmed glaucoma valve, bilateral endogenous nocardial endophthalmitis, brain abscess, glomerulonephritis, membranoproliferative glomerulonephritis, ocular nocardiosis

PMC8766823_01

Female

A 37-year-old women, who underwent radical mastectomy for cancer of the left breast 1 week previously, visited the local hospital due to dizziness. After receiving symptomatic treatment, she experienced clinical deterioration, with lethargy, nausea, and vomiting, and she was unable to walk. There was no fever. Brain magnetic resonance imaging (MRI) showed abnormal intracranial signals in multiple areas. Four days later, she attended the neurology department of our hospital to check for intracranial metastases. A neurological examination revealed nuchal rigidity, eyes gazing to the right, loss of muscle strength in the left arm and leg (strength was 2/5 in both), and a positive Pap sign on the right. Other physical examinations revealed a dark red desquamation infection lesion (about 15 x 10 cm) on the left knee ( Figures 1A, B ). There was no medical history of severe infections, failure to thrive, eczema, chronic diarrhea, unexplained fevers, radiotherapy, or chemotherapy. She denied recent travel, any history of freshwater swimming, or consumption of uncooked meats or unpasteurized dairy products. However, she suffered trauma 2 years ago; she sustained a wound to the left lower limb after a fall near a garbage dump, which healed poorly. Six months previously, she developed a skin infection of the left limbs. Histopathological examination showed diffuse inflammatory cell infiltration of the dermis, with granuloma formation and multinucleate giant cells. Next-generation sequencing (NGS) revealed M. abscessus. A diagnosis of M. abscessus infection led to a combined therapy with rifampicin (450 mg, QD), ethambutol (0.75 g, QD), colabitol (500 mg, QD), and clarithromycin (500 mg, BID). Combined with the results of neurological examination and the presence of the skin lesion, a diagnosis of CNS M. abscessus infection was considered, and the previous therapy was continued. Mannitol infusion was instigated to reduce intracranial pressure. Analysis of the cerebrospinal fluid (CSF) revealed the following: karyocytes, 310/mul (8% neutrophilic granulocytes and 88% lymphocytes); red cells, 30/mul; protein, 1.515 g/L (normal range, 0.150-0.450 g/L); glucose, 1.7 mmol/L (normal range, 2.5-4.5 mmol/L); and chloride, 115 mmol/L (normal range, 120-131 mmol/L). Intracranial pressure was 330 mmH2O. Routine laboratory values, including a complete blood count, procalcitonin, and C-reactive protein, were within normal limits. Microscopic examination with India ink staining, bacterial and Mycobacterium tuberculosis cultures, and cerebrospinal cytology were all negative. Brain MRI revealed multifocal enhanced mass-like lesions (in the right temporal lobe, right thalamus, left parahippocampal gyrus and pontine, and fourth ventricle) with enhancement and edema. Her condition continued to worsen and she developed headache, fever, and somnolence. Neurological examination showed that the muscle strength in the right limbs had weakened further. After consultation with infectious disease specialists, she received isoniazid (0.3 g, QD), pyrazinamide (500 mg, TID), and linezolid (600 mg, Q12H) to treat suspected M. abscessus infection. On day 9 of hospitalization, she was transferred to the ICU after tracheal intubation due to deterioration of consciousness (GCS = 10 points) and decreased oxygenation. Emergency brain CT revealed dilated ventricles and reduced brainstem density. We performed left lateral ventricular drainage, a routine microscopic examination (including India ink staining), bacterial and M. tuberculosis cultures, and cerebrospinal cytology; all were negative. Fortunately, NGS identified B. mandrillaris ( Figures 2A, B ). Based on the available information, including the specific NGS outcome, the history of trauma, and the skin lesion, she was diagnosed with GAE caused by B. mandrillaris. She was treated with amphotericin B (40 mg, QD), flucytosine (500 mg, TID), fluconazole (800 mg, QD), sulfamethoxazole and trimethoprim (1.44 g, QID), clarithromycin (500 mg, QD), pentamidine (300 mg, QD), and intravenous immunoglobulin (20 g, QD). During treatment, her lymphocyte count and immune cell subpopulations were within the normal range. To test the ability of T cells to recognize infections, we performed T-cell receptor (TCR) sequencing using peripheral blood and CSF samples. The Top1 TCR in the CSF sample showed high clonal proliferation ( Figures 3A, B ), with a cloning frequency of 15%; the same CDR3 amino acid (AA) sequence CASNRGAENYGYTF was also detected in the peripheral blood, although with a frequency of 3.77E-06 ( Figure 3C ). At the same time, we compared the TCR diversity in the CSF and peripheral blood. The TCR diversity in the CSF was significantly lower than that in peripheral blood ( Figure 3D ), which may be related to the lower number of lymphocytes in the CSF. On day 15 post-admission, the patient's consciousness deteriorated further, with a GCS score of 1+T+1, and brain MRI showed that the multifocal enhanced mass-like lesions were more numerous than before ( Figures 4A-D ). MRI of the cervical thoracic segment revealed that the spinal cord functioned naturally, with punctate and patchy longer T2 signals, which were vaguely enhanced ( Figure 4E ). Balamuthia encephalomyelitis was diagnosed, and she was treated with intrathecal injection of amphotericin B and miltefosine (50 mg, TID) on hospital day 16. However, she experienced rapid clinical deterioration and spontaneous breathing stopped. On day 27 post-admission, the woman's family requested a transition home to allow a natural death.

balamuthia mandrillaris, t-cell receptor, encephalitis, encephalomyelitis, next-generation sequencing

PMC4841938_01

Female

A 24-year-old Asian female patient was admitted to our hospital, with left ear fullness and otorrhea. At an outpatient clinic, she was previously diagnosed with otitis media with effusion (OME) that was unresponsive to a three-week course of antibiotics. Otoscopic examination revealed perforation of the tympanic membrane and profound amber-colored discharge, behind the eardrum (Figure 1A). On physical examination, no palpable neck lymph nodes were noted. Routine hematologic examination revealed normal erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels. Initial ear culture studies did not identify any pathogens. After one week of further antibiotic medication, she underwent ventilation tube (V-tube) insertion to maintain aeration of the middle ear and prevent fluid reaccumulation. However, the presence of purulent discharge from the V-tube was again noted on the third follow-up visit (Figure 1B). At this visit, the patient also presented with new-onset ipsilateral facial nerve palsy. Facial paralysis was identified as grade IV, using the House-Brackmann grading system, due to presence of incomplete eye closure and mouth drooping, with maximum effort. She was then hospitalized for further evaluation. After hospitalization, the patient underwent a flexible nasopharyngoscopy, which revealed a polypoid mass, with severe inflammation, in the roof of the nasopharyngeal wall. Extensive purulent granulation tissue was also noted, along the left posterolateral nasopharyngeal wall (Figure 2). A biopsy was taken from the polypoid mass of the nasopharyngeal roof. The chest radiography was normal (Figure 3). The patient had no underlying disease, no history of pulmonary TB or contact with TB patients. Because the patient had no pulmonary symptoms and the chest radiography was normal, we excluded primary pulmonary TB. We did not perform sputum acid-fast bacilli (AFB) staining. The computed tomography (CT) examinations were performed using a 64 channel multi-detector computed tomography (MDCT) (Brilliance 64, Philips Medical System, Cleveland, OH, USA) or 16 channel MDCT (Light Speed, GE Healthcare, Milwaukee, WI, USA) with intravenous administration of contrast medium (iohexol, Omnipaque 350 mg, GE Healthcare, Milwaukee, WI, USA). Magnetic resonance (MR) examinations were performed using a 3.0-T MR system (Intera Achieva 3.0-T; Philips Medical Systems, Best, the Netherlands) with intravenous administration of a total volume of 15 mL contrast medium (gadoteridol, ProHance, Bracco Diagnostics Inc., Princeton, NJ, USA). Contrast-enhanced CT and MR of the paranasal sinuses showed a polypoid mass, with necrotic foci, at the roof of the nasopharyngeal wall (Figure 4A and B). It also revealed diffuse mucosal enhancement and low attenuated polypoid masses, obliterating the left torus tubarius and pharyngeal opening of the Eustachian tube (Figure 5A and B). Unenhanced temporal CT showed fluid filled middle ear cavity, mastoid antrum and mastoid air cells, without sclerotic changes (Figure 6). Contrast-enhanced temporal MRI showed avid enhancement at the canalicular, labyrinthine, anterior genu, tympanic and mastoid segments of the left facial nerve, which confirmed left facial neuritis (Figure 7). Histopathology of the biopsy specimen, taken from the nasopharyngeal roof and mastoid antrum confirmed caseating granulomatous inflammation, consistent with TB (Figures 8 and 9). However, the specimen from the nasopharyngeal mass showed negative in AFB staining and polymerase chain reaction (PCR) tests. Considering the low sensitivity of AFB smear and PCR in extrapulmonary specimens, the results from this case report were not unusual. We have reached final diagnosis of primary nasopharyngeal and middle ear TB, on the basis of clinical, radiologic and histopathologic examination, against those from cytology and microbiology examination. The patient was started on four antituberculous medications (rifampicin, isoniazid, pyrazinamide and ethambutol) and underwent left canal wall up (CWU) mastoidectomy, with tympanoplasty. During the operation, multiple polypoid masses were observed in the entire middle ear cavity, mastoid antrum and mastoid air cells. In addition, the pharyngeal opening of the Eustachian tube was obstructed by polypoid masses. All ossicles were surrounded by granulation tissue and an ossiculoplasty was performed. Furthermore, bony canal dehiscence was noted, at the tympanic segment of the facial nerve, and surgical decompression was performed, as well. Histopathology of the biopsy specimens taken from the middle ear cavity and mastoid antrum during the operation also confirmed caseating granulomatous inflammation, consistent with TB. Electrodiagnostic testing, needle electromyogram and nerve conduction studies, were performed three weeks after the operation, which revealed the remaining left facial neuropathy.

facial nerve, mastoiditis, nasopharyngeal diseases, paralysis, tuberculosis

PMC9796209_01

Female

We report monkeypox virus infection in a 22-year-old woman with no remarkable medical history who sought care at the Kings County Hospital Center (Brooklyn, NY, USA) emergency department with numerous painful vulvar and intravaginal lesions. The patient reported a sexual encounter with 1 male partner 2.5 weeks before. She reported that they had vaginal sex and noted that her partner had a few dark bumps on his penis that resembled ingrown hairs. It was unknown if this partner had any sexually transmitted infections. Two weeks after the encounter, the patient experienced onset of myalgias, fatigue, and fever. Two days after the onset of fever, she first noticed 3 mildly painful flesh-colored bumps, which progressed the following day and became white in color and more numerous. The lesions prompted the patient to go to the emergency department at an outside hospital. At arrival, the patient was febrile to 100.7 F. She underwent screening for sexually transmitted infections, including testing for monkeypox. She was discharged home with prescriptions of lidocaine, bacitracin, and ibuprofen as needed for pain while laboratory results were pending. On day 3 after the lesions first appeared, they became larger and more painful, to the point of causing substantial distress when the woman sat, and had spread toward her perianal region. On day 4 after the lesions' appearance, the woman could no longer tolerate the pain and went to the emergency department at Kings County Hospital Center. At arrival, her temperature was 98.4 F, heart rate was 63 beats/min, respiratory rate was 18 breaths/min, and blood pressure was 118/72 mm Hg. Gynecologic examination revealed numerous singular, raised lesions that were umbilicated, ulcerated, vesicular, papular, and pustular, in different stages (Figure). The right labia majora was erythematous without any induration or fluctuance. We observed no lymphadenopathy on examination to the inguinal regions bilaterally. The vagina and cervix appeared normal otherwise. The uterus was small and mobile, and we noted no adnexal masses or tenderness. We observed no cutaneous lesions elsewhere in the body. Results of heart, lung, abdominal, and neurologic examinations were unremarkable. The patient was tested for gonorrhea, chlamydia, HIV, herpes simplex virus, syphilis, and monkeypox. The patient also underwent a vulvar biopsy because the gynecology team was unfamiliar with the type of genital lesions she was experiencing. While waiting for the test results, the patient was informed by her male partner that he had tested positive for monkeypox virus earlier that day. The patient was admitted to the hospital and began a 14-day course of tecovirimat (600 mg every 12 h) with accompanying isolation precautions for 21 days as per the recommendations of the physicians within Kings County Hospital's Infectious Disease department. All results of laboratory tests were negative except for a positive PCR result for monkeypox virus. The patient continued inpatient treatment with tecovirimat and was discharged on hospital day 3 without experiencing any other complications. Approximately 10 days after the onset of lesions, the patient reported in a follow-up telehealth visit that the lesions were decreasing in size and scabbing over and that the pain had greatly subsided. Perineal, vaginal, and cervical lesions in women have rarely been described in the literature in the setting of a monkeypox infection. Furthermore, most cases documented from the 2022 monkeypox outbreak have primarily studied male genital lesions, with little to no mention of the clinical manifestations of monkeypox virus in female genitalia. In a literature search, we found a single case report documenting genital monkeypox lesions in a woman. In that case report, the patient experienced itchy, but painless, genital lesions extending down her labia majora that developed a week and a half after sexual intercourse with a new male partner. This patient also had a 2-day history of fever and myalgias. This patient's lesions and symptoms were similar to those of our patient's. More research must be performed on the clinical manifestations of monkeypox, which would clarify the disease progression and help clinicians identify and diagnose this infection and properly treat patients. Monkeypox should be considered in the differential diagnosis of patients with genital lesions, especially in persons who are sexually active. Furthermore, there has been little study of how monkeypox virus manifests in women, especially during pregnancy, even though >400 cases have been reported in women in the United States in 2022 alone. Further consideration could elucidate the long term sequalae of monkeypox and its implications for health conditions such as pelvic inflammatory disorder, infertility, and cancer, which can occur with other sexually transmitted infections.

new york, united states, monkeypox, sexually transmitted infections, viruses, zoonoses

PMC3992218_01

Female

A 60-year-old Caucasian woman presented to our care with shortness of breath with exertion, which was relieved by rest for 2 weeks. She initially went to her primary care physician, who noted that the patient was hypoxic with oxygen saturations at 73%. She was therefore sent to the emergency department for further evaluation. Other complaints included intermittent substernal chest pain of moderate intensity with radiation to the back of the neck and a productive cough with white phlegm, but no blood was noted. She denied any fever, chills, nausea, vomiting, headaches, dizziness, abdominal pain, or diarrhea. Her comorbidities included hypertension and hypothyroidism. Home medications were levothyroxine 112 mcg tab daily and hydrochlorothiazide 12.5mg tab daily. She quit smoking tobacco about 3 years ago but previously had smoked 1/2 pack per day for 10 years. Initial vital signs were significant for hypertension (blood pressure: 155/81) and hypoxia (oxygen saturation was 70% on room air). She was then placed on 3 liters of oxygen through nasal cannula; oxygenation then increased to 94%. The only significant physical examination findings were bilateral diffuse wheezing upon auscultation of the lungs. The initial laboratory workup (Table 1) was only significant for elevated liver enzymes. A chest radiograph (Figure 1) showed mild cardiomegaly with increased parahilar vascularity suggestive of pulmonary edema. Computed tomography (CT) angiogram (Figure 2) of the chest was ordered to rule out pulmonary embolism. It revealed a diffuse bilateral ground glass density in the lung parenchyma with intervening normal appearing lung parenchyma having a mosaic attenuation pattern. Diffuse micronodules throughout both lungs were also noted. 2D echocardiogram showed a borderline left atrial enlargement and left ventricle ejection fraction of 70+-5%. Our differential diagnosis after our initial assessment and imaging studies was hypersensitivity pneumonitis, sarcoidosis, miliary tuberculosis, bacterial pneumonia, and lung malignancy. We suspected hypersensitivity pneumonitis as the most likely diagnosis but were unsure of the cause. On further questioning, the patient explained that she worked as a server at a restaurant located on a ranch approximately 35 miles east of El Paso, Texas. This ranch has several different species of farm animals, including birds (ducks and geese), cattle, and horses. She explained that she did not have actual close exposure to the animals or the birds. However, she had been collecting the feathers of the ducks and geese nearby the restaurant for the past 6 months and placed them in a vase on her kitchen table at home. She did not have any pet birds or birds living outside the house. No other possible environmental exposures were noted. On the 3rd hospital day, a bronchoscopy was done that showed anatomically normal airways with diffusely erythematous mucosa and clear secretions. Bronchoalveolar lavage (BAL) of the right middle lobe was negative for malignancy, pneumocystic carinii, fungi, or granulomas. The BAL fluid was hazy and red, the cell analysis included a red blood cell count of 5000 cells per mm3 and white blood cell count was 1968 cells per mm3 with neutrophils accounting for 90%, lymphocytes of 6% and monocytes 4%. Cultures of BAL were negative for any microorganism growth, acid fast bacilli or fungi. The pulmonary function tests (PFTs) showed a proportional decrease in both FEV1 and FVC, leading to a decreased FEV1/FVC ratio. The carbon monoxide diffusing capacity (DLCO) was also decreased, suggesting a restrictive lung disease process. The human immunodeficiency virus (HIV) test result was negative. The absolute CD4 was 1272 cells/mcL (490-1740 cells/mcL), absolute CD8 count was 652 cells/mcL (180-1170 cells/mcL), and the CD4/CD8 ratio was 1.95 (0.86-5.0). Transbronchial lung biopsy revealed non-caseating granulomas, aggregates of epithelioid macrophages, and patchy mononuclear cell infiltration with lymphocytes and fibrotic tissue. The patient clinically improved and was discharged home on the 6th hospital day with prednisone 20 mg daily. At her 1-month follow-up with the pulmonologist after discharge, she still worked at the restaurant on the ranch, but had minimal exposure to the birds and no longer collected bird feathers. The chest CT (Figure 3) findings were unchanged from previous imaging evaluation. The chest CT findings were diffuse bilateral geographic mosaic attenuation and bilateral centrilobular/peribronchial pulmonary nodules, likely representing granulomas, measuring up to 7 mm and scattered throughout both lungs. There was also subcentimeter bilateral upper/lower paratracheal, and subcarinal and hilar lymph node enlargement. She was on home oxygen and prednisone 20 mg daily. She explained that she no longer had any shortness of breath, but on physical examination mild diffuse wheezing was present bilaterally. The PFTs still had a proportional decrease in both FEV1 and FVC with a decreased FEV1/FVC ratio, but improved from the last PFTs and the DLCO was also improved. Since the patient was doing well, we initiated a prednisone taper over the course of 1 month. Additional chest CT and PFTs were performed at the 6-month follow-up visit, without any interval improvement. At this time she was no longer using the home oxygen and was tapered off the prednisone. She was asymptomatic and no wheezing was noted on auscultation of the lungs.

alveolitis, bird fancier’s lung, bird feathers, extrinsic allergic

Chest CT: diffuse bilateral ground glass density in the lung parenchyma with intervening normal appearing lung parenchyma having a mosaic attenuation pattern.

PMC3992218_01

Female

A 60-year-old Caucasian woman presented to our care with shortness of breath with exertion, which was relieved by rest for 2 weeks. She initially went to her primary care physician, who noted that the patient was hypoxic with oxygen saturations at 73%. She was therefore sent to the emergency department for further evaluation. Other complaints included intermittent substernal chest pain of moderate intensity with radiation to the back of the neck and a productive cough with white phlegm, but no blood was noted. She denied any fever, chills, nausea, vomiting, headaches, dizziness, abdominal pain, or diarrhea. Her comorbidities included hypertension and hypothyroidism. Home medications were levothyroxine 112 mcg tab daily and hydrochlorothiazide 12.5mg tab daily. She quit smoking tobacco about 3 years ago but previously had smoked 1/2 pack per day for 10 years. Initial vital signs were significant for hypertension (blood pressure: 155/81) and hypoxia (oxygen saturation was 70% on room air). She was then placed on 3 liters of oxygen through nasal cannula; oxygenation then increased to 94%. The only significant physical examination findings were bilateral diffuse wheezing upon auscultation of the lungs. The initial laboratory workup (Table 1) was only significant for elevated liver enzymes. A chest radiograph (Figure 1) showed mild cardiomegaly with increased parahilar vascularity suggestive of pulmonary edema. Computed tomography (CT) angiogram (Figure 2) of the chest was ordered to rule out pulmonary embolism. It revealed a diffuse bilateral ground glass density in the lung parenchyma with intervening normal appearing lung parenchyma having a mosaic attenuation pattern. Diffuse micronodules throughout both lungs were also noted. 2D echocardiogram showed a borderline left atrial enlargement and left ventricle ejection fraction of 70+-5%. Our differential diagnosis after our initial assessment and imaging studies was hypersensitivity pneumonitis, sarcoidosis, miliary tuberculosis, bacterial pneumonia, and lung malignancy. We suspected hypersensitivity pneumonitis as the most likely diagnosis but were unsure of the cause. On further questioning, the patient explained that she worked as a server at a restaurant located on a ranch approximately 35 miles east of El Paso, Texas. This ranch has several different species of farm animals, including birds (ducks and geese), cattle, and horses. She explained that she did not have actual close exposure to the animals or the birds. However, she had been collecting the feathers of the ducks and geese nearby the restaurant for the past 6 months and placed them in a vase on her kitchen table at home. She did not have any pet birds or birds living outside the house. No other possible environmental exposures were noted. On the 3rd hospital day, a bronchoscopy was done that showed anatomically normal airways with diffusely erythematous mucosa and clear secretions. Bronchoalveolar lavage (BAL) of the right middle lobe was negative for malignancy, pneumocystic carinii, fungi, or granulomas. The BAL fluid was hazy and red, the cell analysis included a red blood cell count of 5000 cells per mm3 and white blood cell count was 1968 cells per mm3 with neutrophils accounting for 90%, lymphocytes of 6% and monocytes 4%. Cultures of BAL were negative for any microorganism growth, acid fast bacilli or fungi. The pulmonary function tests (PFTs) showed a proportional decrease in both FEV1 and FVC, leading to a decreased FEV1/FVC ratio. The carbon monoxide diffusing capacity (DLCO) was also decreased, suggesting a restrictive lung disease process. The human immunodeficiency virus (HIV) test result was negative. The absolute CD4 was 1272 cells/mcL (490-1740 cells/mcL), absolute CD8 count was 652 cells/mcL (180-1170 cells/mcL), and the CD4/CD8 ratio was 1.95 (0.86-5.0). Transbronchial lung biopsy revealed non-caseating granulomas, aggregates of epithelioid macrophages, and patchy mononuclear cell infiltration with lymphocytes and fibrotic tissue. The patient clinically improved and was discharged home on the 6th hospital day with prednisone 20 mg daily. At her 1-month follow-up with the pulmonologist after discharge, she still worked at the restaurant on the ranch, but had minimal exposure to the birds and no longer collected bird feathers. The chest CT (Figure 3) findings were unchanged from previous imaging evaluation. The chest CT findings were diffuse bilateral geographic mosaic attenuation and bilateral centrilobular/peribronchial pulmonary nodules, likely representing granulomas, measuring up to 7 mm and scattered throughout both lungs. There was also subcentimeter bilateral upper/lower paratracheal, and subcarinal and hilar lymph node enlargement. She was on home oxygen and prednisone 20 mg daily. She explained that she no longer had any shortness of breath, but on physical examination mild diffuse wheezing was present bilaterally. The PFTs still had a proportional decrease in both FEV1 and FVC with a decreased FEV1/FVC ratio, but improved from the last PFTs and the DLCO was also improved. Since the patient was doing well, we initiated a prednisone taper over the course of 1 month. Additional chest CT and PFTs were performed at the 6-month follow-up visit, without any interval improvement. At this time she was no longer using the home oxygen and was tapered off the prednisone. She was asymptomatic and no wheezing was noted on auscultation of the lungs.

alveolitis, bird fancier’s lung, bird feathers, extrinsic allergic

Chest CT: diffuse bilateral geographic mosaic attenuation and bilateral centrilobular/peribronchial pulmonary nodules.

PMC9109900_01

Male

A 32-year-old male who presented with headache, dizziness, nausea, and vomiting was admitted to local hospital in October 2018. Two days later, he was diagnosed with HIV. He had a history of male sexual partners. His CD4 cell count and plasma HIV load were 15 cells/muL and 14,900 copies/mL, respectively. On physical examination, he had a body temperature (T) of 37.3 C, blood pressure (BP) of 113/50 mmHg, pulse (P) of 105 beats per minute (bpm), and respiration rate (R) of 20 breaths/min. Moreover, he had a stiff neck, positive meningeal irritation sign, and oral candidiasis. A lumbar puncture and cerebrospinal fluid (CSF) analysis was performed; he had an intracranial pressure (ICP) of >400 mmH2O, a CSF white blood cell (WBC) count of 50 cells/muL, neutrophils of 14%, glucose of 1.4 mmol/L, protein of 0.56 g/L, chlorine of 116 mmol/L, and CSF: serum glucose ratio of 0.33. India ink staining of the CSF revealed Cryptococcus, and CSF culture showed Cryptococcus neoformans. Brain imaging of computed tomography (CT) was unremarkable. Based on these findings, he was diagnosed with CM. Ventriculoperitoneal (VP) shunting to release the increased intracranial pressure was performed one week after his admission. He received antifungal therapy for 2 weeks (amphotericin B [0.7 mg/kg/day] and 5-flucytosine [100 mg/kg/day]), followed by consolidation with fluconazole (400 mg/day) for 8 weeks. After 14 days of antifungal therapy, the culture for Cryptococcus was negative. On day 28 of admission, highly active ART (HAART; lamivudine+ Tenofovir disoproxil fumarate +lopinavir/ritonavir) was initiated, and he was discharged from the hospital. After the discharge, the patient was followed up regularly and continued anti-Cryptococcus and ART treatment without obvious symptoms. From August 2019 to March 2020, the patient was hospitalized in the local hospital due to repeated headaches, fever, and convulsions. His CD4 count gradually increased to 131 cells/muL, the HIV viral load decreased to undetectable level, ICP was between 150 and 220 mmH2O, CSF WBC count was 15-50 cells/muL, CSF glucose was between 2.2 and 2.3 mmol/L, and CSF: serum glucose ratio was between 0.43 and 0.53. The CSF protein increased up to 12.625 g/L at October 2019, no Cryptococcus was found in India ink staining, the CSF Cryptococcus antigen was positive, and Cryptococcus culture was negative. He was treated at local hospitals with dexamethasone of 5-10 mg QD for 10 days, and the dosage was then reduced gradually. The same anti-Cryptococcus and ART treatment were continued. The patient's headache improved, and he was discharged from the hospital with methylprednisolone (4 mg/day) for 2 weeks. In May 2020, although an undetectable plasma viral load and CD4 count of 122 cells/muL, the patient's reactions were more sluggish at our hospital (the First Affiliated Hospital of Zhejiang University, China). On physical examination, he had a T of 36.9 C, BP of 111/79 mmHg, P of 108 bpm, and R of 18 breaths/min. He was well oriented, responded to questions slowly, and had a negative meningeal irritation sign. CSF analysis revealed an opening pressure of 150 mmH2O, WBC count of 120 cells/muL, glucose of 2.1 mmol/L, total protein level of 7.89 g/L, and CSF: serum glucose ratio was 0.41. Furthermore, no Cryptococcus was found in India ink staining, the CSF Cryptococcus antigen was positive, and Cryptococcus culture was negative. Culture and polymerase chain reaction testing for Epstein-Barr virus, cytomegalovirus, and herpes simplex virus-1 and -2 were negative. A T-SPOT test for Mycobacterium tuberculosis in blood was negative. Further, acid-fast staining of a sputum smear and the CSF culture for bacteria and fungi were negative. However, multiple intracranial lesions with meningeal enhancement were observed in brain magnetic resonance imaging (MRI) (Figure 1A). On admission, the patient's Montreal Cognitive Assessment (MoCA; Beijing version; cut-off score, 26) and International HIV Dementia Scale (IHDS; cut-off score, 10) scores were 13 and 2.5, respectively. Although he was on standard anti-cryptococcal treatment and HAART, he had aseptic meningitis with cognitive impairment; he was diagnosed with paradoxical IRIS. After providing written informed consent, he received oral lenalidomide (one cycle: 25 mg/day for 21 days and no lenalidomide for 7 days according to the manufacturer's instructions) simultaneously with fluconazole and HAART. The patient was followed up at 0, 1, 2, 3, 6, and 12 cycles after lenalidomide treatment initiation. Blood tests (blood routine, liver function, kidney function, blood lipid, serum glucose, electrolyte, coagulation function, CD4 count, HIV viral load) and CSF examinations (CSF routine, biochemistry, culture, India ink staining, Cryptococcus antigen detection, Cryptococcus culture) were performed during each follow-up. Neuroimaging and cognitive evaluations were performed at baseline,1, 2, 6, and 12 cycles. Plasma and CSF samples were stored at -80 C for testing. One cycle after this treatment, his headache was relieved, his cognitive function had recovered rapidly (MoCA and IHDS scores increased to 20 and 6.5, respectively), and he was able to communicate normally. CSF testing revealed a WBC count of 50 cells/muL, glucose of 1.9 mmol/L, CSF: serum glucose was 0.42 and total protein level of 1.64 g/L, which suggested an inflammation. Furthermore, CSF cultures were negative. After 6 cycles of lenalidomide therapy, his cognitive status returned to normal (MoCA and IHDS scores increased to 26 and 11, respectively). The CSF WBC count (14 cells/muL) and total protein levels (0.55 g/L) were reduced, and CSF cultures were negative. T2-weighted MRI revealed a significant reduction in the signal in the left frontal lobe lesion (Figure 1B). Lenalidomide treatment was terminated after 12 cycles, and the patient was followed up for 18 months. There were no abnormalities in the routine blood tests, liver and kidney function tests, and myocardial zymogram. As of the time of this report, he has remained asymptomatic and has resumed his normal duties.

cryptococcus, acquired immune deficiency syndrome, cognition, immune reconstitution inflammatory syndrome, immunomodulator

PMC9803297_01

Unknown

Globally, approximately 38 million people were living with the human immunodeficiency virus (HIV) in 2019. Of these, 36.2 million were adults, and 1.8 million were children (<15 years old). Most people living with HIV are from low-and middle-income countries: 20.7 million people (54%) in eastern and southern Africa. The number of people who died of AIDS has declined over the years due to improving access to Antiretroviral therapy (ART). ART is the daily use of a combination of medicine called "HIV regimen" to stop the virus from multiplying and can suppress it to undetectable levels in the blood. The initial standard treatment for people newly diagnosed with HIV generally includes three antiretroviral drugs from at least two different HIV drug classes. HIV treatment access is key to the global effort to end acquired immunodeficiency syndrome (AIDS) as a public health threat. By the end of 2019, 25.4 million people with HIV (67%) were accessing ART globally. The Joint United Nations Programme on HIV/AIDS (UNAID) planned that 90% of all people who know their status should be on ART. However, 12.6 million people did not access the treatment. According to the 2018 estimate, 613,000 Ethiopians were living with HIV. However, only 436,000 individuals have received the treatment. Ethiopia is a low-income country experiencing a high number of patients with HIV/AIDS. In response to HIV/AIDS, Ethiopia introduced the ART program to save lives, restore mental and physical functions, and improve the quality of life of people living with HIV/AIDS. The first adult treatment guideline was issued in 2003 and revised in 2005, 2007, 2014, and 2018. A pediatric treatment guideline was also developed and consolidated with the adult guidelines in 2007. The availability of HIV-related preventive care and treatment services is essential to reduce the burden of the disease. The treatment is aimed at early case detection through testing services, care, support, adherence surveillance, and monitoring. However, many resource-limited countries face challenges in availing of services. A well-functioning ART center needs a separate area for advisory services with appropriate privacy rooms. In India, the assessment of ART centers showed less than half of the facilities (48%) had ideal counseling areas and education and communication materials. The study on the availability of HIV testing, care, and treatment in Ghana revealed viral load and early infant diagnosis, and laboratory testing services were reported at 5.8% and 13.4%, respectively. Shortage of test kits, drugs, and job training were the challenges of various facilities. The study conducted in South Africa showed that the service quality of ART clinic counselors often fails to address HIV prevention. The healthcare provider performed TB symptom screening for only 41.1% of visitors. A study from the 2014 Service Provision Assessment (SPA) survey revealed the capacity of health facilities for HIV/AIDS care was poor. For instance, out of the 873 health facilities, 32.6%, 53.7%, and 74.5% of health facilities providing ART, prevention of mother-to-child transmission (PMTCT), and HIV counseling and testing (HCT) service, respectively. The overall capacity scores were 45% for health centers and 77.1% for hospitals. Nearly one-third and a quarter of the health centers provided HCT and ART services using national guidelines. Antiretroviral drugs, baseline CD4 count or viral load, and tuberculosis (TB) screening were available in less than 50% of the health centers. Other studies also revealed that inputs for services such as drugs were not available adequately. Moreover, studies on client satisfaction with ART service ranged from 55.2% to 89.6%. Different factors affect client satisfaction, such as income, age, marital status, educational status, distance, occupation, availability of drugs, patient-client interaction, and communication. The process evaluation conducted on pediatric ART service in Addis Ababa revealed the overall compliance of healthcare providers to the national guideline of ART service was 81.6%. The evaluation of HIV/ AIDS quality care in Bahir Dar Felege Hiwot referral hospital showed that among patients eligible for ART per the national guidelines, only 205 (76.8%) took ART. In comparison, 34 (12.7%) never started ART, and the remaining 28 (10.5%) failed to continue treatment after initiation. Previous studies only focused on client satisfaction or the availability of materials. A comprehensive and systematic assessment of different program dimensions is essential to make evidence-based decisions for program improvement. Pediatric antiretroviral treatment failure and viral load are high despite the existing treatment. Therefore, the evaluation of the implementation of pediatric ART services is crucial. As to the authors' knowledge, there is no evaluation conducted in Ethiopia about pediatrics' ART implementation status in the health center (HC) setup. Therefore, this evaluation is designed to assess the availability of resources required to provide pediatric ART services effectively, assess the compliance of HCPs with the national guideline in delivering pediatric ART services and determine the level of caregiver satisfaction with ART services provided and identify factors associated with the satisfaction of caregivers/mothers. Moreover, the evaluation results could be used for pediatric ART service improvement and to make evidence-based decision-making. The evaluation's finding is significant to the public, government, and stakeholders.

PMC3754408_01

Male

A 12-year-old boy presented with complaints of fever and cough occurring on and off for 2 years. The child was diagnosed as empyema by the local physician and an intercostal drain was inserted which drained minimal foul smelling fluid. The drain was apparently retained for 3 months in view of persistent discharge and child was treated with anti-tubercular therapy for 9 months. For last 6 months, he complained of progressive dyspnoea, not associated with any postural variations. He had a sinus in the chest which was persistently draining 5-10 ml of foul smelling fluid daily. He had a history of significant weight loss and decreased appetite for 6 months. There was no history of contact with tuberculosis in the family. On examination he was found to be wasted with severe acute malnutrition. General physical examination revealed severe pallor with grade III clubbing. Respiratory system examination revealed a bulging chest on the right side with decreased movements. The same areas were found to be dull on percussion. Bronchial breathing was present in the right infraclavicular and interscapular regions. All the other systems were within normal limits. Chest X ray (Fig. 1) showed a homogenous opacity on the right side with a fluid level, with clear costophrenic angles. Calcification was noted in the right 6th intercostal spaces with crowding of ribs in the upper zones. USG chest showed evidence of minimal (1.4mm) loculated collection in right posterior basal region. CT chest (Fig. 2) done revealed a well circumscribed peripherally enhancing multiloculated cystic fluid and a soft tissue density lesion with fat components, well defined multiple calcified tooth like structures and bone pieces. There were associated patchy sub-segmental non homogenous opacities in apical and posterior segment of right upper lobe. Multiple small non-calcified, non-necrotic right paratracheal, pre-tracheal and subcarinal lymphadenopathy were noted. The cultures from the sinus tract grew pseudomonas aeruginosa and serratia marcescens sensitive to ceftazidime and amikacin. The patient thus received a course of antibiotics for 2 weeks. The fever subsequently subsided. Serum alpha protein levels were within normal limits. A right sided thoracotomy was done and tumour was excised en-bloc. A white-gray colored, well circumscribed, and thick capsulated mass was removed. No communication between the bronchi and the mass were noted. The teratoma was found to be originating from the posterior mediastinum (Fig. 3). A tube thoracostomy was left, the collapsed right lung was re-expanded, and the patient was extubated. Postoperative course remained uneventful. Gross pathological examination showed a 10x6x3 cm mass with 2 skin covered nodules with grey yellow (fatty) and bony hard areas within focally cystic areas on cut section. Histopathological examination showed areas of fat, bone, teeth and lung tissue with normal skin tissue on the covering and with occasional neural tissue present, suggestive of a mature teratoma.

empyema thoracic, infected teratoma, mediastinum

PMC2994881_01

Female

A 40-year-old Indian woman presented with progressively increasing vulval swellings over a period of five years. She also described a loss of appetite and weight. There was a history of fever with a rise in the evenings, night sweats and vaginal discharge, although her menstrual periods were normal. Eight years prior to presentation, she had generalized lymph node tuberculosis with discharging cervical and inguinal sinuses, for which she received a full course of anti-tubercular therapy. Her tuberculosis was completely cured by the anti-tubercular therapy and she did not show any evidence of a recurrence. Her genital swellings were extremely large and caused her to experience difficulty in walking. Sexual intercourse was not possible. Our examination revealed that she was poorly nourished, with a marked pallor. There was no lower limb edema. She had two giant vulval swellings measuring 35 x 25 cm on the right side and 45 x 30 cm on the left side (Figure 1 and 2). In the standing position, the left vulval swelling extended below her knees. While walking, she had to tuck the swellings between her buttocks. The skin overlying the swellings was thick and rugose. Both her inguinal and cervical regions had puckered scars of healed sinuses without any palpable lymph node. The rest of our physical examination, including her vaginal wall, chest and abdomen was normal. She was found to be severely anemic (Hb 6 gm%) with a normal leucocyte count. Our other investigations, including blood urea nitrogen, serum electrolytes, creatinine, Mantoux test, night blood smear, chest X-ray, ultrasonography of her abdomen and pelvis, and pap smear were normal. She was taken up for surgery after the correction of her anemia. A wide local excision with a primary closure was performed. Part of the fibro-fatty tissue of her labia majora was preserved to give them a natural bulging appearance (Figures 2, 3, 4, 5). There was considerable oozing of lymph during surgery and in the post-operative period, but healing occurred with primary intention. The swellings removed from her right and left labia weighed 20 lb and 16 lb respectively. The immediate post-operative period was uneventful. Nearly six years of follow up revealed a satisfactory recovery, although in the immediate post-operative period and in the early follow-up period she presented with seroma formation under the skin flaps that was managed by aspiration and pressure bandaging. She also experienced episodes of serous discharge from the site that was self limiting and was managed by pressure bandaging.

PMC2994881_02

Female

A 27-year-old Indian woman presented to our hospital with a very similar history and findings to that of case report 1, although her swellings were not as large. She presented with progressively increasing vulval swellings over a period of four years. She had a past history of fever, night sweats, weight and appetite loss, and vaginal discharge. Her menses were normal. Seven years prior to presentation, she also had generalized lymph node tuberculosis with discharging cervical and inguinal sinuses, for which she had received a full course of anti-tubercular therapy. Her tuberculosis was completely cured by the anti-tubercular therapy and she did not show any evidence of a recurrence. Her general physical examination was normal and there was no lower limb edema. She had a 15 x 7 cm labial swelling on the left side and a 9 x 5 cm labial swelling on the right side (Figure 6). The skin overlying the swellings was thickened. She had the puckered scars of healed sinuses without any palpable lymph node in the inguinal and cervical regions (Figures 7 and 8). The rest of the physical examination, including her vaginal wall, chest and abdomen, was normal. All of our routine investigations, including hemoglobin, total and differential cell counts, blood urea nitrogen, Mantoux test, night blood smear, chest X-ray, ultrasound of her abdomen and pelvis, and pap smear were normal. She was taken up for surgery and a wide local excision with primary closure was performed. Both of her labia majora were given a natural soft and bulging appearance. There was slight oozing in the post-operative period, but healing occurred with primary intention (i.e.the incisions that were closed with sutures healed normally). Her post-operative period was uneventful. A follow-up period of six years revealed a satisfactory recovery and, unlike case report 1, she experienced minimal discharge from the wound site and her recovery was uneventful. A histopathological examination of the specimen in both cases showed changes of lymphedema. The features were suggestive of non-specific inflammation. There was, however, no clear evidence of tuberculosis in the specimens (in the form of granulomas and/or acid fast bacilli), malignancy, filariasis or donovanosis(Figure 5).

PMC4532012_01

Female

A 67-year-old Korean female was admitted to our hospital because of intermittent fever for 2 months. Four years before admission, she had visited a hospital because of fever and abdominal pain, and cholecystectomy was done due to acute calculous cholecystitis. The fever was persistent and she had taken oriental herb medicine, thereafter, she had been in excellent health until 2 months earlier, when diabetes mellitus developed which was treated by oral hypoglycemic agent. In spite of enthusiastic management in the private clinic, fever developed again and was persistent. The patient was a housewife, non-smoker and did not drink at all. There was no history of pulmonary tuberculosis. She complained of general weakness, fatigue, fever, weight loss (2.5 kilograms over 2 months) but denied cough, dyspnea, abdominal pain, nausea, vomiting, hemoptysis, frequent voiding and bladder or bowei dysfunction. The body temperature was 37.5 C, the pulse rate was 100/min, the respiration rate was 18/min and the blood pressure was 110/60 mmHg. On physical examination, she was pale and chronically ill-looking with alert mental state. She had pale conjunctiva and dehydrated tongue, and lymph nodes were impalpable. The lung, heart and abdomen were normal except for post-operative abdominal scar on the right upper quadrant. The hemoglobin was 10.5 g/dl and the hematocrit 31.4%. The white cell count was 6,700/mm3, with 77.9% neutrophils, 0.9% lymphocyte, 6.9% monocytes and 2.3% eosinophils. The platelet count was 206,000/mm3. The erythrocyte sedimentation rate was 49 mm/hr. The aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were 13.6 and 9.0 IU/L, the alkaline phosphatase 71.2 IU/L, the total protein and albumin 6.1 and 3.3 g/dl, the direct bilirubin 0.2 mg/dl, the blood urea nitrogen and creatinine 5.9 and 0.5 mg/dl, the total cholesterol 134.1 mg/dl and total calcium was 7.6 mg/dl. The urine was normal. The alphafeto protein was below 5 ng/ml and the carcinoembryonic antigen was 1.44 ng/ml. The thyroid function test was normal. The angiotensin converting enzyme was 23.1 U/ml (normal: 8-52U/ml). The brucella antibody was negative. The anti-mitochondrial antibody was negative. The sputum smear and culture for mycobacteria and fungus were negative. The chest X-ray showed a fibrosteak density in the right upper lobe and increased interstitial marking in both lungs. This finding was suggestive of inactive pulmonary tuberculosis (Fig. 1). The abdominal CT (computerized tomography) showed mildly dilated both intrahepatic ducts without internal calcific density and the common bile duct was not dilated (Fig. 2). The bone marrow biopsy showed normocelluarity (about 30% cellularity) with polymorphous cellular population and adequate megakaryocytes. The culture of bone marrow grew neither bacterium nor fungus. The needle biopsy of the liver showed relatively intact lobular architecture and hepatic cord arrangement and the portal area was some-what widened by infiltrated inflammatory cells and fibrosis, but the limiting plate was intact. There were a focal hepatocytic necrosis, perivenular cholestasis and a few ill-defined aggregates of epitheloid cells. No acid-fast bacillus was found (Fig. 3). The antituberculosis medication was prescribed for 2 weeks as a therapeutic trial. Even after that, the temperature was 38.7 C. Thereafter, we prescribed prednisolone 1 mg/kg under the diagnosis of idiopathic granulomatous hepatitis.

PMC4154285_01

Male

The patient is a 29 year old sandblaster from Tehran with history of acute silicosis, pulmonary tuberculosis and secondary alveolar proteinosis on anti TB medications for a month and lung transplant candidate who presents with acute respiratory distress to our hospital. His respiratory symptoms have worsened in 10 days and in the past two days later was bed-bound. He denied fevers, chills or night sweats but produced small amounts of sputum. He also denied hemoptysis, and lost weight of 8 Kg in the two months with decreased appetite in few days. Two months prior to this admission, he was hospitalized in the TB ward with complaint of weakness, shortness of breath, cough and fever and chills. He also complained of headaches. He denied contact with a tuberculosis patient or any other medical conditions. Sputum smear was once positive for Acid Fast bacilli. He had undergone bronchoscopy and transbronchial biopsy and was diagnosed with silicosis and secondary alveolar proteinosis with an inflammatory necrotic lesion consistent with tuberculosis. Bronchoalveolar fluid lavage smear and biopsy showed numerous dust laden macrophages, squamous and columnar epithelial cells and was negative for malignancy. At this time, he was diagnosed with acutely exacerbated silicosis and secondary alveolar proteinosis. After evaluation, he was placed in lung transplant list. He received anti TB medications and intravenous hydrocortisone. At presentation, his medications were isoniazid, ethambutol, rifampin, pyrazinamide and prednisolone. He was prevented from medication allergies. He was married, worked as a sandblaster and denied smoking or substance abuse. He did not have family history of any diseases. On physical examination, the patient was in respiratory distress. Blood oxygen saturation on arrival was 55-60% and oxygenation with a reserve bag mask eventually improved oxygen measurement upto 90 to 95%. The patient had a temperature of 38.3 oC, pulse rate 160, respiratory rate 22 and blood pressure 120/80. He was cyanotic due to respiratory distress. No lymphadenopathy was found. Cardiac exam showed present heart sounds S1 and S2 with no murmurs. Rales in both lungs were found. Abdominal exam was soft, nontender with no organomegally. Clubbing and edema was not present. Cardiac, neurologic and abdominal exam were all normal. High resolution computed tomography (HRCT) of the lungs showed bilateral alveolar ground glass opacities and consolidations prominently in mid upper zones with inter lobular septal thickening. The patterns were noted to be characteristic but not diagnostic for pulmonary alveolar proteinosis with silicoproteinosis. In comparison with previous CT scan (two months prior) disease progression was noted (Fig. 1). Laboratory values are shown in Table 1 and the report for radiology and pathology shown at the end of the report. Sputum cultures, from previous hospitalization was negative for mycobacteria, BAL smear and polymerase chain reaction (PCR). He had negative TB cultures from this hospitalization as well. The patient had spiked fevers up to 38.5oC and sweats during his hospital stay. Multiple arterial blood gases (ABG's) showed hypoxemia so oxygenation with reserve bag mask was administered. He was continued with TB medications and started on broad spectrum antibiotics clindamycin, Ceftazidime. Parenteral hydrocortisone was administered for diagnosis of acute silicosis. Furthermore, the aggressive nature of the disease caused concern about pneumocystis carinii (PCP) and cotrimoxazole was administered. Medications were continued during hospital stay of 16 days. Sputum for bacteriology was collected and bronchoalveolar lavage done with BAL. Bronchoalveolar lavage (BAL) microscopic study showed many dust laden alveolar macrophages and was negative for malignancy and diagnosis of accelerated (cellular) phase of silicosis associated with secondary alveolar proteinosis was made. Upon negative sputum and BAL smear and cultures on discharge and according to previous positive pathology, the overriding diagnosis of tuberculosis was settled and medications switched to TB coverage. He was a candidate for therapeutic lung lavage but too ill to undergo it. He was discharged from hospital with an oxygen mask, TB medications and prednisolone 40mg/day. Resistant tuberculosis and acute silicosis was in the differential diagnosis for this patient with sudden progression of disease. Shortly in a few days, the patient returned to the hospital emergency department with respiratory failure and hypoxemia. SPO2 on arrival was 55-60% with reserve bag mask. In attempt to intubate the patient, he suffered from cardiopulmonary arrest and died despite continued effort.

drug-resistant, pulmonary alveolar proteinosis, silicosis, silicotuberculosis, tuberculosis

PMC8244180_01

Female

The patient was a previously healthy 49-year-old Caucasian female who presented to the hospital with abdominal pain associated with nausea, vomiting, and weight loss. CT of her abdomen showed circumferential wall thickening of the ascending colon, highly suspicious for colonic carcinoma with associated pericolic and upper abdominal lymphadenopathy and splenomegaly with several splenic hypodensities suggestive of metastases was also noted. The patient underwent laparotomy with hemicolectomy, histopathology revealed ascending colon adenocarcinoma. Five lymph nodes were positive for metastatic carcinoma and multiple sarcoidal noncaseating granulomas were also noted. PET (positron emission tomography) scan following surgery revealed mediastinal bilateral hilar lymphadenopathy and splenomegaly with marked abnormally increased metabolic activity suspicious for metastasis. Prior to her presentation, there was no chest imaging available for comparison. Splenic biopsy showed multiple granulomas with focal necrosis. Stain was negative for fungal and acid-fast microorganisms. Blood work at the time showed Ca of 9.1 mg/dl, Cr of 0.9 mg/dl, CEA level of 9.6 ng/ml, and ACE level of 45 nmol/ml/min. CRP and ESR were not checked as they could be falsely elevated in postoperative state. Given the absence of respiratory symptoms and minimally elevated serum ACE level, no treatment was deemed necessary for asymptomatic incidental sarcoidosis and the patient was started on chemotherapy to treat cancer. Two years later, a follow-up PET scan revealed increased lymphadenopathy in multiple areas including the left axilla and the left mammographic chain and mesenteric lymphadenopathy. Lesions were also noted in the liver and spinous processes of L3-L4. Progression of her splenic involvement was also noted (see Figures 1 and 2 ). Liver biopsy at the time showed only noncaseating granulomas with no evidence of malignancy (see Figure 3). At that time, her CEA level had increased from 3 to 14.2 ng/ml and ACE level was >120 nmol/ml/min, ESR was>100 mm/hr, CRP was 15.5 mg/L, and Cr was 1.7 mg/dl. QuantiFERON-TB Gold and ANCA antibodies were all negative. Given the presence of biopsy-proven sarcoidosis with elevated ACE level, compatible imaging, and the fact that serum CEA can also be elevated sarcoidosis, the patient was started on 40 mg of prednisone for treatment of sarcoidosis flare. Following two months of therapy, blood work showed significant improvement. Serum ACE level was down to normal at 35 nmol/ml/min, Cr improved to 1.01 mg/dl, and CRP decreased to 12.4 mg/L; however, CEA increased to 98 ng/ml. Repeated PET scan showed resolution of the hilar lymphadenopathy with improvement of the left axillary and liver metabolic activity. Previously reported increased splenic and bone metabolic activity had also resolved (see Figures 4 and 5). Mesenteric lymphadenopathy, however, had progressed. Biopsy of the mesenteric lymph node showed recurrence of cancer. The patient was referred to oncology to continue treatment for colon cancer, and, finally, hospice was offered given the poor response.

PMC7396123_01

Female

A 22-year-old Gravida II, abortion I came to our institution on referral from a primary hospital with a referral paper and sonography showing that she had IUFD. She had a spontaneous abortion for which dilation and curettage (D&C) was performed at the primary hospital 16 months back. She had no remarkable medical and surgical histories. She had regular antenatal care follow-up at the primary hospital and had 8 months of amenorrhea. Upon admission, the patient was clinically asymptomatic and stable, showing no uterine contractions and no cervical dilatation. On abdominal examination, the uterus was enlarged equivalent in size to 30 weeks of pregnancy. On examination, her BP was 120/75 mm of Hg, pulse 85/minute, temperature 36.5 C, and respiratory rate 22/minute. FHS was absent Obstetric ultrasonography revealed a singleton, intrauterine fetal demise with a gestational age of 32 weeks, estimated fetal weight of 1.3 kg, and negative fetal heartbeat. The placenta was fundal and anteriorly. The cervix was closed, uneffaced, and posterior. All laboratory investigations were normal. Initially, she was administered 50 mcg of vaginal misoprostol at 6-hour intervals, without response after the 6th dose. Then, she was given an infusion of normal saline 0.9% with 5 IU of oxytocin, followed by increasing concentrations of the same infusion. Just then, there was no cervical dilation, despite the onset of contractions. Cervical effacement with no dilatation was seen. Finally, a Foley catheter was used. All attempts were unsuccessful. The patient was counselled and underwent a cesarean section horizontally under spinal anaesthesia. The intraoperative finding was intact rudimentary horn pregnancy. Clamps were applied over the fibrous band on the medial side and the fallopian tube and ovarian and round ligaments on the lateral side; the accessory horn was excised with the dead fetus; and right salpingo-oophorectomy was performed (Figures 1 and 2). On releasing the forceps applied to the fibrous band and probing, a canal was detected between the rudimentary horn and the uterine cavity at the level of the isthmus. The round ligament, ovarian ligament, and tube were connected to the right cornua of the uterus. The patient was advised to follow up. The patient had uneventful postoperative recovery and was discharged after 3 postoperative days.

PMC6243327_01

Female

The most common extraintestinal manifestations of Crohn's disease involve the eyes, skin, and the hepatobiliary, musculoskeletal and respiratory systems. These include conditions such as uveitis, episcleritis, erythema nodosum, pyoderma gangrenosum, sclerosing cholangitis, sacroilitis and organizing pneumonia. Mass-forming granulomatous inflammation in extraintestinal organs is extremely rare, with only a few recent reports of patients with Crohn's disease presenting with inflammatory pseudotumours in the liver, pancreas and kidneys. We present a case of mass-forming renal granulomatous inflammation in a patient with Crohn's disease. A 31-year-old female was diagnosed with Crohn's disease based on characteristic clinical features, and colonoscopy and histology of small and large bowel demonstrating non-caseating granulomas. She had undergone an ileocolic resection in 2009, following which she was treated with azathioprine and intermittent prednisolone. MRI was performed in February 2012 for investigation of a 2-week history of abdominal pain and diarrhoea, demonstrating active enterocolitis and also revealing an incidental left renal mass that was a new finding since a CT scan of the abdomen performed in October 2011. The focal mass was located in the inferior pole of the left kidney and measured 2.5 x 2.9 x 2.3 cm; it had a lobulated margin and homogeneous signal, being slightly hypointense to the renal cortex on both T2 half-Fourier acquisition single-shot turbo spin-echo and true fast imaging with steady-state free precession images (Figure 1). The mass was isointense on pre-contrast T1 volumetric interpolated breath-hold examination and following contrast showed a honeycomb-type appearance with irregular enhancing septa around small non-enhancing elements that measured between 1 and 5 mm (Figure 1). The lesion had restricted diffusion and there was no abnormality within the perinephric fat or renal vessels (Figure 1). As the renal mass was an incidental finding on MRI focused on the small bowel, a dedicated contrast-enhanced renal CT scan was performed. On CT scan, the mass was isodense pre-contrast and homogeneously hypoenhancing in the arterial phase, while in the portal venous and delayed phases, it was hypoenhancing with cystic type non-enhancing foci within. No calcification or adenopathy was seen (Figure 2). Sonographically, the mass was slightly hypoechoic and had no demonstrable vascularity (Figure 3). The differential diagnosis was focal pyelonephritis, including bacterial and mycobacterial aetiologies, renal neoplasm and inflammatory pseudotumour. A QuantiFERON Gold assay (an interferon-gamma release assay used as a diagnostic test for latent tuberculosis infection) was performed and a negative result was obtained. The patient had no prior history of tuberculosis or known tuberculosis contact, and multiple early morning urine cultures were negative. She received a short course of empiric intravenous antibiotics followed by oral amoxicillin/clavulanic acid. However, these were stopped, as the patient was clinically well. The lesion was stable on follow-up ultrasound imaging in May 2012 and this prompted an ultrasound-guided biopsy, providing histology that demonstrated a dense, mixed chronic inflammatory infiltrate with foci of granulomatous inflammation with focal necrosis. Some palisaded histiocytes with areas of necrosis were seen but there were no giant cells or polarizable foreign material present. Special stains for organisms, including periodic acid-Schiff and Ziehl-Neelsen, were negative and there were no features of malignancy (Figure 4). Mycobacterium tuberculosis polymerase chain reaction on tissue biopsy was negative. A tentative diagnosis of an inflammatory pseudotumour was made and a course of 30 mg daily of prednisolone was commenced, resulting in resolution of the lesion, with only a small focus of scar present on follow-up ultrasound and CT imaging performed in October 2012 (Figure 5). This response confirmed the diagnosis of inflammatory pseudotumour associated with Crohn's disease.

PMC5498209_01

Female

A previously healthy 57-year-old woman visited a local hospital for a cough and nasal discharge persisting for 3 months. Blood tests revealed severe leukopenia (700/muL), and a computed tomography (CT) scan revealed pneumonia in the right lung and mild-to-moderate splenomegaly (Fig. 1a and b). She was therefore suspected of having a hematological disorder and was referred to our hospital. Upon the initial visit to our hospital, she was afebrile, and her vital signs were unremarkable. No skin lesions were observed. She had a history of pregnancy, and she had no family history of hematological or autoimmune diseases. She had taken no medication for at least three months. Her white blood cell count was 710/muL (neutrophils: 11%; lymphocytes: 57%), red blood cell count was 4.23x106/muL, hemoglobin was 12.2 g/dL, hematocrit was 36.3%, mean corpuscular volume was 85.8 fL, reticulocyte count was 85x103/muL, and platelet count was 141x103/muL. Her findings for serum biochemical tests were all normal (Supplementary Table 1). C-reactive protein was weakly positive (0.5 mg/dL), and soluble interleukin-2 receptor (sIL-2R) was elevated (1,880 U/mL). Serological tests excluded infection with hepatitis B and C viruses, HIV, Mycoplasma pneumoniae, Chlamydia pneumoniae, and Mycobacterium tuberculosis, and tests for Epstein-Barr virus indicated a previous but not recent infection (supplementary Table 1). Fluorodeoxyglucose (FDG) positron emission tomography-CT revealed diffuse and mild FDG uptake in the spleen and the bone marrow of the trunk and proximal extremities. A bone marrow biopsy revealed a slightly hypercellular marrow with mild reticulin fibrosis (Fig. 2a). Bone marrow smears revealed a decrease in mature segmented neutrophils (0.4%) with a relative increase in myelocytes without an increase in blastic cells (Fig. 2b, Supplementary Table 2). Phenotypically abnormal lymphoid populations were not detected by flow cytometry. Morphological dysplasia was not detected in any of the hematological cell lineages. The myeloid:erythroid ratio was 2.27. Flow cytometric analyses detected no abnormal cell populations in the bone marrow cells, and a chromosomal analysis showed a normal karyotype. To screen for autoimmune diseases, a series of autoantibodies were measured. The results indicated that anti-single stranded DNA antibody was positive (209 AU/mL), rheumatoid factor was weakly positive (11.7 IU/mL), and antinuclear antibody was weakly positive, with a titer of 1:40. Other autoantibodies, including anti-double stranded DNA, anti-ribonucleoprotein (RNP), and anti-SS/A antibodies were negative. The indirect granulocyte immunofluorescence test (GIFT) detected antibodies that reacted with both human neutrophil antigen (HNA)-1a and HNA-1b in her serum (Table 1). HNA typing by the GIFT revealed that the patient had HNA-1a/1b alleles, indicating that the antibodies detected in her serum were autoantibodies. Because her symptoms and signs did not meet the diagnostic criteria for common autoimmune disorders, such as rheumatoid arthritis, Sjogren's syndrome, or systemic lupus erythematosus, the patient was diagnosed with primary AIN. Oral levofloxacin and itraconazole were administered for pneumonia, and, because spontaneous recovery of her neutrophil count was expected, she was followed as an outpatient. However, 5 weeks later, severe neutropenia persisted, and we admitted the patient to our hospital and began daily subcutaneous injections of G-CSF at a dose of 5 mug/kg. She developed a high-grade fever on the day of admission, and oral levofloxacin was switched to intravenous tazobactam/piperacillin. Her body temperature normalized on post-admission day 3. However, her neutrophil count, which was 130/muL on admission, did not respond to G-CSF therapy through day 8, so we discontinued G-CSF therapy and started oral prednisolone at a dose of 0.5 mg/kg/day (Fig. 3). Her neutrophil count began to increase immediately (Fig. 3). Chest X-ray taken 15 days after the initiation of prednisone showed that the pneumonia had improved. Twenty-eight days after starting prednisolone, autoantibodies against HNA-1a and HNA-1b had disappeared from her serum (Table 1). Abdominal CT revealed improvement in her splenomegaly (Fig. 1c), and she was discharged four days later. The prednisolone dosage was gradually tapered and was discontinued 10 months after its initiation (Fig. 3). Her neutrophil count remained normal at her last visit (two months after discontinuation of prednisolone).

autoimmune neutropenia, granulocyte-colony-stimulating factor, human neutrophil antigen

Computed tomography (CT) scans. CT scans taken during the initial visit to a local hospital showed mild pneumonia in the right upper lobe.

PMC6472884_01

Female

Patient 1 is a girl who received BCG vaccine when she was 4 months old, then a lump of finger size began to appear under her left armpit. When they came to the Wuhan jinyintan hospital, the lump had appeared for nearly four months. Blood routine examination displayed the number of leukocytes were increased. The patient was given debridement and treatment with anti-inflammatory drug of cephalosporins as well as isoniazid (INH). Patient 2 is a girl who received BCG vaccine when she was 3 months old. After one month, her parents found a lump about 3.0x 2.0cm in her left armpit. The patient was treated with anti-infection and external application of Chinese Medicine. Patient 3 is a boy, who received BCG vaccine, a big lump in the left armpit were found by his parents when he was 8 months old. The lump's size like a pigeon egg. Puncture showed tuberculosis in lymph nodes and acid-fast stain is positive in these three patients, the three patients also received other test and were diagnosed with Mendelian susceptibility to mycobacterial disease (MSMD) in Wuhan Jingyintan hospital. Pedigree of the three families were shown in Fig 1.

PMC6699147_01

Male

A 39-year-old man was admitted to our hospital on December 23, 2015, with back pain, numbness and weakness of lower limbs for 2 months. Thoracic disc herniation was considered in local hospital 2 months ago; however, conservative treatment did not work. Moreover, the disease quickly progressed to paraplegia on December 24, 2015. The neurologic examination demonstrated a minor motor impairment of lower limbs and reflexes were hyperactive. Anal sphincter tone was without damage, negative Hoffman, Tromner and Babinski's sign. He presented a sensory level of hypoesthesia and loss of thermalgesia at T7. T-SPOT.TB was positive. The enhanced magnetic resonance imaging (MRI) of thoracic vertebra on December 24, 2015 (Figure 1), suggested that thoracic 7 vertebral body, the thoracic 7 and 8 vertebral body accessory tuberculosis was considered, accompanied by intraspinal abscess formation. He was misdiagnosed with thoracic tuberculosis. Posterior pedicle screw fixation + spinal canal decompression + lesion clearance + bone grafting and fusion was performed on December 25, 2015. Surgical pathology suggested DLBCL. The immunohistochemical (Figure 2) hinted tumor cells CD20 (+), CD79a (+), PAX-5 (+), Bob-1 (+), Oct2 (+), CD10 (+), BcL-2 (+), Bcl-6 (+), CD15 (-), CD30 (+), CD23 (+), CD21 (+), MUM1 (+) and Ki-67 (+ >30%). Reactive cells CD3 (+), CD5 (+), CD43 (+), CD45RO (+); CDla (-), ALK (-), EMA (-), TdT (-), CD117 (-), HMB45 (-), S100 (-), CD31 (-), CK (-) and EBER (-). 18F-fluorodeoxyglucose (18F-FDG)-positron emission tomography/computed tomography (PET/CT) imaging on January 14, 2016 (Figure 3A and B) showed T8-10 vertebral body, retroperitoneal enlarged lymph nodes, left iliac bone and left femur with increased uptake of 18F-FDG. Based on these, systemic chemotherapy with rituximab + CHOPE (R-CHOPE) was determined as an appropriate treatment for the patient since January 20, 2016. After four cycles of chemotherapy with R-CHOPE, PET/CT on May 12, 2016 (Figure 3C and D) suggested that, compared with PET/CT on January 14, 2016, 18F-FDG uptake concentration in the original area all disappeared, suggesting that the tumor was relieved. Then, the strength of both lower extremities gradually recovered, and he could walk. After another two cycles of chemotherapy with R-ECHOP on May 14, 2016, and on June 11, 2016, respectively, the patient went to follow-up time. During the nearly 2-year follow-up, the disease still has no relapse. Ethical approval was not necessary for the case report. The patient has consented for the publication of the present case report.

diffuse large b-cell lymphoma, epidural

PMC3649607_01

Male

A 75-year-old patient presented with complaint of hematuria. Ultrasonography revealed a solid 2-cm mass on right wall of the bladder. Cystoscopy confirmed bladder tumor and patient underwent transurethral resection of bladder tumor. The pathologic diagnosis was pTa, G2 transitional cell carcinoma and carcinoma in situ (WHO 1973). He was offered six weeks of BCG instillation (OncoTICE , Tice Strain, administered intravesically after reconstitution in 50 ml saline). The patient was unable to complete the treatment cycles consecutively due to severe irritative symptoms; hence at the second and fourth week, treatment cycles were cancelled for a period of one week and his symptoms were treated with antibiotics and antispasmodics. Urine cultures were negative for bacterial colonization but pyuria was present at urine analysis. He had no gross hematuria, fever or chills. He was administered five cycles of BCG at full dose, atraumatically, by a staff urologist using a 12Fr hydrophilic Nelaton catheter. There was no external spillage during the administration of BCG. One week after the last instillation the patient reported penile swelling and tenderness, itching at suprapubic areas. Two days later, he presented with a penile lesion and indurated lesions at the suprapubic area. Physical examination demonstrated two areas of painless indurated lesions at the pubic area and shallow ulceration on the penil shaft [Figures 1a and b] and bilateral palpable inguinal lymphadenopathy. He had low-grade fever without chills. He had no history of tuberculosis, diabetes or immunodeficiency. Chest X-ray was unremarkable and computed tomography (CT) of abdomen revealed bilateral inguinal adenopathy (maximal length of diameter 1cm on the left and 1,5 on the right side). Laboratory data showed slight elevation of C-reactive protein and erythrocyte sedimentation rate, and otherwise blood chemistry was normal. Polymerase chain reaction (PCR) for urine tubercle bacilli was negative, and thereafter urine cultures were also negative for mycobacterium. The patient underwent diagnostic biopsy from the papules of pubic areas and cystoscopy at the same time. Cystoscopy showed several erythematous areas in the bladder and cold-cut biopsy was obtained from these areas. Pathology of the bladder biopsies revealed acute and chronic inflammation with granulomatous changes; there was no evidence of malignancy. The pathologic examination of biopsy samples from endurated pubic lesions demonstrated granulomatous inflammation with caseous necroses [Figure 2] and multinucleated giant cells of Langhans type, which was compatible with BCG-induced granulomatous skin infection. Intravesical BCG instillation therapy was discontinued and the patient was given a three-drug antitubercular regimen including rifampicin, isoniazid, and pyrazinamide. The total treatment course was six months, with discontinuation of pyrazinamide after two months. Complete resolution of penile, pubic lesions and inguinal adenopathy was achieved at six months of treatment [Figures 1c and d]. Follow-up cystoscopy showed no evidence of tumor recurrence and CT of abdomen and chest X-ray were unremarkable.

bacillus calmette-guerin, bladder cancer, balanitis, complication, intravesical treatment

PMC10017523_01

Female

A 49-year-old woman presented to our hospital in August 2020, complaining of post-coital bleeding with no abnormal vaginal discharging. The patient began having vaginal bleeding after sexual intercourse around 1 month before admission. She had a history of didelphic uterus with cervix duplex. The time of first discovery of her genital malformation was uncertain. And she'd been pregnant four times, with one cesarean section and three induced abortions, including one abnormal pregnancy in the left uterus that resulted in a supracervical hysterectomy around 16 years ago. Previously, she had regular menstrual cycles of 30 days with menstruations of 5-6 days. She had moderate menstruation volume and no dysmenorrhea. The patient had not previously had a routine physical examination. Her latest cervical screening was three years ago, and she underwent an appendectomy eight years ago. There was no family history of tumors or genital malformations in her family. Gynecological examination indicated a normal-appearing right cervix, the surface was smooth, but it was easy to bleed when touched, and the non-dominant side of the left cervix was concealed by the side wall of the left vagina. After exposing, the left side cervix presented a mature appearance which was smaller than a normal cervix ( Figure 1 ). Bimanual rectovaginal examination can detect the lack of uterine body, pelvic cavity emptiness, and no abnormalities in bilateral parauterine regions. Her blood carbohydrate antigen 125 (CA125), carcinoembryonic antigen (CEA), alpha fetoprotein (AFP), and carbohydrate antigen 153 (CA153) levels were all within normal ranges (CA125 17.2 U/ml, CEA < 0.5 ng/ml, AFP 1.5ng/ml, CA153 5.5 U/ml), however the carbohydrate antigen-19-9 (CA19-9) level increased considerably, the corresponding results was 112.59 U/ml. Colonoscopy and gastroscopy revealed no visible abnormalities. The cytology result of liquid-based cell testing in the right cervix was normal, whereas the left cervix revealed atypical glandular epithelial cells. Both cervical smears were negative for human papilloma virus (HPV), including high risk HPV16, 18, 31, 33, 35, 39, 45, 51, 52, 53, 56, 58, 59, 66, 68, 73, 82, and low risk HPV6, 11, 42, 43, 81, 83. Histopathology of the two cervices from colposcopy-directed punch biopsy (CDB) and endocervical curettage (ECC) revealed: 1. (RIGHT CDB) adenocarcinoma at 3,6,12 o'clock on the right cervix, IHC: ER (focal weak+), CK7 (+), CDX2 (-), Muc-6 (-), P53 (+, positive rate of 20%), Ki67 (approximately 30%); 2. (RIGHT ECC) the submitted tissue is a small blood clot; 3. (LEFT ECC) the submitted tissue is a little mucus; 4. (LEFT CDB) chronic inflammation at the left cervix. Pelvic magnetic resonance imaging (MRI) revealed two cervical canals and a 1.9cmx1.6cm mass inside the left cervix ( Figure 2 ). The left wall of the right cervix may be involved by the tumor in the left cervix. A few small lymph nodes on both sides of the pelvic could be seen. And there was no lymphovascular space invasion or enlarged pelvic lymph node identified. In addition, there was only one right kidney, with no left kidney. The biopsy of the patient's right cervix indicated adenocarcinoma, while MRI revealed that the tumor was situated in the left cervical canal and had invaded the neighboring right cervix. After much deliberation, the diagnosis of adenocarcinoma of the left cervix stage [IB1, International Federation of Gynecology and Obstetrics (FIGO), ] and stage T1b1N0M0 [American Joint Committee on Cancer (AJCC), ] was made. In the first step, we performed cystoscopy, the right ureteral D-J tube implantation, and pelvic sentinel lymph node biopsy under laparoscope. The hyperstaging of pathology revealed that three sentinel lymph nodes had no cancer metastases. Then, we conducted radical cervical resection with bilateral salpingo-oophorectomy, and bilateral pelvic lymphadenectomy without the use of a manipulator. The intraoperative diagnosis was consistent with the preoperative diagnosis. The double cervices were dissected after surgery. After the resection, the morphology of the double cervices was seen to be irregular. Tumors were seen between the duplex cervices' circumferential walls. The tumor was around 2cmx2cmx2cm in the left cervix and penetrated the neighboring right cervical tissue without infiltrating the vagina or the parametrium. Microscopically, the morphology and immunohistochemistry of the duplicated cervices revealed gastric-type adenocarcinoma with high and intermediate differentiation, as well as intestinal differentiation in some regions. The tumor grew endogenously, penetrating the whole layer of the left cervical wall as well as the shallow layer of the right cervical wall (about 1/3 of the cervical wall). There was lymphatic vascular space infiltration (LVSI), but no clear nerve invasion or malignancy in the bilateral parauterine, vaginal stump, or vaginal vault. Pathological examination revealed no tumor involvement in the lymph nodes. There was no evidence of malignancy in the ovarian and fallopian tube tissues on either side. Additionally, no cancer metastases was discovered in the lymph nodes that were removed (0/18). Immunohistochemistry of the tumor cells were as follows: Muc-6 (+, focally), P16 (+, focally), P53 (20% medium intensity +), ER (+, focally), PR (-), CK7 (+++), CK20 (+, focally), Muc-2 (+, focally), Muc-5 (++), CDX-2 (+), SATB2 (-), Pax-8 (-), and the ki67 proliferative index was around 15% ( Figure 3 ). All 23 HPV subtypes tested negative, including high-risk HPV16, 18, 31, 33, 35, 39, 45, 51, 52, 53, 56, 58, 59, 66, 68, 73, 82, and low-risk HPV6, 11, 42, 43, 81, 83. Following surgery, she had concomitant chemoradiation, a total dosage of 60 Gy pelvic irradiation, and three cycles of chemotherapy comprising paclitaxel and carboplatin. Currently, 29 months after the final treatment, the patient has normal cytology and colposcopy results with negative HPV tests.

cervical stump carcinoma, didelphic uterus, duplicated cervices, endocervical adenocarcinoma, gastric-type, human papilloma virus

PMC5753896_01

Female

The patient is a 69-year-old female with the past medical history of hypertension, hyperlipidemia, hypothyroidism, and with interstitial cystitis. A written informed consent for publication of this case has been obtained. She reported GERD symptoms for the past 16 years. Her GERD symptoms included heartburn, oral acid taste, regurgitation and epigastric discomfort. Medical treatment using proton pump inhibitors (PPI) only provided partial relief of these symptoms. The patient became PPI dependent and was unwilling to stop PPI even for a wireless pH study. She also had undergone four esophagogastroduodenoscopies (EGDs) for diagnostic purposes only and was not offered any intervention apart from recommending a different PPI. She increased frequency of PPI use to twice daily. The patient was referred for evaluation for transoral incisionless fundoplication (TIF). Her examination was remarkable for the scars from her previous surgeries (laparoscopic cholecystectomy and hysterectomy). Her body mass index was 33.9. She completed the GERD-related quality of life questionnaires. The score of the GERD health-related quality of life (GERD-HRQL) questionnaire was 20. Reflux symptoms index (RSI) questionnaire score was 11. GERD symptom score (GERSS) questionnaire score was 5. Her preoperative evaluation consisted of barium esophagram which showed good esophageal motility and a small hiatal hernia. EGD showed 2 cm sliding hiatal hernia with Hill deformity of II. Patient had abnormal gastroesophageal junction with Los Angeles class A esophagitis. Patient declined to stop PPI for esophageal pH testing due to severe GERD symptoms. We performed 48 h wireless pH probe study yielding a DeMeester score of 1.7. Preoperative esophageal manometry showed normal peristalsis and normal lower esophageal sphincter pressure and relaxation. We discussed the option of laparoscopic Nissen fundoplication; however, the patient was interested only in natural orifice anti-reflux procedures. She was found to be a good candidate for TIF. She was the second patient to undergo this procedure by a TIF certified experienced endoscopic surgeon. Informed consent was obtained after we discussed the nature of the procedure and the surgeon's experience. The patient clearly indicated that she did not want to receive blood or blood products regardless of medical consequences. She underwent the standardized TIF procedure using EsophyX HD device (EndoGastric Solutions, Redmond, WA, United States). The endoscopic retroflexed views of the native gastroesophageal valve (GEV) and the reconstructed GEV after TIF are illustrated in Figure 1. We performed an approximately 270 fundoplication with a GEV length of 3 cm. Her postoperative course was unremarkable and she was discharged the following day. There were no complications, presentations to the emergency department, or return to the operating room. The patient was successfully weaned off PPI within 2 weeks following TIF. She completed the same GERD-related questionnaires at 5 and 24 months following the TIF. The improvements are illustrated in Table 1.

jehovah’s witness, transoral incisionless fundoplication, gastroesophageal reflux disease, minimal invasive surgery

PMC7607930_01

Male

A 16-year-old male patient applied to our emergency service with right ankle pain following a football injury. His history revealed forced acute hyperplantar flexion. There was a mild swelling at the posterolateral side of right ankle and he had difficulty in walking. Posterior ankle and back of the lateral malleoli were painful by palpation. Os trigonum fracture was detected at lateral X-ray of the right ankle (Figure 1). Fracture was seen more clearly when actual X-rays were compared to the patient's older X-rays which were taken when he presented to our clinic because of ankle sprain two months ago (Figure 2). The patient had been treated with a short leg splint, since no fracture was detected. The splint was removed one week later and joint range of motion and strengthening exercises were started. After three weeks, the patient was fully recovered. A written informed consent was obtained from the legal guardian of the patient. Os trigonum fracture and surrounding edema were detected by CT and MRI (Figure 3). There was no additional injury. Patient was treated conservatively. A non-weight bearing short leg cast was applied. Union of fracture was seen on sixth week X-ray (Figure 4). Cast was removed after six weeks. Joint range of motion and strengthening exercises were started. The patient was allowed full weight bearing when the cast was removed. Painless and full range of motion was obtained four weeks after cast removal. The patient was followed-up for a total of three months. Nonunion, chronic pain or posterior ankle impingement syndrome was not detected in the patient after the treatment. The patient returned to sports activities without any complaints.

PMC6348731_02

Female

The patient was a 64-year-old female with a past medical history significant for pulmonary tuberculosis, and chronic hepatitis C. Thoracic radiation therapy (total dose of 60 Gy with parallel opposed-field irradiation) was performed for lung adenocarcinoma of the right middle lobe. Fever and a cough developed 6 months after the conclusion of radiotherapy and she was hospitalized in our department because of shadowing on chest computed tomography (CT). On admission, her vital signs were normal, and fine crackles were heard at the right lower lobe. Chest CT revealed consolidation outside the radiation field in the middle and lower lobes (Fig. 2A). Despite the administration of antimicrobial agents, her symptoms did not improve, and a bronchoscopy was performed. The findings from transbronchial lung biopsy were consistent with organizing pneumonia, although etiology was uncertain following blood testing, smear culture testing, and cytodiagnosis of the bronchoalveolar lavage fluid (BALF), we diagnosed her with organizing pneumonia induced by radiation therapy. She was not hypoxemic and, given her history of hepatitis C and tuberculosis, we opted to not use steroids in favor of observation only plus antitussive agents. The shadow continued to move, eventually crossing over to the other side, and completely disappeared in 5 months (Fig. 2B and C).

PMC9381353_01

Male

A 69-year-old man had been diagnosed with atrial fibrillation and cardiogenic cerebral infarction 1 month earlier and been prescribed anticoagulants. He did not show any consequences of the cerebral infarction. He was aware of his dyspnea on exertion and had a dry cough one week before admission. He had bilateral carpal tunnel syndrome for which surgery had been performed 10 years ago. No significant contributory family history was noted. He had a smoking history of 80 pack-years. His vital signs were as follows: body temperature, 36.9C; blood pressure, 139/91 mmHg; heart rate (HR), 107/min; respiratory rate, 16/min, and oxygen saturation, 96% (room air). Inspiratory crackles were audible in the lungs bilaterally. His blood test results revealed leukocytes, 8,100/muL (neutrophils, 68.3%; lymphocytes, 20.4%; and eosinophils, 2.6%), C-reactive protein, 1.08 mg/dL; KL-6, 979 U/mL, and brain natriuretic peptide, 233 pg/mL. M protein, and Bence Jones protein were not detected by immunoelectrophoresis (Table). Chest radiography revealed cardiomegaly and an infiltration shadow in the right lung field (Fig. 1A). Chest computed tomography (CT) revealed multiple infiltrative and ground-glass opacities in the lungs bilaterally (Fig. 1B). An electrocardiogram (Fig. 2A) revealed HR of 118/min, atrial fibrillation, low potentials on limb induction, and poor-R wave progression on V1-3 wave. Echocardiography (Fig. 2B, C) revealed a hypertrophic myocardium with high echogenicity. Bronchoscopy was performed to identify the cause of the clinical and infiltrative shadows. The TBLB specimen of the lower lobes of the right lung showed polypoidal organizing lesions protruding into the alveolar spaces (Fig. 3A); organizing pneumonia (OP) was diagnosed and treatment with steroids was initiated. However, cardiac amyloidosis was also suspected owing to the presence of a hypertrophic myocardium with low potentials on electrocardiographic limb guidance and a medical history of bilateral carpal tunnel syndrome. A biopsy of the stomach, duodenum, and skin was performed; however, amyloid deposition was not observed. Therefore, Congo red stain was added to the TBLB specimens, which were stained positive (Fig. 3B, C), and polarized light microscopy revealed apple green birefringence amyloid deposits (Fig. 3D) and diffuse amyloid deposits in the alveolar septum (Fig. 3B). Technetium 99m pyrophosphate scintigraphy revealed the strong accumulation of technetium pyrophosphate in the inferior wall (Fig. 4); amyloid deposition of TTR was positive and mutations with amino acid changes were not observed in the TTR gene. Based on the above findings, ATTRwt amyloidosis was diagnosed by TBLB, so we planned to administer tafamidis. Chest CT following treatment using steroids for OP revealed residual ground glass opacity under the pleura (Fig. 5), and pathology of the biopsied TBLB specimens revealed amyloid deposition in the alveolar septum; thus, we construed a diagnosis of diffuse alveolar-septal amyloidosis.

cardiomyopathy, transthyretin, wild-type transthyretin amyloidosis

PMC6701415_01

Male

A 40-year-old male patient, a lawyer from Mexico City, with no relevant chronic-degenerative background, presented with dry cough and moderate dyspnea for the last 8 months, which had gradually worsened. By this time, he had already been examined a couple of times and prescribed inhaled muscarinic bronchodilators, with partial improvement on the symptoms. Nonetheless, skin peeling on distal phalanges on both hands has emerged 15 days before his visit to the hospital, with no apparent trigger (Figure 1). Evolving over time with functional class deterioration, the patient presents paroxysmal coughing and hemoptysis; hence, his hospital admission with clinical evidence of hypoxemia and moderate anaemia (hemoglobin 8.2 gr/dl). Once hospitalized, the physical exam revealed jugular vein distention (JVD), preserved muscle strength, and subcrepitant rales in the subscapular region. Consequently, a pneumopathy research was initiated through a transthoracic echocardiogram (TTE), which showed a left ventricular concentric hypertrophy, preserved ejection fraction, and an increased pulmonary artery systolic pressure suggesting a moderate pulmonary hypertension. However, the patient persisted with respiratory deterioration, requiring invasive mechanic ventilation and further admission to the Intensive Care Unit (ICU), where he was initiated with an empirical antibiotic treatment. After 48 hours of showing a poor response to the antibiotic treatment, the staff decided to perform a high-resolution computed tomography, reporting a matching pattern of a nonspecific interstitial pneumonia (NSIP) (Figure 2). Based on these findings, a bronchoalveolar lavage was performed showing the presence of loaded hemosiderin macrophages, confirming a diffuse alveolar hemorrhage; hence, a 1000 mg pulse IV methylprednisolone and cyclophosphamide therapy was established for 3 days. A screening research for pauci-immune vasculitis was performed; nevertheless, organ damage and anti-neutrophil cytoplasmic antibodies (ANCAs) were not identified. Additionally, other causes of immune complex-mediated vasculitis were studied, but hepatitis B/C virus, tuberculosis, and HIV values were all negative and complement levels were normal. The sole finding that suggested that the patient was suffering from an autoimmune disease and was a strongly positive antinuclear antibodies ratio (1 : 1280), with cytoplasmic and ribosomal pattern, which implied to discard systemic lupus erythematosus. However, there was not enough evidence to justify a renal function deterioration, proteinuria, haematuria, or pyuria. Although the patient did not meet the classification criteria for systemic lupus erythematous, the lookup for specific antibodies for myositis was conducted, highlighting an anti-PL-12 and anti-Ro-52 strongly positive result. Accordingly, subclinical myositis was confirmed through electromyography; results showed a recruitment pattern, even when the patient had never presented muscle enzyme elevation or decreased muscle strength in a significant manner. Conclusive diagnosis included incomplete antisynthetase syndrome and alveolar hemorrhage. Once out of the intensive care unit, a prednisone 50 mg/day and methotrexate 15 mg/wk was followed for 3 months until the dyspnea and hemoptysis disappeared. Confirmed negative tests on neoplastic disease assured the patient's amelioration. One year later, the patient showed a considerable improvement of his respiratory function parameters. As a regular follow-up treatment, the patient is on low doses of methotrexate, practically asymptomatic.

PMC3700493_01

Male

A 58-year-old amateur cyclist (MTB), who was considered fit for competitive sports after a specific medical and cardiologic assessment for sports carried out in October 2011 with ECG (Figure 1) consulted a local cardiology clinic in June 2012 because of an oppressive retrosternal thoracic pain felt the day before during his participation in a competitive race. Some days earlier, he had reported a pre-flu symptomatology which had seriously weakened him. After a brief stay in a hospital cardiology department, the athlete was discharged and the diagnosis was "sub-acute inferolateral myocardial infarction in a dyslipidemic patient". Serial electrocardiographs recorded on that occasion (Figure 2) showed a high ST segment with negative T waves in the inferolateral derivations with an enzymatic increase of CPKMB and T troponin. An echocardiographic examination showed regular left ventricular volume and preserved ejection fraction in presence of ipokinesis of inferior-basal and mid- and lateral basal walls. A further coronarography (Figure 3) was basically negative, without significative endoluminal stenosis, myocardial bridge, or congenital anomalies in the context of a coronarography for right-sided heart failure predominance. The athlete was discharged and required a treatment of statins and anti-aggregants (aspirin and clopidogrel) and was advised to rest. After 2 months, a bicycle ergometer stress test was performed in the same cardiology center and the results were negative. No other etiological hypothesis was suggested, nor was any other imaging examination made, therefore the athlete was diagnosed with ischemic heart disease and was considered unfit to perform in competitive sports (prognosis "quoad vitam"). The athlete came back to us for a visit in August 2012; he asked for an accurate diagnosis for what had happened to him, wanted to understand the triggering event of his supposed myocardial infarction, and, above all, to be informed about risks related to physical activity and to his general and sports-related prognoses. A further electrocardiographic and echocardiographic check showed a clear decrease of T wave negativity in inferior leads and its disappearance in precordial antero-lateral leads, and did not find any significant wall motion or segmental kinetic anomalies, even at an infero-lateral wall level. Thus, the athlete underwent cardiac MR examinations, which, although 2 months later, showed the following: "Presence of hyperin-tense signal on T2w-STIR on the inferior medio-apical wall and the lateral-median wall of the left ventricle, mainly on the intramyocardial and epicardial side. A precocious and belated homozonal enhancement (LGR) extended to the adjacent pericardium is associated to this." In conclusion, the MR context gives initial evidence of myocarditis, with traces of activity and outcomes that are still visible (Figure 4).

cardiovascular magnetic resonance, myocardial infarction, myopericarditis

PMC3965945_01

Female

A 10-year-old Saudi girl was referred to our hospital with a complaint of progressive intermittent vomiting for 6 months. The vomiting was projectile of semidigested food content and almost always after meals. It was associated with nonspecific nonradiating epigastric pain, undocumented weight loss, progressive fatigability, and bone aches. There was no history of fever, loose bowel motions, or hematemesis. Her family history was negative for tuberculosis, peptic ulcer diseases, or gastric carcinoma. At physical examination, she was emaciated, sick, pale, and severely dehydrated. There were no palpable pathologic lymph nodes, jaundice, or skin rash. She was afebrile with pulse rate 110 beats/minute, respiratory rate 20 breaths/minute, and blood pressure 90/60 mmHg. Her weight was 18.9 kg (<5th percentile for age and sex) and height 137.5 cm (on the 50th percentile). Local examination revealed a soft and lax abdomen with fullness at epigastrium (Figure 1) with no palpable masses, organomegaly, or ascites. Another systemic examination was unremarkable. Initial laboratory investigations showed hemoglobin 14 gm/dL, white blood cell count 9.2 x 109/L, platelet count 459 x 103/mm3, erythrocyte sedimentation rate 30 mm/hr (normal, 0-10 mm/hr), and normal peripheral blood smear. Her blood gases revealed pH 7.59, PCO2 50 kPa, and HCO3 55 mmol/L. Other laboratory workup showed hyponatremia (122 mmol/L), hypokalemia (1.87 mmol/L), hypochloremia (62 mmol/L), hyperuricemia (418 mmol/L), and elevated urea (13 mmol/L) and creatinine (69 mmol/L). Her liver function test, serum amylase/lipase and lactate dehydrogenase levels were all normal. At this stage, the clinical diagnosis was gastric outlet obstruction. After correction of dehydration and electrolyte imbalance and establishment of total parenteral nutrition, she underwent barium meal which confirmed the clinical impression of gastric outlet obstruction and in addition showed a crater of an ulcer at lesser curvature (Figure 2). Ultrasound of abdomen revealed marked thickening of antral wall (12 mm in diameter) and pyloric channel (Figure 3) and moderate amount of fluid within the pelvis. Upper gastrointestinal endoscopy showed a markedly erythematous, fragile and erosive mucosa at lower esophagus, a markedly thickened antral mucosa occluding the pylorus, and a clean base ulcer 2 centimeters x 1.5 centimeters at the lesser curvature of the stomach (Figure 4). The narrowed antrum and pylorus underwent balloon dilatation; afterwards, it was possible to pass pediatric size scope (8.6 mm) through the pylorus down to the duodenum which looked normal and nasojejunal tube was passed through for continuous enteral feeding. The esophageal biopsy showed reflux esophagitis, and the antral biopsies revealed active chronic Helicobacter pylori gastritis grade IV with no metaplastic changes. The biopsies obtained from the edge of the gastric ulcer demonstrated poorly differentiated signet-ring-cell adenocarcinoma (Figure 5). For staging purposes, abdominal CT scan was performed. It revealed marked thickening of antral wall (18 mm in diameter) and pyloric channel and hypodense soft tissue densities at the celiac axis suggestive of celiac lymphadenopathy, and no definite signs of infiltration either of the liver or pancreas could be visualized. CT scan of the chest showed normal lungs, heart, and pleural spaces and no evidence of metastatic lesions or lymphadenopathy. Bone scan study was negative for evidence of metastases. The child underwent exploratory laparotomy to evaluate for resectability of the gastric tumor. There were small metastases to the liver, head of pancreas, and mesenteric lymph nodes and aspirate from ascitic fluid revealed malignant cells. Therefore, the gastric carcinoma was deemed unresectable and a gastrojejunostomy tube was placed for enteral nutrition and gastric decompression. The patient received chemotherapy consisting of cisplatin, 5-fluorouracil, and methotrexate. Followup CT scan of abdomen showed no response, so the patient was put on palliative care including analgesics. Unfortunately, she died few months after diagnosis due to advanced carcinoma.

PMC3552547_01

Male

Mr J was an 18-year-old academically gifted South American student who was visiting Italy as a tourist. He had normal neuropsychological development during infancy. He was travelling around Europe during his holidays to celebrate the end of high school. He was an easy-going person, having had many relationships but without a significant long-term partner. He had several hobbies (football, technologies, cars) and planned to start his university studies in international politics. He had not experienced any previous psychopathological problems. He did not drink alcohol or caffeine, and did not use any illicit or recreational drugs. His great-grandmother had suffered from schizophrenia. The patient was admitted to the psychiatric ward of Policlinico Umberto I Hospital, Sapienza University of Rome, appearing to be deeply distressed, dysphoric, and confused, with disorganized speech and thoughts. He presented with persecutory and transformation delusions focused on the idea that every person was a robot with a human body. He had disorganized auditory hallucinations, hearing voices of relatives (mother, father, cousins) telling him to escape from the hospital because there were robots there who wanted to kill him. He did not recognize his cousin (thinking that the cousin was a robot with the body and face of his cousin). A toxicology screen was negative for psychoactive substances. Computed tomography of the head without contrast did not show any hemorrhagic intraparenchymal or extra-parenchymal lesions or alterations in parenchymal density, either over and under the cerebellar tentorium, and showed normal flow in the ventricular system and cerebral spinal fluid spaces. Blood laboratory investigations were normal, with the exception of white blood cells at 11,650 per muL and neutrophils at 7950 per muL. On admission, the patient was started on clonazepam 5 mg/day to treat his agitation, risperidone 4 mg/day to treat his psychotic symptoms, and valproate 750 mg/day to treat his dysphoric mood. On day 3, the patient presented again with fever (38.5 C) and a worsening of his delusional symptoms. His hallucinations had worsened in intensity and frequency. He was distressed, presenting with psychomotor agitation and disorganized behavior, and tried to escape from the ward. Blood tests were again normal, with the exception of white blood cells at 16,790 per muL, neutrophils at 14,440 per muL (86%), and lymphocytes of 7.4%. Microscopic examination of the urinary sediment showed many white blood cells, red blood cells, and bacteria. Urine culture was positive for Proteus mirabilis (>100,000 colony-forming units) and Enterococcus spp (<1000 colony-forming units). Treatment with ciprofoxacin was started at 1000 mg/day. The fever disappeared on day 7, and his psychopathological condition improved. Laboratory blood investigations also improved, with a normal white cell count of 6.330 per muL, neutrophils at 3680 per muL (58.2%) and lymphocytes at 25.4%. By day 8, the delusional and hallucination symptoms had disappeared, the patient was cooperative and well orientated in time and space, and he presented with euthymic mood and normal psychomotor skills. He remembered the hallucinations and delusions as if they had been a dream he had had whilst awake, with qualitative alteration of consciousness. On the same day, because of full remission of symptoms, the patient was discharged from hospital and returned to Brazil accompanied by relatives.

capgras syndrome, delusional misidentification, psychosis, urinary tract infection

PMC7422076_01

Female

A 51-year-old healthy female without significant past medical history presented to the emergency department with severe nonradiating abdominal pain that began without an inciting event. The pain was mainly located in the epigastric region. The pain was described as sharp and was associated with nausea; multiple episodes of nonbloody, nonbilious emesis; chills; and a near syncopal episode. There were no specific alleviating or exacerbating factors, and she never had similar symptoms in the past. She denied any fever, dysuria, history of heartburn, peptic/duodenal ulcer disease, heavy nonsteroidal anti-inflammatory drugs (NSAID) use, recent illnesses, recent ill contacts, or recent travel. She denied any significant surgical history. She is a former heavy smoker and reported current moderate alcohol use and a recent increase in her stress level. The patient denied a prior history of EGD or colonoscopy. Family history is significant for coronary artery disease in both parents. In the emergency department, she was found to be hypotensive with a blood pressure of 64/48 mmHg and a heart rate of 71 bpm. Her oxygen saturation was 100% on room air. Physical exam revealed a diffusely tender abdomen. Lab tests were significant for a hemoglobin of 9.1 g/dL and a white blood count of 14.4 k/muL. Subsequently, 2 large-bore intravenous (IV) catheters were inserted and a blood type and screen were ordered. IV fluids were started along with pain and nausea control medications. A contrast-enhanced CT scan of the abdomen and pelvis revealed a large retroperitoneal hematoma with a lobulated focus of active contrast extravasation interposed between the pancreatic head and the duodenum (Figure 1). The bleeding was localized to the retroperitoneum itself and did not involve nearby retroperitoneal organs such as the pancreas, kidneys, or duodenum; however, these organs did show displacement by the hematoma. Several nearby vessels were identified as the potential source of bleeding including the distal gastroduodenal artery as well as several prominent superior and inferior pancreaticoduodenal (PDA) arteries extending from the gastroduodenal and superior mesenteric arteries, respectively. Finally, a high-grade proximal celiac artery stenosis was noted consistent with median arcuate ligament compression (Figure 2). Interventional radiology (IR) and general surgery were consulted, and a mesenteric angiogram was emergently performed to localize the bleeding for potential embolization. Mesenteric angiography confirmed median arcuate ligament compression that was well compensated through brisk extensive collateral flow from the SMA via the pancreaticoduodenal arcade (Figure 3). Embolization of an inferior pancreaticoduodenal (PDA) branch was performed with detachable 0.018-inch coils given active extravasation. Further interrogation showed the abnormal aneurysmal pancreaticoduodenal vessel, but the structure was unable to be reached given only a small network of feeding arteries measuring 1 mm or less (Figure 4). No further bleeding was identified. Although the patient's condition immediately improved following embolization, there was still potential for further hemorrhage given the untreated aneurysm. Since this, after hours, treatment was prolonged with both resuscitation and procedure time, and the patient improved clinically; she was transferred to the ICU for observation and further workup. An arterial sheath was left in place for blood pressure monitoring and potential subsequent access given an incomplete interrogation of the complex anatomy. Initial management included intravenous proton pump inhibitor, placement of the nasogastric tube, and order for the serial blood counts, and a gastroenterology consult was obtained. Later that day, the patient complained of continued epigastric abdominal pain and nausea, but vital signs remained stable. A follow-up CT scan with contrast was ordered and showed the hematoma was slightly larger containing a new bilobed 2 cm saccular area of circulating contrast. This was defined as a residual saccular pseudoaneurysm, rather than a true aneurysm, given new morphology when compared to the prior scan, and likely contained by the hematoma within the tight retroperitoneal tissues. The nearby fusiform aneurysm was not seen, presumably decompressed from rupture. The patient also required a blood transfusion given slowly dropping hemoglobin values. Although vital signs were stable, angiography was again performed given her laboratory deterioration and CT findings. The new pseudoaneurysm was identified, but unfortunately the feeding vessel remained occult after integration of multiple branches including several branches of the inferior pancreaticoduodenal artery. Given the procedure time, contrast dose, and continued relative stability of the patient, the procedure was terminated. The vascular surgery team decided against celiac release in the acute setting given the risks of the surgery and current blood loss but agreed that a median arcuate ligament release would likely be needed as an outpatient. The patient remained stable, but there was continued suspicion for a slow hemorrhage from the ruptured aneurysm. A third mesenteric angiogram was again performed on day 2 but this time with angiography of the celiac artery and gastroduodenal artery (GDA) via the high-grade celiac artery stenosis. Using digital subtraction angiography (DSA), a prominent superior PDA branch supplying the aneurysm was identified and treated with coil embolization (Figures 5(a) and 5(b)). Access from the celiac was removed, and SMA angiography demonstrated persistence of the aneurysm. Given the complexity of the PDA anatomy, cone beam CT angiography (GE Innova 540) with subsequent 3D reconstruction was performed. The 2D maximum intensity projection (MIP) images not only clearly demonstrated the PSA but also showed a second culprit posterior inferior PDA supplying the pseudoaneurysm. The gantry angle was optimized from the 3D volume rendering (Figure 6), and image overlay of live fluoroscopy allowed for quick vessel selection with the microcatheter/microwire. After verification with DSA, the vessel was treated with coil embolization (Figures 7(a) and 7(b)) thrombosing the PSA. The following day, she reported feeling well with less pain and nausea. Her hemoglobin and vital signs were stable. NG was removed, and her diet was advanced. The remainder of her hospital stay was unremarkable other than hypertension treated with lisinopril, hydrochlorothiazide, and metoprolol to aid in avoiding further rebleeding events.

PMC8197045_02

Male

A 2 months old child admitted in the month of May, 2018 into the children emergency room, of the University of Calabar Teaching Hospital with complaints of cough of one-month duration and fever of three weeks duration. Cough was distressing and worse at night. Fever was high grade, intermittent and temporarily relieved by administration of paracetamol syrup. Pregnancy was booked at a gestational age of 13 weeks. Delivery was at a gestational age of 28 weeks via emergency lower section caesarean section. Birth weight was 1.65kg. Child was admitted into special care baby unit and managed for prematurity, neonatal sepsis and neonatal jaundice on account of antepartum haemorrhage. She had blood transfusion but no exchange blood transfusion and was discharged at a weight of 1.8kg having spent a month in special care baby unit. Child was fed with infant formula and breast milk from birth. She is the second child in a monogamous setting and has a 7-year-old male sibling. The father is a civil servant while the mother is a businesswoman. Physical examination showed an acutely ill looking child, febrile with temperature of 38.6 C, mildly pale, dyspnoeic and tachypnoeic, with a weight of 3.7kg (3rd percentile), length of 50cm (below the 3rd percentile) and occipito frontal circumference - 38cm (z-score). Respiratory rate was 66cycles/minute, with SPO2 of 80% in room air. The heart rate was 186 beats/minutes with normal heart sounds. The abdomen had a tender hepatomegaly of 6cm and a splenomegaly of 6cm. Liver was 8cm below the right costal margin, soft and smooth. Spleen was 2cm below the left costal margin, and non-tender. Laboratory findings showed a PCV of 21%, random blood sugar of 4.7mmol/L, HIV screening was negative, Full blood count; Total WBC of 12.6 x 109/L, Neutrophils: 65%, Lymphocytes: 33%, Platelets: 179x109/L, Malaria parasite test: positive, Gene Xpert: negative, Mantoux test: 0 mm, Chest X-ray showed hazy opacities on the right upper and middle lung lobes, with left upper lobar opacities and pneumatoceles (Figure 1). Blood culture yielded T. ptyseos. Patient was on oxygen at 2L/min and was transfused with 60mls of settled cells. Post transfusion PCV was 25%. While on admission, patient received IV Ceftriaxone and IV gentamicin and spent 5 days during which fever subsided and respiratory rate reduced, and was thereafter discharged. One week later, patient represented and was admitted on account of the same but worsening symptoms. A diagnosis of Septicaemia with heart failure was made to rule out bronchopulmonary dysplasia and pulmonary tuberculosis. Empirical antibiotic (IV Ceftriaxone, IV Gentamicin, Suspension Azithromax) therapy were commenced. IV Furosemide and tablets digoxin was also given. On the second day of admission, IV cloxacillin was commenced, as the child remained ill and IV gentamicin discontinued. 3 days into admission, child developed seizures which was generalized tonic clonic lasting about 1-2 minutes. She had two episodes. The second episode was aborted with IV diazepam. The random blood sugar at the time was 2.9mmol/L. SPO2 was 67%. Intravenous fluid was commenced at 60% maintenance and phenobarbitone was also commenced at maintenance dose. She received blood transfusion, Nil per oral and cautious intravenous fluid, and oxygen therapy. Frusemide and digoxin were also added. Despite these measures, she was still very ill and in severe respiratory distress. CSF analysis was not in keeping with meningitis. She remained very ill, had intermittent hypothermia with subnormal temperature and died 5 days after admission. Blood culture result of sample taken on the third day of admission and received 3 days after patient s demise yielded growth of T. ptyseos. Antimicrobial susceptibility test result showed sensitivity to Amikacin, intermediate to Ceftazidime and Ciprofloxacin, and resistant to Ceftriaxone, Cefuroxime, Gentamicin, Amoxicillin-Clavulanate, Cefepime, Cefoxitin and Colistin.

septicaemia, blood culture, bronchopneumonia, case report

PMC4357676_01

Male

The patient was a 91-year-old man. He underwent a medical examination for hypertension and chronic atrial fibrillation, during which a mass was palpated through the abdominal wall. He was then referred to our hospital. Laboratory data were as follows: aspartate aminotransferase (AST) 61 IU/l (normal 5-35), alanine aminotransferase (ALT) 37 IU/l (normal 5-30), alkaline phosphatase (ALP) 334 U/l (normal 115-359), gamma-glutamyl transferase (gamma-GTP) 230 IU/l (normal 0-50), lactate dehydrogenase (LDH) 177 IU/l (normal 106-211), albumin (Alb) 3.6 g/dl (normal 3.7-5.5), total bilirubin (TB) 0.71 mg/dl (normal 0.2-1.0), and prothrombin time-international normalized ratio (PT-INR) 1.03. Child-Turcotte-Pugh grade was A. The indocyanine green retention rate at 15 min (ICG-R15) was 8%. The concentration of serum alpha-fetoprotein (AFP) was 3,600 ng/ml (normal <20) and plasma des-gamma-carboxy prothrombin (DCP), also known as protein induced by vitamin K deficiency or antagonist-II, was 93,300 mAU/ml (normal <40). No serological evidence of hepatitis B or C was seen. Contrast-enhanced computed tomography (CECT) revealed a tumor measuring 78 mm in diameter in the left lateral sector of the liver (fig. 1). HCC was suspected. The patient requested radical surgery, so left lateral sectorectomy was performed (fig. 2). The operation time was 370 min, and the amount of blood loss was 978 ml. Pathological findings revealed well to moderately differentiated HCC (fig. 3).

elderly patients, hepatocellular carcinoma

PMC4357676_02

Female

The patient was a 91-year-old woman. Laboratory data were as follows: AST 35 IU/l (normal 5-35), ALT 21 IU/l (normal 5-30), ALP 198 U/l (normal 115-359), gamma-GTP 67 IU/l (normal 0-50), LDH 162 IU/l (normal 106-211), Alb 2.9 g/dl (normal 3.7-5.5), TB 0.7 mg/dl (normal 0.2-1.0), and PT-INR 1.18. Child-Turcotte-Pugh grade was A. The ICG-R15 was 19%. The concentration of serum AFP was 1,210 ng/ml (normal <20) and plasma DCP was 209 mAU/ml (normal <40). No serological evidence of hepatitis B or C was seen. CECT revealed a tumor measuring 20 mm in diameter in segment 2 of the liver, accompanied by tumor thrombi toward the main left portal vein (fig. 4). We diagnosed HCC with tumor thrombi. The patient requested radical surgery, so left hemi-hepatectomy was performed (fig. 5). The operation time was 304 min, and the amount of blood loss was 379 ml. Pathological findings revealed poorly differentiated HCC (fig. 6).

elderly patients, hepatocellular carcinoma

PMC9210103_01

Male

A 48-year-old male was investigated in a medical unit for fever and a productive cough of 2 weeks duration. He had diabetes and history of tuberculosis (TB) bronchiectasis. Initial investigations showed a neutrophil leucocytosis, an erythrocyte sedimentation rate (ESR) of 110 mm/first hour and a chest radiograph that revealed patchy consolidation in the right-upper zone and changes consistent with post-TB bronchiectasis and fibrosis. These findings were confirmed subsequently by high-resolution chest computed tomography (HRCT). Sputum samples were negative for acid fast bacilli, TB polymerase chain reaction (PCR) and pyogenic culture. However, a blood culture was positive for K. pneumonia, and he was started on intravenous cefotaxime based on the antibiotic sensitivity pattern. He was subsequently investigated for non-specific abdominal pain with abdominal ultrasonography and a contrast-enhanced CT which showed bilobar hypo-dense liver lesions in the arterial phase that became iso-dense during venous phase. Furthermore, lesions enhancing in the arterial phase were also noted in the right lobe of prostate (Figure 1). Digital rectal examination of prostate did not reveal any significant abnormality, and his prostate-specific antigen (PSA) level was 3.2 ng/l. Upper and lower gastrointestinal endoscopy was normal and a liver biopsy or aspirate was planned. While awaiting this, he developed an acute unilateral painful red eye with rapidly worsening visual acuity. A diagnosis of acute endophthalmitis was made, and the vitreous aspirate was positive for K. pneumoniae. A subsequent abdominal CT scan showed partial resolution of the liver lesions but enlargement of the prostatic lesion that now resembled a prostatic abscess (Figure 2). Following 14 days of intravenous ceftriaxone antibiotic therapy and intravitreal injection of antibiotics, clinical and ultrasonic resolution of the hepatic and prostatic abscesses was noted, in addition to the normalisation of his inflammatory markers. Unfortunately, the endophthalmitis resulted in permanent loss of vision in the left eye, and enucleation was not performed as patients wish. He was discharged after a hospital stay of one and half months and is under follow-up as an outpatient.

klebsiella pneumonia, case report, endophthalmitis, liver abscess, prostate abscess

PMC8236777_01

Male

The first case was a 49-year-old male who presented with a history of chronic spontaneous urticaria for the past twenty-eight years. The patient's hives presented on the front and back of his body, including his feet and hips. His exacerbating factors include warm temperatures and sunlight, however, there are times that wheals appear spontaneously. Previously, the patient has tried and failed two different high dose first generation H1 antihistamines (Carbinoxamine and Cyproheptadine), as well as an H2 blocking antihistamine (Ranitidine). Subsequently, the patient was started on omalizumab (Xolair) 300 mg every four weeks, with success experienced after the third dose. The patient had been consistent with his omalizumab injections, and his symptoms were well controlled by pharmacotherapy for about 2 months. After the second dose of the Moderna COVID19 vaccine, the patient had a flare of urticaria identical to previous episodes. The outbreak occurred 16 hours after receiving the vaccination. The patient took cetirizine, and the wheals resolved within 6 hours. Since this flare up, the patient now continues to develop hives every 2 to 3 days, and his symptoms are no longer controlled with pharmacotherapy.

covid-19 vaccine, csu, chronic spontaneous urticaria

PMC6535884_01

Female

A previously healthy 11-year-old girl presented with 8 days of fever, night sweats, and subjective weight loss. Her fevers occurred every 12 hours and reached a maximum of 39.4 C. Additional symptoms included headaches, dizziness, nausea, intermittent right-sided abdominal pain, and anorexia. The patient also reported an intermittently pruritic rash on her arms. She had no respiratory symptoms, emesis, or diarrhea. Past medical history was significant for multiple episodes of bronchiolitis requiring hospitalization before age 2, varicella with severe mucosal involvement requiring hospitalization for nasogastric feeding at age 4, and hepatitis A at age 7. Growth and neurologic development were normal. The patient was born in Central America and immigrated to the U.S. 4 years prior. Exposure history was significant for consumption of unpasteurized cow milk while in Central America. A maternal uncle had been recently diagnosed with tuberculosis, but the patient had not had contact with him for more than 4 years. There was no other significant family history. Physical exam revealed a thin female (weight 33.1 kg, 22% for age; body mass index 15.5 kg/m2, 16%) with enlarged, mobile, nontender cervical lymph nodes bilaterally but no palpable axillary or inguinal lymph nodes. There were small erythematous papules on the flexor surface of her left antecubital fossa and right first metacarpophalangeal joint. She had mild abdominal tenderness most significant in the right upper quadrant, but no hepatosplenomegaly or mass. Laboratory values at admission on day of illness (DOI) 9 were notable for leukopenia, anemia, and mildly elevated C-reactive protein (CRP) (Figure 1). The erythrocyte sedimentation rate was greater than 145 mm/hr. Aspartate and alanine aminotransferase were elevated. Cerebrospinal fluid (CSF) analysis showed no leukocytes and normal protein and glucose. A fourth-generation antigen-antibody test was positive for antibodies to HIV-1. HIV RNA PCR demonstrated 294,000 copies/mL in peripheral blood and 504 copies/mL in CSF; initial CD4 T-lymphocyte count was 52 cells/mm3. Computed tomography scan demonstrated innumerable small nodules throughout the bilateral lungs and lymphadenopathy in the cervical, axillary, hilar, mediastinal, and retroperitoneal regions. The largest nodal conglomerate in the retroperitoneum measured 4.4 cm (Figure 2). Pathology of a bone marrow biopsy demonstrated hypocellularity and noncaseating granulomas. Lymph node biopsy revealed plasmacytosis and increased histiocytes with no evidence of malignancy. Acid-fast bacillus, Fite, and methenamine silver stains were negative in both tissues. Bronchoscopy revealed no significant airway edema or erythema, and no secretions. Evaluation for tuberculosis (TB) and non-TB mycobacterial infections was negative, including QuantiFERON-TB Gold, mycobacterial cultures, and/or TB PCR from sputum, bronchoalveolar lavage (BAL) fluid, lymph node tissue, blood, stool, and/or CSF. Serum antibodies to Toxoplasma gondii, Treponema pallidum, Brucella species, Coccidioides immitis, and Histoplasma capsulatum were negative. However, urine and serum H. capsulatum antigens were positive with values greater than the upper limits of quantification. Ultimately, H. capsulatum grew in fungal cultures from blood, BAL fluid, and lymph node tissue. Treatment was initiated with liposomal amphotericin B (5 mg/kg/day) on DOI 24. ART consisting of dolutegravir and emtricitabine-tenofovir alafenamide was begun on DOI 26. The patient began to feel subjectively better and appetite improved, but spiking fevers up to 42 C persisted until DOI 37. Hospital course was complicated by pancytopenia thought to be secondary to disseminated fungal infection, acute kidney injury attributed to liposomal amphotericin B, and liver enzyme elevation that was likely multifactorial. Per hospital protocol, the acute kidney injury was monitored with daily weights, serum creatinine measurements, and strict documentation of intakes and outputs. Oral itraconazole (10 mg/kg/day) was initiated on DOI 36 given improving fevers and decreasing CRP and serum H. capsulatum antigen. Liposomal amphotericin B was discontinued on DOI 46. Throughout the course of treatment, serum itraconazole and dolutegravir were monitored to ensure therapeutic levels were obtained. At discharge on DOI 47, the patient's CD4 T-cell count had improved to 215 cells/mm3 and HIV RNA PCR had decreased to 127 copies/mL.

PMC9585562_01

Male

A 15-year-old Caucasian male was transported to the TJH Regional Burn Center at UMC, Lubbock, TX after sustaining major burns 76% total body surface area (TBSA) from lighting trash on fire doused with gasoline. The patient's past medical history includes asthma and epilepsy, and home medications include Claritin-D taken twice daily and Xopenex HFA 45 mcg/inh. All other pertinent histories are noncontributory. On arrival, physical examination of the patient revealed hypothermia with a tympanic temperature of 93.6 F (34.2 C), a normotensive blood pressure of 134/82 mmHg, and a labile heart rate ranging from 106 to 146 beats/min. The patient was tachypneic with a respiratory rate of 25 respirations per minute. Skin assessment demonstrated partial to full thickness burns on 76% of the TBSA covering the head, neck, bilateral upper extremities, anterior chest, bilateral lower extremities, and back. The patient was intubated at the scene by emergency medical services (EMS) due to presence of carbonaceous sputum. Prior to arrival, the level 1 trauma team activation was initiated. Upon presentation three hours post-injury, standard burn resuscitation was administered. Additionally, the patient underwent bronchoscopy due to a secondary concern for smoke inhalation injury. Bronchoscopy findings were significant for moderate amounts of carbonaceous deposits throughout the upper and lower bronchus, worse on the right side, with grade II inhalation injury assigned. Fluid resuscitation was calculated based on the modified Parkland formula (2 cc x76 TBSA x80 kg) requiring a total of 12 L of fluid within the first 24 h of which 2.4 L of crystalloid was administered prior to arrival. Due to the circumferential burns present on the upper extremities and concern of the development of compartment syndrome, bilateral forearm escharotomies were performed. The patient required large amounts of lactated ringers to maintain minimally acceptable urine output (UO) (0.5cc/kg/hr), which led to the addition of 1.1 L of 5% albumin and 3.5 units of fresh frozen plasma (FFP). The patient received 2.5 L of fluid prior to arrival, and fluids were started at a rate of 350 mL/hour upon arrival. Per protocol, this rate was titrated up to a rate of 600 mL/hour in order to meet the goal urine output of at least 0.5 mL/kg/hour and mean arterial pressure (MAP) of at least 60 mmHg. Due to the high rate of fluid administration needed to meet this urine output goal, HAT (hydrocortisone, ascorbic acid, thiamine) was started for 48 h. Additionally, both fresh frozen plasma (FFP) and 5% albumin solution were started at a rate of 100 mL/hour for a total of 4 units of FFP and 75 gms of albumin in total over the course of 24 h. The patient's total fluid resuscitation goal was met within 24 h of admission. Maintenance fluid of D5 1/2 normal saline with 20 milliequivalents of potassium chloride at a rate of 125mL/hour was then started. Urine output was well above the goal at approximately 1 mL/kg/hr. By hospital day 2, maintenance fluids were discontinued, and urine output continued to be adequate. Treatment for the burn shock was reduced by the second post injury day (PID) and he was successfully extubated. The patient underwent a total of eight operations while admitted, beginning with escharotomies to bilateral forearms PID 0 followed by excision & grafting (E&G) to bilateral hands PID 4. No immediate postoperative complications occurred (i.e., bleeding). However, the patient developed septic shock secondary to Acinetobacter bacteremia with decreased mentation on PID 7 prompting re-intubation. The patient's vitals were significant for a temperature of 106.7 F (41.5 C), heart rate of 173 beats per minute, respiratory rate of 25 respirations per minute, mean arterial pressure (MAP) of 59 and laboratory findings were significant for PO2 of 50 mmHg, lactate of 1.98 mmol/L, and procalcitonin of 9.8 ng/ml. Blood and sputum cultures were positive for carbapenem-resistant Acinetobacter baumannii. Antimicrobial treatment was initiated with 3 g Unasyn three times daily, 1 mg/kg Eravacycline two times daily, and 15,000 to 25,000 units/kg/day Polymyxin for 14 days. By PID 9, the patient was hemodynamically stable and underwent E&G left lower extremity. He was extubated PID 10 and underwent E&G of the left upper extremity followed by E&G of the chest and abdomen PID 13. The patient's status deteriorated again on PID 14 after becoming hypotensive with BP of 70/30 and MAP as low as 38 mmHg necessitating resuscitation. Tissue cultures remained positive for A. baumanni and Pseudomonas Aeruginosa, and ciprofloxacin and meropenem were initiated. Patient developed colonic pseudo-obstruction for which a cecostomy tube was placed on PID 16. On PID 18, the patient desaturated due to mucus plugging and bronchospasm, which necessitated re-intubation and a chest tube was placed due to a left hemithorax seen on chest x-ray. The patient clinically improved over the next 24 h and was extubated with chest tube removal. The patient underwent subsequent operations including Epicel harvest from right upper extremity and right lower extremity PID 23, Epicel to right upper extremity and right lower extremity PID 24, E&G left upper extremity and left lower extremity PID 51, and E&G right lower extremity, right upper extremity, and right flank on PID 58 (Figure 1). Over the following two weeks (PID 29 to PID 43), his serum sodium was elevated and urine output gradually increased. Mean serum electrolytes were abnormal for much of this time, requiring standard replacement per day of potassium, magnesium, and phosphate as needed. Electrolyte levels were further altered due to new onset polyuria of 4.1cc/kg/hr over 24 h on PID 26, increased from an average of 2.9cc/kg/hr for the previous week. This new onset diuresis was originally attributed to the high nitrogen load from tube feeding and urine alkalization from citrate and acetate-containing medications, namely Gabapentin (acetate-containing) for neuropathic pain and Epogen (citrate-containing) to stimulate red blood cell production. However, due to the persistent hypernatremia and polyuria, the patient's care team suspected DI and considered administering desmopressin (DDAVP) orally. Serum and urine osmolality showed borderline results for confirmation of this diagnosis of 304 mOsm/kg and 460 mOsm/kg, respectively (Figure 2). Pediatric endocrinology was consulted secondary to increased urine output of 5L (3.1cc/kg/hr) in 24 h, serum sodium level of 149 mmol/L, serum osmolality of 308 mOsm/kg, and urine osmolality of 430 mOsm/kg, which further raised suspicion for DI. A single dose of 2 mcg DDAVP was administered on PID 31, yet urine output continued to increase to 5.5L (3.4cc/kg/hr) collected in the next 24 h and serum sodium level, serum osmolality, and urine osmolality remained nearly unchanged. Another dose of 2 mcg DDAVP was administered, followed by DDAVP three times daily as recommended by the endocrine team. Urine electrolytes, osmolality, and specific gravity were measured every 3 h to monitor response. The patient had massive diuresis on PID 41, 10 days after the first dose of DDAVP therapy, with UO increasing from 2.9cc/kg/hr (4.6 L/24h) to 4.3cc/kg/hr (6.9 L/24h). Therefore, the dose was increased from 3 mcg to 4 mcg three times daily. The MRI of the brain showed the pituitary gland normal in size, configuration, and enhancement. No other intracranial enhancement was of note besides a tiny bright spot on the pituitary gland, as shown in Figure 3. However, this was determined to be a benign change in the MRI. Urine output (UO) increased from 2.9cc/kg/hr (4.7L/24hr) on PID 44 to 5.0cc/kg/hr (9.5L/24hr) on PID 45, therefore the DDAVP dose was increased to 5 mcg four times daily with incremental improvement in polyuria over the next several days. The dose was decreased to 4 mcg four times daily on PID 57 with continued resolution of his polyuria. After his second dose of DDAVP on PID 59 the endocrine team recommended to hold the remaining DDAVP doses for that day and reassess for further need. There was no significant increase in the urine osmolality and serum electrolytes and osmolality remained in the normal range; therefore, the endocrine team recommended to cease DDAVP therapy on PID 60 and continue monitoring the UO. The patient continued to clinically improve and was discharged to a rehabilitation facility on PID 61.

diabetes insipidus, burn injury, central diabetes insipidus, desmopressin, nephrogenic diabetes insipidus