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PMC10280286_01

Male

A 77-year-old man presented to the office complaining of exertional chest pain. His past history was unremarkable. An echocardiogram revealed akinesia at the RCA territory with preserved left ventricular ejection fraction (LVEF) and no pericardial effusion. The patient was admitted for further evaluation, and coronary angiography (CAG) revealed diffuse three-vessel disease, with a right coronary artery (RCA) chronic total occlusion (CTO) with thrombolysis in myocardial infarction (TIMI) grade 0 flow and collateral flow from septal branches. PCI at the RCA CTO lesion was complicated by Ellis classification type II microchannel perforation during right ventricular (RV) branch wiring proximal to the lesion for additional support during CTO wiring (Figure 1). After prolonged balloon inflation at the RCA, no continued contrast extravasation was seen, and the perforation was thought to have resolved. CTO PCI was completed without any further complications, and the patient remained stable throughout the procedure. Thoracic computed tomography (CT) angiography taken the day after PCI showed no contrast extravasation, and only minimal pericardial effusion was detected. A follow-up echocardiogram was obtained, and there was no visible pericardial effusion and no other remarkable interval changes. The patient was discharged, free from symptoms, and follow-up echocardiograms and chest CT scans obtained one week and two months after PCI detected no remarkable interval change. Seven months after PCI, the patient complained of progressive dyspnea and abdominal distension and was admitted for further evaluation. The patient's symptoms prompted a follow-up CAG, which revealed no new lesions or in-stent restenosis. Also, no extravasation was noted at the previously perforated RV branch. Echocardiographic findings demonstrated a slightly increased amount of pericardial effusion and inferior vena cava (IVC) plethora, but otherwise no definite constrictive physiology was yet apparent. Laboratory findings were non-specific. Since the overall clinical picture suggested the possibility of progressive CP, he was discharged on 20 mg of prednisolone, 0.6 mg of colchicine, and diuretics. The patient visited the emergency room two weeks after discharge due to worsening abdominal distension and dyspnea. At presentation, his blood pressure was 95/60 mmHg and heart rate was 70 beats/min. His physical exam was remarkable for grade 2 pitting edema at the lower extremities, a marked jugular venous pulse, pericardial friction rub on ascultation, and a distended abdomen with shifting dullness. Laboratory findings included mildly elevated liver enzymes, with aspartate aminotransferase at 56 U/L and alanine aminotransferase at 64 U/L, and total bilirubin 1.3 mg/dl. A follow-up echocardiogram revealed pericardial thickening and adhesion at the apex and RV anterior wall, along with scanty pericardial effusion. Intraventricular septal bouncing and respiratory mitral and tricuspid valve inflow variability suggested constrictive pericarditis (Figure 2, Supplementary Video S1). Additionally, global hypokinesia resulted in a decreased LVEF of 39%. Large amounts of pleural effusion and ascites were apparent on CT scans of the chest and abdomen, the latter of which was identified as transudate by paracentesis (Figures 3A,B). Unfortunately, due to the patient's instability, right heart catheterization could not be performed. The patient underwent surgery due to increasing oxygen requirements and hemodynamic instability. Intraoperative findings revealed a thickened (5 mm) and slightly adhesive pericardium without calcifications, and a dark bloody effusion was drained after opening of the pericardium (Figure 3C). Radical pericardiectomy was performed on the anterior, diaphragmatic, and posterior pericardium under cardiopulmonary bypass, and the operation was concluded without major complications. Pathology was negative for tuberculosis, and was unremarkable except for thick fibrosis without evidence of active inflammation. After the operation, the patient experienced significant relief from symptoms such as abdominal distension and dyspnea. Postoperative care was uneventful, and the patient was discharged on diuretics. Minimal remaining septal bouncing was noted on a follow-up echocardiogram two months after surgery, but no other indicators of constrictive physiology were observed. The patient occasionally complains of intermittent chest pain, but is otherwise stable at outpatient follow-up, two years after the surgery. The patient's timeline is presented in Table 1.

constrictive pericarditis, coronary artery perforation, echocardiography, percutaneous coronary intervention, pericardiectomy

PMC2774533_01

Female

A 58-year-old post menopausal nonsmoker Caucasian female was evaluated for chronic cough of 13 months duration. The patient has a past medical history significant for hyperlipidemia, and obstructive sleep apnea. The cough was described as a dry cough and was severe enough to cause her to gag and vomit. She reported frequent nighttime awakenings due to cough. Initial work-up at another facility was reported as normal pulmonary function tests, negative methacholine challenge test, normal chest radiogram, normal chest and sinus CT scans, and a normal inspection of vocal cords, trachea, and bronchi by flexible bronchoscopy. A bronchial biopsy was performed during the bronchoscopy and results are reviewed below. She was prescribed an empiric one-week trial of prednisone which resulted in near resolution of her cough. The patient was then started on inhaled fluticasone and tiotropium without a clear diagnosis given. As a consequence, she was uncertain about the use of the inhalers and was noncompliant. The cough came back prompting another evaluation. The cough was not associated with rhinorrhea, sneezing, wheezing, dyspnea, postnasal drip, heartburn, chest pain, fever, sputum production, hemoptysis, weight loss, or night sweats. She denied ever having had exposure to immigrants or any travel outside her home state. No history of ACE inhibitors intake was noted. The patient worked with Christmas trees helping to shear, bale, and make wreaths. She has a dog at home but no other pets. She has no prior history of allergies or allergy testing. The patient did not have a history of childhood asthma, sinusitis, GERD, hayfever or tuberculosis, and no history of indoor hot tub. In addition, the patient complained of bilateral sharp chest discomfort for about 10 months, associated with the cough episodes, nonradiating and not associated with exercise, nausea, or diaphoresis. Physical examination showed normal vital signs. There was a perforated right tympanic membrane. Oropharynx showed no exudates or lesions, and normal nasal mucosa with no polyps. Lung auscultation showed normal breath sounds, and no wheezing or crackles. The heart rhythm was regular and auscultation evidenced no murmurs, rub, or gallop; her abdomen was soft with no organomegaly, extremities with no peripheral edema, and the skin showed no cyanosis or rash. Finally, no clubbing was observed. Diagnostic work up included a spirometry with FEV1 112% of predicted, FVC 111% of predicted, and an FEV1/FVC ratio of 81. The shape of the inspiratory and expiratory flow-volume curves was unremarkable. The diffusing capacity showed a DLCO of 97% of predicted. The methacholine challenge test showed that the PC20 was >16 mg/dL (normal bronchial responsiveness). Chest CT showed no infiltrates or pleural effusions, and no abnormal hilar or mediastinal lymphadenopathy. CT scan of the sinuses showed normal mucosal thickening and no air-fluid levels. A 24-hour esophageal pH probe of proton pump inhibitor excluded gastroesophageal reflux disease. CBC showed hemoglobin of 13.6 g/dL (normal range 12-15.5 g/dL), the WBC was 9.2 x 109/L (normal range 3.5-10.5 x 109/L), and differential evidenced 60% Neutrophils, 1% eosinophils, 35% lymphocytes, and 4% monocytes. Electrolytes including sodium, potassium, chloride, calcium, magnesium, and phosphorus were within normal limits. Serum creatinine and BUN were 0.8 mg/dL (normal range 0.6-1.1 mg/dL), and 12 mg/dL (normal range 6-21 mg/dL) respectively. Serology for Bordetella pertussis and Respiratory Syncytial virus (RSV) were negative. Her oral exhaled nitric oxide was elevated to 158 parts/billion (upper limit of normal <30 parts/billion). The biopsy of the left main bronchus was reviewed and revealed peribronchiolar chronic inflammation with eosinophils and thickened basement membrane (Figure 1). Sputum examination for eosinophil was not performed. Based on the normal spirometry, negative methacholine challenge test, the elevated oral exhaled nitric oxide that correlates with eosinophilic airway inflammation and bronchial biopsy, a diagnosis of chronic cough due to eosinophilic bronchitis was made. To exclude the possibility of a cardiac cause of her chest discomfort, the patient underwent an adenosine sestamibi study. During this test, she developed sudden onset of dyspnea, flushing, and bilateral wheezing (confirmed by two different clinicians) during the adenosine infusion and required hospitalization in the intensive care unit, where she was successfully treated with intravenous aminophylline.

PMC7381508_01

Male

We report a case in line with the SCARE criteria. A case of a 19 years old high secondary school student from western Sudan who was presented with right loin pain and weight loss for two months, he complains of intermittent low-grade fever, and fatigue, there was no hematuria, night sweating, cough or history of contact with a patient of tuberculosis. On abdominal examination, he was cachexic, not pale or jaundiced, the right kidney was bimanually palpable, temperature was 37.1 C, blood pressure 110/70 mmHg, and pulse rate regular at 76 beats/min. Laboratory investigations revealed hemoglobin of 9 g/dl, total leukocyte count 12,200 C/mm, and elevated erythrocyte sedimentation rate of 95 mm/hr. Renal function test and other biological investigation results were normal. Urinalysis demonstrated acidic pH, leukocytes 1+, protein nil, erythrocytes 1+, nil leukocyte casts, and negative culture of the urine for pyogenic agents. CT urography revealed right-solid mass involving the entire kidney and shows heterogeneous enhancement with multiple enlarged para-aortic lymph nodes, the lesion was suggestive of renal cell carcinoma. The urinary bladder was normal. Both ureters were normal as well as the left kidney and no hydronephrosis (Figs. 1 and 2). Considering the clinical presentation as well as laboratory and radiological investigations, a provisional diagnosis of renal cell carcinoma was made, and the patient underwent an open right radical nephrectomy through the right para-median incision using the trans-peritoneum approach. Intraoperative findings were normal peritoneum, liver and bowel. The right kidney was completely involved and mobile. Radical nephrectomy was done and the specimen was sent for histopathological examination. The patient's postoperative course was uneventful. The patient was discharged on the third day, he came after 7 days for follow up, his relatives noticed right-side weakness and accordingly CT brain was requested. It revealed features of brain abscess and surprisingly, histopathological examination of the specimen revealed microscopic features tubercles granuloma (Fig. 3, Fig. 4, Fig. 5). In concordance with the previous histopathology tuberculous brain abscess was highly suspicious. The patient was referred to the neurosurgery department where a decision of drainage was taken. PCR confirmed TB. The patient received antituberculous and continue to follow up with the neurosurgery department.

radical nephrectomy, renal cell carcinoma, renal mass, renal tuberculosis, urogenital tuberculosis

PMC4803237_01

Male

A 61-year-old man with painless ecchymotic lesions in his right upper extremity was admitted to the hospital in Isparta, Turkey, in January 2015. He was consulted to dermatology clinic, and he was given amoxicillin treatment. Punch biopsy was taken from the lesions that have revealed PG. Steroid treatment was given at 40 mg prednisolone for 2 days. The lesions were regressed immediately. He also had symptom of fever. Abdominal tomography was performed, which revealed lesions as 32x22 mm in liver and 35 mm diameter in spleen that were considered as abscess. Necrotic cells were observed from percutaneous samples, which were taken from abscess. He was given antibiotics; however, the lesions appeared again. Because immature myeloid cells were seen in blood film, he was referred to our hospital in April 2015. In his anamnesis, it was found that he was diagnosed as MDS 6 years ago and had been treated with cyclosporine at 2x100 mg for 5 years, which was stopped in January 2015. On admission, his body temperature was 38.1 C. The laboratory tests showed: hemoglobin, 9.2 g/dL; white blood cells, 5.1x103/microL; and thrombocytes, 10x103/microL. Exogenous platelet apheresis replacement was performed. He had ecchymotic lesions in both his extremities (Figure 1). Magnetic resonance imaging was performed for lesions that favor tuberculosis infection. Aspiration from liver lesion revealed the presence of Mycobacterium tuberculosis, so antituberculosis treatment was started. Bone marrow investigation revealed MDS-refractory anemia with excess blasts (7%). For lesions in bilateral upper extremities, thalidomide treatment was started at 50 mg/d. Lesions began to regress, and the patient tolerated thalidomide well, so the dose was increased to 100 mg/d. After 1 month from the initiation of thalidomide treatment, the lesions in upper extremities had disappeared (Figure 2). All of the ethical considerations were strictly handled in accordance with the Helsinki Declaration. As a standard of care/action of the hospitals of Hacettepe Medical School, it was confirmed based on patient records that the study participant gave written informed consent at the time of hospitalization and relevant diagnostic/therapeutic standards of care.

myelodysplastic syndrome, pyoderma gangrenosum, thalidomide

PMC6078553_01

Male

A 63-year-old Saudi man, known to be hypertensive, was referred from the local hospital for further management of a markedly dilated aortic arch. He had occasional chest pain, shortness of breath, and a dry cough with no hemoptysis. He reported a history of fever, night sweats, anorexia, and a weight loss of 8 kg over 4 months. There was no history of tuberculosis before, or contact with, patients with tuberculosis. A few months earlier, he was told that he had an aortic aneurysm, but had declined surgery. His temperature was 37.4 C, blood pressure 120/80 mm Hg, respiratory rate 20/min, and his pulse rate was 100/min. His body weight was 65 kg. He had no lymphadenopathy or signs of heart failure. Laboratory results showed a WBC of 5.0 x 109/L, hemoglobin 140 gm/L, and platelets of 123 x 109/L. Urinalysis and renal, hepatic, lipid, and coagulation profiles were normal. Chest x-ray revealed a huge aneurysm of the aortic arch bulging into the left lung. The descending aorta had mild-to-moderate ectasia and tortuosity. There was bilateral pleural effusion and the cardiac size was normal. Echocardiography showed a dilated aortic arch at the junction of the descending thoracic aorta and pericardial effusion. Computed tomography of the chest confirmed the huge focal dilatation of the aortic arch measuring 9 centimeters with mural thrombosis, pericardial effusion and a few calcified and enlarged mediastinal lymph nodes. Serology for human immunodeficiency virus and syphilis was non-reactive. The patient underwent surgical resection of the aneurysm and interposition of a tube graft through a postero-lateral thoracotomy approach. Intra-operatively, gross examination of the aorta revealed a huge aneurysm involving the arch as well as the proximal part of the descending aorta, another aneurysm in the middle of the descending thoracic aorta, a thickened pericardium and pleural nodules. The thoracic aneurysm was replaced from the arch down to the descending aorta. Histopathology from tissues of the aortic aneurysm, pericardium, and lymph nodes showed a granulomatous disease with central necrosis suggestive of tuberculosis. All smears were negative for acid-fast bacilli. Antituberculosis chemotherapy was started on the first postoperative day in the form of isoniazid, rifampin, pyrazinamide, ethambutol and vitamin B6. Specimens from the tissue of the aortic aneurysm, the pericardium, the lymph nodes, the tracheal aspirates, and pleural tissue grew Mycobacterium tuberculosis sensitive to isoniazid, rifampin, pyrazinamide, and ethambutol. The subsequent course was notable for excellent tolerance and adherence to antituberculosis agents. Pyrazinamide and ethambutol were discontinued after the first two months. The patient reported general improvement in his well-being, he gained weight, and had resolution of radiological findings on subsequent imaging. Repeat computed tomography of the chest and echocardiography revealed no aortic dilatation. Isoniazid and rifampin were continued for a total of 18 months. Three months after discontinuing isoniazid and rifampin, the patient was feeling well and gained 3 further kilograms. Ten months later, the patient had sudden onset chest pain and collapsed. He had very low blood pressure in a local hospital. Immediate computed tomography of the chest showed hemothorax. The patient died soon thereafter. No post-mortem was performed.

PMC7276608_01

Male

A 15-year-old Caucasian boy with no relevant medical history went to the emergency department after suffering trauma in his right hand caused by a fall forward while playing football. He presented a deformity at the base of the second finger, swelling, and painfully restricted motion. Rotational deformity of the second finger associated with radial deviation and hyperextension was found during physical examination, but neurovascular structures were intact. The X-ray (Fig. 1) showed fracture of the proximal phalanx diaphysis of the second finger of the right hand with deviation. Closed reduction under sedation was performed applying traction and ulnar deviation followed by syndactyly and immobilization with Zimmer splint. The control X-ray (Fig. 2) revealed acceptable reduction, and the patient was referred to follow-up at the outpatient consultation. The conservative treatment was kept for 25 days, with apparent fracture healing on the X-ray (Fig. 3), but the patient presented limitation on active flexion of the finger which was interpreted as a sequel of the immobilization. Thus, he was referred for physical therapy rehabilitation. Six weeks after the initial trauma, the patient was observed at the emergency department for new right-hand trauma. On examination, no active flexion of the third phalanx of the second finger of the right hand was noticed. The X-ray didnot show any new fracture (Fig. 4). Then, the patient underwent an ultrasound that revealed deep flexor tendon entrapment at the previous fracture focus. A surgery was proposed and accepted by the legal guardians. The patient was prepared to surgery. After the Bruner incision in the palm face of the affected finger, the entrapment of the deep flexor tendon within the proximal phalanx was observed (Fig. 5). Then, tenolysis of the entrapped tendon was made (Fig. 6) enabling the visualization of the bone space created by the fracture and where the tendon was trapped (Fig. 7). After that, a reconstruction of the pulleys was performed using a portion of long palmar tendon (Fig. 8 and 9) with good immediate functional result (Video 1). The X-ray performed 2 weeks later (Fig. 10), documented a good result. Four weeks later, the patient had good clinical evolution with almost complete recovery of mobility.

diaphyseal fracture of the proximal phalanx, tendon entrapment, tenolysis

PMC6852610_01

Female

During July 2017, seven paediatric burns patients between the ages of 10 months and 5 years presented with a maculopapular rash at a tertiary hospital in Gauteng, South Africa. Four of these patients were female. The rash was associated with both fever and coryza in four of the cases. The characteristics of the cases involved in this cluster are shown in Table 1. The cluster was reported to the National Institute for Communicable Diseases. Due to a concurrent measles outbreak in the province, measles was initially suspected. The rash subsequently evolved and became vesicular in two of the cases, affecting the limbs and hands in one of the cases (Figure 1). Contemporaneously, an eighth patient presented with a vesicular rash on the trunk and on both upper and lower extremities bilaterally. Of note is that this patient did not initially present with a maculopapular rash. Varicella-zoster became a differential diagnosis. As children are not routinely immunised against varicella in South Africa's public health sector, the cost, availability and resource utilisation of prophylactic varicella immunoglobulins for the cases posed a number of challenges. The natural history in the cases that developed the vesicular lesions was also atypical of the varicella-zoster infection. There was therefore a possibility of administering the immunoglobulins unnecessarily. Other possible diagnoses that were considered included enterovirus and pox infections. An investigation was initiated by the National Institute for Communicable Diseases in order to establish the cause of the illness. A composite case definition that was used to identify other cases in the ward included any patient who was admitted to the unit during July 2017, presenting with a maculopapular or vesicular rash, with or without fever or coryza. The medical records of suspected cases were reviewed using a pre-designed case investigation form. Cases were also examined for any residual or new symptoms. Further information on the history of the illness was also obtained from the caregivers of some of the cases. Blood samples were collected for serological and molecular testing using the following assays: Siemens Enzygnost measles IgM and rubella IgM EIA (Siemens, Marburg, Germany), Liaison VZV IgM CLIA (DiaSorin, Saluggia, Italy), HerpeSelect HSV-1 EIA (Focus Diagnostics, Cypress, California, United States), Genesig Herpes Simplex Virus type 1 and 2 real-time polymerase chain reaction kit (PrimerDesign Ltd, Southampton, Hampshire, United Kingdom). Vesicular fluid and scab samples were collected and submitted to the National Institute for Communicable Diseases for transmission electron microscopy using negative staining. Measles, rubella and varicella infections were excluded based on negative serological testing. Viral particles consistent with those of the Herpesviridae family were seen on electron microscopy of the vesicular fluid, while no virions were detected in the scab specimen (Figure 2). Based on these electron microscopy findings, further laboratory testing for herpes viruses was conducted, and HSV1 was confirmed based on serological and molecular testing. The medical record review of other patients in the ward identified two other cases with a documented vesicular rash. A timeline showing the sequence of events in this investigation is shown in Figure 3. Due to the initial differential diagnosis of measles, cases were given vitamin A, and measles vaccine was administered to all ward contacts below the age of 5 years. All of the cases recovered completely without any complications.

south africa, burns, herpes simplex virus type 1, paediatrics

PMC4086021_01

Female

The 38-year-old patient was offered a natural cycle IVF attempt due to critically low ovarian reserve. Her menstrual cycle was regular every 26-28 days and a general examination revealed no abnormalities. Tests prior to treatment were: day 2 FSH 16.4 IU/L, anti-mullerian hormone (AMH) 0.78 pmol/L and antral follicle count (AFC) 3. Her pre-IVF scan showed normal uterine cavity with good uterine artery blood flow (Pulsatility Index = 1.45). Her partner had a history of bilateral undescended testes resulting in an orchidopexy at the age of 3 years. This resulted in his semen analysis showing severe oligoasthenozoospermia. Her first stimulated IVF cycle with ICSI was performed in another clinic in 2007 and resulted in the term birth of healthy female. The second stimulated cycle in January 2010 yielded only one egg which produced a 5 cell embryo on day 2 which was transferred but resulted in a negative pregnancy test. Following this attempt and with results showing rising FSH levels (12.3 and 16.4 IU/L) the patient was advised to consider oocyte donation which she did not accept. In 2011 she attended our clinic for treatment and had 2 unsuccessful Modified Natural IVF cycles. The first produced 2 follicles but no oocyte was retrieved and the second produced 1 oocyte and a 5-cell embryo for transfer but no pregnancy resulted. In the current cycle the first scan scheduled at day 3 of her cycle showed menstrual endometrium, 2 follicles measuring 7 mm mean diameter on each ovary, FSH 16.4 IU/l, LH 6.8 IU/l, and oestradiol 120 pmol/L. A repeat scan on day 6 of the cycle showed early triple layer endometrium (Endometrial thickness (ET) 4.7 mm), one 10 mm follicle on the right ovary, and a 10.5 mm on the left ovary. The following scan on day 9 showed triple layer endometrium (ET 7.4 mm), a 12.4 mm follicle on the right ovary and 11.9 mm follicle on the left. The oestradiol level was 613 pmol/l and LH 7.5 IU/l. On the morning of day 11of the cycle the patient reported a strongly positive urinary LH test and felt that she might have surged the previous evening although the test was equivocal. A scan showed a triple layer endometrium 9.10 mm and a dominant follicle on the right side measuring 16.3 mm with very good peri-follicular blood flow with peak systolic velocity 19.6 cm/s. In view of this, oocyte retrieval was scheduled for later in the same day. Transvaginal oocyte collection was attempted using a double lumen Vitrolife follicle aspiration set 1.6 x 350 mm with 4 flushings of the follicle. Granulosa cells were observed in both the aspirates and flush but unfortunately no oocyte was identified. The patient gave agreement to another attempt the following morning and was given hCG 10000 IU subcutaneously. The following morning the ultrasound scan showed a regular round follicle in the right ovary with clear contents measuring 11.3 mm (Fig. 1) which had very good peri-follicular blood flow with a peak systolic velocity of 27 cm/s (Fig. 2). 24 hours after hCG injection a further attempt at oocyte collection yielded an oocyte cumulus complex. Four hours post oocyte collection the cumulus cells were denuded using hyaluronidase (Sage, Cooper Surgical) and EZ Strip pipettes (RI UK ltd) a metaphase-I oocyte was observed. This metaphase-I oocyte was transferred into Oocyte Maturation Media (Sage, Cooper Surgical, USA) for maturation in culture and checked after 4 hours. The oocyte had extruded the polar body and ICSI was performed on the resulting Metaphase-II oocyte 3/4 hours post PB observation. Fertilisation was confirmed by the presence of 2 pronuclei (Fig. 3). A 2-cell grade one embryo was transferred uneventfully on Day 2 under ultrasound guidance using Wallace SureView 23 cm (Smiths Medical International ltd). A positive betaHCG of 108 was detected 2 weeks after the ET and a viable clinical pregnancy with clear foetal heartbeat was seen on ultrasound 2 weeks later.

amh, ivm, natural cycle ivf, oocytes, peri-follicular blood flow

PMC6088479_02

Female

The patient, a 92 year-old Serbian woman, presented on 22 June 2015 with an acute episode of MI and was hospitalized. There was associated AF with rapid ventricular response, preventing stabilization of her general condition (Table 2). Past medical history: tuberculosis (1951), malaria (1960), total hysterectomy (1980) and traffic accident causing brain concussion (1982). Laboratory investigations and follow-up: electrocardiograph (ECG; 23 June 2015) (Figure 2(a)) showed ST segment elevation, in I, aVL and V1-V5 with reciprocal changes in the inferior leads; anterior wall infarction. AF with rapid ventricular response. The patient was given intravenous amiodarone (anti-arrhythmic). Homeopathic intervention: on 25 June 2017, homeopathic therapy was given in the form of a few sips of water dose of Arnica montana 30C. A few minutes later, the cardiac monitor showed a sinus rhythm, confirmed by the ECG on 26 June 2017(Figure 2(b)). She was moved from the intensive care unit to a hospital room at this point, and homeopathy was not repeated. On 27 June 2015, she went into AF with rapid ventricular response again and was re-admitted to the intensive care unit. On repetition of Arnica 30C (on 28 June 2015), however, the sinus rhythm appeared within a few minutes, and she was discharged from the hospital the next day. She stabilized and stayed well for six more months after being discharged from the hospital, evidenced by the stability in ECG. On 10 November 2015, she had another MI attack. However, this time there was no AF, and she was stable with immediate administration of Arnica 200C, despite the LVEF being only 15%. She stayed in the intensive care unit for a day. Holter ECG showed a sinus rhythm. After the last episode, she has stayed well hitherto, and the last investigation performed was on 10 April 2017. The echocardiography (Figure 2(c)) shows a stable cardiac state, despite remodelling of myocardium and reduced left ventricular function. She is not on any anti-arrhythmic drugs.

cardiovascular, heart failure, homeopathy

PMC10225563_01

Male

A 56-year-old man going wild fishing nearly every day complained of a blurred vision and an inferior visual field defect in the right eye for one day. At presentation, he denied any systemic symptoms, but mentioned an insect-bite-like skin induration in his left leg two or three days prior to his visual symptom onset. His past medical history was remarkable. Ophthalmic examination in the medical record of local hospital showed a visual acuity of 20/20, no conjunctival injection, clear cornea, quiet anterior chamber, normal pupil size and light reflex, and swollen optic disc in the right eye, and normal left eye. He was diagnosed as ON in the right eye, immediately admitted to the local hospital, and treated with intravenous injection of dexamethasone 10 mg once per day for seven days. However, his right eye vision progressively deteriorated to 20/50 during steroid therapy. Hence, the patient refused further steroid therapy. Unfortunately, 3 days after the cease of steroid therapy, he suffered from a high fever of 39 C and painful subcutaneous masses in the left groin. He then came to other hospitals for consultation, where physical examination revealed an eschar on the lateral skin of his left leg, and enlarged lymph nodes in the left groin which was confirmed by B-type ultrasound. His white blood cell count was 10.5 x 10 cells/L with neutrophils 88.3% (higher), lymphocytes 6.8% (lower), monocytes 4.6%, basophil 0.3%, and eosinophils 0%, red blood cell count 4.76 x 10 cells/L, platelet 118 x 10 cells/L. Activated partial thromboplastin time was 28 seconds (normal), thrombin time 18 seconds (normal), prothrombin time 10.4 seconds (normal), fibrinogen 2.13 g/L (normal), and D-Dimer 0.52 mg/L (normal). Erythrocyte sedimentation rate was 3 mm/hour (normal), C reactive protein was 12 mg/L (higher). Serum IgM was 3.333 g/L(higher), whereas serum IgG, IgA, Complement C3 and C4 were all within normal limits. Serum tests for pathogens including treponema pallidum, mycobacterium tuberculosis, herpes simplex virus, varicella-zoster virus, cytomegalovirus, hepatitis B virus, hepatitis C virus, HIV, Dengue virus, novel bunyavirus, and toxoplasma gondii, as well as antinuclear antibodies, and antineutrophil cytoplasmic antibodies, were all negative. CBA revealed a triple negative test result for serum AQP-4 Ab, MOG-Ab, and GFAP-Ab. Serum test for Orientia tsutsugamushi by mNGS was positive. He was then diagnosed as scrub typhus and ON, and treated with doxycycline 100 mg twice per day, and omadacycline 300 mg per day for 6 days. His fever and diffuse shin rash which appeared on the day of antibiotic therapy rapidly resolved after treatment. However, his vision in the right eye continuously deteriorated to hand motion. The patient was then referred to our neuro-ophthalmology clinic for further consultation. At presentation, physical examination confirmed the skin eschar on the left leg (Figure 1A), and B-type ultrasound revealed enlarged lymph nodes in both groins (Figure 1B). Ophthalmic examination revealed his right eye had a visual acuity of light perception, clear cornea, quiet anterior chamber, dilated pupils of 6 mm with sluggish light reflex, clear lens, and swollen optic disc (Figure 2A), and his left eye was normal (Figure 2B). Intraocular pressure was normal in both eyes. Further serum tests showed anticardiolipin IgM antibody of 154.4 GPL/ml (higher), beta-2-glycoprotein-I IgM antibody of 112.3 SMU/ml (higher), and C reactive protein 1.1 mg/L (normal). TBA revealed granular intracytoplasmic and circular perinuclear immunofluorescence staining in Purkinje cells (Figure 3, arrow) of monkey cerebellum tissues when they were incubated with the serum samples (diluted as 1:100) of the patient. Orbital MRI showed normal optic nerves with no enhancement (Figures 4A, B). His diagnosis of unilateral ON secondary to scrub typhus was confirmed, and sequential intravenous methylprednisolone 500 mg per day for 3 days, 240 mg per day for 3 days, and 120 mg per day for 3 days, tapered by oral prednisone, together with doxycycline 100 mg twice per day, were prescribed. His serum titers of anticardiolipin IgM and beta-2-glycoprotein-I IgM antibodies decreased to 88.6 GPL/ml and 66.0 SMU/ml respectively one week later. Another one month later (11 weeks after the onset of ON), his right eye vision was gradually improved to 20/80, ophthalmic examination showed a pale optic disc (Figure 2C), and visual field test showed a tunnel field (Figure 2D) in the right eye. Repeated serum test revealed a further decrease in titers of anticardiolipin IgM and beta-2-glycoprotein-I IgM antibodies to 25.5 GPL/ml and 26.5 SMU/ml, respectively. The patient was followed up by telephone five months after the onset of ON, and he reported a stable visual acuity in the right eye, though steroid and doxycycline therapy already ceased.

orientia tsutsugamushi, anticardiolipin antibody, beta-2-glycoprotein-i antibody, metagenomic next-generation sequencing, optic neuritis, scrub typhus

PMC8433240_01

Female

This is a 21-year-old female with a history of chronic headache for several years with Chiari decompression surgery performed in 2017 and latero-cervical adenopathy diagnosed as lymph node TB on bacteriological, molecular and histological arguments in 2019. GeneXpert MTB/RIF performed on the cervical lymph node came back positive for TB, without resistance to rifampicin. She was then treated at another institution according to the national protocol which includes quadritherapy with isoniazid, rifampicin, ethambutol and pyrazinamide for 2 months followed by bitherapy with isoniazid and rifampicin for 10 months (2RHZE/10RH). The evolution was then marked by the disappearance of the lymph nodes after one year of treatment. Six months after the end of treatment, the patient presented to the emergency room with severe headaches. Otherwise, no cough, chest pain, fever, or loss of appetite was reported. The patient noted no signs of trismus or difficulty breathing. She reported no known allergies and had no history of smoking or drinking alcohol. On admission, physical examination revealed a body temperature of 36.6 C, a heart rate of 90 beats/min, and a blood pressure of 117/75 mmHg. Palpation of both sides of the neck revealed no tenderness and no lymph nodes were noted. Examination of the oral cavity revealed no pathologic findings, and no posterior pharyngeal wall projections were observed. The lungs were clear on auscultation and no neurologic deficits were noted on initial clinical examination. The biological workup showed hemoglobin at 12.6 g/l; white blood cell count at 4.8 G/l; and C-reactive protein at 0.8 mg/l. In addition, serologies for human immunodeficiency virus (HIV), hepatitis B, and hepatitis C were negative. A cerebral CT scan performed as part of the etiological diagnosis fortuitously revealed a peripherally enhanced collection in the retropharyngeal area after injection of contrast medium measuring 19 x 21 mm, associated with an adjacent necrotic adenopathy measuring 10 x 06 mm. (Fig. 1). A cervical MRI was realized later and confirmed the presence of the retropharyngeal collection. (Fig. 2). The abscess was drained under local anesthesia. 02 milliliters of pus were aspirated. The specimen was sent for bacteriological analysis for Mycobacterium tuberculosis complex (MTC) and banal germs as well as for pathological study. A molecular study using GeneXpert MTB/RIF (Cepheid, Sunnyvale, CA, USA) resulted in detection of MTC with detection of rifampicin resistance in less than 2 h. In response to this rifampicin resistance, we performed other molecular tests, including GenoType MTBDRplus VER. 2 and GenoType MTBDRsl VER.1 (Hain Lifescience GmbH, Nehren, Germany) on the pus to confirm rifampicin resistance and also to investigate resistance to other anti-TB drugs. It should be noted that this technique is not validated on extrapulmonary specimens directly, although many studies have showed a good correlation with the usual resistance screening methods. The MTBDRplus VER. 2 showed resistance to both rifampicin and isoniazid, while MTBDRsl VER.1 showed resistance only to aminoglycosides. Direct examination after special Ziehl-Nielsen staining was positive and cultures on Lowenstein-Jensen (LJ) solid medium and Mycobacteria Growth Indicator Tube (MGIT ) liquid medium were positive after 32 days and 12 days respectively, thus confirming the molecular diagnosis. A treatment was initiated on the basis of molecular data. The histopathological study confirmed the molecular diagnosis by showing epithelioid and gigantocellular granulomas with caseous necrosis, without histological evidence of malignancy. Subsequently, the patient was put on a long-term protocol consisting of 6 months of bedaquiline, levofloxacin, linezolid, clofazimine, and cycloserine and 12-14 months of levofloxacin, linezolid, clofazimine, and cycloserine. After 1 month of treatment, the antibacillary drugs appear to be well tolerated, and the patient is still being monitored.

genexpert mtb/rif, genotype mtbdrplus, genotype mtbdrsl, multidrug-resistant, retropharyngeal abscess

PMC3279322_01

Male

A 68-year-old, HIV negative was affected by tubercular (TB) epididymitis. His previous medical history was remarkable for a total gastrectomy with Roux-en-Y gastric bypass procedure performed five years before, due to gastric cancer. His renal and liver function was normal. His weight was 65Kg. He was treated with standard oral anti TB therapy including isoniazid 300 mg daily, rifampin 600 mg daily, ethambutol 1200 mg daily and pyrazinamide 2000 mg daily, vitamin B6 300 mg daily. His chronic medications were: enalapril 20 mg daily, amlodipine 5 mg daily, ticlopidine 500 mg daily. Therefore plasma concentrations of anti TB drugs were measured after seven days of drug intake in the hospital. Plasma samples were collected before the drug intake to measure Ctrough and after 2 hours to measure Cmax (peak plasma concentration). We found very low Cmax and AUC0-24 levels of isoniazid (0,395 mg\L and 4.75 hr*mg/L respectively), not attributable to patient's anti-hypertensive and anti-tubercular drug-drug interaction. The results of plasma concentrations, AUC0-24 and the therapeutic expected range are shown in the following table. The patient obtained slow clinical improvement.

PMC3279322_02

Female

A 65-year-old HIV negative woman was affected by pulmonary tuberculosis. She underwent a partial gastrectomy for a gastric ulcer 15 years earlier. Her weight was 39 Kg; she was treated with standard anti TB therapy including isoniazid 250 mg daily, rifampin 600 mg daily, ethambutol 1000 mg daily and pyrazinamide 1000 mg daily, vitamin B6 300 mg daily. The drugs were administered intra venous (iv) in the first 15 days and oral subsequently (pyrazinamide and vitamin B6 were always administered orally). No other drugs were taken by this patient. We studied the plasmatic drugs concentration in the course of iv and oral therapy. Plasma samples were collected before the daily drug intake to measure Ctrough and after 2 hours and 5 hours to measure Cmax. The results of plasma concentrations, AUC0-24 during oral therapy are shown in the table. During iv therapy the measured AUC0-24 was very similar from the one reported in the course of oral treatment: isoniazid 26.70 hr*mg/L, rifampin 154.87 hr*mg/L, ethambutol 32.48 hr*mg/L. The patient obtained adequate clinical response.

PMC3980151_01

Female

We report a 54-year old Caucasian female patient who was involved in a car accident. She was the driver of the car, and was hit by another car on the driver's side. The fellow passenger of the car was seriously injured and was treated in hospital for traumatic brain injury. Both of the passengers were wearing their seatbelts correctly, and the female patient did not lose consciousness. At the first hospital, where the female patient underwent pelvic X-ray, an acetabular fracture on the left side was detected. The patient was then transported to the second hospital, where a CT scan of the pelvis was performed. This revealed a multiple-fragment fracture of the left acetabulum. The patient was later given a tetanus vaccination and a trans-urethral catheter was put in place. At this time, urine did not show any signs of macroscopic hematuria. Later, following communication via telephone, the patient was brought to our institution, a level 1 trauma-center, by helicopter. Because of the nature of the accident, with a high-energy trauma, complete polytrauma management was performed. During the body check, under pain in the left part of the pelvis, a moderate tension of the lower parts of the abdomen was observed. The ultrasound did not reveal any free abdominal fluid. Blood count showed normal values. In addition to the multiple-fragment fracture of the left acetabulum, the CT scan revealed an aneurysm of the infra-renal aorta with a dissection from the height of the second lumbar vertebral body to the iliac artery (Figures 1 and 2). Because of the aneurysm, the patient required operative vascular surgical intervention on the day of admission. During this operation, a vascular substitute of the aorta with a 14/7 mm Dacron-Y-prosthesis was used to reconnect the superior mesenteric artery. Nine days postoperatively, the open reduction and internal fixation of the acetabular fracture was performed without any incidence. Nineteen days post trauma, the patient was discharged from the hospital in good general condition. She did not show any signs of vascular deficits of the lower limbs or in the abdominal organs.

computed tomography scan, high-energy trauma, missed injury, traumatic aortic dissection

PMC7519989_01

Female

A 60-year-old woman with a medical history of type 2 diabetes mellitus, papillary thyroid cancer status post resection, and hypertension presented to a referring hospital with worsening headaches and visual disturbances. For four months prior to her presentation, she had experienced intermittent unilateral, pulsating headaches as well as visual disturbances in the right eye. Upon arrival to the emergency department, she was febrile and noted to have meningismus. CBC revealed white blood cells at 9,800/L, hemoglobin at 12.9 g/dL, and platelets at 223,000/uL. Lumbar puncture was performed with a cerebrospinal fluid (CSF) profile demonstrating colorless fluid, total nucleated cells 43/mm3, red blood cells 4/mm3, glucose 134 mg/dL, total protein 50 mg/dL, and an opening pressure of 21 cm H20. CSF herpes simplex virus 1/2, West Nile virus, cytomegalovirus, enterovirus, varicella zoster virus PCRs, venereal disease research laboratory (VDRL), and coccidioides antibodies were negative or nonreactive, respectively. Serum HIV 1/2 antibodies, QuantiFERON-TB Gold, and autoimmune panel consisting of antinuclear antibody, rheumatoid factor, anti-mitochondrial antibody, and macrophage 2 antibodies were also nonrevealing. Magnetic resonance imaging (MRI) of the brain was obtained at the time which showed acute-to-subacute thrombosis of the right transverse sinuses (Figure 1). Given her constellation of symptoms and negative infectious and autoimmune workup, she was initially treated for aseptic meningitis and discharged home with warfarin anticoagulation for the thrombosis. Her symptoms did not fully resolve, however, and she was readmitted one week later to the hospital for further evaluation and workup. On readmission, her CBC demonstrated elevated white blood cells at 17,000/L (38% polymorphonuclear cells, 34% lymphocytes, and 23% variant lymphocytes). Due to the presence of variant lymphocytes noted at that time, a peripheral blood smear was obtained which revealed precursor B-cells and 30% circulating blasts consistent with B-cell acute lymphoblastic leukemia (ALL). A repeat lumbar puncture was performed with CSF profile demonstrating total nucleated cells 728/mm3, red blood cells 0/mm3, glucose 93 mg/dL, and total protein 42 mg/dL. CSF flow cytometry demonstrated 97% blasts expressing CD34, CD19, bright CD10, and dim CD33 consistent with CNS involvement. After consultation with hematology, the patient was started on the ALL202 protocol with cyclophosphamide, daunorubicin, vincristine, methotrexate, cytarabine, and imatinib (given Ph chromosome positivity) as well as intrathecal methotrexate. During her hospitalization, her dural sinus thrombosis was treated with therapeutic-dosing enoxaparin at 1.5 mg/kg/day (100 mg). During the course of her ALL treatment, the patient experienced repeated episodes of thrombocytopenia with clinical concerns for subarachnoid hemorrhage. After a year and a half of anticoagulation with enoxaparin, a follow-up MRI was obtained which demonstrated stability in the thrombosis since initial diagnosis. Because of the chronicity of the thrombus and the ongoing bleeding concerns, enoxaparin was discontinued. The patient underwent subsequent brain imaging during the course of her ALL treatment which did not demonstrate any increase in size of the dural sinus thrombosis despite lack of anticoagulation.

PMC4828576_01

Female

A 4-year-old girl banged the back of her head and neck while bathing. She lost conscious for few seconds, and was agitated during the postconcussion period. After 72 hours her score on the Glasgow Coma Scale (GCS) was 8 (eye opening=3, verbal=4, and motor=1), and she had bilateral reactive pupils, generalized symmetrical hypotonia, intact sensation, and intact knee and ankle reflexes. The plantar response was bilateral flexor, and she reported backache. A CSF examination showed pleocytosis (70 cells/microL) with mild elevation of protein (50 mg/dL), negative CSF oligoclonal bands, and negative serum neuromyelitis optica-immunoglobulin G antibodies (ELISA/dilution 4x). MRI of the cervical spine and brain confirmed a diagnosis of ADEM (Fig. 1). She showed a marked improvement after pulse steroid therapy with methylprednisolone sodium succinate (Solu-Medrol , Pfizer Inc., Belgium) at 30 mg/kg daily for 3 days. She was continued on oral prednisolone that was subsequently tapered over a 3-week period. A 3-week follow-up MRI examination showed regression of the disease process in terms of size, number, and mass effect of lesions. After 2 months she exhibited a complete clinical recovery, and normal neurologic findings. Posttraumatic ADEM is rarely reported. An abnormally low GCS score at 24 hours or longer after head trauma is associated with an unfavorable prognosis. In the present case the GCS score remained low at 3 days posttrauma. In our case brain demyelination occurred 72 hours after TBI. An animal study found that neuroinflammation plays a key role in the pathophysiology of brain damage following TBI. Biphasic breakdown of the blood-brain barrier after TBI has been reported to first appear immediately after the primary insult, with the permeability peaking within a few hours and then subsequently improving. Delayed injury cascades typically peak at 3-7 days after TBI, and lasts from days to years. Persistent inflammation and ongoing white-matter degeneration lasting many years after a single TBI have been reported in humans. PET imaging in humans using a ligand that binds to activated microglia revealed increased microglial activation for up to 17 years after TBI. Multiple or single extensive lesions on MRI in ADEM syndrome may be associated with disability. This contrasts with our case, since she recovered completely despite having multiple lesions. It is unclear whether the complete recovery in our case was due to the underlying etiology or to the early application of treatment. A previous study found a mortality rate of 20% with a high incidence of neurologic sequelae in patients who survived postmeasles ADEM.

PMC6735298_01

Male

A 57-year-old African American male with medical history of AIDS presented with progressively worsening cough, shortness of breath, intermittent fever, and night sweats for about 10 months. He also reported 60-pound weight loss during that time. However, he was on a liquid diet because of difficulty of swallowing due to extensive oral lesions and odynophagia. The patient reported that he was off from HAART therapy for approximately one year but restarted treatment 14 months ago. He was on cobicistat, elvitegravir, emtricitabine, and tenofovir. However, he was noncompliant with his treatment. He had a biopsy of oral lesions done prior to the admission, showing KS. Physical examination was significant for diffuse dark purple patches and plaques involving the face, back, arms, legs as well as hard palate and gums (Figures 1and 2). On chest examination, he had decreased air entry in the right lower lung fields. Complete blood count was significant for normocytic anemia and thrombocytopenia. The patient's absolute CD4 count was 27 cells/microliter. Chest x-ray (Figure 3) and subsequent chest computed tomography (Figure 4), showed moderate right lung pleural effusion with scattered bilateral diffuse infiltrates and mild mediastinal and retroperitoneal lymphadenopathy. Immediately after the admission, the patient continued to deteriorate with worsening hypoxemia, requiring 15-liter oxygen with nonrebreather mask and transferred to the ICU for acute respiratory failure. He underwent thoracentesis which revealed hemorrhagic pleural fluid, negative for infection or malignancy. Infectious etiology has been excluded after blood culture and sputum culture were found to be negative for bacterial, viral, or fungal infections. Pulmonary tuberculosis, Coccidioidomycosis, pneumocystis jiroveci, and syphilis were also ruled out. Other malignancies which can involve lung and pleura in patient with AIDS (such as pulmonary lymphoma and lung cancer) were less likely as CT scan of chest, abdomen, and pelvic did not show any lymphadenopathy and pleural effusion cytology found to be negative for any malignant cells. After exclusion of Infectious etiologies, and other malignancies, the patient was diagnosed with poor risk and extensive KS (T1I1S1). He was immediately started on chemotherapy with paclitaxel along with HAART. Dexamethasone 10 mg was also added at the time of chemotherapy administration for prevention of hypersensitivity reaction. Since receiving the chemotherapy, his condition has significantly improved with near complete resolution of the pleural effusion, oral and skin lesions. The patient was able to tolerate oral diet and has regained 30-pound weight. He completed total six cycle of chemotherapy with paclitaxel 190 mg with no significant side effects.

aids, chemotherapy, haart, kaposi sarcoma

PMC9749051_01

Male

A previously healthy 10-month-old African infant developed high-grade fever and emesis with a subsequent widespread urticarial rash and bilateral non-secretive conjunctivitis. He was admitted to our tertiary care hospital after 4 days of persistent fever. At the physical examination, the infant presented marked irritability with tense, wide and bulging anterior fontanelle, shallow breathing and a widespread macular erythematous rash on trunk and limbs. Brain ultrasounds did not detect intracranial bleeding or meningitis signs. Blood tests evidenced a remarkable increase of inflammatory markers [C-reactive protein (CRP) 32.08 mg/dl, procalcitonin (PCT) 97.7 ng/ml], neutrophilic leucocytosis, NT-pro-BNP (92,230 pg/ml) and D-dimer (2547 ug/l FEU) elevation, and a high ferritin value (810 ng/ml). SARS-CoV-2 IgG antibodies were positive, while RT-PCR for SARS-CoV-2 on nasopharyngeal swab was negative. Echocardiography evidenced slight coronary arteries dilatation and hyperkinetic left ventricle, with normal systolic function. Empiric antibiotic and antiviral treatment was started. Clinical and laboratory findings suggested a PIMS-TS diagnosis. Therefore, a single 2 g/kg dose of intravenous immunoglobulin (IVIG) was administered, followed by intravenous continuous infusion of anakinra (10 mg/kg qd). Moreover, a prophylactic antithrombotic therapy with enoxaparine at 100 UI/kg qd was started because of D-dimer elevation and initial coronary arteries dilatation, according to American College of Rheumatology clinical guidelines for PIMS-TS. Despite this prompt intervention, 24 h after admission, a neurological deterioration was observed with drowsiness alternating with extreme irritability. Brain computed tomography (CT) reported an initial cerebral oedema, with meningeal and cerebral herniation from the anterior fontanelle. The patient continued to get worse and severe hypotension rapidly occurred requiring the admission to the intensive care unit (ICU), hemodynamic support with amines and mechanical ventilation. In order to treat cerebral oedema, dexamethasone and mannitol were administered intravenously. Subsequent cardiological evaluation described increased coronary arteries ectasia. On day 7 from admission, a new fever rise, and a leucocytosis rebound occurred during the slow tapering of anakinra, therefore, the immunomodulatory regimen was re-intensified. A second 2 g/kg dose of IVIG followed by three boluses of methylprednisolone was administered. After the maximization of treatment, patient's clinical conditions gradually improved. He was weaned from ventilation, sedation and vasoactive support. Antibiotics and antiviral therapy were discontinued since all infectious tests resulted negative (aerobic and anaerobic bacteria and fungal blood cultures; Cytomegalovirus, Epstein-Barr virus, Adenovirus, Neisseria meningitidis, Streptococcus pneumoniae, Escherichia coli, Klebsiella pneumoniae, Listeria monocytogenes, Streptococcus agalactiae, Haemophilus influentiae, Human Herpesvirus-6, Human Herpesvirus-7, Enterovirus, Herpes Simplex virus-1, Herpes Simplex virus-2, Parvovirus on blood samples by real-time polymerase chain reaction (RT-PCR); QuantiFERON for the detection of Mycobacterium tuberculosis). On day 10, the boy was back at his neurological baseline, with a normal anterior fontanelle. He was persistently afebrile, and the rash completely disappeared. Inflammation indexes slowly decreased, and the patient was moved to the paediatric ward. Dexamethasone regimen was suspended. Two weeks after the admission, the baby presented peeling of the extremities and remarkable thrombocytosis. Right coronary artery (RCA) demonstrated a residual deep aneurismatic remodelling (+5.5 SD). Anti-platelet therapy was started, while enoxaparin was discontinued. Anakinra was slowly tapered and shifted to subcutaneous administration, with no fever relapse. Brain magnetic resonance imaging (MRI), performed on day 14, showed periventricular hyperintensities without restricted diffusion (Figure 1). Slight cerebral and cerebellar trophism reduction was observed, with mild peri encephalic subarachnoid spaces enlargement. Angiography, venography and post-contrast scan were normal. Coronary arteries dilatation regressed at its normal size (proximal RCA: +2.2 DS; common trunk of left coronary artery +2 DS; proximal anterior interventricular coronary artery: +1.32 DS; circumflex branch of left coronary artery +1.2 DS) within 2 weeks after its peak (Figure 2). As regards neurological status, the infant presented a regular development without sequelae.

kawasaki disease, mis-c, pims-ts, neurological manifestations

PMC10085002_01

Unknown

The present study was approved by the Ethics Committee of University of Khartoum, Khartoum, Sudan (5/2018). This study adheres to the Declaration of Helsinki (1964). Written informed consents were obtained from all participants in the study or legally responsible guardians for participants less than 18 years old. Genomic DNA was isolated from blood samples with the large volume kit for the MagNA Pure system (Roche, Almere, The Netherlands) according to the manufacturer's descriptions. The isolated DNA was stored at -20 C. Genomic variants of TLR1 (rs5743604, rs5743611, rs5743618, rs76600635, rs5743551, rs5743557, rs5743565, rs5743566, rs5743580, rs5743594 rs4833095, rs5743595, rs5743596); TLR2 (rs1816702, rs5743704 rs5743708, rs7656411, rs11938228, rs893629, rs1898830, rs121917864, rs4696480, rs3804099, rs5743699 rs3804100); TLR4 (rs7869402, rs1927907, rs1927911, rs1927914, rs6478317, rs55912718, rs5030719, rs10759931, rs10759933, rs2770150, rs1554973, rs11536878, rs11536879, rs7873784, rs11536889, rs4986790, rs4986791, rs11536897, rs11536898); TLR6 (rs3796508, rs5743810, rs5743831, rs1039559, rs6531670, rs5743788, rs5743794); TLR8 (rs4830805, rs4830808, rs3747414, rs3761624, rs1548731, rs2109134, rs3788935, rs1013150, rs5744068, rs3764879, rs5744080, rs3764880, rs17256081, rs5741883, rs2407992, rs178998); TLR9 (rs5743836, rs164637, rs352139, rs352140, rs352143, rs352162, rs352165, rs352167, rs187084); and TLR10 (rs4129009, rs7694115, rs10856839, rs11466645, rs4274855, rs11096955, rs11096956, rs11096957, rs7698870, and rs10776483) genes were detected by PCR followed by restriction enzyme fragment analysis (PCR-RFLP) (Figures 1 and 2). All PCR primers are stated in Table 2. Each of the PCRs consisted of a pre-denaturation step of 4 minutes at 94 C and 40 cycles each of 30 seconds denaturation at 94 C, 30 seconds annealing at 55 C and 30 seconds elongation at 72 C. This was followed by a post-elongation step of 7 minutes at 72 C. Restriction endonucleases were selected using the NEBcutter software (http://nc2.neb.com/NEBcutter2/). Restriction endonucleases were obtained from Fermentas (st. Leon-rot, Germany), and Roche (Penzberg, Germany) and were used as described by the manufacturer. Restriction fragments were visualized by electrophoresis on 2% agarose gels (Hispanagar, Sphaero Q, Leiden, The Netherlands). The criteria for the selection of SNPs for this study were based on their previously reported to change the level or function of corresponding gene products and influence susceptibility/resistance to infections. Also, the selection was based on the publically available information on the polymorphisms of TLR genes available in the 1000 Genomes project for the South Asian population (http://www.internationalgenome.org). The mean age of the patient population and the control population were compared by the unpaired t-test. Gender, occupation and BCG-vaccination status between the patient and control population were compared with the Fisher exact test. Verification of Hardy-Weinberg equilibrium (HWE) was performed with Pearson's chi2 test. The effect of the TLR1; TLR2; TLR4; TLR6; TLR8; TLR9; and TLR10 polymorphisms on susceptibility to tuberculosis were assessed with the Fisher exact test. P-value of <0.05 was deemed statistically significant. All statistical analyses were performed using SPSS for Windows v11.0 statistical analysis software. This study was in accordance with the principles of the Helsinki Declaration (1964). This study was in accordance with the principles of the Helsinki Declaration (1964) This study was in accordance with the principles of the Helsinki Declaration (1964)

pcr-rflp, toll-like receptors, tuberculosis

PMC8221701_01

Male

Our patient is a 67-year-old Spanish-speaking male with history of hypertension, hyperlipidemia, and chronic bilateral osteoarthritis of the knees, who was admitted to our hospital for anasarca and shortness of breath. Over the 3 months prior to initial presentation, he noticed worsening bilateral lower extremity pitting edema, abdominal swelling, and orthopnea. He also endorsed having nausea, vomiting, and diarrhea. Furthermore, he reported making less urine than before, accompanied by urine frothiness. On initial examination, his blood pressure was 168/67 mm Hg. He had notable anasarca and a brain natriuretic peptide in the 2000s. There was 4+ pitting edema of his lower extremities up to the thighs. His lungs were clear and there was no respiratory distress. Initial urinalysis showed elevated urine protein of >500 mg/dL with 5 to 10 white blood cells/high power field (WBC/HPF) and 20 to 30 granular casts/HPF. His baseline serum creatinine (SCr) in 2018 was 0.5 to 0.6 mg/dL, but his SCr on initial admission was 2.1 mg/dL. Albumin was 2.0 g/dL, and urine protein:creatinine ratio (UPCR) was 6132 mg/g. Extensive proteinuria workup was done, revealing of 7 g protein/24 h, 3600 mg/24-h albuminuria. The proteinuria was mostly albuminuria nearly 60% with 40% of proteinuria being non-albumin proteinuria. Further workup, including HIV, hepatitis B, hepatitis C, antinuclear antibody, rapid plasma reagin, anti-Rho, double-stranded DNA, and complements C3 and C4, was all negative or within normal limits. Serum and urine protein electrophoresis showed no monoclonal spikes. Renal ultrasound demonstrated normal cortical echogenicity and contour for both kidneys, with right measuring 13.2 cm and left measuring 13.0 cm. A percutaneous sonographic guided renal biopsy was done and was composed of renal cortex and contained at least 33 non-sclerotic glomeruli. The glomerular capillary loops were mildly thickened and exhibited segmental subtle spikes and pinholes. Podocytes appeared reactive. There was no mesangial or endocapillary hypercellularity. There were no large endocapillary deposits, necrotizing lesions, segments of sclerosis, or crescents. There was patchy acute tubular injury associated with mild patchy interstitial inflammation associated with foci of tubulitis and scattered eosinophils. There was mild interstitial fibrosis/tubular atrophy (~15%). Immunofluorescence studies demonstrated segmental granular glomerular capillary wall staining with immunoglobulin G (IgG, trace), immunoglobulin M (IgM, trace), C1q (trace-1+), kappa (trace), and lambda (trace) light chains. There was no extra-glomerular staining. The M-type phospholipase A2 receptor (PLA2R) stain was negative. Electron microscopic analysis demonstrated diffuse podocyte foot process effacement with frequent microvillous transformation and condensation of actin cytoskeletal filaments. Glomerular basement membranes were variable thickening with segmental subepithelial and intramembranous electron lucencies and subepithelial remodeling (spike/pinholes) and showed rare small granular subepithelial and intramembranous deposits. Minimal mesangial electron densities were present. No deposits displayed any significant fibrillary or microtubular substructure. There were no tubuloreticular inclusions or immune complex-type deposits present in any other location (see Figure 1). Diagnosis of MN (stage IV of IV) and mild AIN was rendered. Because the degree of podocyte foot process effacement was felt to be more extensive than would be expected given the somewhat segmental and low-grade MN, the possibility of a superimposed podocytopathy (MCD) was raised. The time course of the worsening proteinuria was also felt to be incompatible with the relatively chronic stage of the MN. The constellation of biopsy findings raised the suspicion for an underlying allergic/drug-induced etiology. In light of this biopsy-proven diagnosis of MN, PLA2R [Anti Phospholipase A2 Receptor Antbiody] serology, anti-THSD7A [Anti Thrombospondin Type 1 Domain Contaning 7A Antibody], and anti-NELL [Anti Neural Epidermal Growth Factor-Like 1 Protein Antibody] were sent, and anti-PLA2R and anti-THSD7A came back negative. Anti-NELL was sent, but after discussion with the Mayo Clinic laboratory, it could not be performed due to a lack of current approval as a commercially approved assay. The patient had no signs of systemic lupus erythematosus, no indications of malignancy (on recent computed tomography (CT) imaging studies and colonoscopy), and no evidence of chronic infections or sarcoidosis to suggest any other etiologies for a secondary MN. Lyme IgG and IgM were sent to investigate Lyme nephritis and were not detected, as Lyme disease has been reported to cause a diverse spectrum of glomerular disease. Given the concern for a potential drug-induced MN, lack of serologic evidence for a primary form, and its low-grade chronic nature, immunosuppressants such as cyclophosphamide or rituximab were not pursued. The patient was further diuresed with metolazone 5 mg and furosemide 80 mg IV (intravenous) twice a day with improvements to his urine output and edema. Prednisone 10 mg daily was also started for his worsening SCr, which peaked at 5.6 mg/dL about 1 month after initial presentation. When the patient came to our clinic a month later, his symptoms had drastically improved. The patient lost around 24 pounds of water weight with noticeable improvements to his edema. Upon further investigation at that time, the patient finally recalled that he had been frequently taking ibuprofen 9 months prior to symptom manifestation. He was taking 400 mg of ibuprofen three to four times a day; he had no heavy metal exposure, industrial exposure, or new vaccines in the time prior to development of anasarca. He had been using over-the-counter ibuprofen at lower doses (once a day) nearly daily for his chronic knee pain for 10 months prior to his intensification of therapy years before stopping due to inefficacy and advice of nephrologists regarding NSAID nephrotoxicity. The findings suggesting NSAID-induced injury were tempered by finding of elevated urine copper levels. A 24-h urine panel for heavy metals showed undetectable levels of arsenic, zinc, cadmium, mercury, and lead. Copper levels were elevated at 27.1 microg/dL (upper limit of normal value 3.2 microg/dL) with a caveat that this is known to occur in high-grade proteinuria and with cirrhosis which the patient had. The patient also underwent workup for cirrhosis, including exclusion of Wilson's disease; the patient ceruloplasmin level was within normal limits at 27 mg/dL. Eye examination did not reveal Kayser Fleischer rings as well. The liver findings were attributed by hepatology to non-alcoholic fatty liver disease (NAFLD). Unfortunately, given the patient's financial status and insurance status, hair sampling for heavy metal toxicity was not financially viable or practical in this particular situation.

minimal change disease, acute interstitial nephritis, non-steroidal anti-inflammatory drugs, podocytopathy, secondary membranous glomerulonephritis

PMC5012809_01

Male

Cerebral tuberculomas are a rare and serious form of tuberculosis due to the haematogenous spread of Mycobacterium Tuberculosis. Symptoms and radiologic features are nonspecific, leading sometimes to misdiagnosis. We report the case of a 60-year-old male, with a history of diffuse bilateral infiltrative pulmonary disease at the stage of fibrosis, he made two generalized seizures associated with occipital headaches. CT scan showed a left frontal tumor, calcified lesion with edema around it. The patient was put under Depakine and corticosteroids. The evolution is marked by the occurrence of new seizures associated with heaviness of the right arm. Brain MRI showed a left posterior peripheral frontal meningioma with intralesional bleeding and significant edema around it with mass effect on the ipsilateral lateral ventricle. The patient was operated and the tumor was removed. In postoperative there was a Broca's aphasia with right hemiplegia. Pathological anatomical examination of the surgical specimen found a cerebromeningeal Granuloma with caseous necrosis in its pseudo tumor presentation (tuberculoma). The thoraco abdominal scan did not show any other tuberculosis lesions. The patient started antituberculosis treatment with 4 drugs (HRZE) for 2 months, followed by maintenance therapy (HR). The evolution was marked by the persistence of a right hemiplegia with Broca's aphasia. The patient was brought out in a wheelchair with functional rehabilitation sessions.

ct scan, cerebral tuberculoma, hemiplegia

PMC4309361_01

Male

The subject was a 51-year-old male. He was the driver of a car involved in a collision in which his car was hit from the left side and overturned. He was not wearing his seatbelt, and his left parietal region was the first area of impact. His car was overturned upside down, and he might receive injury with his own weight being as an external strength. On admission, his conscious level was JCS III-200, and he inflected the right elbow in response to pain stimulation. Since he was in shock and was experiencing respiratory failure, he was intubated and treated with a ventilator. We diagnosed his injury as Grade B according to the Frankel classification. An anteroposterior plain radiograph showed dilation of the left facet joint at the level of C5/6 and dislocation of the C5 vertebral body to the right side. A lateral plain radiograph showed interspinous dilation (Figure 2). We diagnosed a C5/6 fracture dislocation injury of LF Stage 2. Computed tomography (CT) revealed dilation of the C5/6 facet joint and fracture of the right lateral mass of C6 (Figure 3). We attempted manual reduction but failed. Therefore, while monitoring by X-ray, the loaded weight was gradually increased to be 10 kg; however only intervertebral dilation was observed, and reduction was not achieved. Further traction was considered to be dangerous, and immobilization in a halo vest was performed at the position where reduction could be performed. Due to deterioration of respiratory function, tracheotomy was performed approximately 1 month after the injury. We confirmed the patency of the vertebral and posterior communicating arteries by 3D CT angiography, and posterior fusion using a cervical spine pedicle screw was considered. However, we could not perform the procedure due to the patient's poor general condition. Approximately two months after the injury, we observed callus formation on plain radiographs and changed the halo vest to a Philadelphia collar. During the follow-up period, improvement of paralysis was not observed. He died of pneumonia at another hospital approximately 3 months after injury.

cervical spine, fracture dislocation injury, lateral flexion

PMC8551521_01

Female

A 44-year-old female with a history of incompletely treated latent TB was diagnosed with acute promyelocytic leukemia (APL). She was treated with arsenic trioxide plus all-trans retinoic acid. She also received dexamethasone for suspected pulmonary differentiation syndrome. Her initial treatment was complicated by neutropenic fever, hepatoxicity, and suspected acalculous cholecystitis. She later underwent a cholecystectomy tube replacement with subsequent tube removal. Approximately one month after her APL diagnosis, she was transferred to our facility for a higher level of care. Blood cultures obtained as part of evaluation for neutropenic fever were positive for Mycobacterium tuberculosis (TB); follow up respiratory cultures were also positive for TB. A bone marrow biopsy showed multiple granulomas. Computed tomography (CT) imaging of the chest/abdomen/pelvis demonstrated diffuse lymphadenopathy and a pericardial effusion. Due to abnormal liver function tests, a liver biopsy was performed and showed multiple foci of confluent coagulative necrosis. In addition to receiving empiric antimicrobials for neutropenic fever, initial TB treatment was adjusted for her liver disease and included rifampin (RIF), pyrazinamide (PZA), moxifloxacin (MFX), and ethambutol (EMB) (Fig. 1). Given concern for liver toxicity, PZA and MFX were changed to levofloxacin, amikacin and linezolid (LZD). When her liver enzymes improved, isoniazid (INH) and PZA were added, and levofloxacin was changed back to MFX. When her neutropenia resolved, she was discharged home on RIF, INH, PZA, EMB, LZD, and MFX despite persistent fevers which were attributed to widely disseminated TB with potential TB immune reconstitution inflammatory syndrome (IRIS). The blood isolate was sent to Reference Lab A for DST by agar proportion method and rapid molecular multi-drug resistant TB screen by line-probe assay. While the phenotypic DST results were pending, the line-probe assay showed no mutations in rpoB, katG, or inhA targeted regions, suggesting susceptibility to RIF and INH (Table 1). Therefore, moxifloxacin and linezolid were stopped. However, 10 days later, the phenotypic DST results returned and showed resistance to EMB and INH, but susceptibility to RIF and PZA. In the meantime, the patient was re-admitted to the hospital for persistent fevers and congestive heart failure, which improved with diuresis. Continued fevers were attributed to disseminated TB and TB IRIS. The persistent fevers, the need to resume APL treatment, and the drug resistance profile of the blood isolate prompted the treatment team to switch to a 5-drug regime: para-aminosalicylic acid (PAS), cycloserine, LZD, RIF and levofloxacin. The patient could not tolerate PAS which was then replaced by PZA and amikacin, leaving the regimen to include 6 drugs: PZA, RIF, cycloserine, LZD, levofloxacin, and amikacin. The respiratory isolate (1 month post admission) was sent to Reference Lab B and was susceptible to all first-line drugs as determined by liquid broth (MGIT) method. To investigate the discrepancy observed in DST results between the blood and sputum isolates, WGS was performed (Table 1). WGS revealed both isolates were of the Euro-American (LAM) lineage 4 and closely related to pan-drug sensitive TB CTRI-2 strain. Drug resistance prediction analysis using TB-profiler and ResFinder showed no known mutations to confer resistance to all first and second-line drugs (Table 1). Single nucleotide variant (SNV) analysis using CLC Genomics Workbench v12.0 (Qiagen, Germany) was performed using CTRI-2 (NCBI Reference Sequence: NC_017524.1) as the reference genome and showed only 5 SNVs between the blood and sputum isolate, confirming these two isolates are of the same lineage. Generally, the rate of change is 0.5 SNPs per genome per year and highly related isolates have within 5 SNPs differences. None of the 5 SNVs were within any drug resistance related genetic regions. The results of the WGS investigation were communicated to the California Department of Public Health (CDPH) TB Control team, who requested both isolates sent to the CDPH laboratory for confirmatory phenotypic DST and pyrosequencing. The results confirmed both isolates were susceptible to all first and second-line drugs, and no mutations were identified in the targeted regions for RIF and INH. At this point, 4 months had passed from the initial positive blood culture of TB, and treatment regime was reduced to 3 drugs: RIF, PZA, and levofloxacin for another 5 months. Patient successfully completed the treatment and achieved resolution of fever without the use of anti-inflammatory medications.

dst, drug resistance prediction, mycobacterium tuberculosis, whole genome sequencing

PMC6437980_01

Male

A 33-year-old patient was diagnosed in 2006 with stage IIIa nodular sclerosing Hodgkin lymphoma, treated with 12 different therapeutic regimens due to multiple relapses, including successively ABVD, radiotherapy, cisplatin containing regimen and autologous stem cell transplantation after BEAM conditioning regimen (year 4) (Additional file 1: Figure S1). He relapsed again, and was treated successively by bendamustin, FMS tyrosine kinase inhibitor, ICE, holoxan; bendamustin, and a first allogeneic stem cell transplantation from one of his HLA-matched sister (year 9) (conditioning regimen: Fludarabine 30 mg/m2 day 1-5; busulfan 3.2 mg/kg day 3 and 4; antithymocyte globulin 2.5 mg/kg day 5 and 6. 98% donor-type chimerism was achieved after this first allo-SCT. He unfortunately relapsed, and successively received vinblastine, navelbin, brentuximab, gemcitabine, and 8 injections of Nivolumab every 2 weeks (3 mg/kg; pre-approval access, French authorization), from March to June 2016 (year 10) followed by a second allogeneic SCT from another HLA-haplo-identical sibling donor (conditioning: TBI 2 Gy on day 1; Cyclophosphamide 14.5 mg/kg/day day 2 and 3; Fludarabine 30 mg/m2/day, day 2 to 6). Full chimerism was reached 1 month after the haplo-SCT. Clinical and radiographic resolution of cHL were reached, but in October 2016, he was hospitalized for an acute interstitial pneumonia associated with hepatic cytolysis and cutaneous eruption consisting of interspersed erythematous plaques with central vesiculo-bullous elements lacking Nikolsky's sign on trunk, shoulders, abdomen and legs. There were remaining patches of unaffected skin (Fig. 1). Mucosal (oral, ophthalmic and genital) lesions were also observed, with localized ulcerations and erosions. Bacteriological investigations including bronchoalveolar lavage were negative. Antibiotics were initiated but blood cultures returned negative. Subsequently, he presented with acute hypoventilation requiring invasive mechanical ventilation. Cerebral CT-scan and magnetic resonance imaging (MRI) were performed and did not reveal any cerebral abnormality. Lumbar puncture was performed, indicating normal white-cell count and protein/glucose levels. An electromyogram was performed, favoring myositis. Hepatic cytolysis and cholestasis progressed (maximal values: ASAT: 942 UI/lL, x 25.4 normal range; ALAT: 1 166 UI/L, x14.9 normal range; bilirubin 629 micromol/L, x37 normal range). Further complications occurred, including acute renal failure requiring hemodialysis, diarrhea and moderate colitis. Although some of these adverse events were compatible with severe GVHD, others were uncommon and highly evocative of immune checkpoint blockers-induced immune-related adverse events. The patient exhibited endocrine complications, with acute pancreatitis (Balthazar C) and hypothyroidism (TSH 59 IU/L). Moreover, troponin was elevated (4 microg/L) without any evidence of myocardial infarction; ECG (Fig. 2) showed regular rhythm at a rate of 55 bpm with normal QRS complex duration (< 0.12 s) and morphology. There were regular atrial waveforms seen at a rate of 70 bpm, and of same morphology with an isoelectric baseline between each atrial waveform. PP interval was constant with no relationship between the P waves and QRS, demonstrating atrioventricular dissociation. AS atrial rate was faster (70 bpm) than the ventricular rate (55 bpm). Complete heart block was diagnosed while subsequent junctional escape rhythm axis was normal at +45 (positive and equivalent QRS voltage in leads I and aVF). Beat to beat QRS complex amplitude remained constant along the trace, T wave amplitude and morphology as well (no electric alternans). There was no argument for left ventricular hypertrophy as RV2 + SV5 < 35 mm. Slope of ST segment was normal (no down or up-sloping ST segment depression). The QT/QTc intervals were normal (600 ms/428 ms). Additional transthoracic echocardiography confirmed an acute myocarditis. Eventually, these multisystemic injuries were hypothesized to result from cumulated immune-related adverse events induced by Nivolumab and/or exacerbated GVHD. The patient successively received mycophenolate mofetil, steroids (1 to 2 mg/kg) and polyvalent immunoglobulins, without any improvement leading to death. A skin biopsy was analyzed by HES coloration (Fig. 3a, b) after hospitalization, 3 months after the second allograft. The stratum corneum was thickened, the epidermis contained diffused inflammatory cells, and there was an epithelial intercellular oedema. Numerous inflammatory cells accumulated along the dermoepidermal junction, leading to its liquefaction. Necrotic keratinocytes were frequently seen, without typical satellite cell necrosis. One section stained with periodic acid Schiff (PAS) did not show any infectious agent (not shown). Immunohistochemistry revealed the presence of numerous CD3 + lymphocytes, with similar proportions of CD4 + and CD8 + lymphocytes (Fig. 3c-e). PD-L1 was found to be expressed in the inflamed dermoepidermal junction and in the epidermis both on immune cells and on keratinocytes (Fig. 3f, g). In the liver biopsy (collected 4 months after the second allograft) there was moderate inflammation, with discrete lymphocytic infiltration. An important cholestasis was seen, associated with foam cells. There was no vein endotheliitis. PD-L1 was found to be expressed on inflammatory cells, as well as on Kupffer and endothelial cells (Additional file 2: Figure S2). A muscular biopsy was performed 3 months after the haplo-SCT, and showed foci of endomysial inflammation (Fig. 4a, b). There was evidence of acute necrotizing myositis characterized by several foci of necrotic muscle fibers, macrophage activity and some regenerative fibers (Fig. 4b arrows highlight some basophilic fibers with nuclear internalizations). There was massive lymphoid-histiocytic infiltration of muscle fibers (Fig. 4b). The infiltrating cells were mostly CD3 + , although some CD68 + macrophages were present (Fig. 4e, f). In the endomysium, CD4 + lymphocytes were in higher density than CD8 + (Fig. 4g, h). There was a high expression of both HLA class I and HLA class II molecules at the surface of infiltrating cells and a diffuse sarcolemic expression. The expression of both HLA molecules was also sarcoplasmic in the inflammatory foci (Fig. 4c, d), confirming the diagnosis of myositis. PD-L1 was found to be expressed in the inflamed area, both on immune cells and myocytes (Fig. 4i-k).

allogeneic stem cell transplantation, gvhd, hodgkin lymphoma, immune-related adverse events, myositis, nivolumab, pd1

PMC5478571_01

Female

A 78-year-old woman with RA had been treated with infliximab (4 mg/kg) every 8 weeks for 3 years. After the initiation of infliximab, the RA activity was kept under control without remarkable complications. Eight weeks after the last dose of infliximab, she was admitted to our hospital because of a fever that had lasted for 6 weeks. Before the infliximab treatment was initiated, she had not received screening or treatment for a latent TB infection. Upon hospital admission, a laboratory investigation revealed elevated liver enzymes, aspartate aminotransferase of 208 IU/L, alanine aminotransferase of 148 IU/L, lactate dehydrogenase of 464 IU/L, and alkaline phosphatase (ALP) of 1,220 IU/L. Interferon-gamma (IFN-gamma) release assays (QuantiFERON(R)-TB Gold [QFT-G], Cellestis Limited, Carnegie, Victoria, Australia) were positive. A computed tomography (CT) scan showed chronic interstitial pneumonia in the chest (Fig. 1A) and gallstones and thickening of the gallbladder wall in the abdomen. She was diagnosed with cholecystitis and administered Piperacillin/Tazobactam. However, her fever did not fall, and her respiratory condition further deteriorated. On Day 6, she finally underwent tracheal intubation. An arterial blood gas analysis showed the partial pressure of arterial oxygen (PaO2) was 61 mmHg and the partial pressure of arterial carbon dioxide was 39 mmHg. The ventilator settings were set to pressure-control ventilation, a fraction of inspired oxygen (FiO2) of 0.5, pressure support of 3 cmH2O, and positive end-expiratory pressure of 11 cmH2O. Her PaO2/FiO2 (P/F ratio) was 122 mmHg, suggesting moderate ARDS according to the Berlin Definition. A chest CT scan showed bilateral, widespread, patchy, ill-defined lung opacification and interlobular septal thickening, but there were no clear miliary lesions (Fig. 1B). Because there was the possibility of acute exacerbation of interstitial pneumonia associated with RA triggered by infection, she underwent high-dose corticosteroid therapy and received an antimicrobial agent. Although her respiratory condition improved slightly, with the P/F ratio increasing to 171 mmHg, the fever did not come down. Because of her QFT-positive result on admission and the poor response to treatment thus far, we considered that she might have been suffering from miliary TB induced by infliximab. However, acid-fast staining of the sputum, bronchoalveolar lavage (BAL) fluid, urine, stool, and blood samples were all negative. Furthermore, a Mycobacterium tuberculosis polymerase chain reaction (TB-PCR) of a BAL fluid sample was also negative. The other differential diagnosis was malignant lymphoma, because the serum soluble interleukin-2 receptor (sIL-2R) level was very high (8,096 U/mL). A bone marrow biopsy of the anterior superior iliac spine was performed on Day 15 under mechanical ventilation, revealing epithelioid granulomas compatible with miliary TB. At that point, miliary lesions became apparent on a chest CT scan (Fig. 1C). TB was diagnosed based on the histopathological findings and clinical manifestation. Her P/F ratio increased to 305 mmHg, and the fever improved soon after she was administered anti-TB drugs on Day 18 (Fig. 2). Finally, an acid fast bacterial culture of the BAL fluid at intubation was positive for M. tuberculosis in a liquid culture on Day 24. She showed good progress because of the anti-TB treatment, but unfortunately, pneumothorax occurred before extubation. Although treatment with a chest drain was added, she died due to recurrent pneumothorax and a catheter-related blood stream infection. The clinical course, laboratory, and radiological findings are shown in Fig. 2. The findings of a pathological autopsy revealed diffuse alveolar damage (DAD), interstitial pneumonia, and innumerable granulomas in the lung, liver, bone marrow, spleen, and lymph nodes. Miliary nodules in the lung consisted of more unstructured granulomas. The DAD showed many hyaline membranes with severe inflammation and an increase in collagen fibers. There were numerous Langhans giant cells and epithelioid granulomas with substantial caseous necrosis in the lymph nodes. A few acid fast bacteria were observed in the lungs, lymph nodes, and liver. The details of the pathological findings are shown in Fig. 3.

acute respiratory distress syndrome, autopsy, immune reconstitution inflammatory syndrome, infliximab, rheumatoid arthritis, tuberculosis

PMC3949721_01

Female

An 18-year-old female Arab, a known asthmatic, presented to the emergency department of our hospital with complaints of chest pain and a nonproductive cough of 1-hour duration. She was conscious and well-oriented to the surroundings but had mild dyspnea. There was no history of receiving assisted mechanical ventilation. There was no previous history of pulmonary tuberculosis, recent trauma, surgery, or other intervention. Vital parameters were stable, and body temperature was normal. There was subcutaneous emphysema involving the right side of the neck. Auscultation of the chest did not reveal any significant abnormality. A chest radiograph was obtained, which revealed surgical emphysema along the upper part of the right lateral chest wall and the right side of the neck. Minimal pneumomediastinum was also noted with air within the superior mediastinum on the right. A loss of volume of the right lung was noted with a shift of mediastinum to the right and elevated right diaphragmatic dome (Figure 1). No lung consolidation, pneumothorax, or pleural collection was noted. The patient collapsed immediately after the chest radiograph was obtained. She was intubated and given intravenous fluids and vasopressors to control the hypotension. Her condition stabilized after 2 hours. The portable bedside chest radiograph revealed increased severity of pneumomediastinum, surgical emphysema, right lung collapse, and mediastinal shift to the right (Figure 2). Computed tomography (CT) imaging of the thorax was also performed, which confirmed the dissection of air into the mediastinal and subcutaneous spaces (Figure 3). A CT scan also revealed air within the posterior spinal extradural space in the thoracic spine (Figures 4 and 5), minimal pneumothorax on the right, and obstruction of the segmental right upper lobe bronchus by mucus plugs (Figure 6). She was hospitalized and treated with antibiotics, bronchodilators, oxygen inhalation, and other conservative measures. A bronchoscopic removal of mucus plugs and thick secretions was also performed. After only 5 days, clinical findings got better. The chest radiograph revealed resolution of the pneumomediastinum and surgical emphysema and a significant improvement of the right lung collapse and mediastinal shift to the right (Figure 7). She improved rapidly during her stay in the hospital and was discharged after 7 days.

asthma, pneumomediastinum, pneumorrhachis, pneumothorax, surgical emphysema

Axial nonenhanced chest CT scan. . Notes: This chest scan shows air dissecting through the mediastinal spaces (down arrow) and the subcutaneous soft tissue (up arrow). Minimal pneumothorax is also noted (left directional arrow). . Abbreviation: CT, computed tomography.

PMC8169262_01

Male

3-year 6-month-old male with genetically diagnosed type III osteogenesis imperfecta presented with left thigh pain after a child fell onto his leg. Radiographs obtained at that time demonstrated a minimally displaced left femur fracture about a proximally migrated 3.2 mm FDR. The patient was initially made nonweightbearing and treated with immobilization in a posterior slab splint. Prior to the injury described above, there was an anticipation of a revision surgery of the bilateral FDRs at approximately 4 years of age due to proximal migration of the left FDR with recurrent femoral deformity and right-sided FDR bending. Given the recent left femur fracture and right-sided rod deformity as shown in Figure 1, the decision was made to expedite the surgery prior to the right-sided rod requiring an osteotomy to revise. The patient underwent surgery at the age of 3 years and 8 months for revision of their bilateral Fassier-Duval rods. Regarding the left femur, the 3.2 mm FDR was successfully removed, a femoral osteotomy was performed to realign the femur, and a 4 mm FDR was successfully placed. Pertaining to the right femur, the female portion of the FDR was removed uneventfully followed by an unsuccessful attempt at removal of the male FDR. The male rod retriever shaft was placed over the male rod and tightened using the torque wrench. Following tightening, the male retriever was turned counterclockwise with a gentle pulling motion. At this point, the male retriever shaft fractured inside the femoral canal with the locking portion of the shaft still attached to the male rod as shown in Figure 2. Multiple unsuccessful attempts were made with different types of surgical instruments including micro and macropituitaries in an effort to engage the male retriever shaft fragment that was still attached to the male rod. Ultimately, a larger male retriever shaft (6.4 mm) was placed over the previously described shaft fragment and was able to be tightened around the fractured male retriever shaft to remove the fractured fragment and rod as one unit, as shown in Figure 3. Following the successful removal of the rod, a larger 4 mm FDR was placed in the appropriate position as shown in Figure 4. The patient had an uneventful postoperative course and was discharged from the hospital on postoperative day one.

PMC7191367_01

Male

A 33-year-old man was referred to our rheumatology department in 2003 because of low back pain accompanied by tenderness of the knees and small joints of the wrists. Since the axial pattern of affection dominated the clinical presentation at that time and the patient was HLA B27 positive, he was diagnosed with ankylosing spondylitis with accompanying peripheral arthritis. Low-dose glucocorticoids and methotrexate (15 mg weekly) were introduced, leading to significant improvement of signs and symptoms, as well as decline in the number of swollen and tender peripheral joints within the following months. Basal blood pressure values were normal (128/76 mmHg) while the estimated glomerular filtration rate (eGFR) was 99.8 mL/min/1.73 m2. Despite initial improvement, the following time course was marked by aggravation of signs and symptoms consistent with peripheral polyarthritis, leading to a diagnosis of seronegative RA in 2005, fulfilling the 1987 classification criteria. Methotrexate was continued, now in combination with sulfasalazine (2 grams daily) being replaced with leflunomide (20 mg daily) after several months. Despite combined treatment with conventional disease-modifying agents (DMARDs) and concomitant use of low-dose glucocorticoids, the patient suffered from a persistently active disease with a 28-joint disease activity score calculated using the erythrocyte sedimentation rate, ESR (DAS28-ESR) of 5.52. This prompted the initiation of adalimumab (40 mg subcutaneous every other week), while methotrexate was continued at a lower dose (10 mg weekly). This treatment strategy led to a satisfactory clinical response and reduction of DAS28-ESR to 2.66. In 2006, the patient developed a psoriatic rash of the palms and soles, which was successfully treated with topical therapy. In the same year, the patient developed arterial hypertension (175/94 mmHg), for which an ACE inhibitor was introduced. In 2011, the patient was still in stabile remission of his rheumatic condition (s) while continuously taking the biological drug; however, routine urinalysis unexpectedly revealed microscopic hematuria (urine sediment E 20-30 erythrocytes and 66-73% dysmorphic erythrocytes), accompanied by non-nephrotic proteinuria (2.25 g in daily urine, dU) with eGFR of 56 mL/min/1.73 m2. Urine cytology revealed no urothelial atypia, and urine was negative for M. tuberculosis. The erythrocyte sedimentation rate (ESR) was increased (64 mm/h) as well as the C-reactive protein (CRP) level (18.3 mg/L). The complete blood count was unremarkable, as well as blood urea nitrogen (BUN) (5.0 mg/dl) and serum electrolytes. Serum creatinine was increased (137 mumol/l), as well as total cholesterol (5.7 mmol/L), LDL-cholesterol (3.52 mmol/L), and triglycerides (2.78 mmol/L). Antinuclear, anti-neutrophil cytoplasmic, and anti-glomerular basement membrane antibodies (ANA, ANCA, and GBM, respectively) were negative. Serum protein electrophoresis, immunoelectrophoresis, and immunofixation were normal as well as serum complement levels (C3 and C4). Screening for hepatitis B, hepatitis C, and HIV (human immunodeficiency virus) were negative. On ultrasonography, both kidneys were of normal size with hyperechogenic parenchyma. Percutaneous kidney biopsy was performed, and its results are shown in Figures 1(a) and 1(b). On light microscopy, diffuse mesangial hypercellularity was observed in all glomeruli, whereas global sclerosis was established in 1 of 15 glomeruli (6.66%). The tubules demonstrated degenerative changes while there were no changes on arteries. A moderate mononuclear infiltrate and mild fibrosis was noted in the interstitium. Immunofluorescence microscopy revealed mild mesangioproliferative changes. Electronic microscopy showed eosinophil infiltrates mostly in the mesangium, while several subendothelial and subepithelial eosinophil deposits were seen in the capillaries. In some glomeruli, there were signs of podocyte loss. Electronic microscopy also revealed glomerulonephritis with diffuse mesangial deposits and several subendothelial and subepithelial deposits compliant with glomerulonephritis caused by circulating immune complexes. The findings were in concert with the diagnosis of IgAN. There were no elements of diabetic nephropathy. The patient's MEST-C score was M1, E0, S1, T2, and C0. Treatment with adalimumab and medium-dose glucocorticoids (prednisone 20 mg) was continued as well as an ACE inhibitor. Over the next two years, the patient was in a state of low disease activity (DAS28 3.08) of his RA, with progression of chronic kidney disease (eGFR 35.3 mL/min/1.73 m2) and persistent proteinuria (2.26 g/dU). This prompted discontinuation of adalimumab and a further increase in the dose of glucocorticoids (prednisone 60 mg), with the intention to control the renal disease. Due to the increased prednisone dose, the patient gradually developed cushingoid features including type 2 diabetes mellitus; he was diagnosed in 2014. A slight improvement in kidney function (eGFR 44.1 mL/min/1.73 m2) and proteinuria (1.60 g/dU) allowed for a reduction of the prednisone dose to 40 mg. Of note, the patient's blood pressure was unremarkable, often being 120/80 mmHg or even less. In 2015, the patient's kidney function was without further deterioration (eGFR 42.2 mL/min/1.73 m2) and without progression of proteinuria. Diabetes was not adequately controlled, and the patient also experienced a relapse of his RA; so, rituximab was introduced in 2016. Unfortunately, the drug had to be discontinued after three cycles due to lacking efficacy and an increase in proteinuria from 0.78 to 2.04 g/dU. After discontinuation of rituximab, a decision was made to commence treatment with baricitinib, an oral selective JAK inhibitor. This finally led to the achievement of a low disease activity state of RA. However, the patient still continued to have persistent proteinuria of 1.9 g/dU, with no further decline in the eGFR.

PMC2834956_01

Female

A 35-year-old woman of African descent with chronic alcohol and nicotine abuse was admitted to our hospital in November 2007 with a two-day history of lower left-sided abdominal pain as well as febrile temperatures of 38.8 C and elevated inflammation parameters. Her past medical history included HIV infection that was first diagnosed in 2001 and treated with a combination of lamivudin 150 mg plus zidovudin 300 mg (Combivir) and efavirenz 50 mg/200 mg (Sustiva). In that same year, the patient underwent surgery (a longitudinal incision laparotomy) for an ovarian cyst. The patient did not tolerate antiretroviral treatment (due to side effects) and stopped taking her HIV medication in 2006, one year prior to her current admission. In November 2007, the viral load was 59.000 copies/mL and CD4 count was 13% or 159 cells/muL. As a secondary finding, a chronic hepatitis B infection with a low viral load was detected during this hospitalization, whereas a hepatitis C infection was excluded. A prior history of tuberculosis was denied by the patient. On ultrasound examination a 5 x 6 cm cystic mass lesion in the area of the left adnexa could be displayed (Figure 1). Several surgical procedures including laparoscopy with subsequent drainage, laparotomy, exstirpation of the cyst, and one-sided ovarectomy were discussed with the patient. First, a diagnostic laparoscopy was performed, revealing several intraabdominal adhesions of the intestine as well as a severe pus-filled abdominal cavity. Therefore, a median longitudinal laparotomy had to be performed. After taking microbial samples, abdominal adhesions were divided and extensively rinsed. Afterwards, a tubectomy on the left side was performed and a drainage system was inserted. Following the operation, an intravenous antibiotic therapy with ciprofloxacin and metronidazol was started and the pelvis minor was rinsed twice daily. Afterwards, the patient recovered quickly from the surgical intervention. Ten days later, the patient was discharged from the hospital in a good general state of health. Due to the known HIV-infection, detailed analysis of pus obtained during the operation was necessary. In spite of this, cultures for aerobic and anaerobic microbes, cultures of Mycobacterium tuberculosis, as well as Chlamydia trachomatis and Chlamydia pneumoniae were negative. Histopathological studies showed a granulomatous salpingitis with central necrosis of the left fallopian tube (Figure 2) and subsequent PCR demonstrated evidence for M. Tb-complex specific PCR products. Special stains (Ziehl-Neels en and Auramin) for acid-fast organisms remained negative. Interestingly, chest X-ray analysis performed days after the surgical procedure did not demonstrate any signs of tuberculous involvement of the lung. Because of her underlying HIV disease, the patient was referred to our infectious diseases unit and was treated according to current recommendations with a standardized short-course chemotherapeutic regimen of isoniazid/vitamin B and rifampicin for 6 months and pyrazinamid and ethambutol for 2 months. Due to her low CD4 counts (170 cells/muL = 12%) prophylactic antibiotic therapy with cotrimoxazole was initiated (this has been shown to decrease mortality in HIV/TB- coinfected patients). She responded promptly to antibiotic therapy as evidenced by declining liver enzymes and CRP after two, three, and seven weeks, respectively. Her WBC remained constant within commonly accepted limits. Initiation of an antiretroviral treatment (ART) against HIV was to be started at a later time point (between 2 weeks and 2 months later) in order to not interfere with tuberculosis regimens.

PMC4992205_01

Unknown

Four piglets, 3-4-days old, that had died during an outbreak of high morbidity, low mortality, neonatal diarrhoea in a 1000 sow commercial pig herd were submitted for necropsy. Details of treatment prior to death were not available. At gross necropsy all four carcasses were well preserved with adequate body fat reserves. Stomachs were filled with milk. There was mild mesocolonic oedema, and small intestinal and colonic contents were soft and yellow in all four. No gross changes were noted in intestinal, caecal or colonic mucosa. Other body systems were unremarkable. At least 6 sections from representative areas along the length of the small intestine, a section of caecum and at least six sections of spiral colon were sampled for histopathology. They were fixed in buffered formalin, processed routinely and stained with haematoxylin and eosin. On histopathological examination three of the piglets had mild (n = 1) to severe (n = 2), multifocal, superficial fibrinosuppurative and erosive colitis with neutrophils and fibrin spilling from lamina propria through the eroded epithelium and into the lumen ('volcano lesions') (Fig. 1). In the other piglet there was a mild, multifocal, suppurative mesocolitis. In addition, in two of the piglets there was acute, mild, superficial, suppurative enteritis, with superficial necrosis and microthrombosis in one of the piglets. All four piglets also had mild atrophic enteritis. Colonic contents were positive for C. difficile toxins A/B using using Premier Elisa Kit Toxins A&B (Meridian Bioscience Inc.) Fifteen muL colonic contents were treated with 50 muL (96 %) ethanol. Fifteen muL of each mixture was transferred individually to plates containing Brazier's cefoxitin cycloserine egg-yolk (CCEY) medium (Lister, 2014). Plates were incubated anaerobically (10%H2, 10%CO2 and 80%N2) at 34 C for 48 h. 'Broken glass' colonies, typical of C. difficile, were transferred to blood agar plates and incubated for a further 48 h. Chelex-100 chelating resin was used for whole-cell DNA extraction of the resulting colonies. PCR-amplification of the DNA was performed with BioMix Red mastermix (Bioline) and CD-16s primers, 5'-CTG GGG TGA AGT CGT AAC AAG G-3', 6'-GCG CCC TTT GTA GCT TGA CC-3' (Eurofins MWG). PCR products were transferred to a heating block, set to 75 C, for 45 min to concentrate products to c.20 muL, before electrophoresis on a 3 % agarose gel with GelGreen nucleic acid stain (Biotium). The gel was placed under ultraviolet light in a closed chamber of Bio-Rad Universal Hood II. Results were visualised with Bio-Rad Quantity One (4-6-1) 1-dimensional analysis software. PCR ribotypes were successfully obtained for three piglets; two were ribotype 078 and one was ribotype 110. The fourth piglet's sample failed to yield a pure culture after treatment with 96 % ethanol and anaerobic incubation with CCEY medium. Clostridium perfringens (C. perfringens) was isolated by direct anaerobic culture of intestinal contents using pre-reduced 5 % Columbia sheep blood agar (SBA) and fastidious anaerobe blood agar with nheomycin (E&O Laboratories, Scotland). C. perfringens alpha toxin was detected in a pooled sample of small intestinal contents using a sandwich ELISA, testing for alpha (alpha), beta (beta), epsilon (e) toxins and C. perfringens Antigen (BioX Diagnostics, Belgium). Rotavirus group B was detected in small intestinal contents in two of the piglets using modified versions of previously described PCR methods. PCRs for porcine coronaviruses and porcine reproductive and respiratory virus were negative using modified versions of previously described methods. No antigen was detected using anti-Cryptosporidium parvum monoclonal antibody labelled with fluorescein isothiocyanate (Bio-X Diagnostics, Belgium, Catalogue Number BIO 073).

clostridium difficile, pcr ribotyping, pigs, typhlocolitis

PMC7145159_01

Male

A 65-year-old man with a history of peptic ulcer disease status postremote Billroth II gastrojejunostomy in 1970 with known metastatic gastric carcinoma presented in the outpatient setting with several months of abdominal pain, fatigue, weight loss, and poor appetite. His body mass index was 15 kg/m2. This constellation of symptoms resulted in interruption of his chemotherapy regimen. On examination, his abdomen was soft and initially nondistended. He had hyperactive bowel sounds, normal pitch. There was moderate tenderness to palpation over the right upper quadrant and left side, no rebound, and no guarding. The laboratory results revealed anemia hemoglobin 7.7 g/dL, alanine aminotransferase 43 U/L, aspartate aminotransferase 45 U/L, alkaline phosphatase 2006 U/L, TBili 0.5 mg/dL, and albumin 2.5 g/dL. He was admitted to the hospital for management. Abdominal computed tomography showed Billroth II gastrojejunostomy with high-grade afferent loop obstruction due to enlarging gastric mass with probable extragastric extension into the left upper quadrant and decompressed distal bowel. There was contact without definite invasion of the pancreatic tail and lateral limb of the left adrenal gland. Interval increase in biliary ductal dilatation, worst in the left hepatic lobe with concomitant gallbladder, and pancreatic duct distension were noted all consistent with downstream obstruction (Figure 1). Given his body mass index of 15 and notable deconditioning, he was deemed a priori not to be a surgical candidate for a palliative bypass. Upper endoscopy showed a circumferential, fungating, and ulcerated friable 4-5 cm mass of malignant appearance involving the anastomosis. The mass caused near-total obstruction of both the pancreatobiliary and efferent limbs (Figure 2). Because of the severity of his obstruction, a pediatric gastroscope was required to pass the tumor. A guidewire was passed into the afferent limb through the pediatric gastroscope after which a second guidewire was passed into the efferent limb (Figure 3). The guidewires were both passed before any stent deployment, given a concern for possible worsening obstruction after the first stent was placed and expanded. The afferent limb guidewire was backloaded through a duodenal stent loaded in a therapeutic gastroscope, and the gastroscope was advanced through the wire. An uncovered metal stent was deployed across the gastric mass into the afferent limb under endoscopic and fluoroscopic guidance. The efferent limb guidewire was then backloaded through a second duodenal stent loaded in the therapeutic gastroscope, and the gastroscope was advanced over the wire. A second uncovered metal stent was deployed across the gastric mass into the efferent limb under endoscopic and fluoroscopic guidance (Figure 4). The afferent limb was deployed first because there was concern that the first stent would obstruct the lumen and ability to place the second stent. In addition, afferent limb obstruction was the most acute pathology, as evident by this patient's presenting symptoms, laboratory tests, and imaging. Using the double guidewire technique was critical in ensuring our ability to properly deploy the second stent. Without a double wire technique, given the degree of obstruction, it would likely not have been possible to introduce a wire down the efferent limb after afferent limb stent deployment. To prevent stent migration, a "kissing-stents" technique was used, and 2 clips were deployed to attach the gastric end of both metal stents (Figure 5). The patient returned to the floor. After the procedure, he was able to resume a clear liquid diet the first day, followed by a duodenal stent diet. Liver function tests normalized except for alkaline phosphatase, which continued to downtrend slowly ( Table 1). Stents remain patent because of the time of this report, and he was tolerating oral intake.

PMC4683789_01

Male

A 50-year-old male presented to the Cardiology department due to edema of the legs, erythema, pain, abdominal swelling, and was hospitalized with pulmonary hypertension, right heart failure, atrial fibrillation, chronic obstructive pulmonary disease, and cellulitis. The patient had a history of appendectomy when he was 20 years old and had been stabbed in the abdomen when he was 35 years old. He had been stabbed twice, and 1 h after the stabbing, he had been successfully treated by general surgery. The patient had been discharged 1 week postoperatively. The patient also had a 4-year history of smoking during his adolescent period. Five years earlier, the patient (age 45 years) had presented to the Cardiology outpatient service and was diagnosed with New York Heart Association (NYHA) Class II shortness of breath. On echocardiography (echo), his right heart cavity dimensions were mildly increased and pulmonary artery systolic pressure was found to be 45 mmHg. After treatment, his complaints regressed completely. Three years earlier (age 47 years), he had been admitted to the Pulmonology department with abdominal and bilateral leg swelling, and shortness of breath (NYHA Class III) complaints. CT thorax was performed and he was diagnosed with right heart failure. But dilated IVC was missed or might have been accepted as secondary dilatation to pulmonary hypertension and right heart failure. Intravenous diuretics, steroids, teophylline, and inhaled bronchodilator treatment had been administered. Subsequently, his complaints regressed. His echo findings at that period of time were as follows: Left ventricular ejection fraction 65%, Grade I diastolic dysfunction, normal left heart cavities, significantly enlarged right heart cavities, pulmonary artery systolic pressure 70 mmHg, and Grade 2-3 tricuspid failure. He was being closely monitored by the pulmonologist for pulmonary hypertension. One year earlier (age 49 years), he had been admitted to the Pulmonology department due to newly developed high ventricular rate atrial fibrillation (168 bpm) resulting in significant abdominal ascites, diffuse edema of the lower extremities, and crackles in the middle and lower lung zones (NYHA functional Class IV). At that period of time, the echo had shown normal left heart cavity dimensions, left ventricular ejection fraction 50%, paradoxical interventricular septal motion, significantly enlarged right heart cavities, pulmonary artery systolic pressure 95 mmHg, and Grade 3 tricuspid insufficiency. The patient was started on digoxin 1 x 1 tb, diltiazem 2 x 120 mg, and warfarin by the cardiologist. In 1 week, his symptoms regressed to NYHA Class III and he was discharged from the hospital. Fifteen days later, the patient was admitted to Emergency department with symptoms of worsening right heart failure and shortness of breath; therefore, he was moved to the Cardiology department and started on intravenous furosemide, spironolactone 25 mg, clexane 2 x 0.6 cc (because of subtherapeutic international normalized ratio), and continued on diltiazem and digoxin. According to the dermatologist's recommendation, he was also started on ampicillin/sulbactam 4 x 1 g IV. Laboratory findings were as follows: Blood urea nitrogen 60 mg/dl (normal range 7-22 mg/dl), creatinine 1.2 mg/dl (normal range 0.8-1.3 mg/dl), aspartate aminotransferase 40 U/l (normal range 0-35 U/l), alanine aminotransferase 45 U/l (normal range 0 -35 U/l), hemoglobin 12.8 g/dl (14.0-17.4 g/dl), white blood cells 14,500/microl (normal range 3,500-10,500 microl). On the second day of admission, the patient first developed respiratory arrest and then cardiac arrest. Cardiopulmonary resuscitation (CPR) was initiated, the patient was intubated, and on the 5th minute of CPR, he gained basal rhythm of atrial fibrillation and a blood pressure of 100/60 mmHg. The patient was then transferred to the intensive care unit and placed on a mechanic ventilator. With an initial diagnosis of pulmonary embolism, the patient had undergone pulmonary CT angiography; however, no thrombi were detected. Deep vein thrombosis (DVT) protocol CT was not performed. Only thorax CT angiography and lower extremity venous Doppler ultrasonography were performed. But no thrombotic formation was detected at Doppler examination. The diagnosis was missed by physicians. But simple abdominal auscultation revealed the diagnosis. The IVC diameter was found to be 19 cm. On cardiologic evaluation, at the tricuspid focus, on the left and right corners, a harsh pansystolic murmur at 4-5/6 intensity was heard. The liver was palpable 7-8 cm under the costal arch, and diffuse ascites was detected in the abdomen. Edema of the legs was 3+. On the umbilical region of the abdomen, a continuous thrill and a machine-like murmur were detected [Figure 1]. On echo, right cardiac cavities were severely enlarged, and 3-4 degree of tricuspid failure, pulmonary artery pressure of 75-80 mmHg, and normal left heart cavities were detected. IVC was measured and found to be 18 cm. On the region of abdominal murmur, the echo probe showed fistula between the abdominal aorta and the IVC on transverse plane [Figure 2a and b]. Transesophageal echocardiography showed intact interventricular septum and patent foramen ovale of the interatrial septum. Right to left shunt of the patent foramen ovale was seen. CT angiography was performed in order to confirm the ACP and to determine its dimensions. Right at the lower level of renal artery and bifurcation of the aorta, between IVC and abdominal aorta, a fistula was detected. At the localization of fistula on the lower level of the renal artery [Figure 3a], the diameter of the aorta was 22 mm, IVC diameter was 99 mm, and the diameter of the fistula tract was 11 mm. At the localization of fistula on the abdominal aortic bifurcation [Figure 3b], the aortic diameter was 25 mm, IVC diameter was 169 mm, and fistula tract diameter was 17 mm. Hemodynamic work-up and shunt measurements were planned. On abdominal aortography, findings consistent with CT angiography (two fistulas from the abdominal aorta to the IVC) were found [Figure 4]. Oxymetrically calculated left-to-right shunt was 2.8. On coronary angiography, the coronary arteries were normal and systolic pulmonary artery pressure was 75 mmHg [Figure 5]. The patient's condition was hemodynamically stabile; however, considering the possible complications, the ACP was decided to be closed percutaneously. The procedure was to be performed after the pneumonia secondary to intubation had resolved. Despite the antibiotic therapy, the pneumonia did not resolve. The patient developed sepsis and died of septic shock in the intensive care unit.

chronic aortocaval fistula, computed tomography, penetrating abdominal trauma

PMC9845722_01

Male

A nine-month-old boy chiefly complained of vomiting and mental fatigue; these symptoms were reported to have lasted for half a day by the parents. The patient presented the following recent illness history: the day before admission, the child vomited stomach contents twice without obvious triggers and subsequently experienced mental fatigue and hypoglycemia. After half a day of outpatient treatment, the child remained mentally fatigued, with a poor response and reduced appetite. His parents denied any dietary complications. The patient was transferred to our hospital for further diagnosis and treatment. Since disease onset, the patient had experienced mental fatigue, decreased appetite, and poor sleep, although no significant change was observed in body weight. The patient's health and personal history were as follows: Birth history: G2P2, full-term vaginal delivery; birth weight 3.85 kg. (2) Newborn disease screening history: An newborn screening sample obtained on the third day after birth was reported to be elevations of C0, C6, C8, C10, C12, C14:1, and C14:2. (3) Feeding history: Breastfed for four months and post-formula fed until admission, with the gradual addition of complementary food from six months of age with no adverse reactions. (4) Growth and developmental history: Weight and height gradually increased, with laughing at two months, stable neck erection at three months, and turning over at five months; however, unstable neck erection was observed after admission at nine months. (5) Family history: Healthy parents and non-consanguineous marriages, although the patient's sibling exhibited abnormal screening results, poor overall health, and a low height and weight and was prone to colds. Physical examination showed that the body weight was 9.0 kg; height was 72 cm; the limbs were hypotonia; the patient's neck erection was unstable. He was unable to sit alone because the lower limbs could not support his body weight in the standing position. However, bilateral knee tendon and bilateral Achilles tendon reflexes were elicited symmetrically. No abnormal touch was found, physiological reflexes were present, and Bruchner's, Klinefelter's, and double Barthel's signs were all negative. The preliminary diagnosis was a suspected genetic metabolic disease. Auxiliary examination revealed the following: (1) Color Doppler ultrasound: Hepatomegaly, 5.0 cm below the right rib, liver parenchyma echo enhancement; (2) blood routine test: WBC, 27.1 x 10*9/l; (3) biochemical examination: HCO3-, 14.2 mmol/L; TBA, 51.6 micromol/L; ALT, 110 U/L; AST, 250 U/L; GLU, 2.90 mmol/L; UA, 550 micromol/L; LDH, 429 U/L; and CK, 222 U/L; (4) urine organic acids: Glutaric acid, 2-hydroxyglutaric acid, 3-hydroxyglutaric acid, and other glutaric acid increased; (5) blood mass spectrometry screening: C0, C6, C8, C10, C12, C14:1, and C14:2 increased; (6) the remainder of the examinations, such as brain MRI and ECG, were all normal, as shown in Table 1. To confirm the diagnosis, peripheral blood samples were collected from the proband for WES. After hospitalization, ceftazidime anti-infection, glutathione liver protection, and other treatments were all administered. According to the children's blood tandem mass spectrometry and urine organic acid results, late-onset MADD was considered a possibility, and in response, the patient was given large doses of vitamin B2 (50 mg, tid), levocarnitine (10 ml, oral tid), coenzyme Q10 (50 mg, tid). After 1 week, WES results confirmed our diagnosis. At the time of discharge, the patient appeared responsive and exhibited normative behavior for his age. However, the liver reached 3 cm below the ribs, and low muscle tone was observed in the limbs. Furthermore, unstable neck erection continued; the patient could not raise his head in the prone position, support the elbow, sit unsupported, and support the weight of the lower limbs in the standing position. Prescription of the doctor during discharge: Levocarnitine 3.33 ml, oral tid; vitamin B2 50 mg, tid; coenzyme Q10 50 mg, tid; compound glycyrrhizin half tablet tid; low-fat, low-protein, high-carbohydrate diet. Blood mass spectrometry and urinary organic acids were rechecked one week after hospitalization: C6, C8, C10, C10:1, C12, C14:1, and C14:2 all increased. Meanwhile, urinary organic acid results were normal. After follow-up at six months, physical examination showed that body weight was 10.4 kg and height is 79 cm. He can sit alone, hold his head up, turn over, crawl, pronounce babamama, and walk a few steps alone. Muscle strength and muscle tone of the limbs were normal, physiological reflexes existed, and pathological signs were all negative. Auxiliary examination revealed C6, C8, C10, C10:1, C12, C14:1, and C14:2 all increased, however, urinary organic acids results remained normal. After a subsequent follow-up at one year, physical examination showed that the weight was 11 kg, height was 88 cm, and he can walk alone and express simply. Blood tandem mass spectrometry showed that C6, C8, C10, C10:1, C12, C14:1, and C14:2 still increased.

etfdh, c1842_1845dup, multiple acyl-coa dehydrogenase deficiency, mutation, novel

PMC9513355_01

Female

A 27-year-old woman with a history of IVF-ET 7 months ago was treated with glucocorticoid, namely, 10 mg of prednisone per day for 30 consecutive days before implantation, and spontaneous abortion occurred after 4 months of pregnancy. She was previously healthy and denied any previous history of TB and close family contacts. Several days later, symptoms such as headache, vomiting, and intermittent low-grade fever developed, and she received several symptomatic treatments in the first month without any effect. Therefore, she was admitted to the neurology department at the local hospital. Figures 1A,B show multiple lesions on her brain's magnetic resonance imaging (MRI). Chest radiography was normal, and the results of a human immunodeficiency virus (HIV) test was negative. In the absence of definite etiological evidence, empirical anti-TB drugs, including isoniazid, rifampin, ethambutol, and pyrazinamide, as well as some symptomatic treatments, were given. The patient was later transferred to the First Affiliated Hospital of Zhengzhou University after her condition worsened with paroxysmal coma and seizures. The signs of meningeal irritation were positive. Lumbar puncture showed the intracranial pressure exceeding 400 mmH2O. CSF examination revealed low glucose (30-40 mg/dl), low chloride (119 mmol/L), WBC of 290*10 9/L (65% lymphocytes and 27% neutrophils), and extremely high level of protein (297.5 mg/dl). Additionally, purified protein derivative (PPD)-positive cells accounted for 24% (reference value: <13.5%) and early secretory antigenic target (ESAT)-6 positive cells represented 23% (reference value: <9.5%) in the CSF. No mycobacteria were found in the CSF by stained smear and culture. Electroencephalogram (EEG) displayed paroxysmal spikes or sharp slow waves. No loss of consciousness with seizures occurred under the continuous administration of the previous anti-tuberculous therapy (ATT) combined with levofloxacin, prednisone, and partial symptomatic treatment, but her headache and intermittent fever were not relieved. Worse still, the patient developed herniation at the end of the first week of treatment, and she received continuous lumbar cerebrospinal fluid (CSF) drainage for one week. Based on routine treatment, intrathecal injections of isoniazid, dexamethasone, and chymotrypsin were performed every two days after removing the drainage tube. After another two months of treatment, the symptoms of fever, headache, and epilepsy were significantly relieved. The improvement of brain MRI is shown in Figure 1C. Her intracranial pressure decreased to 190 mmH20. CSF examination showed reduced WBC of 30*10 9/L (79% lymphocytes), significantly decreased protein (99.5 mg/dl), and normal glucose and chloride.

anti-tuberculosis therapy, embryo transfer, in vitro fertilization, intrathecal injection, multiple brain tuberculoma, tuberculous meningitis

PMC9513355_02

Female

A 27-year-old woman with a history of IVF-ET six months ago received 10 mg of prednisone per day for 20 days before embryo transfer. She suffered from spontaneous abortion one month ago and had a high fever immediately after the abortion. She was previously healthy and denied any previous history of TB and close family contacts. She was diagnosed with interstitial pneumonia and cured at a local hospital. Two weeks after the cure, she suddenly suffered from headaches, vomiting, and insanity. The signs of meningeal irritation were positive. In terms of auxiliary examination, CT showed no lung abnormalities, while brain MRI revealed multiple lesions (Figure 2A). The result of the HIV test was negative. The lumbar puncture showed an intracranial pressure of 110 mmH2O. Examination of CSF demonstrated a low level of glucose (40-50 mmol/L), pleocytosis (WBC was 22*10 9/L with 73% lymphocytes), and a high level of protein (121.2 mg/dl). Moreover, PPD-positive cells accounted for 26%, and ESAT-6 positive cells represented 25% of the CSF. No mycobacteria were found in the CSF by stained smear and culture. After 1 month of anti-tuberculous drugs (isoniazid, rifampicin, ethambutol, and pyrazinamide), levofloxacin, and some symptomatic treatment, the patient still had severe headaches and vomiting. Brain MRI showed no significant changes compared with the previous scan (Figure 2B). Intrathecal injections of isoniazid, dexamethasone, and chymotrypsin were performed to specifically prevent anti-TB and reduce arachnoid adhesion. Combined with the previous therapy for another month, her clinical symptoms were relieved. Moreover, the size and number of lesions were significantly reduced on brain MRI (Figure 2C).

anti-tuberculosis therapy, embryo transfer, in vitro fertilization, intrathecal injection, multiple brain tuberculoma, tuberculous meningitis

PMC9376603_01

Male

What follows is a report by the first author of a 55 year old US Army veteran who had been diagnosed by the VA with combat related PTSD. His background included having graduated from the US Military Academy at West Point, the American army's premier training school for officers. After 10 years of active duty in various non-combat assignments, he left active service for law school. While building a career in law over the next 20 years, he remained active in the US Army Reserve and National Guard. In 1990 during Operation Desert Storm his National Guard Military Police Unit was deployed to Saudi Arabia to handle Iraqi prisoners of war. His unit was again called up for active duty during the Balkan wars in 1995, this time for base security of NATO installations. Since neither of these two active-duty assignments had any combat components, he returned each time physically and mentally in good shape. Due to his unique background in the law and training skills, he was recalled with rank of Colonel to active duty in 2008. He was tasked to command a Task Force to train Afghan Police units to be law enforcement officers in rural Kandahar Province. This was the most contested part of Afghanistan and the twelve 15-man training teams, and their trainees often came under fire. In contrast to combat units in the area, his teams had not had casualties for the first 11 months of their 1-year tour of duty. Indeed, the men in his task force came to believe that they were in a divine protective bubble. Then just 2 weeks away from the end of their tour in Afghanistan "the shit hit the fan" (his words), and two of his men lost their lives while five more were seriously wounded. He felt responsible for their deaths and berated himself for exposing them to danger "needlessly" before their scheduled return home. In what is known as survivor guilt (Kubany et al.,), he felt he should have been killed instead of the men. He felt especially guilty about the death of one his most valuable non-commissioned officers, who drowned when his Humvee ran off the road during a night mission and overturned in an irrigation canal. He said that initially he had tried to "sort things out" by himself for a year, thinking that with time he would get better. When his symptoms persisted, and he feared that his wife would leave him, he signed up for standard care with the two nearest Veterans Administration (VA) centers. He was promptly diagnosed with PTSD and comorbid depression and anxiety. He went to weekly individual counseling, and twice weekly support group meetings with fellow veterans with PTSD. He was also prescribed a handful of medications for depression, anxiety, ADHD, and sleep. After 2 years, and seeing little improvement in his PTSD symptoms, he embarked on an online search for alternatives. He came upon Neurofeedback as a remedy for PTSD and found that I was the only VA-accredited therapist providing this intervention in West Virginia. Because the VA was not offering this therapy in-house, he applied for a referral to me through the Community-Based Care program. After getting VA approval we began Neurofeedback training on May 25, 2012. On intake, he filled out the PCL-5, the standard instrument used by the US military to assess PTSD. His score was 71, which falls into the category of moderate to serious. To further assess his PTSD as well as other issues, he also filled out the 150 item Symptom Rating Scale3. The high-rated symptoms relating to PTSD were "nightmares, flashbacks, anxiety attacks, sleeplessness, migraines, angry outbursts, problems with focusing at work, depression, and lack of connectedness." In addition, he listed "numbing, problems of relations with coworkers and his wife, and pretty much everything." Evidence of his determination to recover was that he committed himself to 10 Neurofeedback sessions in 5 weeks. Although working full time as Assistant Prosecuting Attorney, he faithfully made the 3-h roundtrip twice weekly and attended all 10 sessions. Each session was about 50 min long and consisted of debriefing on inter-session progress by reviewing the identified major symptoms. This was followed by 30 min of ILF Neurofeedback. The primary placements were at T4-P4 for calming his hypervigilance and high arousal issues, followed by T3-T4 for system stability. To restore prefrontal control of his emotions, especially anger and rage outbursts, we used T4-Fp2, followed by T4-P4. He made rapid progress, as attested to by his own inter-session reports, and his wife. She came in at the fifth session, wanting to know what we were doing because, "I now have my husband back." After the tenth session on June 29, he retook PCL-5 and his score was 59; a reduction of 12 points in 5 weeks4. He claimed that his most troublesome symptoms had disappeared and that he was titrating off his medications. He penned a testimonial saying that he had received more benefit from 10 sessions of Neurofeedback than from 2 years of VA care. He e-mailed it to each of his VA therapists and prescribing doctors. However, he knew he was not "cured," and so he opted to continue with the Neurofeedback sessions, though at lesser frequency. First, we reduced it to twice a month, then to once a month as his work duties as Assistant Prosecuting Attorney increased. Being busy kept him from ruminating on his survivor guilt and he continued to see progress in his day-to-day activities and behaviors. He was still having some nocturnal flashbacks and nightmares. That was a sign that we needed to work on resolving the deep-seated trauma memories. We added two channel sum training at Fz + Pz at 0.05 mHz, and this was helpful for him. His wife reported that a drunken driver had crashed his car into the stone retaining wall in front of their house, but that her husband wouldn't bother to get up, saying the police could handle it. She commented that if this had happened before he started Neurofeedback, he would have been up immediately with the two guns he kept under his pillow to "deal with the threat." Since nightmares were still occurring, albeit infrequently, this indicated that the deep-seated state memories of the trauma had not been resolved. He also reported that he was still uncomfortable in crowds and avoided social gatherings. "Suspicious looking packages" still triggered a physiological arousal response. We decided to add two-channel sum Alpha Theta training with alpha frequency set at 10 Hz and theta set at 7 Hz, to aid in psychological resolution. There is a choice of scalp locations for this kind of training. In his case, after successful calming and restoring brain stability, we used P3 + P4, alternating from session to session with O1 + O2. A recorded guided imagery induction was added to engender a deep relaxation state. After one session, he said that he had "seen" the trauma sequence during his session, which he described as "movie scene without the emotional soundtrack." Immediately after the session he was able to calmly verbalize what had happened during the trauma incident for the first time. This was evidence that he had successfully decoupled the state memory and could now see the historical memory without triggering physiological arousal (See Figure 1). This veteran continued a schedule of monthly "refresher" sessions. Eighteen months into his rehabilitation from PTSD, he announced that was going to campaign for the position of Prosecuting Attorney, which he won. He acknowledged to me that he could never have campaigned or spoken in front of crowds prior to Neurofeedback training. He and his wife have continued to come for occasional joint sessions to "keep the stress down." In summary, this client was highly motivated to overcome the burden of his PTSD symptoms. This is not true for all the veterans I have trained with Neurofeedback. Some who live at some distance were unwilling to commit themselves to the intensive regimen to which this veteran agreed. Other veterans who depend on the VA disability checks had quit therapy because they feared losing their benefits if they got well. The determination and resiliency of this veteran, his trust in me, and faith in the method clearly contributed to his success. As the training proceeded, I could observe the visible change from the man who appeared pained, depressed, and hopeless when he first came in, to the person who found life to be interesting, challenging, and enjoyable. He and his wife have revitalized their marriage. They display affection and an easy back and forth humorous banter every time they come in for a "refresher session" more than 10 years after his initial visit. Neurofeedback is a non-invasive behavioral training that trains neuronal networks to improve self-regulation. It thereby ameliorates symptoms of PTSD while simultaneously reducing comorbidities. The above brief review of select programs are proof of concept that addictions, PTSD from combat or from torture, as well as mTBI and their dysregulating sequelae can be successfully remediated with the combination of ILF Neurofeedback and Alpha-Theta training. Each of the programs reviewed had shown positive results in a relatively short time along several dimensions: - Neurofeedback dramatically improves retention in existing drug/alcoholism rehabilitation programs, reduces recidivism, and promotes abstinence in PTSD/substance abuse comorbid veterans, and is free of from side effects and withdrawal issues of pharmaceuticals. - Neurofeedback training demonstrates positive influence in restoring dynamic functional connectivity in the principal resting state network, the Default Mode Network (DNM) as well as improved functional connectivity overall (Lanius et al.,). This attests to the positive impact of Neurofeedback on global functioning of the brain. It speaks both to the interconnectivity of neural networks, and neural plasticity of the brain. - The concomitant release from fear based hyper-vigilance, anchored in the trauma memories embedded in the physiology of the body, can bring positive transformative behavioral and emotional changes. - The development of the infra low frequency protocols has proven to be a highly successful improvement for the use of Neurofeedback as shown by the success of the last four studies cited above (Othmer and Othmer,). - Alpha-Theta Neurofeedback training has proven to be an effective method for opening a window into traumatic memories without emotional abreaction. This allows those unresolved memories to be released and processed with less risk of client re-traumatization that is common in talk or exposure therapy (Lake,). - Neurofeedback has proven to be superior to so-called "evidence-based" PTSD treatment in terms of effectiveness, temporal efficiency, and cost (Fragedakis and Toriello,; van der Kolk,). - A collateral benefit is the reduced risk of secondary trauma for the clinician. Collectively, clinical experience has demonstrated that trauma of whatever source can be successfully remediated with Neurofeedback, particularly when ILF NF is combined with more standard EEG-band protocols. Given the success as illustrated above, it is to be hoped that ILF Neurofeedback and Alpha-Theta training become accepted as part of an integrative and holistic approach for treating survivors of trauma.

neurofeedback, ptsd, alcoholism and alpha theta training, biofeedback, mtbi and neurofeedback, relapse prevention, torture and neurofeedback, trauma

PMC6529707_03

Male

A 40 year-old Guatemalan man with HIV/AIDS (CD4 count 26) not on antiretroviral therapy for the last eight months presented with ten days history of weight loss, vomiting, cough and night sweats. On examination he looked cachectic and frail. The temperature was 103F (39.4 C), the blood pressure 106/93 mm Hg, the pulse 121/minute, the respiratory rate 27/minute, and the oxygen saturation 100% while he was breathing ambient air. He had generalized weakness and anasarca. A diffuse macular rash was present as well as tender splenomegaly and inguinal lymphadenopathy. A CT scan of the chest, abdomen and pelvis revealed lower lobe pulmonary nodules, splenomegaly (22cm), enlarged axillary, inguinal and mesenteric lymph nodes. He was transferred to the ICU for suspected severe sepsis and disseminated intravascular coagulation (INR was 3, D-dimer 15 mcg/mL and fibrinogen 100 mg/dL). On complete blood count analysis he had a WBC 2.0 (normal 4.0-10.0 x 10/L), hemoglobin 7 (normal 14-18 g/dL), and platelets 30 (normal 150-450 x 10/L). His ferritin level was 4200 (normal 23.9-336.2ng/mL) and lactate dehydrogenase 1390 (normal 140-271 U/L). The level of interleukin 2 (IL-2) receptor alpha was elevated at 1314 (normal range 223-710 U/mL). Serum triglycerides level was normal. Routine blood culture showed no bacterial or fungal growth. Interferon-gamma release assay for tuberculosis was negative. Hepatitis A, B and C serologic tests were negative. Autoimmune workup included ANA, ANCA and rheumatoid factor were all negative. Cryptococcal Ag, Francisella tularensis IgG, Rickettsia rickettsii IgG and IgM, Trypanosoma cruzi IgM and Toxoplasma gondii IgM were all negative. Serology was positive to CMV IgG and PCR, but no baseline test was available to compare. Positive EBV IgG and EBV nuclear Ag IgG was consistent with past infection or a reactivated EBV infection. Acid-fast bacilli stain was negative and cultures remained negative for other common and opportunistic infections (PCP, CMV, HSV were all negative). Buffy coat fungal culture and stain was consistent with histoplasma. Bronchoscopy with BAL was positive for intracellular organisms with morphology consistent with histoplasmosis on Grocott-Gomori's methenamine silver stain. Liposomal amphotericin B was added to the empiric antibacterials immediately after the buffy coat test was reported positive. Atovaquone was started later and he continued on Azithromycin for chemoprophylaxis. Acyclovir was added for suspected CMV infection. HAART therapy (Darunavir, Dolutegravir, Emtricitab-Tenofovir) was started for his uncontrolled HIV infection one month after initiation of antifungals. A bone marrow biopsy was performed for evaluation of pancytopenia. The biopsy showed pancytopenia, increased iron stores, extensive intracytoplasmic fungi consistent with histoplasmosis and hemophagocytosis (Fig. 3). Cultures from the bone marrow aspirate confirmed disseminated Histoplasma capsulatum. Dexamethasone was started sixteen days after initiation of HAART therapy when the patient developed acute changes in his mental status. Although he initially improved, few days later his condition deteriorated. He developed septic shock with multiorgan failure secondary to MRSA pneumonia and disseminated Candida lusitaniae infection. Two and a half months after the diagnosis of histoplasmosis-induced hemophagocytic syndrome, supportive care was withdrawn and he succumbed to his illness due to HLH overlap with severe sepsis syndrome with multi-organ failure.

PMC4026149_01

Male

In February 2011 the 26-year-old male patient ("the case"), a never smoking professional soldier, was referred to the Department of Pneumology and Allergy with disseminated lung parenchymal changes. His chest X-ray was performed as part of a routine medical check-up before admission (Figure 1A). A previous X-ray taken 1 year earlier was normal. After his X-ray had been evaluated, he was admitted to the pulmonary unit of a district hospital, where lung CT scans were performed (Figure 1B). Bronchial aspirate examined for the presence of Mycobacterium tuberculosis taken at this time, both direct smear (Ziehl-Neelsen stain) and in culture (Lowenstein-Jensen medium) were negative. His tuberculin skin test (TST) was also negative (0 mm). Based on the clinical and radiological picture, stage II sarcoidosis was suspected, and he was referred to the Department of Pneumology and Allergy, Medical University of Lodz for further diagnosis. Although BAL fluid cellular pattern and laboratory results were not typical for sarcoidosis (Table 1), transbronchial lung biopsy (TBLB) revealed non-caseating granulomas (Figure 1C), confirming the initial diagnosis. Due to asymptomatic course, normal lung function and lung diffusing capacity for CO (DLCO) and lack of extra-pulmonary locations, the decision of treatment was suspended and the patient was asked to visit the out-patient pulmonary clinic within 3 months. In the meantime, 8 weeks after the collection, BAL fluid culture for Mycobacterium tuberculosis appeared positive. He was referred to a regional tuberculosis clinic and anti-TB treatment composed of isoniazid, rifampicin, pyrazinamide, and ethambutol was started according to directly observed treatment short-course strategy. The household members (the case's mother and twin brother) were asked to visit a regional TB out-patient clinic for routine examination of household contacts. Chest X-ray revealed disseminated parenchymal changes with enlarged hili in both family members. The previous X-rays of the twin brother and mother had been performed 3 months and a year ago, respectively, and were both normal. The chest X-ray of the case's older brother, who was living separately, was normal. Therefore, the mother and twin brother were referred to the Department of Pneumology and Allergy for further diagnosis. Chest CT scans confirmed the presence of bilateral hilar enlargement and disseminated nodular changes and thickening of bronchovascular bundles with predominance of upper and middle zones (Figures 2, and 3A). BAL cellular pattern was typical for sarcoidosis (Table 1) in both. TBLB of the case's twin brother was non-diagnostic (normal lung structure) and he refused further invasive examinations. The mother's TBLB showed non-ca-seating granulomas (Figure 3B). BACTEC examination of BAL fluid was negative in both the case's mother and twin brother. Due to asymptomatic course, well-preserved lung function, and lack of extrapulmonary symptoms, they were left untreated. Anti-TB treatment was also abandoned. At a follow-up in November 2011, the chest X-ray of the case was not different from the initial X-ray, but lung HRCT done in March 2012 showed substantial regression of parenchymal changes and sustained slightly enlarged mediastinal lymph nodes (picture not shown). Chest X-ray of the case's twin-brother performed in November showed complete regression of the previously described changes. The mother's chest X-ray performed at this time showed neither progression nor regression. Laboratory markers (SACE, CRP, serum calcium, liver function tests, and peripheral blood count) were within normal limits in all 3 patients. Twenty-four hour urinary calcium loss was increased in the mother but was normal in both twin brothers. Blood for QuantiFERON-TB testing was taken in November 2011 and the results were negative in the whole family. MTB were not found in lung biopsies of any family members (Ziehl-Neelsen stain).

mycobacterium tuberculosis, sarcoidosis, tuberculosis

CT-scan of the case's twin brother showing enlarged hilar lymph nodes and disseminated micronodules.

PMC4026149_01

Male

In February 2011 the 26-year-old male patient ("the case"), a never smoking professional soldier, was referred to the Department of Pneumology and Allergy with disseminated lung parenchymal changes. His chest X-ray was performed as part of a routine medical check-up before admission (Figure 1A). A previous X-ray taken 1 year earlier was normal. After his X-ray had been evaluated, he was admitted to the pulmonary unit of a district hospital, where lung CT scans were performed (Figure 1B). Bronchial aspirate examined for the presence of Mycobacterium tuberculosis taken at this time, both direct smear (Ziehl-Neelsen stain) and in culture (Lowenstein-Jensen medium) were negative. His tuberculin skin test (TST) was also negative (0 mm). Based on the clinical and radiological picture, stage II sarcoidosis was suspected, and he was referred to the Department of Pneumology and Allergy, Medical University of Lodz for further diagnosis. Although BAL fluid cellular pattern and laboratory results were not typical for sarcoidosis (Table 1), transbronchial lung biopsy (TBLB) revealed non-caseating granulomas (Figure 1C), confirming the initial diagnosis. Due to asymptomatic course, normal lung function and lung diffusing capacity for CO (DLCO) and lack of extra-pulmonary locations, the decision of treatment was suspended and the patient was asked to visit the out-patient pulmonary clinic within 3 months. In the meantime, 8 weeks after the collection, BAL fluid culture for Mycobacterium tuberculosis appeared positive. He was referred to a regional tuberculosis clinic and anti-TB treatment composed of isoniazid, rifampicin, pyrazinamide, and ethambutol was started according to directly observed treatment short-course strategy. The household members (the case's mother and twin brother) were asked to visit a regional TB out-patient clinic for routine examination of household contacts. Chest X-ray revealed disseminated parenchymal changes with enlarged hili in both family members. The previous X-rays of the twin brother and mother had been performed 3 months and a year ago, respectively, and were both normal. The chest X-ray of the case's older brother, who was living separately, was normal. Therefore, the mother and twin brother were referred to the Department of Pneumology and Allergy for further diagnosis. Chest CT scans confirmed the presence of bilateral hilar enlargement and disseminated nodular changes and thickening of bronchovascular bundles with predominance of upper and middle zones (Figures 2, and 3A). BAL cellular pattern was typical for sarcoidosis (Table 1) in both. TBLB of the case's twin brother was non-diagnostic (normal lung structure) and he refused further invasive examinations. The mother's TBLB showed non-ca-seating granulomas (Figure 3B). BACTEC examination of BAL fluid was negative in both the case's mother and twin brother. Due to asymptomatic course, well-preserved lung function, and lack of extrapulmonary symptoms, they were left untreated. Anti-TB treatment was also abandoned. At a follow-up in November 2011, the chest X-ray of the case was not different from the initial X-ray, but lung HRCT done in March 2012 showed substantial regression of parenchymal changes and sustained slightly enlarged mediastinal lymph nodes (picture not shown). Chest X-ray of the case's twin-brother performed in November showed complete regression of the previously described changes. The mother's chest X-ray performed at this time showed neither progression nor regression. Laboratory markers (SACE, CRP, serum calcium, liver function tests, and peripheral blood count) were within normal limits in all 3 patients. Twenty-four hour urinary calcium loss was increased in the mother but was normal in both twin brothers. Blood for QuantiFERON-TB testing was taken in November 2011 and the results were negative in the whole family. MTB were not found in lung biopsies of any family members (Ziehl-Neelsen stain).

mycobacterium tuberculosis, sarcoidosis, tuberculosis

Radiological and histopathological results of thecase's mother;. CT-scan showing enlarged hilar lymph nodes, and ,disseminated micronodular changes.

PMC6251325_01

Female

A previously healthy 43-years-old woman living in pasturing area, with no personal or family history of immunodeficiency, presented with a 2-months history of intermittent fever that was sometimes accompanied with chill, abdominal pain, diarrhea and hematochezia. The woman reported to a local hospital initially, where she was diagnosed with inflammatory bowel disease and treated with clindamycin, resulting in some clinical improvement. When her previous symptoms deteriorated for 10 days, she was seen at the Gastroenterology Department at our hospital. An X-ray of patient's abdomen at out-patient department showed signs of "incomplete intestinal obstruction" and she was admitted for further evaluation. Her physical examination was unremarkable, except for low blood pressure (97/71 mmHg) and a pale appearance. There was no self-reported loss of weight/appetite or other significant clinical findings at initial presentation. The laboratory tests at this initial presentation are summarized in Table 1. The patient was treated with anti-infective and symptomatic therapy initially. An enhanced-CT scan performed on day 2 in the hospital showed diffusible change in ascending, transverse and descending colon mimic ulcerous colitis. Multiple lymph nodes of mesenteric and posterior-peritoneum areas were visible (Figure 1). An emergency colonoscopy examination was suggested, which revealed multiple, discrete ulcers with irregular boundaries and clean base, scattered throughout the colon. The diameters of ulcers varied from 6 to 30 mm and errhysis could be seen around the erosion. Normal mucosa was also clearly visible amid the ulcers (Figure 2). The specific clonoscopic presentation made a strong indication of inflammatory disease including Ulcerative colitis (UC) and Crohn Disease (CD). Specific infectious bowel disease, especially intestinal tuberculosis, was also suspected because of patient's persistent fever, and the intestinal lymphoma diagnosis also could not be excluded. Further laboratory tests were done, including, chronic inflammatory enteropathy combination, anti-nuclear antibody (ANA), anti-neutrophil cytoplasmic antibodies (ANCA), rheumatism related factors (ASO+RF+ CRP), tumor markers of digestive tract, procalcitonin (PCT), blood culture, stool culture, amebic trophozoite detection, cytomegalovirus (CMV), anti-EBV antibodies, T-cell spot experiment and PPD test for Mycobacterium tuberculosis, Widal reaction, anti-Brucella antibodies, hepatitis virus indicators, Fungi D glucan detection, etc. Results for all of these tests were either negative or unremarkable, except for the high EBV-related antibody titers: anti-EBV viral capsid antigen (VCA)-IgG: (4.157 s/co), anti-EBV VCA-IgM (0.391 s/co), Epstein barr nuclear antigen (EBNA) IgG (0.865 s/co), EBEA IgG (1.933 s/co), and Epstein barr early antigen (EBEA) IgM (0.187 s/co). Patient showed no signs of remission during hospitalization. On day 10, a color Doppler ultrasound of abdomen showed splenomegaly. Patient developed severe intestinal bleeding 14 days after admission and underwent an emergency total colectomy, terminal ileum ectomy, small intestine and rectum anastomosis and preventive ileostomy. She was discharged after stable condition and was treated with mesalazine for ulcerative colitis (UC), based on the post-surgery pathological diagnosis made by our hospital. Mesalazine was stopped after a few courses. Capital Medical University-affiliated Beijing Friendship Hospital made a histological diagnosis of EBV T-cell LPD (II: Borderline) after histological examination of the resected tissue. Microscopic examination of resected colon slides revealed ulceration of intestinal mucosa and intestinal interstitial edema, which was accompanied by diffuse infiltration of small-to-medium-sized pleomorphic mild atypical lymphoid cells within mucosa and submucosa with a mixture of plasma cells and eosinophilic granulocyte and tissue cells. Some of the lymphoid cells had big nucleus and more obvious nucleoli. Lymphoid cells were observed to be distributed in muscular layer and serosa (Figure 3). We confirmed the diagnosis of EBV-associated T-cell LPD, based on the results from immunohistochemistry (IHC) and in situ hybridization of EBV-encoded miRNA (EBER). IHC revealed that the mild atypical lymphoid cells were positive for (Figure 4B) CD3, (Figure 4A) CD2, (Figure 4E) CD7, and (Figure 4C) CD4 expression. Further, a few atypical cells were also found positive for (Figure 4F) CD8, (Figure 4H) GranzymeB, (Figure 4J) TIAI, TCRGbeta, and TCRgammadelta. The lymphoid cells were negative for CD56. (Figure 4I) Ki-67 positivity was 40-50%. In situ hybridization for (Figure 4K) EBER demonstrated EBV-positive atypical lymphoid cells of 50/HPF. The patient was recommended to come back to hospital monthly for reexaminations. During these visits, she had signs of relapse every time, including new stoma ulcers and bloody stools. EB viral load test was done during her first follow-up visit, and EBV-DNA was found to be 2.55 x 106 copies/ml for. A post-operative colonoscopy, performed at first relapse, showed multiple aphthous bleeding ulcers scattered from the stoma to about 40 cm away from small intestine, in addition to colonic post-operative anastomositis (Figure 5). Histological examination of biopsy samples confirmed the pathological diagnosis of EBV-T-cell LPD. Treatment with daily prednisolone 10 mg was initiated intravenously for a few days in the hospital. Oral prednisolone, 40 mg/day, was prescribed thereafter, after which it was tapered off slowly. The patient showed significant clinical improvement. Hematochezia was temporarily controlled until when the prednisolone was tapered off to 25 mg, and EBV-DNA decreased to 1.31 x 106 copies/mL. Moreover, nothing remarkable was observed in colonoscopy this time (Figure 6). A bone marrow aspiration was strongly recommended but was not performed because of family refusal. The last time patient came back to our department for reexamination was 4 months after her initial presentation. During this last visit, bone marrow aspiration was performed and found to be normal. However, liver function tests turned out to be abnormal (ALT 100 IU/L and AST 43 IU/L). EBV-DNA was 1 x 106 copies/mL. The patient was referred to the Oncology Department of our Hospital for evaluation. She was asked to continue with the combination of prednisolone and anti-viral medication, until she presented with persistent fever and hematochezia, and died, 3 months later.

epstein-barr virus infection, t-cell lymphoproliferative disease, clinical features, differential diagnosis, endoscopic features

PMC9532611_02

Female

In the second kindred, a 6-year-old child (patient 4) with female phenotype presented for incidentally diagnosed increased blood pressure during a school health check. Her weight and height were 49 kg (3 SDs above the mean) and 136 cm (2 SDs above the mean), respectively. The bone age of patient 4 was approximately 6 years. In kindred 3 (patient 5), the parents noted that the child had with a vulva, but no vagina. However, testicular masses were palpable in the respective inguinal regions. The child underwent surgical exploration, which revealed that a vagina was absent and right and left masses were confirmed to be testes. Blood tests were performed according to standard methods. Blood hormone, Adrenocorticotropic hormone (ACTH), plasma renin activity (PRA), aldosterone (ALD), 17alpha-hydroxyprogesterone (17OHP) AMH (anti-Mullerian hormone), and inhibin B (INB) were measured by chemiluminescence; cortisol (F) was measured by electrochemiluminescence; dihydrotestosterone (DHT), and androstenedione (AD) were measured by liquid chromatography-mass spectrometry; dehydroepiandrosterone (DHEA), luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol (E2), testosterone (T), progesterone (P), and prolactin (PRL) levels were measured by enzyme-linked immunosorbent assay (Table 1). With the consent of the patient's parents, we collected the peripheral blood of the patients and their parents in three families. In addition, in family 1, peripheral blood of the proband's sister was collected. Later, DNA was extracted, next-generation sequencing (NGS) sequencing was performed for the probands. The observed variants in the probands were confirmed and the family members were screened for the respective variants by Sanger's method. A minimum of 3 mug DNA was used to prepare indexed Illumina libraries (MyGenostics, Beijing, China), according to the manufacturer's protocol. The exons of genes associated with congenital adrenal hyperplasia (all the genes including ABCD1 AIRE ARMC5 CDKN1C CYP11A1 CYP11B1 CYP11B2 CYP17A1 CYP21A2 DHCR7 GK GK2 GLCCI1 GNAS H6PD HESX1 HSD11B1 HSD3B2 LHX4 MC2R MCM4 MEN1 MKS1 MRAP NNT NR0B1 NR3C1 NR5A1 PCSK1 PDE11A PDE8B POMC POR PRKACA PRKAR1A PROP1 REN RXRA RXRB SOX3 STAR TBX19 TP53 TXNRD2) were targeted via a gene capture strategy, using the GenCap custom enrichment kit (MyGenostics), according to the manufacturer's protocol. The enriched libraries were sequenced on a NextSeq 500 sequencer (Illumina, San Diego, CA, USA) to generate paired-end reads of 150 bp. Single-nucleotide polymorphisms, insertions, and deletions were identified using Genome Analysis Toolkit software.

17α-hydroxylase deficiency, children, hypertension, hypokalemia, novel variant, twin

PMC8168707_01

Male

A 52-year-old Hispanic male presented from an outside hospital with head computed tomography (CT) concerning for spontaneous SAH. The patient was initially brought to an outside hospital after he was found unresponsive by his family following a bout of coughing earlier that morning. CPR was initiated for 5 min before EMS arrival, with the patient experiencing a single episode of vomiting and bladder incontinence before regaining consciousness. His family noted that the patient had complaints of chills, a mild cough, and sore throat the night before admission but was otherwise he was in his normal state of health. He had no history of prior tobacco use and otherwise had a medical history significant for hypertension without current pharmacologic treatment. There was no family history of aneurysms or any reported viral prodrome within his family contracts. His baseline modified Rankin scale (MRS) was 0. On arrival to our institution, the patient had no complaints other than a mild headache and neck pain. Initial vitals were significant for a temperature of 39.8 C, blood pressure 157/95 mmHg, and oxygen saturation of 93% on room air. Clinical examination was notable for some mild confusion, but otherwise there were no cranial nerve deficits or focal findings on clinical exam. A noncontrast head CT demonstrated extensive SAH in the basal cisterns around the midbrain extending into the left Sylvian fissure with mild prominence of the bilateral temporal horns [Figure 1]. CT angiogram (CTA) of head and neck demonstrated a small left posterior communicating (p-comm) aneurysm [Figure 2] along with bilateral airspace disease at the lung apices, compatible with pneumonia [Figure 3]. An incidental, small right cavernous segment aneurysm and anterior communicating segment fusiform dilation were also noted. Clinical grading was consistent with a Hunt-Hess grade of 1+1 (hypertension) and modified Fisher grade of 3. Laboratory values showed no leukocytosis, platelets 125 10e9/L, sodium 135 mEq/L, BUN 14 mg/dL, and Cr 0.7 mg/dL. Liver function and coagulation studies were within normal ranges except for d-dimer, which was elevated at 1.4 mg/L (UNL 0.59) and fibrinogen, elevated at 451 mg/ dL (UNL 440). Coronavirus PCR was positive. An external ventricular drain was placed with an opening pressure 21 mmHg. The patient was intubated before being taken to the neurointerventional suite for treatment. Diagnostic cerebral angiography of the left internal carotid artery (ICA) revealed a dominant left p-comm artery filling the posterior cerebral artery on the left with small aneurysm emanating from the junction of the left ICA and left p-comm artery, pointing posteriorly and inferiorly measuring 4 x 6 x 4 mm [Figure 4]. There was no daughter sac or evidence of extravasation of contrast. A total of six Gugliemi detachable coils (GDCs) were placed within the aneurysm leading to >95% aneurysm obliteration. A total of six Gugliemi detachable coils (GDCs) were placed within the aneurysm leading to > 95% aneurysm obliteration [Figure 5]. The patient tolerated the procedure well. He was extubated and taken to the neurological ICU (NICU) in stable condition where he was monitored for complications of SAH. A 10-day course of empiric antibiotics was completed for aspiration pneumonia. Over the course of his stay, his neurological status remained stable, however, he developed progressive hypoxemic respiratory failure and required intubation on hospital day 4 (postbleed day 3). Convalescent plasma and dexamethasone at 6 mg daily were initiated on hospital day 4, while remdesivir was held as the replication phase had passed. His initial high PEEP and FiO2 demands were weaned and he was successfully extubated on hospital day 15 and his ventricular drain removed on hospital day 13. He had no evidence of vasospasm and was downgraded from the ICU on hospital day 16. Clinically at the time of downgrade, the patient was GCS14, e4v4m6, with some intermittent confusion but otherwise appropriate without cranial nerve or any lateralizing motor deficit.

aneurysm rupture, covid-19, cerebral aneurysms, subarachnoid hemorrhage

Axial CT through the lung apices demonstrating multifocal bilateral airspace disease compatible with pneumonia.

PMC8168707_02

Male

A 61-year-old Hispanic male was transferred from an outside facility when he was found by his wife after falling in the bathroom earlier that morning. At the outside institution, he reportedly had a GCS of 8 (unknown breakdown) and was for declining mental status. CT head demonstrated prominent SAH in the basal cisterns [Figure 6] and CTA demonstrated a bilobed anterior communicating artery aneurysm [Figure 7]. Clinical grades demonstrated HH4+1 and mFG4. His medical history was significant for hypertension, previous craniotomy from a gunshot wound to the head, prior heroin abuse, and hepatitis C. He had tested positive for COVID-19 approximately 2 weeks before admission, though asymptomatic. Baseline MRS was 0 with no family history of aneurysms. On arrival to our institution, he was afebrile, with BP 164/100 mmHg and saturating 100% on 40% FiO2. Clinically, he was intubated with a GCS of 8T (e2vTm5), with a prosthetic right eye but otherwise with intact cranial nerves. He was localizing to pain in his left upper extremity and withdrawing in all other extremities. Laboratory values were significant for leukocytosis of 18.0 10e9/L and sodium 135 mEq/L. Liver function test and coagulation were within normal limits. A right frontal ventriculostomy was placed and he was started on levetiracetam, nimodipine, and high-dose rosuvastatin for vasospasm protection. On postbleed day 1, he was taken to the interventional suite for coiling. Diagnostic angiography of the left ICA revealed a large multilobulated bulbous aneurysm of the anterior communicating artery [Figure 8]. Coil embolization was successful with complete aneurysm obliteration with minimal contrast filling along the neck and no evidence of occlusion of either the communicating segment or the distal A2's or proximal A1 segments right and left sides [Figure 9]. Postprocedure, the patient returned intubated to the ICU with a stable neurological examination. He was successfully extubated on hospital day 2 and spiked a fever on hospital day 5-38.4 C, but otherwise remained afebrile during his hospital course. Ventricular drain weaning was unsuccessful and a right frontal ventriculoperitoneal shunt was placed on hospital day 20. He was downgraded from the ICU on hospital day 22 with no evidence of vasospasm. Clinically, he was a GCS of 14, e4v4m6. He would intermittently converse but remained confused. Cranial nerves were intact and he would intermittently follow simple commands in all extremities with no lateralizing motor deficits.

aneurysm rupture, covid-19, cerebral aneurysms, subarachnoid hemorrhage

PMC8294436_01

Female

A 21-year-old female presented to the department of dermatology with chief complaints of gradually progressive yellowish lesions which started around 14-15 years back, first started around eyes and then progressed to neck, hands, arms and legs. The family history revealed the presence of similar symptoms in her elder brother (died 6 years back because of sudden myocardial infarction) and maternal uncle's son. On clinical examination, multiple cutaneous lesions were present including planar xanthomas, tuberous xanthomas, xanthelasma, and corneal arcus [Figure 1]. She was first provisionally diagnosed with hypercholesterolemia at the age of 15 years and was put on lipid-lowering drug statins (5 mg daily) for 1 year and later the dose was escalated to 40 mg daily. At our hospital, she was admitted for radiofrequency ablation and biopsy of the cutaneous lesion in the cubital fossa under department of dermatology. She was further referred for cardiology consultation and her blood investigations were ordered. All her laboratory parameters including complete blood count, serum electrolytes, renal function tests, blood glucose, and liver function tests were normal except lipid profile. Her total serum cholesterol and LDL-C were 717.2 mg/dl and 690.6 mg/dl, respectively. Her treadmill test was positive for inducible myocardial ischemia, and the computed tomography angiogram revealed triple-vessel disease with 100% occlusion of the right coronary artery. Immediately, treatment was started with 80 mg atorvastatin along with other drugs such as ecosprin, clopidogrel, metoprolol, and nitroglycerin. The department of transfusion medicine was contacted for LDL apheresis in view of coronary involvement and high serum cholesterol levels. A cascade filtration (CF) plasmapheresis was performed using plasma fractionator (Evaflux 5A20, Kawasumi Laboratories Inc.) with cell separator (COBE Spectra, Terumo Penpol) to withdraw plasma [Figures 2 and 3]. Glicher's rule of five was used for calculation of total blood volume (TBV), and total plasma volume (TPV) was calculated as TBV x (1-hematocrit). As the patient weighed 37 kg, her TBV and TPV were 2405 ml and 1527 ml, respectively. The right femoral vein was used as venous access for procedure using double-lumen femoral catheter. The inlet blood flow rate was kept between 35 and 37.7 ml/min during the procedure. Acid citrate dextrose-A was used as an anticoagulant at a ratio of 1:14, and no replacement fluid was used during the procedure as her own plasma was being returned after getting treated through the fractionator column. The procedure was uneventful till the processing of 1.2 plasma volume (1882 ml), when the patient's blood pressure dropped to 70/50 mmHg. The procedure was then halted, normal saline bolus was given, and the procedure was ended with rinseback and the patient was shifted to ward in stable condition. The postprocedural total cholesterol and LDL-C levels were 211 mg/dl and 156 mg/dl, respectively [Figure 4]. Because of financial constraints, the patient could not return for further procedures and enrolled in a free cardiac drug trial. The lipid profile post 12 weeks of drug trial therapy showed raised total serum cholesterol and LDL-C (553 mg/dl and 500 mg/dl, respectively).

cardiovascular disease, familial hypercholesterolemia, lipoprotein apheresis, low-density lipoprotein cholesterol, xanthomas

PMC6560332_01

Male

A 34-year-old man presented with high-grade fever with chills and rigors and left-sided pleuritic type chest pain associated with a lump in the anterior chest wall. He was a patient with stage 5 chronic kidney disease and was on regular hemodialysis through an arteriovenous fistula during the past one year. He was awaiting kidney transplantation. On examination, he was febrile with a temperature of 38.7 C. There were multiple enlarged tender axillary lymph nodes on the left side. The lymph nodes were around 0.5 cm and mobile and deep seated. He was dyspneic, breath sounds were reduced in the left lower zone of the lung with few crepitations. There was a tender lump (5 x 5 cm) on the left anterior chest wall. Other system examinations were found to be normal. Approximately four months prior to the aforedescribed admission, he was investigated previously for fever, poor appetite, and loss of weight lasting for one-month duration. Clinical examination had revealed crepitation in the left lower lung base. Investigations done during that previous admission had revealed normal full blood count, erythrocyte sedimentation rate (ESR) of 93 mm in 1st hour, and C-reactive protein at 23 mg/dl. Chest X-ray had shown evidence of left lower upper and lower lobe patchy opacities. He had been treated with IV co-amoxiclav 1.2 g three times daily empirically. As a further evaluation, contrast-enhanced computed tomography (CECT) of the chest was performed, which had revealed poorly defined small nodules and tree-in-bud opacities in the left lower lobe with focal consolidation in the apical segment of the left upper lobe in keeping with chronic lung infection. A small well-defined enhancing subpleural nodule with speculated margin in the posterior segment of the left lobe and few hilar and pretracheal enlarged lymph nodes were also seen. The Mantoux test had been 20 mm. Sputum direct smear for acid-fast bacilli (AFB) and culture had been negative. A tentative diagnosis of tuberculous infection had been done, and he was started on antituberculous therapy (ATT), namely, rifampicin, ethambutol, pyrazinamide, and isoniazid. After two weeks of ATT, the patient had developed Stevens-Johnson syndrome (SJS), and ATT was discontinued. His symptoms had improved with prednisolone 60 mg daily with tapering over the next preceding month, but ATT was not recommenced due to uncertainty of the diagnosis, because by that time, patient's symptoms had been resolved, and the sputum for tuberculosis (TB) culture was reported as negative. Investigations done during the latter admission revealed white cell count of 10,000 with neutrophils of 89%, lymphocytes of 10%, eosinophils of 0.2%, hemoglobin at 7.2 g/dl, mean corpuscular volume of 93 fl, and platelets 278 x 103. The erythrocyte sedimentation rate (ESR) was 101 mm in the first hour, and C-reactive protein was 311 mg/dl. Chest radiograph showed left lower zone effusion with consolidation (see Figure 1). Considering the history and the high inflammatory markers with X-ray changes, a possible diagnosis of left lower lobe pneumonia with parapneumonic effusion was considered. Initially, he was treated with IV co-amoxiclav 1.2 g three times daily. Sputum for gram stain, acid-fast bacilli, was found to be negative. Sputum for pyogenic culture also did not isolate any organism after 72 hours of incubation. Ultrasound-guided aspiration of the pleural fluid was carried out and aspirated purulent blood-stained fluid. Lymph node fine needle aspiration or biopsy was not considered for several reasons. First, as it was situated on the left axilla, where the patient had his fistula made for the hemodialysis. Second is that the lymph nodes were found to be too small for sampling. Third was since they were deep seated, and it was difficult to gain access, and lastly, because of the possibility of arriving at a diagnosis by evaluating the effusion where access is easily gained. The aspirate was analyzed with gram stain and AFB stain, which were negative. Pyogenic culture of the aspirate remained sterile after 72 hours. Full report of the aspirated fluid revealed 90% polymorphs and 10% lymphocytes. Lactate dehydrogenase (LDH) was 12,738 IU/l. Adenosine deaminase level (ADA) was 431 mu/l. Because of the high inflammatory markers and the neutrophil predominance, he was treated with intravenous (IV) meropenem 500 mg twice daily and with IV clindamycin 500 mg twice daily for two weeks. But since the ADA was very high, with relation to the past history, underlying tuberculosis infection was also considered. Therefore, aspirate fluid was sent for TB culture. While awaiting TB culture, subsequent CECT revealed empyema necessitans with destruction of the left side anterior upper rib associated with left pleural and mediastinal lymphadenopathy with the most probable infection of tuberculosis (see Figures 2 and 3). The patient was referred to the thoracic surgical team, and they carried out incision and drainage of the lump since the effusion was minimal by that time with the drainage and the treatments. Abscess wall histology did not reveal caseating granulomas. The abscess fluid culture isolated 19 colonies of Mycobacterium tuberculosis organism after one month of incubation; hence, tuberculous empyema necessitans was confirmed.

PMC10318104_01

Female

A 36-year-old woman presented in the emergency room with a history of central abdominal pain for 3 days and complaints of abdominal fullness and vomiting for the last 2 days associated with non-passage of flatus and feces. She also gave a history of evening rise in temperature and non-productive cough for the past 3 months. She was receiving antitubercular treatment for pulmonary tuberculosis, which was diagnosed 3 months back. Upon examination, she was found to be in distributive shock with mild pallor and a body mass index (BMI) of 17.8 kg/m2. The abdomen was distended, tender with muscle guard, and peristaltic sounds were absent. A contrast-enhanced CT (CECT) scan of the whole abdomen showed pneumo-peritoneum with ascites and dilated bowel loops. She was taken up for an emergency exploratory laparotomy, and during surgery 3 l of foul-smelling enteric fluid was drained and two perforations were found in the terminal ileum 60 cm proximal to the ileocecal junction. The 5 cm segment bearing the perforations was resected, and a double-barrel ileostomy was fashioned. Postoperatively, her stoma started functioning within 48 h, she was allowed a soft diet by the fifth day and was advised on restarting the ATD. She developed a deep surgical site infection (SSI) on the seventh day, which was managed by antibiotics and regular dressings. In the second week, she started developing recurrent bilious vomiting and a low-grade fever for which she was resuscitated with intravenous fluids, proton pump inhibitors, and prokinetics. She developed bilateral moderate pulmonary effusion and jaundice (total bilirubin 3.4 mg/dl), for which multiple percutaneous pleural taps were done, and she was started on second-line ATD. However, her bilious vomiting persisted even after stopping the first-line ATD. A gastroduodenoscopic examination revealed edematous but normal duodenal mucosa and a progressive luminal compromise until the third part (D3), beyond which the scope could not be negotiated suggestive of extrinsic compression. An attempt to negotiate a nasojejunal feeding tube beyond the D3 failed, and she was started on total parenteral nutrition. A CECT whole abdomen showed a distention of the proximal duodenum with air-fluid level and a transition point at the distal D3. There was no abnormal mural thickening, and the D4 and jejunal loops were found collapsed. The aorto-mesenteric angle was 16.5 (Figure 1) and the aorto-mesenteric distance was 6.38 mm (Figure 2), suggesting SMA syndrome. A trial of non-operative management was started due to her early postoperative status. She was nursed in the left lateral position with continuous nasogastric aspiration and parenteral nutritional support. In the third postoperative week, she started developing features of septicemia, and hypotension. She was placed on vasopressor support for persistent hypotension and intravenous injection of Meropenem and Metronidazole for septicemia to which she did not respond adequately. Histopathological report of the resected intestinal segment showed areas of inflammatory infiltrates with fungal colonies, and the fungal culture was positive for Candida spp., which was treated with systemic antifungal agents. By the end of the third week, due to the subsidence of mucosal edema, a nasojejunal feeding (NJ) tube could be placed endoscopically beyond the narrowed segment, and tube feeding was started. Gradually over the next week, she responded to treatment, her vomiting subsided, she became afebrile, and started tolerating a liquid diet. After the fifth week, she started tolerating a normal diet by mouth and was discharged. She registered an increase in body weight by almost 3 kg at the end of the second month of follow-up.

wilkie’s syndrome, fungal infection, medical therapy, postoperative nausea and vomiting, superior mesenteric artery syndrome

PMC5480006_01

Male

A 66-year-old male, originally from Puerto Rico, with no significant past medical history presented with three days of colicky upper abdominal pain associated with one episode of bright red blood mixed with stool. He reported subjective fevers with chills. He had new-onset intermittent constipation during the previous month. He denied nausea, vomiting, diarrhea, pruritus, weight loss, fatigue or jaundice. Family history was negative for colon cancer. He had no history of smoking or alcohol abuse; further, he denied any high-risk sexual behavior or any history of or exposure to tuberculosis and syphilis. The patient presented to an outside hospital with stable vital signs except for being febrile (38.3 C). Lab results showed leukocytosis and anemia. This was followed by an abdominal ultrasound that was suspicious for right colon mass and infrarenal aortitis. The patient was started on broad-spectrum antibiotics and transferred to our hospital. On arrival he was febrile to 38.9 C, but remained hemodynamically stable. Initial blood tests here showed white blood cells 19,500 cells/muL with 87% neutrophils, and hemoglobin 9.0 g/dL with a mean corpuscular volume 71 fL. HIV, liver enzymes, carcino-embryonic antigen and lipase were within normal limits. Computed tomography (CT) of the abdomen and pelvis confirmed infrarenal aortitis and a right colon mass (Fig. 1A, B). Colonoscopy revealed a 2-cm mass in the proximal ascending colon (Fig. 2A), as well as a 5-cm rectal mass (Fig. 2B). While both masses were grossly suspicious for malignancy, the rectal mass biopsy revealed only high-grade dysplasia. The right colon mass was not biopsied because a right hemicolectomy was already planned for the same day. The patient underwent transabdominal excision of the infected infrarenal abdominal aorta, as well as the proximal bilateral common iliac arteries and proximal inferior mesenteric artery, followed by reconstruction with aorto-iliac cryopreserved homograft and left renal artery re-implantation. An extended right hemicolectomy and end ileostomy were also performed. Cultures from blood and from the aorta grew C. septicum, sensitive to ampicillin-sulbactam. The right colon mass was an adenocarcinoma (Fig. 3A) (T3N0), negative for deficient mismatch repair protein expression, B-RAF (B-type rapidly accelerated fibrosarcoma) and K-RAS (Kirsten rat sarcoma oncogene) mutation but positive for N-RAS (neuroblastoma RAS oncogene). The patient was treated with IV ampicillin-sulbactam and improved clinically, with subsequent negative blood cultures. He was discharged four weeks after admission and completed an additional two weeks of IV antibiotics. Follow-up positron emission tomography CT scan revealed a focus of nonspecific increased metabolic activity in the peritoneal cavity and mesenteric lymph nodes. Three months later, after full recovery from the surgery and sepsis, the patient underwent trans-anal intramural excision of the rectal mass, which was an invasive adenocarcinoma on histology but negative for C. septicum. Tumor-free margins were achieved (Fig. 3B). The tumor was negative for deficient mismatch repair protein expression, B-RAF and N-RAS mutation, but positive for K-RAS. The patient had a low oncotype DX recurrence score (11) and was offered but declined adjuvant chemotherapy.

clostridium septicum, aortitis, colorectal adenocarcinoma

PMC4772633_01

Male

A 75-year-old Japanese male ex-smoker underwent four different video-assisted thoracoscopic surgeries for EGFR-mutated NSCLC and a pancreaticoduodenectomy for metastatic pancreatic tumor in 2006. In September 2014, he was diagnosed with metastatic thyroid tumor and received afatinib therapy in November 2014. Afatinib was the only chemotherapy administered to the patient. Two weeks after the initiation of an oral 40-mg afatinib dose, the patient developed bilateral conjunctival injection without discharge and was referred to ophthalmologists. The best-corrected visual acuity (BCVA) measurements showed there was a decimal visual acuity of 0.9 in the right eye and 1.0 in the left eye. Slit-lamp examination revealed there was bulbar conjunctival injection and incipient senile cataract in both eyes. During these examinations, there were no clinical signs that suggested the presence of uveitis. The conjunctivitis resolved shortly after the instillation of bromfenac 0.1% eye drops twice a day and a 1-week afatinib washout period. On the 3rd day after the patient resumed taking afatinib, he developed blurred vision in his right eye and once again visited his ophthalmologists. BCVA had decreased to a decimal acuity of 0.2 in his right eye, while it remained at 1.0 in his left eye. Slit-lamp examination revealed keratic precipitates, cells (1+) in the anterior chamber, two small Koeppe nodules on the nasal iris, posterior synechiae and mild vitreous haze in the right eye (fig. 1a). There was no inflammation observed in the left eye. Fundus examination revealed no remarkable findings, including metastatic choroidal tumor. Intraocular pressure elevation, dendritic or pseudo-dendritic corneal epithelial lesion, iris atrophy, or histories of recurrent HSV infection or skin eruption were absent. The results of a serologic test including full blood counts, liver enzymes, kidney function, electrolytes, fasting plasma glucose and hemoglobin A1C revealed only mild anemia. Serologic tests for syphilis were negative. A chest X-ray and CT scan showed no hilar or mediastinal lymphadenopathy, and no signs of tuberculosis. Human leukocyte antigen (HLA) typing revealed that the patient was HLA-B27 negative. Since the unexplained uveitis that developed after the administration of afatinib was similar to that which has been observed for erlotinib, we considered the possibility of afatinib-induced uveitis. Based on these findings, we stopped the general afatinib treatment and then restarted topical betamethasone 0.1% four times per day and mydriatics once per day. After the inflammation gradually subsided, the topical betamethasone 0.1% was then tapered to twice per day and the mydriatics were discontinued. Although oral afatinib at a dose of 30 mg was resumed after a 3-week washout period, the anterior uveitis in the right eye did not recur. The BCVA finally recovered to a decimal acuity of 1.0 after 6 months. However, the posterior synechiae remained (fig. 1b). There were no other structural complications observed.

afatinib, anterior uveitis, epidermal growth factor receptor, koeppe nodule, side effect, unilateral granulomatous anterior uveitis

PMC3568890_01

Female

A 9-year-old female primary 3 pupil presented at Federal Medical Centre, Umuahia, Abia State, South Eastern Nigeria, with a year history of recurrent cough (initially productive of bloody sputum but later became dry), 3 months history of recurrent fever, and generalized weight loss. There was no history of contact with a patient with pulmonary tuberculosis. The mother tested positive to HIV, while the blind father was HIV negative. On examination she was chronically ill looking and pale with generalized muscle wasting and hypopigmented spots. Investigations carried out included retroviral test, CD4, sputum acid-fast bacilli and chest X-Ray. The retroviral test was positive, and the CD4 count was 543 cells/uL. The chest X-ray was suggestive of pulmonary TB. The sputum acid-fast bacilli (AFB) result at presentation was 0, +. The diagnosis of retroviral disease was made first and pulmonary tuberculosis a month later. The patient was started on antituberculosis drug with category one regimen which includes rifampicin, isoniazid and pyrazinamide for 2 months and rifampicin and isoniazid for 4 months (2RHZ/4RH). After five months, the patient's sputum AFB was still positive and was declared a failure case. The category two regimen was then started with two months of streptomycin, rifampicin, isoniazid and pyrazinamide, one month of rifampicin, isoniazid, and pyrazinamide and 5 months of rifampicin and isoniazid (2SRHZ/RHZ/5RH) concurrently with antiretroviral drugs (zidovudine, lamivudine and efavirenz). However, at five months, the patient was still sputum AFB positive with results as follows: 6/100 and + and CD4 count of 268 cells/uL, and the patient was declared as failure case after retreatment. The patient was suspected as a case of multidrug-resistant TB and the sputum was collected and sent to a centre in Ebonyi State, South Eastern Nigeria, where there is instrument for investigation (Gene Xpert). The Gene Xpert was done and the result of multidrug resistant tuberculosis was positive. Since multi drug resistant cases are not managed in this particular centre the patient was referred to University College Hospital (UCH), Ibadan, South Western Nigeria, where facilities for management of MDR-TB cases are available and culture and DST were done to confirm the diagnosis. The patient is presently receiving treatment in UCH and responding very well. At the time this patient was referred to this centre, it was confirmed as the first paediatric multidrug-resistant case seen and needed to get the regimen for the management.

PMC5904811_01

Female

A 34-year-old woman presented with abrupt onset headache and lethargy attributable to an acute SAH secondary to a ruptured P-1 aneurysm. She received standard therapy for SAH patients and had successful coiling of the aneurysm. On postbleeding day 4, while hemodynamically stable, she developed a new drift in the right upper extremity that progressed to grade 3/5 motor weakness with facial weakness within 30 minutes. A repeat plain CT showed no hydrocephalus. The CT perfusion showed no derangement of the cerebral blood volume (CBV) or the cerebral blood flow (CBF) with a slightly prolonged mean transit time (MTT) denoting intact brain tissue. The time-to-peak (TTP), on the other hand, was significantly prolonged in the left central Rolandic subcortical region, consistent with the clinical finding (Figure 1). A Bowman Perfusion Monitor (BPM, Hemedex, MA, USA) was inserted at the bedside, using free-hand technique aiming at the point of interest generated by the CT perfusion TTP scan. The cerebral blood flow (CBF) measured at this time was 14 cc/100 g/min, denoting severe hypoperfusion (normal level is above 25 cc/100 g/min). The patient was started on the MNH-milrinone protocol for the treatment of vasospasm. Within 1 hour, the patient did not improve, necessitating endovascular vasodilator therapy, during which she received 2 mcg of milrinone over 3 minutes with immediate vasodilation of the vasospastic segment. The CBF reading improved to the 50's with the maintenance of milrinone. On 2 occasions, weaning the milrinone infusion was associated with an asymptomatic but significant drop of the measured CBF to low 20's, which delayed the weaning for 24-48 hours each time, likely related to recoil of angioplastied vessel mitigated clinically by the milrinone effect. The total monitoring period was 9 days, after which milrinone was stopped and CBF measurement ranged from 40 to 50 and the patient did not have any residual motor deficits for an additional 48 hours.

PMC3967267_01

Male

A 53-year-old male twisted his leg while downhill skiing and sustained an OTA classification 43-A2.3 (4) closed fracture of the distal tibia and fibula. Both fractures were treated with open reduction and locking plates in January 2009. A non-union developed with loosening of the osteosynthesis, and 7 months after the initial operation the patient was reoperated with bone allograft and exchange of the plates and screws. The non-union did not heal. The patient was referred to our institution 20 months after the first reoperation. At this time, the tibial plate was loose, with broken screws (Figure 1). The tibia had a varus deformity of 16 degrees and was 2.2 cm shortened (Figure 1). The non-union site was tested clinically and found to be loose. We operated the patient 24 months after the first reoperation. After removal of all previously inserted implants and screws, except a distal AP screw, the non-union site was found at surgery to be atrophic. The non-union site (3.1 cm bone segment) was resected to vital bone. The fibula was osteotomized at the level of the tibial resection. A proximal percutaneous tibial osteotomy was performed 9 cm from the knee joint line. A custom-made motorized tibial lengthening nail (Fitbone TSA (Tibial Segment Actuator) was inserted. The nail had a length of 35 cm and was capable of 4 cm of bone transport initially and 2 cm of bone lengthening subsequently. The nail had 8 degrees of anterior bending, starting 40 mm from the proximal tip of the nail. The nail was locked with 2 proximal and 2 distal locking screws to the tibia. In addition, a screw was inserted into a sliding hole in the middle part of the tibia, allowing bone transport of the middle tibial segment (Figure 2). A tibio-fibular screw was inserted distally to protect the distal tibio-fibular joint. Acute shortening of the bone defect was not performed. A radiograph taken immediately after surgery showed that 3.1 cm of bone had been resected. Bone transport was initiated 10 days postoperatively at a rate of 1 mm daily (Figure 3). There were no clinical signs of infection and the white blood cell and C-reactive protein levels were normal before surgery. However, biopsies of the resected bone were cultured and showed growth of coagulase-negative staphylococci, which were sensitive to dicloxacillin. Dicloxacillin was therefore administered orally for 3 months. 4 weeks postoperatively, 3.3 mg of recombinant BMP-7 (eptotermin alfa, Osigraft; Stryker) was administered percutaneously to the docking site. A loose proximal locking screw was exchanged at the same surgery and intraoperative fluoroscopy showed that the fibula osteotomy was still loose, allowing lengthening of the fibula. Partial weight bearing was allowed from 2 months postoperatively when the proximal tibia had been lengthened 5 cm (3 cm of bone transport plus 2 cm of leg lengthening). The docking site was united 5 months postoperatively, and full weight bearing was allowed at this time. Healing time for the regenerate was 45 days/cm of bone lengthening. The distal tibio-fibular screw bothered the patient and was removed at 6 months postoperatively. The nail was removed 15 months postoperatively. At the latest follow-up, 18 months after nail insertion and 3 months after nail removal, the patient had no pain or restrictions in daily activities. Motion of the knee and the ankle on the operated side was equal to that on the healthy side. Motion of the knee was from full extension to 140 degrees of flexion and motion of the ankle was from 15 degrees of dorsal flexion to 30 degrees of plantar flexion. An AP radiograph showed no mechanical axis deviation in the operated leg compared to the healthy leg. There was equal leg length. There was a 3-degree varus deformity in the frontal plane. There was no deformity in the sagittal plane on the lateral radiograph. The posterior proximal tibial angle (PPTA) and the anterior distal tibial angle (ADTA) equalled the preoperative values of 78 degrees (PPTA) and 83 degrees (ADTA). There have not been any clinical signs of infection.

PMC5392770_01

Male

A 24-year-old man presented with left-sided tightening chest pain for three days and a few hours of productive coughing with blood-clotted sputum. The patient reported unintentional weight loss during the last month, intermittent night sweats but no fever or lethargy. His medical history was unremarkable, and he took no medicine. He had previously smoked for six months. The patient, a refugee from a rural Syria, had lived in Denmark for one year. He was exposed to sheep and dogs during his childhood. General physical examination revealed fever, a temperature of 39 C, a heart rate of 76 beats per minute, a respiratory rate of 22 breaths per minute, and a blood pressure of 130/70 mm Hg. Apart from this, the clinical examination was unremarkable. Blood samples revealed an elevated CRP of 197 mg/l, leukocytosis (15.4 x 109/L) with a strong component of granulocytosis, but no eosinophilia. Chest X-ray revealed consolidation of the upper two thirds of the left lung (Fig. 1). Because of the medical history and possible exposure to tuberculosis, the patient was suspected to have pulmonary tuberculosis. Interferon-gamma release assay (IGRA) was taken and sputum was sent for microscopy; both were negative. A computed tomography scan (CT scan) of the thorax showed a cavitary lesion with septae and air-fluid-level with filaments measuring approximately 8 x 11 x 13 cm, involving the left superior lobe. Folded membrane-like structures within the cavity suggested a hydatid cyst. The air filling indicated that the cyst communicated with the airways. The rest of the lung fields and mediastinum appeared without pathology. (Fig. 2). A CT scan of the abdomen revealed no abnormality. The patient was prescribed antihelminthic treatment with albendazole 400 mg, two times daily. Blood samples tested with enzyme-linked immunosorbent assay (ELISA) for E. multilocularis and with indirect hemagglutination (IHA) for E. granulosus antibodies came out negative. Microscopy of sputum showed massive growth of Streptococcus pneumoniae, and it was concluded that the patient had a lung abscess. The patient was prescribed broad-spectrum antibiotics and albendazole was discontinued. Few days later the patient developed acute chest pain; chest X-ray (Fig. 3) showed atelectasis of the lower part of the left lung with an air compartment above the abscess and a small mediastinal shift away from the pleural effusion. CT-scan showed a ruptured lung abscess or cyst and hydropneumothorax of the left lung. The patient was treated with therapeutic thoracentesis, approximately 600 mL yellow liquid was removed and sent for microscopy. Due to respiratory distress the patient was transferred to our intensive care unit (ICU). After 24 hours of care in the ICU, the now stable patient was transferred to the pulmonary ward. A multidisciplinary team conference was held to discuss differential diagnoses, further investigations and management. The team concluded that further investigation with bronchoscopy was necessary. Microscopy and polymerase chain reaction (PCR) tests for E. granulosus bronchio-alveolar lavage (BAL) fluid were negative. However, tests for Aspergillus galactomannan antigen were positive. On suspicion of invasive aspergillosis the patient was prescribed antimycotic treatment with IV voriconazol 200 mg twice daily. After presentation of the case to the department of thoracic surgery, lateral thoracotomy at IC5 was performed and the cyst was removed by lobectomy of the superior lobe of the left lung. Microscopic examination and polymerase chain reaction (PCR) for DNA showed the presence of E. granulosus. Thus, the diagnosis was changed accordingly, and the patient was prescribed albendazole 400 mg, twice daily for 6 months. The patient came to regular follow-up in the outpatient clinic for infectious diseases for 12 months. The patient was asymptomatic during this period and no recurrence was observed.

PMC5854641_01

Male

A 35-year-old male, with a previous history of severe plaque-psoriasis who had started treatment with ustekinumab 4 months before, complained of progressive and persistent headache, which was refractory to non-steroidal anti-inflammatory drugs. Brain magnetic resonance imaging (MRI) was unremarkable. One year later, a new MRI was performed due to headache persistence, which revealed a homogenous and diffuse pituitary enlargement of up to 1.1 cm, which extended to the suprasellar region and contacted the optic quiasm, blurring of the pituitary stalk, absence of clear differentiation between the anterior and posterior lobes, and no signs of hemorrhage or adenomas (Figure 1). Visual fields were normal. The patient acknowledged absence of signs or symptoms suggestive of pituitary dysfunction, except for mild libido decrease and erection difficulties. Physical examination revealed multiple psoriatic plaques, with no other remarkable features. Laboratory work-up was consistent with hypogonadotropic hypogonadism, central hypothyroidism, central hypoadrenalism, and GH deficiency, but normality in the rest of the biochemical parameters evaluated (ions, proteins, lipid, renal, and hepatic profiles). Cerebrospinal fluid and work-up of infiltrative and infectious diseases, including sarcoidosis and tuberculosis, were negative. Follow-up MRI performed 6 months later revealed an increase in the pituitary enlargement to up to 1.7 cm. Because etiology of the mass was still unclear, the patient underwent transsphenoidal surgery of the sellar mass, with the purposes of both debulking and obtaining samples for biopsy. Pathological findings revealed and intense fibrosis and a chronic inflammatory infiltrate of the pituitary gland with a high proportion of lymphocytes and some plasmatic cells, but no evidence of adenoma, granuloma, or acid fast bacilli. Immunohistochemistry pointed to a combined T-cell (CD3+, CD4+, CD8+) and B-cell (CD19+, CD20+) phenotype. Additional immune analysis showed positivity for FOXP3, PD1, and IL-17, and negativity for IgG4 and S-100 protein (Figure 2). Ustekinumab was withdrawn, with subsequent improvement of headaches. Laboratory work-up after surgery revealed persistent panhypopituitarism, so hormonal replacement therapy was maintained. No other autoimmune disorders were evidenced in the clinical or analytical follow-up evaluation.

autoimmunity, hypophysitis, pituitary, psoriasis, ustekinumab

PMC4748668_01

Male

A 29-year-old man presented with complaints of fever and cough of 1 month's duration. There was no breathlessness, chest pain, hemoptysis, anorexia, or weight loss. There was no history of exposure to farm dust, metallic dust, fumes, or animal dander. The patient did not keep any pets or birds at home, and denied having any addictions. On examination, the pulse rate was 90 beats per min, respiratory rate 18 breaths per min, blood pressure 110/80 mmHg, and temperature 100 F. Pulse oximetric saturation was 98% while breathing room air. Auscultation of the chest revealed a few inspiratory crackles in both the lung bases. The rest of the physical examination was unremarkable. The complete blood count and renal function tests were normal [Table 1]. There was elevation of the liver enzymes, with normal bilirubin and alkaline phosphatase (bilirubin 0.7 mg/dL, aspartate transaminase 66 U/L, alanine transaminase 88 U/L, alkaline phosphatase 126 U/L). The coagulation profile was normal. Urine analysis was normal, and blood and urine cultures were sterile. The tuberculin skin test was positive with an induration of 13 mm. The chest radiograph showed diffusely distributed nodules in bilateral lung fields. Computed tomography of the chest showed randomly distributed tiny nodules (1-2 mm in size) in both lungs [Figure 1], with mild hepatomegaly and a few subcentimetric lymph nodes at the porta and retroperitoneum. Two possibilities were considered: Disseminated tuberculosis and sarcoidosis. Flexible bronchoscopy and TBLB, both with conventional forceps and cryoprobe, were planned. The procedure was performed in the bronchoscopy suite with local anesthesia and conscious sedation. The heart rate, oxygen saturation, blood pressure, and electrocardiogram (ECG) were monitored throughout the procedure. Continuous oxygen supplementation was provided through a face mask. The flexible bronchoscope (BF-1T180, Olympus, Tokyo, Japan) was introduced through the nose; the airway examination was normal, and subsequently, bronchoalveolar lavage was performed. TBLB was then performed using standard biopsy forceps (FB-19C, Olympus, Japan) from the basal segments of the right lower lobe. Six tissue specimens were obtained. Subsequently, cryo-TBLB was performed. The bronchoscope was introduced orally and maneuvered into the posterior segment of the right lower lobe. The flexible cryoprobe (1.9-mm outer diameter, 900-mm length, ERBE Elektromedizin, Tubingen, Germany) was introduced through the working channel of the bronchoscope into the selected segment and subsequently confirmed under fluoroscopic guidance. The probe was stationed 2 cm away from the chest wall. It was then cooled with nitrous oxide (this reduces the temperature of the probe's tip to -89 C) for 4 s. The entire bronchoscope was then retracted with the frozen lung tissue attached to the probe's tip. As soon as the bronchoscope was withdrawn from the patient, it was handed over to the technical assistant. The tip of the cryoprobe along with the first bronchoscope was immersed in normal saline at room temperature. Thawing resulted in the separation of the specimen from the tip. The specimen was then transferred into formalin. Meanwhile, the operator introduced another bronchoscope (FB-19TV, Pentax, Tokyo, Japan) immediately through the nose. Mild bleeding was visualized. The bronchoscope was immediately wedged into the posterior segment of the right lower lobe for 3 min and then withdrawn. There was no ongoing bleeding. The bronchoscope was subsequently withdrawn from the patient. Histopathological examination was done by an experienced pulmonary histopathologist. The CB was 0.5 cm in length, while the largest conventional FB specimen was 0.1 cm [Figure 2]. The surface areas of the CB and the FB were 14.18 mm2 and 1.65 mm2, respectively as measured with digital morphometry (Leica QWin version 3, Leica Microsystems Imaging Solutions Ltd, Cambridge, UK). Microscopic examination revealed 24 alveoli in FB and 212 alveoli in CB. Both the specimens revealed the presence of epithelioid cell granulomas with multiple Langhans type of giant cells and surrounding lymphocytes [Figure 3]. While there were nine granulomas in the CB, there was only one granuloma found in FB. The granuloma in the FB was a loose collection of epithelioid cells and did not have any central necrosis. The granulomas found in CB were well formed with Langhans type of giant cells and showed the presence of central necrosis with nuclear debris pointing toward a diagnosis of tuberculosis rather than sarcoidosis. There was no angiitis. Ziehl-Neelsen staining did not reveal acid-fast bacilli in either specimen. There was no artifact in the CB, while the FB showed minor crush artifacts. A diagnosis of pulmonary tuberculosis was made. The patient was started on antituberculosis treatment with oral rifampicin (600 mg), isoniazid (300 mg), pyrazinamide (1500 mg), ethambutol (1000 mg), and pyridoxine (10 mg). Fever abated in 2 weeks and cough disappeared. Chest radiograph showed reduction in the nodular opacities. Currently, at the time of writing, the patient is asymptomatic and under follow-up.

bronchoscopy, cryobiopsy, cryotherapy, lung biopsy, sarcoidosis, transbronchial lung biopsy, tuberculosis

F; Computed tomography of the chest showing multiple random nodules diffusely distributed in both the lung fields.

PMC9293051_01

Female

A 57-year-old nonsmoking woman complained of cough, shortness of breath, chest distress, dyspnea, thoracolumbar and back pain for nearly one month and presented to our center just after the end of the COVID-19 lockdowns in Wuhan. She denied a history of tuberculosis exposure and any other history of disease except for well-controlled hypertension. She was notable for apparent bilateral supraclavicular lymphadenectasis after a physical examination. A chest computed tomography (CT) scan revealed numerous uniform pulmonary nodules in the bilateral lungs in addition to a 38x45 mm mass at the dorsal segment of the lower lobe of the left lung, with bilateral hilar and mediastinal lymphadenopathy ( Figures 1A, B ), and multiple bone metastases (including thoracic spine, sternum, ribs and left scapula). The enhanced CT scans showed multiple liver (the largest nodule about 21x21mm) and adrenal metastases ( Figure 1C ). Magnetic resonance examination of the head revealed no obvious metastases ( Figure 1D ). Her laboratory results (complete blood cell count: WBC (white blood cell) 8.6x109/L, RBC (red blood cell) 4.08x109/L, PLT (platelet) 433x109/L, liver panel: ALT (alanine aminotransferase) 19U/L, AST (aspartate aminotransferase) 34U/L, kidney panel: creatinine 47mumol/L) were within normal limits, her respiratory etiology test results (including tuberculosis) were negative, but her tumor markers were elevated ( Figure 2 ). A supraclavicular lymph node biopsy was performed. Immunohistochemical staining was positive for PCK, CK7, TTF-1, and Ki-67 at 70%; negative for P40, Napsin A, Syn, and CDX-2; PD-L1(=1%, Clone: 22C3, Dako, Agilent Technologies, Inc.); which is consistent with lung adenocarcinoma ( Figure 3 ). Genetic testing of paraffin section from supraclavicular lymph node was conducted in CLIA-certified lab using hybridization capture-based next-generation sequencing panels. Gene targets (MyGene, BGI-Shenzhen [Headquarters]: Shenzhen, 518083, China. Genomic alterations assessed included single nucleotide variations, insertions and deletions, copy number variations, and gene rearrangements in selected genes. The MyGene panels covered common lung cancer-related genes. The minimum coverage across sample was >=1000x. Actionability of genomic alterations and the level of evidence were determined based on the OncoKB data set and drug approval status in mainland China ] revealed no mutated genes as EGFR [Exon 18/19/20/21/T790), FGFR2, FGFR3, ROS1, TP53, RET, PIK3CA (Exon 10/12, coding exon 9/20), ALK, KRAS (Codon 12/13/61/146), NRAS (Codon 12/13/61), KIT (Exon 9/11), BRCA1, BRCA2, and ERBB2 (Exon 20/copy number amplification). She was diagnosed with lung adenocarcinoma cT4N3M1 stage IVb, EGFR-negative (According to the eighth edition TNM classification, innumerable nodules in the ipsilateral lobes are categorized as T4, and those in a contralateral lobe while multiple metastases in distant organ are M1, bilateral hilar and mediastinal lymphadenopathy are N3). She was given a cycle of pemetrexed (day 1: 500mg/m2) and cisplatin (day 1-3: 25mg/m2 every day), but reexamination of her chest CT and abdominal CT showed no signs of a reduction in her pulmonary nodules ( Figures 1E, F ). Then, three cycles of sintilimab (PD-1 inhibitor, day 1: 200mg) plus pemetrexed (day 1: 500mg/m2) and cisplatin (day 1-3: 25mg/m2 every day) were administered, the patient suffered greatly thoracolumbar and back pain, fierce cough, wheezing, chest distress, and dyspnea. Although there were no other immune-related adverse events, the treatment was terminated because of persistent disease progression ( Figures 1G, H ). Then, the patient received two cycles of recombinant human endostatin (Endostar, day 1-14: 7.5mg/m2 every day) combined with docetaxel (day 1: 75mg/m2) and lobaplatin (day 1: 75mg/m2). Her white blood cells were normal, liver and kidney function tests were normal (WBC 5.4x109/L, RBC 3.53x109/L, PLT 313x109/L, ALT 25U/L, AST 33U/L, creatinine 39mumol/L). Her symptoms, including cough, shortness of breath, wheezing, chest distress, dyspnea, thoracolumbar and back pain, were significantly relieved. She had no drug-related symptoms other than mild itching on his skin during this treatment period. Fortunately, chest and abdomen CT scans revealed almost complete disappearance of all pulmonary nodules, as well as an accentuated decrease in the primary lung mass (32x32mm) and liver metastasis volume (the largest one about 16x15mm) after this two cycle's treatment ( Figures 1I-L ). The diagram of her specific treatment progress see Figure 1 .

anti-angiogenic therapy, immunotherapy, lung adenocarcinoma, miliary metastasis, recombinant human endostatin

PMC4735024_01

Female

Vulval and vaginal TB presented extensive painful genital ulcers, even in a sexually inactive pubertal girl. Tiwari et al. reported a case of hypertrophic vulval TB of primary origin in a 26-year-old female patient. The diagnosis was mainly based on histopathological examination.

bladder, cancer, extrapulmonary, female, genital, male, penis, prostate, tuberculosis, ureter, urethra, urogenital, vulva

PMC4735024_02

Female

A case of tubo-ovarian TB mimicking acute appendicitis was described by Akbulut et al.. A 17-year-old woman presented with complaints of right lower quadrant abdominal pain, nausea, and vomiting; acute appendicitis was diagnosed. A cystic mass was detected on the right tubo-ovarian structure by laparotomy and was excised: TB was found by histology.

bladder, cancer, extrapulmonary, female, genital, male, penis, prostate, tuberculosis, ureter, urethra, urogenital, vulva

PMC4735024_03

Female

The same case Ilmer et al. have presented. A 35-year-old human immunodeficiency virus seropositive woman complained of lower abdominal pain and fever for two days. She underwent surgery due to left adnexal mass suggesting pelvic inflammatory disease. The peritonitis provoked by a tubo-ovarian abscess on the left side was found. Histopathological evaluation identified TB salpingitis and Mtb was found by polymerase chain reaction (PCR).

bladder, cancer, extrapulmonary, female, genital, male, penis, prostate, tuberculosis, ureter, urethra, urogenital, vulva

PMC4735024_04

Female

Our first case demonstrates a typical scenario of FGTB. A 29 years-old woman presented with a history of 11 years infertility and of Trichomonas vaginalis and Chlamydia trachomatis infections last year. She had no fever or weight loss. She had no past or family history of TB. Her pelvic ultrasound examination revealed paraovarian cysts near fallopian tubes. The size of left cyst was 18.7 mm x 9.9 mm, right cyst was 16.7 mm x 12.2 mm. The patient underwent laparoscopy, and extensive changes in the ampullary region of both tubes were found (Fig. 1, Fig. 2, Fig. 3). The uterus was displaced to the left because of the peritoneal adhesions in the Douglas's Pouch (Fig. 4). Histology revealed the cicatricial and adherent form of FGTB. Mtb was found in the tubal samples by PCR. Two cases of congenital TB were reported by Das et al.. Case one presented at 12 days of age. The mother had been symptomatic for TB in the first trimester but was not diagnosed until her infant developed symptoms. The infant's gastric aspirate was acid-fast-bacilli (AFB)-positive and Mtb - culture-positive. PCR on the gastric specimen and mother's sputum demonstrated identical strains. Case two presented at 45 days of age and the gastric aspirate was both AFB- and culture-positive. The mother was asymptomatic and contact-tracing of the family failed to detect infection. However, FGTB was found on an endometrial biopsy. Agrawal et al. described the case of a male preterm baby who had congenital miliary TB with multiple intestinal perforations. Exacerbation of latent genital TB during in vitro fertilization and pregnancy was described by Huang et al..

bladder, cancer, extrapulmonary, female, genital, male, penis, prostate, tuberculosis, ureter, urethra, urogenital, vulva

PMC4735024_05

Female

Dadhwal et al. reported a case of TB flare in a 28-year-old nulliparous woman following endometrial aspiration, which drained 30 ml pus. Following this, high-grade fever and pain in abdomen with rigidity had appeared. PCR was positive for Mtb and histopathology showed necrotizing TB endometritis. She also showed features of chronic TB meningitis. Our second case demonstrates an extremely rare case of TB of placenta in young woman, suffered from genital TB, which was overlooked before delivery. This woman had no any contact with TB infection, had no history of TB, had no any complaints before pregnancy and had no special complaints during her pregnancy. The delivery was normal with healthy baby. In Russian Federation the investigation of the placenta is standard approach, and TB inflammation (Fig. 5) and Mtb in the placenta (Fig. 6) were surprisingly revealed. This woman got sick with TB in time of pregnancy - but her organism mobilized all reserves and localized TB inflammation in placenta only; the baby left well. In 3 months the calcification was found in the left ovary that was estimated as a sign of mother's self-recovery.

bladder, cancer, extrapulmonary, female, genital, male, penis, prostate, tuberculosis, ureter, urethra, urogenital, vulva

PMC7569747_01

Female

A 33 year old Newar housewife from Kathmandu, Nepal, with no known comorbidity, presented to Patan Hospital Emergency Department in November, 2019 with a history of cough with occasional sputum production over the previous 20 days and low grade fever for 10 days. There was no history of chest pain, difficulty breathing, headache, vomiting, altered mentation, abdominal pain, yellowish discoloration of eyes, burning urine, hair loss, photosensitivity, joint pain, or rash but she had decreased appetite and weight loss. There was no past history of tuberculosis or jaundice. She did not consume alcohol or any drugs including acetaminophen, aflatoxin or herbal products. Her father-in-law had been diagnosed with pulmonary tuberculosis five years earlier, but there was no family history of liver disease. Initial examination showed temperature of 101 oF with pulse of 110 beats/minute and respiratory rate of 26 breaths/minute. There was diffuse fine crepitation on the left side on auscultation of the chest. There was no lymphadenopathy, icterus, peripheral edema or wheezes. Neck veins were not distended. Liver and spleen were not palpable, and abdomen examination was normal. Laboratory parameters with normal ranges in parenthesis are as follow: Complete blood count before transfusion: white cell count 7.8 (4-10) x 10 9/L; neutrophils 80%; lymphocytes 16%; monocytes 4%; red blood cells 3.6 (4.2-5.4) x 10 12/L; haemoglobin 10.6 (12-15) g/dL; platelets 410 (150-400) x 10 9/L. Biochemistry: random blood sugar 126 (65-110) mg/dL; urea 39 (17-45) mg/dL; creatinine 1.1 (0.8-1.3) mg/dL; sodium 138 (135-145) mmol/L and potassium 4 (3.5-5) mmol/L. Chest X-ray ( Figure 1) showed thick walled cavitating lesions in the left upper lobe and patchy infiltrates in left middle and lower zones. There were hyperinflated lung fields with blunting of left costophrenic angle. Sputum smear examination showed 3+ acid fast bacilli. Sputum Gene Xpert was positive for Rifampicin sensitive tubercle bacilli. A diagnosis of pulmonary tuberculosis was made, and planned for starting ATT. Liver function test was performed as baseline workup before starting treatment which showed the following results (with normal ranges in parenthesis): bilirubin total 1.1 (0.1-1.2) mg/dL and direct 0.5 (0-0.4) mg/dL; alanine transaminase 308 (5-30) units/L; aspartate transaminase 605 (5-30) units/L; alkaline phosphatase 149 (50-100) IU/L; gamma-glutamyltranspeptidase66 (9-48) units/L. The raised transaminases led us to perform further workup for liver disease. There was no clinical evidence of chronic liver disease or portal hypertension. Liver synthetic functions were as following;albumin 3.5 (3.5-5) g/dL; total protein 6.5 (6-8.3) g/dL; prothrombin time 14 (11-13.5) s. Serologies for HIV, HBsAg, Hepatitis C virus (HCV), Hepatitis A virus (HAV) and Hepatitis E virus (HEV) were nonreactive. Testing for other hepatotropic viruses was not done because of unavailability of the tests. Neurological examinations and the slit lamp examination of eye were normal. Ultrasound of the abdomen showed a normal sized liver with smooth outline and echotexture. However fibroscan, upper gastrointestinal endoscopy, abdominal CT scan and liver biopsy were not done due to financial constraints of the patient. She was admitted to the respiratory isolation unit. At first there was some hesitation in starting the full treatment for her pulmonary tuberculosis because of her liver function tests. But taking into consideration her presentation and laboratory findings, we opted for the full treatment rather than a modified TB regimen. We started standard four drugs ATT based on her weight as per national TB guidelines which included three tablets of HRZE given once daily with each tablet containing 75 mg isoniazid (H), 150 mg rifampicin (R), 400 mg pyrazinamide (Z) and 275 mg ethambutol (E). This led to improvement in her clinical status. She was closely observed for possible worsening of her liver disease due to the hepatotoxic antitubercular drugs. Providentially, at 1 week after starting treatment, she was afebrile and continuing to improve and her liver function test showed a total bilirubin of 0.7 mg/dl, aspartate transaminase of 40 IU/L and alanine transaminase of 62 IU/L. She was discharged with advice to follow up in 1 month. At 1 month follow up she had no symptoms and therefore no further tests were done. At 2 months, she was still asymptomatic and her sputum smear was negative for acid fast bacilli. Her liver function test showed a total bilirubin of 0.6 mg/dl, aspartate transaminase of 30 IU/L and alanine transaminase of 35 IU/L. She was switched to3 tablets of HR to be taken for 4 months.

liver friendly regimen, standard att, transaminitis, tuberculosis

PMC8240889_01

Male

A 15-year-old male with a history of multiple, unreported football-related headaches, described feeling "out of it" at the beginning of a high school football game during his junior year. Through the first half of the game, he sustained multiple collisions with other players and an episode of head-to-ground contact. At halftime, the athlete struggled to recall routine stretching exercises and reported difficulty with concentration, dizziness, disorientation, and nausea. During his initial sideline assessment, approximately 25 min after the last contact play, he lost consciousness and sustained a 3- to 4-min generalized tonic-clonic seizure with left hemiparesis in the initial post-ictal period. He spontaneously regained consciousness and was transported to the nearest emergency department, where non-contrast computerized tomography (CT) of the head and neck were unremarkable for acute fracture, intracranial hemorrhage, or edema. He was diagnosed with a concussion and instructed to follow up as an outpatient. Two days after the event, the patient completed an initial symptom severity inventory and underwent a complete history and physical exam. His symptoms included mild to moderate headaches, dizziness, nausea, fatigue, visual problems, noise sensitivity, light sensitivity, difficulty concentrating, irritability, difficulty remembering, drowsiness, trouble falling asleep, and sleeping more than usual. Past medical history was unremarkable with the exception of multiple, unreported football-related head injuries that resulted in symptoms consistent with SRC, although he was never formally evaluated for these injuries. His physical exam was notable for a positive Spurling test on the right, pain-limiting range of motion in the cervical spine, and left occipital tenderness. The patient did not display any objective signs of dysmetria, weakness, or cranial nerve deficits. He was diagnosed with a cervical spine sprain, concussion with loss of consciousness, and post-concussive seizure. Treatment included academic modifications, a low-intensity heart rate-controlled home exercise program, proper sleep hygiene, and avoidance of contact sports. At follow-up 2 weeks later, the patient's symptom severity decreased compared with his initial survey results and he continued with the same treatment regimen. The patient had persistent post-concussion symptoms and had a witnessed tonic-clonic seizure after neuropsychological testing 10 weeks after injury. He experienced two more unprovoked tonic-clonic seizures in the first 4 months post-injury. Magnetic resonance imaging (MRI) of the brain without contrast did not reveal focal abnormality and electroencephalography (EEG) demonstrated right greater than left temporal slowing and right temporal, sharp waves. He began oxcarbazepine therapy and was followed closely by a sports physician, neurologist, neuropsychologist, cognitive behavioral therapist, physical therapist, athletic trainer, and neuroopthalmologist. His symptoms slowly improved over time and he had one seizure event since starting antiepileptic medication. One year after the event, he continues to experience mild, but improved post-concussive symptoms.

brain injury, concussion, post-traumatic epilepsy, sports-related concussion

PMC4428364_01

Female

A 44-year-old woman of Turkish origin presented to the emergency department with severe dyspnea and inspiratory pleural chest pain that had developed over the previous few days. She had delivered healthy twins 6 weeks prior to presentation and had been diagnosed with a pulmonary embolism 3 months previously. She had never smoked. Her past medical history revealed a diagnosis of COPD that had been made 9 years earlier during her pregnancy with her first child, at which time she became symptomatic for the first time. There was no family history of respiratory or liver disease. She had no history of childhood asthma or allergies. Her current medication consisted of subcutaneous tinzaparin, a low molecular weight heparin, for pulmonary embolism, and inhaled tiotropium, formoterol, and budesonide. Initial laboratory workup showed a leukocytosis of 12.6 g/L (normal range 6-11 g/L), mildly elevated C-reactive protein of 2.6 (normal range <0.5) and thrombocytosis of 485 g/L (normal range 150-400 g/L). Differential white blood cells showed an eosinophilia of 7% (normal <4%). Blood gas analysis showed severe respiratory insufficiency (paO2 54 mmHg, paCO2 38 mmHg). A chest computed tomography scan revealed very severe bronchiectasis with large cysts and mucus plugging, predominantly in the lower lung segments, suggestive of cystic fibrosis (Figure 1). Additionally, ground glass opacities were noted in the upper lung segments and infiltrates in the right middle lobe. Marked emphysema was not present, and no residual thrombi were seen in the pulmonary arteries. Upon echocardiography, right and left heart function were normal and her brain natriuretic peptide level was normal. Lung function analysis showed severe obstruction (forced expiratory volume in 1 second [FEV1] 1,06 L/43%, FEV1/vital capacity 47%) and moderate relative hyperinflation (residual volume 2.2 L/140%, total lung capacity 4.37 L/99%). Sputum analysis revealed mucoid Pseudomonas aeruginosa and Aspergillus fumigatus. Mycobacterial infection was excluded by repeated sputum analysis, including polymerase chain reaction. An interferon-gamma release assay for tuberculosis antigen-specific T-cell response was negative. Bronchiectasis workup, including immunoglobulin (Ig)A, IgM, IgG, and subclasses, was normal. Total IgE levels were increased to 584 IU/mL (normal <100 IU/mL) and specific IgG and IgE were high for A. fumigatus (IgG 106 mgA/I; low range <14 mgA/I, intermediate range 14-39 mgA/I; high range >39 mgA/I; IgE 46 IU/mL, FEIA class 4), indicative of possible allergic bronchopulmonary aspergillosis (ABPA). Prick testing against common environmental antigens, such as pollen, house dust mite, and animal hair, was negative. An antinuclear antibody titer of 1:100 was noted, but extractable nuclear antigen screening (RNP/Sm, Sm, SS-A, SS-B, Scl70, CentB, Ho-1, Rib-P) was unremarkable. Antineutrophil cytoplasmic antibody (ANCA) testing was negative. A thrombophilia screen, including factor V Leiden, prothrombin gene mutation, antithrombin 3, proteins C and S, and lupus anticoagulant had been performed at the time of diagnosis and had revealed no abnormalities. Sweat chloride testing was normal (<25 mM) and no CFTR gene mutation was found. Capillary zone electrophoresis indicated a marked decrease in alpha-1 globin band 0.18 g/dL, 2.6% (Figure 2). The AAT level in serum was below 25 mg/dL (measured by the Cobas C702 nephelometry kit, Roche, Basel, Switzerland; quantification range 25-600 mg/dL, detection limit 10 mg/dL). Upon genetic testing, no S or Z mutations were found in the sequencing of exon 3 or exon 5 of the SERPINA-1 gene. Further sequencing analysis of all exons of the SERPINA-1 gene revealed a homozygous CA insertion in exon 2, leading to a frame shift starting at codon 73. This mutation probably leads to a dysfunctional truncated protein lacking the reactive center loop (Figure 3). There was no suggestion of liver disease on sonography and liver enzymes (alanine transaminase, aspartate transaminase, gamma-glutamyl transpeptidase, alkaline phosphatase) were normal. There was no apparent skin disease. The patient was treated with oxygen therapy, oral ciprofloxacin, and inhaled colistin twice daily for P. aeruginosa infection. Later, itraconazole and prednisolone were added for treatment of probable ABPA.

serpina-1 mutation, alpha-1 antitrypsin deficiency, bronchiectasis, pulmonary embolism

PMC3425226_01

Female

A 67-year-old female presented with dysphagia and loss of weight. There was no lymphadenopathy. She denied any history of previous tuberculosis. On palpation, abdomen was soft and nontender without organomegaly. Ultrasound of the abdomen and computed tomography (CT) showed revealed diffuse thickening of the stomach. Additionally, specks of calcification were noted in the gastric wall on CT. Gastric endoscopy was normal and endoscopic biopsy was negative for malignancy. With suspicion of gastric lymphoma, she was subjected to [18F] fluoro-deoxy-glucose (FDG) positron emission tomography (PET). Whole body contrast-enhanced PET/CT was performed 1 hour after intravenous injection of 10 mCi of F-18 FDG. It showed [Figure 1] diffusely thickened gastric wall with few specks of calcification with intense FDG uptake in the thickened gastric wall (SUVmax 8.3). No significant lymphadenopathy was noted. No abnormal FDG uptake was noted in rest of the organs. The patient was subsequently subjected to laparotomy due to high risk of malignancy. Intraoperatively diffuse thickening of the gastric wall was noted and was inoperable. Biopsy revealed diffuse infiltration of the gastric wall by signet cell adenocarcinoma. The patient is being treated with chemotherapy.

f-18 fdg, pet/ct, linitis plastica, stomach cancer

PMC8129905_01

Male

An 86-year-old male presented to the hospital with hypotension, chronic left shoulder pain, and an associated effusion in 2014. Remotely, he had undergone left shoulder acromioplasty, followed by hemiarthroplasty in 2010, for severe rotator cuff arthropathy. In 2012, he developed pain at the site of the left shoulder after a fall. Shoulder radiographs showed a stable hemiarthroplasty without evidence of complication. The shoulder pain persisted, and he gradually developed swelling over the left shoulder joint. In 2013, computed tomography (CT) of the shoulder showed a lytic destructive process involving the scapula associated with a large extra-articular proliferative soft tissue process centered on the glenohumeral joint. The mass measured cm and contained internal calcifications (Fig. 1a). Lysis and fragmentation of adjacent bony structures (especially the acromion) were noted. A neoplastic process such as chondrosarcoma was suspected. A subsequent CT-guided biopsy of the left clavicle lytic lesion was nondiagnostic. Four months prior to admission, the patient underwent a second, open biopsy of the left shoulder mass and distal clavicle. Bacterial cultures were negative. No fungal or mycobacterial cultures were obtained. Pathology from the clavicle demonstrated multiple non-necrotizing granulomata. Special stains on the formalin-fixed tissues were negative for fungal and mycobacteria organisms. The past medical history included diabetes complicated by retinopathy, atrial fibrillation, diastolic heart failure, stage III chronic kidney disease, chronic obstructive pulmonary disease, penicillin allergy, and previously treated bladder cancer. On examination, a draining sinus tract over the left deltoid was noted. The tract had appeared after the open biopsy 4 months previously. A radiograph of the left shoulder demonstrated erosive changes and extensive demineralization of the left proximal humerus with left shoulder arthroplasty hardware in place (Fig. 1b), erosion and separation of the acromioclavicular joint, ossific debris in the subacromial-subdeltoid bursa, and destruction of the glenoid. The findings were felt to be consistent with hardware-associated osteomyelitis. Inflammatory markers were elevated (C-reactive protein 19.5 mg/dL; erythrocyte sedimentation rate 46 mm/h). Bacterial culture of sinus tract fluid yielded Proteus mirabilis. The patient was taken to the OR for hemiarthroplasty removal, biopsy of the distal clavicle, and placement of an antibiotic-impregnated cement spacer. Four days later, he underwent a second irrigation and drainage, at which time the spacer was removed. Pathology on the resected bone revealed granulomas. Operative samples grew Peptostreptococcus. Fungal cultures were negative. No mycobacterial cultures were obtained. He received intravenous clindamycin and aztreonam for approximately 6 weeks, with minimal change in symptoms or inflammatory markers. Subsequently, he was treated with vacuum-assisted wound closure and required several additional washouts for bleeding into the shoulder joint space, along with intermittent courses of oral and IV antibiotic therapy. Eighteen months after arthroplasty removal, the patient was readmitted to the hospital with persistent left shoulder pain and effusion, 38 kg weight loss, and malaise. A radiograph of the left shoulder revealed erosion of the left proximal humerus at the site of explanted arthroplasty hardware, along with other findings highly suspicious for osteomyelitis and septic arthritis of the proximal humerus and acromioclavicular joint (Fig. 2a). Magnetic resonance imaging (MRI) demonstrated a peripherally enhancing glenohumeral joint effusion and intra-humeral abscess (Fig. 2b). An aspirate of synovial fluid containing 7000 white cells/mm (76 % neutrophils) was pan-cultured. Cutibacterium acnes and a Kocuria species were recovered from bacterial culture. After 18 d, growth from the mycobacterial cultures of the shoulder joint aspirate was observed; the organism was identified as the Mycobacterium tuberculosis (MTb) complex by a commercial DNA probe assay. The patient's QuantiFERON -TB Gold blood test was negative. Chest imaging showed no evidence of tuberculosis in the lungs, pleura, or lymph nodes. Sputum samples were submitted for acid fast stain and culture, both of which were negative. Abdominal CT imaging revealed cirrhosis and ascites, previously undiagnosed. Resistance testing to all first-line anti-mycobacterial drugs was requested, and preliminary results were reported 27 d after cultures became positive (final results were available 42 d after culture positivity). The isolate was susceptible to isoniazid, rifampin, and ethambutol but resistant to pyrazinamide. These results raised suspicion for infection due to M. bovis, a member of the MTb complex, which is intrinsically resistant to pyrazinamide. Using spacer oligonucleotide typing (spoligotyping) and analysis of mycobacterial interspersed repetitive units (MIRU), the isolate was subsequently confirmed to be the BCG strain of M. bovis. Detailed review of the patient's medical history revealed that he had been treated for urothelial carcinoma with transurethral bladder resection and BCG therapy in 1996. In 2012, the bladder cancer had recurred and was treated with a second course of BCG, which was complicated by persistent cystitis and bladder ulcerations. A liver-sparing anti-tuberculosis regimen (rifampin, ethambutol, and levofloxacin) was initiated, which the patient tolerated well. However, because of his symptoms of cachexia and weakness, he elected to enter hospice care. All anti-mycobacterial drugs were discontinued, and he expired 13 d after hospital discharge.

PMC8579051_01

Male

A case of a 18-year-old male student having suffered from headache and visual impairments for about two months is reported. Neurological examination was negative. CT-scan performed in urgency revealed the presence of triventricular hydrocephalus caused by stenosis of the cerebral aqueduct. The most urgent therapeutic goal was mainly the management of the hydrocephalus, therefore a ventricular-peritoneal shunt placement (Medos Hakin-programmable valve) was used to provide an alternative flow pathway for the cerebrospinal fluid. The critical location of the lesion discouraged the STB procedure to obtain histopathological specimens available for the diagnosis. In addition, biochemical analysis of cerebrospinal liquor resulted normal with regard to cell count and protein content. Flow chart adopted in the diagnostic phase is reported in Figure 1 . Post-shunting (20 days) MRI showed a significant decrease of the ventricular size. Moreover, the MRI revealed a nodular lesion within the mesencephalic tectum with hypo-intense areas on the T1-weighted images ( Figure 2A ) and hyper intense signals on the T2-weighted sequence ( Figure 2B ). Gadolinium- T1-weighted image showed a low focal enhancement of the lesion in the periaqueductal area which suggested a reduced damage of the blood-brain barrier ( Figure 2C ). Proton magnetic resonance spectroscopy (H-MRS) revealed elevated choline peaks (choline/creatinine ratio at 1,9) in addition to reduced NAA (N-acetylaspartate) ( Figure 2D ). The perfusion-weighted imaging (PWI) of the lesion showed a low value of relative cerebral blood volume (CBV) ( Figure 2E ). The MR signal alteration was non-specific and could suggest, as alternative diagnostic hypothesis to a neoplasm, inflammatory lesions of various types, demyelinating and vascular. The impossibility, given the mesencephalic location of the lesion, to perform a STB confirms the importance of the information which could be obtained with the cytological observation of peripheral blood CTCs shortly cultured in vitro and obtained applying a protocol previously described. Biomolecular pathways and cell culture plays a pivotal role in cancer research. However, culture-induced changes in biological properties of tumor cells might profoundly affect research reproducibility and translational potential. For this reason, the cytological preparations we used in this diagnostic procedure were prepared with a protocol of short-time in vitro expansion, which we have widely shown to maintain phenotypic and genotypic features of CTCs. The volume of the starting blood sample was 5 ml. Briefly, adensity gradient was applied to the blood sample. The cellular suspension isolated in correspondence of the working density phase ( Figures 3a, b ) was seeded on chamber slides ( Figure 3d ) for a short-time expansion of 14 days. The procedure of expansion had two objectives: i) to unmask rare non-haematological cells with atypical proliferation ability in vitro and ii) to highlight rare cells numerically sufficient and viable for further characterization. After 14 days, the adherent cells were fixed and stained for cytological examination. The culture density of CTCs in the total cultivated cells was of 1:50. The lower rate of atypical cells in the blood-derived culture suggested finding these elements directly in peripheral blood difficult. In fact, the analysis for the presence of negative CD45 cells (CD45 is a marker of the haematological population) was negative in the patient's whole blood sample. In this case, as shown in Figure 3 , the Hematoxylin and Eosin (H&E) stained cytological preparations revealed the presence of bulky, polinucleated or spindled cell atypical elements ( Figures 3A, B ). In addition, these atypical cells found in the blood resulted, at the immunohistochemical analysis performed through methods previously described, positive for the expression of the astrocytes markers S-100 ( Figures 3C, D ) and glial fibrillary acidic protein (GFAP) ( Figures 3E, F ). A section of brain human tissue was used as internal positive control. Moreover, as negative control, demonstrating that the reaction visualized is due to the interaction of the epitope of the target molecule and the paratope of the antibody/affinity reagent, parallel assays with the primary antibodies omitted was performed. Moreover, as positive control for the presence of CTCs from cerebral lesions in the peripheral blood we used cytological preparations obtained with the same method from peripheral blood collected from one case of glioblastoma and from one case of brain metastasis from melanoma (cerebral metastasis) ( Figures 3G, H ). As negative control was used the cytological pattern isolated by peripheral blood collected from a case of post-stroke frontal lobe scar ( Figure 3I ). The final cytological diagnosis was of pilocytic astrocytoma because the protean features of the proliferating glial elements ( Figures 3A-F ). The control MRI (6 months after shunt placement) documented that the lesion was stable. Moreover, the area of altered signal at the quadrigeminal plate, hyperintense on T2/Fluid Attenuation Inversion Recovery (FLAIR), hypointense on T1-weighted images, placed at the entrance of the aqueduct of Sylvius, decreased in width. MRI was repeated evert 6 months in the first 2 years; afterwards, an annual MRI was performed, without changes in the radiological picture. Clinical outcome (68 months) supported by follow up corroborates the pathological diagnosis of pilocytic astrocytoma/low grade glioma. The patient provided written consent in accordance with ethical principles, relevant guidelines and regulations of the Declaration of Helsinki in accordance with experimental protocols included in the study approved by the local ethical committee, with study number 2013.34. The consent includes also authorization to publish the collected data for medical/scientific purposes in accordance with local laws.

blood brain barrier, brain tumors, circulating glial cells, diagnostic liquid biopsy, pilocytic astrocytoma

PMC5329821_01

Male

On July 8th, 2014, a 37-year-old male was admitted to our departmentwith persistent cough for two years, and chest distress and fatigue for more than one year. He felt progressive dyspnea after activity, but no wheezing, joint changes, chest pain or rash in the previous 2 years. Confuingly, he had developed left pneumothorax twice (in May 2013 and June 2014) without any injury, and recovered after thoracic drainage. The doctor arranged an X-ray but not thoracic Computed Tomography (CT) for him when the first pneumothorax occurred. After the first pneumothorax episode, the patient gradually felt the onset of chest distress, dyspnea and fatigue. Unfortunately, the patient was not diagnosed with disease until after the second pneumothorax episode on June 9th 2014. According to the thoracic CT done in June 2014, there are only find bilateral pulmonary diffuse changes with panlobular emphysema. He was diagnosed with pulmonary emphysema. The patient's local doctors suggested the patient stop smoking and prescribed montelukast. Half of a month later, the patient continued to have chest distress and dyspnea, especially post-activity. The patient came to the Department of Respiratory Medicine at the First Affiliated Hospital of Zhejiang for help. He had no previous history of Hepatitis, tuberculosis, diabetes or hypertension. He had previously smoked for 10 years, and had a smoking index of 200 (smoking cessation less than 2 months). He works as a clerk, denied alcohol addiction, and has no special gas and toxic substance exposure history. His wife and his son are healthy. On examination, his temperature was 36.9 C, his blood pressure was 121/82 mmHg, his pulse 70 beats per minute, his respiratory rate was 19 beats per minute and his oxygen saturation was 97% without oxygen inhalation. There was no cyanosis, no distension of jugular vein and no clubbing. The trachea position was normal, and there was normal breath movement and sound with no crackle. There was no lower extremity edema. The remainder of the examination was normal. Blood gas analysis showed PaO2 76.7 mmHg,PaCO2 44.2 mmHg, SPO2 95.7%,HCO3-24.9 mmol/L,and BE-0.2 mmol/L. Liver and renal function tests were normal, as were blood levels of glucose, calcium, total protein, albumin and globulin. White cell count, hemoglobin and platelet count were normal. Anti-Nuclear Antibody (ANA) and Anti-Neutrophil Cytoplasmic Antibodies (ANCA) were normal. Thyroid Function, erythrocytesedimentationrate (ESR) and immunoglobulin were normal. The thoracic HRCT done on 08-July-2015 showed a bilateral diffuse cyst, especially in upper lobe and middle lobe (Figure 1). Magnetic Resonance Imaging (MRI) of the hypophysis was normal. Cardiac and abdominal ultrasounds were normal. Lung function (assessed on 08-July-2014) was FVC 1.22L (28.1% pred), FEV1 0.48L (13.8% pred), FVC/FEV1 (39.8% pred), TCL 5.60L (89.4% pred), RV 3.26L (186.3% pred), RV/TCL 208% pred, and DLCO (30.5%pred). The results of the lung function tests showed severe obstruction of mixed ventilation dysfunction and severe diffusion dysfunction. After admittance, our initial diagnosis was Bilateral Pulmonary Diffuse Change, potentially with PLCH. To diagnose the patient definitively, we conducted bronchoscopy and video-assisted thoracicscopic surgery. The bronchoscopy did not find neoplasms or the other abnormal lesions except bilateral mucus congestion. During the bronchoscopy, we collected bronchoalveolar lavage (BAL) and analyzed the cell differential. The Left lingual BAL showed: Macrophage 23%, Neutrophil 57%, Lymphocyte 11% and Eosinophil's 9%. The Right Middle Lobe (RML) BAL showed: Macrophage 84%, Neutrophil 5%, Lymphocyte 10% and Eosinophil's 1%. A diagnosis could not be made from the BAL results due to a lack of CD1a expression. The patient was consented for Video-Assisted Thoacoscopic Surgery (VATS) for a biopsy to assist in making a diagnosis. Histopathology of the biopsy showed inflammatory cell infiltration in the left upper lobe and fiber-vessel proliferation (Figure 2). The specimen pathology showed a section of lung tissue with a honeycomb appearance. Microscopic pathology showed alveolar atrophy, island-like fibroplasia and inflammatory cell infiltration. The immunohistochemistry (IHC) results were P53 (-), Ki-67 (-), Des (-), CD34 (+), S-100 (-), CD1a(-), TTF-1 (+),SMA (+), CK7 (+), CD34 (-), CD68 (-), CD163 (-), CD31 (+), CD14 (+) and Masson (+). The final pathology report diagnosed smoking-related interstitial lung disease, but could not distinguish the definite kind. After the biopsy, we consulted with Professor FanQing Meng, a pathologist at Nanjing Drum Tower Hospital. Professor Meng agreed with our pathologist's assessment. Ethical approval: The research related to human use has been complied with all the relevant national regulations, institutional policies and in accordance the tenets of the Helsinki Declaration, and has been approved by the authors' institutional review board or equivalent committee. Informed consent: Informed consent has been obtained from all individuals included in this study. After discharge from hospital, the patient stopped smoking and only use Spiriva when needed to dilate the bronchia. Two months later, the patient returned to clinic to have his lung function evaluated and a thoracic HRCT. He felt better than he had the previous July; he could walk a little faster than before and climb 2 floors of stairs. His lung function showed improvement (Table 1). We prescribed Spiriva and advised him to use unceasingly. We followed up the patient by phone 6 months after his discharge from hospital. He reported that he took Spiriva everyday and felt better and back to normal. The patient refused to return to the First Affiliated Hospital of Zhejiang as it is a far distance from his home. After 1 year, we called him again. He had already returned to work with a reduced work load. He continued to take Spiriva. He again refused to return to the hospital for further follow up. We suggested him to continue not smoking and taking Spiriva. He accepted. Two months after the patient was discharged from the hospital, we consulted Professor Ulrich Costabel, the world-famous expert in ILD, about the case and diagnosis. Prof. Costabel diagnosed PLCH from the patient's recurrent pneumothorax and the other clinical manifestation, HRCT, follow-up presentation after smoking cessation and using Spiriva.

interstitial lung disease, pulmonary langerhans cell histiocytosis, sr-ild, smoking-related interstial lung disease, spiriva, tiotropium

PMC7501745_02

Female

Polioviruses; wild and vaccine-derived, have been reported more in the northern states compared to the southern part of Nigeria with a record of active immunisation activities. The present case of VDPV in a southern state was the first of its kind to our knowledge, being a female and a one-month-day-old child. Majority of cases in the previous outbreaks were male children with an average age of two years. Poliomyelitis is a disease of children, but all ages can be affected and there is no sex predilection. The clinical and epidemiological characteristics of the case reported are consistent with what was reported in the literature. Available clinical data from this report showed that the confirmed case had various symptoms, including the inability to move the affected limbs, fever and severe pains in the intestine, with the case ending up being dead. This finding is consistent with previous reports of cVDPV1 and cVDPV2 infections, for which a cumulative 74% of cVDPV-associated AFP cases involved residual paralysis and fever typical of poliomyelitis. However, outcome data are not usually reported with the outbreaks. The final classification of the virus is still in doubt and we recognised this as a limitation of our investigation. The laboratory report we have access to did not provide the gene bank assession number as well as the serotype of the virus. If we consider that it is an iVDPV, the immunological status of the infant is not documented regarding immune pathologies or immune deficiencies and no blood sample was collected for testing blood immunoglobulins (Ig) levels. WHO recommends clinical and biological investigations, including diagnosis of immune deficiencies before classifying a VDPV as iVDPV. More so, the vaccination profile of the case indicated that she was adequately vaccinated for her age, although she did not receive any dose of OPV during SIAs. Furthermore, there was no evidence of person-to-person transmission in the community to classify it as cVDPV. The outcome of the investigation on vaccination coverage conducted among the under-five children in the immediate environment of the case revealed that majority of them were vaccinated both in the last SIAs round and the round before it. Different from this report, earlier authors have attributed under-vaccination among children with the emergence of poliovirus infection. For instance, Kamadjeu et al. observed that 55% of all WPV cases had never received OPV (so-called zero-dose individuals) and almost 80% were under-vaccinated (i.e. they received <=3 doses of OPV) in Somalia. In addition, most patients with cVDPV2 and WPV were under-vaccinated in Nigeria. However, at the population level, the record of administrative OPV coverage in the LGA in the last four years revealed a drop in RI from 94% in 2012, 83% in 2013, 103% in 2014 to 67% in 2015. This drop in coverage rate, if it is real, may have contributed to the re-emergence of the infection in the LGA which indicated a population immunity gap that enables the development of the poliovirus. This finding alone is in accord with previous studies suggesting that the principal risk factor for VDPV emergence and spread is low population immunity. Other authors reached similar conclusions using NP-AFP and NICS 2006 data to estimate coverage with type 2-containing OPV. Moreover, asides the drop in the RI in the affected LGA, the environmental characteristics of the case-patient may also contribute towards the emergence of the infection. We observed that the case had lived in a filthy environment with poor toilet and water facilities, which could aid the occurrence of the infection. Similar observations were also made in earlier reports. The immunisation response administrative data revealed that a substantial number of children were vaccinated in the affected ward while more than 100% coverage rates were achieved during the three rounds of the large-scale response in the states where they were conducted. It is expected that this will boost the herd immunity and prevent transmission. A similar response has been conducted in previous outbreaks in Nigeria with an encouraging outcome. For instance, after two rounds of tOPV SIAs conducted in affected northern states in Nigeria in May and August 2009, monthly incidence of cVDPV2 decreased sharply from 35 cases in 2009 to 0-3 cases during September 2009-June 2010. The SIAs, being a mass vaccination campaign strategy aimed to administer additional doses of oral poliovirus vaccine (OPV) to each child aged <5 years, regardless of their vaccination history, may have proven effective in reducing the incidence of VDPV. The strategy has also been mainly used in many countries and has contributed to the 99% global reduction in the incidence of paralytic poliomyelitis observed since 1988 lunch of the global polio eradication initiative. We identified some crucial strengths in the public health response embarked upon during this polio event. The state and LGA team were committed and there was the timely arrival of training, logistics and social mobilisation funds. The national government and partner agencies adequately provided financial support and there was an excellent and efficient state cold chain system. Also, evening review meetings at state and LGAs helped in correcting gaps for the next day s work and there was intensive supervision by state team and partners during training and implementation. However, some gaps, including the non-release of counterpart funding by the state and LGA to aid logistics activities, late arrival of vaccines to the state, inadequate micro plans, poor team performance in the filing of the data tools and ineffective social mobilization, especially to schools and churches, were noted.

acute flaccid paralysis, oral polio vaccine, vaccine-derived polio virus

PMC9661556_01

Female

A 25-year-old recently married female presented to a tertiary care hospital in Anuradhapura, Sri Lanka, with a 3-week history of fever, malaise, cough, shortness of breath, and loss of appetite with mild hair loss for a few months. Her past medical history was unremarkable although one of her monozygotic triplet sisters had been diagnosed with SLE. On examination, she was febrile, and pale, with multiple lymphadenopathies involving the cervical, axillary, and inguinal groups along with facial puffiness and bilateral lower limb edema. Bi-basal fine end-inspiratory crepitation with hepatosplenomegaly was also noted. Investigations revealed a low hemoglobin level and thrombocytopenia, elevated erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and lactate dehydrogenase levels (LDH) (Table 1). Urine analysis showed proteinuria with red blood cell (RBC) casts. The 24-h urine protein quantification confirmed nephrotic range proteinuria and the urine protein:creatinine ratio (U:PCR) was 5.76 mg/dL. Bilateral pleural effusions and a left lower zone consolidation were noted in the chest x-ray. Ultrasound abdomen confirmed hepatosplenomegaly. Blood, urine, and sputum cultures were negative. She was started on intravenous co-amoxiclav and clarithromycin and two units of leukodepleted blood were transfused slowly. The initial ANA titer was negative. Conversely, the repeated test done 3 weeks later was found to be positive (titer:1:160), whereas simultaneous C3 (20 mg/dL) and C4 (10 mg/dL) complement levels were low (reference ranges: 50-120, 20-50 mg/dL, respectively). Anti-double-stranded DNA, virological studies for SARS-CoV-2, human immunodeficiency virus, Epstein-Barr virus (EBV), cytomegalovirus, hepatitis B and C were all found to be negative. Sputum, Mantoux, and polymerase chain reaction testing for tuberculosis yielded negative results. There was no echocardiographic evidence of infective endocarditis. Lymph node biopsy histology revealed reactive secondary follicles with hyalinization which were suggestive of CD. Bone marrow biopsy was negative for hematological malignancies or plasma cell disorders. Serum protein electrophoresis was negative for monoclonal gammopathy. The patient was referred to the consultant rheumatologist and was started on intravenous methylprednisolone pulse therapy (1 g per day for 3 days), oral steroid 45 mg per day, and hydroxychloroquine. She was taken over by the nephrology team for further management of renal complications of SLE. A dramatic improvement was noted clinically and biochemically with the normalization of inflammatory markers and platelet counts with the gradual but steady decline of proteinuria which has been normalized in 1-month review by the medical team (Graph 1(a) and (b)). Due to a satisfactory response to steroid therapy, renal biopsy was not opted for by the nephrology team at this point. Two months following her discharge, she was readmitted with pleurisy with pleural effusion suggestive of serositis. She was commenced on cyclophosphamide therapy as an adjunct by the pulmonologist.

castleman disease, systemic lupus erythematosus, antinuclear antibody, lymph node, lymphoid hyperplasia

PMC4836196_01

Male

We report a case of a 49 year old male, never smoker. He was homeless, born in Romania, and had been working as a smith. He had a clinical history of fatty liver disease (FLD) and renal lithiasis. He reported a history of wheezing since childhood, with non-productive cough, diagnosed at different stages as asthma. He had no family history of respiratory diseases, including tuberculosis (TB), or asthma and atopy. He was admitted to our Respiratory Unit with suspected pulmonary tuberculosis and with symptoms characterized by a low-grade fever with profuse sweating combined with productive cough of purulent sputum, dyspnea, wheezing, and chest pain. At diagnosis the patient showed a severe obstructive ventilatory deficit, not reversible after inhalation of short acting beta 2 agonists. A Chest X-Ray prescribed by his general practitioner showed diffuse interstitial thickening without parenchymal consolidation. He was treated with a broad-spectrum antibiotic but the symptoms persisted for a few weeks. Chest X-ray didn't show any parenchymal consolidation, whilst a High Resolution CT scan (HRCT) showed the presence of ground-glass opacity in the anterior segment of the right upper lobe, of suspected tubercular origin (Fig. 1). Physical examination of the chest was negative, with no superficial palpable lymphadenopathy. During hospitalization in our department of Respiratory Disease, an antibiotic therapy with ceftriaxone was established. Blood chemistry tests did not show any alteration of inflammatory indices. Sputum culture was negative for non specific flora, fungi and Mycobacterium tuberculosis. Serological tests were also negative for Mycoplasma pneumoniae, Chlamydiae, and Pneumotropic Viruses. No urinary antigen for Legionella or Pneumococcal infection was found. However, the patient tested positive at Quantiferon-TB and Tuberculin Skin Tests. A Fibrobronchoscopy finally revealed the presence of mucosal irregularities spread throughout the tracheobronchial system up to the segmental bronchi entrance, prevailing in the antero-lateral wall of the trachea and sparing the membranous pars, where a biopsy was performed (Figs. 2 and 3). The involvement of the segmental bronchi was also highlighted by HRCT (Fig. 4). Histological examination reported a mucosal tissue edged by a metaplastic epithelium, with underlying nodules of osseouscartilaginous nature, consistent with Tracheobronchopathia Osteochondroplastica (Fig. 5). Microbiological tests of Bronchoalveolar Lavage fluid were negative for Mycobacterium tuberculosis and also revealed an infection by Pseudomonas Aeruginosa, with bacterial load of one-million CFU / ml. Following an antibiogram, treatment with Amikacin was established, leading to a clinical and CT scan improvement.

rare diseases, respiratory sounds, tracheal disease, tracheobronchopathia osteochondroplastica

HRCT. Ground glass consolidation in anterior segment of right upper lobe.

PMC4836196_01

Male

We report a case of a 49 year old male, never smoker. He was homeless, born in Romania, and had been working as a smith. He had a clinical history of fatty liver disease (FLD) and renal lithiasis. He reported a history of wheezing since childhood, with non-productive cough, diagnosed at different stages as asthma. He had no family history of respiratory diseases, including tuberculosis (TB), or asthma and atopy. He was admitted to our Respiratory Unit with suspected pulmonary tuberculosis and with symptoms characterized by a low-grade fever with profuse sweating combined with productive cough of purulent sputum, dyspnea, wheezing, and chest pain. At diagnosis the patient showed a severe obstructive ventilatory deficit, not reversible after inhalation of short acting beta 2 agonists. A Chest X-Ray prescribed by his general practitioner showed diffuse interstitial thickening without parenchymal consolidation. He was treated with a broad-spectrum antibiotic but the symptoms persisted for a few weeks. Chest X-ray didn't show any parenchymal consolidation, whilst a High Resolution CT scan (HRCT) showed the presence of ground-glass opacity in the anterior segment of the right upper lobe, of suspected tubercular origin (Fig. 1). Physical examination of the chest was negative, with no superficial palpable lymphadenopathy. During hospitalization in our department of Respiratory Disease, an antibiotic therapy with ceftriaxone was established. Blood chemistry tests did not show any alteration of inflammatory indices. Sputum culture was negative for non specific flora, fungi and Mycobacterium tuberculosis. Serological tests were also negative for Mycoplasma pneumoniae, Chlamydiae, and Pneumotropic Viruses. No urinary antigen for Legionella or Pneumococcal infection was found. However, the patient tested positive at Quantiferon-TB and Tuberculin Skin Tests. A Fibrobronchoscopy finally revealed the presence of mucosal irregularities spread throughout the tracheobronchial system up to the segmental bronchi entrance, prevailing in the antero-lateral wall of the trachea and sparing the membranous pars, where a biopsy was performed (Figs. 2 and 3). The involvement of the segmental bronchi was also highlighted by HRCT (Fig. 4). Histological examination reported a mucosal tissue edged by a metaplastic epithelium, with underlying nodules of osseouscartilaginous nature, consistent with Tracheobronchopathia Osteochondroplastica (Fig. 5). Microbiological tests of Bronchoalveolar Lavage fluid were negative for Mycobacterium tuberculosis and also revealed an infection by Pseudomonas Aeruginosa, with bacterial load of one-million CFU / ml. Following an antibiogram, treatment with Amikacin was established, leading to a clinical and CT scan improvement.

rare diseases, respiratory sounds, tracheal disease, tracheobronchopathia osteochondroplastica

HRCT showed irregularity in main bronchi.

PMC5027129_01

Female

A 16-year-old girl first presented to the otolaryngology outpatient clinic at Bagcilar Training and Research Hospital, Istanbul, Turkey, with painless swelling of the neck. She also presented to the physical medicine and rehabilitation clinic with complaints of hip and low back pain that mimicked spondyloarthropathy. She had been treated with nonspecific antibiotics for cervical lymph nodes, but the size of the lymph nodes did not change with this treatment. She was followed for hip and low back pain by the physical medicine and rehabilitation clinic for a while, until she was finally referred to our outpatient pediatric clinic for evaluation of systemic disease. She denied cough, night sweats, or weight loss over the prior two months. She was admitted to the pediatric clinic on May 20, 2014. Her family history revealed that her father had been treated for tuberculosis ten years earlier. The patient did not have any underlying disease. She had a crowded family and their socioeconomic level was low. On physical examination, the patient was pale, with a temperature of 37.8 C, blood pressure of 120/80 mmHg, and a weight of 45 kg (3 - 10 percentile). Heart and lung auscultation were normal, and the patient had no hepatosplenomegaly. She had a 2 x 2 cm solid, painless lymph node in the right cervical region. Tenderness and limited range of motion were evident on hip joint examination, and a gait disorder was apparent. The laboratory findings were as follows: hemoglobin 10 g/dL; white blood cell count 5,800/mm3; platelets 704.000/mm3; C-reactive protein 104 mg/L; erythrocyte sedimentation rate (ESR) 74 mm/h; uric acid 5.2 mg/dL; and lactate dehydrogenase 192 U/L. Other laboratory data were normal. The Brucella agglutination test was negative and the peripheral smear revealed no pathology. Cervical ultrasonography showed hypoechoic lymphadenopathy. Hilar lymphadenopathy was seen on chest x-ray (Figure 1). We performed thoracic computed tomography (CT), which revealed a Ghon complex in the right lung and was suspicious for a Pott's abscess. Thoracic magnetic resonance imaging (MRI) confirmed a Pott's abscess involving the T8, T9, and T10 vertebrae (Figure 2), and pelvic MRI showed medullary trabecular edema in the right femoral head and neck combined with lobular cystic lesions in the peripheral muscle groups. With these MRI findings, we diagnosed the patient with tuberculous arthritis. Her purified protein derivative (PPD) skin test was 16 mm in diameter. The patient's features are summarized in Table 1. Sputum samples that received three consecutive days of staining for acid-fast bacilli were negative. The contact history and clinical and radiological findings aided in the diagnosis of bone and vertebral tuberculosis. A four-drug antituberculosis regimen was initiated (isoniazid, rifampin, pyrazinamide, and ethambutol). Our patient began to gain weight, and her pain lessened on the seventh day. On the fifteenth day, ESR was 33 mm/h and CRP was 2.3 mg/dL. The patient continued to be followed by the pediatric and orthopedic clinics, and she completed 12 months of tuberculosis treatment. There was no compression or neurologic deficits as complications of the spinal tuberculosis. The 10-month follow-up MRI of the hip showed decreased fluid in the joint space and regression of the abscess formation. At 12 months, her ESR was 2 mm/h and CRP was 0.48 mg/dL. The patient completely recovered after antituberculosis treatment.

child, osteoarticular tuberculosis, pott’s disease

PMC7457772_01

Male

A 78-year-old male presented with easy fatigue and awareness of heartbeat 2 weeks before admission. He reported multiple episodes of dizziness and weakness upon exertion. He did not report any history of bleeding from nose, mouth or stool. He did not complain of hematuria or reduced urine output. On examination, he had conjunctiva and palmar pallor with no palpable lymphadenopathy and no icterus. His chest and abdominal examination were relatively normal. He was initially found to have normocytic, normochromic anemia of 5.3g/dL and platelet count of 49x109/L. The peripheral blood smear did not show any evidence of abnormal morphology. A stool sample showed positive occult blood suspecting the patient to have an upper gastrointestinal (GI) bleeding. An esophagogastroduodenoscopy showed diffuse mucosal pallor with minimal inflammation only. An abdominal ultrasound was relatively normal. His control hemoglobin was 4.1g/dL after blood transfusion, suspecting ongoing bleeding. A colonoscopy showed clots under the superficial mucosa on different sites with superficial clots and fresh blood throughout the colon which could be explained by thrombocytopenia. Biopsy was not taken due to risk of bleeding. However, lesions in the caecum and terminal ileum could not be ruled out. At this point, he was suspected to have malignancy of the colon or inflammatory bowel disease. The carcinoembryonic antigen was 1.48ng/mL. Further workup showed him to have an INR of 1.3, repeat hemoglobin of 4.7g/dL and repeat platelets of 47x109/L. His general condition was not improving and had a poor performance status. A C-reactive protein showed 25,005ng/mL (normal 0-700ng/mL) and lactate dehydrogenase of 217.3U/L (normal 240.0-480.0U/L). Part of his liver workup showed serum albumin of 27.4g/L and a serum total protein of 99.7g/L. Following the elevated serum total protein levels, a serum creatinine and serum calcium were 485micromol/L and 3.91mmol/L, respectively. His skull X-ray showed multiple clear punched-out lesions in the skull bones (Figure 1). An abdominal computed tomography (CT) scan showed no obvious abdominal malignancy but detected osteolytic bone lesions on the thoracolumbar spine and pelvis (Figures 2, 3 and 4). All these lesions were present without reported bone pain. A serum protein electrophoresis showed M component 68g/L, kappa free light chain 16.0mg/L, lambda free light chain 974.0mg/L, kappa/lambda ratio of 0.016 and beta2-microglobulin 33.0mg/L. Given his poor performance status, he was initiated on cyclophosphamide 75% of the required dose and dexamethasone 20mg IV. Bortezomib was not given due to thrombocytopenia. Unfortunately, he was not fit to endure the next dose and passed away.

anemia, bleeding, gastrointestinal, multiple myeloma

PMC9395215_01

Female

A 45-year-old female patient, a city greening worker and was in good health before onset, was admitted to a local hospital in October 2017 due to cough and hemoptysis. At that time, she was diagnosed with pneumonia and bronchiectasis. She was given cephalosporin anti-infective therapy, but it did not work. Then, between January and March 2018, she visited other hospitals several times and was diagnosed with tuberculosis due to imaging findings (no Mycobacterium tuberculosis was found in sputum). Therefore, from April 2018 to April 2019, the patient received conventional (2HRZE/9HE) anti-TB therapy for about 1 year, but it was ineffective; cough and hemoptysis continued to occur repeatedly. Therefore, in November 2019, she came to our hospital for treatment. After admission, tuberculosis bacteria culture in sputum in November 2019 showed no M. tuberculosis complex group. Blood tests showed that the WBC was 5.42 x 109/L, the percentage of neutrophil was 0.77, the erythrocyte sedimentation rate was 58mm, PCT was 0.078ng/mL, and the C-reactive protein was 62mg/L; sputum smear was negative for acid-fast bacilli; and HIV antibodies were negative and antinuclear antibody was positive (1:1000). CTPA showed the following: Filling defect was observed in the main pulmonary artery, bronchial artery diameter was widened, and irregular patchy and nodular density was observed in both lungs (Figure 1A and B). Fiber-optic bronchoscopy was performed, which revealed a large amount of purulent secretions, bronchoalveolar lavage fluid (BALF) fungi (1-3)-beta-d glucan: 728.06, and GM test: 3.239. Pleomorphic fungi were observed by gram staining of BALF smear (Figure 2A and B). Acid-fast bacilli were not found in BALF smear and brush smear. Cryptococcus latex agglutination test was negative. No bacteria were cultured in BALF. No bacteria, fungi, viruses, parasites, M. tuberculosis, mycoplasma, chlamydia, or rickettsia were found by mNGS (BALF). CTPA and bronchial arterial angiography showed left bronchial artery-left pulmonary artery shunt (Figure 1A and B) and right bronchial artery-right pulmonary artery shunt. Fungal hyphae and spores were observed by gram staining of BALF smear. Two consecutive BALF fungal cultures grew A. mycotoxinivorans (Figure 2A and B), the identity of which was confirmed by internal-transcribed-spacer (ITS) sequencing. The phagocytosis of A. mycotoxinivorans by leukocytes was observed under the microscope (Figure 3). Intravenous amphotericin B liposome (30mg; 0 5mg/kg, QD) was given for 2 weeks, embolization was performed, and itraconazole (voriconazole allergy) was taken orally for 9 months after operation. Hemoptysis and pulmonary lesions gradually improved after treatment. Fiber-optic bronchoscopy was performed once again. Acid-fast bacilli were found on BALF smears two times, and Mycobacterium intracellulare was detected by mNGS. Oral rifabutin (0.3g qd), ethambutol (15-25mg/kg d), and clarithromycin (0.5, bid) were given for 6 months at the same time. The patient had clinical remission of pulmonary infection. After infection control, oral methylprednisolone (30mg qd) and hydroxychloroquine (0.2g bid Po) were given for 2 months for SLE. Re-examination of the lesion showed absorption, and no hemoptysis occurred in the patient after 6 months of follow-up.

apiotrichum mycotoxinivorans, bronchial artery–pulmonary artery shunt, hemoptysis, infection

PMC2782170_01

Female

A 17-yr-old female admitted with repeated periumbilical pain, nausea, vomiting and febrile sensation. Fourteen years ago, she was operated for intestinal tuberculosis. Physical examination revealed mild periumbilical tenderness without rebound tenderness. In laboratory data, white blood cell count was 12,800/microL and the other findings were normal. Simple abdominal radiography and abdominal computerized tomography revealed no abnormality except mild paralytic ileus. The following day a colonoscopy was performed, which revealed a polypoid lesion in the cecum (Fig. 1). An exploratory laparotomy was performed and it was seen dimple at cecum, the appendix invaginated into the cecum and an appendectomy was performed. However, we could not find any other pathologic lesions at the ileocecal region. The appendix was 2.5 cm in length, and it showed a chronic inflammation pathologically (Fig. 2).

PMC9829881_01

Female

A 9-year-old female of eastern Indian origin with no significant past medical history presented to the emergency room with abdominal pain, fever, nausea, and vomiting for 3 days. She had completed the 2-dose Pfizer-BioNTech COVID-19 immunization series 31 days before presentation to the emergency department. She had a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) polymerase chain reaction (PCR) test done for travel purposes 16 days prior to presentation which was positive. She was asymptomatic at the time of the test. A rapid antigen test was negative before leaving for travel. The patient traveled with her family to the US Virgin Islands for several days and was feeling well through her return. Parents did not notice any tick bites but did report multiple mosquito bites. A few days after returning to the United States, she developed persistent fever, emesis, nausea, and abdominal pain. Respiratory viral PCR panel (RVP) at the primary pediatrician's office was negative including for SARS-CoV-2. While waiting for the results of the RVP patient was given a dose of oseltamivir. She continued to have nausea, emesis, and decreased intake, as well as painful area at the tip of her tongue. Polymerase chain reaction tests remain the gold standard for COVID-19 testing. Home rapid antigen tests are intended to be used in serial testing. This patient had a positive PCR test and only one negative home rapid antigen test. Owing to persistent symptoms, she presented to the emergency department on her third day of illness. There, she was found to be persistently febrile, with maximum temperature of 40 C, heart rate between 124 and 133 beats per minute, respiratory rate between 20 and 30 breaths/min, with oxygen saturation 96% to 100%, and blood pressure 94 to 102/44 to 54 mm Hg. Her exam was unremarkable except for mild conjunctival injection and epigastric abdominal tenderness. Initial laboratory work-up was notable for mild hyponatremia, leukopenia, thrombocytopenia, lymphopenia, and elevated inflammatory markers (Table 1). Severe acute respiratory syndrome coronavirus 2 PCR was negative. Rapid streptococcal antigen test was negative. Urinalysis was notable for trace ketones, protein, small leukocyte esterase with white blood cell (WBC) 10 to 19, and few bacteria seen. On admission, the patient was started on 2 g/kg IVIG in addition to empiric ceftriaxone and doxycycline for possible bacterial infection. Antibiotics were discontinued after 72 hours once cultures were negative. Parasite and viral testing for diseases endemic to the United States Virgin Islands and northeastern United States were sent. This included Anaplasma, Babesia, dengue, Erlichia chaffeensis, Leptospira, tuberculosis, Parvovirus B19, Shigella species, enteroinvasive E. coli, Shiga-toxin producing genes, Campylobacter species (jejuni and coli), and Salmonella species. She developed a macular, nonpruritic, nonpetechial rash over the neck and hands with sparing of palm and soles approximately 5 hours after starting her IVIG treatment, and this did not abate until after IVIG was completed. She was also noted to have bilateral conjunctival injection without discharge on day 1 of admission which resolved by discharge. She was afebrile 24 hours after completion of IVIG treatment to the time of discharge. In addition to IVIG, the patient was started on 2 mg/kg/day prednisone due to continued symptoms. She also had intermittent episodes of confusion and agitation for the first few days of her admission, possibly related to the combination of systemic inflammation and/or known side effects of IVIG infusion and steroids. Owing to elevated d-dimer approximately 20x above normal at 10.87 ug/mL FEU, deep venous thrombosis (DVT) prophylaxis with low-molecular weight heparin was initiated. Anticoagulation was discontinued with decreasing d-dimer and worsening thrombocytopenia. Aspirin was discussed with cardiology but was not started while patient was thrombocytopenic, with an unremarkable echocardiogram. Her inflammatory markers trended downward after completion of IVIG; however, her pancytopenia persisted and reached a nadir of hemoglobin 9.7 g/dL, red blood cell count 3.61 M/uL, platelet count 30,000/uL, white blood cell count 2580 cells/uL, absolute lymphocyte count 240 (Figure 1). BNP increased to a peak of 4114 pg/mL on hospital day 3, and down trended to 429 pg/mL by day of discharge. Echocardiography remained normal at time of admission, after IVIG treatment, and after discharge. Because her hematologic abnormalities did not improve as expected with IVIG and steroid therapy, additional laboratory studies were obtained to exclude rheumatological conditions. Complement (C3 and C4) levels were normal; anti-nuclear antibody (ANA) was positive with titer 1:320; however, dsDNA and Smith antibodies were normal. Proinflammatory markers IL-6 and CXCL-9 were elevated at 284 pg/mL and 13 122 pg/mL, respectively. Hematologic workup included negative direct antibody test (DAT) which decreases the likelihood of autoimmune cytopenia. Her initial peripheral smear prior to the initiation of steroids was negative for blasts, and repeat smear while on steroids remained negative. A bone marrow aspiration to further evaluate the pancytopenia was considered but was not performed due to her parents' request. Thrombocytopenia began to improve on hospital day 7 and her platelet count was 104 000/uL at the time of discharge. The patient met criteria for MIS-C as defined by the American Academy of Pediatrics and Centers for Disease Control and Prevention: (1) she is under 21 years of age, with laboratory evidence of inflammation, requiring hospitalization, and had at least 2 systems involved; (2) other causes of her symptoms had been ruled out with extensive testing; and (3) she had a recent positive RT-PCR test for COVID-19.

covid-19, mis-c, inflammatory, pancytopenia, vaccination

PMC3563629_01

Female

We conducted a matched case-control study using a questionnaire that included exposures previously associated with STEC infections (e.g. ground beef), and exposures reported by >=50% of cases during hypothesis generation to identify exposures associated with infection in the 7 days before illness onset. Our analyses included 22 cases from Missouri that were identified as of November 2, 2011. Controls were individuals who did not have diarrhea in the month preceding the interview and were geographically matched to cases using a reverse telephone number directory of landline telephones. A list of 90-110 neighborhood control phone numbers was generated for each case, and we aimed to recruit three controls per case. Controls were proportionally recruited by age category to ensure similar distributions of cases and controls in the following age categories: <18 years old, 18-50 years old, >50 years old. Controls were interviewed about their exposures during the third week of October to match the exposure period of cases. All data were analyzed using SAS 9.3 (SAS Institute, Cary, NC) and exact conditional logistic regression models. Matched odds ratios (mOR) with exact 95% Wald confidence intervals are reported. The case-series study evaluated all cases, including those identified after the completion of the case-control study. Cases were interviewed by state and local health departments with a questionnaire that included exposures previously associated with STEC infections and exposures reported by >=50% of cases in the case-control study. Reported food exposures among cases were compared with the Foodborne Diseases Active Surveillance Network (FoodNet) Population Survey Atlas of Exposures, 2006-2007 to determine whether foods were eaten more frequently by cases compared to the FoodNet population. Ten state health departments comprised the 2006-2007 FoodNet sites which captures 15% of the United States population and assessed all food exposures in the seven days prior to interview of a randomly chosen subset of individuals who live in the FoodNet catchment area. We compared frequency of consumption of each food among patients in the case series to the FoodNet population using the binomial test. All data were analyzed using SAS 9.3 (SAS Institute, Cary, NC). Overall, 58 cases of STEC in 10 states matching the outbreak strain were identified: Arizona (1), Arkansas (2), Georgia (1), Illinois (9), Indiana (2), Kansas (2), Kentucky (1), Minnesota (2), Missouri (37), and Nebraska (1). Onset dates ranged from October 9 through November 7, 2011 (Figure 1). The median age of cases was 28 years (range 1-94 years); 61% were female. Among 50 cases with information available, 34 (68%) were hospitalized and three cases of 47 with information available (6.4%) developed hemolytic uremic syndrome (HUS). No deaths were reported. Figure 2a depicts the XbaI and BlnI pattern combinations associated with the outbreak investigation. Figure 2b depicts representative MLVA patterns associated with the outbreak investigation.

PMC7518491_01

Male

A 60-year-old South Indian male patient presented to the Head and Neck Surgical Oncology OPD with a chief complaint of swelling and pain inside the left ear of 3 months duration. Medical history revealed that the patient was hypertensive and diabetic with a history of angioplasty. Patient also recalled recurrent ear infection in the past. He is a chronic smoker (40 years), with a habit of tobacco chewing (for the past 1 year) and was taking alcohol in the past, which he quit around 12 years ago. Past family history revealed that patient's mother died of tongue SCC. On examination, a polypoidal growth was noticed involving the posterior and inferior walls almost filling the canal, with no clinically enlarged intra- or peri-parotid gland, pre/postauricular or neck nodes. He had already consulted a surgeon who had taken biopsy of the tumor located in the left EAC, for histopathological diagnosis. The hematoxylin and eosin slides and paraffin blocks of tissue were submitted for review at onco-pathology division of our institution. The slide was reviewed and reported as well-differentiated SCC. Radiological examination displayed an irregular enhancing lesion in the left EAC without bony invasion. There was no middle ear extension. The right EAC was normal [Figure 1]. Since the tumor was confined to left EAC without bony erosion or evidence of soft-tissue extension, the patient was categorized in Pittsburg stage I. After discussion in the multi-speciality board, lateral temporal bone resection (LTBR) with superficial parotidectomy, and selective neck dissection was done with preservation of facial nerve. Postauricular incision was placed extending anteriorly and approaching into the neck. Posterior-based flap was raised followed by cortical mastoidectomy. Antrum, facial nerve canal, and incus were identified. Using drill lateral temporal bone was delineated all around till ear ossicles, and the malleus and incus were removed. LTBR was completed using chisel and hammer. The facial flap was used to fill in the middle ear. Superficial parotidectomy was done with the preservation of branches of the facial nerve. Level II and III lymph nodes were dissected out, and the wound was primarily closed. Radical specimen received in our department constituted of left LTBR with left superficial parotidectomy and left level II to III cervical lymph nodes. The specimen was cut open, which revealed an ulceroproliferative growth of size 1.4 cm x 1.3 cm x 0.4 cm situated 1.1 cm from superior resected margin, 0.7 cm from posterior resected margin, 0.8 cm inferior resected margin, and 0.6 cm from the anterior margin. Sections from EAC lesion showed an invasive epithelial neoplasm composed of islands of tumor cells showing increased nucleo-cytoplasmic ratio, moderate nuclear pleomorphism, vesicular nuclei with prominent nucleoli, and abundant keratin pearl formation. Stroma showed dense inflammatory reaction [Figure 2a]. The temporal bone was free of tumor microscopically. All resected soft tissue, and bony margins and parotid gland were free of tumor. No perineural or lymphovascular invasion was seen. Two intraparotid lymph nodes were identified, larger node measured 9 mm. Smaller node showed reactive changes, while the larger node showed double-layered oncocytic epithelium arranged in complex papillary architecture and thin core composed of lymphoid tissue [Figure 2b-d]. Adjacent nodal tissue was unremarkable. Eight neck nodes showed reactive changes. A final diagnosis of pT1 N0 well-differentiated SCC of the left EAC (AJCC 8th edition) with incipient intraparotid lymphnodal WT was made. Figure 3a shows the gross specimen of LTBR specimen. The operated site healed uneventfully with no evidence of recurrence 1 year and 11 months after surgery [Figure 3b]. The patient is under close follow-up.

external auditory canal, stage i, warthin tumor, squamous cell carcinoma

PMC3096472_01

Male

We describe the case where a top MP athlete was supported by a program of acupoint stimulation over 7 years of his career. The program of acupoint stimulation was started when the 20-year-old athlete was nominated as a candidate for the national MP team. At that time the athlete reported that several factors limited his effective sports performance. These factors were severe epigastric pain and knee weakness during running, soreness in the wrist and fatigue of the dominant arm during fencing; general excitement and tremor of the dominant arm during the shooting contest; stiffness of the shoulder muscles during swimming. The program of acupuncture point stimulation was elaborated according to the symptoms, which have been associated with lower level of performance in each MP event. The decision for the choice of acupuncture points was strengthened by diagnostics, using distant computed scanning thermography. This diagnostic procedure was performed using the "Agema Thermovision 870" device with a measurement resolution of 0.13 C. The primary data, registered by scanning thermography were analyzed using the software, which correlated the localization of the skin areas, where the local temperature was changed, with the anatomical description of acupuncture points. Thermography of the athlete's body was performed at least three times daily after major competitions in which the athlete did not achieve the expected results, his performance being associated with the symptoms described above. arm fatigue during fencing:LI4, 10, 11; TH 5; stiffness of the shoulder muscles during swimming:LI4, 11, 14; TH5; GB21; general excitement and tremor of dominant arm during shooting:H7 and LI4. The acupuncture points, which had local temperature differences on the surface of the skin of the athlete identified by means of thermography, belonged to the stomach (ST36 and ST40), gall bladder (GB 31, 32, 34 and 40) and bladder (BL18 and 19) meridians. Based on these findings the acupuncture points ST36 and GB34 were recommended for stimulation before running (Figure 1(a)). Local acupuncture points were chosen to relieve (Figures 1(b) and 1(c)): In addition, before running and swimming, and during the fencing contest GV26 was stimulated, as the point for general tonification (Figure 1(d)). Acupuncture points were eventually stimulated by pressure and by electromagnetic millimeter waves. The time of stimulation ranged from 5 to 30 min, depending on the goal of treatment. After several applications by an experienced acupuncturist, the athlete himself and his coach were taught to perform the treatment. Immediately after the beginning of the acupuncture support program, the athlete improved his performance in 3000-m cross-country running from 10 minutes to <9 minutes and 25 seconds, because epigastric pain and knee weakness, which had been the major limiting factors during running were successfully relieved. Other symptoms (arm fatigue during fencing, stiffness of the shoulder muscles during swimming and general excitement and tremor of dominant arm during shooting) could be also successfully treated with the stimulation of acupuncture points. Figure 2 shows the increased ranking in international competitions (World Cup, World Championships, Olympic games) from the age of 20 years until the end of his sports career. During that time the athlete was among the best in the national MP team. The increased success of athlete's performance was attributed to the acupuncture program, although his coach reported a strong psychological effect of the treatment. Here we present a case report where the stimulation of acupuncture points in a talented young athlete was strongly associated with rapid significant improvement of his performance. This improvement remained stable under the program during his entire sports career. The choice of the acupuncture points for stimulation was directed to relieve the symptoms, which prevented him from achieving the desired results and was based on the experts' recommendations taken from a standard acupuncture textbook and enhanced by the diagnostics using distant computed scan thermography. We cannot rule out that the improvement of the overall performance described in this case report may have been due to the pure effect of training. However, the possible effects of acupuncture therapy deserve to be further explored, since several experienced athletes and coaches whom we contacted hesitate to explain the rapid and afterwards continuous improvement of his time in 3000 m cross-country running from 10 minutes to <9 minutes 25 seconds as being due to training effect alone. This improvement was achieved mainly due to complete relief from epigastric pain, which had been the main burden to the athlete during previous competitions. The relief other symptoms, which were considered to be the limiting factors (arm fatigue during fencing, stiffness of the shoulder muscles during swimming and general excitement and tremor of dominant arm during shooting) enabled the stable performance in these kinds of sports. It is known that a single stimulation of acupuncture points in trained athletes may substantially improve their results in light athletics, swimming and cycling. Kaada reported a mean improvement of 2.3 seconds in 800 m track racing (n = 5) and 4.3 seconds in 1000 m road racing (n = 9) after electric stimulation of LI4 acupuncture point compared to placebo stimulation in a crossover investigation in competitive track-and-field athletes. Regarding the fact that the site-specific acupuncture is effective only for a few conditions in clinical medicine it is plausible to explain the observed effects by non-specific physiological and psychological effects of acupuncture. Especially the placebo effect might play a great role, since placebo, in addition to physiological effects, may constitute 30-50% of the entire clinical effect of acupuncture. On the other hand, competitive athletes are extraordinary sensitive to placebo effects. Thus a survey among 48 top professional athletes showed that the majority of them (97%) believe that the placebo effect influences the success of sports performance. Seventy-three percent had experienced a placebo effect during their career and 10 athletes (33%) in the study offered explanations of the nature of the placebo effect. The expectancy-based placebo effect has been shown to produce the same performance improvement in trained athletes, as could be achieved using various pharmacological agents:caffeine and sodium bicarbonate in cyclists and anabolic steroids in weight lifting, thus even challenging the specific effect of these drugs. The enhanced motivation might be the other potential psychological mechanism, resembling the reward framework of placebo pre-conditioning and even acting through the dopaminergic system of basal ganglia, considered now as one of the main mechanisms of placebo. However, there are several reports on specific effects of transcutaneous electric acupuncture point stimulation (TEAS). In a series of experimental crossover investigations in competitive athletes, Kaada has shown that the runners (800 and 1000 m races) and swimmers (100, 200 and 400 m swimming) improved their personal results after TEAS in comparison with sham procedure where sub threshold electric stimuli were applied to acupuncture point LI4. The cause of the increased physical endurance in athletes in this investigation was suggested to be the result of reduced muscular tension, increased capacity of oxygen transport to the working muscles, increased capacity of the muscles to utilize oxygen and increased muscular microcirculation since the potential psychological factors (like placebo and motivation) were excluded by sufficient blinding of the study participants. The recent investigation of Lin et al. confirms the hypothesis of improved sports performance due to increased oxygen intake in competitive athletes. The authors found out that stimulation of auricular acupuncture points in male boxing athletes led to the enhanced recovery after exercise oxygen consumption using track treadmill in comparison with control condition. Another investigation, performed by So et al. in a crossover manner in healthy volunteers, demonstrated the site-specific effect of TEAS, where stimulation of specific acupuncture points of the calf enhanced the rate of muscle force recovery in comparison with stimulation of non-acupuncture sites. These investigations encouraged us to report the case of goal-directed acupuncture in the modern pentathlon, in order to propose to verify the suggested effects of acupuncture in appropriate randomized controlled trials. It is interesting, that sports physicians in China treat at least 70% of top athletes using traditional Chinese medicine including acupuncture, where both athletes and medical doctors believe in the energetic nature of acupuncture meridians. Regarding the increasing popularity of complementary and alternative medicine (CAM) among Western athletes:56% of athletes consume CAM in comparison with 36% of normal population, the question concerning the putative doping aspect of acupuncture and other CAM methods might be raised due to the existing criteria of doping definition. So far, acupuncture or other CAM methods are not on the list of substances and methods prohibited by World Anti-Doping Agency (WADA) at all times in and out of competition. According to existing WADA criteria, formally acupuncture has a potential to be included in this list. Indeed, according to the World Anti-Doping Code 2009, a substance or method shall be considered for inclusion on the prohibited list if WADA determines that the substance or method meets any two of the following three criteria: (i) medical or other scientific evidence, pharmacological effect or experience that the substance or method, alone or in combination with other substances or methods, has the potential to enhance or enhances sport performance; (ii) medical or other scientific evidence, pharmacological effect or experience that the use of the substance or method represents an actual or potential health risk to the athlete; (iii) WADA's determination that the use of the substance or method violates the spirit of sport described in the Introduction to the Code. We presume that criterion 2 would be irrelevant for acupuncture since rare serious complications, prospectively monitored in thousands of patients, were mainly due to needling procedure itself, which can be prevented using other non-invasive stimulation modalities. Nevertheless, according to existing WADA definition of doping, the combination of criteria 1 and 3 might be relevant for acupuncture and other CAM methods. However, if acupuncture has the potential to enhance or enhances sport performance (criterion 1 is fulfilled), we do not believe that the stimulation of acupuncture points violates the spirit of Olympic movement (criterion 2). Another target for doping suspect might be the potential analgesic mechanism of acupuncture, which is known to be associated with the activation of endogenous opioid system. Interestingly, placebo-induced analgesia is also mediated through the enhanced neurotransmission of endogenous opioids. Recently it was shown that placebo produces measurable opioid-mediated increase of physical performance. Benedetti et al. demonstrated that application of placebo injection on the day of competition induced an opioid-mediated increase of pain endurance and thus enhanced physical performance in healthy volunteers, who were conditioned with only two injections of morphine (one injection per week) before. This effect could be blocked by the administration of opioid-receptor antagonist naloxone. Alone these morphine-like effects of placebo raised the question whether the application of placebo is ethically acceptable in sports competitions, formally throwing the shadow of suspicion on all forms of mental training, psychological interventions and mind-body CAM techniques, which can enhance sport performance. However, we believe that precisely defined WADA criteria concerning CAM therapies, which can be used to enhance sports performance, will relieve these techniques from suspicion of doping potential in the future. Acupuncture and other CAM techniques, eventually used to enhance the sports performance, should be clearly distinguished from the methods with doping potential. For this purpose the existing WADA criteria concerning CAM methods should be clearly defined based on the experts opinion, involving clinicians, physiologists and specialists on ethics. Regarding this case report as the first step in the "ladder" of an evidence-based approach in clinical medicine, we suggested the idea of goal-directed stimulation of acupuncture points in athletes. As a logical next step the expected "performance-improving" effects of acupuncture and suggested specificity of acupuncture for this application should be verified using appropriate methodology of randomized controlled trials including the updated expert's guidelines on developing research of complex interventions.

PMC9610036_01

Female

A 70-year-old woman with atrial fibrillation, liver cirrhosis, Type 2 diabetes mellitus, hypertension, and venous thrombus treated with enoxaparin presented with a 5-day history of weakness in the left arm, numbness in the left fourth and fifth digits and medial palmar surface, and confusion. The patient also reported chronic vision loss in the right eye and denied headache or recent trauma. On initial examination, the patient was alert; oriented to person, place, and time; and disoriented to situation. Cranial nerve testing revealed reduced visual acuity in the right eye. Motor strength testing revealed 4/5 strength in the left triceps, left wrist flexors and extensors, and left finger flexors and 3/5 strength in the left finger extensors. Reflex testing revealed an absent left triceps reflex. Sensation testing revealed decreased sensation to pinprick and light touch in the fourth and fifth digits of the left hand. There was no dysmetria or dysdiadokokinesia. Head computed tomography (CT) without contrast demonstrated a 1 cm hyperdense round lesion in the suprasellar cistern [Figure 1]. The patient's limb weakness and numbness localized to either the C7/8 nerve roots or the middle and lower trunks of the brachial plexus. Our differential diagnosis included a lateralized mass in the extradural or intradural extramedullary spinal canal or idiopathic brachial neuritis. While the patient had several risk factors for embolic stroke, including atrial fibrillation and diabetes, the specific patterns of sensory loss in the left upper extremity and loss of the left triceps reflex were more suggestive of either nerve root or brachial plexus pathology. On hospital day 2, the patient developed a pupil-sparing right CN III palsy. The next day, the right pupil became dilated to 4 mm and nonreactive to light. The new cranial nerve palsy combined with the previously seen lesion on head CT without contrast broadened the differential diagnosis to include neoplastic, infectious, and inflammatory etiologies, especially those with a predilection for invading the subarachnoid space. Considerations included leptomeningeal disease from metastatic carcinoma or lymphoma as well as PCNSL due to the patient's age and multifocal nature of her symptoms, as well as tuberculosis, histoplasmosis, coccidioidomycosis, or cryptococcosis, and sarcoidosis. The patient then underwent gadolinium-enhanced brachial plexus, brain, and spine MRI in addition to lumbar punctures and several blood tests. The patient's Vitamin B12, Vitamin B6, folate, and lead levels were within normal limits. RPR was nonreactive and HIV-1 was negative. Hemoglobin A1c was mildly elevated to 6.7%. The ophthalmology service performed a slit-lamp examination, which showed only rare drusen. Gadolinium-enhanced brachial plexus and spine MRI were unrevealing. Gadolinium-enhanced brain MRI demonstrated enhancing lesions with heterogeneous signal intensity in the suprasellar, pineal, and right periatrial regions concerning for a lymphoproliferative, infectious, or inflammatory process and no evidence of ischemic stroke [Figure 2]. One week later, repeat gadolinium-enhanced brain MRI demonstrated an increase in the size of all enhancing lesions [Figure 3] in addition to focal right frontoparietal dural thickening. Chest/ abdomen/pelvis CT with contrast demonstrated multiple nodules in the thyroid concerning for metastases. CSF studies from two serial lumbar punctures, with respective volumes of 28 mL and 6.5 mL, demonstrated lymphocytic pleocytosis, elevated protein, and elevated IgG index but neither malignant cells nor other inflammatory and infectious markers. The neurosurgery service performed a stereotactic biopsy of the lesion in the right periatrial region, which established the diagnosis of diffuse large B-cell lymphoma. The patient was treated with whole-brain radiation (30 Gy in 10 fractions) rather than high-dose methotrexate due to the patient's decompensated liver cirrhosis. The patient had difficulty tolerating radiation due to severe, intractable nausea, and vomiting. Postradiation head CT without contrast demonstrated reduction in the size of the intracranial lesions [Figure 4]. Her mental status did not significantly improve, and the patient was ultimately discharged home with family and palliative care.

case report, multifocal, neurolymphomatosis, primary central nervous system lymphoma

PMC3123515_01

Male

A 69-year-old male with diabetes mellitus presented with epigastric pain and weight loss for 3 months. Examination revealed low grade fever and markedly raised jugular venous pressure. Chest radiograph demonstrated cardiomegaly and small bilateral pleural effusions. Transthoracic echocardiography demonstrated large pericardial effusion with cardiac tamponade. He underwent emergency pericardiocentesis and 1060 ml of hemorrhagic fluid was aspirated. Percutaneous pericardial biopsy was done to look for specific etiology. After pericardial biopsy, a 4-F pigtail catheter was left in the pericardial cavity for further aspiration. Exactly 5600 ml of hemorrhagic pericardial fluid was aspirated during the following 2 weeks. Pericardial fluid Gram stain and culture were negative for pyogenic or tuberculosis infection. Cytology did not reveal any malignant etiology. Repeat echocardiographic imaging revealed a large solid mass (7 x 10 x 8 cm) involving the right ventricular inflow, the body of the right ventricle and right ventricular outflow tract postero-medially. The mass appeared relatively fixed with possible myocardial infiltration [Figure 1a-c]. Cardiac catheterization and hemodynamic assessment showed biventricular heart failure. Right ventricular angiogram demonstrated a filling defect in the postero-inferior aspect of the right ventricle. Biopsy taken from that area using a bioptome revealed primary cardiac sarcoma of the malignant fibrous histiocytoma sub-group. He was offered tumor resection with chemotherapy but he did not accept. Initial computed tomography (CT) scan did not reveal any extracardiac tumor or metastasis. Echocardiographic evaluation at 6 and 8 months interval revealed enlarging tumor mass. The last echocardiogram demonstrated a huge right ventricular tumor measuring 20 x 10 cm, filling the entire right ventricular cavity and infiltrating through the right ventricular wall into the liver [Figure 2a and b]. He also had small pericardial effusion, bilateral pleural effusions, ascites as well as hepatic and splenic metastasis. He continued to refuse any treatment and expired at home 16.5 months after the initial presentation.

echocardiography, metastasis, pericardial effusion, primary cardiac sarcoma, right ventricular mass

PMC9731151_01

Male

An 83-year-old male presented with uncontrolled hyperglycemia and abdominal pain for a week. On the abdomen CT scan, a 3.5 x 2.5 cm sized pancreas body mass invading the common hepatic artery was noticed with intrahepatic, common bile duct dilatation, and small peritoneal nodules. Endoscopic ultrasound-guided fine needle aspiration for pancreatic body mass was conducted, and cytologic diagnosis showed a few clusters of atypical cells, resulting in the diagnosis of adenocarcinoma. Peritoneal carcinomatosis was found in the PET CT. After an overall examination, he was diagnosed with PDAC, cT4N1M1, stage IV. The patient received two cycles of cytotoxic chemotherapy: gemcitabine and albumin-bound paclitaxel. His disease continued to progress, as evidenced by the increasing size of the pancreatic body mass (3.6 x 3.0 cm) and the increased amount of ascites, thereby being determined as a progressive disease according to RECIST 1.1 criteria. Although mFOLFIRINOX could have been used as second-line palliative chemotherapy in the country, the patient's condition would have been intolerable considering his performance status. Tumor molecular profiling using next-generation sequencing (FoundationOne Liquid CDx) was performed through liquid biopsy with a blood sample from the patient. The patient exhibited microsatellite stability, and the blood tumor mutational burden was 0 Muts/Mb. The genomic findings revealed the mutations of BRAF NVTAP deletion ( Figure 1 ), PTEN G127R, CDKN2A/B p16INK4a V25fs*12, MUTYH splice site 892-2A>G, and TP53 R248Q. Table 1 summarizes the tier according to ESCAT and VAF each genomic alteration. As mentioned above, BRAF NVTAP deletion is reported as an oncogenic mutation in PDAC. There was a single previous case where dabrafenib was used to target BRAF NVTAP deletion, and the clinical effectiveness of dabrafenib was demonstrated in this mutant (20). We requested and obtained dabrafenib/trametinib from Novartis with the Managed Access Program. After receiving dabrafenib 150 mg twice a day and trametinib 2 mg once a day for 8 weeks, a radiologic evaluation showed a marked decrease in primary pancreas body mass (50 mm to 36 mm) with improved ascites ( Figure 2 ). Findings were rated as a partial response according to RECIST 1.1 criteria, and it was maintained for 6 months with continued treatment. The toxicities of drugs such as pyrexia, headache, diarrhea, and rash were not noticed. However, unfortunately, the patient died of an outbreak of SARS-CoV-2 infection during treatment.

braf mutation, braf short in-frame deletion, ngs, dabrafenib/trametinib, pancreatic ductal adenocarcinoma

PMC9703999_01

Male

A 31-year-old man, with a family history of pulmonary tuberculosis, smoker 15 pack-years, presented to our consultation of pneumology with right latero-thoracic pain for three weeks associated with productive cough, night sweats and weightloss. Findings of physical examination were unremarkable. Electrocardiogram was normal. The hematology laboratory tests were also without abnormalities. The liver and renal functions were normal. The chest-X-Ray was also normal. Chest computed tomography (CT) revealed multiple bilateral excavated nodules with associated alveolar involvement made of ground glass nodules and parenchymal condensation of the right lower lobe. Bone window showed costal involvement of the middle arch of the 3rd left side with heterogeneous osteolytic lesion with invasion of the soft parts (Figure 1, Figure 2 ). The initial clinical presentation was in favor of pulmonary tuberculosis or pulmonary metastasis associated with bone metastasis. Pulmonary tuberculosis was suspected but overturned after the sputum mear results for Koch's bacillus was negative. Bronchial fibroscopy was refused by the patient. For anatomopathological confirmation, we accessed to the bone lesion since it is more accessible to biopsy. Needle biopsy of the rib lesion showed an abundant cellular infiltrate. This infiltrate contains sheets of oval mononuclear cells characterized by unique reniform or cleaved nuclei with pale cytoplasm and many eosinophils, plasma cells and lymphocytes are present with positive and diffuse staining with Cd1a (Figure 3 ). Diagnosis of Langerhans cell histiocytosis (LCH) was retained.As part of the disease assessment, we completed by radiological explorations. MRI of brain and pituitary gland was normal. Bone scintigraphy showed a focus of hyper fixation in the sternum, the rest of the skeleton was of normal fixation.A level 2 analgesic has been prescribed .At 3, 6 and 12 months of follow-up, there was an improvement of pain with spontaneous resolution of the other symptoms.

PMC4338053_01

Female

A 48 year-old woman was admitted to our hospital with a history of non-radiating pain in the right upper quadrant and epigastrium associated with nausea and bloating (dyspepsia) for the past 20 days. There was no previous history of TB or contact with any TB patient. At the time of admission, on physical examination, except tenderness in the right upper quadrant, no other physical finding was detected. Lab tests: hemoglobin 11g/dl; white blood cells 10000/mm3 (78% neutrophils); platelet count 270,000/mm3; erythrocyte sedimentation rate: 35/mm at the end of the first hour; blood urea 25mg/dl; creatinine level 0.9mg/dl; total bilirubin of 1mg/dl with direct component of 0.4; AST 24U/L; ALT 32U/L (normal range for AST is 17-59U/L and for ALT is 21-72U/L). Routine and microscopic examinations of stool revealed no cyst or ova; blood for amoebic serology was negative. HIV test was negative. Chest x-ray (CXR) was normal. Ultrasonography (US) of the abdomen revealed a hypoechoic lesion measuring 43*35mm in the anterior and sub capsular right lobe of the liver suggestive of an abscess. All other abdominal viscera appeared normal with no free fluid. A computerized tomographic (CT) scan of the abdomen showed sub capsular, well-defined cystic lesions in the right liver lobe (Figure 1). Then, 20 cc of pus was aspirated under US guidance and sent for microbiological investigations. Routine bacteriological cultures of the aspiration fluid were negative for bacterial infection and fungus. The patient was started on parenteral metronidazole 750 mg/tds and ciprofloxacin 400 mg/bid for 14 days with provisional diagnosis of amoebic or pyogenic liver abscess. Due to poor response to initial treatment, US was repeated and showed persistence of the liver abscess in the anterior and sub capsular right lobe. Repeated aspiration under CT guidance was performed and 10 ml of the cloudy cream-colored pus was sent for Ziehl-Neelsen staining, acid fast bacilli [AFB] culture, polymerase chain reaction (PCR) for TB and other routine microbiological investigations and cytology; which were all negative but the sample was positive on PCR for Mycobacterium tuberculosis and diagnosis of TLA was made. Then, laparoscopy was performed and peritoneal biopsy showed granulomatous peritonitis with caseating necrosis most compatible with TB. The four first line systemic anti TB drugs (isoniazid 300mg/ po, rifampin 600mg/ po, pyrazinamide 1500mg/ po, ethambutol 1000mg/ po) were started. The patient is currently receiving anti TB medications and is asymptomatic. The repeat US of the liver revealed regression of the abscess.

hepatic tuberculosis, immunocompetent, tubercular liver abscess

PMC6538955_01

Male

A 20-year-old male, born in Ecuador, without any antecedents of significance, presented with 3 months of non-productive cough. By history there was also unquantified weight loss, asthenia, intermittent fever and night sweats. Two weeks before admission he had exacerbation of fever, lower limb weakness, severe headache, inability to walk, and urinary incontinence. Vital signs revealed a 39 C fever. General physical examination showed poor general condition, and presence of crackles in both lungs. Neurological examination showed neck stiffness, positive Brudzinski and Kernig's signs, arreflectic lower limbs, paraparesis in both lower limbs (strength 0/5 according to the Medical Research Council grade), and a positive Babinski sign. Routine blood tests were normal. HIV and VDRL serologies were negative. Chest X-ray showed evidence of diffuse interstitial micronodular pattern compatible with military TB, while the CT scan showed the similar pattern plus a 18 mm cavitary lesion on in the left upper lung. Brain CT scan showed no pathological findings. Cerebrospinal fluid (CSF) analysis revealed glucose 5.4 mg/dL, proteins 131.4 mg/dL, white cells 87 mm3 (polymorphonuclear 60%, mononuclear 40%) red cells 280 mm3, and negative India ink staining. Considering the possibility of TB meningitis, the patient was empirically treated for TB initially with isoniazid 300 mg, rifampicin 600 mg, pyrazinamide 1100 mg, and ethambutol 1600 mg daily. Due to the presence of paraparesis, there was a suspicion of transverse myelitis, so dexamethasone 8 mg was administered IV every 8 h. Ceftriaxone 2 g twice a day for 7 days was added to cover other possible bacterial meningitis. Subsequently sputum AFB smear result was positive and cerebral magnetic resonance imaging (MRI) showed a right cerebellar nodule, compatible with tuberculoma (Fig. 1). Spinal cord MRI (done after treatment initiation) revealed intramedullary T1, T2 and STIR hyper intense signals extending from T7 to T9 segments; confirming the suspicion of transversal myelitis (Fig. 2). At 30 days after the spinal tap, the result of CSF culture was positive for Mycobacterium tuberculosis. At 19 days after treatment initiation, the patient fully recovered lower limbs sensitivity and motor capacity. Soon afterwards, the patient was discharged and continued TB treatment as an outpatient for one year, including oral corticosteroids during 2 months, without any adverse effects of pulsed corticosteroid therapy. One month after discharge, the patient was able to walk alone. Two months after treatment initiation, the patient was completely recovered without any residual neurological deficit.

neurological tuberculosis, transverse myelitis, tuberculosis

PMC5903156_01

Female

A 61-year-old woman with NVG was referred to our department with left ocular pain and blurred vision for a duration of 5 days. She had been treated for diabetes mellitus 4 years ago with hypoglycemic agents and for asthma 10 years ago with bronchodilators. At the first visit, the best-corrected visual acuity and IOP were 20/40 and 13 mm Hg in the right eye and 20/60 and 37 mm Hg in the left eye, respectively. The right eye showed no inflammation in the anterior segment and posterior segment. The left eye showed ciliary hyperemia, infiltrating cells, hyphemia, rubeosis iridis, and cataract in the anterior segment (Fig. 1a, b); however, vitreous opacity or retinal vasculitis was not observed in the posterior segment (Fig. 1c). Gonioscopy examination detected nodules and rubeosis on the trabecular meshwork in the left eye. Fluorescence angiography did not detect any retinal vasculitis or retinal ischemia caused by diabetes mellitus (Fig. 1d). Serum examination detected slight increases in blood glucose (201 mg/dL), HbA1c (6.8%), and erythrocyte sedimentation rate (17 mm/h). C-reactive protein, angiotensin-converting enzyme, and interleukin-2 receptor were within normal ranges. Bilateral hilar-mediastinal lymphadenopathy was not detected on chest X-ray. Serum herpes simplex virus (HSV) IgM, HSV IgG, cytomegalovirus (CMV) IgM, CMV IgG, and CMV antigen were negative, and a multiple broad-range polymerase chain reaction (PCR) test using anterior humor did not detect human herpes virus (HHV) 1-8, 16S rRNA, 28S rRNA, tuberculosis, or toxoplasmosis. We diagnosed the left eye as NVG caused by unknown anterior granulomatous uveitis, and topical corticosteroid (0.1% betamethasone 6 times/day) and anti-glaucoma agents (0.005% latanoprost 1 time/day, 0.1% brimonidine 2 times/day, 0.4% ripasudil hydrate 2 times/day, and 0.5% dorzolamide 3 times/day) were initiated. beta stimulant was not used because of asthma. On the next day, IOP was still high (28 mm Hg), and additional oral acetazolamide 500 mg/day was initiated. After 1 week of treatment, inflammation and rubeosis iridis had diminished (Fig. 1e), and IOP had decreased to 20 mm Hg. After 1 month, inflammation and rubeosis iridis had completely resolved, and IOP had decreased to 13 mm Hg (Fig. 1f). Gonioscopy also detected the regression of hyphema and rubeosis. Treatments were then tapered, and there was no recurrence for 1 year.

inflammation, neovascular glaucoma, rubeosis, topical corticosteroid, uveitis

PMC7580750_01

Female

A 12-year-old girl was referred to the dental department for the assessment of a long-standing nonhealing ulcer on the labial mucosa of the lower lip. The lesion was first observed by the patient 2 years ago; however, the lesion was brought to the notice of the parents 6 months back which prompted them to seek the treatment. The patient had no symptoms otherwise. The size of the ulcer has remained constant over the past 2 years. There was no history of cough, fever, hemoptysis, and weight loss. She did not have any systemic condition, had no history of allergy, and was not on any medications. She had consulted two dental practitioners in her village and was treated conservatively with the help of topical medications over the past 6 months. The older prescriptions revealed the use of mucopain gel (benzocaine 1.P. 20%), zytee gel (benzalkonium chloride 0.02%, choline salicylate 9%), and candid mouth paint (clotrimazole 1%). However, there was no change (increase or decrease in the size of the ulcer) or improvement in her clinical condition for the past 6 months. General physical examination revealed that she weighed 33 kg and was 150 cm tall. The calculated body mass index of 14.7 kg/m2 indicated that she was underweight. Vital signs (heart rate - 82 beats/min, respiratory rate - 16 breaths/min, blood pressure - 120/80 mmHg, body temperature - 98.6 F) were within the normal range. Submandibular and submental groups of lymph nodes were examined and they were nonpalpable and nontender. Oral examination revealed a round nonhealing ulcer on the labial mucosa of the lower lip on the left side measuring 4 cm x 4 cm. The ulcer was grayish-white in color with irregular borders. The edges were thin and undermined with slight induration at the base [Figure 1]. There was no tenderness on palpation. An incisional biopsy was performed under local anesthesia. The microscopy section from the lower lip showed the hyperplastic squamous epithelium, multiple granulomas composed of epithelioid cells and Langhan's giant cells, surrounded by lymphocytes and plasma cells [Figure 2]. No caseous necrosis was seen in the biopsy sample obtained. A preliminary diagnosis of TB/sarcoidosis was made. Blood tests revealed a normal erythrocyte sedimentation rate (18 mm in the 1st h). The serum angiotensin-converting enzyme level was 58.2 U/L. Interferon-gamma release assay (IGRA) (Quantiferon-TB [QFT]) was positive (3.43 IU/mL). Results of Mantoux test interpreted 48 h after tuberculin injection (10 T.U) revealed erythema of 16 mm and induration of 18 mm. The chest radiograph revealed the absence of foci of infection indicating no pulmonary involvement. Thus, the diagnosis of primary TB was confirmed. Treatment with anti-tubercular drugs was initiated. The patient was prescribed isoniazid 150 mg, rifampin 300 mg, pyrazinamide 750 mg, and ethambutol 400 mg daily for 2 months. The second phase of the treatment consisted of isoniazid 150 mg and rifampin 300 mg daily for 4 months. Lesion almost resolved within 3 weeks of initiation of the treatment [Figure 3].

children, oral ulcer, primary, tuberculosis

PMC3881079_01

Female

We report on a 58-year-old Caucasian woman that was hospitalized owing to a monstrous ovarian tumor on the right side with a three-month history of sudden abdominal growth and subsequent dyspnea. Sonography and CT scan rendered an additional myomatous uterus with requirement of a bilateral hysterosalpingectomy. The last consultation with a gynecologist had been about eight years prior. The complete staging was without evidence of further neoplasms and the patient was otherwise healthy. The patient had eight deliveries and one abortion. She finally was referred to a dermatologist because of multiple agminated dense erythematous nodules restricted to the skin of the left shank and the right flank with a few aberrant lesions at the dorsal trunk only (Figure 1). The patient reported occasionally associated painful sensations but did not request further treatment. The nodules obviously had rapidly appeared in the context of alvine tuberculosis at the age of 13. However, a relapse of the previous mycobacteriosis was excluded upon punctuation of the ovarian tumor. Histopathologically, there was evidence of a severe fibroleiomyomatosis of the uterus with an associated dexter ovarian cystadenoma (diameter 25 cm) (Figure 2). A biopsy of the cutaneous lesions on the right flank revealed pilar leiomyomas consisting of a plaque-like confluent fascicular spindle cell proliferation obviously originating in the muscles of hair erection. Nuclei were cigar-shaped and in part exhibited vesicular pseudoinclusions. There was no mitotic activity. However, some plump cells were seen and interpreted as a clue to ancient changes (Figure 3). Smooth muscular differentiation was confirmed immunohistochemically by coexpression of actin, desmin and smooth muscle actin. The proliferation index as detected by nuclear Ki67 expression was less than 1%. Blood samples with addition of EDTA were analyzed molecularpathologically and a complete deletion of the fumarate hydratase gene was detected.

fumerate hydratase, ovarian cystadenoma, uterine leiomyomatosis

PMC8236769_01

Female

The 79-year-old, nonsmoking, Asian female presented to our hospital with a persisting cough and signs of aspiration pneumonia that lasted more than 1 year. The patient had a history of pulmonary tuberculosis about 50 years ago. Chest computed tomography showed a fibrotic change in the right lower lobe basal segment and suspicious finding of the nearby esophageal diverticulum. Water-soluble contrast esophagography showed a BEF at right side wall of mid to lower esophagus (Figure 2A). Esophagogastroduodenoscopy confirmed BEF in the esophageal diverticulum at 30 cm from the incisors (Figure 1). The patient underwent uniportal VATS under general anesthesia with one-lung ventilation. An incision was made in the sixth intercostal space of the mid axillary line. The soft tissue and intercostal muscles were retracted with an X-small wound retractor (Alexis; Applied Medical) to secure the intercostal space. A 5-mm, 30 video thoracoscope and endoscope instrument were used. Dissection of the diverticulum and the fistulous tract was done with Ligasure (Valleylab, Covidien), and fistulectomy and diverticulectomy was done with endoscopic linear staplers. The muscular layer of esophagus was approximated with interrupted sutures. There was no bronchial and esophageal defect. The parietal pleural flap was interposed between bronchial and esophageal ends of the divided fistula. At the end of the surgical procedure, a chest tube (24 Fr) was inserted through a single incision (Figure 3). The postoperative course was uneventful. On postoperative day 5, esophagography was performed to detect any esophageal leakage. There was no evidence of contrast leakage (Figure 2B). The patient resumed diet and discharged on postoperative day 6. No recurrence has been observed during 3 months follow-up in the outpatient clinic to date.

vats, bronchoesophageal fistula, esophageal diverticulum, uniportal video-assisted thoracoscopic surgery

PMC8355976_01

Female

The patient was a 9-year-old girl with a family history of AI. At the time of the visit, the patient was in a stage of mixed dentition but all the primary teeth had been extracted by her primary dental care provider due to multiple secondary decays. The permanent first molars and the upper central incisors were less severely involved and successfully restored with direct composite. The patient was referred for treatment of the lower incisors very sensitive upon thermal stress and unsightly due to abnormal shape, size, and color. The appearance of the lower incisors made the girl uncomfortable with her smile, and she reported bullying at school because of her teeth. Intraoral clinical examination of the lower incisors revealed missing enamel in the incisal half and reduced enamel thickness in the cervical half of the teeth (Figure 1). Radiographic examination showed normal enamel radiopacity and normal contrast with the underlying dentin (Figure 2). Based on the clinical and radiological examinations, a diagnosis was made of AI type I according to the Witkop classification. Type l is the most common form of AI caused by a mutation in the enamelin gene ENAM 4q215 transmitted by autosomal dominant inheritance. This mutation introduces a disruption in the presecretory and secretory stages of amelogenesis resulting in a layer of hypoplastic enamel with normal mineralization but reduced thickness. The treatment options for restoration of the lower incisors were discussed with the patient and her parents, and a final decision was made to restore the teeth with prefabricated composite veneers. Once the treatment plan with prefabricated composite veneers was approved, the clinical procedure started with veneer size selection. The prefabricated composite veneers for the patient in this report (Edelweiss Veneers, Edelweiss Dentistry, Wolfurt, Austria) (Figure 3) are available in four sizes (XS, S, M, and L) based on average tooth dimensions in the human population. A custom sizing guide is included in the system to select the veneer that best fits the patient (Figure 4). If none of the available sizes fits the patient's teeth, the width and length of Edelweiss Veneers can be altered to accommodate specific dimensional requirements. For the patient in this report, Edelweiss Veneer size M was selected, and no width or length alteration was required. However, the thickness of the veneer was reduced with a football shape diamond bur (8379, Komet USA, Rock Hill, SC, USA) to allow a more conservative tooth preparation (Figures 5 and 6). Using the same football shape diamond bur, the cervical margin of the veneer was finished to a knife-edge configuration for maximum tissue preservation in the gingival area where the enamel layer is thinner. Thanks to the combination of minimal thickness of the composite laminate and knife-edged configuration of the cervical margin, no tooth preparation was required and the thin hypoplastic enamel layer of the AI patient was fully preserved. After veneer size selection, the next step was choosing the shade of the luting composite (Figure 7). Luting composite color selection is a critical step for successful restoration with Edelweiss Veneer because the laminate is fabricated with a colorless enamel shade, and the final color of the veneer is determined by the color of the luting composite. The Edelweiss Veneer System includes a high-viscosity nanohybrid composite for cementation available in several dentin and enamel shades (Edelweiss NH, Edelweiss Dentistry, Wolfurt, Austria). For the patient in this report, Edelweiss NH shade A2 was selected with the addition of an opalescent flowable composite in the incisal area (Effect Blue, Edelweiss Dentistry, Wolfurt, Austria) to increase incisal translucency and highlight the halo effect. After size and shade selection, the intaglio of the veneer was conditioned with a proprietary resin primer (Veneer Bond, Edelweiss Dentistry, Wolfurt; Austria) applied with a microbrush and light cured 20 seconds according to the manufacturer recommendations (Figure 8). No acid-etching, no sandblasting, and no silane application are required inside Edelweiss Veneer. However, the manufacturer recommends internal conditioning with Veneer Bond to promote chemical adhesion and to increase bond strength between the highly inorganic laminate and the luting composite. After Veneer Bond application, the veneers were ready for delivery and the working field was isolated with a rubber dam and a 212 Hu-Friedy clamp and the first lower incisor was etched with 37% H3PO4 (Gel Etchant, KerrHawe, Bioggio, Switzerland). Etching gel application started from enamel and after 15 seconds moved to dentin for another 15 seconds for 30 s (Figure 9) followed by water rinsing for 30 s and application of a single-step adhesive according to the manufacturer instructions (Scotchbond Universal, 3 M ESPE, Seefeld, Germany) (Figure 10). Then, the veneer was loaded with the selected composite shade (Figure 11) and seated on the deserving tooth (Figure 12). After gently pressing the veneer in position, the extra composite was removed with a thin spatula (CompoSculp DD 9/10, Hu-Friedy, Chicago, Ill, USA) and carefully sculpted to achieve optimal adaptation between the veneer and the tooth. Then, the veneer was light cured 20 seconds from the lingual and 20 seconds from the buccal using a high-power (1.330 mW/cm2) curing light (Demi Plus, Kerr Corporation, Brea, CA USA) (Figure 13). Finally, the margins of the veneer were finished with composite finishing discs (Sof-Lex XT, 3M ESPE, Seefeld, Germany) (Figure 14) and interproximal finishing strips (Sof-Lex, 3M ESPE, Seefeld, Germany) (Figure 15) followed by a diamond-impregnated silicone cup (Dia step 2, Ravelli, Milano, Italy) at 7500-10,000 rpm under water to produce the final luster. Once the same step by step clinical procedure was completed for all the four veneers, the patient was dismissed and rescheduled for postoperative evaluation after two weeks. At the recall appointment functional evaluation (absence of fractures, marginal adaptation), biological evaluation (soft tissue response, postoperative sensitivity), and esthetic evaluation (gloss, color matching) were completed and resulted fully satisfactory (Figure 16). Radiological examination showed successful integration of the restorations (Figure 17). The patient was happy with the esthetic outcome and reported that hypersensitivity disappeared after placing the veneer. A second recall appointment was scheduled 6 months after delivering the veneers. At the new follow-up visit, the veneers resulted fully functional with no marginal discoloration and no alteration of the original superficial luster (Figure 18). The veneers showed good soft tissue response, and the patient's oral hygiene was significantly improved as reported by the RDH who has been following the patient since the initial phase of the treatment. AI patients often experience difficulty in maintaining good oral hygiene on account of the increased tooth sensitivity that makes tooth brushing uncomfortable and the rough tooth surface that facilitates plaque accumulation. Also the impaired smile appearance with abnormal tooth shape, size, and color contributes to poor oral hygiene motivation. Previous research demonstrates that a strong correlation exists between attractive smile appearance and positive oral health behaviors, and a secondary benefit of the esthetic restoration of the young AI patient presented in this report was the positive impact on the patient's strive to maintain optimal oral health.

PMC4731740_01

Female

A 4-year-old girl presented with a history of multiple episodes of seizures since the last one and half years. The seizures were varying in semiology:initially multifocal with secondary generalization and later tonic seizures with frequency gradually increasing from once every 6 months to once every 2 weeks. There was no fever, vomiting or headache. On examination, she had papilloedema and brisk deep tendon reflexes. Weight was 13 kg (<15th centile) and blood pressure 110/70. Other systems were normal. There was no focal neurological deficit. On investigation, haemogram, chest X-ray was normal. Computed tomography (CT) scan brain showed evidence of a large conglomerate ring enhancing focal lesion in the parafalcine frontal cortices mainly on the left side with extensive white matter hypodensity in both frontal lobes (Fig. 1). Small tuberculomas were also seen in the left occipital lobe and left lateral inferior cerebellum, tegmentum of pons and right temporal lobe. Magnetic resonance imaging (MRI) brain showed a 5.7 x 3.9 x 4.8 cm-sized heterogeneously hyperintense peripherally enhancing conglomerate lesion involving the left frontal parafalcine region crossing onto the midline and right parafalcine frontal lobe, extending into the genu of the corpus callosum and showing patchy restricted diffusion. The lesion showed extensive perilesional vasogenic oedema (Fig. 2) with multiple ring and disc enhancing lesions seen in the bilateral cerebral and cerebellar parenchyma and in the right hemipons. Magnetic resonance spectroscopy revealed lactate double peak and diffuse reduction in all the metabolite peaks suggestive of tuberculoma. The Mantoux test was negative. Patient was started on i.v. dexamethasone, which was given for 5 days, and subsequently lumbar puncture was done. Cerebrospinal fluid (CSF) examination was normal. CSF Gene Xpert revealed no Mycobacterium tuberculosis complex, and TB MGIT was negative for Acid Fast Bacilli. Antitubercular treatment (ATT) with isoniazid (10 mg/kg/day), rifampicin (10 mg/kg/day), ethambutol (20 mg/kg/day) and pyrazinamide (35 mg/kg/day) along with oral prednisolone at 2 mg/kg/day was started on Day 5 of hospitalization. The child improved, seizures stopped and the papilloedema gradually disappeared. A neurosurgical opinion for biopsy of lesion was taken, but in view of classical MRI findings, it was deferred. Follow-up MRI brain after 8 months of treatment showed a mild reduction in the size of the lesion to 4 x 4 x 2.3 cm with mild perilesional vasogenic oedema. The ring enhancing lesions in the bilateral cerebral hemispheres were still present. However, the cerebellar and pontine lesions had disappeared (Fig. 3). Child is on regular follow-up.

PMC6901822_01

Male

A 25-year-old male was diagnosed with AML-M2 1 year ago, according to the French-American-British classification. Bone marrow (BM) morphology revealed 62.2% blasts, and peripheral blood (PB) was manually sorted by 39% blasts. The morphology examination exhibited megakaryocyte dysplasia, erythrophagocytosis, vacuolation in both cytoplasm and nucleus in leukemia cells in BM (Figures 1A-D). Immunophenotyping by flow cytometry (FCM) analysis revealed positive results for CD34, CD38, HLA-DR, CD13, CD33, CD15, CD64, CD11b, CD56, CD117, CD123, MPO, and CyCD3 in BM. His karyotype showed 46, XX, t(4;8) (q28;q24.1,t(16;21) (p11.2;q22) /46, XY (Figure 1E). The FUS-ERG fusion gene was positive at 21.96% quantitatively in BM. He received induction chemotherapy DA (daunorubicin, cytarabine) and reinduction MA (mitoxantrone, cytarabine) and achieved CR. Then, he received two cycles of chemotherapy MA and IDA (idarubicin, cytarabine) and achieved minimal residual disease (MRD) negative by FCM. He received a human leukocyte antigen (HLA)-matched unrelated donor allo-HSCT after cyclophosphamide and total body irradiation (TBI) as preconditioning followed by Cyclosporine A (CsA), mycophenolate mofetil (MMF), basiliximab and short-term Methotrexate (MTX) for prophylaxis of graft-vs-host disease (GVHD). He achieved MRD-negative CR 1 month after HSCT but relapsed 2 months later. Then, he successively received DCAG (decitabine, cytarabine, aclacinomycin, G-CSF), DMA (decitabine, mitoxantrone, Ara-c), and CLAG (cladribine, Ara-c, G-CSF) combined with donor lymphocyte infusion (DLI) and achieved transient CR with MRD positive. He developed an anal fissure and perianal abscess, and the infection was controlled by anti-infective therapy. He subsequently relapsed 1 month later with central nervous system leukemia (CNSL) and was administered four cycles of Ara-c, MTX, and DXM by intrathecal injection and CLAG + DLI. CNSL was controlled, but the disease progressed (Figure 2A). The patient received reduced-intensity conditioning (RIC) regimen of TVFB (therarubicin 60 mg on d1 and 40 mg on d2-3; teniposide 200 mg on d1 and 150 mg on d3 and d5; fludarabine 50 mg on d1-5; and busulfan 3 mg/kg on d6-8) and CART123 1 day after preconditioning. The total infused CART123 was 1.1 x 108 cells, and 9 x 107 cells (CAR+ 80.2%) were CAR+ cells (1 x 106/kg). This second-generation CAR consisted of anti-CD123 single chain fragment variable (scFv), CD8a hinge region, CD8 transmembrane domain, 41BB costimulatory domain, and CD3zeta cytoplasmic region. Truncated human Epidermal Growth Factor Receptor (EGFR) polypeptide (tEGFR) was integrated with CAR gene through a P2A peptide (Figure 3A). The viability was 89.0%, and the CD4+/CD8+ ratio was 1.81. Of the infused cells, 98.2% were CD3+ cells principally composed of the CD8+ subset (30.2%) and CD4+ subset (54.7%), and 8.43% and 90% of CAR+ cells were characterized with the central memory phenotype (CD45RO+/CD62L+) and effect memory phenotype (CD45RO+/CD62L-), respectively (Figure 3B). Both the stem cells and the CAR T cells were from his father, who exhibited a 5/10 HLA loci matching and ABO incompatibility with the patient. Subsequently, 4 days after CART123 infusion, anti-thymocyte globulin (ATG; 2.5 mg/kg/d 3d) was administrated for prophylaxis GVHD. However, during the second infusion of ATG, the patient developed tachypnea, tachycardia, and persistent hypoxemia. Given these serious side effects, the third-day infusion of ATG was canceled. Instead, the prophylactic regimen is adjusted to basiliximab (20 mg/d; days 0, 4, and 8), CsA, MTX (0.33g d1 0.02g d3, 6), mycophenolate mofetil (MMF; 1.8g 1/day 1.5g 1/night), and ATG (2.5 mg/kg/d 2d). Granulocyte colony-stimulating factor-mobilized peripheral blood stem cells (G-PBSC) was infused (mononuclear cells 11.77 x 108/Kg, CD34+ 4.8 x 106/Kg, CD3+ 4.1 x 108/Kg) 6 days after CART123 infusion. Considering the potential hematopoietic toxicity of CART123, the second infusion of PBMC will be performed to promote implantation if the hematopoietic system remains unrecovered within about 14 days (Figure 2C). The blasts in BM decreased from 40.8 to 10.3% by FCM 6 days after CART123 infusion and decreased from 38 to 8% by morphology 14 days after CART123 infusion. On day 18, the second donor engraftment achieved 97.7% in BM. Although G-CSF was administrated to promote implantation from day 6, the hematopoietic system remains unrecovered until day 16. Thus, cyclophosphamide (4150mg) was administered as conditioning regimen and G-PBSC was infused again on day 18 and day 19 (mononuclear cells 14.28 x 108/Kg, CD34+ 4.74 x 106/Kg, CD3+ 4.44 x 108/Kg). On day 32, blasts in BM were 0.5, 0.05, 0.042, and 0.02% by morphology, FCM, Wilms tumor-1 (WT1) and FUS-ERG detection, respectively. Compared to the first allo-HSCT, the second allo-HSCT was conducted in non-remission status using a RIC regimen, indicating the anti-leukemic activity of CART123. The patient achieved myeloid implantation on day 42 but was not weaned from platelet (PLT) and red blood cell (RBC) transfusion (Figures 2A,B). The proportion of T lymphocytes (CD3+, CD4+, and CD8+) in PBMC was significantly increased after CART123 infusion. Then, T cells were sharply reduced after the administration of medications, such as methylprednisolone, ATG, and basiliximab (Figure 3C). Direct evidence of CART123 amplification was detected by qPCR (Figure 3D). The patient developed a fever (>39 C), hypotension (92/58 mmHg) and pneumonia within 24 h after infusion, and these effects were evaluated as grade 3 CRS. He was immediately administered tocilizumab, a pressor agent and empirical anti-infective therapy. Assessment of cytokines in serum revealed an increasing trend for IL-6 and IFN-gamma, and the effects in IL-6 was most obvious. Four days later, dyspnea, progressive pneumonia, and fever persisted (up to 41 C), and these features were evaluated as grade 4 CRS. The changing trend of C-reactive protein (CRP), lactate dehydrogenase (LDH), and body temperature was consistent with the level of cytokines and the clinical symptoms of the patient. Considering that tocilizumab on days -5 (240 mg) and -3 (400 mg) was invalid, methylprednisolone was administered from days -2 to 8 (day 4-7: 2 mg/kg for the first dose, 1 mg/kg q12h; d8-10: 2 mg/kg q12h) and the dose was gradually decreased. CRS was rapidly controlled after the infusion of methylprednisolone and ATG, with the decline of CRP, LDH, body temperature, and IFN-gamma (Figures 4A-C). The patient has an anal fissure before transplantation, and then it progressed to anal fistula with perianal infection after transplantation. However, the perianal infection caused repeated sepsis and pneumonia. Intermittent fevers occurred and were accompanied by sharp elevations in CRP and LDH after allo-HSCT. Repeated anti-infective, symptomatic and supportive treatment was administered to the patient and exhibited effective results. On day 28, he developed disseminated intravascular coagulation (DIC) due to infection and was controlled by the symptomatic treatment (Figure 4C). On day 32, after CRi was achieved, he soon developed fever, vomit, stomachache, and severe diarrhea. Total bilirubin (TBiL) progressively increased, mainly direct bilirubin (DBiL). He was diagnosed with aGVHD and administered by CsA, glucocorticoids (GC), MMF, basiliximab, tacrolimus, and maraviroc were successively for the treatment of aGVHD. On day 48, a total number of 7 x 107 umbilical cord blood mesenchymal stem cells (UCB-MSC) were administered for the treatment of aGVHD. Finally, he was diagnosed with grade IV aGVHD involving liver and gut. In the final stage, creatinine increased progressively, reflecting the deterioration of renal function. Unfortunately, the patient died of aGVHD, severe pneumonia, intestinal obstruction, and multiple organ failure on day 56 (Figure 4D).

cd123, fus-erg, acute myeloid leukemia, allogeneic hematopoietic stem cell transplantation, chimeric antigen receptor, cytokine release syndrome, graft-vs-host disease

PMC5156792_01

Male

A 75-year-old man was hospitalized for mental confusion, muscular weakness, and severe hypokalaemia (2.5 mEq/L). The patient's medical history included hypertension and benign prostatic hyperplasia; he took ramipril 5 mg and dutasteride 0.5 mg daily. Few months before he had felt an increasing asthenia, he noted weight gain and the worsening of hypertension control and he experienced some episodes of low urinary tract infections. The laboratory tests evidenced the onset of diabetes (fasting glycaemia 160 mg/dL and HBA1C 50 mmol/L); prostate-specific antigen (PSA) was normal (2.39 mug/L). His wife reported that lastly he was physically exhausted and mentally confused. At physical examination the patient was 165 cm in height and he weighed 70 kgs (BMI 25.7); he showed slight round face and thin arms and legs; his arterial pressure was 160/105 mmHg. Digital evaluation revealed that the prostate was enlarged and firm in consistency. Laboratory tests (Table 1) confirmed severe hypokalaemia (2.3 mmol/L) and documented high levels of midnight salivary cortisol (50.6 mug/L), elevated levels of plasma ACTH (155.4 ng/L), and plasma cortisol (398 mug/L). The overnight 8 mg dexamethasone suppression test did not properly suppress plasma cortisol (198 mug/L); high levels of plasma chromogranin A and calcitonin (272 ng/L) were also documented; PSA was confirmed to be normal (1.7 mug/L) (Table 1). Magnetic Resonance Imaging (RMI) of the pituitary gland was normal; no nodules were found by thyroid ultrasonography. Total body computed tomography (TBCT) (Figures 1(a)-1(b)) revealed a voluminous prostate gland (maximum diameter of 10 cm) heterogeneously enhancing the contrast medium. The tumour of the prostate had invaded the bladder; the rectum and multiple pathological retroperitoneal lymph nodes as well as bilateral enlarged adrenal glands were evident. A subsequent 68 Gallium DOTATATE PET/CT found a high uptake of the whole prostate (SUV max 12.7) and of the adjacent lymph nodes, confirming the presence of a neuroendocrine tumour in that site and excluding other distant metastases (Figure 2). The patient underwent a transurethral prostate biopsy that showed a small cell prostate cancer focally positive for ACTH and calcitonin and negative for chromogranin A and PSA at immunocytochemistry (Figures 3(a) and 3(b)). Continuous intravenous potassium infusion, potassium sparing drugs (Aldactone), and antihypertensive drugs were administered to the patient. Ketoconazole was also administered with an uptitrating dose of 400 mg/twice daily for 5 weeks and because of the poor control of cortisol secretion, octreotide 0.1 mg every 8 hours subcutaneously was added for further 13 days. Despite a reduction of plasma cortisol (195 mcg/L) after 6 weeks of treatment, no significant clinical benefit was achieved; in fact the patient continued rapidly to worsen becoming more asthenic and confused since he developed a glucocorticoid induced psychosis. The surgeon urologist excluded prostate resection and bilateral surrenectomy because they were considered too dangerous for the patient. The patient started a cycle of chemotherapy with epirubicin and carboplatin, but few weeks after the first cycle, febrile neutropenia, sepsis, and intestinal perforation occurred and the patient died.

PMC5835238_01

Female

A 16-year-old female teenager reported that she began to present with edema of her right leg at the age of three at which time she sought treatment; however, the cause of the swelling was not diagnosed. At ten years of age, she also observed that her left leg was swollen, and at the age of 13, a lymphoscintigraphy was performed which detected lymphedema of all four limbs, arms, and legs. At 16 years of age, after erysipelas, the edema of the lower limbs worsened and clinically identifiable lymphedema of the right arm was observed, especially the hands, so she sought the Clinica Godoy for treatment. A volumetric evaluation was performed of all four limbs, and an intensive 8-hour treatment program was proposed. The adolescent was submitted to manual (Godoy & Godoy technique) and mechanical lymphatic therapy (RA Godoy) of the lower limbs, cervical lymphatic therapy (cervical stimulation), and the continuous use of a grosgrain stocking. A reduction in the size of all four limbs was observed at the end of the 5-day treatment program without using any therapies specifically to treat the arms (Table 1). Maintenance of the results also used the grosgrain stocking and mechanical lymphatic therapy (RA Godoy) of the legs at the patient's home. In the maintenance phase, the patient was advised about the need of skin care. Moreover, she performed myolymphokinetic exercises of both the legs and arms, prioritizing activities that require little effort and did not involve impact or repetitive movements that could aggravate the edema. The patient was asked to return for monitoring by the care team every three months; however, she did not return. Only after four years, she returned to the service to treat an outbreak of erysipelas of the legs and the accompanying worsening of the lower limb lymphedema. At this time, she did not present with edema of the arms (Table 2). Thus, the initial intensive treatment for leg lymphedema was sufficient to treat the arm lymphedema. This case report was approved by the Research Ethics Committee of FAMERP (# CAAE: 27810214.6.0000.5415).

PMC6588154_01

Male

A 25-year-old man had a fall during a football match where his right leg was trapped under his body. He had pain over the ankle and especially proximally in the leg. Inspection revealed a prominent fibular head (Fig. 1). Stability testing of the right knee showed no instability and the peroneal nerve was intact. X-rays (of both legs/knees) showed an anterolateral dislocation in the proximal tibiofibular joint (Fig. 2). The dislocation was treated with closed reduction under spinal anesthesia. The joint was then stable when tested. He avoided weight bearing for 2 weeks. At 6 months follow-up, the patient played football at the same level as before the injury.

dislocation, proximal fibula, tibiofibular joint

PMC3707272_01

Female

A 42-year-old female presented to Surgical OPD of our hospital, with history of lump in the upper inner quadrant of her right breast, for which lumpectomy was done outside and sent for histopathological examination, one month back, histopathology report was given as Invasive ductal carcinoma. There was no history of any nipple retraction and discharge, no significant past history of tuberculosis, and so forth. The patient was afebrile with no abnormality detected on general physical examination. Local examination of the right breast showed a linear scar mark, medial to the nipple. The breast was tender to touch while no mass lesion was felt. Left breast was unremarkable with no axillary lymphadenopathy. In view of the histopathology report, right-sided modified radical mastectomy (MRM) was performed at our hospital and excised specimen was sent for histopathological examination. Right MRM specimen measuring 17 x 16.5 x 3 cm and weighing 500 gms was grossed. Overlying skin showed a scar mark. Serial cut section revealed a cavity (postlumpectomy); however, no any residual tumor could be appreciated on gross examination, representative bits were processed, and H&E stained tissue sections were obtained. Outside slide and blocks reported as invasive ductal carcinoma were also reviewed. On light microscopy, outside slides (from lump) showed a tumor composed of large cells arranged in tubules, glandular pattern, and sheets, having abundant eosinophilic granular cytoplasm with distinct cell margins, large round nuclei with vesicular chromatin pattern, and occasional prominent nucleoli. Tumor cells showed PAS positivity with diastase resistance. Bloom Richardson score was 2 + 2 + 1 = 5 (Grade I). Also noted was marked adenosis with apocrine metaplasia in the adjacent breast tissue (Figures 1 and 2). Sections from MRM specimen revealed minimal residual tumor with surrounding breast tissue showing marked adenosis with apocrine metaplasia. Also noted was foreign body giant-cell reaction in the overlying skin:consistent with prior history of surgery (lumpectomy). Final diagnosis was given as invasive apocrine carcinoma, right breast, with minimal residual tumor in MRM specimen. All lymph nodes, surgical margins, skin, nipple, and areola were free from tumor. Immunohistochemistry was done which showed estrogen and progesterone receptor negative, androgen receptor positive (ER-/PR-/AR+).

PMC9444644_01

Female

ILS, a 44-year-old female homemaker complained of sudden fullness in the left ear a year before, followed by daily serosanguineous to purulent otorrhea, with progressive hearing loss and tinnitus. She denied prior otorrhea, vertigo, or contact with tuberculosis. She had received prior treatment with amoxicillin/clavulanate, ciprofloxacin, and topical gentamicin/betamethasone. The patient had SLE, controlled with prednisone 10 mg/day. She had no cervical lymphadenopathy and the oral cavity, pharynx, and rhinoscopy were normal, with normal VII function bilaterally. The right otoscopy was normal; the left otoscopy disclosed whitish mucous secretion at the bottom of the ear canal. Laboratory tests were normal. Computed tomography (CT) showed pneumatized mastoids, with the left appearing opaque without erosions. Audiometry showed ipsilateral moderate mixed hearing loss. Chronic suppurative otitis media (CSOM) was suspected. A tympanomastoidectomy was performed, which disclosed friable whitish tissue in the mastoid and middle ear without cholesteatoma, anvil erosion, or misidentified stirrup. A mastoid debridement was performed, followed by specimen collection and fascia graft. Ossiculoplasty was left for a subsequent procedure. The patient evdeveloped tinnitus, progressive wound dehiscence, otorrhea, and afacial paresis that recovered in three weeks. She was started on azathioprine and prednisone 40 mg. Two months later, the mastoid was fully exposed (Fig. 1), and tuberculosis was suspected. The material collected during surgery was insufficient to establish the diagnosis. She had a non-reactive PPD and normal chest X-ray. A biopsy performed through the dehiscent incision showed extensive granulomatous reaction with, giant multinucleated epithelioid cells with focal necrotic areas. Fungus and AFB culture results were negative. Considering these data, the physicians decided to establish an early antituberculosis regimen: rifampicin, isoniazid, pyrazinamide, and ethambutol for two months, followed by isoniazid and rifampicin for seven months. Improvement in healing was observed after 30 days (Fig. 1). After three months, the incision was closed. One year later, she remained with tinnitus, discrete otorrhea, and tympanic perforation. Audiometry showed no responses at 6 and 8 kHz, with preservation of thresholds at the other frequencies.

PMC6199967_01

Female

A previously healthy 44-year-old woman presented with intermittent episodes of bilateral upper limb numbness over 8 months with worsening symptoms associated with bilateral hand clumsiness and unsteady gait in the past month. She denied having any sphincter dysfunction. Her neurological function status was Nurick grade III. Cervical MRI scan was prescribed for detecting possible pathological conditions. The patient's general physical examination was unremarkable. The pathologic findings on neurological examination were as follows: spastic quadriparesis that was most prominent on the left side, hypoesthesia mainly between C5 and T1, exaggerated deep tendon reflexes on the left side limbs, and a positive Babinski's sign in the left foot. There was reduced vibration and position sense in the left toe and ankle. Rectal tone and sensation were both normal. The patient also exhibited Romberg's sign and spastic-ataxic type gait disturbances. T2-weighted MRI examination of her cervical spine revealed a hyperintense C2-C5 intramedullary lesion with spinal cord expansion and edema extending rostrally into the medulla and caudally to the thoracic spinal cord (Figure 1). There was no contrast enhancement. We therefore decided to perform microsurgical tumor resection with the aid of a unique imaging protocol that allowed application of high-field ioMRI in combination with neurophysiological monitoring of somatosensory and motor-evoked potentials (MEPs). For the ioMRI T2WI-detected hyperintensity zone, the area was first explored under microscopic guidance. Following tumor confirmation, the resection was performed under stringent control of MEP neuromonitoring. The design prevented us from mistaking operation-induced hyperintensities as tumor masses. Our approach, with enhanced safety measures for patient protection, augmented surgical completeness of IMSCT resection in a multiple operating room (OR) setting that did not have a designated ioMRI operation suite. At Bahcesehir University, Goztepe Medical Park Hospital, any of the six operating rooms in our surgical theater is designed to have access to the ioMRI (MRW450) system between surgical procedures or stages (Figure 2). Implementation of this novel concept permits that each OR can be assigned for its routine operations with prephased access to ioMRI assistance. Furthermore, the use of MR compatible headrest-head coil unit (General Electric Healthcare, Chi-cago, IL, USA) allows the patient to be imaged directly at planned procedure time point. The surgical tables (Maquet GmbH, Rastatt, Germany) used in our OR are adapted to be interchangeable with an MRI compatible transfer table that enables transient transportation of patient to MRI gantry under general anesthesia. In the present case, the patient was positioned and fixed in prone position for posterior midline approach to the cervical intramedullary region. The thorax and pelvis of the patient were supported by silicon pads. At time of transfer, the operative field was covered with a new drape, coverings beyond the operative field were removed, and the patient was transferred through the connection door to the ioMRI system. Then, the MRI head coil was mounted on the headrest. After ioMRI scanning, the patient was brought back to the operating table, with a new drape being placed on the operative site followed by a general redraping. Images were processed and displayed immediately after acquisition in the monitoring room (Figure 3). Each step was controlled manually, and the members of the surgical team (ie, the primary surgeon and assistant surgeon, anesthesiologist, and radiologist) supervised the transfer to ensure patient safety. The primary neurosurgeon and radiologist interpreted the ioMRI results before refinement microsurgery was performed to ensure a complete removal of the neoplastic mass (Figure 3; Supplementary video). The surgically removed tumoral tissue was preserved in The Bahcesehir University Tissue Bank (BUTB). BUTB maintains a tissue database with links to our general clinicopathological data storage. The tissue sample was snap-frozen in liquid nitrogen immediately after surgical removal and subsequently transferred from the OR to the tissue bank's liquid nitrogen bank for long-term storage and future analytical studies.

decompression, glioma, intraoperative imaging, residual tumor, spinal cord, spine

PMC7289762_01

Female

A 44-year-old woman, lifelong resident of the northern suburbs of NYC, with a past medical history of polycystic ovarian syndrome was referred to our institution after a 9mm right lower lobe (RLL) pulmonary nodule (PN) was detected incidentally on computed tomography (CT) of the abdomen performed for nephrolithiasis. Review of systems was negative for constitutional and respiratory symptoms. She was a never-smoker and denied relevant occupational exposures. Vital signs, physical examination, and routine laboratory evaluation were unremarkable. Testing for the human immunodeficiency virus (HIV) and an interferon-gamma release assay for Mycobacterium tuberculosis (IGRA-MTB) were both negative. Chest CT performed five months after the abdominal study revealed an increase in size of the solid RLL PN to 11mm (Fig. 1) along with mediastinal and right hilar lymph nodes all measuring less than 1cm in short axis. Neither the PN nor the intrathoracic lymph nodes demonstrated avidity for 18fluorodeoxyglucose (18FDG) on 18FDG-positron emission tomography (18FDG-PET). Cytology from endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) of the right hilar lymph node revealed a mixed cellular population consisting of lymphocytes and neutrophils against a background of extensive necrosis. No organisms were seen on lymph node cytology; bronchoscopic cultures returned negative for bacterial, mycobacterial, and fungal organisms. With the leading pre-operative diagnosis of neoplasia, the patient underwent wedge resection of the PN via video-assisted thoracoscopic surgery. Tissue examination revealed necrotizing granulomatous inflammation associated with small yeast-like forms exhibiting narrow-based budding, morphologically consistent with H. capsulatum (Fig. 2). Fungal cultures of the resection specimen yielded no growth. Antibodies against H. capsulatum and Coccidioides were not detected in the serum by either complement fixation or immunodiffusion. She was prescribed a six-week course of oral itraconazole. Upon further questioning, she reported having vacationed in Puerto Rico, an endemic region for histoplasmosis, within a year of her diagnosis. On that trip, she engaged in cave exploration.

blastomycosis, coccidioidomycosis, endemic mycoses, histoplasmosis, new york state

Axial image from a CT scan of the chest set to lung window showing a solid 11mm nodule in the right lower lobe behind the diaphragm.

PMC7289762_02

Female

A 36-year-old woman residing in the northern suburbs of NYC was referred for outpatient pulmonary evaluation of a lung nodule. Her past medical history was significant for locally advanced endocervical adenocarcinoma, which had been managed with abdominal hysterectomy and bilateral salpingo-oophorectomy one year earlier. No adjuvant therapy was administered. Preoperatively, 18FDG-PET/CT revealed a 1.2cm hypermetabolic RLL PN with a maximal standardized uptake ratio (SUVmax) of 2.3 (Fig. 3A). Transthoracic needle biopsy of this lesion was performed and showed poorly defined granulomatous inflammation with negative stains for microorganisms. Tissue cultures were not obtained. On repeat 18FDG-PET/CT one year after the initial study, the PN was not appreciably changed in size but now had a cavitary appearance with an increase in SUVmax to 5.18 (Fig. 3B). At the time of her visit to the pulmonary clinic, she denied constitutional and respiratory symptoms. She was a never-smoker and had no relevant occupational exposures. Since arriving to suburban NYC from Ecuador three years prior to the visit, she had not traveled. Her vital signs, physical examination, and routine laboratory evaluation were unremarkable. HIV testing was negative, and antibodies against H. capsulatum were not detected. IGRA-MTB was positive, but serial sputum collection for acid fast bacillus smear and culture was negative. She then underwent bronchoscopy with bronchoalveolar lavage (BAL). No microorganisms were seen on cytological and potassium hydroxide (KOH) preparations of the fluid. Eventually, however, BAL fungal culture yielded growth identified as Coccidioides spp. Since she remained asymptomatic, clinical observation was chosen over antifungal therapy. On further questioning, the patient revealed that she had migrated to the United States from Ecuador through northern Mexico, entering into Texas and from there ultimately reaching New York by air. Both northern Mexico and Texas are locations in which Coccidioides spp are endemic.

blastomycosis, coccidioidomycosis, endemic mycoses, histoplasmosis, new york state

A, Axial image from the CT portion of a18FDG-PET/CT study set to lung window showing a spherical, solid 1.2cm subpleural nodule in the right lower lobe. The nodule's maximal standardized uptake value on the PET portion (not shown) was 2.33.