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PMC4293552_01

Male

A 51-year-old male was admitted to our hospital for incomplete extension and tingling sensations in his left fourth and fifth fingers for 2 months.He was a left handed-carpenter with no prior history of illness and had experienced no fever, night sweats, or weight loss. His Eastern Cooperative Oncology Group performance state score was 0. Physical examination revealed that the fourth finger of his left hand was bent towards the palm and his left fourth and fifth fingers could not be fully extended. A subcutaneous mass on the left palm along the fifth finger without erythema or tenderness was noted. Nerve conduction velocity of the left median and ulnar nerves, and electromyogram of the left upper extremity, were normal. Ultrasonography revealed a 29 x 10 mm hypoechoic mass at the tendon sheath of the left fourth and fifth flexor digitorum profundus (FDP) (Fig. 1A-C). Tenosynovectomy of the left fifth finger was planned under the preoperative diagnosis of Dupuytren's contracture. Upon surgery, inflammatory hypertrophied tenosynovial tissue enveloping the flexor tendon sheaths of the third to fifth fingers, and necrotized lumbrical muscle of the third to fifth fingers were observed (Fig. 1D). As infective tenosynovitis was suspected, tenosynovectomy of the third to fifth FDP tendon and excision of necrotized lumbrical muscle of the respective fingers were performed. Bacterial and tuberculosis cultures were negative. Histopathologic examination showed diffuse infiltrative atypical cells with geographic necrosis (Fig. 2A and 2B). Immunohistochemical staining for CD20 was negative (Fig. 2C), and CD56, CD3, and Epstein-Barr virus encoded RNA were positive (Fig. 2D-F), confirming the diagnosis of ENKL. A positron emission tomography-computed tomography scan showed increased fluorodeoxyglucose uptake at the left fourth and fifth fingers, and left axillary lymph node. Lactate dehydrogenase was increased up to 280 IU/L. Polymerase chain reaction for Epstein-Barr virus was negative. During the staging workup the patient's left palm began to swell and he developed fever. The fever was thought to be B symptom-related because it occurred almost a month after surgery and did not appear to be infection related. The Ann Arbor stage was IIBE, the international prognostic index (IPI) score was 1, and the Korean Prognostic Index (KPI) was 3. The patient was treated with three cycles of SMILE chemotherapy followed by autologous HSCT. The subject remained disease-free at the 2-year follow-up. Natural killer/T-cell lymphomas usually occur in middle-aged patients. They present as localized disease in about two thirds of patients; however, there is a high frequency of B symptoms despite apparently limited disease and rare bone marrow involvement. Our patient was middle-aged and had B symptoms, despite localized disease without bone marrow involvement. The prognosis for ENKL is poor, even though more than half of ENKL patients have IPI scores of less than 2. Because IPI is not efficient at discriminating between low- and low-intermediate risk groups, a new prognostic model, KPI, was proposed. Our patient was allocated to group 4 based on the KPI model, indicating poor expected survival. There is no established treatment protocol for extranasal ENKL, and outcomes remain poor when it is treated with cyclophosphamide, doxorubicin, vincristine, prednisolone (CHOP), radiotherapy, or a combination of the two. A recent retrospective study by Jo et al. reported that SMILE was relatively effective as a first-line therapy for extranasal ENKL, and Kwong et al. showed that extranasal ENKL patients treated with SMILE had good response rates. Autologous HSCT has also been shown to confer a survival benefit in patients who attained complete response on post-remission consolidation therapy, especially those patients with a high KPI score at diagnosis. Thus, our patient was treated with SMILE followed by autologous HSCT, and has remained disease-free for 2 years. In conclusion, this is the first case report of extranasal ENKL of the tenosynovium of the hand. It was successfully treated with SMILE followed by autologous HSCT. Extranasal ENKL could be considered as a differential diagnosis when Dupuytren's contracture is suspected.

dupuytren contracture, lymphoma, extranodal nk-t-cell, tenosynovium

PMC5483351_01

Female

A 65-year-old woman, non-smoker presented with a two-month history of cough. She also complained of arthralgia and weight loss. The clinical examination revealed a febrile patient. The chest radiograph and the scanner revealed right upper lobar mass, with spiculated contours (A, B). Biology showed an inflammatory syndrome. Polymerase chain reaction for Mycobacterium tuberculosis and tumor markers was negative. A lung biopsy showed non caseous granulomatous vasculitis. The cytoplasmic antineutrophil cytoplasmic antibody (cANCA/PR3/ANCA) showed a positive result; Wegener's granulomatosis was finally confirmed. The patient was treated with prednisone and cyclophosphamide with favorable outcome. A follow-up chest radiography two weeks after treatment showed resolving pulmonary lesions (C).

anca, cough, granulomatosis with polyangiitis

PMC5658652_01

Male

A 69-year-old white man presented with a 5-week history of gradual onset of progressive abdominal distension. He did not report any other gastrointestinal symptoms and denied night sweats or recent travel abroad. His comorbid history included ischemic heart disease, with a myocardial infarction 11 years before this presentation. He was a former smoker, having quit 11 years ago (smoked 20 cigarettes per day for 35 years) and denied excessive alcohol intake or recreational drug use. His medications included an angiotensin-converting enzyme (ACE) inhibitor, a beta blocker, and a statin, all of which he had been taking for many years. He reported a family history of cancer, with 2 siblings deceased due to cancer of unknown origin. He had no history of previous blood transfusions, tattoos, or intravenous (IV) drug use. He was a farmer 20 years prior to presentation and had no exposure to asbestos. A clinical examination confirmed shifting dullness and the presence of ascites with no organomegaly. He had no peripheral stigmata of chronic liver disease, and the rest of the systemic examination was unremarkable. He had a normal complete blood count, clotting, liver function tests, liver screen serum ACE level, and urine analysis, and his renal function was moderately impaired (glomerular filtration rate 51 mL/min). Serum electrophoresis was normal, with a mild but not significant elevation in the immunoglobulin G4 (IgG4) subset. Macroscopic examination of the ascitic fluid revealed a milky color with elevated triglyceride levels consistent with chylous ascites. Microscopic analysis showed a cell count of 80% lymphocytes with no evidence of a bacterial peritonitis or tuberculosis. The transudate had a normal cytological examination. Ultrasonography confirmed a large volume of ascites with a normal liver and portal vein. An abdominal and pelvic computed tomography (CT) showed a mildly enhancing soft-tissue mass lesion encasing the mesenteric renal vessels and partly encasing the upper abdominal aorta, and the pancreas was involved as well (Figure 1). There as no overt involvement of the renal areas, but the left kidney appeared slightly enlarged, suggesting a degree of ureteric involvement, although the ureters were noted to be patent. These appearances were reported to be highly suggestive of a lymphoproliferative disorder with mass lesion. A completion CT staging did not reveal any evidence of lymphadenopathy or other pathology. Histology of a CT-guided biopsy confirmed a diagnosis of idiopathic RPF (Figure 2). Immunohistochemistry was normal and did not support Ig4 disease. The patient developed worsening renal failure during his hospital stay. A renal consult confirmed clinical intravascular fluid depletion, and IV fluids were commenced, resulting in an improvement in renal function. This confirmed a prerenal cause for the acute deterioration. Once his renal function started to improve, the rheumatologists suggested that he might benefit from corticosteroid therapy. This was mainly to prevent further progression of the inflammatory process of RPF and thereby slow or stop the advancement of obstruction and worsening of renal failure. He was given 3 pulsed doses of 500 mg IV methyl prednisolone. He was discharged and started on daily oral steroids, but the ascites rapidly reaccumulated and kidney function did not improve. Steroid therapy was discontinued. While he was on steroids, he was also started on azathioprine; this immunosuppressant was stopped due to intolerance. Since his discharge, large-volume paracentesis has been performed every 2-3 weeks for recurrent ascites. The patient currently awaits placement of an ascitic pump to allow home management.

PMC9191196_01

Male

We present a 40-year-old Gravida13 Para10 Abortion2 mother who presented with headache, epigastric pain, bilateral leg swelling, epistaxis, and decreased fetal movement for a two-day duration. Her previous pregnancies were uneventful with no prior history of hypertensive diseases in pregnancy or hyperthyroidism reported. Although she had eight home deliveries, there were no twin pregnancies or molar pregnancies. In addition, she had no family history of bleeding diathesis. On the current pregnancy, she had no bleeding, raised blood pressure or any danger signs on the antenatal follow-up she had at 9 weeks. She was referred from a local health center, where the diagnosis of co-existing molar pregnancy was overlooked, with the impression of twin pregnancy and pre-eclampsia. On admission, her blood pressure was 186/100, her pulse rate was 136 and her respiratory rate was 20. On abdominal examination, she had 36 weeks sized gravid uterus with fetal heartbeat of 136 and grade 2 bilateral pitting edema. On the admission blood tests, hematocrit was 32.8% with O+ blood type. Serum beta-HCG was found to be 215,400 IU/L, thyroid stimulating hormone was 0.05 IU/mL, urinalysis showed +1 proteinuria, other investigations (Renal function test, Liver function test, Complete blood count, and Chest X-ray) were all normal. With the impression of twin pregnancy complicated by pre-eclampsia with severity features and hyperthyroidism, the patient was managed for pre-eclampsia and a biophysical profile was done daily. Ultrasonography revealed two fetal sacs whereby twin A was a breech, alive twin with aggregate gestational age (AGA) of 28+6 weeks with the normal-appearing placenta as seen in (Figure 1). The other sac was filled with cystic spaces and snowstorm appearance, hinting towards a molar pregnancy (Figure 2). We managed our patient expectantly for a week with daily biophysical profile, dexamethasone injections for fetal lung maturity, magnesium sulphate and anti-hypertensive for pre-eclampsia. After one week, a cesarean section was done for indication of twin pregnancy plus Twin A breech to affect the delivery of a 1.4 kg male neonate with Apgar score of 7 and 9 in the 1st and 5th minute, respectively. The grape-like vesicles, separate from the normal appearing placenta, were evacuated manually (Figure 3). There was intraoperative bleeding while removing the molar tissue. Initial evaluation of the neonate revealed no congenital abnormalities and he was admitted to the neonatal intensive care unit with a diagnosis of very low birth weight and discharged after attaining adequate weight. Although, the histopathology result showed a partial mole with variable-sized dilated chorionic villi with focal trophoblastic proliferation and multiple vascular proliferation seen, there were no malignant features. Post-operative hematocrit was 18.8% for which the patient was transfused with one unit of whole blood. The patient was discharged from our side on the 16th day after advice on subsequent follow-up. The level of beta-HCG was determined to be normal on the 2nd follow-up at 7 weeks as illustrated in (Table 1). On this visit, the mother had no new compliant with normal blood pressure and TSH levels. In addition, the infant's interpretation of growth curves adjusted for gestational age showed adequate growth.

case report, partial mole, pre-eclampsia, twin pregnancy

PMC3445188_01

Female

A 17-year-old female elite high school junior basketball athlete (1.73 m, 66 kg, body mass index = 22.1 kg/m2) was involved in a collision during a basketball game, landing on her right hip. Her primary complaints were as follows: right lower back and groin pain, feeling like her back "popped," burning pain in the right anterior-superior thigh, and occasional catching/clicking in her right hip/buttock region. There were also complaints of pain (8 on a scale of 10) as a result of jogging the day before initial examination, an antalgic gait pattern on the involved right side, and pain with range of motion (ROM) of the lumbo-pelvic-hip complex. Due to the patient's acute pain level, she did not practice for the next week. The neurologic examination yielded negative results. The lumbar/pelvic girdle examination led to a focus on the hip joint (Figure 1). Hip strength was 3 (out of 5) for abduction and 4 for extension, compared to 4 for strengths on the left hip. Internal rotation ROM was 15 on the right and 30 on the left. Clinical testing for FAI and most labral tear tests yielded positive results. Right hip radiography, magnetic resonance imaging arthrogram (MRA), and 3-dimensional computed tomography suggested pincer impingement with cam lesion (Figure 2) and a tear of the superior labrum. Rehabilitation primarily addressed restricted hip internal rotation and hip/trunk weakness for 6 weeks, until surgical consultation. Intra-articular injection of 3 mL of Marcaine (bupivacaine hydrochloride) and 80 mg of Depo-Medrol (methylprednisolone acetate) was performed to confirm the diagnosis of intra-articular hip joint pathology. Complete (albeit temporary) relief of symptoms led to surgical consultation. Surgical intervention was recommended due to the recalcitrant nature of the patient's complaints, temporary complete relief of symptoms with intra-articular injection, as well as lack of significant improvement with physical therapy. At operation, the acetabular labrum was intact without pathologic pincer impingement. Articular cartilage breakdown of the anterolateral acetabulum was seen (grade III; Figure 3) with cam-type impingement. Chondroplasty of anterior acetabulum and synovectomy of acetabular fossa were performed, followed by femoroplasty for cam impingement. Initial rehabilitation consisted of controlled weightbearing with crutches (4 weeks), soft tissue mobilization, hip joint mobilizations (grades I and II), hip flexor and anterior/posterior hip joint stretching, progressive strengthening initiated with isometrics, and ROM in pain-free ranges. Once full weightbearing was well tolerated, exercises were slowly advanced to progressive resistive weightbearing, proprioceptive and balance exercises, and sport-related stretching and strengthening exercises. Hip mobilizations were progressed to grades III and IV for restricted ROM. A slow return to competitive basketball was allowed approximately 4 months after hip surgery. At the last clinic visit, 6 months after surgery, the patient scored 96 on the modified Harris Hip Score, had normal ROM and strength, and passed all functional testing. The patient was consulted via phone 20 months after surgery and was continuing with competitive basketball without complaints.

acetabular labral tear, hip arthroscopy, hip pain, low back pain

PMC2888849_01

Male

Roger is a 56-year-old man, fully right-handed (+100), with 16 years of education. All of his first-degree relatives are also fully right-handed. The original report of Roger's case was briefly described in a book chapter. The following report represents an extensive addition to the details contained within the initial case description. In previous studies, Roger was usually identified as "RH-1951." In this article, by written consent and preference of both the patient and his family, the name "Roger" was specifically chosen as the subject identifier and this name will continue to be used in future studies. Life for Roger began in 1952 with no health complications and no delays in achieving developmental milestones. Based on his parents' report, Roger lived a normal childhood, attained average grades throughout school, had a good social network of friends, and enjoyed playing sports, especially baseball and football. During his early teenage years, Roger developed insulin-dependent diabetes mellitus (Type 1 diabetes). He learned to adjust his lifestyle around his diabetes and his family reports that he has always effectively monitored his glucose levels, self-administered insulin, and maintained a strict diet. Following high school, Roger attended college and earned a BA in business administration. Uncertain of what career path to pursue, Roger spent his time enjoying outdoor activities. He was an avid skier and spent the winters helping with the day to day operations at a local ski resort. During the summers, Roger worked at Yellowstone National Park and spent much of his free time hiking and enjoying the tranquility of his surroundings. During this time period, Roger's family describes him as being a "friendly, easy-going guy" who was "quiet, reserved, and usually kept to himself." While at Yellowstone, Roger met a woman who motivated him to pursue a career capable of supporting a family. He enrolled in a manager training program and became an assistant manager for a large department store. A few months later, at the age of 28, Roger developed a high fever, nausea, and an intense headache. The emergency room physician sent him home with a diagnosis of influenza. When Roger failed to show up to work later in the week, his coworkers became worried and went to his apartment where they found him lying unconscious. He was rushed to the hospital where he was diagnosed with herpes simplex virus type 1 encephalitis and administered the antiviral agent vidarabine (ara-A). Roger's prognosis looked bleak and his family was told there was a strong likelihood he would not survive. After a nine day coma, Roger's condition stabilized and he slowly emerged from the coma, completely disoriented. A few weeks later he was discharged from the hospital with normal vision and hearing, sufficient strength and motor coordination, and a severe amnesia, anosmia, and ageusia. Since the encephalitic attack in 1980, Roger has literally lived another lifetime. However, for Roger, not much has changed over the past 28 years. He has virtually no episodic memories for any events which have transpired over the past three decades. For example, he has no recollection of 9/11 and when shown pictures of the planes crashing into the World Trade Center he often responds with bewilderment, speculating that Russia must be attacking America. At times, Roger confabulates, although his confabulations are generally non-bizarre and are usually provoked by memory-related questioning. He has no idea how many years have passed since the encephalitis, and when asked, his answers range from a few years to a few decades. His insight into his own condition is markedly impoverished. For example, Roger exhibits a complete anosognosia for his anosmia and ageusia. On occasion, only when directly asked, Roger might admit to having some problems with his memory. However, these problems are always downplayed and do not seem to disturb or upset him even though their severity has entirely precluded him from living an independent life and obtaining any sort of gainful employment. It could be said that he "doesn't remember that he doesn't remember." Up until 2003, Roger lived under the close supervision of his parents. Due to his parents' aging, he has moved into an assisted-care facility specialized for patients with brain injury. One element of Roger's behavior that must be closely supervised is his voracious appetite. Without monitoring, Roger will eat to the point of purging, showing no signs of satiation or fullness, and no memory for how much food has already been consumed. Interestingly, his appetite is still discriminative, as he will fastidiously avoid foods with high sugar content such as non-diet soft drinks and candy. Roger also has a compulsive tendency to collect objects of questionable value (e.g., matchbooks, pens, shiny metal objects, cottonballs, napkins, etc.) and hold onto them for no reason or particular purpose ( - subject AP1). During his free time, Roger frequently plays solitaire or listens to his extensive collection of 1960's rock n' roll vinyl albums (he has an impressive ability to hear a song from this time period and produce the name of the song, the name of the artist, as well as the name of the B-side song). He is also an excellent bowler and participates in a competitive weekly bowling league. Roger appears remarkably unconcerned by his condition. He hardly ever complains, and in general, shows little worry for anything in life. Both of his parents and his sister fervently claim that "Roger is always happy," an observation that is consistent with our own impression. Moreover, based on his family's report, Roger is paradoxically happier now than he was before his brain damage. This profound personality and affect change has also altered his social behavior. His premorbid disposition of being somewhat reserved and introverted has shifted to being outgoing and extraverted. In everyday life, Roger will often approach complete strangers, with no hesitation, and with no regard for social signals and contextual cues indicating otherwise. Consistent with these observations, Roger was found to rate pictures of complete strangers as significantly more trustworthy and approachable than healthy comparison participants ( - subject RH). During all social encounters, Roger has a strong proclivity towards jocularity and routinely recites jokes that are haphazardly handwritten in a notebook he keeps in his pocket. A quote found in this notebook has become Roger's life motto: "A good time to laugh is anytime you can." Roger is also a master of puns and has an uncanny ability to produce rich commentary about trivial aspects of his immediate environment. Indeed, a clinical psychologist who saw Roger in 1988 noted in his report that "Roger plays creatively and artistically with the nuances of language as if language was his toy." In many ways, Roger's loquacious speech and jocoseness is a form of vocal disinhibition, where his inner thoughts often appear to be freely spoken without a filter and without reflection. Roger's condition is stable. Since his referral to our laboratory in 1994, we have tested him on numerous occasions. Over the course of the past 14 years, we have not observed any changes in his personality or affect. Indeed, if it were not for his receding hairline, one would wonder whether Roger was aging at all. Roger's complacent and easy-going nature makes him a very pleasant and straightforward patient to test. He happily complies with all testing procedures, always puts forth his best effort, stays alert and attentive, and has excellent cognitive stamina.

PMC7438174_01

Female

Chest radiography was performed for a 7-year-old girl with persistent cough and fever who was unresponsive to oral antibiotics and showed loss of volume of left lung sustained by almost total atelectasis. The patient was then admitted to the pediatric ward to begin intravenous antibiotic therapy. Serological tests for Chlamydia pneumoniae , Mycoplasma pneumoniae , and QuantiFERON test for tuberculosis were negative. A computed tomography (CT) scan showed an extended mass that occupied the entire upper lobe with axial dimensions of 70 x 47 mm and assumed discreet enhancement in all the study phases. The bronchi for the upper lobe were no longer patent with endobronchial projection affecting the middle third of the main left bronchus. The mass caused posterior dislocation of the pulmonary arterial vascular axis and inferior dislocation of the superior pulmonary vein. Based on the radiological reports, the patient was referred to our pediatric surgery unit. To better define the characteristics of the lesion, a magnetic resonance imaging was performed. The pictures confirmed the presence of an expansive pulmonary lesion with a probable origin from the upper left lobe with transverse diameters of 57 x 45 mm and longitudinal extension of 85 mm. The lesion infiltrated the pulmonary hilum and invaded the bronchial structures up to the left main bronchus ~2 cm from the carina. It appeared adherent to the common trunk of the pulmonary artery and to the pericardium at the level of the left atrium and ventricle with infiltration of the superior pulmonary vein. The mass appeared to be surrounded by a thin rim of consolidated lung parenchyma; therefore, it does not seem to infiltrate the thoracic wall ( Fig. 1 ). For a complete diagnostic work-up, positron emission tomography-CT was performed; the findings showed softened uptake of the tracer at the voluminous expansive formation that tended to accentuate along the margins. Echocardiography revealed a 7-mm ostium secundum atrial defect with left to right shunt and deformity of the left ventricular cavity, with preserved systolic function. The deformity was attributable to the mass. All the tumor markers were negative. After multidisciplinary evaluation, ultrasonography-guided transthoracic core needle biopsy (22 Gauge) and bronchoscopic biopsies were performed to establish the diagnosis. Histopathologic examinations revealed the presence of medium-small-sized cells neoplasia, ovoid and plasmacytoid, with eosinophilic cytoplasm, lacking of evident cytological atypia with solid growth or in large nests alternating with myxoid and dense collagenous stroma. Immunohistochemical reactivity was positive for cytokeratine (CK) AE1AE3, p63, epithelial membrane antigen (EMA), S100, beta-catenin, SOX10, and terminal deoxynucleotidyl transferase (TDT). The morphological and immunophenotypic data were more suggestive of myoepithelioma. However, the immunocytochemical expression of TdT did not exclude the possibility of thymic neoplasm. Fluorescence in situ hybridization analysis showed the absence of translocation of FUS gene in 16p11, EWS gene in 22q12, and SS18 gene in 18q11.2. The case was discussed among pediatric surgeons, oncologists, and radiologists who concluded that the nature of the cancer was not sensitive to neoadjuvant treatment, thus indicating elective radical surgery. After the performance of sternotomy and opening of the pleura bilaterally, the left thoracic mass was revealed. The mass infiltrated the entire left lung and was attached to and infiltrated the pericardium, the left pulmonary artery and veins, as well as the left bronchus. We proceeded to release the left lower lobe by making selective distal ligation of the pulmonary arterial and venous vessels and of the left lobar bronchus. The lobectomy was completed with a mechanical stapler. The lower lobe appeared infiltrated by the mass at the level of the fissure. After resecting the lingular lobe, it was necessary to proceed under extracorporeal circulation to isolate the left pulmonary artery and veins. We isolated the pulmonary artery trunk as well as tied and dissected the Botallo's duct and the left branch of the pulmonary artery. The two left pulmonary veins and the main left bronchus were dissected and sutured. The mass was isolated from the remaining pericardium, from the vagus nerve, and from the phrenic nerve. Once the left pneumonectomy was completed and hemostasis was achieved, the interatrial defect was surgically closed, and a temporary pacemaker was implanted. A thoracic expander of 11 x 6 cm was applied and filled with 100 mL of saline solution. The expander reservoir connector was placed outside of the chest wall, and the reservoir was placed in a subcutaneous pocket. A left thoracic drain was placed dorsal to the expander. The postoperative course was uneventful. The temporary pacemaker was removed after 5 days, and the drain was removed after 8 days. The expander was gradually filled up to 200 mL with saline in three different infusions over 3 weeks ( Fig. 2 ). The patient was discharged on postoperative day 18. Histopathological analysis confirmed the presence of primary myoepithelial carcinoma of the lung (PMC-L) that infiltrated the bronchial wall up to the mucosa, the peribronchial fibroadipose tissue with vascular perineural-neural invasion, the pulmonary parenchyma, the visceral pleura, the pericardium, and a peribronchial lymph node with embolic metastasis. In view of the rarity of this neoplasm, the TREP group ("Rare Tumors in Pediatric Age") means rare tumors in pediatric age group was consulted to set up a plan for the follow-up care. The patient was then subjected to radiotherapy with rapid arc technique on the left thoracic wall in 34 diaphragmatic thickening fractions, 61.2 Gy in total. At the 14-month follow-up, the patient was alive and was breathing normally without oxygen support. Neither recurrence of PMC-L nor metastasis occurred, and no chest deformities were observed.

cancer, myoepithelial carcinoma, pediatric, pediatric surgery

PMC9909557_01

Female

A 54-year-old female patient presented with "irregular vaginal bleeding" in June 2021 without specific treatment. In November 2021, the patient visited our hospital with worsening vaginal bleeding symptoms for further treatment. She had menarche at the age of 14 years and menopause 6 years ago with previous cycles of 5-6 days/28 days with normal flow. No significant past or family history was reported. Vaginal examination showed a polypoid mass with a diameter of about 5 cm in the cervix and free parametrial tissue on both sides. Abdominal MRI showed that the cervix was obviously thickened, mainly on the posterior wall, with the thickest part being about 7.2 cm, and the lesion involved the upper vaginal segment downward. The myometrium is also obviously thickened. A vaginal tissue biopsy showed scattered heterogeneous cells, and combined with HE morphology and immunophenotype, mesenchymal-derived sarcoma was considered. The biopsy tissue tumor sample was small, so it was suggested to send further examination after complete excision for clarification. Immunohistochemistry of tumor cells was positive for EMA, P63, vimentin, desmin, SMA, Ki-67, ER, and caldesmon and negative for Ckpan (AE1/AE3), P40, actin, S100, MyoD1, myoglobin, and PR. In November 2021, she underwent "transabdominal tumor cytoreduction (total hysterectomy + right adnexal resection + greater omentectomy + pelvic lymph node [LN] dissection + para-aortic LN dissection) + pelvic adhesion release." When the uterus is cut open, a cervical tumor (5 cm x 4.5 cm x 4 cm) and uterine tumor (6.8 cm x 6 cm x 4 cm) were seen (Figure 1). Routine examination revealed the following diagnoses: (1) left internal iliac and foramen occulans LN 1/6, right deep femoral LN 1/10, and para-aortic LN 1/11, showing the characteristic of tumor metastasis from endometrial adenocarcinoma; (2) left external iliac LN 1, left total iliac LN 6, left deep femoral LN 5, right external iliac LN 1, right total iliac LN 3, and right internal iliac and foramen occulans LN 1, all showing reactive hyperplasia; and (3) large omentum, but did not show any cancer involvement. Postoperative pathological diagnoses are as follows: (1) the "body of the uterus" is a highly differentiated endometrioid adenocarcinoma (Figures 2D, F), infiltrating deep myometrium (> 1/2 layer), involving the cervical glands and interstitium, without definite nerve invasion or choroidal carcinoma embolism; immunohistochemistry is recommended for follow-up treatment. No definite tumor residue was seen in the vaginal section or the left and right parametrial sections. (2) No tumor involvement was seen in the right adnexa. The first supplementary report revealed a cervical tumor, combined with HE morphology and immunophenotype, and the lesion was consistent with carcinosarcoma (Figure 2B), a sarcomatous component with chondrogenic differentiation. Immunohistochemistry of tumor cells was positive for EMA (Figure 2C), S100, caldesmon, calponin, P16, MDM2, CDK4, CD99, ER, Brg-1 (SMARCA4), Ki67, CD10, and Fli-1 and negative for Ckpan (AE1/AE3), CK8/18, CK7, desmin, PAX-8, SMA, P40, actin, PR, NKX2.2, WT1, MyoD1, myogenin, SATB2, and ERG. The cervical and uterine body lesions were observed microscopically as two different tumor sites. Microscopically, endometrial adenocarcinoma and cervical carcinosarcoma collide at the cervix and show clear boundaries (Figures 2A, E, G, H). The FIGO stage was IIIc. Cycle 1 chemotherapy (paclitaxel 250 mg ivgtt d1 + carboplatin 500 mg ivgtt d1) was administered on 17 December 2021 and later administered doxorubicin 100 mg ivgtt d1 + carboplatin 300 mg ivgtt d1 in cycle 2 due to the patient's heavy treatment response. On 21 February 2022, the patient completed 28 external pelvic irradiation radiotherapy and 2 intracavitary backloading treatments. The patient continued with 3-6 cycles of chemotherapy (doxorubicin 100 mg ivgtt d1 + carboplatin 300 mg ivgtt d1). She remained healthy with no evidence of recurrence for 13 months after surgery.

cervical carcinosarcoma, collision tumor, endometrial adenocarcinoma, pathology, therapy

PMC3420530_01

Female

A 54-year-old woman was admitted to our hospital with fever, general malaise, and dyspnea. She had undergone bilateral breast augmentation surgery with silicone bags 5 years previously, with resurgery on the right side due to bag rupture 7 months before presentation. Seven days before admission, she became febrile and noticed dyspnea. She visited her family doctor and was diagnosed with pneumonia, but treatment with antibiotic therapy had no noticeable effect. She was then referred to our hospital for further examination and treatment. The patient was 158 cm tall, weighed 46 kg, and blood pressure was 100/50 mmHg, heart rate was 74 beats/min, body temperature was 37.0 C, and respiratory rate was 30 breaths/min on admission. Inspiratory rales were heard at both lung bases. The examination of the blood revealed severe thrombocytopenia with prolonged prothrombin time and high levels of fibrinogen degradation product (FDP) (Table 1). Chemical analysis revealed severe abnormal liver function with jaundice, mild renal insufficiency, and high C-reactive protein (CRP) level. Arterial blood gas levels on room air revealed hypoxemia with hypocapnia. All testing for autoantibodies yielded negative results. Blood culture was negative for bacteria. Computed tomography (CT) of the chest revealed nodular and macular shadowing in the right upper and middle lobes and left inferior lobe and ground-glass opacities in both inferior lobes (Figure 1(a)). Our patient saw an ophthalmologist, and there were no findings suggestive of uveitis. We diagnosed interstitial pneumonia with hepatic dysfunction and disseminated intravascular coagulation (DIC) and initiated methylprednisolone pulse therapy (1 g/day for 3 consecutive days) for interstitial pneumonia and gabexate mesilate and antithrombin III for DIC. Antibiotic (Meropenem trihydrate 1 g/day, Azithromycin hydrate 500 mg/day) was administrated to cover the possibility of concomitant bacterial pneumonia. On day 4, respiratory status and interstitial opacity on CT were improved (Figure 1(b)). However, fever recurred on day 10 and respiratory status and CT findings were deteriorated on day 15 (Figure 1(c)). Methylprednisolone (1 g/day for 3 consecutive days) was again administered, followed by prednisolone (40 mg/day) to avoid recurring exacerbation of interstitial pneumonia. On day 18, bronchoscopy was performed to identify the cause of interstitial pneumonia. Transbronchial lung biopsy specimens revealed small cell infiltrations of lymphocytes, plasma cells, and neutrophils. Analysis of bronchoalveolar lavage fluid (BALF) revealed an increased number of lymphocytes (52.5%) and a high CD4/CD8 ratio (2.52). However, the cause of interstitial pneumonia remained unclear. Ziehl-Neelsen staining of tissue samples and sputum culture yielded negative results for Mycobacterium tuberculosis. Fever recurred on day 20 and liver biopsy was performed to identify the cause of fever. We considered the possibility of sarcoidosis based on elevated levels of angiotensin-converting enzyme (ACE) (63.0 IU/L) and lysozyme (11.8 mg/mL). On day 23, Liver biopsy confirmed Langhans' giant cell and noncaseating granuloma (Figure 2(a)). On day 34, CT was performed to followup the interstitial pneumonia and fever, revealing miliary nodules in both lung fields, typical of miliary tuberculosis, although interstitial shadows had disappeared (Figure 1(d)). On day 35, antituberculosis therapy (isoniazid, 300 mg/day; rifampicin, 450 mg/day; ethambutol, 750 mg/day; pyrazinamide, 1200 mg/day) was applied for miliary tuberculosis after acid-fast bacilli were detected in gastric fluid and sputum, and polymerase chain reaction testing for Mycobacterium tuberculosis yielded positive results. Ziehl-Neelsen staining obtained positive results in a liver specimen (Figure 2(b)), but negative results in a lung specimen. Fever subsided following antituberculosis therapy. On day 41, rifampicin was stopped due to leukocytopenia (while blood cell (WBC) count, 1550/mm3; neutrophils, 350/mm3), likely caused by rifampicin. On day 59, the WBC count was fully recovered, and rifampicin was restarted at a low dose (150 mg). Fever was again seen on day 64, and CT was performed on day 68. Although miliary nodules in both lung fields had almost disappeared (Figure 4(b)), sickly shadowing was newly apparent in both upper lobes (Figure 4(c)). These new lesions were considered highly likely to represent recurrent interstitial pneumonia and not exacerbation of miliary tuberculosis, because exacerbation occurred during treatment for tuberculosis. On day 68, methylprednisolone was restarted at 0.5 g/day for 3 days and the dose of prednisolone was increased to 40 mg/day. Thereafter, fever subsided and the sickly shadowing had disappeared by day 72 (Figure 4(d)). On day 70, we switched from rifampicin to levofloxacin, as leucopenia had again progressed. Prednisolone was gradually tapered to 30 mg/day, and the patient was discharged without recurrence of the disease on day 100 (Figure 3).

PMC6222221_01

Male

A 39-year-old Thai male patient presented with progressive pain and swelling of seven-month duration over the antecubital fossa of the right elbow. Initially, there was only slight swelling. Three months later, he complained of dull pain. The patient went to a private clinic where the diagnosis was distal biceps tendinitis. The first doctor gave a local steroid injection, but the symptoms recurred about one month later. Four months later, the patient complained of pain at night and weakness on supination of the forearm and flexion of the elbow. He had no underlying disease, chest symptoms, fever, weight loss, or history of contact with patients suffering from pulmonary tuberculosis. Physical examination of the right elbow when patient visited the hospital in Thailand demonstrated swelling at the antecubital fossa, mild tenderness at the distal biceps, and muscle weakness or pain when attempting to supinate the forearm and flex the elbow. All other systemic examinations were normal. There was a high white blood cell count (12,710 cells/mcL); neutrophil count was 72% and lymphocyte count 17%. Erythrocyte sedimentation rate was 17 mm/hr, and C-reactive protein was 6.69 mg/L. Radiography of the right elbow showed swelling at the antecubital fossa, and chest radiographs showed infiltration of the left upper lung. Magnetic resonance images showed disruption of the distal biceps tendon with an associated ill-defined soft tissue mass (about 2 x 2 cm). A less enhanced area was observed at the inferior part, which was likely to be necrotic or cystic. An abnormal marrow signal was detected at the proximal radius with focal cortical erosion at the radial tuberosity (Figure 1). In this case, we suspected that the patient had disseminated tuberculosis because preoperative chest radiographs demonstrated left upper lung infiltration, which was likely pulmonary tuberculosis, and there was a soft tissue mass at the distal biceps tendon. We performed an open excisional biopsy and debridement using the single-incision anterior approach. The finding was a soft tissue mass involving the distal biceps tendon with complete tendon rupture. There was also a small focal cortical defect at the radial tuberosity. The ruptured distal biceps tendon was debrided. The tendon was repaired to the long-head tendon insertion, which was proximal to the focal defect by about 5 mm, using a TWINFIX Ti 2.8 mm Suture Anchor with one #2 ULTRABRAID Suture (Smith & Nephew Inc.). Antituberculosis chemotherapy started one day after the surgery, following a positive test of the fluid for acid-fast bacilli and a positive polymerase chain reaction for Mycobacterium tuberculosis. The patient received a total of 6 months of a rifampin-based regimen, which is recommended for musculoskeletal tuberculosis. The patient initially received isoniazid 300 mg, rifampicin 600 mg, ethambutol 800 mg, and pyrazinamide 1500 mg daily for two months and then reduced to isoniazid and rifampicin for the remaining four months. The elbow was immobilized in a posterior elbow slab with the forearm supinated for four weeks. Mycobacterium culture revealed Mycobacterium tuberculosis. Microscopic examination of the soft tissue revealed granulomatous inflammation with multinucleated Langhans giant cells and caseous necrosis. At the 1-year follow-up, erythrocyte sedimentation rate was 10 mm/hr, and C-reactive protein was 2 mg/L. Motor power of supination and flexion showed grade V and the hook test was negative. This study was approved by the Khon Kaen University Ethics Committee for Human Research (KKUEC) in which the study ID was HE611179.

PMC3341348_01

Male

The proband, patient II-4, presented at 13 years of age along with his 18 year old brother, patient II-2.The two brothers were the sons of first cousin Arab-Moslem parents of Palestinian origin (figure 3). The parents and three siblings were healthy. Pregnancy, delivery and early psychomotor development of the two patients was normal. On physical examination at 11 years, patient II-4 was first noted to have debilitating bradykinesia, rigidity, postural instability, hypomimia, and asymmetric tremor at rest. Therapeutic trials with Amantadine, Pramipexole, and L-Dopa did not provide any relief and the patient became wheel-chair bound at age 13. Despite being cognitively normal he could not attend school due to his physical impairment. Patient II-2 was reported to suffer from identical symptoms during childhood and had deteriorated to a dependent state by age 18. The course of his disease was more insidious with bradykinesia noted at 7 years and later appearance of rigidity, tremor and postural instability. The physical examination of both patients revealed hypomimia, slow and dysarthric speech, bradykinesis, pill-rolling tremor at rest, and postural instability with inability to walk. Glabellar tap was unextinguishable and no gaze paresis was elicited. In patient II-2 hypometric saccades were noted. Tone was increased in limbs with no spasticity, pyramidal signs or dystonia. Deep tendon reflexes were symmetric and normal. Plantar reflexes were downgoing. Fine alternating movements, finger and foot tapping were slow and reduced in amplitude. No cerebellar or sensory deficits were found. Brain Magnetic Resonance Imaging (MRI) was unremarkable in both patients. The parents, another brother and two sisters were healthy at ages 11 to 21 and had normal neurologic examinations. The study was approved by the Hadassah Institutional Review Board and the Ministry of Health. The parents consented to participate. Single nucleotide polymorphism (SNP) genotyping was performed in the DNA samples of the two patients and an unaffected brother, with the Affymetrix GeneChip Human Mapping 250 K Nsp Array as previously described. Homozygous regions larger than 2 Mb were manually searched. Selected SNP markers were used for genotyping the remaining family members. The carrier rate of the pathogenic mutation was determined by Sanger sequencing of the relevant exon in DNA samples of 133 anonymous ethnic matched controls. The DNA sample of patient II-2 was enriched for exonic sequences with the SureSelect Human All Exon v.2 Kit, which targets 44 Mb (Agilent, Santa Clara, CA, USA). Sequencing was carried out on a GAIIx (Illumina, San Diego, CA, USA) with 100-bp paired-end runs. Image analysis and base calling were performed with the Genome Analyzer Pipeline version 1.5 using default parameters. The sequence reads were aligned to human genome assembly hg18 (GRCh36) with DNAnexus software (Palo Alto, CA) using default parameters. Total RNA was isolated from fibroblasts of patient II-4 and from five normal unrelated adult controls, using Tri Reagent (Sigma). DNA traces were removed by treatment with TURBO DNAse kit (Ambion). RNA was reversed transcribed using Improm II kit (Ambion) and random hexamers primers. DNA concentration of two plasmids, one with an ACTB insert and the other with a cDNA insert encompassing exon 4 and 5 of DNAJC6, was determined by spectrophotometer. Serial dilution of the plasmids' DNA was performed in order to create a calibration curve on real time PCR instrument (ABI 7900). These calibration curves were used to determine the copy number of the respective transcripts in RNA samples from the patient and the controls. We used the concentration of the ACTB cDNA to normalize the concentration of the DNAJC6 cDNA and each sample was PCR four times. In order to study the endosomal system, transferrin uptake was measured in fibroblasts of patient II-2 as previously described with some modifications. Cells were incubated for 1 h at 37 C in labeling medium (F12 containing 10 mM HEPES, pH 7.3 and 0.2% w/v BSA) to remove unlabeled transferrin. They were then labeled for 1 h on ice with 50 microg/ml Alexa fluor 488-transferrin (Invitrogen) in labeling medium. After rinsing twice with warm labeling medium, they were incubated at 37 C for either 20 or 40 min to allow transferrin uptake. The cells were then fixed with 2% formaldehyde in PBS (RT, 30 min) and examined with a Zeiss Axiovert 200 microscope equipped with a 100x oil immersion objective. Online Mendelian Inheritance in Man (OMIM) http://www.omim.org/ SeattleSeq Annotation website - http://snp.gs.washington.edu/SeattleSeqAnnotation/ PolyPhen-2 prediction of functional effects of human nsSNPs http://coot.embl.de/PolyPhen/ SIFT - Sorting Tolerant From Intolerant http://sift.jcvi.org/ Mutation taster - http://www.mutationtaster.org/ NHLBI Exome Sequencing Project Exome Variant Server - http://evs.gs.washington.edu/EVS/.

PMC9771731_01

Male

The patient was a 2-month and 18-day old boy, who had experienced shortness of breath and feeding pause since birth. At the age of one and a half months, the shortness of breath became more obvious and the infant was cyanotic when feeding. The frequency of feeding pause and cough also increased, but no fever was noted. Nine days before admission, the patient was examined by chest computed tomography (CT) at a local hospital, with neoplastic lesions suspected in the right lung. Initially, the patient received oxygen therapy, amoxicillin-potassium clavulanate, and gamma globulin injection (400 mg/kg) because of an increased white blood cell (WBC) and C-reactive protein level (CRP). Four days later the patient was transferred to another hospital where he was treated with oxygen therapy and cefoperazone/sulbactam for 3 days. These treatments were not effective and the patient continued to experience shortness of breath and fever. He was transferred to our hospital with vital signs of T 38 C, P 172 beats/min, and R 42 breaths/min, as well as shortness of breath and signs of increased inspiratory load (e.g. three concave sign positive). As the condition progressed to respiratory distress and carbon dioxide retention, the infant was admitted to the pediatric intensive care unit (PICU) and received noninvasive ventilation immediately. For routine blood tests performed in other hospitals, all WBC counts were found to exceed the normal range, with a minimal value of 15.26 x 10 9/L and a maximal value of 34.1 x 10 9/L. In our hospital, WBC ranged from 17.31 x 10 9/L to 26.63 x 10 9/L. The concentrations of CRP and procalcitonin (PCT) upon admission were 34.99 mg/L and 0.21 ng/mL. Similarly, the (1, 3)-beta-D-glucan test (G test) initially showed a significantly high value of 177.2 pg/mL (cutoff value is 100 pg/mL). Initially, no pathogen was found in the sputum (by smear microscopy), blood, sputum, or BALF cultures. Other tests were also normal including immunoglobulin level, lymphocyte count, tuberculosis infection test (T-SPOT.TB), and cytomegalovirus IgM antibody levels. In the absence of evidence of pathogens, we can only choose empirical treatment. Despite this, the child was still short of breath and febrile. CT scans taken before treatment (Fig. 1A and B) showed inflammatory lesions in both lungs, along with a mass and incomplete expansion of the upper right lung. CT-guided lung puncture pathological examination was performed because of a suspected tumor. Pathological examination revealed granulomatous lesions in right lung tissue with a nodular structure and an infiltration of a large number of lymphocytes, plasma cells, neutrophils, and scattered multinucleated giant cells. Gram stain, AFB stain, Fite stain, and Silver stain excluded neoplastic lesions. Therefore, we performed fiberoptic bronchoscopy and BALF-mNGS examination. The location of the lesion was determined by chest imaging examination, and the most significant part of the lesion was selected for bronchoalveolar lavage. BALF of the child was collected according to Chinese Guidelines for Pediatric Flexible Bronchoscopy, the total "recovery time" should be >30%, and the "lavage time" should be controlled within 5 minutes. Nucleic acid was extracted from 5 mL of BALF followed by library construction and high-throughput sequencing performed with an Illumina Nextseq 550Dx sequencer. By sequence alignment, BALF mNGS identified A. fumigatus on day 10 (Fig. 2A) and day 28 (Fig. 2B). Prior to this, antibiotic treatment was ineffective. Combined with clinical manifestations, lung CT scan, lung puncture pathology, elevated G test value, all of which made us suspect a fungal infection. After Aspergillus was found, we immediately changed to targeted therapy with intravenous caspofungin, and the condition gradually improved, body temperature returned to normal and breathing improved. Two weeks later, it was changed to sequential oral therapy of voriconazole. The treatment process is outlined in (Fig. 3). Aspergillus is a common pathogen in people with immunodeficiency, so we have also improved the genetic testing. We found compound heterozygous mutations in the neutrophil cytosolic factor 1 gene (NCF1), consisting of a heterozygous mutation of paternal NCF1, and a deletion mutation of the maternal NCF1 that resulted in a large deletion of chromosomal segments (copy-number variations) of the gene (Fig. 4). The patient was diagnosed with autosomal recessive cytochrome b-positive CGD type I. The patient had oral voriconazole sequential therapy after discharge and remained in good condition through 3-months of follow-up. The CT scans showed inflammatory lesions in both lungs and incomplete expansion of the upper right lung, with significantly fewer lesions (Fig. 1C and D), without any symptoms of fever or shortness of breath.

aspergillus fumigatus, bronchoalveolar lavage fluid, case report, chronic granulomatous disease, metagenomic next-generation sequencing

PMC9638089_01

Male

A 53-year-old man fell down the stairs by accident and was hospitalized with TBI in the general ward of the neurology department at the Yaan Second People's Hospital. The swelling of his head and face was obvious, especially on the right side, and he had a typical left raccoon eye (Supplementary Figure 1). The brain computed tomography (CT) on admission showed two parts of abnormal increased signal in the bilateral temporal lobe and frontal lobe, and they might be confused with hemorrhage (Figures 1A,B). In addition, there was discontinuity, respectively, in the left orbital bone, the right cranial parietal bone, and the cranial temporal bone (Figures 1C-E). He was diagnosed with multiple injuries (the face, chest, and lower limbs), traumatic subarachnoid hemorrhage, bilateral frontotemporal lobe brain contusion, right temporoparietal and left orbital bone fractures, and right temporoparietal occipital scalp hematoma, right rib fracture, pulmonary contusion and multiple contusions of lower limbs. The patient was treated well-symptomatically and discharged more than 1 month later. The signal of the previous abnormal parts in the CT changed to low density, they might be manifestations of bleeding absorption (Figures 1F,G). However, pains persisted in the left forehead, especially a few days before the second hospitalization. During the previous month, the right limb occurred weakness twice, which continued for 5 min, but he did not go to hospital. Later, he complained that right limb weakness for more than 4 h and was admitted to our neurology ward at the Yaan People's Hospital. The patient's symptoms continued to worsen. Moreover, he responded slowly, and showed slurred speech, headache, and dizziness. There were no obvious symptoms of fever, dyspnea, gaze, or movement disturbance of other parts. He denied any history of hypertension, diabetes, hyperlipidemia, coronary heart disease, etc. His family had no other history of related diseases. The physical examination revealed his blood pressure of 150/85 mmHg, and a respiratory rate of 20 breaths per minute. The general condition of the patient was fair, and he had normal auscultatory findings of his heart and lungs. The other general physical examination was normal. The neurological examination showed that his eyes had sensitive to direct and indirect light reflex. However, the right nasolabial fold became shallow, and the tongue stuck out to the right. The neck was soft, the meningeal irritation sign was negative. In the physical movement examination, he could not hold objects with the right upper limb and could not stand and walk. The muscle strength of the right limb was grade 1, and the muscle strength of the left limb was grade 5. The pathological signs of the right side were positive. He had no limbs convulsions. No other focal neurological deficits were elicited. His ability of memory, calculation, time and space orientation all descended. He refused to do the other coordination movement examinations due to inconvenience. In the imaging examination, the brain CT displayed multiple pieces of decreased signal in the left cerebral hemisphere, this indicated the possibility of AIS (Figure 2A). The artery and angiography exhibited that the M1 segment of the left middle cerebral artery (LMCA) was partially interrupted, and distal blood flow reduced significantly (Figure 2B). The Alberta Stroke Program Early CT Score (ASPECTS) was 8. Moreover, the value of blood glucose was 8.26 mmol/L. The other tests showed normal generally, including the blood test, the biochemical test, the urine test, the stool test, the myocardial enzyme test, and the coagulation test. After completing various examinations, his National Institute of Health Stroke Scale (NIHSS) score was 13 and Modified Rankin Scale (MRS) score was grade 4. He had clear indications for emergency endovascular treatment and agreed with the interventional operation. The angiography showed there was dissection in the M1 segment of the LMCA (Figure 2C). The result showed that IAD was formed in the patient. He was operated on with balloon dilation and the self-expanding stent of the LMCA under general anesthesia. During the operation, the 3.5*20 mm intracranial self-expanding stent was released, and the LMCA was completely reanalyzed (Figure 2D). The patient was finally diagnosed with AIS and IAD (the M1 segment of the LMCA). The patient recovered well after surgery. Post-operative imaging showed no obvious abnormality, and the lesion gradually recovered (Supplementary Figures 2A,B). After 3 days, he was transferred to our general ward for rehabilitation. During treatment, he was given the aspirin tablet (100 mg once a day) and the clopidogrel tablet (75 mg once a day) to reduce the risk for progressive thrombosis, the atorvastatin tablet (20 mg once a day) to regulate lipid and stabilize plaque, the mannitol injection (125 ml once every 8 h) by intravenous and the furosemide injection (10 mg once every 12 h) to dehydrate and lower intracranial pressure. Subsequently, he requested to be discharged after the clinical symptoms were relieved (Supplementary Video 1), and his NIHSS score was 2 and MRS score was grade 0. Hereafter, we maintained telephone communication with him, and we asked him to take medication and rehabilitation on time. The patient is recovering well.

acute ischemic stroke, blunt cerebrovascular injuries, intracranial artery dissection, middle cerebral artery dissection, skull fractures

PMC5458075_01

Male

A 48-year-old man was admitted to our hospital due to prolonged fever and nausea. Physical examination indicated the following: Body temperature, 38.5 C; heart rate, 109 beats/min; blood pressure, 140/80 mmHg and lack of ausculatory sounds in the upper lobe of the left lung. Laboratory examination performed revealed: normal white blood cell count, 8.5 x 109/l, an elevated C reactive protein, 7mg/dl (0.01-0.8mg/dl) and negative tuberculosis antibody test. Computed tomography (CT) showed a large solid mass of the left upper lobe, limited pleural and pericardial effusion and calcified lymphadenopathy of mediastinum, Fig. 1. The patient underwent a CT-guided core biopsy of the lung lesion and three samples were obtained. Specimens were sent for culture, histological and polymerase chain reaction (PCR) assay. The possibility of malignancy was excluded, at the same time culture and PCR were positive for Histoplasma capsulatum and histological findings were compatible with BG, Fig. 2. Due to the positive culture we investigated patient's traveling history and he referred traveling in United States many years ago just for a few days. Complete laboratory investigation excluded any kind of immunosuppresion in our patient. The patient was diagnosed as a chronic pulmonary histoplasmosis case with bronchogenic granulomatosis. Initially he was treated with amphotericin B and itraconazole. One month later he revealed complete clinical recovery, improvement of the inflammatory index and decrease of solid mass size, nevertheless, pleural and pericardial effusions increased. Having in mind the histological diagnosis of bronchocentric granulomatosis and the aggravation of effusions, corticosteroids were added to the medication. Our patient was discharged two weeks later, in a good clinical status with itraconazole and methylprednisolone. CT imaging follow up one month later demonstrated a great decrease of the left lobe mass size. No pleural and pericardial effusion was reported Fig. 3.

bronchocentric granulomatosis, non endemic area, pulmonary histoplasmosis

a-b. CT image revealing large solid mass of the left upper lobe, limited pleural and pericardial effusion and calcified lymphadenopathy of mediastium.

PMC5458075_01

Male

A 48-year-old man was admitted to our hospital due to prolonged fever and nausea. Physical examination indicated the following: Body temperature, 38.5 C; heart rate, 109 beats/min; blood pressure, 140/80 mmHg and lack of ausculatory sounds in the upper lobe of the left lung. Laboratory examination performed revealed: normal white blood cell count, 8.5 x 109/l, an elevated C reactive protein, 7mg/dl (0.01-0.8mg/dl) and negative tuberculosis antibody test. Computed tomography (CT) showed a large solid mass of the left upper lobe, limited pleural and pericardial effusion and calcified lymphadenopathy of mediastinum, Fig. 1. The patient underwent a CT-guided core biopsy of the lung lesion and three samples were obtained. Specimens were sent for culture, histological and polymerase chain reaction (PCR) assay. The possibility of malignancy was excluded, at the same time culture and PCR were positive for Histoplasma capsulatum and histological findings were compatible with BG, Fig. 2. Due to the positive culture we investigated patient's traveling history and he referred traveling in United States many years ago just for a few days. Complete laboratory investigation excluded any kind of immunosuppresion in our patient. The patient was diagnosed as a chronic pulmonary histoplasmosis case with bronchogenic granulomatosis. Initially he was treated with amphotericin B and itraconazole. One month later he revealed complete clinical recovery, improvement of the inflammatory index and decrease of solid mass size, nevertheless, pleural and pericardial effusions increased. Having in mind the histological diagnosis of bronchocentric granulomatosis and the aggravation of effusions, corticosteroids were added to the medication. Our patient was discharged two weeks later, in a good clinical status with itraconazole and methylprednisolone. CT imaging follow up one month later demonstrated a great decrease of the left lobe mass size. No pleural and pericardial effusion was reported Fig. 3.

bronchocentric granulomatosis, non endemic area, pulmonary histoplasmosis

a-b. CT image revealing large solid mass of the left upper lobe, limited pleural and pericardial effusion and calcified lymphadenopathy of mediastium.

PMC5458075_01

Male

A 48-year-old man was admitted to our hospital due to prolonged fever and nausea. Physical examination indicated the following: Body temperature, 38.5 C; heart rate, 109 beats/min; blood pressure, 140/80 mmHg and lack of ausculatory sounds in the upper lobe of the left lung. Laboratory examination performed revealed: normal white blood cell count, 8.5 x 109/l, an elevated C reactive protein, 7mg/dl (0.01-0.8mg/dl) and negative tuberculosis antibody test. Computed tomography (CT) showed a large solid mass of the left upper lobe, limited pleural and pericardial effusion and calcified lymphadenopathy of mediastinum, Fig. 1. The patient underwent a CT-guided core biopsy of the lung lesion and three samples were obtained. Specimens were sent for culture, histological and polymerase chain reaction (PCR) assay. The possibility of malignancy was excluded, at the same time culture and PCR were positive for Histoplasma capsulatum and histological findings were compatible with BG, Fig. 2. Due to the positive culture we investigated patient's traveling history and he referred traveling in United States many years ago just for a few days. Complete laboratory investigation excluded any kind of immunosuppresion in our patient. The patient was diagnosed as a chronic pulmonary histoplasmosis case with bronchogenic granulomatosis. Initially he was treated with amphotericin B and itraconazole. One month later he revealed complete clinical recovery, improvement of the inflammatory index and decrease of solid mass size, nevertheless, pleural and pericardial effusions increased. Having in mind the histological diagnosis of bronchocentric granulomatosis and the aggravation of effusions, corticosteroids were added to the medication. Our patient was discharged two weeks later, in a good clinical status with itraconazole and methylprednisolone. CT imaging follow up one month later demonstrated a great decrease of the left lobe mass size. No pleural and pericardial effusion was reported Fig. 3.

bronchocentric granulomatosis, non endemic area, pulmonary histoplasmosis

a-b. Follow up with CT two months after treatment reveals great decrease of the lung lesion. None pleural and pericardial effusion is reported.

PMC5458075_01

Male

A 48-year-old man was admitted to our hospital due to prolonged fever and nausea. Physical examination indicated the following: Body temperature, 38.5 C; heart rate, 109 beats/min; blood pressure, 140/80 mmHg and lack of ausculatory sounds in the upper lobe of the left lung. Laboratory examination performed revealed: normal white blood cell count, 8.5 x 109/l, an elevated C reactive protein, 7mg/dl (0.01-0.8mg/dl) and negative tuberculosis antibody test. Computed tomography (CT) showed a large solid mass of the left upper lobe, limited pleural and pericardial effusion and calcified lymphadenopathy of mediastinum, Fig. 1. The patient underwent a CT-guided core biopsy of the lung lesion and three samples were obtained. Specimens were sent for culture, histological and polymerase chain reaction (PCR) assay. The possibility of malignancy was excluded, at the same time culture and PCR were positive for Histoplasma capsulatum and histological findings were compatible with BG, Fig. 2. Due to the positive culture we investigated patient's traveling history and he referred traveling in United States many years ago just for a few days. Complete laboratory investigation excluded any kind of immunosuppresion in our patient. The patient was diagnosed as a chronic pulmonary histoplasmosis case with bronchogenic granulomatosis. Initially he was treated with amphotericin B and itraconazole. One month later he revealed complete clinical recovery, improvement of the inflammatory index and decrease of solid mass size, nevertheless, pleural and pericardial effusions increased. Having in mind the histological diagnosis of bronchocentric granulomatosis and the aggravation of effusions, corticosteroids were added to the medication. Our patient was discharged two weeks later, in a good clinical status with itraconazole and methylprednisolone. CT imaging follow up one month later demonstrated a great decrease of the left lobe mass size. No pleural and pericardial effusion was reported Fig. 3.

bronchocentric granulomatosis, non endemic area, pulmonary histoplasmosis

a-b. Follow up with CT two months after treatment reveals great decrease of the lung lesion. None pleural and pericardial effusion is reported.

PMC8216370_01

Female

We present a 74-year-old, overweight woman with an extensive history with respect to her right knee. She had a right total knee replacement ("TKR") 2 years ago, followed by an open reduction and internal fixation ("ORIF") using a plate and screw construct after she had a fall, resulting in a periprosthetic fracture. The fixation failed and she underwent a revision of the TKR with a distal femoral replacement prosthesis. Her recovery was compromised by a chronic lateral patella dislocation. An extensor mechanism reconstruction and patelloplasty was successfully performed. The patient complained of right knee pain with weightbearing for the following 7 months. Eventually, the pain became unbearable, leading to a second revision to change the femoral component to a long-cemented stem. Her history of recurrent problems with her knee were suspicious for septic loosening of the femoral component due to an indolent prosthetic knee infection. She was treated empirically with Vancomycin while waiting for the culture results that came back negative despite the elevated CRP levels. No further follow up regarding her possible infection was recommended, and antibiotic administration was stopped since no positive culture confirmation was found. Three months later, she tripped and fell and sustained a Garden 4 subcapital fracture of the ipsilateral hip (Figure 1). Her co-morbidities consist of hypertension controlled with amlodipine with no end-organ damage, renal insufficiency, and obstructive sleep apnea supported by a continuous positive airway pressure ("CPAP") machine. She takes pregabalin to treat anxiety, olanzapine for bipolar disorder, fluoxetine for depression, and hydromorphone for pain relief. Upon admission, her physical examination revealed an externally rotated right lower extremity, normal neurovascular status distally, and a well healed midline surgical incision of the knee with bruising around the incision site. Her right lower extremity x-rays showed a long-cemented stem knee tumour prosthesis and a Garden 4 displaced subcapital fracture of the hip. Given that she was at high risk of developing avascular necrosis of the femoral head, open reduction internal fixation ("ORIF") would be unlikely to succeed, and a bipolar hip hemiarthroplasty would not have fit due to the long-cemented diaphyseal stem. Therefore, a TFR was performed.

non-oncologic, revision arthroplasty, salvage procedure, total femoral replacement, total hip arthroplasty, total knee arthroplasty

PMC8558788_01

Female

A 4-year-old girl with a history of eczema and absence seizures treated with ethosuximide presented with persistent fever, migratory joint pain, joint swelling, and hematuria. She was last at her baseline state of health 3 months prior to presentation, after which she experienced recurrent fevers and was hospitalized three times for pneumonia and impetigo. She then developed arthralgia, joint swelling, abdominal pain, fever, sore throat, cough, and change in behavior, prompting admission to a referring hospital. She was diagnosed with acute otitis media, started on ciprofloxacin, and transferred to our hospital for further management. At admission, her temperature was 37.5 C, heart rate was 115 beats/min, respiratory rate was 20 breaths/min, and blood pressure was 121/84 mmHg. She appeared uncomfortable and was "not herself" according to her mother. Physical examination revealed diffuse polyarthritis and tender generalized lymphadenopathy. There were no appreciable skin rashes, mucosal changes, cardiac murmurs, or pleurodynia. She did not have any history of travel outside the United States, toxic exposures, or contact with other sick children. Family history was significant for SLE in her paternal grandmother's sister. There was no family history of consanguinity. Admission laboratory studies were significant for anemia (hemoglobin 10.5 g/dL, range: 11.5-14.5 g/dL), elevated erythrocyte sedimentation rate (ESR; >145 mm/h, range: 0-20 mm/h), elevated C-reactive protein (1.12 mg/dL, range: 0.0-0.9 mg/dL), and a positive Direct Coombs test. White blood cell count (9.1 x 103/microL, range: 4.0-12 x 103/microL), platelets (267 x 103/microL, range: 150-450 x 103/microL), and thyroid-stimulating hormone (1.34 UIU/mL, range: 0.66-4.75 UIU/mL) were within normal limits. HIV and tuberculosis testing were negative. Urinalysis was notable for 30 mg/dL of protein as well as 15 red blood cells per high-power field. Quantitative urine protein-to-creatinine ratio was 1790 mg/g (nephrotic range > 3500 mg/g). The calcium-to-creatinine ratio was 0.07 (normal range <0.2). There was no microbial growth on urine cultures. Creatine kinase was within normal limits. Serum complement studies were notable for low C3 (48 mg/dL, range: 86-166) and low C4 (6 mg/dL, range: 9.7-36). C1q immune complex binding protein was high (61 mcg Eq/mL, range <= 25). She was also positive for both lupus anticoagulant and anticardiolipin antibodies. Recent outpatient rheumatology labs revealed an ESR of 77 mm/h, elevated antinuclear antibodies (ANA; >1:1280), as well as positive anti-double-stranded DNA (dsDNA), anti-Smith and anti-ribonucleoprotein antibodies. Unfortunately, her symptoms worsened before she could follow up on these results in clinic. Brain magnetic resonance imaging (MRI) with arterial and venous phase contrast was done due to abnormal behavior; no intracranial pathology or vascular abnormalities were present. Abdominal ultrasound revealed grade 2 pelviectasis in both kidneys, mild distension of the right renal pelvis, slight hepatomegaly, increased mesenteric echogenicity, trace pelvic free fluid, and no masses. A bone marrow biopsy:performed due to her arthralgias and lymphadenopathy:showed mildly hypocellular bone marrow with no blasts or other pathology. To further investigate the hematuria and proteinuria, a kidney biopsy was done, which revealed mild mesangial hypercellularity and immune complex membranous glomerulonephritis with full house IgM/C3-dominant staining on immunofluorescence and reticular aggregates on electron microscopy, consistent with Membranous Lupus Nephritis Class V (Figure 1).

rheumatology/clinical immunology, nephrology, pathology

PMC8428511_01

Female

A 46-year-old woman was diagnosed with right breast cancer (infiltrating ductal carcinoma, locally advanced) in April 2016. She underwent staging by positron emission tomography (PET) which revealed bilateral axillary, supraclavicular, hilar, and mediastinal lymph node metastasis and uptake in the left breast, bone, and several liver metastases with intense uptake in the pituitary. She was started with goserlin, letrazole, and denosumab. In June 2016, she started complaining of polydipsia. She was drinking more than 5 L of water per day. Magnetic resonance imaging (MRI) of the pituitary gland confirmed pituitary metastasis, and she exhibited signs and symptoms of pituitary insufficiency and diabetes insipidus. She was treated with suprasellar radiation therapy to the pituitary in July 2016 and maintained on replacement therapy mainly with levothyroxine, hydrocortisone, and desmopressin. She also had a small metastasis to the brain detected on MRI and was treated with gamma knife radiotherapy. In September 2016, follow-up PET showed marked improvement with near resolution of bone uptake, resolution of hepatic uptake, and decrease uptake in both breast lesions. In December 2016, repeated MRI of the brain showed re-demonstration of the previously depicted asymmetry of the pituitary gland being relatively and mildly more prominent on the right side with mild inclination of the pituitary stalk to the right. These findings are stable since the latest MRI. The previously depicted hyperintense small foci on tbl2 and fluid-attenuated inversion recovery sequences demonstrated a stationary course with no related edema, restricted diffusion, or abnormal enhancement. Moreover, in December 2016, PET showed hypermetabolic lesion in the right thyroid lobe for further correlation. Moderate hypermetabolic soft tissue lesion was noted in the right breast and required further evaluation. Nonfluorodeoxyglucose-avid multiple sclerotic lesions were observed at multiple levels of the thoracic and lumbar vertebrae. She maintained the same management, and follow-up imaging continued to show improvement. During this time, the patient was clinically well. In January 2018, follow-up PET showed clear progression of the disease with progressing neck and mediastinal lymph nodes, as well as right breast lesion and new bone lesions. At this time, the oncologist decided to start second-line treatment for premenopause as ribociclib plus fulvestrant and to continue gosrelin and denosumab. She continued to receive replacement therapy for panhypopituitarism. She responded well to treatment. In September 2018, the latest PET showed complete metabolic resolution of the disease (Figure 1).

diabetes insipidus, endocrine tumors, metastatic breast cancer, metastatic lung cancer, panhypopituitarism, pituitary

PMC8428511_02

Male

An 80-year-old man was referred to the endocrinology clinic for headache, thirst, and polyuria of 4 months duration. He was known to have hypertension, diverticulosis, and vitamin B12 deficiency. He drank at least 5 L of fluids per day. He also lost 6 kg of weight. He had no other systemic or alarming symptoms. On examination, he had normal visual fields and absence of cranial nerve palsy. He weighed 83.9 kg, and his body mass index was 28.4 kg/m. Clinical examination was unremarkable, with no features suggestive of acromegaly, Cushing's, or any other endocrinopathies. Results of baseline investigations were as follows: sodium of 147 mEq/L, plasma osmolality of 301 mosm/kg, prolactin of 1062 mU/L, and normal levels of other pituitary hormones. The water deprivation test showed results consistent with cranial diabetes insipidus. At baseline, his urine osmolality was 65 mosm/kg; after 2 h of water deprivation, it was 319 mosm/kg; and after subcutaneous administration of desmopressin, it increased to 416 mosm/kg. He was started with desmopressin and demonstrated good therapeutic response. MRI of the pituitary gland showed a 10-mm mixed cystic/soft tissue mass lesion filling the posterior aspect of the pituitary sella, with infiltration of the pituitary stalk (Figure 2). He continued to experience headache. Full-brain MRI confirmed the presence of a small nodule in each frontal lobe in addition to the pituitary mass lesion, likely metastatic deposits. Computed tomography (CT) of the chest, abdomen, and pelvis showed a central tumor of the right lung (CT stage tbl4), prominent para-aortic and left hilar lymph nodes, and metastatic deposit in tbl11. His general condition deteriorated very quickly, so he was not fit for palliative chemotherapy. He was referred to the palliative care team for symptom management. He died within 1 month of his diagnosis.

diabetes insipidus, endocrine tumors, metastatic breast cancer, metastatic lung cancer, panhypopituitarism, pituitary

PMC8428511_04

Female

A 70-year-old woman with metastatic right breast cancer (spinal metastasis) and autoimmune hypothyroidism was referred to the endocrine clinic for thirst and polyuria. She was on prednisolone 10 mg to enhance weight and well-being and letrozole. The oncologist ruled out diabetes mellitus and hypercalcemia. Clinical examination was unremarkable. Blood investigations revealed the following: normal sodium level, plasma osmolality of 296 mosm/kg, urine osmolality of 161 with low normal urine sodium, and elevated prolactin at 1051 mU/L. Cortisol was checked; however, it cannot be interpreted given her treatment with prednisolone. TSH was suppressed as she was on tbl3 replacement. The water deprivation tests confirmed the diagnosis of cranial diabetes insipidus. At baseline, her urine osmolality was 161 mosm/kg; after 4 h of water deprivation, it was 288 mosm/kg; and after subcutaneous injection of desmopressin, it further increased to 609 mosm/kg. She was started on Desmospray which immediately resolved her symptoms. MRI of the pituitary gland showed a 9-mm enhancing round lesion originating from the pituitary stalk impinging on the optic chiasm and optic tracts suggestive of metastasis (Figure 5). She received radiotherapy to tbl9 and the whole brain but developed sepsis during her hospital stay. She died 8 months later.

diabetes insipidus, endocrine tumors, metastatic breast cancer, metastatic lung cancer, panhypopituitarism, pituitary

PMC8428511_05

Male

A 50-year-old man presented to the hospital with a 3-week history of excessive thirst, urinary frequency, and right loin pain. He had felt generally unwell for the previous 8 weeks and had lost approximately 6 kg of weight over this time. He felt nauseous and had vomited several times. He urinated 4-5 times at night and had recorded a urine output of 3 L in 24 h at home. He had dull, right loin pain that did not radiate, was constant in nature, but exacerbated by movement. His appetite was grossly reduced. He was an ex-smoker [30 pack years]. On clinical examination, he was afebrile and normotensive. His heart rate was 70 beats per minute and regular. Results on admission were as follows: plasma osmolality of 289 mosmol/kg, urine osmolality (random) of 396 mosmol/kg, and urine sodium of 23 mmol/L. He was admitted into the hospital, and during hospital stay, he underwent an endocrine profile, with results shown in Table 1. His results were consistent with panhypopituitarism. He was commenced on hydrocortisone and subsequently felt much better. The nausea and vomiting stopped, and his 24-h urine output remained at 3 L. He presented again to the emergency department 4 days after discharge with worsening nausea and vomiting. He was unable to eat and could not tolerate his prescribed medications. He was given fluids, hydrocortisone, and antiemetic intravenously. Within 48 h, he felt well and was able to eat and drink normally; therefore, IV fluids were stopped. The dose of hydrocortisone was doubled for another 48 h and given orally. Levothyroxine and testosterone were also started. With further history assessment, he reported being unwell for more than a year, with excessive lethargy. He had decreased libido and was unable to maintain an erection. Examination revealed cervical lymphadenopathy that had not been present or recorded on previous examination. An in-patient MRI of the head was performed and showed "multiple ring enhancing lesions [>50], including a lesion in relation to the pituitary stalk measuring 8 mm. There was no associated mass effect or significant edema" (Figure 5). Chest X-ray imaging was performed and showed a left hilar mass. Urgent CT of the chest, abdomen, and pelvis was then arranged, which showed a large left upper lobe mass consistent with bronchogenic carcinoma. Lung, nodal, hepatic, and adrenal metastases were identified [CT staging tbl4, N3, M1]. Lymph node biopsy of a left cervical node was performed under ultrasound guidance. Histology confirmed a diagnosis of small cell carcinoma of the lung. He was commenced on dexamethasone (hydrocortisone was stopped) along with thyroid hormone and testosterone, but he died 2 weeks later.

diabetes insipidus, endocrine tumors, metastatic breast cancer, metastatic lung cancer, panhypopituitarism, pituitary

PMC8523104_01

Male

This case was a 70-year-old patient who had a history of atrial fibrillation (AF), symptomatic of dyspnea and congestive heart failure. At that time, his AF was converted by electrical cardioversion with resolution of his symptoms. A year later, he presented with several months' history of progressive and marked dyspnea with minimal exertion. He underwent regadenoson MPI for cardiac evaluation. His electrocardiogram (ECG) showed a normal sinus rhythm, first degree atrioventricular (AV) block, and T wave inversion in the inferolateral leads suggestive of myocardial ischemia (Figure 1). His MPI demonstrated mildly decreased LV ejection fraction of 49% without evidence of myocardial ischemia or infarction; however, significant LV calcification (Figure 2) was observed on the low-dose CT used for attenuation correction during MPI. Subsequently, other imaging studies, including chest x-ray, echocardiography, and chest CT, were obtained for further evaluation. The chest x-ray (Figure 3) showed extensive cardiac calcification, and the echocardiogram (Figure 4) revealed significant calcification of mitral valve annulus, LV septum, and mid free wall. However, his chest CT (Figure 5) revealed massive myocardial calcification involving only LV and its overlaying pericardium. The patient had no past history of malignancy, endocrine disorder, tuberculosis, or recent traveling to other countries. Extensive laboratory evaluation revealed elevated NT-proB-type Natriuertic Peptide (1113.5 pg/ml; normal < 100 pg/ml) and C-reactive protein (1.21 mg/ dL, normal < 0.5 mg/dL), but normal findings of complete blood count, basic chemistry profile, troponin-I, sedimentation rate, antinuclear antibody, antimitochondrial antibody, serum calcium/phosphate level, vitamin D level, and thyroid and parathyroid hormone levels. His echocardiography showed: (1) normal LV systolic function with calcification in the LV septum, mid free wall and mitral valve annulus (Figure 4) and normal right ventricular (RV) size and systolic function; (2) moderate bi-atrial enlargement with mild mitral regurgitation, moderate tricuspid regurgitation; and (3) severe pulmonary hypertension and LV diastolic dysfunction. Cardiac catheterization demonstrated: (1) no angiographic evidence of coronary artery disease; (2) moderately severe pulmonary hypertension with pulmonary artery systolic pressure of 67 mmHg; (3) elevated pulmonary capillary wedge pressure, measured at 28 mmHg; (4) elevated LV end-diastolic pressure, measured 29 mmHg; and (5) no evidence of ventricular interdependence on simultaneous LV/RV pressure measurement. The final diagnosis was congestive diastolic heart failure due to massive LV myocardial calcification of unknown etiology. He was treated with aggressive diuresis and other guideline-driven medical therapy successfully with marked improvement of his dyspnea on exertion during follow-up.

spect ct, incidental findings, myocardial perfusion imaging, vascular calcification

PMC6815478_02

Male

A 70 year old man smoker was admitted to the emergency unit of the military hospital, with a history of progressive dyspnea during two weeks, and with increase of the abdominal volume and diffuse oedema of the lower limb, giving a rise to a clinical diagnosis of heart failure. He had no fever and no weight loss. His past medical history included HTA without treatment, and without diabetes or tuberculosis. On clinical examination, vesicular breath sound was diminished in right hemithorax, blood pressure was 15/10. An ECG showed sinus rhythm and left ventricle hypertrophia. An echocardiogram revealed normal function of both ventricles. Chest radiographs showed large pleural effusion (Figure 1). At right punction, approximately 3 liters of bloody fluid was drained. A CT-scan of the chest was performed and confirmed the severity of effusion, particularly in the right hemithorax, and a prominent thickening of right pleura with basilar atelectasis. Hilar and mediastinal lymphadenopathy were identified without evidence of tumor lesions in other organs (Figure 2). The cytological study of pleural effusion did not reveal any definit results. A fibroscopy was performed and multiple biopsies were taken from the parietal pleura. On macroscopic examination, the received sample of pleural tissue matched with a red brown tissue of 0.4x0.3x0.2cm. The sample received was fixed with 10% buffered-formalin and stained with the hematoxilen and eosine(HE) after paraffin-embedded sections. Imunohistochemical stains have been performed on serial paraffin sections of 5u mounted on precoated slides and followed by deparrafinization using the following antibodies: TTF1, calretinin, CKAE1/AE3, Ck5/6, CD3, CD20, CD31, CD 34, FVIII-related antigens, EMA, MPO, MELAN A, HMB45, HMBE1. Histologically, it was a neoplastic proliferation consisting of large atypical epitheloid cells with abundant amphophilic cytoplasm. A marked nuclear polymorphism was observed and the nuclei showed a single prominent nucleoli and vesicular chromatine. The mitotic index was 10 per 10HPF. Intratumoral lymphocyte infiltrate was rather scanty (Figure 3). This morphological aspect was suggestive of some diagnosis, especially a pulmonary epidermoid carcinoma, a mesothelioma and even adenocarcinoma. Therefore need for immunohistochemistry was mandatory to provide an accurate diagnosis. The abovementioned antibodies were used following the diagnostic hypotesis step by step. In addition, the vasoformative pattern guided us to perform vascular markers (Table 1). Immunohistochemical analysis showed strong positivity of tumor cells for endothelial markers: CD31 and the Factor VIII-related antigens. The CD 34 was negative. The tumor cells showed focal staining for EMA and for CKAE1/AE3. They were negative for HMBE1, CK5/6, HMB45, MELAN A, calretinin, CD3, CD20, MPO, and AML (Figure 4, Figure 5). The overall pathological immunohistochemical features supported the diagnosis of a malignant epitheloid vascular tumor consistent with epitheloid.

angiosarcoma, pleura, epitheloid, immunohistochemistry

CT-scan showing a prominent thickening of the right pleura.

PMC8097037_01

Male

A 40-year-old man presented with intermittent headache and diplopia. 6 years before admission, he had recurrent headache at top and frontal area. He had been diagnosed with tubercular meningitis in the local hospital and received HRZE regimen for 2 months followed by HRE regimen for 27 months. His headache was not alleviated and then he went to our hospital 3 years ago. Contrast-enhanced magnetic resonance imaging (MRI) demonstrated an enhancing mass overlying clivus with dural tail sign. The lesion was initially considered to be a meningioma based on its imaging appearance. The patient then received a gamma knife surgery. The headache mitigated a little but persisted to date. 7 months before returning to our institution, he developed diplopia, hoarseness, and dysphagia progressively. On examination, the patient had bitemporal hemianopsia and limited abduction of both eyes (Figure 1A, upper). He had no speech disturbance or motor dysfunction. Contrast-enhancing MRI showed a 3.8x2.9x2.9 cm mass overlying clivus with dural tail sign (Figure 1A, lower). The lesion oppresses brain stem, with bone erosion at the clivus and left talus cone region and part of the lesion protrudes into pharyngonasal cavity. Cerebrospinal fluid examination was generally normal and mycobacterium spp. and cryptococcus were not detected. He received a surgery with endoscope removing mass subtotally. The histopathological evaluation revealed fibro-connective tissue with mixed inflammation containing predominantly plasma cells. Immunostaining showed increased number of IgG4-positive plasma cells (>200/HPF) and elevated ratio of IgG4-positive cells to CD138-positive cells (approximately 55%, Figure 1C). No granuloma with caseous necrosis was noted. These findings were suggestive of an IgG4-RD and the patient was transferred to our department. Immunoglobulin analysis revealed IgG 17.2 g/L (normal range 8.0-15.5 g/L), IgG4 subclass 1.9 g/L (normal range 0.035~1.5 g/L). Serum levels of IgA, IgM, C3, and C4 were normal. Antinuclear antibody revealed 1:100 titer, while anti-neutrophil cytoplasmic antibodies, anti-SS-A, anti-SS-B, anti-dsDNA, anti-Smith, anti-Scl-70 as well as other anti-ENA were all negative. HCV antibody, HBV surface antigen and HBV-DNA were negative. TST was positive (induration >=10mm) and TB-IGRA demonstrated significantly elevated IFN-gamma (414.21 pg/ml, normal range 0-14 pg/ml). Repeated sputum tests were negative. A computed tomography scan of her chest showed neither lung lesions suggestive of TB nor hilar or mediastinal lymph node swelling. Investigation of other systemic manifestation of IgG4-RD was negative. We diagnosed the patient with IgG4-RD complicated with LTBI. Treatment of corticosteroids combined with methotrexate (10mg/week) and cyclophosphamide (0.5g/m2/month for 3 months) was initiated and was well tolerated by the patient. Isoniazid was also started to prevent TB recurrence. In a follow-up of 3 months, he had attenuated bitemporal hemianopsia and better abduction of both eyes, and MRI showed the clivus mass shrank remarkably (Figure 1B). Serum IgG consecutively decreased to 8g/L and became stable, while IgG4 level decreased to between 0.4-0.6 g/L along 9 months follow-up (Figure 1D). In addition, the patient did not complain any TB related syndromes and the IFN-gamma level in the TB-IGRA test decreased gradually (Figure 1E). The cause of IgG4-RD remains unclear, however, chronic infection such as TB was reported in IgG4-RD (summarized in Table 1). Notably, IgG4-RD occurs either after TB contact or diagnosis, or at the same time as TB confirmation. Among those patients, TB occurs in lung, urinary tract, lymph node and meninges. China has always been one of the countries with the most serious TB epidemic all over the world. In 2017, about 60.08/100'000 cases of TB were reported in China. In addition, skin test positivity ranged from 15% to 42%, and IGRA positivity rate ranged from 13% to 20% in rural China. TB is closely related to patients with rheumatic diseases who are receiving immunosuppressive therapies, however, TB incidence in IgG4-RD patients remains unknown. We performed an additional retrospective study to explore the frequency of TB infection in IgG4-RD patients at our institute (Supplementary Figure S1). According to the 2011 comprehensive diagnostic criteria, we identified 83 subjects with a diagnosis of IgG4-RD who visited our hospital between February 2015 and September 2020. Among them, 47 were screened for TB infection. In 17/47 (36.2%) patient with IgG4-RD, a TB disease (positive signs of TB disease symptoms and chest computed tomography and positive TB tests) or LTBI diagnosis (negative signs of TB diseases and chest computed tomography (CT), M. tb was not isolated from a clinical specimen, but positive TB-IGRA and/or TST) was present (Supplementary Figure S1). Among the 17 subjects, 82.4% were male and the median age is 52.5 +- 14.3 years. Except two patients (No. 4 and 7), all other patients had high levels of IgG4 in the serum. Two patients (No. 2 and 15) had TB disease based on positive TB symptoms, chest CT, and TB blood test/TST, while others had LTBI. Organ involvement, laboratory examinations, and diagnosis in these patients are summarized in Table 2.

ifn-gamma release assay, igg4-related disease, intracranial, retrospective cohort, tuberculosis

PMC7519964_01

Male

A 6-year-old boy presented to our paediatric assessment unit for evaluation of persistent mutism following a hospital visit for routine venepuncture. He had been non-verbal for a few weeks and had begun using an iPad "talking board", at which he pointed to pictures and words. Due to this persistent mutism he had stopped attending school and it became clear there had been a sudden behavioural change. He was born at term following an uneventful pregnancy to a single mother with mental health disorder. He has two younger brothers who have no history of developmental disorder. Prior to this presentation, he maintained a weight and height above the 25th centile. Apart from language delay he met his early developmental milestones. He attended nursery from age three and was assessed by age five for possible autism by the local child and adolescent mental health service (CAMHS). Although some of his behaviours appeared autistic in nature he did not meet the diagnostic threshold for ASD as he was functioning comparatively well in his first year of school. Six months after the earlier presentation with mutism, he was found lying on the floor, still and unresponsive with no clear trigger identified. Further episodes occurred and each lasted between a few minutes and two hours. During these episodes he would not speak, move, or respond to vocal or touch stimuli. These episodes would end as abruptly as they started with him sitting bolt upright, being reactive, and crying. Subsequently, these catatonic episodes became more frequent and prolonged, lasting between ten and 48 hours. His weight dropped from the 25th centile to the 0.4th centile. This required admission to the local paediatric ward and a nasogastric tube (NGT) was inserted for nutrition and fluids. There was an initial difficulty in establishing a feeding regime, as he would frequently vomit. Eventually, a slow overnight feed was sufficiently tolerated. Whilst on the paediatric ward any catatonic episodes were preceded by extreme agitation, usually prior to a procedure such as passage of a NGT or venepuncture, and when ward staff attempted to restrain him he would suddenly become limp and unresponsive. He was also observed to lick and sniff ward staff that he liked and would frequently remove his NGT and offer it to staff as a gift. He became a significant flight risk with no sense of danger, requiring a wheelchair with restraining straps to attend appointments with his mother. He was assessed by the paediatric neurologist and had extensive neuro-metabolic blood investigations, an electroencephalogram (EEG), and magnetic resonance imaging (MRI) of his brain (Figure 1). These were essentially normal. He was trialled on lorazepam with a good response and an immediate reversal of his catatonia. Nevertheless, catatonic episodes continued in the absence of lorazepam and he was therefore transferred to the National Child Psychiatric Inpatient Unit (NCPIU) for five weeks for further assessment outside of his normal environment. He was commenced on regular lorazepam and his clinical condition improved significantly, with no further catatonic episodes during this admission. He was diagnosed with ASD with co-morbid catatonia because, now aged 7, he had been withdrawn from school by his mother and his social communication skills had regressed to the point he now satisfied the DSM 5 criteria for a diagnosis of ASD. Autistic symptoms (though not satisfying the DSM 5 criteria) had been present for two years prior to the development of catatonia. On discharge from the NCIPU he struggled with transition to life at home. He developed stress-related alopecia and the frequency of catatonic episodes increased significantly. Atomoxetine was commenced following a diagnosis of co-morbid attention deficit hyperactivity disorder (ADHD). This was diagnosed on the basis of the DSM 5 criteria; he displayed a persistent pattern of inattention and hyperactivity-impulsivity that interfered with his functioning and development. Atomoxetine was soon stopped, however, due to nausea and vomiting. The lorazepam was increased to a maximum of 12 mg (0.54 mg/kg) daily which resolved his catatonic episodes. Guanfacine was commenced but soon withdrawn as the patient refused to swallow it. Methylphenidate was started and has been titrated to 15 mg twice daily which has been effective (decreasing emotional outbursts, increasing creative play and ability to self-soothe) and well tolerated with no adverse effects. Lorazepam 12 mg daily was well tolerated with no adverse effects. It has since been decreased to dose of 8 mg daily with plans to wean further.

autism, catatonia, child, lorazepam

PMC8217822_01

Male

A 54-year-old man with no smoking history presented with persistent cough in January 2011. Thoracic computed tomography (CT) demonstrated a pulmonary left lower lobe mass. The patient underwent a left lower lobectomy with mediastinal lymph node dissection. The tumor size was 4.0 x 3.5 x 3.5 cm with no lymph node metastasis (pT2aN0M0) and was histologically diagnosed as an adenocarcinoma. No adjuvant chemotherapy or radiotherapy was performed. Two years after the operation, metastasis in the right femoral head was detected by magnetic resonance imaging (MRI) ( Figure 1A ). A deletion at exon 19 of the EGFR gene was identified by Sanger sequencing in a surgical specimen of the primary lung carcinoma. The patient started radiotherapy for the right femoral head metastasis followed by gefitinib treatment with 250 mg/day in December 2013 and showed a partial response. Mediastinal lymphadenopathy was detected by CT in December 2017 ( Figure 1B ). There was no disease progression to other sites. The patient refused endobronchial ultrasound-guided needle aspiration (EBUS-TBNA) of the mediastinal masses. Given the absence of EGFR T790M mutation detection in the liquid biopsy sample, he continued with gefitinib treatment and received radiotherapy for the mediastinal lymph nodes in January 2018. A partial response was achieved. Disease progression was revealed by CT showing a metastasis in the left adrenal gland in August 2020 ( Figure 1C ). The patient then received treatment with the third-generation EGFR-TKI almonertinib at 110 mg/day in August 2020 and showed stable disease. Left adrenalectomy was performed in October 2020. Squamous cell carcinoma histology was identified from the left adrenal gland specimen by immunohistochemistry, which was TTF-1 and NapsinA negative, P40 partially positive, and CK7 positive ( Figures 2A-C ). The sample was subjected to a sequencing study using FoundationOne CDx (an FDA-approved 324-gene panel assay), and the results showed an EGFR exon 19 deletion (delE746_A750, allele frequency [AF]: 26.68%). Histopathological re-examination of the surgical sample from the resected primary lung carcinoma revealed adenocarcinoma with partial squamous differentiation (less than 5%), which was partially positive for TTF-1, NapsinA, and CK5/6, focally positive for P40, and CK7 positive ( Figures 2D-F ). Sequencing results of the initial lung specimen demonstrated the same EGFR 19del (delE746_A750, AF: 80.37%) and EGFR amplification (copy number [CN]: 30). The timeline illustrating this patient's medical history and treatment is presented in Figure 3 . The patient is currently continuing almonertinib monotherapy and the disease is stable.

egfr amplification, egfr mutation, histological transformation, lung adenocarcinoma, resistance to gefitinib, targeted therapy

PMC4532079_01

Female

A 54-year-old woman was admitted to the hospital in May 1992 with a chief complaint of diffuse abdominal pain for a duration of one week. She had been treated with CAPD since January 1992 for end-stage renal disease of unknown etiology. One week before admission, the patient developed diffuse abdominal pain, fever and chill and she was treated with intraperitoneal cefazolin and tobramycin for six days at the out-patient department. At that time, the peritoneal fluid contained 2,250 leukocytes per mm3 with 85% polymorphonuclear cells, and routine culture yielded no organisms. In spite of six days' antibiotics therapy, there was no improvement. The temperature was 37.8 C, the pulse rate was 87 per minute and the respirations were 25 per minute. The blood pressure was 140/90 mmHg. On physical examination, the patient was alert and appeared acutely ill. Examination of the head and neck was normal, except for pale conjunctiva. The heart and lungs were normal. The abdomen was rigid and diffusely tender but the catheter exit site showed no signs of infection or leakage; the liver and spleen were not palpable. There was peripheral edema. The peripheral leukocyte count was 9,000/mm3, with 88% neutrophils, 8% lymphocytes, 4% monocytes and hemoglobin was 7.5 g%. Her serum sodium was 137 mEq/L, potassium 4.2 mEq/L, chloride 106 mEq/L, calcium 8.3 mEq/L, phosphate 2.7 mEq/L, urea nitrogen 27 mg/dl and creatinine 6.2 mg/dl. Serum total protein was 6.0 g/dl, albumin 2.9 g/dl, total bilirubin 0.3 mg/dl, aspartate aminotransferase 17 IU/L, alanine aminotransferase 3 IU/L and alkaline phosphatase 39 IU/L. X-ray films of the chest and abdomen were normal. The peritoneal fluid was cloudy and contained 1,000 leukocytes per mm3, with 90% polymorphonuclear cells. Intraperitoneal ceftizoxime and amikacin were administered after routine culturing of the peritoneal fluid was done. Initial gram and acid-fast staining revealed no organisms and routine cultures showed no growth. Abdominal pain was persistent and routine cultures again showed no growth, but follow-up acid-fast staining was reported to be positive. Therefore, cultures for mycobacteria were requested repeatedly. Antibiotics were discontinued and antituberculous drugs (isoniazid, rifampin, ethambutol and streptomycin) were begun. The peritoneal catheter was surgically removed and hemodialysis was begun. Atypical mycobacteria, not Mycobacterium fortuitum, grew three times after 2 weeks of incubation periods. Colonies of atypical mycobacteria were sent to Korean Institute of Tuberculosis, Korean National Tuberculosis Association for identification and susceptibility tests, and they were identified as M. fortuitum. The results of the identification test are given in Table 1. The result of susceptibility test against antituberculous drugs showed "all resistance". Test against antimicrobial agents was not performed. Empiric therapy with intravenous use of ceftizoxime and amikacin was started and the patient improved. Until now, she has done well on hemodialysis.

PMC5483369_01

Female

A 70 year old female presented with a 4 months history of dyspnea, weight loss and fever. The physical examination revealed icterus, multiple lymphadenopathies, hepatomegaly, jugular venous distension and a 2/6 diastolic heart murmur. Laboratory evaluation showed a moderate inflamatory syndrome, cytolysis and negative hemocultures. CT revealed multiple mediastinal and mesenteric lymphadenopathies, segmental thickening of colic wall and ascites. The PPD skin test was positive at 13 mm. The histopathological study of a lymphadenopathy biopsy was compatible with caseum. Quantiferon-TB test was highly positive. HIV serology was negative. A cardiac echocardiography revealed a 28 x 28 mm masse located at the anterior mitral valve (A, B, C, D) fusing to the mitro-aortic junction and along the proximal aortic wall (E, F). The masse was partially drained at left valsalva sinus (G, H). There was a moderate aortic insufficiency (I). The diagnosis of ganglionar tuberculosis with endocadiac and aortic involvement was highly suggested according to clinical, epidemiologic, biologic arguments. The patient was given antituberculosis drugs for 9 months with a spectacular clinical improvement with no regression of the abcess. She is scheduled for surgical treatment.

mycobacterium tuberculosis, endocarditis, native valves

PMC8486939_01

Female

Patient information: a 74-year-old female presented with persistent heartburn, acid reflux and up to 6 non-bloody loose stools per day. Her bowel movements were painless and unaffected by fasting or diet. She also reported bloating, flatulence, difficulty swallowing and unintentional weight loss of 17 kilograms. She was euglycemic, and her regular medication included telmisartan and amlodipine for blood pressure control. Clinical findings: her vital signs were unremarkable, and she was cachexic with taut hyperpigmented skin on her face. She had a distended soft non-tender abdomen with no palpable masses. Diagnostic assessment: laboratory tests showed mild microcytic anaemia and loose stools with pus cells. Stool studies for parasites, occult blood, elastase and faecal fat were all normal. Antinuclear antibody (ANA) was positive with a titre of 1: 320, and extractable nuclear antigen was positive for nRNP/Sm and SSA antibodies. Serum amylase, tissue transglutaminase antibody, anti-liver kidney microsomal antibody, anti-smooth muscle antibody and antimitochondrial antibody were normal. Barium swallow demonstrated proximal oesophageal dilatation with delayed emptying (Figure 1). A chest computed tomography (CT) scan showed the usual interstitial pneumonitis pattern of scleroderma-related lung disease. Abdominopelvic CT scans revealed luminal dilatation of the oesophagus, stomach, small and large bowel, as well as faecal loading (Figure 2). No cause of mechanical obstruction was identified. An upper endoscopy showed proximal oesophageal dilatation with distal oesophagitis and narrowing (Figure 3). Biopsies of the distal oesophagitis were mild non-specific chronic inflammation on histology, in keeping with gastro-oesophageal reflux disease (GORD), whereas duodenal biopsies revealed normal mucosa. There was no gross or histological evidence of malignancy, coeliac disease or telangiectasia. Capsule endoscopy revealed significant oesophageal dysmotility, with the capsule taking more than 5 hours to traverse the oesophagus despite administration of intravenous metoclopramide. Distal oesophagitis with ulceration was seen, and a significant amount of food was in the stomach despite overnight fasting, suggestive of gastroparesis (Figure 4(A, B)). Therapeutic intervention: she was treated with antibiotics and rabeprazole/domperidone combination capsules for small intestinal bacterial overgrowth (SIBO) and dysmotility and reported marked improvement in her symptoms. She was then started on mycophenolate mofetil. Follow-up and outcomes: the patient reported marked improvement in her symptoms with resolution of the loose stools, dysphagia and reflux, and she has monthly follow-ups in our clinic with monitoring of haemoglobin and inflammatory markers. Her long-term maintenance therapy includes regular antibiotic cycling for recurrent SIBO, mycophenolate mofetil, prednisone and esomeprazole/itopride slow-release capsules. Patient perspective: "when I first came to Gastro and Liver Centre, I was very down. I was very uncomfortable and could not do simple things. It got so bad I had to stay home and have my family care for me, and although I am very thankful for their help, it was very hard needing others to care for me. I had been independent all my life. Honestly, my quality of life was so poor. But after starting treatment, all my symptoms greatly improved. I am now fully independent again, I am eating well and sleeping well. Everything is good now! My follow-up has been smooth sailing. Well, other than some mild bloating." Informed consent: the patient was informed about the case report, why her case was unique, and how her case would be an invaluable addition to the limited medical information available on her condition. She gave informed consent to have this case report written up and published.

kenya, systemic sclerosis, case report, gastrointestinal system

PMC7083182_01

Male

A 77-year-old man was admitted to the internal medicine department for a 5-day history of progressive preauricular swelling. The swelling was painless, insidious in onset and progressively increased in size. The patient had been previously evaluated by his primary doctor on 2 occasions and was on oral ciprofloxacin without any improvement. The patient reported that he felt weaker than usual over the past 7 days. No history of fever, cough, shortness of breath or weight loss was noted. His past medical history was relevant for end-stage chronic renal disease secondary to diabetic nephropathy, hypertension, coronary artery disease and chronic obstructive pulmonary disease. His family history was relevant for type 2 diabetes mellitus and hypertension. With respect to social history, he had no known drug or food allergies, as well as no history of smoking, alcohol abuse or illicit drug use. There had been no exposure to tuberculosis and no recent travels. The physical examination revealed an alert patient with a regular pulse rate of 84 beats/min, blood pressure of 110/70 mmHg, a respiratory rate of 20 breaths/min and an oxygen saturation of 95% while breathing room air. Local examination revealed a 4x3 cm swelling in the left parotid region that was slightly tender accompanied by small non-painful anterior cervical lymphadenopathies. Heart sounds were regular without any rubs or murmurs. The lungs were clear. The rest of the physical examination was normal. Blood tests showed elevated C-reactive protein (330 mg/l), leucocytosis (17.59x109/l) with a predominance of polynuclear neutrophils (13.72x109/l) and thrombocytosis (555x109/l). The glomerular filtration rate (GFR) was 15 ml/min, serum creatinine was 357 mumol/l and urea was 31.8 mmol/l. Electrolytes were within normal ranges. Coagulation, liver and thyroid tests were normal. Angiotensin-converting enzyme, antinuclear antibodies and anti-SSA/SSB were negative. Serology for HIV, HBV, HCV, CMV and EBV returned negative. Blood cultures were negative. Ciprofloxacin was discontinued and intravenous ceftriaxone 1,000 mg and metronidazole 500 mg 3 times per day was initiated. On day 5 after admission, no clinical or biological improvement was achieved. A non-contrast neck scan was performed; it showed the presence of a significant infiltration of the left parotid compartment with parotitis without any detected collection. The infiltration extended to the left latero-cervical part of the compartment up to the base of the neck with fat infiltration, thickening of the skin and thickening of the superficial cervical fascia (Fig. 1). After discussion, fine needle aspiration cytology (FNAC) was conducted. The cytological assessment showed only neutrophils, lymphocytes and cellular debris. Smear staining with the Ziehl-Neelsen stain as well as a PCR test were positive for Mycobacterium tuberculosis. These results were confirmed with culture of the sample. The patient was diagnosed with tuberculous parotitis and anti-tuberculous drugs were initiated. Chest radiography was normal and the Tuberculosis Skin Test (PPD) was 12 mm.

mycobacterium tuberculosis, parotid tuberculosis, inflammatory swelling

PMC6937823_01

Female

A 57-year-old Chinese woman complained of multiple masses on her body surface for 2 years, mainly in the right cervical and retroauricular lymph nodes, with no tenderness, clear boundary, or mobility. In the absence of treatment, slow progressive enlargement and increase in numbers were noted in the masses, which were palpable on the axilla, chest wall, and groin, as well as unclear demarcation from the surrounding tissues, accompanied by itchiness of the affected skin surfaces. The patient had a medical history of tuberculosis, gastric polyp, and hysteromyoma. Physical examination revealed two subcutaneous masses in the right posterior ear and neck measuring approximately 1 x 1 cm and 2 x 2 cm, respectively, which were solid in texture, with clear boundaries, and fixed to the skin. The skin surface was black, without tenderness, and with a rise in local skin temperature. The enlarged lymph nodes could be palpated on the chest wall and supraclavicular, axillary, and inguinal regions. Obvious scratches were found on the skin of the patient's whole body. Ultrasonography revealed the size of retroperitoneal (maximum 2.2 x 1.2 cm2), bilateral neck (maximum 1.7 x 0.6 cm2 on the left side, 0.8 x 0.6 cm2 on the right side), bilateral supraclavicular (maximum 2.0 x 1.3 cm2 on the left side, 1.3 x 1.0 cm2 on the right side), bilateral axillary (maximum 2.8 x 1.1 cm2 on the left side, 2.9 x 1.8 cm2 on the right side), and bilateral inguinal (maximum 3.0 x 1.3 cm2 on the right side) superficial lymph nodes. Enlargement of multiple lymph nodes was found in all areas (Fig. 1). Many solid nodules with a maximum size of 2.7 x 1.6 cm2 and 1.9 x 0.6 cm2 were found in the right parotid gland and right posterior neck, respectively (Fig. 2). Numerous solid nodules were seen on the left chest wall with a maximum size of 1.5 x 1.0 cm2. Pulmonary computed tomography (CT) scan showed obsolete pulmonary tuberculosis in the upper lobe of both lungs and localized dilatation of right upper lobe and middle lobe bronchi. Abdominal CT showed slightly high density of the left kidney. Laboratory tests showed that the percentage of eosinophils in the patient's whole blood was 39.40% (normal value is 0.4-8%), eosinophil count was 2.68 x 109/L (normal value is 0.02-0.52 x 109/L), and erythrocyte sedimentation rate was 47 mm/h (normal value is 0-20 mm/h). Blood sugar, urea, creatinine, and bilirubin levels and liver and kidney function biomarkers were within normal range. No abnormality was found in the routine urine test. Serum total immunoglobulin E (IgE) level was > 5000 kU/L (normal value: < 100 kU/L), serum specific IgE level to Phadiatop was 1.01 KUA/L (inhalation allergen screening, normal value: < 0.35 KUA/L), and serum specific IgE level to fx5 was 1.04 KUA/L (food combination, normal value: < 0.35 KUA/L), detected with ImmunoCAP (Phadia 250; Thermo Fisher Scientific Inc.). Allergen patch test was negative. Rheumatism, rheumatoid factor, anti-nuclear antibody, complete parasite set, routine stool and urine, thyroid function, immunoglobulin G4, complement C3/C4, and D-dimer levels were normal. After a complete examination, we resected the masses in the right neck, retroauricular and left axillary regions, and left chest wall directly. Postoperative pathological findings showed KD in the right neck, left chest wall, and left axillary lymph nodes (Fig. 3). Immunohistochemistry of the T lymphoid tissue suggested CD2, CD3, CD5, CD7, CD4, and CD8 positivity; BCL-6, CD10, and PD-1 negativity; no identified Reed-Sternberg (RS)-like cells (CD15 and CD30 negative) and proliferation of follicular dendritic cells (FDCs); and a nodular FDC network for CD21 (Fig. 4). The final diagnosis for this patient was KD. Low-dose radiotherapy may have been the best treatment, but she refused and only received glucocorticoid maintenance treatment after surgery; therefore, prednisone 60 mg QD orally was administered to the patient for 2 weeks and the dose was then gradually reduced over another 6 weeks. Lymph node enlargement ceased after 8 weeks of treatment. The patient is still taking prednisone 10 mg once a day, and the symptoms are well controlled even after 1 year.

eosinophils, immunoglobulin e, kimura’s disease, lymphocyte, multiple body

PMC6026928_01

Female

The patient, a 46-year-old female, presented to our department with complaints of continuous urinary incontinence. Her medical history included laparoscopic hysterectomy because of uterine myoma 2 months before her visit. Complete blood count, routine biochemistry parameters, urinalysis, urine culture, and urinary system ultrasonography results were all normal. We identified a 5-mm wide fistula between the bladder trigone and the upper part of the vaginal vault with flexible cystoscopy at the outpatient clinic. The patient was catheterized for 3 weeks. The patient who had catheterization failure underwent transvesicoscopic bipolar sealing of the vesicovaginal fistula (TBSF) after 3 months from her primary gynecologic surgery. The patient signed an informed consent form after she was advised on the use of the novel modified surgical procedure. The operation was conducted with the patient in lithotomy position under spinal anesthesia. A prophylactic antibiotic (second-generation cephalosporin) was given half an hour before the induction. The VVF was identified with a cystoscope using insufflation of gas and it was verified by a guidewire (Fig. 1). The vagina was packed with vaseline-soaked gauze to prevent leakage during bladder filling and escape of CO2 during vesicoscopy. A 5-mm laparoscopic port was placed into the bladder under cystoscopic guidance in the lateral of the midline, halfway between the umbilicus and symphysis pubis. The second 5-mm port was placed into the bladder laterally at the midline and inferior to the first port (Fig. 2). A cystoscope was used as a transurethral camera for vesicoscopy. Bladder mucosa and muscular layer were gripped with a forceps and raised up for a multilayer closure. The fistula tract was grasped and sealed by an EBVS (LigaSure 5 mm blunt tip 37 cm sealer; Medtronic, Inc., Dublin, Ireland) (Fig. 3). An 18F Ryle's tube was kept in the bladder as a cystostomy through one of the existent ports. The bladder was also catheterized. The operative time was 65 minutes. Blood loss was minimal and could not be measured in the case. There were no intraoperative or postoperative complications. The patient was allowed oral intake within 3 hours, to move within 12 hours postoperatively, and was discharged after removal of the cystostomy on the first postoperative day. The Foley catheter was kept in place for 3 weeks. An oral anticholinergic was given until the removal of the Foley catheter. The patient was instructed to return to our office 3 weeks after surgery for urethral Foley catheter removal and subsequent cystoscopic and vaginal inspection to confirm VVF repair (Fig. 4). During a 3-month follow-up, the patient remained continent, and the laboratory results were within normal range.

bipolar, sealing, vesicoscopic, vesicovaginal fistula

PMC10417010_01

Male

The burnt body of a 53-year-old man was found at the fire scene. All layers of the skin are observed to be damaged in the areas of the body not covered by clothes, charred soft tissues and muscles without a pronounced tissue reaction. Histological examination revealed no inflammatory reaction of tissue. I -IV postmortem burns cover about 45% of total body surface area (TBSA). A compression fracture of the left temporal bone was found with hemorrhage of the surrounding soft tissues, infiltrating hemorrhages in the dura mater, isolated hemorrhages in the left temporal lobe (Fig. 1).

antemortem burning, burned bodies, forensic science, homicide, postmortem burning

PMC10417010_04

Female

A burnt body of a 40-year-old woman was found in the forest. The body is completely split (burnt) in the middle part of the body (Fig. 5). The upper part of the body ends at the 10th thoracic vertebra and the remaining lower part of body begins in the front just above the navel, on the left at the level of the lower quadrant of the buttock, on the right at the right hip joint. Burns cover about 90% of TBSA, complete burning of the soft tissues of the torso, hands, and bones. These burns are postmortem, as indicated by the lack of reaction of the surrounding tissues during the examination of the body and the data of the histological examination. Histological examination revealed no inflammatory reaction of tissue. Moreover, bruises were found in the soft tissues of the tongue, face, and both temporal areas without any cellular reaction. Observed injuries were caused by contact with hard blunt objects and it is probable that they could have been caused by blows to the above-mentioned areas of the face. Nonetheless, these hemorrhages are nonfatal injuries. On the back surface of the left thigh, light purple lividity can be distinguished, which does not change color when pressed with a finger.

antemortem burning, burned bodies, forensic science, homicide, postmortem burning

PMC9592198_01

Female

XX is a medical resident aged between 30 and 40 years old. She presented a cyclothymic temperament with traits belonging to borderline personality disorder. When she was a child, she experienced a traumatic event of loss as she witnessed the sudden death of a parent. XX then developed feelings of emptiness; fear of abandonment from other attachment figures; emotional swings with quick change to sadness, anger, and anxiety; or impulsive behaviours that led to a first suicide attempt by drug ingestion at the age of 14. In the following years, the subject continued to experience mood swings. These were mainly depressive in nature with a subsequent compromission of her interpersonal skills though not of her intellectual performance. The patient maintained a very strong academic performance in school. In her last year of medicine, around the age of 25, under pressure for exams and the required final thesis, the subject developed a depressive episode according to DSM-5, characterized by low mood, loss of enjoyment in most activities, anxiety, hypoergy, difficulty with concentration, and insomnia which led to a great increase in alcohol use together with benzodiazepines. She turned to a psychiatrist and started various antidepressants (including citalopram, venlafaxine, and duloxetine). However, the clinical benefits of these antidepressants were poor, and she continued to have mood swings alternating between moments of sadness and pervasive anxiety and moments of increased work performance, self-confidence, increased involvement in hobbies as writing poetry and reading, more energy, and decreased need for sleep. Alcohol abuse remained stable through the alternation between the various mental states. Two years later, during her first year of residency program, she presented a worsening of the psychopathology framework developing a mood episode with mixed features according to DSM-5. During that period, she started a binge use of anesthetics (midazolam, propofol), and she reached a total deterioration of general personal functioning. This was followed by hospitalization for about two weeks and discharge with a diagnosis of Bipolar Disorder (BD) and Alcohol Use Disorder (AUD) and a pharmacological treatment with valproic acid (immediately suspended by the patient herself), anxiolytic stabilizers (gabapentin), atypical antipsychotics (quetiapine), and benzodiazepines (lorazepam), again however with poor clinical benefit. During the next two years, she continued to experience mixed-depressive symptoms, despite the therapeutic attempts, which led to several hospitalizations and, at the age of 28, to another suicide attempt by means of lithium salt ingestion with intoxication that led to temporary cardiac arrest. In the following years, she continued to show mood instability that she managed by herself, combined with a daily use of alcohol that allowed her to recover her ability to work and thus return to her residency program. Nevertheless, she presented a poor adaptation on the social and leisure plan with no social circle and a lack of confidence in social situations. In 2018, following a new worsening of the psychopathological elements with a daily alcoholic consumption of about two to three beers a day, she attempted suicide again by means of a massive ingestion of her psychiatric treatment. She was again hospitalized and started a new therapeutic program based on buprenorphine (now at 8 mg/day), various mood stabilizers then discontinued, benzodiazepines: clonazepam (later discontinued) and currently delorazepam (now 4 mg/day), tricyclic antidepressants (amitriptyline 75 mg/day), and antidepressant SARI (trazodone, 75 mg/day). Since then, the patient has shown a slight improvement in her mood and was admitted for some weeks to a therapeutic community for alcoholics from which she reported that she emerged detoxified. In 2019, she continued her residency with relative stability and good performance. In March 2020, with the outbreak of the COVID-19 pandemic, she was assigned to a COVID-19 emergency unit. At that point, due to various risk factors and vulnerabilities for an alcohol abuse and psychiatric relapse, the patient asked for support to deal with new stressful situations present in the workplace. As a result, the subject's case was assigned to the multidisciplinary group of the Occupational Medicine Unit (see Figure 1). Blood count tests showed no signs of recent alcohol abuse though the subject's liver was slightly compromised. The subject denied any kind of alcohol and recent drug use except for smoking. She reported feelings of anxiety and frustration because of exclusion from procedures of her level of expertise due to her psychiatric history. Evaluation revealed that the subject suffered from a very low mood with general flattening, detachment, and difficulty concentrating. The patient did however deny suicidal ideation. At the time of the evaluation, she presented a working function within acceptable limits but still had difficulty in organizing daily life and suffered from poor social relations. She had no friends at work or outside and no emotional relationships. Our group confirmed the diagnosis of BD (according to DSM-5) with previous AUD and some features of borderline personality. XX was offered a personal plan of monitoring of alcoholemia and periodic blood tests together with psychiatric evaluations and the possibility of new pharmacological treatment. The occupational psychiatrist (with a specialty both in psychiatry and psychotherapy) managed psychological and psychiatric interventions. XX presented borderline personality traits with bipolar depression symptoms and posttraumatic stress elements due to the nature of the work environment brought about by the COVID-19 pandemic. She presented a flattened life likely due to prolonged use of alcohol and benzodiazepines. Consistent with the complex clinical elements of XX, previous addictive behaviours, suicidal ideation, drug resistance, and her professional role, the need to prescribe and manage off-label medications was evident. In accordance with these considerations, in agreement with XX and with the occupational physician, the occupational psychiatrist requested a consultation with the service provided for persons with pathological addictions (Servizi Dipendenze: SerD) and an addictology psychiatrist. The final maintaining treatment was the following: buprenorphine, lithium, methylphenidate, and delorazepam together with weekly sessions of third generation of Cognitive Behavioural Therapy (CBT) with integration of Mindfulness and Acceptance and Commitment Therapy (see Table 1). The occupational team, with the consent of XX, informed her supervisor about the surveillance program and the psychiatric treatment choice and, with his assistance, drew up a new flexible working plan, more appropriate to XX's level of experience but with assistance and monitoring of her hazards. During the following year, XX followed the Occupational Unit's indicated treatments and was able to maintain her stability and finish her residency program.

PMC5505615_01

Male

An 82-year-old man presented with blood-tinged sputum, dizziness, and a 3 kg weight loss over 6 months. He had been taking medications for hypertension and diabetes, and had had pulmonary tuberculosis 40 years earlier. He quit smoking 13 years earlier, but had a smoking history of 60 pack-years. Written informed consent has been provided by the patient to have the case details and any accompanying images published. Chest computed tomography (CT) revealed multiple fluid-containing bullae and a contrast-enhancing 2.5 cm mass with a lobulated margin in the right lower lobe of the emphysematous lung (Figure 1A). Histologically, tissue from a percutaneous thoracic needle biopsy of this mass showed that it consisted predominantly of spindle-shaped cells with moderate pleomorphism, hemorrhage, and necrosis. The mitotic rate was four figures in 10 high-power fields. Immunohistochemical staining was positive for desmin and smooth muscle actin, and negative for ALK, Pan-CK, CAM5.2, HMB45, Melan-A, P40, and TTF-1. The pathology and immunohistochemistry findings were consistent with leiomyosarcoma. Whole-body 18F-fluorodeoxyglucose positron emission tomography-CT did not detect any pathologically increased uptake, except above the mass, with a maximum standardized uptake value of 2.24. No specific findings were seen on brain magnetic resonance imaging. The patient was deemed inoperable medically because of his poor medical condition and old age. The small tumor size and its location at the lung periphery permitted the application of SABR, instead of conventional RT. During the simulation, the patient was immobilized in the supine position with his arms above his head. Respiration-correlated four-dimensional CT was conducted using a Real-Time Position Management system (Varian Medical Systems; Palo Alto, CA, USA) and a 16-slice CT scanner (Brilliance CT Big Bore, Philips Medical Systems, Cleveland, OH, USA). Each of 10 CT images reflected 10% of the respiratory cycle. The clinical target volume was delineated on the CT images for each respiratory phase using the lung window setting. The planning target volume was created by adding a 0.5 cm isotropic setup margin around the internal target volume, which was the sum of the clinical target volumes during all 10 respiratory phases. A volumetric modulated arc therapy plan was created using the Eclipse treatment-planning system (Varian Medical Systems) and 6 MV photons, with inhomogeneity corrections (Figures 1B and C). The dose fractionation scheme was 56 Gy in four fractions delivered every other day in February 2015. SABR was performed on a Novalis Tx system (Varian Medical Systems and Brainlab, Feldkirchen, Germany). A complete tumor response to SABR was observed on chest CT 2 months after the SABR (Figure 1D). Diffuse consolidation with ground glass opacity in the right lower lobe indicated the development of radiation pneumonitis. He developed a productive cough for about 1 month, but this subsided with conservative management. Follow-up chest CT was repeated every 3 or 4 months, and he is alive with no evidence of disease for 2 years.

leiomyosarcoma, primary lung sarcoma, radiation therapy, sarcoma, stereotactic ablative radiotherapy, stereotactic body radiotherapy

PMC8180893_01

Male

A, a 25-year-old man with alcohol use disorder, presented with a chief complaint of feeling "lonely and frustrated." His father was his sober support person. Birth was reported difficult with more than 12 h of labor and use of opioids for analgesia. Past psychiatric history was significant for ADHD, and "anxiety, and depression," his pediatrician had diagnosed when he was 16. He described family as "disconnected" since his parents' divorce. He felt "trapped" while living with his mother. Therefore he relocated and has lived with his father, "Since some time just after [high school] graduation." He described distant sibling relationships "because they all hate my dad for some reason. Because I'm the only one giving him a chance they don't talk to me." A described a long history of poor communication and difficulty socializing. Throughout his education he was in "special classes" that he feels were stigmatizing and responsible for "making it really difficult to have friends at school. Everyone looked at us like we were weird and didn't want to be seen with us." After high school, A worked as a custodian for a few months at a college until, for unclear reasons, he was terminated and barred from the campus. A stated, "I just decided that being alone all the time, at work and at home, wasn't good for me and never went back." This was his only significant work in the seven years since high school graduation. He spent much of his time indulging in alcohol, tobacco, and cannabis and avoiding social interactions. Alcohol consumption had been responsible for a hospital admission for withdrawal, an inpatient rehab followed by six months in a half-way house, and a drinking dream, suggestive of alcohol changing his ventral tegmental dopaminergic SEEKING system to produce alcohol craving (Johnson,). During the initial interview he described feeling nauseous and agitated as we discussed his relationship with addicting substances. His mental exam was remarkable for tense posture, marked fidgeting, and gaze avoidance. His thought process was illogical regarding emotions and relationships. Affect was remarkable for dysphoria and irritability. His mood was described as "confused." Insight and judgment were poor. Hamilton Rating Scale for Depression was 21, severe. A's SCID-2 screen for Borderline Personality was positive with 8/15 items checked. DSM5 criteria were ADHD positive for six inattentive and four hyperactive symptoms. Expired carbon monoxide was 8 part per million reflecting current cigarette use. Cognitive function was perfect. Diagnoses were Major Depressive Disorder, ADHD, Inattentive Type, Tobacco, Cannabis, and Alcohol Use Disorder. We gave A and his father rating scales. The SRS-2 is validated for adults (Chan et al.,). The patient self-rates with a score above 75 indicating severe autism. The SCQ is observer rated; a score of 23.08 is the standardized mean for a diagnosis of autism (Rutter et al.,). A scored 79 on the SRS-2. The father rated 27 on the SCQ with a threshold for diagnosis of ASD being 15. On day 8 cold pressor time (CPT), an ice water bath measuring pain tolerance by timing duration of forearm submersion, was 190 s. Our control average using support persons is 113 s. The withdrawal at 190 s seemed more from annoyance at feeling confined and controlled by remaining stationary rather than intolerable pain. A trial of naltrexone at 25 mg (0.39 mg/kg) was discussed. A was reluctant to begin naltrexone but provided no reason for his objection. On day 21, A reported improvement in ADHD and depression with twice a week transference focused psychotherapy and bupropion 450 mg/day. After showing these signs of clinical improvement a trial of naltrexone was revisited. A was apprehensive. He demonstrated an odd rationale about how naltrexone might injure him. We find autistic patients express pride at being autistic, as A did. They speak as if among many frustrations of their life they possess one outstanding quality:being autistic. We clarified his concerns and interpreted rationalizations regarding avoiding treatment. A agreed to begin naltrexone. On day 28 A started 25 mg naltrexone with improvement in relatedness and odd thinking by day 35. We felt the therapeutic effects of naltrexone 25 mg had plateaued. We increased the dose to 50 mg. A felt significantly better with improved relatedness and clearer thinking. His CPT was 28 s on 50 mg of naltrexone with a repeat CPT of 39 s a week later. CPT falling from 190 s to 28 or 39 s is thought to represent decreased central nervous system opioid tone, moving A toward the top of the inverse parabolic function in Figure 1. Closeness caused pleasure rather than pain. But A could also feel the pain of emotional responses to relationship problems. On day 55, A lost his naltrexone prescription. We did not hear about this until inquiring about worsening gaze avoidance, confused thinking, and deterioration of relatedness. At his psychotherapy hour he smelled foul as if self-care had deteriorated. One evening soon after he cut his left palm with a knife so deeply that the wound required 11 sutures. It was as if A had decided, "I needed to feel pain." This may have been an attempt to upregulate pain drivers to balance high opioid tone. Again there was reluctance to take medication as his odd thinking prevented appreciation of naltrexone's benefits. His father came to his psychotherapy hour and it was agreed A would restart naltrexone. On day 65, A returned with vast improvement in mental status on 50 mg of naltrexone. On day 74, A decided to increase naltrexone to 75 mg (1.17 mg/kg). Initially, he felt better. However, after a few days, with no discussion in psychotherapy, he returned to 50 mg. A stated, "At 75 mg I didn't feel like I was on anything." This is consistent with 75 mg pushing A out of the 2-4 range of Figure 1, and into the 0-1 range of opioid tone where pain is identical to the 5-6 autistic range of opioid tone. Overall, A felt marked improvement at naltrexone 50 mg. He said, "I can watch a basketball game now with my father without losing interest or wanting drugs or alcohol." He stopped alcohol, tobacco, and cannabis. Although we attributed the cessation of drug use to his psychotherapy, it may be that naltrexone also made a contribution. Naltrexone is an approved drug for Alcohol Use Disorder. On day 85, A's father rated him a 9 on the SCQ:not consistent with autism. A rated himself 54 on the SRS-2, considered normal. On day 98, A was hired for a job loading trucks, full time at $14 per hour, and had purchased a new car. He reported positive interactions with coworkers. Soon after he terminated psychotherapy. On day 166, A had again stopped his naltrexone. He got drunk, crashed his car, and lost his driver's license for a year. A has re-engaged in psychotherapy. Its focus has become negotiating painful relationships including the relational difficulties he encounters with his therapist. Two years into his psychotherapy A has been working full-time since day 98. He talks mostly about his work relationships. Like other patients with major mental illness, sharing drugs becomes a way of engaging with others. He has resumed inhaling tobacco. He described with great pleasure asking a supervisor for a cigarette. "We walked the whole length of the warehouse to his office. He said, 'I wouldn't do this for any deadbeat but you work hard so I'll happily give you one of mine.'" Coworkers who inhale tobacco with him on breaks are characterized as, "Good, social people with a lot going on." Figures of external authority, such as law enforcement and physicians who, "Always have such a serious look on their face," are associated with projected judgment and feeling inadequate, evoking guilt and shame. "Court is the worst because everyone is serious. Everyone looks at you like there's something wrong with you." A's reflective accounts of school are often externalizations he experiences as pondering other people's thoughts of him. He questions whether people past and present were/are honest about their perceptions. This identity question is part of A's transference and a focus of his continuing psychotherapy. The paranoid thinking about external judgments and malevolence has consistently been examined in the transference, "Are we judging you?" By two years into treatment the paranoia is gone. A is working on developing relationships that he now desires.

autism, case report, cold pressor test, neurobiological systems engineering, opioid tone

PMC5941976_04

Male

A 57-year-old man with a past medical history of pulmonary tuberculosis and severe COPD was admitted for a spontaneous pneumothorax. Chest CT demonstrated significant RUL bullous disease. The patient underwent video-assisted thoracoscopic surgery, with resection of apical and posterior segments of the RUL. It was felt that the anterior segment was less diseased, and given the severity of baseline compromise and the need for tissue sparing, it was decided that the anterior segment was better not resected. A postoperative leak was present, and on postoperative day 5, IP was consulted; a completion lobectomy was not considered, again due to severity of underlying disease. Bronchoscopy with balloon occlusion was performed in the ICU. Sequential balloon occlusions from the proximal to the distal airways failed to impact the rate of air bubbling through the fluid chamber of the water seal chest drain. Whereas the BPF most likely emanated from the area of resection, the RUL, EBVs were empirically placed in two adjacent segments, the remaining anterior segment of the RUL and the superior segment of the right lower lobe (RLL), with a marked decrease in air leak. The next day, however, there was a marked increase in leak. Bronchoscopy with balloon occlusion was again performed, this time under general anesthesia in the OR. Only minimal reduction of the leak was seen, even with occlusion of the right main bronchus. The chest tube was clamped at its exit from the chest wall, with complete cessation of bubbles in the water chamber. This maneuver demonstrated that there was no defect in the chest tube apparatus external to the thorax. Given the lack of benefit from the previously placed EBVs, they were removed. A CT of the chest was ordered to look for an anatomic explanation for the EBV failure. This showed that the chest tube had migrated into an apical bleb present in the unresected anterior segment of the RUL. Based on these findings, the chest tube was clamped despite the air leak. The postclamp chest X-ray was stable without any evidence of a pneumothorax, and the chest tube was removed 2 days later, with repeat chest roentgenogram showing no pneumothorax. The patient was subsequently discharged in stable condition.

bronchopleural fistula, endobronchial valves, prolonged air leak

PMC7302885_01

Female

A 44-year-old woman presented to the emergency room at our institution with chest pain and shortness of breath. She had no significant past medical history or family history. She denied any history of smoking, alcohol consumption or illicit drug use. A year prior to this visit, she had presented to another hospital with similar complaints. The workup at that time demonstrated pericardial effusion, and the cytology of the pericardial fluid was suggestive of exudative effusion. At that visit, she was diagnosed with latent tuberculosis after a positive tuberculin skin test and received treatment with isoniazid for 6 months. However, her symptoms kept worsening over 6 months, and she presented to our hospital with severe shortness of breath. She gave a history of dyspnea on exertion, occasional squeezing non-radiating chest pain and palpitations. The review of systems was notable for anorexia and significant weight loss over the last six months. At the time of the presentation, she was in significant respiratory distress. The systemic exam was significant for jugular venous distention, bilateral pitting edema of lower extremities, pallor, and use of accessory muscles of respiration. The cardiovascular exam was significant for soft first heart sound and non-palpable apex. The rest of the systemic examination was unremarkable. Labs at presentation were remarkable for normochromic normocytic anaemia (Hb-11.4 gm/dL) only. The comprehensive metabolic panel, troponin-I and B-natriuretic peptide were normal at presentation. The bedside echocardiogram revealed an ejection fraction of 55%-60%, normal valvular structures, and a moderate, free-flowing, concentric pericardial effusion without tamponade physiology. CT scan of the chest revealed pericardial effusion with a possible pericardial sac mass and multiple bilateral hemorrhagic pulmonary nodules. Cardiac CT showed a highly vascular, right atrial wall soft tissue mass involving the adjacent pericardium associated with large pericardial effusion (Figure 1). CT guided biopsy of the mass showed a tumour with spindle and epithelioid cells, prominent nucleoli and irregular vascular channels (Figure 2). CD31 and CD34 stains were positive in the tumour cells and highlighted the vasculature. The tumour cells were negative for keratin AE1/AE3, EMA, BerEP4, CK7, TTF-1, calretinin, CK5/6, MART-1, HMB45 and S-100. The patient had metastatic disease at the time of diagnosis. She was treated with AIM 75/10,000 regimen (doxorubicin 25 mg/m2 on day 1-3, ifosfamide 2,000 mg/m2 on day 1-5 with mesna and granulocyte colony-stimulating factor support). She completed six cycles of treatment with 25% dose reduction and minor treatment delays due to two episodes neutropenic fever. A partial response was noted after six cycles with at least 50% reduction in the tumour burden. However, within 6 weeks of completing treatment, she was diagnosed with progressive disease and opted for hospice.

angiosarcoma, cardiac tumour

PMC5012837_01

Male

A 34-year-old African man was referred to our hospital because of microscopic hematuria identified at an annual health checkup at his workplace. The patient had no significant past medical history and was not taking any medications. The patient gave written informed consent to be included in this case report. Upon initial routine workup, the patient's HIV test was positive. Subsequent blood tests showed CD4 count was 139 cells/muL and viral load was 5.1x104/mm3. The patient's serum creatinine level was 0.86 mg/dL, with blood urea nitrogen of 10.1 mg/dL. Urinalysis showed red blood cell (RBC) 3+ and urinary sediment showed dysmorphic RBCs (>100/high power field) with RBC casts and absence of white blood cells. Urine beta2-microglobulin was 913 mug/L, urine N-acetyl-beta-d-glucosaminidase was 14.9 U/L, and urine protein was 0.217 g/d. The patient was subsequently diagnosed with pulmonary tuberculosis and was treated with a standard regimen including four drugs for 2 months, followed by isoniazid and rifampin for 4 months. Because of persistent hematuria, the patient was hospitalized to undergo renal biopsy. The histopathological analysis revealed focal interstitial infiltration of lymphocytes and plasma cells in the renal cortex as well as in the corticomedullary junction, accompanied by mild tubulitis without microcysts (Figure 1). No tubular necrosis was observed, with erythrocytic casts and flattened tubular epithelium (Figure 2). Analysis of glomeruli showed no evidence of podocyte hypertrophy, glomerular collapse, or endocapillary hypercellularity (Figure 2). These findings were consistent with the diagnosis of focal and mild tubulointerstitial nephritis. Ziehl-Neelsen staining of the biopsied specimens was negative, and there were no pathological findings suggestive of tuberculosis. Two weeks after the initiation of treatment for tuberculosis, antiretroviral therapy (ART), including lamivudine, abacavir, and dolutegravir, was started. The 6-month treatment for tuberculosis was completed successfully. Eight months after the initiation of ART, urinary levels of beta2-microglobulin and N-acetyl-beta-d-glucosaminidase normalized and microscopic hematuria resolved completely.

hiv-associated nephropathy, human immunodeficiency virus, interstitial nephritis

PMC6639657_01

Female

A 54-year old Latin American female, with history of type 2 diabetes mellitus and end-stage renal disease presented to the emergency department with a 10-day history of headache and photophobia. She complained of chronic cough, weight loss, and low-grade fever. She reported close contact with a person with pulmonary tuberculosis three years prior to her admission. On physical examination, she was febrile (38.5 C), tachycardic and had mild impairment of alertness. Pulmonary auscultation revealed diffuse crackles mainly of the left lung. Initial laboratory studies showed white blood cell count (WBC) 4800 cells/muL; absolute lymphocyte count 816 cells/muL; hemoglobin 10.3 g/dL; and blood sugar 111 mg/dL. Liver function tests were normal, creatinine 7.2 mg/dL; and blood urea nitrogen 59 mg/dL. The chest x-ray showed bilateral interstitial infiltrates and brain magnetic-resonance images showed multiple ring-shaped lesions in posterior areas of both hemispheres. Acid-fast bacilli sputum culture was positive on Ziehl-Neelsen stain and grew Mycobacterium tuberculosis complex (MTB) with no evidence of antibacterial resistance. HIV1/2 and toxoplasma serologies were negative. On lumbar puncture, the opening pressure was 30 cm H2O. Analysis of the cerebrospinal fluid (CSF) showed red blood cell count 1000 cells/muL; WBC 114 cells/muL; lymphocytes 92%; glucose 30 mg/dL; and proteins 161 mg/dL. CSF neurocysticercosis serology and cryptococcal antigen were negative. CSF Mycobacterium tuberculosis stain and culture and adenosine deaminase were negative, whereas a polymerase chain reaction (PCR) was positive for MTB. Anti-TB therapy was started with rifampin, isoniazid, pyrazinamide, ethambutol and pyridoxine with adjunctive dexamethasone planned for 8 weeks. A few days later, her mental status rapidly deteriorated requiring admission to the intensive care unit and initiation of hemodialysis for uremia, which resulted in clinical improvement. After three weeks of hospitalization, she developed acute abdominal pain and hematemesis. A computerized tomography (CT) of the abdomen revealed a loculated multiseptated gas and fluid collection along the posterior aspect of the gastric fundus with free intra-abdominal air consistent with gastric perforation (Fig. 1a). An exploratory laparotomy demonstrated complete stomach necrosis (Fig. 1b). She underwent a total gastrectomy with intestinal discontinuity followed by cervical esophagostomy and jejunostomy tube (J-tube) placement. Oral anti-TB therapy was switched to intravenous treatment with amikacin, linezolid, levofloxacin and rifampin. The patient developed septic shock, requiring intubation and mechanical ventilation. Empiric broad-spectrum antibacterial therapy was initiated with piperacillin-tazobactam for intra-abdominal infection. Histopathology of gastric tissue on hematoxylin and eosin (Fig. 1c) and Grocott-Gomori methenamine silver stains showed broad, irregularly branched, rarely septate hyphae consistent with angio-invasive gastric mucormycosis. The acid-fast bacilli stain and culture were negative. Liposomal amphotericin B 7.5 mg/kg daily was initiated and TB treatment with levofloxacin, rifampin, isoniazid, and linezolid was maintained for one more month. Then, isoniazid plus rifampin were continued by jejunostomy tube to complete 12 months of treatment. Liposomal amphotericin B was switched to posaconazole as oral suspension 200 mg/6 h per J-tube. Upon clinical stabilization and improvement, she returned to her country of origin in Latin America to finalize her treatment.

diabetes mellitus, mucormycosis, tuberculosis

PMC10220441_01

Female

A 16-year-old girl presented with pain, redness, watering, and blurred vision in her right eye for 4 days. There was no history of ocular trauma, surgery, or contact lens use. She had a history of fever 15 days before this episode associated with burning micturition, papulomacular rash over the lower abdomen and groin, and vague joint pains for which she took symptomatic treatment elsewhere (no previous records available). Currently, the patient was using topical antifungals and antibiotics in the right eye for the past 2 days. On examination, her best-corrected visual acuity (BCVA) was hand movements close to the face in the right eye and 20/20 in the left eye. A slit-lamp examination of the right eye showed intense circumcorneal congestion and a ring-shaped corneal infiltrate with an epithelial defect measuring around 6 mm x 6 mm. The anterior chamber was quiet with no hypopyon and the lens was phakic [Figure 1a]. Fundus examination revealed hazy media due to corneal involvement with a disc hazily seen and a retina attached. The left eye appeared normal. Corneal sensations were intact in both eyes. Corneal scrapings were obtained and sent for microbiological analysis. Gram stain of corneal scrapings revealed Gram-negative rods and culture yielded heavy growth of K. pneumoniae [Figure 2] later identified as ESBL producers by VITEK (automated method for antibiotic sensitivity testing). Antibiotic susceptibility testing determined by agar disk diffusion (Kirby-Bauer method) showed that the isolates were sensitive to amikacin, gentamicin, tobramycin, tigecycline, and trimethoprim-sulfamethoxazole. The patient was started on fortified amikacin (2.5%) and fortified tobramycin (1.3%) hourly with cycloplegic drops in the right eye. In view of the recent history of fever with rash and joint pains, pediatric consultation was sought to rule out a systemic cause for corneal ulcer which could be autoimmune or infective. Her blood investigations included a complete blood count with an erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), random blood sugar along with blood culture, Mantoux test, and chest X-ray. HLA B27, rheumatoid factor, and antinuclear antibody were done to rule out any autoimmune cause. Ultrasound abdomen and pelvis were done to look for any septic foci which came out to be normal. Investigations revealed leukocytosis, raised ESR (102 mm), CRP (26.1 mg/dL), and blood culture with confluent growth of K. pneumonia after 24 h of incubation. Rest investigations were negative. Hence, a probability of endogenous Klebsiella keratitis in the right eye was considered, although the exact source of the primary infection could not be detected. The patient was admitted and started on intravenous antibiotics gentamicin and piperacillin with tazobactam based on the blood culture sensitivity report. After 1 week of treatment, the patient's systemic symptoms resolved. Ocular examination showed a resolving corneal infiltrate with no epithelial defect and BCVA improved to 20/200 in the right eye [Figure 1b]. The patient was discharged and was kept on follow-up. One week later, she reported to us with redness and watering in her left eye. On examination, her BCVA was 20/40 in both eyes. Slit-lamp examination showed a scarring ring infiltrate in the right eye with mild corneal edema [Figure 1c]. There was a paracentral stromal infiltrate measuring 2 mm x 2 mm with no epithelial defect, quiet AC, and no hypopyon in the left eye [Figure 1g]. Corneal scraping was deferred in view of the small infiltrate size (<=2 mm) and no epithelial defect. The patient was started on the same fortified antibiotics considering the likelihood of Klebsiella keratitis in this eye as well. One week later, the patient came for a follow-up which revealed scarred infiltrate in the right eye [Figure 1d] and diffuse stromal edema, granulomatous keratic precipitates (KPs), and 3+ cells in AC in the left eye [Figure 1h]. The patient was investigated thoroughly to rule out uveitis due to any other pathology (tuberculosis, sarcoidosis, and syphilis) which came out to be negative. She was started on topical steroids six times a day along with antibiotics and cycloplegic drops keeping a possibility of immune-mediated pathology in the left eye. A diagnosis of healed endogenous Klebsiella keratitis in the right eye with immune-mediated keratouveitis in the left eye was made. On the 2-week follow-up, her BCVA improved to 20/20 in both eyes with scarred infiltrate and quiet AC bilaterally [Figure 1d and i]. Her fundus examination was normal on all the visits [Figure 3]. The patient was doing well when 4 months later; she again had a similar episode of uveitis in the right eye [Figure 1e]. This was preceded by a fever for 1 day which resolved on symptomatic treatment. There were no other systemic features. Blood investigations were negative. Hence, a possibility of recurrent uveitis secondary to endogenous infection was kept and was successfully treated with a short course of topical steroids [Figure 1f]. The patient is on follow-up for the past 6 months and maintains a BCVA of 20/20 OU with normal intraocular pressure and quiet AC.

amikacin, klebsiella keratitis, endogenous infection, extended-spectrum beta-lactamase-producing, ring infiltrate, tobramycin

PMC4555908_01

Female

A 60-year-old married female patient presented to us with asymptomatic gradually increasing skin lesion on vulva since 2 years. There was no history of risk of exposure to sexually transmitted diseases. There was no history of discharge from the lesion. No history of white discharge per vaginum or burning micturition. She had not taken any treatment in the past for the same. No past history of tuberculosis. Examination revealed a firm, nontender, nodular plaque of 3.5 cm x 2.5 cm along with a few shiny papules along the right labia majora [Figure 1a]. The left labia majora, labia mijora, clitoris, and perianal areas were not involved. Oral mucosa was normal. There was no regional lymphadenopathy. Differential diagnoses considered were fibrosis lymphangioma circumscriptum, giant trichoepithelioma, sarcoidosis, lupus vulgaris, and deep fungal infection. Histopathology from the lesion showed numerous horn cysts present throughout the dermis surrounded by eosinophilic cells [Figure 2a]. Few of the cyst walls were lined by eosinophilic epidermal cells and contained keratin [Figure 2b]; thereby leading to a diagnosis of a less known adnexal tumor trichoadenoma.

co2 laser, trichoadenoma, vulva

PMC10349569_01

Female

A 40-year-old female was diagnosed with viral encephalitis-induced secondary brain death on September 11, 2019, based on the American Academy of Neurology (AAN) criteria for the determination of brain death in adults. Her clinical manifestations presented as comatose, lack of brainstem reflexes, and cannot breathe spontaneously. The head CT showed diffuse edema of brain tissue and gray matter with white matter structure blurred (Figure 1A). The electroencephalogram (EEG) indicated resting-state brain electrical activity. Her family finally decided to transfer to the Hang Zhou Integrative Medicine Hospital. She received mechanical ventilation and rehabilitation exercise during hospitalization lasting for almost 3 years. The patient had a high fever on September 12, 2022. Physical examination revealed intense swelling of her right occipital region and the abscess was approximately four centimeters in diameter. The brain computed tomography (CT) imaging showed the right temporoparietal cerebral hemorrhage and occipital defect with a subcutaneous abscess in Figure 1B, and laboratory workup showed white blood cell, 9.0x109/L; neutrophils, 87.8%; lymphocytes, 9.1%; red blood cell, 2.84x1012/L; hemoglobin, 86 g/L; platelet, 183x109/L; C-reactive protein, 100.2 mg/L; procalcitonin, <0.25 ug/L. The sampling of abscess fluid was conducted, and bloody pus was obtained (Figure 2). The pus's direct smear examination and culture showed B. cepacia. The colony was susceptible to cefoperazone-sulbactam, meropenem, ceftazidime, minocycline, and TMP-SMX (Table 1). To confirm the result, we further conducted metagenomic next-generation sequencing (NGS) of the abscess aspiration and revealed B. cepacia (Table 2). We analyzed its virulence genes and the major virulence factors focusing on the function of motility, such as fliM, flhA, motA, fliA, flgG, and flgI. We further found that the drug-resistant genes of this strain were mphL, satA_Ba, BcII, and bla1 via the second-generation sequencing of the whole genome. The cerebrospinal fluid examination (CSF) was performed to rule out intracranial infection, and no positive results were seen in the CSF, including CSF routine, culture, Cryptococcus neoformans, Mycobacterium tuberculosis and NGS. She was then treated with Cefoperazone-sulbactam 2.0g q8h for 5 days depending on the result of the antimicrobial susceptibility testing for B. cepacia. By this series of treatments, she had no fever, and the inflammation presented white blood cells, 5.5x109/L; neutrophils, 79.6%; lymphocytes, 17.4%; red blood cells, 3.0x1012/L; hemoglobin, 89 g/L; platelet, 135x109/L; C-reactive protein, 40 mg/L; procalcitonin, <0.25 ug/L. The inflammatory markers were significantly lower than before with no apparent swollen sign of the right occipital area in several days. Worth mentioning is that the patient neither reviewed for the CT nor got enough treatment courses to objectively evaluate the therapeutic effect of the soft tissue abscess with a bone fracture because family members decided to abandon treatments.

burkholderia cepacia, brain death, case report, generation sequencing, subcutaneous abscess

PMC7452135_02

Unknown

In the largest sarcoidosis and breast cancer case series published, to our knowledge, to date, sarcoidosis mainly occurs shortly after breast cancer diagnosis and treatment, with the classical disease features of chest involvement, but at a significantly older age, as compared to our sarcoidosis sine breast cancer patients. Our study does not allow conclusions on a possible association between two diseases, whereas large epidemiological registry-based studies yield contradictory results on the association of sarcoidosis with malignancies. Another limitation of our study is the lack of data on chemotherapy regimens administered in these patients. Last, our data are over 10 years old. In the advent of EBUS-TBNA and recently published studies on two diseases association, we believe our data may be of use for the clinicians involved in the diagnosis and management of sarcoidosis and breast cancer.

breast cancer, interstitial lung diseases, sarcoidosis

PMC6476028_01

Female

A 57-year-old female with a history of hypothyroidism, hyperlipidemia, and glaucoma presented to the interventional pulmonology (IP) clinic for evaluation of lung nodules found incidentally on chest imaging for evaluation of chronic cough. Her dry cough had persisted for 4 months, and computed-tomography (CT) of the chest demonstrated right lower lobe clusters of noncalcified, solid nodules, largest measuring 10 x 15 mm, with an enlarged subcarinal lymph node (LN) measuring 1.4 x 2.8 cm (Figure 1). She denied fever, chills, anorexia, night sweats, or weight loss. She was a never smoker and had no identifiable environmental or occupational exposures. Her physical examination and initial blood work including complete blood count (CBC) and chemistry were unremarkable. The decision was made to pursue biopsy of the enlarged subcarinal LN to test for old granulomatous disease, in particular, histoplasmosis. Under conscious sedation, endobronchial ultrasound (BF-UC180F bronchoscope) was advanced orally and transbronchial needle biopsy (EBUS-TBNA) of station 7 was performed. A total of 4 biopsies were obtained using a 21G needle (ViziShot Olympus). Rapid on-site evaluation (ROSE) commented on excessive necrosis from each pass. Cultures including bacterial, fungal, and acid-fast bacteria (AFB) were negative. Final cytology was negative for infectious and malignant etiologies. Ten days later, she presented to the Emergency Room with complaints of a low-grade fever, shortness of breath, and sharp and posterior right-sided chest pain which worsened since the procedure. Her vital signs and physical examination were unremarkable. Initial laboratory work demonstrated a mild leukocytosis with left shift (12.5 x 109/L, 76.9% neutrophils), and CT chest was significant for a large subcarinal mass measuring 5.5 x 2.6 cm causing mass effect on adjacent vessels and esophagus (Figure 1). Following an interdisciplinary discussion with IP, interventional radiology, and thoracic surgery, the decision was to proceed with mediastinoscopy for further evaluation. Intraoperatively, the subcarinal mass had thick fluid inside which grew Propionibacterium acnes (P. acnes). Fungal cultures, KOH stain, and AFB stain and culture were negative. Final histopathology showed fibroadipose tissue with fibrin, fat necrosis, and chronic inflammation consistent with abscess. There was no evidence of malignancy. Two weeks later, the patient continued to have a cough and repeat imaging showed a new 7.7 x 3.9 x 8.0 cm irregular, heterogeneous, air-containing mass in the superior medial right lower lobe concerning a lung abscess (Figure 1). The patient was admitted to hospital and begun on IV vancomycin and piperacillin-tazobactam and discharged on IV ampicillin-sulbactam. She was followed up in both IP and infectious diseases clinic 18 days later with significant improvement in symptoms and imaging. She was transitioned to oral amoxicillin-clavulanate for an additional month. Follow-up imaging after completion of antibiotics demonstrated near-resolution of the abscess (Figure 1).

PMC4756082_01

Female

A 46 year-old female presented with progressively worsening hearing on the right side, intermittent headaches and diplopia for the past 3 years and imbalance while walking for the past 5-6 months. She was bedridden since 15 days. She was unable to walk and requires support. There was no history of unconsciousness, convulsions or sphincteric complaints. There was no trauma or fever. There were no clinical features suggestive of neurofibromatosis. She had abdominal tuberculosis 10 years ago for which took full course of recommended antitubercular therapy. On examination, she was conscious, disoriented but obeyed all commands. Vision was apparently normal. She has bilateral sixth nerve paresis and right sensorineural deafness. Gag was normal. There was no motor deficit. She had right cerebellar signs. MR imaging of the brain showed a large right heterogeneously enhancing CP angle tumor, iso to hypo intense T1 and mildly iso to hyper intense on T2-weighted images suggestive of a vestibular schwannoma. The internal acoustic meatus (IAM) was not significantly widened and there was mild to moderate brainstem compression and moderate supratentorial hydrocephalus. A second lesion was seen in the right cerebellum in close proximity to the middle cerebellar peduncle. It was hypo intense on T2 MR imaging, peripherally enhancing with central area of necrosis and associated with extensive perifocal cerebellar edema suggestive of tuberculoma. There was similar small peripherally enhancing lesion in the pons as well. (Fig. 1A and B) She underwent a right retro sigmoid craniectomy. The cerebellum was bulging and slackened after CSF drainage from the cisterna magna. The caudal vestibular schwannoma was excised primarily. It was entirely solid, yellowish-gray, firm and vascular. The cranial nerves including seventh-eighth complex were preserved by intraarachnoidal microsurgical dissection. The tumor had not significantly widened the IAM. There were extensive arachnoidal adhesions of the tumor with the brainstem, cerebellum and nerves. Radical excision of the lesion was performed. Subsequently the intraaxial lesion was approached. A small corticectomy was performed over the right cerebellum and the lesion was encountered at depth of 2 cm. It was hard, gritty, avascular and well capsulated. The lesion appeared to be a tuberculoma and it was meticulously separated from the surrounding gliotic cerebellar tissue. A thin rim of gliosis separated this lesion from the lesion in right cerebello-pontine angle. The lesion was seen to extend into the middle cerebellar peduncle. A safe maximal excision was performed. Histological examination of the caudal and rostral lesions revealed a vestibular schwannoma and tuberculoma respectively. The patient received antitubercular chemotherapy and was serially monitored using MR imaging at 3-6 months interval. At follow-up after 3 years, the patient is well and has no neurological deficit. She is leading an active and independent life. At follow-up MR imaging after 3 years showed minimal stable residue in the right middle cerebellar peduncle. The lesion in the pons has considerably reduced in size. There is no mass effect. The vestibular schwannoma has been completely resected (Fig. 1C and D).

cerebello-pontine angle, collision, posterior fossa, schwannoma, tuberculoma

PMC8485840_01

Female

A 46-year-old woman with dermatomyositis diagnosed 5 months earlier, presented with a 1-month history of pain, warmth, redness and swelling localized to the metacarpophalangeal (MCP) joints and proximal interphalangeal (PIP) joints along with limitation of the movement of fingers and wrist. There was intermittent low-grade fever, occasional night sweats and recent onset of dry cough and loose stools over the past 1 week. Medications were prednisone 60 mg per day and mycophenolate mofetil (MMF) 1500 mg twice daily for the past 4 months, with hydroxychloroquine 200 mg twice daily added 2 weeks prior due to worsening symptoms of dermatomyositis including fatigue, as well as trimethoprim/sulfamethoxazole (TMP/SMX) 800/160 mg thrice weekly for Pneumocystis jirovecii prophylaxis. Patient was born and raised in the upper midwestern United States, married with four healthy children and worked as a corporate meeting planner. One year prior to presentation, the patient went camping and swam in a freshwater lake. There was occasional gardening prior to the diagnosis of dermatomyositis. There was no exposure to fish tanks. Travel was extensive throughout the US including Iowa, Illinois, California, Nevada, Arizona, Texas and Georgia. On physical examination, the patient appeared well and was not in acute distress. Blood pressure was 134/80 mm Hg, heart rate 77 beats per min, respiratory rate 18 breaths per minute and temperature 36.9 C. Examination of the left upper extremity noted swelling about the ulnar aspect of the left dorsal hand. There was pain with gentle range of motion about the ulnar aspect of left wrist and fourth and fifth MCP joints; no pain was elicited with gentle passive range of motion about any of the other joints of her left hand. There was no active synovitis in other joints. Sensation to light touch was intact in the median, ulnar and radial nerve distributions. A rash consistent with dermatomyositis was present on the chest, shoulders, forearm and dorsal aspect of both hands over the MCP joints (see Fig. 1). No open wounds were seen. All other systems were within normal limits. The white blood cell count was (range to ), and platelet count was (range to ). Sedimentation rate was 32 mm/h (range 0-29 mm/h), and c-reactive protein (CRP) was 52 mg/L (reference range 8 mg/L). Alanine aminotransferase was 77 U/L (range 7-45 U/L), aspartate aminotransferase was 28 U/L (range 28-43 U/L) and alkaline phosphatase was 51 U/L (range 37-98 U/L). QuantiFERON-TB Gold Plus was indeterminate, and human immunodeficiency virus (HIV) screen was negative. An X-ray of the chest was clear. An ultrasound of the left hand was notable for tenosynovitis of the left fourth dorsal compartment and subcutaneous edema of her dorsal left hand. On post-contrast T1-weighted fat-suppressed magnetic resonance imaging (MRI) of the left hand, there was peripherally enhancing tenosynovitis involving the extensor compartment (Fig. 2). There was no evidence of underlying septic arthritis or osteomyelitis. Orthopedic hand surgery was consulted. The patient underwent tenosynovectomy of the extensor tendons of the left wrist and hand along with irrigation and debridement. Upon exposing the extensor mechanism of the left hand, inflammation was noted in the fourth extensor compartment with edema and fluid but no frank pus (Fig. 3). Multiple specimens were sent for bacterial, fungal and mycobacterial cultures as well as Gram, fungal and acid-fast stains on fresh tissue. Surgical pathology from the tenosynovium revealed fibrinous exudate and severe chronic inflammation. Gram, fungal and mycobacterial stains on fresh tissue were negative. There was no growth on bacterial cultures. Fungal cultures revealed the growth of Histoplasma capsulatum at day six. Serology for Blastomyces, Aspergillus and Sporothrix were negative; Histoplasma serology and urine antigen were positive (Table 1). The patient was started on itraconazole 200 mg twice daily and was gradually being weaned off prednisone. There was a good initial response to antifungal therapy and itraconazole levels were within therapeutic range. Three months following the initial left hand debridement, the patient presented with a new nodule and a 1.2 cm fluid collection on the third MCP joint of the left hand; MRI was suggestive of worsening tenosynovitis (Fig. 4). Patient underwent additional irrigation and debridement; there was a thick rind of tissue around the extensor tendons of fourth and fifth compartments. Fungal smear of a fresh sample from the infected fluid collection showed many yeast forms; all of the fungal cultures remained negative. Surgical pathology was notable for necrotizing granulomatous inflammation but no fungal forms were noted on the surgical pathology specimens at that time. Itraconazole was continued. At 6 months after the initial debridement, the patient was weaned off steroids and mycophenolate and was started on monthly immunoglobulin therapy for dermatomyositis. Soon after completely discontinuing steroids at 6 months of antifungal therapy, the patient presented with weeping, nodular, white lesions along the surgical incision marks (Fig. 5). Urine Histoplasma antigen as well as serologies showed improvement (Table 1). Nevertheless, there was concern about possible clinical progression of the infection while on itraconazole. Dermatologic punch biopsy of one of these lesions revealed necrotizing granulomatous inflammation (Fig. 6) with small, budding yeasts seen on Grocott's methenamine silver (GMS) stain, consistent with Histoplasma (Fig. 7). An indium-labeled white blood cell scan did not reveal focal bone uptake in the left hand, although there was significant soft tissue uptake. The patient underwent repeat tenosynovial debridement and intraoperatively was found to have extensive inflammation and erosions of the fourth extensor compartment tendons in the dorsum of the left hand. Postoperatively, the patient was started on intravenous liposomal amphotericin B overlapped with oral delayed release posaconazole 300 mg per day. Treatment was complicated by severe electrolyte abnormalities, which prompted discontinuation of liposomal amphotericin B. Fungal cultures were negative yet again. Serum and urine Histoplasma antigen revealed stable low-level positives (see Table 1, at 6 months). There was a concern that the fistulizing tracks with tenosynovitis could represent immune reconstitution inflammatory syndrome (IRIS). In view of this, she was administered oral prednisone for suspected IRIS with a plan for a prolonged taper. TMP/SMX for Pneumocystis prophylaxis was re-started as well. After 4 weeks, posaconazole was changed back to itraconazole 200 mg twice per day due to cost issues. At the time of the patient's last follow-up, the suppurative and ulcerative lesions on the left dorsal hand, as well as the edema, had mainly resolved, leaving indurated violaceous scars (Fig. 8). A plan for a prolonged steroid taper was proposed in the setting of probable IRIS. The anticipated duration of therapy with itraconazole was 1 year assuming that the elevated serum and urine Histoplasma antigen levels completely resolved.

PMC3910236_01

Male

The 49-year-old patient was diagnosed with relapsing-remitting multiple sclerosis (RRMS) in 2006 that was initially treated with interferon beta-1a. Due to continuous relapse activity, the therapy was escalated to monthly natalizumab infusions in 2007. Thereafter, he had been stable with only one relapse in the first year of natalizumab treatment. In December 2012, he presented in our neurological emergency department with a progressive bilateral visual loss and slight confusion lasting for two weeks. Prior to admission he had been treated in a neurological practice with high dose methylprednisolone due to suspected relapse. On neurological examination, he demonstrated a previously described residual left-sided hemiparesis, pronounced in the left leg with brisk reflexes, an amaurosis of his right eye and markedly reduced vision of his left eye. The ophthalmological examination of the anterior segment of both eyes showed no inflammation. The posterior segment revealed an occlusive periarteriitis and a patchy necrotizing retinitis (Figure 1A-B). Besides the known non-active multiple sclerosis (MS)-typical lesions, the cranial magnetic resonance imaging (MRI) displayed multiple new dot-shaped cortical and subcortical lesions with diffusion restrictions that were not limited to a large-vessel vascular territory (Figure 2A-D). Neither these lesions nor the basal vessels revealed any contrast enhancement. Cerebrospinal fluid (CSF) analysis demonstrated a normal cell count, positive oligoclonal bands in the CSF (type 2), a total protein elevation of 0.87 g/L, an albumin quotient (CSF/serum) of 12.3 and varicella zoster virus (VZV) DNA was tested positive by PCR amplification. All other virological and microbiological CSF investigations were negative (antibody indices for CMV/HSV/VZV, CMV pp65 antigen, EBV antibodies and PCR, JCV PCR, HIV antigen ELISA, tuberculosis culture and PCR, aspergillus antigen ELISA, leptospirosis antibodies, cryptococcus antigen immunodiffusion, toxoplasmosis antibodies, borrelia antibodies, culture for neisseria and brucella and an unspecific culture for other pathogenic and non-pathogenic bacteria). Transesophageal echocardiography, electrocardiography, Doppler/duplex sonography of the deep leg veins and carotid arteries, coagulopathy screening, autoimmune antibodies (anti-neutrophil cytoplasmic antibody, anti-nuclear antibodies, ENA antibodies, anti-DNA antibodies, anti-NMDAR antibodies, anti-AMPAR antibodies, anti-LG1 antibodies, anti-CASPR2 antibodies, anti-GABAR antibodies, anti-phospholipid antibodies, anti-transglutaminase antibodies and anti-gliadin antibodies) and blood sedimentation rate were normal. As we suspected a vasculitis based on the fundoscopic examination and the MRI, we performed a digital subtraction angiography and a MRI-guided diagnostic brain biopsy of the parenchyma and the meninges. Both were carried out during the initial immunosuppressive and antiviral treatment due to the rapid progression of the visual loss. Neither the conventional angiography nor the biopsy showed definite signs of a vasculitis; however, the biopsy did not include deep white matter. For treatment of the VZV infection, aciclovir (800 mg three times a day iv for 14 days) was initiated. We also applied a high dose of intravenous methylprednisolone (1 g/day for five days followed by 2 g/day for five days) and subsequently an oral steroid (prednisolone 80 mg/day). Moreover, five cycles of plasma exchange therapy were performed to accelerate natalizumab clearance. After the steroid treatment and plasma exchange therapy, we applied a bolus of cyclophosphamide (500 mg/m2). In parallel, we treated the patient with acetylsalicylic acid (100 mg/day) and simvastatin (20 mg/day). Before transferral to the neurological rehabilitation clinic, he was almost completely blind and reported typical signs of a Charles-Bonnet syndrome with complex vivid hallucinations. At follow-up after two months, the CSF of the clinically stable patient showed a more than six-fold increase of intrathecal antibody indices against VZV from 0.900 at first presentation to 5.900, while the viral PCR results, including John Cunningham virus (JCV) PCR, were negative. The follow-up MRI after two and four months did not reveal any diffusion restrictions, whereas the dot-shaped lesions were persistently contrast-enhancing in contrast to the initial presentation. This was interpreted as an ongoing immune response related to the apparently still active vasculitis (Figure 2E-F). Therefore, the patient further received cyclophosphamide on a monthly basis. Since we assume that the infection associated vasculitis is a transient phenomenon and the active MS requires further long term treatment, it is planned to switch the treatment to teriflunomide.

PMC6062774_01

Female

A 55-year-old female presented to the emergency department for evaluation of severe lower flank pain radiating to her lower abdomen and chest. Further review of symptoms revealed that she also had cough, night sweats, chills, and an unintentional weight loss of 31 pounds over 3 months. Clinical examination was significant for bilateral axillary lymphadenopathy. Subsequently, a computed tomography (CT) scan of her chest, abdomen, and pelvis was performed that revealed extensive bilateral lymphadenopathy (above and below the diaphragm) as well as a new right upper lobe (RUL) thin-walled cavitary lung lesion with spiculated margins (Figure 1a). A positron-emission tomography (PET)-CT scan showed highly metabolically active lymphadenopathy in the neck, chest, abdomen, and pelvis but minimal to no PET avidity within the RUL cavitary lesion (Figure 1b). Axillary lymph node sampling showed moderate-to-large B-lymphocytes (positive for CD5, CD20, and cyclin D1), with fluorescence in situ hybridization positive for t(11; 14), consistent with MCL. Although a bone marrow biopsy revealed low disease burden (<10% involvement), her lymphoma demonstrated a high proliferation rate (Ki67 proliferation index 30%), and she was diagnosed with stage IV-B MCL. Prior to initiation of chemotherapy, she was referred to the pulmonary clinic for workup of the lung lesion, which was felt to have radiographic features atypical for lymphoma. She was an active, 30 pack-year smoker with symptoms of stable chronic bronchitis, sinusitis, and scant hemoptysis. Serum tuberculosis testing (TB-quantiferon) was negative. Although no prior self-history of cancer, she had a strong family history for cancer (lung cancer [father, paternal uncle, and paternal grandfather], cervical cancer [mother], and premenopausal breast cancer [paternal aunt]). Chest CT was significant for severe emphysema, multiple indeterminate pulmonary nodules, and a 1.7 x 1.1 cm, subpleural, thin-walled cavitary lesion with spiculated margins in the RUL (Figure 1a). Initial differential diagnosis included malignancy (primary/metastatic carcinoma and less likely lymphoma), subacute or chronic infections (such as tuberculosis and fungal infection), and vasculitis. Bronchoscopy was unremarkable, and bronchoalveolar lavage showed 87% macrophages, 10% neutrophils, and 2% lymphocytes, without malignant cells. Respiratory cultures grew 1+ Aspergillus flavus. Serum antineutrophil cytoplasmic antibodies and rheumatoid arthritis factor were negative. A short-interval (2 months) follow-up CT imaging showed stable pulmonary nodules but a persistent RUL cavitary lesion. A video-assisted thoracoscopic wedge resection was performed to exclude other diagnoses prior to initiation of chemotherapy for MCL. Pathological examination revealed a lepidic predominant, well-differentiated adenocarcinoma (pathological stage T1a), with coexistent foci of lymphoid infiltrates within and adjacent to adenocarcinoma (Figure 2a). The lymphoid infiltrate had histological features (convoluted irregular small nuclei; Figure 2b). By immunohistochemistry, the adenocarcinoma component was strongly positive with thyroid transcription factor-1, confirming pulmonary origin (Figure 2c) and discounting the possibility of metastasis from a possible mammary carcinoma. In addition, immunohistochemical profile (positive for B-cell markers CD20, pax5, and BCL1 [cyclin D1]; Figure 3a and b) was consistent with MCL. Multidisciplinary consensus was that no additional surgery, lymph node sampling, or adjuvant chemotherapy was needed. She was subsequently observed for both adenocarcinoma and lymphoma (high proliferation rate but with low disease burden), with surveillance imaging. A year later, however, she presented with dyspnea and a new right-sided pleural effusion (cytology positive for adenocarcinoma, negative for epithelial growth factor receptor/anaplastic lymphoma kinase). She received 6 cycles of carboplatin/pemetrexed/bevacizumab with good treatment response; however, she declined further maintenance therapy due to an intolerance of side effects. A few months later (a year ago), she presented with weight loss, chills, and night sweats, and CT imaging showed progressive lymphadenopathy concerning for MCL. She received ibrutinib and rituximab with good response initially; however, she could not complete the prescribed therapy due to side effects and was unfortunately lost to follow-up at the time of this writing.

cavitary nodule, collision histology, lung cancer, mantle cell lymphoma, non-hodgkin’s lymphoma

PMC7374225_01

Male

The four-year-old Caucasian male was first evaluated by genetics at 15 months of age given his history of global developmental delay. On examination, he was noted to have hypotonia and with craniofacial dysmorphism that included a thin vermillion of the upper lip, a broad nasal bridge, and deeply set eyes but with normal palatal morphology. By 16 months of age, he underwent gastrostomy tube placement for severe dysphagia. Given the persistence of seizure-like spells with electroencephalograms (EEG) that revealed epileptiform discharges, he was started on levetiracetam at 3.5 years of age. This medication was weaned off at 5 years of age given the lack of clinical correlation between spells and EEG data. Over time, patient developed taurodontism and maloclussion, while bone density scan documented osteopenia at 4 years of age. Extensive evaluation for potential underlying abnormalities included brain and spinal imaging, the SNP chromosomal microarray analysis, spinal muscular atrophy molecular testing, SNRPN methylation, and fragile X testing, all within normal limits. The clinical exome sequencing analysis of 4616 genes revealed a de novo heterozygous pathogenic variant in SATB2 (NM_015265.3 : c.1285C > T (p.R429*)). The child presented for initial evaluation in our outpatient child and adolescent psychiatry clinic for ongoing sleep and behavioral problems. Since the patient was nonverbal, the history was obtained primarily from his parents. During the initial evaluation, his parents reported that his sleep problems started around the age 2.5 years, with chronic maintenance insomnia. He would initiate sleep between 11 and 11:30 pm but would wake up around 4 am most mornings and would stay awake. He would sometimes take a nap for about an hour, either around 8-9 am or, once he started school, between 12 and 1 pm. There was no evidence of other kinds of sleep problems, including parasomnias, sleep-breathing disorders, restless leg syndrome, or sleep eating. His behavioral problems included climbing on parents lap and upper torso, claw/scratch their face or limbs, pull family members' hair, flap/clap his hands when excited, climb up on furniture, knock over objects, and kick and scream, especially when he would get bored or frustrated. He was unable to accurately assess his environment and was unaware of dangerous situations; for example, he would walk on to the street or walk into a pool. His medications at the time of initial presentation included levetiracetam 250 mg twice daily, clonidine 0.1 mg at bedtime, and melatonin 5 mg at around 8 pm (Figure 1). He was also on over the counter calcium and vitamin D (400 IU daily) supplements, iron supplements, fish oil (omega-3), bone broth, sage (Salvia officinalis), and cannabidiol (CBD) oil off and on. He received all his medications and supplements through his G-tube. A multispecialty team evaluation at around age 3 determined that he did not have autism spectrum disorder (ASD). He could not participate in the behavioral therapy due to not having access to specialized therapists who could work with nonverbal children. He did receive speech, occupational, and physical therapy and was working on learning a picture-based communication system. He also had a history of previous tonsillectomy and pressure equalization (PE) tubes. He did not have a history of a mental health disorder or abuse/maltreatment/neglect but did have a family history positive for anxiety and depression. Given his continued sleep and behavioral problems, his clonidine was gradually increased from 0.1 mg at bedtime to 0.1 mg three times daily, and he was eventually started on trazodone, which was gradually increased to 75 mg at bedtime. Appropriate sleep hygiene education was given to parents, which they implemented. At this time, he averaged about 5-6 hours of nighttime sleep with 1.5-3 hour nap during the afternoons, but there were some nights that he only slept an hour. His behaviors improved some with less climbing and clawing at them; however, he started to "whine" a bit more and hit himself with his fists. Since he appeared a little stable with his sleep, parents tried to get him to sleep in his own toddler bed, which was attached to their bed; however, this did not sustain. An overnight polysomnogram at 4 years of age ruled out central or obstructive episodes of sleep apnea but showed reduced sleep efficiency (82%, normal >90%) and increased arousal index of 14.9 per hour (normal <10/hour). He was also started on ferrous sulfate 5.5 mL twice daily due to low ferritin levels (49.8 ng/mL). Since he continued to wake up around 4-4:30 am, we tried splitting his total dose of trazodone, which did not work as well, so his dose was consolidated to trazodone 150 mg at 10 pm. His neurologist also started him on cyproheptadine 4 mg three times daily for headaches, but this was discontinued a month later due to lack of effectiveness. Patient started prekindergarten at his new school by this time and was falling asleep in the mornings, so we decided to decrease the daytime dose of clonidine to 0.05 mg every morning and noon, while continuing with the bedtime dose at 0.1 mg. Trazodone was further increased in a step-wise manner to 300 mg given at 10 pm. He also started having daytime episodes of screaming for hours at a time, which parents described "as if he was hurting," without any apparent reason. He was started on quetiapine 25 mg as needed for these screaming/agitated episodes, which was initially occurring once every other week. However, these worsened in frequency to daily episodes, and since quetiapine appeared to calm him down, he started receiving quetiapine 25 mg daily at around 4 pm, which was further increased to 50 mg due to lack of effect from the previous dose. He is G-tube fed, so parents control his caloric intake given the increased risk of metabolic syndrome due to weight gain with quetiapine. To monitor for side effects, his height and weight was regularly monitored during clinic visits. Periodic lab work including sodium, calcium, and phosphorous levels, vitamin D levels, hepatic and renal function, and glucose have been within normal ranges.

PMC8082984_01

Female

In April 2020, an 83-year-old Caucasian woman was admitted to the emergency room because of easy bruising, epistaxis, and gum bleeding. She also reported bloody urine and stools on one occasion. Laboratory exams performed on the day prior to admission revealed both thrombocytopenia (2000 mm3) and anemia (7.2 g/dl). The patient denied a personal or family history of bleeding and anemia and previous complete blood counts (CBCs) were normal. Her past medical history was unremarkable, and she did not take any medications except nebivolol for hypertension. However, 20 days prior to admission she developed fever, myalgia, and dyspnea, which were treated with azithromycin (5-day course). In April, there was a COVID-19 outbreak in Italy, but the patient denied close contact with confirmed or suspected cases of COVID-19. On examination, body temperature was 36.5 C. Oxygen saturation was 97% in room air, but then fell to 90%, and oxygen was administered through a nasal cannula (2 L/min). Diffuse ecchymosis on the skin and petechiae on the lips, oral cavity, and both lower limbs were observed. The rest of the physical examination was normal except for diminished breath sounds and rales at both lungs. Laboratory exams (Table 1) showed anemia, thrombocytopenia, leukocytosis, and lymphocytopenia. Levels of C-reactive protein (CRP), lactate dehydrogenase (LDH), and fibrinogen were increased, while prothrombin time, partial thromboplastin time, and procalcitonin levels were in the normal range. No blasts, schistocytes, or platelet aggregates were found on repeated peripheral blood smears. A brain computed tomography (CT) scan revealed a left cortical microhemorrhage (5 mm). Moreover, chest CT showed bilateral consolidations and multiple patchy ground-glass opacities with peripheral distribution, suggesting COVID-19 pneumonia. However, molecular testing for SARS-CoV-2 was negative on two nasopharyngeal swabs (Diasorin assay). The patient was treated with two pools of platelets and a unit of packed red blood cells, intravenous prednisone (1 mg/kg), immunoglobulin (IVIG 400 mg/kg), antibiotics, and then transferred to our internal medicine ward. Reticulocytosis, haptoglobin consumption, and increased both LDH and indirect bilirubin suggested hemolytic anemia. The D-dimer value was elevated; however, normal antithrombin III activity, absence of both schistocytes and ADAMTS13 inhibitors, and normal ADAMTS13 activity made a diagnosis of thrombotic microangiopathy unlikely. Doppler ultrasound of both upper and lower extremities excluded venous thrombosis. Flow cytometry for CD55/CD59 including fluorescein-labeled proaerolysin (FLAER), triglycerides, ferritin, complement, anti-cardiolipin and anti-beta2-glycoprotein I antibodies were normal/absent, making paroxysmal nocturnal hemoglobinuria (PNH), hemophagocytic syndrome, and antiphospholipid syndrome (APS) unlikely. The direct antiglobulin test (DAT-IgG and C3D) and testing for irregular antibodies were negative, while anti-platelet antibodies were present. Screening for viral infections (HIV, hepatitis B virus (HBV)/hepatitis C virus (HCV), cytomegalovirus (CMV), Epstein-Barr virus (EBV), parvovirus-B19) and autoimmunity was negative except for subclinical hypothyroidism. A bone marrow (BM) biopsy could not be performed because of the high bleeding risk, but peripheral blood cytometric immuno-phenotypic analysis was normal, although the absolute number of CD4+ T cells was reduced (369/mm3, normal range: 493-1666). The patient continued treatment with IVIG (5 days), oral prednisone (1-1.5 mg/kg), and platelet transfusions. Hemoglobin levels increased progressively, while thrombocytopenia did not respond to treatment (Figure 1). Moreover, a follow-up brain CT scan performed on day 5 showed the development of a thin frontal subdural hematoma. Meanwhile, a further molecular test for SARS-CoV-2 on sputum (Seegene's Allplex 2019-nCoV assay) confirmed the diagnosis of COVID-19 and the patient was transferred to a COVID-19 ward and treated with COVID-19 standard therapy. In the COVID-19 ward the patient was treated with oxygen therapy and she did not undergo anti-viral treatment. On day 6, treatment with the oral thrombopoietin receptor agonist (TPO-RA) eltrombopag was initiated (starting dose: 25 mg/day, maximal dose: 75 mg/day). The patient did not report any side effects and liver function remained unchanged. In the following days, the platelet count progressively increased (Figure 1) and the subdural hematoma resolved spontaneously. On day 24 after admission, the platelet count was normal and two consecutive nasopharyngeal swabs for SARS-CoV-2 were negative. The patient was discharged from the hospital on tapering doses of eltrombopag (50 mg/day) and prednisone (25 mg/day). At the follow-up visit 15 days after hospital discharge, the patient was asymptomatic, and the platelet count was in the normal range.

covid-19, case report, eltrombopag, hemolytic anemia, immune thrombocytopenia

PMC5925959_01

Male

A 79-year-old male with PMH of Hypertension and Diabetes presented to the ED after developing progressively worsening shortness of breath and mid sternal pleuritic chest pain during a trans-continental flight, and was in mild respiratory distress by the time EMS evaluation occurred. In the ER chest x-ray suggested a large right hydro pneumothorax with moderate left sided pleural effusion (Fig. 1), which was confirmed by chest CT (Fig. 2, Fig. 3). Both large-bore and small-bore chest tubes were placed, which resulted in symptomatic improvement. Due to the unclear etiology, the patient was started on broad spectrum IV antibiotics for suspected pneumonia. Pleural fluid analysis was remarkable for an exudative pattern that was negative for malignant cells (Table 1). When infections etiologies as well as a Tuberculosis etiology were ruled out, antibiotics were discontinued. The small-bore catheter was eventually removed, however the chest tube remained due to the recurrence of pneumothorax on imaging studies. While the patient initially experienced clinical improvement requiring only minimal supplemental oxygen, he soon developed recurrence of bilateral pleural effusions with clinical deterioration. This pattern persisted, and serial pleural cytology samples were remarkable for bloody fluid with elevated cellularity, proteins and LDH, but were negative for malignant cells. As infectious and inflammatory etiologies were ruled out as the cause of recurrent hydro-pneumothorax, video-assisted thoracoscopy (VATS) and pleural biopsy confirmed the diagnosis of malignant pleural mesothelioma-epithelioid variant-in the context of histologic findings (Fig. 4, Fig. 5) and imunohistochemical markers positive for calretinin, CK 5/6, mesothelin and focal Glut-1 and negative for EpCam, CEA, Napsin A, TTF-1, and BerEP4. Interestingly, mesothelial plaques were restricted to the parietal pleural surface without invasion of the chest wall or extension into the contralateral pleura. Given the imaging and tissue staging, chemotherapy was recommended, however prognosis remained reserved due to the patient's poor functional status. Ultimately, this patient opted not to pursue aggressive measures, and was discharged home with provisions for comfort care, and expired 3 months later.

hydro-pneumothorax, hydrothorax, malignant pleural mesothelioma, pneumothorax

CT Chest coronal view showing right sided hydro-pneumothorax and left sided pleural effusion.

PMC7184854_01

Male

An 81-year-old man was admitted due to massive upper gastrointestinal hemorrhage for 2 h. He had epigastric pain and early satiety for 3 weeks. His past medical history was unremarkable except for heavy alcohol drinking, 1-2 bottles a day for over 30 years. He denied a history of exposure to thorotrast or vinyl chloride. Physical examination revealed mildly pale, icteric sclerae, hepatomegaly with a liver span of 14 cm, parotid gland enlargement and palmar erythema. Other examinations were unremarkable. Laboratory investigations on admission showed white blood cell (WBC) count 6,210/dL, hemoglobin (Hb) 5.8 g/dL, platelet count 283 x 103/dL, aspartate transaminase (AST) 116 U/L, alanine aminotransferase (ALT) 73 U/L, alkaline phosphatase (ALP) 192 U/L, albumin 2.7 g%, total bilirubin (TB) 5.74 mg%, direct bilirubin (DB) 5.3 mg%, prothrombin time (PT) 16.2 s (control 12.4), and international normalized ratio (INR) 1.23; serum alpha-fetoprotein (AFP) was within normal range. Esophagogastroduodenoscopy was performed and revealed a 3-cm large ulcer with elevated border and necrotic tissue in the antrum of stomach; no varix was seen. The tissue biopsy was performed to exclude malignant ulcer. Liver ultrasonography revealed a cirrhotic liver and diffused multiple echogenic nodules size 7-9 mm in both lobes with a large echogenic mass 3.3 cm in size with a halo. A further CT scan demonstrated multiple large infiltrative masses with few arterial enhancements, no venous washout, size 1-4 cm in both lobes, osteolytic foci at the thoracic spine level T10 and T11, and small subpleural nodule at the right lower lung. Liver biopsy was performed for definite diagnosis. The specimen consisted of a few pieces of gray tan irregular soft tissue and disclosed the angiosarcoma; immunohistochemical study showed positive staining for CD34 and factor VIII. The specimen of gastric ulcer biopsy also revealed metastasis of angiosarcoma. He was treated with a paclitaxel dose of 175 mg/m2. Unfortunately, 5 days after receiving chemotherapy, he developed febrile neutropenia with septic shock. His relatives refused further treatment and invasive procedures, and he died in the following days.

hepatic angiosarcoma, intra-tumoral hemorrhage, primary hepatic angiosarcoma

PMC7184854_02

Female

A 55-year-old woman with a medical history of type 2 diabetes mellitus, presented with right upper abdominal pain and significant weight loss for 5 months, and progressive jaundice for 2 months. She denied a history of carcinogen exposure. Physical examination showed hepatomegaly 4 cm below the right costal margin with a liver span of 15 cm. Liver examination described a rubbery to firm consistency, blunt edge, and smooth surface. Other findings were unremarkable except mild icteric sclerae. The complete blood count revealed: WBC 9,820/dL, Hb 12.0 g/dL, and platelet count 98 x 103/dL. The liver function test showed: AST 44 U/L, ALT 20 U/L, ALP 449 U/L, TB 3.81 mg%, DB 2.57 mg%. The serum AFP was 2.16 ng/mL (normal <7 mg/mL). Multiphase CT scan demonstrated diffused multiple arterial enhancing infiltrating nodules varying in size, scattered throughout the entire liver, with ascites and mesenteric fat reticulation suspicious of carcinomatosis peritonei. Laparoscopic liver biopsy was performed for diagnosis, and the specimen consisted of a piece of light brown irregular soft tissue. Histopathological findings showed the presence of diffused proliferation of abnormal small vessels with diffused hemorrhage. The abnormal vessels showed enlarged endothelial cells with nuclear atypia. Immunohistochemical study showed positive staining for CD34 and factor VIII in the endothelial cells. Histopathological study was consistent with PHA (Fig. 1). She received a total of five cycles of paclitaxel with a 20% dose reduction. The following posttreatment CT scans showed progression of the disease with peritoneal metastasis, and she later decided to stop treatment. She survived for 19 months and 14 months after symptom onset and treatment initiation, respectively.

hepatic angiosarcoma, intra-tumoral hemorrhage, primary hepatic angiosarcoma

PMC7184854_03

Female

A 47-year-old woman without past medical history was admitted due to acute right upper abdominal pain for 8 h and syncope prior to admission. She had a history of taking oral contraceptive pills 4-6 months per year, for 7 years. Physical examination revealed vital signs: BP 100/60 mm Hg, pulse rate 115/min. Her body mass index was 33.6 kg/m2. Abdomen examination showed marked tenderness at the right upper quadrant; the liver was palpated 8 cm below the costal margin with a liver span of 20 cm with mild tenderness, no splenomegaly, and no shifting dullness. Laboratory investigations showed: WBC count 8,200/dL, Hb 7.4 g/dL, and platelet count 592 x 103/dL, AST 34 U/L, ALT 23 U/L, ALP 335 U/L, TB 1.22 mg%, DB 0.73 mg%; coagulogram was in normal limit, AFP was 2.72 ng/mL. The emergency CT scan revealed acute rupture of liver tumor by evidence of acute clot and acute hematoma. She was provisionally diagnosed with ruptured hepatic adenoma and underwent emergency hepatic embolization. The angiography finding revealed a large hepatic mass at the anterior aspect of the right hepatic lobe, receiving arterial supply from the anterior branch of the right branch of the hepatic artery. Eventually, embolization was performed to stop bleeding. The scheduled CT scan 2 weeks after embolization showed a larger diameter of hemorrhagic mass from 20.7 to 23.0 cm, lysed perihepatic hematoma, without distance metastasis (Fig. 2). Four weeks after embolization, she underwent extended right hepatectomy with wedge diaphragm and primary repair. The operation demonstrated a huge liver mass with intratumoral hemorrhage, displaced IVC, and mediastinum. The specimen consisted of a liver tumor size 28 x 20 x 14 cm and weighing 2,300 g. The tumor appeared to be a light-brownish rubbery mass with a massive hemorrhage. The histopathological finding was compatible with angiosarcoma (French system grade III) and free tumor margin. The immunochemical staining was positive for CD34 and factor VIII, consistent with PHA (Fig. 3). The follow-up CT scan was performed after surgery, and it showed multiple new nodules about 0.5-2 cm in the left lobe liver, a heterogenous enhancing mass size 3.7 cm in the right subdiaphragmatic space; peritoneal thickening was also noted. Thus, the physicians planned to treat her with chemotherapy, doxorubicin. However, she refused chemotherapy treatment because of her poor clinical condition, and she passed away 4 months later.

hepatic angiosarcoma, intra-tumoral hemorrhage, primary hepatic angiosarcoma

PMC7184854_04

Female

A 69-year-old previously heathy woman presented with left upper quadrant pain for 2 months. She described her intermittent colicky abdominal pain, each attack lasting 10 min. She also noticed a weight loss of 3 kg in a week. Physical examination showed palpated liver 4 cm below the right costal margin and 6 cm below the xyphoid; the surface of the liver appeared to be lobulated with firm consistency; no hepatic bruit was heard. The laboratory investigation showed: WBC count 5,080/dL, Hb 10.5 g/dL, and platelet count 99 x 103/dL, AST 84 U/L, ALT 33 U/L, ALP 187 U/L, TB 2.47 mg%, DB 1.48 mg%, PT 20 s and INR 1.89. The serum tumor markers included AFP, CEA, and CA 19-9 and were within normal limits. The scheduled CT scan demonstrated numerous masses, and multiple nodules size 1-9 cm across the entire liver, an osteoblastic lesion at L4 vertebrae, multiple small nodules 2-8 mm in size at both lungs with surrounding ground glass, which is typical for hemorrhage (Fig. 4). For a definite diagnosis, she underwent real-time sonographic guidance percutaneous tumor biopsy. The specimen consisted of light brown soft tissue. The histopathological finding revealed a malignant vascular tumor, immunochemistry staining positive for CD 34 and factor VIII. These findings are consistent with angiosarcoma. The patient had planned to have chemotherapy. Unfortunately, 2 weeks after diagnosis, she was admitted to the hospital due to severe abdominal pain. Investigations revealed a ruptured tumor, evidence of disseminated intravascular coagulopathy, and liver failure. Thus, she denied invasive therapy and passed away 1 week later. The clinical manifestation, tumor feature, and treatment outcome of the four patients are summarized in Table 1.

hepatic angiosarcoma, intra-tumoral hemorrhage, primary hepatic angiosarcoma

PMC8024703_01

Female

An 82-year-old woman was admitted to the Department of Cardiovascular Medicine at Hamanomachi Hospital for treatment of atrial fibrillation. She complained of exertional dyspnea spanning four months. Her medical history included end-stage renal failure of unknown etiology and maintenance dialysis for two years. Her medication included 2.5 mg of bisoprolol. She had a temperature of 36.5 C, blood pressure of 95/59 mmHg, a heart rate of 68 beats per minute, oxygen saturation of 98% under room air. Physical examination revealed slight late inspiratory crackles in both sides of her chest with no peripheral edema. Multiple nodules and tooth indentation were noted on the tongue (Fig. 1). An echocardiogram showed a decreased left ventricular ejection fraction of 41%. Myocardial biopsy was performed, but there were no specific features. The patient underwent electrical cardioversion, and the atrial fibrillation returned to sinus rhythm. The patient was then referred to the Department of Respiratory Medicine for abnormal chest imaging. High-resolution CT of the chest revealed diffuse ground-glass opacities (GGO) with mosaic attenuation, consolidation in the left lingular lobe, and subpleural, wedge-shaped nodules in the bilateral lower lobes (Fig. 2). To facilitate diagnosis, bronchoscopy was performed. Bronchoscopy revealed enlarged tortuous submucosal vessels at the main carina and left main bronchus (Fig. 3), suggesting tracheal amyloidosis. A transbronchial lung biopsy (TBLB) of the left lingular lobe was performed. Microscopic examination of the TBLB showed deposition of amorphous eosinophilic amyloid at the smooth muscle layer of the bronchial tissue (Fig. 4A). Congo red staining displayed a positive signal in polarized light (Fig. 4B and C). Immunohistochemical staining for amyloid P was positive (Fig. 4D). No pathogen or malignancy was detected. From these findings, she was diagnosed with pulmonary amyloidosis. Bronchoalveolar lavage fluid from left B3 was brownish-yellow and numerous hemosiderin-laden macrophages were detected with Berlin blue staining (Fig. 5), indicating chronic alveolar hemorrhage, resulting in pulmonary hemosiderosis. Cytology of the lavage showed alveolar macrophage predominance (99% macrophages and 1% neutrophils). Additional serological examinations to evaluate the etiology of pulmonary hemorrhage causing hemosiderosis, anti-neutrophil cytoplasmic antibody (ANCA), antinuclear antibody (ANA), and rheumatoid factor (RF), were negative. Therefore, pulmonary hemosiderosis was considered related to pulmonary amyloidosis. An upper gastrointestinal endoscopy was also performed, and a duodenal biopsy confirmed amyloidosis. In addition, A CT of the body showed soft tissue masses around the hip joints, which were thought to be amyloidosis lesions. These findings suggested systemic amyloidosis. To investigate the etiology of amyloidosis, further serological examinations were performed. Serum IgG, IgA, and IgM levels were low (380 mg/dL, 19 mg/dL, and 4 mg/dL, respectively). Serum free light-chain analysis showed greatly increased lambda light chain of 28,900 mg/L with kappa light chain of 36.8 mg/L. Serum immuno-electrophoresis showed a monoclonal lambda light-chain peak, and urinary Bence-Jones protein was positive. Suspecting multiple myeloma, bone marrow examination was performed. Bone marrow examination showed plasma cell neoplasms with lambda light-chain restriction. Flow cytometry analysis of bone marrow cells revealed a CD19-CD38highCD45-CD56+CD138+cyLambda+ cell population, which is a typical immunophenotype of myeloma cells. This confirmed the diagnosis of multiple myeloma, lambda light chain type, international staging system Stage 3. Chemotherapy of bortezomib, lenalidomide and dexamethasone was initiated, followed by oral ixazomib, lenalidomide, and dexamethasone. Six months after diagnosis, she is still receiving chemotherapy on an outpatient basis.

amyloid tongue, multiple myeloma, pulmonary amyloidosis, pulmonary hemosiderosis

Radiological findings of the patient. (B) Chest CT images on admission showing diffuse ground-glass opacities (GGO) with mosaic attenuation, consolidation in the left lingular lobe (arrow), and subpleural, wedge-shaped nodules in the bilateral lower lobes (arrowhead).

PMC523858_01

Male

The 36 year- old male patient, after receiving CAPD treatment for 4 months, consulted our clinic because of stomachache, diarrhea, nausea, vomiting and continous fever. The patient had been diagnosed with chronic renal deficiency and had been followed up with diagnosis of predialysis CRF for 4 years. The patient was referred to us because of his symptoms such as of nausea, vomiting, weakness, and a general condition of fatigue. Immediate care involved an urgent hemodialysis followed by CAPD and planning for renal replacement therapy. Through a physical examination, the patient's blood pressure was 110/70 mmHg. The general condition was bad and pulmonary sounds in the respiratory system were diminished slightly in lower zones. On CAPD catheter's entering segment, infections were not seen. In a laboratory investigation Hg was at 9.1gr/dl, Htc was at %27.6, WBC was at 5200/mm3, the platelet count was at 203000/mm3, and the erythrocyte sedimentation rate was at 22 mm/h. In biochemical findings, furthermore, serum creatinine was at 6.05 mgr/dl [ref. 0,5-1,4], urea nitrogen was at 38 mgr/dl [ref.5-20], protein was at 3.8gr/dl [ref:6-8.5], albumin was at 1.2 gr/dl [ref:3,5-5], and lactic dehidrogenase was at 565 iu/L. Serum sodium, potassium, glucose, bilirubin, alkaline phosphatase, aspartate and alanine aminotransferase, gamma-glutamyl transpeptidase, amylase, triglyseride, and cholesterol were normal. A coagulation factor protrombin time was found to be 18.7 sn. C-reactive protein was 9.54 mgr/dl. Bilateral costofrenic angles were blunted in posteroanterior pulmonary graphy. No parasites and cystes were found in fecal examination due to diarrhea. No pathogenic agent was detected in stool cultures. In peritoneal cell counting, 1600/mm3 cell were detected and it was seen that 70 percent of these cells were polymorphonuclear leukocytosis (PMNL). The patient was given ceftazidime (IV), cephazol, and amikacin (intraperitoneal), but no benefit was noticed after 12 days of antibiotherapy and there was no growth in peritoneal fluid cultures. There were PMNL present but no microorganism could be detected. Acid-fast basilli (AFB) was found to be positive in the gram staining of peritoneal fluid in the remaining follow up periods, and the patient had begun antituberculosis therapy in fours(with isoniazid, rifampin, ethambutol and pyrazinamide). Tuberculin skin test was anergical. On the 15th day of anti tbc therapy, peritoneal fluid cell count decreased to 300/mm3 . Peritoneal fluid bacterial culture, blood cultures, throat culture and urine culture were negative but peritoneal fluid tbc culture was found to be positive, in Lowenstein- Jensen medium in 24 days. The patient was followed up with the treatment for recovery with an anti-tbc treatment. The peritoneal fluid of the patient was sent to be examined with Gram staining and Ziehl Neelsen staining. The peritoneal fluid was centrifuged at 3,000 x g for 15 minutes and the sediment was stained by Gram and Ziehl-Neelsen staining. The Gram staining showed PMNL presence but no microorganisms. The Ziehl-Neelsen staining(AFB) was positive. The peritoneal fluid was transferred to 10 ml sterile glass tube and centrifuged at 3,000 x g for 15 minutes. The concentrated sediment was inoculated onto Lowenstein Jensen (LJ) medium without prior decontamination. LJ medium was incubated at 37 C. Two specimens were later sent to be examined with Ziehl Neelsen staining on two different days. Both of them were detected to be positive for Ziehl Neelsen staining. LJ medium was examined for growth twice weekly for the first two weeks and once a week thereafter until the eighth week. After 24 days, the colonies were able to be seen on LJ medium. Positive growth was confirmed by Ziehl Neelsen staining.

PMC7654305_02

Male

A 41-year-old male working in information and technology, admitted to the hospital on 2 July 2020 with chief complaints of nervousness and worrying thoughts for 5 months, easy irritability for 3 months which aggravated for more than 1 month. The patient caught a cold during the COVID-19 outbreak and was feverish with a body temperature of 37.1 C. The patient feared that he contracted COVID-19, but the PCR and lung CT investigations were normal. The patient was still not assured and had symptoms of palpitation, chest tightness, shortness of breath, tremor, bodily discomforts, restlessness, lack of concentration, weight loss of more than 10 pounds, and poor sleep. Social functioning was markedly impaired. On 18 June, the patient was treated with antidepressants and benzodiazepines in another hospital. Patients feared that the medication would stop working itself. He was kept on an antidepressant and benzodiazepine treatment after admission. The symptoms of anxiety improved while the patient was admitted to the hospital. Patients considered the hospital environment to be clean and safe and he was afraid to leave the hospital. The patient feared contracting coronavirus from the passers-by and the fear was not improved with medications. VR exposure therapy was started on July 4. There was a rapid improvement after two exposures. The patient was discharged on July 16, 2020. After being discharged from the hospital, the patient quickly returned to normal social life and work. During follow-up, the self-reported anxiety symptoms had largely disappeared. The patient worried about novel coronavirus but there was no impairment in daily activities and work.

covid-19, vret, exposure therapy, phobia, telehealth, telemedicine

PMC6129347_01

Male

A 20-year-old male with no past medical history presented with acute hypoxic respiratory failure requiring intubation. CT scans revealed a 9.1 x 7.3 cm mediastinal mass encasing the aortic arch with extension into the lower neck resulting in tracheal deviation. Laboratory evaluation demonstrated a white blood cell count of 2.5 x 109/L with 78% blasts on differential, hemoglobin 7.1 g/dL, and platelets 51 x 109/L. Bone marrow evaluation revealed a hypercellular marrow with 98% blasts by morphology. By flow cytometry, blasts expressed CD34, CD117, CD33, CD38, CD56, and CD7 and lacked expression of myeloperoxidase (MPO) and monocytic markers. A subset of blasts expressed low levels of cytoplasmic CD3 although subsequent assessment by immunohistochemistry for CD3 was negative. The blasts were negative for CD2, CD4, CD5, CD8, CD19, and cCD79a. Cytogenetic analysis revealed 10 metaphases with a complex karyotype including rearrangement of chromosome 4, loss of chromosomes 12 and 13, and a rearrangement between chromosome 13 and 1-2 unidentified markers. Molecular testing was positive for a FLT3-ITD mutation. A fine needle aspiration of the mediastinal mass demonstrated acute leukemia with an immunophenotype similar to that of the bone. T-cell gene rearrangement analysis by PCR on the mediastinal biopsy showed no evidence of clonal T-cell gene rearrangement. While it was difficult to assign a definite lineage for this acute leukemia, diagnostic considerations included acute myeloid leukemia (AML), T-ALL, and mixed phenotype acute leukemia T/myeloid (MPAL). To meet criteria for MPAL T/myeloid, blasts must express lineage-defining markers for both T and myeloid lineages. This acute leukemia lacked MPO as well as monocytic markers and therefore did not meet criteria for the myeloid component of MPAL T/myeloid. While flow cytometry demonstrated weak cytoplasmic CD3 on the blasts suggestive of T-lineage differentiation, this could not be confirmed by immunohistochemical stains. Additionally, the blasts lacked expression of CD2, CD4, CD5, CD8, and CD1a. Therefore, a diagnosis of AML, NOS was initially favored. The patient was induced with daunorubicin in combination with high-dose cytarabine and achieved complete remission (CR). He was consolidated with 2 cycles of high-dose cytarabine and in light of the FLT3-ITD mutation, sorafenib was added. Because his leukemia was considered "poor-risk" given the extramedullary disease at presentation, complex karyotype, and FLT3-ITD mutation, he underwent a 7/10 haploidentical allogeneic hematopoietic cell transplant (alloHCT) from his father in first remission. Conditioning included fludarabine, cyclophosphamide, and low-dose total body irradiation as per the standard Hopkins regimen. Prior to alloHCT, multiparameter flow cytometry from the University of Washington showed no evidence of measurable residual disease (MRD). Posttransplant immunosuppression consisted of cyclophosphamide, tacrolimus, and mycophenolate mofetil. A bone marrow biopsy and restaging PET CT at approximately day +60 confirmed an ongoing CR and 100% donor chimerism in the CD3, CD14/15, and CD19 compartments. For posttransplant maintenance, he received 6 cycles azacitidine (given daily for 5 days at 32 mg/m2 in 28-day cycles):initiated at approximately day +100:followed by maintenance sorafenib 200 mg twice daily. His tacrolimus was discontinued at approximately 6 months posttransplant with no evidence at any point of either acute or chronic graft-versus-host disease (GVHD). At 13 months posttransplant, he developed progressive neutropenia. Bone marrow evaluation revealed relapsed leukemia with 42% blasts expressing a slightly different immunophenotype than that of his original disease (CD117-negative and CD5-positive). Immunohistochemical stains on the core biopsy demonstrated that blasts were positive for CD34, TdT, CD5, and CD7, with a small subset that was weakly positive for CD3. Cytogenetic studies demonstrated a complex karyotype similar to that of his original leukemia. FLT3-ITD PCR was negative but extended mutational testing:not previously performed:revealed mutations in FBXW7, NOTCH1, and EZH2, all of which are recurrently mutated in T-ALL. Additionally, bone marrow chimerism studies showed for the first time a decline in CD3 donor chimerism from 100% to 91%. Based on emerging data to support the use of venetoclax in T-ALL, he began salvage therapy with venetoclax (given daily, initially at 800 mg then dose reduced to 400 mg due to the interaction with his azole for fungal prophylaxis) in combination with decitabine (given daily for 5 days at 20 mg/m2 in 28-day cycles). After 2 cycles, his peripheral blood counts had normalized, formal CR criteria were met, and a restaging bone marrow evaluation demonstrated no morphologic evidence of residual leukemia. MRD assessment:again performed via multiparameter flow cytometry at the University of Washington:also showed no evidence of persistent disease. CD3 chimerism in the bone marrow was restored to 100% donor. In light of the lymphoid origin of his relapsed leukemia, next generation sequencing (NGS) was performed (ClonoSEQ, Adaptive Biosciences) on his relapse specimen, identifying a dominant T-cell receptor (TCR) clone comprising 8.249% of total nucleated cells. We retrospectively also assessed his original diagnostic bone marrow specimen and found that the same TCR clone was present in 11% of total nucleated cells. MRD assessment from a bone marrow specimen after 2 cycles of venetoclax and decitabine:also via ClonoSEQ:showed no detectable residual leukemia at a sensitivity of 1 leukemic cell per 106 cells. He received a total of 5 cycles of decitabine and venetoclax, with intermittent dose interruptions of venetoclax due to neutropenia. He remained MRD negative via multiparameter flow cytometry and ClonoSEQ and subsequently underwent a second haploidentical alloHCT with fludarabine, cyclophosphamide, and low-dose TBI conditioning. Decitabine and venetoclax were discontinued shortly prior to the second haploidentical alloHCT. He achieved full donor chimerism at day +18 posttransplant and continues in follow-up.

PMC5993360_02

Male

The second patient was a 65-year-old man who originally presented in December of 2014 with fevers, fatigue, thrombocytopenia, anemia, and leukocytosis. Peripheral blood smear revealed blasts with Auer rods, and bone marrow biopsy demonstrated acute promyelocytic leukemia with t(15;17) present. His disease was characterized as high-risk given a white blood cell count of 56.1 x 103/uL. The patient initially received ATRA 45 mg/m2/day and ATO 0.15 mg/kg daily but developed symptomatic QT prolongation and proceeded to treatment with idarubicin. His course was complicated by prolonged neutropenia with Pseudomonas bacteremia and Aspergillus pneumonia requiring filgrastim and granulocyte transfusions. Bone marrow biopsy following induction was negative for blast cells with normal molecular pathology and negative FISH testing for the t(15;17) translocation. He received three cycles of consolidation consisting of ATRA with idarubicin, mitoxantrone, and cytarabine followed by maintenance therapy with methotrexate 15 mg weekly, 6-mercaptopurine (6-MP) 50 mg daily, and intermittent ATRA 50 mg bid. One year into maintenance, the patient developed pancytopenia, and methotrexate and 6-MP were stopped. A short time later, he developed intermittent right facial paresthesia. MRI brain was concerning for hypointensity over the cerebellum, reflective of subarachnoid bleeding, and hyperintensity in some regions. Lumbar puncture revealed 78% promyelocytes with cytogenetics from cerebrospinal fluid positive for t(15;17). Bone marrow biopsy showed no evidence of blasts, but the karyotype disclosed a new set of anomalies with monosomy of chromosome 7 and an extra marker chromosome in 18 of 20 cells observed (+mar(18)). There were no marrow cells with t(15;17) by FISH or routine karyotype. Hematologic malignancy sequencing panel noted two mutations in the SET binding protein 1 (SETBP1) with allele frequency 36% and 12%. The patient was treated with intrathecal methotrexate 12 mg and intrathecal cytarabine 100 mg followed by whole brain radiation, 2 Gy x 9 fractions. Repeat bone marrow biopsy one month later revealed no excess blasts by flow cytometry, but the karyotype showed persistent monosomy 7 and an extra marker chromosome in all 20 cells observed (+mar(20)). The patient received systemic chemotherapy consisting of cytarabine 100 mg/m2 x 7 days and daunorubicin 60 mg/m2 followed by allogeneic hematopoietic stem cell transplantation with reduced intensity conditioning of busulfan, fludarabine, and antithymocyte globulin (ATG). Post-bone marrow transplant bone marrow biopsy showed no evidence of disease and full donor chimerism. Repeat MRI brain/orbits showed resolution of previously seen enhancement. The patient is doing well 10 months post-bone marrow transplant.

6-mp, 6-mercaptopurine, aml, acute myelocytic leukemia, apl, acute promyelocytic leukemia, atg, antithymyocyte globulin, ato, arsenic trioxide, atra, all-trans retinoic acid, acute myelocytic leukemia (aml), cr, complete remission, fish, fluorescence in situ hybridization, mds, myelodysplastic syndrome, myelodysplastic syndrome (mds), pml-raralpha, promyelocytic leukemia/retinoic acid receptor alpha, secondary clone, therapy-related acute myelocytic leukemia (t-aml), therapy-related myelodysplastic syndrome (t-mds), t- mds, therapy-related myelodysplastic syndrome, t-aml, therapy-related acute myelocytic leukemia

PMC7116975_01

Female

Both were Block E residents. The first case, Miss J, was a young university graduate. She previously worked in a private tuition center but was fired after the outbreak. Having lived in AG for 20 years, she was acquainted with many Block E residents who passed away or became infected during the outbreak. She and her family members were not infected, but were quarantined in an isolation camp in April 2003. Mrs. B, the second case, was a married woman with a 9-year-old daughter. She was one of the first batch of infected residents and experienced unpleasant treatment in hospital. She voluntarily quit her clerical job after falling ill. Because of unfair treatment in the workplace, her husband quit his job too. Her daughter was told to stop attending school owing to her status as a resident of AG.

PMC8531733_01

Male

The patient is a 67-year-old malewith lung lesions, who has been diagnosed with GPA since August 2019. A written informed consent was obtained from the patient.He presented early clinical symptoms including a mild fever (37.5 C), cough, and bloody sputum (hemoptysis). Following a computed tomography (CT) scan, a big pulmonary mass was observed in the right lung [Figure 1]. The patient also had high values of erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). Moreover, the negative results of tuberculosis (TB), interferon gamma release assay (IGRA), and acid-fast Bacillus tests and the positive results for the PR3-ANCA (cANCA) test (more than three times the normal value) led to the rejection of TB and the diagnosis of GPA. Therefore, as the induction therapy, the patient was immediately treated with 500 mg/day of rituximab (total cumulative dose = 2 g) and methylprednisolone 500 mg pulse (1 g/day) for 3 days. Moreover, the patient also took other medications including prednisolone (1.25 mg/day), cotrimoxazole 400/80 mg (400/80 mg/12 h), and iron-folic acid 1 mg (1 mg/day). After disappearing the early symptoms (remission phase), the patient was scheduled to receive rituximab (500 mg) every 6 months for six consecutive periods. The patient also suffered from cardiovascular disease before being diagnosed with GPA and used carvedilol 6.25 mg (6.25 mg/day), losartan 25 mg (1 tablet/day), and atorvastatin 20 mg (1 tablet/day) to treat it. Treatment with prednisolone (1.25 mg/day) continued until on April 4, 2020 when the patient visited the doctor for only brief symptoms of shortness of breath. According to the chest X-ray results [Figure 2], increasing the amounts of cANCA (145 U/mL), and CRP (58.9 mg/L), he was diagnosed with a pulmonary abscess due to GPA. Therefore, the dose of prednisolone increased up to 15 mg/day, and he was also prescribed hydroxychloroquine sulfate 200 mg (200 mg/day) and azithromycin 250 mg (500 mg [2 tablets] on the 1st day and 250 mg/day from the 2nd day to the 5th day), which quickly improved his clinical conditions. Two weeks later (April 20, 2020) that coincided with an increase in the prevalence of COVID-19, the patient went to a hospital with symptoms including body aches, a nonproductive cough, shortness of breath, sore throat, loss of appetite, nausea and vomiting, fatigue, and severe weakness. A reverse transcription (RT)-polymerase chain reaction (PCR) test and lung CT scan [Figure 3] were performed to check the possibility of COVID-19. The RT-PCR test was positive for COVID-19, and the result of the CT scan showed the signs of bilateral multiple ground-glass opacity that were indistinguishable from the recurrence of GPA. The patient was immediately hospitalized, and his vital signs including O2 Sat (87%), PR, (89) temperature (36.8 C), and blood pressure (BP) (137/98 mm Hg) were recorded. He was treated with hydroxychloroquine sulfate 200 mg (200 mg/6 h), azithromycin 500 mg (500 mg/8 h), prednisolone 5 mg TDS (5 mg/8 h), and cotrimoxazole 400/80 mg BD (400/80 mg/12 h), while he was receiving folic acid 1 mg (1 tablet/day), chlorphenamine 4 mg (1 tablet/day), carvedilol 6.25 mg (6.25 mg/day), losartan 25 mg (25 mg/day), atorvastatin 20 mg (20 mg/day). During his hospitalization, the COVID-19 symptoms were mild. A week later of the hospitalization, with the disappearance of the initial symptoms, a negative result of RT-PCR and appropriate vital signs including O2 Sat (92%), PR (79), temperature (36.5 C), and BP (100/6 mm Hg), the patient was allowed to leave the hospital and undergo the home quarantine. All treatments for COVID-19 were applied before the second period of rituximab infusions.

covid-19, cytokine storm, granulomatosis with polyangiitis, immunosuppressive drugs, rituximab

The results of computed tomography scan of the lung with granulomatosis with polyangiitis (a and b). There is a big pulmonary mass in the right lung indicated by arrows.

PMC8531733_01

Male

The patient is a 67-year-old malewith lung lesions, who has been diagnosed with GPA since August 2019. A written informed consent was obtained from the patient.He presented early clinical symptoms including a mild fever (37.5 C), cough, and bloody sputum (hemoptysis). Following a computed tomography (CT) scan, a big pulmonary mass was observed in the right lung [Figure 1]. The patient also had high values of erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). Moreover, the negative results of tuberculosis (TB), interferon gamma release assay (IGRA), and acid-fast Bacillus tests and the positive results for the PR3-ANCA (cANCA) test (more than three times the normal value) led to the rejection of TB and the diagnosis of GPA. Therefore, as the induction therapy, the patient was immediately treated with 500 mg/day of rituximab (total cumulative dose = 2 g) and methylprednisolone 500 mg pulse (1 g/day) for 3 days. Moreover, the patient also took other medications including prednisolone (1.25 mg/day), cotrimoxazole 400/80 mg (400/80 mg/12 h), and iron-folic acid 1 mg (1 mg/day). After disappearing the early symptoms (remission phase), the patient was scheduled to receive rituximab (500 mg) every 6 months for six consecutive periods. The patient also suffered from cardiovascular disease before being diagnosed with GPA and used carvedilol 6.25 mg (6.25 mg/day), losartan 25 mg (1 tablet/day), and atorvastatin 20 mg (1 tablet/day) to treat it. Treatment with prednisolone (1.25 mg/day) continued until on April 4, 2020 when the patient visited the doctor for only brief symptoms of shortness of breath. According to the chest X-ray results [Figure 2], increasing the amounts of cANCA (145 U/mL), and CRP (58.9 mg/L), he was diagnosed with a pulmonary abscess due to GPA. Therefore, the dose of prednisolone increased up to 15 mg/day, and he was also prescribed hydroxychloroquine sulfate 200 mg (200 mg/day) and azithromycin 250 mg (500 mg [2 tablets] on the 1st day and 250 mg/day from the 2nd day to the 5th day), which quickly improved his clinical conditions. Two weeks later (April 20, 2020) that coincided with an increase in the prevalence of COVID-19, the patient went to a hospital with symptoms including body aches, a nonproductive cough, shortness of breath, sore throat, loss of appetite, nausea and vomiting, fatigue, and severe weakness. A reverse transcription (RT)-polymerase chain reaction (PCR) test and lung CT scan [Figure 3] were performed to check the possibility of COVID-19. The RT-PCR test was positive for COVID-19, and the result of the CT scan showed the signs of bilateral multiple ground-glass opacity that were indistinguishable from the recurrence of GPA. The patient was immediately hospitalized, and his vital signs including O2 Sat (87%), PR, (89) temperature (36.8 C), and blood pressure (BP) (137/98 mm Hg) were recorded. He was treated with hydroxychloroquine sulfate 200 mg (200 mg/6 h), azithromycin 500 mg (500 mg/8 h), prednisolone 5 mg TDS (5 mg/8 h), and cotrimoxazole 400/80 mg BD (400/80 mg/12 h), while he was receiving folic acid 1 mg (1 tablet/day), chlorphenamine 4 mg (1 tablet/day), carvedilol 6.25 mg (6.25 mg/day), losartan 25 mg (25 mg/day), atorvastatin 20 mg (20 mg/day). During his hospitalization, the COVID-19 symptoms were mild. A week later of the hospitalization, with the disappearance of the initial symptoms, a negative result of RT-PCR and appropriate vital signs including O2 Sat (92%), PR (79), temperature (36.5 C), and BP (100/6 mm Hg), the patient was allowed to leave the hospital and undergo the home quarantine. All treatments for COVID-19 were applied before the second period of rituximab infusions.

covid-19, cytokine storm, granulomatosis with polyangiitis, immunosuppressive drugs, rituximab

The results of computed tomography scan of the lung with granulomatosis with polyangiitis (a and b). There is a big pulmonary mass in the right lung indicated by arrows.

PMC8531733_01

Male

The patient is a 67-year-old malewith lung lesions, who has been diagnosed with GPA since August 2019. A written informed consent was obtained from the patient.He presented early clinical symptoms including a mild fever (37.5 C), cough, and bloody sputum (hemoptysis). Following a computed tomography (CT) scan, a big pulmonary mass was observed in the right lung [Figure 1]. The patient also had high values of erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). Moreover, the negative results of tuberculosis (TB), interferon gamma release assay (IGRA), and acid-fast Bacillus tests and the positive results for the PR3-ANCA (cANCA) test (more than three times the normal value) led to the rejection of TB and the diagnosis of GPA. Therefore, as the induction therapy, the patient was immediately treated with 500 mg/day of rituximab (total cumulative dose = 2 g) and methylprednisolone 500 mg pulse (1 g/day) for 3 days. Moreover, the patient also took other medications including prednisolone (1.25 mg/day), cotrimoxazole 400/80 mg (400/80 mg/12 h), and iron-folic acid 1 mg (1 mg/day). After disappearing the early symptoms (remission phase), the patient was scheduled to receive rituximab (500 mg) every 6 months for six consecutive periods. The patient also suffered from cardiovascular disease before being diagnosed with GPA and used carvedilol 6.25 mg (6.25 mg/day), losartan 25 mg (1 tablet/day), and atorvastatin 20 mg (1 tablet/day) to treat it. Treatment with prednisolone (1.25 mg/day) continued until on April 4, 2020 when the patient visited the doctor for only brief symptoms of shortness of breath. According to the chest X-ray results [Figure 2], increasing the amounts of cANCA (145 U/mL), and CRP (58.9 mg/L), he was diagnosed with a pulmonary abscess due to GPA. Therefore, the dose of prednisolone increased up to 15 mg/day, and he was also prescribed hydroxychloroquine sulfate 200 mg (200 mg/day) and azithromycin 250 mg (500 mg [2 tablets] on the 1st day and 250 mg/day from the 2nd day to the 5th day), which quickly improved his clinical conditions. Two weeks later (April 20, 2020) that coincided with an increase in the prevalence of COVID-19, the patient went to a hospital with symptoms including body aches, a nonproductive cough, shortness of breath, sore throat, loss of appetite, nausea and vomiting, fatigue, and severe weakness. A reverse transcription (RT)-polymerase chain reaction (PCR) test and lung CT scan [Figure 3] were performed to check the possibility of COVID-19. The RT-PCR test was positive for COVID-19, and the result of the CT scan showed the signs of bilateral multiple ground-glass opacity that were indistinguishable from the recurrence of GPA. The patient was immediately hospitalized, and his vital signs including O2 Sat (87%), PR, (89) temperature (36.8 C), and blood pressure (BP) (137/98 mm Hg) were recorded. He was treated with hydroxychloroquine sulfate 200 mg (200 mg/6 h), azithromycin 500 mg (500 mg/8 h), prednisolone 5 mg TDS (5 mg/8 h), and cotrimoxazole 400/80 mg BD (400/80 mg/12 h), while he was receiving folic acid 1 mg (1 tablet/day), chlorphenamine 4 mg (1 tablet/day), carvedilol 6.25 mg (6.25 mg/day), losartan 25 mg (25 mg/day), atorvastatin 20 mg (20 mg/day). During his hospitalization, the COVID-19 symptoms were mild. A week later of the hospitalization, with the disappearance of the initial symptoms, a negative result of RT-PCR and appropriate vital signs including O2 Sat (92%), PR (79), temperature (36.5 C), and BP (100/6 mm Hg), the patient was allowed to leave the hospital and undergo the home quarantine. All treatments for COVID-19 were applied before the second period of rituximab infusions.

covid-19, cytokine storm, granulomatosis with polyangiitis, immunosuppressive drugs, rituximab

Computed tomography scan of the lung with COVID-19 (a-d). There are multiple scattered patchy ground-glass opacities in both lungs (short arrows), mostly with peripheral distribution, which are highly suggestive for COVID-19 pneumonia. There is also a cavity lesion (long arrows) in upper zone of right lung adjacent to major fissure, suggesting for concomitant infective or noninfective processes.

PMC8531733_01

Male

The patient is a 67-year-old malewith lung lesions, who has been diagnosed with GPA since August 2019. A written informed consent was obtained from the patient.He presented early clinical symptoms including a mild fever (37.5 C), cough, and bloody sputum (hemoptysis). Following a computed tomography (CT) scan, a big pulmonary mass was observed in the right lung [Figure 1]. The patient also had high values of erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). Moreover, the negative results of tuberculosis (TB), interferon gamma release assay (IGRA), and acid-fast Bacillus tests and the positive results for the PR3-ANCA (cANCA) test (more than three times the normal value) led to the rejection of TB and the diagnosis of GPA. Therefore, as the induction therapy, the patient was immediately treated with 500 mg/day of rituximab (total cumulative dose = 2 g) and methylprednisolone 500 mg pulse (1 g/day) for 3 days. Moreover, the patient also took other medications including prednisolone (1.25 mg/day), cotrimoxazole 400/80 mg (400/80 mg/12 h), and iron-folic acid 1 mg (1 mg/day). After disappearing the early symptoms (remission phase), the patient was scheduled to receive rituximab (500 mg) every 6 months for six consecutive periods. The patient also suffered from cardiovascular disease before being diagnosed with GPA and used carvedilol 6.25 mg (6.25 mg/day), losartan 25 mg (1 tablet/day), and atorvastatin 20 mg (1 tablet/day) to treat it. Treatment with prednisolone (1.25 mg/day) continued until on April 4, 2020 when the patient visited the doctor for only brief symptoms of shortness of breath. According to the chest X-ray results [Figure 2], increasing the amounts of cANCA (145 U/mL), and CRP (58.9 mg/L), he was diagnosed with a pulmonary abscess due to GPA. Therefore, the dose of prednisolone increased up to 15 mg/day, and he was also prescribed hydroxychloroquine sulfate 200 mg (200 mg/day) and azithromycin 250 mg (500 mg [2 tablets] on the 1st day and 250 mg/day from the 2nd day to the 5th day), which quickly improved his clinical conditions. Two weeks later (April 20, 2020) that coincided with an increase in the prevalence of COVID-19, the patient went to a hospital with symptoms including body aches, a nonproductive cough, shortness of breath, sore throat, loss of appetite, nausea and vomiting, fatigue, and severe weakness. A reverse transcription (RT)-polymerase chain reaction (PCR) test and lung CT scan [Figure 3] were performed to check the possibility of COVID-19. The RT-PCR test was positive for COVID-19, and the result of the CT scan showed the signs of bilateral multiple ground-glass opacity that were indistinguishable from the recurrence of GPA. The patient was immediately hospitalized, and his vital signs including O2 Sat (87%), PR, (89) temperature (36.8 C), and blood pressure (BP) (137/98 mm Hg) were recorded. He was treated with hydroxychloroquine sulfate 200 mg (200 mg/6 h), azithromycin 500 mg (500 mg/8 h), prednisolone 5 mg TDS (5 mg/8 h), and cotrimoxazole 400/80 mg BD (400/80 mg/12 h), while he was receiving folic acid 1 mg (1 tablet/day), chlorphenamine 4 mg (1 tablet/day), carvedilol 6.25 mg (6.25 mg/day), losartan 25 mg (25 mg/day), atorvastatin 20 mg (20 mg/day). During his hospitalization, the COVID-19 symptoms were mild. A week later of the hospitalization, with the disappearance of the initial symptoms, a negative result of RT-PCR and appropriate vital signs including O2 Sat (92%), PR (79), temperature (36.5 C), and BP (100/6 mm Hg), the patient was allowed to leave the hospital and undergo the home quarantine. All treatments for COVID-19 were applied before the second period of rituximab infusions.

covid-19, cytokine storm, granulomatosis with polyangiitis, immunosuppressive drugs, rituximab

Computed tomography scan of the lung with COVID-19 (a-d). There are multiple scattered patchy ground-glass opacities in both lungs (short arrows), mostly with peripheral distribution, which are highly suggestive for COVID-19 pneumonia. There is also a cavity lesion (long arrows) in upper zone of right lung adjacent to major fissure, suggesting for concomitant infective or noninfective processes.

PMC8531733_01

Male

The patient is a 67-year-old malewith lung lesions, who has been diagnosed with GPA since August 2019. A written informed consent was obtained from the patient.He presented early clinical symptoms including a mild fever (37.5 C), cough, and bloody sputum (hemoptysis). Following a computed tomography (CT) scan, a big pulmonary mass was observed in the right lung [Figure 1]. The patient also had high values of erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). Moreover, the negative results of tuberculosis (TB), interferon gamma release assay (IGRA), and acid-fast Bacillus tests and the positive results for the PR3-ANCA (cANCA) test (more than three times the normal value) led to the rejection of TB and the diagnosis of GPA. Therefore, as the induction therapy, the patient was immediately treated with 500 mg/day of rituximab (total cumulative dose = 2 g) and methylprednisolone 500 mg pulse (1 g/day) for 3 days. Moreover, the patient also took other medications including prednisolone (1.25 mg/day), cotrimoxazole 400/80 mg (400/80 mg/12 h), and iron-folic acid 1 mg (1 mg/day). After disappearing the early symptoms (remission phase), the patient was scheduled to receive rituximab (500 mg) every 6 months for six consecutive periods. The patient also suffered from cardiovascular disease before being diagnosed with GPA and used carvedilol 6.25 mg (6.25 mg/day), losartan 25 mg (1 tablet/day), and atorvastatin 20 mg (1 tablet/day) to treat it. Treatment with prednisolone (1.25 mg/day) continued until on April 4, 2020 when the patient visited the doctor for only brief symptoms of shortness of breath. According to the chest X-ray results [Figure 2], increasing the amounts of cANCA (145 U/mL), and CRP (58.9 mg/L), he was diagnosed with a pulmonary abscess due to GPA. Therefore, the dose of prednisolone increased up to 15 mg/day, and he was also prescribed hydroxychloroquine sulfate 200 mg (200 mg/day) and azithromycin 250 mg (500 mg [2 tablets] on the 1st day and 250 mg/day from the 2nd day to the 5th day), which quickly improved his clinical conditions. Two weeks later (April 20, 2020) that coincided with an increase in the prevalence of COVID-19, the patient went to a hospital with symptoms including body aches, a nonproductive cough, shortness of breath, sore throat, loss of appetite, nausea and vomiting, fatigue, and severe weakness. A reverse transcription (RT)-polymerase chain reaction (PCR) test and lung CT scan [Figure 3] were performed to check the possibility of COVID-19. The RT-PCR test was positive for COVID-19, and the result of the CT scan showed the signs of bilateral multiple ground-glass opacity that were indistinguishable from the recurrence of GPA. The patient was immediately hospitalized, and his vital signs including O2 Sat (87%), PR, (89) temperature (36.8 C), and blood pressure (BP) (137/98 mm Hg) were recorded. He was treated with hydroxychloroquine sulfate 200 mg (200 mg/6 h), azithromycin 500 mg (500 mg/8 h), prednisolone 5 mg TDS (5 mg/8 h), and cotrimoxazole 400/80 mg BD (400/80 mg/12 h), while he was receiving folic acid 1 mg (1 tablet/day), chlorphenamine 4 mg (1 tablet/day), carvedilol 6.25 mg (6.25 mg/day), losartan 25 mg (25 mg/day), atorvastatin 20 mg (20 mg/day). During his hospitalization, the COVID-19 symptoms were mild. A week later of the hospitalization, with the disappearance of the initial symptoms, a negative result of RT-PCR and appropriate vital signs including O2 Sat (92%), PR (79), temperature (36.5 C), and BP (100/6 mm Hg), the patient was allowed to leave the hospital and undergo the home quarantine. All treatments for COVID-19 were applied before the second period of rituximab infusions.

covid-19, cytokine storm, granulomatosis with polyangiitis, immunosuppressive drugs, rituximab

Computed tomography scan of the lung with COVID-19 (a-d). There are multiple scattered patchy ground-glass opacities in both lungs (short arrows), mostly with peripheral distribution, which are highly suggestive for COVID-19 pneumonia. There is also a cavity lesion (long arrows) in upper zone of right lung adjacent to major fissure, suggesting for concomitant infective or noninfective processes.

PMC8531733_01

Male

The patient is a 67-year-old malewith lung lesions, who has been diagnosed with GPA since August 2019. A written informed consent was obtained from the patient.He presented early clinical symptoms including a mild fever (37.5 C), cough, and bloody sputum (hemoptysis). Following a computed tomography (CT) scan, a big pulmonary mass was observed in the right lung [Figure 1]. The patient also had high values of erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). Moreover, the negative results of tuberculosis (TB), interferon gamma release assay (IGRA), and acid-fast Bacillus tests and the positive results for the PR3-ANCA (cANCA) test (more than three times the normal value) led to the rejection of TB and the diagnosis of GPA. Therefore, as the induction therapy, the patient was immediately treated with 500 mg/day of rituximab (total cumulative dose = 2 g) and methylprednisolone 500 mg pulse (1 g/day) for 3 days. Moreover, the patient also took other medications including prednisolone (1.25 mg/day), cotrimoxazole 400/80 mg (400/80 mg/12 h), and iron-folic acid 1 mg (1 mg/day). After disappearing the early symptoms (remission phase), the patient was scheduled to receive rituximab (500 mg) every 6 months for six consecutive periods. The patient also suffered from cardiovascular disease before being diagnosed with GPA and used carvedilol 6.25 mg (6.25 mg/day), losartan 25 mg (1 tablet/day), and atorvastatin 20 mg (1 tablet/day) to treat it. Treatment with prednisolone (1.25 mg/day) continued until on April 4, 2020 when the patient visited the doctor for only brief symptoms of shortness of breath. According to the chest X-ray results [Figure 2], increasing the amounts of cANCA (145 U/mL), and CRP (58.9 mg/L), he was diagnosed with a pulmonary abscess due to GPA. Therefore, the dose of prednisolone increased up to 15 mg/day, and he was also prescribed hydroxychloroquine sulfate 200 mg (200 mg/day) and azithromycin 250 mg (500 mg [2 tablets] on the 1st day and 250 mg/day from the 2nd day to the 5th day), which quickly improved his clinical conditions. Two weeks later (April 20, 2020) that coincided with an increase in the prevalence of COVID-19, the patient went to a hospital with symptoms including body aches, a nonproductive cough, shortness of breath, sore throat, loss of appetite, nausea and vomiting, fatigue, and severe weakness. A reverse transcription (RT)-polymerase chain reaction (PCR) test and lung CT scan [Figure 3] were performed to check the possibility of COVID-19. The RT-PCR test was positive for COVID-19, and the result of the CT scan showed the signs of bilateral multiple ground-glass opacity that were indistinguishable from the recurrence of GPA. The patient was immediately hospitalized, and his vital signs including O2 Sat (87%), PR, (89) temperature (36.8 C), and blood pressure (BP) (137/98 mm Hg) were recorded. He was treated with hydroxychloroquine sulfate 200 mg (200 mg/6 h), azithromycin 500 mg (500 mg/8 h), prednisolone 5 mg TDS (5 mg/8 h), and cotrimoxazole 400/80 mg BD (400/80 mg/12 h), while he was receiving folic acid 1 mg (1 tablet/day), chlorphenamine 4 mg (1 tablet/day), carvedilol 6.25 mg (6.25 mg/day), losartan 25 mg (25 mg/day), atorvastatin 20 mg (20 mg/day). During his hospitalization, the COVID-19 symptoms were mild. A week later of the hospitalization, with the disappearance of the initial symptoms, a negative result of RT-PCR and appropriate vital signs including O2 Sat (92%), PR (79), temperature (36.5 C), and BP (100/6 mm Hg), the patient was allowed to leave the hospital and undergo the home quarantine. All treatments for COVID-19 were applied before the second period of rituximab infusions.

covid-19, cytokine storm, granulomatosis with polyangiitis, immunosuppressive drugs, rituximab

Computed tomography scan of the lung with COVID-19 (a-d). There are multiple scattered patchy ground-glass opacities in both lungs (short arrows), mostly with peripheral distribution, which are highly suggestive for COVID-19 pneumonia. There is also a cavity lesion (long arrows) in upper zone of right lung adjacent to major fissure, suggesting for concomitant infective or noninfective processes.

PMC8175160_01

Female

M is a 22-year-old woman with a history of EUPD. She has been known to child and adolescent mental health services (CAMHS) since the age of 14 with multiple characteristics of EUPD including impulsivity, lack of consideration of consequences of her actions, unpredictable and capricious mood, outbursts of emotion, incapacity to control behavioural explosions, quarrelsome behaviour and conflict with others, poor self-esteem, unstable interpersonal relationships, self-destructive behaviour, and suicide attempts. Her presentation to secondary mental health services was precipitated by sexual abuse by her brother when aged 10 and subsequent bullying at school due to her weight. She typically presented to the ED with extensive self-harm and suicidal intentions triggered by auditory hallucinations involving the voice of her brother. She was a psychiatric inpatient between 2011 and 2016 and responded well to a combination of clozapine and levomepromazine. She was subsequently discharged to supported accommodation. She had 14 admissions to the local acute psychiatric unit in the calendar year before the admission discussed here. The factors influencing her presentations were considered to be multifactorial, including being the victim of a sexual assault in May 2018 and nonconcordance with medication. In September 2018, she was brought to the ED by police under section 136 of the UK Mental Health Act with self-harm wounds and disclosing to police officers her intention to walk to a nearby motorway to commit suicide. She was extremely agitated, handcuffed to the bed trolley, and restrained for prolonged periods by four police officers and two members of the hospital security team. The police stayed in the hospital with her for nine hours, and subsequent restraint was carried out by six security staff. Staff support and various forms of sedation were used during the initial hours in ED to try and reduce her agitation and step-down restraint. Her medication on admission was clozapine 250 mg/day, paliperidone depot 75 mg/month, sertraline 150 mg/day, pirenzepine 50 mg/day, omeprazole 20 mg/day, atenolol 50 mg/day, ferrous fumarate 420 mg/day, desogestrel 75 micrograms/day, and an etonogestrel contraceptive implant. She had deep lacerations on her left arm and both legs, 12-14 cm in length, exposing subcutaneous fat. Surgical review concluded that the injuries required exploration and closure under general anaesthesia, but that the wounds did not pose a risk to life or limb, nor did they require emergency surgery or admission to a surgical bed. As she was detained under section 136 of the MHA (Mental Health Act) and there was no readily available alternative place of safety, she was admitted to facilitate a psychiatric assessment. She consistently refused treatment and was threatening to complete suicide on a local dual carriageway; twice earlier that year she had been removed from walking along the carriageway of the same road. A Mental Health Act (MHA) assessment took place 18 hours following admission. M was detained under section 3 of the MHA. She was scheduled for surgery to repair her self-harm wounds. She remained suicidal and continued trying to remove her lines and dressings. This was the start of a 128-day admission to the acute hospital where several life-threatening iatrogenic complications arose (Table 1). M was restrained at least 17 times, and intramuscular (IM) medication was used in nine of these incidents. She was intubated and transferred to the intensive care unit (ICU) four times to manage her behaviour. Various members of both the medical and liaison psychiatry (LP) teams involved determined on at least a daily basis that she did not have capacity to make decisions about her medical care and treatment. This opinion did not alter throughout her medical admission. M was finally transferred to Springbank ward, a specialist personality disorder unit in Fulbourn Hospital, on the morning of her 128th day of admission. At the point of transfer to Springbank, the liaison psychiatry and medical teams considered her mental state to be similar in terms of distress, attempts to self-harm (in frequency and severity) and statements of intended suicide as those throughout her acute hospital admission, including her first presentation to the ED. At the point of discharge, she was in ICU on 2 : 1 special observations. Her mobility was limited to 80 yards with a Zimmer frame and two members of staff assisting her. She required rapid access to the toilet because of urinary and faecal urgency. She had difficulties speaking or lying flat. Her leg wounds required ongoing dressings, and she required outpatient follow-up by cardiologists, ENT surgeons, and respiratory physicians. Springbank ward is the only specialist personality disorder unit in the NHS that accepts patients detained under a section of the MHA. It offers a one-year treatment pathway for women with a personality disorder who have not benefited from acute and community services or who are still considered to be at high risk of completed suicide. The use of the MHA is avoided, and detained patients are expected to set a discharge date from their detention early on in their admission. M was discharged from section 3 MHA after 18 days at Springbank. She was redetained under section 3 MHA on day 238 of her admission, due to a suspected psychotic episode when she was threatening to jump in front of traffic. The detention was followed by a series of severe self-harm incidents. The detention was rescinded after two days when it was established that her behaviour was not secondary to psychosis, but part of her personality disorder. When given the option of leaving the ward, she opted to stay, and her self-harm stopped. There were 26 significant incidents during her 372-day admission to Springbank (Table 2). The severity of the incidents on the ward was of equal or greater severity than those at first presentation to the ED. She frequently refused any interventions. The general approach adopted was to ask her to stop the self-harming behaviour, ask her to remove any inserted foreign bodies (or offer help in doing so), and ask her whether she wanted any treatment. Her wounds would typically require suturing, but she would often refuse this and refuse to go to the ED. Control over and responsibility for her treatment was given to her. She was never restrained and rapid tranquillisation was never given. She was never physically violent towards staff. The complications arising from not enforcing treatment (usually skin infections and large scars) were minimal in comparison to those that had arisen at the acute hospital and the general psychiatric ward (Table 1). Medication was not enforced. She was discharged into supported accommodation after completing the one-year treatment programme. Eight structured outcome measures were used to monitor her progress at Springbank. M showed improvement in nearly all outcome measures (discharge versus admission; supplementary data Table 3). On discharge, her regular medication included olanzapine depot 405 mg/fortnight, lithium carbonate 1000 mg nocte, prazosin 3 mg nocte, levomepromazine 50 mg tds, promethazine 50 mg tds, pregabalin 300 mg bd, levothyroxine 100 mcg od. Pro re nata (PRN) medications included levomepromazine 50-100 mg every 4 hours, diazepam 5 mg (up to 40 mg/day), salbutamol, Peptac, and codeine phosphate 30-60 mg qds. At the time of writing (September 2020), M has been discharged for 248 days. She has not had any further hospital admissions. Supplementary data Table 4 summarises her service use before and after her admission to Springbank. She is currently living in supported accommodation, engaging in voluntary work, and has been self-harm-free for over one year.

PMC9826549_01

Male

A 23-year-old healthy male division one football player felt a pop in his neck while weightlifting. Initial symptoms were left arm pain, radiculopathy, and global weakness. X-rays were negative for fracture or dislocation (Fig. 1, 2). His left arm pain and radiculopathy resolved with 2 weeks of rest, but, thereafter, he continued to have subjective weakness in his triceps. His main complaint was the loss push off strength with his dumb bell bench press. He could bench 110lbs on the right arm compared to only 65lbs with his left arm. At the 2-week mark post-injury, on physical examination, he had normal strength, sensation, and reflexes throughout the left upper extremity. The only positive finding was he had triceps muscle wasting. After 6 weeks post-injury and completion of physical therapy, stretching, and NSAID's, a MRI was obtained. This showed a left paracentral C6-C7 disk herniation extending into the foramen, causing foraminal stenosis and his symptoms (Fig. 3, 4). Due to significant muscle wasting and continued weakness after a course of conservative management, a C6-C7 anterior discectomy and arthroplasty were performed by a fellowship trained spine surgeon (Fig. 5, 6, 7, 8). In the post-operative setting, he underwent 4 weeks of rest. At the 4-week mark, he gradually increased his lifting and started performing running and agility drills with the team. At 8 weeks, he was cleared to return to sport. He is currently 9 months out from surgery and competing in contact sports without any complications.

cervical disk replacement, anterior cervical disk fusion, contact sports

PMC7282614_01

Female

Mrs. JR a 50-year-old woman, never treated for tuberculosis and no notion of smoking, but has been diabetic for 5 years. The patient reported for 9 months, a persistent cough with mucous expectoration and very abundant bronchorrhea (1000ml/day) (Figure 1) and stage III of mMRCdyspnea, in a context of apyrexia and deterioration of the general state. Clinical examination revealed a bilateral crackling rale, more marked on the left. The posteroanterior chest roentgenogram showed a heterogeneous opacity occupying the lower half of the left thoracic hemichamps associated with heterogeneous nodular opacities confluent on the right (Figure 2). The thoracic computed tomography (CT) showed an alveolar condensation of the left lower lobe containing an air bronchogram, associated with multiple nodular lesions and alveolar condensation of the right lung (Figure 3). Bronchial fibroscopy not supported by the patient due to abundant bronchorrhea. Transthoracic biopsy of the alveolar condensation was performed (guided by CT) by using the biopsy needle Gelman type (18 G 11 cm). It is concluded from invasive mucinous lepidic adenocarcinoma (Figure 4). The extension assessment did not show extrathoracic localization. After the confirmation of the diagnosis, the patient was referred to the oncology center for chemotherapy.

lung adenocarcinoma, alveolar opacity, pathology

The thoracic computed tomography (CT) showing an alveolar condensation of the left lower lobe containing an air bronchogram, associated with multiple nodular lesions and alveolar condensation of the right lung.

PMC4110384_01

Female

A 43-year-old female patient without evident disease previously presented to our hospital with a 4-month history of intermittent wandering arthralgia on the left side, and also with spiking fever (the highest body temperature up to 40 C), thoracalgia and sputum for 3 months. According to the examinations of the local hospital, computerized tomography (CT) scan of the chest showed bilateral pleural effusions leading to oppressive lung parenchyma; mild inflammatory infiltration of both lungs; slightly pericardial effusion; cardiomegaly and swelling lymph nodes on the right cardiodiaphragmatic angle. Distinctive laboratory findings, as shown in Table 1, easily played a role in establishing the following diagnoses: secondary pulmonary tuberculosis; tuberculous pleuritis; tuberculous pericarditis and hyperthyroidism. Therefore, the antituberculous chemotherapy and anti-thyroid drug (methimazole) were initiated; however, a poor response was obtained. Then the patient transferred to our rheumatology ward. On physical examination, she appeared irritable, general fatigue and underweight. And palpable lymph nodes at bilateral inguinal region and supraclavicular fossa were also found. Laboratory test are shown in Table 1. According to the laboratorical results of the local and our hospital, Graves' disease (GD) was diagnosed. Contrast-CT scan showed infection of bilateral lungs, slightly pericardial effusion and swelling lymph nodes at bilateral inguinal region and supraclavicular fossa. An abdominal ultrasound revealed splenomegaly. Thyroid ultrasonography revealed heterogeneous in echoic distribution and rich blood perfusion. Electrocardiogram showed only sinus tachycardia. A bone marrow biopsy and cytologic examination disclosed a hypercellular marrow hinting no lymphoma or other malignancies. Axillary lymph node biopsy displayed no lymphoma. According to the laboratory results, imaging studies, necessary exclusion and Yamaguchi et al. criteria, this case fulfilled the 1, 2 and 4 items of major criteria and 2 and 4 items of minor criteria, are shown in Table 2. AOSD was therefore diagnosed. Since hospitalization in our ward, the patient had undergone an intermittent spiking fever (range from 38 C to 40.1 C) with evanescent rash. Considering the side effect of fever induced by antituberculous drugs, so stopped the treatment. According to the thyroid hormone level mentioned above, the thyroid function was improved and temporarily anti-thyroid drugs did not appear to be used by us. Although antifebrile drugs such as antondin and radix bupleuri (a traditional medicine that enable treat fever) were injected, and temperature was kept high. But when methylprednisone 30 mg per day was initiated, fever and rash gradually disappeared as well as thoracalgia. After she had received 2 weeks of therapy, the dose of prednisone tapered slowly. The secondary thyroid hormone test indicated remarkable hyperthyroidism (significantly increased FT3, FT4 and decreased TSH). Hence, methimazole was added. A week later, she was discharged with normal thyroid hormone and improved symptoms. CT re-examination demonstrated the disappearance of inflammation. During 1-year follow-up, the both diseases activity remained in remission.

adult-onset still’s disease, autoimmune thyroid disease

PMC8627308_01

Female

A 52-year-old female patient, a never smoker, was initially diagnosed with advanced-stage lung adenocarcinoma (cT1bN3M0, stage IIIB). Wild-type epidermal growth factor receptor (EGFR mutation), anaplastic lymphoma kinase (ALK) rearrangement, ROS 1 rearrangement, BRAF V600E mutation, and MET exon 14 skipping mutation were detected via accompanying diagnostic tests. Based on the assessment using transbronchial lung biopsy (TBB) samples, the programmed death-ligand 1 expression was <1%. She received concurrent chemoradiation (60 Gy/30 Fr with cisplatin plus S-1), and four systemic treatments including immune check point inhibitor (carboplatin plus paclitaxel plus bevacizumab plus atezolizumab, docetaxel plus ramucirumab, pemetrexed, and nanoparticle albumin-bound paclitaxel) for each relapse at recurrence. However, rapid disease recurrence was observed with the progression of left lower lobe primary tumor, miliary lung metastasis, bilateral malignant pleural effusion, and appearance of carcinomatous lymphangitis on computed tomography (CT) scan (Figure 1). The serum carcinoembryonic antigen (CEA) level increased to 14,333.9 ng/mL. The patient's medical condition was affected as she presented with hypoxia, which required oxygen therapy via nasal cannula at a flow of 4 L per min, cancer pain, and cachexia, which needed opioid treatment. Her Eastern Cooperative Oncology Group PS score was assessed 3. TBB was again conducted for cancer genomic analysis using FoundationOne CDx as next-generation sequencing and HER2 exon 20 insertion mutation (M774-775ins) and HER2 amplification was detected. Immunohistochemical staining of TBB specimens, which was performed by a pathologist, revealed HER2 positivity (Figure 2). T-DXd was not approved for the treatment for NSCLC harboring HER2 mutation at that time in Japan. However, the patient's condition was serious, and T-DXd had a promising therapeutic effect against NSCLC harboring HER2 insertion mutation. Therefore, treatment with T-DXd, which was covered using the patient's own expense, was considered. After our cautious explanation about the risks and benefits of the drug was to the patient and her family, their informed consent was obtained. Treatment was started after the use of T-DXd was approved by Ethics Committee Review Board of Nippon Medical School Hospital (approval no. B-2020-297). Although participants received 6.4mg/kg in DISTNY Lung 01 trial, we conducted dose modification to 5.4 mg/kg of T-DXd for avoiding severe adverse event, considering her poor PS. CT scan performed 11 days after the administration of T-DXd presented that the size of the primary tumor decreased. Moreover, lung metastasis and pleural effusion improved (Figure 1). After 13 days the initiation of T-DXd, the need for oxygen administration was eliminated and the patient's PS improved from 3 to 1. After 23 days, she was discharged without O2 administration, and T-DXd treatment was continued in the outpatient department. The serum CEA level significantly decreased to 873 ng/mL with the treatment. The patient experienced adverse events (AEs) such as grade 2 neutropenia and grade 2 nausea, which were correlated with T-DXd treatment. After adjusting for treatment schedule, the patient tolerated the AEs. The durable response of T-DXd was observed between 6 months follow-up terms from initiation of T-DXd and her response was evaluated partial response using the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. The treatment is still ongoing, and severe AEs including interstitial lung disease (ILD) have not been observed.

her2 exon 20 insertion mutation, lung cancer, poor ps, trastuzumab deruxtecan

PMC3549891_02

Male

A 38-year-old Iranian man presented with a nine-month history of cerebellar ataxia and dysarthria, weight loss, and vomiting. Brain MRI showed cerebellar atrophy. CSF analysis showed CSF-restricted oligoclonal bands and 5 cells/mul. No further clinical data were available from this patient retrospectively. IHC was performed on cryosections of adult rhesus monkey, rat, and mouse cerebellum tissue (Euroimmun, Luebeck, Germany) as previously described. Briefly, sections were pretreated with formalin and 1% 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate (CHAPS) in PBS, blocked with 10% goat serum and then incubated with patient serum for 1 h. Binding of human immunoglobulin (Ig)G, IgA, and IgM to CNS tissue was detected by using polyclonal goat anti-human IgG antibodies conjugated to fluorescein isothiocyanate (FITC) (Euroimmun) or Alexa Fluor (AF) 568 (Invitrogen, Karlsruhe, Germany), and polyclonal goat anti-human IgM and anti-human IgA antibodies conjugated to FITC (Euroimmun), respectively. Sections were then mounted using glycerol standard immunofluorescence mounting medium containing 4',6-diamidino-2-phenylindole (DAPI) (1:1000) (Euroimmun) or ProLong Gold antifade reagent (Invitrogen). Slides were analyzed on a Nikon 90i upright fluorescence microscope and a Nikon A1 confocal microscope (Nikon Imaging Center, University of Heidelberg, Heidelberg, Germany). To evaluate IgG subclasses, serum and CSF samples were tested by IHC on mouse cerebellum sections as described above, with the following modifications: sections were blocked with 10% donkey serum; nonconjugated sheep anti-human IgG antibodies specific for IgG subclasses 1 to 4 (Binding site, Germany) were substituted for the FITC-labeled goat anti-human IgG antibody; and AF568-labeled donkey anti-sheep IgG (Invitrogen; absorbed against human IgG) was used to detect the subclass-specific antibodies. To confirm ARHGAP26 specificity, sera were preadsorbed overnight with human full-length ARHGAP26 (Biozol, Eching, Germany) and supernatants were tested by IHC as described above. Protran BA79 nitrocellulose membranes (0.1 mum) (Whatman, Fisher Scientific, Schwerte, Germany) were spotted with a 0.14 mug/mul solution of human full-length ARHGAP26 (10 mul/spot; Biozol). After drying, membranes were blocked with 5% bovine serum albumin (BSA) in Tris-buffered saline (TBS) for 1 h at room temperature (RT), washed three times in TBS with 0.05% Tween (TBS-T), and then incubated with a 1:20 dilution of the patient's serum in 0.1% BSA/TBS-T for 1 h at RT. A donkey anti-human IgG antibody labeled with IRdye 700DX (Rockland, Gilbertsville, PA, USA) was used to detect bound IgG. Stripes were finally washed in TBS and analyzed using an Odyssey fluorescence scanner (Licor, Lincoln, NE, USA) and Odyssey 2.0.40 application software (Licor). All samples were tested for anti-Hu, -Yo, -Ri, -CV2/CMRP5, -Ma/Ta, -Tr, -amphiphysin, -aquaporin-4, -GAD, -MAG, and -myelin antibodies by IHC on mouse, rat, and monkey brain and peripheral nerve tissue sections (Euroimmun, Luebeck, Germany), for anti-Hu, -Yo, -Ri, -CV2/CMRP5, -Ma/Ta, and -amphiphysin antibodies by using a commercially available line blot assay (Euroimmun, Germany), and for anti-NMDA-type glutamate receptor, anti-AMPA-type glutamate receptor, anti-GABA-B receptor, anti-CASPR2, anti-LGI1, anti-AQP4, and anti-glycine receptor antibodies using a panel of recombinant cell-based assays (Euroimmun, Germany).

PMC10244565_01

Male

A 27-year-old man with episodes of hemoptysis for the past 12 h and left-sided chest dull pain without apparent cause for 2 months was referred to the emergency department. The amount of hemoptysis was approximately 200 ml, with no dizziness, tachycardia and hypotension. Initial physical examination revealed decreased breath sounds with crackles on the left side, and the chest pain was not related to breathing. Additionally, the patient had symptoms of hypoxemia and tachypnea, indicating a potential respiratory or cardiovascular condition. Troponin T and brain natriuretic peptide levels were elevated at 313.8 (reference range: 0-14 ng/L) and 506 (reference range: <88 ng/L) ng/L, respectively, while other laboratory parameters were within normal limits. The patient had no previous medical history of tuberculosis, bronchiectasis, or chest trauma, and denied any prior occurrence of Kawasaki disease or chronic inflammatory disorders. The patient initially sought medical attention at a local hospital where a CT scan was performed and was diagnosed with "pneumonia" 2 months ago. However, despite being discharged after a 9-day hospital stay, the patient continued to experience persistent chest pain symptoms. The patient was admitted for further investigation due to the unclear cause of hemoptysis and chest pain. Chest x-ray (Figure 1A) showed an enlarged left cardiac silhouette with a conspicuous bulge encroaching on the left upper-middle lung field. In addition, bronchoscopy (Figure 1B) detected fresh blood in the left upper lobe bronchus, however, the definitive bleeding source was not identified. Subsequently, thoracic MRI with a T1W1 sequence (Figure 1C) demonstrated that the heterogeneous mass was essentially caused by active bleeding, and the possible diagnosis of a mediastinal tumor was excluded. Meanwhile, coronary CT angiography (Figures 1D,E) revealed a giant suspicious left coronary artery aneurysm (37 mm x 23 mm) wrapped in a large mediastinal mass (103 mm x 75 mm), which extended to the left chest wall and infiltrated the lung lobe. Furthermore, coronary angiography (Figure 1F; Supplementary Video S1) confirmed a saccular CAA originating from the middle portion of the left anterior descending artery. Based on these findings, the potential cause of hemoptysis was considered to be CAA rupturing into the left pulmonary parenchyma. The next day, the patient underwent emergency surgery due to the concern of a potentially life-threatening massive bleeding or acute myocardial infarction caused by the complete rupture of the coronary artery aneurysm. Preoperative transesophageal echocardiography showed a pericardial mass with normal cardiac function. During the median sternotomy, the pericardium prominently protrudes to the left, thereby presenting an ill-defined margin with pleura. After the removal of the limited thrombi eroding the left pleura densely and adhering to the left upper lung, a large pseudoaneurysm arising from a ruptured left CAA was identified (Figure 2A; Supplementary Video S2). The aneurysmal sac was resected, and a saphenous vein graft was used to bypass the distal left anterior descending artery (Figure 2B). The patient recovered uneventfully with cessation of hemoptysis, and predischarge CTA 9 days after surgery showed the disappearance of the left CAA (Figure 2C).

cardiac surgery, case report, giant coronary artery aneurysm, hemoptysis, multimodality imaging

PMC7737469_01

Male

A 10-month-old boy was brought to our hospital with fever, watery stool, and poor vitality. He developed fever from the 1st day, water stool (15-20 times a day) from the 2nd day, and poor vitality from the 7th day of illness. Vomiting occurred twice only on the 2nd day. He was hospitalized on the 7th day due to persistent symptoms and poor oral intake and vitality. He was previously healthy, with no recent history of travel, contact with sick individuals, or exposure to pets. His body temperature was 40.8 C; pulse, 184 bpm (normal); blood pressure, 121/66 mmHg; and respiratory rate, 36 breathes/min with an oxygen saturation of 99% on room air. On physical examination, he was nonresponsive and had cervical lymphadenopathy, increased bowel sounds, and peripheral cold sensation. No other lymph node swelling, rash, or edema was observed (Figure 1). Initial laboratory results revealed elevated inflammatory markers (white blood cell (WBC) count, 15,750/muL; C-reactive protein (CRP), 16.83 mg/dL; and procalcitonin, 8.4 ng/mL) and hyponatremia (130 mmol/L). Cervical ultrasonography revealed mild reactive lymphadenopathy (Figure 2). Abdominal ultrasonography (Figure 3) and computed tomography (CT) (Figure 4) revealed pitting-like wall thickness of the entire colon and an enlarged appendix. Initially, estimating the pathogenic bacteria and infection route was difficult through interviews; therefore, a broad-spectrum antibiotic therapy was administered (ampicillin: ABPC, 200 mg/kg/day + ceftriaxone (CTRX), 100 mg/kg/day). On the same day, 2-3-min convulsions occurred with upturn of the eyeball and poor complexion. Convulsions were identified as systemic tonic, without left-right differences. Cranial CT revealed no abnormal findings such as cerebral edema or neoplastic lesions, and cerebrospinal fluid examination revealed normal leukocyte levels or hypoglycemia (cerebrospinal fluid (CSF): glucose level of 73 mg/dL as compared to simultaneous blood glucose level of 113 mg/dL, protein of 13 mg/dL, and cell count of 4 cells/muL with 58% cells being neutrophil). On day 9 of illness, symmetrical pale erythema without blisters and bulges were observed on the patient's face and trunk. Follow-up laboratory results on the same day were as follows: WBC, 13290/muL and CRP, 23.3 mg/dL. The blood culture on the 7th day of the illness (hospitalization date) was reported to be positive for Gram-negative rod and was identified as Y. pseudotuberculosis. On the next day, the guardian was reinterviewed, revealing that they had been using spring water from nearby valleys for domestic purposes. The spring water was boiled and then used to melt the formula (artificial milk). Antibiotics were changed to meropenem (MEPM, 120 mg/kg/day), and intravenous immunoglobulin (IVIG, 500 mg/kg/day) was administered for hypogammaglobulinemia (443 mg/dL). On day 10 of illness, the fever subsided. On day 11, antibiotics were changed to ABPC (200 mg/kg/day) based on the antibiotic sensitivity to Y. pseudotuberculosis. Intravenous albumin (10 g/dose/day) was also administered because of body weight gain and edema associated with hypoalbuminemia. These treatments gradually improved his watery stool, rashes, and cervical lymphadenopathy. Oral intake became possible on day 12 of illness, antibiotics were continuously infused until day 18, and he was discharged on day 19. During the hospitalization, no symptoms of acute renal failure were suspected. Finally, Y. pseudotuberculosis was detected from the stool culture and loop-mediated isothermal amplification (LAMP), and Y. pseudotuberculosis-derived mitogen (YPM) antibody was also increased, resulting in the diagnosis of enteritis and bacteremia due to Y. pseudotuberculosis. After discharge, he presented desquamation of both hands on the 30th day of illness. He has been under follow-up care without coronary artery lesions.

PMC7331566_01

Male

An 89 year-old male was admitted to the ICU on April 14, 2020. The patient had a history of chronic obstructive pulmonary disease (COPD) on nocturnal oxygen therapy and no known cardiac disease. He had been hospitalized since March 30 because of COPD exacerbation. During his hospitalization his condition improved, but on April 8 he developed new-onset fever with hypoxemia and bilateral lung infiltrates. Reverse transcription polymerase chain reaction (RT-PCR) of a nasopharyngeal swab was positive for SARS-CoV-2. He was treated with hydroxychloroquine and azithromycin but was intubated on April 14 because of worsening hypoxemia. On admission, he was sedated and mechanically ventilated with a tidal volume of 6.5 ml/kg of Predicted Body Weight at a rate of 20 breaths per minute and Positive End-Expiratory Pressure (PEEP) of 8cmH2O. Physical examination was unremarkable and he was hemodynamically stable. He had a PaO2/FiO2 of 110, respiratory system compliance 35 ml/cmH2O, airway resistance 18cmH2O/L/sec and intrinsic PEEP of 2cmH2O. Central venous pressure (CVP) was 12 mmHg and central venous oxygen saturation (ScvO2) was 76 %. Electrocardiography (ECG) showed incomplete RBBB (Fig. 1). Chest X-ray revealed signs of emphysema and bilateral infiltrates (Fig. 2). Abnormal laboratory tests included mild leukocytosis with low lymphocyte count (800/muL) and elevated C-reactive protein (24.77 mg/dL; RR < 0.5 mg/dL), ferritin (2279 ng/mL; RR 11-307 ng/mL), interleukin-6 (52 pg/mL; RR <5 pg/mL) and d-dimer levels (1.65 mug/mL; RR < 0.89 mug/mL). A panel of lower respiratory specimen was negative, including influenza A and B, respiratory syncytial virus, corona virus, metapneumovirus, parainfluenza virus, rhinovirus, Legionella pneumophila, Myocoplasma pneumoniae, Chlamydia pneumoniae and bacteria. Urinary antigen testing for Legionella pneumophila and Streptococcus pneumoniae was also negative. Twenty-four hours after admission the patient developed acute circulatory collapse non-responding to fluid resuscitation and high dose of vasopressors. His CVP was 18 mmHg and ScvO2 was 58 %, indicating cardiogenic or obstructive pathophysiology of shock. Differential diagnosis included myocardial infarction, acute myocarditis due to COVID-19, acute pulmonary embolism, aortic dissection, tension pneumothorax and cardiac tamponade. ECG showed new onset infero-lateral ST elevation (Fig. 3). High sensitive cardiac troponin I was 35 pg/mL (RR < 34 pg/mL). Bedside transthoracic echocardiography (TTE) revealed an anterior pericardial effusion with right ventricular diastolic collapse and mitral valve inflow variation of 30 %, while left ventricular systolic function was normal with LVEF of 60 % (Video 1). Other causes of shock were excluded by TTE. Echo-guided pericardiocentesis was immediately performed and 200 mL of serous fluid were aspirated with subsequent hemodynamic improvement (Video 2). Pericardial drainage was maintained in situ for 24 h and yielded a total of 240 mL of fluid. The pericardial fluid tested negative for Gram stain and acid-fast bacilli smear. No growth on bacterial and fungal cultures was reported. Molecular testing for Mycobacterium tuberculosis was negative as was RT-PCR for SARS-CoV-2. Fluid cytology yielded no malignant cells. Thyroid function tests were normal. Serologic tests for Coxsackievirus, Echovirus, hepatitis viruses, cytomegalovirus, human immunodeficiency virus and autoantibodies were also negative. Treatment with colchicine was started. Following fluid drainage the patient was rapidly weaned off vasopressors. Repeat echocardiograms showed no recurrence of pericardial effusion. However, on the sixth day he developed septic shock and multi-organ failure caused by multi-drug resistant Acinetobacter baumanii and died.

covid-19, cardiac tamponade, pericardial effusion, shock

PMC8532252_01

Female

A 45-year-old Caucasian female with insignificant past medical history was diagnosed with a cutaneous malignant melanoma of the right femoral region. The primary lesion was resected and histology demonstrated a superficial spreading melanoma of Breslow thickness 3.2 mm, with ulceration. She then underwent a wide resection of the primary lesion as well as right inguinal sentinel lymph node excision. Wide resection margins were negative, whereas the sentinel lymph node was infiltrated. As a result, the patient underwent right inguinal lymph node dissection, which identified lymph node metastases in 2 out of 7 lymph nodes. Clinical examination and computed tomography (CT) of the brain, chest, abdomen, and pelvis did not reveal findings suggestive of distant metastatic disease. The pathology stage by American Joint Committee on Cancer (AJCC) (7th edition) was pT3b, N2a, M0 (stage IIIB). In addition, molecular tumor analysis showed a BRAFV600E mutation. The patient was started on adjuvant treatment with dabrafenib at a dose of 150 mg, twice daily and trametinib at a dose of 2 mg, once daily. During the first three months of treatment, she experienced recurrent episodes of low-grade fever, accompanied by nodular panniculitis of both lower limbs, which resolved after temporary treatment interruption. Following this, the drugs were well tolerated, with no evidence of disease recurrence; the patient discontinued treatment after a total treatment duration of 12 months. At CT restaging upon discontinuation, multiple, enlarged mediastinal lymph nodes were identified without pulmonary parenchymal lesions. In contrast, in previous restaging CT scans performed every three months while on treatment, no such lesions were present. The patient underwent bronchoscopy and transbronchial biopsy of a mediastinal lymph node. Histology revealed the presence of noncaseating epithelioid granulomas, suggestive of a sarcoid-like reaction (Figure 1). Complete blood count and biochemistry were normal. Serum angiotensin-converting enzyme was also normal. A QuantiFERON-TB Gold assay was negative. The patient remained asymptomatic, did not receive treatment, and during a 3-month follow-up, a CT scan showed regression of mediastinal lymphadenopathy and no evidence of melanoma metastases.

braf inhibitor, melanoma, sarcoid-like reaction, sarcoidosis, targeted therapy

PMC8532252_02

Male

A 38-year-old Caucasian male was diagnosed with a stage IIIc (TX, N3, M1a) malignant melanoma. The patient had no known risk factors for melanoma. He was treated with interferon alpha in an adjuvant setting; however, three years later he experienced an episode of gastrointestinal bleeding. After an enterectomy, this proved to be due to metastatic melanoma in the jejunum. The lesions were found positive for the V600E mutation of the BRAF gene. A CT scan performed a month later revealed two enlarged mesenteric lymph nodes; the patient was started on vemurafenib at 960 mg, twice daily and cobimetinib at 60 mg, once daily, for 21 days, followed by 7 days off, in the context of a phase III, randomized, blinded clinical trial (ClinicialTrials.gov identifier: CO39262/IMspire 150). As per protocol, atezolizumab at 840 mg every two weeks was added to the regimen after the first 4 weeks of treatment with vemurafenib and cobimetinib. Four months after treatment initiation, the patient achieved a complete remission (CR). Fifteen months since treatment initiation, the patient experienced a gradual decline of his renal function, evidenced by a decrease of his estimated glomerular filtration rate (eGFR), along with subtle proteinuria (0.34 g/24h) with no arterial pressure changes. His serum creatinine level was 1.81 mg/dl (baseline value being 0.75 mg/dl) corresponding to an eGFR of 44 ml/min/1.73 m2. The patient's hemoglobin level also decreased to 10.2 g/dl from a baseline of 12.4 g/dl. No metabolic acidosis was found. His erythrocyte sedimentation rate was 65 mm/h, with no c-reactive protein increase. There was no increase in urine leukocytes and a urine culture was found negative. A kidney and renal arteries ultrasound revealed no findings, while a positron emission tomography (PET)-CT scan confirmed a sustained CR of his advanced melanoma. Treatment with vemurafenib and cobimetinib was temporarily withheld and his renal function improved; however, upon re-initiation of treatment, his eGFR declined once again (serum creatinine of 2.70 g/dl, eGFR 31 ml/min/1.73 m2) and the drugs were once more discontinued. Atezolizumab was also temporarily discontinued and a renal biopsy was performed. The histologic evaluation revealed the presence of non-necrotizing granulomas in the interstitial space (Figure 2), findings indicative of a granulomatous nephritis. In addition, a tuberculin skin test was negative, as was a urine culture for Mycobacterium tuberculosis. Vemurafenib and cobimetinib were permanently discontinued and the patient was started on methylprednisolone at 0.75 mg/kg/day for a week, with rapid tapering during the following month. After the first week of corticosteroids, the patient's eGFR normalized, while treatment with atezolizumab was resumed. Twenty-nine months after resuming treatment, the patient is still in CR under atezolizumab, without any renal function impairment.

braf inhibitor, melanoma, sarcoid-like reaction, sarcoidosis, targeted therapy

PMC8532252_03

Female

A 54-year-old Caucasian woman was diagnosed at the age of 48 with a BRAF-mutated, stage IIIc (T3b, N1a, M0) melanoma on her left calf. She was treated with interferon alpha in the adjuvant setting, but two years letter an in-transit lesion on her left thigh emerged and was excised. She was then treated with ipilimumab, but treatment was discontinued due to hypophysitis. A year later, she developed a subcutaneous nodule on her chest, the histologic examination of which was consistent with a metastasis. She was treated with nivolumab, at 240 mg every two weeks, but six months later she experienced a grade-3 increase of the liver enzymes [serum glutamic oxaloacetic transaminase (SGOT)/serum glutamic pyruvic transaminase (SGPT)] and nivolumab was permanently discontinued. She was then started with dabrafenib at 150 mg twice a day and trametinib at 2 mg once a day in the adjuvant setting. The patient experienced recurrent panniculitis lesions on both lower limbs and the abdominal wall during the first four months of treatment; nine months after treatment initiation, upon her 3rd imaging assessment of response, several enlarged paratracheal, subcarinal, aortopulmonary window, and hilar lymph nodes were found without any parenchymal lung lesions. No other signs of disease progression were found. The patient underwent a bronchoscopy and an endobronchial ultrasound-guided biopsy (EBUS-TBNA) of one of the subcarinal lymph nodes. The histologic evaluation of the lesions revealed epithelioid non-caseating granulomas without multinucleated giant cells, suggestive of a SLR. Her complete blood count, biochemistry profile, and serum angiotensin-converting enzyme (sACE) levels were within normal limits while an interferon gamma release assay (IGRA) was found to be negative. The patient received no treatment for these lesions and continued treatment with dabrafenib and trametinib without any dose reduction. Eight months later, she is still in complete remission, with no change in the number and/or size of the lymph nodes. Scarce erythema nodosum lesions still come up on her legs but are well-tolerated.

braf inhibitor, melanoma, sarcoid-like reaction, sarcoidosis, targeted therapy

PMC7361883_01

Female

A 54-year-old postmenopausal African American female, G4P3013, with a past medical history of type 2 diabetes mellitus, hypertension, hypothyroidism, and stage 5 chronic kidney disease with multiple hospitalizations for hypercalcemia as well as recurrent pleural effusions, with a history of omental carcinomatosis of unknown origin, was referred to the gynecology-oncology service at a local community hospital following a laparoscopic incarcerated hernia repair where multiple abdominal lesions suspicious of ovarian carcinomatosis were visualized. The lesions were noted throughout the abdomen including the abdominal wall, bowel, liver, and pelvis. Biopsies of the lesions taken from the omentum and abdominal wall were found to be granulomatous with chronic inflammation and multinucleated giant cells. Some granulomas were matted, and others showed foreign bodies containing crystalloid material and rare granulomatous necrosis. Periodic acid-Schiff stain and acid fast bacilli stain were negative. Although cytology did not suggest neoplasm, the patient was immediately referred to the gynecology-oncology clinic due to the suspicion of an ovarian neoplasm. On presentation to gynecology-oncology clinic, the patient offered no gynecological complaints but endorsed nonspecific symptoms. She complained of anorexia and accompanied weight loss. Hospital records confirmed a fifty-nine-pound weight loss over seven months. She also complained of a chronic cough with scant-sputum production. She denied abdominal pain, abdominal cramping, vaginal bleeding, abdominal bloating, nausea, vomiting, and constipation. On exam, the patient was noted to have abdominal ascites, and her CA-125 level was elevated at 57.4 U/ml, which had risen from 39.9 U/ml a month prior. Following the appointment, she was scheduled for a diagnostic laparoscopy with possible hysterectomy and bilateral salpingo-oophorectomy; however, surgery was delayed due to her being hospitalized for symptomatic hypercalcemia and recurrent pleural effusions. Once the patient was stabilized, she was taken to the operating room for diagnostic laparoscopy. Intra-abdominal survey revealed white tubercle-like lesions that were consistent with peritoneal tuberculosis. Laparoscopic scissors were used to excise a piece of the peritoneal wall containing the tubercle-like lesions. The tissue was then sent to pathology. The omental biopsy was originally reported as adipose tissue showing focal fibrosis, focal mild acute inflammation, few cyst formation, and multiple granulomatous chronic inflammation, with multinucleated giant cells. Periodic acid-Schiff stain and acid fast bacilli stain were negative, and a diagnosis of peritoneal tuberculosis was made. The patient was immediately started on rifampin, isoniazid, pyrazinamide, ethambutol (RIPE) therapy, supplemented with azithromycin and vitamin B6. After several weeks of RIPE therapy, the patient was not showing any signs or improvement. Adenosine deaminase level was tested in the patients' pleural fluid and found to be elevated at 28.7 U/l. She also had a quantiferon test performed which was indeterminate. Decision was made to have the pathology from the tissue sample taken during surgery reviewed. The pathology revealed nonnecrotizing granulomatous inflammation (Figures 1(a) and 1(b)) and multinucleated giant cells (Figures 2 and 3(b)) consistent with sarcoidosis. The patient was immediately referred to the department of pulmonology and rheumatology, at which point she was started on corticosteroids and had an improvement in her condition.

PMC2644317_01

Male

A 31-year-old white man from Caracas, Venezuela presented in the emergency room complaining of daily evening fever, night sweats, pleuritic chest pain and shortness of breath for the previous 2 weeks. Up until 2-weeks before, over 10 days, he had received a daily dose of intramuscular nandrolone (Deca-Durabolin 50 mg), but was not taking any other medication. A chest X-ray showed a pleural effusion occupying 30% of the left hemi-thorax. His physical examination, blood count and serum biochemistry were otherwise unremarkable. A thoracentesis obtained clear fluid, exudative by lactate dehydrogenase (LDH) and protein levels, (310 UI/l and 4,8 gr/dl respectively) normal pH (7,46) and predominantly eosinophils (30%) in the leukocyte differential count (2500 cell per cubic milliliter) and 50% lymphocytes and 20% neutrophils. No peripheral blood eosinophilia was found. AFB staining of the pleural fluid was negative and the ADA level was normal (21 UI/L). The patient gave no history of TB contact and a TST was negative (0 mm). Culture of the pleural fluid for bacteria on blood agar and for mycobacteria on Lowenstein Jensen and Stonebrink medium was negative. A parasitic infection was suspected but serial stool examinations were negative for parasites. No definitive diagnosis was made, but malignant pleural effusion was suspected. After thoracentesis the patient felt better and did not return to the hospital until 4-months later, when he returned to the emergency room with similar pleuritic symptoms, fever and night sweats. Additionally, he had a nonproductive cough and had lost more than 5 kilograms in weight since the previous visit. Examination of the lungs revealed decreased breath sound in the lower left hemi-thorax, but the rest of the physical examination was normal. A chest X-ray again showed the left sided pleural effusion, slightly smaller than on the previous study. A second thoracentesis obtained turbid fluid, pH 7 41, 3100 cells per cubic millimeter, 90% mononuclear and 3% eosinophils, 5,4 gr/dl proteins and 242 UI/dl LDH. Glucose, amylase levels, hematological parameters, renal and hepatic serum tests were normal. The effusion/serum ratio for proteins and LDH were 0 77 and 0 83 respectively. The ADA on the pleural fluid was elevated (51 U/L) and suggestive of tuberculosis, and the TST was positive (20 mm). Ziehl-Neelsen staining for AFB was negative both on induced sputum and pleural liquid. A pleural biopsy showed a chronic pleurisy with multiple granulomas with central necrosis, compatible with pleural TB and a culture of the pleural tissue was positive for M. tuberculosis after 4 weeks. The patient's symptoms disappeared after starting treatment with anti-tuberculosis drugs, and the chest X-ray showed resolution of the effusion 4 weeks later, turning completely normal.

PMC5748127_01

Male

A 37-year-old Portuguese man, heavy smoker, with a history of alcohol and drug abuse, and concomitant HIV infection (CD4+T cell count 360 cells/muL) under highly active antiretroviral therapy since 1998, was currently medicated with efavirenz, emtricitabine, and tenofovir. One year before presentation, he had a TB contact and was not screened for active or latent TB infection. He was admitted due to a two-month history of severe back pain, with no constitutional or respiratory symptoms and no neurological signs. Magnetic resonance imaging (MRI) of the spine revealed peripheral lesions located at T9-T10 vertebral bodies, associated with discreet compression of spinal cord, small paravertebral abscess, and empyema. A percutaneous biopsy was performed. The microscopy smear of the acid-fast bacilli (AFB), the nucleic acid amplification test (NAAT), and the culture of Mycobacterium tuberculosis (MT) were positive, with no drugs resistance. The patient was started on isoniazid (H), rifampin (R), pyrazinamide (Z), and ethambutol (E) (HRZE) for 4 months, due to slow radiological resolution of the vertebral lesions, and remained in therapy with HR for 2 years. He currently has no symptoms or significant vertebral sequelae.

PMC5748127_03

Male

A 23-year-old Portuguese man, smoker, HIV negative, with recent multidrug-resistant tuberculosis (MDR-TB) contact, presented with acute lower back pain with radiation to the right flank. There were no respiratory, constitutional, or neurological symptoms. Abdominal computerized tomography (TC) showed a retroperitoneal perirenal abscess. Empiric antibiotic treatment and surgical drainage were performed. After 4 months of persistent symptoms, a MRI of the spine was done, which showed instability of the spine due to total lytic bone destruction of T11 and T12 vertebral bodies, focal lytic lesions at bodies T5-T10 bodies, perivertebral abscesses, and also a psoas abscess. A percutaneous biopsy revealed MT (AFB and culture positive). Molecular testing for drug resistance was positive to isoniazid and rifampicin. No other resistance was observed in culture with drug sensibility tests. Other organ involvement was excluded. Surgical stabilization with an autograph reconstruction of T11 and T12 was performed. The patient started an anti-MDR TB therapy with pyrazinamide, ethambutol, amikacin, levofloxacin, ethionamide, and cycloserine. He finished treatment after two years. He has now a moderate chronic back pain and vertebral body loss although with no kyphotic deformity.

PMC8077360_01

Male

A 50-years-old male patient presented to the emergency room complaining of itching, red-eye, and tearing of both eyes. His past medical history was positive for asthma. Past ophthalmologic history was unremarkable. Visual acuity was 20/20 in both eyes. Anterior segment biomicroscopy revealed bilateral mild hyperemia and follicular reaction in the inferior conjunctival fornix. At his first visit, he presented conjunctival pseudomembrane in his right eye, and the diagnosis of a presumable viral conjunctivitis was assumed based on clinical findings. We prescribed preservative-free lubricant eye drops and advised the patient about the contagious risk associated. Patient returned 1 week later complaining of worsening symptoms in his right eye. He presented with painful swelling of the superior and inferior eyelids, yellowish mucopurulent discharge, and decrease of vision in this eye. Visual acuity decreased to hand motion in the right eye and remained 20/20 in the left eye. The slit-lamp exam was impaired in the right eye due to the lids swallow. We noticed mucopurulent discharge, diffuse hyperemia with conjunctival necrosis, and a dense yellowish membrane covering the anterior surface (Fig. 1a). Visualization of the cornea and the anterior segment were compromised. The left eye showed a mild follicular reaction, but cornea, lens, and the anterior chamber were normal. Conjunctival scraps of the mucopurulent discharge and the conjunctival lesions were performed. Bacterioscopy showed gram-positive cocos. Microbiology revealed Streptococcus pyogenes growth which was responsive to most of the antibiotics tested. We performed a debridement of the necrotic conjunctival tissue. During the procedure, we noticed that there was a conjunctival ulcer with necrotic tissue affecting the Tenon's capsule, but preserving the sclera (Fig. 1b). Conjunctival and Tenon biopsy showed an exudative chronic conjunctivitis. Orbital computerized tomography images were suspicious of post-septal involvement. The patient was hospitalized and medicated with systemic antibiotics (ceftriaxone and clindamycin). Topical 0.5% moxifloxacin and 1% prednisolone acetate eye drops were prescribed right after systemic treatment was initiated. Due to the possibility of an autoimmune disease as a differential diagnosis, we performed a rheumatologic workup, but all ancillary exams related were negative. Patient was also tested for infectious diseases including HIV, syphilis, cytomegalovirus, tuberculosis, and hepatitis, but all tests were negative. Patient-reported significant improvement of his symptoms 4-5 days after antibiotic therapy was initiated. The visual acuity improved to 20/20 in the right eye. There was a mild conjunctival hyperemia with remarkable improvement of the ulceration (Fig. 1c). Clinical and functional recover was achieved after 2 weeks of treatment. Topical preservative-free artificial tears were maintained for 2 months.

cellulitis, conjunctivitis, streptococcus pyogenes, tenon capsule

PMC9427261_01

Male

A 62-year-old man of Indigenous Australian background presented to hospital with reduced level of consciousness, dense right hemiplegia, and expressive aphasia. He lived in shared accommodation and was last seen well 3 days previously. The history was that at a welfare check, he was found semiconscious. At triage, his GCS was 11. He had respiratory rate of 40 breaths per minute, temperature of 38.1 C, oxygen saturation was 96%, and heart rate was 114 beats per minute. He was alert but aphasic and had right hemiparesis involving the arm and leg, right hypertonia, and hyperreflexia with positive right Babinski reflex. Due to his aphasia, history was limited and he had no available contacts or regular medical practitioner to obtain other information. Health department records included consultations four years previously for right leg cellulitis. It was reported at the time that he smoked tobacco and occasional marijuana and methamphetamine. Subsequent review of records from another hospital indicated a history of DVT three years previously. He had recently received his first dose of the AstraZeneca COVID-19 vaccine five days prior to admission. State health policy at the time was to perform COVID testing on patients who were febrile or who had respiratory symptoms. The patient was tested for COVID-19 with the Xpert Xpress SARS-CoV-2 real-time PCR assay. This test was positive, and the patient was isolated with airborne precautions thereafter. Initial blood tests revealed a white cell count of 17 x 109/L, CRP of 80 mg/L, platelet count of 377 x 109/L, and creatinine of 121 micromol/L. CT brain and CT angiography-circle of Willis scanning revealed extensive low attenuation in the left MCA and ACA territories, suggestive of extensive ischaemic infarction in these areas (Figure 1). Contrast angiography revealed diminutive M2 branches of the left MCA which appeared intact. No CT evidence of occlusive thrombus was present. The stroke team was involved, and as part of the acute stroke pathway, he was transferred to a tertiary referral hospital. He was admitted to their high dependency unit (HDU) for treatment of the multiterritorial ischaemic infarcts including intracranial pressure monitoring and treatment of COVID-19. Initial chest X-ray showed possible "increased density" on the left lung. Chest X-ray on day 3 confirmed left-sided consolidation. Around this time, he required oxygen supplementation to maintain saturations above 95%. A CTPA was performed to "rule out" pulmonary embolism in view of recent immobility for 3 days and active COVID-19. The CTPA revealed extensive bilateral segmental and subsegmental pulmonary emboli, along with left lower lobe collapse and consolidation, with bilateral patchy ground-glass change (Figure 2). Progress CT brain on day 3 showed petechial haemorrhage in the left frontoparietal MCA territory consistent with haemorrhagic transformation of affected area, with slightly increased mass effect and subfalcine herniation (Figure 3). A decompression hemicraniectomy was considered, although a decision was made for conservative management as the patient's clinical condition suggested against life-threatening raised intracranial pressure. Carotid duplex scanning performed on the same day showed left carotid sinus thrombus causing significant diameter reduction, with a mobile appearance. This was not present on the initial CT angiogram which did not extend proximally enough to cover the carotid sinus. It was initially felt that this could represent a paradoxical embolism, although cardiac abnormalities were subsequently excluded with echocardiography. Standard investigations for the cause of the stroke were unremarkable, with normal random BSL, normal HBa1c, and normal fasting lipids. He was normotensive. Transthoracic echocardiography was essentially normal with normal valvular function, no shunt, and no other abnormal findings. Transoesophageal echocardiography was declined due to the aerosol-generating nature of the study. 24-hour Holter monitoring showed sinus rhythm. Other investigations for a secondary cause of the stroke or pulmonary emboli included tuberculosis gamma interferon release assay and serology for HIV and hepatitis B, all of which were negative. Antinuclear antibody was detected with a weakly positive titre of 1 : 40. Coagulation studies taken before anticoagulation was commenced were within normal limits. Thrombophilia screening was performed including for lupus anticoagulant, antithrombin III levels, protein S, functional protein C, and screening for factor V Leiden and prothrombin variant G20210A. These investigations all yielded normal results. As his platelet counts were consistently within normal limits, he did not meet criteria for testing for Vaccine Induced Thrombosis with Thrombocytopenia Syndrome (VITTS). In accordance with guidelines for use of VITTS testing in use at the time, further evaluation for this condition was not performed. The patient was treated for COVID-19 in accordance with local protocol with dexamethasone for 7 days. The treating neurology team liaised with the COVID-19 team regarding the use of baricitinib; this was commenced on day 5, but continued only for 3 days before being ceased due to a possible increase in thromboembolism associated with baricitinib. Ceftriaxone and doxycycline were also used to treat a likely superimposed bacterial infection in view of the consolidation on chest X-ray. In view of the large cerebral infarct volume with associated haemorrhagic transformation, anticoagulation was not given for the pulmonary emboli or carotid thrombus. Instead, an inferior vena cava (IVC) filter was inserted on day 3 of admission. Aspirin and prophylactic enoxaparin (40 mg at night) were given. Anticoagulation for the carotid thrombus was initially considered unsafe in view of the haemorrhagic transformation. MRI brain was contraindicated due to the presence of the IVC filter. When the haemorrhagic transformation had resolved (confirmed on CT brain on day 38 of admission), anticoagulation with apixaban was commenced along with aspirin. Atorvastatin was added for stroke secondary prevention. After 7 days, a repeat SARS-CoV-2 PCR test was negative and the patient was deisolated after two more PCR tests 24 hours apart. Once stabilised, the patient was transferred to a general medical ward. He was initially poorly responsive and fully dependent. He improved gradually and was able to take oral food so that his nasogastric tube could be removed. He was referred for rehabilitation. At that stage, he had some active movement in the right side and was able to follow one-step commands but had minimal verbal output. The IVC filter was removed, and he was then admitted to the rehabilitation unit for ongoing multidisciplinary care including functional assessment, mobility retraining, and discharge planning. It was recommended that he remain on lifelong anticoagulation. He was admitted to rehabilitation on day 70. Initial FIM score on admission to rehabilitation was 24. There was limited improvement after 3 weeks, and he was put onto a maintenance program whilst awaiting discharge to supported accommodation. At the time of discharge, he had ongoing right hemiplegia, with no functional use of right arm or leg. He required a hoist transfer, being unable to stand independently. He could sit in a wheelchair, but his interest in self-mobilisation was limited. In terms of cognition and communication, he was dysphasic with limited verbal output, although was able to follow at least two-step commands. He could indicate his understanding of simple treatments or information and was judged as being able to give consent or refuse procedures or investigations, although for more complex decisions, the support of a guardian was required. He could feed himself, but required assistance to dress and shower and required assistance with continence management. A repeat carotid arterial doppler performed on day 76 showed resolution of the carotid thrombus, with minimal carotid stenosis. An MRI was performed on day 80 after the IVC filter had been removed; this confirmed the presence of the previously described infarcts. The patient had received quadrivalent influenza immunisation 3 months before this admission, as well as his first dose of the AstraZeneca COVID-19 vaccine. A second dose was given three months later, prior to transfer to rehabilitation, with no adverse effects.

PMC6080573_06

Male

A 43-year-old male patient came to polyclinic with complaints of the difficulty of eating, drinking, and weight loss. The patient came carrying oesophagomaagduodenography (OMD) results from the previous hospital with a diagnosis of suspected achalasia with a differential diagnosis of distal esophageal carcinoma. CT scan and endoscopic examination were performed and the results were within normal limits. The patient had a history of pulmonary tuberculosis treatment. Pulmonary disease is a contraindication for laparoscopy. Laparotomy finger-guided Heller cardiomyotomy with Toupet fundoplication was performed. The duration of the operation was 45 min with minimal bleeding. The patient was evaluated 2 weeks postoperative and showed that he could eat and drink without any complaints. 6 months after surgery the patient had a weight gain of 5-10 kg. The authors attest that full and informed consent was obtained from every single patient who have undergone medical treatment in our Hospital. The informed consent form also declared that patient data or samples will be used for educational or research purposes. This work has been registered in the a publicly accessible database and having a unique identifying number : researchregistry4073. First, we performed surgical procedure under general anesthesia. We made an upper midline incision. Then we did a general exploration of the abdomen while was paying attention to the esophagogastric junction; We mobilized the left hemiliver by dividing the triangular ligament to expose the lower esophagus; Then, we divided the small bands between the stomach and spleen to avoid tearing of the splenic capsule and divide the peritoneum over the esophagus, then retracted the stomach downward; We divided the gastro-hepatic ligament, phrenoesophageal ligaments and excised the esophageal fat pad and crus medial and lateral diaphragm to allow downward mobilization of the esophagogastric junction; A 1.5 cm incision at the gastric corpus was made andthen we inserted an index finger through the incision that has been made into gastric lumen, continued to esophagogastric junction, then into esophagus.We then felt the constricted (spasmodic) lumen. With finger guiding, we divided all the circular and longitudinal muscle fibers to make the myotomy above the area of constriction until the esophageal mucosa is visible. The myotomy incision was extended 4 cm into the esophagus and 2 cm into the gastric cardia to reduce outflow resistance. The evaluation was done by feeling with the finger that the distal esophagus is loosened and the muscle spasm is released then we gave normal saline liquid through the nasogastric tube into the esophagus by closing the cardia area to ensure no mucosal leakage and the mucosa should have been seen bulged. The illustration of the technique is shown in Fig. 1. Finger-guided Heller Cardiomyotomy Procedure:

case series, esophageal achalasia, finger-guided esophagocardiomyotomy, laparoscopy, prevention

PMC2810601_01

Male

A 28-year-old male was admitted to our hospital with a-two-month history of diarrhea, abdominal pain, weight loss, fever, and fatigue. His medical history revealed 3 to 5 episodes of diarrhea each year and recurrent respiratory tract infections since the age of 14 years old. He had been succesfully treated for postprimary cavitary pulmonary tuberculosis (acid-fast bacteria in smears of sputum and sputum culture positive for Mycobacterium tuberculosis in Lowenstein media) and had been given isoniazid (300 mg/day), rifampicine (600 mg/day), ethambutol (1.5 g/day) and pyrazinamide (2 g/day) for 2 months, followed by isoniazid and rifampicine for 10 more months, until 2 months prior to his hospitalization. His condition rapidly deteriorated with the above mentioned symptoms apparent 2 months after cessation of antituberculosis therapy. Physical examination revealed a severely malnourished male with a temperature of 39C; blood pressure 100/60 mmHg; and a heart rate of 96/min. Abdominal examination revealed increased bowel sounds and slight abdominal tenderness. Laboratory studies disclosed: hemoglobin, 14.3 g/dL; WBC, 15,600/microL; platelets, 308,000/microL; ESR, 60 mm/h; CRP, 41.4 mg/dL (normal 0-5); total protein, 5.1 g/dL; and albumin, 2.7 g/dL. Other biochemical data was normal. Urinalysis revealed 4+ proteinuria with oval fat bodies in the sediment. Creatinine clearance was 93 mL/min and proteinuria was 9 g/d. Serum immunoglobulins were as follows: IgG, 168 mg/dL (normal 800- 1700); IgM, 8.95 mg/dL (normal 50-320); IgA, 10.2 mg/dL (normal 85-450); and, IgE, 28.7 IU/mL (normal 0-100). C3 complement was 54.3 mg/dL (normal 50-90). Anti-gliadine IgA and IgG were both negative. CD4/CD8 ratio, CD3, CD56 were normal and tuberculin skin test was positive (17 mm induration). Neutrophil function tests (chemotaxis, phagocytosis, oxidative burst) were within normal limits. Chest X-ray and ECG were normal. Cultures of blood and urine were negative. Numerous erythrocytes and leucocytes were seen in the stool specimen, but stool cultures for Salmonella, Shigella and Campylobacter were negative. Toxin A was negative in the stool. Serologies for HIV, HBV, HCV were negative. Anti-HSV, anti-EBV and anti-CMV IgM's were also negative. Thoracic CT revealed old fibrotic scars in the upper lobes of both lungs, suggesting healed tuberculosis. Abdominopelvic CT was normal. On radiologic examination of the small bowel, there was dilatation and increased mucosal thickness of valvula conniventes. Gastroduodenoscopy was normal; multiple biopsies were obtained and duodenal aspiration was performed. Rectosigmoidoscopy was nondiagnostic. Histologic examination of esophageal, duodenal, colon (Fig. 1) and gastric (Fig. 2) biopsies revealed extensive, subepithelial, Congo red positive amyloid deposition. Disappearance of these after adding KMnO4 suggested AA amyloidosis, also confirmed by immunohistochemical staining. In addition, the four currently identified mutations of MEVF gene on exon 10, associated with familial Mediterranean fever (FMF) -which are M694V, M694I, M680I, V726A,- were negative. Ciprofloxacine (200 mg, bid, i.v.) and metronidazole (500 mg, bid, i.v.) were commenced. The patient's clinical condition started to improve within a few days and returned to normal at 3 weeks. The antibiotics were then discontinued and the patient was discharged. Two weeks later, diarrhea with 3-4 bowel movements/day developed, and repeated diagnostic tests revealed no specific cause. Metronidazole was recommended for 3 further months during which the patient's diarrhea disappeared and he put on 18 kg but hypogammaglobulinemia and nephrotic-range proteinuria persisted. Later, colchicine 1.5 mg/day was administered to hopefully control proteinuria. At the end of the third year of follow-up; the patient was still using colchicine and also metronidazole (500 mg, bid, p.o.) for one week every month or in the case of > 3 mushy stools/day lasting > 3 days. The control gastroscopy and rectosigmoidoscopy were normal: biopsies showed AA amyloid infiltration. Although the patient had hypogammaglobulinemia, his condition did not worsen except for recurrent upper respiratory tract infections, a recent acute attack of chronic otitis media, and chronic recurrent diarrhea. The patient's creatinine clearance was normal, but the proteinuria was still in the nephrotic range.

PMC4900058_01

Male

This year, the 27-year-old patient returned again with the same upper respiratory symptoms, and was found to have decreased oxygen saturation. A chest x-ray revealed diffuse reticular opacities. A chest CT revealed predominantly upper-lobe bronchiectasis, with diffuse tree-in-bud opacities (Fig. 4). Although the patient did not have gastrointestinal complaints, transient intussusception of the small bowel was noted as well as dilation and severe fecal impaction within the large bowel (Fig. 5A). The pancreas was diffusely atrophic and showed marked fatty replacement (Fig. 5B). With continued abnormal liver lab results, he received subsequent testing for alpha-1 antitrypsin deficiency and sputum for tuberculosis, both of which were negative. In worsening condition, our patient recently provided sputum for gram stain and culture. The gram stain showed gram-positive cocci in pairs, chains, and clusters, as well as gram-negative bacilli. The culture grew Pseudomonas fluorescens, a rare bacterium documented in immunosuppressed individuals. Immunofixation analyses also showed increased levels of immunoglobulin G, sometimes associated with chronic infection. It is clear that our patient suffers from an adult-onset form of CF, with elevated sweat chloride level and no known CFTR mutation. To this day, our patient's condition deteriorates, and he remains with no documented diagnosis of CF. Insurance coverage for diagnostic testing generally follows nationally established health guidelines, which are designed to identify the disease in the vast majority of cases. However this strategy excludes coverage for new clinical profiles such as atypical CF, late-onset CF, and CF not testing positive against standard mutation and sweat chloride analyses.

cf, cystic fibrosis, ct, computed tomography, mri, magnetic resonance imaging

27-year-old African-American male with late-onset cystic fibrosis. Axial views of contrast-enhanced reformatted chest CT. A) Localized dilation of the bronchi reveals upper-lobe bronchiectasis (arrow). Peribronchial cuffing demonstrates extent of inflammation and mucous impaction.

PMC4900058_01

Male

This year, the 27-year-old patient returned again with the same upper respiratory symptoms, and was found to have decreased oxygen saturation. A chest x-ray revealed diffuse reticular opacities. A chest CT revealed predominantly upper-lobe bronchiectasis, with diffuse tree-in-bud opacities (Fig. 4). Although the patient did not have gastrointestinal complaints, transient intussusception of the small bowel was noted as well as dilation and severe fecal impaction within the large bowel (Fig. 5A). The pancreas was diffusely atrophic and showed marked fatty replacement (Fig. 5B). With continued abnormal liver lab results, he received subsequent testing for alpha-1 antitrypsin deficiency and sputum for tuberculosis, both of which were negative. In worsening condition, our patient recently provided sputum for gram stain and culture. The gram stain showed gram-positive cocci in pairs, chains, and clusters, as well as gram-negative bacilli. The culture grew Pseudomonas fluorescens, a rare bacterium documented in immunosuppressed individuals. Immunofixation analyses also showed increased levels of immunoglobulin G, sometimes associated with chronic infection. It is clear that our patient suffers from an adult-onset form of CF, with elevated sweat chloride level and no known CFTR mutation. To this day, our patient's condition deteriorates, and he remains with no documented diagnosis of CF. Insurance coverage for diagnostic testing generally follows nationally established health guidelines, which are designed to identify the disease in the vast majority of cases. However this strategy excludes coverage for new clinical profiles such as atypical CF, late-onset CF, and CF not testing positive against standard mutation and sweat chloride analyses.

cf, cystic fibrosis, ct, computed tomography, mri, magnetic resonance imaging

27-year-old African-American male with late-onset cystic fibrosis. Axial views of contrast-enhanced reformatted chest CT. B) Tree-in-bud opacities appear within the lungs (arrow). Note the narrowed mediastinum.

PMC8420644_01

Female

In February 2021 (day 0), a 56-year-old Ugandan woman presented to the Infectious Disease Unit of Kiruddu National Referral Hospital, Uganda, with a two-month history of mild-to-moderate, on-and-off headaches, which were worse in the mornings and were associated with neck pain, nausea, and blurred vision. She denied any history of convulsions, fever, vomiting, photophobia, diplopia, altered level of consciousness or impaired hearing. Her past medical history is significant for HIV-1 infection diagnosed in 2006 for which she was commenced on Zidovudine (AZT), Lamivudine (3TC) and Efavirenz (EFV) as first-line antiretroviral therapy. She was also diagnosed with systemic arterial hypertension in 2014, managed with bendroflumethiazide (5 mg once daily). She reported good adherence to antiretroviral therapy as well as her antihypertensive medication. Her initial antiretroviral therapy regimen (AZT/3TC/EFV) was programmatically switched to Tenofovir Disoproxil Fumarate (TDF), 3TC, and Dolutegravir (DTG) regimen and her cotrimoxazole (CTX) prophylaxis discontinued in May 2019 since she had undetectable HIV RNA viral load and her CD4+ T-cell count at the time was 767 cells per microliter. In January 2020 (day -364), she was diagnosed with asymptomatic cryptococcal antigenemia (she had a positive serum CrAg and a negative cerebrospinal fluid CrAg). She completed 24 weeks of fluconazole and was well and asymptomatic. Eight months prior to admission (day -224), she received isoniazid as tuberculosis preventive therapy. On admission (day 0), her vitals were as follows: axillary temperature - 36.0 C, pulse rate - 83 beats per minute, blood pressure - 130/74mmHg and respiratory rate - 14 breaths per minute. On further physical exam, she was in fair general condition, conscious and alert, and fully oriented in person, place and time. Neurological exam revealed a Glasgow coma scale of 15/15, no obvious craniopathies, her neck was stiff. However, both Kernig's and Brudzinski's signs were negative. Muscle tone, bulk, tendon reflexes, and sensation were normal. Other systemic examination was unremarkable. On day 0, both serum and cerebrospinal fluid CrAg lateral flow assay tests (IMMY, Oklahoma, USA) were negative, despite serial dilutions. CD4+ T-cell count was 766 cells/microliter and HIV RNA viral load was undetectable abdominal ultrasound and chest x-ray were normal and the Urine lipoarabinomannan lateral flow assay was negative. Given the high index of suspicion, a lumbar puncture was ordered and results are as shown in Table 1. Her admission hemoglobin was 12.8g/dL, platelet 219 x10^3/microL and white cell count of 5.5 x10^3/microL with normal differentials. The rest of the full hemogram parameters were normal. Baseline renal and liver biochemistries were within normal limits. India ink preparation and quantitative cultures on Sabouraud agar were suggestive of Cryptococcus spp, (Figure 1) supporting the diagnosis of cryptococcal meningitis. On day 1, she was commenced on intravenous amphotericin B deoxycholate (1mg/kg) for 3 days (considering 10 CFU growth of Cryptococcus spp) in combination with oral flucytosine (100mg/kg) for 7 days and then fluconazole 1200mg once daily for the next 11 days. By day 7, she was symptom free and quantitative cerebrospinal fluid culture was negative for Cryptococcus spp. She was discharged on day 9. At 10 weeks (day +40) and 18 weeks (day +72), she was well and adherent to her antiretroviral therapy and on maintenance phase of cryptococcal meningitis on fluconazole at a dose of 400mg once daily.

india ink, amphotericin b, cryptococcal antigen test, cryptococcal meningitis, fluconazole, flucytosine

PMC6396576_01

Female

A 42-year-old female patient, farmer by occupation, resident of Chamba district, presented to our outpatient department with chief complaints of fever for 2 months and right-sided chest pain for the same duration. The patient was apparently well before that when she presented with fever documented up to 102 Fahrenheit with evening rise in temperature and it was associated with night sweats but not associated with any chills and rigor or any rash or skin changes. Her right-sided chest pain was localized to infra-axillary region, nonradiating, sharp, nonexertional, and got aggravated on deep inspiration and coughing. There was no history of cough and shortness of breath. Ten years ago, she took treatment for lymph node (LN) TB but defaulted after 3 months of therapy. She never took any medication for diabetes and hypertension. There was no history suggestive of any contact with TB patient, or high-risk sexual behavior. Family history, menstrual history, and recent treatment history were unremarkable. On examination, the patient had pallor and mild dependent edema. Five LNs were palpable in the right cervical region superior and middle cervical region, the largest being 2.5 cm in diameter, matted, nontender, and not associated with any overlying skin changes not fixed to the underlying structure or skin. On respiratory system examination, the right infra-scapular and infra-axillary region were dull on percussion and breath sounds were decreased with shifting dullness suggestive of right-sided pleural effusion, which was confirmed by chest X-ray. About 5 mL of straw colored fluid was tapped and sent for investigation. Investigations revealed the following: Hb 8.9 g/dL, total leukocyte count 4970 (neutrophils 76%, lymphocytes 15%, eosinophils 5%, basophils 3%, monocytes 1%), platelet 320,000, serum glutamic oxaloacetic transaminase 44, serum glutamic pyruvate transaminase 34, bilirubin total 0.8, albumin 3.9, alkaline phosphatase 128, urea 96, creatinine 1.9, Na 143, K 4.5, calcium 11.3 mg/dL, phosphorous 4.9, serum and urine electrophoresis was negative, intact parathyroid hormone 20 ng/L (8-51 pg/mL), arterial blood gas showed pH of 7.38, 25(OH) vitamin D 97 ng/mL (30-100 ng/mL), angiotensin converting enzyme level 10 U/L, urine routine and microscopy were normal, and urine for acid fast bacilli was negative. Urinary calcium level was higher than normal (U Ca/Cr = 32). Chloride level was 23 mmol/L. Ultrasonography KUB and noncontrast computed tomography KUB [Figure 1] were suggestive of medullary macro-calcification without any evidences of renal TB. Renal biopsy [Figure 2] was done showing interstitial deposition of calcium without any histological evidences for renal parenchymal TB. Intravenous pyelogram was done and it did not reveal any lesion suggestive of genitourinary TB. LN biopsy revealed caseating granulomatous change with Genexpert (CB-NAAT) positive. Pleural fluid was exudative, and lymphocyte was predominant (95%) with adenosine deaminase level of 67 ng/mL. Hence, a diagnosis of extrapulmonary TB was made.

extrapulmonary tuberculosis, hypercalcemia, nephrocalcinosis

PMC6396575_01

Male

A one-year-old boy presented with evening rise of fever for 20 days and cough for 15 days. There was no loss of weight or contact with TB. He was investigated for the same, and the chest X-ray was suggestive of hyperinflation of right lung and shift of mediastinum to left side. A computed tomography (CT) chest with virtual bronchoscopy showed intraluminal right main bronchus necrotic lymph node with patchy consolidation in right middle and lower lobe. Bronchoalveolar lavage did not grow tuberculous bacillus on culture. Child was started on four drugs anti-tuberculous therapy (ATT) consisting of isoniazid (H), rifampicin (R), ethambutol (E), and pyrazinamide (Z) for 2 months and HR for next 7 months. He gained 3 kg weight in the 9-month ATT regime, and X-ray chest on follow-up was absolutely normal.

anti-tuberculous therapy, bronchoscopy, bronchostenosis, endobronchial tuberculosis, infants

PMC6396575_02

Male

A 6-month-old boy presented in July 2009 with breathlessness for 8 days and cough, fever for 3 days. There was no foreign body aspiration or contact with TB. On examination, weight was 6 kg, height was 62 cm, and there was decreased air entry on the right side with shift of mediastinum to left side. Other systems were normal. Chest X-ray showed obstructive emphysema on right side with shift of mediastinum to opposite side. A CT chest with virtual bronchoscopy showed an endobronchial lesion in the distal right main bronchus causing obstructive emphysema with enlarged necrotic mediastinal lymph nodes suggestive of TB. All family members were screened for TB and maternal uncle was detected to have cavity in right mid zone. The child was started on four drugs ATT consisting of HRZE along with prednisolone (2 mg/kg/day) which were tapered gradually. In September 2009, his weight was the same and chest X-ray was also the same. CT chest showed persistence of endobronchial lesion and increase in size of mediastinal nodes. He underwent a bronchoscopy and TB culture was negative. In February 2010, his weight increased to 9 kg and in July 2010, his chest X-ray was normal. ATT was stopped in July 2010. He received ATT for 12 months in view of delayed response to ATT.

anti-tuberculous therapy, bronchoscopy, bronchostenosis, endobronchial tuberculosis, infants

PMC6396575_03

Male

A 2-month-old boy presented with fever for 20 days along with breathlessness. There is no contact with TB. On examination he had decreased air entry on left side with shift of mediastinum to opposite side. Chest X-ray showed right upper zone pneumonia with mediastinal adenopathy and obstructive emphysema on the left side. CT chest showed necrotic mediastinal adenopathy with extrinsic compression of left main bronchus with resultant obstructive emphysema of left lung. Mantoux test was positive. Child was started on four drugs ATT with steroids. At 4 months of age, he weighed 5.25 kg and at 6 months was 6 kg. On follow-up, he was asymptomatic and ATT was stopped after 6 months.

anti-tuberculous therapy, bronchoscopy, bronchostenosis, endobronchial tuberculosis, infants

PMC6688143_01

Male

A 65-year-old male patient presented to our clinic with pain, swelling and sensitivity in the left leg. The patient had experienced a trauma to the same leg 12 years ago, but did not develop any impairments in the integrity of the skin. A year after the trauma, he experienced pain, swelling and sinus leakage. Diagnosed with bone infection, the patient had undergone antibiotherapy. Complaints of the patient have increased in the last 6 months with occasionally increasing pain. Chronic sinus orifice, pain, edema and minimal temperature increase were observed in the medial leg at the diaphyseal-metaphyseal junctional region of the tibia during physical examination. No fever was detected. The patient was a laborer in the low-middle range income level. He was a smoker and had chronic kidney problems. He had received Bacillus Calmette-Guerin (BCG) injections, and his family had no history of tuberculosis. Appearance of a sequelae lesion in the lung radiographs and calcification and pleural thickness in the thorax on the computed tomography (CT) images were observed. Erythrocyte sedimentation rate, C-Reactive protein (CRP) and leukocyte values were 36 mm/h, 7.15 mg/dL and 10.05 x 1000 microL, respectively. The purified protein derivative (PPD) test result was negative. Intramedullary sclerosis accompanied by cortical thickness and multifocal radiolucent areas were observed in the direct roentgenograms, starting from the tibia, below the diaphyseal region, and extending to the metaphyseal region (Figure 1). The maximum intensity projection (MIP) method was employed in the examination of the leg with the Multidetector Computed Tomography (MDCT; Aquilion 64; Toshiba Inc., Tokyo, Japan). In the metaphyseal-diaphyseal region, a significant cortex thickness with an irregular contour and an accompanying periosteal reaction were observed. In the intramedullary region, areas surrounded with a sclerotic halo and a high fluid density were detected (Figure 2). Magnetic resonance imaging (MRI) was performed using the Signa 1.5T HDxt MR system (GE Healthcare, Chicago, IL, USA). On T1-weighted coronal images, a hypointense serpiginous appearance, which is typical for Brodie's abscess, in the metaphyseal-diaphyseal region of the tibia was seen (Figure 3). On T2-weighted images, a hyperintense intramedullary cavitary lesion, which can be considered as a demonstrative sign for Brodie's abscess, was detected (Figure 4). On contrast-enhanced fat-suppressed images, pre-contrast imaging revealed multifocal hypointense lesions, as post-contrast images showed diffuse peripheral contrast enhancement reminiscent of abscess. The heterogeneous contrast enhancement in the soft tissue was thought to be due to inflammation and edema (Figure 5). Ziehl-Neelsen staining and Gram staining were performed on the samples taken with injection; however, no pathogen was detected. In addition, no pathogen was isolated from the culture samples. Broad-spectrum antibiotics were started considering pyogenic osteomyelitis. The patient's complaints did not resolve with medical treatment; biopsy was performed followed with curettage and antibiotic cement (Vancomycin; 4 grams added to 40 grams cement package) application. On histopathological examination, caseating granulomas with Langhans giant cells and a mixed inflammatory cell infiltration were seen. Dead bone fragments (sequestra) were present within the inflamed granulation tissue (Figure 6). Acid-fast bacillus (AFB) staining did not reveal any bacilli. However, M. tuberculosis-specific DNA was detected by real-time polymerase chain reaction (Real-Time PCR; Anyplex MTB/NTM Real-time Detection Kit, CFX96 Real-Time PCR System; Seegene, Inc., Seoul, South Korea) performed on formalin-fixed paraffin-embedded (FFPE) tissue block (Figure 7). The M. tuberculosis complex was produced from the perioperative samples in the Lowenstein-Jensen medium after 5 weeks. The patient was treated with anti-tuberculosis treatment (Isoniazid 1 x 300 mg, Rifocin (Rifamycin) 1 x 600 mg, Ethambutol 1 x 1500 mg and Pyrazinamide 1 x 1500 mg for 3 months and then Isoniazid 1 x 300 mg and Rifocin 1 x 600 mg for 3 months). At the first year follow-up, the clinical, radiological and laboratory findings were normal.

brodie’s abscess, real-time polymerase chain reaction, tibial diaphyseal osteomyelitis, tuberculous osteomyelitis

PMC7424375_01

Female

A 32-year-old woman, G1P1001, presented with two years of increasing abdominal distension. She had also experienced poor appetite and weight loss. Her menstrual period was regular, and she had neither abnormal vaginal bleeding nor pelvic pain. Six years prior to this visit, she experienced chronic pelvic pain and had been treated with injectable progestin for clinical suspicion of pelvic endometriosis. One year prior to this visit, she had visited the provincial hospital due to abdominal distension. A computerized tomography (CT) scan of the abdominopelvic region revealed a large amount of ascites with peritoneal nodule and pleural effusion. Abdominal paracentesis and pleural tapping were performed, which indicated exudative fluid, but no malignant cells were noted. She was then referred to another hospital for further work-up. Another CT scan of the abdominopelvic region was performed, which revealed circumferential wall thickening at the mid to upper rectum suggesting rectal cancer with a large amount of ascites and right pleural effusion. Colonoscopy and tissue biopsy at the rectum showed only acute colitis with no dysplasia or malignancy detected. However, she did not return to follow up after this operation. Upon presentation at our hospital, the patient appeared chronically ill and emaciated with a body mass index of 14.9 kg/m2. Her abdomen was markedly distended due to a large amount of ascites (Figure 1). There were no masses or pain upon palpation. Vaginal examination revealed bulging of the anterior vaginal wall due to ascites with no palpated pelvic mass. A CT scan of the abdominopelvic region performed at our hospital showed infiltrative enhancing lesions involving the cul-de-sac and perirectal region with massive loculated ascites and internal septation. The uterus and both ovaries appeared unremarkable (Figure 2). A chest X-ray revealed bilateral pleural effusion and passive atelectasis of both lower lobes. Her CA-125 level was 112 IU/mL, CA19-9, and CEA levels were within the normal range. We performed abdominal paracentesis, which yielded a clear yellowish fluid. Cytologic examination suggested inflammation without malignant cells. The ascites sample was also sent for tuberculosis PCR and acid-fast bacilli staining, both of which were negative. Exploratory laparotomy was scheduled for tissue diagnosis. Upon laparotomy, we noted a large amount of serosanguinous ascites, thickened matted bowel loops, and necrotic debris covering the entire peritoneal surface (Figure 3). The right adnexa and uterus were partially identified. No gross focal mass lesions were found. The surgical procedures included drainage of 6.5 liters of ascites, lysis adhesion, biopsy of the peritoneum, and right salpingo-oophorectomy. Histologic examination of peritoneum tissue showed benign endometrial glands with stroma deposited within a thick fibrous tissue and chronic inflammation background (Figure 4). Immunohistochemical studies of peritoneal tissue showed positive staining for estrogen receptor (ER) and progesterone receptor (PR) within the foci of endometriosis. Endometriotic foci at the broad ligament were found adjacent to an unremarkable right fallopian tube (Figure 5). Sections of the right ovary were unremarkable. There were no malignant cells in any of the tissues examined. Cytologic examination of ascites fluid revealed inflammation without malignant cells. A final diagnosis of endometriosis was made based on these pathological and cytological findings. The patient's postoperative course was uneventful. GnRH analog was prescribed for six months postoperatively. The patient has subsequently been on a daily regimen of oral progestin. At fifteen months following the operation, the patient had no symptoms and the results of a physical examination were unremarkable.