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PMC3707284_01

Female

A 78-year-old Caucasian (Greek origin) female patient presented with an 8-day history of nausea, multiple bilious vomiting episodes, anorexia, discomfort in the right hypochondrium and epigastrium and fever up to 38,5 C. On physical examination the patient was in bad condition with affected facet, pale skin and mucosae, signs of dehydration, tachypnoea, tachyarrhythmia and fever (39 C), while the abdomen was soft, nontender, mildly distended and painful on palpation of the epigastrium and right upper quadrant. Her medical history included a HCV infection, arterial hypertension, chronic atrial fibrillation, diabetes mellitus type 2, stroke with residual left hemiparesis, hypothyroidism, hyperlipidaemia and consumption of NSAIDs over the previous week. Laboratory examinations revealed a white blood cell count of 10.72 (x109/L), Neu 88.5%, toxic granulation of polymorphonuclears, a C-reactive protein of 72.7 (IU/L), Glu 139 (IU/L), Urea 73.4 (IU/L), Crea 1.38 (IU/L), gammaGT 87 (IU/L), tBIL 1.37 (IU/L), dBIL 1.10 (IU/L), and LDH 517 (IU/L). The chest X-ray revealed a possible aspirational pneumonia. The abdominal X-ray was suspicious for presence of air in the gallbladder (Figure 1). On abdominal U/S the gallbladder could not be well visualised, the presence of air in the intrahepatic bile ducts was suspected and no dilatation of the bile ducts was detected. The stomach was found dilated and filled with liquid. Abdominal CT showed the presence of a gallstone in the 2nd to 3rd part of the duodenum and a dilatation of the first part. The presence of contrast and air in the gallbladder was also noticed. The stomach was found with mild dilatation (Figures 2, 3, 4, and 5). The diagnosis "Bouveret syndrome" was set. A nasogastric tube was placed to decompress the stomach. Initial treatment included administration of fluids, electrolytes and antibiotics. For further topographic information a gastrografin meal was performed. A large gallstone was visualised in the 2nd to 3rd part of the duodenum. The gallbladder, the cystic duct and the cholecystoduodenal fistula as well as a duodenal diverticulum of the 3rd part were well visualised (Figures 6 and 7). The patient was transferred in the endoscopic unit where a gastroduodenoscopy was performed. The fistula orifice was seen (Figure 8) as well as the proximal side of the gallstone (Figure 9). Endoscopic removal and mechanical lithotripsy were attempted using different skills and equipment, but all efforts failed (Figure 10). Surgical treatment was decided. Due to serious comorbidity the patient received high thoracic epidural anaesthesia. A laparotomy with midline incision was performed. The gallbladder was found collapsed and the cholecystoduodenal fistula was identified. A Kocher's manoeuvre was performed and the gallstone was palpated in the 2nd to 3rd part of the duodenum. An initial effort for proximal removal towards the stomach was unsuccessful. With gentle milking movements distal removal was achieved in the first part of the jejunum right after the ligament of Treitz (Figure 11). No further removal was feasible. A jejunotomy and successful removal of the gallstone were performed (Figure 12). The size of the extracted calculus was 5.8 x 3.7 x 4 cm. The jejunotomy was sutured in two layers. The gallbladder and the fistula were left intact. No other stones were detected in the digestive tract. No complications occurred after surgery and the patient was discharged on the 8th postoperative day.

PMC10316221_01

Female

A 42-year-old female presented for pre-operative clearance for a Roux-en-Y gastric bypass. Review of symptoms was negative. Her medical history was significant for morbid obesity, hyperlipidemia, and Type 2 diabetes mellitus. Her surgical history included a hysterectomy performed in another city (for unknown reason at the time of imaging). The patient denied personal or family history of cancer. Pre-operative workup including electrocardiogram and laboratory work (complete blood count, basic metabolic panel, and prothrombin time/international normalized ratio) were unremarkable. Pre-operative chest radiographs revealed numerous small bilateral lung nodules [Figure 1]. Subsequent chest computed tomography (CT) confirmed numerous, well-circumscribed solid nodules throughout bilateral lungs measuring up to 1.2 cm [Figure 2]. At this point, the leading consideration was metastatic disease from an unknown primary site. Pulmonology was consulted. Positron emission tomography (PET)/CT using 18-F fluorodeoxyglucose (FDG) was ordered to assess for metabolic activity in the nodules and to survey for a primary site of disease. No abnormal hypermetabolic foci were present on the PET/CT [Figure 3]. There was no evidence of a hypermetabolic primary neoplasm, and the solid pulmonary nodules demonstrated a maximum standardized uptake value of 1.3 (below mediastinal blood pool activity). Note was made of a prior hysterectomy on the PET/CT and the possibility of BML was suggested. Additional nonhypermetabolic metastatic etiologies were posed, included benign metastasizing meningioma, giant cell tumor of bone (GCTB), and thyroid adenoma. Additional history from the patient revealed, she had obtained the hysterectomy for uterine fibroids. There was a multidisciplinary consensus to biopsy the nodules. The patient underwent video-assisted thoracoscopic surgery with wedge resection of all three lobes of the right lung. Histopathological examination revealed estrogen receptor positive bland spindle cell proliferation with entrapped Type II pneumocytes, consistent with BML [Figure 4]. The patient was referred to gynecologic oncology for further management. A 3-month follow-up CT demonstrated stability of existing nodules, and the patient was started on monthly leuprorelin injections. After an additional 3-months, the patient endorsed minimal side effects from treatment and CT redemonstrated nodule stability. She remains asymptomatic and continues to follow with gynecologic oncology for monthly injections and disease monitoring.

benign, case report, hysterectomy, leiomyoma, metastatic, solid pulmonary nodule

A 42-year-old asymptomatic female with numerous pulmonary nodules. Reformatted coronal computed tomography maximum intensity projection image confirms numerous well-circumscribed solid nodules throughout bilateral lungs measuring up to 1.2 cm (arrow).

PMC10316221_01

Female

A 42-year-old female presented for pre-operative clearance for a Roux-en-Y gastric bypass. Review of symptoms was negative. Her medical history was significant for morbid obesity, hyperlipidemia, and Type 2 diabetes mellitus. Her surgical history included a hysterectomy performed in another city (for unknown reason at the time of imaging). The patient denied personal or family history of cancer. Pre-operative workup including electrocardiogram and laboratory work (complete blood count, basic metabolic panel, and prothrombin time/international normalized ratio) were unremarkable. Pre-operative chest radiographs revealed numerous small bilateral lung nodules [Figure 1]. Subsequent chest computed tomography (CT) confirmed numerous, well-circumscribed solid nodules throughout bilateral lungs measuring up to 1.2 cm [Figure 2]. At this point, the leading consideration was metastatic disease from an unknown primary site. Pulmonology was consulted. Positron emission tomography (PET)/CT using 18-F fluorodeoxyglucose (FDG) was ordered to assess for metabolic activity in the nodules and to survey for a primary site of disease. No abnormal hypermetabolic foci were present on the PET/CT [Figure 3]. There was no evidence of a hypermetabolic primary neoplasm, and the solid pulmonary nodules demonstrated a maximum standardized uptake value of 1.3 (below mediastinal blood pool activity). Note was made of a prior hysterectomy on the PET/CT and the possibility of BML was suggested. Additional nonhypermetabolic metastatic etiologies were posed, included benign metastasizing meningioma, giant cell tumor of bone (GCTB), and thyroid adenoma. Additional history from the patient revealed, she had obtained the hysterectomy for uterine fibroids. There was a multidisciplinary consensus to biopsy the nodules. The patient underwent video-assisted thoracoscopic surgery with wedge resection of all three lobes of the right lung. Histopathological examination revealed estrogen receptor positive bland spindle cell proliferation with entrapped Type II pneumocytes, consistent with BML [Figure 4]. The patient was referred to gynecologic oncology for further management. A 3-month follow-up CT demonstrated stability of existing nodules, and the patient was started on monthly leuprorelin injections. After an additional 3-months, the patient endorsed minimal side effects from treatment and CT redemonstrated nodule stability. She remains asymptomatic and continues to follow with gynecologic oncology for monthly injections and disease monitoring.

benign, case report, hysterectomy, leiomyoma, metastatic, solid pulmonary nodule

A 42-year-old asymptomatic female with numerous solid pulmonary nodules. (a) 18-fluorodeoxyglucose (FGD) Positron Emission Tomography (PET)/Computed Tomography (CT) maximum intensity projection does not reveal any abnormal hypermetabolic activity.

PMC10316221_01

Female

A 42-year-old female presented for pre-operative clearance for a Roux-en-Y gastric bypass. Review of symptoms was negative. Her medical history was significant for morbid obesity, hyperlipidemia, and Type 2 diabetes mellitus. Her surgical history included a hysterectomy performed in another city (for unknown reason at the time of imaging). The patient denied personal or family history of cancer. Pre-operative workup including electrocardiogram and laboratory work (complete blood count, basic metabolic panel, and prothrombin time/international normalized ratio) were unremarkable. Pre-operative chest radiographs revealed numerous small bilateral lung nodules [Figure 1]. Subsequent chest computed tomography (CT) confirmed numerous, well-circumscribed solid nodules throughout bilateral lungs measuring up to 1.2 cm [Figure 2]. At this point, the leading consideration was metastatic disease from an unknown primary site. Pulmonology was consulted. Positron emission tomography (PET)/CT using 18-F fluorodeoxyglucose (FDG) was ordered to assess for metabolic activity in the nodules and to survey for a primary site of disease. No abnormal hypermetabolic foci were present on the PET/CT [Figure 3]. There was no evidence of a hypermetabolic primary neoplasm, and the solid pulmonary nodules demonstrated a maximum standardized uptake value of 1.3 (below mediastinal blood pool activity). Note was made of a prior hysterectomy on the PET/CT and the possibility of BML was suggested. Additional nonhypermetabolic metastatic etiologies were posed, included benign metastasizing meningioma, giant cell tumor of bone (GCTB), and thyroid adenoma. Additional history from the patient revealed, she had obtained the hysterectomy for uterine fibroids. There was a multidisciplinary consensus to biopsy the nodules. The patient underwent video-assisted thoracoscopic surgery with wedge resection of all three lobes of the right lung. Histopathological examination revealed estrogen receptor positive bland spindle cell proliferation with entrapped Type II pneumocytes, consistent with BML [Figure 4]. The patient was referred to gynecologic oncology for further management. A 3-month follow-up CT demonstrated stability of existing nodules, and the patient was started on monthly leuprorelin injections. After an additional 3-months, the patient endorsed minimal side effects from treatment and CT redemonstrated nodule stability. She remains asymptomatic and continues to follow with gynecologic oncology for monthly injections and disease monitoring.

benign, case report, hysterectomy, leiomyoma, metastatic, solid pulmonary nodule

A 42-year-old asymptomatic female with numerous solid pulmonary nodules. CT , and.

PMC4303604_01

Male

A 12-year-old boy developed his first paroxysmal episode at age 10.5 years. Episodes were triggered by sudden movement after a period of inactivity such as sitting in a car or watching television on a couch. During attacks, there was dystonia of both arms and trunk with flexion of the left elbow and extension of the right elbow, sometimes back arching, typically lasting 5-10 seconds (Video 1). The frequency of the episodes was initially one or two times per month, but subsequently increased to 4-12 times per day without treatment. He did not lose consciousness during the events, and electroencephalography was unremarkable. After one of his dystonic episodes, he developed back pain, and spine imaging revealed grade 2 spondylolisthesis involving the lower back. No other vertebral abnormality was identified. His history was also notable for features of Asperger's syndrome with mild delay in language milestone acquisition, which prompted speech and occupational therapies around age 4-5 years. Motor milestones were normal and there was no history of seizures. He currently attends regular school. He was treated with carbamazepine, up to 250 mg/day, with marked improvement in the frequency and severity of the episodes, but with worsening anxiety. He also had good response to phenytoin but developed swollen gums. Carbamazepine was reintroduced, up to 200 mg/day with improvement, but he then developed leukopenia (white blood cell count of 2,800/microL). He could not tolerate oxcarbazepine, and topiramate was not effective. Genetic testing included Sanger sequencing of the PRRT2 coding regions and flanking splice sites, and whole-genome microarray-based comparative genomic hybridization (aCGH; 180K oligonucleotide + SNP microarray, Agilent Technologies). Although no pathogenic PRRT2 mutations were detected by sequencing, aCGH identified a 533.9-kb deletion on chromosome 16 [arr 16p11.2(29564185-30098069)x1; hg18], encompassing over 20 genes and transcripts and including four Mendelian disease genes (KIFF22, PRRT2, ALDOA, and TBX6) (Figure 1). This proximal 16p11.2 deletion was confirmed by fluorescence in situ hybridization (FISH) using a bacterial artificial chromosome (BAC) probe that hybridized to 16p11.2 and a control probe that hybridized to the subtelomere of chromosome 16q (Figure 1). Both parents subsequently were tested by aCGH and were negative for the aberration, indicating that the 16p11.2 microdeletion occurred de novo in the proband. In addition to the 16p11.2 deletion, aCGH analysis detected a 170.5-kb duplication on chromosome 21 [21q22.11q22.12(34656524-34827038)x3; hg18], including four genes, two of which are Mendelian disease genes (KCNE2 and KCNE1). Parental aCGH analysis indicated that this duplication was paternally inherited, suggesting that it is likely a benign familial copy number variant (CNV).

16p112 microdeletion, paroxysmal kinesigenic dyskinesia, movement disorders

PMC10016364_01

Female

A 29-year-old primiparous Malagasy woman came for a consultation to the dermatological clinic of the Nord Franche-Comte Hospital in June 2020 for painful nodules on her legs typical of erythema nodosum. These lesions developed a month after a swelling of the right breast undergoing etiological investigation. She was not pregnant or lactating. She had last breastfed her child two years ago. She did not use oral contraceptives or any other medication. The patient had no history of tuberculosis infection or autoimmune disease or any family history of breast cancer. A contact with SARS-CoV-2 was noted in April 2020 for which she had not presented any symptoms. On clinical examination, she was not febrile. Voluminous painful tender mass (10x6 cm diameter) was located in upper inner of the right breast with retraction of the nipple (Figure 1). The contralateral breast was unremarkable. The right axillary lymphadenopathy was palpable. The dermatological examination revealed a typical erythema nodosum lesions characterized by multiple erythematous, painful, infiltrated nodules of varying size on the lower limbs (Figure 2). The remaining examination was unremarkable. Biological investigations for an underlying cause such as inflammatory tests (full blood count, erythrocyte sedimentation rate, C-reactive protein), autoimmune markers (antinuclear antibody, anti-DNA, anti-neutrophil cytoplasm antibody) and infective serologies (HIV, hepatitis B and C) were negative or within normal range. Serology SARS-CoV-2 IgG testing as part of a systematic work-up came back positive at over 100. An ultrasound examination, performed twice, showed a hypoechoic mass on the right side, frankly hyper vascularized in favor of mastitis. Mammography did not reveal any suspicious mass or microcalcification. A purulent nipple discharge occurred during the mammography. Breast biopsies showed a lobulocentric subacute mastitis with a non-caseating granulomatous inflammation and multinucleated giant cells (Figure 3a and b). There was no evidence of malignancy. Immunohistochemistry was normal. No organisms were identified on Grocott methanamine silver (GMS), Gram, Periodic acid-Schiff (PAS) and Ziehl-Neelsen stainings. Bacterial, fungal and mycobacterium cultures of the aspiration specimen were all negative. TB quantiferon, polymerase chain reaction test and acid-fast bacilli staining were negative. On the other hand, blood calcium and angiotensin-converting enzyme level were within normal range. The chest X-ray did not show any hilar adenopathy or pulmonary parenchymal infiltrate. Either tuberculosis or sarcoidosis was excluded with these results. Initially, an infectious origin was suggested. She was empirically treated with antibiotics: pristinamycin (7 days), amoxicillin-clavulanic acid (10 days), and trimethoprim-sulfamethoxazole (2 months). Then, a treatment with colchicine 1mg/day was administered as the disease worsened with discharge and fistulation of the swelling at the biopsy sites. Spectrometry of a pus sample identified a germ called Corynebacterium kroppenstedtii. The other two bacteriological control samples were aseptic. The diagnosis of IGM associated with erythema nodosum was evocated. Daily prednisone 60 mg was started with a gradual taper 5 months. The evolution was rapidly favorable with complete regression of the breast swelling and erythema nodosum. No recurrence was reported within two years of follow-up.

madagascar, corticosteroid, erythema nodosum, granulomatous mastitis

PMC9358446_01

Female

A 20-year-old woman, with body weight 46 kg was diagnosed as having MDR-TB plus resistance to fluoroquinolone and was treated with linezolid-containing regimen (cycloserine 750 mg, clofazimine 100 mg, linezolid 600 mg (13 mg/kg body weight), bedaquiline 200 mg). She had no other disease and was not taking any other medication. Before starting MDR-TB treatment, her hemoglobin (Hb) level was 12.1 gr/dL, neutrophil and platelet count were 3450/ml and 298,000/ml respectively. She developed severe anemia (Hb level 5.5 g/dL) at 12th week of treatment, accompanied with declining neutrophil and platelet count (1570/ml and 254,000/ml, respectively). No other causes of anemia were found. She was hospitalized and had 4 packed red cell transfusion. Linezolid was stopped and delamanid 100 mg bid was started. Four weeks after linezolid was stopped, her Hb level was 12.7 gr/dL, neutrophil and platelet count were 2180 /ml and 280,000/ml, respectively. GDF-15 level was normal at baseline: 1189.52 pg/ml (normal 200 -1200 pg/ml), and markedly elevated to 4108.88 pg/ml at 2nd week of linezolid treatment.

anemia, case series, growth differentiation factor-15, linezolid, multi-drug resistant tuberculosis

PMC9358446_02

Male

A 66-year-old man, with body weight 40 kg was started on treatment for MDR-TB with the WHO recommended initial regimen (cycloserine 750 mg, levofloxacin 750 mg, clofazimine 100 mg, linezolid 450 mg (11 mg/kg body weight), bedaquiline 200 mg). He had diabetes mellitus treated with insulin. He had not taken any other medication. Before starting TB treatment, he already had low hemoglobin level (10 g/dL), normal neutrophil (6190/ml) and platelet (447,000/ml) count. He developed severe anemia (Hb level 5.7 g/dL) at the 8th week of treatment with neutrophil 1980/ml and platelet 241,000/ml. No other causes of anemia were found. He was hospitalized and received 3 packed red cell transfusion. Linezolid was stopped and changed with delamanid 100 mg bid. Four weeks after linezolid was stopped, his Hb level was 8.8 gr/dL, neutrophil and platelet count were 3030 /ml and 147,000/ml, respectively. Elevated GDF-15 level was detected before treatment: 11,634.4 pg/ml (normal 200-1200 pg/ml).

anemia, case series, growth differentiation factor-15, linezolid, multi-drug resistant tuberculosis

PMC9358446_03

Male

A 51-year-old man, with body weight 69 kg was diagnosed as having MDR-TB and was treated with linezolid-containing regimen (cycloserine 750 mg, levofloxacin 750 mg, clofazimine 100 mg, linezolid 600 mg (8 mg/kg body weight), bedaquiline 200 mg). He had diabetes mellitus, chronic kidney disease, and mass in urinary bladder. His blood sugar level was controlled by diet, he had not taken any other medication. Before starting TB treatment, his Hb level was 13 g/dL, neutrophil and platelet count was 7690 /ml and 490,000/ml, respectively. He developed moderate anemia (Hb level 9.6 g/dL) at 4th week of treatment with neutrophil 6560 /ml and platelet 543,000/ml. There was no other cause of anemia found. He was hospitalized and received 2 packed red cell transfusion. Linezolid was continued. Four week later, his Hb level was 11.4 gr/dL, neutrophil 7390 /ml and platelet 434,000/ml. GDF-15 level was markedly high at baseline: 12,105.28 pg/ml (normal 200-1200 pg/ml) and further increased to 27,450.88 pg/ml at the 2nd week of linezolid treatment. Hematology parameters over time after starting MDR-TB treatment in all three patients are depicted in Fig. 1.

anemia, case series, growth differentiation factor-15, linezolid, multi-drug resistant tuberculosis

PMC10435267_01

Male

A 67-year-old man was incidentally diagnosed with iCCA when he presented with gallstone pancreatitis in March 2020. There was no relevant medical or family history. He proceeded to have a left hemihepatectomy and cholecystectomy in April 2020; histology confirmed this was a complete resection of a pT2 NX R0 iCCA. This was not followed by adjuvant chemotherapy. He was diagnosed with metastatic CCA when MRI and CT imaging in October 2020 confirmed recurrence in the liver and lung. He was enrolled into a clinical trial in December 2020 to receive cisplatin plus gemcitabine, with or without immunotherapy. At the time of enrolment, the patients had PS 0 and normal hepatic and renal functions. Four months after enrolment, in April 2021, a CT scan showed stable lung disease but progressive hepatic disease. The patient's molecular profiling showed negative HER2 and NTRK mutations, intact mismatch repair and positive FGFR2 fusion. Thus, the patient started pemigatinib 13.5 mg once daily on days 1-14 of a 21-day cycle in July 2021, alongside supportive medications: topical emollient, antiemetic and antidiarrhoeal agents. Before the start of cycle 2 (29 July 2021), the serum phosphate level increased to 2.06 mmol/L and the patient presented with grade 1 dry mouth, mucosal dryness and diarrhoea. One month later, grade 1/2 toxicities were reported in the form of diarrhoea, abdominal pain, hair loss and nail discolouration. Therefore, the pemigatinib dose was reduced to 9 mg daily at cycle 3, significantly improving grade 2 diarrhoea and dry mouth. However, the nail changes persisted, and the patient was referred to a podiatrist. Aside from the observed toxicities, the patient showed partial response in the CT scan 2 months after treatment, and the serum CA19-9 decreased to a normal level. In November 2021, the patient suffered from nasal congestion and rash/erythema with induration over the right shin, which responded to topical steroids. Two weeks later, the patient reported abdominal discomfort and mild constipation. Thus, the decision was made to introduce a phosphate binder. A CT scan in January 2022 (6 months of treatment) showed stable disease, with a mild increase in the liver and pulmonary metastases. The serum CA19-9 increased to 161 U/mL. At the same time, the painless toenail changes were persistent, and the patient reported a painful heel during walking, suggestive of plantar fasciitis. Dermatological review noted diffuse destruction of the toenails with onycholysis and subungual haematoma; the fingernails presented with distal onycholysis only (Figure 2). Due to the persistent nail changes, a 2-week treatment break was decided, and pemigatinib was continued at a reduced dose of 9 mg. Following the re-initiation of pemigatinib, the patient reported improved plantar fasciitis; however, nail discolouration worsened. The serum CA19-9 has dropped to 74 from 240 U/mL. A CT scan on 28 February 2022 showed stable disease. One week after the CT scan, the patient reported grade 2/3 generalized abdominal pain and persistent nail discolouration. Thus, a 3-week break was commenced, leading to the resolution of abdominal pain but with ongoing nail changes. Pemigatinib 9 mg was restarted, and a CT scan in May 2022 showed stable pulmonary metastasis and a decrease in the size of hepatic metastases. Nonetheless, the patient reported heartburn and nizatidine was initiated. The patient then continued pemigatinib, with a supportive H2 blocker, an antidiarrhoeal agent and emollients. In August 2022, the patient showed improved nail changes with no signs of infection and stable grade 1 diarrhoea. A CT scan in September 2022 showed multifocal progression in the known hepatic and lung disease with new nodal and lung metastasis, and pemigatinib was discontinued, leading to a duration of benefit of 14 months. During pemigatinib therapy, the patient was able to maintain routine daily activities as most related toxicities were grade 1 or 2.

fgfr2 fusion, cholangiocarcinoma, metastatic disease, pemigatinib

PMC3702690_01

Female

A 47-year-old woman was admitted to the emergency service because of a motor vehicle crash in which she experienced head trauma. She was sitting in the front seat of the car and was not using a seatbelt. At the time of the accident, she lost consciousness for about 5 minutes. Her first neurological examination revealed non-specific findings. No gaze palsy was noted on initial assessment and diplopia was not present. She had a GCS of 15 points and showed several abrasions with scratches over the right forehead and tongue. Other systemic examinations were normal. Computerized tomography (CT) images of the skull and parenchyma were normal (Figure 1). Approximately 3 hours after the concussion, she had headache and diplopia. Neurologic examination revealed lateral gaze palsy of both eyes (Figures 2 and 3). The hypoglossal nerve was not initially evaluated because of stitches in her tongue.A follow-up neurologic examination revealed tongue deviation to the left side and CT imaging showed no newly developed abnormal lesions (Figure 4). In her cranial magnetic resonance imaging (MRI) she had contusion areas in the parietal and occipital lobes (Figure 5).The MRI angiography result was normal (Figure 6). Digital substraction angiography was performed after 1 month to exclude fistula formation and the result showed no abnormality. She was treated with methylprednisolone and was discharged with antibiotics and oral steroids prescribed for a period of 3 weeks. At 1-year follow-up, her sixth nerve palsy and hypoglossal nerve palsy was fully recovered (Figures 7 and 8).

abducens nerve injury, hypoglossal nerve injury, trauma

PMC5684593_01

Female

A 49-year-old woman patient diagnosed with HIV Type 1 infection and cluster of differentiation 4 (CD4) count of 482 presented to the Dermatology Department at Groote Schuur Hospital, Cape Town, South Africa, with a four-week history of multiple crusted plaques, nodules, and ulcers on her face, arms, and abdomen (Figures 1 and 2). She was on antiretroviral therapy. Her past medical history revealed red painful eyes six months prior to this presentation. She did not seek medical care for her eye condition. She had generalized lymphadenopathy. no alopecia, no palmar-plantar, and no mucosal lesions or lesions of lues maligna. There were no features suggestive of secondary syphilis such as a papulosquamous nonitchy eruption on her body. Neurological examination was normal. Ophthalmological examination revealed unilateral acute papillitis. The physical examination showed a well looking female patient with crusted plaques and nodules on face and abdomen and an ulcer on her forearm, hence double morphology (Figures 1 and 2). Our initial evaluation centered around lues maligna but this was excluded on the basis of the fact that lesions of lues maligna are usually multiple, well demarcated rupioid nodules and papules. A black eschar is sometimes observed on the lesions. Infections such as tuberculosis and deep fungal infections were also considered as atypical presentations are common in HIV infections. The patient was referred to an ophthalmologist and a diagnosis of papillitis was made. Rapid plasma reagin (RPR) test was positive (titer = 1 : 256, normal < 1 : 16). A diagnosis of tertiary syphilis with HIV coinfection was made. Tertiary syphilis diagnosis was made on the basis of the skin findings of gummas and papillitis, a manifestation of neurosyphilis. Lumbar puncture and skin biopsy were not done. She was treated with intravenous Penicillin G 5 MU IVI 6 hourly for 2 weeks. Healing occurred with atrophic scaring (Figures 3 and 4).

PMC1281282_02

Male

On 13 July 2002, a 62-year-old man was sent to the emergency room due to paraparesis after he received Chinese traditional chiropractic treatment from a nonprofessional. He was diagnosed with spondylitis with a T8 compression fracture and T9 myelopathy, suspected tuberculosis (TB) of the spine, and paraparesis and was transferred to a neurologic (internal medicine) ward in the evening. The next day he underwent surgery for total laminectomy (from T8 to T9) and hook system (from T6 to T11), and was sent to the surgical intensive care unit (SICU) for 5 days. On 18 July 2002, the patient was transferred to the neurologic surgery ward where the nurse worked. Because the patient was suspected of having TB of the spine, he underwent pleural and video-assisted thoracoscopic surgery (VATS) biopsy on 1 August. According to the nurse's observation, the patient was worried, anxious, and under a great deal of stress regarding his health because his income was the primary financial resource of his family. On 3 August, multiple pruritic rash and vesicles were found over the patient's abdomen and lower back flank area. Herpes zoster was confirmed by a dermatologic physician. During the patient's hospitalization in the neurologic surgery ward, the nurse attended the patient for several days (on 19-22 July, 29 July, 31 July-1 August, and 4-5 August 2002) before she resigned from the job on 12 August. Her regular nursing care tasks included measuring body temperature, blood pressure, and pulse; administering medicine; asking how the patient was feeling; and helping the patient to change his bed rest position. At the age of 5 years, the nurse had been infected with chickenpox by her kindergarten-age sister, who herself was previously infected by her kindergarten classmates. At that time, the nurse, her sister, and her brother had multiple chickenpox vesicles on their faces simultaneously. Because of her previous chickenpox history, it was supposed that the nurse was immune to the VZV; while caring for the patient, she did not wear gloves, a mask, or an isolation gown before the herpes zoster was confirmed. Because she had passed the admission examination for graduate study in a medical school, the nurse planned to resign her job to become a full-time student by 15 August. Before she resigned, she took a short vacation to her hometown in Ping-Tung County, in the south of Taiwan, on 6 August. However, on 8 August, she developed a high fever (39.5 C, 103.1 F), malaise, and headache. She went to a private clinic and was diagnosed with influenza by a physician in her hometown. The next day, in addition to the prodromal symptoms, pruritic rash started to appear on her face, neck, and trunk. She came back to the teaching general hospital in Taipei on 9 August and was diagnosed with varicella without mention of complication (ICD-9 code 052.9) by another dermatologic physician (not the herpes zoster patient's dermatologic physician). The nurse received treatment with Allegra (fexofenadine, 60 mg twice per day; Hoechst, Kansas City, MO, USA), chlorpheniramine (4 mg three time per day; Mine Ta Chemistry Pharmacy Co., Ltd., Tai Chung, Taiwan), and Scanol (acetominophen, 500 mg three times per day; Scanpharm, Birkerod, Denmark) for 14 days. Because her clinical symptoms were very clear, no laboratory confirmation testing was performed at that time. However, to confirm this second varicella episode before reporting this case, we invited the nurse to take serologic tests for varicella antibody on 4 April 2005. The results indicated that VZV-specific IgM was negative [< 1:20; Merifluor VZV IgM indirect fluorescent antibody, (IFA); Meridian Bioscience Inc., Cincinnati, OH, USA], but the VZV IgG was positive (1:80 on the basis of > 1:10, Merifluor VZV IgG IFA), with high sensitivity (93.9% for IgM and 100% for IgG) and high specificity (100% for both antibodies) according to the manufacturer's instructions. Negative specific serum IgM and positive specific serum IgG indicated a past VZV infection. Because varicella and herpes zoster both resulted from the same antigen, the VZV IgG-positive reaction was excluded from the herpes zoster. It was also excluded because the nurse did not get herpes zoster from the second episode of varicella on 9 August 2002 to 4 April 2005. The nurse is now convalescing.

PMC8486545_01

Male

A 33-year-old Native American man, a welder by profession, with a past medical history significant for alcohol use, hypertension, and asthma presented to the hospital with complaints of cough with occasional bloody sputum production. His cough started four days before presentation, was initially dry but progressively worsened, and became productive. It was also associated with dyspnea and orthopnea along with new-onset lower extremity edema. He further endorsed preceding nausea, vomiting, and diarrhea without abdominal pain, melena, or hematemesis. He reported an extensive history of alcohol consumption and had quit smoking 6 years ago. On physical examination, he appeared restless and his vitals comprised a temperature of 98.5 F, blood pressure 158/91 mm of Hg, respiratory rate 30 breaths/minute, pulse 116 beats/minute, oxygen saturation 96% on 2 liters of supplemental oxygen via a nasal cannula, weight 290 pounds, and a body mass index of 39.32. His pertinent laboratory findings included a white blood cell count of 16.3 K/uL, hemoglobin 8.6 g/dL, platelets 124,000 K/uL, potassium 3.0 mEq/L, sodium 125 mEq/L, magnesium 1.6 mg/dL, folate level 5.7 ng/mL, creatinine kinase 455 U/L, lactate dehydrogenase 310 U/L, albumin 2.9 g/dL, CRP 16.9 mg/L, lactic acid 3.1 mmol/L, procalcitonin 0.14 ng/mL, and D-dimer 10.56 ug/mL FEU. His ethanol level was 96.7 mg/dL, while liver function tests showed aspartate transaminase 132 U/L, alanine transaminase 33 U/L, and alkaline phosphatase 219 U/L. Testing for SARS-CoV-2, Human Immunodeficiency Virus (HIV), influenza, and methicillin-resistant Staphylococcus aureus (MRSA) nasal screen was negative. His computed tomographic angiogram of the chest (Figure 1) revealed bilateral infiltrates more extensive on the left as compared to the right and excluded pulmonary embolism. Ultrasound abdomen revealed hepatomegaly. An echocardiogram showed an ejection fraction of 65-70% with moderate left ventricular hypertrophy, left atrial enlargement, and right atrial dilation. He was started on empiric treatment with ceftriaxone 2 gm daily and doxycycline 100 mg twice a day for suspected bacterial pneumonia along with management of possible alcoholic hepatitis with thiamine and folic acid and Clinical Institute Withdrawal Assessment for Alcohol (CIWA) protocol. On day 2 of hospitalization, his hemoptysis and breathing deteriorated, and his white cell count rose further to 18.1 K/uL. His supplemental oxygen requirements increased, and chest X-ray (CXR) (Figure 2(a)) showed worsening left-sided infiltrates. Following this, the antibiotic regimen was broadened to cefepime 2 gm three times a day for 8 days and vancomycin dosed by the pharmacy for 5 days. Urine Legionella antigen, Streptococcus pneumoniae direct antigen, Aspergillus, Blastomyces, Coccidiodes, histoplasma antibodies, and repeat SARS-CoV-2 testing were all negative. Blood cultures and sputum cultures were obtained and were found to have no growth. Bronchoscopy was performed revealing DAH thought secondary to pulmonary edema. Intravenous (IV) steroids were started, and further infectious and autoimmune workup was undertaken. Bronchoalveolar lavage sampling was negative for acid-fast bacilli, Nocardia cultures, and CMV DNA. With the continued decline in respiratory function, he underwent endotracheal intubation. While on mechanical ventilation, aggressive diuresis was initiated for pulmonary edema. Thereafter, he was weaned off the ventilator and extubated within a week. His hemoptysis resolved, but he continued to cough with infrequent mucoid phlegm. Antibiotics were discontinued after ten days when he was clinically better, and repeat CXR exhibited slight improvement in left-sided infiltrates along with the resolution of his right lung consolidation. Steroids were transitioned from IV to oral prednisolone 40 mg daily for 26 days followed by a taper to cover for suspected alcoholic hepatitis. His mental function improved with alcohol withdrawal treatment and he became more alert and oriented. On further questioning, he recalled having exposure to sick kittens and mice few days before admission. He was tested for Hantavirus, Q fever, leptospirosis, and toxoplasmosis, and empiric treatment with doxycycline 100 mg twice a day was initiated for 3 weeks. TB testing (QuantiFERON, sputum acid-fast bacilli, and PPD) and antibodies for leptospirosis and Q fever were all negative. On day 18, the patient was hemodynamically stable with complete resolution of respiratory failure and was deemed stable for discharge. Four days after discharge, Hantavirus IgM returned positive with equivocal IgG. Retrospectively, his presentation correlated with HCPS. Upon follow-up in the clinic 10 days after discharge from the hospital, he reported improvement in cough and dyspnea. Outpatient CXR (Figure 2(b)) revealed mild improvement of left upper lobe consolidation.

PMC7783156_01

Male

The case participant is a 63-year-old male former Australian rules footballer, who played from the age of eight to retirement in his early 30s, including more than 200 professional games. He suffered several concussion injuries during his career (exact number unknown) including a period when he suffered three concussions in 4 weeks. He did not report any significant or ongoing cognitive or behavioral symptoms at the time of sustaining the concussion or at retirement. Following retirement from football, the participant worked in a coaching role. There was no history of exposure to other head impacts, no alcohol or drug abuse, and no family history of Alzheimer's disease (AD) or other dementia. In his mid-50s, the participant had a stroke, which presented with features including non-fluent dysphasia and facial droop. An MR brain scan noted a 10-mm left thalamic infarct. Resulting short-term memory impairment necessitated a change to a less demanding occupation and he remains employed as a factory worker. His family reported gradual deterioration in his short-term memory post-stroke and recent behavioral change. His presentation was complicated by severe deafness and reluctance to use a hearing aid. Neurological examination was normal other than a loss of sense of smell.

alzheimer's disease (ad), chronic traumatic encephalopathy (cte), positron emission tomography (pet), case report, tau

PMC7091521_01

Female

A 45-year-old woman, madam CB, was referred to our emergency unit on 22 July 2018. The patient was referred on account of eclampsia, acute kidney injury, and HELLP syndrome at 33 weeks gestation. The patient presented there with complaints of epigastric pain and blurred vision of a day's duration. She was apparently well until a day prior to presentation when she had the above complaints, which became associated with tonic clinic seizures at home with tongue bite; hence, she was rushed to the hospital. At the hospital, she had another episode of tonic clinic seizures. She was stabilized and referred to KATH for further management. The patient was given antihypertensives and anticonvulsant before referral. At KATH, the blood pressure was high with proteinuria of 3+; however, the SpO2 was 99% on room air. She looked very unwell, pale, and not jaundiced with good hydration. Her chest was clinically clear. She had epigastric pain. Symphysis-fundal height of 32 cm was consistent with the gestational age. Lie was longitudinal, and presentation was cephalic. Fetal heartbeat was present and normal. No contractions were felt. On pelvic examination, the vulva and vagina looked healthy. The cervical os was closed, and the cervix was 2 cm long, firm, and posterior. The patient had 500 mL of cola-like urine and bedside clotting of 15 min. Impression of eclampsia with HELLP syndrome with an unfavorable cervix was made. The patient had samples taken for FBC, BUE, creatinine, serum uric acid, and grouping and crossmatch for 4 units of whole blood and 8 units of FFP. She was then prepared for emergency CS after the bedside clotting was corrected with transfusion of 3 FFPs. Immediately postop, the patient was very stable with normal vital parameters. 4 h post-CS, the patient had abdominal distension was tympanic, severally pale, and jaundiced. The uterus was well contracted, and shifting dullness was negative. Her pulse was 116 with blood pressure of 164/112 mmHg. The patient had made 30 mL of cola-like urine in 4 hours. No bleeding per vaginam was noted. She was continued with the haemotransfusion and the FFP, but unfortunately, her condition did not improve and she ceased breathing. Cardiopulmonary resuscitation was attempted for over 30 min but was unsuccessful; hence, she was declared dead. Her labs came later, and liver indices were all markedly raised.

PMC3542310_01

Female

A 72-year-old woman was admitted to the hospital complaining of right upper quadrant pain. Initial abdominopelvic CT showed hepatic hilar obstruction due to cholangiocarcinoma, extending from hilum of extrahepatic bile duct to distal common bile duct. Elevated total bilirubin level (13.0 mg/dL) and direct bilirubin level (10.8 mg/dL) were found at admission. Alkaline phosphatase level (1189 IU/L) and gamma-glutamyl transpeptidase (229 mg/dL) were also elevated. Percutaneous transhepatic biliary drainage (PTBD) through the right intrahepatic bile duct (Fig. 1B-a) resulted from a Bismuth type II cholangiocarcinoma. We planned on the newly designed Y-shaped covered stent insertion on the fourth day after the initial drainage procedure, and performed another PTBD through the left intrahepatic bile duct (S3 duct) (Fig. 1B-b). Before inserting the Y-shaped biliary covered stent, the drainage catheters were removed and 8 Fr sheaths inserted over a 0.035-inch hydrophilic guide wire (Terumo, Tokyo, Japan) bilaterally. First, we inserted and located the main piece of stent into the common bile duct through left PTBD tract (Fig. 1C). The proximal end of the main piece stent (EGIS KEY-MB stent) (S&G Bio, Seoul, Korea) was located in the left intrahepatic bile duct (IHD) beyond the boundary of the hilar tumor (Fig. 1C, thick arrows). The short limb covered portion of the main piece stent was directed toward the left side of the common bile duct (Fig. 1C, thin arrows). To easily insert and deploy the contra-lateral long limb covered stent (EGIS KEY-CL stent) (S&G Bio, Seoul, Korea) without kinking its struts, the long limb covered stent of the main piece was not to be deployed (Fig. 1D, three thick arrows) until the contra-lateral long limb covered stent was completely deployed in an adequate position. After successful negotiation of a guide wire into the short limb covered stent of the main piece, a contra-lateral long limb covered stent was inserted through the right PTBD tract to connect this short limb covered stent of the main piece under the guidance of a 0.035-inch guide wire. After the confirmation that its proximal end was located in the right IHD beyond the boundary of the hilar tumor, we deployed the contra-lateral long limb covered (Fig. 1E). Finally, the long limb covered stent of the main piece was completely deployed. A 7 Fr drainage catheter was placed through the left IHD with its tip located in the common bile duct. To confirm the correct stent expansion and function, post-stenting cholangiography was performed through the drainage catheter just after the stent insertion (Fig. 1F) and 7 days later. Cholangiography showed good bilateral communication via completely expanded stents, and the drainage catheter was removed. On eighth day following the stent placement, total bilirubin and direct bilirubin levels decreased to 2.7 mg/dL and 2.2 mg/dL, respectively. They have not been elevated in the 12 months following the Y-shaped covered stent insertion (total bilirubin/direct bilirubin = 0.9/0.5 mg/dL).

biliary stent, bismuth type, cholangiocarcinoma, covered stent, percutaneous transhepatic biliary drainage

PMC8355958_01

Male

Case #1 is of a 16-year-old male with a history of attention-deficit disorder who presented to an outside pediatric emergency department after he experienced immediate right knee pain following a noncontact, twisting injury while participating in a football practice. At the outside emergency department, plain radiographs were obtained which demonstrated a pathologic fracture of the right distal femur (Figure 1). Prior to the injury, the patient denied having any night sweats or night pain but had noted vague knee pain which he attributed to a prior reported MCL injury. Given the benign appearance of the lesion, the fracture was definitively fixed using a lateral distal femoral locking (Figure 2). No curettage was performed. Approximately five months after surgery, the patient started experiencing increased pain around the knee which was initially attributed to hardware irritation. He continued to have pain, and a CT was ordered approximately nine months postoperatively to evaluate for union at the fracture site. The CT showed that all cortices had fully healed but the intramedullary lesion persisted. There were no hardware complications (Figure 3). 16 months postoperatively, he started to notice knee effusions after he had returned to playing football. Aspiration of the knee revealed a tense hemarthrosis. The hemarthrosis returned two days later, and a CT and MRI were obtained confirming a new hemarthrosis and a healed nonossifying fibroma (NOF) approximately 2.4 cm (width) by 2.1 cm (depth) and by 4.1 cm (length) proximal to the distal femoral. CT demonstrated an anterior cortical defect approximately 7 cm proximal to the distal femur (Figure 4). A second arthrocentesis was performed, yielding 30 mL of blood. Cell count, cultures, and crystals were unremarkable, and a coagulopathy workup was negative. Given his continued symptoms, the patient underwent a diagnostic arthroscopy, curettage, and bone grafting of the lesion. Arthroscopy showed persistent hemosiderin-tinged synovium throughout the knee with no evidence of screw penetration into the joint. However, the distal aspect of the plate was identified within the lateral gutter, and a sinus tract was discovered between the distal-most aspect of the NOF and the suprapatellar pouch. Specimen was collected for both frozen and permanent pathology, which was consistent with NOF (Figure 5). The sinus tract was resected, and careful closure of the capsule in the suprapatellar pouch was performed with absorbable suture. The lesion was then packed with cancellous allograft. He was last seen in clinic 6 weeks postoperatively, and he continued to do well with no return of symptoms, participating in activities as tolerated, with routine healing of the lesion (Figure 6). When he was contacted for permission to be included in this case study, 22 months following the last procedure, he had not had any recurrence of symptoms.

PMC10040642_01

Male

The patient was a 13-year-old Japanese boy, the first of three siblings from non-consanguineous parents. He had no history of statin exposure and no family history of neuromuscular disease. He was a basketball player and presented with progressive difficulties in shooting, running, and subsequently walking during the previous one month. Vital signs were normal (heart rate, 82 beats/min; respiratory rate, 15 breaths/min; blood pressure, 113/57 mmHg; body temperature, 36.5 C). Physical examination revealed grade 3/5 muscle weakness in the upper extremities and 4/5 in the lower extremities based on the Medical Research Council (MRC) scale (0-5). The patient also presented with generalized erythematous skin rash (Figure 1). Other general physical examination findings were unremarkable. Serum levels of CK (19,306 U/L), aldolase (257 U/L), aspartate aminotransferase (274 U/L), and lactate dehydrogenase (1,471 U/L) were all elevated. Magnetic resonance imaging detected signal hyperintensity on T2-weighted imaging and short tau inversion recovery imaging for muscles in the proximal upper and lower extremities (Figure 2). Muscle biopsy showed necrosis and regeneration of muscle fibers (Figure 3). Immunohistochemistry demonstrated overexpression of major histocompatibility complex class 1 and membrane attack complex (C5b-9) on the sarcolemma and granular sarcoplasmic expression of p62 (Figure 3). As measured by quantitative enzyme-linked immunosorbent assay (Cosmic Corporation, Tokyo, Japan), anti-HMGCR antibody level was 2.9 IU/ml (reference value <1.0 IU/ml), while negative results were obtained for anti-signal recognition particle antibody and other myositis-associated antibodies, including anti-Jo-1, anti-Mi-2, anti-MDA-5, and anti-TIF-1 gamma antibodies. The patient was subsequently diagnosed with anti-HMGCR myopathy. Based on the consensus statement on the initial treatment for anti-HMGCR myopathy from the 224th European Neuromuscular Centre International Workshop, intravenous methylprednisolone (1 g/day for 3 days) followed by oral prednisolone (1 mg/kg/day), monthly IVIg (2 g/kg/dose, three times), and oral methotrexate (0.3 mg/kg/week) was started 3 months after the first evaluation. MRC scale scores for the upper and lower extremities normalized (grade 5/5) and serum CK (201 U/L), aldolase (8 U/L), aspartate aminotransferase (16 U/L), and lactate dehydrogenase (280 U/L) levels were all decreased by 3 months after treatment initiation. The patient resumed playing basketball at the same level as that before the onset of anti-HMGCR myopathy. The patient has continued to receive methotrexate monotherapy and as of the time of writing, has remained relapse-free for 2 years.

autoimmune disease, creatine kinase, hydroxymethylglutaryl coa reductase, muscular disease, myositis

PMC9094363_01

Male

We report a case of HBSL in a 45-year old Han Chinese man of Sichuan Province. He had a history of normal birth and development of bilateral lower limb paralysis and delay in motor functions since 2 years of age. He complained of difficulty in walking, abnormal posture, and difficulty in standing after squatting down. By the age of 4 years, the patient could walk only with support, and by 5 years of age, he required support to stand as well. However, both the upper limbs had normal motor and cognitive functions. The patient did not receive any treatment due to poor economic background leading to a delay in diagnosis and treatment. He came for medical advice 1-year back due to progressive weakening in both upper limbs. At the time of consultation, the patient was unable to stand up, faced difficulty in raising upper limbs, and his cognitive function was deranged. On physical examination, findings were muscle strength grade 3 in both the upper limbs, hypermyotonia, hyperreflexia in bilateral upper and lower limbs (+++), positive bilateral Hoffman sign, higher muscle tension in both lower limbs, and a positive bilateral Babinski sign. Laboratory examination revealed plasma thrombin time 15.8 s, rheumatoid factor 21 IU/ml, and blood transferrin level 1.79 g/L. Routine blood test, urine test, and stool test were within normal limits. Liver and kidney function tests, electrolytes, tumor marker, and autoimmune antibody profile revealed no abnormality. An electrocardiogram showed a sinus heart rate of 69 beats per minute. The heart ultrasound showed no significant abnormalities in cardiac structure and blood flow. The electromyogram demonstrated normal right anterior tibial nerve insertion potential, incomplete light and strong contraction, the right dorsal inter bone muscle and bilateral medial femoral myoneurogenic injury, and myogenic damage. Multifocal lesions were detected on MRI by a decreased signal on the T1 sequence, increased signal intensity on the T2/FLAIR, and diffusion-weighted imaging (DWI) sequence showed a of the bilateral basal, centrum ovale, frontal lobe, and parietal lobe, and increased signal on the T2 sequence showed a of ganglia cervical cord (Figure 1). Whole-exome sequencing analysis was performed using whole-exome capture with NimbleGen2.0, detecting the distribution and concentration of qPCR amplified libraries by AgilentBioanalyzer2100 and Hiseq2500 sequencing. Variant annotation was performed using the PolyPhen-2.2.2 software, ANNOVAR software, HGMD, dbSNP, and 1,000 genome database. Mutations in DARS1 detected were, c.1363T > C (p.Y455H) (of maternal origin) and c.821C > G (p.A274G). Moreover, his elder brothers and sister's mutations in DARS1 detected were c.1363T > C (p.Y455H) and c.821C > G (p.A274G). And his mother's mutations in DARS1 were detected, namely, c.1363T > C (p.Y455H). The two elder brothers and sister of the proband developed weakness of lower limbs and walking unstable, when they were teenagers. The mother of proband has no obvious clinical symptoms at present, but it couldn not rule out the possibility she has no clinical symptoms in the future. (Figure 2). The mutations in DARS1 of the proband and his sibings were c.1363T > C (p.Y455H) (of maternal origin) and c.821C > G (p.A274G) (of paternal origin), and his father died when he was 12 and his gene could not be detected. We speculated that the cause of his father's death was gene mutation (Figure 2; Table 1). The mutations are termed as "pathogenic" and "likely pathogenic" according to the American College of Medical Genetics and Genomics (ACMG) guidelines, and a diagnosis of HBSL was made. The c.1363T > C (p.Y455H) gene was obtained from his mother. Since HBSL is characterized by hypomyelination, the treatment is essential to promote myelin repair. The patient was prescribed vitamin B1 (Yangzhou Eddie Pharmaceutical Co., Ltd.) 10 mg orally three times a day, methylcobalamin tablets (Wei Material, China Pharmaceutical Co., Ltd.) 0.5 mg three times a day, and cytophosphate choline sodium tablets (Sichuan Zitonggong Pharmaceutical Co., Ltd.) 0.2 g three times a day for a year. On a follow-up visit after 1 year, the patient could lift heavy weight and ambulate with the support of crutches.

dars1, hbsl, case reprot, mutation, posterior leukoencephalopathy sgndrome

PMC4602947_01

Male

A 63-year-old Japanese man with no symptoms had a positive fecal occult blood test. His past medical history included a duodenal ulcer at 50 years of age. The colonoscopy revealed, in the observation range, many scars caused by inflammation in the cecum and ascending colon, an intestinal stricture caused by inflammatory polyps in the transverse colon (Figure 1A-D), loss of both visible vascular patterns and haustra in the descending colon (Figure 1E), and normal mucosa in the sigmoid colon (Figure 1F), rectum, and ileum. Examination of biopsies from each segment of colon (including even specimens from normal mucosa) revealed chronic colitis accompanied by IS, as evidenced by basophilic fringes on the luminal surface of the intestinal mucosa and infiltration of lymphocytes and eosinophils in subepithelial lesions (Figure 2A). There were no obvious dysplastic changes (Figure 2B). Abdominal computed tomography (CT) revealed wall thickening in the transverse colon around the hepatic flexure (Figure 3A). The upper endoscopy and enteroscopy findings were within normal limits. Laboratory data, including carcinoembryonic antigen, carbohydrate antigen 19-9, interferon-gamma release assay (IGRA), purified protein derivative skin test, Entamoeba histolytica antibody, human immunodeficiency virus antibody, and fecal examinations, including culture and polymerase chain reaction for Mycobacterium tuberculosis, revealed no remarkable findings. Hence, his condition was diagnosed as chronic colitis associated with IS. Metronidazole (MNZ) 1500 mg/d for 14 days was initiated to treat the IS. Although spirochetes were eliminated in pathological examinations, MNZ was not effective for the intestinal stricture of the transverse colon. We performed colonoscopy 4 times for 20 months since the fecal occult blood test was positive and each biopsy indicated colitis but no obvious malignancy (Figure 2C, Table 1). The patient was admitted to our hospital with an acute abdomen 20 months after the initial presentation. He had urgent abdominal pain, constipation, and fever. Abdominal CT revealed exacerbation of the intestinal stricture in the transverse colon around the hepatic flexure (Figure 3B) and dilatation of the ascending colon with extraintestinal fluid (Figure 3C). We strongly suspected intestinal perforation due to obstruction. Subtotal colectomy and ileostomy were performed and the symptoms resolved. Histopathological examination of the specimens revealed MC that had infiltrated into the muscularis propia and subserous layers of the visceral peritoneum, purulent peritonitis due to perforation within the tumor and lymph node metastasis (Figure 4). The final histopathological diagnosis was a pT4a (invasion of serosa of peritoneum), pN1 (1/12), Ly0, V0, M0, and R0 tumor, corresponding to the Union for International Cancer Control IIIB classification. An immunohistochemical stain for DNA MMR proteins, including MLH1, MSH2, PMS2, and MSH6, revealed no lack of these expressions (Figure 5). Intensified adjuvant chemotherapy according to the Xeloda (capecitabine) and oxaliplatin schema was initiated. Currently, after 14 months of follow-up, the patient is without detectable tumor recurrence, as shown by abdominal CT scan and ultrasound examination (Table 1).

PMC6770300_01

Female

A 64-year-old female underwent haploidentical allogeneic HSCT for diagnosis of acute myeloid leukemia secondary to myelodysplastic syndrome in September 2016. A haploidentical son, 41 years old, 0 Rh positive, EBV, CMV, and toxoplasma IgG positive, was selected as the donor because of the lack of a well-matched unrelated stem cell donor according to our transplant policy. The Valencia schedule, consisting of a combination of reduced dose of thiotepa, Busilvex, and fludarabine, was used as a conditioning regimen, while the association of cyclosporine (0.75 mg/Kg/12 h continuous infusion from day -7, increased from day -1 to 1.5 mg/Kg/12 h continuous infusion), a short course of methotrexate (15 mg/mq on day 1 and 10 mg/mq on day 3-6 and 11), rabbit anti-thymocyte globulin (ATG) (5 mg/Kg/die from day -4 to day -1), basiliximab (20 mg on day 0 and day +4), and mycophenolic acid (15 mg/Kg twice daily) was administered as GVHD prophylaxis. On day +100 after transplant, she developed acute gastrointestinal (GI) tract (stage 1, grade 2) GVHD successfully treated with steroids. Transplant-related complications due to the consequent use of a high-dose steroid for long time for GVHD included multiple episodes of reactivation of cytomegalovirus responded to antiviral therapy, sarcopenia, and fracture of the head of the femur surgically resolved. On day +320 after transplant, the patient presented with nausea, vomiting, nystagmus, diplopia, and severe cutaneous purpura. A CT scan of the head showed a right multicystic cerebellar mass with perilesional edema compressing the fourth ventricle, also confirmed by brain MRI. As the lesions were not previously reported, we ruled out congenital abnormalities such as cavernous malformations. Since other differential diagnosis, including infectious (tuberculotic, echinococcal, and toxoplasmotic cysts) and neoplastic diseases, required a histological assessment, we proceeded to a surgical excision of one of the neuroradiological lesions. An attempted biopsy of the cystic lesions, through suboccipital craniotomy, failed due to moderate bleeding during surgery. Histologic findings showed normal cerebellar tissue with polymorphonuclear leukocytes. Although the available specimen was not sufficient for all diagnostic tests, no neoplastic cells or fungal hyphae were seen. The fundus oculi assessment did not show cystis. Moreover, the quantiferon and TB skin test (or PPD test) were negative. Although prompt empiric antibiotic combination of meropenem and clindamycin was started, clinical and neuroradiological response was not achieved. High-dose intravenous trimethoprim-sulfamethoxazole for a suspicious cerebral toxoplasmosis, due to donor and patient IgG positivity before HSCT, was given after 20 days of antibiotic therapy. After two weeks of this therapy, continued clinical symptoms and MRI of the brain showed worsening of multicystic lesions with perifocal edema and initial cerebellar herniation. The patient also developed an intention tremor, bilateral hypoacusia, and severe haematological toxicity. In absence of clinical and radiological improvement and taking into account the patient's history of living in countryside, we applied the revised diagnostic criteria for Taenia solium infection and discovered that our patient presented a definitive diagnosis of NCC due to the neuroimaging presence of cystic lesions without a discernible scolex and enhancing lesion plus previous household contact with T. solium and neurological clinical manifestations of NCC. Moreover, in this case we documented the resolution of cystic lesions after cysticidal drug therapy (Figure 1), as confirmative criterion. However, no cystic lesions were found in muscles, and the IgG Elisa test in blood and 3 consecutive stool samples were negative for T. Solium. The patient started empiric antiparasitic treatment with albendazole (400 mg PO BID) plus intravenous administration of dexamethasone (4 mg/day). Lumbar puncture was not performed due to high risk of hernia wedging and MRI signs of hydrocephalus. After 14 days, brain MRI control showed disappearance of some of the cystic lesions in the right cerebellar hemisphere and the reduction in size of some others. Patient was released from the hospital with no neurological symptoms, continuing albendazole therapy for four months.

PMC7428087_01

Male

The first confirmed COVID-19 case was a 35-year-old man who was in charge of transferring patients inside our hospital between February 2 and 17. On February 17, 2020, he visited the clinic due to a one-week history of fever, cough, and myalgia. Although he had no history of travel or close contact with confirmed COVID-19 cases, chest X-ray showed ground-glass opacities in both lower lobes. Considering the possibility of COVID-19, RT-PCR confirmation testing was performed on February 20, 2020. After SARS-CoV-2 infection was confirmed, the Seoul city government announced the closure of the hospital on February 21, 2020, to prevent a healthcare-associated outbreak. Outpatient clinics and the emergency room were also closed, and new patient admissions were stopped. Individuals inside the hospital who had contact history, fever, or respiratory symptoms, were closely monitored.

PMC5684436_02

Female

This was 76 year old lady of Pakistani origin who worked as an electrician exposing herself to silica. The patient was admitted to hospital with shortness of breath, cough and fever over the last few days. The cough was non-productive, however as she was coughing a lot she developed chest pain. There was no history of a rash, coagulopathy or arthritis. A chest radiograph (CXR) was performed which showed pulmonary congestion and right basal consolidation and was treated as an infective condition. The patient was discharged four days later with antibiotics and diuretics, with the plan to have a high resolution computed tomography (HRCT) scan, outpatient spirometry, followed by a chest clinic review as there seemed to be an underlying chronic lung pathology which needed to be investigated. However, the patient was then readmitted three days later due to the worsening of her symptoms. A computerised tomography pulmonary angiography (CTPA) was performed which showed extensive peripheral opacities sparing the peri-hilar region and apico-basal gradient pattern. The findings were suggestive of eosinophilic lung disease or nonspecific interstitial pneumonia. The patient carried out electronic soldering as her profession. During her work she was exposed to silica. She was also a passive smoker as her husband whom she lived with, was a smoker. The bronchoalveolar lavage (BAL) from the right lower lobe laboratory analysis showed approximately 10mls of cloudy pink fluid. Microscopy result was benign respiratory epithelial cells, alveolar macrophages and scattered mixed inflammatory cells present. No malignant cells were seen. It is known in interstitial pneumonitis the diffuse alveolar damage is commonly caused by fibroblast invasion into the tissue and proliferation. TB culture and gram stain bacteriology from the BAL were also negative. However candida albicans was noted on mycology, which was thought to be likely a contaminant cause. Blood cultures and virology screen were also negative. However her (ANCA) perinuclear was mildly positive. Her serum ACE was 50u/l and IgE was elevated (512u/l). These results may occur in treated, inactive or relapsing microscopic polyangiitis (including its renal-limited variant), granulomatosis with polyangiitis and Churg-Strauss syndrome. Patients with systemic vasculitis in whom ANCA recur are more likely to relapse. It is also common in inflammatory bowel disease and other autoimmune diseases where its clinical significance is unclear. If ANA is present this may be a false positive result. White cell count (WCC) 15 C-Reactive Protein (CRP) 77 7 days later WCC 8CRP 29 34 days later WCC 18 CRP 42 Bloods: on admission: The echocardiogram revealed pulmonary hypertension. Autoimmune serology were sent (antinuclear antibodies, antineutrophil cytoplasmic antibodies, extractable nuclear antigen antibodies, IgE antibodies, aspergillus antibodies and precipitins, anti Ro, anti La, anti ribonucleoprotein, anti Smith, anti Jo1 and anti SCL-70 antibodies including anti nuclear antibody (liver) gastric parietal cell IgG antibody, smooth muscle IgG antibody, liver/kidney microsomal antibody and mitochondrial antibody) were all negative. A bronchoscopy was performed to exclude TB and fungal infections. Imaging: The extensive consolidation in the right mid zone and left base has increased since the previous film. There is loss of volume in both lungs. Atypical infection as well as acute, rapidly progressive pulmonary fibrosing alveolitis should be suspected. The extensive parenchymal changes in both lungs are noted. No significant difference is identified compared to a previous film. CXR Poor inspiratory effort with small volume lungs. Extensive interstitial and airspace shadowing in the right mid zone and both lung bases. There is a small left pleural effusion. CXR Suboptimal aspiration with small volume lungs. There is consolidation in the right mid zone and left lower lobe. Small bilateral pleural effusions are present. A background of bilateral pulmonary congestion is present. CT Pulmonary Angiogram: CT imaging revealed: Presence of extensive peripheral opacities of the lungs which are sparing the peri-hilar regions and show an apico-basal gradient pattern. The findings could be due to eosinophilic lung disease or non specific interstitial pneumonia (NSIP). Small bilateral pleural effusions seen. Reactive, borderline mediastinal lymph nodes seen. The heart size is normal and there is no pericardial effusion. The aorta and great vessels are normal in calibre. The central pulmonary arteries are patent with no evidence of embolus. The trachea and mainstem bronchi are patent. The oesophagus is normal in course and calibre. There is no pneumothorax. Scans through the upper abdomen are unremarkable. The osseous structures in the chest are intact. In comparison to CT PA of 37days prior there has been worsening of widespread patchy consolidation. There are multifocal diffuse areas of consolidations bilaterally, involving all lobes. Air bronchograms are present. No pulmonary embolism. No pleural/pericardial effusion. No enlarged mediastinal or axillary lymph nodes. Small mediastinal lymph nodes noted. These radiological findings were suggestive for eosinophilic lung disease or non-specific interstitial pneumonia (NSIP) as reviewed at the Lung Multidisciplinary Team meeting. Differential diagnoses included infective causes, aspiration, drugs, autoimmune conditions particularly vasculitis such as Churg-Strauss syndrome and acute interstitial lung disease. Radiological differential diagnosis included acute respiratory distress syndrome (ARDS), Churg Strauss and cryptogenic organizing pneumonia (COP). On admission the patient was given a one week course of Co-amoxiclav which did not seem to improve the patient's cough. Therefore the patient was booked for follow-up in respiratory clinic with HRCT and outpatient spirometry. One month later the patient returned to hospital with worsening of symptoms and was given two week course of intravenous (IV) Tazocin and Meropenem. The patient was discussed with the center of excellence in interstitial lung disease, who advised on stopping any possible triggers for interstitial pneumonitis (Aspirin and Omeprazole were the only possible medications reported in the literature to trigger Acute Interstitial Pneumonia (AIP) and adding Linezolid and Vancomycin for possible resistant organisms. Following the interventions above the patient received a pulse therapy with methyl-Prednisolone of 1g IV for three consecutive days, followed by hydrocortisone IV and a prolonged course of Corticosteroids (Prednisolone 60mg daily, weaned to 30mg daily over a three month period). The patient's oxygen requirements reduced and she made good progress with the physiotherapists. She was seen in the oxygen clinic three weeks after discharge requiring only 3L/min of oxygen 24 hours a day saturating at 98%. Another key element of the treatment consisted of high flow humidified heated oxygen therapy delivered via optiflow. This has helped prevent admission to ITU for intubation with a positive effect on acute hypoxemic respiratory failure and secretions management. Optiflow was delivered on the respiratory ward at a 60% Fio2, with a 60L/min flow and the patient's temperature was maintained at 37 celsius. Oxygen requirement improved over the 6 weeks admission to hospital, requiring 3L/min long term oxygen therapy (LTOT) on discharge. She had a further sleep study on 2L/min oxygen and was advised to continue Prednisolone 30mg daily for a further three months.

PMC10010164_01

Male

A 61-year-old man was admitted to our hospital in May 2022 for three progressively enlarging masses in the left groin area and head, along with redness and swelling of the left thigh for more than half a year. He had a history of a major gastrectomy in 2015 after being diagnosed with gastric carcinoma. The patient was diagnosed with a 2.0x1.5x1.0cm tumor at the angle of stomach, and treated with Billroth II distal gastrectomy accompanied with D2 lymph node dissection. The postoperative histopathology of the primary lesion was mixed invasive adenocarcinoma, of which signet-ring cell carcinoma accounted for 80%, and tubular adenocarcinoma accounted for 20% ( Figure 1 ). The pathological stage was pT1N3M0. So, the patient received two cycles of oxaliplatin and tegafur chemotherapy, which was discontinued due to the inability to tolerate the side effects of chemotherapy. No tumor recurrence was found in the annual gastroscopy and CT-scan for 4 years after the operation; then, no follow-up was performed due to the COVID-19 epidemic. However, after 6 years, the patient developed a beaded nodular tumor in the left groin area and two fleshy nodules on the scalp, accompanied by redness and swelling from the upper left thigh to the groin area; there was no obvious fever or pain. This patient was diagnosed with "lymphangitis of lower limbs" in several major hospitals and was prescribed anti-inflammatory and detumescence treatment. After repeated treatment, the tumor in the left groin area and scalp gradually increased, and the skin of the left lower extremity was red, swollen, and scleroderma-like. Finally, he came to our hospital for treatment. A physical examination revealed moderate pitting edema of the left lower extremity, redness and swelling of the thigh with scleroderma-like changes, bead-like nodules of about 5*20cm in the groin area ( Figure 2A ), and two fleshy masses of about 3*3cm in size on the scalp ( Figures 2B, C ). The laboratory examinations showed that the blood routine, procalcitonin, liver, and kidney function were not abnormal, and the tumor markers carbohydrate antigen 72-4 and CA125 were elevated. A skin biopsy was performed on the groin mass, and the pathology showed metastatic poorly differentiated carcinoma, some of which were signet-ring cell carcinoma; immunohistochemical staining showed: PCK(+), CK7(+), CK20(-), CDX2(+), SATB2(-), and HER2(0) ( Figure 3 ). A whole-body PET-CT examination showed multiple humus-like hypodense nodules on the skin surface from the left groin to the thigh, secondary lymphedema, and slightly increased metabolic diffusion ( Figure 4A ). There was also localized thickening of the skin on the top of the left head and back of the neck, and slightly increased metabolism. The above suggested the possibility of malignant tumor metastatic lesions ( Figure 4B ). After the diagnosis was confirmed, the patient was transferred to the oncology department for chemotherapy of Nivolumab combined with SOX. Four times of chemotherapy had been performed, and the efficacy was evaluated as reduced SD. Due to the COVID-2019 epidemic, the patient did not come to our hospital for subsequent chemotherapy treatment as planned.

case report, cutaneous metastases, late recurrence, post operative metastasis, signet-ring cell gastric carcinoma

PMC5875111_01

Male

A 28-year-old man, with history of chronic alcohol abuse was found unconscious, with approximately 24 h after a traumatic brain injury (TBI) of unknown mechanism. He was admitted to our hospital for neurologic assessment and management. As recommended by the American College of Surgeons, his treatment followed the Advanced Trauma Life Support Management of severe brain injury protocol. A neurological examination revealed a Glasgow Coma Scale score of 6 and left anisocoria. He underwent brain computerized tomography (CT) that showed left hemispheric swelling associated with a temporo-parietal linear fracture and an acute subdural hemorrhage. He was immediately transferred to the operating room and, after balanced standard general anesthesia, he received a left question mark incision and a fronto-temporo-parietal craniectomy. After a durotomy and acute subdural drainage, he underwent dura mater reconstruction using galea aponeurotica. After standard subcutaneous tissue and skin closures, the extracted bone flap was bisected via osteotomy and both parts were subcutaneously stored in his left abdomen. Immediately after the procedure, the patient underwent postoperative CT scanning before his intensive care unit (ICU) admission. This revealed an acute epidural hematoma, so he was returned to operating room for further neurosurgery. After standard balanced general anesthesia, the question mark incision was reopened and the hematoma was removed. No active bleeding site was identified. After careful hemostasis, the skin flap was sutured shut, and the patient was transferred to the ICU. Because the patient presented diffuse brain edema, he was postoperatively sedated for 2 days, at which point CT scanning confirmed that his condition had improved. However, he was mildly sedated during the time of extubation. He developed pneumonia due mechanical ventilation, so he was tracheostomized and discharged from ICU without mechanical ventilation. Seven days before his hospital discharge, his tracheostomy cannula was withdrawn. The patient underwent repeated neurological examinations in the ICU. His pupils were anisocoric throughout his hospitalization. His Glasgow Scale score improved to 10T in the ICU and progressed until 15 after his ICU discharge. No motor deficits were identified at discharge. At his hospital discharge, which happened 33 days after the first procedure, he was orientated and alert but still had a left third cranial nerve deficit. One hundred and four days after craniectomy, the patient underwent a cranioplasty with his two abdominally stored autologous bone flaps. His head was positioned in a horseshoe-shaped restraint and the question mark incision was antiseptically reopened. A dissection was made between the galea and the dura mater to isolate the craniectomy's border. The abdominal incision was reopened to withdraw the bone flaps. During evaluation, signs of bone resorption were detected at the bone flaps temporal parts, but no corrections were made due to the poor esthetic results typically obtained from acrylic mold. Figure 1 shows the result obtained immediately after the cranioplasty. No adverse events were identified, though the patient received prophylactic cefuroxime for 48 h. Ten months after the craniectomy and 7 months after the cranioplasty, the patient returned to the trauma clinic with secondary bone defects related to near complete. It reached almost 95% of bone flap resorption, as proven in CT scan in Figures 2 and 3. External results can be observed in Figures 4 and 5. The patient is waiting for secondary cranioplasty with allogenic material and has made a seemly good neurological recovery considering the primary situation he had score 6 in Glasgow Outcome Scale - Extended.

autologous bone flap, cranioplasty, decompressive craniectomy, resorption

PMC8016374_02

Unknown

An epidemiological assessment during 2007 to 2010 in Rasht, north of Iran on burn patients hospitalized in Velayat Hospital included the total body surface area (TBSA) without reporting LA50 for those patients demonstrating a high prevalence of burn injuries in Iran that requires an increase in knowledge of the society as well as adhering to safety procedures both at home and workplace. In Imam Khomeini Hospital in Kermanashah, Western Iran during 2011-2012; LA50 was reported 50.82% in hospitalized patients. LA50 in burn injuries in Tehran, Iran, among 28690 burn patients from 3 months old to 93 yr old was shown to be 64.7%. We aimed to determine the epidemiology and LA50 in burn children in Ghotbedin-Shirazi and Amiralmomenin burn hospitals in Shiraz, southern Iran.

burn, children, epidemiology, iran, la50

PMC6149979_01

Female

A 67-year-old female former smoker was diagnosed with adenocarcinoma on the basis of pathological examination of transbronchial biopsy specimens. Distant metastases were not detected by the whole-body assessment. She underwent a right upper lobectomy with systematic lymph node dissection for lung adenocarcinoma (pT2aN0M0 stage IB: 7th edition of UICC TNM staging). Two years after the surgery, she developed numbness in both feet and was admitted to the emergency room. Spine MRI and chest computed tomography (CT) showed obvious nerve compression due to intradural extramedullary spinal metastasis, suggesting recurrence of her lung cancer. She underwent emergency palliative laminectomy decompression surgery. The pathological features and molecular profiles of the resected intradural extramedullary spinal tumor were reviewed. We diagnosed metastasis from lung adenocarcinoma; neither a mutated EGFR gene nor an ALK fusion gene was detected. Immunohistochemistry revealed high expression of PD-L1 showing a tumor proportion score of 50%-74% on the tumor cell membrane. One month after the palliative surgery, the patient's performance status improved from 3 to 1. However, as left pleural effusion, left hilar lymphadenopathy, and left lower tumor progressed (Figure 1), pembrolizumab treatment (200 mg/day) was initiated. After four cycles of pembrolizumab treatment, she did not have any respiratory symptoms, including coughing, hemoptysis, and dyspnea. However, chest X-ray revealed ground-glass opacities (GGOs) and consolidation in both the lungs. Chest CT showed GGOs and consolidation in both the lungs around the bronchial vascular bundles, along with a crazy-paving pattern (Figure 2A-C). A hematological examination showed increased inflammatory response (white blood cells 8,400/muL and serum C-reactive protein 4.7 mg/dL) and anemia (serum hemoglobin of 9.7 g/dL). Although KL-6 was not high (380 U/mL), SP-D was increased (351 ng/mL). The patient's serum antibody titers against Mycoplasma pneumoniae and Chlamydia pneumoniae were not elevated. The patient's urine was negative for pneumococcal and Legionella pneumophila serotype 1 antigens. Serologic data revealed no abnormal findings suggestive of collagen vascular diseases, including anti-neutrophil cytoplasmic antibody (ANCA), and no microorganisms grew on a sputum culture. Fiberoptic bronchoscopy was performed. Bronchoalveolar lavage (BAL) fluid from the right lower lobe gradually became bloody (Figure 3) with 45% lymphocytes (24.0% CD4, 71.4% CD8), 40% macrophages, 15% neutrophils, and 0% eosinophil. No microorganisms grew on a BAL fluid culture, and no evidence of malignancy was apparent. A transbronchial lung biopsy (TBLB) specimen obtained from the right lower lobe showed thickening of the alveolar walls with myxofibrous and lymphocytic infiltration changes (Figure 4). Although we could not find hemosiderin-laden macrophages in the TBLB specimens, agglutination of red blood cells with focal coagulate change was observed in the air spaces of the alveoli. We diagnosed pembrolizumab-induced ILD with alveolar hemorrhage. After fiberoptic bronchoscopy, oxygen desaturation was found, and oral prednisolone was started at 1.0 mg/kg/day for 2 weeks (initial dose: 40 mg/day) and then the dose was gradually decreased by 5 mg/day every week until reaching a dose of 20 mg/day. The patient's radiographic abnormal findings resolved rapidly (Figure 5), and oral prednisolone was tapered and then discontinued 3 months later without a recurrence of pneumonitis. The patient showed partial responses to pembrolizumab treatment; however, we did not try a challenge readministration of pembrolizumab. Written informed consent was obtained from the patient for publication of this case report and accompanying images.

pd-1, alveolar hemorrhage, pembrolizumab, pneumonitis

Computed tomography of the chest before treatment of pembrolizumab. Left pleural effusion, left hilar lymphadenopathy, and left lower tumor were observed (A and B).

PMC6149979_01

Female

A 67-year-old female former smoker was diagnosed with adenocarcinoma on the basis of pathological examination of transbronchial biopsy specimens. Distant metastases were not detected by the whole-body assessment. She underwent a right upper lobectomy with systematic lymph node dissection for lung adenocarcinoma (pT2aN0M0 stage IB: 7th edition of UICC TNM staging). Two years after the surgery, she developed numbness in both feet and was admitted to the emergency room. Spine MRI and chest computed tomography (CT) showed obvious nerve compression due to intradural extramedullary spinal metastasis, suggesting recurrence of her lung cancer. She underwent emergency palliative laminectomy decompression surgery. The pathological features and molecular profiles of the resected intradural extramedullary spinal tumor were reviewed. We diagnosed metastasis from lung adenocarcinoma; neither a mutated EGFR gene nor an ALK fusion gene was detected. Immunohistochemistry revealed high expression of PD-L1 showing a tumor proportion score of 50%-74% on the tumor cell membrane. One month after the palliative surgery, the patient's performance status improved from 3 to 1. However, as left pleural effusion, left hilar lymphadenopathy, and left lower tumor progressed (Figure 1), pembrolizumab treatment (200 mg/day) was initiated. After four cycles of pembrolizumab treatment, she did not have any respiratory symptoms, including coughing, hemoptysis, and dyspnea. However, chest X-ray revealed ground-glass opacities (GGOs) and consolidation in both the lungs. Chest CT showed GGOs and consolidation in both the lungs around the bronchial vascular bundles, along with a crazy-paving pattern (Figure 2A-C). A hematological examination showed increased inflammatory response (white blood cells 8,400/muL and serum C-reactive protein 4.7 mg/dL) and anemia (serum hemoglobin of 9.7 g/dL). Although KL-6 was not high (380 U/mL), SP-D was increased (351 ng/mL). The patient's serum antibody titers against Mycoplasma pneumoniae and Chlamydia pneumoniae were not elevated. The patient's urine was negative for pneumococcal and Legionella pneumophila serotype 1 antigens. Serologic data revealed no abnormal findings suggestive of collagen vascular diseases, including anti-neutrophil cytoplasmic antibody (ANCA), and no microorganisms grew on a sputum culture. Fiberoptic bronchoscopy was performed. Bronchoalveolar lavage (BAL) fluid from the right lower lobe gradually became bloody (Figure 3) with 45% lymphocytes (24.0% CD4, 71.4% CD8), 40% macrophages, 15% neutrophils, and 0% eosinophil. No microorganisms grew on a BAL fluid culture, and no evidence of malignancy was apparent. A transbronchial lung biopsy (TBLB) specimen obtained from the right lower lobe showed thickening of the alveolar walls with myxofibrous and lymphocytic infiltration changes (Figure 4). Although we could not find hemosiderin-laden macrophages in the TBLB specimens, agglutination of red blood cells with focal coagulate change was observed in the air spaces of the alveoli. We diagnosed pembrolizumab-induced ILD with alveolar hemorrhage. After fiberoptic bronchoscopy, oxygen desaturation was found, and oral prednisolone was started at 1.0 mg/kg/day for 2 weeks (initial dose: 40 mg/day) and then the dose was gradually decreased by 5 mg/day every week until reaching a dose of 20 mg/day. The patient's radiographic abnormal findings resolved rapidly (Figure 5), and oral prednisolone was tapered and then discontinued 3 months later without a recurrence of pneumonitis. The patient showed partial responses to pembrolizumab treatment; however, we did not try a challenge readministration of pembrolizumab. Written informed consent was obtained from the patient for publication of this case report and accompanying images.

pd-1, alveolar hemorrhage, pembrolizumab, pneumonitis

Computed tomography of the chest before treatment of pembrolizumab. Left pleural effusion, left hilar lymphadenopathy, and left lower tumor were observed (A and B).

PMC6149979_01

Female

A 67-year-old female former smoker was diagnosed with adenocarcinoma on the basis of pathological examination of transbronchial biopsy specimens. Distant metastases were not detected by the whole-body assessment. She underwent a right upper lobectomy with systematic lymph node dissection for lung adenocarcinoma (pT2aN0M0 stage IB: 7th edition of UICC TNM staging). Two years after the surgery, she developed numbness in both feet and was admitted to the emergency room. Spine MRI and chest computed tomography (CT) showed obvious nerve compression due to intradural extramedullary spinal metastasis, suggesting recurrence of her lung cancer. She underwent emergency palliative laminectomy decompression surgery. The pathological features and molecular profiles of the resected intradural extramedullary spinal tumor were reviewed. We diagnosed metastasis from lung adenocarcinoma; neither a mutated EGFR gene nor an ALK fusion gene was detected. Immunohistochemistry revealed high expression of PD-L1 showing a tumor proportion score of 50%-74% on the tumor cell membrane. One month after the palliative surgery, the patient's performance status improved from 3 to 1. However, as left pleural effusion, left hilar lymphadenopathy, and left lower tumor progressed (Figure 1), pembrolizumab treatment (200 mg/day) was initiated. After four cycles of pembrolizumab treatment, she did not have any respiratory symptoms, including coughing, hemoptysis, and dyspnea. However, chest X-ray revealed ground-glass opacities (GGOs) and consolidation in both the lungs. Chest CT showed GGOs and consolidation in both the lungs around the bronchial vascular bundles, along with a crazy-paving pattern (Figure 2A-C). A hematological examination showed increased inflammatory response (white blood cells 8,400/muL and serum C-reactive protein 4.7 mg/dL) and anemia (serum hemoglobin of 9.7 g/dL). Although KL-6 was not high (380 U/mL), SP-D was increased (351 ng/mL). The patient's serum antibody titers against Mycoplasma pneumoniae and Chlamydia pneumoniae were not elevated. The patient's urine was negative for pneumococcal and Legionella pneumophila serotype 1 antigens. Serologic data revealed no abnormal findings suggestive of collagen vascular diseases, including anti-neutrophil cytoplasmic antibody (ANCA), and no microorganisms grew on a sputum culture. Fiberoptic bronchoscopy was performed. Bronchoalveolar lavage (BAL) fluid from the right lower lobe gradually became bloody (Figure 3) with 45% lymphocytes (24.0% CD4, 71.4% CD8), 40% macrophages, 15% neutrophils, and 0% eosinophil. No microorganisms grew on a BAL fluid culture, and no evidence of malignancy was apparent. A transbronchial lung biopsy (TBLB) specimen obtained from the right lower lobe showed thickening of the alveolar walls with myxofibrous and lymphocytic infiltration changes (Figure 4). Although we could not find hemosiderin-laden macrophages in the TBLB specimens, agglutination of red blood cells with focal coagulate change was observed in the air spaces of the alveoli. We diagnosed pembrolizumab-induced ILD with alveolar hemorrhage. After fiberoptic bronchoscopy, oxygen desaturation was found, and oral prednisolone was started at 1.0 mg/kg/day for 2 weeks (initial dose: 40 mg/day) and then the dose was gradually decreased by 5 mg/day every week until reaching a dose of 20 mg/day. The patient's radiographic abnormal findings resolved rapidly (Figure 5), and oral prednisolone was tapered and then discontinued 3 months later without a recurrence of pneumonitis. The patient showed partial responses to pembrolizumab treatment; however, we did not try a challenge readministration of pembrolizumab. Written informed consent was obtained from the patient for publication of this case report and accompanying images.

pd-1, alveolar hemorrhage, pembrolizumab, pneumonitis

High-resolution computed tomography of the chest confirmed the presence of ground-glass opacities with subpleural sparing, interlobular septal thickening, a crazy-paving appearance, and traction bronchiectasis (A-C). Emphysema was also present in both upper lobes.

PMC6149979_01

Female

A 67-year-old female former smoker was diagnosed with adenocarcinoma on the basis of pathological examination of transbronchial biopsy specimens. Distant metastases were not detected by the whole-body assessment. She underwent a right upper lobectomy with systematic lymph node dissection for lung adenocarcinoma (pT2aN0M0 stage IB: 7th edition of UICC TNM staging). Two years after the surgery, she developed numbness in both feet and was admitted to the emergency room. Spine MRI and chest computed tomography (CT) showed obvious nerve compression due to intradural extramedullary spinal metastasis, suggesting recurrence of her lung cancer. She underwent emergency palliative laminectomy decompression surgery. The pathological features and molecular profiles of the resected intradural extramedullary spinal tumor were reviewed. We diagnosed metastasis from lung adenocarcinoma; neither a mutated EGFR gene nor an ALK fusion gene was detected. Immunohistochemistry revealed high expression of PD-L1 showing a tumor proportion score of 50%-74% on the tumor cell membrane. One month after the palliative surgery, the patient's performance status improved from 3 to 1. However, as left pleural effusion, left hilar lymphadenopathy, and left lower tumor progressed (Figure 1), pembrolizumab treatment (200 mg/day) was initiated. After four cycles of pembrolizumab treatment, she did not have any respiratory symptoms, including coughing, hemoptysis, and dyspnea. However, chest X-ray revealed ground-glass opacities (GGOs) and consolidation in both the lungs. Chest CT showed GGOs and consolidation in both the lungs around the bronchial vascular bundles, along with a crazy-paving pattern (Figure 2A-C). A hematological examination showed increased inflammatory response (white blood cells 8,400/muL and serum C-reactive protein 4.7 mg/dL) and anemia (serum hemoglobin of 9.7 g/dL). Although KL-6 was not high (380 U/mL), SP-D was increased (351 ng/mL). The patient's serum antibody titers against Mycoplasma pneumoniae and Chlamydia pneumoniae were not elevated. The patient's urine was negative for pneumococcal and Legionella pneumophila serotype 1 antigens. Serologic data revealed no abnormal findings suggestive of collagen vascular diseases, including anti-neutrophil cytoplasmic antibody (ANCA), and no microorganisms grew on a sputum culture. Fiberoptic bronchoscopy was performed. Bronchoalveolar lavage (BAL) fluid from the right lower lobe gradually became bloody (Figure 3) with 45% lymphocytes (24.0% CD4, 71.4% CD8), 40% macrophages, 15% neutrophils, and 0% eosinophil. No microorganisms grew on a BAL fluid culture, and no evidence of malignancy was apparent. A transbronchial lung biopsy (TBLB) specimen obtained from the right lower lobe showed thickening of the alveolar walls with myxofibrous and lymphocytic infiltration changes (Figure 4). Although we could not find hemosiderin-laden macrophages in the TBLB specimens, agglutination of red blood cells with focal coagulate change was observed in the air spaces of the alveoli. We diagnosed pembrolizumab-induced ILD with alveolar hemorrhage. After fiberoptic bronchoscopy, oxygen desaturation was found, and oral prednisolone was started at 1.0 mg/kg/day for 2 weeks (initial dose: 40 mg/day) and then the dose was gradually decreased by 5 mg/day every week until reaching a dose of 20 mg/day. The patient's radiographic abnormal findings resolved rapidly (Figure 5), and oral prednisolone was tapered and then discontinued 3 months later without a recurrence of pneumonitis. The patient showed partial responses to pembrolizumab treatment; however, we did not try a challenge readministration of pembrolizumab. Written informed consent was obtained from the patient for publication of this case report and accompanying images.

pd-1, alveolar hemorrhage, pembrolizumab, pneumonitis

High-resolution computed tomography of the chest confirmed the presence of ground-glass opacities with subpleural sparing, interlobular septal thickening, a crazy-paving appearance, and traction bronchiectasis (A-C). Emphysema was also present in both upper lobes.

PMC6149979_01

Female

A 67-year-old female former smoker was diagnosed with adenocarcinoma on the basis of pathological examination of transbronchial biopsy specimens. Distant metastases were not detected by the whole-body assessment. She underwent a right upper lobectomy with systematic lymph node dissection for lung adenocarcinoma (pT2aN0M0 stage IB: 7th edition of UICC TNM staging). Two years after the surgery, she developed numbness in both feet and was admitted to the emergency room. Spine MRI and chest computed tomography (CT) showed obvious nerve compression due to intradural extramedullary spinal metastasis, suggesting recurrence of her lung cancer. She underwent emergency palliative laminectomy decompression surgery. The pathological features and molecular profiles of the resected intradural extramedullary spinal tumor were reviewed. We diagnosed metastasis from lung adenocarcinoma; neither a mutated EGFR gene nor an ALK fusion gene was detected. Immunohistochemistry revealed high expression of PD-L1 showing a tumor proportion score of 50%-74% on the tumor cell membrane. One month after the palliative surgery, the patient's performance status improved from 3 to 1. However, as left pleural effusion, left hilar lymphadenopathy, and left lower tumor progressed (Figure 1), pembrolizumab treatment (200 mg/day) was initiated. After four cycles of pembrolizumab treatment, she did not have any respiratory symptoms, including coughing, hemoptysis, and dyspnea. However, chest X-ray revealed ground-glass opacities (GGOs) and consolidation in both the lungs. Chest CT showed GGOs and consolidation in both the lungs around the bronchial vascular bundles, along with a crazy-paving pattern (Figure 2A-C). A hematological examination showed increased inflammatory response (white blood cells 8,400/muL and serum C-reactive protein 4.7 mg/dL) and anemia (serum hemoglobin of 9.7 g/dL). Although KL-6 was not high (380 U/mL), SP-D was increased (351 ng/mL). The patient's serum antibody titers against Mycoplasma pneumoniae and Chlamydia pneumoniae were not elevated. The patient's urine was negative for pneumococcal and Legionella pneumophila serotype 1 antigens. Serologic data revealed no abnormal findings suggestive of collagen vascular diseases, including anti-neutrophil cytoplasmic antibody (ANCA), and no microorganisms grew on a sputum culture. Fiberoptic bronchoscopy was performed. Bronchoalveolar lavage (BAL) fluid from the right lower lobe gradually became bloody (Figure 3) with 45% lymphocytes (24.0% CD4, 71.4% CD8), 40% macrophages, 15% neutrophils, and 0% eosinophil. No microorganisms grew on a BAL fluid culture, and no evidence of malignancy was apparent. A transbronchial lung biopsy (TBLB) specimen obtained from the right lower lobe showed thickening of the alveolar walls with myxofibrous and lymphocytic infiltration changes (Figure 4). Although we could not find hemosiderin-laden macrophages in the TBLB specimens, agglutination of red blood cells with focal coagulate change was observed in the air spaces of the alveoli. We diagnosed pembrolizumab-induced ILD with alveolar hemorrhage. After fiberoptic bronchoscopy, oxygen desaturation was found, and oral prednisolone was started at 1.0 mg/kg/day for 2 weeks (initial dose: 40 mg/day) and then the dose was gradually decreased by 5 mg/day every week until reaching a dose of 20 mg/day. The patient's radiographic abnormal findings resolved rapidly (Figure 5), and oral prednisolone was tapered and then discontinued 3 months later without a recurrence of pneumonitis. The patient showed partial responses to pembrolizumab treatment; however, we did not try a challenge readministration of pembrolizumab. Written informed consent was obtained from the patient for publication of this case report and accompanying images.

pd-1, alveolar hemorrhage, pembrolizumab, pneumonitis

High-resolution computed tomography of the chest confirmed the presence of ground-glass opacities with subpleural sparing, interlobular septal thickening, a crazy-paving appearance, and traction bronchiectasis (A-C). Emphysema was also present in both upper lobes.

PMC7268162_01

Male

Written informed consent was obtained from the patient for their anonymized information to be published in this article. Our institution does not require ethical approval for reporting individual cases. No permission was needed to reproduce any figures in this case report. A 43-year-old male patient presented with a talar AVN associated with progressive pain as a result of a traumatic open ankle dislocation 20 years earlier. The wound was laterally based and moderately contaminated. The patient initially underwent deep debridement and continuous irrigation of the open wound. Finally, he was stabilized with plaster and completed treatment with intravenous antibiotic for 2 weeks. The patient presented an AVN Irwin grade I (Chart 1): segmental articular deficit isolated to either a talar portion; subtype B: AVN deep to the articular segment (Figures 1 and 2). A percutaneous bone biopsy was made in order to confirm the AVN diagnosis (Figure 3). Conservative treatment (12-month period) prior to surgery failed. It consisted of physiokinetic treatment, insoles, and analgesic medication. A diagnostic injection was done in the ankle (Result positive 3/3) and subtalar joint (Result positive 2/3) to recognize origin of pain. The use of patient-specific 3D printed Ti6Al4V ELI PER ASTM F3001 prosthesis with standard screws was deliberated with the patient. A computed tomography (CT) scan slices of 1 mm in all planes of the left ankle were collected and sent to medical application for processing and producing the implant. The manufacturer was Biotrom SA (Argentina); 3D printing vendor: Protolabs (Munich, Germany). The cost of the prosthesis was US$2498. The information was saved into a software (Mimics 11; Materialize , Belgium) that allowed for 3D handling of the bones and articulations (Figure 4). Then, fibular and tibial plafond osteotomy was made to allow correct visualization (not done to correct ankle malalignment) of the lateral region of the talus. When lateral portion of the talus was resected, it showed macroscopic signs of AVN (Figure 5). The Ti6Al4V prosthesis was implanted with a matching less than 1 mm (Figures 6 and 7) and subtalar arthrodesis (evident subtalar chondral lesion was seen under direct vision) was added to correct varus hindfoot. Postoperatively, the patient continued non-weightbearing with a plaster for 8 weeks followed by 2 weeks of controlled weightbearing in a walker boot. He then changed to full weightbearing for 2 weeks. Weightbearing was allowed prior to full CT consolidation. By 4 months, CT showed complete bone integration. X-rays and CT scan showed successful bone integration (Figure 8). At final follow-up (18 months), the patient showed improvement in different scores: foot and ankle ability measure (FAAM) activities of daily living (AVD) improved as 22.62 points (range: 38.09-60.71), FAMM sports enhanced as 35.71 points (range: 28.57-64.28), and the visual analogue scale (VAS) improved 6 points (range: 9-3).

orthopaedics, hemi-prosthesis, occupational therapy, rehabilitation, talus, three-dimensional printing

PMC6475827_01

Male

A 59-year-old male was admitted to our clinic with a 7-month history of unexplained eosinophilia (>1.5 x 109/L) and three-week history of muscle pain in September, 2009. The spleen was palpable 8 cm below the left rib cage. The complete blood count showed hemoglobin levels of 147 g/L, 362 x 109/L platelets, and 22.7 x 109/L leukocytes, with 36.7% eosinophils. A high lactate dehydrogenase was observed (493.5 U/L; normal, <240 U/L). An extensive workup for malignancy, allergies, parasitic, and autoimmune disease were all negative. Bone marrow (BM) specimen showed a hypercellular marrow with hypereosinophilia (26.0%) (Fig. 1A). No increase in blasts was detected. Cytogenetic analysis revealed the karyotype 46, XY in 20/20 of the metaphases examined. Fluorescence in situ hybridization analysis(FISH) showed no signals corresponding to BCR/ABL1gene fusion and myelodysplastic syndromes(MDS) markers [-5/del(5q), -7/del(7q), +8 and del(20q)]. FISH was also negative for rearrangements of PDGFRA, PDGFRB, FGFR1 and CBFB. Because of the lack of genetic mutations, the patient met the clinical criteria for idiopathic hypereosinophilic syndrome (HES) according to established diagnostic guidelines for eosinophilia in 2008 World Health Organization and was treated with predinisone, which led to an improvement in eosinophils, and clinical symptoms. Three years later, the man was examined for abdominal pain and confirmed to have pylethrombosis by computed tomograph. He was treated with thrombolytic therapy successfully. From then on, we managed him with low dose interferon alpha subcutaneously at 3MU per dose TIW (three times a week) and hydroxyurea. The leukocytes and eosinophils were ranged from 5 x 109/L to 10 x 109/L and 0.4 x 109/L to 1.0 x 109/L, respectively, during outpatient following-up. The man was again admitted to our clinic because of fatigue and weight loss in August, 2017. The leukocytes was 5.4 x 109/L (26.5% eosinophils), hemoglobin levels was 72 g/L, and the platelets was 187 x 109/L, BM smear showed slightly hypercellular marrow with eosinophilia(11.0%), multilineage dysplasia, and blasts comprised 7.5% of nucleated cells (Fig. 1B). Cytogenetics were normal, consistent with the findings obtained in September, 2009. MDS-EB-1(intermediate 1 according to the IPSS and intermediate according to the IPSS-R) was diagnosed based on the definition of 2016 World Health Organization (WHO). Therapy was changed to decitabine (20 mg/m2 intravenously on days 1-5). He underwent severe pulmonary infection in the inhibition period of hematopoiesis, and didn't agree to receive cytotoxic chemotherapy any more, except of supportive cares. In February, 2018, the patient complained of weakness and anemia (Hb 61 g/L). The leukocytes and platelets were 55.01 x 109 /L(1% eosinophils) and 10.0 x 109 /L, respectively. BM was hypercellular, with 80.5% blasts, 1% eosinophils (Fig. 1C). There is no new findings in cytogenetics. Flow cytometry analysis demonstrated that the BM blasts were positive for CD13, CD33, and CD117. The patient was diagnosed as acute myeloid leukemia with myelodysplasia related changes (s-AML) and prescribed with reduced intensity IA (idarubicin 6 mg/m2 d1-3, cytarabine 100 mg/m2 d1-7) regimen. Despite two courses of chemotherapy induction, the BM did not exhibit improvement. He expired in May, 2018. Target-NGS of 51 genes, which were known or suspected to have a role in myeloid malignancies, was applied on BM genomic DNA to retrospectivly analyze the molecular evolution from HES to s-AML. We identified three mutations in HES phase, five and seven mutations in MDS and s-AML samples, respectively. The mutated genes included ETNK1, U2AF1, SETBP1, IDH2, and RUNX1. Based on the NGS results, the patient's diagnosis at presentation in 2009 was revised as chronic eosinophilic leukemia not otherwise specified (CEL-NOS), according to the new diagnostic criteria. NGS on saliva DNA confirmed that all these alterations were somatic mutations. Additionally, variant allele fractions (VAFs) provided by NGS can be informative. VAFs represent the fraction of specific mutant sequences (the so-called "reads" provided by NGS) relative to total sequenced reads. Using a simplified model, the original "founding" clones can be identified based on their high VAF whereas clones acquired later in the development of disease would have a distinctly lower VAF. The mutated genes and its VAFs in different disease stages were listed in Table 1.

clonal evolution, hypereosinophilia, next generation sequencing

PMC10311228_01

Female

Case 1: a 38-year-old African female, para 3+0, gave birth to a healthy male newborn weighing 3,010 g through an emergency cesarean section (EMCS) (Table 1). After a period of five days, she developed difficulty in breathing (New York Heart Association (NYHA) class IV) and excessive productive cough with hemoptysis. Past medical history was non-contributory. Upon examination, the patient appeared to be sick looking in severe respiratory distress with a respiratory rate of 30 breaths per minute. Blood pressure was found to be 125/81 mm Hg, however, the patient had tachycardia of 125 beats per minute and oxygen saturation of 79% on room air and 94% on oxygen. Furthermore, the presence of lower limb edema was noted accompanied by jugular venous distention, S3 gallop, and hepatomegaly of 4 cm below the costal margin. Bilateral crepitations were also heard on respiratory examination. The laboratory investigations on admission revealed a normal hematological profile apart from an elevated white blood cell count of 11.84x109/L. COVID-19 and sputum gene X-pert tests for tuberculosis were negative. An elevated D-dimer level was found of 1595 ug/dl. Radiological investigations including a plain chest X-ray, electrocardiograph, echocardiogram (Figure 1), and computed tomography (CT) pulmonary angiogram were performed whose findings have been summarized in Table 2 below. Of note, the patient was found to have bilateral pleural effusion and a left ventricular apical thrombus. After careful interpretation of all the results, the patient was diagnosed with new-onset PPCM in cardiac failure and was immediately admitted to the intensive care unit (ICU). Here, the patient was intubated and started on the medications summarized in Table 3. Nebulization was done every 4 hours and chest physiotherapy was initiated. On day five of admission, the patient s condition improved and was transferred to the acute gynecology ward on oxygen. The patient was discharged on day 20 after admission with the same medications through the cardiac clinic. She remains well to date with no further complications reported.

peripartum cardiomyopathy, heart failure, management, multidisciplinary approach, postpartum cardiomyopathy

PMC10311228_04

Female

Case 4: a 34-year-old African female, para 3+0, who delivered a healthy female newborn weighing 2,790g, presented to the emergency department 15 days post elective Cesarean section with difficulty in breathing (NYHA class IV), excessive productive cough with hemoptysis and bilateral lower limb swelling until the ankles. She reported having orthopnea, paroxysmal nocturnal dyspnea, and palpitations. Her past medical history was unremarkable. Upon presentation, the patient was in severe respiratory distress on 10L/minute of oxygen via a non-rebreather mask. She was afebrile with a blood pressure of 150/99 mm Hg, a pulse rate of 55 beats per minute, a respiratory rate of 21 breaths per minute, and an oxygen saturation of 85% on room air and 98% on oxygen. Physical examination showed bilateral lower limb pitting edema, jugular venous distention, and an S3 gallop. On respiratory exam, crepitations were heard on the right side with reduced air entry on the same side. Laboratory investigations on admission revealed normal hematological levels apart from an elevated white blood cell count of 16.24x109/L and an elevated C-reactive protein of 83. COVID-19 and sputum gene X-pert tests for tuberculosis were negative. A Doppler ultrasound for both limbs was normal. D-dimer levels were within normal. A chest X-ray, an electrocardiograph, an echocardiogram, and a computed tomography pulmonary angiogram were performed (Table 2). Of note, the latter revealed a unilateral pleural effusion on the right side. The patient was admitted to the ward for new-onset PPCM in cardiac failure and was started on the medications summarized in Table 3. On day seven of admission, the patient was doing well and was weaned off oxygen. Her cardiac function improved over a period of one week and her ejection fraction had improved to 58% and was discharged. She remains well to date.

peripartum cardiomyopathy, heart failure, management, multidisciplinary approach, postpartum cardiomyopathy

PMC5646308_01

Unknown

A 51-year-old kidney transplanted patient was admitted to the department of nephrology with abdominal pain and significant weight loss for several weeks. CT scan showed multiple contrast-enhancing peritoneal nodules and large intraperitoneal soft-tissue masses radiologically impressing as severe peritoneal carcinomatosis (Figure 1), a hypodense lesion within the right adrenal gland radiologically appearing as a metastasis as well as enlarged retroperitoneal lymph nodes, while the lung was unremarkable on CT scan. The patient was then referred to our endoscopy unit for tumor screening. Colonoscopy with virtual chromoendoscopy (i-scan) revealed a polypoid lesion at the hepatic flexure with irregular mucosa, hemorrhages, contact bleeding, and a central ulceration (Figure 2). On histopathology, no dysplasia or cancer was found. Importantly, histopathology was also negative for the presence of granulomas. A second colonoscopy for targeted biopsies was initiated and histopathology was again negative for cancer; however, subsequently performed Ziehl-Neelsen stain revealed acid-fast bacteria. In a third colonoscopy, biopsies for microbiological analysis and resistance testing were obtained and DNA of rifampicin-sensitive M. tuberculosis complex was detected using the Xpert MTB/RIF assay on the GeneXpert Dx System (Cepheid, Sunnyvale, CA) on the same day. Immediately thereafter, first-line antituberculostatic treatment was initiated. Liquid culture (BACTEC MGIT , Becton Dickinson, Franklin Lakes, NJ) was positive after 4 days. The strain was identified as M. tuberculosis based on gyrB sequence analysis and phenotypically susceptible to all first-line tuberculostatic drugs. The subsequent course of disease was complicated by episodes of epileptic seizures with aphasia and hemiparesis. Cranial CT and MRI showed bilateral ischemic lesions and contrast-enhancing lesions directly adjacent to the dura, radiologically consistent with multiple septic emboli and tuberculosis manifestation within the CNS (Figure 3). Under tuberculostatic therapy, neurological symptoms slowly ameliorated; however, organic brain syndrome persisted.

PMC9256645_02

Female

A previously healthy 55-year-old female dentist, who had never smoked, was admitted to hospital with transient pneumonia and bilateral consolidation (mainly in the right upper and middle lobes) on the chest X-ray. Pneumonia was resolved with antibiotics treatment. Throughout her professional life, she has been exposed to various types of volatile organic and inorganic compounds. In addition to biological materials, these compounds include silica, heavy metals, and acrylic plastics. She worked with dental prosthesis, various dental operations, and compounds which are used in tooth filling. There was no other specific exposure suspected such as beryllium, aluminum, etc., neither other potential exposures from other jobs or hobbies. Lung function assessments showed a FEV1 of 4.2 L (118% of predicted value), a FVC of 3.3 L (107%), and a FEV1/FVC of 72%. Contrast-enhanced thoracic and abdominal CT revealed an 8 mm nodule in the right upper lobe, growing into the surrounding lung parenchyma and a 7 mm nodule in the interlobular fissure between the right upper lobe and middle lobe. Two pleural nodules with 4 mm in size were seen in the right-side dorsal aspect of the pleura. There was no pleural fluid or pathologically enlarged lymph nodes in the axilla or mediastinum. PET-CT revealed faint metabolic activity in a 9-mm nodule in the right upper lobe, suggesting a Herder model cancer probability of 52%. Therefore, the patient underwent CT-guided biopsy. The first biopsy found suspicious cells, but the second biopsy showed no signs of malignancy. No granulomas were present, and the patient was referred for wedge resection by video-assisted thoracoscopic surgery. Histological examination showed several 3-12 mm necrotizing granulomas; however, no malignancy. Bacterial culture and polymerase chain reaction analysis for Mycobacterium tuberculosis from surgical specimens were negative. Various blood tests and clinical examinations showed no signs of infectious diseases, Wegener's granulomatosis, rheumatoid arthritis, or sarcoidosis. The multidisciplinary team concluded that the patient had pulmonary granulomas secondary to occupational inhalation of silica and other inorganic dust. The patient was referred for control CT scans at 3 and 9 months, and the results were unchanged. The patient was asymptomatic.

PMC9826804_01

Female

A 35 years old female with no comorbidities and an unremarkable medical history came to us complaining of a 3 years old mild progressive mechanical knee pain, it was fairly relieved on analgesics, physical exam revealed mild local tenderness along the distal bony aspect of the distal femur, full range of motion, neurovascular examination was normal, and no other abnormalities in the musculoskeletal system or any signs on knee derangements, x-rays AP and lateral views were obtained showing an ill-defined non-destructive lytic lesion in the distal femur (Fig. 1). Differential diagnosis was simple cyst, aneurismal bone cyst or chondromyxoid fibroma so MRI was ordered and it showed a well-defined heterogenies non-aggressive lesion in the distal femur with low signal on t1 weighted images and mixed signal on t2 and PD images measuring 7 x 4 x 3 cm (Fig. 2). while a simple bone cyst doesn't correlate with the age of the patient and ABCs usually have a characteristic MRI appearance -multiple fluid lines- and tend to be more expansile and aggressive, chondromyxoid fibroma might be the most probable diagnosis but it is usually more demarcated from the adjacent bone with a scalloped and a sclerotic rim. Malignant bone lesions don't have that subtle hideous presentation, and of course infection the great mimicker of lesions is a possibility, however there is no local nor systemic symptoms of infection and the labs were within normal limits. Due to the untypical radiological and clinical appearance the decision of biopsy was made to optimize the planning of management which came in as benign bone tissue with intervening fibrous tissue and addition four giant cells suggesting aneurismal bone cyst after correlation with the radiological examination (Fig. 3). So we went for surgery with extensive curettage and reconstruction of the gap left behind, however the visual look of the lesion intra-operatively was not correlating with ABC so the decision of marginal resection was made and the gap was filled with bone cement and the bone was prophylactically fixed with an anatomical distal femur plate (Fig. 4). The resected tissue was send again for histological study and came in as fragments of bony and inflamed fibrotic tissue showing granulation tissue formation and fragments of pink acellular laminated material suggestive of germinal layer of the hydatid cyst (Fig. 5). The drain was withdrawn the next day of surgery and the patient was discharged into physiotherapy program with partial weightbearing and prophylactic anticoagulant medicine based on her weight and it was referred to a general surgeon consultant where full body CT scan was made and it came negative with no other lesions identified. Infections control consultant was made and the patient was given a course of Albendazole for 3 months.

bone, case report, hydatid cyst, infection

PMC7113432_01

Female

A 52-year-old smoker woman presented to our hospital with a 6-week history of anorexia, weight loss, fatigue, productive cough, exertional dyspnea, and hoarseness. She was diagnosed with pulmonary and probable laryngeal tuberculosis and was commenced on a 6-month, antituberculous drug regimen. Clinical course was uneventful and she was discharged 7 days after admission without breathlessness and with minimal dysphonia. At a 3 month follow-up visit, the patient complained of worsening exertional dyspnea for the previous month, without other associated symptoms. Chest x-ray displayed no signs suggestive of active pulmonary tuberculosis. Dual bronchodilator therapy was prescribed but, as dyspnea turned out to be refractory, spirometry was done. The flow-volume loop was diagnostic of fixed upper airway obstruction (Fig. 1). Bronchoscopy revealed an approximate 90% tracheal stenosis about 3.5 cm below the glottis (Fig. 2, A) which prevented bronchoscope from passing through the stenosis. A subsequent chest CT scan showed severe proximal tracheal narrowing (Fig. 2, B-D). Tracheal aspirate samples were negative for acid-fast bacilli and their culture did not yield Mycobacterium tuberculosis. Rigid bronchoscopy with balloon dilatation (Storz, California, US) under general anesthesia was scheduled. The first session was initially performed with a bronchoscope of 7.5 mm outer diameter, then substituted for another of 8.5 mm. Following this session, residual stenosis was almost 30% of the normal tracheal lumen and patient's dyspnea alleviated considerably. One year after the first session, however, a second bronchoscopic dilatation was undertaken because her usual exertional dyspnea had recently worsened. This second intervention was done using a bronchoscope of 12 mm external diameter, residual stenosis being around 20% of the normal tracheal lumen. Eventually, she became symptomless. There were no adjunctive treatments given. When last seen, 1 year after the second bronchoscopic session, she remained asymptomatic.

bronchoscopy, tracheal stenosis, tuberculosis

PMC9122666_01

Male

A 38-year-old man, who had no history of the disease, was admitted to the Department of Infectious Diseases due to repeated fever, headache, and scattered rashes on his limbs. The fever persisted 13 days before the hospital visit, his highest axillary temperature was 38.5C, and this was accompanied by fatigue and headache. Routine blood examination at our hospital suggested the fever was due to infection, and he was put on ceftriaxone treatment for 1 week. However, the fever did not resolve, and scattered red rashes were seen on his limbs 7 days ago. The rashes subsided after self-administration of anti-allergic drugs. The headache worsened 1 day after the treatment, and this was accompanied by a slow response, thus he was admitted. He was healthy and had no history of bad habits such as drug abuse, having multiple sexual partners, and homosexual practice. The patient's vital signs were as follows: 125/78 mmHg brachial artery blood pressure, 38 C axillary temperature, 84 bpm heart rate, and 22 bpm respiration rate. Additionally, the patient exhibited consciousness, slow reaction, negative neck resistance, pharyngeal hyperemia, no swelling of the tonsils, and no cardiac, pulmonary, or abdominal abnormalities. He did, however, have a few scattered rashes on his extremities, with no evidence of superficial lymph node swelling, normal muscle strength in his extremities, and negative nerve localization signs. A routine blood examination performed one day before admission, revealed a total white blood cell count of 10.89x10^9/L, a neutrophil percentage of 37.6%, a lymphocyte count of 6.22x10^9/L, as well as C-reactive protein (CRP) and Procalcitonin (PCT) levels of 0.93 mg/l and 0.13 ng/mL, respectively. Results from liver function analysis revealed an alanine aminotransferase (ALT) of 148 U/L and aspartate aminotransferase (AST) of 106 U/L. The antigen/antibody test for the human immunodeficiency virus was negative, while Chest CT showed no abnormalities. Following hospitalization, routine blood tests revealed a total white blood cell count of 10.84x10^9/L, reduced neutrophil percentage (35.4%), an increased lymphocyte percentage (57.2%), a lymphocyte count of 6.20x10^9/L, a monocyte count of 0.69x10^9/L, a CRP of 1.54 mg/ L and PCT: 0.1 ng/ mL (Figure 1). The blood gas analysis indicated normal results, but the liver function test revealed ALT and AST levels of 92.4 and 50.3 U/L, respectively. HCMV and EBV antibody assays revealed positive and negative IgG and IgM respectively, but no HCMV or EBV DNA. A lumbar puncture revealed a cerebrospinal fluid pressure of 110 mmH2O, while results from CSF routine tests revealed negative occult-blood test, light yellow, transparent, Pan's test 4+, nucleated cell counts of 380 /ul, neutral 1%, lymphoid 99%. Additionally, his lactate dehydrogenase increased (161 U/L), glucose levels decreased (2.0 mmol/ L), chloride level decreased (117.8 mmol/L), and his protein levels were >6000 mg/ L. Simultaneously, he had normal electrolyte and blood glucose levels, and the CSF smear test for Cryptococcus was negative. Adenosine deaminase activity in the CSF was 6.1 U/L and the electroencephalogram (EEG) was normal. Brain enhanced MRI+DWI scan showed no obvious abnormalities. Similarly, a Color Doppler ultrasound revealed no abnormalities in the lymph nodes in his neck, underarms, or both sides of the groin. Color Doppler ultrasound of the hepatobiliary, pancreas, and spleen revealed no obvious abnormalities. On the second day of hospitalization, we collected 3 mL of his CSF and sent it to Hangzhou Jieyi Medical Laboratory (Hangzhou, China) for metagenomic next-generation sequencing. On the 4th day, the mNGS report confirmed the presence of 12 human immunodeficiency virus type 1 (HIV-1) sequences (Figure 2), but no other pathogenic microorganisms (including bacteria, viruses, mycobacteria, fungi, and parasites, among others) were detected. On the third day, both the blood tuberculosis T cell spot test (T-SPOT. TB) and the CSF cryptococcal capsule antigen assays were negative. On the fifth day, mycobacterium tuberculosis DNA analysis from CSF revealed negative results, with no evidence of bacterial growth in either the cerebrospinal fluid or blood cultures. Lumbar puncture and cerebrospinal fluid examination were performed on the 6th, 9th, and 18th day respectively. The results indicated a progressive decrease in nucleated cell count, while sugar, chloride, and protein levels gradually returned to normal (Table 1). Additionally, CSF smears were negative for Cryptococcus. On the 6th day, 2 mL of CSF was collected and analyzed for the presence of HIV RNA qPCR 910 copies/mL, and blood HIV RNA qPCR 1.37x10^5 copies/mL (Figure 3). HIV antigen/antibody tests, performed between the 5th and 10th days, again showed negative results (the fourth generation), whereas a positive result was obtained on the 17th day. On the 18th day, a Western blot (gp120, gp160, gp41, P24) assay confirmed the presence of HIV in the blood (Table 2). On the 6th day, cell counts revealed CD4+ and CD8+ counts of 447 and 600/ul, respectively. On the 10th day, these counts had decreased, as shown by a CD4+ cell count of 293/ul, and a CD8+ cell count of 517/ul. On the second day of hospitalization, tuberculous meningitis was considered based on relevant blood and CSF examination results. Consequently, the patient was administered four diagnostic anti-tuberculosis treatments: isoniazid, rifampicin, moxifloxacin, and linezolid. Additionally, he was administered an intravenous injection with an anti-inflammation dexamethasone needle and symptomatic treatment, which included compound glycyrrhizin for liver protection. On the 6th day, all anti-tuberculosis drugs and dexamethasone needles were discontinued, except for glycyrrhizin (for liver protection) and adequate fluid rehydration. On the second day of hospitalization, the patient's body temperature gradually decreased, before returning to normal. His headache and condition improved, and he was transferred to an outpatient clinic on the 18th day for antiretroviral therapy (ART). His medical history was obtained regarding past protected same-and anal sex activities, 8 days before the onset of symptoms.

fiebig stage i, acute hiv infection, aseptic meningitis, mngs

PMC4784188_01

Male

A 70-year-old man was scheduled for a left video-assisted thoracoscopic surgery. No large airway anomaly was reported on the preoperative computed tomography (CT) scan. After standard uneventful induction, the patient was intubated with a single lumen endotracheal tube (SLT). Fiberoptic bronchoscopy (FOB; Olympus America Inc., Center Valley, PA, USA) was used to aid placement of a 7F Uniblocker (Fuji Systems Corp., Fukushima, Japan) inside the left mainstem bronchus (LMB) and revealed an odd configuration of central airways [Figure 1A]. The initial diagnosis was the inadvertent placement of the SLT in the right mainstem bronchus (RMB). However, after confirming the depth of the tube to be 21 cm and no change in the appearance of the tracheal anatomy on withdrawing the SLT several centimeters, it was realized that the SLT was indeed in the trachea. The FOB was advanced into the rightmost bronchus, which showed two segmental bronchi. FOB of the middle lumen showed an absence of the RUL bronchus, instead appearing to bifurcate into the right lower and middle lobes similar to the bronchus intermedius in normal patients. The leftmost lumen had the same anatomy as a normal left bronchus. After a thorough assessment of the airway anatomy, diagnosis of a low-riding tracheal bronchus (TB) versus tracheal trifurcation was made. To isolate the left lung, the bronchial blocker (BB) was placed in the leftmost lumen, and the surgery was accomplished uneventfully. After the surgery, our attempts to look for the elusive TB in the preoperative axial CT scan images and chest radiograph were not successful. Only after a radiologist performed a minimum intensity projection of coronal reconstruction, were we able to identify the TB that was missed in the preoperative reporting [Figure 1B].

aberrant tracheal anatomy, lung isolation, one lung ventilation tracheal bronchus

PMC6675970_01

Female

In 2005, a 30-year-old, never-smoker, Caucasian woman with normal body mass index (BMI: 20 kg m-2) was diagnosed with Hodgkin's lymphoma. She received chemotherapy and autologous HSCT and, one year later, allogeneic HSCT preceded by a myeloablative treatment including cyclophosphamide, cyclosporine A, methotrexate and 12 Gy total body irradiation (TBI). PFTs were all within their respective normality range before allogenic HSCT (Fig. 1), but at 3-month follow-up they revealed a moderate decrement of TLC (3.70 L; 72% of predicted; z-score: -2.47), forced vital capacity (FVC) (2.63 L; 66% of predicted; z-score: -2.80), forced expiratory volume in 1 s (FEV1) (2.21 L; 67% of predicted; z-score: -2.72) and DLCO (15.6 mL min-1 mmHg-1; 67% of predicted; z-score: -2.70) whereas residual volume (RV) was within the normal range but increased from pre-HSCT value, thus resulting in an RV % of predicted to TLC % of predicted ratio (RV/TLC) of 140%. This pattern and computed tomography (CT) scan findings were considered consistent with IPS and eventually treated with oral corticosteroids in addition to maintenance cyclosporine A. Over the following months, the patient experienced progressive exertional dyspnea with dry cough. At 18-months follow-up, PFTs showed the new onset of a severe (FEV1: 1.80 L; 48% of predicted; z-score: -4.01) obstructive abnormality with borderline decrement of FEV1/FVC ratio (0.72; z-score: -1.73) and TLC (4.03 L; 78% of predicted; z-score: -1.91) but RV still within the normal range. Thereafter, TLC returned above the lower limit of normal but FEV1/FVC further decreased, without significant bronchodilator response to 400 mug inhaled salbutamol, while RV/TLC remained >120%. These findings, in the absence of respiratory infections, supported a diagnosis of BOS. A course of inhaled fluticasone/formoterol, oral azithromycin, montelukast, and corticosteroids led to symptom relief. At 7-year follow-up, chest auscultation revealed short wheezes preceded by crackles from mid-to-end inspiration over the lower lung zones bilaterally and full-expiration CT showed bilateral mosaic hypo-attenuation areas suggestive of air trapping. Subsequently, over the next five years TLC and DLCO decreased progressively, while severe obstruction persisted and RV tended to decrease. At 12-year follow-up, TLC and DLCO were severely decreased while RV/TLC was 149% and FEV1/FVC marginally reduced. CT scans showed "wedge-shaped" pleural thickening of upper and middle lung zones bilaterally, with reticular fibrotic pattern involving 16% of lung volume, without inspiratory low-attenuation areas suggestive of emphysema (Fig. 2A and B). Three months later, the patient had a right pneumothorax requiring apical resection by video-assisted thoracoscopy. Histology showed fibro-elastosis of sub-pleural lung parenchyma and visceral pleura, with no inflammation, or granulomas, or emphysematous areas (Fig. 2C and D). Eventually, her condition improved and she was discharged from the hospital.

air trapping, bronchiolitis obliterans syndrome, haematopoietic stem-cell transplantation, idiopathic pneumonia syndrome, lung restriction, pleuroparenchymal fibroelastosis

B) Automatic quantitative 3D analysis of the entire lungs. It is noteworthy, the significant extent of high attenuation areas (HAA-200 to -700 HU) consistent with fibrosis (16% of CT volume) and the lack of low attenuation areas (LAA<-950 HU) consistent with emphysema.

PMC4515255_01

Male

An 81-year-old Caucasian male presented to the emergency department with shortness of breath and hemoptysis. Over the previous one to two months, the patient experienced fatigue and increasing shortness of breath. Episodes of hemoptysis were two to four times per day. His past medical history included ureteral and bladder cancer, recurrence of papillary tumor and prostatic urethra status after right nephroureterectomy and chemotherapy, deep vein thrombosis, hypertension, type 2 diabetes mellitus, and hypothyroidism. Regarding social history, the patient farmed full-time in his retirement, and he had recently cleaned out his chicken coop, which contained several months of built-up feces and straw bedding. Upon admission, initial laboratory values included sodium 143 mEq/L, potassium 4.2 mEq/L, chloride 106 mEq/L, blood urea nitrogen 58 mg/L, creatinine 4.29 mg/dL, glucose 118 mg/dL, white blood cell count 9.7 x 103/mm3, hemoglobin 6.4 g/dL, and platelet count 169 x 103/mm3. Liver function test values were alanine aminotransferase 6 U/L, aspartate aminotransferase 13 U/L, and alkaline phosphatase 55 U/L. The patient was on warfarin for deep vein thrombosis, and anticoagulation results indicated prothrombin time (PT) 108.2 seconds, international normalized ratio (INR) 9.6, and activated partial thromboplastin time (aPTT) 49 seconds. Numerous other laboratory tests were completed, including cytoplasmic anti-neutrophil cytoplasmic antibodies (c-ANCA), perinuclear anti-neutrophil cytoplasmic antibodies (p-ANCA), glomerular basement membrane antibody IgG, urine Histoplasma/Legionella/Streptococcus pneumoniae antigens, QuantiFERON tuberculosis gold, and beta-glucan. All of these tests were negative. Of note, beta-glucan test does not reliably detect Cryptococcus, Zygomycetes, or Blastomyces dermatitidis. Abnormal laboratory values included c-reactive protein 8.9 mg/dL, automated sedimentation rate >120 mm/hr, N-terminal pro-brain natriuretic peptide (NT-proBNP) 9,789 pg/mL, and troponin T 0.106 ng/mL. The initial differential diagnosis and assessment included inflammatory pneumonitis, infection, and immunologic pathology. The patient was initiated on ceftriaxone and azithromycin, and a respiratory culture was obtained. Throughout the initial hospital course, his oxygen saturation dropped on a nonrebreather mask, and the patient was agreeable to elective intubation with bronchoscopy. Antibiotics were broadened to levofloxacin, piperacillin/tazobactam, and vancomycin, and corticosteroids were added. Cystogram was completed per urology which showed reflux with nonobstructive hydronephrosis, and nephrology was consulted to rule out other causes of the patient's acute kidney injury, none of which were definitive diagnoses. On hospital day 19, the patient's blood cultures were positive for yeast, which was presumed to be Cryptococcus neoformans, and liposomal amphotericin B 300 mg (3.1 mg/kg actual body weight) daily was initiated. On hospital day 23, Cryptococcus neoformans was identified in the blood via matrix assisted laser desorption/ionization-time-of-flight (MALDI-TOF) mass spectrometry and confirmed via a biochemical method (API 20C strip). A lumbar puncture was completed which also grew Cryptococcus neoformans. Flucytosine was initiated on day five of liposomal amphotericin B treatment (hospital day 23). As the patient was receiving intermittent hemodialysis at the time of flucytosine initiation, a dose of 2,500 mg (25.8 mg/kg actual body weight) every Tuesday, Thursday, and Saturday after dialysis sessions was chosen. See Table 2 for a schedule of the hemodialysis sessions the patient received. On hospital day 27, the patient was initiated on continuous renal replacement therapy due to hemodynamic instability with the addition of multiple vasopressors (norepinephrine, phenylephrine, and vasopressin). The patient remained intubated, sedated, and paralyzed for facilitation of mechanical ventilation. Continuous venovenous hemofiltration (CVVH) was initiated (with citrate for anticoagulation) as the primary mode of dialysis and was maintained on the following settings: total replacement fluid rate, 2,500 mL/hr; blood flow rate, 300 mL/min; preblood pump rate (PBP) (citrate flow rate), 450 mL/hr; and ultrafiltration rate, 100-400 mL/hr. Our institution utilizes the Gambro PrismaSATE system with the PrismaSATE HF 1400 polyarylethersulfone filter. Due to inability to ultrafiltrate with CRRT at all times, the average fluid removal rate was 265 mL/day (11 mL/hr) over 3 days (hospital days 27-29). As a result of the dialysis change to CVVH, the flucytosine dose was increased to 2,500 mg (25.8 mg/kg actual body weight) by mouth every 12 hours. Of note, this flucytosine dose was significantly conservative, as it utilized a total daily dose of 50 mg/kg/day, as compared to some literature that recommends up to 150 mg/kg/day divided. The choice for conservative flucytosine dosing was made based on the patient's baseline thrombocytopenia; the patient's platelet count was 39 x 103/mm3 the day CVVH was initiated. Over the 3 days of CVVH, the patient had a mean urine output of approximately 0.21 mL/kg/day, classified as nonoliguric renal failure. Flucytosine was discontinued on hospital day 29 due to thrombocytopenia, and high dose fluconazole was added. Liposomal amphotericin was replaced with conventional amphotericin on hospital day 37. The patient had negative blood cultures on hospital days 32 and 34. The patient passed away on hospital day 47 from refractory hypoxemic respiratory failure, as life prolonging efforts were withdrawn per family request.

PMC6394363_01

Male

A 43-year-old man presented to the emergency room complaining of tongue paresthesia, slurred speech, and weakness. These symptoms had developed insidiously and progressively over the past 4 weeks. The patient described muscular weakness initially involving the left side of the body, which soon included the right side. He also referred a decrease in sensitivity in the left half of the body. He denied fever, headache, weight loss, dyspnea, convulsions, visual symptoms, incontinence, and vertigo. His past medical history was unremarkable, except for smoking (15 pack-years) and recreational alcohol consumption. The neurological examination revealed a hyposensitivity in the right hemiface, as in the right half of the body, and grade 4 of muscle strength of the left upper limb. The remaining physical examination was normal as were his vital signs. The initial laboratory work-up was normal; however, further investigation revealed a positive serology for HIV infection by the enzyme-linked immunosorbent assay and Western blotting. The TCD4+ peripheral count was 75 cells/microL, and the HIV-1 RNA viral load in the blood was 97,911 copies/mL (branched DNA) or Log 4991. The brain computed tomography (CT) revealed two hypodense foci in the right cerebral hemisphere's white matter, in the right frontal lobe, and in the high parietal region, without contrast enhancement or midline shift. Due to the imaging findings in a patient with HIV, neurotoxoplasmosis was the initial working diagnosis. Therefore, pyrimethamine and sulfadiazine were promptly prescribed. Two weeks later, this antibiotic regimen was withdrawn since (i) the patient's clinical features did not improve; (ii) the serology for toxoplasmosis tested negative for immunoglobulin IgG and IgM; and (iii) the lesions increased in size and became more evident in controlled CT. The brain magnetic resonance imaging (MRI) showed extensive discontinuous hyper signal areas on T2- and FLAIR-weighted images in the hemispheric white matter, with predominance in the right frontotemporal subcortical region, as well as in the splenium of the corpus callosum and the brainstem (Figure 1). These findings raised the diagnosis of PML. At this time, the cerebrospinal fluid (CSF) examination showed leukocytes of 2 cells, erythrocytes of 14 cells, protein of 25 mg/dL, and glucose of 58 mg/dL. CSF culture was negative for bacteria, mycobacteria, and fungus. The polymerase chain reactions (PCR) for Mycobacterium tuberculosis, Cryptococcus spp, Toxoplasma gondii, and JCV were negative, which permitted the initiation of highly active antiretroviral therapy (HAART). The patient's outcome was troublesome with progressive worsening of his neurological status, and slow progression to spastic paraparesis. At the end of the fourth week of hospitalization the patient maintained only the distal movement of the right upper limb, hyperreflexia, tetraplegia in a pyramidal pattern, generalized spasticity and hypertonia, ophthalmoplegia, facial amimia, gaze fixation inability, anarthria, and the inability to swallow. According to this outcome, the diagnosis of PML was highly considered, and because of the deterioration of the neurological status concomitantly after HAART, the hypothesis of immune reconstitution inflammatory syndrome-PML (IRIS-PML) was considered. Thus, prednisone 1 mg/kg was started. However, no improvement was observed. Meanwhile, the patient presented an episode of bronchoaspiration and septic shock, and died after 7 weeks of hospitalization. An autopsy was performed after the informed consent signed by his wife.

acquired immunodeficiency syndrome, autopsy, diagnosis, jc virus, leukoencephalopathy, progressive multifocal

PMC6197753_01

Female

A 57-year-old Caucasian woman was admitted to our surgical department. She complained of persistent nagging epigastric pain and pain behind the sternum, in the left hypochondrium, constant heartburn, belching, daily vomiting of eaten food and liquid, impaired swallowing, fever up to 39 C. The woman had no previous medical or surgical history. The preoperative study included esophagogastroduodenoscopy (EGD), barium swallow esophagoscopy and chest spiral computed tomography (CT) scan. EGD revealed large pouch of the right esophageal wall in middle and lower third of the esophagus with signs of inflammation, ulceration and necrosis and retained food in the pouch. Barium esophagogram demonstrated 50 x 100 mm epiphrenic diverticulum on the right side and in the lower third of the esophagus which contained food (Fig. 1). CT scan confirmed the diagnosis, showing 77 x 53 mm diverticulum in the lower third of the esophagus. Complete blood count (CBC) revealed leukocytosis along with "left upper shift" and increased erythrocyte sedimentation rate (ESR). Considering esophageal wall necrosis extended more than 70 mm, the setting of the esophageal stent was inappropriate. Thereby, it was decided to perform laparoscopic-thoracoscopic esophageal resection (Ivor Lewis operation). The time from the moment of admission to the hospital until the operative treatment was 2 days.

case report, epiphrenic diverticulum, esophageal diverticulum, laparoscopic esophageal surgery, laparoscopic-thoracoscopic esophageal surgery, necrotic diverticulitis

PMC4235491_01

Female

The patient was a 57-year-old, right-handed woman with a 4-year history of rapid progressive dementia of Alzheimer type, which was previously diagnosed outwards by neuropsychological examination. The diagnosis was confirmed by magnetic resonance imaging, fluorodeoxyglucose positron emission tomography, and examination of cerebrospinal liquid with measurement of dementia parameters. Her psychiatric history included two depressive episodes 26 and 18 years previous, following critical life events, which remitted in the course of months without specific therapy. She was admitted to our clinic for evaluation and treatment of severe behavior disturbances, including severe restlessness, yelling, crying, refusal to eat and drink, physical aggression, and resisting care, which made further caretaking of the patient at home by family members impossible. On hospital admission, she exhibited highly agitated behavior with anxiety, near-continuous pacing, crying, and repetitive local outbursts, and could not be redirected. She attempted hitting unit staff during washing and feeding. Whether psychotic symptoms were partly responsible for the observed behavioral disturbances remained unclear. On the Pittsburgh Agitation Scale (PAS), which rates the severity of four behavior groups (aberrant vocalizations, motor agitation, aggressiveness, and resisting care) on a scale of 0-4 with higher scores indicating more severe agitation, she scored 11 (out of 16) points. Verbal communication with the patient and neurocognitive evaluation was substantially hindered by impairment of language comprehension. The patient was not able to perform specific neuropsychometrics, like the Mini-Mental State examination. She had difficulties falling and staying asleep and failed to assist in performing activities of daily living. Her medication on admission included the acetylcholinesterase inhibitor rivastigmine patch (9.5 mg/d) and antipsychotic agent quetiapine (50 mg/d). Complete blood count, electrolytes, thyroid, liver, and kidney function tests, urinalysis, electrocardiogram, and physical exam were all normal. Her agitation symptoms proved unresponsive to combined behavioral therapy. Multiple trials of various psychopharmacologic agents were also ineffective: no improvement could be observed with quetiapine at increased doses (up to 175 mg/d), risperidone (up to 2.5 mg/d), melperone (up to 100 mg/d), and pipamperone (up to 80 mg/d). In due consideration of depressive episodes in her medical history, we started an antidepressive combination therapy with sertraline (200 mg/d) and mirtazapine (30 mg/d), which induced an improvement of sleep but no decrease in agitated behavior. Treatment with lorazepam (up to 4 mg/d) brought about a temporary affective loosening, which lasted only 4 days. After 9 weeks in our hospital, ECT was initiated. At this time, the patient was receiving rivastigmine (9.5 mg/d), sertraline (200 mg/d), and mirtazapine (30 mg/d). Due to her inability to give informed consent, her daughters - who were also her legal guardians - agreed to the treatment, after detailed information and discussion. To potentially minimize reversible cognitive adverse effects of ECT we decided to use right unilateral electrode placement, dose titration (ie, evaluation of the patient's individual seizure threshold), a treatment frequency of two sessions per week, a pulse width of 0.25 ms, and S-ketamine for anesthesia. ECT was administered with a Thymatron IV device (Somatics, LLC, Lake Bluff, IL, USA). Weight-adjusted S-ketamine (~1.2 mg/kg) was used for anesthesia induction, followed by succinylcholine for muscle relaxation. The seizure threshold was determined at the first treatment (<50 mC). Following sessions were conducted at 150 mC (second - fifth session) and 200 mC (sixth - eighth session). Sufficient seizures, with respect to quantified ictal parameters, were achieved. PAS scores were determined weekly to assess the clinical severity of agitation symptoms. A marked difference in the clinical presentation of the patient was noted after just two ECT treatments: the patient was noticeably less agitated, and crying occurred only for short episodes. Her improvement continued throughout the entire course of eight treatments given over 26 days. She stopped yelling and crying, showed no aggression, smiled spontaneously, and was more redirectable. The patient continued to pace, but she was able to sit and lay down for longer periods. She showed significant reduction in her total PAS score from baseline (11 points) during and after ECT (2 points) (Figure 1). A worsening of cognitive functions under ECT was not observed. On the contrary, the patient started to eat and drink by herself and was more cooperative in other daily care activities, like washing and dressing. Family members claimed to be able to verbally and nonverbally communicate better with the patient (eg, she followed lowest level instructions). The ECT treatment was tolerated well, with signs of headache after the first three sessions. In the third week of treatment, a single self-limiting, spontaneous generalized seizure was observed. The patient was discharged 5 days after the last ECT treatment. The improvement in agitation symptoms was present on hospital discharge. The guardians refused maintenance ECT since the patient moved away from our clinic to be taken care of by other family members. Katamnestic data on clinical presentation and behavioral symptoms of the patient were collected, by caregiver interviews, every 2 weeks over a period of 4 months after hospital discharge. Based on this information, PAS scores were determined. The improvement of agitation symptoms initiated by ECT lasted for approximately 12 weeks without any additional therapy other than rivastigmine, sertraline, and mirtazapine (Figure 1). In the follow-up period, two further self-limiting, spontaneous generalized seizures were reported.

cognition, dementia, disinhibition, electroconvulsive therapy, emotional distress

PMC3350001_01

Female

A 45-year-old woman, normotensive, nondiabetic, presented at the outpatient clinic of our institute. Her chief complaints were progressive pain, numbness, and tingling along the inner surface of her left forearm and lateral aspect of the fifth finger for one month. She had a history of fall (on her left shoulder) from about three meters two months back. At that time she was admitted on short stay basis and after certain investigations she was discharged home. She had no other complaints and no history suggestive of tuberculosis. General physical examination was normal in all aspects. There was tenderness in the left supraclavicular region. Left upper limb was warm, nontender, and distal pulses were present. Reflexes were intact. Her motor functions were normal. However, sensations were relatively diminished along medial aspect of left forearm and hand. A plain X-ray of cervical spine showed a left cervical rib which was fractured (Figure 1). Electrophysiologic study suggested the presence of left lower brachial plexus neuropathy. It was decided to remove fractured cervical rib. The patient was admitted, and cervical rib was excised along with first rib through supraclavicular approach. The patient made an uneventful recovery and was discharged on the 5th postoperative day. Her symptoms resolved completely in the postoperative period.

PMC7757277_01

Male

We report the case of a fifty years old patient with past medical history of cerebral palsy referred from ophthalmology department for right supra orbital swelling involving the eyelid. The beginning of signs is about four months by the onset of a sub cutaneous mass at the eyelid; he consulted at the ophthalmology department where after clinical examination a brain computed tomography (CT) scan was performed before his reference to the Neurosurgery Department. At the admission in our department the physical examination found a cachectic patient, complaining with fever in the evening and presenting a right supra orbital mass (Figure 1); the mass is non inflammatory, soft and painless. The brain CT scan objectified an osteolytic lesion of the orbital roof extended to frontal bone associated to an epidural lesion (Figure 2). We operated the patient under general anesthesia, we performed a skin incision through the right eyebrow; after the dissection of the subcutaneous tissues, we discovered and evacuated thick pus under the eyelid. We also discover an osteolytic lesion at the orbital roof extended to the frontal bone (Figure 3). We performed a biopsy of the bone lesion and the histological examination objectified a caseo follicular tuberculosis. The immediate post operative outcome was favorable with the disappearance of the collection. The patient was exited from the hospital 2 weeks after with a reference letter to infectious diseases department for anti tuberculosis treatment. The patient received the anti tuberculosis treatment for twelve months according to the national program. The control brain CT scan was performed after the completion of the treatment and there was no recurrence of the collection (Figure 4).

orbital, osteolytic, tuberculosis

PMC4154277_01

Female

A 25 year old woman was referred with a history of chronic headache for a period of three months. The headache was severe and refractory to NSAIDs or other pain relievers. There was no history of chills and fever, gait disturbance, hearing loss and memory problems. No history of using illicit drugs such as cocaine, alcohol, cannabis was also found. Drug history was negative for oral contraceptive pills, nalidoxic acid, tetracycline, corticosteroids, vitamin A and other drugs. She was student, lived in an urban area with history of travels to rural areas. No history of using unpasteurized milk and contact with animals were found. In physical examination, vital signs were normal. Generally, she was cooperative with intact orientation. Cranial nerve examinations were normal and meningeal signs were not detected. There was a significant papilledema in ophthalmologic examination. Deep tendon reflexes (DTRs) in upper and lower limbs were normal. Muscle forces in proximal and distal regions of lower and upper limbs were also normal. No impairment in the sensation of extremities was detected. Gait was intact with no ataxia and tremor. Psychological examination was also done. There was not any abnormality in mood and affect evaluation and no cognitive impairment was also observed. Laboratory studies including complete blood count with differentiation (CBC/ diff), prothrombin time (PT), partial thromboplastin time (PTT), international normalized ratio (INR), blood urea nitrogen, creatinine (BUN,Cr) and liver function tests (LFT) were normal. An elevated ESR was detected (68mm/hour). HBS Ag, HCV Ab, VDRL and HIV Ab were also negative. Anti-nuclear antibody (ANA), Anti-neutrophil cytoplasmic antibodies (ANCA), C3 and C4 were in normal range. Brain CT scan in addition to T1 and T2 weighted brain MRI plains after gadolinium injections were also performed that revealed no pathologic findings. The patient underwent lumbar puncture. Cerebrospinal fluid appeared xanthochromic and presented with a high opening pressure (280 mmH2O), low glucose (43mg/dl) and elevated protein levels (338mg/dl). Spinal fluid analysis showed leukocytes. Brucella (capt test) tube agglutinin was positive at 1/2560 titers in blood and positive at spot and 1/2560 titers in CSF. Tuberculosis PCR test was negative for the CSF sample. In summary, we had a case with a history of chronic headache characterized by increased intra-cranial pressure (ICP). Papilledema was the only positive finding in the initial physical examination. SAT (serum antibody test) was the only positive finding for brucella within the laboratory test. Other investigations including imaging studies were normal. The patient received intravenous cefteriaxone 1gr BID and oral doxycycline 100mg BID and rifampin 600 mg once daily for 1 month; and then rifampin continued for 14 months. Headache began to improve during treatment and disappeared after 3 months.

brucellosis, headache, papilledema

PMC9610685_01

Female

A 37-year-old female patient who received epidural anesthesia during childbirth presented to the neurosurgical service eleven months postpartum for worsening headaches with nausea, vomiting, vision changes, and weight loss. Here, a medical history was significant for peripheral neuropathies, unspecified mood disorder, herpes labialis, hepatitis C (HCV), intravenous substance abuse (including heroin and cocaine, now on buprenorphine), and noncompliance. Her medications before admission included gabapentin 300 mg daily, buprenorphine 2 mg daily, and topiramate 25 mg daily. She was never treated for hepatitis. Delivery of her child the following month was uncomplicated, but she did require a second epidural injection during labor. After birth of her child, she had persistent headaches that were suspected to be secondary to a cerebrospinal fluid leak. She underwent epidural blood patch to treat the suspected leak, but her symptoms did not resolve. She began having shooting pain in her back that radiated into her legs. She described the headache as generalized, dull, nonradiating, and constant with a gradual onset that "worsen with laying down or standing up" and endorsed accompanying photophobia. She had papilledema with diplopia, mild bilateral cranial nerve VI palsy, and decreased visual acuity. At this point, she was seen by ophthalmology and was admitted to the hospital. A lumbar puncture (LP) showed mildly elevated nucleated cell count of 179 with 50% PMNs, 42% lymphocytes, and 6% monocytes. Glucose was low at 36 mg/dL (serum glucose was 92 mg/dL) and protein was elevated at 287 mg/dL, consistent with a meningitis process and suggestive of bacterial meningitis. However, her CSF cultures were negative for histoplasma, tuberculosis, AFB, Cryptococcus, cytospin, fungus, and viruses. Additional testing showed HIV negativity, hepatitis A and C positivity and negative serology for listeria, Brucella, VDRL, syphilis, and lyme. Her general chemistry panel on admission and throughout her hospital stay was normal. Liver function tests, CRP, IgG, and thrombocyte count were unremarkable. She was negative for antinuclear antibody, anti-LA/anti-RO, and antineutrophil cytoplasmic antibodies. Her CRP was normal with a mildly elevated ESR at the time of presentation in April, consistent with a largely resolved inflammatory process. MRI studies showed diffuse leptomeningeal enhancement of the distal spinal cord, conus medullaris, and nerve roots of the cauda equina extending beyond the neural foramina bilaterally in T1 contrasted images [Figures 1 and 2]. The nerve roots were displaced laterally in the distal thecal sac. The dura appeared thickened and avidly enhanced from L5 to S2 and there was a fluid-fluid level appreciated on the T2-weighted sequences suggesting possibly proteinaceous debris, blood, or pus [Figure 3]. The DWI image showed marked restriction from L4 to L5 through the S2 levels [Figure 4]. Infectious disease was consulted and suggested chronic neutrophilic meningitis in the setting of an underlying autoimmune/inflammatory condition given the nature of her pain and her complicated medical history. She was discharged after 1 week on methylprednisolone (1 g/day for 5 days) that resulted in a near resolution of her back pain, headaches, and vision changes except for when she missed doses. She had no fevers, chills, or night sweats but reported a 10 lb weight loss with poor appetite. Her steroids were tapered to 50 mg, daily and when the dose was tapered, she had symptom return. Infectious disease continued following and a lack of resolution of her pain prompted additional screening. Repeat MRI at a month post-partum showed no significant changes from the previous scan and continued leptomeningeal enhancement of the distal spinal cord and cauda equina nerve roots consistent with arachnoiditis. Her second LP showed a worsening inflammatory picture with 2682 nucleated cells (94% PMNs), low glucose at 26, elevated protein at 297, and 13 bands. The patient's WBC was elevated at 23.2 from 16.4 three months prior although she remained afebrile. Her back pain rating at this time was 6-7/10. Given her persistent symptoms and lack of diagnosis, she was scheduled for an L5-S1 laminectomy for an intradural tissue biopsy. During surgery, cultures were taken at every level of the exposure. After the laminectomy was complete, the epidural space appeared normal, but the dura was thickened and difficult to open inferiorly. The dura incision was carried cranially and once the subarachnoid space was entered, a copious amount of white, soft purulence material was released. The nerve roots were adherent to surrounding dura and to each other. There were no obvious signs of a capsule; however, the infection was likely loculated based on its appearance and indolent course. The intradural compartment was irrigated until the CSF ran clear. There were no intraoperative complications and she was started on postoperative antibiotics, including 500 mg metronidazole q8 h, 1 g vancomycin q12 h, IV fluconazole 400 mg, daily, and 2 g cefepime q12 h. After the procedure, the patient remained afebrile, without aberration in vitals, and was ambulatory. The histology showed rare nonseptate pseudohyphae and blastospores without a broad-based bud, indicative of a Candida species [Figure 5]. The submitted tissue was necrotic and demonstrated local inflammation on pathologic examination [Figure 6]. Microbiology cultures from the abscess grew colonies of C. dubliniensis. No other organisms were isolated or seen under various other staining modalities and multiple cultures taken from the abscess all grew only C. dubliniensis and no other organisms. This was a pan-sensitive microbe with low minimum inhibitory concentrations to caspofungin, fluconazole, and voriconazole of 0/25, 1.0, and 0.012 mcg/mL, respectively. Cefepime, metronidazole, vancomycin, and IV fluconazole were discontinued and the patient was started on 400 mg fluconazole PO daily (rather than outpatient peripherally inserted central catheter due to IV drug abuse) for a planned minimum of 4 weeks. After surgery, she endorsed only mild low back pain at the incision site and with position changes. At 3-week postoperative follow-up, her back pain was worsening and the operative site was infected with induration of the surrounding skin but remained afebrile. She reported a significant amount of purulent drainage produced from her incision, which resulted in improvement of her symptoms. She was started on cephalexin. She is currently scheduled for follow-up with infectious disease and for a repeat MRI of her lumbar spine. Of note, throughout the patient's entire hospital course and at her follow-up appointments, she remained without neurological deficit. Her mental status examination, cranial nerves, strength, sensory perception, coordination, and reflexes were all within normal limits and without significant change at any time point.

candida dubliniensis, cauda equina, intradural abscess, spinal abscess

PMC9626225_01

Female

We present a 64-year-old Caucasian female with 35 pack-year smoking history and no comorbidities who initially presented to an outside facility due to acute left upper quadrant abdominal pain. She was eventually diagnosed with acute left adrenal hemorrhage, transfused packed red blood cells (PRBC), and underwent embolization of the left adrenal artery. She was later discharged to follow up with her PCP. A few days later, she presented to our hospital with complaints of shortness of breath (SOB) with exertion. The patient reported a three-week history of SOB prior to presentation, which worsened following the recent hospital discharge. She was hemodynamically stable upon presentation. Physical examination was significant for generalized pallor, jaundiced mucosa, and a large hematoma surrounding the left flank. The patient's hemoglobin on presentation was 7.5 (7.2 at discharge from the previous hospital). She also had severe orthostatic hypotension. Her other labs include urea 16, creatinine 0.89, sodium 136, potassium 4, AST 90, ALT 62, ALP 69, total bilirubin 3.4, WBC 7.6, platelets 97000, and cortisol > 20. Her chest X-ray revealed a small pleural effusion on the left, which was initially thought to be a sympathetic effusion from underlying hematoma. CT Angiogram of abdomen and pelvis revealed evidence of coiling of the left adrenal gland with a 6 cm mass likely representing hemorrhage in the left adrenal gland itself. There was a hemorrhage in the adjacent pararenal space crossing the midline in the retroperitoneum in the right paracolic gutter without evidence of active bleeding. She was admitted for further workup of her progressively worsening symptoms and etiology of the adrenal hemorrhage. Despite adequate volume resuscitation with PRBC and IV fluids, the patient remained symptomatic with no significant improvement in blood count. A repeat chest X-ray was obtained which revealed worsening of the pleural effusion, hence the patient underwent thoracentesis which revealed bloody exudative effusion (>2 million RBC) but cytology did not reveal malignant cells. Due to high suspicion of ongoing malignancy, repeat imaging was obtained. CT abdomen and pelvis revealed worsening left hematoma with additional new right adrenal hemorrhage (Figures 1 and 2). CT chest revealed scattered lymphadenopathy in the left supraclavicular neck, bilateral axilla, and left hilum with questionable metastatic adenopathy, along with a small indeterminate 5 mm left upper lobe pulmonary nodule. MRI of the brain revealed multiple scattered tiny foci concerning a metastatic disease. Eventually, the patient underwent an excisional biopsy of the right axillary lymph node, with the hope of identifying the primary tumor. While awaiting pathology reports, we also ruled out tuberculosis with QuantiFERON Gold and autoimmune etiology with an extensive workup. The plan was to evaluate the extent of the disease with imaging once pathology was available, and plan cancer treatment accordingly. Unfortunately, the patient clinically deteriorated due to the development of disseminated intravascular coagulation (DIC). Her renal function worsened due to acute tubular necrosis related to DIC, intravascular volume depletion, and hypotension. Mentation gradually deteriorated due to uremic encephalopathy, and renal replacement therapy was planned. Following vascular catheter insertion, the patient had a large pneumothorax with hemodynamic compromise and had to be transferred to the ICU. Despite the reversal of the pneumothorax, her hemodynamics did not improve with vasopressor refractory shock and the patient succumbed to death. We received the final pathology result after her demise as "Poorly differentiated adenocarcinoma, primary lung cancer."

PMC6219105_01

Male

A healthy 17-day-old male infant without a family history of immunodeficiency syndrome was consulted by his family physician for cough, nasal discharge, and a fever on the third day of illness. He had not started any vaccines because of his age (<1 month). He was diagnosed with acute pharyngitis along with exudation on the back of the larynx. Although cefotaxime treatment was initiated, wheezing, difficulty in vocalizing, and cyanosis on crying were observed on the fourth day. On the fifth day, laryngoscopy revealed a downward spread of exudation and laryngeal edema, which led to diagnosis of acute epiglottitis (Figure 1A, B). Because airway management was required, he was referred to our pediatric intensive care unit and immediately started on artificial respiration. At the time of admission, the patient's laboratory tests showed the following: white blood cell count 4,700/muL (band cell: 35%, segmented cell: 31%, eosinophil: 5%, monocyte: 8%, lymphocyte: 18%, atypical lymphocyte: 3%), hemoglobin level 11.1 g/dL, platelet count 24.4x104/muL, and C-reactive protein level 6.65 mg/dL. Other laboratory findings were as follows: serum albumin 2.4 g/dL, total bilirubin 0.48 mg/dL, sodium 137 mEq/L, potassium 3.3 mEq/L, aspartate aminotransferase 14 U/L, alanine aminotransferase 8 U/L, lactate dehydrogenase 260 IU/L, urea nitrogen 3.9 mg/dL, and creatinine 0.19 mg/dL. His IgG, IgA, IgM, C3, C4, and CH50 levels were within the normal ranges (IgG: 686 mg/dL, IgA: 19 mg/dL, IgM: 52 mg/dL, C3: 84 mg/dL, C4: 15 mg/dL, and CH50: 32.5 U/L). His arterial blood gas under 1.0 of the fraction of inspired oxygen showed a pH of 7.428, pCO2 of 42 mmHg, pO2 of 114.0 mmHg, HCO -3 of 27.2 mmol/L, and base excess of 3.1 mmol/L. Rapid antigen test for respiratory syncytial and adenoviruses was negative (Capilia RSV Neo and Adeno; TAUNS Laboratories, Inc., Shizuoka, Japan). MRSA was detected from the posterior nasal cavity swab culture and the pharyngeal swab culture at the site attached to the exudate, but skin swab culture and blood culture were negative. Owing to the detection of MRSA, he was treated with vancomycin. The fever disappeared on the first day of admission, and he was extubated on the eighth day of admission. Figure 1C, D shows his laryngoscopic images after extubation. Finally, the patient was discharged on the 18th day of admission. Gram staining and culture using blood and chocolate agar were performed to identify the organisms using swabs obtained from the posterior nasal cavity or pharynx of the patient. Because Sta. aureus was detected, the culture using MRSA screen media (CHROMagar ; Kanto Chemical Co., Inc., Tokyo, Japan) was performed to identify MRSA. Determination of the minimum inhibitory concentration of each antibiotic for the isolated strain was performed using a RAI-SUS system with the RSMSE panel (Nissui Pharmaceutical Co., Ltd, Tokyo, Japan). The inoculum was adjusted to yield a cell density of 1x105 colony-forming units/mL. The plates were incubated for 18-24 hours at 35 C and then analyzed automatically. Result of the antimicrobial susceptibility test for the isolated strain is shown in Table 1. Bacterial genomic DNA of the isolated strain was extracted using a DNeasy Blood & Tissue Kit (Qiagen) with lysostaphin (Wako). Genomic DNA was used as a template for PCR-based screening assays. MRSA SCCmec type (I-V) screening was conducted using a PCR-based assay as previously described. We detected mecA gene and class B mec gene complex and type 2 ccr gene complex by multiplex-PCR methods. These results indicated that SCC-mec type of the isolated strain was type IV. Staphylococcal virulence genes including the Panton-Valentine leukocidin (PVL) gene (luks-pv), two exfoliative toxin (ET) genes (eta and etb), and toxic shock syndrome toxin 1 (TSST-1) gene (tst-1) were detected by PCR assay using primers that have been reported previously. The results of the MRSA genome analysis of the patient sample revealed a PVL-negative and TSST-1-positive SCCmec type IV clone (Table 2).

panton-valentine leucocidin, exudate, pre-haemophilus influenzae type b vaccine era, toxic shock syndrome toxin 1, type iv clone of staphylococcal cassette chromosome mec

PMC7700053_01

Male

The patient was a 35-year-old Indian male with no significant medical history. He was born in Tamil Nadu, India, and emigrated to Singapore six years prior to presentation. He returns to India annually to visit friends and relatives, both in small towns and villages in rural areas with farms housing farm animals. He drank well water and ate local food during these trips back to India. He had no known personal or contact history of tuberculosis. He presented to medical care after a first-onset seizure which was witnessed by his wife. The seizure was described as jerking movements of all four limbs, associated with uprolling of eyeballs, and a transient loss of consciousness lasting ten minutes. There were no preictal symptoms. Postictally, he was drowsy for another ten minutes and was unable to recall the events upon regaining consciousness. Prior to this seizure, he was generally well and did not report any constitutional symptoms such as fever, night sweats, weight loss, or anorexia. On examination, he had a low-grade temperature of 37.8 degrees centigrade. Blood pressure, heart rate, and oxygen saturation were normal. Neurologic examination did not reveal any focal neurologic deficits, and there were no localising signs of infection. Laboratory investigations were significant for leukocytosis with a white blood cell count of 18.4 x 109/L. There was no peripheral eosinophilia. Renal and liver function tests were normal, as were routine biochemistry and serum electrolytes. Noncontrasted computed tomography scan of the brain revealed an ill-defined eight-millimetre hypodense lesion with a hyperdense rim in the left basal temporal region, with mild surrounding vasogenic edema. MRI of the brain further delineated this as a solitary ring-enhancing lesion measuring 1.2 by 1 centimetre (Figure 1). Postcontrast images showed thick smooth peripheral enhancement, but no clearly-defined scolex or mural nodule consistent with a typical viable cyst of neurocysticercosis. Skull base artefacts limited assessment of the contents on diffusion-weighted images. Human immunodeficiency virus serology was nonreactive. Two sets of blood cultures were negative, as was serum Cryptococcal antigen. Three sets of stool microscopy for ova, cyst, and parasites did not pick up any parasites. As there was no available serologic test for cysticercosis at our centre, a serum sample was sent to an overseas reference centre for serologic testing with an antibody-detecting ELISA-based assay. After discussion with the managing neurosurgical team, the patient opted for brain biopsy for definitive diagnosis, in view of the broad range of differential diagnoses based on the neuroradiologic features. A left minicraniotomy was performed and identified a slightly hardened pale white to yellow lesion, with a milky white exudate upon breaching the lesion capsule. The entire cyst was excised and sent for histology and microbiologic evaluation. Histology demonstrated granulomatous inflammation featuring aggregates of epithelioid histiocytes and multinucleated giant cells lining the fibrous cyst wall, accompanied by a mixed inflammatory infiltrate and necrosis. Features characteristic of a cysticercus were absent, and no viable larva was identified (Figure 2). No fungi or acid-fast bacilli were found on Gomori methenamine silver (GMS) and Ziehl-Neelsen histochemical stains, respectively, and no Toxoplasma organisms were identified on immunohistochemical staining. Microbiologic testing did not identify causative organisms on Gram stain, aerobic and anaerobic culture, fungal smear, acid-fast smear, and GeneXpert MTB/RIF assay (Cepheid Inc, Sunnyvale, CA, USA). In view of nonspecific histologic and radiologic features, no definite diagnosis was made at this point. As histology showed granulomatous inflammation, and tuberculosis is endemic in the region, empiric combination ant-tuberculous therapy and a tapering corticosteroid regimen were initiated after discussion and shared decision-making between the patient and medical team while awaiting further diagnostic tests. While awaiting ELISA serologic assay results, which later returned positive for cysticercosis, residual brain tissue was sent to the National Public Health Laboratory, a tertiary reference laboratory, for further molecular diagnostic testing. 25 milligrams of brain tissue was minced on dry-ice, lyzed in ATL buffer with proteinase K, and DNA was extracted using QIAmp DNA Mini Kit (Qiagen, Hilden, Germany) according to the manufacturer's instructions. A Taenia solium-specific PCR targeting the pTsol9 repeat element based on a previous paper by Almeida and colleagues and a pan-Cestoda PCR targeting a fragment of the mitochondrial ribosomal RNA (16S rRNA - 12S rRNA) genes based on a paper by Le and colleagues were attempted. Capillary electrophoresis on QIAxcel Advanced System (Qiagen, Hilden, Germany) equipped with DNA Fast Analysis Kit displayed multiple bands of expected sizes (120 bp, 280 bp, and 440 bp), corresponding to the amplification of 1, 2, and 3 repeat unit(s) of the pTsol9 element, respectively (Figure 3) and a single band of 810 bp for the 16S rRNA-12S rRNA genes. Purification, bidirectional Sanger sequencing, alignment, and cross-checking of the sequences were performed as previously described for the 16S rRNA-12S rRNA PCR products. A consensus fragment of the 16S rRNA-12S rRNA genes (808 bp) was obtained, compared by Basic Local Alignment Search Tool (BLAST) against GenBank (NCBI, Bethesda, MD, USA), showed 99.6% similarity (805/808) with sequence [AB086256], and thus ascertained that detected DNA was from T. solium. The sequence has been deposited in GenBank under the accession number (MT772182). Upon molecular confirmation of neurocysticercosis, antituberculous therapy was stopped. The patient completed 14 days of oral albendazole together with a rapid taper of corticosteroids and has remained well since on subsequent follow-up.

PMC6582892_01

Female

A 75-year-old woman from Ghana with medical comorbidities of hypertension (not on an ACE inhibitor) and chronic cough was referred to our gastroenterology (GI) clinic for management of suspected gastroesophageal reflux disease (GERD) as the cause of chronic cough. As per the patient, she had been having a chronic cough for more than ten years. The cough was nonproductive, without any aggravating or relieving factors. She had reported postprandial heartburn. She recalls that cough started before her heartburn. She reported using albuterol and proton pump inhibitors (PPIs) without improvement in her cough. She did notice some improvement in her heartburn. She had never smoked, and her PPD was negative. There was no prior or current occupational exposure or pet exposure. She underwent extensive otolaryngology evaluation including a laryngoscopy that showed evidence of chronic laryngopharyngeal reflux. She had been evaluated by pulmonologist and underwent spirometry, imaging studies, bronchoscopy, and fractional exhaled nitric oxide (FENO) testing and all the test results were normal. She had been prescribed various therapies including oral, nasal, and inhaled corticosteroids, montelukast, and proton pump inhibitors without any improvement in cough. Because of her typical GERD symptoms, she had a 48-hour Bravo pH testing done in 2011. The study revealed 4.9% of the time with pH below 4 and a total of 106 reflux episodes consistent with GERD. She was evaluated for the surgical intervention, and as a preoperative work-up, high-resolution esophageal manometry was performed. The manometric finding consistent with GERD revealed a hypotensive lower esophageal sphincter (LES). Subsequently, the patient underwent laparoscopic Nissen's fundoplication in 2012. After fundoplication, she was symptom-free. However, in few months her cough recurred but absence of heartburn and overt acid reflux symptoms was intriguing. She again sought evaluation for cough. She underwent EGD and Bravo pH testing in 2013. There was no evidence of esophagitis and the endoscopic evidence of the fundoplication was appreciated. The ambulatory pH test revealed 0.1% of total acid exposure time and no symptom correlation. She had moved to Ghana for a brief period and did not seek any medical attention. She continued her PPI with no significant improvement. Gastroenterology consultation was sought again as the cough persisted. The physical examination including vital signs was unremarkable. She underwent a repeat Bravo pH study in February 2018 that revealed zero acid exposure and the study was not consistent with GERD (Figure 1 and Table 1). Subsequently, a high-resolution esophageal manometry was done in April 2018 with the findings indicating ineffective esophageal motility (Table 2). A second opinion was sought from the gastrointestinal motility expert for the medical management of ineffective esophageal motility disorder. Given the absence of dysphagia, she was not considered a good candidate for medical management. To rule out nonacid reflux as a possible etiology of recurrent cough, patient was offered 24-hour Multichannel intraluminal impedance (MII) assisted pH monitoring. However, given the chronic cough and nasal discomfort, patient declined further intervention. Repeat laryngoscopy revealed laryngeal edema. To better assist with esophageal clearance, she was recommended to take frequent sips of water. She was suggested to carry a water bottle and take 1 to 2 sips of water every 15 minutes. Subsequently, patient presented to our clinic for a follow-up visit and was excited to report that her cough after years of work-up and medication use had finally subsided. She reported compliance with frequent sips of water. Patient had multiple interval follow-up for next 6 months where she reported continued absence of cough with multiple sips of water during the day.

PMC10182765_01

Female

A 27-year-old young adult Ethiopian female patient who is known to have chronic rheumatic valvular heart disease for the past 8 years started to experience repetitive uncontrollable movements of her extremities and trunk since 3 years ago and which were occurring once to three times per month. The abnormal body movements usually lasted up to a week duration and got worse while she tried to sit or walk and improved with rest. She was consistently taking intramuscular injection of benzathine penicillin G 1.2 million units every month for the past 8 years. She did not have previous history of behavioral and emotional lability. She does not remember childhood history of rheumatic fever or movement disorder. She did not use oral or injectable hormonal agents. There was no family history of rheumatic fever, social stress, psychiatric disease, or tic disorders. Upon physical examination, temperature was 36.7 C, heartbeat was 90 beats per minute, and blood pressure was 100/70 mmHg. There was holosystolic murmur at the apical area radiating to the left axilla. Choreiform movements were apparent on all limbs and trunk. Laboratory investigations revealed moderate leukopenia (but with a normal repeat complete blood count after 3 days), normal liver enzymes, normal renal function tests, erythrocyte sedimentation rate of 37 mm/hour, negative qualitative C-reactive protein, weakly positive anti-streptolysin O antibody, negative qualitative antinuclear antibody, negative urine human chorionic gonadotrophin and normal level of thyroid stimulating hormone. Magnetic resonance imaging of the brain showed left parietal periventricular tiny white matter non-specific lesion. Rheumatic heart involvement was confirmed by echocardiography which showed thickening of mitral valve leaflets with severe mitral regurgitation (Figure 1). The present case was diagnosed as recurrent Sydenham chorea based on clinical evidence and she was prescribed valproic acid 500 mg PO/day for 2 weeks and benzathine penicillin G injection was made every 3 weeks. She was re-evaluated after 2 weeks and she had significant improvement with good control of motor activity and reduced involuntary movements of her extremities and trunk. She was then followed every 3 weeks for the subsequent 3 months and she did not have any abnormal body movement. She was finally referred to an advanced cardiac center for possible mitral valve replacement.

sydenham chorea, recurrence, rheumatic fever

PMC9755212_01

Male

A 42-year-old Italian patient with a 20-year history of plaque psoriasis and psoriasis arthropathica presented to our hospital with numerous ulcerations or nodules within his psoriatic lesions that had appeared 6 months earlier. He had been treated with subcutaneous methotrexate (25 mg per week) for the past 9 years and adalimumab (40 mg every other week) for the past 7 years. Topical treatment included halometasone 0.05% plus triclosan 1% cream and calcipotriol plus betamethasone dipropionate foam in the weeks before hospitalization. The obese patient (BMI 39 kg/m2) showed multiple psoriatic lesions characterized by erythemato-squamous plaques disseminated over the integument (PASI 16.6). Moreover, the patient showed erosive and partly ulcerating plaques and nodules, some of them covered by distinct brown crusts, at the right forearm, right knee, left flank and the abdomen (Figures 1A,B). Physical examination showed no pathological findings. There was no lymphadenopathy. The histopathology of an externally performed lesion biopsy reported dermal T-cell infiltrates without evidence repeated of malignancy. Two repeat biopsies and histologies from morphologically different lesions on the right forearm and right flank revealed an interface dermatitis with pseudolymphomatous infiltrates, thickening of the epidermis, follicular hyperparakeratosis, and perivascular, periadnexal, superficially accentuated lymphocytic infiltrates with a preponderance of T cells (Figures 2A,B). Tissue clonality analyses demonstrated polyclonal IgH and TCR gamma chain gene expression, thus excluding lymphoma. Direct immunofluorescence did not detect any IgG, IgM, IgA, or C3 depositions. Syphilis serology, carried out due to numerous plasma cells in the tissue, yielded negative results. Moreover, an HIV infection, borreliosis and tuberculosis were ruled out by negative antibody or PCR tests. A serum sample was negative for antibodies against (extractable) nuclear antigens. Complement factors were within normal ranges. In hematoxylin-eosin (Figure 1C), Giemsa (Figure 1D) and Feulgen stains, intracellular Leishmania amastigotes with kinetoplasts were seen, which were identified by culture, miniexon PCR and restriction fragment length polymorphism-analysis as L. infantum. The patient also had a positive anti-Leishmania serology (maximum titer detected by indirect immunofluorescence using viable L. major promastigotes was 1:1,600). Since the patient originated from and repeatedly visited southern Italy, it is likely that he acquired the infection during his temporary stays. The therapy with adalimumab was stopped, while treatment with methotrexate was continued (Figure 2). Interestingly, the ulcerations already started to heal under intensive topical treatment with salicylic acid, dithranol, and clobetasol propionate 0.05% ointment. Visceral involvement was excluded based on clinical parameters and sonography of liver and spleen. Therefore, we pursued a watch-and-wait strategy without specific therapy for leishmaniasis. The ulcerative skin lesions, which were clinically compatible with cutaneous leishmaniasis, completely regressed. After switching the systemic treatment to secukinumab (anti-IL-17A) or apremilast, the psoriatic lesions remained unaltered, but finally improved with ixekizumab (anti-IL-17A). During regular medical follow-up for almost 5 years the clinical condition of the patient remained stable (Figure 3).

adalimumab, anti-tnf therapy, cutaneous leishmaniasis, skin pseudolymphoma, skin ulceration

PMC7728662_01

Male

A 57 year-old Chinese man with the complaint of a dry cough for more than 1 month was admitted to the Department of Thoracic Surgery. The patient had a smoking history of over 20 years, smoking two packs per day, and several years' history of hemorrhoids. He had not undergone any surgery before and had no family history of tumor. His physical status score was 0. The chest CT scan on October 9th, 2019 showed a soft tissue shadow on his left lower lobe and a left hilum space-occupying lesion (Figure 1). The masses were consistent on CT imaging, indicating that the one next to the left hilum was an enlarged hilum lymph node. The CT scan also showed an inflammatory lesion and obstructive lesion on the left lower lobe (Figure 1). PET-CT scan on October 9th, 2019 indicated a dorsal segment soft tissue mass on the left lower lobe adjacent to the hilum, with a size of 3.6 cm x 5.2 cm x 4.8 cm and an SUVmax of 25.3, and a basal segment soft tissue mass, with a size of 3.8 cm x 3.6 cm x 3.8 cm and an SUVmax of 12.5 (Figure 1); the masses had an increased metabolic rate and were considered to be malignant lesions. Multiple mediastinal and right hilum lymph nodes were detected with an increased metabolic rate; the lymph nodes were considered to be inflammatory lesions. Otherwise, no distant metastatic signs were exhibited on PET-CT. No abnormal signs were observed on brain MRI, either. The patient underwent needle biopsy on October 12th, 2019 and the pathologic result showed poorly differentiated squamous carcinoma. The patient refused to take any invasive examinations after needle biopsy, thus mediastinal staging was not performed. The specimen was sent for PD-L1 detection and tumor proportion score (TPS) was 80%, indicating a high expression of PD-L1. Thus, the clinical staging for this patient was cT2aN1M0, IIB according to the 8th edition lung cancer stage classification system. Because of the enlarged lymph node proximal to the hilum, the surgery plan was considered to be pneumonectomy. Thus, in order to reduce the size of the tumor and preserve residual lung function, this patient received neoadjuvant chemotherapy (gemcitabine 1.6 g, d1, d8 plus cisplatin, 60 mg, d1, d2, Q3W). The chemotherapy plan was implemented for five cycles from October 17th, 2019 to March 17th, 2020 and pembrolizumab (200 mg, d1, Q3W) was added from the second cycle. Due to the outbreak of COVID-19, the plan had to be suspended after the fourth cycle. The fifth cycle was initiated on March 17th, 2020. The CT scan on December 6th, 2019 after two cycles of neoadjuvant therapy and March 15th, 2020 after four cycles of neoadjuvant therapy showed shrinking masses on the left lower lobe (Figure 2). During the treatment, the adverse effects in this patient included vomiting, thrombocytopenia, and occasional chest distress. The platelet count of the patient was 61.00 x 109/L on October 31st, 2019. All the symptoms were alleviated after symptomatic treatment. The PET-CT scan on April 28th, 2020 showed the mass adjacent to the hilum on the left lower lobe to be 1.7 cm x 2.3 cm x 2.0 cm, with the SUVmax being 8.4 (Figure 3). The mass on the basal segment was 1.7 cm x 1.8 cm x 1.6 cm, with an SUVmax of 8.4 (Figure 3). Finally, the patient underwent left lower lobectomy on April 30th, 2020 and the intraoperative pathologic report showed a benign lesion of the left lung nodules and no tumor in the resected lymph nodes. The postoperative pathologic result indicated no detected tumor in the resected mass or the lymph nodes. Thus, the patient was evaluated as having a pathologic complete response (pCR). Postoperative follow-up of the patient was done on June 2nd, 2020, with no recurrent or metastatic signs on chest CT, cranial CT, abdominal ultrasonography, or urinary system ultrasonography. The patient refused postoperative chemotherapy for fear of its adverse effects and received intravenous injection of 200 mg pembrolizumab on June 7th, July 8th, August 3rd, and August 29th, 2020; reported adverse effects included mild cough, vomiting, and decreased platelet count (103.00 x 109/L on August 4st, 2020 and 83.00 x 109/L on August 29st, 2020), which were all alleviated automatically or after symptomatic treatment. Carbohydrate antigen 125 and carcino-embryonic antigen were 22.30 U/mL and 1.33 ng/mL on June 5th, 9.80 U/mL, 0.95 ng/mL on July 6th, 8.50 U/mL, 1.11 ng/mL on August 3rd and 7.90 U/mL, 1.43 ng/mL on August 28th, respectively. Further data were not available. Major events of this case were summarized in Figure 4.

pd-1/pd-l1, lung cancer, neoadjuvant therapy, pathological complete response (pcr), pembrolizumab

PMC10423897_01

Male

On 24 January 2022, a 37-year-old male office clerk presented to our hospital for investigation and management of muscle pain in the extremities with headache. The man used to be in good health and did not have the habits of smoking and alcohol. Five months prior to his admission, he began suffering from symmetry pain in the muscles of the limbs, accompanied by headache on the left side, without nausea, vomiting, or fever. Physical examination revealed body temperature of 36.4 C, heart rate of 76 beats per minute, and blood pressure of 117/69 mm Hg; marked tenderness in gastrocnemius, quadriceps and biceps brachialis. Cardiovascular, abdominal, and neurological examination was unremarkable except for weakness and stiffness in the extremities. Blood chemistry tests revealed myositis marked by lactate dehydrogenase (LDH) of 695 U/L (normal range, 120-450 U/L), creatine kinase (CK) of 1955 U/L (normal range, 50-310 U/L), creatine kinase-MB (CK-MB) of 438 U/L (normal range, 0-24 U/L), myoglobin (MYO) of 900 U/L (normal range, 23-112 U/L). Preliminary etiological investigations excluded the presence of necrotizing autoimmune myopathy, cryptococcosis, tuberculosis, and toxoplasmosis, but Human immunodeficiency virus (HIV) RNA was positive (2.55x106 copies/muL). Subsequent flow cytometry showed the CD4+ T cell count is 6 cells/microL. Cerebral magnetic resonance imaging (MRI) revealed multiple parenchymal lesions with fine contrast enhancement in bilateral cerebral hemispheres, pons, medulla oblongata, and right cerebellar hemispheres, most of which are located in bilateral cerebral cortex (the large one can reach 15 mm in diameter) ( Figures 1A-D ). The MRI results suggested infectious lesions. A biopsy of right gastrocnemius was performed, and pathology showed infiltration of lymphocytes and neutrophils. Several scattered oval-shaped pathogens were observed by Gomori methenamine silver staining ( Figure 1E ) and fungal fluorescence staining ( Figure 1F ). To determine the a etiological agents, the gastrocnemius tissue and cerebrospinal fluid were subjected to metagenomic next generation sequencing (mNGS), respectively. Within 24 hours after receipt of the samples, 3 species of fungi, 6 species of bacteria, and 1 species of virus were detected in the gastrocnemius tissue ( Figure 1G ). Meanwhile, 1 species of fungi and 3 species of viruses were detected in cerebrospinal fluid sample ( Figure 1H ). Among these microbes, only T. hominis has been reported to cause myositis in immunocompromised patients. And T. hominis was identified in both gastrocnemius tissue and cerebrospinal fluid. Finally, the diagnosis of myositis and brain infection caused by the infection of T. hominis was made. During the hospitalization, he received tramadol to relieve his pain. After the T. hominis infection was confirmed, he initiated a 12-week course of oral albendazole (800 mg/d), a 5-day course of oral dexamethasone (5 mg/d), and regular antiretroviral therapy (Biktarvy). The patient was discharged after 6 weeks of treatment, when the myalgia was significantly relived, and the size and degree of brain lesions were improved ( Figure S1 ). Upon follow-up in 2 weeks, the muscle pain and headache were completely recovered. After the 12-week course of treatment, mNGS showed that his cerebrospinal fluid was negative for T. Hominis ( Figure 2 ).

mngs, trachipleistophora hominis, brain infection, microsporidia, myositis

PMC8278846_01

Male

An HIV-exposed uninfected 20-month-old boy presented to Chris Hani Baragwanath Academic Hospital in Johannesburg, South Africa, with a 2-day history of shortness of breath, cough and noisy breathing. He had also experienced night sweats, fever and vomiting for a week. Two weeks prior to this presentation, he had been diagnosed with bacteriologically unconfirmed PTB at a primary healthcare clinic and was empirically started on a four-drug antituberculosis treatment regimen (rifampicin, isoniazid, pyrazinamide and ethambutol). The diagnosis was based on a chest X-ray (Fig. 1A) and a positive Mantoux test. His father (a household contact) had been diagnosed with PTB, and had been on first-line antituberculosis treatment for 4 months. The boy had had normal growth and development up to 1 year of age, but had subsequently lost weight, and fallen from a weight-for-height z-score +2 to the median over the preceding 8 months. On admission, he was apyrexial, tachycardic and in moderate respiratory distress, with oxygen saturations of 97% in room air. He had marked chest wall indrawing and bilateral posterior cervical and axillary lymph nodes (<0.5 cm in diameter). He was clinically hyperinflated, with bilateral wheezing. The rest of his clinical examination was normal. He was diagnosed with viral bronchiolitis, and therefore a chest X-ray was not performed. He was started on oxygen and hypertonic saline nebulisation. He responded poorly to this initial treatment and was therefore started on oral corticosteroids and amoxicillin on day 2 of hospitalisation, and his first-line antituberculosis treatment was continued. Gastric aspirate samples for microscopy for acid-fast bacilli, Xpert MTB/RIF (Cepheid, USA) and culture for mycobacteria were negative. During his hospital admission period his wheezing persisted, and he remained in moderate respiratory distress. On the fifth day of admission, he developed percussion dullness and absent breath sounds over the right hemithorax. A chest X-ray at this point revealed a large right-sided pleural effusion (Fig. 1B). A computed tomography scan of the chest revealed hilar lymphadenopathy and a large right-sided pleural effusion. The thoracic duct could not be visualised. Diagnostic pleurocentesis confirmed a chylothorax. It was suspected that tuberculous lymph nodes had eroded the thoracic duct causing the chylothorax, and therefore a bronchoscopy was performed, which revealed caseating lymph nodes in the right main bronchus suggestive of TB, and 90% obstruction of the left main bronchus. The Xpert MTB/RIF (Cephaid, USA) test on a bronchoalveolar lavage specimen identified rifampicinresistant Mycobacterium tuberculosis. Gastric aspirates, pleural fluid and bronchoalveolar lavage samples were all smear-negative for acidfast bacilli and mycobacterial culture-negative. The chylothorax was managed with a low-fat diet (with additional medium-chain triglycerides), therapeutic taps for worsening respiratory distress and an octreotide infusion. The boy was commenced on multidrug-resistant TB (MDR-TB) treatment (amikacin, levofloxicin, ethionamide, terizidone, pyrazinamide, ethambutol and high-dose isoniazid) and oral steroids. For further management, he was transferred to a hospital dedicated to the care of MDR-TB patients. One month later, he showed marked clinical improvement, with almost complete radiological resolution of the chylothorax, and reduced hilar lymphadenopathy (Fig. 1C). The full case overview is shown in Fig. 2.

chylothorax, drug resistant tuberculosis, endobronchial tuberculosis, paediatric tuberculosis, tuberculosis

PMC7392866_01

Male

A 5-year-old male child, who was the firstborn of a non-consanguineous marriage, was diagnosed with a seizure disorder and neuroregression as a post encephalitis sequel. He presented at the physiotherapy department with an inability to stand and walk. He was able to hold neck, roll, and maintain sitting with support. The patient was delivered by cesarean section, cried immediately after birth, and weighed 2 kilograms. He achieved age-appropriate developmental milestones in the first year of life. On his first birthday, he performed unsupported standing, took a few steps without the support and spoke 2-3 meaningful words. At 13 months of age, he had an episode of fever. After 24 hours, he experienced convulsions and was referred to a tertiary care centre by a local practitioner. He was admitted to PICU for 15 days with a high-grade fever of 106 degrees F and refractory status epilepticus. He was afebrile after day 3 of admission, and seizures continued till day 6. At the time of discharge, he had a frequency of 10 seizure episodes per day. He had neuroregression in all domains of development. He was unable to hold neck or roll, unable to speak, and unresponsive to any visual stimulus. He was discharged with anti-epileptic medications and a home exercise program. On evaluation, his Gross Motor Function Classification System (GMFCS) was at level IV, and Pediatric Balance Scale (PBS) score was 5. He had generalized hypotonia, preferred W-sitting, had tightness of bilateral hamstrings and calf muscles, displayed body rocking and chewed the clothes. Child neither made eye contact nor, was there visual fixation and tracking. His light perception was equivocal. Figure 1 and Table 1 shows the Magnetic Resonance Imaging (MRI) findings of the brain and the timeline of the events, respectively. Diagnostic assessment: GMFCS and PBS were used to measure gross motor function and balance, respectively. Diagnostic challenges: visual and cognitive impairment posed challenges. Furthermore, the child continued to have seizures 3-4 times per day. Physiotherapy intervention: the patient received regular physiotherapy based on the principles of neurodevelopmental treatment (NDT) and sensory integration (SI). The initial phase of 3 months included sustained stretching of the bilateral calf and hamstring muscles in functional positions, using unstable surfaces (equilibrium board and swiss ball) to challenge his sitting balance, using swing system to impart vestibular input, using visual stimulus to initiate a response, facilitating transitions like supine to sit and sit to stand by appropriate therapist s hand placement, providing proprioceptive stimulus by bouncing on a trampoline with support, weight-bearing exercises, joint compressions and use of a chewy tube. As the child regained the ability to sit and stand without support, walker (rollator) was used as a walking aid. The parents were educated about the home exercise program. During the follow-up visits interspersed over 2 years, the patient was reassessed and the exercise plan was modified accordingly. The child started taking a few steps without support. In the second phase of regular physiotherapy for 6 months by a physiotherapist, the goal was to achieve unsupported walking under supervision in the view of visual impairment. Sessions included standing on equilibrium board and stability disc with just as much support as required. Walking on compliant surfaces, ramp, uneven terrain and across obstacle course was practiced. Negotiating stairs holding onto the railing with moderate assistance was included. Proprioceptive, vestibular and visual inputs were continued to be given. Outcomes: after the course of physiotherapy, the child was able to sit and stand without support. He was able to walk without support on uneven surfaces under standby supervision. He started responding to light. He seemed to be avoiding bumping into objects or persons by apparently improved visual ability. Body rocking and chewing on clothes were seldom observed. Improvement in functional activities led to an increase in the participation of the child in social gatherings. Figure 2 shows the functional abilities of the child at the age of 5 years and 8 years, respectively.

post encephalitis sequelae, neurodevelopmental treatment, sensory integration

PMC7381944_01

Male

A 37-year-old previously healthy Sri Lankan male pharmacist presented to a tertiary care hospital with 8-day history of intermittent high spiking fevers. He has developed frequent small amounts of watery loose stools for the similar duration but denied blood and mucus in stools or associated abdominal pain or tenesmus. He did not have cough, hemoptysis, dysuria, or headache in systemic inquiry. He described feeling unwell for a last one-month period with significant loss of appetite and weight loss of 6 kg over the 1-month period. He did not have any chronic medical illness such as diabetes mellitus, hypertension, or dyslipidaemia. He denied a past history or a contact history of tuberculosis of a family member although he was exposed to many people as a pharmacist while dispensing medications. On examination, we found an averagely built male who is moderately pale, but not icteric. He did not have a clinically significant lymph node or thyroid enlargement. His pulse rate was 120/minutes with a blood pressure. He was tachycardic with a pulse rate of 120/minute and a blood pressure of 130/80 mmHg. His precordial examination revealed normal heart sounds with no murmurs. He was tachypnic, but lung examination was unremarkable. The abdomen was distended with mild tenderness in the right lower quadrant without hepatosplenomegaly. There was moderate amount of free fluid in the abdomen. His initial blood workup revealed a hemoglobin level of 9.5 g/dL, white count of 16 * 106/L (neutrophils 70%), and a platelet count of 560 * 106/L. His erythrocyte sedimentation rate is 120 mm in 1st hour, and C-reactive protein level is 290 mg/L. Alanine transaminase (ALT) level was 112 U/L, and aspartate transaminase (AST) level was 88 u/L. Alkaline phosphate level was 230 u/L. Serum bilirubin level was normal. Urine analysis was normal. Three blood cultures and a urine culture did not isolate any pathogen. Chest radiograph was normal. Two-dimensional echocardiogram revealed no murmurs or pericardial effusion. Peritoneal fluid analysis revealed 15 white cells/muL (80% lymphocytes), protein level of 2 g/dL, and LDH level of 190 IU/L. Peritoneal fluid was negative for acid fast bacilli. TB PCR of the peritoneal fluid was negative. The serum-ascites albumin gradient (SAAG) was 1.5 g/dL (serum albumin: 3.5 g/dL). CECT abdomen revealed a long thickened retrocecal appendix with minimal inflammation and moderate amount of free fluids (Figures 1 and 2). An explorative laparotomy was performed subsequently, and a mildly inflammed retrocecal appendix was found and removed. Microscopically acute inflammation was not present. Serosa and mesoappendix show numerous granulomata composed of epithelioid cells and Langerhans giant cells. Many show central spotty caseous necrosis (Figures 3 and 4). Initially, the patient was treated with merapenum, ofloxacin, and metronidazole for presumed gastrointestinal sepsis for 8 days until histology was available. Although he had a mild clinical response to antibiotics, he continued to spike fevers and inflammatory markers remained elevated. The patient was started on anti-tuberculous treatment (ATT) and a short course of oral dexamethasone. His anti-tuberculous treatment regime included isoniazid, rifampicin, pyrazinamide, and ethambutol in the intensive phase, and isoniazid and rifampicin combination to continue in the continuation phase. He made an uneventful recovery with marked clinical improvement following commencing of ATT. In two weeks of follow-up visit, he was well with a weight gain of 3 kg and inflammatory markers were normalized.

PMC7184841_01

Female

A 69-year-old caucasian woman was admitted to our hospital for the removal of giant dorsal haemangiomas. Multiple scattered cutaneous vascular lesions had emerged in recent years (Fig. 1) and prompted excision surgery before. There was also a medical background of immune thrombocytopenic purpura for more than 30 years, under long-term treatment with corticosteroids and immunosuppressants (cyclosporine and azathioprine), and multinodular goitre associated with hyperthyroidism. There was no history of smoking and besides the haemangiomas, there were no other lung, skin or constitutional symptoms. At admission, the platelet count was 75,000/muL (reference range [RR] 150-400); however, after the procedure, it dropped to 19,000/muL, and there was active bleeding from the surgical incisions. Methylprednisolone pulses were administered, and immunosuppressive therapy was maintained with the platelet count increasing to 47,000/muL and successful bleeding control. Nevertheless, during the following weeks, the patient's condition kept worsening with ascites and bilateral relapsing pleural effusion development. Paracentesis, thoracentesis, and bronchofibroscopies were performed, but although with characteristic exudative fluids, no pathological agents or malignant cells were ever identified. At this point, blood analysis showed Hb 7.6 g/dL (RR 11.5-16.5), white blood count 14.9 x 109/L (RR 4-11), platelet count 3,000/muL, D-dimers 35,923 mug/L (RR <500), fibrinogen 1.2 g/dL (RR 1.5-4.0), C-reactive protein 5.97 mg/dL (RR <0.30), FT4 3.02 ng/mL (RR 0.8-1.76) and TSH 0.006 mIU/L (0.55-4.78). Blood and urine cultures were positive for Enterococcus faecium. A diagnosis of disseminated intravascular coagulopathy (DIC) in a patient with KMS and sepsis was made. Immunoglobulin, methylprednisolone, plasma, and cryoprecipitate, together with broad-spectrum antibiotics were administered. Platelets stabilized at around 30,000/muL, but a consumptive state with marked weight loss and clinical worsening kept progressing. A full-body CT scan was performed with no evidence of tumours, lymphadenopathies, or bone lesions. After weeks, a Lowenstein-Jensen culture from bronchoalveolar lavage became positive for Mycobacterium tuberculosis. Standard antibacillary treatment was initiated; however, due to hepatotoxicity, the therapeutic scheme had to be readjusted. More than 4 months after admission, the patient was discharged on maintenance antibacillaries, corticosteroids, immunosuppressive therapy, and antithyroid drugs. Within 2 months she was readmitted due to an extensive left pleural effusion causing dyspnoea and respiratory insufficiency. Blood analysis showed Hb 10.1 g/dL, platelet count of 3,000/muL, alkaline phosphatase 196 IU/L (RR 50-136), GGT 308 IU/L (RR 5-55) and C-reactive protein 11.10 mg/dL. Although no bone lesions had been identified so far, a bone marrow aspirate was performed and showed only a reactive bone marrow without signs of pathogens or malignant cells. Active gastrointestinal bleeding eventually arose with the haemoglobin level dropping to 4 g/dL. Rescue therapy with rituximab was attempted with a platelet count increase to 42,000/muL and a D-dimer drop to 2,400 mug/L. Despite all the diagnostic and therapeutic efforts the patient died. A post-mortem examination revealed bone marrow infiltration by large cells with an irregular core and large cytoplasm (Fig. 2a, b). Immunohistochemistry was positive for CD1a, S100, and CD5, and negative for markers of plasmacytic, B- and T-cell differentiation (Fig. 2c). Electron microscopy identified Birbeck granules (Fig. 2d). The cause of death was established as LCH.

idiopathic thrombocytopenic purpura, intravascular disseminated coagulopathy, kasabach-merritt syndrome, langerhans cell histiocytosis, tuberculosis

PMC6243350_01

Female

A 45-year-old female was diagnosed with HIV infection in December 2013. She was started on highly active antiretroviral therapy comprising tenofovir 300 mg once daily (OD), lamivudine 300 mg OD and nevirapine 200 mg twice daily 5 months back, which she was tolerating well. Her CD4 count was 417 cells mul-1. She presented to us in June 2014 with pain in the right upper quadrant of 3 months duration that was intermittent, colicky, moderate in intensity and radiating to the infrascapular area, suggesting a biliary origin and requiring i.v. analgesics on multiple occasions. She also had low-grade fever, anorexia and weight loss of the same duration. There was no jaundice or other systemic features. Clinical examination revealed a 3-cm firm hepatomegaly; there was no peripheral lymphadenopathy and the rest of the clinical examination was unremarkable. Blood investigations suggested mild anaemia (Hb 10.2 g dl-1), elevated erythrocyte sedimentation rate (47 mm in the firsthour) and deranged liver function tests [serum bilirubin: 0.6 mg dl-1; albumin 4.0 g dl-1; aspartate aminotransferase 49 U l-1; alanine aminotransferase 145 U l-1; alkaline phosphatase 460 U l-1 (normal 42-128 U l-1)]. Ultrasonography of the abdomen showed mild central intrahepatic biliary radical dilatation with a dilated common bile duct (CBD) and multiple periportal and peripancreatic lymph nodes, the largest measuring 10 mm in diameter. Dynamic contrast-enhanced MRI and MR cholangiopancreatography were performed, which revealed a dilated CBD with an abrupt cut-off of the distal CBD with few subcentimetre lymph nodes (Figure 1). Mantoux test was positive with an induration of 25 x 25 mm at 72 h. Ultrasound-guided FNAC from periportal lymph nodes was performed with a 22-gauge spinal needle and two passes were obtained with the same needle on two separate occasions 1 week apart. However, on cytological examination, the aspirate was bloody and no conclusive diagnosis could be offered by the cytopathologist. 15 days after the second FNAC, the patient developed a painful skin nodule at the site of insertion of the FNAC needle. The nodule measured 1 x 1 cm and was erythematous, well-defined, firm and mildly tender, as shown in Figure 2 (indicated by arrow). FNAC tract seeding by tuberculosis was suspected and excision biopsy of the nodule was performed. Biopsy of the skin revealed many scattered, ill-formed epithelioid cell granulomas and Langerhans-type giant cells, and periappendageal and perivascular lymphohistiocytic infiltrate admixed with neutrophils and eosinophils. Ziehl-Neelsen stain for acid-fast bacilli was positive (Figure 3). The overall features were suggestive of tubercular granuloma. The patient was started on weight-based standard antitubercular therapy with four drugs (isoniazid 200 mg OD, rifampicin 400 mg OD, pyrazinamide 1 g OD and ethambutol 800 mg OD). On follow-up visits, the patient showed good clinical response:fever and pain had subsided, appetite had improved and there was gain in weight. Liver function tests normalized and erythrocyte sedimentation rate decreased to <20 mm in the first hour. A CT scan of the abdomen revealed significant decrease in the size of the periportal and peripancreatic lymph nodes. There was no evidence of biliary dilatation. The patient was doing clinically well after 6 months of antitubercular therapy.

PMC3890466_01

Female

A 74-yr-old woman was transferred to our hospital from a local clinic because of generalized weakness and high fever with chills on January 17, 2013. She had been complaining of abdominal discomfort. She had no underlying illness such as diabetes mellitus, hypertension, hepatitis, or tuberculosis. Her family history and social history were non-specific. For 15 days, prior to admission, she received conservative treatment for herpes zoster infection on the anterior chest without an anti-viral agent. At the time of admission, her body temperature was 37.8C and blood pressure was 110/80 mmHg. Her heart rate was 112 beats per minute being faster than normal with sinus rhythm on ECG. Laboratory examination revealed pyuria, isomorphic hematuria, positive leukoesterase and bacteria on urinalysis. Systemic leukocytosis with a predominance of neutrophils (white blood cell count of 21,650/microL) and a high C-reactive protein level of 35.63 mg/dL were shown in the blood test. Blood urea nitrogen and serum creatinine level had risen to 69.4 mg/dL and 4.28 mg/dL, respectively, from normal values at baseline. Serum potassium was 6.0 mM/L, and coagulation test results were lengthened to a PT INR of 1.4 and an aPTT time of 70.2 sec. Physical examination was otherwise unremarkable except diffuse abdominal tenderness. Through laboratory tests and physical examinations, the patient was suspicious of urinary tract infection combined with acute kidney injury. Next, a computed tomogram (CT) was checked and it revealed hydronephrosis with upper ureteral stones and multiple ill-defined hypodense lesions suggestive of acute pyelonephritis in both kidneys. Percutaneous nephrostomy (PCN) was performed in both kidneys, and during this procedure, right PDF was visualized. Pyelography revealed a fistula to the descending part of the duodenum (Fig. 1). We prescribed total parenteral nutrition and intravenous antibiotics and planned surgery for PDF. However she was too old and was considered to be emaciated to tolerate nephrectomy and general anesthesia. Also, the surgeon was not able to find out the exact leakage site on CT. Therefore, gastroendoscopy was decided to avoid surgery. The gastroenterologist discovered PDF in the duodenal second portion and clipped the lesion 4 times (Fig. 2). After an appropriate course of parenteral antibiotics therapy with the clipping procedure, her temperature and white blood cell count returned to normal, and her urine culture grew Klebsiella pneumoniae which showed all sense to the antibiotics. The patient, however, had to undergo one more endoscopic procedure after 1 week because her follow-up fistulography revealed that there was still a communication between the pelvis and duodenum, but the amount of leakage was significantly reduced. The gastroenterologist ligated the fistula site with a detachable snare which is an elliptically shaped nylon loop used to tighten around the fistula site. This device has recently been used for closure of gastrointestinal fistula followed by application of a clip in the field of gastroenterology. Follow-up fistulography was performed after 1 week, and we were able to confirm there was no more leakage (Fig. 1). Her blood urea nitrogen and serum creatinine levels recovered to normal showing 10.7 mg/dL and 0.86 mg/dL, respectively. Her urine culture was returned to negative finding. She was discharged after confirmation of appropriate oral intake on admission day 30. The urologist removed PCN in the outpatient clinic, and then finally treated her stones by extracorporeal shockwave lithotripsy.

duodenal diseases, endoscopy, intestinal fistula, kidney diseases, urinary fistula

PMC7728737_01

Male

A 9-week-old male (ex 34 weeks gestational age, corrected age 3 weeks) had been referred to our Emergency Department with suspected surgical abdomen. He presented a 3-day history of non-bilious, non-bloody vomiting and a 2-week-history of increasing abdominal distention and scrotal swelling. The patient was the second child of his parents who are from Kerala, India, and distantly related (3rd degree cousins). The couple's firstborn son is healthy. Pregnancy was complicated by moderate oligohydramnios and decreased fetal movements which led to urgent C-section. Mother denied fever or rash during pregnancy, and her urinalysis was normal. Birth weight was 1970 g (20th weight percentile). The weight of the placenta is not known. APGAR was 8 and 8 after 1 and 5 min, respectively. He received CPAP and then oxygen via nasal cannula for a total of 3 days. A post-natal brain ultrasound study was reportedly normal, TSH was 12 mU/L, and he was discharged home after 6 days. Immunizations were up-to-date, including PCV13. At presentation, the infant was alert, irritable, pale and grunting. He was normocephalic without dysmorphic features. There was no rash, no jaundice, no petechiae or ecchymoses. He was tachycardic at 175 beats per minute and tachypneic. The remainder of the cardiovascular and pulmonary findings was unremarkable. The abdomen was distended, tense and shiny with large ascites and no palpably enlarged liver or spleen. Substantial scrotal edema was noted. Weight (with edema) was 3.5 kg (0.01%, z score -3.83), length 52.5 cm (0.00%, z score -4.31), and head circumference 35.5 cm (0.04%, z score -3.35). At the time of admission, there was large proteinuria, hypoalbuminemia, and hypercholesterolemia, consistent with nephrotic syndrome. Nephrotic range proteinuria was defined as a spot urine protein-to-creatinine ratio of >0.23 g/mmol (corresponding to >2.0 g protein/g creatinine). For details and definitions, see Table 1). The hemoglobin (Hb) level dropped from 100 to 69 g/L over the first 10 days of admission, with inadequate reticulocyte response and normal serum ferritin and iron levels. Serum C3 and C4 concentrations, measured on day 11 of admission, were decreased. The concomitant direct agglutination (Coombs) test was negative. Secondary findings were hypogammaglobulinemia, hypothyroidism with elevated TSH and low free T4 levels, hypovitaminosis D, low-normal serum ionized calcium (1.17 mmol/L) and moderately elevated intact PTH. ALT and AST were normal. GGT and bilirubin concentrations peaked during the first few days after admission (see Table 1). The ultrasound (US) scan showed enlarged kindeys with mildly increased cortical echogenicity. Liver and spleen were of normal size and echotexture. The brain US study was normal, except the presence of thalamostriate mineralizing vasculopathy. Cardiac echography demonstrated a small perimembranous ventricular septal defect of 2-3 mm with left-to-right shunt and patent foramen ovale, none requiring specific interventions. Infectious disease workup revealed anti-CMV IgM antibodies and CMV DNA (by PCR) in blood and urine. Maternal screening during pregnancy for toxoplasma (IgG and IgM), rubella (IgM), HIV 1 & 2 antibodies/P24 antigen, hepatitis B (HBsAg) and hepatitis C (antibodies), and syphilis was negative. Subsequent CMV testing showed high maternal serum concentrations of CMV IgG, but no anti-CMV IgM. Treatment consisted of frequent albumin infusions, diuretics and ACE inhibition, with improvement of ascites and peripheral edema. He also received L-thyroxin, vitamin D and oral penicillin prophylaxis, low-dose acetyl salicylic acid, iron, and indomethacin. In addition, he was vaccinated against Streptococcus pneumoniae (PCV13, twice) and hepatitis B. Valganciclovir treatment was initiated 9 days after presentation at a dose of 22 mg/kg/day. CMV DNA became undetectable in plasma and urine after 1 month of antiviral therapy, however proteinuria failed to improve (Table 1) strengthening the presumptive clinical diagnosis of a genetic form of congenital nephrotic syndrome.

finnish-type nephrotic syndrome, nphs1, streptococcus pneumoniae, case report, cytomegalovirus, glomerulonephritis, infantile nephrotic syndrome

PMC7154259_01

Male

A 41-year-old male presented at his local eye clinic with the primary complaint of decreased visual acuity (VA) in his left eye. Upon examination, a subretinal tumor mass was observed in his left eye, and he was subsequently referred to the Department of Ophthalmology, Osaka Medical College, Takatsuki, Osaka, Japan for more detailed examination and treatment. His medical and family history was unremarkable. His VA was RV = (1.2 x S-7.5D) and LV = (0.04 x S-8.0D), and his intraocular pressure was 17 mm Hg in both eyes. No abnormalities were noted in the right eye, but a few inflammatory cells were observed in the vitreous and anterior chamber of the left eye. Fundus examination showed no particular abnormalities in the right eye (Fig. 1a), but a large white protruding lesion of 10 papilla diameter (PD) (lateral diameter) x8 PD (longitudinal diameter) in the macular region, and slightly temporal to it, in the left eye (Fig. 1b). B-scan ultrasonography (UD-8000; Tomey Corp., Nagoya, Japan) was performed and revealed that the lesion in the left eye appeared to have high internal reflectivity (Fig. 2). Examination by optical coherence tomography (OCT) (SPECTRALIS ; Heidelberg Engineering GmbH, Heidelberg, Germany) revealed no abnormalities in the right eye. In the left eye, a protruding lesion was observed with a homogenous shadow on the choroid and under the retina, which was complicated by exudative retinal detachment around it (Fig. 3a, b). Fluorescein angiography (TRC-50DX Type IA; Topcon Corp., Tokyo, Japan) showed slight fluorescein leakage in the peripheral region of the right eye (Fig. 4a). In the left eye, punctate fluorescein leakage corresponding to the tumor-like mass was noted at the early phase (Fig. 4b, c), and tissue staining and fluorescein pooling were observed from the middle to late phase (Fig. 4d, e). Indocyanine green angiography (TRC-50DX Type IA) revealed low fluorescence and filling delay in the area corresponding to the tumor mass (Fig. 5a, b). Whole-body contrast-enhanced computed tomography (CT) was performed, since the choroidal tumor was also suspected on the basis of the above findings. The CT results showed that there were enlarged lymph nodes throughout the body, including both sides of the neck, the supraclavicular fossa, both sides of the mediastinum, and the pulmonary hilum. Thus, the patient was subsequently referred to the Department of Respiratory Medicine at Osaka Medical College Hospital, and since sarcoidosis was suspected, a biopsy of the right cervical lymph nodes was performed at the Department of Plastic Surgery. The results showed a noncaseating epithelioid cell granuloma. Blood test results were as follows: the angiotensin-converting enzyme finding was 15.2 U/L (reference range 8.3-21.4 U/L), the soluble interleukin-2 receptor finding was 987 U/mL (reference range 145-519 U/mL), the toxoplasma IgM and IgG test findings were within the normal reference range, and the enzyme-linked immune absorbent spot assay finding (tuberculosis) was negative. Choroidal granuloma due to sarcoidosis was diagnosed on the basis of both the pathological examination results and the ophthalmologic findings. Steroid pulse therapy (methylprednisolone 1,000 mg for 3 days) was performed due to a rather large lesion compared with that of past reports. After one cycle of steroid pulse therapy, the prednisolone was tapered to 60 mg/day. Triamcinolone was once injected into the sub-Tenon capsule, but it was withdrawn due to an increase in intraocular pressure. After the initiation of steroid therapy, the choroidal granuloma gradually decreased in size, and the patient's VA gradually improved at 3 weeks and beyond after the start of treatment (Fig. 5a, b). At 2 months after the start of treatment, the choroidal granuloma was markedly decreased, the exudative retinal detachment had disappeared, and the patient's corrected VA had improved to 0.7 (Fig. 6a, b). At 1 year after the start of treatment, the choroidal granuloma had further decreased, although atrophy of the retinal pigment epithelium was detected, and the patient's corrected VA was maintained at 0.8. There was no increase in intraocular pressure during the 1-year period of steroid pulse therapy.

choroidal granuloma, sarcoidosis, steroid pulse therapy

PMC10361055_02

Female

Patient B was a 72-year-old woman diagnosed with severe Alzheimer's disease. She had lived in the institution since September 2019. She needed assistance and close monitoring in performing daily activities, for example changing clothes, and communication. Kabochan was selected for her as she could do only limited interaction while sitting. For one of the cases, data were collected at an institution for older persons and another from a psychiatric hospital in a prefecture in western Japan. The institution for older persons provided daily and long-term nursing care services, particularly ensuring personal hygiene maintenance such as bathing, exercise, meals, and activities of daily living. The healthcare staff provided daily healthcare activities that started in the morning and continued until evening. The other institution is a private hospital for patients with mental health problems such as dementia and schizophrenia. In these settings, both the Pepper and Kabochan were regularly used for physical exercises and recreational activities. Patient A and Patient B were patients in one of these settings and were familiar with the healthcare robots. They were able and willing to participate and familiar with the two robots, Pepper and Kabochan. Data were collected in November 2019. Digital video recordings were made during similar interactions in two separate transactive care situations. Research assistants were trained to observe and note the interactions among the older persons, Pepper and Kabochan, and the intermediary. During the data collection period, the researchers recorded field notes regarding significant situational events between the older person, Pepper, Kabochan, and the nurse intermediary. The field notes also included researcher reflections during the interactions. Observation notes and recorded dialogues were transcribed and translated into English. Those data supported with recorded scenes (pictures) were analyzed and interpreted carefully by reading and rereading the transcriptions and carefully watching and listening to audiovisual recordings. The significant data were highlighted and grouped into the same identified thematic categories. (Please see Figure 3 for the examples of data used for analysis). The first situation was between Patient A and Pepper. Pepper is a humanoid robot manufactured by SoftBank Robotics, with applications made by Xing Company, Japan (Tanioka et al.,). This clinical examination utilized the "Kenko Okoku" Talk application for Pepper to enhance human-robot interaction through improved communication between older people and humanoid robots (Miyagawa et al.,). This Pepper has been used for communication purposes and could identify humans and respond to conversations. The second situation was among Patient B, Kabochan with Pechat, and the nurse as an intermediary. The intermediary facilitated the conversation between Patient B and Kabochan by repeating and supporting the question and answer for Patient B when she indicated that she did not hear the words uttered by Kabochan. Data were generated from two nursing care activities involving conversations and observations recorded through sophisticated audio-video technologies. These observations recorded interactions among older persons with mental health conditions, healthcare robots (Pepper and Kabochan), and a nurse as an intermediary. Osaka has described the role of an intermediary as a nurse or healthcare provider who is "the critical component of a responsive management program" (p. 267). A qualitative thematic analysis following Lambert and Lambert was used to analyze and interpret the data. Lambert and Lambert described a process of thematic analysis as an approach in qualitative descriptive study, in which interviews, written descriptions, or observational recordings are used as data. In the qualitative descriptive analysis, a window to the experiential occasion is not moderated by adhering to established criteria such as saturation point and the number of patients, but by the philosophical underpinnings appreciated as the guiding principles for robust analysis and interpretation of data. In essence, a descriptive statement ultimately answers the research question describing the phenomenon being studied (Sandelowski,). The framework for the analysis and interpretation was grounded from TRETON (Tanioka,). TRETON clarifies the shared engagement that occurs in nursing situations involving healthcare robots as partners. Generated data using observational and conversational dialogue during a transactive relational engagement between healthcare robots, older persons with mental health conditions, and the nurse as intermediary were analyzed and interpreted. Interpretation of the data emphasized the dialogical engagement context, as described and explained by Vaismoradi et al.. The presentation of the findings was done through a straightforward descriptive statement in which the organization of the results greatly depended on the researchers' understanding of the descriptions and how the data were extracted (Lambert & Lambert,). Trustworthiness and rigor were established through triangulation and detailed transcription (Gunawan,). Triangulation was conducted by generating data from multiple sources, including digital-video recordings, photographs, conversational dialogue, observation, and reflections field notes, which were also transcribed. Detailed descriptions of the patients, the settings, and the data collection process were presented. Audit trails were done by the researchers supporting the derived themes. Additionally, findings, discussions, and conclusions were confirmed to fit the data gathered. The research team consisted of five experienced scholars and researchers with two doctoral students as co-researchers. No conflicting relationships between the research team members and with patients were found to influence the findings. The study was approved by the Ethics Committee of the Tokushima University Hospital (# 3046) and the Mifune Hospital Clinical Research Ethics Review Committee (#201180502). Patients and their responsible family members approved their participation, including being audiotaped and having excerpts from transcripts and altered photos from the audio-video recordings used in the research reports. Photographs taken during the data generation were blurred to protect identities.

japan, dementia, mental health, nursing, robotics, schizophrenia, technology

PMC9845030_01

Male

A 4-year-oldinfant boy with a history of soft tissue tuberculosis was treated at the age of one year. In November 2021, he was admitted to a university hospital with acute jaundice, fever, and vomiting. He was diagnosed with acute liver failure as a result of an infection with hepatitis A virus. The anti-HAV antibody immunoglobulin M (IgM) was elevated, and antibody immunoglobulin G (IgG) was negative. It was detected by using an enzyme-linked immunosorbent assay (ELISA). It was confirmed by the detection of HAV by real-time PCR. Serological tests for hepatitis B virus (HBV), hepatitis C virus (HCV), human immunodeficiency virus (HIV), cytomegalovirus (CMV), toxoplasmosis, rubella, and EBV were all negative. The infant still had a high fever, asthenia, and myalgia a week later. The patient had a painful case of hepatomegaly and splenomegaly. Following a thorough examination, the patient was diagnosed with sepsis. Despite supportive antibiotic treatment, he deteriorated with persistent fever and irritability. The liver was palpable at 10 cm with a hepatic arrow, but the rate was not. In addition to a macular rash and edema in the lower and upper extremities, the following laboratory results were obtained: hemoglobin 5.5 g/dL, mean corpuscular volume (MCV) 81.2 fL, white blood cell count (WBC) 0.62 103/muL, and platelet count 97 103/muL. Transaminase levels were found to be elevated in the initial laboratory examination (Table 1). Urine cultures came back negative. However, the blood culture revealed the presence of two bacteria: Leuconostoc citreum and Brevibacterium ravenspurgense; he was treated with antibiotics, but the fever and asthenia persisted. An aspiration of bone marrow revealed the presence of histiocytes and lymphocytes at the medullary level. For three days, he received steroids via IV at a dose of 1 g/1.73 m2 and additional steroids via OS. On the third day of treatment, the patient's fever returned to normal, and his overall condition improved. On the fifth day of treatment, his ferritin level was reduced to 760 ng/L and his WBC level increased to 14400/mm3. His overall health had improved. The patient was discharged ten days later with no complaints. At the fourth month of follow-up, he was in good health.

PMC3895317_01

Male

The patient 21-year-old male presented 1 year back with fever for over 1 month, after detailed investigations including cerebrospinal fluid (CSF) examinations, he was diagnosed as a case of tubercular meningitis and was under remission and surveillance on anti-tuberculosis treatment-4 (ATT-4) (HRZE: Isoniazid, rifampicin, pyrazinamide, ethambutol) for 2 months, followed by ATT-2 (HR) regularly for 9 months, when he reported a swelling over his left supraclavicular region, on fine needle aspiration cytology (FNAC) this enlarged left supraclavicular lymph node showed tubercular abscess. Development of abscess despite being on regular ATT for 11 months was considered as multidrug resistance tuberculosis (MDR-TB); and hence, started on second line ATT, that is, cycloserine 500, ethionamide 500, ofloxacin 800 in two divided doses and streptomycin 750 mg per day along with continuation of ATT-2. After taking these medications for 7-8 days, he developed symptoms of excessive talkativeness, decreased need for sleep, irritable-aggressive behavior, overactivity, overfamilarity, and inflated self-esteem; and referred for psychiatric consultation. There was no past or family history of any significant psychiatric or medical illness; his general physical examinations were confirmatory of left supraclavicular lymph node enlargement. On mental status examinations, he had increased psychomotor activity, pressured speech, elated affect, and delusion of grandiosity. Young Mania Rating Scale (YMRS) score was 38, and Brief Psychosis Rating Score (BPRS) score was 51. Cycloserine was considered as most possible offending agent and discontinued, whereas other drugs were continued under close observation as inpatient facility. He received tab. divalproex 500 mg and olanzapine 5 mg per day initially, then his divalproex was increased to 750 mg/day. After 3 days, his YMRS score was 15 and BPRS was 33 and on 10th day there was no sign of manic symptoms. A score of 5 on Naranjo algorithm (Naranjo et al., 1981) suggests probability of cycloserine causing mania. We gradually tapered off olanzapine first then divalproex within a month, and there is no further affective symptoms reported or found on follow-ups. We have taken written informed consent for publication of this case report.

cycloserine, mania, psychosis

PMC4847832_02

Male

A 20 year old man presented with increasing lethargy and shortness of breath over the past 6 months after visiting parts of Africa. Recently he has lost weight, developed a fever and headache. His chest x-ray and CT scan of chest are as follows: Under normal circumstances clinical observations such as these would lead the diligent physician to conduct a full clinical assessment and seek to rapidly reverse the cause. At the time of this picture the individual concerned was comfortable, at rest and far from being in extremis. On the morning of May 23, 2007, after having spent 60 days at an elevation higher than 2500m, and having just summited Mount Everest (8848m), four climbers on the Caudwell Xtreme Everest Expedition had arterial blood sampling on their descent. The mean values for the climbers of PaO2 and PaCO2 were respectively 24.6mmHg/3.28kPa (Normal ref. 75-100mmHg/10-13.3kPa) and 13.3mmHg/1.77kPa (Normal ref. 35-45mmHg/4.67-6.0kPa); the lowest ever documented in humans. These measurements provide a picture of the pattern of and limits to changes in human blood gases in response to hypobaric hypoxia on the earth's highest mountain. In conjunction with initiating factors and the presence of coexisting conditions, hypoxia triggers numerous adaptive and maladaptive systemic responses that remain poorly understood. The authors suggested that an understanding of the limits of adaptation to hypoxia would be relevant to physicians who care for critically ill patients since many of the interventions aimed at restoring or maintaining cellular oxygenation often prove ineffective and may at times be detrimental. Panel C. Blood pressure is within 'normal' limits, and the pressure overnight is around 15% lower than that during the day (normal nocturnal dipping). In Panel B, there is no clear diurnal variation in blood pressure meaning that there is absent noctural dipping. Non-dipping can have innocent or pathologic explanations. Perhaps the patient works night shifts, and is asleep during the day, or perhaps the inflation/deflation of the sphygmomanometer cuff caused discomfort and resulted in a very poor night's sleep. Non-dipping has been also associated with obstructive sleep apnoea, diabetes mellitus, obesity, renal failure and other secondary causes of hypertension. In Panel A, the blood pressure is higher overnight than during the day - the so-called 'reverse dipping' pattern, which is again abnormal and in need of investigation. Panel D shows excessive dipping which has been linked with worsening of cardiovascular risk, perhaps due to under-perfusion of vital organs. Miliary Tuberculosis. The chest x-ray appearances of multiple pulmonary nodules (1-3 mm) is so called due to its similar appearance to 'millet seed'. Infection (e.g. TB, fungal), metastases (e.g. thyroid, renal, breast, melanoma, pancreatic), and sarcoidosis. NICE suggests 2 months of treatment with Isoniazid, Rifampicin, Pyrazinamide and Ethambutol, followed by 4 months with Isoniazid and Rifampicin. Extra-pulmonary sites of infection commonly observed in TB include: lymph nodes, pleura, osteoarticular, skin and liver, although any organs can be involved. There are various central nervous system manifestations, one of which is tuberculomas which could explain this patient's headache. Tuberculosis (TB), caused by Mycobacterium tuberculosis, remains a significant global disease, with protean manifestations, albeit a disease most commonly associated with the respiratory system. One of the more uncommon forms of pulmonary TB is miliary TB, in which tiny deposits form innumerable nodules between 1-3 mms in the lungs. These are typically uniform in size and diffusely distributed in both lungs. This form of the disease often presents in the sickest patients and represents haematogeneous dissemination for which the prognosis is poor. The name miliary arises from the similarity of the appearances in the lungs to that of millet seed. Millet seed is grown for use in feed for the animal industry as well as a health food for humans. TB is a truly multi-system disease and can manifest in any organ system, including various central nervous system manifestations, one of which is tuberculomas. Cold abscesses of the neck and chest wall are also a recognised presentation.

PMC5865275_01

Female

A 14-year-old girl presented with 5-day history of continuous high-grade pyrexia on a background of a year's history of mild intermittent polyarticular arthralgia. The joints involved were the wrists, fingers, elbows, knees, ankles, and toes. There was no associated swelling, redness, or deformity. The joint pains were not associated with early morning stiffness. Her immunizations were up-to-date including BCG. She is the only child of Irish parents. Review of system revealed nondistressing chronic cough, anorexia, and occasional night sweats. History of TB contact was unknown. She had occasional malar rash which was thought to be flushing of cheeks. Examination findings revealed a febrile girl in mild respiratory distress. She appeared pale, no digital clubbing or peripheral lymphadenopathy. Her vital signs were as follows: temperature 38.50 C, pulse rate 115 beats/minute, respiratory rate 32/minute, blood pressure 100/58 mmHg, and oxygen saturation 88% in room air. There was decreased chest expansion on the right. Air entry was diminished on the right upper and mid zones but absent at the base. Stony dull percussion on the right hemithorax was elicited. Full blood count showed haemoglobin level 11 g/dL, white cell count 4000/mm3 (neutrophils 60%, lymphocytes 31%, and monocytes 9%), and platelet count 243,000/mm3. MCV was 71.7 fL, and MCH was 24 pg. Erythrocyte sedimentation rate (ESR) was 83 mm/hour, and C-reactive protein (CRP) was 54.8 mg/L. Lactate dehydrogenase (LDH) was 465 U/L, and urate was 401 micromol/L. The renal function and liver function tests were normal. Autoimmune screening showed that anti-nuclear antibody (ANA) was strong positive homogenous and anti-double-stranded DNA was >379 IU/ml. Other positive antibodies include extractable nuclear antibody, crithidia anti-double-stranded antibody, and anti-Ro and anti-La antibodies. IgM rheumatoid factor was <11.4 IU/mL. Serum ACE level was 47 U/L, and low C3 and C4 levels were at 0.73 and <0.08 g/L, respectively. Quantiferon TB1 and TB2 were 2.34 and 1.75 IU/ml, respectively. Pleural fluid biochemical analysis showed pH 7.25, protein 50 g/L, glucose 64 mg/dL, and LDH 256 U/L. There was pleural fluid lymphocytosis (85%) with no culture growth. Pleural fluid cytology showed loose aggregates of histiocytes and poorly formed granuloma (Figure 1). Bronchial lavage sample yielded no growth on culture. Chest radiography (Figure 2) demonstrated moderate to large volume right-sided pleural effusion. Contrast-enhanced computed tomography (CT) scan of thorax showed large right pleural effusion, bilateral axillary lymphadenopathy, and a bulky left hilum (Figure 3). The Mantoux test (before immunosuppressant therapy) was negative. She was initially treated as a case of parapneumonic effusion. She received a 4-day course of antibiotics. Ultrasound-guided pigtail drain was inserted on her right chest, which drained approximately 2000 ml of serosanguinous fluid over 24 hours. Rheumatology team in view of SLE commenced her on a 3-day course of intravenous methylprednisolone and a 10-day course of tazobactam/piperacillin. She was continued on high-dose oral prednisolone. Other medications include hydroxychloroquine 200 mg once daily, mycotil mycophenolate (CellCept) 250 mg 12 hourly, and omeprazole 20 mg once daily. Following review of investigations by infectious disease team, she was started on quadruple anti-TB treatment (isoniazid, rifampicin, pyrazinamide, and ethambutol) and pyridoxine. There was gradual but steady clinical improvement while on the SLE and TB treatments. Chest radiograph at 15 weeks of treatment showed near-complete resolution of effusion. She was on regular follow-up with the dietician, occupational therapist, and physiotherapist. Her inflammatory markers have returned to normal limits. She is currently enjoying school having been on treatment for 5 months.

PMC8269762_02

Female

Two additional cases of transient abducens nerve palsy in two young otherwise healthy patients were noted in May 2020. Both patients reported clinically suspicious symptoms of COVID-19 in the weeks preceding the development of the nerve palsy. Unfortunately, neither individual met government testing criteria at the time of onset so real-time reverse transcription polymerase chain reaction (RT-PCR) tests were not performed, therefore COVID-19 diagnosis was unconfirmed. Similarly, antibody testing was unavailable for the general public at this time. Moreover, anosmia was not listed as an official symptom of COVID-19 by the UK government until 19th May 2020. Since May 2020, understanding of COVID-19 presentation has developed; consequently, more symptoms are formally recognised. Patient A was a healthy 47-year-old Caucasian female schoolteacher who presented with isolated left abducens palsy. She reported symptoms of sore throat, fatigue, shortness of breath, headache, dizziness and nausea seven weeks prior to the diplopia onset. Diplopia fully resolved in primary position within one month. Residual esophoria was present on laevoversion and dextroversion. Patient B was a healthy 38-year-old male of Chinese ethnicity who presented with isolated right abducens palsy. He worked as a caregiver in a residential home setting with recent confirmed COVID-19 outbreak. He reported symptoms of dry cough, sore throat and malaise two to four weeks prior to onset of diplopia. Diplopia in primary position resolved within one month. Ocular motility was full. In both cases, ophthalmological assessment was unremarkable and MRI scans normal. In the absence of a space occupying lesion and demyelination, post-viral aetiology was suggested. Both patients worked in high-risk occupations, hence COVID-19 exposure is highly possible. Notwithstanding, this evidence is speculative in the absence of a confirmed positive COVID-19 test.

covid-19, abducens palsy, anosmia, diplopia, neurological

PMC2262903_01

Male

A 17-year-old male with progressive visual loss and photopsia was admitted to our ophthalmology clinic. He had a history of blunt trauma with a basketball to his right eye 6 months ago and had begun to suffer from visual disturbances since then. His visual acuity (VA) was 20/400 in his right eye. Dilated fundus exam of his right eye revealed a giant tear in the superotemporal retina with a shallow retinal detachment involving the macula (Figure 1a and 1b). His visual acuity was 20/20 and anterior and posterior segments were normal in the left eye. He underwent a three-port pars plana vitrectomy for the giant tear without crystalline lens extraction. Perfluorodecaline was used intraoperatively. Three weeks postoperatively, perfluorodecaline was observed in the anterior chamber in contact with the corneal endothelium (Figure 2). No tilt or dislocation of the crystalline lens was detected on slit lamp biomicroscopy. We referred our patient to another eye clinic for ultrasound biomicroscopic (UBM) or endoscopic examination in order to determine zonular dialysis, but could not obtain these results as the patient refused (4) After our attempt to remove the perfluorodecaline in the anterior chamber with a 27G needle failed, an anterior chamber wash was performed with balanced salt solution via two wide paracentesis. Two months after vitreoretinal surgery, his best-corrected visual acuity (BCVA) was 40/200 in the right eye. The vision and retina remained stable in his follow-up (Figure 1c).

PMC5376921_01

Female

A forty-five-year-old female reported to the Department of Conservative Dentistry and Endodontics, with the chief complaint of pain in #14 and #15 and extra oral swelling on the right side infraorbital region (Figure 1). History revealed that the swelling was present for more than a year. It was asymptomatic and slow growing in nature. Patient had experienced occasional hypersensitivity with food impaction in #14 and #15 for the past few months. But a severe pain of sudden onset led her to seek dental assistance. General physical examination revealed that patient was normally built for her age. There was no defect in stature or gait. Her medical and family histories were noncontributory. Extraoral examination revealed a diffuse swelling extending from the inferior border of orbit to the level of occlusal plane. The overlying skin was normal in colour. On palpation, swelling was soft and compressible in nature. Intraoral examination revealed carious involvement in 14 and 15 with both teeth exhibiting tenderness to percussion. There was no obliteration of the buccal vestibule in spite of the presence of extraoral swelling (Figure 2). Intraoral periapical radiographs (Figure 3) revealed coronal radiolucency extending into the pulp accompanied by widening of the periodontal ligament space in both #14 and #15. Orthopantomographs (Figure 4) were advised to investigate the radiographic changes in relation to the extraoral swelling, but in vain. Both #14 and #15 responded positively to electric and cold pulp testing. Consequently, it was concluded that the swelling may not be of dental origin. Complete blood and urine investigations were performed which ruled out systemic conditions like diabetes mellitus, HIV, HSs, tuberculosis, or leukemic enlargement. Thereby any possibility of an infectious enlargement was dismissed. The patient was referred to Department of General Medicine for opinion regarding the extraoral swelling. CT scans were taken which revealed an irregular soft tissue mass measuring 18 x 16 mm in the subcutaneous plane of the posterior maxillary region (Figures 5(a) and 5(b)) on the right side. The lesion appeared separate from the maxillary antrum and there was no bony expansion. Duplex ultrasonography confirmed the presence of a single feeding vessel into the lesion and the lesion was diagnosed as haemangioma. Patient was referred to the vascular surgeon who was further briefed about the need for endodontic therapy. Patient was advised sclerotherapy under Duplex ultrasonographic guidance. 1 mL of foam 3% polidocanol was injected intralesionally and compression bandage was applied. A one-month follow-up CT showed a significant reduction in the size of the lesion (18 x 12 mm) and consent was given to proceed with endodontic treatment. Local anaesthetic (Lignox 2%A) was administered via infiltration. Access opening was done in #14 and #15, under rubber dam isolation. Working length determination was done using an electronic apex locator (J Morita, USA, Inc.) and later confirmed radiographically to circumvent the risk of overinstrumentation. Canals were irrigated with 3% sodium hypochlorite. Root canals were cleaned and shaped with Protaper files (Dentsply-maillefer, Ballaigues) up to size F2 and obturated in a single visit (Figure 6(a)). Patient was reviewed after 1 week during which she was asymptomatic and postendodontic restoration was done with light cure composite resin (3M ESPE, USA). Patient continued to remain asymptomatic during follow-ups done at 3 and 6 months (Figure 6(b)) and was under her regular sclerotherapy sessions. Informed written consent was obtained from the patient with regards to the publication of her extraoral, intraoral, and radiographic images.

PMC7406069_01

Female

An 8-year-old girl with TM received granulocyte colony stimulating factor mobilized peripheral blood stem cells (PBSCs) from an unrelated human leukocyte antigen (HLA) 9/10 matched donor. The myeloablative conditioning regimen consisted of cyclophosphamide (CTX), busulfan (BU), fludarabine (FLU), and rabbit anti-thymocyte globulin (ATG). Graft-versus-host disease (GVHD) prophylaxis included cyclosporine (CSA), low dose methotrexate (MTX), and mycophenolate (MMF). Neutrophil engraftment was achieved by day 14 post-transplantation. The donor cell chimerism was >99%. Patient A was discharged on day 25 post-transplantation without severe complications. The patient was readmitted for persistent high fever and cough on day 73 post-transplantation. Chest computed tomography (CT) scans suggested mild pneumonia without severe pulmonary lesions (Figure 1A). Despite the administration of broad-spectrum antibiotics and antifungal treatments, the patient developed severe respiratory distress requiring ventilatory support starting on day 82 post-transplantation. A bronchoscopy was performed at this time. Bronchoalveolar lavage (BAL) fluid tested positive for Mtb DNA (2.79 x 103 copies/mL), cytomegalovirus (CMV) DNA (2.65 x 105 copies/mL), and Epstein-Barr virus (EBV) DNA (8.68 x 104 copies/mL) by real-time PCR analysis. Acid-fast bacilli (AFB) testing of the BAL fluid was negative. Thus, diagnoses of pulmonary TB, CMV, and EBV were considered. Ten days after the patient was hospitalized, TB treatment consisting of isoniazid, rifampin, and pyrazinamide, and antiviral therapy consisting of ganciclovir and intravenous immunoglobulin (IVIG) were initiated. The patient was removed from ventilator support 90 days post-transplantation. Four days after the removal of the ventilator, the patient developed hematemesis and hemoptysis with continued high fever and persistent cough. A chest CT scan revealed the progression of pneumonia with massive pulmonary infiltrates (Figure 1B). The patient was again placed on a ventilator, and pneumorrhagia was observed during intubation. Streptomycin, linezolid, and levofloxacin were immediately added to the patient's treatment regime and antiviral treatment was changed to ganciclovir and foscarnet sodium. Empiric antibiotic and antifungal treatments were ongoing. The patient developed signs of hemophagocytic lymphohistiocytosis syndrome, including significant enlargement of the liver and spleen, pancytopenia, sudden elevated serum ferritin (18298 mmol/L), and delayed coagulation time. Methylprednisolone was added to the patient's treatment regime. The patient was removed from the ventilator support after showing progress. On day 110 post-transplantation, the patient was discharged and continued on a modified TB treatment regime of oral isoniazid, rifampin, and pyrazinamide. Chest CT scans performed on day 326 post-transplantation revealed almost full resolution of pulmonary infiltrates (Figure 1C). The patient was continued on oral isoniazid, rifampin, and pyrazinamide treatment for a year before the discontinuation of anti-TB treatment.

hematopoietic stem cell transplantation, pediatric, thalassemia, tuberculosis

PMC7406069_02

Male

A 9-year-old boy received a haploidentical bone marrow (BM) and GCSF mobilized PBSC transplant from his biological father for TM treatment, and an HLA-mismatched umbilical cord blood (UCB) transplant from an unrelated donor 6 days later. The patient's preparation regime consisted of CTX, BU, FLU, ATG, and thiotepa (TT). GVHD prophylaxis included post-transplant CTX, MMF, and tacrolimus (FK506). Neutrophil engraftment, delayed owing to UCB engraftment, was observed by day 40 post-transplantation with an absolute neutrophil count greater than 0.5 x 109 cells/L. On day 79 post-transplantation, the patient was treated for CMV reactivation with IVIG. Critical complications, including severe GVHDs, refractory pancytopenia, and life-threatening infections were not observed. Patient B returned to the hospital with intermittent fever and enlargement of the lymph nodes of the neck and groin on day 89 post-transplantation. An ultrasound revealed that largest lymph node in the neck was 2.6 cm x 1.0 cm. Chest CT scans showed enlarged mediastinal and bronchial lymph nodes without significant pulmonary lesions (Figure 1D). PCR revealed plasma EBV-DNA (1.08 x 105 copies/mL). Post-transplant lymphoproliferative disorder (PTLD) was suspected but could not be confirmed owing to the refusal of the patient's parents to provide consent for a lymph node biopsy. A positron emission tomography-CT (PET-CT) scan revealed enlarged lymph nodes with increased uptake of fluorodeoxyglucose in the neck, mediastinum, abdomen, and groin, supporting a diagnosis of PTLD. Consequently, the patient was administered foscarnet sodium, and rituximab once weekly for 3 weeks, a course of CTX, and a donor-derived EBV-specific cytotoxic T lymphocyte infusion between day 89 and 114 post-transplantation. The patient also received broad-spectrum antibiotics and prophylactic antifungals. The patient tested negative for EBV-DNA after receiving the first dose of rituximab. Two weeks after the onset of symptoms, the patient had accelerated chest pain and breathing difficulties. On day 114 post-transplantation, biopsies of the lymph nodes in the neck were performed showing granulomas with caseous necrosis, indicating lymph node TB. On day 116 post-transplantation, AFB testing confirmed TB, and treatment with isoniazid, rifampin, pyrazinamide, levofloxacin, and linezolid was started immediately. The patient did not improve and developed severe chest pain, tachypnea, hypoxemia, and orthopnea within 5 days of the initiation of anti-TB treatment. Chest CT scans revealed bronchial stenosis in both bronchial tubes and worsening lymphadenectasis. A bronchoscopy revealed multiple granulomas severely restricting the primary bronchi (Figure 1G, H). AFB testing was negative; however, BAL fluid tested positive for Mtb by PCR. Patient B developed type 1 respiratory failure after a week. Chest CT scans revealed massive infiltration, consolidation, and atelectasis of the right upper lobe of the lung, suggesting pulmonary TB (Figure 1E). The patient was then put on a ventilator after 3 days. Cryosurgery was performed via bronchoscopy to remove the granulomas and open the airways (Figure 1I). After a second cryosurgery, the patient showed gradual improvement. On day 155 post-transplantation, a bronchoscopy showed clearance of granulomas from the bronchi (Figure 1J). On day 166 post-transplantation, chest CT scans revealed the dissolution of the majority of pulmonary infiltrates, and the patient was discharged (Figure 1F). He was prescribed oral rifapentine, isoniazid, pyrazinamide, and linezolid for a week, and then changed to rifapentine, isoniazid, and pyrazinamide treatment for the following 4 weeks. Pyrazinamide was discontinued after a month owing to elevated liver enzyme levels and as of the writing of this case report, the patient continues to receive oral rifapentine and isoniazid.

hematopoietic stem cell transplantation, pediatric, thalassemia, tuberculosis

PMC4778191_01

Male

A previously healthy, 4-year-old boy, a resident of Uttar Pradesh presented with a history of a generalized headache for 1 month, intermittent high-grade fever associated with vomiting for 1 week. This was accompanied by 7-8 episodes of generalized tonic-clonic seizures lasting for 3-5 min for 1 day. The child had a history of geophagia and would often play in the garden with compost soil. There was no history of swimming or contact with tuberculosis. The patient was Human immunodeficiency virus (HIV) seronegative. On admission to our hospital, the child was restless and febrile and was in a tonic posture. CNS examination showed marked neck stiffness; brudzinski's and kernig's sign were positive with no focal neurological deficit. Cerebrospinal fluid (CSF) examination revealed: Proteins 16 mg%, sugar 40 mg% with 20 cells/mm3 (predominantly lymphocytes). The wet mount of CSF showed the presence of organisms morphologically resembling trophozoites of Acanthamoeba species. Giemsa stained smear confirmed the presence of amoeba. CSF microscopy and cultures were negative for bacteria and fungi. CSF was inoculated onto nonnutrient agar plates covered with a lawn of Escherichia coli and incubated at 37 C. After 24 h of incubation, many cysts consistent with Acanthamoeba species were observed [Figure 1]. A diagnosis of amoebic meningoencephalitis was made. Computed tomography (CT) scan report showed mild hydrocephalus. Blood and stool culture for bacteria and fungi were also negative. The patient was treated with mannitol, dexamethasone, and phenytoin. Amphotericin-B, rifampicin, and trimethoprim-sulfamethoxazole were subsequently initiated and continued for 21 days in appropriate doses. Nursing care, nutrition was maintained, and antipyretics were given four hourly. Treatment was continued, and thereafter patient's condition improved and discharged from the hospital. The patient came back again after 1.5 months with similar complaints. With the help of clinical picture, CSF cytology, CSF wet mount examination a diagnosis of Acanthamoeba meningoenencephalitis was made. The patient was treated with Mannitol, Phenytoin, and a combination of Amphotericin-B, Rifampicin, and Trimethoprim-sulfamethoxazole in appropriate doses, the response to treatment was not favorable and patient succumbed to his illness. During a 11/2 year period, we witnessed 6 more cases of amoebic encephalitis diagnosed on direct microscopy and subsequently isolated on culture [Table 1]. However, in one case Acanthamoeba could not be isolated in culture and, in this case, diagnosis was confirmed on the basis of direct microscopy findings. Blood cultures and CSF culture for bacteria and fungi were negative in all cases. No acid fast bacilli were seen on Ziehl Neelsen staining of CSF smears, and peripheral blood smear examination revealed the absence of malarial parasites. Acanthamoeba is free-living amoebae widely distributed in the environment. The routes of entry include a break in the skin or by inhalation of windblown cyst leading to amoebae invasion of the CNS through hematogenous spread. The involvement of the CNS can result in fatal consequences within days or weeks. Occasional survivors of disease have also been reported. In our series of cases, all were in the pediatric age group and had a rural background with close proximity to soil. These patients might have acquired the infection through inhalation of cyst. In three of our cases, presentation was acute, and rest of the cases had a sub-acute or chronic presentation. The acute presentation could be due to the accompanying risk factors [Table 1] as reported previously in a recent case. The clinical picture of GAE may resemble viral, bacterial or tuberculosis meningitis. Three of our cases were empirically started on anti-tubercular (TB) therapy suspecting of TB meningitis as it being a common diagnosis in developing countries. The majority of GAE cases due to Acanthamoeba are limited to individuals with a weakened immune system; particularly at risk are individuals with fungal and mycobacterial infections, patients on immunosuppressive therapy, HIV seropositive patients, etc. According to some recent reports, Acanthamoeba infection was also seen in immunocompetent persons. All our cases were HIV seronegative, one patient was undergoing immunosuppressive therapy for malignancy, and another patient had TB meningitis with communicating hydrocephalus as a risk factor. Rests of the patients were immunocompetent with no accompanying illness. The symptoms of GAE are similar to other CNS pathogens which makes GAE diagnosis problematic. The CT or magnetic resonance imaging scan may prove inconclusive. The CSF findings, although not confirmatory of GAE, are of value in diagnosing the CNS involvement. Pleocytosis with lymphocytic predominance is an important feature as observed in all of our cases. The confirmatory evidence comes from direct microscopic observation of amoebae in the CSF and amoeba culture. Acanthamoeba can also be grown axenically, and for rapid diagnosis molecular methods have been developed. Delayed diagnosis and limited efficacy of anti-amoebic agents to cross the blood-brain barrier often lead to failure in treatment. Current therapeutic agents have been tried in various combinations, but none of the regimes have been proved to be particularly effective, especially in immunocompromised patients. In our series of cases, two children presenting with amoebic encephalitis with accompanying risk factors and one case presenting with recurrence of amoebic encephalitis succumbed to their illness. Rest of the cases responded clinically with a combination of amphotericin-B, trimethoprim-sulfamethoxazole, and rifampicin. This regime has been found to be effective in the treatment of a similar case reported earlier. A long-term sequel could not be monitored as they were lost to follow-up after discharge from the hospital. The current series of cases highlights the importance of including GAE in the differential diagnosis of patients with chronic as well as acute and sub-acute CNS syndrome with no apparent cause. A high index of suspicion should be maintained even in immunocompetent persons without any history of swimming. It will help in more aggressive diagnosis, understanding of associated risk factors and early therapeutic interventions.

PMC6223070_01

Male

A 53-year old white male was referred to University Hospital Limerick with a macular rash on extensor aspects of upper limb and torso, bilateral loin pain, arthralgia, fatigue, active urinary sediment and acute kidney injury in August 2015. The current presentation was preceded by two previous episodes of illness in which he had reported similar symptoms along with haemoptysis in April and July 2014. Past medical history revealed the presence of a peripapilary melanoma of the left eye treated with radiotherapy in 2010 and a basal cell carcinoma of the mid-back excised in 2000. The patient denied tobacco use and drank occasionally and denied any family history off kidney disease. He worked on a farm and was married with two children. On presentation his blood pressure was 124/70 mmHg, weight 91 kg, and there was evidence of macular rash on his back but no lower limb oedema. Urine evaluation demonstrated activity with 3+ protein and 3+ blood, and his serum creatinine was elevated at 128 mumol/L compared to a baseline of 116 mumol/L recorded in April 2014. Serology was positive for P-ANCA with a titre of 160 and he had an anti-MPO titre of over 200 units/mL; apart from this ANA was positive with a titre of 1600 with negative Anti-dsDNA, Anti-Sm, Anti-Sm/RNP and Anti-SSB/RO/LA; Serology for HIV 1 + 2 Ag/Ab and Hepatitis BsAg & Hepatitis C antibody were negative; complement levels were within normal range C3 of 0.82 g/L and C4 of 0.24 g/L. ESR was 30 mm/h and Hs-CRP was 48 mg/L; rest of his routine bloods were unremarkable (White cell count 5.8 x 109/L, haemoglobin 13.5 g/dL, neutrophils 4.00 x 109/L, platelet 210 x 109/L, sodium 141 mmol/L, potassium 4.2 mmol/L, total protein 69 g/L, albumin 39 g/L, serum calcium 2.31 mmol/L, serum phosphate 1.09 mmol/L, bilirubin 7.3 micromol/L, alkaline phosphatase 81 IU/L, gamma-glutamyl transferase 25 IU/L, alanine-aminotransferase 39 IU/L, prothrombin time 12.0 s, activated partial thromboplastin time 32.0 s). Chest X-ray was normal. A recent ultrasound of his kidneys demonstrated normal size and shape with normal cortex. A native kidney biopsy revealed evidence of moderate arteriosclerosis with 30-35% fibrosis, areas of thrombotic microangiopathy but without evidence of fibrinoid necrosis or epithelial crescents. Immunofluorescence was negative and electron microscopy revealed thin glomerular basement membranes with mean measurements less than 250 nM and many measurements less than 200 nM, consistent with thin basement membrane disease (TBMD). Based on the presence of an AKI with active urine sediment, associated skin rash, and positive serology with high titres of P-ANCA and anti-MPO along with an antecedent history of haemoptysis, we diagnosed an ANCA-associated vasculitis likely microscopic polyangiitis (MPA) based on the European Medicines Agency Algorithm, although the kidney biopsy sample failed to demonstrate classical features of renal vasculitis. Treatment was initiated with corticosteroids and intravenous rituximab infusions (at day 0 and day 18) with prophylaxis for pneumocystis (co-trimoxazole), osteoporosis (oral Vitamin D3 and bisphosphonates), and gastritis (proton pump inhibitor). Four weeks later his urine sediment normalised with no detectable blood or protein; his CRP fell to < 5 mg/L and his ANCA titres fell to 40 but his anti-MPO level remained remarkably high 198 IU/mL. Two months later, he developed severe depression attributed to steroids requiring taper and the initiation of anti-psychotic therapy. Six months following initial presentation, his vasculitis remained clinically quiescent and the patient was commenced on azathioprine (AZA) as a steroid sparing agent for maintenance immunosuppression. Two weeks after AZA commencement, the patient presented to the emergency department with acute painful disseminated morbilliform rash along with fever and myalgia. On examination temp was 39.7 C and a widespread indurated erythematous papular rash was noted (Fig. 1a, b). An extensive viral and immunologic work up was negative including virology for herpes zoster, and simplex. Considering his history of immunosuppression he was empirically started on acyclovir. Full blood count revealed neutrophilic leucocytosis with neutrophil count of 12.2 x 109/L, Hs-CRP 259 and ESR 59, and a stable serum creatinine concentration of 115 mumol/L. A full septic work up was negative including negative serology for HIV, hepatitis A, B, C, and CMV. A skin biopsy was diagnostic of Sweet's syndrome, in which the affected lesions revealed extensive neutrophilic infiltrate in the dermis but without evidence of leukocytoclastic vasculitis, herpes, zoster, or erythema multiform. Azathioprine was stopped and the patient was treated with oral prednisolone (30 mg once daily followed by a steroid taper) and colchicine (500 mcg twice daily). Within 4 weeks, the rash had completely resolved (Fig. 1c, d) and his inflammatory markers normalised. As the onset of symptoms were temporally related to initiation of AZA, a diagnosis of drug-induced Sweet syndrome. His steroid dose was tapered gradually to zero and treatment with colchicine was continued. As of August 2017, his vasculitis remains quiescent and there has been no recurrence of Sweet syndrome, however his ANCA titres remain elevated with anti-MPO levels 170 RU/mL.

PMC4350223_01

Female

At 38-weeks gestation a 31-year-old primigravida presented with diplopia on left gaze of 1- day duration. The diplopia was worse for far objects. She had unilateral throbbing headache similar to her previous migraines for 3 days prior to admission, associated with two to three episodes of vomitting per day, which were similar to her previous migraine attacks. There was no history of fever, photophobia or phonophobia. She had an uneventful follow-up in antenatal clinic throughout the pregnancy. Her blood pressure was normal at the 13 week, 20 week and 33 week follow up visits. Her urinalysis was normal and she was not diabetic. There was no significant past medical or family history. She was non-smoker, non-alcoholic and there was no history of substance abuse. Preeclampsia was ruled out and she was referred to neurology with above history on the same day of admission. On examination, she was alert and oriented. Her blood pressure was 106/65. There was complete paralysis of the left lateral rectus muscle. She had hyper-reflexia in all four limbs (Deep tendon reflexes were 3+). Rest of the neurologic examination was normal. MRI brain showed a non-enhancing, central, symmetrical, pontine T2 hyper-intensity which also showed evidence of restricted diffusion [Figure 1a and b] consistent with central pontine myelinolysis (CPM). The MRI of orbits, MR angiogram and MR venogram were unremarkable. Blood investigations including full blood count, ESR, renal, liver and thyroid function tests, folate, Vitamin B12, calcium and phosphate were normal. Serial daily electrolytes did not reveal any derangement. Toxicology and autoimmune workup included were negative. Lumbar puncture opening pressure was normal and CSF was unremarkable. (WBC = 0; Proteins = 0.24g/; Glucose normal; Gram stain, bacterial culture, fungal smear and culture, TB-PCR and TB-culture negative, oligoclonal bands negative). Patient underwent Caesarean section. A healthy baby weighing 3180 g was delivered. Considering the diagnosis of CPM due to typical lesion, absence of obvious secondary cause and mild symptoms and signs, she was observed without any specific treatment. She gradually improved and the left eye abduction movement had recovered to about 50% at the time of discharge 4 days after the delivery. At 2-week follow-up after discharge, she was asymptomatic and her VI nerve palsy had fully recovered. A repeated MRI at this time showed complete resolution of the previous changes. [Figure 2]

central pontine myelinolysis, isolated sixth nerve palsy, pregnancy, third trimester

PMC4327556_01

Male

A 59-year-old man with an unremarkable medical history presented with an acute state of confusion, fever and two episodes of generalized tonic-clonic seizures on that day. On admission, the patient was febrile (tympanic temperature of 38.1 C), his blood pressure was 137/79 mm Hg with a pulse rate of 103 beats/min, his respiratory rate was 16/min, and his oxygen saturation was 98% at room air. There were no murmurs or other abnormalities on cardiac auscultation, and examination of the respiratory system, the abdomen and anogenital region was normal. The neurological examination revealed psychomotor inhibition and left homonymous hemianopsia, without any motor abnormalities or other neurological deficits. There were no abnormalities found on the laboratory studies (hemoglobin 15.23 g/dl, white blood cell count 8.70 x 103/mul, C-reactive protein 0.5 mg/dl, erythrocyte sedimentation rate 11 mm/h), including negative results on the immunological study, seronegative status for HIV and negative serological tumor markers. A brain magnetic resonance imaging (MRI) scan revealed a single, large, right, frontoparietal lesion. Cerebrospinal fluid analysis showed no abnormalities, including negative results for DNA of HSV 1 and 2, Mycobacterium tuberculosis, toxoplasmosis, and JC virus. A repeated brain MRI scan showed a worsening of the lesion, and the hypothesis of brain abscess was strongly considered (fig. 1). Treatment with ceftriaxone (2 g i.v. every 12 h) combined with metronidazole (500 mg i.v. every 6 h) and dexamethasone (5 mg i.v. every 8 h) was started. Seizures were controlled with levetiracetam (500 mg p.o. every 12 h). There was no evidence of paroxysmal activity on the electroencephalogram, and contrast-enhanced computed tomography of the chest, abdomen and pelvis resulted negative. Blood and urine cultures were obtained before starting antibiotic therapy, also with negative results. Endocarditis was ruled out by a normal transesophageal echocardiogram. After 4 weeks of antibiotic therapy, although the neurological exam was normal, the patient again became febrile and symptomatic, complaining of a severe headache that evolved for 4 days, throbbing in nature and precipitated by Valsalva maneuver. Another brain MRI was performed, with evidence of further worsening of the lesion (fig. 2). Given the lack of evidence of a resolution of the lesion and the persistence of neurological symptoms, surgical drainage was performed with isolation of S. lugdunensis. The antibiogram of the isolated microorganism disclosed susceptibility to trimethoprim-sulfamethoxazole, methicillin, gentamicin, and erythromycin. Transesophageal echocardiogram and blood cultures were then repeated, again with negative results. Treatment with trimethoprim-sulfamethoxazole (5 mg/kg p.o. every 6 h) was performed during 12 weeks with a good response. There was also a favorable imaging response, with brain MRI undertaken a month after starting this therapy revealing almost complete resolution of the brain abscess (fig. 3). After 6 months of follow-up, the patient remains asymptomatic, and his neurological exploration is unremarkable.

brain abscess, coagulase-negative staphylococcus, staphylococcus lugdunensis

PMC3350099_01

Male

A 23-year-old Malay gentleman factory worker presented with generalised headache for one-month duration. It was associated with nausea and vomiting. He experienced painless progressive blurring of vision of the right eye two weeks later which he described as inferior visual field defect. He had loss of appetite and significant reduced weight but no night sweats or hemoptysis. Otherwise, there was no history of contact with pulmonary tuberculosis patient, drug abuse, blood transfusion, and high-risk behaviour. He has no other medical illness. His visual acuity on the right eye was 6/45 and improved to 6/15 with pinhole. There was no relative afferent pupillary defect. The right eye showed mild vitritis with no anterior chamber reaction. Right fundus examination revealed a choroidal raised lesion, yellowish in colour at the centre with pinkish fluffy edges, measuring one and a half disc diameter, and located at one disc diameter away from optic disc superiorly (Figure 1). The arcades vessels appeared tortuous and dilated with perivascular sheathing at supero- temporal and nasal arcade. The optic disc looked swollen and hyperaemic with gliosis at inferonasal disc margin. The left eye was normal. Systemic examinations revealed no cervical, axillary, or inguinal lymphadenopathy. The respiratory, cardiovascular, and central nervous systems examination remained no abnormalities. The ultrasonography of the right eye showed no evidence of retinal detachment, acoustic hollowing, or uveal excavation to suggest choroidal melanoma. The chest radiograph revealed no focal lesion or consolidation to suggest pulmonary tuberculosis. Mantoux test showed reading of 22 mm. Full blood count result showed that no significant finding with erythrocyte sedimentation rate (ESR) was 14 mm/h. Serum toxoplasmosis of IgM and IgG was negative. The syphilis and retroviral serology were nonreactive, and connective tissue results also inconclusive. The computerized tomography (CT) scan of the brain and orbit revealed multiple ill-defined peripherally enhancing iso to hypodense lesions with perilesional edema at right frontal and left temporal lobe consistent with cerebral abscesses (Figure 2). A clinical diagnosis of right choroidal tuberculoma with multiple cerebral abscesses suggestive of tuberculosis infection was made. He was treated with antituberculosis chemotherapy for one year which divided into intensive phase for three months (tablet ethambutol 1200 mg daily, tablet pyrazinamide 1500 mg daily, tablet isoniazid 300 mg daily, tablet rifampicin 600 mg daily, and tablet vitamin B6 10 mg daily) and maintenance phase for nine months (tablet isoniazid 900 mg biweekly, tablet rifampicin 600 mg biweekly, and tablet vitamin B6 10 mg biweekly) by chest physician. On follow-up, the repeated CT scan of the brain after three months of antituberculosis drugs showed resolved cerebral abscesses. At the same time, his right visual acuity was improved to 6/6 and choroidal tuberculoma of the right fundus appeared to have well-defined margin with adjacent retinal striae. At one-year follow-up, the choroidal tuberculoma resolved completely with scar formation and significant macular striae (Figure 3).

PMC7591938_01

Female

A 27-year-old female with a history of bipolar 1 disorder, borderline personality disorder, posttraumatic stress disorder (PTSD), previous history of multiple suicide attempts, T2DM, and obesity (weight 160 kg; body mass index 56 kg/m2) status-postsleeve gastrectomy in 2016 presented to the emergency department (ED) following a suicide attempt. She was brought to the ED by self-notifying emergency services after having shortness of breath and dizziness following self-injection of 900 units of insulin glargine U-100 (Lantus ) subcutaneously into her abdomen three hours prior. This represented her third intentional insulin overdose in the preceding six months. She was previously insulin-requiring, on Lantus, but was weaned off insulin four years ago after sleeve gastrectomy and subsequent 68 kg weight loss over the preceding five years. The patient's most recent hemoglobin A1c (HbA1c) ten months prior to presentation, while off insulin or any other hypoglycemic agents, was 4.7%. Home medications at this time included duloxetine 120 mg daily, bupropion 300 mg daily, lithium 900 mg daily, prazosin 5 mg at bedtime, trazodone 150 mg at bedtime, and mirtazapine 30 mg at bedtime. The patient reported suicidal ideation and worsened depression for three months prior to presentation and decided to inject three full insulin glargine U-100 pens (300 units each), which she had at home from her prior insulin prescription. The initial fingerstick blood glucose taken by paramedics prior to arrival to the ED was 131 mg/dL. At that time, she was closely monitored, but not medically treated, and was sent to the ED. Her fingerstick blood glucose level upon presentation to the ED was 113 mg/dL, at which time she was somnolent but arousable and answering questions appropriately. Her physical examination upon arrival was unremarkable and did not reveal any areas of fluctuance at the reported injection sites. Figure 1 depicts the patient's course of therapy from the time of ED presentation. An intravenous (IV) 10% dextrose (D10) infusion was started at 300 mL/hour 30 minutes after ED arrival to prevent hypoglycemia. A regular diet was started and carbohydrate intake was encouraged. Fingerstick glucose levels were monitored every 15 minutes for the first seven hours and every 30 minutes thereafter. The patient's blood glucose readings first approached the hypoglycemic range of <70 mg/dL approximately three hours after presentation (fingerstick blood glucose = 74 mg/dL). She received two 50-gram ampules of dextrose 50% (D50) IV, along with three 1 mg doses of intramuscular (IM) glucagon, over the next four hours in addition to the D10 IV infusion. The patient was then transferred to the medical intensive care unit (MICU) for close observation. Due to persistent hypoglycemia and inability to wean the D10 IV infusion, a standing order for glucagon 1 mg IM for blood glucose <70 mg/dL was added. During the first 48 hours of her admission, she required eleven 1 mg IM glucagon doses in addition to the D10 IV infusion but continued to experience hypoglycemia with the lowest recorded blood glucose reading of 64 mg/dl. She was transitioned from a standard diet to a bariatric diet due to suspected reactive hypoglycemia associated with her postbariatric surgery status, which consisted of 56 grams of carbohydrate and 18 grams of protein per day. An IV glucagon infusion was started at 1 mg/hr on hospital day two (approximately 44 hours after presentation) in a continued effort to minimize IV fluid volume. In addition, a trial dose of hydrocortisone 100 mg IV bolus was given at the time the IV glucagon infusion was started. The IV glucagon infusion was titrated to 2 mg/hr as the D10 IV infusion was weaned off, which was done on hospital day three (approximately 73 hours after presentation). However, the patient's glucose levels began trending towards the hypoglycemic range, requiring further titration of the IV glucagon infusion to 4 mg/hr. Hydrocortisone 100 mg IV every 8 hours was then started to reduce the IV and IM glucagon requirements. The IV glucagon infusion was weaned off on hospital day four after three additional doses of hydrocortisone on days 3 and 4. The patient became hyperglycemic following the last dose of hydrocortisone (blood glucose = 309 mg/dL), which prompted discontinuation of the stress-dose steroids. Following discontinuation of medical therapy for hypoglycemia, her blood glucose ranged from 130 to 150 mg/dL, and the patient was transferred out of the MICU to a medical floor for observation without recurrence of hypoglycemia.

PMC6125766_01

Female

A 42-year old woman who underwent a left thoracotomy for a mediastinal lesion of unknown pathology 20 years ago, was referred to our medical center with one day of mild hemoptysis. She had neither chest pain nor shortness of breath. She was diagnosed with a simple aspergilloma on radiologic imaging few years ago and has been having an episodic productive cough for which multiple courses of antibiotics were prescribed. She also had a similar episode of mild hemoptysis one and a half year prior, which self-resolved. The patient was afebrile, appeared comfortable and was hemodynamically stable. Chest auscultation was unremarkable. A chest radiograph showed a retro-cardiac opacity. An enhanced computed tomography (CT) of the thorax showed a left lower lobe fungus ball with a meniscus sign, consistent with a simple aspergilloma (Fig. 1). These findings were unchanged when compared to previous scans. A flexible bronchoscopy was performed and revealed a small amount of blood oozing from the left lower lobe with no visible endobronchial lesions. Cytology on bronchoalveolar lavage taken from that lobe showed benign bronchial cells and few red blood cells. Respiratory cultures grew 60,000 colonies of pan-susceptible Pseudomonas aeruginosa and were negative for tuberculosis. IgG and precipitins against Aspergillus were also negative. In view of her presumed diagnosis of aspergilloma coupled with recurrent hemoptysis, the patient underwent wedge resection of the left lower lobe lesion. Examination of the specimen showed a white gauze impacted within a dilated bronchus, with peribronchial fibrosis, inflammation and hemorrhage (Fig. 2).

Transverse section of a thoracic CT-scan showing what appears to be a "fungus ball" within a cavity in the anterior aspect of the lateral bronchopulmonary segment of the left lower lobe.

PMC4487547_01

Female

Svoboda and Richards and Savage and Svoboda demonstrated the successful introduction of a commercial smartphone to aid both prospective and retrospective memory difficulties in a woman (RR) with moderate to severe memory impairment. Not only did RR acquire the skills to use the smartphone calendar for targeted PM tasks, but she generalised the skill to prompt everyday activities and learned to use other applications, e.g., video games and to do lists. They supplemented their original ABAB design with an 18-month follow-up study and found that RR continued to use the smartphone with similar success rates to immediately after the initial intervention and at 4-month follow-up. However, completion of memory tasks reduced when an alternative smartphone (with no training) was used. They note that training in the use of the smartphone may generalise within brands but not across different brands. In a second single case ABAB design, Svoboda et al. demonstrated the benefits of a smartphone, in particular the calendar feature, for an 18-year-old woman with severe memory difficulties who had sustained her injury at the age of 13 years. They found that the rate of completing tasks (e.g., making phone calls at the correct time or attending social events) was significantly increased using the smartphone when compared to baseline. Furthermore, use of the smartphone reduced carer strain and improved her quality of life. Svoboda et al. went on to demonstrate the success of their training protocol in 10 individuals with memory problems of varying aetiology who were taught to use either PDAs or smartphones to cue a series of phone calls or everyday memory tasks. Significant improvement was found in day-to-day memory functioning for all 10 participants and, again, some individuals generalised the training to other software applications on the devices. Thus, studies so far suggest that mobile and smartphones, in particular the use of text message alerts, are effective in people with memory problems. There are a variety of memory applications (apps) and software packages that can be used with smartphones, such as Google Calendar (used in the present study), Microsoft office calendar and Zoho Calendar. McDonald, Haslam, Yates, Gurr, Leeder, and Sayers also explored the use of Google Calendar in 12 people with ABI (TBI, stroke, anoxia, viral infection or heart attack). This was a randomised controlled crossover study comparing the effectiveness of Google Calendar with a standard paper diary. They found that both aids improved recall of prospective memory tasks, however, Google Calendar was found to be significantly more effective than the paper-based diary. Participants highlighted that the timed text message alerts were the most beneficial feature of the calendar system, as they provided a written visual prompt as well as the auditory alert. In the latter study participants had all used memory aids prior to the study. In the present study we explore whether Google Calendar is an effective memory aid for a man (JA) with severe verbal and visual memory difficulties and impaired executive functioning who did not use any memory aids prior to his injury and was initially very unwilling to use any aid subsequent to his injury. Google Calendar was eventually chosen over other forms of memory aid after a detailed assessment that included factors influencing acceptability to JA.

acquired brain injury, google calendar, prospective memory, single case experimental design

PMC8709544_01

Female

A 25 year old primigravida woman whose gestational age from LNMP was 25 weeks plus six days presented for the first time with a chief complaint of involuntary abdominal movement of three weeks duration. She stated that three weeks prior to her presentation to the clinic she had experienced involuntary, rhythmic and painful abdominal movement (Supplementary Video 1) (Supplementary Video 2) which started suddenly and stays for 30-120 seconds and happens 3-5 times per day. Most of the time, it starts while she was eating food and stops when she was breathing deeply and distracted. Other than these she did not find any predisposing, exacerbating or relieving factors. She presented to the antenatal clinic with these complaints and on arrival the obstetrician had also noticed the rhythmic involuntary abdominal movement as showed in the Supplementary Videos 1 and 2. She denied the use of any medication preceding the involuntary abdominal movement except ferrous sulphate given during ANC visit. She never had any gynecologic and surgical procedure before. Different laboratory and imaging investigations were done for her. These are renal function test, liver function test, thyroid function test, electrolytes, HIV, Venereal Disease for Research Laboratory (VDRL) and CBC and all were within the normal limit. Ultrasound examination revealed 27 weeks singleton intrauterine pregnancy without any abnormal finding. Imaging like MRI, EEG and EMG was not done since it is not available in this locality (Harar) and it was difficult for her to go to the capital city of the country (Addis Ababa) which is 580 kilometers away from Harar town where these imaging services are available. On physical examination vital signs and all the system examination were unremarkable except the abdominal examination which shows a 26 week sized gravid uterus with positive fetal heartbeat. She was diagnosed with belly dancer dyskinesia and diazepam was prescribed but she refused to take it. At 38 weeks plus five days she was diagnosed with preeclampsia with severity features after she presented with severe headache of two days duration and her BP was 150/100 mmHg for which cervical ripening and induction was started. After 10 hours of total induction time there was no contraction, so she was taken to operation theater and undergone cesarean section for the indication of failed induction to result in delivery of a 4000 g female live neonate who cried immediately after delivery. She was discharged after 48 hours post-cesarean section hospital stay with good post-partum condition and a healthy neonate. During the post-partum period, she did not have this abnormal movement and 6 months after her first delivery, she came to the clinic for antenatal follow-up after she had an unplanned but wanted pregnancy. Her second pregnancy antenatal follow-up was uneventful without any abnormal symptom unlike the previous pregnancy. At 39 weeks of pregnancy from her early ultrasound she underwent elective cesarean section for the indication of short inter-pregnancy interval and previous cesarean section. After two postpartum days of hospital stay, the mother and neonate were discharged healthy.

ethiopia, harar, belly dancer dyskinesia, case report, pregnancy

PMC6744749_01

Male

A 47-year-old male with seronegative human immunodeficiency virus (HIV) and diabetes mellitus suffered from lower back pain. He was diagnosed with bacterial spondylitis and iliopsoas abscess [Figure 1a]. Multiple antibacterial agents were prescribed, but the lesion did not disappear. M. tuberculosis was detected from the abscess, and caseous granuloma was identified pathologically in surgical specimens of the intervertebral disk [Figure 1b]. He was prescribed the antituberculous agents which were isoniazid 300 mg, rifampicin 600 mg, ethambutol 1000 mg, and pyrazinamide 1500 mg/day. His lower back pain and inflammatory findings improved by the antituberculous therapy. Two months after starting the antituberculous therapy, he complained of headache, nausea, and staggering. Physical findings on admission were that he was afebrile and did not have stiff neck. A right coordination deficit was identified, and other neurological deficits did not exist. Laboratory findings did not show inflammatory reaction. Chest computed tomography (CT) did not show any cavity lesions. Magnetic resonance (MR) images revealed a nodular enhanced lesion in the right cerebellar hemisphere extending to the vermis associated perifocal edema and bilateral ventriculomegaly [Figure 2]. The lesion showed hypointensity by diffusion- attenuated, weighted images. Tuberculoma was suspected which appeared de novo or enlarged during the antituberculous therapy that was suggested to be a PR. The therapeutic strategy was a lesionectomy because he presented noncommunicating hydrocephalus, and malignant glioma could not be ruled out completely. Lesionectomy would be thought to relief noncommunicating hydrocephalus, and we did not plan to perform ventricular shunt. Surgery was performed by a midline occipital approach. A well-circumscribed mass with gray color was identified by opening the cerebellomedullary fissure [Figure 3]. A mass of 3.5 cm was extracted [Figures 3 and 4]. Pathology revealed a caseous granulomatosis at low-power magnification and invasion of lymphocytes and macrophages at high-power magnification [Figure 4a], and those were suggestive findings of past infection of M. tuberculosis. M. tuberculosis was not identified by Ziehl-Neelsen stain. These findings lead to a definitive diagnosis of tuberculoma. Postoperative MR images revealed total removal of the lesion [Figure 4b]. He recovered well from nausea and staggering and was discharged 3 weeks after the operation. He was prescribed antituberculous agents which were isoniazid, rifampicin, ethambutol, and pyrazinamide for the first 2 months and then isoniazid and rifampicin for up to 10 months according to the guideline for the treatment of tuberculosis of central nervous system.

anti-tuberculous therapy, cerebellar tumor, paradoxical reaction, pott’s disease, spinal tuberculosis, tuberculoma

PMC6122386_01

Male

An 84-year-old white male was referred to us for anemia and thrombocytosis. He had a history of hypertension and dyslipidemia, for which he took enalapril and lovastatin. He lived and worked on a ranch in far west Texas. He had been fatigued for a few months. Physical exam showed mild conjunctival pallor. Liver and spleen were not palpable. Rest of the physical exam was unremarkable. Complete blood count (CBC) showed a white blood cell count of 9600/microl (4000-10,000) with a normal differential, hemoglobin of 9.9 g/dl (13.5-17.5) with MCV (mean corpuscular volume) of 108 fl (80-95). Platelet count was 986,000/microl (150,000--450,000). Peripheral blood smear showed macrocytosis, moderate anisopoikilocytosis and marked increase in platelets. Prothrombin time and activated partial thromboplastin time were normal. He then underwent a bone marrow biopsy and aspirate. This showed a cellularity of 50%. Megakaryocytes were increased (Fig. 1). Myeloid erythroid ratio was normal. There was no increase in fibrosis. Blasts were 1-2%. Iron stain showed 15-20% ring sideroblasts (Fig. 2). Cytogenetic studies showed a deletion of the long arm of chromosome 5 in all twenty metaphases analyzed. Eleven of those cells also had a deletion of the long arm of chromosome 20 (Fig. 3). Molecular studies did not show JAK2 mutation or BCR/ABL rearrangement. A CALR exon 9, frame shift mutation (c1103_1130del37) was detected. No mutations were detected in CSF3R, SRTBP1, MPL or SF3B genes. Patient was initially started on hydroxyurea for cytoreduction. Once the results of cytogenetic studies became available, hydroxurea was discontinued and lenalidomide (10 mg) was initiated. After a transient period of worsening anemia, his CBC improved and by 3 months his peripheral blood counts were normal (Fig. 4). Fluorescent in situ hybridization and PCR studies on peripheral blood, performed 6 months after diagnosis, did not detect 5q deletion, 20q deletion or CALR mutation, suggesting molecular remission. At last follow up at 2 years, patient has continued to stay on lenalidomide and has a normal CBC.

5q, lenalidomide, mds/mpn, ring sideroblast, thrombocytosis

PMC7199827_01

Male

A 30-year-old male patient was referred to our eye clinic from an external center with an IOFB in his right eye. A small piece of iron shaving sprung into his right eye while he had been striking a nail with a hammer. He had been told that he had a foreign body in his eye and that he should have undergone vitrectomy; thus, 1 mg vancomycin+2 mg ceftazidime was injected into his eye. On ophthalmologic examination, visual acuity in his right eye was 0.2 (Snellen), and a lamellar corneal cut with negative Seidel test in the right cornea in the area corresponding to the upper edge of the pupil was observed. Perforation on the anterior capsule of the crystalline lens and opacification of the lens material that protruded from the capsule to the anterior chamber were observed. The details of the ocular fundus were not selected. Retinal detachment was not observed in Ultrasonography. On orbital tomographic examination, an image of 1.5x1.5 mm consistent with a metallic object was observed in the intraocular area, close to the equator (Fig. 1). The left eye was emmetropic without loss of its visual acuity. Moxifloxacin eye drops (8x1/d) and oral ciprofloxacin (500 mg tb bid) were given to the patient. Under general anesthesia (UGA) cataract surgery, IOL placement and PPV were planned in the same session for removal of IOFB. UGA after local antisepsis, blepharostat was placed to keep the eyelids open. The conjunctival sac was irrigated with 5% povidone-iodine solution. Transconjunctival sclerotomies were prepared from 3.5 mm away from the limbus using a 23-gauge trocar. Corneal side accesses were performed at the 10 and 2 o'clock positions using a 20-gauge MVR. The anterior capsule was stained with trypan blue after air was insufflated into the anterior chamber. The anterior chamber was filled with a viscoelastic (VES) material. It was entered with a clearcorneal incision at the 12 o'clock position. Anterior capsulectomy was performed, and the opacified lens material was removed by aspiration/irrigation. A 2x2 mm gap was detected in the posterior capsule. A foldable IOL was placed inside the capsule. The main corneal incision was closed with a 10/0 nylon suture. The anterior chamber was completely cleared from VES. An infusion cannula was inserted into the previously placed trocar in the inferior temporal region. During PPV used a wide field visualizing system (EIBOS). An IOFB on the equatorial region hanging close but not touching the retina was observed without haze in the vitreous. With the aid of endoillumination through the trocar in the upper temporal area, an ocutome was passed through the trocar in the upper nasal area into the vitreous area. So as not to cause traction during the removal of IOFB, the vitreous tissue around the IOFB was scraped to create a tunnel-shaped cavity between the ocutome, trocar tip, and IOFB in the vitreous tissue. After removal of the trocar in the upper nasal region and dilation of the sclerotomy site, the foreign body was picked up and extracted through the enlarged sclerotomy path. With this approach, approximately 1-2/8 parts of the vitreous were extracted, and 6-7/8 parts of it were left in situ. Retinal tamponade was not used. After removal of the foreign body with dimensions of 1.5x1.5x0.5 mm, sclerotomies were closed with 8/0 vicryl sutures, and subconjunctival injections of gentamicin and onadron were performed. The patient was discharged with a prescription of eye drops of moxifloxacin (0.5%, 8x1/d)+prednisolone sodium phosphate (10 mg/ml, 4x1/d) and tropicamide (1%, 1x1). Doses of drug therapy were gradually reduced and discontinued after 35 days. On postoperative months 1, 3, 7, and 30 and 2, 3, and 4, the pupil was regular, the IOL was centralized (Fig. 2), the retina was attachedand the fundus, and the macula was observed naturally (Fig. 3). Endophthalmitis or severe inflammation were not observed. Intraocular pressure was 17 mm Hg.Visual acuity was -1.50 to 10/10 at all visits.

dislocated intraocular lens, intraocular foreign body, minimal, pars plana vitrectomy, partial

PMC9846127_01

Female

This study included 172 males and 87 females, with a sex ratio of 1.98. The median age of the 259 patients was 33 years, and the AHO patients had a median age of 16 years; CHO patients had a median age of 41 years. The analysis revealed that there was a significant difference in the age of onset between the AHO and CHO patients (p<0.001), and the age of onset in the AHO patients was younger than that in the CHO patients. Among the 259 patients divided by age group, the top three age groups were 11-15 years old (36 patients), 6-10 years old (25 patients),and 61-65 years old (25 patients), 46-50 years old (24 patients). After being divided according to whether they had AHO or CHO, the age groups with the highest incidence were the 11-15 years old (22 patients) and 61-65 years old (22 patients) groups Table 1 . The total numbers of infections in the extremity and trunk sites were 252 (97.30%) and 7 (2.70%), respectively. Among all 259 infections, 246 (94.98%) were single infection, and 13 (5.02%) were multisite infections. The tibia (79 cases, 32.11%) was the most common site of solitary infection, followed by the femur (64 cases, 26.02%) and phalanges (20 cases, 8.13%) ( Figure 1 ). Before admission, 68 patients had a history of fever, accounting for 26.25% of the total. Among them, 42 patients had fever before admission in the AHO group, accounting for 43.75% of the total number of patients with AHO, and 26 patients had fever before admission in the CHO group, accounting for 15.95% of the total number of patients with CHO. The difference was statistically significant (p=0.018). The number of febrile patients was significantly higher in the AHO group than in the CHO group. Before admission, 85 patients had a history of antibiotic use, accounting for 32.82% of the total, and most of these patients had taken cephalosporins (injection or oral administration). Etiology analysis revealed that most cases of HO had no obvious cause (183/259, 70.66%); the number of cases caused by soft tissue injury (fall, abrasion, bruise, crush and crush) (34/259, 13.13%) followed the number of cases with no obvious cause. Exercise-induced illness (skipping, dancing, swimming, basketball sprain) and history of heavy physical labor (13/259, 5.02%) was the third most common cause. In addition, some patients exhibited a history of infection before onset (upper respiratory tract infection, chickenpox infection and skin infection); high fever (13/259, 5.02%); a history of being stabbed, punctured or injected (10/259, 3.86%); bite history (5/259, 1.93%); and a history of allergic purpura (1/259, 0.39%)( Figure 2 ). As shown in Table 2 , among the preoperative (upon admission) serum inflammatory markers, the rate of ESR positivity was the highest at 67.58% (148/219), followed by hs-CRP at 66.67% (132/198), and the rate of WBC positivity was at 24.90% (63/253). According to the AHO and CHO classifications, the rates of positivity for WBC were 38.30% and 16.98%, the rates of positivity for hs-CRP were 69.33% and 65.04%, and the rates of positivity for ESR were 75.61% and 62.77%, respectively. There were significant differences between the AHO and CHO patients in the WBC levels, and the AHO patients had a higher WBC count than the CHO patients (p<0.001). The baseline age of the AHO patients was significantly younger than that of the CHO patients (p<0.001). To reduce the age-induced bias, we performed age-adjusted analysis. After adjusted, positive rate of ESR showed significant difference (p = 0.014). The manifestations of inflammation were divided into redness of the skin, swelling, fever, pain and dysfunction according to the consultation and physical examination upon admission. Pain affected the highest number of patients at 222, which was followed by 175 patients with swelling and 44 patients with functional impairment. There were significant differences in the incidence of redness of the skin, swelling, fever, and dysfunction between the AHO and CHO patients (p<0.05), and these clinical symptoms were more common in the AHO patients than in the CHO patients. The baseline age of the AHO patients was significantly younger than that of the CHO patients (p<0.001). To reduce the age-induced bias, we performed age-adjusted analysis. After adjusted, positive rate of swelling symptom showed no significant difference (p = 0.066). In our study, a total of 171 patients had documented pathogen cultures. The rate of positivity among all cultures was 71.93% (123 cases), of which 78.86% (97 cases) involved single microorganism infections. Among those with single microorganism infections, Gram-positive bacteria accounted for 86.60% (84 cases), Gram-negative bacteria accounted for 13.40% (13 cases), and SA accounted for 63.92% (62 cases), including MSSA 56.70% (55 cases) and MRSA 7.22% (7 cases). Among the polymicrobial infections, 46.15% (12 cases) involved only Gram-positive bacteria, 11.54% (3 cases) involved only Gram-negative bacteria, and the rest were mixed bacterial infections. As shown in Table 3 , among the 202 strains of pathogenic microorganisms detected, 160 strains were Gram-positive bacteria, 41 strains were Gram-negative bacteria and 1 strain was fungi. The top three were MSSA with 100 strains (49.50%), MRSA with 13 strains (6.44%), and MRSE with 9 strains (4.46%). The top three pathogenic bacteria in the AHO group were 53 strains of MSSA, 8 strains of MRSA and 3 strains of MRSE. SA accounted for 75.61% (31/41) of the single microorganism infections in AHO patients. The top three pathogenic bacteria cultured in the CHO patients were 47 strains of MSSA, 6 strains of MRSE and 6 strains of Enterobacter cloacae. SA accounted for 55.36% (31/56) of the single microorganism infections in the CHO patients. Through the analysis of drug susceptibility results it was observed that, among the Gram-positive bacteria ( Table 4 ), MSSA was most sensitive to linezolid (99%), followed by vancomycin (98%), oxacillin (98%) and rifampicin (98%). The MRSA strains were most sensitive to linezolid (100%), vancomycin (100%), and rifampicin (100%). The MRSE strains were most sensitive to linezolid (100%) and vancomycin (100%). Regarding Gram-negative bacteria ( Table 5 ), E. cloacae was most sensitive to aztreonam (100%) and piperacillin/tazobactam sodium (100%). Escherichia coli was most sensitive to piperacillin/tazobactam sodium (100%). Pseudomonas aeruginosa was most sensitive to ciprofloxacin (85.71%) and imipenem (85.71%). The treatment of hematogenous osteomyelitis usually includes conservative treatment and surgical treatment. Surgical treatment is usually divided into debridement (including simple debridement, debridement plus drip drainage, and debridement plus VSD suction), bone cement (nonabsorbable bone cements, such as PMMA; absorbable bone cement, such as calcium sulfate (CS); and calcium phosphate/calcium sulfate (CS/CP)) and amputation in some patients with severe infections ( Table 6 ). Regarding the antibiotics given on admission, 235 patients (90.73%) received intravenous antibiotics, and 24 patients (9.27%) received oral antibiotics. Regarding intravenous antibiotic therapy, 96 patients (40.85%) received single antibiotic therapy, of which cefazolin (25 patients,26.04%) was the most commonly used antibiotic. All patients were followed up for at least 12 months; 31 patients (11.97%) were lost to follow-up, and 18 patients (6.95%) had amputations in the hospital. A total of 189 patients(90%) were in remission, and 21 patients (10%) were in relapse. Among them, after conservative treatment, the remission rate was 90%, the remission rate of the patients with one-stage debridement was 88.18%, the remission rate of the patients with one-stage debridement plus antibiotic-loaded PMMA bone cement exclusion was 88.24%, and the patients who had CS or CS/CP had a 100% remission rate. Treatment of severe patients with sepsis and pulmonary infection. 15 of our patients (5.80%) had coexisting pulmonary infections. For patients with pulmonary infection, the precise diagnosis should be made first to avoid a missed diagnosis or a misdiagnosis. In addition to surgical treatment of local infections of the limbs, systemic intravenous therapy should be combined with appropriate antibiotics. In this subset of patients, we found that oxacillin was very effective unlike other antibiotics. All patients were successfully treated, and the lung infection was cured,such as case 1( Figure 3 ). The total Financial burden for the hospitalized patients with hematogenous osteomyelitis was 8,832,910 RMB. The median total cost for the hospitalized patients with hematogenous osteomyelitis was 25,754 RMB (11,502 RMB, 47,661 RMB). Among the main costs of the patients with hematogenous osteomyelitis, pharmaceutical costs accounted for the largest proportion (36.17%), followed by material costs (24.06%), anesthesia and surgery costs (17.47%), diagnosis costs (16.10%), comprehensive care costs (5.02%) and blood product costs (1.17%)( Table 7 ).

staphylococcus aureus, calcium sulfate/calcium phosphate bone cement, epidemiological, financial burden, hematogenous osteomyelitis

PMC6098914_01

Male

This patient is a 14-year-old male, who felt a popping sensation and significant right knee pain while jumping and colliding with another player during a basketball game the previous day. Following the injury, he was evaluated in an outside emergency department, where anterior, posterior, and lateral radiographs obtained in the emergency department demonstrated a tibial fracture consisting of two primary components (Figure 1). He was placed in a cast and sought a second opinion regarding findings and management. Upon presentation to the clinic the following day, he reported mild pain (3/10) and noted no normal function of his leg. A physical exam was performed but was limited due to pain. Following the review of radiographic imaging, an MRI was performed, which demonstrated a type IIIB tibial tubercle avulsion fracture and complete tear of the patellar tendon from its distal attachment site, as well as a hematoma at the fracture site (Figure 2). After discussing the findings with the family, the patient was scheduled to undergo open reduction internal fixation of a type IIIB fracture and repair of the patellar tendon three days following the initial injury. An 8-centimeter anterior incision was made at the superior aspect of the tibial tubercle and extended distally. At the patellar tendon insertion site on the tibia, the tendon was noted to be completely avulsed from the bone cortex distally, while proximally, the tendon remained attached to the displaced tubercle. The tendon remained attached to the inferior pole of the patella. The anterior tibial plateau fragment was anatomically reduced using two fully threaded noncannulated screws (Arthrex, Naples, FL), while the tibial tubercle fragment was reduced via bicortical fixation with a 50 mm fully threaded 3.5 mm cortical screw (Arthrex, Naples, FL). The distal patellar tendon was completely avulsed through two-thirds of its length. To restore the native footprint of the patellar tendon, a 4.5 mm PEEK (polyetheretherketone) corkscrew anchor (Arthrex, Naples, FL) was placed slightly lateral to the anatomic insertion site to avoid a stress riser on the anterior tibial cortex. The anatomic repair of the patellar tendon was completed with two mattress sutures and tied. In addition to the avulsion of the patellar tendon and periosteum, it was noted that fascial tissue with tibialis anterior muscle belly avulsed through the injury site causing subacute extensive bleeding within the anterolateral compartments (Figure 3). This scenario raised concern for impending compartment syndrome, and an anterolateral compartment release was planned. Three 3-centimeter incisions were made along the anterolateral aspect of the leg. The first was located 3 centimeters distal to the neck of the fibula, the second was located 10 centimeters above the distal fibula tip, and the third was located at the midpoint between the two. Under endoscopic visualization, the intramuscular septum was identified and Metzenbaum scissors were used to cut through the fascial compartment beginning in the anterior compartment and extending proximally then distally to the midtibia (Figure 4). The fascial incision was extended posteriorly into the peroneal compartment and then was extended proximally and distally to the midtibia. These steps were repeated for the midpoint and distal incision sites. Distally, the course of the superficial perineal nerve was identified and the nerve itself was protected during the distal release of the anterior compartment. It was believed that the impending compartment syndrome occurred due to damage to the surrounding bony and muscular tissue. A medium Hemovac drain was placed along the length of the lateral compartment, exiting in the posterolateral proximal leg. The patient was placed in a hinged knee brace which was locked in extension. He was discharged home later that day. On postoperative day number two, the patient's Hemovac drain was removed by a family member. The patient was seen 1 week postoperatively and noted moderate pain (6/10) and 0% normal function. On physical examination, incisional sites were clean, dry, and intact and a small fracture blister was noted on the posterior aspect of the knee:which was cleaned and redressed. Radiographic imaging revealed well-positioned screws, no evidence of new fractures or foreign bodies, and early evidence of callus formation. Two and a half weeks after surgery, the patient presented to the clinic for evaluation. He reported that he had no pain (0/10) and had 5% of his normal function at this time. On physical examination, he noted no tenderness to palpation of the knee joint, and he had 40 degrees of knee flexion. Anterior-posterior and lateral X-rays were taken which showed evidence of callus formation in the bone (Figure 5). At this time, it was recommended that the patient begin gentle active range of motion exercises with extension and light flexion. He was also encouraged to become full weight-bearing with the brace until its removal two months postoperatively. Five months postoperatively, the patient reported no pain (0/10) and possessed 95% of his normal function at this time. On physical examination, he was nontender to palpation along the joint line. There was no laxity with varus or valgus stress. He demonstrated 5/5 quadriceps strength with no evidence of an extensor lag. He had an active range of motion from 0 to 130 degrees of flexion, and there was no lag with straight leg raise. Repeat anterior-posterior and lateral X-rays demonstrated a well-reduced tibial tubercle fracture as well as well-positioned and nondisplaced hardware (Figure 6).

PMC9193368_01

Male

An 84-year-old Indian gentleman presented with a 1-month history of right eye pain, redness and photophobia. Four months earlier, he was diagnosed with stage 3 gastric adenocarcinoma (CPS <1; HER2 IHC 2+, FISH negative, pMMR). He had progressive gastric nodal spread despite having completed two cycles of Tegafur/Gimeracil/Oteracil (TS-1) adjuvant chemotherapy regimen 2 months prior. As he was not fit for surgery in view of his risks of receiving general anesthesia, a decision was made for him to receive treatment only with a palliative intent. His symptoms of right eye redness and ocular discomfort started ~1 month after completing his chemotherapy. On presentation, his best corrected visual acuity (BCVA) was 6/18 in the right eye. Slit lamp examination revealed mild conjunctival injection with two discrete areas of severe peripheral corneal melt spanning two clock hours nasally and two clock hours temporally with 60% thinning. There was an associated overlying epithelial defect, with Descemet membrane folds, and the presence of anterior chamber cells (grade 2). There was no scleritis (Figures 1A,B). Left eye and posterior segmental examination of both eyes were unremarkable. Extensive autoimmune and infective work up, including a full blood count, tuberculosis and syphilis screen, and an autoimmune serum panel (antinuclear antibody, anti-double-stranded DNA antibody, antinuclear antibody profile, ANCA-EIA profile) all returned negative. Due to progressive severe corneal thinning, the patient was then started on IV Methylprednisolone 500 mg/OM for 3 consecutive days, as well as topical steroids of Prednisolone Acetate 1% (Pred Forte, Allergan, Irvine Ca) hourly, Levofloxacin 0.5% (Cravit , Santen, Osaka, Japan) 3 hourly, oral Ciprofloxacin 500 mg twice daily, and oral Doxycycline 100 mg once daily. Over the course of 1 week, there was clinical improvement and thus his treatment was changed to oral Prednisolone 1 mg/kg that was tapered by 10 mg every 3 days. By day 9 of treatment, the area of corneal thinning had epithelized and there was no further stromal melting (Figures 1C,D).

corneal, inflammation, malignancy, paraneoplastic, peripheral ulcerative keratitis

PMC9817160_01

Male

A 46-year-old man underwent resection of the right kidney in February 2020 due to a cystic variant of renal cell carcinoma complicated with a urinary fistula. Three weeks post-surgery, the patient developed a UTI. A standard microbiological laboratory test identified Enterococcus faecalis and Pseudomonas spp. In urine and, based on disk-diffusion AST, meropenem and clindamycin were prescribed. The response was insufficient and the bacteria persisted for the next two weeks, which prompted treatment with meropenem and levofloxacin (Fig. 1). Nevertheless, the patient was still infected with E. faecalis and reinfected with Achromobacter xylosoxidans. In June 2020, E. faecalis and reinfection with Pseudomonas aeruginosa were confirmed, but due to the absence of clinical symptoms the patient was left untreated. Within a month, clinical symptoms of UTI appeared and P. aeruginosa was detected in urine; hence, the patient was administered fosfomycin, as suggested by conventional AST. However, the infection recurred and in August 2020 the patient was administered another course of fosfomycin due to persistence of P. aeruginosa along with reinfection with Escherichia coli. In February 2021, P. aeruginosa and reinfection with Klebsiella pneumoniae were identified, prompting treatment with a course of cefepime according to AST data. By April 2021, recurrence of P. aeruginosa and E. faecalis was noted and the patient was treated with ceftriaxone. During the next months, P. aeruginosa was detected in urine and, based on AST results, levofloxacin and cefepime were administered, but the infection recurred every time. Finally, in March 2022, the treating doctor prescribed a therapy based on antibiotic identification with AtbFinder. Whereas routine AST identified only P. aeruginosa, AtbFinder detected P. aeruginosa, Staphylococcus aureus, A. xylosoxidans, and K. pneumoniae in the same urine sample. Accordingly, cefepime, moxifloxacin, cefepime + amikacin, meropenem + amikacin, and piperacillin/tazobactam + tobramycin were identified as effective by microbroth dilution, but ineffective by AtbFinder (Table 1). Instead, the latter identified ceftriaxone + amikacin, levofloxacin + azithromycin, and piperacillin/tazobactam + levofloxacin as effective (Fig. 2). The patient was eventually treated with a combination of levofloxacin and azithromycin, which resulted in the rapid disappearance of clinical symptoms. At the check-up visit in May 2022, A. xylosoxidans was detected; however, no clinical data supported ongoing UTI. AtbFinder identified colistin, cefepime + levofloxacin, and tigecycline as effective, and the patient was treated with colistin for 5 days. At the next follow-up visits in August and October 2022, no bacterial growth in urine was detected using either conventional AST or AtbFinder.

antibiotics, atbfinder, drug resistant, susceptibility testing, urinary tract infection

PMC5640879_01

Female

A 30-year-old, previously healthy female, was first admitted to a local hospital on June 24, 2013 with main complaints of progressive headache, nausea, vomiting, and blurred vision which had persisted for 2 months. On admission, she was afebrile and general physical examination revealed no abnormalities. Her neurological abnormalities included bilateral papilledema, vision impairment, and signs of meningeal irritation. No motor or sensory deficits were seen. Blood tests of routine, biochemistry, coagulation, thyroid function, and various immunological parameters were all in the normal range. Blood antibodies for HIV, syphilis, and tuberculosis were negative. Initial brain MRI revealed a dilated left Sylvian fissure and an abnormal signal on the medial-dorsal side of the left thalamus (Figure 1A). Diffuse enhancement was noticed in the meninges, the left thalamus adjacent ventricular ependyma, the cerebellar tentorium, and the quadrigeminal cistern, whereas no enhancement was identified in the parenchyma (Figures 1B,C). Cerebrospinal fluid (CSF) analysis in the 3-series lumbar punctures revealed opening pressures higher than 400 mmH2O (reference range 80-180 mmH2O), with protein 2.59-5.01 g/L (reference range 0.15-0.45 g/L), glucose 2.20-2.79 mmol/L (reference range 2.5-4.5 mmol/L), chloride 121.1-126.3 mmol/L (reference range 120-130 mmol/L), and WBC 3-6/mL (reference range 0-5/mL) with 80-85% of lymphocytes. Negative results were reported in the following CSF etiological investigations: polymerase chain reaction for tuberculosis, bacteria and fungi cultures, India Ink stain for Cryptococcus, and IgG and IgM antibodies targeting various viruses and parasites. CSF cytology studies did not reveal neoplasm and chest CT and abdomen CT scans did not indicate any abnormality. Tuberculous meningitis was suspected and treated with isoniazid, rifampicin, ethambutol, and pyrazinamide. Meanwhile, brain ventricular puncture and drainage were performed and this dramatically attenuated the headache symptoms. The extraventricular drainage device was removed after 2 weeks and shortly thereafter the patient suffered from generalized tonic-clonic seizures. Once the seizures were controlled, a ventricular-peritoneal shunt was placed, resulting in an improvement of the patient's symptoms. Anti-tubercular therapy was given for 2 months, and then it was discontinued once it proved to be ineffective. In January 2014, the patient's severe headaches returned and her CSF pressure reached 500 mmH2O. Apart from a further decrease of glucose (1.88 mmol/L), her CSF analysis remained essentially unchanged. The brain MRI at this time revealed a round mass in the quadrigeminal cistern, multiple cyst signals in the Sylvian fissures, and the dilated cortical sulci in addition to the lesion in left thalamus. Overall contrast enhancement was present in the cerebral meninges, the cerebellar tentorium, the cyst walls, and the quadrigeminal cistern (Figures 2A,B). The ventricular-peritoneal shunt pressure was adjusted to 200 mmH2O and stereotactic biopsy of the left thalamus was performed. However, the infiltration by a few lymphocytes was the only observation. The patient's condition deteriorated as generalized seizures became more frequent. In April 2014, she was transferred to our hospital. Upon admission, abnormal neurological findings included confusion, slow light perception, limited abduction of both eyes, grade IV of muscle strength of the right arm, general hyperactive tendon reflexes in both legs, positive Babinski's sign on the right side, and positive meningeal signs. The third brain MRI, performed at this time, showed a non-contrasted, non-cystic lesion in the left paraventricular white matter and a contrasted cystic lesion in the left basal ganglia. All the previous changes were found to be more pronounced, including the cyst-like signals in the dilated cortical sulci, the mass in the quadrigeminal cistern, and the enlarged subarachnoid space, and general meningeal enhancement in the brain and upper segment of the cervical spinal cord (Figures 3A-C). Magnetic resonance spectroscopy (MRS) indicated a Cho/Cr wave ratio higher than 2.5 in the left thalamus and basal ganglia area (Figure 3D), and 1.0 in the right symmetric area that appeared normal on MRI (Figure 3E). Brain biopsy of the left temporal lobe was performed and spindle-shaped tumor cells were found to be spreading into the leptomeninges and subarachnoid space, which were strongly positive for glial fibrillary acidic protein (GFAP) and S100, partly positive for OLIG2 and P53, and negative for IDH1(R132H), ARTX, and NeuN (Figure 4). Ki-67 reactivity in tumor tissue was about 5%. According to 2016 World Health Organization (WHO), classification of tumors of the central nervous system, anaplastic astrocytoma, IDH-wildtype (WHO grade III) was confirmed. Combined with the extensive changes in brain MRI, PDLG was diagnosed. The patient refused treatment and was discharged from the hospital. She died 2 months later.

brain magnetic resonance imaging, dynamics, infiltration, parenchyma, primary leptomeningeal gliomatosis

PMC6136483_01

Male

A 17-year-old male professional motocross athlete with a history of left tibial spine avulsion fracture and resultant chronic knee flexion contracture presented to the emergency department (ED) status-post motocross injury with isolated left thigh pain. The patient had been wearing a hard-shell, hinged, knee brace measuring approximately 43 cm in length. He reported riding over a jump of approximately 10 feet when his left leg slipped off, pinning and hinging his leg over his knee brace. He was found to have a closed and neurovascularly intact transverse femoral shaft fracture without ecchymosis, skin changes, or open wounds. The deformity measured approximately 26 cm from the tibial tuberosity on clinical exam, and the fracture was 22 cm proximal to the center of the knee as measured on anterior-posterior (AP) radiograph (Figure 1). Per institutional protocol, thin-slice computed tomography (CT) was obtained to rule out femoral neck fracture, and this was negative for fracture. The patient was placed in Buck's traction and prepared for surgical intervention. Anterograde intramedullary nailing of the left femur with a femoral reconstruction nail was performed the next morning. The patient received routine perioperative antibiotic prophylaxis, unrestricted postoperative weightbearing, and one month of chemical deep vein thrombosis (DVT) prophylaxis. The patient had returned to full activity and competitive motocross at one-year follow-up.

PMC6136483_02

Male

A 17-year-old male professional motocross athlete with a history of pediatric left tibial shaft fractures (treated nonoperatively and complicated by painless varus malunion) presented to the ED after crashing his dirt bike. He had been wearing a hard-shell, hinged, knee brace measuring approximately 42 cm in length when he fell on his left side and hyperextended his left leg over the top of his knee brace. The patient complained of isolated left thigh pain. Evaluation of the patient revealed a closed, neurovascularly intact transverse femoral shaft fracture without ecchymosis, skin changes, or open wounds. The deformity was approximately 27.0 cm from the tibial tuberosity on clinical exam and measured 21.1 cm proximal to the center of the knee on AP radiograph (Figure 2). His baseline tibial deformity was unchanged. Again per institutional protocol, thin-slice CT pelvis was obtained to assess for associated femoral neck fracture, and this was negative. The patient was taken to the operating room (OR) the next morning and was treated with an anterograde femoral reconstruction nail with cephalomedullary screws. He received routine perioperative antibiotic prophylaxis, unrestricted postoperative weightbearing, and one month of chemical DVT prophylaxis. At one-year postoperative follow-up, the patient had regained full function and had returned to motocross at his preinjury level.

PMC3977029_01

Male

A 12-year old male with a severe TBI developed SADHD and significant problems with pragmatics of communication. Regulation of anger and sadness was unremarkable. Six months postinjury he was challenged more at school and fell behind his class. He experienced irritability, anger, and sadness and a diagnosis of an adjustment disorder with mixed emotional features was made. The clinician's formulation was that his affective instability was an indirect result of his TBI i.e. cognitive challenges led ultimately to school failure and his response included irritability and sadness. A 13-year old male with a severe TBI developed SADHD and significant challenges with pragmatics of communication. He was diagnosed with PC, affective instability subtype because regulation of anger and sadness was impaired in the hospital and persisted throughout the first year after the TBI. Six months postinjury he was challenged more at school and fell behind his class. He became even more irritable and sad but did not meet criteria for a major depression. The clinician's formulation was that his affective instability was a direct result of his TBI i.e. poor mood regulation and cognitive problems led to school failure and reduced his teacher's effectiveness in working with him.

brain imaging, novel psychiatric disorder, pediatric traumatic brain injury, review, risk factors, treatment

PMC9674528_01

Unknown

Measles outbreaks continue to be recorded in several districts, sometimes two weeks after the vaccination campaign in Niger. In 2019, in Niger the number of suspected cases was 2,568 with 431 confirmed cases. This number was significantly high compared to the 1,445 suspected cases and 397 positive cases recorded in 2018. This was after several actions had been undertaken including the establishment of case-by-case measles surveillance, the strengthening of the expanded routine vaccination program with the introduction of a catch-up dose of the measles vaccine in children under one-year-old, strengthening communication activities. It was necessary to conduct a database analysis to characterize the epidemiology of measles in Niger and improve the surveillance system.

measles, niger, database, surveillance

PMC4995537_01

Female

We report a case of chronic patellar tendon rupture in a 49 years old female patient who has been suffering from rheumatoid arthritis for over 20 years and was on a long-term therapy with corticosteroids and methotrexate. She came to our hospital complaining of her inability to extend the right knee which started suddenly a year and a half ago without any history of trauma. The reason behind the delayed presentation is that she had been managed in another hospital using different kinds of orthotics. Clinical examination showed a high riding patella along with a gap in the patellar tendon area. A magnetic resonance imaging (MRI) was done and it showed a complete rupture of the patellar tendon (Fig. 1). After seven months from the patient's presentation to our hospital, she underwent reconstruction of the patellar tendon using a massive BTB allograft. Prophylactic antibiotics were administered prior to surgery and the patient was put under general anesthesia with an appropriate dose of muscle relaxant. While the patient was in a supine position with a tourniquet applied and a bump placed beneath the ipsilateral thigh, a midline longitudinal incision extending beyond the superior pole of the patella and distal to the tibial tuberosity was made. The soft tissue was released to bring the retracted patella distally. The large bone block of the BTB allograft was fixed to the patella with two K-wires and a tension band in a similar technique to that used in the fixation of patellar fractures. After performing a tibial osteotomy to contain the distal bone block, the allograft was anchored to the tibia, more distal than usual, using two screws. The purpose of the distal placement was to utilize the graft which had a greater than ideal length while maintaining an optimal tension of the knee extensor mechanism. After closure, two views of plain radiographs were taken (Fig. 2). Early range of motion was allowed through a flexion-extension knee orthotic. Passive full extension and 30 of flexion were permitted. Partial weight bearing and active extension began three weeks after surgery. No complications were observed in the postoperative period. However, the two screws over the tibial tuberosity were removed after one year because of their prominence and x-ray images were taken afterwards showing an adequate union (Fig. 3). Three years after surgery, the patient had active and passive range of motion between -20 and 120 and was walking normally without any external support (Fig. 4, Fig. 5).

allograft, case report, late reconstruction, patellar tendon, rheumatoid arthritis

PMC8192201_01

Male

A 54-year-old gentleman with a history of well-controlled HIV established on Truvada and raltegravir, seizures, migraines, and previously treated syphilis presented to Croydon University Hospital with a 4-week history of progressive left leg weakness, bowel and bladder change, and a 1-week history of dysesthesia (Table 2). He denied any infective symptoms, weight loss, and personal or family history of tuberculosis (TB). He had no recent travel and reported no new sexual partners. Clinical examination revealed a normal cardiorespiratory examination. Neurologically, the patient had brisk reflexes in all limbs with reduced power (MRC 0/5) in the left leg combined with sensory dissociation starting from T5 in keeping with Brown-Sequard syndrome. Magnetic resonance imaging (MRI) of the spine undertaken at this time identified two peripherally enhancing cavitating lesions at T4-T5 with associated meningeal thickening and cord oedema. These images were felt indicative of CNS TB. Following this, anti-TB medication was started, and the patient was transferred to St. George's Hospital for further care. Cerebrospinal fluid (CSF) analysis undertaken revealed highly elevated protein (3.07 g/L) and white cell count (7 x 109/L). CSF cryptococcal antigen (CRAG), TB molecular testing (GeneXpert), microscopy and culture, and viral polymerase chain reaction (PCR) were all negative. Serial sputum acid-fast bacilli (AFB), peripheral blood cultures, and Q-interferon tests were negative. At this point, syphilis serological testing was undertaken; this suggested highly active acute infection (serum EIA positive and rapid plasma reagin (RPR) (1 in 64)). CSF serology showed positive Treponema pallidum particle agglutination (TPPA) 10240 and RPR 1 in 2 suggesting active disease. This raised the possibility of neurosyphilis with spinal syphilitic gumma. Due to no conclusive TB diagnosis, concurrent neurosyphilis treatment was initiated by way of 14-day high-dose benzylpenicillin therapy commencing on day 11 of presentation. Repeat MRI of the spine on days 12 and 22 of admission revealed incremental improvement in both spinal cord oedema and the size of the T4-T5 lesions (Figure 1). Following this, positron emission tomography-computed tomography (PET-CT) scan was performed on day 41 which showed no significant areas of increased uptake outside of the spine for potential biopsy. This improvement in the spinal disease was associated with progressive and marked improvements in his neurology, and by day 55, the patient could walk several lengths of parallel bars from being previously bedbound.