Significance of histopathological features in the diagnosis of Budd-Chiari syndrome on liver biopsies.

Background: Budd-Chiari syndrome (BCS) requires a constellation of clinical, imaging, and histological findings for diagnosis. Liver biopsy serves as a tool for confirming the diagnosis, even though the histological characteristics are not pathognomonic. Aims: To determine which constellation of morphologic findings could aid in establishing a diagnosis of BCS in clinically suspected cases. Materials and Methods: A 5-year retrospective observational study was conducted. The clinical, laboratory, and histological findings of liver biopsies in patients with a clinical diagnosis of BCS were studied. Cases were segregated into two groups on the basis of the number of histological features present. A scoring system was then devised to assess the efficacy of the histological findings in diagnosing BCS. Statistical Analysis Used: The continuous variables were compared using the Mann-Whitney U-test, and categorical variables were compared using the Fisher-exact test. Results: The common histopathological findings were the presence of red blood cells in the space of disse (100%), peri-portal fibrosis (97.1%), sinusoidal dilation (97.1%), portal inflammation (67.6%), centrilobular necrosis (61.8%) and pericellular/sinusoidal fibrosis (61.8%). Comparison between the two groups showed that centrilobular necrosis, lobular inflammation, portal inflammation, central vein fibrosis, and pericellular/sinusoidal fibrosis were significant parameters. No correlation was found between the clinical and laboratory parameters and the two groups. Conclusions: The liver biopsy features in BCS are often nonspecific, and no single feature in isolation is characteristic. A constellation of features (centrilobular necrosis, lobular inflammation, portal inflammation, central vein fibrosis, and pericellular/sinusoidal fibrosis), when present together, indicate the possibility of BCS.

Kidney transplantation in patients on anti-tubercular therapy: A single centre observational study.

BACKGROUND: Tuberculosis (TB) is a common infection in chronic kidney disease. The prolonged therapy of TB can delay kidney transplantation in patients on antitubercular therapy (ATT). METHODS: This was a retrospective single-center study to analyze the safety of kidney transplantation and its outcomes in patients undergoing transplantation while on the continuation phase of ATT. RESULTS: Between 2013 and 2022, 30 patients underwent kidney transplantation while on ATT. Median age was 38 years and 70% were males. Majority of the patients (86.7%) had extrapulmonary tuberculosis, most common site of involvement being tubercular lymphadenitis. 14/30 patients had microbiological/histopathological diagnosis of TB and the rest were diagnosed by ancillary tests. Patients were treated with 4 drug ATT (isoniazid, rifampicin, pyrazinamide, ethambutol) before transplantation for aminimum of 2 months. Post-transplantation fluoroquinolone-based non-rifamycin ATT was used (median duration 11 months). All patients completed therapy. At 2 years, there was 100% patient survival and 96.7% graft survival. Median eGFR at 6, 12, and 24 months post-transplantation was 71.9, 64.7, and 67 mL/min/1.73m2 , respectively. The percentage of patients suffering a biopsy proven acute rejection at 6, 12, and 24 months was 3.3%, 6.7%, and 6.7%. CONCLUSION: Kidney transplantation can be done in patients with TB who have a satisfactory response to the intensive phase of the ATT. The decision for transplantation while on the continuation phase of ATT should be individualized. In our experience, there is excellent patient and graft survival in these patients with a low risk of failure of ATT or relapse of TB.

An Intriguing Case of Amyloidosis Leading to PAGE Kidney in a Post Renal Transplant Recipient: A Case Report.

Amyloidosis is an infiltrative disease where amyloid fibrils get deposited in the organs like kidney, liver and spleen. Amyloid deposition in the kidneys classically meant deposition in the glomeruli and mesangium until 2008 when interstitial amyloid deposits were isolated and named as` Leukocyte cell-derived chemotaxin 2-associated amyloidosis. It is a progressive disease which clinically manifests as slowly progressive renal dysfunction and/or proteinuria. Our case 34 year old renal transplant recipient underwent graft biopsy post transplantation which revealed interstitial LECT-2 amyloid deposits. Unfortunately, he developed page kidney post biopsy which was managed conservatively with percutaneous drainage. Supplementary Information: The online version contains supplementary material available at 10.1007/s12291-022-01072-6.

Unilateral Multicystic Dysplastic Kidney Management: A National Survey.

Risks of contralateral kidney abnormalities and chronic kidney disease necessitate follow-up for unilateral multicystic dysplastic kidneys (MCDK). A nationwide survey of senior UK pediatricians was conducted. Of the 60 responses obtained, 62% routinely perform a dimercaptosuccinic acid scan to confirm diagnosis. Eight percent routinely perform a cystogram to investigate contralateral vesicoureteric reflux. Sixty-two percent would routinely measure renal function (frequency ranging from once only to "every 2 years"). Twenty-five percent recalled MCDK nephrectomy being performed within the previous 5 years. Respondents voiced concerns that national guidance may result in an overcautious approach but could balance consensus and safe variation, and offer families choice and reassurance. The mean estimated cost of follow-up from birth to 18 years ranged from £258 to £3854. Results demonstrate significant variation in management, highlighting the need for a clear pathway to decrease unwanted variability and to ensure those at high risk of renal sequelae are recognized early, without undue investigatory burden.

Pediatric Thyroid Lesions: Synergistic Role of Clinical and Cytological Features in Diagnosis.

INTRODUCTION: Thyroid lesions in childhood and adolescence are uncommon, and the risk of malignancy widely varies. They require careful evaluation and more aggressive diagnostic approach. The present study aimed to evaluate the frequency of various pediatric thyroid lesions in pediatric cases with thyroid nodules and ascertain the utility of clinical, laboratory, ultrasonography, and fine-needle aspiration cytology (FNAC) findings to discriminate between benign and malignant lesions. METHODS: A retrospective study where 95 consecutive cases of pediatric patients with thyroid nodules received over six years (January 2016-December 2021) were retrieved from the hospital information system. The differences in clinical, laboratory, ultrasonography, and cytological findings between benign and malignant lesions were analysed. Statistical analysis was performed using SPSS software (version 21.0). RESULTS: The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) was used to categorise the cases into: unsatisfactory (n=3), benign (n=66), intermediate (n=8) and suspicious/malignant (n=18). The specificity of cytopathology in diagnosing benign lesions (TBSRTC-II) was 90%, whereas sensitivity in diagnosing malignant lesions (TBSRTC-VI) was 100%. Colloid nodule (n=57) and papillary thyroid carcinoma (n=15) were the most common benign and malignant lesions encountered respectively. Malignant lesions more frequently showed the presence of palpable lymph nodes (p-value <0.001), microcalcifications (p-value 0.011) and intranodular vascularization (p-value <0.001). CONCLUSION: The diagnosis of pediatric thyroid lesions should be based on a multistep evaluation that includes clinical, laboratory, and radiographic modalities. Thyroid function tests and ultrasonography can help identify clinically unapparent thyroid nodules and provide detailed nodule characterization for suspected malignant lesions. FNAC is a simple, less-invasive, and cost-effective technique that can differentiate between benign and malignant thyroid lesions.

Case Reports on Black Fungus of the Gastrointestinal Tract: A New Complication in COVID-19 Patients.

Gastrointestinal mucormycosis is a rare disease with a significant mortality rate, even when promptly diagnosed and treated. An unusual complication was observed in India during the second wave of coronavirus disease 2019 (COVID-19). Two incidences of gastric mucormycosis were found. A 53-year-old male patient with a history of COVID-19 one month earlier came into the intensive care unit. After admission, the patient developed hematemesis, which was initially treated with blood transfusions and digital subtraction angiography embolization. Esophagogastroduodenoscopy (EGD) revealed a large ulcer with a clot in the stomach. During an exploratory laparotomy, the proximal stomach was necrotic. Histopathological examination confirmed mucormycosis. The patient was started on antifungals, but despite rigorous therapy, the patient died on the tenth postoperative day. Another patient, an 82-year-old male with a history of COVID-19, arrived with hematemesis two weeks earlier and was treated conservatively. EGD revealed a large white-based ulcer with abundant slough along the larger curvature of the body. Mucormycosis was verified by biopsy. He was treated with amphotericin B and isavuconazole. He was discharged after two weeks in a stable condition. Despite quick detection and aggressive treatment, the prognosis is poor. In the second case, prompt diagnosis and treatment saved the patient's life.

Invasive Micropapillary Urothelial Carcinoma: an Uncommon and Underreported Variant in Cystectomy Specimens.

Conventional urothelial carcinoma is the most common histological type of urinary bladder carcinoma. The latest edition of the WHO classification of tumours of the urothelial tract lays special emphasis on the ability of urothelial tumours to exhibit divergent differentiation with multiple histologic variants and a diverse genomic landscape. The presence of a micropapillary component (MPC) in urothelial carcinoma is associated with high-grade disease and poor response to intravesical chemotherapy. The present study aims to enumerate the clinicohistological features of urothelial carcinomas with micropapillary differentiation. Slides from 144 radical cystectomy specimens received over 6 years were reviewed independently by two pathologists. A predominant histological pattern along with co-existing pathology was noted. Of these, five cases were pure micropapillary carcinomas, four had conventional urothelial carcinoma with a MPC, one had a microscopic tumour at the mucosal surface, and two cases showed micropapillary histology in the lymph node metastasis, following transurethral resection of bladder tumour and Bacillus Calmette-Guerin therapy. The tumours with pure micropapillary carcinoma presented with a higher pathological stage and poor overall survival. Organ and lymph node metastasis was noted in five and eight cases, respectively, of which six showed a micropapillary pattern in the lymph nodes. Micropapillary urothelial carcinoma is a rare and aggressive variant of urothelial carcinoma with unique histologic features. This variant is often missed and underreported in biopsy and surgical resection specimens. Since the presence of MPC confers a poorer prognosis, the identification and reporting of this entity are important.

Photocatalytic Hydrogen Evolution by a De Novo Designed Metalloprotein that Undergoes Ni-Mediated Oligomerization Shift.

De novo metalloprotein design involves the construction of proteins guided by specific repeat patterns of polar and apolar residues, which, upon self-assembly, provide a suitable environment to bind metals and produce artificial metalloenzymes. While a wide range of functionalities have been realized in de novo designed metalloproteins, the functional repertoire of such constructs towards alternative energy-relevant catalysis is currently limited. Here we show the application of de novo approach to design a functional H2 evolving protein. The design involved the assembly of an amphiphilic peptide featuring cysteines at tandem a/d sites of each helix. Intriguingly, upon NiII addition, the oligomers shift from a major trimeric assembly to a mix of dimers and trimers. The metalloprotein produced H2 photocatalytically with a bell-shape pH dependence, having a maximum activity at pH 5.5. Transient absorption spectroscopy is used to determine the timescales of electron transfer as a function of pH. Selective outer sphere mutations are made to probe how the local environment tunes activity. A preferential enhancement of activity is observed via steric modulation above the NiII site, towards the N-termini, compared to below the NiII site towards the C-termini.

A Friend or a Foe? Bariatric Surgery in Chronic Kidney Disease: A Case Report.

There has been a parallel rise in the need for bariatric surgery as the prevalence of obesity has increased by leaps and bounds over the last 2 decades. Certain procedures like Roux-en-Y gastric bypass are associated with nephrolithiasis, hyperoxaluria, and, rarely, oxalate nephropathy. We report an interesting case of a patient who had relentless progression of his kidney disease post-bariatric surgery.

Meningeal Melanocytoma- A Clinicohistological Masquerader.

Meningeal melanocytoma is a rare benign tumor, most frequently located in the posterior fossa and spinal canal. Localized tumors present as leptomeningeal masses and range from well-differentiated melanocytomas to lesions of intermediate malignancy and overtly malignant melanomas. Spinal meningeal melanocytoma has a benign course and is amenable for gross total resection. The outcome is favorable following complete resection. Meningeal melanocytoma may occasionally be associated with histological benign leptomeningeal spread and aggressive clinical course in spite of the absence of malignant transformation. We report a case of intraspinal melanocytoma in a 57-year-old female, which clinically as well as radiologically mimicked other spinal lesions. The final diagnosis was confirmed on histopathology.

Poorly Differentiated Lung Cancer with Intracardiac Extension Causing Malignant Stroke in a Peritoneal Dialysis Patient: a Case Report.

Cardiac involvement occurs in an almost one quarter of all the patients with lung cancer. Lymphatogenous spread is a more common route of tumor dissemination than the hematogenous spread. It was a retrospective case report. We hereby report a case of myocardial involvement by non-small cell lung cancer leading to an uncommon presentation of a malignant stroke and death in a peritoneal dialysis patient.

Racemose neurocysticercosis simulating tuberculous meningitis.

We report a patient with racemose neurocysticercosis, highlighting the diagnostic and management issues. A 37-year-old male had headaches, fever, and seizures for 8 months. He had a positive tuberculin test, cerebrospinal fluid pleocytosis, and hydrocephalus and exudates on MRI. His symptoms rapidly resolved following antitubercular and prednisolone treatment. After 2 months, he was readmitted with headache and vomiting, and his brain MRI revealed communicating hydrocephalus with a cyst in the lateral ventricle and subarachnoid space, which was confirmed as neurocysticercosis on the third ventriculostomy. The patient was managed with dexamethasone and a ventriculoperitoneal shunt. This case highlights that meningitis symptoms, CSF pleocytosis, and positive tuberculin tests may not always suggest tubercular etiology.

The prevalence and clinical characteristics of anti-HMGCR (anti-3-hydroxy-3-methyl-glutaryl-coenzyme A reductase) antibodies in idiopathic inflammatory myopathy: an analysis from the MyoCite registry.

This study aimed to determine the prevalence and clinical characteristics of anti-HMGCR antibodies in idiopathic inflammatory myositis (IIM) at a tertiary care centre in northern India. Data (adult and children) were retrieved from the MyoCite dataset, identifying patients with polymyositis, dermatomyositis, and antibody-negative IIM whilst fulfilling the ACR/EULAR criteria. SLE, sarcoidosis, and systemic sclerosis were included for comparison as disease controls. The baseline clinical profile, laboratory tests, and muscle biopsies were retrieved and analysed. Descriptive statistics and non-parametric statistics were used for comparison. Among 128 IIM (112 adults, 16 children, M:F 1:2.8) of age 37 (24-47) years and 6 (3-17) months disease duration, 4 (3.6%) young adults tested positive for anti-HMGCR antibodies. All children and disease control tested negative for the antibody. Anti-HMGCR + IIM exhibited higher muscle enzymes [AST (367 vs 104 IU/L, p = 0.045), ALT (502 vs 78 IU/L, p = 0.004), and CPK (12,242 vs 699 IU/L, p = 0.001] except lactate dehydrogenase with less frequent systemic features such as fatigue than antibody-negative IIM. One young girl presented with a Limb-girdle muscular dystrophy (LGMD) with chronic pattern. None of the patients exhibited rashes, statin exposure, or cancer, though one had anti-Ro52 and mild disease. Our observations depict a younger population while affirming previous literature, including NM-like presentation, and chronic LGMD-like pattern of weakness in one case. Although a small number of children were included, ours is one of the few paediatric studies that evaluated HMGCR antibodies thus far. Further investigations in a larger Indian cohort are warranted to substantiate our findings.

Clinico-Histological Features of Thrombotic Microangiopathy in Renal Biopsies: A Retrospective Study.

OBJECTIVE: Thrombotic microangiopathy (TMA) is often first detected on a renal biopsy performed for renal manifestations. Apart from hemolytic uremic syndrome (HUS) and thrombotic thrombocytopenic purpura, there are various secondary conditions associated with TMA. This study analyzes the clinico-pathological spectrum, etiological factors and renal outcome of TMA diagnosed on renal biopsy. MATERIAL AND METHOD: A retrospective evaluation of renal biopsies for TMA over 5.5 years was performed. Clinical and laboratory data was collected from patient records. RESULTS: A total of 40 biopsies from 39 patients showed TMA comprising 33 native and 7 transplant biopsies. Malignant hypertension (n=13) was the most common etiology in native biopsies followed by postpartum TMA (n=7), atypical HUS (aHUS) (n=7), and lupus nephritis (n=6). TMA in transplant biopsies was due to acute rejection (n=4) and CNI toxicity (n=3). Serum creatinine was high in most patients (mean 5.6 + 2.5 mg/ dl). aHUS showed the highest mean LDH levels and the lowest average platelet counts. Renal biopsies in malignant hypertension and postpartum TMA showed isolated arterial changes while aHUS and lupus nephritis showed both glomerular and arterial involvement. Postpartum TMA and aHUS had poor renal outcome requiring renal replacement therapy. CONCLUSION: Most postpartum TMA and aHUS had systemic features of TMA while malignant hypertension and lupus nephritis showed 'isolated renal TMA'. This emphasizes the importance of careful evaluation of renal biopsies even in the absence of systemic features of TMA.

Carcinosarcoma of Gallbladder with Osteosarcomatous Differentiation - a Case Report with Review of Literature.

A 44-year-old female presented with dull upper abdominal pain. Contrast-enhanced computed tomography (CECT) of the abdomen revealed a well-distended gallbladder with multiple foci of minimally enhancing, intraluminal, soft tissue lesion, and hyperdensity on non-contrast scan measuring 4.3 × 3.5 cm in the fundus with few calculi embedded in it. There was no evidence of extraluminal extension. The patient underwent extended cholecystectomy with liver wedge resection. Histologically, the tumor showed both carcinomatous and sarcomatous components, with prominent osteosarcomatous differentiation. We report this unusual case and present a review of all cases of carcinosarcoma of the gallbladder with sarcomatous differentiation. Despite curative resection, CSGB prognosis remains poor, and thus, the authors recommend to focus their efforts to improve the surgical outcomes.

Fabry Disease: Report of Two Cases with Uncommon Presentation.

Fabry disease (FD) is a rare, lysosomal storage disorder characterized by multiorgan accumulation of predominantly globotriaosylceramide (GL3) and its metabolite. Resulting renal, cardiac, and cerebrovascular complications are crucial causes of morbidity and mortality in FD. Enzyme replacement therapy (ERT) shows promising outcomes for these patients, provided that therapy is initiated early. Thus, precise and early diagnosis of the disease is a pivotal factor determining the corollary of the disease. We report two cases of young adult males who presented to the nephrology department with proteinuria. A kidney biopsy was performed in both cases, which was suggestive of FD. The final conclusive diagnosis of FD was provided by electron microscopy.

Undifferentiated embryonal sarcoma of liver with macroaneurysms and arteriovenous shunt.

Undifferentiated embryonal sarcoma (UES) is an uncommon primary hepatic tumour of childhood. The mass usually shows paradoxical features of being cystic on CT and solid on ultrasound. These lesions are usually hypovascular. Very rarely they may present as hypervascular liver masses with macroaneurysms and arteriovenous (AV) shunt, with only less than six cases reported in literature. We report a case of an 11-year-old child who presented with progressive abdominal distention, and CT revealed a large exophytic hypervascular mass of liver with multiple macroaneurysms, pooling of contrast and a high-flow AV shunt. Histopathology, along with immunohistochemistry, revealed the mass to be UES. The child underwent neoadjuvant chemotherapy followed by successful surgery. The prognosis of this tumour depends on prompt diagnosis and early intervention. We present this case to highlight the atypical presentation of UES, which will encourage radiologists to keep this differential in relevant clinical settings.

De Novo Design of a Self-Assembled Artificial Copper Peptide that Activates and Reduces Peroxide.

Copper-containing metalloenzymes constitute a major class of proteins which catalyze a myriad of reactions in nature. Inspired by the structural and functional characteristics of this unique class of metalloenzymes, we report the conception, design, characterization, and functional studies of a de novo artificial copper peptide (ArCuP) within a trimeric self-assembled polypeptide scaffold that activates and reduces peroxide. Using a first principles approach, the ArCuP was designed to coordinate one Cu via three His residues introduced at an a site of the peptide scaffold. X-ray crystallographic, UV-vis and EPR data demonstrate that Cu binds via the Nε atoms of His forming a T2Cu environment. When reacted with hydrogen peroxide, the putative copper-hydroperoxo species is formed where a reductive priming step accelerates the rate of its formation and reduction. Mass spectrometry was used to identify specific residues undergoing oxidative modification, which showed His oxidation only in the reduced state. The redox behavior of the ArCuP was elucidated by protein film voltammetry. Detailed characterization of the electrocatalytic behavior of the ArCuP led us to determine the catalytic parameters (KM, kcat), which established the peroxidase activity of the ArCuP. Combined spectroscopic and electrochemical data showed a pH-dependence on the reactivity, which was optimum at pH 7.5.