The Unusual Adverse Effects of Antituberculosis Therapy in Kidney Patients.

BACKGROUND: Chronic kidney disease (CKD) patients are at a high risk of tuberculosis (TB), with a relative risk of developing active TB of 10%-25%. Similarly, glomerular disease increases the risk of TB due to diminished glomerular filtration rate, proteinuria, and immunosuppression use. Further, the first-line anti-TB drugs are associated with acute kidney injury (AKI) even in patients with normal kidney functions. METHODS: We retrospectively identified 10 patients hospitalized with unusual adverse effects of antituberculosis therapy (ATT) from 2013 to 2022. RESULTS: We found three cases of AKI caused by rifampicin: acute interstitial nephritis, crescentic glomerulonephritis, and heme pigment-induced acute tubular necrosis. We observed rifampicin-induced accelerated hypertension and thrombocytopenia in two patients on maintenance hemodialysis. Isoniazid caused pancreatitis and cerebellitis in two CKD patients, respectively. In a CKD patient, we detected acute gout secondary to pyrazinamide-induced reduced uric acid excretion. We also observed cases of drug rash with eosinophilia and systemic symptoms and hypercalcemia due to immune reconstitution inflammatory syndrome in patients with glomerular disease on ATT. Immediate discontinuation of the offending drug, along with specific and supportive management, led to a recovery in all cases. CONCLUSION: The adverse effects of ATT may be unusually severe and varied in kidney patients due to decreased renal elimination. Early recognition of these adverse effects and timely discontinuation of the offending drug is essential to limit morbidity and mortality.

Salivary gland tumors: an audit from a tertiary care centre in Northern India.

Salivary gland tumors are relatively rare and can exhibit various clinical behaviors. The study aims to understand the natural history, pathology, diagnostic workup, and treatment strategies for these tumors to improve patient outcomes. The audit included patients with salivary gland tumors detected through radiology or cytology. Patients underwent surgery, with some receiving adjuvant treatment. Demographic information, treatment interventions, and survival outcomes were analyzed using SPSS software. A total 89 as malignant salivart gland tumours were audited Malignant tumors were predominantly found in the parotid gland, with fewer cases in the minor salivary gland and submandibular gland.The median age of presentation was 47 years, and the majority of patients were male. The study examined various pathological and clinical factors, including tumor stage, nodal status, and the presence of facial palsy. Surgical procedures and histological types of tumors were documented. Adverse histological features like positive margins, lymph node positivity, lympho-vascular invasion, extracapsular spread, and perineural invasion were noted. POSTOP RT was administered to high-risk patients. Most malignant salivary gland tumors were found in the parotid gland, while minor salivary gland tumors were underrepresented in the audit. Surgical practices were diverse. Radiotherapy protocols were relatively standardized. The study found that certain histological features, such as lymph node positivity, margin positivity, lympho-vascular invasion, perineural invasion, and extracapsular spread, were associated with adverse effects on DFS and OS. The findings suggest that specific histological features, including LVI and ECE have emerged as independent prognostic factors for DFS and OS.

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.

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.

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.

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.

A case of strongyloidiasis with aplastic anaemia: A common disease with an uncommon presentation.

Strongyloidiasis is an opportunistic infection caused by the nematode helminth Strongyloides stercoralis and transmitted mostly via soil. The disease is usually asymptomatic, limited, and long-standing. Herein, we report a case of strongyloidiasis in a patient who seemed to be immunocompetent despite his malnourished appearance. He was presented with pancytopenia and aplastic anaemia and well responded to albendazole therapy with complete resolution of symptoms within three months. We recommend, prior to beginning of immunosuppressive regimens, it may be prudent to examine all patients presenting with abdominal discomfort along with pancytopenia for a possible worm infestation. Bone marrow suppression induced by worm infestation is an extremely rare but potentially comorbid condition that can lead to pancytopenia and severe aplastic anaemia.

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.

Clinical characteristics of patients with diffuse alveolar hemorrhage diagnosed by cytological examination of 1000 bronchoalveolar lavage samples.

BACKGROUND AND AIM: Diffuse alveolar hemorrhage (DAH) is a life-threatening condition due to the extravasation of blood in the alveoli, resulting in hypoxemia and even acute respiratory distress syndrome. This study aimed to describe the clinico-radio-pathological profile of patients diagnosed with DAH and classify it into immune and nonimmune DAH. METHODS: This was a retrospective analytical study. Of a total of 1000 cases of bronchoalveolar lavage fluids (BALF) received for cytological examination, patients fulfilling the clinical, radiological, and laboratory details of cases satisfying the clinical and cytological criteria of DAH (n=47) were studied. RESULTS: The most common cause of immune DAH was ANCA-associated vasculitis (n=13, 27.6%), and that of nonimmune DAH was infections (n=10, 21.3%). Twenty-nine patients (61.7%) had hemoptysis. The most common radiological finding was ground-glass opacities (n=33, 70.2%). In univariate analysis, female sex, mean hemoglobin at admission, total leucocyte count (TLC), platelet count, and erythrocyte sedimentation rate (ESR) were significantly associated with immune-DAH. However, in multivariate analysis, female sex, higher TLC, high platelets, and high ESR were significantly associated with immune DAH. Patients were treated with corticosteroids (n=25, 46.3%), intravenous cyclophosphamide (n=12, 22.2%), plasma exchange (n=7, 13.0%), intravenous immunoglobulin (n=5, 9.3%) and rituximab (n=5, 9.3%). The overall mortality was 8.5% (n=4). CONCLUSIONS: DAH is a life-threatening syndrome that may be classified into immune and nonimmune DAH. Immune-DAH requires aggressive management, whereas nonimmune DAH cases respond best to conservative management.

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.