Characteristics of Bilateral Adrenal Lesions: Experience from an Indian Tertiary Care Centre.

Introduction: The aetiologies in unilateral and bilateral adrenal lesions can be different with different clinical implications and management guidelines, the latter having aetiologies like hyperplasia, infections, infiltrative lesions and neoplasia. Bilateral tumours are more likely to have hereditary/syndromic associations. There is limited data on the clinical and pathological profile of bilateral adrenal lesions. Methods: This was a retrospective study where patients with bilateral adrenal lesions were selected from a total of 266 patients with adrenal lesions who presented to our institute between January 2016 and August 2022. The demographic, laboratory and imaging data were retrieved from the Hospital Information System and patient case files. Results: The study included 51 patients; the mean age at presentation was 51.15 years (range 14 to 82 years). Forty-eight patients (94.1%) were symptomatic at presentation with an average duration of symptoms being 10.68 months (range 10 days to 1 year). The most common presentation was adrenal insufficiency in 18 cases (38%), followed by fever in 17 cases (36%). The commonest aetiology, as revealed on histopathology, was histoplasmosis (n = 22, 43%), followed by pheochromocytoma (n = 11, 21.5%), metastases (n = 6, 11.7%), adrenal hyperplasia (n = 5, 9.8%), adrenocortical adenoma (n = 1, 1.9%), lymphoma (n = 3, 5.8%), neuroblastoma (n = 1, 1.9%), myelolipoma (n = 1, 1.9%) and tuberculosis (n = 1, 1.9%). Histoplasmosis and metastatic lesions were commonly seen in older people, and pheochromocytoma was associated with young age. 6/11 patients with a diagnosis of bilateral pheochromocytoma were associated with family history, genetic mutation and extra-adrenal involvement. Conclusion: The approach to bilateral adrenal lesions differs from that of unilateral lesions due to differences in aetiologies and the more significant role of genetics in some bilateral tumours. The age at presentation, presenting symptoms, lesion size and biochemical features help delineate varied underlying aetiologies.

Caught by Surprise - Microfilaria in Renal Biopsies.

Microfilarial parasites can obstruct the lymphatic tree giving rise to varying lymphatic and extra-lymphatic symptoms. Renal manifestations can range from asymptomatic proteinuria, chyluria, and nephrotic syndrome, to acute glomerulonephritis. The diagnosis of filariasis is usually made by the demonstration of the parasite in the peripheral blood smear, with or without eosinophilia. The renal involvement by this parasite has been sparsely reported in the literature. We hereby report five cases of filariasis detected on histopathological examination of renal biopsies, performed for other indications, along with a brief report of the additional histological findings. Three native and two graft biopsies were included. All our patients were male, with a mean age of 47 years (range 37 to 66 years). The serum creatinine ranged from 1.2 to 12.9 mg/dL. The mean 24-hour urinary protein was 3.6 gm/day. Peripheral blood eosinophilia was not recorded in any case, however, ESR was raised in all cases. Urine examination revealed varying proteinuria, with hematuria in two cases. Histological examination revealed microfilaria in all five biopsies, along with focal segmental glomerulosclerosis in two cases, combined cellular and humoral rejection, minimal change disease and acute tubular necrosis in one case each respectively. All patients were treated with diethylcarbamazine 6mg/kg/day or 12 days, in addition to the renal medications. Diagnosing the parasite is crucial as the patient is likely to benefit due to the timely treatment of the disease. Reporting this case series highlights an interesting finding in nephropathology.

Giant Myoid mammary hamartoma: A case report.

ABSTRACT: Mammary hamartoma are rare neoplasms of the breast. Myoid mammary hamartoma are a subtype comprising of prominent smooth muscle component along with normal breast tissue components including fibrous, adipose, and glandular tissue. We report the case of a 38-year-old lady who presented with a large 21 × 15 cm, firm, mobile lump in right breast, clinically mimicking as phyllodes tumor. The lesion was reported as BIRADS 4a on mammography. Fine needle aspiration cytology suggested benign breast disease. Wide local excision was performed. The excised lump was solid, gray-white with fatty yellowish areas. Histological features were of myoid mammary hamartoma. To the best of our knowledge, this is the largest myoid hamartoma reported till date. Fine needle aspiration, needle biopsy, and immunohistochemistry are of limited value as diagnostic modalities in these lesions. Complete surgical excision, proper identification, and follow-up is essential, as these lesions, more commonly those which are incompletely excised, can recur.

Discrimination of pediatric cryptogenic multifocal ulcerous stenosing enteritis from small bowel Crohn's disease and gastrointestinal tuberculosis: A retrospective study (with videos).

INTRODUCTION: Cryptogenic multifocal ulcerous stenosing enteritis (CMUSE) is a rare entity that mimics various inflammatory strictures of the small intestine. Pediatric literature is scarce. We analyzed the clinical, radiological, endoscopic and histopathological features of children with CMUSE that differentiate it from small bowel Crohn's disease (SBCD) and gastrointestinal tuberculosis (GITB). METHODS: CMUSE was diagnosed by the following criteria: (1) unexplained small bowel strictures with superficial ulcers, (2) chronic/relapsing ulcers of small bowel after resection, (3) no signs of systemic inflammation, (4) absence of other known etiologies of small bowel ulcers. SBCD and GITB were diagnosed based on standard criteria. The clinical features, laboratory parameters, radioimaging, endoscopy (including video capsule endoscopy [VCE], intra-operative endoscopy), histopathological features and treatment outcome were noted. RESULTS: Out of 48, CMUSE was diagnosed in 13 (27%) isolated small bowel and ileocecal strictures, while GITB and SBCD accounted for 41% and 21% cases, respectively. Common presentations were sub-acute obstruction (46%), obscure gastrointestinal bleeding (38%) and protein-losing enteropathy (38%). CMUSE patients had significantly longer disease duration compared to SBCD and GITB (p < 0.001). SBCD (90.0%) and GITB (85%) cases had elevated C-reactive protein (CRP), none with CMUSE had elevated CRP (p < 0.001). The disease was localized in jejunum (100%) and proximal ileum (56%) in CMUSE, ileocecal region (85%) in GITB, but evenly distributed in small intestine in SBCD. Endoscopy showed evenly placed, superficial, circumferential ulcers with strictures in CMUSE, deep linear ulcers in SBCD and circumferential ulcers in GITB. Upfront immunosuppression was given in four; three (75%) of them relapsed. Only surgery was done in three with one (25%) having relapse. Upfront surgery followed by immunosuppression was used in six, but all relapsed and two required repeat surgery. CONCLUSION: CMUSE is important but underdiagnosed in children. Lack of constitutional symptoms, normal inflammatory parameters and characteristic ulcers with strictures helped in differentiating CMUSE from GITB and SBCD.

Endobronchial Inflammatory Myofibroblastic Tumour Masquerading as a Ruptured Hydatid Cyst.

Inflammatory myofibroblastic tumours (IMTs) represent a rare group of neoplastic lesions characterized by a diverse clinical presentation. Endobronchial involvement is infrequently reported, and its manifestation mimicking the symptoms of a ruptured hydatid cyst adds an additional layer of complexity to the diagnostic challenge. This case report delves into an exceptional clinical scenario where an endobronchial IMT masqueraded as a ruptured hydatid cyst, initially confounding the diagnostic team. Through a detailed examination of the patient's clinical history, radiological imaging, bronchoscopy findings and subsequent histopathological analysis, we aim to contribute to the existing medical literature and shed light on the nuances encountered in accurately identifying and differentiating these two entities.

Prognostic significance of circulating microparticles in IgA nephropathy.

PURPOSE: Endothelial injury, involved in the pathogenesis of renal fibrosis, can generate microparticles (MPs). These are 0.1-1 µm membrane-bound vesicles shed from the damaged or activated cell surfaces. We analyzed the presence of circulating MPs and EnMPs in IgAN and correlated with markers of endothelial injury and disease activity. METHODS: The study included 30 IgAN (mean age 31.5 ± 9 years), 25 healthy controls and Lupus nephritis (n = 10) as disease controls. Circulating MPs were quantitated by Flow cytometry and EnMPs were analyzed using anti-CD31-FITC and anti-CD146-PE antibodies. Their levels were correlated with serum von Willebrand Factor, histological Oxford MEST-C score and renal outcome. A prospective validation group of 20 patients of biopsy-proven IgA nephropathy was also included. RESULTS: IgAN had significantly higher levels of MPs, EnMPs and vWF compared to controls. On multivariate analysis, plasma levels of total MPs, EnMPs and serum vWF correlated significantly with the presence of hypertension and E1 on histology. E1 and high MPs (> 130 counts/µl) were associated with shorter time to doubling of serum creatinine. MPs cutoff level of 130 counts/µl had a sensitivity of 75%, specificity of 93.3% and diagnostic accuracy of 89.5% for E1 in the validation cohort. CONCLUSION: Circulating MPs and EnMPs in IgAN correlate with E1 on histology and have a potential as non-invasive biomarkers to predict disease activity and renal outcome.

Role of percutaneous CT-guided biopsy in the characterisation of pleural diseases.

Background: Computed tomography (CT)-guided biopsy is emerging as a preferred and safe method for obtaining tissue samples in pleural diseases. Objective: This study aimed to evaluate the diagnostic yield and safety of percutaneous CT-guided biopsy in pleural diseases and to find CT findings predictive of malignant neoplastic pleural disease. Material and Methods: This retrospective study included 77 patients with pleural disease who underwent CT-guided pleural biopsies from July 2013 to May 2020. All procedures were performed with a coaxial semi-automatic biopsy device. Histopathology was performed in all cases, and additional tests such as immunohistochemistry (IHC) or microbiological analysis were carried out depending on clinical suspicion. The correlation of CT findings with final diagnosis was performed by Chi-square, Fisher's exact test and logistic regression analysis. Results: The overall technical success rate of CT-guided pleural biopsy was 100% with a diagnostic yield of 96.1%. No major complication was encountered, with minor complications encountered in the form of minimal pneumothorax and chest pain. Malignant pleural conditions constituted the largest group including metastatic adenocarcinoma as the most common (31.2%), followed by metastatic squamous cell carcinoma and mesothelioma. Tubercular pleural involvement was the second most common category (16.9%). The cartridge-based nucleic acid amplification test (CB-NAAT) assay had 90% sensitivity on pleural tissue in tubercular cases. CT features predictive of malignancy were irregular and nodular pleural thickening, mediastinal and diaphragmatic pleural involvement and mediastinal/chest wall invasion. There was a good correlation between higher pleural thicknesses with malignant outcome. Conclusion: Percutaneous CT-guided biopsy is a safe method for obtaining pleural tissue samples with high diagnostic yield. CT findings provide clues, which favour malignant pleural involvement.

Cost-Efficacy Analysis of Use of Frozen Section Histology for Margin Assessment During Breast Conservation Surgery in Breast Cancer Patients.

BACKGROUND: Margin assessment is an essential component of breast conservation surgery (BCS). Re-excision of infiltrated margin(s) detected on paraffin section histology (PSH) needs reoperation, adding time, inconvenience and cost. Intra-operative assessment of margins using frozen section histology (IFSH) can potentially obviate need for re-operation, thus facilitating one-step oncologically complete BCS. METHODS: IFSH and PSH reports of consecutive patients undergoing BCS (2010-2020) were reviewed. Accuracy and cost-efficacy of IFSH were assessed, considering PSH as gold standard. Cost of achieving oncologically complete BCS in whole cohort with IFSH (Scenario-A) was calculated and compared using appropriate statistical tests, with hospital costs for the cohort in a hypothetical Scenario-B, where IFSH was presumed not to have been used and all patients with infiltrated margin(s) on PSH would have been re-operated. RESULTS: Of the 367 patients screened, 39 were excluded due to incomplete IFSH data. Of 328 patients analyzed, 59 (18%) had one or more margins were reported infiltrated on IFSH, managed by re-excision or mastectomy in the same sitting, thus avoiding a reoperation. Additional 8 (2.4%) had involved margins on PSH (False negative IFSH). Significantly higher number of reoperations (p < 0.001) would have been needed in scenario-B. Average cost of the first operation with use of IFSH was Indian Rupees (INR) 25791 which included INR660 as IFSH cost. The average cost of reoperation was INR23724 which could be avoided in 59 (18%) by use of IFSH. The average cost per patient to achieve oncologically complete surgery in scenario A utilizing IFSH was significantly lower (p = 0.001) by INR3101 (11.7%), c.w. that in scenario B. Significant cost-saving with IFSH was maintained in cost-efficacy analysis undertaken with various higher and lower costs assumptions. CONCLUSIONS: Use of IFSH facilitates one-step oncologically complete BCS in majority of patients and results in considerable cost saving, resulting in avoidance of reoperations, besides preventing patient anxiety and delay in adjuvant treatment. TRIAL REGISTRATION: Clinical Trials Registry-India (CTRI/2021/08/035896).

Lower Circulating Cytotoxic T-Cell Frequency and Higher Intragraft Granzyme-B Expression Are Associated with Inflammatory Interstitial Fibrosis and Tubular Atrophy in Renal Allograft Recipients.

Background and Objectives: Inflammatory interstitial fibrosis and tubular atrophy (i-IFTA) is an inflammation in the area of tubular atrophy and fibrosis. i-IFTA is poorly associated with graft outcome and associated with infiltration of inflammatory mononuclear cells. A cytotoxic T cell is a granzyme B+CD8+CD3+ T cell, mainly secret granzyme B. Granzyme B is a serine protease that may mediate allograft injury and inflammatory interstitial fibrosis and tubular atrophy (i-IFTA). However, there is no report identifying the association of granzyme B with i-IFTA after a long post-transplant interval. Material and Methods: In this study, we have measured the cytotoxic T-cell frequency with flow cytometry, serum and PBMCs culture supernatants granzyme-B levels with ELISA and intragraft granzyme-B mRNA transcript expression with the RT-PCR in RTRs in 30 patients with biopsy-proven i-IFTA and 10 patients with stable graft function. Result: The frequency of cytotoxic T cells (CD3+CD8+ granzyme B+) in SGF vs. i-IFTA was (27.96 ± 4.86 vs. 23.19 ± 3.85%, p = 0.011), the serum granzyme-B level was (100.82 ± 22.41 vs. 130.32 ± 46.60, p = 0.038 pg/mL) and the intragraft granzyme-B mRNA transcript expression was (1.01 ± 0.048 vs. 2.10 ± 1.02, p < 0.001 fold). The frequency of CD3+ T cells in SGF vs. i-IFTA was (66.08 ± 6.8 vs. 65.18 ± 9.35%; p = 0.68) and that of CD3+CD8+ T cells was (37.29 ± 4.11 vs. 34.68 ± 5.43%; p = 0.28), which were similar between the 2 groups. CTLc frequency was negatively correlated with urine proteinuria (r = -0.51, p < 0.001), serum creatinine (r = -0.28, p = 0.007) and eGFR (r = -0.28, p = 0.037). Similarly, the PBMC culture supernatants granzyme-B level was negatively correlated with urine proteinuria (r = -0.37, p < 0.001) and serum creatinine (r = -0.31, p = 0.002), while the serum granzyme-B level (r = 0.343, p = 0.001) and intragraft granzyme-B mRNA transcript expression (r = 0.38, p < 0.001) were positively correlated with proteinuria. Conclusions: A decrease in the CTLc frequency in circulation and an increased serum granzyme-B level and intragraft granzyme-B mRNA expression shows that cytotoxic T cells may mediate the allograft injury in RTRs with i-IFTA by releasing granzyme B in serum and intragraft tissue.

Clinicopathologic characteristics and outcomes of late onset lupus nephritis: a single centre experience.

Systemic Lupus Erythematosus (SLE) occurs in the reproductive age group. Renal involvement occurs less frequently in late-onset SLE than in reproductive-age SLE patients. Here, we aimed to study the clinical, serological and histopathological characteristics of late-onset lupus nephritis (LN). Late-onset LN was defined as disease onset after 47 years of age, corresponding to the average menopausal age. Records of biopsy proven late-onset lupus nephritis patients diagnosed between June 2000 and June 2020 were reviewed. Late-onset LN constituted 53 of 4420 patients (1.2%) biopsied during the study period. Females represented 90.65% of the cohort. Mean age of the cohort was 49.5 ± 7.05 years at the time of SLE diagnosis while its renal presentation was delayed by median duration of 10 months (IQR 3-48 months). Renal failure was present in 28 patients (52.8%) with acute kidney injury (AKI) (28.3%, n = 15) as the most common presentation. On histopathological analysis, class IV was observed in 23 patients (43.5%), crescents were observed in one-third cases and lupus vasculopathy in 4 patients (7.5%). All patients received steroids. Majority of patients (43.3%; n = 23) received Euro lupus protocol for induction. On median follow up duration of 82 months, renal flares were noted in 9 patients (17%) and 8 patients (15.1%) became dialysis dependent. Among 11 patients (21%) with infectious complications, 7 patients (13.2%) suffered from tuberculosis. Infections caused three-fourth of the deaths. Late-onset lupus nephritis is rare and presents as renal failure in majority. Renal biopsy affects the clinical decision of judicious use of immunosuppression which is imperative due to high rate of infections in this cohort.

Pediatric Glomerular Diseases in North India-Epidemiology and Clinicopathologic Correlation.

Background: Glomerular diseases vary with age, and it is important to investigate the spectrum of glomerular diseases in pediatric patients to help in a more precise clinical diagnosis and optimize the management of patients. We aimed to study the clinicopathologic pattern of pediatric glomerular diseases in North India. Methods: This is a 5-year retrospective, single-center cohort study. The database was searched to identify all pediatric patients with glomerular diseases in their native kidney biopsies. Results: About 2890 native renal biopsies were studied, of which 409 were pediatric glomerular diseases. The median age was 15 years with a male preponderance. Nephrotic syndrome was the most common presentation (60.8%), followed by non-nephrotic proteinuria with hematuria (18.5%), rapidly proliferative glomerulonephritis (7%), isolated hematuria (5.3%), acute nephritic syndrome (3.4%), non-nephrotic proteinuria (1.9%), and advanced renal failure (0.7%). Minimal change disease (MCD) was the most common histological diagnosis, followed by focal segmental glomerulosclerosis (17.4%), IgA nephropathy (IgAN; 10%), membranous nephropathy (6.6%), lupus nephritis (5.9%), crescentic glomerulonephritis (2.9%), and C3 glomerulopathy (2.9%). Diffuse proliferative glomerulonephritis (DPGN) was the most common histological diagnosis in patients with hematuria and non-nephrotic as well as nephrotic range proteinuria. The most common histological diagnoses for isolated hematuria and acute nephritic syndrome were IgAN and postinfectious glomerulonephritis (PIGN), respectively. Conclusions: MCD and lupus nephritis are the most common pediatric primary and secondary histopathologic diagnoses, respectively. The adolescent-onset glomerular diseases have a higher frequency of IgAN, membranous nephropathy, and DPGN. PIGN is still an important differential in our pediatric patients presenting with acute nephritic syndrome.

Shear Wave Elastography: A Reliable Secondary Parameter for Diagnosing Biliary Atresia in Infants With Neonatal Cholestasis.

Objective In this study, we aimed to optimize various grayscale, Doppler, and elastography parameters and evaluate their diagnostic performance in the preoperative diagnosis of biliary atresia (BA). Materials and methods A total of 158 infants aged <6 months with neonatal cholestasis (NC) were enrolled in the study and sonography was performed after four hours of fasting. For comparison of elastography, 31 exclusively age-matched controls, not suffering from liver disease, were included separately. Triangular cord and gallbladder (GB) parameters were considered as primary parameters, while right hepatic artery (RHA) caliber, RHA-to-right portal vein (RPV) ratio, hepatic subcapsular flow (HSF), and shear wave elastography (SWE) were considered as secondary parameters. Diagnosis of infants with BA was confirmed on histopathology. Data were presented as mean ±standard deviation (SD) and frequency. Differences between groups were compared using the Chi-square test and the unpaired student t-test. Receiver operating characteristic (ROC) curve analysis was done for individual ultrasound/Doppler/SWE parameters to calculate the optimal cutoff value. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy were calculated for each parameter and their combinations. Results Of the primary parameters, GB contractility index (CI) and length showed the highest sensitivity and specificity respectively. A cutoff of 14 kPA was derived for SWE for the diagnosis of BA. Among secondary parameters, SWE had the best diagnostic performance, better than even the individual primary parameters. A combination of primary parameters with SWE in series showed the highest accuracy. Conclusion Among secondary parameters, elastography can prove to be highly useful. The highest accuracy in diagnosing BA can be obtained by combining primary parameters with SWE.

Utility of ultrasound Angio-PLUS imaging for detecting blood flow in breast masses and comparison with color Doppler for differentiating benign from malignant masses.

BACKGROUND: Tumor neo-angiogenesis plays an important role in the development and growth of breast cancers, but its detection by imaging is challenging. A novel microvascular imaging (MVI) technique, Angio-PLUS, promises to overcome the limitations of color Doppler (CD) in detecting low-velocity flow and small diameter vessels. PURPOSE: To determine the utility of the Angio-PLUS technique for detecting blood flow in breast masses and compare it with CD for differentiating benign from malignant masses. MATERIAL AND METHODS: A total of 79 consecutive women with breast masses were prospectively evaluated using CD and Angio-PLUS techniques, and biopsied as per BI-RADS recommendations. Vascular imaging scores were assigned using three factors (number, morphology, and distribution) and vascular patterns were divided into five groups: internal-dot-spot, external-dot-spot, marginal, radial, and mesh patterns. The independent samples t-test, Mann-Whitney U test, Wilcoxon signed rank test, or Fisher's exact test were used to compare the two groups as appropriate. Area under the receiver operating characteristic (ROC) curve (AUC) methods were used to assess diagnostic accuracy. RESULTS: Vascular scores were significantly higher on Angio-PLUS than CD (median=11, [IQR=9-13] vs. 5 [IQR=3-9], P < 0.001). Malignant masses had higher vascular scores than benign masses on Angio-PLUS (P < 0.001). AUC was 80% (95% CI=70.3-89.7; P < 0.001) for Angio-PLUS and 51.9% for CD. Using Angio-PLUS at a cutoff value of ≥9.5, sensitivity was 80% and specificity was 66.7%. Vascular pattern descriptors on AP showed good correlation with histopathological results (PPV mesh 95.5%, radial 96.9%, and NPV of marginal orientation 90.5%). CONCLUSION: Angio-PLUS was more sensitive in detecting vascularity and superior in differentiating benign from malignant masses compared to CD. Vascular pattern descriptors on Angio-PLUS were useful.

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.

Non-Diabetic Kidney Disease in Type 2 Diabetes Mellitus: A Changing Spectrum with Therapeutic Ascendancy.

BACKGROUND AND OBJECTIVES: Owing to changing epidemiology and therapeutic practices, a change in the spectrum of renal involvement in Type-2 diabetes mellitus (T2DM) has also been noted. The treatment of non-diabetic kidney disease (NDKD) differs from diabetic kidney disease (DKD) and the reversibility of NDKD in many cases to normal, prompts biopsy for rapid and accurate diagnosis. Data are scarce on kidney biopsy findings in T2DM. STUDY DESIGN & SETTING: In this observational study, we prospectively collected the data of kidney biopsies of patients aged ≥ 18 years with T2DM admitted between 1 August 2005 and 31 July 2022. The clinical, demographic and histopathological data were evaluated. The spectrum of kidney involvement in the form of DKD and/or NDKD was studied. The impact of these findings with the use of drugs retarding disease progression was also analyzed. RESULTS: A total of 5485 biopsies were performed during the study period and of these 538 patients had T2DM. The mean age of the study population was 56.9 ± 11.5 years and 81% were males. The mean duration of DM was 6.4 ± 6.1 years. Diabetic retinopathy (DR) was noted in 29.7%. The most common indication for biopsy was an acute rise in creatinine (147, 27.3%). Amongst the 538 diabetic patients who underwent biopsy, histological features only of DKD were noted in 166 patients (33%), NDKD alone in 262 (49%) and NDKD with DKD lesions in 110 (20%). On multivariate analysis, duration of DM less than 5 years, absence of CAD, absence of DR, oliguria at presentation, an acute rise in creatinine and low C3 were associated with NDKD. CONCLUSIONS: The prevalence of NDKD among diabetics and ATIN in particular might be on an increasing trend in the current era of changing T2DM epidemiological patterns. The use of anti-pro-teinuric agents was associated with lesser degrees of histopathological chronicity in T2DM.

Divergent manifestations and outcomes of diffuse crescentic immunoglobulin A nephropathy and pauci-immune crescentic glomerulonephritis on long-term.

BACKGROUND: Diffuse crescentic IgAN (CIgAN) is an uncommon phenotype of IgAN, which presents as rapidly progressive renal failure, similar to patients with pauci-immune crescentic glomerulonephritis(PCGN). There are limited data on outcomes comparisons between the two. METHODS: In this single-center, retrospective cohort study, we compared the clinical features, pathological presentation, and renal outcomes of 52 patients with CIgAN and 42 patients with renal-limited PCGN from January 2007 to December 2019. RESULTS: The CIgAN patients were younger (30.5 ± 13.8 years) than PCGN patients (46.1 ± 11.8 years) (P = 0.001). The CIgAN patients had a higher prevalence of hypertension (86.5% Vs. 41.3%, P = 0.001); and degree of proteinuria (4.2 ± 2.7 g/24 h Vs. 2.3 ± 1.16 g/24 h; P = 0.001) than PCGN patients. The chronicity in terms of global glomerulosclerosis, interstitial fibrosis, and tubular atrophy was higher in the CIgAN group than in the PCGN group. The remission rate with immunosuppression was significantly higher in the PCGN group than in the CIgAN group (P = 0.016). The end-stage renal disease (ESRD) or death within 1 year of diagnosis was significantly more in the CIgAN group (62.3% Vs. 39.1%) than PCGNgroup. For patients who were dialysis-dependent at presentation, the primary outcome of ESRD or death within one year was seen in 90.9% of patients of CIgAN and 44.1% in the PCGN group (P = 0.001). The long-term death non-censored renal survival is poor in the CIgAN group than in PCGN patients. However, patient survival is poor in PCGN patients. CONCLUSION: CIgAN is a different form of RPGN compared to PCGN and carries a poor prognosis despite similar immunosuppressive therapy in the long term.

Blood TGF-ß1 and miRNA-21-5p levels predict renal fibrosis and outcome in IgA nephropathy.

BACKGROUND: IgA nephropathy (IgAN), the most common primary glomerulonephritis, often presents as advanced renal failure with end-stage renal disease at diagnosis. Tubulointerstitial injury and fibrosis on histology are the most important predictors of renal outcome. A non-invasive biomarker is required for assessment of progression in IgA nephropathy. We investigated the utility of blood profibrotic molecules, TGF-ß1 and miRNA-21-5p (miR-21), to identify a non-invasive biomarker for renal fibrosis in IgAN. MATERIALS AND METHODS: The study included 30 IgAN (mean age 31.5 ± 9 years) at the time of initial diagnosis, 25 age-sex-matched healthy controls and 10 Lupus nephritis patients as disease controls. Serum TGF-ß1 was analyzed by enzyme-linked immunosorbent assay and plasma miR-21 by qRT-PCR, normalized with U6-snRNA. The levels were correlated with clinical features, laboratory parameters, histological Oxford MEST-C score and renal outcome. RESULTS: The serum TGF-ß1 and plasma miR-21 were significantly higher in patients with IgAN than in healthy controls. TGF-ß1 significantly correlated with serum creatinine, eGFR, Oxford T score and miR-21. High plasma miR-21 was significantly associated with T score and interstitial inflammation. On multivariate analysis, high levels of TGF-ß1 and miR-21 correlated with lower eGFR and T score, respectively. On a follow-up period of 21.5 months, high miR-21 expression at diagnosis was associated (p = 0.02) with a poor renal outcome having a shorter time to doubling of serum creatinine. CONCLUSION: High blood TGF-ß1 and miR-21 expression at diagnosis of IgAN show significant correlation with renal function and degree of chronic tubulointerstitial injury on histology.

Immunochemical characterisation of styrene maleic acid lipid particles prepared from Mycobacterium tuberculosis plasma membrane.

Membrane proteins of Mycobacterium tuberculosis (Mtb) can be targeted for the development of therapeutic and prophylactic interventions against tuberculosis. We have utilized the unique membrane-solubilising properties of the styrene maleic acid copolymer (SMA) to prepare and characterise 'styrene maleic acid lipid particles' from the native membrane of Mtb (MtM-SMALPs). When resolved by SDS-PAGE and visualised with coomassie blue, the molecular weights of Mtb membrane (MtM) proteins solubilised by SMA were mostly in the range of 40-70 kDa. When visualised by transmission electron microscopy, MtM-SMALPs appeared as nanoparticles of discrete shapes and sizes. The discoid nanoparticles exhibited a range of diameters of ~10-90 nm, with largest portion (~61%) ranging from 20-40 nm. MtM proteins of a molecular weight-range overlapping with that of MtM-SMALPs were also amenable to chemical cross-linking, revealing protein complex formation. Characterisation using monoclonal antibodies against seven MtM-associated antigens confirmed the incorporation of the inner membrane protein PRA, membrane-associated proteins PstS1, LpqH and Ag85, and the lipoglycan LAM into MtM-SMALPs. Conversely, the peripheral membrane proteins Acr and PspA were nearly completely excluded. Furthermore, although MtM showed an abundance of Con A-binding glycoproteins, MtM-SMALPs appeared devoid of these species. Immune responses of healthcare workers harbouring 'latent TB infection' provided additional insights. While MtM-SMALPs and MtM induced comparable levels of the cytokine IFN-γ, only MtM-SMALPs could induce the production of TNF-α. Antibodies present in the donor sera showed significantly higher binding to MtM than to MtM-SMALPs. These results have implications for the development of MtM-based immunoprophylaxis against tuberculosis.

Primary Renal Well-Differentiated Neuroendocrine Tumors: Analyis of Six Cases from a Tertiary Care Center in North India with Review of Literature.

Well-differentiated renal neuroendocrine tumors are rare tumors. As their biologic behavior is not fully known, there is a need to know more about these cases. We performed a retrospective chart review of all the cases diagnosed with renal neuroendocrine tumors from January 2016 to December 2020 (five years) in order to understand their clinical features, morphological characteristics and outcome. We included six cases with mean age of 46.2 years (4 males) in our study. All patients underwent radical nephrectomy. Histologically all showed tumor disposed in nests and trabeculae and majority of the tumors belonged to well-differentiated neuroendocrine tumor Grade 1 (WHO criteria of gastoroenteropancreatic neuroendocrine neoplasms). Lymph node metastasis was seen in two cases at the time of clinical presentation. All the tumors were diffusely positive for neuroendocrine tumor markers (synaptophysin, chromogranin, NSE, CD56). Follow-up data was available in all cases with an average follow-up of two years and neither has shown evidence of metastasis or relapse till last follow-up. Role of morphological patterns and immunohistochemical markers is highlighted with the importance of including Ki-67 index in grading them to better understand their outcome.