Validation of histopathological chronicity scores in native kidney biopsies using light microscopy and digital morphometry for predicting renal outcome.

Quantitative assessment of chronicity changes in native kidney biopsies offer valuable insights in to disease prognosis, despite the strength of qualitative information. Yet, standardization and reproducibility remain challenging. The present study aims to assess and compare the prognostic utility and reproducibility of two chronicity scoring systems based on light microscopy and whole slide imaging with morphometry and also to evaluate the prognostic utility of structural measurements: cortical non-sclerotic glomerular (NSG) density and NSG area/volume. We designed a retrospective longitudinal study involving 101 adult and paediatric patients who underwent native kidney biopsies. Chronicity scoring was performed using two semi-quantitative methods: Method 1 (method proposed in PMID: 28314581) and Method 2 (method proposed in PMID: 32516862), under light microscopy as well as on whole-slide scanned images, and assessed for prognostic utility. Kidney-Failure-Risk-Equation (KFRE) was employed in combination with chronicity-scoring-methods and assessed for predictive capability. Interobserver reproducibility for the two chronicity methods was studied among three renal pathologists. Structural measurements were performed on whole-slide- scanned-images. Both the chronicity scoring methods significantly predicted decline in estimated glomerular filtration rate (eGFR) and persistent need for renal replacement therapy in follow-up. Method 1 combined with KFRE, outperformed Method 2 in predicting renal survival. Method 2 however showed higher interobserver reproducibility. Combined KFRE plus histopathological scoring methods showed better predictive accuracy. The study validates the precision of chronicity scoring using whole slide scanned images. The morphometric structural measurements showed significant correlations with follow-up eGFR, thereby providing supplementary prognostic information.

Monocytes and Macrophages in Kidney Disease and Homeostasis.

The monocyte-macrophage lineage of inflammatory cells is characterized by significant morphologic and functional plasticity. Macrophages have broad M1 and M2 phenotype subgroups with distinctive functions and dual reno-toxic and reno-protective effects. Macrophages are a major contributor to injury in immune-complex-mediated, as well as pauci-immune, glomerulonephritis. Macrophages are also implicated in tubulointerstitial and vascular disease, though there have not been many human studies. Patrolling monocytes in the intravascular compartment have been reported in auto-immune injury in the renal parenchyma, manifesting as acute kidney injury. Insights into the pathogenetic roles of macrophages in renal disease suggest potentially novel therapeutic and prognostic biomarkers and targeted therapy. This review provides a concise overview of the macrophage-induced pathogenetic mechanism as a background for the latest findings about macrophages' roles in different renal compartments and common renal diseases.

Over expression of PI3K-AkT reduces apoptosis and increases prostate size in benign prostatic hyperplasia.

INTRODUCTION: Even though the role of the phosphatidylinositol 3-kinase (PI3K)/AKT pathways and apoptosis has been well established in prostate cancer, there are no studies regarding alteration in the gene expression of PI3K/AKT pathway and protein expression of apoptotic components and their association with prostate size in Benign prostatic hyperplasia (BPH). Hence the study was designed to analyze the expression pattern of PI3K/AKT and apoptotic components in patients with BPH. MATERIALS AND METHODS: A total of 27 BPH patients aged between 55 and 75 years were recruited in the study and prostatic tissues were obtained after transurethral resection of the prostate. Gene expression levels of PI3K and AKT were assessed by q-PCR. Apoptotic components like BcL-2, caspase-3, caspase-9, BAD, and p-BAD were analyzed by western blotting and immunohistochemistry. RESULTS: Gene expression of PI3K (p85-A) (p = .02), AKT1 (p < .01) and AKT2 (p < .01), and protein expression of BcL-2 (p < .01) and caspase-9 (p < .01) were significantly increased in BPH patients with larger prostate size compared to smaller prostate size. CONCLUSIONS: Overexpression of PI3K/AKT pathway and BcL-2 were associated with reduced apoptosis and increased prostate size in BPH.

Expression of the Folate Receptor Proteins FOLR1 and FOLR2 in Correlation With Clinicopathological Variables of Gastric Cancer.

INTRODUCTION: Gastric cancer (GC) remains a leading cause of cancer-related mortality worldwide, owing to its aggressive nature and poor prognosis. The role of folate receptors, particularly folate receptor 1 (FOLR1) and folate receptor 2 (FOLR2), in cancer has been increasingly recognized due to their overexpression in various malignancies including gastric cancer, and its potential implications in cancer progression, treatment resistance and as therapeutic targets. OBJECTIVE: To evaluate the expression patterns of FOLR1 and FOLR2 in GC patients' tissue and blood specimens and to correlate these patterns with clinicopathological variables. METHODS: A total of 58 gastric cancer patients were enrolled at the Regional Cancer Centre (RCC) from March 2017 to March 2020. Immunohistochemical analysis was performed to examine the expression of FOLR1 and FOLR2 in formalin-fixed paraffin-embedded (FFPE) tissue samples. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was performed to analyze FOLR1 and FOLR2 expression in blood samples. Statistical analyses were conducted using chi-square tests, independent T-tests, and Kaplan-Meier survival analysis. RESULTS: FOLR1 and FOLR2 were overexpressed in 82.76% and 70.69% of gastric cancer tissues, respectively. High expression levels of FOLR1 were significantly associated with the diffuse type of gastric cancer (p<0.005). qRT-PCR showed significant overexpression of FOLR1 in gastric cancer blood samples compared to control samples, with a median fold change of approximately 14.18 times. Conversely, FOLR2 was significantly underexpressed in gastric cancer samples, with a fold change of 0.30. However, no significant correlation was found between FOLR2 expression and the clinicopathological features. The overall survival analysis did not show a significant difference in survival rates based on the expression levels of FOLR1 and FOLR2. CONCLUSIONS: This study highlights the differential expression patterns of FOLR1 and FOLR2 in gastric cancer and underscores the complexity of their roles in cancer biology. While FOLR1 shows potential as a biomarker for gastric cancer due to its overexpression, further studies are needed to fully elucidate the therapeutic and prognostic implications of folate receptors in gastric cancer.

The Role of Circulating MicroRNAs in the Prediction of Response to Neoadjuvant Chemotherapy in Locally Advanced Breast Cancer in the Indian Population.

INTRODUCTION: MicroRNAs (miRNAs) are known to play an important role in cancer cell proliferation, susceptibility of cancer cells to chemotherapy, and patient survival. Identifying miRNAs that can predict response to chemotherapy in locally advanced breast cancer (LABC), the most common variant, can help to choose appropriate drug regimens to suit the epigenetic profile of individual patients. OBJECTIVE: To investigate the expression of the differentially expressed miRNAs identified by next-generation sequencing from a pilot study involving cases and controls, in peripheral blood mononuclear cells (PBMC) of patients with LABC during the course of neoadjuvant chemotherapy (NAC) and determine their role in response to chemotherapy. METHODS: This study included 30 newly diagnosed LABC patients. Peripheral blood from every participant was collected before the start of chemotherapy, at the end of the third cycle, and at the end of the seventh cycle of NAC. Based on the results of a pilot study in a similar population with suitable controls, four differentially expressed miRNAs namely miR-24-2, miR-192-5p, miR-3609, and miR-664b-3p were considered to be validated in this study. The expression of these four miRNAs was examined by qRT-PCR, and their association with response to chemotherapy was analyzed. RESULT:  A significant change in the expression of miR-192-5p was found in responders (p = 0.001) over a period of seven cycles and the difference between the expression of miR-24-2 from baseline to the seventh cycle of NAC was higher in responders while compared to the non-responders (p < 0.05). CONCLUSION: miR-192-5p and miR-24-2 were identified as predictive biomarkers for response to NAC in south Indian patients with LABC.

Flow Cytometric Assessment of CD26-Positive Leukemic Stem Cells: A Rapid and Valuable Tool in the Diagnosis and Follow-Up of Chronic Myeloid Leukemia.

Context Chronic myeloid leukemia (CML) is a clonal myeloproliferative neoplasm. Recent studies have suggested that CD26-positive leukemic stem cells (LSCs) circulating in peripheral blood are specific for CML. Objective This study was undertaken to determine the proportion of CD26-positive LSCs at diagnosis and its change during tyrosine kinase inhibitor therapy. Design This prospective study was conducted on 43 cases of CML at diagnosis. For flow cytometry, peripheral blood cells were stained with CD45, CD34, CD38, CD3, and CD26. A sequential gating strategy with CD45/SSC (side scatter), CD34/SSC, and CD34/CD38 was applied to identify CD45+/34+/38- populations, from which CD26-positive stem cells were identified and compared with controls. Data analysis was done with Kaluza software. Results All patients diagnosed with CML were detected with CD26-positive LSCs. The median percentage of CD26-positive CML LSCs was 0.02 with a range of 0.001 to 1.77. None of the control samples showed CD26 positivity. The percentage and absolute count of CD26-positive CML LSCs were reduced after six months of tyrosine kinase therapy in patients with complete hematological remission. Conclusion Flow cytometric analysis of circulating CD26-positive CML LSCs is a non-invasive, rapid, and useful tool in the diagnosis and follow-up of CML.

Pre-Transplant Cytokine Levels as Signatures of Microvascular Inflammation in Kidney Allograft Biopsies.

BACKGROUND:  The presence of microvascular inflammation (MVI) characterized by leukocyte margination in the glomeruli (glomerulitis, Banff score 'g') and peritubular capillaries (peritubular capillaritis, Banff score 'ptc') is a hallmark histological feature of antibody-mediated rejection (AMR), even in the absence of circumferential C4d positivity. In this study, we assessed the efficacy of pre-transplant plasma cytokines as an ancillary screening tool to identify MVI in kidney allograft indication biopsies to facilitate better graft survival. METHOD:  This single-center prospective analytical study comprises 38 kidney transplant recipients whose peripheral blood was collected before transplant and assessed for the plasma cytokine concentrations of FOXP3, IL-6, TGF beta, and IL-17 using enzyme-linked immunosorbent assays (ELISA). Histopathological assessment was done in post-transplant indication biopsies, and Banff scores of 'g+ ptc' were calculated to categorize recipients into three MVI groups. The correlational, regression, and ROC curve analyses were used to assess the association and predictive ability of the cytokines with respect to MVI. RESULTS:  In our study cohort, 27 recipients had MVI=0, five had MVI=1, and six had MVI≥2. A significant difference in plasma cytokines was observed between these groups, and we found a strong negative correlation of FOXP3 with MVI, whereas a strong positive correlation of IL-6, TGF beta, and IL-17 was recorded with MVI. We have also assessed the predictive ability of these cytokines, FOXP3, IL-6, TGF-beta, and IL-17, through the ROC curve, which showed an AUC of 0.70, 0.76, 0.84, and 0.72, respectively. CONCLUSION:  Our findings suggest that the pre-transplant levels of cytokines FOXP3, IL-6, TGF-beta, and IL-17 could be measured to identify recipients at risk of post-transplant MVI, which could further serve as an additional tool for effective management of the kidney allograft.

Vancomycin nephrotoxicity: A comprehensive clinico-pathological study.

INTRODUCTION: Vancomycin, a commonly prescribed antibiotic particularly in the setting of multi-drug resistant infections, is limited by its nephrotoxicity. Despite its common occurrence, much remains unknown on the clinicopathologic profile as well as the pathogenesis of vancomycin nephrotoxicity. Clinical studies included patients often with severe comorbidities and concomitant polypharmacy confounding the causal pathogenesis. Animal models cannot recapitulate this complex clinical situation. Kidney biopsy was not commonly performed. METHODS: To address this limitation, we studied 36 patients who had renal biopsies for acute kidney injury (AKI) for suspicion of vancomycin nephrotoxicity. Detailed renal biopsy evaluation, meticulous evaluation of clinical profiles, and up-to-date follow-up allowed for a diagnostic categorization of vancomycin nephrotoxicity (VNT) in 25 patients and absence of vancomycin nephrotoxicity (NO-VNT) in 11 patients. For careful comparison of these two groups, we proceeded to compile a clinicopathologic and morphologic profiles characteristic for each group. RESULTS: Patients with VNT had a characteristic clinical profile including a common clinical background, a high serum trough level of vancomycin, a rapidly developed and severe acute kidney injury, and a recovery of renal function often shortly after discontinuation of vancomycin. This clinical course was correlated with characteristic renal biopsy findings including acute tubulointerstitial nephritis of allergic type, frequent granulomatous inflammation, concomitant and pronounced acute tubular necrosis of nephrotoxic type, and vancomycin casts, in the absence of significant tubular atrophy and interstitial fibrosis. This clinico-pathologic profile was different from that of patients with NO-VNT, highlighting its role in the diagnosis, management and pathogenetic exploration of vancomycin nephrotoxicity. CONCLUSION: Vancomycin nephrotoxicity has a distinctive morphologic and clinical profile, which should facilitate diagnosis, guide treatment and prognostication, and confer pathogenetic insights.

Soluble Tumor Necrosis Factor Receptor 2: A Promising Predictive Biomarker for Renal Dysfunction in Membranous Glomerulonephritis.

Background and objective Membranous glomerulonephritis (MGN) is a common cause of adult nephrotic syndrome. Tumor necrosis factor-α (TNF-α) is a proinflammatory cytokine that signals by attaching to TNF receptors. TNF-α plays a pivotal role in the development and progression of different forms of glomerulonephritis. Several research findings suggest that TNF-α receptors (TNFR1 and TNFR2) are predictors of estimated glomerular filtration rate (eGFR) decline. In light of this, this study aimed to explore the relationship between TNFR2 and eGFR, as well as the predictive role of TNFR2 in eGFR decline in MGN. Methods A total of 50 consecutive patients with a diagnosis of primary MGN based on renal biopsies and clinical workups were included in the study. TNFR2 levels in serum, urine, and gene expression were evaluated at baseline and after three months of follow-up by using enzyme-linked immunosorbent assay (ELISA) kits for TNFR2 (KTE60215, Abbkine, Wuhan, China). Cox regression was employed to determine the predictive significance of TNFR2 in persistent eGFR decline. Additionally, an ROC curve analysis was conducted to assess the prognostic value of TNFR2 in predicting persistent eGFR decline among MGN patients. Results We assessed the levels of inflammatory markers TNF-α and TNFR2, examined their correlation with eGFR and renal injury, and investigated their potential in predicting persistent eGFR. Patients with MGN exhibited elevated levels of TNFR2 in their serum, urine, and gene expression compared to healthy individuals. Additionally, there was a positive correlation between serum TNFR2 and TNF-α, urine protein-creatinine ratio (UPCR), uric acid, and total cholesterol. Conversely, there was a negative correlation with eGFR, serum albumin, and calcium. Serum TNFR2 showed statistical significance in a univariate Cox regression analysis (HR: 1.010, 95% CI: 1.00-1.01, p = 0.045) for predicting a persistent decline in eGFR. However, it did not show significance concerning relapse and remission. An ROC curve was created to assess TNFR2's prognostic potential as a biomarker, demonstrating an AUC of 0.683, with a sensitivity of 68% and specificity of 64%. Conclusions Based on our findings, TNFR2 is a predictive biomarker for eGFR decline in MGN, correlating with renal inflammation and predicting deterioration in renal function. TNFR2 emerges as a promising biomarker for early identification in patients at risk of renal function decline.

Prognostic Impact of Proteinuria at Manifestation in Adult Nephrotic Syndrome Patients: Insights from a Prospective Cohort Study.

Background and objective Nephrotic syndrome is a significant worldwide health concern impacting millions of people and is marked by heavy proteinuria, edema, and decreased serum levels of albumin. Albuminuria arises from abnormal glomerular permeability and impaired tubular reabsorption, contributing to declining kidney function and a heightened risk of cardiovascular complications. The objective of this study was to investigate the prognostic role of proteinuria on the persistent decline in estimated glomerular filtration rate (eGFR) (<30 ml/minute/1.73m2) during follow-up and the dynamics of remission and relapse in various subtypes of nephrotic syndrome. Methods A total of 134 adult patients, diagnosed with various histopathological categories of nephrotic syndrome, were prospectively studied. Urine protein levels were assessed using the pyrogallol red-molybdate (PRM) method. The Kaplan-Meier analysis and log-rank test were utilized to assess the prognostic role of proteinuria at manifestation on persistent decline in estimated glomerular filtration rate (eGFR) (<30 ml/minute/1.73m2) and to evaluate remission and relapse based on proteinuria levels over an 18-month follow-up period. Results Patients with sub-nephrotic levels of proteinuria at manifestation did not progress to end-stage renal disease on follow-up. Patients with sub-nephrotic levels of albuminuria at manifestation were significantly associated with remission on follow-up. The Kaplan-Meier analysis indicated a significant probability of persistent eGFR decline (p < 0.001) in adult nephrotics with higher levels of albuminuria. Furthermore, patients with sub-nephrotic range proteinuria had earlier remission (p < 0.001) compared to those with relapse (p = 0.001) during the follow-up, as demonstrated by log-rank tests. Conclusion This study highlights that sub-nephrotic albuminuria at manifestation is linked to a reduced risk of renal progression and persistent eGFR decline compared to adult nephrotics with higher levels of albuminuria. Early detection and effective management of proteinuria, are crucial for preventing renal function decline and improving patient outcomes.

Morphology, Morphometry, and Immunohistochemical Profile of Megakaryocytes and Bone Marrow Microenvironment in Disease Progression and Therapy Resistance in Chronic Myeloid Leukemia.

Background Tyrosine kinase inhibitors have revolutionized the treatment of chronic myeloid leukemia (CML) since the beginning of the century. However, resistance to therapy and the progression of disease tend to occur in certain patients. The bone marrow microenvironment may play a role in the disease outcome. Megakaryocytes have multiple roles in the regulation and maintenance of the hematopoietic stem cell microenvironment. In the current study, we evaluated the association of megakaryocyte morphology, morphometry, and microenvironment with disease progression and therapy resistance in CML. Methodology Megakaryocyte morphology and morphometry were analyzed and compared between the different phases (chronic and advanced) at diagnosis in 150 cases of BCR-ABL-positive CML. All CML-CP patients (n = 119) were followed up on tyrosine kinase inhibitor therapy for a minimum of 15 months and classified based on their treatment outcome as a response, resistance to therapy, or progression of disease based on standard criteria. Immunohistochemistry on a bone marrow trephine biopsy was done for vascular endothelial growth factor (VEGF), FOXP3, CD150, CD48, CD44, osteopontin, CXCL12, N-cadherin, PDL-1, and IL-7, and their expression on megakaryocytes and their association with treatment outcome was evaluated. Results The morphology and morphometry of megakaryocytes showed a heterogeneous population in CML. Morphology and morphometric parameters, when compared between the chronic and advanced phases of disease at diagnosis, did not show any statistical difference. Megakaryocytes were variably positive for VEGF, FOXP3, CD150, CD48, osteopontin, N-cadherin, CXCL12, CD44, PDL-1, and IL-7. However, only CD44-positive megakaryocytes were statistically associated with the treatment outcome. The patients with a higher expression of CD44 megakaryocytes progressed to the advanced phase of the disease during therapy compared to those who responded. Conclusion Megakaryocyte morphology and morphometry were heterogeneous in CML; however, they did not show any significant difference with either the phase of the disease or with treatment outcomes. Among the various immunohistochemical markers of the microenvironment, only CD44-positivity on megakaryocytes was associated with poor treatment outcomes.

Assessment of novel prognostic biomarkers to predict pathological complete response in patients with non-metastatic triple-negative breast cancer using a window of opportunity design.

Background: Triple-negative breast cancer (TNBC) includes approximately 20% of all breast cancer and is characterized by its aggressive nature, high recurrence rates, and visceral metastasis. Pathological complete response (pCR) is an established surrogate endpoint for survival. The window of opportunity studies provide valuable information on the disease biology prior to definitive treatment. Objectives: To study the association of dynamic change in pathological, imagining, and genomic biomarkers that can prognosticate pCR. The study aims to develop a composite prognostic score. Design: Clinical, interventional, and prognostic biomarker study using the novel window of opportunity design. Methods: The study aims to enroll 80 treatment-naïve, pathologically confirmed TNBC patients, administering a single dose of paclitaxel and carboplatin during the window period before neoadjuvant chemotherapy (NACT). Tumor tissue will be obtained through a tru-cut biopsy, and positron emission tomography and computed tomography scans will be performed for each patient at two time points aiming to evaluate biomarker alterations. This will be followed by the administration of standard dose-dense NACT containing anthracyclines and taxanes, with the study culminating in surgery to assess pCR. Results: The study would develop a composite prognostic risk score derived from the dynamic change in the Ki-67, tumor-infiltrating lymphocytes, Standardized Uptake Value (SUV max), Standardized Uptake Value for lean body mass (SUL max), and gene expression level pre- and post-intervention during the window period prior to the start of definitive treatment. This outcome will aid in categorizing the disease biology into risk categories. Trial registration: The current study is approved by the Institutional Ethics Committee [Ethics: Protocol. no. JIP/IEC/2020/019]. This study was registered with ClinicalTrials.gov [CTRI Registration: CTRI/2022/06/043109]. Conclusion: The validated biomarker score will help to personalize NACT protocols in patients in TNBC planned for definitive treatment.

Precision in action: unveiling predictive biomarkers for enhanced TNBC treatment We are investigating new ways to predict how well a particular treatment will work in patients with a specific type of breast cancer called triple-negative breast cancer. The study goal is to find biomarkers that change in response to drugs to predict the complete elimination of cancer in patients before it spreads to other parts of the body. To do this, we are using a special research approach called a 'window of opportunity design.' This information could be valuable in personalizing and improving cancer treatments.

Reproducibility and prognostic ability of chronicity parameters in kidney biopsy - Comprehensive evaluation comparing microscopy and artificial intelligence in digital pathology.

INTRODUCTION: Semi-quantitative scoring of various parameters in renal biopsy is accepted as an important tool to assess disease activity and prognostication. There are concerns on the impact of interobserver variability in its prognostic utility, generating a need for computerized quantification. METHODS: We studied 94 patients with renal biopsies, 45 with native diseases and 49 transplant patients with index biopsies for Polyomavirus nephropathy. Chronicity scores were evaluated using two methods. A standard definition diagram was agreed after international consultation and four renal pathologists scored each parameter in a double-blinded manner. Interstitial fibrosis (IF) score was assessed with five different computerized and AI-based algorithms on trichrome and PAS stains. RESULTS: There was strong prognostic correlation with renal function and graft outcome at a median follow-up ranging from 24 to 42 months respectively, independent of moderate concordance for pathologists scores. IF scores with two of the computerized algorithms showed significant correlation with estimated glomerular filtration rate (eGFR) at biopsy but not at the end of follow-up. There was poor concordance for AI based platforms. CONCLUSION: Chronicity scores are robust prognostic tools despite interobserver reproducibility. AI-algorithms have absolute precision but are limited by significant variation when different hardware and software algorithms are used for quantification.

Pericanalicular eccrine hidrocystoma of the upper eyelid in a child.

A rare case of pericanalicular eccrine hidrocystoma of the upper eyelid is reported in a child who underwent surgical excision and canalicular repair with a successful outcome.

Cleistanthins A and B Ameliorate Testosterone-Induced Benign Prostatic Hyperplasia in Castrated Rats by Regulating Apoptosis and Cell Differentiation.

Background The aging male population is at higher risk for benign prostatic hyperplasia (BPH) wherein increased proliferation of stromal and epithelial cells of the prostate is observed. In this study, we investigated the effect of cleistanthins A and B on the inhibition of testosterone-induced BPH in castrated rats. Methodology Male Wistar rats were divided into eight groups (n = 6) and surgical castration was performed. BPH was induced by the administration of testosterone propionate in corn oil at 5 mg/kg for four weeks. The control group received corn oil, and the model group received testosterone propionate. The standard treatment group received finasteride orally along with testosterone. Cleistanthins A and B at 0.3, 1, and 3 mg/kg were administered by oral gavage along with testosterone. After four weeks, rats were sacrificed, and prostates were weighed and assessed for histomorphological, inflammatory, apoptotic, and proliferative markers. Results Cleistanthins A and B decreased prostatic enlargement and histopathological abnormalities. Elevated serum dihydrotestosterone levels were lowered significantly in both the cleistanthin A and cleistanthin B groups compared to the BPH model group. Cleistanthins A and B significantly lowered the serum interleukin (IL)-1ß and tumor necrosis factor-alpha inflammatory markers in the test groups. Western blot analysis revealed cleistanthin A downregulated the IL-6, signal transducer and activator of transcription 3/cyclin D1 signaling pathway. Both cleistanthins A and B upregulated the apoptotic markers caspase-3 and cleaved caspase-3, whereas the cell proliferation markers cyclin D1 and proliferating cell nuclear antigen were found to be downregulated. Conclusions Both cleistanthins A and B inhibited BPH in a rat model by apoptotic induction and impeded cell proliferation.

Malignant Nodular Hidradenoma of the Left Knee: A Malignant Mystery With an Overview of Literature.

Malignant nodular hidradenoma is a rare eccrine sweat gland neoplasm characterized by recurrence, metastasis, and a locally aggressive course. In our case report, a 74-year-old man presented with a seemingly benign swelling which was persistent for the last 30 years, which was excised at an outside institute. Since the patient presented to the hospital during the peak of the pandemic, considering the age of the patient, the pandemic situation, the logistics of radiotherapy during such a situation, preserving the knee joint function in view of close proximity of the tumour to the joint, it was decided to keep the patient on follow up and continue expectant management. After a follow-up period of 24 months, no locoregional recurrence or metastasis has been observed. The patient is on annual follow-up with clinical examination and PET-CECT imaging.

Identification of Differentially Expressed Mirna by Next Generation Sequencing in Locally Advanced Breast Cancer Patients of South Indian Origin.

PURPOSE: miRNAs are known to be aberrantly expressed in the serum, tissue, and Peripheral Blood Mononuclear Cells (PBMC) of cancer patients and could serve as potential noninvasive diagnostic markers for breast cancer. The aim of this study was to identify the differentially expressed miRNA using next-generation sequencing (NGS) from the paired PBMC samples from breast cancer patients and age-matched healthy individuals and explore their functional significance. METHODS: In this study, PBMCs were employed for the detection of miRNAs by NGS in locally advanced breast cancer (LABC) women of South Indian origin who were divided into three age groups, (a) 40yrs-50yrs (b) 50yrs-60yrs and (c) 60yrs-70yrs, compared with age-matched control groups. RESULTS: Four miRNAs (hsa-miR-192-5p, hsa-miR-24-2-2p, hsa-miR-3609, and hsa-miR-664b-3p) were found to be differentially expressed among LABC patients compared with age matched healthy women of the South Indian population. While miR-24-2-5p, miR3609, and miR-664b-3p were down-regulated, miR-192-5p was up-regulated. Gene Ontology (GO) annotations implicated miRNA with signaling pathways in peripheral nerve synapses, glutamatergic synapse, and cell morphogenesis, all of which play a pivotal role in the manifestation of cancer. CONCLUSION: Four miRNAs- 3 (While miR-24-2-5p, miR3609, and miR-664b-3p) downregulated and one upregulated (miR-192-5p) were identified as potential biomarkers for patients with locally advanced breast cancer. These markers could be validated in studies with a larger sample size.

Revisit of Polyomavirus Nephropathy Grading in Renal Allograft Recipients According to the Banff 2019 Working Group Classification: A Study From a Large Transplant Center in South India.

Background In renal transplant patients, the biopsy-proven incidence of polyomavirus nephropathy (PVN) is approximately 5%. There is no consensus in the morphologic classification of definitive PVN, which is attempted in the Banff 2019 Working Group classification, which groups histologic changes, reflects clinical presentation, and facilitates comparative outcome analyses. This study aims to analyze the clinical and histopathological findings and outcomes among the three classes in the recent classification. Materials and methods The study was conducted in the department of pathology and nephrology over a period of six years. All cases diagnosed as PVN on renal allograft biopsies were included. The clinical and biochemical findings were obtained from hospital records. Histopathology slides were reviewed and classified according to Banff 2019 criteria and were analyzed with clinical, laboratory, histopathological parameters along with the clinical outcome. Results Out of 205 renal transplants performed during the study period, 14 patients (6.8%) were diagnosed with PVN. The mean age of diagnosis was 38 years, with a Male: Female ratio of 1.8:1. The median period of diagnosis of the viral infection after transplant was 10 months. Histomorphology grading according to Banff 2019 revealed four cases (28.5%) in PVN class 1, eight cases (57.2%) in PVN class 2, and two cases (14.3%) in PVN class 3. Cases in PVN class 1 presented early. PVN class 1 was associated with a single type of inclusion, and multiple type inclusions were observed in higher classes. Associated diseases were thrombotic microangiopathy (TMA), borderline cellular rejection, antibody-mediated rejection (ABMR), and concomitant infections. PVN class 1 had a better outcome compared to PVN class 2 and class 3. Conclusion PVN1 was observed to have better clinical presentation and outcomes than PVN2 and 3; however, this could not be statistically concluded due to the low sample size and other associated diseases.

Assessment of Organophosphate Pesticides Exposure in Men with Idiopathic Abnormal Semen Analysis: A Cross-Sectional Pilot Study.

BACKGROUND: Because of the widespread use of organophosphate (OP) pesticides in agriculture, they are major environmental contaminants in developing countries. OP pesticides decrease sperm concentration and affect its quality, viability, and motility. studies have demonstrated the association between abnormal semen analysis and OP pesticides exposure among the high-risk population. Asthere is limited data on the percentage of OP pesticides exposure, the study aimed to determine the OP pesticides exposure in Southern Indian men with idiopathic abnormal semen analysis and find the possible source of their OP pesticides exposure. MATERIALS AND METHODS: In this cross-sectional pilot study, fifty men with idiopathic abnormal semen analysis as cases and fifty men with normal semen analysis as controls were recruited. Detailed history wastaken and general and systemic examinations were carried out. OP pesticides exposure was determined by assessment of pseudocholinesterase and acetylcholinesterase levels and urinary OP pesticides metabolites dialkyl phosphate (DAP) consisting of dimethyl phosphate (DMP), diethyl thiophosphate (DETP), and diethyl dithiophosphate (DEDTP). RESULTS: Cases had statistically significantly lower levels of pseudocholinesterase (5792.07 ± 1969.89 vs. 10267.01 ± 3258.58 IU/L) (P=0.006) and acetylcholinesterase [102.90 (45.88-262.74) vs. 570.31 (200.24-975.30) IU/L] (P=0.001) as compared to controls. Cases had a statistically significantly higher percentage of urinary DAP positivity as compared to controls (80 vs. 38%, P<0.0001). Hence, cases had a significantly higher percentage of OP pesticides exposure as compared to controls (20 vs. 4 %, P=0.015). OP-exposed cases had significantly higher urinary DETP and DEDTP levels as compared to OP non-exposed cases. Also, urinary DETP and DEDTP levels were significantly negatively associated with sperm concentration, motility, and normal morphology among OP-exposed cases. CONCLUSION: Southern Indian men with idiopathic abnormal semen analysis had a significantly higher percentage of OP pesticides exposure as compared to men with a normal semen analysis.

Intestinal Obstruction Due to Giant Bilateral Krukenberg's Tumors Synchronous of Colorectal Origin.

Giant bilateral Krukenberg tumors are rarely seen, especially causing complications due to their size. We present a 35-year-old female, diagnosed with carcinoma rectum one year back, now presented to us with intestinal obstruction features. Imaging was suggestive of features of acute intestinal obstruction. Intraoperatively, we found that the patient had bilateral giant ovarian cysts, which compressed the proximal part of the descending colon, causing the obstruction. The patient underwent bilateral excision of the ovarian cyst with diversion sigmoid colostomy. Postoperatively the patient was started on palliative chemotherapy.