Relation of Langerhans cell size to buccal carcinoma.

Oral cancer decreases quality of life despite timely medical management. The carcinogens in tobacco products and their role in tumorigenesis are well documented. Langerhans cells (LCs) are a subset of antigen-presenting cells (APCs) that monitor the tumor microenvironment and engulf carcinogens and foreign bodies. We investigated the distribution and size of LCs and their relation to the mode of tobacco consumption and clinical outcome in patients with buccal carcinoma. We recruited patients with oral cancer who were scheduled for tumor excision and men with urethral stricture undergoing substitution urethroplasty using buccal mucosa. Normal and tumor-adjacent tissues were stained with CD1a antibody. The distribution and mean diameter of 100 LCs/patient were determined. We found significantly smaller LCs in patients who chewed only tobacco compared to those who consumed tobacco by other means. The size of LCs decreased significantly with progressive stages of malignant disease. We found that patients with larger LCs survived longer than those with smaller LCs during an average follow-up of 24 months. We suggest a relation between the size of LCs and clinical outcomes in patients with buccal carcinoma.

Comparative analysis of mutational patterns in triple negative breast cancer before and after neoadjuvant chemotherapy in patients with residual disease.

Triple-negative breast cancer (TNBC) is a heterogeneous disease with poor survival compared to other subtypes. Patients with residual disease after neoadjuvant chemotherapy (NAC) face an increased risk of relapse and death. We aimed to characterize the mutational landscape of this subset to offer insights into relapse pathogenesis and potential therapeutic targets. We retrospectively analyzed archived paired (pre- and post-NAC) tumor samples from 25 patients with TNBC with residual disease using a targeted 72-gene next-generation sequencing panel. Our findings revealed a stable mutational burden in both pre- and post-NAC samples, with a median count of 12 variants (IQR 7-17.25) per sample. TP53, PMS2, PTEN, ERBB2, and NOTCH1 variants were observed in pre-NAC samples predominantly. Notably, post-NAC samples exhibited a significant increase in AR gene mutations, suggesting potential prognostic and predictive implications. No difference in mutational burden was found between patients who did and did not receive platinum (p = 0.94), or between those with and without recurrence (p = 0.49). We employed K-means clustering to categorize the patients based on their variant profiles, aiding in the prediction of possible patterns associated with recurrence. Our study was limited by its small sample size and retrospective design, suggesting the need for further validation in larger prospective cohorts.

Analysis of patients with endometrial carcinoma using the ProMise classifier: a pilot study from India.

BACKGROUND: Molecular subtyping of endometrial carcinomas (EC) has been shown to classify tumors into prognostically relevant groups. Characterizing EC with a limited number of markers viz., POLE mutations, p53 mutations, and MMR status, can provide valuable information. DESIGN: Paraffin sections of a cohort of 48 EC from a tertiary care center were characterized for the above-mentioned molecular markers and analyzed in the context of survival. METHODS: Formalin fixed paraffin embedded tissues from 48 EC were characterized for POLE mutations by Sanger sequencing (exons 9-14), for MMR (MLH1, MH2, MSH6) using immunohistochemistry (IHC) and copy number (high/low) using p53 IHC. Mutational status was integrated along with the clinicopathological details and survival analysis performed. RESULTS: Eleven (22.9%) patients were MMR deficient, 3 (6.3%) had POLE mutation, while 2 (4.1%) had both POLE and P53 mutations (regarded as multiple classifiers). Twelve (25%) patients were found to have P53 mutations, while the remaining 20 (41.7%) had no specific molecular profile (NSMP). Median follow-up duration was 43.5 (2-62) months with 8 recurrences and 9 deaths. Tumors with POLE mutation had the most favorable prognosis followed by the NSMP and the MMR mutated group while the P53 and multiple classifier groups had the worst prognosis in terms of OS (Log-rank p: 0.006) and PFS (Log-rank p: 0.001). CONCLUSION: The integration of molecular-clinicopathologic data for endometrial cancer classification, through cost-effective, clinically applicable assays appears to be a highly objective tool that can be adopted even in resource-limited settings. It has the potential to cause a shift in the paradigm of EC pathology and management practice.

Threshold and suprathreshold component analysis in olfactory dysfunction: a retrospective study.

OBJECTIVE: To analyse variations in the n-butanol threshold and odour identification scores of the Connecticut Chemosensory Clinical Research Centre test in various grades of olfactory dysfunction and in different nasal conditions leading to olfactory loss. METHOD: Retrospective observational study. RESULTS: All grades of olfactory dysfunction were predominantly noted among males. In chronic rhinosinusitis, anosmia or severe hyposmia was seen in 87.5 per cent of patients without polyps in comparison with 68 per cent of patients with polyps. In addition, 90 per cent of patients with atrophic rhinitis and post-traumatic loss had anosmia, but only 30.7 per cent of patients with allergic rhinitis had anosmia. Pepper was the most affected smell for all the nasal diseases except atrophic rhinitis, in which asafoetida and baby powder smells were affected more. CONCLUSION: In most inflammatory sinonasal conditions, odour identification is relatively preserved even when the threshold is maximally affected. In patients with comparable olfactory dysfunction based on the Connecticut Chemosensory Clinical Research Centre test score, a relatively preserved suprathreshold odour identification score may predict better prognosis.

Dose-Dense Docetaxel-Cyclophosphamide and Epirubicin-Cisplatin(ddDCEP): Analysis of an Alternative Platinum-Containing Regimen in 116 Patients with Early Triple Negative Breast Cancer.

We assessed the efficacy, tolerability, and cost-effectiveness of a novel neoadjuvant regimen comprising docetaxel-cyclophosphamide alternating with epirubicin-cisplatin (ddDCEP) administered biweekly for 16 weeks in 116 patients with early triple-negative breast cancer. This regimen achieved a high pathological complete response (ypT0/TisN0) rate of 55.2% and favorable survival outcomes (30-month event-free survival, 91.2%; overall survival, 97%). Febrile neutropenia was observed in 4.3% of patients, and 98% completed at least six of eight cycles. ddDCEP was more cost-effective than contemporary carboplatin-based regimens. This novel approach offers an economically viable and effective alternative to current chemoimmunotherapy regimens, and merits further investigation.

Clinico-Radiological Evaluation for Longitudinal Assessment in Central Skull Base Osteomyelitis: Proposal of Novel Scoring System.

This study aims to evaluate clinical, radiological and laboratory parameters for longitudinal assessment and prognostication in central skull base osteomyelitis (CSBO). Novel radiological score and cranial nerve assessment score (CNAS) have been proposed and analysed along with pain score (VAS), ESR, CRP, WBC count, and HbA1c for utility in disease-monitoring and predicting outcome in CSBO. CSBO cases managed in a tertiary care centre from January 2018 to November 2020, with a minimum follow-up of 6 months were included. The parameters were recorded at presentation, 3-month, 6-month postoperative follow-up, and at completion of therapy, for statistical analysis. Significant positive correlation was found amongst pain score, CNAS, radiological score, ESR, and CRP at different timelines. On longitudinal assessment, there was a statistically significant reduction in above-mentioned parameters, in the cases who recovered. Those with initial radiological score < 30, pain score ≤ 7, and CNAS < 10 showed early clinical improvement, required shorter duration of antimicrobial therapy, and exhibited higher probability of becoming disease-free at an earlier time, compared to those presenting with higher scores. We propose the use of pain score, a novel cranial nerve assessment score, and a novel radiological score for longitudinal assessment in CSBO. The trend in these parameters along with ESR and CRP are useful to monitor the disease process. The initial assessment scores can predict duration of antimicrobial therapy and probability of early recovery. WBC count and HbA1c were neither useful for disease-monitoring nor predicting outcome.

Understanding the predictive accuracy of the InsuTAG index over other surrogate indices in normoglycaemic, non-obese males from Southern India.

We aimed to evaluate the predictive accuracy of InsuTAG index against M value of the hyperinsulinaemic-Euglycaemic clamp (HEC) procedure and fasting surrogate indices of insulin sensitivity/resistance in young, normoglycaemic, Asian Indian males. HEC studies were done in young (mean age 19.7 ± 1 years), non-obese (mean BMI 19.2 ± 2.6 kg/m2), normoglycemic Asian Indian males (n = 110) and the M value was calculated. Surrogate indices namely InsuTAG index, HOMA-IR, FG-IR, QUICKI and McAuley index were calculated. Pearson's correlation and ROC-AUC at 95% CI were applied. Significant negative correlation was observed for InsuTAG index with the M value (r - 0.23, p = 0.01), McAuley index (r - 0.65, p < 0.01), QUICKI (r - 0.34, p < 0.01) and FGIR (r - 0.35, p < 0.01). Significant positive correlations of InsuTAG index were observed for BMI and waist circumference. The ROC-AUC was higher for InsuTAG index (0.75) than FGIR (0.30), QUICKI (0.31), and McAuley index (0.20). The InsuTAG cut-off value ≥ 19.13 showed 66.7% sensitivity and 69.2% specificity in this study group.

Comparative evaluation of diabetic retinopathy screening programs in regular ophthalmology clinics versus integrated diabetic clinics within rural health-care services.

BACKGROUND: Robust integration of diabetic retinopathy (DR) screening within health systems is essential to prevent DR-related blindness. This, however, remains a challenge in the developing world. The aim of this study was to evaluate two models of DR screening programs within rural general health-care services. MATERIALS AND METHODS: This was a retrospective observational study from two rural health centers. Demographic and clinical data of patients completing DR screening were analyzed. Patients were screened in regular ophthalmology clinics (ROC) or integrated diabetic clinics (IDC). Referral and treatment completion data were retrieved from the clinical charts at the base hospital. RESULTS: A total of 2535 DR screenings were conducted for 2296 patients. The total population prevalence for any DR was 14.2% (95% confidence interval [CI]: 12.8%-15.6%) and vision-threatening DR (VTDR) was 4.7% (95% CI: 3.8%-5.6%). In the ROC and IDC groups, respectively, the prevalence of any DR was 20.4% and 8.2%, VTDR, 7.8% and 1.7%, and blindness, 1.4% and 0.4% (all P < 0.001). Referral completion rates were higher in the ROC group (44.8% vs. 25.2%, P < 0.001), while treatment completion in both was similar (69.6% vs. 70.6%). Referral and treatment completion rates for referable DR were 61.2% and 48.2%, and for VTDR, 62% and 38.8%, respectively. Only 11.45% of patients completed the repeat screening follow-up. CONCLUSIONS: Patients attending IDCs had a significantly lower prevalence of any DR, VTDR, and blindness demonstrating the advantages of integrated diabetic care in a rural setting. However, referral uptake and DR treatment completion need strengthening.

Bone Mineral Density and Serum Bone Turnover Markers among Post-Menarchal Girls from Rural South India.

Background: The data on the bone mineral density (BMD) and bone turnover markers (BTMs) in Indian adolescents are limited. Objectives: To assess BMD at lumbar spine (LS, L1-L4) and femoral neck (FN) in South Indian post-menarchal girls and correlate it with dietary calcium intake (mg/day), physical activity score and post-menarchal years. The study also assessed serum BTMs and their correlation with chronological age in the study population. Methods: This cross-sectional study included apparently healthy post-menarchal adolescent girls aged 12-16 years randomly selected from the community. Participants with vitamin D deficiency were excluded. The data on calcium intake and physical activity were obtained using validated questionnaires. All participants were evaluated with serum calcium, 25-hydroxy vitamin D, parathyroid hormone, N-terminal propeptide of type 1 collagen (P1NP) and Beta-CrossLaps (CTx) and BMD at LS and FN using dual X-ray absorptiometry (DXA). Statistical Analysis: EpiData version 3.1 was used for the data entry. The data analysis was done using Statistical Package for Social Sciences (SPSS) version 21. Continuous variables were expressed as mean ± SD. Pearson's correlation coefficient (r) was calculated, and two-tailed Kendall's tau-b test was used for assessing correlation of all nonparametric measures. Results: A total of 103 participants were screened, and data from 77 were analysed. There was a significant positive correlation of BMD at LS with chronological age (r: +0.235, P = 0.036), but not at FN. Positive correlation of BMD with increase in post-menarchal years was also noted at LS (r: +0.276, P = 0.015). There was no significant association of BMD with calcium intake and physical activity scores at both sites. There was a significant negative correlation of serum BTMs with age CTx (r: -0.596, P = 0.0001) and P1NP (r: -0.505, P = 0.0001). Conclusion: This study provides insight into the reference BMD range at LS spine and FN in South Indian rural post-menarchal adolescent girls. BMD positively correlated, whereas BTMs negatively correlated with age. The study also provides the first Indian reference range for serum BTMs in this age group.

Relationship of Upper Airway Collapse with Severity of Sleep Apnoea and Sleepiness.

Introduction: Obstructive sleep apnoea (OSA) is characterized by repeated episodes of upper airway collapse. A review of literature shows limited and conflicting data regarding impact of upper pharyngeal collapse on severity of OSA and degree of sleepiness. Objective: To evaluate the association of the number of levels and degree of upper airway collapse and severity of OSA. Methods: This is a retrospective study including all patients with OSA over a two-year period. Data regarding neck circumference (NC), body mass index (BMI), nasopharyngolaryngoscopy with Muller's manoeuvre, Epworth sleepiness scale (ESS) questionnaire and a full night polysomnography were collected. Correlation of the number of sites involved and degree of collapse at each site (velum, lateral pharyngeal wall- Level I, base of tongue - Level II and epiglottis - Level III) with BMI, NC, AHI and ESS were assessed. Results: Of the 144 patients, 98% had collapse at Level I. 80% of patients had multisegmental collapse with 30% having collapse at all three levels. The number of levels and the severity of collapse did not have a proportionate effect on the AHI and ESS and were not directly dependent on the BMI. However, changes in NC had a significant effect on the severity of collapse.Conclusion: Severity of OSA and degree of sleepiness were not directly dependent on the severity and the number of levels of collapse. Since majority of the patients had multi segmental collapse, the study highlights the importance of careful assessment of all levels to tailor management strategies for optimum patient management.

Human fetal cartilage-derived chondrocytes and chondroprogenitors display a greater commitment to chondrogenesis than adult cartilage resident cells.

Obtaining regeneration-competent cells and generating high-quality neocartilage are still challenges in articular cartilage tissue engineering. Although chondroprogenitor cells are a resident subpopulation of native cartilage and possess a high capacity for proliferation and cartilage formation, their potential for regenerative medicine has not been adequately explored. Fetal cartilage, another potential source with greater cellularity and a higher cell-matrix ratio than adult tissue, has been evaluated for sourcing cells to treat articular disorders. This study aimed to compare cartilage resident cells, namely chondrocytes, fibronectin adhesion assay-derived chondroprogenitors (FAA-CPCs) and migratory chondroprogenitors (MCPs) isolated from fetal and adult cartilage, to evaluate differences in their biological properties and their potential for cartilage repair. Following informed consent, three human fetal and three adult osteoarthritic knee joints were used to harvest the cartilage samples, from which the three cell types a) chondrocytes, b) FAA-CPCs, and MCPs were isolated. Assessment parameters consisted of flow cytometry analysis for percentage expression of cell surface markers, population doubling time and cell cycle analyses, qRT-PCR for markers of chondrogenesis and hypertrophy, trilineage differentiation potential and biochemical analysis of differentiated chondrogenic pellets for total GAG/DNA content. Compared to their adult counterparts, fetal cartilage-derived cells displayed significantly lower CD106 and higher levels of CD146 expression, indicative of their superior chondrogenic capacity. Moreover, all fetal groups demonstrated significantly higher levels of GAG/DNA ratio with enhanced uptake of collagen type 2 and GAG stains on histology. It was also noted that fetal FAA CPCs had a greater proliferative ability with significantly higher levels of the primary transcription factor SOX-9. Fetal chondrocytes and chondroprogenitors displayed a superior propensity for chondrogenesis when compared to their adult counterparts. To understand their therapeutic potential and provide an important solution to long-standing challenges in cartilage tissue engineering, focused research into its regenerative properties using in-vivo models is warranted.

Comparison of methods for the isolation and culture of Migratory chondroprogenitors from Human articular cartilage.

PURPOSE: Resident articular stem cells isolated using a migratory assay called Migratory Chondroprogenitors (MCPs) have emerged as a promising cellular therapeutic for the treatment of cartilage pathologies. In-vivo studies using MCPs report their superiority over bone-marrow mesenchymal stem cells and chondrocytes for treating chondral defects. However, there is no consensus on their isolation protocol. This study aimed to compare four reported isolation methods of MCPs and identify the optimal and feasible protocol for future translational work. METHODS: Human MCPs isolated from osteoarthritic cartilage (n = 3) were divided into four groups: a) MCP1: 8-15 mm cartilage explants, b) MCP2: 8-10 mm explants digested in 0.1% collagenase for 2 hrs. and cultured c) MCP3: 1 mm cartilage explants and d) MCP 4: 25 mm explants with a X tear, 7-day culture, and trypsinization to release migrated cells. The MCPs were subjected to the following analysis: growth kinetics, surface marker expression, mRNA gene expression for markers of chondrogenesis and hypertrophy, and trilineage differentiation. RESULTS: MCPs isolated via the four methods showed similar surface marker profiles, chondrogenic (SOX-9, ACAN, COL2A1) and hypertrophic (COL1, RUNX2) gene expression. The migration time for the MCP3 group was the longest. The MCP1, MCP2, and MCP4 groups produced MCPs with comparable cellular expansion feasibility. CONCLUSIONS: MCPs can be preferably isolated by the any of the three above methods based on the investigator's discretion. In the case of small cartilage samples similar to the MCP3 group, the isolation of MCP is plausible, keeping in mind the additional time required.

Longitudinal assessment of HCV core antigen kinetics to monitor therapeutic response in the age of DAAs.

BACKGROUND: In the economy of therapeutic monitoring, an affordable viral marker is essential in the era of direct-acting antivirals (DAAs). We elucidated the kinetics of HCVcAg to delineate its precise role in monitoring therapeutic response. METHODS: In this longitudinal study, 3208 patients were tested for HCV RNA. A total of 423 patients were started on DAAs. Treatment response and kinetics of HCVcAg/RNA were assessed in treatment-naïve (n = 383) and previously treated (n = 40) patients with follow-up for 2 years. RESULTS: After the initiation of DAAs, the rate of relapse was significantly higher in the previously treated group than naive group [12.5% (5/40) Vs 2% (7/383), p<0.0001]. The response rate at RVR was significantly higher with HCVcAg than RNA in both groups (p<0.02). The kinetics of HCVcAg and RNA were significantly different at ETR and SVR12 in the naïve (p<0.04), but similar at all therapeutic points in the previously treated group. The correlation between HCVcAg and RNA was good at baseline, ETR and SVR, except RVR in both groups (r>0.6; p<0.0001). Furthermore, HCV genotypes, treatment regimen, CTP (<7/≥7) and MELD (<15/≥15) did not influence the therapeutic response and the viral replication kinetics (p>0.05). CONCLUSIONS: It is the first longitudinal study from India shows that the response rate and kinetics of HCVcAg are comparable to HCV RNA for an extended duration, except at RVR, irrespective of the HCV genotypes, treatment regimen, and liver disease severity. Hence, HCVcAg can be considered as a pragmatic marker to monitor therapeutic response and predict relapse in the era of DAAs.

Usefulness of urinary calprotectin as a novel marker differentiating functional from structural acute kidney injury in the critical care setting.

BACKGROUND: Biomarkers are fundamental tools for differentiating between types of acute kidney injury (AKI) and may thus be crucial in management and prognosis. We report on a recently described biomarker, calprotectin, that appears to be a promising candidate in differentiating hypovolemic/functional AKI from intrinsic/structural AKI, whose acknowledgement may play a role in improving outcomes. We aimed to study the efficacy of urinary calprotectin in differentiating these two forms of AKI. The effect of fluid administration on the subsequent clinical course of AKI, its severity and the outcomes were also studied. METHODOLOGY: Children who presented with conditions predisposing to AKI or with diagnosis of AKI were included. Urine samples for calprotectin analysis were collected and stored at - 20 ºC for analysis at the end of the study. Fluids were administered as per clinical conditions, followed by intravenous furosemide 1 mg/kg, and patients were observed closely for at least 72 h. Children with serum creatinine normalization and clinical improvement were classified as with functional AKI, while those with no response were classified as with structural AKI. Urine calprotectin levels between these two groups were compared. Statistical analysis was performed with SPSS 21.0 software. RESULTS: Of the 56 children enrolled, 26 were classified as with functional AKI and 30 as with structural AKI. Stage 3 AKI was observed in 48.2% of patients and stage 2 AKI in 33.8%. Mean urine output, creatinine and stage of AKI improved with fluid and furosemide or furosemide alone (OR 6.08, 95% CI 1.65-27.23) (p < 0.01). A positive response to fluid challenge was in favor of functional AKI (OR 6.08, 95% CI 1.65-27.23) (p = 0.008). Presence of edema, sepsis and need for dialysis were hallmarks of structural AKI (p < 0.05). Urine calprotectin/creatinine values were 6 times higher in structural AKI compared to functional AKI. Urine calprotectin/creatinine ratio showed the best sensitivity (63.3%) and specificity (80.7%) at a cut-off value of 1 mcg/mL in differentiating the two types of AKI. CONCLUSION: Urinary calprotectin is a promising biomarker that may help differentiating structural from functional AKI in children.

Orthotic walking outcome of persons with motor complete low thoracic spinal cord injury-a retrospective study.

STUDY DESIGN: Retrospective study. OBJECTIVE: To analyse the orthotic walking outcome of patients with Low Thoracic Spinal Cord Injury (LT-SCI). SETTING: The Rehabilitation Institute at Christian Medical College, Vellore, India. METHODS: Data between January 2005 and June 2015 were retrospectively collected from electronic medical reports of patients with motor complete LT- SCI who were admitted for the comprehensive rehabilitation program. The orthotic walking outcome of these patients was measured by the Walking index for SCI version II (WISCI II). Demographical and clinical parameters were measured and their association with the walking outcome was analyzed using regression analysis. RESULTS: A total of 430 patients were identified within the study period. Eighty-five percent of people (n = 365) achieved walking at the time of discharge (WISCI II level 12 = 260 and level 9 = 105). Out of 11 demographical and clinical parameters considered, eight of them were found to be significant predictors of walking in the univariate analysis. Age less than 30 years had the highest odds of predicting WISCI II level 9 and level 12 than those older in the multivariate analysis (OR 17.58; 95% CI 7.35-42.03). Single neurological level T12 increased the chance of achieving WISCI II level 12 by 10 times (OR 10.2; 95% CI 3.8-27.36). CONCLUSIONS: Orthotic walking for persons with motor complete low thoracic spinal cord injury is an achievable goal through a comprehensive rehabilitation program. The factors identified in this study will help rehabilitation professionals strategically select the ideal candidate for orthotic gait training.

Recalibration of the Framingham risk score for predicting 10-year risk of cardiovascular events: A non-concurrent rural cohort study from Tamil Nadu.

OBJECTIVE: To recalibrate the Framingham Risk Score-cardiovascular diseases (FRS-CVD) using 10-year mortality data and baseline risk factor data for a rural cohort and assess the effect of recalibration on proportion categorised as high risk. METHODS: Participants of a cardiovascular risk factor survey aged 30-64 years in 2011-12, from 9 villages of a rural block in Vellore, Tamil Nadu, were followed up for mortality till 2021, as part of an established demographic surveillance system. We calculated both lipid-based and Body Mass Index-based FRS-CVD risk scores, as well as recalibrated scores using risk factor data from the baseline survey and CVD mortality observed over 10 years. RESULTS: Based on original lipid-based FRS-CVD scores, 8.48% (109) of 1285 males had a 10-year CVD risk ≥30%, compared to 11.60% (149) with recalibrated scores. Among 1737 females, 1.50% (26) had a 10-year CVD risk of ≥30%, using original FRS-CVD scores, and 3.22% (56) using recalibrated scores. Similarly, for BMI based FRS-CVD scores, overall, 3.63% (110/3028) had a 10-year risk of ≥30%, compared to 6.64% (201) using recalibrated scores. The median 10-year FRS-CVD original score in males was 7.57 (IQR: 3.67-15.83), and 2.53 (IQR: 1.28-5.32) in females, compared to 8.95 (IQR: 4.35-18.52) and 3.79 (IQR: 1.92-7.93) respectively, for the recalibrated FRS-CVD risk scores. CONCLUSION: The recalibrated Framingham models showed a greater proportion of the population at risk of CVDs compared to the original FRS scores, with males having 2-3 times greater CVD risk scores compared to females.

Clinical features, outcomes and predictors of drug resistance and complications in patients admitted with pyelonephritis.

Drug resistance and the presence of structural complications have significant implications for the treatment of acute pyelonephritis. We aimed to examine the predictors of drug resistance and complications in a retrospective cohort of patients admitted with pyelonephritis. 188 patients were included in this study. Patients who had had a urinary catheterization in the previous month and who lived outside the district in which the hospital was located were more likely to have ESBL infections. Carbapenem resistance was associated with recent urinary catheterization, a positive urine nitrate test, hypotension requiring vasopressors and the need for intensive care. A history of flank pain, urea level >13.3 mmol/L, a differential neutrophil count >75% and a urinalysis with >1000 leucocytes per high power field was associated with an increased risk of complications. A score derived from these variables to predict structural complications of infection had a sensitivity of 77.8% and a specificity of 67.1.

The Clinical Profile and Long-Term Outcome of Children with Membranous Nephropathy, and the Evaluation of Anti-Phospholipase A2 Receptor Antibody Immunohistochemistry in Kidney Biopsy.

Introduction: Idiopathic membranous nephropathy (iMN) is a rare cause of nephrotic syndrome in children (1%-7%). Anti-phospholipase A2 receptor (PLA2R) antibody positivity in kidney biopsy is observed in 52%-78% of adults and 45% of children with iMN. The objectives of the study are to analyze the clinical profile and outcome of membranous nephropathy in children, to assess the prevalence of anti-PLA2R immunohistochemistry (IHC) in kidney biopsy, and to correlate their presence with disease characteristics. Methods: We are reporting a single-center retrospective study conducted in pediatric nephrology division. Clinical data and outcome parameters of children with membranous nephropathy were analyzed. PLA2R IHC was performed in kidney biopsy specimens retrospectively. Results: We analyzed 43 children with membranous nephropathy (MN) from a single center. 18 (42%) had idiopathic MN (iMN). PLA2R IHC was performed in kidney biopsy specimens in 14/18 (78%) patients with iMN and 7/9 (78%) non-lupus secondary membranous nephropathy (SMN) patients. The most common cause of SMN was lupus nephritis in 16 patients (64%). The mean estimated glomerular filtration rate (eGFR) at onset was 156 ± 81 ml/min/1.73m2. The sensitivity and specificity of PLA2R IHC in diagnosing pediatric MN was 50% and 57%, respectively; positive and negative predictive values were 70% and 36%, respectively. At the final follow-up, chronic kidney disease stage 5 (CKD 5) developed in 2/14 (14.3%) iMN patients. Conclusions: IHC PLA2R staining of glomerular tissue is a useful diagnostic marker of IMN. Though PLA2R prevalence is lower in children, its role in guiding treatment needs further exploration.

Pulmonary tuberculosis and diabetes mellitus: Clinical profile and outcomes.

Background: India is endemic for Tuberculosis (TB), contributing to the world's highest number of active cases. Diabetes (DM), with its increasing burden in India, could contribute to adverse outcomes among patients with TB. Methods: Consecutive patients with sputum smear positive pulmonary tuberculosis were included in the study. We defined cases as those patients with diabetes at recruitment. Controls were non diabetics (NDM). Sputum samples for AFB smears, AFB culture and Xpert PCR along with blood samples for glycosylated Haemoglobin and glucose levels were collected at recruitment and at 6 months from patients with sputum positive pulmonary TB. Blood glucose levels and sputum smears were repeated at 2 months and monthly till they tested negative. The primary outcome studied was mortality at 6 month follow-up. The secondary outcomes included the time to conversion of sputum smears and cure rates between cases and controls. Results: We recruited 124 patients of which 68 were cases. Mortality after therapy was 15% in cases and 7% in controls, however, the difference was not statistically significant. Equal proportions in each group (Diabetics: 9% vs. NDM 9%) had persistent smear positivity at 2 months. There was no association between delayed sputum conversion and uncontrolled diabetes. Only about 57% of cases and 50% of controls were documented to have completed treatment or been cured. A significant reduction in HbA1c after 6 months of Antituberculous therapy was noted among the cases. [Mean difference - 1.76, P-value - 0.001, 95% CI of difference - (1.01 - 2.52)]. Conclusions: Diabetes did not have adverse outcomes in the form of increased mortality or delayed sputum conversion rates. The high proportion of loss to follow-up seems to be a trend of concern, which should be addressed emergently.