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Background: Immunofluorescence (IFM) antigen mapping is the most commonly used technique to diagnose and differentiate epidermolysis bullosa (EB). In India, IFM is limited to few research laboratories and is not readily available, making the diagnosis largely clinical and often inaccurate. Ob jective of the Study: To examine the diagnostic usefulness of immunohistochemistry (IHC) as compared to IFM in resource-limited settings.Methods: Forty-four consecutive EB patients were included in this study. IHC and IFM were performed on 7-µm frozen tissue sections using standard laboratory protocols with a limited panel of antibodies. The kappa coefficient of agreement was calculated with genetic analysis as the gold standard.Results: IFM and IHC accurately identified the subtype of EB in 80.9% (p < 0.001) of the cases, when a clear blister cavity was evident on biopsy. The sensitivities and specificities of IHC and IFM for diagnosing EB simplex, junctional EB, and dystrophic EB were 100, 100, and 60% and 82.4, 100, and 100%, respectively. IHC was equally effective (p < 0.001) in establishing the type of EB as IFM.Conclusions: IHC staining and its interpretation were simple and comparable to IFM. IHC had an advantage of showing subtle changes in the epidermal architecture that could not be appreciated on IFM and hence can be considered useful in resource-limited settings. [ABSTRACT FROM AUTHOR]

Background: Active Pharmaceutical Ingredient (API) manufacturing is an important segment of the Indian pharma industry. India ranks third in terms of volume of medicines produced, and is a major global supplier of generic medicines. However, India depends heavily on the import of several raw materials used to produce some of these medicines. Main Body: This paper highlights how the situation emerged, as well as the various steps taken by the government to reduce import dependency and promote domestic manufacturing of APIs. Through various consultations with government officials, policy analysts and academicians, and interactions with key industry experts, the paper also highlights the public health perspectives of such dependence, especially regarding the secure access to essential medicines. India needs a conducive ecosystem to capitalize on the full potential of its API manufacturing capabilities, which may require some short-term and some mid/long-term interventions. Conclusions: It concludes by providing certain short-, medium- and long-term recommendations in the policy, fiscal and technology domains, to promote API independence. It also summarizes the various steps taken by the government in moving towards domestic manufacturing of APIs. [ABSTRACT FROM AUTHOR]

Objective: Acute kidney injury (AKI) is a frequent presentation in malaria infections. Several cases of AKI that are accompanied by clinical symptoms of malaria infection, such as fever, nausea, respiratory distress, and anemia remain undiagnosed due to challenges in accurate diagnosis using peripheral blood microscopy and rapid diagnostic tests that are currently used in clinical settings. This is particularly true for P. vivax and P. knowlesi infections. As a result, these patients are not able to receive anti-malarial therapy in a timely manner. The objective of the present study was to investigate if patients presenting with AKI harbored any of the five human Plasmodium species (P. falciparum, P. vivax, P. knowlesi, P. malariae, and P. ovale) within their renal tissues., Results: We found that renal biopsies from malaria associated AKI patients harbor the human malaria parasites P. falciparum, P. vivax and P. knowlesi as mono- and mixed species infections. Presence of microvascular injury in a majority of the malaria associated AKI cases suggested vascular involvement of P. vivax and P. knowlesi. This research note also highlights P. knowlesi as an emerging pathogen in the Indian subcontinent.

Introduction: BK polyomavirus is ubiquitous and remains dormant in the urothelial tract, reactivating and replicating in the immunocompromised state especially in the setting of post-renal transplantation where it is believed to be directly oncogenic based on recent reports. Its oncogenic role in the immunocompetent host is controversial. This study aimed to investigate the association of BK polyomavirus in Urothelial Carcinoma., Material and Methods: Patients with suspected urothelial carcinoma (UC) admitted under Department of Urology over a period of one year were recruited and transuretheral bladder tumor (TURBT) resection was performed, along with sampling of cystoscopically normal-appearing urothelium away from the tumor. In addition, cystectomy specimens with UC were included, with sampling of grossly normal-appearing urothelium away from the tumor. Immunohistochemistry (IHC) for SV40 T-Antigen and chromogenic in situ hybridization (CISH) using BK polyomavirus specific probe was performed on the paired samples (tumor and normal)., Results: Twenty-three TURBT and 14 cystectomy specimens were assessed. None of the cases showed evidence of BK polyomavirus infection in tumor or in surrounding mucosa by IHC. CISH performed in ten cases were also found to be negative. In comparison, one post-renal transplant urothelial carcinoma in our experience showed diffuse SV40 staining., Conclusions: This study suggests that BK polyomavirus infection is not associated with urothelial malignancy in the immunocompetent setting unlike in the immunocompromised setting where it should always be investigated for., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Infection with Plasmodium vivax, a common human parasite, is occasionally recognized to cause severe organ dysfunction similar to P. falciparum infection. Acute kidney injury (AKI) in malaria is attributed to acute tubular necrosis; thrombotic microangiopathy is not described., Methods: This observational study includes patients referred to a tertiary care center in North India during June to September 2011 with severe AKI, anemia, and thrombocytopenia following vivax malaria. Renal biopsies were processed by light, immunofluorescence, and electron microscopy., Results: Nine patients (including 5 children) had persistent AKI with thrombocytopenia and variable anemia following the diagnosis of malaria. Based on peripheral smear, eight patients were diagnosed with vivax malaria and had received antimalarial therapy prior to referral; a laboratory diagnosis of P. vivax infection was made for one patient at this center. Renal histology in all cases showed features of thrombotic microangiopathy, including fibrin thrombi, subendothelial widening, and mesangiolysis, along with variable tubulointerstitial nephritis and acute tubular or cortical necrosis. Ultrastructural examination confirmed endothelial injury and subendothelial widening. All patients required hemodialysis, and six were dialysis dependent at four weeks. Delayed presentation to the hospital (P = 0.019), hemolysis on peripheral smear (P = 0.083), and prolonged oligoanuria (P = 0.036) were associated with dialysis dependence., Conclusion: The association of anemia, thrombocytopenia, and renal histological evidence of thrombotic microangiopathy with vivax malaria is novel, and suggests the presence of severe endothelial injury. Further studies are necessary to confirm the association and examine the factors associated with its occurrence.

Focal and segmental glomerulosclerosis (FSGS) in renal allografts may occur as a recurrence of primary FSGS, as a de novo phenomenon or as a complication of calcineurin inhibitor toxicity. There are very few studies in the literature describing the clinico-pathologic characteristics of FSGS in renal allografts. To the best of our knowledge, no such study exists from the Indian subcontinent. Thirty-seven cases showing FSGS, of 426 transplant biopsies performed over a 4-year period (2006-2009), were included in this study. The pre- and post-transplant clinical data were noted. FSGS was classified as per the Columbia scheme. Appropriate statistical tests were applied. The age of the study patients ranged from 13 to 54 years, with a male preponderance. Thirty-five patients (94.6%) were diagnosed as FSGS more than 12 months after transplantation. All the patients presented with renal dysfunction (median serum creatinine 2.8 mg/dL) and detectable proteinuria at the time of diagnosis. Histologically, FSGS-NOS (70.3%) was observed as the most common subtype, followed by collapsing and perihilar varieties (13.5% each). Most of the biopsies (83.7%) showed grade-2 to -3 interstitial fibrosis and tubular atrophy. Follow-up data were available in 27 patients (73%), of whom 12 (44.4%) had graft loss with dialysis-dependent state at last follow-up. FSGS is one of the important causes of graft dysfunction, especially late in the post-transplantation period in cases of de novo FSGS. The long-term outcome of renal allografts developing this glomerular pathology is quite dismal, with a significant proportion of patients suffering graft loss.

Vascular changes in lupus nephritis (LN) may be the cause of renal function derangement without obvious changes in activity or chronicity indices. Although a few morphological studies of renal vasculature exist, arteriolar morphometric parameters in LN have not been evaluated. For this study, 40 patients with LN and 40 age-matched patients with minimal change disease (controls) were included. Their clinical features were noted, renal biopsy changes classified according to the modified World Health Organization classification of LN and activity and chronicity indices were calculated. Arteriolar morphometric parameters were obtained using manual tracing and an image analysis software. Appropriate statistical tests were applied to assess significance of difference between various groups. Arteriolar wall thickness as well as circumference was significantly higher in all classes of LN as compared with controls (P <0.05). However, no difference was observed in the wall-to-lumen ratio between the two groups (P >0.05). An inter-class analysis of LN did not show any significant difference for any of the arteriolar morphometric parameters (P >0.05). No correlation was found between activity or chronicity indices and the various arteriolar morphometric parameters. This study demonstrates morphometric evidence of arteriolar wall changes in LN. Although no correlation was found with the histological features, further studies are required in this area.

Objective: To review the disease course in patients with steroid sensitive nephrotic syndrome (SSNS) and the factors that determine outcome, Design: Retrospective, analytical, Setting: Pediatric Nephrology Clinic at referral center in North India, Participants/patients: All patients with SSNS evaluated between 1990 and 2005 INTERVENTION: None, Main Outcome Measures: Disease course, in patients with at least 1-yr follow up, was categorized as none or infrequent relapses (IFR), frequent relapses or steroid dependence (FR), and late resistance. Details on complications and therapy with alternative agents were recorded., Results: Records of 2603 patients (74.8% boys) were reviewed. The mean age at onset of illness and at evaluation was 49.7±34.6 and 67.5±37.9 months respectively. The disease course at 1-yr (n=1071) was categorized as IFR in 37.4%, FR in 56.8% and late resistance in 5.9%. During follow up, 224 patients had 249 episodes of serious infections. Alternative medications for frequent relapses (n=501; 46.8%) were chiefly cyclophosphamide and levamisole. Compared to IFR, patients with FR were younger (54.9±36.0 vs. 43.3±31.4 months), fewer had received adequate (=8 weeks) initial treatment (86.8% vs. 81.7%) and had shorter initial remission (7.5±8.6 vs. 3.1±4.8 months) (all P<0.001). At follow up of 56.0±42.6 months, 77.3% patients were in remission or had IFR, and 17.3% had FR., Conclusions: A high proportion of patients with SSNS show frequent relapses, risk factors for which were an early age at onset, inadequate initial therapy and an early relapse.