Use of thiopurines in inflammatory bowel disease : an update

Inflammatory bowel disease (IBD), once considered a disease of the Western hemisphere, has emerged as a global disease. As the disease prevalence is on a steady rise, management of IBD has come under the spotlight. 5-Aminosalicylates, corticosteroids, immunosuppressive agents and biologics are the backbone of treatment of IBD. With the advent of biologics and small molecules, the need for surgery and hospitalization has decreased. However, economic viability and acceptability is an important determinant of local prescription patterns. Nearly one-third of the patients in West receive biologics as the first/initial therapy. The scenario is different in developing countries where biologics are used only in a small proportion of patients with IBD. Increased risk of reactivation of tuberculosis and high cost of the therapy are limitations to their use. Thiopurines hence become critical for optimal management of patients with IBD in these regions. However, approximately one-third of patients are intolerant or develop adverse effects with their use. This has led to suboptimal use of thiopurines in clinical practice. This review article discusses the clinical aspects of thiopurine use in patients with IBD with the aim of optimizing their use to full therapeutic potential.Peer reviewe

Liver pathology in collagen vascular disorders highlighting the vascular changes within portal tracts

Background: Collagen vascular disorders (CVDs) are autoimmune disorders with multisystem involvement. Clinical liver involvement is not a characteristic feature though histological involvement could be frequent. Liver disease in CVDs could be the consequence of various factors. Aim: The aim was to analyze the histological spectrum of liver in collagen vascular disorders (CVDs) at autopsy. Materials and Methods: Thirty-six autopsy livers negative for hepatitis B or C virus were studied in CVD cases with no known association with chronic liver disease or vascular thrombosis or hematological disorder. Cirrhotic and normal livers were used as controls. The paired t-test, one-way ANOVA, and two-sided Dunnett t-test were used for comparison (0.05). Most SLE cases had increased transaminases (P<0.05). No evidence of portal hypertension was seen in all except in one RA. Septicemia is known to be associated with raised transaminases. Conclusion: A rare pathology of conglomerate of abnormal vessels in intermediate- and small-sized portal system was observed co-existing with NRHL in CVDs. Raised liver enzyme with interface hepatitis in CVD may not necessarily warrant an overlap, as a similar feature could be observed in septicemia

ALK+ Anaplastic large cell lymphoma with extensive cardiac involvement: A rare case report and review of the literature

Cardiac lymphoma is a rare entity. In this setting, the secondary involvement of the heart is far more frequent than the primary cardiac lymphoma. Herein, we present an autopsy case of a disseminated anaplastic lymphoma kinase (ALK)- positive anaplastic large cell lymphoma with a dominant mediastinal involvement. Extensive cardiac infiltration with the near replacement of the myocardial wall by the neoplastic cells was observed. A total of nine isolated case reports of anaplastic large cell lymphoma with cardiac involvement were found in the English-language literature, and a widespread cardiac and thymic infiltration by the systemic ALK-positive anaplastic large cell lymphoma has not been documented. An incidental regenerative nodule was also identified in the liver. The patient died of pulmonary thromboembolism and cardiac arrest

Computed Tomography Findings in Intraabdominal Hypertension in Patients with Acute Pancreatitis

Purpose Intraabdominal hypertension (IAH) in acute pancreatitis (AP) may reduce tissue perfusion and impair organ function and has been shown to portend poor prognosis. We investigated the computed tomography (CT) findings in patients with AP with IAH. Methods This retrospective study comprised of consecutive patients with AP from June 2016 to June 2018 in whom intraabdominal pressure (IAP) was measured. The patients who underwent a contrast-enhanced CT within 7 days of IAP measurement were included. Using a cutoff of 12 mm Hg for IAP, the patients were divided into IAH and non-IAH groups. Measures of severity and clinical outcome were evaluated. CT parameters were compared between the groups. Results The IAH group comprised of 41 patients, while there were 20 patients in the non-IAH group. The IAH group was characterized by severe disease, increased incidence of organ failure, increased requirement for drainage and surgery, prolonged hospital and intensive care unit stay. The mortality was not significantly different between the two groups. On univariate analysis, the CT features that were found to be significantly different between the two groups were the presence of collection (p = 0.036), the maximum dimension of collection (p = 0.004), volume of collection (p = 0.019), biliary dilatation (p = 0.011), and the presence of moderate-to-severe pleural effusion (p = 0.009). On multivariate analysis, all these parameters except biliary dilatation were found to be statistically significant. Conclusion CT findings in patients with AP may suggest IAH. This can be used as an additional marker for severity of AP

Multiplex PCR for rapid diagnosis of gastrointestinal tuberculosis

Background: Rapid and specific diagnosis of gastrointestinal tuberculosis (GITB) is of utmost importance. Aim: To evaluate Multiplex PCR (MPCR) using MPB64 and IS6110 primers specific for M. tuberculosis for rapid diagnosis of GITB. Materials and Methods: MPCR was performed on colonoscopy biopsy specimens on 11 GITB confirmed (culture/AFB/histopathology was positive), 29 GITB suspected and 30 Non GITB (control group) patients. Results: MPB64 PCR had sensitivity and specificity of 90% and 100% for confirmed GITB cases. In 29 clinically diagnosed but unconfirmed GITB cases, MPCR was positive in 72.41%. MPCR was negative in all control group patients. The overall sensitivity and specificity of microscopy, culture, histopathology and MPCR was 5%, 2% 20% and 77.5% and 100%, 100%, 100% and 100% respectively. Conclusion: MPCR has good sensitivity and specificity in diagnosing gastrointestinal tuberculosis

A Combined Gene Signature of Hypoxia and Notch Pathway in Human Glioblastoma and Its Prognostic Relevance

<div><p>Hypoxia is a hallmark of solid tumors including glioblastoma (GBM). Its synergism with Notch signaling promotes progression in different cancers. However, Notch signaling exhibits pleiotropic roles and the existing literature lacks a comprehensive understanding of its perturbations under hypoxia in GBM with respect to all components of the pathway. We identified the key molecular cluster(s) characteristic of the Notch pathway response in hypoxic GBM tumors and gliomaspheres. Expression of Notch and hypoxia genes was evaluated in primary human GBM tissues by q-PCR. Clustering and statistical analyses were applied to identify the combination of hypoxia markers correlated with upregulated Notch pathway components. We found well-segregated tumor—clusters representing high and low HIF-1α/PGK1-expressors which accounted for differential expression of Notch signaling genes. In combination, a five-hypoxia marker set (HIF-1α/PGK1/VEGF/CA9/OPN) was determined as the best predictor for induction of Notch1/Dll1/Hes1/Hes6/Hey1/Hey2. Similar Notch-axis genes were activated in gliomaspheres, but not monolayer cultures, under moderate/severe hypoxia (2%/0.2% O₂). Preliminary evidence suggested inverse correlation between patient survival and increased expression of constituents of the hypoxia-Notch gene signature. Together, our findings delineated the Notch-axis maximally associated with hypoxia in resected GBM, which might be prognostically relevant. Its upregulation in hypoxia-exposed gliomaspheres signify them as a better <i>in-vitro</i> model for studying hypoxia-Notch interactions than monolayer cultures.</p></div