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.

Computed tomography features predictive of intra-abdominal hypertension in acute necrotizing pancreatitis: A prospective study.

BACKGROUND: Intra-abdominal hypertension (IAH) and abdominal compartment syndrome (ACS) in acute pancreatitis (AP) are associated with development and worsening of organ failures and poor prognosis. Limited studies suggest that contrast-enhanced computed tomography (CECT) can predict the presence of IAH/ACS. We aimed to study clinical profile of patients with AP and IAH and identify predictive factors of IAH on CECT abdomen. METHODS: Consecutive patients admitted with moderately severe and severe acute pancreatitis (SAP) were recruited. Clinical and radiological data were recorded prospectively. Intra-abdominal pressure was measured via a urinary catheter to document the presence of IAH/ACS. CECT abdomen was done within the first week of admission and various features that may predict the presence of IAH were studied. RESULTS: Thirty-seven patients (24 SAP) (mean age: 39.78 ± 13.43 years and 67.6% males) with  AP were studied. The most common etiology was alcohol (37.7%). IAH developed in 54.05% of patients; patients with IAH had significantly higher bedside index of severity in AP (BISAP), Acute Physiologic Assessment and Chronic Health Evaluation II (APACHE II) score, persistent acute lung injury (ALI), persistent acute kidney injury (AKI), persistent cardiovascular failure (CVSF), intensive care unit (ICU) stay, and mortality. Among the CT predictors, patients with IAH more commonly had moderate-gross ascites (60% vs. 23.5%, p-value - 0.026), a pancreatic necrosis of > 50% (50% vs. 17.6%, p-value - 0.04), and a round belly sign (RBS) (50% vs. 5.9%, p-value 0.03). On multivariate analysis, only RBS was predictive of  IAH (odds ratio 12.6, 95% confidence interval 1.3-124.2, p-value 0.03). The sensitivity, specificity, positive predictive value, and negative predictive value for RBS were 50%, 94.12%, 90.9%, and 61.54%, respectively. CONCLUSION: Presence of RBS, moderate-gross ascites, and pancreatic necrosis of > 50% on CECT can predict the presence of IAH in these groups of patients.

Serial measurements of faecal calprotectin may discriminate intestinal tuberculosis and Crohn's disease in patients started on antitubercular therapy.

BACKGROUND: Response to antitubercular therapy (ATT) is often used to differentiate intestinal tuberculosis (ITB) from Crohn's disease. Role of non-invasive biomarkers to predict mucosal response to ATT is unclear. MATERIALS AND METHODS: A prospective study to compare faecal calprotectin and serum C-reactive protein (CRP) levels at diagnosis, 2 and 6 months of ATT in patients with suspected ITB started on ATT was done. The patients were eventually divided into two groups: ITB or alternative diagnosis (OTH). Decline of calprotectin and CRP levels was used to compute area under the receiver operating characteristic (AUROC) to predict mucosal healing at 2 months. RESULTS: Thirty-seven patients (mean age: 34.95 ± 16.35 years, 23 males) were included and 28 (75.67%) were diagnosed as ITB while nine (24.32%) had alternative diagnosis (OTH). The median faecal calprotectin values of ITB and OTH groups at baseline, 2 months and 6 months were 216 and 282 µg/g (P = 0.466), 43 and 216 µg/g (P = 0.003), and 26 and 213 µg/g (P < 0.001), respectively. The median CRP values at baseline, 2 months and 6 months were 18 and 30 mg/L (P = 0.767), 4.7 and 15 mg/L (P = 0.025), and 3 and 10.85 mg/L (P = 0.068), respectively. The AUROC of percent decline in faecal calprotectin and serum CRP at 2 months for mucosal healing were 0.8287 [95% confidence inteval (CI) 0.6472-1] and 0.6018 (95% CI 0.4079-0.7957), respectively. CONCLUSION: Faecal calprotectin can help in assessing response to therapy in suspected ITB patients started on empirical ATT.

Comparison of endoscopic versus percutaneous drainage of symptomatic pancreatic necrosis in the early (< 4 weeks) phase of illness.

BACKGROUND AND OBJECTIVE: Pancreatic fluid collections in early phase of illness <4 weeks after onset of acute pancreatitis (AP) are usually treated with percutaneous drainage (PCD). There is a paucity of data comparing early (<4 weeks) endoscopic transluminal drainage (ETD) with PCD in patients with symptomatic pancreatic necrosis (PN). The objective of this study is to compare the safety and efficacy of early ETD with PCD in patients with symptomatic PN. PATIENTS AND METHODS: Retrospective analysis of database of patients with symptomatic PN treated early (<4 weeks of onset of AP) with either ETD (encapsulated wall on EUS) or PCD. RESULTS: Twenty-three patients (19 M; mean age: 36.1 years) were treated with ETD and 41 patients (29 M; mean age: 39.6 years) were treated with PCD, respectively. ETD and PCD were done 24.2 ± 2.3 and 24.2 ± 2.0 days after onset of AP, respectively (P = 0.84). In the ETD group, 35% of patients were treated with self-expanding metallic stents and 48% of patients required direct endoscopic necrosectomy. In the PCD group, 74% of patients were treated with multiple catheters and 91% of patients with either saline or streptokinase irrigation. As compared to the ETD group, patients in the PCD group took longer time for resolution (61.9 ± 22.9 days vs. 30.9 ± 5.6 days; P < 0.00001), increased need for surgery (30% vs. 4%; P = 0.01), and frequency of formation of external pancreatic fistula (EPF) (22% vs. nil; P = 0.02). CONCLUSIONS: ETD of PN in early phase of illness is associated with a shorter duration for resolution and infrequent need of salvage surgery compared to PCD. EPF formation is a significant adverse event with PCD.

Appropriate chemopreventive strategy for anti-tubercular therapy related liver injury is unsettled: Results from a systematic review and network meta-analysis.

BACKGROUND: Role of chemoprophylaxis for prevention of antitubercular therapy-related drug-induced liver injury (ATT-DILI) is uncertain. METHODS: Electronic databases were searched for randomized trials reporting on chemoprophylaxis agents for prevention of ATT-DILI. We included studies evaluating the role of a drug in comparison to controls/placebo. The primary outcome was the occurrence of ATT-DILI. We performed a Bayesian random-effects network meta-analysis to calculate odds ratios (ORs) and 95% credible intervals (CrI) for those arms where at least two studies were available. Additional comparative studies for these arms were also identified. RESULTS: Fourteen studies were identified and seven included in the meta-analysis. The agents used for prevention of ATT-DILI were silymarin/silibinin (4 trials), N-acetylcysteine (NAC) (3 studies), herbal preparations (5 studies) and one study each for cholecalciferol and carnitine. Compared with controls/placebo, the odds of occurrence of hepatotoxicity with NAC was 7 * 10-17 (95% CrI: 2.8 * 10-53, 0.0053) and Silymarin was 0.68 (95% CrI: 0.084, 4.6). NAC had the highest probability of rank 1 (0.99) which was followed by Silymarin (0.004). CONCLUSION: N-acetyl cysteine, but not Silymarin/Silibinin, appears to be beneficial in prevention of ATT-DILI. However, the results were limited by the possible risk of bias in included studies, variable definitions of ATT-DILI and limited number and category of patients.

Disconnected pancreatic duct syndrome: Updated review on clinical implications and management.

Disconnected Pancreatic Duct Syndrome (DPDS) is an important but often overlooked complication of acute necrotising pancreatitis (ANP) that occurs due to necrosis of the main pancreatic duct (PD). This segmental necrosis leads on to disconnection between the viable upstream pancreatic parenchyma and the duodenum. The disconnected and functional segment of pancreas continues to secrete pancreatic juice that is not drained into the gastrointestinal tract and lead on to recurrent pancreatic fluid collections (PFC), refractory external pancreatic flstulae and chronic abdominal pain/recurrent pancreatitis. Because of lack of awareness of this important complication of ANP, the diagnosis of DPDS is usually delayed. The delay in diagnosis increases the morbidity of the disease as well as increase the cost of treatment and duration of hospital stay. Surgery has remained the cornerstone for management of patients with DPDS. The conventional surgical approaches have been either resection or internal drainage procedures. Surgery for DPDS in the setting of ANP is often difficult due to presence of local inflammation and extensive venous collaterals in the operative field due to splenic vein thrombosis and therefore is associated with significant morbidity. Advancement in therapeutic endoscopy, especially advent of therapeutic endoscopic ultrasound has opened an exciting new field of minimally invasive therapeutic options for management of DPDS. The present review discusses the current understanding of the clinical manifestations, imaging features and management strategies in patients with DPDS.