Long-term safety and effectiveness of azathioprine in the management of inflammatory bowel disease: A real-world experience.

Background and Aim: Azathioprine (AZA) forms the cornerstone for maintenance of sustained remission in inflammatory bowel disease (IBD). There is apprehension regarding the long-term effectiveness and safety of AZA in IBD. We present our experience with AZA use and outcomes in a cohort of IBD patients followed up over a long period of time. Methods: Records of 507 IBD patients under treatment at a single, tertiary care center in south India between 2013 and 2022 were evaluated retrospectively. Long-term compliance, tolerance, clinical outcome at the point of last follow-up, type and duration to the onset of adverse events, and subsequent amendment to treatment with regard to AZA were analyzed. Results: Of 507 patients with IBD, 320 patients (207 Crohn's disease [CD], 113 ulcerative colitis [UC]) who received AZA were included. The median follow-up was 41 months (interquartile range 15.5-77.5). Total duration of exposure was 1359 patient-years with median usage of 33 months. Of the patients, 26.9% received AZA for >5 years. Mean initiation and maximum doses of AZA were 0.97 and 1.72 mg/kg/day. Among the participants, 20.6% experienced side effects, including myelotoxicity (7.2%) and gastrointestinal intolerance (5.6%). Six patients developed malignancy. Among the side effects, 39.4% of side effects were dose-dependent. Among the patients, 38.1% had relapses requiring pulse corticosteroid therapy, and 16.2% had more than one relapse after commencement of AZA. AZA was continued till the last follow-up in 76.5%. Among the patients, 49.7% (UC 51.3, CD 48.8) attained durable remission without biologics, and 5.3% continued to have active disease. Conclusion: AZA is safe and effective in the long-term in IBD. Effectiveness, tolerance, and compliance with AZA are well sustained beyond 5 years of usage and comparable between UC and CD.

Urine neutrophil gelatinase-associated lipocalin as a biomarker of acute kidney injury and prognosis in decompensated chronic liver disease: A prospective study.

BACKGROUND: Acute kidney injury (AKI) heralds deterioration in patients with decompensated chronic liver disease (DCLD). Serum creatinine (sCr), a component of the model for end-stage liver disease-sodium (MELD-Na) prognostic score, has limitations in patients with DCLD. We evaluated the prognostic role of urine neutrophil gelatinase-associated lipocalin (NGAL) in DCLD and its ability to sub-type AKI. METHODS: Total 147 consecutive patients hospitalized between June 2018 and June 2020 for complications of DCLD were evaluated. Urine NGAL was estimated and demographic, clinical and biochemical parameters recorded at baseline. Participants were followed up till the end of study period or mortality, whichever came earlier. Primary outcomes included all-cause mortality and time to death after index hospitalization. Secondary outcomes included the presence and type of AKI, need for intensive care unit (ICU) stay, length of ICU/hospital stay, in-hospital mortality, development of new-onset/recurrent AKI and recurrent hospitalization after index admission. RESULTS: Urine NGAL was highest in acute tubular necrosis (ATN), lowest in pre-renal azotemia (PRA) and intermediate in hepatorenal syndrome (HRS-AKI). Urine NGAL (p = 0.0208) was superior to sCr (p = 0.0388) and inferior to fractionated excretion of sodium (FENa) (p = 0.0013) in stratifying AKI. A cut-off of 203.9 ng/mL discriminated between HRS and PRA with sensitivity 77.8% and specificity 68.7%. Urine NGAL correlated with MELD-Na score, need for ICU stay, in-hospital mortality and mortality at three and six months. Two-year survival was significantly lower in patients with urine NGAL > 205 ng/mL. Addition of log-urine-NGAL score did not improve predictive performance of MELD-Na. CONCLUSION: Urine NGAL could identify AKI sub-types and correlated with short-term clinical outcomes, including mortality.

Novel biomarkers of acute kidney injury in chronic liver disease: Where do we stand after a decade of research?

Acute kidney injury (AKI) is a frequently encountered complication in decompensated chronic liver disease (CLD) with an estimated prevalence of 20%-50% among hospitalized patients. AKI often heralds the onset of a downhill course in the natural history of CLD. Serum creatinine has several limitations as a stand-alone marker of AKI in patients with decompensated CLD. The concept of hepatorenal syndrome, the prototype of AKI in decompensated CLD, has evolved tremendously over recent years. There is emerging evidence of an additional "structural" component in the pathophysiology of hepatorenal syndrome-AKI, which was previously identified as a purely "functional" form of renal impairment. Lacunae in the existent biochemical arsenal for diagnosis and prognosis of AKI have fueled enthusiastic research in the field of novel biomarkers of kidney injury in patients with cirrhosis. The advent of these biomarkers provides a crucial window of opportunity to improve the diagnosis and clinical outcomes of this vulnerable cohort of patients. This review summarizes the dynamic concept of renal dysfunction in CLD and the available literature on the role of novel biomarkers of AKI in assessing renal function, identifying AKI subtypes, and predicting prognosis. There is special emphasis on the renal tubular injury marker, neutrophil gelatinase-associated lipocalin, the most exhaustively studied biomarker of AKI in the CLD population.

Inflammatory bowel diseases in Tamil Nadu: A survey of demographics, clinical profile, and practices.

BACKGROUND: Inflammatory bowel disease (IBD) is increasingly diagnosed in South Asia. This survey by the Tamil Nadu Chapter of the Indian Society of Gastroenterology (TNISG) documents the demography, clinical profile, and therapeutic practices related to IBD in Tamil Nadu. METHODS: TNISG members from 32 institutions completed an online cross-sectional questionnaire on IBD patients from March 2020 to January 2021. RESULTS: Of 1295 adult IBD patients, 654 had Crohn's disease (CD), 499 ulcerative colitis (UC), and 42 IBD-unclassified (IBD-U). CD and UC showed a unimodal age distribution. A total of 55% were graduates or postgraduates. A positive family history was noted in 30, other risk factors were uncommon. In CD, the pattern of involvement was ileocolonic (42.8%), ileal (34.7%), colonic (18.9%), and upper gastrointestinal (3.5%); while in UC, disease was characterized as extensive (44.9%), left-sided (41.7%), or proctitis (13.4%). Perineal disease, perianal fistulae, and bowel obstruction were noted in 4.3, 14.0, and 23.5%, respectively, of CD. The most widely used drugs were mesalamine, azathioprine, and corticosteroids. Surgery was undertaken in 141 patients with CD and 23 patients with UC. Of the 138 patients with pediatric IBD (≤16 years), 23 were characterized as very early onset IBD (VEO-IBD), 27 as early-onset, and 88 as adolescent IBD. VEO-IBD were more likely to have a positive family history of IBD and were more likely to have perineal disease and to have the IBD-U phenotype. Among pediatric IBD patients, corticosteroids, mesalamine, and azathioprine were the most commonly used medications, while 25 pediatric patients received biologics. CONCLUSION: This study provides important information on demography, clinical profile, and treatment practices of IBD in India.

Pancreatic Adenocarcinoma With Synchronous Colonic Metastases.

Metastases from pancreatic malignancy are commonly known to occur in the regional lymph nodes, liver, lung, and peritoneum. Synchronous or metachronous metastasis from the pancreas to the colon is rare, with only 6 cases reported in the literature. We report a man who was found to have adenocarcinoma on biopsies from synchronous lesions in the colon and the pancreas. The immunohistochemistry report revealed the diagnosis of a primary pancreatic malignancy with synchronous colonic metastases.

Gastric IgG4-related disease presenting as a mass lesion and masquerading as a gastrointestinal stromal tumor.

IgG4-related disease of the stomach is a rare disorder, and only a few cases have been reported. We present two cases that were identified over a 2-month period in our center. Two male patients aged 52 and 48 years presented with mass lesion in the stomach, which were clinically thought to be gastrointestinal stromal tumor, and they underwent excision of the lesion. Microscopic examination revealed marked fibrosis, which was storiform in one case, associated with diffuse lymphoplasmacytic infiltration and an increase in IgG4-positive plasma cells on immunohistochemistry. Serum IgG4 level was markedly elevated. Although rare, IgG4-related disease should be considered in the differential diagnosis of gastric submucosal mass lesions.