Intravenous albumin infusion does not augment the response rate to a combination of exclusive enteral nutrition and intravenous steroids in acute severe ulcerative colitis: a randomized controlled trial.

INTRODUCTION: 30-40% patients with acute severe ulcerative colitis (ASUC) fail intravenous (IV) steroids requiring medical rescue therapy/colectomy. Low baseline albumin predicts steroid non-response, and exclusive enteral nutrition (EEN) has been shown to improve steroid response and albumin levels. Albumin infusion due to its anti-inflammatory and anti-oxidant properties might further improve steroid response in ASUC, which was evaluated in present study. METHODS: In this open-label randomized controlled trial, patients with ASUC were randomized in 1:1 ratio to albumin + standard of care (SOC) + EEN vs. SOC + EEN (Jan2021 - Feb2023). Both arms received 5 days of EEN with 400 mg IV hydrocortisone/day. Patients in albumin arm were administered 5 days of 20% w/v intravenous albumin (100 ml). Primary outcome was 1) steroid failure (need for rescue medical therapy or colectomy) and 2) proportion of patients with adverse events. RESULTS: Sixty-one patients (albumin-30, SOC-31)(mean age-31.6±0.4 years, male-57.4%), were included. Baseline characteristics were comparable. There was no difference in steroid failure between albumin and SOC arm(10/30(33.33 %) vs 13/31(41.94 %), p=0.49). No adverse events were reported with albumin infusions. Colectomy rate(10% vs 9.68%, P=1), response to salvage medical therapy (88.89% vs 76.92%, P=0.62) and median duration of hospitalization (10.5(7-16) vs 10(7-20), P=0.43) were also comparable. Long-term composite outcome of colectomy and re-admission rates was numerically higher in the albumin than SOC arm (37.04% vs 17.86%, p>0.05), although it did not reach statistical significance. CONCLUSION: There was no benefit of intravenous albumin infusion as an adjunct to IV steroids and EEN in patients with ASUC.

Thiopurines Have Sustained Long-term Effectiveness in Patients with Inflammatory Bowel Disease, Which is Independent of Disease Duration at Initiation: A Propensity Score Matched Analysis.

BACKGROUND AND AIMS: Thiopurines are viable option for the treatment of inflammatory bowel disease [IBD] in resource-limited countries. However, data on the effect of disease duration at thiopurines initiation on long-term effectiveness are limited. METHOD: We performed a propensity matched analysis of a retrospective cohort of patients with ulcerative colitis [UC] and Crohn's disease [CD]. Patients initiated on thiopurines early in the disease course [≤2 years] were compared with those started late [>2 years]. Effectiveness was defined as no requirement for hospitalisation, anti-tumour necrosis factor [TNF] agents, or surgery, and minimum steroid requirement [≤1 steroid course in 2 years] during follow-up. RESULTS: A total of 988 [UC: 720, CD: 268] patients were included (male: 665 [60.8%], median age: 40 [32-51] years, median follow-up: 40 [19-81] months). Overall effectiveness at 5 and 10 years was 79% and 72% in UC, and 69% and 63% in CD, respectively. After propensity score matching, there was no difference in 5- and 10-year effectiveness between early and late thiopurine initiation groups either for UC [81% and 80% vs 82% and 74%; p = 0.92] or CD [76% and 66% vs 72% and 51%, p = 0.32]. Male sex for UC (negative: hazard ratio [HR]: 0.67, 95% confidence interval [CI): 0.45-0.97; p = 0.03), and ileal involvement [positive: HR: 3.03, 95% CI: 1.32-6.71; p = 0.008], steroid-dependent disease [positive: HR: 2.70, 95% CI: 1.26-5.68; p = 0.01] and adverse events [negative: HR: 0.47, 95% CI:0.27-0.80; p = 0.005] for CD were predictors of thiopurine effectiveness. CONCLUSION: Thiopurines have sustained long-term effectiveness in both UC and CD. However, early thiopurine initiation had no better effect on long-term disease outcome compared with late initiation.

Serum albumin is the strongest predictor of anti-tumor necrosis factor nonresponse in inflammatory bowel disease in resource-constrained regions lacking therapeutic drug monitoring.

BACKGROUND/AIMS: Evidence on predictors of primary nonresponse (PNR), and secondary loss of response (SLR) to anti-tumor necrosis factor (anti-TNF) agents in inflammatory bowel disease is scarce from Asia. We evaluated clinical/biochemical/molecular markers of PNR/SLR in ulcerative colitis (UC) and Crohn's disease (CD). METHODS: Inflammatory bowel disease patients treated with anti-TNF agents (January 2005-October 2020) were ambispectively included. Data concerning clinical and biochemical predictors was retrieved from a prospectively maintained database. Immunohistochemistry for expression of oncostatin M (OSM), OSM receptor (OSM-R), and interleukin-7 receptor (IL-7R) were done on pre anti-TNF initiation mucosal biopsies. RESULTS: One-hundred eighty-six patients (118 CD, 68 UC: mean age, 34.1±13.7 years; median disease duration at anti-TNF initiation, 60 months; interquartile range, 28-100.5 months) were included. PNR was seen in 17% and 26.5% and SLR in 47% and 28% CD and UC patients, respectively. In CD, predictors of PNR were low albumin (P<0.001), postoperative recurrence (P=0.001) and high IL-7R expression (P<0.027) on univariate; and low albumin alone (hazard ratio [HR], 0.09; 95% confidence interval [CI], 0.03-0.28; P<0.001) on multivariate analysis respectively. Low albumin (HR, 0.31; 95% CI, 0.15-0.62; P=0.001) also predicted SLR. In UC, predictors of PNR were low albumin (P<0.001), and high C-reactive protein (P<0.001), OSM (P<0.04) and OSM-R (P=0.07) stromal expression on univariate; and low albumin alone (HR, 0.11; 95% CI, 0.03-0.39; P=0.001) on multivariate analysis respectively. CONCLUSIONS: Low serum albumin at baseline significantly predicted PNR in UC and PNR/SLR in CD patients. Mucosal markers of PNR were high stromal OSM/OSM-R in UC and high IL-7R in CD patients.

Incidence and Predictors of Liver-Related Events in Patients With Nonalcoholic Fatty Liver Disease.

Background: Nonalcoholic fatty liver disease (NAFLD) is the commonest type of liver disease worldwide. We aimed to assess the incidence and predictors of liver-related events (LREs) and mortality in NAFLD patients. Methods: NAFLD patients (n = 957) evaluated between January 2000 and November 2021 were included. Patients were categorised as noncirrhosis (NC), compensated cirrhosis (CC) and decompensated cirrhosis (DC), and the incidence of LRE and mortality were estimated and compared. Results: The proportions of NC, CC and DC were 87.8% (n = 840), 8.8% (n = 84) and 3.4% (n = 33), respectively. The median follow-up duration was 3.9 (3.0-5.7) years, and the total cumulative duration was 4633 person-years. The incidence of LRE per 100 person-years was 0.14, 2.72 and 10.24 in patients with NC, CC and DC, respectively. The incidence of mortality was 0.12, 1.05 and 4.24 per 100 person-years, respectively, in the 3 groups. The causes of mortality in the 3 groups were liver related in 1/5 (20%), 3/4 (75%) and 6/9 (66.7%), respectively. Overall, the mortality rate was higher in those with diabetes than those without diabetes (log-rank P value = 0.005). On further analysis, diabetes was associated with poor outcomes only in NC group (log-rank P value = 0.036), and not in CC (log-rank P value = 0.353) or DC groups (log-rank P value = 0.771). On multivariate Cox proportional hazard analysis, age (hazard ratio [HR] 1.070), hypertension (HR 4.361) and DC (HR 15.036) were independent predictors of poor outcomes. Liver stiffness measurement, bilirubin, CC and DC were independent predictors of LRE. Conclusion: In our study of NAFLD from India, the incidence of LRE was found to be similar to that seen in Western studies. In NC NAFLD, diabetes was associated with poor outcomes.

Efficacy and safety of biosimilar versus originator infliximab in patients with inflammatory bowel disease: A real-world cohort analysis.

BACKGROUND: Anti-tumor necrosis factor (anti-TNF) monoclonal antibody, infliximab, is the primary therapeutic modality for patients with Crohn's disease (CD) and ulcerative colitis (UC), refractory to conventional therapy. Biosimilars of infliximab have been shown to have equivalent efficacy to originator infliximab. We compared the safety and efficacy of infliximab biosimilar with the originator in Indian patients with inflammatory bowel disease (IBD). METHODS: Patients with IBD treated with either originator or biosimilar infliximab from January 2005 to October 2020 were included in this retrospective analysis. The safety and efficacy of originator or biosimilar infliximab in inducing and maintaining clinical remission at weeks 14 and 52 for CD and UC were evaluated. Disease activity was estimated at baseline, after induction therapy, after 1 year of treatment, and during 12 months of follow-up. RESULTS: In all, 137 patients (82 CD; 55 UC) were included, of whom 102 were on originator, and 35 patients received biosimilar. In biosimilar group, clinical response and remission rates at weeks 14 and 52 were 84.2%, 58% and 68.4%, 52.6% in CD and 81.2%, 56.2% and 68.7%, 62.5% in UC patients, respectively. Among patients who were on originator, clinical response and remission rates at weeks 14 and 52 were 79.4%, 46% and 57.1%, 43% in CD and 72%, 64.1% and 66.7%, 56.4% in UC patients, respectively. Thirty-three (24.1%) patients experienced adverse events; eighteen developed tuberculosis (TB), of whom 17 received originator and one patient received biosimilar. CONCLUSIONS: Infliximab biosimilar is comparable to originator infliximab in terms of safety profile and its efficacy in inducing and maintaining remission in patients with IBD.

Relapse rates after withdrawal of thiopurines in patients with inflammatory bowel disease.

PURPOSE: Withdrawal of thiopurines after remission is associated with an increased risk of relapse in patients with inflammatory bowel disease (IBD). However, long-term data on thiopurine withdrawal is limited, especially from developing countries where the cost of long-term therapy poses a significant burden on patients. METHODS: Patients with IBD on thiopurine monotherapy for ≥ 4 months, who stopped thiopurines while in clinical remission and were not on any other immunomodulator or biologics at the time of withdrawal, were included in this retrospective analysis. RESULTS: Among 1093 patients with IBD on thiopurine monotherapy, 461 patients stopped thiopurine due to various reasons. Among these, 218 (ulcerative colitis (UC) = 179; Crohn's disease (CD) = 39) patients were in clinical remission and were continued on mesalamine. Overall, 36.7% (n = 80) relapsed after a median duration of 20 months (IQR: 9-49). Relapse rate was higher in UC than CD (39.7% vs 23%, p = 0.055). Cumulative probabilities of relapse were 17%, 34%, and 44% at the end of 1, 3, and 5 years, respectively. The relapse rate at 5 years was significantly lower in patients who had stopped azathioprine after 4 years of therapy (31% vs 54%, p = 0.007). On multi-variate cox regression analysis, male sex [HR: 1.6(1.0-2.6), p = 0.02] and short duration of therapy with thiopurines [HR: 1.02 (1.01-1.02), p = 0.004] before withdrawal were associated with increased risk of relapse. CONCLUSION: Approximately 50% patients with IBD in remission would relapse after 5 years of thiopurine withdrawal. Male sex and shorter treatment duration predict relapse. Treatment should be continued in patients who tolerate and maintain remission on long-term thiopurine.

Minimal risk of lymphoma and non-melanoma skin cancer despite long-term use of thiopurines in patients with inflammatory bowel disease: A longitudinal cohort analysis from northern India.

BACKGROUND AND AIM: Thiopurines are widely used to maintain remission in both ulcerative colitis (UC) and Crohn's disease (CD). Reported effectiveness and tolerability rates have been variable across studies. There are only sparse data in Asian population regarding the long-term efficacy and safety of thiopurines. METHODS: Records of 5351 patients followed up at inflammatory bowel disease (IBD) clinic, All India Institute of Medical Sciences, New Delhi from 2004 to 2020 were evaluated retrospectively. Safety was evaluated in terms of long-term adverse events and development of malignancy. RESULTS: Of 5351 patients with IBD, 1093 who received thiopurine for > 3 months (UC = 788 [proctitis-1.9%, left-sided colitis-44.9%, & pancolitis-53.1%] & CD = 305 [inflammatory-42.6%, stricturing-46.9%, & fistulizing-10.5%]) were included (60.8%-male patients). Follow up and treatment duration on thiopurine were 7 (4-12) years and 39.4 ± 40.3 months, respectively, with 254 (23.2%) patients receiving thiopurines for more than 5 and 68 (6.2%) receiving for more than 10 years. Three hundred and fifty-nine (UC: 249 [31.6%]; CD: 110 [36.1%]; P = 0.1) patients developed adverse events; commonest was myelosuppression (23.4%) followed by gastrointestinal intolerance (3%), flu-like illness (1.7%), and arthralgia/myalgia (1.4%). Myelosuppression was the commonest cause of thiopurine withdrawal. No patient (including 254 patients on thiopurine for ≥ 5 years) developed lymphoma or non-melanoma skin cancer. The cumulative probability of staying free from adverse events in overall IBD cohort at 1, 2, and 5 years was 78.6%, 71.9%, and 68.4%, respectively, and this was comparable between UC and CD (P = 0.09). CONCLUSION: Long-term follow up of patients with IBD from northern India on thiopurine monotherapy demonstrated minimal risk of development of lymphoma as well as non-melanoma skin cancer.

Stringent screening strategy significantly reduces reactivation rates of tuberculosis in patients with inflammatory bowel disease on anti-TNF therapy in tuberculosis endemic region.

BACKGROUND: Anti-tumor necrosis factor (anti-TNF) therapy use in patients with inflammatory bowel disease (IBD) leads to an increased risk of tuberculosis (TB) reactivation despite latent tuberculosis (LTB) screening, especially in TB endemic regions. AIM: We evaluated the effect of stringent screening strategy and LTB prophylaxis on TB reactivation. METHODS: We performed an ambispective comparison between patients who received anti-TNF therapy after January 2019 (late cohort) and between Jan 2005 and Jan 2019 (early cohort). Late cohort patients were subjected to stringent screening criteria which included all: history of past TB/recent contact with active TB, chest X-ray, CT (computed tomography) chest, IGRA (interferon-gamma release assay), TST (tuberculin skin test), and if any positive were given chemoprophylaxis. A cohort comparison was done to evaluate for risk reduction of TB following the stringent screening strategy. RESULTS: One hundred seventy-one patients (63: ulcerative colitis/108: Crohn's disease, mean age diagnosis: 28.5 ± 13.4 years, 60% males, median follow-up duration after anti-TNF: 33 months [interquartile range: 23-57 months]) were included. Among the 112 in the early cohort, 29 (26%) underwent complete TB screening, 22 (19.6%) had LTB, 10 (9%) received chemoprophylaxis, and 19 (17%) developed TB. In comparison, in the late cohort, 100% of patients underwent complete TB screening, 26 (44%) had LTB, 23 (39%) received chemoprophylaxis, and only 1(1.7%) developed TB (p < 0.01). On survival analysis, patients in early cohort had a higher probability of TB reactivation compared with the late cohort (HR: 14.52 (95% CI: 1.90-110.61 [p = 0.01]) after adjusting for gender, age at anti-TNF initiation, concomitant immunosuppression, anti-TNF doses, and therapy escalation. CONCLUSION: The high risk of TB reactivation with anti-TNF therapy in TB endemic regions can be significantly mitigated with stringent LTB screening and chemoprophylaxis.

Aetiology of pyrexia of unknown origin in north India.

The aetiology of pyrexia of unknown origin (PUO) varies dramatically according to epidemiology. We studied the cause and spectrum of PUO in Indian adults. A total of 152 patients (112 prospectively and 40 retrospectively) met Petersdorf and Beeson's criteria. The diagnostic evaluation was guided by potentially diagnostic clues, based on a 'step-wise' approach. The five main categories, i.e. infectious, neoplastic, non-infectious inflammatory, miscellaneous and undiagnosed comprised 43.4%, 21.5%, 19.7%, 2.0% and 12.5%, respectively. The top three causes were tuberculosis (n = 43, 28.3%), lymphoma (n = 19, 12.5%) and adult-onset Still's disease (n = 12, 7.9%). Tuberculosis predominated in all age groups, and about 70% of cases had the extrapulmonary form, the most common being gastrointestinal. Hodgkin and non-Hodgkin lymphomas were equally distributed, but solid malignancies were uncommon. Adult-onset Still's disease was the second commonest cause in adults aged ≤ 40 years. Fever resolved spontaneously in 12/19 cases of undiagnosed cause. Extrapulmonary tuberculosis remains the most prevalent PUO in India.

Spontaneous expulsion of a pulmonary hydatid cyst through bronchial rupture.

The management of a pulmonary echinococcal cyst consists mainly of medical treatment with a scolicidal agent such as albendazole and surgical extirpation. Rarely, a pulmonary cyst may rupture into a bronchus and be spontaneously expelled. This may result in seeding elsewhere in the bronchial tree, or even the alimentary tract, but occasionally, as in our case, may result in a cure.