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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.
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Background/Aims@#Intestinal tuberculosis (ITB) and Crohn’s disease (CD) frequently present with a diagnostic dilemma because of similar presentation. Interferon-gamma release assay (IGRA) has been used in differentiating ITB from CD, but with sparse reports on its diagnostic accuracy in tuberculosis endemic regions and this study evaluated the same. @*Methods@#Patients with definitive diagnosis of ITB (n=59) or CD (n=49) who underwent IGRA testing (n=307) were retrospectively included at All India Institute of Medical Sciences, New Delhi (July 2014 to September 2021). CD or ITB was diagnosed as per standard criteria. IGRA was considered positive at >0.35 IU/mL.Relevant data was collected and IGRA results were compared between ITB and CD to determine its accuracy. @*Results@#Among 59 ITB patients (mean age, 32.6±13.1 years; median disease duration, 1 year; male, 59.3%), 24 were positive and 35 tested negative for IGRA. Among 49 CD patients (mean age, 37.8±14.0; median disease duration, 4 years; male, 61.2%), 12 were positive and 37 tested negative for IGRA. Hence, for diagnosing ITB, IGRA showed a sensitivity, specificity, positive and negative predictive values of 40.68%, 75.51%, 66.67%, and 51.39%, respectively. The area under the curve of IGRA for ITB diagnosis was 0.66 (95% confidence interval, 0.55–0.75). In a subset (n=64), tuberculin skin test (TST) showed sensitivity, specificity, positive and negative predictive values of 64.7%, 73.3%, 73.3%, and 64.71%, respectively. IGRA and TST were concordant in 38 (59.4%) patients with κ=0.17. @*Conclusions@#In a tuberculosis endemic region, IGRA had poor diagnostic accuracy for differentiating ITB from CD, suggesting a limited value of IGRA in this setting.
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Background/Aims@#Intestinal tuberculosis (ITB) is difficult to diagnose due to poor sensitivity of definitive diagnostic tests. ITB may be associated with concomitant pulmonary tuberculosis (PTB) which may remain undetected on chest X-ray. We assessed the role of contrast enhanced computed tomography (CECT) chest in detecting the prevalence of active PTB, and increasing the diagnostic yield in patients with suspected ITB. @*Methods@#Consecutive treatment naïve patients with suspected ITB (n=200) who underwent CECT chest (n=88) and had follow-up duration>1 year were recruited in this retrospective study (February 2016 to October 2018). ITB was diagnosed in the presence of caseating granuloma, positive acid fast stain or culture for Mycobacterium tuberculosis on biopsy, presence of necrotic lymph nodes (LNs) on CT enterography or positive response to anti-tubercular therapy. Evidence of active tuberculosis on CECT-chest was defined as presence of centrilobular nodules with or without consolidation/miliary nodules/thick-walled cavity/enlarged necrotic mediastinal LNs. @*Results@#Sixty-five of eighty-eight patients (mean age, 33.8±12.8 years; 47.7% of females) were finally diagnosed as ITB (4-caseating granuloma on biopsy, 12-necrotic LNs on CT enterography, 1-both, and 48-response to anti-tubercular therapy) and 23 were diagnosed as Crohn’s disease. Findings of active TB on CECT chest with or without necrotic abdominal LNs were demonstrated in 5 and 20 patients, respectively. No patient with Crohn’s disease had necrotic abdominal LNs or active PTB. Addition of CECT chest in the diagnostic algorithm improved the sensitivity of ITB diagnosis from 26.2% to 56.9%. @*Conclusions@#Addition of CECT chest significantly improves the sensitivity for definite diagnosis in a patient with suspected ITB.
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Background/Aims@#Existing therapeutic options for complicated Crohn’s disease (CD) like biologics and surgery are limited by inadequate long-term efficacy, cost, and adverse effects. Tissue hypoxia is important in CD pathogenesis and may be ameliorated with hyperbaric oxygen therapy (HBOT). We assessed the efficacy and tolerability of HBOT in small bowel stricturing CD. @*Methods@#This pilot study included patients of small bowel stricturing CD (from April 2019 to January 2020) who underwent HBOT. These patients were refractory to conventional medical treatment or had multiple strictures not amenable to resection. Each session of HBOT was given for 60 minutes with a pressure of 1.5–2.5 atm. Clinical, biochemical responses and Short Inflammatory Bowel Disease (SIBD) questionnaire were evaluated at 2 and 6 months, and radiological response was evaluated at 6 months. @*Results@#Fourteen patients (mean age, 42.9±15.7 years; male, 50%) were subjected to 168 HBOT sessions. Thirteen patients (92.7%) had strictures and 1 patient had enterocutaneous fistula in addition. Median number of HBOT sessions was 11 (range, 3–20) which were administered over a median of 4 weeks. Most patients tolerated it well except 1 who had hemotympanum. At 2 and 6 months of follow-up, 64.2% of patients had a clinical response, 50% and 64.2% of patients had clinical remission respectively. Steroid-free clinical remission was seen in 8 (57%) of patients with radiological improvement in 50%. There was a significant improvement in SIBD scores at 2-month follow-up (59.4 vs. 44.5, P=0.03). @*Conclusions@#HBOT can be a safe and effective therapeutic option in patients with stricturing small bowel CD refractory to conventional medical treatment.
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Background/Aims@#Exclusive enteral nutrition (EEN), an established modality for pediatric Crohn’s disease (CD) is seldomly utilized in adults. The present study reports the outcome of EEN in adult CD patients at a tertiary care hospital in India. @*Methods@#This was a retrospective analysis of CD patients who received EEN as a sole modality/adjunct to other treatment. The primary and secondary outcomes changed in Crohn’s Disease Activity Index (CDAI), and clinical response (decline in CDAI > 70), respectively, at 4 and 8 weeks. Subgroup analysis evaluated response across different phenotypes, EEN formulations and prior treatment. Linear mixed effect model was created to assess the predictors of EEN response. @*Results@#Thirty-one CD patients received EEN over median duration of 4 weeks (range, 2–6 weeks). CDAI showed a significant improvement post EEN at 4 (baseline 290 [260–320] vs. 240 [180–280], P= 0.001) and 8 weeks (baseline 290 [260–320] vs. 186 [160–240], P= 0.001), respectively. The cumulative clinical response rates at 4 and 8 weeks were 37.3% and 80.4% respectively. The clinical response rates at 8 weeks across B1 (n = 4), B2 (n = 18) and B3 (n = 9) phenotypes were 50%, 78.8% and 100% respectively (log-rank test, P= 0.093). The response rates at 8 weeks with polymeric (n = 8) and semi-elemental diet (n = 23) were 75% and 82.6%% respectively (log-rank test, P= 0.49). Baseline CDAI (odds ratio, 1.008; 95% confidence interval, 1.002–1.017; P= 0.046) predicted response to EEN. @*Conclusions@#EEN was effective in inducing clinical response across different phenotypes of CD. Baseline disease activity remained the most important predictor of clinical response to EEN.
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Background/Aims@#Exclusive enteral nutrition (EEN), an established modality for pediatric Crohn’s disease (CD) is seldomly utilized in adults. The present study reports the outcome of EEN in adult CD patients at a tertiary care hospital in India. @*Methods@#This was a retrospective analysis of CD patients who received EEN as a sole modality/adjunct to other treatment. The primary and secondary outcomes changed in Crohn’s Disease Activity Index (CDAI), and clinical response (decline in CDAI > 70), respectively, at 4 and 8 weeks. Subgroup analysis evaluated response across different phenotypes, EEN formulations and prior treatment. Linear mixed effect model was created to assess the predictors of EEN response. @*Results@#Thirty-one CD patients received EEN over median duration of 4 weeks (range, 2–6 weeks). CDAI showed a significant improvement post EEN at 4 (baseline 290 [260–320] vs. 240 [180–280], P= 0.001) and 8 weeks (baseline 290 [260–320] vs. 186 [160–240], P= 0.001), respectively. The cumulative clinical response rates at 4 and 8 weeks were 37.3% and 80.4% respectively. The clinical response rates at 8 weeks across B1 (n = 4), B2 (n = 18) and B3 (n = 9) phenotypes were 50%, 78.8% and 100% respectively (log-rank test, P= 0.093). The response rates at 8 weeks with polymeric (n = 8) and semi-elemental diet (n = 23) were 75% and 82.6%% respectively (log-rank test, P= 0.49). Baseline CDAI (odds ratio, 1.008; 95% confidence interval, 1.002–1.017; P= 0.046) predicted response to EEN. @*Conclusions@#EEN was effective in inducing clinical response across different phenotypes of CD. Baseline disease activity remained the most important predictor of clinical response to EEN.