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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@#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@#Predictors of short-term outcome of intravenous (IV) steroid therapy in acute severe ulcerative colitis (ASUC) have been well described, but the impact of cytomegalovirus (CMV) infection as a predictor of outcome remains debatable. We investigated the role of quantitative CMV polymerase chain reaction (PCR) as a predictor of short-term outcome in patients with ASUC. @*Methods@#Consecutive patients with ASUC satisfying Truelove and Witts criteria hospitalized at All India Institute of Medical Sciences (AIIMS) from May 2016 to July 2019 were included; all received IV steroid. The primary outcome measure was steroid-failure defined as the need for rescue therapy (with ciclosporin or infliximab) or colectomy during admission. AIIMS’ index (ulcerative colitis index of severity > 6 at day 1+fecal calprotectin > 1,000 μg/g at day 3), with quantitative CMV PCR on biopsy samples obtained at initial sigmoidoscopy were correlated with the primary outcome. @*Results@#Thirty of 76 patients (39%) failed IV corticosteroids and 12 (16%) underwent surgery. Patients with steroid failure had a significantly higher mucosal CMV DNA than responders (3,454 copies/mg [0–2,700,000] vs. 116 copies/mg [0–27,220]; P 2,000 copies/mg (odds ratio [OR], 10.2; 95% confidence interval [CI], 2.6–39.7; P 2,000 copies/mg) independently predicts failure of IV corticosteroids and short-term risk of colectomy and it has an additional value to the established markers of disease severity in patients with ASUC.
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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: The data on the risk of tuberculosis (TB) reactivation with infliximab (IFX) in patients with inflammatory bowel disease (IBD) from TB endemic countries, like India, is limited. The risk of TB reactivation on IFX and its predictors in patients with IBD was assessed. METHODS: This retrospective review included consecutive patients with IBD who received IFX, and were on follow-up from January 2005 to November 2017. The data was recorded on age/disease duration, indications for IFX, screening for latent tuberculosis (LTB) before IFX, response to IFX, incidence and duration when TB developed after IFX, and type of TB (pulmonary [PTB]/extra-pulmonary [EPTB]/disseminated). RESULTS: Of 69 patients (22 ulcerative colitis/47 Crohn’s disease; mean age, 35.6±14.5 years; 50.7% males; median follow-up duration after IFX, 19 months [interquartile range, 5.5–48.7 months]), primary non-response at 8 weeks and secondary loss of response at 26 and 52 weeks were seen in 14.5%, 6% and 15% patients respectively. Prior to IFX, all patients were screened for LTB, 8 (11.6%) developed active TB (disseminated, 62.5%; EPTB, 25%; PTB, 12.5%) after a median of 19 weeks (interquartile range, 14.0–84.5 weeks) of IFX. Of these 8 patients’ none had LTB, even when 7 of 8 were additionally screened with contrast-enhanced chest tomography. Though not statistically significant, more patients with Crohn’s disease than ulcerative colitis (14.9% vs. 4.5%, P=0.21), and those with past history of TB (25% vs. 9.8%, P=0.21), developed TB. Age, gender, disease duration, or extraintestinal manifestations could not predict TB reactivation. CONCLUSIONS: There is an extremely high rate of TB with IFX in Indian patients with IBD. Current screening techniques are ineffective and it is difficult to predict TB after IFX.
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Humanos , Masculino , Colite Ulcerativa , Doença de Crohn , Seguimentos , Incidência , Índia , Doenças Inflamatórias Intestinais , Infliximab , Testes de Liberação de Interferon-gama , Tuberculose Latente , Programas de Rastreamento , Estudos Retrospectivos , Tórax , Tuberculose , ÚlceraRESUMO
BACKGROUND/AIMS: Familial occurrence of inflammatory bowel disease (IBD) is well documented. Reports from Western countries have shown a higher familial occurrence of ulcerative colitis (UC) in first- and second-degree relatives than that in the Asian UC population. No data are currently available from the Indian subcontinent in this regard. We present our data on the familial aggregation of UC. METHODS: Records of patients with UC followed at the Inflammatory Bowel Disease Clinic at the All India Institute of Medical Sciences, New Delhi from August 2004 to January 2016 were reviewed. Details regarding the prevalence of family history and characteristics of these patients were recorded. Affected family members were contacted and disease characteristics were noted for assessment of familial aggregation. RESULTS: Of the 2,058 UC patients included in the analysis, a positive family history of IBD was confirmed in 31 patients (1.5%), 24 (77.4%) of whom had only first-degree relatives affected. All the affected relatives had UC and none had Crohn's disease. Among first-degree relatives, siblings were found to have the highest prevalence of IBD (53.3%), followed by parents (26.7%). CONCLUSIONS: The probability of occurrence of IBD in family members of affected North Indian UC patients is lower than that reported in Western populations.
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Humanos , Povo Asiático , Colite Ulcerativa , Doença de Crohn , Índia , Doenças Inflamatórias Intestinais , Anamnese , Pais , Prevalência , Irmãos , ÚlceraRESUMO
Kartagner's syndrome is a rare autosomal recessive disorder characterized by sinusitis, bronchiectasis and situs inversus. Otitis media is seen in 95% of the individuals with this syndrome due to recurrent respiratory infections and dysfunctional cilia in the middle ear. Earlier research reported the presence of structural and functional deficits in the auditory brainstem following long standing otitis media. However, no such findings have been reported in individuals with this syndrome. Thus, the present case report highlights the results of various audiological tests with special emphasis on investigating the auditory processing abilities in a known case of Kartagner's syndrome. In order to accomplish the aim, the audiological test battery was carried out on a 42 year old male patient diagnosed as having Kartagner's syndrome. The basic audiological tests, including immittance audiometry, pure tone audiometry, otoacoustic emission and auditory brainstem response (using click stimulus) results indicated the presence of mild to moderate mixed hearing loss in both ears. However, results of the auditory brainstem response (using speech stimulus) pointed toward abnormal speech processing skills. Thus, the behavioral test battery approach (including speech perception in noise test, gap detection test, temporal modulation transfer function test and duration pattern test) was followed and the findings suggested presence of auditory closure and temporal processing deficit. The outcome of the case study recommends that a complete test battery approach involving psychoacoustic tests should be used to assess such cases and auditory rehabilitation should be suggested accordingly.
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UNLABELLED: In the recent past, there has been a resurgence of interest in Chikungunya virus (CHIKV) attributed to massive outbreaks of Chikungunya fever in the South-East Asia Region. This has reflected in substantial increase in submission of CHIKV genome sequences to NCBI (National Center for Biotechnology Information) database. Hereby we submit a database "CHIKVPRO" containing structural and functional annotation of Chikungunya virus proteins (25 strains) submitted in the NCBI repository. The CHIKV genome encodes for 9 proteins:4 non-structural and 5 structural. The CHIKVPRO database aims to provide the virology community with a single accession authoritative resource for CHIKV proteome- with reference to physiochemical and molecular properties, proteolytic cleavage sites, hydrophobicity, transmembrane prediction, and classification into functional families using SVMProt and other Expasy tools. AVAILABILITY: The database is freely available at http://www.chikvpro.info/