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Background/Aims@#Gluten-free diet has an excess of fats and simple sugars and puts patients with celiac disease at risk of metabolic complications including metabolic syndrome and fatty liver. We assessed prevalence of metabolic syndrome and fatty liver in two cohorts of celiac disease. @*Methods@#Study was done in 2 groups. In group 1, 54 treatment naïve patients with celiac disease were recruited. Of them, 44 returned after 1-year of gluten-free diet and were reassessed. In group 2, 130 celiac disease patients on gluten-free diet for ≥1 year were recruited. All patients were assessed for anthropometric and metabolic parameters and fatty liver. Metabolic syndrome was defined as per consensus definition for Asian Indians. Fatty liver was defined as controlled attenuation parameter value >263 decibels by FibroScan. @*Results@#In group 1, of 44 treatment naïve patients with celiac disease, metabolic syndrome was present in 5 patients (11.4%) at baseline and 9 (18.2%) after 1 year of gluten-free diet. Patients having fatty liver increased from 6 patients (14.3%) at baseline to 13 (29.5%) after 1year of gluten-free diet (P=0.002). In group 2, of 130 patients with celiac disease on gluten-free diet for a median duration of 4 years, 30 out of 114 (26.3%) and 30 out of 130 patients (23%) had metabolic syndrome and fatty liver, respectively. @*Conclusions@#Patients with celiac disease are at high risk of developing metabolic syndrome and fatty liver, which increases further with gluten-free diet. These patients should be assessed for nutritional and metabolic features and counseled about balanced diet and physical activity regularly.
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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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SARS-CoV-2 pandemic resulted in 92 million cases in a span of one year. The study focuses on understanding population specific variations attributing its high rate of infections in specific geographical regions particularly in USA. Rigorous phylogenomic network analysis of complete SARS-CoV-2 genomes (245) inferred five central clades named a (ancestral), b, c, d and e (subtype e1 & e2). The clade d & e2 were found exclusively comprising of USA. Clades were distinguished by 10 co-mutational combinations in Nsp3, ORF8, Nsp13, S, Nsp12, Nsp2 and Nsp6. Our analysis revealed that only 67.46% of SNP mutations were at amino acid level. T1103P mutation in Nsp3 was predicted to increase protein stability in 238 strains except 6 strains which were marked as ancestral type; whereas co-mutation (P409L & Y446C) in Nsp13 were found in 64 genomes from USA highlighting its 100% co-occurrence. Docking highlighted mutation (D614G) caused reduction in binding of Spike proteins with ACE2, but it also showed better interaction with TMPRSS2 receptor contributing to high transmissibility among USA strains. We also found host proteins, MYO5A, MYO5B, MYO5C had maximum interaction with viral proteins (N, S, M). Thus, blocking the internalization pathway by inhibiting MYO5 proteins which could be an effective target for COVID-19 treatment. The functional annotations of the HPI network were found to be closely associated with hypoxia and thrombotic conditions confirming the vulnerability and severity of infection. We also screened CpG islands in Nsp1 & N conferring ability of SARS-CoV-2 to enter and trigger ZAP activity inside host cell. ImportanceIn the current study we presented a global view of mutational pattern observed in SARS-CoV-2 virus transmission. This provided a who-infect-whom geographical model since the early pandemic. This is hitherto the most comprehensive comparative genomics analysis of full-length genomes for co-mutations at different geographical regions specially in USA strains. Compositional structural biology results suggested that mutations have balance of contrary forces effect on pathogenicity suggesting only few mutations to effective at translation level but not all. Novel HPI analysis and CpG predictions elucidates the proof of concept of hypoxia and thrombotic conditions in several patients. Thus, the current study focuses the understanding of population specific variations attributing high rate of SARS-CoV-2 infections in specific geographical regions which may eventually be vital for the most severely affected countries and regions for sharp development of custom-made vindication strategies.
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The Coronavirus Disease-2019 (COVID-19) that started in Wuhan, China in December 2019 has spread worldwide emerging as a global pandemic. The severe respiratory pneumonia caused by the novel SARS-CoV-2 has so far claimed more than 60,000 lives and has impacted human lives worldwide. However, as the novel SARS-CoV-2 displays high transmission rates, their underlying genomic severity is required to be fully understood. We studied the complete genomes of 95 SARS-CoV-2 strains from different geographical regions worldwide to uncover the pattern of the spread of the virus. We show that there is no direct transmission pattern of the virus among neighboring countries suggesting that the outbreak is a result of travel of infected humans to different countries. We revealed unique single nucleotide polymorphisms (SNPs) in nsp13-16 (ORF1b polyprotein) and S-Protein within 10 viral isolates from the USA. These viral proteins are involved in RNA replication, indicating highly evolved viral strains circulating in the population of USA than other countries. Furthermore, we found an amino acid addition in nsp16 (mRNA cap-1 methyltransferase) of the USA isolate (MT188341) leading to shift in amino acid frame from position 2540 onwards. Through the construction of SARS-CoV-2-human interactome, we further revealed that multiple host proteins (PHB, PPP1CA, TGF-{beta}, SOCS3, STAT3, JAK1/2, SMAD3, BCL2, CAV1 & SPECC1) are manipulated by the viral proteins (nsp2, PL-PRO, N-protein, ORF7a, M-S-ORF3a complex, nsp7-nsp8-nsp9-RdRp complex) for mediating host immune evasion. Thus, the replicative machinery of SARS-CoV-2 is fast evolving to evade host challenges which need to be considered for developing effective treatment strategies.
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Serrated polyps are considered precursor lesions that account for 15% to 30% of colorectal cancers, and they are overrepresented as a cause of interval cancers. They are difficult to detect and resect comprehensively; however, recent data suggest that high definition endoscopy, chromoendoscopy (via spray catheter, pump or orally), narrow band imaging, split-dose bowel preparation and a slower withdrawal (>6 minutes) can all improve detection. Cold snare resection is effective and safe for these lesions, including cold snare piecemeal endoscopic mucosal resection, which is likely to become the standard of care for lesions >10 mm in size. Sessile serrated lesions ≥10 mm in size, those exhbiting dysplasia, or traditional serrated adenomas increase the chance of future advanced neoplasia. Thus, a consensus is emerging: a surveillance examination at 3 years should be recommended if these lesions are detected. Serrated lesions likely carry equivalent risk to adenomas, so future guidelines may consider serrated class lesions and adenomas together for risk stratification. Patients with serrated polyposis syndrome should undergo surveillance every 1 to 2 years once the colon is cleared of larger lesions, and their first degree relatives should undergo screening every 5 years starting at age 40.
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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.
Subject(s)
Humans , Male , Colitis, Ulcerative , Crohn Disease , Follow-Up Studies , Incidence , India , Inflammatory Bowel Diseases , Infliximab , Interferon-gamma Release Tests , Latent Tuberculosis , Mass Screening , Retrospective Studies , Thorax , Tuberculosis , UlcerABSTRACT
BACKGROUND/AIMS: Patients with inflammatory bowel disease (IBD) often require immunosuppressive therapy and blood transfusions and therefore are at a high risk of contracting infections due to hepatitis B (HBV) and hepatitis C (HCV) and human immunodeficiency virus (HIV). In the present study, we assessed the prevalence of these infections in patients with IBD. METHODS: This retrospective study included 908 consecutive patients with IBD (ulcerative colitis [UC], n=581; Crohn's disease [CD], n=327) who were receiving care at a tertiary care center. Ninety-five patients with intestinal tuberculosis (ITB) were recruited as disease controls. Prospectively maintained patient databases were reviewed for the prevalence of HBV surface antigen, anti-HCV antibodies, and HIV (enzyme-linked immunosorbent assay method). HCV RNA was examined in patients who tested positive for anti-HCV antibodies. Prevalence data of the study were compared with that of the general Indian population (HBV, 3.7%; HCV, 1%; HIV, 0.3%). RESULTS: The prevalence of HBV, HCV, and HIV was 2.4%, 1.4%, and 0.1%, respectively, in the 908 patients with IBD. Among the 581 patients with UC, 2.2% (12/541) had HBV, 1.7% (9/517) had HCV, and 0.2% (1/499) had HIV. Among the 327 patients with CD, 2.8% (8/288) had HBV, 0.7% (2/273) had HCV, and 0% (0/277) had HIV. One patient with CD had HBV and HCV coinfection. The prevalence of HBV, HCV, and HIV in patients with ITB was 5.9% (4/67), 1.8% (1/57), and 1.2% (1/84), respectively. CONCLUSIONS: The prevalence of HBV, HCV, and HIV in north Indian patients with IBD is similar to the prevalence of these viruses in the general community. Nonetheless, the high risk of flare after immunosuppressive therapy mandates routine screening of patients with IBD for viral markers.
