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Anti-tuberculosis (TB) drugs, while being highly potent in vitro, require prolonged treatment to control Mycobacterium tuberculosis ( Mtb ) infections in vivo. We report here that mesenchymal stem cells (MSCs) shelter Mtb to help tolerate anti-TB drugs. MSCs readily take up Mtb and allow unabated mycobacterial growth despite having a functional innate pathway of phagosome maturation. Unlike macrophage-resident ones, MSC-resident Mtb tolerates anti-TB drugs remarkably well, a phenomenon requiring proteins ABCC1, ABCG2 and vacuolar-type H + ATPases. Additionally, the classic pro-inflammatory cytokines IFNγ and TNFα aid mycobacterial growth within MSCs. Mechanistically, evading drugs and inflammatory cytokines by MSC-resident Mtb is dependent on elevated PGE2 signaling, which we verify in vivo analyzing sorted CD45 − Sca1 + CD73 + -MSCs from lungs of infected mice. Moreover, MSCs are observed in and around human tuberculosis granulomas, harboring Mtb bacilli. We therefore propose, targeting the unique immune-privileged niche, provided by MSCs to Mtb , can have a major impact on tuberculosis prevention and cure. Treatment of tuberculosis needs to be taken for several weeks, despite good potency of drugs in vitro. Here, the authors show that mesenchymal stem cells can harbor Mycobacterium tuberculosis providing a niche for evasion of anti-bacterial drugs and cytokines.

Infliximab (IFX) or adalimumab (ADA) use in patients with inflammatory bowel disease (IBD) leads to increased risk of tuberculosis (TB). This meta-analysis evaluated the factors which determine this risk, with special focus on local TB incidence. All studies until January 31, 2019, which reported the development of TB in patients with IBD on IFX/ADA, were included after searching PubMed and Embase. Data regarding disease type, number of patients on IFX/ADA, number of patients who developed TB, mean age at IFX/ADA initiation, median duration of development of TB, and latent TB (LTB) were extracted. The details on local TB incidence were obtained from the World Health Organization database, and the studies were stratified into low (<10/100,000), intermediate (10-40/100,000), and high TB burden countries (>40/100,000). Random effect meta-analysis was performed to calculate the overall pooled prevalence and prevalence based on local TB burden. Of 130,114 patients (128 studies), 373 developed TB (pooled prevalence: 0.08% [95% confidence interval {CI}: 0.05%-0.10%]). The risk increased with increasing TB burden, pooled prevalence being 0.02% (95% CI: 0.02%-0.03%), 0.21% (95% CI: -0.02% to 0.43%), and 1.59% (95% CI: 1.19%-2.00%) for low, intermediate, and high TB burden countries, respectively. Seventy-three percent of patients who developed TB had no evidence of LTB on screening, the proportion being independent of TB burden. There was no effect of disease or treatment type, study type, gender, age at IFX/ADA initiation, and follow-up duration on TB prevalence. TB risk in patients with IBD on IFX/ADA depends on the local TB burden and is independent of disease/treatment type.

The human host gets tremendously influenced by a genetically and phenotypically distinct and heterogeneous constellation of microbial species—the human microbiome—the gut being one of the most densely populated and characterized site for these organisms. Microbiome science has advanced rapidly, technically with respect to the analytical methods and biologically with respect to its mechanistic influence in health and disease states. A clinician conducting a microbiome study should be aware of the nuances related to microbiome research, especially with respect to the technical and biological factors that can influence the interpretation of research outcomes. Hence, this review is an attempt to detail these aspects of the human gut microbiome, with emphasis on its determinants in a healthy state. The present review provides a perspective on the gut microbiome for the clinician interested in conducting related research. The technical factors such as sample collection and storage, type of sample, DNA extraction, sequencing and bioinformatic platform should be uniform for all samples in a given study. Similarly, biological confounders such as diet, age, genetics, geography and environment should be considered in interpreting results of microbiome related study.

BackgroundSarcopenia and visceral fat independently predict poor outcomes in Crohn’s disease (CD). However, combined influence of these parameters on outcomes is unknown, and was investigated in the present study.MethodsThis retrospective study evaluated skeletal muscle index (SMI-cross-sectional area of five skeletal muscles normalized for height), visceral and subcutaneous fat area and their ratio (VF/SC) on single-slice computed tomography (CT) images at L3 vertebrae in CD patients (CT done: January 2012-December 2015, patients followed till December 2019). Sarcopenia was defined as SMI < 36.5 cm2/m2 and 30.2 cm2/m2 for males and females, respectively. Disease severity, behavior, and long-term outcomes (surgery and disease course) were compared with respect to sarcopenia and VF/SC ratio.ResultsForty-four patients [age at onset: 34.4 ± 14.1 years, median disease duration: 48 (24–95) months, follow-up duration: 32 (12–53.5) months, males: 63.6%] were included. Prevalence of sarcopenia was 43%, more in females, but independent of age, disease severity, behavior and location. More patients with sarcopenia underwent surgery (31.6% vs 4%, p = 0.01). VF/SC was significantly higher in patients who underwent surgery (1.76 + 1.31 vs 0.9 + 0.41, p = 0.002), and a cutoff of 0.88 could predict surgery with sensitivity and specificity of 71% and 65% respectively. On survival analysis, probability of remaining free of surgery was lower in patients with sarcopenia (59.6% vs 94.1% p = 0.01) and those with VF/SC > 0.88 (66.1% vs 91.1%, p = 0.1), and still lower in those with both sarcopenia and VF/SC > 0.88 than those with either or none (38% vs 82% vs 100%, p = 0.01).ConclusionsCombination of sarcopenia and high visceral fat predict worse outcomes in CD than either.

Crohn’s disease (CD) is often complicated by strictures and associated with increased risk for surgery. Inflammatory strictures respond to medical therapy, and anti-tumor necrosis factor (TNF) therapy is often used after the failure of steroids. However, data on efficacy of anti-TNF therapy in stricturing CD is limited. We retrospectively analysed the records of patients with stricturing CD who were treated with anti-TNF therapy and were prospectively followed from January 2005 to July 2020. Treatment success was defined as continuation of anti-TNF without the requirement for steroids or parenteral nutrition, switch to other anti-TNF, endoscopic dilation, surgery and severe adverse events leading to the withdrawal of anti-TNF. Fifty-nine patients were included [50-infliximab, 9-adalimumab; mean age-30.1 ± 15 years; males-69.5%; median disease duration-124 (range 30–396) months; median follow-up duration-42 (range 8–180) months]. Ileum was the most common site of stricture (69.5%), 20.3% of patients had colonic strictures, and 64.4% had multiple strictures. 55.9% of patients were steroid dependent and 37.3% were steroid refractory. The median duration of anti-TNF therapy was 14 (range 2–96) months, and 54.2% (n = 32) patients received concomitant immunomodulators. 88% improved with induction (11.8% primary non-response), secondary loss of response was seen in 52.2%, and the cumulative probability of treatment success at 1, 2 and 5 years was 69%, 51%, and 28% respectively. Anaemia at presentation predicted poor response. Only 30% of patients retained biologics on long-term (lack of response, cost, adverse events). 16.9% had adverse events, the commonest being reactivation of tuberculosis (5.1%). Anti-TNF therapy is associated with good short-term treatment success with modest long-term response in stricturing CD.

Most common adverse effect causing cessation of anti‐tubercular treatment (ATT) is drug‐induced liver injury (DILI) which is unpredictable due to its idiosyncratic nature. ATT is the most common cause of DILI and drug‐induced acute liver failure (ALF) in South East Asia. Spectrum of ATT‐DILI ranges from asymptomatic raised transaminases to acute hepatitis to acute liver failure (ALF). ALF due to ATT has a more aggressive course with up to 70% mortality. Both modifiable and non‐modifiable risk factors are involved. Increasing age, female gender, genetic predisposition, poor nutrition, underlying liver disease, and concomitant viral infections make one prone to ATT‐DILI. Thus, pretreatment evaluation is very important. Diagnosis of ATT‐DILI is challenging due to lack of specific diagnostic tests; rather, it is a diagnosis of exclusion. Mild transient asymptomatic raised transaminases is due to hepatic adaptation and does not require any modification or cessation of ATT. Early detection of clinically significant DILI by frequent monitoring is associated with better prognosis and low mortality. Prompt withdrawal of all the potential hepatotoxic drugs is the key step in the management. Since the benefit of first‐line ATT outweighs the monitored risk, reintroduction is always considered after normalization of raised transaminases. Ideal regimen is sequential reintroduction with incremental dosage of least hepatotoxic drug first, but evidence for this is lacking. Since hepatotoxicity rate is similar across different regimens, reintroduction is individualized based on perceived clinical risk. Future research is needed to identify specific biomarker panel for diagnosing ATT‐DILI.

INTRODUCTION:Chronic isolated terminal ileitis (TI) may be seen in Crohn's disease (CD) and intestinal tuberculosis (ITB) in addition to other etiologies that may be managed symptomatically. We developed a revised algorithm to distinguish patients with a specific etiology from a nonspecific etiology.METHODS:Patients with chronic isolated TI followed up from 2007 to 2022 were retrospectively reviewed. A specific (ITB or CD) diagnosis was made based on standardized criteria, and other relevant data were collected. Using this cohort, validation of a previously suggested algorithm was conducted. Furthermore, based on the results of a univariate analysis, a multivariate analysis with bootstrap validation was used to develop a revised algorithm.RESULTS:We included 153 patients (mean age 36.9 ± 14.6 years, males-70%, median duration-1.5 years, range: 0-20 years) with chronic isolated TI of whom 109 (71.2%) received a specific diagnosis (CD-69, ITB-40). On multivariate regression and validation statistics with a combination of clinical, laboratory, radiological, and colonoscopic findings, an optimism corrected c-statistic of 0.975 and 0.958 was obtained with and without histopathological findings, respectively. Revised algorithm, based on these, showed sensitivity, specificity, positive and negative predictive values, and overall accuracy of 98.2% (95% CI: 93.5-99.8), 75.0% (95% CI: 59.7-86.8), 90.7% (95% CI: 85.4-94.2), 94.3% (95% CI: 80.5-98.5) and 91.5%(95% CI:85.9-95.4), respectively. This was more sensitive and specific than the previous algorithm (accuracy 83.9%, sensitivity 95.5%, and specificity 54.6%).DISCUSSION:We developed a revised algorithm and a multimodality approach to stratify patients with chronic isolated TI into specific and nonspecific etiologies with an excellent diagnostic accuracy, which could potentially avoid missed diagnosis and unnecessary side effects of treatment.

Aims/Introduction This study aims to evaluate the prevalence of and factors associated with non‐alcoholic fatty liver disease (NAFLD) in Indian women with prior gestational diabetes mellitus (GDM) diagnosed using International Association of Diabetes and Pregnancy Study Groups (IADPSG) criteria. Materials and Methods This cross‐sectional study (2018–2019) enrolled women with and without prior GDM. Study participants underwent detailed assessments, including relevant medical, obstetric and demographic details; 75‐g oral glucose tolerance test with glucose and insulin estimation at 0, 30 and 120 min; and other relevant biochemical and anthropometric measurements. NAFLD status was defined by ultrasonography. Results We evaluated a total of 309 women (201 and 108 with and without prior GDM, respectively) at a mean age of 31.9 ± 5.0 years and median of 16 months (interquartile range 9–38 months) following the index delivery. The prevalence of NAFLD was significantly higher in women with prior GDM (62.7% vs 50.0%, P = 0.038; grade 2 and 3 disease, 13.9% vs 6.5%). On logistic regression analysis (fully adjusted model), the odds of NAFLD were 2.11‐fold higher in women with prior GDM (95% confidence interval 1.16–3.85, P = 0.014). Overweight/obesity, metabolic syndrome, prediabetes and homeostasis model of assessment of insulin resistance (a measure of insulin resistance) were positively associated with NAFLD, whereas the Matsuda index (a measure of insulin sensitivity) showed a negative association with NAFLD. Conclusions The prevalence of NAFLD is high in women with prior GDM. Such women also have a high burden of cardiometabolic risk factors. Future studies should evaluate the intermediate and long‐term hepatic and cardiovascular risk, and the impact of lifestyle interventions in reducing morbidity in such women. This study evaluated the prevalence and risk factors of non‐alcoholic fatty liver disease in Indian women with prior gestational diabetes mellitus diagnosed using International Association of Diabetes and Pregnancy Study Groups criteria. Ultrasonography of abdomen was used to define non‐alcoholic fatty liver disease status. Prevalence of non‐alcoholic fatty liver disease was significantly higher in women with prior gestational diabetes mellitus (62.7% vs 50.0%, P = 0.038; grade 2 and 3 disease, 13.9% vs 6.5%).

Immune‐mediated inflammatory diseases (IMIDs) are a diverse group of complex inflammatory diseases that result from dysregulated immune pathways and can involve any system of the human body. Inflammatory bowel disease (IBD) is one such disease involving the gastrointestinal (GI) system. With high prevalence in the West and increasing incidence in newly industrialized countries, IBD poses a significant burden on health care. IMIDs of the GI system other than IBD can have similar clinical features, causing diagnostic and therapeutic challenges. Although these disorders share a common pathophysiology, the defects can occur anywhere in the complex network of cytokines, inflammatory mediators, and innate and adaptive systems, leading to unregulated inflammation. Precise knowledge about them will help determine the possible targeted therapy. Thus, it is essential to distinguish these disorders from IBD. This review describes various IMIDs of the GI tract that mimic IBD. Immune‐mediated inflammatory diseases (IMIDs) of the gastrointestinal tract including inflammatory bowel disease (IBD) are a diverse group of complex inflammatory diseases that share similar pathophysiology. IMIDs other than IBD can have similar clinical features causing diagnostic and therapeutic challenges. Thus, it is essential to distinguish these disorders from IBD. This review describes various IMIDs of the gastrointestinal tract that mimic IBD.