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Background and Aims. Sarcopenia is a prognostic factor of outcomes for various diseases, but reports on sarcopenia in patients with Crohn's disease (CD) are few. We aim to determine the prevalence of sarcopenia and assess the role of sarcopenia in postoperative complications in patients with CD at a tertiary referral center. Methods. Patients who underwent intestinal surgery for CD from January 2013 to October 2019 were retrospectively enrolled. The L3 skeletal muscle mass index (SMI) was used to identify sarcopenia. Demographic data, preoperative laboratory data, surgical details, and hospital outcomes were recorded. The factors associated with postoperative complications were evaluated through univariate and multivariate analyses. Results. One hundred and twenty-four patients were enrolled. Thirty-four of them (27.4%), including 11 males, were diagnosed with sarcopenia. Compared with patients without sarcopenia, sarcopenic patients had a significantly lower BMI (P < 0.001); lower preoperative serum albumin (P = 0.006), prealbumin (P = 0.030), and hemoglobin levels (P < 0.001); longer hospital stay (34.4 ± 26.8 days vs. 22.8 ± 15.6 days, P = 0.003); and more occurrences of complications (41.2% vs. 23.3%, P = 0.049). The overall incidence of postoperative complications was 28.2%. Infection (51.4%) and intestinal fistula (22.9%) were the most common among such complications. Through the multivariate analysis, sarcopenia was identified as an independent risk factor for major postoperative complications (odds ratio = 3.974 , 95 % CI = 1.171 –13.489, P = 0.027). Conclusion. Sarcopenia is common in patients with CD requiring bowel resection, and it significantly increases the risk of major postoperative complications. [ABSTRACT FROM AUTHOR]

Leveraging stromal cells: Reducing the activation of proinflammatory signaling pathways has been shown to have therapeutic effects in animal models and in patients with inflammatory bowel disease (IBD). However, a substantial proportion of patients do not respond to available therapies. Here, Gao et al. investigated the endogenous immune mechanisms activated in IBD to identify potential therapeutic targets. The authors identified a population of stromal cells marked by Twist2 that suppresses inflammation in animal models of IBD by producing and suppressing inflammatory M1 macrophage polarization. In patients, they identified an inverse correlation between severity of disease and stromal cell Cox2 expression. Targeting this endogenous signaling might be an effective strategy to reduce inflammation in IBD. Inflammatory bowel disease (IBD) affects 0.3% of the global population, yet the etiology remains poorly understood. Anti-inflammation therapy has shown great success, but only 60% of patients with IBD benefit from it, indicating that new targets are needed. Here, we report the discovery of an intrinsic counter regulatory mechanism in colitis pathogenesis that may be targeted for IBD treatment. In response to microbial invasion, resident Vimentin+ stromal cells, connective tissue cells genetically marked by Twist2, are activated during the propagation phase of the disease, but not during initiation and resolution phases, and become a primary source of prostaglandin E2 (PGE2). PGE2 induction requires a nuclear factor κB–independent, TLR4-p38MAPK-Cox2 pathway activation. Ablation of each of the pathway genes, but not Rela or Tgfb1, in Twist2 cells enhanced M1 macrophage polarization and granulocyte/T helper 1 (TH1)/TH17 infiltration and aggravated colitis development. PGE2 administration ameliorated colitis in mouse models with defective PGE2 production but not in animals with normal PGE2 induction. Analysis of clinical samples and public domain data revealed increased expression of Cox2, the rate-limiting enzyme of PGE2 biosynthesis, in inflamed tissues, and especially in colon Vimentin+Twist2+ stromal cells, in about 60% of patients with active Crohn's disease or ulcerative colitis. Moreover, Cox2 protein expression was negatively correlated with disease severity, suggesting an involvement of stromal cells in IBD pathogenesis. Thus, the study uncovers an active immune pathway in colitic inflammation that may be targeted to treat patients with IBD with defects in PGE2 production. [ABSTRACT FROM AUTHOR]

Crohn's disease is a chronic disorder that typically affects the gastrointestinal tract. The increased incidence in the recent years, especially in Asian countries, prompts for performing studies and gain newer insights into the etiology and pathogenesis of the disease. Among other causative factors, gut microbiome and its cross-talk with the salivary microbiome is a known factor that has a plausible role in the pathogenesis of Crohn's disease. The gut microbiome has been extensively studied, however, the salivary microbiome and its dynamics during different phases of this disease remain understudied. In this study, we obtained saliva samples from the patients during active and remission phases of the disease and compared them with control samples and highlighted the differences in taxonomic as well as predicted functional pathways among them. Our results indicated that the α and β diversities were significantly lower during the active phase in contrast with remission phase and healthy samples. In general, Firmicutes were most abundant among the three sample groups, followed by Bacteroidetes and Proteobacteria. Genus level distribution highlighted Streptococcus, Neisseria, Prevotella, Haemophilus , and Veillonella as the five most abundant taxa. Differential abundance analysis of the three sample groups identified significant enrichment of 30 bacterial taxa in the active phase that included g_ Prevotella , f_ Prevotellaceae , and p_ Bacteroidetes. Furthermore, remission phase and control also exhibited significant enrichment of 24 and 22 bacterial taxa, respectively. Eleven differentially abundant pathways were also identified, four were significantly enriched in healthy controls whereas other seven were significantly enriched in active phase of the disease. Several important pathways, such as ribosome biogenesis and Energy metabolism were depleted in the active phase. Our study has highlighted several taxa and functional categories that could be implicated with the onset of Crohn's disease and thus have the potential to serve as biomarkers of the active disease. However, these findings require further validation through functional studies in the future. [ABSTRACT FROM AUTHOR]

Background. Double-balloon enteroscopy (DBE) is widely used worldwide. However, comparisons between the diagnostic yields in adults and the elderly remain scarce. Aim. The aim of this study is to compare the diagnostic yields and safety of DBE between adults and elderly with obscure gastrointestinal bleeding and incomplete small bowel obstruction. Method. We retrospectively reviewed patients who underwent DBE with indication of obscure gastrointestinal bleeding or incomplete small bowel obstruction in Ruijin Hospital and classified them into adults (18–64 years old) and elderly (≥65 years old). Clinical characteristics, diagnostic yields, and postoperative complications were collected and further analyzed. Results. A total of 877 DBE procedures, 729 in adults and 148 in the elderly, were performed. In the patients with OGIB, the adults showed a higher frequency of Meckel's diverticulum compared with the elderly (4.6% vs. 0.9%, P = 0.032). Angioectasia was higher in frequency in the elderly than in the adults (25.9% vs. 17.9%, P = 0.048). In patients with incomplete small bowel obstruction, the elderly were more likely to have adenocarcinoma than the adults (19.4% vs. 7.1%, P = 0.038). The adults had higher tendency to have Crohn's disease than the elderly (23.4% vs. 8.3%, P = 0.045). Most of the postoperative complications were mild. The adults and elderly displayed comparable tolerance to DBE (P > 0.05) Conclusion. DBE has a high diagnostic yield in small bowel disorders, and a slight difference in disease spectrum was observed between the adults and elderly. DBE can be well-tolerated in the elderly. [ABSTRACT FROM AUTHOR]

Aim. To determine the risk factors of nonadherence to azathioprine (AZA) maintenance therapy for Crohn's disease (CD) and to evaluate the influence of patients' educational program on adherence to AZA maintenance therapy. Methods. Patients receiving AZA as maintenance therapy for CD were enrolled. Demographic data, clinical data, and usage information were collected. Univariate and multivariate analyses were performed to identify the risk factors of nonadherence. Then, patients' educational program was conducted. One year after the program, the improvements in adherence and relapse rates were compared between educational and noneducational groups. Results. A total of 378 CD patients receiving AZA as maintenance therapy were enrolled from September 2008 to September 2018. Nonadherence occurred in 43.9% (166/378) of patients. Univariate analysis revealed that young age, education, alcoholism, anxiety, depression, concern belief, and lack of necessity belief and AZA knowledge were risk factors of nonadherence (P < 0.05). Multivariate logistic regression showed that anxiety (OR 6.244, 95% CI 2.563–15.213), depression (OR 3.801, 95% CI 1.281–11.278), and concern belief (OR 19.531, 95% CI 3.393–120.732) were independent risk factors of nonadherence. Necessity belief (OR 0.961, 95% CI 0.925–0.999) and AZA knowledge (OR 0.823, 95% CI 0.758–0.903) were protective factors of adherence. One year after the AZA educational program, the necessity belief, AZA knowledge, and adherence of the educational group significantly improved (P < 0.05). Concern belief was significantly lower in the educational group than that in the noneducational group (P < 0.05). Moreover, the noneducational group suffered significantly higher endoscopic relapse rates than that the educational group (15.9% vs. 30.1%, P = 0.035). Conclusions. Nonadherence occurred frequently in CD patients receiving AZA maintenance therapy. Educational programs could improve patients' adherence mainly by promoting their beliefs and knowledge of AZA and could reduce relapse rates during treatment. [ABSTRACT FROM AUTHOR]

Background: Patients with newly diagnosed Crohn��s disease (CD) are associated with impaired physical and psychological well-being. These psychological characteristics are dynamic with the course of disease and could be influenced by medical treatment. Infliximab is effective and widely used in moderate-to-severe CD patients. The aim of this study was to evaluate the improvement of psychological status after infliximab treatment in patients with newly diagnosed CD.Methods: Newly diagnosed moderate-to-severe CD patients were prospectively enrolled in our study. Infliximab 5 mg/kg was administered at weeks 0, 2, 6, 14, 22, and 30. Outcomes including disease severity, illness perceptions, coping strategies, anxiety, depression, and quality of life (QoL) were measured at baseline, week 14, and week 30.Results: Eighty-two patients completed our study. The rates of clinical remission at weeks 14 and 30 were 59/82 (72.0%) and 58/82 (70.7%), respectively. Patients who achieved clinical remission at weeks 14 and 30 significantly improved in illness perceptions (P [ABSTRACT FROM AUTHOR]

Objective. To evaluate the efficacy of infliximab (IFX) monotherapy versus infliximab-azathioprine sequential treatment in Crohn’s disease (CD) patients. Methods. Patients newly diagnosed with CD using IFX as induction therapy were enrolled. After 6 times of IFX infusions, they were divided into IFX monotherapy group and IFX-AZA sequential therapy group. Clinical remission rates were assessed at weeks 57, 84, 111, and 138 while endoscopic remission rates were assessed at weeks 84 and 138 to evaluate the efficacy of these two groups. Results. A total of seventy-nine patients had accomplished 138-week follow-up. At weeks 84 and 138, the deep remission rate (18/22 and 17/22) of IFX monotherapy group was significantly higher compared to IFX-AZA sequential therapy group (26/57 and 21/57) (P=0.004 and 0.001, resp.). Similar findings were found in complete endoscopic remission rate. The clinical remission rates of IFX monotherapy group were similar to that of IFX-AZA sequential therapy group (P>0.05). At weeks 84 and 138, the endoscopic remission rate and the endoscopic improvement rate between these two groups displayed no significant difference (P>0.05). Conclusion. IFX monotherapy provides higher deep remission rate compared with IFX-AZA sequential therapy in two-year maintenance therapy. For patients who could not receive prolonged IFX therapy, IFX-AZA sequential therapy is acceptable, though long-term efficacy remains to be seen. [ABSTRACT FROM AUTHOR]

Th1 and Th17 cells, and their associated cytokines, have been associated with the pathogenesis of Crohn’s disease. Berberine (BBR), a compound long used in traditional Chinese medicines, has been reported to have therapeutic effects in treating experimental colitis. In this study, we show that BBR had a protective effect on mice with TNBS-induced colitis. BBR inhibited levels of IFN-γ, IL-17, IL-6, IL-1β and TNF-α both in the local colon and sera, and transiently increased levels of IL-22. BBR also markedly increased sIgA expression in the colon. BBR had pronounced effects on macrophage populations. Treatment with BBR adjusted the M2/M1 ratio. In addition, BBR exerted effects on adaptive immunity by suppressing numbers of Th1 and Th17 cells, as well as expression levels of their associated cytokines and transcriptional factors. BBR downregulated STAT3 and STAT1 phosphorylation, and inhibited phosphorylation of NF-kB. In vitro experiments showed that BBR inhibited the differentiation of Th17 and, to a lesser degree, Th1 cells, without affecting regulatory T cells. Therefore, we conclude that BBR plays a regulatory role in modulating the balance of immune responses in TNBS-induced colitis. Our study will help us understand the regulatory mechanisms exerted by BBR in the treatment of IBD. [ABSTRACT FROM AUTHOR]