关键词： Inflammatory bowel disease   Infliximab   Predictive score   Colectomy   Length of stay  

摘要： Background and Aims Thirty percent of inflammatory bowel disease (IBD) patients hospitalized with flare require salvage therapy or surgery. Additionally, 40% experience length of stay (LOS) > 7 days. No emergency department (ED)-based indices exist to predict these adverse outcomes at admission for IBD flare. We examined whether clinical, laboratory, and endoscopic markers at presentation predicted prolonged LOS, inpatient colectomy, or salvage therapy in IBD patients admitted with flare. Methods Patients with ulcerative colitis (UC) or colonic involvement of Crohn's disease (CD) hospitalized with flare and tested for Clostridioides difficile infection (CDI) between 2010 and 2020 at two urban academic centers were studied. The primary outcome was complex hospitalization, defined as: LOS > 7 days, inpatient colectomy, or inpatient infliximab or cyclosporine. A nested k-fold cross-validation identified predictive factors of complex hospitalization. Results Of 164 IBD admissions, 34% (56) were complex. Predictive factors included: tachycardia in ED triage (odds ratio [OR] 3.35;confidence interval [CI] 1.79-4.91), hypotension in ED triage (3.45;1.79-5.11), hypoalbuminemia at presentation (2.54;1.15-3.93), CDI (2.62;1.02-4.22), and endoscopic colitis (4.75;1.75-5.15). An ED presentation score utilizing tachycardia and hypoalbuminemia predicted complex hospitalization (area under curve 0.744;CI 0.671-0.816). Forty-four of 48 (91.7%) patients with a presentation score of 0 (heart rate < 99 and albumin >= 3.4 g/dL) had noncomplex hospitalization. Conclusions Over 90% of IBD patients hospitalized with flare with an ED presentation score of 0 did not require salvage therapy, inpatient colectomy, or experience prolonged LOS. A simple ED-based score may provide prognosis at a juncture of uncertainty in patient care.

关键词： Inflammatory bowel disease   Oncostatin M   Disease activity   Infliximab   Chemiluminescence immunoassay  

摘要： Background: Although endoscopy is the gold standard to assess disease activity and infliximab efficacy in inflammatory bowel disease (IBD), the invasive, costly, and time-consuming procedure limits its routine applications. We aimed to investigate the clinical value of serum oncostatin M (OSM) as a surrogate biomarker. Methods: Fifty healthy controls, 34 non-IBD patients, and 189 IBD patients who were pre-infliximab treatment (n = 122) or in infliximab maintenance (n = 67) were enrolled. A chemiluminescence immunoassay (CLIA) was constructed to quantify serum OSM concentrations. Receiver operator characteristic (ROC) curve analysis was used to evaluate the performance of blood biomarkers for IBD management. Results: The methodology of CLIA exhibited great analytical performance with a wide linear range of 31.25-25000 pg/mL, a low detection limit of 23.2 pg/mL, acceptable precision, and applicable accuracy. Patients with IBD (121.5 [43.3-249.4] pg/mL, p < 0.001) and non-IBD (72.4 [51.4-129.6] pg/mL, p = 0.005) had higher serum OSM levels than healthy controls (35.8 [23.2-56.4] pg/mL). In the analysis of clinical and endoscopic activity, serum OSM levels were elevated in moderate and severe patients compared to those in remission. IBD patients without mucosal healing had higher serum OSM levels than those with mucosal healing (AUC = 0.843). Besides, serum OSM levels were increased in clinical non-responders (287.3 [127.9-438] pg/mL) compared to responders (24.1 [23.2-53.4] pg/mL, p < 0.001), and showed great recognition ability with an AUC of 0.898. Conclusions: The newly developed methodology of CLIA had great potential for use in the clinic. Elevated serum OSM expression was a promising biomarker of severe disease and infliximab non-response in IBD patients.

关键词： Inflammatory Bowel Disease   Crohn's Disease   Ulcerative Colitis   Biologics  

摘要： Background and Aims Starting biologic treatment early in the course of inflammatory bowel disease (IBD) may be associated with higher efficacy, especially in Crohn’s disease (CD). Methods This was a systematic review and individual-patient data meta-analysis of all placebo-controlled trials of biologics approved for IBD at study inception (October 2015), using Vivli data-sharing platform. The primary outcome was the proportional biologic/placebo treatment effect on induction of remission in patients with short-duration (≤18 months) vs long-duration disease (>18 months) analyzed separately for CD and ulcerative colitis (UC). We used meta-regression to examine the impact of patients’ characteristics on the primary outcome. Results We included 25 trials, testing infliximab, adalimumab, certolizumab, golimumab, natalizumab, or vedolizumab (6168 patients with CD and 3227 patients with UC). In CD, remission induction rates were higher in pooled placebo and patients in active arms with short-duration disease of ≤18 months (41.4% [244 of 589]) compared with disease duration of >18 months (29.8% [852 of 2857], meta-analytically estimated odds ratio, 1.33; 95% confidence interval, 1.09–1.64). The primary outcome, proportional biologic/placebo treatment effect on induction of remission, was not different in short-duration disease of ≤18 months (n = 589, odds ratio, 1.47; 95% confidence interval, 1.01–2.15) compared with longer disease duration (n = 2857, odds ratio, 1.43; 95% confidence interval, 1.19–1.72). In UC trials, both the proportional biologic/placebo remission-induction effect and the pooled biologic-placebo effect were stable, regardless of disease duration. Primary outcome results remained unchanged when tested using alternative temporal cutoffs and when modeled for individual patient’s covariates, including prior anti–tumor necrosis factor exposure. Conclusions There are higher rates of induction of remission with biologics and with placebo in early CD, resulting

关键词： feasibility study   goals of care   inflammatory bowel disease   patient-provider communication   Photovoice   qualitative  

摘要： Background The emotional health of patients with inflammatory bowel disease (IBD) is critical to self-management, but has been difficult to elucidate in routine care. Patients are often unsure how to communicate their preferences and concerns to their providers in ways that could directly inform shared decision making. Photovoice is an established research methodology used to give vulnerable patients a voice through photographic expression, but has not been previously used in gastroenterology or in IBD. Objective To determine the acceptability and feasibility of using Photovoice in an IBD clinic. Patient involvement Patients with IBD took photos in response to open-ended prompts, participated in a focus group, and brainstormed ways to share their experience with clinicians. Methods Enrolled IBD patients received a digital camera, training on basic usage and 10 open-ended prompts related to management of their IBD. Participants completed one-hour in-depth interviews about their photos, which were audio-recorded and professionally transcribed. Three analysts coded transcripts for themes using qualitative analysis software QSR NVivo 11. A subset of patients participated in a focus group about their Photovoice experience. Gastroenterologists were interviewed, using patient photos as prompts, to evaluate feasibility of using Photovoice in the clinic. Results Eleven patients completed the interviews, with five participating in the focus group. Patients shared and discussed a total of 118 photographs. We identified two major themes: disease burden and patient - provider communication. Five IBD physicians reviewed select patient photos and suggested ways to incorporate Photovoice into clinical practice. Discussion Photovoice may be a feasible methodology for patients with IBD and acceptable for providers to use in a clinical setting. Practical value Photovoice may help providers identify patient concerns and make their communication more patient-centred.

关键词： Inflammatory bowel disease   Mucosal integrity testing   Intestinal barrier function   Endoscopy  

摘要： Background While the pathogenesis of inflammatory bowel disease (IBD) is incompletely understood, disruption of epithelial integrity is suspected to play a prominent role in disease initiation and progression. Currently, there is no convenient way to measure this in vivo. Aims Our aim is to determine whether a mucosal integrity (MI) testing device that has been used to measure MI in the esophagus can also be used to measure barrier function in the colon during colonoscopy. Methods Mucosal integrity testing was measured in patients with IBD (n = 17) and controls (n = 7) during colonoscopy. During the procedure, an MI catheter was passed down the working channel of the colonoscope and placed along the mucosal wall to measure MI in the rectum, left, transverse, and right colon. In patients with IBD, MI measurements and biopsies were taken in areas which appeared inflamed when present. We then determined if there was a significant difference in MI between patients with IBD and controls. Results MI was significantly higher in the rectum of patients with IBD (CD and UC combined) versus control colons [767 (618-991) vs. 531 (418-604) ohms, P < 0.01]. There were no significant differences in MI among patients with IBD versus controls in the right, transverse, or left colon. Within the IBD group, there were no significant differences in MI between inflamed versus non-inflamed rectums. There was no correlation between quality of life scores or endoscopic severity with MI, though this study was likely underpowered to detect these differences. Conclusion Rectal MI is significantly higher in patients with IBD versus controls. Future studies are needed to determine how this information can be used clinically.

关键词： Inflammatory bowel disease   Microbiome   Pathogenesis   Immune system   Dysbiosis  

摘要： Inflammatory bowel disease (IBD) is a chronic inflammatory condition of the gastrointestinal system. Previously, it is considered the disease of the western world but now the incidence and prevalence of IBD are increasing globally with urbanization and modernization. Additionally, the major problem is the highest incidence of IBD among children and adolescents. The precise etiology of IBD is unknown and there is no cure for IBD, which is also the reason for increasing the number of cases worldwide. The IBD is a complex interplay of environment, immune system, and microbiota in a genetically susceptible host. Among these factors, the alteration in intestinal microbiota has been detected in IBD patients. The bacterial species associated with IBD include Mycobacterium paratuberculosis, adherent-invasive E. coli (AIEC), Helicobacter pylori, and Campylobacter concisus. Moreover, the efficacy of antibiotics and probiotics further suggests the role of microbes in IBD. However, no study confirmed the bacterial species as a cause of IBD as per Koch's postulates. Thus, still controversies exist regarding the role of microbes in IBD. Therefore, this paper aims to review the current literature to evaluate the role of microbes in IBD that would be a useful inventory of researchers working in this area.

关键词： COVID-19   Vaccine   mRNA-BNT162b2   Serologic Response  

摘要： BACKGROUND & AIM: Patients with inflammatory bowel diseases (IBD), specifically those treated with anti-tumor necrosis factor (TNF)alpha biologics, are at high risk for vaccine-preventable infections. Their ability to mount adequate vaccine responses is unclear. The aim of the study was to assess serologic responses to messenger RNA-Coronavirus Disease 2019 vaccine, and safety profile, in patients with IBD stratified according to therapy, compared with healthy controls (HCs). METHODS: Prospective, controlled, multicenter Israeli study. Subjects enrolled received 2 BNT162b2 (Pfizer/BioNTech) doses. Anti-spike antibody levels and functional activity, anti-TNF alpha levels and adverse events (AEs) were detected longitudinally. RESULTS: Overall, 258 subjects: 185 IBD (67 treated with antiTNF alpha, 118 non-anti-TNF alpha), and 73 HCs. After the first vaccine dose, all HCs were seropositive, whereas similar to 7% of patients with IBD, regardless of treatment, remained seronegative. After the second dose, all subjects were seropositive, however anti-spike levels were significantly lower in anti-TNF alpha treated compared with non-anti-TNF alpha treated patients, and HCs (both P < .001). Neutralizing and inhibitory functions were both lower in anti-TNF alpha treated compared with non-anti-TNF alpha treated patients, and HCs (P < .03;P < .0001, respectively). Anti-TNF alpha drug levels and vaccine responses did not affect anti-spike levels. Infection rate (similar to 2%) and AEs were comparable in all groups. IBD activity was unaffected by BNT162b2. CONCLUSIONS: In this prospective study in patients with IBD stratified according to treatment, all patients mounted serologic response to 2 doses of BNT162b2;however, its magnitude was significantly lower in patients treated with anti-TNF alpha, regardless of administration timing and drug levels. Vaccine was safe. As vaccine serologic response longevity in this group may be limited, vaccine booster dose should be considered.

关键词： antimicrobials   antispasmodic agent   ferrocenyl alkanols   gastrointestinal smooth muscle relaxant   multitarget drug  

摘要： Inflammatory bowel diseases (IBM), such as Crohn's disease, and their common complications represent a global health challenge. Many pyrazole derivatives, such as the spasmolytic drug metamizole, have already found their place among the frequently used therapeutic agents. Alteration of the structure of established therapeutic drugs by introducing a ferrocene moiety was shown to be a promising way for the discovery of new drugs. Herein, two libraries of analogous ferrocenyl (1a-1j) and phenyl alkanols (2a-2j) containing a pyrazole core, among which 17 completely new structures, have been synthesized, and structurally and electrochemically characterized. These compounds, along with the aldehydes used for their synthesis, were tested in parallel for their antispasmodic, acetylcholinesterase-inhibitory, and antimicrobial activities to evaluate their potential as multitarget IBM drugs. The antispasmodic activity was investigated by assessing their effect on both the amplitude and number of spontaneous contractions of isolated rat ileum. Their antimicrobial effect was evaluated against a panel of Gram-positive and Gram-negative bacterial strains and fungi. It was found that several of the evaluated compounds displayed gastrointestinal smooth muscle relaxant activity, among them, 1-(1H-3-ferrocenyl-1-phenylpyrazol-4-yl)-3-methylbutan-1-ol (1d) showed a remarkable effect by superseding the activity of papaverine. Together with the fact that it represents one of the most antimicrobially active investigated compounds, 1d is a good candidate for further pharmacological evaluation as a multitarget drug for IBM.