American Gastroenterological Association

<bold>Introduction:</bold> Bariatric surgery is a recognized treatment for morbid obesity, affecting weight, cardiovascular function, and oxygen metabolism. Cardiac output (CO) is key for assessing cardiac function during exercise. Inert Gas Rebreathing (IGR) is a non-invasive method for evaluating CO based on the Fick principle (CO = VO2 / AVDiff), providing insight into changes in CO, oxygen consumption (VO2), and arteriovenous oxygen difference (AVDiff). This study assessed the impact of bariatric surgery on these parameters. <bold>Methods:</bold> A prospective study was conducted on 14 patients undergoing sleeve gastrectomy. Hemodynamic parameters at rest and peak exercise were assessed using CPET (Cardiopulmonary Exercise Testing) with IGR before surgery and three months postoperatively. Percentage changes and correlations were analyzed. <bold>Results:</bold> Three months post-surgery, BMI and CO decreased at rest and peak exercise, while AVDiff increased. Peak VO2/kg slightly declined. Body composition analysis showed reduced fat mass and increased muscle mass. ΔAVDiff_rest correlated negatively with Δ%fat mass and positively with Δ%muscle mass. The study is currently ongoing. <bold>Conclusions:</bold> Bariatric surgery improves cardiovascular and metabolic efficiency by reducing CO and increasing AVDiff. Fat loss correlates with higher ΔAVDiff_rest, suggesting enhanced metabolic function, while muscle gain is linked to a greater ΔAVDiff_rest increase. These results suggest that CPET is a valuable tool for assessing the effects of bariatric surgery on cardiovascular and pulmonary function, as well as oxygen metabolism.

Abstract Background The Epi-IBD cohort is a prospective European population-based cohort of 1,508 patients diagnosed in 2010 and 2011 with inflammatory bowel disease (IBD) according to Copenhagen criteria in centres across 17 European countries. The study aims to describe treatment strategies, disease course and prognosis of IBD unclassified (IBDU) across Europe. Methods Patients with IBDU were defined as not fulfilling the Copenhagen diagnostic criteria of Crohn’s disease (CD) or ulcerative colitis (UC), but still required IBD related treatment and monitoring. They were followed prospectively from the time of diagnosis until December 31st, 2020, death, emigration or loss of follow-up. Clinical data on surgery, hospitalizations, and medical treatment were captured throughout the follow-up period and entered into a validated web-database, www.epi-ibd.org. Patients with IBDU were categorised as CD-like, UC-like or mixed CD-UC based on disease location and continuity of the affected bowel segments at diagnosis. Results In total, 129 IBDU patients aged ≥15 years from 22 centres were included. They comprised 8.5% (N=129/1,508) of the total cohort. The disease location was reported in Table 1 where 4 patients had unknown disease location at baseline. At diagnosis, 16% (N=25/129) were CD-like, 52% (N=62/129) were UC-like and 32% (N=42/129) were mixed CD-UC.During the 10-year follow-up, 32% (N=41/129) were re-classified as either CD (N=16) or UC (N=25). The crude 1-, 5-, and 10-year rates for re-classification of diagnosis were 19%, 26% and 32%. The time to initiation of therapies and the distribution of therapies according to re-classification of IBDU diagnosis at baseline are presented in Figure 1 A-B . Advanced therapies were used in 13% (N=17/129) of patients over the 10-year follow-up, and was initiated after a median period of 1.9 years (inter-quartile range 0.9-8.1). An intestinal resection was required in 7% (N=9/129). After 1, 5, and 10 years, 9%, 19% and 26% of the patients diagnosed with IBDU at baseline, respectively, required hospitalisation. Conclusion After 10 years of follow-up, a third of patients initially diagnosed with IBDU were re-classified as either CD or UC. The disease course was in general mild with a low number of patients requiring advanced therapy, intestinal resection, and hospitalization. However, patients who were re-classified as CD or UC were more frequently treated with medical therapies.

Abstract Background Crohn’s disease (CD) progression manifests as bowel damage (BD) and disability; prevention of both is a long-term treatment target in CD. However, the longitudinal characterization of BD and disability in early CD patients remains limited. Methods The Crohn´s Disease Cohort (CROCO) is a multicentre, European cohort study of recently diagnosed CD patients (&amp;lt;12 months following diagnosis) designed to prospectively characterize BD progression and disability. At one year following diagnosis (Y1), BD progression was evaluated using the Lemann Index (LI). Magnetic resonance enterography was completed by all patients, with additional endoscopy and/or pelvic MRI based on disease location. Absence of BD was defined as a LI=0, and any presence of bowel damage was indicated by LI&amp;gt;0. Disability was assessed using the validated IBD-disability index (IBD-DI). We report the LI and its association with prognostic disease features and with IBD-DI at Y1. Results Among 394 included patients, 277 completed Y1 visit; LI could be calculated in 176 [60% male, median age at diagnosis 36.5Y (IQR 25-50)]. Most patients (92%) had ileal or ileocolonic involvement, 68% had inflammatory phenotype, and 11% had perianal disease at diagnosis. At inclusion, 6.2% had undergone surgery (5.1% intestinal and 1.1% perianal). Within the 1st year of disease 66% started advanced therapy, mostly Anti-TNF (59%). By Y1, 68% of the patients exhibited some degree of BD (LI&amp;gt;0), yet the median LI at Y1 was low [0.6 (IQR 0-1.8)]. Univariate analysis revealed an association between the presence of any BD at Y1 and disease location (L2 vs L1 OR: 0.37, 95% CI 0.11-1.22, and L3 vs L1 OR 0.59, 95% CI 0.29-1.18, p= 0.044), disease behaviour (B2/B3 vs B1 OR 8.35, 95% CI 3.11-22.38 p&amp;lt;0.01), and steroids (OR 0.48, 95% CI 0.24-0.97), p= 0.036). In a multivariate logistic model, only disease behaviour at Y1 was significantly associated with any BD (B2/B3 vs B1, aOR 7.61, 95% CI 2.79-20.71)-Table 1. The median IBD-DI in those who completed BD assessment at Y1 was 19.6 [10.4;35.7]; 29% of patients had moderate to severe disability (IBD-DI&amp;gt; 35). No association was observed between LI and IBD-DI at Y1 (OR 0.99, 95%CI 0.97-1.02, p=0.60) and there were no differences in the median LI across disability categories. Fig1 shows the correlation between LI and IBD-DI at Y1. Conclusion In a cohort of newly diagnosed CD patients, approximately one-third exhibited no BD as per the LI evaluation. For those presenting with any degree of BD, the global LI remained low. Complicated disease behaviour was the only factor associated with BD. No association was found with disability assessed by the IBD-DI. Prospective follow-up will determine factors underlying BD variation over time.

ObjectivesIn gastroenterology, sedation demand is increasing, although elderly patients are more prone to experiencing adverse events. Remimazolam, a novel ultra‐short‐acting benzodiazepine, may reduce recovery time after endoscopic procedures.MethodsThis study was a secondary analysis of the investigator‐initiated trial, which investigated the efficacy and safety of remimazolam in gastrointestinal endoscopy (REM‐IICT JP01). Remimazolam sedation was administered during upper gastrointestinal endoscopy. Patients were divided into two groups: 45 non‐elderly and 11 elderly patients (aged ≥65 years). The primary outcome was sedation success. Secondary outcomes included the dose required for sedation, time to awakening, time to regain the ability to walk, and occurrence of adverse events.ResultsEndoscopic sedation was successful in 95.6% of the non‐elderly group and 100% of the elderly group. The total dose of remimazolam was significantly higher in the non‐elderly group (4.0 [3.0–8.0] mg) than in the elderly group (3.0 [2.0–3.0] mg; p < 0.01). The time to awakening was 0.0 (0.0–10.0) min in the non‐elderly group compared to 0.0 (0.0–30.0) min (p = 0.98) in the elderly group. The time to regain the ability to walk was significantly longer in the elderly group (5.0 [0.0–60.0] min) than in the non‐elderly group (5.0 [0.0–30.0] min; p = 0.03). During the procedure, adverse events included hypotension in two cases (4.4%) in the non‐elderly group and hypoxemia in one case (9.0%) in the elderly group.ConclusionsUpper gastrointestinal endoscopy with remimazolam was effective and safe, regardless of age.

Recent studies have combined DNA methyltransferase footprinting of genomic DNA in nuclei with long-read sequencing, resulting in detailed chromatin maps for multi-kilobase stretches of genomic DNA from one cell. Theoretically, nucleosome footprints and nucleosome-depleted regions can be identified using M.EcoGII, which methylates adenines in any sequence context, providing a high-resolution map of accessible regions in each DNA molecule. Here we report PacBio long-read sequence data for budding yeast nuclei treated with M.EcoGII and a bioinformatic pipeline which corrects for three key challenges undermining this promising method. First, detection of m6A in individual DNA molecules by the PacBio software is inefficient, resulting in false footprints predicted by random gaps of seemingly unmethylated adenines. Second, there is a strong bias against m6A base calling as AT content increases. Third, occasional methylation occurs within nucleosomes, breaking up their footprints. After correcting for these issues, our pipeline calculates a correlation coefficient-based score indicating the extent of chromatin heterogeneity within the cell population for every gene. Although the population average is consistent with that derived using other techniques, we observe a wide range of heterogeneity in nucleosome positions at the single-molecule level, probably reflecting cellular chromatin dynamics.