Digestive Diseases and Sciences最新文献

Background and aims: Metabolic dysfunction-associated steatotic liver disease (MASLD) has a global prevalence of 25%. Studies on incident liver and cardiovascular outcomes in lean (Body mass index: BMI < 25 kg/m², or < 23 kg/m² for Asians) vs. non-lean individuals with MASLD have reported mixed results. We aimed to compare incident clinical outcomes and mortality between lean and non-lean individuals with compensated MASLD cirrhosis in a large national cohort.

Methods: This was a retrospective cohort study of patients with newly diagnosed compensated MASLD cirrhosis in the Veterans Health Administration between 01/2008 and 05/2021. The primary outcome was incident hepatic decompensation, and secondary outcomes were incident major adverse cardiovascular events (MACE) and all-cause mortality. Multivariable Cox proportional hazard models were used to assess association. Fine and Gray competing risk regression was used where applicable.

Results: The study included 15155 patients with MASLD cirrhosis: 1,597 lean and 13558 non-lean patients. Included patients were mostly male (95%), median age was 67 years, and 72.8% were non-Hispanic white. At baseline, the prevalence of diabetes was lower in lean vs. non-lean individuals (46.7 vs. 73.9%, p < 0.001). In multivariable models, lean status was associated with a 64% increased risk of all-cause mortality (aHR = 1.64) but decreased risk of hepatic decompensation (aSHR = 0.67). Lean individuals experienced significantly higher rates of cardiovascular-related mortality (aHR = 1.40).

Conclusion: Lean MASLD patients with compensated cirrhosis had a higher mortality risk but a lower risk of hepatic decompensation than non-lean patients. Despite having a better baseline cardiometabolic profile and similar rates of MACE, lean individuals with MASLD cirrhosis have a higher risk of cardiovascular mortality.

Background: Development of novel colorectal cancer (CRC) screening tests is a dynamic field. Decision analytic modeling based on inputs derived from rigorous prospective studies informs CRC screening guidelines. Exploratory modeling may have a place in early phases of test development.

Methods: We explored whether (1) surrogate endpoints for long-term, programmatic effectiveness, and cost-effectiveness could be potentially informative in early stages of test development and (2) whether rapid exploratory modeling with a web-based tool would be feasible.

Results: First, based on comparisons with published estimates for reductions in CRC mortality with various screening tests in four established decision analytic models of CRC screening, the surrogate endpoint of the number needed to colonoscope to detect one CRC or advanced precancerous lesion (APL) in round 1 of screening appears to hold promise as a measure of clinical effectiveness. Similarly, based on comparisons with published estimates for cost/quality-adjusted life-year gained with screening in the four models, the surrogate endpoint of cost to detect one CRC or APL in round 1 of screening appears to hold promise as a measure of cost-effectiveness. Second, exploration of the impact of lowering the screening initiation age in Israel from age 50 to 45 with the web-based EU-TOPIA tool, compared with the results of a recently published comprehensive modeling study, suggests that exploratory modeling of programmatic screening may be feasible with relatively low time demand vs. that required for typical full-length modeling publications.

Conclusion: Further validation in other models and with a broader set of test performance characteristics is prudent before surrogate endpoints or rapid modeling are incorporated into the novel test development process.

Background: Whether pathophysiological factors differ between males and females with irritable bowel syndrome-diarrhea (IBS-D) remains to be tested. To better understand potential sex differences, males with IBS-D were compared to naturally cycling females and to females with IBS-D taking hormonal contraception on plasma levels of cytokines and gut microbiome characteristics.

Methods: Males and females with Rome III IBS-D completed questionnaires and kept a daily symptom diary for 28 days. Blood and stool samples were collected between days 3 and 8 of the daily diary (estrogen-dominant days in naturally cycling females). Blood samples were analyzed for lipopolysaccharide (LPS)-stimulated and unstimulated cytokine levels. Stool samples were analyzed for microbiota signatures using 16S rRNA sequencing.

Results: Forty-seven participants with IBS-D (13 males, 22 naturally cycling females, 12 females with hormonal contraception use) ages 18 to 50 years were studied. Males had similar unstimulated IL10, IL12P40, IL12P70, IL1β, IL8, and TNFα plasma cytokine levels compared to naturally cycling females, but higher levels compared with females using hormonal contraception. LPS-stimulated IL12P70 levels were lower in both groups of females vs. males. Alpha- and beta-diversity did not differ although differences in genus-level bacteria were found.

Conclusion: Cytokine levels differed between males and females using hormonal contraceptives but not between males and normally cycling females. It is important to consider that naturally cycling females may have a different cytokine and microbiome profile than females using hormonal contraceptives. Whether this portends a sex difference in potential etiologic factors remains to be determined.

Background: Eosinophilic esophagitis (EoE) is an increasingly common cause of food impaction.

Aims: This study aims to provide a nationwide analysis of food impaction in patients with or without EoE diagnosis, concentrating on patient demographics, interventions, outcomes, and development of predictive machine-learning models.

Methods: A retrospective assessment was conducted using Nationwide Emergency Department Sample data from January 1, 2018, to December 31, 2019. We compared patients with food impaction with an associated EoE diagnosis to those without EoE and derived machine-learning models to predict EoE using International Classification of Diseases codes at discharge for identification.

Results: Of 286,886,714 emergency department visits, 146,084 were for food impaction, with 7093 cases coinciding with an EoE diagnosis (4.9%). Patients with EoE were more commonly young men with fewer overall comorbidities but higher incidences of obesity, asthma, gastritis, and allergic rhinitis. A significantly larger proportion in the EoE group (89.6%) underwent esophagogastroduodenoscopy compared to the non-EoE group (51.1%; P < 0.001) and had a higher rate of biopsy during esophagogastroduodenoscopy in the emergency department (54.9% vs 13.4%; P < 0.001). Our machine-learning models, incorporating patient demographics, hospital attributes, and comorbidities, had a sensitivity of 86.1% and an area under the receiver operating characteristic curve of 0.828.

Conclusions: This nationwide study demonstrates that EoE in food impaction is associated with specific patient demographics, comorbidities, and elevated interventions. Our machine-learning models hold promise as screening tools for EoE, aiding medical practitioners in determining the need for biopsy.

Aims: Duodenal Mucosal Resurfacing (DMR) is an endoscopic ablation technique aimed at improving glycemia in patients with type 2 diabetes mellitus (T2DM). Although the exact underlying mechanism is still unclear, it is postulated that the DMR-induced improvements are the result of changes in the duodenal mucosa. For this reason, we assessed macroscopic and microscopic changes in the duodenal mucosa induced by DMR + GLP-1RA.

Methods: We included 16 patients with T2DM using basal insulin that received a combination treatment of a single DMR and GLP-1RA. Endoscopic evaluation was performed before the DMR procedure and 3 month after, and duodenal biopsies were obtained. Histological evaluation was performed and L and K cell density was calculated. In addition, gene-expression analysis and Western blotting was performed.

Results: Endoscopic evaluation at 3 month showed duodenal mucosa with a normal appearance. In line, microscopic histological evaluation showed no signs of villous atrophy or inflammation and unchanged L and K cell density. Unbiased transcriptome profiling and western blotting revealed that PDZK1 expression was higher in responders at baseline and after DMR. GATA6 expression was significantly increased in responders after DMR compared to non-responders.

Conclusion: The absence of macroscopic and microscopic changes after 3 month suggest that improvements in glycemic parameters after DMR do not result from significant histological changes in duodenal mucosa. It is more likely that these improvements result from more subtle changes in enteroendocrine signaling. PDZK1 and GATA6 expression might play a role in DMR; this needs to be confirmed in pre-clinical studies.

Objective: Chronic constipation (CC) more frequently affects the elderly; pelvic floor dysfunction (PFD) may confuse the appraisal of the pathophysiology of CC. The aim was to characterize colonic transit (CT) in elderly with CC with/without PFD.

Design: We conducted retrospective medical records review of 191 patients ≥ 65 years who underwent scintigraphic CT for assessing CC. Overall CT and distribution of isotopes in 4 colonic regions and stool were compared with 179 healthy controls < 65 years and 183 CC < 66 years. Presence of PFD, comorbidities, and concomitant medications were documented. Data shown are median (IQR).

Results: Elderly CC patients were predominantly female (69.3%), aged 70 (67,74) years, with PFD in 56.9%. Elderly CC had overall slower CT (geometric center) at 48 h [2.5 (2.0,3.48)] compared to controls [3.79 (2.69,4.69)], but overall and proximal CT were not different compared to CC < 66 years. Combined ascending and transverse colon (AC + TC) at 48 h was lower in elderly CC [51.1 (14.4,76.5)] % compared to healthy controls [86.5 (53.6, 100)% p < 0.001]. There was no difference in overall CT among elderly CC with and without PFD. Among groups with PFD, the elderly CC (compared to CC < 66y) had higher AC + TC emptying at 24 h (8.6% [IQR 0.0-30.2] vs 0.3% [0.0-20.6] p = 0.042), but not at 48 h.

Conclusion: Overall and proximal CT of elderly with CC was slower to healthy controls, but similar to adults < 66 years with CC. In the 56.9% elderly CC with PFD, overall CT and AC + TC emptying were similar to those without PFD.