ULTRA-PROCESSED FOOD CONSUMPTION AND RISK OF GALLSTONE DISEASE: ANALYSIS OF THREE PROSPECTIVE COHORTS.

BACKGROUND: Majority of dietary intake in US adults comes from ultra-processed foods (UPFs), which have been linked to several adverse health outcomes. Gallstone disease is highly prevalent and constitutes a significant burden to the US health system but remains understudied. OBJECTIVE: This study aims to investigate the association between UPF consumption and incident gallstone disease risk. DESIGN: In this analysis, 44,149 males in the Health Professionals' Follow-up Study (HPFS: 1986-2022), 71,145 females in the Nurses' Health Study (NHS: 1986-2021) & 90,932 females in the Nurses' Health Study II (NHS II: 1991-2021) were prospectively followed. Dietary intake was quadrennially assessed with semi-quantitative food frequency questionnaires and used to identify UPFs. The primary outcome was defined as cholecystectomy. Cox proportional hazards model was used to estimate adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs). RESULTS: Baseline median age was 54y in HPFS, 53y in NHS and 36y in NHS II. We identified 32,374 incident gallstone disease cases over 5,077,059 person-years. Participants in the highest UPF quintile had a higher incidence of gallstone disease compared to those in the lowest quintile (aHR: 1.29, 95% CI: 1.24-1.36, p<0.001). The incremental risk of incident gallstone disease was 2.8% per daily serving (95% CI: 2.4%-3.2%, p<0.001). This risk was driven by sugar-sweetened beverages and artificially-sweetened beverages on UPF subgroup-analyses. The proportion of risk mediated by obesity was 12.8% (95% CI: 7.7%-20.5%, p <0.001) in HPFS, 14.3% (95% CI: 10.4%-19.4%, p<0.001) in NHS and 39.4% (95% CI: 31.2%-48.1%, p<0.001) in NHS II. The partial population attributable risk was estimated at 15.9% (95% CI: 13.4%-18.3%). CONCLUSION: UPF consumption is associated with a higher risk of gallstone disease, particularly consumption of sugar-sweetened beverages and artificially-sweetened beverages. A substantial proportion of this risk is potentially mediated by obesity in younger females.

A natural language processing algorithm accurately classifies steatotic liver disease pathology to estimate the risk of cirrhosis.

BACKGROUND: Histopathology remains the gold standard for diagnosing and staging metabolic dysfunction-associated steatotic liver disease (MASLD). The feasibility of studying MASLD progression in electronic medical records based on histological features is limited by the free-text nature of pathology reports. Here we introduce a natural language processing (NLP) algorithm to automatically score MASLD histology features. METHODS: From the Mass General Brigham health care system electronic medical record, we identified all patients (1987-2021) with steatosis on index liver biopsy after excluding excess alcohol use and other etiologies of liver disease. An NLP algorithm was constructed in Python to detect steatosis, lobular inflammation, ballooning, and fibrosis stage from pathology free-text and manually validated in >1200 pathology reports. Patients were followed from the index biopsy to incident decompensated liver disease accounting for covariates. RESULTS: The NLP algorithm demonstrated positive and negative predictive values from 93.5% to 100% for all histologic concepts. Among 3134 patients with biopsy-confirmed MASLD followed for 20,604 person-years, rates of the composite endpoint increased monotonically with worsening index fibrosis stage (p for linear trend <0.005). Compared to simple steatosis (incidence rate, 15.06/1000 person-years), the multivariable-adjusted HRs for cirrhosis were 1.04 (0.72-1.5) for metabolic dysfunction-associated steatohepatitis (MASH)/F0, 1.19 (0.92-1.54) for MASH/F1, 1.89 (1.41-2.52) for MASH/F2, and 4.21 (3.26-5.43) for MASH/F3. CONCLUSIONS: The NLP algorithm accurately scores histological features of MASLD from pathology free-text. This algorithm enabled the construction of a large and high-quality MASLD cohort across a multihospital health care system and disclosed an accelerating risk for cirrhosis based on the index MASLD fibrosis stage.

Effect of combined tobacco use and type 2 diabetes mellitus on prevalent fibrosis in patients with MASLD.

BACKGROUND: Several studies have investigated the independent effect of cigarette smoking or type 2 diabetes mellitus (T2DM) on MASLD. However, the interaction effect between tobacco consumption and T2DM on MASLD severity remains underexplored. In this study, we assessed the combined effect of tobacco use and T2DM on hepatic fibrosis in MASLD. METHODS: We conducted a single-center retrospective cross-sectional analysis of eligible participants from the Mass General Brigham Fibroscan© database. The participants were divided into 3 groups: those with T2DM and a history of tobacco use (primary exposure group), those with T2DM but no history of tobacco use (secondary exposure group), and those without T2DM and no history of tobacco use (reference group). An additional model was developed, which included a fourth group, participants with a history of tobacco use but no T2DM. The likelihood of fibrosis was determined using a defined fibrosis-4 index cutoff value of 1.3. In addition, we computed the estimated marginal means for liver stiffness measurement and compared the values among the exposure groups. Bivariable and multivariable logistic regression models were used to explore the associations between the exposure groups and the risk for hepatic fibrosis. RESULTS: Overall, 598 individuals were enrolled in the study. The bivariable logistic regression model revealed a significant independent association between T2DM, combined smoking and T2DM, and the outcome of interest, fibrosis. Age, sex, metabolic syndrome, aspirin use, statin use, hemoglobin A1C (A1C), and total bilirubin level were also significantly associated with fibrosis. In the adjusted fibrosis-4 multivariable model (comparing exposure groups to controls), cigarette smoking and T2DM interaction had higher odds of prevalent fibrosis (aOR, 3.04; 95% CI, 1.62-5.76), compared to those with T2DM alone (aOR 2.28; 95% CI, 1.37-3.85). The continuous liver stiffness measurement comparison across the exposure group showed an estimated marginal means of 6.26 (95% CL: 5.58-6.94), 7.54 (95% CL: 6.78-8.30), and 7.88 (6.78-8.99) for the reference group, T2DM only group, and tobacco-T2DM group, respectively. The diabetes-only group and the combined tobacco-T2DM group had statistically significant associations with liver stiffness measurement (p values: 0.013 and 0.014, respectively). CONCLUSION: Although diabetes is independently associated with hepatic fibrosis in patients with MASLD, the combination of tobacco consumption and diabetes is associated with a higher prevalence of fibrosis. Therefore, lifestyle change through tobacco use cessation in patients with diabetes could be beneficial in reducing the incidence of liver fibrosis among individuals with MASLD.

Artificial intelligence in gastroenterology and hepatology: how to advance clinical practice while ensuring health equity.

Artificial intelligence (AI) and machine learning (ML) systems are increasingly used in medicine to improve clinical decision-making and healthcare delivery. In gastroenterology and hepatology, studies have explored a myriad of opportunities for AI/ML applications which are already making the transition to bedside. Despite these advances, there is a risk that biases and health inequities can be introduced or exacerbated by these technologies. If unrecognised, these technologies could generate or worsen systematic racial, ethnic and sex disparities when deployed on a large scale. There are several mechanisms through which AI/ML could contribute to health inequities in gastroenterology and hepatology, including diagnosis of oesophageal cancer, management of inflammatory bowel disease (IBD), liver transplantation, colorectal cancer screening and many others. This review adapts a framework for ethical AI/ML development and application to gastroenterology and hepatology such that clinical practice is advanced while minimising bias and optimising health equity.

Celiac disease: clinical update.

PURPOSE OF REVIEW: This review highlights literature from the past year and explores the impact on current understanding of celiac disease pathogenesis, diagnosis, and management. RECENT FINDINGS: In contrast to earlier clinical trials, recent data suggests that early gluten introduction may protect against the development of celiac disease. Celiac disease is underdiagnosed, associated with high burden of disease and linked to excess mortality risk, yet, there remains considerable uncertainty regarding the utility of mass screening in asymptomatic individuals. The gut microbiome is increasingly implicated in celiac disease pathogenesis, although the exact mechanism is undefined. Probiotics have been proposed as a disease-modifying option for celiac disease but most studies assessing efficacy are of low-quality. Patients with celiac disease do not appear to be at increased risk of contracting or developing adverse outcomes from COVID-19. Little is known about the pathogenesis of nonceliac gluten sensitivity; however, recent findings suggest an autoimmune basis for the condition. SUMMARY: Current understanding of celiac disease continues to advance, though significant knowledge gaps remain. Large, rigorous, prospectively designed studies are needed to further characterize celiac disease pathogenesis, management and therapeutic options.

An International Reporting Registry of Patients With Celiac Disease and COVID-19: Initial Results From SECURE-CELIAC.

Surveillance Epidemiology Under Research Exclusion for Celiac Disease (SECURE-CELIAC) is an international, de-identified adult and pediatric database created to monitor and report on the severity of coronavirus disease 2019 (COVID-19) outcomes in patients with celiac disease (CD).

Impact of a Citywide Benchmarking Intervention on Colonoscopy Quality Performance.

INTRODUCTION: There is marked variability in colonoscopy quality, limiting its effectiveness in colorectal cancer prevention. Multiple indicators have been established as markers for colonoscopy quality; however, there are conflicting data on the effects of quality reporting programs on endoscopist performance. In this study, we investigate the impact of a multicenter quarterly report card initiative on colonoscopy quality metric performance. METHODS: Data were collected from 194 endoscopists at 10 participating sites throughout New York City using a Qualified Clinical Data Registry from January 2013 to December 2014. Adenoma detection rate (ADR), cecal intubation rate, withdrawal time, bowel preparation quality and appropriate interval recommendations were tracked. Report cards were distributed to each site on a quarterly basis and technical assistance was provided as needed. Performance trends were analyzed using the Cochran-Armitage trend and analysis of variance tests. RESULTS: 37,258 screening colonoscopies were performed during the study period. There was a positive performance trend for ADR over time from the first quarter of 2013 to the last quarter of 2014 (15.6-25.7%; p < 0.001). There were also increases in cecal intubation rates (78.2-92.6%; p < 0.001), bowel preparation adequacy rates (77.5-92.8%; p < 0.001), and adherence to appropriate screening intervals (28.0-55.0%; p < 0.001). There was no clinically significant change in mean withdrawal time. CONCLUSIONS: The implementation of a quarterly report card initiative resulted in statistically significant improvements in adenoma detection, cecal intubation, bowel preparation adequacy rates, and appropriate recommended screening intervals.

Temporal Trends and Risk Factors for Postcolonoscopy Colorectal Cancer.

BACKGROUND: Colonoscopy is effective for colorectal cancer (CRC) prevention, yet patients may develop CRC despite adhering to screening/surveillance intervals. There are limited data on predictive factors associated with these postcolonoscopy CRCs (PCCRCs). We aimed to measure PCCRC rates and identify risk factors for PCCRC. METHODS: We performed a case-control study, comparing patients with PCCRCs to spontaneous CRCs diagnosed during a 12.5-year period at an academic medical center. PCCRCs were defined as CRCs diagnosed in between guideline-recommended screening/surveillance intervals. RESULTS: During the 12.5-year period, of 1266 CRCs diagnosed, 122 (10%) were PCCRCs. 70% of PCCRCs were diagnosed within 5 years of a prior colonoscopy. There was an increasing trend for PCCRC rates in recent years [odds ratio (OR), 2.78; 95% confidence interval (CI), 1.51-5.09], with PCCRCs comprising 13.6% of cancers diagnosed in 2016 as compared with 5.7% of cancers diagnosed in 2005. Older age (OR per year, 1.02; 95% CI, 1.01-1.04), proximal colonic location (OR, 1.99; 95% CI, 1.20-3.33) and early stage (OR, 2.57; 95% CI, 1.34-4.95) were associated with PCCRCs. In total, 41% of PCCRCs were diagnosed by a different physician from the physician who did the prior colonoscopy, and 42% of physicians did not diagnose any of their PCCRC cases. CONCLUSIONS: PCCRC rates are rising in recent years, likely reflecting the widespread adoption of colonoscopy as a primary screening tool, and are more common in older patients and those with proximal, early-stage tumors. The finding that a large proportion of PCCRCs are diagnosed by a different physician raises the concern that physicians are unaware of their own patients' PCCRCs.

Dual optical recordings for action potentials and calcium handling in induced pluripotent stem cell models of cardiac arrhythmias using genetically encoded fluorescent indicators.

Reprogramming of human somatic cells to pluripotency has been used to investigate disease mechanisms and to identify potential therapeutics. However, the methods used for reprogramming, in vitro differentiation, and phenotyping are still complicated, expensive, and time-consuming. To address the limitations, we first optimized a protocol for reprogramming of human fibroblasts and keratinocytes into pluripotency using single lipofection and the episomal vectors in a 24-well plate format. This method allowed us to generate multiple lines of integration-free and feeder-free induced pluripotent stem cells (iPSCs) from seven patients with cardiac diseases and three controls. Second, we differentiated human iPSCs derived from patients with Timothy syndrome into cardiomyocytes using a monolayer differentiation method. We found that Timothy syndrome cardiomyocytes showed slower, irregular contractions and abnormal calcium handling compared with the controls. The results are consistent with previous reports using a retroviral method for reprogramming and an embryoid body-based method for cardiac differentiation. Third, we developed an efficient approach for recording the action potentials and calcium transients simultaneously in control and patient cardiomyocytes using genetically encoded fluorescent indicators, ArcLight and R-GECO1. The dual optical recordings enabled us to observe prolonged action potentials and abnormal calcium handling in Timothy syndrome cardiomyocytes. We confirmed that roscovitine rescued the phenotypes in Timothy syndrome cardiomyocytes and that these findings were consistent with previous studies using conventional electrophysiological recordings and calcium imaging with dyes. The approaches using our optimized methods and dual optical recordings will improve iPSC applicability for disease modeling to investigate mechanisms underlying cardiac arrhythmias and to test potential therapeutics.