Childhood and adolescent residential and farm pesticide exposures and inflammatory bowel disease incidence in a U.S. cohort of women.

BACKGROUND AND AIMS: There are few known risk factors for inflammatory bowel disease (IBD), an autoimmune disease characterized by chronic intestinal inflammation. Use of specific pesticides has been associated with higher incidence of IBD among pesticide applicators and their spouses, but no study has examined pesticide exposure in early life, a period where the human immune system undergoes rapid changes. We evaluated pesticide use during childhood and adolescence and incidence of IBD among US women enrolled in the Sister Study. METHODS: Incident IBD diagnoses between enrollment (2003-2009) and 2021 were identified and validated with medication use and colectomy/colostomy surgery. We estimated hazard ratios (HR) and 95 % confidence intervals (CI) for the relationship of childhood/adolescent residential and farm pesticide exposures with IBD incidence using Cox models, accounting for age, race and ethnicity, education, smoking, and birth year. RESULTS: We identified 277 incident IBD cases among 48,382 eligible participants. IBD hazard was elevated among those whose childhood residence was regularly treated with pesticides, especially among those who ever personally applied pesticides (HR = 1.39, 95%CI: 0.65, 2.99). We observed a positive association between IBD and exposure to broadcast pesticide sprays before DDT was banned (>6 times vs. never HR = 1.56, 95%CI: 1.06, 2.31). Among participants who lived on a farm during childhood/adolescence for ≥1 year (N = 9162), IBD hazards were higher among those who were in crop fields during pesticide application (HR = 2.06, 95%CI: 0.94, 4.51) and who ever personally applied pesticides on crops (HR = 1.85, 95%CI: 0.81, 4.18) or livestock (HR = 2.58, 95%CI: 1.14, 5.83). CONCLUSION: Early-life pesticide exposure may be a novel risk factor for IBD. Practices that reduce pesticide exposure during early life may help reduce the burden of this disease.

Glucagon-Like Peptide-1 Receptor Agonists Do Not Increase Aspiration During Upper Endoscopy in Patients With Diabetes.

BACKGROUND & AIMS: Glucagon-like peptide-1-receptor agonists (GLP1-RAs) have been associated with greater retention of gastric contents, however, there is minimal controlled, population-based data evaluating the potential adverse effects of GLP1-RA in the periprocedural setting. We aimed to determine if there is increased risk of aspiration and aspiration-related complications after upper endoscopy in patients using GLP1-RAs. METHODS: We used a nationwide commercial administrative claims database to conduct a retrospective cohort study of patients aged 18 to 64 with type 2 diabetes who underwent outpatient upper endoscopy from 2005 to 2021. We identified 6,806,046 unique upper endoscopy procedures. We compared claims for aspiration and associated pulmonary adverse events in the 14 days after upper endoscopy between users of GLP1-RAs, dipeptidyl peptidase 4 inhibitors (DPP4is), and chronic opioids. We adjusted for age, sex, Charlson Comorbidity score, underlying respiratory disease, and gastroparesis. RESULTS: We found that pulmonary adverse events after upper endoscopy are rare, ranging from 6 to 25 events per 10,000 procedures. When comparing GLP1-RAs with DPP4i, crude relative risks of aspiration (0.67; 95% CI, 0.25-1.75), aspiration pneumonia (0.95; 95% CI, 0.40-2.29), pneumonia (1.07; 95% CI, 0.62-1.86), or respiratory failure (0.75; 95% CI, 0.38-1.48) were not higher in patients prescribed a GLP1-RA. When comparing GLP1-RAs with opioids, crude relative risks were 0.42 (95% CI, 0.15-1.16) for aspiration, 0.60 (95% CI, 0.24-1.52) for aspiration pneumonia, 0.30 (95% CI, 0.19-0.49) for pneumonia, and 0.24 (95% CI, 0.13-0.45) for respiratory failure. These results were consistent across several sensitivity analyses. CONCLUSIONS: GLP1-RA use is not associated with an increased risk of pulmonary complications after upper endoscopy compared with DPP4i use in patients with type 2 diabetes.

Follow-Up of Microscopic Colitis Patients and Diarrhea Controls at 1 Year.

BACKGROUND AND AIMS: Microscopic colitis (MC) is a common cause of chronic diarrhea; however, the clinical course of this disease is poorly understood. We aimed to investigate how patients diagnosed with MC were treated in routine clinical practice and how their symptoms compared to patients with other causes of chronic diarrhea at one year follow-up. METHODS: We conducted a case-control study of patients undergoing outpatient colonoscopy to evaluate diarrhea. The study pathologist determined whether patients were classified as MC cases or non-MC controls. One year after colonoscopy, we interviewed cases (n = 74) and controls (n = 162) about their diagnosis, medications for diarrhea, and symptom burden. RESULTS: At 1-year follow-up after colonoscopy, 10% of MC cases were unaware of the diagnosis, 60% had been prescribed a medication for diarrhea, 40% had fecal urgency, 32% had weight loss, and 21% had fecal incontinence. Among cases, 46% were treated with budesonide. Compared to cases, controls had worse symptoms based on the Microscopic Colitis Disease Activity Index score with a median score of 3.0 (interquartile range 1.9-4.2) vs 2.3 (interquartile range 1.4-3.2) at 1-year follow-up. Controls had more frequent stools, urgency, fecal incontinence, and abdominal pain. CONCLUSION: In a cohort of patients with biopsy-confirmed MC and diarrhea controls, we found that some cases remained unaware of their diagnosis, many cases had persistent symptoms, and controls had worse symptoms than cases. These findings suggest there are opportunities to improve management of this chronic disease.

Follow-Up Colonoscopy for Detection of Missed Colorectal Cancer After Diverticulitis.

BACKGROUND & AIMS: Colonoscopy often is recommended after an episode of diverticulitis to exclude missed colorectal cancer (CRC). This is a controversial recommendation based on limited evidence. We estimated the prevalence and odds of CRC and advanced colorectal neoplasia on colonoscopy in patients with diverticulitis compared with CRC screening. METHODS: Using data from the Gastrointestinal Quality Improvement Consortium registry, we performed a cross-sectional study with patients ≥40 years old undergoing outpatient colonoscopy for an indication of diverticulitis follow-up evaluation or CRC screening. The primary outcome was CRC. The secondary outcome was advanced colorectal neoplasia. Odds ratios (ORs) and 95% CIs were calculated. RESULTS: We identified 4,591,921 outpatient colonoscopies performed for screening and 91,993 colonoscopies for diverticulitis follow-up evaluation. CRC prevalence was 0.33% in colonoscopies for screening and 0.31% in colonoscopies for diverticulitis. Compared with screening, patients with diverticulitis were less likely to have CRC (adjusted OR, 0.84; 95% CI, 0.74-0.94). CRC prevalence decreased to 0.17% in colonoscopies performed for diverticulitis only. Compared with screening, patients with diverticulitis as the only indication were less likely to have CRC (adjusted OR, 0.49; 95% CI, 0.36-0.68). CRC prevalence increased to 1.43% in patients with complicated diverticulitis. Compared with screening, patients with complicated diverticulitis were more likely to have CRC (adjusted OR, 3.57; 95% CI, 1.59-8.01). CONCLUSIONS: The risk of CRC cancer is low in most patients with diverticulitis. Patients with complicated diverticulitis are the exception. Our results suggest that colonoscopy to detect missed CRC should include diverticulitis patients with a complication and those not current with CRC screening.

Comprehensive Association Analyses of Extraintestinal Manifestations in Inflammatory Bowel Disease.

BACKGROUND & AIMS: Patients with inflammatory bowel disease (IBD) frequently develop extraintestinal manifestations (EIMs) that contribute substantially to morbidity. We assembled the largest multicohort data set to date to investigate the clinical, serologic, and genetic factors associated with EIM complications in IBD. METHODS: Data were available in 12,083 unrelated European ancestry IBD cases with presence or absence of EIMs (eg, ankylosing spondylitis [ankylosing spondylitis and sacroiliitis], primary sclerosing cholangitis [PSC], peripheral arthritis, and skin and ocular manifestations) across 4 cohorts (Cedars-Sinai Medical Center, National Institute for Diabetes and Digestive and Kidney Diseases IBD Genetics Consortium, Sinai Helmsley Alliance for Research Excellence Consortium, and Risk Stratification and Identification of Immunogenetic and Microbial Markers of Rapid Disease Progression in Children with Crohn's Disease cohort). Clinical and serologic parameters were analyzed by means of univariable and multivariable regression analyses using a mixed-effects model. Within-case logistic regression was performed to assess genetic associations. RESULTS: Most EIMs occurred more commonly in female subjects (overall EIM: P = 9.0E-05, odds ratio [OR], 1.2; 95% CI, 1.1-1.4), with CD (especially colonic disease location; P = 9.8E-09, OR, 1.7; 95% CI, 1.4-2.0), and in subjects who required surgery (both CD and UC; P = 3.6E-19, OR, 1.7; 95% CI, 1.5-1.9). Smoking increased risk of EIMs except for PSC, where there was a "protective" effect. Multiple serologic associations were observed, including with PSC (anti-nuclear cytoplasmic antibody; IgG and IgA, anti-Saccharomyces cerevisiae antibodies; and anti-flagellin) and any EIM (anti-nuclear cytoplasmic antibody; IgG and IgA, anti-Saccharomyces cerevisiae antibodies; and anti-Pseudomonas fluorescens-associated sequence). We identified genome-wide significant associations within major histocompatibility complex (ankylosing spondylitis and sacroiliitis, P = 1.4E-15; OR, 2.5; 95% CI, 2.0-3.1; PSC, P = 2.7E-10; OR, 2.8; 95% CI, 2.0-3.8; ocular, P = 2E-08, OR, 3.6; 95% CI, 2.3-5.6; and overall EIM, P = 8.4E-09; OR, 2.2; 95% CI, 1.7-2.9) and CPEB4 (skin, P = 2.7E-08; OR, 1.5; 95% CI, 1.3-1.8). Genetic associations implicated tumor necrosis factor, JAK-STAT, and IL6 as potential targets for EIMs. Contrary to previous reports, only 2% of our subjects had multiple EIMs and most co-occurrences were negatively correlated. CONCLUSIONS: We have identified demographic, clinical, and genetic associations with EIMs that revealed underlying mechanisms and implicated novel and existing drug targets-important steps toward a more personalized approach to IBD management.

Genetic and transcriptomic landscape of colonic diverticulosis.

OBJECTIVE: Colonic diverticulosis is a prevalent condition among older adults, marked by the presence of thin-walled pockets in the colon wall that can become inflamed, infected, haemorrhage or rupture. We present a case-control genetic and transcriptomic study aimed at identifying the genetic and cellular determinants underlying this condition and the relationship with other gastrointestinal disorders. DESIGN: We conducted DNA and RNA sequencing on colonic tissue from 404 patients with (N=172) and without (N=232) diverticulosis. We investigated variation in the transcriptome associated with diverticulosis and further integrated this variation with single-cell RNA-seq data from the human intestine. We also integrated our expression quantitative trait loci with genome-wide association study using Mendelian randomisation (MR). Furthermore, a Polygenic Risk Score analysis gauged associations between diverticulosis severity and other gastrointestinal disorders. RESULTS: We discerned 38 genes with differential expression and 17 with varied transcript usage linked to diverticulosis, indicating tissue remodelling as a primary diverticula formation mechanism. Diverticula formation was primarily linked to stromal and epithelial cells in the colon including endothelial cells, myofibroblasts, fibroblasts, goblet, tuft, enterocytes, neurons and glia. MR highlighted five genes including CCN3, CRISPLD2, ENTPD7, PHGR1 and TNFSF13, with potential causal effects on diverticulosis. Notably, ENTPD7 upregulation was confirmed in diverticulosis cases. Additionally, diverticulosis severity was positively correlated with genetic predisposition to diverticulitis. CONCLUSION: Our results suggest that tissue remodelling is a primary mechanism for diverticula formation. Individuals with an increased genetic proclivity to diverticulitis exhibit a larger numbers of diverticula on colonoscopy.

Racial Differences in Over-the-Counter Non-steroidal Anti-inflammatory Drug Use Among Individuals at Risk of Adverse Cardiovascular Events.

PURPOSE: Black Americans are disproportionately affected by adverse cardiovascular events (ACEs). Over-the-counter (OTC) non-steroidal anti-inflammatory drugs (NSAIDs) confer increased risk for ACEs, yet racial differences in the use of these products remain understudied. This study sought to determine racial differences in OTC NSAID and high-potency powdered NSAID (HPP-NSAID) use. METHODS AND MATERIALS: This retrospective analysis examined participants at risk of ACEs (defined as those with self-reported hypertension, diabetes, heart disease, or smoking history ≥ 20 years) from the North Carolina Colon Cancer Study, a population-based case-control study. We used multivariable logistic regression models to assess the independent associations of race with any OTC NSAID use, HPP-NSAID use, and regular use of these products. RESULTS: Of the 1286 participants, 585 (45%) reported Black race and 701 (55%) reported non-Black race. Overall, 665 (52%) reported any OTC NSAID use and 204 (16%) reported HPP-NSAID use. Compared to non-Black individuals, Black individuals were more likely to report both any OTC NSAID use (57% versus 48%) and HPP-NSAID use (22% versus 11%). In multivariable analyses, Black (versus non-Black) race was independently associated with higher odds of both NSAID use (OR 1.4, 95% CI (1.1, 1.8)) and HPP-NSAID use (OR 1.8 (1.3, 2.5)). CONCLUSIONS: Black individuals at risk of ACEs had higher odds of any OTC NSAID and HPP-NSAID use than non-Black individuals, after controlling for pain and socio-economic status. Further research is necessary to identify potential mechanisms driving this increased use.

Dietary Calcium and Risk of Microscopic Colitis.

BACKGROUND: Microscopic colitis (MC) is an increasingly common cause of watery diarrhea particularly in older individuals. The role of diet in MC has received little study. METHODS: We conducted a case-control study at a single institution enrolling patients referred for elective outpatient colonoscopy for diarrhea. Patients were classified as cases with MC or non-MC controls after a review of colon biopsies by 1 research pathologist. Study subjects were interviewed by a trained telephone interviewer using a validated food frequency questionnaire. Adherent microbes were evaluated from colonic biopsies using 16s rRNA sequencing. RESULTS: The study population included 106 cases with MC and 215 controls. Compared with controls, the cases were older, better educated, and more likely to be female. Cases with MC had lower body mass index and were more likely to have lost weight. Subjects in the highest quartile of dietary calcium intake had a lower risk of MC compared with those in the lowest quartile (adjusted odds ratio 0.22, 95% confidence interval 0.07-0.76). The findings were not explained by dairy intake, body mass index, or weight loss. We found that dietary calcium intake had significant associations with the abundance of Actinobacteria and Coriobacteriales in the microbial community of colonic biopsies. DISCUSSION: Compared with patients with diarrhea, cases with MC had a lower intake of dietary calcium. Diet can be associated with alterations in the gut microbiota and with luminal factors that could affect the risk of MC.

Genetic coding variant in complement factor B (CFB) is associated with increased risk for perianal Crohn's disease and leads to impaired CFB cleavage and phagocytosis.

OBJECTIVE: Perianal Crohn's disease (pCD) occurs in up to 40% of patients with CD and is associated with poor quality of life, limited treatment responses and poorly understood aetiology. We performed a genetic association study comparing CD subjects with and without perianal disease and subsequently performed functional follow-up studies for a pCD associated SNP in Complement Factor B (CFB). DESIGN: Immunochip-based meta-analysis on 4056 pCD and 11 088 patients with CD from three independent cohorts was performed. Serological and clinical variables were analysed by regression analyses. Risk allele of rs4151651 was introduced into human CFB plasmid by site-directed mutagenesis. Binding of recombinant G252 or S252 CFB to C3b and its cleavage was determined in cell-free assays. Macrophage phagocytosis in presence of recombinant CFB or serum from CFB risk, or protective CD or healthy subjects was assessed by flow cytometry. RESULTS: Perianal complications were associated with colonic involvement, OmpC and ASCA serology, and serology quartile sum score. We identified a genetic association for pCD (rs4151651), a non-synonymous SNP (G252S) in CFB, in all three cohorts. Recombinant S252 CFB had reduced binding to C3b, its cleavage was impaired, and complement-driven phagocytosis and cytokine secretion were reduced compared with G252 CFB. Serine 252 generates a de novo glycosylation site in CFB. Serum from homozygous risk patients displayed significantly decreased macrophage phagocytosis compared with non-risk serum. CONCLUSION: pCD-associated rs4151651 in CFB is a loss-of-function mutation that impairs its cleavage, activation of alternative complement pathway, and pathogen phagocytosis thus implicating the alternative complement pathway and CFB in pCD aetiology.

Alpha-Gal Sensitization in a US Screening Population Is Not Associated With a Decreased Meat Intake or Gastrointestinal Symptoms.

INTRODUCTION: Patients with alpha-gal syndrome, a delayed reaction to mammalian meat, can present with isolated gastrointestinal (GI) symptoms. We aimed to estimate the frequency of alpha-gal sensitization in a Southeastern US population and determine the association between sensitization and mammalian product dietary intake or GI symptoms. METHODS: We performed a cross-sectional study of participants who underwent a screening colonoscopy at our center between 2013 and 2015. We quantified serum alpha-gal immunoglobulin E antibodies in participants who were prospectively enrolled at screening colonoscopy and compared diet intake and lower GI symptoms reported in standardized questionnaires among those with elevated versus no alpha-gal IgE antibodies. RESULTS: Alpha-gal IgE antibodies were common-31.4% of screening colonoscopy participants (127 of 404) had elevated serum alpha-gal IgE >0.1 kU/L. Alpha-gal-sensitized participants endorsed similar rates of abdominal pain compared with those without alpha-gal antibodies (33% vs 38%, adjusted odds ratio 0.9, 95% confidence interval 0.7-1.3). Mammalian meat consumption did not differ based on alpha-gal sensitization status (average 1.43 servings/d in sensitized subjects vs 1.50 in alpha-gal IgE-negative subjects, P = 0.9). Alpha-gal-sensitized participants with levels ≥10 (n = 21) were overrepresented in the lowest quartiles of mammalian meat consumption, but not among those with GI symptoms in general. Participants with high alpha-gal antibody levels >2 kU/L (n = 45) or ≥10 U/L (n = 21) did not have a reduced mean daily mammalian meat intake compared with seronegative people. DISCUSSION: Elevated alpha-gal IgE antibodies were common and not associated with a reduced mammalian meat intake, abdominal pain, or diarrhea. Seropositivity did not predict symptomatic alpha-gal sensitization in this general screening population. Other host factors likely contribute to the phenotypic expression of alpha-gal syndrome.

Healthcare system engagement and algorithm-identified cancer incidence following initiation of a new medication.

PURPOSE: Implausibly high algorithm-identified cancer incidence within a new user study after medication initiation may result from increased healthcare utilization (HU) around initiation ("catch-up care") that increases diagnostic opportunity. Understanding the relationships between HU prior to and around initiation and subsequent cancer rates and timing is important to avoiding protopathic bias. METHODS: We identified a cohort of 417 458 Medicare beneficiaries (2007-2014) aged ≥66 initiating an antihypertensive (AHT) after ≥180 days of non-use. Initiators were stratified into groups of 0, 1, 2-3, and ≥4 outpatient visits (OV) 60-360 days before initiation. We calculated algorithm-identified colorectal cancer (aiCRC) rates stratified by OVs and time since AHT initiation: (0-90, 91-180, 181-365, 366-730, and 731+ days). We summarized HU -360/+60 days around AHT initiation by aiCRC timing: (0-29, 30-89, 90-179, and ≥180 days). RESULTS: AiCRC incidence (311 per 100 000 overall) peaked in the first 0-90 days, was inversely associated with HU before initiation, and stabilized ≥180 days after AHT initiation. Catch-up care was greatest among persons with aiCRCs identified <30 days in follow-up. Catch-up care magnitude decreased as time to the aiCRC date increased, with aiCRCs identified ≥180 days after AHT initiation exhibiting similar HU compared with the full cohort. CONCLUSION: Lower HU before-and increased HU around AHT initiation-seem to drive excess short-term aiCRC incidence. Person-time and case accrual should only begin when incidence stabilizes. When comparison groups within a study differ by HU, outcome-detection bias may exist. Similar observations may exist in other settings when typical HU is delayed (e.g., cancer screening during SARS-CoV-2).

Diverticulosis Is Associated With Internal Hemorrhoids on Colonoscopy: Possible Clues to Etiology.

Hemorrhoids are a common but poorly understood gastrointestinal condition.1 Bowel habits and fiber consumption are frequently cited as risk factors for hemorrhoids, but research has been inconclusive.2 Recent genome-wide association studies (GWAS) have suggested an association between diverticular disease and hemorrhoids.3 We sought to investigate the association between colonic diverticulosis and internal hemorrhoids to validate the prediction from the GWAS.

Development of an Inflammatory Bowel Disease-Specific Medication Adherence Instrument and Reasons for Non-adherence.

BACKGROUND: Medication adherence impacts disease control in inflammatory bowel disease (IBD). Existing adherence measures such as the Morisky Medication Adherence Scale 8© are often costly, non-medication-specific, and time-consuming. AIMS: We aimed to develop a non-proprietary, IBD-specific medication adherence instrument and to assess reasons for suboptimal medication adherence. METHODS: We developed the IBD Medication Adherence Tool to assess frequency of adherence and indications for missed or delayed medication doses. We co-administered the IBD Medication Adherence Tool and the Morisky Medication Adherence Scale 8© (licensed for use) to participants enrolled in an internet-based cohort of adults with IBD and taking least one daily, oral IBD medication. We used Spearman's correlation to evaluate associations between the IBD Medication Adherence Tool and Morisky Medication Adherence Scale 8©. We then categorized patients as sub-optimally adherent (IBD Medication Adherence Tool score 1-4) and highly adherent (score 5) and evaluated factors associated with and reasons for suboptimal adherence using multivariable analysis. RESULTS: We evaluated 514 patients (73% female, mean age 49), of whom 21.4% had suboptimal adherence. IBD Medication Adherence Tool scores were moderately correlated with Morisky Medication Adherence Scale 8© (r = 0.56, p < 0.001). The most commonly reported reasons for suboptimal adherence were forgetting, feeling well, and cost. Younger age and current smoking were associated with suboptimal adherence. CONCLUSIONS: We developed a non-proprietary, IBD-specific tool to assess adherence to IBD medications, validated in a cohort of patients with IBD on daily, oral medications. Common reasons for suboptimal IBD medication adherence include forgetting, feeling well, and cost.

Trimodality Therapy vs Definitive Chemoradiation in Older Adults With Locally Advanced Esophageal Cancer.

BACKGROUND: The comparative effectiveness of trimodality therapy vs definitive chemoradiation for treating locally advanced esophageal cancer in older adults is uncertain. Existing trials lack generalizability to older adults, a population with heightened frailty. We sought to emulate a hypothetical trial comparing these treatments using real-world data. METHODS: A cohort of adults aged 66-79 years diagnosed with locally advanced esophageal cancer between 2004 and 2017 was identified in the Surveillance Epidemiology and End Results-Medicare database. The clone-censor-weight method was leveraged to eliminate time-related biases when comparing outcomes between treatments. Outcomes included overall mortality, esophageal cancer-specific mortality, functional adverse events, and healthy days at home. RESULTS: A total of 1240 individuals with adenocarcinomas and 661 with squamous cell carcinomas were identified. For adenocarcinomas, the standardized 5-year risk of mortality was 73.4% for trimodality therapy and 83.8% for definitive chemoradiation (relative risk [RR] = 0.88, 95% confidence interval [CI] = 0.82 to 0.95). Trimodality therapy was associated with mortality risk reduction for squamous cell carcinomas (RR = 0.87, 95% CI = 0.70 to 1.01). The 1-year incidence of functional adverse events was higher in the trimodality group (adenocarcinomas RR = 1.40, 95% CI = 1.22 to 1.65; squamous cell carcinomas RR = 1.21, 95% CI = 1.00 to 1.49). Over 5 years, trimodality therapy was associated with 160 (95% CI = 67 to 229) and 177 (95% CI = 51 to 313) additional home days in individuals with adenocarcinomas and squamous cell carcinomas, respectively. CONCLUSIONS: Compared with definitive chemoradiation, trimodality therapy was associated with reduced mortality but increased risk of function-related adverse events. Discussing these tradeoffs may help optimize care plans.

Microbial Associations With Microscopic Colitis.

INTRODUCTION: Microscopic colitis is a relatively common cause of chronic diarrhea and may be linked to luminal factors. Given the essential role of the microbiome in human gut health, analysis of microbiome changes associated with microscopic colitis could provide insights into the development of the disease. METHODS: We enrolled patients who underwent colonoscopy for diarrhea. An experienced pathologist classified patients as having microscopic colitis (n = 52) or controls (n = 153). Research biopsies were taken from the ascending (ASC) and descending (DES) colon, and the microbiome was characterized with Illumina sequencing. We analyzed the associations between microscopic colitis and microbiome with a series of increasingly complex models adjusted for a range of demographic and health factors. RESULTS: We found that alpha diversity was significantly lower in cases with microscopic colitis compared with that in controls in the DES colon microbiome. In the DES colon, a series of models that adjusted for an increasing number of covariates found taxa significantly associated with microscopic colitis, including Proteobacteria that was enriched in cases and Collinsella that was enriched in controls. While the alpha diversity and taxa were not significantly associated with microscopic colitis in the ASC colon microbiome, the inference P values based on ASC and DES microbiomes were highly correlated. DISCUSSION: Our study demonstrates an altered microbiome in cases with microscopic colitis compared with that in controls. Because both the cases and controls experienced diarrhea, we have identified candidate taxa that could be mechanistically responsible for the development of microscopic colitis independent of changes to the microbial community caused by diarrhea.

Omega-3 Polyunsaturated Fatty Acids, Gut Microbiota, Microbial Metabolites, and Risk of Colorectal Adenomas.

Omega-3 polyunsaturated fatty acids (ω-3 PUFAs) are thought to protect against colorectal adenoma (CRA) development. We aimed to further understand the underlying mechanisms by examining the relationships between ω-3 PUFAs and the gut microbiota on CRAs. We assessed the mucosal microbiota via bacterial 16S rRNA sequencing among 217 CRA cases and 218 controls who completed PUFA intake questionnaires. The overall microbial composition was assessed by α-diversity measurements (diversity, richness, and evenness). Global metabolomics was conducted using a random subset of case−control pairs (n = 50). We compared microbiota and metabolite signatures between cases and controls according to fold change (FC). Odds ratios (OR) and confidence intervals (CI) were estimated from logistic regression for associations of ω-3 PUFAs and the microbiota with CRAs. We observed an inverse association between overall ω-3 PUFA intake and CRAs, especially for short-chain ω -3 PUFAs (OR = 0.45, 95% CI: 0.21, 0.97). Such inverse associations were modified by bacterial evenness (p-interaction = 0.03). Participants with higher levels (FC > 2) of bile acid-relevant metabolites were more likely to have CRAs than the controls, and the correlation between bile acids and bacterial diversity differed by case−control status. Our findings suggest that ω-3 PUFAs are inversely associated with CRA development, and the association may be modified by gut microbiota profiles.

Patterns of care amongst older adults diagnosed with locally advanced esophageal cancer: A cohort study.

INTRODUCTION: Since the early 2010s, neoadjuvant chemoradiation followed by esophagectomy (trimodal therapy) has been a recommended treatment for patients diagnosed with locally advanced esophageal cancer. However, it may also add treatment-related toxicity, particularly for older adults with significant comorbidity and frailty burdens. We examined contemporary patterns of care in older adults, which have not been well characterized. MATERIALS AND METHODS: We used the Surveillance Epidemiology and End Results-Medicare database to identify a cohort of US adults aged 66 years and older diagnosed with incident locally advanced esophageal cancer between 2004 and 2017. Calendar year age-standardized percentages of treatment receipt were calculated. Joinpoint regression was used to detect temporal trends in treatment receipt. Descriptive associations between patient factors and treatment were assessed. Trend analyses quantified how the percentage of trimodal and definitive chemoradiation (no surgery) patients receiving cisplatin-based, carboplatin-based, and other chemotherapy regimens evolved over time. RESULTS: In total, 4332 adults aged ≥66 years with locally advanced esophageal cancer were included. The age-standardized percentage of patients receiving trimodal therapy increased from 16.7% in 2004 to 26.1% in 2017 (annual percent change = 3.5%; 95% confidence interval [CI], 0.7%-6.4%) in adenocarcinomas and from 7.3% in 2004 to 9.1% in 2017 (annual percent change = 0.4%; 95% CI, -4.1%-5.1%) in squamous cell carcinomas. By 2017, definitive chemoradiation became the most frequently used treatment modality for adenocarcinomas (49.8%; 95% CI, 43.5-56.0) and squamous cell carcinomas (59.5%; 95% CI, 50.8-68.2). Patients with higher comorbidity and frailty burdens were less likely to be treated with trimodal therapy. Amongst patients receiving chemoradiation as part of their treatment, a large and swift channeling away from cisplatin and towards carboplatin-based regimens was observed. DISCUSSION: In practice, definitive chemoradiation is the most commonly received treatment by older adults with locally advanced esophageal cancer. Four out of five older adults do not receive trimodal therapy, some of whom are potentially undertreated.

Colonic Diverticulosis Is Not Associated With Painful Abdominal Symptoms in a US Population.

BACKGROUND AND AIMS: Symptomatic uncomplicated diverticular disease is a controversial diagnosis defined as chronic gastrointestinal symptoms in patients with diverticulosis. We assessed whether individuals with diverticulosis had an increased risk of abdominal pain, irritable bowel syndrome, or altered bowel habits. METHODS: We performed a prospective cohort study of participants who had a first-time screening colonoscopy at the University of North Carolina between 2013 and 2015. The colonoscopy included a detailed assessment for diverticulosis. Participants completed a follow-up interview between 2019 and 2020 to measure bowel habits and gastrointestinal symptoms. Poisson regression was used to estimate relative risk and 95% confidence intervals (CIs). RESULTS: Among the 310 participants, 128 (41%) had diverticulosis at baseline. Follow-up interviews were performed a mean of 6.8 years after the baseline colonoscopy. After adjustment for confounders, there was no association between diverticulosis and abdominal pain lasting >24 hours (relative risk [RR], 0.40; 95% CI, 0.05-3.45) or symptoms of irritable bowel syndrome (RR, 1.30; 95% CI, 0.69-2.42) at the time of follow-up. Compared to those with no diverticulosis, participants with diverticulosis were more likely to have more frequent bowel movements per day (RR, 1.60; 95% CI, 1.05-2.44). The association was stronger in participants with >10 diverticula (RR, 2.03; 95% CI, 1.19-3.48). Diverticulosis was not associated with altered stool consistency. CONCLUSION: These findings suggest that diverticulosis is associated with more frequent bowel movements contrary to the widespread belief that patients with diverticulosis are constipated. Diverticulosis was not associated with abdominal pain or symptoms of irritable bowel syndrome. The diagnosis of symptomatic uncomplicated diverticular disease must be reconsidered.