Esophagogastroduodenoscopy findings that do no not explain dysphagia are associated with underutilization of high-resolution manometry.

In patients with dysphagia that is not explained by upper endoscopy, high-resolution esophageal manometry (HRM) is the next logical step in diagnostic testing. This study investigated predictors of failure to refer for HRM after an upper endoscopy that was performed for but did not explain dysphagia. This was a retrospective cohort study of patients >18 years of age who underwent esophagogastroduodenoscopy (EGD) for dysphagia from 2015 to 2021. Patients with EGD findings that explained dysphagia (e.g. esophageal mass, eosinophilic esophagitis, Schatzki ring, etc.) were excluded from the main analyses. The primary outcome was failure to refer for HRM within 1 year of the index non-diagnostic EGD. We also investigated delayed referral for HRM, defined as HRM performed after the median. Multivariable logistic regression modeling was used to identify risk factors that independently predicted failure to refer for HRM, conditioned on the providing endoscopist. Among 2132 patients who underwent EGD for dysphagia, 1240 (58.2%) did not have findings to explain dysphagia on the index EGD. Of these 1240 patients, 148 (11.9%) underwent HRM within 1 year of index EGD. Endoscopic findings (e.g. hiatal hernia, tortuous esophagus, Barrett's esophagus, surgically altered anatomy not involving the gastroesophageal junction, and esophageal varices) perceived to explain dysphagia were independently associated with failure to refer for HRM (adjusted odds ratio 0.45, 95% confidence interval 0.25-0.80). Of the 148 patients who underwent HRM within 1 year of index EGD, 29.7% were diagnosed with a disorder of esophagogastric junction outflow, 17.6% with a disorder of peristalsis, and 2.0% with both disorders of esophagogastric outflow and peristalsis. The diagnosis made by HRM was similar among those who had incidental EGD findings that were non-diagnostic for dysphagia compared with those who had completely normal EGD findings. Demographic factors including race/ethnicity, insurance type, and income were not associated with failure to refer for HRM or delayed HRM. Patients with dysphagia and endoscopic findings unrelated to dysphagia have a similar prevalence of esophageal motility disorders to those with normal endoscopic examinations, yet these patients are less likely to undergo HRM. Provider education is indicated to increase HRM referral in these patients.

Antibiotic use and colorectal neoplasia: a systematic review and meta-analysis.

BACKGROUND AND AIMS: Colorectal cancer (CRC) is the third most common cancer for women and men and the second leading cause of cancer death in the USA. There is emerging evidence that the gut microbiome plays a role in CRC development, and antibiotics are one of the most common exposures that can alter the gut microbiome. We performed a systematic review and meta-analysis to characterise the association between antibiotic use and colorectal neoplasia. METHODS: We searched PubMed, EMBASE, and Web of Science for articles that examined the association between antibiotic exposure and colorectal neoplasia (cancer or adenoma) through 15 December 2019. A total of 6031 citations were identified and 6 papers were included in the final analysis. We assessed the association between the level of antibiotic use (defined as number of courses or duration of therapy) and colorectal neoplasia using a random effects model. RESULTS: Six studies provided 16 estimates of the association between level of antibiotic use and colorectal neoplasia. Individuals with the highest levels of antibiotic exposure had a 10% higher risk of colorectal neoplasia than those with the lowest exposure (effect size: 1.10, 95% CI 1.01 to 1.18). We found evidence of high heterogeneity (I2=79%, p=0.0001) but not of publication bias. CONCLUSIONS: Higher levels of antibiotic exposure is associated with an increased risk of colorectal neoplasia. Given the widespread use of antibiotics in childhood and early adulthood, additional research to further characterise this relationship is needed.

The Association Between IGF-I and IGFBP-3 and Incident Diabetes in an Older Population of Men and Women in the Cardiovascular Health Study.

Context: Insulin-like growth factor-I (IGF-I) has structural and functional similarities to insulin and may play a role in glucose homeostasis, along with insulin-like growth factor binding protein-3 (IGFBP-3), which binds the majority of circulating IGF-I. Objective: To assess whether IGF-I and IGFBP-3 are associated with a higher risk of incident diabetes in older adults. Design: Participants in the Cardiovascular Health Study (n = 3133), a cohort of adults aged ≥65 years, were observed for 16 years (n = 3133) for the development of incident diabetes. Statistical models were fit separately for men and women because of interactions with sex (P interaction: IGF-I, 0.02; IGFBP-3, 0.009) and were adjusted for relevant covariates. Setting: General community. Participants: Older adults who were nondiabetic at baseline and who did not develop diabetes within the first year of follow-up. Interventions: Not applicable. Main Outcome Measure: Incident diabetes as measured by fasting plasma glucose (FPG) ≥126 mg/dL, non-FPG ≥200 mg/dL, use of pharmacological treatment of diabetes, or existence of two or more inpatient or three or more outpatient or (at least one inpatient and at least one outpatient) Centers for Medicare & Medicaid Services claims with the diagnostic International Classification of Diseases, Ninth Revision, Clinical Modification code of 250.xx. Results: In women, higher IGFBP-3 (hazard ratio tertile 3 vs tertile 1 = 2.30; 95% confidence interval, 1.55 to 3.40; P trend < 0.0001) was significantly associated with incident diabetes. Total IGF-I was not significantly associated with incident diabetes. In men, neither IGF-I nor IGFBP-3 was significantly associated with incident diabetes. Conclusions: We confirmed a previously reported association between circulating IGFBP-3 and diabetes risk in the older adult population, establishing that this association is present among women but could not be shown to be associated in men.

Insulinlike Growth Factor Binding Protein-1 and Ghrelin Predict Health Outcomes Among Older Adults: Cardiovascular Health Study Cohort.

Context: Multiple diseases may explain the association of the growth hormone/insulinlike growth factor-I (GH/IGF-I) axis with longevity. Objective: To relate circulating GH/IGF-I system protein levels with major health events. Design and Setting: This is a cohort study set in 4 US communities. Participants: Adults (N = 2268) 65 years and older free of diabetes and cardiovascular disease. Measurements: We assessed insulinlike growth factor binding protein-1 (IGFBP-1) and ghrelin in fasting and 2-hour oral glucose tolerance test (OGTT) blood samples, as well as fasting IGF-I and IGFBP-3. Hazard ratios for mortality and a composite outcome for first incident myocardial infarction, stroke, heart failure, hip fracture, or death were adjusted for sociodemographic, behavioral, and physiological covariates. Results: During 13,930 person-years of follow-up, 48.1% of individuals sustained one or more components of the composite outcome and 31.8% died. Versus the lowest quartiles, the highest quartiles of fasting and 2-hour ghrelin were associated with 27% higher (95% confidence interval [CI]: 6%, 53%) and 39% higher (95% CI: 14%, 71%) risks of the composite outcome, respectively. The highest quartile of 2-hour IGFBP-1 was associated with 35% higher (95% CI: 1%, 52%) risk of the composite end point. Similarly, higher mortality was significantly associated with higher fasting and 2-hour ghrelin levels and with 2-hour IGFBP-1 level. When examined together, 2-hour post-OGTT levels of IGFBP-1 and ghrelin tended to predict outcomes better than fasting levels. Conclusions: Circulating IGFBP-1 and ghrelin measured during an OGTT predicted major health events and death in older adults, which may explain the influence of the GH/IGF-I axis on lifespan and health.

Agreement between circulating IGF-I, IGFBP-1 and IGFBP-3 levels measured by current assays versus unavailable assays previously used in epidemiological studies.

OBJECTIVE: Levels of insulin-like growth factor (IGF) proteins are associated with the risk of cancer and mortality. IGF assays produced by Diagnostic Systems Laboratories (DSL) were widely used in epidemiological studies, were not calibrated against recommended standards and are no longer commercially available. DESIGN: In a split sample study among 1471 adults participating in the Cardiovascular Health Study, we compared values obtained using DSL assays with alternative assays for serum IGF-I (Immunodiagnostic Systems, IDS), IGFBP-1 (American Laboratory Products Company, ALPCO) and IGFBP-3 (IDS). RESULTS: Results were compared using kernel density estimation plots, quartile analysis with weighted kappa statistics and linear regression models to assess the concordance of data from the different assays. Participants had a mean age of 77years. Results between alternative assays were strongly correlated (IGF-I, r=0.93 for DSL versus IDS; log-IGFBP-1, r=0.90 for DSL versus ALPCO; IGFBP-3, r=0.92 for DSL versus IDS). Cross tabulations showed that participants were usually in the same quartile categories regardless of the assay used (overall agreement, 74% for IGF-I, 64% for IGFBP-1, 71% for IGFBP-3). Weighted kappa also showed substantial agreement between assays (kw, 0.78 for IGF-I, 0.69 for IGFBP-1, 0.76 for IGFBP-3). Regressions of levels obtained with DSL assays (denoted X) to alternative assays were, IGF-I: 0.52X+15.2ng/ml, log-IGFBP-1: 1.01X-1.73ng/ml IGFBP-3: 0.87X+791.1ng/ml. Serum values of IGF-I, IGFBP-1 and IGFBP-3 measured using alternative assays are moderately correlated. CONCLUSIONS: Care is needed in the interpretation of data sets involving IGF analytes if assay methodologies are not uniform.

Changes in insulin-like growth factor-I and its binding proteins are associated with diabetes mellitus in older adults.

OBJECTIVES: To determine whether changes in insulin-like growth factor (IGF) protein levels are greater in participants with type 2 diabetes mellitus or worsening glycemia than in normoglycemic individuals over a 9-year follow-up period. DESIGN: Retrospective analysis of a cohort study. SETTING: Participants were recruited from North Carolina, California, Maryland, and Pennsylvania. PARTICIPANTS: Cardiovascular Health Study All Stars participants, a cohort study of community-dwelling adults aged 65 and older (N=897). MEASUREMENTS: Plasma IGF-I, IGF binding protein (IGFBP)-1, and IGFBP-3 levels were assessed and American Diabetes Association cut-points for impaired glucose tolerance (IGT), impaired fasting glucose (IFG), and diabetes mellitus were used to classify participants at baseline (1996-97) and follow-up (2005-06). RESULTS: At baseline, mean age was 76.3±3.6, and 18.5% had diabetes mellitus. Participants with IFG alone and IGT plus IFG had higher IGF-I levels and lower IGFBP-1 levels than those with normoglycemia or diabetes mellitus. The greatest percentage change in IGF levels occurred in those who had diabetes mellitus at baseline (9-year changes: -9.3% for IGF-I, 59.7% for IGFBP-1, -13.4% for IGFBP-3), the smallest in individuals who remained normoglycemic at follow-up (9-year changes: -3.7% for IGF-I, 25.6% for IGFBP-1, -6.4% for IGFBP-3), and intermediate in those who were normoglycemic but developed IFG at follow-up. CONCLUSION: Degrees of glycemic impairment are associated with varying degrees of change in IGF protein levels. The changes observed in the diabetes mellitus group have been previously shown to be associated with heart failure, cancer, and noncancer mortality.