Quantified Metrics of Gastric Emptying Delay by GLP-1 Agonists: A Systematic Review and Meta-Analysis with Insights for Periprocedural Management.

INTRODUCTION: Divergent recommendations for periprocedural management of GLP-1 receptor agonist (GLP-1 RA) medications rely on limited evidence. We performed a systematic review and meta-analysis to provide quantitative measures of gastric emptying relevant to mechanisms of weight loss and to periprocedural management of GLP-1 RA. We hypothesized that the magnitude of gastric emptying delay would be low and of limited clinical significance to procedural sedation risks. METHODS: A protocolized search identified studies on GLP-1 RA that quantified gastric emptying measures. Pooled estimates using random effects were presented as weighted mean difference with 95% confidence intervals (CI). Univariate meta-regression was performed to assess the influence of GLP-1 RA type, short- vs long-acting mechanism of action, and duration of treatment on gastric emptying. RESULTS: Fifteen studies met inclusion criteria. Five studies (n=247) utilized scintigraphy (GES). Mean T1/2 was 138.4 minutes (CI:74.5-202.3) for GLP-1 RA versus 95.0 minutes (CI:54.9-135.0) for placebo, with pooled mean difference of 36.0 minutes (CI:17.0-55.0, p<0.01, I2=79.4%). Ten studies (n=411) utilized the acetaminophen absorption test (AAT), with no significant delay in gastric emptying measured by Tmax, AUC4hr, and AUC5hr with GLP-1 RA (p>0.05). On meta-regression, type of GLP-1 RA, mechanism of action, and treatment duration did not impact gastric emptying (p>0.05). CONCLUSIONS: While a gastric emptying delay of ∼36 minutes is quantifiable on GLP-1 RA medications, it is of limited magnitude relative to standard periprocedural fasting periods. There were no substantial differences in gastric emptying on modalities reflective of liquid emptying (AAT), particularly at time points relevant to periprocedural care.

Centrally Distributed Adiposity as a Modifiable Risk Factor for Fecal Incontinence: U.S. Population-Based Analysis.

BACKGROUND AND AIMS: Fecal incontinence (FI) is highly prevalent with substantial impacts on quality of life and healthcare utilization. The impact of obesity on FI remains unclear, with differing conclusions using BMI as risk factor. We aimed to determine the association between obesity and FI, and whether this relationship is dependent on the distribution of adiposity (waist circumference-to-height ratio, WHtR). METHODS: This was a population-based analysis of the National Health and Nutrition Examination Survey, including participants who responded to the bowel health survey in 2005-2010. FI was defined by the accidental bowel leakage of solid stool, liquid, or mucus at least once in the past month. Stepwise multivariable logistic regression models were constructed to assess risk factors for FI. RESULTS: A total of 7,606 participants were included, with an overall FI prevalence of 9.2%. When stratified by quartiles of body measurements, FI was increasingly prevalent from 1st to 4th quartile for both WHtR (range: 5.3%-12.5%) and BMI (range: 7.1%-10.5%). WHtR was associated with FI and was a stronger predictor than BMI in all quartiles of body measurement. On multivariable analysis, WHtR remained a significant predictor of FI comparing the 4th to the 1st quartile of body measurements (OR:1.77, CI:1.11-2.80, p=0.017), whereas BMI was not. A WHtR cutoff of >0.592 optimized the Youden index in prediction of FI in the overall sample. CONCLUSION: WHtR was independently associated with increased odds of FI in this nationally representative sample of US adults, whereas BMI was not consistently correlated. This suggests bowel continence may depend more on how body mass is distributed.

Obesity Is Associated with Altered Rectal Sensitivity in Chronic Constipation.

BACKGROUND: Defecation dysfunction may contribute to chronic constipation (CC), but the impact of obesity on anorectal physiology in CC remains unclear. We aimed to evaluate the relationship between obesity and anorectal function on physiologic testing in patients presenting with CC. METHODS: This was a retrospective cohort study of consecutive adults who underwent high resolution anorectal manometry (HRAM) at a tertiary center for CC. Patient demographics, clinical history, surgical/obstetric history, medications, and HRAM results were reviewed. Patients were classified into obese (BMI > 30 kg/m2) vs non-obese (BMI < 30 kg/m2) groups at the time of HRAM. Fisher-exact/student t-test for univariate analyses and general linear regression for multivariable analysis were performed. RESULTS: 383 adults (mean 50.3 years; 85.8% female) with CC were included. On HRAM, patients with obesity had lower anal sphincter resting tone (37.3 vs 48.5 mmHg, p = 0.005) and maximum squeeze pressure (104.8 mmHg vs 120.0 mmHg, p = 0.043). No significant differences in dyssynergia (61% vs 53%, p = 0.294) and failed balloon expulsion (18% vs 25%, p = 0.381) were found between obese and non-obese groups. On balloon distention testing, the maximum tolerated (163.5 vs 147.6 mL, p = 0.042) and urge sensation (113.9 vs 103.7 mL, p = 0.048) volumes were significantly increased among patients with obesity. After adjusting for potential confounders, obesity remained independently associated with increased maximum tolerated volume (ß-coefficient 13.7, p = 0.049). CONCLUSION: Obesity was independently associated with altered rectal sensitivity among patients with CC. Altered rectal sensation may play an important role in CC among patients with obesity. Anorectal physiology testing should be considered to understand the pathophysiology and guide management.

Higher obesity class is associated with more severe esophageal symptoms and reflux burden but not altered motor function or contractile reserve.

BACKGROUND: Patients with obesity often report esophageal symptoms, with abnormal reflux and esophageal motility suggested as potential mechanisms. However, prior studies showed varying results, often limited by study design/size and esophageal function/symptom measures utilized. We aimed to examine the relationship between obesity and objective esophageal function testing and patient-reported outcomes, utilizing prospective symptom, manometric and reflux monitoring data with impedance. METHODS: Adults referred for high-resolution impedance-manometry (HRiM) and multichannel intraluminal impedance-pH monitoring (MII-pH) to evaluate esophageal symptoms were enrolled. Validated symptom and health-related quality of life (HR-QOL) instruments were prospectively collected: GERDQ, reflux symptoms index (RSI), dominant symptom intensity (DSI, multiplied 5-point Likert scales for symptom frequency/severity), global symptom severity (GSS, 100-point visual analog scale), and Short Form-12 (SF-12) for HR-QOL. Esophageal function testing measures were compared across body mass index (BMI) categories and correlated with patient-reported outcomes. KEY RESULTS: Seven hundred and fifty four patients were included (Normal:281/Overweight:253/Class I obesity:137/Class II/III obesity:83). Reflux burden measures on MII-pH (acid exposure time, total reflux episodes, bolus exposure time), conclusive pathologic reflux (Lyon), and hiatal hernia were increased in higher obesity classes compared to normal BMI. Class II/III obesity was associated with more normal/hypercontractile swallows, less ineffective swallows, and better bolus transit on HRiM. BMI correlated positively with GERDQ/RSI/DSI/GSS, and negatively with physical component score (SF-12). Esophageal symptom severity and HR-QOL correlated strongly with MII-pH findings, but not HRiM measures. CONCLUSIONS/INFERENCES: Obesity is associated with increased esophageal symptom burden and worse physical HR-QOL, which correlate with higher acid/bolus reflux burden but not altered esophageal motility/transit/contractile reserve.

Ineffective esophageal motility is associated with acute rejection after lung transplantation independent of gastroesophageal reflux.

BACKGROUND: Gastroesophageal reflux is associated with poorer outcomes after lung transplant, likely through recurrent aspiration and allograft injury. Although prior studies have demonstrated a relationship between impedance-pH results and transplant outcomes, the role of esophageal manometry in the assessment of lung transplant patients remains debated, and the impact of esophageal dysmotility on transplant outcomes is unclear. Of particular interest is ineffective esophageal motility (IEM) and its associated impact on esophageal clearance. AIM: To assess the relationship between pre-transplant IEM diagnosis and acute rejection after lung transplantation. METHODS: This was a retrospective cohort study of lung transplant recipients at a tertiary care center between 2007 and 2018. Patients with pre-transplant anti-reflux surgery were excluded. Manometric and reflux diagnoses were recorded from pre-transplant esophageal function testing. Time-to-event analysis using Cox proportional hazards model was applied to evaluate outcome of first episode of acute cellular rejection, defined histologically per International Society of Heart and Lung Transplantation guidelines. Subjects not meeting this endpoint were censored at time of post-transplant anti-reflux surgery, last clinic visit, or death. Fisher's exact test for binary variables and student's t-test for continuous variables were performed to assess for differences between groups. RESULTS: Of 184 subjects (54% men, mean age: 58, follow-up: 443 person-years) met criteria for inclusion. Interstitial pulmonary fibrosis represented the predominant pulmonary diagnosis (41%). During the follow-up period, 60 subjects (33.5%) developed acute rejection. The all-cause mortality was 16.3%. Time-to-event univariate analyses demonstrated significant association between IEM and acute rejection [hazard ratio (HR): 1.984, 95%CI: 1.03-3.30, P = 0.04], confirmed on Kaplan-Meier curve. On multivariable analysis, IEM remained independently associated with acute rejection, even after controlling for potential confounders such as the presence of acid and nonacid reflux (HR: 2.20, 95%CI: 1.18-4.11, P = 0.01). Nonacid reflux was also independently associated with acute rejection on both univariate (HR: 2.16, 95%CI: 1.26-3.72, P = 0.005) and multivariable analyses (HR: 2.10, 95%CI: 1.21-3.64, P = 0.009), adjusting for the presence of IEM. CONCLUSION: Pre-transplant IEM was associated with acute rejection after transplantation, even after controlling for acid and nonacid reflux. Esophageal motility testing may be considered in lung transplant to predict outcomes.

Low Prevalence of Extraesophageal Gastrointestinal Pathology in Patients with Eosinophilic Esophagitis.

BACKGROUND: Limited data are available to support current guidelines recommendations on obtaining gastric and duodenal biopsies of patients with clinical and histologic manifestations consistent with eosinophilic esophagitis (EoE) to rule out eosinophilic gastritis (EG) or duodenitis (EoD). Our study examined the prevalence of concomitant extraesophageal, gastrointestinal pathology to better characterize the diagnostic yield of additional biopsies. METHODS: This was a single-center, retrospective study which utilized ICD 9 codes (530.13) and search queries of pathology reports ("Eosinophilic esophagitis," "EoE") to identify EoE patients. Patient endoscopy reports, pathology reports, and office notes were manually reviewed to characterize cases. RESULTS: The electronic health record search yielded 1,688 EoE adults. In those who had extra-esophageal biopsies obtained, EG was identified in 34 (3.4%), H. pylori in 45 (4.6%), EoD in 27 (3.3%), and histology consistent with celiac disease in 20 (2.5%). Endoscopic abnormalities were found in the stomach of 92% of patients with EoE and EG and in the duodenum of 50% of patients with EoE and EoD. Symptoms of dyspepsia and/or abdominal pain occurred in a significantly greater proportion of patients with extraesophageal disease (64% vs. 19% in EoE group, p < 0.001). Overall, extraesophageal pathology would have been missed in 1.4% of patients lacking either symptoms or endoscopic signs suggestive of extraesophageal disease. CONCLUSIONS: The yield of gastric and duodenal biopsies in adults with EoE is low, with 6.5% of patients demonstrating histologic features of celiac disease, Helicobacter pylori, EG, and/or EoD. Biopsies of extraesophageal, gastrointestinal sites in patients with suspected or previously diagnosed EoE should consider symptom and endoscopy manifestations as well as the potential impact of histopathologic findings on clinical management.

Acute Hepatitis A and Hepatitis B Coinfection.

Hepatitis A (HAV) has emerged in outbreaks across the United States particularly in at-risk populations such as men who have sex with men, as well as patients with a history of drug use, homelessness, and incarceration. Immunization among these high-risk populations remains underused. In this study, we describe a case of acute HAV and hepatitis B (HBV) coinfection in an MSM patient occurring in the period of these outbreaks. Clinical resolution of acute HAV and HBV coinfection was attained by 5 months from the time of initial hospitalization without viral hepatitis treatment. This case highlights the need for increased awareness of at-risk populations for HAV and HBV infection in promoting guideline-based vaccination efforts.

Taxane-Induced Upper Gastrointestinal Bleeding.

Docetaxel is a taxane, which is a class of chemotherapy agent used in the treatment of multiple malignancies. It is known to have gastrointestinal side effects which can range from mild symptoms such as nausea and diarrhea to more severe complications such as neutropenic enterocolitis. In the current literature, taxanes have not been described to cause upper gastrointestinal bleeding and melena. Here, we present a case of a 54-year-old woman with breast cancer who developed dizziness, fatigue, and melena after receiving chemotherapy. Esophagogastroduodenoscopy revealed diffuse gastric erosions as well as ulceration and linear superficial lesions in the duodenum; biopsies from these sites showed taxane-induced toxicity. Her bleeding resolved with medical therapy and subsequent removal of docetaxel from her chemotherapy regimen. This case identifies upper gastrointestinal bleeding as a previously undescribed side effect of docetaxel therapy. Recent docetaxel use should be included in the differential diagnosis for upper gastrointestinal bleed, and diagnosis should lead to consideration of cessation of docetaxel or substitution with another chemotherapeutic agent.

Comprehensive meta-analysis of randomized controlled trials of Lactated Ringer's versus Normal Saline for acute pancreatitis.

INTRODUCTION: Fluid resuscitation is the keystone of treatment for acute pancreatitis. Though clinical guidelines and expert opinions agree on large volume resuscitation, debate remains on the optimal fluid type. The most commonly used fluids are Lactated Ringer's (LR) and Normal Saline (NS), but the studies published to date comparing LR vs NS yield conflicting results. We aimed to identify and quantitatively synthesize existing high quality data of the topic of fluid type or acute pancreatitis resuscitation. METHODS: In collaboration with the study team, an information specialist performed a comprehensive literature review to identify reports addressing type of fluid resuscitation. Studies were screened using the Covidence system by two independent reviewers in order to identify Randomized controlled trials comparing LR versus NS. The main outcome was the development of moderately severe or severe pancreatitis and additional outcomes included local complications, ICU admission, and length of stay. Pooled odds ratios were estimated using the random effects model and standardized mean difference to compare continuous variables. RESULTS: We reviewed 7964 abstracts and 57 full text documents. Four randomized controlled trials were identified and included in our meta-analyses. There were a total of 122 patients resuscitated with LR versus 126 with NS. Patients resuscitated with LR were less likely to develop moderately severe/severe pancreatitis (OR 0.49; 95 % CI 0.25-0.97). There was no difference in development of SIRS at 24 or 48 h or development of organ failure between the two groups. Patients resuscitated with LR were less likely to require ICU admission (OR 0.33; 95 % CI 0.13-0.81) and local complications (OR 0.42; 95 % CI 0.2-0.88). While there was a trend towards shorter hospitalizations for LR (SMD -0.18, 99 % CI -0.44-0.07), it was not statistically significant. CONCLUSION: Resuscitation with LR reduces the development of moderately severe-severe pancreatitis relative to NS. Nevertheless, no difference in SIRS development or organ failure underscores the need for further studies to verify this finding and define its mechanism.

Clinical outcomes of adults with eosinophilic esophagitis with severe stricture.

BACKGROUND AND AIMS: Eosinophilic esophagitis (EoE) is an inflammatory disease of the esophagus. Its prevalence has been increasing steadily over the past 3 decades. The prognosis of patients with EoE presenting with severe esophageal strictures is poorly understood. The aim of this study was to describe the clinical outcomes of patients with EoE with severe strictures and identify factors associated with a greater likelihood of improvement in esophageal diameter. METHODS: This study is a retrospective chart review of patients with EoE with severe stricture, defined as an esophageal diameter of 10 mm or less at one point in their disease course. Each patient's clinical course was followed during standard-of-care follow-up with medical or dietary therapy in conjunction with repeated esophageal dilation. Multivariate regression analysis was performed to determine which variables are associated with endoscopic response, defined by an improvement in esophageal diameter to 13 mm and to 15 mm. RESULTS: From a cohort of 1091 adults with EoE, severe strictures were identified in 66 patients (7%). Of the 66 patients, 59 (89%) achieved an esophageal diameter of ≥13 mm and 43 (65%) achieved ≥15 mm. Initial diameter (odds ratio, 1.58; 95% confidence interval, 1.06-2.35; P = .025) and histologic remission (odds ratio, 34.97; 95% confidence interval, 6.45-189.49; P < .0001) were significantly associated with achieving a diameter ≥15 mm. Age at diagnosis, gender, and number of months to maximum esophageal diameter were not associated with achieving either diameter. CONCLUSIONS: Most patients with EoE with severe stricture experienced improvement in esophageal diameter to ≥15 mm with treatment, suggesting that the currently available treatment options are effective for patients with severe strictures. The most significant factors associated with disease reversibility are initial esophageal diameter and histologic remission.

Treatment Gap in Primary Prevention Patients Presenting With Acute Coronary Syndrome.

Previous studies assessing healthcare provider compliance to the 2013 American College of Cardiology/American Heart Association (ACC/AHA) cholesterol guidelines indicate a significant underuse of statin therapy at appropriate intensity. However, data are limited in primary prevention patients. Our study aimed to evaluate the impact of the 2013 ACC/AHA guidelines through a retrospective analysis of primary prevention patients presenting with first time acute coronary syndrome (ACS). We retrospectively calculated the 10-year predicted Atherosclerotic Cardiovascular Disease (10yASCVD) risk in 1,265 patients ages 40 to 75 who presented with ACS and no previous ASCVD. In patients without known ambulatory systolic blood pressure, a multivariable linear regression model was used to predict outpatient systolic blood pressure. Outcomes analyzed in each 10yASCVD category included statin status and statin intensity (high/medium/low) with further categorization by type of ACS event and date of left heart catheterization. In both primary analysis and sensitivity analysis (patients with predicted systolic blood pressure), statistical significance was shown with respect to overall statin status, ST Elevation Myocardial Infarction, and date of left heart catheterization. In summary, retrospective calculation of 10yASCVD in patients with a first ACS event showed a significant number of ACS patients would have qualified for statin therapy per 2013 ACC/AHA guidelines before their event but had not been initiated on one.