Risk factors associated with functional esophageal disorders (FED) versus gastroesophageal reflux disease (GERD).

INTRODUCTION: Despite the high prevalence of typical symptoms of gastroesophageal reflux disease (GERD), approximately 30% of patients have functional esophageal disorders (FED) on ambulatory reflux monitoring, which may include reflux hypersensitivity (RH; defined as physiologic acid exposure but temporally correlated symptoms of reflux), or functional heartburn (FH; defined as physiologic acid exposure and negative symptom correlation). There are limited epidemiological data characterizing these conditions. We investigated demographic and socioeconomic factors as well as medical comorbidities which may predispose to FED versus pathologic GERD. METHODS: Adult patients with reflux symptoms for at least 3 months were studied with 24-h pH-impedance testing from 11/2019 to 3/2021. Participants were categorized into pathologic GERD, FH, or RH using pH-impedance data and reported symptom correlation. Demographic data, including age, gender, race/ethnicity, zip code, insurance status, and medical comorbidity data were retrospectively retrieved from the electronic medical record on all participants. RESULTS: 229 patients were included. Non-Hispanic Asian ethnicity (OR 5.65; p = 0.01), underweight BMI (OR 7.33; p = 0.06), chronic pain (OR 2.33; p < 0.01), insomnia (OR 2.83; p = 0.06), and allergic rhinitis (OR 3.90; p < 0.01) were associated with a greater risk for FED. Overweight BMI (OR 0.48; p = 0.03) and alcohol use (OR 0.57; p = 0.06) were associated with a decreased risk for FED. DISCUSSION: This is the first report of a greater risk of FED in patients with underweight BMI, insomnia, chronic pain, allergic rhinitis, or of Asian or Hispanic ethnicities. The weak associations between female gender and anxiety are corroborated in other studies. Our findings enable clinicians to better screen patients with reflux for this disorder.

Manometric esophagogastric junction barrier metrics as predictors of gastroesophageal reflux.

BACKGROUND: High-resolution manometry (HRM) tools, like esophagogastric junction contractile integral (EGJ-CI), assess EGJ barrier function. GOALS: This study aimed to evaluate the relationships between manometric EGJ metrics with esophageal acid exposure. STUDY: We conducted a retrospective review of 284 patients who underwent HRM and ambulatory reflux testing between 11/2017-1/2020. EGJ-CI and total-EGJ-CI were manually calculated. Pathologic acid exposure was defined as pH < 4 with esophageal acid exposure time (EAET) exceeding 6.0%. Pearson's correlation, univariable and multivariable regression models were utilized to assess the relationships between pathologic acid exposure and EGJ parameters. Sensitivity and specificity thresholds for EGJ-CI and total EGJ-CI were optimized with ROC analyses. RESULTS: On univariable analysis, patients with pathologic acid exposure had increased odds of having lower mean basal LES pressures, EGJ-CI, and total EGJ-CI than patients without pathologic acid exposure. On multivariable analysis, age, EGJ-CI and mean DCI were significant predictors of pathologic acid exposure. There were significant, though weak, correlations between EAET and EGJ-CI and total EGJ-CI (r = - 0.18, - 0.19, p < 0.01, respectively). An EGJ-CI cutoff of 44.16 as a predictor for pathologic acid exposure had a sensitivity of 46% and specificity of 42% (AUC 0.60). Total EGJ-CI cutoff of 11,461.3 for pathologic acid exposure had a sensitivity of 44% and a specificity of 43% (AUC 0.62). CONCLUSION: EGJ-CI can independently predict pathologic acid exposure. However, the poor correlation between EGJ-CI and acid exposure, as well as the low sensitivity and specificity of calculated thresholds, indicate that mechanisms other than EGJ barrier function may impact acid exposure.

Body mass index and additional risk factors for cancer in adults with cystic fibrosis.

BACKGROUND: Adults with cystic fibrosis (CF) have an increased risk of a variety of cancers, notably gastrointestinal cancers. In CF higher body mass index (BMI) is associated with improved long-term outcomes, yet in the general population high BMI is associated with increased cancer risk. We aimed to delineate associations between BMI and other factors with cancer risk in adults with CF. METHODS: This was a retrospective cohort study using CF Foundation Patient Registry data from 1992 to 2015. Data were collected on age, sex, CFTR mutation class, pancreatic insufficiency, and annualized data on BMI and FEV1. The primary analysis was the association between BMI and cancer, with secondary analyses focused on BMI trajectory. Multivariable logistic regression was performed, with analyses stratified by history of transplant. RESULTS: Of 26,199 adults with CF, 446 (1.7%) had cancer diagnosed by histology at a mean age of 40.0 years (SD 12.2), with a higher proportion of transplanted patients developing cancer (137 (3.8%) v 309(1.4%), p < 0.001). Among non-transplanted patients, there was no association between BMI and cancer (p for trend = 0.43). Pancreatic insufficiency (p < 0.01) and higher FEV1 (p < 0.01) were associated with increased cancer risk. In transplanted patients, higher BMI was associated with reduced risk of cancer (p for trend = 0.04). Older age was associated with increased risk in both groups (p < 0.001). BMI trajectories were not associated with cancer risk in either group. CONCLUSION: Higher BMI is associated with a reduced risk of cancer in transplanted adults with CF. Pancreatic insufficiency is a risk factor for cancer in non-transplanted CF patients.

Factors Associated With Adherence to Helicobacter pylori Testing During Hospitalization for Bleeding Peptic Ulcer Disease.

BACKGROUND & AIMS: Guidelines recommend testing patients with peptic ulcer disease for Helicobacter pylori infection. We sought to identify factors associated with adherence to testing for H pylori in patients hospitalized for bleeding ulcers and to evaluate whether performing these tests affect risk for rebleeding. METHODS: We performed a retrospective study of 830 inpatients who underwent endoscopy from 2011 through 2016 for gastrointestinal bleeding from gastric or duodenal ulcers. We searched electronic medical records for evidence of tests to detect H pylori by biopsy, serologic, or stool antigen analyses. We used multivariable models to identify clinical, demographic, and endoscopic factors associated with testing for H pylori. Kaplan-Meier analysis was performed to determine whether H pylori testing altered risk for the composite outcome of rebleeding or death within 1 year of admission. RESULTS: Among the patients hospitalized for bleeding peptic ulcer disease during the 6-year period, 19% were not tested for H pylori within 60 days of index endoscopy. Hospitalization in the intensive care unit (ICU) was the factor most frequently associated with nonadherence to H pylori testing guidelines (only 66% of patients in the ICU were tested vs 90% of patients not in the ICU; P < .01), even after we adjusted for ulcer severity, coagulation status, extent of blood loss, and additional factors (adjusted odds ratio, 0.42; 95% CI, 0.27-0.66). Testing for H pylori was associated with a 51% decreased risk of rebleeding or death during the year after admission (adjusted hazard ratio 0.49; 95% CI, 0.36-0.67). CONCLUSIONS: In an analysis of hospitalized patients who underwent endoscopy for gastrointestinal bleeding from gastric or duodenal ulcers, we found admission to the ICU to be associated with failure to test for H pylori infection. Failure to test for H pylori was independently associated with increased risk of rebleeding or death within 1 year of hospital admission. We need strategies to increase testing for H pylori among inpatients with bleeding ulcers.

Patterns of Marijuana Use Among Patients With Celiac Disease in the United States: A Population-based Analysis of the NHANES Survey.

BACKGROUND: Marijuana use has been assessed in patients with chronic gastrointestinal disorders and may contribute to either symptoms or palliation. Use in those with celiac disease (CD) has not been assessed. Our aim was to evaluate patterns of marijuana use in a large population-based survey among patients with CD, people who avoid gluten (PWAG), and controls. STUDY: We analyzed data from the National Health and Nutrition Examination Survey from 2009 to 2014. χ tests and multivariable logistic regression were used to compare participants with CD and PWAG to controls regarding the use of marijuana. RESULTS: Among respondents who reported ever using marijuana (overall 59.1%), routine (at-least monthly) marijuana use was reported by 46% of controls versus 6% of participants with diagnosed CD (P=0.005) and 66% undiagnosed CD as identified on serology (P=0.098) and 51% of PWAG (P=0.536). Subjects with diagnosed CD had lower odds of routine marijuana use compared with controls (odds ratio, 0.08; 95% confidence interval, 0.01-0.73), whereas participants with undiagnosed CD had increased odds of routine use (odds ratio, 2.26; 95% confidence interval, 0.83-6.13), which remained elevated even after adjusting for age, sex, race/ethnicity, health insurance status, alcohol, tobacco use, educational level, and poverty/income ratio. CONCLUSIONS: In all groups, marijuana use was high. Although there were no differences among subjects with CD, PWAG, and controls who ever used marijuana, subjects with diagnosed CD appear to have decreased routine use of marijuana when compared with controls and PWAG. Those with undiagnosed CD have significantly higher rates of regular use. Future research should focus on the utilization of marijuana as it may contribute to further understanding of symptoms and treatments.

Clostridioides difficile infection and recurrence among 2622 solid organ transplant recipients.

BACKGROUND: Clostridioides difficile infection (CDI) is common after solid organ transplant (SOT) and is associated with high morbidity and mortality. METHODS: We assessed incidence, risk factors, and outcomes of CDI among SOT patients at a large multi-organ transplant center. Multivariable logistic regression was used to identify risk factors for initial and recurrent CDI. RESULTS: A total of 2622 SOT patients were included. 224 (8.5%) had CDI 1 year post-SOT. The highest incidence of CDI was among pancreas recipients (12.5%) followed by lung (11.7%), liver (11.0%), heart (10.8%), and kidney (5.8%). Median time to CDI was 56 days (range 2-354) post-SOT. About 64% of patients had severe CDI. About 56.3% were treated with metronidazole, 13.8% with oral vancomycin, and 28.6% with both. About 28.6% of patients had recurrent CDI. In multivariable modeling, lung transplant recipient status was the only significant predictor of recurrent CDI (OR 4.97, 95% CI 2.11-11.78, P < .001) controlling for age, severe CDI, and pre-SOT CDI. Post-SOT CDI nearly doubled the risk of mortality at one year, in particular among those with severe CDI. CONCLUSIONS: In summary, CDI is highly prevalent, occurs early in the post-transplant period, usually severe, with a high rate of recurrence, and associated with increased mortality within 1 year after transplant. The early post-transplant period may be a crucial window to reduce CDI rates.

Use of the Electronic Health Record to Target Patients for Non-endoscopic Barrett's Esophagus Screening.

BACKGROUND: Clinical prediction models targeting patients for Barrett's esophagus (BE) screening include data obtained by interview, questionnaire, and body measurements. A tool based on electronic health records (EHR) data could reduce cost and enhance usability, particularly if combined with non-endoscopic BE screening methods. AIMS: To determine whether EHR-based data can identify BE patients. METHODS: We performed a retrospective review of patients ages 50-75 who underwent a first-time esophagogastroduodenoscopy. Data extracted from the EHR included demographics and BE risk factors. Endoscopy and pathology reports were reviewed for histologically confirmed BE. Screening criteria modified from clinical guidelines were assessed for association with BE. Subsequently, a score based on multivariate logistic regression was developed and assessed for its ability to identify BE subjects. RESULTS: A total of 2931 patients were assessed, and BE was found in 1.9%. Subjects who met screening criteria were more likely to have BE (3.3% vs. 1.1%, p = 0.001), and the criteria predicted BE with an AUROC of 0.65 (95% CI 0.59-0.71). A score based on logistic regression modeling included gastroesophageal reflux disease, sex, body mass index, and ever-smoker status and identified BE subjects with an AUROC of 0.71 (95% CI 0.64-0.77). Both prediction tools produced higher AUROCs in women than in men. CONCLUSIONS: EHR-based BE risk prediction tools identify BE patients with fair accuracy. While these tools may improve the efficiency of patient targeting for BE screening in the primary care setting, challenges remain to identify high-risk patients for non-invasive BE screening in clinical practice.

Functional Chest Pain and Esophageal Hypersensitivity: A Clinical Approach.

Functional chest pain, functional heartburn, and reflux hypersensitivity are 3 functional esophageal disorders defined by the Rome IV criteria. Specific criteria, combining symptoms and the results of objective testing, allow for an accurate diagnosis of these conditions. Management may include medications targeted at optimizing acid suppression or neuromodulation, as well as a host of complementary or alternative treatment options. Psychological and behavioral interventions, such as cognitive behavioral therapy and hypnotherapy, have displayed substantial benefits in the treatment of functional chest pain and functional heartburn. Acid suppression and focused neuromodulation are key evidence-based treatment options for reflux hypersensitivity.

Increased Risk of Pancreatitis after Endoscopic Retrograde Cholangiopancreatography Following a Positive Intraoperative Cholangiogram: A Single-Center Experience.

BACKGROUND/AIMS: To determine if patients with a positive intraoperative cholangiogram (IOC) who undergo a subsequent endoscopic retrograde cholangiopancreatography (ERCP) have an increased risk of post-ERCP pancreatitis (PEP) compared to those who undergo ERCP directly for suspected common bile duct stones. METHODS: A retrospective case-control study was performed from 2010 to 2016. Cases included inpatients with a positive IOC at cholecystectomy who underwent subsequent ERCP. The control group included age-sex matched cohorts who underwent ERCP for choledocholithiasis. Multivariate logistic regression was used to assess the association between PEP and positive IOC, adjusting for matching variables and additional potential confounders. RESULTS: Of the 116 patients that met the inclusion criteria, there were 91 women (78%) in each group. Nine patients (7.8%) developed PEP in the IOC group, compared to 3 patients in the control group (2.6%). The use of pancreatic duct stents and rectal indomethacin was similar in both groups. After adjusting for age, sex, total bilirubin levels, and any stent placement, patients with a positive IOC had a significantly increased risk of PEP (odds ratio, 4.79; 95% confidence interval, 1.05-21.89; p<0.05). CONCLUSION: In this single-center case-control study, there was a five-fold increased risk of PEP following a positive IOC compared to an age-sex matched cohort.

Cystic fibrosis is associated with an increased risk of Barrett's esophagus.

BACKGROUND: Cystic fibrosis (CF) patients have increased risks of gastrointestinal cancers, including esophageal adenocarcinoma. Gastroesophageal reflux disease (GERD) is highly prevalent in CF and manifests at early ages. CF patients may be at increased risk for long-term sequelae of chronic GERD, including Barrett's esophagus (BE). We aimed to assess whether patients with CF have an increased risk of BE or related neoplasia. METHODS: A matched cohort study was performed of adults with and without CF who had undergone upper endoscopy. Non-CF patients were matched in a 4:1 ratio by age, sex, year of exam, and endoscopist. Odds ratios were calculated for the association between CF and BE or related neoplasia, and multivariable logistic regression modeling was performed to adjust for matching variables and additional potential confounders. RESULTS: 122 CF patients underwent endoscopy, and 488 matched controls were identified. Seven (5.7%) CF patients had BE or related neoplasia, including one GE junction adenocarcinoma. Mean age of affected CF patients was 36.0, and 85.7% had a prior solid organ transplant. The odds of BE was significantly increased in CF patients (OR 2.91, 95% CI 1.08-7.81). The risk remained significantly increased in a multivariable model including matching variables (OR 3.32, 95% CI 1.19-9.22) and in a parsimonious model (OR 2.99, 95% CI 1.06-8.42). CONCLUSIONS: Adults with CF have a 3-fold increased risk of BE or related neoplasia and appears to develop at younger ages. Consideration should be given to screening for BE in select CF patients, especially those who have undergone solid organ transplantation.