Diagnostic thresholds and optimal collection protocol of salivary pepsin for gastroesophageal reflux disease.

Gastroesophageal reflux disease (GERD) is primarily diagnosed based on symptoms and response to a proton-pump inhibitor (PPI) trial. Gold standard testing requires an invasive endoscopic procedure, often with ambulatory pH monitoring. Salivary pepsin is a potential noninvasive modality for GERD diagnosis. This study aimed to assess diagnostic performance of salivary pepsin thresholds for GERD and determine optimal collection protocol of saliva in an external validation cohort. Over 10 months, adults with symptoms of GERD undergoing esophagogastroduodenoscopy with wireless pH-monitoring off PPI were enrolled. Saliva was self-collected by participants over 4 days across three different time points: fasting ante meridiem (AM), post-prandial, and bedtime (PM). Pepsin levels were calculated via Peptest. Pepsin variability and agreement were determined using linear mixed effects models and intraclass correlation. Validation of diagnostic threshold and performance characteristics were evaluated by receiver-operator curve analysis. Twenty participants enrolled in the study; 50% with physiologic acid exposure (acid exposure time < 4% no GERD) and 50% with elevated acid exposure (GERD). Mean pepsin concentrations were significantly lower in the AM (22.6 ± 25.2 ng/mL) compared to post-prandial (44.5 ± 36.7 ng/mL) and PM (55.4 ± 47.0 ng/mL). Agreement between pepsin concentrations across 3 days was substantial for AM samples (kappa 0.61), with lower agreement for post-prandial and PM samples. A single AM pepsin concentration of 25 ng/mL was 67% accurate for GERD with 56% sensitivity and 78% specificity. This validation study highlights fair accuracy and performance characteristics of a single fasting AM salivary pepsin concentration for the diagnosis of GERD.

Factors that Impact Day-to-Day Esophageal Acid Reflux Variability and Its Diagnostic Significance for Gastroesophageal Reflux Disease.

Gastroesophageal reflux disease (GERD) is a common disease affecting a significant number of adults both globally and in the USA. GERD is clinically diagnosed based on patient-reported symptoms, and the gold standard for diagnosis is ambulatory reflux monitoring, a tool particularly utilized in the common scenario of non-response to therapy or atypical features. Over the past 20 years, there has been a shift toward extending the duration of reflux monitoring, initially from 24 to 48 h and more recently to 96 h, primarily based on a demonstrated increase in diagnostic yield. Further, multiple studies demonstrate clinically relevant variability in day-to-day acid exposure levels in nearly 30% of ambulatory reflux monitoring studies. For these reasons, an ongoing clinical dilemma relates to the optimal activities patients should engage in during prolonged reflux monitoring. Thus, the aims of this review are to detail what is known about variability in daily acid exposure, discuss factors that are known to influence this day-to-day variability (i.e., sleep patterns, dietary/eating habits, stress, exercise, and medications), and finally provide suggestions for patient education and general GERD management to reduce variation in esophageal acid exposure levels.

Inherited thrombophilia and portal vein thrombosis in cirrhosis: A systematic review and meta-analysis.

BACKGROUND: Portal vein thrombosis (PVT) is common in cirrhosis. PVT is associated with high morbidity and mortality. Individual reports suggest that PVT occurs more frequently in patients with cirrhosis and inherited thrombophilia. The relationship between cirrhosis, PVT development, and inherited thrombophilia was explored in this study. The aim of the study was to determine whether cirrhotic patients with nontumoral PVT have an increased rate of inherited thrombophilia. METHODS: Studies were identified by searching electronic databases up to October 2017 with English language and human subject restrictions. Two independent reviewers screened citations and extracted data. Magnitude of effect was calculated to obtain aggregate estimates of effect size and 95% confidence intervals (CIs). Between-study variability and heterogeneity were assessed. RESULTS: Of 2893 citations identified, 9 studies composed of 1929 subjects with cirrhosis were included. The overall prevalence of PVT was 6.5% (n = 125). Both prothrombin G20210A mutation (odds ratio [OR], 2.43; 95% CI, 1.07-5.53; P = 0.03) and factor V Leiden (FVL) (OR, 1.98; 95% CI, 1.06-3.68; P = 0.03) were significantly associated with PVT risk. Methyltetrahydrofolate reductase C677T mutation was not associated with increased PVT risk. No heterogeneity or publication bias was observed. One important study with opposite findings could not be included due to lack of primary data. CONCLUSIONS: FVL and PTG20210A mutation were associated with increased PVT risk in patients with cirrhosis. This finding reframes the role of inherited thrombophilia in PVT development in patients with cirrhosis. Future prospective studies investigating screening for inherited thrombophilia in all cirrhosis patients with PVT seem warranted.