The integrated relaxation pressure may not be an appropriate gold standard for deglutitive relaxation due to reliance on a single intragastric reference sensor.

BACKGROUND: Integrated relaxation pressure (IRP) calculation depends on the selection of a single gastric reference sensor. Variable gastric pressure readings due to sensor selection can lead to diagnostic uncertainty. This study aimed to examine the effect of gastric reference sensor selection on IRP measurement and diagnosis. METHODS: We identified high-resolution manometry (HRM) conducted between January and November 2017 with at least six intragastric reference sensors. IRP measurements and Chicago Classification 3.0 (CCv3) diagnoses were obtained for each of six gastric reference sensors. Studies were categorized as "stable" (no change in diagnosis) or "variable" (change in diagnosis with gastric reference selection). Variable diagnoses were further divided into "variable normal/dysmotility" (≥1 normal IRP measurement and ≥1 CCv3 diagnosis), or "variable dysmotility" (≥1 CCv3 diagnosis, only elevated IRP measurements). Bland-Altman plots were used to compare IRP measurements within HRM studies. KEY RESULTS: The analysis included 100 HRM studies, among which 18% had variable normal/dysmotility, and 10% had variable dysmotility. The average IRP difference between reference sensors was 6.7 mmHg for variable normal/dysmotility and 5.9 mmHg for variable dysmotility. The average difference between the proximal-most and distal-most sensors was -1.52 mmHg (lower limit of agreement -10.03 mmHg, upper limit of agreement 7.00 mmHg). CONCLUSIONS & INFERENCES: IRP values can vary greatly depending on the reference sensor used, leading to inconsistent diagnoses in 28% of HRM studies. Choosing the correct gastric reference sensor is crucial for accurate test results and avoiding misdiagnosis. Standardization of reference sensor selection or supportive testing for uncertain results should be considered.

Esophageal Hypocontractile Disorders and Hiatal Hernia Size Are Predictors for Long Segment Barrett's Esophagus.

Background/Aims: Presently, there is paucity of information about clinical predictors, especially esophageal motor abnormalities, for long segment Barrett's esophagus (LSBE) as compared with short segment Barrett's esophagus (SSBE). The aims of this study are to compare the frequency of esophageal function abnormalities between patients with LSBE and those with SSBE and to determine their clinical predictors. Methods: This was a multicenter cohort study that included all patients with a diagnosis of BE who underwent high-resolution esophageal manometry. Motility disorders were categorized as hypercontractile disorders or hypocontractile disorders and their frequency was compared between patients with LSBE and those with SSBE. Multivariable logistic regression modeling was used to calculate the odds of being diagnosed with LSBE relative to SSBE for demographics, comorbidities, medication use, endoscopic findings, and the type of motility disorders. Results: A total of 148 patients with BE were identified, of which 89 (60.1%) had SSBE and 59 (39.9%) LSBE. Patients with LSBE had a significantly larger hiatal hernia and higher likelihood of erosive esophagitis than patients with SSBE (P = 0.002). Patients with LSBE had a significantly lower mean LES resting pressure, distal contractile integral, distal latency, and significantly higher failed swallows and hypocontractile motility disorders than those with SSBE (P < 0.05). Hiatal hernia and hypocontractile motility disorder increased the odds of LSBE by 38.0% and 242.0%, as opposed to SSBE. Conclusions: The presence of a hypocontractile motility disorder increased the risk for LSBE. Furthermore, the risk for LSBE was directly associated with the length of the hiatal hernia.

The Effect of Bariatric Surgery and Endoscopic Procedures on Gastroesophageal Reflux Disease.

Obesity is a global epidemic posing a significant burden on patients and healthcare systems. Gastroesophageal reflux disease is associated with obesity and its prevalence is also growing worldwide. Numerous bariatric surgeries and endoscopic procedures have arisen to assist with weight loss and management of obesity-related conditions. However, the effect of these interventions on reflux is variable and the evidence is often conflicting. To date, Roux-en-Y gastric bypass remains the gold-standard for attaining both reflux and weight loss management, however novel endoscopic techniques are quickly becoming more prevalent as an alternative to surgery. This review aims to summarize currently available endoscopic and surgical weight loss procedures and their impact on reflux symptoms while emphasizing areas requiring additional investigation.

Demographics Predict Stage III/IV Colorectal Cancer in Individuals Under Age 50.

GOALS: The goal of this study was to quantify the association between demographic factors and advanced colorectal cancer (CRC) in patients under age 50. BACKGROUND: CRC incidence in the United States has declined in older individuals but increased in those under age 50 (early-onset). More than 60% of early-onset CRC patients present with advanced disease (stage III/IV), but predictors of stage in this population are poorly defined. STUDY: We analyzed CRC cases diagnosed between age 20 and 49 in the United States Surveillance, Epidemiology, and End Results (SEER) 18 database during 2004 to 2015. Logistic regression models were fit to assess the impact of age, sex, race, ethnicity, marital status, and cancer site on the probability of advanced disease. RESULTS: The analysis included 37,044 cases. On multivariable regression, age was inversely associated with advanced disease. Relative to 45 to 49-year-olds, 40 to 44-year-olds had 8% greater odds of having advanced CRC, and 20 to 24-year-olds had 53% greater odds. Asians, blacks, and Pacific Islanders had 10%, 12%, and 45% greater odds of advanced disease compared with whites. Compared with nonpartnered individuals, those with partners had 11% lower odds of advanced CRC. Both right-sided and left-sided colon cancer were more likely to be diagnosed at stage IV compared with rectal cancer. CONCLUSIONS: Among individuals with early-onset CRC, younger age, Asian, black, or Pacific Islander race, and being nonpartnered were predictors of advanced disease at presentation. Colon cancer was more likely to be diagnosed at stage IV than rectal cancer. Patient characteristics associated with advanced CRC may indicate both differences in tumor biology and disparities in health care access.

Overlap Between GERD and Functional Esophageal Disorders-a Pivotal Mechanism for Treatment Failure.

ᅟRefractory GERD is very common, and while many different underlying mechanisms have been identified, the main focus has remained on residual reflux (acidic or non-acidic). Recently, Rome IV introduced two new concepts with important impact on patients with refractory GERD. They include the introduction of the reflux hypersensitivity group and the proposal that GERD can overlap with a functional esophageal disorder. Recent studies have demonstrated that the latter affects approximately three quarters of the GERD patients who failed PPI once daily.

Clinically Divergent Mutation Effects on the Structure and Function of the Human Cardiac Tropomyosin Overlap.

The progression of genetically inherited cardiomyopathies from an altered protein structure to clinical presentation of disease is not well understood. One of the main roadblocks to mechanistic insight remains a lack of high-resolution structural information about multiprotein complexes within the cardiac sarcomere. One example is the tropomyosin (Tm) overlap region of the thin filament that is crucial for the function of the cardiac sarcomere. To address this central question, we devised coupled experimental and computational modalities to characterize the baseline function and structure of the Tm overlap, as well as the effects of mutations causing divergent patterns of ventricular remodeling on both structure and function. Because the Tm overlap contributes to the cooperativity of myofilament activation, we hypothesized that mutations that enhance the interactions between overlap proteins result in more cooperativity, and conversely, those that weaken interaction between these elements lower cooperativity. Our results suggest that the Tm overlap region is affected differentially by dilated cardiomyopathy-associated Tm D230N and hypertrophic cardiomyopathy-associated human cardiac troponin T (cTnT) R92L. The Tm D230N mutation compacts the Tm overlap region, increasing the cooperativity of the Tm filament, contributing to a dilated cardiomyopathy phenotype. The cTnT R92L mutation causes weakened interactions closer to the N-terminal end of the overlap, resulting in decreased cooperativity. These studies demonstrate that mutations with differential phenotypes exert opposite effects on the Tm-Tn overlap, and that these effects can be directly correlated to a molecular level understanding of the structure and dynamics of the component proteins.

Oesophageal sensation in response to high PCO(2) and acidic solutions in nonerosive reflux disease.

BACKGROUND: Heartburn is commonly associated with the presence of acid in the oesophageal lumen. However, in patients with nonerosive reflux disease (NERD), the mechanism by which acid traverses the mucosa is not clear. We hypothesized that the luminal acid signal traverses the oesophageal epithelium in the form of the highly permeant gas CO(2) , which then is reconverted to H(+) in the submucosa. MATERIALS AND METHODS: Ten patients with heartburn, normal upper endoscopy and increased oesophageal acid exposure (NERD patients) and 10 healthy subjects were enrolled. Perceptual responses to intraoesophageal acid (0·1 N HCl solution) and a high PCO(2) solution were determined using a randomized cross over design. Stimulus-response functions to perfusions were quantified by three parameters: lag time to symptom perception, intensity rating and perfusion sensitivity score. RESULTS: In NERD patients, the difference in lag time to typical symptom perception, intensity rating and perfusion sensitivity score between high PCO(2) and acid perfusions was statistically significant (P = 0·02, 0·01 and 0·02, respectively). However, the difference in the same perfusion parameters between acid and high PCO(2) perfusions was nonsignificant in healthy controls. When NERD and controls were compared, the difference between the different perfusion variables was nonsignificant (adjusted to age). CONCLUSIONS: In NERD subjects, acid perfusion reliably evoked heartburn symptoms of greater intensity than in healthy controls. Nevertheless, a high PCO(2) perfusion failed to produce symptoms in either group.