Background & Aims It has been a challenge to confirm the association between laryngeal symptoms and physiologic reflux disease. We examined the ability of oropharyngeal pH tests (with the Restech Dx-pH system) and salivary pepsin tests (with Peptest) to discriminate between asymptomatic volunteers (controls) and subjects with a combination of laryngeal and reflux symptoms (laryngeal±reflux). Methods We performed a physician-blinded prospective cohort study of 59 subjects at a single academic institution. Adult volunteers were recruited and separated into 3 groups based on GerdQ and reflux symptom index scores: controls (n=20), laryngeal symptoms (n=20), or laryngeal+reflux symptoms (n=19). Subjects underwent laryngoscopy and oropharyngeal pH tests and submitted saliva samples for analysis of pepsin concentration. Primary outcomes included abnormal acid exposure and composite (RYAN) score for oropharyngeal pH tests and abnormal mean salivary pepsin concentration based on normative data. Results Complete oropharyngeal pH data were available from 53 subjects and complete salivary pepsin data from 35 subjects. We did not observe any significant differences between groups in percent time spent below pH 4.0, 5.0, 5.5, 6.0 or RYAN scores; or percent of subjects with positive results from tests for salivary pepsin (53% vs 40% vs 75%; P=.50, respectively). The laryngeal+reflux group had a significantly higher estimated mean concentration of salivary pepsin (117.9±147.4ng/mL) than the control group (32.4±41.9ng/mL) or laryngeal symptom group (7.5±11.2ng/mL) (P=.01 and P=.04, respectively). Conclusions Using current normative thresholds, oropharyngeal pH testing and salivary pepsin analysis are not able to distinguish between healthy volunteers and subjects with a combination of laryngeal and reflux symptoms.

BACKGROUND & AIMS:Although dysphagia is common, there is limited information about the prevalence and burden of illness of dysphagia in the United States. We performed a population-based survey of more than 31,000 adults to evaluate the epidemiology, clinical characteristics, and health careseeking behavior of individuals with dysphagia. METHODS:We performed a cross-sectional analysis of adults in the United States who completed an online, self-administered health survey from April 4 through April 19, 2018. All respondents were asked which of the following symptoms they had ever experienced (presented in random order): dysphagia, abdominal pain, bloating, bowel incontinence, constipation, diarrhea, heartburn/reflux, nausea/vomiting, or none of the above. Only respondents who selected dysphagia continued the remaining survey, which included questions about dysphagia severity, use of compensatory maneuvers, health care seeking, and esophageal comorbidities. We used multivariable regression methods to adjust for confounding. RESULTS:Of 31,129 individuals who participated in the survey, 4998 respondents (16.1%) reported experiencing dysphagia; 92.3% of these had symptoms in the previous week. We found that 16.3% of respondents described their dysphagia over the previous 7 days as either quite a bit or very severe. Drinking liquids to help with dysphagia (86.0%) and taking longer to finish eating (76.5%) were the most common compensatory maneuvers. Overall, 51.1% of individuals sought care for their difficulty swallowing; older age, male sex, having a usual source of care and insurance, having comorbidities, and more severe dysphagia symptoms increased the odds for seeking care (P < .05). The most commonly reported esophageal comorbidities were gastroesophageal reflux disease (30.9%), eosinophilic esophagitis (8.0%), and esophageal stricture (4.5%). CONCLUSIONS:In a large population-based survey, we found that dysphagia is common; 1 of 6 adults reported experiencing difficulty swallowing. However, half of individuals have not discussed their symptoms with a clinician and many could have treatable disorders.

In Saccharomyces cerevisiae, the sequence-specific binding of the negative regulator Rap1p provides a mechanism to measure telomere length: as the telomere length increases, the binding of additional Rap1p inhibits telomerase activity in cis. We provide evidence that the association of Rap1p with telomeric DNA in vivo occurs in part by sequence-independent mechanisms. Specific mutations in EST2 (est2-LT) reduce the association of Rap1p with telomeric DNA in vivo. As a result, telomeres are abnormally long yet bind an amount of Rap1p equivalent to that observed at wild-type telomeres. This behavior contrasts with that of a second mutation in EST2 (est2-up34) that increases bound Rap1p as expected for a strain with long telomeres. Telomere sequences are subtly altered in est2-LT strains, but similar changes in est2-up34 telomeres suggest that sequence abnormalities are a consequence, not a cause, of overelongation. Indeed, est2-LT telomeres bind Rap1p indistinguishably from the wild type in vitro. Taken together, these results suggest that Est2p can directly or indirectly influence the binding of Rap1p to telomeric DNA, implicating telomerase in roles both upstream and downstream of Rap1p in telomere length homeostasis.Telomeres are nucleoprotein structures that protect chromosome ends from nucleolytic digestion and preclude the recognition of normal ends as double-strand breaks (6). In most eukaryotes, telomeres are maintained by telomerase, a ribonucleoprotein that uses a short region of its RNA subunit as a template for reverse transcription. In Saccharomyces cerevisiae, a reverse transcriptase (RT) (EST2) and RNA subunit (TLC1) form the catalytic core of telomerase (18,21,35). Est2p contains at least three functional domains: an N-terminal TEN domain that anchors Est2p on its DNA substrate (23,24) and that may interact with other protein components (10), an RNA binding (RBD) region associates with that TLC1 RNA and contributes to dimerization (20), and an RT domain conserved among other telomerases and viral RTs (21).While many organisms synthesize perfect TG-rich telomeric repeats, several protozoa, fungi, slime molds, and plants have heterogeneous telomere sequences (40). S. cerevisiae displays considerable degeneracy, with a consensus of 5Ј-[(TG) 0-6 TG GGTGTG(G)] n (9). Several models have been proposed to explain this heterogeneity. An analysis of wild-type (WT) telomeres and telomeres generated in the presence of template mutations suggests that the registration of the telomere terminus occurs preferentially at the 3Ј end of the template, with processive synthesis through a central core region and decreasing processivity at the 5Ј end of the template (9, 33). In contrast, telomere junction fragments generated during chromosome healing events are more consistent with nonprocessive synthesis and patterning driven by substrate/template alignment (32). In humanized yeast cells, in which the yeast RNA template is replaced with that of humans, Est2p generates perfect hexanucleotide repeats, suggesting that the...

Introduction Predicting response to proton-pump inhibitor (PPI) therapy in patients with laryngeal symptoms is challenging. The Restech Dx-pH probe is a transnasal catheter that measures oropharyngeal pH. In this study, we aimed to investigate the prognostic potential of oropharyngeal pH monitoring to predict responsiveness to PPI therapy in patients with laryngeal symptoms. Methods We conducted a physician blinded prospective cohort study at a single academic institution between 1/2013–10/2014. Adult patients with Reflux Symptom Index scores (RSI) ≥13 off PPI therapy were recruited. Patients underwent video laryngoscopy and 24-hour oropharyngeal pH monitoring, followed by an 8–12 week trial of omeprazole 40 mg daily. Prior to, and following PPI therapy, patients completed various symptom questionnaires. The primary outcome was the association between PPI response and oropharyngeal pH metrics. PPI response was separated into three subgroups based on post-treatment RSI score and % RSI response: Non-response = RSI ≥ 13; Partial response = post-treatment RSI < 13 and change in RSI < 50%; and Complete response = post-treatment RSI < 13 and change in RSI ≥ 50%. The primary analysis utilized a multinomial logistic regression controlling for pre-treatment RSI score. A secondary analysis assessed the relationship between change in RSI (post-pre) and oropharyngeal pH metrics via ordinary least square regression. Results Thirty-four patients completed the study and were included in final analysis. Symptom response to PPI therapy was as follows: 50% no response, 15% partial-response and 35% complete-response. Non-responders had a higher pre-treatment RSI (P < 0.01). There were no significant differences in oropharyngeal acid exposure (below pH of 4.0, 5.0, 5.5, 6.0 and RYAN scores) between responder types. The secondary analysis noted a trend between lower PPI response and greater total percent time below pH of 5.0 (P = 0.03), upright percent time below pH of 5.0 (p = .07) and RYAN supine (corrected) (P = 0.03), as well as an association between PPI response and greater decreases in the Anxiety Sensitivity Inventory (P < 0.01), Brief Symptom Inventory-18 (P < 0.01), and Negative Affect Scale (P < 0.01). Discussion Oropharyngeal pH testing did not predict laryngeal symptom response to PPI therapy. Contrary to hypothesis, our study signaled that the degree of oropharyngeal acid exposure is inversely related to PPI response. In addition, reduction in negative affect and psychological distress parallels PPI response.

Reflux-associated laryngeal symptoms (RALS) is the process in which chronic laryngeal symptoms are related to gastroesophagopharyngeal reflux. Impairment of upper esophageal sphincter (UES) reflexes may predispose to esophagopharyngeal reflux. The novel noninvasive nonpharmacologic UES assist device (UESAD) applies external cricoid pressure to augment intraluminal UES pressure by 20 to 30 mm Hg and reduce esophagopharyngeal reflux events. This study aimed to assess the therapeutic efficacy of the UESAD in a pragmatic clinical setting, and to identify factors associated with symptom response among patients with suspected RALS.

Small intestinal bacterial overgrowth (SIBO) manifests with a variety of gastrointestinal symptoms, including bloating, flatulence, abdominal pain, nausea, dyspepsia, fatigue, diarrhea, and constipation [1]. SIBO has been implicated as a cause of hepatic encephalopathy and of d-lactic acidosis in patients with short bowel syndrome [2,3]. Moreover, SIBO is associated with a variety of conditions outside of the gastrointestinal system, including rosacea [4], restless legs syndrome [5], interstitial cystitis [6], and chronic prostatitis [7], and correlates with the level of somatic pain in fibromyalgia [8]. Along these lines, recent studies have reported a link between SIBO and cardiovascular disease.Ponziani et al. [9] recently published data linking SIBO with subclinical atherosclerosis through the vitamin K-dependent activity of the matrix GIa-protein (MGP), which maintains arterial structure and function through prevention of calcification of vessel walls and the regulation of the extracellular matrix. MGP is carboxylated by the cofactor vitamin K2 to assume its active form. Increased expression of the inactive, uncarboxylated MGP is a marker of low vitamin K2 status, associated with signs of early vascular disease such as arterial stiffness and vascular calcifications, as well as cardiovascular morbidity and mortality. The bulk of vitamin K2 in humans is derived from gut bacterial biosynthesis, and prior studies showed low circulating levels of vitamin K2 in patients with SIBO [10].In their prospective cohort study, 39 patients were included with SIBO suspected on the basis of gastrointestinal symptoms who also had low cardiovascular disease risk and no prior history of cardiovascular events. All patients underwent a glucose breath test, and 12 (39.0%) were diagnosed with SIBO. The median level of inactive MGP was significantly increased among patients with SIBO compared to patients without SIBO (9.5 vs 4.2 µg/L, p = 0.02). Correspondingly, arterial pulse wave velocity, which increases when there is an increase in arterial stiffness, was increased among patients with SIBO compared to that observed in the group without SIBO (10.25 vs 7.68 m/s, p = 0.002). The authors concluded, then, that SIBO is associated with reduced MGP activation as well as arterial stiffening, regarded as important indicators of subclinical atherosclerosis [9].In the current issue of Digestive Diseases and Sciences, Fialho et al. [11] expand upon this work by demonstrating a previously undescribed association between SIBO and coronary artery disease (CAD). In their study, they retrospectively reviewed medical records at a single tertiary care center in order to identify all patients who underwent a glucose hydrogen/methane breath test. Records were crossreferenced to identify 160 patients who had undergone left heart catheterization with coronary angiography at the same center. These records were reviewed to determine the presence and extent of CAD. Importantly, widely recognized risk factors for CAD such as age, smoking, diabetes, hypert...

No abstract

No abstract