Effects of capsaicin on esophageal peristalsis in humans using high resolution manometry.

BACKGROUND: Capsaicin-containing red pepper sauce suspension augments esophageal contraction amplitude on conventional manometry. This study used high-resolution manometry (HRM) to investigate if capsaicin infusion modulates segmental esophageal smooth muscle peristalsis in healthy adults. METHODS: Sixteen healthy volunteers (mean age 37 years, 14 male) underwent HRM for the evaluation of primary peristalsis and secondary peristalsis using slow and rapid air distensions. Both primary and secondary peristalsis were assessed following infusions of capsaicin-containing red pepper sauce and saline. KEY RESULTS: Capsaicin infusion significantly increased heartburn symptoms compared to saline infusion (p < 0.001), and significantly decreased threshold volumes of secondary peristalsis during rapid air distensions (p = 0.02). The frequency of secondary peristalsis during rapid air distensions was significantly increased by capsaicin infusion (p = 0.03). Neither capsaicin infusion (p = 0.06) nor saline infusion (p = 0.27) altered threshold volume during slow air distensions. Capsaicin infusion significantly increased distal contractile integral (DCI) of primary peristalsis (p = 0.04), particularly in the proximal smooth muscle segment (p = 0.048). It enhanced secondary peristalsis during rapid air distensions (p = 0.003) but not during slow air distension (p = 0.23). Saline infusion significantly increased DCI of secondary peristalsis during rapid air distension (p = 0.01). CONCLUSIONS AND INFERENCES: Augmentation of distension-induced secondary peristalsis can be modulated by activation of capsaicin-sensitive afferents similar to mechanosensitive afferents. Capsaicin-induced augmentation of primary peristalsis isolates to the cholinergic-mediated proximal smooth muscle segment, which warrants study in ineffective esophageal motility to determine therapeutic potential.

Influence of Menthol Infusion on Esophageal Peristalsis in Patients With Ineffective Esophageal Motility.

Background/Aims: Activation of the cold receptor, transient receptor potential melastatin 8 (TRPM8) by menthol inhibits esophageal secondary peristalsis in healthy adults. Ineffective esophageal motility (IEM) is common. This study is to evaluate the effects of acute infusion of menthol on esophageal peristalsis in patients with IEM. Methods: Twenty patients with IEM (males 11, mean age 36) were studied for esophageal peristalsis using high-resolution manometry. All participant had primary peristalsis performed with 10 water swallows and secondary peristalsis generated with 10 rapid air injections of 20 mL via mid-esophageal infusion port. Two different sessions by randomly performing acute administration of placebo or menthol (3 mM) were used for testing their effects on esophageal peristalsis. Results: Menthol infusion had no effects on distal contractile integral (P = 0.471), distal latency (P = 0.58), or complete peristalsis (P = 0.251). Menthol infusion did not change basal lower esophageal sphincter pressure (P = 0.321), esophagogastric junction contractile integral (P = 0.758), or integrated relaxation pressure (P = 0.375) of primary peristalsis, but reduced upper esophageal sphincter pressure (P = 0.037). Infusion of menthol significantly reduced the frequency of secondary peristalsis for air injects of 20 mL (P = 0.002), but did not affect distal contractile integral of secondary peristalsis for air injections of 20 mL. Conclusion: This work has suggested that activation of TRPM8 by menthol can attenuate mechanosensitivity of secondary peristalsis in response to rapid air distension regardless of the presence of IEM.

Efficacy of jing Si herbal tea in functional dyspepsia: A double-blind, randomized, placebo-controlled study.

BACKGROUND: Functional dyspepsia (FD) is prevalent worldwide and is associated with gastrointestinal inflammation, mucosal anomalies, and shifts in microbiota metabolites like short chain fatty acids. This study assesses the efficacy of Jing Si herbal tea (JSHT) in alleviating FD symptoms, psychological distress, and influencing metabolites. METHODS: Adults with FD based on Rome IV criteria were included. Participants underwent physical and psychological evaluations, pre-treatment blood sampling, and were randomly assigned to JSHT or placebo groups for four weeks. Post-treatment, evaluations and Liquid Chromatography-Mass Spectrometry for gut metabolites were done. Successful response was defined by a 50% symptom reduction. Symptom intensity, sleep, depression, anxiety, and stress were measured using questionnaires. RESULTS: 26 patients (median age 55.5 years, range 22-77 years, 60.6% female) were studied. Both JSHT and placebo groups were similar at baseline. JSHT showed a higher response rate (69.2%) than placebo (23.1%, P = 0.018). JSHT recipients experienced notable reduction in upper gastrointestinal symptoms and anxiety (P = 0.005; P = 0.037). Increased serum butyrate was observed in improved patients (P = 0.01), whereas no major changes were detected in the placebo group. CONCLUSION: Four weeks of JSHT treatment ameliorated FD symptoms and anxiety, potentially linked to increased serum butyrate. This study suggests that JSHT has potential therapeutic role in patients with FD.

The Lyon Score: A Novel Reflux Scoring System Based on the Lyon Consensus 2.0 That Associates With Treatment Outcome From Antireflux Therapy.

INTRODUCTION: We explored if a score derived from parameters from esophageal testing could increase confidence in diagnosing conclusive gastroesophageal reflux disease and in predicting outcome. METHODS: A prediction score was developed using metrics based on Lyon Consensus 2.0 thresholds extracted from endoscopy and pH-impedance monitoring. The Lyon score was the sum of weighted scores derived from a logistic regression model. The outcome was response to antireflux therapy, defined as 50% reduction in global symptoms on validated questionnaires. An existing database of endoscopy-negative patients with typical reflux symptoms undergoing esophageal testing from 2 centers (Europe and the United States) constituted the developmental cohort, while 2 separate cohorts (Europe and Asia) served as validation cohorts. Receiver operating characteristics analysis determined performance of the Lyon score in predicting treatment response. RESULTS: In 281 developmental cohort patients (median age 53 years, 57.7% female), the Lyon score demonstrated an area under the curve (AUC) of 0.819 in predicting 50% symptom improvement ( P < 0.001) on receiver operating characteristics, with an optimal threshold of 6.25 (sensitivity 81.2%, specificity 73.4%). Of the individual components, only acid exposure time (AUC 0.799, P < 0.001), mean nocturnal baseline impedance (AUC 0.785, P < 0.001), and reflux episodes (AUC 0.764, P < 0.001) approached the Lyon score performance. The Lyon score segregated treatment response in both the European (AUC 0.908, P < 0.001) and Asian validation cohorts (AUC 0.637, P < 0.001) and outperformed the DeMeester score in sensitivity for predicting outcome in the developmental and Asian validation cohorts. DISCUSSION: The novel Lyon score segregates reflux phenotypes and identifies likelihood of symptom response from antireflux therapy.

Relevance of ineffective esophageal motility to striated esophageal muscle contraction: Studies with high-resolution manometry.

Striated esophageal muscle contraction (SEC) is important for pharyngeal swallowing and deglutition augmentation against aspiration. Its clinical relevance is unclear in patients with ineffective esophageal motility (IEM). In this study, we aimed to characterize and compare SEC in consecutive patients with and without IEM. All eligible patients were evaluated for SEC, primary and secondary peristalsis using high-resolution manometry (HRM) with one mid-esophageal injection port. Primary peristalsis was assessed with 10 5-mL liquid swallows and multiple rapid swallows (MRS), while secondary peristalsis was performed with rapid air injections of 20 mL. All peristatic parameters of HRM were measured, and SEC and its contractile integral (SECI) were evaluated. One hundred and forty patients (59.3% women, mean age 46.1 ± 13.1 years) were included. There was no difference in SECI between patients with and without IEM (p = 0.91). SECI was also similar between patients with and without secondary peristalsis for IEM (p = 0.63) or normal motility (p = 0.80). No difference in SECI was seen between patients with and without MRS for IEM (p = 0.55) or normal motility (p = 0.88). SECI was significantly higher in male patients than female patients in IEM patients (p = 0.01). SECI significantly correlated with age in patients with normal motility (r = -0.31, p = 0.01). Aging may have a negative impact on SEC in patients with normal motility, while gender difference in SECI occurs in IEM patients. Neither secondary peristalsis nor MRS influences SECI.

Impact of Esophageal Motility on Microbiome Alterations in Symptomatic Gastroesophageal Reflux Disease Patients With Negative Endoscopy: Exploring the Role of Ineffective Esophageal Motility and Contraction Reserve.

Background/Aims: Ineffective esophageal motility (IEM) is common in patients with gastroesophageal reflux disease (GERD) and can be associated with poor esophageal contraction reserve on multiple rapid swallows. Alterations in the esophageal microbiome have been reported in GERD, but the relationship to presence or absence of contraction reserve in IEM patients has not been evaluated. We aim to investigate whether contraction reserve influences esophageal microbiome alterations in patients with GERD and IEM. Methods: We prospectively enrolled GERD patients with normal endoscopy and evaluated esophageal motility and contraction reserve with multiple rapid swallows during high-resolution manometry. The esophageal mucosa was biopsied for DNA extraction and 16S ribosomal RNA gene V3-V4 (Illumina)/full-length (Pacbio) amplicon sequencing analysis. Results: Among the 56 recruited patients, 20 had normal motility (NM), 19 had IEM with contraction reserve (IEM-R), and 17 had IEM without contraction reserve (IEM-NR). Esophageal microbiome analysis showed a significant decrease in microbial richness in patients with IEM-NR when compared to NM. The beta diversity revealed different microbiome profiles between patients with NM or IEM-R and IEM-NR (P = 0.037). Several esophageal bacterial taxa were characteristic in patients with IEM-NR, including reduced Prevotella spp. and Veillonella dispar, and enriched Fusobacterium nucleatum. In a microbiome-based random forest model for predicting IEM-NR, an area under the receiver operating characteristic curve of 0.81 was yielded. Conclusions: In symptomatic GERD patients with normal endoscopic findings, the esophageal microbiome differs based on contraction reserve among IEM. Absent contraction reserve appears to alter the physiology and microbiota of the esophagus.

Esophageal motor abnormalities in gastroesophageal reflux disorders.

Gastroesophageal reflux disease (GERD), a prevalent condition with multifactorial pathogenesis, involves esophageal motor dysmotility as a key contributing factor to its development. When suspected GERD patients have an inadequate response to proton-pump inhibitor (PPI) therapy and normal upper endoscopy results, high-resolution manometry (HRM) is utilized to rule out alternative diagnosis such as achalasia spectrum disorders, rumination, or supragastric belching. At present, HRM continues to provide supportive evidence for diagnosing GERD and determining the appropriate treatment. This review focuses on the existing understanding of the connection between esophageal motor findings and the pathogenesis of GERD, along with the significance of esophageal HRM in managing GERD patients. The International GERD Consensus Working Group introduced a three-step method, assessing the esophagogastric junction (EGJ), esophageal body motility, and contraction reserve with multiple rapid swallow (MRS) maneuvers. Crucial HRM abnormalities in GERD include frequent transient lower esophageal sphincter relaxations, disrupted EGJ, and esophageal body hypomotility. Emerging HRM metrics like EGJ-contractile integral and innovative provocative maneuver like straight leg raise have the potential to enhance our understanding of factors contributing to GERD, thereby increasing the value of HRM performed in patients who experience symptoms suspected of GERD.

Validated Clinical Score to Predict Gastroesophageal Reflux in Patients With Chronic Laryngeal Symptoms: COuGH RefluX.

BACKGROUND & AIMS: Discerning whether laryngeal symptoms result from gastroesophageal reflux is clinically challenging and a reliable tool to stratify patients is needed. We aimed to develop and validate a model to predict the likelihood of gastroesophageal reflux disease (GERD) among patients with chronic laryngeal symptoms. METHODS: This multicenter international study collected data from adults with chronic laryngeal symptoms who underwent objective testing (upper gastrointestinal endoscopy and/or ambulatory reflux monitoring) between March 2018 and May 2023. The training phase identified a model with optimal receiver operating characteristic curves, and ß coefficients informed a weighted model. The validation phase assessed performance characteristics of the weighted model. RESULTS: A total of 856 adults, 304 in the training cohort and 552 in the validation cohort, were included. In the training phase, the optimal predictive model (area under the curve, 0.68; 95% CI, 0.62-0.74), was the Cough, Overweight/obesity, Globus, Hiatal Hernia, Regurgitation, and male seX (COuGH RefluX) score, with a lower threshold of 2.5 and an upper threshold of 5.0 to predict proven GERD. In the validation phase, the COuGH RefluX score had an area under the curve of 0.67 (95% CI, 0.62-0.71), with 79% sensitivity and 81% specificity for proven GERD. CONCLUSIONS: The externally validated COuGH RefluX score is a clinically practical model to predict the likelihood of proven GERD. The score classifies most patients with chronic laryngeal symptoms as low/high likelihood of proven GERD, with only 38% remaining as indeterminate. Thus, the COuGH RefluX score can guide diagnostic strategies and reduce inappropriate proton pump inhibitor use or testing for patients referred for evaluation of chronic laryngeal symptoms.

Effects of Codeine on Esophageal Peristalsis in Patients With Ineffective Esophageal Motility: Studies Using High-resolution Manometry.

Background/Aims: This study aims to evaluate the effects of acute codeine administration on primary and secondary esophageal peristalsis in patients with ineffective esophageal motility (IEM). Methods: Eighteen IEM patients (8 women; mean age 37.8 years, range 23-64 years) were enrolled in the study. The patients underwent high-resolution manometry exams, consisting of 10 single wet swallows, multiple rapid swallows, and ten 20 mL rapid air injections to trigger secondary peristalsis. All participants completed 2 separate sessions, including acute administration of codeine (60 mg) and placebo, in a randomized order. Results: Codeine significantly increased the distal contractile integral (566 ± 81 mmHg∙s∙cm vs 247 ± 36 mmHg∙s∙cm, P = 0.001) and shortened distal latency (5.7 ± 0.2 seconds vs 6.5 ± 0.1 seconds, P < 0.001) for primary peristalsis compared with these parameters after placebo treatment. The mean total break length decreased significantly after codeine treatment compared with the length after placebo (P = 0.003). Codeine significantly increased esophagogastric junction-contractile integral (P = 0.028) but did not change the 4-second integrated relaxation pressure (P = 0.794). Codeine significantly decreased the frequency of weak (P = 0.039) and failed contractions (P = 0.009), resulting in increased frequency of normal primary peristalsis (P < 0.136). No significant differences in the ratio of impaired multiple rapid swallows inhibition and parameters of secondary peristalsis were detected. Conclusions: In IEM patients, acute administration of codeine increases contraction vigor and reduces distal latency of primary esophageal peristalsis, but has no effect on secondary peristalsis. Future studies are required to further elucidate clinical relevance of these findings, especially in the setting of gastroesophageal reflux disease with IEM.

Diagnostic Yield of Ambulatory Reflux Monitoring Systems for Evaluation of Chronic Laryngeal Symptoms.

INTRODUCTION: Among patients with chronic laryngeal symptoms, ambulatory reflux monitoring off acid suppression is recommended to evaluate for laryngopharyngeal reflux (LPR). However, reflux monitoring systems are diverse in configuration and monitoring capabilities, which present a challenge in creating a diagnostic reference standard in these patients. This study aimed to compare diagnostic yield and performance between reflux monitoring systems in patients with chronic laryngeal symptoms. METHODS: This multicenter, international study of adult patients referred for evaluation of LPR over a 5-year period (March 2018-May 2023) assessed and compared diagnostic yield of pathologic gastroesophageal reflux (GER+) on ambulatory reflux monitoring off acid suppression. RESULTS: Of 813 patients, 296 (36%) underwent prolonged wireless pH, 532 (65%) underwent 24-hour pH-impedance monitoring, and 15 (2%) underwent both tests. Overall diagnostic yield for GER+ was 36% and greater for prolonged wireless pH compared with that for 24-hour pH-impedance monitoring (50% vs 27%; P < 0.01). Among 15 patients who underwent both prolonged wireless pH and 24-h pH-impedance monitoring, concordance between systems for GER+ was 40%. The most common source of discordance was strong evidence of GER+ across multiple days on prolonged wireless pH compared with no evidence of GER+ on pH-impedance. DISCUSSION: In this multicenter international study of patients with chronic laryngeal symptoms referred for LPR evaluation, diagnostic yield of ambulatory reflux monitoring off acid suppression was 36% and rose to 50% when using wireless pH monitoring. In patients referred for chronic laryngeal symptoms, 24-hour pH-impedance monitoring may risk a low negative predictive value in patients with unproven GER+ disease.

Esophageal secondary peristalsis following acid infusion and chemical clearance correlate with mucosal integrity and acid sensitivity in GERD patients.

Background: Acid sensitivity can be altered in patients with gastroesophageal reflux disease (GERD). Secondary peristalsis helps clear gastro-esophageal refluxate and residual ingested food bolus. Objectives: The aim of this study was to investigate the associations among acid sensitivity, esophageal mucosal integrity, chemical clearance, and secondary peristalsis before and after esophageal acid infusion. Design: This was an investigator-initiated, prospective, cross-sectional study. Methods: Adult reflux patients underwent high resolution manometry and 24 h impedance-pH monitoring off acid suppression to identify GERD phenotypes, including non-erosive reflux disease (NERD), reflux hypersensitivity (RH), and functional heartburn (FH). Secondary peristalsis was assessed using five rapid 20 mL air injections into the esophagus before and after infusion of hydrochloric acid (0.1 N) into the mid-esophagus. Conventional acid infusion parameters recorded included lag time, intensity rating, and sensitivity score. Chemical clearance was evaluated using the post-reflux swallow-induced peristaltic wave (PSPW), and mucosal integrity was assessed by the mean nocturnal baseline impedance (MNBI) derived from impedance-pH monitoring. Results: A total of 88 patients (age 21-64 years, 62.5% women) completed the study including 12 patients with NERD, 45 with RH, and 31 with FH. There was no significant difference in acid infusion parameters between patients with NERD, RH, and FH. Upon acid infusion, patients who exhibited successful secondary peristalsis had longer lag time, higher MNBI, and shorter bolus contact time than those without secondary peristalsis. Meanwhile, patients with intact PSPW demonstrated significantly higher intensity ratings in response to acid perfusion and higher MNBI than those with impaired PSPW. The lag time correlated positively with MNBI (r = 0.285; p = 0.007). Conclusion: In conclusion, the protective effect of esophageal secondary peristalsis and chemical clearance on esophageal mucosal integrity was demonstrated. Concerning acid sensitivity, longer lag time in patients with intact secondary peristalsis may be attributed to better esophageal mucosal integrity, while stronger intensity ratings may have a greater tendency to induce PSPW and protect esophageal mucosal integrity.

Application of Artificial Intelligence in Measuring Novel pH-Impedance Metrics for Optimal Diagnosis of GERD.

Novel metrics extracted from pH-impedance monitoring can augment the diagnosis of gastroesophageal reflux disease (GERD). Artificial intelligence (AI) is being widely used to improve the diagnostic capabilities of various diseases. In this review, we update the current literature regarding applications of artificial intelligence in measuring novel pH-impedance metrics. AI demonstrates high performance in the measurement of impedance metrics, including numbers of reflux episodes and post-reflux swallow-induced peristaltic wave index and, furthermore, extracts baseline impedance from the entire pH-impedance study. AI is expected to play a reliable role in facilitating measuring novel impedance metrics in patients with GERD in the near future.

Esophageal Hypervigilance and Visceral Anxiety Contribute to Symptom Severity of Laryngopharyngeal Reflux.

INTRODUCTION: Laryngopharyngeal reflux (LPR) is a clinical conundrum without a diagnostic gold standard. The Esophageal Hypervigilance and Anxiety Scale (EHAS) is a questionnaire designed for cognitive-affective evaluation of visceral sensitivity. We hypothesized that esophageal hypervigilance and symptom-specific anxiety have an etiopathological role in generation of LPR symptoms, especially when gastroesophageal reflux disease (GERD) cannot explain these symptoms. METHODS: Consecutive patients with LPR and/or GERD symptoms lasting >3 months were prospectively enrolled and characterized using the Reflux Symptom Index, GERD questionnaire, and EHAS. Eligible patients with negative endoscopy underwent 24-hour impedance-pH monitoring off acid suppression for phenotyping GERD and assessment of reflux burden, using conventional metrics (acid exposure time and number of reflux episodes) and novel metrics (mean nocturnal baseline impedance and postreflux swallow-induced peristaltic wave index). RESULTS: Of 269 enrolled patients (mean age 47.1 years, 21-65 years, 60.6% female), 90 patients were with concomitant GERD and LPR symptoms, 32 patients were with dominant LPR symptoms, 102 patients were with dominant GERD symptoms, and 45 were controls. Patients with concomitant GERD and LPR symptoms had higher EHAS than those with dominant GERD symptoms and controls ( P ≤ 0.001); patients with dominant LPR symptoms had higher EHAS than controls ( P = 0.007). On Pearson correlation, EHAS positively correlated with the Reflux Symptom Index. DISCUSSION: Esophageal hypervigilance and symptom-specific anxiety may be more important than reflux burden in LPR symptom perception.

Real-World Evidence of Effectiveness and Safety of Vedolizumab for Inflammatory Bowel Disease in Taiwan: A Prospective Nationwide Registry (VIOLET) Study.

BACKGROUND: This nationwide prospective registry study investigated the real-world effectiveness, safety, and persistence of vedolizumab (VDZ) in inflammatory bowel disease (IBD) patients in Taiwan. Disease relapse rates after VDZ discontinuation due to reimbursement restriction were assessed. METHODS: Data were collected prospectively (January 2018 to May 2020) from the Taiwan Society of IBD registry. RESULTS: Overall, 274 patients (147 ulcerative colitis [UC] patients, 127 Crohn's disease [CD] patients) were included. Among them, 70.7% with UC and 50.4% with CD were biologic-naïve. At 1 year, 76.0%, 58.0%, 35.0%, and 62.2% of UC patients and 57.1%, 71.4%, 33.3%, and 30.0% of CD patients achieved clinical response, clinical remission, steroid-free remission, and mucosal healing, respectively. All patients underwent hepatitis B and tuberculosis screening before initiating biologics, and prophylaxis was recommended when necessary. One hepatitis B carrier, without antiviral prophylaxis due to economic barriers, had hepatitis B reactivation during steroid tapering and increasing azathioprine dosage, which was controlled with an antiviral agent. No tuberculosis reactivation was noted. At 12 months, non-reimbursement-related treatment persistence rates were 94.0% and 82.5% in UC and CD patients, respectively. Moreover, 75.3% of IBD patients discontinued VDZ due to mandatory drug holiday. Relapse rates after VDZ discontinuation at 6 and 12 months were 36.7% and 64.3% in CD patients and 42.9% and 52.4% in UC patients, respectively. CONCLUSIONS: The findings demonstrated VDZ effectiveness in IBD patients in Taiwan, with high treatment persistence rates and favorable safety profiles. A substantial IBD relapse rate was observed in patients who had mandatory drug holiday.

Artificial intelligence facilitates measuring reflux episodes and postreflux swallow-induced peristaltic wave index from impedance-pH studies in patients with reflux disease.

BACKGROUND/AIM: Reflux episodes and postreflux swallow-induced peristaltic wave (PSPW) index are useful impedance parameters that can augment the diagnosis of gastroesophageal reflux disease (GERD). However, manual analysis of pH-impedance tracings is time consuming, resulting in limited use of these novel impedance metrics. This study aims to evaluate whether a supervised learning artificial intelligence (AI) model is useful to identify reflux episodes and PSPW index. METHODS: Consecutive patients underwent 24-h impedance-pH monitoring were enrolled for analysis. Multiple AI and machine learning with a deep residual net model for image recognition were explored based on manual interpretation of reflux episodes and PSPW according to criteria from the Wingate Consensus. Intraclass correlation coefficients (ICCs) were used to measure the strength of inter-rater agreement of data between manual and AI interpretations. RESULTS: We analyzed 106 eligible patients with 7939 impedance events, of whom 38 patients with pathological acid exposure time (AET) and 68 patients with physiological AET. On the manual interpretation, patients with pathological AET had more reflux episodes and lower PSPW index than those with physiological AET. Overall accuracy of AI identification for reflux episodes and PSPW achieved 87% and 82%, respectively. Inter-rater agreements between AI and manual interpretations achieved excellent for individual numbers of reflux episodes and PSPW index (ICC = 0.965 and ICC = 0.921). CONCLUSIONS: AI has the potential to accurately and efficiently measure impedance metrics including reflux episodes and PSPW index. AI can be a reliable adjunct for measuring novel impedance metrics for GERD in the near future.

Effects of the GABA(B) agonist baclofen on volitional swallowing in normal subjects.

The GABA(B) receptor agonist baclofen is known to suppress the rate of spontaneous swallowing but not pharyngeal muscle contraction. The extent to which baclofen may alter volitional swallowing is not currently known. We investigated the effects of baclofen in healthy subjects, hypothesizing that baclofen exposure would alter volume-regulation and/or piecemeal deglutition behaviors during volitional swallowing attempts. Pharyngeal high-resolution manometry impedance (P-HRM-I) protocol was used to assess swallowing function of 22 healthy adult volunteers (median 29 years) who were investigated on two occasions, receiving 40 mg baclofen (oral) 1 h before study, or placebo (randomized). Standard swallow function variables recommended by the pharyngeal HRM Working Group were derived for 5 ml, 10 ml, and 20 ml volumes of thin and extremely thick liquid challenges. Multiple swallow behaviors, comprising two swallows <5 s apart, were characterized. The spontaneous swallow rate was also determined. Baclofen exposure had no overall significant effect on swallow variables. Upper esophageal sphincter pressure was weaker during exposure to baclofen, during both the pre-deglutitive and post-deglutitive phases of the swallow (p < 0.05 during thick liquid swallows). Piecemeal swallows, where the bolus is separated in two potions, were significantly more common during 20 ml boluses (p = 0.002). Baclofen decreased the frequency of piecemeal deglutition overall. Baclofen has limited to no effect on volitional swallowing measures, however, does reduce the likelihood of initiation of piecemeal deglutition to large volume challenges.

Current advances in the diagnosis and management of gastroesophageal reflux disease.

Gastroesophageal reflux disease (GERD) is very common and defined as troublesome symptoms owing to excessive acid reflux. The spectrum of GERD is broad, including not only erosive esophagitis and Barrett's esophagus but also nonerosive reflux disease (NERD), reflux hypersensitivity, and functional heartburn. Patients with reflux symptoms despite normal endoscopy remain common clinical presentation, can be heterogeneous overlapping with functional gastrointestinal disorders. Ambulatory esophageal pH monitoring with and without impedance helps the diagnosis of NERD. Metrics such as baseline impedance and postreflux swallow induced peristaltic wave enhance diagnostic accuracy in patients with inconclusive diagnoses. The major treatment of all manifestations of GERD is acid suppression with proton pump inhibitors, while other therapies, such as reflux-reducing agents and adjunctive medications, can be individualized where the response to traditional management is incomplete. GERD patients often need long-term treatment due to frequent relapses. Anti-reflux surgery can be effective too. Endoscopic therapies have some promising results, but long-term outcomes remain to be determined.

Transient Hiatal Separation During Straight Leg Raise Can Predict Reflux Burden in Gastroesophageal Reflux Disease Patients With Ineffective Esophageal Motility.

Background/Aims: Straight leg raise (SLR) can be utilized to evaluate the integrity of the esophagogastric junction during high-resolution manometry (HRM). We aim to assess the value of transient hiatal separation during SLR in symptomatic reflux patients. Methods: Consecutive reflux patients undergoing esophageal HRM and pH monitoring were included. Transient hiatal separation was defined by a ≥ 1 cm separation between the lower esophageal sphincter and crural diaphragm during SLR. We compared esophageal motor patterns and reflux monitoring parameters between patients with normal, transiently abnormal and consistently abnormal esophagogastric junction morphology during SLR. Results: Of 85 (56.3% female, mean age: 46.7 ± 12.3 years) completed SLR, esophagogastric junction morphology was normal in 31 (36.5%), transient hiatal separation in 19 (22.3%), and consistently hiatal hernia in 35 (41.2%). The values of total acid exposure time (P = 0.016), longest acid reflux episodes (P = 0.024), and DeMeester scores (P = 0.016) were higher in hiatal hernia compared to patients with non-transient hiatal separation, but there were no differences between those with and without transient hiatal separation. Within ineffective esophageal motility, the presence of transient hiatal separation during SLR significantly associated with a higher total acid exposure time (P = 0.014), higher DeMeester scores (P = 0.019), higher total acid reflux events (P = 0.037), and higher longest acid reflux episodes (P = 0.006). Conclusion: Our work suggests that SLR may have value as a provocative test during HRM, and future outcome studies are warranted to elucidate the clinical relevance of motor abnormalities depicted from SLR.

Modifications decrease hepatic steatosis in Taiwanese with metabolic-associated fatty liver disease.

Metabolic-associated fatty liver disease (MAFLD) is a growing global problem associated with increasing obesity prevalence. Lifestyle modifications are currently recommended, including weight reduction, exercise, and diet control. This study evaluated the short-term effect of lifestyle modifications on transient elastography (TE) values in an obese population with MAFLD. Thirty-two MAFLD patients were recruited for this prospective study and all subjects participated in a 3-month program of lifestyle modification. Sequential demographic parameters and biochemical tests were compared before and after program completion. Liver fat and fibrosis changes were measured using TE with controlled attenuated parameter (CAP) and liver stiffness measurements (LSM). The mean age was 38.7 years old (10 males). The body weight (88.09 kg vs. 80.35 kg), body mass index (32.24 kg/m2 vs. 29.4 kg/m2 ), waist (103.19 cm vs. 95.75 cm), and hip circumference (111.67 cm vs. 104.75 cm), and blood pressure (128/78 mmHg vs. 119/71 mmHg) significantly improved before and after the intervention, respectively. Aspartate aminotransaminase (24.06 U/L vs. 18.91 U/L), alanine aminotransaminase (33 U/L vs. 23.72 U/L), creatinine (0.75 mg/dl vs. 0.70 mg/dl), cholesterol (176.41 mg/dl vs. 166.22 m/dl), gamma-glutamyl transferase (26.59 IU/L vs. 19.81 IU/L), and low-density lipoprotein cholesterol (115.63 mg/dl vs. 103.19 mg/dl) also improved after the 3-month intervention. The average CAP significantly decreased after intervention (297.5 dB/m vs. 255.0 dB/m), however, no significant difference in LSM was observed (5.24 kPa vs. 4.82 kPa). The current study suggests that short-term lifestyle modification can effectively improve hepatic steatosis, and TE may serve as a monitoring tool for therapeutic intervention.

Improvement of patient-reported outcomes in patients achieving sustained virologic response with direct-acting antivirals for hepatitis C virus infection.

BACKGROUND: Patient-reported outcome (PRO) in patients with chronic hepatitis C virus (HCV) infection (CHC) after successful direct-acting antiviral (DAA) therapy remains elusive. The study aimed to investigate the impact of DAA therapy on health-related quality of life (HRQoL). We also assess the associated factors predictive of HRQoL change after sustained virologic response (SVR) to HCV therapy. METHODS: CHC patients receiving DAA therapy were prospectively recruited. They completed paired HRQoL assessments which included Short-Form-36 (SF-36), Pittsburgh Sleep Quality Index (PSQI) score, Taiwanese Depression Questionnaire score, and State Trait Anxiety Inventory (STAI) score before treatment and at Week 12 off-treatment. Clinical data and characteristics were compared in a paired manner. RESULTS: A total of 158 patients achieved SVR (SVR rate: 96.6%) were enrolled into the final analysis. Improvement of depression, anxiety, digestive symptoms, and SF-36 items of vitality, body pain, physical functioning, emotional functioning, social functioning, and mental health were demonstrated among SVR patients. Sleep quality, or other SF-36 items were not significantly changed after the treatment. Multivariate analysis revealed that improvement of sleep quality, depression, and anxiety were associated with better HRQoL. CONCLUSION: SVR to HCV therapy by DAA significantly improved PROs including HRQoL.