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Background: The usefulness of high-resolution impedance manometry (HRIM) in patients who underwent total gastrectomy with Roux-en-Y (R-Y) anastomosis has never been well validated. This study aimed to investigate whether intraesophageal pressure affects quality of life in patients who underwent total gastrectomy with R-Y anastomosis. Methods: The participants comprised 12 patients who underwent total gastrectomy for gastric cancer between October 2014 and July 2022 and underwent a postsurgical HRIM examination. The association between the HRIM data and Postgastrectomy Syndrome Assessment Scale-37 (PGSAS-37) questionnaires was analyzed. Results: Esophageal body motility was normal in almost all patients. The anastomosis shape (circular stapler and overlap method with linear stapler) did not influence intraesophageal pressure. The integrated relaxation pressure and lower esophageal sphincter (LES) residual pressure during swallowing-induced relaxation were involved in "diarrhea subscale" scores (p = 0.0244 and p = 0.0244, respectively). The average maximum intrabolus pressure was not involved in postgastrectomy symptom. The contractile front velocity correlated with the "indigestion subscale," "diarrhea subscale," and "constipation subscale" (p = 0.0408, p = 0.0143, and p = 0.0060, respectively). The distal latency, i.e., the time from upper esophageal sphincter relaxation to contractile deceleration, was also associated with the "abdominal pain subscale" (p = 0.0399). LES pressure and esophageal body motility affected patients' quality of life after total gastrectomy. Conclusions: HRIM for the evaluation of intraesophageal pressure is useful for the functional assessment of esophagojejunostomy with the R-Y reconstruction after total gastrectomy. [ABSTRACT FROM AUTHOR]

Gastroesophageal reflux disease (GERD), a prevalent clinical condition, is often attributed to aberrant esophageal motility, leading to gastric content reflux and associated symptoms or complications. The rising incidence of GERD presents an escalating healthcare challenge. Endoscopic and esophageal reflux monitoring can provide a basis for the diagnosis of patients with gastroesophageal reflux disease, but when the diagnostic basis is at an inconclusive value, some additional supportive evidence will be needed. Advanced technology is the key to improving patient diagnosis, accurate assessment, and the development of effective treatment strategies. High-resolution esophageal manometry (HREM) and endoscopic functional lumen imaging probe (EndoFLIP) represent the forefront of esophageal motility assessment. HREM, an evolution of traditional esophageal manometry, is considered the benchmark for identifying esophageal motility disorders. Its widespread application in esophageal dynamics research highlights its diagnostic significance. Concurrently, EndoFLIP's emerging clinical relevance is evident in diagnosing and guiding the treatment of coexisting esophageal motility issues. This review integrates contemporary research to delineate the contributions of HREM, EndoFLIP, and novel technologies in GERD. It examines their efficacy in facilitating an accurate diagnosis, differentiating similar gastrointestinal disorders, quantifying the extent of reflux, assessing the severity of the disease, forecasting patient responsiveness to proton pump inhibitor therapy, and guiding decisions for surgical interventions. The overarching aim is to deepen the understanding of GERD's underlying mechanisms and advance the formulation of holistic, efficacious treatment approaches. [ABSTRACT FROM AUTHOR]

Background/Aims: Cholecystokinin (CCK) administration has been shown to reduce lower esophageal sphincter (LES) pressure in normal subjects in manometric studies. Functional luminal imaging probe (FLIP) panometry offers a method to assess esophageal motility in response to sustained distension though mechanisms related to this response remain unexplored. The aim of this study is to evaluate the effect of CCK-8 on the esophageal response to distension in asymptomatic volunteers using FLIP. Methods: Esophageal response to distension was studied in 7 asymptomatic volunteers (mean age ± SD [27 ± 2]; 86% female) before and after CCK-8 administration in a crossover study design. During sedated endoscopy, FLIP was performed twice with CCK-8 administered via intravenous push in one of 2 protocols: during filling (n = 4) or during emptying (n = 3). Esophagogastric junction distensibility index (EGJ-DI) at 60 mL fill volume and esophageal body contractile response patterns were analyzed. Results: During the baseline FLIP study, all subjects had a contractile response with repetitive antegrade contractions both before and after CCK-8 administration. However, a sustained LES contraction or a sustained occluding contraction with esophageal shortening was observed in all subjects in the filling protocol, but in none during the emptying protocol. EGJ-DI was similar before and after CCK-8 during both filling (4.7 ± 1.9 mm2/mmHg vs 4.3 ± 1.8 mm2/mmHg) and emptying protocol (7.5 ± 1.4 mm2/mmHg vs 6.9 ± 0.6 mm2/mmHg). Conclusion: While EGJ-DI appeared unaffected by CCK-8 administration in asymptomatic volunteers, CCK induced spastic-reactive contractions of the LES during distention suggesting that exogenous CCK interferes with normal LES relaxation during secondary peristalsis. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background/Aims: There is an increased incidence of gastroesophageal reflux disease (GERD) after lung transplantation (LT) that can be associated with graft dysfunction. It is unclear if the underlying esophageal motility changes in GERD are different following LT. This study aimed to use esophageal high-resolution manometry (HRM) to explore GERD mechanisms in LT recipients compared to matched controls. Methods: This was a retrospective study including patients with pathologic acid reflux who underwent HRM and pH testing at our healthcare facility July 2012 to October 2019. The study included 12 LT recipients and 36 controls. Controls were matched in a 1:3 ratio for age, gender, and acid exposure time (AET) Results: LT recipients had less hypotensive esophagogastric junction (EGJ) (mean EGJ-contractile integral 89.2 mmHg/cm in LT vs 33.9 mmHg/cm in controls, P < 0.001). AET correlated with distal contractile integral and total EGJ-contractile integral only in LT group (r = -0.79, P = 0.002 and r = -0.57, P = 0.051, respectively). Conclusions: Following LT, acid reflux is characterized by a less hypotensive EGJ compared to controls with similar AET. The strongest correlation with AET after LT was found to be esophageal peristaltic vigor. These results add to the understanding of reflux after LT and may help tailor an individualized treatment plan. [ABSTRACT FROM AUTHOR]

Most species of the bone-devouring marine annelid, Osedax, display distinct sexual dimorphism with macroscopic sedentary females rooted in bones and free-living microscopic dwarf males. The paedomorphic male resembles the non-feeding metatrochophore larva in size, presence of eight pairs of chaetae, and a head ciliation potentially representing a residual prototroch. The male development may thus uniquely reiterate and validate the theoretical heterochrony process "progenesis", which suggests that an accelerated sexual maturation and early arrest of somatic growth can lead to a miniaturized and paedomorphic adult. In this study, we describe the postembryonic larval and juvenile organogenesis of Osedax japonicus to test for a potential synchronous arrest of somatic growth during male development. Five postembryonic stages could be distinguished, resembling day one to five in the larval development at 10°C: (0D) first cleavage of fertilized eggs (embryos undergo unequal spiral cleavage), (1D) pre-trochophore, with apical organ, (2D) early trochophore, + prototroch, brain, circumesophageal connectives and subesophageal commissure, (3D) trochophore, + telotroch, four ventral nerves, (4D) early metatrochophore, + protonephridia, dorsal and terminal sensory organs, (5D) metatrochophore, + two ventral paratrochs, mid-ventral nerve, posterior trunk commissure, two dorsal nerves; competent for metamorphosis. The larval development largely mirrors that of other lecithotrophic annelid larvae but does not show continuous chaetogenesis or full gut development. Additionally, O. japonicus larvae exhibit an unpaired, mid-dorsal, sensory organ. Female individuals shed their larval traits during metamorphosis and continue organogenesis (including circulatory system) and extensive growth for 2-3 weeks before developing oocytes. In contrast, males develop sperm within a day of metamorphosis and display a synchronous metamorphic arrest in neural and muscular development, retaining a large portion of larval features post metamorphosis. Our findings hereby substantiate male miniaturization in Osedax to be the outcome of an early and synchronous offset of somatic development, fitting the theoretical process "progenesis". This may be the first compelling morpho-developmental exemplification of a progenetic origin of a microscopic body plan. The presented morphological staging system will further serve as a framework for future examination of molecular patterns and pathways determining Osedax development. [ABSTRACT FROM AUTHOR]

BACKGROUND: The functional lumen imaging probe (FLIP) evaluates esophagogastric junction (EGJ) opening and esophageal contractility. Both post hoc and real-time analyses are possible, but reproducibility and reliability of analysis remain undefined. This study assesses inter- and intra-rater agreement of normative FLIP measurements among novice and experienced users. METHODS: Eight motility experts from different institutions independently evaluated de-identified video recordings from 27 asymptomatic healthy subjects using FLIP. Interpretation methods simulating a post-procedure and a live procedure setting were tested. Novice FLIP users (n = 3) received training prior to post-procedure interpretation. Experienced FLIP users (n = 5) interpreted using both methods. Users recorded maximum EGJ and distal esophageal body diameter, distensive pressure, and EGJ distensibility index (EGJ-DI), at balloon fill volumes of 50-, 60-, and 70 ml, as well as repetitive antegrade contractions (RACs). Inter- and intra-rater agreements of diameters, distensive pressure and EGJ-DI were assessed by intra-class correlation coefficient (ICC) and Pearsons correlation coefficient (PCC). Percentage agreement evaluated inter- and intra-rater reliability for RACs. KEY RESULTS: Novice and experienced users acquired normative FLIP metrics. Good-to-excellent inter- and intra-rater reliability were achieved for all variables at 60 ml balloon fill volumes. Median parameters at 60 ml balloon fill volume were as follows: EGJ-DI 5.5 mm2 /mmHg, maximum EGJ diameter 18.6 mm, distensive pressure at maximum EGJ diameter 48.1 mmHg, and distal esophageal body diameter 19.5 mm. CONCLUSIONS AND INFERENCES: Normative FLIP parameters can be reliably extracted from FLIP videos using both real-time and post hoc analyses, with high reliability between experienced and novice users.

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.

Background and aim: Laryngopharyngeal reflux disease (LPRD) is primarily characterized by discomfort in the pharynx and has limited treatment options. This research aimed to assess the efficacy of transcutaneous auricular vagus nerve stimulation (tVNS) in patients with LPRD and delve into the potential underlying mechanisms. Methods: A total of 44 participants, diagnosed with LPRD were divided into two groups randomly. Twice-daily stimulation was delivered for 2 weeks for patients in experimental group, with stimulation ranging from 1.0  mA to 1.5  mA (n  =  22), while the control group underwent sham tVNS (n  =  22) with the same stimulation parameters and different anatomical location. The severity of symptoms and levels of anxiety and depression were monitored using questionnaires. Highresolution esophageal manometry data were collected, and the patients’ autonomic function was assessed through heart rate variability analysis. Results: There was a positive correlation between reflux symptom index (RSI) scores and low frequency/high frequency (LF/HF) ratio (r  =  0.619; p  <  0.001), Hamilton anxiety scale (HAMA) scores (r  =  0.623; p  <  0.001), and Hamilton depression scale (HAMD) scores (r  =  0.593; p  <  0.001). Compared to the pretVNS phase, RSI (p  <  0.001), HAMA (p  <  0.001), and HAMD (p  <  0.001) scores were significantly reduced after 2 weeks of treatment. Additionally, the resting pressure of the upper esophageal sphincter (UESP; p  <  0.05) and lower esophageal sphincter (LESP; p  <  0.05) showed significant enhancement. Notably, tVNS led to an increase in root mean square of successive differences (RMSSD; p  <  0.05) and high frequency (HF; p  <  0.05) within heart rate variability compared to the pre-treatment baseline. Compared to the control group, RSI (p  <  0.001), HAMA (p  <  0.001), and HAMD (p  <  0.001) scores in tVNS group were significantly lower at the end of treatment. Similarly, the resting pressure of UESP (p  <  0.05) and LESP (p  <  0.05) in tVNS group were significantly higher than that of control group. Notably, RMSSD (p  <  0.05) and HF (p  <  0.05) in tVNS group were significantly higher than that of control group. Conclusion: This study demonstrated that tVNS as a therapeutic approach is effective in alleviating LPRD symptoms. Furthermore, it suggests that improvements in esophageal motility could be associated with vagus nervedependent mechanisms. [ABSTRACT FROM AUTHOR]

Abnormal cyclic motor pattern (CMP) activity is implicated in colonic dysfunction, but the only tool to evaluate CMP activity, high-resolution colonic manometry (HRCM), remains expensive and not widely accessible. This study aimed to validate body surface colonic mapping (BSCM) through direct correlation with HRCM. Synchronous meal-test recordings were performed in asymptomatic participants with intact colons. A signal processing method for BSCM was developed to detect CMPs. Quantitative temporal analysis was performed comparing the meal responses and motility indices (MI). Spatial heat maps were also compared. Post-study questionnaires evaluated participants' preference and comfort/distress experienced from either test. 11 participants were recruited and 7 had successful synchronous recordings (5 females/2 males; median age: 50 years [range 38–63]). The best-correlating MI temporal analyses achieved a high degree of agreement (median Pearson correlation coefficient (Rp) value: 0.69; range 0.47–0.77). HRCM and BSCM meal response start and end times (Rp = 0.998 and 0.83; both p < 0.05) and durations (Rp = 0.85; p = 0.03) were similar. Heat maps demonstrated good spatial agreement. BSCM is the first non-invasive method to be validated by demonstrating a direct spatio-temporal correlation to manometry in evaluating colonic motility. [ABSTRACT FROM AUTHOR]

Background and Aims: Ultrasonography has shown that eosinophils accumulate in each segment of the esophageal mucosa in human EoE, ultimately promoting esophageal motility dysfunction; however, no mechanistic evidence explains how or why this accumulation occurs. Methods: Quantitative PCR, ELISA, flow cytometry, immunostaining, and immunofluorescence analyses were performed using antibodies specific to the related antigens and receptors. Results: In deep esophageal biopsies of EoE patients, eosinophils and mast cells accumulate adjacent to nerve cell-derived VIP in each esophageal segment. qRT-PCR analysis revealed five- to sixfold increases in expression levels of VIP, CRTH2, and VAPC2 receptors and proteins in human blood- and tissue-accumulated eosinophils and mast cells. We also observed a significant correlation between mRNA CRTH2 levels and eosinophil- and nerve cell-derived VIPs in human EoE (p < 0.05). We provide evidence that eosinophil and mast cell deficiency following CRTH2 antagonist treatment improves motility dysfunction in a chronic DOX-inducible CC10-IL-13 murine model of experimental EoE. Conclusions: CRTH2 antagonist treatment is a novel therapeutic strategy for inflammatory cell-induced esophageal motility dysfunction in IL-13-induced chronic experimental EoE. [ABSTRACT FROM AUTHOR]

High-resolution manometry (HRM) facilitates the detailed evaluation of esophageal motility. In December 2020, Chicago classification (CC) version 4.0 introduced modifications to improve consistency and accuracy. We conducted this study to compare the differences in the interpretations of HRM examinations between CC 3.0 and 4.0. Consecutive HRM records at a Taiwan tertiary medical center, including wet swallows and MRS performed in both supine and sitting positions from October 2019 to May 2021, were retrospectively reviewed and analyzed using both CC versions 3.0 and 4.0. A total of 105 patients were enrolled, and 102 patients completed the exam, while three could not tolerate HRM sitting up. Refractory gastroesophageal reflux disease (GERD) symptoms (n = 65, 63.7%) and dysphagia (n = 37, 36.3%) were the main indications. A total of 18 patients (17.6%) were reclassified to new diagnoses using CC 4.0. Of the 11 patients initially diagnosed with absent contractility, 3 (27.3%) were reclassified as having Type 1 achalasia. Of the 18 patients initially diagnosed with IEM, 6 (33.3%) were reclassified as normal. The incidence of diagnosis changes was similar in both the dysphagia and refractory GERD symptoms groups (21.6% versus 15.3%, p = 0.43). The use of CC 4.0 led to changes in the diagnoses of esophageal motility disease, irrespective of examination indications. Early adoption improves the accuracy of diagnoses and affects patient management. [ABSTRACT FROM AUTHOR]

Background/Aims: While surgery remains a standard treatment for primary esophageal motility disorders (PEMDs), per-oral endoscopic myotomy (POEM) has recently evolved as an alternative. Systematic data on current trends of invasive procedures for PEMDs in Germany are missing. Methods: Hospital discharge data were used to evaluate trends and mortality of invasive treatment options for PEMDs in Germany between 2011 and 2019. Results: 4543 cases of PEMDs (achalasia: n = 4349, dyskinesia of the esophagus: n = 194) receiving open surgery (n = 200), minimal invasive surgery (n = 2366), or POEM (n = 1977) were identified. The relative proportion of POEM significantly increased from 10.9% (2011) to 65.7% (2019). Hospital mortality was 0.2%. The median duration of mechanical ventilation was significantly lower in POEM patients (29.4 hours) compared to open (274.0 hours) or minimal invasive (91.9 hours) surgery. The duration of hospitalization was lowest among POEM patients (5.7 days) compared to surgical procedures (13.7 and 7.7 days). Conclusion: While the low in-hospital mortality of all procedures combined confirms the solid safety profile of invasive procedures in general, our findings show that POEM has the lowest duration of mechanical ventilation and hospitalization compared to invasive surgical options. [ABSTRACT FROM AUTHOR]

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 highresolution 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. [ABSTRACT FROM AUTHOR]

Background/Aims It has been suggested that STW5 (Iberogast) reduces heartburn symptoms in patients with functional dyspepsia, but underlying mechanisms of action are unclear. The aim of this study is to investigate whether STW5 affects esophageal sensitivity or esophageal motility, thereby reducing occurrence and perception of reflux events. Methods We performed a double-blind, randomized, placebo-controlled, crossover trial in patients with functional dyspepsia (Rome IV) and reflux symptoms. After 4 weeks of treatment with either placebo or STW5, patients were studied with an esophageal acid perfusion test and ambulatory 24-hour pH-impedance monitoring. Results A total of 18 patients (7 men, median age 54, range [19-76]), were included in the study. Although we found no statistical difference in our primary outcome the total Reflux Disease Questionnaire score 2.33 (0.25-4.33) vs 2.67 (1.17-4.00), P = 0.347, "gastroesophageal reflux disease" and "regurgitation" subscale scores were lower after STW5 treatment compared to placebo (P = 0.049 and P = 0.007). There was no statistical difference in number of reflux events, acid exposure time and acid sensitivity scores between STW5 and placebo. In a subgroup analysis of patients with pH-metry confirmed gastroesophageal reflux disease, treatment with STW5 significantly reduced the total number of acidic reflux events (P = 0.028). Moreover, in patients with reflux esophagitis, the median lag time to acid perception increased after STW5 treatment (P = 0.042). Conclusions We found some indications pointing towards a beneficial effect of STW5 on reflux symptoms in dyspeptic patients, with reduction of esophageal hypersensitivity as a potential underlying mechanism. Our findings will have to be confirmed in larger studies. [ABSTRACT FROM AUTHOR]

Background/Aims Esophageal manometry is the gold standard for esophageal motility evaluation. High-resolution esophageal manometry with impedance (HRIM) allows concurrent assessment of bolus transit and manometry. Inconsistencies between concomitant impedance and manometry data pose a clinical dilemma and has not yet been addressed. We aim to assess interpretation trends of HRIM data among gastroenterologists worldwide. Methods A cross-sectional study using an anonymous survey was conducted among gastroenterologists worldwide. Statistical analysis was performed to compare responses between providers. Results We received responses from 107 gastroenterologists (26 countries). Most were adult providers (69, 64.5%), and most (77, 72.0%) had > 5 years of experience. Impedance was found to be helpful by 83 (77.6%) participants, but over 30% reported inconsistencies between impedance and manometry data. With incomplete bolus clearance and normal manometry 41 (38.7%) recommended observation, 41 (38.7%) recommended 24-hours pH-impedance, and 16 (15.1%) recommended prokinetics. With abnormal manometry and complete bolus clearance, 60 (57.1%) recommended observation while 18 (17.1%) recommended 24-hours pH impedance and 15 (14.3%) recommended prokinetics. A significant difference was found between providers from different continents in treating cases with discrepancy between impedance and manometry findings (P < 0.001). No significant differences were seen in responses between adult versus pediatric providers and between providers with different years of experience. Conclusions There is no consensus on interpreting HRIM data. Providers' approaches to studies with inconsistencies between manometry and impedance data vary. There is an unmet need for guidelines on interpreting impedance data in HRIM studies. [ABSTRACT FROM AUTHOR]

Peroral endoscopic myotomy (POEM), a novel minimally invasive treatment for esophageal achalasia, has been shown to be effective and safe for both adult and pediatric patients. However, studies on its application in children in Taiwan and its impact on growth and esophageal motility are lacking. We conducted a retrospective study on consecutive pediatric patients who were diagnosed with esophageal achalasia at National Taiwan University Hospital and underwent POEM during 2015–2022. Disease characteristics and treatment outcomes were analyzed. Ten patients (age 16.9 ± 3.1 years), nine newly diagnosed and one previously treated with pneumatic dilatation, underwent POEM for achalasia (type I/II/III: 3/7/0). Average symptom duration before diagnosis was 19.4 ± 19.9 months, mean POEM procedure time was 83.6 ± 30.7 min, and clinical success (Eckardt score ≤3) was achieved in all patients. Eight patients experienced mild adverse events during POEM, but none required further endoscopic or surgical intervention. Over a mean follow-up period of 3.7 ± 1.6 years, mean Eckardt score decreased significantly from 5.7 ± 2.4 to 1.1 ± 0.7 (p = 0.0001). The BMI z-score also increased significantly after POEM (p = 0.023). Five patients received follow-up high-resolution impedance manometry (HRIM), and all had improved lower esophageal sphincter resting pressures (p = 0.011), body contractility, and bolus transit (p = 0.019). POEM is an effective and safe treatment for pediatric achalasia in Taiwan. Early diagnosis and treatment with POEM may help to restore esophageal function and nutrition status in children. [ABSTRACT FROM AUTHOR]

Introduction: The relationship between the metabolically healthy obesity (MHO) phenotype and the occurrence of gastroesophageal reflux disease (GERD) and inefficient esophageal motility (IEM) is still unclear. Thus, we assessed the association between different metabolic obesity phenotypes and GERD and IEM using empirical data. Methods: We collected clinical and test data of 712 patients, including 24-h multichannel intraluminal impedance-pH (24-h MII-pH) monitoring, high-resolution manometry (HRM), and endoscopy. We divided 567 individuals into four categories according to their metabolic obesity phenotype: metabolically unhealthy non-obesity (MUNO), metabolically unhealthy obesity (MUO), metabolically healthy non-obesity (MHNO), and MHO. We compared differences in the 24-h MII-pH monitoring, HRM, and endoscopy findings among the four metabolic obesity phenotypes. Results: Patients with the MUNO, MHO, or MUO phenotype showed a greater risk of IEM and GERD (pathologic acid exposure time [AET] >6%) compared with patients with the MHNO phenotype. Regarding the HRM results, patients with the MHNO or MUNO phenotype had a lower integrated relaxation pressure, esophageal sphincter pressure, and esophagogastric junction contractile integral, and more ineffective swallows than patients with the MHO or MUO phenotype (p < 0.05). In terms of 24-h MII-pH, patients with the MHO or MUO phenotype had a higher total, upright, and supine AET; a higher total number of reflux episodes (TRs); and a lower mean nocturnal baseline impedance and post-reflux swallow-induced peristaltic wave index compared with those with the MHNO or MUNO phenotype (all p < 0.05). Considering the odds ratio of 19.086 (95% confidence interval 6.170–59.044) for pathologic AET and 3.659 (95% confidence interval 1.647–8.130) for IEM, patients with the MUO phenotype had the greatest risk after adjusting for all confounding variables. Conclusion: Obesity and metabolic disorders increase the risk of GERD and IEM. Obesity has a greater impact on esophageal dysmotility and pathologic acid exposure than metabolic diseases.

Gastroesophageal reflux disease (GERD), a prevalent clinical condition, is often attributed to aberrant esophageal motility, leading to gastric content reflux and associated symptoms or complications. The rising incidence of GERD presents an escalating healthcare challenge. Endoscopic and esophageal reflux monitoring can provide a basis for the diagnosis of patients with gastroesophageal reflux disease, but when the diagnostic basis is at an inconclusive value, some additional supportive evidence will be needed. Advanced technology is the key to improving patient diagnosis, accurate assessment, and the development of effective treatment strategies. High-resolution esophageal manometry (HREM) and endoscopic functional lumen imaging probe (EndoFLIP) represent the forefront of esophageal motility assessment. HREM, an evolution of traditional esophageal manometry, is considered the benchmark for identifying esophageal motility disorders. Its widespread application in esophageal dynamics research highlights its diagnostic significance. Concurrently, EndoFLIP’s emerging clinical relevance is evident in diagnosing and guiding the treatment of coexisting esophageal motility issues. This review integrates contemporary research to delineate the contributions of HREM, EndoFLIP, and novel technologies in GERD. It examines their efficacy in facilitating an accurate diagnosis, differentiating similar gastrointestinal disorders, quantifying the extent of reflux, assessing the severity of the disease, forecasting patient responsiveness to proton pump inhibitor therapy, and guiding decisions for surgical interventions. The overarching aim is to deepen the understanding of GERD’s underlying mechanisms and advance the formulation of holistic, efficacious treatment approaches.

Summary: Phase separation has emerged as a fundamental principle for organizing viral and cellular membraneless organelles. Although these subcellular compartments have been recognized for decades, their biogenesis and mechanisms of regulation are poorly understood.Here, we investigate the formation of membraneless inclusion bodies (IBs) induced during the infection of a plant rhabdovirus, tomato yellow mottle‐associated virus (TYMaV). We generated recombinant TYMaV encoding a fluorescently labeled IB constituent protein and employed live‐cell imaging to characterize the intracellular dynamics and maturation of viral IBs in infected Nicotiana benthamiana cells.We show that TYMaV IBs are phase‐separated biomolecular condensates and that viral nucleoprotein and phosphoprotein are minimally required for IB formation in vivo and in vitro. TYMaV IBs move along the microfilaments, likely through the anchoring of viral phosphoprotein to myosin XIs. Furthermore, pharmacological disruption of microfilaments or inhibition of myosin XI functions suppresses IB motility, resulting in arrested IB growth and inefficient virus replication.Our study establishes phase separation as a process driving the formation of liquid viral factories and emphasizes the role of the cytoskeletal system in regulating the dynamics of condensate maturation. [ABSTRACT FROM AUTHOR]

Background: The esophagogastric junction (EGJ) is classified into 3 anatomical subtypes according to lower esophageal sphincter-crural diaphragm (LES-CD) separation. We aimed to assess their relationship to esophageal motility, reflux characteristics, and symptom perception. Methods: We analyzed data from 1740 consecutive patients with typical reflux symptoms, who underwent high resolution manometry and a 24-h pH-impedance study during a 13-year period. A diagnosis of gastroesophageal reflux disease (GERD) was made if acid exposure time (AET) was >6%. EGJ types were classified as 1, 2, or 3, if LES-CD separation was up to 1 cm, 1-3 cm, or =3 cm, respectively. Results: EGJ type distribution was 72.2%, 22.1% and 5.7%, for types 1, 2 and 3, respectively. GERD was diagnosed in 31.2% and was more common among patients with EGJ type 2/3 vs. 1 (P<0.001). Length of LES-CD separation significantly correlated with AET and number of reflux episodes. Patients with type 2 or 3 EGJ more often showed ineffective or absent peristalsis compared with type 1 (P=0.008 and P<0.001 respectively). In the multivariate analysis, EGJ type 2/3 correlated with AET (P=0.001) and reflux episodes (P=0.041) but not with positive symptomatic markers or with ineffective/absent peristalsis. Conclusions: Our study confirms that EGJ anatomical morphology is a strong risk factor for GERD and correlates with both AET and the number of reflux events, though the length of separation is more important than the type. The multivariate analysis revealed that EGJ type 2 or 3 was not correlated with symptom perception or esophageal hypomotility. [ABSTRACT FROM AUTHOR]

Background: In high resolution manometry (HRM), distal contractile integral post multiple rapid swallow augmentation is considered as contraction reserve. The relationship between contraction reserve and esophageal acid reflux remains unclear. The aim of this study was to explore the correlation between contraction reserve and esophageal acid exposure in ineffective esophageal motility (IEM) and normal HRM. Methods: Patients who underwent HRM and ambulatory reflux monitoring were retrospectively screened. Those with diagnosis of normal HRM or IEM were included in the analysis. The proportion of patients with abnormal acid exposure time (AET) was compared between patients with and without contraction reserve. Multivariate regression analysis was performed to determine the predictors of abnormal AET and contraction reserve. Results: A total of 338 patients, including 264 normal HRM and 74 IEM, were included in the analysis. In patients with normal HRM, proportion of abnormal total AET (AET > 6.0%) was significantly lower in patients with supine contraction reserve than patients without contraction reserve (13.85% vs. 24.63%, p = 0.027). Multivariate regression analysis showed that supine contraction reserve could independently predict abnormal total AET (OR = 0.468, 95% CI: 0.249–0.948, p = 0.034), while upright contraction reserve trended strongly (OR = 0.558, 95% CI: 0.290–1.071, p = 0.079). Subgroup analysis showed that upright contraction reserve was an independent predictor of abnormal total AET in patients with 50–70% infective swallows (OR = 0.205, 95% CI: 0.051–0.821, p = 0.025), whereas supine contraction reserve did not have predictive value (p = 0.359). Conclusions: Supine contraction reserve correlates with esophageal acid reflux in patients with normal HRM, while only upright contraction reserve correlates with esophageal acid reflux in patients with infective swallows of 50–70%. [ABSTRACT FROM AUTHOR]

Background: Previous studies have shown that ALDH2 and ADH1B genes may be associated with alcohol metabolism and the risk of esophageal squamous cell carcinoma (ESCC), with inconsistent results. This meta‐analysis aimed at comprehensively assessing the associations between ALDH2 and ADH1B polymorphisms and the risk of ESCC to synthesize and clarify the evidence. Methods: We calculated summary estimates of the associations between four genetic variants (rs671 and rs674 in ALDH2, and rs1229984 and rs1042026 in ADH1B) and the ESCC risk across 23 publications in the additive model and allelic model. Venice criteria, Bayesian false discovery probability (BFDP), and false‐positive reporting probability (FPRP) were used to assess the strength of epidemiological evidence. Heterogeneity among studies was evaluated by using the Higgin's I2 statistic, and publication bias was assessed by using funnel plots and Begg's test. A Mendelian randomization (MR) analysis was performed to determine the causal association between alcohol intake and esophageal cancer risk. Data from the HaploReg v4.1 and PolyPhen‐2 were analyzed for functional annotations. Results: Of the four genetic variants, rs671 of ALDH2 was associated with a significantly reduced risk of ESCC (OR: 0.60, 95% CI: 0.50–0.73), whereas rs1229984 of ADH1B was associated with a significantly increased risk (2.50, 95% CI: 1.70–3.69) in the additive model. In the allelic model, the variant rs1229984 of ADH1B also increased the risk of ESCC (OR: 1.50; 95% CI: 1.21–1.87). The result for the variant rs671 was considered as strong epidemiological evidence. Functional annotations identified that the four variants were related to the enhancer histone marks and motif changes. The other two variants were not associated with the ESCC risk (rs674 of ALDH2 OR: 1.22, 95% CI: 0.71–2.12; rs1042026 of ADH1B OR: 1.28, 95% CI: 0.52–3.14) in the additive model. The MR analysis did not find a causal effect of alcohol on the esophageal cancer risk. Conclusions: The results showed that ADH1B rs1229984 was significantly associated with an increased the risk of ESCC. [ABSTRACT FROM AUTHOR]

The article discusses the need for an updated classification of esophageal motility disorders using high-resolution impedance manometry (HRIM). HRIM combines high-resolution manometry (HRM) and impedance to diagnose patients with dysphagia. The article highlights the limitations of HRM in providing information about bolus transit and the discrepancies that can arise between HRM metrics and impedance values. A survey study conducted among gastroenterologists worldwide revealed that there is no consensus on how to manage incomplete bolus clearance. The article suggests that future guidelines should address these discrepancies and provide criteria or alternatives for interpreting impedance values. [Extracted from the article]

Chicago Classification version 4.0 (CC v4.0), published in 2021, presents several modifications largely aimed at minimizing over-diagnosis of inconclusive patterns on high-resolution manometry (HRM). These include: 1) introduction of a standardized HRM protocol for consistency among centers, 2) emphasis on the need for supportive data in instances of inconclusive manometric patterns, 3) required presence of relevant symptoms in certain instances to reduce over-diagnosis and inappropriate interventions, and 4) classification as disorders of EGJ outflow or disorders of peristalsis. These updates aim to improve the clinical application of HRM and patient outcomes.

In up to half of patients with symptoms suspected to stem from gastroesophageal reflux disease (GERD), these symptoms persist despite treatment with daily proton pump inhibitor (PPI) therapy. The symptoms may be characterized as typical (eg, heartburn or regurgitation) or atypical (eg, chest pain or cough). These refractory symptoms, which are frequently encountered in clinical practice, may stem from GERD as well as non-GERD etiologies. Among those patients with objective GERD proven on esophagogastroduodenoscopy (EGD) and/ or ambulatory reflux testing, approximately one-fifth may manifest suboptimal symptom response to PPI therapy. After introducing the initial evaluation of patients with suspected GERD symptoms, this article discusses approaches to the esophageal diagnostic workup of patients with refractory symptoms in the setting of proven GERD, focusing on EGD, high-resolution manometry (HRM), and pH-impedance monitoring during treatment with PPI therapy. EGD evaluates for esophagitis, peptic stricture, and hiatal hernia, as well as eosinophilic esophagitis. HRM rules out confounding esophageal motor disorders, identifies behavioral disorders, characterizes the antireflux barrier, and assesses esophageal contractile reserve to help tailor potential antireflux interventions. pH-impedance monitoring during treatment with PPI therapy can help distinguish between PPI-refractory GERD-as evidenced by pathologic acid exposure despite PPI therapy and/or excess burden of reflux events regardless of acidity-and PPI-controlled GERD. This article also discusses potential approaches for patients with symptoms stemming from refractory GERD, encompassing lifestyle, pharmacologic, endoscopic, and surgical management options.

Abstract Background Esophageal motility disorders are a group of disorders associated with dysfunctional swallowing resulting from impaired neuromuscular coordination. Phosphodiesterase 5 (PDE-5) inhibitors induce smooth relaxation and are proposed as a treatment option for esophageal motility disorders such as achalasia. Methods This study is conducted based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). We systematically searched MEDLINE/ PubMed, Scopus, EMBASE, and Web of Science databases for esophageal outcomes of individuals treated with PDE5 inhibitors. A random effect meta-analysis was conducted. Results A total of 14 studies were included. They were conducted in different countries, with Korea and Italy having the highest number of articles. The main drug assessed was sildenafil. PDE-5 inhibitors resulted in a significant reduction in lower esophageal sphincter pressure (SMD − 1.69, 95% CI: -2.39 to -0.99) and the amplitude of contractions (SMD − 2.04, 95% CI: -2.97 to -1.11). Residual pressure was not significantly different between the placebo and sildenafil groups (SMD − 0.24, 95% CI: -1.20 to 0.72). Furthermore, a recent study reported contractile integral, stating that ingestion of sildenafil leads to a significant reduction in distal contractile integral and a significant increase in proximal contractile integral. Conclusion PDE-5 inhibitors significantly reduce LES resting pressure and esophageal peristaltic vigor, decreasing esophageal body contractility and contraction reserve. Therefore, using these drugs in patients affected by esophageal motility disorders may potentially improve their condition regarding symptom relief and prevention of further associated complications. Future reports investigating larger sample size is necessary in order to establish definite evidence regarding the efficacy of these drugs.

(1) Background: Dysphagia affects around 16% of the US population. Diagnostic tests like X-ray barium swallow and endoscopy are used initially to diagnose the cause of dysphagia, followed by high-resolution esophageal manometry (HRM). If the above tests are normal, the patient is classified as functional dysphagia (FD), suggesting esophageal sensory dysfunction. HRM records only the contraction phase of peristalsis, not the distension phase. We investigated the utilization of esophageal distension–contraction patterns for the automatic classification of FD, using artificial intelligent shallow learners. (2) Methods: Studies were performed in 30 healthy subjects and 30 patients with FD. Custom-built software (Dplots 1.0) was used to extract relevant esophageal distension–contraction features. Next, we used multiple shallow learners, namely support vector machines, random forest, K-nearest neighbors, and logistic regression, to determine which had the best performance in terms of accuracy, precision, and recall. (3) Results: In the proximal segment, LR produced the best results, with accuracy of 91.7% and precision of 92.86%, using only distension features. In the distal segment, random forest produced accuracy of 90.5% and precision of 91.1% using both pressure and distension features. (4) Conclusions: Findings emphasize the crucial role of abnormality in the distension phase of peristalsis in FD patients. [ABSTRACT FROM AUTHOR]

Background: Achalasia is a rare condition characterized by dysfunction of esophageal motility and impaired relaxation of the lower esophageal sphincter. Anesthetic management of these patients is challenging due to the elevated risk of regurgitation and aspiration. Case presentation: A 53-year-old man diagnosed with achalasia was scheduled for renal cancer surgery before esophageal myotomy. Since his severe dysphagia suggested the possibility of vomiting and aspiration under anesthesia, a stomach tube was inserted before induction of general anesthesia. After preoxygenation, rapid sequence induction was performed and an antiemetic was administered to prevent postoperative vomiting. Although anesthetic management was uneventful, the inserted stomach tube coiled up in the dilated esophagus and substantial residue was aspirated via the tube even after a prolonged fasting period. Conclusion: Anesthesiologists should be familiar with achalasia even though it is an uncommon disease, since affected patients are at risk of regurgitation and aspiration under anesthesia. [ABSTRACT FROM AUTHOR]

Modern omics technologies can generate massive amounts of biomedical data, providing unprecedented opportunities for individualized precision medicine. However, traditional statistical methods cannot effectively process and utilize such big data. To meet this new challenge, machine learning algorithms have been developed and applied rapidly in recent years, which are capable of reducing dimensionality, extracting features, organizing data and forming automatable data-driven clinical decision systems. Data-driven clinical decision-making have promising applications in precision medicine and has been studied in digestive diseases, including early diagnosis and screening, molecular typing, staging and stratification of digestive malignancies, as well as precise diagnosis of Crohn's disease, auxiliary diagnosis of imaging and endoscopy, differential diagnosis of cystic lesions, etiology discrimination of acute abdominal pain, stratification of upper gastrointestinal bleeding (UGIB), and real-time diagnosis of esophageal motility function, showing good application prospects. Herein, we reviewed the recent progress of data-driven clinical decision making in precision diagnosis of digestive diseases and discussed the limitations of data-driven decision making after a brief introduction of methods for data-driven decision making. [ABSTRACT FROM AUTHOR]

Achalasia is a rare motility disorder of the esophagus caused by the gradual degeneration of myenteric neurons. Immune-mediated ganglionitis has been proposed to underlie the loss of myenteric neurons. Here, we measure the immune cell transcriptional profile of paired lower esophageal sphincter (LES) tissue and blood samples in achalasia and controls using single-cell RNA sequencing (scRNA-seq). In achalasia, we identify a pattern of expanded immune cells and a specific transcriptional phenotype, especially in LES tissue. We show C1QC+ macrophages and tissue-resident memory T cells (TRM), especially ZNF683+ CD8+ TRM and XCL1+ CD4+ TRM, are significantly expanded and localized surrounding the myenteric plexus in the LES tissue of achalasia. C1QC+ macrophages are transcriptionally similar to microglia of the central nervous system and have a neurodegenerative dysfunctional phenotype in achalasia. TRM also expresses transcripts of dysregulated immune responses in achalasia. Moreover, inflammation increases with disease progression since immune cells are more activated in type I compared with type II achalasia. Thus, we profile the immune cell transcriptional landscape and identify C1QC+ macrophages and TRM as disease-associated immune cell subsets in achalasia. Achalasia is a rare motility disorder of the esophagus resulting from abnormal immune responses, but the immunologic mechanism is unclear. Here the authors use scRNA-seq of PBMC and esophageal lower sphincter tissue and find C1QC+ macrophages and tissue-resident memory T cells with expanded compositions and altered transcriptional profiles in achalasia. [ABSTRACT FROM AUTHOR]

Prevailing methods for esophageal motility assessments, such as perfusion manometry and probe-based function imaging, frequently overlook the intricate stress fields acting on the liquid-filled balloons at the forefront of the probing device within the esophageal lumen. To bridge this knowledge gap, we innovatively devised an infusible flexible balloon catheter, equipped with a quartet of PVDF piezoelectric sensors. This design, working in concert with a bespoke local key-node analytical algorithm and a sensor array state analysis model, seeks to shed new light on the dynamic mechanical characteristics at pivotal esophageal locales. To further this endeavor, we pioneered a singular closed balloon system and a complementary signal acquisition and processing system that employs a homogeneously distributed PVDF piezoelectric sensor array for the real-time monitoring of dynamic mechanical nuances in the esophageal segment. An advanced analytical model was established to scrutinize the coupled physical fields under varying degrees of balloon inflation, thereby facilitating a thorough dynamic stress examination of local esophageal nodes. Our rigorous execution of static, dynamic, and simulated swallowing experiments robustly substantiated the viability of our design, the logical coherence of our esophageal key-point stress analytical algorithm, and the potential clinical utility of a flexible esophageal key-node stress detection balloon probe outfitted with a PVDF array. This study offers a fresh lens through which esophageal motility testing can be viewed and improved upon. [ABSTRACT FROM AUTHOR]

Objective: The gastrointestinal tract is commonly involved in patients with systemic sclerosis (SSc) with varied manifestations. As our understanding of SSc gastrointestinal disease pathogenesis and risk stratification is limited, we sought to investigate whether patterns of esophageal dysfunction associate with specific clinical phenotypes in SSc. Methods: Patients enrolled in the Johns Hopkins Scleroderma Center Research Registry who completed high‐resolution esophageal manometry (HREM) studies as part of their clinical care between 2011 and 2020 were identified. Associations between esophageal abnormalities on HREM (absent contractility [AC], ineffective esophageal motility [IEM], hypotensive lower esophageal sphincter [hypoLES]) and patient demographic information, clinical characteristics, and autoantibody profiles were examined. Results: Ninety‐five patients with SSc had HREM data. Sixty‐five patients (68.4%) had AC (37 patients with only AC, 28 patients with AC and a hypoLES), 9 patients (9.5%) had IEM, and 11 patients (11.6%) had normal studies. AC was significantly associated with diffuse cutaneous disease (38.5% versus 10.0%; P < 0.01), more severe Raynaud's phenomenon, including digital pits, ulcers, or gangrene (56.9% versus 30.0%; P = 0.02), and reduced median diffusing capacity of lung for carbon monoxide (50.6% versus 72.2%; P = 0.03). AC was observed in most of the patients who died (13 of 14; P = 0.06). These findings were not seen in patients with IEM. Conclusion: Among patients with SSc, AC is associated with a significantly more severe clinical phenotype. IEM may associate with a milder phenotype. Further studies are needed to evaluate AC, IEM, and their clinical impact relative to the timing of other end‐organ complications in SSc. [ABSTRACT FROM AUTHOR]

Background: Whether esophagogastric junction outflow obstruction (EGJOO) is a variant of achalasia cardia (AC) or an esophageal motility state of certain organic or systemic diseases remains controversial. We aimed to investigate the differences between EGJOO and AC in clinical characteristics and outcomes through a 4-year follow-up. Methods: Patients diagnosed with primary EGJOO or AC were included. Based on the presence of concomitant disease, EGJOO patients were divided into a functional and an anatomical EGJOO group; similarly, patients with AC were divided into an AC with organic disease group and a true AC group. Disease characteristics and high-resolution manometry (HRM) parameters were retrospectively compared between the groups, and the development of organic diseases that could affect esophageal motility disorders and responses to treatment were examined during the follow-up. Symptom relief was defined as an Eckardt score of ≤3 after the treatment. Results: The study included 79 AC patients and 70 EGJOO patients. Compared with patients with AC, EGJOO patients were older, had shorter disease duration, a lower Eckardt score, and were more likely to have concurrent adenocarcinoma of the esophagogastric junction (AEG) and autoimmune disease (p < 0.05 for all). The severity of dysphagia and Eckardt scores were higher in the anatomical EGJOO group than in the functional EGJOO group. Significant differences were seen in HRM parameters (UES residual pressure, LES basal pressure, and LES residual pressure) between AC and EGJOO patients. However, no significant differences in HRM parameters were observed between the functional EGJOO and anatomical EGJOO groups. Sixty-seven (95.71%) patients with EGJOO and sixty-nine (87.34%) patients with AC experienced symptom relief (p = 0.071). Among patients achieving symptom relief, a relatively large proportion of patients with EGJOO had symptom relief after medications (37/67, 55.22%), the resolution of potential reasons (7/67, 10.45%), and spontaneous relief (15/67, 22.39%), while more patients with AC had symptom relief after POEM (66/69, 95.65%). Among EGJOO patients achieving symptom relief, more patients (7/20, 35%) with anatomical EGJOO had symptom relief after the resolution of potential reasons for EGJOO, while more patients (32/47, 68.09%) with functional EGJOO had symptom relief with medications. Conclusions: Concurrent AEG and autoimmune diseases are more likely in EGJOO than in AC. A considerable part of EGJOO may be the early manifestation of an organic disease. Anatomical EGJOO patients experience symptom improvement with the resolution of primary diseases, while most functional EGJOO patients experience symptom relief with pharmacotherapy alone or even without any treatment. [ABSTRACT FROM AUTHOR]

Background/Aims We aim to investigate the diagnostic accuracy and differences between Chicago classification version 3.0 (CC v3.0) and 4.0 (CC v4.0). Methods Patients who underwent high-resolution esophageal manometry (HRM) for suspected esophageal motility disorders were prospectively recruited between May 2020 and February 2021. The protocol of HRM studies included additional positional change and provocative testing designed by CC v4.0. Results Two hundred forty-four patients were included. The median age was 59 (interquartile range, 45-66) years, and 46.7% were males. Of these, 53.3% (n = 130) and 61.9% (n = 151) were categorized as normalcy by CC v3.0 and CC v4.0, respectively. The 15 patients diagnosed of esophagogastric junction outflow obstruction (EGJOO) by CC v3.0 was changed to normalcy by position (n = 2) and symptom (n = 13) by CC v4.0. In seven patients, the ineffective esophageal motility (IEM) diagnosis by CC v3.0 was changed to normalcy by CC v4.0. The diagnostic rate of achalasia increased from 11.1% (n = 27) to 13.9% (n = 34) by CC v4.0. Of patients diagnosed IEM by CC v3.0, 4 was changed to achalasia based on the functional lumen imaging probe (FLIP) results by CC v4.0. Three patients (2 with absent contractility and 1 with IEM in CC v3.0) were newly diagnosed with achalasia using a provocative test and barium esophagography by CC v4.0. Conclusions CC v4.0 is more rigorous than CC v3.0 for the diagnosis of EGJOO and IEM and diagnoses achalasia more accurately by using provocative tests and FLIP. Further studies on the treatment outcomes following diagnosis with CC v4.0 are needed. [ABSTRACT FROM AUTHOR]

Background/Aims Laryngeal symptoms are largely treated with empiric proton pump inhibitor (PPI) therapy if no apparent pathology shown on ear, nose, and throat evaluation and reflux-related etiologies are suspected. However, treatment response remains unsatisfactory. This study aimed to investigate the clinical and physiological characteristics of patients with PPI-refractory laryngeal symptoms. Methods Patients with persistent laryngeal symptoms despite PPI treatment for = 8 weeks were recruited. A multidisciplinary evaluation comprising validated questionnaires for laryngeal symptoms (reflux symptom index [RSI]), gastroesophageal reflux disease symptoms, psychological comorbidity (5-item brief symptom rating scale [BSRS-5]) and sleep disturbance (Pittsburgh sleep quality index [PSQI]), esophagogastroduodenoscopy, ambulatory impedance-pH monitoring, and high-resolution impedance manometry were performed. Healthy asymptomatic individuals were also recruited for comparison of psychological morbidity and sleep disturbances. Results Ninety-seven adult patients and 48 healthy volunteers were analyzed. The patients had markedly higher prevalence of psychological distress (52.6% vs 2.1%, P < 0.001) and sleep disturbance (82.5% vs 37.5%, P < 0.001) than the healthy volunteers. There were significant correlations between RSI and BSRS-5 scores, and between RSI and PSQI scores (r = 0.26, P = 0.010, and r = 0.29, P = 0.004, respectively). Fifty-eight patients had concurrent gastroesophageal reflux disease symptoms. They had more prominent sleep disturbances (89.7% vs 71.8%, P < 0.001) than those with laryngeal symptoms alone but similar reflux profiles and esophageal motility. Conclusions PPI-refractory laryngeal symptoms are mostly associated with psychological comorbidities and sleep disturbances. Recognition of these psychosocial comorbidities may help optimize management in these patients. [ABSTRACT FROM AUTHOR]

Gastroesophageal reflux disease (GERD) is a disorder due to the retrograde flow of refluxate into the esophagus. Although GERD is a common clinical diagnosis, its pathogenesis is quite complex. As a result of its multifactorial development, many patients continue to experience adverse symptoms due to GERD despite prolonged acid suppression with proton pump inhibitor therapy. The pathogenesis of GERD involves an interplay of chemical, mechanical, psychologic, and neurologic mechanisms, which contribute to symptom presentation, diagnosis, and treatment. As such, GERD should be approached as a disorder beyond acid. This review will investigate the major factors that contribute to the development of GERD, including factors related to the refluxate, esophageal defenses, and factors that promote pathologic reflux into the esophagus. In reviewing GERD pathogenesis, this paper will highlight therapeutic advances, with mention of future opportunities of study when approaching GERD.

Since publication of Chicago Classification version 3.0 in 2015, the clinical and research applications of high-resolution manometry (HRM) have expanded. In order to update the Chicago Classification, an International HRM Working Group consisting of 52 diverse experts worked for two years and utilized formally validated methodologies. Compared with the prior iteration, there are four key modifications in Chicago Classification version 4.0 (CCv4.0). First, further manometric and non-manometric evaluation is required to arrive at a conclusive, actionable diagnosis of esophagogastric junction (EGJ) outflow obstruction (EGJOO). Second, EGJOO, distal esophageal spasm, and hypercontractile esophagus are three manometric patterns that must be accompanied by obstructive esophageal symptoms of dysphagia and/or non-cardiac chest pain to be considered clinically relevant. Third, the standardized manometric protocol should ideally include supine and upright positions as well as additional manometric maneuvers such as the multiple rapid swallows and rapid drink challenge. Solid test swallows, postprandial testing, and pharmacologic provocation can also be considered for particular conditions. Finally, the definition of ineffective esophageal motility is more stringent and now encompasses fragmented peristalsis. Hence, CCv4.0 no longer distinguishes between major versus minor motility disorders but simply separates disorders of EGJ outflow from disorders of peristalsis.

Background: Dysphagia is a prevalent condition which may severely impact the patient’s quality of life. However, there are still lacking standardized therapeutic options for esophageal motility disorders. Summary: Dysphagia is defined as a subjective sensation of difficulty swallowing which can result from oropharyngeal or esophageal etiologies. Regarding esophageal dysphagia, after excluding structural causes and esophageal mucosal lesions, high-resolution manometry (HRM) is the gold standard for the diagnosis of esophageal motility disorders. HRM has not only improved the sensitivity for detecting achalasia but has also expanded our understanding of spastic and hypomotility disorders of the esophageal body. The Chicago Classification v4.0 uses a hierarchical approach and provides a standardized diagnosis of esophageal motility disorders, allowing a tailored therapeutic approach. Dysphagia is often a long-term health problem that broadly impacts health and well-being and leads to physical and psychosocial disability, namely, malnutrition and aspiration pneumonia, as well as social isolation, depression, and anxiety. Apart from achalasia, most esophageal motility disorders tend to have a benign long-term course with symptoms of dysphagia and noncardiac chest pain that can improve significantly over time. Patient-reported outcomes (PROs) are self-assessment tools that capture the patients’ illness experience and help providers better understand symptoms from the patients’ perspective. Therefore, PROs have a critical role in providing patient-centered care. Key Messages: Motility disorders should be ruled out in the presence of nonobstructive esophageal dysphagia, and treatment options should be considered according to the severity of symptoms reported by the patient.

Objectives Current gold standard investigations to determine the pathology of ineffective esophageal motility (IEM) are invasive and resource-intensive. Marshmallow barium swallow esophagogram (MBSE) is emerging as a more feasible modality; however, our understanding of its role in the clinical setting is limited. Our aim was to appraise the current literature and describe the effectiveness and limitations of MBSE as a potential diagnostic tool when investigating the pathological cause of IEM. Methods A search in PubMed was conducted on May 23, 2021. Search terms included “marshmallow” AND “barium.” We included all studies which examined MBSE in the context of esophageal disease. The primary outcome of interest was to characterize the use of MBSE in current literature. Results A total of 12 studies were retrieved after initial search with 9 studies meeting final inclusion criteria. A total of 375 patients were included, with 296 patients (79%) having a relevant diagnosis or symptom prompting investigation with MBSE. The most common diagnoses included referral to a gastroenterology clinic for a barium swallow (44%), post-Angelchik insertion (23%), and dysphagia (13%). Esophageal disease was identified in both the MBSE and other screening tests in 63% participants, whereas in 27% participants abnormalities were only seen using the MBSE. Conclusion There is currently limited high-quality evidence on the use of MBSE to diagnose IEM. Further large-scale studies comparing its use in patients with different pathologic causes of IEM and of older age are required to further delineate the optimal delivery of this emerging diagnostic modality.

Background: Esophageal motility disorders are a group of disorders associated with dysfunctional swallowing resulting from impaired neuromuscular coordination. Phosphodiesterase 5 (PDE-5) inhibitors induce smooth relaxation and are proposed as a treatment option for esophageal motility disorders such as achalasia. Methods: This study is conducted based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). We systematically searched MEDLINE/ PubMed, Scopus, EMBASE, and Web of Science databases for esophageal outcomes of individuals treated with PDE5 inhibitors. A random effect meta-analysis was conducted. Results: A total of 14 studies were included. They were conducted in different countries, with Korea and Italy having the highest number of articles. The main drug assessed was sildenafil. PDE-5 inhibitors resulted in a significant reduction in lower esophageal sphincter pressure (SMD − 1.69, 95% CI: -2.39 to -0.99) and the amplitude of contractions (SMD − 2.04, 95% CI: -2.97 to -1.11). Residual pressure was not significantly different between the placebo and sildenafil groups (SMD − 0.24, 95% CI: -1.20 to 0.72). Furthermore, a recent study reported contractile integral, stating that ingestion of sildenafil leads to a significant reduction in distal contractile integral and a significant increase in proximal contractile integral. Conclusion: PDE-5 inhibitors significantly reduce LES resting pressure and esophageal peristaltic vigor, decreasing esophageal body contractility and contraction reserve. Therefore, using these drugs in patients affected by esophageal motility disorders may potentially improve their condition regarding symptom relief and prevention of further associated complications. Future reports investigating larger sample size is necessary in order to establish definite evidence regarding the efficacy of these drugs. [ABSTRACT FROM AUTHOR]

Systemic sclerosis (SSc) is often associated with dysphagia and esophageal dysmotility; however, only a few clinical studies on this topic have been conducted. Patients with SSc who underwent swallowing examinations and esophagography at our institution between 2010 and 2022 were included. A retrospective evaluation of the patients' backgrounds, autoantibody positivity, swallowing function, and esophageal motility was performed using medical charts. The association between dysphagia and esophageal dysmotility in patients with SSc and respective risk factors was investigated. Data were collected from 50 patients. Anti-topoisomerase I antibodies (ATA) and anti-centromere antibodies (ACA) were detected in 21 (42%) and 11 (22%) patients, respectively. Dysphagia was present in 13 patients (26%), and esophageal dysmotility in 34 patients (68%). ATA-positive patients had a higher risk for dysphagia (p = 0.027); ACA-positive patients had a significantly lower risk (p = 0.046). Older age and laryngeal sensory deficits were identified as risk factors for dysphagia; however, no risk factors for esophageal dysmotility were identified. No correlation was found between dysphagia and esophageal dysmotility. Esophageal dysmotility is more common in patients with SSc than in those with dysphagia. Autoantibodies can be predictors of dysphagia, and dysphagia must be carefully considered in ATA-positive and elderly patients with SSc. [ABSTRACT FROM AUTHOR]

Introduction: Limited information is available regarding the clinical and manometric characteristics of different subtypes of achalasia. This study aims to describe these characteristics in patients treated at a prominent hospital in Colombia. Methods: This descriptive observational study included patients diagnosed with achalasia using high-resolution esophageal manometry at Hospital Universitario San Ignacio in Bogotá, Colombia, between 2016 and 2020. We documented the clinical manifestations, manometric findings, treatment approaches, and response to treatment based on the subtype of achalasia. Results: A total of 87 patients were enrolled, with a median age of 51 years, and 56.4% of them were female. The majority had type II achalasia (78.1%), followed by type I (16%) and type III (5.7%). All patients presented with dysphagia, 40.2% experienced chest pain, and 27.6% had gastroesophageal reflux. The clinical parameters, including integrated relaxation pressure value (IRP; median: 24 mmHg, interquartile range [IQR]: 19-33), upper esophageal sphincter pressure (UES; median: 63 mmHg, IQR: 46-98), and lower esophageal sphincter pressure (LES; median: 34 mm Hg, IQR: 26-45), were similar across the different subtypes. Esophageal clearance was incomplete in all patients. Among the 35 patients who received intervention, Heller's myotomy was the most commonly employed procedure (68.5%), followed by esophageal dilation (28.6%). All patients experienced symptomatic improvement, with a median pre-treatment Eckardt score of 5 (IQR: 5-6) and a post-treatment score of 1 (IQR: 1-2). Conclusions: Type II achalasia is the most prevalent subtype. The clinical and manometric findings, as well as treatment response, exhibit similarities among the different subtypes of achalasia. In Colombia, the outcomes of this condition align with those reported in other parts of the world. [ABSTRACT FROM AUTHOR]

Systemic sclerosis (SSc) is an immune-mediated connective tissue disease. Recent studies reported differences in the composition of intestinal microbiota (dysbiosis) in patients with SSc compared to nonsclerodermic subjects. Dysbiosis may disrupt the intestinal barrier, which leads to immunological activation via microbial antigen and metabolite translocation. The study aimed to assess the differences in intestinal permeability between SSc patients and controls and to examine the correlation between intestinal permeability and complications of SSc. The study comprised 50 patients with SSc and 30 matched subjects. Serum intestinal permeability markers: intestinal fatty acid binding protein, claudin-3, and lipopolysaccharides (LPS) were determined using an enzyme-linked immunosorbent assay. SSc patients had a significantly increased concentration of LPS compared to control subjects (232.30 [149.00–347.70] versus 161.00 [83.92–252.20] pg/mL, p < 0.05). The patients with shorter SSc duration (≤6 years) had an increased concentration of LPS and claudin-3 compared to the subgroup with longer disease length: LPS (280.75 [167.30–403.40] versus 186.00 [98.12–275.90] pg/mL, p < 0.05), and claudin-3 (16.99 [12.41–39.59] versus 13.54 [10.29–15.47] ng/mL, p < 0.05). The patients with esophageal dysmotility had a decreased LPS level compared to those without this complication (188.05 [102.31–264.40] versus 283.95 [203.20–356.30] pg/mL, p < 0.05). Increased intestinal permeability in SSc may exacerbate the course of the disease and increase the risk of developing complications. Lower LPS levels in SSc might be a hallmark of esophageal dysmotility. [ABSTRACT FROM AUTHOR]

Background: Although swallowing disorders can impact individuals of any age, some are unique to the elderly, and others are frequent. Some disorders, such as achalasia, are diagnosed by esophageal manometry studies, which assess lower esophageal sphincter (LES) pressure and relaxation, peristalsis in the esophageal body, and contraction wave characteristics. This research aimed to evaluate esophageal motility dysfunction in symptomatic patients and its relation to age. Methods: Conventional esophageal manometry was performed on 385 symptomatic patients who were divided into two groups; Group A (age < 65 years old) and Group B (age ≥ 65 years). The geriatric assessment for Group B included cognitive, functional, and clinical frailty scales (CFS). Additionally, a nutritional assessment was done for all patients. Results: About one-third of the patients (33%) had achalasia, in which manometric results were significantly higher in Group B (43.4%) than in Group A (28.7%) (P = 0.016). The resting lower esophageal sphincter (LES) pressure, as determined by manometry examination, was significantly lower in Group A than in Group B. In contrast, complete LES relaxation percentage and normal esophageal body peristalsis were significantly higher in Group A than in Group B. Patients who exhibited evidence of achalasia in the manometric study had a significantly increased risk of established malnutrition and functional impairment. Conclusions: Achalasia is a prevalent cause of dysphagia in elderly patients, placing them at risk of malnutrition and functional impairment. Thus, a multidisciplinary approach is vital when providing care for this population. [ABSTRACT FROM AUTHOR]

The article discusses Gastroesophageal reflux disease (GERD) is a gastrointestinal disorder affecting 8 to 33% of people worldwide, which can lead to severe complications including esophageal strictures, Barrett's esophagus, and even esophageal cancer. Electrical stimulation therapy (EST) is a promising method to treat GERD; however, the implantation of conventional EST devices can be invasive and carries potential risks.

Background: The effects of Helicobacter pylori (HP) eradication on gastroesophageal reflux disease (GERD) are yet to be fully elucidated. Few studies have investigated the mechanisms underlying the correlations between HP and GERD with prospective methods. The objective of this prospective clinical study was to explore the effects of HP eradication on GERD. Methods: Patients diagnosed with both GERD and HP were included. High-resolution esophageal manometry (HRM), 24-h esophageal pH monitoring, and the Gastroesophageal Reflux Disease Questionnaire (GerdQ) were performed before and after the successful eradication of HP, and the data were compared using statistical analysis. Results: Sixty-eight patients diagnosed with both GERD and HP were included. The After HP eradication group showed significantly decreased median distal contractile integral (DCI) [610.40 (847.45) vs. 444.90 (559.60)] and significantly increased median inefficient esophageal motility (IEM) [36.00 (50.00) vs. 60.00 (57.00)] in the HRM compared with those of the Before HP eradication group, indicating that HP eradication reduced esophageal peristalsis. The 24-h esophageal pH monitoring showed that the longest reflux event, the percentage of time that the pH was <4, the number of reflux episodes, and the DeMeester score were all significantly different between the Before and After HP eradication groups (P < 0.05), suggesting that HP eradication increased esophageal acid exposure. The After HP eradication group also had a significantly higher GerdQ score than that of the Before HP eradication group (P < 0.05). Conclusions: HP eradication reduced esophageal peristalsis, enhanced esophageal acid exposure, and aggravated GERD symptoms, suggesting that HP infection may be a protective factor for GERD. [ABSTRACT FROM AUTHOR]

Purpose: A retrospective study is presented to correlate the inter-judge consistency for the different psycho-perceptual parameters of the recently proposed Impression Noise Fluency Voicing (INFVo) perceptual rating scale for substitution voices, and the vocal function as perceived by the patient. Methods: The scale Voice-Related Quality of Life (V-RQoL) and the Self Evaluation of Communication Experiences After Laryngectomy scale (SECEL)—a self-evaluation questionnaire of communicative experience after laryngectomy surgery—were administered to 89 total laryngectomees, subdivided in four groups depending on their type of alaryngeal voice (i.e., tracheoesophageal and esophageal speakers, electro larynx users, voiceless patients), in order to evaluate the impact of the impairment of the phonatory function on the quality of life. Results: No significant differences exist among the various groups on their perception of QoL using subjective questionnaires, whereas the INFVo scale has proven to be a useful tool for the description and analysis of the psychoacoustic characteristics of the vocal signal and a reliable instrument to correctly classify the patients. It is also notable that the judgement of the patients on their own voice and those of the referees are highly significant. Conclusion: Although speech rehabilitation for the acquisition of a substitution voice offers a new way of communication for the laryngectomized patients, nonetheless, their QoL is not significantly related to the type of substitution voice. Therefore, improving the patient's adaptation to the new phonatory condition is mandatory. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to investigate the relationships of serum folate (vitamin B9), cobalamin (vitamin B12) levels and diet with semen parameters (semen standard parameters [SSP] and DNA fragmentation index [DFI]) in infertile men. Methods: Sperm samples were assessed for SSP and DFI (using the sperm chromatin dispersion test). Serum vitamin concentrations were measured with an immuno-electrochemiluminescence assay, and men completed a semi-quantitative food frequency questionnaire (FFQ). Results: Serum folate levels were positively correlated with sperm progressive motility and DFI. A comparison of SSP between two groups of patients according to serum folate concentration (B9 <4.840 ng/mL and B9 =4.840 ng/mL) showed significantly higher sperm concentration and sperm progressive motility in the latter group. However, there was no difference between these groups regarding DFI. Interestingly, serum folate levels were significantly higher in patients with a high DFI (using the cut-offs of 30% or 18%). FFQ data showed that the consumption of fruits and egg yolk correlated positively with sperm concentration and sperm motility, respectively. Conclusion: Serum folate levels showed significant associations with sperm concentration and sperm progressive motility. However, the positive association of serum folate with DFI raises the need for careful prescription of folate supplements. [ABSTRACT FROM AUTHOR]