Effect of a Gluten-Free Diet on Whole Gut Transit Time in Celiac Disease (CD) and Non-Celiac Gluten Sensitivity (NCGS) Patients: A Study Using the Wireless Motility Capsule (WMC).

Background: This study explores the impact of a gluten-free diet (GFD) on regional gastrointestinal (GI) transit times in individuals with celiac disease (CD) and non-celiac gluten sensitivity (NCGS). While a GFD is established for managing CD and wheat allergy, its effects on NCGS remain controversial due to inconclusive evidence. Methods: Utilizing a wireless motility and pH capsule (WMC) to assess regional (measurements of gastric, small bowel, and colonic transit times) and whole gut transit, newly diagnosed CD (n = 12) and NCGS (n = 12) patients underwent evaluations at baseline and 4 weeks after having a GFD. Results: At baseline conditions, individuals diagnosed with CD exhibited prolonged colonic and intestinal transit times when compared to those with NCGS (p < 0.05). Following a 4-week GFD, CD patients experienced significant reductions in both intestinal and colonic transit times, along with enhanced small intestine contractility. NCGS individuals showed improvements in intestinal transit time and contractility with a GFD, although the colon exhibited no discernible effect. The GFD did not significantly impact intragastric, intestinal, or colonic pH. Conclusions: This study, employing WMC for the first time, provides novel insights into the positive effects of a GFD on intestinal and colonic transit, as well as contractility, in CD patients, and to a lesser extent, in those with NCGS.

Efficacy of the regional Mexican diet versus the Mediterranean diet in patients with MASLD: a 24-week non-inferiority trial.

In the present manuscript we present evidence of the improvement of MASLD with dietary intervention. It is known that the Mediterranean diet is the best intervention for this pathology, however, it cannot be established in all countries due to the diversity of foods. We create a Mexican diet with the nutrients of the Mediterranean diet for the treatment of our population.

Association of adverse childhood experiences with irritable bowel syndrome in Mexican adults: A cross-sectional study.

BACKGROUND: Adverse childhood experiences (ACEs) are linked to the development of gastrointestinal disorders during adulthood, but there is limited research on the prevalence of ACEs in Latin American populations. This study aimed to assess the prevalence and impact of ACEs on Mexican adults with irritable bowel syndrome (IBS). METHODS: In this cross-sectional study, we recruited 290 Mexican adults (aged 18-65), including 90 individuals with IBS and 200 healthy controls. All participants completed four self-reported questionnaires: The Adverse Childhood Experiences Questionnaire (ACEs), Visceral Sensitivity Index, Irritable Bowel Syndrome Symptom Severity Scale, and Hospital Anxiety and Depression Scale. Statistical analyses included mean differences using either the Student's t-test or the Wilcoxon test, correlations assessed with Spearman's correlation coefficient, and logistic regression models. Statistical significance was defined as a p-value less than 0.05. KEY RESULTS: Among IBS subjects, the prevalence of ACEs was 80%, significantly higher than the 59% prevalence observed in controls (p < 0.0001). Individuals with ACEs exhibited elevated levels of anxiety and depression. Seventy-five percent of IBS subjects with severe symptoms reported four or more ACEs. The presence of four or more ACEs was found to be associated with an increased risk of IBS. CONCLUSIONS AND INFERENCES: ACEs are notably prevalent among Mexican individuals with IBS and are positively correlated with the severity of gastrointestinal pain. These findings underscore the critical significance of evaluating and addressing ACEs in the comprehensive management of IBS within Latin American populations.

Updates to the modern diagnosis of GERD: Lyon consensus 2.0.

The Lyon Consensus provides conclusive criteria for and against the diagnosis of gastro-oesophageal reflux disease (GERD), and adjunctive metrics that consolidate or refute GERD diagnosis when primary criteria are borderline or inconclusive. An international core and working group was assembled to evaluate research since publication of the original Lyon Consensus, and to vote on statements collaboratively developed to update criteria. The Lyon Consensus 2.0 provides a modern definition of actionable GERD, where evidence from oesophageal testing supports revising, escalating or personalising GERD management for the symptomatic patient. Symptoms that have a high versus low likelihood of relationship to reflux episodes are described. Unproven versus proven GERD define diagnostic strategies and testing options. Patients with no prior GERD evidence (unproven GERD) are studied using prolonged wireless pH monitoring or catheter-based pH or pH-monitoring off antisecretory medication, while patients with conclusive GERD evidence (proven GERD) and persisting symptoms are evaluated using pH-impedance monitoring while on optimised antisecretory therapy. The major changes from the original Lyon Consensus criteria include establishment of Los Angeles grade B oesophagitis as conclusive GERD evidence, description of metrics and thresholds to be used with prolonged wireless pH monitoring, and inclusion of parameters useful in diagnosis of refractory GERD when testing is performed on antisecretory therapy in proven GERD. Criteria that have not performed well in the diagnosis of actionable GERD have been retired. Personalisation of investigation and management to each patient's unique presentation will optimise GERD diagnosis and management.

Prevalence of Anti- Saccharomyces Cerevisiae Antibodies (ASCA) in Patients With Irritable Bowel Syndrome (IBS). A Case-control Study.

BACKGROUND: Irritable bowel syndrome (IBS) is a disorder of gut-brain interaction that affects patients' quality. Recent research has shown variations in the mycobiome of individuals with IBS, particularly involving Saccharomyces cerevisiae , and its association with dysbiosis and visceral hypersensitivity. However, the role of Anti-Saccharomyces cerevisiae antibodies (ASCA) in IBS remains unclear, despite their significance as markers of disease severity in inflammatory bowel disease. OBJECTIVE: This study aimed to investigate the role of ASCA in Mexican IBS patients compared with healthy controls (HCs) and determine whether these antibodies could help differentiate between IBS patients and healthy individuals. METHODS: Serum samples from 400 IBS patients and 400 HC were analyzed. ASCA IgG levels were measured using enzyme-linked immunosorbent assay (ELISA). The IBS patients were further categorized into subtypes: constipation predominant (IBS-C), diarrhea predominant (IBS-D), and mixed (IBS-M). RESULTS: Among the participants, 66 IBS patients (16.5%) and 63 HC (15.75%) tested positive for ASCA IgG. No significant difference was observed in ASCA IgG levels between the 2 groups ( P value: 0.8451). The prevalence of ASCA IgG positivity was 14.5% in IBS-C, 17.8% in IBS-D, and 15.9% in IBS-M. CONCLUSION: Surprisingly, a high prevalence of ASCA IgG was found in the HC group in Mexico. Furthermore, there was no significant difference in ASCA IgG levels between IBS patients and controls. These findings suggest that ASCA is not useful as a discriminatory biomarker for distinguishing IBS patients from healthy individuals and cannot serve as a surrogate marker for visceral hypersensitivity.

Incidence of Small Intestinal Bacterial Overgrowth and Symptoms After 7 Days of Proton Pump Inhibitor Use: A Study on Healthy Volunteers.

INTRODUCTION: Proton pump inhibitors (PPIs) are commonly prescribed drugs. Chronic PPI use has recently been associated with the risk for developing small intestinal bacterial overgrowth (SIBO). It is not known whether the short-term prescription of a PPI can trigger SIBO. Therefore, the aim of the present study was to evaluate the incidence of SIBO and gastrointestinal symptoms after 7 days of PPI use. MATERIALS AND METHODS: A prospective, pilot, open-label study was conducted on asymptomatic healthy volunteers. The incidence of SIBO was evaluated at the baseline and after administration of 40 mg of pantoprazole once a day for 7 days, through a glucose breath test. In addition, the presence of gastrointestinal symptoms, the number of bowel movements, and the consistency of stools, according to the Bristol scale, were assessed. RESULTS: Thirty-eight healthy subjects (71.1% women, mean age 25.18 ± 6.5 years) were analyzed. The incidence of SIBO after 7 days of PPI administration was 7.8% (95% CI 1.6-21.3%). The patients that developed SIBO had a greater prevalence of bloating (p = 0.0002) and flatulence (p = 0.004) after 7 days of treatment. CONCLUSIONS: Our study showed that a short-term 7-day PPI course produced SIBO in 7.8% of healthy subjects. Although, inappropriate use of PPIs should be discouraged, but since more than 90% of subjects who received PPIs for one week did not develop SIBO, the advantages of PPI administration seem to outweigh the disadvantages.

Aflatoxin exposure in adults in southern and eastern Mexico in 2018: A descriptive study.

OBJECTIVE: To estimate the frequency of detection and levels of aflatoxin B1-lysine adduct (AFB1-lys), an important hepatocellular carcinoma (HCC) risk factor, in eastern and southern Mexico. MATERIALS AND METHODS: We determined serum AFB1-lys using mass spectrometry in a representative sample of 952 adults (weighted n = 7,493,354) from five states (Campeche, Chiapas, Tamaulipas, Veracruz and Yucatán) in 2018. We calculated overall and subgroup-specific frequency of detection and 95% confidence intervals (95%CI) and median AFB1-lys levels and quartiles. RESULTS: The overall frequency of detection of AFB1-lys was 91.9% (95%CI 88.6, 94.3). The median AFB1-lys level was 0.172 pg/µL (Q1-Q3, 0.060-0.582). Levels differed geographically (median pg/µL, 0.361 for Veracruz and 0.061 for Yucatan) and were higher among men and older individuals. Levels were almost three times higher in rural relative to urban areas (0.317 vs. 0.123 pg/µL). We observed higher AFB1-lys exposure in lower socioeconomic status (SES) level populations. CONCLUSION: AFB1-lys frequency of detection was very high and exposure levels were highest in Veracruz, men, rural areas, and among persons of lower SES. Understanding modifiable HCC risk factors in populations with unique epidemiological patterns could inform preventative interventions.

Contribution of MicroRNAs in the Development of Irritable Bowel Syndrome Symptoms.

Irritable bowel syndrome (IBS) is a common chronic functional gastrointestinal disorder defined by disturbances in bowel habits and abdominal pain, in the absence of known organic pathology that affects between 5 to 10% of healthy populations. Despite improvements in detection and treatment, the pathogenesis of IBS has not been clarified. Several microRNAs (miRNAs) are involved in the pathogenesis of IBS through increased intestinal permeability, inflammation, and modulation of visceral hyperalgesia, and they may have the potential to be used as biomarkers and therapeutic targets. Here, we have summarized the recent advances about the role of miRNAs in the development of IBS symptoms and the possibility to use them as therapeutic targets to mitigate symptoms in IBS.

Update on the Role of Rifaximin in Digestive Diseases.

Various environmental factors affecting the human microbiota may lead to gut microbial imbalance and to the development of pathologies. Alterations of gut microbiota have been firmly implicated in digestive diseases such as hepatic encephalopathy, irritable bowel syndrome and diverticular disease. However, while these three conditions may all be related to dysfunction of the gut-liver-brain axis, the precise pathophysiology appears to differ somewhat for each. Herein, current knowledge on the pathophysiology of hepatic encephalopathy, irritable bowel syndrome, and diverticular disease are reviewed, with a special focus on the gut microbiota modulation associated with these disorders during therapy with rifaximin. In general, the evidence for the efficacy of rifaximin in hepatic encephalopathy appears to be well consolidated, although it is less supported for irritable bowel syndrome and diverticular disease. We reviewed current clinical practice for the management of these clinical conditions and underlined the desirability of more real-world studies to fully understand the potential of rifaximin in these clinical situations and obtain even more precise indications for the use of the drug.

Obesity Contributes to Inflammation in Patients with IBS via Complement Component 3 and C-Reactive Protein.

Irritable Bowel Syndrome (IBS) is usually a lifelong state that disturbs the digestive system. IBS has been linked to low-grade inflammation and the release of inflammatory mediators into the bloodstream. This could be associated with the degree of obesity presented by patients with IBS. Reports imply that IBS is more frequent in obese patients than in the overall population, with a prevalence of up to 31%. Here, we evaluated the serum levels of immunological and inflammation molecules and their correlation with Body Mass Index in IBS patients and the healthy control (HC). Seventy-nine serum samples of the IBS patients and thirty-five of the HC group were analyzed to determine the levels of each molecule and compare them with their BMI. Serum levels of C3 and C4 were significantly increased in IBS patients. C3 and C4 levels were higher in IBS-M and IBS-D subtypes compared with the HC group. When patients were grouped by BMI, a positive correlation between serum C3 (r = 0.49, p < 0.0001) and CRP (r = 0.40, p < 0.001) levels was found. Our results show, for the first time, a correlation between immunological molecules and BMI in IBS patients, suggesting that the inflammatory nature of obesity could contribute to the development of the symptoms in IBS through the stimulation and release of proteins as complement components and CRP.

Higher cardiovascular risk scores and liver fibrosis risk estimated by biomarkers in patients with metabolic-dysfunction-associated fatty liver disease.

BACKGROUND: The definition of metabolic-dysfunction-associated fatty liver disease (MAFLD) allows identification of metabolically complicated patients. Fibrosis risk scores are related to cardiovascular risk (CVR) scores and could be useful for the identification of patients at risk of systemic complications. AIM: To evaluate the relationship between MAFLD and CVR using the Framingham risk score in a group of Mexican patients. METHODS: Cross-sectional, observational and descriptive study carried out in a cohort of 585 volunteers in the state of Veracruz with MAFLD criteria. The risk of liver fibrosis was calculated with aspartate aminotransferase-to-platelet ratio index, nonalcoholic fatty liver disease score and fibrosis-4, as well as with transient hepatic elastography with Fibroscan®. The CVR was determined by the Framingham system. RESULTS: One hundred and twenty-five participants (21.4%) with MAFLD criteria were evaluated, average age 54.4 years, 63.2% were women, body mass index 32.3 kg/m2. The Framingham CVR was high in 43 patients (33.9%). Transient elastography was performed in 55.2% of volunteers; 39.1% with high CVR and predominance in advanced fibrosis (F3-F4). The logistic regression analysis showed that liver fibrosis, diabetes and hypertension independently increased CVR. CONCLUSION: One of every three patients with MAFLD had a high CVR, and in those with high fibrosis risk, the CVR risk was even greater.

The Brief Esophageal Dysphagia Questionnaire shows better discriminative capacity for clinical and manometric findings than the Eckardt score: Results from a multicenter study.

INTRODUCTION: Grading dysphagia is crucial for clinical management of patients. The Eckardt score (ES) is the most commonly used for this purpose. We aimed to compare the ES with the recently developed Brief Esophageal Dysphagia Questionnaire (BEDQ) in terms of their correlation and discriminative capacity for clinical and manometric findings and evaluate the effect of gastroesophageal reflux symptoms on both. METHODS: Symptomatic patients referred for high-resolution manometry (HRM) were prospectively recruited from seven centers in Spain and Latin America. Clinical data and several scores (ES, BEDQ, GERDQ) were collected and contrasted to HRM findings. Standard statistical analysis was performed. KEY RESULTS: 426 patients were recruited, 31.2% and 41.5% being referred exclusively for dysphagia and GERD symptoms, respectively. Both BEDQ and ES were independently associated with achalasia. Only BEDQ was independently associated with being referred for dysphagia and with relevant HRM findings. ROC curve analysis for achalasia diagnosis showed AUC of 0.809 for BEDQ and 0.765 for ES, with the main difference being higher BEDQ sensitivity (80.0% vs 70.8% for ES). GERDQ independently predicted ES but not BEDQ. In the absence of dysphagia (BEDQ = 0), GERD symptoms significantly determine ES. CONCLUSIONS AND INFERENCES: Our study suggests both the BEDQ and ES can complementarily describe symptomatic burden in achalasia. BEDQ has several advantages over the ES in the dysphagia evaluation, basically due to its higher sensitivity for manometric diagnosis and independence of GERD symptoms. ES should be used as an achalasia-specific metric, while BEDQ is a better symptom-generic evaluating tool.

Psyllium reduces inulin-induced colonic gas production in IBS: MRI and in vitro fermentation studies.

OBJECTIVE: Health-promoting dietary fibre including inulin often triggers gastrointestinal symptoms in patients with IBS, limiting their intake. Our aim was to test if coadministering psyllium with inulin would reduce gas production. DESIGN: A randomised, four-period, four-treatment, placebo-controlled, crossover trial in 19 patients with IBS. Subjects ingested a 500 mL test drink containing either inulin 20 g, psyllium 20 g, inulin 20 g+ psyllium 20 g or dextrose 20 g (placebo). Breath hydrogen was measured every 30 min with MRI scans hourly for 6 hours. Faecal samples from a subset of the patients with IBS were tested using an in vitro fermentation model. Primary endpoint was colonic gas assessed by MRI. RESULTS: Colonic gas rose steadily from 0 to 6 hours, with inulin causing the greatest rise, median (IQR) AUC(0-360 min) 3145 (848-6502) mL·min. This was significantly reduced with inulin and psyllium coadministration to 618 (62-2345) mL·min (p=0.02), not significantly different from placebo. Colonic volumes AUC(0-360 min) were significantly larger than placebo for both inulin (p=0.002) and inulin and psyllium coadministration (p=0.005). Breath hydrogen rose significantly from 120 min after inulin but not psyllium; coadministration of psyllium with inulin delayed and reduced the maximum increase, AUC(0-360 min) from 7230 (3255-17910) ppm·hour to 1035 (360-4320) ppm·hour, p=0.007.Fermentation in vitro produced more gas with inulin than psyllium. Combining psyllium with inulin did not reduce gas production. CONCLUSIONS: Psyllium reduced inulin-related gas production in patients with IBS but does not directly inhibit fermentation. Whether coadministration with psyllium increases the tolerability of prebiotics in IBS warrants further study. TRIAL REGISTRATION NUMBER: NCT03265002.

Body composition and phase angle by bioimpedance in patients with MAFLD. / Análisis de la composición corporal y ángulo de fase por bioimpedancia en pacientes con MAFLD.

OBJECTIVE: To describe the characteristics of the body components and phase angle (PhA) of patients with MAFLD according to those different to fibrosis and hepatic steatosis. MATERIAL AND METHODS: Observational and descriptive study in a cohort of 585 volunteers from our center with MAFLD criteria. The risk of liver fibrosis was determined by APRI, NAFLD score and FIB-4; at an indeterminate and high risk of fibrosis, a transient elastography (Fibroscan®) were realized. Bioimpedance body composition analysis (SECA®) was performed. Patients with ET and SECA® registry were included. Bioimpedance body composition analysis (SECA®) was performed. Patients with ET and SECA® registry were included. RESULTS: 125 participants (21.4%) were evaluated, age 53.9±13.9 years, 62.1% women, BMI 33.2±5.8kg/m2. The SECA® analysis showed mean fat mass of 42%±7.32 and muscle mass 21.18kg±6.6. The PhA was 5.1±0.69, in women 4.92±0.62 and men 5.41±0.70. PhA in patients without fibrosis was 5.091 vs with fibrosis 5.121 (P=.813). In advanced fibrosis, it reported a low value compared to the rest of the groups (P=.031). The PhA in S3 was higher compared to S1 and S2 (5.3 vs 4.82, 4.81) (P=.027). CONCLUSIONS: In MAFLD, the PhA was lower than the healthy Mexican population. In patients without fibrosis and severe steatosis, PhA rises proportionally to the increase in fat mass and BMI and in advanced liver fibrosis, PhA decreases.

The Liver and COVID-19 in Mexico.

Content available: Author Interview and Audio Recording.

Incidence of 'new-onset' constipation and associated factors during lockdown due to the COVID-19 pandemic.

OBJECTIVE: A minimum of physical activity and low liquid intake are factors that have been associated with constipation. The health emergency brought on by the COVID-19 pandemic has resulted in adopting behaviour, such as sheltering-in-place (less mobility) and dietary changes, creating a scenario we believe to be an adequate model for examining the appearance of symptoms of constipation and its associated factors. DESIGN: A cross-sectional and descriptive study was conducted on an open population, applying an electronic survey (4 weeks after lockdown due to COVID-19 in Mexico) to evaluate demographic characteristics, physical activity, water and fibre intake, appearance of constipation symptoms (including stool consistency), and quality of life. RESULTS: Out of 678 subjects evaluated, 170 (25%, 95% CI: 21.7 to 28.4) developed symptoms of 'new-onset' constipation, with a significant decrease in the number of daily bowel movements (p<0.05) and stool consistency (p<0.05) during lockdown. Furthermore, in the 'new-onset' constipation population there was a higher proportion of subjects (79 (47%) of 170) who stopped exercising during the pandemic compared with the subjects who did not develop constipation symptoms (187 (37%) of 508, p=0.03, OR: 1.49, 95% CI: 1.0 to 2.1). The multivariate analysis (logistic regression) showed that female sex (p=0.001), water intake (p=0.039), and physical activity (p=0.012) were associated with 'new-onset' constipation. CONCLUSIONS: In our study on an open population in Mexico, we found that one-fourth of the population developed 'new-onset' constipation symptoms during the lockdown imposed due to the COVID-19 pandemic. A reduction of physical activity and less water consumption were associated factors.

The Prevalence of Anti-Zein Antibodies: A Comparative Study between Celiac Disease and Irritable Bowel Syndrome.

Celiac disease (CD) is a chronic immune-mediated enteropathy triggered by exposure to dietary gluten in genetically predisposed individuals. In contrast, irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder affecting the large intestine, without an autoimmune component. Here, we evaluated the prevalence of IgA and IgG antibodies to maize zeins (AZA) in patients with CD and IBS. Using an in-house ELISA assay, the IgA and IgG anti-zein antibodies in the serum of 37 newly diagnosed CD (16 biopsy proved and 21 serological diagnosis) and 375 IBS patients or 302 healthy control (HC) subjects were measured. Elevated levels of IgA AZA were found in CD patients compared with IBS patients (p < 0.01) and HC (p < 0.05). CD patients had the highest prevalence (35.1%), followed by IBS (4.3%) and HCs (2.3%) (p < 0.0001). IgG AZA antibodies were not found in any CD patients, IBS patients, or HC subjects. A significant positive correlation was found between IgA AZA with IgA anti-gliadin (AGA, r = 0.34, p < 0.01) and IgA anti-deaminated gliadin peptides (DGP, r = 0.42, p < 0.001) in the celiac disease group. Taken together, our results show for the first time a higher prevalence of AZA IgA antibodies in newly diagnosed CD patients than in IBS patients, confirming a biased immune response to other gliadin-related prolamins such as maize zeins in genetically susceptible individuals.

The Spanish version of the esophageal hypervigilance and anxiety score shows strong psychometric properties: Results of a large prospective multicenter study in Spain and Latin America.

BACKGROUND: Anxiety is a significant modulator of sensitivity along the GI tract. The recently described Esophageal Hypervigilance and Anxiety Score (EHAS) evaluates esophageal-specific anxiety. The aims of this study were as follows: 1. translate and validate an international Spanish version of EHAS. 2. Evaluate its psychometric properties in a large Hispano-American sample of symptomatic individuals. METHODS: A Spanish EHAS version was developed by a Delphi process and reverse translation. Patients referred for high-resolution manometry (HRM) were recruited prospectively from seven Spanish and Latin American centers. Several scores were used: EHAS, Hospital Anxiety and Depression Scale (HADS), Eckardt score (ES), Gastroesophageal Reflux Questionnaire (GERDQ), and the Brief Esophageal Dysphagia Questionnaire (BEDQ). Standardized psychometric analyses were performed. KEY RESULTS: A total of 443 patients were recruited. Spanish EHAS showed excellent reliability (Cronbach´s alpha = 0.94). Factor analysis confirmed the presence of two factors, corresponding to the visceral anxiety and hypervigilance subscales. Sufficient convergent validity was shown by moderate significant correlations between EHAS and other symptomatic scores. Patients with high EHAS scores had significantly more dysphagia. There was no difference in EHAS scores when compared normal vs abnormal or major manometric diagnosis. CONCLUSIONS AND INFERENCES: A widely usable Spanish EHAS version has been validated. We confirm its excellent psychometric properties in our patients, confirming the appropriateness of its use in different populations. Our findings support the appropriateness of evaluating esophageal anxiety across the whole manometric diagnosis spectrum.

Esophagogastric junction morphology and contractile integral on high-resolution manometry in asymptomatic healthy volunteers: An international multicenter study.

BACKGROUND: Esophagogastric junction contractile integral (EGJ-CI) and EGJ morphology are high-resolution manometry (HRM) metrics that assess EGJ barrier function. Normative data standardized across world regions and HRM manufacturers are limited. METHODS: Our aim was to determine normative EGJ metrics in a large international cohort of healthy volunteers undergoing HRM (Medtronic, Laborie, and Diversatek software) acquired from 16 countries in four world regions. EGJ-CI was calculated by the same two investigators using a distal contractile integral-like measurement across the EGJ for three respiratory cycles and corrected for respiration (mm Hg cm), using manufacturer-specific software tools. EGJ morphology was designated according to Chicago Classification v3.0. Median EGJ-CI values were calculated across age, genders, HRM systems, and regions. RESULTS: Of 484 studies (28.0 years, 56.2% F, 60.7% Medtronic studies, 26.0% Laborie, and 13.2% Diversatek), EGJ morphology was type 1 in 97.1%. Median EGJ-CI was similar between Medtronic (37.0 mm Hg cm, IQR 23.6-53.7 mm Hg cm) and Diversatek (34.9 mm Hg cm, IQR 22.1-56.1 mm Hg cm, P = 0.87), but was significantly higher using Laborie equipment (56.5 mm Hg cm, IQR 35.0-75.3 mm Hg cm, P < 0.001). 5th percentile EGJ-CI values ranged from 6.9 to 12.1 mm Hg cm. EGJ-CI values were consistent across world regions, but different between manufacturers even within the same world region (P ≤ 0.001). Within Medtronic studies, EGJ-CI and basal LESP were similar in younger and older individuals (P ≥ 0.3) but higher in women (P < 0.001). CONCLUSIONS: EGJ morphology is predominantly type 1 in healthy adults. EGJ-CI varies widely in health, with significant gender influence, but is consistent within each HRM system. Manufacturer-specific normative values should be utilized for clinical HRM interpretation.

Chronic constipation in adults: Contemporary perspectives and clinical challenges. 1: Epidemiology, diagnosis, clinical associations, pathophysiology and investigation.

BACKGROUND: Chronic constipation is a prevalent disorder that affects patients' quality of life and consumes resources in healthcare systems worldwide. In clinical practice, it is still considered a challenge as clinicians frequently are unsure as to which treatments to use and when. Over a decade ago, a Neurogastroenterology & Motility journal supplement devoted to the investigation and management of constipation was published (2009; 21 (Suppl.2)). This included seven articles, disseminating all themes covered during a preceding 2-day meeting held in London, entitled "Current perspectives in chronic constipation: a scientific and clinical symposium." In October 2018, the 3rd London Masterclass, entitled "Contemporary management of constipation" was held, again over 2 days. All faculty members were invited to author two new review articles, which represent a collective synthesis of talks presented and discussions held during this meeting. PURPOSE: This article represents the first of these reviews, addressing epidemiology, diagnosis, clinical associations, pathophysiology, and investigation. Clearly, not all aspects of the condition can be covered in adequate detail; hence, there is a focus on particular "hot topics" and themes that are of contemporary interest. The second review addresses management of chronic constipation, covering behavioral, conservative, medical, and surgical therapies.