High-Resolution Manometry Thresholds and Motor Patterns Among Asymptomatic Individuals.

OBJECTIVE: High-resolution manometry (HRM) is the current standard for characterization of esophageal body and esophagogastric junction (EGJ) function. We aimed to examine the prevalence of abnormal esophageal motor patterns in health, and to determine optimal thresholds for software metrics across HRM systems. DESIGN: Manometry studies from asymptomatic adults were solicited from motility centers worldwide, and were manually analyzed using integrated relaxation pressure (IRP), distal latency (DL), and distal contractile integral (DCI) in standardized fashion. Normative thresholds were assessed using fifth and/or 95th percentile values. Chicago Classification v3.0 criteria were applied to determine motor patterns across HRM systems, study positions (upright vs supine), ages, and genders. RESULTS: Of 469 unique HRM studies (median age 28.0, range 18-79 years). 74.6% had a normal HRM pattern; none had achalasia. Ineffective esophageal motility (IEM) was the most frequent motor pattern identified (15.1% overall), followed by EGJ outflow obstruction (5.3%). Proportions with IEM were lower using stringent criteria (10.0%), especially in supine studies (7.1%-8.5%). Other motor patterns were rare (0.2%-4.1% overall) and did not vary by age or gender. DL thresholds were close to current norms across HRM systems, while IRP thresholds varied by HRM system and study position. Both fifth and 95th percentile DCI values were lower than current thresholds, both in upright and supine positions. CONCLUSIONS: Motor abnormalities are infrequent in healthy individuals and consist mainly of IEM, proportions of which are lower when using stringent criteria in the supine position. Thresholds for HRM metrics vary by HRM system and study position.

Breaks in peristaltic integrity predict abnormal esophageal bolus clearance better than contraction vigor or residual pressure at the esophagogastric junction.

BACKGROUND: High-resolution impedance manometry (HRIM) evaluates esophageal peristalsis and bolus transit. We used esophageal impedance integral (EII), the ratio between bolus presence before and after an expected peristaltic wave, to evaluate predictors of bolus transit. METHODS: From HRIM studies performed on 61 healthy volunteers (median age 27 years, 48%F), standard metrics were extracted from each of 10 supine water swallows: distal contractile integral (DCI, mmHg cm s), integrated relaxation pressure (IRP, mmHg), and breaks in peristaltic integrity (cm, using 20 mmHg isobaric contour). Pressure and impedance coordinates for each swallow were exported into a dedicated, python-based program for EII calculation (EII ratio ≥ 0.3 = abnormal bolus clearance). Univariate and multivariate analyses were performed to assess predictors of abnormal bolus clearance. KEY RESULTS: Of 591 swallows, 80.9% were intact, 10.5% were weak, and 8.6% failed. Visual analysis overestimated abnormal bolus clearance compared to EII ratio (p ≤ 0.01). Bolus clearance was complete (median EII ratio 0.0, IQR 0-0.12) in 82.0% of intact swallows in contrast to 53.3% of weak swallows (EII ratio 0.29, IQR 0.0-0.57), and 19.6% of failed swallows (EII ratio 0.5, IQR 0.34-0.73, p < 0.001). EII correlated best with break length (ρ = 0.52, p < 0.001), compared to IRP (ρ: -0.17) or DCI (ρ: -0.42). On ROC analysis, breaks predicted abnormal bolus transit better than DCI or IRP (AUC 0.79 vs. 0.25 vs. 0.44, p ≤ 0.03 for each). On logistic regression, breaks remained independently predictive of abnormal bolus transit (p < 0.001). CONCLUSIONS & INFERENCES: Breaks in peristaltic integrity predict abnormal bolus clearance better than DCI or IRP in healthy asymptomatic subjects.

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.

Validation and psychometric evaluation of the Spanish version of Brief Esophageal Dysphagia Questionnaire (BEDQ): Results of a multicentric study.

BACKGROUND: The recently developed Brief Esophageal Dysphagia Questionnaire (BEDQ) evaluates esophageal obstructive symptoms. Its initial evaluation showed strong psychometric properties. The aims of this study were to (a) translate and validate an international Spanish version of BEDQ and (b) evaluate its psychometric properties in a large Hispano-American sample of symptomatic individuals. METHODS: A Spanish BEDQ version was performed by Hispano-American experts using a Delphi process and reverse translation. Patients were prospectively recruited from seven centers in Spain and Latin America among individuals referred for high-resolution manometry (HRM). Patients completed several scores: Hospital Anxiety & Depression Scale (HADS), Eckardt score (ES), Gastroesophageal Reflux Questionnaire (GERDQ), and the BEDQ. Standardized psychometric analyses were performed. KEY RESULTS: A total of 426 patients were recruited. Spanish BEDQ showed excellent reliability (Cronbach's alpha = 0.91). Factor analysis confirmed its unidimensional character. Moderate significant correlations between BEDQ and other symptomatic scores were found, suggesting sufficient convergent validity. Patients with abnormal or obstructive HRM findings scored significantly higher when compared to normal or non-obstructive findings, respectively. Using a cutoff of 10, BEDQ showed a sensitivity of 65.38% and a specificity of 66.21% and an area under the curve of 0.71 for obstructive or major manometric diagnosis. CONCLUSIONS AND INFERENCES: A widely usable Spanish BEDQ version has been validated. We confirm its excellent psychometric properties in our patients, confirming the appropriateness of its use in different populations.

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.

Normal values and regional differences in oesophageal impedance-pH metrics: a consensus analysis of impedance-pH studies from around the world.

OBJECTIVE: Limitations of existing impedance-pH thresholds include small sample size of normative studies, inclusion of artefactual pH drops and incorrect identification of impedance reflux events. We aimed to obtain new impedance-pH thresholds from expert consensus analysis of tracings from a large number of healthy subjects. DESIGN: Of 541 studies performed worldwide using two different systems (Diversatek, USA, and Laborie, Netherlands), 150 tracings with oesophageal diagnoses, behavioural disorders and study-related artefacts were excluded. The remainder studies were subject to two reviewer consensus analysis, in-person or through video conference, consisting of editing meals and pH drops, identification of impedance reflux and postreflux swallow-induced peristaltic wave (PSPW) using strict pre-established criteria and measurement of distal mean nocturnal baseline impedance (MNBI). RESULTS: Consensus analysis was performed in 391 tracings (age 32.7 years, range 18-71, 54.2% female). Normative thresholds were significantly different between Diversatek and Laborie (total acid exposure time: 2.8% and 5%; reflux episodes: 55 and 78; MNBI at 3 cm: 1400 and 1500 ohms, at 5 cm: 1400 and 1800 ohms). Males had higher acid exposure, more reflux episodes and lower MNBI. Significant regional differences were identified, including higher PSPW scores in Western countries, and higher MNBI in Asia using Diversatek, and higher acid exposure in the Netherlands, higher MNBI in Asia and South Africa, and lower MNBI in Turkey using Laborie. CONCLUSION: Normal impedance-pH monitoring thresholds have regional and system-related differences. Clinical interpretation needs to use normal thresholds valid for the system used and world region, following careful editing of the tracings.

Recommendations of the Spanish Association of Neurogastroenterology and Motility (ASENEM) to restart the activity of gastrintestinal motility laboratories after the state of alarm called due to the Covid-19 pandemic. / Recomendaciones de la Asociación Española de Neurogastroenterología y Motilidad (ASENEM) para el reinicio de la actividad de los laboratorios de motilidad digestiva, tras el confinamiento por el estado de alarma decretado a raíz de la pandemia por COVID-19.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was responsible for the outbreak of the 2019 coronavirus disease (COVID-19), which is now considered as a pandemic. The prevention strategies adopted have included social distancing measures and the modification, reduction or interruption of a large proportion of routine healthcare activity. This has had a significant impact on the care provided in Gastrointestinal Motility Units. Having passed the peak, in terms of mortality and infections, a gradual reduction in transmission figures has been observed in Spain and other European countries. The risk of reactivation, however, remains high, so it is necessary to have a plan in place that allows healthcare centres to safely resume, for their patients and professionals, instrumental examinations linked to the management of motor pathology. Based on the available scientific evidence and the consensus of a panel of experts, the Spanish Association of Neurogastroenterology and Motility (ASENEM) has drawn up a series of practical recommendations, which have been adapted to the risks inherent in each activity. These include individual protection proposals, as well as organisational and structural measures, which are conceived to allow for the gradual resumption of examinations while minimising the possibility of contagion.

Ineffective esophageal motility and bolus clearance. A study with combined high-resolution manometry and impedance in asymptomatic controls and patients.

BACKGROUND: The definition and relevance of ineffective esophageal motility (IEM) remains debated. Our aim was to determine motility patterns and symptoms associated with IEM defined as impaired bolus clearance. METHODS: To define altered bolus clearance, normal range of swallows with complete bolus transit (CBT) on high-resolution impedance manometry (HRIM) was determined in 44 asymptomatic controls. The results were then applied to a cohort of 81 patients with esophageal symptoms to determine the motility patterns which best predicted altered bolus clearance. Subsequently, in a cohort of 281 consecutive patients the identified motility patterns were compared with patients' customary symptoms. KEY RESULTS: In asymptomatic controls, the normal range of swallows with CBT was 50%-100%. In patients, altered bolus transit (<50% CBT) was only associated with 30% or more failed contractions (P < .001). Neither weak peristalsis nor absence of contraction reserve (CR) was associated with altered bolus clearance. The patterns which best predicted altered bolus clearance were failed contractions ≥30% (specificity 88.2% and sensitivity of 84.6%), and ≥70% ineffective (failed + weak) contractions (sensitivity 84.6% and specificity 80.9%). No motility pattern was correlated to symptom scores. CONCLUSIONS AND INFERENCES: Based on bolus clearance assessed by HRIM, ≥30% failed contractions and ≥70% ineffective contractions have the best sensitivity and specificity to predict altered bolus clearance. Weak contractions and absence of CR are not relevant with respect to bolus clearance.

Fair reliability of eckardt scores in achalasia and non-achalasia patients: Psychometric properties of the eckardt spanish version in a multicentric study.

BACKGROUND: Eckardt symptom score (ESS) is the most used tool for the evaluation of esophageal symptoms. Recent data suggest that it might have suboptimal reliability and validity. The aims of this study were as follows: (a) Develop and validate an international Spanish ESS version. (b) Perform psychometric ESS evaluation in patients with achalasia and non-achalasia patients. METHODS: Eckardt symptom score translation was performed by Delphi process. ESS psychometric evaluation was done in two different samples of patients referred for manometry. First sample: 430 dysphagia non-achalasia patients. Second sample: 161 achalasia patients. Internal consistency was evaluated using Cronbach's α and Guttman coefficient (<0.5 = unacceptable. 0.5-0.7 = fair. >0.7 = acceptable). KEY RESULTS: Our data show that in patients without and with achalasia, ESS behaves similarly. Both show a fair reliability with Cronbach's α of 0.57 and 0.65, respectively. Based on our results, we recommend interpretation of the Spanish ESS be done with caution. The psychometric quality of the ESS could not be improved by removal of any items based on the single-factor structure of the scale and no items meeting criteria for elimination. CONCLUSIONS AND INFERENCES: Eckardt symptom score Spanish translation was developed. ESS showed a fair reliability for the evaluation of patients with any causes of dysphagia. Our results highlight the need for development and psychometric validation of new dysphagia scoring tools.

Genetic variation in the lymphotoxin-α (LTA)/tumour necrosis factor-α (TNFα) locus as a risk factor for idiopathic achalasia.

BACKGROUND: Idiopathic achalasia is a rare motor disorder of the oesophagus characterised by neuronal loss at the lower oesophageal sphincter. Achalasia is generally accepted as a multifactorial disorder with various genetic and environmental factors being risk-associated. Since genetic factors predisposing to achalasia have been poorly documented, we assessed whether single nucleotide polymorphisms (SNPs) in genes mediating immune response and neuronal function contribute to achalasia susceptibility. METHODS: 391 SNPs covering 190 immune and 67 neuronal genes were genotyped in an exploratory cohort from Central Europe (589 achalasia patients, 794 healthy volunteers (HVs)). 24 SNPs (p<0.05) were validated in an Italian (160 achalasia patients, 278 HVs) and Spanish cohort (281 achalasia patients, 296 HVs). 16 SNPs in linkage disequilibrium (LD) with rs1799724 (r(2)>0.2) were genotyped in the exploratory cohort. Genotype distributions of patients (1030) and HVs (1368) were compared using Cochran-Armitage trend test. RESULTS: The rs1799724 SNP located between the lymphotoxin-α (LTA) and tumour necrosis factor-α (TNFα) genes was significantly associated with achalasia and withstood correction for testing multiple SNPs (p=1.17E-4, OR=1.41 (1.18 to 1.67)). SNPs in high LD with rs1799724 were associated with achalasia. Three SNPs located in myosin-5B, adrenergic receptor-ß-2 and interleukin-13 (IL13) showed nominally significant association to achalasia that was strengthened by replication. CONCLUSIONS: Our study provides evidence for rs1799724 at the LTA/TNFα locus as a susceptibility factor for idiopathic achalasia. Additional studies are needed to dissect which genetic variants in the LTA/TNFα locus are disease-causing and confirm other variants as potential susceptibility factors for achalasia.

Enterohepatic Helicobacter other than Helicobacter pylori.

The Helicobacter genus includes Gram negative bacteria which were originally considered to belong to the Campylobacter genus. They have been classified in a separate genus since 1989 because they have different biochemical characteristics, with more than 24 species having been identified and more still being studied.H. pylori is the best known. It has an important etiopathogenic role in peptic ulcer disease and gastric cancer. Enterohepatic Helicobacters (EHH) other than H. pylori colonize the bowel, biliary tree and liver of animals and human beings with pathogenic potential. The difficulties existing to correctly isolate these microorganisms limit the description of their true prevalence and of the diseases they cause. Many studies have tried to discover the different clinical implications of EHH. Diseases like chronic liver disease, autoimmune hepatitis, hepatocarcinoma, autoimmune hepatobiliary disease, biliary lithiasis, cholangiocarcinoma and gallbladder cancer, Meckel´s diverticulum, acute appendicitis and inflammatory bowel disease have been related with different EHH species with different results, although their prevalence is greater than in healthy subjects. However, these data are currently not sufficient to draw definitive conclusions. Finally, the best known role of EHH in bowel disease is production of acute and chronic diarrhea pictures initially referred to as Campylobacter. H. pullorum has been identified in patients with acute gastroenteritis. The correct identification of EHH as producers of infectious gastroenteritis is found in its antibiotic susceptibility. It is generally macrolide-susceptible and quinolone-resistant.

Myenteric antiplexus antibodies and class II HLA in achalasia.

Achalasia, a motor disorder of the esophagus, is accompanied by autoimmune phenomena that could be playing a role in the pathogenesis of the disease. Our objective was to establish the genotypic frequency of the HLA-DR and DQ alleles in patients with achalasia and to establish their relationship with the presence of myenteric antiplexus antibodies in our geographic area. A total of 92 patients diagnosed with achalasia and two control groups with 275 healthy subjects were studied for HLA typing and 40 for autoantibodies determination. The myenteric antiplexus antibodies were positive in 50 patients (54.3%) and in 3 healthy subjects (7.5%) (P < 0.001). The patients showed a significantly higher frequency of DQA1*0103 and DQB1*0603 than was found in the controls. The heterodimer DQA1*0103-DQB1*0603 was increased in the patients [odds ratio (OR) = 2.57]. In regard to the association between the HLA DQA1 and DQB1 alleles and the antiplexus antibodies, these antibodies were found in greater prevalence in those patients with the DQA1*0103 and DQB1*0603 alleles, and the differences were statistically significant (OR = 3.17 and OR = 5.82, respectively). All of the women and 66.7% of the men with achalasia and the DQB1*0603 allele or the DQA1*0103-DQB1*0603 heterodimer were positive for antibodies.