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Objectives: High‐resolution manometry (HRM) and esophagography are used for achalasia diagnosis; however, achalasia phenotypes combining esophageal motility and morphology are unknown. Moreover, predicting treatment outcomes of peroral endoscopic myotomy (POEM) in treatment‐naïve patients remains an unmet need. Methods: In this multicenter cohort study, we included 1824 treatment‐naïve patients diagnosed with achalasia. In total, 1778 patients underwent POEM. Clustering by machine learning was conducted to identify achalasia phenotypes using patients' demographic data, including age, sex, disease duration, body mass index, and HRM/esophagography findings. Machine learning models were developed to predict persistent symptoms (Eckardt score ≥3) and reflux esophagitis (RE) (Los Angeles grades A–D) after POEM. Results: Machine learning identified three achalasia phenotypes: phenotype 1, type I achalasia with a dilated esophagus (n = 676; 37.0%); phenotype 2, type II achalasia with a dilated esophagus (n = 203; 11.1%); and phenotype 3, late‐onset type I–III achalasia with a nondilated esophagus (n = 619, 33.9%). Types I and II achalasia in phenotypes 1 and 2 exhibited different clinical characteristics from those in phenotype 3, implying different pathophysiologies within the same HRM diagnosis. A predictive model for persistent symptoms exhibited an area under the curve of 0.70. Pre‐POEM Eckardt score ≥6 was the greatest contributing factor for persistent symptoms. The area under the curve for post‐POEM RE was 0.61. Conclusion: Achalasia phenotypes combining esophageal motility and morphology indicated multiple disease pathophysiologies. Machine learning helped develop an optimal risk stratification model for persistent symptoms with novel insights into treatment resistance factors. [ABSTRACT FROM AUTHOR]

Background and Aim: Nonsteroidal anti‐inflammatory drugs (NSAIDs) damage the small intestine via neutrophil infiltration driven by the mucosal invasion of enterobacteria. The antimicrobial function of neutrophils is partially dependent on neutrophil extracellular traps (NETs). Excessive NET formation has been associated with several inflammatory diseases. Here, we aimed to investigate the role of NETs in NSAID‐induced small intestinal damage using human samples and an experimental mouse model. Methods: Human small intestine specimens were obtained from NSAID users during double‐balloon enteroscopy. Wild‐type, protein arginine deiminase 4 (PAD4) knockout, and antibiotic‐treated mice were administered indomethacin to induce small intestinal injury. The expression of NET‐associated proteins, including PAD4, citrullinated histone H3 (CitH3), cell‐free DNA, and myeloperoxidase (MPO), was evaluated. Results: The double‐positive stained area with CitH3 and MPO, which is specific for neutrophil‐derived extracellular traps, was significantly high in the injured small intestinal mucosa of NSAID users. In a mouse model, small intestinal damage developed at 6 h after indomethacin administration, accompanied by increased mRNA levels of interleukin‐1β and keratinocyte chemoattractant and elevated NET‐associated protein levels of PAD4, CitH3, and MPO in small intestine and serum levels of cell‐free DNA. Both genetic deletion and pharmacological inhibition of PAD4 attenuated this damage by reducing the mRNA expression of inflammatory cytokines and NET‐associated proteins. Furthermore, mice pretreated with antibiotics showed resistance to indomethacin‐induced small intestinal damage, with less NET formation. Conclusion: These results suggest that NETs aggravate NSAID‐induced small intestinal injury. Therefore, NET inhibition could be a potential treatment for NSAID‐induced small intestinal injury. [ABSTRACT FROM AUTHOR]

Introduction. An on-going coronavirus disease 2019 (COVID-19) has become a challenge all over the world. Since an endoscopy unit and its staff are at potentially high risk for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, we conducted a survey for the management of the gastrointestinal endoscopic practice, personal protective equipment (PPE), and risk assessment for COVID-19 during the pandemic at multiple facilities.

Summary: Background: Mechanisms underlying perception of dysphagia and chest pain have not been completely elucidated, although oesophageal mucosal afferent nerves might play an important role. Aims: To evaluate the relationship between oesophageal mucosal afferent nerves and the severity of dysphagia and chest pain in oesophageal motility disorders. Methods: We prospectively recruited patients with oesophageal motility disorders having dysphagia and/or chest pain from whom oesophageal biopsies were obtained. High‐resolution manometry classified patients into disorders of oesophagogastric junction (OGJ) outflow and disorders of peristalsis. Symptom severity was assessed using validated questionnaires including Brief Oesophageal Dysphagia Questionnaire (BEDQ). Immunohistochemistry was performed on oesophageal biopsies to evaluate the location of calcitonin gene‐related peptide (CGRP)‐immunoreactive mucosal afferent nerves. Findings were compared to existing data from 10 asymptomatic healthy volunteers. Results: Of 79 patients, 61 patients had disorders of OGJ outflow and 18 had disorders of peristalsis. CGRP‐immunoreactive mucosal nerves were more superficially located in the mucosa of patients with oesophageal motility disorders compared to healthy volunteers. Within disorders of OGJ outflow, the location of CGRP‐immunoreactive nerves negatively correlated with BEDQ score both in the proximal (ρ = −0.567, p < 0.001) and distal oesophagus (ρ = −0.396, p = 0.003). In the proximal oesophagus, strong chest pain was associated with more superficially located mucosal nerves than weak chest pain (p = 0.04). Multivariate analysis showed superficial nerves in the proximal oesophagus was independently associated with severe dysphagia in disorders of OGJ outflow (p = 0.008). Conclusions: Superficial location of mucosal nerves in the proximal oesophagus might contribute to symptoms, especially severe dysphagia, in disorders of OGJ outflow. [ABSTRACT FROM AUTHOR]

Background and Aim: Mental status such as anxiety and depression in patients with non‐esophageal eosinophilic gastrointestinal diseases (non‐EoE EGIDs) has not been studied. The aim of this study was to evaluate whether patients with non‐EoE EGIDs had mental disorders and decreased mental‐health‐related quality of life (QOL) similar to those in patients with disorders of gut–brain interaction (DGBI). Methods: We enrolled patients with non‐EoE EGIDs and DGBI visiting the Osaka Metropolitan University Hospital, and the measures listed below were compared between the groups. We collected data using the following questionnaires: hospital anxiety and depression scale, and short form (SF)‐8 including mental component summary (MCS)‐8. Results: We evaluated 21 and 17 patients with non‐EoE EGIDs and DGBI, respectively. The anxiety score was not significantly different between the groups. The proportion of patients with possible anxiety was not significantly different between the groups (19.0% vs 33.3%). These results show that patients with non‐EoE EGIDs had anxiety that might be equivalent to that of patients with DGBI. The depression score and proportion of patients with possible depression in the non‐EoE EGID group tended to be lower than those in the DGBI group. MCS‐8 scores were not significantly different between the non‐EoE EGID and DGBI groups, which might imply an equivalent decrease in mental‐health‐related QOL in both groups of patients. In patients with non‐EoE EGIDs, the anxiety score had a significant inverse association with the MCS‐8 score. Conclusions: Patients with non‐EoE EGIDs may have anxiety that correlates with decreased mental‐health‐related QOL. [ABSTRACT FROM AUTHOR]

Eosinophilic esophagitis (EoE) is predominantly found in middle-aged men among adults. There are few reports about EoE in the elderly, despite an ageing population. The study aimed to define the prevalence and clinical characteristics of EoE amongst older adults. Elderly patients (defined as those ≥65 years) were compared to younger adults (18–64) in terms of clinical characteristics (age, gender, presenting symptoms, comorbidities), histological activity (eosinophil count), treatment modality and response to treatment. A pre- existing prospectively generated database of all EoE patients presenting to our department between February 2010 and December 2022 was interrogated. 309 patients who underwent endoscopy and esophageal biopsy and were found to have ≥15 eosinophils/HPF were defined as having EoE and were included for study. Statistical analyses were performed using Fisher's extract test or Mann–Whitney U test. 309 cases of EoE were recorded, mean age 45.7, range (21–88 years), of which20 patients were aged 65 years and over. Compared to younger patients, those aged ≥65 had more medical comorbidities (15 [75%] vs 111[38%], p = 0.002), and instead a non-significant trend toward less fibrosis (0.25 vs 0.46, p = 0.117). Although rate of cases required topical steroid (TCS) therapy was similar, none received repeated or maintenance TCS therapy in elderly. In our cohort, only 20 patients (6%) were aged 65 years or older, suggesting that EoE is uncommon in the elderly. The clinical characteristics of EoE in the older age group were similar to the younger patients. Future studies with prospective data collection may determine if EoE disappears with age, or if the younger mean age is reflective of an increasing prevalence in recent years, that may be realized in the elderly EoE population in the future. [ABSTRACT FROM AUTHOR]

Background and Aim: Absent contractility (AC) and ineffective esophageal motility (IEM) are esophageal hypomotility disorders diagnosed using high‐resolution manometry (HRM). Patient characteristics and disease course of these conditions and differential diagnosis between AC and achalasia are yet to be elucidated. Methods: A multicenter study involving 10 high‐volume hospitals was conducted. Starlet HRM findings were compared between AC and achalasia. Patient characteristics including underlying disorders and disease courses were analyzed in AC and IEM. Results: Fifty‐three patients with AC and 92 with IEM were diagnosed, while achalasia was diagnosed in 1784 patients using the Chicago classification v3.0 (CCv3.0). The cut‐off integrated relaxation pressure (IRP) value at 15.7 mmHg showed maximum sensitivity (0.80) and specificity (0.87) for differential diagnosis of AC from type I achalasia. While most ACs were based on systemic disorders such as scleroderma (34%) and neuromuscular diseases (8%), 23% were sporadic cases. The symptom severity of AC was not higher than that of IEM. Regarding the diagnosis of IEM, the more stringent CCv4.0 excluded 14.1% of IEM patients than the CCv3.0, although patient characteristics did not change. In patients with the hypomotile esophagus, concomitance of reflux esophagitis was associated with low distal contractile integral and IRP values. AC and IEM transferred between each other, paralleling with the underlying disease course, although no transition to achalasia was observed. Conclusion: A successful determination of the optimal cut‐off IRP value was achieved using the starlet HRM system to differentiate AC and achalasia. Follow‐up HRM is also useful for differentiating AC from achalasia. Symptom severity may depend on underlying diseases instead of hypomotility severity. [ABSTRACT FROM AUTHOR]