Neutrophil extracellular trap formation and its implications in nonsteroidal anti-inflammatory drug-induced small intestinal injury.

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-1ß 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.

Esophageal submucosal hematoma during transnasal endoscopy: A rare case report.

Esophageal submucosal hematoma is a rare, often incidental complication of therapeutic endoscopic procedures marked by disrupted blood vessels beneath the esophageal mucosa, forming a hematoma. We report the unique case of a severely thin and alcoholic 38-year-old woman with a history of reflux esophagitis who developed an esophageal submucosal hematoma during an unsedated transnasal endoscopy for health check-up. During the procedure, the patient experienced strong vomiting reflexes and vomited blood, leading to the initial suspicion of either Mallory-Weiss syndrome or epistaxis. However, subsequent sedated endoscopy revealed an esophageal submucosal tumor-like lesion and a mucosal laceration with blood clots, prompting a dual diagnosis of esophageal submucosal hematoma and Mallory-Weiss syndrome. The bleeding was not severe enough to require hemostatic intervention. The patient opted for conservative treatment with vonoprazan, which resulted in the improvement and healing of the hematoma within 28 days. This is the first report of an esophageal submucosal hematoma during transnasal endoscopy and emphasizes the importance of including an esophageal submucosal hematoma and Mallory-Weiss syndrome in the differential diagnosis of hematemesis encountered in similar scenarios. Factors such as severe thinness, daily alcohol consumption, and reflux esophagitis may have possibly contributed to the development of the esophageal submucosal hematoma in this patient.

Correlation between anxiety and decreased quality of life in patients with non-esophageal eosinophilic gastrointestinal diseases.

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.

Responses of Proton Pump Inhibitors and Potassium-Competitive Acid Blockers According to Outcomes of Symptom, Endoscopy, and Histology in Patients With Eosinophilic Esophagitis.

GOALS: We aimed to examine the response rate to proton pump inhibitors (PPIs) and potassium-competitive acid blockers and the prevalence of topical corticosteroid (TCS) therapy as the second-line treatment for eosinophilic esophagitis (EoE). BACKGROUND: Acid-suppressive drugs such as PPIs and potassium-competitive acid blockers are often used to treat EoE. Treatment response is based on outcomes including symptoms, endoscopy, and histology; however, the detailed response rate to PPI/P-CAB is unknown. STUDY: In total, 236 patients with histologically confirmed EoE who received PPI/P-CAB as the first-line treatment were included. We assessed the symptoms, endoscopic reference score (EREFS), and histology [eosinophils per high-power field (eos/hpf)] 8 weeks after PPI/P-CAB administration. Complete normalization was defined as the disappearance of symptoms, EREFS score 0, or 0-1 eos/hpf, and response as disappearance or improvement of symptoms, EREFS score ≤2, or <15 eos/hpf. The prevalence of TCS therapy in each response group was assessed. RESULTS: Complete normalization was achieved in 25%, 50%, 36%, and 8% of patients for symptoms, endoscopy, histology, and all 3 outcomes, respectively. The response rates were 81%, 87%, 87%, 75%, and 60% for symptoms, endoscopy, histology, and all 3 outcomes, respectively. TCS use was significantly lower (8%) in patients who achieved response of all 3 outcomes than in other groups and was dependent on the number of outcomes with nonresponse. CONCLUSIONS: Complete normalization of symptoms, endoscopy, and histology using PPI/P-CAB is uncommon. Based on treatment efficacy by response/nonresponse, TCS was the secondary treatment in cases with an increase in the number of nonresponse outcomes.

Superficial oesophageal mucosal innervation may contribute to severity of symptoms in oesophageal motility disorders.

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.

Association of direct oral anticoagulant and delayed bleeding with pharmacokinetics after endoscopic submucosal dissection.

BACKGROUND AND AIMS: Pharmacokinetic parameters, such as drug plasma level at trough, time to maximum plasma concentration (Tmax), and coagulation factor Xa (FXa) activity generally predict factors for the anticoagulant effects of direct oral anticoagulants (DOACs). Although GI bleeding is a major adverse event after endoscopic submucosal dissection (ESD), little is known about the association between post-ESD bleeding in patients taking DOACs and the pharmacologic parameters. This study aimed to evaluate pharmacologic risk factors for post-ESD bleeding in patients taking DOACs. METHODS: We prospectively evaluated the incidence of post-ESD bleeding in patients taking DOACs between April 2018 and May 2022 at 21 Japanese institutions and investigated the association with post-ESD bleeding and pharmacologic factors, including plasma concentration and FXa activity at trough and Tmax. RESULTS: The incidence of post-ESD bleeding was 12.8% (14 of 109; 95% confidence interval [CI], 7.2-20.6). Although plasma DOAC concentration and plasma level/dose ratio at trough and Tmax varied widely among individuals, a significant correlation with plasma concentration and FXa activity was observed (apixaban: correlation coefficient, -0.893; P < .001). On multivariate analysis, risk factors for post-ESD bleeding in patients taking DOACs were higher age (odds ratio [OR], 1.192; 95% CI, 1.020-1.392; P = .027) and high anticoagulant ability analyzed by FXa activity at trough and Tmax (OR, 6.056; 95% CI, 1.094-33.529; P = .039). CONCLUSIONS: The incidence of post-ESD bleeding in patients taking DOACs was high, especially in older patients and with high anticoagulant effects of DOACs. Measurement of pharmacokinetic parameters of DOACs may be useful in identifying patients at higher risk of post-ESD bleeding.

The impact of COVID-19 on Japanese patients with eosinophilic gastrointestinal disorders during the vaccination era.

Background: Eosinophilic gastrointestinal disorders (EGIDs) are chronic allergic diseases categorized as eosinophilic esophagitis (EoE) and non-EoE EGIDs. Few studies regarding the association between EGIDs and coronavirus disease 2019 (COVID-19) have been reported. Although most Japanese individuals received the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine, the incidence of COVID-19 remained high in 2022. This study examines the incidence of COVID-19 in patients with EGIDs during the vaccination era. Methods: Patients with EGIDs who visited our department between October and December 2022 were enrolled in the study. The incidence and severity of COVID-19 prior to October 1, 2022 were determined. Patients who reported having COVID-19 also reported their hospitalization history, intensive care unit admissions, and EGID flares. The number of SARS-CoV-2 vaccinations received and treatment for EGIDs were obtained from the patients' medical records. Results: Of 111 patients with EGIDs (65 with EoE and 46 with non-EoE EGIDs) included in this study, 31 (28%) patients reported having COVID-19, including 14 (22%) with EoE and 17 (37%) with non-EoE EGIDs. Fifty-nine (84%) patients received two or more vaccinations, and 11 (16%) patients received no vaccinations. COVID-19 was mild in all but one patient who had moderate symptoms. COVID-19 was not associated with EGID flares. EGID treatments and an unvaccinated status were not associated with an increased risk of COVID-19. Conclusion: COVID-19 was mild in patients with EGIDs and not associated with EGIDs flares during the vaccination era. There was a relatively high incidence of COVID-19 among patients with non-EoE EGIDs.

Achalasia phenotypes and prediction of peroral endoscopic myotomy outcomes using machine learning.

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.

Impact of the COVID-19 Pandemic on the Lifestyle and Psychosocial Behavior of Patients with Inflammatory Bowel Diseases: A Narrative Review.

The coronavirus disease (COVID-19) pandemic has had a considerable impact on the global healthcare system and potentially the clinical course of patients with inflammatory bowel disease (IBD). Although IBD is a chronic disease, its therapy (except steroid therapy) does not increase the risk of contracting or aggravating COVID-19. However, the clinical course of patients is significantly influenced by environmental factors. Social restrictions due to the pandemic or the fear of contracting the virus have influenced lifestyle and psychosocial behaviors that may worsen the clinical course of patients with IBD. This narrative literature review summarizes the current evidence on the impact of the COVID-19 pandemic on the lifestyle and psychosocial behaviors of patients with IBD. The COVID-19 pandemic negatively affected the lifestyle and psychosocial behaviors of patients with IBD. Furthermore, patients with IBD failed to maintain medication adherence, thus affecting the clinical course of their condition.

Prevalence of elderly eosinophilic esophagitis and their clinical characteristics.

BACKGROUND AND AIMS: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Clinical characteristics of absent contractility and ineffective esophageal motility: a multicenter study in Japan.

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.

Risk factors for adverse events associated with endoscopic submucosal dissection for superficial pharyngeal cancer.

BACKGROUND: Superficial pharyngeal cancer can be treated with curative intent while preserving function using minimally invasive peroral endoscopic resection techniques such as endoscopic submucosal dissection (ESD). However, severe adverse events occasionally occur, such as laryngeal edema requiring temporary tracheotomy and fistula formation. Therefore, we investigated the risk factors for adverse events associated with ESD for superficial pharyngeal cancer. METHODS: This retrospective observational study was conducted at a single institution, and 63 patients who underwent ESD were enrolled. The primary outcome was the risk factors for adverse events associated with ESD. The secondary outcomes were adverse events associated with ESD and their frequency. RESULTS: The overall adverse event rate was 15.9% (10/63). The incidence of laryngeal edema requiring prophylactic temporary tracheotomy was 11.1%, while laryngeal edema requiring emergency temporary tracheotomy, postoperative bleeding, aspiration pneumonia, fistula, abscess, and stricture formation occurred in 1.6% of patients, respectively. Logistic regression analyses showed that a history of radiotherapy for head and neck cancer was a risk factor for adverse events (odds ratio [OR], 16.67; 95% confidence interval [CI], 3.04-91.34; p = 0.001). After adjusting the model for differences in the baseline risk factors using the inverse probability of treatment weighting method, the adverse events were found to increase in association with a history of radiotherapy for head and neck cancer (OR, 39.66; 95% CI,5.85-268.72; p < 0.001). CONCLUSION: History of radiotherapy for head and neck cancer is an independent risk factor for adverse events associated with ESD for superficial pharyngeal cancer. Among adverse events, laryngeal edema requiring prophylactic temporary tracheotomy was particularly high.

Upper gastrointestinal endoscopic findings in functional constipation and irritable bowel syndrome diagnosed using the Rome IV criteria: a cross-sectional survey during a medical check-up in Japan.

BACKGROUND: The Rome IV criteria have been established as an international standard for diagnosing disorders of gut-brain interaction. In this study, we aimed to examine the upper gastrointestinal (GI) endoscopic findings and symptoms of subjects with functional constipation (FC) and irritable bowel syndrome (IBS) of individuals undergoing a medical check-up. METHODS: A total of 13,729 subjects underwent a medical check-up at Osaka City University-affiliated clinic, MedCity21, between April 2018 and March 2019. Among the 5,840 subjects who underwent screening upper GI endoscopy and completed a questionnaire based on the Rome IV criteria, 5,402 subjects were consecutively enrolled after excluding subjects with a large amount of gastric residue (n = 6), those who had previously undergone partial or total gastrectomy (n = 40), or those with daily use of low-dose aspirin (n = 82), nonsteroidal anti-inflammatory drugs (n = 63), or acid secretion inhibitors (n = 308). RESULTS: Robust Poisson regression analyses adjusted for age, sex, Helicobacter pylori infection status, alcohol intake, and smoking habits showed a significant association between FC and corpus erosion (adjusted prevalence ratio [aPR], 2.93; 95% confidence interval [CI], 1.51-5.67; p < 0.01) and red streaks (aPR, 3.83; 95% CI, 2.53-5.79; p < 0.01), whereas IBS was significantly associated with erosive gastritis (aPR, 8.46; 95% CI, 4.89-14.67; p < 0.01) and duodenitis (aPR, 7.28; 95% CI, 3.64-14.59; p < 0.01). Red streaks tended to be associated with IBS (aPR, 1.96; 95% CI, 1.00-3.83; p = 0.05). Subjects with IBS were the most to complain of both upper and lower GI symptoms and psychological symptoms, followed by those with FC and controls. IBS subjects with erosive gastritis or duodenitis had significantly more complaints of stomachache and feeling stressed than those without erosive gastritis or duodenitis (54.5% vs. 18.8%; p = 0.03 and 66.7% vs. 25.0%; p = 0.01). CONCLUSIONS: Subjects with FC and IBS had a variety of upper GI and psychological symptoms. In the upper GI endoscopic findings, corpus erosion and red streaks were associated with FC, and erosive gastritis, duodenitis, and possibly red streaks were associated with IBS.

Pretreatment serum monocyte chemoattractant protein-1 as a predictor of long-term outcome by ustekinumab in patients with Crohn's disease.

BACKGROUND AND AIMS: Ustekinumab has been proven to be effective for treatment of patients with Crohn's disease; however, 30-40% of patients have been reported to lose clinical response within 2 years. We aimed to evaluate the efficacy of ustekinumab and identify predictors of short-term and long-term efficacy in Crohn's disease. METHODS: Patients with Crohn's disease receiving their first ustekinumab infusion in our hospital between June 2017 and September 2020 were prospectively enrolled. Concentrations of serum cytokines and chemokines were measured using a multiplex bead array assay. RESULTS: Fifty-nine Crohn's disease patients were enrolled in this study. Among 34 clinically active patients, 38.2% achieved a clinical response at week 8. None of the assayed factors were associated with short-term clinical response. Cumulative persistence rates of ustekinumab were 77.6% at 1 year and 58.9% at 2 years. Univariate Cox regression analysis revealed that Harvey-Bradshaw Index scores at baseline, concomitant immunomodulator treatment, and concentrations of interferon gamma-induced protein-10, monocyte chemoattractant protein-1 (MCP-1), and interleukin (IL)-1RA, IL-4, IL-6, and IL-8 were significantly associated with loss of efficacy. Multivariate Cox regression analysis found that biologic naïve status (hazard ratio [HR]: 0.1191, 95% confidence interval [CI]: 0.02458-0.5774) and MCP-1 concentrations (HR: 1.038, 95% CI: 1.015-1.062) were significantly and associated with loss of sustained efficacy for ustekinumab treatment. CONCLUSIONS: Our findings suggest that pretreatment serum MCP-1 analysis, combined with a history of biologic use, could be a novel biomarker for predicting the long-term efficacy of ustekinumab in patients with Crohn's disease.

Neutrophil-to-lymphocyte ratio may predict clinical relapse in ulcerative colitis patients with mucosal healing.

Endoscopic mucosal healing (MH) is an important treatment goal for patients with ulcerative colitis (UC). The neutrophil-to-lymphocyte ratio (NLR) reflects systemic inflammation and has been reported to be a useful predictive marker for UC. This study aimed to evaluate the clinical utility of the NLR for predicting clinical relapse in UC patients with MH. We retrospectively enrolled patients with UC who underwent colonoscopy at the Osaka City University Hospital between January 2010 and December 2010, whose Mayo Endoscopic Subscore was 0 or 1. The correlation between the incidence of relapse and demographic factors, including the NLR, was analyzed. We included 129 patients in the present study. The median NLR at the time of endoscopy was 1.98, and differences in the high NLR group and the low NLR group were compared. During a median follow-up period of 46.4 months, 58 patients (45.0%) experienced relapse. The cumulative relapse-free rate was significantly higher in the low NLR group than in the high NLR group (P = 0.03, log-rank test). Multivariate analysis identified high NLR as an independent prognostic factor for clinical relapse (hazard ratio, 1.74; 95% confidence interval, 1.02-2.98; P = 0.04). NLR is a novel and useful predictor of clinical relapse in UC patients with MH, and it can potentially be a strong indicator to determine the appropriate treatment strategy and decision-making in clinical practice.

Impact of peroral endoscopic myotomy on high-resolution manometry findings and their association with the procedure's outcomes.

BACKGROUND AND AIMS: Peroral endoscopic myotomy (POEM) is conducted for patients with esophageal motility disorders based on high-resolution manometry (HRM) findings. However, the impact of POEM on HRM findings and the associations between post-POEM HRM and outcomes have not been clarified. METHODS: In a multicenter, observational, cohort study, patients with achalasia treated by POEM received follow-up HRM. Associations between patient characteristics, POEM procedures, and post-POEM HRM findings, including integrated relaxation pressure (IRP) and distal contractile integral (DCI), were investigated. Furthermore, POEM procedure outcomes were compared with post-POEM HRM findings. RESULTS: Of 2171 patients, 151 (7.0%) showed residual high post-POEM IRP (≥26 mm Hg; Starlet [Starmedical Ltd, Tokyo, Japan]). In a multivariate analysis, high pre-POEM IRPs (odds ratio [OR], 24.3) and gastric myotomy >2 cm (OR, .22) were found to be positive and negative predictive factors of high post-POEM IRPs, respectively. Peristalsis recovery (DCI ≥500 mm Hg/cm/s, at least 1 swallow; Starlet) was visible in 121 of 618 patients (19.6%) who had type II to III achalasia. High pre-POEM IRP (OR, 2.65) and DCI ≥500 (OR, 2.98) predicted peristalsis recovery, whereas esophageal dilation (OR, .42) predicted a risk of no recovery. Extended myotomy did not reveal a significant impact on peristalsis recovery. High or low post-POEM IRP and DCI did not increase the incidence of clinical failure, reflux esophagitis, or symptomatic GERD. CONCLUSIONS: Extended gastric myotomy decreased IRP values, whereas peristalsis recovery depended on the characteristics of achalasia. A residual high post-POEM IRP does not necessarily mean clinical failure. Routine HRM follow-up is not recommended after POEM.

Esophageal mast cells may be associated with the perception of symptoms in patients with eosinophilic esophagitis.

BACKGROUND: Eosinophilic esophagitis (EoE) is a type 2 helper T-cell (Th2)-mediated allergic disease that involves mast cells. This study aimed to clarify the relationship between perception of symptoms and mast cell levels in patients with EoE. METHODS: We enrolled patients with asymptomatic esophageal eosinophilia (aEE) and those with symptomatic EoE. Immunofluorescence staining was performed on esophageal biopsy specimens to quantify mast cell-related molecules, such as tryptase, proteinase-activated receptor (PAR)-2, and vasoactive intestinal peptide receptor (VPAC)-1. RESULTS: We evaluated 28 and 58 patients with aEE and EoE, respectively. There were no significant differences in clinical and endoscopic features and peak eosinophil counts between both groups. Mast cell tryptase-positive areas were significantly higher in EoE than in aEE (4.9 [3.5-6.2] vs. 2.0 [1.2-3.4] %, p < 0.01). The number of PAR-2-positive cells was significantly higher in EoE than in aEE (14 [8.8-20.0] vs. 4 [2.8-8.0] cells/high-power field [HPF], p < 0.01). The number of VPAC-1-positive cells was significantly higher in the EoE group than in the aEE group (13 [8.8-16.0] vs. 6 [3.0-9.3] cells/HPF, p < 0.01). A positive correlation was observed between the numbers of PAR-2-positive cells and VPAC-1-positive cells (r = 0.851, p < 0.01). Moreover, mast cell tryptase-positive areas positively correlated with the number of PAR-2- and VPAC-1-positive cells (r = 0.352, p < 0.01; r = 0.355, p < 0.01, respectively). CONCLUSIONS: Esophageal mast cells and their receptors, PAR-2 and VPAC-1, may contribute to the perception of symptoms in patients with EoE.

Risk scoring system for the preprocedural prediction of the clinical failure of peroral endoscopic myotomy: a multicenter case-control study.

BACKGROUND: Peroral endoscopic myotomy (POEM) is effective for the management of achalasia and its variants; however, it can be ineffective in some patients. We aimed to develop and validate a risk scoring system to predict the clinical failure of POEM preoperatively. METHODS: Consecutive patients who underwent POEM in 14 high volume centers between 2010 and 2020 were enrolled in this study. Clinical failure was defined as an Eckardt score of ≥ 4 or retreatment. A risk scoring system to predict the short-term clinical failure of POEM was developed using multivariable logistic regression and internally validated using bootstrapping and decision curve analysis. RESULTS: Of the 2740 study patients, 112 (4.1 %) experienced clinical failure 6 months after POEM. Risk scores were assigned for three preoperative factors as follows: preoperative Eckardt score (1 point), manometric diagnosis (-4 points for type II achalasia), and a history of prior treatments (1 point for pneumatic dilation or 12 points for surgical/endoscopic myotomy). The discriminative capacity (concordance statistics 0.68, 95 %CI 0.62-0.72) and calibration (slope 1.15, 95 %CI 0.87-1.40) were shown. Decision curve analysis demonstrated its clinical usefulness. Patients were categorized into low (0-8 points; estimated risk of clinical failure < 5 %) and high risk (9-22 points; ≥ 5 %) groups. The proportions of clinical failure for the categories were stratified according to the mid-term outcomes (log-rank test, P < 0.001). CONCLUSIONS: This risk scoring system can predict the clinical failure of POEM preoperatively and provide useful information when making treatment decisions.