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Purpose: Periostin, an extracellular matrix protein closely related to mechanical stress, inflammation, and ageing, has been implicated in intervertebral disc degeneration (IVDD) in basic research. However, it has not been examined in clinical cases. This study aimed to evaluate the association between IVDD severity and serum periostin concentration as well as to analyse potential associations between IVDD and clinical and demographic factors. Methods: This retrospective cohort study included 198 patients who underwent lumbar disc herniation and lumbar canal stenosis between January 2020 and December 2022. The severity of IVDD was evaluated using the Pfirrmann grading, whereas serum periostin levels were measured using ELISA kits. Clinical demographics, including age, sex, body mass index, comorbidities, psoas muscle index, and spinal disease, were also recorded. Results: This study demonstrated a significant correlation between high serum periostin levels and IVDD severity, as indicated by a high cumulative Pfirrmann score. Serum periostin levels were identified as an independent risk factor for IVDD in a multivariate regression model. Correlation analysis showed a correlation between periostin levels and Pfirrmann grade at each lumbar level (ρ = 0.458–0.550, p < 0.001) and a strong correlation with cumulative Pfirrmann score (ρ = 0.690, p < 0.001). Conclusion: The higher the serum periostin level, the higher the cumulative Pfirrmann score. Multivariate analysis showed that serum periostin was an independent risk factor for IVDD. Periostin levels may be a clinically suitable and useful biomarker for diagnosing IVDD, estimating disease progression and activity, providing prognostic information, and evaluating treatment options. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Previous studies have shown that the Valsalva maneuver (VM) causes spinal canal object movements. We hypothesized that this occurs because of cerebrospinal fluid (CSF) flow generated from intradural space reduction. Previous studies using myelograms reported lumbar CSF space changes during inspiration. However, no similar studies have been conducted using modern MRI. Therefore, this study analyzed intradural space reduction during the VM using cine magnetic resonance imaging (MRI). Methods: The participant was a 39-year-old, healthy, male volunteer. Cine MRI involved fast imaging employing steady-state acquisition cine sequence during three resting and VM sets for 60 s each. The axial plane was at the intervertebral disc and vertebral body levels between Th12 and S1 during cine MRI. This examination was performed on 3 separate days; hence, data from nine resting and VM sets were available. Additionally, two-dimensional myelography was performed during rest and the VM. Results: Intradural space reduction was observed during the VM using cine MRI and myelography. The intradural space cross-sectional area during the VM (mean: 129.3 mm2; standard deviation [SD]: 27.4 mm2) was significantly lower than that during the resting period (mean: 169.8; SD: 24.8; Wilcoxon signed-rank test, P < 0.001). The reduction rate of the vertebral body level (mean: 26.7%; SD: 9.4%) was larger than that of the disc level (mean: 21.4%; SD: 9.5%; Wilcoxon rank sum test, P = 0.0014). Furthermore, the reduction was mainly observed on the ventral and bilateral intervertebral foramina sides at the vertebral body and intervertebral disc levels, respectively. Conclusion: The intradural space was reduced during the VM, possibly because of venous dilatation. This phenomenon may be associated with CSF flow, intradural object movement, and nerve compression, potentially leading to back pain. [ABSTRACT FROM AUTHOR]

Objective: To confirm the relationship between lumbar spinal stenosis (LSS) and cauda equina movement during the Valsalva maneuver. Materials and methods: Two radiologists at our institution independently evaluated cauda equina movement on pelvic cine MRI, which was performed for urethrorrhea after prostatectomy or pelvic prolapse in 105 patients (99 males; mean age: 69.0 [range: 50–78] years), who also underwent abdominopelvic CT within 2 years before or after the MRI. The qualitative assessment of the cine MRI involved subjective determination of the cauda equina movement type (non-movement, flutter, and inchworm-manner). The severity of LSS on abdominopelvic CT was quantified using our LSS scoring system and performed between L1/2 and L5/S1. We calculated the average LSS scores of two analysts and extracted the worst scores among all levels. Results: Cauda equina movement was observed in 15 patients (14%), inchworm-manner in 10 patients, and flutter in five patients. Participants with cauda equina movement demonstrated significantly higher LSS scores than those without movement (P < 0.001, Wilcoxon's rank-sum test). A significant difference was observed in the worst LSS scores between participants without movement and those with inchworm-manner movement (P < 0.001, Bonferroni's corrected). There were no significant differences between participants without movement and those with flutter movement (P = 0.3156) and between participants with flutter movement and those with inchworm-manner movement (P = 0.4843). Conclusion: Cauda equina movement in cine MRI during the Valsalva maneuver is occasionally observed in patients with severe LSS, and may be associated with pathogenesis of redundant nerve roots. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Purpose: It remains unclear whether musculoskeletal diseases are risk factors for dementia development. This prospective cohort study of community-dwelling residents aimed to clarify the impact of lumbar spinal stenosis (LSS) on dementia development. Methods: We included participants aged ≥ 65 years from the Locomotive Syndrome and Health Outcomes in the Aizu cohort study. LSS was diagnosed using the validated LSS diagnostic support tool. Dementia development between 2008 and 2015 was investigated using official long-term care insurance certification data. We analysed the effects of LSS on dementia development after adjusting for potential confounders, like age, sex, diabetes, depressive symptoms, hip and knee joint osteoarthritis, daily activity, and smoking habit. Results: We included 1220 patients in the final analysis. The incidence of dementia was significantly higher in the LSS group [48 of 444 (10.8%)] than in the control group [34 of 776 (4.4%)]. Multivariable analysis using multiple imputations revealed that the confidence interval for the adjusted odds ratio of LSS for dementia development was 1.87 (95% confidence interval; 1.14–3.07). Conclusion: We clarified that LSS is an independent risk factor for dementia development. Our findings suggest the importance of considering the risk of dementia in the decision-making process for the treatment of LSS. [ABSTRACT FROM AUTHOR]

Background: The pathogenesis of eosinophilic esophagitis involves immunoglobulin G4 (IgG4) deposition. However, the relationship between IgG4 and eosinophilic gastroenteritis (EGE) is unclear. Aims: To investigate gastrointestinal deposition of IgG4 in EGE. Methods: Biopsies of the esophagus, stomach, and small intestine were evaluated in patients with and without EGE. Immunohistochemical staining for IgG4 was performed, and the proportions of the stained areas were compared. Sera from patients with EGE were assayed for food-specific IgG4, including egg white, wheat, rice, soy, and cow milk. Results: Seventeen patients were included in this study (EGE group, n = 10; control group, n = 7). Compared with the control group, the proportion of IgG4-stained area in the EGE group was approximately threefold higher (40.2% [32.3–49.5]) vs. 12.1% [4.0–21.9], p = 0.014) in the esophagus, fivefold higher in the stomach (17.3% [11.1–26.2] vs. 3.7% [1.5–5.2], p = 0.014), and sixfold higher in the small intestine (28.0% [15.0–33.2] vs. 4.5% [2.6–9.8], p = 0.019). There was no significant association between the proportion of IgG4-stained area and the number of infiltrating eosinophils. Serum egg white-specific IgG4 levels were correlated with the proportion of IgG4-stained areas in the small intestine (R = 0.7, p = 0.035). Conclusions: IgG4 accumulated within the gastrointestinal mucosa in EGE. The positive correlation between serum egg white-specific IgG4 levels and the proportion of IgG4-stained areas in the small intestine suggests a role for IgG4 in the disease pathophysiology. [ABSTRACT FROM AUTHOR]

Metabolic syndrome and lumbar spinal stenosis (LSS) are common age-related diseases. However, the causal relationship between them remains unclear. This study aimed to identify the effects of LSS on metabolic syndrome incidence in community-dwelling adults. This prospective cohort study included participants of the Aizu cohort study (LOHAS) aged < 75 years as of 2008. Participants with metabolic syndrome at baseline were excluded. The primary outcome measure was metabolic syndrome incidence, and the main explanatory variable was the presence of LSS, as assessed by a self-reported questionnaire. A multivariate Cox proportional hazard regression model was used to estimate hazard ratios (HRs) for metabolic syndrome incidence during the 6-year follow-up period. Complete-case analyses were compared with the multiple imputation results. Among 1599 participants, 1390 complete cases were analyzed (mean [SD] age 62.3 [9.0] years; females, 734 [52.8%]). Among those participants, 525 (37.8%) developed metabolic syndrome during the follow-up of 3.89 [1.96] years. The presence of LSS was associated with developing metabolic syndrome (HR, 1.41; 95% confidence interval [CI] 1.02–1.95). Multiple imputation results showed similar trends of those having complete-case data (HR, 1.47; 95% CI 1.08–2.00). This finding suggests the importance of prevention and management of LSS in community settings. [ABSTRACT FROM AUTHOR]

Background: Endoscopic submucosal dissection (ESD) is becoming widely popular as a less invasive treatment option for superficial esophageal squamous cell carcinoma. However, data on long-term survival after esophageal ESD in patients with severe comorbidities are limited. This study aimed to evaluate long-term survival after ESD in such patients. Methods: Altogether, 584 consecutive patients underwent esophageal ESD at our institution from May 2004 to September 2016. Based on the American Society of Anesthesiologists Physical Status (ASA-PS) classification system, patients were grouped according to severe (ASA-PS ≥ 3) or non-severe comorbidities (ASA-PS 1/2). The overall survival (OS), disease-specific survival (DSS), and risk factors for mortality were compared between the groups using a propensity score matching analysis. Results: In a matched cohort of 69 pairs, the 5-year OS rate was poorer in ASA-PS 3 patients than in ASA-PS 1/2 patients (63.9% vs. 92.5%, P < 0.01), while the 5-year DSS rate was similar between the groups (100% vs. 100%). The mortality rate was significantly higher in ASA-PS 3 patients than in ASA-PS 1/2 patients (hazard ratio 3.47; 95% confidence interval 1.79–6.74; P < 0.01). Death due to exacerbation of comorbidities was significantly more frequent in ASA-PS 3 patients than in ASA-PS 1/2 patients (42.4% vs. 8.3%, P < 0.04). Conclusion: Because of the exacerbation of comorbidities, patients with severe comorbidities had poorer long-term outcomes after esophageal ESD than those with non-severe comorbidities. Further studies will be necessary to evaluate esophageal ESD in patients with severe comorbidities. [ABSTRACT FROM AUTHOR]

A thorough understanding of lumbar segmental motion is valuable to treat patients with degenerative lumbar disease, but kinematics associated with indicators of lumbar intervertebral instability [traction spur, Modic changes (MCs) and vacuum phenomenon (VP)] in the lumbar spine have not been well understood. The purpose of this study is to evaluate the relationships between traction spur, MCs and VP to radiographic measurements in the lumbar spine. A total of 525 lumbar discs from L1-2 to L5-S1 of 105 patients were evaluated. The sagittal translation (ST) and sagittal angulation were measured from the radiographs taken flexion–extension. The anterior disc height (ADH) was measured from the lateral radiographs, and ΔADH was measured as the difference from supine to sitting position. Logistic regression analyses were used to detect the association between the existence of traction spur, MCs and VP and related factors. Multivariate analysis showed that the traction spur was significantly related to translational motion (ST > 2 mm, OR 4.74) and the VP was significantly related to vertical motion (ΔADH > 3 mm, OR 1.94). These results suggest that the segments with traction spur and VP should be evaluated carefully because these may be a sign of lumbar intervertebral instability. [ABSTRACT FROM AUTHOR]

Emerging anti-tumor necrosis factor (TNF)-α antibodies therapy changed treatment strategy to inflammatory bowel diseases because of the efficacy. However, TNF-α inhibitor can be associated with an increased risk of infectious complications, especially tuberculosis. A 71-year-old female with steroid-dependent ulcerative colitis (UC) was admitted due to relapse of UC with endoscopically severe active. Golimumab and adjunctive prednisolone started with 30 mg daily resulted in clinical remission. However, she had general fatigue and fever at the time of seventh injection of golimumab without abdominal symptoms. Based on positive interferon-gamma release assay, polymerase chain reaction positive for tuberculosis (TB) in pleural fluid, and chest computed tomography, she was diagnosed as tuberculous pleuritis. Standard anti-TB treatment (isoniazid, rifampicin, ethambutol, and pyrazinamide) was started without cessation of golimumab, because cessation of TNF-α inhibitors during anti-TB treatment could cause the paradoxical response by skewing from regulatory to inflammatory immune responses. However, four weeks after initiation of anti-TB treatment, she got fever-up and pleural effusion increased. We then started prednisolone 30 mg daily as diagnosis of paradoxical response, resulting in improving the symptoms. This is a suggestive case of paradoxical response during anti-TB treatment despite continuous TNF-α inhibitors. [ABSTRACT FROM AUTHOR]

Purpose: Uncorrected refractive error (URE) is the leading cause of vision impairment and the second leading cause of blindness. It is a major public health challenge worldwide. However, the current status of URE in Japan is unclear. Study design: Cross-sectional study. Methods: In 2012, a population-based cross-sectional study was conducted among community dwellers aged 40 years and older who received health check-ups in Minamiaizu and Tadami, Fukushima Prefecture, Japan. URE was considered when the presenting visual acuity in the better-seeing eye was < 0.5 and when visual acuity improved more than 1 line with refractive correction in the better-seeing eye. We estimated the age-specific prevalence of URE, and calculated the p-value for trend to examine the linear pattern of the association of the prevalence of URE and age. Results: This analysis included 2952 participants. The mean age (standard deviation [SD]) of the study population was 69.10(9.67) years and 57.79% were women. The overall prevalence of URE was 10.90% (95% CI, 9.77–12.05%). Prevalence by age category was 5.00% (95% CI, 2.03–10.03%), 6.09% (95% CI, 3.59–9.58%), 7.02% (95% CI, 5.49–8.81%), 11.96% (95% CI, 10.15–13.97%), and 22.39% (95% CI, 18.41–26.78%) for 40–49 years, 50–59 years, 60–69 years, 70–79 years, and 80 years or older, respectively (p-for trend, < 0.001). Conclusions: The prevalence of URE was 10.9% and exceeded 20%, especially in individuals older than 80 years. Given the correlation between increasing incidence of URE and increase in age, public health intervention to promote awareness of URE is important, especially for the older population. [ABSTRACT FROM AUTHOR]

Purpose: To determine whether abnormalities of the sagittal modifiers (SMs) of the Scoliosis Research Society (SRS)-Schwab classification truly reflect back pain (BP)-specific quality of life (QOL), it is necessary to examine their dose–response relationships and to determine clinically impactful thresholds for declines in BP-specific QOL. This study aimed to analyse the continuous dose–response relationship between each SM and BP-specific QOL. Methods: This cross-sectional study, using data from a Japanese population-based cohort study, included 519 community-dwelling residents aged ≥ 50 years who participated in the annual health examination. The participants completed the Roland–Morris Disability Questionnaire (RDQ) on BP-specific QOL. Spino-pelvic alignment based on SMs was assessed by whole-spine X-ray examinations. We fitted general linear models with or without nonlinear terms to estimate the dose–response relationship between each SM and BP-specific QOL. Results: Pelvic tilt, pelvic incidence minus lumbar lordosis (PI-LL), and sagittal vertical axis showed dose–response relationships with BP-specific QOL measured as the RDQ score. PI-LL was most likely to predict a minimally clinically important RDQ score when its value exceeded the 90th percentile. A nonlinear relationship between PI-LL and the BP-specific QOL score was found. RDQ increased when PI-LL exceeded 10°. Conclusion: PI-LL might be the most sensitive of the three modifiers of the SRS-Schwab classification for determining BP-specific QOL. Moreover, BP-specific QOL worsens rapidly when the compensatory mechanism against malalignment exceeds a critical value. Therefore, we suggest that traditional classifications and surgical strategies should be re-examined regarding the dose-dependent abnormalities of the SMs to develop a more reliable classification strategy. [ABSTRACT FROM AUTHOR]

Purpose: With spinal deformities, mental health can deteriorate due to sagittal imbalance of the spine. The purpose of this study was to clarify the relationship between sagittal imbalance and symptoms of depression among local residents in the community. Methods: This study used data from the Locomotive Syndrome and Health Outcomes in Aizu Cohort Study (LOHAS) in 2010. The sagittal vertical axis (SVA) was identified as an indicator of sagittal imbalance. Symptoms of depression were assessed using the 5-item version of the Mental Health Inventory. Participants were classified into three categories based on the SVA balance as normal (< 40 mm), moderate imbalance (40–95 mm), and severe imbalance (> 95 mm). To evaluate the relationship between sagittal imbalance of the spine and symptoms of depression, the adjusted risk ratio (RR) and the 95% confidence interval (CI) were calculated using a generalized linear model with Poisson link. Results: There were 786 participants included in the statistical analysis. Overall, the mean age was 68.1 y (standard deviation, 8.8 y), and 39.4% were men. The prevalence of symptoms of depression by SVA category was 18.6% for normal, 23.8% for moderate, and 40.6% for severe. On multivariate analysis, the RR of SVA for symptoms of depression compared to the normal category was 1.12 (95% CI 0.7–1.70) for the moderate category and 2.29 (95% CI 1.01–5.17) for the severe category. Conclusion: In local community residents, sagittal imbalance had a significant association with symptoms of depression. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the prevalence and factors associated with uncorrected presbyopia among rural community dwellers in Japan. Study design: A population-based cross-sectional study was conducted in 2011 among community dwellers aged 40–74 years who received specific health checkups in Minamiaizu and Tadami, Fukushima Prefecture, Japan. Methods: Uncorrected presbyopia was considered as when the distance-corrected visual acuity in the better eye was ≥0.5 and the near-presenting visual acuity in the better eye was <0.4, regardless of distance refractive status. Multiple logistic regression analysis was employed to calculate the odds ratios (ORs) for uncorrected presbyopia and to adjust for possible confounders. Results: A total of 2054 individuals participated in the specific health checkups. In the 1156 individuals (response rate: 56.28%) analyzed in the study, the mean (SD) age was 63.0 (8.7) years, the percentage of women was higher (57.87%), and the prevalence of uncorrected presbyopia was 26.38% (95% CI 23.86%–29.03%). Multivariate analysis revealed that the factors associated with uncorrected presbyopia were older age (adjusted OR: 1.054 [95% CI: 1.034–1.075]), female sex (adjusted OR: 1.388 [95% CI: 1.006–1.915]), and distance-presenting vision impairment (adjusted OR: 2.651 [95% CI: 1.697–4.143]). Conclusion: Approximately one-quarter of the participants in this study from a rural population of Japan did not have adequate near vision. It is recommended that a public health intervention should be enacted to correct presbyopia, especially in the older age group, women, and those with uncorrected refractive errors. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the incidence and characteristics of subsequent vertebral fracture after osteoporotic vertebral fractures (OVFs) and identify risk factors for subsequent vertebral fractures. Methods: This post-hoc analysis from a prospective randomized multicenter trial included 225 patients with a 48-week follow-up period. Differences between the subsequent and non-subsequent fracture groups were analyzed. Results: Of the 225 patients, 15 (6.7%) had a subsequent fracture during the 48-week follow-up. The annual incidence of subsequent vertebral fracture after fresh OVFs in women aged 65–85 years was 68.8 per 1000 person-years. Most patients (73.3%) experienced subsequent vertebral fractures within 6 months. At 48 weeks, European Quality of Life-5 Dimensions, the Japanese Orthopedic Association Back Pain Evaluation Questionnaire pain-related disorder, walking ability, social life function, and lumbar function scores were significantly lower, while the visual analog scale (VAS) for low back pain was higher in patients with subsequent fracture. Cox proportional hazards analysis showed that a VAS score ≥ 70 at 0 weeks was an independent predictor of subsequent vertebral fracture. After adjustment for history of previous fracture, there was a ~ 67% reduction in the risk of subsequent vertebral fracture at the rigid-brace treatment. Conclusion: Women with a fresh OVF were at higher risk for subsequent vertebral fracture within the next year. Severe low back pain and use of soft braces were associated with higher risk of subsequent vertebral fractures. Therefore, when treating patients after OVFs with these risk factors, more attention may be needed for the occurrence of subsequent vertebral fractures. Level of evidence: III [ABSTRACT FROM AUTHOR]

Background: Endoscopic submucosal dissection (ESD) is accepted as the standard treatment for early-stage esophageal neoplasia. However, esophageal perforation may occur, leading to mediastinitis and pneumothorax, which occasionally require emergency surgery. Moreover, failure of en bloc resection causes local recurrence. However, studies on the predictors of such difficulties during ESD are limited. Hence, we evaluated the predictors associated with the difficulty of ESD for esophageal neoplasia including failure of en bloc resection or perforation.Methods: Data of 549 consecutive patients who were treated with ESD between May 2004 and March 2016 at a single institution were retrospectively studied. Exclusion criteria were the presence of metachronous esophageal neoplasia or missing data. The primary outcome was determining the predictors associated with the difficulty of ESD for esophageal neoplasia including failure of en bloc resection or perforation.Results: Altogether, 543 patients with 736 lesions were evaluated. Failure of en bloc resection occurred in 6 patients (1.1%) with 6 lesions, and perforation occurred in 11 patients (2.0%) with 11 lesions (1.5%). Multivariate logistic regression analysis showed that large lesion diameter (odds ratio [OR] 1.49; 95% confidence interval [CI] 1.21-1.84; p < 0.001) and previous chemoradiotherapy (OR 5.24; 95% CI 1.52-18.06; p = 0.009) were independent predictive factors.Conclusions: Larger lesions and previous chemoradiotherapy for esophageal cancer increased the risk for failure of en bloc resection or perforation in patients who underwent esophageal ESD. [ABSTRACT FROM AUTHOR]

Background: Gastric microbiome, other than Helicobacter pylori, plays a role in the tumorigenesis of gastric cancer (GC). Patients who undergo endoscopic submucosal dissection for early GC have a high risk of developing metachronous GC even after successful eradication of H. pylori. Thus, we investigated the microbial profiles and associated changes in such patients after the eradication of H. pylori. Methods: A total of 19 H. pylori-infected patients with early GC who were or to be treated by endoscopic resection, with paired biopsy samples at pre- and post-eradication therapy, were retrospectively enrolled. Ten H. pylori-negative patients were enrolled as controls. Biopsy samples were analyzed using 16S rRNA sequencing. Results: H. pylori-positive patients exhibited low richness and evenness of bacteria with the deletion of several genera, including Blautia, Ralstonia, Faecalibacterium, Methylobacterium, and Megamonas. H. pylori eradication partially restored microbial diversity, as assessed during a median follow-up at 13 months after eradication therapy. However, post-eradication patients had less diversity than that in the controls and possessed a lower abundance of the five genera mentioned above. The eradication of H. pylori also altered the bacterial composition, but not to the same extent as that in controls. The microbial communities could be clustered into three separate groups: H. pylori-negative, pre-eradication, and post-eradication. Conclusion: Changes in dysbiosis may persist long after the eradication of H. pylori in patients with a history of GC. Dysbiosis may be involved in the development of both primary and metachronous GC after the eradication of H. pylori in such patients. [ABSTRACT FROM AUTHOR]

Background: Eosinophilic esophagitis (EoE) is considered to be an immunoglobulin E (IgE)-mediated allergic disorder. Our goal was to examine IgE-mediated allergic sensitization patterns in patients with esophageal eosinophilia (EE).Methods: We enrolled subjects with EE who underwent evaluation with a diagnostic panel to document multiple allergen-specific IgEs. Statistically significant groups were identified by cluster analysis. We also defined allergens based on their characteristics including outdoor, indoor, plant, and animal allergens.Results: We classified patients with EE into 3 distinct groups, including cluster 1 (n = 62) who were minimally sensitized to most allergens except pollen and house dust, cluster 2 (n = 30) who were hypersensitized to outdoor and plant allergens, and cluster 3 (n = 15) who were hypersensitized to most allergens, most notably to indoor and animal allergens. Dysphagia reported among those in clusters 1, 2, and 3 at 35.5%, 46.7%, and 73.3%, respectively, (p = 0.028) and EoE endoscopic reference scores (EREFS) at 3.0, 6.0, and 8.0, respectively, (p < 0.001) differed significantly between the 3 clusters. Those in cluster 3 had a significantly higher prevalence of dysphagia (35.5% vs. 73.3%, p = 0.030), and higher EREFS with respect to rings (0.3 vs. 0.9, p = 0.003) and strictures (0.0 vs. 0.13, p = 0.011) compared to those in cluster 1.Conclusions: IgE-mediated allergic sensitization patterns are associated with clinical features of patients with EE. Use of a diagnostic panel that detects multiple allergen-specific IgEs can help to explain the heterogeneous phenotype of this patient cohort. [ABSTRACT FROM AUTHOR]

Background: Eosinophilic esophagitis (EoE) is a chronic allergic disease with esophageal symptoms and intraepithelial eosinophil infiltration. Effects of potassium-competitive acid blockers (P-CABs) on EoE have not been elucidated. We aimed to examine and compare the effects of P-CABs and PPIs on symptomatic, endoscopic, and histological responses of patients with EoE. Methods: We analyzed 118 EoE patients who received PPI or P-CAB therapy with rabeprazole 10 mg (RPZ10, N = 22), rabeprazole 20 mg (RPZ20, N = 34), esomeprazole 20 mg (EPZ20, N = 25), or vonoprazan 20 mg (VPZ20, N = 33). We evaluated symptomatic responses by classifying the patients into three groups: complete relief, partial relief, and no change. Endoscopic responses were evaluated using the endoscopic reference score (EREFS) following PPI or P-CAB therapy. Histological responses were evaluated by determining eosinophil counts in esophageal biopsy samples and classifying the patients into two groups: complete remission [0/1 eosinophil/high-power field (eos/HPF)] and remission (< 15 eos/HPF). Results: There were no differences among the therapy groups in terms of clinical characteristics, endoscopic findings, and histological findings of the patients before treatment. The rate of complete relief in clinical symptoms was 54.5% in the RPZ10 group, 64.7% in the RPZ20 group, 72.0% in the EPZ20 group, and 75.7% in the VPZ20 group. There were no significant differences in the therapeutic effect among the therapy groups. Similarly, endoscopic and histological complete remission rates were not significantly different among the therapy groups. Conclusions: Vonoprazan showed similar efficacy to PPIs in EoE. [ABSTRACT FROM AUTHOR]

Purpose: No study has investigated the clinical and radiographic risk factors for the deterioration of quality of life (QOL) beyond 6 months after osteoporotic vertebral fractures (OVF). The purpose of this study was to identify the predictors associated with poor QOL improvement after OVF. Methods: This post hoc analysis included 166 women aged 65–85 years with acute 1-level OVFs. For the patient-reported outcome measures, scores on the European Quality of Life-5 Dimensions (EQ-5D) scale, and visual analogue scale (VAS) for low back pain were used. Lateral radiography at 0, 12, and 48 weeks and magnetic resonance imaging (MRI) at enrollment and at 48 weeks were performed. The associations between baseline variables with change scores for EQ-5D were investigated using a multiple linear regression model. Results: Univariate analysis showed that time since fracture, EQ-5D score, and VAS for low back pain at 0 week showed significant association with increased EQ-5D score from 0 to 48 weeks. According to the multiple regression analysis, the following equation was obtained: increased EQ-5D score from 0 to 48 weeks = 1.305 – 0.978 × EQ-5D at 0 week – 0.021 × VAS for low back pain at 0 week – 0.006 × age + (fluid-intensity T2-weighted MR image patterns: − 0.037, except for fluid-intensity T2-weighted MR image patterns: + 0.037). Conclusion: In conclusion, older patients with severe low back pain and fluid-intensity T2-weighted MR image patterns were more likely to have lower QOL improvements after OVFs and may therefore need extra support to improve QOL [ABSTRACT FROM AUTHOR]

Background: MicroRNAs (miRNAs) in exosomes represent disease-specific profiles and are applied as biomarkers in oncology. However, in functional dyspepsia (FD), the role of exosomal miRNAs has not been fully elucidated. Aims: To investigate exosomal miRNAs as potential biomarkers of FD using liquid biopsy. Methods: This retrospective cohort study included 11 subjects with FD and 11 age- and sex-matched healthy controls (HCs). We collected gastric juice and isolated exosomal miRNAs. In a discovery cohort, expression levels of 2565 miRNAs were evaluated by 3D-Gene® microarray. miRNA expression profiles from exosomes of subjects with FD and HCs were compared by two normalization methods: (1) global normalization and (2) normalization by internal control. Subsequently, in a validation cohort, the expression levels of miRNAs were validated by quantitative reverse transcription PCR (RT-qPCR). Results: Through microarray analysis using the two methods, we identified 39 miRNAs that were consistently and significantly downregulated in FD cases compared with those in HCs. Of these, 12 miRNAs (hsa-miR-933, hsa-miR-345-5p, hsa-miR-708-5p, hsa-miR-203a-3p, hsa-miR-619-5p, hsa-miR-4294, hsa-miR-4481, hsa-miR-196a-5p, hsa-miR-3918, hsa-miR-372-3p, hsa-miR-658, and hsa-miR-3654) were further validated by RT-qPCR. Our results indicated that hsa-miR-933 was significantly downregulated in FD compared with HCs (0.317 ± 0.205-fold, P = 0.0317). Furthermore, the expression level of hsa-miR-933 was negatively associated with dyspepsia score and the frequency of epigastric pain and/or burning (P < 0.01, r = − 0.835; P = 0.0280, r = − 0.688, respectively). Conclusions: Exosomal hsa-miR-933 in gastric juice could be a candidate biomarker for FD. [ABSTRACT FROM AUTHOR]

Loss-of-function mutations in the solute carrier organic anion transporter family, member 2a1 gene (SLCO2A1), which encodes a prostaglandin (PG) transporter, have been identified as causes of chronic nonspecific multiple ulcers in the small intestine; however, the underlying mechanisms have not been revealed. We, therefore, evaluated the effects of systemic knockout of Slco2a1 (Slco2a1−/−) and conditional knockout in intestinal epithelial cells (Slco2a1ΔIEC) and macrophages (Slco2a1ΔMP) in mice with dextran sodium sulphate (DSS)-induced acute colitis. Slco2a−/− mice were more susceptible to DSS-induced colitis than wild-type (WT) mice, but did not spontaneously develop enteritis or colitis. The nucleotide-binding domain, leucine-rich repeats containing family, pyrin domain-containing-3 (NLRP3) inflammasome was more strongly upregulated in colon tissues of Slco2a−/− mice administered DSS and in macrophages isolated from Slco2a1−/− mice than in the WT counterparts. Slco2a1ΔMP, but not Slco2a1ΔIEC mice, were more susceptible to DSS-induced colitis than WT mice, partly phenocopying Slco2a−/− mice. Concentrations of PGE2 in colon tissues and macrophages from Slco2a1−/− mice were significantly higher than those of WT mice. Blockade of inflammasome activation suppressed the exacerbation of colitis. These results indicated that Slco2a1-deficiency increases the PGE2 concentration, resulting in NLRP3 inflammasome activation in macrophages, thus exacerbating intestinal inflammation. [ABSTRACT FROM AUTHOR]

Background: Gastroesophageal reflux disease (GERD) is strongly associated with sleep disturbances. Clock genes harmonize circadian rhythms by their periodic expression and regulate several physiological functions. However, the association between clock genes and GERD is still unknown.Aims: We investigated whether reflux esophagitis affects circadian variability of clock genes in the esophagus and other organs using a rat reflux esophagitis model.Methods: Reflux esophagitis was induced in 7-week-old male Wistar rats. Sham-operated rats were used as controls. Rats were killed at 09:00 (light period) and 21:00 (dark period) 3 days (acute phase) and 21 days (chronic phase) after induction of esophagitis. The expression levels of clock gene mRNAs such as Per1, Per2, Per3, Cry1, Cry2, Arntl, and Clock in the esophagus were investigated by qPCR. Arntl expression was examined in stomach, small intestine, colon, and liver tissues. Serum melatonin and IL-6 levels were measured by ELISA.Results: Histological examination of reflux esophagitis mainly revealed epithelial defects with marked inflammatory cell infiltration in the acute phase and mucosal thickening with basal cell hyperplasia in the chronic phase. Circadian variability of clock genes, except Cry1, was present in the normal esophagus and was completely disrupted in reflux esophagitis during the acute phase. The circadian variability of Per2, Per3, and Arntl returned to normal, but disruption of Per1, Cry2, and Clock was present in the chronic phase. Disruption of circadian variability of Arntl was observed in the esophagus, as well as in the stomach, small intestine, and liver tissues in reflux esophagitis during the acute phase. There were no significant differences in serum melatonin and IL-6 levels between control and reflux esophagitis animals in both acute and chronic phases.Conclusions: Disruption to circadian variability of clock genes may play a role in the pathogenesis of GERD. [ABSTRACT FROM AUTHOR]

Background: Esophageal eosinophilia (EE) is a basal condition of eosinophilic esophageal disorders including eosinophilic esophagitis (EoE) and asymptomatic EE. EoE is considered as an allergic disorder, while it is unclear whether other non-allergic conditions are involved in the pathophysiology of EE. The aim of this study is to investigate the non-allergic risk factors for EE. Methods: This cross-sectional study included subjects who underwent esophagogastroduodenoscopy on a medical health check-up. We compared clinical characteristics between subjects with EE (n = 27) and those without EE (n = 5937). Results: The detection rate of EE was 0.45% (27/5964 persons). Of 27 subjects with EE, 20 subjects were symptomatic and 7 were asymptomatic. On univariate analysis, subjects with EE significantly had higher body mass index (BMI) compared to those without EE; 23.4 (4.4) vs 22.3 (4.5) kg/m2, median (interquartile range), p = 0.005. Endoscopic findings revealed that subjects with EE had significantly higher proportion of hiatal hernia (29.6% vs 14.7%; p = 0.049). Subjects with EE were significantly younger and had higher proportion of bronchial asthma; 45 (11.5) vs 51 (18) years, p = 0.013; 25.9% vs 5.2%, p < 0.001, respectively. Multivariate analysis showed that subjects with EE were positively associated with BMI [odds ratio (OR) 1.11; 95% confidence interval (CI) 1.03–1.20; p = 0.010) and hiatal hernia (OR 2.63; 95% CI 1.12–6.18; p = 0.026) compared to those without EE. On trend test, advanced BMI classification had significant trend for increased prevalence of EE (p = 0.002). Conclusions: Obesity and hiatal hernia may be non-allergic risk factors for EE in Japanese adults. [ABSTRACT FROM AUTHOR]

Background: Recently, endoscopic submucosal dissection (ESD) for early gastric cancer (EGC) has been performed on patients with severe comorbidities because it is less invasive, although little is known regarding long-term outcomes. This study aimed to assess the long-term outcomes of ESD for patients with severe and non-severe comorbidities. Methods: We enrolled 1081 patients who underwent ESD for EGC between February 2004 and June 2013. Based on the American Society of Anesthesiologists Physical Status (ASA-PS) classification, we defined patients with severe and non-severe comorbidities as ASA-PS 3 and 1/2, respectively. We retrospectively compared the overall survival, risk factors for mortality, and adverse events between these two groups using propensity score matching and inverse probability of treatment weighting. Results: A total of 488 patients met the eligibility criteria. After matching, the ASA-PS 3 group showed a significantly shorter survival than the ASA-PS 1/2 group (5-year overall survival rate, 79.1 vs. 87.7%; p < 0.01). In addition, only the ASA-PS 3 group had a significant risk factor for mortality using both the Cox analysis [hazard ratio (HR), 2.56; 95% confidence interval (CI) 1.18–5.52; p = 0.02] and the IPTW method (HR, 3.14; 95% CI 1.91–5.14; p < 0.01). There was no significant difference in adverse events after matching between the two groups (p = 0.21). Conclusions: The long-term outcome of gastric ESD for patients with severe comorbidities was worse than for those with non-severe comorbidities. Further studies will be necessary to determine if ESD is truly warranted in these patients. [ABSTRACT FROM AUTHOR]

Background: Although both eosinophilic esophagitis (EoE) and Barrett's esophagus (BE) are considered to be associated with T helper (Th) 2-mediated immune responses, the association between EoE and BE is unclear. We investigated the clinical relationship between EoE and BE. Methods: We conducted a single-center retrospective observational study. The study included 95 patients with EoE and randomly selected age- and sex-matched controls who underwent esophagogastroduodenoscopy during a medical health check-up at Osaka City University in a ratio of 1:2 for comparison. We compared the clinical characteristics and the prevalence rate of BE, reflux esophagitis (RE), hiatal hernia, and atrophic gastritis between EoE patients and controls by univariate analysis. Furthermore, we performed multivariate logistic regression analysis to investigate the association of these factors with EoE. Results: On univariate analysis, the prevalence rate of BE was significantly lower in patients with EoE than in controls (2.1% vs. 13.2%; p = 0.00528). In contrast, the prevalence rate of RE was higher in EoE patients than in controls, but it was not statistically significant (absence and Grades A, B, and C: 74.7%, 18.9%, 5.3%, and 1.1% vs. 83.7%, 12.6%, 3.7%, and 0%; p = 0.193, respectively). Multivariate analysis showed that BE was negatively associated with EoE (odds ratio: 0.132; 95% confidence interval: 0.0302–0.573; p = 0.00686). Conclusions: BE is negatively associated with EoE in Japanese subjects. The mechanism behind the inverse relationship between EoE and BE should be examined. [ABSTRACT FROM AUTHOR]

Distal esophageal spasm (DES) is a primary esophageal motility disorder. We encountered a rare case of DES accompanied by multiple esophageal diverticula. A 72-year-old woman complained of prolonged dysphagia and chest pain. A barium esophagogram showed multiple esophageal diverticula and significant contraction of the lower esophagus just above the cardia. Esophagogastroduodenoscopy revealed a corkscrew-like appearance, with spiral contractions and diverticula. High-resolution manometry revealed that the integrated relaxation pressure was normal; premature contractions were observed in ≥20% of the swallowing wave; the distal contractile integral was normal. She was diagnosed with DES according to the Chicago classification v 3.0. As smooth muscle relaxants were not effective, we decided to perform peroral endoscopic myotomy (POEM) to eliminate persistent esophageal contraction. After POEM treatment, her symptoms were markedly improved, and the Eckardt score significantly decreased from 11 points to 1. An esophagogram after POEM showed that barium flowed promptly into the stomach. The multiple esophageal diverticula were considered to be the result of false pulsion diverticulosis caused by excessive internal esophageal pressure, and this represented the most severe form of DES. POEM could be a new curative strategy for the most severe DES cases with multiple diverticula. [ABSTRACT FROM AUTHOR]

Introduction: Lumbar spinal stenosis (LSS) is a lumbar spinal disorder that causes leg symptoms and intermittent claudication. It is reported that the risk factors for low back pain include age, family history, smoking, obesity, work-related physical load, exercise, and depression. This was a multicenter, cross-sectional survey, and the aim of this study was to investigate the prevalence of LSS by age and the relationships between LSS and psychosocial factors and job satisfaction.Methods: This study enrolled subjects aged 50 years and over from a survey of LSS in 2177 hospitals and general practices nationwide. The clinical characteristics of the LSS and non-LSS groups were compared using the χ2 test, and the multivariate logistic regression analysis was performed to examine associations between exercise, perceived stress, strenuous use of the low back or legs, job satisfaction, and LSS.Results: In total, 18,642 patients (8338 males, 10,267 females) were analyzed. The rate of LSS was 38.3% and it increased with age. Regular exercise was less common among those in the LSS group than those in the non-LSS group (p<0.001). Satisfaction in all job-related items was less in the LSS group than in the non-LSS group (p<0.001). The odds for having LSS were higher in subjects having perceived stress and strenuous use of the low back or legs (p=0.001). The odds ratios of heart diseases and hypertension (p<0.001) were higher in the LSS group.Conclusion: This study investigated factors associated with LSS. The prevalence of LSS increased with age. Perceived stress and strenuous use of the low back or legs might be associated with LSS, and job satisfaction was lower with LSS. [ABSTRACT FROM AUTHOR]

Purpose: Limaprost, a prostaglandin E analog, has vasodilatory properties and increases blood flow of the nerve root. However, it has not been clarified whether limaprost affects pain sensation associated with radiculopathy due to lumbar spinal stenosis (LSS). The aim of this study was to compare the efficacy of oral limaprost with nonsteroidal anti-inflammatory drugs (NSAIDs) for radiculopathy. Methods: We performed a multicenter prospective randomized trial. Patients with LSS who had radicular-type neurologic intermittent claudication assessed based on a self-reported diagnostic support tool were randomized into three treatment groups. Limaprost, NSAIDs, or limaprost plus NSAIDs were administered orally for 6 weeks. Leg pain, low back pain (LBP) and the associated symptoms were assessed by a numerical rating scale (NRS) both at rest and on movement as well as the Roland-Morris Disability Questionnaire (RDQ) and Short Form (SF)-36. Results: Sixty-one patients were enrolled in the study. Each treatment finally reduced radicular pain, and the improvement was prominent in a combination treatment. There were no significant differences in radicular pain among three groups at final follow-up. LBP was not influenced by limaprost, and a significant reduction of LBP and RDQ was confirmed in a combination treatment compared with limaprost. Physical function of the SF-36 subscales after a combination treatment showed a marked alleviation compared with NSAIDs. Conclusions: These obtained findings suggest that the effects of limaprost seem to be limited to radicular pain, not for LBP. Overall, a combination treatment might be more effective in the management of radiculopathy induced by LSS than monotherapy with either agent. [ABSTRACT FROM AUTHOR]

Introduction: Ileal duplications are encountered infrequently in adults, because symptoms including abdominal pain, intussusception, hemorrhage, and perforation usually present in early childhood. In this report, we present an adult case of ileal duplication that was revealed by double-balloon endoscopy (DBE). Case description: A 73-year-old Japanese man presented with anemia and melena. Anal DBE detected the narrow opening of an extra lumen in the ileum about 100 cm proximal to the ileocecal valve. Enteroclysis via DBE showed a 5-cm-long ileal diverticulum-like structure at the mesenteric side of the ileum. No ectopic gastric mucosa was detected by technetium-99m pertechnetate scintigraphy. The final diagnosis was ileal duplication. Discussion and evaluation: This is the first report of tubular ileal duplication diagnosed by using DBE. The small intestinal duplication opening was not detected by using VCE and plane CT in this case, but was found by using DBE. Conclusions: The present case demonstrates that DBE was useful in the diagnosis of an adult small intestinal duplication that was not visualized by other modalities. [ABSTRACT FROM AUTHOR]

Proton pump inhibitors (PPIs) alter the composition of the intestinal microbiome, exacerbating indomethacin (IND)-induced small intestinal damage. Vonoprazan fumarate inhibits gastric acid secretion using a different mechanism from PPIs. We investigated the effects of both drugs on the intestinal microbiome and IND-induced small intestinal damage. We sought to clarify whether PPI-induced dysbiosis and worsening of the damage were due to a specific drug class effect of PPIs. Rabeprazole administration increased operational taxonomic unit numbers in the small intestines of C57BL/6 J mice, whereas the difference was not significant in the vonoprazan-treated group but exhibited a trend. Permutational multivariate analysis of variance of the unweighted UniFrac distances showed significant differences between vehicle- and vonoprazan- or rabeprazole-treated groups. L. johnsonii was the predominant microbial species, and the population ratio decreased after vonoprazan and rabeprazole administration. The vonoprazan- and rabeprazole-treated groups showed increased IND-induced damage. This high sensitivity to IND-induced damage was evaluated by transplantation with contents from the small intestine of mice treated with either vonoprazan or rabeprazole. Supplementation of L. johnsonii orally in mice treated with rabeprazole and vonoprazan prevented the increase in IND-induced small intestinal damage. In conclusion, both rabeprazole and vonoprazan aggravated NSAID-induced small intestinal injury by reducing the population of L. johnsonii in the small intestine via suppressing gastric acid secretion. [ABSTRACT FROM AUTHOR]

The inflammasomes induce maturation of pro-interleukin-1β (IL-1β) and pro-IL-18. We investigated roles of the NLRP3 inflammasome in the pathogenesis of ulcerative colitis (UC). After induction of oxazolone-induced colitis, a mouse UC model, colonic tissues were assayed for inflammatory mediators. Histological studies were performed on inflamed colonic tissue from mice and UC patients. Histological severity of murine colitis peaked on day 1, accompanied by an increase in the expression of Th2 cytokines including IL-4 and IL-13. Oxazolone treatment stimulated maturation of pro-caspase-1 and pro-IL-1β, while it reduced IL-18 expression. Either exogenous IL-1β or IL-18 ameliorated the colitis with or without reduction in Th2 cytokine expression, respectively. Induction of colitis decreased MUC2 expression, which was reversed by administration of IL-18, but not IL-1β. Compared to wild-type mice, NLRP3−/− mice exhibited higher sensitivity to oxazolone treatment with enhancement of Th2 cytokine expression and reduction of mature IL-1β and IL-18 production; this phenotype was rescued by exogenous IL-1β or IL-18. Immunofluorescent studies revealed positive correlation of NLRP3 expression with disease severity in UC patients, and localization of the inflammasome-associated molecules in macrophages. The NLRP3 inflammasome-derived IL-1β and IL-18 may play a protective role against UC through different mechanisms. [ABSTRACT FROM AUTHOR]