Comorbid functional dyspepsia reflects IL-33-mediated airway neuronal dysfunction in asthma.

BACKGROUND: Neuronal dysfunction is implicated in the pathophysiology of asthma and functional dyspepsia (FD). However, the relationship between these diseases remains unclear. OBJECTIVE: This study aimed to clarify the clinical implications of comorbid FD in asthma and to explore the unified pathway between asthma and FD by focusing on airway neuronal dysfunction. METHODS: Clinical indices and biomarkers, including capsaicin cough sensitivity (C-CS), were compared between patients with asthma with and without FD. C-CS was determined on the basis of capsaicin concentration that induced at least 2 coughs (C2) or 5 coughs (C5). Additionally, the associations of airway inflammation with airway innervation and gastrointestinal motility were evaluated in mouse models of type 2 airway inflammation. RESULTS: Patients with asthma with FD had worse asthma control and cough severity and lower C2 and C5 thresholds than those without FD. The severity of FD symptoms was negatively correlated with C2 and C5 thresholds. FD and poor asthma control were predictors of heightened C-CS (defined as C5 ≤ 2.44 µmol) in asthma. A mouse model of papain-induced airway inflammation developed airway hyperinnervation and gastrointestinal dysmotility, and both pathologies were ameliorated by an anti-IL-33 antibody. Moreover, papain-induced gastrointestinal dysmotility was mitigated by silencing the airway sensory neurons using QX-314, a sodium channel blocker. Furthermore, sputum IL-33 levels were significantly elevated in patients with asthma with FD or heightened C-CS compared to their counterparts. CONCLUSION: FD is significantly associated with airway neuronal dysfunction in asthma. IL-33-mediated airway neuronal dysfunction may contribute to the interaction between asthma and FD.

Functional gastrointestinal disorders are associated with capsaicin cough sensitivity in severe asthma.

BACKGROUND: Although sensory nerve dysfunction is related to the pathology of severe uncontrolled asthma and functional gastrointestinal disorders (FGIDs), the impact of comorbid FGIDs on the pathophysiology of severe uncontrolled asthma remains poorly understood. The aim was to clarify the physiological relationships between severe uncontrolled asthma and FGIDs. METHODS: Fifty-two patients with severe uncontrolled asthma who visited our hospital between September 2016 and August 2019 were retrospectively analyzed. Clinical characteristics, other comorbidities including gastroesophageal reflux disease (GERD), and biomarkers such as fractional nitric oxide (FeNO) and capsaicin cough sensitivity (C-CS) before the beginning of biologics or bronchial thermoplasty, were compared between patients with and without comorbid FGIDs. C-CS was evaluated by C5 (concentration of inhaled capsaicin that induced five or more coughs), and C5 ≤2.44 µM was defined as heightened C-CS. RESULTS: Seventeen patients had comorbid FGIDs. These patients had a lower FeNO level (21.9 ± 1.7 ppb vs. 33.9 ± 2.8 ppb, P = 0.04), a lower C5 threshold (2.24 ± 2.88 µM vs. 8.91 ± 5.5 µM, P < 0.001), a higher prevalence of comorbid GERD (64.7% vs. 31.7%, P = 0.03), and a higher prevalence of heightened C-CS (70.6% vs. 28.6%, P = 0.007) than those without FGIDs. Analysis of covariance showed a significant effect of FGIDs on C-CS in severe uncontrolled asthma without being affected by GERD. CONCLUSIONS: Comorbid FGIDs are associated with heightened C-CS in patients with severe uncontrolled asthma, and they may be an important extra-respiratory manifestation of the airway neuronal dysfunction phenotype of severe uncontrolled asthma.

Causal effect of anxiety and depression status on the symptoms of gastroesophageal reflux disease and functional dyspepsia during proton pump inhibitor therapy.

BACKGROUND: Although anxiety and depression status is considered related to gastroesophageal reflux disease (GERD) and functional dyspepsia (FD) symptoms, ambiguity primarily arises from the difficulty in determining their cause-effect relationships. We aimed to examine the longitudinal reciprocal causation between anxiety/depression status and GERD/FD symptoms among symptomatic adult patients with GERD. METHODS: Adult (≥ 20 years) patients with GERD symptoms received PPI treatment for 4 weeks after endoscopy. GERD and FD symptom subscales (GERD-SS/FD-SS) were evaluated using the gastroesophageal reflux and dyspepsia therapeutic efficacy and satisfaction test (GERD-TEST). Anxiety and depression status were evaluated using the hospital anxiety and depression scale (HADS). A cross-lagged analysis using structural equation modeling was conducted to examine causal relationships among psychiatric bias (anxiety and depression scores) and upper gastrointestinal symptoms (GERD-SS and FD-SS scores) over time. RESULTS: A total of 182 patients with GERD (men: 120; age: 57.1 ± 12.8 years; body mass index: 24.2 ± 4.1 kg/m2; nonerosive reflux disease/erosive reflux disease: 61/121) were eligible before (T1) and after 4 weeks (T2) of PPI therapy. The cross-lagged effect model indicated that anxiety at T1 contributed to the FD-SS at T2 (ß = 0.18*) and depression at T1 contributed to the GERD-SS at T2 (ß = 0.23*) (*p < 0.05). CONCLUSION: Psychiatric bias was a risk factor for refractory GERD and FD. Anxiety and depression status reduced the therapeutic effect of PPIs on GERD and FD symptoms. Therefore, attention is required to detect the anxiety/depression status of patients with GERD/FD symptoms to treat patients appropriately and optimize therapeutic outcomes.

Effects of catheter-based renal denervation on heart failure with reduced ejection fraction: a meta-analysis of randomized controlled trials.

Despite the major progress in the treatment of heart failure, the burden of heart failure is steadily increasing in the Western world. Heart failure is characterized by increased sympathetic activity, and chronic sympathetic activation is involved in the maintenance of the pathological state. Recent studies have shown that catheter-based renal denervation (RDN) presents a safe and minimally invasive treatment option for uncontrolled hypertension, a condition that is driven by increased sympathetic activity. Although randomized controlled trials (RCTs) have examined the effect of RDN in heart failure patients, results are inconsistent due partly to limited power with small sample sizes. We aimed to conduct a meta-analysis of RCTs on the effect of RDN in heart failure patients with reduced left ventricular (LV) ejection fraction (EF). Electronic search identified 5 RCTs including 177 patients. In the pooled analysis, RDN increased LVEF (weighted mean difference (WMD) [95% CI] = 6.289 [1.883, 10.695]%) and 6-min walk distance (61.063 [24.313, 97.813] m) and decreased B-type natriuretic peptide levels (standardized mean difference [95% CI] = - 1.139 [- 1.824, - 0.454]) compared with control. In contrast, RDN did not significantly change estimated glomerular filtration rate (WMD [95% CI] = 5.969 [- 2.595, 14.533] ml/min/1.73 m2) and systolic (- 1.991 [- 15.639, 11.655] mmHg) or diastolic (- 0.003 [- 10.325, 10.320] mmHg) blood pressure compared with control. Our meta-analysis suggests that RDN may improve LV function and exercise capacity in heart failure patients with reduced EF, providing the rationale to conduct large-scale multicenter trials to confirm the observed potential benefits of RDN.

A Questionnaire-Based Survey on the Impact of the COVID-19 Pandemic on Gastrointestinal Endoscopy in Asia.

INTRODUCTION: The COVID-19 outbreak abruptly restricted gastrointestinal (GI) endoscopy services during the first wave of the pandemic. We aimed to assess the impact of COVID-19 on the practice of GI endoscopy in Asian countries. METHODS: This was an International Questionnaire-based Internet Survey conducted at multiple facilities by the International Gastrointestinal Consensus Symposium. A total of 166 respondents in Japan, China, Hong Kong, South Korea, Philippines, Thailand, Indonesia, and Singapore participated in this study. RESULTS: The volume of endoscopic screening or follow-up endoscopies and therapeutic endoscopies were markedly reduced during the first wave of the pandemic, which was mainly attributed to the decreased number of outpatients, cancellations by patients, and adherence to the guidelines of academic societies. The most common indications for GI endoscopy during the first wave were GI bleeding, cholangitis or obstructive jaundice, and a highly suspicious case of neoplasia. The most common GI symptoms of COVID-19 patients during the infected period included diarrhea, nausea, and vomiting. The pandemic exacerbated some GI diseases, such as functional dyspepsia and irritable bowel syndrome. There were cases with delayed diagnosis of cancers due to postponed endoscopic procedures, and the prescription of proton pump inhibitors/potassium-competitive acid blockers, steroids, immunosuppressive agents, and biologics was delayed or canceled. The personal protective equipment used during endoscopic procedures for high-risk patients were disposable gloves, disposable gowns, N95 or equivalent masks, and face shields. However, the devices on the patient side during endoscopic procedures included modified surgical masks, mouthpieces with filters, and disposable vinyl boxes or aerosol boxes covering the head. Furthermore, the time for education, basic research, clinical research, and daily clinical practice decreased during the first wave. CONCLUSION: This study demonstrated that the COVID-19 pandemic profoundly affected the method of performing GI endoscopy and medical treatment for patients with GI diseases in Asian countries.

Effect of renin-angiotensin system inhibition on cardiac structure and function and exercise capacity in heart failure with preserved ejection fraction: a meta-analysis of randomized controlled trials.

Targeting the renin-angiotensin system (RAS) pathways has been considered a logical intervention for patients with heart failure with preserved ejection fraction (HFpEF), due to its hypothesized link to left ventricular (LV) remodeling. Although the effects of RAS inhibitors including angiotensin-converting enzyme inhibitors (ACE-Is), angiotensin receptor blockers (ARBs), and direct renin inhibitors (DRIs) on LV structure and function and exercise capacity in HFpEF patients have been examined in multiple randomized controlled trials (RCTs), results are inconsistent due partly to limited power. We conducted a meta-analysis of RCTs on the effects of RAS inhibitors on LV structure and function as well as exercise capacity in HFpEF patients. The search of electronic databases identified 7 trials including 569 patients; 4 trials were on ACE-Is; 2 on ARBs; and 1 on DRIs. Follow-up duration ranged across trials from 12 to 52 weeks. The pooled analysis showed that RAS inhibitors significantly increased EF compared with control (weighted mean difference [95% CI] = 2.182 [0.462, 3.901] %). In contrast, RAS inhibitors did not significantly change the ratio of peak early to late diastolic mitral inflow velocities (weighted mean difference [95% CI] = 0.046 [- 0.012, 0.105]), early diastolic mitral annular velocity (0.327 [- 0.07, 0.725] cm/s), the ratio of early diastolic mitral inflow to annular velocities (0.291 [- 0.937, 1.518]), LV mass (- 6.254 [- 15.165, 2.656] g), or 6-min walk distance (1.972 [- 14.22, 18.163] m) compared with control. The present meta-analysis suggests that RAS inhibitors may increase LVEF in HFpEF patients.

Effect of beta-blockers on heart failure severity in patients with heart failure with preserved ejection fraction: a meta-analysis of randomized controlled trials.

Patients with heart failure with preserved ejection fraction (HFpEF) are often elderly and likely to have cardiac comorbidities such as coronary artery disease (CAD) and atrial fibrillation (AF). The primary chronic symptom of HFpEF patients is severe exercise intolerance. The inability to adequately increase heart rate during exercise is commonly present in HFpEF patients and contributes to their exercise intolerance. Although beta-blockers are frequently used for the treatment of myocardial ischemia and tachycardia in HFpEF patients, there is a concern that slowing heart rate by beta-blockers may worsen chronotropic incompetence and further exacerbate their symptoms. Although the effect of beta-blockers on heart failure severity in HFpEF patients has been examined in randomized controlled trials (RCTs), results are inconsistent due partly to limited power. We aimed to conduct a meta-analysis of RCTs on the effect of beta-blockers on heart failure severity in HFpEF patients. The search of electronic databases identified 5 RCTs including 538 patients. In pooled analyses, beta-blockers did not significantly change the New York Heart Association (NYHA) class, exercise capacity expressed as metabolic equivalents, or plasma B-type natriuretic peptide (BNP) levels compared with control but with substantial heterogeneity across trials. In meta-regression analyses, the higher proportion of CAD or AF in the included trials was associated with a decrease in NYHA class and BNP levels and with an increase in exercise capacity. Thus, we found no clear beneficial effect of beta-blockers on heart failure severity in HFpEF patients. However, beta-blockers may be beneficial in HFpEF patients with CAD or AF.

Sex differences in risk factors for future onset of reflux esophagitis.

Reflux esophagitis is known to be more prevalent in males, and previous studies have suggested sex differences in its risk factors. However, little is known about sex differences in the time-course of risk factors before reflux esophagitis onset. Thus, we conducted a retrospective longitudinal study using health checkup records. From the records of 230,056 individuals obtained from nine institutes in Japan, we selected 1,558 male reflux esophagitis cases, 3,116 male controls, 508 female reflux esophagitis cases, and 1,016 female controls were selected. We compared time-courses of risk factors between the case and control groups and identified abdominal circumference (AC), diastolic blood pressure, alanine transaminase (ALT), and current smoking in males and body mass index (BMI) in females as sex-specific risk factors. We also found that AC and ALT in males and BMI in females were significantly different between the reflux esophagitis case and control groups during the five years before reflux esophagitis onset. Our results suggest that visceral fat-type obesity and fatty liver in males and higher BMI in females are more frequently observed in reflux esophagitis cases several years before reflux esophagitis onset, and that proactive intervention to lifestyle can help prevent reflux esophagitis in both males and females.

The early therapeutic response at 2 weeks is a crucial predictor of proton pump inhibitor-refractory gastroesophageal reflux disease.

BACKGROUND: In recent years, the prevalence of proton pump inhibitor (PPI)-refractory gastroesophageal reflux disease (GERD) has been increasing, posing a clinical obstacle to improving the management of GERD patients. The ability of known predictive factors to explain therapeutic response to PPI remains insufficient. Therefore, we examined whether the addition of early therapeutic response to PPI as an explanatory variable may increase the predictive power for PPI-refractory GERD. METHODS: The severity and therapeutic response of GERD symptoms to PPI were evaluated using the GastroEsophageal Reflux and Dyspepsia Therapeutic Efficacy and Satisfaction Test (GERD-TEST) questionnaire at baseline and at 2 and 4 weeks after treatment. The relevance of the therapeutic effect of PPI at 2 weeks compared to that at 4 weeks was examined in 301 patients with GERD. Independent predictive factors for refractory GERD at 4 weeks of PPI therapy were examined in 182 patients. The effect of various clinical factors, including the early response to PPI, was assessed using multiple regression analysis. RESULTS: The number of PPI-therapy responders increased significantly with the duration of treatment (p < 0.0001). The response to PPI therapy at 2 weeks was significantly correlated with that at 4 weeks (p < 0.0001). Multiple regression analysis revealed that the therapeutic response to PPI at 2 weeks was by far the strongest predictor of the therapeutic effect at 4 weeks among all clinical factors. CONCLUSIONS: Medication change for PPI-refractory GERD at 2 weeks may be an efficacious therapeutic strategy to improve patients' quality of life.

Effect of anti-reflux treatment on gastroesophageal reflux-associated chronic cough: Implications of neurogenic and neutrophilic inflammation.

Objective: Gastroesophageal reflux disease (GERD) is an important cause of chronic cough. Substance P (SP) has been implicated in the pathophysiology of cough. Proton pump inhibitors (PPIs) and prokinetic agents are the current treatment for GER-associated cough. The aim was to evaluate the effects of anti-reflux treatment and its associations with cellular and neurogenic inflammation.Methods: Thirty-seven patients with GER-associated cough suspected based on characteristic symptoms such as heartburn and worsening of cough by phonation and rising were recruited. A PPI, rabeprazole 20 mg daily, and a prokinetic agent, itopride 50 mg t.i.d., were administered for 4 weeks in a prospective, observational manner. Before and after treatment, subjective cough measures [visual analog scale (VAS) and the Japanese version of the Leicester Cough Questionnaire (J-LCQ)], the modified frequency scale for the symptoms of GERD [FSSG, consisting of 2 domains: acid-reflux (AR) and functional dyspepsia symptoms], sputum and plasma SP levels, and sputum cell differentials were examined. Patients with good response to treatment [Δ (decrease of) VAS >15 mm; n = 21) were compared with poor responders (ΔVAS ≤15 mm).Results: Anti-reflux treatment significantly improved the cough VAS, J-LCQ, and AR symptoms, and ΔVAS and ΔAR were significantly correlated. Decreases of plasma and sputum SP levels and sputum neutrophil counts were significantly greater in responders than in poor responders. Both baseline values and post-treatment changes of plasma SP and sputum neutrophils were significantly correlated for all patients.Conclusions: Successful treatment of GER-associated cough may be associated with the attenuation of neurogenic and neutrophilic inflammation.

Questionnaire-Based Survey on Epidemiology of Functional Gastrointestinal Disorders and Current Status of Gastrointestinal Motility Testing in Asian Countries.

BACKGROUND/AIMS: Functional gastrointestinal disorders (FGIDs) are diagnosed and classified using the latest Rome IV criteria, released in 2016. Epidemiology of FGID diagnosed by the Rome IV criteria and current clinical application of gastrointestinal motility testing in Asian countries are not well known. The aims of this survey are to elucidate the present situation of epidemiology and diagnostic tests of FGID in clinical practice in some East and Southeast Asian countries. METHODS: The questionnaire focusing on current situation of FGID diagnosis and gastrointestinal motility testing was distributed to members of the International Gastroenterology Consensus Symposium study group and collected to be analyzed. RESULTS: The prevalence rates of subtypes of both functional dyspepsia (FD) and irritable bowel syndrome (IBS) are relatively similar in all Asian countries. In these countries, most patients underwent both upper endoscopy and Helicobacter pylori test to diagnose FD. Colonoscopy was also frequently performed to diagnose IBS and chronic constipation. The frequency of gastrointestinal motility testing to examine gastric emptying and colonic transit time varied among Asian countries. CONCLUSIONS: This survey revealed epidemiology of FGIDs and current status of gastrointestinal motility testing in some East and Southeast Asian countries.

Management of Gastroesophageal Reflux Disease in Asian Countries: Results of a Questionnaire Survey.

INTRODUCTION: The Asia-Pacific consensus on the management of gastroesophageal reflux disease (GERD) and the GERD treatment guidelines of 2015 drawn up by the Japanese Society of Gastroenterology were proposed, and GERD management in Asian regions was assumed to be performed based on these consensuses. In this environment, the current status of GERD management in clinical practice among Asian regions is less well-known. OBJECTIVE: This questionnaire-based consensus survey was performed to clarify the current status of management of GERD in clinical practice in Asian regions. METHODS: A questionnaire related to management of GERD was distributed to members of the International Gastroenterology Consensus Symposium Study Group. We analyzed the questionnaire responses and compared the results among groups. RESULTS: The frequencies of erosive GERD (ERD), non-ERD, uninvestigated GERD, and Barrett's esophagus varied significantly among Asian countries. The most important factor in diagnosing GERD was the presence of symptoms in all countries. A proton pump inhibitor was the most commonly prescribed drug to treat GERD in all countries. Endoscopic surveillance for GERD was performed regularly. CONCLUSION: This questionnaire survey revealed the current status of management of GERD in clinical practice in various Asian countries.

Comparison of Hemorrhagic Risk between Prasugrel and Clopidogrel: a Retrospective Study using Adverse Drug Event Reporting Databases.

Background: Prasugrel inhibits platelet aggregation more potently and exerts therapeutic action faster than clopidogrel. In the global phase III trial conducted in Western and South American countries that excluded Asian countries, prasugrel reduced ischemic events but increased hemorrhagic risk compared with clopidogrel in patients with acute coronary syndrome scheduled for percutaneous coronary intervention. In the Japanese phase III trial for similar patients, the efficacy of prasugrel compared with clopidogrel was comparable to the global trial, but the safety could not be confirmed because of an insufficient number of patients. Furthermore, given the strict enrollment criteria, the results of these trials may not be applicable to routine clinical practice. Accordingly, we compared the hemorrhagic risk of prasugrel and clopidogrel in real-world settings by analyzing adverse drug event reports in post-marketing stages provided by the Japanese regulatory authorities and the U.S. Food and Drug Administration (FDA). Methods: We analyzed a total of 3,970 reports for prasugrel (n = 518) or clopidogrel (n = 3,452) between 2014 and 2017 in the Japanese Adverse Drug Event Report (JADER) and a total of 91,914 reports for either prasugrel (n = 5,992) or clopidogrel (n = 85,922) between 2009 and 2019 in the FDA Adverse Event Reporting System (FAERS). Results: In JADER and FAERS, prasugrel was more frequently and significantly associated with hemorrhagic event reports than clopidogrel. After adjustment for known confounders including age, sex, and concomitant medications (aspirin, anticoagulants, and proton pump inhibitors), the hemorrhagic risk of prasugrel compared with clopidogrel remained significant (adjusted reporting odds ratios [95% CI] for total, intracranial, and gastrointestinal hemorrhagic events = 2.42 [1.97-2.96], 2.45 [1.85-3.24], and 2.27 [1.73-2.97] in JADER, and 2.21 [2.09-2.34], 1.21 [1.09-1.33], and 1.41 [1.29-1.54] in FAERS). Conclusions: The hemorrhagic risk was found to be greater with prasugrel than clopidogrel in real-world patients, including Japanese patients.

Effects of exercise training on cardiac function, exercise capacity, and quality of life in heart failure with preserved ejection fraction: a meta-analysis of randomized controlled trials.

Left ventricular (LV) diastolic dysfunction is associated with the pathophysiology of heart failure with preserved ejection fraction (HFpEF) and contributes importantly to exercise intolerance that results in a reduced quality of life (QOL) in HFpEF patients. Although the effects of exercise training on LV diastolic function, exercise capacity, or QOL in HFpEF patients have been examined in randomized clinical trials (RCTs), results are inconsistent due partly to limited power with small sample sizes. We aimed to conduct a meta-analysis of RCTs examining the effects of exercise training on LV diastolic function and exercise capacity as well as QOL in HFpEF patients. The search of electronic databases identified 8 RCTs with 436 patients. The duration of exercise training ranged from 12 to 24 weeks. In the pooled analysis, exercise training improved peak exercise oxygen uptake (weighted mean difference [95% CI], 1.660 [0.973, 2.348] ml/min/kg), 6-min walk distance (33.883 [12.384 55.381] m), and Minnesota Living With Heart Failure Questionnaire total score (9.059 [3.083, 15.035] point) compared with control. In contrast, exercise training did not significantly change early diastolic mitral annular velocity (weighted mean difference [95% CI], 0.317 [- 0.952, 1.587] cm/s), the ratio of early diastolic mitral inflow to annular velocities (- 1.203 [- 4.065, 1.658]), or LV ejection fraction (0.850 [- 0.128, 1.828] %) compared with control. In conclusion, the present meta-analysis suggests that exercise training improves exercise capacity and QOL without significant change in LV systolic or diastolic function in HFpEF patients.

The effect of influenza vaccination on mortality and hospitalization in patients with heart failure: a systematic review and meta-analysis.

Influenza infection is associated with increased risk for mortality and hospitalization in heart failure patients. Although there are no published randomized controlled trials examining the effect of influenza vaccination on clinical outcomes in heart failure patients, the effect has been examined in observational cohort studies. Nevertheless, results are inconsistent due partly to limited power with small sample sizes and use of different definitions of outcomes. We therefore aimed to conduct a systematic review and meta-analysis of the effect of influenza vaccination on mortality and hospitalization in heart failure patients. The search of electronic databases identified 6 observational cohort studies with 22,486 patients examining the effect of influenza vaccination on mortality and hospitalization in heart failure patients. Pooled analysis of confounder-adjusted hazard ratio showed that influenza vaccination was associated with reduced risk of mortality during 1-year follow-up (risk ratio [95% CI] = 0.76 [0.63-0.92], Pfix < 0.01) and during long-term (up to 4 years) follow-up (0.80 [0.71-0.90], Pfix < 0.001). Furthermore, influenza vaccination was associated with reduced risk of mortality during influenza season (risk ratio [95% CI] = 0.52 [0.39-0.69], Prandom < 0.001) and during non-influenza season (0.79 [0.69-0.90], Pfix < 0.001). Only a few studies reported the effect of influenza vaccination on hospitalization, which did not permit us to perform pooled analysis. In conclusion, our meta-analysis showed that influenza vaccination was associated with reduced risk of mortality in heart failure patients. Large-scale and adequately powered randomized controlled trials should be planned to confirm our observed potential survival benefit of influenza vaccination in these patients.

Questionnaire-Based Survey on Management of Ulcerative Colitis-Associated Cancer in East Asian Countries.

BACKGROUND/AIMS: To elucidate the current management of ulcerative colitis (UC)-associated cancer, a questionnaire-based survey was conducted to gather current opinions on colitis-associated cancer in different East Asian countries. METHODS: The questionnaire, based on physicians, contains 9 questions focused on UC management and cancer surveillance. In addition, the questionnaire based on neoplastic cases, which contains 17 questions, was collected and analyzed. RESULTS: With regard to the diagnosis of UC-associated cancer, most respondents started surveillance colonoscopy within 10 years from onset, favored targeted biopsies, and thought advanced imaging was useful. As for morphology, the frequency of elevated lesion and type 4 lesions was most common in early and advanced cancer, respectively. Peritoneal metastasis was frequently observed, and undifferentiated tumor was frequently developed. Laparoscopic surgery was widely used because it is less invasive. The prognostic outcome was poor, particularly in stage III and undifferentiated type. CONCLUSIONS: The current survey elucidated the current management in Asian countries and characteristics of colitis-associated cancer in these countries.

Effects of mineralocorticoid receptor antagonists on left ventricular diastolic function, exercise capacity, and quality of life in heart failure with preserved ejection fraction: a meta-analysis of randomized controlled trials.

Left ventricular (LV) diastolic dysfunction is associated with the pathophysiology of heart failure with preserved ejection fraction (HFpEF) and contributes importantly to exercise intolerance that results in a reduced quality of life (QOL) in HFpEF patients. Experimental studies have shown that aldosterone plays a role in the genesis of myocardial hypertrophy and fibrosis, thereby enhancing LV diastolic dysfunction, and that aldosterone antagonists (mineralocorticoid receptor antagonists [MRAs]) prevents myocardial hypertrophy and fibrosis. Although the effects of MRAs on LV diastolic function, exercise capacity, and QOL in HFpEF patients have been examined in randomized clinical trials (RCTs), results are inconsistent due partly to limited power with small sample sizes. We aimed to conduct a meta-analysis of RCTs on the effects of MRAs on LV diastolic function, exercise capacity, and QOL in HFpEF patients. The search of electronic databases identified 6 studies including 755 HFpEF patients. In the pooled analysis, MRAs increased early diastolic mitral annular velocity (weighted mean difference [95% CI] = 0.455 [0.232-0.679] cm/s; Pfix < 0.001) and decreased the ratio of early diastolic mitral inflow to annular velocities (- 1.474 [- 2.073 to - 0.875]; Pfix < 0.001) compared with control. There was no significant difference in change of peak exercise oxygen uptake, 6-minute walking distance, or QOL questionnaire scores between MRA and control group. In conclusion, our meta-analysis showed that MRAs improved LV diastolic function in HFpEF patients. However, the observed improvement in LV diastolic function with the use of MRAs did not translate into improved exercise capacity or QOL in these patients.

Sodium- and Potassium-Hydrate Melts Containing Asymmetric Imide Anions for High-Voltage Aqueous Batteries.

Aqueous Na- or K-ion batteries could virtually eliminate the safety and cost concerns raised from Li-ion batteries, but their widespread applications have generally suffered from narrow electrochemical potential window (ca. 1.23 V) of aqueous electrolytes that leads to low energy density. Herein, by exploring optimized eutectic systems of Na and K salts with asymmetric imide anions, we discovered, for the first time, room-temperature hydrate melts for Na and K systems, which are the second and third alkali metal hydrate melts reported since the first discovery of Li hydrate melt by our group in 2016. The newly discovered Na- and K- hydrate melts could significantly extend the potential window up to 2.7 and 2.5 V (at Pt electrode), respectively, owing to the merit that almost all water molecules participate in the Na+ or K+ hydration shells. As a proof-of-concept, a prototype Na3 V2 (PO4 )2 F3 |NaTi2 (PO4 )3 aqueous Na-ion full-cell with the Na-hydrate-melt electrolyte delivers an average discharge voltage of 1.75 V, that is among the highest value ever reported for all aqueous Na-ion batteries.

Questionnaire-Based Survey on Gastrointestinal Bleeding and Management of Antithrombotic Agents during Endoscopy Among Asian Countries.

OBJECTIVE: Guidelines on the management of antithrombotic therapy for endoscopic procedures vary among countries. Differences in the management of antithrombotic agents for endoscopic procedures between Western and Eastern countries have already been reported. However, no study has investigated the differences among Asian countries. The aim of this study was to examine the differences in the etiology of gastrointestinal bleeding and management of antithrombotic agents during endoscopic procedures between Japan and other Asian countries (OAC). METHODS: Questionnaires regarding gastrointestinal bleeding in clinical practice and management of antithrombotic agents during endoscopy were distributed to members of the International Gastroenterology Consensus Symposium Study Group. We analyzed the questionnaire answers and compared the results between Japan and OAC. RESULTS: The cause of and treatment methods for gastrointestinal bleeding differed between Japan and OAC. In Japan, the trend was to continue drugs at the time of biopsy and endoscopic therapy. Even in cases of discontinuation, the drug withdrawal period was as short as <3 days. Thrombotic complications caused by the withdrawal of antithrombotic agents were observed more frequently in Japan (34.78%) than in OAC (22.46%; p = 0.016). CONCLUSION: Due to differences in guidelines and complications associated with discontinuation of drugs, the antithrombotic withdrawal period in Japan tended to be shorter than that in OAC.

Asian Perspectives on Diagnostic and Therapeutic Strategies in Inflammatory Bowel Disease: Report and Analysis of a Survey with Questionnaires.

BACKGROUND: Diagnostic and therapeutic strategies in inflammatory bowel disease (IBD) vary among countries in terms of availability of modalities, affordability of health care resource, health care policy and cultural background. This may be the case in different countries in Eastern Asia. The aim of this study was to determine and understand the differences in diagnostic and therapeutic strategies of IBD between Japan and the rest of Asian countries (ROA). METHODS: Questionnaires with regard to clinical practice in IBD were distributed to members of the International Gastroenterology Consensus Symposium Study Group. The responders were allowed to select multiple items for each question, as multiple modalities are frequently utilized in the diagnosis and the management of IBD. Dependency and independency of selected items for each question were evaluated by the Bayesian network analysis. RESULTS: The selected diagnostic modalities were not very different between Japan and ROA, except for those related to small bowel investigations. Balloon-assisted enteroscopy and small bowel follow through are frequently used in Japan, while CT/MR enterography is popular in ROA. Therapeutic modalities for IBD depend on availability of such modalities in clinical practice. As far as modalities commonly available in both regions are concerned, there seemed to be similarity in the selection of each therapeutic modality. However, evaluation of dependency of separate therapeutic modalities by Bayesian network analysis disclosed some difference in therapeutic strategies between Japan and ROA. CONCLUSION: Although selected modalities showed some similarity, Bayesian network analysis elicited certain differences in the clinical approaches combining multiple modalities in various aspects of IBD between Japan and ROA.