Effects of beta-blocker withdrawal in patients with heart failure with preserved ejection fraction: A protocol for systematic review and meta-analysis.

BACKGROUND: The primary chronic symptom of patients with heart failure with preserved ejection fraction (HFpEF) is severe exercise intolerance. The inability to adequately increase heart rate during exercise (chronotropic incompetence) is commonly present in HFpEF patients and contributes importantly to exercise intolerance in these patients. Since HFpEF patients often have cardiac comorbidities such as hypertension, coronary artery disease, and atrial fibrillation, beta-blockers are frequently prescribed for the treatment of these comorbidities. However, there is a concern that beta-blockers may worsen chronotropic incompetence by slowing heart rate in HFpEF patients and may further exacerbate their symptoms. There are several studies on the effects of beta-blocker withdrawal in HFpEF patients. We aim to perform the systematic review and meta-analysis of studies on the effects of beta-blocker withdrawal in HFpEF patients. METHODS: This meta-analysis will include randomized controlled trials and prospective cohort studies on the effect of beta-blocker withdrawal in HFpEF patients. Information of studies will be collected from PubMed, Web of Science, and Scopus. The primary outcome will be peak oxygen uptake (peak VO2). The secondary outcome will be 6-minute walk distance. Other outcomes of interest will be health-related quality of life, plasma BNP levels, and cardiac structure and function. DISCUSSION: This systematic review and meta-analysis will evaluate whether beta-blocker withdrawal is beneficial for HFpEF patients, providing evidence regarding beta-blocker withdrawal in these patients. TRIAL REGISTRATION: Systematic review registration: INPLASY202370066.

Risk factors associated with overall survival in patients with multiple myeloma following carfilzomib treatment: A retrospective study from a large claims database in Japan.

BACKGROUND: Carfilzomib is a selective proteasome inhibitor approved for treating relapsed or refractory multiple myeloma (RRMM). Carfilzomib improves overall survival (OS) and progression-free survival (PFS); however, treatment with carfilzomib results in a higher incidence of cardiovascular and renal toxicity. More than 70% of patients with RRMM in clinical practice do not meet the eligibility criteria for randomized clinical trials (RCT). OS and PFS are negatively influenced by complications, concomitant medications and prior treatments. Therefore, we assessed the risk factors influencing the OS and time to next treatment (TTNT) in the real world. TTNT has emerged as a relevant alternative clinical endpoint to PFS. METHODS: A retrospective analysis of a large claims database prepared during the post-marketing stages in Japan was performed. The patients treated with carfilzomib for the first time were identified. Multivariable Cox proportional hazards regression analysis was performed to evaluate the risk factors influencing OS and TTNT following carfilzomib treatment. RESULTS: A total of 732 patients with RRMM who received carfilzomib-containing chemotherapy between April 2014 and September 2021 were identified. Multivariable Cox regression analysis for OS and TTNT showed a significantly higher hazard ratio (HR) of 1.48 (95% confidence interval [Cl]: 1.10-2.00; p = 0.010) and 1.38 (95% Cl: 1.15-1.65; p < 0.001), respectively, for patients with renal impairment compared to those without renal impairment. Multivariable Cox regression analysis for OS and TTNT showed a significantly higher HR of 1.80 (95% Cl: 1.27-2.55; p = 0.0010) and 1.38 (95% Cl: 1.14-1.66; p < 0.001), respectively, for patients with prior lenalidomide treatment compared to those without prior lenalidomide treatment. CONCLUSION: Complication of renal impairment and prior lenalidomide treatment could be risk factors influencing OS and TTNT during carfilzomib treatment.

Association of epicardial fat with cardiac structure and function and cardiovascular outcomes: A protocol for systematic review and meta-analysis.

BACKGROUND: Epicardial fat represents visceral adiposity. Many observational studies have reported that increased epicardial is associated with adverse metabolic profile, cardiovascular risk factors, and coronary atherosclerosis in patients with cardiovascular diseases and in general population. We and others have previously reported the association of increased epicardial fat with left ventricular (LV) hypertrophy and diastolic dysfunction as well as the development of heart failure (HF) and coronary artery disease in these populations. In some studies, however, the association did not reach statistical significance. The inconsistent results may be due to limited power, different imaging modalities for quantifying epicardial fat volume, and different outcome definitions. Accordingly, we aim to perform the systematic review and meta-analysis of studies on the association of epicardial fat with cardiac structure and function and cardiovascular outcomes. METHODS: This systematic review and meta-analysis will include observational studies examining the association of epicardial fat with cardiac structure and function or the cardiovascular outcomes. Relevant studies will be identified by searching electronic databases including PubMed, Web of Science, and Scopus and by manual screening of reference lists of relevant reviews and retrieved studies. The primary outcome will be cardiac structure and function. The secondary outcome will be cardiovascular events including death from cardiovascular causes, hospitalization for HF, nonfatal myocardial infarction, and unstable angina. DISCUSSION: The results of our systematic review and meta-analysis will provide evidence regarding the clinical usefulness of epicardial fat assessment. SYSTEMATIC REVIEW REGISTRATION: INPLASY 202280109.

Clinical characteristics and mortality risk among critically ill patients with COVID-19 owing to the B.1.617.2 (Delta) variant in Vietnam: A retrospective observational study.

BACKGROUND: SARS-CoV-2 Delta variant caused a large number of COVID-19 cases in many countries, including Vietnam. Understanding mortality risk factors is crucial for the clinical management of severe COVID-19. METHODS: We conducted a retrospective study at an intensive care center in Ho Chi Minh City that urgently built by Bach Mai Hospital during the COVID-19 outbreak in Vietnam, when the Delta variant predominated. Participants were laboratory-confirmed patients with SARS-CoV-2 infection, admitted in August 2021. Data on patients' demographic and clinical characteristics, radiographic and laboratory findings, treatment, and clinical time course were compared between survivors and non-survivors. Risk factors to mortality were assessed using logistic regression. RESULTS: Among 504 eligible COVID-19 patients, case fatality was 52.2%. Unvaccinated patients accounted for 61.2% of non-survivors and 43.6% of survivors (p < 0.001). The time from onset to hospital admission was 8 days in non-survivors and 7 days in survivors (p = 0.004). Among non-survivors, 90.2% developed acute respiratory distress syndrome (ARDS). Oxygen therapy was administered for all patients, but antiviral agent was given to 51.7% of non-survivors. 54.2% of non-survivors tested positive for the bacterial infection using blood culture. The risk factors for mortality were diabetes mellitus, respiration rate, oxygen saturation, vaccination status, time from onset to admission, and older age. CONCLUSIONS: Critical patients with COVID-19 owing to the Delta variant in Vietnam had delayed hospital admission, leading to ARDS and death. Early availability of vaccines and preventing bacterial infections are crucial for reducing mortality of COVID-19, especially in low- and middle-income countries.

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.

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.

Comparison of the effects of individual symptoms of gastroesophageal reflux disease co-existing functional dyspepsia on patients' daily lives: A prospective, observational study.

Background and Aim: Patients with gastroesophageal reflux disease (GERD) frequently also have functional dyspepsia (FD) symptoms, which impair their quality of life. However, the magnitude and characteristics of the effects of each symptom on daily life have been unclarified. Using multiple regression analysis, we aimed to clarify these questions. Methods: We enrolled 290 patients from 29 institutions across Japan, in this prospective, observational study. Patients responded to three questionnaires (Gastroesophageal Reflux and Dyspepsia Therapeutic Efficacy and Satisfaction Test [GERD-TEST], Hospital Anxiety and Depression Scale [HADS], and 8-item Short-Form Health Survey [SF-8]) before and after 4 weeks of proton pump inhibitor treatment. Pearson correlation and multiple regression analyses were conducted between symptoms such as typical GERD, epigastric pain syndrome (EPS) and postprandial distress syndrome (PDS) of FD, and aspects of daily life, namely, level of satisfaction with the daily life of GERD-TEST, anxiety and depression score of HADS, and physical and mental component summary of SF-8. Results: Pearson correlation analysis showed a significant correlation in all combinations between GERD/FD-EPS/FD-PDS symptoms and the nine aspects of daily life. However, multiple regression analysis results deviated from these results, with the most significant effects seen in the PDS-symptom subscale (SS) on the five aspects of daily life, that is, dissatisfaction with eating, daily life-SS, anxiety, depression, and mental component summary (MCS) whereas the significant effects in GERD-SS on five aspects of daily life, that is, dissatisfaction for eating, anxiety, depression, physical component summary, and MCS, disappeared. Conclusion: Dealing with co-existing FD symptoms without overlooking them may be important in the management of GERD.

Spinterface Effects in Hybrid La0.7Sr0.3MnO3/SrTiO3/C60/Co Magnetic Tunnel Junctions.

Orbital hybridization at the Co/C60 interface been has proved to strongly enhance the magnetic anisotropy of the cobalt layer, promoting such hybrid systems as appealing components for sensing and memory devices. Correspondingly, the same hybridization induces substantial variations in the ability of the Co/C60 interface to support spin-polarized currents and can bring out a spin-filtering effect. The knowledge of the effects at both sides allows for a better and more complete understanding of interfacial physics. In this paper we investigate the Co/C60 bilayer in the role of a spin-polarized electrode in the La0.7Sr0.3MnO3/SrTiO3/C60/Co configuration, thus substituting the bare Co electrode in the well-known La0.7Sr0.3MnO3/SrTiO3/Co magnetic tunnel junction. The study revealed that the spin polarization (SP) of the tunneling currents escaping from the Co/C60 electrode is generally negative: i.e., inverted with respect to the expected SP of the Co electrode. The observed sign of the spin polarization was confirmed via DFT calculations by considering the hybridization between cobalt and molecular orbitals.

Clinical significance of gastroesophageal reflux disease with minimal change: a multicenter prospective observational study.

Non-erosive reflux disease (NERD) is classified into grade N (no minimal change) and grade M (minimal change) based on the Los Angeles classification. However, few reports have described the clinical characteristics of grade M. This study was performed to clarify the clinical characteristics of grade M. Among 290 consecutive patients with gastroesophageal reflux disease (GERD), 45 patients with grade M, 62 patients with grade N, and 94 patients with grade A were compared with respect to clinical differences. The degree of symptom improvement after 4 weeks of proton pump inhibitor administration was also prospectively compared among the three groups. Grades N and M showed no or little difference in the patients' backgrounds (including sex and body mass index), GERD/functional dyspepsia symptom scores, life dissatisfaction (diet, sleep, work, and mood), Short Form-8 (mental component summary) scores, and symptom improvement. In contrast, significant differences were present between grades M and A as well as between grades N and A. The overall results of our study suggest that the distinction between grade M and grade N is of little clinical significance from the viewpoint of clinical characteristics.

Hypoxia-inducible factor prolyl hydroxylase inhibitors for anemia in heart failure patients: A protocol for systematic review and meta-analysis.

BACKGROUND: Anemia is common in heart failure (HF) patients with chronic kidney disease (CKD) and is associated with worse outcomes. Iron supplementation improves symptoms and is associated with reduced risk of hospitalization for HF in iron-deficiency HF patients. However, iron deficiency is present in <30% of anemic HF patients. Erythropoiesis stimulating agents (ESAs) improve symptoms but are associated with increased risk of thromboembolic events in anemic HF patients with CKD. Hypoxia-inducible factor prolyl hydroxylase (HIF-PH) inhibitors are a new class of agents for the treatment of anemia. These agents work by stabilizing the HIF complex, thereby stimulating endogenous erythropoietin production. We hypothesized that HIF-PH inhibitors may be associated with reduced risk of cardiovascular outcomes compared with ESAs in anemic HF patients with CKD. Accordingly, we aim to perform the meta-analysis of studies on the efficacy and safety of HIF-PH inhibitors compared with ESAs in anemic HF patients with CKD. METHODS: This meta-analysis will include prospective cohort studies and randomized controlled trials on the effect of HIF-PH inhibitors compared with ESAs in anemic HF patients with CKD. Information of studies will be collected from PubMed, Web of Science, Cochrane Library, and ClinicalTrials.gov. The primary outcome will be cardiovascular death. The secondary outcomes will be all-cause death, hospitalization for HF, HF symptoms, exercise capacity, health-related quality of life, and hemoglobin levels. DISCUSSION: This meta-analysis will evaluate the effect of HIF-PH inhibitors in anemic HF patients with CKD, providing evidence regarding the use of HIF-PH inhibitors in these patients. SYSTEMATIC REVIEW REGISTRATION: INPLASY202230103.

Sodium-glucose cotransporter 2 inhibitors in heart failure with preserved ejection fraction: A meta-analysis of randomized controlled trials.

Background: Nearly half of patients with heart failure (HF) have preserved ejection fraction (EF) and the mortality and morbidity of patients with HF with preserved EF (HFpEF) are high. Patients with HFpEF are often elderly and their primary chronic symptom is severe exercise intolerance that results in a reduced quality of life. Thus, improvement of exercise capacity and quality of life presents another important clinical outcome in HFpEF patients. Recent randomized controlled trials (RCTs) and meta-analyses of RCTs reported that sodium-glucose cotransporter 2 (SGLT-2) inhibitors improved cardiovascular (CV) outcomes in patients with HF with reduced EF. Although the effects of SGLT-2 inhibitors in HFpEF patients have been examined in multiple RCTs, results are inconsistent due partly to limited power. We aimed to conduct a meta-analysis of RCTs on the effects of SGLT-2 inhibitors in HFpEF patients. Methods and Results: The search of electronic databases identified 11 RCTs including 10,845 patients. In pooled analyses, SGLT-2 inhibitors reduced the risk of a composite of hospitalization for HF and CV death (hazard ratio [95 % CI] = 0.78 [0.70, 0.87], Pfix < 0.001). SGLT-2 inhibitors significantly increased 6-minute walk distance (weighted mean difference [95 % CI] = 18.0 [6.8, 29.3] m; Pfix = 0.002) and the Kansas City Cardiomyopathy Questionnaire Total Symptom Score (weighted mean difference [95 % CI] = 2.57 [0.19, 4.96] points; Prandom = 0.035) and reduced plasma NT-pro B-type natriuretic peptide levels (weighted mean difference [95 % CI] = -60.16 [-82.99, -37.33] pg/ml; Pfix < 0.001) compared with control. Conclusion: The present meta-analysis suggests that SGLT-2 inhibitors may be beneficial for HFpEF patients, especially in diabetic patients.

Influenza vaccination in patients with heart failure: A protocol for meta-analysis of randomized controlled trials.

BACKGROUND: Heart failure is a major public health problem. Although there have been significant advances in the management of heart failure, the mortality and morbidity in heart failure patients remain high. Heart failure patients are susceptible to influenza-related complications including acute heart failure exacerbations and secondary infections such as pneumonia, both of which lead to significant morbidity and mortality. An earlier meta-analysis of observational cohort studies reported that influenza vaccination was associated with reduced risk of mortality in heart failure patients. Although there are no published randomized controlled trials (RCTs) on the effect of influenza vaccination on clinical outcomes in heart failure patients, there are several on-going RCTs examining the effect in these patients. We aim to conduct a meta-analysis of RCTs to assess the efficacy and safety of influenza vaccination in heart failure patients. METHODS: This meta-analysis will include RCTs examining the effect of influenza vaccination in heart failure patients. Information of studies will be collected from electronic databases. The primary outcome of interest will be cardiovascular death. The secondary outcomes of interest will be all-cause death, nonfatal myocardial infarction, nonfatal stroke, hospitalization for heart failure, and hospitalization for any cause. DISCUSSION: This meta-analysis will evaluate the efficacy and safety of influenza vaccination in heart failure patients, providing evidence to the use of influenza vaccine in these patients. SYSTEMATIC REVIEW REGISTRATION: INPLASY202210115.

Disturbed gastric motility in patients with long-standing diabetes mellitus.

PURPOSE: Gastric dysmotility has been reported in patients with long-standing diabetes mellitus (DM). Some patients with DM are diagnosed as diabetes gastroparesis and have several upper gastrointestinal (GI) symptoms such as appetite loss and abdominal pain. This study aimed to identify the relationship between gastric motility and upper GI symptoms in patients with long-standing DM. METHOD: This study was conducted among 23 patients with DM and 15 healthy controls. All the patients with DM were receiving insulin treatment and had at least one history of incidence of diabetic nephropathy, retinopathy or neuropathy. Gastric motility was evaluated using electrogastrography (EGG) and gastric emptying using the 13C-acetic acid breath test. The most severe upper gastrointestinal symptoms were assessed in all patients. RESULTS: Compared to healthy controls, patients with long-standing DM showed a significantly lower percentage of normogastria at the postprandial state with a lower power ratio in EGG. Gastric emptying was significantly delayed in patients with DM in the overall analysis. Sixteen patients with DM (69.6%) demonstrated abnormalities in either gastric myoelectrical activity or gastric emptying. Among patients with abnormal EGG or delayed gastric emptying, 12 had some GI symptoms, compared with 3 patients with normal gastric motility. No significant correlation was observed between the gastric emptying parameters and HbA1c values. CONCLUSION: Patients with long-standing DM showed gastric dysmotility, including impaired gastric myoelectrical activity and delayed gastric emptying. Gastric dysmotility appears to be closely correlated with upper GI symptoms in patients with long-standing DM.

Predictive Factors for Future Onset of Reflux Esophagitis: A Longitudinal Case-control Study Using Health Checkup Records.

BACKGROUND/AIMS: Although risk factors of reflux esophagitis (RE) have been investigated in numerous cross-sectional studies, little is known about predictive factors associated with future onset of RE. We investigated time courses of clinical parameters before RE onset by a longitudinal case-control study using health checkup records. METHODS: We used health checkup records between April 2004 and March 2014 at 9 institutions in Japan. A multivariate logistic regression analysis was performed to evaluate associations of baseline clinical parameters with RE. The time courses of the clinical parameters of RE subjects were compared with those of non-RE subjects by the mixed-effects models for repeated measures analysis or longitudinal multivariate logistic analysis. RESULTS: Initial data were obtained from 230 056 individuals, and 2066 RE subjects and 4132 non-RE subjects were finally included in the analysis. Body mass index, alanine aminotransferase, smoking, acid reflux symptoms, hiatal hernia, and absence of atrophic gastritis at baseline were independently associated with RE. The time courses of body mass index, fasting blood sugar, triglyceride, aspartate aminotransferase, alanine aminotransferase, γ-glutamyl transpeptidase, percentages of acid reflux symptoms, feeling of fullness, and hiatal hernia in the RE group were significantly worse than in the non-RE group. CONCLUSIONS: The RE group displayed a greater worsening of the clinical parameters associated with lifestyle diseases, including obesity, diabetes, hyperlipidemia, and fatty liver for 5 years before RE onset compared with the non-RE group. These results suggest that RE is a lifestyle disease and thus lifestyle guidance to at-risk person may help to prevent RE onset.

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.

Sodium-glucose cotransporter 2 inhibitors in heart failure with preserved ejection fraction: A protocol for meta-analysis.

BACKGROUND: Nearly half of patients with heart failure (HF) have preserved ejection fraction (EF) and the mortality and morbidity of patients with HF with preserved EF (HFpEF) are high. Patients with HFpEF are often elderly and their primary chronic symptom is severe exercise intolerance that results in a reduced quality of life. Thus, improvement of exercise capacity presents another important clinical outcome in HFpEF patients. Recent randomized controlled trials (RCTs) and meta-analyses of RCTs reported that sodium-glucose cotransporter 2 (SGLT-2) inhibitors improved cardiovascular outcomes in patients with HF with reduced EF. Although the effects of SGLT-2 inhibitors in HFpEF patients have been examined in multiple RCTs, the results are inconsistent due partly to limited power. The purpose of this meta-analysis is to evaluate the efficacy and safety of SGLT-2 inhibitors in HFpEF patients. METHODS: This meta-analysis will include RCTs examining the effects of SGLT-2 inhibitors on HF severity and health-related quality of life in HFpEF patients. Information of studies will be collected from electronic databases. The primary outcome will be HF severity (plasma B-type natriuretic peptide levels and exercise capacity assessed as 6-minute walk distance). The secondary outcome will be health-related quality of life. The safety outcomes will be all-cause death, HF hospitalization, hypotension, acute renal failure, diabetic ketoacidosis, and urinary tract infection. DISCUSSION: This meta-analysis will evaluate the efficacy and safety of SGLT-2 inhibitors in HFpEF patients, providing evidence to the clinical use of SGLT-2 inhibitors in these patients. SYSTEMATIC REVIEW REGISTRATION: INPLASY2021120033.

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.

Iron therapy in iron-deficiency patients with heart failure with preserved ejection fraction: A protocol for meta-analysis.

BACKGROUND: Nearly half of patients with heart failure (HF) have preserved ejection fraction (EF) and the mortality and morbidity of patients with HF with preserved EF (HFpEF) are high. However, there is no established therapy to improve survival in these patients. HFpEF patients are often elderly and their primary chronic symptom is severe exercise intolerance. Thus, improvement of exercise capacity presents another important clinical outcome in HFpEF patients. Iron deficiency is common in HF patients, and the presence of iron deficiency, regardless of concomitant anemia, is associated with worse symptoms, impaired exercise capacity, and higher mortality and hospitalization in these patients. Several meta-analyses of randomized controlled trials reported that iron administration improved HF symptoms, exercise capacity, and clinical outcomes in iron-deficiency patients with HF with reduced EF. However, there is insufficient evidence as to the effect of iron administration in iron-deficiency HFpEF patients. METHODS AND RESULTS: This meta-analysis will include randomized controlled trials on the effects of iron administration on HF symptoms, exercise capacity, and health-related quality of life in iron-deficiency HFpEF patients. Information of studies will be collected from PubMed, Web of Science, Cochrane Library, and ClinicalTrials.gov. The primary outcome will be exercise capacity (6-minute walking distance). The secondary outcomes will be HF symptoms, health-related quality of life, and mortality and hospitalization rates. CONCLUSION: This meta-analysis will evaluate the effect of iron therapy in iron-deficiency HFpEF patients, providing evidence as to the iron administration in these patients. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42020205297.