ORCID Profile
0000-0002-7937-3699
Current Organisations
Royal Children's Hospital
,
Nationwide Children's Hospital
,
Keio University
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Publisher: Authorea, Inc.
Date: 18-11-2020
DOI: 10.22541/AU.160571540.02057981/V1
Abstract: Background: Multisystem inflammatory syndrome in children (MIS-C) associated with COVID-19 has been increasingly recognized. However, the clinical features of MIS-C and the differences from Kawasaki disease remain unknown. The study aims to investigate the epidemiology and clinical course of MIS-C. Methods: PubMed and EMBASE were searched through August 30, 2020. Observational studies describing MIS-C were included. Data regarding demographic features, clinical symptoms, laboratory, echocardiography and radiology findings, treatments, and outcomes were extracted. Study-specific estimates were combined using one-group meta-analysis in a random-effects model. Results: A total of 27 studies were identified including 917 MIS-C patients. The mean age was 9.3 (95% confidence interval [CI], 8.4-10.1). The pooled proportions of Hispanic and Black cases were 34.6% (95% CI, 28.3-40.9) and 31.5% (95% CI, 24.8-38.1), respectively. The common manifestations were gastrointestinal symptoms (87.3% 95% CI, 82.9-91.6) and cardiovascular involvement such as myocardial dysfunction (55.3% 95% CI, 42.4-68.2), coronary artery aneurysms (21.7% 95% CI, 12.8-30.1) and shock (65.8% 95% CI, 51.1-80.4), with marked elevated inflammatory and cardiac markers. The majority of patients received intravenous immunoglobulin (81.0% 95% CI, 75.0-86.9), aspirin (67.3% 95% CI, 48.8-85.7), and corticosteroids (63.6% 95% CI, 53.4-73.8) with a variety of anti-inflammatory agents. Although myocardial dysfunction improved in 55.1% (95% CI, 33.4-76.8) at discharge, the rate of extracorporeal membrane oxygenation use was 6.3% (95% CI, 2.8-9.8) and the mortality was 1.9% (95% CI, 1.0-2.8). Conclusion: Our findings suggest that MIS-C leads to multiple organ failure, including gastrointestinal manifestations, myocardial dysfunction and coronary abnormalities, and has distinct features from Kawasaki disease.
Publisher: Wiley
Date: 11-01-2021
DOI: 10.1002/PPUL.25245
Publisher: American Medical Association (AMA)
Date: 2023
DOI: 10.1001/JAMAPEDIATRICS.2022.4768
Abstract: Published data on COVID-19 mRNA vaccine–associated myopericarditis in adolescents and young adults have been derived from small case series, national population-based studies, or passive reporting systems. Pooled evidence from a larger, international cohort is scarce. To investigate the clinical features and early outcomes associated with myopericarditis after COVID-19 mRNA vaccination in a heterogeneous population of adolescents and young adults. PubMed and EMBASE were searched through August 2022. Language restrictions were not applied. Observational studies and case series describing COVID-19 vaccine–associated myopericarditis in adolescents and young adults aged 12 to 20 years and reporting clinical characteristics and early outcomes were included. Two independent investigators extracted relevant data from each study. One-group meta-analysis in a random effects model was performed. The Preferred Reporting Items for Systematic Reviews and Meta-analysis and Meta-analysis of Observational Studies in Epidemiology reporting guidelines were followed. The primary outcomes were clinical features and early outcomes for COVID-19 mRNA vaccine–associated myopericarditis, including incident rate, cardiac findings, hospitalization, intensive care unit (ICU) admission, and in-hospital mortality. A total of 23 observational studies were identified, including 854 in iduals (mean age, 15.9 [95% CI, 15.5-16.2] years) with COVID-19 vaccine–associated myopericarditis. Male sex was predominant, at 90.3% (95% CI, 87.3%-93.2%) of in iduals. The incident rate was higher after the second dose than the first dose, with 74.4% (95% CI, 58.2%-90.5%) of events occurring after the second dose. Most patients (84.4% [95% CI, 80.5%-88.3%] of patients) had preserved left ventricular (LV) function. Of the 15.6% (95% CI, 11.7%-19.5%) of patients with LV systolic dysfunction (LV ejection fraction [LVEF] & %), most (14.1% [95% CI, 10.2%-18.1%]) were mild (ie, LVEF 45%-54%), and only 1.3% (95% CI, 0%-2.6%) of patients had severe LV systolic dysfunction (ie, LVEF& %). Interestingly, cardiac magnetic resonance imaging revealed late gadolinium enhancement in 87.2% (95% CI, 79.8%-94.7%) of patients. Although 92.6% (95% CI, 87.8%-97.3%) of patients were hospitalized and 23.2% (95% CI, 11.7%-34.7%) of patients required ICU admission, inotropes were used in only 1.3% (95% CI, 0%-2.7%) of patients, no patients died or required mechanical support, and the hospital length of stay was 2.8 (95% CI, 2.1-3.5) days. This systematic review and meta-analysis found low incidence rate and largely favorable early outcomes of COVID-19 mRNA vaccine–associated myopericarditis in adolescents and young adults from a wide range of populations. These findings are reassuring but continued follow-up is warranted.
Publisher: AME Publishing Company
Date: 09-2021
DOI: 10.21037/TP-21-297
Publisher: International Heart Journal (Japanese Heart Journal)
Date: 2015
DOI: 10.1536/IHJ.14-351
Abstract: Pulmonary arterial hypertension (PAH) is a common postoperative complication in patients with congenital heart disease (CHD). Although the recent clinical classification of pulmonary hypertension ided PAH associated with CHD (PAH-CHD) into several subclasses, the anatomical and hemodynamic features of postoperative PAH-CHD vary enormously. Therefore, it is still difficult to obtain clinical evidence supporting the indication of pulmonary vasodilators for PAH-CHD. We often encounter patients with PAH occurring after surgical treatment of tetralogy of Fallot (TOF), especially patients with major aortopulmonary collateral arteries (MAPCAs). PAH might be caused by pulmonary agenesis, hypoplasia and/or thrombosis, inadequate closure of the ventricular septal defect, relief of the pulmonic stenosis, or an excessively large prior systemic-to-pulmonary shunt. Moreover, patients with TOF and MAPCAs who are diagnosed as inoperable because of the presence of PAH show similar hemodynamic and clinical features to patients with Eisenmenger syndrome. The MAPCAs in these patients usually show hypoplastic and abnormal arborization. Based on our experience, we believe that PAH-targeted therapies are effective in some patients with PAH occurring after surgical treatment of TOF and MAPCAs, especially as an adjunct to percutaneous pulmonary angioplasty. To help classify patients with PAH associated with TOF, especially with MAPCAs, we propose several new subclassifications: "PAH due to hypoplastic pulmonary arterial beds", "PAH due to abnormal pulmonary arborization", or "segmental PAH associated with CHD." A multicenter registry of patients using a unified protocol is essential to explore the indications and efficacy of pulmonary vasodilators for postoperative PAH-CHD.
Publisher: Wiley
Date: 04-08-2020
DOI: 10.1002/PPUL.24991
Abstract: Limited pediatric cases with coronavirus disease 2019 (COVID‐19) have been reported and the clinical profiles regarding COVID‐19 in children remain obscure. Our aim was to investigate the clinical characteristics of COVID‐19 in children. PUBMED and EMBASE were searched through 20 June 2020, for case reports and case series reporting pediatric COVID‐19 cases. Epidemiological, clinical, laboratory, and radiological data were collected and analyzed to compare by age. Our search identified 46 eligible case reports and case series. A total of 114 pediatric cases with COVID‐19 were included. The main clinical features were mild symptoms including fever (64%), cough (35%), and rhinorrhea (16%), or no symptoms (15%). Ground‐like opacities were common radiological findings (54%). The main laboratory findings were lymphopenia (33%) and elevated D‐dimer (52%) and C‐reactive protein (40%) levels. We identified 17 patients (15%) with multisystem inflammatory syndrome in children (MIS‐C) manifesting with symptoms overlapping with, but distinct from, Kawasaki disease, including gastrointestinal symptoms, left ventricular systolic dysfunction, shock, and marked elevated inflammatory biomarkers. Twelve percent of the patients including 65% of the MIS‐C cases required intensive care because of hypotension. No deaths were reported. This systematic review found that children with COVID‐19 are generally less severe or asymptomatic. However, infants might be seriously ill and older children might develop MIS‐C with severe illness. Early detection of children with mild symptoms or an asymptomatic state and early diagnosis of MIS‐C are mandatory for the management of COVID‐19 and the prevention of transmission and a severe inflammatory state.
Publisher: Cold Spring Harbor Laboratory
Date: 09-12-2019
Publisher: Wiley
Date: 04-2014
DOI: 10.1111/PED.12268
Abstract: Primary ciliary dyskinesia (PCD) is a genetic disease that causes abnormalities in ciliary structure and/or function. Ciliated cells line the upper and lower respiratory tracts and the Eustachian tube. Impairment of mucus clearance at these sites leads to sinusitis, repeated pulmonary infections, bronchiectasis, and chronic otitis media. Situs inversus occurs randomly in approximately 50% of subjects with PCD. The triad of situs inversus, bronchiectasis and sinusitis is known as Kartagener syndrome. PCD is usually an autosomal recessive disease, but occasional instances of X-linked transmission have been reported. Specific diagnosis requires examination of ciliary function or structure on light and electron microscopy. Early diagnosis and respiratory management are important in order to prevent the development of bronchiectasis and deterioration in lung function. We report early diagnosis of PCD on nasal mucosal biopsy in two newborns who presented with prolonged respiratory distress and rhinorrhea.
Publisher: Elsevier BV
Date: 07-2022
DOI: 10.1016/J.EJVS.2022.03.044
Abstract: The newly proposed Global Limb Anatomic Staging System (GLASS), a categorical staging of infrainguinal artery disease complexity, is expected to correlate with clinical outcomes in patients with chronic limb threatening ischaemia (CLTI). This study aimed to verify the relationship between GLASS stages and clinical outcomes after endovascular treatment (EVT) and bypass surgery (BS). MEDLINE, Web of Science Core Collection, and Google Scholar were searched in consultation with a health sciences librarian through June 2021. This systematic review and meta-analysis was carried out according to the PRISMA guidelines. All studies comparing the outcomes of patients with CLTI stratified by GLASS staging were eligible. Amputation free survival (AFS), limb salvage rate (LSR), major adverse limb event (MALE), overall survival, immediate technical failure (ITF), and limb based patency (LBP) were analysed. Data were pooled and synthesised with a random effects model. Datasets from seven retrospective cohort studies and one randomised control trial with a total of 2 204 patients (2 483 limbs) were identified. Pooled estimates demonstrated statistical differences between GLASS 1+2 and GLASS 3 in LSR (HR 0.61 95% CI 0.47 - 0.80, p < .001) and MALE (HR 0.66 95% CI 0.53 - 0.83, p < .001). After stratification, there were statistical differences in AFS, LSR, and MALE between GLASS 1+2 and GLASS 3 in the EVT subgroup but not in BS. In GLASS 2 and 3, MALE was significantly worse after EVT. In GLASS stages 1, 2, and 3, ITF after EVT was 3.9%, 5.3%, and 27.9%, respectively. LBP after EVT was significantly different between GLASS 1+2 and GLASS 3 (HR 0.83 95% CI 0.71 - 0.97, p = .020). GLASS is predictive of LSR and MALE as well as ITF and LBP after EVT. The current meta-analysis suggests advanced GLASS stages favour BS over EVT.
Publisher: Springer Science and Business Media LLC
Date: 03-06-2020
Publisher: Elsevier BV
Date: 03-2016
Publisher: International Heart Journal (Japanese Heart Journal)
Date: 30-11-2019
DOI: 10.1536/IHJ.19-099
Abstract: Postoperative arrhythmias are a frequent and fatal complication after the Fontan operation. However, clinical evidence demonstrating early postoperative arrhythmias in children undergoing the Fontan operation is limited. This study aimed to evaluate the prevalence of arrhythmias and identify the predictors of early postoperative supraventricular tachyarrhythmias (SVTs) after the Fontan procedure.Data were analyzed from 80 pediatric patients who underwent Fontan procedures between April 2000 and December 2017 in a single-center retrospective study. Early postoperative SVTs were defined as arrhythmias within 30 days after the Fontan procedure. We ided the patients into two groups, with or without early postoperative arrhythmias, and the predictors of early postoperative arrhythmias were analyzed. A multivariate logistic regression analysis was performed to determine independent predictors of early postoperative SVTs after the Fontan procedure.Early postoperative SVTs were observed in 21 patients (26.3%). The most common arrhythmia was junctional ectopic tachycardia. After an adjustment, an atrioventricular valve regurgitation (AVVR) grade of ≥2 (odds ratio 10.54, 95% confidence interval 2.52 to 44.17, P = 0.001) and preoperative arrhythmias (odds ratio 26.49, 95% confidence interval 1.64 to 428.62, P = 0.021) were significant predictors of early postoperative SVTs after the Fontan operation.An AVVR grade ≥2 and preoperative arrhythmia were significant predictors associated with early postoperative SVTs. Intervention for AVVR may provide clinical benefit for preventing early postoperative arrhythmias after the Fontan operation.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 03-01-2023
DOI: 10.1097/SLA.0000000000005793
Abstract: The aim was to analyze the risk of progression to chronic limb-threatening ischemia (CLTI), utation and subsequent interventions after revascularization versus noninvasive therapy in patients with intermittent claudication (IC). Conflicting evidence exists regarding adverse limb outcomes after each treatment strategy. Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed. MEDLINE, Web of Science, and Google Scholar were searched aided by a health sciences librarian through August 16, 2022. Randomized control trials (RCTs) comparing invasive (endovascular or surgical revascularization) and noninvasive treatment (exercise and/or medical treatment) were included. PROSPERO registration was completed (CRD42022352831). A total of 9 RCTs comprising 1477 patients (invasive, 765 patients noninvasive, 712 patients) were eligible. During a mean of 3.6-year follow-up, progression to CLTI after invasive [5 (2–8) per 1000 person-years] and noninvasive treatment [6 (3–10) per 1000 person-years] were not statistically different [rate ratio (RR): 0.77 95% CI, 0.35–1.69 P =0.51, I 2 =0%]. Incidence of utation (RR: 1.69 95% CI, 0.54–5.26 P =0.36, I 2 =0%) and all-cause mortality (hazard ratio: 1.26 95% CI, 0.91–1.74 P =0.16, I 2 =0%) also did not differ between the groups. However, the invasive treatment group underwent significantly more revascularizations (RR: 4.15 95% CI, 2.80–6.16 P .00001, I 2 =83%). The results were not changed by fixed effect or random-effects models, nor by sensitivity analysis. Although there is equivalent risk of progression to CLTI, major utation and all-cause mortality compared with noninvasive treatment, invasive treatment for patients with IC led to significantly more revascularization procedures and should be used selectively in patients with major lifestyle limitation. Guideline recommendation of noninvasive treatment for first-line IC therapy is supported.
Publisher: Elsevier BV
Date: 10-2016
Publisher: Cold Spring Harbor Laboratory
Date: 23-01-2022
DOI: 10.1101/2022.01.23.22269214
Abstract: The COVID-19 pandemic has a major impact on a global scale. Understanding the innate and lifestyle-related factors influencing the rate and severity of COVID-19 is important for making evidence-based recommendations. This cross-sectional study aimed at establishing a potential relationship between human characteristics and vulnerability/resistance to SARS-CoV-2. We hypothesize that the impact of virus is not the same due to cultural and ethnic differences. A cross-sectional study was performed using an online questionnaire. The methodology included a development of a multi-language survey, expert evaluation and data analysis. Data was collected using a 13-item pre-tested questionnaire based on a literature review. Data was statistically analyzed using the logistic regression. For a total of 1125 respondents, 332 (29.5%) were COVID-19 positive, among them 130 (11.5%) required home-based treatment, and 14 (1.2%) intensive care. The significant factors included age, physical activity and health status all found to have a significant influence on the infection (p 0.05). The severity of infection was associated with preventive measures and tobacco (p 0.05). This suggests the importance of behavioral factors compared to innate ones. Apparently, the in idual behavior is mainly responsible for the spread of the virus. Adopting a healthy lifestyle and scrupulously observing preventive measures including vaccination would greatly limit the probability of infection and prevent the development of severe COVID-19.
Publisher: Elsevier BV
Date: 09-2015
DOI: 10.1016/J.AMJCARD.2015.06.020
Abstract: The red blood cell distribution width (RDW) is a quantitative measure of the variability in the size of circulating erythrocytes. We aimed to study whether higher levels of the RDW were associated with heart failure in a Fontan circulation and to analyze its clinical value compared to brain natriuretic peptide. This retrospective study included 38 consecutive pediatric patients with a Fontan circulation who underwent routine cardiac catheterization at the International Medical Center, Saitama Medical University from October 2010 to July 2014. We assessed the relation between the RDW and catheterization data such as the central venous pressure (CVP), mixed venous oxygen saturation (SvO2), and cardiac index (CI). The RDW was positively correlated with the CVP (p = 0.0002). The elevated RDW group had a significantly greater CVP than the normal RDW group (p = 0.0003). Also, the RDW was negatively correlated with the SvO2 (p = 0.0004). The elevated RDW group had a significantly less SvO2 than the normal RDW group (p <0.0001). The CI in the elevated RDW group was lower than that in the normal RDW group (p = 0.0421). In the multivariate regression analysis, the RDW was a significant independent predictor of the CVP and SvO2. The BNP level did not have any significant relation with the CVP, SvO2, or CI. The RDW is a convenient and powerful marker for detecting heart failure in a Fontan circulation.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 15-02-2019
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 30-01-2023
Publisher: SAGE Publications
Date: 20-12-2021
DOI: 10.1177/1358863X211061603
Abstract: Background: Pharmacotherapy for undersized abdominal aortic aneurysm (AAA) is a clinical unmet need. Randomized controlled trials (RCTs) have failed to show effectiveness despite countless promising data in preclinical studies. We aimed to identify the population with undersized AAAs (30–54 mm) who potentially benefit from pharmacotherapy. Methods: In accordance with the PRISMA statement, we conducted a systematic review and meta-analysis of placebo-controlled RCTs. The primary outcome was mean difference (MD) in annual growth rate ( 0 favors pharmacotherapy), and the secondary outcome was aneurysm-related events (diameters ⩾ 55 mm, ruptures, or referral to surgery). Results: Our search strategy identified eight RCTs (six trials on antibiotics [ABx], two on renin-angiotensin system inhibitors [RAS-I]) with a total of 1325 patients. The mean of baseline diameters ranged from 33.1 mm to 43.1 mm. Neither ABx nor RAS-I showed significant differences in MD. Multivariable random-effects restricted maximum likelihood meta-regression revealed a statistically significant linear relationship between baseline diameter and MD (coefficient 0.15 [95% CI 0.0011, 0.30], p = 0.049) but not for the follow-up period ( p = 0.28) and duration of treatment ( p = 0.11). In line with this result, ABx with baseline diameter 40 mm significantly reduced MD (−1.03 mm/year [95% CI −1.64, −0.42], p = 0.001) and a borderline significant difference in aneurysm-related events (HR 0.53 [95% CI 0.28, 1.00], p = 0.05), whereas the other groups ⩾ 40 mm never demonstrated effectiveness. Fixed-effect models did not change the results. No evidence of publication bias was detected. Conclusion: Undersized AAAs 40 mm can potentially benefit from pharmacotherapy. Future RCTs should consider preferentially including undersized AAA with smaller diameters.
Publisher: Elsevier BV
Date: 07-2022
DOI: 10.1016/J.EJVS.2022.05.005
Abstract: To clarify the natural history of abdominal aortic ectasia (AAE) measuring 25 - 29 mm in maximum diameter, and to determine the optimal follow up based on the growth, risk of rupture, and overall mortality of AAE. MEDLINE, Web of Science Core Collection, and Google Scholar. This was a systematic review and meta-analysis of AAE in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. MEDLINE, Web of Science Core Collection, and Google Scholar were searched, with the help of a health sciences librarian, up to 11 August 2021. Studies with longitudinal outcomes of AAE (prevalence, annual growth rate, aneurysmal enlargement, rupture, aneurysm related death, and all cause mortality) were included. Meta-analyses were conducted with a random effects model RESULTS: Twelve studies describing a total of 8 369 patients were eligible. The prevalence at population based settings was 3.2% (95% confidence interval [CI] 2.4 - 4.0) annual growth rate was 0.82 mm/year (95% CI 0.20 - 1.45). The estimated risks of aortic diameters exceeding 30 mm and 55 mm in five years were 45.0% (95% CI 28.5 - 61.5) and 0.3% (95% CI 0 - 0.6) respectively, while those beyond five years were 70.2% (95% CI 46.9 - 93.6) and 5.2% (95% CI 2.2 - 8.2). The rates of rupture and aneurysm related death were minimal until five years (0.1% and 0.1%, respectively) and beyond (0.4% and 0.2%, respectively). Overall mortality was 7.5% (95% CI 3.9 - 11.0) and 17.3% (95% CI 9.5 - 25.1) up to and beyond five years. Overall mortality from three studies showed no statistical difference between AAE and aneurysms (hazard ratio 0.62, 95% CI 0.32 - 1.21 p = .16). Cancer (35.0%) and cardiovascular diseases (31.9%) were major causes of death. AAE carries minimal risk of aneurysm related lethal events during the first five years, but a similar overall mortality risk as abdominal aortic aneurysm. Cancer and cardiovascular diseases are leading causes of death in patients with AAE.
Publisher: Elsevier BV
Date: 2022
DOI: 10.1016/J.JVS.2021.07.240
Abstract: Controversy has continued regarding the use of endovascular aneurysm repair (EVAR) vs open aneurysm repair (OAR) for infected abdominal aortic aneurysms (AAAs). In the present study, we investigated the comparative outcomes of EVAR and OAR for the treatment of infected AAAs. We conducted a systematic review and meta-analysis using the MEDLINE and EMBASE databases through May 2021. We included studies that had described both EVAR and OAR for the treatment of infected AAAs. The primary endpoints were the rates of recurrent infection and related rupture and/or death. Perioperative and 1-year mortality and readmissions and reinterventions were also analyzed. Fourteen observational studies describing a total of 1203 patients (EVAR, 359 [29.8%] OAR, 844 [70.2%]) were eligible for qualitative analysis. The baseline characteristics included diabetes mellitus (33.2%), fever at presentation (71.6%), rupture at diagnosis (26.1%), and positive blood cultures (52.5%). The mean follow-up period ranged from 12 to 40 months. The use of EVAR became more prevalent in recent years (2016-2020, 32.4%) compared with the former period (2010-2015, 13.8% P < .0001). Fenestrated, branched, or concomitant visceral debranching EVAR was performed in 6.1% of cases. In OAR, surgical debridement was consistently performed, and in situ reconstruction was applied in 82.2% and an omental flap in 51.5%. In nine studies considered for quantitative analysis, the patients' background (EVAR, n = 264 OAR, n = 274) were statistically balanced. The crude rates of recurrent infection and related rupture or death were 13.6% (95% confidence interval [CI], 8.8%-18.5%) and 4.9% (95% CI 1.8%-8.0%), respectively. The pooled analyses depicted significantly higher rates of recurrent infection after EVAR than after OAR (relative risk [RR], 2.42 95% CI, 1.80-3.27 P < .0001 I EVAR has become more prevalent as the initial treatment of infected AAAs. Although operative and 1-year survival were similar between OAR and EVAR groups, recurrent infection was more frequent after EVAR. This limitation should be weighed in selecting patients for EVAR in infected AAAs. Postoperative graft and infection surveillance are critical, especially after EVAR.
Publisher: Elsevier BV
Date: 2019
Publisher: Cambridge University Press (CUP)
Date: 02-2023
DOI: 10.1017/S1047951123000124
Abstract: The optimal treatment strategy using pulmonary vasodilators in pulmonary arterial hypertension associated with CHD (PAH-CHD) remains controversial. We aimed to compare the efficacy and safety of pulmonary vasodilators in PAH-CHD. PubMed and EMBASE databases were searched through May 2022 and a network meta-analysis was conducted. The primary outcomes were mean difference of changes in 6-minute walk distance, NYHA functional class, and N-terminal pro-brain natriuretic peptide. The secondary outcomes included pulmonary vascular resistance, mean pulmonary arterial pressure, and resting oxygen saturation. We identified 14 studies, yielding 807 patients with PAH-CHD. Bosentan and sildenafil were associated with a significant increase in 6-minute walk distance from baseline compared with placebo (MD 48.92 m, 95% CI 0.32 to 97.55 and MD 59.70 m, 95% CI 0.88 to 118.53, respectively). Bosentan, sildenafil, and combination of bosentan and sildenafil were associated with significant improvement in NYHA functional class compared with placebo (MD −0.33, 95% CI −0.51 to −0.14, MD −0.58, 95% CI −0.75 to −0.22 and MD −0.62, 95% CI −0.92 to −0.31, respectively). Bosentan and sildenafil were also associated with significant improvements in secondary outcomes. These findings were largely confirmed in the subgroup analysis. Various adverse events were reported however, serious adverse event rates were relatively low (4.8–8.7%), including right heart failure, acute kidney injury, respiratory failure, hypotension, and discontinuation of pulmonary vasodilators. In conclusion, bosentan and sildenafil were the most effective in improving prognostic risk factor such as 6-minute walk distance and NYHA class. Overall, pulmonary vasodilators were well tolerated in PAH-CHD.
Publisher: Elsevier BV
Date: 05-2018
DOI: 10.1016/J.CJCA.2018.02.008
Abstract: Patients with Mulibrey nanism (MUL) present with growth failure and multiple organ manifestations, and MUL is caused by mutations in TRIM37. In this article, we report on the first case series of Japanese patients with MUL who developed congestive heart failure due to constrictive pericarditis. Our case series suggests that early diagnosis and total pericardiectomy before adherence of the pericardium might provide clinical benefit and better prognosis for MUL.
Publisher: Elsevier BV
Date: 09-2022
Publisher: The Company of Biologists
Date: 2019
DOI: 10.1242/DMM.036764
Abstract: Congenital heart defects affect ∼2% of live births and often involve malformations of the semilunar (aortic and pulmonic) valves. We previously reported a highly penetrant GATA4 p.Gly296Ser mutation in familial, congenital atrial septal defects and pulmonic valve stenosis and showed that mice harboring the orthologous G295S disease-causing mutation display not only atrial septal defects, but also semilunar valve stenosis. Here, we aimed to characterize the role of Gata4 in semilunar valve development and stenosis using the Gata4G295Ski/wt mouse model. GATA4 is highly expressed in developing valve endothelial and interstitial cells. Echocardiographic examination of Gata4G295Ski/wt mice at 2 months and 1 year of age identified functional semilunar valve stenosis predominantly affecting the aortic valve, consistent with the distal leaflet thickening and severe extracellular matrix (ECM) disorganization. Examination of the aortic valve at earlier postnatal timepoints demonstrated similar ECM abnormalities consistent with congenital disease. Analysis at embryonic timepoints showed a reduction in aortic valve cushion volume at embryonic day (E) 13.5, predominantly affecting the non-coronary cusp (NCC). While total cusp volume recovered by E15.5, the NCC cusp remained statistically smaller. As endothelial to mesenchymal transition (EMT)-derived cells contribute significantly to the NCC, we performed proximal outflow tract cushion explant assays and found EMT deficits in Gata4G295Ski/wt embryos along with deficits in cell proliferation. RNA-seq analysis of E15.5 outflow tracts of mutant embryos suggested a disease state and identified changes in genes involved in ECM and cell migration as well as dysregulation of Wnt signaling. By utilizing a mouse model harboring a human disease-causing mutation, we demonstrate a novel role for GATA4 in congenital semilunar valve stenosis.
Publisher: Springer Singapore
Date: 2020
Publisher: American Medical Association (AMA)
Date: 03-2023
Publisher: Springer Science and Business Media LLC
Date: 22-11-2023
Publisher: American Medical Association (AMA)
Date: 11-2022
DOI: 10.1001/JAMAPEDIATRICS.2022.3456
Abstract: The risk and benefits of COVID-19 vaccination during pregnancy are under investigation. Pooled evidence regarding neonatal and maternal outcomes in association with COVID-19 vaccination during pregnancy is scarce. To evaluate the association between COVID-19 vaccination during pregnancy and peripartum outcomes. PubMed and EMBASE databases were searched on April 5, 2022. Language restrictions were not applied. Prospective trials and observational studies comparing the in iduals who received at least 1 COVID-19 vaccination during pregnancy with those who did not and reporting the neonatal outcomes, including preterm birth, small for gestational age, low Apgar score, neonatal intensive care units (NICU) admission, and intrauterine fetal death (IFD). Two independent investigators extracted relevant data from each study. Odds ratios (ORs) were calculated using a random-effects model. This study followed the Preferred Reporting Items for Systematic Reviews and Meta-analysis guidelines. The primary outcomes were the neonatal outcomes, including preterm birth, small for gestational age, low Apgar score, NICU admission, and IFD. The secondary outcomes were maternal outcomes, including maternal SARS-CoV-2 infection, cesarean delivery, postpartum hemorrhage, and chorioamnionitis. Nine observational studies involving 81 349 vaccinated (mean age, 32-35 years) and 255 346 unvaccinated in iduals during pregnancy (mean age, 29.5-33 years) were included. COVID-19 vaccination during pregnancy was associated with lower risk of NICU admission (OR, 0.88 95% CI, 0.80-0.97) and IFD (OR, 0.73 95% CI, 0.57-0.94), whereas there was no statistically significant association with preterm birth (OR, 0.89 95% CI, 0.76-1.04), small for gestational age (OR, 0.99 95% CI, 0.94-1.04), and low Apgar score (OR, 0.94 95% CI, 0.87-1.02). COVID-19 vaccination during pregnancy was associated with a lower risk of maternal SARS-CoV-2 infection (OR, 0.46 95% CI, 0.22-0.93), whereas it was not associated with increased risk of cesarean delivery (OR, 1.05 95% CI, 0.93-1.20), postpartum hemorrhage (OR, 0.95 95% CI, 0.83-1.07), and chorioamnionitis (OR, 1.06 95% CI, 0.86-1.31). COVID-19 vaccination during pregnancy was not associated with an increase in the risk of peripartum outcomes, was associated with a decreased risk of NICU admission, IFD, and maternal SARS-CoV-2 infection. Thus, COVID-19 vaccination should be encouraged for pregnant in iduals.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 17-11-2022
DOI: 10.1097/PCC.0000000000003113
Abstract: The indication, complications, and outcomes of extracorporeal membrane oxygenation (ECMO) in children with COVID-19–related illnesses remain unelucidated. Our study aimed to investigate the characteristics and outcomes of ECMO in children with COVID-19–related illnesses. We searched PubMed and EMBASE databases in March 2022. We retrieved all studies involving children (age ≤ 18 yr) with COVID-19–related illnesses who received ECMO. Two authors independently extracted data and assessed the risk of bias. Mortality, successful weaning rate, and complications while on ECMO were synthesized by a one-group meta-analysis using a random-effect model. Meta-regression was performed to explore the risk factors for mortality. We included 18 observational studies, four case series, and 22 case reports involving 110 children with COVID-19–related illnesses receiving ECMO. The median age was 8 years (range, 10 d to 18 yr), and the median body mass index was 21.4 kg/m 2 (range, 12.3–56.0 kg/m 2 ). The most common comorbidities were obesity (11% [7/63]) and congenital heart disease (11% [7/63]), whereas 48% (30/63) were previously healthy. The most common indications for ECMO were multisystem inflammatory syndrome in children (52% [47/90]) and severe acute respiratory distress syndrome (40% [36/90]). Seventy-one percent (56/79) received venoarterial-ECMO. The median ECMO runtime was 6 days (range, 3–51 d) for venoarterial ECMO and 11 days (range, 3–71 d) for venovenous ECMO. The mortality was 26.6% (95% CI, 15.9–40.9), and the successful weaning rate was 77.0% (95% CI, 55.4–90.1). Complications were seen in 37.0% (95% CI, 23.1–53.5) while on ECMO, including stroke, acute kidney injury, pulmonary edema, and thromboembolism. Corticosteroids and IV immunoglobulin therapies were associated with lower mortality. The mortality of children on ECMO for COVID-19 was relatively low. This invasive treatment can be considered as a treatment option for critically ill children with COVID-19.
Publisher: American Medical Association (AMA)
Date: 04-2023
DOI: 10.1001/JAMAPEDIATRICS.2022.6243
Abstract: Evidence of the efficacy and safety of messenger RNA (mRNA) COVID-19 vaccines in children aged 5 to 11 years has been emerging. Collecting these data will inform clinicians, families, and policy makers. To evaluate the efficacy and safety of mRNA COVID-19 vaccines in children aged 5 to 11 years in a systematic review and meta-analysis. PubMed and Embase databases were searched on September 29, 2022, without language restrictions. Randomized clinical trials and observational studies comparing vaccinated vs unvaccinated children aged 5 to 11 years and reporting efficacy or safety outcomes were included. Studies reporting safety outcomes in vaccinated children only (ie, no control group) were also included. Two investigators independently extracted relevant data from each study. Odds ratios (ORs) for efficacy and safety outcomes and incidences of adverse events (AEs) following vaccination were synthesized using a random-effects model. This study followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses and Meta-analysis of Observational Studies in Epidemiology reporting guidelines. The primary outcome was SARS-CoV-2 infections with or without symptoms. The secondary outcomes included symptomatic SARS-CoV-2 infections, hospitalizations, and multisystem inflammatory syndrome in children. The incidences of each AE following vaccination were also evaluated. Two randomized clinical trials and 15 observational studies involving 10 935 541 vaccinated children (median or mean age range, 8.0-9.5 years) and 2 635 251 unvaccinated children (median or mean age range, 7.0-9.5 years) were included. Two-dose mRNA COVID-19 vaccination compared with no vaccination was associated with lower risks of SARS-CoV-2 infections with or without symptoms (OR, 0.47 95% CI, 0.35-0.64), symptomatic SARS-CoV-2 infections (OR, 0.53 95% CI, 0.41-0.70), hospitalizations (OR, 0.32 95% CI, 0.15-0.68), and multisystem inflammatory syndrome in children (OR, 0.05 95% CI, 0.02-0.10). Two randomized clinical trials and 5 observational studies investigated AEs among vaccinated children. Most vaccinated children experienced at least 1 local AE following the first injection (32 494 of 55 959 [86.3%]) and second injection (28 135 of 46 447 [86.3%]). Vaccination was associated with a higher risk of any AEs compared with placebo (OR, 1.92 95% CI, 1.26-2.91). The incidence of AEs that prevented normal daily activities was 8.8% (95% CI, 5.4%-14.2%) and that of myocarditis was estimated to be 1.8 per million (95% CI, 0.000%-0.001%) following the second injection. In this systematic review and meta-analysis, COVID-19 mRNA vaccines among children aged 5 to 11 years were associated with measures of efficacy in preventing SARS-CoV-2 infection and severe COVID-19–related illnesses. While most children developed local AEs, severe AEs were rare, and most of AEs resolved within several days. These data provide evidence for future recommendations.
No related grants have been discovered for Jun Yasuhara.