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Objective: To investigate the possible impact of thrombin on soluble Fms-like tyrosine kinase 1 (sFlt-1) expression in trophoblasts. Design: Experimental. Setting: University hospital laboratory. Interventions(s): A trophoblast cell line (HRT-8/SVneo) was treated with thrombin, protease-activated receptor 1 (PAR-1)-specific agonist SFLLERN, and thrombin antagonist PPACK. Main Outcome Measure(s): mRNA expression of sFlt-1, vascular endothelial growth factor (VEGF), and placental growth factor (PlGF) in trophoblasts, with the use of real-time polymerase chain reaction; and the secretion of sFlt-1, VEGF, and PlGF protein from trophoblasts, with the use of ELISA. Result(s): Administration of thrombin (10 U/mL) and PAR-1-specific agonist SFLLRN (300 μmol/L) increased sFlt-1 mRNA expression (4.24 ± 0.74- and 4.21 ± 0.79-fold, respectively) and protein secretion (5.08 ± 0.42- and 1.89 ± 0.16-fold, respectively) in HRT-8/SVneo. The induction of sFlt-1 protein secretion by thrombin was dose dependent. The effect of thrombin was completely reduced by thrombin inhibitor PPACK. Thrombin increased mRNA expression of VEGF but did not change VEGF secretion and PlGF mRNA expression and secretion. Conclusion(s): During placental development, thrombin, generated in the local hemorrhage of the uteroplacenta increases trophoblast expression of sFlt-1. Consequently, thrombin may contribute to the pathogenesis of preeclampsia. [ABSTRACT FROM AUTHOR]

Background: Ectopic pregnancy (EP) can be treated surgically or nonsurgically. In many countries, methotrexate is frequently used as a first-line medical treatment, and its effect is similar to that of surgery in selected patients. We aimed to investigate national trends in the treatment of EP in Japan., Methods: We conducted a retrospective observational analysis between 2010 and 2020 using a nationwide claims database that included inpatient data. We identified female inpatients with EP aged 15 to 49 years old. We analysed year-to-year treatment trends for EP, as well as year-to-year trends in methotrexate administration, with a focus on the site of the pregnancy. Patients who received methotrexate were divided into two groups: Those with and those without surgery after methotrexate use. We compared the characteristics of these groups and calculated the methotrexate success rate., Results: We identified 53,653 patients with EP. The proportion of patients undergoing surgery increased from 79% in 2010 to 83% in 2020, whereas the proportion of methotrexate therapy decreased from 8.1% in 2010 to 5.1% in 2020. Regarding methotrexate use for the site of the pregnancy, there was a significant downward trend in methotrexate therapy for tubal pregnancies. Notably, the methotrexate success rate was 84% during the study period., Conclusions: Surgery showed an increasing tendency over time, whereas methotrexate therapy showed a decreasing tendency for EP treatment in Japan. The efficacy of methotrexate in Japan was comparable to that observed in other countries.

Background: Asymptomatic premature ventricular complex (PVC) in childhood often disappears over time. However, predictive factors for persistent PVC are unknown. We examined predictive factors for persistent PVCs on initial Holter electrocardiogram (ECG) in pediatric patients with asymptomatic PVC.Methods and Results: The initial Holter ECG findings of untreated PVC patients (n=216) between 2010 and 2021 were examined. Multivariable analysis was performed to clarify predictive factors for subsequent persistent PVC burden for each index (age, sex, PVC burden, PVC origin, minimum and maximum mean RR intervals [RRmin and RRmax, respectively]) of the 3 heartbeats of baseline sinus rhythm immediately before the PVC. The median age at initial Holter ECG was 11.6 years (range 5.8-18.8 years), the PVC burden was 5.22% (range 0.01-44.21%), RRmin was 660 ms, RRmax was 936 ms, RRrange (=RRmax-RRmin) was 273 ms, and 15 (7%) PVC runs were identified. The median follow-up period was 5.1 years (range 0.8-9.4 years), and the final Holter PVC burden was 3.99% (range 0-36.38%). In multivariate analysis, RRrange was the only independent risk factor for predicting a final Holter PVC burden >10%, with an area under the curve of 0.920 using an RRrange of 600 ms as the cut-off value., Conclusions: A wide RRrange at the initial Holter ECG may be a predictive indicator for persistent PVC in childhood.

Aim: In April 2020, the Japanese government introduced a Specific Medical Fee for managing secondary dysmenorrhea (SD). This initiative provided financial incentives to medical facilities that provide appropriate management of SD with hormonal therapies. We aimed to assess how this policy affects the management processes and outcomes of patients with SD., Methods: Using a large Japanese administrative claims database, we identified outpatient visits of patients diagnosed with SD from April 2018 to March 2022. We used an interrupted time-series analysis and defined before April 2020 as the pre-introduction period and after April 2020 as the post-introduction period. Outcomes were the monthly proportions of outpatient visits due to SD and hormonal therapy among women in the database and the proportions of outpatient visits for hormonal therapy and continuous outpatient visits among patients with SD., Results: We identified 815 477 outpatient visits of patients diagnosed with SD during the pre-introduction period and 920 183 outpatient visits during the post-introduction period. There were significant upward slope changes after the introduction of financial incentives in the outpatient visits due to SD (+0.29% yearly; 95% confidence interval, +0.20% to +0.38%) and hormonal therapies (+0.038% yearly; 95% confidence interval, +0.030% to +0.045%) among the women in the database. Similarly, a significant level change was observed after the introduction of continuous outpatient visits among patients with SD (+2.68% monthly; 95% confidence interval, +0.87% to +4.49%)., Conclusions: Government-issued financial incentives were associated with an increase in the number of patients diagnosed with SD, hormonal therapies, and continuous outpatient visits., (© 2024 The Authors. Journal of Obstetrics and Gynaecology Research published by John Wiley & Sons Australia, Ltd on behalf of Japan Society of Obstetrics and Gynecology.)

Background: Allergic asthma is driven largely by allergen-specific T H 2 cells, which develop in regional lymph nodes on the interaction of naive CD4 + T cells with allergen-bearing dendritic cells that migrate from the lung. This migration event is dependent on CCR7 and its chemokine ligand, CCL21. However, is has been unclear whether the other CCR7 ligand, CCL19, has a role in allergic airway disease., Objective: This study sought to define the role of CCL19 in T H 2 differentiation and allergic airway disease., Methods: Ccl19-deficient mice were studied in an animal model of allergic asthma. Dendritic cells or fibroblastic reticular cells from wild-type and Ccl19-deficient mice were cultured with naive CD4 + T cells, and cytokine production was measured by ELISA. Recombinant CCL19 was added to CD4 + T-cell cultures, and gene expression was assessed by RNA-sequencing and quantitative PCR. Transcription factor activation was assessed by flow cytometry., Results: Lungs of Ccl19-deficient mice had less allergic airway inflammation, reduced airway hyperresponsiveness, and less IL-4 and IL-13 production compared with lungs of Ccl19-sufficient animals. Naive CD4 + T cells cocultured with Ccl19-deficient dendritic cells or fibroblastic reticular cells produced lower amounts of type 2 cytokines than did T cells cocultured with their wild-type counterparts. Recombinant CCL19 increased phosphorylation of STAT5 and induced expression of genes associated with T H 2 cell and IL-2 signaling pathways., Conclusions: These results reveal a novel, T H 2 cell-inducing function of CCL19 in allergic airway disease and suggest that strategies to block this pathway might help to reduce the incidence or severity of allergic asthma., (Copyright © 2023. Published by Elsevier Inc.)

Background: Cardiac calmodulinopathy, characterized by a life-threatening arrhythmia and sudden death in the young, is extremely rare and caused by genes encoding calmodulin, namely calmodulin 1 (CALM1), CALM2, and CALM3., Methods and results: We screened 195 symptomatic children (age 0-12 years) who were suspected of inherited arrhythmias for 48 candidate genes, using a next-generation sequencer. Ten probands were identified as carrying variants in any of CALM1-3 (5%; median age 5 years), who were initially diagnosed with long QT syndrome (LQTS; n=5), catecholaminergic polymorphic ventricular tachycardia (CPVT; n=3), and overlap syndrome (n=2). Two probands harbored a CALM1 variant and 8 probands harbored 6 CALM2 variants. There were 4 clinical phenotypes: (1) documented lethal arrhythmic events (LAEs): 4 carriers of N98S in CALM1 or CALM2; (2) suspected LAEs: CALM2 p.D96G and D132G carriers experienced syncope and transient cardiopulmonary arrest under emotional stimulation; (3) critical cardiac complication: CALM2 p.D96V and p.E141K carriers showed severe cardiac dysfunction with QTc prolongation; and (4) neurological and developmental disorders: 2 carriers of CALM2 p.E46K showed cardiac phenotypes of CPVT. Beta-blocker therapy was effective in all cases except cardiac dysfunction, especially in combination with flecainide (CPVT-like phenotype) and mexiletine (LQTS-like)., Conclusions: Calmodulinopathy patients presented severe cardiac features, and their onset of LAEs was earlier in life, requiring diagnosis and treatment at the earliest age possible.

Barth syndrome (BTHS) is an X-linked disorder characterized by cardiomyopathy, skeletal myopathy, and 3-methylglutaconic aciduria. The causative pathogenic variants for BTHS are in TAZ, which encodes a putative acyltransferase named tafazzin and is involved in the remodeling of cardiolipin in the inner mitochondrial membranes. Pathogenic variants in TAZ result in mitochondrial structural and functional abnormalities. We report a case of infantile BTHS with severe heart failure, left ventricular noncompaction, and lactic acidosis, having a missense c.640C>T (p.His214Tyr) variant in TAZ, which is considered a pathogenic variant based on the previously reported amino acid substitution at the same site (c.641A>G, p.His214Arg). However, in this previously reported case, heart function was compensated and not entirely similar to the present case. Silico prediction analysis suggested that c.640C>T could alter the TAZ messenger RNA (mRNA) splicing process. TAZ mRNAs in isolated peripheral mononuclear cells from the patient and in vitro splicing analysis using minigenes of TAZ found an 8 bp deletion at the 3' end of exon 8, which resulted in the formation of a termination codon in the coding region of exon 9 (H214Nfs*3). These findings suggest that splicing abnormalities should always be considered in BTHS., (© 2023 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC.)

Atrial tachyarrhythmias (ATAs), which may occur after tetralogy of Fallot (TOF) surgery, can cause sudden cardiac death. However, ATAs may also develop in response to electrical substrates. This study aims to examine the predictive factors for ATAs by identifying electrical substrates in the atrium obtained from 12-lead electrocardiogram in patients who underwent TOF repair. A total of 144 patients aged >15 years (median, 31.6 years) who underwent TOF repair at Hokkaido University were enrolled. We investigated the correlation between the development of ATAs with age, time interval after initial corrective surgery, brain natriuretic peptide levels, cardiac magnetic resonance parameters (right ventricular end-diastolic volume index, right ventricular end-systolic volume index, right ventricular ejection fraction, right atrial volume index, left ventricular end-diastolic volume index, left ventricular ejection fraction), and 12-lead electrocardiogram parameters (P wave maximum voltage, PR interval, QRS width, number of fragmented QRS). Of the 144 patients, 44 patients (30.6%) developed ATAs. Multivariate analysis revealed time interval after initial corrective surgery (odds ratio 6.7, 95% confidence interval 1.78 to 12.6) and PR interval (odds ratio 2.7, 95% confidence interval: 1.17 to 4.20) as independent risk factors for the development of ATAs. The receiver operating characteristic curve revealed a PR interval cut-off value of >200 milliseconds as predictive of the development of ATAs in patients more than 15 years after initial corrective surgery (area under the curve, 0.658; sensitivity, 71.4%; specificity, 66.4%). The present study demonstrated that a prolonged PR interval is a simple and convenient predictor for the development of ATAs in patients who underwent TOF repair., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objective: To evaluate the phosphorylation of estrogen receptor α at serine-118 (phospho-ERα S118) in the endometrium, ovarian endometrioma, and deep infiltrating endometriosis (DIE)., Design: Experimental study., Setting: University-affiliated hospital and academic research laboratory., Patient(s): Twenty-five patients underwent a hysterectomy, 18 patients underwent surgical removal of ovarian endometrioma, and 6 patients underwent DIE., Intervention(s): Tissue samples were obtained from patients who underwent surgical procedures., Main Outcome Measure(s): Immunostaining for phospho-ERα S118, ERα, or phosphorylated p44/42 mitogen-activated protein kinase (phospho-p44/42 MAPK) was performed to evaluate the endometrium with or without endometriosis, ovarian endometrioma, and DIE. For in vitro analysis, endometrial epithelial cells (Ishikawa cells) were stimulated with estradiol (E2) or tumor necrosis factor alpha (TNFα), and the expression levels of phospho-ERα S118 and phospho-p44/42 MAPK were evaluated via Western blotting., Result(s): First, phospho-ERα S118 level was significantly higher in the glands and stroma of ovarian endometriosis samples than in those of endometrial and DIE samples. Second, colocalization of phospho-p44/42 MAPK and phospho-ERα S118 was observed in the glands of ovarian endometrioma. The proportions of cells strongly expressing phospho-p44/42 and phospho-ERα were 87% in phosphor-p44/42 MAPK-positive cells and 79% in phosphor-ERα-positive cells. Third, E2 stimulation significantly enhanced phospho-ERα S118 after 15 and 30 minutes in in vitro analysis using endometrial epithelial cells. Fourth, TNFα stimulation modestly but significantly enhanced phospho-ERα S118 after 15 and 30 minutes. Fifth, in Ishikawa cells, treatment with a p44/42 inhibitor (PD98059) significantly reduced phospho-ERα S118 by TNFα but not by E2., Conclusion(s): ERα-S118 phosphorylation was increased in ovarian endometriosis. Our findings may provide a new perspective for understanding the mechanism of increased ERα action in the pathophysiology of endometriosis., (Copyright © 2022 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

The purpose of this study was to establish a novel mouse model of adenomyosis suitable for longitudinal and quantitative analyses and perinatal outcome studies. Using a 30 G needle, the entire uterine wall of one horn was mechanically punctured at a frequency of 100 times/1 cm (adenomyosis horn). The other horn was left unpunctured (control horn). Balb/c mice were sacrificed on day 14 (D14) or day 65 (D65) (n = 3 each). The uterus was fixed, paraffin-embedded, sliced, and stained. Lesions were detected and counted, and their volumes were measured. Cell proliferation and fibrosis were assessed by Ki67 and Masson's Trichrome staining, respectively. Blood vessels were detected using CD31 immunostaining. Some of the mice (n = 4), were mated and the date of delivery, litter size, number of implantations, and number and volume of postpartum lesions were measured. The number of lesions per horn did not differ between D14 and D65. The volume of the entire lesion was significantly greater on D65 than on D14 (p < 0.0001). The volume of the epithelial part of the lesion was significantly greater in D65 (p < 0.0001). The volume of the stromal part of the lesion was also greater on D65 (p < 0.0001). The percentage of Ki67 positive cells in the epithelial part of the lesion was significantly higher on D14 (p < 0.05). In contrast, the percentage of Ki67-positive cells in the stromal part was significantly higher on D65 (p < 0.01). Vascular density in the lesions was higher in on D65 (p < 0.05). The percentage of fibrotic area was significantly higher on D65 (p < 0.01). The date of delivery was slightly earlier than that reported for healthy mice of the same strain. The litter size was smaller than that reported in previous research. The number of implantation sites did not differ between the control and the adenomyosis horn. The number and volume of lesions did not differ between the non-pregnant and postpartum groups. This model can be applied to evaluate the pathogenesis of adenomyosis, validate the efficacy of therapeutic agents, and evaluate the effect of adenomyosis on pregnancy and vice versa., (© 2022. The Author(s).)

The purpose of this study was to establish a new mouse model of endometriosis that mimics real-world women's health problems, in which women continue to be affected by endometriosis long before they wish to become pregnant, and to evaluate the impact of "chronic exposure to endometriosis" on perinatal outcome. Endometriosis was established by the intraperitoneal injection of homologous minced mouse uteri. Vehicle was injected for the control. Mating was initiated either 1 or 43 days after disease establishment (Young or Aged studies, respectively). Mice were sacrificed on 18 dpc. The number pups and resorptions were counted and pups' body weights (BW) were measured, and the endometriosis lesion was identified and weighted. In the Young study, the number of resorptions and BW were comparable between the groups. In the Aged study, the number of resorptions was significantly higher and BW was significantly lower in endometriosis than that in control. The total weight of endometriosis lesion per dam was significantly lower in the Aged compared to the Young endometriosis group; however, not a single mouse was found to have any lesions at all. These results suggest that in addition to the presence of endometriosis per se, "chronic exposure to endometriosis" prior to pregnancy affect perinatal outcomes.

The risk factors and the appropriate interventions for perioperative junctional ectopic tachycardia (JET) in congenital heart disease (CHD) surgery have not been sufficiently investigated despite the severity of this complication. This study aimed to examine the risk factors and interventions for perioperative JET. From 2013 to 2020, 1062 surgeries for CHD (median patient age: 4.3 years, range 0.0-53.0) with or without a cardiopulmonary bypass (CPB) were performed at Hokkaido University, Japan. We investigated the correlation between perioperative JET morbidity factors, such as age, genetic background, CPB/aortic cross-clamp (ACC) time, use of inotropes and dexmedetomidine, STAT score, and laboratory indices. The efficacy of JET therapies was also evaluated. Of the 1062 patients, 86 (8.1%) developed JET. The 30-day mortality was significantly high in JET groups (7% vs. 0.8%). The independent risk factors for JET included heterotaxy syndrome [odds ratio (OR) 4.83; 95% confidence interval (CI) 2.18-10.07], ACC time exceeding 90 min (OR 1.90; CI 1.27-2.39), and the use of 3 or more inotropes (OR 4.11; CI 3.02-5.60). The combination of anti-arrhythmic drugs and a temporary pacemaker was the most effective therapy for intractable JET. Perioperative JET after CHD surgery remains a common cause of mortality. Inotrope use was a risk factor for developing JET overall surgery risk. In short ACC surgeries, heterotaxy syndrome could increase the risk of JET, which could develop even without inotrope use in long ACC surgeries. It is crucial not to delay the treatment in cases with unstable hemodynamics caused by this arrhythmia. It is recommended to reduce numbers not dose of inotropes., (© 2022. Springer Japan KK, part of Springer Nature.)

Biplane Area-Length (AL) method by left ventriculography (LVG) has been widely adopted as a standard method to estimate left ventricular volume. However, we have experienced difficulties in adopting the value by AL method for the children with Tetralogy of Fallot (TOF) due to the discrepancy among volumetric modalities. This study validated some limitations of AL method, considering the basic principles of its formulation. A single center retrospective cohort study was conducted for 1 year. The confirmed 22 cases with repaired TOF at our hospital were enrolled. The clinical characteristics, some cardiac MRI analyses, and all the cardiac catheterization studies were collected. Angiographic data were compared with historic cohorts of Kawasaki disease without any coronary artery lesions by using AL method. Cardiac MRI analyses of ten TOF patients were additionally available. LVG studies showed that the length of the long axis on anteroposterior view (AP) was not equal to that on lateral view (LT) due to anatomically apical elevation in TOF, followed by a significant difference found in the sagittal lengths of the LV long axis between AP and LT (P = 0.003). Because the difference critically affected the formula depending on biplane AL method, the calculated LVEDV of TOF group appeared overestimated, compared with the control group (TOF vs control group: 119.5% ± 6.3% vs 96.4 ± 3.5% of Normal, P = 0.006). Available cardiac MRI analyses of some patients in TOF group revealed 55% increase of LVEDV by AL method (angiocardiography 116 ± 7.0 vs CMR 75 ± 3.7 ml/m 2 , P = 0.0025). A pitfall exists when applying biplane AL method to measure LV volume especially for TOF patients, because the long axis on AP view is not always identical to that on LT view., (© 2022. Springer Japan KK, part of Springer Nature.)

Respiratory syncytial virus (RSV) is a common pathogen that causes extremely severe respiratory symptoms in the first few weeks and months of life. In infants with cardiopulmonary diseases, RSV infections have a significant clinical impact. Palivizumab, a humanised monoclonal antibody for RSV, has been shown to significantly reduce the rate of hospitalisation of high-risk infants diagnosed with RSV. However, we have experienced a significant number of RSV infections in our institution that required hospitalisation or intensive care, despite the administration of palivizumab. This study aimed to analyse the risk factors associated with severe RSV despite the use of palivizumab. We retrospectively reviewed the medical records of 688 patients who visited or were admitted to our hospital and received palivizumab. Thirty-seven (5.4%) patients required hospitalisation for RSV, despite receiving palivizumab. In addition, 31 of these patients (83.8%) required hospitalisation out of season for palivizumab injection. Preterm birth (≤ 28-week gestation), bronchopulmonary dysplasia (BPD), and trisomy 21 were risk factors for RSV-related hospitalisation in infected patients, despite receiving palivizumab. Furthermore, subgroup analysis of 69 patients with RSV revealed that hemodynamically significant congenital heart disease (CHD) was also a risk factor for RSV-related hospitalisation.Conclusion: Preterm birth (≤ 28 weeks of gestation), BPD, trisomy 21, hemodynamically significant CHD, and CHD requiring surgery or cardiac catheterisation/intervention during infancy could be considered when determining whether year-round administration of palivizumab is appropriate. What is Known: • Respiratory syncytial virus causes severe respiratory symptoms in infants, particularly those with cardiopulmonary diseases. • The use of palivizumab has reduced the rate of hospitalisation of infants diagnosed with RSV. Despite this, the rate of hospitalisation is still high. What is New: • We identified that preterm birth (≤ 28-week gestation), bronchopulmonary dysplasia, trisomy 21, and hemodynamically significant congenital heart disease were risk factors for RSV-related hospitalisation, even after receiving palivizumab treatment. • High-risk infants should be closely monitored and the prolonged use of palivizumab should be considered., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

A case of hypertrophic cardiomyopathy in the transition from childhood to adulthood, which was low risk by the conventional risk assessment model, medium risk by the adult risk prediction model, and high risk by the paediatric risk prediction model, was inserted an implantable cardioverter-defibrillator. Three years post-implantation, the patient was resuscitated with an appropriate discharge of cardioverter-defibrillator.

Objectives: This study aimed to determine the systemic and local proportions, focal localization, and characteristics of polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) in endometriosis., Study Design: Peripheral blood and peritoneal fluid were obtained from patients with a benign gynecologic condition (controls) or endometriosis. PMN-MDSCs were defined as CD33 + HLA-DR low/- CD14 - CD15 + and monocytic (M)-MDSCs were defined as CD33 + HLA-DR low/- CD14 + CD15 - , and were identified using flowcytometry. Ovarian endometriotic tissues were obtained, and the expression of lectin-type oxidized low density lipoprotein receptor-1 (LOX1) as a marker of PMN-MDSCs, arginine 1 (Arg1), and matrix metalloproteinase 9 (MMP9) were detected using immunohistochemistry. Anti-Ly6G antibody was administered to endometriosis model mice, and the number and weight of the lesions were measured, and cell proliferations and apoptosis in the lesions were analyzed using Ki67 immunohistochemistry and TUNEL assay., Results: In the peripheral blood, the proportion of PMN-MDSCs was significantly higher in endometriosis (3.20 vs 1.63 %, p < 0.05), but the proportion of M-MDSCs did not differ between the groups. In the peritoneal fluid, the proportion of PMN-MDSCs was significantly higher in endometriosis (7.82 × 10 -1 % vs 6.48 × 10 -2 %, p < 0.05), whereas the proportion of M-MDSCs did not differ between the groups. PMN-MDSCs were detected in the stromal cell layer of the endometriotic cyst wall. Double staining for LOX1 and Arg1, and LOX1 and MMP9 was confirmed. Administration of Ly6G antibody did not change the number or weight of endometriosis lesions, but significantly decreased Ki67-positive cells and increased TUNEL-positive cells in the lesions., Conclusions: PMN-MDSCs may contribute to the pathogenesis of endometriosis via Arg1 and MMP9 expression., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Dendritic cells (DC) in the lung that induce Th17 differentiation remain incompletely understood, in part because conventional CD11b + DCs (cDC2) are heterogeneous. Here, we report a population of cDCs that rapidly accumulates in lungs of mice following house dust extract inhalation. These cells are Ly-6C + , are developmentally and phenotypically similar to cDC2, and strongly promote Th17 differentiation ex vivo. Single cell RNA-sequencing (scRNA-Seq) of lung cDC2 indicates 5 distinct clusters. Pseudotime analysis of scRNA-Seq data and adoptive transfer experiments with purified cDC2 subpopulations suggest stepwise developmental progression of immature Ly-6C + Ly-6A/E + cDC2 to mature Ly-6C - CD301b + lung resident cDC2 lacking Ccr7 expression, which then further mature into CD200 + migratory cDC2 expressing Ccr7. Partially mature Ly-6C + Ly-6A/E - CD301b - cDC2, which express Il1b, promote Th17 differentiation. By contrast, CD200 + mature cDC2 strongly induce Th2, but not Th17, differentiation. Thus, Th17 and Th2 differentiation are promoted by lung cDC2 at distinct stages of maturation., (© 2021. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Background: We report a rare case of left ventricular inflow obstruction from a branch of the left circumflex coronary artery to the right atrium caused by a coronary arteriovenous fistula (CAVF) in a young Japanese male child., Case Presentation: The patient was diagnosed with CAVF following a heart murmur shortly after birth. The left-to-right shunt caused right ventricular volume overload and pulmonary congestion. An emergency surgical intervention was performed for the CAVF on day 6 after birth. However, by 5 years of age, his left ventricular inflow obstruction worsened. We found an abnormal blood vessel originating from the proximal part of a branch of the left circumflex coronary artery, circling the outside of the mitral valve annulus along the medial side of the coronary sinus. As the child gets older, the blood inflow into the left ventricle might get restricted further, resulting in left-sided heart failure., Conclusion: Our findings suggest that even after CAVF closure surgery, it is essential to monitor for complications caused by progressive dilatation of a persistent CAVF., (© 2021. The Author(s).)

We describe a 15-year-old girl who underwent intraoperative catheter ablation for the ventricular tachycardia associated with Ebstein's anomaly with functional pulmonary atresia and a small right ventricle (RV) after Fontan surgery. The computed tomography showed the dilated right atrium and RV due to the failure of RV plication. The activation mapping revealed that the ventricular tachycardia showed a focal pattern originating from the atrialized RV (aRV). With careful preparations, the procedure of catheter ablation combined with the adjustment of Starnes fenestration and plication of RV/atrialized RV was very effective for this patient., (© The Author(s) 2020. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

We described a 15-year-old boy who underwent the catheter ablation for the nodoventricular (NV) tachycardia that had difficulty in differentiation from atrioventricular nodal reentrant tachycardia with upper common pathway. The modification of the fast pathway revealed an anterograde conduction of the NV fiber. We successfully performed the catheter ablation targeting for the right ventricular insertion site of the NV fiber., (© 2020 Wiley Periodicals LLC.)

A 2-year-old male with right isomerism was referred for supraventricular tachycardias. Atrial pacing study revealed that anterograde conduction was only through the posterior atrioventricular node. During the mapping of ventriculoatrial conduction, we identified a sharp potential resembling a His-bundle electrogram with a decremental property at the anterior wall of the common atrium. Catheter ablation for the potential eliminated the anterior ventriculoatrial conduction, thereby indicating retrograde activation of the possible anterior atrioventricular node.

Childhood obstructive sleep apnoea syndrome (OSAS) secondary to adenoid hyperplasia is known to give rise to pulmonary hypertension. However, we present a case of a toddler with pulmonary hypertension (PH) and right heart failure due to OSAS, the cause of which is difficult to identify. After the patient underwent an adenotonsillectomy, OSAS disappeared and the PH eventually resolved. Both paediatricians and otolaryngologists should know that paediatric OSAS can occur even in the setting of mild, clinically insignificant palatine tonsil hypertrophy and adenoid hyperplasia. Surgical intervention should be considered without losing the opportunity if it could be the cause of PH., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Congenital heart disease-associated pulmonary arterial hypertension (CHD-PAH) is one of the major complications in patients with CHD. A timely closure of the left-to-right shunt will generally result in the normalization of the pulmonary hemodynamics, but a few patients have severe prognosis in their early childhood. We hypothesized that wide-ranging pathological mechanism in PAH could elucidate the clinical state of severe CHD-PAH. Using electronic medical records, we retrospectively analyzed six infants with severe CHD-PAH who had treatment-resistant PH. All patients were born with congenital malformation syndrome. After starting on a pulmonary vasodilator, five of the six patients developed complications including pulmonary edema and interstitial lung disease (ILD), and four patients had alveolar hemorrhage. After steroid therapy, the clinical condition improved in four patients, but two patients died. The autopsy findings in one of the deceased patients indicated the presence of recurrent alveolar hemorrhage, pulmonary venous hypertension, ILD, and PAH. Based on the clinical course of these CHD-PAH in patients and the literature, CHD-PAH can occur with pulmonary vascular obstructive disease (PVOD)/pulmonary capillary hemangiomatosis (PCH), ILD, and/or alveolar hemorrhage. The severity of CHD-PAH may depend on a genetic disorder, respiratory infection, and upper airway stenosis. Additionally, pulmonary vasodilators may be involved in the development of PVOD/PCH and ILD. When patients with CHD-PAH show unexpected deterioration, clinicians should consider complications associated with PVOD/PCH and/or pulmonary disease. In addition, the choice of upfront combination therapy for pediatric patients with CHD-PAH should be selected carefully.

Aims: Mitochondrial cardiomyopathy (MCM) is difficult to make a definite diagnosis because of various cardiovascular phenotypes and no diagnostic criteria in the pathology examination. We aim to add myocardial pathology to the diagnostic criteria for mitochondrial respiratory chain disorders., Methods: Quantitative analysis of mitochondria using electron microscopy and immunohistopathological analysis with respiratory chain enzyme antibodies were performed in 11 patients with hypertrophic or restrictive cardiomyopathy who underwent endomyocardial biopsy for possible MCM . Respiratory chain enzymatic assay in biopsied myocardium and genetic studies were also performed in all the subjects to define MCM., Results: Four patients were diagnosed with MCM according to the recent criteria of mitochondrial respiratory chain disorders. Using electron microscopy with quantitative analysis, the volume density of mitochondria within cardiac muscle cells was significantly increased in the MCM group compared with the non-MCM group (p=0.007). Immunohistopathological results were compatible with the result of the respiratory chain enzymatic assay., Conclusions: Pathological diagnosis of MCM could be confirmed by a quantitative study of electron microscopy and immunohistopathological analysis using the mitochondrial respiratory chain enzyme subunit antibody., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)