Double Congenital Fistulae with Aneurysm Diagnosed by Combining Imaging Modalities

Congenital coronary pulmonary artery fistula (CAF) is rare, and systemic-to-pulmonary artery fistula (SPAF) is even more so. Furthermore, congenital coronary pulmonary fistula associated with congenital SPAF is extremely rare. As far as we know, CAF and SPAF connected with an aneurysm have not been described very often. We described an 83-year-old woman with an aneurysm originating from a CAF connected to an aortopulmonary artery fistula. Chest radiography revealed a shadow at the left edge of the heart line. Multi-detector-row computed tomography (MDCT) with contrast enhancement and coronary cine angiography revealed that the shadow was an aneurysm connected to a tortuous fistula at the left anterior descending coronary artery. The aneurysm was formed by congenital coronary pulmonary and aortopulmonary artery fistulae. Echocardiography revealed predominantly systolic blood flow in the fistula from the left anterior descending coronary artery (LAD). Although neither MDCT, echocardiography nor coronary angiography alone could provide a comprehensive image of the anomaly, including the hemodynamics in the fistulae and their relationship with surrounding organs and tissues, their combination could provided important facts the led to a deeper understanding of this very uncommon occurrence

Prognostic Impact of Baseline Hemoglobin Levels on Long-Term Thrombotic and Bleeding Events After Percutaneous Coronary Interventions

Background: Association of baseline hemoglobin levels with long-term adverse events after percutaneous coronary interventions has not been yet thoroughly defined. We aimed to assess the clinical impact of baseline hemoglobin on long-term ischemic and bleeding risk after percutaneous coronary intervention. Methods and Results: Using the pooled individual patient-level data from the 3 percutaneous coronary intervention studies, we categorized 19 288 patients into 4 groups: high-normal hemoglobin (≥14.0 g/dL; n=7555), low-normal hemoglobin (13.0-13.9 g/dL in men and 12.0-13.9 g/dL in women; n=5303), mild anemia (11.0-12.9 g/dL in men and 11.0-11.9 g/dL in women; n=4117), and moderate/severe anemia (<11.0 g/dL; n=2313). Median follow-up duration was 3 years. Low-normal hemoglobin, mild anemia, and moderate/severe anemia correlated with significant excess risk relative to high-normal hemoglobin for GUSTO (Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Arteries Trial) moderate/severe bleeding, with adjusted hazard ratios of 1.22 (95% CI, 1.04-1.44), 1.73 (95% CI, 1.47-2.04), and 2.31 (95% CI, 1.92-2.78), respectively. Moderate/severe anemia also correlated with significant excess risk relative to high-normal hemoglobin for the ischemic composite end point of myocardial infarction/ischemic stroke (adjusted hazard ratio, 1.33; 95% CI, 1.11-1.60), whereas low-normal hemoglobin and mild anemia did not. However, the excess risk of low-normal hemoglobin, mild anemia, and moderate/severe anemia relative to high-normal hemoglobin remained significant for ischemic stroke and for mortality. Conclusions: Decreasing baseline hemoglobin correlated with incrementally higher long-term risk for major bleeding, ischemic stroke, and mortality after percutaneous coronary intervention. Even within normal range, lower baseline hemoglobin level correlated with higher ischemic and bleeding risk

A let-7 microRNA-RALB axis links the immune properties of iPSC-derived megakaryocytes with platelet producibility

iPS細胞由来血小板造血における免疫巨核球の制御機構の発見 血小板の大量製造に向けた巨核球マスターセルの品質管理に応用可能. 京都大学プレスリリース. 2024-03-26.Discovering a new microRNA-regulated pathway to boost iPS cell-derived platelet production. 京都大学プレスリリース. 2024-03-26.We recently achieved the first-in-human transfusion of induced pluripotent stem cell-derived platelets (iPSC-PLTs) as an alternative to standard transfusions, which are dependent on donors and therefore variable in supply. However, heterogeneity characterized by thrombopoiesis-biased or immune-biased megakaryocytes (MKs) continues to pose a bottleneck against the standardization of iPSC-PLT manufacturing. To address this problem, here we employ microRNA (miRNA) switch biotechnology to distinguish subpopulations of imMKCLs, the MK cell lines producing iPSC-PLTs. Upon miRNA switch-based screening, we find imMKCLs with lower let-7 activity exhibit an immune-skewed transcriptional signature. Notably, the low activity of let-7a-5p results in the upregulation of RAS like proto-oncogene B (RALB) expression, which is crucial for the lineage determination of immune-biased imMKCL subpopulations and leads to the activation of interferon-dependent signaling. The dysregulation of immune properties/subpopulations, along with the secretion of inflammatory cytokines, contributes to a decline in the quality of the whole imMKCL population

Lower doses of carvedilol in Japanese heart failure patients with reduced ejection fraction could show the potential to be non-inferior to higher doses in US patients: An international collaborative observational study

Maeda M., Humber D., Hida E., et al. (2024) Lower doses of carvedilol in Japanese heart failure patients with reduced ejection fraction could show the potential to be non-inferior to higher doses in US patients: An international collaborative observational study. PLoS ONE 19(3.0): e0299510. doi.org/10.1371/journal.pone.0299510.The Japanese national guidelines recommend significantly lower doses of carvedilol for heart failure with reduced ejection fraction (HFrEF) management than the US guidelines. Using real-world data, we determined whether initial and target doses of carvedilol in Japanese patients (JPNs) differ from those in US patients (USPs), especially in Asian Americans (ASA) and Caucasians (CA), and investigated differences in outcomes. We collected data from the electronic medical records, including demographics, carvedilol dosing, tolerability, cardiac functional indicators like EF, cardiovascular events including all-cause deaths, and laboratory values from the University of California, San Diego Health and Osaka University. JPNs had significantly lower doses (mg/day) of carvedilol initiation (66 USPs composed of 38 CAs and 28 ASAs, 17.1±16.2; 93 JPNs, 4.3±4.2, p<0.001) and one year after initiation (33.0±21.8; 11.2±6.5, p<0.001), and a significantly lower relative rate (RR) of dose discontinuation and reduction than USPs (RR: 0.406, 95% confidence interval (CI): 0.181–0.911, p<0.05). CAs showed the highest reduction rate (0.184), and ASAs had the highest discontinuation rate (0.107). A slight mean difference with narrow 95% CI ranges straddling zero was observed between the two regions in the change from the baseline of each cardiac functional indicator (LVEF, -0.68 [−5.49–4.12]; LVDd, −0.55 [−3.24–2.15]; LVDd index, −0.25 [−1.92–1.43]; LVDs, −0.03 [−3.84–3.90]; LVDs index, −0.04 [−2.38–2.30]; heart rate, 1.62 [−3.07–6.32]). The event-free survival showed no difference (p = 0.172) among the races. Conclusively, despite JPNs exhibiting markedly lower carvedilol doses, their dose effectiveness has the potential to be non-inferior to that in USPs. Dose de-escalation, not discontinuation, could be an option in some Asian and ASA HFrEF patients intolerable to high doses of carvedilol

The Role of Robo3 in the Development of Cortical Interneurons

A number of studies in recent years have shown that members of the Roundabout (Robo) receptor family, Robo1 and Robo2, play significant roles in the formation of axonal tracks in the developing forebrain and in the migration and morphological differentiation of cortical interneurons. Here, we investigated the expression and function of Robo3 in the developing cortex. We found that this receptor is strongly expressed in the preplate layer and cortical hem of the early cortex where it colocalizes with markers of Cajal–Retzius cells and interneurons. Analysis of Robo3 mutant mice at early (embryonic day [E] 13.5) and late (E18.5) stages of corticogenesis revealed no significant change in the number of interneurons, but a change in their morphology at E13.5. However, preliminary analysis on a small number of mice that lacked all 3 Robo receptors indicated a marked reduction in the number of cortical interneurons, but only a limited effect on their morphology. These observations and the results of other recent studies suggest a complex interplay between the 3 Robo receptors in regulating the number, migration and morphological differentiation of cortical interneurons

A Genome-Wide Association Study Identified AFF1 as a Susceptibility Locus for Systemic Lupus Eyrthematosus in Japanese

Systemic lupus erythematosus (SLE) is an autoimmune disease that causes multiple organ damage. Although recent genome-wide association studies (GWAS) have contributed to discovery of SLE susceptibility genes, few studies has been performed in Asian populations. Here, we report a GWAS for SLE examining 891 SLE cases and 3,384 controls and multi-stage replication studies examining 1,387 SLE cases and 28,564 controls in Japanese subjects. Considering that expression quantitative trait loci (eQTLs) have been implicated in genetic risks for autoimmune diseases, we integrated an eQTL study into the results of the GWAS. We observed enrichments of cis-eQTL positive loci among the known SLE susceptibility loci (30.8%) compared to the genome-wide SNPs (6.9%). In addition, we identified a novel association of a variant in the AF4/FMR2 family, member 1 (AFF1) gene at 4q21 with SLE susceptibility (rs340630; P = 8.3×10−9, odds ratio = 1.21). The risk A allele of rs340630 demonstrated a cis-eQTL effect on the AFF1 transcript with enhanced expression levels (P<0.05). As AFF1 transcripts were prominently expressed in CD4+ and CD19+ peripheral blood lymphocytes, up-regulation of AFF1 may cause the abnormality in these lymphocytes, leading to disease onset