Background:Low population density may be associated with high mortality in acute myocardial infarction (AMI) patients. The purpose of this study was to investigate the effect of population density ...and hospital primary percutaneous coronary intervention (PCI) volume on AMI in-hospital mortality in Japan.Methods and Results:This is a retrospective study of 64,414 AMI patients transported to hospital by ambulances. The main outcome measure was in-hospital mortality. The median population density was 1,147 (interquartile range, 342–5,210) persons/km2. There was a significant negative relationship between population density and in-hospital mortality (OR for a quartile down in population density 1.086, 95% CI 1.042–1.132, P<0.001). Patients in less densely populated areas were more often transported to hospitals with a lower primary PCI volume, and they had a longer distance to travel. By using multivariable analysis, primary PCI volume was found to be significantly associated with in-hospital mortality, but distance to hospital was not. When divided into the low- and high-volume hospitals, using the cut-off value of 115 annual primary PCI procedures, the increase in in-hospital mortality associated with low population density was observed only in patients hospitalized in the low-volume hospitals.Conclusions:Increased in-hospital mortality related to low population density was observed only in AMI patients who were transported to the low primary PCI volume hospitals, but not in those who were transported to high-volume hospitals.
Background:Congenital heart disease (CHD) is often diagnosed prenatally using fetal echocardiography, but few studies have evaluated the accuracy of these fetal cardiac diagnoses in detail. We ...investigated the discrepancy between pre- and postnatal diagnoses of CHD and the impact of discrepant diagnoses.Methods and Results:This retrospective study at a tertiary institution included data from the medical records of 207 neonates with prenatally diagnosed CHD admitted to the cardiac neonatal intensive care unit between January 2011 and December 2016. Pre- and postnatal diagnoses of CHD differed in 12% of neonates. Coarctation of the aorta and ventricular septal defects were the most frequent causes of discrepant diagnosis. Unexpected treatments were added to 38% of discrepant diagnostic cases. However, discrepant diagnoses did not adversely affect the clinical course. The 9% of the 207 neonates who required invasive intervention within 24 h of delivery were accurately diagnosed prenatally.Conclusions:Pre- and postnatal diagnoses differed in only a few neonates, with differences not adversely affecting the clinical course. Neonates who required invasive intervention immediately after delivery were accurately diagnosed prenatally. Prenatal diagnosis thus seems to contribute to improved prognosis in neonates with CHD.
Defective mitochondrial dynamics through aberrant interactions between mitochondria and actin cytoskeleton is increasingly recognized as a key determinant of cardiac fragility after myocardial ...infarction (MI). Dynamin-related protein 1 (Drp1), a mitochondrial fission-accelerating factor, is activated locally at the fission site through interactions with actin. Here, we report that the actin-binding protein filamin A acted as a guanine nucleotide exchange factor for Drp1 and mediated mitochondrial fission-associated myocardial senescence in mice after MI. In peri-infarct regions characterized by mitochondrial hyperfission and associated with myocardial senescence, filamin A colocalized with Drp1 around mitochondria. Hypoxic stress induced the interaction of filamin A with the GTPase domain of Drp1 and increased Drp1 activity in an actin-binding-dependent manner in rat cardiomyocytes. Expression of the A1545T filamin mutant, which potentiates actin aggregation, promoted mitochondrial hyperfission under normoxia. Furthermore, pharmacological perturbation of the Drp1-filamin A interaction by cilnidipine suppressed mitochondrial hyperfission-associated myocardial senescence and heart failure after MI. Together, these data demonstrate that Drp1 association with filamin and the actin cytoskeleton contributes to cardiac fragility after MI and suggests a potential repurposing of cilnidipine, as well as provides a starting point for innovative Drp1 inhibitor development.
Aims
Data on the long‐term outcomes of individuals with hepatitis B virus (HBV) infection who are hepatitis envelope antigen (HBeAg)‐negative inactive carriers (ICs) are limited due to small numbers. ...We compared the long‐term prognosis of well‐defined ICs with that of age‐ and gender‐matched general population controls.
Methods
A total of 526 HBeAg‐negative patients who demonstrated alanine aminotransferase (ALT) level ≤40 U/L and HBV DNA level ≤4.3 log IU/ml at least three times within 1 year after the start of follow‐up were enrolled as ICs. Inactive carriers were divided into two groups: Group A (n = 332), whose ALT level was ≤30 U/L and HBV DNA level was ≤3.3 log IU/ml, and Group B (remaining patients, n = 194). We determined the long‐term prognosis of ICs and compared it with that of general population controls. We also analyzed factors associated with hepatitis B surface antigen (HBsAg) clearance and phase transition in ICs.
Results
There were no significant differences in hepatocellular carcinoma development or all‐cause, liver‐related, or non–liver‐related mortality between Groups A and B. There was no significant difference in all‐cause mortality between ICs and the general population. Low HBsAg level (≤3.0 log IU/ml) and the presence of fatty liver were associated with HBsAg clearance and high alpha‐fetoprotein level was associated with phase transition.
Conclusions
The long‐term prognosis of well‐defined ICs was similar to that of general population controls. In addition, the ICs had a high HBsAg clearance rate and low phase transition rate.
Weather conditions affect the incidence of acute myocardial infarction (AMI). However, little is known on the association of weather temperature and humidity with AMI hospitalizations in a ...super-aging society. This study sought to examine this association. We included 87,911 consecutive patients with AMI admitted to Japanese acute-care hospitals between April 1, 2012 and March 31, 2015. The primary outcome was the number of AMI hospitalizations per day. Multilevel mixed-effects linear regression models were used to estimate the association of the average temperature and humidity, 1 day before hospital admission, with AMI hospitalizations, after adjusting for weather, hospital, and patient demographics.Lower temperature and humidity were associated with an increased number of AMI hospitalizations (coefficient - 0.500 - 0.524 to - 0.474 per °C change, p < 0.001 and coefficient - 0.012 - 0.023 to - 0.001 per % change, p = 0.039, respectively). The effects of temperature and humidity on AMI hospitalization did not differ by age and sex (all interaction p > 0.05), but differed by season. However, higher temperatures in spring (coefficient 0.089 0.025 to 0.152 per °C change, p = 0.010) and higher humidity in autumn (coefficient 0.144 0.121 to 0.166 per % change, p < 0.001) were risk factors for AMI hospitalization. Increased average temperatures and humidity, 1 day before hospitalization, are associated with a decreased number of AMI hospitalizations.
Human induced pluripotent stem cells (hiPSCs) represent promising raw materials of human cell-based therapeutic products (hCTPs). As undifferentiated hiPSCs exhibit intrinsic tumorigenicity ...properties that enable them to form teratomas, hCTPs containing residual undifferentiated hiPSCs may cause tumor formation following transplantation. We first established quantitative and sensitive tumorigenicity testing of hiPSCs dissociated into single cells using NOD/Shi-scid IL2Rγnull (NOG) mice by inhibiting apoptosis of hiPSCs with a Rho kinase inhibitor. To examine different features in tumorigenicity of various hiPSCs, 10 commonly available hiPSC lines were subjected to in vivo tumorigenicity testing. Transplanted hiPSC lines showed remarkable variation in tumor incidence, formation latency, and volumes. Most of the tumors formed were classified as immature teratomas. However, no signs of malignancies, such as carcinoma and sarcoma, were recognized in the tumors. Characteristics associated tumorigenicity of hiPSCs were investigated with microarray analysis, karyotype analysis, and whole exome sequencing. Gene expression profiling and pathway analysis supported different features of hiPSC lines in tumorigenicity. hiPSC lines showed chromosomal abnormalities in some lines and 61-77 variants of cancer-related genes carrying effective nonsynonymous mutations, which were confirmed in the COSMIC databases. In this study, the chromosomal abnormalities and cancer-related gene mutations observed in hiPSC lines did not lead to the malignancy of tumors derived from hiPSCs. Our results suggest that the potential tumorigenicity risk of hCTPs containing residual undifferentiated hiPSCs is dependent on not only amounts of undifferentiated hiPSCs but also features of the cell lines used as raw materials, a finding that should be considered from the perspective of quality of hCTPs used.
Malnutrition is becoming one of the most important determinants of worse clinical outcomes in patients with acute heart failure (AHF). However, appropriate tools for evaluating the nutritional status ...in patients aged ≥65 years with AHF remain unclear. We examined 490 consecutive patients aged ≥65 years with AHF. They were divided into 2 groups according to Geriatric Nutritional Risk Index (GNRI; cut-off value = 92). During a median period of 189 days, the mortality rate was significantly higher in the lower GNRI group than the higher GNRI group (p <0.001). In multivariate analyses, lower GNRI was an independent determinant of adverse events (HR 0.92, 95% CI 0.88 to 0.95, p <0.001). The GNRI showed the best prognostic value (C-statistic: 0.70) among other nutritional indexes. Adding GNRI to an existing outcome prediction model for mortality in AHF significantly increased the C-statistic from 0.68 to 0.74 (p = 0.017). The net reclassification improvement afforded by GNRI was 60% overall, 27% for events, and 33% for nonevents (p <0.001). In conclusion, lower GNRI on admission was independently associated with worse clinical outcomes in patients aged ≥65 years with AHF, and it was superior to other nutritional parameters. Furthermore, the assessment of nutritional status using GNRI is very helpful for risk stratification.
Non‐hypervascular hypointense nodules (NHHNs) on gadolinium‐ethoxybenzyl‐diethylenetriamine pentaacetic acid–enhanced magnetic resonance imaging (EOB‐MRI) have a high likelihood of ...hypervascularization progressing to typical hypervascular hepatocellular carcinoma (HCC). NHHNs that were present before the start of anti‐hepatitis C virus (HCV) therapy is a risk marker for HCC development after achieving sustained virologic response (SVR). In this report, we show a patient without a previous history of HCC in whom HCC developed by hypervascularization of NHHN after SVR. This patient achieved SVR more than 8 years before NHHN developed into HCC, and during this time NHHN had been present but had remained unchanged in size and imaging features as shown by repeated EOB‐MRI. Hepatocarcinogenic potential of NHHNs persist for a long time after SVR, despite the eradication of HCV.
Background:Previous studies have reported that acute myocardial infarction (AMI) related to left anterior descending (LAD) lesion is associated with worse outcomes than left circumflex artery (LCX) ...or right coronary artery (RCA) lesions. However, it is unknown whether those relationships are still present in the contemporary era of primary percutaneous coronary intervention (PCI), using newer generation drug-eluting stents and potent antiplatelet agents.Methods and Results:This study is a sub-analysis of the Japan AMI Registry (JAMIR), a multicenter, prospective registry enrolling 3,411 AMI patients between December 2015 and May 2017. Among them, 2,780 patients undergoing primary PCI for only a culprit vessel were included and stratified based on infarction-related artery type (LAD, LCX, and RCA). The primary outcome was 1-year cardiovascular death. The overall incidence of cardiovascular death was 3.4%. Patients with LAD infarction had highest incidence of cardiovascular death compared to patients with LCX and RCA infarction (4.8%, 1.3%, and 2.4%, respectively); however, landmark analysis showed that culprit vessel had no significant effect on cardiovascular death if a patient survived 30 days after primary PCI. LAD lesion infarction was an independent risk factor for cardiovascular death in adjusted Cox regression analysis.Conclusions:The present sub-analysis of the JAMIR demonstrated that LAD infarction is still associated with worse outcomes, especially during the first 30 days, even in the contemporary era of PCI.
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