RESUMO
Worldwide prevalence of obesity is associated with the increase of lifestyle-related diseases. The accumulation of intermuscular adipose tissue (IMAT) is considered a major problem whereby obesity leads to sarcopenia and metabolic disorders and thus is a promising target for treating these pathological conditions. However, whereas obesity-associated IMAT is suggested to originate from PDGFRα+ mesenchymal progenitors, the processes underlying this adipogenesis remain largely unexplored. Here, we comprehensively investigated intra- and extracellular changes associated with these processes using single-cell RNA sequencing and mass spectrometry. Our single-cell RNA sequencing analysis identified a small PDGFRα+ cell population in obese mice directed strongly toward adipogenesis. Proteomic analysis showed that the appearance of this cell population is accompanied by an increase in galectin-3 in interstitial environments, which was found to activate adipogenic PPARγ signals in PDGFRα+ cells. Moreover, IMAT formation during muscle regeneration was significantly suppressed in galectin-3 knockout mice. Our findings, together with these multi-omics datasets, could unravel microenvironmental networks during muscle regeneration highlighting possible therapeutic targets against IMAT formation in obesity.
Assuntos
Tecido Adiposo/metabolismo , Galectina 3/metabolismo , Músculo Esquelético/fisiologia , Receptor alfa de Fator de Crescimento Derivado de Plaquetas/metabolismo , Actinas/genética , Actinas/metabolismo , Adipogenia , Tecido Adiposo/citologia , Animais , Cardiotoxinas/farmacologia , Diferenciação Celular , Senescência Celular/genética , Dieta Hiperlipídica , Feminino , Galectina 3/deficiência , Galectina 3/genética , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Músculo Esquelético/citologia , Músculo Esquelético/efeitos dos fármacos , Obesidade/metabolismo , Obesidade/patologia , PPAR gama/metabolismo , Receptor alfa de Fator de Crescimento Derivado de Plaquetas/deficiência , Receptor alfa de Fator de Crescimento Derivado de Plaquetas/genética , Regeneração , Transdução de Sinais/genéticaRESUMO
As a space project, in "Stem Cells" by the Japan Aerospace Exploration Agency (JAXA), frozen mouse ES cells were stored on the International Space Station (ISS) in the Minus Eighty Degree Laboratory Freezer for ISS (MELFI) for 1584 days. After taking these cells back to the ground, the cells were thawed and cultured, and their gene expressions were comprehensively analyzed using RNA sequencing in order to elucidate the early response of the cells to long-time exposure to space radiation consisting of various ionized particles. The comparisons of gene expression involved in double-stranded break (DSB) repair were examined. The expressions of most of the genes that were involved in homologous recombination (HR) and non-homologous end joining (NHEJ) were not significantly changed between the ISS-stocked cells and ground-stocked control cells. However, the transcription of Trp53inp1 (tumor protein 53 induced nuclear protein-1), Cdkn1a (p21), and Mdm2 genes increased in ISS-stocked cells as well as Fe ion-irradiated cells compared to control cells. This suggests that accumulated DNA damage caused by space radiation exposure would activate these genes, which are involved in cell cycle arrest for repair and apoptosis in a p53-dependent or -independent manner, in order to prevent cells with damaged genomes from proliferating and forming tumors.
Assuntos
Quebras de DNA de Cadeia Dupla , Células-Tronco Embrionárias Murinas , Animais , Camundongos , Reparo do DNA , Reparo do DNA por Junção de Extremidades , Análise de Sequência de RNA , Perfilação da Expressão GênicaRESUMO
Adenoviruses are used extensively as gene transfer agents, both experimentally and clinically. However, targeting of liver cells by adenoviruses compromises their potential efficacy. In cell culture, the adenovirus serotype 5 fiber protein engages the coxsackievirus and adenovirus receptor (CAR) to bind cells. Paradoxically, following intravascular delivery, CAR is not used for liver transduction, implicating alternate pathways. Recently, we demonstrated that coagulation factor (F)X directly binds adenovirus leading to liver infection. Here, we show that FX binds to the Ad5 hexon, not fiber, via an interaction between the FX Gla domain and hypervariable regions of the hexon surface. Binding occurs in multiple human adenovirus serotypes. Liver infection by the FX-Ad5 complex is mediated through a heparin-binding exosite in the FX serine protease domain. This study reveals an unanticipated function for hexon in mediating liver gene transfer in vivo.
Assuntos
Adenovírus Humanos/fisiologia , Proteínas do Capsídeo/metabolismo , Fator X/metabolismo , Fígado/virologia , Transdução Genética , Internalização do Vírus , Adenovírus Humanos/química , Adenovírus Humanos/classificação , Animais , Proteínas do Capsídeo/química , Proteínas de Transporte/metabolismo , Microscopia Crioeletrônica , Fator X/química , Hepatócitos/virologia , Humanos , Imageamento Tridimensional , Camundongos , Camundongos Transgênicos , Modelos Moleculares , Filogenia , Ligação Proteica/efeitos dos fármacos , Domínios e Motivos de Interação entre Proteínas , Ressonância de Plasmônio de Superfície , Varfarina/farmacologiaRESUMO
PURPOSE: A four-parameter risk model that included cardiac iodine-123 metaiodobenzylguanidine (MIBG) imaging and readily available clinical parameters was recently developed for prediction of 2-year cardiac mortality risk in patients with chronic heart failure. We sought to validate the ability of this risk model to predict post-discharge clinical outcomes in patients with acute decompensated heart failure (ADHF) and to compare its prognostic value with that of the Acute Decompensated Heart Failure National Registry (ADHERE) and Get With The Guidelines-Heart Failure (GWTG-HF) risk scores. METHODS: We studied 407 consecutive patients who were admitted for ADHF and survived to discharge, with definitive 2-year outcomes (death or survival). Cardiac MIBG imaging was performed just before discharge. The 2-year cardiac mortality risk was calculated using four parameters, namely age, left ventricular ejection fraction, New York Heart Association functional class, and cardiac MIBG heart-to-mediastinum ratio on delayed images. Patients were stratified into three groups based on the 2-year cardiac mortality risk: low- (< 4%), intermediate- (4-12%), and high-risk (> 12%) groups. The ADHERE and GWTG-HF risk scores were also calculated. RESULTS: There was a significant difference in the incidence of cardiac death among the three groups stratified using the 2-year cardiac mortality risk model (p < 0.0001). The 2-year cardiac mortality risk model had a higher C-statistic (0.732) for the prediction of cardiac mortality than the ADHERE and GWTG-HF risk scores. CONCLUSION: The 2-year MIBG-based cardiac mortality risk model is useful for predicting post-discharge clinical outcomes in patients with ADHF. TRIAL REGISTRATION NUMBER: UMIN000015246, 25 September 2014.
Assuntos
3-Iodobenzilguanidina , Insuficiência Cardíaca , Assistência ao Convalescente , Insuficiência Cardíaca/diagnóstico por imagem , Humanos , Radioisótopos do Iodo , Alta do Paciente , Prognóstico , Medição de Risco , Volume Sistólico , Função Ventricular EsquerdaRESUMO
Context dependency is a key feature in sequential structures of human language, which requires reference between words far apart in the produced sequence. Assessing how long the past context has an effect on the current status provides crucial information to understand the mechanism for complex sequential behaviors. Birdsongs serve as a representative model for studying the context dependency in sequential signals produced by non-human animals, while previous reports were upper-bounded by methodological limitations. Here, we newly estimated the context dependency in birdsongs in a more scalable way using a modern neural-network-based language model whose accessible context length is sufficiently long. The detected context dependency was beyond the order of traditional Markovian models of birdsong, but was consistent with previous experimental investigations. We also studied the relation between the assumed/auto-detected vocabulary size of birdsong (i.e., fine- vs. coarse-grained syllable classifications) and the context dependency. It turned out that the larger vocabulary (or the more fine-grained classification) is assumed, the shorter context dependency is detected.
Assuntos
Tentilhões/fisiologia , Redes Neurais de Computação , Vocalização Animal/classificação , Algoritmos , Animais , Análise por Conglomerados , Biologia Computacional , Masculino , Memória/fisiologia , Vocalização Animal/fisiologiaRESUMO
Deep learning using an end-to-end convolutional neural network (ConvNet) has been applied to several electroencephalography (EEG)-based brain-computer interface tasks to extract feature maps and classify the target output. However, the EEG analysis remains challenging since it requires consideration of various architectural design components that influence the representational ability of extracted features. This study proposes an EEG-based emotion classification model called the multi-kernel temporal and spatial convolution network (MultiT-S ConvNet). The multi-scale kernel is used in the model to learn various time resolutions, and separable convolutions are applied to find related spatial patterns. In addition, we enhanced both the temporal and spatial filters with a lightweight gating mechanism. To validate the performance and classification accuracy of MultiT-S ConvNet, we conduct subject-dependent and subject-independent experiments on EEG-based emotion datasets: DEAP and SEED. Compared with existing methods, MultiT-S ConvNet outperforms with higher accuracy results and a few trainable parameters. Moreover, the proposed multi-scale module in temporal filtering enables extracting a wide range of EEG representations, covering short- to long-wavelength components. This module could be further implemented in any model of EEG-based convolution networks, and its ability potentially improves the model's learning capacity.
Assuntos
Interfaces Cérebro-Computador , Eletroencefalografia , Humanos , Eletroencefalografia/métodos , Redes Neurais de Computação , Emoções , Cuidados PaliativosRESUMO
To initiate adaptive immunity, dendritic cells (DCs) move from parenchymal tissues to lymphoid organs by migrating along stromal scaffolds that display the glycoprotein podoplanin (PDPN). PDPN is expressed by lymphatic endothelial and fibroblastic reticular cells and promotes blood-lymph separation during development by activating the C-type lectin receptor, CLEC-2, on platelets. Here, we describe a role for CLEC-2 in the morphodynamic behavior and motility of DCs. CLEC-2 deficiency in DCs impaired their entry into lymphatics and trafficking to and within lymph nodes, thereby reducing T cell priming. CLEC-2 engagement of PDPN was necessary for DCs to spread and migrate along stromal surfaces and sufficient to induce membrane protrusions. CLEC-2 activation triggered cell spreading via downregulation of RhoA activity and myosin light-chain phosphorylation and triggered F-actin-rich protrusions via Vav signaling and Rac1 activation. Thus, activation of CLEC-2 by PDPN rearranges the actin cytoskeleton in DCs to promote efficient motility along stromal surfaces.
Assuntos
Movimento Celular/fisiologia , Células Dendríticas/metabolismo , Lectinas Tipo C/metabolismo , Glicoproteínas de Membrana/metabolismo , Actinas/metabolismo , Imunidade Adaptativa/fisiologia , Animais , Células Apresentadoras de Antígenos/metabolismo , Plaquetas/metabolismo , Células Cultivadas , Células Dendríticas/imunologia , Embrião de Mamíferos , Células Endoteliais/metabolismo , Endotélio Linfático/citologia , Endotélio Linfático/metabolismo , Feminino , Citometria de Fluxo , Proteínas de Fluorescência Verde/metabolismo , Humanos , Lectinas Tipo C/genética , Lectinas Tipo C/imunologia , Linfonodos/citologia , Linfonodos/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Microscopia Confocal , Cadeias Leves de Miosina/metabolismo , Ativação Plaquetária , Gravidez , Proteínas Proto-Oncogênicas c-vav/metabolismo , Transdução de Sinais/fisiologia , Pele/citologia , Pele/metabolismo , Técnicas de Cultura de Tecidos , Proteínas rac1 de Ligação ao GTP/metabolismo , Proteína rhoA de Ligação ao GTP/metabolismoRESUMO
BACKGROUND: The impact of chronic kidney disease (CKD) on long-term outcomes following acute myocardial infarction (AMI) in the era of modern primary PCI with optimal medical therapy is still in debate.MethodsâandâResults:A total of 3,281 patients with AMI were enrolled in the J-MINUET registry, with primary PCI of 93.1% in STEMI. CKD stage on admission was classified into: no CKD (eGFR ≥60 mL/min/1.73 m2); moderate CKD (60>eGFR≥30 mL/min/1.73 m2); and severe CKD (eGFR <30 mL/min/1.73 m2). While the primary endpoint was all-cause mortality, the secondary endpoint was major adverse cardiac events (MACE), defined as a composite of all-cause death, cardiac failure, myocardial infarction (MI) and stroke. Of the 3,281 patients, 1,878 had no CKD, 1,073 had moderate CKD and 330 had severe CKD. Pre-person-days age- and sex-adjusted in-hospital mortality significantly increased from 0.014% in no CKD through 0.042% in moderate CKD to 0.084% in severe CKD (P<0.0001). Three-year mortality and MACE significantly deteriorated from 5.09% and 15.8% in no CKD through 16.3% and 38.2% in moderate CKD to 36.7% and 57.9% in severe CKD, respectively (P<0.0001). C-index significantly increased from the basic model of 0.815 (0.788-0.841) to 0.831 (0.806-0.857), as well as 0.731 (0.708-0.755) to 0.740 (0.717-0.764) when adding CKD stage to the basic model in predicting 3-year mortality (P=0.013; net reclassification improvement [NRI] 0.486, P<0.0001) and MACE (P=0.046; NRI 0.331, P<0.0001) respectively. CONCLUSIONS: CKD remains a useful predictor of in-hospital and 3-year mortality as well as MACE after AMI in the modern PCI and optimal medical therapy era.
Assuntos
Infarto do Miocárdio , Intervenção Coronária Percutânea , Insuficiência Renal Crônica , Hospitais , Humanos , Intervenção Coronária Percutânea/efeitos adversos , Fatores de Risco , Resultado do TratamentoRESUMO
Thrombolysis in Myocardial Infarction Risk Score for Secondary Prevention (TRS2°P) is a contemporary risk scoring system for secondary prevention based on nine clinical factors. However, this scoring system has not been validated in other populations. The aim of this study was to validate the TRS2°P in patients with acute myocardial infarction (AMI) treated with primary percutaneous coronary intervention (PCI) in a nationwide registry cohort. Among 3283 consecutive patients with AMI enrolled in the Japanese registry of acute Myocardial INfarction diagnosed by Universal dEfiniTion (J-MINUET), a total of 2611 patients who underwent primary PCI were included in this study. The performance of the TRS2°P to predict major adverse cardiovascular events (MACE) composed of all-cause death, non-fatal MI, and non-fatal stroke up to 3 years in the present cohort was evaluated. The TRS2°P had modest discriminative performance in this J-MINUET cohort with a c-statistic of 0.63, similar to that in the derived cohort (TRA2°P-TIMI50, c-statistic 0.67). A strong graded relationship between the TRS2°P and 3-year cardiovascular event rates was also observed in the J-MINUET cohort. Age ≥ 75 years, Killip ≥ 2, prior stroke, peripheral artery disease, anemia, and non-ST-elevation myocardial infarction were identified as independent factors for the incidence of MACE. The TRS2°P modestly predicted secondary cardiovascular events among patients with AMI treated by primary PCI in a nationwide cohort of Japan. Further studies are needed to develop a novel risk score better predicting secondary cardiovascular events.
Assuntos
Infarto do Miocárdio , Intervenção Coronária Percutânea , Idoso , Humanos , Infarto do Miocárdio/epidemiologia , Medição de Risco , Fatores de Risco , Prevenção Secundária , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/prevenção & controleRESUMO
Long-term clinical outcomes among patients with cardiogenic shock (CS) and heart failure (HF) who survive the early phase of acute myocardial infarction (AMI) remain uncertain. We investigated 3283 consecutive patients with AMI, selected from a prospective, nation-wide multicenter registry (J-MINUET) database comprising 28 institutions in Japan between July 2012 and March 2014. The 3263 eligible patients were divided into the following three groups: CS-/HF- group (n = 2467, 75.6%); CS-/HF+ group (n = 479, 14.7%); and CS+ group (n = 317, 9.7%). The thirty-day mortality rate in CS+ patients was 32.8%, significantly higher than in CS- patients. Among CS+ patients, multivariate logistic regression analysis identified statin use before admission (Odds ratio (OR) 0.32, 95% confidence interval (CI) 0.14-0.66, P = 0.002), renal deficiency (OR 8.72, 95%CI 2.81-38.67, P < 0.0001) and final thrombolysis in myocardial infarction flow grade (OR 0.42, 95%CI 0.18-0.99, P = 0.046) were associated with 30-day mortality. Landmark Kaplan-Meier analysis showed that mortality rates after 30 days were comparable between CS+ and CS-/HF+ groups but were lower in the CS-/HF- group. Multivariate Cox hazard analysis also showed that hazard risk of mortality after 30 days was comparable between the CS+ and CS-/HF+ groups (Hazard ratio (HR) 1.03, 95%CI 0.63-1.68, P = 0.90), and significantly lower in the CS-/HF- group (HR 0.44, 95%CI 0.32-059, P < 0.0001). In conclusion, AMI patients with CS who survived 30 days experienced worse long-term outcomes compared with those without CS up to 3 years. Attention is required for patients who show HF on admission without CS to improve long-term AMI outcomes.
Assuntos
Insuficiência Cardíaca/complicações , Choque Cardiogênico/complicações , Idoso , Feminino , Humanos , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Choque Cardiogênico/mortalidadeRESUMO
BACKGROUND: AdreView myocardial imaging for risk evaluation in heart failure (ADMIRE-HF) risk score is a novel risk score to predict serious arrhythmic risk in chronic heart failure patients with reduced ejection fraction (HFrEF). Moreover, early repolarization pattern (ERP) has been shown to be associated with an increased risk of sudden cardiac death (SCD) in HFrEF patients. We sought to investigate the prognostic value of combining ADMIRE-HF risk score and ERP to predict SCD in HFrEF patients. METHODS: We studied 90 HFrEF outpatients with LVEF< 40% in our prospective cohort study. In cardiac MIBG imaging, the heart-to-mediastinum (H/M) ratio was measured on the delayed planar image. ADMIRE-HF risk score was derived from the sum of the point values of LVEF, H/M ratio, and systolic blood pressure. We also assessed ERP on the standard electrocardiogram. RESULTS: During a median follow-up of 7.5(4.5-12.0) years, 22 patients had SCD. At multivariate Cox analysis, ADMIRE-HF risk score and ERP were independently associated with SCD. Patients with both intermediate/high ADMIRE-HF score and ERP had a higher SCD risk than those with either and none of them. CONCLUSION: The combination of ADMIRE-HF risk score and ERP would provide the incremental prognostic information for predicting SCD in HFrEF patients.
Assuntos
Morte Súbita Cardíaca , Insuficiência Cardíaca/diagnóstico por imagem , Insuficiência Cardíaca/mortalidade , 3-Iodobenzilguanidina , Idoso , Doença Crônica , Eletrocardiografia/métodos , Feminino , Seguimentos , Coração/fisiopatologia , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Miocárdio/patologia , Prevalência , Prognóstico , Modelos de Riscos Proporcionais , Estudos Prospectivos , Compostos Radiofarmacêuticos , Risco , Medição de Risco , Volume Sistólico , Tomografia Computadorizada de Emissão de Fóton Único/métodos , Disfunção Ventricular Esquerda/complicaçõesRESUMO
BACKGROUND: Second-generation drug-eluting stents (DES) reduce the incidence of stent thrombosis, even in patients with ST-segment elevated myocardial infarction (STEMI). However, the early local vascular healing after DES implantation in STEMI lesions, which mainly concerns stent thrombosis, is still unclear.MethodsâandâResults:We attempted to determine early local vascular healing 3 months after cobalt-chromium everolimus-eluting stent (CoCr-EES) implantation in STEMI lesions relative to stable coronary artery disease (CAD) lesions. This prospective, multicenter study analyzed 96 total lesions (STEMI=49, stable CAD=51) by frequency domain-optical coherence tomography (FD-OCT) performed post-procedure and at the 3-month follow-up. Although CoCr-EES implanted in STEMI were almost entirely covered at 3 months, they had a relatively high incidence of uncovered struts compared with stable CAD (5.5% vs. 1.6%, P<0.001). Intrastent thrombus in the 2 groups was primarily resolved at the 3-month follow-up (STEMI: 91.7%â26.5%, stable CAD: 74.5%â11.8%). Regarding irregular protrusion, complete resolution was observed in stable CAD (21.6%â0%), while a few stents remained in STEMI (79.2%â8.2%). Although there were almost no changes for the serial change of average lumen area in STEMI, there were slight but significant decreases in stable CAD [STEMI 0.08 (-0.44, 0.55) mm2, stable CAD -0.35 (-0.55, 0.11) mm2; P=0.009]. CONCLUSIONS: Although strut coverage after CoCr-EES implantation for STEMI lesions was slightly delayed, the healing process appeared to be acceptable in both STEMI and stable CAD.
Assuntos
Doença da Artéria Coronariana , Stents Farmacológicos , Everolimo/administração & dosagem , Infarto do Miocárdio com Supradesnível do Segmento ST , Trombose , Cromo , Cobalto , Humanos , Intervenção Coronária Percutânea , Estudos Prospectivos , Infarto do Miocárdio com Supradesnível do Segmento ST/cirurgia , Trombose/prevenção & controle , Tomografia de Coerência Óptica , Resultado do TratamentoRESUMO
BACKGROUND: Chronic spontaneous urticaria (CSU) is defined as the spontaneously appearing weals and/or angioedema for more than 6 weeks. Dietary habits can modulate the pathogenesis of CSU. However, dietary intakes of nutrients or food in CSU patients, compared with healthy controls, have not been examined in quality and quantity. METHODS: We evaluated dietary habits in adult Japanese patients with chronic spontaneous urticaria using a validated, brief-type self-administered diet history questionnaire and compared the results to those of age- and sex-matched healthy controls. The severity of CSU was evaluated using the Urticaria Control Test. RESULTS: Japanese CSU patients showed higher body mass indices, higher intakes of eggs, vegetables other than green/yellow vegetables/mushrooms/algae, cholesterol, folic acid, dietary fibres, vitamin D, vitamin K, Cu, Fe, Pi, Ca, Mg, Na and salt, and lower intake of alcohol, compared to controls. The logistic regression analysis showed that CSU was associated with high body mass index and high intake of eggs. The intake of beverages was higher in uncontrolled CSU patients (Urticaria Control Test â¦11 points) than in controlled patients. The logistic regression analysis showed that uncontrolled CSU was associated with high intake of beverages. The intake of coffee, caffeine-rich and non-alcohol beverage, in uncontrolled CSU patients was higher than that in controlled patients. CONCLUSIONS: Chronic spontaneous urticaria was associated with high body mass index and high intake of eggs. Uncontrolled CSU was associated with high intake of beverages. Further studies should elucidate the relationships of these results with the development or exacerbation of CSU.
Assuntos
Bebidas , Índice de Massa Corporal , Urticária Crônica/epidemiologia , Dieta , Ovos , Adulto , Idoso , Estudos de Casos e Controles , Comportamento Alimentar , Feminino , Humanos , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Autorrelato , Índice de Gravidade de Doença , VerdurasRESUMO
Discordant results have been reported on outcomes of acute myocardial infarction (AMI) patients who present during off-hours.We investigated 3283 consecutive patients with AMI who were selected from the prospective, nationwide, multicenter registry (J-MINUET) database comprising 28 institutions in Japan between July 2012 and March 2014 to determine the current impact of off-hours presentation (defined as weekends, holidays, and weekdays from 8:01 PM to 7:59 AM) at hospitals on long-term clinical outcomes. The primary endpoint was a composite of all-cause death, non-fatal MI, non-fatal stroke, cardiac failure, and urgent revascularization for unstable angina for up to 3 years from the index event.During off-hours, 52% of patients presented. Primary percutaneous coronary intervention was performed in 85% of patients, and the door-to-balloon time was comparable between off-hours and regular hours (74, interquartile range [IQR] 52 to 113 versus 75, IQR 52 to 126 minutes, P = 0.34). Rate of overall primary endpoint overall did not overall significantly differ (25.3% versus 23.5%, log-rank P = 0.26), in patients with ST-elevation myocardial infarction (STEMI) (log-rank P = 0.93) and in patients with non-ST-elevation myocardial infarction (NSTEMI) (log-rank P = 0.14). Multivariate Cox regression analysis showed that off-hours presentation was not significantly associated with long-term clinical events in all cohorts.The impact of presentation during off-hours or regular hours on the long-term clinical outcomes of Japanese patients with AMI is comparable in contemporary practice.
Assuntos
Infarto do Miocárdio , Admissão do Paciente/estatística & dados numéricos , Sistema de Registros , Idoso , Humanos , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de TempoRESUMO
Although B-type natriuretic peptide (BNP) has gradually gained recognition as an indicator in risk stratification for patients with acute myocardial infarction (AMI), the prognostic impact on long-term clinical outcomes in patients with non-ST-segment elevation acute myocardial infarction (NSTEMI) without creatine kinase (CK) elevation remains unclear.This prospective multicenter study assessed 3,283 consecutive patients with AMI admitted to 28 institutions in Japan between 2012 and 2014. We analyzed 218 patients with NSTEMI without CK elevation (NSTEMI-CK) for whom BNP was available. In the NSTEMI-CK group, patients were assigned to high- and low-BNP groups according to BNP values (cut-off BNP, 100 pg/mL). The primary endpoint was defined as a composite of all-cause death, non-fatal myocardial infarction, non-fatal stroke, cardiac failure, and urgent revascularization for unstable angina up to 3 years. Primary endpoints were observed in 60 (33.3%) events among patients with NSTEMI-CK. Kaplan-Meier analysis revealed a significantly higher event rate for primary endpoints among patients with high BNP (log-rank P < 0.001). After adjusting for covariates, a higher BNP level was significantly associated with long-term clinical outcomes in NSTEMI-CK (adjusted hazard ratio, 4.86; 95% confidence interval, 2.18-12.44; P < 0.001).The BNP concentration is associated with adverse long-term clinical outcomes among patients with NSTEMI-CK who are considered low risk. Careful clinical management may be warranted for secondary prevention in patients with NSTEMI-CK with high BNP levels.
Assuntos
Angina Instável/epidemiologia , Creatina Quinase/sangue , Insuficiência Cardíaca/epidemiologia , Mortalidade , Infarto do Miocárdio/epidemiologia , Peptídeo Natriurético Encefálico/sangue , Infarto do Miocárdio sem Supradesnível do Segmento ST/sangue , Acidente Vascular Cerebral/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Angina Instável/cirurgia , Causas de Morte , Feminino , Humanos , Japão/epidemiologia , Masculino , Revascularização Miocárdica/estatística & dados numéricos , Infarto do Miocárdio sem Supradesnível do Segmento ST/terapia , Prognóstico , Modelos de Riscos ProporcionaisRESUMO
BACKGROUND: The sympathetic nervous system provides an important trigger for major arrhythmic events through regional heterogeneity of sympathetic activity, which could be evaluated by SPECT imaging as the regional MIBG washout rate (WR). There is little information available on the prognostic value of regional WR in SPECT imaging for the prediction of sudden cardiac death (SCD) in patients with chronic heart failure (CHF). METHODS: We studied 73 CHF outpatients with LVEF < 40%. At study entry, the regional WR was measured in 17 segments on the polar map. We defined abnormal regional WR as both the regional WR range (maximum - minimum regional WR) and maximum regional WR > mean value + 2SD obtained in 15 normal controls. RESULTS: During a mean follow-up of 7.5 ± 4.1 years, 15 of 73 patients had SCD. The abnormal regional WR and abnormal global WR on planar images were significantly and independently associated with SCD. Patients with both the abnormal regional WR and global WR had a significantly higher risk of SCD than those with none of these criteria. CONCLUSIONS: The analysis of regional MIBG WR on SPECT imaging provides additional prognostic value to global WR on planar images for SCD prediction in CHF patients.
Assuntos
Morte Súbita Cardíaca , Insuficiência Cardíaca/diagnóstico por imagem , Tomografia Computadorizada de Emissão de Fóton Único , 3-Iodobenzilguanidina/química , Idoso , Doença Crônica , Ecocardiografia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Norepinefrina/sangue , Prognóstico , Estudos Prospectivos , Sistema Nervoso Simpático/diagnóstico por imagem , Disfunção Ventricular Esquerda/fisiopatologiaRESUMO
BACKGROUND: Beta-blockers are standard therapy for acute myocardial infarction (AMI). However, despite current advances in the management of AMI, it remains unclear whether all AMI patients benefit from ß-blockers. We investigated whether admission heart rate (HR) is a determinant of the effectiveness of ß-blockers for AMI patients. MethodsâandâResults: We enrolled 3,283 consecutive AMI patients who were admitted to 28 participating institutions in the Japanese Registry of Acute Myocardial Infarction Diagnosed by Universal Definition (J-MINUET) study. According to admission HR, we divided patients into 3 groups: bradycardia (HR <60 beats/min, n=444), normocardia (HR 60 to ≤100 beats/min, n=2,013), and tachycardia (HR >100 beats/min, n=342). The primary endpoint was major adverse cardiac events (MACE), including all-cause death, non-fatal MI, non-fatal stroke, heart failure (HF), and urgent revascularization for unstable angina, at 3-year follow-up. Beta-blocker at discharge was significantly associated with a lower risk of MACE in the tachycardia group (23.6% vs. 33.0%; P=0.033), but it did not affect rates of MACE in the normocardia group (17.8% vs. 18.4%; P=0.681). In the bradycardia group, ß-blocker use at discharge was significantly associated with a higher risk of MACE (21.6% vs. 12.7%; P=0.026). Results were consistent for multivariable regression and stepwise multivariable regression. CONCLUSIONS: Admission HR might determine the efficacy of ß-blockers for current AMI patients.
Assuntos
Antagonistas Adrenérgicos beta/administração & dosagem , Frequência Cardíaca , Infarto do Miocárdio/tratamento farmacológico , Infarto do Miocárdio/mortalidade , Admissão do Paciente , Idoso , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Previous studies have demonstrated that use of intravascular ultrasound (IVUS) during percutaneous coronary intervention (PCI) was associated with lower incidence of death, myocardial infarction, and target vessel revascularization. Recently, optical coherence tomography (OCT) has emerged as an alternative intravascular imaging device with better resolution. The aim of this study was to investigate frequency and prognostic impact of IVUS or OCT-guided PCI during urgent revascularization for acute myocardial infarction diagnosed by the universal definition. A total of 2788 patients who underwent urgent PCI were selected from a multicenter, Japanese registry of acute myocardial infarction diagnosed by universal definition (J-MINUET). Frequency, clinical characteristics and prognostic impact of the IVUS-, or OCT- guided PCI were investigated. Clinical endpoint was in-hospital death. Angiography-, IVUS-, and OCT-guided urgent PCI were performed in 689 (24.7%), 1947 (69.8%), and 152 (5.5%) patients. In-hospital death in each group was 10.4%, 5.1%, and 3.3%, respectively (P < 0.01). By univariate and multivariate logistic regression analysis, IVUS-guided PCI (vs. angiography-guided PCI, OR 0.49, 95% CI 0.30-0.81, P = 0.006) was a significant independent predictor of in-hospital death. Intravascular imaging guided-PCI was frequently adopted during urgent PCI for acute myocardial infarction diagnosed by universal definition and was associated with better in-hospital survival.
Assuntos
Stents Farmacológicos , Infarto do Miocárdio/diagnóstico , Intervenção Coronária Percutânea/métodos , Sistema de Registros , Cirurgia Assistida por Computador/estatística & dados numéricos , Tomografia de Coerência Óptica/métodos , Ultrassonografia de Intervenção/métodos , Idoso , Angiografia Coronária , Feminino , Humanos , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/mortalidade , Infarto do Miocárdio/cirurgia , Taxa de Sobrevida/tendências , Resultado do TratamentoRESUMO
It is known that incidence and short-term mortality rate of acute myocardial infarction (AMI) tend to be higher in the cold season. The aim of our study was to investigate the association of onset-season with patient characteristics and long-term prognosis of AMI. This was a prospective, multicenter, Japanese investigation of 3,283 patients with AMI who were hospitalized within 48 h of symptom onset between July 2012 and March 2014. Patients were divided into 3 seasonal groups according to admission date: cold season group (December-March), hot season group (June-September), and moderate season group (April, May, October, and November). We identified 1356 patients (41.3%) admitted during the cold season, 901 (27.4%) during the hot season, and 1026 (31.3%) during the moderate season. We investigated the seasonal effect on patient characteristics and clinical outcomes. Baseline characteristics of each seasonal group were comparable, with the exception of age, Killip class, and conduction disturbances. The rates of higher Killip class and complete atrioventricular block were significantly higher in the cold season group. The 3-year cumulative survival free from major adverse cardiac events (MACE) rate was the lowest in the cold season (67.1%), showing a significant difference, followed by the moderate (70.0%) and hot seasons (72.9%) (p < 0.01). Initial severity and long-term prognoses were worse in patients admitted during the cold season. Our findings highlight the importance of optimal prevention and follow-up of AMI patients with cold season onset.
Assuntos
Infarto do Miocárdio/epidemiologia , Sistema de Registros , Medição de Risco/métodos , Estações do Ano , Idoso , Feminino , Seguimentos , Mortalidade Hospitalar/tendências , Humanos , Incidência , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/diagnóstico , Prognóstico , Estudos Prospectivos , Fatores de Risco , Fatores de TempoRESUMO
BACKGROUND: Although hyponatremia predicts morbidity and mortality in acute decompensated heart failure (ADHF), hypochloremia is also independently associated with poor prognosis in ADHF. Little is known, however, about the prognostic value of serial change in serum chloride during hospitalization in ADHF patients.MethodsâandâResults:We prospectively studied 208 ADHF survivors after discharge and divided them into 4 groups according to serum chloride on admission and at discharge: (1) persistent hypochloremia group (n=12), hypochloremia both on admission and at discharge; (2) progressive hypochloremia group (n=42), development of hypochloremia after admission; (3) improved hypochloremia group (n=14), hypochloremia only on admission; and (4) no hypochloremia group, no hypochloremia during hospitalization (n=140). During a mean follow-up period of 1.86±0.76 years, 20 of 208 patients had heart failure death (HFD). In a model adjusted for hyponatremia, hypochloremia both on admission and at discharge was still significantly associated with HFD. Hyponatremia, however, was not significantly associated with HFD after adjustment for hypochloremia. Patients with persistent hypochloremia (HR, 9.13; 95% CI: 2.56-32.55) and with progressive hypochloremia (HR, 4.65; 95% CI: 1.61-13.4) had a significantly greater risk of HFD than those without hypochloremia during hospitalization. CONCLUSIONS: Both persistent hypochloremia and progressive hypochloremia during hospitalization are associated with HFD in ADHF patients.