RESUMO

BACKGROUND Polymer-free drug-coated stents provide superior clinical outcomes to bare-metal stents in patients at high bleeding risk who undergo percutaneous coronary intervention (PCI) and are treated with 1 month of dual antiplatelet therapy. Data on the use of polymer-based drug-eluting stents, as compared with polymer-free drug-coated stents, in such patients are limited. METHODS In an international, randomized, single-blind trial, we compared polymer-based zotarolimus-eluting stents with polymer-free umirolimus­coated stents in patients at high bleeding risk. After PCI, patients were treated with 1 month of dual antiplatelet therapy, followed by single antiplatelet therapy. The primary outcome was a safety composite of death from cardiac causes, myocardial infarction, or stent thrombosis at 1 year. The principal secondary outcome was target-lesion failure, an effectiveness composite of death from cardiac causes, target-vessel myocardial infarction, or clinically indicated target-lesion revascularization. Both outcomes were powered for noninferiority. RESULTS A total of 1996 patients at high bleeding risk were randomly assigned in a 1:1 ratio to receive zotarolimus-eluting stents (1003 patients) or polymer-free drugcoated stents (993 patients). At 1 year, the primary outcome was observed in 169 of 988 patients (17.1%) in the zotarolimus-eluting stent group and in 164 of 969 (16.9%) in the polymer-free drug-coated stent group (risk difference, 0.2 percentage points; upper boundary of the one-sided 97.5% confidence interval [CI], 3.5; noninferiority margin, 4.1; P=0.01 for noninferiority). The principal secondary outcome was observed in 174 patients (17.6%) in the zotarolimus-eluting stent group and in 169 (17.4%) in the polymer-free drug-coated stent group (risk difference, 0.2 percentage points; upper boundary of the one-sided 97.5% CI, 3.5; noninferiority margin, 4.4; P=0.007 for noninferiority). CONCLUSIONS Among patients at high bleeding risk who received 1 month of dual antiplatelet therapy after PCI, use of polymer-based zotarolimus-eluting stents was noninferior to use of polymer-free drug-coated stents with regard to safety and effectiveness composite outcomes. (Funded by Medtronic; ONYX ONE ClinicalTrials.gov number, NCT03344653.). (AU)

Assuntos

Doença da Artéria Coronariana/tratamento farmacológico , Terapia Combinada , Sirolimo , Stents Farmacológicos , Polímeros , Método Duplo-Cego

RESUMO

The originally-proposed PRECISE-DAPT score is a 5-item risk score supporting decision-making for dual antiplatelet therapy1 duration after PCI. It is unknown if a simplified version of the score based on 4 factors (age, hemoglobin, creatinine clearance, prior bleeding), and lacking white-blood cell count, retains potential to guide DAPT duration. The 4-item PRECISE-DAPT was used to categorize 10,081 patients who were randomized to short (3-6 months) or long (12-24 months) DAPT regimen according to high (HBR defined by PRECISE-DAPT ≥25 points) or non-high bleeding risk (PRECISE-DAPT<25) status. Long treatment duration was associated with higher bleeding rates in HBR (ARD +2.22% [95% CI +0.53 to +3.90]) but not in non-HBR patients (ARD +0.25% [-0.14 to +0.64]; pint = 0.026), and associated with lower ischemic risks in non-HBR (ARD -1.44% [95% CI -2.56 to -0.31]), but not in HBR patients (ARD +1.16% [-1.91 to +4.22]; pint = 0.11). Only non-HBR patients experienced lower net clinical adverse events (NACE) with longer DAPT (pint = 0.043). A 4-item simplified version of the PRECISE-DAPT score retains the potential to categorize patients who benefit from prolonged DAPT without concomitant bleeding liability from those who do not. (AU)

Assuntos

Inibidores da Agregação Plaquetária/uso terapêutico , Tomada de Decisão Clínica

RESUMO

PURPOSE: Abdominal lymph node (ALN) recurrence in gastric cancer (GC) is rare and usually unresectable. We investigated the effects of integration of radiotherapy (RT) and chemotherapy against ALN recurrence in GC. METHODS: We retrospectively categorized GC patients with ALN recurrence treated between 2005 and 2013 into two groups: those treated with integration of RT and chemotherapy (RCT) and those who received systemic chemotherapy only (CT). The median follow-up period after ALN recurrence for all patients was 20 months. RESULTS: Of 53 patients, 31 and 22 were in the RCT and CT groups, respectively. Isolated distant failure (DF; 35.5%) without local progression (LP) was the dominant pattern of failure (POF) in the RCT group (median DF-free period, 26 months). LP followed by DF (31.8%) was the dominant POF in the CT group; LP (median LP-free period, 8 months) occurred 10 months earlier than DF (median DF-free period, 18 months). RCT patients had significantly longer median progression-free survival (PFS) compared to CT patients (25 vs. 8 months; P = 0.021). On multivariate analysis, treatment (CT vs. RCT) was an independent prognostic factor for PFS (hazard ratio 2.085; 95% confidence interval 1.073-4.050; P = 0.013). CONCLUSIONS: Integration of RT and chemotherapy achieved long-term local control and prolonged PFS in GC patients with ALN recurrence. Local RT is feasible for treating isolated ALN recurrences.

Assuntos

Adenocarcinoma/terapia , Carcinoma de Células em Anel de Sinete/terapia , Quimiorradioterapia , Linfonodos/patologia , Recidiva Local de Neoplasia/prevenção & controle , Neoplasias Gástricas/terapia , Adenocarcinoma/secundário , Adulto , Idoso , Carcinoma de Células em Anel de Sinete/secundário , Feminino , Seguimentos , Humanos , Linfonodos/efeitos dos fármacos , Linfonodos/efeitos da radiação , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Recidiva Local de Neoplasia/patologia , Prognóstico , Estudos Retrospectivos , Neoplasias Gástricas/patologia , Taxa de Sobrevida

RESUMO

Stimulation by a number of conditions, including infection, cytokines, mechanical injury, and hypoxia, can upregulate inducible nitric oxide synthase (iNOS) in hepatocytes. We observed that exposure to hypergravity significantly upregulated the transcription of the hepatic iNOS gene. The aim of this study was to confirm our preliminary data, and to further investigate the distribution of the iNOS protein in the livers of mice exposed to hypergravity. ICR mice were exposed to +3 Gz for 1 h. We investigated the time course of change in the iNOS expression. Hepatic iNOS mRNA expression progressively increased in centrifuged mice from 0 to 12 h, and then decreased rapidly by 18 h. iNOS mRNA levels in the livers of centrifuged mice was significantly higher at 3, 6, and 12 h than in uncentrifuged control mice. The pattern of iNOS protein expression paralleled that of the mRNA expression. At 0 and 1 h, weak cytoplasmic iNOS immunoreactivity was found in some hepatocytes surrounding terminal hepatic venules. It was noted that at 6 h there was an increase in the number of perivenular hepatocytes with moderate to strong cytoplasmic immunoreactivity. The number of iNOS-positive hepatocytes was maximally increased at 12 h. The majority of positively stained cells showed a strong intensity of iNOS expression. The expression levels of iNOS mRNA and protein were significantly increased in the livers of mice exposed to hypergravity. These results suggest that exposure to hypergravity significantly upregulates iNOS at both transcriptional and translational levels.

Assuntos

Animais , Expressão Gênica/fisiologia , Hipergravidade , Fígado/enzimologia , Óxido Nítrico Sintase Tipo II/metabolismo , RNA Mensageiro/metabolismo , Ensaio de Imunoadsorção Enzimática , Hipergravidade/efeitos adversos , Imuno-Histoquímica , Mediadores da Inflamação/metabolismo , Interferon gama/análise , Interleucina-1beta/análise , /análise , Fígado/anatomia & histologia , Fígado/fisiologia , Camundongos Endogâmicos ICR , Óxido Nítrico Sintase Tipo II/genética , Biossíntese de Proteínas/fisiologia , Reação em Cadeia da Polimerase em Tempo Real , Transcrição Gênica/fisiologia , Fator de Necrose Tumoral alfa/análise , Regulação para Cima/fisiologia

RESUMO

Korean rose bitterling (Rhodeus uyekii) is a freshwater fish endemic to Korea. Natural populations of this species have experienced severe declines as a result of habitat fragmentation and water pollution. To conserve and restore R. uyekii, the genetic diversity of this species needs to be assessed at the population level. Eighteen novel polymorphic microsatellite loci for R. uyekii were developed using an enriched partial genomic library. Polymorphisms at these loci were studied in 150 individuals collected from three populations. The number of alleles at each locus ranged from 3 to 47 (mean = 17.1). Within the populations, the observed heterozygosity ranged from 0.032 to 1.000, expected heterozygosity from 0.082 to 0.967, and polymorphism information content from 0.078 to 0.950. Six loci showed significant deviation from Hardy-Weinberg equilibrium after Bonferroni's correction, and no significant linkage disequilibrium was detected between most locus pairs, except in three cases. These highly informative microsatellite markers should be useful for genetic population structure analyses of R. uyekii.

Assuntos

Peixes/genética , Biblioteca Genômica , Repetições de Microssatélites , Alelos , Animais , Genótipo , Polimorfismo Genético

RESUMO

Stimulation by a number of conditions, including infection, cytokines, mechanical injury, and hypoxia, can upregulate inducible nitric oxide synthase (iNOS) in hepatocytes. We observed that exposure to hypergravity significantly upregulated the transcription of the hepatic iNOS gene. The aim of this study was to confirm our preliminary data, and to further investigate the distribution of the iNOS protein in the livers of mice exposed to hypergravity. ICR mice were exposed to +3 Gz for 1 h. We investigated the time course of change in the iNOS expression. Hepatic iNOS mRNA expression progressively increased in centrifuged mice from 0 to 12 h, and then decreased rapidly by 18 h. iNOS mRNA levels in the livers of centrifuged mice was significantly higher at 3, 6, and 12 h than in uncentrifuged control mice. The pattern of iNOS protein expression paralleled that of the mRNA expression. At 0 and 1 h, weak cytoplasmic iNOS immunoreactivity was found in some hepatocytes surrounding terminal hepatic venules. It was noted that at 6 h there was an increase in the number of perivenular hepatocytes with moderate to strong cytoplasmic immunoreactivity. The number of iNOS-positive hepatocytes was maximally increased at 12 h. The majority of positively stained cells showed a strong intensity of iNOS expression. The expression levels of iNOS mRNA and protein were significantly increased in the livers of mice exposed to hypergravity. These results suggest that exposure to hypergravity significantly upregulates iNOS at both transcriptional and translational levels.

Assuntos

Expressão Gênica/fisiologia , Hipergravidade , Fígado/enzimologia , Óxido Nítrico Sintase Tipo II/metabolismo , RNA Mensageiro/metabolismo , Animais , Ensaio de Imunoadsorção Enzimática , Hipergravidade/efeitos adversos , Imuno-Histoquímica , Mediadores da Inflamação/metabolismo , Interferon gama/análise , Interleucina-1beta/análise , Interleucina-6/análise , Fígado/anatomia & histologia , Fígado/fisiologia , Camundongos Endogâmicos ICR , Óxido Nítrico Sintase Tipo II/genética , Biossíntese de Proteínas/fisiologia , Reação em Cadeia da Polimerase em Tempo Real , Transcrição Gênica/fisiologia , Fator de Necrose Tumoral alfa/análise , Regulação para Cima/fisiologia

Assuntos

Galopamil/farmacologia , Infarto do Miocárdio/tratamento farmacológico , Miocárdio/patologia , Verapamil/análogos & derivados , Animais , Contração Miocárdica/efeitos dos fármacos , Infarto do Miocárdio/mortalidade , Infarto do Miocárdio/patologia , Prognóstico , Ratos , Ratos Endogâmicos

RESUMO

A finalidade deste estudo foi avaliar os efeitos de metoxi-verapamil (D-600) na mortalidade e no tamanho final do infarto, em ratos com oclusao coronariana. Inicialmente, o tronco comum da coronaria esquerda foi ocluido em 212 ratos. Os animais foram randomizados em um grupo controle e um grupo tratado com D-600. A mortalidade apos os primeiros 15 minutos da oclusao do tronco comum da arteria coronaria esquerda era 40% menor no grupo tratado que no grupo controle (p < 0,01). A diferenca de mortalidade entre os dois grupos manteve-se 48 horas apos a oclusao. Os ratos que sobreviveram 48 horas apos-oclusao coronaria tiveram seus infartos medidos por planimetria e os resultados foram: 38,2% no grupo controle e 37,6% no grupo tratado. Estes resultados permitem-nos concluir que D-600 diminui a mortalidade apos oclusao coronariana em ratos, provavelmente por acao antiarritmica

Assuntos

Galopamil , Miocárdio , Infarto do Miocárdio