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1.
Nat Commun ; 11(1): 4510, 2020 09 09.
Artigo em Inglês | MEDLINE | ID: mdl-32908143

RESUMO

With human median lifespan extending into the 80s in many developed countries, the societal burden of age-related muscle loss (sarcopenia) is increasing. mTORC1 promotes skeletal muscle hypertrophy, but also drives organismal aging. Here, we address the question of whether mTORC1 activation or suppression is beneficial for skeletal muscle aging. We demonstrate that chronic mTORC1 inhibition with rapamycin is overwhelmingly, but not entirely, positive for aging mouse skeletal muscle, while genetic, muscle fiber-specific activation of mTORC1 is sufficient to induce molecular signatures of sarcopenia. Through integration of comprehensive physiological and extensive gene expression profiling in young and old mice, and following genetic activation or pharmacological inhibition of mTORC1, we establish the phenotypically-backed, mTORC1-focused, multi-muscle gene expression atlas, SarcoAtlas (https://sarcoatlas.scicore.unibas.ch/), as a user-friendly gene discovery tool. We uncover inter-muscle divergence in the primary drivers of sarcopenia and identify the neuromuscular junction as a focal point of mTORC1-driven muscle aging.


Assuntos
Envelhecimento/fisiologia , Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo , Fibras Musculares Esqueléticas/patologia , Junção Neuromuscular/patologia , Sarcopenia/patologia , Envelhecimento/efeitos dos fármacos , Animais , Linhagem Celular , Modelos Animais de Doenças , Eletromiografia , Regulação da Expressão Gênica/efeitos dos fármacos , Regulação da Expressão Gênica/fisiologia , Humanos , Microdissecção e Captura a Laser , Masculino , Alvo Mecanístico do Complexo 1 de Rapamicina/antagonistas & inibidores , Alvo Mecanístico do Complexo 1 de Rapamicina/genética , Camundongos , Mioblastos , Junção Neuromuscular/efeitos dos fármacos , Técnicas de Patch-Clamp , RNA-Seq , Sarcopenia/genética , Sarcopenia/fisiopatologia , Sarcopenia/prevenção & controle , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética , Sirolimo/administração & dosagem
2.
Transplantation ; 104(8): 1686-1694, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32732848

RESUMO

BACKGROUND: It is commonly believed that mTOR inhibitors (mTORi) should not be used in high-immunological risk kidney transplant recipients due to a perceived increased risk of rejection. However, almost all trials that examined the association of optimal-dose mTORi with calcineurin inhibitor (CNI) have excluded hypersensitized recipients from enrollment. METHODS: To shed light on this issue, we examined 71 consecutive patients with a baseline calculated panel reactive antibody (cPRA) ≥50% that underwent kidney transplantation from June 2013 to December 2016 in our unit. Immunosuppression was based on CNI (tacrolimus), steroids and alternatively mycophenolic acid (MPA; n = 38), or mTORi (either everolimus or sirolimus, n = 33, target trough levels 3-8 ng/mL). RESULTS: Demographic and immunological risk profiles were similar, and almost 90% of patients in both groups received induction with lymphocyte-depleting agents. Cox-regression analysis of rejection-free survival revealed better results for mTORi versus MPA in terms of biopsy-proven acute rejection (hazard ratio [confidence interval], 0.32 [0.11-0.90], P = 0.031 at univariable analysis and 0.34 [0.11-0.95], P = 0.040 at multivariable analysis). There were no differences in 1-year renal function, Banff chronicity score at 3- and 12-month protocol biopsy and development of de novo donor-specific antibodies. Tacrolimus trough levels along the first year were not different between groups (12-mo levels were 8.72 ± 2.93 and 7.85 ± 3.07 ng/mL for MPA and mTORi group respectively, P = 0.277). CONCLUSIONS: This single-center retrospective cohort analysis suggests that in hypersensitized kidney transplant recipients receiving tacrolimus-based immunosuppressive therapy similar clinical outcomes may be obtained using mTOR inhibitors compared to mycophenolate.


Assuntos
Dessensibilização Imunológica/métodos , Rejeição de Enxerto/prevenção & controle , Imunossupressores/administração & dosagem , Transplante de Rim/efeitos adversos , Serina-Treonina Quinases TOR/antagonistas & inibidores , Adulto , Idoso , Inibidores de Calcineurina/administração & dosagem , Inibidores de Calcineurina/efeitos adversos , Dessensibilização Imunológica/efeitos adversos , Quimioterapia Combinada/efeitos adversos , Quimioterapia Combinada/métodos , Everolimo/administração & dosagem , Everolimo/efeitos adversos , Feminino , Glucocorticoides/administração & dosagem , Glucocorticoides/efeitos adversos , Rejeição de Enxerto/imunologia , Antígenos HLA/imunologia , Humanos , Imunossupressores/efeitos adversos , Isoanticorpos/imunologia , Masculino , Pessoa de Meia-Idade , Ácido Micofenólico/administração & dosagem , Ácido Micofenólico/efeitos adversos , Estudos Retrospectivos , Sirolimo/administração & dosagem , Sirolimo/efeitos adversos , Serina-Treonina Quinases TOR/imunologia , Tacrolimo/administração & dosagem , Tacrolimo/efeitos adversos , Resultado do Tratamento
3.
PLoS One ; 15(8): e0234396, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32756556

RESUMO

INTRODUCTION: Early conversion to a CNI-free immunosuppression with SRL was associated with an improved 1- and 3- yr renal function as compared with a CsA-based regimen in the SMART-Trial. Mixed results were reported on the occurrence of donor specific antibodies under mTOR-Is. Here, we present long-term results of the SMART-Trial. METHODS AND MATERIALS: N = 71 from 6 centers (n = 38 SRL and n = 33 CsA) of the original SMART-Trial (ITT n = 140) were enrolled in this observational, non-interventional extension study to collect retrospectively and prospectively follow-up data for the interval since baseline. Primary objective was the development of dnDSA. Blood samples were collected on average 8.7 years after transplantation. RESULTS: Development of dnDSA was not different (SRL 5/38, 13.2% vs. CsA 9/33, 27.3%; P = 0.097). GFR remained improved under SRL with 64.37 ml/min/1.73m2 vs. 53.19 ml/min/1.73m2 (p = 0.044). Patient survival did not differ between groups at 10 years. There was a trend towards a reduced graft failure rate (11.6% SRL vs. 23.9% CsA, p = 0.064) and less tumors under SRL (2.6% SRL vs. 15.2% CsA, p = 0.09). CONCLUSIONS: An early conversion to SRL did not result in an increased incidence of dnDSA nor increased long-term risk for the recipient. Transplant function remains improved with benefits for the graft survival.


Assuntos
Inibidores de Calcineurina/administração & dosagem , Imunossupressão/métodos , Imunossupressores/administração & dosagem , Transplante de Rim , Sirolimo/administração & dosagem , Adulto , Especificidade de Anticorpos , Esquema de Medicação , Feminino , Seguimentos , Taxa de Filtração Glomerular , Rejeição de Enxerto/etiologia , Rejeição de Enxerto/imunologia , Sobrevivência de Enxerto/imunologia , Humanos , Estimativa de Kaplan-Meier , Transplante de Rim/efeitos adversos , Transplante de Rim/mortalidade , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Serina-Treonina Quinases TOR/antagonistas & inibidores , Fatores de Tempo , Doadores de Tecidos
4.
Am Heart J ; 227: 111-117, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32739537

RESUMO

BACKGROUND: Complete revascularization in patients with an acute coronary syndrome and multivessel disease is superior compared to culprit-only treatment. However, it is unknown whether direct complete or staged complete revascularization should be pursued. METHODS: The BIOVASC study is an investigator-initiated, prospective, multicenter, randomized, 2-arm, international, open-label, noninferiority trial. We will randomize 1,525 patients 1:1 to immediate complete revascularization (experimental arm) or culprit-only plus staged complete revascularization (control arm). Patients will be enrolled in approximately 30 sites in Belgium, Italy, the Netherlands, and Spain. The primary end point is a composite of all-cause mortality, nonfatal myocardial infarction, any unplanned ischemia-driven revascularization (excluding staged procedures in the control arm at the predetermined time), and cerebrovascular events (MACCE) at 1 year post index procedure. CONCLUSIONS: The BIOVASC study aims to further refine the treatment algorithm for acute coronary syndrome patients with multivessel disease in terms of optimal timing for complete revascularization (Clinicaltrials.gov NCT03621501).


Assuntos
Síndrome Coronariana Aguda/tratamento farmacológico , Síndrome Coronariana Aguda/cirurgia , Stents Farmacológicos , Intervenção Coronária Percutânea , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Sirolimo/administração & dosagem , Implantes Absorvíveis , Estudos de Equivalência como Asunto , Humanos , Estudos Multicêntricos como Assunto , Polímeros , Estudos Prospectivos , Desenho de Prótese
5.
Brasília; CONITEC; jul. 2020. ilus, tab.
Não convencional em Português | BRISA/RedTESA | ID: biblio-1122908

RESUMO

INTRODUÇÃO: A LAM e uma doenca sistemica rara que esta associada a proliferacao das células musculares atipicas, podendo causar obstrucao de vias aereas e de vasos sanguineos nos pulmoes e, com o tempo, dificuldade de oxigenacao adequada do organismo. Ha dois tipos de LAM: a LAM esporadica (S-LAM, nao hereditaria) e a LAM associada a esclerose tuberosa (TSCLAM, hereditaria). Acomete principalmente mulheres em idade fertil, com uma prevalencia de cerca de 3 a 5 mulheres a cada 1 milhao. A causa da LAM esta associada a ativacao inadequada da sinalizacao alvo de rapamicina em mamiferos (mTOR -Mammalian Target of Rapamycin), que regula o crescimento celular e linfangiogenese. O tratamento se baseia no acompanhamento e tratamento das complicacoes e do acometimento pulmonar. O medicamento sirolimo, indicado para o tratamento de individuos com LAM, e um imunossupressor que inibe a proliferação celular e a producao de anticorpos alem de se ligar a uma proteina chamada mTOR, inibindo sua atividade, e assim suprimindo a proliferacao de celulas. PERGUNTA: Sirolimo e mais eficaz, seguro ou custo-efetivo para o tratamento de individuos com LAM quando comparado as opcoes ja disponiveis no SUS? EVIDÊNCIAS CIENTÍFICAS: A evidencia que subsidia o uso do sirolimo para tratamento de individuos com LAM se baseia em tres estudos de coorte, quatro ensaios clinicos e uma sub-analise de dados. Todos os estudos foram considerados como de baixa qualidade metodologica e alto risco de vies. Os estudos reportaram os resultados dos desfechos com diferentes formas e unidades de medidas, dificultando a interpretacao, sumarizacao e analise. Seis estudos reportaram que as alteracoes do volume expiratorio forcado em 1s (VEF1) foram menores nos pacientes durante o uso do sirolimo, em comparacao com placebo ou antes do uso. Apos 12 meses de tratamento com sirolimo foi observado melhora no VEF1, enquanto nos pacientes sem uso houve redução significativa de VEF1. Em relacao a capacidade vital forcada, quatro estudos reportaram melhora nos valores de pacientes que utilizaram sirolimo (p≤ 0,001). O desfecho qualidade de vida foi reportado por tres estudos, houve melhora da qualidade de vida dos pacientes utilizando sirolimo em dois estudos (p <0,05) e outro estudo nao observou diferencas estatisticamente significantes entre os grupos ao longo de 2 anos. Dos cinco estudos que reportaram dados sobre fator de crescimento endotelial vascular D, quatro observaram reducao significativa dos valores durante o tratamento com sirolimo (p< 0,05). Nos desfechos capacidade residual funcional, capacidade vital, volume residual e capacidade pulmonar total nao foram observadas diferenças clinicamente significativas entre sirolimo e placebo (p>0,05). As categorias mais frequentes de eventos adversos foram eventos gastrointestinais, infecciosos, pulmonares ou do trato respiratorio superior, dermatologico e neurologico. AVALIAÇÃO ECONÔMICA: O demandante apresentou uma analise de custo-utilidade (ACU) do uso de sirolimo em comparacao ao cuidado conservador no tratamento de pacientes com LAM, a analise resultou em incremento de custo de R$ 5.643,12 e ganho de 0,0985 anos de vida ajustados a qualidade, resultando em uma RCEI de R$ 57.290,55 por QALY ganho. A ACU apresenta incertezas, especialmente com relacao ao delineamento do modelo e utilizacao de valores de utilidades extraidas de um estudo que avaliou um subgrupo especifico de pacientes com LAM. AVALIAÇÃO DE IMPACTO ORÇAMENTÁRIO: A analise de impacto orcamentario resultou em orçamento incremental que variou de R$ 896,2 mil no primeiro ano da incorporacao a R$ 1,22 milhao no quinto ano. No acumulado de cinco anos, o impacto orcamentario incremental estimado foi de aproximadamente de R$ 5,3 milhoes. A analise esta subestimada devido as premissas adotadas para estimar a populacao. MONITORAMENTO DO HORIZONTE TECNOLÓGICO: Nao foram identificados medicamentos potenciais para o tratamento da linfangioleiomatose (LAM). RECOMENDAÇÃO PRELIMINAR: A Conitec, em sua 86a reuniao ordinaria, nos dias 04 e 05 de marco de 2020, recomendou que a materia fosse disponibilizada em consulta publica com recomendacao preliminar favoravel a ampliacao de uso, no SUS, do sirolimo para tratamento de individuos com LAM. CONSULTA PÚBLICA: Foram recebidas 1923 contribuicoes, 18 pelo formulario Tecnico-cientifico e 1905 pelo formulario de Experiencia e Opiniao, sendo 1902 (99%) concordantes com a recomendacao preliminar. O tema mais citado nas contribuicoes diz respeito a falta de alternativa terapeutica para tratamento de LAM. Muitas contribuicoes abordaram a melhora na qualidade de vida dos pacientes, a possibilidade de estabilizacao da LAM, melhora da função pulmonar e as dificuldades de acesso ao medicamento devido ao alto custo. RECOMENDAÇÃO FINAL: Foram discutidas e consideradas pelo plenario da Conitec a necessidade de incorporacao ao SUS de tratamento medicamentoso com acao direta na doenca, os beneficios clinicos do sirolimo na LAM, como diminuicao da progressao da doenca e as dificuldades de acesso devido ao alto custo do medicamento. Portanto, os presentes na 88ª reuniao ordinaria da Conitec, no dia 08 de julho de 2020, deliberaram, por unanimidade, recomendar a ampliacao de uso do sirolimo para tratamento de individuos adultos com LAM no Sistema Unico de Saude. DECISÃO: Ampliar o uso do sirolimo para o tratamento de individuos adultos com linfangioleiomiomatose (LAM), no ambito do Sistema Unico de Saude - SUS, conforme Protocolo do Ministerio da Saude, conforme Portaria no 24, publicada no Diario Oficial da Uniao no 149, secao 1, pagina 91, em 5 de agosto de 2020.


Assuntos
Humanos , Linfangioleiomiomatose/tratamento farmacológico , Sirolimo/administração & dosagem , Avaliação da Tecnologia Biomédica , Sistema Único de Saúde , Brasil , Análise Custo-Benefício/economia
6.
Gene ; 759: 144987, 2020 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-32712065

RESUMO

BACKGROUND: The immune response is influenced by the administration of omega-3 polyunsaturated fatty acids (PUFA). Multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE) are affected by PUFA. The combination of evening primrose/hemp seed oil (EPO/HSO) has essential fatty acids (EFAs) for human optimal health due to the favorable ratio of omega-6/omega-3 and antioxidantal properties. The study was conducted to evaluate the effects of EPO/HSO on improving the membrane fatty acids composition of spleen and blood cells and immunologic factors in compared to rapamycin (RAPA) in the EAE model. METHODS AND MATERIALS: Chronic-EAE was induced by induction of MOG in C57BL/6J mice (female, age: 6-8 weeks, weight 18-21). Mice were assigned to 5 groups (6/group) to evaluate the therapeutic effects of EPO/HSO supplement in comparison with rapamycin: A group; EPO/HSO + RAPA, B group; RAPA, C group; EPO/HSO. Results were compared to two control groups (EAE and naive). The fatty acid profile of the spleen and blood cell membrane was evaluated. Real-time-polymerase chain reaction was used for the evaluate the genes expression levels of interleukin (IL) -4, IL-5, and IL-13 in lymphocytes. Also, IL-4 of serum was evaluated by enzyme-linked immunosorbent assay (ELISA). RESULTS: Our findings indicated that EPO/HSO therapy significantly increased the percentage of essential fatty acids in cell membrane of the spleen and blood. The relative expression of IL-4, IL-5, and IL-13 genes in lymphocytes and serum level of IL-4 was significantly increased in the HSO/EPO treated group versus other groups. CONCLUSION: These results point to potential therapeutic effects on the repair of the structure of cell membranes and suppression of inflammation by EPO/HSO in EAE.


Assuntos
Antioxidantes/uso terapêutico , Encefalomielite Autoimune Experimental/tratamento farmacológico , Ácidos Graxos Essenciais/metabolismo , Fatores Imunológicos/uso terapêutico , Interleucinas/metabolismo , Óleos Vegetais/uso terapêutico , Sirolimo/uso terapêutico , Animais , Antioxidantes/administração & dosagem , Antioxidantes/farmacologia , Cannabis/química , Membrana Celular/efeitos dos fármacos , Membrana Celular/metabolismo , Suplementos Nutricionais , Combinação de Medicamentos , Feminino , Fatores Imunológicos/administração & dosagem , Fatores Imunológicos/farmacologia , Lipídeos de Membrana/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Óleos Vegetais/administração & dosagem , Primula/química , Sirolimo/administração & dosagem
7.
Int Heart J ; 61(4): 673-684, 2020 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-32684595

RESUMO

Hyperglycemia is an important risk factor for poor clinical outcomes in patients with acute myocardial infarction (AMI). The relative superiority of the long-term clinical outcomes of durable-polymer (DP) -based and biodegradable-polymer (BP) -based newer-generation drug-eluting stents (DESs) after successful percutaneous coronary intervention (PCI) in patients with AMI and prediabetes is not well established. We compared the clinical outcomes in such patients between DP-based and BP-based newer-generation DESs.A total of 4,377 patients with AMI and prediabetes were divided into the following two groups: the DP-DES group (n = 3,775; zotarolimus-eluting stents [ZES; n = 1,546] and everolimus-eluting stents [EES; n = 2,229]) and the BP-DES group (n = 602; biolimus-eluting stents [BES]). The primary endpoint was the occurrence of major adverse cardiac events (MACEs), defined as all-cause death, recurrent myocardial infarction (re-MI), or any repeat revascularization. The secondary endpoint was the occurrence of stent thrombosis (ST).The 2-year adjusted hazard ratio (aHR) of MACEs for ZES versus EES, ZES versus BES, EES versus BES, and ZES/EES versus BES (aHR: 1.125; 95% confidence interval [CI], 0.834-1.518; P = 0.440) were similar. The cumulative incidence of ST was also comparable between the DP-DES and BP-DES groups (aHR: 1.407; 95% CI, 0.476-4.158; P = 0.537). Moreover, the 2-year aHRs of all-cause death, CD, re-MI, target lesion revascularization (TLR), target vessel revascularization (TVR), and non-TVR were similar.Patients with AMI and prediabetes who received DP-DES or BP-DES during PCI showed comparable safety and efficacy during the 2-year follow-up period.


Assuntos
Implantes Absorvíveis/estatística & dados numéricos , Stents Farmacológicos/estatística & dados numéricos , Infarto do Miocárdio/cirurgia , Intervenção Coronária Percutânea/instrumentação , Estado Pré-Diabético/complicações , Idoso , Antineoplásicos/administração & dosagem , Everolimo/administração & dosagem , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/complicações , Sirolimo/administração & dosagem , Sirolimo/análogos & derivados
8.
Ann Hematol ; 99(8): 1771-1778, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32601796

RESUMO

Mantle cell lymphoma has a dismal prognosis at relapse or in the refractory setting. Among therapies, mTor pathway targeting by temsirolimus has been the first strategy approved for relapse in Europe. While its efficacy in monotherapy has long been demonstrated, its use remains limited. In the T3 phase Ib clinical trial, we investigated the recommended dose of temsirolimus in association with R-CHOP (R-CHOP-T), or high-dose cytarabine plus rituximab (R-DHA-T), or fludarabine, cyclophosphamide plus rituximab (R-FC-T). From November 11, 2011 to February 26, 2015, forty-one patients were enrolled. Patients presented with high MIPI (47.5%) at relapse and a median number of treatments of 1 (1-3). Patients were treated by R-CHOP-T (n = 10), R-FC-T (n = 14), or R-DHA-T (n = 17) according to the choice of local investigators. The maximum tolerated dose (MTD) was 15 mg in the R-CHOP-T arm and has not been determined in other treatment arms because of toxicities. All patients experienced ≥ Grade 3 adverse events, mainly thrombocytopenia (76%). Twenty-six patients discontinued prematurely the treatment, mostly for toxicity (n = 12) and progression of the disease (n = 8). Of note, 6 patients of the R-DHA-T arm reached complete remission (35%). Temsirolimus with immuno-chemotherapy is associated with a high rate of toxicities. Determination of MTD could only be achieved for R-CHOP-T arm. Associations between temsirolimus and other targeted therapies may be warranted for R/R MCL patients.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Imunoterapia , Linfoma de Célula do Manto/terapia , Sirolimo/análogos & derivados , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Ciclofosfamida/administração & dosagem , Ciclofosfamida/efeitos adversos , Intervalo Livre de Doença , Doxorrubicina/administração & dosagem , Doxorrubicina/efeitos adversos , Feminino , Humanos , Linfoma de Célula do Manto/mortalidade , Masculino , Pessoa de Meia-Idade , Prednisona/administração & dosagem , Prednisona/efeitos adversos , Rituximab/administração & dosagem , Rituximab/efeitos adversos , Sirolimo/administração & dosagem , Sirolimo/efeitos adversos , Taxa de Sobrevida , Trombocitopenia/induzido quimicamente , Trombocitopenia/mortalidade , Vincristina/administração & dosagem , Vincristina/efeitos adversos
9.
J Endovasc Ther ; 27(5): 683-690, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32666871

RESUMO

Purpose: To evaluate the safety and efficacy of the novel SELUTION sustained-limus-release (SLR) drug-eluting balloon (DEB) in the treatment of femoropopliteal lesions. Materials and Methods: Between October 2016 and May 2017, 50 subjects (mean age 69.6±10.4 years; 29 men) with symptomatic moderate to severe lower limb ischemia (Rutherford categories 2 or 3) were enrolled at 4 German centers for the SELUTION SLR first-in-human trial (ClinicalTrials.gov NCT02941224). The SELUTION SLR utilizes micro-reservoirs (biodegradable polymer spheres containing sirolimus) embedded within an amphipathic membrane coated onto an angioplasty balloon. The biodegradable reservoirs are transferred to the target vessel lumen during brief balloon inflation. The primary trial objective was comparison of angiographic late lumen loss at 6 months against an objective performance criterion (OPC) value of 1.04 mm for uncoated balloon angioplasty. Secondary endpoints included device, procedural, and clinical success; clinical and imaging assessments of primary patency and restenosis; functional assessments including Rutherford category and ankle-brachial index (ABI); and major adverse events [composite of cardiovascular mortality, index limb amputation, target limb thrombosis, and clinically-driven target lesion revascularization (CD-TLR)]. Results: At 6 months, median angiographic late lumen loss following SELUTION SLR treatment was 0.19 mm (range -1.16 to 3.07). Mean angiographic late lumen loss (n=34) was 0.29±0.84 mm (95% CI -0.01 to 0.58), significantly lower than the 1.04-mm OPC value (p<0.001). The rate of primary patency by duplex ultrasound was 88.4%, and freedom from angiographic binary restenosis was 91.2%. Through 6 months, there was significant improvement over baseline in Rutherford categories (p<0.001) and in ABI measurements (p<0.001). A single case (2%) of CD-TLR occurred at 5 months. There were no other major adverse events. Conclusion: Through 6 months, the SELUTION SLR DEB appears to inhibit restenosis effectively and safely, improving outcomes in subjects with symptomatic femoropopliteal disease.


Assuntos
Angioplastia com Balão/instrumentação , Fármacos Cardiovasculares/administração & dosagem , Materiais Revestidos Biocompatíveis , Artéria Femoral , Isquemia/terapia , Doença Arterial Periférica/terapia , Artéria Poplítea , Sirolimo/administração & dosagem , Idoso , Idoso de 80 Anos ou mais , Angioplastia com Balão/efeitos adversos , Fármacos Cardiovasculares/efeitos adversos , Constrição Patológica , Preparações de Ação Retardada , Feminino , Artéria Femoral/diagnóstico por imagem , Artéria Femoral/fisiopatologia , Alemanha , Humanos , Isquemia/diagnóstico por imagem , Isquemia/fisiopatologia , Salvamento de Membro , Masculino , Pessoa de Meia-Idade , Doença Arterial Periférica/diagnóstico por imagem , Doença Arterial Periférica/fisiopatologia , Artéria Poplítea/diagnóstico por imagem , Artéria Poplítea/fisiopatologia , Estudos Prospectivos , Recuperação de Função Fisiológica , Índice de Gravidade de Doença , Sirolimo/efeitos adversos , Fatores de Tempo , Resultado do Tratamento , Grau de Desobstrução Vascular
10.
Int J Nanomedicine ; 15: 3771-3790, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32547027

RESUMO

Introduction: Rapamycin has been considered as a potential treatment for osteoarthritis (OA). Drug carriers fabricated from liposomes can prolong the effects of drugs and reduce side effects of drugs. Low-intensity pulsed ultrasound (LIPUS) has been found to possess anti-OA effects. Materials and Methods: The anti-osteoarthritic effects of liposome-encapsulated rapamycin (L-rapa) combined with LIPUS were examined by culture of normal and OA chondrocytes in alginate beads and further validated in OA prone Dunkin-Hartley guinea pigs. Results: L-rapa with LIPUS largely up-regulated aggrecan and type II collagen mRNA in human OA chondrocytes (HOACs). L-rapa with LIPUS caused significant enhancement in proteoglycan and type II collagen production in HOACs. Large decreases in both MMP-13 and IL-6 proteins were found in the HOACs exposed to L-rapa with LIPUS. Intra-articular injection of 40 µL L-rapa at both 5 µM and 50 µM twice a week combined with LIPUS thrice a week for 8 weeks significantly increased GAGs and type II collagen in the cartilage of knee. Results on OARSI score showed that intra-articular injection of 5 µM L-rapa with LIPUS displayed the greatest anti-OA effects. Immunohistochemistry revealed that L-rapa with or without LIPUS predominantly reduced MMP-13 in vivo. The values of complete blood count and serum biochemical examinations remained in the normal ranges after the injections with or without LIPUS. These data indicated that intra-articular injection of L-rapa collaborated with LIPUS is not only effective against OA but a safe OA therapy. Conclusion: Taken together, L-rapa combined with LIPUS possessed the most consistently and effectively anabolic and anti-catabolic effects in HOACs and the spontaneous OA guinea pigs. This study evidently revealed that liposome-encapsulation collaborated with LIPUS is able to reduce the effective dose and administration frequency of rapamycin and further stably reinforce its therapeutic actions against OA.


Assuntos
Osteoartrite/terapia , Sirolimo/uso terapêutico , Ondas Ultrassônicas , Animais , Peso Corporal/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/efeitos da radiação , Células Cultivadas , Condrócitos/efeitos dos fármacos , Condrócitos/patologia , Condrócitos/efeitos da radiação , Colágeno Tipo II/metabolismo , Liberação Controlada de Fármacos , Cobaias , Humanos , Injeções Intra-Articulares , Interleucina-6/metabolismo , Lipossomos/ultraestrutura , Masculino , Metaloproteinase 13 da Matriz/metabolismo , Pessoa de Meia-Idade , Osteoartrite/sangue , Osteoartrite/patologia , Proteoglicanas/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Sirolimo/administração & dosagem , Sirolimo/farmacologia
11.
Medicine (Baltimore) ; 99(23): e20669, 2020 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-32502056

RESUMO

RATIONALE: It is very difficult to treat patients with aplastic anemia accompanied by chronic kidney disease. The nephrotoxicity of cyclosporine limits its use in these patients. Most of these patients also lack suitable sibling donors. Sirolimus, as a new type of immunosuppressive agent, has good therapeutic effect, lower toxicity, especially lower nephrotoxicity, thus attracting the attention of hematologists. PATIENT CONCERNS: This 55-year-old Chinese male patient suffered from pancytopenia and renal insufficiency and has a poor quality of life. DIAGNOSIS: The patient was diagnosed as severe aplastic anemia with chronic kidney disease-G3a. INTERVENTIONS: We started the sirolimus therapy with the initial dose of 1 mg per day. Based on the good tolerability and clinical effect, we increased the dose of sirolimus to 2 mg per day after 2 weeks. OUTCOMES: By taking sirolimus, the patient's peripheral blood cell count gradually increased, and he achieved blood transfusion independent, and eventually the blood cell count was completely normal. LESSONS: We consider that sirolimus is a safe, effective, and well-tolerated oral drug that can be used as a treatment for aplastic anemia patients with chronic kidney disease.


Assuntos
Anemia Aplástica/tratamento farmacológico , Imunossupressores/administração & dosagem , Insuficiência Renal Crônica/tratamento farmacológico , Sirolimo/administração & dosagem , Administração Oral , Anemia Aplástica/complicações , Humanos , Masculino , Pessoa de Meia-Idade , Insuficiência Renal Crônica/complicações
12.
JAMA ; 323(23): 2407-2416, 2020 06 16.
Artigo em Inglês | MEDLINE | ID: mdl-32543684

RESUMO

Importance: Discontinuing aspirin after short-term dual antiplatelet therapy (DAPT) was evaluated as a bleeding reduction strategy. However, the strategy of ticagrelor monotherapy has not been exclusively evaluated in patients with acute coronary syndromes (ACS). Objective: To determine whether switching to ticagrelor monotherapy after 3 months of DAPT reduces net adverse clinical events compared with ticagrelor-based 12-month DAPT in patients with ACS treated with drug-eluting stents. Design, Setting, and Participants: A randomized multicenter trial was conducted in 3056 patients with ACS treated with drug-eluting stents between August 2015 and October 2018 at 38 centers in South Korea. Follow-up was completed in October 2019. Interventions: Patients were randomized to receive ticagrelor monotherapy (90 mg twice daily) after 3-month DAPT (n = 1527) or ticagrelor-based 12-month DAPT (n = 1529). Main Outcomes and Measures: The primary outcome was a 1-year net adverse clinical event, defined as a composite of major bleeding and adverse cardiac and cerebrovascular events (death, myocardial infarction, stent thrombosis, stroke, or target-vessel revascularization). Prespecified secondary outcomes included major bleeding and major adverse cardiac and cerebrovascular events. Results: Among 3056 patients who were randomized (mean age, 61 years; 628 women [20%]; 36% ST-elevation myocardial infarction), 2978 patients (97.4%) completed the trial. The primary outcome occurred in 59 patients (3.9%) receiving ticagrelor monotherapy after 3-month DAPT and in 89 patients (5.9%) receiving ticagrelor-based 12-month DAPT (absolute difference, -1.98% [95% CI, -3.50% to -0.45%]; hazard ratio [HR], 0.66 [95% CI, 0.48 to 0.92]; P = .01). Of 10 prespecified secondary outcomes, 8 showed no significant difference. Major bleeding occurred in 1.7% of patients with ticagrelor monotherapy after 3-month DAPT and in 3.0% of patients with ticagrelor-based 12-month DAPT (HR, 0.56 [95% CI, 0.34 to 0.91]; P = .02). The incidence of major adverse cardiac and cerebrovascular events was not significantly different between the ticagrelor monotherapy after 3-month DAPT group (2.3%) vs the ticagrelor-based 12-month DAPT group (3.4%) (HR, 0.69 [95% CI, 0.45 to 1.06]; P = .09). Conclusions and Relevance: Among patients with acute coronary syndromes treated with drug-eluting stents, ticagrelor monotherapy after 3 months of dual antiplatelet therapy, compared with ticagrelor-based 12-month dual antiplatelet therapy, resulted in a modest but statistically significant reduction in a composite outcome of major bleeding and cardiovascular events at 1 year. The study population and lower than expected event rates should be considered in interpreting the trial. Trial Registration: ClinicalTrials.gov Identifier: NCT02494895.


Assuntos
Síndrome Coronariana Aguda/tratamento farmacológico , Aspirina/uso terapêutico , Doenças Cardiovasculares/prevenção & controle , Hemorragia/induzido quimicamente , Inibidores da Agregação de Plaquetas/uso terapêutico , Ticlopidina/uso terapêutico , Síndrome Coronariana Aguda/terapia , Aspirina/efeitos adversos , Doenças Cardiovasculares/epidemiologia , Quimioterapia Combinada , Stents Farmacológicos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Intervenção Coronária Percutânea , Inibidores da Agregação de Plaquetas/efeitos adversos , Sirolimo/administração & dosagem , Ticlopidina/efeitos adversos
13.
Oncol Res Treat ; 43(7-8): 333-339, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32541143

RESUMO

BACKGROUND: Non-clear cell renal cell cancers (nccRCC) are rare entities, and the optimal therapy in metastatic disease has still to be defined. METHODS: In this small prospectively randomized phase IIa multicenter trial, we investigated temsirolimus (TEM) versus sunitinib (SUN) as first-line therapy in patients with metastatic nccRCC. The patients were randomized 1:1 to either TEM in a dose of 25 mg i.v. once a week or SUN with 50 mg p.o. daily for 4 weeks on and 2 weeks off. Primary endpoint was progression-free survival (PFS). In total, 22 patients were included with predominantly papillary RCC (16/22) followed by chromophobe RCC and others. RESULTS: The male to female ratio was 16:6. The tumor control rate (CR + PR + SD) was 58% for TEM and 90% for SUN-treated patients. There was also a trend for improved PFS with 9.3 versus 13.2 months (HR 1.64; 95% CI 0.65-4.18) in favor of SUN. There was no trend for overall survival. CONCLUSIONS: Despite this trial had to be terminated earlier due to low recruitment, the results match the other studies published so far with the mTOR inhibitor everolimus and SUN, which show a trend in favor of SUN for ORR and PFS.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células Renais/tratamento farmacológico , Neoplasias Renais/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Renais/patologia , Feminino , Humanos , Agências Internacionais , Neoplasias Renais/patologia , Masculino , Pessoa de Meia-Idade , Sirolimo/administração & dosagem , Sirolimo/análogos & derivados , Sociedades Médicas , Sunitinibe/administração & dosagem , Taxa de Sobrevida , Resultado do Tratamento , Adulto Jovem
14.
JACC Cardiovasc Interv ; 13(9): 1100-1109, 2020 05 11.
Artigo em Inglês | MEDLINE | ID: mdl-32381186

RESUMO

OBJECTIVES: The aim of this study was to assess 2-year safety and efficacy of the current-generation thin composite-wire-strut durable-polymer Resolute Onyx zotarolimus-eluting stent (ZES), compared with the ultrathin-strut biodegradable-polymer Orsiro sirolimus-eluting stent (SES) in all-comers and a pre-specified small-vessel subgroup analysis. BACKGROUND: The Resolute Onyx ZES is widely used in clinical practice, but no follow-up data beyond 1 year have been published. The randomized BIONYX (Bioresorbable Polymer-Coated Orsiro Versus Durable Polymer-Coated Resolute Onyx Stents) trial (NCT02508714) established the noninferiority of ZES versus SES regarding target vessel failure (TVF) rates. METHODS: A total of 2,488 all-comer patients were treated at 7 coronary intervention centers in Belgium, Israel, and the Netherlands. The main endpoint, TVF, was a composite of safety (cardiac death or target vessel-related myocardial infarction) and efficacy (clinically indicated target vessel revascularization). Two-year follow-up data were analyzed using Kaplan-Meier methods. RESULTS: Two-year follow-up data were available for 2,460 of 2,488 patients (98.9%). TVF occurred in 93 of 1,243 patients (7.6%) assigned to ZES versus 87 of 1,245 patients (7.1%) assigned to SES (log-rank p = 0.66). There was no significant between-stent difference in individual components of this endpoint. The incidence of definite-or-probable stent thrombosis was low for both treatment arms (0.4% vs. 1.1%; log-rank p = 0.057). In patients stented in small vessels, there was no between-stent difference (TVF 8.2% vs. 8.7% [log-rank p = 0.75], target lesion revascularization 4.0% vs. 4.4% [log-rank p = 0.77]). CONCLUSIONS: At 2-year follow-up, the novel thin composite-wire-strut durable-polymer Resolute Onyx ZES showed in all-comers similar safety and efficacy compared with the ultrathin cobalt-chromium-strut biodegradable-polymer Orsiro SES. The analysis of patients who were treated in small vessels also suggested no advantage for either stent.


Assuntos
Fármacos Cardiovasculares/administração & dosagem , Doença da Artéria Coronariana/terapia , Stents Farmacológicos , Intervenção Coronária Percutânea/instrumentação , Sirolimo/análogos & derivados , Idoso , Bélgica , Fármacos Cardiovasculares/efeitos adversos , Doença da Artéria Coronariana/diagnóstico por imagem , Trombose Coronária/etiologia , Feminino , Humanos , Israel , Masculino , Pessoa de Meia-Idade , Países Baixos , Intervenção Coronária Percutânea/efeitos adversos , Estudos Prospectivos , Desenho de Prótese , Sirolimo/administração & dosagem , Sirolimo/efeitos adversos , Fatores de Tempo , Resultado do Tratamento
15.
Medicine (Baltimore) ; 99(19): e19763, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32384426

RESUMO

INTRODUCTION: Pendred syndrome (PDS)/DFNB 4 is a disorder with fluctuating and progressive hearing loss, vertigo, and thyroid goiter. We identified pathophysiology of a neurodegenerative disorder in PDS patient derived cochlear cells that were induced via induced pluripotent stem cells and found sirolimus, an mTOR inhibitor, as an inhibitor of cell death with the minimum effective concentration less than 1/10 of the approved dose for other diseases. Given that there is no rational standard therapy for PDS, we planned a study to examine effects of low dose oral administration of sirolimus for the fluctuating and progressive hearing loss, and the balance disorder of PDS by daily monitor of their audio-vestibular symptoms. METHODS AND ANALYSIS: This is a phase I/IIa double blind parallel-group single institute trial in patient with PDS/DFNB4. Sixteen of outpatients with fluctuating hearing diagnosed as PDS in SLC26A4 genetic testing aged in between 7 and 50 years old at the time of consent are given either placebo or sirolimus tablet (NPC-12T). In NPC-12T placebo arm, placebo will be given for 36 weeks; in active substance arm, placebo will be given for 12 weeks and the NPC-12T for 24 weeks. Primary endpoints are safety and tolerability. The number of occurrences and types of adverse events and of side effects will be sorted by clinical symptoms and by abnormal change of clinical test results. A 2-sided 95% confidence interval of the incidence rate by respective dosing arms will be calculated using the Clopper-Pearson method. Clinical effects on audio-vestibular tests performed daily and precise physiological test at each visit will also be examined as secondary and expiratory endpoints. TRIAL REGISTRATION NUMBER: JMA-IIA00361; Pre-results.


Assuntos
Bócio Nodular/tratamento farmacológico , Perda Auditiva Neurossensorial/tratamento farmacológico , Sirolimo/administração & dosagem , Aqueduto Vestibular/anormalidades , Adolescente , Adulto , Audiometria , Criança , Método Duplo-Cego , Feminino , Bócio Nodular/genética , Perda Auditiva Neurossensorial/genética , Humanos , Masculino , Pessoa de Meia-Idade , Transportadores de Sulfato/genética , Resultado do Tratamento , Testes de Função Vestibular , Adulto Jovem
16.
Life Sci ; 253: 117747, 2020 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-32376270

RESUMO

AIMS: Multiple sclerosis (MS) whose pathogenesis is still unclear is a chronic progressive disease in the central nervous system. Gut microbiota can directly or indirectly affect the immune system through the brain gut axis to engage in the occurrence and development of the disease. MATERIALS AND METHODS: C57BL/6 mice which were immunized by MOG35-55 to prepare experimental autoimmune encephalomyelitis (EAE) animal models were treated with rapamycin and MCC950 (CP-456773) in combination or separately. After sequencing the 16S rRNA V4 region of gut microbiota, the species, abundance and composition of gut microbiota were analyzed by Alpha diversity, Bata diversity and LEfSe analysis. The pathological changes and the expression of CD4 and CD8 of brain, large intestine and spleen were detected. KEY FINDINGS: The results showed that rapamycin and MCC950 could alleviate the progression of the disease by inducing autophagy and inhibiting the immune response. The Alpha diversity of EAE model group was no significant difference compering to control group while the number of OTUs was decreased. After the treatment by rapamycin and MCC950, the abundance and composition of gut microbiota was relatively recovered, which was close to that of normal mice. SIGNIFICANCE: Inhibiting immune cell-mediated inflammation and restoring the composition of gut microbiota may help to alleviate the clinical symptoms of multiple sclerosis. Furthermore, to research the regulatory effect between immune response and gut microbiota may be a new strategy for the prevention and treatment of multiple sclerosis.


Assuntos
Encefalomielite Autoimune Experimental/tratamento farmacológico , Furanos/farmacologia , Microbioma Gastrointestinal/imunologia , Esclerose Múltipla/tratamento farmacológico , Sirolimo/farmacologia , Sulfonamidas/farmacologia , Animais , Encéfalo/imunologia , Encéfalo/fisiopatologia , Modelos Animais de Doenças , Progressão da Doença , Encefalomielite Autoimune Experimental/imunologia , Encefalomielite Autoimune Experimental/microbiologia , Feminino , Furanos/administração & dosagem , Inflamação/imunologia , Inflamação/patologia , Intestino Grosso/imunologia , Intestino Grosso/patologia , Camundongos , Camundongos Endogâmicos C57BL , Esclerose Múltipla/imunologia , Esclerose Múltipla/microbiologia , RNA Ribossômico 16S , Sirolimo/administração & dosagem , Baço/imunologia , Baço/patologia , Sulfonamidas/administração & dosagem
18.
JACC Cardiovasc Interv ; 13(7): 820-830, 2020 04 13.
Artigo em Inglês | MEDLINE | ID: mdl-32273094

RESUMO

OBJECTIVES: The aim of this study was to determine 1-year safety and efficacy after treatment with the COMBO and Orsiro stents. BACKGROUND: The COMBO stainless-steel stent has an anti-CD34+ antibody coating to capture endothelial progenitor cells, thereby promoting faster endothelialization. The Orsiro is an ultrathin-strut cobalt-chromium stent, covered by an extremely thin layer of amorphous silicon carbide to minimize ion leakage. Both devices elute sirolimus from biodegradable polymers. METHODS: For this analysis we included European patients from the COMBO collaboration, a patient-level pooling of 2 prospective all-comers registries of COMBO stent implantation (n = 2,775), and all patients randomized to the Orsiro stent (n = 1,169) from the Dutch BIO-RESORT (Comparison of Biodegradable Polymer and Durable Polymer Drug-Eluting Stents in an All Comers Population) randomized trial. The main outcome of interest was 1-year target lesion failure, a composite of cardiac death, target vessel myocardial infarction, and clinically driven target lesion revascularization evaluated using propensity score-matched analysis. RESULTS: At baseline, COMBO patients were older and had more insulin-treated diabetes, renal insufficiency, and other comorbidities. However, Orsiro patients included more current smokers and more acute coronary syndrome presentations. Orsiro patients also received longer stents and had more complex target lesions. After propensity score-matched analysis (n = 862/arm), 1-year target lesion failure occurred in 4.1% of COMBO-treated and 2.7% of Orsiro-treated patients (hazard ratio: 1.55; 95% confidence interval: 0.92 to 2.62; p = 0.10). Definite stent thrombosis occurred in 0.5% of COMBO-treated and 0.5% of Orsiro-treated patients (p = 0.99). CONCLUSIONS: A propensity score-matched comparison of all comers treated with the COMBO or Orsiro stent showed no statistically significant differences. Stent thrombosis risk was low and similar between the stents. (Comparison of Biodegradable Polymer and Durable Polymer Drug-Eluting Stents in an All Comers Population [BIO-RESORT], NCT01674803; MASCOT-Post Marketing Registry [MASCOT], NCT02183454; Prospective Registry to Assess the Long-term Safety and Performance of the Combo Stent [REMEDEE Reg], NCT01874002).


Assuntos
Implantes Absorvíveis , Fármacos Cardiovasculares/administração & dosagem , Doença da Artéria Coronariana/terapia , Stents Farmacológicos , Intervenção Coronária Percutânea/instrumentação , Polímeros/química , Sirolimo/administração & dosagem , Idoso , Fármacos Cardiovasculares/efeitos adversos , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/mortalidade , Trombose Coronária/etiologia , Bases de Dados Factuais , Europa (Continente) , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Intervenção Coronária Percutânea/efeitos adversos , Intervenção Coronária Percutânea/mortalidade , Pontuação de Propensão , Desenho de Prótese , Ensaios Clínicos Controlados Aleatórios como Assunto , Sistema de Registros , Medição de Risco , Fatores de Risco , Sirolimo/efeitos adversos , Fatores de Tempo , Resultado do Tratamento
20.
Medicina (Kaunas) ; 56(3)2020 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-32121323

RESUMO

Background and Objectives: Little is known about the upfront two-stent strategy (U2SS) for true coronary bifurcation lesions (CBLs) in acute coronary syndrome (ACS). We aimed to present our two-year follow-up results on the U2SS by using different two-stent techniques for the true CBL with a large side branch (SB) in ACS patients, including unstable angina (UA), non-ST-segment elevation myocardial infarction (NSTEMI), and ST-segment elevation myocardial infarction (STEMI), and to identify independent predictors of the presence of major adverse cardiac events (MACEs) after intervention. Materials and Methods: The study included 201 consecutive ACS patients with true CBLs who underwent percutaneous coronary intervention (PCI) using U2SS from October 2015 to March 2018. Clinical outcomes at follow-up were assessed. MACE was defined as a composite of cardiac death, non-fatal myocardial infarction, and target lesion revascularization (TLR). Results: 31.3% of the patients had an UA, 46.3% had an NSTEMI, and 22.4% had an STEMI. CBL was most frequently located in the left anterior descending (LAD)/diagonal artery (59.2%). In total, 71.1% of the patients had a Medina classification (1,1,1). Overall, 62.2% of cases were treated with mini-crush stenting. Clopidogrel was given in 23.9% of the patients; 71.1% of the patients received everolimus eluting stent (EES); and 11.9% received a sirolimus eluting stent (SES). Final kissing balloon inflation was carried out in all patients, with an unsatisfactory rate of 5%. A proximal optimization technique sequence was successfully carried out in all patients. The MACE incidence was 16.9% with a median follow-up period of 2.1 years. There were seven cardiac deaths (3.5%). The TLR rate was 13.4% (n = 27), with PCI treatment in 16 patients, and coronary artery bypass grafting treatment in 11 patients. After multivariate penalized logistic regression analysis (Firth logistic regression), clopidogrel use (odds ratio (OR): 2.19; 95% confidence interval (CI): 0.41-2.51; p = 0.007) and SES use (OR: 1.86; 95% CI: 0.31-2.64; p = 0.014) were independent predictors of the presence of MACE. Conclusion: U2SS is feasible and safe for the true CBLs with large and diseased SB in ACS patients, and is related to a relatively low incidence of MACE. Clopidogrel use and SES use may predict the MACE development in ACS patients treated using U2SS.


Assuntos
Síndrome Coronariana Aguda/terapia , Stents Farmacológicos , Isquemia Miocárdica/terapia , Intervenção Coronária Percutânea/mortalidade , Síndrome Coronariana Aguda/complicações , Síndrome Coronariana Aguda/mortalidade , Idoso , Angina Instável/etiologia , Angina Instável/mortalidade , Angina Instável/terapia , Clopidogrel/administração & dosagem , Everolimo/administração & dosagem , Estudos de Viabilidade , Feminino , Seguimentos , Humanos , Incidência , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Isquemia Miocárdica/etiologia , Isquemia Miocárdica/mortalidade , Infarto do Miocárdio sem Supradesnível do Segmento ST/etiologia , Infarto do Miocárdio sem Supradesnível do Segmento ST/mortalidade , Infarto do Miocárdio sem Supradesnível do Segmento ST/terapia , Estudos Retrospectivos , Infarto do Miocárdio com Supradesnível do Segmento ST/etiologia , Infarto do Miocárdio com Supradesnível do Segmento ST/mortalidade , Infarto do Miocárdio com Supradesnível do Segmento ST/terapia , Sirolimo/administração & dosagem , Resultado do Tratamento
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