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Background: Pulmonary arterial hypertension (PAH), defined as the presence of a mean pulmonary artery pressure > 20 mmHg, pulmonary artery wedge pressure ≤ 15 mmHg, and pulmonary vascular resistance (PVR) > 2 Wood units based on expert consensus, is characterized by a progressive and sustained increase in PVR, which may lead to right heart failure and death. PAH is a well-known complication of connective tissue diseases (CTDs), such as systemic sclerosis, systemic lupus erythematosus, Sjogren's syndrome, and other autoimmune conditions. In the past few years, tremendous progress in the understanding of PAH pathogenesis has been made, with various novel diagnostic and screening methods for the early detection of PAH proposed worldwide. Objectives: This study aimed to obtain a comprehensive understanding and provide recommendations for the management of CTD-PAH in Taiwan, focusing on its clinical importance, prognosis, risk stratification, diagnostic and screening algorithm, and pharmacological treatment. Methods: The members of the Taiwan Society of Cardiology (TSOC) and Taiwan College of Rheumatology (TCR) reviewed the related literature thoroughly and integrated clinical trial evidence and real-world clinical experience for the development of this consensus. Conclusions: Early detection by regularly screening at-risk patients with incorporations of relevant autoantibodies and biomarkers may lead to better outcomes of CTD-PAH. This consensus proposed specific screening flowcharts for different types of CTDs, the risk assessment tools applicable to the clinical scenario in Taiwan, and a recommendation of medications in the management of CTD-PAH.
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The lung is the first and most frequent organ to fail among sepsis patients. The mortality rate of sepsis-related acute lung injury (ALI) is high. Despite appropriate antimicrobial therapy, no treatment strategies are available for sepsis-induced ALI. Stem cell-mediated paracrine signaling is a potential treatment method for various diseases. This study aimed to examine the effects of induced pluripotent stem cell-derived conditioned medium (iPSC-CM) combined with antibiotics on ALI in a rat model of Escherichia coli-induced sepsis. Rats were administered either iPSC-CM or the vehicle (saline) with antibiotics (ceftriaxone). After 72 h, liquid biopsy, bronchoalveolar lavage fluid (BALF), and tissues were harvested for analysis. Survival rates were observed for up to 3 days. Furthermore, we examined the effects of iPSC-CM on cytokine production, metalloproteinase 9 (MMP-9) expression, and NLRP3-ASC interaction in RAW264.7 cells stimulated with lipopolysaccharide/interferon-γ (LPS/IFN-γ). Combined treatment of iPSC-CM with antibiotics significantly improved survival in E. coli-infected rats (p = 0.0006). iPSC-CM ameliorated E. coli-induced infiltration of macrophages, reducing the number of cells in BALF, and suppressing interleukin (IL)-1ß, MIP-2, IL-6, and MMP-9 messenger RNA in lung sections. iPSC-CM treatment attenuated NLRP3 expression and inhibited NLRP3 inflammasome activation by disrupting NLRP3-mediated ASC complex formation in LPS/IFN-γ-primed RAW264.7 cells. This study reveals the mechanisms underlying iPSC-CM-conferred anti-inflammatory activity in ALI through the attenuation of macrophage recruitment to the lung, thus inactivating NLRP3 inflammasomes in macrophages. iPSC-CM therapy may be a useful adjuvant treatment to reduce sepsis-related mortality by ameliorating ALI.
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Lesão Pulmonar Aguda , Células-Tronco Pluripotentes Induzidas , Sepse , Lesão Pulmonar Aguda/induzido quimicamente , Animais , Antibacterianos/efeitos adversos , Ceftriaxona/efeitos adversos , Meios de Cultivo Condicionados/farmacologia , Escherichia coli/metabolismo , Humanos , Células-Tronco Pluripotentes Induzidas/metabolismo , Inflamassomos/metabolismo , Lipopolissacarídeos/farmacologia , Metaloproteinase 9 da Matriz , Camundongos , Camundongos Endogâmicos C57BL , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Ratos , Sepse/tratamento farmacológicoRESUMO
Warfarin is an alternate choice for patients who are not eligible for non-vitamin K oral anticoagulants after acute myocardial infarction (AMI). This study aimed to compare the long-term outcome of triple antithrombotic therapy (TAT) with that of dual antiplatelet therapy (DAPT) after AMI. This was a nationwide, propensity score-matched, case-control study of 186,112 first AMI patients, of whom 2,825 received TAT comprising aspirin, clopidogrel, and warfarin. Propensity score matching in a ratio of 1:4 by age, sex, comorbidities, and treatment was adopted, Finally, 2,813 AMI patients and 11,252 matched controls that were administered TAT and DAPT (aspirin and clopidogrel), respectively, were included in our analysis. The 12-year overall survival rate did not differ between both strategies (P = .3167). TAT was beneficial in old age (hazard ratio [HR] = 0.92), female sex (HR = 0.86), atrial fibrillation (AF) (HR = 0.80), hypertension (HR = 0.92), cerebrovascular accident (HR = 0.90), and in the absence of percutaneous coronary intervention (HR = 0.79). TAT reduced the rate of recurrent myocardial infarction (P = .0108) but did not affect the rate of stroke (P = .4867), gastrointestinal bleeding (P = .3889), or intracranial hemorrhage (ICH) (P = .3449). TAT reduces the incidence of recurrent myocardial infarction and does not increase the risk of major bleeding, while compared to DAPT.
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Terapia Antiplaquetária Dupla/métodos , Fibrinolíticos/administração & dosagem , Infarto do Miocárdio/tratamento farmacológico , Inibidores da Agregação Plaquetária/administração & dosagem , Terapia Trombolítica/métodos , Idoso , Relação Dose-Resposta a Droga , Quimioterapia Combinada , Feminino , Seguimentos , Humanos , Masculino , Estudos Retrospectivos , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: Use of statin has been associated with reduced risk of cardiovascular diseases events and mortality. However, in patients with end-stage renal disease (ESRD), the protective effects of statin are controversial. To evaluate the impact of chronic statin use on clinical outcomes of patients with acute myocardial infarction (AMI) with ESRD. METHODS: We enrolled 8056 patients with ESRD who were initially diagnosed and admitted for first AMI from Taiwan's National Health Insurance Research Database. Of which, 2134 patients underwent statin therapy. We randomly selected and use age, sex, hypertension, diabetes mellitus (DM), peripheral vascular diseases (PVD), heart failure (HF), cerebrovascular accidents (CVA), chronic obstructive pulmonary disease, matched with the study group as controls (non-stain user). We compared the effects of statin use in term of all-cause death among patients with AMI with ESRD. RESULTS: Statin use resulted in a significantly higher survival rate in patients ith AMI with ESRD compared with non-statin users. After adjusted the comorbidities the male patients and patients with DM, PVD, HF and CVA had lower long-term survival rate (all p<0.001). Patients who underwent percutaneous coronary intervention (p<0.001), ACE inhibitors/angiotensin II receptor blockers (p<0.001), ß receptor blockers (p<0.001) and statin therapy (p=0.007) had better long-term survival rate. Patients with AMI with ESRD on statin therapy exhibited a significantly lower risk of mortality compared with non-statin users (p<0.0001). CONCLUSION: Among patients with ESRD with AMI, statin therapy was associated with reduced all-cause mortality.
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Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Falência Renal Crônica , Infarto do Miocárdio , Fármacos Cardiovasculares/uso terapêutico , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/prevenção & controle , Estudos de Casos e Controles , Causas de Morte , Comorbidade , Feminino , Humanos , Falência Renal Crônica/epidemiologia , Falência Renal Crônica/terapia , Masculino , Pessoa de Meia-Idade , Mortalidade , Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/mortalidade , Substâncias Protetoras/uso terapêutico , Fatores Sexuais , Taxa de Sobrevida , Taiwan/epidemiologia , TempoRESUMO
INTRODUCTION: Diabetes mellitus (DM) is a major risk of cardiovascular events. Bioresorbable stent frame materials capable of providing mechanical support and drug-delivery functions have been developed in an attempt to improve long-term outcomes. However, publications about the long-term outcomes of bioresorbable scaffolds (BRS) in DM patients are still limited. The aim of this study was to investigate the long-term safety and efficacy of BRS between patients with and without diabetes. METHODS: Data regarding BRS placement in consecutive patients receiving percutaneous coronary interventions were collected from the cardiovascular center of a single tertiary medical center from 2014 to 2017. RESULTS: A total of 138 cases were included and followed up for 4 years. The mortality rate was 1.1% in the non-diabetic group and 4.1% in the diabetic group (p = 0.2542). No cardiac mortality was observed. One patient had an acute myocardial infarction (0.7%) in the non-diabetic group. The rate of target lesion revascularization was 3.4% in the non-diabetic group and 4.08% in the diabetic group. The ratio of target vessel revascularization was 6.74% in the non-diabetic group and 4.1% in the diabetic group. CONCLUSIONS: This study demonstrated no significant difference in long-term outcomes after BRS implantation between patients with and without diabetes in a single tertiary medical center.
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Pulmonary arterial hypertension (PAH) is an incurable chronic and progressive debilitating disease associated with significant morbidity and mortality. The World Health Organization functional class (WHO FC) at diagnosis and at follow-up remains one of the strongest predictors of survival in PAH. Studies have shown improved long-term outcomes in PAH patients who received PAH-specific treatment, as monotherapy or as combination therapy, early in their disease course. Studies have also shown that without treatment, PAH rapidly deteriorates even in patients with less advanced (low risk) disease state. In this article, we review evidence from randomized controlled clinical trials to support our position on the importance of early PAH management in WHO FC II patients. The growing importance of combination therapy in the early treatment of PAH and recommendations by the most recent guidelines for the diagnosis and treatment of pulmonary hypertension are also discussed in this article.
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ß-Blockers are a standard therapy for acute myocardial infarction (AMI) due to their better short-term and long-term outcomes. However, ß-blockers are often under-prescribed in chronic obstructive pulmonary disease (COPD) patients with AMI, since they are thought be related to bronchospasm. The aim of this study was to investigate the association between the usage of ß-blockers and the risk of mortality in COPD patients after first AMI via a nationwide, population-based cohort study. In this retrospective study, we identified 186,326 patients with AMI diagnosed between January 2000 and December 2012, 23,116 of whom had COPD, from the National Health Insurance Research Database. A total of 7609 patients (32.92%) were prescribed ß-blockers, while 15,507 were not. The ß-blocker patients were stratified into selective and non-selective ß-blocker groups. Multivariate Cox proportional hazards models were used to estimate adjusted hazard ratios (HR) with 95% confidence intervals (95% CI). Selective ß-blocker use showed a reduced risk of mortality, as compared with patients without ß-blockers (HR 0.93; 95% CI 0.89-0.98; p < 0.01) while non-selective ß-blocker groups did not increase the risk of mortality compared to the patients without ß-blockers (HR 0.98; 95% CI 0.94-1.02; p = 0.38). In addition, the use of ß-blockers was found to be associated with a reduced risk of mortality in most stratified analyses which was seen particularly in males, patients aged 65 years and above, and in individuals with an array of comorbidities. These findings suggest that ß-blockers improve overall survival among COPD patients after first AMI.
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Antagonistas Adrenérgicos beta/uso terapêutico , Infarto do Miocárdio/diagnóstico , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Doença Aguda , Idoso , Idoso de 80 Anos ou mais , Bloqueadores dos Canais de Cálcio/uso terapêutico , Feminino , Hospitalização , Humanos , Masculino , Análise Multivariada , Infarto do Miocárdio/complicações , Infarto do Miocárdio/mortalidade , Modelos de Riscos Proporcionais , Doença Pulmonar Obstrutiva Crônica/complicações , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Estudos Retrospectivos , TaiwanRESUMO
Pulmonary arterial hypertension (PAH) is characterized as a progressive and sustained increase in pulmonary vascular resistance, which may induce right ventricular failure. In 2014, the Working Group on Pulmonary Hypertension of the Taiwan Society of Cardiology (TSOC) conducted a review of data and developed a guideline for the management of PAH.4 In recent years, several advancements in diagnosis and treatment of PAH has occurred. Therefore, the Working Group on Pulmonary Hypertension of TSOC decided to come up with a focused update that addresses clinically important advances in PAH diagnosis and treatment. This 2018 focused update deals with: (1) the role of echocardiography in PAH; (2) new diagnostic algorithm for the evaluation of PAH; (3) comprehensive prognostic evaluation and risk assessment; (4) treatment goals and follow-up strategy; (5) updated PAH targeted therapy; (6) combination therapy and goal-orientated therapy; (7) updated treatment for PAH associated with congenital heart disease; (8) updated treatment for PAH associated with connective tissue disease; and (9) updated treatment for chronic thromboembolic pulmonary hypertension.
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Guias de Prática Clínica como Assunto , Hipertensão Arterial Pulmonar/diagnóstico , Hipertensão Arterial Pulmonar/terapia , Cardiologia , Humanos , Sociedades Médicas , TaiwanRESUMO
Pulmonary arterial hypertension (PAH) is characterized by pulmonary arterial proliferation and remodeling, resulting in a specific increase in right ventricle systolic pressure (RVSP) and, ultimately right ventricular failure. Recent studies have demonstrated that caffeic acid phenethyl ester (CAPE) exerts a protective role in NF-κB-mediated inflammatory diseases. However, the effect of CAPE on PAH remains to be elucidated. In this study, monocrotaline (MCT) was used to establish PAH in rats. Two weeks after the induction of PAH by MCT, CAPE was administrated by intraperitoneal injection once a day for two weeks. Pulmonary hemodynamic measurements and pulmonary artery morphological assessments were examined. Our results showed that administration of CAPE significantly suppressed MCT-induced vascular remodeling by decreasing the HIF-1α expression and PDGF-BB production, and improved in vivo RV systolic performance in rats. Furthermore, CAPE inhibits hypoxia- and PDGF-BB-induced HIF-1α expression by decreasing the activation of the AKT/ERK pathway, which results in the inhibition of human pulmonary artery smooth muscle cells (hPASMCs) proliferation and prevention of cells resistant to apoptosis. Overall, our data suggest that HIF-1α is regarded as an alternative target for CAPE in addition to NF-κB, and may represent a promising therapeutic agent for the treatment of PAH diseases.
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Ácidos Cafeicos/farmacologia , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Hipertensão Pulmonar/etiologia , Hipertensão Pulmonar/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Álcool Feniletílico/análogos & derivados , Fator de Crescimento Derivado de Plaquetas/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Modelos Animais de Doenças , Expressão Gênica , Hemodinâmica/efeitos dos fármacos , Humanos , Hipertensão Pulmonar/diagnóstico , Hipertensão Pulmonar/tratamento farmacológico , Hipertrofia Ventricular Direita/tratamento farmacológico , Hipertrofia Ventricular Direita/etiologia , Hipertrofia Ventricular Direita/metabolismo , Hipertrofia Ventricular Direita/fisiopatologia , Imuno-Histoquímica , Álcool Feniletílico/farmacologia , Fator de Crescimento Derivado de Plaquetas/genética , Artéria Pulmonar/efeitos dos fármacos , Artéria Pulmonar/metabolismo , Artéria Pulmonar/fisiopatologia , Ratos , Transdução de Sinais/efeitos dos fármacos , Remodelação Vascular/efeitos dos fármacosRESUMO
Low shear stress has been proposed to play a reparative role in modulating cartilage homeostasis. Recently, epidemiological studies have found a positive correlation between the resistin level in serum and synovial fluid and osteoarthritis (OA) severity in patients. However, the effect of moderate shear stress on the catabolic stimulation of resistin in OA chondrocytes remains unclear. Hence, this study was to investigate whether low shear stress could regulate resistin-induced catabolic cyclooxygenase (COX)-2 expression in human OA chondrocytes and the underlying mechanism. Human OA chondrocytes and SW1353 chondrosarcoma cells were used in this study. Two modes of low shear stress (2 dyn/cm2 ), pre-shear and post-shear, were applied to the chondrocytes. A specific activator and siRNAs were used to investigate the mechanism of low shear stress-regulated COX-2 expression of resistin induction. We found that human OA chondrocytes exposed to different modes of low shear stress elicit an opposite effect on resistin-induced COX-2 expression: pre-shear for a short duration attenuates the resistin effect by inhibiting the transcription factor nuclear factor (NF)-κB-p65 subunit and the cAMP response element binding protein; however, post-shear over a longer duration enhances the resistin effect by activating only the NF-κB-p65 subunit. Moreover, our results demonstrated that the regulation of both shear modes in resistin-stimulated COX-2 expression occurs through increasing AMP-activated protein kinase activation and then sirtuin 1 expression. This study elucidates the detailed mechanism of low shear stress regulating the resistin-induced catabolic COX-2 expression and indicates a possible reparative role of moderate shear force in resistin-stimulated OA development. J. Cell. Physiol. 232: 1448-1457, 2017. © 2016 Wiley Periodicals, Inc.
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Condrócitos/enzimologia , Ciclo-Oxigenase 2/genética , Osteoartrite/enzimologia , Osteoartrite/patologia , Resistina/farmacologia , Estresse Mecânico , Proteínas Quinases Ativadas por AMP/metabolismo , Idoso , Linhagem Celular Tumoral , Condrócitos/efeitos dos fármacos , Condrócitos/patologia , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Ciclo-Oxigenase 2/metabolismo , Humanos , Pessoa de Meia-Idade , Modelos Biológicos , NF-kappa B/metabolismo , Osteoartrite/genética , Regiões Promotoras Genéticas/genética , Transdução de Sinais/efeitos dos fármacos , Sirtuína 1/metabolismoRESUMO
Osteoarthritis (OA) is currently still an irreversible degenerative disease of the articular cartilage. Recent, dextrose (d-glucose) intraarticular injection prolotherapy for OA patients has been reported to benefit the chondrogenic stimulation of damaged cartilage. However, the detailed mechanism of glucose's effect on cartilage repair remains unclear. Chitosan, a naturally derived polysaccharide, has recently been investigated as a surgical or dental dressing to control breeding. Therefore, in this study, glucose was adsorbed to chitosan membranes (CTS-Glc), and the study aimed to investigate whether CTS-Glc complex membranes could regulate the proliferation of human OA chondrocytes and to explore the underlying mechanism. Human OA and SW1353 chondrocytes were used in this study. The experiments involving the transfection of cells used SW1353 chondrocytes. A specific inhibitor and siRNAs were used to investigate the mechanism underlying the CTS-Glc-regulated proliferation of human chondrocytes. We found that CTS-Glc significantly increased the proliferation of both human OA and SW1353 chondrocytes comparable to glucose- or chitosan-only stimulation. The role of mammalian target of rapamycin complex 1 (mTORC1) signaling, including mTOR, raptor, and S6k proteins, has been demonstrated in the regulation of CTS-Glc-increased human chondrocyte proliferation. mTORC1 signaling increased the expression levels of maturated SREBP-1 and FASN and then induced the expressions of cell cycle regulators, that is, cyclin D, cyclin-dependent kinase-4 and -6 in human chondrocytes. This study elucidates the detailed mechanism behind the effect of CTS-Glc complex membranes in promoting chondrocyte proliferation and proposes a possible clinical application of the CTS-Glc complex in the dextrose intraarticular injection of OA prolotherapy in the future to attenuate the pain and discomfort of OA patients.
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Antirreumáticos/farmacologia , Proliferação de Células/efeitos dos fármacos , Quitosana/farmacologia , Condrócitos/efeitos dos fármacos , Glucose/farmacologia , Membranas Artificiais , Complexos Multiproteicos/metabolismo , Osteoartrite/tratamento farmacológico , Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Adsorção , Idoso , Antirreumáticos/química , Técnicas de Cultura de Células , Linhagem Celular , Quitosana/química , Condrócitos/enzimologia , Ciclina D1/metabolismo , Quinase 4 Dependente de Ciclina/metabolismo , Quinase 6 Dependente de Ciclina/metabolismo , Ácido Graxo Sintase Tipo I/metabolismo , Feminino , Glucose/química , Humanos , Masculino , Alvo Mecanístico do Complexo 1 de Rapamicina , Pessoa de Meia-Idade , Complexos Multiproteicos/antagonistas & inibidores , Complexos Multiproteicos/genética , Osteoartrite/enzimologia , Inibidores de Proteínas Quinases/farmacologia , Interferência de RNA , Proteína Regulatória Associada a mTOR , Transdução de Sinais/efeitos dos fármacos , Serina-Treonina Quinases TOR/antagonistas & inibidores , Serina-Treonina Quinases TOR/genética , Fatores de Tempo , Transfecção , Homólogo LST8 da Proteína Associada a mTORRESUMO
BACKGROUND: Previous studies regarding the cardioprotective effects of dipeptidyl peptidase 4 (DPP-4) inhibitors have not provided sufficient evidence of a relationship between DPP-4 inhibition and actual cardiovascular outcomes. This study aimed to evaluate the impact of DPP-4 inhibitors on the survival of diabetic patients after first acute myocardial infarction (AMI). METHODS: This was a nationwide, propensity score-matched, case-control study of 186,112 first AMI patients, 72,924 of whom had diabetes. A propensity score, one-to-one matching technique was used to match 2672 controls to 2672 patients in the DPP-4 inhibitor group for analysis. Controls were matched based on gender, age, and a history of hypertension, dyslipidemia, diabetes, peripheral vascular disease, heart failure, cerebrovascular accident, end-stage renal disease, chronic obstructive pulmonary disease, and percutaneous coronary intervention. RESULTS: DPP-4 inhibitors improve the overall 3-year survival rate (log rank P < 0.0001), whether male or female. Cox proportional hazard regression showed DPP-4 inhibitor is beneficial in diabetes patients after AMI (HR = 0.86; 95% CI 0.78-0.95), especially in those patients with hypertension (HR = 0.87; 95% CI 0.78-0.97; P = 0.0103) and cerebrovascular disease (HR = 0.83; 95% CI 0.72-0.97; P = 0.018), but without dyslipidemia (HR = 0.78; 95% CI 0.67-0.92; P = 0.0029), without peripheral vascular disease (HR = 0.86; 95% CI 0.78-0.96; P = 0.0047), without heart failure (HR = 0.84; 95% CI 0.73-0.96; P = 0.0106), without end stage renal disease (HR = 0.86; 95% CI 0.77-0.95; P = 0.0035), and without chronic obstructive pulmonary disease (HR = 0.87; 95% CI 0.78-0.97; P = 0.0096). CONCLUSIONS: DPP-4 inhibitor therapy improved long-term survival in diabetic patients after first AMI, regardless of gender.
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Diabetes Mellitus Tipo 2/mortalidade , Inibidores da Dipeptidil Peptidase IV/uso terapêutico , Falência Renal Crônica/tratamento farmacológico , Infarto do Miocárdio/mortalidade , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Feminino , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/mortalidade , Humanos , Hipoglicemiantes/uso terapêutico , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/complicações , Infarto do Miocárdio/tratamento farmacológico , Intervenção Coronária Percutânea/métodos , TempoRESUMO
BACKGROUND: To the best of our knowledge, no study has compared gram-negative bacillary hematogenous pyogenic spondylodiscitis (GNB-HPS) with gram-positive coccal hematogenous pyogenic spondylodiscitis (GPC-HPS) regarding their clinical characteristics and outcomes. METHODS: From January 2003 to January 2013, 54 patients who underwent combined antibiotic and surgical therapy in the treatment of hematogenous pyogenic spondylodiscitis were included. RESULTS: Compared with 37 GPC-HPS patients, the 17 GNB-HPS patients were more often found to be older individuals, a history of cancer, and a previous history of symptomatic urinary tract infection. They also had a less incidence of epidural abscess formation compared with GPC-HPS patients from findings on magnetic resonance imaging (MRI). Constitutional symptoms were the primary reasons for initial physician visits in GNB-HPS patients whereas pain in the affected spinal region was the most common manifestation in GPC-HPS patients at initial visit. The clinical outcomes of GNB-HPS patients under combined surgical and antibiotic treatment were not different from those of GPC-HPS patients. In multivariate analysis, independent predicting risk factors for GNB-HPS included a malignant history and constitutional symptoms and that for GPC-HPS was epidural abscess. CONCLUSIONS: The clinical manifestations and MRI presentations of GNB-HPS were distinguishable from those of GPC-HPS.
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Antibacterianos/uso terapêutico , Discite/microbiologia , Discite/terapia , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Infecções por Bactérias Gram-Positivas/tratamento farmacológico , Adulto , Idoso , Discite/diagnóstico por imagem , Feminino , Infecções por Bactérias Gram-Negativas/diagnóstico por imagem , Infecções por Bactérias Gram-Negativas/etiologia , Infecções por Bactérias Gram-Negativas/cirurgia , Infecções por Bactérias Gram-Positivas/diagnóstico por imagem , Infecções por Bactérias Gram-Positivas/etiologia , Infecções por Bactérias Gram-Positivas/cirurgia , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Resultado do TratamentoRESUMO
BACKGROUND: Prolonged bisphosphonate treatment might suppress bone remodeling to the extent that normal bone repair is impaired. While this adverse side effect is usually ascribed to the negative effects of bisphosphonates on osteoclast survival and function, these effects on osteoblasts are still unclear. METHODS: In the current study, we hypothesized that zoledronate (ZOL) at the µM level might present negative effects on osteoblast survival and function. In vitro analyses of proliferation, migration and differentiation were performed on human osteoblast-like cells. RESULTS: Our results revealed that ZOL treatment dose- and time-dependently induced apoptosis of osteoblasts after concentrations had reached 10 µM (p < 0.001). The concentrations at which ZOL inhibited osteoblast migration by 50 % were between 10 and 15 µM. Moreover, there was a dose-dependent reduction in the extent of matrix mineralization, but without a concomitant inhibition of osteogenic differentiation in terms of secreted type I collagen and osteocalcin and of alkaline phosphatase activity per viable cell. Analyses of the expression of osteogenic genes confirmed that ZOL at the µM level had no effects on osteogenic differentiation of osteoblasts. CONCLUSION: We concluded that ZOL at the µM level affected osteoblast survival and migration, but did not affect differentiation. The pathophysiological implications of ZOL at the µM level on skeletal disorders need to be investigated and clarified in the future researches.
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Conservadores da Densidade Óssea/farmacologia , Proliferação de Células/efeitos dos fármacos , Difosfonatos/farmacologia , Imidazóis/farmacologia , Osteoblastos/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Diferenciação Celular/fisiologia , Linhagem Celular , Proliferação de Células/fisiologia , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Células Cultivadas , Relação Dose-Resposta a Droga , Humanos , Osteoblastos/fisiologia , Ácido ZoledrônicoRESUMO
UNLABELLED: Pulmonary hypertension (PH) is a hemodynamic and pathophysiologic condition, defined as a mean pulmonary arterial pressure exceeding 25 mmHg at rest. According to the recent classifications, it is grouped into pulmonary arterial hypertension (PAH), heart-related, lung-related, thromboembolic, and miscellaneous PH. In the past two decades, tremendous advances have occurred in the field of PH. These include (1) development of clinical diagnostic algorithm and a monitoring strategy dedicated to PAH, (2) defining strong rationales for screening at-risk populations, (3) advent of pulmonary specific drugs which makes PAH manageable, (4) recognition of needs of having proper strategy of combining existing pulmonary specific drugs, and/or potential novel drugs, (5) pursuit of clinical trials with optimal surrogate endpoints and study durations, (6) recognition of critical roles of PH/right ventricular function, as well as interdependence of ventricles in different conditions, especially those with various phenotypes of heart failure, and (7) for rare diseases, putting equal importance on carefully designed observation studies, various registries, etc., besides double blind randomized studies. In addition, ongoing basic and clinical research has led to further understanding of relevant physiology, pathophysiology, epidemiology and genetics of PH/PAH. This guidelines from the working group of Pulmonary Hypertension of the Taiwan Society of Cardiology is to provide updated guidelines based on the most recent international guidelines as well as Taiwan's domestic research on PH. The guidelines are mainly for the management of PAH (Group 1) ; however the majority of content can be helpful for managing other types of PH. KEY WORDS: Pulmonary arterial hypertension; Taiwan guidelines.
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AIMS: Pulmonary arterial hypertension (PAH) is characterized by extensive pulmonary arterial remodelling. Although mesenchymal stem cell (MSC)-derived exosomes provide protective effects in PAH, MSCs exhibit limited senescence during in vitro expansion compared with the induced pluripotent stem cells (iPSCs). Moreover, the exact mechanism is not known. METHODS AND RESULTS: In this study, we used murine iPSCs generated from mouse embryonic fibroblasts with triple factor (Oct4, Klf4, and Sox2) transduction to determine the efficacy and action mechanism of iPSC-derived exosomes (iPSC-Exo) in attenuating PAH in rats with monocrotaline (MCT)-induced pulmonary hypertension. Both early and late iPSC-Exo treatment effectively prevented the wall thickening and muscularization of pulmonary arterioles, improved the right ventricular systolic pressure, and alleviated the right ventricular hypertrophy in MCT-induced PAH rats. Pulmonary artery smooth muscle cells (PASMC) derived from MCT-treated rats (MCT-PASMC) developed more proliferative and pro-migratory phenotypes, which were attenuated by the iPSC-Exo treatment. Moreover, the proliferation and migration of MCT-PASMC were reduced by iPSC-Exo with suppression of PCNA, cyclin D1, MMP-1, and MMP-10, which are mediated via the HIF-1α and P21-activated kinase 1/AKT/Runx2 pathways. CONCLUSION: IPSC-Exo are effective at reversing pulmonary hypertension by reducing pulmonary vascular remodelling and may provide an iPSC-free therapy for the treatment of PAH.
Assuntos
Exossomos , Hipertensão Pulmonar , Células-Tronco Pluripotentes Induzidas , Hipertensão Arterial Pulmonar , Ratos , Animais , Camundongos , Hipertensão Arterial Pulmonar/metabolismo , Células-Tronco Pluripotentes Induzidas/metabolismo , Remodelação Vascular , Exossomos/metabolismo , Fibroblastos/metabolismo , Hipertensão Pulmonar Primária Familiar/metabolismo , Artéria Pulmonar , Monocrotalina/efeitos adversos , Monocrotalina/metabolismo , Proliferação de Células , Modelos Animais de Doenças , Subunidade alfa 1 de Fator de Ligação ao Core/metabolismoRESUMO
In Riociguat rEplacing PDE5i therapy evaLuated Against Continued PDE5i thErapy (REPLACE) (NCT02891850), improvements in risk status were observed in patients with pulmonary arterial hypertension (PAH) at intermediate risk switching to riociguat versus continuing phosphodiesterase-5 inhibitors (PDE5i). This post hoc study applied the Registry to Evaluate Early and Long-Term PAH Disease Management (REVEAL) Lite 2 and Comparative Prospective Registry of Newly Initiated Therapies for Pulmonary (COMPERA) 2.0 risk-assessment tools to REPLACE to investigate the impact of baseline risk status on clinical improvement. The proportions of riociguat- and PDE5i-treated patients achieving the primary end-point at REVEAL Lite 2 low, intermediate, and high baseline risk reflected the overall population. Proportions of riociguat-treated patients achieving the primary end-point were comparable between the COMPERA 2.0 intermediate-low risk (39%) and intermediate-high risk (43%) groups. Our findings show that patients in REPLACE achieved clinical improvement by switching from PDE5i to riociguat across all COMPERA 2.0 and most REVEAL Lite 2 baseline risk strata.
RESUMO
BACKGROUND: The long-term outcome on patients with chronic thromboembolic pulmonary hypertension (CTEPH) has not been ideal after standard medical treatment. However, good outcome for patients with CTEPH after interventions such as pulmonary endarterectomy (PEA) and balloon pulmonary angioplasty (BPA) has been reported recently. The aim of this study was to evaluate the impact of PEA or BPA on long-term outcomes for CTEPH patients in Han-Chinese population. METHODS: This was a multicenter, prospective case-control study. Patients with CTEPH were enrolled between January, 2018 and March, 2020. They were divided into two groups, including intervention (PEA or BPA) and conservative groups. The followed-up period was 26 months after treatment. The endpoints were all-cause mortality and CTEPH mortality. RESULTS: A total of 129 patients were enrolled and assigned to receive PEA/BPA (N = 73), or conservative therapy (N = 56). Overall, the 26-month survival rate of all-cause mortality was significantly higher in intervention group compared to that in conservative group (95.89% vs 80.36%; log-rank p = 0.0164). The similar trend was observed in the 26-month survival rate of CTEPH mortality (97.26% vs 85.71%; log-rank p = 0.0355). Regarding Cox proportional-hazard regression analysis, the hazard ratios (HRs) on patients with CTEPH receiving intervention in the outcome of all-cause mortality and CTEPH mortality were statistically significant (HR = 0.07 and p = 0.0141 in all-cause mortality; HR = 0.11 and p = 0.0461 in CTEPH mortality). CONCLUSION: This multicenter prospective case-control study demonstrated that intervention such as PEA and BPA increased the long-term survival rate for patient with CTEPH significantly. Intervention was an independent factor in long-term outcome for patients with CTEPH, including all-cause mortality and CTEPH mortality.