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1.
Acta Cardiol Sin ; 40(1): 97-110, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38264068

RESUMO

Background: The door-to-balloon (D2B) time is a critical quality measure in managing ST-segment elevation myocardial infarction (STEMI) patients receiving primary percutaneous coronary intervention (PCI). We developed an integrated STEMI activation system, named Acute Myocardial Infarction Software Aids (AMISTAD), to optimize care for STEMI patients. This study aimed to evaluate the impact of the AMISTAD system on D2B times and clinical outcomes. Methods: We retrospectively collected data of consecutive STEMI patients receiving primary PCI between July 2017 and December 2018 at a single center. The patients were categorized into AMISTAD and non-AMISTAD groups. Outcomes included D2B time, length of hospital stay, and 12-month cardiovascular outcomes. Data were analyzed using multiple regression models; subgroup and sensitivity analyses were applied to examine the robustness of the results. Results: A total of 114 STEMI patients were enrolled (38 AMISTAD, 76 non-AMISTAD). The AMISTAD group had a significantly shorter mean D2B time (66.7 ± 13.2 vs. 76.6 ± 24.9 minutes, p = 0.02) and non-significantly shorter length of hospital stay (4.7 vs. 7.2 days, p = 0.09). The 12-month cardiovascular outcomes between the two groups were not significantly different (adjusted hazard ratio 0.79, 95% confidence interval 0.30-2.09, p = 0.64). Subgroup and sensitivity analyses had consistent outcomes. Conclusions: Integrating the AMISTAD system into the STEMI workflow was associated with a reduced D2B time and shorter hospital stay. Further research involving larger cohorts and extended follow-up periods is needed to assess the generalizability and impact on cardiovascular outcomes. The AMISTAD system has the potential to improve the quality of care for STEMI patients.

2.
Cardiovasc Diabetol ; 22(1): 82, 2023 04 07.
Artigo em Inglês | MEDLINE | ID: mdl-37029406

RESUMO

BACKGROUND: A new definition of metabolically healthy obesity (MHO) has recently been proposed to stratify the heterogeneous mortality risk of obesity. Metabolomic profiling provides clues to metabolic alterations beyond clinical definition. We aimed to evaluate the association between MHO and cardiovascular events and assess its metabolomic pattern. METHODS: This prospective study included Europeans from two population-based studies, the FLEMENGHO and the Hortega study. A total of 2339 participants with follow-up were analyzed, including 2218 with metabolomic profiling. Metabolic health was developed from the third National Health and Nutrition Examination Survey and the UK biobank cohorts and defined as systolic blood pressure < 130 mmHg, no antihypertensive drugs, waist-to-hip ratio < 0.95 for women or 1.03 for men, and the absence of diabetes. BMI categories included normal weight, overweight, and obesity (BMI < 25, 25-30, ≥ 30 kg/m2). Participants were classified into six subgroups according to BMI category and metabolic healthy status. Outcomes were fatal and nonfatal composited cardiovascular events. RESULTS: Of 2339 participants, the mean age was 51 years, 1161 (49.6%) were women, 434 (18.6%) had obesity, 117 (5.0%) were classified as MHO, and both cohorts had similar characteristics. Over a median of 9.2-year (3.7-13.0) follow-up, 245 cardiovascular events occurred. Compared to those with metabolically healthy normal weight, individuals with metabolic unhealthy status had a higher risk of cardiovascular events, regardless of BMI category (adjusted HR: 3.30 [95% CI: 1.73-6.28] for normal weight, 2.50 [95% CI: 1.34-4.66] for overweight, and 3.42 [95% CI: 1.81-6.44] for obesity), whereas those with MHO were not at increased risk of cardiovascular events (HR: 1.11 [95% CI: 0.36-3.45]). Factor analysis identified a metabolomic factor mainly associated with glucose regulation, which was associated with cardiovascular events (HR: 1.22 [95% CI: 1.10-1.36]). Individuals with MHO tended to present a higher metabolomic factor score than those with metabolically healthy normal weight (0.175 vs. -0.057, P = 0.019), and the score was comparable to metabolically unhealthy obesity (0.175 vs. -0.080, P = 0.91). CONCLUSIONS: Individuals with MHO may not present higher short-term cardiovascular risk but tend to have a metabolomic pattern associated with higher cardiovascular risk, emphasizing a need for early intervention.


Assuntos
Doenças Cardiovasculares , Obesidade Metabolicamente Benigna , Masculino , Humanos , Feminino , Pessoa de Meia-Idade , Obesidade Metabolicamente Benigna/diagnóstico , Obesidade Metabolicamente Benigna/epidemiologia , Sobrepeso , Fatores de Risco , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/prevenção & controle , Estudos Prospectivos , Inquéritos Nutricionais , Índice de Massa Corporal , Obesidade/diagnóstico , Obesidade/epidemiologia , Fatores de Risco de Doenças Cardíacas , Fenótipo
3.
Immunity ; 40(1): 40-50, 2014 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-24412616

RESUMO

Fibrosis in response to tissue damage or persistent inflammation is a pathological hallmark of many chronic degenerative diseases. By using a model of acute peritoneal inflammation, we have examined how repeated inflammatory activation promotes fibrotic tissue injury. In this context, fibrosis was strictly dependent on interleukin-6 (IL-6). Repeat inflammation induced IL-6-mediated T helper 1 (Th1) cell effector commitment and the emergence of STAT1 (signal transducer and activator of transcription-1) activity within the peritoneal membrane. Fibrosis was not observed in mice lacking interferon-γ (IFN-γ), STAT1, or RAG-1. Here, IFN-γ and STAT1 signaling disrupted the turnover of extracellular matrix by metalloproteases. Whereas IL-6-deficient mice resisted fibrosis, transfer of polarized Th1 cells or inhibition of MMP activity reversed this outcome. Thus, IL-6 causes compromised tissue repair by shifting acute inflammation into a more chronic profibrotic state through induction of Th1 cell responses as a consequence of recurrent inflammation.


Assuntos
Interleucina-6/metabolismo , Peritônio/patologia , Peritonite/genética , Peritonite/patologia , Células Th1/imunologia , Doença Aguda , Transferência Adotiva , Animais , Células Cultivadas , Doença Crônica , Modelos Animais de Doenças , Matriz Extracelular/imunologia , Retroalimentação Fisiológica , Fibrose , Humanos , Interferon gama/genética , Interferon gama/metabolismo , Interleucina-6/genética , Interleucina-6/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Fator de Transcrição STAT1/genética , Fator de Transcrição STAT1/metabolismo , Transdução de Sinais , Células Th1/transplante
4.
Nephrology (Carlton) ; 28(11): 581-587, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37549919

RESUMO

The world healthcare system is actively seeking possible solutions for the rapid growth of kidney disease threats. The Taiwan Renal Data System (TWRDS) was central in assisting kidney health and care policymaking to reduce end-stage kidney disease incidence and mortality. This article summarizes the TWRDS framework, recent applications, and developments to provide new insights for some international researchers to promote planetary kidney health. The TWRDS originated in 1987 for the accreditation and quality monitoring of dialysis units and was connected with enriched health claim databases after the implementation of universal national health insurance in Taiwan in 1995. As a healthcare information centre, TWRDS has published annual reports forming indispensable instructions for renal care improvement since 2014. The TWRDS possesses three main functions: (1) kidney disease surveillance; (2) offering rich materials for research purposes; (3) achieving precision prevention and care through complex algorithms. In the new era, TWRDS can help build a more resilient society against communicable disease threats by integrating remote sensor techniques for developing future remote healthcare structures, as well as identifying kidney health inequity populations and promoting healthcare resources distributed equity. The global healthcare system is facing escalating burdens of non-communicable disease care due to the rapidly growing elderly population. Therefore, a considerable-scale data system is an essential decision-supportive tool in promoting an evidence-based, resilient, sustainable, equity care environment. Undoubtedly, TWRDS experience is a practical example of leveraging healthcare providers' decisions, care outcomes, and renovation.


Assuntos
Falência Renal Crônica , Diálise Renal , Idoso , Humanos , Taiwan/epidemiologia , Atenção à Saúde , Falência Renal Crônica/diagnóstico , Falência Renal Crônica/epidemiologia , Falência Renal Crônica/terapia , Rim
5.
Acta Cardiol Sin ; 39(6): 783-806, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-38022422

RESUMO

Cardiac rehabilitation is a comprehensive intervention recommended in international and Taiwanese guidelines for patients with acute myocardial infarction. Evidence supports that cardiac rehabilitation improves the health-related quality of life, enhances exercise capacity, reduces readmission rates, and promotes survival in patients with cardiovascular disease. The cardiac rehabilitation team is comprehensive and multidisciplinary. The inpatient, outpatient, and maintenance phases are included in cardiac rehabilitation. All patients admitted with acute myocardial infarction should be referred to the rehabilitation department as soon as clinically feasible. Pre-exercise evaluation, including exercise testing, helps physicians identify the risks of cardiac rehabilitation and organize appropriate exercise prescriptions. Therefore, the Taiwan Myocardial Infarction Society (TAMIS), Taiwan Society of Cardiology (TSOC), and Taiwan Academy of Cardiovascular and Pulmonary Rehabilitation (TACVPR) address this consensus statement to assist healthcare practitioners in performing cardiac rehabilitation in patients with acute myocardial infarction.

6.
J Cell Mol Med ; 26(10): 2972-2980, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35415928

RESUMO

The purpose of this phase I clinical trial is to assess the safety and tolerability of allogeneic adipose tissue-derived stem cells (ADSCs) among chronic kidney disease (CKD) patients. 12 eligible CKD patients with an estimated glomerular filtration rate (eGFR) of 15-44 ml/min/1.73 m2 received one dose of intravenous allogeneic ADSCs (ELIXCYTE® ), as 3 groups: 3 low dose (6.4 × 107 cells in total of 8 ml), 3 middle dose (19.2 × 107 cells in total of 24 ml) and 6 high dose (32.0 × 107 cells in total of 40 ml) of ELIXCYTE® and evaluated after 48 weeks. Primary endpoint was the safety profiles in terms of incidence of adverse events (AEs) and serious adverse event (SAE). Two subjects in high dose group experienced a total of 2 treatment-related AEs which are Grade 1 slow speech and Grade 1 bradyphrenia after the infusion. One subject in middle dose group experienced an SAE unlikely related to treatment, grade 2 proteinuria. No fatal AE was reported in this study. An increase in eGFR was observed in 7 out of 12 subjects (58%) at Week 24 and in 6 of 12 subjects (50%) by Week 48. By Week 24, an increase in eGFR by more than 20% among all CKD patients with baseline eGFR â‰§ 30 ml/min/1.73 m2 as compared to only 2 subjects in baseline eGFR < 30 ml/min/1.73 m2  group. No significant reduction in proteinuria was noted among all subjects. This phase I trial demonstrated single-dose intravenous ELIXCYTE was well tolerated in moderate-to-severe CKD patients and its preliminary efficacy warrants future studies.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Insuficiência Renal Crônica , Tecido Adiposo , Estudos de Viabilidade , Feminino , Humanos , Masculino , Insuficiência Renal Crônica/tratamento farmacológico , Resultado do Tratamento
7.
HIV Med ; 23(2): 111-120, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34494350

RESUMO

As the life expectancy of people living with HIV (PLWH) approaches that of the general population, the burden of comorbidities such as cardiovascular disease (CVD) is increasing. Regardless of HIV status, about 50% of CVD deaths worldwide occur in Asia, and Asian PLWH have a high prevalence of conventional CVD risk factors, such as smoking, dyslipidaemia, hypertension and insulin resistance or diabetes. As well as conventional CVD risk factors, PLWH have HIV-specific risk factors such as chronic inflammation, immune activation and endothelial damage, as well as risk factors related to antiretroviral therapy. This review describes the current knowledge on the epidemiology and risk factors of CVD in Asian PLWH and provides an Asian perspective on the recommendations for managing CVD risk in PLWH.


Assuntos
Doenças Cardiovasculares , Infecções por HIV , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Fatores de Risco de Doenças Cardíacas , Humanos , Expectativa de Vida , Fatores de Risco
8.
Arch Toxicol ; 96(10): 2731-2737, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35876889

RESUMO

Although anti-cancer therapy-induced cardiotoxicity is known, until now it lacks a reliable risk predictive model of the subsequent cardiotoxicity in breast cancer patients receiving anthracycline therapy. An artificial intelligence (AI) with a machine learning approach has yet to be applied in cardio-oncology. Herein, we aimed to establish a predictive model for differentiating patients at a high risk of developing cardiotoxicity, including cancer therapy-related cardiac dysfunction (CTRCD) and symptomatic heart failure with reduced ejection fraction. This prospective single-center study enrolled patients with newly diagnosed breast cancer who were preparing for anthracycline therapy from 2014 to 2018. We randomized the patients into a 70%/30% split group for ML model training and testing. We used 15 variables, including clinical, chemotherapy, and echocardiographic parameters, to construct a random forest model to predict CTRCD and heart failure with a reduced ejection fraction (HFrEF) during the 3-year follow-up period (median, 30 months). Comparisons of the predictive accuracies among the random forest, logistic regression, support-vector clustering (SVC), LightGBM, K-nearest neighbor (KNN), and multilayer perceptron (MLP) models were also performed. Notably, predicting CTRCD using the MLP model showed the best accuracy compared with the logistic regression, random forest, SVC, LightGBM, and KNN models. The areas under the curves (AUC) of MLP achieved 0.66 with the sensitivity and specificity as 0.86 and 0.53, respectively. Notably, among the features, the use of trastuzumab, hypertension, and anthracycline dose were the major determinants for the development of CTRCD in the logistic regression. Similarly, MLP, logistic regression, and SVM also showed higher AUCs for predicting the development of HFrEF. We also validated the AI prediction model with an additional set of patients developing HFrEF, and MLP presented an AUC of 0.81. Collectively, an AI prediction model is promising for facilitating physicians to predict CTRCD and HFrEF in breast cancer patients receiving anthracycline therapy. Further studies are warranted to evaluate its impact in clinical practice.


Assuntos
Neoplasias da Mama , Cardiopatias , Insuficiência Cardíaca , Antraciclinas/toxicidade , Antibióticos Antineoplásicos/toxicidade , Inteligência Artificial , Neoplasias da Mama/induzido quimicamente , Neoplasias da Mama/tratamento farmacológico , Cardiotoxicidade , Feminino , Cardiopatias/induzido quimicamente , Insuficiência Cardíaca/induzido quimicamente , Insuficiência Cardíaca/tratamento farmacológico , Humanos , Estudos Prospectivos , Volume Sistólico
9.
J Am Soc Nephrol ; 32(10): 2501-2516, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34155061

RESUMO

BACKGROUND: Proximal tubular cells (PTCs) are the most abundant cell type in the kidney. PTCs are central to normal kidney function and to regeneration versus organ fibrosis following injury. This study used single-nucleus RNA sequencing (snRNAseq) to describe the phenotype of PTCs in renal fibrosis. METHODS: Kidneys were harvested from naïve mice and from mice with renal fibrosis induced by chronic aristolochic acid administration. Nuclei were isolated using Nuclei EZ Lysis buffer. Libraries were prepared on the 10× platform, and snRNAseq was completed using the Illumina NextSeq 550 System. Genome mapping was carried out with high-performance computing. RESULTS: A total of 23,885 nuclei were analyzed. PTCs were found in five abundant clusters, mapping to S1, S1-S2, S2, S2-cortical S3, and medullary S3 segments. Additional cell clusters ("new PTC clusters") were at low abundance in normal kidney and in increased number in kidneys undergoing regeneration/fibrosis following injury. These clusters exhibited clear molecular phenotypes, permitting labeling as proliferating, New-PT1, New-PT2, and (present only following injury) New-PT3. Each cluster exhibited a unique gene expression signature, including multiple genes previously associated with renal injury response and fibrosis progression. Comprehensive pathway analyses revealed metabolic reprogramming, enrichment of cellular communication and cell motility, and various immune activations in new PTC clusters. In ligand-receptor analysis, new PTC clusters promoted fibrotic signaling to fibroblasts and inflammatory activation to macrophages. CONCLUSIONS: These data identify unrecognized PTC phenotype heterogeneity and reveal novel PTCs associated with kidney fibrosis.


Assuntos
Células Epiteliais/metabolismo , Células Epiteliais/patologia , Túbulos Renais Proximais/patologia , Fenótipo , RNA/metabolismo , Transcriptoma , Animais , Ácidos Aristolóquicos , Comunicação Celular , Movimento Celular , Núcleo Celular , Mapeamento Cromossômico , Células Epiteliais/fisiologia , Fibroblastos/metabolismo , Fibrose , Macrófagos/metabolismo , Masculino , Camundongos , RNA/genética , Regeneração , Análise de Sequência de RNA
10.
J Formos Med Assoc ; 121(1 Pt 2): 258-268, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33840545

RESUMO

BACKGROUND/PURPOSE: The present study was designed to evaluate the local cardiology infrastructure and services for heart failure (HF) care in Taiwan hospitals and to compare the HF care with the hospitals in European countries. METHODS: Available data from a total of 98 medical centers and regional hospitals in Taiwan were analyzed. Each facility was given a single copy of the questionnaire between September and December 2019, and service records were extracted from the National Health Insurance Database. European data were adopted from the 2017 European Society of Cardiology Atlas. RESULTS: The number of cardiologists per million populations in Taiwan was 57.4, and it was lower than the European median (72.8). The median percentages of interventional and electrophysiologists among cardiologists were 64% and 15% in Taiwan, which were both higher than the European median values (12% and 5%, respectively). The accessibility rates to implantable cardioverter-defibrillator (ICD) and cardiac resynchronization therapy (CRT) in Taiwan were both higher (3.4 and 3.0 centers per million populations) comparing to those in European countries (median 1.6 and 1.5 centers per million populations). Comparing to 67 hospitals without HF care teams in Taiwan, 31 hospitals (31.6%) with HF teams have significantly more cardiology staff, enhanced procedural capabilities with more alternatives on oral or intravenous HF relevant medications. CONCLUSION: Our analysis clearly demonstrated discrepancies in cardiology subspecialties and CRT/ICD accessibilities between European countries and Taiwan. Variations in HF-focused services and facilities plus HF-directed medications have demonstrated significant differences among Taiwanese hospitals with or without HF care team.


Assuntos
Cardiologia , Insuficiência Cardíaca , Atenção à Saúde , Europa (Continente) , Insuficiência Cardíaca/terapia , Humanos , Taiwan
11.
J Formos Med Assoc ; 121 Suppl 1: S56-S63, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35090801

RESUMO

BACKGROUND: Despite having a well-established pre-end-stage kidney disease (pre-ESKD) care program, Taiwan has a high incidence of ESKD. Unrecovered incident dialysis may lead to the maintenance of dialysis. Contrast medium (CM) or general anesthesia (GA) may also induce dialysis. We aimed to examine the trends for incident dialysis, use of CM or GA, and its long-term trajectory outcomes. METHODS: Patients who received at least one dialysis intervention between 2010 and 2017 were identified using the National Health Insurance Research Database. We collected information on age, sex, comorbidities, causes of dialysis in outpatient or inpatient settings, use of CM or GA or pre-ESKD program enrolment before incident dialysis, and trajectory outcomes. RESULTS: Incident dialysis occurred more frequently in elderly inpatients with infectious diseases or previous chronic kidney disease (CKD). The number of patients who had a pre-ESKD care plan before incident dialysis increased from 25% in 2010 to 41% in 2017 (P < 0.001). In general, CM or GA exposure related with a higher mortality rate. Over the five-year longitudinal follow-up, patients without a history of CKD had a higher mortality rate than those with a history of CKD. CONCLUSION: Enrolment in the pre-ESKD care program increased, and inpatient incident dialysis decreased. The long-term survival of patients with CKD was higher than that of non-CKD patients after incident dialysis. CM or GA exposure appears to be related to dialysis-induced mortality, and further investigations are warranted.


Assuntos
Falência Renal Crônica , Insuficiência Renal Crônica , Idoso , Humanos , Incidência , Falência Renal Crônica/epidemiologia , Falência Renal Crônica/terapia , Diálise Renal , Insuficiência Renal Crônica/epidemiologia , Taiwan/epidemiologia
12.
PLoS Pathog ; 15(6): e1007850, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31242262

RESUMO

Invasive candidiasis, mainly caused by Candida albicans, is a serious healthcare problem with high mortality rates, particularly in immunocompromised patients. Innate immune cells express pathogen recognition receptors (PRRs) including C-type lectin-like receptors (CLRs) that bind C. albicans to initiate an immune response. Multiple CLRs including Dectin-1, Dectin-2 and Mincle have been proposed individually to contribute to the immune response to C. albicans. However how these receptors collaborate to clear a fungal infection is unknown. Herein, we used novel multi-CLR knockout (KO) mice to decipher the individual, collaborative and collective roles of Dectin-1, Dectin-2 and Mincle during systemic C. albicans infection. These studies revealed an unappreciated and profound role for CLR co-operation in anti-fungal immunity. The protective effect of multiple CLRs was markedly greater than any single receptor, and was mediated through inflammatory monocytes via recognition and phagocytosis of C. albicans, and production of C. albicans-induced cytokines and chemokines. These CLRs were dispensable for mediating similar responses from neutrophils, likely due to lower expression of these CLRs on neutrophils compared to inflammatory monocytes. Concurrent deletion of Dectin-1 and Dectin-2, or all three CLRs, resulted in dramatically increased susceptibility to systemic C. albicans infection compared to mice lacking a single CLR. Multi-CLR KO mice were unable to control fungal growth due to an inadequate early inflammatory monocyte-mediated response. In response to excessive fungal growth, the multi-CLR KO mice mounted a hyper-inflammatory response, likely leading to multiple organ failure. Thus, these data reveal a critical role for CLR co-operation in the effective control of C. albicans and maintenance of organ function during infection.


Assuntos
Candida albicans/imunologia , Candidíase/imunologia , Lectinas Tipo C/imunologia , Proteínas de Membrana/imunologia , Monócitos/imunologia , Animais , Candidíase/genética , Quimiocinas/genética , Quimiocinas/imunologia , Inflamação/genética , Inflamação/imunologia , Inflamação/patologia , Lectinas Tipo C/genética , Proteínas de Membrana/genética , Camundongos , Camundongos Knockout , Monócitos/patologia , Neutrófilos/patologia
13.
Cardiovasc Diabetol ; 20(1): 204, 2021 10 09.
Artigo em Inglês | MEDLINE | ID: mdl-34627231

RESUMO

BACKGROUND: With emerging evidence on the efficacy of adding dapagliflozin to standard care for patients with heart failure with reduced ejection fraction (HFrEF), this study assessed the cost-effectiveness of add-on dapagliflozin to standard care versus standard care alone for HFrEF from the perspective of healthcare systems in the Asia-Pacific region. METHODS: A Markov model was applied to project the outcomes of treatment in terms of lifetime medical cost and quality-adjusted life-years. The transition probabilities between health states in the model were obtained from the Dapagliflozin in Patients with Heart Failure and Reduced Ejection Fraction trial. Country-specific costs and utilities were extracted for modeling. The incremental cost-effectiveness ratio against a country-specific willingness-to-pay threshold was applied to determine the cost-effectiveness of treatment. A series of sensitivity analyses were performed to ensure the robustness of the study results. Costs are presented in 2020 United States dollars. RESULTS: The incremental cost-effectiveness ratios for add-on dapagliflozin versus standard care alone were $5277, $9980, $12,305, $16,705, and $23,227 per quality-adjusted life-year gained in Korea, Australia, Taiwan, Japan, and Singapore, respectively. When using add-on dapagliflozin to standard care versus standard care alone, ~ 100% of simulations were cost-effective at a willingness-to-pay threshold of one gross domestic product per capita of the given Asia-Pacific country; however, the probability of being cost-effective for using add-on dapagliflozin decreased when the time horizon for simulation was restricted to 18 months and when the cardiovascular mortality for the two treatments (43.8% and 33.0%, respectively) was assumed to be the same. The cost-effectiveness results were most sensitive to cardiovascular mortality of treatment. CONCLUSIONS: Adding dapagliflozin to standard care is cost-effective for HFrEF in healthcare systems in the Asia-Pacific region, which supports the rational use of dapagliflozin for HFrEF in this region.


Assuntos
Compostos Benzidrílicos/economia , Compostos Benzidrílicos/uso terapêutico , Atenção à Saúde/economia , Custos de Medicamentos , Glucosídeos/economia , Glucosídeos/uso terapêutico , Insuficiência Cardíaca Sistólica/tratamento farmacológico , Insuficiência Cardíaca Sistólica/economia , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Volume Sistólico/efeitos dos fármacos , Função Ventricular Esquerda/efeitos dos fármacos , Idoso , Ásia/epidemiologia , Austrália/epidemiologia , Compostos Benzidrílicos/efeitos adversos , Análise Custo-Benefício , Feminino , Glucosídeos/efeitos adversos , Insuficiência Cardíaca Sistólica/mortalidade , Insuficiência Cardíaca Sistólica/fisiopatologia , Custos Hospitalares , Hospitalização/economia , Humanos , Masculino , Cadeias de Markov , Modelos Econômicos , Qualidade de Vida , Anos de Vida Ajustados por Qualidade de Vida , Recuperação de Função Fisiológica , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos , Inibidores do Transportador 2 de Sódio-Glicose/economia , Fatores de Tempo , Resultado do Tratamento
14.
J Pathol ; 250(1): 55-66, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31579932

RESUMO

Peritoneal fibrosis remains a problem in kidney failure patients treated with peritoneal dialysis. Severe peritoneal fibrosis with encapsulation or encapsulating peritoneal sclerosis is devastating and life-threatening. Although submesothelial fibroblasts as the major precursor of scar-producing myofibroblasts in animal models and M2 macrophage (Mϕ)-derived chemokines in peritoneal effluents of patients before diagnosis of encapsulating peritoneal sclerosis have been identified, attenuation of peritoneal fibrosis is an unmet medical need partly because the mechanism for cross talk between Mϕs and fibroblasts remains unclear. We use a sodium hypochlorite-induced mouse model akin to clinical encapsulated peritoneal sclerosis to study how the peritoneal Mϕs activate fibroblasts and fibrosis. Sodium hypochlorite induces the disappearance of CD11bhigh F4/80high resident Mϕs but accumulation of CD11bint F4/80int inflammatory Mϕs (InfMϕs) through recruiting blood monocytes and activating local cell proliferation. InfMϕs switch to express chemokine (C-C motif) ligand 17 (CCL17), CCL22, and arginase-1 from day 2 after hypochlorite injury. More than 75% of InfMϕs undergo genetic recombination by Csf1r-driven Cre recombinase, providing the possibility to reduce myofibroblasts and fibrosis by diphtheria toxin-induced Mϕ ablation from day 2 after injury. Furthermore, administration of antibody against CCL17 can reduce Mϕs, myofibroblasts, fibrosis, and improve peritoneal function after injury. Mechanistically, CCL17 stimulates migration and collagen production of submesothelial fibroblasts in culture. By breeding mice that are induced to express red fluorescent protein in Mϕs and green fluorescence protein (GFP) in Col1a1-expressing cells, we confirmed that Mϕs do not produce collagen in peritoneum before and after injury. However, small numbers of fibrocytes are found in fibrotic peritoneum of chimeric mice with bone marrow from Col1a1-GFP reporter mice, but they do not contribute to myofibroblasts. These data demonstrate that InfMϕs switch to pro-fibrotic phenotype and activate peritoneal fibroblasts through CCL17 after injury. CCL17 blockade in patients with peritoneal fibrosis may provide a novel therapy. © 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.


Assuntos
Quimiocina CCL17/metabolismo , Fibroblastos/metabolismo , Mediadores da Inflamação/metabolismo , Ativação de Macrófagos , Macrófagos Peritoneais/metabolismo , Comunicação Parácrina , Fibrose Peritoneal/metabolismo , Peritônio/metabolismo , Animais , Proliferação de Células , Quimiocina CCL17/genética , Colágeno Tipo I/genética , Cadeia alfa 1 do Colágeno Tipo I , Modelos Animais de Doenças , Fibroblastos/patologia , Proteínas de Fluorescência Verde/genética , Proteínas de Fluorescência Verde/metabolismo , Macrófagos Peritoneais/patologia , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Fibrose Peritoneal/induzido quimicamente , Fibrose Peritoneal/genética , Fibrose Peritoneal/patologia , Peritônio/patologia , Fenótipo , Regiões Promotoras Genéticas , Transdução de Sinais , Hipoclorito de Sódio
15.
Cardiovasc Drugs Ther ; 35(2): 205-214, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32557011

RESUMO

Coronavirus disease 2019 (COVID-19) is a pandemic infection caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). COVID-19 significantly affects multiple systems including the cardiovascular system. Most importantly, in addition to the direct injury from the virus per se, the subsequent cytokine storm, an overproduction of immune cells and their activating compounds, causes devastating damage. To date, emerging anti-SARS-CoV-2 treatments are warranted to control epidemics. Several candidate drugs have been screened and are currently under investigation. These primarily include antiviral regimens and immunomodulatory regimens. However, beyond the anti-SARS-CoV-2 effects, these drugs may also have risks to the cardiovascular system, especially altering cardiac conduction. Herein, we review the cardiovascular risks of potential anti-COVID-19 drugs.


Assuntos
Antivirais/farmacologia , Tratamento Farmacológico da COVID-19 , COVID-19 , Cardiotoxicidade/prevenção & controle , Sistema Cardiovascular/efeitos dos fármacos , Fatores Imunológicos/farmacologia , SARS-CoV-2/efeitos dos fármacos , COVID-19/imunologia , Humanos , Medição de Risco
16.
Cardiovasc Drugs Ther ; 35(3): 539-547, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-32910340

RESUMO

PURPOSE: This study aimed to investigate the cost-effectiveness of low-dose rivaroxaban plus aspirin versus aspirin alone for patients with stable cardiovascular diseases in the Taiwan setting. METHODS: We constructed a Markov model to project the lifetime direct medical costs and quality-adjusted life-years of both therapies. Transitional probabilities were derived from the COMPASS trial, and the costs and utilities were obtained from the Taiwan National Health Insurance Database and published studies. One-way, scenario, subgroup, and probabilistic sensitivity analyses were performed to assess the uncertainty. Incremental cost-effectiveness ratio was presented as the outcome. The threshold of willingness-to-pay was set at US$76,368 (3 times the gross domestic product per capita of Taiwan). All analyses were operated by TreeAge 2019 and Microsoft Excel. RESULTS: The incremental cost-effectiveness ratios of rivaroxaban plus aspirin versus aspirin alone in the patients with stable cardiovascular diseases, coronary artery diseases, and peripheral artery diseases were US$83,459, US$69,852 and -US$13,823 per quality-adjusted life-year gained, respectively. The probabilistic sensitivity analyses showed that the probabilities of cost-effectiveness for the regimen with rivaroxaban among those with cardiovascular diseases and coronary artery diseases were 44.1% and 65.3% at US$76,368. CONCLUSION: Low-dose rivaroxaban plus aspirin is less likely to be a cost-effective alternative to aspirin in secondary prevention for the patients with stable cardiovascular diseases; however, among these patients, the regimen may have pharmacoeconomic incentives for the group merely having chronic coronary artery diseases from the Taiwan national payer's perspective. The pharmacoeconomic incentives are influenced by the drug price, event treatment fees, and willingness-to-pay threshold.


Assuntos
Anticoagulantes/uso terapêutico , Aspirina/uso terapêutico , Doenças Cardiovasculares/tratamento farmacológico , Rivaroxabana/uso terapêutico , Anticoagulantes/administração & dosagem , Anticoagulantes/efeitos adversos , Anticoagulantes/economia , Aspirina/administração & dosagem , Aspirina/efeitos adversos , Aspirina/economia , Doença da Artéria Coronariana/tratamento farmacológico , Análise Custo-Benefício , Relação Dose-Resposta a Droga , Quimioterapia Combinada , Inibidores do Fator Xa/economia , Inibidores do Fator Xa/uso terapêutico , Gastos em Saúde , Humanos , Cadeias de Markov , Doença Arterial Periférica/tratamento farmacológico , Anos de Vida Ajustados por Qualidade de Vida , Rivaroxabana/administração & dosagem , Rivaroxabana/efeitos adversos , Rivaroxabana/economia , Prevenção Secundária/economia , Prevenção Secundária/métodos , Taiwan
17.
Int J Mol Sci ; 22(8)2021 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-33921715

RESUMO

Millions of experimental animals are widely used in the assessment of toxicological or biological effects of manufactured nanomaterials in medical technology. However, the animal consciousness has increased and become an issue for debate in recent years. Currently, the principle of the 3Rs (i.e., reduction, refinement, and replacement) is applied to ensure the more ethical application of humane animal research. In order to avoid unethical procedures, the strategy of alternatives to animal testing has been employed to overcome the drawbacks of animal experiments. This article provides current alternative strategies to replace or reduce the use of experimental animals in the assessment of nanotoxicity. The currently available alternative methods include in vitro and in silico approaches, which can be used as cost-effective approaches to meet the principle of the 3Rs. These methods are regarded as non-animal approaches and have been implemented in many countries for scientific purposes. The in vitro experiments related to nanotoxicity assays involve cell culture testing and tissue engineering, while the in silico methods refer to prediction using molecular docking, molecular dynamics simulations, and quantitative structure-activity relationship (QSAR) modeling. The commonly used novel cell-based methods and computational approaches have the potential to help minimize the use of experimental animals for nanomaterial toxicity assessments.


Assuntos
Experimentação Animal , Animais , Nanoestruturas , Relação Quantitativa Estrutura-Atividade , Engenharia Tecidual
18.
Int Heart J ; 62(4): 944-948, 2021 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-34234073

RESUMO

Extrinsic compression of the left atrium (LA) due to esophageal achalasia has been considered a rare occurrence. Patients might present with dysphagia, dyspnea, and even hemodynamic compromise simultaneously. Prompt detection with a thorough differential diagnosis is crucial for subsequent management. In this case report, we present a patient with LA compression by esophageal achalasia and performed a literature review to gather information as regards the clinical manifestation, diagnosis, and treatment strategy of this rare disease.A 59-year-old man with intermittent palpitation, heartburn sensation, and difficulty swallowing came to our emergency department due to acute onset of chest compression and breathlessness after a large meal. As per his chest X-ray, dilated mediastinum and small gastric bubble were noted. Electrocardiogram implied left atrial enlargement, and the Holter monitor reported one episode of paroxysmal atrial fibrillation attack during his meal. Transthoracic echocardiogram showed a round-shaped, well-bordered, hyperechogenic, and heterogeneous mass compressing the LA irrespective of the systolic or diastolic phase. A chest contrast-enhanced computed tomography scan was then performed, wherein it showed diffuse esophageal dilatation with a smoothly thickening wall aligned compressing the LA. Meanwhile, the barium swallow esophagogram revealed contrast pooling at the esophagogastric junction with a bird beak shape. Accordingly, extrinsic compression of LA by esophageal achalasia was diagnosed.Esophageal achalasia compressing LA has been considered rare. Remarkably, given that a patient is presenting with dysphagia and concurrent chest tightness, palpitation, and dyspnea after swallowing food, the clinicians should keep this diagnosis in mind. Careful history review to clarify the causal relationship between the symptoms, specific findings on electrocardiogram and chest X-ray, and utilization of echocardiography and esophagography are beneficial for a prompt and accurate diagnosis.


Assuntos
Fibrilação Atrial/etiologia , Acalasia Esofágica/complicações , Átrios do Coração/diagnóstico por imagem , Ecocardiografia , Eletrocardiografia , Acalasia Esofágica/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-Idade
19.
Acta Cardiol Sin ; 37(1): 9-17, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33488023

RESUMO

SARS-CoV-2 is the virus that has caused the current coronavirus disease 2019 (COVID-19) pandemic. SARS-CoV-2 is characterized by significantly affecting the cardiovascular system of infected patients. In addition to the direct injuries caused by the virus, the subsequent cytokine storm - an overproduction of immune cells and their activating compounds - also causes damage to the heart. The development of anti-SARS-CoV-2 treatments is necessary to control the epidemic. Despite an explosive growth in research, a comprehensive review of up-to-date information is lacking. Herein, we summarize pivotal findings regarding the epidemiology, complications, and mechanisms of, and recent therapies for, COVID-19, with special focus on its cardiovascular impacts.

20.
Acta Cardiol Sin ; 37(1): 97-99, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33488032

RESUMO

COVID-19 has reached a pandemic level and affected both individual's health and global healthcare systems. Although Taiwan has encountered a less severe COVID-19 pandemic than many other countries, it has impacted the workflow of all cardiovascular examinations and procedures. Compared to before January 21st, 2020 (the date of the first confirmed COVID-19 in Taiwan), the number of patients who have received echocardiography and cardiac catheterization has since fallen. However, the number of percutaneous coronary interventions being performed has remained at the usual level. Based on our experience, we suggest that healthcare providers in Taiwan should carefully evaluate the urgency of cardiovascular procedures and deferred non-emergent procedures. Given that the pandemic has not yet plateaued, we should remain prepared for future challenges to maintain our medical service.

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