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BACKGROUND: Angiotensin receptor neprilysin inhibitor (ARNI) and sodium-glucose cotransporter 2 inhibitor (SGLT2i) are emerging medical treatments for decompensated heart failure (HF) with reduced ejection fraction. In clinical practice, the combination of ARNI and SGLT2i cannot be administered owing to the poor hemodynamic status in patients with HF with reduced ejection fraction (HFrEF). This study aimed to compare different strategies of HF management for ARNI first or SGLT2i first in such a population. METHODS: From January 2016 to December 2021, 165 patients were diagnosed with HFrEF and New York Heart Association functional class ≥II and already received optimal medical treatment. Ninety-five patients received the ARNI-first strategy, and 70 patients received the SGLT2i-first strategy according to the physician's choice. Age, sex, hemodynamic condition, etiologies of HF, comorbidities, serum creatinine, N-terminal pro-B-type natriuretic peptide (NT-ProBNP), echocardiographic parameters, and clinical outcomes were compared between the ARNI and SGLT2i-first strategy groups. RESULTS: In the SGLT2i-first group, the median interval between the addition of the second medication was longer (ARNI-first vs. SGLT2i-first; 74 [49-100] days vs. 112 [86-138] days; p = 0.044). Improvement in left ventricular ejection fraction (LVEF), change in left atrial dimension, and change in left ventricular end-diastolic and end-systolic volume (LVESV) did not differ between the two groups. The incidence of HF hospitalization, cardiovascular mortality, and all-cause mortality did not differ between the two groups. A non-significant trend of lower NT-proBNP levels (ARNI-first vs. SGLT2i-first; 1383 [319-2507] pg/mL vs. 570 [206-1314] pg/mL; p = 0.055) and significantly higher discontinuation rate of diuretic agents (ARNI-first vs. SGLT2i- first; 6.8% vs. 17.5%; p = 0.039) were noted in the SGLT2i-first group. When early combination (≤14D) compared to late combination (>14D), better positive remodeling of LVESV presented significantly in early combination subgroups. CONCLUSIONS: In patients with symptomatic HFrEF, SGLT2i-first strategy may provide a higher possibility of discontinuing diuretic agents than the ARNI-first strategy. Changes in LV performance, progression of renal function, and clinical outcomes did not differ between the two groups. Early combination (≤14D) provided better LV remodeling.
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Insuficiência Cardíaca , Humanos , Antagonistas de Receptores de Angiotensina/uso terapêutico , Antagonistas de Receptores de Angiotensina/farmacologia , Anti-Hipertensivos/farmacologia , Anti-Hipertensivos/uso terapêutico , Diuréticos/farmacologia , Diuréticos/uso terapêutico , Combinação de Medicamentos , Glucose/farmacologia , Insuficiência Cardíaca/diagnóstico , Neprilisina/farmacologia , Neprilisina/uso terapêutico , Sódio/farmacologia , Sódio/uso terapêutico , Inibidores do Transportador 2 de Sódio-Glicose/farmacologia , Volume Sistólico , Tetrazóis/farmacologia , Tetrazóis/uso terapêutico , Resultado do Tratamento , Valsartana/farmacologia , Valsartana/uso terapêutico , Função Ventricular EsquerdaRESUMO
Although androgen deprivation therapy (ADT) has been proposed to be associated with a higher risk of venous thromboembolisms (VTEs), whether gonadotropin-releasing hormones (GnRHs), such as both agonists and antagonists, are also associated with VTEs remain unclear. Using the Taiwan Cancer Registry (TCR) linked with the National Health Insurance Research Database, we identified patients diagnosed with prostate cancer from 2008 to 2015. Patients who received GnRH were 1:1 propensity score matched with non-GnRH users by age and cancer stage at diagnosis and clinical stage. Cox regression analysis was applied to estimate the incidences of VTEs with death as a competing event at the 5-year follow-up. The VTE incidence among GnRH users was 1.13% compared with 0.98% among non-users. After adjusting with potential confounding factors, the risk of VTEs showed borderline statistical significance among GnRH users and non-users. Notably, in the subgroup analysis among patients receiving GnRH therapy, those younger than 70 years old or at an earlier stage (stage I/II) were at a higher risk of VTEs. Different from previous studies, our findings highlighted critical concerns regarding the cardiac safety of GnRH therapies in prostate cancer patients at a relatively younger age or at an earlier stage.
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PURPOSE: Androgen deprivation therapy (ADT) includes bilateral orchiectomy or long-acting gonadotropin-releasing hormone (GnRH) agonists/antagonists. It remains controversial with respect to ADT associated cardiovascular outcomes. Hereby, we compared the risk of major adverse cardiovascular and cerebrovascular events (MACCEs) in patients with prostate cancer receiving either surgical castration or GnRH therapies. MATERIALS AND METHODS: Using the Taiwan Cancer Registry and Taiwan's National Health Insurance Research Database, we identified 8,413 patients receiving GnRH therapies compared with 694 receiving surgical castration from 2008 to 2017. The median followup duration was 3 years. RESULTS: The crude incidences of 3-year mortality and MACCEs were 19.90% vs 26.51% and 8.23% vs 8.65% in patients receiving GnRH therapies or surgical castration, respectively. After adjusting for age, cancer stage and comorbidities, despite no significant differences in MACCEs between groups there was a slight increase in the incidence of acute myocardial infarction (AMI) in patients receiving surgical castration compared with those receiving GnRH therapies. The mortality adjusted hazard ratios of MACCEs and AMI among patients receiving surgical castration were 1.11- and 1.8-fold higher than those receiving GnRH therapies. Notably, in subgroup analysis regarding cancer stage, patients with cancer stage IV showed the most significantly increasing risk of AMI in those receiving surgical castration compared with GnRH therapies. CONCLUSIONS: Collectively, we indicated an increased risk of AMI in patients with prostate cancer, especially in patients receiving surgical castration rather than those receiving GnRH therapies. Our findings highlight concerns regarding the cardiac safety of surgical castration compared with GnRH therapies.
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Antagonistas de Androgênios/efeitos adversos , Antineoplásicos Hormonais/efeitos adversos , Cardiotoxicidade/etiologia , Doenças Cardiovasculares/etiologia , Orquiectomia/efeitos adversos , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/cirurgia , Cardiotoxicidade/epidemiologia , Cardiotoxicidade/mortalidade , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/mortalidade , Humanos , Masculino , Complicações Pós-Operatórias/etiologia , Fatores de Risco , Taiwan/epidemiologiaRESUMO
Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a rare complication after vaccination of Oxford-AstraZeneca coronavirus disease 2019 (COVID-19) vaccine (AZD1222) or Janssen COVID-19 vaccine. It makes a rare complication of thrombosis at common and/or uncommon organs with thrombocytopenia after COVID-19 vaccination four to 28 days later and most patients were younger than 60 years of age. We reported the case of a 75-year-old female with end-stage renal disease who received regular hemodialysis. She received Oxford-AstraZeneca COVID-19 vaccination eight days ago and then she suffered from intermittent chest tightness and epigastric pain with tarry stool passage for two days. Severe thrombocytopenia with elevated D-dimer value was noted and computed tomography of the chest showed azygos vein thrombosis. Elevated cardiac enzyme with ST-T change in 12-lead electrocardiogram was also noted. For positive anti-platelet factor 4 antibodies, VITT with myocardial infarction and azygos vein thrombosis was diagnosed.
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How renal function influences post-acute myocardial infarction (AMI) cardiac remodeling and outcomes remains unclear. This study evaluated the impact of levels of renal impairment on drug therapy, echocardiographic parameters, and outcomes in patients with AMI undergoing percutaneous coronary intervention (PCI). A total of 611 patients diagnosed with AMI underwent successful PCI, and two echocardiographic examinations were performed within 1 year after AMI. Patients were categorized according to Group 1: severely impaired estimated glomerular filtration rate (eGFR)<30, Group 2: mildly impaired 30≤eGFR<60, Group 3: potentially at risk 60≤eGFR<90 and normal eGFR≥90 ml/min/1.73 m2. During the 5-year follow-up period, the primary endpoints were cardiovascular mortality and outcomes. Patients with worse renal function (eGFR<30) were older and had a higher prevalence of hypertension and diabetes, but relatively few were smokers or had hyperlipidemia. Despite more patients with lesions of the left anterior descending artery, those with worse renal function received suboptimal guideline-directed medical therapy (GDMT). Notably, patients with worse renal function presented with worse left ventricular function at baseline and subsequent follow-up. Kaplan-Meier analysis revealed increased cardiovascular death, development of heart failure, recurrent AMI and revascularization in patients with worse renal function. Notably, as focusing on patients with ST elevation MI, the similar findings were observed. In multivariable Cox regression, impaired renal function showed the most significant hazard ratio in cardiovascular death. Collectively, in AMI patients receiving PCI, outcome differences are renal function dependent. We found that patients with worse renal function received less GDMT and presented with worse cardiovascular outcomes. These patients require more attention.
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Insuficiência Cardíaca/epidemiologia , Infarto do Miocárdio/terapia , Intervenção Coronária Percutânea , Insuficiência Renal/epidemiologia , Remodelação Ventricular/fisiologia , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Fármacos Cardiovasculares/uso terapêutico , Terapia Combinada/métodos , Feminino , Seguimentos , Taxa de Filtração Glomerular/fisiologia , Insuficiência Cardíaca/etiologia , Humanos , Estimativa de Kaplan-Meier , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/complicações , Infarto do Miocárdio/mortalidade , Período Pós-Operatório , Prevalência , Insuficiência Renal/complicações , Insuficiência Renal/fisiopatologia , Fatores de Risco , Resultado do TratamentoRESUMO
OBJECTIVE: Varicose veins (VVs) are common and although considered benign may cause morbidity. However, the association between VV severity and cardiovascular and mortality risks remains unknown. The aim of this study was to investigate the factors associated with overall mortality in patients with VV. METHODS: A total of 4644 patients with newly diagnosed VV between 1999 and 2013 were identified from Taiwan's National Health Insurance Database. VV severity was classified from grade 1 to 3 according to the presentation of ulcers or inflammation. Moreover, 9497, 2541 and 5722 age-matched, sex-matched and chronic cardiovascular risk factor-matched controls, as assessed based on propensity score, were separately selected for three grading VV groups. Enrolled patients were analysed using conditional Cox proportional hazards regression analysis to estimate risk of mortality and major adverse cardiovascular events (MACEs) in the VV and control groups. RESULTS: Most patients with VV were free from systemic disease. However, compared with matched controls, patients with VV showed a 1.37 times increased risk of mortality (95% CI 1.19 to 1.57; p<0.0001). Compared with matched controls, older (age â§65 years) (adjusted HR: 1.38; 95% CI 1.17 to 1.62; p=0.0001) and male patients with VV (adjusted HR 1.41; 95% CI 1.18 to 1.68; p=0.0001) showed increased risk of mortality. Furthermore, compared with controls, patients with VV showed 2.05 times greater risk of MACE. Compared with matched controls, population at grade 3 increased 1.83 times risk of mortality and 2.04 to 38.42 times risk of heart failure, acute coronary syndrome, ischaemic stroke and venous thromboembolism. CONCLUSIONS: This nationwide cohort study demonstrated that patients with VV are at a risk of cardiovascular events and mortality. Our findings suggest that presence of VV warrants close attention in terms of prognosis and treatment.
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Varizes/mortalidade , Síndrome Coronariana Aguda/epidemiologia , Fatores Etários , Idoso , Estudos de Casos e Controles , Estudos de Coortes , Insuficiência Cardíaca/epidemiologia , Humanos , AVC Isquêmico/epidemiologia , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Fatores Sexuais , Taiwan/epidemiologia , Tromboembolia Venosa/epidemiologiaRESUMO
OBJECTIVE: Atrial fibrillation (AF) is the most common cardiac complication of thyrotoxicosis and is strongly implicated in thromboembolic events. However, the incidence of stroke in thyrotoxic AF remains unclear. Herein, we aimed to investigate the risks of mortality and ischaemic stroke between patients with thyrotoxic AF and nonthyrotoxic AF. DESIGNS AND METHODS: From Taiwan's National Health Insurance Research Database, 1868 patients with the concomitant diagnoses of AF and thyrotoxicosis identified between 2001 and 2010 were compared to 7472 patients with nonthyrotoxic AF using propensity score matching for age, sex and comorbidities. RESULTS: There was no significant difference in either CHA2 DS2 -VASc score or anticoagulant usage between the groups. Alternatively, the thyrotoxic group contained more ß-blocker/digoxin users, whereas the nonthyrotoxic group contained more statin users. Patients with thyrotoxic AF exhibited lower risks of all-cause mortality (HR: 0.66, CI: 0.59-0.73, P < .0001) and ischaemic stroke (HR: 0.73, CI: 0.64-0.84, P < .0001) than those with nonthyrotoxic AF, especially thyrotoxic patients with CHA2 DS2 -VASc scores ≥1. Comorbidities, including diabetes, hyperlipidaemia, hypertension and coronary artery disease, contributed to all-cause mortality in patients with nonthyrotoxic AF; however, this effect was diminished in thyrotoxic AF. CONCLUSIONS: Patients with thyrotoxicosis and AF have a lower risk of stroke than patients with nonthyrotoxic AF. Treatment for thyrotoxicosis is also crucial as the prescription of anticoagulants based on CHA2DS2-VASc scores.
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Fibrilação Atrial/epidemiologia , Isquemia Encefálica/epidemiologia , Acidente Vascular Cerebral/epidemiologia , Tireotoxicose/epidemiologia , Adolescente , Adulto , Idoso , Fibrilação Atrial/etiologia , Estudos de Casos e Controles , Feminino , Hemorragia/epidemiologia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de Doença , Tireotoxicose/complicações , Adulto JovemRESUMO
Expectations substantially influence pain perception, but the relationship between positive and negative expectations remains unclear. Recent evidence indicates that the integration between pain-related expectations and prediction errors is crucial for pain perception, which suggests that aversive prediction error-associated regions, such as the anterior insular cortex (aIC) and rostral anterior cingulate cortex (rACC), may play a pivotal role in expectation-induced pain modulation and help to delineate the relationship between positive and negative expectations. In a stimulus expectancy paradigm combining fMRI in healthy volunteers of both sexes, we found that, although positive and negative expectations respectively engaged the right aIC and right rACC to modulate pain, their associated activations and pain rating changes were significantly correlated. When positive and negative expectations modulated pain, the right aIC and rACC exhibited opposite coupling with periaqueductal gray (PAG) and the mismatch between actual and expected pain respectively modulated their coupling with PAG and thalamus across individuals. Participants' certainty about expectations predicted the extent of pain modulation, with positive expectations involving connectivity between aIC and hippocampus, a region regulating anxiety, and negative expectations engaging connectivity between rACC and lateral orbitofrontal cortex, a region reflecting outcome value and certainty. Interestingly, the strength of these certainty-related connectivities was also significantly associated between positive and negative expectations. These findings suggest that aversive prediction-error-related regions interact with pain-processing circuits to underlie stimulus expectancy effects on pain, with positive and negative expectations engaging dissociable but interrelated neural responses that are dependently regulated by individual certainty about expectations.SIGNIFICANCE STATEMENT Positive and negative expectations substantially influence pain perception, but their relationship remains unclear. Using fMRI in a stimulus expectancy paradigm, we found that, although positive and negative expectations engaged separate brain regions encoding the mismatch between actual and expected pain and involved opposite functional connectivities with the descending pain modulatory system, they produced significantly correlated pain rating changes and brain activation. Moreover, participants' certainty about expectations predicted the magnitude of both types of pain modulation, with the underlying functional connectivities significantly correlated between positive and negative expectations. These findings advance current understanding about cognitive modulation of pain, suggesting that both types of pain modulation engage different aversive prediction error signals but are dependently regulated by individual certainty about expectations.
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Antecipação Psicológica , Encéfalo/fisiopatologia , Percepção da Dor , Adulto , Encéfalo/diagnóstico por imagem , Mapeamento Encefálico , Sinais (Psicologia) , Feminino , Giro do Cíngulo/diagnóstico por imagem , Hipocampo/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética , Masculino , Dor/diagnóstico por imagem , Dor/fisiopatologia , Dor/psicologia , Medição da Dor , Substância Cinzenta Periaquedutal/diagnóstico por imagem , Córtex Pré-Frontal/diagnóstico por imagem , Tálamo/diagnóstico por imagem , Adulto JovemRESUMO
Radial artery occlusion (RAO) occurs in 2% to 18% of patients after transradial access (TRA) cardiac catheterization. Using a kaolin-filled pad (QuikClot) reduces compression time during TRA and might reduce RAO. We examined the RAO risk with the kaolin-filled pad after TRA cardiac catheterization.This was a prospective cross-sectional study of 260 patients who underwent TRA cardiac catheterization in a cardiac ward of a Medical Center from 2012 to 2016. Patients were randomly assigned to 1 of 2 groups: the case group (nâ=â130) was postoperatively treated with a kaolin-filled pad, and the control group (nâ=â130) was treated with conventional hemostasis. Color duplex ultrasound was used to evaluate the 24-hour and 1-month postoperative radial artery flow velocity, diameter, patency, and RAO risk.RAO risk was not significantly different between the case and control groups after 24âhours (4.6% vs 5.4%, Pâ=â.776) or after 1 month (5.4% vs 6.1%, Pâ=â.789), regardless of whether it was a first TRA cardiac catheterization (after 24âhours [Pâ=â.153] or after 1month [Pâ=â.617], respectively) or a repeated TRA cardiac catheterization (after 24âhours [Pâ=â.754] or after 1month [Pâ=â.753], respectively).Using a kaolin-filled pad after TRA cardiac catheterization did not significantly reduce RAO risk compared with conventional hemostasis.
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Arteriopatias Oclusivas/etiologia , Cateterismo Cardíaco/efeitos adversos , Caulim/administração & dosagem , Artéria Radial/cirurgia , Grau de Desobstrução Vascular/efeitos dos fármacos , Idoso , Antidiarreicos/administração & dosagem , Arteriopatias Oclusivas/epidemiologia , Arteriopatias Oclusivas/prevenção & controle , Cateterismo Periférico/efeitos adversos , Estudos Transversais , Feminino , Técnicas Hemostáticas , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Artéria Radial/efeitos dos fármacos , Medição de Risco/métodos , Ultrassonografia Doppler DuplaRESUMO
BACKGROUND: The outcome of pulmonary hypertension (PH) mainly depends on the development of right ventricular (RV) dysfunction, and survival among patients with different etiologies of PH varies. Chronic hypoxia is a major cause of secondary PH, however the mechanisms of its associated RV dysfunction are largely unknown. Herein, we studied the role of microRNA-21 (miR-21) in hypoxia-induced RV dysfunction. METHODS: In this longitudinal, prospective study, we enrolled 41 patients with hypoxia-induced PH. Echocardiography was conducted and circulating miR-21 was measured. The expression of miR-21 was also evaluated in hypoxia-treated human pulmonary microvascular endothelial cells (HPECs) and conditioned media. Through the over-expression of miR-21 in H9C2 cells, we further identified crosstalk between the pulmonary circulation and RV. RESULTS: Among the studied patients, 10 developed RV dysfunction. Notably, the expression of circulating miR-21 was correlated with the severity of RV dysfunction. Likewise, miR-21 was up-regulated in the hypoxia-treated HPECs and its conditioned media in a time-dependent manner. I addition, hypertrophic changes were observed in the hypoxia-treated HPECs. The up-regulation of heart failure-associated markers in H9C2 cells over-expressing miR-21 implied the influence of pulmonary circulatory miR-21 on RV function. CONCLUSIONS: The expression of systemic and pulmonary miR-21 is associated with the severity of RV dysfunction in patients with hypoxia-induced PH.
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Defective renal salt and water excretion, together with increased salt intake, frequently contributes to hypertension. Recent studies indicate that Ste20 family kinases, such as proline-alanine-rich Ste20-related kinase (SPAK) and oxidative stress-response protein 1 (OSR1), are regulators of cell volume, ion transport, and hypertension. The aim of this study was to investigate whether mammalian sterile 20-like protein kinase 3 (MST3), which is also a stress-regulated kinase, is involved in the development of hypertension. MST3 expression was compared in Wistar-Kyoto (WKY) and spontaneously hypertensive rat (SHR) kidneys. MST3 expression was markedly reduced in principal cells of the collecting ducts from the renal inner medulla of SHR. The downregulation of MST3 expression was observed before and after the onset of hypertension in SHR. Mice fed high-salt diets (HS) exhibited a significant increase in MST3 protein level. This is the first study reporting that MST3, a Ste20-like kinase, exerts a conserved regulatory role in sodium homeostasis after high-salt diet and in the development of hypertension.
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Pressão Sanguínea/genética , Homeostase/genética , Hipertensão/genética , Proteínas Serina-Treonina Quinases/genética , Desequilíbrio Hidroeletrolítico/genética , Animais , Cães , Regulação para Baixo , Expressão Gênica , Hipertensão/metabolismo , Túbulos Renais Coletores/citologia , Túbulos Renais Coletores/metabolismo , Células Madin Darby de Rim Canino , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Ratos , Ratos Endogâmicos SHR , Ratos Endogâmicos WKY , Sódio/metabolismo , Sódio na Dieta/administração & dosagemRESUMO
Bioresorbable vascular scaffold (BVS) implantation has been shown to be safe in patients with stable coronary disease, and effective against the thrombotic lesion and the in-stent restenosis (ISR) of the drug-eluting stent (DES). BVSs have the advantages of a snow racket concept, positive vessel remodeling, and better conformability compared with DES in acute coronary syndrome (ACS). We report on a young patient with ST-elevation myocardial infarction (STEMI) who presented to our emergency department arising from very late stent thrombosis (VLST) of a 2.5 × 28 mm paclitaxel-eluting stent (Coroflex® Please) three years after its implantation. After the patient was treated with balloon dilation, intravascular ultrasound (IVUS) revealed a short segment of a guide wire outside the DES mesh. Two BVSs were implanted to prevent a DES recoil. Post-scaffold-implantation IVUS showed adequately expanded strut of BVSs. Six months later, optical coherence tomography (OCT) revealed that some segments of the scaffold had been absorbed and that there was no in-scaffold restenosis. The patient had not complained about angina during the out-patient clinic follow-up. This is the first report of successful BVS implantation for a STEMI patient attributable to DES VLST.
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BACKGROUND: As cancer therapies have improved, patient life spans have been extended but quality of life has been threatened by chemotherapy induced cardiotoxicity. Most cardiac complications remain unobserved until specific symptoms develop. Speckle-tracking echocardiography is a sensitive imaging modality in detecting early occult myocardial dysfunction. METHODS: A total number of 35 patients newly diagnosed with breast cancer and preparing for epirubicin therapy were prospectively recruited. Echocardiography, including speckle-tracking echocardiography, was performed sequentially at baseline (T1), after the first cycle (T2) and after the third cycle (T3) of epirubicin. At each visit, the severity of dyspnea was evaluated by the assessment scale. RESULTS: Compared with the baseline, right ventricular longitudinal strain (RVLS_FW) at T2 significantly declined (-22.49 ± 4.97 vs. -18.48 ± 4.46, p = 0.001), which was also positively associated with the development of dyspnea (R2 = 0.8, p = 0.01). At T3, both the left ventricular global longitudinal strain and RVLS_FW were significantly impaired (-21.4 ± 4.12 vs. -16.94 ± 6.81%; -22.49 ± 4.97 vs. -16.86 ± 7.27%, p = 0.01; 0.001, respectively). Also, the accumulating dose of epirubicin positively correlated with the development of dyspnea (R2 = 0.38, p = 0.04) and the decline of RVLS_FW (R2 = 0.53, p = 0.02). Notably, compared with the other echocardiographic parameters only RVLS_FW at the early stage (T2) significantly correlated with the development of dyspnea (odds ratio: 1.84, 95% confidence interval: 1.22-2.78, p = 0.04). CONCLUSIONS: RVLS_FW sensitively predicts dyspnea development in breast cancer patients receiving epirubicin therapy. However, larger scale studies are required to validate its role in long-term patient survival.
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The yeast Ste20 (sterile) protein kinase, which is a serine/threonine kinase, responds to the stimulation of the G proteincoupled receptor (GPCR) pheromone receptor. Ste20 protein kinase serves as the critical component that links signaling from the GPCR/G proteins to the mitogen-activated protein kinase (MAPK) cascade in yeast. The yeast Ste20p functions as a MAP kinase kinase kinase kinase (MAP4K) in the pheromone response. Ste20-like kinases are structurally conserved from yeast to mammals. The mechanism by which MAP4K links GPCR to the MAPK pathway is less clearly defined in vertebrates. In addition to MAP4K, the tyrosine kinase cascade bridges G proteins and the MAPK pathway in vertebrate cells. Mammalian Ste20 Kinase 3 (MST3) has been categorized into the Ste20 family and has been reported to function in the regulation of cell polarity and migration. However, whether MST3 tyrosine phosphorylation regulates diverse signaling pathways is unknown. In this study, the tyrosine phosphatase inhibitor pervanadate was found to induce MST3 tyrosine phosphorylation in intact cells, and the activity of tyrosine-phosphorylated MST3 was measured. This tyrosine-directed phosphorylation was independent of MST3 activity. Parameters including protein conformation, Triton concentration and ionic concentration influenced the sensitivity of MST3 activity. Taken together, our data suggests that the serine/threonine kinase MST3 undergoes tyrosinedirected phosphorylation. The tyrosine-phosphorylated MST3 may create a docking site for the structurally conserved SH2/SH3 (Src Homology 2 and 3) domains within the Src oncoprotein. The unusual tyrosinephosphorylated MST3 may recruit MST3 to various signaling components.
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Inibidores Enzimáticos/farmacologia , Proteínas Serina-Treonina Quinases/genética , Tirosina/metabolismo , Vanadatos/farmacologia , Sequência de Aminoácidos , Animais , Cães , Ensaios Enzimáticos , Regulação da Expressão Gênica , Células HEK293 , Humanos , Cinética , Células Madin Darby de Rim Canino , Concentração Osmolar , Fosforilação/efeitos dos fármacos , Conformação Proteica , Proteínas Serina-Treonina Quinases/metabolismo , Transdução de SinaisRESUMO
Intra-aortic balloon pumping (IABP) is widely used for hemodynamic support in critical patients with cardiogenic shock (CS). We examined whether the in-hospital mortality of patients in Taiwan treated with IABP has recently declined. We used Taiwan's National Health Insurance Research Database to retrospectively review the in-hospital all-cause mortality of 9952 (7146 men [71.8%]) 18-year-old and older patients treated with IABP between 1998 and 2008. The mortality rate was 13.84% (n = 1377). The urbanization levels of the hospitals, and the number of days in the intensive care unit, of hospitalization, and of IABP treatment, and prior percutaneous coronary intervention (PCI) were associated with mortality. Seven thousand six hundred thirty-five patients (76.72%) underwent coronary artery bypass grafting (CABG) surgery, and 576 (5.79%) underwent high-risk PCI with IABP treatment. The number of patients treated with IABP significantly increased during this decade (ptrend < 0.0001), the in-hospital all-cause mortality for patients treated with IABP significantly decreased (ptrend = 0.0243), but the in-hospital all-cause mortality of patients who underwent CABG and PCI plus IABP did not decrease. In conclusion, the in-hospital mortality rate of IABP treatment decreased annually in Taiwan during the study period. However, high-risk patients who underwent coronary revascularization with IABP had a higher and unstable in-hospital mortality rate.
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Doenças Cardiovasculares/mortalidade , Doenças Cardiovasculares/cirurgia , Mortalidade Hospitalar/tendências , Balão Intra-Aórtico/estatística & dados numéricos , Adulto , Idoso , Idoso de 80 Anos ou mais , Ponte de Artéria Coronária/efeitos adversos , Ponte de Artéria Coronária/mortalidade , Feminino , Hospitalização/estatística & dados numéricos , Hospitalização/tendências , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/mortalidade , Infarto do Miocárdio/cirurgia , Intervenção Coronária Percutânea/efeitos adversos , Intervenção Coronária Percutânea/mortalidade , Estudos Retrospectivos , Choque Cardiogênico/mortalidade , Choque Cardiogênico/cirurgia , Taiwan/epidemiologiaRESUMO
BACKGROUND: Coronary artery complications are the predominant causes of morbidity and mortality in childhood Kawasaki disease (KD). The aim of this study was to investigate the incidence of coronary artery complications and cardiac sequelae in pediatric patients with KD. METHODS: Using the Taiwan National Health Insurance (NHI) database from 1997 to 2008, records of patients with KD were reviewed retrospectively, utilizing the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) code 446.1 in pediatric patients aged 18 years or under. The ICD-9CM was also used to identify the outcomes for coronary artery complications (ICD-9-CM codes 410-414), including coronary artery aneurysm (CAA) (ICD-9-CM code 414.11). RESULTS: From the records of pediatric patients with KD admitted to hospitals between 1997 and 2004, 8148 patients without any history of coronary artery complications before KD were selected for study. Of those patients, 694 patients (8.5%) were followed-up until the end of 2008 to estimate the incidence of coronary artery complications. The ratio of boys to girls with coronary artery complications was 1.84, and the incidence of coronary artery complications was 11.53 per 1,000 person-years. Among the 8148 pediatric patients with KD, 12 patients (0.15%; 8 boys and 4 girls) had myocardial infarction, and 20 patients (0.25%; 12 boys and 8 girls) died during follow-up. CONCLUSIONS: This study is the first report regarding the incidence of coronary artery complications in KD children aged 18 years or younger. The incidence of coronary artery complications was higher as patients progressed in age, and increased by year. However, major complications such as death and myocardial infarction did not frequently occur. KEY WORDS: Cardiac sequelae; Coronary artery complications; Incidence; Kawasaki disease.