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BACKGROUND: Sodium-glucose cotransporter-2 inhibitors, such as empagliflozin, are pivotal therapies for heart failure. However, the effect of empagliflozin on doxorubicin-related cardiac dysfunction remains unclear. METHODS: Human induced pluripotent stem cell- and embryonic stem cell-derived cardiomyocytes were used to investigate the direct effect of empagliflozin on human cardiomyocytes. Then, the c-Jun amino-terminal kinases (JNK) inhibitor SP600125 was administered to the doxorubicin cardiotoxicity model in vitro and in vivo to investigate the role of JNK in empagliflozin. RESULTS: In human stem cell-derived cardiomyocytes, pretreatment with empagliflozin attenuated doxorubicin-induced cleavage of caspase 3 and other apoptosis markers. Empagliflozin significantly attenuated doxorubicin-induced phosphorylation of JNK and p38. Inhibiting the phosphorylation of JNK (SP600125) or STAT3 attenuated doxorubicin-induced apoptosis, but inhibiting the phosphorylation of p38 did not. SP600125 inhibits the phosphorylation of STAT3 (S727), and a STAT3 (Y705) inhibitor also inhibits the phosphorylation of JNK. Empagliflozin and SP600125 attenuated doxorubicin-induced increases in reactive oxygen species (ROS) and decreases in oxidized nicotinamide adenine dinucleotide (NAD+). In animal studies, empagliflozin and SP600125 attenuated doxorubicin-induced cardiac dysfunction and fibrosis. CONCLUSIONS: Empagliflozin attenuated doxorubicin-induced apoptosis by inhibiting the phosphorylation of JNK and its downstream signaling pathways, including ROS and NAD+.
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Apoptosis , Compuestos de Bencidrilo , Cardiotoxicidad , Doxorrubicina , Glucósidos , Miocitos Cardíacos , Glucósidos/farmacología , Compuestos de Bencidrilo/farmacología , Doxorrubicina/toxicidad , Doxorrubicina/efectos adversos , Cardiotoxicidad/tratamiento farmacológico , Cardiotoxicidad/prevención & control , Miocitos Cardíacos/efectos de los fármacos , Miocitos Cardíacos/metabolismo , Miocitos Cardíacos/patología , Humanos , Animales , Apoptosis/efectos de los fármacos , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Inhibidores del Cotransportador de Sodio-Glucosa 2/farmacología , Masculino , Especies Reactivas de Oxígeno/metabolismo , Antracenos/farmacología , Proteínas Quinasas JNK Activadas por Mitógenos/metabolismo , Fosforilación/efectos de los fármacos , Ratones , Células Madre Pluripotentes Inducidas/efectos de los fármacos , Células Madre Pluripotentes Inducidas/metabolismo , Ratones Endogámicos C57BLRESUMEN
BACKGROUND: Vascular access dysfunction is a great burden for hemodialysis patients. Early intervention of a dysfunctional arteriovenous shunt is associated with higher technical success and may improve midterm patency. This trial aimed to estimate the feasibility of a new system, the "rapid intervention team" (RIT) strategy. METHODS: We recruited hemodialysis patients who visited our hospital because of arteriovenous shunt dysfunction or failure to undergo an RIT strategy from September 1, 2019 to December 31, 2022. In addition, we included a control group comprising patients who underwent percutaneous intervention for arteriovenous shunt dysfunction or failure before this strategy was implemented from February 1, 2017 to December 31, 2022. Case number, time to intervention, all-cause mortality, cumulative survival rate, and number of patients who required temporary dialysis catheter insertion and recreation were compared between the two groups. The primary endpoints were double-lumen insertion, a composite outcome involving permanent catheter insertion, and the need for recreation. The secondary endpoint was all-cause mortality. RESULTS: We enrolled 1054 patients, including 544 (51.6%) and 510 (48.4%) in the RIT and control groups, respectively. Even with the coronavirus disease of 2019 (COVID-19) pandemic, the number of cases significantly increased after the implementation of the RIT strategy (from 216 in 2019 to 828 in 2022, p for trend <0.001). The RIT group had a shortened time to intervention ( p for trend <0.001). The implementation of the RIT strategy was significantly associated with a reduced risk of insertion of a temporary double-lumen catheter and recreation of vascular access (1% vs 6% and 1% vs 28%, respectively; both p < 0.01). The cumulative survival rate was not significantly different between the RIT and control groups ( p = 0.16). CONCLUSION: The implementation of the RIT strategy improves the quantity and quality of percutaneous transluminal intervention for arteriovenous shunt dysfunction or failure in patients undergoing hemodialysis.
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Derivación Arteriovenosa Quirúrgica , Diálisis Renal , Humanos , Masculino , Femenino , Persona de Mediana Edad , Anciano , COVID-19RESUMEN
BACKGROUND: The second-and third-generation drug-eluting stents (DESs) in-stent restenosis (ISR) genetic risk score (GRS) model has been previously validated. However, the model has not been validated in geriatric patients. Therefore, we conducted this study to test the feasibility of the DES-ISR GRS model in geriatric patients with coronary artery disease (CAD) in Taiwan. METHODS: We conducted a retrospective, single-center cohort study and included geriatric patients (age ≥ 65 years) with CAD and second-or third-generation DES(s) deployment. Patients undergoing maintenance dialysis were excluded. ISR was defined as ≥ 50% luminal narrowing on the follow-up coronary arteriography. The DES-ISR GRS model included five selected exonic single-nucleotide polymorphisms (SNPs): CAMLG, GALNT2, C11orf84, THOC5, and SAMD11. The GRS was defined as the sum of the five selected SNPs for the risk allele. RESULTS: We enrolled 298 geriatric patients from January 2010 and December 2019 in this study. After propensity score matching, there were 192 geriatric patients with CAD in the final analysis, of which 32 patients had ISR. Patients were divided into two groups based on their GRS values: low (0-2) and high (≥ 3) GRS. A high GRS was significantly associated with DES-ISR in geriatric patients. CONCLUSION: Those geriatric patients with a high GRS had significantly higher second-or third-generation DES ISR rates. The five SNP-derived DES-ISR GRS model could provide genetic information for interventional cardiologists to treat geriatric patients with CAD. TRIAL REGISTRATION: The primary study protocol was registered with clinicaltrials.org. with registration number: NCT03877614; on March 15, 2019. ( http://clinicaltrials.gov/ct2/show/NCT03877614 ).
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Enfermedad de la Arteria Coronaria , Reestenosis Coronaria , Stents Liberadores de Fármacos , Humanos , Anciano , Estudios Retrospectivos , Estudios de Cohortes , Reestenosis Coronaria/terapia , Resultado del Tratamiento , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Enfermedad de la Arteria Coronaria/genética , Enfermedad de la Arteria Coronaria/terapia , Factores de Riesgo , Proteínas NuclearesRESUMEN
OBJECTIVE: Thrombus features on computed tomography (CT) play a key role in distinguishing between acute and chronic pulmonary embolisms (PEs). However, the thrombus features of subacute PE are largely unknown. METHODS: This retrospective study included 358 patients (age, 65 ± 16 years; percentage of men, 38%) diagnosed with PE from 2008 to 2019. The patients were divided into a study group and a verification group. Thrombus features that changed over time were determined in the study group according to the time of PE occurrence. Next, we determined the thrombus features of subacute PE and verified them in the verification group. Finally, we compared clinical deterioration and the 1-month mortality rate between the patients with acute and subacute PEs. RESULTS: The main feature of eccentric thrombi that changed over time was the angle with the arterial wall, whereas those of centric thrombi were recanalization and heterogeneity. Taken together, the features of subacute PE were determined to be an obtuse angle with the arterial wall, recanalization, and heterogeneity. The accuracy of these features in identifying subacute PE was 94% during verification. Between the patients with acute and subacute PEs, there was no significant difference in clinical deterioration (19% vs 14%; P = .32) or the 1-month mortality rate (15% vs 8%; P = .11). With multivariate analysis, subacute events were also not associated with clinical deterioration (P = .8) or the 1-month mortality rate (P = .11). CONCLUSIONS: We determined the time trend of thrombus features on CT in patients with PE and found that these features can improve the identification of subacute events. Patients with acute and subacute PEs do not have different risks of clinical deterioration and 1-month mortality.
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Deterioro Clínico , Embolia Pulmonar , Trombosis , Masculino , Humanos , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Estudios Retrospectivos , Embolia Pulmonar/diagnóstico por imagen , Embolia Pulmonar/terapia , Tomografía Computarizada por Rayos X/métodos , Trombosis/diagnóstico por imagen , Trombosis/terapiaRESUMEN
OBJECTIVE: Endovascular intervention for thrombosed aneurysmal arteriovenous fistula (AVF) is still a challenge. Manual compression technique (MCT)-assisted angioplasty may be helpful, but there is no evidence or data to support it. METHODS: From January 2018 to May 2021, patients with thrombosed aneurysmal AVFs were retrospectively enrolled. The patients were separated into the MCT group or the traditional group according to the procedure received. Technical failure, clinical failure, 90-day patency, and safety were analyzed. RESULTS: A total of 159 cases (64 ± 12 years old, 60% male) were enrolled, of which 87 cases received MCT and 72 underwent traditional angioplasty. No technical failure was observed in the MCT group, while five technical failures were observed in the traditional group (0% vs. 7%, p = 0.02). There were no differences in the clinical failure rate (3% vs. 7%, p = 0.30), 90-day patency rate, or procedure time between the MCT group and the traditional group. There was no symptomatic pulmonary embolism or other complication in the two groups. CONCLUSION: MCT is a low-cost, less invasive, and safe procedure for thrombosed aneurysmal AVF, and it achieves a higher technical success rate than traditional angioplasty.
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Cilostazol is an antiplatelet agent with vasodilating effects that functions by increasing the intracellular concentration of cyclic adenosine monophosphate. We have previously shown that cilostazol has favorable effects on angiogenesis. However, there is no study to evaluate the effects of cilostazol on adiponectin. We investigated the effects of cilostazol on angiogenesis in diabetes in vitro and in vivo through adiponectin/adiponectin receptors (adipoRs) and the sirtuin 1 (SIRT1)/AMP-activated protein kinase (AMPK) signaling pathway. Human umbilical vein endothelial cells (HUVECs) and human aortic smooth muscle cells (HASMCs) were cocultured under high glucose (HG) conditions. Adiponectin concentrations in the supernatants were significantly increased when HASMCs were treated with cilostazol but not significantly changed when only HUVECs were treated with cilostazol. Cilostazol treatment enhanced the expression of SIRT1 and upregulated the phosphorylation of AMPK in HG-treated HUVECs. By sequential knockdown of adipoRs, SIRT1, and AMPK, our data demonstrated that cilostazol prevented apoptosis and stimulated proliferation, chemotactic motility, and capillary-like tube formation in HG-treated HUVECs through the adipoRs/SIRT1/AMPK signaling pathway. The phosphorylation of downstream signaling molecules, including acetyl-CoA carboxylase (ACC) and endothelial nitric oxide synthase (eNOS), was downregulated when HUVECs were treated with a SIRT1 inhibitor. In streptozotocin-induced diabetic mice, cilostazol treatment could improve blood flow recovery 21-28 days after inducing hindlimb ischemia as well as increase the circulating of CD34+CD45dim cells 14-21 days after operation; moreover, these effects were significantly attenuated by the knockdown of adipoR1 but not adipoR2. The expression of SIRT1 and phosphorylation of AMPK/ACC and Akt/eNOS in ischemic muscles were significantly attenuated by the gene knockdown of adipoRs. Cilostazol improves HG-induced endothelial dysfunction in vascular endothelial cells and enhances angiogenesis in diabetic mice by upregulating the expression of adiponectin/adipoRs and its SIRT1/AMPK downstream signaling pathway.
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Diabetes Mellitus Experimental , Sirtuina 1 , Animales , Humanos , Ratones , Acetil-CoA Carboxilasa/metabolismo , Adiponectina/metabolismo , Proteínas Quinasas Activadas por AMP/metabolismo , Cilostazol/farmacología , Diabetes Mellitus Experimental/metabolismo , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Isquemia/metabolismo , Fosforilación , Receptores de Adiponectina/genética , Receptores de Adiponectina/metabolismo , Transducción de Señal , Sirtuina 1/genética , Sirtuina 1/metabolismo , Neovascularización PatológicaRESUMEN
Proprotein convertase subtilisin/kexin type 9 (PCSK9) plays a key role in cholesterol homeostasis. Cilostazol exerts favorable cellular and metabolic effects; however, the effect of cilostazol on the expression of PCSK9 has not been previously reported. Our study aimed to investigate the potential mechanisms of action of cilostazol on the expression of PCSK9 and lipid homeostasis. We evaluated the effects of cilostazol on the expression of PCSK9 in HepG2 cells and evaluated potential molecular mechanisms by measuring signaling molecules in the liver and serum lipid profiles in high-fat diet-induced obese mice and normal chow-fed mice. Cilostazol treatment significantly induced the messenger RNA and protein expression of PCSK9 in HepG2 cells and enhanced PCSK9 promoter activity. Chromatin immunoprecipitation assays confirmed that cilostazol treatment enhanced PCSK9 transcription by binding to peroxisome proliferator-activated receptor-γ (PPARγ) via the PPARγ DNA response element. PPARγ knockdown attenuated the stimulatory effect of cilostazol on PCSK9. In vitro, cilostazol treatment increased PCSK9 expression in vehicle-treated HepG2 cells but decreased PCSK9 expression in palmitic acid-treated HepG2 cells. In vivo, cilostazol treatment increased the serum levels of PCSK9 in normal mice but significantly reduced PCSK9 levels in obese mice. The expressions of PCSK9-relevant microRNAs also showed similar results. Clinical data showed that cilostazol treatment significantly reduced serum PCSK9 levels in patients with obesity. The obesity-dependent effects of cilostazol on PCSK9 expression observed from bench to bedside demonstrates the therapeutic potential of cilostazol in clinical settings.
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Proproteína Convertasa 9 , Proproteína Convertasas , Animales , Cilostazol/farmacología , Lípidos , Ratones , Ratones Obesos , Obesidad/tratamiento farmacológico , PPAR gamma/genética , PPAR gamma/metabolismo , Proproteína Convertasa 9/genética , Proproteína Convertasa 9/metabolismo , Proproteína Convertasas/genética , Receptores de LDL/genética , Serina Endopeptidasas/metabolismo , SubtilisinasRESUMEN
Previous studies found that cilostazol has a favorable effect on glucose and lipid homeostasis, endothelial function, atherosclerosis, and vasculo-angiogenesis. However, it is poorly understood whether these effects can translate into better clinical outcomes. This study investigated the outcome effect of cilostazol in patients with coronary artery disease (CAD) or at a high risk of cardiovascular (CV) disease. We conducted a randomized, double-blind, placebo-controlled trial involving 266 patients who received cilostazol, 200 mg/day (n = 134) or placebo (n = 132). Pre-specified clinical endpoints including composite major adverse cardiovascular events (MACE) (CV death, non-fatal myocardial infarct, non-fatal stroke, hospitalization for heart failure, or unplanned coronary revascularization), the composite major coronary event (MCE) and major adverse CV and cerebrovascular event (MACCE), were prospectively assessed. The mean duration of follow-up was 2.9 years. Relative to placebo, cilostazol treatment had a borderline effect on risk reduction of MACE (hazard ratio [HR], 0.67; 95% confidence interval (CI), 0.34-1.33), whereas the beneficial effect in favor of cilostazol was significant in patients with diabetes mellitus or a history of percutaneous coronary intervention (p for interaction, 0.02 and 0.06, respectively). Use of cilostazol, significantly reduced the risk of MCE (HR, 0.38; 95% CI, 0.17-0.86) and MACCE (HR, 0.47; 95% CI, 0.23-0.96). A significantly lower risk of angina pectoris (HR, 0.38; 95% CI, 0.17-0.86) was also observed in the cilostazol group. After multi-variable adjustment, cilostazol treatment independently predicted a lower risk of MCE. In conclusion, these results suggest cilostazol may have beneficial effects in patients with CAD or at a high risk of CV disease.
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BACKGROUND: Primary cardiac angiosarcoma is a rare primary cardiac malignancy. Biopsy of such vascular-rich tumours may result in serious complications. CASE SUMMARY: This is a case of a 43-year-old woman who presented with syncope. According to clinical history, she initially had massive pericardial effusion, with an uncertain aetiology. Multimodality imaging at our hospital revealed a cauliflower-like tumour in the right atrium. Coronary angiography results confirmed multiple feeding vessels from the right coronary artery to the tumour. Thoracoscopic biopsy resulted in a massive bleeding requiring haemostasis via thoracotomy. Histopathological examination of the specimen showed an angiosarcoma with atypical cells and spindle cells in a myxomatous background. Treatment with systemic targeted therapy and chemotherapy was initiated, and the patient is still under active treatment. DISCUSSION: Cardiac angiosarcomas most commonly arise from the right atrium and may be hard to detect with transthoracic echocardiography. Biopsy of primary cardiac angiosarcomas requires careful planning because they are highly vascularized. Currently, no guidelines regarding the treatment of such tumours exist, and a multidisciplinary treatment is needed.
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Thrombolytic therapy plays an important role in treating venous thromboembolic events in patients with unstable hemodynamics or compromised limb circulation. Standard catheter-directed thrombolysis requires a lower dosage of thrombolytic agents than systemic thrombolysis, thus lowering the risk of bleeding. Pharmacomechanical catheter- directed thrombolysis further decreases the dose of thrombolytic agents and duration of infusion. Percutaneous mechanical thrombolysis may potentially become an alternative for patients not suitable for thrombolytic agents. With an increasing number of devices and ongoing trials, endovascular therapy is a promising development that may improve both safety and efficacy in treating venous thromboembolic diseases.
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The new generation, i.e., second- and third-generation, drug-eluting stents (DESs) remain a risk of in-stent restenosis (ISR). We evaluated the power of a genetic risk score (GRS) model to identify high-risk populations for new generation DES ISR. We enrolled patients with coronary artery disease (CAD) treated with new generations DESs by a single-center cohort study in Taiwan and evaluated their genetic profile. After propensity score matching, there were 343 patients and 153 patients in the derivation and validation cohorts, respectively. Five selected single-nucleotide polymorphisms (SNPs), i.e., SNPs in CAMLG, GALNT2, C11orf84, THOC5, and SAMD11, were included to calculate the GRS for new generation DES ISR. In the derivation and the validation cohorts, patients with a GRS greater than or equal to 3 had significantly higher new generation DES ISR rates. We provide biological information for interventional cardiologists prior to percutaneous coronary intervention by specific five SNP-derived GRS.
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Left ventricular (LV) global peak systolic longitudinal strain (GLS) is a sensitive measurement for detecting subtle LV systolic dysfunction and a powerful prognostic predictor. However, the clinical implication of LV GLS in lymphoma patients receiving cancer therapy remains unknown. We prospectively enrolled 74 lymphoma patients (57.9 ± 17.0 years old, 57% male). We performed echocardiographic studies after the 3rd and 6th cycles and 1 year after chemotherapy and a cardiopulmonary exercise test upon completion of 3 cycles of anticancer therapy. Cancer therapy-related cardiac dysfunction (CTRCD) was defined as a ≥ 15% relative reduction in GLS value from baseline. The primary outcome was a composite of all-cause mortality and heart failure events. Thirty-six patients (49%) had CTRCD (LV GLS: baseline vs. after 3rd cycle of therapy: 20.1 ± 2.6 vs. 17.5 ± 2.3%, p < 0.001). CTRCD was detected after the 3rd cycle of anticancer therapy. CTRCD patients had impaired exercise capacity (minute oxygen consumption/kg, CTRCD vs. CTRCD (-): 13.9 ± 3.1 vs. 17.0 ± 3.9 ml/kg/min, p = 0.02). More primary outcome events occurred in the CTRCD group (hazard ratio 3.21; 95% confidence interval 1.04-9.97; p = 0.03). LV GLS could detect subtle but clinically significant cardiac dysfunction in lymphoma patients in the early stage of anticancer therapy. CTRCD may be associated with not only a reduced exercise capacity but also a worse prognosis.
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Antineoplásicos/uso terapéutico , Corazón/efectos de los fármacos , Linfoma/tratamiento farmacológico , Anciano , Antineoplásicos/administración & dosificación , Relación Dosis-Respuesta a Droga , Prueba de Esfuerzo , Femenino , Corazón/fisiopatología , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Función Ventricular Izquierda/efectos de los fármacosRESUMEN
Cardiovascular disease is the leading cause of deaths worldwide, claiming an estimated total of 17.9 million lives each year, of which one-third of the people are under the age of 70 years. Since adult cardiomyocytes fail to regenerate, the heart loses the ability to repair itself after an injury, making patients with heart disease suffer from poor prognosis. Pluripotent stem cells have the ability to differentiate into cardiomyocytes in vitro through a well-established process, which is a new advancement in cardiac regeneration therapy. However, pluripotent stem cell-derived cardiomyocytes have certain drawbacks, such as the risk of arrhythmia and immune incompatibility. Thus, amniotic fluid stem cells (AFSCs), a relatively novel source of stem cells, have been exploited for their ability of pluripotent differentiation. In addition, since AFSCs are weakly positive for the major histocompatibility class II molecules, they may have high immune tolerance. In summary, the possibility of development of cardiomyocytes from AFSCs, as well as their transplantation in host cells to produce mechanical contraction, has been discussed. Thus, this review article highlights the progress of AFSC therapy and its application in the treatment of heart diseases in recent years.
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Líquido Amniótico/metabolismo , Isquemia Miocárdica , Miocardio/metabolismo , Miocitos Cardíacos , Células Madre Pluripotentes/metabolismo , Regeneración , Anciano , Diferenciación Celular , Humanos , Isquemia Miocárdica/metabolismo , Isquemia Miocárdica/terapia , Miocitos Cardíacos/metabolismo , Miocitos Cardíacos/trasplanteRESUMEN
Despite enormous advances in the treatment of cardiovascular disease (CVD), heart disease remains the leading cause of mortality and morbidity worldwide. Thus, there is a need for novel CVD therapeutics. CVD appears to be a custom-made scenario for applying stem cell therapy. Although human pluripotent stem cells can differentiate into cardiomyocytes to regenerate injured heart tissue and restore post-myocardial infarction cardiac function, several obstacles need to be overcome before cell therapy can be applied in CVD patients. One of these major hurdles is the immunological barrier. Currently, long-term immunosuppressant treatment is necessary for allogenic stem cell or organ transplantation to prevent rejection. However, the long-term use of immunosuppressants may cause serious adverse events such as nephrotoxicity, severe infections and malignancy. Thus, overcoming this immunological hurdle is crucial for the clinical application of stem cell therapy in cardiac regeneration. This review summarizes the recent advances and challenges of immunogenicity in relation to stem cell therapy.
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Pulmonary embolism (PE) is a potential life-threatening condition and risk-adapted diagnostic and therapeutic management conveys a favorable outcome. For patients at high risk for early complications and mortality, prompt exclusion or confirmation of PE by imaging is the key step to initiate and facilitate reperfusion treatment. Among patients with hemodynamic instability, systemic thrombolysis improves survival, whereas surgical embolectomy or percutaneous intervention are alternatives in experienced hands in scenarios where systemic thrombolysis is not the best preferred thromboreduction measure. For patients with suspected PE who are not at high risk for early complications and mortality, the organized approach using a structured evaluation system to assess the pretest probability, the age-adjusted D-dimer cut-offs, the appropriate selection of imaging tools, and proper interpretation of imaging results is important when deciding the allocation of treatment strategies. Patients with PE requires anticoagulation treatment. In patients with cancer and thrombosis, low-molecular-weight heparin (LMWH) used to be the standard regimen. Recently, three factor Xa inhibitors collectively show that non-vitamin K oral anticoagulants (NOACs) are as effective as LMWH in four randomized clinical trials. Therefore, NOACs are suitable and preferred in most conditions. Finally, chronic thromboembolic pulmonary hypertension is the most disabling long-term complication of PE. Because of its low incidence, the extra caution should be given when managing patients with PE.
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With the advancement of computed tomography pulmonary angiography, differentiating between acute and chronic thrombus in pulmonary embolism has become more feasible. However, whether pulmonary embolism with chronic thrombus contributes to a higher mortality than pulmonary embolism with acute thrombus remains undetermined. Additionally, the clinical features of patients with chronic thrombus are largely unknown. Herein, we aimed to investigate the incidence and outcomes of patients with pulmonary embolism and chronic thrombus. This retrospective study included patients with pulmonary embolism from 2008 to 2016 at National Cheng Kung University Hospital. After excluding patients with tumor emboli or other etiologies and a lack of computed tomography images, we identified 205 patients with acute thrombus and 58 patients with chronic thrombus. Patients with chronic thrombus initially presented mainly with dyspnea, and the etiology was not related to recent surgery. Patients with chronic thrombus had a significantly higher incidence of elevated right ventricular systolic pressure detected by echocardiography and a higher incidence of subsequent events due to residual pulmonary embolism. Despite no differences in clinically recurrent pulmonary embolism, patients with chronic thrombus presented with a higher risk of all-cause and pulmonary embolism-related mortality than patients with acute thrombus. Chronic thrombus (hazard ratio: 2.03, p = 0.03), simplified pulmonary embolism severity index, anticoagulant use, and body mass index were the independent factors for all-cause mortality. Our findings suggest that using computed tomography pulmonary angiography for identifying patients with pulmonary embolism and chronic thrombus, which was associated with a higher risk of mortality, is pivotal for early intervention in addition to anticoagulant use.
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Mature mammalian hearts possess very limited regenerative potential. The irreversible cardiomyocyte loss after heart injury can lead to heart failure and death. Pluripotent stem cells (PSCs) can differentiate into cardiomyocytes for cardiac repair, but there are obstacles to their clinical application. Among these obstacles is their potential for post-transplant rejection. Although human amniotic fluid-derived stem cells (hAFSCs) are immune privileged, they cannot induce cardiac differentiation. Thus, we generated hAFSC-derived induced PSCs (hAFSC-iPSCs) and used a Wnt-modulating differentiation protocol for the cardiac differentiation of hAFSC-iPSCs. In vitro studies using flow cytometry, immunofluorescence staining, and patch-clamp electrophysiological study, were performed to identify the characteristics of hAFSC-iPSC-derived cardiomyocytes (hAFSC-iPSC-CMs). We injected hAFSC-iPSC-CMs intramuscularly into rat infarcted hearts to evaluate the therapeutic potential of hAFSC-iPSC-CM transplantation. At day 21 of differentiation, the hAFSC-iPSC-CMs expressed cardiac-specific marker (cardiac troponin T), presented cardiomyocyte-specific electrophysiological properties, and contracted spontaneously. Importantly, these hAFSC-iPSC-CMs demonstrated low major histocompatibility complex (MHC) class I antigen expression and the absence of MHC class II antigens, indicating their low immunogenicity. The intramyocardial transplantation of hAFSC-iPSC-CMs restored cardiac function, partially remuscularized the injured region, and reduced fibrosis in the rat infarcted hearts. Therefore, hAFSC-iPSCs are potential candidates for the repair of infarcted myocardium.
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Líquido Amniótico/citología , Diferenciación Celular , Células Madre Embrionarias/citología , Privilegio Inmunológico , Células Madre Pluripotentes Inducidas/citología , Desarrollo de Músculos , Miocitos Cardíacos/citología , Animales , Biomarcadores , Modelos Animales de Enfermedad , Fenómenos Electrofisiológicos , Humanos , Inmunohistoquímica , Células Madre Pluripotentes Inducidas/inmunología , Células Madre Pluripotentes Inducidas/metabolismo , Infarto del Miocardio/diagnóstico , Infarto del Miocardio/etiología , Infarto del Miocardio/metabolismo , Infarto del Miocardio/terapia , Miocitos Cardíacos/metabolismo , Fenotipo , Ratas , Regeneración , Trasplante de Células Madre/métodos , Resultado del Tratamiento , Función Ventricular IzquierdaRESUMEN
BACKGROUND: Platelets with high hemostatic activity play an important role in the pathophysiology of acute coronary syndrome (ACS), and mean platelet volume (MPV) has been proposed to be an indicator of platelet reactivity. We evaluated the predictive value of MPV and the responsive value of MPV with different antiplatelet agents in association with the clinical outcomes of ACS patients. METHODS: A total of 1094 patients with ACS and 472 patients without ACS were included. Blood samples were taken at hospital admission, at routine follow-up within one year, and beyond one year. The patients were divided into a "high MPV group" (> 9.0 fl, n = 305), "medium MPV group" (7.9-9.0 fl, n = 517), and "low MPV group" (< 7.9 fl, n = 272). The average follow-up time was 2.4 years, and the endpoints were major adverse cardiovascular events (MACEs) including all-cause mortality, time to recurrent ACS, target vessel re-intervention and stroke. RESULTS: MPV was significantly higher in the patients with ACS than in those without ACS (8.6 ± 1.1 vs. 8.4 ± 1.0 fl, p = 0.007). MPV decreased in the following year (8.38 ± 1.02 fl, p < 0.001) and also beyond one year (8.38 ± 0.94 fl, p < 0.001) after ACS events. The changes in MPV were not significantly different between the patients receiving either clopidogrel or ticagrelor. The high MPV group had more cardiovascular risk factors and more MACEs than the low MPV group (p = 0.017). CONCLUSIONS: A higher MPV in patients with ACS was associated with more cardiovascular risk factors and more cardiovascular events during clinical follow-up.
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Chronic thromboembolic pulmonary hypertension (CTEPH), a late complication of pulmonary embolism (PE), is associated with high mortality. However, whether the right ventricular (RV) echocardiographic parameters can predict - in the short- and long-term - the development of CTEPH and mortality after PE remains unknown. Herein, we aim to investigate the incidence of CTEPH after acute PE and to evaluate the risk factors of CTEPH. In this retrospective cohort, patients with PE were followed for 10 years for the onset of CTEPH. The screening was initially conducted through echocardiography and confirmed by right heart catheterization. Also, transient and permanent risk factors were identified. Among 358 patients with PE, 8 patients (4%) were subsequently diagnosed with CTEPH at a median time of 36 months and 47 died during the follow-up period. Notably, both short- and long-term RV dilatation, hypertrophy, and increased pulmonary pressure increased the incidence of CTEPH. However, RV echocardiographic parameters failed to differentiate survivors from non-survivors. Instead, malignancy, respiratory, or chronic heart failure was strongly associated with post PE mortality in the multivariable analysis. According to our findings, post PE screening of CTEPH may facilitate early diagnosis and intervention for patients at high risk of developing CTEPH. Also, RV echocardiographic parameters are associated with subsequent CTEPH, but mortality is mainly dependent on underlying comorbidities.