Uso de aspirina en prevención primaria cardiovascular: es tiempo de cambiar el paradigma / Aspirin use for primary cardiovascular prevention: time for a paradigm shift

La Aspirina es una droga ampliamente utilizada con un protagonismo indiscutido en el escenario de la prevención secundaria. Sin embargo, el rol de este medicamento en prevención primaria es aún motivo de discusión. Los primeros ensayos que evaluaron la Aspirina en prevención primaria sugerían reducciones en el infarto agudo al miocardio y el accidente cerebrovascular -aunque no en la mortalidad- con un riesgo no despreciable de hemorragia mayor. Esto llevó a diversas sociedades científicas a recomendar su prescripción sólo en aquellos individuos con alto riesgo de eventos cardiovasculares. Desde el año 2018 en adelante, surgen diversos ensayos aleatorizados que han cuestionado estas indicaciones, mostrando beneficios clínicos muy discretos o ausentes. El objetivo de esta revisión es realizar un análisis histórico de la evidencia sobre el rol de la Aspirina en prevención primaria y resumir las recomendaciones actuales en este escenario.

Aspirin is widely used with a clear role in secondary prevention of cardiovascular diseases. However, its benefit in primary prevention is still a matter of discussion. The first trials evaluating Aspirin for primary prevention suggested reductions in acute myocardial infarction and stroke (although not in mortality) but with a non-negligible risk of major bleeding. This led to aspirin being recommended by various scientific societies, albeit limited to individuals at high risk of cardiovascular events. Since 2018 various randomized trials in primary prevention showed minimal or no beneficial effects of aspirin thus questioning its indication for this purpose. The aim of this review is to make an historical analysis of the evidence for the role of Aspirin in primary prevention and suggest modified recommendations for these subjects.

Changes in process and outcome for ST elevation myocardial infarction in central China from 2011 to 2018 / 中华医学杂志(英文版)

BACKGROUND@#Limited data are available on the changes in the quality of care for ST elevation myocardial infarction (STEMI) during China's health system reform from 2009 to 2020. This study aimed to assess the changes in care processes and outcome for STEMI patients in Henan province of central China between 2011 and 2018.@*METHODS@#We compared the data from the Henan STEMI survey conducted in 2011-2012 ( n = 1548, a cross-sectional study) and the Henan STEMI registry in 2016-2018 ( n = 4748, a multicenter, prospective observational study). Changes in care processes and in-hospital mortality were determined. Process of care measures included reperfusion therapies, aspirin, P2Y12 antagonists, β-blockers, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, and statins. Therapy use was analyzed among patients who were considered ideal candidates for treatment.@*RESULTS@#STEMI patients in 2016-2018 were younger (median age: 63.1 vs . 63.8 years) with a lower proportion of women (24.4% [1156/4748] vs . 28.2% [437/1548]) than in 2011-2012. The composite use rate for guideline-recommended treatments increased significantly from 2011 to 2018 (60.9% [5424/8901] vs . 82.7% [22,439/27,129], P <0.001). The proportion of patients treated by reperfusion within 12 h increased from 44.1% (546/1237) to 78.4% (2698/3440) ( P <0.001) with a prolonged median onset-to-first medical contact time (from 144 min to 210 min, P <0.001). The use of antiplatelet agents, statins, and β-blockers increased significantly. The risk of in-hospital mortality significantly decreased over time (6.1% [95/1548] vs . 4.2% [198/4748], odds ratio [OR]: 0.67, 95% confidence interval [CI]: 0.50-0.88, P = 0.005) after adjustment.@*CONCLUSIONS@#Gradual implementation of the guideline-recommended treatments in STEMI patients from 2011 to 2018 has been associated with decreased in-hospital mortality. However, gaps persist between clinical practice and guideline recommendation. Public awareness, reperfusion strategies, and construction of chest pain centers need to be further underscored in central China.

Manejo de la anticoagulación y tromboprofilaxis en paciente con patología neuroquirúrgica / Consideration of anticoagulation and thromboprophylaxis in neuroanesthesia

Anesthesiologists are being increasingly confronted to manage anticoagulated patients or those who are under the effect of thromboprophylaxis, they must take care of all aspects needed to ensure a secure perioperative outcome in neurosurgical pathologies.

Cada vez es más frecuente que los anestesiólogos nos veamos enfrentados a pacientes que ingresan a pabellón por diversas patologías neuroquirúrgicas mientras se encuentran en tratamiento con terapia anticoagulante y/o tromboprofilaxis.

Current use of oral anticoagulation therapy and influencing factors among coronary artery disease patients with nonvalvular atrial fibrillation in China / 中华心血管病杂志

Objective: To investigate current use of oral anticoagulant (OAC) therapy and influencing factors among coronary artery disease (CAD) patients with nonvalvular atrial fibrillation (NVAF) in China. Methods: Results of this study derived from "China Atrial Fibrillation Registry Study", the study prospectively enrolled atrial fibrillation (AF) patients from 31 hospitals, and patients with valvular AF or treated with catheter ablation were excluded. Baseline data such as age, sex and type of atrial fibrillation were collected, and drug history, history of concomitant diseases, laboratory results and echocardiography results were recorded. CHA2DS2-VASc score and HAS-BLED score were calculated. The patients were followed up at the 3rd and 6th months after enrollment and every 6 months thereafter. Patients were divided according to whether they had coronary artery disease and whether they took OAC. Results: 11 067 NVAF patients fulfilling guideline criteria for OAC treatment were included in this study, including 1 837 patients with CAD. 95.4% of NVAF patients with CAD had CHA2DS2-VASc score≥2, and 59.7% of patients had HAS-BLED≥3, which was significantly higher than NVAF patients without CAD (P<0.001). Only 34.6% of NVAF patients with CAD were treated with OAC at enrollment. The proportion of HAS-BLED≥3 in the OAC group was significantly lower than in the no-OAC group (36.7% vs. 71.8%, P<0.001). After adjustment with multivariable logistic regression analysis, thromboembolism(OR=2.48,95%CI 1.50-4.10,P<0.001), left atrial diameter≥40 mm(OR=1.89,95%CI 1.23-2.91,P=0.004), stain use (OR=1.83,95%CI 1.01-3.03, P=0.020) and β blocker use (OR=1.74,95%CI 1.13-2.68,P=0.012)were influence factors of OAC treatment. However, the influence factors of no-OAC use were female(OR=0.54,95%CI 0.34-0.86,P=0.001), HAS-BLED≥3 (OR=0.33,95%CI 0.19-0.57,P<0.001), and antiplatelet drug(OR=0.04,95%CI 0.03-0.07,P<0.001). Conclusion: The rate of OAC treatment in NVAF patients with CAD is still low and needs to be further improved. The training and assessment of medical personnel should be strengthened to improve the utilization rate of OAC in these patients.

Anticoagulation status and adherence in patients with atrial fibrillation hospitalized for ACS and the impact on 1-year prognosis: a multicenter cohort study / 中华心血管病杂志

Objective: For patients with atrial fibrillation (AF) complicated with acute coronary syndrome (ACS), both anticoagulant and antiplatelet therapy should be applied, but the use of anticoagulation therapy is still poor in these patients in China. The purpose of this study was to explore the status and adherence of antithrombotic therapy in AF patients with ACS and the impact on 1 year clinical outcomes. Methods: Patients with AF hospitalized for ACS were retrospectively included from 6 tertiary hospitals in China between July 2015 and December 2020. According to the use of anticoagulant drugs at discharge, patients were divided into two groups: anticoagulant treatment group and non-anticoagulant treatment group. Logistic regression model was used to analyze the main factors influencing the use of anticoagulant drugs in patients with atrial fibrillation complicated with ACS. Major adverse cardiac events (MACEs) were defined as all-cause death, non-fatal myocardial infarction or coronary revascularization, and ischemic stroke and Bleeding Academic Research Consortium (BARC) 3 bleeding events were also collected at 1 year after discharge. After propensity score matching, Cox proportional hazards models and Kaplan-Meier analysis were used to evaluate the effect of anticoagulant treatment and non-anticoagulant treatment on 1-year prognosis. The patients were divided into different groups according to whether anticoagulation was performed at discharge and follow-up, and the sensitivity of the results was analyzed. Results: A total of 664 patients were enrolled, and 273 (41.1%) were treated with anticoagulant therapy, of whom 84 (30.8%) received triple antithrombotic therapy, 91 (33.3%) received double antithrombotic therapy (single antiplatelet combined with anticoagulant), and 98 (35.9%) received single anticoagulant therapy. Three hundred and ninety-one (58.9%) patients were treated with antiplatelet therapy, including 253 (64.7%) with dual antiplatelet therapy and 138 (35.3%) with single antiplatelet therapy. After 1∶1 propensity score matching between the anticoagulant group and the non-anticoagulant group, a total of 218 pairs were matched. Multivariate logistic regression analysis showed that history of diabetes, HAS-BLED score≥3, and percutaneous coronary intervention were predictors of the absence of anticoagulant therapy, while history of ischemic stroke and persistent atrial fibrillation were predictors of anticoagulant therapy. At 1-year follow-up, 218 patients (79.9%) in the anticoagulant group continued to receive anticoagulant therapy, and 333 patients (85.2%) in the antiplatelet group continued to receive antiplatelet therapy. At 1-year follow-up, 36 MACEs events (13.2%) occurred in the anticoagulant group, and 81 MACEs events (20.7%) in the non-anticoagulant group. HR values and confidence intervals were calculated by Cox proportional risk model. Patients in the non-anticoagulant group faced a higher risk of MACEs (HR=1.802, 95%CI 1.112-2.921, P=0.017), and the risk of bleeding events was similar between the two group (HR=0.825,95%CI 0.397-1.715, P=0.607). Conclusions: History of diabetes, HAS-BLED score≥3, and percutaneous coronary intervention are independent factors for the absence of anticoagulant therapy in patients with AF complicated with ACS. The incidence of MACEs, death and myocardial infarction is lower in the anticoagulant group, and the incidence of bleeding events is similar between the two groups. The risk of bleeding and ischemia/thrombosis should be dynamically assessed during follow-up and antithrombotic regiments should be adjusted accordingly.

Application of Rotarex catheter system in femoropopliteal artery stenosis accompanied with thrombosis / 北京大学学报(医学版)

OBJECTIVE@#To evaluate the effectiveness and safety of Rotarex catheter system in treating femoropopliteal artery stenosis accompanied with thrombosis.@*METHODS@#From Jun. 2017 to Dec. 2019, the clinical data of 32 femoropopliteal artery stenosis accompanied with thrombosis cases treated with Rotarex catheter system were retrospectively analyzed. There were 23 males and 9 females aged from 50 to 89 years and the mean age was (70.7±10.3) years. Six cases had acute course of disease (≤2 weeks), 17 cases had subacute course of disease (>2 weeks, ≤3 months), and 9 cases had chronic course of disease (>3 months). Mean lesion length was (23.4±13.7) cm, mean occlusion length was (19.9±13.3) cm, and in-stent occlusion 7 cases. The superficial femoral artery (SFA) was involved in 13 cases, the popliteal artery (PA) was involved in 8 cases, and both SFA and PA were involved in the other 11 cases. All the cases were treated with Rotarex catheter system. When necessary, suction with large lumen catheter was enabled. Residual stenosis was treated with percutaneous transluminal angioplasty (PTA). Drug-coated balloon (DCB) was only used in patients with financial status, and stent was used only when it was necessary. Heparin was used for 24 h after procedures, and after that, antiplatelet agents were used. Doppler ultrasonography was taken during the followed-up.@*RESULTS@#Technical success was 100%, and mean procedure time was (107.4±21.5) min. 8F (1F≈0.33 mm) and 6F Rotarex catheter were used in 27 and 5 cases respectively. In 27 cases, forward flow was obtained immediately after debulking with Rotarex catheter, and in the other 5 cases, suction with large lumen catheters were used. PTA was used in all 32 cases. DCB were used in 8 cases, of which 4 were used in in-stent stenosis. Twelve cases were implanted stents. There were no perioperative deaths. The only one procedure related complication was distal embolism. We took out the thrombus with guiding catheter. In all cases, mean hospital stay were (4.6±1.5) d. The ankle brachial index increased from 0.32±0.15 to 0.86±0.10 after treatment (t=-16.847, P < 0.001). The Rutherford stages decreased significantly (Z=-4.518, P < 0.001). All the patients were followed up for 6.0-36.0 months, and the median time was 16.0 months. 2 cases stopped antiplatelet agents, which resulted in acute thrombosis. Another percutaneous mechanical thrombectomy and PTA were taken in one of them. Two cases died of cardiovascular disease during the follow-up, and no amputation was observed. Target lesion restenosis occurred in 7 cases during the follow-up, and target lesion revascularization (TLR) was taken in two of them.@*CONCLUSION@#In treating femoropopliteal artery stenosis accompanied with thrombosis, Rotarex catheter can remove thrombus effectively, and that can expose underlying lesions and reduce stent use and complications rates. It is a safe and effective method.

Notch signaling pathway inhibitor DAPT improves alcohol-induced neuronal differentiation impairment in zebrafish / 南方医科大学学报

OBJECTIVE@#To explore the role of the Notch signaling pathway in regulating neuronal differentiation and sensorimotor ability in a zebrafish model of fetal alcohol spectrum disorder.@*METHODS@#Zebrafish embryos treated with DMSO or 50 μmol/L DAPT (a Notch signaling pathway inhibitor) were examined for mortality rate, hatching rate, malformation rate, and body length at 15 days post fertilization (dpf). The mRNA expression levels of sox2, neurogenin1 and huc in the treated zebrafish embryos were detected using in situ hybridization and qRT-PCR, and their behavioral responses to strong light and vibration stimulation were observed. The zebrafish embryos were then exposed to DMSO, 1.5% ethanol, DAPT, or both ethanol and DAPT, and the changes in mRNA expression levels of sox2, neurogenin1, huc, and the Notch signaling pathway genes as well as behavioral responses were evaluated.@*RESULTS@#Exposure to 50 μmol/L DAPT significantly increased the mortality rate of 1 dpf zebrafish embryos (P < 0.01), decreased the hatching rate of 2 dpf embryos (P < 0.01), increased the malformation rate of 3 dpf embryos (P < 0.001), and reduced the body length of 15 dpf embryos (P < 0.05). DAPT treatment significantly downregulated sox2 mRNA expression (P < 0.01) and increased neurogenin1 (P < 0.05) and huc (P < 0.01) mRNA expressions in zebrafish embryos. The zebrafish with DAPT treatment exhibited significantly shortened movement distance (P < 0.001) and lowered movement speed (P < 0.05) in response to all the stimulation conditions. Compared with treatment with 1.5% ethanol alone, which obviously upregulated notch1a, her8a and NICD mRNA expressions in zebrafish embryos (P < 0.05), the combined treatment with ethanol and DAPT significantly increased neurogenin1 and huc mRNA expression, decreased sox2 mRNA expression (P < 0.01), and increased the moving distance and moving speed of zebrafish embryos in response to strong light stimulation (P < 0.05).@*CONCLUSION@#Ethanol exposure causes upregulation of the Notch signaling pathway and impairs neuronal differentiation and sensorimotor ability of zebrafish embryos, and these detrimental effects can be lessened by inhibiting the Notch signaling pathway.

Microfluidic Chip and Flow Cytometry for Examination of the Antiplatelet Effect of Ticagrelor / 中国医学科学院学报

Objective To examine the antiplatelet effect of ticagrelor by microfluidic chip and flow cytometry under shear stress in vitro. Methods Microfluidic chip was used to examine the effect of ticagrelor on platelet aggregation at the shear rates of 300/s and 1500/s.We adopted the surface coverage of platelet aggregation to calculate the half inhibition rate of ticagrelor.The inhibitory effect of ticagrelor on ADP-induced platelet aggregation was verified by optical turbidimetry.Microfluidic chip was used to construct an in vitro vascular stenosis model,with which the platelet reactivity under high shear rate was determined.Furthermore,the effect of ticagrelor on the expression of fibrinogen receptor (PAC-1) and P-selectin (CD62P) on platelet membrane activated by high shear rate was analyzed by flow cytometry. Results At the shear rates of 300/s and 1500/s,ticagrelor inhibited platelet aggregation in a concentration-dependent manner,and the inhibition at 300/s was stronger than that at 1500/s (both P<0.001).Ticagrelor at a concentration ≥4 μmol/L almost completely inhibited platelet aggregation.The inhibition of ADP-induced platelet aggregation by ticagrelor was similar to the results under flow conditions and also in a concentration-dependent manner.Ticagrelor inhibited the expression of PAC-1 and CD62P. Conclusion We employed microfluidic chip to analyze platelet aggregation and flow cytometry to detect platelet activation,which can reveal the responses of different patients to ticagrelor.

Study on Platelet Adhesion and Aggregation Induced by Gradient Shear Stress Using Microfluidic Chip Technology / 中国实验血液学杂志

OBJECTIVE@#To study the effect of gradient shear stress on platelet aggregation by microfluidic chip Technology.@*METHODS@#Microfluidic chip was used to simulate 80% fixed stenotic microchannel, and the hydrodynamic behavior of the stenotic microchannel model was analyzed by the finite element analysis module of sollidwork software. Microfluidic chip was used to analyze the adhesion and aggregation behavior of platelets in patients with different diseases, and flow cytometry was used to detect expression of the platelet activation marker CD62p. Aspirin, Tirofiban and protocatechuic acid were used to treat the blood, and the adhesion and aggregation of platelets were observed by fluorescence microscope.@*RESULTS@#The gradient fluid shear rate produced by the stenosis model of microfluidic chip could induce platelet aggregation, and the degree of platelet adhesion and aggregation increased with the increase of shear rate within a certain range of shear rate. The effect of platelet aggregation in patients with arterial thrombotic diseases were significantly higher than normal group (P<0.05), and the effect of platelet aggregation in patients with myelodysplastic disease was lower than normal group (P<0.05).@*CONCLUSION@#The microfluidic chip analysis technology can accurately analyze and evaluate the platelet adhesion and aggregation effects of various thrombotic diseases unde the environment of the shear rate, and is helpful for auxiliary diagnosis of clinical thrombotic diseases.

Mechanism of Notch3 signaling pathway regulating the differentiation of aortic dissection vascular stem cells into smooth muscle cells / 中华危重病急救医学

OBJECTIVE@#To explore whether the differentiation of vascular stem cells (VSC) into smooth muscle cells (SMC) in aortic dissection (AD) is dysregulated, and to verify the role of Notch3 pathway in this process.@*METHODS@#Aortic tissues were obtained from AD patients undergoing aortic vascular replacement and heart transplant donors at Department of Cardiovascular Surgery, Guangdong Provincial People's Hospital Affiliated to Southern Medical University. VSC were isolated by enzymatic digestion and c-kit immunomagnetic beads. The cells were divided into normal donor-derived VSC group (Ctrl-VSC group) and AD-derived VSC group (AD-VSC group). The presence of VSC in the aortic adventitia was detected by immunohistochemical staining, and VSC was identified by stem cell function identification kit. The differentiation model of VSC into SMC established in vitro was induced by transforming growth factor-β1 (10 μg/L) for 7 days. They were divided into normal donor VSC-SMC group (Ctrl-VSC-SMC group), AD VSC-SMC group (AD-VSC-SMC group) and AD VSC-SMC+Notch3 inhibitor DAPT group (AD-VSC-SMC+DAPT group,DAPT 20 μmol/L was added during differentiation induction). The expression of contractile marker Calponin 1 (CNN1) in SMC derived from aortic media and VSC were detected by immunofluorescence staining. The protein expressions of contractile markers α-smooth muscle actin (α-SMA), CNN1 as well as Notch3 intracellular domain (NICD3) in SMC derived from aortic media and VSC were detected by Western blotting.@*RESULTS@#Immunohistochemical staining showed there was a population of c-kit-positive VSC in the adventitia of aortic vessels, and VSC from both normal donors and AD patients had the ability to differentiate into adipocytes and chondrocytes. Compared with normal donor vascular tissue, the expressions of SMC markers α-SMA and CNN1 of tunica media contraction in AD were down-regulated (α-SMA/β-actin: 0.40±0.12 vs. 1.00±0.11, CNN1/β-actin: 0.78±0.07 vs. 1.00±0.14, both P < 0.05), while the protein expression of NICD3 was up-regulated (NICD3/GAPDH: 2.22±0.57 vs. 1.00±0.15, P < 0.05). Compared with Ctrl-VSC-SMC group, the expressions of contractile SMC markers α-SMA and CNN1 were down-regulated in AD-VSC-SMC group (α-SMA/β-actin: 0.35±0.13 vs. 1.00±0.20, CNN1/β-actin: 0.78±0.06 vs. 1.00±0.07, both P < 0.05), the protein expression of NICD3 was up-regulated (NICD3/GAPDH: 22.32±1.22 vs. 1.00±0.06, P < 0.01). Compared with AD-VSC-SMC group, the expressions of contractile SMC markers α-SMA, CNN1 were up-regulated in AD-VSC-SMC+DAPT group (α-SMA/β-actin: 1.70±0.07 vs. 1.00±0.15, CNN1/β-actin: 1.62±0.03 vs. 1.00±0.02, both P < 0.05).@*CONCLUSIONS@#Dysregulation of VSC differentiation into SMC occurs in AD, while inhibition of Notch3 pathway activation can restore the expression of contractile proteins in VSC-derived SMC in AD.

Sangramiento posextracción dentaria y medidas para su control en pacientes tratados con antiagregantes plaquetarios / Bleeding after tooth extraction and measures for its control in patients treated with antiplatelet agents

Introducción: El desarrollo de las ciencias médicas trae consigo un incremento en la expectativa de vida, junto a la detección temprana de un gran número de enfermedades crónicas como las cerebrovasculares y cardiovasculares, que son tratadas rutinariamente con medicamentos antiagregantes plaquetarios. El conocimiento del manejo de estos pacientes ante los procedimientos quirúrgicos estomatológicos constituye un reto en la práctica diaria profesional. Objetivo: Determinar el nivel de sangramiento posextracción dentaria en pacientes con enfermedad cardiovascular y cerebrovascular, según el tipo de antiagregantes plaquetarios y grupo dentario, así como la frecuencia de utilización de las medidas para su control. Métodos: Se efectuó un estudio observacional, descriptivo, longitudinal y prospectivo con un universo de 136 pacientes de más de 20 años, remitidos por su cardiólogo y que necesitaban realizarse extracciones dentarias sin modificar su tratamiento con antiagregantes plaquetarios. Las variables estudiadas fueron la enfermedad sistémica, el tipo de antiagregante plaquetario, el nivel de sangramiento, grupo dentario intervenido y método hemostático utilizado. Resultados: La mitad de los pacientes estudiados no presentó sangramiento posextracción dentaria. En los pacientes tratados con aspirina o clopidogrel predominaron los sujetos sin sangramiento para un 84,3 por ciento y 62,5 por ciento, respectivamente. En los de doble antiagregación prevaleció el sangramiento moderado con un 46,3 por ciento. Los grupos dentarios incisivo, canino y premolar no presentaron episodios de sangramiento para un 64,1 por ciento, 51,6 por ciento y 53,3por ciento, respectivamente. El método hemostático más utilizado fue la compresión de las corticales y termoterapia fría (47,8 por ciento). Conclusiones: La mitad de los pacientes con enfermedades cardiovasculares y cerebrovasculares no presentaron sangramiento posextracción dentaria(AU)

Introduction: The development of medical sciences brings with it an increase in life expectancy, together with the early detection of a large number of chronic diseases such as cerebrovascular and cardiovascular diseases, which are routinely treated with antiplatelet aggregation drugs. Knowledge on the treatment of these patients before stomatological surgical procedures constitutes a challenge in daily professional practice. Objective: To determine the level of bleeding after tooth extraction in patients with cardiovascular and cerebrovascular disease, according to the type of antiplatelet agents and dental group, as well as the frequency of use of measures for their control. Methods: An observational, descriptive, longitudinal and prospective study was carried out with a universe of 136 patients over 20 years of age, referred by their cardiologist, who needed dental extractions without modifying their treatment with antiplatelet agents. The variables studied were systemic disease, type of antiplatelet agent, level of bleeding, dental group treated and hemostatic method used. Results: Half of the patients studied did not present bleeding after tooth extraction. In patients treated with aspirin or clopidogrel, 84.3 percent and 62.5por ciento, respectively, had no bleeding. In those with double antiplatelet therapy, modera te bleeding prevailed with 46.3 The incisor, canine and premolar tooth groups did not present bleeding episodes (64.1 percent, 51.6and 53.3 percent respectively). The most commonly used hemostatic method was cortical compression and cold thermotherapy (47.8%). Conclusions: Half of the patients with cardiovascular and cerebrovascular diseases did not present bleeding after tooth extraction(AU)

Drogas antiagregantes plaquetárias e anticoagulantes em pacientes que se submeterão à cirurgia oral: conduta / Antiagregant platelet and anticoagulant drugs in patients who will submit oral surgery: conduct

Objetivo: Como a frequência de pacientes em uso de anticoagulantes e antiagragantes plaquetários nos consultórios odontológicos é crescente, este trabalho objetivou avaliar através de Revisão de Literatura, qual o melhor manejo desses medicamentos na prática odontológica perioperatória. Metodologia: Trata-se de uma revisão integrativa da literatura, utilizadas as bases de dados Scielo e PubMed. Foram escolhidos os seguintes descritores disponíveis na BVs e PubMed em inglês "Platelet Aggregation Inhibitors", "Oral Surgical Procedures" e "Antigoagulants" no período de 2016 a 2021. Também foram consultados livros e sites de diretrizes do Governo. Foram escolhidos 20 artigos para elaboração da pesquisa. Resultados: doenças cardiovasculares e outras condições clínicas pró-coagulantes tem prevalência crescente e são conhecidos fatores de risco para a ocorrência de fenômenos tromboembólicos graves. A terapia antitrombótica tem papel definido nesses casos. No perioperatorio de cirurgias orais, a decisão por suspender ou manter a terapia deve ser individualizada e pode ser orientada por guidelines. Conclusão: procedimentos orais de baixo risco de sangramento podem ser conduzidos sem a descontinuação da terapia antitrombótica. Cirurgias de moderado a alto risco frequentemente requerem suspensão temporária das medicações para fins de minimizar os riscos de complicações hemorrágicas... (AU)

Objective: As the frequency of patients using anticoagulants and antiplatelet agents in dental offices is increasing, this study aimed to evaluate, through a Literature Review, which is the best management of these medications in dental perioperative practice. Methodology: This is an integrative literature review, being used Scielo and PubMed databases. The following descriptors available in BVs and PubMed "Platelet aggregation inhibitors", "Oral Surgical Procedures" and "Antigoagulants" were used, from 2016 to 2021. In addition, the search was also performed in guideline books and Government websites. Twenty articles were chosen for research elaboration. Results: established cardiovascular disease and other procoagulant clinical conditions have an increasing prevalence, especially among the elderly, and are known risk factors for the occurrence of severe thromboembolic phenomena. Antithrombotic therapy has defined role in these cases. In the perioperative period of oral surgery, the decision to suspend or maintain therapy must be individualized and may be guided by guidelines. Age appears as a clinical criterion in the main ones used. Conclusion: oral procedures with low risk of bleeding can be carried out without discontinuing antithrombotic therapy. Moderate to high-risk surgeries usually require its temporary suspension in order to minimize the risk of bleeding complications... (AU)

Antiagregación plaquetaria: stents, isquemia y sangrado ¿Qué sabemos al respecto? / Platelet antiaggregation: stents, ischemia and bleeding What do we know about it?

Antiplatelet therapy and percutaneous coronary intervention are two of the most important interventions in the management of coronary artery disease. In the last 20 years there has been groundbreaking advances in the pharmacotherapy and stent technology. Bleeding is the most feared complication of antiplatelet therapy, mainly due to the increase in major adverse cardiovascular events besides the bleeding itself. Different clinical decision tools have developed with the aim to define which patients have a high ischemic or bleeding risk, thus individualizing treatment.

Cuidados que o cirurgião-dentista deve tomar no momento de tratar cirurgicamente um paciente em uso de anticoagulantes ou antiagregantes plaquetários / Care that the dental surgeon must take when treating surgically a patient using anticoagulants or antiplatelet agents

Os anticoagulantes e antiagregantes plaquetários são medicamentos utilizados por uma grande parcela da população mundial. Eles são utilizados para prevenir que pacientes de risco desenvolvam doenças cardiovasculares, como o infarto agudo do miocárdio (IAM) ou o acidente vascular cerebral (AVC). Por serem muito utilizados, constantemente o cirurgião-dentista poderá se deparar em sua rotina clínica, com pacientes usuários de anticoagulantes ou antiagregantes. Neste caso, o profissional precisará estar ciente das normas mais atuais de manejo com cada um dos tipos de medicamentos, para que o tratamento seja realizado com sucesso. No presente trabalho, é proposto um Protocolo Operacional Padrão (POP), que pode ser seguido no momento de realizar cirurgias orais em pacientes em uso de Varfarina, Ácido Acetil Salicílico, Heparina de Baixo Peso Molecular, Heparina Não Fracionada, Rivaroxabana e Clopidogrel.

Anticoagulants and antiplatelet agents are drugs used by a large portion of the world population. They are used to prevent at-risk patients from developing cardiovascular diseases, such as acute myocardial infarction (AMI) or stroke (stroke). Because they are widely used, the dental surgeon may constantly encounter patients using anticoagulants or anti-aggregating agents in their clinical routine. In this case, the professional will need to be aware of the most current management standards with each type of medication, so that the treatment is carried out successfully. In the present work, a Standard Operational Protocol (POP) is proposed, which can be followed when performing oral surgeries on patients using Warfarin, Acetyl Salicylic Acid, Low Molecular Weight Heparin, Unfractionated Heparin, Rivaroxaban and Clopidogrel.

Disnea secundaria a ticagrelor posterior a arteriografía coronaria. Reporte de caso / Dyspnea secondary to ticagrelor posterior to coronary arteriography. Case report

Resumen Los antiagregantes plaquetarios son medicamentos ampliamente utilizados para la prevención y tratamiento de patologías aterotrombóticas, como lo es el síndrome coronario agudo. A pesar de tener un efecto benéfico, no están exentos de ocasionar múltiples alteraciones a nivel sistémico, como lo es la disnea en pacientes sometidos a manejo con ticagrelor. Se expone el caso de un paciente de 66 años con antecedente de cardiopatía isquémico-hipertensiva, tabaquismo pesado y alergia al ácido acetilsalicílico (ASA), con requerimiento de 2 arteriografías coronarias, quien presenta disnea en reposo en menos de 24 horas posterior al inicio de manejo antiagregante tromboprofiláctico con ticagrelor, que resuelve de forma satisfactoria tras la suspensión del medicamento. Al ser un efecto secundario relativamente frecuente en el marco del uso del ticagrelor, se hace relevante revisar los hallazgos en la literatura actual sobre la aparición de disnea en pacientes tratados con dicho fármaco, para así tener en cuenta posibles recomendaciones acerca del manejo de la disnea asociada a ticagrelor, basadas en el conocimiento actual. MÉD.UIS.2022;35(1): 9-15.

Abstract Antiplatelet agents are widely used drugs for the prevention and treatment of atherothrombotic pathologies such as acute coronary syndrome, however, despite having a beneficial effect, they're not exempt from causing multiple systemic alterations, such as dyspnea in patients undergoing management with ticagrelor. We will now present the case of a 66-year-old patient with a history of hypertensive ischemic heart disease requiring 2 cardiac catheterizations, heavy smoking and allergic to Acetyl Salicylic Acid (ASA) who presented dyspnea at rest in less than 24 hours after the start of thromboprophylaxis management with ticagrelor, that resolves satisfactorily after discontinuation of the drug. Because it is a frequent side effect in the framework of the use of ticagrelor, it's relevant to review the current literature on the appearance of dyspnea in patients treated with ticagrelor, to highlight recommendations for the management of dyspnea associated with ticagrelor based on current knowledge. MÉD.UIS.2022;35(1): 9-15.

Síndrome de vena cava superior: una serie de casos consecutivos en pacientes internados en un hospital terciario universitario / Superior vena cava syndrome: a consecutive case series of in-hospital patients in a tertiary teaching hospital

Introducción: el síndrome de vena cava superior resulta de la obstrucción del flujo sanguíneo a través de este vaso. Casi la totalidad de los casos en la actualidad se asocian con tumores malignos. Existen controversias acerca del manejo apropiado de este cuadro. Actualmente, las terapias endovasculares son consideradas de elección. Materiales y métodos: se recolectaron y describieron, a partir de datos de la historia clínica electrónica, los casos de pacientes mayores de 18 años internados ­de forma consecutiva, que desarrollaron el síndrome­ en el Hospital Italiano de Buenos Aires en 2021. Se constataron las características basales, los tratamientos recibidos y los desenlaces clínicos intrahospitaliarios de cada uno de ellos. Resultados: un total de cinco pacientes fueron incluidos en el presente estudio y seguidos durante su instancia intrahospitalaria. Todos los casos descriptos fueron secundarios a enfermedades oncológicas. La mayoría de los pacientes presentaron un cuadro de moderada gravedad según las escalas utilizadas. En cuatro de cinco pacientes se optó por terapias endovasculares y dos de ellos fallecieron durante la internación. Discusión: existen controversias respecto del tratamiento óptimo del síndrome de vena cava superior, y heterogeneidad en la práctica clínica. Los estudios futuros deberían centrarse en identificar a aquellos pacientes que más probablemente se beneficien de las estrategias terapéuticas endovasculares, anticoagulantes o antiagregantes. (AU)

Introduction: superior vena cava syndrome results from an obstruction of blood flow through this vessel. Currently, almost all cases are associated with malignancies. There are controversies about the optimal management of this syndrome. Endovascular therapies are considered the first-line therapy. Material and methods: we collected clinical, laboratory and pharmacological data from patients admitted at the Hospital Italiano de Buenos Aires, between January 1st and November 1st 2021 with a diagnosis o superior vein cava syndrome. Baseline characteristics, treatment strategies and clinical outcomes were recorded. Results: a total of five patients were included in the present study. All cases were malignancy-related. Most of the patientsdeveloped moderate symptoms. Four out of five patients were treated with endovascular therapies and two patients died during hospitalization. Discussion: controversies regarding optimal management of the superior vena cava syndrome remain. Future research should focus on identifying those patients who are most likely to benefit from endovascular, anticoagulant or antiplatelet therapeutic strategies. (AU)

Antiplatelet and myocardial protective effect of Shexiang Tongxin Dropping Pill in patients undergoing percutaneous coronary intervention: A randomized controlled trial / 中西医结合学报

BACKGROUND@#High on-clopidogrel platelet reactivity could be partially explained by loss-of-function alleles of CYP2C19, the enzyme that converts clopidogrel into its active form. Shexiang Tongxin Dropping Pill (STDP) is a traditional Chinese medicine to treat angina pectoris. STDP has been shown to improve blood flow in patients with slow coronary flow and attenuate atherosclerosis in apolipoprotein E-deficient mice. However, whether STDP can affect platelet function remains unknown.@*OBJECTIVE@#The purpose of this study is to examine the potential effects of STDP on platelet function in patients undergoing percutaneous coronary intervention (PCI) for unstable angina. The interaction between the effects of STDP with polymorphisms of CYP2C19 was also investigated.@*DESIGN, PARTICIPANTS AND INTERVENTION@#This was a single-center, randomized controlled trial in patients undergoing elective PCI for unstable angina. Eligible subjects were randomized to receive STDP (210 mg per day) plus dual antiplatelet therapy (DAPT) with clopidogrel and aspirin or DAPT alone.@*MAIN OUTCOME MEASURES@#The primary outcome was platelet function, reflected by adenosine diphosphate (ADP)-induced platelet aggregation and platelet microparticles (PMPs). The secondary outcomes were major adverse cardiovascular events (MACEs) including recurrent ischemia or myocardial infarction, repeat PCI and cardiac death; blood biomarkers for myocardial injury including creatine kinase-MB isoenzyme (CK-MB) and high-sensitive troponin I (hsTnI); and biomarkers for inflammation including intercellular cell adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), monocyte chemoattractant protein-1 (MCP-1) and galectin-3.@*RESULTS@#A total of 118 subjects (mean age: [66.8 ± 8.9] years; male: 59.8%) were included into analysis: 58 in the control group and 60 in the STDP group. CYP2C19 genotype distribution was comparable between the 2 groups. In comparison to the control group, the STDP group had significantly lower CK-MB (P < 0.05) but similar hsTnI (P > 0.05) at 24 h after PCI, lower ICAM-1, VCAM-1, MCP-1 and galectin-3 at 3 months (all P < 0.05) but not at 7 days after PCI (P > 0.05). At 3 months, the STDP group had lower PMP number ([42.9 ± 37.3] vs. [67.8 ± 53.1] counts/μL in the control group, P = 0.05). Subgroup analysis showed that STDP increased percentage inhibition of ADP-induced platelet aggregation only in slow metabolizers (66.0% ± 20.8% in STDP group vs. 36.0% ± 28.1% in the control group, P < 0.05), but not in intermediate or fast metabolizers. The rate of MACEs during the 3-month follow-up did not differ between the two groups.@*CONCLUSION@#STDP produced antiplatelet, anti-inflammatory and cardioprotective effects. Subgroup analysis indicated that STDP inhibited residual platelet reactivity in slow metabolizers only.@*TRIAL REGISTRATION@#This study was registered on www.chictr.org.cn: ChiCTR-IPR-16009785.

A young patient with recurrent myocardial infarction within a half month / 中南大学学报(医学版)

In this study, we reported a young male patient with acute chest pain who was diagnosed as myocardial infarction. The regular medication was performed following coronary intervention. Under such condition, this patient had 3 times myocardial infarction within a half month. The laboratory results showed that there might be a state of hypercoagulability. Aspirin combined with clopidogrel and other treatment were administrated. Meanwhile, the examination demonstrated that there was aspirin-resistant in the patient. The antiplatelet drug and extended anticoagulation therapy were carried out. There was no further myocardial infarction, and no coronary arteries stenosis was found in the re-examination angiography. Aspirin resistance and hypercoagulability should be considered when patients occurred the repeated myocardial infarction after regular medication and coronary intervention. Replacement of the antiplatelet treatment or combination with anticoagulant therapy is necessary in similar patient to avoid the sever consequence.

JAG1 promotes migration, invasion, and adhesion of triple-negative breast cancer cells by promoting angiogenesis / 南方医科大学学报

OBJECTIVE@#To investigate the effect of JAG1 on the malignant phenotype of triple-negative breast cancer (TNBC) and its role in angiogenesis in breast cancer microenvironment.@*METHODS@#The expressions of Notch molecules were detected in human TNBC 231 and 231B cells using RT-qPCR. Five female nude mice were inoculated with 231 cells and another 5 with 231B cells into the mammary fat pads, and 4-6 weeks later, the tumors were collected for immunohistochemical and immunofluorescence tests. 231 cells and 231B cells were treated with recombinant JAG (rJAG) protein and DAPT, respectively, and changes in their malignant phenotypes were assessed using CCK-8 assay, Hoechst 33258 staining, wound healing assay, Transwell chamber assay and endothelial cell adhesion assay. Western blotting was used to detect the changes in the expressions of proteins related with the malignant phenotypes of 231 and 231B cells. The effects of conditioned medium (CM) derived from untreated 231 and 231 B cells, rJAG1-treated 231 cells and DAPT-treated 231B cells on proliferation and tube formation ability of cultured human umbilical vein endothelial cells (HUVECs) were evaluated using CCK-8 assay and tube-forming assay.@*RESULTS@#The expression of JAG1 was higher in 231B cells than in 231 cells (P < 0.05). Tumor 231B showed higher expression of VEGFA and CD31. Compared with 231-Blank group, the migration, invasion and adhesion of 231 cells in 231-rJAG1 were significantly enhanced (P < 0.05). Protein levels of Twist1 and Snail increased (P < 0.01), anti-apoptotic protein Bcl-2 increased (P < 0.05), while DAPT inhibited the related phenomena and indicators of 231B. The 231-rJAG1-CM increased the cell number and tubule number of HUVEC (P < 0.05).@*CONCLUSION@#JAG1 may affect the malignant phenotype of TNBC and promote angiogenesis in the tumor microenvironment.

Comparison on the clinical characteristics of patients with Takotsubo syndrome from China and from Europe/North America / 中华心血管病杂志

Objective: To summarize the clinical characteristics of patients with Takotsubo syndrome (TTS) from China and compare these features with patients from Europe/North America. Methods: We reviewed case reports published between 1990 and 2020 with the key words of "Takotsubo syndrome" "stress cardiomyopathy" "apical balloon syndrome" and "broken heart syndrome", in Wanfang, CNKI, Pubmed and Web of Science databases, and 1 294 articles were identified, including 128 articles reporting 163 cases in China and 1 166 articles reporting 1 256 cases in Europe/North America. The characteristics of demographics, triggers, symptoms, electrocardiogram, echocardiography, left ventriculogram,coronary angiography, treatment and prognosis were analyzed and compared between Chinese and European/North American cases. Results: A total of 1 294 articles (1 419 cases: 163 from China, 1 256 from Europe/North America) were included in the final analysis. The characteristics of Chinese cases included: (1) demographic:the age was (59.6±16.9) years, which was similar with that of European/North American ((59.7±17.4) years, P=0.90), and female accounting for 78.5% (128/163), which was lower than that of European/North American (85.4% (1 073/1 256), P=0.02). (2) Triggers:mental triggers accounted for 48.5% (79/163), physical triggers accounted for 43.6% (71/163), and no triggers accounted for 7.9% (13/163), respectively. Compared with Europe/North America, the ratio of patients with mental triggers was higher in China, while the ratio of patients with physical triggers and no triggers was lower (P<0.05). (3) Symptoms: chest pain (52.8% (86/163)), chest tightness (35.0% (57/163)), shortness of breath (33.1% (54/163)), dizziness (16.0% (26/163)), sweating (15.3% (25/163)), palpitations (12.3% (20/163)), syncope (9.2% (15/163)) abdominal pain/diarrhea (8.6% (14/163)), hypotension (7.4% (12/163)), and fatigue (1.2% (2/163)) were illustrated in sequence. Compared with patients in Europe/North America, the ratio of patients with chest tightness, dizziness, sweating, palpitations, abdominal pain/diarrhea was higher in Chinese patients, while the ratio of patients with hypotension was lower in Chinese patients (P<0.05). (4) Electrocardiogram: main manifestations were myocardial ischemia symptoms, such as ST-segment elevation (63.8% (104/163)), T wave inversion (46.0% (75/163)), ST-segment depression (8.6% (14/163)). Compared with European/North American, the ratio of patients with ST-segment elevation, T wave inversion, and atrioventricular block was higher in Chinese patients (P<0.05). (5) Echocardiography and imaging:apical dyskinesia (59.5% (97/163)) and apical/left ventricular bulbar dilation (36.2%(59/163)) dominated the echocardiography findings. Compared with European/North American, the ratio of patients with apical dyskinesia, apical/left ventricular bulbar dilation, and mitral regurgitation was higher in Chinese patients, while the ratio of patients with dyskinesia in other parts and left ventricular ejection fraction<50% was lower in Chinese patients (P<0.05). Left ventricular angiography showed 36.2% (59/163) of apical dyskinesia in Chinese patients, which was higher than that reported in European/North American patients, and 38.7% (63/163) of apical/left ventricular bulbar dilation was reported in Chinese patients, which was similar to that reported in European/North American patients. Coronary angiography showed percent of no stenosis or stenosis less than 50% was 87.1% (142/163), which was similar to that reported in European/North American patients (P>0.05). The typical type of TTS accounted for 96.3% (157/163), which was significantly higher than that reported in European/ American patients, while the ratio of basal type and midventricular type was lower (P<0.01). (6) Treatment and prognosis:the applied drugs in China were listed in order as following, β-blockers (41.1% (67/163)), antiplatelet agents (37.4%(61/163)), ACEI/ARB (36.2%(59/163)), anticoagulants (27.0%(44/163)), diuretics (19.6% (32/163)), etc. Compared with Europe/North America, the ratio of antiplatelet agents, anticoagulants, statins, diuretics, and nitrates use was higher in China (P<0.05), while the use of oxygen therapy and IABP was similar (P>0.05). The hospital mortality in China was 5.5% (9/163), during 1-year follow-up the recurrence rate was 3.7% (6/163) and the mortality was 0. The prognosis was similar with that in Europe/North America. Conclusions: Compared with TTS cases in Europe/North America, TTS cases in China also occur usually in middle-aged and elderly women, most of whom have mental/physical triggers and typical imaging manifestations, followed by a low hospital mortality rate and recurrence rate.