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BACKGROUND: Chronic kidney disease (CKD) and end-stage renal disease (ESRD) have been associated with worse outcomes after transcatheter aortic valve replacement (TAVR). With TAVR indications extending to a wider range of patient populations, it is important to understand the current implications of chronic renal insufficiency on clinical outcomes. We aim to determine the impact of CKD and ESRD on in-hospital outcomes after TAVR. METHODS: We queried the National Inpatient Sample for TAVR performed between 2016 and 2020 using International Classification of Diseases-10th Revision codes. We compared in-hospital mortality and clinical outcomes between three groups: normal renal function, CKD and ESRD. The association between CKD/ESRD and outcomes was tested with multivariable logistic regression analyses, using normal renal function as baseline. RESULTS: In the five-year study period, 279,195 patients underwent TAVR (mean age 78.9 ± 8.5 years, 44.4% female). Of all patients, 67.1% had normal renal function, 29.2% had CKD, and 3.7% had ESRD. There were significant differences in age, sex, and prevalence of comorbidities across groups. In-hospital mortality was 1.3%. Compared to patients with normal renal function, patients with renal insufficiency had higher in-hospital mortality, with the highest risk found in patients with ESRD (adjusted odds ratio: 1.4 [95% confidence interval: 1.2-1.7] for CKD; adjusted odds ratio: 2.4 [95% confidence interval: 1.8-3.3] for ESRD). Patients with CKD or ESRD had a higher risk of cardiogenic shock, need for mechanical circulatory support, and vascular access complications, compared to those with normal renal function. In addition, patients with ESRD had a higher risk of cardiac arrest and periprocedural acute myocardial infarction. The incidence of conversion to open heart surgery was 0.3% and did not differ between groups. Post-procedural infectious and respiratory complications were more common among patients with CKD or ESRD. CONCLUSION: Patients with CKD and ESRD are at higher risk of in-hospital mortality, cardiovascular, and non-cardiovascular complications after TAVR. The risk of complications is highest in patients with ESRD and does not result in more frequent conversion to open heart surgery. These results emphasize the importance of individualized patient selection for TAVR and procedural planning among patients with chronic renal insufficiency.
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Estenose da Valva Aórtica , Falência Renal Crônica , Insuficiência Renal Crônica , Substituição da Valva Aórtica Transcateter , Humanos , Feminino , Idoso , Idoso de 80 Anos ou mais , Masculino , Substituição da Valva Aórtica Transcateter/efeitos adversos , Estenose da Valva Aórtica/diagnóstico por imagem , Estenose da Valva Aórtica/cirurgia , Estenose da Valva Aórtica/complicações , Fatores de Risco , Resultado do Tratamento , Falência Renal Crônica/diagnóstico , Falência Renal Crônica/epidemiologia , Falência Renal Crônica/terapia , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/epidemiologia , Insuficiência Renal Crônica/terapia , Valva Aórtica/cirurgiaRESUMO
BACKGROUND: Pattern mining techniques are helpful tools when extracting new knowledge in real practice, but the overwhelming number of patterns is still a limiting factor in the health-care domain. Current efforts concerning the definition of measures of interest for patterns are focused on reducing the number of patterns and quantifying their relevance (utility/usefulness). However, although the temporal dimension plays a key role in medical records, few efforts have been made to extract temporal knowledge about the patient's evolution from multivariate sequential patterns. METHODS: In this paper, we propose a method to extract a new type of patterns in the clinical domain called Jumping Diagnostic Odds Ratio Sequential Patterns (JDORSP). The aim of this method is to employ the odds ratio to identify a concise set of sequential patterns that represent a patient's state with a statistically significant protection factor (i.e., a pattern associated with patients that survive) and those extensions whose evolution suddenly changes the patient's clinical state, thus making the sequential patterns a statistically significant risk factor (i.e., a pattern associated with patients that do not survive), or vice versa. RESULTS: The results of our experiments highlight that our method reduces the number of sequential patterns obtained with state-of-the-art pattern reduction methods by over 95%. Only by achieving this drastic reduction can medical experts carry out a comprehensive clinical evaluation of the patterns that might be considered medical knowledge regarding the temporal evolution of the patients. We have evaluated the surprisingness and relevance of the sequential patterns with clinicians, and the most interesting fact is the high surprisingness of the extensions of the patterns that become a protection factor, that is, the patients that recover after several days of being at high risk of dying. CONCLUSIONS: Our proposed method with which to extract JDORSP generates a set of interpretable multivariate sequential patterns with new knowledge regarding the temporal evolution of the patients. The number of patterns is greatly reduced when compared to those generated by other methods and measures of interest. An additional advantage of this method is that it does not require any parameters or thresholds, and that the reduced number of patterns allows a manual evaluation.
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Mineração de Dados , Humanos , Razão de Chances , Mineração de Dados/métodos , Fatores de Tempo , Reconhecimento Automatizado de Padrão , Atenção à Saúde , Registros Eletrônicos de SaúdeRESUMO
INTRODUCTION: Left atrial appendage closure (LAAC) is an intervention aimed at stroke prevention in nonvalvular atrial fibrillation (AF). There is a three-fold increased risk of stroke in patients with concomitant presence of AF and heart failure (HF). While anticoagulation is effective, only 60% receive it. We aimed at studying the safety of LAAC in HF patients using a national all-payer database. METHODS: We queried the National Inpatient Sample for the year 2016-2018 for WATCHMAN device insertion using ICD 10 procedure codes. We divided the study population into HF and non-HF groups. Outcomes were compared using appropriate statistical tests, p< .05 was considered significant. RESULTS: 34 385 LAAC procedures were identified of which 8530 (24.8%) were done in patients with HF. The mean (SD) age of the study population was 76 (7.9) years and 42% were female. There was no difference in mean age between HF and non-HF groups. Our findings indicate that there is no difference in inpatient mortality and cardiac complications between the HF and non-HF groups. However, noncardiac complications including acute kidney injury and respiratory failure were higher in the HF group. CONCLUSION: LAAC appears to be a safe procedure in patients with HF. The study is limited by a short follow up period and long-term follow-up is required before definitive conclusions can be made.
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Apêndice Atrial , Fibrilação Atrial , Insuficiência Cardíaca , Acidente Vascular Cerebral , Humanos , Feminino , Idoso , Masculino , Apêndice Atrial/cirurgia , Resultado do Tratamento , Fibrilação Atrial/complicações , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/cirurgia , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/prevenção & controle , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/terapia , Insuficiência Cardíaca/complicações , AnticoagulantesRESUMO
PURPOSE OF REVIEW: Drug-eluting stents are used in nearly all cases of percutaneous coronary revascularization and have been shown to be superior to balloon angioplasty or bare metal stents. The designs of these stents are continually evolving to maximize efficacy and safety. RECENT FINDINGS: This review outlines the important components of a drug-eluting stent and highlights the changes in stent design that have led to the optimization of clinical outcomes. Most stents used in contemporary times are thin strut, durable polymer drug-eluting stents (DES) that elute either everolimus or zotarolimus. Newer DES designs incorporating bioresorbable polymers or ultrathin struts have shown encouraging safety and efficacy profiles. DES are essential for the management of patients with obstructive coronary artery disease and are used in most coronary interventions. Changes in stent designs over the past 30 years reflect the ongoing need to address the limitations of earlier stents aimed to improve patient outcomes.
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Fármacos Cardiovasculares , Doença da Artéria Coronariana , Stents Farmacológicos , Intervenção Coronária Percutânea , Implantes Absorvíveis , Doença da Artéria Coronariana/cirurgia , Humanos , Polímeros , Desenho de Prótese , Stents , Resultado do TratamentoRESUMO
Heart transplant (HT) recipients are more frequently reaching childbearing age given improvement in median survival and outcomes after HT. Although most pregnancies in HT recipients have favorable outcomes, poor fetal outcomes and maternal complications such as hypertensive disorders of pregnancy are more common in HT recipients than in the general population. In this review, we summarize the current evidence to guide the management of pregnancy in HT recipients. Preconception counseling, focused on risk stratification and optimal timing of conception, is the first important step to optimize pregnancy outcomes. During pregnancy and in the postpartum period, frequent monitoring of graft function and immunosuppressive levels is recommended. Calcineurin inhibitors and corticosteroids should be the mainstay of treatment for both prevention and treatment of graft rejection. Delivery planning should follow usual obstetric indications, preferably with vaginal delivery at term using regional anesthesia. A multidisciplinary care team should be involved in management through all stages of pregnancy to ensure success.
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While most coronavirus 2019 (COVID-19) survivors have had complete resolution of symptoms, a significant proportion have suffered from incomplete recovery. Cardiopulmonary symptoms, such as dyspnea, chest pain, and palpitations are responsible for a substantial symptom burden in COVID-19 survivors. Studies have revealed persistent myocardial injury with late gadolinium enhancement and myocardial scar on cardiac magnetic resonance in a significant proportion of patients. Evidence of myocardial edema, active inflammation, left ventricular dysfunction, and right ventricular dysfunction, is limited to a minority of patients. Large observational studies of COVID-19 survivors have indicated an increased risk of cardiovascular disease compared to the general population, including the risk of coronary artery disease, cardiomyopathy, and arrhythmias. Management of long COVID is focused on supportive therapy to reduce systemic inflammation. Patients with high cardiovascular risk, namely, those who had cardiovascular complications during acute illness, patients who have new onset cardiopulmonary symptoms in the postinfectious period, and competitive athletes, should be evaluated by a cardiovascular specialist. Management of cardiovascular sequelae is currently based on general expert guideline recommendations given the lack of evidence specific to long COVID syndrome. In this review, we outline the cardiovascular manifestations of long COVID, the current evidence supporting cardiac abnormalities in the postinfectious period, and the recommended management of these patients.
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The optimal duration of anticoagulation in patients with left ventricular thrombus (LVT) is unknown. The data package herein presented contains the information used to assess the effect of duration of anticoagulation in the incidence of stroke in patients with left ventricular thrombus (LVT) in a tertiary hospital. In order to collect the required data, all transthoracic echocardiography studies at our institution from January 1st 2014 to December 31st 2021 with LVT were retrieved using dedicated software (Phillips Intellispace Cardiovascular; Koninklijke Phillips N.V., 2004-2020). Second, a dataset was designed ad hoc for this study in which the recruited data for the predefined objectives were obtained from electronic medical records. These data included clinical and demographic information including treatment choices (vitamin K antagonists [VKA] versus direct oral anticoagulants [DOAC]), duration of treatment, reason for interruption of treatment, occurrence of stroke, acute myocardial infarction, bleeding events, thrombus resolution, recurrence, and death. Retrieved data were stored in an excel sheet for analysis using the statistical package STATA (StataCorp v. 15.0, College station, TX). This methodology allows the reuse of these data for further analysis, in the context of the present study and also for future recruitment of additional patients from other institutions to increase statistical power.
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BACKGROUND: General anesthesia (GA) is the standard anesthetic approach for subcutaneous implantable cardioverter-defibrillator (S-ICD) implantation. Nonetheless, GA is expensive and can be associated with adverse events. Tumescent local anesthesia (TLA) has been shown to reduce in-room and procedural times and to decrease post-procedural pain, all of which could result in a reduction in procedure-related costs. OBJECTIVE: The purpose of this study is to compare the cost-effectiveness of GA and TLA in patients undergoing S-ICD implantation. METHODS: The present study is a prospective, nonrandomized, controlled study of patients who underwent S-ICD implantation between 2019 and 2022. Patients were allocated to either the TLA or the GA group. We performed a cost analysis for each intervention. As an effectiveness measure, the 0-10 point Numeric Pain Rating Scale at 1, 12, and 24 hours post-implantation was analyzed and compared between the groups. A score of 0 was considered no pain; 1-5, mild pain; 6-7, moderate pain; and 8-10, severe pain. Cost-effectiveness was calculated using incremental cost-effectiveness ratios. RESULTS: Seventy patients underwent successful S-ICD implantation. The total cost of the electrophysiology laboratory was higher in the GA group than in the TLA group (median ± interquartile range US$55,824 ± US$29,411 vs US$37,222 ± US$24,293; P < .001), with a net saving of $20,821 when compared with GA for each S-ICD implantation. There was a significant decrease in post-procedural pain scores in the TLA group when compared with the GA group (repeated measures analysis of variance, P = .009; median ± interquartile range 0 ± 3 vs 0 ± 5 at 1 hour, P = .058; 3 ± 4 vs 6 ± 8 at 12 hours, P = .030; 0 ± 4 vs 2 ± 6 at 24 hours, P = .040). CONCLUSION: TLA is a more cost-effective alternative to GA for S-ICD implantation, with both direct and indirect cost reductions. Importantly, these reduced costs are associated with reduced postprocedural pain.
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Desfibriladores Implantáveis , Dor Processual , Humanos , Anestesia Local , Desfibriladores Implantáveis/efeitos adversos , Estudos Prospectivos , Análise de Custo-Efetividade , Anestesia Geral/efeitos adversos , Dor , Resultado do TratamentoRESUMO
INTRODUCTION: Mineralocorticoid receptor antagonists (MRAs) improve cardiovascular outcomes in patients with heart failure. These benefits of MRAs vary in different heart failure populations based on left ventricular ejection fraction and associated comorbidities. AREAS COVERED: We define the pharmacologic properties of MRAs and the pathophysiological rationale for their utility in heart failure. We outline the current literature on the use of MRAs in different heart failure populations, including reduced and preserved ejection fraction (HFrEF/HFpEF) and acute heart failure decompensation. Finally, we describe the limitations of currently available data and propose future directions of study. EXPERT OPINION: While there is strong evidence supporting the use of MRAs in HFrEF, evidence in patients with HFpEF or acute heart failure is less definitive. Comorbidities such as obesity or atrial fibrillation could be clinical modifiers of the response to MRAs and potentially alter the risk/benefit ratio in these subpopulations. Emerging evidence for new non-steroidal MRAs reveal promising preliminary results that, if confirmed in large randomized clinical trials, could favor a change in clinical practice.
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Insuficiência Cardíaca , Antagonistas de Receptores de Mineralocorticoides , Humanos , Antagonistas de Receptores de Mineralocorticoides/uso terapêutico , Insuficiência Cardíaca/induzido quimicamente , Volume Sistólico/fisiologia , Função Ventricular Esquerda , Espironolactona/efeitos adversosRESUMO
Risk factors associated with in-hospital mortality in young patients with ST-segment elevation myocardial infarction are poorly described. In addition, it is increasingly recognized that these risk factors might differ from those of older patients. The dataset herein presented describes the association between different variables and in-hospital mortality in patients <55 years old with ST-segment elevation myocardial infarction. This data supplements the manuscript "Sex Related Differences in the Treatment of ST-Segment Elevation Acute Myocardial Infarction in Patients Aged <55 Years" (Lorente-Ros et al.) Data for this data in brief article were obtained from a prospective database of patients <55 years old with confirmed ST-segment elevation myocardial infarction admitted to a tertiary care hospital during an 11-year period. The data were collected via review of the clinical charts. The dataset describes the relative risk and 95% confidence interval of in-hospital mortality for each variable, including cardiovascular risk factors, angiographic findings, treatment received, and complications developed. Patients in this dataset represent a unique population, given that it only includes confirmed ST-segment elevation myocardial infarction while excluding other types of acute coronary syndrome, the patient's young age, and the reflection of contemporary up-to-date practices. This dataset will be valuable to further build on knowledge on the prognostic markers of acute myocardial infarction in a younger patient population.
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BACKGROUND: It is important to exploit all available data on patients in settings such as intensive care burn units (ICBUs), where several variables are recorded over time. It is possible to take advantage of the multivariate patterns that model the evolution of patients to predict their survival. However, pattern discovery algorithms generate a large number of patterns, of which only some are relevant for classification. OBJECTIVE: We propose to use the diagnostic odds ratio (DOR) to select multivariate sequential patterns used in the classification in a clinical domain, rather than employing frequency properties. METHODS: We used data obtained from the ICBU at the University Hospital of Getafe, where 6 temporal variables for 465 patients were registered every day during 5 days, and to model the evolution of these clinical variables, we used multivariate sequential patterns by applying 2 different discretization methods for the continuous attributes. We compared 4 ways in which to employ the DOR for pattern selection: (1) we used it as a threshold to select patterns with a minimum DOR; (2) we selected patterns whose differential DORs are higher than a threshold with regard to their extensions; (3) we selected patterns whose DOR CIs do not overlap; and (4) we proposed the combination of threshold and nonoverlapping CIs to select the most discriminative patterns. As a baseline, we compared our proposals with Jumping Emerging Patterns, one of the most frequently used techniques for pattern selection that utilizes frequency properties. RESULTS: We have compared the number and length of the patterns eventually selected, classification performance, and pattern and model interpretability. We show that discretization has a great impact on the accuracy of the classification model, but that a trade-off must be found between classification accuracy and the physicians' capacity to interpret the patterns obtained. We have also identified that the experiments combining threshold and nonoverlapping CIs (Option 4) obtained the fewest number of patterns but also with the smallest size, thus implying the loss of an acceptable accuracy with regard to clinician interpretation. The best classification model according to the trade-off is a JRIP classifier with only 5 patterns (20 items) that was built using unsupervised correlation preserving discretization and differential DOR in a beam search for the best pattern. It achieves a specificity of 56.32% and an area under the receiver operating characteristic curve of 0.767. CONCLUSIONS: A method for the classification of patients' survival can benefit from the use of sequential patterns, as these patterns consider knowledge about the temporal evolution of the variables in the case of ICBU. We have proved that the DOR can be used in several ways, and that it is a suitable measure to select discriminative and interpretable quality patterns.
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Gender-related differences after ST-segment elevation myocardial infarction (STEMI) have been reported, but studies have generally focused on high-risk groups and results are inconsistent. This study aims to determine gender-related differences in the treatment of STEMI and in-hospital mortality in a contemporary cohort of young patients. We included patients aged <55 years admitted to the Acute Cardiac Care Unit with STEMI during an 11-year period. We retrospectively reviewed the clinical charts to register information on demographics, clinical and laboratory data, angiography, treatment received, complications, and in-hospital mortality. A total of 812 patients were included (712 men and 100 women). There were no gender-related differences in age or prevalence of cardiovascular risk factors. Women, as compared with men, had higher incidence of nonobstructive angiography (14.0% vs 2.4%) and coronary tortuosity (4.0% vs 0.8%), and lower incidence of multivessel disease (35.0% vs 49.6%) (p <0.05). Less frequently than men, women received percutaneous transluminal coronary angioplasty (94.0% vs 98.2%), and stent placement (82.0% vs 93.8%), inotropic agents (2.0% vs 8.3%), hypothermia after cardiac arrest (25.0% vs 84.0%), and mechanical ventilation (4.0% vs 11.0%) (p <0.05). These differences were not explained by the different angiographic findings. In-hospital mortality was 2.0% and 3.4%, in women and men, respectively (adjusted odds ratio 0.712, 95% confidence interval 0.164 to 3.093, p = 0.650). In conclusion, women aged <55 years with STEMI were held to different treatment standards than men.
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Infarto do Miocárdio , Intervenção Coronária Percutânea , Infarto do Miocárdio com Supradesnível do Segmento ST , Feminino , Mortalidade Hospitalar , Humanos , Masculino , Infarto do Miocárdio/epidemiologia , Intervenção Coronária Percutânea/efeitos adversos , Estudos Retrospectivos , Fatores de Risco , Infarto do Miocárdio com Supradesnível do Segmento ST/epidemiologia , Infarto do Miocárdio com Supradesnível do Segmento ST/etiologia , Infarto do Miocárdio com Supradesnível do Segmento ST/terapia , Fatores Sexuais , Resultado do TratamentoRESUMO
There have been no studies focusing on how pulmonary hypertension (PH) affects inpatient outcomes in patients with hypertrophic cardiomyopathy (HCM) hospitalized for acute decompensated heart failure or cardiogenic shock. This study explores inpatient outcomes of patients with HCM, and concomitant PH compared to patients with HCM. Based on the National Inpatient Sample (NIS) 2016-2018, patients admitted with a primary diagnosis of acute decompensated heart failure or cardiogenic shock were selected. The patients diagnosed with concomitant HCM were identified and divided into 2 groups based on the presence or absence of PH. After propensity matching 1545 matched pairs were generated. Patients with PH had a higher prevalence of chronic kidney disease (P < 0.001), anemia (P < 0.001), coagulopathy (P < 0.001), atrial fibrillation (Pâ¯=â¯0.031), and valvular disease (P < 0.001) (Table 1). The primary outcome (all-cause in-hospital mortality) occurred in 110 patients (2.6%) without PH and 95 patients (5.2%) with PH, which was not statistically significant after propensity matching (odds ratio [OR]:1.53; 95% confidence interval [CI]: 0.70-3.33; Pâ¯=â¯0. 28) (Table 3). Patients with PH had a higher incidence of transient ischemic attack (TIA) (OR: 9.52; 95% CI: 3.38-26.78; P < 0.001)] and respiratory failure [(OR: 1.49; 95% CI:1.05-2.11; Pâ¯=â¯0.027], although with no difference in requirement for mechanical ventilation (= 0.64), as compared to patients without PH. PH in patients with HCM is associated with increased morbidity, including increased risk of TIA and respiratory failure.
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Fibrilação Atrial , Cardiomiopatia Hipertrófica , Insuficiência Cardíaca , Hipertensão Pulmonar , Ataque Isquêmico Transitório , Insuficiência Respiratória , Fibrilação Atrial/complicações , Cardiomiopatia Hipertrófica/complicações , Cardiomiopatia Hipertrófica/diagnóstico , Cardiomiopatia Hipertrófica/epidemiologia , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/epidemiologia , Humanos , Hipertensão Pulmonar/diagnóstico , Hipertensão Pulmonar/epidemiologia , Hipertensão Pulmonar/etiologia , Ataque Isquêmico Transitório/complicações , Insuficiência Respiratória/complicações , Insuficiência Respiratória/epidemiologia , Fatores de Risco , Choque Cardiogênico/diagnóstico , Choque Cardiogênico/epidemiologia , Choque Cardiogênico/etiologiaRESUMO
The optimal duration of anticoagulation in patients with left-ventricular thrombus (LVT) is unclear. In the present study, we aimed to analyze the effect of treatment duration (≤12 months [short-term anticoagulation, (STA)] versus >12 months [long-term anticoagulation, (LTA)]) in the incidence of stroke and other secondary outcomes (acute myocardial infarction, bleeding, and mortality). Multivariate Cox regression was used to determine the association between treatment duration and stroke, adjusted for baseline embolic risk. A total of 98 cases of LVT (age 64.3 ± 12.8 years, female 18 [18%]) were identified. Sixty-one patients (62%) received LTA. Patients receiving LTA were older than those receiving STA (66.5 ± 11.6 vs 60.7 ± 13.9 years, p = 0.029), more often had atrial fibrillation (31% vs 0%, p <0.001), and had a higher CHA2DS2-VASc score (4.3 ± 1.6 vs 3.6 ± 1.6, p = 0.046). Stroke occurred in 2 and 10 patients (3% vs 27%, p <0.001), acute myocardial infarction in 2 and 3 patients (3% vs 8%, p = 0.292), bleeding in 4 and 3 patients (7% vs 8%, p = 0.773), and mortality in 12 and 7 patients (20% vs 19%, p = 0.927) in the LTA and STA groups, respectively. In multivariate analysis, after adjusting for embolic risk, LTA was associated with decreased risk of stroke at 5 years (adjusted hazard ratio 0.16; 95% confidence interval 0.03 to 0.72, p = 0.017). In conclusion, our data suggest that prolonged anticoagulation in patients with LVT may be associated with significantly lower risk of stroke.
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Fibrilação Atrial , Embolia , Infarto do Miocárdio , Acidente Vascular Cerebral , Trombose , Humanos , Feminino , Pessoa de Meia-Idade , Idoso , Anticoagulantes/uso terapêutico , Incidência , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/prevenção & controle , Fibrilação Atrial/complicações , Fibrilação Atrial/tratamento farmacológico , Fibrilação Atrial/epidemiologia , Hemorragia/epidemiologia , Trombose/epidemiologia , Trombose/complicações , Embolia/epidemiologia , Infarto do Miocárdio/epidemiologia , Fatores de Risco , Medição de Risco , Estudos RetrospectivosRESUMO
INTRODUCTION: Despite tremendous advances, the shortcomings of current therapies for coronary disease are evidenced by the fact that it remains the leading cause of death in many parts of the world. There is hence a drive to develop novel therapies to tackle this disease. Therapeutic approaches to coronary angiogenesis have long been an area of interest in lieu of its incredible, albeit unrealized potential. AREAS COVERED: This paper offers an overview of mechanisms of native angiogenesis and a description of angiogenic growth factors. It progresses to outline the advances in gene and stem cell therapy and provides a brief description of other investigational approaches to promote angiogenesis. Finally, the hurdles and limitations unique to this particular area of study are discussed. EXPERT OPINION: An effective, sustained, and safe therapeutic option for angiogenesis truly could be the paradigm shift for cardiovascular medicine. Unfortunately, clinically meaningful therapeutic options remain elusive because promising animal studies have not been replicated in human trials. The sheer complexity of this process means that numerous major hurdles remain before therapeutic angiogenesis truly makes its way from the bench to the bedside.
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Doença da Artéria Coronariana/terapia , Neovascularização Fisiológica/fisiologia , Indutores da Angiogênese/farmacologia , Animais , Doença da Artéria Coronariana/fisiopatologia , Terapia Genética/métodos , Humanos , Transplante de Células-Tronco/métodosRESUMO
Severe acute respiratory syndrome coronavirus 2 infections are associated with greater risk of both arterial and venous thromboembolic events.Pathophysiology and Clinical implications: This has been attributed to a florid proinflammatory state resulting in microvascular dysfunction, activation of platelets and procoagulant systems as well as possible direct endothelial injury. The associated morbidity and mortality of these events has prompted much speculation and varied anticoagulation and fibrinolytic strategies based on multiple criteria including disease severity and biomarkers. No clear definitive benefit has been established with these approaches, which have frequently led to greater bleeding complications without significant mortality benefit.Overview: In this review, we outline the burden of these thromboembolic events in coronavirus disease-2019 (COVID-19) as well as the hypothesized contributory biological mechanisms. Finally, we provide a brief overview of the major clinical studies on the topic, and end with a summary of major societal guideline recommendations on anticoagulation in COVID-19.
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Transtornos da Coagulação Sanguínea/etiologia , Coagulação Sanguínea , COVID-19/complicações , Anticoagulantes/uso terapêutico , Plaquetas/virologia , COVID-19/virologia , Humanos , Fatores de Risco , Tromboembolia Venosa/etiologia , Trombose Venosa/etiologia , Tratamento Farmacológico da COVID-19RESUMO
INTRODUCTION: Hirschsprung disease is caused by an impairment in cell migration from the neural crest to the gastrointestinal tract, resulting in an absence of neurons in the myenteric plexus. Many mutations in several genes have been associated to Hirschsprung disease; most of them affecting the RET proto-oncogen pathway. The purpose of this study is the description of novel and known mutations in genes associated to Hirschsprung disease and their prognostic implications. MATERIAL AND METHODS: Retrospective analysis of patients with Hirschsprung disease and positive genetic studies evaluated from 1970 to 2013. RESULTS: We found 21 positive genetic studies in the global series, 17 of them involving the RET proto-oncogene. Two of the mutations are novel and they have not been reported in the medical literature. CONCLUSIONS: The RET protooncogene is the main gene associated with Hirschsprung disease. There are still multiple unknown mutations related to the pathogenesis of the disease. The study of this gene must be part of the work-up of all patients with Hirschsprung disease, as well as their first degree relatives if the mutation is associated with MEN2A and MEN2B syndromes.
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Doença de Hirschsprung/genética , Mutação , Proteínas Proto-Oncogênicas c-ret/genética , Feminino , Marcadores Genéticos , Testes Genéticos , Doença de Hirschsprung/diagnóstico , Humanos , Recém-Nascido , Masculino , Prognóstico , Proto-Oncogene Mas , Estudos RetrospectivosRESUMO
INTRODUCTION: Hirschsprung Disease is caused by an impairment in cell migration from the neural crest to the gastrointestinal tract, resulting in an absence of neurons in the myenteric plexus. Many mutations in several genes have been associated to Hirschsprung disease; most of them affecting the RET proto-oncogen pathway. The purpose of this study is the description of novel and known mutations in genes associated to Hirschsprung disease and their prognostic implications. MATERIAL AND METHODS: Retrospective analysis of patients with Hirschsprung disease and positive genetic studies evaluated from 1970 to 2013. RESULTS: We found 21 positive genetic studies in the global series, 17 of them involving the RET proto-oncogene: Two of the mutations are novel and they have not been reported in the medical literature. CONCLUSIONS: The RET protooncogene is the main gene associated with Hirschsprung disease. There are still multiple unknown mutations related to the pathogenesis of the disease. The study of this gene must be part of the work-up of all patients with Hirschsprung disease, as well as their first degree relatives if the mutation is associated with MEN2A and MEN2B syndromes.