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This study aims to assess the potential bioactivity of newly designed benzodiazepine-1,2,3-triazole derivatives using in-silico methodologies, with a primary focus on elucidating their inhibitory interactions with the butyrylcholinesterase (BuChE) enzyme, which is implicated in Alzheimer's disease. We employed multiple linear regression (MLR) methods to conduct a quantitative structure-activity relationship (QSAR) analysis on a collection of 31 benzodiazepine-1,2,3-triazole derivatives, with the goal of investigating, assessing, and predicting their activities, as well as designing novel compounds. This approach yielded highly accurate results, with coefficients of determination (R²) of 0.77 and 0.81 for the training and test datasets, respectively. Additionally, the optimized compounds were subjected to an Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET) analysis, demonstrating their potential as non-hepatotoxic agents with enhanced absorption and blood-brain barrier permeability. To further validate these findings, the most favorable docking conformations were analyzed using molecular dynamics (MD) simulations with GROMACS software, predicting the stability of the formed complexes. These simulations underscored the critical role of hydrogen bonds in stabilizing the compounds at the BuChE receptor binding site. The results hold great promise for the development of innovative benzodiazepine-1,2,3-triazole derivatives as effective BuChE inhibitors, potentially leading to therapeutic interventions for Alzheimer's disease.
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INTRODUCTION: Data regarding ventricular tachycardia (VT) or premature ventricular complex (PVC) ablation in patients with aortic valve (AV) intervention (AVI) is limited. Catheter ablation (CA) can be challenging given perivalvular substrate in the setting of prosthetic valves. We sought to investigate the characteristics, safety, and outcomes of CA in patients with prior AVI and ventricular arrhythmias (VA). METHODS: We identified consecutive patients with prior AVI (replacement or repair) who underwent CA for VT or PVC between 2013 and 2018. We investigated the mechanism of arrhythmia, ablation approach, perioperative complications, and outcomes. RESULTS: We included 34 patients (88% men, mean age 64 ± 10.4 years, left ventricular (LV) ejection fraction 35.2 ± 15.0%) with prior AVI who underwent CA (22 VT; 12 PVC). LV access was obtained through trans-septal approach in all patients except one patient who had percutaneous transapical access. One patient had combined retrograde aortic and trans-septal approach. Scar-related reentry was the dominant mechanism of induced VTs. Two patients had bundle branch reentry VTs. In the VT group, substrate mapping demonstrated heterogeneous scar that involved the peri-AV area in 95%. Despite that, the site of successful ablation included the periaortic region only in 6 (27%) patients. In the PVC group, signal abnormalities consistent with scar in the periaortic area were noted in 4 (33%) patients. In 8 (67%) patients, the successful site of ablation was unrelated to the periaortic area. No procedure-related complications occurred. The survival and recurrence-free survival rate at 1 year tended to be lower in VT group than in PVC group (p = .06 and p = .05, respectively) with a 1-year recurrence-free survival rate of 52.8% and 91.7%, respectively. No arrhythmia-related death was documented on long-term follow-up. CONCLUSION: CA of VAs can be performed safely and effectively in patients with prior AVI.
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Ablação por Cateter , Taquicardia Ventricular , Masculino , Humanos , Pessoa de Meia-Idade , Idoso , Feminino , Valva Aórtica/diagnóstico por imagem , Valva Aórtica/cirurgia , Resultado do Tratamento , Cicatriz/etiologia , Taquicardia Ventricular/diagnóstico , Taquicardia Ventricular/etiologia , Taquicardia Ventricular/cirurgia , Sistema de Condução Cardíaco , Ablação por Cateter/efeitos adversosRESUMO
Depression is a common and devastating mental illness associated with increased morbidity and mortality, partially due to elevated rates of suicidal attempts and death. Select patients with end-stage heart failure on a waiting-list for a donor heart undergo left ventricular assist device (LVAD) implantation. The LVAD provides a circulatory flow of oxygenated blood to the body, mimicking heart functionality by operating on a mechanical technique. LVAD improves functional capacity and survivability among patients with end-stage heart failure. However, accumulating data suggests that LVAD recipients suffer from an increased incidence of depression and suicide attempts. There is scarce knowledge regarding the pathological mechanism and appropriate treatment approach for depressed LVAD patients. This article summarizes the current evidence on the association between LVAD implantation and occurrence of depression, suggesting possible pathological mechanisms underlying the device-associated depression and reviewing the current treatment strategies. The summarized data underscores the need for a rigorous pre-(LVAD)-implantation psychiatric evaluation, continued post-implantation mental health assessment, and administration of antidepressant treatment as necessary.
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Insuficiência Cardíaca , Transplante de Coração , Coração Auxiliar , Humanos , Coração Auxiliar/efeitos adversos , Depressão/etiologia , Transplante de Coração/efeitos adversos , Resultado do Tratamento , Doadores de Tecidos , Assistência ao Paciente/efeitos adversos , Estudos RetrospectivosRESUMO
We report the case of a 51-year-old female with history of end stage renal disease on hemodialysis who presented with right hemiplegia and aphasia. On admission, head CT was negative for intracranial hemorrhage. MRI showed an area of acute infarct in the left parietal lobe. The patient received intravenous tissue plasminogen activator. Head CT 24 hours later showed areas of increased density in the left parietal and posterior temporal lobes. Contrast extravasation with superimposed intracranial hemorrhage could not be excluded. Therefore, antiplatelet therapy was held. A follow up CT scan demonstrated the same findings. Another head CT was obtained after hemodialysis showed resolution of the previously noted areas of increased density suggesting that contrast extravasation was the reason of increased density areas.
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Acidente Vascular Cerebral , Ativador de Plasminogênio Tecidual , Feminino , Humanos , Pessoa de Meia-Idade , Hemorragias Intracranianas , Terapia Trombolítica , Extravasamento de Materiais Terapêuticos e Diagnósticos , Imageamento por Ressonância Magnética , Acidente Vascular Cerebral/tratamento farmacológicoRESUMO
Statins have grown to become an important class of medications in the primary and secondary prevention of cardiovascular diseases. While lowering low-density lipoprotein-C (LDL-C) levels, statins also have a role in stabilization and regression of atherosclerotic plaques. In the last two decades, there is a mounting body of evidence that suggests that statins and lowering serum lipid levels may be associated with an increased risk of developing intracerebral hemorrhage (ICH). This review article provides a concise summary of the most important studies performed to date and the pathophysiology behind the association between statins and ICH.
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Inibidores de Hidroximetilglutaril-CoA Redutases , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Hemorragia Cerebral/induzido quimicamente , Hemorragia Cerebral/tratamento farmacológico , Prevenção SecundáriaRESUMO
BACKGROUND: Data regarding ventricular tachycardia (VT) or premature ventricular complex (PVC) ablation following mitral valve surgery (MVS) is limited. Catheter ablation (CA) can be challenging given perivalvular substrate in the setting of mitral annuloplasty or prosthetic valves. OBJECTIVE: To investigate the characteristics, safety, and outcomes of radiofrequency CA in patients with prior MVS and ventricular arrhythmias (VA). METHODS: We identified consecutive patients with prior MVS who underwent CA for VT or PVC between January 2013 and December 2018. We investigated the mechanism of arrhythmia, ablation approach, peri-operative complications, and outcomes. RESULTS: In our cohort, 31 patients (77% men, mean age 62.3 ± 10.8 years, left ventricular ejection fraction 39.2 ± 13.9%) with prior MVS underwent CA (16 VT; 15 PVC). Access to the left ventricle was via transseptal approach in 17 patients, and a retrograde aortic approach was used in 13 patients. A combined transseptal and retrograde aortic approach was used in one patient, and a percutaneous epicardial approach was combined with trans-septal approach in one patient. Heterogenous scar regions were present in 94% of VT patients and scar-related reentry was the dominant mechanism of VT. Forty-seven percent of PVC patients had abnormal substrate at the site targeted for ablation. Clinical VA substrates involved the peri-mitral area in six patients with VT and five patients with PVC ablation. No procedure-related complications were reported. The overall recurrence-free rate at 1-year was 72.2%; 67% in the VT group and 78% in the PVC group. No arrhythmia-related death was documented on long-term follow-up. CONCLUSION: CA of VAs can be performed safely and effectively in patients with MVS.
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Ablação por Cateter , Taquicardia Ventricular , Complexos Ventriculares Prematuros , Idoso , Ablação por Cateter/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valva Mitral/diagnóstico por imagem , Valva Mitral/cirurgia , Volume Sistólico , Taquicardia Ventricular/diagnóstico , Taquicardia Ventricular/etiologia , Taquicardia Ventricular/cirurgia , Resultado do Tratamento , Função Ventricular Esquerda , Complexos Ventriculares Prematuros/diagnóstico , Complexos Ventriculares Prematuros/etiologia , Complexos Ventriculares Prematuros/cirurgiaRESUMO
BACKGROUND: Transcatheter aortic valve implantation (TAVI) has increasingly been utilized in patients with bicuspid aortic valve (BAV) related aortic stenosis (AS) with insufficient large-scale data on its safety. METHODS: The Nationwide Inpatient Sample and Nationwide Readmission Database (2011-2018) were queried to identify patients undergoing TAVI for BAV versus trileaflet aortic valve (TAV) associated AS. The in-hospital, 30- and 180-day odds of outcomes were assessed using a propensity-matched analysis (PSM) to calculate adjusted odds ratios (aOR) with its 95% confidence interval (CI). RESULTS: A total of 216,723 TAVI (TAV: 214,050 and BAV: 2,673) crude and 5,347 matched population (TAV: 2,674 and BAV: 2,673) was included in the final analysis. At index admission, the adjusted odds of in-hospital mortality (aOR: 1.57, 95% CI: 0.67-3.66), stroke (aOR: 0.77, 95% CI: 0.38-1.57), cardiac tamponade (aOR: 0.75, 95% CI: 0.17-3.36), vascular complications (aOR: 0.33, 95% CI: 0.09-1.22), cardiogenic shock (aOR: 1.77, 95% CI: 0.93-3.38), paravalvular leak (aOR: 0.55, 95% CI: 0.26-1.14), need for mechanical circulatory support device, and permanent pacemaker implantation (PPM) (aOR: 1.02, 95% CI: 0.69-1.52) were not significantly different between TAVI for BAV versus TAV. At 30- and 180-day follow-up duration, the risk of stroke and major postprocedural complications remained similar, except that TAVI in BAV had a higher incidence of PPM implantation compared with TAV. The yearly trend showed an increase in the utilization of TAVI for both TAV and BAV and a steady decline in the overall annual rate of in-hospital complications. CONCLUSION: TAVI utilization in patients with BAV has increased over the recent years. The relative odds of in-hospital mortality, and all other major complications, were similar between patients undergoing TAVI for BAV- and TAV-related AS.
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Estenose da Valva Aórtica , Doença da Válvula Aórtica Bicúspide , Doenças das Valvas Cardíacas , Acidente Vascular Cerebral , Substituição da Valva Aórtica Transcateter , Humanos , Pacientes Internados , Readmissão do Paciente , Doenças das Valvas Cardíacas/diagnóstico por imagem , Doenças das Valvas Cardíacas/cirurgia , Doenças das Valvas Cardíacas/etiologia , Resultado do Tratamento , Estenose da Valva Aórtica/diagnóstico por imagem , Estenose da Valva Aórtica/cirurgia , Estenose da Valva Aórtica/etiologia , Valva Aórtica/diagnóstico por imagem , Valva Aórtica/cirurgia , Acidente Vascular Cerebral/etiologiaRESUMO
BACKGROUND: Large-for-gestational-age fetuses are at increased risk of perinatal morbidity and mortality. Magnetic resonance imaging seems to be more accurate than ultrasound in the prediction of macrosomia; however, there is no well-powered study comparing magnetic resonance imaging with ultrasound in routine pregnancies. OBJECTIVE: This study aimed to prospectively compare estimates of fetal weight based on 2-dimensional ultrasound and magnetic resonance imaging with actual birthweights in routine pregnancies. STUDY DESIGN: From May 2016 to February 2019, women received counseling at the 36-week clinic. Written informed consent was obtained for this Ethics Committee-approved study. In this prospective, single-center, blinded study, pregnant women with singleton pregnancies between 36 0/7 and 36 6/7 weeks' gestation underwent both standard evaluation of estimated fetal weight with ultrasound according to Hadlock et al and magnetic resonance imaging according to the formula developed by Baker et al, based on the measurement of the fetal body volume. Participants and clinicians were aware of the results of the ultrasound but blinded to the magnetic resonance imaging estimates. Birthweight percentile was considered as the gold standard for the ultrasound and magnetic resonance imaging-derived percentiles. The primary outcome was the area under the receiver operating characteristic curve for the prediction of large-for-gestation-age neonates with birthweights of ≥95th percentile. Secondary outcomes included the comparative prediction of large-for-gestation-age neonates with birthweights of ≥90th, 97th, and 99th percentiles and small-for-gestational-age neonates with birthweights of ≤10th, 5th, and 3rd percentiles for gestational age and maternal and perinatal complications. RESULTS: Of 2914 women who were initially approached, results from 2378 were available for analysis. Total fetal body volume measurements were possible for all fetuses, and the time required to perform the planimetric measurements by magnetic resonance imaging was 3.0 minutes (range, 1.3-5.6). The area under the receiver operating characteristic curve for the prediction of a birthweight of ≥95th percentile was 0.985 using prenatal magnetic resonance imaging and 0.900 using ultrasound (difference=0.085, P<.001; standard error, 0.020). For a fixed false-positive rate of 5%, magnetic resonance imaging for the estimation of fetal weight detected 80.0% (71.1-87.2) of birthweight of ≥95th percentile, whereas ultrasound for the estimation of fetal weight detected 59.1% (49.0-68.5) of birthweight of ≥95th percentile. The positive predictive value was 42.6% (37.8-47.7) for the estimation of fetal weight using magnetic resonance imaging and 35.4% (30.1-41.1) for the estimation of fetal weight using ultrasound, and the negative predictive value was 99.0% (98.6-99.3) for the estimation of fetal weight using magnetic resonance imaging and 98.0% (97.6-98.4) for the estimation of fetal weight using ultrasound. For a fixed false-positive rate of 10%, magnetic resonance imaging for the estimation of fetal weight detected 92.4% (85.5-96.7) of birthweight of ≥95th percentile, whereas ultrasound for the estimation of fetal weight detected 76.2% (66.9-84.0) of birthweight of ≥95th percentile. The positive predictive value was 29.9% (27.2-32.8) for the estimation of fetal weight using magnetic resonance imaging and 26.2% (23.2-29.4) for the estimation of fetal weight using ultrasound, and the negative predictive value was 99.6 (99.2-99.8) for the estimation of fetal weight using magnetic resonance imaging and 98.8 (98.4-99.2) for the estimation of fetal weight using ultrasound. The area under the receiver operating characteristic curves for the prediction of large-for-gestational-age neonates with birthweights of ≥90th, 97th, and 99th percentiles and small-for-gestational-age neonates with birthweights of ≤10th, 5th, and 3rd percentiles was significantly larger in prenatal magnetic resonance imaging than in ultrasound (P<.05 for all). CONCLUSION: At 36 weeks' gestation, magnetic resonance imaging for the estimation of fetal weight performed significantly better than ultrasound for the estimation of fetal weight in the prediction of large-for-gestational-age neonates with birthweights of ≥95th percentile for gestational age and all other recognized cutoffs for large-for-gestational-age and small-for-gestational-age neonates (P<.05 for all).
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Macrossomia Fetal/diagnóstico por imagem , Feto/diagnóstico por imagem , Imageamento por Ressonância Magnética , Diagnóstico Pré-Natal , Adulto , Peso ao Nascer , Feminino , Humanos , Gravidez , Terceiro Trimestre da Gravidez , Estudos ProspectivosRESUMO
Breast cancer has been one of the most challenging women's cancers and leading cause of mortality for decades. There are several studies being conducted all the time to find a cure for breast cancer. Quinoline derivatives have shown their potential as antitumor agents in breast cancer therapy. In this work, three-dimensional quantitative structure-activity relationships (3D-QSAR) and molecular docking with aromatase enzyme (Protein Data Bank: 3S7S) studies were performed to suggest the current scenario of quinoline derivatives as antitumor agents and to refine the path of these derivatives to discover and develop new drugs against breast cancer. For developing the 3D-QSAR model, comparative molecular similarity indices analysis (CoMSIA) and comparative molecular field analysis (CoMFA) were included. To attain the high level of predictability, the best CoMSIA model was applied. External validation utilizing a test set has been used in order to validate the predictive capabilities of the built model. According to the findings, electrostatic, hydrophobic and hydrogen bond donor, and acceptor fields had a significant impact on antibreast cancer activity. Thus, we generated a variety of novel effective aromatase inhibitors based on prior findings and we predicted their inhibitory activity using the built model. In addition, absorption, distribution, metabolism, elimination and toxicity properties were employed to explore the effectiveness of new drug candidates.
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Antineoplásicos , Neoplasias da Mama , Antineoplásicos/química , Antineoplásicos/farmacologia , Aromatase , Inibidores da Aromatase/farmacologia , Neoplasias da Mama/tratamento farmacológico , Desenho de Fármacos , Feminino , Humanos , Modelos Moleculares , Simulação de Acoplamento Molecular , Relação Quantitativa Estrutura-AtividadeRESUMO
Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a pandemic that impacted the lives of billions of people worldwide. Angiotensin-converting enzyme 2 (ACE2) receptor act as a gate for viral cell entry through binding to virus S-protein. Cardiovascular patients are thought to be more susceptible to severe COVID-19 infection due to overexpression of ACE2 receptors in these patients. There is a growing body of evidence suggesting worse outcomes and increased mortality among COVID-19 patients with preexisting cardiovascular diseases. SARS-CoV-2 is capable of causing a wide range of cardiovascular diseases including myocarditis, heart failure, arrhythmia, myocardial ischemia and venous thromboembolism. Drug-disease interaction in COVID-19 patients with preexisting cardiovascular conditions has become a major concern. In this review, we discuss different aspects of the relationship between COVID-19 and the cardiovascular system along with a brief pharmacological overview.
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COVID-19 , Doenças Cardiovasculares , Enzima de Conversão de Angiotensina 2 , Humanos , Peptidil Dipeptidase A/metabolismo , SARS-CoV-2RESUMO
The impact of COVID-19 was felt across the globe when it first emerged in December 2019. However, within a year, there was a new hope with the development and approval of mRNA vaccines. The Comirnaty and Pfizer-BioNTech BNT162b2 mRNA vaccine showed an efficacy of 95 percent in preventing COVID-19 disease. However, subsequent studies conducted on immunocompromised hosts showed the efficacy to be significantly lower than the initial reported 95 percent, making these patients prone to COVID-19 disease despite the initially recommended two doses. On Sept. 22, 2021, a third dose was approved for immunocompromised hosts. In this article, we report the case of a 67-year-old female with overlap connective tissue disease on mycophenolate mofetil who had a prolonged hospital course because of severe COVID-19 disease complicated by pulmonary embolism despite receiving three doses of the BNT162b2 mRNA vaccine.
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COVID-19 , Idoso , Vacina BNT162 , Vacinas contra COVID-19 , Feminino , Humanos , Vacinação , Vacinas Sintéticas , Vacinas de mRNARESUMO
BACKGROUND: Coronavirus disease 2019 (COVID-19) has become a leading cause of morbidity and mortality worldwide. One of the major complications of COVID-19 infection is the hypercoagulability state. Cardiac thrombi and venous thromboembolism (VTE) have been documented with severe COVID-19 infection. We present a case of large right atrial (RA) thrombus in transit incidentally diagnosed following a mild COVID-19 in a previously vaccinated patient. CASE SUMMARY: An 85-year-old male presented to the emergency department two weeks following resolution of a mild COVID-19 infection due to an incidentally discovered large RA thrombus. Computed tomography with angiography of the chest was positive for acute pulmonary thromboembolic disease with large clot burden and findings consistent with right heart strain. The patient remained hemodynamically stable and was successfully managed with anticoagulation. CONCLUSION: RA thrombi and VTE can occur in patients with mild COVID-19 infection and in the setting of full COVID-19 vaccination. Echocardiography is a useful imaging modality in this patient population.
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COVID-19 , Cardiopatias , Trombose , Tromboembolia Venosa , Idoso de 80 Anos ou mais , COVID-19/complicações , Vacinas contra COVID-19 , Cardiopatias/diagnóstico por imagem , Cardiopatias/etiologia , Humanos , Masculino , Trombose/diagnóstico por imagem , Trombose/etiologiaRESUMO
AIMS: The Food and Drug Administration (FDA) approval of the Watchman device [percutaneous left atrial appendage occlusion (LAAO)] has resulted in the widespread use of this procedure in many centres across the USA. We sought to estimate the nationwide utilization and frequency of adverse outcomes associated with Watchman device implantation. The objective of this study was to evaluate the Watchman device implantation peri-procedural complications and comparison of the results with the previous studies. METHODS AND RESULTS: The National Inpatient Sample (NIS) was queried for all hospitalizations with a primary diagnosis of atrial fibrillation or atrial flutter during the year 2016 with percutaneous LAAO during the same admission (ICD-10 code-02L73DK). The frequency of peri-procedural complications, including mortality, procedure-related stroke, major bleeding requiring blood transfusion, and pericardial effusion, was assessed. We compared the complication rates with the published randomized controlled trials and the European Watchman registry. An estimated 5175 LAAO procedures were performed in 2016. The majority of procedures was performed in males (59.1%), age ≥75 years (58.7%), and White (83.1%). The overall complication rate was 1.9%. The in-hospital mortality was 0.29%. Pericardial effusion requiring pericardiocentesis was the most frequent complication (0.68%). Bleeding requiring transfusion was noted in 0.1% of device implants. The rates of post-procedure stroke and systemic embolism were 0% and 0.29%, respectively. CONCLUSION: Percutaneous LAAO with the Watchman device in the USA is associated with low in-hospital complications and a similar safety profile to a recently published EWOLUTION cohort. The complication rates were lower than those reported in the major randomized clinical trials (RCTs). We report the frequency of peri-procedural complications of the LAAO using the Watchman device from the NIS database. We also compare the frequency of peri-procedural complications with the previously published RCTs and EWOLUTION cohort. Our findings are in concordance with findings from EWOLUTION cohort and compare favourably with RCTs.
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Apêndice Atrial , Fibrilação Atrial , Acidente Vascular Cerebral , Idoso , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/cirurgia , Hemorragia , Humanos , Masculino , Resultado do TratamentoRESUMO
BACKGROUND: The risk of endocarditis varies with CHD complexity and the presence of prosthetic valves. The purpose of the study was therefore to describe incidence and outcomes of prosthetic valve endocarditis in adults with repair tetralogy of Fallot. METHODS: Retrospective review of adult tetralogy of Fallot patients who underwent prosthetic valve implantation, 1990-2017. We defined prosthetic valve endocarditis-related complications as prosthetic valve dysfunction, perivalvular extension of infection such abscess/aneurysm/fistula, heart block, pulmonary/systemic embolic events, recurrent endocarditis, and death due to sepsis. RESULTS: A total of 338 patients (age: 37 ± 15 years) received 352 prosthetic valves (pulmonary [n = 308, 88%], tricuspid [n = 13, 4%], mitral [n = 9, 3%], and aortic position [n = 22, 6%]). The annual incidence of prosthetic valve endocarditis was 0.4%. There were 12 prosthetic valve endocarditis-related complications in six patients, and these complications were prosthetic valve dysfunction (n = 4), systemic/pulmonary embolic events (n = 2), heart block (n = 1), aortic root abscess (n = 1), recurrent endocarditis (n = 2), and death due to sepsis (n = 1). Three (50%) patients required surgery at 2 days, 6 weeks, and 23 weeks from the time of prosthetic valve endocarditis diagnosis. Altogether three of the six (50%) patients died, and one of these deaths was due to sepsis. CONCLUSIONS: The incidence, complication rate, and outcomes of prosthetic valve endocarditis in tetralogy of Fallot patients underscore some of the risks of having a prosthetic valve. It is important to educate the patients on the need for early presentation if they develop systemic symptoms, have a high index of suspicion for prosthetic valve endocarditis, and adopt a multi-disciplinary care approach in this high-risk population.
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Endocardite Bacteriana/epidemiologia , Próteses Valvulares Cardíacas/efeitos adversos , Infecções Relacionadas à Prótese/epidemiologia , Sepse/mortalidade , Tetralogia de Fallot/cirurgia , Adulto , Endocardite Bacteriana/etiologia , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Minnesota/epidemiologia , Infecções Relacionadas à Prótese/etiologia , Estudos Retrospectivos , Fatores de Risco , Sepse/etiologia , Adulto JovemRESUMO
BACKGROUND: Atrial arrhythmia is a late complication after tetralogy of Fallot (TOF) repair, but arrhythmia outcomes data are limited. OBJECTIVES: The purpose of the study was to describe atrial arrhythmia presentations, outcomes of antiarrhythmic therapy, and impact of arrhythmia on transplant-free survival. METHODS: We reviewed the MACHD (Mayo Adult Congenital Heart Disease) Registry and identified 113 patients (age 49⯱â¯13 years) with documented arrhythmia, and 302 patients without history of arrhythmia, 1990-2017. We classified arrhythmias into atrial fibrillation and atrial flutter/tachycardia based on the rhythm on the first abnormal electrocardiogram. RESULTS: At the time of first documented arrhythmia, 58(51%) had atrial fibrillation while 55(49%) had atrial flutter/tachycardia. Of the 113 patients, 14(12%) received rhythm control with class I/III antiarrhythmic drugs (AAD), 79(70%) had direct current cardioversion, 9(8%) received rate control with class II/IV AAD, and 11(10%) received only anticoagulation. Successful cardioversion occurred in 100(89%) patients, and arrhythmia recurrence rate was 16 per 100 patient-years. The multivariate risk factors for death and/or heart transplant were atrial fibrillation (HR 1.94, CI 1.10-3.15, Pâ¯=â¯.031) and older age (HR 1.63, CI 1.12-2.43, Pâ¯=â¯.019) per 5 year increment. CONCLUSIONS: Atrial fibrillation, but not atrial flutter, was associated with reduced survival in our repaired TOF cohort. Further studies are required to determine if more aggressive antiarrhythmic therapy will improve survival in patients with atrial fibrillation.
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Fibrilação Atrial/mortalidade , Flutter Atrial/mortalidade , Complicações Pós-Operatórias/mortalidade , Tetralogia de Fallot/cirurgia , Adulto , Fatores Etários , Antiarrítmicos/uso terapêutico , Fibrilação Atrial/terapia , Flutter Atrial/terapia , Ablação por Cateter/estatística & dados numéricos , Cardioversão Elétrica/métodos , Cardioversão Elétrica/estatística & dados numéricos , Feminino , Transplante de Coração/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/terapia , Recidiva , Sistema de Registros , Estudos Retrospectivos , Fatores de Risco , Taquicardia/mortalidade , Taquicardia/terapia , Tetralogia de Fallot/mortalidade , Resultado do TratamentoRESUMO
Fetuses at the extremes of growth abnormalities carry a risk of perinatal morbidity and death. Their identification traditionally is done by 2-dimensional ultrasound imaging, the performance of which is not always optimal. Magnetic resonance imaging superbly depicts fetal anatomy and anomalies and has contributed largely to the evaluation of high-risk pregnancies. In 1994, magnetic resonance imaging was introduced for the estimation of fetal weight, which is done by measuring the fetal body volume and converting it through a formula to fetal weight. Approximately 10 studies have shown that magnetic resonance imaging is more accurate than 2-dimensional ultrasound imaging in the estimation of fetal weight. Yet, despite its promise, the magnetic resonance imaging technique currently is not implemented clinically. Over the last 5 years, this technique has evolved quite rapidly. Here, we review the literature data, provide details of the various measurement techniques and formulas, consider the application of the magnetic resonance imaging technique in specific populations such as patients with diabetes mellitus and twin pregnancies, and conclude with what we believe could be the future perspectives and clinical application of this challenging technique. The estimation of fetal weight by ultrasound imaging is based mainly on an algorithm that takes into account the measurement of biparietal diameter, head circumference, abdominal circumference, and femur length. The estimation of fetal weight by magnetic resonance imaging is based on one of the 2 formulas: (1) magnetic resonance imaging-the estimation of fetal weight (in kilograms)=1.031×fetal body volume (in liters)+0.12 or (2) magnetic resonance imaging-the estimation of fetal weight (in grams)=1.2083×fetal body volume (in milliliters)Ë0.9815. Comparison of these 2 formulas for the detection of large-for-gestational age neonates showed similar performance for preterm (P=.479) and for term fetuses (P=1.000). Literature data show that the estimation of fetal weight with magnetic resonance imaging carries a mean or median relative error of 2.6 up to 3.7% when measurements were performed at <1 week from delivery; whereas for the same fetuses, the relative error at 2-dimensional ultrasound imaging varied between 6.3% and 11.4%. Further, in a series of 270 fetuses who were evaluated within 48 hours from birth and for a fixed false-positive rate of 10%, magnetic resonance imaging detected 98% of large-for-gestational age neonates (≥95th percentile for gestation) compared with 67% with ultrasound imaging estimates. For the same series, magnetic resonance imaging applied to the detection of small-for-gestational age neonates ≤10th percentile for gestation, for a fixed 10% false-positive rate, reached a detection rate of 100%, compared with only 78% for ultrasound imaging. Planimetric measurement has been 1 of the main limitations of magnetic resonance imaging for the estimation of fetal weight. Software programs that allow semiautomatic segmentation of the fetus are available from imaging manufacturers or are self-developed. We have shown that all of them perform equally well for the prediction of large-for-gestational age neonates, with the advantage of the semiautomatic methods being less time-consuming. Although many challenges remain for this technique to be generalized, a 2-step strategy after the selection of a group who are at high risk of the extremes of growth abnormalities is the most likely scenario. Results of ongoing studies are awaited (ClinicalTrials.gov Identifier # NCT02713568).
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Peso ao Nascer , Peso Fetal , Feto/diagnóstico por imagem , Imageamento por Ressonância Magnética , Diabetes Gestacional , Feminino , Humanos , Imageamento Tridimensional , Conceitos Matemáticos , Gravidez , Gravidez de Gêmeos , Software , Ultrassonografia Pré-NatalAssuntos
Ablação por Cateter , Taquicardia Ventricular , Complexos Ventriculares Prematuros , Ablação por Cateter/efeitos adversos , Humanos , Valva Mitral/diagnóstico por imagem , Valva Mitral/cirurgia , Taquicardia Ventricular/diagnóstico , Taquicardia Ventricular/cirurgia , Complexos Ventriculares Prematuros/diagnóstico , Complexos Ventriculares Prematuros/cirurgiaRESUMO
Background and aim: Heart failure with preserved ejection fraction (HFpEF) is associated with an increased risk of heart failure (HF) hospitalizations and cardiovascular death (CVD). Both dapagliflozin and sacubitril-valsartan have recently shown convincing reductions in the combined risk of CVD and HF hospitalizations in patients with HF and mildly reduced ejection fraction (HFmrEF) or HFpEF. We aimed to investigate the cost-per-outcome implications of dapagliflozin vs sacubitril-valsartan in the treatment of HFmrEF or HFpEF patients. Methods: We compared the annualized cost needed to treat (CNT) to prevent the composite outcome of total HF hospitalizations and CVD with dapagliflozin or sacubitril-valsartan. The CNT was estimated by multiplying the annualized number needed to treat (aNNT) by the annual cost of therapy. The aNNT was calculated based on data collected from the DELIVER trial for dapagliflozin and a pooled analysis of the PARAGLIDE-HF and PARAGON-HF trials for sacubitril-valsartan. Costs were based on 2022 US prices. Scenario analyses were performed to attenuate the differences in the studies' populations. Results: The aNNT with dapagliflozin in DELIVER was 30 (95% confidence interval [CI]: 21-62) versus 44 (95% CI: 25-311) with sacubitril-valsartan in a pooled analysis of PARAGLIDE-HF and PARAGON-HF, with an annual cost of $4,951 and $5,576, respectively. The corresponding CNTs were $148,547.13 (95% CI: $103,982.99-$306,997.39) for dapagliflozin and $245,346.77 (95% CI: $139,401.58-1,734,155.60) for sacubitril-valsartan for preventing the composite outcome of CVD and HF hospitalizations. The CNT for preventing all-cause mortality was lower for dapagliflozin than sacubitril-valsartan $1,128,958.15 [CI: $401,077.24-∞] vs $2,185,816.71 [CI: $607,790.87-∞]. Conclusion: Dapagliflozin provides a better monetary value than sacubitril-valsartan in preventing the composite outcome of total HF hospitalizations and CVD among patients with HFmrEF or HFpEF.
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Due to the rising human population and industrialization, harmful chemical compounds such as 4-nitrophenol (4-NP) and various dyes are increasingly released into the environment, resulting in water pollution. It is essential to convert these harmful chemicals into harmless compounds to mitigate this pollution. This research focuses on synthesizing a novel heterogeneous catalyst using modified canvas fabric (CF) decorated with silver metal nanoparticles on graphene oxide nanosheets (Ag-GO/CF). The process involves coating the fabrics (CF) with graphene oxide (GO) nanosheets through sonication. Subsequently, silver nanoparticles are deposited in situ and reduced on the GO surface, resulting in the formation of the Ag-GO/CF composite. Various physicochemical characterizations were conducted to examine the interfacial interactions between CF, GO, and Ag nanoparticles. The catalytic activity of the nanocomposite was assessed by hydrogenating 4-nitrophenol (4-NP) to 4-aminophenol (4-AP) in the presence of sodium borohydride (NaBH4). The results showed that the 10%Ag-5%GO/CF with a surface of 6 cm2 (3 × 2 cm) exhibited the highest catalytic activity, achieving a reduction efficiency of over 96% in 5 min. The 4-NP reduction reaction rate was well-fitted with a pseudo-first-order kinetics model with an apparent reaction rate constant (Kapp) of 0.676 min-1. Furthermore, the Ag-GO/CF composite demonstrated remarkable stability over successive cycles, with no noticeable decrease in its catalytic activity, suggesting its promising application for long-term chemical catalytic processes. This synthesized composite can be easily added to and removed from the reaction solution while maintaining high catalytic performance in the reduction of 4-NP, and it could be beneficial in avoiding problems related to powder separation.
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Cervical cancer is a major health problem of women. Hormone therapy, via aromatase inhibition, has been proposed as a promising way of blocking estrogen production as well as treating the progression of estrogen-dependent cancer. To overcome the challenging complexities of costly drug design, in-silico strategy, integrating Structure-Based Drug Design (SBDD) and Ligand-Based Drug Design (LBDD), was applied to large representative databases of 39 quinazoline and thioquinazolinone compound derivatives. Quantum chemical and physicochemical descriptors have been investigated using density functional theory (DFT) and MM2 force fields, respectively, to develop 2D-QSAR models, while CoMSIA and CoMFA descriptors were used to build 3D-QSAR models. The robustness and predictive power of the reliable models were verified, via several validation methods, leading to the design of 6 new drug-candidates. Afterwards, 2 ligands were carefully selected using virtual screening methods, taking into account the applicability domain, synthetic accessibility, and Lipinski's criteria. Molecular docking and pharmacophore modelling studies were performed to examine potential interactions with aromatase (PDB ID: 3EQM). Finally, the ADMET properties were investigated in order to select potential drug-candidates against cervical cancer for experimental in vitro and in vivo testing.