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AIMS: Dopamine beta-hydroxylase (DßH) inhibitors, like zamicastat, hold promise for treating pulmonary arterial hypertension. This study aimed to validate the mechanism of action of zamicastat by studying its effect on the overdrive of the sympathetic nervous system (SNS). METHODS: A single-centre, prospective, double-blind, randomized, placebo-controlled, crossover study evaluated the effect of 400 mg zamicastat in 22 healthy male subjects. Cold pressor test (CPT) was performed at screening and each treatment period on Days -1 and 10. Plasma and 24 h-urine levels of dopamine (DA), epinephrine (EPI) and norepinephrine (NE), and plasma DßH activity, were measured. RESULTS: Compared to placebo, zamicastat showed a - 4.62 mmHg decrease in systolic blood pressure during the cold stimulus vs. rest phases on Day 10 of CPT (P = .020). Zamicastat decreased mean arterial pressure response to cold stimulus during CPT (-2.62 mmHg; P = .025). At Day 10, zamicastat significantly increased plasma DA, before CPT (12.63 ng/L; P = .040) and after CPT (19.22 ng/L; P = .001) as well as the estimated plasma EPI change from baseline after CPT (P = .040). Inhibition of plasma DßH activity ranged from 19.8% to 25.0%. At Day 10, significant reductions in 24-h urinary excretion of EPI (P = .002) and NE (P = .001) were observed. Zamicastat Cτ geometric mean ± GSD ranged from 45.86 ± 1.46 ng/mL on Day 3 to 58.64 ± 1.52 ng/mL on Day 10, with moderate inter-individual variability (CV: 32.6%-36.6%). Steady state was already achieved on Day 6. CONCLUSIONS: Our results demonstrated the effect of zamicastat on the overdrive sympathetic response to cold stimulus, confirming its potential as SNS modulator.
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INTRODUCTION: Cytisinicline is a nicotinic acetylcholine receptor partial agonist marketed historically as oral tablets in Central and Eastern Europe as an aid to smoking cessation. Dosing and scheduled regimen for cytisinicline treatment is currently being redeveloped for market approval in the United States and elsewhere. AIMS AND METHODS: A phase 1, double-blind, randomized, placebo-controlled, single-ascending dose clinical trial was conducted under fasting conditions in healthy adults who were current daily (>10 cigarettes) smokers. Safety parameters for the identification of a maximum tolerated dose (MTD) and limited supportive pharmacokinetic assessments were evaluated. Ascending single oral doses of cytisinicline or placebo were administered to 9 cohorts, each comprised of eight unique participants (randomization: 6 cytisinicline; 2 placebo). Dose escalation to the next cohort was dependent upon the safety review of preceding cohorts. Dose levels tested were 6, 9, 12, 15, 18, 21, 24, 27, and 30 mg. Treatment-emergent adverse events (TEAEs) and clinically relevant changes in laboratory blood tests, vital signs, and 12-lead electrocardiograms were evaluated. RESULTS: Seventy-two participants completed the study (54 cytisinicline; 18 placebo). Nausea was the most common TEAE (10 participants [19%]). The MTD was defined as cytisinicline 30 mg based on gastrointestinal symptoms, predominantly vomiting (2 of 6 subjects, 33%). Maximum plasma concentration (observed Cmax) values appeared to plateau at higher dose levels (beyond 24 mg). CONCLUSIONS: Single cytisinicline doses up to 30 mg were well tolerated and raised no new safety concerns in fasting adult smokers. An increased frequency of gastrointestinal symptoms defined the MTD at 30 mg. IMPLICATIONS: The cytisinicline therapeutic dose being evaluated in phase 3 clinical trials is 3 mg, which is a 10-fold lower dose than the 30 mg MTD level for cytisinicline, resulting in an excellent safety margin.
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Fumantes , Adulto , Humanos , Europa Oriental , Método Duplo-Cego , Relação Dose-Resposta a DrogaRESUMO
Patients with cardiac pathology alone are already complex, when this is associated with oncologic pathology, or it's mere suspicion, the patient becomes even more complex. We present a clinical case of a patient with severe aortic stenosis with suspected cancer disease, whose diagnostic study could not be performed due to the patient's clinical condition. The option to intervene surgically was widely debated, never being a consensus among surgeons. There are many doubts about a clinical case of this type, and it is not easy to make a decision to operate. In case of doubt, the decision must always be in favor of the patient: in dubio pro malum.
Se os doentes com patologia cardíaca, por si só, já são doentes complexos, quando a esta se associa patologia oncológica, ou a sua mera suspeição, o doente torna-se ainda mais complexo. Apresentamos um caso clínico de um doente com estenose aórtica severa, com suspeita de doença oncológica, cujo estudo diagnóstico não se poderia realizar devido ao facto de o estado clínico do doente não permitir tolerar o mesmo. A opção de intervir cirurgicamente foi uma opção amplamente debatida, nunca se encontrando um consenso entre os cirurgiões. São imensas as dúvidas levantadas perante um quadro clínico deste tipo, não sendo fácil a tomada de decisão de operar. Em caso de dúvida, a decisão deve ser sempre a favor do doente: in dubio pro malum.
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Estenose da Valva Aórtica/cirurgia , Tomada de Decisão Clínica , Neoplasias/complicações , Neoplasias/diagnóstico , Estenose da Valva Aórtica/complicações , Consenso , HumanosRESUMO
Cytochrome P450 (CYP) 3A4 is an enzyme involved in the metabolism of many drugs that are currently on the market and is therefore a key player in drug-drug interactions (DDIs). ACT-1004-1239 is a potent and selective, first-in-class ACKR3/CXRC7 antagonist being developed as a treatment for demyelinating diseases including multiple sclerosis. Based on the human absorption, distribution, metabolism, and excretion (ADME) study results, ACT-1004-1239 is predominantly metabolized by CYP3A4. This study investigated the effect of the strong CYP3A4 inhibitor, itraconazole, on the pharmacokinetics of single-dose ACT-1004-1239 in healthy male subjects. In the open-label, fixed-sequence DDI study, a total of 16 subjects were treated. Each subject received a single dose of 10 mg ACT-1004-1239 (Treatment A) in the first period followed by concomitant administration of multiple doses of 200 mg itraconazole and a single dose of 10 mg ACT-1004-1239 in the second period. We report a median of difference in tmax (90% confidence interval, CI) of 0.5 h (0.0, 1.0) comparing both treatments. The geometric mean ratio (GMR) (90% CI) of Cmax and AUC0-∞ was 2.16 (1.89, 2.47) and 2.77 (2.55, 3.00), respectively. The GMR (90% CI) of t1/2 was 1.46 (1.26, 1.70). Both treatments were well-tolerated with an identical incidence in subjects reporting treatment-emergent adverse events (TEAE). The most frequently reported TEAEs were headache and nausea. In conclusion, ACT-1004-1239 is classified as a moderately sensitive CYP3A4 substrate (i.e., increase of AUC ≥2- to <5-fold), and this should be considered in further clinical studies if CYP3A4 inhibitors are concomitantly administered.
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Inibidores do Citocromo P-450 CYP3A , Citocromo P-450 CYP3A , Interações Medicamentosas , Itraconazol , Humanos , Masculino , Itraconazol/farmacocinética , Itraconazol/administração & dosagem , Itraconazol/farmacologia , Adulto , Inibidores do Citocromo P-450 CYP3A/farmacocinética , Inibidores do Citocromo P-450 CYP3A/administração & dosagem , Inibidores do Citocromo P-450 CYP3A/farmacologia , Adulto Jovem , Citocromo P-450 CYP3A/metabolismo , Pessoa de Meia-Idade , Voluntários Saudáveis , Área Sob a CurvaRESUMO
This study intended to evaluate the interactions between zamicastat and epoprostenol in healthy human subjects. This was a single-center, open-label, two-period study. In period 1, epoprostenol 8 ng/kg/min was administered alone. In period 2, epoprostenol 8 ng/kg/min was administered following an 8-day treatment with zamicastat. Since the initial dose of epoprostenol showed to be insufficiently tolerated, it was decreased to 6 ng/kg/min. Blood samples were collected to determine the metabolites of epoprostenol and concentrations of zamicastat and its metabolites. A total of 54 subjects were enrolled and data from 28 subjects were available for pharmacokinetic analysis. The epoprostenol plus zamicastat-to-epoprostenol geometric means ratio (GMR) and corresponding 90% confidence interval (CI) for Cav,ss and area under the plasma concentration-time curve from time 0 up to 16 h at steady state (AUC0-16,ss) of the metabolites of epoprostenol were within the acceptance bioequivalence range (80.00%-125.00%). The intrasubject coefficient of variation (ISCV) was below 10% for both parameters, on both metabolites. For zamicastat AUC0-τ,ss, the zamicastat plus epoprostenol-to-zamicastat GMR and corresponding 90% CI were within the bioequivalence acceptance range, while for zamicastat Cmax,ss, the lower limit of the 90% CI was slightly below the acceptance range. For zamicastat metabolites, Cmax,ss and AUC0-τ,ss and the zamicastat plus epoprostenol-to-zamicastat GMR were below the acceptance bioequivalence range. ISCV was between 30% and 41% for Cmax,ss and between 21% and 41% for AUC0-τ,ss, for zamicastat and both metabolites. This study showed that the administration of zamicastat did not significantly modify the cardiovascular effects of epoprostenol and that the interactions between zamicastat and epoprostenol are not expected to be clinically relevant.
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OBJECTIVE: To evaluate the prevalence of ultra-processed food consumption and associated factors among children enrolled in the public school system of the city of Barbacena, Minas Gerais, Brazil. METHODS: This is a cross-sectional study conducted with schoolchildren aged 7-9 years, of both sexes, enrolled in state public schools. Food intake was assessed using the Previous Day Food Questionnaire and the level of physical activity by the Previous Day Physical Activity Questionnaire. The listed foods were classified according to the extent and purpose of industrial processing, using the NOVA classification. Pearson's χ2 test, Fisher's exact test, χ2 with Yates correction, and Poisson regression were used in the statistical analysis, estimating the crude and adjusted prevalence ratio, with 95% confidence intervals. RESULTS: The prevalence of daily ultra-processed food consumption was 69.6%. After adjusted analyses, the consumption of ultra-processed food was associated with the omission of breakfast, mid-afternoon snack, supper, low physical activity, and consumption of risk foods. On the other hand, consumption of in natura or minimally processed foods was associated with older age, the consumption of lunch, mid-afternoon snack, dinner, and protective foods. CONCLUSIONS: There is a high prevalence of ultra-processed foods consumption, associated with unhealthy dietary habits among schoolchildren. This highlights the need for nutritional counseling and educational actions, favoring healthy eating in childhood.
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Fast Foods , Alimento Processado , Masculino , Feminino , Humanos , Criança , Brasil/epidemiologia , Estudos Transversais , Comportamento Alimentar/psicologia , Manipulação de Alimentos , Dieta , Ingestão de EnergiaRESUMO
Antagonism of the chemokine receptor CXCR7 has shown promising effects in diverse disease areas through modulation of its ligands, CXCL11 and CXCL12. Preclinical data of the first-in-class CXCR7 antagonist, ACT-1004-1239, showed efficacy in animal models of multiple sclerosis and acute lung injury. In healthy humans, single-dose administration of ACT-1004-1239 revealed a favorable clinical profile. Here, we report the target engagement of ACT-1004-1239 in healthy mice and humans after multiple doses using CXCL11 and CXCL12 as biomarkers. In addition, safety/tolerability, concentration-QTc relationship, and pharmacokinetics (PK) were assessed in a randomized, double-blind, placebo-controlled Phase 1 clinical study. Multiple-dose ACT-1004-1239 dose-dependently increased CXCL12 plasma concentration across the investigated dose range in mice and humans (mice: 1-100 mg/kg b.i.d.; humans: 30-200 mg o.d.) when compared to vehicle/placebo demonstrating target engagement. Mouse and human PK/PD models predicted that CXCL12 concentration approached a plateau within these dose ranges. In humans, ACT-1004-1239 was rapidly absorbed (tmax: 1.75-3.01 h) and the terminal t1/2 was approximately 19 h. Steady-state conditions were reached by Day 3 with an accumulation index of 1.2. Female subjects had overall higher exposure compared to males. Multiple-dose ACT-1004-1239 was well tolerated up to 200 mg once daily in humans. There was no evidence of ACT-1004-1239-mediated QTc interval prolongation. Overall, multiple oral doses of ACT-1004-1239 showed target engagement with CXCR7 in healthy mice and humans, therefore, assessment of CXCL12 as translational tool for further investigations in patients is warranted. Favorable safety/tolerability and PK profiles allow for further clinical development.
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Oxazóis/farmacologia , Piperidinas/farmacologia , Receptores CXCR/antagonistas & inibidores , Administração Oral , Animais , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Voluntários Saudáveis , Humanos , Síndrome do QT Longo/induzido quimicamente , Masculino , Camundongos , Camundongos Endogâmicos DBA , Oxazóis/administração & dosagem , Piperidinas/administração & dosagem , Caracteres SexuaisRESUMO
OBJECTIVE: To evaluate the sociodemographic and lifestyle factors associated with abdominal obesity in children from public schools in Barbacena, state of Minas Gerais, Brazil. METHODS: This is a cross-sectional study conducted on 326 students aged 7 to 9 years from public schools in the urban area of the city. Anthropometric data included body weight, height, body mass index according to age, waist circumference, and waist-to-height ratio. Food consumption was evaluated using the Previous Day Food Questionnaire. Abdominal obesity was assessed based on waist circumference and waist-to-height ratio. The bivariate and multivariate analyses were performed by logistic regression, estimating the crude and adjusted odds ratio (OR), with 95% confidence interval. RESULTS: The prevalence of overweight was 30.7%; whereas the prevalence of abdominal obesity was 9.2 and 12.6% according to waist circumference and waist-to-height ratio, respectively. Boys (OR 2.76; 95%CI 1.22-6.25) and children from central schools (OR 2.73; 95%CI 1.08-6.80) presented an increased chance of abdominal obesity according to waist circumference. Abdominal obesity according to waist-to-height ratio was associated with the central location of the schools (OR 2.18; 95%CI 1.02-4.63) and the habit of skipping supper (OR 2.01; 95%CI 1.00-4.09). CONCLUSIONS: The findings showed that being a boy, studying in a central school, and skipping supper were the main risk factors associated with abdominal obesity.
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Obesidade Abdominal , Obesidade Infantil , Índice de Massa Corporal , Brasil/epidemiologia , Criança , Estudos Transversais , Humanos , Masculino , Obesidade Abdominal/epidemiologia , Obesidade Infantil/epidemiologia , Obesidade Infantil/etiologia , Prevalência , Fatores de Risco , Instituições Acadêmicas , Circunferência da CinturaRESUMO
Quality-by-Design (QbD) is a methodology used to build quality into products and is characterized by a well-defined roadmap. In this study, the application of Artificial Neural Networks (ANNs) in the QbD-based development of a test drug product is presented, where material specifications are defined and correlated with its performance in vivo. Along with other process parameters, drug particle size distribution (PSD) was identified as a critical material attribute and a three-tier specification was needed. An ANN was built with only five hidden nodes in one hidden layer, using hyperbolic tangent functions, and was validated using a random holdback of 33% of the dataset. The model led to significant and valid prediction formulas for the three responses, with R2 values higher than 0.94 for all responses, both for the training and the validation datasets. The prediction formulas were applied to contour plots and tight limits were set based on the design space and feasible working area for the drug PSD, as well as for process parameters. The manufacturing process was validated through the production of three exhibit batches of 180,000 tablets in the industrial GMP facility, and the ANN model was applied to successfully predict the in vitro dissolution, with a bias of approximately 5%. The product was then tested on two clinical studies (under fasting and fed conditions) and the criteria to demonstrate bioequivalence to the Reference Listed Drug were met. In this study, ANNs were successfully applied to support the establishment of drug specifications and limits for process parameters, bridging the formulation development with in vitro performance and the positive clinical results obtained in the bioequivalence studies.
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Química Farmacêutica/métodos , Composição de Medicamentos/métodos , Redes Neurais de Computação , Tamanho da Partícula , Controle de Qualidade , Solubilidade , Comprimidos/química , Equivalência TerapêuticaRESUMO
INTRODUCTION: Transcatheter aortic valve implantation (TAVI) is associated with cardiac electrical disturbances. However, beyond the risks of pacemaker implantation, few studies have performed a detailed assessment of the effects of TAVI on several cardiac electrical properties. OBJECTIVES: To assess the frequency and type of electrocardiographic disturbances following TAVI, according to the type of prostheses and to assess predictors of these disturbances. METHODS: We performed a detailed retrospective analysis of all electrocardiograms in patients who underwent TAVI, before and after the procedure, at a tertiary center from August 2007 to October 2016. Patients with permanent pacemakers were excluded. RESULTS: We included 182 patients (78±8 years; 56% female) and self-expanding prostheses (SEP) were implanted in 54%. Most patients (80%) were in sinus rhythm at baseline. After TAVI, 21% of patients developed new-onset atrial fibrillation and there was a significant increase in PR interval at discharge (186±41 ms vs. 176±32; p=0.003), which was not maintained after at six-month follow-up (181±35 ms, p=0.06). There was also a significant increase in QRS duration at discharge (129±28 ms vs. 114±25 at baseline p<0.0001), which persisted at six-months (122±28 ms, p<0.0001). New-onset left-bundle branch block (LBBB) was observed in 25% of patients. The depth of valve implantation was a predictor of new LBBB at discharge after multivariate analysis (OR 37.6, 95% CI 14.6-65.2, p=0.001). CONCLUSIONS: The main electrocardiographic disturbances post TAVI were PR prolongation, increased QRS and new-onset LBBB. These disturbances were more pronounced in patients undergoing SEP implantation and tended to improve at six-month follow-up. The depth of valve implantation was a predictor of conduction disturbances.
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Próteses Valvulares Cardíacas , Substituição da Valva Aórtica Transcateter , Valva Aórtica/cirurgia , Feminino , Humanos , Masculino , Estudos Retrospectivos , Substituição da Valva Aórtica Transcateter/efeitos adversos , Resultado do TratamentoRESUMO
The prevalence of transmitted human immunodeficiency virus type 1 drug resistance in Angola in 2001 in 196 untreated patients was investigated. All subtypes were detected, along with unclassifiable and complex recombinant strains. Numerous new polymorphisms were identified in the reverse transcriptase and protease. Two (1.6%) unrelated patients harbored nucleoside reverse transcriptase inhibitor- and nonnucleoside reverse transcriptase inhibitor-resistant viruses (mutations: M41L, D67N, M184V, L210W, T215Y or T215F, and K103N). Continued surveillance of drug resistance is required for maximization of ART efficacy in Angola.
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Fármacos Anti-HIV/uso terapêutico , Farmacorresistência Viral/genética , Infecções por HIV/virologia , HIV-1/efeitos dos fármacos , HIV-1/genética , Inibidores da Transcriptase Reversa/farmacologia , Adulto , Angola/epidemiologia , Feminino , Variação Genética , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Humanos , Masculino , Mutação/genética , Peptídeo Hidrolases/genética , DNA Polimerase Dirigida por RNA/genética , Inibidores da Transcriptase Reversa/uso terapêutico , Adulto JovemRESUMO
Functional tricuspid regurgitation is a prevalent disease, especially among patients with other valve disorders, and is associated with significant morbidity and mortality. Its management is challenging, and many patients deemed at high surgical risk are managed conservatively. Despite optimization of pharmacological treatment, many patients continue to be symptomatic, thus leading to interest in percutaneous interventional techniques. The Mitralign system has recently been used for the treatment of functional tricuspid regurgitation, with favorable clinical and imaging results. We report the first case in Portugal to our knowledge of percutaneous tricuspid regurgitation treatment with the Mitralign system.
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Insuficiência da Valva Tricúspide/cirurgia , Idoso , Procedimentos Cirúrgicos Cardíacos/instrumentação , Procedimentos Cirúrgicos Cardíacos/métodos , Feminino , HumanosRESUMO
Abstract Objective: To evaluate the prevalence of ultra-processed food consumption and associated factors among children enrolled in the public school system of the city of Barbacena, Minas Gerais, Brazil. Methods: This is a cross-sectional study conducted with schoolchildren aged 7-9 years, of both sexes, enrolled in state public schools. Food intake was assessed using the Previous Day Food Questionnaire and the level of physical activity by the Previous Day Physical Activity Questionnaire. The listed foods were classified according to the extent and purpose of industrial processing, using the NOVA classification. Pearson's χ2 test, Fisher's exact test, χ2 with Yates correction, and Poisson regression were used in the statistical analysis, estimating the crude and adjusted prevalence ratio, with 95% confidence intervals. Results: The prevalence of daily ultra-processed food consumption was 69.6%. After adjusted analyses, the consumption of ultra-processed food was associated with the omission of breakfast, mid-afternoon snack, supper, low physical activity, and consumption of risk foods. On the other hand, consumption of in natura or minimally processed foods was associated with older age, the consumption of lunch, mid-afternoon snack, dinner, and protective foods. Conclusions: There is a high prevalence of ultra-processed foods consumption, associated with unhealthy dietary habits among schoolchildren. This highlights the need for nutritional counseling and educational actions, favoring healthy eating in childhood.
RESUMO Objetivo Avaliar a prevalência de consumo de alimentos ultraprocessados e fatores associados em crianças matriculadas na rede pública do município de Barbacena, Minas Gerais, Brasil. Métodos Trata-se de um estudo transversal realizado com escolares de 7 a 9 anos de ambos os sexos, matriculados na rede pública estadual de ensino. O consumo alimentar foi avaliado utilizando o Questionário Alimentar do Dia Anterior e o nível de atividade física pelo Questionário de Atividade Física do Dia Anterior. Os alimentos listados foram classificados segundo a extensão e propósito do processamento industrial, conforme proposto pela classificação NOVA. Na análise estatística foram utilizados os testes χ2 de Pearson, Exato de Fisher, χ2 com correção de Yates e regressão de Poisson, estimando-se a razão de prevalência bruta e ajustada, com intervalos de confiança de 95%. Resultados A prevalência de consumo de alimentos ultraprocessados foi de 69,6%. Após análises ajustadas, o consumo de alimentos ultraprocessados foi associado à omissão do café da manhã, lanche da tarde e ceia, baixo nível de atividade física e ao consumo de alimentos de risco. Por outro lado, o consumo de alimentos in natura ou minimamente processados foi associado à maior idade, consumo de almoço, lanche da tarde, jantar e alimentos protetivos. Conclusões Verificamos uma alta prevalência no consumo de alimentos ultraprocessados, associada a hábitos alimentares não saudáveis, em crianças escolares. Isso destaca a necessidade de ações de educação alimentar e nutricional, favorecendo o consumo alimentar saudável na infância.
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INTRODUCTION AND OBJECTIVES: Paravalvular leak (PVL) is a possible complication after prosthetic valve implantation. PVL can cause significant symptoms of congestive heart failure and/or hemolysis. Medical therapy is palliative and reoperation has a high mortality rate. Percutaneous transcatheter closure is a promising alternative for symptomatic patients at high surgical risk. We aim to review the efficacy and safety of percutaneous PVL closure in a consecutive series of patients referred to our center. METHODS: We performed a retrospective analysis of clinical and technical procedural data of patients referred to our center for percutaneous PVL closure between January 2009 and November 2015. RESULTS: Twenty procedures were performed in 18 patients under general anesthesia and under transesophageal echocardiographic and radiographic guidance. Fourteen mitral PVLs were successfully treated in 13 patients and one aortic PVL in one patient. Most (eight) of the PVLs closed were in mitral bioprostheses. Two patients underwent a second intervention, which was technically successful in one. Technical success was achieved in 15 (75%) of the procedures. At discharge, median NYHA functional class decreased by one and hemolytic anemia decreased from seven cases (38.9%) to two (11.1%). Two patients had minor bleeding at the femoral vascular access site. Survival rates at six, 12 and 24 months were 77.8%, 77.8% and 61.1%, respectively. CONCLUSIONS: In our experience, percutaneous PVL closure was overall effective and safe. The procedure is complex and a second intervention may be necessary. Percutaneous PVL closure may be a feasible alternative for selected symptomatic patients at high surgical risk refractory to medical therapy.
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Implante de Prótese de Valva Cardíaca/efeitos adversos , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgia , Idoso , Idoso de 80 Anos ou mais , Procedimentos Cirúrgicos Cardíacos/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
INTRODUCTION AND OBJECTIVES: The rate of implanted cardiac electronic devices is increasing as is the need to manage long-term complications. Lead removal is becoming an effective approach to treat such complications. We present our experience in lead removal using different approaches, analyzing the predictors of the use of mechanical extractors/surgical removal. METHODS: Retrospective analysis of lead extractions in a series of 76 consecutive patients (mean age 70.4 ± 13.8 years, 73.7% men) between January 2009 and November 2015. RESULTS: One hundred thirty-five leads from permanent pacemakers (single chamber 19.7%; dual-chamber 61.8%), implantable cardioverter defibrillators (5.3%), and cardiac resynchronization devices (CRT-P 2.6%; CRT-D 7.9%) were removed, 72.5 ± 73.2 months after implantation. A total of 45.9% were ventricular leads, 40.0% atrial leads, 8.9% defibrillator leads, and 5.2% leads in the coronary sinus; 64.4% had passive fixation. The most common indications for removal were pocket infection (77.8%), infective endocarditis (9.6%), and lead dislodgement (3.7%). A total of 76.3% of the leads were explanted, 20.0% were extracted, and 3.7% were surgically removed. Extraction of the entire lead was achieved in 96.3% of the procedures. After logistic regression (age adjusted), time since implantation was the sole predictor of the need of mechanical extractors/surgical removal. All patients were discharged without major complications. There were no deaths at 30 days. CONCLUSION: Our experience in lead removal was effective and safe. Performing these procedures by experienced electrophysiologists with an adequate cardiothoracic surgery team on standby to cope with any complications is required. Referral of high-risk patients to a high-volume center is recommended to optimize clinical success and minimize procedural complications.
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ABSTRACT Objective: To evaluate the sociodemographic and lifestyle factors associated with abdominal obesity in children from public schools in Barbacena, state of Minas Gerais, Brazil. Methods: This is a cross-sectional study conducted on 326 students aged 7 to 9 years from public schools in the urban area of the city. Anthropometric data included body weight, height, body mass index according to age, waist circumference, and waist-to-height ratio. Food consumption was evaluated using the Previous Day Food Questionnaire. Abdominal obesity was assessed based on waist circumference and waist-to-height ratio. The bivariate and multivariate analyses were performed by logistic regression, estimating the crude and adjusted odds ratio (OR), with 95% confidence interval. Results: The prevalence of overweight was 30.7%; whereas the prevalence of abdominal obesity was 9.2 and 12.6% according to waist circumference and waist-to-height ratio, respectively. Boys (OR 2.76; 95%CI 1.22-6.25) and children from central schools (OR 2.73; 95%CI 1.08-6.80) presented an increased chance of abdominal obesity according to waist circumference. Abdominal obesity according to waist-to-height ratio was associated with the central location of the schools (OR 2.18; 95%CI 1.02-4.63) and the habit of skipping supper (OR 2.01; 95%CI 1.00-4.09). Conclusions: The findings showed that being a boy, studying in a central school, and skipping supper were the main risk factors associated with abdominal obesity.
RESUMO Objetivo: Avaliar os fatores sociodemográficos e de estilo de vida associados à obesidade abdominal em crianças de escolas públicas de Barbacena, Minas Gerais. Métodos: Trata-se de estudo transversal realizado com 326 escolares de sete a nove anos, matriculados em escolas da zona urbana da cidade. As variáveis antropométricas avaliadas foram peso, estatura, índice de massa corpórea por idade, circunferência da cintura e relação cintura-estatura. O consumo alimentar foi registrado pelo Questionário Alimentar do Dia Anterior. A obesidade abdominal foi avaliada com base na circunferência da cintura e relação cintura-estatura. As análises bivariada e multivariada foram realizadas por meio de regressão logística, estimando-se a Odds Ratio (OR) bruta e ajustada, com os intervalos de confiança de 95% (IC95%). Resultados: A prevalência de excesso de peso foi de 30,7%, enquanto a prevalência de obesidade abdominal foi de 9,2 e 12,6%, de acordo com circunferência da cintura e relação cintura-estatura, respectivamente. Crianças do sexo masculino (OR 2,76; IC95% 1,22-6,25) e de escolas centrais (OR 2,73; IC95% 1,08-6,80) tiveram maior chance de apresentar obesidade abdominal segundo a circunferência da cintura. A obesidade abdominal, de acordo com a relação cintura-estatura, associou-se à localização central das escolas (OR 2,18; IC95% 1,02-4,63) e à omissão da ceia (OR 2,01; IC95% 1,00-4,09). Conclusões: Os achados mostraram que ser do sexo masculino, estudar em escola central e omitir a ceia foram os principais fatores de risco associados à obesidade abdominal.
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Thoracic endovascular aortic repair (TEVAR) is increasingly used in the treatment of acute type B aortic dissection. Type Ia endoleaks are a common complication of the procedure, but its clinical significance and the best treatment strategy remain poorly defined. We present a case of a type Ia endoleak following TEVAR in the treatment of acute type B aortic dissection. Chimney technique approach was used in an attempt to seal the endoleak. Although technical success was suboptimal, the patient remained clinically stable and event free. Data regarding the natural course and management of type Ia endoleaks following TEVAR for aortic dissection are sparse. Future research is required to establish the clinical and technical determinants of the need to treat these endoleaks and the best treatment strategy.
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To investigate which HIV-1 genetic forms are circulating in Angola, we have determined the gag and/or env genotypes of 48 isolates from patients living in Cabinda and Luanda provinces. The following subtypes were identified: A1 (18 samples, 38%), C (7, 15%), H (5, 10%), J (3, 6%), G (2, 4%), A2 (2, 4%), F1 (1, 2%), and D (1, 2%). The env gene fragment was untypable in one sample. Discordant subtype classifications in the gag and env genes were found in eight (17%) samples. There were six different recombination patterns (gag/env): A1/H (3, 6%), A1/G (1, 2%), C/A2 (1, 2%), F1/B (1, 2%), G/B (1, 2%), and G/H (1, 2%). The A1/H recombinant may represent a new circulating recombinant form. The marked genetic heterogeneity of HIV-1 in Angola has important implications for vaccine development.
Assuntos
Genes env , Genes gag , Infecções por HIV/virologia , HIV-1/classificação , HIV-1/genética , Polimorfismo Genético , Angola , Genótipo , HIV-1/isolamento & purificação , Humanos , Dados de Sequência Molecular , Filogenia , RNA Viral/genética , RNA Viral/isolamento & purificação , Recombinação Genética , Análise de Sequência de DNA , Proteínas Virais/genéticaAssuntos
Anormalidades Múltiplas/diagnóstico por imagem , Angiografia por Tomografia Computadorizada , Comunicação Interatrial/diagnóstico por imagem , Flebografia , Veias Pulmonares/diagnóstico por imagem , Síndrome de Cimitarra/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Veias Pulmonares/anormalidadesRESUMO
Aortic intramural hematoma (IMH) is an acute aortic syndrome characterized by bleeding into the media of the aortic wall without intimal disruption or the classic flap formation. Its natural history is variable and still poorly understood, so strategies for therapeutic management are not fully established. In some cases there is partial or complete regression of the hematoma under medical treatment, but most progress to dissection, aneurysmal dilatation or aortic rupture. The authors present the case of a 44-year-old hypertensive male patient admitted with a diagnosis of IMH of the descending aorta. Despite initial symptom resolution and optimal medical therapy, the IMH evolved to a pseudoaneurysm, which was successfully treated by an endovascular approach.