Raltegravir versus efavirenz in antiretroviral-naive pregnant women living with HIV (NICHD P1081): an open-label, randomised, controlled, phase 4 trial.

BACKGROUND: Although antiretroviral regimens containing integrase inhibitors rapidly suppress HIV viral load in non-pregnant adults, few published data from randomised controlled trials have compared the safety and efficacy of any integrase inhibitor to efavirenz when initiated during pregnancy. We compared safety and efficacy of antiretroviral therapy with either raltegravir or efavirenz in late pregnancy. METHODS: An open-label, randomised controlled trial was done at 19 hospitals and clinics in Argentina, Brazil, South Africa, Tanzania, Thailand, and the USA. Antiretroviral-naive pregnant women (20-<37 weeks gestation) living with HIV were assigned to antiretroviral regimens containing either raltegravir (400 mg twice daily) or efavirenz (600 mg each night) plus lamivudine 150 mg and zidovudine 300 mg twice daily (or approved alternative backbone regimen), using a web-based, permuted-block randomisation stratified by gestational age and backbone regimen. The primary efficacy outcome was plasma HIV viral load below 200 copies per mL at (or near) delivery. The primary efficacy analysis included all women with a viral load measurement at (or near) delivery who had viral load of at least 200 copies per mL before treatment and no genotypic resistance to any study drugs; secondary analyses eliminated these exclusion criteria. The primary safety analyses included all women who received study drug, and their infants. This trial is registered with Clinicaltrials.gov, number NCT01618305. FINDINGS: From Sep 5, 2013, to Dec 11, 2018, 408 women were enrolled (206 raltegravir, 202 efavirenz) and 394 delivered on-study (200 raltegravir, 194 efavirenz); 307 were included in the primary efficacy analysis (153 raltegravir, 154 efavirenz). 144 (94%) women in the raltegravir group and 129 (84%) in the efavirenz group met the primary efficacy outcome (absolute difference 10%, 95% CI 3-18; p=0·0015); the difference primarily occurred among women enrolling later in pregnancy (interaction p=0·040). Frequencies of severe or life-threatening adverse events were similar among mothers (30% in each group; 61 raltegravir, 59 efavirenz) and infants (25% in each group; 50 raltegravir, 48 efavirenz), with no treatment-related deaths. INTERPRETATION: Our findings support major guidelines. The integrase inhibitor dolutegravir is currently a preferred regimen for the prevention of perinatal HIV transmission with raltegravir recommended as a preferred or alternative integrase inhibitor for pregnant women living with HIV. FUNDING: Eunice Kennedy Shriver National Institute of Child Health and Human Development and National Institute of Allergy and Infectious Diseases.

Electrocardiographic and vectorcardiographic findings of patients undergoing reductive ventriculectomy (Batista operation).

BACKGROUND: The Batista operation, or partial ventriculectomy, has been designed by the Brazilian surgeon Dr. Randas Batista as an alternative method for treating patients with idiopathic dilated cardiomyopathy. HYPOTHESIS: This study aimed to analyze electro- and vectorcardiographic data obtained from patients who underwent such surgery, and to evaluate its electrical repercussions on the heart. METHODS: Pre- and postoperative electrocardiography (ECG) and vectorcardiography (VCG) were performed 45 days apart in 15 patients undergoing reductive ventriculectomy. RESULTS: All ECGs showed sinus rhythm, with unchanged QRS duration. Left atrial enlargement (86.6%) and left ventricular hypertrophy (100%) were the most common findings. Bundle-branch blocks (BBBs) were often demonstrated on preoperative studies, predominantly (46.7%) left BBBs. Left anterior fascicular blocks were seen in four patients (26.6%), one associated with right BBB. Electrocardiographic changes suggestive of myocardial infarction (MI) were seen in four patients preoperatively; postoperatively, all had extended to or within the lateral wall. Five additional patients developed lateral MIs postoperatively, for a total of 9 patients (60%) with postoperative signs of infarction (p < 0.05). Electro- and vectorcardiography also showed significant postoperative lowering of QRS voltages (mean 40.74%) in all patients and a consequent difficulty to diagnose left ventricular hypertrophy, although the morphologic features did not change. CONCLUSIONS: These important ECG and VCG alterations are reflections of both the surgical technique and its clinical consequences.

Variation of the Anthropometric Index for pectus excavatum relative to age, race, and sex.

OBJECTIVES: To determine possible variations in the Anthropometric Index for pectus excavatum relative to age, race, and sex in individuals free of thoracic wall deformities. METHODS: Between 2002 and 2012, 166 individuals with morphologically normal thoracic walls consented to have their chests and the perimeter of the lower third of the thorax measured according to the Anthropometric Index for pectus excavatum. The participant characteristics are presented (114 men and 52 women; 118 Caucasians and 48 people of African descent). RESULTS: Measurements of the Anthropometric Index for pectus excavatum were statistically significantly different between men and women (11-40 years old); however, no significant difference was found between Caucasians and people of African descent. For men, the index measurements were not significantly different across all of the age groups. For women, the index measurements were significantly lower for individuals aged 3 to 10 years old than for individuals aged 11 to 20 years old and 21 to 40 years old; however, no such difference was observed between women aged 11 to 20 years old and those aged 21 to 40 years old. CONCLUSION: In the sample, significant differences were observed between women aged 11 to 40 years old and the other age groups; however, there was no difference between Caucasian and people of African descent.

[Conflict of interest policies and disclosure requirements among European Society of Cardiology national cardiovascular journals]. / Políticas de conflictos de intereses y requisitos para su declaración en las revistas cardiovasculares nacionales de la Sociedad Europea de Cardiología.

Disclosure of potential conflicts of interest is used by biomedical journals to guarantee credibility and transparency of the scientific process. Conflict of interest disclosure, however, is not systematically nor consistently dealt with by journals. Recent joint editorial efforts paved the way towards the implementation of uniform vehicles for conflicts of interest disclosure. This paper provides a comprehensive editorial perspective on classical conflict of interest-related issues. New insights into current conflicts of interest policies and practices among European Society of Cardiology national cardiovascular journals, as derived from a cross-sectional survey using a standardized questionnaire, are discussed.

Effects of azathioprine on mucociliary clearance after bronchial section and anastomosis in a rat experimental model.

OBJECTIVE: To evaluate the effects of azathioprine on the mucociliary system in a model of bronchial section and anastomosis in rats. METHODS: Thirty-six male Wistar-Furth rats were submitted to left bronchial section and anastomosis and divided into two groups to receive either saline solution or azathioprine. After 7, 15 and 30 days of treatment, six animals from each group were killed, after which in situ mucociliary transport velocity, in vitro mucus transportability, and contact angle of mucus in the right (intact) and left (sectioned) bronchi were measured. RESULTS: In situ mucociliary transport velocity was significantly lower in the sectioned bronchi than in the intact bronchi (p < 0.001). In situ mucociliary transport velocity was lower in the intact bronchi of the animals treated with azathioprine for 7 days (p < 0.05), and those bronchi presented full recovery after 30 days of treatment. The contact angle was higher in the mucus samples collected from the sectioned bronchi of the animals treated with saline solution for 30 days (p < 0.001), which is in accordance with the decreased in vitro mucus transportability observed in the same animals (p < 0.001). CONCLUSIONS: We conclude that, in the sectioned bronchi of rats, treatment with azathioprine causes only transitory impairment of mucociliary transport, whereas administration of saline solution impairs mucociliary transport for up to 30 days. In addition, azathioprine protects against alterations in mucus surface properties.

Variation of the Anthropometric Index for pectus excavatum relative to age, race, and sex

OBJECTIVES: To determine possible variations in the Anthropometric Index for pectus excavatum relative to age, race, and sex in individuals free of thoracic wall deformities. METHODS: Between 2002 and 2012, 166 individuals with morphologically normal thoracic walls consented to have their chests and the perimeter of the lower third of the thorax measured according to the Anthropometric Index for pectus excavatum. The participant characteristics are presented (114 men and 52 women; 118 Caucasians and 48 people of African descent). RESULTS: Measurements of the Anthropometric Index for pectus excavatum were statistically significantly different between men and women (11-40 years old); however, no significant difference was found between Caucasians and people of African descent. For men, the index measurements were not significantly different across all of the age groups. For women, the index measurements were significantly lower for individuals aged 3 to 10 years old than for individuals aged 11 to 20 years old and 21 to 40 years old; however, no such difference was observed between women aged 11 to 20 years old and those aged 21 to 40 years old. CONCLUSION: In the sample, significant differences were observed between women aged 11 to 40 years old and the other age groups; however, there was no difference between Caucasian and people of African descent. .

Body surface potential mapping investigating the ventricular activation patterns in the cardiac resynchronization of patients with left bundle-branch block and heart failure.

Body surface potential mapping assessed mean cardiac electrical activation times displayed by isochronal maps in the right ventricle (RV; right ventricle mean activation time [mRV]), anterior septal area (anterior septal area mean activation time [mAS]), and left ventricle (left ventricle mean activation time [mLV]) of 28 patients (mean, 61.07 years; congestive heart failure class III-IV; ejection fraction, < or =40%; left bundle-branch block [LBBB] QRS, 180.17 milliseconds), before and after biventricular pacemaker implantation, comparing them, using reference values from a control group of healthy individuals with normal hearts (GNL), in (1) baseline native LBBB, where mRV and mAS values were similar (40.99 vs 43.62 milliseconds), with mLV delayed (80.99 milliseconds, P < .01) and dyssynchronous with RV/anterior septal area; (2) single-site RV pacing, where mRV was greater than in GNL (86.82 milliseconds, P < .001), with greater mAS/mLV difference (63.41 vs 102.7 milliseconds; P < .001); and (3) biventricular pacing (BIV-PM), where mLV and mRV were similar (71.99 vs 71.58 milliseconds), mRV was greater than in GNL and native LBBB (71.58 vs 35.1 and 40.99 milliseconds; P < .001), and mAS approached values in GNL and native LBBB (51.28 vs 50.14 and 43.62 milliseconds). Body surface potential mapping showed that similar RV/left ventricle activation times during biventricular pacing, nearing mAS, indicate synchronized ventricular activation pattern in patients with congestive heart failure/LBBB.

QT interval dispersion analysis in patients undergoing left partial ventriculectomy (Batista operation).

BACKGROUND: QT interval dispersion (QTd) has been valued as a marker of increased vulnerability for cardiac arrhythmias. QTd was analyzed in patients undergoing the left partial ventriculectomy (LPV) or Batista operation, a palliative surgery for patients in the line for heart transplantation, which is associated with complex arrhythmia and death from sustained ventricular tachyarrhythmia (SVT). METHODS: Pre- and postoperative R-R, QT, QTc, JT (QT - QRS), and aT (apex to end of T wave) intervals were obtained by 87-lead body surface mapping from 24 patients (18 male), mean age 46.4 +/- 9.15 years. Dispersions of QT, QTc, JT, and aT intervals were calculated, and the total number of arrhythmic events were assessed, aiming to verify a possible risk predictor for the occurrence of SVTs. Subgroups of patients who survived and who died after LPV were also compared, aiming to obtain a QTd cutoff value that could be used prognostically. RESULTS: No difference between pre- and postoperative mean values were found, but a very significant difference was seen when comparing QTd and QTcD values for surviving and dead patients: QTd, cutoff value was 95 ms, while QTcD value was 114 ms. CONCLUSION: There were no significant differences between pre- and postoperative variables or the number of arrhythmic events, but there were significant differences between both pre- and postoperative QTd and QTcD data from surviving and dead patients; this enabled the determination of cutoff values that we believe may be useful for the prognosis of the LPV outcome.

Efeitos da azatioprina sobre a depuração mucociliar após secção e anastomose brônquica em um modelo experimental em ratos / Effects of azathioprine on mucociliary clearance after bronchial section and anastomosis in a rat experimental model

OBJETIVO: Avaliar os efeitos da azatioprina sobre o sistema mucociliar em um modelo de secção e anastomose brônquica em ratos. MÉTODOS: Trinta e seis ratos machos da raça Wistar-Furth foram submetidos à secção e anastomose brônquica esquerda e separados aleatoriamente em dois grupos para receberem solução salina ou azatioprina. Após 7, 15 e 30 dias de terapia, seis animais de cada grupo foram sacrificados, e foram realizadas as medidas da velocidade de transporte mucociliar in situ, da transportabilidade do muco in vitro e do ângulo de contato do muco nos brônquios direito (intacto) e esquerdo (seccionado). RESULTADOS: A velocidade de transporte mucociliar in situ foi significativamente menor nos brônquios seccionados do que nos brônquios intactos (p < 0,001). Houve redução da velocidade de transporte mucociliar in situ nos brônquios intactos dos animais tratados com azatioprina por 7 dias (p < 0,05), havendo completa recuperação após 30 dias de terapia. O ângulo de contato do muco foi maior nos brônquios seccionados dos animais tratados com solução salina por 30 dias (p < 0,001), estando de acordo com a redução da transportabilidade do muco in vitro observada nos mesmos animais (p < 0,001). CONCLUSÕES: Concluímos que, nos brônquios seccionados de ratos, a terapia com azatioprina causa um prejuízo apenas transitório do transporte mucociliar, enquanto a administração de solução salina prejudica o transporte mucociliar por até 30 dias. Além disso, a azatioprina contribui para prevenir alterações nas propriedades da superfície do muco.

OBJECTIVE: To evaluate the effects of azathioprine on the mucociliary system in a model of bronchial section and anastomosis in rats. METHODS: Thirty-six male Wistar-Furth rats were submitted to left bronchial section and anastomosis and divided into two groups to receive either saline solution or azathioprine. After 7, 15 and 30 days of treatment, six animals from each group were killed, after which in situ mucociliary transport velocity, in vitro mucus transportability, and contact angle of mucus in the right (intact) and left (sectioned) bronchi were measured. RESULTS: In situ mucociliary transport velocity was significantly lower in the sectioned bronchi than in the intact bronchi (p < 0.001). In situ mucociliary transport velocity was lower in the intact bronchi of the animals treated with azathioprine for 7 days (p < 0.05), and those bronchi presented full recovery after 30 days of treatment. The contact angle was higher in the mucus samples collected from the sectioned bronchi of the animals treated with saline solution for 30 days (p < 0.001), which is in accordance with the decreased in vitro mucus transportability observed in the same animals (p < 0.001). CONCLUSIONS: We conclude that, in the sectioned bronchi of rats, treatment with azathioprine causes only transitory impairment of mucociliary transport, whereas administration of saline solution impairs mucociliary transport for up to 30 days. In addition, azathioprine protects against alterations in mucus surface properties.

Uso do baläo intra-aórtico no choque cardiogênico no pós-operatório de cirurgia cardíaca: análise prospectiva durante 22 meses / Intra-aortic balloon pump for postcarditomy heart failure: prospective analysis over 22 months

Intra-aortic balloon pump is a cardiac assist device developed to help in recovery from postcardiotomy heart failure. All patients submitted to intra-aortic balloon pump were followed prospectively at the Instituto do Coração do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo-InCor over a period of 22 months. Although we did not find statistically significant evidence of correlation between mortality and patient data (Surgery done, emergency or not, redo or not, age, gender, medical problem, functional class, cardiac function, clamp, bypass, and support time and complications) the evaluation showed our patient universe in the InCor Institute.

Arritmias após transplante cardíaco ortotópico / Arrhythmias After Orthotopic Heart Transplantation

PURPOSE--To correlate the incidence of arrhythmias to the degree of allograft rejection on endomyocardial biopsy. METHODS--Seventeen patients who underwent orthotopic heart transplantation were submitted to ambulatory Holter monitoring 24h prior to endomyocardial biopsy. The biopsy results were compared to Holter monitoring results. RESULTS--The mean study period was 252 +/- 166 days (15 to 515). We found a high incidence of ventricular premature beats (> 70 per cent), except in patients with severe rejection (25 per cent), but there was no statistically significant difference between the groups with no rejection, mild and moderate rejection. Atrial premature beats were more common in patients with mild and moderate rejection (53 per cent and 70 per cent, respectively) when compared to patients with no rejection (33 per cent) and patients with severe rejection (9 per cent), (p < 0.05). Sinus bradycardia was present in 50 per cent of patients with severe rejection, but only in 9 per cent of moderate, 3 per cent of mild and 5 per cent of the patients with no rejection (p < 0.05). CONCLUSION--Supraventricular tachycardia and atrial premature beats are related to moderate rejection. Ventricular premature beats are not related to degree of rejection. Sinus bradycardia occurring in the first year after transplantation should suggest severe cardiac allograft rejection

Avaliação hemodinâmica durante exercício isotônico em pacientes submetidos a transplante cardíaco ortotópico / Hemodynamic Evalution During Isotonic Exercise of Patients Submitted to Orthotopic Heart Transpantation

PURPOSE--To evaluate the hemodynamic response of patients submitted to orthotopic heart transplantation during progressive isotonic exercise. METHODS--Eight patients who underwent orthotopic heart transplantation have been evaluated through invasive hemodynamic study during isotonic exercise. The mean right atrial pressure (RAP), pulmonary artery pressure (PAP), pulmonary artery wedge pressure (PAWP), arterial blood pressure (ABP), systemic vascular resistance (SVR), pulmonary vascular resistance (PVR), heart rate (HR) and cardiac output (CO) have been determined in three distinct situations: at rest in the supine position (R), at rest with the legs up (RU) and during progressive isotonic exercise (E). The hemodynamic results at rest have been compared to the ones before transplantation. Phase RU and E results have been compared with each other. RESULTS--Comparing to the phase before transplantation at the R phase we found normalization of mean PAP (34.9 +/- 14.0 to 17.0 +/- 3.5 mmHg), RAP (7.3 +/- 4.3 to 2.9 +/- 1.9 mmHg) and CO (2.9 +/- 0.98 to 5.7 +/- 0.99 l/min), otherwise there was an increase in HR (89 +/- 15 to 94 +/- 13 bpm) mean ABP (84 +/- 25 to 115 +/- 12 mmH) and SVR (30 +/- 15 to 22 +/- 7 units Wood), (p < 0.05). Comparing phase E to phase RU, there was a significant increase in RAP (3.1 +/- 1.8 to 9.4 +/- 3.9 mmHg), mean PAP (21.0 +/- 2.8 to 37.0 +/- 10.0 mmHg), PAWP (8.1 +/- 2.1 to 15.0 +/- 5.8 mmHg), CO (5.8 +/- 0.8 to 9.9 +/- 2.4 l/min), HR (93 +/- 8 to 116 +/- 18 bpm) and a decrease in SVR (22.0 +/- 3.0 to 13.3 +/- 3.8 units Wood), (p < 0.05), otherwise there was no statistically significant modifications in PVR (2.2 +/- 0.7 to 2.3 +/- 1.2 units Wood) and mean ABP (129 +/- 12 to 129 +/- 15 mmHg), (p = NS). CONCLUSION--Patients submitted to heart transplantation may improve cardiac output mainly from increasing in stroke volume, associated with an increase in RAP and PAP. Nevertheless, the improvement increase in CO is compatible to exercise capacity after heart transplantation

Influência da lidocaína na proteção miocárdica com solução cardioplégica sangüínea / It influences of the lidocaine in efficacy with cardioplegic solution myocardial

OBJETIVO: Avaliar a eficácia da proteção miocárdica obtida com o acréscimo da lidocaína à solução sangüínea hipercalêmica normotérmica. MÉTODO: Foram estudados 26 cães, divididos em dois grupos de dez animais e um grupo de seis, de forma aleatória, conforme a solução cardioplégica de indução que receberam. O grupo I recebeu a solução composta por lidocaína 5mg/kg, cloreto de potássio 41,6mEq/l em 180ml de sangue normotérmico. O grupo II recebeu a solução anterior sem lidocaína e o grupo III recebeu somente os 180ml de sangue. A solução de manutenção foi a mesma para os 3 grupos composta por 120ml de sangue normotérmico, reinfundidos a cada 20min. Os animais foram submetidos à circulação extracorpórea, a duas horas de isquemia miocárdica e três horas de reperfusão. Foram avaliados mortalidade operatória, dosagens seriadas de troponina I, creatina quinase e lactado, débito cardíaco, fração de ejeção e fração de área das mitocôndrias. A análise estatística foi através dos testes exato de Fisher e a análise de variância de duplo fator complementada com o teste de Bonferroni. RESULTADO: O grupo I apresentou menor mortalidade (p=0,08), menor liberação da creatina quinase (p<0,05) e menor comprometimento mitocondrial (p=0,036). Não houve diferença entre os grupos quanto à liberação de troponina I, lactato e avaliação hemodinâmica. CONCLUSÃO: Pode-se concluir que a lidocaína conferiu efeito protetor adicional ao miocárdio isquêmico e que os animais dos grupos I e II apresentaram alterações significativas, sugestivas de dano celular, com repercussões funcionais, para todos os parâmetros avaliados no decorrer do tempo

Biopsia endomiocárdica do ventrículo direito: 9 anos (1978 a 1987) / Endomyocardial biopsy of the right ventricle: 9 years (1978 to 1987)

No periodo de 1978 a março de 1987 foram realizadas 695 biopsias do ventriculo direito. As indicaçöes mais freqüentes para a biopsia foram: transplante cardíaco, miocardiopatia dilatada, doença de Chagas e fibrose endomiocárdica. A experiência adquirida com o tempo diminuiu os insucessos de 12,9% no período de 1978 a 1983 para 1,3% de 1984 a 1986. O mesmo aconteceu com as complicaçöes, que diminuíram de 1,2% para 0,5%. Em conclusäo, a biopsia se confirmou como método de grande utilidade no diagnóstico e controle da rejeiçäo cardíaca e no diagnóstico e evoluçäo das miocardites, indicaçöes hoje preferenciais na nossa Instituiçäo para a biopsia. Em 9 anos, como método propedêutico de rotina, mostrou-se método seguro e sem mortalidade