Efficacy, safety, tolerability, and pharmacokinetics of long-acting injectable cabotegravir for HIV pre-exposure prophylaxis in transgender women: a secondary analysis of the HPTN 083 trial.

BACKGROUND: The HIV Prevention Trials Network (HPTN) 083 trial showed that long-acting injectable cabotegravir was more effective than tenofovir disoproxil fumarate plus emtricitabine in preventing HIV in cisgender men and transgender women who have sex with men. We aimed to characterise the cohort of transgender women included in HPTN 083. METHODS: HPTN 083 is an ongoing, phase 2b/3, randomised, multicentre, double-blind, double-dummy clinical trial done at 43 sites in seven countries (Argentina, Brazil, Peru, the USA, South Africa, Thailand, and Viet Nam). HIV-negative participants were randomly assigned (1:1) to receive injectable cabotegravir or tenofovir disoproxil fumarate plus emtricitabine. The study design and primary outcomes of the blinded phase of HPTN 083 have already been reported. An enrolment minimum of 10% transgender women was set for the trial. Here we characterise the cohort of transgender women enrolled from Dec 6, 2016, to May 14, 2020, when the study was unblinded. We report sociodemographic characteristics, use of gender affirming hormone therapy, and behavioural assessments of the transgender women participants. Laboratory testing and safety evaluations are also reported. The trial is registered at ClinicalTrials.gov, NCT02720094. FINDINGS: HPTN 083 enrolled 570 transgender women (304 tenofovir disoproxil fumarate plus emtricitabine; 266 injectable cabotegravir). Transgender women were primarily from Asia (225 [39%]) and Latin America (205 [36%]); 330 (58%) reported using gender affirming hormone therapy. Intimate partner violence was common (270 [47%] reported emotional abuse and 172 [30%] reported physical abuse) and 323 (57%) reported a history of childhood sexual abuse. 159 (28%) transgender women disagreed that they were at risk for HIV, and 142 (25%) screened positive for depressive symptoms. During study follow-up, incidence of syphilis was 16·25% (95% CI 13·28-19·69), rectal gonorrhoea was 11·66% (9·14-14·66), and chlamydia was 20·61% (17·20-24·49). Frequency of adverse events was similar between the treatment groups. Nine seroconversions occurred among transgender women during the blinded phase of the study (seven in the tenofovir disoproxil fumarate plus emtricitabine group and two in the injectable cabotegravir group); overall incidence was 1·19 per 100 person-years (95% CI 0·54-2·25): 1·80 per 100 person-years (0·73-3·72) in the tenofovir disoproxil fumarate plus emtricitabine group and 0·54 per 100 person-years (0·07-1·95) in the injectable cabotegravir group (hazard ratio 0·34 [95% CI 0·08-1·56]). Cabotegravir concentrations did not differ by gender affirming hormone therapy use. INTERPRETATION: HIV prevention strategies for transgender women cannot be addressed separately from social and structural vulnerabilities. Transgender women were well represented in HPTN 083 and should continue to be prioritised in HIV prevention studies. Our results suggest that injectable cabotegravir is a safe and effective pre-exposure prophylaxis option for transgender women. FUNDING: National Institute of Allergy and Infectious Diseases and ViiV Healthcare.

Acromegaly and Colorectal Neoplasm: An Update.

Acromegaly is a systemic disease caused by excessive inappropriate secretion of GH and IGF-I levels, resulting in many systemic complications, including cardiovascular, respiratory, metabolic diseases, and a possible increased risk of some neoplasias. Although many studies on acromegaly and cancer remain uncertain, most data indicate that colorectal cancer (CRC) incidence is increased in this population. The exact mechanism involved in the role of GH-IGF-I axis in CRC has not been fully explained, yet it is associated with local and circulating effects of GH and IGF-I on the colon, promoting angiogenesis, cell proliferation, risk of mutation, inhibition of tumor-suppressor genes and apoptosis, thus facilitating a tumor microenvironment. Nevertheless, population-based studies present controversial findings on CRC incidence and mortality. All worldwide guidelines and expert consensuses agree with the need for colonoscopic screening and surveillance in acromegaly, although there is no consensus regarding the best period to do this. This review aims to analyze the existing data on CRC and acromegaly, exploring its pathophysiology, epidemiological studies and their limitations, colonic polyp characteristics, overall cancer and CRC incidences and mortality, risk factors for colon cancer pathophysiology, and recommendation guideline aspects.

Nandrolone decanoate is prooxidant in the myocardium of exercised or sedentary rats / Decanoato de nandrolona é pro-oxidante no miocárdio de ratos treinados e sedentários / Decanoato de nandrolona es prooxidante en el miocardio de ratones entrenados y sedentarios

ABSTRACT Introduction: Nandrolone decanoate is a synthetic testosterone analogue considered one of the most widely used anabolic androgenic steroids (AAS) among adolescents and athletes. Chronic ingestion of AAS increases the incidence of cardiovascular abnormalities in athletes, but the mechanism that causes these changes remains unknown. Objectives: The purpose of this study is to verify the possible effects of the use of anabolic androgenic steroids (AAS) on the morphology and oxidative metabolism of the heart in exercised and sedentary rats. Methods: This is a comparative prospective level II study. Twenty-four Wistar rats were distributed in groups that performed voluntary (TG) and sedentary (SG) running exercises, and used AAS: the Anabolic Training Group (ATG), and the Anabolic Sedentary Group (ASG). During the three months of the running protocol, the animals received an intramuscular injection of 5 mg/kg b.p. of AAS. After the training period, the rats were euthanized and the hearts were removed for evaluation of lipid peroxidation and antioxidant capacity, and for morphometric analysis. Results: The anabolic groups, ASG (0.3072 ± 0.0531) and ATG (0.2732 ± 0.0413), presented higher lipid peroxidation when compared to the non-anabolic groups SG (0.1705 ± 0.0224) and TG (0.1785 ± 0.0340). Conclusion: There was no change in total antioxidant capacity or in the thickness of the interventricular septum and left ventricular wall. Thus, the use of anabolic androgenic steroids did not cause morphological changes in the myocardium. However it did alter the oxidative metabolism. It was also verified that aerobic exercise had no protective effect against lipid peroxidation in the myocardium caused by the use of AAS. Level of evidence II; Prospective comparative study.

RESUMO Introdução: O decanoato de nandrolona é um análogo sintético da testosterona, considerado um dos esteroides anabólicos androgênicos (EAA) mais utilizados entre adolescentes e atletas. Sua ingestão crônica aumenta a incidência de anormalidades cardiovasculares em atletas, porém o mecanismo que causa essas alterações ainda permanece desconhecido. Objetivos: O estudo teve como objetivo verificar os possíveis efeitos do uso de esteroides anabólicos androgênicos (EAA) na morfologia e no metabolismo oxidativo do coração de ratos treinados e sedentários. Métodos: Trata-se de um estudo prospectivo comparativo nível II. Vinte e quatro ratos Wistar foram distribuídos em grupos que realizaram exercícios de corrida voluntária (GT) e sedentários (GS) e faziam uso dos EAA, Grupo Treinado com Anabolizante (GTA) e Grupo Sedentário com Anabolizante (GSA). Durante os três meses do protocolo de corrida, os animais receberam injeção intramuscular de 5 mg/kg p.c. de EAA. Após o período de treinamento, houve a eutanásia e remoção do coração dos ratos para avaliação da peroxidação lipídica e capacidade antioxidante, além da análise morfométrica. Resultados: Verificaram-se que os grupos anabolizantes, GSA (0,3072 ± 0,0531) e GTA (0,2732 ± 0,0413), apresentaram maior peroxidação lipídica quando comparados aos grupos não anabolizantes GS (0,1705 ± 0,0224) e GT (0,1785 ± 0,0340). Conclusões: Não houve alteração na capacidade antioxidante total, assim como não houve alteração na espessura do septo interventricular e da parede ventricular esquerda. Portanto, o uso de esteroides anabólicos androgênicos não provocou alterações morfológicas no miocárdio, contudo alterou o metabolismo oxidativo. Verificou-se também que a prática de exercício aeróbico não teve efeito protetor contra a peroxidação lipídica no miocárdio provocada pelo uso dos EAA. Nível de evidência II; Estudo prospectivo comparativo.

RESUMEN Introducción: El decanoato de nandrolona es un análogo sintético de la testosterona considerado uno de los esteroides anabólicos androgénicos (EAA) más utilizados entre los adolescentes y atletas. Su ingestión crónica aumenta la incidencia de anomalías cardiovasculares en atletas, aunque el mecanismo que causa esas alteraciones sigue siendo desconocido. Objetivos: El estudio tuvo como objetivo verificar los posibles efectos del uso de esteroides anabólicos androgénicos (EAA) en la morfología y en el metabolismo oxidativo del corazón de ratones entrenados y sedentarios. Métodos: Se trata de un estudio prospectivo comparativo nivel II. Fueron distribuidos 24 ratones Wistar en grupos que realizaron ejercicios de carrera voluntaria (GE) y sedentarios (GS), y hacían uso de los EAA, Grupo Entrenado con Anabolizante (GEA) y Grupo Sedentario con Anabolizante (GSA). Durante los tres meses del protocolo de carrera, los animales recibieron inyección intramuscular de 5 mg/kg p.c. de EAA. Después del período de entrenamiento, hubo la eutanasia y remoción del corazón de los ratones, para evaluación de la peroxidación lipídica y capacidad antioxidante, además del análisis morfométrico. Resultados: Se verificó que los grupos anabolizantes, GSA (0,3072 ± 0,0531) y GEA (0,2732 ± 0,0413), presentaron mayor peroxidación lipídica cuando comparados a los grupos no anabolizantes GS (0,1705 ± 0,0224) y GE (0,1785 ± 0,0340). Conclusiones: No hubo alteración en la capacidad antioxidante total, así como no hubo alteración en el espesor del septo interventricular y de la pared ventricular izquierda. Por lo tanto, el uso de esteroides anabólicos androgénicos no provocó alteraciones morfológicas en el miocardio, aunque alteró el metabolismo oxidativo. Se verificó también que la práctica de ejercicio aeróbico no tuvo efecto protector contra la peroxidación lipídica en el miocardio provocada por el uso de EAA. Nivel de evidencia II; Estudio prospectivo comparativo.

Novel therapies for acromegaly.

Acromegaly is a systemic disease associated with increased morbidity and mortality. Most of these comorbidities can be prevented or delayed with adequate disease treatment. Although three modalities of treatment (surgery, medical treatment, and radiotherapy) are available and new drugs were approved in the last decades, there are still some patients that maintain disease activity despite treatment. Therefore, there is a need for novel therapies for acromegaly and for that purpose new formulations of currently used drugs and also new drugs are currently under study. In this review, we summarize the novel therapies for acromegaly.

Effects of nandrolone decanoate on spermatogenesis in Wistar rats with and without physical training / Efectos del decanoato de nandrolona sobre la espermatogénesis en ratas Wistar con y sin entrenamiento físico

Androgenic anabolic steroids (AAS) are artificial testosterone analogues, used as medicine in chronic diseases, because they increase protein synthesis generating muscle hypertrophy. Its effect has caught the attention of athletes and gym users, thus their consumption has become epidemic, due to easy marketing, the immediate results and the false impression that it doesn't carry health risks. Such risks may globally harm the body. This study aims to investigate the influence on spermatogenesis of using nandrolone decanoate with or without physical training. Twenty-four rats, divided into four groups were used: sedentary group (SG), sedentary on steroids group (SSG), trained group (TG) and trained on steroids group (TSG). The animals were trained on voluntary exercise wheel twice a week during 12 weeks, and were subsequently euthanized by decapitation. Groups TSG and SSG received intramuscular injections of 5 mg / kg of the AAS. It was found that there was a greater cellularity in TSG, suggesting interference between androgen therapy and physical training on the mount of cells in the seminiferous epithelium. Comparing the TSG group with the SG, it is noticed that the physical training associated with the use of steroid tends to affect cell division without compromise, however, the number of spermatogonia, did not significantly vary compared to the control group. Finally, it seems that there was no significant statistical difference among the groups in terms of spermatogenesis yield, so that can not be said that the use of nandrolone decanoate, with or without the physical training, interfere with fertility.

Los esteroides anabólicos androgénicos (EAA) son análogos de testosterona artificiales, utilizados como medicina en las enfermedades crónicas, ya que aumentan la síntesis de proteínas generando hipertrofia muscular. Su efecto ha llamado la atención de atletas y usuarios de gimnasios, por lo que su consumo se ha convertido en epidemia, debido a la comercialización fácil, los resultados inmediatos y la falsa impresión de que no conllevan riesgos para la salud. Este estudio tiene como objetivo investigar la influencia de utilizar decanoato de nandrolona con o sin entrenamiento físico sobre la espermatogénesis. Se utilizaron 24 ratas, divididas en cuatro grupos: entrenado (GE), entrenado en esteroides (GEE), sedentario en esteroides (GSE) y sedentario (GS). Los grupos GEE y GSE recibieron inyecciones intramusculares de 5 mg/kg de la EAA. Los animales fueron entrenados con ejercicio voluntario en la rueda de correr dos veces por semana durante 12 semanas. Luego, los animales fueron sacrificados por decapitación. Se encontró que hubo una mayor celularidad en GEE, lo que sugiere la interferencia entre la terapia con andrógenos y entrenamiento físico en la cantidad de células en el epitelio seminífero. Comparando el grupo GEE con el GS, se observa que el entrenamiento físico asociado con el uso de esteroides tiende a afectar a la división celular sin comprometerla, sin embargo, el número de espermatogonias, no varió significativamente en comparación con el grupo control. Finalmente, no hubo diferencia significativa entre los grupos en términos de rendimiento de la espermatogénesis, por lo que no se puede decir que el uso del decanoato de nandrolona, con o sin el entrenamiento físico, interfiere con la fertilidad.

Infecção congênita em pacientes matriculados em Programa de referência materno infantil / Congenital infection in patients enrolled in mother child preference program

Objetivo: Caracterizar o perfil epidemiológico dos recém-nascidos de risco com infecção congênita atendidos naUnidade de Referência Materno Infantil e Adolescente/URE-MIA, em Belém/PA. Método: estudo retrospectivo noqual foram analisados os prontuários de todos os pacientes matriculados no Programa de RN de Risco da URE-MIAcom diagnóstico de infecção congênita, entre 2008 e 2013, a partir de protocolo elaborado pelos pesquisadores,totalizando casuística de 186 (cento e oitenta e seis) indivíduos. Resultados: Observou-se a sífilis congênita comoinfecção mais frequente, totalizando 147 casos, dentre os 186 pacientes; seguida por toxoplasmose e citomegalovirose,respectivamente. A maioria (66,6%) das mães realizou pré-natal completo, sugerindo baixa qualidade do serviçoofertado às gestantes, principalmente no que diz respeito à triagem das infecções congênitas. Conclusão: Constatouseque o alarmante recrudescimento da sífilis congênita na população estudada, bem como as demais infecções quefiguraram nesta pesquisa, podem ser relacionadas a um pré-natal ineficiente, suscitando, portanto, maior investimentoe olhar crítico dos agentes de saúde para a necessidade de um sistema pré-natal efetivo na prevenção de doençaspassíveis de tratamento, durante a gestação.

Objective: characterize the epidemiological profile of newborns with congenital infection risk treated at the MaternalChild and Adolescent Reference / URE-MIA in Belém / PA. Method: retrospective and cross-sectional study inwhich the medical records of all patients enrolled in the URE-MIA Program NB Risk with congenital infectionbetween 2008 and 2013, from protocol developed by the researchers analyzed a total sample of 186 (one hundredand eighty-six) individuals. Results: Syphilis was observed as the most frequent congenital infection, totalizing 147cases among 186 patients; followed by congenital toxoplasmosis and cytomegalovirus, respectively. The majority of(66.6%) mothers held complete prenatal, suggesting poor quality of the service offered to pregnant women, especiallywith regard to the screening of congenital infections. Conclusion: This study concludes that alarming resurgenceof congenital syphilis in this population, as well as other infections that figured in this research, may be related toan inefficient prenatal, thus posing greater investment and critical eye from health workers to the necessity of aneffective system in prenatal prevention of diseases susceptible to treatment during pregnancy.

Perfil epidemiológico de pacientes vítimas de escalpelamento tratados na Fundação Santa Casa de Misericórdia do Pará / Epidemiological profile of scalping victim-patients treated at the Fundação Santa Casa de Misericórdia do Pará

INTRODUÇÃO: Escalpelamento é trauma causado por avulsão parcial ou total do couro cabeludo, decorrente, principalmente, de contato acidental dos cabelos longos com motor de eixo rotativo. A alta rotação desses motores gera uma força que suga os cabelos da vítima, tracionando e arrancando o couro cabeludo de forma abrupta. MÉTODO: Foi realizado um estudo observacional transversal, retrospectivo, descritivo, incluindo 62 pacientes vítimas de escalpelamento tratados na Fundação Santa Casa de Misericórdia do Pará. RESULTADOS: Os pacientes mais acometidos foram crianças de 7 anos a 16 anos (56,4%), do gênero feminino (93,5%), sendo 59,7% estudantes e que, predominantemente, praticavam a religião católica (43,5%). CONCLUSÕES: Campanhas profiláticas sobre os riscos de se viajar e manter uma embarcação sem proteção no eixo do motor são fundamentais, uma vez que a tragédia do escalpelamento é causada principalmente pelos cabelos que se enrolam no eixo do motor.

BACKGROUND: Scalping is a trauma caused by partial or total avulsion of the scalp. It is primarily due to accidental contact of long hair with the rotary shaft of a motor. Rotary shafts suck in the victim's hair, causing traction and abruptly pulling the scalp off. METHODS: A longitudinal, observational, retrospective, and descriptive study of 62 scalping victim-patients treated at Fundação Santa Casa de Misericórdia do Pará was conducted. RESULTS: The most commonly affected patients were children between 7 and 16 years of age (56.4%) and women (93.5%); 59.7% were students and 43.5% were Catholics. CONCLUSIONS: Prophylactic campaigns about the risks of traveling in and maintaining a vessel without motor shaft protection are essential because scalping is primarily caused by hair twisting around the motor shaft.

Intake, digestibility, performance, and carcass traits of beef cattle of different gender.

The performance, intake, feed efficiency, and carcass traits of beef cattle from different gender profile were assessed. Fifteen animals (five steers, five spayed heifers, and five intact heifers) with ±250 kg of initial body weight were randomly assigned in individual pens and fed the same diet for 106 days. At the end of the trial, all the animals were slaughtered and the pH, temperature, and weight of the carcass were recorded. The right side of each carcass was then separated into chuck, shoulder, flank sirloin, and round for evaluation of commercial cuts yield. The left carcass sides were ribbed between the 12th and 13th ribs where the rib eye area and fat thickness measurements were taken. The 9th-11th rib section was removed from the left half carcass and then dissected into muscle, fat, and bones in order to estimate carcass composition. Gender had no effect (P > 0.05) on performance, intake, digestibility of dry matter and all the nutrients evaluated, feed efficiency, and carcass characteristics. It can be concluded that steers and heifers (spayed or not) have the same potential to produce beef. From a productive and welfare standpoint, there is no reason to spay heifers.