Diagnóstico citogenético e malformações congênitas: uma analise em Roraima

Introduction: The lack of specialized care for congenital malformations and a genetic diagnosis service makes it difficult to register and monitor cases. Objective: This work aimed to investigate the main genetic anomalies that affect individuals with congenital malformations in the state of Roraima, based on the consultation of medical records and application of questionnaires. Methods: Fifty nine questionnaires were applied to mothers or pregnant women who were receiving care at the Centro de Referência de Saúde da Mulher (CRSM) and at the Hospital Materno Infantil Nossa Senhora de Nazaré (HMINSN), and 167 reports were analyzed at HMINSN. Results: Most cases presented malformations of the nervous system, followed by malformations of the circulatory system and deformities of the musculoskeletal system. Cases of Down syndrome, Patau syndrome, Edwards syndrome, and rare genetic abnormalities such as Body-Stalk syndrome, Dandy-Walker syndrome and Treacher Collins syndrome have also been reported. However, despite the diagnosis of such genetic diseases, in a few cases there was a request for a chromosomal test (or other genetic test) and the result of them. Conclusion: Therefore, it is possible to conclude that despite the considerable number of live births with congenital malformations in the state, there is still a shortage with regard to the precise diagnosis and treatment of these anomalies, requiring greater allocation of resources in infrastructure and in the qualification of human resources in the region.  Introdução: A falta de oferta de atendimento especializado para malformações congênitas e um serviço de diagnóstico genético, torna difícil o registro e acompanhamento dos casos. Objetivo: Sendo assim, este trabalho visou investigar as principais anomalias genéticas que acometem os indivíduos portadores de malformações congênitas no estado de Roraima, tendo como base a consulta de prontuários e aplicações de questionários. Métodos: Foram aplicados 59 questionários para mães ou gestantes de portadores de malformações congênitas no Centro de Referência de Saúde da Mulher e no Hospital Materno Infantil Nossa Senhora de Nazaré no estado de Roraima, e analisados 167 prontuários no Hospital Materno Infantil. Resultados: A maioria dos casos apresentou malformações do sistema nervoso, afetando 75 pacientes do Hospital Materno Infantil, seguida por malformações do aparelho circulatório em 56 e deformidades do sistema digestivo em 13 casos. Também foram relatados casos de síndrome de Down, Síndrome de Patau, Síndrome de Edwards, e anomalias genéticas raras como síndrome de Body-Stalk, Síndrome de Dandy-Walker e Síndrome de Treacher Collins. Entretanto, apesar do diagnóstico de tais doenças genéticas, em poucos casos houve solicitação de exame cromossômico (ou outro teste genético) e resultado dos mesmos. Conclusão: Sendo assim, é possível concluir que apesar do número considerável de nascidos vivos com malformações congênitas no estado, ainda há uma carência no que diz respeito ao diagnóstico preciso e tratamento dessas anomalias, sendo necessário maior alocação de recursos em infraestrutura e na qualificação de recursos humanos na região

Hitomi (ASTRO-H) X-ray Astronomy Satellite

The Hitomi (ASTRO-H) mission is the sixth Japanese x-ray astronomy satellite developed by a large international collaboration, including Japan, USA, Canada, and Europe. The mission aimed to provide the highest energy resolution ever achieved at E  >  2  keV, using a microcalorimeter instrument, and to cover a wide energy range spanning four decades in energy from soft x-rays to gamma rays. After a successful launch on February 17, 2016, the spacecraft lost its function on March 26, 2016, but the commissioning phase for about a month provided valuable information on the onboard instruments and the spacecraft system, including astrophysical results obtained from first light observations. The paper describes the Hitomi (ASTRO-H) mission, its capabilities, the initial operation, and the instruments/spacecraft performances confirmed during the commissioning operations for about a month

Atrasentan and renal events in patients with type 2 diabetes and chronic kidney disease (SONAR): a double-blind, randomised, placebo-controlled trial

Background: Short-term treatment for people with type 2 diabetes using a low dose of the selective endothelin A receptor antagonist atrasentan reduces albuminuria without causing significant sodium retention. We report the long-term effects of treatment with atrasentan on major renal outcomes. Methods: We did this double-blind, randomised, placebo-controlled trial at 689 sites in 41 countries. We enrolled adults aged 18–85 years with type 2 diabetes, estimated glomerular filtration rate (eGFR)25–75 mL/min per 1·73 m 2 of body surface area, and a urine albumin-to-creatinine ratio (UACR)of 300–5000 mg/g who had received maximum labelled or tolerated renin–angiotensin system inhibition for at least 4 weeks. Participants were given atrasentan 0·75 mg orally daily during an enrichment period before random group assignment. Those with a UACR decrease of at least 30% with no substantial fluid retention during the enrichment period (responders)were included in the double-blind treatment period. Responders were randomly assigned to receive either atrasentan 0·75 mg orally daily or placebo. All patients and investigators were masked to treatment assignment. The primary endpoint was a composite of doubling of serum creatinine (sustained for ≥30 days)or end-stage kidney disease (eGFR <15 mL/min per 1·73 m 2 sustained for ≥90 days, chronic dialysis for ≥90 days, kidney transplantation, or death from kidney failure)in the intention-to-treat population of all responders. Safety was assessed in all patients who received at least one dose of their assigned study treatment. The study is registered with ClinicalTrials.gov, number NCT01858532. Findings: Between May 17, 2013, and July 13, 2017, 11 087 patients were screened; 5117 entered the enrichment period, and 4711 completed the enrichment period. Of these, 2648 patients were responders and were randomly assigned to the atrasentan group (n=1325)or placebo group (n=1323). Median follow-up was 2·2 years (IQR 1·4–2·9). 79 (6·0%)of 1325 patients in the atrasentan group and 105 (7·9%)of 1323 in the placebo group had a primary composite renal endpoint event (hazard ratio [HR]0·65 [95% CI 0·49–0·88]; p=0·0047). Fluid retention and anaemia adverse events, which have been previously attributed to endothelin receptor antagonists, were more frequent in the atrasentan group than in the placebo group. Hospital admission for heart failure occurred in 47 (3·5%)of 1325 patients in the atrasentan group and 34 (2·6%)of 1323 patients in the placebo group (HR 1·33 [95% CI 0·85–2·07]; p=0·208). 58 (4·4%)patients in the atrasentan group and 52 (3·9%)in the placebo group died (HR 1·09 [95% CI 0·75–1·59]; p=0·65). Interpretation: Atrasentan reduced the risk of renal events in patients with diabetes and chronic kidney disease who were selected to optimise efficacy and safety. These data support a potential role for selective endothelin receptor antagonists in protecting renal function in patients with type 2 diabetes at high risk of developing end-stage kidney disease. Funding: AbbVie

Adding 6 months of androgen deprivation therapy to postoperative radiotherapy for prostate cancer: a comparison of short-course versus no androgen deprivation therapy in the RADICALS-HD randomised controlled trial

Background Previous evidence indicates that adjuvant, short-course androgen deprivation therapy (ADT) improves metastasis-free survival when given with primary radiotherapy for intermediate-risk and high-risk localised prostate cancer. However, the value of ADT with postoperative radiotherapy after radical prostatectomy is unclear. Methods RADICALS-HD was an international randomised controlled trial to test the efficacy of ADT used in combination with postoperative radiotherapy for prostate cancer. Key eligibility criteria were indication for radiotherapy after radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to radiotherapy alone (no ADT) or radiotherapy with 6 months of ADT (short-course ADT), using monthly subcutaneous gonadotropin-releasing hormone analogue injections, daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as distant metastasis arising from prostate cancer or death from any cause. Standard survival analysis methods were used, accounting for randomisation stratification factors. The trial had 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 80% to 86% (hazard ratio [HR] 0·67). Analyses followed the intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov, NCT00541047. Findings Between Nov 22, 2007, and June 29, 2015, 1480 patients (median age 66 years [IQR 61–69]) were randomly assigned to receive no ADT (n=737) or short-course ADT (n=743) in addition to postoperative radiotherapy at 121 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 9·0 years (IQR 7·1–10·1), metastasis-free survival events were reported for 268 participants (142 in the no ADT group and 126 in the short-course ADT group; HR 0·886 [95% CI 0·688–1·140], p=0·35). 10-year metastasis-free survival was 79·2% (95% CI 75·4–82·5) in the no ADT group and 80·4% (76·6–83·6) in the short-course ADT group. Toxicity of grade 3 or higher was reported for 121 (17%) of 737 participants in the no ADT group and 100 (14%) of 743 in the short-course ADT group (p=0·15), with no treatment-related deaths. Interpretation Metastatic disease is uncommon following postoperative bed radiotherapy after radical prostatectomy. Adding 6 months of ADT to this radiotherapy did not improve metastasis-free survival compared with no ADT. These findings do not support the use of short-course ADT with postoperative radiotherapy in this patient population

Duration of androgen deprivation therapy with postoperative radiotherapy for prostate cancer: a comparison of long-course versus short-course androgen deprivation therapy in the RADICALS-HD randomised trial

Background Previous evidence supports androgen deprivation therapy (ADT) with primary radiotherapy as initial treatment for intermediate-risk and high-risk localised prostate cancer. However, the use and optimal duration of ADT with postoperative radiotherapy after radical prostatectomy remains uncertain. Methods RADICALS-HD was a randomised controlled trial of ADT duration within the RADICALS protocol. Here, we report on the comparison of short-course versus long-course ADT. Key eligibility criteria were indication for radiotherapy after previous radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to add 6 months of ADT (short-course ADT) or 24 months of ADT (long-course ADT) to radiotherapy, using subcutaneous gonadotrophin-releasing hormone analogue (monthly in the short-course ADT group and 3-monthly in the long-course ADT group), daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as metastasis arising from prostate cancer or death from any cause. The comparison had more than 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 75% to 81% (hazard ratio [HR] 0·72). Standard time-to-event analyses were used. Analyses followed intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov , NCT00541047 . Findings Between Jan 30, 2008, and July 7, 2015, 1523 patients (median age 65 years, IQR 60–69) were randomly assigned to receive short-course ADT (n=761) or long-course ADT (n=762) in addition to postoperative radiotherapy at 138 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 8·9 years (7·0–10·0), 313 metastasis-free survival events were reported overall (174 in the short-course ADT group and 139 in the long-course ADT group; HR 0·773 [95% CI 0·612–0·975]; p=0·029). 10-year metastasis-free survival was 71·9% (95% CI 67·6–75·7) in the short-course ADT group and 78·1% (74·2–81·5) in the long-course ADT group. Toxicity of grade 3 or higher was reported for 105 (14%) of 753 participants in the short-course ADT group and 142 (19%) of 757 participants in the long-course ADT group (p=0·025), with no treatment-related deaths. Interpretation Compared with adding 6 months of ADT, adding 24 months of ADT improved metastasis-free survival in people receiving postoperative radiotherapy. For individuals who can accept the additional duration of adverse effects, long-course ADT should be offered with postoperative radiotherapy. Funding Cancer Research UK, UK Research and Innovation (formerly Medical Research Council), and Canadian Cancer Society

Um alerta sobre teratógenos em Roraima

Teratology studies the environmental contribution in the abnormal development of the child. Teratogens are defined as any substance, organism, physical agent or state of deficiency that is present in embryonic or fetal life, produces a congenital defect. Although in the current literature there is no epidemiological survey about congenital malformations for the state of Roraima, we present here that this Amazonian space is a favorable environment for the development of these anomalies. As the state's economy is focused on agricultural and mining activities, waste from these activities, such as heavy metals and agrochemicals, routinely pollute soils and rivers and, consequently, plantations destined for animal and human consumption. In addition, some native plants, used for medicinal purposes by a large part of the roraimenses, have teratogenic potential or abortive characteristics. In addition, Roraima's own climate favors the proliferation of mosquitoes transmitting infectious agents, which are considered as teratogenic agents, such as Dengue and Zika viruses. We also highlight the risks related to the use of medications and the consumption of alcohol and tobacco during pregnancy. This article aims to alert the general population about the potential impacts caused by teratogens presente in our environment and our daily life.A teratologia estuda a contribuição ambiental no desenvolvimento anormal da criança. Já os teratógenos são definidos como qualquer substância, organismo, agente físico ou estado de deficiência que estando presente na vida embrionária ou fetal, produz um defeito congênito. Embora na literatura atual não exista um levantamento epidemiológico sobre malformações congênitas para o estado de Roraima, apresentamos aqui que esse espaço Amazônico é um ambiente favorável para o desenvolvimento dessas anomalias. Como a economia do Estado está voltada para trabalhos na área da agropecuária e mineração, os resíduos dessas atividades, como metais pesados e agrotóxicos, rotineiramente poluem os solos e rios e, consequentemente, plantações destinadas à alimentação de animais e humanos. Além disso, algumas plantas nativas, utilizadas para fins medicinais por grande parte dos roraimenses, apresentam potencial teratogênico ou características abortivas. No mais, o próprio clima de Roraima propicia a proliferação de mosquitos transmissores de agentes infecciosos, considerados como agentes teratogênicos, tais como, os vírus da Dengue e Zika. Destacamos também os riscos relacionados ao uso de medicamentos e ao consumo de álcool e fumo durante a gestação. Esse artigo visa alertar a população em geral sobre os potenciais impactos causados por teratógenos presentes em nosso ambiente e nosso cotidiano