Genome-Wide Association Study in BRCA1 Mutation Carriers Identifies Novel Loci Associated with Breast and Ovarian Cancer Risk

BRCA1-associated breast and ovarian cancer risks can be modified by common genetic variants. To identify further cancer risk-modifying loci, we performed a multi-stage GWAS of 11,705 BRCA1 carriers (of whom 5,920 were diagnosed with breast and 1,839 were diagnosed with ovarian cancer), with a further replication in an additional sample of 2,646 BRCA1 carriers. We identified a novel breast cancer risk modifier locus at 1q32 for BRCA1 carriers (rs2290854, P = 2.7×10-8, HR = 1.14, 95% CI: 1.09-1.20). In addition, we identified two novel ovarian cancer risk modifier loci: 17q21.31 (rs17631303, P = 1.4×10-8, HR = 1.27, 95% CI: 1.17-1.38) and 4q32.3 (rs4691139, P = 3.4×10-8, HR = 1.20, 95% CI: 1.17-1.38). The 4q32.3 locus was not associated with ovarian cancer risk in the general population or BRCA2 carriers, suggesting a BRCA1-specific associat

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Tratamento da leishmaniose mucosa com sulfato de aminosidine: resultados de dois anos de acompanhamento

Em 1996 foram avaliados clinicamente 20 dos 21 pacientes com leishmaniose mucosa, tratados em 1994 com sulfato de aminosidine 16mg do sal/kg/dia, intramuscular, por 20 dias. Um paciente foi a óbito por causas não relacionadas com a leishmaniose mucosa. Dos 14 pacientes (66,7% N = 21) que inicialmente alcançaram a remissão completa dos sinais e sintomas durante os três primeiros meses de seguimento, sete (50% N = 14) permaneceram livres de doença por 24 meses e sete pacientes apresentaram recidiva neste período. O acompanhamento sorológico mostrou pobre correlação com a avaliação clínica

Estudo terapêutico aberto com sulfato de aminosidine na leishmaniose mucosa causada for Leishmania (viannia) braziliensis

No período de setembro a novembro de 1994 foram tratados 21 pacientes com leishmaniose mucosa ativa, predominantemente adultos lavradores do sexo masculino, com sulfato de aminosidine intramuscular, I6mg/kg/dia por 20 dias. Treze pacientes eram virgens de tratamento e 8 haviam sido tratados sem sucesso com Glucantime®". O diagnóstico baseou-se inicialmente em crítêrios epidemiolôgicos, clínicos e nos resultados da intrademoireação de Montenegro e a imunofluorescência indireta para anticoipos séricos antileishmânia e durante o acompanhamento nos resultados dos estudos parasitológicos. Sessenta e sete por cento dos pacientes tiveram diagnóstico parasitológico confirmado sendo a inoculação do material de biópsia das lesões em hamsters o método mais sensível. O tempo médio de acompanhamento foi de 12,6 meses. A adesão ao tratamento foi de 100%. Os efeitos colaterais foram dor no local da injeção (86%), proteinúria leve (24%), elevação do nível sérico de creatinina (5%) e perda auditiva subclínica em um dos dois pacientes que realizaram audiometria. Obsevou-se cura clínica em 48% dos pacientes e a percentagem acumulada de recidiva foi de 29% (4/14pacientes) durante o acompanhamento.<br>From September to November 1994, 21 patients with active mucosal leishmaniasis were treated with aminosidine sulphate I6mg/kg/day by intramuscular injection for 20 days. They were principally adult male agricultural workers. Thirteen patients had not received specific treatment and eight had failed to respond to Glucantime® therapy. Diagnosis was based on clinical and epidemiological observations, a search for the parasite, leishmanin skin sensitivity and indirect fluorescent antibody serological tests. Sixty seven percent of patients had Leishmania parasites isolated from inoculated hamsters or visualized in imprints or histopathological sections. The mean follow-up period was 12.6 months. All patients completed treatment. Side effects were pain at the injection site (86%), mild proteinuria (24%), elevated serum creatinine (5%) and subclinical hearing loss in one of two patients who did audiometric tests. Clinical cure was achieved in 48% and the accumulated relapse rate was 29% (4/14)

Pulmonary thromboembolism in AIDS patient with chronic venous insufficiency, pulmonary tuberculosis and breast cancer: a case report and pathophysiology review Tromboembolismo pulmonar em uma paciente com AIDS com insuficiência venosa profunda, tuberculose pulmonar e câncer de mama: relato de um caso e revisão da fisiopatologia

Recent literature reports thrombotic episodes occurring in patients with HIV infection associated with other abnormalities including neoplasms and infections predisposing to a hypercoagulable state. We report a 47-year-old woman who developed pulmonary thromboembolism in association with HIV infection, pulmonary tuberculosis and breast cancer. She was treated with rifampin, isoniazid, pyrazinamide; heparin, phenprocoumon, zidovudine, lamivudine and efavirenz. Acid fast bacilli were visualized in a sputum smear and three months after, Mycobacterium tuberculosis was isolated from lymph node biopsy during a episode of immune reconstitution. The isolated mycobacteria showed sensitivity to all first-line drugs. HIV infection, breast cancer and pulmonary tuberculosis have several mechanisms that induce hypercoagulable state and can lead to thromboembolic complications. Pulmonary thromboembolism in this patient was a diagnostic challenge because of all the other severe diseases that she experienced at the same time.<br>Publicações recentes relatam episódios trombóticos em pacientes infectados pelo HIV associados a outras condições que incluem neoplasias e infecções que predispõem para um estado de hipercoagulabilidade. Relata-se o caso de uma paciente de 47 anos portadora do HIV que desenvolveu tromboembolismo pulmonar, tuberculose pulmonar e câncer de mama. Foi tratada com rifampicina, isoniazida, pirazinamida, heparina, femprocumona, zidovudina, lamivudina e efavirenz. Bacilos ácido-álcool-resistentes foram observados no exame de escarro e três meses depois foi isolado o Mycobacterium tuberculosis da biópsia de linfonodo durante um episódio de reconstituição imune. A micobactéria isolada demonstrou sensibilidade a todas as drogas anti-tuberculosas de primeira linha. A infecção pelo HIV, o câncer de mama e a tuberculose pulmonar possuem vários mecanismos que induzem um estado de hipercoagulabilidade e que podem produzir complicações tromboembólicas incluindo o TEP nos pacientes com AIDS. O TEP nesta paciente foi um desafio diagnóstico, considerando todas as outras doenças graves que apresentou simultaneamente