Avaliação da prescrição e do uso de anticoncepção em mulheres com diabetes mellitus

O Diabetes Mellitus (DM) é um importante problema de saúde pública. Planejar a gestação da mulher com DM tem uma grande importância, uma vez que a garantia de uma gestação saudável e de feto viável depende de níveis glicêmicos adequados, além de outros cuidados de saúde. A presente dissertação teve os seguintes objetivos: avaliar a adequação do registro em prontuário de uso de métodos anticoncepcionais (MAC) por pacientes com DM em idade fértil e identificar quais fatores estão associados com a ausência de registro desses medicamentos; descrever os MAC utilizados por pacientes com DM e se a prescrição está de acordo com os critérios de elegibilidade da Organização Mundial de Saúde (OMS). Foi realizado um estudo transversal com revisão de 1.069 prontuários de mulheres com DM atendidas no Hospital de Clínicas de Porto Alegre (HCPA) entre janeiro de 2019 e junho de 2019. Destas, 313 estavam em idade fértil e foram incluídas no estudo, sendo o registro de uso de MAC encontrado em 173 (55,3%) dos prontuários. Na segunda fase do estudo, 270 mulheres, dentre as arroladas, foram entrevistadas. Destas, 201 (74,4%) relataram usar algum MAC. Das 69 (25,6%) que não estavam em uso, 18 não estavam em risco de gestação devido à infertilidade (n = 14) ou relação homossexual (n = 4), restando 51 pacientes férteis com DM em risco de uma gestação não planejada (18,9% do total de entrevistadas). Os métodos mais usados foram os hormonais por via oral (combinado em 34,3% e progesterona isolada em 17,9%). No que diz respeito às contraindicações, 67 (33,3%) mulheres estavam usando método inadequado, ou seja, classificado como categoria 3 ou 4 da OMS para sua condição clínica. Em conclusão, um terço das mulheres com DM em acompanhamento no serviço de endocrinologia de um hospital universitário estão em idade fértil. A ausência de registro de uso de MAC no prontuário de quase metade das participantes sugere que esta abordagem não tem sido realizada, especialmente nas pacientes com mais de 40 anos, cor não branca auto relatada e escolaridade ≤ 11 anos de estudo. O MAC mais utilizado foi o anticoncepcional hormonal combinado. Devido aos riscos de uma gestação em mulheres com DM não compensado, métodos com maior efetividade como o dispositivo/sistema intrauterino ou implante deveriam ser mais recomendados, especialmente em adolescentes e mulheres jovens. Aproximadamente um terço das entrevistadas estava usando MAC inadequado para a sua condição clínica e um quinto estava em risco de uma gestação sem planejamento adequado. Tendo como base esses resultados, melhorias no planejamento familiar de mulheres com DM devem ser instituídas

Intramyocardial Sprouting Tip Cells Specify Coronary Arterialization.

The elaborate patterning of coronary arteries critically supports the high metabolic activity of the beating heart. How coronary endothelial cells coordinate hierarchical vascular remodeling and achieve arteriovenous specification remains largely unknown. Understanding the molecular and cellular cues that pattern coronary arteries is crucial to develop innovative therapeutic strategies that restore functional perfusion within the ischemic heart. Results: We discover that coronary arteries originate from cells that have previously transitioned through a specific tip cell phenotype. We identify nonoverlapping intramyocardial and subepicardial tip cell populations with differential gene expression profiles and regulatory pathways. Esm1-lineage tracing confirmed that intramyocardial tip cells selectively contribute to coronary arteries and endocardial tunnels, but not veins. Notably, prearterial cells are detected from development stages to adulthood, increasingly in response to ischemic injury, and in human embryos, suggesting that tip cell-to-artery specification is a conserved mechanism. Conclusions: A tip cell-to-artery specification mechanism drives arterialization of the intramyocardial plexus and endocardial tunnels throughout life and is reactivated upon ischemic injury. Differential sprouting programs govern the formation and specification of the venous and arterial coronary plexus.This project was supported by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation, SFB1366—B06 and SFB1470—A04) and by the Deutsches Zentrum für Herz-Kreislauf-Forschung (DZHK; German Center for Cardiovascular Research). E. Cano was also supported by a Postdoctoral Fellowship from Ramon Areces Foundation

Impact of daclizumab, low-dose cyclosporine, mycophenolate mofetil and steroids on renal function after kidney transplantation

Background. Early and long-term use of cyclosporine A (CsA) leads to increased risks of renal toxicity. We hypothesized that administration of daclizumab in combination with mycophenolate mofetil (MMF) allows a relevant reduction in the dose of CsA. Methods. We carried out a 3-year, prospective, randomized, controlled clinical multi-centre trial in 156 patients. The patients were randomized to standard treatment (CsA, MMF, steroids) or to high-dose daclizumab (first dose: 2 mg/kg), in combination with low-dose CsA, MMF and steroids. We maintained the mean CsA levels of daclizumab patients at 57% of standard patients (132 versus 216 ng/ml) on Day 7 post-transplant, and 84% by 6 months. Results. Primary outcome, creatinine clearance (with imputation of informative dropouts) at 12 months, was significantly better in daclizumab-treated (34 ± 17) than standard patients (29 ± 17; P = 0.028, two sided). Only 5 cases of BPAR were recorded in the daclizumab compared to 22 in the standard group (P = 0.0016). Daclizumab patients had 91% event-free survival after 1 year compared to 66% in standard patients (P = 0.00017). Conclusion. We demonstrate here that high-dose daclizumab in combination with lower CsA levels in adult renal transplant recipients is as or more effective than standard regimen (CsA, MMF, steroids) and may result in better outcomes at 12 months post-transplant with no increase in adverse reaction

The ReIMAGINE prostate cancer risk study protocol: A prospective cohort study in men with a suspicion of prostate cancer who are referred onto an MRI-based diagnostic pathway with donation of tissue, blood and urine for biomarker analyses

INTRODUCTION: The ReIMAGINE Consortium was conceived to develop risk-stratification models that might incorporate the full range of novel prostate cancer (PCa) diagnostics (both commercial and academic). METHODS: ReIMAGINE Risk is an ethics approved (19/LO/1128) multicentre, prospective, observational cohort study which will recruit 1000 treatment-naive men undergoing a multi-parametric MRI (mpMRI) due to an elevated PSA (≤20ng/ml) or abnormal prostate examination who subsequently had a suspicious mpMRI (score≥3, stage ≤T3bN0M0). Primary outcomes include the detection of ≥Gleason 7 PCa at baseline and time to clinical progression, metastasis and death. Baseline blood, urine, and biopsy cores for fresh prostate tissue samples (2 targeted and 1 non-targeted) will be biobanked for future analysis. High-resolution scanning of pathology whole-slide imaging and MRI-DICOM images will be collected. Consortium partners will be granted access to data and biobanks to develop and validate biomarkers using correlation to mpMRI, biopsy-based disease status and long-term clinical outcomes. RESULTS: Recruitment began in September 2019(n = 533). A first site opened in September 2019 (n = 296), a second in November 2019 (n = 210) and a third in December 2020 (n = 27). Acceptance to the study has been 65% and a mean of 36.5ml(SD+/-10.0), 12.9ml(SD+/-3.7) and 2.8ml(SD+/-0.7) urine, plasma and serum donated for research, respectively. There are currently 4 academic and 15 commercial partners spanning imaging (~9 radiomics, artificial intelligence/machine learning), fluidic (~3 blood-based and ~2urine-based) and tissue-based (~1) biomarkers. CONCLUSION: The consortium will develop, or adjust, risk models for PCa, and provide a platform for evaluating the role of novel diagnostics in the era of pre-biopsy MRI and targeted biopsy

Forward and backward diffraction radiation of relativistic electrons in a dielectric targets

BACKGROUND: Early and long-term use of cyclosporine A (CsA) leads to increased risks of renal toxicity. We hypothesized that administration of daclizumab in combination with mycophenolate mofetil (MMF) allows a relevant reduction in the dose of CsA. METHODS: We carried out a 3-year, prospective, randomized, controlled clinical multi-centre trial in 156 patients. The patients were randomized to standard treatment (CsA, MMF, steroids) or to high-dose daclizumab (first dose: 2 mg/kg), in combination with low-dose CsA, MMF and steroids. We maintained the mean CsA levels of daclizumab patients at 57% of standard patients (132 versus 216 ng/ml) on Day 7 post-transplant, and 84% by 6 months. RESULTS: Primary outcome, creatinine clearance (with imputation of informative dropouts) at 12 months, was significantly better in daclizumab-treated (34 +/- 17) than standard patients (29 +/- 17; P = 0.028, two sided). Only 5 cases of BPAR were recorded in the daclizumab compared to 22 in the standard group (P = 0.0016). Daclizumab patients had 91% event-free survival after 1 year compared to 66% in standard patients (P = 0.00017). CONCLUSION: We demonstrate here that high-dose daclizumab in combination with lower CsA levels in adult renal transplant recipients is as or more effective than standard regimen (CsA, MMF, steroids) and may result in better outcomes at 12 months post-transplant with no increase in adverse reactions