Is the profile of transcripts altered in the eutopic endometrium of infertile women with endometriosis during the implantation window?

STUDY QUESTION: Compared to healthy women, is the profile of transcripts altered in the eutopic endometrium of infertile women with endometriosis during the implantation window (IW)? SUMMARY ANSWER: The eutopic endometrium of infertile women with endometriosis seems to be transcriptionally similar to the endometrium of infertile and fertile controls (FC) during the IW. WHAT IS KNOWN ALREADY: Endometriosis is a disease related to infertility; nevertheless, little is known regarding the ethiopathogenic mechanisms underlying this association. Some studies evaluating the eutopic endometrium of endometriosis patients suggest there is an endometrial factor involved in the disease-related infertility. However, no study to date has evaluated the endometrial transcriptome (mRNA and miRNA) by next generation sequencing (NGS), comparing patients with endometriosis as the exclusive infertility factor (END) to infertile controls (IC; male and/or tubal factor) and FC. STUDY DESIGN, SIZE, DURATION: From November 2011 to November 2015 we performed a case-control study, where 17 endometrial samples (six END, six IC, five FC) were collected during the IW. PARTICIPANTS/MATERIALS, SETTING, METHODS: All endometrial samples had the RNA extracted. Two libraries were prepared for each one (mRNA and miRNA), which were sequenced, respectively, at HISEQ 2500 (RNA-Seq) and MiSeq System (miRNA-Seq), Illumina. The normalization and differential expression were conducted in statistical R environment using DESeq2 package. qPCR was used for data validation, which were analyzed by Kruskal-Wallis test and Dunn posttest (P < 0.05). MAIN RESULTS AND THE ROLE OF CHANCE: RNA-Seq revealed no differentially expressed genes (DEG) among END, IC and FC groups. miRNA-Seq revealed three differentially expressed miRNAs (has-27a-5p, has-miR-150-5p, has-miR-504-5p) in END group compared to FC group. However, none of the miRNAs identified in the sequencing was validated by qPCR. LIMITATIONS, REASONS FOR CAUTION: The main limitation of this study was the small sample size evaluated as a result of the restrictive eligibility criteria adopted, limiting the generalization of the results obtained here. On the other hand, strict eligibility criteria, which eliminated factors potentially related to impaired endometrial receptivity, were required to increase the study's internal validity. WIDER IMPLICATIONS OF THE FINDINGS: This study brings new perspectives on the mechanisms involved in endometriosis-related infertility. The present findings suggest the eutopic endometrium of infertile women with endometriosis, without considering the disease's stage, is transcriptionally similar to controls during the IW, possibly not affecting receptivity. Further studies are needed to evaluate endometrial alterations related to endometriosis' stages. STUDY FUNDING/COMPETING INTEREST(S): This study received financial support from the Sao Paulo Research Foundation (FAPESP-Fundação de Amparo à Pesquisa do Estado de São Paulo; fellowship 2011/17614-6, MGB) and from the National Council for Scientific and Technological Development (CNPq-Conselho Nacional de Desenvolvimento Científico e Tecnológico; INCT-National Institutes of Hormones and Woman's Health, grant 471 943/2012-6, 309 397/2016-2, PAN; fellowship 140 137/2015-7, MGB). The authors have no conflicts of interest. TRIAL REGISTRATION NUMBER: N/A.

Reporting Clinical End Points and Safety Events in an Acute Coronary Syndrome Trial: Results With Integrated Collection.

BACKGROUND: End points and adverse events (AEs) are collected separately in clinical trials, yet regulatory requirements for serious AE reporting vary across regions, so classifying end points according to seriousness criteria can be useful in global trials. METHODS AND RESULTS: In the Apixaban for Prevention of Acute Ischemic Events 2 (APPRAISE-2) trial, patients with a recent acute coronary syndrome were randomized to apixaban or placebo for the prevention of recurrent ischemic events. Suspected end points (myocardial infarction, stroke, or bleeding) were adjudicated by an independent clinical events classification committee. Safety criteria were collected for suspected end points and AEs. Patient-level event rates per 100 patient-days of follow-up, modeled using Poisson regression, explored the influence of region and patient characteristics on event reporting. Overall, 13 909 events were reported by 858 sites in 39 countries; 8.4% (n=1166) were suspected end points, and 91.6% (n=12 743) were AEs. Overall, 66.0% of suspected end points were confirmed by the clinical events classification committee. Most clinical events classification committee-confirmed end points met criteria to be classified as serious (94.0%); many clinical events classification committee-negated end points also did (63.2%), but fewer AEs met seriousness criteria (17.9%). The most common seriousness criterion was hospitalization (79.9%, n=2594). Region explained 28.7% of end point- and 26.4% of serious AE-reporting variation, and patient characteristics explained an additional 25.4% of end point and 13.4% of serious AE variation. Nonserious AE-reporting variation was not explained by adjustment. CONCLUSIONS: An integrated collection of end points and serious AEs is feasible in a multinational trial and illustrates the shared characteristics of events. Tailoring event collection to fit the phase and purpose of the trial is achievable and informative. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00831441.

[Left ventricular pseudoaneurysm associated to severe mitral insufficiency, complicating inferolaterodorsal acute myocardial infarction]. / Pseudoaneurisma de ventrículo esquerdo associado a insuficiência mitral grave complicando infarto agudo do miocárdio ínfero-látero-dorsal.

We described a case of left ventricular pseudoaneurysm associated to a severe mitral regurgitation, complicating a inferolaterodorsal acute myocardial infarction. The lesion was found in a routine echocardiogram during the in-hospital follow-up. The well-succeeded surgical strategy and the good clinical evolution of the patient were distinguished.

Pseudoaneurisma de ventrículo esquerdo associado a insuficiência mitral grave complicando infarto agudo do miocárdio ínfero-látero-dorsal / Left ventricular pseudoaneurysm associated to severe mitral insufficiency, complicating inferolaterodorsal acute myocardial infarction

Descrevemos um caso de pseudoaneurisma de ventrículo esquerdo associado a grave regurgitacão mitral, complicando um infarto ínfero-látero-dorsal. A lesão foi descoberta em ecocardiograma de rotina durante o seguimento ambulatorial. Destacam-se a estratégia cirúrgica bem sucedida, e a boa evolucão clínica da paciente.

Futuro da fibrinólise no infarto agudo do miocárdio: fibrinolíticos de terceira geração e associação com inibidores da glicoproteína IIb/IIIa / New perspectives in fibrinolysis: third generation thrombolytics and platelet glycoprotein IIb/IIIa inhibitors

A terapêutica fibrinolítica demonstrou, ao longo dos últimos anos, melhorar a sobrevida a curto e longo prazos em portadores de infarto agudo do miocárdio com supradesnível do segmento ST. A despeito de seu benefício, o insucesso dos agentes tradicionais, como estreptoquinase e ativador do plasminogênio tecidual (t-PA), em alcançar fluxos coronarianos máximos precipitou a busca por trombolíticos mais eficientes. A maior parte desses novos agentes de terceira geração, desenvolvidos por engenharia genética a partir do t-PA, foi testada em estudos clínicos e apresentou resultados equivalentes aos obtidos com o t-PA. Assim, a reteplase, o TNK-t-PA e a lanoteplase demonstraram mortalidade e complicações hemorrágicas similares ao t-PA. A introdução de novos conceitos sobre a fisiopatologia da formação do trombo nas síndromes isquêmicas miocárdicas instáveis levou à associação de agentes fibrinolíticos com potentes bloqueadores plaquetários. Essa associação traz novas esperanças para o tratamento do infarto do miocárdio.

Choque cardiogenico: sugestao para o racional da terapeutica do infarto agudo do miocardio / Cardiogenic shock: suggestion to rational treatment after myocardial infarction

O choque cardiogenico e uma condicao critica que deve ser prontamente abordada de forma efetiva e coordenada. desta maneira, seu curso natural, habitualmente catastrofico, pode ser revertido. Os objetos principais a serem alcancados com este proposito sao a manutencao da prefusao dos orgaos vitais (etapa I) e reperfusao precoce da area sob risco, unica capaz de alterar o prognostico destes doentes (etapa II). De acordo com criterios anatomo-funcionais de classificacao (choque por acometimento predominante de ventriculo direito, esquerdo ou mecanico) sao propostas as fases a serem cumpridas em cada etapa