Prognostic impact of circulating Her-2-reactive T-cells producing pro- and/or anti-inflammatory cytokines in elderly breast cancer patients

Clinico-pathological characteristics of younger and older patients. (DOCX 15 kb

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Effects of antiplatelet therapy after stroke due to intracerebral haemorrhage (RESTART): a randomised, open-label trial

Background: Antiplatelet therapy reduces the risk of major vascular events for people with occlusive vascular disease, although it might increase the risk of intracranial haemorrhage. Patients surviving the commonest subtype of intracranial haemorrhage, intracerebral haemorrhage, are at risk of both haemorrhagic and occlusive vascular events, but whether antiplatelet therapy can be used safely is unclear. We aimed to estimate the relative and absolute effects of antiplatelet therapy on recurrent intracerebral haemorrhage and whether this risk might exceed any reduction of occlusive vascular events. Methods: The REstart or STop Antithrombotics Randomised Trial (RESTART) was a prospective, randomised, open-label, blinded endpoint, parallel-group trial at 122 hospitals in the UK. We recruited adults (≥18 years) who were taking antithrombotic (antiplatelet or anticoagulant) therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage, discontinued antithrombotic therapy, and survived for 24 h. Computerised randomisation incorporating minimisation allocated participants (1:1) to start or avoid antiplatelet therapy. We followed participants for the primary outcome (recurrent symptomatic intracerebral haemorrhage) for up to 5 years. We analysed data from all randomised participants using Cox proportional hazards regression, adjusted for minimisation covariates. This trial is registered with ISRCTN (number ISRCTN71907627). Findings: Between May 22, 2013, and May 31, 2018, 537 participants were recruited a median of 76 days (IQR 29–146) after intracerebral haemorrhage onset: 268 were assigned to start and 269 (one withdrew) to avoid antiplatelet therapy. Participants were followed for a median of 2·0 years (IQR [1·0– 3·0]; completeness 99·3%). 12 (4%) of 268 participants allocated to antiplatelet therapy had recurrence of intracerebral haemorrhage compared with 23 (9%) of 268 participants allocated to avoid antiplatelet therapy (adjusted hazard ratio 0·51 [95% CI 0·25–1·03]; p=0·060). 18 (7%) participants allocated to antiplatelet therapy experienced major haemorrhagic events compared with 25 (9%) participants allocated to avoid antiplatelet therapy (0·71 [0·39–1·30]; p=0·27), and 39 [15%] participants allocated to antiplatelet therapy had major occlusive vascular events compared with 38 [14%] allocated to avoid antiplatelet therapy (1·02 [0·65–1·60]; p=0·92). Interpretation: These results exclude all but a very modest increase in the risk of recurrent intracerebral haemorrhage with antiplatelet therapy for patients on antithrombotic therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage. The risk of recurrent intracerebral haemorrhage is probably too small to exceed the established benefits of antiplatelet therapy for secondary prevention

Effects of antiplatelet therapy after stroke due to intracerebral haemorrhage (RESTART): a randomised, open-label trial

Background: Antiplatelet therapy reduces the risk of major vascular events for people with occlusive vascular disease, although it might increase the risk of intracranial haemorrhage. Patients surviving the commonest subtype of intracranial haemorrhage, intracerebral haemorrhage, are at risk of both haemorrhagic and occlusive vascular events, but whether antiplatelet therapy can be used safely is unclear. We aimed to estimate the relative and absolute effects of antiplatelet therapy on recurrent intracerebral haemorrhage and whether this risk might exceed any reduction of occlusive vascular events. Methods: The REstart or STop Antithrombotics Randomised Trial (RESTART) was a prospective, randomised, open-label, blinded endpoint, parallel-group trial at 122 hospitals in the UK. We recruited adults (≥18 years) who were taking antithrombotic (antiplatelet or anticoagulant) therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage, discontinued antithrombotic therapy, and survived for 24 h. Computerised randomisation incorporating minimisation allocated participants (1:1) to start or avoid antiplatelet therapy. We followed participants for the primary outcome (recurrent symptomatic intracerebral haemorrhage) for up to 5 years. We analysed data from all randomised participants using Cox proportional hazards regression, adjusted for minimisation covariates. This trial is registered with ISRCTN (number ISRCTN71907627). Findings: Between May 22, 2013, and May 31, 2018, 537 participants were recruited a median of 76 days (IQR 29–146) after intracerebral haemorrhage onset: 268 were assigned to start and 269 (one withdrew) to avoid antiplatelet therapy. Participants were followed for a median of 2·0 years (IQR [1·0– 3·0]; completeness 99·3%). 12 (4%) of 268 participants allocated to antiplatelet therapy had recurrence of intracerebral haemorrhage compared with 23 (9%) of 268 participants allocated to avoid antiplatelet therapy (adjusted hazard ratio 0·51 [95% CI 0·25–1·03]; p=0·060). 18 (7%) participants allocated to antiplatelet therapy experienced major haemorrhagic events compared with 25 (9%) participants allocated to avoid antiplatelet therapy (0·71 [0·39–1·30]; p=0·27), and 39 [15%] participants allocated to antiplatelet therapy had major occlusive vascular events compared with 38 [14%] allocated to avoid antiplatelet therapy (1·02 [0·65–1·60]; p=0·92). Interpretation: These results exclude all but a very modest increase in the risk of recurrent intracerebral haemorrhage with antiplatelet therapy for patients on antithrombotic therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage. The risk of recurrent intracerebral haemorrhage is probably too small to exceed the established benefits of antiplatelet therapy for secondary prevention

Effects of antiplatelet therapy after stroke due to intracerebral haemorrhage (RESTART): a randomised, open-label trial

BACKGROUND: Antiplatelet therapy reduces the risk of major vascular events for people with occlusive vascular disease, although it might increase the risk of intracranial haemorrhage. Patients surviving the commonest subtype of intracranial haemorrhage, intracerebral haemorrhage, are at risk of both haemorrhagic and occlusive vascular events, but whether antiplatelet therapy can be used safely is unclear. We aimed to estimate the relative and absolute effects of antiplatelet therapy on recurrent intracerebral haemorrhage and whether this risk might exceed any reduction of occlusive vascular events. METHODS: The REstart or STop Antithrombotics Randomised Trial (RESTART) was a prospective, randomised, open-label, blinded endpoint, parallel-group trial at 122 hospitals in the UK. We recruited adults (≥18 years) who were taking antithrombotic (antiplatelet or anticoagulant) therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage, discontinued antithrombotic therapy, and survived for 24 h. Computerised randomisation incorporating minimisation allocated participants (1:1) to start or avoid antiplatelet therapy. We followed participants for the primary outcome (recurrent symptomatic intracerebral haemorrhage) for up to 5 years. We analysed data from all randomised participants using Cox proportional hazards regression, adjusted for minimisation covariates. This trial is registered with ISRCTN (number ISRCTN71907627). FINDINGS: Between May 22, 2013, and May 31, 2018, 537 participants were recruited a median of 76 days (IQR 29-146) after intracerebral haemorrhage onset: 268 were assigned to start and 269 (one withdrew) to avoid antiplatelet therapy. Participants were followed for a median of 2·0 years (IQR [1·0- 3·0]; completeness 99·3%). 12 (4%) of 268 participants allocated to antiplatelet therapy had recurrence of intracerebral haemorrhage compared with 23 (9%) of 268 participants allocated to avoid antiplatelet therapy (adjusted hazard ratio 0·51 [95% CI 0·25-1·03]; p=0·060). 18 (7%) participants allocated to antiplatelet therapy experienced major haemorrhagic events compared with 25 (9%) participants allocated to avoid antiplatelet therapy (0·71 [0·39-1·30]; p=0·27), and 39 [15%] participants allocated to antiplatelet therapy had major occlusive vascular events compared with 38 [14%] allocated to avoid antiplatelet therapy (1·02 [0·65-1·60]; p=0·92). INTERPRETATION: These results exclude all but a very modest increase in the risk of recurrent intracerebral haemorrhage with antiplatelet therapy for patients on antithrombotic therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage. The risk of recurrent intracerebral haemorrhage is probably too small to exceed the established benefits of antiplatelet therapy for secondary prevention. FUNDING: British Heart Foundation

Prognostic impact of high levels of circulating plasmacytoid dendritic cells in breast cancer

Additional file 2: Table S1. Patients clinico-pathological parameters

Prognostic impact of high levels of circulating plasmacytoid dendritic cells in breast cancer

Abstract Background Identifying immune markers in blood that are informative for breast cancer patient survival would not only be useful for prognosis but might also provide mechanistic insights into processes facilitating survival. Methods We phenotyped circulating plasmacytoid dendritic cells (pDCs), myeloid-derived suppressor cells (MDSCs) and regulatory T-cells in relation to T-cell responses to Her-2 in vitro in 75 untreated breast cancer patients 28–87 years of age at diagnosis. Results Patients with later stage tumors had lower levels of circulating pDCs (p = 0.008). There was a positive association between 5-year survival and higher than median levels of circulating pDCs (p = 0.03). We confirmed that 5-year survival correlated with CD8+ but not CD4+ T-cell responsiveness to Her-2 peptides in this cohort of younger and older patients (p = 0.04). Including pDCs in the analysis of previously-established parameters revealed that patients who had a CD8+ T-cell response to Her-2 together with a low ratio of MDSCs:pDCs had 100 % 5-year survival. High levels of pDCs and the presence of a CD8+ T-cell response to Her-2 were independent positive survival indicators according to multivariate Cox analysis. Conclusions Our new results suggest that circulating pDCs could be a positive prognostic indicator in breast cancer patients of all ages, together with the previously established CD8+ T-cell reactivity to Her-2 antigens in older patients only. These two prognostic indicators were independent and emphasize the important role of immunity in ensuring breast cancer patient survival, even in those not undergoing immunotherapy

Situation analysis for delivering integrated comprehensive sexual and reproductive health services for displaced population of Kasaï, Democratic Republic of Congo: Protocol for a mixed method study.

IntroductionDelivering integrated sexual and reproductive health services (SRHS) in emergencies is important in order to save lives of the most vulnerable as well as to combat poverty, reduce inequities and social injustice. More than 60% of preventable maternal deaths occur in conflict areas and especially among the internally displaced persons (IDP). Between 2016 and 2018, unprecedented violence erupted in the Kasaï's region, in the Democratic Republic of Congo (DRC), called the Kamuina Nsapu Insurgency. During that period, an estimated three million of adolescent girls and women were forced to flee; and have faced growing threat to their health, safety, security, and well-being including significant sexual and reproductive health challenges. Between August 2016 and May 2017, the "Sous-Cluster sur les violences basées sur le genre (SC-VBG)" in DRC (2017) reported 1,429 Gender Based Violence (GBV) incidents in the 49 service delivery points in the provinces of Kasaï, Kasaï Central and Kasaï Oriental. Rape cases represented 79% of reported incidents whereas sexual assault and forced marriage accounted for respectively 11% and 4% of Gender Based Violence (GBV) among women and adolescent girls. This study aims to assess the availability of SRHS in the displaced camps in Kasaï; to evaluate the SRHS needs of young girls and women in the reproductive age (12-49). Studies of sexual and reproductive health (SRH) in the Democratic Republic of Congo (DRC) have often included adolescent girls under the age of 15 because of high prevalence of child marriage and early onset of childbearing, especially in the humanitarian context. According to the 2013 Demographic and Health Survey (DHS), about 16% of surveyed women got married by age 14 while the prevalence of early child marriage (marriage by 15) was estimated at 30%; to assess the use of SRHS services and identify barriers as well as challenges for SRH service delivery and use. Findings from this study will help provide evidence to inform towards more needs-based and responsive SRH service delivery. This is hoped for ultimately improve the quality and effectiveness of services, when considering service delivery and response in humanitarian settings.Data and methodsWe will conduct a mixed-methods study design, which will combine quantitative and qualitative approaches. Based on the estimation of the sample size, quantitative data will be drawn from the community-based survey (500 women of reproductive age per site) and health facility assessments will include assessments of 45 health facilities and 135 health providers' interviews. Qualitative data will comprise materials from 30 Key Informant Interviews (KII) and 24 Focus Group Discussions (FGDs), which are believed to achieve the needed saturation levels. Data analysis will include thematic and content analysis for the KIIs and FGDs using ATLAS.ti software for the qualitative arm. For the quantitative arm, data analysis will combine frequency and bivariate chi-square analysis, coupled with multi-level regression models, using Stata 15 software. Statistic differences will be established at the significance level of 0.05. We submitted this protocol to the national ethical committee of the ministry of health in September 2019 and it was approved in January 2020. It needs further approval from the Scientific Oversee Committee (SOC) and the Provincial Ministry of Health. Prior to data collection, informed consents will be obtained from all respondents

Additional file 1: of Participatory action research to identify a package of interventions to promote postpartum family planning in Burkina Faso and the Democratic Republic of Congo

Appointment card for women. (PPTX 100 kb