Paris Descartes University

About: Paris Descartes University is a government organization based out in Paris, France. It is known for research contribution in the topics: Population & Immune system. The organization has 20987 authors who have published 37456 publications receiving 1206222 citations. The organization is also known as: Université Paris V-Descartes & Université de Paris V.

Activating autophagy to potentiate immunogenic chemotherapy and radiation therapy

Abstract: Autophagy is fundamental to the maintenance of intracellular homeostasis in virtually all human cells. Accordingly, defective autophagy predisposes healthy cells to undergoing malignant transformation. By contrast, malignant cells are able to harness autophagy to thrive, despite adverse microenvironmental conditions, and to resist therapeutic challenges. Thus, inhibition of autophagy has been proposed as a strategy to kill cancer cells or sensitize them to therapy; however, autophagy is also critical for optimal immune function, and mediates cell-extrinsic homeostatic effects owing to its central role in danger signalling by neoplastic cells responding to immunogenic chemotherapy and/or radiation therapy. In this Perspective, we discuss accumulating preclinical and clinical evidence in support of the all-too-often dismissed possibility that activating autophagy might be a relevant clinical objective that enables an increase in the effectiveness of immunogenic chemotherapy and/or radiation therapy.

Improving care for patients with acute heart failure: before, during and after hospitalization

Abstract: Acute heart failure (AHF) is a common and serious condition that contributes to about 5% of all emergency hospital admissions in Europe and the USA. Here, we present the recommendations from structured discussions among an author group of AHF experts in 2013. The epidemiology of AHF and current practices in diagnosis, treatment, and long-term care for patients with AHF in Europe and the USA are examined. Available evidence indicates variation in the quality of care across hospitals and regions. Challenges include the need for rapid diagnosis and treatment, the heterogeneity of precipitating factors, and the typical repeated episodes of decompensation requiring admission to hospital for stabilization. In hospital, care should involve input from an expert in AHF and auditing to ensure that guidelines and protocols for treatment are implemented for all patients. A smooth transition to follow-up care is vital. Patient education programmes could have a dramatic effect on improving outcomes. Information technology should allow, where appropriate, patient telemonitoring and sharing of medical records. Where needed, access to end-of-life care and support for all patients, families, and caregivers should form part of a high-quality service. Eight evidence-based consensus policy recommendations are identified by the author group: optimize patient care transitions, improve patient education and support, provide equity of care for all patients, appoint experts to lead AHF care across disciplines, stimulate research into new therapies, develop and implement better measures of care quality, improve end-of-life care, and promote heart failure prevention.

Evaluation of prothrombin complex concentrate and recombinant activated factor VII to reverse rivaroxaban in a rabbit model.

Abstract: BACKGROUND As a potent anticoagulant agent, rivaroxaban exposes a risk of bleeding. An effective way to reverse its effects is needed. Objectives were to study efficacy and safety of recombinant activated factor VII (rFVIIa) and prothrombin complex concentrate (PCC) to reverse the anticoagulant effect of an overdose of rivaroxaban in a rabbit model of bleeding and thrombosis. METHODS First, a dose-ranging study assessed the minimal rivaroxaban dose that increased bleeding. Then, 48 anesthetized and ventilated rabbits were randomized into four groups: control (saline), rivaroxaban (rivaroxaban and saline), rFVIIa (rivaroxaban and rFVIIa), and PCC (rivaroxaban and PCC). The Folts model was applied: a stenosis and an injury were carried out on the carotid artery, inducing thrombosis, detected as cyclic flow reductions, which were recorded over 20 min. Then the following were measured: ear immersion bleeding time, clotting times, anti-Xa activity, thrombelastometric parameters, and thrombin generation test. Ultimately, a hepatosplenic section was performed and the total amount of blood loss after 15 min was evaluated as primary endpoint. RESULTS Rivaroxaban increased blood loss (17 g [8-32] vs. 7 g [5-18] for control (median [range]), P = 0.0004), ear bleeding time, clotting times, thrombelastographic clotting time, and decreased thrombin generation. In contrast, rFVIIa decreased ear bleeding time (92 s [65-115] vs. 140 s [75-190], P < 0.02), but without efficacy on blood loss. PCC and rFVIIa decreased activated partial thromboplastin time as well as thrombelastographic clotting time. Regarding safety, neither rFVIIa nor PCC increased cyclic flow reductions. CONCLUSION rFVIIa and PCC partially improved laboratory parameters, but did not reverse rivaroxaban induced-bleeding.

Prevention of Psychosis: Advances in Detection, Prognosis, and Intervention

Abstract: Importance Detection, prognosis, and indicated interventions in individuals at clinical high risk for psychosis (CHR-P) are key components of preventive psychiatry. Objective To provide a comprehensive, evidence-based systematic appraisal of the advancements and limitations of detection, prognosis, and interventions for CHR-P individuals and to formulate updated recommendations. Evidence Review Web of Science, Cochrane Central Register of Reviews, and Ovid/PsychINFO were searched for articles published from January 1, 2013, to June 30, 2019, to identify meta-analyses conducted in CHR-P individuals. MEDLINE was used to search the reference lists of retrieved articles. Data obtained from each article included first author, year of publication, topic investigated, type of publication, study design and number, sample size of CHR-P population and comparison group, type of comparison group, age and sex of CHR-P individuals, type of prognostic assessment, interventions, quality assessment (using AMSTAR [Assessing the Methodological Quality of Systematic Reviews]), and key findings with their effect sizes. Findings In total, 42 meta-analyses published in the past 6 years and encompassing 81 outcomes were included. For the detection component, CHR-P individuals were young (mean [SD] age, 20.6 [3.2] years), were more frequently male (58%), and predominantly presented with attenuated psychotic symptoms lasting for more than 1 year before their presentation at specialized services. CHR-P individuals accumulated several sociodemographic risk factors compared with control participants. Substance use (33% tobacco use and 27% cannabis use), comorbid mental disorders (41% with depressive disorders and 15% with anxiety disorders), suicidal ideation (66%), and self-harm (49%) were also frequently seen in CHR-P individuals. CHR-P individuals showed impairments in work (Cohend = 0.57) or educational functioning (Cohend = 0.21), social functioning (Cohend = 1.25), and quality of life (Cohend = 1.75). Several neurobiological and neurocognitive alterations were confirmed in this study. For the prognosis component, the prognostic accuracy of CHR-P instruments was good, provided they were used in clinical samples. Overall, risk of psychosis was 22% at 3 years, and the risk was the highest in the brief and limited intermittent psychotic symptoms subgroup (38%). Baseline severity of attenuated psychotic (Cohend = 0.35) and negative symptoms (Cohend = 0.39) as well as low functioning (Cohend = 0.29) were associated with an increased risk of psychosis. Controlling risk enrichment and implementing sequential risk assessments can optimize prognostic accuracy. For the intervention component, no robust evidence yet exists to favor any indicated intervention over another (including needs-based interventions and control conditions) for preventing psychosis or ameliorating any other outcome in CHR-P individuals. However, because the uncertainty of this evidence is high, needs-based and psychological interventions should still be offered. Conclusions and Relevance This review confirmed recent substantial advancements in the detection and prognosis of CHR-P individuals while suggesting that effective indicated interventions need to be identified. This evidence suggests a need for specialized services to detect CHR-P individuals in primary and secondary care settings, to formulate a prognosis with validated psychometric instruments, and to offer needs-based and psychological interventions.

Vascular permeability and drug delivery in cancers.

Abstract: The endothelial barrier strictly maintains vascular and tissue homeostasis, and therefore modulates many physiological processes such as angiogenesis, immune responses, and dynamic exchanges throughout organs. Consequently, alteration of this finely tuned function may have devastating consequences for the organism. This is particularly obvious in cancers, where a disorganized and leaky blood vessel network irrigates solid tumors. In this context, vascular permeability drives tumor-induced angiogenesis, blood flow disturbances, inflammatory cell infiltration, and tumor cell extravasation. This can directly restrain the efficacy of conventional therapies by limiting intravenous drug delivery. Indeed, for more effective anti-angiogenic therapies, it is now accepted that not only should excessive angiogenesis be alleviated, but also that the tumor vasculature needs to be normalized. Recovery of normal state vasculature requires diminishing hyperpermeability, increasing pericyte coverage, and restoring the basement membrane, to subsequently reduce hypoxia, and interstitial fluid pressure. In this review, we will introduce how vascular permeability accompanies tumor progression and, as a collateral damage, impacts on efficient drug delivery. The molecular mechanisms involved in tumor-driven vascular permeability will next be detailed, with a particular focus on the main factors produced by tumor cells, especially the emblematic vascular endothelial growth factor. Finally, new perspectives in cancer therapy will be presented, centered on the use of anti-permeability factors and normalization agents.