Audit about Medical Decision: Data Transmission Concerning Patients with Dementia Entering French Nursing Homes Does Not Confirm the Diagnosis

Background. Dementia was affecting 855.000 patients in France in 2007. Lanmeur's rural hospital population was representative of the French nursing home's population. The followup was assumed by local GPs, which is also usual care in France for nursing homes. The study looked at clinical and paraclinical data transmitted at the institutionalization time of patients suffering from dementia. Aim. showing that admission letters did allow establishing a diagnosis of dementia for the GPs. Method. we included all patients with dementia at the time of institutionalization between July 2000 and July 2007. We searched in the admission letters for 25 criteria extracted from the French guidelines for dementia and Alzheimer disease diagnosis (multiple cross-sectional analysis per year). Results. 293 patients were included. The median number of diagnostic criteria present in the letters of admission is 1 (first quartile: zero, third quartile: 4, and maximum: 12). Conclusions. the data in admission letters did not allow the diagnosis of dementia according to the French guidelines. We know that dementia is underchecked and undertreated in France according to the same guidelines. What consequences did this lack of basic data give on motivation for treatment and recurrent diagnosis process for GPs? This has to be evaluated

Selective pharmacologic targeting of CTPS1 shows single-agent activity and synergizes with BCL2 inhibition in aggressive mantle cell lymphoma

Innovative therapeutic strategies have emerged over the past decade to improve outcomes for most lymphoma patients. Nevertheless, the aggressive presentation seen in high-risk mantle cell lymphoma (MCL) patients remains an unmet medical need. The highly proliferative cells that characterize these tumors depend on nucleotide synthesis to ensure high DNA replication and RNA synthesis. To take advantage of this vulnerability, STP-B, a clinically available small molecule selectively targeting CTP synthase 1 (CTPS1) has been recently developed. CTPS1 is a key enzyme of the pyrimidine synthesis pathway mediated through its unique ability to provide enough CTP in highly proliferating cells. Herein, we demonstrated that CTPS1 was expressed in all MCL cells, and that its high expression was associated with unfavorable outcomes for patients treated with chemotherapy. Using aggressive MCL models characterized by blastoid morphology, TP53 mutation or polyresistance to targeted therapies, we showed that STP-B was highly effective at nanomolar concentrations in vitro and in vivo, irrespective of these high-risk features. Inhibition of CTPS1 rapidly leads to cell cycle arrest in early S-phase accompanied by inhibition of translation, including of the anti-apoptotic protein MCL1. Consequently, CTPS1 inhibition induced synergistic cell death in combination with the selective BCL2 inhibitor venetoclax, both in vitro and in vivo. Overall, our study identified CTPS1 as a promising target for MCL patients and provided a mechanism-based combination with the BCL2 inhibitor venetoclax for the design of future chemotherapy-free treatment regimens to overcome resistance

Instituer l’autonomie de vie. Une mise en perspective du livret contributif « L’autonomie de vie comme droit humain »

La démarche Capdroits a été initiée à la suite de l’interpellation suscitée par la Convention relative aux Droits des Personnes Handicapées (CDPH de l’ONU) et les controverses qu’elle a engagées. Elle a pour objet de recherche les droits humains et le handicap. Elle est basée sur la participation des personnes directement concernées par les situations de handicap à la démarche de recherche. Elle donne une importance particulière à leurs expertises d’usage et expérientielles, en mettant en œuvre une méthode de « mise en problème public de l’expérience ». Entre 2019 et 2022, nous nous sommes engagés dans une phase de recherche qui porte sur les conditions d’appropriation de l’article 19 de la CDPH et de son Observation générale n° 5 qui invite à développer des « stratégies et plan de désinstitutionnalisation ». Nous avons inscrit cette question de la « désinstitutionnalisation » et des institutions dans une réflexion plus générale sur l’autonomie de vie et avons formulé une prise de position sur la “désinstitutionnalisation” que nous proposons de mettre en perspective et d’approfondir dans cet article

Interest of a hotline for palliative care in Isere

International audienc

Interest of a hotline for palliative care in Isere

International audienc

Unraveling MCL biology to understand resistance and identify vulnerabilities

International audienceMantle cell lymphoma (MCL) is a rare (5-7%), aggressive B-cell non-Hodgkin's lymphoma with well-defined hallmarks (e.g. Cyclin D1, SOX11), and whose expansion is highly dependent on the tumor microenvironment (TME). Parallel drastic progresses in the understanding of the lymphomagenesis and improved treatments led to paradigm shift in this B-cell malignancy with now prolonged disease-free survival after intensive chemotherapy and anti-CD20 based maintenance. However, this toxic strategy is not applicable in frail or elderly patients and a small but significant part of the cases will present a refractory disease representing unmet medical needs. Importantly, the field has recently seen the rapid emergence of targeted and immune-based strategies with effective combinations relying on biological rationales to overcome malignant plasticity and intratumor heterogeneity. In this review, we expose how unraveling the biology of MCL allows to better understand the therapeutic resistances and to identify neo-vulnerabilities of tumors, which are essential to offer efficient novel strategies for high-risk patients. We first highlight the tumor intrinsic resistance mechanisms, and associated Achilles heels within various pathways such as NFkB, mitochondrial apoptosis, DNA repair or epigenetic regulators. We then place the tumor in its complex ecosystem to decipher the dialog with the multiple TME components and show how the resulting protumoral signals could be disrupted with innovative therapeutics strategies. Finally, we discuss how these progresses could be integrated in a personalized approach in MCL

Using Explanations to guide Adaptation

We present the adaptation process in a CBR application for decision support in the domain of industrial supervision. Our approach uses explanations to approximate relations between a problem description and its solution, and the adaptation process is guided by these explanations (a more detailed presentation has been done in [4]). 1 CBR and adaptation In problem solving, CBR avoids complex inferences by reusing past problem solving episodes. We hope that if the current problem is similar to a previous one, then the solution of the past problem should be reusable for the current problem with a low adaptation cost. As target and source generally always have some differences, the objective of the adaptation process is tending to focalize on these differences and to reflect them on the solution of the new problem. An adaptation process is necessary when the current problem is not strictly identical to a past one. The adaptation process is difficult to define and is the key step of the CBR..