Understanding Intelligently Artificial Intelligence : a citizens' open formation

International audienceOur whole society is and will be deeply impacted by digital science and this takes a new qualitative and quantitative turn with what is named artificial intelligence (AI). We must allow everyone to master, thus understand how all this works. This means computational thinking discovery and machine learning initiation. Directly inspired by the Finnish initiative to train 1% of its population on these subjects and after our success in providing a hybrid formation on computational thinking for teachers and citizens not familiar with computer science where more 45000 persons have been reached, yielding a satisfaction level higher than 90%, we have built and now operate a citizen training in AI in the broad sense, intended to a large public beyond the school domain, with the goal of giving rise to an ubiquitary citizen university in digital science and cultur

Polychondrites atrophiantes révélées par une urticaire annulaire fixe

La polychondrite atrophiante (PCA) est une maladie auto-immune rare qui atteint les cartilages, à l'origine de poussées inflammatoires récidivantes et progressivement atrophiantes. Au cours de cette maladie, des manifestations cutanées sont fréquemment rapportées (35% des cas). Ces manifestations sont décrites comme multiples, polymorphes et non spécifiques. Nous rapportons une série de 11 patients atteints de PCA, qui à l'inverse avaient présenté des lésions cutanées frappantes du fait de leur similitude, à type de papules urticariennes fixes du tronc. PATIENTS ET METHODES : Nous avons réalisé une étude rétrospective des dossiers des patients suivis au cours d'une période allant de 1995 à 2002. Les critères d'inclusion étaient les suivants : 1) patients atteints de PCA ; 2) lésions urticariennes décrites au cours du suivi. Pour chaque patient, différents points étaient relevés : le sexe, l'âge, la description des lésions cutanées, les cartilages atteints par la PCA, le délai entre l'apparition de la PCA et de ces papules, les résultats de la numération formule sanguine, du volume globulaire moyen (VGM), du taux de l'hormone thyréostimuline (TSH) sanguin, de la créatininémie, des dosages des vitamines B12 et B9. Histologiquement, les résultats des biopsies cartilagineuses, du myélogramme et des biopsies cutanées étaient relevés, ces analyses n'étant pas systématiques. R ES U LTATS : Onze patients ont été inclus. Il s'agissait de 10 hommes et d'une femme. L'âge moyen était de 63.4 ans [30 -73]. Dans la majorité des cas (9/11 patients) les papules urticariennes avaient une forme annulaire, elles prédominaient nettement sur le tronc dans les 11 cas avec quelques éléments sur les membres dans 5 cas. Le visage était toujours épargné. L'analyse histologique des lésions urticariennes, retrouvait chez 9 d'entre eux un aspect de vascularite lymphocytaire. L'atteinte cartilagineuse concernait les oreilles dans tous les cas, elle était associée à une atteinte du nez dans 2 cas et du cartilage cricoïde dans 1 cas. Dans 10 cas les lésions cutanées étaient apparues avant l'atteinte cartilagineuse la précédant d'un délai moyen de 32 mois. Un syndrome myélodysplasique était histologiquement confirmé ou fortement suspecté pour 8 patients. DISCUSSION : Ces observations étaient intéressantes du fait de leur présentation clinique très particulière et toujours identique. Il s'agissait d'hommes d'âge moyen 63 ans, ayant eu des lésions cutanées avant l'apparition des chondrites, 8 (73%) d'entre eux étaient atteints d'une myélodysplasie habituellement décrite dans 10% des PCA dans la littérature. L'aspect histologique de ces papules était une vascularite lymphocytaire alors que l'aspect habituellement rapporté est une vascularite leucocytoclasique. L'évolution de ces patientes était rapidement défavorable pour au moins 3 d'entre eux. Conclusion : Nous pensons qu'il pourrait s'agir d'une forme particulière de PCA, révélée par des lésions cutanées spécifiques et au pronostic plus péjoratif.ROUEN-BU Médecine-Pharmacie (765402102) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Understanding Intelligently Artificial Intelligence : a citizens' open formation

International audienceOur whole society is and will be deeply impacted by digital science and this takes a new qualitative and quantitative turn with what is named artificial intelligence (AI). We must allow everyone to master, thus understand how all this works. This means computational thinking discovery and machine learning initiation. Directly inspired by the Finnish initiative to train 1% of its population on these subjects and after our success in providing a hybrid formation on computational thinking for teachers and citizens not familiar with computer science where more 45000 persons have been reached, yielding a satisfaction level higher than 90%, we have built and now operate a citizen training in AI in the broad sense, intended to a large public beyond the school domain, with the goal of giving rise to an ubiquitary citizen university in digital science and cultur

Late-onset adverse events of anti-PD1 therapy in melanoma patients: An observational study from MELBASE, a nationwide prospective cohort

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Non-V600E/K BRAF Mutations in Metastatic Melanoma: Molecular Description, Frequency, and Effectiveness of Targeted Therapy in a Large National Cohort

International audiencePurpose: Mitogen-activating protein kinase inhibitors (MAPKis) are largely used in V600E/K BRAF–mutated metastatic melanomas, but data regarding effectiveness of targeted therapy in patients with rare BRAF mutations and molecular description of these infrequent mutations are scarce. Patients and methods: A multicenter study was conducted on patients with metastatic melanoma harboring a well-identified mutation of BRAF and enrolled from March 2013 to June 2021 in the French nationwide prospective cohort MelBase. The molecular BRAF mutation pattern, response to MAPKis when applicable, and survival data were analyzed. Results: Of 856 selected patients, 51 (6%) harbored a non-V600E/K BRAF mutation involving codons V600 (24 of 51, 47%; V600G 27.4%, V600R 15.6%), K601 (6 of 51, 11.7%), and L597 (4 of 51, 7.8%). An objective response to MAPKis either BRAF inhibitor (BRAFi) alone or combined with MEK inhibitor was achieved in 56% (353 of 631) of V600E/K, 58% (11 of 19) of non-E/K V600, and 22% (2 of 9) of non-V600 BRAF-mutated patients, with a median progression-free survival of 7.7, 7.8, and 2.8 months, respectively. Overall, objective response rate was higher with BRAFi + MEK inhibitor combination than with BRAFi in monotherapy for each subset. Conclusion: Rare BRAF mutations are not anecdotal in the metastatic melanoma population. Although data interpretation must remain careful owing to the limited size of some subsets of patients, non-E/K V600 BRAF mutations seem to confer a high sensitivity to targeted therapy, whereas MAPKis seem less effective in patients with non-V600 BRAF mutations. However, this strategy may be used as an alternative option in the case of immunotherapy failure in the latter population

Combined Nivolumab and Ipilimumab in Octogenarian and Nonagenarian Melanoma Patients

International audienceData regarding elderly melanoma patients treated with anti-PD-1 or anti-CTLA-4 antibodies are in favor of tolerability outcomes that are similar to those of younger counterparts. However, there are very few studies focusing on elderly patients receiving nivolumab combined with ipilimumab (NIVO + IPI). Here, we ask what are the current prescribing patterns of NIVO + IPI in the very elderly population and analyze the tolerance profile. This French multicenter retrospective study was conducted on 60 melanoma patients aged 80 years and older treated with NIVO + IPI between January 2011 and June 2022. The mean age at first NIVO + IPI administration was 83.7 years (range: 79.3–93.3 years). Fifty-five patients (92%) were in good general condition and lived at home. Two dosing regimens were used: NIVO 1 mg/kg + IPI 3 mg/kg Q3W (NIVO1 + IPI3) in 27 patients (45%) and NIVO 3 mg/kg + IPI 1 mg/kg Q3W (NIVO3 + IPI1) in 33 patients (55%). NIVO + IPI was a first-line treatment in 39 patients (65%). The global prevalence of immune-related adverse events was 63% (38/60), with 27% (16/60) being of grade 3 or higher. Grade ≥ 3 adverse events were less frequent in patients treated with NIVO3 + IPI1 compared with those treated with NIVO1 + IPI3 (12% versus 44%, p = 0.04). In conclusion, the prescribing patterns of NIVO + IPI in very elderly patients are heterogeneous in terms of the dosing regimen and line of treatment. The safety profile of NIVO + IPI is reassuring; whether or not the low-dose regimen NIVO3 + IPI1 should be preferred over NIVO1 + IPI3 in patients aged 80 years or older remains an open question

Pembrolizumab as first line therapy in patients with unresectable squamous cell carcinoma of the skin: Interim results of the phase 2 CARSKIN trial.

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Tolerance and Effectiveness of Targeted Therapies in Aged Patients with Metastatic Melanoma

International audiencePurpose: Melanoma’s incidence is increasing, and elderly people could be significantly impacted since the majority occurs in people over 65 years of age. Combined BRAF and MEK targeted therapies (TT) are current standard regimen for BRAF mutated metastatic melanoma (MM). Except for subgroups of pivotal trials, little data are available for TT in this population. Materials and Methods: Outcomes were explored in real life patients from MelBase, a French multicentric biobank dedicated to the prospective follow-up of unresectable stage III or IV melanoma. Patients treated by BRAF TT and/or MEK TT combined or not, were included from 2013 to 2017 in 2 groups: group 1 ≤ 65-year-old (yo), group 2 > 65 yo, analyzed for tolerance and efficacy. Results: 353 patients were included: 231 in group 1, 122 in group 2. Median follow-up was 12 months (M). Median time of treatment was 6.9 M. A total of 80% had at least one Adverse Effect (AE). Most frequent AE (all grades) were mainly skin and subcutaneous, general, and gastrointestinal disorders. A total of 31% of AE were grade 3–4: 28% in group 1 and 39% in group 2 (p = 0.05). No differences were observed in all AE grades proportion, dose modifications, interruptions, and discontinuations. For each group, median overall survival was 20.3 M (CI 95%: 15.5–27.9) and 16.3 M (CI: 14.5–26.9), respectively (p = 0.8). Median progression free survival was 7.8 M (6.4–9.9) and 7.7 M (CI: 5.8–11.3) (p = 0.4). Objective response rate was 59% and 50% (p = 0.6). Conclusion: This study on a large multicentric cohort is the first to assess that TT is well tolerated in elderly BRAF-mutated patients such as in patients younger than 65. Efficacy was similar between groups with outcomes reaching those from pivotal studies. There is thus no argument against using TT in elderly people, although an onco-geriatric opinion is welcome for the most vulnerable