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In patients with suspected or known coronary artery disease, traditional prognostic risk assessment is based on a limited selection of clinical and imaging findings. Machine learning (ML) methods can take into account a greater number and complexity of variables.This study sought to investigate the feasibility and accuracy of ML using stress cardiac magnetic resonance (CMR) and clinical data to predict 10-year all-cause mortality in patients with suspected or known coronary artery disease, and compared its performance with existing clinical or CMR scores.Between 2008 and 2018, a retrospective cohort study with a median follow-up of 6.0 (IQR: 5.0-8.0) years included all consecutive patients referred for stress CMR. Twenty-three clinical and 11 stress CMR parameters were evaluated. ML involved automated feature selection by random survival forest, model building with a multiple fractional polynomial algorithm, and 5 repetitions of 10-fold stratified cross-validation. The primary outcome was all-cause death based on the electronic National Death Registry. The external validation cohort of the ML score was performed in another center.Of 31,752 consecutive patients (mean age: 63.7 ± 12.1 years, and 65.7% male), 2,679 (8.4%) died with 206,453 patient-years of follow-up. The ML score (ranging from 0 to 10 points) exhibited a higher area under the curve compared with Clinical and Stress Cardiac Magnetic Resonance score, European Systematic Coronary Risk Estimation score, QRISK3 score, Framingham Risk Score, and stress CMR data alone for prediction of 10-year all-cause mortality (ML score: 0.76 vs Clinical and Stress Cardiac Magnetic Resonance score: 0.68, European Systematic Coronary Risk Estimation score: 0.66, QRISK3 score: 0.64, Framingham Risk Score: 0.63, extent of inducible ischemia: 0.66, extent of late gadolinium enhancement: 0.65; all P 0.001). The ML score also exhibited a good area under the curve in the external cohort (0.75).The ML score including clinical and stress CMR data exhibited a higher prognostic value to predict 10-year death compared with all traditional clinical or CMR scores.

Summary Although type 1 diabetes is traditionally considered a disease of lean people, overweight and obesity are becoming increasingly more common in individuals with type 1 diabetes. Non-physiological insulin replacement that causes peripheral hyperinsulinaemia, insulin profiles that do not match basal and mealtime insulin needs, defensive snacking to avoid hypoglycaemia, or a combination of these, are believed to affect body composition and drive excessive accumulation of body fat in people with type 1 diabetes. The consequences of overweight or obesity in people with type 1 diabetes are of particular concern, as they increase the risk of both diabetes-related and obesity-related complications, including cardiovascular disease, stroke, and various types of cancer. In this Review, we summarise the current understanding of the aetiology and consequences of excessive bodyweight in people with type 1 diabetes and highlight the need to optimise future prevention and treatment strategies in this population.

Resume L’hyperplasie congenitale des surrenales est une pathologie liee a une mutation genetique responsable d’une production exageree de testosterone des la vie in utero. Nous rapportons le cas d’une patiente de 15 ans atteinte de la maladie, particulierement inobservante de son traitement de substitution hormonale, chez laquelle une « prostate » a ete mise en evidence lors d’une IRM realisee pour un bilan de douleurs pelviennes chroniques et de troubles urinaires.

International audience; Objectives: To evaluate the applicability and compliance with guidelines for early initiation of long-term prophylaxis in infants with severe hemophilia A and to identify factors associated with guideline compliance.Study design: This real-world, prospective, multicenter, population-based FranceCoag study included almost all French boys with severe hemophilia A, born between 2000 and 2009 (ie, after guideline implementation).Results: We included 333 boys in the study cohort. The cumulative incidence of long-term prophylaxis use was 61.2% at 3 years of age vs 9.5% in a historical cohort of 39 boys born in 1996 (ie, before guideline implementation). The guidelines were not applicable in 23.1% of patients due to an early intracranial bleeding or inhibitor development. Long-term prophylaxis was delayed in 10.8% of patients. In the multivariate analysis, 2 variables were significantly associated with "timely long-term prophylaxis" as compared with "delayed long-term prophylaxis": hemophilia treating center location in the southern regions of France (OR 23.6, 95% CI 1.9-286.7, P = .013 vs Paris area) and older age at long-term prophylaxis indication (OR 7.2 for each additional year, 95% CI 1.2-43.2, P = .031). Long-term prophylaxis anticipation was observed in 39.0% of patients. Earlier birth year (OR 0.5, 95% CI 0.3-0.8, P = .010 for birth years 2005-2009 vs 2000-2004) and age at first factor replacement (OR 1.9 for each additional year, 95% CI 1.2-3.0, P = .005) were significantly associated with "long-term prophylaxis guideline compliance" vs "long-term prophylaxis anticipation."Conclusions: This study suggests that long-term prophylaxis guidelines are associated with increased long-term prophylaxis use. However, early initiation of long-term prophylaxis remains a challenge.

Resume L’hamartome kystique retrorectal ou « tailgut cyst » est une entite rare, dont l’aspect caracteristique en IRM merite d’etre connu par tout radiologue specialise en imagerie pelvienne. Sa semeiologie, relativement proche de celle des lesions d’endometriose profonde, peut aisement mener a une erreur diagnostique pour un œil non averti. Il existe un rare risque de degenerescence carcinomateuse, justifiant, selon les centres, une exerese chirurgicale prophylactique. Nous rapportons le cas d’une patiente suivie dans le cadre d’une endometriose. Une IRM precedente avait revele des atteintes d’endometriose profonde typiques, associees a des lesions plus « atypiques ».

Undoubtedly, the field of social sciences research in general and sociological research is particularly hard hit by the vicissitudes experienced by the theoretical discourse in the field of investigation of the sciences of man and society and its corollary, the practical discourse. This great influence has profoundly shaped the direction of sociological research from classical doctrines to empirical propositions developed by contemporary sociologists. Our paper attempts to analyze the relationship between the theoretical choice of academic social science research and practical content held within academic institutions. In other words the proposed paper proposes to examine the impact of theoretical languages and practices on methodological orientations compared with deferent languages of sociological research in Algeria since the first studies.

Tolerogenic dendritic cells (tDC) constitute a promising therapy for autoimmune diseases, since they can anergize T lymphocytes recognizing self-antigens. Patients with type 1 diabetes mellitus (T1D) have autoreactive T cells against pancreatic islet antigens (insulin, glutamic acid decarboxylase 65 -GAD65-). We aimed to determine the ability of tDC derived from T1D patients to inactivate their insulin- and GAD65-reactive T cells. CD14+ monocytes and CD4+CD45RA- effector/memory lymphocytes were isolated from 25 patients. Monocyte-derived DC were generated in the absence (control, cDC) or presence of IL-10 and TGF-β1 (tDC), and loaded with insulin or GAD65. DC were cultured with T lymphocytes (primary culture), and cell proliferation and cytokine secretion were determined. These lymphocytes were rechallenged with insulin-, GAD65- or candidin-pulsed cDC (secondary culture) to assess whether tDC rendered T cells hyporesponsive to further stimulation. In the primary cultures, tDC induced significant lower lymphocyte proliferation and IL-2 and IFN-γ secretion than cDC; in contrast, tDC induced higher IL-10 production. Lymphocytes from 60% of patients proliferated specifically against insulin or GAD65 (group 1), whereas 40% did not (group 2). Most patients from group 1 had controlled glycemia. The secondary cultures showed tolerance induction to insulin or GAD65 in 14 and 10 patients, respectively. A high percentage of these patients (70-80%) belonged to group 1. Importantly, tDC induced antigen-specific T-cell hyporesponsiveness, since the responses against unrelated antigens were unaffected. These results suggest that tDC therapy against multiple antigens might be useful in a subset of T1D patients.

Background: Hemarthroses in severe hemophilia precipitate physical, psychosocial and financial difficulties. Objective: To compare the effects of secondary prophylaxis with on-demand sucrose-formulated recombinant factor VIII (rFVIII-FS) therapy in severe hemophilia A. Patients and methods: This open-label study included patients aged 30– 45 years with factor VIII (FVIII) coagulant activity < 1 IU dL)1 who were using on-demand FVIII treatment. Patients were treated with rFVIII-FS on demand for 6 months, followed by 7 months prophylaxis (20–40 IU kg)1, three times perweek, with the first month considered a run-in). The primary endpoint was the number of hemarthroses. Results: Twenty patients were enrolled (n = 19 completed); the mean age was 36.4 years, and 16 had target joints. The median (25–75%) number of joint bleeds decreased significantly with prophylaxis [0 (0–3)] vs. on-demand [15 (11–26); P < 0.001] therapy. The number of all bleeds was 0 (0–3) vs. 20.5 (14–37; P < 0.001), respectively. Median (range) total Gilbert scores improved after prophylaxis [18 (3–39)] compared with on-demand [25 (4–46)] therapy, predominantly reflecting the improved bleeding score. Median time from last prophylactic infusion to bleed was 2 days; 82.5% of bleeds occurred 2–3 days after the last infusion. Median 48-h and 72-h FVIII trough levels measured during months 10 and 13 were consistently > 6 and > 4 IU dL)1, respectively. Treatment was well tolerated, and no inhibitor formation was observed. Conclusion: Secondary prophylaxis with rFVIII-FS significantly reduced the frequency of hemarthroses compared with on-demand therapy in adult patients with severe hemophilia A.

We report the case of a 50 year-old man factor VIII deficient haemophiliac and hepatitis C cirrhosis. The patient underwent orthotopic liver transplantation because of episodes of variceal bleeding and encephalopathy. He received factor VIII replacement therapy perioperatively. Factor VIII returned to normal within 24 hours postoperatively and factor VIII replacement was stopped. Liver transplantation can be considered as definitive therapy for haemophilia.

Resume Dans quatre etablissements de soins, des enquetes d'evaluation des pratiques de medecine transfusionnelle ont ete realisees a partir de questionnaires aupres du personnel infirmier. Le questionnaire utilise, rempli de facon anonyme, portait sur l'ensemble des connaissances et pratiques transfusionnelles et plus particulierement sur la pratique de la verification ultime dans l'une d'elles. Ces enquetes ont permis de relever des failles au niveau de l'etiquetage des tubes destines aux examens immuno-hematologiques, de la conservation des produits sanguins labiles dans les unites de soins et de la pratique de la verification ultime qui n'est pas toujours integralement realisee au lit du patient. Ces resultats ont permis de cibler les actions de formation a entreprendre dans le cadre de l'amelioration de la qualite de l'acte transfusionnel dans les etablissements de soins en conformite avec les obligations reglementaires.

In vitro differentiation of human monocytes (Mo) provides large amounts of mature and functionally competent macrophages (M phi) which may be used as potentially powerful anticancer agents for adoptive immunotherapy. Granulocyte macrophage-colony stimulating factor (GM-CSF) was evaluated for its ability to influence long term cultures of Mo-derived M phi. Large quantities of Mo isolated by leukapheresis and elutriation were cultured in non-adherent cell culture bags or in plastic flasks with or without GM-CSF. At various stages of differentiation, GM-CSF treated M phi were recovered and assayed for survival, morphology, surface antigens, functional properties and proliferation in comparison with control M phi. In the present paper, we demonstrate that GM-CSF at a concentration of 50 U/ml (5 ng/ml) promotes better cell survival and the differentiation of Mo into M phi displaying certain morphological differences as compared to control M phi such as an increased expression of Max-1 antigen, CR3 and Fc gamma II receptors, higher phagocytic properties and increased capacities of cytotoxicity and TNF secretion when the cells are further activated by IFN-gamma. Furthermore, GM-CSF treated cells exhibit a low-grade proliferation although the nature of the proliferating cells has not been entirely elucidated. We conclude that the GM-CSF treated M phi would be particularly suitable for adoptive immunotherapy.

In the present study, two strains of mice were used: the control C57 Black/6 and the experimental ZRDCT/An, composed of anophthalmic (AN), monocular (mono) and binocular (bi) animals. The circadian rest-activity rhythms of these mice, submitted to a 12 h/12 h light/dark (L/D) cycle, present different characteristics. In C57 Black/6 animals the rhythms are classically synchronized to the L/D cycle with a maximal activity during the dark period, mainly at its beginning. In the AN mice, without exception, the rhythms are free running. In the bi and mono animals they are either synchronized to the L/D cycle, or synchronized but phase shifted in comparison with C57 Black/6, or free running. For the mono and bi animals, the typical or atypical mode of synchronization of their rhythms to the L/D cycle appears to be correlated with the ganglion cell density. It is well known that such a retinal component ensures the retino-hypothalamic connections. In the C57 Black/6 and AN mice, differential pulse voltammetric measurements of 5-hydroxyindoleacetic acid (5-HIAA, peak 3) extracellular concentrations have been also realized together with polygraphic recordings of the sleep/waking cycle. In both strains, the height of the 5-HIAA peak 3 recorded in the cortex is always the highest during active waking, and decreases during slow wave sleep and paradoxical sleep. Further, a circadian variation of this signal is superimposed to that of the waking state amount. Such circadian variations are synchronized to the L/D cycle in C57 Black/6 animals and free running in the AN mice.

Le Reseau FranceCoag (RFC) est une cohorte de patients porteurs d’un deficit hereditaire en proteines coagulantes, dont la maladie de Willebrand (MW), mise en place en 2003. Les criteres d’inclusion pour la MW sont VWF:Ag