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IMRED, ICMJE/COPE, EQUATOR : cadres et normes de publication des recherches originales en santé publique
No full textNational audienceThis article presents a structured reflection on the standards and frameworks governing the publication of original research, focusing on the biomedical field, and more specifically, on public health. It draws on Le Moigne’s general systems theory and its systemic triangulation, which analyzes complex objects (in this case, the publication system) through three complementary poles: ontological (what it is), functional (what it does), and genetic (how it evolves). These three dimensions help illuminate the main normative frameworks of publication: (i) the IMRAD structure (Introduction, Methods, Results, and Discussion), which illustrates the ontological pole by ensuring the clarity and replicability of scientific results; (ii) the recommendations of the International Committee of Medical Journal Editors (ICMJE) and the Committee on Publication Ethics (COPE), which provide functional and ethical guidance for the writing and submission of articles, including the roles and responsibilities of authors and contributors; and (iii) the guidelines of the EQUATOR network (Enhancing the QUAlity and Transparency Of health Research), which influence both the writing of articles and the design of studies themselves (genetic pole).The analysis offers perspectives to incorporate Le Moigne’s teleological pole, which questions the very purpose of the scientific publication system and its alignment with major societal challenges. Together, these evolving frameworks interact and continuously develop to promote scientific publications that are not only clear and well-structured but also rigorous in both methodological and ethical terms, while opening space for reflection on the place and role of science in our societies.Cet article propose une réflexion structurée sur les normes et cadres qui régissent la publication de recherches originales, en se concentrant sur le domaine biomédical et plus particulièrement sur la santé publique. Il s’appuie sur la théorie du système général de Le Moigne et sa triangulation systémique, qui analyse les objets complexes (ici, le système de publication) à travers trois pôles complémentaires : ontologique (ce que c’est), fonctionnel (ce que cela fait) et génétique (comment cela évolue). Ces trois dimensions permettent d’éclairer les grands cadres normatifs de la publication : (i) la structure IMRED (Introduction, Méthodes, Résultats et Discussion), qui illustre le pôle ontologique en assurant la lisibilité et la réplicabilité des résultats scientifiques ; (ii) les recommandations du Comité international des éditeurs de revues médicales (ICMJE) et du Comité d’éthique de la publication (COPE), qui fournissent des repères fonctionnels et éthiques pour la rédaction et la soumission des articles, intégrant notamment les rôles et responsabilités des auteurs et contributeurs ; (iii) les lignes directrices du réseau EQUATOR (Enhancing the QUAlity and Transparency Of health Research), qui influencent à la fois la rédaction des articles et la conception même des recherches (pôle génétique).L’analyse énonce des perspectives afin d’intégrer le pôle téléologique de Le Moigne, qui interroge la finalité même du système de publication scientifique et sa cohérence avec les grands enjeux sociétaux. Ensemble, ces cadres évolutifs interagissent et évoluent constamment pour tendre vers des publications scientifiques non seulement claires et bien structurées, mais aussi rigoureuses sur les plans méthodologiques et éthiques, tout en ouvrant un espace de réflexion sur la place et le rôle de la science dans nos sociétés
Alterations in Respiratory Heart Rate Variability in Brain-Injured Neuro-ICU Patients Compared with Healthy Humans
No full textBackground: Respiratory heart rate variability (RespHRV), the physiological variation in heart rate in phase with breathing, is mainly generated by central brainstem mechanisms. Its characteristics and determinants in brain-injured patients in the neuro-intensive care unit (neuro-ICU) are poorly understood.Objective: To characterize RespHRV amplitude and phase in brain-injured patients compared to healthy participants, and to explore clinical variables influencing RespHRV in the neuro-ICU.Methods: We analyzed 55 brain-injured patients (traumatic brain injury, aneurysmal subarachnoid hemorrhage, or other causes) and 31 healthy controls. ECG and respiratory signals were recorded and processed to extract cycle-by-cycle RespHRV amplitude and phase. Group differences were assessed using Mann-Whitney and Watson-Williams tests. In an additional analysis, 55 patients' RespHRV amplitude and phase were modeled using generalized linear mixed-effects models to evaluate the impact of sedation, mechanical ventilation mode, vasoactive and analgesic drugs, and time, including random intercepts and slopes for subjects.Results: Compared to controls, brain-injured patients exhibited a significantly lower RespHRV amplitude (1.04 [0.45, 1.96] vs. 6.21 [4.08, 9.34] bpm; p < 0.001) and an inverted RespHRV phase, with peak heart rate occurring during expiration rather than inspiration. Mixed-effects modeling revealed that machine-triggered ventilation and high level of sedation induced a significant reduction in RespHRV amplitude. Conclusions: Brain-injured patients demonstrate markedly impaired central generation of RespHRV, with peripheral contributors likely accounting for the remaining variability. Ventilation mode and pharmacological interventions strongly alter RespHRV. Restoration of normal RespHRV patterns may serve as a physiological marker of autonomic and brainstem recovery, warranting further investigation in longitudinal studies.</div
[Poster]#794 Phenylacetylglutamine's role in the link between uremic toxins and cognition in chronic kidney disease: a CKD-REIN cohort study
No full textInternational audienceBackground and Aims Chronic kidney disease (CKD) leads to the accumulation of uremic toxins (UTs). Many studies have suggested that UTs are associated with cognitive impairment (CI) in CKD patients. It was recently reported that phenylacetylglutamine (PAG) contributes to the association between CKD and CI. To the best of our knowledge, this association has not been investigated in non-dialysis-dependent adults with CKD. Method The CKD-REIN cohort study included 3033 patients with CKD stages 2 to 5; the present cross-sectional analysis included those with a serum PAG measurement and a Mini-Mental State Examination (MMSE) score within 3 months of each other. CI was defined as an MMSE score ≤26/30. Logistic regression models were used to assess the association between the serum PAG levels and CI. Results Of the 2590 patients included (mean (standard deviation (SD)) age: 67 (13); males: 66%; mean (SD) estimated glomerular filtration rate (eGFR): 34 (13) mL/min/1.73 m2; median [interquartile range] serum PAG level: 2.1 [1.2–3.6] mg/L), 908 (35%) presented an MMSE score ≤26/30. After adjustment for sociodemographic factors (age, sex, and educational level), cardiovascular risk factors, cerebrovascular disease, eGFR, urinary albumin to creatinine ratio and other UTs known to be associated with CI risk (indoxyl sulfate, p-cresyl sulfate and trimethylamine-N-oxide), a two-fold increase in the serum PAG levels was associated with CI (odds ratio [95% confidence interval]: 1.15 [1.02, 1.29]). Conclusion The results of this large study show that elevated serum PAG levels are associated with CI in non-dialysis-dependent adults with CKD and highlight a new physiological pathway underlying this association between UTs and CI. Further studies are needed to confirm the causal nature of this association and to explore strategies for reducing serum PAG levels and thus protecting cognitive function
The impact of ABO compatibility on allogeneic hematopoietic cell transplantation outcomes: a contemporary and comprehensive study from the transplant complications working party of the EBMT.
No full textInternational audienceThe role of ABO blood group system mismatch on allogeneic hematopoietic cell transplantation (allo-HCT) outcomes is controversial since current publications of large datasets are lacking. We retrospectively analyzed 30,487 patients transplanted between 2010 and 2021 using the EBMT registry to assess ABO incompatibility's effect on non-relapse mortality (NRM), overall survival (OS), progression-free survival (PFS), relapse incidence (RI), acute GvHD (aGvHD), chronic GvHD (cGvHD), and neutrophil engraftment. Transplantations were classified as ABO-compatible (56.3%), major (18.1%), minor (20.1%), and bidirectional (5.5%) incompatibilities. Mainly peripheral blood stem cells (PBSC) were used as the cell source in 85.6% of cases. Multivariate analysis found no significant association between compatibility status, with the compatible group serving as the reference, and NRM, OS, PFS, RI or cGvHD. The incidence of non-engraftment was significantly higher in the major (HR 1.04, 95% CI 1.01-1.07, p = 0.021) and bidirectional (HR 1.09, 95% CI 1.03-1.15, p = 0.003) incompatibilities. At the same time, the risk of severe aGvHD grades III-IV was lower in the major incompatibility group (HR 0.85, 95% CI 0.77-0.94, p = 0.001). Our large contemporary study, showing no major impact on outcomes, suggests that the ABO blood group system should not be a primary consideration in donor selection for PBSC-based allo-HCT
Structural and functional characterization of the cardiac mitochondria-associated reticular membranes in the ob/ob mouse model
No full textInternational audienceType 2 diabetes (T2D) and obesity strongly lead to diabetic cardiomyopathy (DCM). The involvement of mitochondria-associated reticular membranes (MAMs), a signaling hub in the cardiomyocyte, starts to be demonstrated in T2D-related metabolic disorders. We recently discovered a cardiac MAM Ca2+ uncoupling in a high-fat high-sucrose diet (HFHSD)-induced mouse model of DCM. To better determine the role of MAMs in the progression of DCM, we here aimed to characterize the proteomic composition and function of the cardiac MAMs of another obesogenic T2D mouse model, the leptin-deficient ob/ob mouse. 12-week old male C57Bl6-N ob/ob mice displayed strain rate dysfunction and concentric remodeling, while no change was observed in fractional shortening or diastolic function. Increased lipid deposition but no fibrosis was measured in the ob/ob heart compared to WT. Electron microscopy analysis revealed that cardiac MAM length and width were similar between both groups. A trend towards an increased MAM protein content was measured in the ob/ob heart. MAM proteome analyses showed mainly increased processes in ob/ob hearts: cellular response to stress, lipid metabolism, ion transport and membrane organization. Functionally, MAM-driven Ca2+ fluxes were unchanged but hypoxic stress induced a cell death increase in the ob/ob cardiomyocyte. Mitochondrial respiration, cardiomyocyte shortening, ATP and ROS content were similar between groups. To conclude, at that age, while being strongly hyperglycemic and insulin-resistant, the ob/ob mouse model rather displays a modest DCM without strong changes in MAMs: preserved structural and functional MAM Ca2+ coupling but increased response to stress
The impact of primary decompressive craniectomy in ruptured middle cerebral artery aneurysms with intraparenchymal hematoma
No full textInternational audienceBackground: Ruptured middle cerebral artery aneurysm (MCAa) with intraparenchymal hematoma (IPH) can benefit at the same time from evacuation of the hematoma and exclusion of the aneurysm of a decompressive craniectomy (DC). To date, there are no clear recommendations for performing a DC in such cases.Methods: We retrospectively collected data from nine French neurosurgical units from January 1, 2013 to December 31, 2020. All MCAa patients with IPH requiring evacuation of the IPH were included in this study. Poor outcomes were defined by an mRs score of 3-6 at 6 months. Propensity score matching was used to analyze the potential effects of DC.Results: Between January 2013 and December 2020, 198 MCAa ruptured with IPH were treated, including 162 MCAa requiring evacuation of the IPH. 50 were treated with DC and 112 without DC. After matching 72 patients, poor neurological prognosis was observed in 27/36 patients (75%) in the DC group versus 18/36 (50%) in the non-DC group (p = 0.026).Conclusion: Primary decompressive craniectomy in patients with ruptured MCAa and IPH requiring surgical evacuation increases the risk of poor neurological outcome. RCT are needed to confirm this hypothesis
Les propriétés ultrastructurales du réticulum endoplasmique régissent la signalisation des microdomaines calciques dans les prolongements astrocytaires périsynaptiques.
No full textInternational audienceAstrocytes recently emerged as key regulators of information processing in the brain. Ca2+ signals in perisynaptic astrocytic processes (PAPs) notably allow astrocytes to fine-tune neurotransmission at tripartite synapses. As most PAPs are below the diffraction limit, their content in Ca2+ stores and the contribution of the latter to astrocytic Ca2+ activity is unclear. Here, we reconstruct hippocampal tripartite synapses in 3D from a high resolution electron microscopy (EM) dataset and find that 75% of PAPs contain some endoplasmic reticulum (ER), a major astrocytic Ca2+ store. The ER in PAPs displays strikingly diverse shapes and intracellular spatial distributions. To investigate the causal relationship between each of these geometrical properties and the spatio-temporal characteristics of Ca2+ signals, we implemented an algorithm that generates 3D PAP meshes by altering the distribution of the ER independently from ER and cell shape. Reaction-diffusion simulations in these meshes reveal that astrocyte activity is governed by a complex interplay between the location of Ca2+ channels, ER surface-volume ratio and spatial distribution. In particular, our results suggest that ER-PM contact sites can act as local signal amplifiers if equipped with IP3R clusters but attenuate PAP Ca2+ activity in the absence of clustering. This study sheds new light on the ultrastructural basis of the diverse astrocytic Ca2+ microdomain signals and on the mechanisms that regulate neuron-astrocyte signal transmission at tripartite synapses.Les astrocytes sont des cellules jouant un rôle clé dans la régulation du traitement de l'information dans le cerveau. Les signaux calciques dans les prolongements astrocytaires périsynaptiques (PAP) permettent notamment aux astrocytes de réguler la neurotransmission au niveau des synapses tripartites. Comme la plupart des PAPs sont en dessous de la limite de diffraction, leur contenu en réserves de calcium et la contribution de ces derniers à l'activité calcique astrocytaire sont méconnus. Ici, nous reconstruisons des synapses tripartites de l'hippocampe en 3D à partir de données de microscopie électronique (ME) à haute résolution et constatons que 75 % des PAPs contiennent du réticulum endoplasmique (RE), un important réservoir de calcium astrocytaire. Le RE dans les PAPs présente des formes et des distributions spatiales intracellulaires étonnamment diverses. Afin d'étudier la relation causale entre chacune de ces propriétés géométriques et les caractéristiques spatio-temporelles des signaux calciques, nous avons développé un algorithme qui génère des maillages de PAPs en 3D en modifiant la distribution du RE indépendamment de la forme du RE et de la cellule. Des simulations de réaction-diffusion dans ces maillages révèlent que l'activité des astrocytes est régie par une interaction complexe entre l'emplacement des canaux calciques, le rapport surface/volume, et la distribution spatiale du RE. En particulier, nos résultats suggèrent que les sites de contact entre le RE et la membrane plasmique peuvent agir comme des amplificateurs de signaux locaux s'ils sont équipés de clusters IP3R, mais atténuent l'activité calcique dans les PAPs en l'absence de clustering. Cette étude apporte un éclairage nouveau sur la base ultrastructurale des divers signaux des microdomaines calciques astrocytaires et sur les mécanismes qui régulent la transmission des signaux entre neurones et astrocytes au niveau des synapses tripartites
Diagnosis, management and treatment of the Alport syndrome – 2024 guideline on behalf of ERKNet, ERA and ESPN
No full textInternational audienceGlomerular nephropathy resulting from the genetic defects in COL4A3/4/5 genes including the classical Alport syndrome is the second most common hereditary kidney disease characterized by persistent haematuria progressing to the need for kidney replacement therapy, frequently associated with sensorineural deafness, and occasionally with ocular anomalies.Diagnosis and management of COL4A3/4/5 glomerulopathy is a great challenge due to its phenotypic heterogeneity, multiple modes of inheritance, variable expressivity, and disease penetrance of individual variants as well as imperfect prognostic and progression factors and scarce and limited clinical trials, especially in children.As a joint initiative of the European Rare Kidney disease reference Network (ERKNet), European Renal Association (ERA Genes&Kidney), and European Society for Paediatric Nephrology (ESPN) Inherited renal disorders working group, a team of experts including adult and paediatric nephrologists, kidney geneticists, audiologists, ophthalmologists, and a kidney pathologist were</div
Deep phenotyping of nodal T-cell lymphomas reveals immune alterations and therapeutic targets
No full textInternational audienceWhereas immunotherapies have revolutionized the treatment of different solid and hematological cancers, their efficacy in nodal peripheral T-cell lymphomas (PTCLs) is limited, due to a lack of understanding of the immune response they trigger. To fully characterize the immune tumor microenvironment (TME) of PTCLs, we performed spectral flow cytometry analyses on 11 angioimmunoblastic T-cell lymphomas (AITL), 7 PTCL, not otherwise specified (PTCL, NOS) lymph node samples, and 10 non-tumoral control samples. The PTCL TME contained a larger proportion of regulatory T cells and exhausted CD8+ T cells, with enriched expression of druggable immune checkpoints. Interestingly, CD39 expression was up-regulated at the surface of most immune cells, and a multi-immunofluorescence analyses on a retrospective cohort of 43 AITL patients demonstrated a significant association between high CD39 expression by T cells and poor patient prognosis. Together, our study unravels the complex TME of nodal PTCLs, identifies targetable immune checkpoints, and highlights CD39 as a novel prognostic factor