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Circulating Stress Hormones, Brain Health, and Cognition in Healthy Older Adults: Cross-Sectional Findings and Sex Differences in Age-Well
No full textMedit-Ageing Research Group: Claire André, Pierre Champetier, Léa Chauveau, Fabienne Collette, Sophie Dautricourt , Robin de Flores, Vincent De La Sayette, Harriet Demnitz-King, Séverine Fauvel, Francesca Felisatti, Victor Ferment, Eglantine Ferrand-Devouge, Julie Gonneaud, Antoine Garnier-Crussard, Anaïs Hamel, Sacha Haudry, Pierre Krolak-Salmon, Elizabeth Kuhn, Valérie Lefranc, Antoine Lutz, Valentin Ourry, Cassandre Palix, Anne Quillard, Géraldine Rauchs, Eric Salmon, Edelweiss Touron, Patrik Vuilleumier, Tim Whitfield.International audienceBackgroundIncreased stress is a proposed risk factor for Alzheimer’s disease (AD). We examined cross-sectional associations between circulating stress biomarkers and multimodal measures of brain health and cognition susceptible to AD in older adults and sex-specific subgroups.MethodsBaseline data from 132 cognitively unimpaired participants without depression (age, mean ± SD = 74.0 ± 4.0 years, women: n = 80) in the Age-Well trial (NCT02977819) were included. Stress hormone levels were measured in overnight fasting blood serum (cortisol, dehydroepiandrosterone sulfate) and blood plasma (epinephrine, norepinephrine) samples. AD-sensitive measures of brain health, including glucose metabolism (n = 89), cerebral perfusion, gray matter volume, amyloid deposition in a priori regions of interest, and cognitive markers were evaluated. Models were adjusted for age, sex, education, trait anxiety, and depressive symptoms.ResultsHigher epinephrine levels were associated (false discovery rate–corrected p < .05) with lower glucose metabolism in the anterior cingulate cortex (β = −0.26, p = .008), posterior cingulate cortex (β = −0.32, p = .006), and precuneus (β = −0.27, p = .021) and lower perfusion in the posterior cingulate cortex (β = −0.23, p = .013). Interactions between stress hormones and sex showed (false discovery rate–corrected p < .05) that in women only, higher epinephrine was associated with larger anterior cingulate cortex volume (interaction: β = 0.32, p = .016), whereas in men only, higher cortisol was associated with lower episodic memory performance (interaction: β = 0.98, p = .012).ConclusionsThe current study demonstrates the involvement of circulating stress hormones, particularly epinephrine and cortisol, in greater resilience or vulnerability of brain health and cognitive indicators of susceptibility to AD in older adults. The identification of sex-specific patterns in these associations may inform the development of more effective and tailored interventions
CAR T-cell therapy in autoimmune diseases: where are we and where are we going?
No full textInternational audienceChimeric antigen receptor (CAR)-based therapies developed for the treatment of haematological malignancies have recently been repurposed to treat refractory systemic autoimmune diseases. In this Review we critically discuss the current data available on the use of CAR-based therapy in systemic autoimmune diseases, the current challenges, and the potential next steps toward their implementation into clinical practice. Beyond the targeting of B cells via CD19, we discuss the advantages and potential pitfalls of targeting plasma cells (B-cell Maturation Antigen or CD138) and other non-immune targets, such as fibroblast activated protein, and of aiming to restore immune homeostasis using CAR T regulatory cells. Crucial points need to be addressed for CAR-based therapy to become a viable treatment option for patients with systemic autoimmune diseases
Self-reported health effects after one year from a viper bite: A prospective study from France
No full textInternational audienceIn France, the summer period (from mid-April to mid-September) is particularly prone to viper envenomations by the two most common species, Vipera aspis and Vipera berus, which represents a significant public health issue. Although mortality is extremely low and systemic signs are rare, some patients experience long-term functional sequelae, highlighting the need for further exploration of the prolonged effects of snakebites. We conducted an observational study of viper bite cases in France collected during routine follow-ups by four Poison Control Centers. Patients were followed up by toxicologists using a standardized survey to assess recovery time and health indicators. Over two years, 170 patients were included, with a sex ratio of 1.54 (103 males vs. 67 females) and a median age of 46.2 years. The median recovery time was 21 days, with 84 % of patients healed by 6 months, and recovery probabilities of 0.47, 0.65, and 0.86 at 14, 30, and 180 days, respectively. Parameters associated with delayed recovery were severe bite, lower limb bite, female gender, inappropriate treatment, and time to hospital admission. Age and time to administration of antivenom had no effect. One month after the bite, 12.8 % of patients avoided the activity during which they were bitten, 5.6 % frequently thought about the bite, and 22.3 % were afraid of snakes; these figures increased to 14.6 %, 4.5 %, and 38.2 %, respectively, after one year. Other factors than severity of envenomation should be taken into account in the long-term prognostic assessment of patients. Psychological impacts, though not clinically classified as traumatic events, suggest a need to consider mental health in recovery. Prompt administration of antivenom and compliance with recommended management remain key elements of effective care. It is important to re-evaluate the need for patient follow-up in the light of the factors identified as affecting the early favourable evolution of symptoms
High-Dose Vitamin D in Clinically Isolated Syndrome Typical of Multiple Sclerosis The D-Lay MS Randomized Clinical Trial
No full textInternational audienceImportance Vitamin D deficiency is a risk factor for multiple sclerosis (MS) and is associated with the risk of disease activity, but data on the benefits of supplementation are conflicting. Objective To evaluate the efficacy of high-dose cholecalciferol as monotherapy in reducing disease activity in patients with clinically isolated syndrome (CIS) typical for MS. Design, Setting, and Participants The D-Lay MS trial was a parallel, double-blind, randomized placebo-controlled clinical trial in 36 MS centers in France. Patients were enrolled from July 2013 to December 2020 (final follow-up on January 18, 2023). Untreated patients with CIS aged 18 to 55 years with CIS duration less than 90 days, serum vitamin D concentration less than 100 nmol/L, and diagnostic magnetic resonance imaging (MRI) meeting 2010 criteria for dissemination in space or 2 or more lesions and presence of oligoclonal bands were recruited. Intervention Patients were randomized 1:1 to receive oral cholecalciferol 100 000 IU (n = 163) or placebo (n = 153) every 2 weeks for 24 months. Main Outcomes and Measures The primary outcome measure was disease activity, defined as occurrence of a relapse and/or MRI activity (new and/or contrast-enhancing lesions) over 24 months of follow-up, also analyzed as separate secondary outcomes. Results Of the 316 participants enrolled and randomized (median [IQR] age, 34 [28-42] years; 70% women), the primary analysis included 303 patients (95.9%) who took at least 1 dose of the study drug and 288 (91.1%) ultimately completed the 24-month trial. Disease activity was observed in 94 patients (60.3%) in the vitamin D group and 109 patients (74.1%) in the placebo group (hazard ratio [HR], 0.66 [95% CI, 0.50-0.87]; P = .004), and median time to disease activity was longer in the vitamin D group (432 vs 224 days; log-rank P = .003). All 3 secondary MRI outcomes reported significant differences favoring the vitamin D group vs the placebo group: MRI activity (89 patients [57.1%] vs 96 patients [65.3%]; HR, 0.71 [95% CI, 0.53-0.95]; P = .02), new lesions (72 patients [46.2%] vs 87 patients [59.2%]; HR, 0.61 [95% CI, 0.44-0.84]; P = .003), and contrast-enhancing lesions (29 patients [18.6%] vs 50 patients [34.0%]; HR, 0.47 [95% CI, 0.30-0.75]; P = .001). All 10 secondary clinical outcomes showed no significant difference, including relapse, which occurred in 28 patients (17.9%) in the vitamin D group vs 32 (21.8%) in the placebo group (HR, 0.69 [95% CI, 0.42-1.16]; P = .16). Results were similar in a subset of 247 patients meeting updated 2017 diagnostic criteria for relapsing-remitting MS at treatment initiation. Severe adverse events occurred in 17 patients in the vitamin D group and 13 in the placebo group, none of which were related to cholecalciferol. Conclusions and Relevance Oral cholecalciferol 100 000 IU every 2 weeks significantly reduced disease activity in CIS and early relapsing-remitting MS. These results warrant further investigation, including the potential role of pulse high-dose vitamin D as add-on therapy. Trial Registration ClinicalTrials.gov Identifier: NCT0181716
AI in Learning Anatomy and Restoring Central Incisors: A Comparative Study
No full textInternational audienceMore than 1 billion individuals worldwide have experienced dental trauma, particularly children aged 7 to 12 y, predominantly affecting the anterior teeth, which has a significant impact on oral health and esthetics. Rapid emergency restorations using composite resin are followed by medium-term lab-fabricated mock-ups. Recent advancements in artificial intelligence (AI) assist dental restorations, and the objective of this study was to compare the performances of different AI approaches for the learning and reconstruction of central incisors. The study was approved by ethical committees and followed AI in dentistry recommendations. STL files of mature permanent maxillary incisors without severe wear were collected from 3 universities. Principal component analysis (PCA) and Deep Learning of Signed Distance Functions (DeepSDF) models were trained using these files. The learning of PCA and DeepSDF approaches were 3-fold cross-validated, and their performances were assessed using the following metrics to measure the reconstruction accuracy: the difference of surfaces, volumes, lengths, average Euclidian distance, Hausdorff distance, and crown–root angulations. Explainability was assessed using feature contribution analysis for PCA and Stochastic Neighbor Embedding (t-SNE) for DeepSDF. DeepSDF showed significantly better precision in surface, volume, and Hausdorff distance metrics compared with PCA. For reconstructions, the lower size of the latent code of the DeepSDF model demonstrated lower performances compared with higher sizes. In addition, DeepSDF raised concerns about explainability. This study demonstrates the potential of PCA and DeepSDF approaches, particularly DeepSDF, for the learning and reconstruction of the anatomy of upper central incisors. To foster trust and acceptance, future research should, however, focus on improving the explainability of DeepSDF models and considering a broader range of factors that influence smile design. These high performances suggest potential clinical applications, such as assisting practitioners in future smile designs and oral rehabilitation using AI approaches
Endovascular Preparation With Innovative Custom-Made Stent-Graft Before Kidney Transplantation: The Solution for Patients With Hostile Iliac Calcification
No full textInternational audienceThe increasing age of patients with end-stage renal disease raises the issue of hostile arterial access for transplantation, with technical difficulties associated with clamping and suturing the iliac artery. Some of these patients -who theoretically represent those who would benefit the most from transplantation in terms of mortality -are contraindicated because of anatomical and medical issues. In this context, a specific endovascular device called EndoPreKiT (Endovascular Preparation for Kidney Transplantation) has been designed, enabling arterial access for transplantation via a mini-invasive procedure. It consists of a woven Dacron supported by self-expanding nitinol rings, ensuring anchorage and allowing arterial clamping. The middle part of the anterior face of the device is stentless, enabling the anastomosis directly onto the Dacron once the calcified artery wall has been removed. After a cadaveric study validating its technical feasibility, such device was successfully implanted in 10 patients considered unfit for transplantation due to severe wall calcification. Two of them have been successfully transplanted with excellent outcomes after 13 and 3 months of follow-up. EndoPreKiT device may be a significant breakthrough in transplant surgery, that could expand the horizon of eligibility to include even the most fragile patients with challenging arterial access
Is the brainstem involved in Robin Sequence? Results of heart rate analysis Dysrobin
No full textInternational audienc
Syndrome d’apnée obstructive du sommeil résiduel chez l'enfant ; Quand y penser ? Quels facteurs de risque ?
No full textInternational audienc
Usefulness of Cerebrospinal Fluid Alzheimer's disease biomarkers in older patients: Evidence from a national multicenter prospective study
No full textInternational audienceThe use of cerebrospinal (CSF) biomarkers in the diagnosis of Alzheimer's disease (AD) has been gaining interest in clinical practice. Although their usefulness has been demonstrated, their potential value in older patients remains debated. To assess whether knowledge of the results of CSF AD biomarkers was associated with the same gain in diagnostic confidence in older adults > 80 than in younger patients. Prospective multicenter study, including memory clinics physicians who completed a two-part questionnaire for all their patients addressing the requirement for assessment of Alzheimer's disease biomarkers in CSF proposed as part of routine care during the study period. 30 secondary or tertiary memory clinics in France. Clinicians indicated their diagnosis hypothesis and an estimate of their diagnostic confidence [scale 1-10]. Receiver operating characteristic (ROC) analysis, including the calculation of the area under the curve (AUC), was conducted using logistic regression to evaluate the diagnostic performance of CSF AD biomarkers. In 813 consecutive patients, median age 70 [interquartile range (IQR) = 63 - 77] including 132 patients over 80 years, we observed a similar confidence gain in CSF biomarkers between older and younger patients, both for AD and non-AD diagnoses. In older patients, the added value of CSF biomarkers was greater when CSF biomarkers indicated AD profile whereas the initial hypothesis was "non-AD", leading to a final diagnosis of AD (2.4 ± 1.6 versus 1.1 ± 2.1, p-value, p = 0.03). ROC analyses showed similar performance of AD CSF biomarkers in older and younger patients. CSF AD biomarkers added substantial value to clinical assessment in patients over 80. Their use seems crucial in the diagnostic process for older adults referred to memory clinics
