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Circadian copeptin and oxytocin profiles in anorexia nervosa: Exploring the interplay with neurohypophysis opioid tone
No full textInternational audienceContext Neurohypophysis (NH) function in eating disorders (ED) remains poorly elucidated. Studies on vasopressin and oxytocin display inconclusive findings regarding their levels and associations with psychological complications in ED. The profile of opioid tone, a crucial NH activity regulator, is also unknown. Objective To characterise the circadian profile of NH hormones and NH opioid tone using positron emission tomography/MRI (PET/MRI) imaging in patients with ED compared to healthy controls. Methods Twelve‐point plasma circadian profiles of copeptin and oxytocin, alongside nutritional and psychological scores, were assessed in age‐matched female participants: 13 patients with anorexia nervosa restrictive‐type (ANR), 12 patients recovered from AN (ANrec), 14 patients with bulimia nervosa and 12 controls. Neurohypophysis PET/MRI [ 11 C] diprenorphin binding potential (BP ND ) was evaluated in AN, ANrec and controls. Results Results revealed lower copeptin circadian levels in both ANR and ANrec compared to controls, with no oxytocin differences. Bulimia nervosa exhibited elevated copeptin and low oxytocin levels. [ 11 C] diprenorphin pituitary binding was fully localised in NH. Anorexia nervosa restrictive‐type displayed lower NH [ 11 C] diprenorphin BP ND (indicating higher opioid tone) and volume than controls. In ANR, copeptin inversely correlated with osmolarity. Neurohypophysis [ 11 C] diprenorphin BP ND did not correlated with copeptin or oxytocin. Conclusion Copeptin demonstrated significant group differences, highlighting its potential diagnostic and prognostic value. Oxytocin levels exhibited conflicting results, questioning the reliability of peripheral blood assessment. Increased NH opioid tone in anorexia nervosa may influence the vasopressin or oxytocin release, suggesting potential therapeutic applications
The spatial organization of cDC1 with CD8+ T cells is critical for the response to immune checkpoint inhibitors in melanoma patients
No full textInternational audienceAbstract Dendritic cells (DCs) are promising targets for cancer immunotherapies because of their central role in the initiation and control of immune responses. The rare cDC1 population is of particular interest because of its remarkable ability to cross-present antigens (Ag) to CD8+ T cells, to promote Th1 cell polarization and NK cell activation and recruitment. However, the spatial organization and specific functions of cDC1s in response to immunotherapy remain to be clearly characterized in human tumors. Here, we implemented a multiplexed immunofluorescence analysis pipeline coupled with computational image analysis to determine the spatial organization of the cDC1 subset in a cohort of skin lesions from advanced melanoma patients treated with immune checkpoint inhibitors (ICI). For this, we performed a whole-slide image analysis of cDC1 infiltration and distribution as well as their spatial interactions with key immune partners such as CD8+ T cells and pDC according to the response of patients to ICI. We also analyzed LAMP3+-DC, which correspond to a mature subset of tumor-infiltrating DCs. Distance and cell network analyses demonstrated that cDC1s exhibited a scattered distribution compared to tumor-infiltrating pDCs and LAMP3+-DCs, which were preferentially organized in dense areas with high homotypic connections. Interestingly, the proximity and interactions between CD8+ T cells and cDC1s were positively associated with the response to ICI. In conclusion, our study unravels the complex spatial organization of cDC1s and their interactions with CD8+ T cells in melanoma patient lesions, shedding light on their pivotal role in shaping the response to ICI
Enhancing Fluorescence Correlation Spectroscopy with machine learning to infer anomalous molecular motion
No full textInternational audienceThe random motion of molecules in living cells has consistently been reported to deviate from standard Brownian motion, a behavior coined as ``anomalous diffusion''. To study this phenomenon in living cells, Fluorescence Correlation Spectroscopy (FCS) and Single-Particle Tracking (SPT) are the two main methods of reference. In opposition to SPT, FCS with its classical analysis methodology cannot consider models of motion for which no analytical expression of the auto-correlation function is known. This excludes for instance anomalous Continuous-Time Random Walks (CTRW) and Random Walk on fractal (RWf). Moreover, the whole acquisition sequence of the classical FCS methodology takes several tens of minutes. Here, we propose a new analysis approach that frees FCS of these limitations. Our approach associates each individual FCS recording with a vector of features based on an estimator of the auto-correlation function and uses machine learning to infer the underlying model of motion and to estimate the values of the motion parameters. Using simulated recordings, we show that this approach endows FCS with the capacity to distinguish between a range of standard and anomalous random motions, including CTRW and RWf. Our approach exhibits performances comparable to the best-in-class state-of-the-art algorithms for SPT and can be used with a range of FCS setup parameters. Since it can be applied on individual recordings of short duration, we show that with our method, FCS can be used to monitor rapid changes of the motion parameters. Finally, we apply our method on experimental FCS recordings of calibrated fluorescent beads in increasing concentrations of glycerol in water. Our results accurately predict that the beads follow Brownian motion with a diffusion coefficient and anomalous exponent which agree with classical predictions from Stokes-Einstein law even at large glycerol concentrations. Taken together, our approach significantly augments the analysis power of FCS to capacities that are similar to state-of-the-art SPT approaches
Ixazomib, pomalidomide and dexamethasone in relapsed or refractory multiple myeloma characterized with high-risk cytogenetics: the IFM 2014-01 study
No full textInternational audienc
Long term noninvasive respiratory support in children with OSA-I and OSA-II: data of a nation-wide study
No full textInternational audiencePurposeThe aim of the study was to analyze the characteristics of otherwise healthy children with obstructive sleep apnea (OSA; OSA-I) and children with OSA and non-syndromic obesity (OSA-II) treated with long term continuous positive airway pressure (CPAP) or noninvasive ventilation (NIV) in 2019 in France.MethodsData were collected from a national survey on paediatric home noninvasive ventilatory support. CPAP/NIV initiation criteria and duration, age at CPAP/NIV initiation, equipment used and CPAP/NIV settings, and objective compliance were analyzed.ResultsPatients with OSA-I and OSA-II represented 6% (n=84, 71% males) and 10% (n=144, 72% males) of the national cohort, respectively. The apnea-hypopnea index (63% vs 76%), alone or combined with nocturnal gas exchange (25% vs 21%, for OSA-II and OSA-I patients respectively) were used as initiation criteria of CPAP/NIV. OSA-II patients were older at CPAP/NIV initiation (mean age 11.0±4.0 vs 6.8±4.5 years, p<0.001) and were treated for a longer time (2.3±2.6 vs 1.3±1.5 years, p=0.008) than OSA-I patients. NIV was used in 6% of OSA-I patients and 13% of OSA-II patients (p=0.142). Both groups used preferentially a nasal mask. Mean CPAP level was higher in OSA-II patients as compared to OSA-I patients (8.7±2.0 vs 7.7±2.4 cmH2O, p=0.02). Objective compliance was comparable (mean use 6.8±2.6 vs 5.9±3.0 hours/night in OSA-I and OSA-II, respectively, p=0.054).ConclusionSix and 10% of children treated with long term CPAP/NIV in France in 2019 had OSA-I and OSA-II, respectively. Both groups were preferentially treated with CPAP and were comparable except for age, with OSA-II patients being older at CPAP/NIV initiation
Redefining the Concept of Patellofemoral Stuffing in Total Knee Arthroplasty
No full textInternational audienceIntroductionBalancing the patellofemoral joint (PFJ) in total knee arthroplasty (TKA) involves avoiding over-stuffing. The purpose of this study was to assess how often a strategy of recreating the anterior space of the trochlea (full extension) led to the trochlea depth being recreated in both mid-flexion (30–40°) and deep flexion (80–90°).MethodsOne hundred and twenty two consecutive patients undergoing robotic-assisted TKA had femoral components placed according to functional alignment principals and were assessed. The femoral component was sized and positioned in order to ensure that the anterior flange was within 2 mm of the native anatomy, corresponding to a patella position of full extension (0° flexion). Trochlea depth restoration in 3 positions along the floor of the trochlea groove was compared and measured. The trochlea was defined as balanced if the prosthesis was within 2 mm of the native anatomy. Patients were divided into over-stuffed (prosthesis >2 mm above the native anatomy) or under-stuffed (prosthesis >2 mm beneath the native anatomy).ResultsAll patients 122/122 (100%) had a balanced trochlea in full extension. In total 54 TKA were over or under-stuffed at either mid-flexion or deep flexion. In mid-flexion, 3/122 (2.5%) trochlea were over-stuffed and 39/122 (32%) trochlea were under-stuffed. In deep flexion, 25/122 (20.5%) of trochlea’s were overstuffed and 30/122 (24.6%) were under-stuffed. In mid-flexion, balanced trochlea components were more externally rotated relative to the posterior condylar axis compared to unbalanced components (2.35° external rotation vs 1.21°, p=0.004). There were no other significant differences observed between the balanced and unbalanced trochlea groups in mid or deep flexion.ConclusionOver 40% of TKA over or under-stuff the trochlea in deeper flexion despite the anterior flange being positioned within 2 mm of the native anatomy in full extension. The rate of over or under-stuffing in mid and deep flexion was similar (>40%); however, in mid-flexion, under-stuffing of the native trochlea was more common. The concept of PFJ over or under-stuffing in TKA needs to be redefined to consider the full arc of flexion of the trochlea groove, and the biomechanical and clinical consequences of under-stuffing the trochlea investigated further.EvidenceLevel IV
Most babies born at a French hospital before 26 weeks survived with good outcomes
No full textInternational audienceAim The aim of this French study was to determine the neonatal morbidity, mortality and neurodevelopmental outcomes when infants born at the limit of viability reached 2 years of corrected age. We then compared the results with national and international cohorts. Methods This study focused on 294 French infants born from 22 to 25 weeks of gestation in a single tertiary perinatal centre from January 2010 to December 2019. We used data on neonatal mortality and morbidity to calculate the survival rates of infants without moderate to severe neurodevelopmental and sensory deficits at 2 years of corrected age. These outcomes were compared with data from contemporary epidemiological studies of similar populations. Results Nearly two‐thirds (60.5%) of the infants survived to discharge, with varying rates based on their gestational ages, and 57.3% had no severe neonatal morbidity. The vast majority (90.4%) of the 166 alive and available at 2 years of corrected age were free of moderate to severe neurodevelopmental impairment. Our survival rates exceeded a national French cohort study, but were closely aligned with international cohorts. Conclusion These findings highlight the importance of incorporating local data into ethical decision‐making about life‐saving treatment for infants at the limit of viability
Intrarectal Injections of Botulinum Toxin for the Treatment of Urge Fecal Incontinence: Long-Term Results of an FI-Toxin Cohort Study
No full textInternational audienceBackground: The efficacy and safety of intrarectal botulinum toxin A (BoNT/A) injections in patients with urge fecal incontinence (FI) were evidenced in a large, multicenter, randomized, placebo-controlled study (FI-TOXIN). The aims of the present study were to evaluate the long-term efficacy and safety of intrarectal BoNT/A injections in a real-world setting in patients who participated in the FI-TOXIN study.Methods: Data collected from patients who had previously participated in the FI-TOXIN study in 8 French centers from November 2015 to November 2020 were retrospectively analyzed. Given the transient effect of BoNT/A, patients who had received the first injection in the FI-TOXIN study could be re-injected if symptoms recurred. Information on re-injections, satisfaction of patients, severity of FI symptoms, adverse effects, and the switch to another treatment was retrospectively collected from medical charts between M6 (end of the double-blind phase) and M54 of the inclusion in the FI-TOXIN study.Key results: Of the 191 patients in the initial FI-TOXIN cohort, 147 (77.0%) were included at M6. Between M6 and M54, 114 of these patients received 233 injections (68 first injections, 165 re-injections). Satisfaction information was available for 70 patients, of whom 43/70 (61.4%) were satisfied with all their injections. The treatment failed in 52/147 (35.4%) of the patients, with rejections of the treatment by patients due to insufficient perceived efficacy (34 patients), adverse effects or poor tolerance (11 patients), or switch to a surgical treatment (23 patients). Nonsevere adverse events were recorded after 45/233 (19.3%) injections. The two severe adverse events (cervical cancer and psychiatric hospitalization) were unrelated to the treatment.Conclusions: Intrarectal injections of BoNT/A displayed moderate long-term efficacy without major adverse effects
Umbrella Review and Meta-Analysis: The Efficacy of Nonpharmacological Interventions for Sleep Disturbances in Children and Adolescents
No full textInternational audienceWe conducted an umbrella review of systematic reviews (SRs), with or without meta-analysis (MA), of randomized controlled trials (RCTs) assessing nonpharmacological sleep interventions for children and adolescents across various clinical populations
