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Background/Objectives : Chronic low back pain (CLBP) is a common condition with limited long-term treatment options. Vagus nerve stimulation (VNS) has shown potential for pain improvement, but its use in CLBP remains underexplored. Our aim was to evaluate the efficacy, feasibility and tolerability of transcutaneous auricular vagus nerve stimulation (taVNS) in reducing pain and improving functional outcomes in CLBP patients. Methods : Thirty adults with CLBP (VAS ≥ 40/100) participated in this open-label pilot study (NCT05639270). Patients were treated with a taVNS device on the left ear for 30 min daily over a period of 3 months. The primary outcome was a reduction in pain intensity (VAS) at 1 month. Secondary outcomes included pain intensity at 3 months, disability (Oswestry Disability Index, ODI), quality of life (EQ-5D-5L), catastrophizing and psychological distress. In addition, compliance and adverse events were monitored. Results : After 1 month, 27 patients were evaluated. VAS scores decreased significantly by 16.1 (SD = 17.9) mm ( p < 0.001) and by 22.5 (25) mm ( p < 0.001) after 3 months (24 patients were analyzed). Functional disability improved with an average reduction in ODI of 11.9 (11.1) points ( p < 0.001) after 3 months. Other patient-reported outcomes also improved significantly over the 3-month period. Overall, 51.9% of the patients achieved clinically meaningful pain reduction (≥20 mm), and no serious adverse events were reported. Treatment adherence was good, with half of the patients achieving 80% adherence. Conclusions : This pilot study suggests that taVNS is a feasible, safe and potentially effective treatment for CLBP that warrants further investigation in a randomized controlled trial compared to sham stimulation.

Objectives: To assess the efficacy of a single intradiscal injection of allogeneic bone marrow mesenchymal stromal cells (BM-MSCs) versus a sham placebo in patients with chronic low back pain (LBP)., Methods: Participants were randomised in a prospective, double-blind, controlled study to receive either sham injection or intradiscal injection of 20 million allogeneic BM-MSC, between April 2018 and December 2022. The first co-primary endpoint was the rate of responders defined by improvement of the Visual Analogue Scale (VAS) for pain of at least 20% and 20 mm, or improvement of the Oswestry Disability Index (ODI) of 20% between baseline and month 12. The secondary structural co-primary endpoint was assessed by the disc fluid content measured by quantitative MRI T2, between baseline and month 12. Secondary endpoints included pain VAS, ODI, the Short Form (SF)-36 and the minimal clinically important difference in all timepoints (1, 3, 6, 12 and 24 months). We determined the immune response associated with allogeneic cell injection between baseline and 6 months. Serious adverse events (SAEs) were recorded., Results: 114 patients were randomised (n=58, BM-MSC group; n=56, sham placebo group). At 12 months, the primary outcome was not reached (74% in the BM-MSC group vs 69% in the placebo group; p=0.77). The groups did not differ in all secondary outcomes. No SAE related to the intervention occurred., Conclusions: While our study did not conclusively demonstrate the efficacy of allogeneic BM-MSCs for LBP, the procedure was safe. Long-term outcomes of MSC therapy for LBP are still being studied., Trial Registration Number: EudraCT 2017-002092-25/ClinicalTrials.gov: NCT03737461., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ on behalf of EULAR.)

Introduction: Current recommendations preconize prophylactic mastectomy for women over 30 with increased risk of breast cancer. Several surgical techniques are available to perform bilateral mastectomy with or without breast reconstruction. Our primary objective was to evaluate the feasibility of the Endoscopic Nipple Sparing Mastectomy (E-NSM) technique, without robotic assistance, using a single axillary incision and with immediate reconstruction using a prepectoral prosthesis in prophylactic indications. The secondary objectives were to evaluate the risks of postoperative complications and the esthetic results., Material and Methods: This is a preliminary report of a prospective single-center interventional clinical study with a final enrolment target of 20 patients. The primary endpoint was the rate of complete surgical procedures per E-NSM. The secondary endpoints were the rate of conversions to conventional surgery, infections, hematomas, skin injury, pain and esthetic results (Breast-Q questionnaire, additional cosmetic procedures)., Results: From April 2019 to June 2022, 10 patients were included for 19 procedures (9 bilateral mastectomies, 1 unilateral). All surgical procedures were complete; no conversion to conventional surgery was required. The rate of complications per procedure requiring revision surgery was 16 % (1 skin necrosis, 1 postoperative hematoma and 1 surgical site infection). No prosthesis was removed. The seroma rate was 5 %. All patients would recommend this technique and were very satisfied or satisfied with the esthetic result. A second cosmetic procedure (lipofilling) was necessary in 50 % of patients., Discussion: These preliminary data attest to the feasibility and safety of the E-NSM approach, and should be confirmed on a larger cohort and longer-term follow-up., Gov Identifier: NCT03838549., Competing Interests: Disclosure of interests The corresponding author is consultancy for Applied Medical, that's the only conflict of interest to disclose., (Copyright © 2024. Published by Elsevier Masson SAS.)

Background: Serum neurofilament light chain (sNfL) and glial fibrillary acidic protein (sGFAP) are promising biomarkers that might be associated with clinical and radiological markers of multiple sclerosis (MS) severity. However, it is not known whether they can accurately identify patients at risk of disability progression in the medium and long term., Objectives: We wanted to determine the association between sNfL and sGFAP, Expanded Disability Status Scale score changes, and conversion to secondary progressive MS (SPMS) in a cohort of 133 patients with relapsing remitting MS., Methods: Blood samples were collected at inclusion to measure SNfL and sGFAP by single molecule array and their prognostic value was assessed using a linear mixed model., Results: In this cohort, 37 patients (27.8 % of 133) experienced disability progression and 12 patients (9.0 %) converted to SPMS during the follow-up (mean follow-up duration: 6.4 years). Only sNfL (p = 0.03) was associated with conversion to SPMS, and neither SNfL nor sGFAP was associated with disability progression., Conclusion: Serum NfL and GFAP do not seem to accurately predict MS outcome in the long term. More studies are needed to determine how serum biomarkers, associated with other clinical and MRI biomarkers, might be used to improve MS prognostication., Competing Interests: Declaration of competing interest None., (Copyright © 2024. Published by Elsevier B.V.)

Chronic pain exerts a significant impact on the quality of life, giving rise to both physical and psycho-social vulnerabilities. It not only leads to direct costs associated with treatments, but also results in indirect costs due to the reduced productivity of affected individuals. Chronic conditions can be improved by reducing modifiable risk factors. Various educational programs, including the Chronic Disease Self-Management Programme (CDSMP), have demonstrated the advantages of enhancing patient empowerment and health literacy. Nevertheless, their efficacy in addressing pain symptoms has received limited attention, especially concerning vulnerable populations. This research aims to assess the effectiveness of the CDSMP in alleviating pain among socio-economically vulnerable participants with chronic conditions. By accounting for a wide range of variables, and using data from the EFFICHRONIC project (EU health programme), we investigated the changes in pain levels after the intervention, among 1070 participants from five European countries. Our analyses revealed a significant reduction in pain following the intervention. This finding supports the notion that training programs can effectively ameliorate pain and alleviate its impact on the quality of life, particularly in vulnerable populations. Younger participants, as well as those with higher education levels and individuals experiencing higher levels of pain at baseline, were more likely to experience a reduction in their pain levels. These findings underscore the importance of recognising the social determinants of health. The study was registered at ClinicalTrials.gov (ISRCTN70517103)., (© 2024 The Authors. The International Journal of Health Planning and Management published by John Wiley & Sons Ltd.)

Background: The PRADO-IC (Programme de Retour à Domicile après une Insuffisance Cardiaque) is a transition care program designed to improve the coordination of care between hospital and home that was generalized in France in 2014. The PRADO-IC consists of an administrative assistant who visits patients during hospitalization to schedule follow-up visits. The aim of the present study was to evaluate the PRADO-IC program based on the hypotheses provided by health authorities., Methods and Results: The PRADOC study is a multicenter, controlled, randomized, open-label, mixed-method trial of the transition program PRADO-IC versus usual management in patients hospitalized with heart failure (standard of care group; NCT03396081). A total of 404 patients were recruited between April 2018 and May 2021. The mean patient age was 75 years (±12 years) in both groups. The 2 groups were well balanced regarding severity indices. At discharge, patients homogeneously received the recommended drugs. There was no difference between groups regarding hospitalizations for acute heart failure at 1 year, with 24.60% in the standard of care group and 25.40% in the PRADO-IC group during the year following the index hospitalization (hazard ratio, 1.04 [95% CI, 0.69-1.56]; P =0.85) or cardiovascular mortality (hazard ratio, 0.67 [95% CI, 0.34-1.31]; P =0.24)., Conclusions: The PRADO-IC has not significantly improved clinical outcomes, though a trend toward reduced cardiovascular mortality is evident. These results will help in understanding how transitional care programs remain to be integrated in pathways of current patients, including telemonitoring, and to better tailor individualized approaches., Registration: URL: https://www.clinicaltrials.gov; Unique Identifier: NCT03396081.

Introduction: Education is recognised as an effective and necessary approach in chronic low back pain. Nevertheless, data regarding the effectiveness of education in promoting physical activity in the medium term or long term are still limited, as are the factors that could lead to successful outcomes. Our study aims to assess the effectiveness of a pain neuroscience education programme compared with traditional back school on physical activity 3 months and 1 year after educational sessions coupled with a multidisciplinary rehabilitation programme. Additionally, we seek to evaluate the effects of these educational interventions on various factors, including pain intensity and psychobehavioural factors. Finally, our goal is to identify the determinants of success in educational sessions combined with the rehabilitation programme., Methods and Analysis: The study will involve 82 adults with chronic low back pain. It will be a monocentric, open, controlled, randomised, superiority trial with two parallel arms: an experimental group, 'pain neuroscience education', and a control group, 'back school'. The primary outcome is the average number of steps taken at home over a week, measured by an actigraph. Secondary outcomes include behavioural assessments. Descriptive and inferential analysis will be conducted. Multivariate modelling will be performed using actimetric data and data from the primary and secondary outcomes., Ethics and Dissemination: The Committee for Personal Protection of Ile de France VII (CPP) gave a favourable opinion on 22 June 2023 (National number: 2023-A00346-39). The study was previously registered with the National Agency for the Safety of Medicines and Health Products (IDRCB: 2023-A00346-39). Participants signed an informed consent during the inclusion visit. This protocol is the version submitted to the CPP entitled 'Protocol Version N°1 of 03/29/2023'. The results of the study will be presented nationally and internationally through conferences and publications., Trial Registration Number: NCT05840302., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: According to the World Health Organization, climate and ecological emergencies are already major threats to human health. Unabated climate change will cause 3.4 million deaths per year by the end of the century, and health-related deaths in the population aged ≥65 years will increase by 1540%. Planetary health (PH) is based on the understanding that human health and human civilization depend on flourishing natural systems and the wise stewardship of those natural systems. Health care systems collectively produce global emissions equivalent to those of the fifth largest country on earth, and they should take steps to reduce their environmental impact. Primary care in France accounts for 23% of greenhouse gas emissions in the health care sector. General practitioners (GPs) have an important role in PH. The course offers first-year GP residents of the Montpellier-Nîmes Faculty of Medicine a blended-learning course on environmental health. An e-learning module on PH, lasting 30 to 45 minutes, has been introduced in this course., Objective: The objective of this study was to assess the impact of the e-learning module on participants' knowledge and behavior change., Methods: This was a before-and-after study. The module consisted of 3 parts: introduction, degradation of ecosystems and health (based on the Intergovernmental Panel on Climate Change report and planetary limits), and ecoresponsibility (based on the Shift Project report on the impact of the health care system on the environment). The questionnaire used Likert scales to self-assess 10 points of knowledge and 5 points of PH-related behavior., Results: A total of 95 participants completed the pre- and posttest questionnaires (response rate 55%). The mean scores for participants' pretest knowledge and behaviors were 3.88/5 (SD 0.362) and 3.45/5 (SD 0.705), respectively. There was no statistically significant variation in the results according to age or gender. The pretest mean score of participants who had already taken PH training was statistically better than those who had not taken the PH training before this course (mean 4.05, SD 0.16 vs mean 3.71, SD 0.374; P<.001)., Conclusions: The PH module of the Primary Care Environment and Health course significantly improved self-assessment knowledge scores and positively modified PH behaviors among GP residents. Further work is needed to study whether these self-declared behaviors are translated into practice., (©Cédric Tourrette, Jean-Baptiste Tostain, Eva Kozub, Maha Badreddine, Julia James, Aurore Noraz, Charlotte De Choudens, Lionel Moulis, Claire Duflos, Francois Carbonnel. Originally published in JMIR Formative Research (https://formative.jmir.org), 14.05.2024.)

Background: Skin cancers are the most common group of cancers diagnosed worldwide. Aging and sun exposure increase their risk. The decline in the number of dermatologists is pushing the issue of dermatological screening back onto family doctors. Dermoscopy is an easy-to-use tool that increases the sensitivity of melanoma diagnosis by 60% to 90%, but its use is limited due to lack of training. The characteristics of "ideal" dermoscopy training have yet to be established. We created a Moodle (Moodle HQ)-based e-learning course to train family medicine residents in dermoscopy., Objective: This study aimed to evaluate the evolution of dermoscopy knowledge among family doctors immediately and 1 and 3 months after e-learning training., Methods: We conducted a prospective interventional study between April and November 2020 to evaluate an educational program intended for family medicine residents at the University of Montpellier-Nîmes, France. They were asked to complete an e-learning course consisting of 2 modules, with an assessment quiz repeated at 1 (M1) and 3 months (M3). The course was based on a 2-step algorithm, a method of dermoscopic analysis of pigmented skin lesions that is internationally accepted. The objectives of modules 1 and 2 were to differentiate melanocytic lesions from nonmelanocytic lesions and to precisely identify skin lesions by looking for dermoscopic morphological criteria specific to each lesion. Each module consisted of 15 questions with immediate feedback after each question., Results: In total, 134 residents were included, and 66.4% (n=89) and 47% (n=63) of trainees fully participated in the evaluation of module 1 and module 2, respectively. This study showed a significant score improvement 3 months after the training course in 92.1% (n=82) of participants for module 1 and 87.3% (n=55) of participants for module 2 (P<.001). The majority of the participants expressed satisfaction (n=48, 90.6%) with the training course, and 96.3% (n=51) planned to use a dermatoscope in their future practice. Regarding final scores, the only variable that was statistically significant was the resident's initial scores (P=.003) for module 1. No measured variable was found to be associated with retention (midtraining or final evaluation) for module 2. Residents who had completed at least 1 dermatology rotation during medical school had significantly higher initial scores in module 1 at M0 (P=.03). Residents who reported having completed at least 1 dermatology rotation during their family medicine training had a statistically significant higher score at M1 for module 1 and M3 for module 2 (P=.01 and P=.001)., Conclusions: The integration of an e-learning training course in dermoscopy into the curriculum of FM residents results in a significant improvement in their diagnosis skills and meets their expectations. Developing a program combining an e-learning course and face-to-face training for residents is likely to result in more frequent and effective dermoscopy use by family doctors., (©Pauline Friche, Lionel Moulis, Aurélie Du Thanh, Olivier Dereure, Claire Duflos, Francois Carbonnel. Originally published in JMIR Formative Research (https://formative.jmir.org), 13.05.2024.)

Background: Environmental and behavioral factors are responsible for 12.6 million deaths annually and contribute to 25% of deaths and chronic diseases worldwide. Through the One Health initiative, the World Health Organization and other international health organizations plan to improve these indicators to create healthier environments by 2030. To meet this challenge, training primary care professionals should be the priority of national policies. General practitioners (GPs) are ready to become involved but need in-depth training to gain and apply environmental health (EH) knowledge to their practice. In response, we designed the Primary Care Environment and Health (PCEH) online course in partnership with the Occitanie Regional Health Agency in France. This course was used to train GP residents from the Montpelier-Nimes Faculty of Medicine in EH knowledge. The course was organized in 2 successive parts: (1) an asynchronous e-learning modular course focusing on EH knowledge and tools and (2) 1 day of face-to-face sessions., Objective: This study assessed the impact of the e-learning component of the PCEH course on participants' satisfaction, knowledge, and behavior changes toward EH., Methods: This was a pilot before-and-after study. Four modules were available in the 6-hour e-learning course: introduction to EH, population-based approach (mapping tools and resources), clinical cases, and communication tools. From August to September 2021, we recruited first-year GP residents from the University of Montpellier (N=130). Participants' satisfaction, knowledge improvements for 19 EH risks, procedure to report EH risks to health authorities online, and behavior change (to consider the possible effects of the environment on their own and their patients' health) were assessed using self-reported questionnaires on a Likert scale (1-5). Paired Student t tests and the McNemar χ 2 test were used to compare quantitative and qualitative variables, respectively, before and after the course., Results: A total of 74 GP residents completed the e-learning and answered the pre- and posttest questionnaires. The mean satisfaction score was 4.0 (SD 0.9) out of 5. Knowledge scores of EH risks increased significantly after the e-learning course, with a mean difference of 30% (P<.001) for all items. Behavioral scores improved significantly by 18% for the participant's health and by 26% for patients' health (P<.001). These improvements did not vary significantly according to participant characteristics (eg, sex, children, place of work)., Conclusions: The e-learning course improved knowledge and behavior related to EH. Further studies are needed to assess the impact of the PCEH course on clinical practice and potential benefits for patients. This course was designed to serve as a knowledge base that could be reused each year with a view toward sustainability. This course will integrate new modules and will be adapted to the evolution of EH status indicators and target population needs., (©Jean-Baptiste Tostain, Marina Mathieu, Agnès Oude Engberink, Bernard Clary, Michel Amouyal, Béatrice Lognos, Pascal Demoly, Isabella Annesi-Maesano, Grégory Ninot, Nicolas Molinari, Arnaud Richard, Maha Badreddine, Claire Duflos, Francois Carbonnel. Originally published in JMIR Formative Research (https://formative.jmir.org), 09.05.2024.)

Background: Poliomyelitis is a global disabling disease affecting 12-20 million of people. Post poliomyelitis syndrome (PPS) may affect up to 80% of polio survivors: increased muscle weakness, pain, fatigue, functional decline. It relies on aging of an impaired neuro-muscular system with ongoing denervation processes. A late involvement of humoral or cellular pro-inflammatory phenomena is also suspected., Aim: To assess the dysimmune hypothesis of PPS by comparing lymphocyte subpopulations and humoral immune factors between PPS patients and controls., Design: Cross-sectional study., Setting: Montpellier University Hospital., Population: Forty-seven PPS and 27 healthy controls., Methods: PPS patients and controls were compared on their lymphocyte subpopulations and humoral immune factors (IL-1β, IL-6, IL-8, IL-17, IL-21, IL-22, IL-23, IFN-γ, TNF-α, GM-CSF, RANTES, MCP1, MIP-3a, IL-10, TGF-β, IL4, IL13). Patients were further compared according to their dominant clinical symptoms. Sample size guaranteed a power >90% for all comparisons., Results: PPS patients and controls were comparable in gender, age and corpulence. Most patients had lower limb motor sequelae (N.=45, 95.7%), a minority had upper limb motor impairment (N.=16, 34.0%). Forty-five were able to walk (94%), 35/45 with technical aids. The median of the two-minute walking test was 110 meters (interquartile range 55; 132). Eighteen (38%) required help in their daily life. Their quality of life was low (SF36). All described an increased muscular weakness, 40 (85%) a general fatigue, and 39 (83%) muscular or joint pain. Blood count, serum electrolytes, T and B lymphocyte subpopulations and cytokines were comparable between patients and controls, except for creatine phospho kinase that was significantly higher in PPS patients. None of these variables differed between the 20/47 patients whose late main symptoms were pain or fatigue, and other patients., Conclusions: Our results suggest that PPS is not a dysimmune disease., Clinical Rehabilitation Impact: Our results do not sustain immunotherapy for PPS. Our work suggest that PPS may be mostly linked to physiological age-related phenomena in a disabled neuromuscular condition. Thus, our results emphasize the role of prevention and elimination of aggravating factors to avoid late functional worsening, and the importance of rehabilitation programs that should be adapted to patients' specific conditions.

A personalized 3D breast model could present a real benefit for preoperative discussion with patients, surgical planning, and guidance. Breast tissue biomechanical properties have been poorly studied in vivo, although they are important for breast deformation simulation. The main objective of our study was to determine breast skin thickness and breast skin and adipose/fibroglandular tissue stiffness. The secondary objective was to assess clinical predictors of elasticity and thickness: age, smoking status, body mass index, contraception, pregnancies, breastfeeding, menopausal status, history of radiotherapy or breast surgery. Participants were included at the Montpellier University Breast Surgery Department from March to May 2022. Breast skin thickness was measured by ultrasonography, breast skin and adipose/fibroglandular tissue stiffnesses were determined with a VLASTIC non-invasive aspiration device at three different sites (breast segments I-III). Multivariable linear models were used to assess clinical predictors of elasticity and thickness. In this cohort of 196 women, the mean breast skin and adipose/fibroglandular tissue stiffness values were 39 and 3 kPa, respectively. The mean breast skin thickness was 1.83 mm. Only menopausal status was significantly correlated with breast skin thickness and adipose/fibroglandular tissue stiffness. The next step will be to implement these stiffness and thickness values in a biomechanical breast model and to evaluate its capacity to predict breast tissue deformations., (© 2024 The Authors. Clinical Anatomy published by Wiley Periodicals LLC on behalf of American Association of Clinical Anatomists and British Association of Clinical Anatomists.)

Introduction: Hormone therapy (HT) is a major adjuvant treatment for breast cancer. Despite their effectiveness, aromatase inhibitors can cause several side effects, including arthralgia in 35%-50% of patients. These side effects frequently lead to the premature discontinuation of HT. Whole-body cryotherapy (WBC) can be used for managing arthritic pain. The primary objective of this study will be to evaluate the effect of WBC on aromatase-induced joint pain, compared with placebo cryotherapy, in patients with hormone-dependent breast cancer receiving adjuvant aromatase inhibitors. The secondary objectives will be to evaluate WBC safety and its effect on analgesic consumption, HT adherence and quality of life., Methods and Analysis: In this randomised, placebo-controlled, double-blinded clinical trial, 56 patients with aromatase inhibitor-induced joint pain and a Brief Pain Inventory-Short Form (BPI-SF) score ≥3 for the worst pain experienced in the previous week will be randomised into the WBC or placebo cryotherapy arm (10 sessions in each group). The primary outcome will be the BPI-SF score at week 6 post-treatment. The secondary outcomes will include the BPI-SF scores at months 3 and 6 post-treatment, the BPI-SF pain severity index and pain interference index, the Health Assessment Questionnaire score, the number of days of aromatase inhibitor treatment and analgesic consumption in the 15 days before the visits at week 6 and months 3 and 6 after cryotherapy. The incidence of adverse events will also be investigated., Ethics and Dissemination: Ethics approval was obtained from the Ethics Committee Est IV of Hospital Civil, Strasbourg, France. Protocol V.5 was approved in December 2022. The results will be disseminated in a peer-reviewed journal and presented at international congresses., Trial Registration Number: NCT05315011., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Reversible cerebral vasoconstriction syndrome (RCVS) is a rare, but increasingly recognised cerebrovascular condition with an estimated annual age-standardised incidence of approximately three cases per million. Knowledge about risk factors and triggering conditions and information about prognosis and optimal treatment in these patients are limited., Methods: The REversible cerebral Vasoconstriction syndrome intERnational CollaborativE (REVERCE) project aims to elucidate the epidemiological and clinical characteristics of RCVS by collecting individual patient data from four countries (France, Italy, Taiwan and South Korea) in the setting of a multicentric study. All patients with a diagnosis of definite RCVS will be included. Data on the distribution of risk factors and triggering conditions, imaging data, neurological complications, functional outcome, risk of recurrent vascular events and death and finally the use of specific treatments will be collected. Subgroup analyses will be made based on age, gender, aetiology, ethnicity and geographical region of residence., Ethics and Dissemination: Ethical approval for the REVERCE study will be obtained from national or local institutional review boards in the participating centres. When needed, a standardised data transfer agreement will be provided for participating centres. We plan dissemination of our results in peer-reviewed international scientific journals and through conference presentations. We expect that the results of this unique study will lead to better understanding of clinical and epidemiological characteristics of RCVS patients., Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: The authors do not have any conflicts of interest related to the submitted work. KSL reports personal fees (Teva, Acticor Biotech). JM reports personal fees (Abbvie, GEP Sante, Lundbeck, Homeperf, Teva, Lilly, Lundbeck, Pfizer). MJL reports personal fees (Eli Lilly, Lundbeck, Pfizer, NuEyne Co., Teva, Abbvie, SK chemical, CKD Pharm, YuYu Pharma), research grants (Eli Lilly, Otsuka, Novartis, Allergan, BioHaven, Lundbeck, Eli Lilly/Ildong), and funding Seoul National University New Faculty Startup Fund, National Research Foundation of Korea grant funded by the Korea Government (MSIP) Yuhan company). AD reports personal fees (Allergan Abbvie, Lilly, Teva, Lundbeck, Pfizer, SOS). SJW reports personal fees (AbbVie, Pfizer, Eli Lilly, Biogen), research grants (Eli Lilly, Novartis) and has been principal investigator in sponsored trials (Novartis, Lundbeck and Orient Europharma). The other authors have nothing to disclose.

Aims: Diabetic foot ulcer (DFU) has a poor prognosis and high amputation rate. We previously used the French National Health Data System (Système National des Données de Santé: SNDS) to analyze the impact of deprivation and healthcare access on DFU prognosis. The purpose of this ancillary study was to explore the relationship between the global care pathway (care consumption) the year before and after DFU and the risk of amputation., Methods: We conducted a study based on a cohort from the SNDS. The data came from a region of France and subjects living with a complication of DFU. We looked at care consumption one year before and one year after wound onset. Risk of amputation was calculated one year after DFU onset., Results: Data were extracted for 6,642 patients. Subjects with DFU had a better prognosis regarding amputation risk when they are taking cardiovascular, antibiotic, neurological, drugs. A consultation with an ophthalmologist was also linked to a better prognosis: HR = 0.71 IC95 (0.499-0.995) (p = 0.04)., Conclusion: People with the best diabetes follow-up, even with several comorbidities, appear to have a better prognosis for their DFU. This highlights the importance of global healthcare and the care pathway in this chronic disease., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Background: Extended interval dosing (ED) for inhibitors of programmed cell death protein 1 (anti-PD-1) (nivolumab, pembrolizumab) or its ligand (anti-PD-L1) (durvalumab) were recently approved based on pharmacokinetic model results that predicted a benefit-risk profile comparable with the standard dosing (SD) regimen. However, safety data in real-world condition of use are lacking. The objective was to compare the incidence and the risk factors of serious immune-related adverse events (irAEs) and any-grade irAEs between the SD and ED regimens in patients treated with anti-PD-1 or anti-PD-L1., Materials and Methods: IrAEs were assessed from medical records in all new users of nivolumab, pembrolizumab, or durvalumab between 1 January 2019 and 31 December 2020 across two oncology centers in France. The incidence of irAEs was compared between both dosing regimens using Cox proportional hazards models adjusting for the main available confounders., Results: Among 686 patients included, 63% were new users of an SD regimen, 14% of ED regimen, and 23% started with SD and switched to ED regimen during follow-up. Overall, 34.6% of patients experienced at least one irAE of any grade and 11.4% presented at least one serious grade ≥3 irAE. No statistical difference was found between the SD and ED regimen on the risk of grade ≥3 irAEs [adjusted hazard ratio (HR) 1.40, 95% confidence interval (CI) 0.71-2.76] but our results suggest an increased risk of any-grade irAEs with the ED regimen (adjusted HR 1.46, 95% CI 1.00-2.12, P = 0.048). IrAEs resolved without sequelae in 46.4% of cases, and they were fatal for three patients (0.4%). Autoimmune pre-existing condition was confirmed as a risk factor for grade ≥3 irAEs (HR 2.56, 95% CI 1.53-4.27) and for all-grade irAEs (HR 1.60, 95% CI 1.17-2.20)., Conclusions: In a real-world setting, according to the regimen chosen by the oncologist based on clinical characteristics, we did not observe an increase in grade ≥3 irAE incidence between the SD and ED regimens., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: Reversible cerebral vasoconstriction syndrome (RCVS) has a heterogenous clinical and radiological presentation. We investigated whether RCVS complications vary according to age., Patients and Methods: In a pooled French cohort of 345 patients with RCVS, we assessed (1) rates of clinical and radiological complications, and (2) the functional outcome at 3 months according to age as a continuous variable, and in young patients aged ≤ 49 years versus those aged ≥ 50 years. The Commission Nationale Informatique et Liberté and the local ethics committee approved this study (registration number: 202100733)., Results: The risk for any focal deficit and for any brain lesion were independently associated with increasing age (OR 1.4, 95% CI 1.1-1.8; p = 0.014, and OR 1.6, 95% CI 1.2-2.1; p < 0.001, respectively). Subtypes of brain lesions independently associated with increasing age were subarachnoid haemorrhage (OR 1.7, 95% CI 1.3-2.3; p < 0.001) and intracerebral haemorrhage (OR 1.5, 95% CI 1.1-2.2; p = 0.023). Frequency of cervical artery dissections peaked at age 30-39, and young age was independently associated with cervical artery dissections (OR 13.6, 95% CI 2.4-76.6; p = 0.003). Age had no impact on the functional outcome, with a modified Rankin scale score of 0-1 in > 96% of patients., Conclusion: Age seems to influence rates and types of complications of RCVS, with young age being associated with cervical artery dissections, and increasing age with haemorrhagic complications. If confirmed in larger prospective studies, recognition of age-specific patterns might help to guide clinical management and to identify complications in cases of RCVS and vice versa., (© 2023. The Author(s).)

Background and Objectives: Chimeric antigen receptor (CAR) T-cell therapies have dramatically improved the prognosis of patients with relapsed or refractory hematologic malignancies; however, cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome (ICANS) occur in ∼100 and 50% of patients, respectively. This study aimed to determine whether EEG patterns may be considered as diagnostic tools for ICANS., Methods: Patients who received CAR T-cell therapy at Montpellier University Hospital between September 2020 and July 2021 were prospectively enrolled. Neurologic signs/symptoms and laboratory parameters were monitored daily for 14 days after CAR T-cell infusion. EEG and brain MRI were performed between day 6 and 8 after CAR T-cell infusion. EEG was performed again on the day of ICANS occurrence, if outside this time window. All collected data were compared between patients with and without ICANS., Results: Thirty-eight consecutive patients were enrolled (14 women; median age: 65 years, interquartile range: [55-74]). ICANS was observed in 17 of 38 patients (44%) after a median time of 6 days after CAR T-cell infusion (4-8). The median ICANS grade was 2 (1-3). Higher C-reactive protein peak (146 mg/L [86-256], p = 0.004) at day 4 (3-6), lower natremia (131 mmol/L [129-132], p = 0.005) at day 5 (3-6), and frontal intermittent rhythmic delta activity (FIRDA, p < 0.001) on EEG between days 6 and 8 after infusion were correlated with ICANS occurrence. FIRDA was only observed in patients with ICANS (N = 15/17, sensitivity of 88%) and disappeared after ICANS resolution, usually after steroid therapy. Except for hyponatremia, no other toxic/metabolic marker was associated with FIRDA ( p = 0.002). The plasma concentration of copeptin, a surrogate marker of antidiuretic hormone secretion, assessed at day 7 after infusion, was significantly higher in patients with (N = 8) than without (N = 6) ICANS ( p = 0.043)., Discussion: FIRDA is a reliable diagnostic tool for ICANS, with a sensitivity of 88% and a negative predictive value of 100%. Moreover, as this EEG pattern disappeared concomitantly with ICANS resolution, FIRDA could be used to monitor neurotoxicity. Finally, our study suggests a pathogenic pathway that starts with increased C-reactive protein, followed by hyponatremia and eventually ICANS and FIRDA. More studies are required to confirm our results., Classification of Evidence: This study provides Class III evidence that FIRDA on spot EEG accurately distinguishes patients with ICANS compared with those without after CAR T-cell therapy for hematologic malignancy., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Study Question: Can early pregnancies be accurately and cost-effectively diagnosed and managed using a new medical computerized tool?, Summary Answer: Compared to the standard clinical approach, retrospective implementation of the new medical software in a gynaecological emergency unit was correlated with more accurate diagnosis and more cost-effective management., What Is Known Already: Early pregnancy complications are responsible for a large percentage of consultations, mostly in emergency units, with guidelines becoming complex and poorly known/misunderstood by practitioners., Study Design, Size, Duration: A total of 780 gynaecological emergency consultations (446 patients), recorded between November 2018 and June 2019 in a tertiary university hospital, were retrospectively encoded in a new medical computerized tool. The inclusion criteria were a positive hCG test result, ultrasonographical visualization of gestational sac, and/or embryo corresponding to a gestational age of 14 weeks or less. Diagnosis and management suggested by the new computerized tool are named eDiagnoses, while those provided by a gynaecologist member of the emergency department staff are called medDiagnoses., Participants/materials, Setting, Methods: Usability was the primary endpoint, with accuracy and cost reduction, respectively, as secondary and tertiary endpoints. Identical eDiagnoses/medDiagnoses were considered as accurate. During follow-up visits, if the updated eDiagnoses and medDiagnoses became both identical to a previously discrepant eDiagnosis or medDiagnosis, this previous eDiagnosis or medDiagnosis was also considered as correct. Four double-blinded experts reviewed persistent discrepancies, determining the accurate diagnoses. eDiagnoses/medDiagnoses accuracies were compared using McNemar's Chi square test, sensitivity, specificity, and predictive values., Main Results and the Role of Chance: Only 1 (0.1%) from 780 registered medical records lacked data for full encoding. Out of the 779 remaining consultations, 675 eDiagnoses were identical to the medDiagnoses (86.6%) and 104 were discrepant (13.4%). From these 104, 60 reached an agreement during follow-up consultations, with 59 medDiagnoses ultimately changing into the initial eDiagnoses (98%) and only one discrepant eDiagnosis turning later into the initial medDiagnosis (2%). Finally, 24 remained discrepant at all subsequent checks and 20 were not re-evaluated. Out of these 44, the majority of experts agreed on 38 eDiagnoses (86%) and 5 medDiagnoses (11%, including four twin pregnancies whose twinness was the only discrepancy). No majority was reached for one discrepant eDiagnosis/medDiagnosis (2%). In total, the accuracy of eDiagnoses was 99.1% (675 + 59 + 38 = 772 eDiagnoses out of 779), versus 87.4% (675 + 1 + 5 = 681) for medDiagnoses (P < 0.0001). Calculating all basic costs of extra consultations, extra-medications, extra-surgeries, and extra-hospitalizations induced by incorrect medDiagnoses versus eDiagnoses, the new medical computerized tool would have saved 3623.75 Euros per month. Retrospectively, the medical computerized tool was usable in almost all the recorded cases (99.9%), globally more accurate (99.1% versus 87.4%), and for all diagnoses except twinning reports, and it was more cost-effective than the standard clinical approach., Limitations, Reasons for Caution: The retrospective study design is a limitation. Some observed improvements with the medical software could derive from the encoding by a rested and/or more experienced physician who had a better ultrasound interpretation. This software cannot replace clinical and ultrasonographical skills but may improve the compliance to published guidelines., Wider Implications of the Findings: This medical computerized tool is improving. A new version considers diagnosis and management of multiple pregnancies with their specificities (potentially multiple locations, chorioamnionicity). Prospective evaluations will be required. Further developmental steps are planned, including software incorporation into ultrasound devices and integration of previously published predictive/prognostic factors (e.g. serum progesterone, corpus luteum scoring)., Study Funding/competing Interest(s): No external funding was obtained for this study. F.B. and D.G. created the new medical software., Trial Registration Number: NCT03993015., (© The Author(s) 2023. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background and Purpose: In addition to combined central and peripheral demyelination, other immune diseases could involve both the central nervous system (CNS) and peripheral nervous system (PNS)., Methods: To identify immune-mediated diseases responsible for symptomatic combined central/peripheral nervous system involvement (ICCPs), we conducted a multicentric retrospective study and assessed clinical, electrophysiological, and radiological features of patients fulfilling our ICCP criteria., Results: Thirty patients (20 males) were included and followed during a median of 79.5 months (interquartile range [IQR] = 43-145). The median age at onset was 51.5 years (IQR = 39-58). Patients were assigned to one of four groups: (i) monophasic disease with concomitant CNS/PNS involvement including anti-GQ1b syndrome (acute polyradiculoneuropathy + rhombencephalitis, n = 2), checkpoint inhibitor-related toxicities (acute polyradiculoneuropathy + encephalitis, n = 3), and anti-glial fibrillary acidic protein astrocytopathy (subacute polyradiculoneuropathy and meningoencephalomyelitis with linear gadolinium enhancements, n = 2); (ii) chronic course with concomitant CNS/PNS involvement including paraneoplastic syndromes (ganglionopathy/peripheral hyperexcitability + limbic encephalitis, n = 4); (iii) chronic course with sequential CNS/PNS involvement including POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, skin changes) syndrome (polyradiculoneuropathy + strokes, n = 2), histiocytosis (polyradiculoneuropathy + lepto-/pachymeningitis, n = 1), and systemic vasculitis (multineuropathy + CNS vasculitis/pachymeningitis, n = 2); and (iv) chronic course with concomitant or sequential CNS/PNS involvement including combined central and peripheral demyelination (polyradiculoneuropathy + CNS demyelinating lesions, n = 10) and connective tissue diseases (ganglionopathy/radiculopathy/multineuropathy + limbic encephalitis/transverse myelitis/stroke, n = 4)., Conclusions: We diagnosed nine ICCPs. The timing of central and peripheral manifestations and the disease course help determine the underlying immune disease. When antibody against neuroglial antigen is identified, CNS and PNS involvement is systematically concomitant, suggesting a common CNS/PNS antigen and a simultaneous disruption of blood-nerve and blood-brain barriers., (© 2022 European Academy of Neurology.)

Objective: To analyze quality of life(QoL) and symptom resolution after surgical removal of Essure devices., Methods: Single-center cohort study which included patients with Essure removal between February 2017 and March 2018. Surgery was performed in 65 patients by laparoscopy (Salpingectomy only or Hysterectomy). Questionnaires were used to assess QoL(SF-36), emotional disorders(HAD) and symptoms preoperatively, at 3 months and 4 years postoperatively., Results: 4(6,1%) and 16(24,6%) patients were lost of follow-up at three months and 4 years postoperatively respectively. Four(6,1%) intraoperative surgical complications occurred. During the three-months postoperative period, 3(4,6%) complications occurred: five Clavien Dindo Grade 1 complications (umbilical hematoma) and one Grade 2 complication (hyperthermia and digestive disorder requiring antibiotic therapy). Preoperative QoL scores were lower than those of general population. Scores were significantly improved at 3 months and 4 years postoperatively. At 4 years postoperatively, 17/49(34,7%) had a complete regression of symptoms, 21/49(42,8%) partial resolution and 11/49(22,4%) no improvement. 27/49(55,1%) patients made the connection between symptoms and ESSURE device after media coverage. 22/49(44,89 %) were influenced by media coverage in their decision of surgery. There was a higher percentage of patients with anxiety disorder before Essure removal than 4 years after [22/44 (50 %) versus 11/44 (25 %); p = 0.0045]., Conclusion: Essure removal has a restorative role in terms of QoL in short and long-term. Patients should be informed about possibility of no improvement after surgery and surgical morbidity. Larger prospective cohort is needed to make a well-considered decision about risks of surgery compared with expected benefits., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: The relationship between the driving pressure of the respiratory system (ΔPrs) under mechanical ventilation and worse outcome has never been studied specifically in chest trauma patients. The objective of the present study was to assess in cases of chest trauma the relationship between ΔPrs and severity of acute respiratory distress syndrome (ARDS) or death and length of stay., Methods: A retrospective analysis of severe trauma patients (ISS > 15) with chest injuries admitted to the Trauma Centre from January 2010 to December 2018 was performed. Patients who received mechanical ventilation were included in our analysis. Mechanical ventilation parameters and ΔPrs were recorded during the stay in the intensive care unit. Association of ΔPrs with mortality and outcomes was specifically studied at the onset of ARDS (ΔPrs -ARDS ) by receiver operator characteristic curve analysis, Kaplan-Meier curves, and multivariate analysis., Results: Among the 266 chest trauma patients studied, 194 (73%) developed ARDS. ΔPrs was significantly higher in the ARDS group versus in the no ARDS group (11.6 ± 2.4 cm H 2 O vs. 10.9 ± 1.9 cm H 2 O, p = 0.04). Among the patients with ARDS, no difference according to the duration of mechanical ventilation was found between the high ΔPrs group (ΔPrs -ARDS > 14 cm H 2 O) and the low ΔPrs group (ΔPrs -ARDS ≤ 14 cm H 2 O), (p = 0.75). ΔPrs -ARDS was not independently associated with the duration of mechanical ventilation (hazard ratio [HR], 1.006; 95% CI, 0.95-1.07; p = 0.8) or mortality (HR, 1.07; 95% CI, 0.9-1.28; p = 0.45). High mechanical power (≥ 12 J/min) was associated with a lower time for weaning of mechanical ventilation in Kaplan-Meier curves but not in multivariate analysis (HR, 0.98; 95% CI, 0.94-1.02; p = 0.22)., Conclusion: A high ΔPrs -ARDS was not significantly associated with an increase in mechanical ventilation duration or mortality risk in ARDS patients with chest trauma in contrast with medical patients., (Copyright © 2022 Société française d'anesthésie et de réanimation (Sfar). Published by Elsevier Masson SAS. All rights reserved.)

Background: Approximately 7% of breast cancers are diagnosed in women under 40. Question of subsequent fertility has become fundamental. We aimed to evaluate the rate of fertility preservation (FP) by oocyte retrieval (OR) after ovarian stimulation in patients of childbearing age, managed for breast cancer with adjuvant chemotherapy in France, reuse rate of frozen gametes and live births rate (LBR) after treatment., Methods: We included 15,774 women between 18 and 40 years old, managed by surgery and adjuvant chemotherapy for breast cancer, between January 2011 and December 2020 from a French health registry. Patients with OR after breast surgery and before chemotherapy were considered as FP group; those with no OR as no FP group. To compare LBR with French population independently of age, we calculated Standardized Incidence Rates (SIR) of live births using indirect standardization method., Results: FP rate increased gradually since 2011, reaching 17% in 2019. A decrease in use was observed in 2020 (13,9%). Among patients with at least 2 years of follow-up, gamete reuse rate was 5,6%. Births after cancer were mostly from spontaneous pregnancies. Among patients with at least 3 years of follow-up, LBR was 19,6% in FP group, 3,9% in second group. SIR of live births was of 1,05 (95% CI = 0.91-1.19) and 0.33 (95% CI = 0.30-0.36) in FP and no FP group respectively., Conclusion: Oncofertility activity increased until 2019 in France, reaching 17%. Gamete reuse rate was low. Births resulted mainly from spontaneous pregnancies. SIR of live births was lower in no FP group., (Copyright © 2022. Published by Elsevier Ltd.)

Aims: Virtual reality hypnosis (VRH) has been used successfully in various clinical settings to decrease anxiety and the sensation of pain. We aimed to investigate the feasibility and safety of VRH in patients undergoing electrophysiology and pacing procedures under conscious sedation. Methods: During a two-month period, VRH support was proposed and accepted by 25 patients undergoing electrophysiological procedures. Data were compared with a control group (n = 61) enrolled during the following three-month period. Both groups underwent the measurement of the duration of intervention, the consumption of analgesics and hypnotics, and their pain and comfort using a validated visual analogue scale (VAS 0−10). Results: The baseline characteristics were comparable in both groups, including age. There were no differences in procedure duration (46 (±29) vs. 56 (±32) min, p = 0.18) or in hypnotic/antalgic consumption (midazolam 1.95 (±1.44) vs. 2.00 (±1.22) mg, p = 0.83; sufentanyl 3.78 (±2.87) vs. 3.58 (±2.48) μg, p = 0.9) between the control and VRH groups. In a multivariate analysis, the use of VRH was independently associated with lower comfort during the procedure assessed by postoperative visual analogue scale (OR 15.00 [95% CI 4.77−47.16], p < 0.01). There was no influence of VRH use on pain or drug consumption. Conclusions: In our experience, compared with VRH, human care is preferable during procedures in electrophysiology lab to improve the comfort of the patient. VRH has no influence on pain or drug consumption.

Increasing number of medical students and limited availability of cadavers have led to a reduction in anatomy teaching through human cadaveric dissection. These changes triggered the emergence of innovative teaching and learning strategies in order to maximize students learning of anatomy. An alternative approach to traditional dissection was presented in an effort to improve content delivery and student satisfaction. The objective of this study is to acquire three-dimensional (3D) anatomical data using structured-light surface scanning to create a dynamic four-dimensional (4D) dissection tool of four regions: neck, male inguinal and femoral areas, female perineum, and brachial plexus. At each dissection step, identified anatomical structures were scanned using a 3D surface scanner (Artec Spider™). Resulting 3D color meshes were overlaid to create a 4D (3D+time) environment. An educational interface was created for neck dissection. Its implementation in the visualization platform allowed 4D virtual dissection by navigating from surface to deep layers and vice versa. A group of 28 second-year medical students and 17 first-year surgery residents completed a satisfaction survey. A majority of medical students (96.4%) and 100% of surgery residents said that they would recommend this tool to their colleagues. According to surgery residents, the main elements of this virtual tool were the realistic high-quality of 3D acquisitions and possibility to focus on each anatomical structure. As for medical students, major elements were the interactivity and entertainment aspect, precision, and accuracy of anatomical structures. This approach proves that innovative solutions to anatomy education can be found to help to maintain critical content and student satisfaction in anatomy curriculum., (© 2021 American Association for Anatomy.)

Objectives: To describe the initial care practices for children with Pierre Robin sequence (PRS) and analyze the factors predicting the severity of the obstruction breathing disorders., Design: A retrospective single-center study of 150 children with PRS., Setting: Single tertiary care center, Regional Competence Center for the diagnosis and treatment of PRS., Patients: A total of 150 children with PRS consecutively followed between 1986 and 2017. Group 1 comprises children without specific respiratory management; group 2, children requiring prone positioning to alleviate their respiratory distress symptoms; and group 3, children requiring nasopharyngeal airway tube (NT) or nonconservative surgical treatment., Main Outcome Measures: Evolution and results of the initial treatment of PRS., Results: Forty-two percent (n = 63) were attributed to group 1, 39% (n = 50) to group 2, and 19% (n = 29) to group 3. Preterm birth, birth weight, or associated congenital malformations were not significantly different between the groups. However, the age of exclusive oral feeding was significantly different: 1 day (quartiles: 0-3) for group 1; 11 days (quartiles: 1-28) for group 2; 39 days (quartiles: 19-111) for group 3 ( P < .0001). Considering the NT, its use relieves the upper airway obstruction, assessed by a respiratory polygraphy, in 14 children., Conclusions: Nasopharyngeal airway tube has become our major first-line treatment, avoiding more complex procedures in most of the cases. The achievement of exclusive oral feeding seems to be a good predictor of the severity of respiratory symptoms in PRS.

Background and Purpose: The best transportation strategy for patients with suspected large vessel occlusion (LVO) is unknown. Here, we evaluated a new regional strategy of direct transportation to a Comprehensive Stroke Center (CSC) for patients with suspected LVO and low probability of receiving intravenous thrombolysis (IVT) at the nearest Primary Stroke Center (PSC)., Methods: Patients could be directly transported to the CSC (bypass group) if they met our pre-hospital bypass criteria: high LVO probability (i.e., severe hemiplegia) with low IVT probability (contraindications) and/or travel time difference between CSC and PSC<15 minutes. The other patients were transported to the PSC according to a "drip-and-ship" strategy. Treatment time metrics were compared in patients with pre-hospital bypass criteria and confirmed LVO in the bypass and drip-and-ship groups., Results: In the bypass group (n=79), 54/79 (68.3%) patients met the bypass criteria and 29 (36.7%) had confirmed LVO. The positive predictive value of the hemiplegia criterion for LVO detection was 0.49. In the drip-and-ship group (n=457), 92/457 (20.1%) patients with confirmed LVO met our bypass criteria. Among the 121 patients with bypass criteria and confirmed LVO, direct routing decreased the time between symptom discovery and groin puncture by 55 minutes compared with the drip-and-ship strategy (325 vs. 229 minutes, P<0.001), without significantly increasing the time to IVT (P=0.19)., Conclusions: Our regional strategy led to the correct identification of LVO and a significant decrease of the time to mechanical thrombectomy, without increasing the time to IVT, and could be easily implemented in other territories., (Copyright © 2021 Elsevier Masson SAS. All rights reserved.)

Aim: The link between social deprivation and the development of diabetic foot ulcer (DFU) is still widely debated. The study objective was to evaluate the relationship between lower limb amputation, social deprivation level, and inequalities in access to care service among people with DFU. This regional pilot study was conducted at the living area level and based on the French National Health Data System (SNDS)., Methods: We conducted a retrospective cohort study using hospital and primary care claim data in the Languedoc-Roussillon region. DFUs were determined using an original algorithm of care consumption or hospital diagnosis. The primary end point was amputation at 1 year. Secondary end points were mortality at 1 year and impact of potential access to care on amputation., Results: We included 15,507 people from 2015 to 2017. Amputation and mortality rates were 17.5 and 117 per 1000 person-years. The least precarious living areas showed better prognoses (relative risk = 0.46; 95% CI 0.27-0.66). Territorial accessibility to a private-practice nurse, unlike physician accessibility, was associated with better results on major outcomes (p = 0.004)., Conclusion: This is the first study using SNDS to study the care pathway of DFU management within and outside the hospital. High social deprivation in a living areas seems to be associated with more major amputations after a DFU., (© 2022 Diabetes UK.)

Kabuki syndrome (KS) is a rare genetic disorder caused by mutations in two major genes, KMT2D and KDM6A, that are responsible for Kabuki syndrome 1 (KS1, OMIM147920) and Kabuki syndrome 2 (KS2, OMIM300867), respectively. We lack a description of clinical signs to distinguish KS1 and KS2. We used facial morphology analysis to detect any facial morphological differences between the two KS types. We used a facial-recognition algorithm to explore any facial morphologic differences between the two types of KS. We compared several image series of KS1 and KS2 individuals, then compared images of those of Caucasian origin only (12 individuals for each gene) because this was the main ethnicity in this series. We also collected 32 images from the literature to amass a large series. We externally validated results obtained by the algorithm with evaluations by trained clinical geneticists using the same set of pictures. Use of the algorithm revealed a statistically significant difference between each group for our series of images, demonstrating a different facial morphotype between KS1 and KS2 individuals (mean area under the receiver operating characteristic curve = 0.85 [p = 0.027] between KS1 and KS2). The algorithm was better at discriminating between the two types of KS with images from our series than those from the literature (p = 0.0007). Clinical geneticists trained to distinguished KS1 and KS2 significantly recognised a unique facial morphotype, which validated algorithm findings (p = 1.6e-11). Our deep-neural-network-driven facial-recognition algorithm can reveal specific composite gestalt images for KS1 and KS2 individuals., (© 2021. The Author(s), under exclusive licence to European Society of Human Genetics.)

Background: To evaluate the efficacy for symptomatic knee and hip osteoarthritis (OA) patients of a mindfulness-based stress reduction (MBSR) program versus usual care., Methods: Randomized, physician-blind, clinical trial in a monocentric prospective pilot study. Adult participants with symptomatic knee or hip OA were randomized into either intervention or control groups. The intervention group completed the MBSR program for a two-and-a-half-hour weekly session for 8 weeks. Usual care management was similar in both groups. All patients were evaluated at baseline, 3 months and 6 months. The primary objective was to evaluate the change in WOMAC pain score between baseline and 3 months in the MBSR group compared to usual care group. Secondary objectives were to evaluate changes in pain VAS, WOMAC scores, quality of life (SF-36), HAD scores between baseline and 3/6 months., Results: Forty patients were enrolled in the study. No differences in the WOMAC pain score between the two groups were observed in the different time points. A similar pattern was found for the other assessment outcomes. However, a significant pain VAS reduction in favor of the MBSR group between baseline and 6 months (- 29.6 ± 26.6 vs - 9.3 ± 27.3; p = 0.03) has been reached., Conclusions: Our pilot RCT found contrasting results with no benefit on WOMAC pain and function and a delayed but long-term efficacy in pain VAS following a MBSR program in symptomatic knee or hip OA patients. Future studies with larger sample size are mandatory to confirm these preliminary results. Trial registration The study was registered in ClinicalTrials.gov (NCT03644615, 23/08/2018)., (© 2022. The Author(s).)

Background: Right ventricular (RV) dysfunction and tricuspid regurgitation (TR) may impact prognosis of patients undergoing Transcatheter Aortic Valve Implantation (TAVI). We aimed to evaluate the evolution of previous RV dysfunction and/or significant TR after TAVI procedure., Methods: All patients undergoing TAVI between January 2018 and January 2019 were enrolled in this prospective cohort. Patients with at least one right heart (RH) abnormality at baseline including RV dysfunction (TAPSE < 17 mm, S-wave < 9.5 cm/s, Fractional area change < 35%, Strain > -20%, Tei > 0.54) and/or significant TR (Effective Regurgitant Orifice Area ≥ 40 mm2 and/or Regurgitant Volume ≥ 45 mL) underwent transthoracic echocardiography at day 1 and 6-month after TAVI. The primary endpoint was the regression of pre-TAVI RV dysfunction and/or significant TR at 6-month follow-up., Results: The study enrolled 144 patients including 76 women (52.8%) with a mean age of 81.1 ± 6.8 yo, a mean EuroSCORE 2 of 5.2 ± 3.9%. At least one RH abnormality was observed in 53 patients (36.8%). At 6-month, at least one RV dysfunction parameter significantly improved in 26 patients (63.4%), TAPSE increasing from 13.0 ± 2.6 to 16.0 ± 9.8 mm, p < 0.0001 and S-wave from 7.7 ± 1.2 to 10.0 ± 2.6 cm/s, p = 0.004. Among 31 patients with baseline significant TR, TR decreased in 14 (45.2%); p = 0.003. Among patients with baseline RH abnormalities, 13 (24.5%) fully recovered. Baseline significant TR was predictive of 6-month clinical outcomes (OR = 3.1, 95%CI = [1.01-9.0], p = 0.03)., Conclusion: In our recent intermediate surgical risk TAVI population, RV dysfunction and/or significant TR are frequent at baseline and fully or partially recover in most patients at 6-month follow-up., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: A detailed quantitative evaluation would be beneficial for management of patients with limb lymphedema. Methods and Results: In 47 patients with lower limb lymphedema at International Society of Lymphology clinical stage 2A (18 limbs), 2B (41 limbs), and 3 (13 limbs), we measured the limb circumference and thickness of epidermis, dermis, and subcutis layers with B-mode ultrasonography and subcutis elastic modulus with ultrafast shear wave velocity (ultrasound elastography) at 5 anatomical levels (M1 to M5) before and after a 3- to 5-day intensive decongestive therapy (IDT) session. Limb circumference and thickness of the epidermis, dermis, and subcutis were greater in the 72 limbs with lymphedema than in the 22 unaffected limbs before and after IDT. The affected limb volume was 10,980 [8458-13,960] mL before and 9607 [7720-11,830] mL after IDT ( p  < 0.0001). The IDT-induced change in subcutis thickness was -9 [-25 to 13]% (NS), -11 [-26 to 3]% ( p  = 0.001), -18 [-40 to -1]% ( p  < 0.0001), -15 [-35 to 3]% ( p  = 0.0003), and -25 [-45 to -4]% ( p  < 0.0001) and significantly correlated with the change in elastic modulus, which was 13 [-21 to 90]% ( p  = 0.004), 33 [-27 to 115]% ( p  = 0.0002), 40[-13 to 169]% ( p  < 0.0001), 9 [-36 to 157]% ( p  = 0.024), and -13 [-40 to 97]% (NS), respectively, at the M1, M2, M3, M4, and M5 levels. Intraobserver reproducibility was satisfactory for skin thickness and fairly good for elastography, but interobserver reproducibility was poor or unacceptable. Conclusions: IDT reduced the circumference and subcutis thickness of lower limbs with lymphedema and increased their elastic modulus, implying greater tissue stiffness probably due to fluid evacuation. Although subcutis thickness measurement proved to be reliable, technological and methodological improvements are required before ultrasonographic elastography can be used in clinical practice.

Background: In a recent Italian study, 30% of patients with reversible cerebral vasoconstriction syndrome (RCVS) presented without thunderclap headache (TCH), and tended to present more severe forms of RCVS than patients with TCH. We aimed to analyze the risk for complications of RCVS in patients with and without TCH at onset., Methods: In a pooled cohort of 345 French patients with RCVS, we compared patients with and without TCH at onset regarding rates of neurological complications, and the functional outcome at 3 months., Results: As compared to the 281 patients with TCH at onset, the 64 patients without TCH had a higher risk for any neurological complication (61% vs. 24%, OR 4.9, 95% CI 2.8-8.7, p < 0.001). The association was strongest for cervical artery dissections (28% vs. 5%, OR 8.1, 95% CI 3.7-17.6, p < 0.001), followed by posterior reversible encephalopathy syndrome (17% vs. 3%, OR 7.1, 95% CI 2.7-18.4, p < 0.001), seizures (9% vs. 2.5%, OR 4.1, 95% CI 1.3-12.5, p = 0.019), and subarachnoid hemorrhage (41% vs. 16%, OR 3.5, 95% CI 1.9-6.3, p < 0.001). In multivariable analysis, the risk for any neurological complication remained significantly elevated in the absence of TCH (OR 3.5, 95% CI 1.8-6.8, p < 0.001). The functional outcome was equal in both groups, with a modified Rankin scale score of 0-1 in ≥90% of patients., Conclusions: Absence of TCH at onset might predict a higher risk of complications in RCVS. Our results warrant further multicentric studies to prove this finding., (© 2021 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Objectives: This study aimed to investigate a potential daily-life concern for patients with diabetes hypoglycemia while driving by (1) estimating their incidence in insulin-treated drivers, (2) determining factors associated with their occurrence, and (3) analyzing patients' behavior regarding prevention of hypoglycemia., Methods: We conducted an observational study from November 2013 to May 2018 in the endocrinology-diabetology-nutrition department of our university hospital. All patients treated for diabetes older than 18 years admitted in the department were eligible. A specific questionnaire assessing attitudes, knowledge, and consequences of hypoglycemia was provided. In this study, only insulin-treated patients who regularly drive were analyzed., Results: On the 233 insulin-treated drivers included, 45 (19%) self-reported at least 1 hypoglycemia while driving in the preceding year. Two factors were significantly associated with their occurrence: type 1 diabetes (odds ratio [OR] = 3.19; 95% confidence interval [CI] = 1.55-6.57) and experiences of asymptomatic hypoglycemia (OR = 2.20; 95% CI = 1.05-4.63). Awareness of the treatment hypoglycemia risk because of information provided by a medical specialist was also but nonsignificantly associated with hypoglycemia while driving (OR = 2.61; 95% CI = 0.86-7.92). Forty-one patients (18%) combined those 3 variables, 20 (49%) of them self-reported hypoglycemia while driving. Thirty-four percent of the patients never carried carbohydrates for hypoglycemia correction. Seventy-six percent do not monitor blood glucose level before driving., Conclusions: Our questionnaire allowed us to highlight that 19% our cohort of insulin-treated drivers declared experiencing hypoglycemia while driving. Risk factors identified and prevention data collected should help us better target patient education., Competing Interests: The authors disclose no conflict of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Background: After a stroke, 80% of the chronic patients have difficulties to use their paretic upper limb (UL) in activities of daily life (ADL) even after rehabilitation. Virtual reality therapy (VRT) and anodal transcranial direct current stimulation (tDCS) are two innovative methods that have shown independently to positively impact functional recovery of the paretic UL when combined with conventional therapy. The objective of the project will be to evaluate the impact of adding anodal high-definition (HD)-tDCS during an intensive 3-week UL VRT and conventional therapy program on paretic UL function in chronic stroke., Methods: The ReArm project is a quadruple-blinded, randomized, sham-controlled, bi-centre, two-arm parallel, and interventional study design. Fifty-eight chronic (> 3 months) stroke patients will be recruited from the Montpellier and Nimes University Hospitals. Patients will follow a standard 3-week in-patient rehabilitation program, which includes 13 days of VRT (Armeo Spring, 1 × 30 min session/day) and conventional therapy (3 × 30 min sessions/day). Twenty-nine patients will receive real stimulation (4x1 anodal HD-tDCS montage, 2 mA, 20 min) to the ipsilesional primary motor cortex during the VRT session and the other 29 patients will receive active sham stimulation (2 mA, 30 s). All outcome measures will be assessed at baseline, at the end of rehabilitation and again 3 months later. The primary outcome measure will be the wolf motor function test. Secondary outcomes will include measures of UL function (Box and Block Test), impairment (Fugl Meyer Upper Extremity), compensation (Proximal Arm Non-Use), ADL (Actimetry, Barthel Index). Other/exploratory outcomes will include pain, fatigue, effort and performance, kinematics, and motor cortical region activation during functional motor tasks., Discussion: This will be the first trial to determine the impact of adding HD-tDCS during UL VRT and conventional therapy in chronic stroke patients. We hypothesize that improvements in UL function will be greater and longer-lasting with real stimulation than in those receiving sham., Trial Registration: The ReArm project was approved by The French Research Ethics Committee, (Comité de Protection des Personnes-CPP SUD-EST II, N°ID-RCB: 2019-A00506-51, http://www.cppsudest2.fr/ ). The ReArm project was registered on ClinicalTrials.gov ( NCT04291573 , 2 nd March 2020., (© 2021. The Author(s).)

Introduction: Tubulointerstitial nephritis (TIN) and uveitis (TINU) syndrome is a rare disease. The renal prognosis is generally thought to be better in children with TINU syndrome than in adults. However, data are scarce. We aimed to investigate the long-term renal prognosis in a French cohort of children with TINU syndrome., Methods: We performed a national retrospective study including 23 French pediatric nephrology centers enrolling patients with TINU syndrome diagnosed between January 2000 and December 2018., Results: A total of 46 patients were included (52% female, median age 13.8 years). At diagnosis of TIN, the median estimated glomerular filtration rate (eGFR) was 30.6 ml/min per 1.73 m 2 (4.9-62.8). The median time between diagnosis of uveitis and TIN was 0.4 months (-4.1; +17.1). All patients had anterior uveitis, but 12 (29%) were asymptomatic. Nearly all patients (44 of 46) received steroid treatment, and 12 patients (26%) received a second-line therapy. At last follow-up (median 2.8 years), the median eGFR was 87.5 ml/min per 1.73 m 2 (60.3-152.7) and <90 ml/min per 1.73 m 2 in 20 patients., Conclusion: In our study, nearly half of the patients had renal sequelae at last follow-up. Given the possible progression to chronic kidney disease, long-term monitoring of children with TINU syndrome is mandatory. Approximately a quarter of the children had asymptomatic uveitis suggesting all children presenting with TIN should undergo systematic ophthalmologic screening even in the absence of ocular signs., (© 2021 International Society of Nephrology. Published by Elsevier Inc.)

Forensic dentistry is the branch of forensic science concerned with the study of teeth and jaws. To facilitate the work of experts, new comparative identification tools are emerging, with digital techniques such as the intra-oral camera, which are revolutionising current techniques in forensic dentistry., Objective: The aim of this study is to evaluate the diagnostic quality of the post-mortem odontogram carried out remotely via a video of the oral cavity using an intra-oral camera. The gold standard is the post-mortem odontogram obtained via the standard identification technique during the clinical examination., Materials and Methods: 25 deceased patients were included in the study and the data were collected in the Forensic Medicine and Thanatology Department at the University Hospital of Montpellier. The protocol was divided into three stages: the gold standard consultation, the recording of videos with the Soprocare® camera, and the remote analysis of the images obtained. The gold standard consultation and the remote analysis were carried out by two separate dental surgeons responsible for completing a clinical file, used to establish the odontogram of the deceased patient., Results: The study was carried out on 25 deceased subjects, between 13 May and 12 June 2019. Our sample was composed of 68% men and 32% women. A sensitivity threshold of 0.97 was observed for the performance of the odontogram, i.e., for all the teeth actually present in the mouth for all subjects in the study, 97% of them were identified with the videos taken using the intraoral camera. The examination with the intra-oral camera demonstrated a good diagnostic performance in the detection of missing teeth with a PPV of 97.9% and a NPV of 98.2%. Practitioner became more skilled at recording the videos with the intra-oral camera. One can therefore note an ease in the handling of this digital tool, which gradually improved with the number of subjects included in the study CONCLUSIONS: The Soprocare® intraoral camera has an acceptable diagnostic validity in establishing the odontogram of the deceased. It enables fundamental elements to be detected with optimal efficiency. However, several points still need to be improved, in order to make the use of the camera during data collection as easy and efficient as possible., Competing Interests: Conflict of interest Authors declare no conflict of interest., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Background and Purpose: Previous studies have demonstrated the usefulness of non-EPI DWI for detection of residual cholesteatoma. However, limited data are available to determine the suitable duration of imaging follow-up after a first MR imaging with normal findings has been obtained. The present study aimed to determine the optimal duration of non-EPI DWI follow-up for residual cholesteatoma., Materials and Methods: A retrospective, monocentric study was performed between 2013 and 2019 and included all participants followed up after canal wall up tympanoplasty with at least 2 non-EPI DWI examinations performed on the same 1.5T MR imaging scanner. MR images were reviewed independently by 2 radiologists. Sensitivity and specificity values were calculated as a function of time after the operation. Receiver operating characteristic curves were analyzed to determine the optimal follow-up duration., Results: We analyzed 47 MRIs from 17 participants. At the end of the individual follow-up period, a residual cholesteatoma had been found in 41.1% of cases. The follow-up duration ranged from 20 to 198 months (mean, 65.9 [SD, 43.9] months). Participants underwent between 2 and 5 non-EPI DWI examinations. Analyses of the receiver operating characteristic curves revealed that the optimal diagnostic value of non-EPI DWI occurred 56 months after the operation when the first MR imaging performed a mean of 17.3 (SD, 6.8) months after the operation had normal findings (sensitivity = 0.71; specificity = 0.7, Youden index = 0.43)., Conclusions: Repeat non-EPI DWI is required to detect slow-growing middle ear residual cholesteatomas. We, therefore, recommend performing non-EPI DWI for at least the first 5 years after the initial operation., (© 2021 by American Journal of Neuroradiology.)

Despite improvement in the prognosis of ANCA-associated vasculitides (AAVs), increased mortality, mainly from a cardiovascular origin, persists. We aimed to determine the role of cardiovascular risk factors (CVRFs) on the occurrence of major cardiovascular events (MACEs) in AAVs. Patients with AAVs were successively included in a prospective cohort study, which assessed CVRFs (defined by age >50 years in men and >60 years in women, personal history of cardiovascular disease, smoking status, obesity, diabetes, dyslipidemia, hypertension, and sedentary lifestyle), the use of glucocorticoids and immunosuppressive agents at baseline and during follow-up, and the occurrence of MACEs. One hundred and three patients were included, with a median follow-up time of 3.5 years. In the glucocorticoids and cyclophosphamide adjusted multivariate analysis, the occurrence of MACEs was associated with older age ( p = 0.001, OR = 14.71, 95% CI (confidence interval) = 2.98-72.68), cardiovascular history ( p = 0.007, OR (odds ratio) = 6.54, 95% CI = 1.66-25.71), sedentary lifestyle ( p = 0.011, OR = 4.50, 95% CI = 1.42-14.29), hypertension ( p = 0.017, OR = 5.04, 95% CI = 1.33-19.12), and dyslipidemia ( p = 0.03, OR = 3.86, 95% CI = 1.14-13.09). The occurrence of MACEs was associated with the number of CVRFs ( p < 0.001), but not with the use of glucocorticoids or cyclophosphamide ( p = 0.733 and p = 0.339, respectively). The implementation of a screening and management program for modifiable CVRFs, particularly hypertension, sedentary lifestyle, and dyslipidemia, may be beneficial for AAV patients in order to reduce their cardiovascular risk.

Aims: Transition care programmes are designed to improve coordination of care between hospital and home. For heart failure patients, meta-analyses show a high efficacy but with moderate evidence level. Moreover, difficulties for implementation of such programmes limit their extrapolation., Methods and Results: We designed a mixed-method study to assess the implementation of the PRADO-IC, a nationwide transition programme that aims to be offered to every patient with heart failure in France. This programme consists essentially in an administrative assistance to schedule follow-up visits and in a nurse follow-up during 2 to 6 months and aims to reduce the annual heart failure readmission rate by 30%. This study assessed three quantitative aims: the cost to avoid a readmission for heart failure within 1 year (primary aim, intended sample size 404 patients), clinical care pathways, and system economic outcomes; and two qualitative aims: perceived problems and benefits of the PRADO-IC. All analyses will be gathered at the end of study for a joint interpretation. Strengths of this study design are the randomized controlled design, the population included in six centres with low motivation bias, the primary efficiency analysis, the secondary efficacy analyses on care pathway and clinical outcomes, and the joint qualitative analysis. Limits are the heterogeneity of centres and of intervention in a control group and parallel development of other new therapeutic interventions in this field., Conclusions: The results of this study may help decision-makers to support an administratively managed transition programme., (© 2020 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Background: Whether soluble urokinase-type plasminogen activator receptor (suPAR) could be a valuable prognostic indicator remains uncertain., Materials & Methods: Patients from STADE-HF (Soluble Suppression of Tumorigenesis-2 as a Help for Management of Diagnosis, Evaluation and Management of Heart Failure) were included for analysis., Results: 95 patients were included. The suPAR level of expression was significantly higher in the group of patients who died at one month (7.90 ± 4.35 ng/ml vs 11.94 ± 6.86 ng/ml; p < 0.05) or 1 year (7.28 ± 4.27 ng/ml vs 11.81 ± 4.88 ng/ml; p < 0.01), but there was no significant difference according to the readmission., Conclusion: High suPAR levels during hospitalization for acute heart failure were highly predictive for the risk of mortality, but not the risk of readmission., Competing Interests: Financial & competing interests disclosure The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties. No writing assistance was utilized in the production of this manuscript., (© 2021 Fabien Huet.)

A simple and accurate prognostic tool for Heart Failure (HF) patients is critical to improve follow-up. Different risk scores are accurate but with limited clinical applicability. The current study aims to derive and validate a simple predictive tool for HF prognosis. French outpatients with stable HF of two university hospitals were included in the derivation (N = 134) or in the validation (N = 274) sample and followed up for a median of 23 months. Potential predictors were variables with known association with mortality and easily available. The proSCANNED risk score was derived using a parametric survival model on complete case data; it includes 8 binary variables and its values are 0-8. In the validation sample, the ability of the score to discriminate the 1-year vital status was moderate (AUC = 0.71, IC95% = [0.64-0.71]). However, the stratification of the score in three groups showed a good calibration for patients in the low- and medium-risk risk group. The proSCANNED score is an easy-to-use tool in clinical practice with a good discrimination, stability, and calibration sufficient to improve the medical care of patients. Other follow up studies are necessary to assess score applicability in larger populations, and its impact.

Objective: To determine whether adult cases of Chronic Lymphocytic Inflammation with Pontine Perivascular Enhancement Responsive to Steroids (CLIPPERS) may be related to familial hemophagocytic lymphohistiocytosis (HLH) causes, we have screened patients with adult-onset CLIPPERS for mutations in primary HLH-associated genes., Methods: In our cohort of 36 patients fulfilling the criteria for probable or definite CLIPPERS according to the CLIPPERS-2017 criteria, we conducted a first study on 12 patients who consented to genetic testing. In these 12 patients, systemic HLH criteria were searched, and genetic analysis of 8 genes involved in primary HLH was performed., Results: Four definite and 8 probable CLIPPERS were enrolled (n = 12). Mutations involved in HLH were identified in 2 definite and 2 probable CLIPPERS (4/12). Three of them had biallelic PRF1 mutations with reduced perforin expression in natural killer cells. The remaining patient had biallelic UNC13D mutations with cytotoxic lymphocyte impaired degranulation. None of the mutated patients reached the criteria for systemic HLH. During follow-up, 3 of them displayed atypical findings for CLIPPERS, including emergence of systemic non-Hodgkin lymphoma (1/3) and confluent gadolinium-enhancing lesions on brain MRI (3/3)., Conclusions: In our patients presenting with adult-onset CLIPPERS, one-third have HLH gene mutations. This genetic treatable condition should be searched in patients with CLIPPERS, especially in those presenting with atypical findings., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Context: Primary Sjögren's syndrome (pSS) is a complex heterogeneous autoimmune disease (AID) which can mimic rheumatoid arthritis (RA) or systemic lupus erythematosus (SLE). Our exploratory study investigated serum biomarkers that may discriminate pSS from RA and SLE., Methods: Serum concentrations of 63 biomarkers involved in immune cell trafficking, inflammatory response, cellular movement, and cell-to-cell signaling were measured in AID patients, included prospectively into the study at the Montpellier University Hospital. A multivariate analysis by multiple logistic regression was performed, and discriminative power assessed using logistic regression adjusted on significant demographic factors., Results: Among the 95 patients enrolled, 42 suffered from pSS, 28 from RA, and 25 from SLE. Statistical analysis showed that concentrations of BDNF (OR = 0.493 with 95% CI [0.273-0.891]; p = 0.0193) and I-TAC/CXCL11 (OR = 1.344 with 95% CI [1.027-1.76]; p = 0.0314) can significantly discriminate pSS from RA. Similarly, greater concentrations of sCD163 (OR = 0.803 with 95% CI [0.649-0.994]; p = 0.0436), Fractalkine/CX3CL1 (OR = 0.534 with 95% CI [0.287-0. 991]; p = 0.0466), MCP-1/CCL2 (OR = 0.839 with 95% CI [0.732-0.962]; p = 0.0121), and TNFa (OR = 0.479 with 95% CI [0.247-0.928]; p = 0.0292) were associated with SLE diagnosis compared to pSS. In addition, the combination of low concentrations of BDNF and Fractalkine/CX3CL1 was highly specific for pSS (specificity 96.2%; positive predictive value 80%) compared to RA and SLE, as well as the combination of high concentrations of I-TAC/CXCL11 and low concentrations of sCD163 (specificity 98.1%; positive predictive value 75%)., Conclusion: Our study highlights biomarkers potentially involved in pSS, RA, and SLE pathophysiology that could be useful for developing a pSS-specific diagnostic tool., Competing Interests: PGa was employed by company BioRad. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Padern, Duflos, Ferreira, Assou, Guilpain, Maria, Goulabchand, Galea, Jurtela, Jorgensen and Pers.)

Introduction: Increasing reports of adverse effects have raised concerns about the Essure hysteroscopic sterilization method. Women suffering alleged complications of the Essure device often seek surgical removal. This study evaluated the quality of life (QoL) and postoperative outcomes in women undergoing Essure removal., Material and Methods: This observational case series included 95 women. Removal was performed by laparoscopic salpingectomy-cornuectomy, or hysterectomy with bilateral salpingectomy. QoL was assessed preoperatively and three months postoperatively by SF-36 questionnaires [correlated physical health score (PCS) and mental health scores (MCS)]. Symptoms evolution was collected at three months, and complications at one month., Results: Sixty-four laparoscopic salpingectomy-cornuectomies, 33 laparoscopic hysterectomies, and eight vaginal hysterectomies were performed. Four intraoperative complications occurred (one conversion from cornuectomy to laparoscopic hysterectomy, one skin burn, two bladder injuries). Seven postoperative complications occurred (Clavien Dindo, grade 1 or 2). All components of the preoperative QoL scores were lower than those of the general population. PCS scores were lower preoperatively than postoperatively [37.6 versus 50.7; p<0.001]. MCS scores were lower preoperatively than postoperatively [29 versus 52.4; p<0.001]. 71% of patients showed an improvement of at least 10% in both PCS and MCS scores. Systemic and gynecologic symptoms were more frequent before than after surgery (98% versus 50%; p<0.001 and 77% versus 20%; p<0.001 respectively)., Conclusions: Patients seeking Essure removal had an impaired preoperative QoL. They experienced a significant QoL improvement at three months post-operation. These findings will help clinicians to inform patients about their expected postoperative functional status and QoL., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflicts of interest to disclose., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

Background: Symptomatic isolated carotid artery occlusions (ICAO) can lead to disability, recurrent stroke, and mortality, but natural history and best therapeutic management remain poorly known. The objective of this study was to describe our cohort of ICAO patients with an initial medical management., Methods: We conducted a retrospective study including consecutive patients admitted to our Comprehensive Stroke Center for ICAO within 24 h after stroke onset between January 2016 and September 2018. Patients with immediate endovascular therapy (EVT) were excluded. Medical treatment was based on anticoagulation (delayed by 24 h if intravenous thrombolysis was performed). 'Rescue' EVT was considered if first-week neurological deterioration (FWND) occurred., Results: Fifty-six patients were included, with a median National Institutes of Health Stroke Scale (NIHSS) of 3. Eleven patients (20%) had FWND during the first week, four benefited from rescue EVT. A mismatch volume > 40 cc on initial perfusion imaging and FLAIR vascular hyperintensities were associated with FWND (p = 0.007 and p = 0.009, respectively). Thirty-eight patients (69%) had a good outcome (modified Rankin Scale mRS 0-2) at 3 months, 36 (69%) had an excellent outcome (mRS 0-1). Seventeen patients (38%) had carotid patency on 3-month control imaging. Recurrences occurred in six (13%) of the survivors (mean follow-up: 13.6 months)., Conclusion: Our results suggest that the prognosis of patients with acute ICAO was favorable with a medical strategy, albeit a substantial rate of FWND and recurrence. FWND was well predicted by a core-perfusion mismatch volume > 40 cc. Randomized controlled trials are necessary to assess the benefit of EVT in ICAO.

Neurofilament light chain (NfL) has been demonstrated to correlate with multiple sclerosis disease severity as well as treatment response. Nevertheless, additional serum biomarkers are still needed to better differentiate disease activity from disease progression. The aim of our study was to assess serum glial fibrillary acid protein (s-GFAP) and neurofilament light chain (s-NfL) in a cohort of 129 multiple sclerosis (MS) patients. Eighteen primary progressive multiple sclerosis (PPMS) and 111 relapsing remitting MS (RRMS) were included. We showed that these 2 biomarkers were significantly correlated with each other (R = 0.72, p < 0.001). Moreover, both biomarkers were higher in PPMS than in RRMS even if multivariate analysis only confirmed this difference for s-GFAP (130.3 ± 72.8 pg/ml vs 83.4 ± 41.1 pg/ml, p = 0.008). Finally, s-GFAP was correlated with white matter lesion load and inversely correlated with WM and GM volume. Our results seem to confirm the added value of s-GFAP in the context of multiple sclerosis.