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Introduction: In recent years, pregabalin has received growing attention due to its abuse liability. The aim of this study was to further characterize patterns of pregabalin users from substance abuse treatment facilities and detect changes in users profile over the study period., Methods: The data source was the Observation des Produits Psychotropes Illicites ou Détournés de leur Utilisation Médicamenteuse (OPPIDUM) program, an annual, repeated, cross-sectional, nationwide, multicenter survey that collects consumption data from patients with substance use disorders. First, we described the characteristics of pregabalin users and their consumption patterns. We compared these data between 2008 and 2018 (P1) and 2019 and 2022 (P2). Second, we conducted a multiple correspondence analysis to identify profiles of users., Results: From 2008 to 2022, 291 pregabalin users (0.37% of all users) from 116 substance abuse treatment facilities were identified. The number of pregabalin users was lower than 15 per year in P1 (n = 89) and between 40 and 60 per year in P2 (n = 202). The number of users who reported pregabalin as the first substance leading to dependence increased significantly in P2 compared with P1 (p < 0.005). When comparing P2 with P1, there was a significant increase in precarity (p < 0.001), users in prison (p = 0.002), withdrawal symptoms (p < 0.001), dependence (p < 0.001), use of higher dose of pregabalin (p = 0.029), and acquisition by deal/street market (p < 0.001). The multiple correspondence analysis allowed for the identification of distinct profiles of pregabalin users: (i) a cluster with mainly users from P1, who presented a simple use of pregabalin, and were older (> 45 years), were involved in opioid agonist treatment (OAT), and obtained pregabalin legally; and (ii) a cluster with mainly users from P2, who presented pregabalin dependence, and were younger (< 26 years), reported pregabalin as the first substance leading to dependence, used doses higher than the market authorization, were in severe precarity, and were in prison., Conclusions: These data showed that the profile of pregabalin users has changed in the last years. Pregabalin use disorders also affect users without history of addiction., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Autism spectrum disorders (ASD) are neurodevelopmental disorders of varying intensity and disability. The reference health strategy in France for the care of young children with autism is day care hospital (DCH). As the number of places in DCH is insufficient, medically coordinated care programs by the mental health consultation centers (MHCC) are being developed in response., Objectives: Our objective is to evaluate the effectiveness of a medically coordinated care program in a MHCC versus the care in DCH of child psychiatry., Methods: Non-inferiority retrospective study comparing the evolution after one year of care of 20 ASD children divided into two groups DCH and MHCC. In the DCH ASD group, the child is taken care of two half-days a week in a day hospital with individual educational care. In the MHCC ASD group, the child benefits from a medically coordinated care program. The medical care is reinforced by more frequent and longer consultations with guidance offered to parents. In both groups, the child receives speech therapy and psychomotor therapy in private practice at the same rate. Comparison is made using a composite criterion associating CARS-2 and VABS-II. Non-inferiority of the medically coordinated care program in autism in reference to DCH was tested on the difference between the changes (DCH group variation - MHCC group variation) with a non-inferiority threshold of 10% of the initial value of each score., Results: We observed a reduction in autism severity at the CARS-2 and a moderate improvement in socio-adaptive behavior at the VABS-II in both groups. This trend was even more pronounced in the MHCC group than in the DCH group, but only the greater reduction in CARS-2 severity in the MHCC was statistically significant., Conclusions: As it is necessary to integrate the two scales into the composite criterion, it is not possible to retain the non-inferiority of the MHCC with care program. However, both those children followed in DCH and those in the MHCC care program progress. This shows the relevance of the care offered at the MHCC for children suffering from ASD, in the context of a growing lack of space in DCH. The continuation of this research work through multicenter studies with larger numbers could demonstrate the non-inferiority of coordinated care programs in the MHCC versus DCH. It would also allow subgroups to be set up, taking into account the initial characteristics of the children in order to have more precise indications concerning the relevance of each treatment., (Copyright © 2024 L'Encéphale, Paris. Published by Elsevier Masson SAS. All rights reserved.)

Introduction: Autologous fat transfer (AFT) is widely used to improve results of breast reconstructive surgery, but its safety is controversial. Our objective was to evaluate the oncologic safety of AFT in a homogeneous population of patients who underwent a total mastectomy with immediate reconstruction for breast cancer., Methods: We performed a retrospective cohort study by identifying all patients who underwent immediate breast reconstruction after mastectomy for breast cancer from 2007 to 2015 in our center. A patient group with AFT performed in the 24 months after mastectomy was compared to a control group., Results: Five hundred fifty cases were included, of whom 136 (24.7%) underwent at least one fat graft transfer. Median age was 51 years. Reconstruction was performed in 465 (84.5%) with an implant reconstruction. The median time from mastectomy to AFT was 13.8 months. The median follow up was 55.2 months. A total of 53 events were observed, including 10 (7.4%) in the AFT group and 43 (10.4%) in the control group. There was no difference in 5-year recurrence-free survival (RFS) between the groups. In the subgroup analysis, only lymph node involvement in patients who underwent AFT in the first 24 months after oncologic surgery appeared as a risk factor of recurrence. Among the 104 patients with lymph node involvement, 5-year RFS was 69.2% in patients with lipofilling vs 92.5% in patients without it (p = 0 0.0351)., Conclusion: Performing early lipofilling in primary breast reconstruction after mastectomy for cancer seems to be oncologically safe. Lymph node involvement increases the risk of recurrence in this population., 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., (© 2024 Published by Elsevier Ltd.)

Background: Elderly breast cancer (BC) patients have been underrepresented in clinical trials whereas ~60% of deaths from BC occur in women aged 70 years and older. Only limited data are available on the prognostic impact of age according to treatment, especially in the triple-negative (TN) and Her2-positive because of the lower frequency of these subtypes in elderly patients. We report herein the results of a multicenter retrospective study analyzing the prognostic impact of age according to treatment delivered in TN and Her2-positive BC patients of 70 years or older, including comparison by age groups., Methods: The medical records of 31,473 patients treated from January 1991 to December 2018 were retrieved from 13 French cancer centers for retrospective analysis. Our study population included all ≥70 patients with TN or Her2-positive BC treated by upfront surgery. Three age categories were determined: 70-74, 75-80, and > 80 years., Results: Of 528 patients included, 243 patients were 70-74 years old (46%), 172 were 75-80 years (32.6%) and 113 were >80 years (21.4%). Half the population (51.9%, 274 patients) were TN, 30.1% (159) Her2-positive/hormone receptors (HR)-positive, and, 18% (95) Her2-positive/endocrine receptors (ER)-negative BC. Advanced tumor stage was associated with older age but no other prognostic factors (tumor subtype, tumor grade, LVI). Adjuvant chemotherapy delivery was inversely proportional to age. With 49 months median follow-up, all patient outcomes (overall survival (OS), disease-free survival (DFS), breast cancer-specific survival (BCSS), and recurrence-free survival (RFS)) significantly decreased as age increased. In multivariate analysis, age >80, pT2-3 sizes, axillary macrometastases, lymphovascular involvement, and HR-negativity tumor negatively affected DFS and OS. Comparison between age >80 and <=80 years old showed worse RFS in patients aged > 80 (HR=1.771, p=0.031)., Conclusion: TN and Her2-positive subtypes occur at similar frequency in elderly patients. Older age is associated with more advanced tumor stage presentation. Chemotherapy use decreases with older age without worse other pejorative prognostic factors. Age >80, but not ≤80, independently affected DFS and OS., Competing Interests: The 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. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2023 Houvenaeghel, Cohen, Gonçalves, Berthelot, Chauvet, Faure, Classe, Jouve, Sabiani, Bannier, Tassy, Martino, Tallet and de Nonneville.)

(1) Background: The independent negative prognostic value of isolated tumor cells or micro-metastases in axillary lymph nodes has been established in triple-negative breast cancers (BC). However, the prognostic significance of pN0(i+) or pN1mi in HER2-positive BCs treated by primary surgery remains unexplored. Therefore, our objective was to investigate the impact of pN0(i+) or pN1mi in HER2-positive BC patients undergoing up-front surgery on their outcomes. (2) Methods: We retrospectively analyzed 23,650 patients treated in 13 French cancer centers from 1991 to 2013. pN status was categorized as pN0, pN0(i+), pN1mi, and pNmacro. The effect of pN0(i+) or pN1mi on outcomes was investigated both in the entire cohort of patients and in pT1a-b tumors. (3) Results: Of 1771 HER2-positive BC patients included, pN status distributed as follows: 1047 pN0 (59.1%), 60 pN0(i+) (3.4%), 118 pN1mi (6.7%), and 546 pN1 macro-metastases (30.8%). pN status was significantly associated with sentinel lymph node biopsy, axillary lymph node dissection, age, ER status, tumor grade, and size, lymphovascular invasion, adjuvant systemic therapy (ACt), and radiation therapy. With 61 months median follow-up (mean 63.2; CI 95% 61.5-64.9), only pN1 with macro-metastases was independently associated with a negative impact on overall, disease-free, recurrence-free, and metastasis-free survivals in multivariate analysis. In the pT1a-b subgroup including 474 patients, RFS was significantly decreased in multivariate analysis for pT1b BC without ACt (HR 2.365, 1.04-5.36, p = 0.039) and for pN0(i+)/pN1mi patients (HR 2.518, 1.03-6.14, p = 0.042). (4) Conclusions: Survival outcomes were not adversely affected by pN0(i+) and pN1mi in patients with HER2-positive BC. However, in the case of pT1a-b HER2-positive BC, a negative impact on RFS was observed specifically for patients with pN0(i+) and pN1mi diseases, particularly among those with pT1b tumors without ACt. Our findings highlight the importance of considering the pN0(i+) and pN1mi status in the decision-making process when discussing trastuzumab-based ACt for these patients.

Background: The aims of this study were to describe pharmacokinetic/pharmacodynamic target attainment in intensive care unit (ICU) patients treated with continuously infused ß -lactam antibiotics, their associated covariates, and the impact of dosage adjustment., Methods: This prospective, observational, cohort study was performed in three ICUs. Four ß -lactams were continuously infused, and therapeutic drug monitoring (TDM) was performed at days 1, 4, and 7. The primary pharmacokinetic/pharmacodynamic target was an unbound ß -lactam plasma concentration four times above the bacteria's minimal inhibitory concentration during the whole dosing interval. The demographic and clinical covariates associated with target attainment were evaluated., Results: A total of 170 patients were included (426 blood samples). The percentages of empirical ß -lactam underdosing at D1 were 66% for cefepime, 43% for cefotaxime, 47% for ceftazidime, and 14% for meropenem. Indexed creatinine clearance was independently associated with treatment underdose if increased (adjusted odds ratio per unit, 1.01; 95% CI, 1.00 to 1.01; p = 0.014) or overdose if decreased (adjusted odds ratio per unit, 0.95; 95% CI, 0.94 to 0.97; p < 0.001). Pharmacokinetic/pharmacodynamic target attainment was significantly increased after ß -lactam dosage adjustment between day 1 and day 4 vs. no adjustment (53.1% vs. 26.2%; p = 0.018)., Conclusions: This study increases our knowledge on the optimization of ß -lactam therapy in ICU patients. A large inter- and intra-patient variability in plasmatic concentrations was observed, leading to inadequate exposure. A combined indexed creatinine clearance and TDM approach enables adequate dosing for better pharmacokinetic/pharmacodynamic target attainment.

Background: Type 2 diabetes (T2D) and obesity induce left ventricular (LV) dysfunction. The underlying pathophysiological mechanisms remain unclear, but myocardial triglyceride content (MTGC) could be involved., Objectives: This study aimed to determine which clinical and biological factors are associated with increased MTGC and to establish whether MTGC is associated with early changes in LV function., Methods: A retrospective study was conducted using five previous prospective cohorts, leading to 338 subjects studied, including 208 well-phenotyped healthy volunteers and 130 subjects living with T2D and/or obesity. All the subjects underwent proton magnetic resonance spectroscopy and feature tracking cardiac magnetic resonance imaging to measure myocardial strain., Results: MTGC content increased with age, body mass index (BMI), waist circumference, T2D, obesity, hypertension, and dyslipidemia, but the only independent correlate found in multivariate analysis was BMI (p=0.01; R²=0.20). MTGC was correlated to LV diastolic dysfunction, notably with the global peak early diastolic circumferential strain rate (r=-0.17, p=0.003), the global peak late diastolic circumferential strain rate (r=0.40, p<0.0001) and global peak late diastolic longitudinal strain rate (r=0.24, p<0.0001). MTGC was also correlated to systolic dysfunction via end-systolic volume index (r=-0.34, p<0.0001) and stroke volume index (r=-0.31, p<0.0001), but not with longitudinal strain (r=0.009, p=0.88). Interestingly, the associations between MTGC and strain measures did not persist in multivariate analysis. Furthermore, MTGC was independently associated with LV end-systolic volume index (p=0.01, R²=0.29), LV end-diastolic volume index (p=0.04, R²=0.46), and LV mass (p=0.002, R²=0.58)., Conclusions: Predicting MTGC remains a challenge in routine clinical practice, as only BMI independently correlates with increased MTGC. MTGC may play a role in LV dysfunction but does not appear to be involved in the development of subclinical strain abnormalities., Competing Interests: The 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 © 2023 Soghomonian, Dutour, Kachenoura, Thuny, Lasbleiz, Ancel, Cristofari, Jouve, Simeoni, Kober, Bernard and Gaborit.)

Objective: Patients with systemic lupus erythematosus (SLE) display symptoms that are not always related to disease activity and may distort clinical trial results. Recently, a clinical categorization based on the presence of type 1 (inflammatory manifestations) and/or type 2 (widespread pain, fatigue, depression) symptoms has been proposed in SLE. Our aim was to develop a type 2 score derived from the Short-Form health survey (SF-36) to categorize SLE patients and to compare immunological and transcriptomic profiles between groups., Method: Seventeen items from the SF-36 were selected to build a type 2 score for 50 SLE patients (100 visits; LUPUCE cohort), and the SLEDAI was used to define type 1 symptoms. Patients were categorized into four groups: minimal (no symptoms), type 1, type 2, and mixed (both type 1 and type 2 symptoms). Clinical, immunological, and transcriptomic profiles were compared between the groups., Results: Type 2 scores ranged from 0 to 31, with a cutoff value of 14 (75th percentile). The sample categorization was minimal in 39%, type 1 in 37%, and type 2 in 9%, and mixed in 15%. Type 2 patients were older than minimal patients and had a longer disease duration than type 1 and mixed patients. Immunological data and modular interferon signatures did not differ between the groups., Conclusion: Patients with SLE can be categorized into four clinical groups using the SLEDAI score and our SF-36-derived type 2 score. This categorization is non-redundant with immunological or transcriptomic profiles and could prove useful to stratify patients in clinical trials. Key Points • A score derived from selected items of the SF-36 can be used to identify SLE patients with type 2 symptoms according to the Duke University categorization. • Using the SLEDAI and this type 2 score, SLE patients can be categorized into four clinical groups. • This categorization is not related to immunological activity or blood transcriptome profiles (and not to the interferon signature in particular). • This categorization could be useful in the daily care of patients as well as in clinical trials, for upstream patient stratification or for the interpretation of results., (© 2023. The Author(s), under exclusive licence to International League of Associations for Rheumatology (ILAR).)

Background: Tocilizumab and anakinra are anti-interleukin drugs to treat severe coronavirus disease 2019 (COVID-19) refractory to corticosteroids. However, no studies compared the efficacy of tocilizumab versus anakinra to guide the choice of the therapy in clinical practice. We aimed to compare the outcomes of COVID-19 patients treated with tocilizumab or anakinra., Methods: Our retrospective study was conducted in three French university hospitals between February 2021 and February 2022 and included all the consecutive hospitalized patients with a laboratory-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection assessed by RT-PCR who were treated with tocilizumab or anakinra. A propensity score matching was performed to minimize confounding effects due to the non-random allocation., Results: Among 235 patients (mean age, 72 years; 60.9% of male patients), the 28-day mortality (29.4% vs. 31.2%, p = 0.76), the in-hospital mortality (31.7% vs. 33.0%, p = 0.83), the high-flow oxygen requirement (17.5% vs. 18.3%, p = 0.86), the intensive care unit admission rate (30.8% vs. 22.2%, p = 0.30), and the mechanical ventilation rate (15.4% vs. 11.1%, p = 0.50) were similar in patients receiving tocilizumab and those receiving anakinra. After propensity score matching, the 28-day mortality (29.1% vs. 30.4%, p = 1) and the rate of high-flow oxygen requirement (10.1% vs. 21.5%, p = 0.081) did not differ between patients receiving tocilizumab or anakinra. Secondary infection rates were similar between the tocilizumab and anakinra groups (6.3% vs. 9.2%, p = 0.44)., Conclusion: Our study showed comparable efficacy and safety profiles of tocilizumab and anakinra to treat severe COVID-19., Competing Interests: GK has received from ROCHE-CHUGAI Research Grants <€20,000 and fees from Sobi France for scientific presentations <€4,000 and participated in a SOBI Advisory Board on COVID unpaid and an OLATEC Monitoring Board unpaid. 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 © 2023 Arcani, Correard, Suchon, Kaplanski, Jean, Cauchois, Leprince, Arcani, Seguier, De Sainte Marie, Andre, Koubi, Rossi, Gayet, Gobin, Garrido, Weiland, Jouve, Couderc, Villani and Daumas.)

Purpose: The study sought to estimate the prevalence of primary non-aortic lesions (PNAL) unrelated to extension of aortic dissection (AD) in a cohort of patients with Marfan syndrome (MFS)., Methods: Adult patients presenting with pathogenic FBN1 mutations and an available pan-aortic contrast-enhanced CTA in eight French MFS clinics from April to October 2018 were included. Clinical and radiological data, particularly the presence of aortic lesions and PNAL (including aneurysm and ectasia), were retrospectively analyzed., Results: Out of 138 patients, 28 (20.3%) had PNAL. In total, 27 aneurysms in 13 patients and 41 ectasias in 19 patients were reported mainly in the subclavian, iliac, and vertebral segments. Four patients (31%) with aneurysms and none with ectasia required prophylactic intervention during follow-up (median: 46 months). In multivariate analysis, factors associated with PNAL were history of AD (OR = 3.9, 95%CI: 1.3-12.1, p = 0.018), history of previous descending aortic surgery (OR = 10.3, 95%CI: 2.2-48.3, p = 0.003) and age (per 10 years OR = 1.6, 95%CI: 1.1-2.4, p = 0.008)., Conclusion: PNAL is not rare in MFS patients with evolutive aortic disease. Natural history may differ between aneurysms and ectasia, emphasizing the need for standardized definitions and systematic screening for PNAL.

Background: There is a scarcity of data exploring early breast cancer (eBC) in very young patients. We assessed shared and intrinsic prognostic factors in a large cohort of patients aged ≤35, compared to a control group aged 36 to 50., Methods: Patients ≤50 were retrospectively identified from a multicentric cohort of 23,134 eBC patients who underwent primary surgery between 1990 and 2014. Multivariate Cox analyses for DFS and OS were built. To assess the independent impact of age, 1 to 3 case-control analysis was performed by matching ≤35 and 36-50 years patients., Results: Of 6481 patients, 556 were aged ≤35, and 5925 from 36 to 50. Age ≤35 was associated with larger tumors, higher grade, ER-negativity, macroscopic lymph node involvement (pN + macro), lymphovascular invasion (LVI), mastectomy, and chemotherapy (CT) use. In multivariate analysis, age ≤35 was associated with worse DFS [HR 1.56, 95% CI 1.32-1.84; p < 0.001], and OS [HR 1.29, 95% CI 1.03-1.60; p = 0.025], as were high grade, large tumor, LVI, pN + macro, ER-negativity, period of diagnostic, and absence of ET or CT (for DFS). Adverse prognostic impact of age ≤35 was maintained in the case control-matched analysis for DFS [HR 1.56, 95%CI 1.28-1.91, p < 0.001], and OS [HR 1.33, 95%CI 1.02-1.73, p = 0.032]. When only considering patients ≤35, ER, tumor size, nodal status, and LVI were independently associated with survival in this subgroup., Conclusions: Age ≤35 is associated with less favorable presentation and more aggressive treatment strategies. Our results support the poor prognosis value of young age, which independently persisted when adjusting for other prognostic factors and treatments., Competing Interests: Declaration of competing interest Alexandre de Nonneville declares Gilead (lecture fees, congress invitations), Daiichi Sankyo (lecture fees, congress invitations), Seagen (consulting fees), Lilly (lecture fees, congress invitations, consulting fees, research grants paid to institution), Novartis (consulting fees), MSD (congress invitations, lecture fees), Pfizer (research grants paid to institution). No conflict of interest declared by others authors., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Purpose: Data about incidence, biological, and clinical characteristics of oligometastatic breast cancer (OMBC) are scarce. However, these data are essential in determining optimal treatment strategy. Gaining knowledge of these elements means observing and describing large, recent, and consecutive series of OMBC in their natural history., Methods: We collected data retrospectively at our institution from 998 consecutive patients diagnosed and treated with synchronous or metachronous metastatic breast cancer (MBC) between January 2014 and December 2018. The only criterion used to define OMBC was the presence of one to five metastases at diagnosis., Results: Of 998 MBC, 15.8% were classified OMBC. Among these, 88% had one to three metastases, and 86.7% had only one organ involved. Bone metastases were present in 52.5% of cases, 20.9% had progression to lymph nodes, 14.6% to the liver, 13.3% to the brain, 8.2% to the lungs, and 3.8% had other metastases. 55.7% had HR+/HER2- OMBC, 25.3% had HER2+OMBC, and 19% had HR-/HER2- OMBC. The HR+/HER2- subtype statistically correlated with bone metastases (p = 0.001), the HER2+subtype with brain lesions (p = 0.001), and the HR-/HER2- subtype with lymph node metastases (p = 0.008). Visceral metastases were not statistically associated with any OMBC subtypes (p = 0.186). OMBC-SBR grade III was proportionally higher than in the ESME series of 22,109 MBC (49.4% vs. 35.1%, p < 0.001)., Conclusion: OMBC is a heterogeneous entity whose incidence is higher than has commonly been published. Not an indolent disease, each subgroup, with its biological and anatomical characteristics, merits specific management., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Combining fat graft with platelet derived products is now common practice in regenerative surgery. We proposed to assess the safety and efficacy of Platelet-Rich Plasma (PRP) addition to a micro-lipofilling protocol for facial treatment of patients suffering from Systemic Sclerosis (SSc)., Objective: Main objective was to evaluate the improvement of the Mouth Handicap In Systemic Sclerosis (MHISS) scale score at 6 months post-therapy., Method: Included SSc patients had a MHISS score equal or up to 20. Surgery was performed under general anesthesia. Micro-fat and PRP (CCA-NA from DEPA Classification) were mixed in a 70/30 ratio, before injection in peri-oral sites according to a specific protocol. Efficacy criteria were recorded at baseline, 3 and 6 months. Moreover, we compared this cohort (current study) to a former (2015) non-enriched micro-lipofilling cohort in the same indication, using the same protocol., Results: Thirteen women patients with mean age of 53.2 years (±14.3) have been included. At baseline, mean MHISS score was 29.5 (±8.7) and significantly decreased to 22.5 (±7.8) at 6 months (P=0.016), corresponding to a 22.0% of improvement from baseline, with a mean decrease of 6.5 points (±7.5) at 6 months. Patients received a mean volume of 30.8ml PRP-micro-fat (±8.1ml)., Conclusion: PRP addition appeared beneficial, however, controlled studies are required to determine its superiority to facial micro-lipofilling., (Copyright © 2022 Elsevier Masson SAS. All rights reserved.)

Background: Results of IBCSG-23-01-trial which included breast cancer patients with involved sentinel nodes (SN) by isolated-tumor-cells or micro-metastases supported the non-inferiority of completion axillary-lymph-node-dissection (cALND) omission. However, current data are considered insufficient to avoid cALND for all patients with SN-micro-metastases., Methods: To investigate the impact of cALND omission on disease-free-survival (DFS) and overall survival (OS), we analyzed a cohort of 1421 patients <75 years old with SN-micro-metastases who underwent breast conservative surgery (BCS). We used inverse probability of treatment weighting (IPTW) to obtain adjusted Kaplan-Meier estimators representing the experience in the analysis cohort, based on whether all or none had been subject to cALND omission., Results: Weighted log-rank tests comparing adjusted Kaplan-Meier survival curves showed significant differences in OS (p-value = 0.002) and borderline significant differences in DFS (p-value = 0.090) between cALND omission versus cALND. Cox's regression using stabilized IPTW evidenced an average increase in the risk of death associated with cALND omission (HR = 2.77, CI95% = 1.36-5.66). Subgroup analyses suggest that the rates of recurrence and death associated with cALND omission increase substantially after a large period of time in the half sample of women less likely to miss cALND., Conclusions: Using IPTW to estimate the causal treatment effect of cALND in a large retrospective cohort, we concluded cALND omission is associated with an increased risk of recurrence and death in women of <75 years old treated by BCS in the absence of a large consensus in favor of omitting cALND. These results are particularly contributive for patients treated by BCS where cALND omission rates increase over time., (© 2022 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Purpose: Local ablative treatment (LAT) is increasingly combined with systemic therapy in oligometastatic breast cancer (OMBC), without a high-level evidence to support this strategy. We evaluated the addition of LAT to systemic treatment in terms of progression-free survival (PFS) and overall survival (OS). Secondary endpoints were local control (LC) and toxicity. We sought to identify prognostic factors associated with longer OS and PFS., Methods and Materials: We identified consecutive patients treated between 2014 and 2018 for synchronous or metachronous OMBC (defined as ≤ 5 metastases). LAT included stereotactic body radiation therapy (SBRT) and volumetric modulated arc therapy (VMAT), surgery, cryotherapy and percutaneous radiofrequency ablation (PRA). PFS and OS were calculated, and Cox regression models analyzed for potential predictors of survival., Results: One hundred two patients were included (no-LAT, n = 62; LAT, n = 40). Sixty-four metastases received LAT. Median follow-up was 50.4 months (95% CI [44.4; 53.4]). One patient experienced grade 3 toxicity in the LAT group. Five-year PFS and OS were 34.75% (95% CI [24.42-45.26]) and 63.21% (95% CI [50.69-73.37]) respectively. Patients receiving both LAT and systemic therapy had longer PFS and OS than those with no-LAT ([HR 0.39, p = 0.002]) and ([HR 0.31, p = 0.01]). The use of LAT, HER2-positive status and hormone-receptor positivity were associated with longer PFS and OS whereas liver metastases led to worse PFS., Conclusions: LAT was associated with improved outcomes in OMBC when added to systemic treatment, without significantly increasing toxicity. The prognostic factors identified to extend PFS and OS may help guide clinicians in selecting patients for LAT., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Satisfactory treatment is often lacking for spasticity, a highly prevalent motor disorder in patients with spinal cord injury (SCI). Low concentrations of riluzole potently reduce the persistent sodium current, the post-SCI increase in which contributes to spasticity. The repurposing of this drug may therefore constitute a useful potential therapeutic option for relieving SCI patients suffering from chronic traumatic spasticity., Objective: RILUSCI is a phase 1b-2b trial designed to assess whether riluzole is a safe and biologically effective means of managing spasticity in adult patients with traumatic chronic SCI., Methods: In this multicenter double-blind trial, adults (aged 18-65 years) suffering from spasticity after SCI (target enrollment: 90 participants) will be randomly assigned to be given either a placebo or a recommended daily oral dose of riluzole for two weeks. The latter dose will be previously determined in phase 1b of the study by performing double-blind dose-finding tests using a Bayesian continuous reassessment method. The primary endpoint of the trial will be an improvement in the Modified Ashworth Score (MAS) or the Numerical Rating Score (NRS) quantifying spasticity. The secondary outcomes will be based on the safety and pharmacokinetics of riluzole as well as its impact on muscle spasms, pain, bladder dysfunction and quality of life. Analyses will be performed before, during and after the treatment and the placebo-controlled period., Conclusion: To the best of our knowledge, this clinical trial will be the first to document the safety and efficacy of riluzole as a means of reducing spasticity in patients with chronic SCI., Trial Registration: The clinical trial, which is already in progress, was registered on the ClinicalTrials.gov website on August 9, 2016 under the registration number NCT02859792., Trial Sponsor: Assistance Publique-Hôpitaux de Marseille., Competing Interests: The authors declare no competing interests, (Copyright: © 2023 Cotinat et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Deprivation generates many health inequalities. This has to be taken in account to enhance appropriate access to care. This study aimed to develop and validate a pediatric individual-level index measuring deprivation, usable in clinical practice and in public health., Methods: The French Individual Child Deprivation Index (FrenChILD-Index) was designed in four phases: item generation then reduction using the literature review and expert opinions, and index derivation then validation using a cross-sectional study in two emergency departments. During these last two phases, concordance with a blinded evaluation by an expert enabled us to determine thresholds for two levels of moderate and severe deprivation., Results: The generation and reduction phases retained 13 items. These were administered to 986 children for the derivation and validation phases. In the validation phase, the final 12 items of the FrenChILD-Index showed for moderate deprivation (requiring single specific care for deprived children) a sensitivity of 96.0% [92.6; 98.7] and specificity of 68.3% [65.2; 71.4]. For severe deprivation (requiring a multidisciplinary level of care), the sensitivity was 96.3% [92.7; 100] and specificity was 91.1% [89.2; 92.9]., Conclusions: The FrenChILD-Index is the first pediatric individual-level index of deprivation validated in Europe. It enables clinical practice to address the social determinants of health and meet public health goals.

Macrophages play a key role in the inflammatory phase of wound repair and foreign body reactions-two important processes in the Masquelet-induced membrane technique for extremity reconstruction. The macrophage response depends largely on the nature of the biomaterials implanted. However, little is known about the influence of the macrophage microenvironment on the osteogenic properties of the induced membrane or subsequent bone regeneration. We used metakaolin, an immunogenic material, as an alternative spacer to standard polymethylmethacrylate (PMMA) in a Masquelet model in rats. Four weeks after implantation, the PMMA- and metakaolin-induced membranes were harvested, and their osteogenic properties and macrophage microenvironments were investigated by histology, immunohistochemistry, mass spectroscopy and gene expression analysis. The metakaolin spacer induced membranes with higher levels of two potent pro-osteogenic factors, transforming growth factor-β (TGF-β) and bone morphogenic protein-2 (BMP-2). These alternative membranes thus had greater osteogenic activity, which was accompanied by a significant expansion of the total macrophage population, including both the M1-like and M2-like subtypes. Microcomputed tomographic analysis showed that metakaolin-induced membranes supported bone regeneration more effectively than PMMA-induced membranes through better callus properties (+58%), although this difference was not significant. This study provides the first evidence of the influence of the immune microenvironment on the osteogenic properties of the induced membranes.

No injection treatment has been proven to be effective in wrist osteoarthritis. When conservative measures fail, its management involves invasive surgery. Emergence of biotherapies based on adipose derived stem cells (ADSC) offers promising treatments for chondral degenerative diseases. Microfat (MF) and platelets-rich plasma (PRP) mixture, rich in growth factors and ADSC could be a minimally invasive injectable option in the treatment of wrist osteoarthritis. The aim of this uncontrolled prospective study was to evaluate the safety of a 4 mL autologous MF-PRP intra-articular injection, performed under local anesthesia. The secondary purpose was to describe the clinical and MRI results at 12 months of follow-up. Patients' data collected were: occurrence of adverse effects, Visual analog scale (VAS), Disabilities of the Arm, Shoulder and Hand score (DASH) and Patient-Rated Wrist Evaluation (PRWE) scores, wrist strength, wrist range of motion and 5-level satisfaction scale. No serious adverse event was recorded. A statistically significant decrease in pain, DASH, PRWE and force was observed at each follow-up. Our preliminary results suggest that intra-articular autologous MF and PRP injection may be a new therapeutic strategy for wrist osteoarthritis resistant to medical symptomatic treatment prior to surgical interventions., Competing Interests: J.M. received honorarium for educational support from FIDIA, HORIBA ARTHREX and MACOPHARMA. These manufacturers had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results. Other authors did not declare any conflict of interest.

Introduction: Welding fumes (WF) are a complex mixture of gas and particles. Action of occupational exposure to WF on cardiovascular system has been recently studied as for noise., Research Question: The main objectives of our study are therefore to evaluate the impact of exposure to WF, noise, and combined WF and noise on autonomic nervous system as assessed by heart rate variability (HRV)., Methods: The study groups were 16 welders and eight airport workers (as a control group). All the participants underwent ambulatory electrocardiogram, personal WF, and noise exposure monitoring, respectively, with dust track and calibrated noise dosimeter during workday. Atmospheric environmental assessments at workplaces have been also performed. HRV parameters were summarized for all the workday and hourly. Correlation tests were used to examine relation between HRV parameters and levels of noise exposure in the two population. Analysis of covariance (ANCOVA) was used for mean of each HRV parameters., Results: For HRV parameters, we found significant higher levels for mean range of high frequency (HF), standard deviation of normal-to-normal R-R interval (SDNN), and root mean square of successive heartbeat interval difference (RMSSD) in welders which suggested an imbalance between sympathetic and parasympathetic nervous system in this population. For relation between noise and HRV parameters, we noted that levels of low frequency (LF), HF, and SDNN were significantly correlated with mean noise levels for welders (respectively, r = 0.62, r = 0.357, r = 0.48), not in control group. Using ANCOVA, we found that working as a welder significantly increases mean of HF ( p = 0.01) and RMSSD ( p = 0.02) and decreases in LF/HF ( p = 0.008). Indeed, the interaction between exposure to WF and mean noise levels for HF ( p = 0.005), LF/HF ( p = 0.01), and RMSSD ( p = 0.007) was significant., Conclusion: This study shows an impact of WF and noise on ANS balance. One hypothesis is WF exposure could increase sensibility to noise exposure on autonomic nervous system or there is a synergic effect., Competing Interests: The 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 © 2022 Lucas, Guerrero, Jouve, Hery, Capellmann and Mansourati.)

Environmental influence on intelligence quotient (IQ) is poorly understood in developing countries. We conducted the first cross-sectional investigation to assess the role of socio-economic and environmental factors on schoolchildren's IQ in Jalalabad, Afghanistan. A representative sample of 245 schoolchildren aged 7-15 was randomly selected in five schools. Children's records included: non-verbal IQ TONI-1 scale, body mass index, socio-economic status, and further environmental indicators (water supply, proximity to a heavy-traffic road, use of surma traditional cosmetics). The mean age of the children was 11.7 years old (±2.0 years), and 70.2% and 29.8% were male and female, respectively. The children's mean IQ was 83.8 (±12.6). In total, 37 (14.9%) of the children were overweight, 78 (31.5%) were living below the USD 1.25 poverty line, 133 (53.6%) used tap water supply, 76 (30.6%) used surma, and 166 (66.9%) were exposed to heavy road traffic. The children's IQ was significantly and independently lowered by tap water use (-3.9; 95% CI [-7.1; -0.6]) and by aging (-1.4; 95% CI [-2.2; -0.6]), as revealed in multivariate analysis, independently of gender, socio-economic status, exposure to heavy road traffic, overweight status, and surma use. Lower IQ among older children is possibly attributed to chronic stress experienced by adolescents due to living conditions in Afghanistan. While using tap water prevents fecal peril, it may expose children to toxic elements such as lead which is known to lower their intellectual development.

Objective: To assess the superiority of adipose tissue-derived stromal vascular fraction (AD-SVF) injection into the fingers vs placebo in reducing hand disability in systemic sclerosis (SSc) patients., Methods: We performed a double-blind, multicentre, phase II trial from October 2015 to January 2018 in France. SSc patients with a Cochin Hand Function Scale (CHFS) ≥20/90 were randomized 1:1 to receive injection of AD-SVF or placebo. AD-SVF was obtained using the automated processing Celution 800/CRS system. The placebo was lactated Ringer's solution. The primary efficacy end point was the change of the CHFS score from baseline to 3 months. Secondary efficacy endpoints included the CHFS score at 6 months, hand function, vasculopathy, hand pain, skin fibrosis, sensitivity of the finger pulps, Scleroderma Health Assessment Questionnaire, patients and physician satisfaction, and safety., Results: Forty patients were randomized. The AD-SVF and placebo groups were comparable for age, sex ratio, disease duration, skin fibrosis of the hands and main cause of hand disability. After 3 months' follow-up, hand function significantly improved in both groups with no between-group difference of CHFS (mean change of -9.2 [12.2] in the AD-SVF group vs -7.6 [13.2] in the placebo group). At 6 months, hand function improved in both groups., Conclusion: This study showed an improvement of hand function in both groups over time, with no superiority of the AD-SVF. Considering the limits of this trial, studies on a larger population of patients with homogeneous phenotype and hand handicap should be encouraged to accurately assess the benefit of AD-SVF therapy., Trial Registration: ClinicalTrials.gov, https://clinicaltrials.gov, NCT02558543. Registered on September 24, 2015., (© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Introduction: We report on our experience of using Helical Tomotherapy (HT) in the context of post-mastectomy radiation therapy (PMRT) with or without immediate implant-based breast Reconstruction (IBR)., Material and Methods: The study included a total of 173 patients who underwent PMRT with HT between 2013 and 2015 in our institution (87 immediate breast reconstructions with retropectoral implants (IBR + ), 86 without reconstructions (IBR-)). The chest wall target volume included subcutaneous tissue and pectoralis muscle and excluded the posterior region of the implant as well as the ribs., Results: Median time to initiation of the first adjuvant treatment from mastectomy was similar between the two groups (p = 0.134). Dose coverage to the chest wall was significantly improved for the IBR + group (V95% = 95.1 % versus 92.0 %; p < 0.0001). The irradiated volume of the ipsilateral lung was significantly decreased in the IBR + group with a median V20Gy of 11.6 %, compared to 15.2 % for the control group (p < 0.0001). The median heart V15Gy was also significantly lower in the IBR + group than in the control group (1.7 vs 2.5 %; p = 0.0280). The reconstruction failure rate was 14.9% (n = 13). After a median follow-up of 65 months, loco regional recurrence rate was low in both groups: 3 patients (3.4%) in the IBR + group and 5 patients (5.8%) in the control group, without any local recurrence in the posterior part of the implant., Conclusions: The presence of a breast implant reduces cardiac and pulmonary doses during Tomotherapy irradiation, without compromising oncological outcomes., Competing Interests: 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., (© 2022 The Author(s).)

Medical use of cannabis has been receiving growing attention over the last few decades in modern medicine. As we know that the endocannabinoid system is largely involved in neurological disorders, we focused on the scientific rationale of medical cannabis in three neurological disorders: amyotrophic lateral sclerosis, Parkinson's disease, and Alzheimer's disease through pharmacological plausibility, clinical studies, and patients' view. Clinical studies (randomized controlled trials, open-label studies, cohorts, and case reports) exploring medical cannabis in these disorders show different results depending on the methods and outcomes. Some show benefits on motor symptoms and others on non-motor symptoms and quality of life. Concerning patients' view, several web surveys were collected, highlighting the real use of cannabis to relieve symptoms of neurological disorders, mostly outside a medical pathway. This anarchic use keeps questioning particularly in terms of risks: consumption of street cannabis, drug-drug interactions with usual medical treatment, consideration of medical history, and adverse reactions (psychiatric, respiratory, cardiovascular disorders, etc.), underlining the importance of a medical supervision. To date, most scientific data support the therapeutic potential of cannabis in neurological disorders. As far as patients and patients' associations are calling for it, there is an urgent need to manage clinical studies to provide stronger evidence and secure medical cannabis use., Competing Interests: The 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 © 2022 Lacroix, Alleman-Brimault, Zalta, Rouby, Cassé-Perrot, Jouve, Attolini, Guilhaumou, Micallef and Blin.)

Background: During isotretinoin treatment, special attention is required to detect any symptom or change in the mental health of patients. The monitoring is complex for adolescents because of confounding factors such as mood changes associated with adolescence and puberty and the higher psychosocial impairment due to the acne itself., Aim: To determine the utility of the Adolescent Depression Rating Scale (ADRS) for monitoring symptoms in adolescents before and during isotretinoin treatment in dermatology real-life practice., Methods: This was a national, multicentre prospective study that enrolled a random sample of dermatologists treating adolescents. An algorithm including ADRS score and its changes between consecutive visits was used. At each visit, dermatologists rated their satisfaction with ADRS and its ease of use, while patients rated the acceptability of the ADRS., Results: In total, 70 dermatologists used the algorithm for 1227 visits of 283 adolescents receiving isotretinoin. Of these 70 dermatologists, 80.8% were satisfied/very satisfied with the ADRS, 82.7% considered the use of the ADRS in clinical practice to be easy/very easy and 75% considered that the ADRS enabled them to discuss more easily the risk of depression with their patients. For the patients, acceptability of the ADRS was considered good by 93.8%., Conclusions: The implementation of the ADRS could be valuable in dermatology practice, optimizing the monitoring of patients and the good use of isotretinoin., (© 2021 British Association of Dermatologists.)

Perianal fistulas in Crohn's disease are frequent and disabling, with a major impact on patients' quality of life. Cell-based therapy using mesenchymal stem cells represents new hope for these patients, but long-term efficacy remains challenging. In a pilot study, including patients with refractory complex perianal fistulas, autologous adipose-derived stromal vascular fraction (ADSVF) combined with microfat achieved combined remission in 60% of cases, with a good safety profile at 1 year. The purpose of this study is to assess whether these results were maintained at longer term. The safety and efficacy data of the ten patients were evaluated retrospectively 3 years after injection on the basis of clinical and radiological data. MRI were analysed according to the MAGNIFI-CD score. No adverse event was attributed to the experimental stem-cell treatment. Combined remission was achieved in 7 patients (70%) and associated with a significant improvement in the MAGNIFI-CD MRI score. In conclusion, the safety and efficacy of ADSVF and microfat injection in Crohn's disease fistulas were maintained at 3 years, demonstrating that this innovative strategy is effective in producing a long-lasting healing effect. The ongoing multicentre randomized placebo-controlled trial (NCT04010526) will be helpful to define the place for this approach in the current therapeutic arsenal., (© 2022. The Author(s).)

The BDNF Val66Met gene polymorphism is a relevant factor explaining inter-individual differences to TMS responses in studies of the motor system. However, whether this variant also contributes to TMS-induced memory effects, as well as their underlying brain mechanisms, remains unexplored. In this investigation, we applied rTMS during encoding of a visual memory task either over the left frontal cortex (LFC; experimental condition) or the cranial vertex (control condition). Subsequently, individuals underwent a recognition memory phase during a functional MRI acquisition. We included 43 young volunteers and classified them as 19 Met allele carriers and 24 as Val/Val individuals. The results revealed that rTMS delivered over LFC compared to vertex stimulation resulted in reduced memory performance only amongst Val/Val allele carriers. This genetic group also exhibited greater fMRI brain activity during memory recognition, mainly over frontal regions, which was positively associated with cognitive performance. We concluded that BDNF Val66Met gene polymorphism, known to exert a significant effect on neuroplasticity, modulates the impact of rTMS both at the cognitive as well as at the associated brain networks expression levels. This data provides new insights on the brain mechanisms explaining cognitive inter-individual differences to TMS, and may inform future, more individually-tailored rTMS interventions., (© 2022. The Author(s).)

Abstract: Our study aimed to develop and validate a real-time crowding composite scale for pediatric emergency department (PED). The study took place in one teaching PED for 2 months. The outcome was the perception of crowding evaluated by triage nurses and pediatricians on a 10-level Likert scale. Triage nurses evaluated crowding at each moment of a child's admission and pediatrician at each moment of a child's discharge. The outcome was the hourly mean of all evaluations of crowding (hourly crowding perception). For analysis, originally, we only selected hours during which more than 2 nurses and more than 2 pediatricians evaluated crowding and, moreover, during which evaluations were the most consensual. As predictors, we used hourly means of 10 objective crowding indicators previously selected as consensual in a published French national Delphi study and collected automatically in our software system. The model (SOTU-PED) was developed over a 1-month data set using a backward multivariable linear regression model. Then, we applied the SOTU-PED model on a 1-month validation data set. During the study period, 7341 children were admitted in the PED. The outcome was available for 1352/1392 hours, among which 639 were included in the analysis as "consensual hours." Five indicators were included in the final model, the SOTU-PED (R2 = 0.718). On the validation data set, the correlation between the outcome (perception of crowding) and the SOTU-PED was 0.824. To predict crowded hours (hourly crowding perception >5), the area under the curve was 0.957 (0.933-0.980). The positive and negative likelihood ratios were 8.16 (3.82-17.43) and 0.153 (0.111-0.223), respectively. Using a simple model, it is possible to estimate in real time how crowded a PED is., Competing Interests: Disclosure: The authors declare no conflict of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Based on results of clinical trials, completion ALND (cALND) is frequently not performed for patients with breast conservation therapy and one or two involved sentinel nodes (SN) by micro- or macro-metastases. However, there were limitations despite a conclusion of non-inferiority for cALND omission. No trial had included patients with SN macro-metastases and total mastectomy or with >2 SN macro-metastases. The aim of the study was too analyze treatment delivered and pathologic results of patients included in SERC trial. SERC trial is a multicenter randomized non-inferiority phase-3 trial comparing no cALND with cALND in cT0-1-2, cN0 patients with SN ITC (isolated tumor cells) or micro-metastases or macro-metastases, mastectomy or breast conservative surgery. We randomized 1855 patients, 929 to receive cALND and 926 SLNB alone. No significant differences in patient's and tumor characteristics, type of surgery, and adjuvant chemotherapy (AC) were observed between the two arms. Rates of involved SN nodes by ITC, micro-metastases, and macro-metastases were 5.91%, 28.12%, and 65.97%, respectively, without significant difference between two arms for all criteria. In multivariate analysis, two factors were associated with higher positive non-SN rate: no AC versus AC administered after ALND (OR = 3.32, p < 0.0001) and >2 involved SN versus ≤2 (OR = 3.45, p = 0.0258). Crude rates of positive NSN were 17.62% (74/420) and 26.45% (73/276) for patient's eligible and non-eligible to ACOSOG-Z0011 trial. No significant differences in patient's and tumor characteristics and treatment delivered were observed between the two arms. Higher positive-NSN rate was observed for patients with AC performed after ALND (17.65% for SN micro-metastases, 35.22% for SN macro-metastases) in comparison with AC administered before ALND., (© 2021. The Author(s).)

Purpose: To compare a single abdominal microfat (MF) injection mixed or not with platelet-rich plasma (PRP) Low Dose (LD) or High Dose (HD) in order to improve MRI parameters, alleviate pain and enhance functional capacity in knee osteoarthritis., Methods: Patients with symptomatic grade 2 to 4 knee osteoarthritis according to the International Cartilage Repair Society MRI classification were selected. They were prospectively assessed at baseline and at 3 and 6 months of follow-up. The primary endpoint was change in the maximum of value of cartilage relaxation time in T2 mapping sequences (T2max) at 3 months. Secondary endpoints were MRI grade severity and joint space assessment, Western Ontario and McMaster Universities Arthritis Index score, pain evaluation, knee range of motion, and patients' satisfaction. Adverse events were also collected. The complete cell counts and growth factors content of injected products were assessed to analyze their potential relationship with MRI and clinical outcomes., Results: Three groups of 10 patients received a single injection of 10 cc of a mix (1:1) containing MF-Saline, MF-PRP LD or MF-PRP HD. T2max did not change significantly over the time for any of the groups. All treatments significantly improved knee functional status and symptom relief at 3 and 6 months. All patients were responders in the MF/PRP HD at 3 months and significantly higher compared to MF/PRP LD. Half of the injected PRP in the MF/PRP LD group displayed red blood cell contamination of over 8%, which was correlated with an impairment of T2max., Conclusion: A single intra-articular injection of MF with or without PRP is safe and may offer a significant clinical improvement in patients with osteoarthritis., Level of Evidence: 2; randomized double-blind comparative parallel-group trial (RCT No.: NCT04352075)., (Copyright © 2021 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.)

Objective: To evaluate the relevance of transcranial magnetic stimulation (TMS) using triple stimulation technique (TST) to assess corticospinal function in amyotrophic lateral sclerosis (ALS) in a large-scale multicenter study., Methods: Six ALS centers performed TST and conventional TMS in upper limbs in 98 ALS patients during their first visit to the center. Clinical evaluation of patients included the revised ALS Functional Rating Scale (ALSFRS-R) and upper motor neuron (UMN) score., Results: TST amplitude ratio was decreased in 62% of patients whereas conventional TMS amplitude ratio was decreased in 25% of patients and central motor conduction time was increased in 16% of patients. TST amplitude ratio was correlated with ALSFRS-R and UMN score. TST amplitude ratio results were not different between the centers., Conclusions: TST is a TMS technique applicable in daily clinical practice in ALS centers for the detection of UMN dysfunction, more sensitive than conventional TMS and related to the clinical condition of the patients., Significance: This multicenter study shows that TST can be a routine clinical tool to evaluate UMN dysfunction at the diagnostic assessment of ALS patients., 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 © 2021 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Does oligometastatic breast cancer (OMBC) deserve a dedicated treatment? Although some authors recommend multidisciplinary management of OMBC with a curative intent, there is no evidence proving this strategy beneficial in the absence of a randomized trial. The existing literature sheds little light on OMBC. Incidence is unknown; data available are either obsolete or biased; there is no consensus on the definition of OMBC and metastatic sites, nor on necessary imaging techniques. However, certain proposals merit consideration. Knowledge of eventual specific OMBC biological characteristics is limited to circulating tumor cell (CTC) counts. Given the data available for other cancers, studies on microRNAs (miRNAs), circulating tumor DNA (ctDNA) and genomic alterations should be developed Finally, safe and effective therapies do exist, but results of randomized trials will not be available for many years. Prospective observational cohort studies need to be implemented., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2021 Institut Claudius Regaud - IUCT-Oncopole. Published by Elsevier Ltd.. All rights reserved.)

We evaluated the age-specific mortality of unselected adult outpatients infected with SARS-CoV-2 treated early in a dedicated COVID-19 day hospital and we assessed whether the use of hydroxychloroquine (HCQ) + azithromycin (AZ) was associated with improved survival in this cohort. A retrospective monocentric cohort study was conducted in the day hospital of our center from March to December 2020 in adults with PCR-proven infection who were treated as outpatients with a standardized protocol. The primary endpoint was 6-week mortality, and secondary endpoints were transfer to the intensive care unit and hospitalization rate. Among 10,429 patients (median age, 45 [IQR 32-57] years; 5597 [53.7%] women), 16 died (0.15%). The infection fatality rate was 0.06% among the 8315 patients treated with HCQ+AZ. No deaths occurred among the 8414 patients younger than 60 years. Older age and male sex were associated with a higher risk of death, ICU transfer, and hospitalization. Treatment with HCQ+AZ (0.17 [0.06-0.48]) was associated with a lower risk of death, independently of age, sex and epidemic period. Meta-analysis evidenced consistency with 4 previous outpatient studies (32,124 patients-Odds ratio 0.31 [0.20-0.47], I 2 = 0%). Early ambulatory treatment of COVID-19 with HCQ+AZ as a standard of care is associated with very low mortality, and HCQ+AZ improve COVID-19 survival compared to other regimens., Competing Interests: The authors declare no conflict of interest. The funders/sponsors had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; or decision to submit the manuscript for publication. Funding sources had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript. Our group used widely available generic drugs distributed by many pharmaceutical companies., (© 2021 The Author(s). Published by IMR Press.)

More than half of children who have autism spectrum disorder (ASD) suffer from motor impairment. In a retrospective study, the authors investigated the effect of a body-mediated workshop with dance movement therapy (DMT) on the motor skills and social skills of children with ASD by comparing 10 autistic children aged 7 to 10 years who benefited from DMT with 10 autistic children in a control group. Scores on the Movement Assessment Battery for Children and the Vineland Adaptive Behavior Scale were compared. The body-mediated workshop had significant benefits for motricity, especially manual dexterity, and for relational skills. A body-mediated workshop may have a multimodal effect and requires transmodal training. Regarding the mechanisms that explain the benefits and the cascading effect, the roles of imitation and multimodal connections are important.

Background: Muscle strength decreases as kidney failure progresses. Low muscle strength affects more than 50% of hemodialysis patients and leads to daily life activities impairment. In the general population, numerous studies have linked low 25OH-vitamin D (25OHD) concentrations to the loss of the muscle strength and low physical performances. Data on native vitamin D and muscle function are scarce in the chronic kidney disease (CKD) population, but low 25OHD levels have been associated with poor muscle strength. We present in this article the protocol of an ongoing study named VITADIAL testing if cholecalciferol supplementation in hemodialysis patients with low 25OHD improves their muscle strength., Methods/design: VITADIAL is a prospective open randomized French multicenter study. All patients will have 25OHD levels ≤50nmol/L at randomization. One group will receive 100,000 UI cholecalciferol once a month during 6 months; the other group will receive no treatment during 6 months. In order to randomize patients with 25OHD ≤50nmol/L, supplemented patients will undergo a 3 months wash-out period renewable 3 times (maximum of 12 months wash-out) until 25OHD reaches a level ≤50nmol/L. The main objective of this study is to analyze if a 6-month period of oral cholecalciferol (i.e., native vitamin D) supplementation improves muscle strength of hemodialysis patients with low 25OHD vitamin D levels. Muscle strength will be assessed at 0, 3, and 6 months, by handgrip strength measured with a quantitative dynamometer. Secondary objectives are (1) to analyze 25OHD plasma levels after vitamin D wash-out and/or supplementation, as well as factors associated with 25OHD lowering speed during wash-out, and (2) to analyze if this supplementation improves patient's autonomy, reduces frailty risk, and improves quality of life. Fifty-four patients are needed in each group to meet our main objective., Discussion: In the general population, around 30 randomized studies analyzed the effects of vitamin D supplementation on muscle strength. These studies had very different designs, sizes, and studied population. Globally, these studies and the meta-analysis of studies favor a beneficial effect of vitamin D supplementation on muscle strength, but this effect is mainly found in the subgroup of aged patients and those with the lowest 25OHD concentrations at inclusion. We reported a positive independent association between 25OHD and handgrip strength in a population of 130 hemodialysis patients in a dose-dependent manner. In our cohort, a plateau effect was observed above 75 nmol/L. Only two randomized studies analyzed the effect of native vitamin D supplementation on muscle strength in hemodialysis patients, but unfortunately, these two studies were underpowered. VITADIAL is a trial specifically designed to assess whether cholecalciferol might benefit to hemodialysis patient's muscle strength., Trial Registration: ClinicalTrials.gov NCT04262934 . Registered on 10 February 2020 - Retrospectively registered.

Background: Outpatient procedure in cancer surgery is one of the tracks to guarantee the quality of care respecting the delay of support. The aim of this study was to assess the feasibility and safety of outpatients with axillary lymphadenectomy and the postoperative morbidity after outpatient's procedures compared to patients with classic hospitalization., Methods: Patients who underwent axillary lymphadenectomy for breast cancer or melanoma were analyzed. We selected patients having axillary lymphadenectomy only or associated with another operative act compatible with outpatient's procedure (partial mastectomy, lumpectomy or skin excisions)., Results: Three hundred and forty-nine patients were included. Outpatient procedures were performed in 142 patients (40.7%) and inpatient procedures were performed in 207 patients (59.3%). All time complications combined, we found 148 patients with at least one complication: 77 patients (52.0%) and 71 patients (48.0%) in outpatient and inpatient group, respectively (p=0.0002). The main complication was seroma formation, it concerned 104 patients Among them, Seroma formation was more frequent in ambulatory group, 60 patients (57.7%) and 44 patients (42.3%) in traditional hospitalization (p<0.0001) but 58.7% (61/104) needed only one aspiration and all complications were managed in outpatient., Conclusion: Complications (mostly seroma) appeared usually after hospitalization discharge and they were known and simple to take in charge. A precise preoperative information concerning post-operative morbidity, specially seroma allows a better comprehension and acceptation of this side effect. We believe that this surgery is feasible and safe in outpatient procedure., Competing Interests: Declaration of Competing Interest The authors report no declarations of interest., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

Background: Nipple-sparing mastectomy (NSM) with immediate breast reconstruction (IBR) is used increasingly when performing a prophylactic mastectomy. Few prospective studies have reported on complication rates. This complementary trial to the French prospective multicentre MAPAM trial aimed to evaluate the nipple-areola complex (NAC) necrosis rate in prophylactic NSM with IBR., Methods: Patient characteristics and surgical data were recorded. Morbidity after prophylactic NSM with a focus on NAC necrosis was analysed., Results: Among 59 women undergoing prophylactic NSM, 19 (32 per cent) of the incisions were partly on the NAC. Reconstructions were performed with 46 definitive implants and 13 expanders. The crude rate of postoperative complications was 25 per cent (15 patients). Complete NAC necrosis was reported in two women (3 per cent) and partial or total necrosis in nine (15 per cent). No NAC resection was necessary. Median BMI was lower in women with total or partial NAC necrosis compared with the others (20.0 versus 21.3 kg/m2 respectively; P = 0.034)., Conclusion: Results of this prospective study confirm that prophylactic NSM with IBR is associated with a low risk of total NAC necrosis., (© The Author(s) 2021. Published by Oxford University Press on behalf of BJS Society Ltd. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Diagnosis of atypical breast lesions (ABLs) leads to unnecessary surgery in 75-90% of women. We have previously developed a model including age, complete radiological target excision after biopsy, and focus size that predicts the probability of cancer at surgery. The present study aimed to validate this model in a prospective multicenter setting., - Methods: Women with a recently diagnosed ABL on image-guided biopsy were recruited in 18 centers, before wire-guided localized excisional lumpectomy. Primary outcome was the negative predictive value (NPV) of the model., Results: The NOMAT model could be used in 287 of the 300 patients included (195 with ADH). At surgery, 12 invasive (all grade 1), and 43 in situ carcinomas were identified (all ABL: 55/287, 19%; ADH only: 49/195, 25%). The area under the receiving operating characteristics curve of the model was 0.64 (95% CI 0.58-0.69) for all ABL, and 0.63 for ADH only (95% CI 0.56-0.70). For the pre-specified threshold of 20% predicted probability of cancer, NPV was 82% (77-87%) for all ABL, and 77% (95% CI 71-83%) for patients with ADH. At a 10% threshold, NPV was 89% (84-94%) for all ABL, and 85% (95% CI 78--92%) for the ADH. At this threshold, 58% of the whole ABL population (and 54% of ADH patients) could have avoided surgery with only 2 missed invasive cancers., Conclusion: The NOMAT model could be useful to avoid unnecessary surgery among women with ABL, including for patients with ADH., Clinical Trial Registration: NCT02523612.

Adjuvant systemic treatments in breast cancer are indicated to reduce the risk of relapse. Their systemic side effects have been well documented and include menopausal symptoms such as impaired libido and vaginal dryness, increased risk of endometrial cancer, stroke, musculoskeletal symptoms including arthralgia and myalgia, osteopenia and fractures, skin rashes, and hypercholesterolemia. However, few articles have focused on the oral mucosal reactions related to adjuvant endocrine therapies (AETs) which clearly differ from those reported with chemotherapies or other targeted therapies used for breast cancer. AETs primarily expose patient to a higher risk of worsened periodontal health, salivary flow modifications, taste disturbance, and global deterioration of oral health-related quality of life. Although the rate of permanent discontinuation of AETs because of oral mucosal changes remains low, an interdisciplinary approach to evaluate oral health and to optimize oral supportive care appears essential to ensure an appropriate management and limit dose adjustment in treated patients. In this respect and based on our clinical experience, we propose recommendations to allow oncologists, nurses, and attending practitioners to implement appropriate measures rapidly and/or refer patients to dentists.

Clinical trials involving brain disorders are notoriously difficult to set up and run. Innovative ways to develop effective prevention and treatment strategies for central nervous system (CNS) diseases are urgently needed. New approaches that are likely to renew or at least modify the paradigms used so far have been recently proposed. Quantitative systems pharmacology (QSP) uses mathematical computerized models to characterize biological systems, disease processes and CNS drug pharmacology. Integrated experimental medicine should increase the probability and predictability of success while controlling clinical trials costs. Finally, the societal perspective and patient empowerment also offer additional approaches to demonstrate the benefit of a new drug in the CNS field., (Copyright © 2020. Published by Elsevier Masson SAS.)

We aimed to describe the real-life role of high-flow nasal cannula (HFNC) for bronchiolitis in infants under 3 months of age admitted to three general pediatric departments during the 2017-2018 epidemic period. We retrospectively assessed the clinical severity (Wang score) for every 24-h period of treatment (H0-H24 and H24-H48) according to the initiated medical care (HFNC, oxygen via nasal cannula, or supportive treatments only), the child's discomfort (EDIN score), and transfer to the pediatric intensive care unit (PICU). A total of 138 infants were included: 47±53 days old, 4661±851.9 g, 70 boys (50.7%), 58 with hypoxemia (42%), Wang score of 6.67±2.58, 110 (79.7%) staying for 48 consecutive hours in the same ward. During the H0-H24 period, only patients treated with HFNC had a statistically significant decrease in the severity score (n=21/110; -2 points, P=0.002) and an improvement in the discomfort score (n=15/63; -3.8 points, P<0.0001). There was no difference between groups during the H24-H48 period. The rate of admission to the PICU was 2.9% for patients treated for at least 24 h with HFNC (n=34/138, 44% with oxygen) versus 16.3% for the others (P=0.033). Early use of HFNC improves both clinical status and discomfort in infants younger than 3 months admitted for moderately severe bronchiolitis, whatever their oxygen status., (Copyright © 2020 French Society of Pediatrics. Published by Elsevier Masson SAS. All rights reserved.)

Background: Since the law of February 11, 2005, in France, the number of children with disabilities enrolled in ordinary schools has increased steadily. As a result, the amount of personal support provided by a special needs assistant (personal support) is also increasing. The aim of the study was to describe the diseases and impairments of disabled children aged 2-6, enrolled in mainstream schools and benefiting from personal support for schooling by special needs assistants in the Bouches-du-Rhône (France) in 2014., Methods: A cross-sectional descriptive study was performed. Children included were benefiting from either an individual or shared personal support. Physicians from the territorial organization in charge of disability coded diseases and deficiencies using the International Classification of Diseases, 10th revision, and nomenclature inspired by the International Classification of Functioning, Disability and Health., Results: Medical data were coded for 990 children out of 1260 of the total population. These young disabled children were most frequently children with pervasive developmental disorders (23.3%), lack of expected normal physiological development (19.9%), or mixed specific developmental disorders (13.5%), and most often had behavioral, personality, and relational skills disorders (61.8%), psychomotor function impairments (51.9%), or written or oral language learning impairment (43.2%). Finally, the two main types of impairments most represented among these children were psychological impairments (86.7%) and language and speech impairments (79.8%). The children were most often supported by an individual personal support (for one child only) than by a shared personal support (60% vs. 40%). They were mainly boys (almost 75%)., Conclusion: This study provides working guidelines for the management of health policies relating to disability at the territorial or even national level., (Copyright © 2020 French Society of Pediatrics. Published by Elsevier Masson SAS. All rights reserved.)

Many trials confirmed the safety of omitting axillary dissection in the selected patients treated for early breast cancer. The external validity of these trials is questionable. Our study aimed to evaluate the accuracy of the French population representativity in the SERC trial and the differences between these two populations as well as comparing the French and the Swedish populations (the SENOMIC trial population and the Swedish National Breast Cancer Registry (NKBC) cohort) of patients with sentinel node (SN) micro-metastasis. A higher rate of smaller tumors and grade 1 tumors was observed in the French cohort when compared to the SERC population. Our findings conclude that both French populations show similar characteristics. Positive non-sentinel node (NSN) rates at completion axillary lymph node dissection (ALND) were 10.28 % and 11.3 % in the SERC trial and French cohort, respectively ( p = 0.5). The rate of grade 1 tumors was lower in the SENOMIC trial (16.2%) and in the NKBC cohort (17.4%) compared to the SERC trial population (27.3%) and the French cohort (34.4%). Our findings in addition to the previously demonstrated concordance between the SENOMIC trial and the NKBC populations imply that the results of both the SERC and the SENOMIC trials can be applied to both French and Swedish real populations.

Objective: Systemic sclerosis mainly affects the microvascular network. However, macrovascular manifestations have been reported. We aimed to investigate the characteristics of systemic sclerosis patients with an amputation of a lower limb segment., Methods: We designed a retrospective, case-control, multicentric study on systemic sclerosis patients with amputation of a lower limb segment secondary to critical ischemia via the French Research Group on Systemic Sclerosis. For each case, a control (systemic sclerosis patient without lower limb symptom) was matched with sex, age (±5 years), and cutaneous subset of systemic sclerosis., Results: In total, 26 systemic sclerosis patients (mean age of 67.2 ± 10.9 years, 20 females, 21 limited cutaneous forms) with a lower limb amputation and 26 matched controls (mean age of 67.3 ± 11.2 years, 20 females, 22 limited cutaneous forms) were included. At the time of amputation, the mean disease duration was 12.8 (±8.6) years. In comparison to controls, systemic sclerosis patients with amputation had more digital ulcers (p = 0.048), history of digital ulcers (p = 0.026), and a higher prevalence of pulmonary arterial hypertension (p = 0.024). Systemic sclerosis patients with amputation were more often smokers (p = 0.008) and under corticosteroids (p = 0.015). In the multivariate model, pulmonary arterial hypertension, smoking status, and corticosteroids were independent markers associated with lower limb amputation in systemic sclerosis. In the follow-up, 10 patients (38.5%) had recurrent ischemia requiring a new limb amputation, and five patients (19.2%) had an amputation of the contralateral limb., Conclusion: This study identifies some markers associated with lower limb amputation in systemic sclerosis such as digital ulcers and pulmonary arterial hypertension and points out the high risk associated with tobacco consumption and corticosteroid use., Competing Interests: Declaration of conflicting interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2020.)