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Background: Social Communication Disorder (SCD), introduced in the DSM-5, is distinguished from Autism Spectrum Disorder (ASD) by the absence of restricted and repetitive behaviors or interests (RRBIs)., Aim: To compare the adaptive, sensory, communication, and cognitive profiles of children with ASD and SCD., Methods: The assessments of nine children with SCD and ten with ASD were compared with either Fisher's Exact Test or the Mann-Whitney Test. Assessments included the Vineland Adaptive Behavior Scales, the Autism Diagnostic Observation Schedule (ADOS), the Short Sensory Profile, Bishop's Children's Communication Checklist, a pragmatics evaluation, and the Wechsler Intelligence Scale for Children IV., Results: The total ADOS score and the second subtotal "Restricted and Repetitive Behaviors" were significantly higher ( p = 0.022) in the ASD group than in the SCD group. The Vineland standard score for the "Socialization" domain was significantly lower ( p = 0.037) in the ASD group (mean: 51 +/- 19) than in the SCD group (mean: 80 +/- 28). The working memory index score was also significantly lower ( p = 0.013) in the ASD group compared to the SCD group., Conclusions: While ASD and SCD share similarities in communication and pragmatic difficulties, some distinctions have been identified, e.g. in executive functioning and the impact on socialization, which may be linked to the absence of RRBIs in SCD. These findings highlight the challenges posed by this nosographic separation during diagnostic evaluations due to the scarcity of discriminative tools.

Background: Despite early diagnosis, approximately 20% of patients with ER-positive and HER2-negative breast cancer (BC) will experience disease recurrence. Improved survival has been reported with adjuvant treatment combining cyclin-dependent kinase 4/6 inhibitors with endocrine therapy, in high-risk patients with ER-positive and HER2-negative BC, regardless of age. Older patients have higher rates of ER-positive/HER2-negative BC than younger patients. Methods: In this real-world data analysis, MonarchE and NataLEE high-risk patients accounted for 9.5% and 33% of patients undergoing upfront surgery, respectively. Significantly higher eligibility rates were observed in patients who underwent a mastectomy, >70 years and ≤40 years for adjuvant abemaciclib and ribociclib, and in patients >80 years for ribociclib. Results: Eligibility rates in patients ≤40 years and >80 years who underwent mastectomy were 27.8% and 24.7% for abemaciclib, respectively, and 56.6% and 65.2% for ribociclib, respectively. A higher discontinuation rate for abemaciclib was reported in patients aged ≥65 years and it can be assumed that discontinuation rates may increase in even older patients. Conclusions: If the results of the NataLEE trial translate into clinical practice, the number of patients potentially eligible for adjuvant CDK4/6 inhibitors may increase, especially in the elderly population.

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.

Background: Methylphenidate is indicated for attention deficit hyperactivity disorder (ADHD). Several studies have evaluated its abuse in specific populations (students, drug users) and few in the general population. This work describes the extent of its abuse in a region of more than 5 million inhabitants., Method: Based on regional health insurance data from 2005 to 2017, the clustering method identifies different methylphenidate use profiles according to several characteristics (number of different prescribers and pharmacies, number of dispensations, number of defined daily dose dispensed). The groups characterised by high values of these variables will be qualified as "deviant"., Results: In 13 years, the number of patients with at least one dispensation in the first quarter has been multiplied by 5.8 times. The proportion of adults has increased (20% in 2017) and their number has been multiplied by 10. Five groups are identified, three of them are characterised by "deviant" behaviour. Group 5 (n=11, 0.04%) has higher values than 4 (n=112, 0.4%) and 3 (n=407, 1.6%). These patients are older and more frequently use benzodiazepines and opiate substitution drugs. Groups 1 (n=13,132, 51%) and 2 (n=11,941, 46.7%) are more likely to be taken up by young subjects. The number of subjects with "deviant" behaviour increased until 2011 and after a decrease, the highest number of subjects concerned has been observed since 2015., Conclusion: In view of the increase of subjects with "deviant" behaviour, it is necessary to make the medical community and patients aware on the risk of abuse of methylphenidate. The recent extension of the indication for ADHD in adults and the broadening of the conditions of prescription require increased vigilance., (Copyright © 2022 Société française de pharmacologie et de thérapeutique. Published by Elsevier Masson SAS. All rights reserved.)

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).)