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Background: The main aim of this study was to analyse the 6-month survival rates in peri-acetabular metastasis patients undergoing total hip arthroplasty (THA) with an acetabular cage and without curettage. The secondary objectives were to analyse the global survival rates, the factors influencing patient survival and to evaluate mechanical complication rates after THA. Methods: This study was carried out on a cohort of 93 consecutive patients who underwent THA with an acetabular cage without curettage for acetabular metastasis or multiple myeloma lesions between 2010 and 2020. The National Death Registry was consulted to obtain the exact date of death of the patients; the minimum follow-up time was 2 years. Results: The 6-month survival rate for all types of cancer was 78 % [68 – 85], the 1-year survival rate was 66 % [55 – 74], and the 5-year survival rate was 26 % [17 – 36]. The median overall survival for the cohort was 24.37 months [16.10 – 32.63]. The mean overall survival was 46.02 months [32.89 – 59.16]. At last contact, 86 % of the operated patients were walking again.No patient died from surgery. The ECOG performance status score, the number of bone metastatic sites, the presence of visceral metastases and the number of lines of systemic therapy undertaken prior to surgery were negative survival factors. Three patients (3.2 %) had early prosthetic dislocation, 2 patients (2.2 %) showed aseptic loosening of her partial hip implant after 10 and 11 years respectively and 4 patients (4.3 %) had an early infection treated by debridement, antibiotics and implant retention to control the infection. During the follow-up period, no new femoral metastases were detected in any patient. Conclusion: Surgery without curettage is an effective treatment for periacetabular metastasis. It gives reliable results, regardless of the type of acetabular lesion, allowing most patients to walk again and does not modify the patient’s survival.

Background: Cervical dystonia is widely understood to benefit from botulinum toxin injections. The injection practices may be influenced by specific factors, including the method of injection. Three main guidance methods can be used: palpation of anatomical landmarks, ultrasound, and electromyography. We investigated how target muscles and doses of botulinum toxin were modified after the transition from surface anatomy (non-guided) to ultrasound (US-guided), in patients with cervical dystonia. We also determined the long-term dose trend. Methods: We studied a group of 82 patients, who received non-guided injections (median: 16.5 cycles/5.1 years) followed by US-guided injections (median: 12.0 cycles/3.8 years). Results: More muscles, and especially deep muscles, were injected during the US-guided period. The total dose and number of injected muscles were higher when US guidance was used, but the mean dose per muscle was lower. Over the long term, the total dose stabilized, and the mean dose per muscle decreased during the US-guided period. Conclusions: According to our results, the guidance method has a strong impact on the botulinum toxin injection strategy in cervical dystonia (target muscles and dose). Also, the treatment appeared more stable when using US guidance; this could be explained by the good precision of such injections.

Abstract Background Ventilator-associated pneumonia (VAP) is common in patients with severe SARS-CoV-2 pneumonia. The aim of this ancillary analysis of the coVAPid multicenter observational retrospective study is to assess the relationship between adjuvant corticosteroid use and the incidence of VAP. Methods Planned ancillary analysis of a multicenter retrospective European cohort in 36 ICUs. Adult patients receiving invasive mechanical ventilation for more than 48 h for SARS-CoV-2 pneumonia were consecutively included between February and May 2020. VAP diagnosis required strict definition with clinical, radiological and quantitative microbiological confirmation. We assessed the association of VAP with corticosteroid treatment using univariate and multivariate cause-specific Cox’s proportional hazard models with adjustment on pre-specified confounders. Results Among the 545 included patients, 191 (35%) received corticosteroids. The proportional hazard assumption for the effect of corticosteroids on the incidence of VAP could not be accepted, indicating that this effect varied during ICU stay. We found a non-significant lower risk of VAP for corticosteroid-treated patients during the first days in the ICU and an increased risk for longer ICU stay. By modeling the effect of corticosteroids with time-dependent coefficients, the association between corticosteroids and the incidence of VAP was not significant (overall effect p = 0.082), with time-dependent hazard ratios (95% confidence interval) of 0.47 (0.17–1.31) at day 2, 0.95 (0.63–1.42) at day 7, 1.48 (1.01–2.16) at day 14 and 1.94 (1.09–3.46) at day 21. Conclusions No significant association was found between adjuvant corticosteroid treatment and the incidence of VAP, although a time-varying effect of corticosteroids was identified along the 28-day follow-up.

Pagneux et al. developed a nanobody-functionalized electrochemical platform with smartphone readout to detect SARS-CoV-2 in clinical samples. They demonstrated that their device can rapidly and accurately detect SARS-CoV-2 in saliva and nasopharyngeal swab samples and discriminate between this virus and other respiratory viruses.

Abstract Objectives In children, achieving an acceptable degree of accuracy from dietary or physical activity (PA) assessments remains a challenge. Children tend to overestimate their time spent in daily PA and underestimate their dietary intake of fat and sugar. Because parents play a key role in family lifestyle decisions, including children’s food choices and PA levels, it is important to investigate the responses of parents regarding their children’s lifestyle habits. We aimed to develop a Self-Administered Parental Assessment of Children’s Lifestyle (SAPLACL) questionnaire and test its feasibility and reliability in 191 parents (29 fathers and 162 mothers). Results For each part of the questionnaire, the rate of missing or improper responses ranged from 0 to 24%. The highest proportion of problems in understanding was reported for the dietary intake dimension, especially for snacking in front of the TV. Some difficulty was also found regarding the question on leisure PA. Test–retest agreement was observed in 54.7–100% of the respondents. Overall, the kappa coefficients were favorable. Thus, the parent self-report questionnaire is a valid and accurate tool for analyzing children’s lifestyle habits in France.

Abstract Background Recent multicenter studies identified COVID-19 as a risk factor for invasive pulmonary aspergillosis (IPA). However, no large multicenter study has compared the incidence of IPA between COVID-19 and influenza patients. Objectives To determine the incidence of putative IPA in critically ill SARS-CoV-2 patients, compared with influenza patients. Methods This study was a planned ancillary analysis of the coVAPid multicenter retrospective European cohort. Consecutive adult patients requiring invasive mechanical ventilation for > 48 h for SARS-CoV-2 pneumonia or influenza pneumonia were included. The 28-day cumulative incidence of putative IPA, based on Blot definition, was the primary outcome. IPA incidence was estimated using the Kalbfleisch and Prentice method, considering extubation (dead or alive) within 28 days as competing event. Results A total of 1047 patients were included (566 in the SARS-CoV-2 group and 481 in the influenza group). The incidence of putative IPA was lower in SARS-CoV-2 pneumonia group (14, 2.5%) than in influenza pneumonia group (29, 6%), adjusted cause-specific hazard ratio (cHR) 3.29 (95% CI 1.53–7.02, p = 0.0006). When putative IPA and Aspergillus respiratory tract colonization were combined, the incidence was also significantly lower in the SARS-CoV-2 group, as compared to influenza group (4.1% vs. 10.2%), adjusted cHR 3.21 (95% CI 1.88–5.46, p

Cervical cancer screening (CCS) by Pap tests is mainly performed by gynecologists in France, but also by general practitioners (GPs) and midwives. The screening uptake is insufficient to reduce the incidence of cervical neoplasms. Our aim was to investigate the association between screening rates in patients listed with GPs and the distance between GPs' offices and gynecology facilities. The population of 345 GPs, and their 93,918 female patients eligible for screening over 3 years (2013–2015), were derived from the Health Insurance claim database. We estimated the socioeconomic level of the geographical area of GPs' offices using the European Deprivation Index (EDI). The proximity of gynecology facilities was calculated by computing their distance from GPs' offices (in order to adjust the proximity of gynecology facilities with EDI and performance of smears by the GP). The number of gynecologists within 5 km of a GP's office was associated with the CCS rate increasing by 0.31% for every unit increase in the density of gynecologists within 5 km (p < 0.0001). The close proximity of gynecology facilities was not significantly associated with screening uptake among female patients when the office of the GP where they were registered was settled in a deprived area.

Abstract Background In many clinical applications, evolution of a longitudinal marker is censored by an event occurrence, and, symmetrically, event occurrence can be influenced by the longitudinal marker evolution. In such frameworks joint modeling is of high interest. The Joint Latent Class Model (JLCM) allows to stratify the population into groups (classes) of patients that are homogeneous both with respect to the evolution of a longitudinal marker and to the occurrence of an event; this model is widely employed in real-life applications. However, the finite sample-size properties of this model remain poorly explored. Methods In the present paper, a simulation study is carried out to assess the impact of the number of individuals, of the censoring rate and of the degree of class separation on the finite sample size properties of the JLCM. A real-life application from the neurology domain is also presented. This study assesses the precision of class membership prediction and the impact of covariates omission on the model parameter estimates. Results Simulation study reveals some departures from normality of the model for survival sub-model parameters. The censoring rate and the number of individuals impact the relative bias of parameters, especially when the classes are weakly distinguished. In real-data application the observed heterogeneity on individual profiles in terms of a longitudinal marker evolution and of the event occurrence remains after adjusting to clinically relevant and available covariates; Conclusion The JLCM properties have been evaluated. We have illustrated the discovery in practice and highlights the usefulness of the joint models with latent classes in this kind of data even with pre-specified factors. We made some recommendations for the use of this model and for future research.

IntroductionSoluble markers of B cell activation are interesting diagnostic and prognostic tools in autoimmune diseases. Data in systemic sclerosis (SSc) are scarce and few studies focused on their association with disease characteristics.Methods1. Serum levels of 14 B cell biomarkers (β2-microglobulin, rheumatoid factor (RF), immunoglobulins (Ig) G, IgA, IgM, BAFF, APRIL, soluble (s)TACI, sBCMA sCD21, sCD23, sCD25, sCD27, CXCL13) were measured in SSc patients and healthy controls (HC). 2. Associations between these biomarkers and SSc characteristics were assessed. 3. The pathophysiological relevance of identified associations was explored by studying protein production in B cell culture supernatant.ResultsIn a discovery panel of 80 SSc patients encompassing the broad spectrum of disease manifestations, we observed a higher frequency of RF positivity, and increased levels of β2-microglobulin, IgG and CXCL13 compared with HC. We found significant associations between several biomarkers and SSc characteristics related to disease phenotype, activity and severity. Especially, serum IgG levels were associated with pulmonary hypertension (PH); β2-microglobulin with Nt-pro-BNP and DLCO; and BAFF with peak tricuspid regurgitation velocity (TRV). In a validation cohort of limited cutaneous SSc patients without extensive ILD, we observed lower serum IgG levels, and higher β2-microglobulin, sBCMA, sCD23 and sCD27 levels in patients with pulmonary arterial hypertension (PAH). BAFF levels strongly correlated with Nt-pro-BNP levels, FVC/DLCO ratio and peak TRV in SSc-PAH patients. Cultured SSc B cells showed increased production of various angiogenic factors (angiogenin, angiopoietin-1, VEGFR-1, PDGF-AA, MMP-8, TIMP-1, L-selectin) and decreased production of angiopoietin-2 compared to HC.ConclusionSoluble markers of B cell activation could be relevant tools to assess organ involvements, activity and severity in SSc. Their associations with PAH could plead for a role of B cell activation in the pathogenesis of pulmonary microangiopathy. B cells may contribute to SSc vasculopathy through production of angiogenic mediators.

Abstract Background Patients with SARS-CoV-2 infection are at higher risk for ventilator-associated pneumonia (VAP). No study has evaluated the relationship between VAP and mortality in this population, or compared this relationship between SARS-CoV-2 patients and other populations. The main objective of our study was to determine the relationship between VAP and mortality in SARS-CoV-2 patients. Methods Planned ancillary analysis of a multicenter retrospective European cohort. VAP was diagnosed using clinical, radiological and quantitative microbiological criteria. Univariable and multivariable marginal Cox’s regression models, with cause-specific hazard for duration of mechanical ventilation and ICU stay, were used to compare outcomes between study groups. Extubation, and ICU discharge alive were considered as events of interest, and mortality as competing event. Findings Of 1576 included patients, 568 were SARS-CoV-2 pneumonia, 482 influenza pneumonia, and 526 no evidence of viral infection at ICU admission. VAP was associated with significantly higher risk for 28-day mortality in SARS-CoV-2 (adjusted HR 1.70 (95% CI 1.16–2.47), p = 0.006), and influenza groups (1.75 (1.03–3.02), p = 0.045), but not in the no viral infection group (1.07 (0.64–1.78), p = 0.79). VAP was associated with significantly longer duration of mechanical ventilation in the SARS-CoV-2 group, but not in the influenza or no viral infection groups. VAP was associated with significantly longer duration of ICU stay in the 3 study groups. No significant difference was found in heterogeneity of outcomes related to VAP between the 3 groups, suggesting that the impact of VAP on mortality was not different between study groups. Interpretation VAP was associated with significantly increased 28-day mortality rate in SARS-CoV-2 patients. However, SARS-CoV-2 pneumonia, as compared to influenza pneumonia or no viral infection, did not significantly modify the relationship between VAP and 28-day mortality. Clinical trial registration The study was registered at ClinicalTrials.gov, number NCT04359693.

Summary: Background: The present study aimed to evaluate the persistent immunogenicity offered by a third dose of BNT162b2 against Delta and Omicron variants, in nursing home (NH) residents. Methods: In this monocenter prospective observational study, anti-spike IgG levels, S1 domain reactive T cell counts, serum neutralizing antibody titers against Delta and Omicron variants were compared before and up to three months after the BNT162b2 booster dose, in NH residents without COVID-19 (COVID-19 naive) or with COVID-19 prior to initial vaccination (COVID-19 recovered). Findings: 106 NH residents (median [interquartile range] age: 86·5 [81;91] years) were included. The booster dose induced a high increase of anti-spike antibody levels in all subjects (p

Abstract Background Pre-pregnancy obesity and excessive gestational weight gain (GWG) are established risk factors for adverse pregnancy, delivery and birth outcomes. Pregnancy is an ideal moment for nutritional interventions in order to establish healthier lifestyle behaviors in women at high risk of obstetric and neonatal complications. Methods Electronic-Personalized Program for Obesity during Pregnancy to Improve Delivery (ePPOP-ID) is an open multicenter randomized controlled trial which will assess the efficacy of an e-health web-based platform offering a personalized lifestyle program to obese pregnant women in order to reduce the rate of labor procedures and delivery interventions in comparison to standard care. A total of 860 eligible pregnant women will be recruited in 18 centers in France between 12 and 22 weeks of gestation, randomized into the intervention or the control arm and followed until 10 weeks of postpartum. The intervention is based on nutrition, eating behavior, physical activity, motivation and well-being advices in which personalization is central, as well as the use of a mobile/tablet application. Inputs includes data from the medical record of participants (medical history, anthropometric data), from the web platform (questionnaires on dietary habits, eating behavior, physical activity and motivation in both groups), and adherence to the program (time of connection for the intervention group only). Data are collected at inclusion, 32 weeks, delivery and 10 weeks postpartum. As primary outcome, we will use a composite endpoint score of obstetrical interventions during labor and delivery, defined as caesarean section and instrumental delivery (forceps and vacuum extractor). Secondary outcomes will consist of data routinely collected as part of usual antenatal and perinatal care, such as GWG, hypertension, preeclampsia, as well as fetal and neonatal outcomes including premature birth, gestational age at birth, birth weight, macrosomia, Apgar score, arterial umbilical cord pH, neonatal traumatism, hyperbilirubinemia, respiratory distress syndrome, transfer in neonatal intensive care unit, and neonatal adiposity. Post-natal outcomes will be duration of breastfeeding, maternal weight retention and child weight at postnatal visit. Discussion The findings of the ePPOP-ID trial will help design e-health intervention program for obese women in pregnancy. Trial registration ClinicalTrials.gov Identifier: NCT02924636 / October 5th 2016.

Abstract Background Usability testing of medical devices are mandatory for market access. The testings’ goal is to identify usability problems that could cause harm to the user or limit the device’s effectiveness. In practice, human factor engineers study participants under actual conditions of use and list the problems encountered. This results in a binary discovery matrix in which each row corresponds to a participant, and each column corresponds to a usability problem. One of the main challenges in usability testing is estimating the total number of problems, in order to assess the completeness of the discovery process. Today’s margin-based methods fit the column sums to a binomial model of problem detection. However, the discovery matrix actually observed is truncated because of undiscovered problems, which corresponds to fitting the marginal sums without the zeros. Margin-based methods fail to overcome the bias related to truncation of the matrix. The objective of the present study was to develop and test a matrix-based method for estimating the total number of usability problems. Methods The matrix-based model was based on the full discovery matrix (including unobserved columns) and not solely on a summary of the data (e.g. the margins). This model also circumvents a drawback of margin-based methods by simultaneously estimating the model’s parameters and the total number of problems. Furthermore, the matrix-based method takes account of a heterogeneous probability of detection, which reflects a real-life setting. As suggested in the usability literature, we assumed that the probability of detection had a logit-normal distribution. Results We assessed the matrix-based method’s performance in a range of settings reflecting real-life usability testing and with heterogeneous probabilities of problem detection. In our simulations, the matrix-based method improved the estimation of the number of problems (in terms of bias, consistency, and coverage probability) in a wide range of settings. We also applied our method to five real datasets from usability testing. Conclusions Estimation models (and particularly matrix-based models) are of value in estimating and monitoring the detection process during usability testing. Matrix-based models have a solid mathematical grounding and, with a view to facilitating the decision-making process for both regulators and device manufacturers, should be incorporated into current standards.

Abstract Background Differentiating Ventilator-Associated Tracheobronchitis (VAT) from Ventilator-Associated Pneumonia (VAP) may be challenging for clinicians, yet their management currently differs. In this study, we evaluated the accuracy of the Clinical Pulmonary Infection Score (CPIS) to differentiate VAT and VAP. Methods We performed a retrospective analysis based on the data from 2 independent prospective cohorts. Patients of the TAVeM database with a diagnosis of VAT (n = 320) or VAP (n = 369) were included in the derivation cohort. Patients admitted to the Intensive Care Centre of Lille University Hospital between January 1, 2016 and December 31, 2017 who had a diagnosis of VAT (n = 70) or VAP (n = 139) were included in the validation cohort. The accuracy of the CPIS to differentiate VAT from VAP was assessed within the 2 cohorts by calculating sensitivity and specificity values, establishing the ROC curves and choosing the best threshold according to the Youden index. Results The areas under ROC curves of CPIS to differentiate VAT from VAP were calculated at 0.76 (95% CI [0.72–0.79]) in the derivation cohort and 0.67 (95% CI [0.6–0.75]) in the validation cohort. A CPIS value ≥ 7 was associated with the highest Youden index in both cohorts. With this cut-off, sensitivity and specificity were respectively found at 0.51 and 0.88 in the derivation cohort, and at 0.45 and 0.89 in the validation cohort. Conclusions A CPIS value ≥ 7 reproducibly allowed to differentiate VAT from VAP with high specificity and PPV and moderate sensitivity and NPV in our derivation and validation cohorts.

Abstract Background Postoperative upper gastrointestinal fistula (PUGIF) is a devastating complication, leading to high mortality (reaching up to 80%), increased length of hospital stay, reduced health-related quality of life and increased health costs. Nutritional support is a key component of therapy in such cases, which is related to the high prevalence of malnutrition. In the prophylactic setting, enteral nutrition (EN) is associated with a shorter hospital stay, a lower incidence of severe infectious complications, lower severity of complications and decreased cost compared to total parenteral nutrition (TPN) following major upper gastrointestinal (GI) surgery. There is little evidence available for the curative setting after fistula occurrence. We hypothesize that EN increases the 30-day fistula closure rate in PUGIF, allowing better health-related quality of life without increasing the morbidity or mortality. Methods/design The NUTRILEAK trial is a multicenter, randomized, parallel-group, open-label phase III trial to assess the efficacy of EN (the experimental group) compared with TPN (the control group) in patients with PUGIF. The primary objective of the study is to compare EN versus TPN in the treatment of PUGIF (after esophagogastric resection including bariatric surgery, duodenojejunal resection or pancreatic resection with digestive tract violation) in terms of the 30-day fistula closure rate. Secondary objectives are to evaluate the 6-month postrandomization fistula closure rate, time of first fistula closure (in days), the medical- and surgical treatment-related complication rate at 6 months after randomization, the fistula-related complication rate at 6 months after randomization, the type and severity of early (30 days after randomization) and late fistula-related complications (over 30 days after randomization), 30-day and 6-month postrandomization mortality rate, nutritional status at day 30, day 60, day 90 and day 180 postrandomization, the mean length of hospital stay, the patient’s health-related quality of life (by self-assessment questionnaire), oral feeding time and direct costs of treatment. A total of 321 patients will be enrolled. Discussion The two nutritional supports are already used in daily practice, but most surgeons are reluctant to use the enteral route in case of PUGIF. This study will be the first randomized trial testing the role of EN versus TPN in PUGIF. Trial registration ClinicalTrials.gov: NCT03742752 . Registered on 14 November 2018.

Abstract Background Systemic sclerosis (SSc) is a severe and highly heterogeneous disease. The modified Rodnan skin score (mRSS) is a widely used tool for the assessment of the extent and degree of skin thickness. This study aimed to identify the classes of patients with early similar skin thickening trajectories without any a priori assumptions and study their associations with organ involvement and survival. Methods From the French SSc national cohort, patients with a disease duration of less than 2 years at inclusion and with at least 2 mRSS available within the first 4 years of follow-up were enrolled. Classes of patients with similar mRSS trajectories were identified based on a latent class mixed model. The clinical characteristics and survival rate were compared between the obtained classes. Results A total of 198 patients fulfilled the inclusion criteria, with a total of 641 mRSS available. The median disease duration and follow-up were 0.8 (interquartile range 0.4; 1.2) and 6.3 (3.8; 8.9) years, respectively. Individual trajectories of mRSS were highly heterogeneous between patients. Models with 1–6 latent classes of trajectories were sequentially assessed, and the 5-class model represented the best fit to data. Each class was characterized by a unique global trajectory of mRSS. The median disease duration did not differ significantly between classes. Baseline organ involvement was more frequent in classes with significant change over time (classes 2–5) than in class 1 (low baseline mRSS without significant change over time). Using Cox regression, we observed a progressively increasing risk of death from classes 1 to 5. Conclusions Early identification of clinical phenotype based on skin thickening trajectories could predict morbi-mortality in SSc. This study suggested that mRSS trajectories characterization might be pivotal for clinical practice and future trial designs.

Long-term care facility (LTCF) older residents display physiological alterations of cellular and humoral immunity that affect vaccine responses. Preliminary reports suggested a low early postvaccination antibody response against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The aim of this study was to focus on the specific T-cell response. We quantified S1-specific IgG, neutralizing antibody titers, total specific IFNγ-secreting T cells by ELISpot, and functionality of CD4+- and CD8+-specific T cells by flow cytometry, after two doses of the BNT162b2 vaccine in younger and older people, with and without previous COVID-19 infection (hereafter referred to as COVID-19-recovered and COVID-19-naive subjects, respectively). Frailty, nutritional, and immunosenescence parameters were collected at baseline in COVID-19-naive older people. We analyzed the immune response in 129 young adults (median age 44.0 years) and 105 older residents living in a LCTF (median age 86.5 years), 3 months after the first injection. Humoral and cellular memory responses were dramatically impaired in the COVID-19-naive older (n = 54) compared with the COVID-19-naive younger adults (n = 121). Notably, older participants’ neutralizing antibodies were 10 times lower than the younger’s antibody titers (p

Abstract Background Clinical data identified an association between the use of HMG-CoA reductase inhibitors (statins) and incident diabetes in patients with underlying diabetes risk factors such as obesity, hypertension and dyslipidemia. The molecular mechanisms however are unknown. Methods An observational cross-sectional study included 910 severely obese patients, mean (SD) body mass index (BMI) 46.7 (8.7), treated with or without statins (ABOS cohort: a biological atlas of severe obesity). Data and sample collection took place in France between 2006 and 2016. Transcriptomic signatures of statin treatment in human liver obtained from genome-wide transcriptomic profiling of five different statin drugs using microarrays were correlated to clinico-biological phenotypes and also assigned to biological pathways and mechanisms. Patients from the non-statin-users group were matched to patients in the statin users group by propensity score analysis to minimize confounding effects from age, gender, parental familial history of diabetes, BMI, waist circumference, systolic and diastolic blood pressure and use of anti-hypertensive drugs as pre-specified covariates. Results We determined the hepatic, statin-related gene signature from genome-wide transcriptomic profiling in severely obese patients with varying degrees of glucose tolerance and cardio-metabolic comorbidities. One hundred and fifty seven patients on statin treatment in the matched cohort showed higher diabetes prevalence (OR = 2.67; 95%CI, 1.60–4.45; P = 0.0002) and impairment of glucose homeostasis. This phenotype was associated with molecular signatures of increased hepatic de novo lipogenesis (DNL) via activation of sterol regulatory element-binding protein 1 (SREBP1) and concomitant upregulation of the expression of key genes in both fatty acid and triglyceride metabolism. Conclusions A DNL gene activation profile in response to statins is associated with insulin resistance and the diabetic status of the patients. Identified molecular signatures thus suggest that statin treatment increases the risk for diabetes in humans at least in part via induction of DNL. Trial registration NCT01129297. Registered May 242,010 (retrospectively registered).

Abstract Background Catheter-related bacteremia (CRB) is the most frequent nosocomial infection in neonatal intensive care unit (NICU) patients, especially in very low-birth-weight infants. Administration of injectable drugs in premature newborn infants has many particularities and several types of infusion incidents have been reported. The Edelvaiss® Multiline NEO device is a novel multi-lumen access infusion device adapted to the specificities of infusion in neonatology. This multicenter, randomized, controlled study was therefore designed to determine whether or not Edelvaiss® Multiline NEO reduces the risk of CRB in preterm newborn infants in an NICU. Methods/design This is a multicenter, randomized, controlled trial, using a cluster-randomized crossover design. Four investigator centers (four clusters) will participate in the study and will be randomized into two groups, corresponding to two different sequences (either the Edelvaiss® Multiline NEO or standard infusion system sequence, then vice versa). A total of 280 patients will be recruited. Infants will be enrolled in the study at the time of placing a single-lumen central venous catheter. Three visits recording specific data are planned in the study protocol. The primary outcome measure is the incidence density (ID) of CRB. For each patient, the total number of catheters and CRB incidents as well as the duration of stay in the NICU will be computed and considered for analysis. Discussion The study will provide high-quality evidence to determine whether the Multiline NEO device reduces the risk of CRB in preterm newborns in NICUs or not. Trial registration ClinicalTrials.gov, NCT02633124. Registered on 7 December 2015.

Background: French (2014) and American (2017) pediatric guidelines recommend starting enteral nutrition (EN) early in pediatric intensive care. The aims of this study were to compare the applicability of the guidelines in the pediatric intensive care unit (PICU) and to identify risk factors of non-application of the guidelines.Methods: This retrospective, single-center study was conducted in a medical–surgical PICU between 2014 and 2016. All patients from 1 month to 18 years old with a length of stay >48 h and an exclusive EN at least 1 day during the PICU stay were included. The outcome variable was application of the 2014 and 2017 guidelines, defined by energy intakes ≥90% of the recommended intake at least 1 day as defined by both guidelines. The risk factors of non-application were studied comparing “optimal EN” vs. “non-optimal EN” groups for both guidelines.Results: In total, 416 children were included (mortality rate, 8%). Malnutrition occurred in 36% of cases. The mean energy intake was 34 ± 30.3 kcal kg−1 day−1. The 2014 and 2017 guidelines were applied in 183 (44%) and 296 (71%) patients, respectively (p < 0.05). Following the 2017 guidelines, enteral energy intakes were considered as “satisfactory enteral intake” for 335 patients (81%). Hemodynamic failure was a risk factor of the non-application of both guidelines.Conclusion: In our PICU, the received energy intake approached the level of intake recommended by the American 2017 guidelines, which used the predictive Schofield equations and seem more useful and applicable than the higher recommendations of the 2014 guidelines. Multicenter studies to validate the pediatric guidelines seem necessary.

Background: Surgery is the primary treatment for basal cell carcinoma (BCC). In locally advanced basal cell carcinoma (laBCC), surgery may cause functional or aesthetic damage. In laBCC, neoadjuvant administration of vismodegib, an inhibitor of the Hedgehog signaling pathway, may reduce tumor size, facilitate resection, and reduce functional and aesthetic consequences of surgery. The VISMONEO study assessed efficacy and safety of vismodegib in neoadjuvant treatment of laBCC. Methods: VISMONEO (NCT02667574) is an open-label, noncomparative, multicenter, phase 2 study. Patients with ≥1 histologically confirmed facial BCC, inoperable or operable with functional or major aesthetic sequelae risk, were included. Oral vismodegib 150 mg was administered once daily for 4 to 10 months before planned surgery, which was performed once the best response under vismodegib was observed. Primary endpoint was percentage of patients with BCC with tumor downstaging following surgical resection after neoadjuvant vismodegib. Downstaging was defined according to a 6-stage surgical classification related to the aesthetic and functional consequences of surgery. Findings: 55 patients (median age: 73 years) with laBCC were included from November 2014 to June 2015. At inclusion, 4 patients were inoperable, 15 were operable with a major functional risk, and 36 were operable with a minor functional risk or a major aesthetic risk. Mean size of target lesion was 47.3 mm (SD: 27.2 mm). 44 patients presented with downstaging after vismodegib treatment (80%; 95% confidence interval [CI], 67 to 90). Of these 44 patients, 27 had a complete response (25 proved by biopsy). Mean treatment duration was 6.0 months. Overall Response Rate according to RECIST 1.1 criteria was 71% (95% CI, 59 to 88). At 3-years of follow-up, 16/44 patients had known recurrence (36%; 95%CI, 22 to 51). Interpretation: Neoadjuvant vismodegib allows for a downstaging of the surgical procedure for laBCCs in functionally sensitive locations. Funding: VISMONEO was funded by F. Hoffmann-La Roche Ltd.

Background: During COVID-19, the main manifestations of the disease are not only pneumonia but also coagulation disorders. The purpose of this study was to evaluate pulmonary vascular abnormalities 3 months after hospitalization for SARS-CoV-2 pneumonia in patients with persistent respiratory symptoms. Methods: Among the 320 patients who participated in a systematic follow-up 3 months after hospitalization, 76 patients had residual symptoms justifying a specialized follow-up in the department of pulmonology. Among them, dual-energy CT angiography (DECTA) was obtained in 55 patients. Findings: The 55 patients had partial (n = 40; 72.7%) or complete (n = 15; 27.3%) resolution of COVID-19 lung infiltration. DECTA was normal in 52 patients (52/55; 94.6%) and showed endoluminal filling defects in 3 patients (3/55; 5.4%) at the level of one (n = 1) and two (n = 1) segmental arteries of a single lobe and within central and peripheral arteries (n = 1). DECT lung perfusion was rated as non-interpretable (n = 2;3.6%), normal (n = 17; 30.9%) and abnormal (n = 36; 65.5%), the latter group comprising 32 patients with residual COVID-19 opacities (32/36; 89%) and 4 patients with normal lung parenchyma (4/36; 11%). Perfusion abnormalities consisted of (a) patchy defects (30/36; 83%), (b) PE-type defects (6/36; 16.6%) with (n = 1) or without proximal thrombosis (n = 5); and (c) focal areas of hypoperfusion (2/36; 5.5%). Increased perfusion was seen in 15 patients, always matching GGOs, bands and/or vascular tree-in- bud patterns. Interpretation: DECT depicted proximal arterial thrombosis in 5.4% of patients and perfusion abnormalities suggestive of widespread microangiopathy in 65.5% of patients. Lung microcirculation was abnormal in 4 patients with normal lung parenchyma.

Background Ultrasound (US) guidance provides the unique opportunity to control the puncture zone of the artery during transfemoral transcatheter aortic valve replacement and may decrease major vascular complications (VC) and life‐threatening or major bleeding complications. This study aimed to evaluate the clinical impact of US guidance using a propensity score–matched comparison. Methods and Results US guidance was implemented as the default approach for all transfemoral transcatheter aortic valve replacement cases in our institution in June 2013. We defined 3 groups of consecutive patients according to the method of puncture (fluoroscopic/US guidance) and the use of a transcatheter heart valve. Patients in the US‐guided second‐generation group (Sapien XT [Edwards Lifesciences, Irvine, CA], Corevalve [Medtronic, Dublin, Ireland]) were successfully 1:1 matched with patients in the fluoroscope‐guided second‐generation group (n=95) with propensity score matching. In a second analysis we described the consecutive patients of the US‐guided third‐generation group (Evolut‐R [Medtronic], Sapien 3 [Edwards Lifesciences], n=308). All vascular and bleeding complications were reduced in the US‐guided second‐generation group compared with the fluoroscope‐guided second‐generation group: VC (16.8% versus 6.3%; P=0.023); life‐threatening or major bleeding (22.1% versus 6%; P=0.004); and VC related to vascular access (12.6% versus 4.2%; P=0.052). In the US‐guided third‐generation group the rates of major VC and life‐threatening or major bleeding were 3.2% (95% CI, 1.6% to 5.9%) and 3.6% (95% CI, 1.8% to 6.3%). In the overall population (n=546), life‐threatening or major bleeding was associated with a 1.7‐fold increased mortality risk (P=0.02). Conclusions We demonstrated that US guidance effectively reduced VC and bleeding complications for transfemoral transcatheter aortic valve replacement and should be considered the standard puncture method. Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT02628509.

Abstract Objectives Assessment of the adaptive immune response against severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) is crucial for studying long‐term immunity and vaccine strategies. We quantified IFNγ‐secreting T cells reactive against the main viral SARS‐CoV‐2 antigens using a standardised enzyme‐linked immunospot assay (ELISpot). Methods Overlapping peptide pools built from the sequences of M, N and S viral proteins and a mix (MNS) were used as antigens. Using IFNγ T‐CoV‐Spot assay, we assessed T‐cell and antibody responses in mild, moderate and severe SARS‐CoV‐2 patients and in control samples collected before the outbreak. Results Specific T cells were assessed in 60 consecutive patients (mild, n = 26; moderate, n = 10; and severe patients, n = 24) during their follow‐up (median time from symptom onset [interquartile range]: 36 days [28;53]). T cells against M, N and S peptide pools were detected in n = 60 (100%), n = 56 (93.3%), n = 55 patients (91.7%), respectively. Using the MNS mix, IFNγ T‐CoV‐Spot assay showed a specificity of 96.7% (95% CI, 88.5–99.6%) and a specificity of 90.3% (75.2–98.0%). The frequency of reactive T cells observed with M, S and MNS mix pools correlated with severity and with levels of anti‐S1 and anti‐RBD serum antibodies. Conclusion IFNγ T‐CoV‐Spot assay is a reliable method to explore specific T cells in large cohorts of patients. This test may become a useful tool to assess the long‐lived memory T‐cell response after vaccination. Our study demonstrates that SARS‐CoV‐2 patients developing a severe disease achieve a higher adaptive immune response.

BACKGROUND:Cervical cancer screening rates are known to be strongly associated with socioeconomic status. Our objective was to assess whether the rate is also associated with an aggregated deprivation marker, defined by the location of family doctors' offices. METHODS:To access this association, we 1) collected data from the claim database of the French Health Insurance Fund about the registered family doctors and their enlisted female patients eligible for cervical screening; 2) carried out a telephone survey with all registered doctors to establish if they were carrying out Pap-smears in their practices; 3) geotracked all the doctors' offices in the smallest existing blocks of socioeconomic homogenous populations (IRIS census units) that were assigned a census derived marker of deprivation, the European Deprivation Index (EDI), and a binary variable of urbanization; and 4) we used a multivariable linear mixed model with IRIS as a random effect. RESULTS:Of 348 eligible doctors, 343 responded to the telephone survey (98.6%) and were included in the analysis, encompassing 88,152 female enlisted patients aged 25-65 years old. In the multivariable analysis (adjusted by the gender of the family doctor, the practice of Pap-smears by the doctor and the urbanization of the office location), the EDI of the doctor's office was strongly associated with the cervical cancer screening participation rate of eligible patients (p

Background and Purpose In the Aspiration vs. Stent Retriever for Successful Revascularization (ASTER) trial, which evaluated contact aspiration (CA) versus stent retriever (SR) use as first-line technique, the impact of the susceptibility vessel sign (SVS) on magnetic resonance imaging (MRI) was studied to determine its influence on trial results. Methods We included patients having undergone CA or SR for M1 or M2 occlusions, who were screened by MRI with T2* gradient recalled echo. Occlusions were classified as SVS (+) or SVS (–) in each randomization arm. Modified thrombolysis in cerebral infarction (mTICI) 2b, 2c, or 3 revascularization rates were recorded and clinical outcomes assessed by the overall distribution of modified Rankin scale (mRS) at 90 days. Results Among the 202 patients included, 143 patients were SVS (+) (70.8%; 95% confidence interval [CI], 64.5% to 77.1%). Overall, there was no difference in angiographic and clinical outcomes according to SVS status. However, compared to SR, CA achieved a lower mTICI 2c/3 rate in SVS (+) patients (risk ratio [RR] for CA vs. SR, 0.60; 95% CI, 0.51 to 0.71) but not in SVS (–) (RR, 1.11; 95% CI, 0.69 to 1.77; P for interaction=0.018). A significant heterogeneity in favor of superiority of first-line SR strategy in SVS (+) patients was also found regarding the overall mRS distribution (common odds ratio for CA vs. SR, 0.40 vs. 1.32; 95% CI, 0.21 to 0.74 in SVS (+) vs. 95% CI, 0.51 to 3.35 in SVS (–); P for interaction=0.038). Conclusions As a first line strategy, SR achieved higher recanalization rates and a more favourable clinical outcome at 3 months compared to CA when MRI shows SVS within the thrombus.

Abstract Background Evidence increases that a high or a standard dose of tranexamic acid (TA) reduces postpartum bleeding. The TRACES pharmacobiological substudy aims to establish a therapeutic strategy in hemorrhagic (H) Cesarean section (CS) with respect to the intensity of fibrinolysis by using innovative assays. Method/Design The TRACES trial is a multicenter, randomized, double-blind, placebo-controlled, TA dose-ranging study that measures simultaneously plasmatic and uterine and urine TA concentrations and the plasmin peak inhibition tested by a simultaneous thrombin plasmin generation assay described by Van Geffen (novel hemostasis assay [NHA]). Patients undergoing H CS (>800 mL) will receive blindly TA 0.5 g or 1 g or placebo. A non-hemorrhagic (NH) group will be recruited to establish plasmin generation profile. Venous blood will be sampled before, at the end, and then at 30, 60, 120, and 360 min after injection. Uterine bleeding will be sampled after injection. Urine will be sampled 2 h and 6 h after injection. The number of patients entered into the study will be 114 H + 48 NH out of the 390 patients of the TRACES clinical trial. Discussion To explore the two innovative assays, a preliminary pilot study was conducted. Blood samples were performed repeatedly in patients undergoing either a H (>800 mL) or NH (

Abstract Background Postpartum haemorrhage (PPH) is the leading cause of maternal death worldwide. Tranexamic acid (TA), an antifibrinolytic drug, reduces bleeding and transfusion need in major surgery and trauma. In ongoing PPH following vaginal delivery, a high dose of TA decreases PPH volume and duration, as well as maternal morbidity, while early fibrinolysis is inhibited. In a large international trial, a TA single dose reduced mortality due to bleeding but not the hysterectomy rate. TA therapeutic dosages vary from 2.5 to 100 mg/kg and seizures, visual disturbances and nausea are observed with the highest dosages. TA efficiency and optimal dosage in haemorrhagic caesarean section (CS) has not been yet determined. We hypothesise large variations in fibrinolytic activity during haemorrhagic caesarean section needing targeted TA doses for clinical and biological efficacy. Methods/design The current study proposal is a blinded, randomised controlled trial with the primary objective of determining superiority of either 1 g of TXA or 0.5 g of TXA, in comparison to placebo, in terms of 30% blood-loss reduction at 6 h after non-emergency haemorrhagic caesarean delivery (active PPH > 800 mL) and to correlate this clinical effect in a pharmacokinetics model with fibrinolysis inhibition measured by an innovative direct plasmin measurement regarding plasmatic TA concentration. A sample size of 342 subjects (114 per group) was calculated, based on the expected difference of 30% reduction of blood loss between the placebo group and the low-dose group, out of which 144 patients will be included blindly in the pharmaco-biological substudy. A non-haemorrhagic reference group will include 48 patients in order to give a reference for peak plasmin level. Discussion TRACES trial is expected to give the first pharmacokinetics data to determinate the optimal dose of tranexamic acid to reduce blood loss and inhibit fibrinolysis in hemorrhagic cesarean section. Trial registration ClinicalTrials.gov, ID: NCT02797119. Registered on 13 June 2016.

Abstract Background While the incidence of esophageal and gastric cancers is increasing, the prognosis of these cancers remains bleak. Endoscopy and surgery are the standard treatments for localized tumors, but multimodal treatments, associated chemotherapy, targeted therapies, immunotherapy, radiotherapy, and surgery are needed for the vast majority of patients who present with locally advanced or metastatic disease at diagnosis. Although survival has improved, most patients still present with advanced disease at diagnosis. In addition, most patients exhibit a poor or incomplete response to treatment, experience early recurrence and have an impaired quality of life. Compared with several other cancers, the therapeutic approach is not personalized, and research is much less developed. It is, therefore, urgent to hasten the development of research protocols, and consequently, develop a large, ambitious and innovative tool through which future scientific questions may be answered. This research must be patient-related so that rapid feedback to the bedside is achieved and should aim to identify clinical-, biological- and tumor-related factors that are associated with treatment resistance. Finally, this research should also seek to explain epidemiological and social facets of disease behavior. Methods The prospective FREGAT database, established by the French National Cancer Institute, is focused on adult patients with carcinomas of the esophagus and stomach and on whatever might be the tumor stage or therapeutic strategy. The database includes epidemiological, clinical, and tumor characteristics data as well as follow-up, human and social sciences quality of life data, along with a tumor and serum bank. Discussion This innovative method of research will allow for the banking of millions of data for the development of excellent basic, translational and clinical research programs for esophageal and gastric cancer. This will ultimately improve general knowledge of these diseases, therapeutic strategies and patient survival. This database was initially developed in France on a nationwide basis, but currently, the database is available for worldwide contributions with respect to the input of patient data or the request for data for scientific projects. Trial registration The FREGAT database has a dedicated website (www.fregat-database.org) and is registered on the Clinicaltrials.gov site, number NCT 02526095, since August 8, 2015.

Abstract Objective Reliable data about general practitioners performing pap-tests are insufficient. A claim code for the achievement of pap-smears exists in France, but its use by general practitioners is not known. The main purpose of this study was to highlight independent factors associated with the achievement of pap-smears by the general practitioner (GP). We carried out a descriptive and analytic epidemiologic study in 347 GPs and their 244,889 patients, registered at the Health Care Insurance Fund of Flanders. The European Deprivation Index (EDI) in the area of GP’s surgeries was specified. All GPs were questioned by telephone about their performance of pap-tests. The claim database of the insurance fund was analyzed to describe characteristics of GPs. Results The answer rate among questioned GPs was 98.8%. Pap-smears were performed in their surgeries by 182 GPs (53.1%). Among males, 45.7% performed pap-smears versus 78.4% of the female (adjusted odds-ratio = 4.5, p

Abstract Background Anemia is prevalent at pediatric intensive care unit (PICU) admission and incident during PICU stay, but little is known about anemia at PICU discharge . Anemia after critical illness is an important issue because it could impact post-PICU outcome. We aimed to estimate the prevalence of anemia at PICU discharge and to determine its risk markers. Methods This is an ancillary study of a prospective observational study on transfusion practices conducted in the PICU of a tertiary care children’s hospital. All children consecutively admitted to the PICU during a 1-year period were considered for inclusion. Data were prospectively collected from medical charts, except for hemoglobin (Hb) levels at PICU and hospital discharge that were collected retrospectively. Anemia was defined by an Hb concentration below the lower limit of the normal range for age. Results Among the 679 children retained for analysis, 390 (57.4%) were anemic at PICU discharge. After multivariate adjustment, anemia at PICU admission was the strongest risk marker of anemia at PICU discharge. The strength of this association varied according to age (interaction): The odds ratio (OR) (95% CI) of anemia at PICU discharge was 4.85 (1.67–14.11) for 1–5-month-old infants anemic versus not anemic at PICU admission, and it was 73.13 (13.43, 398.19) for adolescents anemic versus not anemic at PICU admission. Children admitted after a non-cardiac surgery had an increased risk of anemia at PICU discharge [OR 2.30 (1.37, 3.88), p = 0.002]. The proportion of anemic children differed between age categories, while the median Hb level did not exhibit significant variations according to age. Conclusions Anemia is highly prevalent at PICU discharge and is strongly predicted by anemia at PICU admission. The usual age-based definitions of anemia may not be relevant for critically ill children. The consequences of anemia at PICU discharge are unknown and deserve further scrutiny.

Abstract Background Glucose is widely used as an osmotic agent in peritoneal dialysis (PD), but exerts untoward effects on the peritoneum. The potential protective effect of a reduced exposure to hypertonic glucose has never been investigated. Methods The cohort of PD patients attending our center which tackled the challenge of a restricted use of hypertonic glucose solutions has been prospectively followed since 1992. Small-solute transport was assessed using an equivalent of the glucose peritoneal equilibration test after 6 months, and then every year. Study was stopped on July 1st, 2008, before use of biocompatible solutions. Repeated measures in patients treated with PD for 54 months were analyzed by using (1) the slopes of the linear regression for D4/D0 ratios over time computed for each individual, and (2) a linear mixed model. Results In the study period, 44 patients were treated for a total of 2376 months, 2058 without hypertonic glucose. There was one episode of peritoneal infection every 18 patient-months. The mean of slopes of the linear regression for D4/D0 ratios was found to be significantly positive (Student’s test, p

INTRODUCTION:The use of therapeutic body wraps (TBW) has been reported in small series or case reports, but has become controversial. OBJECTIVES:This is a feasibility, multicentre, randomized, controlled, open-label trial with blinded outcome assessment (PROBE design). SETTING:Children with autism and severe-injurious behaviours (SIB) were enrolled from 13 specialized clinics. INTERVENTIONS:Dry-sheet TBW (DRY group) vs. wet-sheet TBW (WET group). PRIMARY OUTCOME MEASURES:3-month change in the Aberrant Behaviour Checklist irritability score (ABC-irritability) within per-protocol (PP) sample. RESULTS:From January 2008 to January 2015, we recruited 48 children (age range: 5.9 to 9.9 years, 78.1% male). Seven patients (4 in the DRY group, 3 in the WET group) were dropped from the study early and were excluded from PP analysis. At endpoint, ABC-irritability significantly improved in both groups (means (standard deviation) = -11.15 (8.05) in the DRY group and -10.57 (9.29) in the WET group), as did the other ABC scores and the Children Autism Rating scale score. However, there was no significant difference between groups. All but 5 patients were rated as much or very much improved. A repeated-measures analysis confirmed the significant improvement in ABC-irritability scores according to time (p < .0001), with no significant difference between the two groups (group effect: p = .55; interaction time x group: p = .27). Pooling both groups together, the mean 3-month change from baseline in ABC-irritability score was -10.90 (effect size = 1.59, p < .0001). CONCLUSIONS:We found that feasibility was overall satisfactory with a slow recruitment rate and a rather good attrition rate. TBW was a safe complementary therapy in this population. There was no difference between wet and dry TBW at 3 months, and ABC-irritability significantly decreased with both wet and dry sheet TBW. To assess whether TBW may constitute an alternative to medication or behavioural intervention for treating SIB in ASD patients, a larger randomized comparative trial (e.g. TBW vs. antipsychotics) is warranted. TRIAL REGISTRATION:ClinicalTrials.gov NCT03164746.

Dietary n-3 long-chain PUFAs (LC-PUFAs) are associated with improvement in the parameters of the metabolic syndrome (MetS). Glucokinase regulatory protein (GCKR) is a key protein regulating intracellular glucose disposal. Our aim was to investigate: i) the relationship between the GCKR rs1260326 (Pro446Leu) polymorphism and parameters of the MetS; and ii) a potential influence of n-3 and n-6 LC-PUFA levels on this relationship in the HELENA study (1,155 European adolescents). Linear regression analyses were performed to study the association between rs1260326 and the outcomes of interest. Interactions between rs1260326 and LC-PUFA levels on outcomes were explored. The T allele of rs1260326 was associated with higher serum TG concentrations compared with the C allele. In contrast to n-6 LC-PUFA levels, a significant interaction (P = 0.01) between rs1260326 and total n-3 LC-PUFA levels on serum TG concentrations was observed. After stratification on the n-3 LC-PUFA median values, the association between rs1260326 and TG concentration was significant only in the group with high n-3 LC-PUFA levels. In conclusion, this is the first evidence that n-3 LC-PUFAs may modulate the impact of the GCKR rs1260326 polymorphism on TG concentrations in adolescents. Several molecular mechanisms, in link with glucose uptake, could explain these findings.

BackgroundHigh blood pressure (BP) is associated with worse clinical outcomes in the setting of acute ischemic stroke, but the optimal blood pressure target is still a matter of debate. We aimed to study the association between baseline BP and mortality in acute ischemic stroke patients treated by mechanical thrombectomy. Methods and ResultsA total of 1332 acute ischemic stroke patients treated by mechanical thrombectomy were enrolled (from January 2012 to June 2016) in the ETIS (Endovascular Treatment in Ischemic Stroke) registry. Linear and polynomial logistic regression models were used to assess the association between BP and mortality and functional outcome at 90 days. Highest mortality was found at lower and higher baseline systolic blood pressure (SBP) values following a J‐ or U‐shaped relationship, with a nadir at 157 mm Hg (95% confidence interval 143‐170). When SBP values were categorized in 10–mm Hg increments, the odds ratio for all‐cause mortality was 3.78 (95% confidence interval 1.50‐9.55) for SBP

Systemic sclerosis-related interstitial lung disease (SSc-ILD) is the leading cause of death in SSc. In this study, we aimed to describe the baseline severity and evolution of forced vital capacity (FVC) and diffusing capacity for carbon monoxide (DLCO) in patients with SSc-ILD and to assess the baseline clinical, biological and high-resolution CT scan (HRCT) predictors of this evolution. Baseline and serial FVC and DLCO were collected in 75 SSc-ILD patients followed during 6.4±4.2 years (n = 557 individual data). FVC and DLCO evolution was modelled using a linear mixed model with random effect. During follow-up, FVC was stable while DLCO significantly decreased (-1.5±0.3%/year (p

Postnatal corticosteroids (PNC) were widely used to treat and prevent bronchopulmonary dysplasia in preterm infants until studies showed increased risk of cerebral palsy and neurodevelopmental impairment. We aimed to describe PNC use in Europe and evaluate the determinants of their use, including neonatal characteristics and adherence to evidence-based practices in neonatal intensive care units (NICUs).3917/4096 (95,6%) infants born between 24 and 29 weeks gestational age in 19 regions of 11 European countries of the EPICE cohort we included. We examined neonatal characteristics associated with PNC use. The cohort was divided by tertiles of probability of PNC use determined by logistic regression analysis. We also evaluated the impact of the neonatal unit's reported adherence to European recommendations for respiratory management and a stated policy of reduced PNC use.PNC were prescribed for 545/3917 (13.9%) infants (regional range 3.1-49.4%) and for 29.7% of infants in the highest risk tertile (regional range 5.4-72.4%). After adjustment, independent predictors of PNC use were a low gestational age, small for gestational age, male sex, mechanical ventilation, use of non-steroidal anti-inflammatory drugs to treat persistent ductus arteriosus and region. A stated NICU policy reduced PNC use (odds ratio 0.29 [95% CI 0.17; 0.50]).PNC are frequently used in Europe, but with wide regional variation that was unexplained by neonatal characteristics. Even for infants at highest risk for PNC use, some regions only rarely prescribed PNC. A stated policy of reduced PNC use was associated with observed practice and is recommended.

[This corrects the article DOI: 10.1371/journal.pone.0170234.].

Objective: The question of whether breastfeeding has a protective effect against the development of overweight or obesity later in life remains controversial, especially during adolescence. The objective was to assess the relationship between breastfeeding and adolescents' body composition. Methods: The HELENA study is a cross-sectional study involving 3,528 adolescents from 10 European cities. The outcome measures were body weight and height, subscapular skinfolds as well as waist circumferences. Breastfeeding, smoking status, and parental socioeconomic status were assessed by self-administered questionnaires. Dietary intake was recorded using two 24-hour recall surveys. Two adjustment approaches were used: i) covariance analysis adjusted for confounding factors (propensity score adjustment) and ii) multivariate quantile regression. Results: After adjustment, no significant associations were observed between breastfeeding and body composition parameters (BMI Z-score; sum of skinfolds; waist-to-height ratio). An adjusted quantile regression analysis showed a non-significant trend for a protective effect of breastfeeding toward the highest percentiles of adiposity in boys but not in girls. This is of particular interest with respect to the superiority of the waist-to-height ratio over waist circumference and BMI for detecting cardiometabolic risk factors. Conclusion: This first European study, including a large set of factors influencing adolescents' body composition, showed a non-significant trend toward a protective effect of breastfeeding on highest percentiles of adolescent's abdominal adiposity.

BACKGROUND:Axial disorders are considered to appear late in the course of Parkinson's disease (PD). The associated impact on quality of life (QoL) and survival and the lack of an effective treatment mean that understanding and treating axial disorders is a key challenge. However, upper-body axial disorders (namely dysarthria, swallowing and breathing disorders) have never been prospectively assessed in early-stage PD patients. OBJECTIVES:To characterize upper-body axial symptoms and QoL in consecutive patients with early-stage PD. METHODS:We prospectively enrolled 66 consecutive patients with early-stage PD (less than 3 years of disease progression) and assessed dysarthria, dysphagia and respiratory function (relative to 36 controls) using both objective and patient-reported outcomes. RESULTS:The mean disease duration was 1.26 years and the mean UPDRS motor score was 19.4 out of 108. 74% of the patients presented slight dysarthria (primarily dysprosodia). Men appeared to be more severely affected (i.e. dysphonia). This dysfunction was strongly correlated with low swallowing speed (despite the absence of complaints about dysphagia), respiratory insufficiency and poor QoL. Videofluorography showed that oral-phase swallowing disorders affected 60% of the 31 tested patients and that pharyngeal-phase disorders affected 21%. 24% of the patients reported occasional dyspnea, which was correlated with anxiety in women but not in men. Marked diaphragmatic dysfunction was suspected in 42% of the patients (predominantly in men). CONCLUSION:Upper body axial symptoms were frequent in men with early-stage PD, whereas women presented worst non-motor impairments. New assessment methods are required because currently available tools do not reliably detect these upper-body axial disorders.

Purpose. To evaluate the effects of repeated intravitreal dexamethasone implant (DI) (Ozurdex®) in eyes with macular edema (ME) due to retinal vein occlusion (RVO). Methods. Multicenter observational study including patients who received more than three consecutive DI on an “as-needed” basis for the treatment of ME in RVO. Results. A total of 18 eyes were included for analysis. Mean interval of retreatment with DI was 5.1 months between the first and second DI and 5.4 months following the second DI. Baseline BCVA was 0.74 ± 0.08 log-Mar; it significantly improved to 0.45 ± 0.04 2 months after the 3rd DI. There was no significant difference between the 3 first postinjection BCVA. CMT decreased from 617 μm ± 120 μm (baseline) to 330 ± 109 μm two months after the third DI. Elevated intraocular pressure occurred in 50% and was controlled medically. Cataract progression leading to cataract surgery occurred in 69% of phakic eyes after a mean interval of 17 months. Conclusion. Repeated DI on an “as-needed” basis, with a retreatment interval

PurposeAcute respiratory failure (ARF) is a common life-threatening complication in morbidly obese patients with obesity hypoventilation syndrome (OHS). We aimed to identify the determinants of noninvasive ventilation (NIV) success or failure for this indication.MethodsWe prospectively included 76 consecutive patients with BMI>40 kg/m2 diagnosed with OHS and treated by NIV for ARF in a 15-bed ICU of a tertiary hospital.ResultsNIV failed to reverse ARF in only 13 patients. Factors associated with NIV failure included pneumonia (n = 12/13, 92% vs n = 9/63, 14%; pConclusionsMultiple organ failure and pneumonia were the main factors associated with NIV failure and death in morbidly obese patients in hypoxemic ARF. On the opposite, NIV was constantly successful and could be safely pushed further in case of severe hypercapnic acute respiratory decompensation of OHS.

Amylase concentration in respiratory secretions was reported to be a potentially useful marker for aspiration and pneumonia. The aim of this study was to determine accuracy of α-amylase in diagnosing microaspiration in critically ill patients.Retrospective analysis of prospectively collected data collected in a medical ICU. All patients requiring mechanical ventilation for at least 48 h, and included in a previous randomized controlled trial were eligible for this study, provided that at least one tracheal aspirate was available for α-amylase measurement. As part of the initial trial, pepsin was quantitatively measured in all tracheal aspirates during a 48-h period. All tracheal aspirates were frozen, allowing subsequent measurement of α-amylase for the purpose of the current study. Microaspiration was defined as the presence of at least one positive tracheal aspirate for pepsin (>200 ng.mL-1). Abundant microaspiration was defined as the presence of pepsin at significant level in >74% of tracheal aspirates.Amylase was measured in 1055 tracheal aspirates, collected from 109 patients. Using mean α-amylase level per patient, accuracy of α-amylase in diagnosing microaspiration was moderate (area under the receiver operator curve 0.72±0.05 [95%CI 0.61-0.83], for an α-amylase value of 1685 UI.L-1). However, when α-amylase levels, coming from all samples, were taken into account, area under the receiver operator curve was 0.56±0.05 [0.53-0.60]. Mean α-amylase level, and percentage of tracheal aspirates positive for α-amylase were significantly higher in patients with microaspiration, and in patients with abundant microaspiration compared with those with no microaspiration; and similar in patients with microaspiration compared with those with abundant microaspiration. α-amylase and pepsin were significantly correlated (r2 = 0.305, p = 0.001).Accuracy of mean α-amylase in diagnosing microaspiration is moderate. Further, when all α-amylase levels were taken into account, α-amylase was inaccurate in diagnosing microaspiration, compared with pepsin.

Based on the pathophysiological role of adenosine A2A receptors in HD, we have evaluated the association of the 1976C/T single-nucleotide polymorphism in the ADORA2A gene (rs5751876) with residual age at onset (AAO) in HD. The study population consisted of 791 unrelated patients belonging to the Huntington French Speaking Network. The variability in AAO attributable to the CAG repeats number was calculated by linear regression using the log (AAO) as the dependent variable, and the respective rs5751876 genotypes as independent variables. We show that the rs5751876 variant significantly influences the variability in AAO. The R2 statistic rose slightly but significantly (p=0.019) when rs5751876 T/T genotype was added to the regression model. Patients harbouring T/T genotype have an earlier AAO of 3.8 years as compared to C/C genotype (p=0.02). Our data thus strengthens the pathophysiological role of A2A receptors in Huntington's disease.

Dehydration secondary to gastroenteritis is one of the most common reasons for office visits and hospital admissions. The indicator most commonly used to estimate dehydration status is acute weight loss. Post-illness weight gain is considered as the gold-standard to determine the true level of dehydration and is widely used to estimate weight loss in research. To determine the value of post-illness weight gain as a gold standard for acute dehydration, we conducted a prospective cohort study in which 293 children, aged 1 month to 2 years, with acute diarrhea were followed for 7 days during a 3-year period. The main outcome measures were an accurate pre-illness weight (if available within 8 days before the diarrhea), post-illness weight, and theoretical weight (predicted from the child's individual growth chart). Post-illness weight was measured for 231 (79%) and both theoretical and post-illness weights were obtained for 111 (39%). Only 62 (21%) had an accurate pre-illness weight. The correlation between post-illness and theoretical weight was excellent (0.978), but bootstrapped linear regression analysis showed that post-illness weight underestimated theoretical weight by 0.48 kg (95% CI: 0.06-0.79, p