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School refusal (SR) is a form of school attendance problem (SAP) that requires specific mental health care. Despite improvements in the definition of SAPs, the course of SR is not well characterized. To explore three-year patterns of SR course in children, as reported by their parents, we deployed an anonymous web-based survey. We defined SR onset as the absence of ≥ 2 school weeks during one academic year, combined with emotional distress. We defined standard SR trajectories using sequence analysis of parents' recollection of three consecutive years of school attendance. We obtained 1970 responses, 1328 (67%) completed by a parent and meeting the definition of SR. Of these, 729 (55%) responses included three years of school attendance recollection. We identified five prototypical trajectories of SR: two profiles for children: beaded absences (n = 272), and rapid recovery (n = 132); and three for adolescents: prolonged recovery (n = 93), gradual decline (n = 89), and rapid decline (n = 143). We found five distinct trajectories of retrospective recall of SR course. Through pattern recognition, this typology could help with timely identification of SR and implementation of evidence-based interventions to optimize outcomes. Prospective replication of these findings and their field application is warranted. [ABSTRACT FROM AUTHOR]

Symptomatic effects of mental disorders in parents could bias their reporting on their child's mental health. This study aimed to investigate the measurement invariance of the French version of the parental Strengths and Difficulties Questionnaire (SDQ) across parental mental health in a sample (N = 20,765) of parents of children aged 3 to 17 years in France. Confirmatory factor analysis (CFA) and Exploratory Structural Equation Modelling (ESEM) were used to evaluate the fit of three known alternative SDQ factor structures (five, three, or second-order factor structures). Invariance was tested across parental mental health (present anxiety and depressive symptoms, psychiatric history) and across socio-demographic characteristics (child's age, child's gender, parent's gender, parent's educational level). CFA models showed a poor fit, while all ESEM models achieved acceptable or good fit, with the five-factor model presenting the best fit. Invariance was observed for all characteristics tested, indicating that the SDQ can be used to study the links between parental mental health and their child's mental health without bias. However, ESEM showed that the hyperactivity/inattention and conduct problems dimensions were not well differentiated in the French version of the SDQ. [ABSTRACT FROM AUTHOR]

Cold atmospheric pressure plasma (ionized gas) is an innovative medical tool for the treatment of infected wounds thanks to its potential to inactivate drug-resistant microorganisms and promote tissue regeneration and vascularization. The low power consumption, compactness, and versatility of Cold Atmospheric Pressure Plasma (CAPP) devices make them an ideal tool for risk mitigation associated with human spaceflights. This work presents results in microgravity on the operability of CAPP and its antimicrobial effect. The experiments carried out in parabolic flights make it possible to optimize the treatment conditions (i.e., the distance, the gas mixture) and to obtain the rapid inactivation (<15 s) of Escherichia coli samples. Interestingly, the inactivation efficiency of CAPP was higher during parabolic flights than under terrestrial conditions. Overall, these results encourage the further development of CAPP medical devices for its implementation during human spaceflights. [ABSTRACT FROM AUTHOR]

Background: Reducing nivolumab dose intensity could increase patients' life quality and decrease the financial burden while maintaining efficacy. The aims of this study were to develop a population PK model of nivolumab based on data from unselected metastatic cancer patients and to simulate extended-interval regimens allowing to maintain minimal effective plasma concentrations (MEPC). Methods: Concentration-time data (992 plasma nivolumab concentrations, 364 patients) were modeled using a two-compartment model with linear elimination clearance in Monolix software. Extended-interval regimens allowing to maintain steady-state trough concentrations (Cmin,ss) above the MEPC of 2.5 mg/L or 1.5 mg/L in >90% of patients were simulated. Results: Increasing 3-times the dosing interval from 240 mg every two weeks (Q2W) to Q6W and 2-times from 480 mg Q4W to Q8W resulted in Cmin,ss above 2.5 mg/L in 95.8% and 95.4% of patients, respectively. 240 mg Q8W and 480 mg Q10W resulted in Cmin,ss above 1.5 mg/L in 91.0% and 91.8% of patients, respectively. Selection of a 240 mg Q6W regimen would decrease by 3-fold the annual treatment costs compared to standard regimen of 240 mg Q2W (from 78,744€ to 26,248€ in France). Conclusions: Clinical trials are warranted to confirm the non-inferiority of extended-interval compared to standard regimen. [ABSTRACT FROM AUTHOR]

Children's screen time increased as a result of the COVID-19 pandemic. In the summer of 2021, we explored the association between high screen time over a period of one year since May 2020 and behavioural problems among children and adolescents. The data were derived from the French EpiCov cohort study, collected in spring 2020, autumn 2020, and spring 2021. Participants (N = 1089) responded to online or telephone interviews about one of their children aged 3 to 14 years. Screen time was categorized as high if the daily mean screen time exceeded recommendations at each collection time. The Strengths and Difficulties Questionnaire (SDQ) was completed by parents to identify internalizing (emotional or peer problems) and externalizing (conduct problems or hyperactivity/inattention) behaviours in their children. Among the 1,089 children, 561 (51.5%) were girls, the average age was 8.6 years (SD 3.7). Internalizing behaviours: High screen time was not associated with internalizing behaviours (OR [95% CI] 1.20 [0.90–1.59]) or emotional symptoms (1.00 [0.71–1.41]) while it was associated with peer problems (1.42 [1.04–1.95]). Externalizing behaviours: High screen time was associated with externalizing problems (1.63 [1.01–2.63]) and conduct problems (1.91 [1.15–3.22]) only among older children aged 11 to 14 years. No association with hyperactivity/inattention was found. In a French cohort, exploration of persistent high screen time in the first year of the pandemic and behaviour difficulties in Summer 2021 resulted in mixed findings according to behaviour's type and children's age. These mixed findings warrant further investigation into screen type and leisure/school screen use to enhance future pandemic responses appropriate for children. [ABSTRACT FROM AUTHOR]

Purpose: Pazopanib is approved in advanced renal cell carcinoma (RCC) and soft-tissue sarcoma at a flat-fixed dose despite a large pharmacokinetics interindividual variability and a narrow therapeutic index. To our knowledge, pazopanib exposure in patients with gastrointestinal resections (GIR) has not been described. This report focuses on feasibility of pharmacokinetics-guided dose escalation in these patients and clinical implications for their management. Method: A retrospective data collection was performed for three patients with GIR treated with pazopanib, including pazopanib plasma concentrations (high-performance liquid chromatography with UV detection) and treatment adherence (Girerd score). Case presentation: First patient (55-year-old man, RCC, gastric bypass surgery) pazopanib Cmin,ss at day 39 was 4.1 mg/L. Dose escalation to 1800 mg/day fractionated allowed to reach Cmin,ss of 18.5 mg/L (target threshold in RCC patients: 20.5 mg/L). Patient 2 (50-year-old woman, metastatic myxofibrosarcoma, gastric band) showed Cmin,ss of 4.0 mg/L at day 13. In patient 3 (49-year-old man, gastric malignant peripheral nerve sheath tumor, gastrectomy), Cmin,ss at day 13 was 2.7 mg/L. For these two patients, intake with food and dose fractioning only slightly increased pazopanib Cmin,ss to 12.0 mg/L and 6.5 mg/L, respectively (therapeutic threshold in sarcoma patients: 27 mg/L). Treatment adherence was good in all patients. Conclusion: Optimal pazopanib exposure cannot be achieved in patients with GIR, and thus, other therapeutic strategies should be encouraged. Pretherapeutic assessment seems crucial to evaluate factors as bariatric surgery that may impact pazopanib concentrations. Therapeutic drug monitoring could be helpful to optimize pazopanib response in these patients. [ABSTRACT FROM AUTHOR]

Background: The REGOBONE multi-cohort study explored the efficacy and safety of regorafenib for patients with advanced bone sarcomas; this report details the Ewing sarcoma (ES) cohort. Methods: Patients with relapsed ES progressing despite prior standard therapy, were randomised (2:1) to receive regorafenib or placebo. Patients on placebo could crossover to receive regorafenib after centrally confirmed progression. The primary endpoint was the progression-free rate at 8 weeks. With one-sided α of 0.05, and 80% power, at least 14/24 progression-free patients at 8 weeks were needed for success. Results: From September 2014 to November 2019, 41 patients were accrued. 36 patients were evaluable for efficacy: 23 on regorafenib and 13 on placebo. Thirteen patients (56%; one-sided 95% CI [37.5%–[)) were progression-free at 8 weeks on regorafenib vs. 1 (7.7%; 95% CI [0.4%–[) on placebo. Median PFS was 11.4 weeks on regorafenib, and 3.9 weeks on placebo. Ten placebo patients crossed over to receive regorafenib after progression. The most common grade ≥3 regorafenib-related adverse events were pain (22%), asthenia (17%), thrombocytopenia (13%) and diarrhoea (13%). Conclusion: Although the primary endpoint was not met statistically in this randomised cohort, there is evidence to suggest that regorafenib might modestly delay tumour progression in relapsed ES after failure of prior chemotherapy. [ABSTRACT FROM AUTHOR]

Abstract Although lung cancer patients harboring EGFR mutations benefit from treatment with EGFR‐tyrosine kinase inhibitors (EGFR‐TKI), most of them rapidly relapse. RHOB GTPase is a critical player in both lung carcinogenesis and the EGFR signaling pathway; therefore, we hypothesized that it could play a role in the response to EGFR‐TKI. In a series of samples from EGFR‐mutated patients, we found that low RHOB expression correlated with a good response to EGFR‐TKI treatment while a poor response correlated with high RHOB expression (15.3 versus 5.6 months of progression‐free survival). Moreover, a better response to EGFR‐TKI was associated with low RHOB levels in a panel of lung tumor cell lines and in a lung‐specific tetracycline‐inducible EGFRL858R transgenic mouse model. High RHOB expression was also found to prevent erlotinib‐induced AKT inhibition in vitro and in vivo. Furthermore, a combination of the new‐generation AKT inhibitor G594 with erlotinib induced tumor cell death in vitro and tumor regression in vivo in RHOB‐positive cells. Our results support a role for RHOB/AKT signaling in the resistance to EGFR‐TKI and propose RHOB as a potential predictor of patient response to EGFR‐TKI treatment.

Emerging research suggests that the prevalence of child and adolescent mental health problems has increased considerably during the COVID-19 crisis. However, there have been few longitudinal studies on children's mental health issues according to their social determinants in this context, especially in Europe. Our aim was to investigate the association between family socioeconomic status (SES) and children' mental health during the period of school closure due to COVID-19. Longitudinal data came from 4575 children aged 8–9 years old in 2020 and participating in the ELFE population-based birth cohort that focuses on children's health, development and socialization. Parents completed the Strengths and Difficulties Questionnaire (SDQ) when children were (a) 5 years of age and (b) 9 years of age, which corresponded to the period of school closure due to the COVID-19 pandemic in France. We retrieved data from the ELFE cohort collected on children from birth to age 5 years (birth, 1 year, 2 years, 3,5 years and 5 years). Socioeconomic status (SES) was measured based on information obtained when the child was 5 years old. Data were analyzed using multinomial logistic regression models. Children's elevated levels of symptoms of Attention-deficit/Hyperactivity disorder (ADHD) during the period of school closure were significantly associated with prior low family SES (aOR 1.26, 95% CI 1.08–1.48). Children's elevated symptoms of hyperactivity/inattention and of emotional symptoms were associated with decline in income during the COVID crisis (respectively, aOR 1.38, 95% CI 1.16–1.63 and aOR 1.23, 95% CI 1.01–1.51). Moreover, when testing interactions, a low prior SES was significantly associated with a higher risk of emotional symptoms aOR 1.54 (1.07–2.21), only for children whose families experienced a decline in income, while gender, parental separation and prior mental health difficulties were not associated. This study underlines the impact of the financial crisis related to the COVID-19 epidemic on children's mental health. Both pre-existing family SES before lockdown and more proximal financial difficulties during the COVID crisis were negatively associated with children's psychological difficulties during the period of school closure. The pandemic appears to exacerbate mental health problems in deprived children whose families suffer from financial difficulties. [ABSTRACT FROM AUTHOR]

Some studies have demonstrated that Action Observation (AO) could help patients with aphasia to recover use of verbs. However, the role of kinematics in this effect has remained unknown. The main aim was to assess the effectiveness of a complementary intervention based on the observation of action kinematics in patients with aphasia. Seven aphasic patients (3 males, 4 females) aged between 55 and 88 years participated in the studies. All patients received a classical intervention and an additional, specific intervention based on action observation. This consisted in visualizing a static image or a point-light sequence representing a human action and in trying to name the verb representing the action. In each session, 57 actions were visualized: 19 represented by a static drawing, 19 by a non-focalized point-light sequence, i.e., a point-light display with all dots in white, and 19 by a focalized point-light sequence, i.e., a point-light display (PLD) with the dots corresponding to the main limbs in yellow. Before (pre-test) and after (post-test) the intervention, each patient performed the same denomination task, in which all actions were presented in photographs. The results showed a significant improvement in performance between pre and post-test, but only when the actions were presented in focalized and non-focalized point-light sequences during the intervention. The presentation of action kinematics seems crucial in the recovery of verbs in patients with aphasia. This should be considered by speech therapists in their interventions. [ABSTRACT FROM AUTHOR]

Purpose: Pemetrexed has shown efficacy as monotherapy or in combination with platinum salts in the treatment of non-small cell lung cancer and mesothelioma. However, severe hematological toxicities induced by pemetrexed-based chemotherapy have been observed. Some studies have suggested that drug interactions may be associated with pemetrexed toxicity. The objective of this study was to determine predictive factors, including drug interactions, associated with pemetrexed toxicity. Methods: This retrospective open monocentric study included patients consecutively treated with pemetrexed after a multidisciplinary risk assessment. Patients who experienced toxicity of grade 3 or 4 according to the Common Terminology Criteria for Adverse Events v5.0, or a grade 2 leading to a change in management, during the first four courses of pemetrexed, were assigned to the early limiting toxicities (ELT) group. Univariate and multivariable logistic regression models were used to test the association variables with the occurrence of ELT. Results: Seventy-four patients were included in this study (median age: 67 years, with non-small cell lung cancer adenocarcinoma (88%), mesothelioma (7%), or others (5%). Thirty-six patients (49%) were assigned to the ELT group (27 grades 3 and 4; 9 grade 2 with management modification). Three baseline factors were associated with pemetrexed ELT in univariate and multivariate analysis: cystatin clearance (p = 0.0135), albumin level (p = 0.0333), and proton pump inhibitors use (p = 0.035). Conclusion: To conclude, ELT induced by pemetrexed-based treatments occur frequently in cancer patients in a real-world setting. A pretherapeutic assessment before pemetrexed initiation should include three major checkpoints: use of proton pump inhibitors, sarcopenia, and denutrition evaluation. [ABSTRACT FROM AUTHOR]

Several risk factors of children's mental health issues have been identified during the pandemic of COronaVIrus Disease first appeared in 2019 (COVID-19). This study aims to fill the knowledge gap regarding the association between parents' and children's mental health issues during the COVID-19 school closure in France. We conducted a cross-sectional analysis of data collected in the SAPRIS-ELFE study during the COVID-19 pandemic in France. Using multinomial logistic regressions, we estimated associations between parents' and children's mental health issues. Symptoms of anxiety were assessed by the General Anxiety Disorder-7 (GAD-7) and depression by the Patient Health Questionnaire-9 (PHQ-9) for the parents. Hyperactivity/inattention and emotional symptoms in children were assessed by the Strengths and Difficulties Questionnaire (SDQ). The sample included 3496 children aged 8 to 9 years, of whom 50.0% were girls. During the school closure, 7.1% of responding parents had moderate to severe levels of anxiety and 6.7% had moderate to severe levels of depression. A total of 11.8% of the children had an abnormal hyperactivity/inattention score and 6.6% had an abnormal emotional symptoms score. In multivariate regression models, parental moderate to severe level of anxiety and moderate to severe level of depression were associated with abnormal hyperactivity-inattention score (adjusted Odds Ratio (aOR) 3.31; 95% Confidence Interval (CI) 2.33–4.70 and aOR 4.65; 95% CI 3.27–6.59, respectively) and abnormal emotional symptoms score in children (aOR 3.58; 95% CI 2.33–5.49 and aOR 3.78; 95 CI 2.47–5.78 respectively). Children whose parents have symptoms of anxiety and/or depression have an increased likelihood of symptoms of hyperactivity/inattention and emotional symptoms during school closures in France due to COVID-19. Our findings suggest that public health initiatives should target parents and children to limit the impact of such crises on their mental health issues. [ABSTRACT FROM AUTHOR]

Economic uncertainty and family dynamics are strictly connected. The increasing uncertainty generated by the Covid-19 pandemic is thus likely to affect couple relationships and stability, with potential opposite effects. Using data from the nationally representative EPICOV survey, that followed individuals throughout the first year of pandemic in France, we examined separation rates and how these were associated with different measures of employment and income uncertainty, including both pre-pandemic conditions and changes occurred during and after the first lockdown in Spring 2020 in France. Our results show increased rates of separation, especially among younger people, during the 6 months after the first lockdown, and a return to rates more similar to those observed in usual times, afterwards. Individuals who were unemployed and had lower income before the beginning of the pandemic were more likely to separate soon after the lockdown, while changes in employment conditions due to the lockdown were not linked with a higher separation risk. The job protection and the income compensation provided by the French state, as well a less stigmatising effect of unemployment occurred during the covid crisis, may explain the absence of effect. Self-declared deterioration in financial condition, especially when declared by men, was associated with higher separation risk for the whole year of observation. [ABSTRACT FROM AUTHOR]

The purpose of this study is to clarify the relationship between having a chronic condition (CC) and several types of risky sexual behaviour (RSB) among adolescents and young adults. We used data from a multicentre cross-sectional study carried out on 14,431 adolescents from 137 French schools. Logistic regression was used to assess the association between several types of RSB and CCs among the 2680 participants aged 17 years or over who reported sexual intercourse. Survival analysis was conducted to assess the association between CCs and age at first sexual intercourse across the whole sample. Analyses were conducted separately by gender with and without adjustment for the parents' education level, early menarche and subjective wellbeing (relationship with mother and father, depression, perceived health status and liking school). Among boys, having a CC was associated with a higher risk of RSB in both univariate (OR: 1.58 [95% CI: 1.10–2.27]) and multivariate analyses (aOR: 1.62 [95% CI: 1.11–2.38]). Among girls, the association between chronic condition and RSB in univariate analysis was non-significant (OR: 1.30 [95% CI: 0.97–1.76]) and disappeared after adjustment on subjective wellbeing (aOR: 1.08 [95% CI: 0.78–1.49]). There was no association between CC and age at first sexual intercourse. Conclusion: There were major gender differences. Boys with a CC were more prone to engage in RSB independent of their subjective wellbeing, whereas in girls, subjective wellbeing seemed to mediate the relationship between CC and RSB. Clinicians should be aware of those gender differences in order to deliver preventive strategies regarding sexuality that target both genders. What is Known: • Young people with chronic conditions have a higher likelihood of engaging in risky sexual behaviour. • Engaging in such behaviours can be much more costly, as it can weaken their underlying state of health. What is New: • We found major gender differences. Boys were more prone to engage in risky behaviour independent of their subjective wellbeing, whereas in girls, it seemed to play an important role. • By understanding how risky sexual behaviour differs according to gender, clinicians can deliver prevention messages that target both genders. [ABSTRACT FROM AUTHOR]

Inclusion of students with Autism Spectrum Disorder (ASD) in mainstream schools has a positive impact on their social and daily living behaviors. Our objective was to identify clinical and socio-demographic variables promoting or limiting inclusion in mainstream school through childhood and adolescence. The EpiTED study is a long-term, prospective, multicenter cohort of 281 ASD children included before the age of 7, with a 10-year follow-up in France. Variables significantly linked to inclusion in mainstream school were identified using a mixed-effect logistic regression model: greater autonomy [OR = 1.45 (1.29–1.63)], lesser symptom severity [OR = 0.96 (0.92–0.99)] and fewer siblings [OR = 0.86 (0.75–0.99)]. In the multivariate model, the probability for a child of being included in mainstream school decreased over time [OR = 0.91 (0.85–0.97)], i.e. with age. [ABSTRACT FROM AUTHOR]

Future long-duration human spaceflight will require developments to limit biocontamination of surface habitats. The MATISS (Microbial Aerosol Tethering on Innovative Surfaces in the international Space Station) experiments allowed for exposing surface treatments in the ISS (International Space Station) using a sample-holder developed to this end. Three campaigns of FDTS (perFluoroDecylTrichloroSilane) surface exposures were performed over monthly durations during distinct periods. Tile scanning optical microscopy (×3 and ×30 magnifications) showed a relatively clean environment with a few particles on the surface (0.8 to 7 particles per mm2). The varied densities and shapes in the coarse area fraction (50–1500 µm2) indicated different sources of contamination in the long term, while the bacteriomorph shapes of the fine area fraction (0.5–15 µm2) were consistent with microbial contamination. The surface contamination rates correlate to astronauts' occupancy rates on board. Asymmetric particles density profiles formed throughout time along the air-flow. The higher density values were located near the flow entry for the coarse particles, while the opposite was the case for the fine particles, probably indicating the hydrophobic interaction of particles with the FDTS surface. [ABSTRACT FROM AUTHOR]

Key message: We investigate the genetic basis of panicle architecture in switchgrass in two mapping populations across a latitudinal gradient, and find many stable, repeatable genetic effects and limited genetic interactions with the environment. Grass species exhibit large diversity in panicle architecture influenced by genes, the environment, and their interaction. The genetic study of panicle architecture in perennial grasses is limited. In this study, we evaluate the genetic basis of panicle architecture including panicle length, primary branching number, and secondary branching number in an outcrossed switchgrass QTL population grown across ten field sites in the central USA through multi-environment mixed QTL analysis. We also evaluate genetic effects in a diversity panel of switchgrass grown at three of the ten field sites using genome-wide association (GWAS) and multivariate adaptive shrinkage. Furthermore, we search for candidate genes underlying panicle traits in both of these independent mapping populations. Overall, 18 QTL were detected in the QTL mapping population for the three panicle traits, and 146 unlinked genomic regions in the diversity panel affected one or more panicle trait. Twelve of the QTL exhibited consistent effects (i.e., no QTL by environment interactions or no QTL × E), and most (four of six) of the effects with QTL × E exhibited site-specific effects. Most (59.3%) significant partially linked diversity panel SNPs had significant effects in all panicle traits and all field sites and showed pervasive pleiotropy and limited environment interactions. Panicle QTL co-localized with significant SNPs found using GWAS, providing additional power to distinguish between true and false associations in the diversity panel. [ABSTRACT FROM AUTHOR]

Objective: The COVID-19 epidemic has spread worldwide since December 2019. To contain it, preventive measures including social distancing, economic shutdown, and school closures were introduced, carrying the risk of mental health burden in adults and children. Although the knowledge base regarding children's response to trauma and adverse events in general has broadened, descriptions of their mental health during epidemics remain scarce. In particular, the role of family socioeconomic characteristics and parental mental health are poorly understood. Methods: We assessed the correlates of children's emotional difficulties and symptoms of hyperactivity/inattention during the COVID-19 lockdown in a French community-based sample. Data came from 432 community-based parents (27–46 years, TEMPO cohort) and their children (mean age 6.8 ± 4.1) interviewed online. Children's symptoms of emotional difficulties and hyperactivity/inattention were assessed using the parent-reported Strengths and Difficulties Questionnaire during the 5th week of home confinement. Family socioeconomic characteristics and parental mental health and substance use were assessed weekly during the first 5 weeks of home confinement. Data were analyzed using logistic regression models. Results: 7.1% of children presented symptoms of emotional difficulties and 24.7% symptoms of hyperactivity/inattention. Family financial difficulties and parental symptoms of anxiety and depression, as well as children's sleeping difficulties and screen time, were associated with the presence of psychological difficulties. Conclusion: Children's emotional and behavioural difficulties are associated with parental mental health and socioeconomic difficulties. In the unprecedented situation of the COVID-19 epidemic, parents and professionals involved in caring for children should pay special attention to their mental health needs. [ABSTRACT FROM AUTHOR]

Background: The interplay between age and symptoms intensity on antibody response to SARS-CoV-2 infection has not been studied in a general population setting. Methods: We explored the serologic profile of anti-SARS-CoV-2 antibodies after the first wave of the pandemic, by assessing IgG against the spike protein (ELISA-S), IgG against the nucleocapsid protein (ELISA-NP) and neutralizing antibodies (SN) in 82,126 adults from a French population-based multi-cohort study. Results: ELISA-S positivity was increased in 30- to 49-year-old adults (8.5%) compared to other age groups (5.6% in 20- to 29-year-olds, 2.8% in ≥ 50-year-olds). In the 3681 ELISA-S positive participants, ELISA-NP and SN positivity exhibited a U-shaped relationship with age, with a lower rate in 30- to 49-year-old adults, and was strongly associated with COVID-19-like symptoms. Conclusion: Our study confirms the independent role of age and symptoms on the serologic profile of anti-SARS-CoV-2 antibodies, but the non-linear relationship with age deserves further investigation. [ABSTRACT FROM AUTHOR]

COVID-19 limitation strategies have led to widespread school closures around the world. The present study reports children's mental health and associated factors during the COVID-19 school closure in France in the spring of 2020. We conducted a cross-sectional analysis using data from the SAPRIS project set up during the COVID-19 pandemic in France. Using multinomial logistic regression models, we estimated associations between children's mental health, children's health behaviors, schooling, and socioeconomic characteristics of the children's families. The sample consisted of 5702 children aged 8–9 years, including 50.2% girls. In multivariate logistic regression models, children's sleeping difficulties were associated with children's abnormal symptoms of both hyperactivity-inattention (adjusted Odds Ratio (aOR) 2.05; 95% Confidence Interval 1.70–2.47) and emotional symptoms (aOR 5.34; 95% CI 4.16–6.86). Factors specifically associated with abnormal hyperactivity/inattention were: male sex (aOR 2.29; 95% CI 1.90–2.76), access to specialized care prior to the pandemic and its suspension during school closure (aOR 1.51; 95% CI 1.21–1.88), abnormal emotional symptoms (aOR 4.06; 95% CI 3.11–5.29), being unschooled or schooled with assistance before lockdown (aOR 2.13; 95% CI 1.43–3.17), and tutoring with difficulties or absence of a tutor (aOR 3.25; 95% CI 2.64–3.99; aOR 2.47; 95% CI 1.48–4.11, respectively). Factors associated with children's emotional symptoms were the following: being born pre-term (aOR 1.34; 95% CI 1.03–1.73), COVID-19 cases among household members (aOR 1.72; 95% CI 1.08–2.73), abnormal symptoms of hyperactivity/inattention (aOR 4.18; 95% CI 3.27–5.34) and modest income (aOR 1.45; 95% CI 1.07–1.96; aOR 1.36; 95% CI 1.01–1.84). Multiple characteristics were associated with elevated levels of symptoms of hyperactivity-inattention and emotional symptoms in children during the period of school closure due to COVID-19. Further studies are needed to help policymakers to balance the pros and cons of closing schools, taking into consideration the educational and psychological consequences for children. [ABSTRACT FROM AUTHOR]

Background: The risk of drug-drug interactions (DDI) has become a major issue in cancer patients. However, data in sarcoma patients are scarce. We aimed to evaluate the frequency and the factors associated with DDI with antitumor treatments, and to evaluate the impact of a pharmacist evaluation before anticancer treatment.Patients and Methods: We performed a retrospective review of consecutive sarcoma patients starting chemotherapy (CT) or Tyrosine kinase inhibitor (TKI). A pharmacist performed medication reconciliation and established an early toxicity risk assessment. Potential DDI with antitumor drugs were identified using Micromedex electronic software.Results: One hundred and twenty-two soft-tissue and 80 bone sarcoma patients (103 males, median age 50 years,) were included before CT (86%) or TKI (14%). The median number of medications was 3; 34 patients (22% of patients with medication reconciliation) reported complementary medicine use. 37 potential DDI classified as major, were identified (12% of the 243 pre-therapeutic assessments). In multivariate analysis, TKI (p < 0.0001), proton pump inhibitor (p = 0.026) and antidepressant (p < 0.001) were identified as risk factors of DDI (p < 0.02). Only marital status (p = 0.003) was associated with complementary medicine use. A pharmacist performed 157 medication reconciliations and made 71 interventions among 59 patients (37%). In multivariate analysis, factors associated with pharmacist intervention were: complementary medicines (p = 0.004), drugs number (p = 0.005) and treatment with TKI (p = 0.0002) CONCLUSIONS: Clinical interventions on DDI are more frequently required among sarcoma patients treated with TKI than CT. Multidisciplinary risk assessment including a medication reconciliation by a pharmacist could be crucial to prevent DDI with TKI. [ABSTRACT FROM AUTHOR]

Micronodular thymic carcinoma with lymphoid hyperplasia (MNTCLH) is a rare form of thymic carcinoma. We present the experience of RYTHMIC, the French national network devoted to the treatment of thymic epithelial tumors through multidisciplinary tumor boards with a review of all tumors by pathologists for classification and staging. Six cases of MNTCLH were diagnosed during a review of 1007 thymic epithelial tumors. Histologically, epithelial cells with atypia and mitoses formed micronodules that were surrounded by an abundant lymphoid background with follicles. There was neither obvious fibro-inflammatory stroma nor necrosis. Spindle cells areas were common. Initial diagnosis was micronodular thymoma in two cases, cellular atypia being overlooked, eclipsed by the micronodular pattern. Immunohistochemistry with a panel of five antibodies showed that cytokeratins (AE1-AE3) and p63-positive epithelial cells also expressed CD5 and that there was no TdT-positive cells within the tumors. CD20 highlighted the lymphoid hyperplasia. Additionally epithelial cells also expressed CD117 and diffusely Glut 1. Twenty-seven micronodular thymomas with lymphoid stroma diagnosed during the same period did not show the CD5 and CD117 positivities seen in MNTCLH and contained TdT-positive lymphocytes. Three of the 6 patients with MNTCLH had adjuvant radiotherapy. Three patients with follow-up information were alive without recurrence at 38, 51, and 95 months. Our study shows that immunohistochemistry, such as that used in the RYTHMIC network with a small panel of antibodies, may easily help to confirm the correct diagnosis of MNTCLH, a rare and low-aggressive form of thymic carcinoma, and avoid the misdiagnosis of micronodular thymoma. [ABSTRACT FROM AUTHOR]

Background: The Patient Reported Outcome Measurement Information System profile instruments include "high information" items drawn from large item banks following the application of modern psychometric criteria. The shortest adult profile, PROMIS-29, looks set to replace existing short-form instruments in research and clinical practice. The objective of this study was to undertake the first psychometric evaluation of the Norwegian PROMIS-29, following a postal survey of a random sample of 12,790 Norwegians identified through the National Registry of the Norwegian Tax Administration. Confirmatory factor analysis was used to assess structural validity. Fit to the Rasch partial credit model and differential item functioning (DIF) were assessed in relation to age, gender, and education. PROMIS-29 scores were compared to those for the EQ-5D-5L and the Self-assessed Comorbidity Questionnaire (SCQ), for purposes of assessing validity based on a priori hypotheses. Results: There were 3200 (25.9%) respondents with a mean age (SD) of 51 (20.7, range 18 to 97 years) and 55% were female. The PROMIS-29 showed satisfactory structural validity and acceptable fit to Rasch model including unidimensionality, and measurement invariance across age and education levels. One pain interference item had uniform DIF for gender but splitting gave satisfactory fit. Domain reliability estimates ranged from 0.85 to 0.95. Correlations between PROMIS-29 domain, SCQ and EQ-5D scores were largely as expected, the largest being for scores assessing very similar aspects of health. Conclusions: The Norwegian version of the PROMIS-29 is a reliable and valid generic self-reported measure of health in the Norwegian general population. The instrument is recommended for further application, but the analysis should be replicated and responsiveness to change assessed in future studies before it can be recommended for clinical and health services evaluation in Norway. [ABSTRACT FROM AUTHOR]

Purpose: [18F]-2-Fluoro-2-deoxy-D-glucose PET/CT (FDG PET/CT) is a sensitive and quantitative technic for detecting inflammatory process. Glucose uptake is correlated with an increased anaerobic glycolysis seen in activated inflammatory cells such as monocytes, lymphocytes, and granulocytes. The aim of the study was to assess the inflammatory status at the presumed peak of the inflammatory phase in non-critically ill patients requiring admission for COVID-19. Methods: Patients admitted with COVID-19 were prospectively enrolled. FDG PET/CT was performed from day 6 to day 14 of the onset of symptoms. Depending on FDG PET/CT findings, patients' profiles were classified as "inflammatory" or "low inflammatory." FDG PET/CT data were compared with chest CT evolution and short-term clinical outcome. All inflammatory sites were reported to screen potential extra-pulmonary tropism. Results: Thirteen patients were included. Maximum standardized uptake values ranged from 4.7 to 16.3 in lungs. All patients demonstrated increased mediastinal lymph nodes glucose uptake. Three patients (23%) presented mild nasopharyngeal, two patients (15%) bone marrow, and five patients (38%) splenic mild increase in glucose uptake. No patient had significant digestive focal or segmental glucose uptake. There was no significant physiological myocardial glucose uptake in all patients except one. There was no correlation between PET lung inflammatory status and chest CT evolution or short-term clinical outcome. Conclusion: Inflammatory process at the presumed peak of the inflammatory phase in COVID-19 patients is obvious in FDG PET/CT scans. Glucose uptake is heterogeneous and typically focused on lungs. Trial registration: NCT04441489. Registered 22 June 2020 (retrospectively registered). [ABSTRACT FROM AUTHOR]

Purpose: The widespread use of Nivolumab results in an increasing number of side effects and adverse events. Herein, we evaluated the impact of Nivolumab on crude and normalized pulmonary artery diameter (PAD).Methods: We analyzed clinical, morphometric, pathological and radiological data of lung cancer patients treated by Nivolumab in an 18-month period. Blinded radiological evaluation was performed, by three observers measuring axial PAD and Aorta diameter (AoD) in secondarily matched pre- and post-Nivolumab CT-scans. Correlation between ΔPAD and clinicopathological data was investigated.Results: 59 patients receiving Nivolumab for treatment of advanced lung carcinoma were identified. Pre-and post-Nivolumab comparison of CT-scan measures revealed that mean PAD was 26.3 ± 2.8 mm versus 28.0 ± 3.0 mm (p < 0.001), and mean PAD/AoD ratio was 0.82 ± 0.09 versus 0.87 ± 0.11 (p <  0.001), respectively. Median ΔPAD was 0.05 [0.01-0.122] was significantly higher in hypometabolic patients exhibiting low Rest Energy Expenditure (p = 0.03). Patients exhibiting ΔPAD > 1% had significantly lower serum albumin level (p = 0.03), and higher nutritional risk (p = 0.02), compared to others. Unlike Nivolumab therapy, there was no increase of PAD after chemotherapy in the same cohort of patients with available scans (n = 45, 25.9 ± 2.9 mm pre-chemotherapy versus 25.7 ± 2.4 mm post-chemotherapy, p = 0.51). Anti-PD-1 treatment was associated with immune-related adverse events in 11 (18.6%) cases including 2 cases of life-threatening acute pulmonary hypertension, both exhibiting post-treatment PAD/AoD ratio > 1.Conclusion: Nivolumab is associated to PAD enlargement, a potential marker of pulmonary hypertension, sometimes leading to lethal adverse events. Careful CT-scan and echocardiographic evaluation of PAD should be part of the therapeutic work-up of patients receiving Nivolumab, especially those suffering cancer-associated malnutrition. [ABSTRACT FROM AUTHOR]

Purpose: Weaning failure from mechanical ventilation may be due to lung de-recruitment or weaning-induced pulmonary oedema (WIPO). Both can be diagnosed by lung ultrasound (LUS) and transthoracic echocardiography (TTE), respectively. We conducted a prospective observational study, combining TTE and LUS, to determine if LUS alone may identify elderly patients at high risk of weaning or extubation failure.Methods: Before and at the end of spontaneous breathing trials (SBT) in 40 elderly patients, we prospectively performed LUS and TTE. Extubation was decided by an independent operator. LUS included global and anterolateral LUS score. TTE included measurement of E/A and E/Ea ratios to determine LV filling pressures. SBT LUS scores for prediction of weaning outcome and for the diagnosis of WIPO were studied.Results: Weaning or extubation failure was observed in 45% (95% CI 28-61) of patients. ROC analysis for ability of global SBT LUS to predict weaning/extubation failure and extubation failure found AUC of 0.80 and 0.81, respectively. AUC for anterolateral SBT LUS to predict weaning/extubation failure and extubation failure was 0.79 and 0.81, respectively. Increased LV filling pressure during SBT was observed without increase of anterolateral LUS score. Inversely, increase of anterolateral LUS was observed without increased filling pressure and was associated with extubation failure. Global and anterolateral SBT LUS were not correlated to E/Ea.Conclusion: In elderly patients, global and anterolateral LUS scores were associated with weaning and extubation failures while echocardiographic indices of filling pressures were not.Clinical Trial Number and Registry Url: ClinicalTrials.gov No. NCT03261440. [ABSTRACT FROM AUTHOR]

Introduction: The use of rotating-hinge total knee arthroplasties (TKA), despite several developments in prosthetic design, remains controversial. Results as well as indications of these devices are still discussed in primary intention and for young patients. The aim was to analyze early complications and survival rate of rotating-hinge TKA in primary intention and for revisions.Methods: A retrospective study included all the patients operated for primary or revision TKA procedure using a rotating-hinge TKA between 2015 and 2018. Clinical and radiological data were collected before surgery and then at a minimum follow-up of 1 year. The primary endpoint was the aseptic revision-free survival rate. Secondary endpoints were the overall survival rate, IKS scores, range of motion and patellar complications.Results: Forty patients were included at an average follow-up of 18 months. Primary implantation was performed for 12 patients (30%), and revision for 28 cases (70%). At a mean follow-up of 18 months, only one implant was removed for a septic cause. The cumulative survival rate at 24 months was 95%. At final review, eight knees (20%) had been revised, five (12.5%) due to infection, two (5%) because of extensor mechanism failure, two (5%) for global stiffness. The objective and subjective IKS were significantly higher postoperatively in both primary and revision groups (p < 0.0001). Patellar height was significantly smaller after revision (p = 0.04), while ROM significantly improved in this group (p = 0.02). At final endpoint, one implant was removed for a septic cause.Conclusion: This rotating-hinge TKA provides satisfying clinical and functional outcomes in primary intentions and in revision cases. There was no implant-associated complication. The complication rate remains high for revision surgery cases, mostly due to previous joint infections and poor soft tissue quality causing extensor mechanism failure. A longer-term study should be conducted to confirm this trend. [ABSTRACT FROM AUTHOR]

Introduction: Tibiofemoral dislocation is the most serious form of instability following total knee arthroplasty (TKA). It is little reported in the literature, despite severity comparable to that in the native knee. The present systematic review and meta-analysis aimed to identify risk factors and treatment strategies.Methods: The Cochrane, Medline (via PubMed), Google, and PROSPERO data-bases were searched in January 2018 following the PRISMA meta-analysis guidelines. All articles referring to tibiofemoral dislocation following primary TKA were included for analysis and extraction of individual data. Study data comprised age, gender, comorbidities, primary and revision implant design, aetiology, and treatment strategy.Results: Individual data for 57 patients (23 studies) were analyzed. A total of 62.0% of primary implants were posterior-stabilized (49 patients) and 30.4% posterior-cruciate-retaining (24 patients). Obesity was the most frequent comorbidity (39.2%; 31 patients), followed by severe pre-operative deformity (31.6%; 25 patients). Aetiologies of dislocation were mainly related to comorbidity (15 studies; 65.2%) or intra-operative iatrogenic destabilization (14 studies; 60.9%). Non-operative treatment (splint) after dislocation was associated with high rates of recurrence (39.1%) but significantly fewer complications (p = 0.033). Implant revision surgery (45 patients; 80.4%) usually involved higher-constraint models (31 patients; 70.8%).Conclusions: Improved implant design has reduced the rate of tibiofemoral dislocation, although this complication remains serious in both the short and the long term. The present review identified patient- and surgeon-related risk factors. Awareness of the former, which are identifiable pre-operatively, and of the most frequent technical errors is critical. [ABSTRACT FROM AUTHOR]

Purpose: The use of adjuvant radiation in the treatment of soft-tissue sarcoma (STS) is equivocal in selected cases. Our objective was to compare the short-term outcomes in patients operated on for a local recurrence who had radiation for the primary tumour to those who were spared radiation.Methods: This was a retrospective study of 103 patients treated for a local recurrence: 48 (47%) with previous radiation and 55 (53%) without. Our primary outcome criterion was to identify the differences in the local treatment provided. Secondary outcomes were the cumulative incidence of a surgical site infection/wound complication (SSI/WC), variables associated with SSI/WC, and local recurrence.Results: Amputation and the incidence of re-operation were significantly more frequent in patients who received previous radiation compared to patients without previous radiation (27% vs 9%, p = 0.02, for amputation; 26% vs 36% at 2 years for SSI/WC, p = 0.049). Multivariable regression models found previous radiation (p = 0.049), arteriopathy (p = 0.012), location at lower limb (p = 0.09), and use of a flap (0.0048) associated with the risk of SSI/WC.Conclusions: Previous radiation is associated with an increased risk of amputation and reoperation for SSI/WC when treating a local recurrence. This information should be accounted for when deciding for the use of radiation. [ABSTRACT FROM AUTHOR]

Purpose: Sepsis and non-septic systemic inflammatory response syndrome (SIRS) are the same syndromes, differing by their cause, sepsis being secondary to microbial infection. Microbiological tests are not enough to detect infection early. While more than 50 biomarkers have been proposed to detect infection, none have been repeatedly validated.Aim: To assess the accuracy of circulating biomarkers to discriminate between sepsis and non-septic SIRS.Methods: The CAPTAIN study was a prospective observational multicenter cohort of 279 ICU patients with hypo- or hyperthermia and criteria of SIRS, included at the time the attending physician considered antimicrobial therapy. Investigators collected blood at inclusion to measure 29 plasma compounds and ten whole blood RNAs, and-for those patients included within working hours-14 leukocyte surface markers. Patients were classified as having sepsis or non-septic SIRS blindly to the biomarkers results. We used the LASSO method as the technique of multivariate analysis, because of the large number of biomarkers.Results: During the study period, 363 patients with SIRS were screened, 84 having exclusion criteria. Ninety-one patients were classified as having non-septic SIRS and 188 as having sepsis. Eight biomarkers had an area under the receiver operating curve (ROC-AUC) over 0.6 with a 95% confidence interval over 0.5. LASSO regression identified CRP and HLA-DRA mRNA as being repeatedly associated with sepsis, and no model performed better than CRP alone (ROC-AUC 0.76 [0.68-0.84]).Conclusions: The circulating biomarkers tested were found to discriminate poorly between sepsis and non-septic SIRS, and no combination performed better than CRP alone. [ABSTRACT FROM AUTHOR]

Background: Health literacy is a key asset, defined as the capacity to acquire, understand and use information in ways which promote and maintain good health. Objectives: To assess the reliability and validity of the French translation of the Functional, Communicative and Critical Health Literacy (FCCHL) scale. Methods/participants: A cross-sectional survey using an online questionnaire was proposed to all members of Seintinelles association. Exploratory and confirmatory factorial analyses were conducted. Results: Data from 2342 respondents (45.8% had cancer history) were analysed. The FCCHL scale was well-accepted (missing value by item ≤0.7%). Factor analysis revealed an acceptable fit of three-factor model (comparative fit index = 0.922, root mean square error of approximation = 0.065 and standardized root mean square residual = 0.052). The FCCHL showed satisfactory reliability (α = 0.77) and scalar invariance was reached for education and deprivation, but not for age. Known group validity was verified as mean scale scores differed according to education, deprivation and age, as expected. Conclusion: The French version of the FCCHL provides a brief reliable and valid measure to explore the dimensions of health literacy. It could be used by health professionals to screen for health literacy level in order to develop this skill and to tailor health communication. [ABSTRACT FROM AUTHOR]

Little is known on factors predicting toxicity of anti-PD1 checkpoint inhibitors. Sarcopenic obesity is associated with increased acute toxicity of cytotoxic agents and targeted therapies. We explored whether body composition also influenced the occurrence of early acute limiting toxicity (ALT) of anti-PD1 in melanoma patients. This is a monocentric, retrospective study analyzing toxicity outcome in consecutive melanoma patients treated with nivolumab or pembrolizumab. Various parameters linked to the patient or the disease status have been analysed. Body mass index (BMI; kg/m) and muscle mass using CT were measured prior to treatment initiation. Chi-squared test and Mann-Whitney's tests were used for the comparison of categorical and continuous variables respectively. Among 68 melanoma patients treated with anti-PD1 (47 pembrolizumab, 21 nivolumab), 38 (56%) patients had a BMI ≥ 25 kg/m and 11 (16%) a BMI ≥ 30, while 13 (19%) had both sarcopenia and a BMI ≥ 25 kg/m. For the 11 (16%) patients who experienced early ALT, the mean BMI was higher (27.9 versus 24.7 kg/m; p = 0.04). Among the 32 female patients, sarcopenic overweight patients had a 6.5-fold increased risk of ALT (50 versus 7.7%; p = 0.01). Sarcopenic overweight is associated with more early ALT of anti-PD1 in melanoma patients. [ABSTRACT FROM AUTHOR]

Purpose: Carboplatin clearance is correlated with glomerular filtration rate (GFR) and usually estimated with creatinine clearance using Cockcroft-Gault (CG) formula. Because plasma creatinine level is highly correlated with muscle mass, we hypothesized that an abnormal body composition with a low lean body mass (LBM) percentage [(LBM/weight) × 100] may result in inadequate carboplatin dosing. Serum cystatin C is an alternative marker of GFR, not affected by muscle mass. We aimed to investigate the influence of total LBM and LBM percentage on GFR calculation, using creatinine (CrCl) or cystatin C (GFRcysC-creat) in cancer patients.Methods: Pretreatment serum creatinine and cystatin C were prospectively measured in consecutive patients. CrCl (CG formula), GFRcysC-creat (CKD-EPI creatinine-cystatin equation), and LBM (CT scan) were calculated. Severe thrombocytopenia post-carboplatin were analyzed.Results: In 131 patients without renal insufficiency, LBM was correlated with creatinine (r = 0.30, p < 0.005) but not with cystatin C (r = -0.07, p = 0.43). In patients with the lowest LBM percentage, the CrCl was significantly higher than GFRcysC-creat indicating an overestimation of GFR with creatinine (p = 0.0004). In 24 patients treated with carboplatin AUC 5 (mg/ml min) ± paclitaxel, the risk of severe thrombocytopenia was associated with lower LBM percentage (p = 0.0002) and higher CrCl/GFRcysC-creat ratio (p = 0.006). By ROC analysis, the CrCl/GFRcysC-creat ratio threshold predicting severe thrombocytopenia was 1.23.Conclusions: A low LBM percentage increases the risk of inadequate GFR calculation by CG formula, and carboplatin overdosage with severe thrombocytopenia. High CrCl/GFRcysC-creat ratio allows the identification of these patients. [ABSTRACT FROM AUTHOR]

Purpose: Abiraterone acetate combined with prednisone improves survival in metastatic castration-resistant prostate cancer (mCRPC) patients. This oral anticancer agent may result in drug-drug interactions (DDI). We aimed to evaluate the prevalence of DDI with abiraterone and the possible determinants for the occurrence of these DDI.Methods: We performed a single centre retrospective review from electronic medical records of mCRPC patients treated with abiraterone from 2011 to 2015. Potential DDI with abiraterone were identified using Micromedex and were categorized by a 4-point scale severity.Results: Seventy-two out of ninety-five mCRPC pts (median age: 77 years [68-82]) had comorbidities. The median number of drugs used per patient was 7 [5-9]. 66 potential DDI with abiraterone were detected in 49 patients (52%): 39 and 61% were classified as major and moderate DDI, respectively. In the univariate analysis, pain (p < 0.0001), hypo-albuminemia (p = 0.032), and higher ECOG performance status (PS) (p = 0.013) were significantly associated with a higher risk of DDI with abiraterone. Pain (p < 0.0001) and PS (p = 0.018) remained significant in the multivariate analysis.Conclusions: Polypharmacy is an issue among mCRPC patients. In our study, half of the patients have potential DDI with abiraterone. Patients with pain and poor PS are at higher risk of DDI with abiraterone. A medication review by a pharmacist is of crucial importance to prevent DDI with abiraterone. [ABSTRACT FROM AUTHOR]

Background Older non-small cell lung cancer (NSCLC) patients under erlotinib are reported to experience more acute toxicity. We hypothesized that modifications in erlotinib pharmacokinetics might explain this observation. Methods A monocentric prospective clinico-pharmacological study included stage IIIb/IV NSCLC consecutive pts. treated with erlotinib. The plasma concentration of erlotinib (Ce) was measured at steady state on day 15. We studied the relationship between age > 75 years, and Ce, using the Mann-Whitney U test and with the occurrence of acute toxicity, using a Fisher's test. Results A total of 53 pts. were analyzed. Median age was 68 years (31-83), 56 % were female. All pts. > 75 years experienced toxicity: all grade acute adverse events were 1.6 fold more frequent (100 % vs 61 %; OR 95 % CI [1.9-INF]; p = 0.003). At day 15, Ce increased with age. Over 75 years old, the mean Ce was 1.5 fold higher: 2091 ng/mL (95 % CI [1476; 2706]) vs 1359 (95 % CI [1029; 1689]; p = 0.024). In pts. over 80 years old, the mean Ce was doubled: 2729 (95 % CI [1961; 3497]) vs 1358 ng/mL (95 % CI [1070; 1646]; p = 0.0019). Reduced lean body mass over 75 years (median 36.6 kg versus 49.1 kg) might account for these differences. Finally, the risk of early erlotinib discontinuation was increased by 11 in older pts. (33 % vs 3 % OR 17.2; 95 % CI [1.7; 892.5] p = .005). Conclusion The risk of overexposure to erlotinib increases with age. Reduced lean body mass may explain erlotinib pharmacokinetics and excessive acute toxicity in the elderly. [ABSTRACT FROM AUTHOR]

Background: Duodenal stenosis is one of the most common causes of failed ERCP for obstructive jaundice. Alternative approaches include anterograde biliary drainage, with higher morbidity. We report in this study the efficacy and safety of temporary placement of a covered duodenal self-expandable metal stent (cSEMS) in order to access the papilla and achieve secondary retrograde biliary drainage in patients with obstructive jaundice and failed ERCP due to concomitant duodenal stenosis.Methods: From June 2006 to March 2014, a total of 26 consecutive patients presenting obstructive jaundice without severe sepsis with failed ERCP due to duodenal invasion were enrolled. A temporary 7-day duodenal cSEMS was placed during the failed ERCP, and a second ERCP was attempted at day 7 after duodenal stent removal.Results: Duodenal cSEMS placement and retrieval were technically successful in all cases. Access to the papilla at day 7 was possible in 25 cases (96 %, 95 % CI 80-99 %). Secondary successful ERCP was achieved in 19 cases (76 %, 95 % CI 55-91 %, i.e., 73 %, 95 % CI 73-86 %, in an intention-to-treat analysis). Mean bilirubin level was 102 ± 90 µmol/L at baseline rising to 164 ± 121 µmol/L at day 7. There were 6 stent migrations and no adverse events recorded between the two ERCPs.Conclusions: When ERCP for obstructive jaundice fails due to duodenal invasion, temporary cSEMS placement offers a safe and effective way to achieve successful secondary ERCP while avoiding riskier endoscopic ultrasound or percutaneous transhepatic anterograde biliary drainage. [ABSTRACT FROM AUTHOR]

Although lung cancer patients harboring EGFR mutations benefit from treatment with EGFR-tyrosine kinase inhibitors ( EGFR- TKI), most of them rapidly relapse. RHOB GTPase is a critical player in both lung carcinogenesis and the EGFR signaling pathway; therefore, we hypothesized that it could play a role in the response to EGFR- TKI. In a series of samples from EGFR-mutated patients, we found that low RHOB expression correlated with a good response to EGFR- TKI treatment while a poor response correlated with high RHOB expression (15.3 versus 5.6 months of progression-free survival). Moreover, a better response to EGFR- TKI was associated with low RHOB levels in a panel of lung tumor cell lines and in a lung-specific tetracycline-inducible EGFRL858R transgenic mouse model. High RHOB expression was also found to prevent erlotinib-induced AKT inhibition in vitro and in vivo. Furthermore, a combination of the new-generation AKT inhibitor G594 with erlotinib induced tumor cell death in vitro and tumor regression in vivo in RHOB-positive cells. Our results support a role for RHOB/ AKT signaling in the resistance to EGFR- TKI and propose RHOB as a potential predictor of patient response to EGFR- TKI treatment. [ABSTRACT FROM AUTHOR]

Aircraft parabolic flights repetitively provide up to 23 seconds of reduced gravity during ballistic flight manoeuvres. Parabolic flights are used to conduct short microgravity investigations in Physical and Life Sciences and in Technology, to test instrumentation prior to space flights and to train astronauts before a space mission. The use of parabolic flights is complementary to other microgravity carriers (drop towers, sounding rockets), and preparatory to manned space missions on board the International Space Station and other manned spacecraft, such as Shenzhou and the future Chinese Space Station. After 17 years of using the Airbus A300 ZERO-G, the French company Novespace, a subsidiary of the ' Centre National d'Etudes Spatiales' (CNES, French Space Agency), based in Bordeaux, France, purchased a new aircraft, an Airbus A310, to perform parabolic flights for microgravity research in Europe. Since April 2015, the European Space Agency (ESA), CNES and the ' Deutsches Zentrum für Luft- und Raumfahrt e.V.' (DLR, the German Aerospace Center) use this new aircraft, the Airbus A310 ZERO-G, for research experiments in microgravity. The first campaign was a Cooperative campaign shared by the three agencies, followed by respectively a CNES, an ESA and a DLR campaign. This paper presents the new Airbus A310 ZERO-G and its main characteristics and interfaces for scientific experiments. The experiments conducted during the first European campaign are presented. [ABSTRACT FROM AUTHOR]

Background: Duodenal covered self-expandable metal stent (cSEMS) can be used in malignant or benign gastroduodenal obstruction. The need for biliary stenting in patients with no concomitant biliary stricture, before duodenal cSEMS placement, remains unknown. The aim of this study was to determine whether cSEMS placement is responsible for biliary obstruction.Methods: This is a single-center, retrospective, case-controlled study, including 106 patients with symptomatic gastric outlet obstruction or duodenal fistula who received a covered nitinol duodenal stent by using through-the-scope/over-the-wire placement procedure. The main outcome measurement was the occurrence comparison of jaundice and bilirubin level, between patients with previous or concomitant biliary stenting (cSEMS + BS group), and patients with no biliary stent (cSEMS group) during an observational period of 90 days.Results: Hundred and six patients underwent cSEMS placement between June 2005 and March 2014: 53 in the cSEMS group (58% male, mean age 66.4 ± 13.3 years) and 53 in cSEMS + BS group (60% male, mean age 70.4 ± 11.6 years). The obstruction was due to cancer in 45% in cSEMS group and 87% in cSEMS + BS group. No case of jaundice was reported in the cSEMS group or in the cSEMS + BS group. In cSEMS group, the mean bilirubin level (μmol/L ± SD) was 8.0 ± 4 at baseline and 8.5 ± 4.6 at day 10, while in the cSEMS + BS group it was 91.4 ± 108 at baseline and 35.3 ± 39 at day 10 (p < 0.01). Patients from the two groups were matched on age, gender and bilirubin level at baseline. Evolution of bilirubinemia was +0.98 ± 2.76 µmol/L in experimental group and +0.39 ± 522 µmol/L in the control group (p = 0.34). No significant difference was observed between the two groups in term of technical success, clinical effectiveness, migration and other complications.Conclusions: Previous biliary stenting is not required before endoscopic covered duodenal stent placement in patients with no associated biliary obstruction. Prospective studies are needed. [ABSTRACT FROM AUTHOR]

Purpose: Pegylated liposomal doxorubicin (PLD) is widely used in relapsing ovarian carcinoma. Its original formulation is metabolized by the monocyte-macrophage system. One of its main toxicities is the palmoplantar erythrodysesthesia (PPE) syndrome. To date, no predictive factors of PPE have been identified.Methods: Data of patients (pts) treated with PLD between 2005 and 2014 were retrospectively collected. A case-control study was performed, comparing main baseline clinical and biological characteristics of pts experiencing PPE and those who did not, after at least three cycles of PLD. A pilot analysis of blood monocyte subpopulations (classical, intermediate and non-classical) was performed by FACS in selected pts.Results: Among 88 pts treated with PLD, 28 experienced PPE of any grade (31, 95 % CI 21-41). The first occurrence of PPE was at first cycle in only 11 % of pts, peaked at cycle 2 (32 %) and represented 57 % of cases after cycle 3. Baseline characteristics of pts with PPE were compared to 27 control pts who received at least 3 cycles. Older pts represented 61 % of pts with PPE and 15 % of pts without PPE (p = 0.04 by Chi-square test). Monocyte count and inflammatory parameters were not associated with PPE. However, the analysis of monocyte subpopulations revealed a large inter-patient variability.Conclusion: Contrary to most acute toxicities, PPE occurred more frequently after several cycles, suggesting a PLD body accumulation through repeated cycles. PPE was more frequent in pts older than 70 years. Monocyte subpopulations may have different roles on PLD metabolism and warrant further studies. [ABSTRACT FROM AUTHOR]

Introduction Sunitinib is a multikinase inhibitor active in various cancers types including renal cancers and endocrine tumors. The study analyzed the influence of the lean body mass (LBM) and of pharmacogenetic variants on the exposure to sunitinib and its active metabolite, SU12662, and on sunitinib toxicity and clinical activity. Materials and Methods Exposure to sunitinib and SU12662 was assessed on days 10 and 21 during the first treatment cycle. Acute toxicity was graded using the NCI 4.0 CTCAE ver. 4.0. The LBM and 14 common single nucleotide polymorphisms in the CYP3A4/3A5, NR1I2, NR1I3, ABCB1, and ABCG2 genes were analyzed according to the drug exposure at day 10. Determinants (including sunitinib exposure and pharmacogenetic variants) for toxicities were assessed, as well as the relationship between drug exposure and survival in renal cancer patients. Results Ninety-two patients (60 % with renal cancer) were assessable for pharmacokinetics, toxicity and survival, and 66 for genetic analysis. The LBM ( p < 0.0001) and a polymorphism in the ABCG2 transporter (421C>A) ( p = 0.014) were two independent parameters accounting for the variability of composite (sunitinib + SU12662) exposure. Advanced age (OR = 1.47 [1.01-2.15], p = 0.048) and high sunitinib exposure (OR = 1.16 [1.05-1.28], p = 0.005) were independently associated with any grade ≥ 3 acute toxicity, and high SU12662 exposure was associated with grade ≥ 2 thrombocytopenia (OR = 1.27 [1.03-1.57], p = 0.028). A high composite area under the curve (AUC) >1,973 ng/mL∙h at day 21 was associated with a doubled survival (35.2 vs 16.7 months; log-rank p = 0.0051) in renal cancer patients. Conclusions This study indicates that LBM and drug monitoring may be helpful in the management of sunitinib-treated patients. [ABSTRACT FROM AUTHOR]

Combining functionalities in devices with high performances is a great challenge that rests on the discovery and optimization of materials. In this framework, layered oxides are attractive for numerous purposes, from energy conversion and storage to magnetic and electric properties. We demonstrate here the oxygen storage ability of ferroelectric LuFe2O4+x within a large x range (from 0 to 0.5) and its cycling possibility. The combination of thermogravimetric analyses, X-ray diffraction and transmission electron microscopy evidences a complex oxygen intercalation/de-intercalation process with several intermediate metastable states. This topotactic mechanism is mainly governed by nanoscale structures involving a shift of the cationic layers. The ferrite is highly promising because absorption begins at a low temperature (), occurs in a low oxygen pressure and the uptake of oxygen is reversible without altering the quality of the crystals. The storage/release of oxygen coupled to the transport and magnetic properties of LnFe2O4 opens the door to new tunable multifunctional applications. [ABSTRACT FROM AUTHOR]

Several groups have published flow cytometry scores useful for the diagnosis or prognosis of myelodysplastic syndromes (MDS), mainly based on the detection of immunophenotypic abnormalities in the maturation of granulocytic/monocytic and lymphoid lineages. As anemia is the most frequent symptom of early MDS, the aim of this study was to identify markers of dyserythropoiesis relevant for the diagnosis of MDS analyzed by selecting erythroblasts in a whole no-lysis bone marrow strategy by using a nuclear dye. This prospective study included 163 patients, including 126 with cytopenias leading to MDS suspicion and 46 controls without MDS. In a learning cohort of 53 unequivocal MDS with specific markers, there was a significant difference between the coefficients of variation of mean fluorescence intensities of CD71 and CD36 in MDS patients compared with controls. These two parameters and the hemoglobin level were used to build a RED-score strongly suggestive of MDS if 3. Using the RED-score in the whole cohort, 80% of MDS or non-MDS patients were correctly classified. When combined with the flow score described by Ogata et al., this strategy allowed to reach a very high sensitivity of 88% of patients correctly classified. [ABSTRACT FROM AUTHOR]