Search

Despite the feminization of the medical workforce, women do not have the same career perspectives as men. In nuclear medicine, little information is available on the gender gap regarding prominent author positions of scientific articles. Therefore, the purpose of this study was to evaluate recent trends in the gender distribution of first and last authorship of articles published in nuclear medicine journals. Methods: We conducted a bibliometric analysis of first and last author gender of articles published from 2014 to 2020 in 15 nuclear medicine journals. Manuscript title, article type, journal impact factor, date of publication, first and last name and country of provenance of first and last authors were noted. The Gender-API software was used to determine author gender. All statistics were descriptive. Results: Women represented 32.8% of first authors and 19.6% of last ones. Female authorship increased from 28.2% (428 of 1518 articles) in 2014 to 35.5% (735 of 2069 articles, relative increase 72%) in 2020 (p

Background The outcome of lung transplantation (LT) is correlated with donor selection. A donor age of 65 years is classically considered a contraindication to lung procurement, and the results of LT from elderly donors remain to be established. Methods This was a retrospective study of a prospectively maintained database including all LTs performed in a single institution (Bichat Hospital, University of Paris, Paris, France) from January 2014 to March 2019. Donors65 years of age or older were included in the elderly group, whereas donors younger than 65 years of age were included in the control group. Results The study group included 241 LTs, including 44 (18%) in the elderly group and 197 (82%) in the control group. As compared with the control group, the elderly group was characterized by the following: donors of shorter stature (166 cm vs 172 cm; P = .04) and with less smoking history (14% vs 40%; P = .001), less bronchoscopic abnormality (20% vs 36%; P = .042), and less chest opacity (16% vs 30%; P = .048); and recipients of shorter stature (166 cm vs 170 cm; P = .04) but with similar diagnoses and gravity. There was no significant difference between the groups in any of the outcomes studied, including primary graft dysfunction, 30-day mortality, 1-year survival, chronic lung allograft dysfunction–free survival, and overall survival. In univariate analysis, the Oto lung donor score was the only factor associated with 1-year survival (score of 6 in alive patients vs score of 7 in dead patients; P = .04); donor age 65 years old or older was not. Conclusions Carefully selected lung grafts from donors 65 years of age or older are associated with outcomes similar to those reported with grafts from younger donors Grafts from older donors thus provide an interesting option to expand the donor pool during a shortage.

A multiplexed electrochemical platform has been designed for electrochemical screening applications, such as bacteria detection. It includes 16x16 electrochemical cell array in a two-electrode mode fabricated by a combination of screen printing, inkjet printing, and flash-light sintering techniques wherein each cell is addressed sequentially by a portable multiplexer potentiostat. This multiplexer unit is capable of making a total of 256 independent voltametric measurements that were validated by performing cyclic voltammetry in two-electrode mode using four different redox mediators: [Fe(CN)(6)](3-)/(4-), FcMeOH, Ru[(NH3)(6)]Cl-3 and K-2[IrCl6]. The smart design and the use of mass production techniques makes the multiplexer device applicable for numerous electrochemical applications including health, food, and environmental monitoring.

Objectives Preparation of injectable anticancer drugs in hospital pharmacies, in particular of cytotoxics, is a high-risk activity. We used Preliminary Risk Analysis (PRA) to analyse the risks in the different steps of our anticancer drug circuit, including the preparation step (PRA1). Then, to prepare an important change in management of the circuit with the software Chimio® (pooling of three databases for subcontracting), we repeated the analysis of preparation step (PRA2). PRA is known to be time and resource consuming. To overcome this, we developed a strict organisational framework to perform the analysis within a reasonable amount of time. We present the PRA method including its practical implementation, and its application to the anticancer drug preparation process, before and after pooling of Chimio® databases. Methods PRA has two main stages, PRA “system” and PRA “scenario”. A multidisciplinary working group is created for the entire PRA process. PRA “system” is an exploratory and qualitative stage. PRA “scenario” requires the creation of risk assessment tools and decision tools before actually developing, analysing and treating scenarios, with risk reduction actions structured in an action plan. For PRA2 we used the same working group, assessment and decision tools as for PRA1 and we only analysed dangerous situations (DS) that appeared or changed towards more risk, requiring a new action plan. The different PRA only required four 2 h meetings thanks to the investment of a coordinator who is expert in the method. Results In PRA1, the riskiest phase was production while it was the verification and delivery of the finished product in PRA2. The risks were mainly related to management, human and technical dangers in PRA1. Human danger was found to be the main danger in PRA2, followed by organisational danger. Among the 264 scenarios described in PRA1, six of criticality 3 and 69 of criticality 2 have been associated with risk reduction actions. These actions mainly involved managing the risk of human error, with the control system Drugcam® and the standardisation of the pharmaceutical assistants’ training program. In PRA2, 11 scenarios were analysed, including three of criticality 3 and 4 of criticality 2 for which risk reduction measures were taken. Conclusions PRA allowed us to perform an in depth analysis of the highly specific and technical process of anticancer drug preparation. Human danger was one of the most important dangers identified, and it should always be taken into consideration, whatever the measures taken to prevent it. PRA2 was extremely useful to plan the organisation that would result from the new Chimio® database, while involving the team and winning its commitment. It allowed an exhaustive and structured anticipation of this major change. Practical aspects of PRA method implementation we have adopted facilitate its application and can help to deploy it on many areas in our hospitals. Indeed, besides an exhaustive analysis of the risks, this approach promotes collaboration, develops a quality culture and is an excellent tool for team and project management, as well as communication.

High-flow nasal cannula (HFNC) oxygen therapy has recently shown clinical benefits in hypoxaemic acute respiratory failure (ARF) patients, while the value of noninvasive ventilation (NIV) remains debated. The primary end-point was to compare alveolar recruitment using global end-expiratory electrical lung impedance (EELI) between HFNC and NIV. Secondary end-points compared regional EELI, lung volumes (global and regional tidal volume variation (VT)), respiratory parameters, haemodynamic tolerance, dyspnoea and patient comfort between HFNC and NIV, relative to face mask (FM). A prospective randomised crossover physiological study was conducted in patients with hypoxaemic ARF due to pneumonia. They received alternately HFNC, NIV and FM. 16 patients were included. Global EELI was 4083 with NIV and 2921 with HFNC (p=0.4). Compared to FM, NIV and HFNC significantly increased global EELI by 1810.5 (95% CI 857–2646) and 826 (95% CI 399.5–2361), respectively. Global and regional VT increased significantly with NIV compared to HFNC or FM, but not between HFNC and FM. NIV yielded a significantly higher pulse oxygen saturation/inspired oxygen fraction ratio compared to HFNC (p=0.03). No significant difference was observed between HFNC, NIV and FM for dyspnoea. Patient comfort score with FM was not significantly different than with HFNC (p=0.1), but was lower with NIV (p=0.001). This study suggests a potential benefit of HFNC and NIV on alveolar recruitment in patients with hypoxaemic ARF. In contrast with HFNC, NIV increased lung volumes, which may contribute to overdistension and its potentially deleterious effect in these patients., This study found a potential benefit of HFNC and NIV on alveolar recruitment in patients with hypoxaemic ARF, but NIV also increases lung volumes, which may give rise to overdistension, reinforcing the concept of patient self-inflicted lung injury https://bit.ly/3iRcZDJ

We studied COVID-19 associated mucormycosis based on 17 cases reported nationwide and assessed the differences with India. They differed by frequencies of diabetes mellitus (47% in France versus up to 95% in India), hematological malignancies (35% versus 1%), anatomical sites (12% versus >80% rhino-orbito-cerebral) and prognosis (88% mortality versus, We reported 17 cases of COVID-19 associated mucormycosis in France. Compared to India, they differed by frequencies of diabetes mellitus (47% versus up to 95% in India), hematological malignancies (35% versus 1%), anatomical sites and mortality (88% versus

Background Early reports show the unequal effect the COVID-19 pandemic might have on men versus women engaged in medical research. Purpose To investigate whether the COVID-19 pandemic has had an impact on scientific publishing by female physicians in medical imaging. Materials and Methods The authors conducted a descriptive bibliometric analysis of the gender of the first and last authors of manuscripts submitted to the top 50 medical imaging journals from March to May 2020 (n = 2480) compared with the same period of the year in 2018 (n = 2238) and 2019 (n = 2355). Manuscript title, date of submission, first and last names of the first and last authors, journal impact factor, and author country of provenance were recorded. The Gender-API software was used to determine author gender. Statistical analysis comprised χ2 tests and multivariable logistic regression. Results Percentages of women listed as first and last authors were 31.6% (1172 of 3711 articles) and 19.3% (717 of 3711 articles), respectively, in 2018-2019 versus 32.3% (725 of 2248 articles) and 20.7% (465 of 2248 articles) in 2020 (P = .61 and P = .21, respectively). For COVID-19-related articles, 35.2% (89 of 253 articles) of first authors and 20.6% (52 of 253 articles) of last authors were women. No associations were found between first- and last-author gender, year of publication, and region of provenance. First and last authorship of high-ranking articles was not in favor of North American women whatever the year (odds ratio [OR], 0.79 [P = .05] and 0.72 [P = .02], respectively). Higher rates of female last authorship of high-ranking articles were observed in Europe (P = .003) and of female first authorship of low-ranking publications in Asia in 2020 (OR, 1.38; 95% CI: 0.98, 1.92; P = .06). Female first and last authorship of COVID-19-related articles was overrepresented for lowest-rank publications (P = .02 and P = .01, respectively). Conclusion One in three first authors and one in five last authors were women in 2018-2019 and 2020, respectively. Although the first 2020 lockdown did not diminish the quantity of women-authored publications, the impact on the quality was variable. ©RSNA, 2021 See also the editorial by Robbins and Khosa in this issue.

The specific concentrations of colistin in non-target feed for food-producing animals, below which there would not be an effect on the emergence of, and/or selection for, resistance in bacteria relevant for human and animal health, as well as the specific antimicrobial concentrations in feed which have an effect in terms of growth promotion/increased yield were assessed by EFSA in collaboration with EMA. Details of the methodology used for this assessment, associated data gaps and uncertainties, are presented in a separate document. To address antimicrobial resistance, the Feed Antimicrobial Resistance Selection Concentration (FARSC) model developed specifically for the assessment was applied. However, due to the lack of data on the parameters required to calculate the FARSC, it was not possible to conclude the assessment until further experimental data become available. To address growth promotion, data from scientific publications obtained from an extensive literature review were used. Levels of colistin in feed that showed to have an effect on growth promotion/increased yield were reported. It was recommended to carry out studies to generate the data that are required to fill the gaps which prevented the calculation of the FARSC for these antimicrobials. info:eu-repo/semantics/publishedVersion

The specific concentrations of trimethoprim in non-target feed for food-producing animals below which there would not be an effect on the emergence of, and/or selection for, resistance in bacteria relevant for human and animal health, as well as the specific antimicrobial concentrations in feed which have an effect in terms of growth promotion/increased yield were assessed by EFSA in collaboration with EMA. Details of the methodology used for this assessment, associated data gaps and uncertainties, are presented in a separate document. To address antimicrobial resistance, the Feed Antimicrobial Resistance Selection Concentration (FARSC) model developed specifically for the assessment was applied. The FARSC for trimethoprim was estimated. Uncertainties and data gaps associated to the levels reported were addressed. To address growth promotion, data from scientific publications obtained from an extensive literature review were used. No suitable data for the assessment were available. It was recommended to perform further studies to supply more diverse and complete data related to the requirements for calculation of the FARSC for trimethoprim. info:eu-repo/semantics/publishedVersion

The specific concentrations of tiamulin and valnemulin in non-target feed for food-producing animals, below which there would not be an effect on the emergence of, and/or selection for, resistance in bacteria relevant for human and animal health, as well as the specific antimicrobial concentrations in feed which have an effect in terms of growth promotion/increased yield were assessed by EFSA in collaboration with EMA. Details of the methodology used for this assessment, associated data gaps and uncertainties, are presented in a separate document. To address antimicrobial resistance, the Feed Antimicrobial Resistance Selection Concentration (FARSC) model developed specifically for the assessment was applied. However, due to the lack of data on the parameters required to calculate the FARSC, it was not possible to conclude the assessment until further experimental data become available. To address growth promotion, data from scientific publications obtained from an extensive literature review were used. Levels in feed that showed to have an effect on growth promotion/increased yield were reported for tiamulin, while for valnemulin no suitable data for the assessment were available. It was recommended to carry out studies to generate the data that are required to fill the gaps which prevented the calculation of the FARSC for these two antimicrobials. info:eu-repo/semantics/publishedVersion

Background Several randomized clinical trials have shown that non-invasive ventilation (NIV) applied immediately after extubation may prevent reintubation in patients at high-risk of extubation failure. However, most of studies included patients with chronic respiratory disorders as well as patients without underlying respiratory disease. To date, no study has shown decreased risk of reintubation with prophylactic NIV after extubation among patients with chronic obstructive pulmonary disease (COPD). We hypothesized that prophylactic NIV after extubation may decrease the risk of reintubation in COPD patients as compared with high-flow nasal oxygen. We performed a post hoc subgroup analysis of COPD patients included in a multicenter, randomized, controlled trial comparing prophylactic use of NIV alternating with high-flow nasal oxygen versus high-flow nasal oxygen alone immediately after extubation. Results Among the 651 patients included in the original study, 150 (23%) had underlying COPD including 86 patients treated with NIV alternating with high-flow nasal oxygen and 64 patients treated with high-flow nasal oxygen alone. The reintubation rate was 13% (11 out of 86 patients) with NIV and 27% (17 out of 64 patients) with high-flow nasal oxygen alone [difference, − 14% (95% CI − 27% to − 1%); p = 0.03]. Whereas reintubation rates were significantly lower with NIV than with high-flow nasal oxygen alone at 72 h and until ICU discharge, mortality in ICU did not differ between groups: 6% (5/86) with NIV vs. 9% (6/64) with high-flow nasal oxygen alone [difference − 4% (95% CI − 14% to 5%); p = 0.40]. Conclusions In COPD patients, prophylactic NIV alternating with high-flow nasal oxygen significantly decreased the risk of reintubation compared with high-flow nasal oxygen alone. Trial registration The study was registered at http://www.clinicaltrials.gov with the trial registration number NCT03121482 (20 April 2017)

Foreign Body Reaction (FBR) is a critical issue to be addressed when polyethylene terephthalate (PET) textile implants are considered in the medical field to treat pathologies involving hernia repair, revascularization strategies in arterial disease, and aneurysm or heart valve replacement. The natural porosity of textile materials tends to induce exaggerated tissue ingrowth which may prevent the implants from remaining flexible. The purpose of this study is to assess the influence of the textile topography of various woven substrates on the wetting properties of these substrates and on their in vitro interaction with mesenchymal stem cells (MSC) at 24 and 72 hr. The tests were performed both at yarn and fabric level under forced wetting and ingrowth conditions in order to replicate the mechanisms going on in vivo under blood pressure. Results demonstrate that cell proliferation is influenced by the textile wetting properties, which can be tuned at yarn and fabric level. In particular, it is shown that a satin weave obtained from porous spun yarn limits cell proliferation due to the high porosity of the yarn and the limited saturation index of the weave. Yarn and fabric saturation seems to play a predominant role in cell proliferation on textile substrates.

Identification of the acoustic environment from an audio recording, also known as acoustic scene classification, is an active area of research. In this paper, we study dynamically-changing background acoustic scenes from the egocentric perspective of an individual in a workplace. In a novel data collection setup, wearable sensors were deployed on individuals to collect audio signals within a built environment, while Bluetooth-based hubs continuously tracked the individual's location which represents the acoustic scene at a certain time. The data of this paper come from 170 hospital workers gathered continuously during work shifts for a 10 week period. In the first part of our study, we investigate temporal patterns in the egocentric sequence of acoustic scenes encountered by an employee, and the association of those patterns with factors such as job-role and daily routine of the individual. Motivated by evidence of multifaceted effects of ambient sounds on human psychology, we also analyze the association of the temporal dynamics of the perceived acoustic scenes with particular behavioral traits of the individual. Experiments reveal rich temporal patterns in the acoustic scenes experienced by the individuals during their work shifts, and a strong association of those patterns with various constructs related to job-roles and behavior of the employees. In the second part of our study, we employ deep learning models to predict the temporal sequence of acoustic scenes from the egocentric audio signal. We propose a two-stage framework where a recurrent neural network is trained on top of the latent acoustic representations learned by a segment-level neural network. The experimental results show the efficacy of the proposed system in predicting sequence of acoustic scenes, highlighting the existence of underlying temporal patterns in the acoustic scenes experienced in workplace.

BACKGROUND The objective of this study was to describe labor duration of women managed with current obstetric practices in a French national population-based cohort and to assess the association of age and BMI on this duration. METHODS All women in the French perinatal survey of 2016 with a singleton cephalic fetus, delivering at term after a spontaneous labor were included. Duration of labor was defined as time between admission to the labor ward and birth. Duration of total labor and first and second stage of labor were described. Then, duration of labor was estimated according to maternal age and BMI, using Kaplan-Meier's method and compared with the log-rank test after stratification on parity. Intrapartum cesarean birth was considered as a censoring event. Multivariable modeling was performed using Cox's proportional hazard's method. RESULTS Data of 3120 nulliparous and 4385 multiparous women were analyzed. Median labor duration was 6.1 hours ([5th; 95th percentile]) [1.4; 12.6] and 3.1 hours [0.3; 8.5] in nulliparous and multiparous women. Multivariable Cox analysis showed no independent association of maternal age and duration of labor. Nulliparous obese women had significantly lower odds of having a shorter labor than women with a BMI

Background/Aims: Abnormal psychological profiles are frequently found in patients with functional gastrointestinal disorders (FGIDs). The present study aimed to evaluate the psychological profiles of FGID patients with irritable bowel syndrome (IBS), and IBS phenotypes.Methods: In 608 FGID patients, including 235 with IBS, have filled a Rome III questionnaire and the French version of the Minnesota Multiphasic Personality Inventory 2. Data analysis was performed using univariate analysis and multivariate logistic regression.Results: This study shows that IBS patients have abnormal psychological profiles with more significant symptom exaggeration and decreased test defensiveness than non-IBS patients. They have a significantly higher score for all clinical scales. Logistic regression analysis showed in IBS patients a decrease of body mass index (P= 0.002), and test defensiveness score K (P= 0.001) and an increase of Hypochondriasis (P< 0.001) and Masculinity-Femininity scale (P= 0.018). By comparison with non-IBS patients, IBS-constipation, IBS-diarrhea, and mixed IBS patients have increased Hypochondriasis value and Depression score, mixed IBS patients have higher Psychasthenia score and higher Hypomania score. No item was significantly different in the IBS-unspecified group.Conclusions: This study shows that IBS patients have different psychological profiles than other FGID patients and that psychological characteristics are associated with IBS phenotypes except for patients with unsubtyped IBS.

International audience; Extracorporeal membrane oxygenation (ECMO) is recognized as organ support for potentially reversible acute respiratory distress syndrome (ARDS). However, limited resource during the outbreak and the coagulopathy associated with coronavirus disease 2019 (COVID-19) make the utilization of venovenous (VV) ECMO highly challenging. We herein report specific considerations for cannulation configurations and ECMO management during the pandemic. High blood flow and anticoagulation at higher levels than usual practice for VV ECMO may be required because of thrombotic hematologic profile of COVID-19. Among our first 24 cases (48.8 ± 8.9 years), 17 patients were weaned from ECMO after a mean duration of 19.0 ± 10.1 days and 16 of them have been discharged from ICU.

International audience; Rationale: Data from population-based cohorts suggest that symptom subtypes and obstructive sleep apnea (OSA)-specific hypoxic burden (HB) could help to better identify patients with OSA at high cardiovascular (CV) risk. Objectives: We aimed to evaluate whether those new markers are associated with the risk of major adverse CV events (MACE) in clinical setting. Methods: Data from the Pays de la Loire cohort were linked to health administrative data to identify the occurrence of MACE (a composite outcome including all-cause mortality, acute myocardial infarction, stroke, and unplanned coronary revascularization) in patients with newly diagnosed OSA and no overt CV disease. Latent class analysis was used to identify subtypes based on eight clinically relevant variables. HB was defined as the total area under the respiratory event-related desaturation curve. Cox proportional hazards models were used to evaluate the association of symptom subtypes and HB with MACE. Measurements and Main Results: Four symptom subtypes were identified (minimally symptomatic [22.0%], disturbed sleep [17.5%], excessively sleepy [49.8%], and moderately sleepy [10.6%]). After a median follow-up of 78 months (interquartile range, 52-109), 592 (11.05%) of 5,358 patients experienced MACE. In a fully adjusted model, HB and overall nocturnal hypoxemia assessed by sleep time with oxygen saturation,90% were the only predictors ofMACE (hazard ratio, 1.21; 95% confidence interval, 1.07-1.38; and hazard ratio, 1.34; 95% confidence interval, 1.16-1.55, respectively). The association appeared stronger toward younger patients and women. Conclusion: In clinical setting, patients with OSA who demonstrate elevated OSA-specific HB are at higher risk of a CV event and all-cause mortality. Symptom subtypes were not associated with MACE after adjustment for confounders.

A variety of neuropsychiatric complications has been described in association with Covid-19 infection. Large scale studies presenting a wider picture of these complications and their relative frequency are lacking. The objective of our study was to describe the spectrum of neurological and psychiatric complications in patients with Covid-19 seen in a multidisciplinary hospital center over six months. We conducted a retrospective, observational study on all patients showing neurological or psychiatric symptoms in the context of Covid-19 seen in the medical and university neuroscience department of Assistance Publique Hopitaux de Paris -Sorbonne University. We collected demographic data, comorbidities, symptoms and severity of Covid-19 infection, neurological and psychiatric symptoms, neurological and psychiatric examination data and, when available, results from CSF analysis, MRI, EEG and EMG. A total of 249 Covid-19 patients with a de novo neurological or psychiatric manifestation were included in the database and 245 were included in the final analyses. One-hundred fourteen patients (47%) were admitted to the intensive care unit and 10 (4%) died. The most frequent neuropsychiatric complications diagnosed were encephalopathy (43%), critical illness polyneuropathy and myopathy (26%), isolated psychiatric disturbance (18%), and cerebrovascular disorders (16%). No patients showed CSF evidence of SARS-CoV-2. Encephalopathy was associated with older age and higher risk of death. Critical illness neuromyopathy was associated with an extended stay in the intensive care unit. The majority of these neuropsychiatric complications could be imputed to critical illness, intensive care and systemic inflammation, which contrasts with the paucity of more direct SARS-CoV-2-related complications or post-infection disorders., Graphical Abstract Graphical Abstract

Background In intensive care units (ICUs), patients experiencing post-extubation respiratory failure have poor outcomes. The use of noninvasive ventilation (NIV) to treat post-extubation respiratory failure may increase the risk of death. This study aims at comparing mortality between patients treated with NIV alternating with high-flow nasal oxygen or high-flow nasal oxygen alone. Methods Post-hoc analysis of a multicenter, randomized, controlled trial focusing on patients who experienced post-extubation respiratory failure within the 7 days following extubation. Patients were classified in the NIV group or the high-flow nasal oxygen group according to oxygenation strategy used after the onset of post-extubation respiratory failure. Patients reintubated within the first hour after extubation and those promptly reintubated without prior treatment were excluded. The primary outcome was mortality at day 28 after the onset of post-extubation respiratory failure. Results Among 651 extubated patients, 158 (25%) experienced respiratory failure and 146 were included in the analysis. Mortality at day 28 was 18% (15/84) using NIV alternating with high-flow nasal oxygen and 29% (18/62) with high flow nasal oxygen alone (difference, − 11% [95% CI, − 25 to 2]; p = 0.12). Among the 46 patients with hypercapnia at the onset of respiratory failure, mortality at day 28 was 3% (1/33) with NIV and 31% (4/13) with high-flow nasal oxygen alone (difference, − 28% [95% CI, − 54 to − 6]; p = 0.006). The proportion of patients reintubated 48 h after the onset of post-extubation respiratory failure was 44% (37/84) with NIV and 52% (32/62) with high-flow nasal oxygen alone (p = 0.21). Conclusions In patients with post-extubation respiratory failure, NIV alternating with high-flow nasal oxygen might not increase the risk of death. Trial registration number The trial was registered at http://www.clinicaltrials.gov with the registration number NCT03121482 the 20th April 2017.

Background Critically ill patients with obesity may have an increased risk of difficult intubation and subsequent severe hypoxemia. We hypothesized that pre-oxygenation with noninvasive ventilation before intubation as compared with high-flow nasal cannula oxygen may decrease the risk of severe hypoxemia in patients with obesity. Methods Post hoc subgroup analysis of critically ill patients with obesity (body mass index ≥ 30 kg·m−2) from a multicenter randomized controlled trial comparing preoxygenation with noninvasive ventilation and high-flow nasal oxygen before intubation of patients with acute hypoxemic respiratory failure (PaO2/FiO2 Results Among the 313 patients included in the original trial, 91 (29%) had obesity with a mean body mass index of 35 ± 5 kg·m−2. Patients with obesity were more likely to experience an episode of severe hypoxemia during intubation procedure than patients without obesity: 34% (31/91) vs. 22% (49/222); difference, 12%; 95% CI 1 to 23%; P = 0.03. Among patients with obesity, 40 received preoxygenation with noninvasive ventilation and 51 with high-flow nasal oxygen. Severe hypoxemia occurred in 15 patients (37%) with noninvasive ventilation and 16 patients (31%) with high-flow nasal oxygen (difference, 6%; 95% CI − 13 to 25%; P = 0.54). The lowest pulse oximetry values during intubation procedure were 87% [interquartile range, 77–93] with noninvasive ventilation and 86% [78–92] with high-flow nasal oxygen (P = 0.98). After multivariable analysis, factors independently associated with severe hypoxemia in patients with obesity were intubation difficulty scale > 5 points and respiratory primary failure as reason for admission. Conclusions Patients with obesity and acute hypoxemic respiratory failure had an increased risk of severe hypoxemia during intubation procedure as compared to patients without obesity. However, preoxygenation with noninvasive ventilation may not reduce this risk compared with high-flow nasal oxygen. Trial registration Clinical trial number: NCT02668458 (http://www.clinicaltrials.gov)

RATIONALE Whereas non-invasive ventilation (NIV) may prevent reintubation in patients at high-risk of extubation failure in intensive care units (ICUs), this oxygenation strategy has not been specifically assessed in obese patients. OBJECTIVES We hypothesized that NIV may decrease the risk of reintubation in obese patients compared with high-flow nasal oxygen (HFNO). METHODS Post-hoc analysis of a multicenter, randomized, controlled trial (not pre-specified) comparing NIV alternating with HFNO versus HFNO alone after extubation, with the aim of assessing NIV effects according to patient body-mass index (BMI). MEASUREMENTS AND MAIN RESULTS Among 623 patients at high-risk of extubation failure, 206 (33%) were obese (BMI≥30 kg/m2), 204 (33%) were overweight (25≤BMI

BackgroundDespite the PD-(L)1 therapy success, a majority of patients remain resistant. PD-1+IL7R+ progenitors CD8 TILs is a key T-cell subset associated with durable PD-(L)1 therapy response. However, this subset may rapidly undergo apoptosis and/or being fully exhausted after PD-(L)1 blockade. Some cytokines have the potential to strengthen PD-(L)1 therapy by promoting T cell survival, however, their clinical developments are limited by a shortened half-life and systemic toxicity. To redirect immunotherapy to tumor-specific T cells, expressing PD1, we propose to selectively deliver the pro-survival IL-7 to PD-1+ T cells using a bifunctional anti-PD1/IL-7 mutein antibody. We previously described that the anti-PD1/IL-7v abrogated suppressive activity of human Treg. Here we evaluated its preclinical anti-tumor efficacy and how it promotes the response of PD1+IL7R+ tumor-specific T cells.MethodsProliferation, IFN-γ, IL-7R signaling, and NFAT assays were tested to determine the mechanism of this antibody. For the suppressive assay, CD4 Treg and autologous CD8 Teff were co-cultured. In vivo experiments were performed in hPD-1 KI immunocompetent or humanized immunodeficient mice.ResultsThe anti-PD1/IL-7v antibody design has been optimized with a monovalent approach to enhance its biological activity: (1) preserved PD-1 antagonist activity, (2) improved pSTAT5 IL7R signaling, and (3) enhanced in vivo drug exposure and antitumor efficacy. An IL7 mutein has been designed to improve activity on PD1+ T cells while sparing PD1neg T cells.Using a chronic antigen stimulation model, anti-PD1/IL-7v restores the proliferation & survival of both early and fully exhausted CD8+ or CD4+ T cells. Similarly, anti-PD1/IL-7v, but not anti-PD1 alone, reactivates exhausted TILs isolated from human resected tumors. Gene expression analysis by Nanostring showed increase cytotoxicity, antigen presentation, and chemokines signatures. In vivo, anti-PD1/IL-7v demonstrated high monotherapy efficacy (90%) in a PD-1 sensitive orthotopic immunocompetent mouse tumor model as well as in a PD-1 refractory tumor model with 70% of CR vs 15% for anti-PD-1 alone. A selective higher expansion of stem-like/progenitors CD8 TILs was observed after therapy with anti-PD1/IL-7v compared to anti-PD1. Memory immune response was demonstrated in 100% of cured mice after tumor rechallenge in the absence of new treatment in 3 different tumor models. Finally, using two different humanized mouse models implanted with human tumors (A549 or MDA-MB231), we confirmed significant preclinical monotherapy efficacy of the anti-PD-1/IL7v.ConclusionsThese data highlight the potential of anti-PD1/IL-7 bifunctional drug to overcome immunotherapy resistance and to promote durable anti-tumor efficacy by preferentially reinvigorating PD-1+IL7R+ stem-like progenitors CD8 T cells.

International audience; Objective. Cardiovascular disease (CVD) is one of the leading causes of death worldwide. There are many CVD risk estimators but very few take into account sleep features. Moreover, they are rarely tested on patients investigated for obstructive sleep apnea (OSA). However, numerous studies have demonstrated that OSA index or sleep features are associated with CVD and mortality. The aim of this study is to propose a new simple CVD and mortality risk estimator for use in routine sleep testing.Approach. Data from a large multicenter cohort of CVD-free patients investigated for OSA were linked to the French Health System to identify new-onset CVD. Clinical features were collected and sleep features were extracted from sleep recordings. A machine-learning model based on trees, AdaBoost, was applied to estimate the CVD and mortality risk score.Main results. After a median [inter-quartile range] follow-up of 6.0 [3.5-8.5] years, 685 of 5234 patients had received a diagnosis of CVD or had died. Following a selection of features, from the original 30 features, 9 were selected, including five clinical and four sleep oximetry features. The final model included age, gender, hypertension, diabetes, systolic blood pressure, oxygen saturation and pulse rate variability (PRV) features. An area under the receiver operating characteristic curve (AUC) of 0.78 was reached.Significance. AdaBoost, an interpretable machine-learning model, was applied to predict 6 year CVD and mortality in patients investigated for clinical suspicion of OSA. A mixed set of simple clinical features, nocturnal hypoxemia and PRV features derived from single channel pulse oximetry were used.

Background Faced with an abrupt surge of severe COVID patients in March and April 2020, intensive care units (ICU) from four French regions transferred around 660 patients towards six other regions and four neighbouring countries. The intensity and the diversity of the vectors used (plane, helicopter, train, ambulance), during this wave of medical evacuations make it an unprecedented event. The aim of TRANSCOV is to examine the impact of long distance transfers on patient's health and to understand how actors collaborated to overcome clinical and logistical challenges. Methods TRANSCOV is made of three disciplinary components: 1) interviews with clinicians and health authorities staff involved in the organisation and realisation of the transfers as part of the qualitative component; 2) a retrospective cohort collecting clinical parameters and pathway details before during and after transfer; 3) a collection of data regarding human and logistical resources mobilised during transfers as part of an economical evaluation. Results Preliminary results indicate that prior experience in medical evacuations proved useful to collaborate effectively in the exceptional circumstances prevailing in spring 2020. Clinicians had to establish quickly eligibility criteria for transfer. Actors' opinions may vary on the appropriateness of vectors to transfer isolated (e.g. via helicopter) or grouped (train) patients. Early epidemiological data suggest that transferred patients were younger and experienced comparable, if not lower, in-hospital mortality compared to other patients. The economic evaluation is in progress. Conclusions Initial results indicate that effective collaborations led to the selection of clinically eligible patients and the realisation of safe distant transfers. Key messages Healthcare organisations have been able to adapt and create organizational innovations to respond to COVID-19. Multidisciplinary approaches are appropriate to evaluate such complex innovations.

The infant brain undergoes a remarkable period of neural development that is crucial for the development of cognitive and behavioral capacities (Hasegawa et al., 2018). Longitudinal magnetic resonance imaging (MRI) is able to characterize the developmental trajectories and is critical in neuroimaging studies of early brain development. However, missing data at different time points is an unavoidable occurrence in longitudinal studies owing to participant attrition and scan failure. Compared to dropping incomplete data, data imputation is considered a better solution to address such missing data in order to preserve all available samples. In this paper, we adapt generative adversarial networks (GAN) to a new application: longitudinal image prediction of structural MRI in the first year of life. In contrast to existing medical image-to-image translation applications of GANs, where inputs and outputs share a very close anatomical structure, our task is more challenging as brain size, shape and tissue contrast vary significantly between the input data and the predicted data. Several improvements over existing GAN approaches are proposed to address these challenges in our task. To enhance the realism, crispness, and accuracy of the predicted images, we incorporate both a traditional voxel-wise reconstruction loss as well as a perceptual loss term into the adversarial learning scheme. As the differing contrast changes in T1w and T2w MR images in the first year of life, we incorporate multi-contrast images leading to our proposed 3D multi-contrast perceptual adversarial network (MPGAN). Extensive evaluations are performed to assess the qualityand fidelity of the predicted images, including qualitative and quantitative assessments of the image appearance, as well as quantitative assessment on two segmentation tasks. Our experimental results show that our MPGAN is an effective solution for longitudinal MR image data imputation in the infant brain. We further apply our predicted/imputed images to two practical tasks, a regression task and a classification task, in order to highlight the enhanced task-related performance following image imputation. The results show that the model performance in both tasks is improved by including the additional imputed data, demonstrating the usability of the predicted images generated from our approach.

Severity of hypoxaemia can be assessed using the partial pressure of arterial oxygen to fraction of inspired oxygen ratio (FiO2). However, in patients breathing through non-rebreather reservoir bag oxygen mask, accuracy of bedside FiO2 estimation methods remains to be tested. In a post-hoc analysis of a multicentre clinical trial, three FiO2 estimation methods were compared with FiO2 measured with a portable oxygen analyser introduced in the oxygen mask. Among 262 patients analysed, mean (SD) measured FiO2 was 65% (13). The 3%-formula (21% + oxygen flow rate in L/min × 3) was the most accurate method to estimate FiO2. Other methods overestimated FiO2 and hypoxaemia severity, so they should be avoided.

Aims Intravenous mycophenolate mofetil (IV MMF), a prodrug of mycophenolic acid (MPA), is used during nonmyeloablative and reduced-intensity conditioning haematopoetic stem cell transplantation (HCT) to improve engraftment and reduce graft-versus-host disease. The aims of this study were to develop population pharmacokinetic models and Bayesian estimators based on limited sampling strategies to allow for individual dose adjustment of intravenous mycophenolate mofetil administered by infusion in haematopoietic stem cell transplant patients. Methods Sixty-three MPA concentration-time profiles (median [min-max] = 6 [4-7] samples) were collected from 34 HCT recipients transplanted for 14 (1-45) days and administered IV MMF every 8 hours, concomitantly with cyclosporine. The database was split into development (75%) and validation (25%) datasets. Pharmacokinetic models characterized by a single compartment with first-order elimination, combined with two gamma distributions to describe the transformation of MMF into mycophenolic acid, were developed using in parallel nonparametric (Pmetrics) and parametric (ITSIM) approaches. The performances of the models and the derived Bayesian estimators were evaluated in the validation set. Results The best limited sampling strategy led to a bias (min, max), root mean square error between observed and modeled interdose areas under the curve in the validation dataset of -11.72% (-31.08%, 5.00%), 14.9% for ITSIM and -2.21% (-23.40%, 30.01%), 12.4% for Pmetrics with three samples collected at 0.33, 2 and 3 hours post dosing. Conclusion Population pharmacokinetic models and Bayesian estimators for IV MMF in HCT have been developed and are now available online (https://pharmaco.chu-limoges.fr) for individual dose adjustment based on the interdose area under the curve.

OBJECTIVES In lung transplantation (LT), femoral venoarterial extracorporeal membrane oxygenation (VA-ECMO) usually requires an open approach that may be associated with severe groin wound infection. In endovascular aortic procedures, preclosing of the femoral artery (PFA) with vascular closure devices allows the percutaneous insertion and withdrawal of large-bore cannulae. We sought to evaluate whether this innovative technique could be applied in the specific setting of LT to achieve total percutaneous VA-ECMO and decrease groin wound infection. METHODS We conducted a retrospective study of a prospective database including patients who underwent LT in our centre from January 2011 to December 2017. Patients who underwent peripheral VA-ECMO using the PFA technique after January 2014 (PFA group, n = 106) were compared to those who underwent peripheral VA-ECMO using open cannulation and/or decannulation before January 2014 (non-PFA group, n = 48). The primary end point was the rate of technical success defined as total percutaneous VA-ECMO. Secondary end points included groin wound infections and delayed vascular complications. RESULTS The PFA technique was technically successful in 98 patients (92.5%). As compared with the non-PFA group, the PFA group was characterized by a similar rate of vascular complications (16.6% vs 11.3%, P = 0.360) and a decreased rate of groin wound infection (18.9% vs 0%, P CONCLUSIONS In LT patients, PFA is associated with a high rate of total percutaneous VA-ECMO, thus preventing the occurrence of groin wound infection.

Rapid assessment of hemostasis during postpartum hemorrhage (PPH) is essential to allow characterization of coagulopathy, to estimate bleeding severity, and to improve outcome. Point of care (POC) coagulation monitors could be of great interest for early diagnosis and treatment of coagulation disorders in PPH.Women with ongoing PPH500 mL who clinically required an assessment of coagulation with thromboelastography (TEG) were included. The primary aim of this retrospective observational cohort study was to assess the predictive accuracy of TEG parameters for the diagnosis of coagulation disorders (hypofibrinogenemia ≤2 g/L, thrombocytopenia ≤80,000/mm, prothrombin ratio ≤50%, or activated partial thromboplastin time ratio ≥1.5) during PPH. The analyzed TEG parameters were Kaolin-maximum amplitude (K-MA), Kaolin-maximum rate of thrombus generation using G (K-MRTGG), functional fibrinogen-maximum amplitude (FF-MA), and functional fibrinogen-maximum rate of thrombus generation using G (FF-MRTGG). Secondary aims of this study were (1) comparison of the time delay between classical parameters and velocity curve-derived parameters (K-MA versus K-MRTGG and FF-MA versus FF-MRTGG) and (2) evaluation of the accuracy of TEG parameters to predict severe hemorrhage estimated by calculated blood losses.Ninety-eight patients were included with 98 simultaneous TEG analyses and laboratory assays. All parameters had an excellent predictive performance. For the Kaolin assay, no significant difference was evidenced between K-MA and K-MRTGG for the predictive performance for hypofibrinogenemia ≤2 g/L and/or thrombocytopenia ≤80,000/mm (respective area under the curve [AUC], 0.970 vs 0.981). For the functional fibrinogen assay, no significant difference was evidenced between FF-MA and FF-MRTGG for the predictive performance for hypofibrinogenemia ≤2 g/L (respective AUC, 0.988 vs 0.974). For both assays, the time to obtain results was shorter for the velocity parameters (K-MRTGG: 7.7 minutes [2.4 minutes] versus K-MA: 24.7 minutes [4.2 minutes], P.001; FF-MRTGG: 2.7 minutes [2.7 minutes] versus FF-MA: 14.0 minutes [4.3 minutes], P.001). All TEG parameters derived from the Kaolin and functional fibrinogen assays and Clauss fibrinogen were significantly predictive of severe PPH2500 mL.During PPH, when coagulation assessment is indicated, TEG provides a rapid and reliable detection of hypofibrinogenemia ≤2 g/L and/or thrombocytopenia ≤80,000/mm. No difference in performance was evidenced between the velocity-derived parameters (K-MRTGG and FF-MRTGG) and the classical parameters (K-MA and FF-MA). However, velocity-derived parameters offer the advantage of a shorter time to obtain results: FF-MRTGG parameter is available within ≤5 minutes. POC assessment of hemostasis during PPH management may help physicians to diagnose clotting disorders and to provide appropriate hemostatic support.

BackgroundYounger siblings of children with autism spectrum disorder (ASD) are at increased likelihood of receiving an ASD diagnosis and exhibiting other developmental concerns. It is unknown how quantitative variation in ASD traits and broader developmental domains in older siblings with ASD (probands) may inform outcomes in their younger siblings.MethodsParticipants included 385 pairs of toddler siblings and probands from the Infant Brain Imaging Study. ASD probands (mean age 5.5 years, range 1.7 to 15.5 years) were phenotyped using the Autism Diagnostic Interview-Revised (ADI-R), the Social Communication Questionnaire (SCQ), and the Vineland Adaptive Behavior Scales, Second Edition (VABS-II). Siblings were assessed using the ADI-R, VABS-II, Mullen Scales of Early Learning (MSEL), and Autism Diagnostic Observation Schedule (ADOS) and received a clinical best estimate diagnosis at 24 months using DSM-IV-TR criteria (n = 89 concordant for ASD;n = 296 discordant). We addressed two aims: (1) to determine whether proband characteristics are predictive of recurrence in siblings and (2) to assess associations between proband traits and sibling dimensional outcomes at 24 months.ResultsRegarding recurrence risk, proband SCQ scores were found to significantly predict sibling 24-month diagnostic outcome (OR for a 1-point increase in SCQ = 1.06; 95% CI = 1.01, 1.12). Regarding quantitative trait associations, we found no significant correlations in ASD traits among proband-sibling pairs. However, quantitative variation in proband adaptive behavior, communication, and expressive and receptive language was significantly associated with sibling outcomes in the same domains; proband scores explained 9–18% of the variation in cognition and behavior in siblings with ASD. Receptive language was particularly strongly associated in concordant pairs (ICC = 0.50,p ConclusionsProband ASD symptomology, indexed by the SCQ, is a predictor of familial ASD recurrence risk. While quantitative variation in social communication and restricted and repetitive behavior were not associated among sibling pairs, standardized ratings of proband language and communication explained significant variation in the same domains in the sibling at 24 months, especially among toddlers with an ASD diagnosis. These data suggest that proband characteristics can alert clinicians to areas of developmental concern for young children with familial risk for ASD.

Objective To evaluate whether the decrease in the frequency of oxytocin administration and artificial rupture of membranes observed between the 2010 and 2016 French Perinatal Surveys was associated with a change in the frequency of cesarean delivery or cesarean delivery indications among women who entered labor spontaneously. Methods This cross-sectional study included women who participated in the 2010 and 2016 French National surveys who had singleton pregnancies and who gave birth at at least 37 weeks of gestation after spontaneous labor to a liveborn neonate in cephalic presentation. To test whether the observed decrease of oxytocin administration and artificial rupture of membranes between the two study years was explained by the women's individual characteristics and maternity units' organizational characteristics change, multivariable analyses were performed. The same strategy was applied for the change in intrapartum cesarean delivery rates between the 2 years. These analyses were repeated in nulliparous, low obstetric risk women, multiparous low obstetric risk women, and women with a previous cesarean delivery. The cesarean delivery indications were compared in 2010 and 2016. Results Oxytocin administration decreased significantly from 58.3% in 2010 to 45.2% in 2016 (adjusted odds ratio [aOR] 0.51; 95% CI 0.47-0.55), as did artificial rupture of membranes, from 52.4% to 42.6% (aOR 0.66; 95% CI 0.62-0.71). The intrapartum cesarean delivery rate remained stable-6.9% compared with 6.6% (aOR 0.93; 95% CI 0.82-1.06). The same patterns were observed in low risk groups and women with a previous cesarean delivery. The cesarean delivery indications were similar in both years. Conclusion The significant decrease in oxytocin administration and artificial rupture of membranes in 2016 compared with 2010 was not accompanied by an increase in the intrapartum cesarean delivery rate for women in France who entered labor spontaneously. These results support the recent international guidelines.

Resume Objectif Determiner la prise en charge des patientes avec une rupture des membranes a terme avant travail (RMTAT). Methodes Synthese de la litterature a partir des bases de donnees PubMed et Cochrane et des recommandations des societes et colleges francais et etrangers. Resultats Une RMTAT est definie par une rupture des membranes apres 37 semaines d’amenorrhee (SA) en l’absence de travail (Accord professionnel). La RMTAT est consideree comme un processus physiologique jusqu’a 12 heures de rupture (Accord professionnel). En cas d’attitude expectative, avec un faible taux d’antibioprophylaxie, la prise en charge a domicile en comparaison a l’hospitalisation pourrait etre associee a une augmentation du taux d’infections neonatales (NP3) et ce d’autant qu’il existe une colonisation au streptocoque du groupe B (NP3). La prise en charge a domicile n’est donc pas recommandee (Grade C). Lors d’une RMTAT, en l’absence de travail spontane dans les 12 heures suivant la rupture, une antibioprophylaxie pourrait diminuer le taux d’infection intra-uterine (IIU) sans diminuer le taux d’infection neonatale bacterienne precoce (INBP) (NP3). Son utilisation dans les RMTAT, apres 12 h de RMTAT est donc recommandee (Grade C). Lorsqu’une antibioprophylaxie est indiquee, une betalactamine par voie intraveineuse sera privilegiee (Grade C). Le declenchement du travail par oxytocine (NP2), prostaglandines E2 (NP2), ou misoprostol (NP2) permet de raccourcir le delai entre la rupture des membranes et l’accouchement en comparaison a l’expectative. Un declenchement immediat du travail n’est pas associe a une reduction de l’INBP en comparaison a une attitude expectative (NP1), et ce quel que soit le statut des patientes pour le streptocoque B (NP2). Le declenchement n’est pas associe a une augmentation ou une reduction du taux de cesarienne en comparaison a une attitude expectative (NP2), quels que soient la parite (NP2) et le score de Bishop (NP3). En cas de RMTAT, l’attitude expectative peut etre proposee sans augmenter le risque infectieux neonatal (Grade B), et ce meme en cas de depistage positif pour le streptocoque B (Accord professionnel) et un declenchement peut etre propose sans augmenter le risque de cesarienne (Grade B). Les differentes methodes de declenchement (oxytocine, dinoprostone, misoprostol, sonde de Foley®) n’ont pas permis de demontrer la superiorite d’une strategie par rapport a une autre, que ce soit pour diminuer le taux d’IIU ou d’INBP, le taux de cesarienne ou raccourcir le delai declenchement-accouchement ; et ce quel que soit le score de Bishop ou la parite. Conclusion La RMTAT est un evenement frequent. Un delai de 12 heures, apres la rupture, sans entree en travail spontane, a ete retenu pour differencier une situation physiologique d’une situation potentiellement a risque pouvant justifier une antibioprophylaxie. En cas de RMTAT, l’attitude expectative ou le declenchement du travail peuvent etre proposes et ce, meme en cas de depistage positif pour le streptocoque B, en fonction du desir de la patiente et de l’organisation des soins dans les maternites (Accord professionnel).

Low-grade heat (below 200 °C) is available in vast quantities from industry, or from standard roof-top solar thermal collectors. However, the production of electric power from these heat sources is challenging with existing technologies. Thermally regenerative batteries allow both the conversion and the storage of thermal energy into electric power, but they suffer from low operation voltages and low output power. Here, we propose a thermally regenerative nanoslurry flow battery based on copper complexation with acetonitrile in non-aqueous solutions operating at voltages above 1 V. The Cu(i) complex can be destabilized by the removal of acetonitrile by distillation, leading to the production of solid copper nanoparticles and Cu(ii) in solution, thereby charging the battery. We demonstrate the electricity production at average power densities of 90 W m-2 and peak-power densities up to 150 W m-2, and estimate the theoretical efficiency of the full system at 2%. The results demonstrate a proof-of-concept for harvesting and storage of electricity from low-quality heat.

Psychological factors are involved in many functional gastrointestinal disorders including globus. The aim of the present study was to assess the clinical and psychological correlates associated with globus.707 patients (69% female, 45.2 ± 16.5 years, BMI 27.2 ± 11.7 kg/m140 patients (20%) reported suffering from globus. Globus appeared to be associated with older age (P = 0.001; OR = 1.022; 95% CI = [1.009-1.035]), increased BMI (P = 0.007; OR = 1.029; 95% CI = [1.008-1.051]), higher prevalence of regurgitations (P = 0.008; OR = 2.189; 95% CI = [1.228-3.902]), heartburn (P = 0.001 OR = 2.227; 95% CI = [1.406-3.530]), dysphagia (P 0.001; OR = 2.399; 95% CI = [1.500-3.837]), epigastric pain (P 0.001; OR = 3.768; 95% CI = [1.880-7.552]) and nonspecific dyspepsia (P = 0.018; OR = 1.786; 95% CI = [1.106-2.881]), and a higher score of hysteria (P = 0.008 OR = 1.034; 95% CI = [1.009-1.059]). By comparison with patients who reported globus and scores of hysteria in the normal range (n = 73), patients complaining of globus associated with high scores of hysteria (n = 67) have high scores of hypochondriasis (P 0.001; OR = 1.235; 95% CI = [1.142-1.336]), high levels of Psychopathic deviate (P = 0.005; OR = 1.091; 95% CI = [1.026-1.161]) and a higher, but not significant, prevalence of complaints of regurgitation (P = 0.052; OR = 4.022; 95% CI = [0.989-16.351]).Approximately 50% of the patients complaining of globus have a high score of hysteria associated with other personality disorders, and complain more frequently of regurgitation than other patients complaining of globus. These results tend to confirm that globus has a strong, although not systematic, connections with some specific personality disorders.

Background The physical and mental health benefits of physical activity (PA) in older adults have been well-documented. However, a large proportion of older adults worldwide fail to meet the internationally recommended guidelines of 150 minutes of moderate intensity PA per week. Factors associated with engagement in PA among older adults are complex, interacting and wide-reaching, involving individual, social, physical and environmental factors. Thus, to develop preventive lifestyle interventions it is necessary to carefully explore these factors. Methods This qualitative study (as part of a larger funded study to develop a PA-intervention) sought to identify and explore facilitators and barriers to PA in community dwelling older adults (≥65). Focus groups were conducted in Ireland (one) and France (two) and findings were analysed using thematic analysis. Results The main facilitators that emerged from focus group participants (n=33) were: availability of resources; tailored classes facilitated by staff knowledgeable of older adults’ needs; activities that facilitated social support and connectedness; perceived physical and psychological health benefits. Similar factors also influence continued participation in PA, as well as feelings of wellbeing and enjoyment, family support and motivation, although it was noted that it did sometimes require considerable effort. Barriers to engagement in PA included: lack of social support and resources; environmental factors, whether built, social, location or weather-related. Barriers of a more personal nature also emerged and included fear, loss of confidence due to functional changes, and lack of opportunity. Conclusion PA guidelines are but the first step. There is a need to develop implementation strategies at all levels: personal; interpersonal; organisational; community; and public policy, specifically for older adults, that will incorporate the above facilitators and address the above barriers to optimize engagement and maintenance in PA among older adults.

Background Upper-limb injuries and musculoskeletal disorders represent a major economic burden for both patients and society, largely due to limitations in returning to work. We hypothesized that a positive patient-surgeon relationship may facilitate patients' recovery and lead to a faster return to work. Methods This longitudinal observational study comprised 219 patients, from 8 French hand trauma centers, who were 18 to 55 years of age and were on sick leave from work because of an injury or musculoskeletal disorder of the upper limb. In addition to instruments measuring patients' functional scores and quality of life, the quality of the patient-surgeon relationship was assessed at enrollment using a specific questionnaire (Q-PASREL [Quality of PAtient-Surgeon RELationship]). Six months after enrollment, the return-to-work status was assessed. Logistic and Cox regression models were developed to identify predictors of return to work (yes/no) and the time off from work in days. Results Overall, 74% of the patients who returned to work within 6 months after enrollment had a high or medium-high Q-PASREL score, whereas 64% of the patients who were still on sick leave had a low or medium-low Q-PASREL score. The odds of patients with a low or medium-low Q-PASREL score returning to work were, respectively, 95% and 71% lower than the odds of patients with a high score doing so, with a percent difference of 56% (95% confidence interval [CI] = 40% to 71%) for low versus high (odds ratio [OR] = 0.05 [95% CI = 0.02 to 0.13]) and 25% (95% CI = 6% to 44%) for medium-low versus high (OR = 0.29 [95% CI = 0.11 to 0.76]). All Q-PASREL items and scores were significantly associated with return to work. Conclusions Patients with a lower Q-PASREL score and more severe disability were less likely to return to work within 6 months and had a longer time off from work. Efforts to improve the quality of patient-surgeon relationships may minimize the duration of sick leaves and accelerate patient recovery. Level of evidence Prognostic Level II. See Instructions for Authors for a complete description of levels of evidence.

Unfractionated heparin (UFH) is the main anticoagulant used in intensive care unit. The anticoagulant effect is monitored by activated partial thrombin time (aPTT) and anti-Xa activity (anti-Xa) measurement. However, delayed centrifugation induces platelet factor 4 (PF4) release and anti-Xa decrease. Several studies have concluded that aPTT and anti-Xa measurement should be performed within 2 h in citrated anticoagulant but may be delayed longer in Citrate Theophylline Adenosine and Dypiridamol (CTAD) anticoagulant. The objective of this study was to compare the stability of both aPTT and anti-Xa in citrate and CTAD samples, and to determine the effect of delayed centrifugation on both aPTT, anti-Xa results, and PF4 release in citrate samples only. aPTT and anti-Xa were measured in citrate and CTAD anticoagulant samples from 93 patients. Delayed centrifugation was performed in citrate samples from 31 additional patients, with hourly aPTT and anti-Xa measurement from 1 to 6 h. In 14 of these last patients, PF4 release was also evaluated with Human CXCL4/PF4 Quantikine ELISA Kit. We observed a significant correlation between citrate and CTAD anticoagulant for aPTT (r2 = 0.94) and anti-Xa (r2 = 0.95). With Bland–Altman correlation, a minor bias was observed for anti-Xa (− 0.025 ± 0.041). Delayed centrifugation in citrated anticoagulant showed an excellent concordance from 1 to 4 h for aPTT (− 4.0 ± 5.3 s) and anti-Xa (1.10−9 ± 0.058 UI/ml) measurements. Moreover, PF4 release was not different between 1 h (31.5 ± 14.7 ng/ml) and 4 h (33.8 ± 11.8 ng/ml). We have demonstrated that anti-Xa measurement for unfractionated heparin should be done 4 h in citrated plasma and that CTAD was not better than citrate. However, these initial findings require confirmation using other aPTT and calibrated anti-Xa assays.

Introduction In case of term prelabor rupture of membranes (PROM), expectant management is a reasonable option. We aimed at assessing the frequency of spontaneous onset of labor after two days of term PROM and its associated factors. Material and Methods Women delivering at a tertiary center of a singleton in cephalic presentation, after a term PROM with an unfavorable cervix and with an expectant management period of at least two days were included during a 2-year period. Women were excluded in case of induction of labor before or at day 2(D2) or of spontaneous labor before D2. The frequency of spontaneous labor was assessed, then maternal characteristics at admission and at D2 were compared between women with a spontaneous onset of labor before D3, and women with an induced labor at D3. The maternal and neonatal outcomes were compared between the two groups. The factors associated with spontaneous labor in univariate analysis were tested in multivariable analysis. Results Among the 11 608 women delivering at term, 933(8.4%) had a term PROM. Among them, 191 had an unfavorable cervix after D2 including 86(45%) women with a spontaneous labor onset between D2 and D3 and 105(55%) induced at D3. Maternal age below 35 years (reference ≥35years) and Bishop score of 3,4 and 5,6 at D2 (reference score 0–2) were significantly associated with spontaneous onset of labor, respectively aOR 2.62; 95%CI[1.26–5.45], aOR 2.38; 95%CI[1.18–4.78] and aOR 10.16; 95%CI[3.67–28.15]. Discussion In women with a term PROM and an unfavorable cervix, spontaneous labor still occurs in nearly half of women undelivered after two days of expectant management.

Apelin, a (neuro)vasoactive peptide, plays a prominent role in controlling body fluid homeostasis and cardiovascular functions. Experimental data performed in rodents have shown that apelin has an aquaretic effect via its central and renal actions. In the brain, apelin inhibits the phasic electrical activity of vasopressinergic neurons and the release of vasopressin from the posterior pituitary into the bloodstream and in the kidney, apelin regulates renal microcirculation and counteracts in the collecting duct, the antidiuretic effect of vasopressin occurring via the vasopressin receptor type 2. In humans and rodents, if plasma osmolality is increased by hypertonic saline infusion/water deprivation or decreased by water loading, plasma vasopressin and apelin are conversely regulated to maintain body fluid homeostasis. In patients with the syndrome of inappropriate antidiuresis, in which vasopressin hypersecretion leads to hyponatremia, the balance between apelin and vasopressin is significantly altered. In order to re-establish the correct balance, a metabolically stable apelin-17 analog, LIT01-196, was developed, to overcome the problem of the very short half-life (in the minute range) of apelin in vivo. In a rat experimental model of vasopressin-induced hyponatremia, subcutaneously (s.c.) administered LIT01-196 blocks the antidiuretic effect of vasopressin and the vasopressin-induced increase in urinary osmolality, and induces a progressive improvement in hyponatremia, suggesting that apelin receptor activation constitutes an original approach for hyponatremia treatment.

Purpose To report a French experience in patients admitted to Intensive Care Unit (ICU) for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) requiring high fractional concentration of inspired oxygen supported by high flow nasal cannula (HFNC) as first-line therapy. Methods Retrospective cohort study conducted in two ICUs of a French university hospital. All consecutive patients admitted during 28-days after the first admission for SARS-CoV-2 pneumonia were screened. Demographic, clinical, respiratory support, specific therapeutics, ICU length-of-stay and survival data were collected. Results Data of 43 patients were analyzed: mainly men (72%), median age 61 (51–69) years, median body mass index of 28 (25–31) kg/m2, median simplified acute physiology score (SAPS II) of 29 (22–37) and median PaO2/fraction of inspired oxygen (FiO2) (P/F) ratio of 146 (100–189) mmHg. HFNC was initiated at ICU admission in 76% of patients. Median flow was 50 (45–50) L/min and median FiO2 was 0.6 (0.5–0.8). 79% of patients presented at least one comorbidity, mainly hypertension (58%). At day (D) 28, 32% of patients required invasive mechanical ventilation, 3 patients died in ICU. Risk factors for intubation were diabetes (10% vs. 43%, P = 0.04) and extensive lesions on chest computed tomography (CT) (P = 0.023). Patients with more than 25% of lesions on chest CT were more frequently intubated during ICU stay (P = 0.012). At ICU admission (D1), patients with higher SAPS II and Sequential Organ Failure Assessment (SOFA) scores (respectively 39 (28–50) vs. 27 (22–31), P = 0.0031 and 5 (2–8) vs. 2 (2–2.2), P = 0.0019), and a lower P/F ratio (98 (63–109) vs. 178 (126–206), P = 0.0005) were more frequently intubated. Among non-intubated patients, the median lowest P/F was 131 (85–180) mmHg. Four caregivers had to stop working following coronavirus 2 contamination, but did not require hospitalization. Conclusion Our clinical experience supports the use of HFNC as first line-therapy in patients with SARS-COV-2 pneumonia for whom face mask oxygen does not provide adequate respiratory support.

International audience; Rationale: Nocturnal hypoxemia and sympathetic/parasympathetic imbalance might contribute to the occurrence or atrial fibrillation (AF) in patients with obstructive sleep apnea (OSA). During sleep recordings, pulse rate variability (PRV) derived from oximetry might provide an accurate estimation of heart rate variability, which reflects the autonomic cardiovascular control. Objectives: We aimed to evaluate whether indices of oxygen desaturation and PRV derived from nocturnal oximetry were associated with AF incidence in patients investigated for OSA. Methods: Data from a large multicenter cohort of AF-free patients investigated for OSA between May 15, 2007, and December 31, 2017, were linked to health administrative data to identify hospitalized and nonhospitalized patients with new-onset AF. Cox proportional hazards models were used to evaluate the association between AF incidence and oximetry-derived indices automatically generated from sleep recordings. Results: After a median (interquartile range) follow-up of 5.34 (3.3-8.0) years, 181 of 7,205 patients developed AF (130 were hospitalized for AF). After adjusting for confounders, including anthropomorphic data, alcohol intake, cardiac, metabolic and respiratory diseases, beta blocker/calcium channel blocker medications, type of sleep study, study site, and positive airway pressure adherence, AF risk was associated with increasing nocturnal hypoxemia (P trend = 0.004 for quartiles of percentage of recording time with oxygen saturation

Purpose:Less than 50% of patients with melanoma respond to anti–programmed cell death protein 1 (anti–PD-1), and this treatment can induce severe toxicity. Predictive markers are thus needed to improve the benefit/risk ratio of immune checkpoint inhibitors (ICI). Baseline tumor parameters such as programmed death ligand 1 (PD-L1) expression, CD8+ T-cell infiltration, mutational burden, and various transcriptomic signatures are associated with response to ICI, but their predictive values are not sufficient. Interaction between PD-1 and its main ligand, PD-L1, appears as a valuable target of anti–PD-1 therapy. Thus, instead of looking at PD-L1 expression only, we evaluated the predictive value of the proximity between PD-1 and its neighboring PD-L1 molecules in terms of response to anti–PD-1 therapy.Experimental Design:PD-1/PD-L1 proximity was assessed by proximity ligation assay (PLA) on 137 samples from two cohorts (exploratory n = 66 and validation n = 71) of samples from patients with melanoma treated with anti–PD-1±anti–CTLA-4. Additional predictive biomarkers, such as PD-L1 expression (MELscore), CD8+ cells density, and NanoString RNA signature, were also evaluated.Results:A PD-1/PD-L1 PLA model was developed to predict tumor response in an exploratory cohort and further evaluated in an independent validation cohort. This score showed higher predictive ability (AUC = 0.85 and 0.79 in the two cohorts, respectively) for PD-1/PD-L1 PLA as compared with other parameters (AUC = 0.71–0.77). Progression-free and overall survival were significantly longer in patients with high PLA values (P = 0.00019 and P < 0.0001, respectively).Conclusions:The proximity between PD-1 and PD-L1, easily assessed by this PLA on one formalin-fixed paraffin-embedded section, appears as a new biomarker of anti–PD-1 efficacy.

International audience

In the field of organic solar cells, lateral junction is a new concept. Moreover, the photovoltaic behavior is firstly observed for surprising long organic lateral junctions reaching 1.8 cm and the new operation mechanism dominated by trap-assisted recombination is proposed.

International audience; Manuscript word count: 1,374 "take home" message: Indices of sleep apnoea-related hypoxic burden and heart rate variability derived from full-night polysomnography might be useful for identifying sleep apnoea patients at risk for stroke.

Background Although COPD patients are at higher risk for aspiration when breathing spontaneously, no information is available on the risk for microaspiration in invasively ventilated COPD patients. The aim of our study was to determine the relationship between COPD and abundant microaspiration in intubated critically ill patients. Methods This was a retrospective analysis of prospectively collected data, provided by 3 randomized controlled trials on microaspiration in critically ill patients receiving invasive mechanical ventilation for more than 48 h. Abundant microaspiration was defined as the presence of pepsin and or alpha-amylase at significant levels in tracheal aspirates. In all study patients, pepsin and alpha-amylase were quantitatively measured in all tracheal aspirates collected during a 48-h period. COPD was defined using spirometry criteria. Results Among the 515 included patients, 70 (14%) had proven COPD. Pepsin and alpha-amylase were quantitatively measured in 3873 and 3764 tracheal aspirates, respectively. No significant difference was found in abundant microaspiration rate between COPD and non-COPD patients (62 of 70 patients (89%) vs 366 of 445 (82%) patients, p = 0.25). Similarly, no significant difference was found in abundant microaspiration of gastric contents (53% vs 45%, p = 0.28), oropharyngeal secretions (71% vs 71%, p = 0.99), or VAP (19% vs 22%, p = 0.65) rates between the two groups. No significant difference was found between COPD and non-COPD patients in duration of mechanical ventilation, ICU length of stay, or ICU mortality. Conclusions Our results suggest that COPD is not associated with increased risk for abundant microaspiration in intubated critically ill patients.

Objective To assess obstetric factors associated with hysterotomy extension among women undergoing a second-stage cesarean. Study design This 5-year retrospective cohort study (2013–2017) included all women with second-stage cesarean deliveries of live-born singleton fetuses in cephalic presentation at term. It took place at a tertiary center that practices delayed pushing. We performed univariable and multivariable logistic regression to assess the maternal, obstetric, and neonatal factors associated with hysterotomy extension mentioned in the surgical report. Operative time, postpartum hemorrhage, and maternal complications were also studied. Results Of the 3350 intrapartum cesareans, 2637 were performed at term for singleton fetuses in cephalic presentation: 747 (28.3%) during the second stage of labor, 83 (11.1%) of which were complicated by a hysterotomy extension. The median duration of the passive phase of the second stage did not differ between women with and without an extension (164 min versus 160 min, P = 0.85). No other second-stage obstetric characteristics, i.e., duration of the active phase, fetal head station, or fetal malposition, were associated with the risk of extension. Factors significantly associated with extension were the surgeon’s experience and forceps use during the cesarean. Women with an extension, compared to women without one, had a longer median operative time (49 min versus 32 min, Pp = 0.002 and 7.2% versus 2.4%, P = 0.03). Conclusion The risk of a hysterotomy extension does not appear to be associated with second-stage obstetric characteristics, including the duration of the passive phase of this stage. In our center, which practices delayed pushing, prolonging this passive phase beyond 2 hours does not increase the risk of hysterotomy extension in second-stage cesareans.

IntroductionA palliative approach to intensive care unit (ICU) patients with acute respiratory failure and a do-not-intubate order corresponds to a poorly evaluated target for non-invasive oxygenation treatments. Survival alone should not be the only target; it also matters to avoid discomfort and to restore the patient’s quality of life. We aim to conduct a prospective multicentre observational study to analyse clinical practices and their impact on outcomes of palliative high-flow nasal oxygen therapy (HFOT) and non-invasive ventilation (NIV) in ICU patients with do-not-intubate orders.Methods and analysisThis is an investigator-initiated, multicentre prospective observational cohort study comparing the three following strategies of oxygenation: HFOT alone, NIV alternating with HFOT and NIV alternating with standard oxygen in patients admitted in the ICU for acute respiratory failure with a do-not-intubate order. The primary outcome is the hospital survival within 14 days after ICU admission in patients weaned from NIV and HFOT. The sample size was estimated at a minimum of 330 patients divided into three groups according to the oxygenation strategy applied. The analysis takes into account confounding factors by modelling a propensity score.Ethics and disseminationThe study has been approved by the ethics committee and patients will be included after informed consent. The results will be submitted for publication in peer-reviewed journals.Trial registration numberNCT03673631