Empiric antimicrobial therapy for ventilator-associated pneumonia after brain injury

International audienceIssues regarding recommendations on empiric antimicrobial therapy for ventilator-associated pneumonia (VAP) have emerged in specific populations.To develop and validate a score to guide empiric therapy in brain-injured patients with VAP, we prospectively followed a cohort of 379 brain-injured patients in five intensive care units. The score was externally validated in an independent cohort of 252 brain-injured patients and its extrapolation was tested in 221 burn patients.The multivariate analysis for predicting resistance (incidence 16.4%) showed two independent factors: preceding antimicrobial therapy ≥48 h (p\textless0.001) and VAP onset ≥10 days (p\textless0.001); the area under the receiver operating characteristic curve (AUC) was 0.822 (95% CI 0.770-0.883) in the learning cohort and 0.805 (95% CI 0.732-0.877) in the validation cohort. The score built from the factors selected in multivariate analysis predicted resistance with a sensitivity of 83%, a specificity of 71%, a positive predictive value of 37% and a negative predictive value of 96% in the validation cohort. The AUC of the multivariate analysis was poor in burn patients (0.671, 95% CI 0.596-0.751).Limited-spectrum empirical antimicrobial therapy has low risk of failure in brain-injured patients presenting with VAP before day 10 and when prior antimicrobial therapy lasts \textless48 

Development of Randomized Trials in Adults with Medulloblastoma—The Example of EORTC 1634-BTG/NOA-23

From MDPI via Jisc Publications RouterHistory: accepted 2021-07-08, pub-electronic 2021-07-09Publication status: PublishedFunder: Deutsche Krebshilfe; Grant(s): 70113453Funder: Cancer Australia; Grant(s): 1165910Funder: CanTeen; Grant(s): noneFunder: KWF Kankerbestrijding; Grant(s): 2021-1/13555Funder: Ministère des Affaires Sociales et de la Santé; Grant(s): PHRC-K20-179Funder: Swiss Brain Tumor Foundation; Grant(s): none, none, noneMedulloblastoma is a rare brain malignancy. Patients after puberty are rare and bear an intermediate prognosis. Standard treatment consists of maximal resection plus radio-chemotherapy. Treatment toxicity is high and produces disabling long-term side effects. The sonic hedgehog (SHH) subgroup is highly overrepresented in the post-pubertal and adult population and can be targeted by smoothened (SMO) inhibitors. No practice-changing prospective randomized data have been generated in adults. The EORTC 1634-BTG/NOA-23 trial will randomize patients between standard-dose vs. reduced-dosed craniospinal radiotherapy and SHH-subgroup patients between the SMO inhibitor sonidegib (OdomzoTM, Sun Pharmaceuticals Industries, Inc., New York, USA) in addition to standard radio-chemotherapy vs. standard radio-chemotherapy alone to improve outcomes in view of decreased radiotherapy-related toxicity and increased efficacy. We will further investigate tumor tissue, blood, and cerebrospinal fluid as well as magnetic resonance imaging and radiotherapy plans to generate information that helps to further improve treatment outcomes. Given that treatment side effects typically occur late, long-term follow-up will monitor classic side effects of therapy, but also health-related quality of life, cognition, social and professional outcome, and reproduction and fertility. In summary, we will generate unprecedented data that will be translated into treatment changes in post-pubertal patients with medulloblastoma and will help to design future clinical trials

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Genome-wide Association Study of Change in Fasting Glucose over time in 13,807 non-diabetic European Ancestry Individuals

Type 2 diabetes (T2D) affects the health of millions of people worldwide. The identification of genetic determinants associated with changes in glycemia over time might illuminate biological features that precede the development of T2D. Here we conducted a genome-wide association study of longitudinal fasting glucose changes in up to 13,807 non-diabetic individuals of European descent from nine cohorts. Fasting glucose change over time was defined as the slope of the line defined by multiple fasting glucose measurements obtained over up to 14 years of observation. We tested for associations of genetic variants with inverse-normal transformed fasting glucose change over time adjusting for age at baseline, sex, and principal components of genetic variation. We found no genome-wide significant association (P < 5 x 10(-8)) with fasting glucose change over time. Seven loci previously associated with T2D, fasting glucose or HbA1c were nominally (P < 0.05) associated with fasting glucose change over time. Limited power influences unambiguous interpretation, but these data suggest that genetic effects on fasting glucose change over time are likely to be small. A public version of the data provides a genomic resource to combine with future studies to evaluate shared genetic links with T2D and other metabolic risk traits.Peer reviewe

Genome-wide Association Study of Change in Fasting Glucose over time in 13,807 non-diabetic European Ancestry Individuals

Type 2 diabetes (T2D) affects the health of millions of people worldwide. The identification of genetic determinants associated with changes in glycemia over time might illuminate biological features that precede the development of T2D. Here we conducted a genome-wide association study of longitudinal fasting glucose changes in up to 13,807 non-diabetic individuals of European descent from nine cohorts. Fasting glucose change over time was defined as the slope of the line defined by multiple fasting glucose measurements obtained over up to 14 years of observation. We tested for associations of genetic variants with inverse-normal transformed fasting glucose change over time adjusting for age at baseline, sex, and principal components of genetic variation. We found no genome-wide significant association (P < 5 × 10−8) with fasting glucose change over time. Seven loci previously associated with T2D, fasting glucose or HbA1c were nominally (P < 0.05) associated with fasting glucose change over time. Limited power influences unambiguous interpretation, but these da

Renforcement mécanique du verre (nouvelles compositions chimiques et dépôt de films minces élaborés par voie sol-gel)

Ce travail, articulé en deux parties, s inscrit dans une démarche exploratoire visant à améliorer la résistance mécanique du verre. Tout d abord, nous avons abordé la recherche de nouvelles compositions vitreuses à hautes propriétés mécaniques. Les compositions ont été synthétisées à l aide d un dispositif original développé au laboratoire opérant sous atmosphère contrôlée. Les verres ont été caractérisés en termes de propriétés mécaniques et de structure pour d identifier les paramètres gouvernant les propriétés mécaniques macroscopiques. Nous nous sommes intéressés dans la deuxième partie au dépôt sur la surface de films minces inorganiques élaborés par voie sol-gel (silice, alumine et zircone amorphes). Les échantillons ont été caractérisés par micro-indentation et micro-rayage. Des observations ont également été réalisées par microscopie à force atomique, dans le but de déterminer l influence du traitement thermique et de la composition sur ces propriétés.This work aims at improving mechanical resistance of glass. Two aspects of reinforcement have been studied. First, we focused on the research of new glassy compositions exhibiting high mechanical properties. The compositions were synthesized using an original home-made device. The mechanical characteristics were then determined, and an exploratory study of the structure was conducted in order to establish the role of the reticulation of the network. The second part deals with the mechanical reinforcement of the surface. Indeed, small defects existing on the surface often affect the strength of the whole piece of glass. To minimize this effect, we deposited inorganic thin films obtained via sol-gel process by a dip-coating method. This way, ordinary soda-lime silicate glass substrates were coated and then characterized both mechanically and morphologically, to determine the influence of thermal treatment, as well as composition, on mechanical properties.RENNES1-BU Sciences Philo (352382102) / SudocSudocFranceF

Enhancing Patient Care in Radiotherapy: Proof-of-Concept of a Monitoring Tool

Introduction: A monitoring tool, named Oncology Data Management (ODM), was developed in radiotherapy to generate structured information based on data contained in an Oncology Information System (OIS). This study presents the proof-of-concept of the ODM tool and highlights its applications to enhance patient care in radiotherapy. Material & Methods: ODM is a sophisticated SQL query which extracts specific features from the Mosaiq OIS (Elekta, UK) database into an independent structured database. Data from 2016 to 2022 was extracted to enable monitoring of treatment units and evaluation of the quality of patient care. Results: A total of 25,259 treatments were extracted. Treatment machine monitoring revealed a daily 11-treatement difference between two units. ODM showed that the unit with fewer daily treatments performed more complex treatments on diverse locations. In 2019, the implementation of ODM led to the definition of quality indicators and in organizational changes that improved the quality of care. As consequences, for palliative treatments, there was an improvement in the proportion of treatments prepared within 7 calendar days between the scanner and the first treatment session (29.1% before 2020, 40.4% in 2020 and 46.4% after 2020). The study of fractionation in breast treatments exhibited decreased prescription variability after 2019, with distinct patient age categories. Bi-fractionation once a week for larynx prescriptions of 35 × 2.0 Gy achieved an overall treatment duration of 47.0 ± 3.0 calendar days in 2022. Conclusions: ODM enables data extraction from the OIS and provides quantitative tools for improving organization of a department and the quality of patient care in radiotherapy

Efficacité des glucides fonctionnels raffinés associés à de la bentonite sur les performances de reproduction des truies en gestation nourries avec un aliment contenant de la zéaralénone et du déoxynivalénol

International audienceZearalenone (ZEN) and deoxynivalenol (DON) mycotoxins play a major role in decreasing fertility and increasing mortality and stillbirths in sows. The objective of this study was to evaluate effects of supplementation of refined functional carbohydrates (RFC) derived from enzymatically hydrolyzed Saccharomyces cerevisiae yeast combined with bentonite from insemination to d112 of gestation on reproductive performance of sows receiving gestation diets containing a mean of 290 μg/kg ZEN and 69 μg/kg DON. The study was conducted at a commercial sow farm. Three hundred and three sows (Landrace × Large White) were allocated to one of two treatments with or without RFC plus bentonite. The study began when estrus was detected and sows were inseminated, to d112 of gestation. Percentage fertility rate, percentage farrowing rate, sow mortality, and litter size (total, alive, stillborn and mummified) were measured. Data were analyzed using Minitab (version 17.0 for Windows), with the sow as the experimental unit. Treatment effects were considered significant at P ≤ 0.05 and showing a trend at P < 0.10. A trend in treatment effects was noted for fertility rate. Sows fed RFC + bentonite had a 93.4% fertility rate, compared to 87.5% in control-fed sows (P = 0.08). Treatment effects were also noted for farrowing rate and mortality rate. Sows fed RFC + bentonite had a 89.4% farrowing rate, compared to 79.6% in control-fed sows (P = 0.02). Sow mortality in the treatment group was 0.7%, compared to 5.3% in control-fed sows (P = 0.02). No significant treatment effects were noted for litter size. In conclusion, RFC + bentonite supplementation in sow diets containing moderate levels of DON and ZEN helps reduce the negative impacts of mycotoxins on reproductive performance and mortality in sows.Ces dernières années, la prévalence d'au moins une mycotoxine dans les aliments pour animaux ou leurs matières premières a atteint 88%, la prévalence de la zéaralénone (ZEN) et du déoxynivalénol (DON ou vomitoxine) étant respectivement (Gruber-Dorninger et al., 2019) de 45% et 64%. Les porcs sont plus sensibles aux mycotoxines alimentaires que les autres animaux d'élevage, en particulier les jeunes porcs et les animaux reproducteurs. La rentabilité d'une exploitation porcine dépend du nombre de porcs sevrés par truie et par an, qui dépend à son tour des performances de reproduction et de la santé des truies. Les mycotoxines zéaralénone et DON jouent un rôle majeur dans la diminution de la fertilité et l'augmentation de la mortalité et des mort-nés chez les truies. Les liants utilisés habituellement pour piéger les mycotoxines sont apparemment moins efficace contre le DON. Dans des études antérieures, un produit prébiotique à base de levure hydrolysée par voie enzymatique a pu bloquer les effets de cytotoxicité intestinale in vitro provoqués par des mycotoxines communes, dont le DON (Baines et al., 2011). De plus, chez les vaches laitières, ce prébiotique a bloqué le transfert de l'aflatoxine B1 du digesta au lait (Baines, 2014).L’étude présentée a été menée pour évaluer l'effet de glucides fonctionnels raffinés (RFC) dérivés de la levure Saccharomyces cerevisiae hydrolysée par voie enzymatique, combinés à de la bentonite (BGMAX™, ARM & HAMMER, USA), sur la performance reproductive de truies recevant des régimes de gestation contenant de la ZEN et du DON