Search

Resumen Antecedentes y objetivo La enfermedad microvascular (EMV) diabetica ha sido asociada con una fragilidad osea incrementada. El objetivo fue analizar la relacion entre la EMV y la microestructura trabecular -evaluada mediante el indice trabecular oseo (trabecular bone score, TBS)- en pacientes diabeticos tipo 2 (DM2). Adicionalmente, conocer la relacion entre la vitamina D y la EMV. Pacientes y metodos Diseno transversal analitico, que incluyo varones > 50 anos y mujeres postmenopausicas con DM2, participantes en una cohorte poblacional. Se clasifico como EMV+ la presencia de nefropatia, neuropatia y/o retinopatia. Fueron analizadas variables clinicas, de laboratorio, el TBS, la 25-hidroxivitamina D [25(OH)D] y la densidad mineral osea (DMO). Se realizaron analisis bivariable y multivariable. Resultados Fueron evaluados 361 pacientes (51,1% mujeres), de 63,8 (9) anos. De ellos, 92 tenian EMV, con un peor control metabolico, mayor duracion de la DM2, menor TBS (1,235 [0,1] vs. 1,287 [0,1]; p = 0,003) y menores niveles de 25(OH)D (18,3 [7] vs. 21,6 [8] ng/mL; p = 0,0001). No hubo diferencias entre EMV+ y EMV- en la DMO ni en los marcadores P1NP y β-CTX. Tras ajustar por confusores, incluyendo HbA1c y duracion de la DM2, el TBS en EMV+ fue 1,252 (IC 95% 1,230-1,274) vs. 1,281 (IC 95% 1,267-1,295) en EMV- (p = 0,034). La EMV se asocio a un nivel de 25(OH)D Conclusiones Los pacientes con EMV presentaron un TBS significativamente menor, tras ajustar por confusores. El analisis multivariable mostro asimismo una asociacion significativa entre un nivel bajo de 25(OH)D y la EMV prevalente.

Objectives : We implemented a project named MENINGSTOP in three countries of North Africa (Algeria, Morocco and Tunisia). The main objective was to use real-time PCR to detect, identify and type the three main agents (Neisseria meningitidis, Streptococcus pneumoniae and Haemophilus influenzae) responsible for invasive bacterial infections (IBI). Methods : The protocol of WHO and US CDC for real-time PCR was used to detect and type the three bacterial agents in clinical samples. We also designated two quality exercises using an external interlaboratory study and cross-testing of 10% of randomly selected samples. Results : Among the 752 samples tested, 18% were positive for one of the three agents. N. meningitidis was the most frequent globally reaching 9% of all samples (7% to 17% range) followed by S. pneumoniae 8% of all samples (6% to 15%). Group B meningococci was the most frequent (74% of all positive samples for meningococci and ranging from 50% to 90%). Quality assurance showed >85% correlation scores. Conclusions : Real-time PCR can help improving epidemiological surveillance. Data confirm the prevalence of meningococci B. Our project add a reliable tool to enhance surveillance and to help decision making in vaccination strategies against IBI.

The objective of this work is to compare the efficiency of three computational intelligence techniques: Artificial Neural Networks (ANNs), Support Vector Machines (SVMs) and Adaptive Neuro-Fuzzy Inference System (ANFIS) to model the dynamic adsorption of organic pollutants on activated carbon. A comparison study was enhanced using five models: ANN with conventional transfer functions, ANN with new transfer function called “SPOCU”, SVM, SVM hybrid with Dragonfly optimisation algorithm (SVM-DA) and ANFIS. A set of data points, collected from scientific papers containing the dynamic adsorption kinetics of adsorption on activated carbon, was used in the modelling process. The studied parameters were molar mass, initial concentration, flow rate, bed height, BET surface area, time and concentration of non-dimensional effluents. Overall, the developed model was able to accurately estimate 11,763 experimental data points gathered from the literature. The performance of the optimised models has been evaluated using different metrics between the experimental and the predicted data. Results show that SVM-DA model can estimate accurately the dynamic adsorption of organic pollutants on activated carbon against the other tested models. Also a graphical user interface is developed in this paper in order to keep the traceability of the estimated results.

One of the most important developing cell types in any biological system is the gamete (sperm and egg). The transmission of phenotypes and optimally adapted physiology to subsequent generations is in large part controlled by gametogenesis. In contrast to genetics, the environment actively regulates epigenetics to impact the physiology and phenotype of cellular and biological systems. The integration of epigenetics and genetics is critical for all developmental biology systems at the cellular and organism level. The current review is focused on the role of epigenetics during gametogenesis for both the spermatogenesis system in the male and oogenesis system in the female. The developmental stages from the initial primordial germ cell through gametogenesis to the mature sperm and egg are presented. How environmental factors can influence the epigenetics of gametogenesis to impact the epigenetic transgenerational inheritance of phenotypic and physiological change in subsequent generations is reviewed., How environmental factors can influence the epigenetics of gametogenesis to impact the epigenetic transgenerational inheritance of phenotypic and physiological change in subsequent generations is reviewed.

Background It is challenging to detect posterior circulation strokes in patients presenting to the emergency department (ED) with acute dizziness. The current approach uses a combinatorial head-impulse, nystagmus, and test-of-skew method and is sensitive enough to differentiate central causes from peripheral ones. However, it is difficult to perform and underused. Further, magnetic resonance imaging (MRI) of the brain is not always available and can have low sensitivity for detecting posterior circulation strokes. Objectives We evaluated the feasibility and utility of the bucket test (BT), which measures the difference between patient's subjective perception of the visual vertical and the true vertical, as a screening tool for stroke in patients presenting to the ED with acute dizziness. Methods In this work, we prospectively enrolled 81 patients that presented to our academic medical center ED with dizziness as their chief complaint. The BT was performed 3 times for every patient. Results Seventy-one patients met the study criteria and were included in the analysis. Ten patients were excluded because of a history of drug-seeking behavior. There were no reported difficulties performing the BT. Six patients (8%) were diagnosed with ischemic stroke on MRI and 1 additional patient was diagnosed with transient ischemic attack and found to have a stroke on subsequent MRI. All 7 patients with dizziness attributed to cerebrovascular etiology had an abnormal BT, resulting in a sensitivity of 100% (95% confidence interval [CI] 59–100%). The specificity of the BT was 38% (95% CI 24–52%). The positive predictive value of the BT for detecting stroke was 18% (95% CI 15–21%). Conclusions The BT is an easy, cheap, safe, and quick test that is feasible and sensitive to screen acutely dizzy patients for stroke in the ED.

International audience; OBJECTIVES: To evaluate performances of the rapid multiplex PCR assay BioFire FilmArray Pneumonia Panel (FA-PP) for detection of bacterial pathogens and antibiotic resistance genes in sputum, endotracheal aspirate (ETA) and bronchoalveolar lavage (BAL) specimens. METHODS: This prospective observational study was conducted in 11 French university hospitals (July to December 2018) and assessed performance of FA-PP by comparison with routine conventional methods. RESULTS: A total of 515 respiratory specimens were studied, including 58 sputa, 217 ETA and 240 BAL. The FA-PP detected at least one pathogen in 384 specimens, yielding an overall positivity rate of 74.6% (384/515). Of them, 353 (68.5%) specimens were positive for typical bacteria while eight atypical bacteria and 42 resistance genes were found. While identifying most bacterial pathogens isolated by culture (374/396, 94.4%), the FA-PP detected 294 additional species in 37.7% (194/515) of specimens. The FA-PP demonstrated positive percentage agreement and negative percentage agreement values of 94.4% (95% CI 91.7%-96.5%) and 96.0% (95% CI 95.5%-96.4%), respectively, when compared with culture. Of FA-PP false-negative results, 67.6% (46/68) corresponded to bacterial species not included in the panel. At the same semi-quantification level (in DNA copies/mL for FA-PP versus in CFU/mL for culture), the concordance rate was 43.4% (142/327) for culture-positive specimens with FA-PP reporting higher semi-quantification of ≥1 log(10) in 48.6% (159/327) of cases. Interestingly, 90.1% of detected bacteria with ≥10(6) DNA copies/mL grew significantly in culture. CONCLUSIONS: FA-PP is a simple and rapid molecular test that could complement routine conventional methods for improvement of diagnosis accuracy of pneumonia.

Background and Aim: The coronavirus disease 2019 (COVID-19) vaccine helps to develop immunity to SARS-CoV-2, the virus that causes COVID-19, in most cases preventing the disease. Although various brands of vaccines work in different modes, all COVID-19 vaccines prompt an immune reaction to make the body remembers how to protect from the virus in the future. The present study aims to evaluate the safety and the immune response for mixing of Sputnik V and AstraZeneca COVID-19 vaccines on mice. Materials and Methods: Our experimental study was performed on mice weighing on average of 20 g, selected by random allocation. The mice were divided into four groups of 12. Group one received a single dose of 0.5 ml Sputnik V COVID-19 vaccine, group two received two doses of 0.5 ml AstraZeneca COVID-19 vaccine, group three received two doses of 0.5 ml Sputnik V together with 0.5 ml AstraZeneca COVID-19 vaccine and group four received two doses of 0.5 ml of 0.9 % NaCl. Results: Our study shows that mixing of Sputnik V and AstraZeneca COVID-19 vaccines is safe and induces good immunity for mice. Conclusion: Mixing of Sputnik V and AstraZeneca COVID-19 vaccines creates no problems and provides good immunity to mice and may be an interesting technique to help to overcome shortcomings of one or the other vaccine. Further toxicity studies are required to assess potential hazards for humans to evaluate the histopathological characteristics.

Introduction: vancomycin-resistant Enterococcus faecium (VREfm) is a major public health problem worldwide. The aim of our study was to determine the microbiological, epidemiological and molecular characteristics of VREfm isolated in north-central, eastern and western Algeria. Methodology: a collection of 48 VREfm isolated from September 2010 to April 2017 in several Algerian hospitals were studied. Minimum inhibitory concentrations (MICs) were determined by E-test method according to CLSI guidelines. the detection of van genotype of all strains was performed by PCR. Clonal relationship of five VREfm targeted by region were characterized using multilocus sequence typing (MLST). Results: All isolates have multidrug-resistance (MDR) and were resistant to at least five classes of antibiotics; however, all were susceptible to tigecycline and daptomycin with MIC50 at 0.094 µg/mL and 2 µg/mL respectively. All strains belonged to vanA genotype and have high level of resistance to vancomycin and teicoplanin. MLST revealed two sequence types (STs): ST80 (from the four regions of Algeria) and ST789, both belonging to the former hospital-adapted clonal complex CC17. Conclusions: the alarming dissemination of MDR E. faecium vanA and the ST80 in several regions of Algeria suggest a clonal spread of VREfm strains, which urgently require implementation of adequate infection control measures.

Purpose The SARS-CoV-2 infection can lead to a severe acute respiratory distress syndrome (ARDS) with prolonged mechanical ventilation and high mortality rate. Interestingly, COVID-19-associated ARDS share biological and clinical features with sepsis-associated immunosuppression since lymphopenia and acquired infections associated with late mortality are frequently encountered. Mechanisms responsible for COVID-19-associated lymphopenia need to be explored since they could be responsible for delayed virus clearance and increased mortality rate among intensive care unit (ICU) patients. Methods A series of 26 clinically annotated COVID-19 patients were analyzed by thorough phenotypic and functional investigations at days 0, 4, and 7 after ICU admission. Results We revealed that, in the absence of any difference in demographic parameters nor medical history between the two groups, ARDS patients presented with an increased number of myeloid-derived suppressor cells (MDSC) and a decreased number of CD8pos effector memory cell compared to patients hospitalized for COVID-19 moderate pneumonia. Interestingly, COVID-19-related MDSC expansion was directly correlated to lymphopenia and enhanced arginase activity. Lastly, T cell proliferative capacity in vitro was significantly reduced among COVID-19 patients and could be restored through arginine supplementation. Conclusions The present study reports a critical role for MDSC in COVID-19-associated ARDS. Our findings open the possibility of arginine supplementation as an adjuvant therapy for these ICU patients, aiming to reduce immunosuppression and help virus clearance, thereby decreasing the duration of mechanical ventilation, nosocomial infection acquisition, and mortality. Supplementary Information The online version contains supplementary material available at 10.1007/s10875-020-00920-5.

Summary Background Chimeric antigen receptor (CAR) T-cell therapy can induce side-effects such as cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome (ICANS), which often require intensive care unit admission. The aim of this study was to describe management of critically ill CAR T-cell recipients in intensive care. Methods This international, multicentre, observational cohort study was done in 21 intensive care units in France, Spain, the USA, the UK, Russia, Canada, Germany, and Austria. Eligible patients were aged 18 years or older; had received CAR T-cell therapy in the past 30 days; and had been admitted to intensive care for any reason. Investigators retrospectively included patients admitted between Feb 1, 2018, and Feb 1, 2019, and prospectively included patients admitted between March 1, 2019, and Feb 1, 2020. Demographic, clinical, laboratory, treatment, and outcome data were extracted from medical records. The primary endpoint was 90-day mortality. Factors associated with mortality were identified using a Cox proportional hazard model. Findings 942 patients received CAR T-cell therapy, of whom 258 (27%) required admission to intensive care and 241 (26%) were included in the analysis. Admission to intensive care was needed within median 4·5 days (IQR 2·0–7·0) of CAR T-cell infusion. 90-day mortality was 22·4% (95% CI 17·1–27·7; 54 deaths). At initial evaluation on admission, isolated cytokine release syndrome was identified in 101 patients (42%), cytokine release syndrome and ICANS in 93 (39%), and isolated ICANS in seven (3%) patients. Grade 3–4 cytokine release syndrome within 1 day of admission to intensive care was found in 50 (25%) of 200 patients and grade 3–4 ICANS in 38 (35%) of 108 patients. Bacterial infection developed in 30 (12%) patients. Life-saving treatments were used in 75 (31%) patients within 24 h of admission to intensive care, primarily vasoactive drugs in 65 (27%) patients. Factors independently associated with 90-day mortality by multivariable analysis were frailty (hazard ratio 2·51 [95% CI 1·37–4·57]), bacterial infection (2·12 [1·11–4·08]), and lifesaving therapy within 24 h of admission (1·80 [1·05–3·10]). Interpretation Critical care management is an integral part of CAR T-cell therapy and should be standardised. Studies to improve infection prevention and treatment in these high-risk patients are warranted. Funding Groupe de Recherche Respiratoire en Reanimation Onco-Hematologique.

Introduction: The aim of this study was to investigate the drug-resistance and the molecular characterization of carbapenemases, ESBL, and aminoglycoside-modifying enzymes among Acinetobacter baumannii clinical isolates in Algerian hospitals. Methodology: A total of 92 A. baumannii isolates were collected between 2012 and 2016. Antimicrobial susceptibility testings were performed for β-lactams, aminoglycosides, fluoroquinolones, trimethoprim-sulfamethoxazole, rifampicin and colistin. The phenotypic characterization of β-lactamases was investigated. For 30 randomly targeted strains, the carriage of the carbapenemases, ESBL and aminoglycoside-modifying enzymes -encoding genes was determined by PCR. Sequencing was carried out for carbapenemases and ESBL genes. Results: Most of the 92 isolates studied were recovered from hospitalized patients (93.5%) and were mainly from intensive care units (51.1%) and orthopedics (19.6%). The strains were collected primarily from low respiratory tract (33.7%), wounds (23.9%) and urine (16.3%). Multidrug-resistant A. baumannii strains were prevalent (96.7%). High rates of resistance were observed for almost all antibiotics tested (>70%) excluding rifampicin (7.6%) and colistin (5.4%). For the five colistin-resistant strains, MICs ranged between 4 and 128 µg/mL. Positive MBL (83.7%) and ESBL (23.9%) strains were identified. Regarding β-lactams, the blaNDM and both blaSHV and blaCTX-M1 genes were detected in five and two strains respectively. Sequencing of the genes revealed the presence of blaNDM-1, blaCTX-M-15, and blaSHV-33. For aminoglycosides, aac(6’)-Ib, ant(2’’)-I and aph(3’)-VI genes were detected in three, seven and six strains respectively. Conclusions: Here, we report the first co-occurrence of extended-spectrum β-lactamases SHV-33 and CTX-M-15, the carbapenemase NDM-1 and the emergence of colistin-resistant A. baumannii in Algerian hospitals.

Introduction. Des études ont fait émerger l’existence de risque de prédiabète chez les patients qui ont une combinaison, profil glycémique normal et une glycémie à 1 heure supérieure à 1,55 g/L. Nous avons étudié les effets des combinaisons glycémie 1 heure (Gly 1h) après une hyperglycémie provoquée par voie orale HGPO avec un profil glycémique normal. Méthode. Une HGPO standardisée a été réalisée chez 100 femmes obèses. 46 avaient un profil glycémique normal. Une GAJ

Corrosion inhibitors based on environmentally friendly and harmless products are currently being studied and developed. The corrosion inhibition properties of caffeine (1,3,7-trimethylxanthine) on ...

STUDY QUESTION Which transcriptional program triggers sex differentiation in bipotential gonads and downstream cellular events governing fetal testis and ovary development in humans? SUMMARY ANSWER The characterization of a dynamically regulated protein-coding and non-coding transcriptional landscape in developing human gonads of both sexes highlights a large number of potential key regulators that show an early sexually dimorphic expression pattern. WHAT IS KNOWN ALREADY Gonadal sex differentiation is orchestrated by a sexually dimorphic gene expression program in XX and XY developing fetal gonads. A comprehensive characterization of its non-coding counterpart offers promising perspectives for deciphering the molecular events underpinning gonad development and for a complete understanding of the etiology of disorders of sex development in humans. STUDY DESIGN, SIZE, DURATION To further investigate the protein-coding and non-coding transcriptional landscape during gonad differentiation, we used RNA-sequencing (RNA-seq) and characterized the RNA content of human fetal testis (N = 24) and ovaries (N = 24) from 6 to 17 postconceptional week (PCW), a key period in sex determination and gonad development. PARTICIPANTS/MATERIALS, SETTING, METHODS First trimester fetuses (6–12 PCW) and second trimester fetuses (13–14 and 17 PCW) were obtained from legally induced normally progressing terminations of pregnancy. Total RNA was extracted from whole human fetal gonads and sequenced as paired-end 2 × 50 base reads. Resulting sequences were mapped to the human genome, allowing for the assembly and quantification of corresponding transcripts. MAIN RESULTS AND THE ROLE OF CHANCE This RNA-seq analysis of human fetal testes and ovaries at seven key developmental stages led to the reconstruction of 22 080 transcripts differentially expressed during testicular and/or ovarian development. In addition to 8935 transcripts displaying sex-independent differential expression during gonad development, the comparison of testes and ovaries enabled the discrimination of 13 145 transcripts that show a sexually dimorphic expression profile. The latter include 1479 transcripts differentially expressed as early as 6 PCW, including 39 transcription factors, 40 long non-coding RNAs and 20 novel genes. Despite the use of stringent filtration criteria (expression cut-off of at least 1 fragment per kilobase of exon model per million reads mapped, fold change of at least 2 and false discovery rate adjusted P values of less than LARGE-SCALE DATA Raw data files (fastq) and a searchable table (.xlss) containing information on genomic features and expression data for all refined transcripts have been submitted to the NCBI GEO under accession number GSE116278. LIMITATIONS, REASONS FOR CAUTION The intrinsic nature of this bulk analysis, i.e. the sequencing of transcripts from whole gonads, does not allow direct identification of the cellular origin(s) of the transcripts characterized. Potential cellular dilution effects (e.g. as a result of distinct proliferation rates in XX and XY gonads) may account for a few of the expression profiles identified as being sexually dimorphic. Finally, transcriptome alterations that would result from exposure to pre-abortive drugs cannot be completely excluded. Although we demonstrated the high quality of the sorted cell populations used for experimental validations using quantitative RT-PCR, it cannot be totally excluded that some germline expression may correspond to cell contamination by, for example, macrophages. WIDER IMPLICATIONS OF THE FINDINGS For the first time, this study has led to the identification of 1000 protein-coding and non-coding candidate genes showing an early, sexually dimorphic, expression pattern that have not previously been associated with sex differentiation. Collectively, these results increase our understanding of gonad development in humans, and contribute significantly to the identification of new candidate genes involved in fetal gonad differentiation. The results also provide a unique resource that may improve our understanding of the fetal origin of testicular and ovarian dysgenesis syndromes, including cryptorchidism and testicular cancers. STUDY FUNDING/COMPETING INTEREST(S) This work was supported by the French National Institute of Health and Medical Research (Inserm), the University of Rennes 1, the French School of Public Health (EHESP), the Swiss National Science Foundation [SNF n° CRS115_171007 to B.J.], the French National Research Agency [ANR n° 16-CE14-0017-02 and n° 18-CE14-0038-02 to F.C.], the Medical Research Council [MR/L010011/1 to P.A.F.] and the European Community’s Seventh Framework Programme (FP7/2007-2013) [under grant agreement no 212885 to P.A.F.] and from the European Union’s Horizon 2020 Research and Innovation Programme [under grant agreement no 825100 to P.A.F. and S.M.G.]. There are no competing interests related to this study.

Background: The urinary tract stone disease is a common problem. Dual energy CT with advanced post processing techniques gives anatomical information as size, site of the stone as well as its chemical composition which alter the clinical management. Objective: This study was aimed at studying the role of dual energy computed tomography in characterization of renal stones. Patients and methods: This study was carried out at the private radiology center throughout the period from January 2020 to January 2021 included 48 patients with renal stones. In this study, renal stones were more common in men (66.7 %) than in women (30.3%). The age of our selected patients ranged from 24 to 55 years with a mean of 42 years. The most affected age group was from 24-44 years (24 cases) represented 50% of the cases. Results: The average age of the studied group was (42.1±7.6), the most common presentation symptoms was loin pain (75.0%) followed by hematuria (18.8 %) then nausea& vomiting (4.2%) and fever (2.0%).Dual energy CT had 88.9% ability to truly detect uric from non-uric acid stones with (97.9%) accuracy, (100.0%) ability to exclude non uric stones (specificity), (100.0%) predictive value positive and (97.5%) predictive value negative with (50.0%) prevalence and (35.0%) likelihood positive ratio. Conclusion: It could be concluded that dual energy CT has been shown to be effective for characterizing chemical composition of the urinary stones, dual energy CT not well established enough to be used in clinical practice, but it will replace helical non contrast CT as the standard imaging modality for urinary calculi.

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.

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

Viral hepatitis C is an inflammation caused by a virus of type C (HCV) that can lead to progressive liver failure. An immune response to eliminate the virus can cause severe deformities such as cirrhosis, hepatocellular carcinoma and even death. The aim of this research is to study the HCV-complications’ evolution and show how the treatment’s administration can act to reduce the risk of the transmission, the complexity and the severity of the disease and therefore the costs. Firstly, the model’s formulation is proposed. Then, the model solution’s existence and uniqueness are discussed. Thereafter, the stability analysis of the proposed model is presented. Finally, numerical simulations are presented to support the effectiveness of the theoretical analysis and to prove the positive effect of early treatment on the evolution of HCV-complications.

Summary Background Staphylococcus aureus remains a common cause of ventilator-associated pneumonia, with little change in incidence over the past 15 years. We aimed to evaluate the efficacy of suvratoxumab, a monoclonal antibody targeting the α toxin, in reducing the incidence of S aureus pneumonia in patients in the intensive care unit (ICU) who are on mechanical ventilation. Methods We did a multicentre, randomised, double-blind, placebo-controlled, parallel-group, phase 2 pilot trial at 31 hospitals in Belgium, the Czech Republic, France, Germany, Greece, Hungary, Portugal, Spain, and Switzerland. Eligible patients were in the ICU, aged ≥18 years, were intubated and on mechanical ventilation, were positive for S aureus colonisation of the lower respiratory tract, as assessed by quantitative PCR (qPCR) analysis of endotracheal aspirate, and had not been diagnosed with new-onset pneumonia. Patients were excluded if they had confirmed or suspected acute ongoing staphylococcal disease; had received antibiotics for S aureus infection for more than 48 h within 72 h of randomisation; had a Clinical Pulmonary Infection Score of 6 or higher; had an acute physiology and chronic health evaluation II score of 25 or higher with a Glasgow coma scale (GCS) score of more than 5, or an acute physiology and chronic health evaluation II score of at least 30 with a GCS score of 5 or less; had a Sequential Organ Failure Assessment score of 9 or higher; or had active pulmonary disease that would impair the ability to diagnose pneumonia. Colonised patients were randomly assigned (1:1:1), by use of an interactive voice or web response system, to receive either a single intravenous infusion of suvratoxumab 2000 mg, suvratoxumab 5000 mg, or placebo. Randomisation was done in blocks of size four, stratified by country and by whether patients had received systemic antibiotics for S aureus infection. Patients, investigators, and study staff involved in the treatment or clinical evaluation of patients were masked to patient assignment. The primary efficacy endpoint was the incidence of S aureus pneumonia at 30 days, as determined by a masked independent endpoint adjudication committee, in all patients who received their assigned treatment (modified intention-to-treat [ITT] population). Primary safety endpoints were the incidence of treatment-emergent adverse events at 30 days, 90 days, and 190 days after treatment, and the incidence of treatment-emergent serious adverse events, adverse events of special interest, and new-onset chronic disease at 190 days after treatment. All primary safety endpoints were assessed in the modified ITT population. This trial is registered with ClinicalTrials.gov ( NCT02296320 ) and the EudraCT database (2014-001097-34). Findings Between Oct 10, 2014, and April 1, 2018, 767 patients were screened, of whom 213 patients with confirmed S aureus colonisation of the lower respiratory tract were randomly assigned to the suvratoxumab 2000 mg group (n=15), the suvratoxumab 5000 mg group (n=96), or the placebo group (n=102). Two patients in the placebo group did not receive treatment after randomisation because their clinical conditions changed and they no longer met the eligibility criteria for dosing. As adjudicated by the data monitoring committee at an interim analysis, the suvratoxumab 2000 mg group was discontinued on the basis of predefined pharmacokinetic criteria. At 30 days after treatment, 17 (18%) of 96 patients in the suvratoxumab 5000 mg group and 26 (26%) of 100 patients in the placebo group had developed S aureus pneumonia (relative risk reduction 31·9% [90% CI −7·5 to 56·8], p=0·17). The incidence of treatment-emergent adverse events at 30 days were similar between the suvratoxumab 5000 mg group (87 [91%]) and the placebo group (90 [90%]). The incidence of treatment-emergent serious adverse events at 30 days were also similar between the suvratoxumab 5000 mg group (36 [38%]) and the placebo group (32 [32%]). No significant difference in the incidence of treatment-emergent adverse events between the two groups at 90 days (89 [93%] in the suvratoxumab 5000 mg group vs 92 [92%] in the placebo group) and at 190 days (93 [94%] vs 93 [93%]) was observed. 40 (40%) patients in the placebo group and 50 (52%) in the suvratoxumab 5000 mg group had a serious adverse event at 190 days. In the suvratoxumab 5000 mg group, one (1%) patient reported at least one treatment-emergent serious adverse event related to treatment, two (2%) patients reported an adverse event of special interest, and two (2%) reported a new-onset chronic disease. Interpretation In patients in the ICU receiving mechanical ventilation with qPCR-confirmed S aureus colonisation of the lower respiratory tract, the incidence of S aureus pneumonia at 30 days was not significantly lower following treatment with 5000 mg suvratoxumab than with placebo. Despite these negative results, monoclonal antibodies still represent one promising therapeutic option to reduce antibiotic consumption that require further exploration and studies. Funding AstraZeneca, with support from the Innovative Medicines Initiative Joint Undertaking.

INTRODUCTION AND OBJECTIVEPost-COVID syndrome (PCS) is a poorly-known entity. Underlying low-grade inflammation (LGI) has been theorized as one of its pathophysiological mechanisms. We aimed to investigate a possible relationship between PCS and an increase in inflammation markers, in a sex-stratified analysis.PARTICIPANTS AND METHODSMild cases of COVID-19 according to the WHO classification followed-up in a Primary Care Center, were included. We collected epidemiological data (age, sex, body mass index -BMI-, smoking, and comorbidities -Charlson index-), variables of the acute COVID-19 episode, and data at 3 months of follow-up (clinical manifestations and inflammatory markers). Serum C-reactive protein (CRP), neutrophil and lymphocyte counts, neutrophil/lymphocyte ratio (NLR), lactate dehydrogenase (LDH), ferritin, fibrinogen, and D-dimer levels were analyzed. Low-grade inflammation (LGI) was defined as serum CRP between >0.3 and RESULTSWe analyzed 121 subjects with mild COVID-19 (56.2% women; mean age 46 years). The most common symptom in the acute episode was fever (60.3%), while it was fatigue in PCS (42.8%). Prevalence of PCS was 35.8% in women and 20.8% in men (p = 0.07).In women, after controlling for age, BMI, smoking, and comorbidities, the D1, D3, and D4 indices were consistently associated with PCS, with ORs of 5.14 (95% CI, 1.6-16.4), 4.20 (95% CI, 1.3-13.3), and 4.12 (95% CI, 1.3-13.1), respectively; in patients with post-COVID anosmia and ageusia, neutrophils were significantly elevated (3.43±0.3 vs 2.58±0.1; p = 0.014, and 3.89±0.3 vs 2.59±0.1; p = 0.002,respectively), after adjusting for confounders.In men, the D2 and D5 indices were associated with PCS, with adjusted ORs of 10.1 (95% CI, 1.2-85) and 17.5 (95% CI, 2-153), respectively. Furthermore, serum CRP in the LGI range was associated with PCS [adjusted OR=12.9 (95% CI, 1.3-121)], and in post-COVID persistent fatigue, the neutrophil count was significantly elevated (4.68±0.6 vs 3.37±0.1; p = 0.041), after controlling for confounders.CONCLUSIONSConsistent associations among PCS, anosmia, ageusia, and fatigue, with slight -but significant-elevated levels of inflammatory markers, have been observed. The neutrophil count was the most frequently involved marker. Sex-stratified analyses showed relevant differences between women and men concerning PCS and serum inflammatory markers.

International audience; Background and aims: Hypercholesterolemia is a major risk factor for atherosclerosis and cardiovascular diseases. Although resistant to hypercholesterolemia, the mouse is a prominent model in cardiovascular research. To assess the contribution of bile acids to this protective phenotype, we explored the impact of a 2-week-long dietary cholesterol overload on cholesterol and bile acid metabolism in mice. Methods: Bile acid, oxysterol, and cholesterol metabolism and transport were assessed by quantitative real-time PCR, western blotting, GC-MS/MS, or enzymatic assays in the liver, the gut, the kidney, as well as in the feces, the blood, and the urine. Results: Plasma triglycerides and cholesterol levels were unchanged in mice fed a cholesterol-rich diet that contained 100-fold more cholesterol than the standard diet. In the liver, oxysterol-mediated LXR activation stimulated the synthesis of bile acids and in particular increased the levels of hydrophilic muricholic acids, which in turn reduced FXR signaling, as assessed in vivo with Fxr reporter mice. Consequently, biliary and basolateral excretions of bile acids and cholesterol were increased, whereas portal uptake was reduced. Furthermore, we observed a reduction in intestinal and renal bile acid absorption. Conclusions: These coordinated events are mediated by increased muricholic acid levels which inhibit FXR signaling in favor of LXR and SREBP2 signaling to promote efficient fecal and urinary elimination of cholesterol and neo-synthesized bile acids. Therefore, our data suggest that enhancement of the hydrophilic bile acid pool following a cholesterol overload may contribute to the resistance to hypercholesterolemia in mice. This work paves the way for new therapeutic opportunities using hydrophilic bile acid supplementation to mitigate hypercholesterolemia.

Introduction and importance Neuroendocrine carcinoma of the gallbladder is rare and aggressive, its diagnosis is based on pathologic and immunohistochemical examination, currently there is no standard treatment for this tumor. Its concomitant occurrence with adenocarcinoma of the sigmoid colon is exceptional. Case presentation This case report describes a rare case of neuroendocrine carcinoma of the gallbladder that occurred concomitantly with sigmoid colon adenocarcinoma. The diagnosis of neuroendocrine carcinoma was established postoperatively by pathological and immunohistochemical examination. The biopsy of the colonic process confirmed the preoperative diagnosis. A laparotomy found a vesicular fundus process, peri-hilar adenopathy, metastasis of the liver segment V, and a sigmoid colon process. The patient underwent a cholecystectomy extended to segments IVb and V, with lymph node dissection and sigmoid colectomy. The postoperative follow-up was uneventful, and the length of hospitalization was seven days. The patient is currently undergoing adjuvant chemotherapy. Discussion Neuroendocrine carcinoma of the gallbladder is extremely rare, with few case reports, its occurrence concomitantly with adenocarcinoma of the sigmoid colon is exceptional. Histology and immunohistochemistry confirm the diagnosis, surgery is essential in the management of patients affected by this tumor. The presence of synchronous metastases causes doubt about their primitive, hence the primordial place of surgery and histological examination to adopt adequate management of the patients. Conclusion We underline the rarity of this neuroendocrine tumor and the importance of histology and surgery in its management., Highlights • Neuroendocrine carcinoma of the gallbladder is a rare and aggressive tumor usually diagnosed at an advanced stage. • The patient presented with a vague abdominal pain and bleeding per rectum. • The final diagnosis is made upon histological and immunohistochemical examination. • The concomitant occurrence neuroendocrine neoplasm of the gallbladder and adenocarcinoma of the sigmoid is exceptional.

espanolLos sindromes linfoproliferativos engloban una gran variedad de subtipos cuyo diagnostico y abordaje difiere en funcion del subtipo. El diagnostico de los sindromes linfoproliferativos se basa en criterios que abarcan tanto clinica como analitica. Algunas de las pruebas solo pueden realizarse desde el Servicio de Hematologia, por lo que la sospecha a partir de la clinica es fundamental en atencion primaria para completar estudio en el hospital. El tratamiento varia en funcion del subtipo de sindrome linfoproliferativo: desde tratamiento conservador en determinados subtipos asintomaticos hasta quimioterapia. En atencion primaria es fundamental sospechar dichas patologias, por lo que es importante el conocimiento de la clinica a partir de una buena anamnesis y exploracion fisica. EnglishThe lymphoproliferative syndromes include a wide variety of subtypes whose diagnosis and management vary depending on the subtype. The diagnosis of lymphoproliferative syndromes is based on criteria that include both clinical and analytical. Some of the tests can only be performed from the Hematology Service, so the suspicion from the clinic is essential in Primary Care to complete a hospital-level study. The treatment will vary depending on the subtype of lymphoproliferative syndrome and may range from conservative treatment in certain asymptomatic subtypes to chemotherapy. At Primary Care level it is basic to suspect such pathologies, being important the knowledge of the clinic with a good anamnesis and physical examination.

The optimal timing of cardiac surgery in infective endocarditis (IE) remains debated: Early surgery decreases the risk of embolism, and heart failure, but is associated with an increased rate of positive valve culture. To determine the determinants, and the consequences, of positive valve culture when cardiac surgery is performed during the acute phase of IE, we performed a retrospective study of adult patients who underwent cardiac surgery for definite left-sided IE (Duke Criteria), in two referral centres. During the study period (2002-2016), 148 patients fulfilled inclusion criteria. Median age was 65 years [interquartile range, 53-73], male-to-female ratio was 2.9 (110/38). Cardiac surgery was performed after 14 days [5-26] of appropriate antibiotics. Valve cultures returned positive in 46 cases (31.1%). Factors independently associated with positive valve culture were vegetation size ≥ 10 mm (OR 2.83 [1.16-6.89], P = 0.022) and < 14 days of appropriate antibacterial treatment before surgery (OR 4.68 [2.04-10.7], P < 0.001). Positive valve culture was associated with increased risk of postoperative acute respiratory distress syndrome (37.0% vs. 15.7%, P = 0.008) but was associated neither with an increased risk of postoperative relapse nor with the need for additional cardiac surgery. Duration of appropriate antibacterial treatment and vegetation size are independently predictive of positive valve culture in patients operated during the acute phase of IE. Positive valve culture is associated with increased risk of postoperative acute respiratory distress syndrome.

Aim To assess the neurological prognosis of comatose survivors of cardiac arrest by early transcranial Doppler sonography (TCD). Methods This was a prospective study performed between May 2016 and October 2017 in a medical intensive care unit (ICU) and a cardiac ICU of a university teaching hospital. All patients older than 18 years who were successfully resuscitated from an out-of-hospital cardiac arrest (OHCA) with persistent coma after the return of spontaneous circulation (ROSC) were eligible. We excluded patients for whom OHCA was associated with traumatic brain injury, no possibility of TCD measurements, or who were dead before establishing the neurological prognosis. We measured the pulsatility index (PI) and diastolic flow velocity (DFV) of the right and left middle cerebral arteries within 12 h after ICU admission. The lowest DFV and highest PI values were used for the statistical analysis. The neurological outcome at hospital discharge was evaluated by the cerebral performance category. Results Forty-two patients were included in the final analysis: 15 had good and 27 poor neurological outcomes. The PI was higher in the poor outcome (1.49 vs. 1.12, p = 0.01) than good outcome group and the DFV was lower in the poor outcome group (17.3 cm s−1 vs. 26.0 cm s−1; p = 0.01). Conclusion Data provided by early TCD after ROSC are associated with neurological outcome. The use of TCD could help guide interventions to improve cerebral perfusion after ROSC in patients resuscitated from OHCA.

International audience; Procedures using iodine-131 represent more than 90% of all therapies in nuclear medicine in Algeria. It is important to evaluate the long-term biological effects of iodine treatment on non-target organs to improve patient radiation protection. This experimental radiotoxicology study aims to determine the biokinetic models of iodine contamination. For this purpose, two Wistar rat models, with and without a thyroid, have been used to evaluate the biological half-life of iodine and then to perform a biodistribution study of iodine activity in 15 organs and tissues. For the most relevant organs, the respective absorbed doses have been calculated using RODES software. © 2019 Society for Radiological Protection. Published on behalf of SRP by IOP Publishing Limited. All rights reserved.

Background: Although performed daily, intubation in intensive care units (ICU) remains a critical procedure with life-threatening adverse events. High-flow therapy by nasal cannulae (HFNC) is now widespread in the operating room and in the ICU, especially for preoxygenation before intubation in non-hypoxemic patients. However, no large randomized study has assessed its relevance in this population. Methods: The PROTRACH study is a randomized, multicenter open-labelled, controlled trial, including non-severely hypoxemic patients requiring intubation in medical or surgical ICU. Patients were randomly allocated to receive 4-minute preoxygenation delivered by HFNC or standard high-flow face mask (HFFM) before intubation. HFNC was maintained throughout the intubation procedure whereas HFFM was removed to perform laryngoscopy. The primary outcome was the lowest pulse oximetry throughout the intubation procedure. Secondary outcomes included drop in pulse oximetry, adverse events related to intubation, and outcome in the ICU. Main Findings: A total of 192 patients were randomized. In the intent-to-treat analysis, 184 patients (HFNC n = 95; HFFM n = 89), the median [IQR] lowest pulse oximetry was 100% [97;100] for HFNC and 99 % [95;100] for the HFFM group (P = 0.30). Mild desaturation below 95% was more frequent with HFFM (23%) than with HFNC (12%) (relative risk 0.51, CI 95% [0.26 to 0.99], P = 0.045). There were fewer adverse events in the HFNC group (6%) than in the HFFM group (19%) (relative risk 0.31, CI 95% [0.13 to 0.76], P = 0.007), including significantly fewer severe adverse events, respectively 6 (6%) and 14 (16%) with HFNC and HFFM (relative risk 0.38, CI 95% [0.15 to 0.95], P = 0.03). There was no difference in the outcome in the ICU with a mortality rate of 27% in both groups (P = 0.90). Interpretation: Compared with HFFM, preoxygenation with HFNC in the ICU did not improve the lowest level of pulse oximetry during intubation in the non-severely hypoxemic patients but led to a reduction in severe and moderate intubation-related adverse events. Clinical Trial Number: Clinicaltrials.gov identifier: NCT02700321, Eudra CT: 2015-A00145-44 Funding Statement: The French Ministry of Health (Interregional French Clinical Hospital Research Program grant (PHRCi 2014 - API12/N/077), a grant for research & innovation missions (University Hospital of Nantes) and by Fisher & Paykel Healthcare. Declaration of Interests: Declaration of Interest: Christelle Volteau, Gwenael Colin, Adel Maamar, Vanessa Jean Michel, Pierre Joachim Mahe, Mickael Landais, Noelle Brule, Cedric Bretonniere, Olivier Zambon and Christophe Guitton declare no conflict of interest. Stephan Ehrmann declares receiving consultancy fees from Aerogen Ltd, La Diffusion Technique Francaise and Baxter healthcare and unrestricted research support from Fisher and Paykel, Aerogen Ltd and Hamilton medical. Mickael Vourc’h declares personal fees from MSD, Pfizer, Baxter, grants from Fisher Paykel, outside the submitted work. Ethics Approval Statement: Three methods of consent were available. When possible, capable patients were included after written informed consent. Most patients were included after the written informed consent of their next-of-kin or following an emergency inclusion procedure if not available at the time of inclusion. Then, consent was obtained from all patients as soon as possible after recovery. The appropriate ethics committee (Comite de Protection des Personnes, Rennes, France) approved this study protocol in September 2015 (15/13-975).

Background Myocardial dysfunction is one of the mechanisms involved in the pathophysiology of septic shock. The role of troponin as a surrogate of myocardial injury in septic shock is still debated. The aim of this study was to assess the prognostic value of high-sensitivity cardiac troponin I (hs-cTnI) assay in predicting 28-day mortality in patients with septic shock. Materials and Methods Prospective study including 75 patients with septic shock admitted to a medico-surgical ICU from January to December 2017. Patients under the age of 18 years, known pregnancy and patients in post–cardiac arrest were excluded. Clinical and demographic data including age, gender, comorbidities, SAPS II and SOFA scores were collected. Hs-cTnI was measured soon after admission and 12, 24, 48 and 72 after. Receiver operating characteristic (ROC) analysis was performed to identify the most useful troponin I cut-off level for the prediction of 28-day mortality. A p

This study was performed to investigate the distribution of antimicrobial resistance genes and extra-intestinal virulence determinants in a collection of 98 Escherichia coli strains isolated from rectal swabs of healthy children. Forty-six isolated strains were resistant to at least one of the tested antibiotics (usually active against enterobacteria). They were mainly resistant to ampicillin and ticarcillin (42.97%), tetracyclin (26.5%), and trimethoprim/sulfamethoxazole (18.4%). No resistance to the third generation of cephalosporins, carbapenems, aminoglycosides and colistin was found. Resistance to penicillins was encoded by blaTEM-1 (n=34) and blaSHV-1 genes (n=4). Tetracyclin resistance was encoded by tetB (n=12), tetA (n= 5), and tetC (n=1) genes. Amongst resistant quinolones isolated (n=5), chromosomal mutations in gyrA and parC genes were detected in four isolates and qnrS1 gene in two strains. Nine plasmid replicon types were detected; IncFIB (n=36) and IncI1 (n=7) were the most frequent ones. Isolates frequently belonged to phylogenetic groups A (51.1%) and D (27.5%). Extra-intestinal pathovar (n=38) occurred mainly in B2 phylogroup (P=0.0002). Amongst them, two isolates (non-extended-spectrum-β-lactamase (ESBL)-producers) belonged to the pandemic clone ST131. A significant distribution of virulence determinants and pathogenicity island marker was observed within strains belonging to B2 and D phylogroups. Interestingly, our results showed that ExPEC strains, including ST131 pandemic clone, are present within fecal isolates in healthy children. These findings highlight the importance of intestinal microbiota as a reservoir for virulent and resistant strains. Thus, reinforcing hand hygiene and antibiotic rational use is imperative to avoid the diffusion of these pathogens in the community.

Gastrointestinal colonisation by carbapenem-resistant Acinetobacter baumannii (CRAB) is a critical step before nosocomial infection. This study evaluated CRAB intestinal carriage in patients admitted to a Tunisian ICU and determined the antimicrobial resistance mechanisms involved. From December 2014 to February 2015, all 63 patients admitted to the ICU were screened for rectal CRAB colonisation upon admission and once weekly thereafter. ICU patients who acquired a CRAB nosocomial infection were also included. β-Lactamases and associated resistance genes were screened by PCR sequencing, and molecular typing was performed by PFGE and MLST. The CRAB faecal carriage rate at admission was 4.8% (3/63). The CRAB acquisition rate during ICU stay was analysed in 39 of the remaining 60 patients and the rate of acquired CRAB faecal carriage was 15.4% (6/39); 4 patients also showed an ICU-acquired CRAB infection (one patient was a faecal carrier and suffered infection). Overall, 13 CRAB isolates were collected from 12 patients, of which 11 isolates showed resistance to all antibiotics tested except colistin. blaOXA-23 and blaNDM-1 were detected in 11 and 2 isolates, respectively. All OXA-23-producing strains carried armA, tetB, sul1 and catB, and some of them carried aph(3′)-VIa, blaTEM-1, aph(3′)-Ia and ant(2′′)-Ia. The blaNDM-1-positive isolates harboured aph(3′)-VIa and catB. Three PFGE patterns and two STs were identified [ST195 (n = 11), ST1089 (n = 2, NDM-1-positive)]. Whether imported or acquired during ICU stay, CRAB colonisation is a major risk factor for the occurrence of serious nosocomial infection. Systematic screening of faecal carriage is mandatory to prevent their spread.