Role of fluid status markers as risk factors for suboptimal vancomycin concentration during continuous infusion in neonates: an observational study.

Vancomycin is widely used in neonatal sepsis but proportion of newborn reaching recommended concentration is variable. Fluid status impact on vancomycin level remains understudied. We aimed to study fluid factors impacting vancomycin concentration at 24 h of treatment. We performed a prospective and retrospective observational monocentric study of NICU patients requiring a vancomycin treatment. We used a continuous infusion protocol, with age-appropriate loading and maintenance doses. Vancomycin target serum concentration after 24 h (C24h) was above 20 mg/L. Demographic, infections, and organ failure variables were analyzed as potential predictors of C24h. Over the study period, 70 infective episodes in 52 patients were included. At treatment initiation, the median post-natal age was 12.5 days (IQR 7-23), post menstrual age 30 weeks (IQR 28-35), and median weight 1140 g (IQR 835-1722). Germs isolated were mainly gram-positive with 73.5% being coagulase-negative Staphylococci. Median C24h was 18.7 mg/L (IQR 15.4-22.4). Overall, 41 (58.6%) treatments had a C24h < 20 mg/L. After multivariate analysis, higher creatinine level (OR 1.03 (95% CI 1.002-1.06)) was associated with C24h ≥ 20 mg/L; weight gain the day before infection (OR 0.21 (95% CI 0.05-0.79)) and positive biomarkers of inflammation (OR 0.22 (0.05-0.94)) were associated with C24h < 20 mg/L. CONCLUSION: Vancomycin C24h was underdosed in 60% of patients and factors linked to changes in vancomycin pharmacokinetic such as volume of distribution and clearance, linked to creatinine level, inflammation, or weight gain, were identified. WHAT IS KNOWN: • Adjustment of vancomycin regimen remains difficult due to inter- and intra-individual variability of vancomycin pharmacokinetics. • Impact of fluid status on vancomycin concentration in critically ill neonates is incompletely studied. WHAT IS NEW: • Proportion of patients with adequate vancomycin concentration using a target adapted to nosocomial gram-positive bacteria MIC is low. • We confirmed the role of creatinine level and report two new factors associated with low vancomycin concentration: presence of systemic inflammation and weight gain.

The First 2 Years of Activity of a Specialized Organ Procurement Center: Report of an Innovative Approach to Improve Organ Donation.

The number of patients requiring organ transplants continues to outgrow the number of organs donated each year. In an attempt to improve the organ donation process and increase the number of organs available, we created a specialized multidisciplinary team within a specialized organ procurement center (OPC) with dedicated intensive care unit (ICU) beds and operating rooms. The OPC was staffed with ICU nurses, operating room nurses, organ donor management ICU physicians, and multidisciplinary staff. All organ donors within a designated geographic area were transferred to and managed within the OPC. During the first 2 years of operation, 126 patients were referred to the OPC. The OPC was in use for a total of 3527 h and involved 253 health workers. We retrieved 173 kidneys, 95 lungs, 68 livers, 37 hearts, and 13 pancreases for a total of 386 organs offered for transplantation. This translates to a total of 124.6 persons transplanted per million population, which compares most favorably to recently published numbers in developed countries. The OPC clearly demonstrates potential to increase the number of deceased donor organs available for transplant. Further studies are warranted to better understand the exact influence of the different components of the OPC on organ procurement.

Characterization and phylogenetic analysis of new bat astroviruses detected in Gabon, Central Africa.

Astroviruses are emerging RNA viruses that cause enteropathogenic infections in humans and in other mammals. The identification of astroviruses in a wide range of animals highlights the zoonotic importance of these viruses. Bats can harbor many different viruses, among which some are highly pathogenic for humans (for instance, Nipah, Ebola and SARS coronavirus), and also several astroviruses. As some RNA viruses can be directly transmitted from bats to humans, it is crucial to collect data about their frequency, genetic diversity and phylogenetic characterization. In this study, we report the molecular identification of 44 new astroviruses (with a detection rate of 4.5%) in 962 apparently healthy bats that belong to five different species and that were captured in different caves in North-East Gabon, Central Africa. Our results show that bat astroviruses form a group that is genetically distinct from astroviruses infecting other mammals. Moreover, these astroviruses showed an important genetic diversity and low host restriction in bat species.

The dehydration mechanism of Na and K birnessites: a comprehensive multitechnique study.

The structural, spectroscopic and electronic properties of Na and K birnessites were investigated from ambient conditions (birA) to complete dehydration, and the involved mechanisms were scrutinized. Density Functional Theory (DFT) simulations were employed to derive structural models for lamellar A0.33MnO2·xH2O (A = Na+ or K+, x = 0 or 0.66), subsequently compared with the experimental results obtained for Na0.30MnO2·0.75H2O and K0.22MnO2·0.77H2O materials. Thermal analysis (TGA-DSC), X-ray diffraction (XRD), Fourier Transform Infrared (FTIR) spectroscopy, and Near Ambient Pressure X-ray Photoemission Spectroscopy (NAP-XPS) measurements were conducted for both birnessites. Dehydration under vacuum, annealing, or controlled relative humidity were considered. Results indicated that complete birnessite dehydration was a two-stage process. In the first stage, water removal from the interlayer of fully hydrated birnessite (birA) down to a molar H2O/A ratio of ∼2 (birB) led to the progressive shrinkage of the interlayer distance (3% for Na birnessite, 1% for K birnessite). In the second stage, water-free (birC) domains with a shorter interlayer distance (20% for Na birnessite, 10% for K birnessite) appeared and coexisted with birB domains. Then, birB was essentially transformed into birC when complete dehydration was achieved. The vibrational properties of birA were consistent with strong intermolecular interactions among water molecules, whereas partially dehydrated birnessite (birB) showed a distinct feature, with 3 (for Na-bir) and 2 (for K-bir) vibrations that were reproduced by DFT calculations for organized water into the interlayer (x = 0.66). The study also demonstrated that the electronic structure of Na birnessite depends on the interlayer water content. The external Na+ electronic level (Na 2p) was slightly destabilized (+0.3 eV binding energy) under near ambient conditions (birA) compared to drier conditions (birB and birC).

A benign psoas teratoma of the non-pelvic retroperitoneal space: A case report.

This case report is of a benign retroperitoneal teratoma which was adherent to the psoas muscle of a 53-year-old female cadaver with a history of metastatic bladder cancer as a cause of death. Teratomas possess derivatives of all three germ cell layers and are usually seen either in children or in the lower pelvic region of adults. The finding of this mass deep to the inferior pole of the kidney is quite unusual. Few studies mention a possible association between metastatic cancer and teratoma growth in extrapelvic locations. The following report is a detailed account of this unusual finding and a summary of the literature on growths of this kind.

Effective size of the hierarchically structured populations of the agent of malaria: a coalescent-based model.

Using the coalescence theory, we derived a simple expression for the asymptotic inbreeding effective population size of Plasmodium falciparum, the most malignant agent of malaria, in relationship to F-statistics at different hierarchical levels. We consider the effective size of malaria parasites, both for the intrinsic interest of the result for the study of this medically important organism and as an example illustrating general arguments that should clarify effective size calculations in a wide range of organisms with complex life cycles and a hierarchical population structure. We consider in this study a model with four hierarchical levels (villages, oocyst infrapopulations, oocysts within infrapopulations and the oocyst). The derived expression is applicable to both island and isolation by distance models and is a function of three F-statistics: the genetic differentiation among villages (F(VT)), the genetic differentiation among oocyst infrapopulations (F(MV)) and, finally, the departure from panmixia (F(IM)) within oocyst infrapopulations. The logic of the derivation of effective size presented in this study is applicable to any organism showing the same levels of subdivision.

Abdominal musculature segmentation and surface prediction from CT using deep learning for sarcopenia assessment.

PURPOSE: The purpose of this study was to build and train a deep convolutional neural networks (CNN) algorithm to segment muscular body mass (MBM) to predict muscular surface from a two-dimensional axial computed tomography (CT) slice through L3 vertebra. MATERIALS AND METHODS: An ensemble of 15 deep learning models with a two-dimensional U-net architecture with a 4-level depth and 18 initial filters were trained to segment MBM. The muscular surface values were computed from the predicted masks and corrected with the algorithm's estimated bias. Resulting mask prediction and surface prediction were assessed using Dice similarity coefficient (DSC) and root mean squared error (RMSE) scores respectively using ground truth masks as standards of reference. RESULTS: A total of 1025 individual CT slices were used for training and validation and 500 additional axial CT slices were used for testing. The obtained mean DSC and RMSE on the test set were 0.97 and 3.7 cm2 respectively. CONCLUSION: Deep learning methods using convolutional neural networks algorithm enable a robust and automated extraction of CT derived MBM for sarcopenia assessment, which could be implemented in a clinical workflow.

[French 2008 guidelines on peritoneal dialysis: indications and non-indications]. / Indications et non-indications de la dialyse péritonéale chronique chez l'adulte. Recommandations françaises en 2008.

The new French guidelines on Peritoneal Dialysis (PD) were published in october 2008 by the "Haute Autorité de Santé (HAS)". The field of these guidelines concerned the choice between PD and Hemodialysis (HD), on a strict medical point of view. This paper summarizes the main French PD guidelines, highlighting the new insights compared to previous guidelines. For the first time, guidelines described 5 clinical situations requiring the choice between PD or HD : 1) criteria for choosing PD in a new dialysis patient ; 2) criteria for switching a patient from PD to HD ; 3) criteria for switching a patient from HD to PD ; 4) PD or HD before kidney transplantation ; 5) PD or HD after graft failure. For a new dialysis patient, PD is recommended, more than HD, for cirrhotic patients with ascites, kidney failure due to cholesterol embolism, difficulties for HD-vascular access. PD is not recommended in only a few cases : morbid obesity (BMI>45 kg /m(2)), irreparable abdominal hernias. It is recommended to switch from PD to HD, patients with more than 3 peritonitis/year, due to digestive bacteria ; weight gain > 15 % per year ; triglycerid serum level > 10 g/l ; loss of peritoneal efficiency. It is recommended to switch from HD to PD patients with vascular access failure ; hemodynamic instability during HD sessions ; severe congestive heart failure. PD or HD can be indistinctly used before kidney or combined pancreas-kidney graft. These new French guidelines are more complete and more accurate than the previous French or international guidelines.

[Glassy cell carcinoma of the uterine cervix: An aggressive type of cancer]. / Glassy cell carcinoma du col de l'utérus : une maladie tumorale agressive.

INTRODUCTION: Cervical cancer is the twelfth most frequent cancer in women in France. Glassy cell carcinoma is a rare histological entity, rapidly aggressive, associated with a poor prognosis. CASE REPORT: A 30-year-old woman was admitted in an internal medicine department for polyarthralgia with high grade fever, evolving for 3 weeks. There was an inflammatory syndrome. The 18-FDG-PET-scan showed inflammatory lymph nodes as well as disseminated osteolytic lesions, and a primitive pelvic tumor. A 3cm tumor of the cervix was found during the gynaecologic examination. Histological analysis elicited a high-index mitotic carcinoma, glassy cell carcinoma type. Despite chemotherapy, the outcome was poor, with early death occurring after three months of follow-up. CONCLUSION: The glassy cell carcinoma of the cervix should be considered as an aetiology of bone metastases in young female patients.

Field comparison of disjunct and conventional eddy covariance techniques for trace gas flux measurements.

A field intercomparison experiment of the disjunct eddy covariance (DEC) and the conventional eddy covariance (EC) techniques was conducted over a grass field. The half-hourly water vapor fluxes measured by the DEC were within the estimated uncertainty from the fluxes measured by the EC. On the average there was a slight overestimation (<10%) of the fluxes measured by the DEC during the day and underestimation during the night as compared to the fluxes measured by the EC. As this bias does not appear in the simulated DEC measurements it is likely to be due to instrumental problems. The insensitivity of the quality of the fluxes measured by the DEC method to the deficiencies in the gas analysis shows the robustness of this new approach for measuring the surface-atmosphere exchange of trace gases.

[A case of fatal cocaine overdose]. / Intoxication mortelle à la cocaïne.

Clinical, biological, and therapeutic description of a lethal case of cocaine overdose.

[Can a simple lung ultrasound score predict length of ventilation for infants with severe acute viral bronchiolitis?] / Un score échographique pulmonaire simple peut-il prédire la durée de ventilation des nourrissons atteints de bronchiolite aiguë sévère ?

BACKGROUND: Lung ultrasound (LU) is a bedside point-of-care technique in critical care and emergency medicine. LU is quick and non-irradiating, and provides accurate diagnostic information when compared with chest radiographs. Specific LU signs have been described for bronchiolitis. This study aimed to evaluate the correlation between severity of LU-diagnosed lung lesions, using a quantitative LU score, and the length of non-invasive ventilation (LOV) for infants diagnosed with severe viral bronchiolitis. METHODS: This was a prospective observational single-center study conducted at a level 3 pediatric intensive care unit. A LU score was calculated for 47 infants under 6 months of age with severe acute viral bronchiolitis during the 2015-2016 epidemic, and the number of intercostal spaces with consolidation or interstitial syndrome was counted for each lung. The LU score is based on the presence of A lines or B-line artifacts and consolidation (0-2 points). The modified Wood score (mWCAS) was used to define clinical severity. Other parameters such as gestational age at birth, age, supplemental oxygen (LOS), and length of stay were recorded. All LU scans were later reviewed by two trained ultrasonographers to assess the score's inter-rater reproducibility. RESULTS: The LU score on admission (3.5±2.6) did not correlate with LOV (69±68.6), mWCAS score (4±1.6), LOS (3±3.4), or length of stay (4±3.4). However, there was a significant correlation between the number of affected intercostal spaces on the right and LOS (Spearman's Rho 0.318; P=0.037). CONCLUSION: This is the first study to evaluate the use of LU in infants needing PICU admission for severe acute bronchiolitis. The LU score does not correlate with LOV, mWCAS, LOS, or length of stay, but the number of pathological intercostal spaces on the right side correlates significantly with LOS. Although LU scores have been validated for the newborn and the adult, this has been in the setting of restrictive lung diseases. Bronchiolitis is a predominantly obstructive lung disease and this may explain the lack of performance observed.

Inactivation of the IGF-I receptor gene in primary Sertoli cells highlights the autocrine effects of IGF-I.

IGF-I regulates pituitary and gonadal functions, and is pivotal for sexual development and fertility in mammalian species. To better understand the function of autocrine IGF-I in Sertoli cell physiology, we established a system for Cre-mediated conditional inactivation of the IGF-I receptor (IGF-IR) in cultured Sertoli cells. We show here that loss of IGF-IR decreased the number of viable Sertoli cells as a consequence of diminished Sertoli cell proliferation and increased Sertoli cell death. Furthermore, the lack of IGF-IR altered the morphology of cultured Sertoli cells and decreased lactate and transferrin secretions. Collectively, our data indicate that autocrine IGF-I contributes significantly to Sertoli cell homeostasis. The described in vitro system for loss-of-function analysis of the IGF-IR can be readily transposed to study the role of other intratesticular growth factors involved in spermatogenesis.

15N-Nitrate signature in low-order streams: effects of land cover and agricultural practices.

Many studies have shown that intensive agricultural practices significantly increase the nitrogen concentration of stream surface waters, but it remains difficult to identify, quantify, and differentiate between terrestrial and in-stream sources or sinks of nitrogen, and rates of transformation. In this study we used the delta15N-NO3 signature in a watershed dominated by agriculture as an integrating marker to trace (1) the effects of the land cover and agricultural practices on stream-water N concentration in the upstream area of the hydrographic network, (2) influence of the in-stream processes on the NO3-N loads at the reach scale (100 m and 1000 m long), and (3) changes in delta15N-NO3 signature with increasing stream order (from first to third order). This study suggests that land cover and fertilization practices were the major determinants of delta15N-NO3 signature in first-order streams. NO3-N loads and delta15N-NO3 signature increased with fertilization intensity. Small changes in delta15N-NO3 signature and minor inputs of groundwater were observed along both types of reaches, suggesting the NO3-N load was slightly influenced by in-stream processes. The variability of NO3-N concentrations and delta15N signature decreased with increasing stream order, and the delta15N signature was positively correlated with watershed areas devoted to crops, supporting a dominant effect of agriculture compared to the effect of in-stream N processing. Consequently, land cover and fertilization practices are integrated in the natural isotopic signal at the third-order stream scale. The GIS analysis of the land cover coupled with natural-abundance isotope signature (delta15N) represents a potential tool to evaluate the effects of agricultural practices in rural catchments and the consequences of future changes in management policies at the regional scale.

Evolution of DNA strand-breaks in cultured spermatocytes: the Comet Assay reveals differences in normal and gamma-irradiated germ cells.

In reproductive toxicity assessment, in vitro systems can be used to determine mechanisms of action of toxicants. However, they generally investigate the immediate effects of toxicants, on isolated germ cells or spermatozoa. We report here the usefulness of in vitro cultures of rat spermatocytes and Sertoli cells, in conjunction with the Comet Assay to analyze the evolution of DNA strand-breaks and thus to determine DNA damage in germ cells. We compared cultures of normal and gamma-irradiated germ cells. In non-irradiated spermatocytes, the Comet Assay revealed the presence of DNA strand-breaks, which numbers decreased with the duration of the culture, suggesting the involvement of DNA repair mechanisms related to the meiotic recombination. In irradiated cells, the evolution of DNA strand-breaks was strongly modified. Thus our model is able to detect genotoxic lesions and/or DNA repair impairment in cultured spermatocytes. We propose this model as an in vitro tool for the study of genotoxic injuries on spermatocytes.

Quality improvement program of adult urinary tract infection management: Review and impact.

OBJECTIVE: A quality improvement program for adult urinary tract infection management was established to avoid unnecessary antibiotic treatment and to promote adequate prescription, associated with financial and time savings. METHODS: Management was integrated into a three-step approach: clinical diagnosis, bacteriological diagnosis, and therapeutic decision. For each step, areas for improvement were prioritized and implemented through corrective measures and key messages, measured by indicators. This program was applied to the whole hospital, which includes an emergency department and hospital units (672 beds). RESULTS: The diffusion of new recommendations on clinical diagnosis helped limit the use of Urine Dipstick Tests (UDT) and identify situations requiring the prescription of urine cytobacteriological test (UCBE) and antibiotic treatment: decreased annual consumption of UDTs (34%) and UCBEs (25%). The implementation of a new sampling system for UCBEs was associated with a 21% increase in conclusive analysis. Results of antimicrobial susceptibility testing were also optimized. Trainings on the proper use of antibiotics led to a 5.0% decline in global consumption. Only 23 antibiotic prescriptions for UTI resulted in pharmaceutical advice to prescribers in 2014. CONCLUSION: The program is part of a practice improvement strategy. Integrating the management of urinary tract infections into a global process helped improve each step of patient management.

Molecular divergences of the Ornithodoros sonrai soft tick species, a vector of human relapsing fever in West Africa.

The soft tick Ornithodoros sonrai is recognized as the only vector of Borrelia crocidurae causing human relapsing fever in West Africa. Its determination has been exclusively based on morphological features, geographical distribution and vector competence. Some ambiguities persist in its systematics and may cause misunderstanding about West African human relapsing fevers epidemiology. By amplifying and aligning 16S and 18S rDNA genes in O. sonrai specimens collected from 14 distinct sites in Senegal and Mauritania, we showed the existence of four genetically different subgroups that were morphologically and ecologically identified as belonging to the same species. Within O. sonrai, intraspecific polymorphism was high (pairwise divergence from 0.2% to 16.4%). In all cases, these four subgroups formed a monophyletic clade sharing a common ancestor with East African soft ticks that transmit Borrelia duttoni human relapsing fever. From amplification of the flagellin gene of B. crocidurae we verified that all subgroups of O. sonrai were infected by B. crocidurae and may constitute vectors for this pathogen. All flagellin sequences were identical, refuting the hypothesis suggesting parallel evolution between O. sonrai and B. crocidurae. However, differences in infection rates were significant, suggesting different vector competences between subgroups of O. sonrai.

[Effects of nasal continuous positive airway pressure ventilation in infants with severe acute bronchiolitis]. / Place de la ventilation non invasive nasale dans la prise en charge des broncho-alvéolites sévères.

OBJECTIVE: Usefulness of nasal continuous positive airway pressure (NCPAP) in severe acute bronchiolitis has been checked. The objective of this descriptive study was to evaluate the feasibility, safety and risk factors of NCPAP failure. POPULATION AND METHODS: One hundred and forty-five infants were hospitalised in our intensive care unit during the 2 last epidemics (2003-2004, 2004-2005). Among them, 121 needed a respiratory support, either invasive ventilation (N=68) or NCPAP (N=53). RESULTS: General characteristics were similar during the 2 periods. Percentage of NCPAP failure, defined by tracheal intubation requirement during the stay in paediatric intensive care unit, was quite similar during the 2 periods (25%), but number of NCPAP increased twofold. Whatever the evolution was in the NCPAP group, we observed a significant decrease in respiratory rate (60+/-16 vs 47.5+/-13.7 cycle/min., P<0.001) and PaCO2 (64.3+/-13.8 vs 52.6+/-11.7 mmHg, P=0.001) during NCPAP. Only PRISM calculated at day 1 and initial reduction of PaCO2 were predictive of NCPAP failure. Percentage of ventilator associated pneumonia was similar (22%) between the invasive ventilation group and infants who where intubated because of failure of NCPAP. Duration of respiratory support and stay were reduced in the NCPAP group (P<0.002). CONCLUSION: NCPAP appears to be a safe alternative to immediate intubation in infants with severe bronchiolitis.

Glucocorticoid enhancement of glucocorticoid production by cultured ovine adrenocortical cells.

The present study examines the effect of chronic treatment with glucocorticoids on the steroidogenic activity of ovine adrenocortical cells in vitro. Cells cultured in the presence of 10(-9) to 10(-5) M dexamethasone produced more glucocorticosteroids in response to ACTH1-24, forskolin or 8 BrcAMP than did control cells. Such an enhancing effect required more than 5 h of treatment and was maximal at 30 h; it was both concentration-dependent and steroid-specific. The maximal secretion of corticosteroids was observed when cells were exposed to 10(-7) M dexamethasone; with higher concentrations the response to ACTH1-24 decreased steadily; the ED50 was 2.8 +/- 0.8 nM. Cortisol and corticosterone enhanced ACTH1-24-induced steroidogenesis to the same extent as dexamethasone, but at concentrations roughly 100-fold higher than for dexamethasone. Testosterone and 17 beta-oestradiol had no enhancing effect. Dexamethasone not only enhanced the maximal steroidogenic response to ACTH1-24 but also decreased its ED50 3-fold. Treatment of cultures with the antiglucocorticoid RU 38486 resulted in a dose-dependent, time-dependent, decrease in ACTH1-24-induced corticosteroid output. Moreover, RU 38486 antagonized the enhancing effect of dexamethasone. The production of corticosteroids by dexamethasone-treated cells incubated in the presence of 22(R)-hydroxycholesterol or of exogenous pregnenolone was similar to that of control cells. The enhancing effect of dexamethasone was also observed when cultures were performed in the absence of insulin and/or in serum-free media. These data suggest that chronic exposure to glucocorticoids is necessary for the full steroidogenic activity of ovine adrenocortical cells. Moreover, they indicate that glucocorticoids exert their effect at least at two different levels in the cell: (i) on the adenylate cyclase system and (ii) at step(s) beyond cAMP but before pregnenolone formation.