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Purpose: Although patients with SARS-CoV-2 infection have several risk factors for ventilator-associated lower respiratory tract infections (VA-LRTI), the reported incidence of hospital-acquired infections is low. We aimed to determine the relationship between SARS-CoV-2 pneumonia, as compared to influenza pneumonia or no viral infection, and the incidence of VA-LRTI. Methods: Multicenter retrospective European cohort performed in 36 ICUs. All adult patients receiving invasive mechanical ventilation > 48 h were eligible if they had: SARS-CoV-2 pneumonia, influenza pneumonia, or no viral infection at ICU admission. VA-LRTI, including ventilator-associated tracheobronchitis (VAT) and ventilator-associated pneumonia (VAP), were diagnosed using clinical, radiological and quantitative microbiological criteria. All VA-LRTI were prospectively identified, and chest-X rays were analyzed by at least two physicians. Cumulative incidence of first episodes of VA-LRTI was estimated using the Kalbfleisch and Prentice method, and compared using Fine-and Gray models. Results: 1576 patients were included (568 in SARS-CoV-2, 482 in influenza, and 526 in no viral infection groups). VA-LRTI incidence was significantly higher in SARS-CoV-2 patients (287, 50.5%), as compared to influenza patients (146, 30.3%, adjusted sub hazard ratio (sHR) 1.60 (95% confidence interval (CI) 1.26 to 2.04)) or patients with no viral infection (133, 25.3%, adjusted sHR 1.7 (95% CI 1.2 to 2.39)). Gram-negative bacilli were responsible for a large proportion (82% to 89.7%) of VA-LRTI, mainly Pseudomonas aeruginosa, Enterobacter spp., and Klebsiella spp. Conclusions: The incidence of VA-LRTI is significantly higher in patients with SARS-CoV-2 infection, as compared to patients with influenza pneumonia, or no viral infection after statistical adjustment, but residual confounding may still play a role in the effect estimates. © 2021, Springer-Verlag GmbH Germany, part of Springer Nature.

During limb development, the spatio-temporal expression of sonic hedgehog (SHH) is driven by the Zone of polarizing activity Regulatory Sequence (ZRS), located 1 megabase upstream from SHH. Gain-of-function mutations of this enhancer, which cause ectopic expression of SHH, are known to be responsible for congenital limb malformations with variable expressivity, ranging from preaxial polydactyly or triphalangeal thumbs to polysyndactyly, which may also be associated with mesomelic deficiency. In this report, we describe a patient affected with mirror-image polydactyly of the four extremities and bilateral tibial deficiency. The proband's father had isolated preaxial polydactyly type II (PPD2). Using Sanger sequencing, a ZRS point mutation (NC_000007.14, g.156584153A>G, UCSC, Build hg.19) was only identified in the patient. However, pyrosequencing analysis enabled the detection of a 10% somatic mosaic in the blood and saliva from the father. To our knowledge, this is the first description of a ZRS mosaic mutation. This report highlights the complexity of genotype-phenotype correlation in ZRS-associated syndromes and the importance of detecting somatic mosaicism for accurate genetic counselling.

Objectives The study objectives were to describe the investigation and management of an imipenem-resistant Acinetobacter baumannii outbreak that occurred in the 15-bed ICU of a tertiary care teaching hospital (Brest, France), during the summer 2008. Patients and methods Patients harboring an imipenem-resistant A. baumannii strain were defined as case patients. We described case occurrence and steps taken to control the outbreak: contact isolation, reinforcement of hygiene procedures, unit shutdown decision, unit disinfection, and reopening. We also made a case control study and a cost analysis of the outbreak management. Results During a 10-day period, five patients were positive for a single clone of imipenem-resistant oxa-23 A. baumannii. Four patients presented with ventilation-acquired pneumonia and one was asymptomatic. The first two patients died one day after the first swab which led to the identification of A. baumannii. No additional case was noted in the ICU or in other hospital units after deciding to close the ICU. The cost of outbreak management was estimated at 264,553 euros. The case control study identified several factors associated with infection or colonization: length of stay in the ICU, chronic respiratory disease, number of previous antibiotic classes used, duration of ventilation, prone position, echocardiography, and presence of a nasogastric tube. Conclusion This outbreak occurred during the summer period requiring the shutdown of the ICU and inducing a considerable cost. Rapid reactions of the ICU staff during the outbreak enabled to limit the epidemic.

From September to December 2004, contaminations were found in fifteen conservation and transport mediums of corneal grafts at the tissue bank of Brest, including seven by Sphingomonas paucimobilis. The pulsed-field gel electrophoresis made it possible to establish the genotypic profiles of each strain and to compare them. Similarities were found between certain strains of the contaminated mediums and those of the thermostated double boiler of the tissue bank. The link between the contamination and the defrosting of the mediums in the double boiler was thus established. Measures of prevention are currently proposed to defrost the bottles like the use of a dry bath to replace the current one.

Previous results from our laboratory have shown that 17beta-oestradiol prevents 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) striatal dopamine depletion. 17beta-oestradiol, oestriol and oestrone are the naturally occurring oestogens in humans. Using various dopamine markers, the present study investigated whether oestrone and oestriol such as 17beta-oestradiol have neuroprotective activity in MPTP-treated mice. Male mice were treated with 17beta-oestradiol, oestriol or oestrone for 5 days before and after MPTP administration, and were compared with nonlesioned mice receiving the same treatment. Striatal concentrations of dopamine and its metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), were assayed by high-performance liquid chromatography. Dopamine transporter (DAT) and vesicular monoamine transporter (VMAT2) specific binding were measured by autoradiography. DAT, VMAT2 and tyrosine hydroxylase mRNA levels were measured by in situ hybridisation. MPTP induced a loss of DAT and VMAT2 specific binding in the striatum and substantia nigra, as well as a decrease of VMAT2 mRNA in the substantia nigra. 17beta-oestradiol treatment prevented the loss of these dopaminergic markers, as well as striatal concentrations of dopamine, DOPAC and HVA. Mice receiving oestriol and oestrone showed catecholamine concentrations comparable to MPTP mice. Oestriol treatment had no effect on dopaminergic markers in MPTP mice whereas oestrone prevented striatal DAT loss and the decrease of VMAT2 mRNA in the substantia nigra. In nonlesioned mice, 17beta-oestradiol, oestriol or oestrone had no effect on all the dopaminergic markers investigated. In conclusion, a weak or a lack of effect of oestriol and oestrone was observed compared to 17beta-oestradiol in MPTP mice and none of these steroids had an effect in nonlesioned mice. A DAT and VMAT2 specific binding decrease after MPTP in the striatum and substantia nigra, as well as a decrease of substantia nigra VMAT2 mRNA, was observed and could be prevented by oestradiol.

During limb development, the spatio-temporal expression of sonic hedgehog (SHH) is driven by the Zone of polarizing activity Regulatory Sequence (ZRS), located 1 megabase upstream from SHH. Gain-of-function mutations of this enhancer, which cause ectopic expression of SHH, are known to be responsible for congenital limb malformations with variable expressivity, ranging from preaxial polydactyly or triphalangeal thumbs to polysyndactyly, which may also be associated with mesomelic deficiency. In this report, we describe a patient affected with mirror-image polydactyly of the four extremities and bilateral tibial deficiency. The proband's father had isolated preaxial polydactyly type II (PPD2). Using Sanger sequencing, a ZRS point mutation (NC_000007.14, g.156584153AG, UCSC, Build hg.19) was only identified in the patient. However, pyrosequencing analysis enabled the detection of a 10% somatic mosaic in the blood and saliva from the father. To our knowledge, this is the first description of a ZRS mosaic mutation. This report highlights the complexity of genotype-phenotype correlation in ZRS-associated syndromes and the importance of detecting somatic mosaicism for accurate genetic counselling.

A method of semi-automated classification of windstorms over France is proposed, in order to provide insurance companies with meteorological statistical values, that could lead to an evaluation of storm risks. Because not all storm events have the same origins or the same features, and do not always hit the same regions, a classification is necessary in order to assemble storm events with meteorological and geographical similarities. The classification is based on the expert knowledge of a weather forecaster, who first analyses 44 storm events and draws out the meteorological features of different types of storm. Afterwards, the results of the human typology are automated by determining decisive rules with criteria, which are calculated with only observed meteorological surface data over France. The automation of the human typology is obtained by taking into account the main results of statistical methods such as objective classification or discrimination and by validating them with physical considerations. We thus succeed in formulating the reasoning of the expert. The classification is then applied to the Meteo-France records since 1962. We succeed in selecting 524 storm events and in classing them into seven main types, with enough events in each class to calculate statistical values. © 1998 Royal Meteorological Society

Nager syndrome belongs to the group of acrofacial dysostosis, which are characterized by the association of craniofacial and limb malformations. Recently, exome sequencing studies identified the SF3B4 gene as the cause of this condition in most patients. SF3B4 encodes a highly conserved protein implicated in mRNA splicing and bone morphogenic protein (BMP) signaling. We performed SF3B4 sequencing in 14 families (18 patients) whose features were suggestive of Nager syndrome and found nine mutations predicted to result in loss-of-function. SF3B4 is the major gene responsible for autosomal dominant Nager syndrome. All mutations reported predict null alleles, therefore precluding genotype-phenotype correlations. Most mutation-negative patients were phenotypically indistinguishable from patients with mutations, suggesting genetic heterogeneity.

Split hand/foot malformation (SHFM) with long-bone deficiency (SHFLD, MIM#119100) is a rare condition characterized by SHFM associated with long-bone malformation usually involving the tibia. Previous published data reported several unrelated patients with 17p13.3 duplication and SHFLD. Recently, the minimal critical region had been reduced, suggesting that BHLHA9 copy number gains are associated with this limb defect. Here, we report on 13 new families presenting with ectrodactyly and harboring a BHLHA9 duplication.

Introduction We had for aim to describe control and investigation of an outbreak caused by a strain of Extended spectrum beta-lactamase producing Klebsiella pneumoniae in intensive care units of the Brest teaching hospital. Patients and method The case definition was a patient infected by or carrying the epidemic strain. Control measures and investigations are presented. A case-control study was conducted in the surgical intensive care unit. Each case was matched with two controls based on admission times in the unit. The study focused on diagnostic and therapeutic procedures, and potential contacts with healthcare workers, in this context of cross transmission. Results Between February and May 2011, nine cases were reported in the surgical ICU and two in the medical ICU. Eighteen controls were matched with the nine surgical ICU cases. Several factors were found to be statistically associated with infection or colonization by the epidemic strain: the surgical block in which patients had been operated and the ward of first hospitalization; the number of trans-esophageal and trans-thoracic echocardiographies, of central venous catheter insertions, and of surgical operations; intubation. The total number of invasive procedures was also found to be statistically higher among cases. Conclusion This study identified factors associated with colonization or infection by the epidemic strain. These factors might have been involved in the transmission tree, and be vulnerable elements for the prevention of nosocomial infections and colonisations, and their epidemic spread.

International audience

Clinical and experimental studies show a modulatory role of estrogens in the brain and suggest their beneficial action in mental and neurodegenerative diseases. The estrogen receptors ERα and ERβ are present in the brain and their targeting could bring selectivity and reduced risk of cancer. Implication of ERs in the effect of estradiol on dopamine, opiate and glutamate neurotransmission is reviewed. The ERα agonist, PPT, is shown as estradiol to modulate hippocampal NMDA receptors and AMPA receptors in cortex and striatum of ovariectomized rats whereas the ERβ agonist DPN is inactive. Striatal DPN activity suggests implication of ERβ in estradiol modulation of D2 receptors and transporters in ovariectomized rats and is supported by the lack of effect of estradiol in ERβ knockout (ERKOβ) mice. Both ERα and ERβ agonists modulate striatal preproenkephalin (PPE) gene expression in ovariectomized rats. In male mice PPT protects against MPTP toxicity to striatal dopamine; this implicates Akt/GSK3β signaling and the apoptotic regulators Bcl2 and Bad. This suggests a role for ERα in striatal dopamine neuroprotection. ERKOα mice are more susceptible to MPTP toxicity and not protected by estradiol; differences in ERKOβ mice are subtler. These results suggest therapeutic potential for the brain of ER specific agonists. © 2007 Elsevier Ltd. All rights reserved.

From September to December 2004, contaminations were found in fifteen conservation and transport mediums of corneal grafts at the tissue bank of Brest, including seven by Sphingomonas paucimobilis. The pulsed-field gel electrophoresis made it possible to establish the genotypic profiles of each strain and to compare them. Similarities were found between certain strains of the contaminated mediums and those of the thermostated double boiler of the tissue bank. The link between the contamination and the defrosting of the mediums in the double boiler was thus established. Measures of prevention are currently proposed to defrost the bottles like the use of a dry bath to replace the current one.

Laparoscopic cholecystectomy for acute cholecystitis in the elderly remains a subject almost unstudied. A first study performed at Brugmann hospital broached the subject, but was rather unsatisfying. In fact, it showed that, except for a shorter hospital stay, laparoscopic cholecystectomy didn't have any advantages over open cholecystectomy. In view of the perfection in surgical technique and of the rapidity of management, we have analyzed our new results and compared them to the ones of our former study.In this current study we included patients aged over 75 years and with histologically proven acute cholecystitis. As such, we retrospectively studied 20 patients undergoing cholecystectomy from 1997 to 2002. Sixteen patients (80%) underwent laparoscopic cholecystectomy whereas 4 (20%) were considered unable to withstand the laparoscopic approach because of hemodynamic instability, they underwent open cholecystectomy.Age, APACHE-II scoring, white blood cell counts and CRP were more important in the laparotomy group, but there was no difference in terms of local and general complication or mortality rates between the two groups.Comparing the results with those of the first study (1991-1997), we established that the laparoscopic approach is very well indicated in the geriatric population. Also, the laparoscopy has been applied more appropriately, seen that our conversion rate dropped to zero. Still, open cholecystectomy proves to be indicated in critically ill patients.

Thirty patients presenting with post-dural puncture headache (PDPH) were prospectively studied to determine the influence of the duration of the decubitus position after epidural blood patch on the efficacy of treatment. All patients received 12 ml of autologous blood. They were randomly distributed into three groups of ten patients. Patients in Group 1 were maintained in a decubitus position for 30 min after the epidural injection of autologous blood in the epidural space. Patients in Group 2 were maintained for 60 min in decubitus and patients in Group 3 for 120 min. Post-dural puncture headache was evaluated using a visual analogue scale before the epidural blood patch, at the time of initially adopting a standing position after the blood patch, and 24 hr later. The severity of PDPH in the three groups was reduced at the time of initially adopting a standing position and after 24 hr, in comparison with pre-blood patch VAS (P < 0.001). Patients in Group 3 presented less severe PDPH than patients in Group 1 at the time of initially standing up and 24 hr later (P < 0.05). We conclude that epidural blood patch was effective in treating PDPH but that the maintenance of a decubitus position for at least one hour and preferably for two hours after the blood patch was more effective than maintenance for 30 min.

In order to evaluate the accuracy of a new infrared tympanic thermometer (ITT) TH 700 Rowenta or Thermo Sense CALOR for core temperature monitoring, rectal (Tre) and infrared tympanic temperature (Tty) have been recorded in all present inpatients of a general hospital, in 91.7% of patients, consistent results in Tty vs. Tre could be obtained (temperature range: 35.5 to 39.7/spl deg/C). When both right and left ears were explored, and then the highest value of Tty (TtyMax) was retained for records, no significant difference was found between mean (/spl plusmn/S.E.) Tre (36.83/spl plusmn/0.05/spl deg/C) and TtyMax (36.78/spl plusmn/0.05), Detection of maximal Tty was greatly facilitated by the outward orientation of the display screen and the possibility of making several readings within a few seconds while orientating the device into the best position for alignment with the tympanic membrane. Overall correspondence between Tes and Tty as recorded by TH 700 Rowenta or Thermo Sense Color was therefore found suitable for using this ITT in everyday clinical monitoring of core temperature.

International audience; Environmental influences on carbon isotope fractionation in tree rings require further elucidation in order to use this parameter as a biological marker of climatic variations. δ13C values in tree-ring cellulose of beech (Fagus sylvatica L.) were analysed for the period from 1950 to 1990. A bioclimatic model of water balance was used to give the actual evapotranspiration as well as the soil water content on a daily basis. δ13C shows a significant decrease from –24·5‰ to –25‰ over this period. Internal CO2 concentration changes from 200 to 220 ppm in relation with the rise of atmospheric CO2. Beside a slight non-significant inter-individual variation, a large year-to-year variation exists. The relative extractable soil water of July, combined with the value of δ13C for the previous year, predicts as much as 70% of this variance. Air temperature or precipitation accounted for less variation. δ13C is strongly correlated with basal area increment, but appeared a more reliable indicator of water status at the stand level.

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