Background: Severe COVID-19 is associated with exaggerated complement activation. We assessed the efficacy and safety of avdoralimab (an anti-C5aR1 mAb) in severe COVID-19. Methods: FORCE was a double-blind, placebo-controlled study. Patients receiving oxygen support ≥5 L/min to maintain SpO2 > 93% (WHO scale ≥ 5) were randomly assigned, in a 1:1 ratio to the avdoralimab and placebo arms. Avdoralimab (500 mg loading dose followed by a 200 mg maintenance dose) or placebo (normal saline) was administered intravenously every 48 h until oxygen therapy was no longer needed, and for a maximum of 14 days. Patients received conventional oxygen therapy or high-flow oxygen (HFO)/non-invasive ventilation (NIV) in cohort 1; HFO, NIV or invasive mechanical ventilation (IMV) in cohort 2 and IMV in cohort 3. The primary outcome was clinical status on the WHO ordinal scale at days 14 and 28 for cohorts 1 and 3, and the number of ventilator-free days at day 28 (VFD28) for cohort 2. Findings: Between May 2020 and January 2021, we randomized 207 patients: 99 in cohort 1, 49 in cohort 2 and 59 in cohort 3. Glucocorticoids were administered to 95% of patients during hospitalization. Avdoralimab did not improve WHO clinical scale score on days 14 and 28 (between-group difference on day 28 of -0.26 (95% CI, -1.2 to 0.7, p =0.7) in cohort 1 and -0.28 (95% CI, -1.8 to 1.2, p =0.6) in cohort 3). Avdoralimab did not improve VFD28 in cohort 2 (between-group difference of -6.3 (95% CI, -13.2 to 0.7, p =0.96), or secondary outcomes in any cohort. No subgroup of interest was identified. Interpretation: In this randomized trial in hospitalized patients with severe COVID-19 pneumonia, avdoralimab did not significantly improve clinical status at days 14 or 28. Trial Registration Details: This trial was registered with ClinicalTrials.gov, NCT04371367. Funding Information: Innate Pharma. Declaration of Interests: JK, SC, ABC, EV, JV, LB, OD, and others in the FORCE Study group are Innate Pharma employees and might hold stock. All other authors declare no competing interests. Ethics Approval Statement: The trial protocol was approved by the French National Agency for the Safety of Medicines and Health Products (ANSM, MEDAECNAT-2020-04-00043_2020-001686-36), and the competent ethics committee (Comité de Protection des Personnes Ouest II CPP #2020/34/Covid-19, EudraCT2020- 26 001686-36), and was overseen by an independent data and safety monitoring board (DSMB). Data were analyzed by independent statisticians at the International Drug Development Institute (IDDI). Written informed consent was obtained from all patients or their legal representatives (if the patient was unable to provide consent).

OBJECTIVES:. To determine the effect of the awake prone position (APP) on gas exchange and the work of breathing in spontaneously breathing patients with COVID-19–associated acute hypoxemic respiratory failure (AHRF) supported by high-flow nasal oxygen. DESIGN:. Prospective randomized physiologic crossover multicenter trial. SETTINGS:. Four ICUs in Marseille, France. PATIENTS:. Seventeen patients with laboratory-confirmed COVID-19 pneumonia and Pao2/Fio2 less than or equal to 300 mm Hg while treated with high-flow nasal cannula oxygen therapy. INTERVENTIONS:. Periods of APP and semirecumbent position (SRP) were randomly applied for 2 hours and separated by a 2-hour washout period. MEASUREMENTS AND MAIN RESULTS:. Arterial blood gases, end-tidal CO2. and esophageal pressure were recorded prior to and at the end of each period. Inspiratory muscle effort was assessed by measuring the esophageal pressure swing (∆PES) and the simplified esophageal pressure–time product (sPTPES). The other endpoints included physiologic dead space to tidal volume ratio (VD/VT) and the transpulmonary pressure swing. The APP increased the Pao2/Fio2 from 84 Torr (61–137 Torr) to 208 Torr (114–226 Torr) (p = 0.0007) and decreased both the VD/VT and the respiratory rate from 0.54 (0.47–0.57) to 0.49 (0.45–0.53) (p = 0.012) and from 26 breaths/min (21–30 breaths/min) to 21 breaths/min (19–22 breaths/min), respectively (p = 0.002). These variables remained unchanged during the SRP. The ∆PES and sPTPES per breath were unaffected by the position. However, the APP reduced the sPTPES per minute from 225 cm H2O.s.m–1 (176–332 cm H2O.s.m–1) to 174 cm H2O.s.m–1 (161–254 cm H2O.s.m–1) (p = 0.049). CONCLUSIONS:. In spontaneously breathing patients with COVID-19–associated AHRF supported by high-flow nasal oxygen, the APP improves oxygenation and reduces the physiologic dead space, respiratory rate, and work of breathing per minute.

Le COVID-19 peut entraîner un syndrome de détresse respiratoire aiguë (SDRA). Chez les patients intubés atteints de SDRA sévère, des séances précoces, prolongées et répétées de décubitus ventral (DV) réduisent la mortalité. Le DV vigile en dehors de la réanimation est faisable, améliore l'oxygénation et pourrait prévenir une aggravation respiratoire [1]. L'objectif principal de l'étude était d'étudier l'augmentation du support ventilatoire chez les patients avec une pneumonie hypoxémiante à COVID-19 faisant du DV vigile. Nous avons réalisé une étude de cohorte rétrospective bicentrique exposée/non exposée avec score de propension chez les patients en dehors de la réanimation avec pneumonie hypoxémiante a COVID-19 entre le 20 mars et le 20 avril 2020, à l'hôpital d'Aix-en-Provence et l'hôpital Nord de Marseille. Les critères d'inclusion étaient : l'insuffisance respiratoire hypoxémique nécessitant une supplémentation en oxygène, soit par oxygénothérapie conventionnelle, soit oxygène à haut débit (OHD), et un COVID-19 confirmé par PCR. Deux stratégies de traitement ont été comparées : le DV vigile 3 heures par jour pendant trois jours consécutifs (groupe DV) et aucune instruction concernant le positionnement ou une mauvaise tolérance du DV (groupe non-DV). Sur les 414 patients confirmés en PCR, 168 patients étaient éligibles et 48 ont fait du DV 3 h par jour pendant trois jours contre 120 le groupe non-DV. Après score de propension, 96 patients ont été analysés (48 patients dans chaque groupe). Tous les patients recevant du DV ont été appariés avec succès avec un patient sans DV. Les patients ont eu du DV pendant 6,9 (± 5,2) jours. Parmi les 48 patients du groupe DV, 32 (67%) ont eu du DV pendant 3 à 8 heures par jour et 16 (32%) pendant plus de 8 heures par jour. Pour le critère de jugement principal, 15 patients (31,2%) du groupe DV ont eu une augmentation de leur support ventilatoire à j14, contre 30 (62,5%) dans le groupe sans DV (p = 0,002) avec un hazard ratio (HR) de 2,59 (IC95% : 1,39–4,84). Pas de différence retrouvée sur la mortalité ou sur les taux d'intubation. Pas d'évènement indésirable majeur. Le DV vigile 3 h par jour pendant 3 jours consécutifs pourrait prévenir l'augmentation du support ventilatoire chez les patients atteints d'une pneumonie hypoxémiante à COVID 19.

Background Appropriate hand hygiene (HH) is key to reducing healthcare-acquired infections. The World Health Organization (WHO) recommends education and training to improve HH knowledge and compliance. Physicians are ranked among the worst of all healthcare workers for compliant handrubbing with its origin probably being the failure to learn this essential behavior during undergraduate medical studies. This study evaluated if the use of Ultraviolet-cabinets (UVc) for fluorescent-alcohol-based handrubs (AHR) during an undergraduate medical student training improved the compliance rate to the WHO hand hygiene recommendations (completeness of AHR application and HH opportunities). Methods This randomized trial compared a HH training with personal feedback (using UVc) to a control group. The first year, the students (2nd degree) were convened by groups (clusters) of 6–9 for a demonstration of the correct execution of WHO procedure. Randomization by cluster was done prior HH training. In the control group, the students hand rubbed under visual supervision of a tutor. In the intervention group after the same visual supervision, completeness of fluorescent-AHR hand application was recorded under UVc and was shown to the student. The intervention group had free access to the UVc until complete application. HH practices were included in simulation sessions for the both groups. One year after (3rd degree), all the students were asked to hand rub with fluorescent-AHR. A tutor (blinded to the study group) assessed the completeness of hand application under UVc and the compliance with the WHO opportunities. Complete application of AHR was defined as fluorescence for all the surfaces of hands and wrists. Results 242 students participated (140 in the intervention group and 102 in the control group). One year after the initial training, the rate of complete application of AHR was doubled in the intervention group (60.0% vs. 30.4%, p < 0.001). In a multivariate analysis which included gender, additional HH or UVc training, surgical traineeship and regular use of AHR, the hazard ratio for the intervention was 3.84 (95%CI: 2.09–7.06). The compliance with the HH WHO’s opportunities was increased in the intervention group (58.1% vs. 42.4%, p < 0.018). Conclusion Using UVc for undergraduate medical students education to hand hygiene improves their technique and compliance with WHO recommendations.

This case series describes the proportion of awake, nonintubated inpatients with COVID-19 and hypoxemic respiratory failure requiring oxygen supplementation whose Pa o 2 increased ≥20% with prone positioning, and their respiratory status after resuming supine positioning.

This single-center case series investigated the effect of almitrine infusion on Pa o 2 /fraction of inspired oxygen (F io 2 ) in 25 patients on veno-venous extracorporeal membrane oxygenation for severe acute respiratory distress syndrome. A positive trial was defined as an increase of Pa o 2 /F io 2 ratio ≥20%. Thirty-two trials were performed. Twenty (62.5%, 95% confidence interval, 37.5%–75%) trials in 18 patients were positive, with a median Pa o 2 /F io 2 ratio increase of 35% (25%–43%). A focal acute respiratory distress syndrome and inhaled nitric oxide therapy were more frequent in patients with a positive response to almitrine. We observed no complications of almitrine use.

Background: The link between bacterial resistance and prognosis remains controversial. Predominant pathogen causing ventilator-associated pneumonia (VAP) is Pseudomonas aeruginosa (Pa), which has increasingly become multidrug resistant (MDR). The aim of this study was to evaluate the relationship between MDR VAP Pa episodes and 30-day mortality. Methods: From a longitudinal prospective French multicenter database (2010-2016), Pa VAP onset and physiological data were recorded. MDR was defined as non-susceptibility to at least 1 agent in 3 or more antimicrobial categories. To analyze if MDR episodes were associated with greater in-hospital 30-day mortality, we performed a multivariate survival analysis using the multivariate nonlinear frailty model. Results: A total of 230 patients presented 286 Pa VAP. A maximum of 3 episodes per patient was observed; 73 episodes were MDR and 213 were susceptible. In the multivariate model, factors independently associated with 30-day mortality included hospitalization in the 6 months preceding the first episode (hazard ratio [HR], 2.31; 95% confidence interval [CI], 1.50-3.60; P = .0002), chronic renal failure (HR, 2.34; 95% CI, 1.15-4.77; P = .0196), and Pa VAP recurrence (HR, 2.29; 95% CI, 1.79-4.87; P = .032). Finally, MDR Pa VAP was not associated with death (HR, 0.87; 95% CI; 0.52-1.45; P = .59). Conclusions: This study did not identify a relationship between the resistance profile of Pseudomonas aeruginosa and mortality. (C) 2019 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.

Central MessageThe fenestration of a tracheal Y-stent for a tracheostomy tube insertion can be proposed for the treatment of extensive injuries of the trachea in patients requiring mechanical ventilation. The fenestration of a tracheal Y-stent for a tracheostomy tube insertion can be proposed for the treatment of extensive injuries of the trachea in patients requiring mechanical ventilation. Iatrogenic tracheal injury (ITI) is a severe complication of tracheostomy procedures, responsible for 15.5% of deaths associated with tracheostomy. Because the incidence of such an event is rare, the management of ITI is guided only by anecdotal experiences and case series. We report our experience of a new procedure to treat life-threatening ITI after surgical tracheostomy. The patient gave her consent to scientific communication and the Committee for the Protection of Persons waived the necessity of an approval from our institution's ethics committee. A 45-year-old woman was referred to our center for severe acute respiratory distress syndrome and a history of morbid obesity (body mass index, 49). After 11 days of mechanical ventilation (MV), a tracheostomy was indicated for difficult weaning from the ventilator. An open procedure with an inverted T-incision of the trachea was performed. Due to a short and thick neck, the resulting tract was long and distorted. Unintentional movements of the tube cuff caused a 3-cm defect extending from the middle to the lower half of the anterior wall, with an inferior margin at 4 cm from the carina (Figure 1). It became impossible to inflate the tube cuff beyond the defect without inducing a selective ventilation of the right stem bronchus. An orotracheal tube was reinserted to avoid further aggravation; however, considerable and rapidly life-threatening air leaks occurred. The decision was made to perform a new salvage procedure. A silicone Y-stent was inserted through a rigid bronchoscopy to cover the ITI (GSS Y 16/13/13; Novatech, La Ciotat, France). The stent was then surgically approached through the initial cervicotomy used for the tracheostomy; a fenestration was created inside the stent, close to the upper margin of the ITI. A tracheal tube with an inner cannula (Uniperc Portex 7.0 mm 100/897/070; Smiths Medical, Minneapolis, Minn) was inserted, under bronchoscopic guidance, through the stent fenestration (Figure 2, A) (Video 1), with its distal edge placed above the carina (Figure 2, B). At the end of the procedure, MV was efficient with no residual air leaks.Figure 2A, The tracheostomy tube passing through the anterior wall of the Y stent. B, The distal edge of the tube above the carina, inside the stent. C, The subnormal tracheal lumen after removal of the Y-stent. D, The removed fenestrated Y-stent.View Large Image Figure ViewerDownload Hi-res image Download (PPT) After 54 days, complete weaning from ventilation was achieved. A new bronchoscopy found that the former ITI was completely healed, with no significant reduction of the tracheal diameter (Figure 2, C), allowing definitive removal of both the stent (Figure 2, D) and the tracheostomy tube. This is the first description of respiratory weaning with a tracheostomy tube inserted through a fenestration in a Y-stent. The treatment of ITI for patients requiring MV is challenging because positive pressure hinders conservative treatment. Surgical techniques present a very high risk to patients,1Hofmann H.S. Rettig G. Radke J. Neef H. Silber R.E. Iatrogenic ruptures of the tracheobronchial tree.Eur J Cardiothorac Surg. 2002; 21: 649-652Crossref PubMed Scopus (145) Google Scholar but are nevertheless often considered when the defect exceeds the limits of spontaneous repair.2Udelsman B.V. Eaton J. Muniappan A. Morse C.R. Wright C.D. Mathisen D.J. Repair of large airway defects with bioprosthetic materials.J Thorac Cardiovasc Surg. 2016; 152: 1388-1397Abstract Full Text Full Text PDF PubMed Scopus (20) Google Scholar The safest solution is to bridge the ITI until tracheal healing is achieved. However, for lesions too close to the carina this cannot be achieved simply by advancing the endotracheal tube beyond the injury. In such situations, Marquette and colleagues3Marquette C.H. Bocquillon N. Roumilhac D. Nevière R. Mathieu D. Ramon P. Conservative treatment of tracheal rupture.J Thorac Cardiovasc Surg. 1999; 117: 399-401Abstract Full Text Full Text PDF PubMed Scopus (40) Google Scholar proposed to insert, through a tracheostomy, a 6-mm bronchial tube in each main stem bronchus with a nasotracheal tube left for security and for the suction of oropharyngeal secretions. Our stenting approach is an adaptation of the technique originally described by Tazi-Mezalek and colleagues4Tazi-Mezalek R. Musani A. Laroumagne S. Astoul P.J. D'Journo X.B. Thomad P.A. et al.Airway stenting in the management of iatrogenic tracheal injuries: 10-Year experience.Respirol Carlton Vic. 2016; 21: 1452-1458Crossref PubMed Scopus (33) Google Scholar in 7 patients with ITI localized in the lower part of the trachea. This technique focuses on extensive ITI, from the middle to the lower part of the trachea, when a tracheostomy is essential for weaning from MV. During the procedure, ensuring adequate ventilation is challenging in populations such as patients with acute respiratory distress syndrome. High-frequency jet ventilation should be used cautiously because of the risks of barotrauma, hypercapnia, and hemodynamic impairment.5Fernandez-Bustamante A. Ibañez V. Alfaro J.J. de Miguel E. German M.J. Mayo A. et al.High-frequency jet ventilation in interventional bronchoscopy: factors with predictive value on high-frequency jet ventilation complications.J Clin Anesth. 2006; 18: 349-356Crossref PubMed Scopus (42) Google Scholar The fenestration must be performed after the stent has been placed by bronchoscopy in the tracheal tree, ensuring that the fenestration is far enough from the carina and to avoid selective lung ventilation but remain in the ITI to prevent an increase of the defect. For safety reasons, the choice of a tracheal tube with an inner cannula seems of paramount importance to avoid further high-risk cannula changes. In addition to general preventive measures, including rigorous surgical technique, careful sizing of the tube, and enhanced fixation, bronchoscopic control of the trachea above the tracheal hole may help prevent such events. Endoscopic management of extensive defects of the anterior tracheal wall with a fenestrated Y-stent is a promising minimally invasive option in patients who require MV.

To investigate whether neuromuscular blocking agents (NMBA) exert beneficial effects in acute respiratory distress syndrome (ARDS) by reason of their action on respiratory mechanics, particularly transpulmonary pressures (P L).

Nosocomial infections occurring during extracorporeal membrane oxygenation (ECMO) support have already been reported, but few studied infections directly related to ECMO devices. This study aims to evaluate the rate of both colonisations and infections related to ECMO devices at the time of ECMO removal.

We report the first case of organ-transmitted varicella reinfection in a lung transplant patient who had previously contracted primary varicella during childhood. CASE REPORT A 62-year-old woman with diffuse bronchiectasis was admitted to our Intensive care unit after lung transplantation complicated by grade 3 primary graft dysfunction. The donor was a 31-year-old man deceased from a stroke due to an intracranial arteriovenous malformation. The patient was varicella zoster virus (VZV) seropositive but had never developed herpes zoster. Anti-infectious treatment with imipeneme-cilastatine, colimycine, and voriconazole was started during surgery based on previous microbiological information (cured aspergillosis and current colonization with multiple-drug–resistant Achromobacter xylosoxidans). Because both the patient and donor were seronegative for cytomegalovirus and herpes simplex virus, the patient did not receive antiviral prophylaxis per our protocol. She had received induction therapy with rabbit antithymocyte globulin and an immunosuppressive regimen with cyclosporine and methylprednisone. Due to the persistent respiratory failure, a bronchoalveolar lavage with extensive microbiological investigations was performed on day 3. On day 6, sudden septic shock without fever or examination signs occurred. Central hypovolemia and normal cardiac function were assessed by echocardiography. Worsening of bilateral opacities visible on chest X-ray was the only substantial finding. Empirical ganciclovir treatment was started subsequently. On day 7, a screening for VZV infection conducted on day 6 by quantitative blood polymerase chain reaction (PCR) analysis was positive with a viral load of 4.2 × 104 copies/mL. Although the treatment drug was changed to acyclovir the patient developed a multiorgan failure and died on day 9. She never developed skin eruption. The PCR results from the bronchoalveolar lavage and the postmortem lung biopsies were positive for VZV with viral loads of respectively 10.4 × 107 copies/mL and 9.7 × 106 VZV copies/millions of cells. Histologic analyses were consistent with VZV infection (Figure 1) without cell rejection. Anti-HLA antibodies were undetectable on day 5.FIGURE 1: The lung biopsy histological examination was highly suggestive of VZV infection (confirmed by PCR done on the lung biopsy) with few cells presenting intranuclear inclusion bodies. There was an associated diffuse acute interstitial inflammatory infiltrate with patterns of diffuse alveolar damage with hyaline membranes (acute respiratory distress syndrome). There were no signs of acute rejection (hematoxylin-eosin saffron staining, ×20). Image courtesy of Mr. Brandone.Despite the absence of symptoms and the immunoglobulin G and M seronegativity of the donor, we performed VZV-specific PCR analysis of donor lung biopsies and blood samples. Both were positive. Neither the patient nor the donor had received a VZV vaccine. We concluded that death occurred consecutive to VZV reinfection. DISCUSSION To our knowledge, this is the first description of an organ-transmitted VZV infection to a VZV seropositive recipient. The first case of organ-transmitted varicella was reported after pediatric cardiac transplantation, but the receiver was VZV seronegative, and the donor had been recently treated for primary varicella.1 Previous cases of clinical reinfection have been rarely reported in immunocompromised patients.2 As suggested in an experimental model,3 exposure to a concentrated inoculum from a viremic donor along with severe T-cell depletion may have favored a rapid and severe dissemination. It may also explain the unusual presentation with septic shock as the sole manifestation of infection. The fatal evolution is consistent with the high mortality reported in cases of disseminated VZV infection without skin eruption in the context of lung transplantation.4 As such presentation could hardly have been prevented, it highlights the susceptibility of solid organ recipients to herpes viruses and indicates the need for broad suspicion, screening and early empiric treatment.

Neuromuscular blocking agents (NMBAs) have been shown to improve the outcome of the most severely hypoxemic, acute respiratory distress syndrome (ARDS) patients. However, the recommended dosage as well as the necessity of monitoring the neuromuscular block is unknown. We aimed to evaluate the efficiency of a nurse-directed protocol of NMBA administration based on a train-of-four (TOF) assessment to ensure a profound neuromuscular block and decrease cisatracurium consumption compared to an elevated and constant dose regimen. A prospective open labeled study was conducted in two medical intensive care units of two French university hospitals. Consecutive ARDS patients with a PaO2/FiO2 ratio less than 120 with a PEEP ≥5 cm H2O were included. Cisatracurium administration was driven by the nurses according to an algorithm based on TOF monitoring. The primary endpoint was cisatracurium consumption. The secondary endpoints included the quality of the neuromuscular block, the occurrence of adverse events, and the evolution of ventilatory and blood gas parameters.

Background The relationship between tiredness and the risk of medical errors is now commonly accepted. The main objective of this study was to assess the impact of an intensive care unit (ICU) night shift on the cognitive performance of a group of intensivists. The influence of professional experience and the amount of sleep on cognitive performance was also investigated. Methods A total of 51 intensivists from three ICUs (24 seniors and 27 residents) were included. The study participants were evaluated after a night of rest and after a night shift according to a randomized order. Four cognitive skills were tested according to the Wechsler Adult Intelligence Scale and the Wisconsin Card Sorting Test. Results All cognitive abilities worsened after a night shift: working memory capacity (11.3 ± 0.3 vs. 9.4 ± 0.3; p < 0.001), speed of processing information (13.5 ± 0.4 vs. 10.9 ± 0.3; p < 0.001), perceptual reasoning (10.6 ± 0.3 vs. 9.3 ± 0.3; p < 0.002), and cognitive flexibility (41.2 ± 1.2 vs. 44.2 ± 1.3; p = 0.063). There was no significant difference in terms of level of cognitive impairment between the residents and ICU physicians. Only cognitive flexibility appeared to be restored after 2 h of sleep. The other three cognitive skills were altered, regardless of the amount of sleep during the night shift. Conclusions The cognitive abilities of intensivists were significantly altered following a night shift in the ICU, regardless of either the amount of professional experience or the duration of sleep during the shift. The consequences for patients’ safety and physicians’ health should be further evaluated.

Approximately 20 years have passed since we reported our results of histologically proven cytomegalovirus (CMV) pneumonia in non-immunocompromised ICU patients. Even if there are more recent reports suggesting that CMV may worsen the outcomes for ICU patients, there is no definite answer to this question: is CMV a potential pathogen for ICU patients or is it simply a bystander?

INTRODUCTION:Bilirubin is well-recognized marker of hepatic dysfunction in intensive care unit (ICU) patients. Multiple organ failure often complicates acute respiratory distress syndrome (ARDS) evolution and is associated with high mortality. The effect of early hepatic dysfunction on ARDS mortality has been poorly investigated. We evaluated the incidence and the prognostic significance of increased serum bilirubin levels in the initial phase of ARDS.METHODS:The data of 805 patients with ARDS were retrospectively analysed. This population was extracted from two recent multicenter, prospective and randomised trials. Patients presenting with ARDS with a ratio of the partial pressure of arterial oxygen to the fraction of inspired oxygen < 150 mmHg measured with a PEEP ≥ 5 cm of water were included. The total serum bilirubin was measured at inclusion and at days 2, 4, 7 and 14. The primary objective was to analyse the bilirubin at inclusion according to the 90-day mortality rate.RESULTS:The 90-day mortality rate was 33.8% (n = 272). The non-survivors were older, had higher Sepsis-related Organ Failure Assessment (SOFA) score and were more likely to have a medical diagnosis on admission than the survivors. At inclusion, the SOFA score without the liver score (10.3±2.9 vs. 9.0±3.0, p<0.0001) and the serum bilirubin levels (36.1±57.0 vs. 20.5±31.5 μmol/L, p<0.0001) were significantly higher in the non-survivors than in the survivors. Age, the hepatic SOFA score, the coagulation SOFA score, the arterial pH level, and the plateau pressure were independently associated with 90-day mortality in patients with ARDS.CONCLUSION:Bilirubin used as a surrogate marker of hepatic dysfunction and measured early in the course of ARDS was associated with the 90-day mortality rate.

Objectives: Cytomegalovirus (CMV) reactivation in intensive care unit patients may increase mortality and favour bacterial pneumonia. We developed a murine model to compare the severity of staphylococcal pneumonia after CMV reactivation and in CMV-negative mice.Methods: Balb/c mice were primo-infected with murine cytomegalovirus (MCMV n = 90) or received saline (control n = 90). After latency, all mice underwent caecal ligation and puncture to trigger MCMV reactivation in MCMV primary-infected mice. Surviving animals received an intra-nasal inoculation with methicillin-susceptible Staphylococcus aureus (MSSA) to induce pneumonia. Mortality, lung bacterial count, histology and interferon-alpha and gamma serum levels were compared in MCMV reactivated and control mice 2, 5 and 15 days after pneumonia.Results: AfterMSSA pneumonia, MCMV mice showed a trend towards a higher mortality (9.4% versus 0%; p 0.09) and a higher weight loss (2.2 (0.6-4.1 g) versus 0.7 (-0.3 to 1.3 g); p 0.005). The lung bacterial countwas higher in MCMV mice 2 days (5 x 10(3) (10(3) to 3 x 10(5)) versus 10(2) (0 to 4 x 10(2)) CFU/lung; p 0.007) and 5 days (2.5 x 10(4) (1.6 x 10(4) to 6.5 x 10(5)) versus 15 (10-40) CFU/lung; p 0.005) after MSSA pneumonia. 8/40 (20%) MCMV mice developed lung abscesses compared to 0% in control (p 0.011). Interferon-alpha serum levels 2 days after staphylococcal pneumonia were higher in MCMV mice.Conclusions: MCMV reactivation decreased lung bacterial clearance and favoured the development of staphylococcal abscessing pneumonia. CMV reactivation may be responsible for a higher susceptibility to bacterial sepsis. (C) 2016 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Le cytomégalovirus (CMV) est un virus ubiquitaire. L'infection à CMV est liée soit à une primo-infection, soit à une réactivation. Celle-ci est provoquée par un « stress » qui va consommer les ressources du système immunitaire (SI) et permettre la réplication virale, ou à un déficit de ce même SI. Chez le patient de réanimation, l'infection à CMV est associée à une augmentation de la durée de séjour en réanimation, de la durée de ventilation mécanique, de la mortalité [1]. Le patient brûlé grave est caractérisé par une immunodépression acquise multifactorielle. Sur des modèles murins, il a été montré que les sujets brûlés étaient susceptibles de présenter une infection à CMV [2]. D'un point de vue clinique, elle reste encore mal documentée chez ces patients. L'objectif de notre étude était d'évaluer l'incidence de l'infection à CMV chez les patients brûlés graves. Nous avons inclus les patients avec une surface cutanée brûlée (SCB) supérieure à 15 % admis dans le centre de traitement des brûlés de l'HIA Sainte-Anne, Toulon, entre septembre 2008 et septembre 2011. Une sérologie CMV était réalisée à l'admission, puis une détection de la virémie par real time quantitative PCR (RTqPCR) était effectuée une à deux fois par semaine pendant le séjour en réanimation. L'infection à CMV était définie par une RTqPCR positive en cours de séjour. La réactivation du CMV était définie par une RTqPCR positive chez un patient séropositif à l'admission. Au total, 58 patients étaient inclus. L'âge moyen des patients était de 51 ± 21 ans. La SCB moyenne était de 31 ± 15 %. La brûlure était d'origine thermique dans 89 % des cas. 36 patients étaient séropositifs pour le CMV à l'admission, 20 séronégatifs (64 % et 36 % respectivement). Une infection à CMV était diagnostiquée chez 22 des patients séropositifs (61 %), et chez un seul des patients séronégatifs (5 %). L'infection à CMV était plus fréquente chez le patient séropositive que séronégatif (p < 0,0001). Chez les patients séropositifs, l'infection à CMV était associée à un âge supérieur (p = 0,03), à une durée de séjour moyenne prolongée en réanimation (53 jours versus 28 jours, p = 0,02). La SCB n'était pas différente (33 % versus 29 %, p = 0,5). Le taux de mortalité en réanimation n'était pas différent entre les patients ayant présenté une infection à CMV et les autres (27 % versus 21 %, p = 1). Notre étude montre que l'infection à CMV est plus fréquente chez le patient séropositif pour le CMV à l'admission que chez le patient séronégatif, suggérant que le mécanisme de cette infection est principalement lié à une réactivation plutôt qu'une primo-infection. Chez le patient brûlé séropositif, l'infection à CMV est fréquente, 61 % dans notre cohorte. Cette incidence est supérieure à celle observée dans d'autres groupes de patients de réanimation. En analyse statistique univariée, l'infection à CMV chez ces patients est associée à une durée de séjour en réanimation prolongée. Sur ces données, il n'est pas possible de déterminer si l'infection à CMV est la cause de l'augmentation de durée de séjour, ou bien la conséquence. En revanche, nous n'avons pas observé d'impact sur la mortalité.