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Background: Postoperative pulmonary complications is a major issue that affects outcomes of surgical patients. The hypothesis was that the intraoperative ventilation parameters are associated with occurrence of postoperative pulmonary complications., Methods: A single-center retrospective cohort study was conducted at the Lille University Hospital, France. The study included 33,701 adults undergoing noncardiac, nonthoracic elective surgery requiring general anesthesia with tracheal intubation between January 2010 and December 2019. Intraoperative ventilation parameters were compared between patients with and without one or more postoperative pulmonary complications (respiratory infection, respiratory failure, pleural effusion, atelectasis, pneumothorax, bronchospasm, and aspiration pneumonitis) within 7 days of surgery., Results: Among 33,701 patients, 2,033 (6.0%) had one or more postoperative pulmonary complications. The lower tidal volume to predicted body weight ratio (odds ratio per -1 ml·kgPBW-1, 1.08; 95% CI, 1.02 to 1.14; P < 0.001), higher mechanical power (odds ratio per 4 J·min-1, 1.37; 95% CI, 1.26 to 1.49; P < 0.001), dynamic respiratory system compliance less than 30 ml·cm H2O (1.30; 95% CI, 1.15 to 1.46; P < 0.001), oxygen saturation measured by pulse oximetry less than 96% (odds ratio, 2.42; 95% CI, 1.97 to 2.96; P < 0.001), and lower end-tidal carbon dioxide (odds ratio per -3 mmHg, 1.06; 95% CI, 1.00 to 1.13; P = 0.023) were independently associated with postoperative pulmonary complications. Patients with postoperative pulmonary complications were more likely to be admitted to the intensive care unit (odds ratio, 12.5; 95% CI, 6.6 to 10.1; P < 0.001), had longer hospital length of stay (subhazard ratio, 0.43; 95% CI, 0.40 to 0.45), and higher in-hospital (subhazard ratio, 6.0; 95% CI, 4.1 to 9.0; P < 0.001) and 1-yr mortality (subhazard ratio, 2.65; 95% CI, 2.33 to 3.02; P < 0.001)., Conclusions: In the study's population, decreased rather than increased tidal volume, decreased compliance, increased mechanical power, and decreased end-tidal carbon dioxide were independently associated with postoperative pulmonary complications., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc., on behalf of the American Society of Anesthesiologists.)

Biofilms are highly tolerant to antimicrobials and host immune defense, enabling pathogens to thrive in hostile environments. The diversity of microbial biofilm infections requires alternative and complex treatment strategies. In a previous work we demonstrated that the human Atrial Natriuretic Peptide (hANP) displays a strong anti-biofilm activity toward Pseudomonas aeruginosa and that the binding of hANP by the AmiC protein supports this effect. This AmiC sensor has been identified as an analog of the human natriuretic peptide receptor subtype C (h-NPRC). In the present study, we evaluated the anti-biofilm activity of the h-NPRC agonist, osteocrin (OSTN), a hormone that displays a strong affinity for the AmiC sensor at least in vitro . Using molecular docking, we identified a pocket in the AmiC sensor that OSTN reproducibly docks into, suggesting that OSTN might possess an anti-biofilm activity as well as hANP. This hypothesis was validated since we observed that OSTN dispersed established biofilm of P. aeruginosa PA14 strain at the same concentrations as hANP. However, the OSTN dispersal effect is less marked than that observed for the hANP (-61% versus -73%). We demonstrated that the co-exposure of P. aeruginosa preformed biofilm to hANP and OSTN induced a biofilm dispersion with a similar effect to that observed with hANP alone suggesting a similar mechanism of action of these two peptides. This was confirmed by the observation that OSTN anti-biofilm activity requires the activation of the complex composed by the sensor AmiC and the regulator AmiR of the ami pathway. Using a panel of both P. aeruginosa laboratory reference strains and clinical isolates, we observed that the OSTN capacity to disperse established biofilms is highly variable from one strain to another. Taken together, these results show that similarly to the hANP hormone, OSTN has a strong potential to be used as a tool to disperse P. aeruginosa biofilms., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Lesouhaitier Olivier reports financial support was provided by 10.13039/501100007527University of Rouen Normandy. Lesouhaitier Olivier reports a relationship with 10.13039/501100007527University of Rouen Normandy that includes: employment and funding grants. Lesouhaitier Olivier has patent issued to Licensee. No conflict of interest., (© 2023 The Authors.)

We report in vivo development of cefiderocol (FDC) resistance among four sequential Pseudomonas aeruginosa clinical isolates ST244 recovered from a single patient, without exposure to FDC, which raises concern about the effectiveness of this novel drug. The first recovered P. aeruginosa isolate (P-01) was susceptible to FDC (2 μg/mL), albeit this MIC value was higher than that of a wild-type P. aeruginosa (0.12-0.25 μg/ml). The subsequent isolated strains (P-02, P-03, P-04) displayed increasing levels of FDC MICs (8, 16, and 64 μg/ml, respectively). Those isolates also showed variable and gradual increasing levels of resistance to most β-lactams tested in this study. Surprisingly, no acquired β-lactamase was identified in any of those isolates. Whole-genome sequence analysis suggested that this resistance was driven by multifactorial mechanisms including mutational changes in iron transporter proteins associated with FDC uptake, ampC gene overproduction, and mexAB-oprM overexpression. These findings highlight that a susceptibility testing to FDC must be performed prior to any prescription., (© 2022. The Author(s).)

Importance: The benefit of high-dose dexamethasone and oxygenation strategies vs standard of care for patients with severe acute hypoxemic respiratory failure (AHRF) caused by COVID-19 pneumonia is debated., Objectives: To assess the benefit of high-dose dexamethasone compared with standard of care dexamethasone, and to assess the benefit of high-flow nasal oxygen (HFNo2) or continuous positive airway pressure (CPAP) compared with oxygen support standard of care (o2SC)., Design, Setting, and Participants: This multicenter, placebo-controlled randomized clinical trial was conducted in 19 intensive care units (ICUs) in France from April 2020 to January 2021. Eligible patients were consecutive ICU-admitted adults with COVID-19 AHRF. Randomization used a 2 × 3 factorial design for dexamethasone and oxygenation strategies; patients not eligible for at least 1 oxygenation strategy and/or already receiving invasive mechanical ventilation (IMV) were only randomized for dexamethasone. All patients were followed-up for 60 days. Data were analyzed from May 26 to July 31, 2021., Interventions: Patients received standard dexamethasone (dexamethasone-phosphate 6 mg/d for 10 days [or placebo prior to RECOVERY trial results communication]) or high-dose dexamethasone (dexamethasone-phosphate 20 mg/d on days 1-5 then 10 mg/d on days 6-10). Those not requiring IMV were additionally randomized to o2SC, CPAP, or HFNo2., Main Outcomes and Measures: The main outcomes were time to all-cause mortality, assessed at day 60, for the dexamethasone interventions, and time to IMV requirement, assessed at day 28, for the oxygenation interventions. Differences between intervention groups were calculated using proportional Cox models and expressed as hazard ratios (HRs)., Results: Among 841 screened patients, 546 patients (median [IQR] age, 67.4 [59.3-73.1] years; 414 [75.8%] men) were randomized between standard dexamethasone (276 patients, including 37 patients who received placebo) or high-dose dexamethasone (270 patients). Of these, 333 patients were randomized among o2SC (109 patients, including 56 receiving standard dexamethasone), CPAP (109 patients, including 57 receiving standard dexamethasone), and HFNo2 (115 patients, including 56 receiving standard dexamethasone). There was no difference in 60-day mortality between standard and high-dose dexamethasone groups (HR, 0.96 [95% CI, 0.69-1.33]; P = .79). There was no significant difference for the cumulative incidence of IMV criteria at day 28 among o2 support groups (o2SC vs CPAP: HR, 1.08 [95% CI, 0.71-1.63]; o2SC vs HFNo2: HR, 1.04 [95% CI, 0.69-1.55]) or 60-day mortality (o2SC vs CPAP: HR, 0.97 [95% CI, 0.58-1.61; o2SC vs HFNo2: HR, 0.89 [95% CI, 0.53-1.47]). Interactions between interventions were not significant., Conclusions and Relevance: In this randomized clinical trial among ICU patients with COVID-19-related AHRF, high-dose dexamethasone did not significantly improve 60-day survival. The oxygenation strategies in patients who were not initially receiving IMV did not significantly modify 28-day risk of IMV requirement., Trial Registration: ClinicalTrials.gov Identifier: NCT04344730; EudraCT: 2020-001457-43.

Disabled people are often involved in robotics research as potential users of technologies which address specific needs. However, their more generalised lived expertise is not usually included when planning the overall design trajectory of robots for health and social care purposes. This risks losing valuable insight into the lived experience of disabled people, and impinges on their right to be involved in the shaping of their future care. This project draws upon the expertise of an interdisciplinary team to explore methodologies for involving people with disabilities in the early design of care robots in a way that enables incorporation of their broader values, experiences and expectations. We developed a comparative set of focus group workshops using Community Philosophy, LEGO® Serious Play® and Design Thinking to explore how people with a range of different physical impairments used these techniques to envision a "useful robot". The outputs were then workshopped with a group of roboticists and designers to explore how they interacted with the thematic map produced. Through this process, we aimed to understand how people living with disability think robots might improve their lives and consider new ways of bringing the fullness of lived experience into earlier stages of robot design. Secondary aims were to assess whether and how co-creative methodologies might produce actionable information for designers (or why not), and to deepen the exchange of social scientific and technical knowledge about feasible trajectories for robotics in health-social care. Our analysis indicated that using these methods in a sequential process of workshops with disabled people and incorporating engineers and other stakeholders at the Design Thinking stage could potentially produce technologically actionable results to inform follow-on proposals., Competing Interests: Author JM was employed by company IBM Global. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 de Saille, Kipnis, Potter, Cameron, Webb, Winter, O’Neill, Gold, Halliwell, Alboul, Bell, Stratton and McNamara.)

Pseudomonas aeruginosa biofilms cause chronic, antibiotic tolerant infections in wounds and lungs. Numerous recent studies demonstrate that bacteria can detect human communication compounds through specific sensor/receptor tools that modulate bacterial physiology. Consequently, interfering with these mechanisms offers an exciting opportunity to directly affect the infection process. It is shown that the human hormone Atrial Natriuretic Peptide (hANP) both prevents the formation of P. aeruginosa biofilms and strongly disperses established P. aeruginosa biofilms. This hANP action is dose-dependent with a strong effect at low nanomolar concentrations and takes effect in 30-120 min. Furthermore, although hANP has no antimicrobial effect, it acts as an antibiotic adjuvant. hANP enhances the antibiofilm action of antibiotics with diverse modes of action, allowing almost full biofilm eradication. The hANP effect requires the presence of the P. aeruginosa sensor AmiC and the AmiR antiterminator regulator, indicating a specific mode of action. These data establish the activation of the ami pathway as a potential mechanism for P. aeruginosa biofilm dispersion. hANP appears to be devoid of toxicity, does not enhance bacterial pathogenicity, and acts synergistically with antibiotics. These data show that hANP is a promising powerful antibiofilm weapon against established P. aeruginosa biofilms in chronic infections., (© 2022 The Authors. Advanced Science published by Wiley-VCH GmbH.)

Background: Deviation from guidelines is frequent in emergency situations, and this may lead to increased mortality. Probably because of time constraints, 55% is the greatest reported guidelines compliance rate in severe trauma patients. This study aimed to identify among all available recommendations a reasonable bundle of items that should be followed to optimize the outcome of hemorrhagic shocks (HSs) and severe traumatic brain injuries (TBIs)., Methods: We first estimated the compliance with French and European guidelines using the data from the French TraumaBase registry. Then, we used a machine learning procedure to reduce the number of recommendations into a minimal set of items to be followed to minimize 7-day mortality. We evaluated the bundles using an external validation cohort., Results: This study included 5,924 trauma patients (1,414 HS and 4,955 TBI) between 2011 and August 2019 and studied compliance to 36 recommendation items. Overall compliance rate to recommendation items was 71.6% and 66.9% for HS and TBI, respectively. In HS, compliance was significantly associated with 7-day decreased mortality in univariate analysis but not in multivariate analysis (risk ratio [RR], 0.91; 95% confidence interval [CI], 0.90-1.17; p = 0.06). In TBI, compliance was significantly associated with decreased mortality in univariate and multivariate analysis (RR, 0.85; 95% CI, 0.75-0.92; p = 0.01). For HS, the bundle included 13 recommendation items. In the validation cohort, when this bundle was applied, patients were found to have a lower 7-day mortality rate (RR, 0.46; 95% CI, 0.27-0.63; p = 0.01). In TBI, the bundle included seven items. In the validation cohort, when this bundle was applied, patients had a lower 7-day mortality rate (RR, 0.55; 95% CI, 0.34-0.71; p = 0.02)., Discussion: Using a machine-learning procedure, we were able to identify a subset of recommendations that minimizes 7-day mortality following traumatic HS and TBI. These two bundles remain to be evaluated in a prospective manner., Level of Evidence: Care Management, level II., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Colonization resistance by gut microbiota is a fundamental phenomenon in infection prevention and control. Hospitalized patients may be exposed to multi-drug-resistant bacteria when hand hygiene compliance among healthcare workers is not adequate. An additional layer of defence is provided by the healthy gut microbiota, which helps clear the exogenous bacteria and acts as a safety net when hand hygiene procedures are not followed. This narrative review focuses on the role of the gut microbiota in colonization resistance against multi-drug-resistant bacteria, and its implications for infection control. The review discusses the underlying mechanisms of colonization resistance (direct or indirect), the concept of resilience of the gut microbiota, the link between the antimicrobial spectrum and gut dysbiosis, and possible therapeutic strategies. Antimicrobial stewardship is crucial to maximize the effects of colonization resistance. Avoiding unnecessary antimicrobial therapy, shortening the antimicrobial duration as much as possible, and favouring antibiotics with low anti-anaerobe activity may decrease the acquisition and expansion of multi-drug-resistant bacteria. Even after antimicrobial therapy, the resilience of the gut microbiota often occurs spontaneously. Spontaneous resilience explains the existence of a window of opportunity for colonization of multi-drug-resistant bacteria during or just after antimicrobial therapy. Strategies favouring resilience of the gut microbiota, such as high-fibre diets or precision probiotics, should be evaluated., (Copyright © 2021 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.)

Objectives: Postoperative infections occur frequently after pancreaticoduodenectomy, especially in patients with bile colonization. Recommendations for perioperative anti-infectious treatment are lacking, and clinical practice is heterogenous. We have analyzed the effects of bile colonization and antibiotic prophylaxis on postoperative infection rates, types and therapeutic consequences., Methods: Retrospective observational study in patients undergoing pancreaticoduodenectomy with intraoperative bile culture. Data on postoperative infections and non-infectious complications, bile cultures and antibiotic prophylaxis adequacy to biliary bacteria were collected., Results: Among 129 patients, 53% had a positive bile culture and 23% had received appropriate antibiotic prophylaxis. Postoperative documented infection rate was over 40% in patients with or without bile colonization, but antibiotic therapy was more frequent in positive bile culture patients (77% vs. 57%, P=0,008). The median duration of antibiotic therapy was 11 days and included a broad-spectrum molecule in 42% of cases. Two-thirds of documented postoperative infections involved one or more bacteria isolated in bile cultures, which was associated with a higher complication rate. While bile culture yielded Gram-negative bacilli (57%) and Gram-positive cocci (43%), fungal microorganisms were scarce. Adequate preoperative antibiotic prophylaxis according to bile culture was not associated with reduced infectious or non-infectious complication rates., Conclusion: Patients undergoing pancreaticoduodenectomy experience a high rate of postoperative infections, often involving bacteria from perioperative bile culture when positive, with no preventive effect of an adequate preoperative antibiotic prophylaxis. Increased postoperative complications in patients with bile colonization may render necessary a perioperative antibiotic treatment targeting bile microorganisms. Further prospective studies are needed to improve the anti-infectious strategy in these patients., (Copyright © 2021 Elsevier Masson SAS. All rights reserved.)

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Bacterial vaginosis (BV) diagnosis in pregnancy is based on the Nugent score, which consists of semiquantitation of bacterial morphotypes. Limited data exist concerning molecular-based diagnosis in asymptomatic pregnant women. Using high-throughput quantitative PCR, 34 microorganisms were screened in asymptomatic pregnant women and compared with the Nugent score. Three-hundred and four vaginal samples had a Nugent score <7 (69.9%) and 131, a Nugent score ≥7 (30.1%), consistent with BV. More pregnant women with BV share Atopobiumvaginae, bacterial vaginosis associated bacteria-2, Gardnerella spp., Mobiluncus curtisii, Mo. mulieris, Mycoplasma hominis, Ureaplasma urealyticum, Prevotella bivia, Megasphaera 1, and Megasphaera 2 in their vaginal sample. Fewer pregnant women with BV share Lactobacillus crispatus, L. gasseri, L. jensenii, and Enterococcus faecalis in their vaginal sample (P < 0.001). Classification and regression tree analysis was performed to determine which combinations of detected bacteria optimally diagnose BV in this population. A set of only four bacteria of 34 microorganisms (A. vaginae, Gardnerella spp., L. crispatus, and P. bivia) was the best combination to identify BV in a cohort of asymptomatic pregnant women, with a sensitivity of 77.1%, and specificity of 97.0% compared with the Nugent score. The quantitative PCR in the present study responds to the limits of the Nugent score by implementing an easily reproducible quantitative assay to assess the absence of BV in pregnancy., (Copyright © 2021 Association for Molecular Pathology and American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

This study aimed to analyse the frequency of occurrence of spontaneous decolonization in intensive care unit patients colonized by extended-spectrum beta-lactamase-producing Enterobacterales (ESBL-E) in order to assess the added value of continuing weekly ESBL-E rectal carriage screening in these patients. In total, 49,468 weekly rectal screening samples taken from 20,846 patients over 12 years were included. Among the 4280 ESBL-E carriers, only 109 patients (2.5%) could be considered decolonized at the end of their hospitalization with at least three consecutive negative samples. Overall, 7957 samples (16.1%) were requested for patients already identified as ESBL-E carriers. Avoiding unnecessary weekly screening following positive ESBL-E colonization results could decrease nursing and laboratory work loads., (Copyright © 2020 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.)

Background: Hypercoagulability seems to contribute to SARS-CoV-2 pneumonia pathogenesis. However, age and metabolic syndrome are potential confounders when assessing the value of coagulation biomarkers' prediction of COVID-19 outcomes. We assessed whether coagulation biomarkers, including factor VIII (FVIII) and von Willebrand factor (VWF) levels, measured at time of admission, were predictive of COVID-19 adverse outcomes irrespective of age and major comorbidities associated with metabolic syndrome., Methods: Blood was sampled at admission in 243 adult COVID-19 patients for analysis of coagulation biomarkers including FVIII and VWF on platelet-poor plasma. The association between baseline C-reactive protein (CRP), activated partial thromboplastin time ratio, prothrombin time ratio, D-dimers, fibrinogen, FVIII, VWF antigen (VWF:Ag), and FVIII/VWF:Ag ratio levels and adverse outcomes (increased oxygen requirements, thrombosis, and death at day 30) was assessed by regression analysis after adjustment on age, sex, body mass index (BMI), diabetes, and hypertension., Results: In univariable regression analysis increased CRP (subdistribution hazard ratio [SHR], 1.68; 95% confidence interval [CI], 1.26-2.23), increased fibrinogen (SHR, 1.32; 95% CI, 1.04-1.68), and decreased FVIII/VWF:Ag ratio (SHR, 0.70; 95% CI, 0.52-0.96) levels at admission were significantly associated with the risk of increased oxygen requirement during follow-up. Leucocytes (SHR, 1.36; 95% CI, 1.04-1.76), platelets (SHR,1.71; 95% CI, 1.11-2.62), D-dimers (SHR, 2.48; 95% CI, 1.66-3.78), and FVIII (SHR, 1.78; 95% CI, 1.17-2.68) were associated with early onset of thrombosis after admission. After adjustment for age, sex, BMI, hypertension, and diabetes, these associations were not modified., Conclusion: Coagulation biomarkers are early and independent predictors of increased oxygen requirement in COVID-19 patients., (© 2020 International Society on Thrombosis and Haemostasis.)

Purpose: Gastric leak occurs after sleeve gastrectomy (SG) in 2% of cases. Most staple-line disruptions (SLD) can be successfully treated with first-line endoscopic procedures. Less favorable situations may lead to more complex therapeutic strategies, like conversion to Roux-en-Y gastric bypass (RYGBP). The aim of our study is to predict the factors of endoscopic treatment failure and to assess the safety of conversion to RYGBP., Methods: We included all patients treated in two centers of academic excellence (n = 100) between 2013 and 2017 who had a malignant SLD after SG. A "malignant" leakage met one of the following poor prognosis criteria suggested in the literature: unsuccessfully treated by the first-line endoscopic treatment; generalized peritonitis; anatomical anomalies; gastro-cutaneous or gastro-pleural fistula (GCF/GPF); or chronic leaks (> 4 weeks)., Results: No deaths occurred during the follow-up (20 ± 12 months). The endoscopy reported an anatomically abnormal gastric tube in 35 (35%) patients (stenosis [n = 21 (21%)], twist [n = 9 (9%)], or both [n = 5 (5%)]). We could maintain the SG in place in 92% of cases without stenosis, twist, or GCF/GPF. Conversion to RYGBP due to leakage was necessary in 37 (37%) patients. Stenosis, twist, or GCF/GPF significantly prevented healing in multivariate analysis (respectively: p = 0.020, OR = 0.17, and p < 0.001, OR = 0.07-logistic regression)., Conclusion: Endoscopy is the treatment of choice for the management of chronic leaks after SG. The association of anatomical anomalies and GCF/GPF should lead to consideration of conversion to RYGBP.

Background: Gut dysbiosis due to the adverse effects of antibiotics affects outcomes of lung infection. Previous murine models relied on significant depletion of both gut and lung microbiota, rendering the analysis of immune gut-lung cross-talk difficult. Here, we study the effects of antibiotic-induced gut dysbiosis without lung dysbiosis on lung immunity and the consequences on acute P. aeruginosa lung infection., Methods: C57BL6 mice received 7 days oral vancomycin-colistin, followed by normal regimen or fecal microbial transplant or Fms-related tyrosine kinase 3 ligand (Flt3-Ligand) over 2 days, and then intra-nasal P. aeruginosa strain PAO1. Gut and lung microbiota were studied by next-generation sequencing, and lung infection outcomes were studied at 24 h. Effects of vancomycin-colistin on underlying immunity and bone marrow progenitors were studied in uninfected mice by flow cytometry in the lung, spleen, and bone marrow., Results: Vancomycin-colistin administration induces widespread cellular immunosuppression in both the lung and spleen, decreases circulating hematopoietic cytokine Flt3-Ligand, and depresses dendritic cell bone marrow progenitors leading to worsening of P. aeruginosa lung infection outcomes (bacterial loads, lung injury, and survival). Reversal of these effects by fecal microbial transplant shows that these alterations are related to gut dysbiosis. Recombinant Flt3-Ligand reverses the effects of antibiotics on subsequent lung infection., Conclusions: These results show that gut dysbiosis strongly impairs monocyte/dendritic progenitors and lung immunity, worsening outcomes of P. aeruginosa lung infection. Treatment with a fecal microbial transplant or immune stimulation by Flt3-Ligand both restore lung cellular responses to and outcomes of P. aeruginosa following antibiotic-induced gut dysbiosis.

Clostridium spp. are recovered from 25% of the blood culture positive with anaerobes. However, the clinical relevance of Clostridium bacteremia has been controverted in the literature, particularly for C. perfringens. We aimed to evaluate the clinical relevance of Clostridium bacteremia, either due to C. perfringens or other Clostridium species, and to identify the risk factors of mortality in these patients. A retrospective cohort study was conducted from January 2010 to April 2018. All the patients with at least one blood culture positive with any Clostridium species were included. Eighty-one patients with a least one blood culture positive with any Clostridium species were included. Seventy patients (86.4%) fulfilled the criteria for clinically relevant bacteremia. Bacteremia due to C. perfringens tended to be less clinically relevant than other Clostridium species but this was not statistically significant (76% vs 91.2%, P = 0.09). In case of clinically relevant bacteremia, the 30-day mortality rate was 31.4%. In multivariate analysis, adequate empiric antimicrobial therapy was significantly associated with survival (P = 0.03). In conclusion, bacteremia due to C. perfringens or other Clostridium species is usually clinically relevant. This finding was also supported by an improved survival at 30 days when adequate empiric antimicrobial therapy was administered., Competing Interests: Declaration of competing interest No conflict of interest., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Objective: The study aimed to evaluate the impact of the single nucleotide polymorphism (SNP) rs7903146 on the transcription factor 7-like 2 (TCF7L2) gene in stress-related hyperglycaemia (SRH), defined as blood glucose≥11mmol/L in at least two blood samples during the first 3 days in the intensive care unit (ICU), and on 28-day and 1-year mortality, and incidence of type 2 diabetes (T2D) at 6 months and 1 year in patients hospitalized in the ICU., Methods: This prospective observational (non-interventional) multicentre READIAB study, carried out during 2012-2016 in six French ICUs, involved adult patients admitted to ICUs for at least two organ failures; patients admitted for<48h were excluded. During the 3-day ICU observational period, genetic testing, blood glucose values and insulin treatment were recorded., Main Results: The association of rs7903146 with SRH was assessed using logistic regression models. Cox proportional hazards regression models assessed the associations between rs7903146 and mortality and between SRH and mortality, both at 28 days and 1 year. A total of 991 of the 1000 enrolled patients were included in the READIAB-G4 cohort, but 242 (24.4%) had preexisting diabetes and were excluded from the analyses. SRH occurred within the first 3 days in the ICU for one-third of the non-diabetes patients. The association between the rs7903146 polymorphism and SRH did not reach significance (P=0.078): OR (per one T copy) : 1.24, 95% CI: 0.98-1.58. A significant association was found between rs7903146 and 28-day mortality after adjusting for severity scores (P=0.026), but was no longer significant at 1 year (P=0.61). At 28 days, mortality was increased in patients with SRH (HR: 2.09, 95% CI: 1.43-3.06; P<0.001), and remained significant at 1 year after adjusting for severity scores (HR: 1.73, 95% CI: 1.32-2.28; P<0.001). On admission, non-diabetes patients with SRH had a higher incidence of T2D at 6 months vs. those without SRH (16.0% vs. 7.6%, RR: 2.11, 95% CI: 1.07-4.20; P=0.030). At 1 year, these figures were 13.4% vs. 9.2%, RR: 1.45, 95% CI: 0.71-2.96; P=0.31). Moreover, the rs7903146 polymorphism was not significantly associated with T2D development at either 6 months (P=0.72) or 1 year (P=0.64)., Conclusion: This study failed to demonstrate any significant association between rs7903146 and SRH. Nevertheless, the issue remains an important challenge, as SRH may be associated with increased rates of both mortality and T2D development., (Copyright © 2019. Published by Elsevier Masson SAS.)

Clostridium ventriculi (formerly Sarcina ventriculi) is a Gram-positive, obligate anaerobic coccus. Human infections due to this bacterium have rarely been reported, its involvement in the development of gastric ulcers and perforation has been suggested. We present a case of bacteremia due to C. ventriculi following acute colonic pseudo-obstruction., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Importance: Keeping a diary for patients while they are in the intensive care unit (ICU) might reduce their posttraumatic stress disorder (PTSD) symptoms., Objectives: To assess the effect of an ICU diary on the psychological consequences of an ICU hospitalization., Design, Setting, and Participants: Assessor-blinded, multicenter, randomized clinical trial in 35 French ICUs from October 2015 to January 2017, with follow-up until July 2017. Among 2631 approached patients, 709 adult patients (with 1 family member each) who received mechanical ventilation within 48 hours after ICU admission for at least 2 days were eligible, 657 were randomized, and 339 were assessed 3 months after ICU discharge., Interventions: Patients in the intervention group (n = 355) had an ICU diary filled in by clinicians and family members. Patients in the control group (n = 354) had usual ICU care without an ICU diary., Main Outcomes and Measures: The primary outcome was significant PTSD symptoms, defined as an Impact Event Scale-Revised (IES-R) score greater than 22 (range, 0-88; a higher score indicates more severe symptoms), measured in patients 3 months after ICU discharge. Secondary outcomes, also measured at 3 months and compared between groups, included significant PTSD symptoms in family members; significant anxiety and depression symptoms in patients and family members, based on a Hospital Anxiety and Depression Scale score greater than 8 for each subscale (range, 0-42; higher scores indicate more severe symptoms; minimal clinically important difference, 2.5); and patient memories of the ICU stay, reported with the ICU memory tool., Results: Among 657 patients who were randomized (median [interquartile range] age, 62 [51-70] years; 126 women [37.2%]), 339 (51.6%) completed the trial. At 3 months, significant PTSD symptoms were reported by 49 of 164 patients (29.9%) in the intervention group vs 60 of 175 (34.3%) in the control group (risk difference, -4% [95% CI, -15% to 6%]; P = .39). The median (interquartile range) IES-R score was 12 (5-25) in the intervention group vs 13 (6-27) in the control group (difference, -1.47 [95% CI, -1.93 to 4.87]; P = .38). There were no significant differences in any of the 6 prespecified comparative secondary outcomes., Conclusions and Relevance: Among patients who received mechanical ventilation in the ICU, the use of an ICU diary filled in by clinicians and family members did not significantly reduce the number of patients who reported significant PTSD symptoms at 3 months. These findings do not support the use of ICU diaries for preventing PTSD symptoms., Trial Registration: ClinicalTrials.gov Identifier: NCT02519725.

Background: Bacterial resistance to antibiotics is a daily concern in intensive care units. However, few data are available concerning the clinical consequences of in-vitro-defined resistance., Aim: To compare the mortality of patients with nosocomial infections according to bacterial resistance profiles., Methods: The prospective surveillance registry in 29 French intensive care units (ICUs) participating during the years 2000-2013 was retrospectively analysed. All patients presenting with a nosocomial infection in ICU were included., Findings: The registry contained 88,000 eligible patients, including 10,001 patients with a nosocomial infection. Among them, 3092 (36.7%) were related to resistant micro-organisms. Gram-negative bacilli exhibited the highest rate of resistance compared to Gram-positive cocci (52.8% vs 48.1%; P < 0.001). In-hospital mortality was higher in cases of patients with antibiotic-resistant infectious agents (51.9% vs 45.5%; P < 0.001), and critical care length of stay was longer (33 ± 26 vs 29 ± 22 days; P < 0.001). These results remained significant after SAPS II matching (P < 0.001) and in the Gram-negative bacilli and Gram-positive cocci subgroups. No difference in mortality was found with respect to origin prior to admission., Conclusion: Patients with bacterial resistance had higher ICU mortality and increased length of stay, regardless of the bacterial species or origin of the patient., (Copyright © 2019 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.)

While antibiotic use is a risk factor of carbapenemase-producing Enterobacteriaceae (CPE) acquisition, the importance of timing of antibiotic administration relative to CPE exposure remains unclear. In a murine model of gut colonization by New Delhi metallo-beta-lactamase-1 (NDM-1)-producing Klebsiella pneumoniae , a single injection of clindamycin within at most 1 week before or after CPE exposure induced colonization persisting up to 100 days. The timing of antibiotic administration relative to CPE exposure may be relevant to infection control and antimicrobial stewardship approaches., (Copyright © 2019 American Society for Microbiology.)

Objective: Pelvic fractures represent 5% of all traumatic fractures and 30% are isolated pelvic fractures. Pelvic fractures are found in 10 to 20% of severe trauma patients and their presence is highly correlated to increasing trauma severity scores. The high mortality of pelvic trauma, about 8 to 15%, is related to actively bleeding pelvic injuries and/or associated injuries to the head, abdomen or chest. Regardless of the severity of pelvic trauma, diagnosis and treatment must proceed according to a strategy that does not delay the management of the most severely injured patients. To date, in France, there are no guidelines issued by healthcare authorities or professional societies that address this subject., Design: A consensus committee of 22 experts from the French Society of Anaesthesia and Intensive Care Medicine (Société Française d'Anesthésie et de Réanimation; SFAR) and the French Society of Emergency Medicine (Société Française de Médecine d'Urgence; SFMU) in collaboration with the French Society of Radiology (Société Française de Radiologie; SFR), French Defence Health Service (Service de Santé des Armées; SSA), French Society of Urology (Association Française d'Urologie; AFU), the French Society of Orthopaedic and Trauma Surgery (Société Française de Chirurgie Orthopédique et Traumatologique; SOCFCOT), and the French Society of Digestive Surgery (Société Française de Chirurgie digestive; SFCD) was convened. A formal conflict-of-interest (COI) policy was developed at the onset of the process and enforced throughout. The entire guidelines process was conducted independently from any industry funding. The authors were advised to follow the principles of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system to guide assessment of quality of evidence. The potential drawbacks of making strong recommendations in the presence of low-quality evidence were emphasised., Methods: Population, intervention, comparison, and outcomes (PICO) questions were reviewed and updated as needed, and evidence profiles were generated. The analysis of the literature and the recommendations were then conducted according to the GRADE ® methodology., Results: The SFAR Guideline panel provided 22 statements on prehospital and hospital management of the unstable patient with pelvic fracture. After three rounds of discussion and various amendments, a strong agreement was reached for 100% of recommendations. Of these recommendations, 11 have a high level of evidence (Grade 1 ± ), 11 have a low level of evidence (Grade 2 ± )., Conclusions: Substantial agreement exists among experts regarding many strong recommendations for management of the unstable patient with pelvic fracture., (Copyright © 2018 The Author(s). Published by Elsevier Masson SAS.. All rights reserved.)

Background: Rapid identification and treatment of tissue hypoxia reaching anaerobiosis (dysoxia) may reduce organ failure and the occurrence of major postoperative complications (MPC) after cardiac surgery. The predictive ability of PCO2-based dysoxia biomarkers, central venous-to-arterial PCO2 difference (ΔPCO2) and ΔPCO2 to arteriovenous oxygen content difference ratio, is poorly studied in this setting., Objectives: We evaluated the ability of PCO2-based tissue dysoxia biomarkers, blood lactate concentration and central venous oxygen saturation measured 2 h after admission to the ICU as predictors of MPC., Design: A prospective, observational cohort study., Setting: Single-centre, academic hospital cardiovascular ICU., Patients: We included adult patients undergoing cardiac surgery with cardiopulmonary bypass and measured dysoxia biomarkers at ICU admission, and after 2, 6 and 24 h., Main Outcome Measures: The primary endpoint was MPC, a composite of cardiac and noncardiac MPC evaluated in the 48 h following surgery. After univariate analysis of MPC covariates including dysoxia biomarkers measured at 2 h, multivariate logistic regression analyses were performed to identify the association of these biomarkers with MPC for confounders. Areas under the receiver operating characteristic curves were determined for biomarkers which remained independently associated with MPC., Results: MPC occurred in 56.5% of the 308 patients analysed. ΔPCO2, blood lactate concentration and central venous oxygen saturation measured at 2 h, but not ΔPCO2 to arteriovenous oxygen content difference ratio, were significantly associated with MPC. However, only ΔPCO2 was independently associated with MPC after multivariate analysis. The areas under the receiver operating characteristic curves of ΔPCO2 measured at 2 h for MPC prediction was 0.64 (95% CI 0.57 to 0.70, P < 0.001)., Conclusion: After cardiac surgery with cardiopulmonary bypass, ΔPCO2 measured 2 h after ICU admission was the only dysoxia biomarker independently associated with MPC, but with limited performance., Trial Registration: ClinicalTrials.gov, NCT03107572.

The massive consumption of antibiotics in the ICU is responsible for substantial ecological side effects that promote the dissemination of multidrug-resistant bacteria (MDRB) in this environment. Strikingly, up to half of ICU patients receiving empirical antibiotic therapy have no definitively confirmed infection, while de-escalation and shortened treatment duration are insufficiently considered in those with documented sepsis, highlighting the potential benefit of implementing antibiotic stewardship programs (ASP) and other quality improvement initiatives. The objective of this narrative review is to summarize the available evidence, emerging options, and unsolved controversies for the optimization of antibiotic therapy in the ICU. Published data notably support the need for better identification of patients at risk of MDRB infection, more accurate diagnostic tools enabling a rule-in/rule-out approach for bacterial sepsis, an individualized reasoning for the selection of single-drug or combination empirical regimen, the use of adequate dosing and administration schemes to ensure the attainment of pharmacokinetics/pharmacodynamics targets, concomitant source control when appropriate, and a systematic reappraisal of initial therapy in an attempt to minimize collateral damage on commensal ecosystems through de-escalation and treatment-shortening whenever conceivable. This narrative review also aims at compiling arguments for the elaboration of actionable ASP in the ICU, including improved patient outcomes and a reduction in antibiotic-related selection pressure that may help to control the dissemination of MDRB in this healthcare setting.

Tetraphenylethylene (TPE) is fluorescent through aggregation induced emission (AIE) in water. Herein, TPE was used as the core of glycoclusters that target the bacterial lectins LecA and LecB of Pseudomonas aeruginosa. Synthesis of these TPE-based glycoclusters was accomplished by using azide-alkyne "click" chemistry. The AIE properties of the resulting glycoclusters could be readily verified, but imaging could not be pursued due to the overlap of the fluorescence signals from cells and bacteria. Nonetheless, the glycoclusters displayed nanomolar affinities toward LecA and LecB. Further evaluation in a cell-based anti-adhesive assay highlighted a limited decrease in adhesion (20%) for the fucosylated glycocluster. This confirmed that these TPE-based glycoclusters are indeed LecA and LecB high-affinity ligands. Nevertheless, the hypotheses involving their application in imaging or anti-adhesive therapy could not be verified.

Background: Preterm delivery during pregnancy (<37 weeks' gestation) is a leading cause of perinatal mortality and morbidity. Treating bacterial vaginosis during pregnancy can reduce poor outcomes, such as preterm birth. We aimed to investigate whether treatment of bacterial vaginosis decreases late miscarriages or spontaneous very preterm birth., Methods: PREMEVA was a double-blind randomised controlled trial done in 40 French centres. Women aged 18 years or older with bacterial vaginosis and low-risk pregnancy were eligible for inclusion and were randomly assigned (2:1) to three parallel groups: single-course or triple-course 300 mg clindamycin twice-daily for 4 days, or placebo. Women with high-risk pregnancy outcomes were eligible for inclusion in a high-risk subtrial and were randomly assigned (1:1) to either single-course or triple-course clindamycin. The primary outcome was a composite of late miscarriage (16-21 weeks) or spontaneous very preterm birth (22-32 weeks), which we assessed in all patients with delivery data (modified intention to treat). Adverse events were systematically reported. This study is registered with ClinicalTrials.gov, number NCT00642980., Findings: Between April 1, 2006, and June 30, 2011, we screened 84 530 pregnant women before 14 weeks' gestation. 5630 had bacterial vaginosis, of whom 3105 were randomly assigned to groups in the low-risk trial (n=943 to receive single-course clindamycin, n=968 to receive triple-course clindamycin, and n=958 to receive placebo) or high-risk subtrial (n=122 to receive single-course clindamycin and n=114 to receive triple-course clindamycin). In 2869 low-risk pregnancies, the primary outcome occurred in 22 (1·2%) of 1904 participants receiving clindamycin and 10 (1·0%) of 956 participants receiving placebo (relative risk [RR] 1·10, 95% CI 0·53-2·32; p=0·82). In 236 high-risk pregnancies, the primary outcome occurred in 5 (4·4%) participants in the triple-course clindamycin group and 8 (6·0%) participants in the single-course clindamycin group (RR 0·67, 95% CI 0·23-2·00; p=0·47). In the low-risk trial, adverse events were more common in the clindamycin groups than in the placebo group (58 [3·0%] of 1904 vs 12 [1·3%] of 956; p=0·0035). The most commonly reported adverse event was diarrhoea (30 [1·6%] in the clindamycin groups vs 4 [0·4%] in the placebo group; p=0·0071); abdominal pain was also observed in the clindamycin groups (9 [0·6%] participants) versus none in the placebo group (p=0·034). No severe adverse event was reported in any group. Adverse fetal and neonatal outcomes did not differ significantly between groups in the high-risk subtrial., Interpretation: Systematic screening and subsequent treatment for bacterial vaginosis in women with low-risk pregnancies shows no evidence of risk reduction of late miscarriage or spontaneous very preterm birth. Use of antibiotics to prevent preterm delivery in this patient population should be reconsidered., Funding: French Ministry of Health., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: The French Society of Anaesthesia and Intensive Care Medicine and the French Society of Intensive Care edited guidelines focused on hospital-acquired pneumonia (HAP) in intensive care unit. The goal of 16 French-speaking experts was to produce a framework enabling an easier decision-making process for intensivists., Results: The guidelines were related to 3 specific areas related to HAP (prevention, diagnosis and treatment) in 4 identified patient populations (COPD, neutropenia, post-operative and paediatric). The literature analysis and the formulation of the guidelines were conducted according to the Grade of Recommendation Assessment, Development and Evaluation methodology. An extensive literature research over the last 10 years was conducted based on publications indexed in PubMed™ and Cochrane™ databases., Conclusions: HAP should be prevented by a standardised multimodal approach and the use of selective digestive decontamination in units where multidrug-resistant bacteria prevalence was below 20%. Diagnosis relies on clinical assessment and microbiological findings. Monotherapy, in the absence of risk factors for multidrug-resistant bacteria, non-fermenting Gram-negative bacilli and/or increased mortality (septic shock, organ failure), is strongly recommended. After microbiological documentation, it is recommended to reduce the spectrum and to prefer monotherapy for the antibiotic therapy of HAP, including for non-fermenting Gram-negative bacilli.

Background and Aims: The potential benefit of the centralization of Bariatric surgery (BS) remains debated. The aim of this study was to evaluate the impact on 90-day mortality of an innovative organization aiming at centralizing the care of severe postoperative complications of BS., Study Design: The centralization of care for postoperative complication after BS was implemented by French Authorities in 2013 in the Nord-Pas-de-Calais Region, France. This unique formalized network (OSEAN), coordinated by 1 tertiary referral center, enrolled all regional institutions performing bariatric surgery. Data were extracted from the medico-administrative database providing information on all patients undergoing BS between 2009 and 2016 in OSEAN (n = 22,928) and in Rest of France (n = 288,942). The primary outcome was the evolution of 90-day mortality before and after the implementation of this policy. Rest of France was used as a control group to adjust the results to improvement with time of BS outcomes., Results: The numbers of primary procedure and reoperations increased similarly before and after 2013 within OSEAN and in Rest of France. The 90-day mortality rate became significantly lower within OSEAN than in the rest of France after 2013 (0.03% vs 0.08%, P < 0.01). This difference was confirmed in multivariate analysis after adjustment to the procedure specific mortality (P < 0.04). The reduction of 90-day mortality was most visible for sleeve gastrectomy., Conclusion: The implementation of centralized care for early postoperative complications after BS in OSEAN was associated with reduced 90-day mortality. Our results indicate that this reduction was not due to a lower incidence of complications but to the improvement of their management.

Pseudomonas aeruginosa infections are challenging due to intrinsic and acquired resistance mechanisms. We report here the draft genome sequences of two multidrug-resistant strains-PAL0.1, isolated from the airways of an intensive care unit (ICU) patient with ventilator-associated pneumonia, and PAL1.1, isolated from blood cultures of an ICU patient with sepsis.

Carbapenemase-producing Klebsiella pneumoniae represents an emerging public health issue. Here, we present the draft whole-genome sequences of K. pneumoniae clinical strains KPL0.1 (OXA-48 carbapenemase) and KPL0.2 (NDM-1 carbapenemase). These genome sequences should help in investigating pathophysiological mechanisms of digestive colonization or infection with these highly resistant bacteria.

Trauma remains a leading cause of death worldwide. Hemorrhagic shock and direct injury to vital organs are responsible for early mortality whereas most delayed deaths are secondary to complex pathophysiological processes. These processes result from imbalanced systemic reactions to the multiple aggressions associated with trauma. Trauma results in the uncontrolled local and systemic release of endogenous mediators acting as danger signals [damage-associated molecular patterns (DAMPs)]. Their recognition by the innate immune system triggers a pro-inflammatory immune response paradoxically associated with concomitant immunosuppression. These responses, ranging in intensity from inappropriate to overwhelming, promote the propagation of injuries to remote organs, leading to multiple organ failure and death. Some of the numerous DAMPs released after trauma trigger the assembly of intracellular multiprotein complexes named inflammasomes. Once activated by a ligand, inflammasomes lead to the activation of a caspase. Activated caspases allow the release of mature forms of interleukin-1β and interleukin-18 and trigger a specific pro-inflammatory cell death termed pyroptosis. Accumulating data suggest that inflammasomes, mainly NLRP3, NLRP1, and AIM2, are involved in the generation of tissue damage and immune dysfunction after trauma. Following trauma-induced DAMP(s) recognition, inflammasomes participate in multiple ways in the development of exaggerated systemic and organ-specific inflammatory response, contributing to organ damage. Inflammasomes are involved in the innate responses to traumatic brain injury and contribute to the development of acute respiratory distress syndrome. Inflammasomes may also play a role in post-trauma immunosuppression mediated by dysregulated monocyte functions. Characterizing the involvement of inflammasomes in the pathogenesis of post-trauma syndrome is a key issue as they may be potential therapeutic targets. This review summarizes the current knowledge on the roles of inflammasomes in trauma.