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Abstract Intra-abdominal infections (IAIs) are an important cause of morbidity and mortality in hospital settings worldwide. The cornerstones of IAI management include rapid, accurate diagnostics; timely, adequate source control; appropriate, short-duration antimicrobial therapy administered according to the principles of pharmacokinetics/pharmacodynamics and antimicrobial stewardship; and hemodynamic and organ functional support with intravenous fluid and adjunctive vasopressor agents for critical illness (sepsis/organ dysfunction or septic shock after correction of hypovolemia). In patients with IAIs, a personalized approach is crucial to optimize outcomes and should be based on multiple aspects that require careful clinical assessment. The anatomic extent of infection, the presumed pathogens involved and risk factors for antimicrobial resistance, the origin and extent of the infection, the patient’s clinical condition, and the host’s immune status should be assessed continuously to optimize the management of patients with complicated IAIs.

Night work is frequently associated with sleep deprivation and is associated with greater surgical and medical complications. Lung transplantation (LT) is carried out both at night and during the day and involves many medical healthcare workers. The goal of the study was to compare morbidity and mortality between LT recipients according to LT operative time. We performed a retrospective, observational, single-center study. When the procedure started between 6 AM and 6 PM, the patient was allocated to the Daytime group. If the procedure started between 6 PM and 6 AM, the patient was allocated to the Nighttime group. Between January 2015 and December 2020, 253 patients were included. A total of 168 (66%) patients were classified into the Day group, and 85 (34%) patients were classified into the Night group. Lung Donors’ general characteristics were similar between the groups. The 90-day and one-year mortality rates were similar between the groups (90-days: n = 13 (15%) vs. n = 26 (15%), p = 0.970; 1 year: n = 18 (21%) vs. n = 42 (25%), p = 0.499). Daytime LT was associated with more one-year airway dehiscence (n = 36 (21%) vs. n = 6 (7.1%), p = 0.004). In conclusion, among patients who underwent LT, there was no significant association between operative time and survival.

IntroductionAlthough many studies have underscored the importance of T cells, phenotypically and functionally, fewer have studied the functions of myeloid cells in COVID disease. In particular, the potential role of myeloid cells such as monocytes and low-density neutrophils (LDNs) in innate responses and particular in the defense against secondary bacterial infections has been much less documented.MethodsHere, we compared, in a longitudinal study, healthy subjects, idiopathic fibrosis patients, COVID patients who were either hospitalized/moderate (M-) or admitted to ICU (COV-ICU) and patients in ICU hospitalized for other reasons (non-COV-ICU).ResultsWe show that COVID patients have an increased proportion of low-density neutrophils (LDNs), which produce high levels of proteases (particularly, NE, MMP-8 and MMP-9) (unlike non-COV-ICU patients), which are partly responsible for causing type II alveolar cell damage in co-culture experiments. In addition, we showed that M- and ICU-COVID monocytes had reduced responsiveness towards further live Pseudomonas aeruginosa (PAO1 strain) infection, an important pathogen colonizing COVID patients in ICU, as assessed by an impaired secretion of myeloid cytokines (IL-1, TNF, IL-8,…). By contrast, lymphoid cytokines (in particular type 2/type 3) levels remained high, both basally and post PAO1 infection, as reflected by the unimpaired capacity of T cells to proliferate, when stimulated with anti-CD3/CD28 beads.DiscussionOverall, our results demonstrate that COVID circulatory T cells have a biased type 2/3 phenotype, unconducive to proper anti-viral responses and that myeloid cells have a dual deleterious phenotype, through their LDN-mediated damaging effect on alveolar cells and their impaired responsiveness (monocyte-mediated) towards bacterial pathogens such as P. aeruginosa.

Background: The AbSeS-classification defines specific phenotypes of patients with intra-abdominal infection based on the (1) setting of infection onset (community-acquired, early onset, or late-onset hospital-acquired), (2) presence or absence of either localized or diffuse peritonitis, and (3) severity of disease expression (infection, sepsis, or septic shock). This classification system demonstrated reliable risk stratification in intensive care unit (ICU) patients with intra-abdominal infection. This study aimed to describe the epidemiology of ICU patients with pancreatic infection and assess the relationship between the components of the AbSeS-classification and mortality. Methods: This was a secondary analysis of an international observational study (“AbSeS”) investigating ICU patients with intra-abdominal infection. Only patients with pancreatic infection were included in this analysis (n=165). Mortality was defined as ICU mortality within 28 days of observation for patients discharged earlier from the ICU. Relationships with mortality were assessed using logistic regression analysis and reported as odds ratio (OR) and 95% confidence interval (CI). Results: The overall mortality was 35.2% (n=58). The independent risk factors for mortality included older age (OR=1.03, 95% CI: 1.0 to 1.1 P=0.023), localized peritonitis (OR=4.4, 95% CI: 1.4 to 13.9 P=0.011), and persistent signs of inflammation at day 7 (OR=9.5, 95% CI: 3.8 to 23.9, P

Abstract Background Temporal changes in the microbiological resistance profile have been reported in several life-threatening infections. However, no data have ever assessed this issue in postoperative peritonitis (POP). Our purpose was to assess the rate of multidrug-resistant organisms (MDROs) in POP over a two-decade period and to analyse their influence on the adequacy of empirical antibiotic therapy (EAT). Methods This retrospective monocentric analysis (1999–2019) addressed the changes over time in microbiologic data, including the emergence of MDROs and the adequacy of EAT for all intensive care unit adult patients treated for POP. The in vitro activities of 10 antibiotics were assessed to determine the most adequate EAT in the largest number of cases among 17 antibiotic regimens in patients with/without MDRO isolates. Our primary endpoint was to determine the frequency of MDRO and their temporal changes. Our second endpoint assessed the impact of MDROs on the adequacy of EAT per patient and their temporal changes based on susceptibility testing. In this analysis, the subgroup of patients with MDRO was compared with the subgroup of patients free of MDRO. Results A total of 1,318 microorganisms were cultured from 422 patients, including 188 (45%) patients harbouring MDROs. The growing proportions of MDR Enterobacterales were observed over time (p = 0.016), including ESBL-producing strains (p = 0.0013), mainly related to Klebsiella spp (p

Introduction Lung transplantation (LTx) aims at improving survival and quality of life for patients with end-stage lung diseases. Venoarterial extracorporeal membrane oxygenation (VA-ECMO) is used as intraoperative support for LTx, despite no precise guidelines for its initiation. We aim to evaluate two strategies of VA-ECMO initiation in the perioperative period in patients with obstructive or restrictive lung disease requiring bilateral LTx. In the control ‘on-demand’ arm, high haemodynamic and respiratory needs will dictate VA-ECMO initiation; in the experimental ‘systematic’ arm, VA-ECMO will be pre-emptively initiated. We hypothesise a ‘systematic’ strategy will increase the number of ventilatory-free days at day 28.Methods and analysis We designed a multicentre randomised controlled trial in parallel groups. Adult patients with obstructive or restrictive lung disease requiring bilateral LTx, without a formal indication for pre-emptive VA-ECMO before LTx, will be included. Patients with preoperative pulmonary hypertension with haemodynamic collapse, ECMO as a bridge to transplantation, severe hypoxaemia or hypercarbia will be secondarily excluded. In the systematic group, VA-ECMO will be systematically implanted before the first pulmonary artery cross-clamp. In the on-demand group, VA-ECMO will be implanted intraoperatively if haemodynamic or respiratory indices meet preplanned criteria. Non-inclusion, secondary exclusion and VA-ECMO initiation criteria were validated by a Delphi process among investigators. Postoperative weaning of ECMO and mechanical ventilation will be managed according to best practice guidelines. The number of ventilator-free days at 28 days (primary endpoint) will be compared between the two groups in the intention-to-treat population. Secondary endpoints encompass organ failure occurrence, day 28, day 90 and year 1 vital status, and adverse events.Ethics and dissemination The sponsor is the Assistance Publique–Hôpitaux de Paris. The ECMOToP protocol version 2.1 was approved by Comité de Protection des Personnes Ile de France VIII. Results will be published in international peer-reviewed medical journals.Trial registration number NCT05664204.

Abstract Intra-abdominal infections (IAI) are among the most common global healthcare challenges and they are usually precipitated by disruption to the gastrointestinal (GI) tract. Their successful management typically requires intensive resource utilization, and despite the best therapies, morbidity and mortality remain high. One of the main issues required to appropriately treat IAI that differs from the other etiologies of sepsis is the frequent requirement to provide physical source control. Fortunately, dramatic advances have been made in this aspect of treatment. Historically, source control was left to surgeons only. With new technologies non-surgical less invasive interventional procedures have been introduced. Alternatively, in addition to formal surgery open abdomen techniques have long been proposed as aiding source control in severe intra-abdominal sepsis. It is ironic that while a lack or even delay regarding source control clearly associates with death, it is a concept that remains poorly described. For example, no conclusive definition of source control technique or even adequacy has been universally accepted. Practically, source control involves a complex definition encompassing several factors including the causative event, source of infection bacteria, local bacterial flora, patient condition, and his/her eventual comorbidities. With greater understanding of the systemic pathobiology of sepsis and the profound implications of the human microbiome, adequate source control is no longer only a surgical issue but one that requires a multidisciplinary, multimodality approach. Thus, while any breach in the GI tract must be controlled, source control should also attempt to control the generation and propagation of the systemic biomediators and dysbiotic influences on the microbiome that perpetuate multi-system organ failure and death. Given these increased complexities, the present paper represents the current opinions and recommendations for future research of the World Society of Emergency Surgery, of the Global Alliance for Infections in Surgery of Surgical Infection Society Europe and Surgical Infection Society America regarding the concepts and operational adequacy of source control in intra-abdominal infections.

BackgroundPerioperative anaphylaxis is a rare and acute systemic manifestation of drug-induced hypersensitivity reactions that occurs following anesthesia induction; the two main classes of drugs responsible for these reactions being neuromuscular blocking agents (NMBA) and antibiotics. The sensitization mechanisms to the drugs are not precisely known, and few risk factors have been described. A growing body of evidence underlines a link between occurrence of allergy and microbiota composition. However, no data exist on microbiota in perioperative anaphylaxis. The aim of this study was to compare circulating microbiota richness and composition between perioperative anaphylaxis patients and matched controls.MethodsCirculating 16s rDNA was quantified and sequenced in serum samples from 20 individuals with fully characterized IgE-mediated NMBA-related anaphylaxis and 20 controls matched on sex, age, NMBA received, type of surgery and infectious status. Microbiota composition was analyzed with a published bioinformatic pipeline and links with patients clinical and biological data investigated.ResultsAnalysis of microbiota diversity showed that anaphylaxis patients seem to have a richer circulating microbiota than controls, but no major differences of composition could be detected with global diversity indexes. Pairwise comparison showed a difference in relative abundance between patients and controls for Saprospiraceae, Enterobacteriaceae, Veillonellaceae, Escherichia-Shigella, Pseudarcicella, Rhodoferax, and Lewinella. Some taxa were associated with concentrations of mast cell tryptase and specific IgE.ConclusionWe did not find a global difference in terms of microbiota composition between anaphylaxis patient and controls. However, several taxa were associated with anaphylaxis patients and with their biological data. These findings must be further confirmed in different settings to broaden our understanding of drug anaphylaxis pathophysiology and identify predisposition markers.

Abstract Introduction Ceftazidime–avibactam has proven activity against multidrug-resistant (MDR) bacteria in clinical trials and real-world studies. This study was conducted to describe the patterns of use of ceftazidime–avibactam (including indications and associated antibiotics), and the effectiveness and safety of ceftazidime–avibactam in real-world clinical practice. Methods This non-interventional medical chart review study was conducted in 11 countries across the European and Latin American (LATAM) regions. Consecutive patients treated in clinical practice with at least one dose of ceftazidime–avibactam for an approved indication per country label since 01 January 2018 (or launch date in the country if posterior) were enrolled. Effectiveness analyses were conducted in patients treated with ceftazidime–avibactam for at least 72 h. Results Of the 569 eligible patients enrolled, 516 (90.7%) were treated for at least 72 h (354 patients from Europe and 162 patients from LATAM); 390 patients (75.7%) had switched from another antibiotic line for Gram-negative coverage. Infection sources were intra-abdominal, urinary, respiratory, bloodstream infections, and other infections (approximately 20% each). K. pneumoniae was the most common microorganism identified in the latest microbiological evaluation before starting ceftazidime–avibactam (59.3%). Two-thirds of microorganisms tested for susceptibility were MDR, of which 89.3% were carbapenem-resistant. The common MDR mechanisms for K. pneumoniae were carbapenemase (33.9%), oxacillinase 48 (25.2%), extended-spectrum beta-lactamase (21.5%), or metallo-beta-lactamase (14.2%) production. Without prior patient exposure, 17 isolates (mostly K. pneumoniae) were resistant to ceftazidime–avibactam. Treatment success was achieved in 77.3% of patients overall (88.3% among patients with urinary infection), regardless of first or second treatment line. In-hospital mortality rate was 23.1%. Adverse events were reported for six of the 569 patients enrolled. Conclusion This study provides important real-world evidence on treatment patterns, effectiveness, and safety of ceftazidime–avibactam in clinical practice through its recruitment in the European and LATAM regions. Ceftazidime–avibactam is one of the antibiotics to consider for treatment of MDR bacteria. Trial Registration ClinicalTrials.gov identifier, NCT03923426.

Abstract Background Airway complications are frequent after lung transplantation (LT), as they affect up to 23% of recipients. The implication of perioperative extracorporeal membrane oxygenation (ECMO) support and haemodynamic instability has never been specifically assessed. The first aim of this study was to explore the impact of perioperative ECMO support on bronchial anastomotic dehiscence (BAD) at Day 90 after LT. Methods This prospective observational monocentric study analysed BAD in all consecutive patients who underwent LT in the Bichat Claude Bernard Hospital, Paris, France, between January 2016 and May 2019. BAD visible on bronchial endoscopy and/or tomodensitometry was recorded. A univariate analysis was performed (Fisher’s exacts and Mann–Whitney tests), followed by a multivariate analysis to assess independent risk factors for BAD during the first 90 days after LT (p

Abstract Background Necrotizing skin and soft tissue infections (NSTIs) are rare but serious and rapidly progressive infections characterized by necrosis of subcutaneous tissue, fascia and even muscle. The care pathway of patients with NSTIs is poorly understood. A better characterization of the care trajectory of these patients and a better identification of patients at risk of a complicated evolution, requiring prolonged hospitalization, multiple surgical re-interventions, or readmission to the intensive care unit (ICU), is an essential prerequisite to improve their care. The main objective of this study is to obtain large-scale data on the care pathway of these patients. We performed a retrospective multicenter observational cohort study in 13 Great Paris area hospitals, including patients hospitalized between January 1, 2015 and December 31, 2019 in the ICU for surgically confirmed NSTIs. Results 170 patients were included. The median duration of stay in ICU and hospital was 8 (3–17) and 37 (14–71) days, respectively. The median time from admission to first surgical debridement was 1 (0–2) day but 69.9% of patients were re-operated with a median of 1 (0–3) additional debridement. Inter-hospital transfer was necessary in 52.4% of patients. 80.2% of patients developed organ failures during the course of ICU stay with 51.8% of patients requiring invasive mechanical ventilation, 77.2% needing vasopressor support and 27.7% renal replacement therapy. In-ICU and in-hospital mortality rates were 21.8% and 28.8%, respectively. There was no significant difference between patients with abdomino-perineal NSTIs (n = 33) and others (n = 137) in terms of in-hospital or ICU mortality. Yet, immunocompromised patients (n = 43) showed significantly higher ICU and in-hospital mortality rates than non-immunocompromised patients (n = 127) (37.2% vs. 16.5%, p = 0.009, and 53.5% vs. 20.5%, p

Abstract We evaluated the contribution of artificial intelligence in predicting the risk of acute cellular rejection (ACR) using early plasma levels of soluble CD31 (sCD31) in combination with recipient haematosis, which was measured by the ratio of arterial oxygen partial pressure to fractional oxygen inspired (PaO2/FiO2) and respiratory SOFA (Sequential Organ Failure Assessment) within 3 days of lung transplantation (LTx). CD31 is expressed on endothelial cells, leukocytes and platelets and acts as a “peace-maker” at the blood/vessel interface. Upon nonspecific activation, CD31 can be cleaved, released, and detected in the plasma (sCD31). The study included 40 lung transplant recipients, seven (17.5%) of whom experienced ACR. We modelled the plasma levels of sCD31 as a nonlinear dependent variable of the PaO2/FiO2 and respiratory SOFA over time using multivariate and multimodal models. A deep convolutional network classified the time series models of each individual associated with the risk of ACR to each individual in the cohort.

Abstract Background During the COVID-19 first wave in France, the capacity of intensive care unit (ICU) beds almost doubled, mainly because of the opening of temporary ICUs with staff and equipment from anaesthesia. Objectives We aim to investigate if the initial management in temporary ICU is associated with a change in ICU mortality and short-term prognosis. Design Retrospective single-centre cohort study. Setting Surgical ICU of the Bichat Claude Bernard University Hospital during the COVID-19 “first wave” (from 18 March to 10 April 2020). Patients All consecutive patients older than 18 years of age with laboratory-confirmed SARS-CoV-2 infection and/or typical radiological patterns were included during their first stay in the ICU for COVID-19. Intervention Patients were admitted to a temporary ICU if no room was available in the classical ICU and if they needed invasive mechanical ventilation but no renal replacement therapy or Extracorporeal Membrane Oxygenation (ECMO) in the short term. The temporary ICUs were managed by mixed teams (from the ICU and anaesthesiology departments) following a common protocol and staff meetings. Main outcome measure ICU mortality Results Among the 59 patients admitted, 37 (62.7%) patients had initial management in the temporary ICU. They had the same characteristics on admission and the same medical management as patients admitted to the classical ICU. ICU mortality was similar in the 2 groups (32.4% in temporary ICUs versus 40.9% in classical ICUs; p=0.58). SAPS-II and ECMO use were associated with mortality in multivariate analysis but not admission to the temporary ICU. Conclusion In an overload context of the ICU of a geographical area, our temporary ICU model allowed access to intensive care for all patients requiring it without endangering them.

Abstract Introduction The maximum gain in quality of life after lung transplantation (LT) is expected between six months and one year after LT, as the occurrence of chronic lung allograft dysfunction may mask the beneficial effects beyond one year. Thus, the postoperative period could be the cornerstone of graft success. We sought to describe the factors present before postoperative admission to the ICU and associated with favorable, arduous or fatal pathway within 90 days of LT. Materials and methods We conducted a retrospective single-center study between January 2015 and December 2020. Using multinomial regression, we assessed the demographic, preoperative and intraoperative characteristics of patients associated with favorable (duration of postoperative mechanical ventilation

BackgroundRisk factors and the incidence of prolonged mechanical ventilation (PMV) after lung transplantation (LT) have been poorly described. The study assessed predictive factors of PMV after LT.MethodsThis observational, retrospective, monocentric study included all patients who received LT in Bichat Claude Bernard Hospital between January 2016 and December 2020. PMV was defined as a duration of MV > 14 days. Independent risk factors for PMV were studied using multivariate analysis. One-year survival depending on PMV was studied using Kaplan Meier and log-rank tests. A p value 5 red blood cell units (p

Abstract Severe infections involving Panton-Valentine leukocidin-producing Staphylococcus aureus (PVL + Sa) are increasing. This monocentre, retrospective descriptive cohort assessed clinical characteristics and outcome of paediatric and adult patients admitted for community-acquired PVL + Sa infections to the unique intensive care unit (ICU) on New Caledonia Island. Overall, 72 patients (including 23 children) admitted for acute respiratory failure (42%), sepsis/septic shock (21%), and/or postoperative care (32%) were analysed. Most patients had pulmonary (64%), skin/soft tissue (SSTI) (54%) and/or osteoarticular (38%) infections. Multifocal infections (≥ 2 sites) and bacteraemia were reported in 65% and 76% of the patients, respectively. Methicillin-resistant S. aureus isolates were reported in 61% of adult cases versus 30% in children (p

Toxic shock syndrome (TSS) is a rare, life-threatening, toxin-mediated infectious process linked, in the vast majority of cases, to toxin-producing strains of Staphylococcus aureus or Streptococcus pyogenes. The pathophysiology, epidemiology, clinical presentation, microbiological features, management and outcome of TSS are described in this review. Bacterial superantigenic exotoxins induces unconventional polyclonal lymphocyte activation, which leads to rapid shock, multiple organ failure syndrome, and death. The main described superantigenic exotoxins are toxic shock syndrome toxin—1 (TSST-1) and enterotoxins for Staphylococcus aureus and Streptococcal pyrogenic exotoxins (SpE) A, B, and C and streptococcal superantigen A (SsA) for Streptococcus pyogenes. Staphylococcal TSS can be menstrual or nonmenstrual. Streptococcal TSS is linked to a severe group A streptococcal infection and, most frequently, to a necrotizing soft tissue infection. Management of TSS is a medical emergency and relies on early detection, immediate resuscitation, source control and eradication of toxin production, bactericidal antibiotic treatment, and protein synthesis inhibiting antibiotic administration. The interest of polyclonal intravenous immunoglobulin G administration as an adjunctive treatment for TSS requires further evaluation. Scientific literature on TSS mainly consists of observational studies, clinical cases, and in vitro data; although more data on TSS are required, additional studies will be difficult to conduct due to the low incidence of the disease.

Introduction Ventilator-associated pneumonia (VAP) remains the leading cause of infections treated in the intensive care units (ICU). In a personalised care approach, we hypothesise that the duration of treatment of VAP can be reduced in function of the response to treatment.Methods and analysis The Antimicrobial Stewardship for Ventilator-Associated Pneumonia in Intensive Care (ASPIC) trial is a pragmatic national multicentre, phase III, non-inferiority, comparative randomised (1:1) single-blinded clinical trial. Five hundred and ninety adult patients hospitalised in 24 French ICU with a microbiologically confirmed first episode of VAP that received appropriate empirical antibiotic therapy will be included. They will be randomly allocated to standard management with duration of appropriate antibiotic fixed for 7 days according to international guidelines or antimicrobial stewardship based on daily clinical assessment of clinical cure. The assessment of clinical cure will be repeated daily until at least three criteria of clinical cure are met, allowing the discontinuation of antibiotic therapy in experimental group. The primary endpoint is a composite endpoint combining of all-cause mortality measured at day 28, treatment failure or new episode of microbiologically confirmed VAP until day 28.The aim of the study is to demonstrate that a strategy to reduce the duration of antibiotic therapy for VAP based on clinical assessment is safe could lead to changes in practice as part of a personalised therapeutic approach, by reducing exposure to antibiotics and their side effects.Ethics and dissemination The ASPIC trial has been approved by the French regulatory agency (Agence Nationale de Sécurité du Médicament et des Produits de Santé, ANSM; EUDRACT number 2021-002197-78, 19 August 2021) and an independent ethics committee the Comité de Protection des Personnes Ile-de-France III (CNRIPH : 21.03.25.60729, 10 October 2021) for the study protocol (version ASPIC−1.3; 03 September 2021) for all study centres. Participant recruitment is scheduled to begin in 2022. Results will be published in international peer-reviewed medical journals.Trial registration number NCT05124977.

Abstract COVID-19 can cause acute respiratory distress syndrome, leading to death in many individuals. Evidence of a deleterious role of the innate immune system is accumulating, but the precise mechanisms involved remain unclear. In this study, we investigated the links between circulating innate phagocytes and severity in COVID-19 patients. We performed in-depth phenotyping of neutrophil and monocyte subpopulations and measured soluble activation markers in plasma. Additionally, anti-microbial functions (phagocytosis, oxidative burst, and NETosis) were evaluated on fresh cells from patients. Neutrophils and monocytes had a strikingly disturbed phenotype, and elevated concentrations of activation markers (calprotectin, myeloperoxidase, and neutrophil extracellular traps) were measured in plasma. Critical patients had increased CD13low immature neutrophils, LOX-1 + and CCR5 + immunosuppressive neutrophils, and HLA-DRlow downregulated monocytes. Markers of immature and immunosuppressive neutrophils were strongly associated with severity. Moreover, neutrophils and monocytes of critical patients had impaired antimicrobial functions, which correlated with organ dysfunction, severe infections, and mortality. Together, our results strongly argue in favor of a pivotal role of innate immunity in COVID-19 severe infections and pleads for targeted therapeutic options.

Abstract Immunocompromised patients are a heterogeneous and diffuse category frequently presenting to the emergency department with acute surgical diseases. Diagnosis and treatment in immunocompromised patients are often complex and must be multidisciplinary. Misdiagnosis of an acute surgical disease may be followed by increased morbidity and mortality. Delayed diagnosis and treatment of surgical disease occur; these patients may seek medical assistance late because their symptoms are often ambiguous. Also, they develop unique surgical problems that do not affect the general population. Management of this population must be multidisciplinary. This paper presents the World Society of Emergency Surgery (WSES), Surgical Infection Society Europe (SIS-E), World Surgical Infection Society (WSIS), American Association for the Surgery of Trauma (AAST), and Global Alliance for Infection in Surgery (GAIS) joined guidelines about the management of acute abdomen in immunocompromised patients.

Abstract Extracorporeal membrane oxygenation (ECMO), a relevant technology for patients with acute respiratory distress syndrome (ARDS) or acute cardiac failure (ACF), is a frequent cause of systemic inflammatory response syndrome. During sepsis, HDL cholesterol (HDL-C) and LDL cholesterol (LDL-C) concentrations decrease, and an association between low lipoprotein levels and poor outcomes was reported. There are no data from patients undergoing ECMO. The goal of this study was to characterize the lipoprotein profiles of ICU patients requiring ECMO. All consecutive patients admitted for ARDS or ACF requiring ECMO were prospectively included. Daily lipoprotein levels and short-term prognosis outcome were assessed. 25 patients were included. On admission, lipoprotein concentrations were low, under the reference values ([HDL-C] = 0.6[0.4–0.8]mmol/L;[LDL-C] = 1.3[1.0–1.7]mmol/L). A statistically significant rise in lipoproteins overtime was observed during the ICU stay. We found no relationship between lipoproteins concentrations and mortality on Day-28 (p = 0.689 and p = 0.979, respectively). Comparison of surviving patients with non-surviving patients did not reveal any differences in lipoproteins concentrations. Stratification between septic and non-septic patients demonstrated that septic patients had lower lipoproteins concentrations on admission (HDL-C: 0.5[0.3–0.6]mmol/l vs 0.8[0.6–0.9]mmol/l, p = 0.003; LDL-C: 1.1[0.9–1.5]mmol/l vs 1.5[1.3–2.6]mmol/l; p = 0.012), whereas these two groups were comparable in terms of severity and outcomes. HDL-C concentrations during ICU hospitalization were also significantly lower in the septic group than in the non-septic group (p = 0.035). In conclusion, Lipoprotein concentrations are low in patients requiring ECMO but are not associated with poor outcomes. The subpopulation of septic patients had lower lipoprotein levels overtime, which reinforces the potential key-role of these particles during sepsis.

Abstract The pathogenic role of staphylococci in hospital-acquired postoperative intra-abdominal infections (HAIs) has never been evaluated. In a tertiary care university hospital, we assessed the clinical characteristics and outcomes of patients admitted to the intensive care unit for HAIs according to the presence of staphylococci (S-HAI) or their absence (nS-HAI) in peritoneal cultures. Patients with S-HAIs were compared to nS-HAIs patients. Overall, 380 patients were analyzed, including 87 (23%) S-HAI patients [29 Staphylococcus aureus (Sa-HAIs) and 58 coagulase-negative staphylococci (CoNS-HAIs)]. The clinical characteristics did not differ between the S-HAI and nS-HAI patients. Adequacy of empirical anti-infective therapy was achieved less frequently in the staphylococci group (54 vs 72%, respectively, p

Abstract Background Anemia is a significant problem in patients on ICU. Its commonest cause, iron deficiency (ID), is difficult to diagnose in the context of inflammation. Hepcidin is a new marker of ID. We aimed to assess whether hepcidin levels would accurately guide treatment of ID in critically ill anemic patients after a prolonged ICU stay and affect the post-ICU outcomes. Methods In a controlled, single-blinded, multicenter study, anemic (WHO definition) critically ill patients with an ICU stay ≥ 5 days were randomized when discharge was expected to either intervention by hepcidin treatment protocol or control. In the intervention arm, patients were treated with intravenous iron (1 g of ferric carboxymaltose) when hepcidin was

Abstract Coronavirus disease 2019 (COVID-19) pandemic is affecting millions of patients worldwide. The consequences of initial exposure to SARS-CoV-2 go beyond pulmonary damage, with a particular impact on lipid metabolism. Decreased levels in HDL-C were reported in COVID-19 patients. Since HDL particles display antioxidant, anti-inflammatory and potential anti-infectious properties, we aimed at characterizing HDL proteome and functionality during COVID-19 relative to healthy subjects. HDLs were isolated from plasma of 8 severe COVID-19 patients sampled at admission to intensive care unit (Day 1, D1) at D3 and D7, and from 16 sex- and age-matched healthy subjects. Proteomic analysis was performed by LC-MS/MS. The relative amounts of proteins identified in HDLs were compared between COVID-19 and controls. apolipoprotein A-I and paraoxonase 1 were confirmed by Western-blot analysis to be less abundant in COVID-19 versus controls, whereas serum amyloid A and alpha-1 antitrypsin were higher. HDLs from patients were less protective in endothelial cells stiumalted by TNFα (permeability, VE-cadherin disorganization and apoptosis). In these conditions, HDL inhibition of apoptosis was blunted in COVID-19 relative to controls. In conclusion, we show major changes in HDL proteome and decreased functionality in severe COVID-19 patients.

Abstract Background High-density lipoproteins (HDLs), particles characterized by their reverse cholesterol transport function, display pleiotropic properties, including anti-inflammatory and antioxidant functions. Moreover, all lipoproteins (HDLs but also low-density lipoproteins (LDLs)) neutralize lipopolysaccharides, leading to increased bacterial clearance. These two lipoproteins decrease during sepsis, and an association between low lipoprotein levels and poor outcome was reported. The goals of this study were to characterize the lipid profile of septic patients hospitalized in our intensive care unit (ICU) and to determine the relationship with the outcome. Methods A prospective observational study was conducted in a university hospital ICU. All consecutive patients admitted for septic shock or sepsis were included. Total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglyceride levels were assessed at admission (day 1), at day 3, and at ICU discharge. When available, a prehospitalization lipid profile collected prior to the patient’s hospitalization was compiled. Short-term and 1-year prognostic outcomes were prospectively assessed. Results A total of 205 patients were included. We found a decrease in HDL-C concentration between previous values and those at admission, followed by an additional decrease at day 3. At ICU discharge, the concentration was higher than that at day 3 but did not reach the concentration measured prior to hospitalization (prior HDL-C = 1.22 (1.04–1.57) mmol/l; day 1 HDL-C = 0.44 (0.29–0.70) mmol/l; day 3 HDL-C = 0.30 (0.25–0.48) mmol/l; and HDL-C at discharge = 0.65 (0.42–0.82) mmol/l). A similar trend was found for LDL-C (prior LDL-C = 2.7 (1.91–3.33) mmol/l; day 1 LDL-C = 1.0 (0.58–1.50) mmol/l; day 3 LDL-C = 1.04 (0.64–1.54) mmol/l; and LDL-C at discharge = 1.69 (1.26–2.21) mmol/l). Mixed models for repeated measures of lipoprotein concentrations showed a significant difference in HDL-C and LDL-C concentrations over time between survivors and nonsurvivors at day 28. An HDL-C concentration at admission of less than 0.4 mmol/l was associated with increased mortality at day 28 (log-rank test, p = 0.034) but not at 1 year (log-rank test, p = 0.24). An LDL-C concentration at admission of less than 0.72 mmol/l was associated with increased mortality at day 28 and at 1 year (log-rank test, p

Abstract Background Aminoglycosides have a concentration-dependent therapeutic effect when peak serum concentration (C max) reaches eight to tenfold the minimal inhibitory concentration (MIC). With an amikacin MIC of 8 mg/L, the C max should be 64–80 mg/L. This objective is based on clinical breakpoints and not on measured MIC. This study aimed to assess the proportion of patients achieving the pharmacokinetic/pharmacodynamic (PK/PD) target C max/MIC ≥ 8 using the measured MIC in critically ill patients treated for documented Gram-negative bacilli (GNB) infections. Methods Retrospective analysis from February 2016 to December 2017 of a prospective database conducted in 2 intensive care units (ICU). All patients with documented severe GNB infections treated with amikacin (single daily dose of 25 mg/kg of total body weight (TBW)) with both MIC and C max measurements at first day of treatment (D1) were included. Results are expressed in n (%) or median [min–max]. Results 93 patients with 98 GNB-documented infections were included. The median C max was 55.2 mg/L [12.2–165.7] and the median MIC was 2 mg/L [0.19–16]. C max/MIC ratio ≥ 8 was achieved in 87 patients (88.8%) while a C max ≥ 64 mg/L was achieved in only 38 patients (38.7%). Overall probability of PK/PD target attainment was 93%. No correlation was found between C max/MIC ratio and clinical outcome at D8 and D28. Conclusion According to PK/PD parameters observed in our study, single daily dose of amikacin 25 mg/kg of TBW appears to be sufficient in most critically ill patients treated for severe GNB infections.

Abstract Background Early appropriate antibiotic therapy reduces morbidity and mortality of severe pneumonia. However, the emergence of bacterial resistance requires the earliest use of antibiotics with the narrowest possible spectrum. The Unyvero Hospitalized Pneumonia (HPN, Curetis) test is a multiplex PCR (M-PCR) system detecting 21 bacteria and 19 resistance genes on respiratory samples within 5 h. We assessed the performance and the potential impact of the M-PCR on the antibiotic therapy of ICU patients. Methods In this prospective study, we performed a M-PCR on bronchoalveolar lavage (BAL) or plugged telescoping catheter (PTC) samples of patients with ventilated HAP or VAP with Gram-negative bacilli or clustered Gram-positive cocci. This study was conducted in 3 ICUs in a French academic hospital: the medical and infectious diseases ICU, the surgical ICU, and the cardio-surgical ICU. A multidisciplinary expert panel simulated the antibiotic changes they would have made if the M-PCR results had been available. Results We analyzed 95 clinical samples of ventilated HAP or VAP (72 BAL and 23 PTC) from 85 patients (62 males, median age 64 years). The median turnaround time of the M-PCR was 4.6 h (IQR 4.4–5). A total of 90/112 bacteria were detected by the M-PCR system with a global sensitivity of 80% (95% CI, 73–88%) and specificity of 99% (95% CI 99–100). The sensitivity was better for Gram-negative bacteria (90%) than for Gram-positive cocci (62%) (p = 0.005). Moreover, 5/8 extended-spectrum beta-lactamases (CTX-M gene) and 4/4 carbapenemases genes (3 NDM, one oxa-48) were detected. The M-PCR could have led to the earlier initiation of an effective antibiotic in 20/95 patients (21%) and to early de-escalation in 37 patients (39%) but could also have led to one (1%) inadequate antimicrobial therapy. Among 17 empiric antibiotic treatments with carbapenems, 10 could have been de-escalated in the following hours according to the M-PCR results. The M-PCR also led to 2 unexpected diagnosis of severe legionellosis confirmed by culture methods. Conclusions Our results suggest that the use of a M-PCR system for respiratory samples of patients with VAP and ventilated HAP could improve empirical antimicrobial therapy and reduce the use of broad-spectrum antibiotics.

Abstract Background Some guidelines advocate for managing patients with penetrating thoracic wounds in trauma centres with cardiothoracic surgery. This systematic approach is questionable. Only 15% of these patients require surgery. It is known that clinical examination fails to detect hemopneumothorax in penetrating trauma. However, no studies have evaluated the combined diagnostic performance of vital signs and the clinical evaluation of wounds. The clinical characteristics of wounds have not been investigated. We aimed to evaluate the ability of combinations of pre-hospital signs to rule out invasive chest stab trauma. Methods This was a prospective observational study. All consecutive adult patients hospitalized in the perioperative acute care unit of a tertiary university hospital were included. Injury diagnoses were provided by exploratory surgery and imaging tests. Patients with a final diagnosis of invasive wounds (IWs) and patients with only superficial wounds were compared. Data regarding management and outcome were analysed. Results A total of 153 patients were included. After imaging or surgery, 58 (38%) patients were diagnosed with only superficial wounds, and 95 (62%) were diagnosed with thoracic or abdominal IWs. The false-negative rate of pre-hospital evaluations in the diagnosis of IWs was 42% [31–51]IQR25–75. In stable patients, pre-hospital data could not rule out IWs, with a negative predictive value of 58% and a positive predictive value of 70%. Twenty-nine (19%) patients required early emergent cardiothoracic surgery. Among these patients, 8 (28%) had no evidence of IWs in the pre-hospital period. Among the 59 patients without pre-hospital signs of IWs, 19 (33%) underwent at least one emergent procedure. Conclusions The combination of pre-hospital vital signs, visual evaluation of wounds, and physical examination failed to rule out IWs in patients with chest stab wounds. This implies that caution is needed in triage decision-making.

Abstract High-density lipoproteins (HDLs) represent a family of particle characterized by the presence of apolipoprotein A-I (apoA-I) and by their ability to transport cholesterol from peripheral tissues back to the liver conferring them a cardioprotective function. HDLs also display pleiotropic properties including antioxidant, anti-apoptotic, anti-thrombotic, anti-inflammatory, or anti-infectious functions. Clinical data demonstrate that HDL cholesterol levels decrease rapidly during sepsis and that these low levels are correlated with morbi-mortality. Experimental studies emphasized notable structural and functional modifications of HDL particles in inflammatory states, including sepsis. Finally, HDL infusion in animal models of sepsis improved survival and provided a global endothelial protective effect. These clinical and experimental studies reinforce the potential of HDL therapy in human sepsis. In this review, we will detail the different effects of HDLs that may be relevant under inflammatory conditions and the lipoprotein changes during sepsis and we will discuss the potentiality of HDL therapy in sepsis.

Background High-density lipoproteins (HDLs) are synthesized by the liver and display endothelioprotective properties, including anti-inflammatory, antiapoptotic, antithrombotic and antioxidant effects. In both septic and chronic liver failure patients, a low HDL cholesterol (HDL-C) concentration is associated with overmortality. Whereas sepsis-associated liver dysfunction is poorly defined, the aim of this study was to characterize the relationship between liver dysfunction, lipoprotein concentrations and mortality in septic patients in the intensive care unit (ICU). Methods A prospective observational study was conducted in a university hospital ICU. All consecutive patients admitted for septic shock or sepsis were included. Total cholesterol, HDL-C, low-density lipoprotein-cholesterol (LDL-C), and triglyceride levels were assessed at admission. Sepsis-associated liver dysfunction was defined as a serum bilirubin≥ 2N or aspartate aminotransferase/alanine aminotransferase concentrations ≥ 2N. Short-term and one-year prognostic outcomes were prospectively assessed. Results A total of 219 septic patients were included, and 15% of them presented with sepsis-associated liver dysfunction at admission. Low concentrations of lipoproteins were associated with mortality at Day 28 in the overall population. Sepsis-associated liver dysfunction at admission was associated with overmortality. In this subgroup, patients had a lower HDL-C concentration than patients without hepatic dysfunction (HDL-C = 0.31 [0.25, 0.55] mmol/L vs. 0.48 [0.29, 0.73] mmol/L, p = 0.0079) but there was no relationship with the outcome. Interestingly, no correlation was observed between lipoprotein concentrations and liver dysfunction markers. Conclusion Sepsis-associated liver dysfunction at ICU admission is strongly associated with overmortality and is associated with a lower HDL-C concentration. However, in this subgroup of patients, HDL-C concentration had no relationship with mortality. Further exploratory studies are needed to better understand the interaction between lipoproteins and liver dysfunction during sepsis.

Introduction More than 300 million surgical procedures are performed each year. Acute kidney injury (AKI) is a common complication after major surgery and is associated with adverse short-term and long-term outcomes. However, there is a large variation in the incidence of reported AKI rates. The establishment of an accurate epidemiology of surgery-associated AKI is important for healthcare policy, quality initiatives, clinical trials, as well as for improving guidelines. The objective of the Epidemiology of Surgery-associated Acute Kidney Injury (EPIS-AKI) trial is to prospectively evaluate the epidemiology of AKI after major surgery using the latest Kidney Disease: Improving Global Outcomes (KDIGO) consensus definition of AKI.Methods and analysis EPIS-AKI is an international prospective, observational, multicentre cohort study including 10 000 patients undergoing major surgery who are subsequently admitted to the ICU or a similar high dependency unit. The primary endpoint is the incidence of AKI within 72 hours after surgery according to the KDIGO criteria. Secondary endpoints include use of renal replacement therapy (RRT), mortality during ICU and hospital stay, length of ICU and hospital stay and major adverse kidney events (combined endpoint consisting of persistent renal dysfunction, RRT and mortality) at day 90. Further, we will evaluate preoperative and intraoperative risk factors affecting the incidence of postoperative AKI. In an add-on analysis, we will assess urinary biomarkers for early detection of AKI.Ethics and dissemination EPIS-AKI has been approved by the leading Ethics Committee of the Medical Council North Rhine-Westphalia, of the Westphalian Wilhelms-University Münster and the corresponding Ethics Committee at each participating site. Results will be disseminated widely and published in peer-reviewed journals, presented at conferences and used to design further AKI-related trials.Trial registration number NCT04165369.

(1) Background: Cephalosporins (CA) are the first-line antibiotic prophylaxis recommended to prevent surgical site infection (SSI) after cardiac surgery. The combination of vancomycin/gentamicin (VGA) might represent a good alternative, but few studies have evaluated its efficacy in SSI prevention. (2) Methods: A single-centre retrospective study was conducted over a 13-year period in all consecutive adult patients undergoing elective cardiac surgery. Patients were stratified according to the type of antibiotic prophylaxis. CA served as the first-line prophylaxis, and VGA was used as the second-line prophylaxis. The primary endpoint was SSI occurrence at 90 days, which was defined as the need for reoperation due to SSI. (3) Results: In total, 14,960 adult patients treated consecutively from 2006 to 2019 were included in this study, of whom 1774 (12%) received VGA and 540 (3.7%) developed SSI. VGA patients had higher severity with increased 90-day mortality. Nevertheless, the frequency of SSI was similar between CA and VGA patients. However, the microbiological aetiologies were different, with more Gram-negative bacteria noted in the VGA group. (4) Conclusions: VGA seems to be as effective as CA in preventing SSI.

Abstract Background Recent international guidelines for acute pancreatitis (AP) recommend limiting anti-infective therapy (AIT) to cases of suspected necrotizing AP or nosocomial extrapancreatic infection. Limited data are available concerning empirical and documented AIT prescribing practices in patients admitted to the intensive care unit (ICU) for the management of AP. Methods Using a multicentre, retrospective (2009–2014), observational database of ICU patients admitted for AP, our primary objective was to assess the incidence of AIT prescribing practices during the first 30 days following admission. Secondary objectives were to assess the independent impact of centre characteristics on the incidence of AIT and to identify factors associated with crude hospital mortality in a logistic regression model. Results In this cohort of 860 patients, 359 (42%) received AIT on admission. Before day 30, 340/359 (95%) AIT patients and 226/501 (45%) AIT-free patients on admission received additional AIT, mainly for intra-abdominal and lung infections. A large heterogeneity was observed between centres in terms of the incidence of infections, therapeutic management including AIT and prognosis. Administration of AIT on admission or until day 30 was not associated with an increased mortality rate. Patients receiving AIT on admission had increased rates of complications (septic shock, intra-abdominal and pulmonary infections), therapeutic (surgical, percutaneous, endoscopic) interventions and increased length of ICU stay compared to AIT-free patients. Patients receiving delayed AIT after admission and until day 30 had increased rates of complications (respiratory distress syndrome, intra-abdominal and pulmonary infections), therapeutic interventions and increased length of ICU stay compared to those receiving AIT on admission. Risk factors for hospital mortality assessed on admission were age (adjusted odds ratio [95% confidence interval] 1.03 [1.02–1.05]; p

Abstract Background The objective of this study was to assess the cumulative incidence of invasive candidiasis (IC) in intensive care units (ICUs) in Europe. Methods A multinational, multicenter, retrospective study was conducted in 23 ICUs in 9 European countries, representing the first phase of the candidemia/intra-abdominal candidiasis in European ICU project (EUCANDICU). Results During the study period, 570 episodes of ICU-acquired IC were observed, with a cumulative incidence of 7.07 episodes per 1000 ICU admissions, with important between-center variability. Separated, non-mutually exclusive cumulative incidences of candidemia and IAC were 5.52 and 1.84 episodes per 1000 ICU admissions, respectively. Crude 30-day mortality was 42%. Age (odds ratio [OR] 1.04 per year, 95% CI 1.02–1.06, p

Abstract Background Sepsis is associated with systemic inflammation that may impact lipoprotein function. In particular, high-density lipoproteins (HDLs) that display pleiotropic protective roles may be dysfunctional in septic conditions. The aim of this study was to evaluate the HDL profile and the inflammatory context in septic shock patients admitted to our intensive care unit (ICU). Methods In this study, 20 septic shock patients and 20 controls (ICU patients without septic shock) were included. Plasma samples were collected on days 1, 2 and 7. Total cholesterol and lipoprotein concentrations were determined. HDL profiles were obtained using the Lipoprint® System (non-denaturing electrophoresis). Quantification of pro-inflammatory cytokines (interleukin 1b, 6 and 8), cell-free DNA and lipopolysaccharide-binding protein was also performed. Results HDL concentration was statistically lower in septic shock patients than in controls. At days 1 and 2, septic patients had significantly more large-sized HDL than control patients. Patients recovered a normal lipid profile at day 7. Conclusions Our results emphasize that HDL levels are dramatically decreased in the acute phase of septic shock and that there is a shift toward large HDL particles, which may reflect a major dysfunction of these lipoproteins. Further mechanistic studies are required to explore this shift observed during sepsis.

We aimed to describe the prevalence, risk factors, morbidity and mortality associated with the occurrence of bacteraemia during the postoperative ICU stay after lung transplantation (LT). We conducted a retrospective single-centre study that included all consecutive patients who underwent LT between January 2015 and October 2021. We analysed all the blood cultures drawn during the postoperative ICU stay, as well as samples from suspected infectious sources in case of bacteraemia. Forty-six bacteria were isolated from 45 bacteraemic patients in 33/303 (10.9%) patients during the postoperative ICU stay. Staphylococcus aureus (17.8%) was the most frequent bacteria, followed by Pseudomonas aeruginosa (15.6%) and Enterococcus faecium (15.6%). Multidrug-resistant bacteria accounted for 8/46 (17.8%) of the isolates. The most common source of bacteraemia was pneumonia (38.3%). No pre- or intraoperative risk factor for bacteraemia was identified. Recipients who experienced bacteraemia required more renal replacement therapy, invasive mechanical ventilation, norepinephrine support, tracheotomy and more days of hospitalization during the ICU stay. After adjustment for age, sex, type of LT procedure and the need for intraoperative ECMO, the occurrence of bacteraemia was associated with a higher mortality rate in the ICU (aOR = 3.55, 95% CI [1.56–8.08], p = 0.003). Bacteraemia is a major source of concern for lung transplant recipients.

Introduction: Recent studies described the threat of emerging multidrug-resistant (MDR) bacteria in intensive care unit (ICU) patients, but few data are available for necrotizing skin and soft tissue infections (NSTI). In a cohort of ICU patients admitted for NSTI, we describe the dynamic changes of microbial population during repeated surgeries.Materials and Methods: This retrospective study compiled consecutive cases admitted for the management of severe NSTI. Clinical characteristics, NSTI features, morbidity and mortality data were collected. The microbiological characteristics of surgical samples obtained during initial surgery were compared with those obtained during the first reoperation, including persistence of initial pathogens and/or emergence of microorganisms. Risk factors for emergence of microorganisms and MDR bacteria were assessed by univariable and multivariable analyses.Results: Among 100 patients {63% male, 58 years old [interquartile ratio (IQR) 50–68]} admitted for NSTI, 54 underwent reoperation with a median [IQR] delay of 3 (1–7) days. Decreased proportions of susceptible strains and emergence of Gram-negative bacteria, including Pseudomonas aeruginosa, staphylococci and enterococci strains, were reported based on the cultures of surgical specimen collected on reoperation. On reoperation, 22 (27%) of the isolated strains were MDR (p < 0.0001 vs. MDR bacteria cultured from the first samples). Broad-spectrum antibiotic therapy as first-line therapy was significantly associated with a decreased emergence of microorganisms. Adequate antibiotic therapy from the initial surgery did not modify the frequency of emergence of microorganisms (p = 0.79) and MDR bacteria (p = 1.0) or the 1-year survival rate.Conclusion: The emergence of microorganisms, including MDR bacteria, is frequently noted in NSTI without affecting mortality.

Among 197 COVID-19 patients hospitalized in ICU, 88 (44.7%) experienced at least one bacterial infection, with pneumonia (39.1%) and bloodstream infections (15,7%) being the most frequent. Unusual findings include frequent suspicion of bacterial translocations originating from the digestive tract as well as bacterial persistence in the lungs despite adequate therapy.

BackgroundTracheostomy has been proposed as an option to help organize the healthcare system to face the unprecedented number of patients hospitalized for a COVID-19-related acute respiratory distress syndrome (ARDS) in intensive care units (ICU). It is, however, considered a particularly high-risk procedure for contamination. This paper aims to provide our experience in performing tracheostomies on COVID-19 critically ill patients during the pandemic and its long-term local complications.MethodsWe performed a retrospective analysis of prospectively collected data of patients tracheostomized for a COVID-19-related ARDS in two university hospitals in the Paris region between January 27th (date of first COVID-19 admission) and May 18th, 2020 (date of last tracheostomy performed). We focused on tracheostomy technique (percutaneous versus surgical), timing (early versus late) and late complications.ResultsForty-eight tracheostomies were performed with an equal division between surgical and percutaneous techniques. There was no difference in patients' characteristics between surgical and percutaneous groups. Tracheostomy was performed after a median of 17 [12-22] days of mechanical ventilation (MV), with 10 patients in the "early" group (≤ day 10) and 38 patients in the "late" group (> day 10). Survivors required MV for a median of 32 [22-41] days and were ultimately decannulated with a median of 21 [15-34] days spent on cannula. Patients in the early group had shorter ICU and hospital stays (respectively 15 [12-19] versus 35 [25-47] days; p = 0.002, and 21 [16-28] versus 54 [35-72] days; p = 0.002) and spent less time on MV (respectively 17 [14-20] and 35 [27-43] days; pConclusionsTracheostomy seems to be a safe procedure that could help ICU organization by delegating work to a separate team and favoring patient turnover by allowing faster transfer to step-down units. Following guidelines alone was found sufficient to prevent the risk of aerosolization and contamination of healthcare professionals.

[This corrects the article DOI: 10.1371/journal.pone.0243261.].

High-density lipoproteins (HDLs) have multiple endothelioprotective properties. During SARS-CoV-2 infection, HDL-cholesterol (HDL-C) concentration is markedly reduced, and studies have described severe impairment of the functionality of HDL particles. Here, we report a multi-omic investigation of the first administration of recombinant HDL (rHDL) particles in a severe COVID-19 patient in an intensive care unit. Plasma ApoA1 increased and HDL-C decreased after each recombinant HDL injection, suggesting that these particles were functional in terms of reverse cholesterol transport. The proportion of large HDL particles also increased after injection of recombinant HDL. Shotgun proteomics performed on HDLs isolated by ultracentrifugation indicated that ApoA1 was more abundant after injections whereas most of the pro-inflammatory proteins identified were less abundant. Assessment of Serum amyloid A-1, inflammatory markers, and cytokines showed a significant decrease for most of them during recombinant HDL infusion. Our results suggest that recombinant HDL infusion is feasible and a potential therapeutic strategy to be explored in COVID-19 patients.

Abstract Skin and soft-tissue infections (SSTIs) encompass a variety of pathological conditions that involve the skin and underlying subcutaneous tissue, fascia, or muscle, ranging from simple superficial infections to severe necrotizing infections. SSTIs are a frequent clinical problem in surgical departments. In order to clarify key issues in the management of SSTIs, a task force of experts met in Bertinoro, Italy, on June 28, 2018, for a specialist multidisciplinary consensus conference under the auspices of the World Society of Emergency Surgery (WSES) and the Surgical Infection Society Europe (SIS-E). The multifaceted nature of these infections has led to a collaboration among general and emergency surgeons, intensivists, and infectious disease specialists, who have shared these clinical practice recommendations.

Abstract 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.

Abstract Background CD31 is a key transmembrane neutrophil immunoregulatory receptor. Mesenteric ischemia/reperfusion-induced neutrophil activation leads to a massive cleavage and shedding of the most extracellular domains of CD31 into plasma, enhancing the deleterious effect of neutrophil activation. We have evaluated the preventive therapeutic potential of an engineered synthetic octapeptide (P8RI), which restores the inhibitory intracellular signaling of cleaved CD31, in an experimental model of acute mesenteric ischemia/reperfusion. Methods In a randomized, controlled, and experimenter-blinded preclinical study, mesenteric ischemia/reperfusion (I/R) was induced in Wistar rats by superior mesenteric artery occlusion for 30 min followed by 4 h of reperfusion. Three groups of rats were compared: I/R + saline perfusion (I/R controls group, n = 7), I/R + preventive P8RI perfusion (P8RI group, n = 7), and sham-operated rats + saline perfusion (sham group, n = 7). Results Compared with I/R controls, P8RI perfusion significantly decreased intestinal ischemia/reperfusion injury (Chiu’s score, P = 0.01; epithelial area, P = 0.001) and bacterial translocation (plasma Escherichia coli DNA, P = 0.04) and could limit intestinal bleeding (P = 0.09). P8RI decreased neutrophil activation assessed by matrix metalloproteinase-9 release in plasma (P

Abstract Background To compare the risk of severe hepatotoxicity with anidulafungin versus caspofungin and micafungin in hospitalized adults. Methods This retrospective cohort study combined data from two large US- based hospital electronic medical record databases. Severe hepatotoxicity was a Grade ≥ 3 liver function test (LFT) post-echinocandin initiation. Adjusted incidence rate ratios (IRRs) were estimated for anidulafungin versus caspofungin and micafungin, overall and in patients with normal baseline LFT (Grade 0). Results Treatments included anidulafungin (n = 1700), caspofungin (n = 4431), or micafungin (n = 6547). The proportions with LFT Grade ≥ 3 pre-echinocandin initiation were: anidulafungin 40.4% versus caspofungin 25.9% (p

Abstract Background Bloodstream infections of abdominal origin are usually associated with poor prognosis. We assessed the clinical and microbiological characteristics of critically ill patients admitted to the intensive care unit (ICU) for postoperative intra-abdominal infection (PIAI) and analysed the influence of bacteraemia on their outcome. Methods All consecutive PIAI patients admitted to the ICU between 1999 and 2014 were prospectively analysed. Bacteraemic patients (at least one positive blood culture in the 24 h preceding/following surgery) were compared with non-bacteraemic patients. Demographic characteristics, underlying disease, severity scores at the time of reoperation, microbiological results, therapeutic management, outcome, and survival were recorded. Results are expressed as median (interquartile range (IQR)) or proportions. Results Overall, 343 patients (54% male, 62 (49–73) years old) with PIAI were analysed, including 64 (19%) bacteraemic patients. Immunosuppression and cancer were more frequent in bacteraemic patients (p

Abstract Background Bacterial respiratory infections (BRI) are major complications contributing to increased morbidity and mortality after lung transplantation (LT). This study analyzed epidemiology and outcome of 175 consecutive patients developing BRI in ICU after LT between 2006 and 2012. Methods Three situations were described: colonization determined in donors and recipients, pneumonia and tracheobronchitis during the first 28 postoperative days. Severity score, demographic, bacteriologic and outcome data were collected. Results 26% of donors and 31% of recipients were colonized. 92% of recipients developed BRI, including at least one episode of pneumonia in 19% of recipients. Only 21% of recipients developed BRI with an organism cultured from the donor’s samples, while 40% of recipients developed BRI with their own bacteria cultured before LT. Purulent sputum appears to be an important factor to discriminate tracheobronchitis from pneumonia. When compared to patients with tracheobronchitis, those with pneumonia had longer durations of mechanical ventilation (13 [3–27] vs 3 [29], p = 0.0005) and ICU stay (24 [16–34] vs 14 [9-22], p = 0.002). Pneumonia was associated with higher 28-day (11 (32%) vs 9 (7%), p = 0.0004) and one-year mortality rates (21 (61%) vs 24 (19%), p ≤ 0.0001). Conclusions These data confirm the high frequency of BRI right from the early postoperative period and the poor prognosis of pneumonia after LT.

Abstract Damage control resuscitation may lead to postoperative intra-abdominal hypertension or abdominal compartment syndrome. These conditions may result in a vicious, self-perpetuating cycle leading to severe physiologic derangements and multiorgan failure unless interrupted by abdominal (surgical or other) decompression. Further, in some clinical situations, the abdomen cannot be closed due to the visceral edema, the inability to control the compelling source of infection or the necessity to re-explore (as a “planned second-look” laparotomy) or complete previously initiated damage control procedures or in cases of abdominal wall disruption. The open abdomen in trauma and non-trauma patients has been proposed to be effective in preventing or treating deranged physiology in patients with severe injuries or critical illness when no other perceived options exist. Its use, however, remains controversial as it is resource consuming and represents a non-anatomic situation with the potential for severe adverse effects. Its use, therefore, should only be considered in patients who would most benefit from it. Abdominal fascia-to-fascia closure should be done as soon as the patient can physiologically tolerate it. All precautions to minimize complications should be implemented.