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Background: Data are scarce regarding epidemiology and management of critically ill patients with lung abscesses., Research Question: What are the clinical and microbiological characteristics of critically ill patients with lung abscesses, how are they managed in the ICU, and what are the risk factors of in-ICU mortality?, Study Design and Methods: This was a retrospective observational multicenter study, based on International Classification of Diseases, 10th Revision, codes, between 2015 and 2022 in France. In-ICU mortality-associated factors were determined by multivariate logistic regression., Results: We analyzed 171 ICU patients with pulmonary abscesses. Seventy-eight percent were male, with a mean age of 56.5 ± 16.4 years; 20.4% misused alcohol, 25.2% had a chronic lung disease (14% COPD), and 20.5% had a history of cancer. Overall, 40.9% were immunocompromised and 38% qualified for nosocomial infection. Presenting symptoms included fatigue or weight loss in 62%, fever (50.3%), and dyspnea (47.4%). Hemoptysis was reported in 21.7%. A polymicrobial infection was present in 35.6%. The most frequent pathogens were Enterobacteriaceae in 31%, Staphylococcus aureus in 22%, and Pseudomonas aeruginosa in 19.3%. Fungal infections were found in 10.5%. Several clusters of clinicoradiologic patterns were associated with specific microbiological documentation and could guide empiric antibiotic regimen. Percutaneous abscess drainage was performed in 11.7%; surgery was performed in 12.7%, and 12% required bronchial artery embolization for hemoptysis. In-ICU mortality was 21.5%, and age (OR: 1.05 [1.02-1.91], P = .007], renal replacement therapy during ICU stay (OR, 3.56 [1.24-10.57], P = .019), and fungal infection (OR, 9.12 [2.69-34.5], P = .0006) were independent predictors of mortality after multivariate logistic regression, and drainage or surgery were not., Interpretation: Pulmonary abscesses in the ICU are a rare but severe disease often resulting from a polymicrobial infection, with a high proportion of Enterobacteriaceae, S aureus, and P aeruginosa. Percutaneous drainage, surgery, or arterial embolization was required in more than one-third of cases. Further prospective studies focusing on first-line antimicrobial therapy and source control procedure are warranted to improve and standardize patient management., Competing Interests: Financial/Nonfinancial Disclosures None declared., (Copyright © 2023 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Objectives: Respiratory syncytial virus (RSV) is a common agent of viral respiratory infections with significant morbidity and mortality in adults. The objective of this study was to determine risk factors for mortality and invasive mechanical ventilation and to describe the characteristics of patients who received ribavirin., Methods: A retrospective multicentre observational cohort study was conducted in Great Paris area hospitals, including patients hospitalised between 1 January 2015 and 31 December 2019 for documented RSV infection. Data were extracted from the Assistance Publique-Hôpitaux de Paris Health Data Warehouse. The primary endpoint was in-hospital mortality., Results: One thousand one hundred sixty-eight patients were hospitalised for RSV infection, including 288 (24.6%) patients who required intensive care unit (ICU) admission. The median (interquartile range) age of patients was 75 (63-85) years, and 54% (n = 631/1168) of them were women. In-hospital mortality was 6.6% (n = 77/1168) in the whole cohort and 12.8% (n = 37/288) in ICU patients. Factors associated with hospital mortality were age >85 years (adjusted odds ratio [aOR] = 6.29, 95% confidence interval [2.47-15.98]), acute respiratory failure (aOR = 2.83 [1.19-6.72]), non-invasive (aOR = 12.60 [1.41-112.36]), and invasive mechanical ventilation support (aOR = 30.13 [3.17-286.27]) and neutropenia (aOR = 13.19 [3.27-53.27]). Factors associated with invasive mechanical ventilation were chronic heart (aOR = 1.98 [1.20-3.26]) or respiratory failure (aOR = 2.83 [1.67-4.80]), and co-infection (aOR = 2.62 [1.60-4.30]). Patients who were treated with ribavirin were significantly younger than others (62 [55-69] vs. 75 [63-86] years; p < 0.001), more frequently males (n = 34/48 [70.8%] vs. n = 503/1120 [44.9%]; p 0.001), and almost exclusively immunocompromised (n = 46/48 [95.8%] vs. n = 299/1120 [26.7%]; p < 0.001)., Discussion: The mortality rate of patients hospitalised with RSV infections was 6.6%. Twenty-five per cent of the patients required ICU admission., (Copyright © 2023 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Background: Patients with severe COVID-19 have emerged as a population at high risk of invasive fungal infections (IFIs). However, to our knowledge, the prevalence of IFIs has not yet been assessed in large populations of mechanically ventilated patients. We aimed to identify the prevalence, risk factors, and mortality associated with IFIs in mechanically ventilated patients with COVID-19 under intensive care., Methods: We performed a national, multicentre, observational cohort study in 18 French intensive care units (ICUs). We retrospectively and prospectively enrolled adult patients (aged ≥18 years) with RT-PCR-confirmed SARS-CoV-2 infection and requiring mechanical ventilation for acute respiratory distress syndrome, with all demographic and clinical and biological follow-up data anonymised and collected from electronic case report forms. Patients were systematically screened for respiratory fungal microorganisms once or twice a week during the period of mechanical ventilation up to ICU discharge. The primary outcome was the prevalence of IFIs in all eligible participants with a minimum of three microbiological samples screened during ICU admission, with proven or probable (pr/pb) COVID-19-associated pulmonary aspergillosis (CAPA) classified according to the recent ECMM/ISHAM definitions. Secondary outcomes were risk factors of pr/pb CAPA, ICU mortality between the pr/pb CAPA and non-pr/pb CAPA groups, and associations of pr/pb CAPA and related variables with ICU mortality, identified by regression models. The MYCOVID study is registered with ClinicalTrials.gov, NCT04368221., Findings: Between Feb 29 and July 9, 2020, we enrolled 565 mechanically ventilated patients with COVID-19. 509 patients with at least three screening samples were analysed (mean age 59·4 years [SD 12·5], 400 [79%] men). 128 (25%) patients had 138 episodes of pr/pb or possible IFIs. 76 (15%) patients fulfilled the criteria for pr/pb CAPA. According to multivariate analysis, age older than 62 years (odds ratio [OR] 2·34 [95% CI 1·39-3·92], p=0·0013), treatment with dexamethasone and anti-IL-6 (OR 2·71 [1·12-6·56], p=0·027), and long duration of mechanical ventilation (>14 days; OR 2·16 [1·14-4·09], p=0·019) were independently associated with pr/pb CAPA. 38 (7%) patients had one or more other pr/pb IFIs: 32 (6%) had candidaemia, six (1%) had invasive mucormycosis, and one (<1%) had invasive fusariosis. Multivariate analysis of associations with death, adjusted for candidaemia, for the 509 patients identified three significant factors: age older than 62 years (hazard ratio [HR] 1·71 [95% CI 1·26-2·32], p=0·0005), solid organ transplantation (HR 2·46 [1·53-3·95], p=0·0002), and pr/pb CAPA (HR 1·45 [95% CI 1·03-2·03], p=0·033). At time of ICU discharge, survival curves showed that overall ICU mortality was significantly higher in patients with pr/pb CAPA than in those without, at 61·8% (95% CI 50·0-72·8) versus 32·1% (27·7-36·7; p<0·0001)., Interpretation: This study shows the high prevalence of invasive pulmonary aspergillosis and candidaemia and high mortality associated with pr/pb CAPA in mechanically ventilated patients with COVID-19. These findings highlight the need for active surveillance of fungal pathogens in patients with severe COVID-19., Funding: Pfizer., Competing Interests: Declaration of interests J-PG reports personal fees from Gilead and grants and personal fees from Pfizer, outside of the submitted work. ED reports grants and non-financial support from Merck Sharp & Dohme and Gilead and non-financial support from Pfizer and Astellas, outside of the submitted work. AF reports personal fees and non-financial support from Merck Sharp & Dohme, grants from Janssen, personal fees and non-financial support from Gilead, and non-financial support from Pfizer, outside of the submitted work. C-EL reports personal fees from Carmat, Merck, BioMérieux, Brahms (part of Thermo Fisher Scientific), Bayer Healthcare, and Faron, outside of the submitted work. FraB reports grants from Astellas, personal fees from Merck Sharp & Dohme, and non-financial support from Pfizer, Merck Sharp & Dohme, and Astellas, outside of the submitted work. J-FT reports personal fees from Pfizer, Merck, Astellas, and Gilead, outside of the submitted work. FP reports non-financial support from Gilead and Pfizer, outside of the submitted work. EmC reports personal fees from Gilead, Baxter, and Sanofi-Genzyme, outside of the submitted work. AA reports personal fees from Pfizer and Gilead, outside of the submitted work. MC reports grants from Pfizer, outside of the submitted work. JuM reports non-financial support from Gilead, outside of the submitted work. SE reports grants, personal fees, and non-financial support from Aerogen and Fisher & Paykel, outside of the submitted work. GV reports grants and personal fees from BioMérieux and grants from SOS Oxygène and Janssen, outside of the submitted work. JeM reports grants from Pfizer and Gilead, outside of the submitted work. J-RZ reports grants and personal fees from Merck Sharp & Dohme and personal fees from Novartis and Pfizer, outside of the submitted work. M-EB reports grants from Pfizer during the conduct of the study; grants and non-financial support from Gilead and Pfizer, and non-financial support from Merck Sharp & Dohme, outside of the submitted work. All other authors declare no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Introduction: In France, at the end of the sixth year of medical studies, students take a national ranking examination including progressive clinical case-based multiple-choice questions (MCQs). We aimed to evaluate the ability of these MCQs for testing higher-order thinking more than knowledge recall, and to identify their characteristics associated with success and discrimination., Methods: We analysed the 72 progressive clinical cases taken by the students in the years 2016-2019, through an online platform., Results: A total of 72 progressive clinical cases (18 for each of the 4 studied years), corresponding to 1059 questions, were analysed. Most of the clinical cases (n=43, 60%) had 15 questions. Clinical questions represented 89% of all questions, whereas basic sciences questions accounted for 9%. The most frequent medical subspecialties were internal medicine (n=90, 8%) and infectious diseases (n=88, 8%). The most frequent question types concerned therapeutics (26%), exams (19%), diagnosis (14%), and semiology (13%). Level 2 questions ("understand and apply") accounted for 59% of all questions according to the Bloom's taxonomy. The level of Bloom's taxonomy significantly changed over time with a decreasing number of level 1 questions ("remember") (P=0.04). We also analysed the results of the students among 853 questions of training ECNi. Success and discrimination significantly decreased when the number of correct answers increased (P<0.0001 both). The success, discrimination, mean score, and mean number of discrepancies did not differ according to the diagnosis, exam, imaging, semiology, or therapeutic type of questions., Conclusion: Progressive clinical case-based MCQs represent an innovative way to evaluate undergraduate students., (Copyright © 2020 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier Masson SAS. All rights reserved.)

Background: Delaying renal replacement therapy (RRT) for some time in critically ill patients with severe acute kidney injury and no severe complication is safe and allows optimisation of the use of medical devices. Major uncertainty remains concerning the duration for which RRT can be postponed without risk. Our aim was to test the hypothesis that a more-delayed initiation strategy would result in more RRT-free days, compared with a delayed strategy., Methods: This was an unmasked, multicentre, prospective, open-label, randomised, controlled trial done in 39 intensive care units in France. We monitored critically ill patients with severe acute kidney injury (defined as Kidney Disease: Improving Global Outcomes stage 3) until they had oliguria for more than 72 h or a blood urea nitrogen concentration higher than 112 mg/dL. Patients were then randomly assigned (1:1) to either a strategy (delayed strategy) in which RRT was started just after randomisation or to a more-delayed strategy. With the more-delayed strategy, RRT initiation was postponed until mandatory indication (noticeable hyperkalaemia or metabolic acidosis or pulmonary oedema) or until blood urea nitrogen concentration reached 140 mg/dL. The primary outcome was the number of days alive and free of RRT between randomisation and day 28 and was done in the intention-to-treat population. The study is registered with ClinicalTrial.gov, NCT03396757 and is completed., Findings: Between May 7, 2018, and Oct 11, 2019, of 5336 patients assessed, 278 patients underwent randomisation; 137 were assigned to the delayed strategy and 141 to the more-delayed strategy. The number of complications potentially related to acute kidney injury or to RRT were similar between groups. The median number of RRT-free days was 12 days (IQR 0-25) in the delayed strategy and 10 days (IQR 0-24) in the more-delayed strategy (p=0·93). In a multivariable analysis, the hazard ratio for death at 60 days was 1·65 (95% CI 1·09-2·50, p=0·018) with the more-delayed versus the delayed strategy. The number of complications potentially related to acute kidney injury or renal replacement therapy did not differ between groups., Interpretation: In severe acute kidney injury patients with oliguria for more than 72 h or blood urea nitrogen concentration higher than 112 mg/dL and no severe complication that would mandate immediate RRT, longer postponing of RRT initiation did not confer additional benefit and was associated with potential harm., Funding: Programme Hospitalier de Recherche Clinique., Competing Interests: Declaration of interests The authors declare no competing interests. The AKIKI 2 trial was promoted by the Assistance Publique—Hôpitaux de Paris and funded by a grant of the French Ministry of Health (Programme Hospitalier de Recherche Clinique 2016; AOM16278)., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: The antiphospholipid syndrome (APS) is a systemic autoimmune disease defined by thrombotic events that can require ICU admission because of organ dysfunction related to macrovascular and/or microvascular thrombosis. Critically ill patients with thrombosis and APS were studied to gain insight into their prognoses and in-hospital mortality-associated factors., Methods: This French national, multicenter, retrospective study included all patients with APS and any new thrombotic manifestations admitted to 24 ICUs (January 2000-September 2018)., Results: During the study period, 134 patients (male/female ratio, 0.4) with 152 APS episodes were admitted to the ICU (mean age at admission, 46.0 ± 15.1 years). In-hospital mortality of their 134 last episodes was 35 of 134 (26.1%). The Cox multivariable model retained certain factors (hazard ratio [95% CI]: age ≥ 40 years, 11.4 [3.1-41.5], P < .0001; mechanical ventilation, 11.0 [3.3-37], P < .0001; renal replacement therapy, 2.9 [1.3-6.3], P = .007; and in-ICU anticoagulation, 0.1 [0.03-0.3], P < .0001) as independently associated with in-hospital mortality. For the subgroup of definite/probable catastrophic APS, the Cox bivariable model (including the Simplified Acute Physiology Score II score) retained double therapy (corticosteroids + anticoagulant, 0.2 [0.07-0.6]; P = .005) but not triple therapy (corticosteroids + anticoagulant + IV immunoglobulins or plasmapheresis: hazard ratio, 0.3 [0.1-1.1]; P = .07) as independently associated with in-hospital mortality., Conclusions: In-ICU anticoagulation was the only APS-specific treatment independently associated with survival for all patients. Double therapy was independently associated with better survival of patients with definite/probable catastrophic APS. In these patients, further studies are needed to determine the role of triple therapy., (Copyright © 2019 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Background: Necrotizing skin and soft-tissue infections (NSTI) are rare but potentially life-threatening and disabling infections that often require intensive care unit admission., Objectives: To review all aspects of care for a critically ill individual with NSTI., Sources: Literature search using Medline and Cochrane library, multidisciplinary panel of experts., Content: The initial presentation of a patient with NSTI can be misleading, as features of severe systemic toxicity can obscure sometimes less impressive skin findings. The infection can spread rapidly, and delayed surgery worsens prognosis, hence there is a limited role for additional imaging in the critically ill patient. Also, the utility of clinical scores is contested. Prompt surgery with aggressive debridement of necrotic tissue is required for source control and allows for microbiological sampling. Also, prompt administration of broad-spectrum antimicrobial therapy is warranted, with the addition of clindamycin for its effect on toxin production, both in empirical therapy, and in targeted therapy for monomicrobial group A streptococcal and clostridial NSTI. The role of immunoglobulins and hyperbaric oxygen therapy remains controversial., Implications: Close collaboration between intensive care, surgery, microbiology and infectious diseases, and centralization of care is fundamental in the approach to the severely ill patient with NSTI. As many aspects of management of these rare infections are supported by low-quality data only, multicentre trials are urgently needed., (Copyright © 2019 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Background: In this study, we primarily sought to assess the ability of flow cytometry to predict early clinical deterioration and overall survival in patients with sepsis admitted in the ED and ICU., Methods: Patients admitted for community-acquired acute sepsis from 11 hospital centers were eligible. Early (day 7) and late (day 28) deaths were notified. Levels of CD64 pos granulocytes, CD16 pos monocytes, CD16 dim immature granulocytes (IGs), and T and B lymphocytes were assessed by flow cytometry using an identical, cross-validated, robust, and simple consensus standardized protocol in each center., Results: Among 1,062 patients screened, 781 patients with confirmed sepsis were studied (age, 67 ± 48 years; Simplified Acute Physiology Score II, 36 ± 17; Sequential Organ Failure Assessment, 5 ± 4). Patients were divided into three groups (sepsis, severe sepsis, and septic shock) on day 0 and on day 2. On day 0, patients with sepsis exhibited increased levels of CD64 pos granulocytes, CD16 pos monocytes, and IGs with T-cell lymphopenia. Clinical severity was associated with higher percentages of IGs and deeper T-cell lymphopenia. IG percentages tended to be higher in patients whose clinical status worsened on day 2 (35.1 ± 35.6 vs 43.5 ± 35.2, P = .07). Increased IG percentages were also related to occurrence of new organ failures on day 2. Increased IG percentages, especially when associated with T-cell lymphopenia, were independently associated with early (P < .01) and late (P < .01) death., Conclusions: Increased circulating IGs at the acute phase of sepsis are linked to clinical worsening, especially when associated with T-cell lymphopenia. Early flow cytometry could help clinicians to target patients at high risk of clinical deterioration., Trial Registry: ClinicalTrials.gov; No.: NCT01995448; URL: www.clinicaltrials.gov., (Copyright © 2018 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Cyclosporine has shown promising results for mortality in patients with Stevens-Johnson syndrome/toxic epidermal necrolysis. However, available studies included only a small number of patients and did not include a validated and homogenous control group. We present the results from a retrospective monocentric study including 174 patients with Stevens-Johnson syndrome/toxic epidermal necrolysis during 2005-2016. Among them, 95 received cyclosporine (3 mg/kg/day) plus supportive care, and 79 received supportive care only. Both a traditional exposed/unexposed method and a propensity score-matching method were used to compare the progression of skin detachment between day 0 and day 5, the proportion of patients with cutaneous re-epithelialization starting on day 5 or mucosal re-epithelialization on day 10, the duration of progression, and the number of deaths between the two groups. None of these outcomes significantly favored cyclosporine, either by the exposed/unexposed method or the propensity score method. Acute renal failure affected more patients receiving cyclosporine (P = 0.05). Overall, the results of this epidemiological study did not show a beneficial effect of cyclosporine in patients with Stevens-Johnson syndrome/toxic epidermal necrolysis. They are discordant with those previously published. The large number of patients and the use of a propensity score method provide valuable insights. The main limitation of the study is the lack of randomization., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: Necrotizing fasciitis (NF) are rare and severe soft tissue infections associated with a high mortality rate. In order to assess the management of NF in French-speaking intensive care units (ICUs), we conducted a survey endorsed by the French Society of Anesthesia and Intensive Care (SFAR)., Study Design: Online self-administered survey., Methods: A link to an online survey was sent by email to 4620 anesthesiologists and/or intensivists and was available online from January to February 2014., Results: One hundred and seventy-five physicians (3.8%) who worked in 135 ICUs filled out the online survey. Among respondents, 42% reported having managed up to two patients with NF during the previous year; 59% and 72% of respondents reported not having a surgical and a medical specialist consultant, respectively. A delayed access to the operating room (OR) of more than 6hours was reported in 31% of cases and access to the OR was reported not to be routinely considered as a priority in 13% of cases. Only 17% of respondents reported that time to transfer to the OR was never a cause for delayed surgery. The main causes for delayed surgery were: delayed diagnosis (45%), delayed validation of surgical intervention (37%), and difficulty of access to the OR (8%). Finally, 83% of respondents estimated that creating dedicated multidisciplinary teams for managing NFs could lead to improving outcomes., Conclusion: This survey illustrates the heterogeneous management of NF in French-speaking ICUs and points out several logistical aspects that should be improved to reduce the time to the first surgical debridement., (Copyright © 2014 Société française d’anesthésie et de réanimation (Sfar). Published by Elsevier SAS. All rights reserved.)

Background: Diffuse alveolar hemorrhage (DAH) represents a diagnostic challenge of acute respiratory failure. Prompt identification of the underlying cause of DAH and initiation of appropriate treatment are required in order to prevent acute respiratory failure and irreversible loss of renal function. More than 100 causes of DAH have been reported. However, the relative frequency and the differential presentation of those causes have been poorly documented, as well as their respective prognosis., Methods: We retrospectively reviewed the charts of 112 consecutive patients hospitalized for DAH in a tertiary referral center over a 30-year period., Results: Twenty-four causes of DAH were classified into four etiologic groups: immune (n = 39), congestive heart failure (CHF; n = 33), miscellaneous (n = 26), and idiopathic DAH (n = 14). Based on this classification, clinical and laboratory features of DAH differed on hospital admission. Patients with immune DAH had more frequent pulmonary-renal syndrome (p < 0.001), extra-pulmonary symptoms (p < 0.01), and lower blood hemoglobin level than others (p < 0.001). Patients with CHF-related DAH were older and received more anticoagulant treatments than others (p < 0.05). Those with miscellaneous causes of DAH exhibited a shorter prodromal phase (p < 0.001) and had more frequent hemoptysis >200 mL (p < 0.05). Patients with idiopathic DAH had more bronchoalveolar lavage siderophages (p < 0.01). In-hospital mortality was 24.1%, ranging from 7.1% in patients with idiopathic DAH to 36.4% in those with CHF., Conclusions: Arbitrary classification of DAH in four etiologic groups gives the opportunity to underline distinct presentations and outcomes of various causes of DAH., (Copyright © 2012 Elsevier Ltd. All rights reserved.)