Abstract Background Suspected invasive pulmonary aspergillosis (IPA) is increasingly treated in intensive care, including in patients without classical immunosuppression. Whether current research definitions (EORTC/MSGERC, FUNDICU) classify treated cases and predict mortality is unclear. Methods We retrospectively included adults in 48 French intensive care units who received systemic antifungal therapy for suspected IPA (January 2022-July 2024). Patients were categorized as having modified EORTC/MSGERC probable IPA, FUNDICU probable IPA, or unclassified. Ninety-day mortality was analyzed using multivariable Cox regression; heterogeneity was explored with unsupervised clustering. Results Among 371 treated patients, 217 (58%) met modified EORTC, 83 (22%) met FUNDICU, and 71 (19%) were unclassified. Overall, 90-day mortality was 62% and survival did not differ by category (63%, 63%, 58%; log-rank p=0.24). In adjusted analyses, IPA categorization was not associated with mortality (FUNDICU vs EORTC: adjusted hazard ratio (aHR)=0.86, 95% CI 0.62-1.20; unclassified vs EORTC: aHR=0.89, 0.62-1.30). Age (aHR 1.03/year, 1.02-1.05), SOFA (1.06/point, 1.03-1.10), and frailty (1.17/point, 1.07-1.30) independently predicted 90-day mortality. Exploratory clustering identified six phenotypes with 90-day mortality ranging from 40% to 80%. Conclusions Nearly one in five intensive care patients treated for suspected IPA were not classifiable by EORTC/MSGERC or FUNDICU definitions. Mortality was more strongly associated with age, frailty and acute severity than with classification category, supporting ICU-focused diagnostic frameworks and risk stratification; these associations should be read in light of the treatment-based design and do not establish that the definitions lack diagnostic value.

Background:Suspected invasive pulmonary aspergillosis (IPA) is increasingly treated in intensive care, including in patients without classical immunosuppression. Whether current research definitions (European Organization for Research and Treatment of Cancer [EORTC]/Mycoses Study Group Education and Research Consortium (MSGERC), Invasive Fungal Diseases in Adult Patients in ICU [FUNDICU]) classify treated cases and predict mortality is unclear. Methods:We retrospectively included adults in 48 French intensive care units who received systemic antifungal therapy for suspected IPA (January 2022 to July 2024). Patients were categorized as having modified EORTC/MSGERC probable IPA, FUNDICU probable IPA, or unclassified. Ninety-day mortality was analyzed using multivariable Cox regression; heterogeneity was explored with unsupervised clustering. Results:Among 371 treated patients, 217 (58%) met modified EORTC, 83 (22%) met FUNDICU, and 71 (19%) were unclassified. Overall, 90-day mortality was 62% and mortality did not differ by category (63%, 63%, 58%; log-rank P = .24). In adjusted analyses, IPA categorization was not associated with mortality (FUNDICU vs EORTC: adjusted hazard ratio [aHR] = 0.86, 95% CI .62-1.20; unclassified vs EORTC: aHR = 0.89, .62-1.30). Age (aHR 1.03/year, 1.02-1.05), Sequential Organ Failure Assessment (1.06/point, 1.03-1.10), and frailty (1.17/point, 1.07-1.30) independently predicted 90-day mortality. Exploratory clustering identified 6 phenotypes with 90-day mortality ranging from 40% to 80%. Conclusions:Nearly 1 in 5 intensive care patients treated for suspected IPA were not classifiable by EORTC/MSGERC or FUNDICU definitions. Mortality was more strongly associated with age, frailty, and acute severity than with classification category, supporting ICU-focused diagnostic frameworks and risk stratification; these associations should be read in light of the treatment-based design and do not establish that the definitions lack diagnostic value.

Infection are the leading cause of intensive care unit (ICU) admission, yet conventional microbiological methods frequently fail to identify the causative pathogen. Metagenomic next-generation sequencing (mNGS) is an emerging, unbiased, pan-pathogen diagnostic tool. However, its real-world microbiological and clinical impact in the ICU remains poorly characterized. This study aimed to assess the microbiological yield and clinical impact of mNGS when implemented in routine ICU practice. This retrospective multicenter study was conducted across ten tertiary-care ICUs in the Greater Paris area between January 2018 and April 2024. All patients for whom an mNGS analysis was requested by clinicians from a microbiological sample were included. Any additional pathogens identified by mNGS were independently classified as causative, possibly causative, or non-causative by two reviewers. The independent reviewers also categorised therapeutic changes attributable to mNGS as escalation, de-escalation, discontinuation, or other decision support. Discrepancies were adjudicated by a third reviewer. A total of 144 mNGS analyses were performed in 132 critically ill patients (median age 55 years), 31

To assess whether skin blood flow (SBF) monitoring combined with passive leg raising (PLR) can predict microvascular fluid responsiveness in septic patients. Prospective observational study. Single-center, 18-bed medical ICU in a tertiary university hospital in Paris, France. Adult patients with sepsis requiring intravenous fluid administration. Patients underwent a standardized PLR maneuver followed by a 500 mL saline fluid administration. Peripheral SBF was continuously monitored by fingertip laser Doppler flowmetry. Of 37 patients included, 27 (73

Background: Emphysematous pyelonephritis (EPN) is a rare, life-threatening necrotizing urinary tract infection marked by gas formation in the renal parenchyma and perirenal tissues. Evidence on its management and outcomes in the intensive care unit (ICU) remains limited. We aimed to describe the clinical profile, outcomes, and effect of nephrectomy in adults admitted to the ICU for infectious EPN. Main results: A national, multicenter, retrospective cohort study including adults admitted with infectious EPN to 48 French ICUs from 2001 to 2021 was conducted. A total of 109 patients were included. Median age was 62 years [IQR 54–72], and 64% were women. Overweight or obesity was present in 74%, and diabetes in 63%. Septic shock occurred in 72%. Urinary tract obstruction was identified in 46%. Initial management relied on antibiotics and/or minimally invasive drainage in 53% of cases. Early nephrectomy (≤24 h after ICU admission) was performed in 14 patients (14%), and delayed nephrectomy in eight (7%) at a median of 4 days [IQR 3–9]. Among the 75 patients discharged from the ICU without nephrectomy, four (4%) required subsequent nephrectomy. ICU mortality was 15% (n = 16). At day 90, vital status was known for 105 patients; 18 had died. In multivariable analysis, higher Simplified Acute Physiology Score II independently predicted increased 90-day mortality (HR per point 1.08; 95% CI 1.05–1.12; p < 0.001). Early nephrectomy was associated with lower mortality (HR 0.18; 95% CI 0.04–0.90; p = 0.037). Major adverse kidney events at day 90 occurred in 40%. Using the propensity-weighted model, early nephrectomy showed a trend toward lower MAKE90, although the association did not reach statistical significance (adjusted OR = 0.32; 95% CI: 0.10–1.02; p = 0.054). Conclusion: EPN requiring ICU admission carries substantial mortality. Early nephrectomy may improve survival, without increasing long-term renal complications.

BACKGROUND:Invasive meningococcal disease (IMD) is traditionally associated with younger populations, but its impact on older adults is rising. We aimed to describe the clinical characteristics and outcomes of critically ill older patients with IMD and identify risk factors for in-hospital mortality. METHODS:We conducted an ancillary analysis of the French nationwide multicenter RETRO-MENINGO cohort (2016-2024). All adults admitted to 102 ICUs with microbiologically confirmed IMD were included and stratified by age (≥65 vs. <65 years). The primary outcome was all-cause in-hospital mortality. Multivariable logistic regression identified factors independently associated with death. RESULTS:Among 654 patients, 114 (17%) were aged ≥65 years, of whom only 0.9% were reported as vaccinated. Compared to younger adults, older patients presented more frequently with hemodynamic failure and less often with classic purpura or meningeal symptoms. Serogroup W predominated in the older group, while serogroup B was more common in younger patients. Older adults required more organ support and had significantly higher in-hospital mortality (28.1%, n=32/114 vs. 9.6%, n=52/540 p<0.001). After adjustment, age ≥65 years remained independently associated with in-hospital mortality (aOR 2.99; 95% CI 1.57-5.72; p<0.001), while administration of a third-generation cephalosporin before ICU admission was protective (aOR 0.45; 95% CI, 0.24-0.84; p=0.01). CONCLUSIONS:Critically ill older adults with IMD exhibit atypical clinical features, a high prevalence of serogroup W, and nearly triple the in-hospital mortality of younger patients. These findings emphasize the need for high clinical suspicion, rapid antibiotic therapy, and potential expansion of vaccination strategies to include older populations.

Invasive meningococcal disease (IMD) is a rare but potentially fatal infection caused by Neisseria meningitidis. In adults requiring admission to intensive care unit (ICU), IMD typically presents with two distinct clinical presentations: neurological (meningitis) and hemodynamic (sepsis). These presentations are often conflated, despite the differences in pathophysiology and outcome. RETRO-MENINGO is a nationwide, multicentre, retrospective cohort study conducted in 102 French ICUs between January 1, 2016, and December 31, 2024. Adults (≥ 18 years) admitted to the ICU with a microbiologically confirmed IMD were categorised as having either a neurological or a hemodynamic presentation according to the main reason for ICU admission. The primary outcome was day-60 mortality in each presentation. Of 654 patients (median age 33 years [IQR 21–56]; 63.5

Capillary refill time (CRT) and skin blood flow (SBF) have been reported to be strong predictors of mortality in critically ill patients. However, the relationship between both parameters remains unclear. We conducted a prospective observational study in a tertiary teaching hospital. All patients older than 18 years admitted in the intensive care unit (ICU) with circulatory failure and a measurable CRT were included. We assessed index SBF by laser doppler flowmetry and CRT on the fingertip, at T0 (Within the first 48 h from admission) and T1 (4 to 6 h later). Correlation was computed using Spearman or Pearson’s formula. During a 2-month period, 50 patients were included, 54

Enterococcal infections represent 10

Autonomic nervous system (ANS) dysfunction contributes to the pathophysiology of sepsis. However, studies using reliable methods for ANS activity monitoring and evaluating its association with outcomes in sepsis patients are scarce. The Sudoscan® device offers a non-invasive method to evaluate sympathetic function by measuring electrochemical skin conductance (ESC), but its clinical relevance in sepsis remains unclear. This study aimed to assess autonomic sympathetic activity in septic patients using the Sudoscan® technology and explore its relationship with peripheral perfusion and outcomes. This prospective, observational, single-center study included 97 consecutive adult ICU septic patients without or with shock. Sudoscan® measurements were performed at admission and serially for 72 h, alongside standard hemodynamic and peripheral perfusion assessments (e.g., knee capillary refill time [CRT], mottling, cardiac output). Associations between ESC ("sudoscore"), clinical parameters, and mortality at day-28 were analyzed. Of the 97 septic patients included, 37

Autoimmune hemolytic anemia (AIHA) is a rare but potentially life-threatening condition requiring intensive care unit (ICU) admission in severe cases. While corticosteroids and immunosuppressants are standard treatments, their delayed efficacy limits their utility in critical settings requiring rapid hemolysis control. Plasma exchange (PlEx) may offer a rapid intervention, but its effectiveness in severe AIHA remains uncertain. This study aims to assess the clinical characteristics, outcomes, and the potential benefit of PlEx in ICU cases with severe AIHA. We conducted a multicenter retrospective cohort study including patients with severe AIHA admitted to 15 ICUs within the Assistance Publique–Hôpitaux de Paris (AP-HP) network between 2017 and 2024. Clinical, biological, and therapeutic data were collected. A multivariate logistic regression model, an analysis adjusted on a propensity score (PS) and on inverse probability of treatment weighting (IPTW) were used to identify predictors of in-ICU mortality and evaluate the association between PlEx and in-ICU mortality. One hundred forty-eight ICU stays involving severe AIHA hemolytic crises were analyzed. The median age at ICU admission was 61 48–71 years, with a balanced sex ratio (51

Current triplet regimens associating therapeutic plasma exchange (TPE), immunosuppression with corticosteroids and rituximab, and caplacizumab have dramatically improved the outcome of immune-mediated thrombotic thrombocytopenic purpura (iTTP). However, nearly half of the patients require extended caplacizumab treatment (i.e., > 30 days) due to persistent ADAMTS13 deficiency, raising cost and tolerance concerns. Therefore, we investigated whether anti-ADAMTS13 antibodies titer and their trajectory during the acute phase of the disease could predict ADAMTS13 improvement (i.e., activity ≥ 20% before day-30 post-TPE). From a cohort of 286 patients receiving the triplet regimen, we identified on diagnosis a cut-off value for anti-ADAMTS13 IgG antibodies of 90.5 U/mL, with a modest discriminating ability (AUC: 0.57) for predicting long-term response, precluding its use to guide therapeutic strategies. Nonetheless, the analysis of anti-ADAMTS13 IgG antibodies titer trajectory from diagnosis revealed that the proportion of iTTP patients with ADAMTS13 activity improvement was higher in patients who decreased (Dec+) their antibodies titer within the 7-14 days interval post-TPE compared to those without decrease (Dec-) (65% vs. 25% of cases, respectively, p < 0.001), a finding confirmed in a validation cohort (N = 51). These results highlight the possibility of intensifying immunosuppression in an early period post-TPE to shorten time to ADAMTS13 activity recovery. Close monitoring of anti-ADAMTS13 antibodies titer may guide immunomodulation strategies, including additional courses of B-cell depleting agents when appropriate.

OBJECTIVES:COVID-19 has been associated with high rates of ventilator-associated pneumonia relapse. Antibiotic underdosing due to augmented renal clearance (ARC) has been suggested as a possible contributing factor. This retrospective study compared plasmatic beta-lactam concentrations between critically-ill COVID-19 and non-COVID-19 patients. PATIENTS AND METHODS:We included measurements for cefotaxime, ceftazidime, cefepime and piperacillin. A multivariable logistic regression model was used to identify variables associated with underdosing. RESULTS:All in all, 361 samples were included from 126 patients. Median concentrations did not differ between COVID-19 and non-COVID-19 patients for any molecule, nor did the rate of underdosing (38 % vs 42 %, p = 0.68). In a logistic regression model adjusting for age, gender, BMI, creatinine clearance and type of beta-lactam molecule, COVID-19 status was not associated with underdosing (OR = 0.83 [0.38-1.83], p = 0.997). CONCLUSIONS:Although underdosing of most commonly prescribed beta-lactams occurred in more than one third of cases in critically-ill COVID-19 patients, this rate did not differ from non-COVID-19 patients.

Invasive group A streptococcus (iGAS) infection incidence is rising. These infections have been studied as a whole but can be associated with critical illness in a population with a wide array of underlying conditions, sites of infection and clinical presentations. Using an unsupervised clustering approach, we aimed to identify specific clinical phenotypes regarding presentation, management and outcome. This was a retrospective multicentric study including all patients admitted to one of 9 ICUs of Paris University Hospitals for an iGAS infection between 01/03/2018 and 01/08/2023. iGAS infection was defined as GAS growth in any microbiological sample from a sterile site. Patients were grouped according to a clustering algorithm (k-prototypes) using a comprehensive set of clinical and biological variables available upon ICU admission. Clusters were described and clinical presentation, management and outcome were compared. 148 patients were included. According to the Silhouette criterion, patients were grouped in 3 clusters, and 7 patients remained unclassified. Cluster 1 (n = 73) comprised a greater proportion of less severely-ill female patients with painful skin and soft tissue infections, a quarter of whom had taken non-steroidal anti-inflammatory drugs. Cluster 2 (n = 42) was characterized by a high rate of respiratory infections with frequent viral co-infections. Cluster 3 (n = 26) included mostly socially deprived patients with high rates of chronic alcohol consumption and psychiatric illness, with severe organ dysfunction related to otherwise pauci-symptomatic skin and soft tissue infections. There was no significant difference in time to source control across clusters (0 [0–0] vs 0 [0–0] vs 0 [0–1] days, p = 0.12). Patients included in cluster 2 less frequently received antitoxin antibiotics than patients from clusters 1 and 3 (79

Monoclonal gammopathy-associated capillary leak syndrome (MG-CLS) is a rare condition characterized by recurrent episodes of hypovolemic shock caused by a sudden increase in capillary permeability. The COVID-19 pandemic has been associated with a rise in MG-CLS episodes and increased mortality. We aimed to explore the association between MG-CLS and SARS-CoV-2 infection. We conducted a multicenter retrospective observational study involving MG-CLS patients who were admitted to the intensive care unit (ICU). The primary endpoint was 28-day mortality according to whether SARS-CoV-2 was identified as a trigger. The study included 84 patients (44

Background Necrotizing soft tissue infections (NSTI) are rare and life-threatening bacterial infections characterized by necrosis of subcutaneous tissue, fascia, or muscle. Few prospective studies have been conducted. The primary objective is to assess the 90-day mortality rate and to identify prognostic factors in patients with NSTI in an international setting. Secondary objectives are i) to characterize the clinical and microbiological presentation and management; ii) to assess the risk of limb amputation and associated factors; and iii) to assess functional and health-related quality of life (HRQoL) outcomes and associated factors. Methods We are conducting a multinational, prospective, non-interventional cohort study. We plan to enroll 1,033 consecutive patients admitted to 85 hospitals with surgically proven NSTI between November 2021 and December 2024 in 17 countries over three continents. Data will be collected prospectively on a secure web-based server. The primary outcome measure will be the day-90 mortality. Secondary outcomes include need for limb amputation, the activity of daily living scale and health-related quality of life at day-90 (EQ-5D-5L questionnaire). Baseline characteristics associated with outcomes will be identified by multivariable analyses. Exploratory analyses will be conducted to assess the impact of therapeutic interventions on day-90 mortality and secondary outcomes. The study protocol has been approved by an ethics committee in each participating country.

Necrotizing soft tissue infections (NSTIs) are uncommon, yet rapidly progressive and potentially fatal conditions. However, evidence-based guidance on antibiotic therapy remains limited. Current recommendations emphasize the need for broad-spectrum empirical coverage, including gram-positive, gram-negative, anaerobes, and Streptococcus pyogenes when clinically indicated. We aimed at developing a practical, evidence-based framework for empirical antibiotic therapy in NSTIs. This narrative review is informed by a comprehensive literature search of PubMed, without date restrictions. We propose a structured decision-making algorithm for empirical antibiotic selection in NSTIs, integrating key clinical parameters: infection site, healthcare-associated versus community-acquired origin, risk factors for extended-spectrum β-lactamase-producing Enterobacterales and methicillin-resistant Staphylococcus aureus, and signs of sepsis or septic shock. Alternative regimens are provided for patients with severe β-lactam allergies. Special considerations for immunocompromised and other vulnerable host populations are also addressed. This review offers clinicians a pragmatic, stepwise approach to antibiotic therapy in NSTIs, while identifying critical knowledge gaps and priorities for future research.

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. CHEST 2024; 165(1):48-57

A 48-year-old patient received chimeric antigen receptor (CAR)-T cell therapy for relapsed diffuse large-B cell lymphoma with central nervous system involvement. He had no sign of active disease at the time of CAR-T cell infusion, after being treated with Rituximab, Ifosfamide, Carboplatine, Etoposide (R-ICE) for left capsulolenticular and temporal lesions responsible for right-facial paralysis. Two days after CAR-T cell infusion (Axicabtagene-ciloleucel), the patient became febrile and four days after infusion he received Tocilizumab given that persistent fever. The daily dysgraphia evaluation as well as immune effector cell-associated encephalopathy (ICE) Score and neurological exam had been normal until day 6, when slight difficulties in writing the usual sentence appeared (Figure 1). This progressive dysgraphia was followed by more overt neurological deterioration with confusion, aphasia, and diffuse hyperreflexia. ICE-score decreased from 10 to 6, Immune effector cell-associated neurotoxicity syndrome (ICANS) grade 2 was suspected. On day 7, the patient could not write and the ICE score was 0 with grade 3 ICANS. Echolalia with apraxia appeared and aphasia worsened. Electroencephalogram revealed encephalopathy and brain magnetic resonance imaging ruled out encephalitis, edema, bleeding, or lymphoma progression. Cerebrospinal fluid examination revealed 6 leukocytes/mm3 and elevated proteinorachia (3.39 g/L). The patient received high-dose Dexamethasone (10 mg every 6 h) plus Anakinra (200 mg every 8 h) and, on the following day, could only write a single word repeatedly. 48 h after the treatment he could normally write the complete sentence again and the ICE score was 10. While paraclinical exams might help to manage treatment response in complex patients, clinicians should stay aware that early diagnosis and follow-up can rely on simple clinical findings such as handwriting. All authors took care of the patient. Vincent Bonny wrote the first draft of the manuscript. All authors read and approved the final manuscript. The authors declare no conflict of interest. The authors have confirmed ethical approval statement is not needed for this submission. The authors have confirmed patient consent statement is not needed for this submission. The authors have confirmed clinical trial registration is not needed for this submission. The data that support the findings of this study are available on request from the corresponding author.