Background and objectives Antifungal treatment (AFT) for proven or probable invasive candidiasis (IC) is common in critically ill, immunocompromised patients. Early AFT de-escalation appears safe in unselected ICU patients, but has not been studied specifically amongst immunocompromised hosts. Methods This retrospective study was conducted in 19 ICUs in France between January 2019 and December 2024. All immunocompromised patients hospitalized in ICU for ≥5 days and treated with antifungals for a first proven or probable episode of IC were included. Early AFT de-escalation was defined as either spectrum reduction, i.e., a switch from an initial echinocandin or liposomal amphotericin B to fluconazole, or complete discontinuation of the initial antifungal, occurring within 5 days (day 1-5) of treatment initiation. The primary objective was to determine the incidence of early AFT de-escalation (censored at day 28 after initiation of AFT). Results 242 patients were analysed (median age 64 years, 64% males). Most patients (n=175, 72.3%) were treated empirically or pre-emptively for probable IC. Early AFT de-escalation occurred in 92 patients (38%, 95% confidence interval [CI] 31.9%-44.2%). AFT de-escalation consisted in spectrum reduction in 35.9%, and AFT discontinuation in 64.1% of cases. There was no difference in ICU mortality, ICU length-of-stay and the number of ventilator-free days between patients with and without AFT de-escalation. AFT was re-initiated within 7 days of de-escalation in 6 over 92 patients (6.5%) who had undergone AFT de-escalation. Conclusions Early AFT de-escalation occurred in 38% of critically ill immunocompromised patients, and was not associated with adverse prognostic outcomes.(240 words).

Legionella is the second cause of community-acquired pneumonia in Intensive Care Unit (ICU) patients. The aim of this study was to describe the epidemiology and outcome in patients with Legionella pneumonia (LP) in French ICUs. A multi-center, retrospective, observational study in 12 French ICUs was performed between January 2014 and December 2019. LP was diagnosed in 162 patients during the study period. Invasive mechanical ventilation was required in 95 patients (58

BACKGROUND:Pneumocystis jirovecii pneumonia (PJP) is a life-threatening disease. In the intensive care unit (ICU), PJP is most frequently observed among patients with several conditions not related to the human immunodeficiency virus (HIV) infection. METHODS:The primary objective of the present post-hoc analysis of a multicenter, multinational, retrospective study was to assess factors impacting prognosis in ICU patients with PJP through univariable and multivariable analyses. RESULTS:A total of 107 patients were included; 28 had proven PJP (26.2%), and 79 had presumptive PJP (73.8%). The overall 30-day mortality was 52.7% (95% confidence interval [CI] 42.1-62.2). In the multivariable analysis, metastatic solid tumor (hazard ratio [HR] 3.49; 95% CI 1.71-7.13, p < 0.001) and chronic liver disease (HR 2.44; 95% CI 1.03-5.80, p = 0.044) showed an independent association with 30-day mortality. The direction of effect remained consistent when center was added to the multivariable model as random effect. CONCLUSION:PJP mortality remains high in ICU patients. Conditions other than HIV infection are emerging not only as non-classical risk factors for PJP development, but also as important mortality predictors. A better understanding of the reasons underlying this evolving landscape could be crucial to improve PJP management and survival.

Self-extubation is a common complication in intubated patients in the intensive care unit (ICU) and is associated with a high rate of reintubation. This study aimed to identify predictors of reintubation following self-extubation (SE) and assess the prognosis of these patients. Data were extracted from the French ICU database, OutcomeRea™. The primary objective was to identify factors associated with reintubation within 48 h after self-extubation. Secondary objectives included evaluating the association between reintubation and mortality, ICU length of stay, and nosocomial pneumonia. Between November 1996 and May 2022, 12,917 patients were intubated in the ICU. Among them, 701 patients experienced SE without therapeutic limitations at the time, and 276 (39.4

Background Non-ventilator-associated ICU-acquired pneumonia (NV-ICU-AP), a nosocomial pneumonia that is not related to invasive mechanical ventilation (IMV), has been less studied than ventilator-associated pneumonia, and never in the context of patients in an ICU for severe acute exacerbation of chronic obstructive pulmonary disease (AECOPD), a common cause of ICU admission. This study aimed to determine the factors associated with NV-ICU-AP occurrence and assess the association between NV-ICU-AP and the outcomes of these patients. Methods Data were extracted from the French ICU database, OutcomeRea™. Using survival analyses with competing risk management, we sought the factors associated with the occurrence of NV-ICU-AP. Then we assessed the association between NV-ICU-AP and mortality, intubation rates, and length of stay in the ICU. Results Of the 844 COPD exacerbations managed in ICUs without immediate IMV, NV-ICU-AP occurred in 42 patients (5%) with an incidence density of 10.8 per 1,000 patient-days. In multivariate analysis, prescription of antibiotics at ICU admission (sHR, 0.45 [0.23; 0.86], p = 0.02) and no decrease in consciousness (sHR, 0.35 [0.16; 0.76]; p < 0.01) were associated with a lower risk of NV-ICU-AP. After adjusting for confounders, NV-ICU-AP was associated with increased 28-day mortality (HR = 3.03 [1.36; 6.73]; p < 0.01), an increased risk of intubation (csHR, 5.00 [2.54; 9.85]; p < 0.01) and with a 10-day increase in ICU length of stay (p < 0.01). Conclusion We found that NV-ICU-AP incidence reached 10.8/1000 patient-days and was associated with increased risks of intubation, 28-day mortality, and longer stay for patients admitted with AECOPD.

Background Pneumocystis jirovecii pneumonia (PJP) is an opportunistic, life-threatening disease commonly affecting immunocompromised patients. The distribution of predisposing diseases or conditions in critically ill patients admitted to intensive care unit (ICU) and subjected to diagnostic work-up for PJP has seldom been explored. Materials and methods The primary objective of the study was to describe the characteristics of ICU patients subjected to diagnostic workup for PJP. The secondary objectives were: (i) to assess demographic and clinical variables associated with PJP; (ii) to assess the performance of Pneumocystis PCR on respiratory specimens and serum BDG for the diagnosis of PJP; (iii) to describe 30-day and 90-day mortality in the study population. Results Overall, 600 patients were included in the study, of whom 115 had presumptive/proven PJP (19.2%). Only 8.8% of ICU patients subjected to diagnostic workup for PJP had HIV infection, whereas hematological malignancy, solid tumor, inflammatory diseases, and solid organ transplants were present in 23.2%, 16.2%, 15.5%, and 10.0% of tested patients, respectively. In multivariable analysis, AIDS (odds ratio [OR] 3.31; 95% confidence interval [CI] 1.13–9.64, p = 0.029), non-Hodgkin lymphoma (OR 3.71; 95% CI 1.23–11.18, p = 0.020), vasculitis (OR 5.95; 95% CI 1.07–33.22, p = 0.042), metastatic solid tumor (OR 4.31; 95% CI 1.76–10.53, p = 0.001), and bilateral ground glass on CT scan (OR 2.19; 95% CI 1.01–4.78, p = 0.048) were associated with PJP, whereas an inverse association was observed for increasing lymphocyte cell count (OR 0.64; 95% CI 0.42–1.00, p = 0.049). For the diagnosis of PJP, higher positive predictive value (PPV) was observed when both respiratory Pneumocystis PCR and serum BDG were positive compared to individual assay positivity (72% for the combination vs. 63% for PCR and 39% for BDG). Cumulative 30-day mortality and 90-day mortality in patients with presumptive/proven PJP were 52% and 67%, respectively. Conclusion PJP in critically ill patients admitted to ICU is nowadays most encountered in non-HIV patients. Serum BDG when used in combination with respiratory Pneumocystis PCR could help improve the certainty of PJP diagnosis.

Herpes simplex virus 2 (HSV-2) rarely causes severe disease, even in solid organ transplant recipients. This paper describes a fatal case of HSV-2 infection, probably transmitted from a donor to a kidney transplant recipient. The donor was seropositive for HSV-2 but not for HSV-1, whereas the recipient was seronegative for both viruses before transplantation, suggesting that the graft was the source of infection. The recipient received valganciclovir prophylaxis due to cytomegalovirus seropositivity. Three months after transplantation, the recipient presented with rapidly disseminated cutaneous HSV-2 infection with meningoencephalitis. The HSV-2 strain was resistant to acyclovir, probably acquired under valganciclovir prophylaxis. Despite early initiation of acyclovir therapy, the patient died. This fatal case of HSV-2 infection, probably transmitted by the kidney graft with acyclovir-resistant HSV-2 from the onset, is uncommon.

Background COVID-19 severity is mainly related to lung impairment. However, preexisting patient characteristics and biomarkers at admission associated with this event are not precisely known.Methods We report 205 patients admitted for a proven COVID-19 in our institution between March 7 and April 22, 2020, particularly their comorbidities, respiratory severity, immune profile, and metabolic profile.Findings Median age was 70 years [interquartile range (IQR) 25-75: 60;79]; 115 (56·1%) patients were men. Oxygen supplementation of >2L/min was required in 107 patients (52·2%) after a median time of 8 days [IQR: 6;10] after the first symptoms; 67 (32·7%) patients were admitted to the intensive care unit (ICU), almost exclusively due to severe hypoxia. Patients requiring >2L/min oxygen therapy and/or ICU admission were older and more frequently males, with a significantly higher body mass index (BMI), a significantly higher total cholesterol (TC) / HDL cholesterol ratio, and higher triglycerides. They also had higher plasma levels of C-reactive protein (CRP) and interleukin 6 (IL-6); IL-6 >20 ng/L and CRP >70 mg/L were significantly associated with ICU admission and/or (for patients with a decision of limitation of life-support therapy) death. Higher BMI and TC/HDL-c ratio were associated with higher CRP and IL-6 levels. Steroid therapy was performed in 61 patients; while its clinical impact was inconclusive due to heterogeneous situations, IL-6 levels decreased significantly more in these patients.Interpretation Severe COVID-19 mostly relates to late-onset pneumonia associated with preexisting metabolic syndrome markers and a surge in inflammatory markers, allowing the early identification of at-risk patients.Funding This work was supported by Foundation University of Grenoble Alpes.### Competing Interest StatementThe authors have declared no competing interest.### Funding StatementThis work was supported by the Foundation University of Grenoble Alpes and Foundation Air Liquide.### Author DeclarationsI confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.YesThe details of the IRB/oversight body that provided approval or exemption for the research described are given below:This study was conducted in accordance with the French legislation on the retrospective use of healthcare data, and ethical approval was given by the Clinical Research Direction of the Centre Hospitalier Universitaire Grenoble-Alpes. The BIOMARCOVID project is a research project that does not involve the human being and whose controller is the Centre Hospitalier Grenoble Alpes. This research has been registered in accordance with French regulations and meets the requirements of the National Commission for Information Technology and Civil Liberties (CNIL La Commission Nationale de l'Informatique et des Libertes) reference methodology 004.I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).YesI have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.YesAll data produced in the present study are available upon reasonable request to the authors

Nous rapportons le cas d'un homme de 43 ans admis en unité de soins intensifs pour une leptospirose grave. Aprés une évolution favorable, le patient a développé une double infection fongique (abcés cérébral à Scedosporium apiospermium et mucormycose disséminée) probablement déclenchée par l'immunosuppression induite par le sepsis lié à la leptospirose.

Giant cell arteritis (GCA) is the most frequent systemic vasculitis occurring in adults older than 50 years, and aortitis is described in 40% to 80% of patients. The treatment relies on corticosteroids, but it is complicated by high rates of relapses and adverse effects and may be unable to completely inhibit aortic inflammation. Moreover, most of the current data regarding the pathophysiology of GCA have been obtained from bioassays using blood and temporal arteries, as well as histological analyses of temporal arteries and very few aortic aneurysms from patients with GCA. The limitations of these analyses prevent researchers from determining the implications of specific targets and studying the effects of targeted treatments. Several experimental models have been developed, but to date, a perfect model is not available for GCA, particularly for studies of large-vessel vasculitis. The review focuses on the perspectives on experimental models and new therapeutic targets in giant cell arteritis.

Objective: To characterize levamisole-induced vasculopathy. Methods: We performed a systematic review searching MEDLINE for articles published from 1972 to 2016. Results: We retrieved 357 references and abstracts and selected 111 articles. Levamisole-induced vasculopathy was reported in 192 patients, with a female predominance (n = 122, 63.5%). Median [interquartile range] age was 44 [38-50]. Skin was the most frequently involved organ (n = 182, 94.8%). Cutaneous lesions were mostly on the face (n = 136, 70.8%), especially the ears. Purpura (n = 131, 68.2%) was the most reported cutaneous lesion. Organ involvement included acute renal failure (n = 24, 12.5%), and pulmonary involvement (n = 20, 10.4%). Anti-neutrophil cytoplasmic antibodies (ANCAs) were found in 167/178 patients (93.8%), with both anti-myeloperoxydase and anti-proteinase 3 specificity reported in 51/118 patients (43.2%). Antiphospholipid (APL) antibodies were found in 93/137 patients (67.9%). Leukopenia was detected in 69/138 patients (50%). Skin biopsies identified vasculitis and thrombotic vasculopathy in 73/148 (49.3%) and 62/148 (41.9%) patients, respectively. The outcome was favourable in 116/134 patients (86.6%), but relapses were reported in 33 (28.4%), mainly on levamisole re-exposure. Conclusion: Levamisole-induced vasculopathy is characterized by a female predominance, skin involvement, ANCA and/or APL antibody positivity, leukopenia, vasculitis or vascular thrombotic histological lesions, and despite possible systemic involvement, a favourable outcome with levamisole interruption. (C) 2018 Published by Elsevier Inc.

Hepatitis E virus infection - mainly genotype 3 - is increasingly common in industrialized countries. Infection is usually asymptomatic, but cases of central or peripheral neurological symptoms with hepatitis E have been described. The most frequent is Guillain-Barre but somes cases of neuralgic amyotrophy have been described. In our center, since 2010, we have identified five cases of neuralgic amyotrophy associated with acute hepatitis E in immunocompetent patients. For all these patients, neuralgic amyotrophy was diagnosed with electromyogram and positive IgM for hepatitis E, and detectable HEV RNA in 4 of the cases. Including our patients, we count 26 cases in literature. The mean age of the patients was 44 years old, with a large predominance of males (88%). The disorder is bilateral and asymmetric in 69% of cases. Peripheral nerves other than the brachial plexus were affected in 6 patients (23%). In industrialized countries, any neuralgic amyotrophy, particularly if there is bilateral, asymmetric associated with involvement of nerves outside the brachial plexus, should lead physicians to consider a diagnosis of acute hepatitis E. (C) 2015 Elsevier B.V. All rights reserved.