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Managing patients with acute respiratory distress syndrome (ARDS) requires frequent changes in mechanical ventilator respiratory settings to optimize arterial oxygenation assessed by arterial oxygen partial pressure (PaO 2 ) and saturation (SaO 2 ). Pulse oxymetry (SpO 2 ) has been suggested as a non-invasive surrogate for arterial oxygenation however its accuracy in COVID-19 patients is unknown. In this study, we aimed to investigate the influence of COVID-19 status on the association between SpO 2 and arterial oxygenation. We prospectively included patients with ARDS and compared COVID-19 to non-COVID-19 patients, regarding SpO 2 and concomitant arterial oxygenation (SaO 2 and PaO 2 ) measurements, and their association. Bias was defined as mean difference between SpO 2 and SaO 2 measurements. Occult hypoxemia was defined as a SpO 2  ≥ 92% while concomitant SaO 2  < 88%. Multiple linear regression models were built to account for confounders. We also assessed concordance between positive end-expiratory pressure (PEEP) trial-induced changes in SpO 2 and in arterial oxygenation. We included 55 patients, among them 26 (47%) with COVID-19. Overall, SpO 2 and SaO 2 measurements were correlated (r = 0.70; p  < 0.0001), however less so in COVID-19 than in non-COVID-19 patients (r = 0.55, p  < 0.0001 vs. r = 0.84, p  < 0.0001, p  = 0.002 for intergroup comparison). Bias was + 1.1%, greater in COVID-19 than in non-COVID-19 patients (2.0 vs. 0.3%; p  = 0.02). In multivariate analysis, bias was associated with COVID-19 status (unstandardized β = 1.77, 95%CI = 0.38–3.15, p  = 0.01), ethnic group and ARDS severity. Occult hypoxemia occurred in 5.5% of measurements (7.7% in COVID-19 patients vs. 3.4% in non-COVID-19 patients, p  = 0.42). Concordance rate between PEEP trial-induced changes in SpO 2 and SaO 2 was 84%, however less so in COVID-19 than in non-COVID-19 patients (69% vs. 97%, respectively). Similar results were observed for PaO 2 regarding correlations, bias, and concordance with SpO 2 changes. In patients with ARDS, SpO 2 was associated with arterial oxygenation, but COVID-19 status significantly altered this association.

Acute respiratory distress syndrome (ARDS) related to Coronavirus disease (COVID-19) is associated with high mortality. It has been suggested that venovenous extracorporeal membrane oxygenation (ECMO) was suitable in this indication, albeit the effects of ECMO on the mechanical respiratory parameters have been scarcely described. In this case-series, we prospectively described the use of venovenous ECMO and its effects on mechanical respiratory parameters in eleven COVID-19 patients with severe ARDS. Implantation of ECMO occurred 6 [3–11] days after the onset of mechanical ventilation. At the time of ECMO implantation, all patients received neuromuscular blocking agents, three (27%) received inhaled nitric oxide and prone positioning was performed in all patients with 4 [3−5] sessions of PP per patient. Under ECMO, the tidal volume was significantly decreased from 6.1 [4.0–6.3] to 3.4 [2.5–3.6] mL/kg of predicted body weight and the positive end-expiratory pressure level was increased by 25 ± 27% whereas the driving pressure and the mechanical power decreased by 33 ± 25% and 71 ± 27%, respectively. The PaO 2 /FiO 2 ratio significantly increased from 68 [58–89] to 168 [137–218] and the oxygenation index significantly decreased from 28 [26–35] to 13 [10–15]. The duration of ECMO was 12 [8–25] days. Nine (82%) patients experienced ECMO-related complications and the main complication was major bleeding requiring blood transfusions. Intensive care unit mortality rate was 55% but no patient died from ECMO-related complications. In COVID-19 patients with severe ARDS, venovenous ECMO allowed ultra-protective ventilation, improved oxygenation and should be considered in highly selected patients with the most severe ARDS.

Candidemia displays significant clinical heterogeneity in critically ill patients. This study aimed to identify distinct clinical phenotypes and to assess their association with 90-day mortality. We conducted a multicenter retrospective cohort study of 492 intensive care unit (ICU) patients with candidemia from 16 French ICUs (2015-2023). We performed a factor analysis of mixed data (FAMD) incorporating both categorical and continuous baseline variables, followed by hierarchical clustering on principal components (HCPC). Survival analysis was performed with Kaplan-Meier curves and Cox proportional hazards models. Overall, 90-day mortality for the 492 patients (median age: 64 years, 69.1% male) with candidemia was 62.6%. Three different phenotypes emerged from FAMD followed by HCPC: Phenotype 1 (n = 70, 14.2%) comprised patients with severe immunosuppression, mostly due to hematological malignancies (82.9%), and high severity scores (SAPS II:70); Phenotype 2 (n = 223, 45.3%) corresponded to elderly cirrhotic patients (19.3%) with early-onset digestive candidemia; Phenotype 3 (n = 199, 40.5%) comprised younger patients with lower severity scores and catheter-related candidemia. Mortality differed significantly between phenotypes: 72.9% (Phenotype 1), 70.4% (Phenotype 2), and 50.3% (Phenotype 3) (p < 0.001). Independent predictors of mortality included age (aHR: 1.01, 95% CI: 1.00-1.02; p = 0.003), cirrhosis (aHR: 1.90, 95% CI: 1.39-2.60; p < 0.001), SAPS II (aHR: 1.01, 95% CI: 1.01-1.02; p < 0.001), echinocandin use (aHR = 0.49, 95% CI: 0.39-0.63; p < 0.001) and proven catheter-related candidemia (protective; aHR: 0.48, 95% CI: 0.33-0.69; p < 0.001). Immunodepression was not associated with mortality. Unsupervised clustering identified three clinically different candidemia phenotypes with different outcomes. Cirrhosis, higher age and illness severity were associated with mortality, whereas a catheter-related source of infection was protective.

Background Candidemia is a life-threatening fungal infection in intensive care unit (ICU) patients that can be complicated by secondary localization (SL). However, the prevalence, risk-factors, and outcomes of patients with secondary localization during candidemia remain poorly explored. Methods The CandidICU study was a retrospective multicenter cohort study conducted in 16 French ICUs. All adult patients hospitalized from 01-2015 to 01-2023 for candidemia were enrolled. We assessed the prevalence and risk-factors for SL. In addition, we explored the clinical course according to the screening and occurrence of SL. Results Among 492 patients hospitalized in ICU with at least one positive blood culture for Candida sp., 376 were screened for SL (76.4%). At least one SL was diagnosed in 82 patients (21.8%). Competing risk analysis identified the SAPSII score and the duration of positive blood cultures as independent risk factors for SL (sdHR 1.01 [95%CI 1.00-1.02]; p = 0.031 and sdHR 1.05 [95%CI 1.02−1.08]; p = 0.003, respectively). Age and Candida glabrata infection were protective factors against SL (sdHR 0.98 [95%CI 0.97−1.00]; p = 0.016 and sdHR 0.38 [95%CI 0.15-0.99]; p = 0.048, respectively). Finally, patients with SL received longer antifungal treatment (18 [11−30] versus 14 [6–18] days; p < 0.001) and had a higher rate of antifungal escalation (27.8% versus 12.3%; p = 0.002). Conclusions In this cohort, 76·4% of ICU patients with candidemia were screened for SL and at least one SL was diagnosed in 21·8%. The severity at ICU admission and duration of positive blood cultures were identified as independent risk factors for SL, whereas age and Candida glabrata infection were protective. Finally, the screening and occurrence of SL were associated with significant changes in the management of patients. Key points Secondary localization can occur in patients with candidemia in various sites: vascular (thrombosis), abdominal (notably hepatosplenic or renal), cardiac, ophthalmic, pulmonary, and/or osteo-articular, which influences the management of these critical patients.

Purpose Recent doubts regarding the efficacy may have resulted in a loss of interest for targeted temperature management (TTM) in comatose cardiac arrest (CA) patients, with uncertain consequences on outcome. We aimed to identify a change in TTM use and to assess the relationship between this change and neurological outcome. Methods We used Utstein data prospectively collected in the Sudden Death Expertise Center (SDEC) registry (capturing CA data from all secondary and tertiary hospitals located in the Great Paris area, France) between May 2011 and December 2017. All cases of non-traumatic OHCA patients with stable return of spontaneous circulation (ROSC) were included. After adjustment for potential confounders, we assessed the relationship between changes over time in the use of TTM and neurological recovery at discharge using the Cerebral Performance Categories (CPC) scale. Results Between May 2011 and December 2017, 3925 patients were retained in the analysis, of whom 1847 (47%) received TTM. The rate of good neurological outcome at discharge (CPC 1 or 2) was higher in TTM patients as compared with no TTM (33% vs 15%, P < 0.001). Gender, age, and location of CA did not change over the years. Bystander CPR increased from 55% in 2011 to 73% in 2017 ( P < 0.001) and patients with a no-flow time longer than 3 min decreased from 53 to 38% ( P < 0.001). The use of TTM decreased from 55% in 2011 to 37% in 2017 ( P < 0.001). Meanwhile, the rate of patients with good neurological recovery remained stable (19 to 23%, P = 0.76). After adjustment, year of CA occurrence was not associated with outcome. Conclusions We report a progressive decrease in the use of TTM in post-cardiac arrest patients over the recent years. During this period, neurological outcome remained stable, despite an increase in bystander-initiated resuscitation and a decrease in “no flow” duration.

This trial randomly assigned patients with coma after out-of-hospital cardiac arrest to undergo targeted hypothermia at 33°C or normothermia with treatment of fever. At 6 months, there were no significant between-group differences regarding death or functional outcomes.

Coronavirus disease 2019 (COVID-19) is a disease caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and has resulted in a pandemic 1 . The C5a complement factor and its receptor C5aR1 (also known as CD88) have a key role in the initiation and maintenance of several inflammatory responses by recruiting and activating neutrophils and monocytes 1 . Here we provide a longitudinal analysis of immune responses, including phenotypic analyses of immune cells and assessments of the soluble factors that are present in the blood and bronchoalveolar lavage fluid of patients at various stages of COVID-19 severity, including those who were paucisymptomatic or had pneumonia or acute respiratory distress syndrome. The levels of soluble C5a were increased in proportion to the severity of COVID-19 and high expression levels of C5aR1 receptors were found in blood and pulmonary myeloid cells, which supports a role for the C5a–C5aR1 axis in the pathophysiology of acute respiratory distress syndrome. Anti-C5aR1 therapeutic monoclonal antibodies prevented the C5a-mediated recruitment and activation of human myeloid cells, and inhibited acute lung injury in human C5aR1 knock-in mice. These results suggest that blockade of the C5a–C5aR1 axis could be used to limit the infiltration of myeloid cells in damaged organs and prevent the excessive lung inflammation and endothelialitis that are associated with acute respiratory distress syndrome in patients with COVID-19. Blockade of the C5a–C5aR1 axis using anti-C5aR1 monoclonal antibodies prevented inflammation associated with COVID-19.

Myeloablative doses of melphalan with rescue by autologous hematopoietic stem cells are currently used in the treatment of immunoglobulin-light-chain (AL) amyloidosis, but the efficacy of the therapy is unproven. This randomized trial compared a regimen of high-dose melphalan with standard doses of melphalan plus high doses of dexamethasone. The aggressive treatment had no survival advantage as compared with conventional treatment with standard-dose melphalan. This trial compared a regimen of high-dose melphalan with standard doses of melphalan plus high doses of dexamethasone. The aggressive treatment had no survival advantage as compared with conventional treatment. The origin of amyloid in systemic immunoglobulin-light-chain (AL) amyloidosis is a clone of plasma cells in the bone marrow that synthesizes monoclonal immunoglobulin light chains. In tissues, these light chains aggregate into amyloid fibrils. The accumulation of amyloid deposits in vital organs leads to progressive disability and death. Life expectancy depends on the degree of organ involvement and ranges from a few years to less than 6 months for patients with severe cardiomyopathy. 1 In the mid-1990s, two randomized trials showed that standard-dose chemotherapy with melphalan and prednisone could prolong survival in patients with AL amyloidosis, 1 , 2 but clinical responses were . . .

Leguminous plants (such as peas and soybeans) and rhizobial soil bacteria are symbiotic partners that communicate through molecular signaling pathways, resulting in the formation of nodules on legume roots and occasionally stems that house nitrogen-fixing bacteria. Nodule formation has been assumed to be exclusively initiated by the binding of bacterial, host-specific lipochito-oligosaccharidic Nod factors, encoded by the nodABC genes, to kinase-like receptors of the plant. Here we show by complete genome sequencing of two symbiotic, photosynthetic, Bradyrhizobium strains, BTAi1 and ORS278, that canonical nodABC genes and typical lipochito-oligosaccharidic Nod factors are not required for symbiosis in some legumes. Mutational analyses indicated that these unique rhizobia use an alternative pathway to initiate symbioses, where a purine derivative may play a key role in triggering nodule formation.