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Introduction: First-line oxygenation strategy in patients with acute hypoxaemic respiratory failure consists in standard oxygen or high-flow nasal oxygen therapy. Clinical practice guidelines suggest the use of high-flow nasal oxygen rather than standard oxygen. However, findings remain contradictory with a low level of certainty. We hypothesise that compared with standard oxygen, high-flow nasal oxygen may reduce mortality in patients with acute hypoxaemic respiratory failure., Method and Analysis: The Standard Oxygen versus High-flow nasal Oxygen-trial is an investigator-initiated, multicentre, open-label, randomised controlled trial comparing high-flow nasal oxygen versus standard oxygen in patients admitted to an intensive care unit (ICU) for acute respiratory failure with moderate-to-severe hypoxaemia. 1110 patients will be randomly assigned to one of the two groups with a ratio of 1:1. The primary outcome is the number of patients who died 28 days after randomisation. Secondary outcomes include comfort, dyspnoea and oxygenation 1 hour after treatment initiation, the number of patients intubated at day 28, mortality in ICU, in hospital and until day 90, and complications during ICU stay., Ethics and Dissemination: The study has been approved by the central Ethics Committee 'Sud Méditerranée III' (2020-07-05) and patients will be included after informed consent. The results will be submitted for publication in peer-reviewed journals., Trial Registration Number: NCT04468126., Competing Interests: Competing interests: J-PF reports grants from the French Ministry of Health; personal fees for lectures, travel expense coverage to attend scientific meetings, grant for randomised clinical trial from Fisher and Paykel Healthcare; personal fees as member of a scientific board and travel expense coverage to attend scientific meetings from SOS Oxygène outside this work. RC reports grants from the European Respiratory Society and the French Intensive Care Society, and travel expense coverage to attend scientific meetings from Fisher and Paykel Healthcare and MSD. SE discloses consultancies from Aerogen, research support, speaker fees and travel support from Aerogen and Fisher & Paykel Healthcare, research support from Open AI. AD reports grants from the French Ministry of Health, Assistance publique – Hôpitaux de Paris, Lungpacer, Respinor, consulting fees from Respinor, Lungpacer, Lowenstein, Tribunal administratif de Cergy, Liberate Medical, payment or honoraria for lectures, presentations from Fisher & Paykel, Baxter, Getinge, Astra, Agence Européenne Informatique, Mindray, support for attending meetings and/or travel from Lungpacer, outside the submitted work. GCarteaux reports personal fees from Air Liquide Medical System, GE Healthcare, Dräger, Fisher and Paykel, Medtronic and Löwenstein, outside the submitted work. FB reports consulting fees from Löwenstein Medical and Air Liquid Medical Systems and research support from Covidien and GE Healthcare outside this work. J-CR reports grant from Hamilton medical and travel expense coverage to attend scientific meetings from GILEAD and Pfizer. GH has received personal fees for lectures, travel expense coverage to attend scientific meetings from Fisher and Paykel Healthcare. AWT reports travel expanse coverage to attend scientific meetings and payment for lectures from Fisher and Paykel Healthcare, Covidien, Maquet-Getinge, Dräger Medical, General Electric Healthcare., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Despite scarce data, invasive mechanical ventilation (MV) is widely suggested as first-line ventilatory support in cardiogenic shock (CS) patients. We assessed the real-life use of different ventilation strategies in CS and their influence on short and mid-term prognosis., Methods: FRENSHOCK was a prospective registry including 772 CS patients from 49 centers in France. Patients were categorized into three groups according to the ventilatory supports during hospitalization: no mechanical ventilation group (NV), non-invasive ventilation alone group (NIV), and invasive mechanical ventilation group (MV). We compared clinical characteristics, management, and occurrence of death and major adverse event (MAE) (death, heart transplantation or ventricular assist device) at 30 days and 1 year between the three groups., Results: Seven hundred sixty-eight patients were included in this analysis. Mean age was 66 years and 71% were men. Among them, 359 did not receive any ventilatory support (46.7%), 118 only NIV (15.4%), and 291 MV (37.9%). MV patients presented more severe CS with more skin mottling, higher lactate levels, and higher use of vasoactive drugs and mechanical circulatory support. MV was associated with higher mortality and MAE at 30 days (HR 1.41 [1.05-1.90] and 1.52 [1.16-1.99] vs NV). No difference in mortality (HR 0.79 [0.49-1.26]) or MAE (HR 0.83 [0.54-1.27]) was found between NIV patients and NV patients. Similar results were found at 1-year follow-up., Conclusions: Our study suggests that using NIV is safe in selected patients with less profound CS and no other MV indication. NCT02703038., (© 2024. The Author(s).)

Background: Cardiogenic shock and sepsis are severe haemodynamic states that are frequently present concomitantly, leading to substantial mortality. Despite its frequency and clinical significance, there is a striking lack of literature on the outcomes of combined sepsis and cardiogenic shock., Methods: FRENSHOCK was a prospective registry including 772 patients with cardiogenic shock from 49 centres. The primary endpoint was 1-month all-cause mortality. Secondary endpoints included heart transplantation, ventricular assistance device and all-cause death rate at 1year., Results: Among the 772 patients with cardiogenic shock included, 92 cases were triggered by sepsis (11.9%), displaying more frequent renal and hepatic acute injuries, with lower mean arterial pressure. Patients in the sepsis group required broader use of dobutamine (90.1% vs. 81.2%; P=0.16), norepinephrine (72.5% vs. 50.8%; P<0.01), renal replacement therapy (29.7% vs. 14%; P<0.01), non-invasive ventilation (36.3% vs. 24.4%; P=0.09) and invasive ventilation (52.7% vs. 35.9%; P=0.02). Sepsis-triggered cardiogenic shock resulted in higher 1-month (41.3% vs. 24.0%; adjusted hazard ratio: 1.94, 95% confidence interval: 1.36-2.76; P<0.01) and 1-year (62.0% vs. 42.9%; adjusted hazard ratio 1.75, 95% confidence interval 1.32-2.33; P<0.01) all-cause death rates. No significant difference was found at 1year for heart transplantation or ventricular assistance device (8.7% vs. 10.3%; adjusted odds ratio 0.72, 95% confidence interval 0.32-1.64; P=0.43). In patients with sepsis-triggered cardiogenic shock, neither the presence of a preexisting cardiomyopathy nor the co-occurrence of other cardiogenic shock triggers had any additional impact on death., Conclusions: The association between sepsis and cardiogenic shock represents a common high-risk scenario, leading to higher short- and long-term death rates, regardless of the association with other cardiogenic shock triggers or the presence of preexisting cardiomyopathy., (Copyright © 2024. Published by Elsevier Masson SAS.)

To create robust and adaptable methods for lung pneumonia diagnosis and the assessment of its severity using chest X-rays (CXR), access to well-curated, extensive datasets is crucial. Many current severity quantification approaches require resource-intensive training for optimal results. Healthcare practitioners require efficient computational tools to swiftly identify COVID-19 cases and predict the severity of the condition. In this research, we introduce a novel image augmentation scheme as well as a neural network model founded on Vision Transformers (ViT) with a small number of trainable parameters for quantifying COVID-19 severity and other lung diseases. Our method, named Vision Transformer Regressor Infection Prediction (ViTReg-IP), leverages a ViT architecture and a regression head. To assess the model's adaptability, we evaluate its performance on diverse chest radiograph datasets from various open sources. We conduct a comparative analysis against several competing deep learning methods. Our results achieved a minimum Mean Absolute Error (MAE) of 0.569 and 0.512 and a maximum Pearson Correlation Coefficient (PC) of 0.923 and 0.855 for the geographic extent score and the lung opacity score, respectively, when the CXRs from the RALO dataset were used in training. The experimental results reveal that our model delivers exceptional performance in severity quantification while maintaining robust generalizability, all with relatively modest computational requirements. The source codes used in our work are publicly available at https://github.com/bouthainas/ViTReg-IP ., (© 2024. The Author(s).)

Importance: Ventilator-associated pneumonia (VAP) frequently occurs in patients with cardiac arrest. Diagnosis of VAP after cardiac arrest remains challenging, while the use of current biomarkers such as C-reactive protein (CRP) or procalcitonin (PCT) is debated., Objectives: To evaluate biomarkers' impact in helping VAP diagnosis after cardiac arrest., Design Setting and Participants: This is a prospective ancillary study of the randomized, multicenter, double-blind placebo-controlled ANtibiotherapy during Therapeutic HypothermiA to pRevenT Infectious Complications (ANTHARTIC) trial evaluating the impact of antibiotic prophylaxis to prevent VAP in out-of-hospital patients with cardiac arrest secondary to shockable rhythm and treated with therapeutic hypothermia. An adjudication committee blindly evaluated VAP according to predefined clinical, radiologic, and microbiological criteria. All patients with available biomarker(s), sample(s), and consent approval were included., Main Outcomes and Measures: The main endpoint was to evaluate the ability of biomarkers to correctly diagnose and predict VAP within 48 hours after sampling. The secondary endpoint was to study the combination of two biomarkers in discriminating VAP. Blood samples were collected at baseline on day 3. Routine and exploratory panel of inflammatory biomarkers measurements were blindly performed. Analyses were adjusted on the randomization group., Results: Among 161 patients of the ANTHARTIC trial with available biological sample(s), patients with VAP ( n = 33) had higher body mass index and Acute Physiology and Chronic Health Evaluation II score, more unwitnessed cardiac arrest, more catecholamines, and experienced more prolonged therapeutic hypothermia duration than patients without VAP ( n = 121). In univariate analyses, biomarkers significantly associated with VAP and showing an area under the curve (AUC) greater than 0.70 were CRP (AUC = 0.76), interleukin (IL) 17A and 17C (IL17C) (0.74), macrophage colony-stimulating factor 1 (0.73), PCT (0.72), and vascular endothelial growth factor A (VEGF-A) (0.71). Multivariate analysis combining novel biomarkers revealed several pairs with p value of less than 0.001 and odds ratio greater than 1: VEGF-A + IL12 subunit beta (IL12B), Fms-related tyrosine kinase 3 ligands (Flt3L) + C-C chemokine 20 (CCL20), Flt3L + IL17A, Flt3L + IL6, STAM-binding protein (STAMBP) + CCL20, STAMBP + IL6, CCL20 + 4EBP1, CCL20 + caspase-8 (CASP8), IL6 + 4EBP1, and IL6 + CASP8. Best AUCs were observed for CRP + IL6 (0.79), CRP + CCL20 (0.78), CRP + IL17A, and CRP + IL17C., Conclusions and Relevance: Our exploratory study shows that specific biomarkers, especially CRP combined with IL6, could help to better diagnose or predict early VAP occurrence in cardiac arrest patients., Competing Interests: The authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2024 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine.)

Background: Extracorporeal membrane oxygenation (ECMO) is associated with a high risk of bleeding complications. The specific impact of ECMO on fibrinolysis remains unexplored. The objective of the current pilot observational prospective study was to investigate the longitudinal dynamics of fibrinolytic markers-i.e., changes over time-in the context of bleeding events in patients on ECMO., Methods: Longitudinal dynamics of contact phase components (kininogen and bradykinin) and fibrinolysis markers (tissue plasminogen activator [tPA], plasminogen activator inhibitor-1 [PAI-1], their complexes [tPA•PAI-1], plasmin-antiplasmin complexes, plasminogen, and D-dimer) were measured in patients undergoing venovenous and venoarterial ECMO, before implantation, at 0, 6, and 12 h after implantation, and daily thereafter., Results: The cohort consisted of 30 patients (214 ECMO days). The concentrations of tPA, D-dimer, plasmin-antiplasmin complexes, PAI-1, and tPA•PAI-1 complexes were increased, whereas plasminogen decreased compared to normal values. A noteworthy divergence was observed between hemorrhagic and nonhemorrhagic patients: in bleeding patients, D-dimer, plasmin-antiplasmin, tPA, PAI-1, and tPA•PAI-1 followed an increasing kinetics before hemorrhage and then decreased to their baseline level; conversely, nonbleeding patients showed a decreasing kinetics in these markers. Also, D-dimer and tPA followed an increasing kinetics in bleeding patients compared to nonbleeding patients (median values for D-dimer dynamics: 1,080 vs. -440 ng/ml, P = 0.05; tPA dynamics: 0.130 vs. 0.100 nM, P = 0.038), and both markers significantly increased the day before hemorrhage. A tPA concentration above 0.304 nM was associated with bleeding events (odds ratio, 4.92; 95% CI, 1.01 to 24.08; P = 0.049)., Conclusions: Contact activation induces fibrinolysis in ECMO patients, especially in patients experiencing bleeding. This finding supports the role of this mechanism as a possible causal factor for hemorrhages during ECMO and open new avenues for novel therapeutic perspectives., (Copyright © 2024 American Society of Anesthesiologists. All Rights Reserved.)

Background: The Sequential Organ Failure Assessment (SOFA) score is an important tool in diagnosing sepsis and quantifying organ dysfunction. However, despite emerging evidence of differences in sepsis pathophysiology between women and men, sex is currently not being considered in the SOFA score. We aimed to investigate potential sex-specific differences in organ dysfunction, as measured by the SOFA score, in patients with sepsis or septic shock and explore outcome associations., Methods: Retrospective analysis of sex-specific differences in the SOFA score of prospectively enrolled ICU patients with sepsis or septic shock admitted to one of 85 certified Swiss ICUs between 01/2021 and 12/2022., Results: Of 125,782 patients, 5947 (5%) were admitted with a clinical diagnosis of sepsis (2244, 38%) or septic shock (3703, 62%). Of these, 5078 (37% women) were eligible for analysis. A statistically significant difference of the total SOFA score on admission was found between women (mean 7.5 ± SD 3.6 points) and men (7.8 ± 3.6 points, Wilcoxon rank-sum p < 0.001). This was driven by differences in the coagulation (p = 0.008), liver (p < 0.001) and renal (p < 0.001) SOFA components. Differences between sexes were more prominent in younger patients < 52 years of age (women 7.1 ± 4.0 points vs men 8.1 ± 4.2 points, p = 0.004). No sex-specific differences were found in ICU length of stay (women median 2.6 days (IQR 1.3-5.3) vs men 2.7 days (IQR 1.2-6.0), p = 0.13) and ICU mortality (women 14% vs men 15%, p = 0.17)., Conclusion: Sex-specific differences exist in the SOFA score of patients admitted to a Swiss ICU with sepsis or septic shock, particularly in laboratory-based components. Although the clinical meaningfulness of these differences is unclear, a reevaluation of sex-specific thresholds for SOFA score components is warranted in an attempt to make more accurate and individualised classifications., (© 2024. The Author(s).)

Background: Chronic kidney disease (CKD) is one of the leading causes of death worldwide, closely interrelated with cardiovascular diseases, ultimately leading to the failure of both organs - the so-called "cardiorenal syndrome". Despite this burden, data related to cardiogenic shock outcomes in CKD patients are scarce., Methods: FRENSHOCK (NCT02703038) was a prospective registry involving 772 patients with cardiogenic shock from 49 centres. One-year outcomes (rehospitalization, death, heart transplantation, ventricular assist device) were analysed according to history of CKD at admission and were adjusted on independent predictive factors., Results: CKD was present in 164 of 771 patients (21.3%) with cardiogenic shock; these patients were older (72.7 vs. 63.9years) and had more comorbidities than those without CKD. CKD was associated with a higher rate of all-cause mortality at 1month (36.6% vs. 23.2%; hazard ratio 1.39, 95% confidence interval 1.01-1.9; P=0.04) and 1year (62.8% vs. 40.5%, hazard ratio 1.39, 95% confidence interval 1.09-1.77; P<0.01). Patients with CKD were less likely to be treated with norepinephrine/epinephrine or undergo invasive ventilation or receive mechanical circulatory support, but were more likely to receive renal replacement therapy (RRT). RRT was associated with a higher risk of all-cause death at 1month and 1year regardless of baseline CKD status., Conclusions: Cardiogenic shock and CKD are frequent "cross-talking" conditions with limited therapeutic options, resulting in higher rates of death at 1month and 1year. RRT is a strong predictor of death, regardless of preexisting CKD. Multidisciplinary teams involving cardiac and kidney physicians are required to provide integrated care for patients with failure of both organs., (Copyright © 2024 The Author(s). Published by Elsevier Masson SAS.. All rights reserved.)

Background: The effects of pharmacological therapy on cardiogenic shock (CS) survivors have not been extensively studied. Thus, this study investigated the association between guideline-directed heart failure (HF) medical therapy (GDMT) and one-year survival rate in patients who are post-CS., Methods and Results: FRENSHOCK (French Observatory on the Management of Cardiogenic Shock in 2016) registry was a prospective multicenter observational survey, conducted in metropolitan French intensive care units and intensive cardiac care units. Of 772 patients, 535 patients were enrolled in the present analysis following the exclusion of 217 in-hospital deaths and 20 patients with missing medical records. Patients with triple GDMT (beta-blockers, renin-angiotensin system inhibitors, and mineralocorticoid receptor antagonists) at discharge (n=112) were likely to have lower left ventricular ejection fraction on admission and at discharge compared with those without triple GDMT (n=423) (22% versus 28%, P <0.001 and 29% versus 37%, P <0.001, respectively). In the overall cohort, the one-year mortality rate was 23%. Triple GDMT prescription was significantly associated with a lower one-year all-cause mortality compared with non-triple GDMT (adjusted hazard ratio 0.44 [95% CI, 0.19-0.80]; P =0.007). Similarly, 2:1 propensity score matching and inverse probability treatment weighting based on the propensity score demonstrated a lower incidence of one-year mortality in the triple GDMT group. As the number of HF drugs increased, a stepwise decrease in mortality was observed (log rank; P <0.001)., Conclusions: In survivors of CS, the one-year mortality rate was significantly lower in those with triple GDMT. Therefore, this study suggests that intensive HF therapy should be considered in patients following CS.

Importance: International guidelines recommend body temperature control below 37.8 °C in unconscious patients with out-of-hospital cardiac arrest (OHCA); however, a target temperature of 33 °C might lead to better outcomes when the initial rhythm is nonshockable., Objective: To assess whether hypothermia at 33 °C increases survival and improves function when compared with controlled normothermia in unconscious adults resuscitated from OHCA with initial nonshockable rhythm., Data Sources: Individual patient data meta-analysis of 2 multicenter, randomized clinical trials (Targeted Normothermia after Out-of-Hospital Cardiac Arrest [TTM2; NCT02908308] and HYPERION [NCT01994772]) with blinded outcome assessors. Unconscious patients with OHCA and an initial nonshockable rhythm were eligible for the final analysis., Study Selection: The study cohorts had similar inclusion and exclusion criteria. Patients were randomized to hypothermia (target temperature 33 °C) or normothermia (target temperature 36.5 to 37.7 °C), according to different study protocols, for at least 24 hours. Additional analyses of mortality and unfavorable functional outcome were performed according to age, sex, initial rhythm, presence or absence of shock on admission, time to return of spontaneous circulation, lactate levels on admission, and the cardiac arrest hospital prognosis score., Data Extraction and Synthesis: Only patients who experienced OHCA and had a nonshockable rhythm with all causes of cardiac arrest were included. Variables from the 2 studies were available from the original data sets and pooled into a unique database and analyzed. Clinical outcomes were harmonized into a single file, which was checked for accuracy of numbers, distributions, and categories. The last day of follow-up from arrest was recorded for each patient. Adjustment for primary outcome and functional outcome was performed using age, gender, time to return of spontaneous circulation, and bystander cardiopulmonary resuscitation., Main Outcomes and Measures: The primary outcome was mortality at 3 months; secondary outcomes included unfavorable functional outcome at 3 to 6 months, defined as a Cerebral Performance Category score of 3 to 5., Results: A total of 912 patients were included, 490 from the TTM2 trial and 422 from the HYPERION trial. Of those, 442 had been assigned to hypothermia (48.4%; mean age, 65.5 years; 287 males [64.9%]) and 470 to normothermia (51.6%; mean age, 65.6 years; 327 males [69.6%]); 571 patients had a first monitored rhythm of asystole (62.6%) and 503 a presumed noncardiac cause of arrest (55.2%). At 3 months, 354 of 442 patients in the hypothermia group (80.1%) and 386 of 470 patients in the normothermia group (82.1%) had died (relative risk [RR] with hypothermia, 1.04; 95% CI, 0.89-1.20; P = .63). On the last day of follow-up, 386 of 429 in the hypothermia group (90.0%) and 413 of 463 in the normothermia group (89.2%) had an unfavorable functional outcome (RR with hypothermia, 0.99; 95% CI, 0.87-1.15; P = .97). The association of hypothermia with death and functional outcome was consistent across the prespecified subgroups., Conclusions and Relevance: In this individual patient data meta-analysis, including unconscious survivors from OHCA with an initial nonshockable rhythm, hypothermia at 33 °C did not significantly improve survival or functional outcome.

Background: Disseminated intravascular coagulation (DIC) worsens the prognosis of septic shock and contributes to multiple organ failure. To date, no data linking DIC and acute kidney injury (AKI) occurrence, severity, and evolution in this setting are available. We aimed at analyzing the association between AKI occurrence, severity and evolution in patients with septic shock-induced DIC. In a prospective monocentric cohort study, consecutive patients, 18 years and older, admitted in the ICU of Strasbourg University Hospital in the setting of systemic hypotension requiring vasopressor related to an infection, without history of terminal chronic kidney disease were eligible. AKI was defined according to the KDIGO classification. DIC diagnosis was based on the International Society on Thrombosis and Haemostasis (ISTH) score. Evolution of AKI was evaluated through the composite endpoint of major adverse kidney events. Only patients with DIC that occurred before or at the time of AKI diagnosis were considered. Univariate and multivariate analysis were performed to determine factors associated with renal outcomes., Results: 350 patients were included, of whom 129 experienced DIC. Patients with DIC were more seriously ill (median SAPS II 64 vs. 56, p < 0.001), and had higher 28-day mortality (43.3% vs. 26.2%, p < 0.001). AKI was more frequent in patients with DIC (86.8% vs. 74.2%, p < 0.005), particularly for the more severe stage of AKI [KDIGO 3 in 58.1% of patients with DIC vs. 30.8% of patients without DIC, p < 0.001, AKI requiring renal replacement therapy (RRT) in 47.3% of patients with DIC vs. 21.3% of patients without DIC, p < 0.001]. After adjustment for confounding factors, DIC occurrence remained associated with the risk of having the more severe stage of AKI with an odds ratio (OR) of 2.74 [IC 95% (1.53-4.91), p < 0.001], and with the risk of requiring RRT during the ICU stay [OR 2.82 (1.53-5.2), p < 0.001]., Conclusion: DIC appears to be strongly associated with the risk of developing the more severe form of AKI (stage 3 of the KDIGO classification, RRT requirement), even after adjustment for severity and other relevant factors., (© 2023. The Author(s).)

Background: Whether preventive inhaled antibiotics may reduce the incidence of ventilator-associated pneumonia is unclear., Methods: In this investigator-initiated, multicenter, double-blind, randomized, controlled, superiority trial, we assigned critically ill adults who had been undergoing invasive mechanical ventilation for at least 72 hours to receive inhaled amikacin at a dose of 20 mg per kilogram of ideal body weight once daily or to receive placebo for 3 days. The primary outcome was a first episode of ventilator-associated pneumonia during 28 days of follow-up. Safety was assessed., Results: A total of 850 patients underwent randomization, and 847 were included in the analyses (417 assigned to the amikacin group and 430 to the placebo group). All three daily nebulizations were received by 337 patients (81%) in the amikacin group and 355 patients (83%) in the placebo group. At 28 days, ventilator-associated pneumonia had developed in 62 patients (15%) in the amikacin group and in 95 patients (22%) in the placebo group (difference in restricted mean survival time to ventilator-associated pneumonia, 1.5 days; 95% confidence interval [CI], 0.6 to 2.5; P = 0.004). An infection-related ventilator-associated complication occurred in 74 patients (18%) in the amikacin group and in 111 patients (26%) in the placebo group (hazard ratio, 0.66; 95% CI, 0.50 to 0.89). Trial-related serious adverse effects were seen in 7 patients (1.7%) in the amikacin group and in 4 patients (0.9%) in the placebo group., Conclusions: Among patients who had undergone mechanical ventilation for at least 3 days, a subsequent 3-day course of inhaled amikacin reduced the burden of ventilator-associated pneumonia during 28 days of follow-up. (Funded by the French Ministry of Health; AMIKINHAL ClinicalTrials.gov number, NCT03149640; EUDRA Clinical Trials number, 2016-001054-17.)., (Copyright © 2023 Massachusetts Medical Society.)

Aims: Characteristics, management, and outcomes of patients with active cancer admitted for cardiogenic shock remain largely unknown. This study aimed to address this issue and identify the determinants of 30-day and 1-year mortality in a large cardiogenic shock cohort of all aetiologies., Methods and Results: FRENSHOCK is a prospective multicenter observational registry conducted in French critical care units between April and October 2016. 'Active cancer' was defined as a malignancy diagnosed within the previous weeks with planned or ongoing anticancer therapy. Among the 772 enrolled patients (mean age 65.7 ± 14.9 years; 71.5% male), 51 (6.6%) had active cancer. Among them, the main cancer types were solid cancers (60.8%), and hematological malignancies (27.5%). Solid cancers were mainly urogenital (21.6%), gastrointestinal (15.7%), and lung cancer (9.8%). Medical history, clinical presentation, and baseline echocardiography were almost the same between groups. In-hospital management significantly differed: patients with cancers received more catecholamines or inotropes (norepinephrine 72% vs. 52%, P = 0.005 and norepinephrine-dobutamine combination 64.7% vs. 44.5%, P = 0.005), but had less mechanical circulatory support (5.9% vs. 19.5%, P = 0.016). They presented a similar 30-day mortality rate (29% vs. 26%) but a significantly higher mortality at 1-year (70.6% vs. 45.2%, P < 0.001). In multivariable analysis, active cancer was not associated with 30-day mortality but was significantly associated with 1-year mortality in 30-day survivors [HR 3.61 (1.29-10.11), P = 0.015]., Conclusion: Active cancer patients accounted for almost 7% of all cases of cardiogenic shock. Early mortality was the same regardless of active cancer or not, whereas long-term mortality was significantly increased in patients with active cancer., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Despite significant advancements in critical care medicine, limited attention has been given to sex and gender disparities in management and outcomes of patients admitted to the intensive care unit (ICU). While "sex" pertains to biological and physiological characteristics, such as reproductive organs, chromosomes and sex hormones, "gender" refers more to sociocultural roles and human behavior. Unfortunately, data on gender-related topics in the ICU are lacking. Consequently, data on sex and gender-related differences in admission to the ICU, clinical course, length of stay, mortality, and post-ICU burdens, are often inconsistent. Moreover, when examining specific diagnoses in the ICU, variations can be observed in epidemiology, pathophysiology, presentation, severity, and treatment response due to the distinct impact of sex hormones on the immune and cardiovascular systems. In this narrative review, we highlight the influence of sex and gender on the clinical course, management, and outcomes of the most encountered intensive care conditions, in addition to the potential co-existence of unconscious biases which may also impact critical illness. Diagnoses with a known sex predilection will be discussed within the context of underlying sex differences in physiology, anatomy, and pharmacology with the goal of identifying areas where clinical improvement is needed. To optimize patient care and outcomes, it is crucial to comprehend and address sex and gender differences in the ICU setting and personalize management accordingly to ensure equitable, patient-centered care. Future research should focus on elucidating the underlying mechanisms driving sex and gender disparities, as well as exploring targeted interventions to mitigate these disparities and improve outcomes for all critically ill patients., (© 2023. The Author(s).)

Objectives: Staphylococcus epidermidis (SE) is a supposedly low-virulence agent, which may cause proven bloodstream infections (BSIs), with little-known consequences on intensive care unit (ICU) patients. We aimed at studying ICU patients diagnosed with BSIs caused by SE (SE-BSIs)., Methods: We constituted a retrospective cohort in two medical ICUs. SE-BSIs were defined by two or more independent SE-positive blood cultures of the same strain, within 48 hours, without concurrent infection., Results: We included 59 patients; 58% were men (n = 34), with median age of 67 (interquartile range 60-74) years and a simplified acute physiology score II of 59 (36-74) points, and 56% were immunocompromised (n = 33). Among the 37 (63%) patients requiring norepinephrine initiation or increase at the onset of SE-BSI versus patients not requiring vasopressors (37%; n = 22), concomitant arterial lactate levels reached 2.8 (1.9-5.8) versus 1.5 (1.3-2.2) mmol/l (P <0.01), whereas the mean blood pressure was 49 (42-54) versus 61 (56-65) mm Hg (P = 0.01) and the mortality was 46% (n = 17) vs 14% (n = 3) at day 28 (P = 0.01), respectively. Regarding antibiotics, the susceptibility rates toward linezolid and vancomycin were 71% (n = 41/58) and 100% (n = 54/54), respectively. At the time of SE-BSI, all but one patient had a central venous access device., Conclusion: This work highlights SE-BSIs as a cause of septic shock, mostly in immunocompromised ICU patients, with increasing concerns about resistance to antibiotics and central line management., Competing Interests: Declarations of competing interest The authors have no competing interests to declare., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background & Aims: After a prolonged intensive care unit (ICU) stay patients experience increased mortality and morbidity. The primary aim of this study was to assess the prognostic value of nutritional status, body mass composition and muscle strength, as assessed by body mass index (BMI), bioelectrical impedance analysis (BIA), handgrip (HG) test, and that of the biological features to predict one-year survival at the end of a prolonged ICU stay., Methods: This was a multicenter prospective observational study. Survivor patients older than 18 years with ICU length of stay >72 h were eligible for inclusion. BIA and HG were performed at the end of the ICU stay. Malnutrition was defined by BMI and fat-free mass index (FFMI). The primary endpoint was one-year mortality. Multivariable logistic regression was performed to determine parameters associated with mortality., Results: 572 patients were included with a median age of 63 years [53.5; 71.1], BMI of 26.6 kg/m 2 [22.8; 31.3], SAPS II score of 43 [31; 58], and ICU length of stay of 9 days [6; 15]. Malnutrition was observed in 142 (24.9%) patients. During the 1-year follow-up after discharge, 96 (18.5%) patients died. After adjustment, a low HG test score (aOR = 1.44 [1.11; 1.89], p = 0.01) was associated with 1-year mortality. Patients with low HG score, malnutrition, and Albuminemia <30 g/L had a one-year death rate of 41.4%. Conversely, patients with none of these parameters had a 1-year death rate of 4.1%., Conclusion: BIA to assess FFMI, HG and albuminemia at the end of ICU stay could be used to predict 1-year mortality. Their ability to identify patients eligible for a structured recovery program could be studied., Competing Interests: Conflicts of interest The authors declare that they have no conflict of interest., (Copyright © 2023. Published by Elsevier Ltd.)

Background: Cardiac arrest is the most life-threatening complication of attempted suicide by hanging. However, data are scarce on its characteristics and outcome predictors., Methods: This retrospective observational multicentre study in 31 hospitals included consecutive adults admitted after cardiac arrest induced by suicidal hanging. Factors associated with in-hospital mortality were identified by multivariate logistic regression with multiple imputations for missing data and adjusted to the temporal trends over the study period., Results: Of 450 patients (350 men, median age, 43 [34-52] years), 305 (68%) had a psychiatric history, and 31 (6.9%) attempted hanging while hospitalized. The median time from unhanging to cardiopulmonary resuscitation was 0 [0-5] min, and the median time to return of spontaneous circulation (ROSC) was 20 [10-30] min. Seventy-nine (18%) patients survived to hospital discharge. Three variables were independently associated with higher in-hospital mortality: time from collapse or unhanging to ROSC>20 min (odds ratio [OR], 4.71; 95% confidence intervals [95%CIs], 2.02-10.96; p = 0.0004); glycaemia >1.4 g/L at admission (OR, 6.38; 95%CI, 2.60-15.66; p < 0.0001); and lactate >3.5 mmol/L at admission (OR, 6.08; 95%CI, 1.71-21.06; p = 0.005). A Glasgow Coma Scale (GCS) score of >5 at admission was associated with lower in-hospital mortality (OR, 0.009; 95%CI, 0.02-0.37; p = 0.0009)., Conclusion: In patients with hanging-induced cardiac arrest, time from collapse or unhanging to return of spontaneous circulation, glycaemia, arterial lactate, and coma depth at admission were independently associated with survival to hospital discharge. Knowledge of these risk factors may help guide treatment decisions in these patients at high risk of hospital mortality., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Salvetti, Schnell, Pichon, Schenck, Cronier, Perbet, Lascarrou, Guitton, Lesieur, Argaud, Colin, Cholley, Quenot, Merdji, Geeraerts, Piagnerelli, Jacq, Paul, Chelly, de Charentenay, Deye, Danguy des Déserts, Thiery, Simon, Das, Jacobs, Cerf, Mayaux, Beuret, Ouchenir, Lafarge, Sauneuf, Daubin, Cariou, Silva and Legriel.)

Aims: Impact of skin mottling has been poorly studied in patients admitted for cardiogenic shock. This study aimed to address this issue and identify determinants of 30-day and 1-year mortality in a large cardiogenic shock cohort of all etiologies., Methods and Results: FRENSHOCK is a prospective multicenter observational registry conducted in French critical care units between April and October, 2016. Among the 772 enrolled patients (mean age 65.7 ± 14.9 years; 71.5% male), 660 had skin mottling assessed at admission (85.5%) with almost 39% of patients in cardiogenic shock presenting mottling. The need for invasive respiratory support was significantly higher in patients with mottling (50.2% vs. 30.1%, p < 0.001) and likewise for the need for renal replacement therapy (19.9% vs. 12.4%, p = 0.09). However, the need for mechanical circulatory support was similar in both groups. Patients with mottling at admission presented a higher length of stay (19 vs. 16 days, p = 0.033), a higher 30-day mortality rate (31% vs. 23.3%, p = 0.031), and also showed significantly higher mortality at 1-year (54% vs. 42%, p = 0.003). The subgroup of patients in whom mottling appeared during the first 24 h after admission had the worst prognosis at 30 days., Conclusion: Skin mottling at admission in patients with cardiogenic shock was statistically associated with prolonged length of stay and poor outcomes. As a perfusion-targeted resuscitation parameter, mottling is a simple, clinical-based approach and may thus help to improve and guide immediate goal-directed therapy to improve cardiogenic shock patients' outcomes., (© 2023. La Société de Réanimation de Langue Francaise = The French Society of Intensive Care (SRLF).)

Background: Respiratory mechanics is a key element to monitor mechanically ventilated patients and guide ventilator settings. Besides the usual basic assessments, some more complex explorations may allow to better characterize patients' respiratory mechanics and individualize ventilation strategies. These advanced respiratory mechanics assessments including esophageal pressure measurements and complete airway closure detection may be particularly relevant in critically ill obese patients. This study aimed to comprehensively assess respiratory mechanics in obese and non-obese ICU patients with or without ARDS and evaluate the contribution of advanced respiratory mechanics assessments compared to basic assessments in these patients., Methods: All intubated patients admitted in two ICUs for any cause were prospectively included. Gas exchange and respiratory mechanics including esophageal pressure and end-expiratory lung volume (EELV) measurements and low-flow insufflation to detect complete airway closure were assessed in standardized conditions (tidal volume of 6 mL kg -1 predicted body weight (PBW), positive end-expiratory pressure (PEEP) of 5 cmH 2 O) within 24 h after intubation., Results: Among the 149 analyzed patients, 52 (34.9%) were obese and 90 (60.4%) had ARDS (65.4% and 57.8% of obese and non-obese patients, respectively, p = 0.385). A complete airway closure was found in 23.5% of the patients. It was more frequent in obese than in non-obese patients (40.4% vs 14.4%, p < 0.001) and in ARDS than in non-ARDS patients (30% vs. 13.6%, p = 0.029). Respiratory system and lung compliances and EELV/PBW were similarly decreased in obese patients without ARDS and obese or non-obese patients with ARDS. Chest wall compliance was not impacted by obesity or ARDS, but end-expiratory esophageal pressure was higher in obese than in non-obese patients. Chest wall contribution to respiratory system compliance differed widely between patients but was not predictable by their general characteristics., Conclusions: Most respiratory mechanics features are similar in obese non-ARDS and non-obese ARDS patients, but end-expiratory esophageal pressure is higher in obese patients. A complete airway closure can be found in around 25% of critically ill patients ventilated with a PEEP of 5 cmH 2 O. Advanced explorations may allow to better characterize individual respiratory mechanics and adjust ventilation strategies in some patients. Trial registration NCT03420417 ClinicalTrials.gov (February 5, 2018)., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Competing Interests: Conflict of interest: None declared.

Competing Interests: Conflict of interest: All of the authors declare to have no conflict of interest.

Cardiogenic shock is usually defined as primary cardiac dysfunction with low cardiac output leading to critical organ hypoperfusion, and tissue hypoxia, resulting in high mortality rate between 40% and 50% despite recent advances. Many studies have now evidenced that cardiogenic shock not only involves systemic macrocirculation, such as blood pressure, left ventricular ejection fraction, or cardiac output, but also involves significant systemic microcirculatory abnormalities which seem strongly associated with the outcome. Although microcirculation has been widely studied in the context of septic shock showing heterogeneous alterations with clear evidence of macro and microcirculation uncoupling, there is now a growing body of literature focusing on cardiogenic shock states. Even if there is currently no consensus regarding the treatment of microcirculatory disturbances in cardiogenic shock, some treatments seem to show a benefit. Furthermore, a better understanding of the underlying pathophysiology may provide hypotheses for future studies aiming to improve cardiogenic shock prognosis., (© 2023. The Author(s).)

Biological rhythms are important regulators of immune functions. In intensive care unit (ICU), sepsis is known to be associated with rhythm disruption. Our objectives were to determine factors associated with rhythm disruption of the body temperature and to assess the relationship between temperature and mortality in septic shock patients; In a cohort of septic shock, we recorded body temperature over a 24-h period on day 2 after ICU admission. For each patient, the temperature rhythmicity was assessed by defining period and amplitude, and the adjusted average (mesor) of the temperature by sinusoidal regression and cosinor analysis. Analyses were performed to assess factors associated with the three temperature parameters (period, amplitude, and mesor) and mortality. 162 septic shocks were enrolled. The multivariate analysis demonstrates that the period of temperature was associated with gender (women, coefficient -2.2 h, p = 0.031) and acetaminophen use (coefficient -4.3 h, p = 0.002). The mesor was associated with SOFA score (coefficient -0.05 °C per SOFA point, p = 0.046), procalcitonin (coefficient 0.001 °C per ng/mL, p = 0.005), and hydrocortisone use (coefficient -0.5 °C, p = 0.002). The amplitude was associated with the dialysis (coefficient -0.5 °C, p = 0.002). Mortality at day 28 was associated with lower mesor (adjusted hazard ratio 0.50, 95% CI 0.28 to 0.90; p = 0.02), and higher amplitude (adjusted hazard ratio 5.48, 95% CI 1.66 to 18.12; p = 0.005) of temperature. Many factors, such as therapeutics, influence the body temperature during septic shock. Lower mesor and higher amplitude were associated with mortality and could be considered prognostic markers in ICU. In the age of artificial intelligence, the incorporation of such data in an automated scoring alert could compete with physicians to identify high-risk patients during septic shock.

Background: Timely management of acute myocardial infarction (AMI) and acute stroke has undergone impressive progress during the last decade. However, it is currently unknown whether both sexes have profited equally from improved strategies. We sought to analyze sex-specific temporal trends in intensive care unit (ICU) admission and mortality in younger patients presenting with AMI or stroke in Switzerland., Methods: Retrospective analysis of temporal trends in 16,954 younger patients aged 18 to ≤ 52 years with AMI or acute stroke admitted to Swiss ICUs between 01/2008 and 12/2019., Results: Over a period of 12 years, ICU admissions for AMI decreased more in women than in men (- 6.4% in women versus - 4.5% in men, p < 0.001), while ICU mortality for AMI significantly increased in women (OR 1.2 [1.10-1.30], p = 0.032), but remained unchanged in men (OR 0.99 [0.94-1.03], p = 0.71). In stroke patients, ICU admission rates increased between 3.6 and 4.1% per year in both sexes, while ICU mortality tended to decrease only in women (OR 0.91 [0.85-0.95, p = 0.057], but remained essentially unaltered in men (OR 0.99 [0.94-1.03], p = 0.75). Interventions aimed at restoring tissue perfusion were more often performed in men with AMI, while no sex difference was noted in neurovascular interventions., Conclusion: Sex and gender disparities in disease management and outcomes persist in the era of modern interventional neurology and cardiology with opposite trends observed in younger stroke and AMI patients admitted to intensive care. Although our study has several limitations, our data suggest that management and selection criteria for ICU admission, particularly in younger women with AMI, should be carefully reassessed., (© 2023. The Author(s).)

Background: Several studies have reported an increased risk of thrombotic events in COVID-19 patients, but the pathophysiology of this procoagulant phenotype remains poorly understood. We hypothesized that corticosteroids may attenuate this procoagulant state through their anti-inflammatory effects. The aim of this study was to evaluate the impact of dexamethasone (DXM) on the coagulation profile of severely ill COVID-19 patients., Methods: We conducted a retrospective, observational before/after bi-centric cohort study among ICU patients hospitalized for severe COVID-19 and receiving therapeutic anticoagulation by unfractionated heparin (UFH). Before and after the standardized use of DXM, we compared inflammatory and coagulation profiles, as well as the kinetics of heparin requirement, adjusted for weight and anti-Xa activity., Results: Eighty-six patients were included, 35 in the no-DXM group, and 51 in the DXM group. At admission, CRP and fibrinogen levels were not different between groups, neither were UFH infusion rates. At day 3 after ICU admission, CRP (178±94 mg/L vs. 99±68 mg/L, P<0.001) and fibrinogen (7.2±1.4 g/L vs. 6.1±1.4 g/L, P=0.001) significantly decreased in the DXM group, but not in the no-DXM group. Over time, UFH infusion rates were lower in the DXM group (P<0.001) without any significant difference in plasma anti-Xa activity. CRP variations correlated with heparin dose variations between Day 0 and Day 3 (r=0.39, P=0.009). Finally, the incidence of venous thromboembolic events during in-ICU stay was significantly reduced in the DXM group (4 vs. 43%, P<0.0001)., Conclusions: In critically ill COVID-19 patients, dexamethasone use was associated with a decrease in both pro-inflammatory and procoagulant profile.

Rationale: Identification of cardiogenic shock severity is a critical step to adapt the management level upon admission. Peripheral tissue perfusion signs, simple and reliable markers of tissue hypoperfusion have never been extensively assessed during cardiogenic shock. Objectives: To assess the correlation of capillary refill time values with 90-day mortality in cardiogenic shock patients or the need for venoarterial extracorporeal membrane oxygenation (VA-ECMO) support. Also to assess the correlation between capillary refill time and hemodynamic parameters. Methods: All consecutive patients with cardiogenic shock admitted to the intensive care unit of two tertiary teaching hospitals were included in a prospective observational study. Macro-hemodynamic parameters (such as heart rate, blood pressure, left ventricular ejection fraction, and cardiac index) and peripheral tissue perfusion signs, such as capillary refill time on the index fingertip, mottling, and Pv-aCO 2 (the difference between partial pressure of CO 2 between venous and arterial blood) were recorded at inclusion (0 hour), 6 hours, 12 hours, 24 hours, and 48 hours. The composite primary endpoint was the association between 90-day mortality or the need for VA-ECMO support. Measurements and Main Results: A total of 61 patients were included; at inclusion, simplified acute physiology score II was 64 (52-77) points. The primary endpoint was met by 42% of patients. Capillary refill time values were significantly higher at all time points in nonsurvivors or patients needing VA-ECMO support. In univariate analysis, capillary refill time > 3 seconds at inclusion was associated with 90-day all-cause mortality or VA-ECMO support (hazard ratio, 12.38; 95% confidence interval, 2.91-52.71). Capillary refill time at inclusion was poorly associated with macrocirculatory parameters but significantly correlated with microcirculatory parameters. Further, capillary refill time added incremental value to Cardshock score, with an AUC combination at 0.93. Conclusions: In patients with cardiogenic shock admitted to the ICU, our preliminary data suggest that a prolonged capillary refill time >3 seconds was associated with an early prediction of 90-day mortality or the need for VA-ECMO support.

Background: Outcomes of postresuscitation shock after cardiac arrest can be affected by targeted temperature management (TTM). A post hoc analysis of the "TTM1 trial" suggested higher mortality with hypothermia at 33 °C. We performed a post hoc analysis of HYPERION trial data to assess potential associations linking postresuscitation shock after non-shockable cardiac arrest to hypothermia at 33 °C on favourable functional outcome., Methods: We divided the patients into groups with vs. without postresuscitation (defined as the need for vasoactive drugs) shock then assessed the proportion of patients with a favourable functional outcome (day-90 Cerebral Performance Category [CPC] 1 or 2) after hypothermia (33 °C) vs. controlled normothermia (37 °C) in each group. Patients with norepinephrine or epinephrine > 1 µg/kg/min were not included., Results: Of the 581 patients included in 25 ICUs in France and who did not withdraw consent, 339 had a postresuscitation shock and 242 did not. In the postresuscitation-shock group, 159 received hypothermia, including 14 with a day-90 CPC of 1-2, and 180 normothermia, including 10 with a day-90 CPC of 1-2 (8.81% vs. 5.56%, respectively; P = 0.24). After adjustment, the proportion of patients with CPC 1-2 also did not differ significantly between the hypothermia and normothermia groups (adjusted hazards ratio, 1.99; 95% confidence interval, 0.72-5.50; P = 0.18). Day-90 mortality was comparable in these two groups (83% vs. 86%, respectively; P = 0.43)., Conclusions: After non-shockable cardiac arrest, mild-to-moderate postresuscitation shock at intensive-care-unit admission did not seem associated with day-90 functional outcome or survival. Therapeutic hypothermia at 33 °C was not associated with worse outcomes compared to controlled normothermia in patients with postresuscitation shock. Trial registration ClinicalTrials.gov, NCT01994772., (© 2022. The Author(s).)

Importance: The benefit of high-flow nasal cannula oxygen (high-flow oxygen) in terms of intubation and mortality in patients with respiratory failure due to COVID-19 is controversial., Objective: To determine whether the use of high-flow oxygen, compared with standard oxygen, could reduce the rate of mortality at day 28 in patients with respiratory failure due to COVID-19 admitted in intensive care units (ICUs)., Design, Setting, and Participants: The SOHO-COVID randomized clinical trial was conducted in 34 ICUs in France and included 711 patients with respiratory failure due to COVID-19 and a ratio of partial pressure of arterial oxygen to fraction of inspired oxygen equal to or below 200 mm Hg. It was an ancillary trial of the ongoing original SOHO randomized clinical trial, which was designed to include patients with acute hypoxemic respiratory failure from all causes. Patients were enrolled from January to December 2021; final follow-up occurred on March 5, 2022., Interventions: Patients were randomly assigned to receive high-flow oxygen (n = 357) or standard oxygen delivered through a nonrebreathing mask initially set at a 10-L/min minimum (n = 354)., Main Outcomes and Measures: The primary outcome was mortality at day 28. There were 13 secondary outcomes, including the proportion of patients requiring intubation, number of ventilator-free days at day 28, mortality at day 90, mortality and length of stay in the ICU, and adverse events., Results: Among the 782 randomized patients, 711 patients with respiratory failure due to COVID-19 were included in the analysis (mean [SD] age, 61 [12] years; 214 women [30%]). The mortality rate at day 28 was 10% (36/357) with high-flow oxygen and 11% (40/354) with standard oxygen (absolute difference, -1.2% [95% CI, -5.8% to 3.4%]; P = .60). Of 13 prespecified secondary outcomes, 12 showed no significant difference including in length of stay and mortality in the ICU and in mortality up until day 90. The intubation rate was significantly lower with high-flow oxygen than with standard oxygen (45% [160/357] vs 53% [186/354]; absolute difference, -7.7% [95% CI, -14.9% to -0.4%]; P = .04). The number of ventilator-free days at day 28 was not significantly different between groups (median, 28 [IQR, 11-28] vs 23 [IQR, 10-28] days; absolute difference, 0.5 days [95% CI, -7.7 to 9.1]; P = .07). The most common adverse events were ventilator-associated pneumonia, occurring in 58% (93/160) in the high-flow oxygen group and 53% (99/186) in the standard oxygen group., Conclusions and Relevance: Among patients with respiratory failure due to COVID-19, high-flow nasal cannula oxygen, compared with standard oxygen therapy, did not significantly reduce 28-day mortality., Trial Registration: ClinicalTrials.gov Identifier: NCT04468126.

Importance: The benefit of high-dose dexamethasone and oxygenation strategies vs standard of care for patients with severe acute hypoxemic respiratory failure (AHRF) caused by COVID-19 pneumonia is debated., Objectives: To assess the benefit of high-dose dexamethasone compared with standard of care dexamethasone, and to assess the benefit of high-flow nasal oxygen (HFNo2) or continuous positive airway pressure (CPAP) compared with oxygen support standard of care (o2SC)., Design, Setting, and Participants: This multicenter, placebo-controlled randomized clinical trial was conducted in 19 intensive care units (ICUs) in France from April 2020 to January 2021. Eligible patients were consecutive ICU-admitted adults with COVID-19 AHRF. Randomization used a 2 × 3 factorial design for dexamethasone and oxygenation strategies; patients not eligible for at least 1 oxygenation strategy and/or already receiving invasive mechanical ventilation (IMV) were only randomized for dexamethasone. All patients were followed-up for 60 days. Data were analyzed from May 26 to July 31, 2021., Interventions: Patients received standard dexamethasone (dexamethasone-phosphate 6 mg/d for 10 days [or placebo prior to RECOVERY trial results communication]) or high-dose dexamethasone (dexamethasone-phosphate 20 mg/d on days 1-5 then 10 mg/d on days 6-10). Those not requiring IMV were additionally randomized to o2SC, CPAP, or HFNo2., Main Outcomes and Measures: The main outcomes were time to all-cause mortality, assessed at day 60, for the dexamethasone interventions, and time to IMV requirement, assessed at day 28, for the oxygenation interventions. Differences between intervention groups were calculated using proportional Cox models and expressed as hazard ratios (HRs)., Results: Among 841 screened patients, 546 patients (median [IQR] age, 67.4 [59.3-73.1] years; 414 [75.8%] men) were randomized between standard dexamethasone (276 patients, including 37 patients who received placebo) or high-dose dexamethasone (270 patients). Of these, 333 patients were randomized among o2SC (109 patients, including 56 receiving standard dexamethasone), CPAP (109 patients, including 57 receiving standard dexamethasone), and HFNo2 (115 patients, including 56 receiving standard dexamethasone). There was no difference in 60-day mortality between standard and high-dose dexamethasone groups (HR, 0.96 [95% CI, 0.69-1.33]; P = .79). There was no significant difference for the cumulative incidence of IMV criteria at day 28 among o2 support groups (o2SC vs CPAP: HR, 1.08 [95% CI, 0.71-1.63]; o2SC vs HFNo2: HR, 1.04 [95% CI, 0.69-1.55]) or 60-day mortality (o2SC vs CPAP: HR, 0.97 [95% CI, 0.58-1.61; o2SC vs HFNo2: HR, 0.89 [95% CI, 0.53-1.47]). Interactions between interventions were not significant., Conclusions and Relevance: In this randomized clinical trial among ICU patients with COVID-19-related AHRF, high-dose dexamethasone did not significantly improve 60-day survival. The oxygenation strategies in patients who were not initially receiving IMV did not significantly modify 28-day risk of IMV requirement., Trial Registration: ClinicalTrials.gov Identifier: NCT04344730; EudraCT: 2020-001457-43.

Sophisticated cancer treatments, cardiovascular risk factors, and aging trigger acute cardiovascular diseases in an increasing number of cancer patients. Among acute cardiovascular diseases, cancer treatment, as well as the cancer disease itself, may induce a cardiogenic shock. Although increasing, these cardiogenic shocks are still relatively limited, and their management is a matter of debate in cancer patients. Etiologies that cause cardiogenic shock are slightly different from those of non-cancer patients, and management has some specific features always requiring a multidisciplinary approach. Recent guidelines and extensive data from the scientific literature can provide useful guidance for the management of these critical patients. Even if no etiologic therapy is available, maximal intensive supportive measures can often be justified, as most of these cardiogenic shocks are potentially reversible. In this review, we address the major etiologies that can lead to cardiogenic shock in cancer patients and discuss issues related to its management., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Curtiaud, Delmas, Gantzer, Zafrani, Siegemund, Meziani and Merdji.)

Background: In patients with septic shock, the impact of the mean arterial pressure (MAP) target on the course of mottling remains uncertain. In this post hoc analysis of the SEPSISPAM trial, we investigated whether a low-MAP (65 to 70 mmHg) or a high-MAP target (80 to 85 mmHg) would affect the course of mottling and arterial lactate in patients with septic shock., Methods: The presence of mottling was assessed every 2 h from 2 h after inclusion to catecholamine weaning. We compared mottling and lactate time course between the two MAP target groups. We evaluated the patient's outcome according to the presence or absence of mottling., Results: We included 747 patients, 374 were assigned to the low-MAP group and 373 to the high-MAP group. There was no difference in mottling and lactate evolution during the first 24 h between the two MAP groups. After adjustment for MAP and confounding factors, the presence of mottling ≥ 6 h during the first 24 h was associated with a significantly higher risk of death at day 28 and 90. Patients without mottling or with mottling < 6 h and lactate ≥ 2 mmol/L have a higher probability of survival than those with mottling ≥ 6 h and lactate < 2 mmol/L., Conclusion: Compared with low MAP target, higher MAP target did not alter mottling and lactate course. Mottling lasting for more than 6 h was associated with higher mortality. Compared to arterial lactate, mottling duration appears to be a better marker of mortality., (© 2022. The Author(s).)

Background: Targeted temperature management (TTM) currently is the only treatment with demonstrated efficacy in attenuating the harmful effects on the brain of ischemia-reperfusion injury after cardiac arrest. However, whether TTM is beneficial in the subset of patients with in-hospital cardiac arrest (IHCA) remains unclear., Research Question: Is TTM at 33 °C associated with better neurological outcomes after IHCA in a nonshockable rhythm compared with targeted normothermia (TN; 37 °C)?, Study Design and Methods: We performed a post hoc analysis of data from the published Targeted Temperature Management for Cardiac Arrest with Nonshockable Rhythm randomized controlled trial in 584 patients. We included the 159 patients with IHCA; 73 were randomized to 33 °C treatment and 86 were randomized to 37 °C treatment. The primary outcome was survival with a good neurologic outcome (cerebral performance category [CPC] score of 1 or 2) on day 90. Mixed multivariate adjusted logistic regression analysis was performed to determine whether survival with CPC score of 1 or 2 on day 90 was associated with type of temperature management after adjustment on baseline characteristics not balanced by randomization., Results: Compared with TN for 48 h, hypothermia at 33 °C for 24 h was associated with a higher percentage of patients who were alive with good neurologic outcomes on day 90 (16.4% vs 5.8%; P = .03). Day 90 mortality was not significantly different between the two groups (68.5% vs 76.7%; P = .24). By mixed multivariate analysis adjusted by Cardiac Arrest Hospital Prognosis score and circulatory shock status, hypothermia was associated significantly with good day 90 neurologic outcomes (OR, 2.40 [95% CI, 1.17-13.03]; P = .03)., Interpretation: Hypothermia at 33 °C was associated with better day 90 neurologic outcomes after IHCA in a nonshockable rhythm compared with TN. However, the limited sample size resulted in wide CIs. Further studies of patients after cardiac arrest resulting from any cause, including IHCA, are needed., (Copyright © 2022 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Background: Patients admitted after cardiac arrest with non-shockable rhythm frequently experience hemodynamic instability. This study assessed the hemodynamic consequences of TTM in this sub population., Methods: This is a post hoc analysis of the HYPERION trial (NCT01994772), that randomized patients to either hypothermia or normothermia after non-shockable rhythm related cardiac arrest. Patients with no, moderate or severe circulatory failure were identified with cardiovascular Sequential Organ Failure Assessment at randomization. Primary outcome was the number of patients at day 7 with resolution of shock, accounting for the risk of death (competing risk analysis). Secondary endpoint included neurological outcome and death at day-90., Results: 584 patients were included in the analysis: 195 (34%), 46 (8%) and 340 (59%) had no, moderate and severe circulatory failure, respectively. Resolution of circulatory failure at day 7 was more frequently observed in the normothermia group than in the TTM group (60% [95 %CI 54-66] versus 53% [95 %CI 46-60], Gray-test: p = 0.016). The severity of circulatory failure at randomization was associated with its less frequent resolution at day 7 accounting for the risk of death (76 % [62-86] versus 54% [49-59] for patients with moderate versus severe circulatory failure, Gray test, p < 0.001, respectively). At day 90, the proportion of patients with Cerebral Performance Category score of 1 or 2 was lower in patients presenting severe circulatory failure (p = 0.038)., Conclusion: Circulatory failure is frequent after CA with non-shockable rhythm. Its severity at admission and TTM were associated with delayed resolution of circulatory failure., (© 2022 The Author(s).)

Purpose: This study aimed at evaluating the performance of Doppler-based resistive index (RI) and semi-quantitative evaluation of renal perfusion using color-Doppler (SQP) to predict de novo AKI in the subgroup of critically ill patients without AKI at admission., Methods: This study is an ancillary analysis of a prospective multicenter cohort study. Consecutive ICU patients requiring mechanical ventilation were included. Renal Doppler was performed at ICU admission. The diagnostic performance of RI and SQP to predict de novo AKI at day 3 was evaluated., Results: Among the 371 patients of the prospective cohort, 118 without AKI at study inclusion were included. Thirty-four patients (29%) developed an AKI. Neither RI (0.64 UI [0.57-0.70] vs 0.67 [0.62-0.70] in no AKI and de novo AKI group respectively, p = 0.177) nor SQP (2 [2, 3] vs 2 [1-3] in no AKI and de novo AKI group respectively, p = 0.061) were associated with AKI occurrence. Overall performance in predicting de novo AKI was null to poor with area under ROC curve of respectively 0.60 (95% CI 0.49-0.65) and 0.58 (95% CI 0.47-0.60) for RI and SQP. Similar results were obtained after adjustment for confounders., Conclusions: These results confirm the poor performance of Doppler-based indices in predicting renal prognosis of ICU patients., Competing Interests: Declaration of Competing Interest M.D. declare having received administrative support from his former institution (Saint-Etienne University Hospital) to conduct this study and having received research support from Astute Medical unrelated to the current study. Outside the scope of this study, MD declare having received grant from MSD, speaker fees from MSD, Astelas and Gilead-Kite and having attended an advisory board for Gilead-Kite. The other authors declare having no other conflict of interest related to this manuscript., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Rationale: Diaphragm dysfunction is frequently observed in critically ill patients with difficult weaning from mechanical ventilation. Objectives: To evaluate the effects of temporary transvenous diaphragm neurostimulation on weaning outcome and maximal inspiratory pressure. Methods: Multicenter, open-label, randomized, controlled study. Patients aged ⩾18 years on invasive mechanical ventilation for ⩾4 days and having failed at least two weaning attempts received temporary transvenous diaphragm neurostimulation using a multielectrode stimulating central venous catheter (bilateral phrenic stimulation) and standard of care (treatment) ( n  = 57) or standard of care (control) ( n  = 55). In seven patients, the catheter could not be inserted, and in seven others, pacing therapy could not be delivered; consequently, data were available for 43 patients. The primary outcome was the proportion of patients successfully weaned. Other endpoints were mechanical ventilation duration, 30-day survival, maximal inspiratory pressure, diaphragm-thickening fraction, adverse events, and stimulation-related pain. Measurements and Main Results: The incidences of successful weaning were 82% (treatment) and 74% (control) (absolute difference [95% confidence interval (CI)], 7% [-10 to 25]), P  = 0.59. Mechanical ventilation duration (mean ± SD) was 12.7 ± 9.9 days and 14.1 ± 10.8 days, respectively, P  = 0.50; maximal inspiratory pressure increased by 16.6 cm H 2 O and 4.8 cm H 2 O, respectively (difference [95% CI], 11.8 [5 to 19]), P  = 0.001; and right hemidiaphragm thickening fraction during unassisted spontaneous breathing was +17% and -14%, respectively, P  = 0.006, without correlation with changes in maximal inspiratory pressure. Serious adverse event frequency was similar in both groups. Median stimulation-related pain in the treatment group was 0 (no pain). Conclusions: Temporary transvenous diaphragm neurostimulation did not increase the proportion of successful weaning from mechanical ventilation. It was associated with a significant increase in maximal inspiratory pressure, suggesting reversal of the course of diaphragm dysfunction. Clinical trial registered with www.clinicaltrials.gov (NCT03096639) and the European Database on Medical Devices (CIV-17-06-020004).

Background and Aims: Coronavirus disease 2019 (COVID-19) is a serious public health issue that became rapidly pandemic. Liver injury and comorbidities, including metabolic syndrome, are associated with severe forms of the disease. This study sought to investigate liver injury, clinical features, and risk factors in patients with mild, moderate, and severe COVID-19., Methods: We retrospectively included all consecutive patients hospitalized with laboratory-confirmed COVID-19 between February, 22 and May 15, 2020 at the emergency rooms of a French tertiary hospital. Medical history, symptoms, biological and imaging data were collected., Results: Among the 1381 hospitalizations for COVID-19, 719 patients underwent liver tests on admission and 496 (68.9%) patients displayed abnormal liver tests. Aspartate aminotransferase was most commonly abnormal in 57% of cases, followed by gamma-glutamyl transferase, alanine aminotransferase, albumin, alkaline phosphatase, and total bilirubin in 56.5%, 35.9%, 18.4%, 11.4%, and 5.8%. The presence of hepatocellular type more than 2xULN was associated with a higher risk of hospitalization and a worse course of severe disease (odd ratio [OR] 5.599; 95%CI: 1.27-23.86; p = 0.021; OR 3.404; 95% CI: 2.12-5.47; p < 0.001, respectively). A higher NAFLD fibrosis score was associated with a higher risk of hospitalization (OR 1.754; 95%CI: 1.27-2.43, p < 0.001). In multivariate analyses, patients with high fibrosis-4 index had a 3-fold greater risk of severe disease (p < 0.001)., Conclusion: Abnormal liver tests are common in patients with COVID-19 and could predict the outcome. Patients with non-alcoholic fatty liver disease and liver fibrosis are at higher risk of progressing to severe COVID-19., (Copyright © 2022 Elsevier Masson SAS. All rights reserved.)

Background and Objectives: Cerebral complications related to the COVID-19 were documented by brain MRIs during the acute phase. The purpose of the present study was to describe the evolution of these neuroimaging findings (MRI and FDG-PET/CT) and describe the neurocognitive outcomes of these patients., Methods: During the first wave of the COVID-19 outbreak between 1 March and 31 May 2020, 112 consecutive COVID-19 patients with neurologic manifestations underwent a brain MRI at Strasbourg University hospitals. After recovery, during follow-up, of these 112 patients, 31 (initially hospitalized in intensive care units) underwent additional imaging studies (at least one brain MRI)., Results: Twenty-three men (74%) and eight women (26%) with a mean age of 61 years (range: 18-79) were included. Leptomeningeal enhancement, diffuse brain microhemorrhages, acute ischemic strokes, suspicion of cerebral vasculitis, and acute inflammatory demyelinating lesions were described on the initial brain MRIs. During follow-up, the evolution of the leptomeningeal enhancement was discordant, and the cerebral microhemorrhages were stable. We observed normalization of the vessel walls in all patients suspected of cerebral vasculitis. Four patients (13%) demonstrated new complications during follow-up (ischemic strokes, hypoglossal neuritis, marked increase in the white matter FLAIR hyperintensities with presumed vascular origin, and one suspected case of cerebral vasculitis). Concerning the grey matter volumetry, we observed a loss of volume of 3.2% during an average period of approximately five months. During follow-up, the more frequent FDG-PET/CT findings were hypometabolism in temporal and insular regions., Conclusion: A minority of initially severe COVID-19 patients demonstrated new complications on their brain MRIs during follow-up after recovery.

Background: Major adverse cardiovascular events among sepsis survivors is an emerging health issue. Because endothelial senescence leads to vascular dysfunction and atherothrombosis, sepsis could be associated to vascular stress-induced premature senescence and thus with long-term cardiovascular events., Materials & Methods: Adult Wistar male rats were submitted to cecal ligation and puncture, or a SHAM operation. Markers of inflammation, oxidative stress and endothelial senescence were assessed at 3, 7 and 90 days (D), and vascular reactivity was assessed in conductance and resistance vessels at D90. Expression of proteins involved in senescence and inflammation was assessed by Western blot analysis and confocal microscopy, oxidative stress by dihydroethidium probing., Results: Pro-inflammatory endothelial ICAM-1 and VCAM-1 were up-regulated by three-fold in CLP vs. SHAM at D7 and remained elevated at D90. Oxidative stress followed a similar pattern but was detected in the whole vascular wall. Sepsis accelerated premature senescence in aorta vascular tissue as shown by the significant up-regulation of p53 and down-stream p21 and p16 senescent markers at D7, values peaking at D90 whereas the absence of significant variation in activated caspase-3 confirmed p53 as a prime inducer of senescence. In addition, p53 was mainly expressed in the endothelium. Sepsis-induced long-term vascular dysfunction was confirmed in aorta and main mesenteric artery, with a major alteration of the endothelial-dependent nitric oxide pathway., Conclusions: Septic shock-induced long-term vascular dysfunction is associated with endothelial and vascular senescence. Our model could prove useful for investigating senotherapies aiming at reducing long-term cardiovascular consequences of septic shock., (Copyright © 2021. Published by Elsevier Inc.)

Among the long-term consequences of sepsis (also termed "post-sepsis syndrome") the increased risk of unexplained cardiovascular complications, such as myocardial infarction, acute heart failure or stroke, is one of the emerging specific health concerns. The vascular accelerated ageing also named premature senescence is a potential mechanism contributing to atherothrombosis, consequently leading to cardiovascular events. Indeed, vascular senescence-associated major adverse cardiovascular events (MACE) are a potential feature in sepsis survivors and of the elderly at cardiovascular risk. In these patients, accelerated vascular senescence could be one of the potential facilitating mechanisms. This review will focus on premature senescence in sepsis regardless of age. It will highlight and refine the potential relationships between sepsis and accelerated vascular senescence. In particular, key cellular mechanisms contributing to cardiovascular events in post-sepsis syndrome will be highlighted, and potential therapeutic strategies to reduce the cardiovascular risk will be further discussed., (© 2021. The Author(s).)

Background: In comatose patients receiving oro-tracheal intubation for mechanical ventilation (MV), the risk of aspiration is increased. Aspiration can lead to chemical pneumonitis (inflammatory reaction to the gastric contents), or aspiration pneumonia (infection caused by inhalation of microorganisms). Distinguishing between the two types is challenging. We tested the interest of using a decisional algorithm based on procalcitonin (PCT) values to guide initiation and discontinuation of antibiotic therapies in intubated patients., Methods: The PROPASPI (PROcalcitonin Pneumonia/pneumonitis Associated with ASPIration) trial is a multicenter, prospective, randomized, controlled, single-blind, superiority study comparing two strategies: (1) an intervention group where threshold PCT values were used to guide initiation and discontinuation of antibiotics (PCT group); and (2) a control group, where antibiotic therapy was managed at the physician's discretion. Patients aged 18 years or over, intubated for coma (Glasgow score ≤ 8), with MV initiated within 48 h after admission, were eligible. The primary endpoint was the duration of antibiotic treatment during the first 15 days after admission to the ICU., Results: From 24/2/2015 to 28/8/2019, 1712 patients were intubated for coma in the 5 participating centers, of whom 166 were included in the study. Data from 159 were available for intention-to-treat analysis: 81 in the PCT group, and 78 in the control group. Overall, 67 patients (43%) received antibiotics in the intensive care unit (ICU); there was no significant difference between groups (37 (46%) vs 30 (40%) for PCT vs control, p = 0.432). The mean duration of antibiotic treatment during the first 15 days in the ICU was 2.7 ± 3.8 days; there was no significant difference between groups (3.0 ± 4.1 days vs 2.3 ± 3.4 days for PCT vs control, p = 0.311). The mean number of days under MV was significantly higher in the PCT group (3.7 ± 3.6 days) than in controls (2.7 ± 2.5 days, p = 0.033). The duration of ICU stay was also significantly longer in the PCT group: 6.4 ± 6.5 days vs 4.6 ± 3.5 days in the control group (p = 0.043). After adjustment for SAPS II score, the difference in length of stay and duration of mechanical ventilation between groups was no longer significant., Conclusion: The use of PCT values to guide therapy, in comparison to the use of clinical, biological (apart from PCT) and radiological criteria, does not modify exposure to antibiotics in patients intubated for coma. Trial registration Clinicaltrials.gov Identifier NCT02862314., (© 2021. The Author(s).)

Introduction: Pre-emptive inhaled antibiotics may be effective to reduce the occurrence of ventilator-associated pneumonia among critically ill patients. Meta-analysis of small sample size trials showed a favourable signal. Inhaled antibiotics are associated with a reduced emergence of antibiotic resistant bacteria. The aim of this trial is to evaluate the benefit of a 3-day course of inhaled antibiotics among patients undergoing invasive mechanical ventilation for more than 3 days on the occurrence of ventilator-associated pneumonia., Methods and Analysis: Academic, investigator-initiated, parallel two group arms, double-blind, multicentre superiority randomised controlled trial. Patients invasively ventilated more than 3 days will be randomised to receive 20 mg/kg inhaled amikacin daily for 3 days or inhaled placebo (0.9% Sodium Chloride). Occurrence of ventilator-associated pneumonia will be recorded based on a standardised diagnostic framework from randomisation to day 28 and adjudicated by a centralised blinded committee., Ethics and Dissemination: The protocol and amendments have been approved by the regional ethics review board and French competent authorities (Comité de protection des personnes Ouest I, No.2016-R29). All patients will be included after informed consent according to French law. Results will be disseminated in international scientific journals., Trial Registration Numbers: EudraCT 2016-001054-17 and NCT03149640., Competing Interests: Competing interests: SE declares consultancies from Aerogen, La Diffusion Technique Française; unrestricted research grants from Fisher & Paykel Healthcare, Aerogen Ltd, Hamilton Medical; travel reimbursements from Aerogen and Fisher & Paykel Healthcare., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Septic shock and disseminated intravascular coagulation (DIC) are known to be characterized by an endothelial cell dysfunction. The molecular mechanisms underlying this relationship are, however, poorly understood. In this work, we aimed to investigate human circulating IFN-α in patients with septic shock-induced DIC and tested the potential role of endothelial Stat1 (signal transducer and activator of transcription 1) as a therapeutic target in a mouse model of sepsis. For this, circulating type I, type II, and type III IFNs and procoagulant microvesicles were quantified in a prospective cohort of patients with septic shock. Next, we used a septic shock model induced by cecal ligation and puncture in wild-type mice, in Ifnar1 (type I IFN receptor subunit 1)-knockout mice, and in Stat1 conditional knockout mice. In human samples, we observed higher concentrations of circulating IFN-α and IFN-α1 in patients with DIC compared with patients without DIC, whereas concentrations of IFN-β, IFN-γ, IFN-λ1, IFN-λ2, and IFN-λ3 were not different. IFN-α concentration was positively correlated with CD105 microvesicle concentrations, reflecting endothelial injury. In Ifnar1 -/- mice, cecal ligation and puncture did not induce septic shock and was characterized by lesser endothelial cell injury, with lower aortic inflammatory cytokine expression, endothelial inflammatory-related gene expression, and fibrinolysis. In mice in which Stat1 was specifically ablated in endothelial cells, a marked protection against sepsis was also observed, suggesting the relevance of an endothelium-targeted strategy. Our work highlights the key roles of type I IFNs as pathogenic players in septic shock-induced DIC and the potential pertinence of endothelial STAT1 as a therapeutic target.