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Abstract This retrospective study aimed to compare the mortality and burden of respiratory syncytial virus (RSV group), SARS-CoV-2 (COVID-19 group), non-H1N1 (Seasonal influenza group) and H1N1 influenza (H1N1 group) in adult patients admitted to intensive care unit (ICU) with respiratory failure. A total of 807 patients were included. Mortality was compared between the four following groups: RSV, COVID-19, seasonal influenza, and H1N1 groups. Patients in the RSV group had significantly more comorbidities than the other patients. At admission, patients in the COVID-19 group were significantly less severe than the others according to the simplified acute physiology score-2 (SAPS-II) and sepsis-related organ failure assessment (SOFA) scores. Using competing risk regression, COVID-19 (sHR = 1.61; 95% CI 1.10; 2.36) and H1N1 (sHR = 1.87; 95% CI 1.20; 2.93) were associated with a statistically significant higher mortality while seasonal influenza was not (sHR = 0.93; 95% CI 0.65; 1.31), when compared to RSV. Despite occurring in more severe patients, RSV and seasonal influenza group appear to be associated with a more favorable outcome than COVID-19 and H1N1 groups.

Abstract Background Prevalence, risk factors and medical management of persistent pain symptoms after critical care illness have not been thoroughly investigated. Methods We performed a prospective multicentric study in patients with an intensive care unit (ICU) length of stay ≥ 48 h. The primary outcome was the prevalence of significant persistent pain, defined as a numeric rating scale (NRS) ≥ 3, 3 months after admission. Secondary outcomes were the prevalence of symptoms compatible with neuropathic pain (ID-pain score > 3) and the risk factors of persistent pain. Results Eight hundred fourteen patients were included over a 10-month period in 26 centers. Patients had a mean age of 57 (± 17) years with a SAPS 2 score of 32 (± 16) (mean ± SD). The median ICU length of stay was 6 [4–12] days (median [interquartile]). At 3 months, the median intensity of pain symptoms was 2 [1–5] in the entire population, and 388 (47.7%) patients had significant pain. In this group, 34 (8.7%) patients had symptoms compatible with neuropathic pain. Female (Odds Ratio 1.5 95% CI [1.1–2.1]), prior use of anti-depressive agents (OR 2.2 95% CI [1.3–4]), prone positioning (OR 3 95% CI [1.4–6.4]) and the presence of pain symptoms on ICU discharge (NRS ≥ 3) (OR 2.4 95% CI [1.7–3.4]) were risk factors of persistent pain. Compared with sepsis, patients admitted for trauma (non neuro) (OR 3.5 95% CI [2.1–6]) were particularly at risk of persistent pain. Only 35 (11.3%) patients had specialist pain management by 3 months. Conclusions Persistent pain symptoms were frequent in critical illness survivors and specialized management remained infrequent. Innovative approaches must be developed in the ICU to minimize the consequences of pain. Trial registration. NCT04817696. Registered March 26, 2021.

Abstract Background Although multiple individual immune parameters have been demonstrated to predict the occurrence of secondary infection after critical illness, significant questions remain with regards to the selection, timing and clinical utility of such immune monitoring tests. Research question As a sub-study of the REALISM study, the REALIST score was developed as a pragmatic approach to help clinicians better identify and stratify patients at high risk for secondary infection, using a simple set of relatively available and technically robust biomarkers. Study design and methods This is a sub-study of a single-centre prospective cohort study of immune profiling in critically ill adults admitted after severe trauma, major surgery or sepsis/septic shock. For the REALIST score, five immune parameters were pre-emptively selected based on their clinical applicability and technical robustness. Predictive power of different parameters and combinations of parameters was assessed. The main outcome of interest was the occurrence of secondary infection within 30 days. Results After excluding statistically redundant and poorly predictive parameters, three parameters remained in the REALIST score: mHLA-DR, percentage of immature (CD10− CD16−) neutrophils and serum IL-10 level. In the cohort of interest (n = 189), incidence of secondary infection at day 30 increased from 8% for patients with REALIST score of 0 to 46% in patients with a score of 3 abnormal parameters, measured ad D5–7. When adjusted for a priori identified clinical risk factors for secondary infection (SOFA score and invasive mechanical ventilation at D5–7), a higher REALIST score was independently associated with increased risk of secondary infection (42 events (22.2%), adjusted HR 3.22 (1.09–9.50), p = 0.034) and mortality (10 events (5.3%), p = 0.001). Interpretation We derived and presented the REALIST score, a simple and pragmatic stratification strategy which provides clinicians with a clear assessment of the immune status of their patients. This new tool could help optimize care of these individuals and could contribute in designing future trials of immune stimulation strategies. Graphical Abstract

The strongly coupled hydrodynamic, magnetic, and radiation properties of the plasma in the solar chromosphere make it a region of the Sun's atmosphere that is poorly understood. We use data obtained with the high-resolution Visible Broadband Imager (VBI) equipped with an H β filter and the Visible Spectro-Polarimeter (ViSP) on the Daniel K. Inouye Solar Telescope to investigate the fine-scale structure of the plage chromosphere. To aid in the interpretation of the VBI imaging data, we also analyze spectra from the CHROMospheric Imaging Spectrometer on the Swedish Solar Telescope. The analysis of spectral properties, such as enhanced line widths and line depths, explains the high contrast of the fibrils relative to the background atmosphere demonstrating that H β is an excellent diagnostic for the enigmatic fine-scale structure of the chromosphere. A correlation between the parameters of the H β line indicates that opacity broadening created by overdense fibrils could be the main reason for the spectral line broadening frequently observed in chromospheric fine-scale structures. Spectropolarimetric inversions of the ViSP data in the Ca ii 8542 Å and Fe i 6301/6302 Å lines are used to construct semiempirical models of the plage atmosphere. Inversion outputs indicate the existence of dense fibrils in the Ca ii 8542 Å line. The analyses of the ViSP data show that the morphological characteristics, such as orientation, inclination, and length of fibrils, are defined by the topology of the magnetic field in the photosphere. Chromospheric maps reveal a prominent magnetic canopy in the area where fibrils are directed toward the observer.

We report commissioning observations of the Si x 1430 nm solar coronal line observed coronagraphically with the Cryogenic Near-Infrared Spectropolarimeter at the National Science Foundation’s Daniel K. Inouye Solar Telescope. These are the first known spatially resolved observations of this spectral line, which has strong potential as a coronal magnetic field diagnostic. The observations target a complex active region located on the solar northeast limb on 2022 March 4. We present a first analysis of these data that extracts the spectral line properties through a careful treatment of the variable atmospheric transmission that is known to impact this spectral window. Rastered images are created and compared with extreme-UV observations from the Solar Dynamics Observatory (SDO) Atmospheric Imaging Assembly (AIA) instrument. A method for estimating the electron density from the Si x observations is then demonstrated that makes use of the forbidden line density-sensitive emissivity and an emission-measure analysis of the SDO/AIA bandpass observations. In addition, we derive an effective temperature and nonthermal line width across the region. This study informs the calibration approaches required for more routine observations of this promising diagnostic line.

Abstract Background Morbidity and Mortality conference provides the necessary improvement measures for patient safety. However, they are an underused resource mainly because the conclusions to be drawn from the discussion and their implications for practice are not always well integrated by inpatient care teams. We therefore propose in this study two interventions to optimise their effectiveness: a passive feedback with wide dissemination by e-mail and/or on paper of the results of the Morbidity and Mortality conference to inpatient care teams and an active feedback with in situ inter-professional simulation-training programme in which scenarios will be based on cases studied in Morbidity and Mortality conference. In the present study, we hypothesise that the greatest reduction the occurrence of adverse event will be in the active feedback arm. Methods A cluster randomised controlled study will be performed at four study sites. The unit of randomisation is wards within the study sites. Fifteen wards will be randomly assigned to passive feedback, active feedback, or a standard MMC (control arm). Passive feedback and active feedback arms will be compared to standard arm in terms of occurrence of adverse events. The trigger tool methodology used to identify adverse events is a retrospective review of inpatient records using “triggers”: an adverse event is defined as a patient’s stay with at least one positive trigger. Discussion The in situ simulation training based on cases processed in Morbidity and Mortality conference is built according to the main topics identified for the successful implementation of healthcare simulation in patient safety programmes: technical skills, nontechnical skills, assessment, effectiveness, and system probing. The in situ simulation-training programme conducted as part of the study has the potential to improve patient safety during hospitalisation. We therefore expect the greatest reduction in the occurrence of adverse events in patients hospitalised in the active feedback arm. This expected result would have a direct impact on patient safety and would place in situ simulation at the highest level of the Kirkpatrick model. Trial registration Clinicaltrials.gov NCT02771613. Registered on May 12, 2016. All items from the WHO Trial Registration Data Set can be found within the protocol.

Introduction Previous studies demonstrated that the implementation of the Kidney Disease Improving Global Outcomes (KDIGO) guideline-based bundle, consisting of different supportive measures in patients at high risk for acute kidney injury (AKI), might reduce rate and severity of AKI after surgery. However, the effects of the care bundle in broader population of patients undergoing surgery require confirmation.Methods and analysis The BigpAK-2 trial is an international, randomised, controlled, multicentre trial. The trial aims to enrol 1302 patients undergoing major surgery who are subsequently admitted to the intensive care or high dependency unit and are at high-risk for postoperative AKI as identified by urinary biomarkers (tissue inhibitor of metalloproteinases 2*insulin like growth factor binding protein 7 (TIMP-2)*IGFBP7)). Eligible patients will be randomised to receive either standard of care (control) or a KDIGO-based AKI care bundle (intervention). The primary endpoint is the incidence of moderate or severe AKI (stage 2 or 3) within 72 hours after surgery, according to the KDIGO 2012 criteria. Secondary endpoints include adherence to the KDIGO care bundle, occurrence and severity of any stage of AKI, change in biomarker values during 12 hours after initial measurement of (TIMP-2)*(IGFBP7), number of free days of mechanical ventilation and vasopressors, need for renal replacement therapy (RRT), duration of RRT, renal recovery, 30-day and 60-day mortality, intensive care unit length-of-stay and hospital length-of-stay and major adverse kidney events. An add-on study will investigate blood and urine samples from recruited patients for immunological functions and kidney damage.Ethics and dissemination The BigpAK-2 trial was approved by the Ethics Committee of the Medical Faculty of the University of Münster and subsequently by the corresponding Ethics Committee of the participating sites. A study amendment was approved subsequently. In the UK, the trial was adopted as an NIHR portfolio study. Results will be disseminated widely and published in peer-reviewed journals, presented at conferences and will guide patient care and further research.Trial registration number NCT04647396.

Background: Candidemia is a major cause of mortality in the intensive care unit (ICU). According to the Infectious Diseases Society of America (IDSA), an echinocandin is recommended as initial therapy and fluconazole as an alternative. In a context of echinocandin resistance development, the question arising is whether azoles are a suitable alternative to echinocandins for the treatment of candidemia in critically ill patients. Methods: A 3-year (2015–2017) retrospective multicentric cohort study was conducted. Adult patients with a diagnosis of candidemia during the ICU stay and treated with echinocandins or azoles were included. Demographic, clinical data, mycological data, and antifungal treatments were collected. Kaplan–Meier survival analysis, univariate analysis, and a multivariate logistic regression analysis using a propensity score with the inverse probability of treatment weighting method were performed. Findings: Seventy-nine patients (n = 79) were analyzed. Treatment success, as well as survival on day 90 (Kaplan–Meier survival analysis, log rank test, p = 0.542), were comparable between patients who received echinocandins (caspofungin (n = 47)) or azoles (fluconazole (n = 29) or voriconazole (n = 3)). A multivariable analysis demonstrated that higher SOFA score on the day of candidemia diagnosis and absence of adequate Candida source control were independently associated with a greater risk of 90-day mortality, whereas azoles treatment was not associated with an excess 90-day mortality. Interpretation: This study confirms that the use of azoles recommended for candidemia, mostly fluconazole, as a first-line therapy is a reasonable alternative to caspofungin for ICU patients in our institution. This needs to be included in local guidelines through antifungal stewardship programs. Keywords: Candidemia, Caspofungin, Fluconazole, Voriconazole, Mortality, Propensity score

Introduction More than 300 million surgical procedures are performed each year. Acute kidney injury (AKI) is a common complication after major surgery and is associated with adverse short-term and long-term outcomes. However, there is a large variation in the incidence of reported AKI rates. The establishment of an accurate epidemiology of surgery-associated AKI is important for healthcare policy, quality initiatives, clinical trials, as well as for improving guidelines. The objective of the Epidemiology of Surgery-associated Acute Kidney Injury (EPIS-AKI) trial is to prospectively evaluate the epidemiology of AKI after major surgery using the latest Kidney Disease: Improving Global Outcomes (KDIGO) consensus definition of AKI.Methods and analysis EPIS-AKI is an international prospective, observational, multicentre cohort study including 10 000 patients undergoing major surgery who are subsequently admitted to the ICU or a similar high dependency unit. The primary endpoint is the incidence of AKI within 72 hours after surgery according to the KDIGO criteria. Secondary endpoints include use of renal replacement therapy (RRT), mortality during ICU and hospital stay, length of ICU and hospital stay and major adverse kidney events (combined endpoint consisting of persistent renal dysfunction, RRT and mortality) at day 90. Further, we will evaluate preoperative and intraoperative risk factors affecting the incidence of postoperative AKI. In an add-on analysis, we will assess urinary biomarkers for early detection of AKI.Ethics and dissemination EPIS-AKI has been approved by the leading Ethics Committee of the Medical Council North Rhine-Westphalia, of the Westphalian Wilhelms-University Münster and the corresponding Ethics Committee at each participating site. Results will be disseminated widely and published in peer-reviewed journals, presented at conferences and used to design further AKI-related trials.Trial registration number NCT04165369.

The Cryogenic Near-Infrared Spectropolarimeter (Cryo-NIRSP) is now conducting science operations at the National Science Foundation’s Daniel K. Inouye Solar Telescope (DKIST). We report results obtained during instrument commissioning that advance multiwavelength coronagraphic observations in the infrared. This includes the first observations of the Fe xiii 1075 nm, Fe xiii 1079 nm, Si x 1430 nm, and Si ix 3934 nm forbidden lines. The Si ix observations, in particular, significantly improve upon the few previous ground-based detections and open up this diagnostic for more routine study. We analyse long-slit spectra in each line sampling elongations from 1.06 to 1.52 solar radii above the northeast solar limb on 2022 February 14. Line characteristics as a function of radial distance are derived and discussed in comparison to modeled emission emergent from global coronal magnetohydrodynamic models with different heating prescriptions. We find favorable correspondence between the observations and different aspects of these models, and further demonstrate the utility of infrared observations for constraining coronal models. Continued DKIST/Cryo-NIRSP observations including polarimetric data, together with ongoing improvements in data calibrations, promise significant value for coronal studies.

Introduction With the spread of COVID-19 epidemic, health plans must be adapted continuously. There is an urgent need to define the best care courses of patients with COVID-19, especially in intensive care units (ICUs), according to their individualised benefit/risk ratio. Since older age is associated with poorer short-term and long-term outcomes, prediction models are needed, that may assist clinicians in their ICU admission decision. Senior-COVID-Rea was designed to evaluate, in patients over 60 years old admitted in ICU for severe COVID-19 disease, the impact of age and geriatric and paraclinical parameters on their mortality 30 days after ICU admission.Methods and analysis This is a multicentre survey protocol to be conducted in seven hospitals of the Auvergne-Rhône-Alpes region, France. All patients over 60 years old admitted in ICU for severe COVID-19 infection (or their legally acceptable representative) will be proposed to enter the study and to fill in a questionnaire regarding their functional and nutritional parameters 1 month before COVID-19 infection. Paraclinical parameters at ICU admission will be collected: lymphocytes and neutrophils counts, high-fluorescent lymphoid cells and immature granulocytes percentages (Sysmex data), D-dimers, C-reactive protein, lactate dehydrogenase (LDH), creatinine, CT scan for lung extension rate as well as clinical resuscitation scores, and the delay between the first signs of infection and ICU admission. The primary outcome will be the overall survival at day 30 post-ICU admission. The analysis of factors predicting mortality at day 30 will be carried out using univariate and multivariate logistic regressions. Multivariate logistic regression will consider up to 15 factors.The ambition of this trial, which takes into account the different approaches of geriatric vulnerability, is to define the respective abilities of different operational criteria of frailty to predict patients’ outcomes.Ethics and dissemination The study protocol was ethically approved. The results of the primary and secondary objectives will be published in peer-reviewed journals.Trial registration number NCT04422340.

Abstract Background Handoffs are a major determinant of patient’s safety but their implementation remains heterogeneous and non-standardized. Organizational factors, including the order in which individual cases are handled within the handoff, may play a role in their quality. We aimed to confirm the existence of the portfolio effect (e.g. a decrease in duration allocated to individual cases as the global handoff progresses) in ICU’s morning medical handoffs. Methods Two research assistants observed the morning handoffs in two ICUs (ICU-1, a 20-bed trauma and surgical ICU and ICU-2 a 10-bed medical and surgical ICU) within a university hospital, over a 6-month period. They were trained to measure the duration of each case (i.e., the handoff of a single patient). Patients’ socio-demographic and clinical data were extracted from electronic medical records. The effect of the case position within the global handoff on its duration was determined using a linear regression after log transformation of duration. The case position was categorized as either before or after the median position (first and second halves). Covariates clinically associated with handoff duration were included in the model (age, sex, Charlson comorbidities index, SAPS II score, number of organ supports, center (ICU-1 or ICU-2) and reason for admission). Results 2485 individual cases nested in 169 morning handoffs and related to 494 patients’ stays were observed. The mean (± SD) duration of the morning handoff was 60 minutes (± 12.5) in ICU-1 and 35.2 minutes (± 10.6) in ICU-2 with a mean number of cases presented of 18.9 (± 1.3) and 9.3 (± 1.0) respectively. The mean (± SD) duration of a case was 175 seconds (± 108). Trauma stays, patients severity and comorbidities, and the number of organ supports were associated with longer case handoffs. Asjusting for these covariates, cases in the second half were shorter compared to cases in the first half (RR 0.65, 95%CI (0.51 - 0.80)). Conclusions We confirmed the existence of a portfolio effect within ICU handoffs, emphasizing that interventions targeting handoffs’ improvement should focus on the content and the setting. We suggest avoiding the presentation of a same patient systematically at the end of the round.

Abstract The recent SarsCov2 pandemic has disrupted healthcare system notably impacting intensive care units (ICU). In severe cases, the immune system is dysregulated, associating signs of hyperinflammation and immunosuppression. In the present work, we investigated, using a joint modeling approach, whether the trajectories of cellular immunological parameters were associated with survival of COVID‐19 ICU patients. This study is based on the REA‐IMMUNO‐COVID cohort including 538 COVID‐19 patients admitted to ICU between March 2020 and May 2022. Measurements of monocyte HLA‐DR expression (mHLA‐DR), counts of neutrophils, of total lymphocytes, and of CD4+ and CD8+ subsets were performed five times during the first month after ICU admission. Univariate joint models combining survival at day 28 (D28), hospital discharge and longitudinal analysis of those biomarkers’ kinetics with mixed‐effects models were performed prior to the building of a multivariate joint model. We showed that a higher mHLA‐DR value was associated with a lower risk of death. Predicted mHLA‐DR nadir cutoff value that maximized the Youden index was 5414 Ab/C and led to an AUC = 0.70 confidence interval (95%CI) = [0.65; 0.75] regarding association with D28 mortality while dynamic predictions using mHLA‐DR kinetics until D7, D12 and D20 showed AUCs of 0.82 [0.77; 0.87], 0.81 [0.75; 0.87] and 0.84 [0.75; 0.93]. Therefore, the final joint model provided adequate discrimination performances at D28 after collection of biomarker samples until D7, which improved as more samples were collected. After severe COVID‐19, decreased mHLA‐DR expression is associated with a greater risk of death at D28 independently of usual clinical confounders.

Abstract Sepsis induces intense, dynamic and heterogeneous host response modulations. Despite improvement of patient management, the risk of mortality and healthcare-associated infections remains high. Treatments to counterbalance immune response are under evaluation, but effective biomarkers are still lacking to perform patient stratification. The design of the present study was defined to alleviate the limitations of existing literature: we selected patients who survived the initial hyperinflammatory response and are still hospitalized at day 5–7 after ICU admission. Using the Immune Profiling Panel (IPP), a fully automated RT-qPCR multiplex prototype, we optimized a machine learning model combining the IPP gene expression levels for the identification of patients at high risk of worsening, a composite endpoint defined as death or secondary infection, within one week after sampling. This was done on 332 sepsis patients selected from two retrospective studies. The IPP model identified a high-risk group comprising 30% of patients, with a significant increased proportion of worsening events at day 28 compared to the low-risk group (49% vs. 28%, respectively). These preliminary results underline the potential clinical application of IPP for sepsis patient stratification in a personalized medicine perspective, that will be confirmed in a larger prospective multicenter study.

Abstract Objective structured clinical examination (OSCE) is a valid method to evaluate medical students’ competencies. The present cross-sectional study aimed at determining how students’ coping and health-related behaviors are associated with their psychological well-being and performance on the day of the OSCE. Fourth-year medical students answered a set of standardized questionnaires assessing their coping (BCI) and health-related behaviors before the examination (sleep PSQI, physical activity GPAQ). Immediately before the OSCE, they reported their level of instant psychological well-being on multi-dimensional visual analogue scales. OSCE performance was assessed by examiners blinded to the study. Associations were explored using multivariable linear regression models. A total of 482 students were included. Instant psychological well-being was positively associated with the level of positive thinking and of physical activity. It was negatively associated with the level of avoidance and of sleep disturbance. Furthermore, performance was negatively associated with the level of avoidance. Positive thinking, good sleep quality, and higher level of physical activity were all associated with improved well-being before the OSCE. Conversely, avoidance coping behaviors seem to be detrimental to both well-being and OSCE performance. The recommendation is to pay special attention to students who engage in avoidance and to consider implementing stress management programs. Clinical trial: The study protocol was registered on clinicaltrial.gov NCT05393206, date of registration: 11 June 2022.

Abstract Background A 10-day dexamethasone regimen has emerged as the internationally adopted standard-of-care for severe COVID-19 patients. However, the immune response triggered by SARS-CoV-2 infection remains a complex and dynamic phenomenon, leading to various immune profiles and trajectories. The immune status of severe COVID-19 patients following complete dexamethasone treatment has yet to be thoroughly documented. Results To analyze monocyte HLA-DR expression (mHLA-DR) and CD4 + T lymphocyte count (CD4) in critically ill COVID-19 patients after a dexamethasone course and evaluate their association with 28-day ICU mortality, adult COVID-19 patients (n = 176) with an ICU length of stay of at least 10 days and under dexamethasone treatment were included. Associations between each biomarker value (or in combination) measured at day 10 after ICU admission and 28-day mortality in ICU were evaluated. At day 10, the majority of patients presented decreased values of both parameters. A significant association between low mHLA-DR and 28-day mortality was observed. This association remained significant in a multivariate analysis including age, comorbidities or pre-existing immunosuppression (adjusted Hazard ratio (aHR) = 2.86 [1.30–6.32], p = 0.009). Similar results were obtained with decreased CD4 + T cell count (aHR = 2.10 [1.09–4.04], p = 0.027). When combining these biomarkers, patients with both decreased mHLA-DR and low CD4 presented with an independent and significant elevated risk of 28-day mortality (i.e., 60%, aHR = 4.83 (1.72–13.57), p = 0.001). Conclusions By using standardized immunomonitoring tools available in clinical practice, it is possible to identify a subgroup of patients at high risk of mortality at the end of a 10-day dexamethasone treatment. This emphasizes the significance of integrating immune monitoring into the surveillance of intensive care patients in order to guide further immumodulation approaches.

Abstract Background Up to 42% of patients develop acute kidney injury (AKI) after cardiac surgery. The aim of this study was to describe the relationship between preoperative microcirculatory function and postoperative AKI after cardiac surgery using cardiopulmonary bypass (CPB). Methods The prospective observational cohort MONS enrolled 60 patients scheduled for valvular (n = 30, 50%) or coronary (n = 30, 50%) surgery using CPB. Preoperative microcirculation was assessed during preoperative consultation from January 2019 to April 2019 at the University Hospital of Angers, France, using endothelium-dependent and endothelium-independent reactivity tests on the forearm (iontophoresis of acetylcholine (ACh) and sodium nitroprusside (SNP), respectively). Skin blood flow was measured by laser speckle contrast imaging. The primary endpoint was the occurrence of AKI according to the KDIGO classification during the hospital stay. Results Forty-three (71.7%) patients developed AKI during the in-hospital follow-up, and 15 (25%) were classified as KDIGO stage 1, 20 (33%) KDIGO stage 2, and 8 (13%) KDIGO stage 3. Regarding preoperative microcirculation, a higher peak amplitude of vasodilation in response to iontophoresis of ACh was found in patients with postoperative occurrence of AKI (35 [20–49] vs 23 [9–44] LSPU, p = 0.04). Iontophoresis of SNP was not significantly different according to AKI occurrence (34 [22–49] vs 36 [20–50] LSPU, p = 0.95). In a multivariable model, the preoperative peak amplitude at iontophoresis of ACh was independently associated with postoperative AKI (OR 1.045 [1.001–1.092], p = 0.045). Conclusions The preoperative peak amplitude of endothelium-dependent vasodilation is independently associated with the postoperative occurrence of AKI. Trial registration Clinical-Trials.gov, NCT03631797. Registered 15 August 2018, https://clinicaltrials.gov/ct2/show/NCT03631797

BackgroundAbout 10–20% of pancreas allografts are still lost in the early postoperative period despite the identification of numerous detrimental risk factors that correlate with graft thrombosis.MethodsWe conducted a multicenter study including 899 pancreas transplant recipients between 2000 and 2018. Early pancreas failure due to complete thrombosis, long-term pancreas, kidney and patient survivals were analyzed and adjusted to donor, recipient and perioperative variables using a multivariate cause-specific Cox model stratified to transplant centers.ResultsPancreas from donors with history of hypertension (6.7%), as well as with high body mass index (BMI), were independently associated with an increased risk of pancreas failure within the first 30 post-operative days (respectively, HR= 2.57, 95% CI from 1.35 to 4.89 and HR= 1.11, 95% CI from 1.04 to 1.19). Interaction term between hypertension and BMI was negative. Donor hypertension also impacted long-term pancreas survival (HR= 1.88, 95% CI from 1.13 to 3.12). However, when pancreas survival was calculated after the postoperative day 30, donor hypertension was no longer a significant risk factor (HR= 1.22, 95% CI from 0.47 to 3.15). A lower pancreas survival was observed in patients receiving a pancreas from a hypertensive donor without RAAS (Renin Angiotensin Aldosterone System) blockers compared to others (50% vs 14%, p < 0.001). Pancreas survival was similar among non-hypertensive donors and hypertensive ones under RAAS blockers.ConclusionDonor hypertension was a significant and independent risk factor of pancreas failure. The well-known pathogenic role of renin-angiotensin-aldosterone system seems to be involved in the genesis of this immediate graft failure.

Abstract Purpose The present study aimed at assessing the prevalences of post-traumatic stress disorder (PTSD) (main objective), anxiety, depression, and burnout syndrome (BOS) and their associated factors in intensive care unit (ICU) staff workers in the second year of the COVID-19 pandemic. Materials and methods An international cross-sectional multicenter ICU-based online survey was carried out among the ICU staff workers in 20 ICUs across 3 continents. ICUs staff workers (both caregivers and non-caregivers) were invited to complete PCL-5, HADS, and MBI questionnaires for assessing PTSD, anxiety, depression, and the different components of BOS, respectively. A personal questionnaire was used to isolate independent associated factors with these disorders. Results PCL-5, HADS, and MBI questionnaires were completed by 585, 570, and 539 responders, respectively (525 completed all questionnaires). PTSD was diagnosed in 98/585 responders (16.8%). Changing familial environment, being a non-caregiver staff worker, having not being involved in a COVID-19 patient admission, having not been provided with COVID-19-related information were associated with PTSD. Anxiety was reported in 130/570 responders (22.8%). Working in a public hospital, being a woman, being financially impacted, being a non-clinical healthcare staff member, having no theoretical or practical training on individual preventive measures, and fear of managing COVID-19 patients were associated with anxiety. Depression was reported in 50/570 responders (8.8%). Comorbidity at risk of severe COVID-19, working in a public hospital, looking after a child, being a non-caregiver staff member, having no information, and a request for moving from the unit were associated with depression. Having received no information and no adequate training for COVID-19 patient management were associated with all 3 dimensions of BOS. Conclusion The present study confirmed that ICU staff workers, whether they treated COVID-19 patients or not, have a substantial prevalence of psychological disorders.

Abstract Background Although Acute Kidney Injury (AKI) incidence is increasing worldwide, data investigating its cost are lacking. This population-wide study aimed to describe the characteristics and costs of hospital stays with, and without AKI, and to estimate the AKI-associated increases in costs and length of stay (LOS) in three subgroups (major open visceral surgery (MOV), cardiovascular surgery with extracorporeal circulation (CVEC), and sepsis). Methods All hospital stays that occurred in France in 2018 were included. Stay and patient characteristics were collected in the French hospital discharge database and described. Medical conditions were identified using the 10th International Classification of Diseases and the medical acts classification. In each subgroup, the adjusted increase in cost and LOS associated with AKI was estimated using a generalized linear model with gamma distribution and a log link function. Results 26,917,832 hospital stays, of which 415,067 (1.5%) with AKI, were included. AKI was associated with 83,553 (19.8%), 7,165 (17.9%), and 15,387 (9.2%) of the stays with sepsis, CVEC, and MOV, respectively. Compared to stays without AKI, stays with AKI were more expensive (median [IQR] €4,719[€2,963-€7782] vs. €735[€383-€1,805]) and longer (median [IQR] 9[4–16] vs. 0[0–2] days). AKI was associated with a mean [95%CI] increase in hospitalization cost of 70% [69;72], 48% [45;50], and 68% [65;70] in the sepsis, CVEC, and MOV groups respectively, after adjustment. Conclusion This study confirms the major economic burden of in-hospital AKI in a developed country. Interventions to prevent AKI are urgently needed and their cost should be balanced with AKI-related costs.

Abstract Background The embedded participant (EP) plays a key role during a full scale/high-fidelity simulation (HFS) session. He/she is expected to guide the learner towards the achievement of the educational objectives of the scenario. However, his/her influence on learners’ performance stands undetermined and this effect remains briefly addressed in the literature. This study primarily aims to assess whether the EP could have an influence on the performance of the learner during a HFS scenario. The secondary aim was to establish an inventory of the EP practices in France. Methods This retrospective study was conducted in Lyon Claude Bernard University Health Simulation Centre (France). Anaesthesia and critical care residents in postgraduate years 1 to 5 who were scheduled for their HFS sessions during the 2016 to 2021 academic years were included. Two investigators independently evaluated the resident performance regarding both technical and non-technical skills from video recordings. In addition, a nationwide survey was sent out by email through the networks of the Francophone Healthcare Simulation Society (SoFraSimS, Société Francophone de Simulation en Santé) to collect information on EP practices in French-speaking Simulation centres. Results From a total of 344 HFS videos analysed, a cohort of 19 experienced EPs was identified. The EPs had an influence on the technical and non-technical performances of the learners. The 147 responses to the survey showed that predefined rules of EP good practice existed in only 36% of the simulation centres and 65% of respondents believed that specific EP training would be justified. Conclusion The EP can exert an influence on the performance of the learners during HFS. For acting as an EP, a great variability of practices and a lack of training are reported by professionals working in simulation centres. These results suggest that more attention must be paid to EP training and attitudes during simulation, especially if summative simulations are extensively developed.

Abstract Background The development of stratification tools based on the assessment of circulating mRNA of genes involved in the immune response is constrained by the heterogeneity of septic patients. The aim of this study is to develop a transcriptomic score based on a pragmatic combination of immune-related genes detected with a prototype multiplex PCR tool. Methods As training cohort, we used the gene expression dataset obtained from 176 critically ill patients enrolled in the REALISM study (NCT02638779) with various etiologies and still hospitalized in intensive care unit (ICU) at day 5–7. Based on the performances of each gene taken independently to identify patients developing ICU-acquired infections (ICU-AI) after day 5–7, we built an unweighted score assuming the independence of each gene. We then determined the performances of this score to identify a subgroup of patients at high risk to develop ICU-AI, and both longer ICU length of stay and mortality of this high-risk group were assessed. Finally, we validated the effectiveness of this score in a retrospective cohort of 257 septic patients. Results This transcriptomic score (TScore) enabled the identification of a high-risk group of patients (49%) with an increased rate of ICU-AI when compared to the low-risk group (49% vs. 4%, respectively), with longer ICU length of stay (13 days [95% CI 8–30] vs. 7 days [95% CI 6–9], p

Abstract The present study aimed at investigating the influence of personality on both anticipatory stress vulnerability and the effectiveness of coping strategies in an occupational stressful context. Following assessment of individual personality traits (Big Five Inventory), 147 volunteers were exposed to the anticipation of a stressful event. Anxiety and cardiac reactivity were assessed as markers of vulnerability to anticipatory stress. Participants were then randomly assigned to three groups and subjected to a 5-min intervention: relaxation breathing, relaxation breathing combined with cardiac biofeedback, and control. The effectiveness of coping interventions was determined through the cardiac coherence score achieved during the intervention. Higher neuroticism was associated with higher anticipatory stress vulnerability, whereas higher conscientiousness and extraversion were related to lower anticipatory stress vulnerability. Relaxation breathing and biofeedback coping interventions contributed to improve the cardiac coherence in all participants, albeit with greater effectiveness in individuals presenting higher score of openness to experience. The present findings demonstrated that personality traits are related to both anticipatory stress vulnerability and effectiveness of coping interventions. These results bring new insights into practical guidelines for stress prevention by considering personality traits. Specific practical applications for health professionals, who are likely to manage stressful situations daily, are discussed.

OBJECTIVES:. To determine the feasibility, safety, and efficacy of a biomarker-guided implementation of a kidney-sparing sepsis bundle (KSSB) of care in comparison with standard of care (SOC) on clinical outcomes in patients with sepsis. DESIGN:. Adaptive, multicenter, randomized clinical trial. SETTING:. Five University Hospitals in Europe and North America. PATIENTS:. Adult patients, admitted to the ICU with an indwelling urinary catheter and diagnosis of sepsis or septic shock, without acute kidney injury (acute kidney injury) stage 2 or 3 or chronic kidney disease. INTERVENTIONS:. A three-level KSSB based on Kidney Disease: Improving Global Outcomes (KDIGOs) recommendations guided by serial measurements of urinary tissue inhibitor of metalloproteinases-2 and insulin-like growth factor-binding protein 7 used as a combined biomarker [TIMP2]•[IGFBP7]. MEASUREMENTS AND MAIN RESULTS:. The trial was stopped for low enrollment related to the COVID-19 pandemic. Nineteen patients enrolled in five sites over 12 months were randomized to the SOC (n = 8, 42.0%) or intervention (n = 11, 58.0%). The primary outcome was feasibility, and key secondary outcomes were safety and efficacy. Adherence to protocol in patients assigned to the first two levels of KSSB was 15 of 19 (81.8%) and 19 of 19 (100%) but was 1 of 4 (25%) for level 3 KSSB. Serious adverse events were more frequent in the intervention arm (4/11, 36.4%) than in the control arm (1/8, 12.5%), but none were related to study interventions. The secondary efficacy outcome was a composite of death, dialysis, or progression of greater than or equal to 2 stages of acute kidney injury within 72 hours after enrollment and was reached by 3 of 8 (37.5%) patients in the control arm, and 0 of 11 (0%) patients in the intervention arm. In the control arm, two patients experienced progression of acute kidney injury, and one patient died. CONCLUSIONS:. Although the COVID-19 pandemic impeded recruitment, the actual implementation of a therapeutic strategy that deploys a KDIGO-based KSSB of care guided by risk stratification using urinary [TIMP2]•[IGFBP7] seems feasible and appears to be safe in patients with sepsis.

Abstract Background Active participation in high-fidelity simulation remains stressful for residents. Increased stress levels elicited during such simulation impacts performance. We tested whether relaxing breathing, paired or not with cardiac biofeedback, could lead to enhanced performance of residents during simulation. Methods This randomized pilot study involved the fifth-year anesthesiology and critical care residents who participated in high-fidelity at Lyon medical simulation center in 2019. Residents were randomized into three parallel interventions: relaxing breathing, relaxing breathing paired with cardiac biofeedback, and control. Each intervention was applied for five minutes immediately after the scenario briefing. The primary endpoint was the overall performance during the simulation rated by two blinded independent investigators. The secondary endpoints included component scores of overall performance and changes in psychological states. Results Thirty-four residents were included. Compared to the control group, residents in the relaxing breathing (+ 7%, 98.3% CI: 0.3 to 13.7, P = 0.013) and relaxing breathing paired with cardiac biofeedback (+ 8%, 98.3% CI: 0.82 to 14.81, P = 0.009) groups had a higher overall performance score. Following the interventions, compared to the control group, stress level was lower when participants had performed relaxing breathing alone (P = 0.029) or paired with biofeedback (P = 0.035). The internal relaxation level was higher in both the relaxing breathing alone (P = 0.016) and paired with biofeedback groups (P = 0.035). Conclusions Performing five minutes of relaxing breathing before the scenario resulted in better overall simulation performance. These preliminary findings suggest that short breathing interventions are effective in improving performance during simulation. Trial registration The study protocol was retrospectively registered on clinicaltrials.gov ( NCT04141124 , 28/10/2019).

Abstract Background Lymphopenia is a hallmark of severe coronavirus disease 19 (COVID-19). Similar alterations have been described in bacterial sepsis and therapeutic strategies targeting T cell function such as recombinant human interleukin 7 (rhIL-7) have been proposed in this clinical context. As COVID-19 is a viral sepsis, the objectives of this study were to characterize T lymphocyte response over time in severe COVID-19 patients and to assess the effect of ex vivo administration of rhIL-7. Results Peripheral blood mononuclear cells from COVID-19 patients hospitalized in intensive care unit (ICU) were collected at admission and after 20 days. Transcriptomic profile was evaluated through NanoString technology. Inhibitory immune checkpoints expressions were determined by flow cytometry. T lymphocyte proliferation and IFN-γ production were evaluated after ex vivo stimulation in the presence or not of rhIL-7. COVID-19 ICU patients were markedly lymphopenic at admission. Mononuclear cells presented with inhibited transcriptomic profile prevalently with impaired T cell activation pathways. CD4 + and CD8 + T cells presented with over-expression of co-inhibitory molecules PD-1, PD-L1, CTLA-4 and TIM-3. CD4 + and CD8 + T cell proliferation and IFN-γ production were markedly altered in samples collected at ICU admission. These alterations, characteristic of a T cell exhaustion state, were more pronounced at ICU admission and alleviated over time. Treatment with rhIL-7 ex vivo significantly improved both T cell proliferation and IFN-γ production in cells from COVID-19 patients. Conclusions Severe COVID-19 patients present with features of profound T cell exhaustion upon ICU admission which can be reversed ex vivo by rhIL-7. These results reinforce our understanding of severe COVID-19 pathophysiology and opens novel therapeutic avenues to treat such critically ill patients based of immunomodulation approaches. Defining the appropriate timing for initiating such immune-adjuvant therapy in clinical setting and the pertinent markers for a careful selection of patients are now warranted to confirm the ex vivo results described so far. Trial registration ClinicalTrials.gov identifier: NCT04392401 Registered 18 May 2020, http:// clinicaltrials.gov/ct2/show/NCT04392401.

OBJECTIVES:. Sepsis-acquired immunosuppression may play a major role in patients’ prognosis through increased risk of secondary infections. Triggering receptor expressed on myeloid cells 1 (TREM-1) is an innate immune receptor involved in cellular activation. Its soluble form (sTREM-1) has been described as a robust marker of mortality in sepsis. The objective of this study was to evaluate its association with the occurrence of nosocomial infections alone or in combination with human leucocyte antigen-DR on monocytes (mHLA-DR). DESIGN:. Observational study. SETTING:. University Hospital in France. PATIENTS:. One hundred sixteen adult septic shock patients as a post hoc study from the IMMUNOSEPSIS cohort (NCT04067674). INTERVENTIONS:. None. MEASUREMENTS AND MAIN RESULTS:. Plasma sTREM-1 and monocyte HLA-DR were measured at day 1 or 2 (D1/D2), D3/D4, and D6/D8 after admission. Associations with nosocomial infection were evaluated through multivariable analyses. At D6/D8, both markers were combined, and association with increased risk of nosocomial infection was evaluated in the subgroup of patients with most deregulated markers in a multivariable analysis with death as a competing risk. Significantly decreased mHLA-DR at D6/D8 and increased sTREM-1 concentrations were measured at all time points in nonsurvivors compared with survivors. Decreased mHLA-DR at D6/D8 was significantly associated with increased risk of secondary infections after adjustment for clinical parameters with a subdistribution hazard ratio of 3.61 (95% CI, 1.39–9.34; p = 0.008). At D6/D8, patients with persistently high sTREM-1 and decreased mHLA-DR presented with a significantly increased risk of infection (60%) compared with other patients (15.7%). This association remained significant in the multivariable model (subdistribution hazard ratio [95% CI], 4.65 [1.98–10.9]; p < 0.001). CONCLUSIONS:. In addition to its prognostic interest on mortality, sTREM-1, when combined with mHLA-DR, may help to better identify immunosuppressed patients at risk of nosocomial infections.

Abstract Background We investigated the impact of the COVID-19 crisis on mental health of professionals working in the intensive care unit (ICU) according to the intensity of the epidemic in France. Methods This cross-sectional survey was conducted in 77 French hospitals from April 22 to May 13 2020. All ICU frontline healthcare workers were eligible. The primary endpoint was the mental health, assessed using the 12-item General Health Questionnaire. Sources of stress during the crisis were assessed using the Perceived Stressors in Intensive Care Units (PS-ICU) scale. Epidemic intensity was defined as high or low for each region based on publicly available data from Santé Publique France. Effects were assessed using linear mixed models, moderation and mediation analyses. Results In total, 2643 health professionals participated; 64.36% in high-intensity zones. Professionals in areas with greater epidemic intensity were at higher risk of mental health issues (p