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BACKGROUND: The immune response of critically ill patients, such as those with sepsis, severe trauma, or major surgery, is heterogeneous and dynamic, but its characterization and impact on outcomes are poorly understood. Until now, the primary challenge in advancing our understanding of the disease has been to concurrently address both multiparametric and temporal aspects. METHODS: We used a clustering method to identify distinct groups of patients, based on various immune marker trajectories during the first week after admission to ICU. In 339 severely injured patients, we initially longitudinally clustered common biomarkers (both soluble and cellular parameters), whose variations are well-established during the immunosuppressive phase of sepsis. We then applied this multi-trajectory clustering using markers composed of whole blood immune-related mRNA. RESULTS: We found that both sets of markers revealed two immunotypes, one of which was associated with worse outcomes, such as increased risk of hospital-acquired infection and mortality, and prolonged hospital stays. This immunotype showed signs of both hyperinflammation and immunosuppression, which persisted over time. CONCLUSION: Our study suggest that the immune system of critically ill patients can be characterized by two distinct longitudinal immunotypes, one of which included patients with a persistently dysregulated and impaired immune response. This work confirms the relevance of such methodology to stratify patients and pave the way for further studies using markers indicative of potential immunomodulatory drug targets.
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Biomarcadores , Ferimentos e Lesões , Humanos , Masculino , Feminino , Biomarcadores/sangue , Biomarcadores/análise , Pessoa de Meia-Idade , Adulto , Ferimentos e Lesões/imunologia , Ferimentos e Lesões/sangue , Análise por Conglomerados , Estado Terminal , Unidades de Terapia Intensiva/estatística & dados numéricos , Unidades de Terapia Intensiva/organização & administração , Idoso , Sepse/sangue , Sepse/imunologia , Estudos LongitudinaisRESUMO
BACKGROUND: Acute kidney injury (AKI) is common in hospitalized patients and results in significant morbidity and mortality. The objective of the study was to explore the systemic immune response of intensive care unit patients presenting with AKI, especially the association between immune profiles and persistent AKI during the first week after admission following various types of injuries (sepsis, trauma, surgery, and burns). METHODS: REALAKI is an ancillary analysis of the REAnimation Low Immune Status Marker (REALISM) cohort study, in which 359 critically ill patients were enrolled in three different intensive care units. Patients with end-stage renal disease were excluded from the REALAKI study. Clinical samples and data were collected three times after admission: at day 1 or 2 (D1-2), day 3 or 4 (D3-4) and day 5, 6 or 7 (D5-7). Immune profiles were compared between patients presenting with or without AKI. Patients with AKI at both D1-2 and D5-7 were defined as persistent AKI. A multivariable logistic regression model was performed to determine the independent association between AKI and patients' immunological parameters. RESULTS: Three hundred and fifty-nine patients were included in this analysis. Among them, 137 (38%) were trauma patients, 103 (29%) post-surgery patients, 95 (26%) sepsis patients, and 24 (7%) were burn patients. One hundred and thirty-nine (39%) patients presented with AKI at D1-2 and 61 (20%) at D5-7. Overall, 94% presented with persistent AKI at D5-7. Patients with AKI presented with increased pro and anti-inflammatory cytokines and altered innate and adaptive immune responses. The modifications observed in the immune profiles tended to be more pronounced with increasing KDIGO stages. In the logistic regression model, a statistically significant association was observed at D1-2 between AKI and CD10lowCD16low immature neutrophils (OR 3.03 [1.7-5.5]-p < 0.001). At D5-7, increased interleukin-10 (IL-10) levels and reduced ex vivo TNF-α production after LPS stimulation were significantly associated with the presence of AKI (OR 1.38 [1.12-1.71]-p = 0.001 and 0.51 [0.27-0.91]-p = 0.03, respectively). Patients who recovered from AKI between D1-2 and D5-7 compared to patients with persistent AKI at D5-7, tended to correct these alterations. CONCLUSION: Following various types of severe injuries, early AKI is associated with the initial inflammatory response. Presence of AKI at the end of the first week after injury is associated with injury-induced immunosuppression.
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Injúria Renal Aguda , Estado Terminal , Humanos , Masculino , Injúria Renal Aguda/imunologia , Injúria Renal Aguda/etiologia , Feminino , Pessoa de Meia-Idade , Idoso , Adulto , Estudos de Coortes , Unidades de Terapia Intensiva/estatística & dados numéricos , Unidades de Terapia Intensiva/organização & administração , Ferimentos e Lesões/complicações , Ferimentos e Lesões/imunologia , Estudos Prospectivos , Fatores de Tempo , Biomarcadores/sangue , Biomarcadores/análise , Sepse/complicações , Sepse/imunologiaRESUMO
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.
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COVID-19 , Antígenos HLA-DR , Monócitos , Humanos , COVID-19/mortalidade , COVID-19/imunologia , Masculino , Feminino , Monócitos/metabolismo , Monócitos/imunologia , Pessoa de Meia-Idade , Idoso , Unidades de Terapia Intensiva , SARS-CoV-2 , Biomarcadores/sangue , Índice de Gravidade de DoençaRESUMO
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.
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Biomarcadores , Sepse , Humanos , Sepse/imunologia , Masculino , Feminino , Idoso , Pessoa de Meia-Idade , Aprendizado de Máquina , Estudos Retrospectivos , PrognósticoRESUMO
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.
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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.
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Adaptação Psicológica , Estudantes de Medicina , Humanos , Estudantes de Medicina/psicologia , Feminino , Masculino , Estudos Transversais , Inquéritos e Questionários , Adulto , Adulto Jovem , Comportamentos Relacionados com a Saúde , Competência Clínica , Exercício Físico/psicologia , Avaliação Educacional/métodosRESUMO
Adsorption-based extracorporeal therapies have been subject to technical developments and clinical application for close to five decades. More recently, new technological developments in membrane and sorbent manipulation have made it possible to deliver more biocompatible extracorporeal adsorption therapies to patients with a variety of conditions. There are several key rationales based on physicochemical principles and clinical considerations that justify the application and investigation of such therapies as evidenced by multiple ex-vivo, experimental, and clinical observations. Accordingly, unspecific adsorptive extracorporeal therapies have now been applied to the treatment of a wide array of conditions from poisoning to drug overdoses, to inflammatory states and sepsis, and acute or chronic liver and kidney failure. In response to the rapidly expanding knowledge base and increased clinical evidence, we convened an Acute Disease Quality Initiative (ADQI) consensus conference dedicated to such treatment. The data show that hemoadsorption has clinically acceptable short-term biocompatibility and safety, technical feasibility, and experimental demonstration of specified target molecule removal. Pilot studies demonstrate potentially beneficial effects on physiology and larger studies of endotoxin-based hemoadsorption have identified possible target phenotypes for larger randomized controlled trials (RCTs). Moreover, in a variety of endogenous and exogenous intoxications, removal of target molecules has been confirmed in vivo. However, some studies have raised concerns about harm or failed to deliver benefits. Thus, despite many achievements, modern hemoadsorption remains a novel and experimental intervention with limited data, and a large research agenda.
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PURPOSE: Personality traits are associated with psychophysiological stress, but few studies focus on medical students. This study aimed to better understand the association of personality traits with the efficacy of stress management interventions for medical students. METHOD: A randomized controlled trial was conducted with fourth-year students who took the objective structured clinical examination at Bernard University Lyon 1 in December 2021. Students were randomized in cardiac biofeedback, mindfulness, and control groups. Each intervention was implemented for 6 minutes before the examination. Physiological stress levels were collected during the intervention. Psychological stress levels were rated by students at baseline and after the intervention. Personality traits were assessed via the Big-Five Inventory. Interactions between personality traits and the efficacy of the interventions were analyzed using multivariable linear regression models. RESULTS: Four hundred eighty-one students participated. Higher baseline psychological stress levels were associated with higher neuroticism and agreeableness ( ß = 10.27 [95% confidence interval {CI}, 7.40-13.13; P < .001] and ß = 3.42 [95% CI, 0.98-5.85; P = .006], respectively) and lower openness ( ß = -4.95; 95% CI, -7.40 to -2.49; P < .001). As compared with the control intervention, both stress management interventions led to lower levels of psychological ( P < .001 for both) and physiological stress levels (biofeedback: P < .001 and mindfulness: P = .009). Biofeedback efficacy varied by extraversion score for psychological ( ß = -5.66; 95% CI, -10.83 to -0.50; P = .03) and physiological stress reduction ( ß = -0.002; 95% CI, -0.003 to -0.00004; P = .045). Mindfulness efficacy varied by agreeableness score for psychological stress reduction ( ß = -7.87; 95% CI, -13.05 to -2.68; P = .003). CONCLUSIONS: Students with a high score in extraversion may benefit more from biofeedback interventions, while students with high scores in agreeableness may benefit more from mindfulness interventions.
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Biorretroalimentação Psicológica , Atenção Plena , Personalidade , Estresse Psicológico , Estudantes de Medicina , Humanos , Estudantes de Medicina/psicologia , Estudantes de Medicina/estatística & dados numéricos , Feminino , Masculino , Estresse Psicológico/terapia , Estresse Psicológico/psicologia , Atenção Plena/métodos , Biorretroalimentação Psicológica/métodos , Adulto , Adulto JovemRESUMO
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.
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COVID-19 , Vírus da Influenza A Subtipo H1N1 , Influenza Humana , Infecções por Vírus Respiratório Sincicial , Adulto , Humanos , Estudos Retrospectivos , Unidades de Terapia Intensiva , Vírus Sinciciais RespiratóriosRESUMO
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.
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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.
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Guided biomarker-personalized immunotherapy is advancing rapidly as a means to rejuvenate immune function in injured patients who are the most immunosuppressed. A recent study introduced a fully automated interferon-γ release assay (IGRA) for monitoring the functionality of T lymphocytes in patients with septic shock. While a significant decrease in IFN-γ release capacity was observed, a significant correlation with CD8 lymphocyte absolute count was also reported, raising the question of whether ex-vivo IFN-γ production would be only a surrogate marker for lymphocyte count or if these two parameters conveyed distinct and complementary information. In a large cohort of more than 353 critically ill patients following various injuries (sepsis, trauma, major surgery), the primary objective of the present study was to simultaneously evaluate the association between ex vivo IFN-γ release and CD8 cell count with regard to adverse outcome. Our findings provide a clear-cut result, as they distinctly demonstrate that IGRA offers higher-quality information than CD8 count in terms of an independent association with the occurrence of an adverse outcome. These results strengthen the case for incorporating IGRA into the array of biomarkers of interest for defining endotypes in sepsis. This holds especially true given that fully automated tests are now readily available and could be used in routine clinical practice.
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Testes de Liberação de Interferon-gama , Sepse , Humanos , Testes de Liberação de Interferon-gama/métodos , Interferon gama , Estado Terminal , Terapia de Imunossupressão , Contagem de Linfócitos , Linfócitos T CD8-Positivos , BiomarcadoresRESUMO
The development of new extracorporeal blood purification (EBP) techniques has led to increased application in clinical practice but also inconsistencies in nomenclature and misunderstanding. In November 2022, an international consensus conference was held to establish consensus on the terminology of EBP therapies. It was agreed to define EBP therapies as techniques that use an extracorporeal circuit to remove and/or modulate circulating substances to achieve physiological homeostasis, including support of the function of specific organs and/or detoxification. Specific acute EBP techniques include renal replacement therapy, isolated ultrafiltration, hemoadsorption, and plasma therapies, all of which can be applied in isolation and combination. This paper summarizes the proposed nomenclature of EBP therapies and serves as a framework for clinical practice and future research.
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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.
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Injúria Renal Aguda , Sepse , Humanos , Alta do Paciente , Estresse Financeiro , Tempo de Internação , Hospitais , Injúria Renal Aguda/epidemiologia , Sepse/epidemiologia , Estudos RetrospectivosRESUMO
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.
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Anestesiologia , Treinamento com Simulação de Alta Fidelidade , Humanos , Masculino , Feminino , Estudos Retrospectivos , Simulação por Computador , Anestesiologia/educação , Competência Clínica , Atenção à SaúdeRESUMO
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]â¢[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]â¢[IGFBP7] seems feasible and appears to be safe in patients with sepsis.
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Patients with severe thermal injury require urgent specialized care in burn units. These units assure good coordination of a bundle of care including fluid resuscitation, nutritional support, respiratory care, surgical care and wound care, infection prevention, and rehabilitation. When severely injured, burn patients present a systemic inflammatory response syndrome, associated with a dysregulated immune homeostasis. This complex host response exposes patients to prolonged hospitalization with suppressed immune function, increased susceptibility to secondary infections, longer organ support, and increased mortality. To date, several strategies, such as hemoperfusion techniques, have been developed to mitigate immune activation. We propose herein a review of the immune response to burn injury and the rationale and potential applications of extracorporeal blood purification techniques such as hemoperfusion for burn patients' management.
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Hemoperfusão , Ressuscitação , Humanos , Ressuscitação/métodos , HidrataçãoRESUMO
BACKROUND: The CAST Grid has been developed to evaluate the use of closed-loop communication (CLC) in the trauma bay. METHODS: The CAST Grid and two validated non-technical team performance assessment tools (the TEAM and T-NOTECHS grids) were completed by 2 independent reviewers based on trauma care simulation videos from a French Level 1 trauma center. Intra- and inter-rater agreements were evaluated for CLC parameters and non-technical performance, and correlations between these parameters were analyzed. RESULTS: The study analyzed 11 videos. The intra- and inter-rater agreement for the number of CLC per minute (CLC/min) was moderate and good, respectively, based on Lin's concordance correlation coefficient [95%CI] (0.57 [-0.40;0.94] and 0.77 [0.33;0.94]). However, the agreement was poor for the percentage of CLC (0.37 [-0.58;0.89] and -0.36 [-0.71;0.14], respectively). The study found that a lower number of CLC/min was correlated with an increased duration of the simulation (r = -0.75 [-0.93; -0.25]). CONCLUSION: The CAST Grid showed a relatively good inter-rater agreement to quantify the number of CLC/min which was inversely correlated with the duration of care. This tool opens up the possibility of quantifying CLC and allows for new analyses of team functioning and interactions.