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OBJECTIVE: Ischemic complications account for significant patient morbidity following aneurysmal subarachnoid hemorrhage (aSAH). The Prevention and Treatment of Vasospasm with Clazosentan (REACT) study was designed to assess the safety and efficacy of clazosentan, an endothelin receptor antagonist, in preventing clinical deterioration due to delayed cerebral ischemia (DCI) in patients with aSAH. METHODS: REACT was a prospective, multicenter, randomized, double-blind, phase 3 study. Eligible patients had aSAH secured by surgical clipping or endovascular coiling, and had presented with thick and diffuse clot on admission CT scan. Patients were randomized (1:1 ratio) to 15 mg/hour intravenous clazosentan or placebo within 96 hours of the aSAH for up to 14 days, in addition to standard of care treatment including oral or intravenous nimodipine. The primary efficacy endpoint was the occurrence of clinical deterioration due to DCI up to 14 days after initiation of the study drug. The main secondary endpoint was the occurrence of clinically relevant cerebral infarction at day 16 after study drug initiation. Other secondary endpoints included clinical outcome assessed on the modified Rankin Scale (mRS) and the Glasgow Outcome Scale-Extended (GOSE) at week 12 post-aSAH. Imaging and clinical endpoints were centrally adjudicated. RESULTS: A total of 409 patients were randomized between February 2019 and May 2022 across 74 international sites. Three patients did not start study treatment and were not included in the analysis set. The occurrence of clinical deterioration due to DCI was 15.8% (32/202 patients) in the clazosentan group and 17.2% (35/204 patients) in the placebo group, and the difference was not statistically significant (relative risk reduction [RRR] 7.2%, 95% CI -42.6% to 39.6%, p = 0.734). A nonsignificant RRR of 34.1% (95% CI -21.3% to 64.2%, p = 0.177) was observed in clinically relevant cerebral infarcts treated with clazosentan (7.4%, 15/202) versus placebo (11.3%, 23/204). Rescue therapy was less frequently needed for patients treated with clazosentan compared to placebo (10.4%, 21/202 vs 18.1%, 37/204; RRR 42.6%, 95% CI 5.4%-65.2%). A nonsignificant relative risk increase of 25.4% (95% CI -10.7% to 76.0%, p = 0.198) was reported in the risk of poor GOSE and mRS scores with clazosentan (24.8%, 50/202) versus placebo (20.1%, 41/204) at week 12 post-aSAH. Treatment-emergent adverse events were similar to those reported previously. CONCLUSIONS: Clazosentan administered for up to 14 days at 15 mg/hour had no significant effect on the occurrence of clinical deterioration due to DCI. Clinical trial registration no.: NCT03585270 (ClinicalTrials.gov) EU clinical trial registration no.: 2018-000241-39 (clinicaltrialsregister.eu).
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BACKGROUND: Cardiac injury caused by a sharp object is a medical and surgical therapeutic challenge. Mortality risk factors have been identified but there are major discrepancies in the literature. The aim of this study was to analyse the management of victims of penetrating cardiac injuries before and after admission to hospital and the anatomical characteristics of these injuries in order to facilitate diagnosis of the most critical patients. METHODS: To carry out this study, we conducted a retrospective analytical study with epidemiological data on victims of penetrating cardiac injuries. We included two types of patients, with those who underwent autopsy in our institution after death from sharp injury to the heart or great vessels and those who survived with treatment in the emergency department or intensive care unit between January 2015 and February 2022. RESULTS: We included 30 autopsied patients and 12 survivors aged between 18 and 73 years. Higher mortality was associated with prehospital or in-hospital cardiorespiratory arrest (OR = 4, CI [1.71-9.35]), preoperative mechanical ventilation (OR = 10, CI [1.53-65.41]), preoperative catecholamines (OR = 7, CI [1.12-6.29]), preoperative and perioperative adrenaline (OR = 13, CI [1.98-85.46] and [1.98-85.46]), penetrating cardiac injury (OR = 14, CI [2.10-93.22]), multiple cardiac injuries (OR = 1.5, CI [1.05-2.22]) and an Organ Injury Scaling of the American Association for the Surgery of Trauma (AAST-OIS) score of 5 (OR = 2.9, CI [1.04-8.54]; p = 0.0329) with an AUC-ROC curve value of 0.708 (CI [0.543-0.841]). CONCLUSIONS: This study identified risk mortality factors in penetrating cardiac injury patients. These findings can help improve the diagnosis and management of these patients. The AAST-OIS score may be a good tool to diagnose critical patients.
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Procedimentos Neurocirúrgicos , Assistência Perioperatória , Tromboembolia Venosa , Humanos , Tromboembolia Venosa/prevenção & controle , Tromboembolia Venosa/etiologia , Assistência Perioperatória/métodos , Assistência Perioperatória/normas , Procedimentos Neurocirúrgicos/normas , Procedimentos Neurocirúrgicos/efeitos adversos , Europa (Continente) , Anticoagulantes/administração & dosagem , Complicações Pós-Operatórias/prevenção & controle , Complicações Pós-Operatórias/etiologiaAssuntos
Assistência Perioperatória , Tromboembolia Venosa , Ferimentos e Lesões , Humanos , Tromboembolia Venosa/prevenção & controle , Tromboembolia Venosa/etiologia , Assistência Perioperatória/métodos , Assistência Perioperatória/normas , Ferimentos e Lesões/complicações , Europa (Continente) , Anticoagulantes/administração & dosagem , Anticoagulantes/efeitos adversos , Complicações Pós-Operatórias/prevenção & controle , Complicações Pós-Operatórias/etiologiaRESUMO
BACKGROUND/OBJECTIVES: Aneurysmal subarachnoid haemorrhage (aSAH) is a life-threatening event with major complications. Delayed cerebral infarct (DCI) occurs most frequently 7 days after aSAH and can last for a prolonged period. To determine the most predictive radiological scales in grading subarachnoid or ventricular haemorrhage or both for functional outcome at 3 months in a large aSAH population, we conducted a single-centre retrospective study. METHODS: A 3-year single-centre retrospective cohort study of 230 patients hospitalised for aSAH was analysed. Initial computed tomography (CT) scans in patients hospitalised for aSAH were blindly assessed using eight grading systems: the Fisher grade, modified Fisher grade, Barrow Neurological Institute scale, Hijdra scale, Intraventricular Haemorrhage (IVH) score, Graeb score and LeRoux score. RESULTS: Of 200 patients with aSAH who survived to day 7 and were included for DCI analysis, 39% of cases were complicated with DCI. The Hijdra scale was the best predictor for DCI, with a receiver operating characteristic area under the curve (ROCAUC) of 0.80 (95% confidence interval (CI), 0.74-0.85). The IVH score was the most effective grading system for predicting acute hydrocephalus, with a ROCAUC of 0.85 (95% CI, 0.79-0.89). In multivariate analysis, the Hijdra scale was the best predictor of the occurrence of DCI (hazard ratio, 1.18; 95% CI, 1.10-1.25). CONCLUSIONS: Although these results have yet to be prospectively confirmed, our findings suggest that the Hijdra scale may be a good predictor of DCI and could be useful in daily clinical practice. CLINICAL RELEVANCE STATEMENT: Better assessment of subarachnoid haemorrhage patients would allow for better prognostication and management of expectations, as well as referral for appropriate services and helping to appropriate use limited critical care resources. KEY POINTS: Aneurysmal subarachnoid haemorrhage is a life-threatening event that causes severe disability and leads to major complications such as delayed cerebral infarction. Accurate assessment of the amount of blood in the subarachnoid spaces on computed tomography with the Hijdra scale can better predict the risk of delayed cerebral infarct. The Hijdra scale could be a good triage tool for subarachnoid haemorrhage patients.
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Introduction: During COVID-19, renal impairment is associated with poor prognosis in intensive care unit (ICU). We aimed to assess the existence and incidence of early renal dysfunction and its prognostic value in patients with COVID-19-related acute respiratory distress syndrome (ARDS). Methods: In this prospective multicenter study, patients aged over 18 years with invasive mechanical ventilation (MV) for ARDS were enrolled in 3 ICUs. Precise evaluation of renal dysfunction markers, including urinary protein electrophoresis (UPE) and quantification, was performed within 24 hours after MV onset. Results: From March 2020 to December 2021, 135 patients were enrolled as follows: 100 with COVID-19 ARDS and 35 with non-COVID-19 ARDS. UPE found more tubular dysfunction in patients with COVID-19 (68% vs. 21.4%, P < 0.0001) and more normal profiles in patients without COVID-19 (65.0% vs. 11.2%, P = 0.0003). Patients with COVID-19 significantly displayed early urinary leakage of tubular proteins such as beta-2-microglobulin (ß2m) and free light chains, tended to display acute kidney injury (AKI) more frequently (51.0% vs. 34.3%, P = 0.088), had longer MV (20 vs. 9 days, P < 0.0001) and longer ICU stay (26 vs. 15 days, P < 0.0001). In COVID-19 ARDS, leakage of free lambda light chain was associated with the onset of Kidney Disease: Improving Global Outcomes (KDIGO) ≥2 AKI (odds ratio [OR]: 1.014, 95% confidence interval [CI] 1.003-1.025, P = 0.011). Conclusion: Patients with COVID-19-related ARDS display a proximal tubular dysfunction before the onset of AKI, which predicts AKI. Proximal tubular damage seems an important mechanism of COVID-19-induced nephropathy. Analysis of urinary proteins is a reliable noninvasive tool to assess proximal tubular dysfunction in the ICU.
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Delírio , Delírio do Despertar , Humanos , Delírio/diagnóstico , Delírio/etiologia , Delírio/prevenção & controle , Delírio do Despertar/diagnóstico , Delírio do Despertar/epidemiologia , Delírio do Despertar/etiologia , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/prevenção & controle , Guias de Prática Clínica como AssuntoRESUMO
BACKGROUND: In intensive care units (ICUs), accurate mortality prediction is crucial for effective patient management and resource allocation. The Simplified Acute Physiology Score II (SAPS-2), though commonly used, relies heavily on comprehensive clinical data and blood samples. This study sought to develop an artificial intelligence (AI) model utilizing key hemodynamic parameters to predict ICU mortality within the first 24 h and assess its performance relative to SAPS-2. METHODS: We conducted an analysis of select hemodynamic parameters and the structure of heart rate curves to identify potential predictors of ICU mortality. A machine-learning model was subsequently trained and validated on distinct patient cohorts. The AI algorithm's performance was then compared to the SAPS-2, focusing on classification accuracy, calibration, and generalizability. MEASUREMENTS AND MAIN RESULTS: The study included 1298 ICU admissions from March 27th, 2015, to March 27th, 2017. An additional cohort from 2022 to 2023 comprised 590 patients, resulting in a total dataset of 1888 patients. The observed mortality rate stood at 24.0%. Key determinants of mortality were the Glasgow Coma Scale score, heart rate complexity, patient age, duration of diastolic blood pressure below 50 mmHg, heart rate variability, and specific mean and systolic blood pressure thresholds. The AI model, informed by these determinants, exhibited a performance profile in predicting mortality that was comparable, if not superior, to the SAPS-2. CONCLUSIONS: The AI model, which integrates heart rate and blood pressure curve analyses with basic clinical parameters, provides a methodological approach to predict in-hospital mortality in ICU patients. This model offers an alternative to existing tools that depend on extensive clinical data and laboratory inputs. Its potential integration into ICU monitoring systems may facilitate more streamlined mortality prediction processes.
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Inteligência Artificial , Unidades de Terapia Intensiva , Humanos , Projetos Piloto , Frequência Cardíaca , Mortalidade Hospitalar , Curva ROCRESUMO
This study aimed to develop a Monte Carlo simulation model to forecast the number of ICU beds needed for COVID-19 patients and the subsequent nursing complexity in a French teaching hospital during the first and second pandemic outbreaks. The model used patient data from March 2020 to September 2021, including age, sex, ICU length of stay, and number of patients on mechanical ventilation or extracorporeal membrane oxygenation. Nursing complexity was assessed using a simple scale with three levels based on patient status. The simulation was performed 1000 times to generate a scenario, and the mean outcome was compared with the observed outcome. The model also allowed for a 7-day forecast of ICU occupancy. The simulation output had a good fit with the actual data, with an R2 of 0.998 and a root mean square error of 0.22. The study demonstrated the usefulness of the Monte Carlo simulation model for predicting the demand for ICU beds and could help optimize resource allocation during a pandemic. The model's extrinsic validity was confirmed using open data from the French Public Health Authority. This study provides a valuable tool for healthcare systems to anticipate and manage surges in ICU demand during pandemics.
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COVID-19 , Unidades de Terapia Intensiva , Método de Monte Carlo , Humanos , COVID-19/epidemiologia , França/epidemiologia , Feminino , Masculino , Pandemias , Pessoa de Meia-Idade , SARS-CoV-2 , Adulto , Idoso , PrevisõesRESUMO
Delayed cerebral ischemia (DCI) following aneurysmal subarachnoid hemorrhage (aSAH) is a major cause of complications and death. Here, we set out to identify high-performance predictive biomarkers of DCI and its underlying metabolic disruptions using metabolomics and lipidomics approaches. This single-center prospective observational study enrolled 61 consecutive patients with severe aSAH; among them, 22 experienced a DCI. Nine patients without aSAH were included as validation controls. Blood and cerebrospinal fluid (CSF) were sampled within the first 24 h after admission. We identified a panel of 20 metabolites that, together, showed high predictive performance for DCI. This panel of metabolites included lactate, cotinine, salicylate, 6 phosphatidylcholines, and 4 sphingomyelins. The interplay of the metabolome and the lipidome found between CSF and plasma in our patients underscores that aSAH and its associated DCI complications can extend beyond cerebral implications, with a peripheral dimension as well. As an illustration, early biological disruptions that might explain the subsequent DCI found systemic hypoxia driven mainly by higher blood lactate, arginine, and proline metabolism likely associated with vascular NO and disrupted ceramide/sphingolipid metabolism. We conclude that targeting early peripheral hypoxia preceding DCI could provide an interesting strategy for the prevention of vascular dysfunction.
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Isquemia Encefálica , Hemorragia Subaracnóidea , Humanos , Hemorragia Subaracnóidea/complicações , Isquemia Encefálica/etiologia , Biomarcadores , Ácido Láctico , HipóxiaRESUMO
BACKGROUND: The aims of this study were to describe pharmacokinetic/pharmacodynamic target attainment in intensive care unit (ICU) patients treated with continuously infused ß-lactam antibiotics, their associated covariates, and the impact of dosage adjustment. METHODS: This prospective, observational, cohort study was performed in three ICUs. Four ß-lactams were continuously infused, and therapeutic drug monitoring (TDM) was performed at days 1, 4, and 7. The primary pharmacokinetic/pharmacodynamic target was an unbound ß-lactam plasma concentration four times above the bacteria's minimal inhibitory concentration during the whole dosing interval. The demographic and clinical covariates associated with target attainment were evaluated. RESULTS: A total of 170 patients were included (426 blood samples). The percentages of empirical ß-lactam underdosing at D1 were 66% for cefepime, 43% for cefotaxime, 47% for ceftazidime, and 14% for meropenem. Indexed creatinine clearance was independently associated with treatment underdose if increased (adjusted odds ratio per unit, 1.01; 95% CI, 1.00 to 1.01; p = 0.014) or overdose if decreased (adjusted odds ratio per unit, 0.95; 95% CI, 0.94 to 0.97; p < 0.001). Pharmacokinetic/pharmacodynamic target attainment was significantly increased after ß-lactam dosage adjustment between day 1 and day 4 vs. no adjustment (53.1% vs. 26.2%; p = 0.018). CONCLUSIONS: This study increases our knowledge on the optimization of ß-lactam therapy in ICU patients. A large inter- and intra-patient variability in plasmatic concentrations was observed, leading to inadequate exposure. A combined indexed creatinine clearance and TDM approach enables adequate dosing for better pharmacokinetic/pharmacodynamic target attainment.
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The emission spectrum of a dye is given by the energy of all of the possible radiative transitions weighted by their probability. This spectrum can be altered with optical nanoantennas that are able to manipulate the decay rate of nearby emitters by modifying the local density of photonic states. Here, we make use of DNA origami to precisely place an individual dye at different positions around a gold nanorod and show how this affects the emission spectrum of the dye. In particular, we observe a strong suppression or enhancement of the transitions to different vibrational levels of the excitonic ground state, depending on the spectral overlap with the nanorod resonance. This reshaping can be used to experimentally extract the spectral dependence of the radiative decay rate enhancement. Furthermore, for some cases, we argue that the drastic alteration of the fluorescence spectrum could arise from the violation of Kasha's rule.
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BACKGROUND: Burnout syndrome (BOS) impacts health workers and has become a real public health issue. The primary objective of this observational study was to re-evaluate the incidence of BOS among anesthesiologists and intensivists (AI) in France, ten years after the SESMAT study, a French Physician Health Survey carried out among burnout salaried AI. The secondary objective was to investigate risks factors. METHODS: The REPAR survey is an observational study carried in France among AI, residents, and seniors, whatever their main mode of practice, in the framework of a self-questionnaire distributed on the Internet from 11 April 2018 to 1 July 2018. BOS was assessed using the Copenhagen Burnout Inventory (CBI). A score above 50% on two of the dimensions (personal burnout and work-related burnout) indicated BOS, as a main criterion. In order to investigate risks factors, questions were about sociodemographic characteristics, professional and extraprofessional environments, personality and mood using the Major Depression Inventory (MDI). A significance threshold of p < 0.05 was retained. RESULTS: Among 1519 questionnaires received, 1500 completed questionnaires were analyzed. There were 775 men (52%) and 721 women (48%), aged 23 to 74 years. Among those, 24% suffered from BOS, 9% showed depressive symptoms (MDI > 25) and 35% were considering changing jobs or stopping their studies. There was no significant difference with the SESMAT study for the general BOS score. After multivariate analysis, 12 variables were significantly associated with the main criterion. CONCLUSIONS: Ten years after the SESMAT study, the incidence of BOS in AI has not decreased in the largest cohort of AI studied to date in France.
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Esgotamento Profissional , Médicos , Masculino , Humanos , Feminino , Anestesiologistas , Incidência , Esgotamento Profissional/epidemiologia , Inquéritos e Questionários , França/epidemiologiaRESUMO
The benefits of decompressive craniectomy (DC) have been demonstrated in malignant ischemic stroke and traumatic brain injuries with refractory intracranial hypertension (ICH) by randomized controlled trials. Some reports advocate the potential of DC in the context of ICH due to meningoencephalitis (ME) with focal cerebral edema, but its interest remains controversial especially when there is diffuse cerebral edema. The aim of this study is to assess the benefits of DC in meningoencephalitis with malignant cerebral edema whether it is focal or diffuse. We report two cases successfully treated in our institute, plus we conducted a systematic literature review focused on cases of DC in ME in compliance with Prisma guidelines. The first patient is a 36-year-old woman who suffered from fulminant pneumococcal meningoencephalitis (ME) with refractory ICH following a transsphenoidal removal of pituitary adenoma. The second patient is a 20-year-old man suffering from neuro-meningeal cryptococcosis with refractory ICH. In both cases DC led to major clinical improvement with a GOS-E 8 at one year. These results are consistent with the literature review which reports a favorable outcome in 85% of cases. DC appears to be a promising therapeutic option in cases of ME with refractory ICH. Thus, reliable criteria will have to be defined to guide us in our practice in emergency cases where DC has not been part of the therapeutic arsenal yet.
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Edema Encefálico , Lesões Encefálicas Traumáticas , Craniectomia Descompressiva , Hipertensão Intracraniana , Meningoencefalite , Masculino , Feminino , Humanos , Adulto , Adulto Jovem , Craniectomia Descompressiva/métodos , Edema Encefálico/cirurgia , Hipertensão Intracraniana/etiologia , Hipertensão Intracraniana/cirurgia , Lesões Encefálicas Traumáticas/cirurgia , Resultado do TratamentoRESUMO
BACKGROUND: For patients presenting with an aneurysmal subarachnoid hemorrhage (aSAH), delayed cerebral ischemia (DCI) is a significant cause of morbidity and mortality. The REACT study is designed to assess the safety and efficacy of clazosentan in preventing clinical deterioration due to DCI in patients with aSAH. METHODS: REACT is a prospective, multicenter, randomized phase 3 study that is planned to enroll 400 patients with documented aSAH from a ruptured cerebral aneurysm, randomized 1:1 to 15 mg/hour intravenous clazosentan vs. placebo, in approximately 100 sites and 15 countries. Eligible patients are required to present at hospital admission with CT evidence of significant subarachnoid blood, defined as a thick and diffuse clot that is more than 4 mm in thickness and involves 3 or more basal cisterns. The primary efficacy endpoint is the occurrence of clinical deterioration due to DCI up to 14 days post-study drug initiation. The main secondary endpoint is the occurrence of clinically relevant cerebral infarction at Day 16 post-study drug initiation. Other secondary endpoints include the modified Rankin Scale (mRS) and the Glasgow Outcome Scale-Extended (GOSE) score at Week 12 post-aSAH, dichotomized into poor and good outcome. Radiological results and clinical endpoints are centrally evaluated by independent committees, blinded to treatment allocation. Exploratory efficacy endpoints comprise the assessment of cognition status at 12 weeks and quality of life at 12 and 24 weeks post aSAH. DISCUSSION: In the REACT study, clazosentan is evaluated on top of standard of care to determine if it reduces the risk of clinical deterioration due to DCI after aSAH. The selection of patients with thick and diffuse clots is intended to assess the benefit/risk profile of clazosentan in a population at high risk of vasospasm-related ischemic complications post-aSAH. TRIAL REGISTRATION (ADDITIONAL FILE 1): ClinicalTrials.gov (NCT03585270). EU Clinical Trial Register (EudraCT Number: 2018-000241-39).