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Brief abstract: In a multicentre network of 28 ICUs in France and Belgium, all comatose patients who fulfilled the 2021 ERC-ESICM criteria for poor outcome after cardiac arrest died or survived with severe neurological disability, even after excluding patients with active WLST to limit self-fulfilling prophecy bias. However, in almost half of the patients, these criteria were not fulfilled, resulting in an indeterminate outcome; in these patients, normal NSE levels and benign EEG predicted neurological recovery, helping reduce prognostic uncertainty. AIM: To investigate the performance of the 2021 ERC/ESICM-recommended algorithm for predicting poor outcome after cardiac arrest (CA) and potential tools for predicting neurological recovery in patients with indeterminate outcome. METHODS: Prospective, multicenter study on out-of-hospital CA survivors from 28 ICUs of the AfterROSC network. In patients comatose with a Glasgow Coma Scale motor score ≤3 at ≥72 hours after resuscitation, we measured: 1) the accuracy of neurological examination, biomarkers (neuron-specific enolase, NSE), electrophysiology (EEG and SSEP) and neuroimaging (brain CT and MRI) for predicting poor outcome (modified Rankin scale score≥4 at 90 days), and 2) the ability of low or decreasing NSE levels and benign EEG to predict good outcome in patients whose prognosis remained indeterminate. RESULTS: Among 337 included patients, the ERC-ESICM algorithm predicted poor neurological outcome in 175 patients, of whom 106 (60%) had withdrawal of life-sustaining treatment (WLST). Among the 69 patients without active WLST, the positive predictive value for an unfavourable outcome was 100% [95-100]%. The specificity of individual predictors ranged from 90% for EEG to 100% for clinical examination and SSEP. Among the remaining 162 patients with indeterminate outcome, a combination of 2 favourable signs predicted good outcome with 99[96-100]% specificity and 23[11-38%]% sensitivity. Conclusion All comatose resuscitated patients not undergoing WLST who fulfilled the ERC-ESICM criteria for poor outcome after CA had poor outcome at three months, even if a self-fulfilling prophecy cannot be completely excluded. In patients with indeterminate outcome (half of the population), favourable signs predicted neurological recovery, reducing prognostic uncertainty.
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BACKGROUND: The first aim of this study was to evaluate the capacity of electrical impedance tomography (EIT) to identify the effect of PEEP on regional ventilation distribution and the regional risk of collapse, overdistention, hypoventilation, and pendelluft in mechanically ventilated patients. The second aim was to evaluate the feasibility of EIT for estimating airway opening pressure (AOP). METHODS: The EIT signal was recorded both during baseline cyclic ventilation and slow insufflation for one breath for 9 subjects with moderate-to-severe ARDS. From these data, the AOP and volumes insufflated to lung regions with or without the risk of either collapse, overdistention, hypoventilation, or pendelluft were assessed at 3 PEEP levels (5, 10, and 15 cm H2O). PEEP levels were compared by Friedman analysis of variance and the AOP measured by EIT evaluated using an F-test and the Bland and Altman method. RESULTS: The volume for which there was no specific risk significantly decreased at the highest PEEP from 55 ± 31% tidal volume (VT) at PEEP 5 or 82 ± 18% VT at PEEP 10 to 10 ± 30% VT at PEEP 15 (P = .038 between PEEP 5 vs PEEP 15; P = .01 between PEEP 10 vs PEEP 15). The volume associated with overdistention significantly increased with increasing PEEP, whereas that associated with atelectrauma significantly decreased. Pendelluft significantly decreased with increasing PEEP: VT of 8.9 ± 18.6%, 3.6 ± 7.0%, and 3.2 ± 7.1% for PEEP 5, PEEP 10, and PEEP 15, respectively. The center of ventilation tended to increase in the dependent direction with higher PEEP. The AOPs assessed by EIT and from the pressure-volume curve were in good agreement (bias 0.48 cm H2O). CONCLUSIONS: Our results suggest that EIT could aid clinicians in making personalized and reasoned choices in setting the PEEP for subjects with ARDS.
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BACKGROUND: Bradycardia and dysautonomia observed during SARS-Cov2 infection suggests involvement of the autonomic nervous system (ANS). Limited data exists on ANS dysregulation and its association with outcomes in patients with acute respiratory distress syndrome (ARDS) related to COVID-19 (C-ARDS) or other etiologies (NC-ARDS). OBJECTIVES: We aimed to explore sympathovagal balance, assessed by heart rate variability (HRV), and its clinical prognostic value in C-ARDS compared with NC-ARDS. METHODS: A single-center, prospective case-control study was conducted. Consecutive patients meeting ARDS criteria between 2020 and 2022 were included. HRV was assessed using 1-hour electrographic tracing during a stable, daytime period. RESULTS: Twenty-four patients with C-ARDS and 19 with NC-ARDS were included. Age, sex and ARDS severity were similar between groups. The median heart rate was markedly lower in the C-ARDS group than in the NC-ARDS group (60 [53-72] versus 101 [91-112] bpm, p<.001). Most of HRV parameters were significantly increased in patients with C-ARDS. HRV correlated with heart rate only in patients with C-ARDS. A positive correlation was found between the low-to high-frequency ratio (LF/HF) and length of intensive care unit stay (r = 0.576, p<.001). CONCLUSION: This study confirmed that C-ARDS was associated with marked bradycardia and severe ANS impairment, suggesting a sympathovagal imbalance with vagal overtone. Poor outcomes appeared to be more related to sympathetic rather than parasympathetic hyperactivation.
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PURPOSE: Coronary artery bypass grafting (CABG) on cardiopulmonary bypass (CPB) is associated with myocardial ischemia-reperfusion injury (IRI), which may limit the benefit of the surgery. Both experimental and clinical studies suggest that Intralipid, a lipid emulsion commonly used for parenteral nutrition, can limit myocardial IRI. We therefore aimed to investigate whether Intralipid administered at reperfusion can reduce myocardial IRI in patients undergoing CABG on CPB. METHODS: We conducted a randomized, double-blind, pilot trial in which 29 adult patients scheduled for CABG were randomly assigned (on a 1:1 basis) to receive either 1.5 ml/kg Intralipid 20% or Ringer's Lactate 3 min before aortic cross unclamping. The primary endpoint was the 72-h area under the curve (AUC) for troponin I. RESULTS: Of the 29 patients randomized, 26 were included in the study (two withdrew consent and one was excluded before surgery). The 72-h AUC for troponin I did not significantly differ between the control and Intralipid group (546437 ± 205518 versus 487561 ± 115724 arbitrary units, respectively; P = 0.804). Other outcomes (including 72-h AUC for CK-MB, C-reactive protein, need for defibrillation, time to extubation, length of ICU and hospital stay, and serious adverse events) were similar between the two groups. CONCLUSION: In patients undergoing CABG on CPB, Intralipid did not limit myocardial IRI compared to placebo. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02807727 (registration date: 16 June 2016).
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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 , Monocitos , Humanos , COVID-19/mortalidad , COVID-19/inmunología , Masculino , Femenino , Monocitos/metabolismo , Monocitos/inmunología , Persona de Mediana Edad , Anciano , Unidades de Cuidados Intensivos , SARS-CoV-2 , Biomarcadores/sangre , Índice de Severidad de la EnfermedadRESUMEN
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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BACKGROUND: Invasive candidiasis is still recognized as a major cause of morbidity and mortality. To support clinicians in the optimal use of antifungals for the treatment of invasive candidiasis, a computerized decision support system (CDSS) was developed based on institutional guidelines. OBJECTIVES: To evaluate the correlation of this newly developed CDSS with clinical practices, we set-up a retrospective multicentre cohort study with the aim of providing the concordance rate between the CDSS recommendation and the medical prescription (NCT05656157). PATIENTS AND METHODS: Adult patients who received caspofungin or fluconazole for the treatment of an invasive candidiasis were included. The analysis of factors associated with concordance was performed using mixed logistic regression models with department as a random effect. RESULTS: From March to November 2022, 190 patients were included from three centres and eight departments: 70 patients from centre A, 84 from centre B and 36 from centre C. Overall, 100 patients received caspofungin and 90 received fluconazole, mostly (59%; 112/190) for empirical/pre-emptive treatment. The overall percentage of concordance between the CDSS and medical prescriptions was 91% (173/190) (confidence interval 95%: 82%-96%). No significant difference in concordance was observed considering the centres (Pâ>â0.99), the department of inclusion (Pâ=â0.968), the antifungal treatment (Pâ=â0.656) or the indication of treatment (Pâ=â0.997). In most cases of discordance (nâ=â13/17, 76%), the CDSS recommended fluconazole whereas caspofungin was prescribed. The clinical usability evaluated by five clinicians was satisfactory. CONCLUSIONS: Our results demonstrated the high correlation between current antifungal clinical practice and this user-friendly and institutional guidelines-based CDSS.
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Antifúngicos , Candidiasis Invasiva , Caspofungina , Sistemas de Apoyo a Decisiones Clínicas , Fluconazol , Humanos , Estudios Retrospectivos , Antifúngicos/uso terapéutico , Antifúngicos/administración & dosificación , Masculino , Femenino , Persona de Mediana Edad , Fluconazol/uso terapéutico , Fluconazol/administración & dosificación , Anciano , Candidiasis Invasiva/tratamiento farmacológico , Caspofungina/uso terapéutico , Caspofungina/administración & dosificación , Adulto , Anciano de 80 o más Años , Pautas de la Práctica en Medicina/estadística & datos numéricosRESUMEN
RATIONALE: Apart from hypoxic hepatitis (HH), the hepatic consequences of out-of-hospital cardiac arrest (OHCA) have been little studied. This cohort study aimed to investigate the characteristics of liver dysfunction resulting from OHCA and its association with outcomes. METHODS: Among the conventional static liver function tests used to define acute liver failure (ALF), we determined which one correlated more closely with the reference indocyanine green (ICG) clearance test in a series of OHCA patients from the CYRUS trial (NCT01595958). Subsequently, we assessed whether ALF, in addition to HH (i.e., acute liver injury), was an independent risk factor for death in a large cohort of OHCA patients admitted to two intensive care units between 2007 and 2017. RESULTS: ICG clearance, available for 22 patients, was impaired in 17 (77.3%) cases. Prothrombin time (PT) ratio was the only static liver function test that correlated significantly (r = -0.66, p < 0.01) with ICG clearance and was therefore used to define ALF, with the usual cutoff of < 50%. Of the 418 patients included in the analysis (sex ratio: 1.4; median age: 64 [53-75] years; non-shockable rhythm: 73%), 67 (16.0%) presented with ALF, and 61 (14.6%) had HH at admission. On day 28, 337 (80.6%) patients died. Following multivariate analysis, ALF at admission, OHCA occurring at home, absence of bystander, non-cardiac cause of OHCA, low-flow duration ≥ 20 min, and SOFA score excluding liver subscore at admission were independently associated with day 28 mortality. CONCLUSIONS: ALF occurred frequently after OHCA and, unlike HH, was independently associated with day 28 mortality.
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Reanimación Cardiopulmonar , Hepatitis , Fallo Hepático Agudo , Paro Cardíaco Extrahospitalario , Humanos , Persona de Mediana Edad , Paro Cardíaco Extrahospitalario/terapia , Paro Cardíaco Extrahospitalario/complicaciones , Estudios de Cohortes , Fallo Hepático Agudo/complicaciones , Hepatitis/complicacionesRESUMEN
BACKGROUND: Inhaled sedation during invasive mechanical ventilation in patients with acute respiratory distress syndrome (ARDS) has received increasing attention. However, inhaled sedation devices increase dead-space ventilation and an undesirable effect is the increase in minute ventilation needed to maintain CO2 removal. A consequence of raising minute ventilation is an increase in mechanical power (MP) that can promote lung injury. However, the effect of inhaled sedation devices on MP remains unknown. METHODS: We conducted a bench study to assess and compare the effects of three devices delivering inhaled sevoflurane currently available in ICU (AnaConDa-50 mL (ANA-50), AnaConDa-100 mL (ANA-100), and MIRUS) on MP by using a test lung model set with three compliances (20, 40, and 60 mL/cmH2O). We simulated lung-protective ventilation using a low tidal volume and two levels of positive end-expiratory pressure (5 and 15 cmH2O) under ambient temperature and dry conditions. Following the insertion of the devices, either the respiratory rate or tidal volume was increased in 15%-steps until end-tidal CO2 (EtCO2) returned to the baseline value. MP was calculated at baseline and after EtCO2 correction using a simplified equation. RESULTS: Following device insertion, the EtCO2 increase was significantly greater with MIRUS (+ 78 ± 13%) and ANA-100 (+ 100 ± 11%) than with ANA-50 (+ 49 ± 7%). After normalizing EtCO2 by adjusting minute ventilation, MP significantly increased by more than 50% with all inhaled sedation devices compared to controls. The lowest increase in MP was observed with ANA-50 (p < 0.05 versus ANA-100 and MIRUS). The Costa index, another parameter assessing the mechanical energy delivered to the lungs, calculated as driving pressure × 4 + respiratory rate, significantly increased by more than 20% in all experimental conditions. Additional experiments performed under body temperature, ambient pressure, and gas saturated with water vapor conditions, confirmed the main results with an increase in MP > 50% with all devices after normalizing EtCO2 by adjusting minute ventilation. CONCLUSION: Inhaled sedation devices substantially increased MP in this bench model of protective ventilation, which might limit their benefits in ARDS.
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OBJECTIVE: Unplanned invasive mechanical ventilation (IMV) is associated with high mortality in lung cancer patients. We aimed to identify factors associated with weaning from IMV, intensive care unit (ICU) survival and 1-year survival in lung cancer patients requiring unplanned IMV. DESIGN: Retrospective observational study (2007-2017). SETTING: University-affiliated ICU. PATIENTS: Lung cancer patients requiring unplanned IMV. INTERVENTION: None. MAIN VARIABLES OF INTEREST: Weaning from IMV, ICU and 1-year survival. RESULTS: Of the 136 patients included in the analysis (age 64 (9) years, male 110 (81%), metastatic disease 97 (62%)), 52 (38%) were weaned from IMV, 51 (38%) were discharged from ICU and 22 (16%) were alive at 1year. The main indication for intubation was acute respiratory failure. In multivariate analysis, PaO2/FiO2 >175mmHg at ICU admission and intubation before ICU admission were associated with successful weaning from IMV while intubation for cardiac arrest was associated with weaning failure. Same factors were associated with ICU survival. Absence of metastasis at ICU admission and lung resection surgery were independently associated with 1-year survival. CONCLUSIONS: A significant proportion of patients with lung cancer treated with unplanned IMV could be weaned from IMV and survived to ICU discharge, especially in the absence of severe hypoxemia at ICU admission. The low one-year survival was mostly driven by metastatic status.
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Neoplasias Pulmonares , Respiración Artificial , Humanos , Masculino , Persona de Mediana Edad , Neoplasias Pulmonares/terapia , Hospitalización , Unidades de Cuidados Intensivos , Alta del PacienteRESUMEN
Sepsis triggers a complex response marked by the simultaneous presence of proinflammatory and immunosuppressive elements, disrupting the mechanisms intended to maintain homeostasis. While the NLRP3 inflammasome has been demonstrated to contribute to the inflammatory side, its connection with delayed sepsis-induced immunosuppression remains unexplored. The present objective was to concomitantly and prospectively assess NLRP3 activation (IL-1ß, IL-18, and soluble receptors) and features of immune failure (IL-10, mHLA-DR, myeloid-derived suppressor cells) in septic patients. To validate our findings, we conducted a transcriptomic analysis of mRNA of NLRP3-related genes (IL-18R1, IL-1R2) on an additional cohort of 107 patients. Two distinct endotypes were identified. One cluster displayed moderate inflammation rapidly returning to normal values, while the other exhibited a higher inflammatory response persisting until day 28, which was associated with persistent marked immunosuppression and higher 28-d mortality. Identifying endotypes with different pro/anti-inflammatory trajectories could hold important clinical implications for the management of sepsis.
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Inflamasomas , Sepsis , Humanos , Terapia de Inmunosupresión , Inflamasomas/genética , Interleucina-1beta/genética , Proteína con Dominio Pirina 3 de la Familia NLR/genética , Sepsis/genéticaRESUMEN
Sepsis is a life-threatening organ dysfunction caused by a dysregulated response to infection. In this context, the aberrant activation of the NLRP3 inflammasome has been documented mostly through the measurement of increased plasmatic concentrations of IL-1ß and IL-18. At the cellular level, contradictory results have been published. However, no study has comprehensively monitored NLRP3 inflammasome activation at the basal level and after ex vivo reactivation of whole blood monocytes and neutrophils focusing on ICU patients with bacterial and viral sepsis, including a longitudinal analysis. Thus, we conducted a prospective longitudinal study, examining NLRP3 inflammasome functionality in COVID-19 ICU patients (n = 15) and bacterial septic shock patients (n = 17) during the first week of ICU hospitalization, compared with healthy donors. Using two whole-blood flow cytometry assays, we detected ASC speck-positive monocytes (i.e., monocytes presenting the polymerization of ASC proteins) and activated caspase-1 in polymorphonuclear cells as read-outs, both at baseline and following nigericin stimulation, a drug that forms pores and activates the NLRP3 inflammasome. Our findings showed that, at baseline and regardless of the type of infection, patients exhibited reduced ASC speck-positive monocytes and decreased activated caspase-1 in PMN compared to healthy volunteers. This decrease was prominent at day 0. Following nigericin stimulation, this reduction was also observed and persisted throughout the first week of hospitalization, irrespective of the cellular population or parameter being considered. Notably, at day 0, this diminished activation and response to stimulation of NLRP3 was associated with a higher 28-day mortality rate. Consequently, our observations highlighted a concurrent decline in both basal expression and ex vivo activation of the NLRP3 inflammasome in circulating myeloid cells from patients with bacterial and viral sepsis in association with increased mortality.
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Inflamasomas , Sepsis , Humanos , Caspasa 1/metabolismo , Inflamasomas/metabolismo , Estudios Longitudinales , Nigericina , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Estudios Prospectivos , Sepsis/mortalidadRESUMEN
BACKGROUND: Out-of-hospital cardiac arrest (OHCA) is a heterogeneous entity with multiple origins and prognoses. An early, reliable assessment of the prognosis is useful to adapt therapeutic strategy, tailor intensity of care, and inform relatives. We aimed primarily to undertake a prospective multicentric study to evaluate predictive performance of the Cardiac Arrest Prognosis (CAHP) Score as compare to historical dataset systematically collected after OHCA (Utstein style criteria). Our secondary aim was to evaluate other dedicated scores for predicting outcome after OHCA and to compare them to Utstein style criteria. METHODS: We prospectively collected data from 24 French and Belgium Intensive Care Units (ICUs) between August 2020 and June 2022. All cases of non-traumatic OHCA (cardiac and non-cardiac causes) patients with stable return of spontaneous circulation (ROSC) and comatose at ICU admission (defined by Glasgow coma score ≤ 8) on ICU admission were included. The primary outcome was the modified Rankin scale (mRS) at day 90 after cardiac arrest, assessed by phone interviews. A wide range of developed scores (CAHP, OHCA, CREST, C-Graph, TTM, CAST, NULL-PLEASE, and MIRACLE2) were included, and their accuracies in predicting poor outcome at 90 days after OHCA (defined as mRS ≥ 4) were determined using the area under the receiving operating characteristic curve (AUROC) and the calibration belt. RESULTS: During the study period, 907 patients were screened, and 658 were included in the study. Patients were predominantly male (72%), with a mean age of 61 ± 15, most having collapsed from a supposed cardiac cause (64%). The mortality rate at day 90 was 63% and unfavorable neurological outcomes were observed in 66%. The performance (AUROC) of Utstein criteria for poor outcome prediction was moderate at 0.79 [0.76-0.83], whereas AUROCs from other scores varied from 0.79 [0.75-0.83] to 0.88 [0.86-0.91]. For each score, the proportion of patients for whom individual values could not be calculated varied from 1.4% to 17.4%. CONCLUSIONS: In patients admitted to ICUs after a successfully resuscitated OHCA, most of the scores available for the evaluation of the subsequent prognosis are more efficient than the usual Utstein criteria but calibration is unacceptable for some of them. Our results show that some scores (CAHP, sCAHP, mCAHP, OHCA, rCAST) have superior performance, and that their ease and speed of determination should encourage their use. Trial registration https://clinicaltrials.gov/ct2/show/NCT04167891.
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PURPOSE: This study aimed to assess the outcome and factors associated with mortality in patients who received urgent chemotherapy (CT) in the intensive care unit (ICU) in Lyon, France. MATERIAL AND METHODS: A total of 147 adult patients diagnosed with cancer and requiring urgent CT during ICU stay between October 2014 and December 2019 were included in this retrospective study. RESULTS: Hematological cancer was found in 77% of patients, and acute respiratory failure was the leading cause of ICU admission (46.3%). The 6-month mortality rate was 69.4%; patients with solid cancer had a higher risk of mortality. Patients who died within 6 months had a poor performance score and a higher SOFA score at admission. The multivariate analysis showed that solid tumors, sepsis on the day of CT, and SOFA score on the day of CT were associated with 6-month mortality. Additionally, 95% of patients who survived the ICU resumed conventional CT, with a higher likelihood of resuming CT among those with hematological cancer. CONCLUSION: Urgent CT in the ICU is feasible in a specific subset of patients, mainly those with hematological cancer, with resumption of the curative treatment regimen after ICU discharge.
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Neoplasias Hematológicas , Leucemia Mieloide Aguda , Adulto , Humanos , Estudios Retrospectivos , Pronóstico , Unidades de Cuidados Intensivos , Mortalidad HospitalariaRESUMEN
In sepsis, personalized immunotherapy is being evaluated as a means of restoring immune function in the most severely affected patients. Biomarkers play a crucial role in this process, as there are no clear clinical indicators of immune dysfunction. Functional testing is considered a gold standard for assessing immune function, but this approach faces analytical challenges in terms of clinical implementation. The use of technician-dependent, time-consuming, home-made protocols often leads to poor standardization. This study represents the first beta testing of a fully automated interferon-γ release assay (IGRA) for monitoring the functionality of antigen-independent T lymphocytes. We observed a significant decrease in IFN-γ release capacity, which was associated with typical alterations in immunological cellular parameters (such as low mHLA-DR expression and decreased CD8 T lymphocyte count), in 22 patients with septic shock. Since the test is performed using whole blood and requires no technician intervention, with results available within 4 h, it may offer new possibilities for monitoring patients with immune alterations in routine clinical conditions. Further investigations in larger cohorts of patients are now needed to validate its clinical potential.
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Sepsis , Choque Séptico , Humanos , Ensayos de Liberación de Interferón gamma , Prueba de Estudio Conceptual , Sepsis/metabolismo , Linfocitos T CD8-positivos/metabolismoRESUMEN
BACKGROUND: Neisseria meningitidis is the leading responsible bacterium of Purpura Fulminans (PF) accounting for two thirds of PF. Skin biopsy is a simple and minimally invasive exam allowing to perform skin culture and polymerase chain reaction (PCR) to detect Neisseria meningitidis. We aimed to assess the sensitivity of skin biopsy in adult patients with meningococcal PF. METHODS: A 17-year multicenter retrospective cohort study including adult patients admitted to the ICU for a meningococcal PF in whom a skin biopsy with conventional and/or meningococcal PCR was performed. RESULTS: Among 306 patients admitted for PF, 195 had a meningococcal PF (64%) with a skin biopsy being performed in 68 (35%) of them. Skin biopsy was performed in median 1 day after the initiation of antibiotic therapy. Standard culture of skin biopsy was performed in 61/68 (90%) patients and grew Neisseria meningitidis in 28 (46%) of them. Neisseria meningitidis PCR on skin biopsy was performed in 51/68 (75%) patients and was positive in 50 (98%) of them. Among these 50 positive meningococcal PCR, five were performed 3 days or more after initiation of antibiotic therapy. Finally, skin biopsy was considered as contributive in 60/68 (88%) patients. Identification of the meningococcal serogroup was obtained with skin biopsy in 48/68 (71%) patients. CONCLUSIONS: Skin biopsy with conventional culture and meningococcal PCR has a global sensitivity of 88% and should be systematically considered in case of suspected meningococcal PF even after the initiation of antimicrobial treatment.
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Meningitis Meningocócica , Infecciones Meningocócicas , Neisseria meningitidis , Púrpura Fulminante , Humanos , Adulto , Púrpura Fulminante/microbiología , Estudios Retrospectivos , Biopsia , Antibacterianos/uso terapéutico , Infecciones Meningocócicas/complicaciones , Meningitis Meningocócica/diagnóstico , Meningitis Meningocócica/microbiologíaRESUMEN
OBJECTIVES: We aimed at assessing the efficacy and safety on antibiotic exposure of a strategy combining a respiratory multiplex PCR (mPCR) with enlarged panel and daily procalcitonin (PCT) measurements, as compared with a conventional strategy, in adult patients who were critically ill with laboratory-confirmed SARS-CoV-2 pneumonia. METHODS: This multicentre, parallel-group, open-label, randomized controlled trial enrolled patients admitted to 13 intensive care units (ICUs) in France. Patients were assigned (1:1) to the control strategy, in which antibiotic streamlining remained at the discretion of the physicians, or interventional strategy, consisting of using mPCR and daily PCT measurements within the first 7 days of randomization to streamline initial antibiotic therapy, with antibiotic continuation encouraged when PCT was >1 ng/mL and discouraged if < 1 ng/mL or decreased by 80% from baseline. All patients underwent conventional microbiological tests and cultures. The primary end point was antibiotic-free days at day 28. RESULTS: Between April 20th and November 23rd 2020, 194 patients were randomized, of whom 191 were retained in the intention-to-treat analysis. Respiratory bacterial co-infection was detected in 48.4% (45/93) and 21.4% (21/98) in the interventional and control group, respectively. The number of antibiotic-free days was 12.0 (0.0; 25.0) and 14.0 (0.0; 24.0) days, respectively (difference, -2.0, (95% CI, -10.6 to 6.6), p=0.89). Superinfection rates were high (51.6% and 48.5%, respectively). Mortality rates and ICU lengths of stay did not differ between groups. DISCUSSION: In severe SARS-CoV-2 pneumonia, the mPCR/PCT algorithm strategy did not affect 28-day antibiotics exposure nor the major clinical outcomes, as compared with routine practice.
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Infecciones Bacterianas , COVID-19 , Infecciones del Sistema Respiratorio , Adulto , Humanos , SARS-CoV-2/genética , Polipéptido alfa Relacionado con Calcitonina/uso terapéutico , COVID-19/diagnóstico , Antibacterianos/uso terapéutico , Reacción en Cadena de la Polimerasa Multiplex , Infecciones del Sistema Respiratorio/diagnóstico , Infecciones del Sistema Respiratorio/tratamiento farmacológico , Infecciones Bacterianas/tratamiento farmacológico , Resultado del Tratamiento , Prueba de COVID-19RESUMEN
Immune responses affiliated with COVID-19 severity have been characterized and associated with deleterious outcomes. These approaches were mainly based on research tools not usable in routine clinical practice at the bedside. We observed that a multiplex transcriptomic panel prototype termed Immune Profiling Panel (IPP) could capture the dysregulation of immune responses of ICU COVID-19 patients at admission. Nine transcripts were associated with mortality in univariate analysis and this 9-mRNA signature remained significantly associated with mortality in a multivariate analysis that included age, SOFA and Charlson scores. Using a machine learning model with these 9 mRNA, we could predict the 28-day survival status with an Area Under the Receiver Operating Curve (AUROC) of 0.764. Interestingly, adding patients' age to the model resulted in increased performance to predict the 28-day mortality (AUROC reaching 0.839). This prototype IPP demonstrated that such a tool, upon clinical/analytical validation and clearance by regulatory agencies could be used in clinical routine settings to quickly identify patients with higher risk of death requiring thus early aggressive intensive care.
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COVID-19 , Enfermedad Crítica , Humanos , ARN Mensajero , Hospitalización , Reacción en Cadena de la PolimerasaRESUMEN
PURPOSE: To determine whether remote ischemic conditioning (RECO), compared to standard care, limits the severity and the consequences of multiple organ failure in patients with septic shock. METHODS: The RECO-Sepsis trial, a prospective, multicenter, randomized, open-label, parallel group trial with blinded assessment of the outcome, was conducted at six intensive care units in France in adult patients with septic shock. Within 12 h after the onset of septic shock, patients were randomized (1:1 ratio) to receive either RECO applied by inflating/deflating (200/0 mmHg for 5/5 min) 4 times a cuff around an arm or a sham procedure every 12 h for 24 h. The primary endpoint was the severity of multiple organ failure assessed by the mean daily Sequential Organ Failure Assessment (SOFA) score from inclusion to the fourth day after inclusion (day 4). Patients were followed for 90 days. RESULTS: Among 180 randomized patients, 178 completed the trial (RECO group: 87; control group: 91) and were included in the intention-to-treat analysis (108 men [60.7%], median age 68 [59-75] years). There was no significant difference in the mean daily SOFA score between the intervention group and the control group (7.2 points [5.2-10.7] versus 7.6 points [4.9-10.7], respectively; p = 0.919). Cumulative mortality within 90 days was 27.6% in the RECO group and 39.6% control group (Log-rank test, p = 0.10; adjusted hazard ratio 0.59, 95% CI, 0.35 to 0.99; p = 0.049). CONCLUSIONS: In patients with septic shock, RECO failed to reduce the severity of organ failures assessed by mean daily SOFA score from inclusion to day 4. Adequately powered trials are needed to assess potential delayed benefits of RECO.