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BACKGROUND: Inconsistent results from COVID-19 studies raise the issue of patient heterogeneity. OBJECTIVE: The objective of this study was to identify homogeneous subgroups of patients (clusters) using baseline characteristics including inflammatory biomarkers and the extent of lung parenchymal lesions on CT, and to compare their outcomes. DESIGN: Retrospective single-center study. SETTING: Medical ICU of the University Hospital of Clermont-Ferrand, France. PATIENTS: All consecutive adult patients aged greater than or equal to 18 years, admitted between March 20, 2020, and August 31, 2021, for COVID-19 pneumonia. INTERVENTIONS: Characteristics at baseline, during ICU stay, and outcomes at day 60 were recorded. On the chest CT performed at admission the extent of lung parenchyma lesions was established by artificial intelligence software. MEASUREMENTS AND MAIN RESULTS: Clusters were determined by hierarchical clustering on principal components using principal component analysis of admission characteristics including plasma interleukin-6, human histocompatibility leukocyte antigen-DR expression rate on blood monocytes (HLA-DR) monocytic-expression rate (mHLA-DR), and the extent of lung parenchymal lesions. Factors associated with day 60 mortality were investigated by univariate survival analysis. Two hundred seventy patients were included. Four clusters were identified and three were fully described. Cluster 1 (obese patients, with moderate hypoxemia, moderate extent of lung parenchymal lesions, no inflammation, and no down-regulation of mHLA-DR) had a better prognosis at day 60 (hazard ratio [HR] = 0.27 [0.15-0.46], p < 0.01), whereas cluster 2 (older patients with comorbidities, moderate extent of lung parenchyma lesions but significant hypoxemia, inflammation, and down-regulation of mHLA-DR) and cluster 3 (patients with severe parenchymal disease, hypoxemia, inflammatory reaction, and down-regulation of mHLA-DR) had an increased risk of mortality (HR = 2.07 [1.37-3.13], p < 0.01 and HR = 1.52 [1-2.32], p = 0.05, respectively). In multivariate analysis, only clusters 1 and 2 were independently associated with day 60 death. CONCLUSIONS: Three clusters with distinct characteristics and outcomes were identified. Such clusters could facilitate the identification of targeted populations for the next trials.
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COVID-19 , Pneumonia , Adulto , Humanos , Idoso , SARS-CoV-2/metabolismo , Estado Terminal , Estudos Retrospectivos , Inteligência Artificial , Antígenos HLA-DR/metabolismo , Inflamação , Análise por Conglomerados , Hipóxia , Tomografia Computadorizada por Raios XRESUMO
BACKGROUND: There is a lack of information about the organisation and management of clinical research personnel in Europe and of their professional activity in intensive care. We therefore conducted a cross-sectional survey among personnel currently working in a French intensive care research network that involves 41 centres nationwide. The aim of the survey was to describe the personnel's personal and institutional organisation and management, their job perception in terms of satisfaction and stress, and suggestions for improvement. METHODS: Over 3 months in 2023, the research personnel received an electronic questionnaire on their personal and professional profile, past and present training, workplace and functions currently performed, personal knowledge about job skills required, job satisfaction and stress by as measured on a rating scale, and suggested ways of improvement. RESULTS: Ninety seven people replied to the questionnaire (a response rate of 71.3%), of whom 78 (57.3%) were sufficiently involved in intensive care to provide complete answers. This core sample had profiles in line with French recruitment policies and comprised mainly Bachelor/Master graduates, with nurses accounting for only 21.8%. The female to male ratio was 77:23%. Many responders declared to have a shared activity of technician (for investigation) and assistant (for quality control). More than 70% of the responders considered that most of the tasks required of each worker were major. Figures were much lower for project managers, who were few to take part in the survey. On a scale of 10, the median of job satisfaction was 7 for personal work organisation, 6 for training and for institutional organisation, and only 5 for personal career management. The median of job stress was 5 and was inversely correlated with satisfaction with career management. Respect of autonomy, work-sharing activity between investigation and quality control, a better career progression, financial reward for demanding tasks, and participation in unit staff meetings were the main suggestions to improve employee satisfaction. CONCLUSION: This nationwide survey provides a new insight into the activity of French clinical research personnel and points to ways to improve the quality and efficiency of this workforce.
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Descrição de Cargo , Pesquisadores , Humanos , Masculino , Feminino , Estudos Transversais , Unidades de Terapia Intensiva , Satisfação no Emprego , Recursos Humanos , Percepção , Inquéritos e Questionários , Atitude do Pessoal de SaúdeRESUMO
BACKGROUND: Clinical research is essential for the development and progress of therapies and procedures. Intensive care units (ICUs) manage the sickest patients. Numerous clinical trials are organised in ICUs to evaluate new treatments or support techniques. Concomitantly, new professions involved in clinical research set-ups are emerging. AIM: The aim of this scoping review was to identify the nature and extent of research evidence on the organisation of clinical research in ICUs. METHODS: This review focusses on observational and qualitative narrative studies dealing with clinical research organisation in ICUs, with a special interest in structures coordinating research, the roles of clinical research professionals, and the training required. Medline and Embase were analysed between January 2000 and June 2024. Assessment of the study quality was based on the Let Evidence Guide Every New Decision evaluation system and the Newcastle-Ottawa quality assessment scale. RESULTS: Of the 14 studies reviewed, four were narrative and 10 observational descriptive. All were based on cross-sectional surveys. Most studies were carried out in North America, the United Kingdom, and Australia/New Zealand. ICU clinical research professionals were mostly female nurses aged between 31 and 50 years who had a wide diversity of training profiles and performed greatly varied tasks from data collection to publication of the article. Reported job satisfaction depended on the degree of autonomy, the workload, the extent of professional recognition, and opportunities for professional promotion. CONCLUSIONS: The organisation of ICU clinical research reflects considerable diversity in training, tasks, job organisation, and responsibilities.
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OBJECTIVES: To compare the assessment of decision-making capacity of ICU patients by attending clinicians (physicians, nurses, and residents) with a capacity score measured by the Mini-Mental Status Examination, completed by Aid to Capacity Evaluation if necessary. The primary outcome was agreement between physicians' assessments and the score. Secondary outcomes were agreement between nurses' or residents' assessments and the score and identification of factors associated with disagreement. DESIGN: A 1-day prevalence study. SETTING: Nineteen ICUs in France. SUBJECTS: All patients hospitalized in the ICU on the study day and the attending clinicians. INTERVENTIONS: The decision-making capacity of patients was assessed by the attending clinicians and independently by an observer using the score. MEASUREMENTS AND MAIN RESULTS: A total of 206 patients were assessed by 213 attending clinicians (57 physicians, 97 nurses, and 59 residents). Physicians designated more patients as having decision-making capacity (n = 92/206 [45%]) than score (n = 34/206 [17%]; absolute difference 28% [95% CI, 20-37%]; p = 0.001). There was a high disagreement between assessments of all clinicians and score (Kappa coefficient 0.39 [95% CI, 0.29-0.50] for physicians; 0.39 [95% CI, 0.27-0.52] for nurses; and 0.46 [95% CI, 0.35-0.58] for residents). The main factor associated with disagreement was a Glasgow Coma Scale score between 10 and 15 (odds ratio, 2.92 [1.18-7.19], p = 0.02 for physicians; 4.97 [1.50-16.45], p = 0.01 for nurses; and 3.39 [1.12-10.29], p = 0.03 for residents) without differentiating between the Glasgow Coma Scale scores from 10 to 15. CONCLUSIONS: The decision-making capacity of ICU patients was largely overestimated by all attending clinicians as compared with a score. The main factor associated with disagreement was a Glasgow Coma Scale score between 10 and 15, suggesting that clinicians confused consciousness with decision-making capacity.
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Estado Terminal/psicologia , Competência Mental , Testes de Estado Mental e Demência/estatística & dados numéricos , Médicos/estatística & dados numéricos , Tomada de Decisões , Feminino , Escala de Coma de Glasgow , Humanos , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Médicos/psicologia , Estudos ProspectivosRESUMO
BACKGROUND: Tunnelled dialysis catheter (TC) infections are a major health complication and are associated with increased antibiotic consumption, hospital stays, health costs and mortality. Experimental data provide evidence that Ethenox, a mixture of enoxaparine 1000 U/mL in 40% v/v ethanol, could be a promising lock solution. The aim of the study is to compare an interdialytic lock solution of Ethenox with reference lock solutions, unfractionated heparin (UFH) or citrate 4% for the prevention of TCI in hemodialysis patients. METHOD: This study will monitor a multicentre, prospective, single blind, randomized, controlled, parallel group trial. The main inclusion criteria are patients > 18 years old with end-stage renal disease, treated with chronic hemodialysis/hemodiafiltration three times a week, with incident or prevalent non-impregnated internal jugular TCs inserted for at least 2 weeks and able to give informed consent. Exclusion criteria are TCI in the previous 4 weeks and anti-infective treatment for TCI in the previous 2 weeks. Patients will be randomized to receive either study treatment Ethenox in the intervention group or reference solutions in the control group, unfractionated heparin (UFH) or citrate 4% w/v according to usual practice. The primary outcome measure will be time to first TCIs assessed by an endpoint adjudication committee blinded to the study arm according to predefined criteria. Patients will receive the study treatment for up to 12 months. Intention-to-treat analysis of the primary endpoint will be performed with a marginal Cox proportional hazard model. Prospective power calculations indicate that the study will have 90% statistical power to detect a clinical significant two-fold increase in median infection-free survival if 200 patients are recruited into each arm over a period of 24 months. DISCUSSION: Firm evidence of the efficacy of the Ethenox lock in preventing TCI could be of major clinical benefit for patients. The results of this study will allow the development of new guidelines based on a high level of evidence. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03083184 , date of registration March 17 2017 and European Clinical Trials Database Identifier: EudraCT 2016-A00180-51), date of registration July 11 2016.
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Anti-Infecciosos Locais/administração & dosagem , Infecções Relacionadas a Cateter/prevenção & controle , Enoxaparina/administração & dosagem , Etanol/administração & dosagem , Fibrinolíticos/administração & dosagem , Ensaios Clínicos Controlados Aleatórios como Assunto , Diálise Renal/instrumentação , Adulto , Cateteres de Demora/efeitos adversos , Ensaios Clínicos Fase III como Assunto , Intervalo Livre de Doença , Combinação de Medicamentos , França , Humanos , Análise de Intenção de Tratamento , Veias Jugulares , Falência Renal Crônica/terapia , Estudos Multicêntricos como Assunto , Modelos de Riscos Proporcionais , Estudos Prospectivos , Diálise Renal/métodos , Método Simples-CegoRESUMO
BACKGROUND AND AIMS: Neuropathic pain has been shown to be accompanied by cognitive impairment, but the specific impact of postherpetic neuropathic pain on cognitive processes has not been explored. This study aims to evaluate the impact of pain on several domains of cognition in older patients with postherpetic neuralgia (PHN). METHODS: This cross-sectional study (clinicaltrial.gov NCT 00989040) included 84 individuals after signature of informed consent. PARTICIPANTS: 42 patients with PHN and 42 healthy volunteers. Of the 42 PHN patients, 21 received systemic treatment (antidepressants, anticonvulsants, opiates) and 21 had topical treatment with the 5% lidocaine medicated plaster. All participants performed a panel of four cognitive tests: reaction time, semantic memory, decision-making, and visual memory (Cantab, Cambridge). RESULTS: Forty men and 44 women with a mean age of 72 ± 8 years participated. Each PHN patient was matched by age and gender with a healthy volunteer. Vigilance, decision-making, and semantic memory were significantly impaired (P < 0.05) in patients on systemic treatment, especially with antidepressants, while no significant changes were noted between the lidocaine plaster group and their matched controls of healthy volunteers. CONCLUSION: This study shows the deleterious effect of systemic PHN treatment on several domains of cognition. Cognitive impairment associated with pain and antidepressants may be reversed by topical pain management. Topical treatment with 5% lidocaine medicated plaster is a valuable alternative for pain alleviation and maintains cognitive integrity in this vulnerable population.
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Transtornos Cognitivos/epidemiologia , Transtornos Cognitivos/psicologia , Neuralgia Pós-Herpética/epidemiologia , Neuralgia Pós-Herpética/psicologia , Medição da Dor/métodos , Idoso , Idoso de 80 Anos ou mais , Analgésicos/efeitos adversos , Analgésicos/uso terapêutico , Anestésicos Locais/uso terapêutico , Transtornos Cognitivos/induzido quimicamente , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neuralgia Pós-Herpética/tratamento farmacológico , Dor/diagnóstico , Dor/epidemiologia , Dor/psicologiaRESUMO
BACKGROUND: CT-scan and inflammatory and coagulation biomarkers could help in prognostication of COVID-19 in patients on ICU admission. OBJECTIVE: The objectives of this study were to measure the prognostic value of the extent of lung parenchymal lesions on computed tomography (CT) and of several coagulation and inflammatory biomarkers, and to explore the characteristics of the patients depending on the extent of lung parenchymal lesions. DESIGN: Retrospective monocentric observational study achieved on a dataset collected prospectively. SETTING: Medical ICU of the university hospital of Clermont-Ferrand, France. PATIENTS: All consecutive adult patients aged ≥18 years admitted between 20 March, 2020 and 31 August, 2021 for COVID-19 pneumonia. INTERVENTIONS: Characteristics at baseline and during ICU stay, and outcomes at day 60 were recorded. The extent of lung parenchyma lesions observed on the chest CT performed on admission was established by artificial intelligence software. MEASUREMENTS: Several clinical characteristics and laboratory features were collected on admission including plasma interleukin-6, HLA-DR monocytic-expression rate (mHLA-DR), and the extent of lung parenchymal lesions. Factors associated with day-60 mortality were investigated by uni- and multivariate survival analyses. RESULTS: 270 patients were included. Inflammation biomarkers including the levels of neutrophils, CRP, ferritin and Il10 were the indices the most associated with the severity of the extent of the lung lesions. Patients with more extensive lung parenchymal lesions (≥ 75%) on admission had higher CRP serum levels. The extent of lung parenchymal lesions was associated with a decrease in the PaO2/FiO2 ratio(p<0.01), fewer ventilatory-free days (p = 0.03), and a higher death rate at day 60(p = 0.01). Extent of the lesion of more than 75% was independently associated with day-60 mortality (aHR = 1.72[1.06; 2.78], p = 0.03). The prediction of death at day 60 was improved when considering simultaneously biological and radiological markers obtained on ICU admission (AUC = 0.78). CONCLUSIONS: The extent of lung parenchyma lesions on CT was associated with inflammation, and the combination of coagulation and inflammatory biomarkers and the extent of the lesions predicted the poorest outcomes.
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COVID-19 , Unidades de Terapia Intensiva , Pulmão , SARS-CoV-2 , Tomografia Computadorizada por Raios X , Humanos , COVID-19/diagnóstico por imagem , COVID-19/sangue , COVID-19/mortalidade , COVID-19/patologia , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Pulmão/diagnóstico por imagem , Pulmão/patologia , Estudos Retrospectivos , Prognóstico , Biomarcadores/sangue , Adulto , França/epidemiologia , Interleucina-6/sangue , Idoso de 80 Anos ou maisRESUMO
PURPOSE: This study aimed to evaluate the impact on subsequent infections and mortality of an adequate antimicrobial therapy within 48 h after catheter removal in intensive care unit (ICU) patients with positive catheter tip culture. METHODS: We performed a retrospective analysis of prospectively collected data from 29 centers of the OUTCOMEREA network. We developed a propensity score (PS) for adequate antimicrobial treatment, based on expert opinion of 45 attending physicians. We conducted a 1:1 case-cohort study matched on the PS score of being adequately treated. A PS-matched subdistribution hazard model was used for detecting subsequent infections and a PS-matched Cox model was used to evaluate the impact of antibiotic therapy on mortality. RESULTS: We included 427 patients with a catheter tip culture positive with potentially pathogenic microorganisms. We matched 150 patients with an adequate antimicrobial therapy with 150 controls. In the matched population, 30 (10%) subsequent infections were observed and 62 patients died within 30 days. Using subdistribution hazard models, the daily risk to develop subsequent infection up to Day-30 was similar between treated and non-treated groups (subdistribution hazard ratio [sHR] 1.08, 95% confidence interval [CI] 0.62-1.89, p = 0.78). Using Cox proportional hazard models, the 30-day mortality risk was similar between treated and non-treated groups (HR 0.89, 95% CI 0.45-1.74, p = 0.73). CONCLUSIONS: Antimicrobial therapy was not associated with decreased risk of subsequent infection or death in short-term catheter tip colonization in critically ill patients. Antibiotics may be unnecessary for positive catheter tip cultures.
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Infecções Relacionadas a Cateter , Estado Terminal , Unidades de Terapia Intensiva , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Retrospectivos , Infecções Relacionadas a Cateter/tratamento farmacológico , Infecções Relacionadas a Cateter/microbiologia , Infecções Relacionadas a Cateter/mortalidade , Idoso , Unidades de Terapia Intensiva/estatística & dados numéricos , Estudos de Casos e Controles , Modelos de Riscos Proporcionais , Antibacterianos/uso terapêutico , Pontuação de Propensão , Estudos de CoortesRESUMO
Regional citrate anticoagulation use in intermittent hemodialysis is limited by the increased risk of metabolic complications due to faster solute exchanges than with continuous renal replacement therapies. Several simplifications have been proposed. The objective of this study was to validate a mathematical model of hemodialysis anticoagulated with citrate that was then used to evaluate different prescription scenarios on anticoagulant effectiveness (free calcium concentration in dialysis filter) and calcium balance. A study was conducted in hemodialyzed patients with a citrate infusion into the arterial line and a 1.25 mmol/L calcium dialysate. Calcium and citrate concentrations were measured upstream and downstream of the citrate infusion site and in the venous line. The values measured in the venous lines were compared with those predicted by the model using Bland and Altman diagrams. The model was then used with 22 patients to make simulations. The model can predict the concentration of free calcium, bound to citrate or albumin, accurately. Irrespective of the prescription scenario a decrease in free calcium below 0.4 mmol/L was obtained only in a fraction of the dialysis filter. A zero or slightly negative calcium balance was observed, and should be taken into account in case of prolonged use.
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Anticoagulantes , Cálcio , Ácido Cítrico , Diálise Renal , Humanos , Diálise Renal/métodos , Anticoagulantes/administração & dosagem , Feminino , Masculino , Pessoa de Meia-Idade , Cálcio/metabolismo , Cálcio/sangue , Idoso , Modelos Teóricos , Simulação por ComputadorRESUMO
BACKGROUND: The clinical significance of early-onset acute kidney injury (EO-AKI) and recovery in severe COVID-19 intensive care unit (ICU) patients is poorly documented. OBJECTIVE: The aim of the study was to assess the epidemiology and outcome of EO-AKI and recovery in ICU patients admitted for SARS-CoV-2 pneumonia. DESIGN: This was a retrospective single-centre study. SETTING: The study was carried out at the medical ICU of the university hospital of Clermont-Ferrand, France. PATIENTS: All consecutive adult patients aged ≥18 years admitted between 20 March 2020 and 31 August 2021 for SARS-CoV-2 pneumonia were enrolled. Patients with chronic kidney disease, referred from another ICU, and with an ICU length of stay (LOS) ≤72 h were excluded. INTERVENTIONS: EO-AKI was defined on the basis of serum creatinine levels according to the Kidney Disease Improving Global Outcomes criteria, developing ≤7 days. Depending on renal recovery, defined by the normalization of serum creatinine levels, EO-AKI was transient (recovery within 48 h), persistent (recovery between 3 and 7 days) or AKD (no recovery within 7 days after EO-AKI onset). MEASUREMENTS: Uni- and multivariate analyses were performed to determine factors associated with EO-AKI and EO-AKI recovery. MAIN RESULTS: EO-AKI occurred in 84/266 (31.5%) study patients, of whom 42 (50%), 17 (20.2%) and 25 (29.7%) had EO-AKI stages 1, 2 and 3, respectively. EO-AKI was classified as transient, persistent and AKD in 40 (47.6%), 15 (17.8%) and 29 (34.6%) patients, respectively. The 90-day mortality was 87/244 (35.6%) and increased with EO-AKI occurrence and severity: no EO-AKI, 38/168 (22.6%); EO-AKI stage 1, 22/39 (56.4%); stage 2, 9/15 (60%); and stage 3, 18/22 (81.8%) (p < 0.01). The 90-day mortality in patients with transient or persistent AKI and AKD was 20/36 (55.6%), 8/14 (57.1%) and 21/26 (80.8%), respectively (p < 0.01). MAKE-90 occurred in 42.6% of all patients. CONCLUSIONS: In ICU patients admitted for SARS-CoV-2 pneumonia, the development of EO-AKI and time to recovery beyond day 7 of onset were associated with poor outcome.
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OBJECTIVE: COVID 19 is often associated with hypercoagulability and thromboembolic (TE) events. The aim of this study was to assess the characteristics of hypercoagulability and its relationship with new-onset TE events and the composite outcome of need for intubation and/or death in intensive care unit (ICU) patients admitted for COVID. DESIGN: Prospective observational study. SETTING: Monocentric, intensive care, University Hospital of Clermont Ferrand, France. PATIENTS: Patients admitted to intensive care from January 2020 to May 2021 for COVID-19 pneumonia. INTERVENTIONS: Standard hemostatic tests and rotational thromboelastometry (ROTEM) were performed on admission and on day 4. Hypercoagulability was defined by at least one of the following criteria: D-dimers > 3000 µg/dL, fibrinogen > 8 g/L, EXTEM CFT below the normal range, EXTEM A5, MCF, Li 60 above the normal range, and EXTEM G-score ((5000 x MCF) / (100-MCF)) ≥ 11 dyne/cm2. MEASUREMENTS AND MAIN RESULTS: Of the 133 patients included, 17 (12.7%) developed new-onset TE events, and 59 (44.3%) required intubation and/or died in the ICU. ROTEM was performed in 133 patients on day 1 and in 67 on day 4. Hypercoagulability was present on day 1 in 115 (86.4%) patients. None of the hypercoagulability indices were associated with subsequent new-onset TE events on days 1 and 4 nor with the need for intubation and/or ICU death. Hyperfibrinogenemia > 8g/dL, higher D-dimers and higher EXTEM Li 60 on day 4 were predictive of need for intubation and/or of ICU death. CONCLUSIONS: Our study confirmed that most COVID-19 ICU patients have hypercoagulability on admission and almost all on day 4. Hyperfibrinogenemia or fibrinolysis shutdown on day 4 were associated with unfavorable outcome.
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Transtornos da Coagulação Sanguínea , COVID-19 , Hemostáticos , Tromboembolia , Trombofilia , Humanos , Estudos Prospectivos , Estado Terminal , COVID-19/complicações , Trombofilia/complicações , TromboelastografiaRESUMO
BACKGROUND & AIMS: The intensity and duration of the catabolic phase in COVID-19 patients can differ between survivors and non-survivors. The purpose of the study was to assess the determinants of, and association between, nitrogen balance trajectories and outcome in critically ill COVID-19 patients. METHODS: This retrospective monocentric observational study involved patients admitted to the intensive care unit (ICU) of the University Hospital of Clermont Ferrand, France, from January 2020 to May 2021 for COVID-19 pneumonia. Patients were excluded if referred from another ICU, if their ICU length of stay was <72 h, or if they were treated with renal replacement therapy during the first seven days after ICU admission. Data were collected prospectively at admission and during ICU stay. Death was recorded at the end of ICU stay. Comparisons of the time course of nitrogen balance according to outcome were analyzed using two-way ANOVA. At days 3, 5, 7, 10 and 14, uni- and multivariate logistic regression analyses were performed to assess the impact of a non-negative nitrogen-balance on ICU death. To investigate the relationships between nitrogen balance, inflammatory markers and protein intake, linear and non-nonlinear models were run at days 3, 5 and 7, and the amount of protein intake necessary to reach a neutral nitrogen balance was calculated. Subgroup analyses were carried out according to BMI, age, and sex. RESULTS: 99 patients were included. At day 3, a similar negative nitrogen balance was observed in survivors and non-survivors: -16.4 g/d [-26.5, -3.3] and -17.3 g/d [-22.2, -3.8] (p = 0.54). The trajectories of nitrogen balance over time thus differed between survivors and non-survivors (p = 0.01). In survivors, nitrogen balance increased over time, but decreased from day 2 to day 6 in non-survivors, and thereafter increased slowly up to day 14. At days 5 and 7, a non-negative nitrogen-balance was protective from death. Administering higher protein amounts was associated with higher nitrogen balance. CONCLUSION: We report a prolonged catabolic state in COVID patients that seemed more pronounced in non-survivors than in survivors. Our study underlines the need for monitoring urinary nitrogen excretion to guide the amount of protein intake required by COVID-19 patients.
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COVID-19 , Estado Terminal , Humanos , Estado Terminal/terapia , COVID-19/terapia , Estudos Retrospectivos , Unidades de Terapia Intensiva , NitrogênioRESUMO
BACKGROUND: SARS-CoV-2 has been responsible for considerable mortality worldwide, owing in particular to pulmonary failures such as ARDS, but also to other visceral failures and secondary infections. Recent progress in the characterization of the immunological mechanisms that result in severe organ injury led to the emergence of two successive hypotheses simultaneously tested here: hyperinflammation with cytokine storm syndrome or dysregulation of protective immunity resulting in immunosuppression and unrestrained viral dissemination. METHODS: In a prospective observational monocentric study of 134 patients, we analysed a panel of plasma inflammatory and anti-inflammatory cytokines and measured monocyte dysregulation via their membrane expression of HLA-DR. We first compared the results of patients with moderate forms hospitalized in an infectious disease unit with those of patients with severe forms hospitalized in an intensive care unit. In the latter group of patients, we then analysed the differences between the surviving and non-surviving groups and between the groups with or without secondary infections. FINDINGS: Higher blood IL-6 levels, lower quantitative expression of HLA-DR on blood monocytes and higher IL-6/mHLA-DR ratios were statistically associated with the risk of severe forms of the disease and among the latter with death and the early onset of secondary infections. INTERPRETATION: The unique immunological profile in patients with severe COVID-19 corresponds to a moderate cytokine inflammation associated with severe monocyte dysregulation. Individuals with major CSS were rare in our cohort of hospitalized patients, especially since the use of corticosteroids, but formed a very severe subgroup of the disease. FUNDING: None.
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COVID-19/patologia , Citocinas/sangue , Monócitos/metabolismo , Idoso , COVID-19/complicações , COVID-19/virologia , Síndrome da Liberação de Citocina/etiologia , Feminino , Antígenos HLA-DR/metabolismo , Humanos , Unidades de Terapia Intensiva , Interleucina-6/sangue , Masculino , Pessoa de Meia-Idade , Monócitos/citologia , Monócitos/imunologia , Estudos Prospectivos , SARS-CoV-2/isolamento & purificação , Índice de Gravidade de DoençaRESUMO
INTRODUCTION: Multiplex polymerase chain reaction (mPCR) for respiratory virus testing is increasingly used in community-acquired pneumonia (CAP), however data on one-year outcome in intensive care unit (ICU) patients with reference to the causative pathogen are scarce. MATERIALS AND METHODS: We performed a single-center retrospective study in 123 ICU patients who had undergone respiratory virus testing for CAP by mPCR and with known one-year survival status. Functional status including dyspnea (mMRC score), autonomy (ADL Katz score) and need for new home-care ventilatory support was assessed at a one-year post-ICU follow-up. Mortality rates and functional status were compared in patients with CAP of a bacterial, viral or unidentified etiology one year after ICU admission. RESULTS: The bacterial, viral and unidentified groups included 19 (15.4%), 37 (30.1%), and 67 (54.5%) patients, respectively. In multivariate analysis, one-year mortality in the bacterial group was higher compared to the viral group (HR 2.92, 95% CI 1.71-7.28, p = 0.02) and tended to be higher compared to the unidentified etiology group (p = 0.06); but no difference was found between the viral and the unidentified etiology group (p = 0.43). In 64/83 one-year survivors with a post-ICU follow-up consultation, there were no differences in mMRC score, ADL Katz score and new home-care ventilatory support between the groups (p = 0.52, p = 0.37, p = 0.24, respectively). Severe dyspnea (mMRC score = 4 or death), severe autonomy deficiencies (ADL Katz score ≤ 2 or death), and major adverse respiratory events (new home-care ventilatory support or death) were observed in 52/104 (50.0%), 47/104 (45.2%), and 65/104 (62.5%) patients, respectively; with no difference between the bacterial, viral and unidentified group: p = 0.58, p = 0.06, p = 0.61, respectively. CONCLUSIONS: CAP of bacterial origin had a poorer outcome than CAP of viral or unidentified origin. At one-year, impairment of functional status was frequently observed, with no difference according to the etiology.