Multicentric investigations of the role in the disease severity of accelerated phospholipid changes in COVID-19 patient airway.

CONTEXT: The changes in host membrane phospholipids are crucial in airway infection pathogenesis. Phospholipase A2 hydrolyzes host cell membranes, producing lyso-phospholipids and free fatty acids, including arachidonic acid (AA), which contributes significantly to lung inflammation. AIM: Follow these changes and their evolution from day 1, day 3 to day 7 in airway aspirates of 89 patients with COVID-19-associated acute respiratory distress syndrome and examine whether they correlate with the severity of the disease. The patients were recruited in three French intensive care units. The analysis was conducted from admission to the intensive care unit until the end of the first week of mechanical ventilation. RESULTS: In the airway aspirates, we found significant increases in the levels of host cell phospholipids, including phosphatidyl-serine and phosphatidyl-ethanolamine, and their corresponding lyso-phospholipids. This was accompanied by increased levels of AA and its inflammatory metabolite prostaglandin E2 (PGE2). Additionally, enhanced levels of ceramides, sphingomyelin, and free cholesterol were observed in these aspirates. These lipids are known to be involved in cell death and/or apoptosis, whereas free cholesterol plays a role in virus entry and replication in host cells. However, there were no significant changes in the levels of dipalmitoyl-phosphatidylcholine, the major surfactant phospholipid. A correlation analysis revealed an association between mortality risk and levels of AA and PGE2, as well as host cell phospholipids. CONCLUSION: Our findings indicate a correlation between heightened cellular phospholipid modifications and variations in AA and PGE2 with the severity of the disease in patients. Nevertheless, there is no indication of surfactant alteration in the initial phases of the illness.

Oncologists' perspective on advance directives, a French national prospective cross-sectional survey - the ADORE study.

BACKGROUND: The often poor prognosis associated with cancer necessitates empowering patients to express their care preferences. Yet, the prevalence of Advance Directives (AD) among oncology patients remains low. This study investigated oncologists' perspectives on the interests and challenges associated with implementing AD. METHODS: A French national online survey targeting hospital-based oncologists explored five areas: AD information, writing support, AD usage, personal perceptions of AD's importance, and respondent's profile. The primary outcome was to assess how frequently oncologists provide patients with information about AD in daily clinical practice. Additionally, we examined factors related to delivering information on AD. RESULTS: Of the 410 oncologists (50%) who responded to the survey, 75% (n = 308) deemed AD relevant. While 36% (n = 149) regularly inform patients about AD, 25% (n = 102) remain skeptical about AD. Among the respondents who do not consistently discuss AD, the most common reason given is the belief that AD may induce anxiety (n = 211/353; 60%). Of all respondents, 90% (n = 367) believe patients require specific information to draft relevant AD. Physicians with experience in palliative care were more likely to discuss AD (43% vs 32.3%, p = 0.027). Previous experience in critical care was associated with higher levels of distrust towards AD (31.5% vs 18.8%, p = 0.003), and 68.5% (n = 281) of the respondents expressed that designating a "person of trust" would be more appropriate than utilizing AD. CONCLUSION: Despite the perceived relevance of AD, only a third of oncologists regularly apprise their patients about them. Significant uncertainty persists about the safety and relevance of AD.

Effectiveness of exercise training on the dyspnoea of individuals with long COVID: A randomised controlled multicentre trial.

BACKGROUND: COVID-19-related acute respiratory distress syndrome (CARDS) is a severe evolution of the Sars-Cov-2 infection and necessitates intensive care. COVID-19 may subsequently be associated with long COVID, whose symptoms can include persistent respiratory symptoms up to 1 year later. Rehabilitation is currently recommended by most guidelines for people with this condition. OBJECTIVES: To evaluate the effects of exercise training rehabilitation (ETR) on dyspnoea and health-related quality of life measures in people with continuing respiratory discomfort following CARDS. METHODS: In this multicentre, two-arm, parallel, open, assessor-blinded, randomised controlled trial, we enroled adults previously admitted with CARDS to 3 French intensive care units who had been discharged at least 3 months earlier and who presented with an mMRC dyspnoea scale score > 1. Participants received either ETR or standard physiotherapy (SP) for 90 days. The primary outcome was dyspnoea, as measured by the Multidimensional Dyspnoea Profile (MDP), at day 0 (inclusion) and after 90 days of physiotherapy. Secondary outcomes were the mMRC and 12-item Short-Form Survey scores. RESULTS: Between August 7, 2020, and January 26, 2022, 487 participants with CARDS were screened for inclusion, of whom 60 were randomly assigned to receive either ETR (n = 27) or SP (n = 33). Mean MDP following ETR was 42% lower than after SP (26.15 vs. 44.76); a difference of -18.61 (95% CI -27.78 to -9.44; p<10-4). CONCLUSION: People who were still suffering from breathlessness three months after being discharged from hospital with CARDS had significantly improved dyspnoea scores when treated with ETR therapy for 90 days unlike those who only received SP. Study registered 29/09/2020 on Clinicaltrials.gov (NCT04569266).

Should We Interfere with the Interleukin-6 Receptor During COVID-19: What Do We Know So Far?

Severe manifestations of COVID-19 consist of acute respiratory distress syndrome due to an initially local reaction leading to a systemic inflammatory response that results in hypoxia. Many therapeutic approaches have been attempted to reduce the clinical consequences of an excessive immune response to viral infection. To date, systemic corticosteroid therapy is still the most effective intervention. More recently, new hope has emerged with the use of interleukin (IL)-6 receptor inhibitors (tocilizumab and sarilumab). However, the great heterogeneity of the methodology and results of published studies obfuscate the true value of this treatment, leading to a confusing synthesis in recent meta-analyses, and the persistence of doubts in terms of patient groups and the appropriate time to treat. Moreover, their effects on the anti-infectious or pro-healing response are still poorly studied. This review aims to clarify the potential role of IL-6 receptor inhibitors in the treatment of severe forms of COVID-19.

Thoracic ultrasound influences physiotherapist's clinical decision-making in respiratory management of critical care patients: a multicentre cohort study.

BACKGROUND: The potential influence of thoracic ultrasound on clinical decision-making by physiotherapists has never been studied. The aim of this study was to assess the impact of thoracic ultrasound on clinical decision-making by physiotherapists for critical care patients. METHODS: This prospective, observational multicentre study was conducted between May 2017 and November 2020 in four intensive care units in France and Australia. All hypoxemic patients consecutively admitted were enrolled. The primary outcome was the net reclassification improvement (NRI), quantifying how well the new model (physiotherapist's clinical decision-making including thoracic ultrasound) reclassifies subjects as compared with an old model (clinical assessment). Secondary outcomes were the factors associated with diagnostic concordance and physiotherapy treatment modification. RESULTS: A total of 151 patients were included in the analysis. The NRI for the modification of physiotherapist's clinical decisions was-40% (95% CI (-56 to -22%), p=0.02). Among the cases in which treatment was changed after ultrasound, 41% of changes were major (n=38). Using a multivariate analysis, the physiotherapist's confidence in their clinical diagnosis was associated with diagnostic concordance (adjusted OR=3.28 95% CI (1.30 to 8.71); p=0.014). Clinical diagnosis involving non-parenchymal conditions and clinical signs reflecting abolished lung ventilation were associated with diagnostic discordance (adjusted OR=0.06 95% CI (0.01 to 0.26), p<0.001; adjusted OR=0.26 95% CI (0.09 to 0.69), p=0.008; respectively). CONCLUSION: Thoracic ultrasound has a high impact on the clinical decision-making process by physiotherapists for critical care patients. TRIAL REGISTRATION NUMBER: NCT02881814; https://clinicaltrials.gov.

Diaphragm function in patients with sepsis and septic shock: A longitudinal ultrasound study.

BACKGROUND: Previous literature on the determinants of diaphragm dysfunction in septic patients is limited. The goal of this study is to assess diaphragm dysfunction in terms of its prevalence and its potential associated factors in septic intensive care unit (ICU) patients. METHODS: This prospective and observational study was conducted between June 2015 and July 2019. Ultrasound measures of diaphragm thickness were performed daily on septic patients. The primary outcome was the prevalence of diaphragm dysfunction at baseline and during the ICU stay. The secondary outcome was the diaphragm thickness. Possible associated factors were prospectively recorded. RESULTS: Fifty patients were enrolled in the study. The prevalence of diaphragm dysfunction was 58%. No diaphragm atrophy was found during the ICU stay. Diaphragm dysfunction was associated with the alteration of consciousness, intra-abdominal sepsis, hypnotics and opioids, and mechanical ventilation. Administration of hypnotics, opioids, and steroids was associated with a decreased diaphragm thickening fraction. Diaphragm dysfunction had no impact on patient outcomes. CONCLUSIONS: Our data reveal a high prevalence of diaphragm dysfunction in septic patients at the onset of sepsis. Administration of hypnotics, opioids, and steroids was associated with the alteration of diaphragm function as well as intra-abdominal sepsis.

General practitioner residents and patients end-of life: involvement and consequences.

BACKGROUND: The ageing of the population and the increased number of chronic diseases are associated with an increased frequency of end of life care in hospital settings. Residents rotating in hospital wards play a major part in their care, regardless of their specialty. General practitioner (GP) residents are confronted to such activities in hospital settings during their training. Our aim was to know how they feel about taking care of dying patients, as end-of-life care are very different from the clinical activity they are trained to. METHODS: We surveyed all GP trainees of "Ile de France". The survey was made of 41 questions regarding advanced directives divided in 7 sections about patients' care, communication, mentoring and repercussion on personal life. The survey was done one time, during two pre-specified days. RESULTS: 525 residents (53.8%) accepted to fulfill the survey. 74.1% of the residents thought that palliative care could have been better. Possible ways of improvements were: a reduction of unreasonable obstinacy (or therapeutic overkill, two terms defined in French law as curative treatment without reasonable hope of efficiency) (59.6%), patient's (210 answers, 40%) and relative's communication (information of patients and relatives about the severity of the disease and risk of death) (199 answers 37.9%). Residents also reported a lack of knowledge regarding end-of-life care specific treatments (411 answers, 79.3%) and 298 (47.2%) wished for better mentoring. Those difficulties were associated with repercussion on their private life (353 answers, 67.2%), particularly with their close relatives (55.4%). Finally, 56.2% of trainees thought that a systematic psychologic follow up should be instituted for those working in "at risk" hospital settings. CONCLUSION: Self-perception management of dying patients by GP resident emphasize their lack of training and supervision. The feeling of suboptimal care is associated with consequences on personal life.

Clustering ICU patients with sepsis based on the patterns of their circulating biomarkers: A secondary analysis of the CAPTAIN prospective multicenter cohort study.

BACKGROUND: Although sepsis is a life-threatening condition, its heterogeneous presentation likely explains the negative results of most trials on adjunctive therapy. This study in patients with sepsis aimed to identify subgroups with similar immune profiles and their clinical and outcome correlates. METHODS: A secondary analysis used data of a prospective multicenter cohort that included patients with early assessment of sepsis. They were described using Predisposition, Insult, Response, Organ failure sepsis (PIRO) staging system. Thirty-eight circulating biomarkers (27 proteins, 11 mRNAs) were assessed at sepsis diagnosis, and their patterns were determined through principal component analysis (PCA). Hierarchical clustering was used to group the patients and k-means algorithm was applied to assess the internal validity of the clusters. RESULTS: Two hundred and three patients were assessed, of median age 64.5 [52.0-77.0] years and SAPS2 score 55 [49-61] points. Five main patterns of biomarkers and six clusters of patients (including 42%, 21%, 17%, 9%, 5% and 5% of the patients) were evidenced. Clusters were distinguished according to the certainty of the causal infection, inflammation, use of organ support, pro- and anti-inflammatory activity, and adaptive profile markers. CONCLUSIONS: In this cohort of patients with suspected sepsis, we individualized clusters which may be described with criteria used to stage sepsis. As these clusters are based on the patterns of circulating biomarkers, whether they might help to predict treatment responsiveness should be addressed in further studies. TRIAL REGISTRATION: The CAPTAIN study was registered on clinicaltrials.gov on June 22, 2011, # NCT01378169.

Characteristics of Hospital Workers Using a Wellbeing Center Implemented During the COVID-19 Pandemic to Prevent the Emotional Impacts of the Crisis.

Introduction: The COVID-19 pandemic has posed an unprecedented challenge worldwide for healthcare workers (HCWs) and other hospital employees. Disruptions in work and personal life may have led to mental health problems. To prevent or limit the severity of such issues, a local initiative has been implemented in a French hospital: a dedicated lounge, also called "Bulle" (literally bubble and meaning safe space) has been created to provide a quiet caring environment and health support. Other similar wellbeing centers have been implemented in other countries, but very little data are available on their practical effectiveness. The purpose of our study was to assess what type of hospital workers have frequented the Bulle and to describe their psychological state in terms of anxiety, depression, and post-traumatic stress disorder (PTSD) just after the first wave, compared to those who had not come to the Bulle. Methods: From 15 July to 1 October 2020, a cross-sectional survey was conducted among all workers, collecting demographic information, professional data (experience and satisfaction), emotional experience during the first wave of COVID-19, and psychological specificities, including a history of burnout or symptoms of anxiety, depression, and PTSD. We asked them if they had accessed the Bulle or not. Results: A total of 675 employees (out of 2,408; 28.0%) fully completed the survey. Approximately 199 respondents (29%) reported having accessed the Bulle during the first wave of the pandemic. Significant symptoms of anxiety, depression, and PTSD were reported by, respectively, 41, 20, and 14% of the participants. Logistic regression analysis showed no relationship between the use of the Bulle and the prevalence of later psychological symptoms. However, employees who benefit from the solicitation of the psychological support team in their hospital unit were secondarily more prone to come to the Bulle [odds ratio (OR), 2.24; 95% confidence interval (95% CI): 1.09; 4.59]. Conclusion: Anxiety, depression, and PTSD were common after the first part of the COVID-19 pandemic, and the attendance in quiet and wellbeing spaces seemed easier with direct internal proactive intervention by psychological teams.

Advance Directives in Oncology and Haematology: A Long Way to Go-A Narrative Review.

Patients living with cancer often experience serious adverse events due to their condition or its treatments. Those events may lead to a critical care unit admission or even result in death. One of the most important but challenging parts of care is to build a care plan according to the patient's wishes, meeting their goals and values. Advance directives (ADs) allow everyone to give their preferences in advance regarding life sustaining treatments, continuation, and withdrawal or withholding of treatments in case one is not able to speak their mind anymore. While the absence of ADs is associated with a greater probability of receiving unwanted intensive care around the end of their life, their existence correlates with the respect of the patient's desires and their greater satisfaction. Although progress has been made to promote ADs' completion, they are still scarcely used among cancer patients in many countries. Several limitations to their acceptance and use can be detected. Efforts should be made to provide tailored solutions for the identified hindrances. This narrative review aims to depict the situation of ADs in the oncology context, and to highlight the future areas of improvement.

Diagnostic accuracy of diaphragm ultrasound to predict weaning outcome: A systematic review and meta-analysis.

BACKGROUND: The accuracy of diaphragm ultrasound for predicting weaning outcome is still debated, despite the publication of numerous studies evaluating this issue. OBJECTIVE: The aim of this systematic review and meta-analysis was to assess the diagnostic accuracy of diaphragm ultrasound for predicting weaning failure in critically ill patients. DESIGN AND DATA SOURCES: MEDLINE, Science direct, Cochrane Library, EMBASE and CENTRAL were searched. Two investigators independently selected studies that met the inclusion criteria, and three extracted data and performed a bias analysis using the Quality Assessment of Diagnostic Accuracy Studies-2 instrument. A bivariate model was used to estimate the pooled results for sensitivity, specificity and diagnostic odds ratio. Sources of heterogeneity were explored, and subgroup analyses were performed. RESULTS: Twenty-eight studies were included in the systematic review, from which 16 studies (816 patients in total) were included in the meta-analysis. The pooled sensitivity, specificity and area under the summary receiver operator characteristic curve were 0.70 (95% CI 0.57-0.80), 0.84 (95% CI 0.73-0.91), and 0.82 (95% Cl 0.78-0.85) for diaphragm thickening fraction, respectively, and 0.71 (95% CI 0.61-0.79), 0.80 (95% CI 0.73-0.86), and 0.82 (95% Cl 0.79-0.86) for diaphragm excursion, respectively. There was substantial heterogeneity among the studies. Meta-regression highlighted significant effects of prevalence of extubation failure, cut-off and risk of bias in flow and timing of the study on diaphragm ultrasound accuracy. By excluding outlier and influential studies, sensitivity was lower and specificity higher for diaphragm thickening fraction. CONCLUSION: The specificity of diaphragm ultrasound for predicting the risk of extubation failure in critically ill patients was moderate-to-high. However, sensitivity was low because weaning is also affected by non-diaphragm-related factors. Further research in subgroups of critically ill patients applying a homogeneous definition of weaning and uniformly conducted measure is needed to assess the accuracy of diaphragm ultrasound. CLINICAL TRIAL REGISTRATION: Registered on http://www.crd.york.ac.uk/PROSPERO as CRD42017058028. Tweetable abstract: Diaphragm ultrasound predicts extubation failure with high specificity. Absence of diaphragm dysfunction does not imply no risk of extubation failure.

Prone position in wards for spontaneous breathing Covid-19 patients: a retrospective study.

The pandemic of coronavirus disease 2019 (Covid-19) caused a large number of non-ventilated hypoxemic patients to require the use of prone position. The aim of this study is to measure the efficiency and tolerance of prone positioning in ward hypoxemic patients treated for Covid-19. This retrospective study included confirmed Covid-19 hypoxemic patients treated by at least one prone position session. Primary outcome was pulse oximetry over inspired oxygen fraction ratio (SpO2/FiO2) before, during, and after prone position. Secondary outcomes were failure, adverse events, and poor tolerance rate. Twenty-seven patients were included. During first, second and third sessions, SpO2/FiO2 ratio was significantly higher during posture than before (p < 0.0001, p < 0.01, and p < 0.001 respectively). Eighteen patients were responders (defined as an improvement of SpO2/FiO2 of more than 50) during the first posture and have a shorter length of hospital stay than non-responder patients. Failure rate was 5%, and poor tolerance and adverse events rates were 8% and 7% respectively. Our study found that prone position in wards improved alveolar exchange during posture and is well tolerated. This technique could be used in any medical ward.

Pneumonia in acute ischemic stroke patients requiring invasive ventilation: Impact on short and long-term outcomes.

OBJECTIVES: To describe the epidemiology and prognostic impact of pneumonia in acute ischemic stroke patients requiring invasive mechanical ventilation. METHODS: Retrospective analysis from a prospective multicenter cohort study of critically ill patients with acute ischemic stroke requiring invasive mechanical ventilation at admission. Impact of pneumonia was investigated using Cox regression for 1-year mortality, and competing risk survival models for ICU mortality censored at 30-days. RESULTS: We included 195 patients. Stroke was supratentorial in 62% and 64% of patients had a Glasgow coma scale score <8 on admission. Mortality at day-30 and 1 year were 56%, and 70%, respectively. Post-stroke pneumonia was identified in 78 (40%) patients, of which 46/78 (59%) episodes were present at ICU admission. Post-stroke pneumonia was associated with an increase in 1-year mortality (adjusted HR 1.49, 95%CI [1.01-2.20]). Post-stroke pneumonia was not associated with ICU mortality but was associated with a 1.6-fold increase in ICU length of stay (CSHR 0.62 [0.39-0.99], p = 0.06). CONCLUSIONS: In ischemic stroke patients requiring invasive ventilation, pneumonia occurred in 40% of cases and was associated with a 49% increase in 1-year mortality. Post-stroke pneumonia did not impact day-30 mortality but increased ICU length of stay.

Advance directives in France: do junior general practitioners want to improve their implementation and usage? A nationwide survey.

BACKGROUND: The doctor-patient relationship has evolved to respect "the autonomy and patients' rights". One of the cornerstones in such autonomy is the opportunity for patients to draw living wills, also known as advance directives (AD). However, information about AD available to patients remains scarce largely due to the lack of involvement of General practitioners for several reasons. The aim of our study was to evaluate current general practitioner residents' (GPR) behavior concerning their role in informing their patients about AD. METHOD: We built a French nationwide survey from GPR class of 2012 to 2014. RESULTS: Two thousand three hundred ten residents completed our survey (21.1% of the total population of GPR during the period). 89.8% declared their willingness to offer patients the opportunity of writing AD. When asked about the usefulness of AD, 73.6% of residents responded that these are a suitable help for patients, but 19.7% considered that AD are essentially geared towards frail patients. Among residents who want to inform patients about AD (n = 2075), 14.7% wanted to involve all patients. Only 20.5% thought that elderly people should be systematically informed about AD. When the question involves other frail people in various disease areas, information seems relevant for 60.1% of GPR considering patient with cancer or malignant hematologic disease and for 56.2% about patients affected by neurodegenerative disease. When considering the routine use of AD, 20.5% of GPR would take them into account only if they are in agreement with the patient's decision. CONCLUSIONS: The results of the survey indicate that GPR would rather choose to decide who should be informed about AD, and when to take AD into account for ethical concerns.

Ventilator-associated pneumonia: The central role of transcolonization.

Ventilator-associated pneumonia remain frequent and serious diseases since they are associated with considerable crude mortality. Pathophysiology is centered on modifications of regional bacterial flora, especially tracheobronchial tree and oropharyngeal sphere. Bacterial migration from an anatomical area to another seems to be the main explanation of these alterations which are called "transcolonization". The association of transcolonization and lack of tightness of the endotracheal tube cuff provides a direct pathway for bacteria from the upper to the subglottic airways, eventually leading to ventilator-associated pneumonia. Although modification of bacterial flora has been largely studied, the mechanism which underlays the ability of the implantation, growing and interactions with the local microbiome that leads to the observed transcolonization remains to be more clearly deciphered. The aim of our review is to emphasize the cornerstone importance of the "transcolonization" as a nosological entity playing a central role in ventilator-associated pneumonia.

Circulating biomarkers may be unable to detect infection at the early phase of sepsis in ICU patients: the CAPTAIN prospective multicenter cohort study.

PURPOSE: Sepsis and non-septic systemic inflammatory response syndrome (SIRS) are the same syndromes, differing by their cause, sepsis being secondary to microbial infection. Microbiological tests are not enough to detect infection early. While more than 50 biomarkers have been proposed to detect infection, none have been repeatedly validated. AIM: To assess the accuracy of circulating biomarkers to discriminate between sepsis and non-septic SIRS. METHODS: The CAPTAIN study was a prospective observational multicenter cohort of 279 ICU patients with hypo- or hyperthermia and criteria of SIRS, included at the time the attending physician considered antimicrobial therapy. Investigators collected blood at inclusion to measure 29 plasma compounds and ten whole blood RNAs, and-for those patients included within working hours-14 leukocyte surface markers. Patients were classified as having sepsis or non-septic SIRS blindly to the biomarkers results. We used the LASSO method as the technique of multivariate analysis, because of the large number of biomarkers. RESULTS: During the study period, 363 patients with SIRS were screened, 84 having exclusion criteria. Ninety-one patients were classified as having non-septic SIRS and 188 as having sepsis. Eight biomarkers had an area under the receiver operating curve (ROC-AUC) over 0.6 with a 95% confidence interval over 0.5. LASSO regression identified CRP and HLA-DRA mRNA as being repeatedly associated with sepsis, and no model performed better than CRP alone (ROC-AUC 0.76 [0.68-0.84]). CONCLUSIONS: The circulating biomarkers tested were found to discriminate poorly between sepsis and non-septic SIRS, and no combination performed better than CRP alone.