Effects of sevoflurane on lung alveolar epithelial wound healing and survival in a sterile in vitro model of acute respiratory distress syndrome.

Acute respiratory distress syndrome (ARDS) is a serious lung condition that often leads to hospitalization in intensive care units and a high mortality rate. Sevoflurane is a volatile anesthetic with growing interest for sedation in ventilated patients with ARDS. It has been shown to have potential lung-protective effects, such as reduced inflammation and lung edema, or improved arterial oxygenation. In this study, we investigated the effects of sevoflurane on lung injury in cultured human carcinoma-derived lung alveolar epithelial (A549) cells. We found that sevoflurane was associated with improved wound healing after exposure to inflammatory cytokines, with preserved cell proliferation but no effect on cell migration properties. Sevoflurane exposure was also associated with enhanced cell viability and active autophagy in A549 cells exposed to cytokines. These findings suggest that sevoflurane may have beneficial effects on lung epithelial injury by promoting alveolar epithelial wound healing and by influencing the survival and proliferation of A549 epithelial cells in vitro. Further research is needed to confirm these findings and to investigate the key cellular mechanisms explaining sevoflurane's potential effects on lung epithelial injury.

Ventilator-associated pneumonia related to extended-spectrum beta-lactamase producing Enterobacterales during severe acute respiratory syndrome coronavirus 2 infection: risk factors and prognosis.

BACKGROUND: Patients infected with the severe acute respiratory syndrome coronavirus 2 (SARS-COV 2) and requiring mechanical ventilation suffer from a high incidence of ventilator associated pneumonia (VAP), mainly related to Enterobacterales. Data regarding extended-spectrum beta-lactamase producing Enterobacterales (ESBL-E) VAP are scarce. We aimed to investigate risk factors and outcomes of ESBL-E related VAP among critically ill coronavirus infectious disease-19 (COVID-19) patients who developed Enterobacterales related VAP. PATIENTS AND METHODS: We performed an ancillary analysis of a multicenter prospective international cohort study (COVID-ICU) that included 4929 COVID-19 critically ill patients. For the present analysis, only patients with complete data regarding resistance status of the first episode of Enterobacterales related VAP (ESBL-E and/or carbapenem-resistant Enterobacterales, CRE) and outcome were included. RESULTS: We included 591 patients with Enterobacterales related VAP. The main causative species were Enterobacter sp (n = 224), E. coli (n = 111) and K. pneumoniae (n = 104). One hundred and fifteen patients (19%), developed a first ESBL-E related VAP, mostly related to Enterobacter sp (n = 40), K. pneumoniae (n = 36), and E. coli (n = 31). Eight patients (1%) developed CRE related VAP. In a multivariable analysis, African origin (North Africa or Sub-Saharan Africa) (OR 1.7 [1.07-2.71], p = 0.02), time between intubation and VAP (OR 1.06 [1.02-1.09], p = 0.002), PaO2/FiO2 ratio on the day of VAP (OR 0.997 [0.994-0.999], p = 0.04) and trimethoprim-sulfamethoxazole exposure (OR 3.77 [1.15-12.4], p = 0.03) were associated with ESBL-E related VAP. Weaning from mechanical ventilation and mortality did not significantly differ between ESBL-E and non ESBL-E VAP. CONCLUSION: ESBL-related VAP in COVID-19 critically-ill patients was not infrequent. Several risk factors were identified, among which some are modifiable and deserve further investigation. There was no impact of resistance of the first Enterobacterales related episode of VAP on outcome.

Occurrences of post-traumatic stress disorder, anxiety, depression, and burnout syndrome in ICU staff workers after two-year of the COVID-19 pandemic: the international PSY-CO in ICU study.

PURPOSE: The present study aimed at assessing the prevalences of post-traumatic stress disorder (PTSD) (main objective), anxiety, depression, and burnout syndrome (BOS) and their associated factors in intensive care unit (ICU) staff workers in the second year of the COVID-19 pandemic. MATERIALS AND METHODS: An international cross-sectional multicenter ICU-based online survey was carried out among the ICU staff workers in 20 ICUs across 3 continents. ICUs staff workers (both caregivers and non-caregivers) were invited to complete PCL-5, HADS, and MBI questionnaires for assessing PTSD, anxiety, depression, and the different components of BOS, respectively. A personal questionnaire was used to isolate independent associated factors with these disorders. RESULTS: PCL-5, HADS, and MBI questionnaires were completed by 585, 570, and 539 responders, respectively (525 completed all questionnaires). PTSD was diagnosed in 98/585 responders (16.8%). Changing familial environment, being a non-caregiver staff worker, having not being involved in a COVID-19 patient admission, having not been provided with COVID-19-related information were associated with PTSD. Anxiety was reported in 130/570 responders (22.8%). Working in a public hospital, being a woman, being financially impacted, being a non-clinical healthcare staff member, having no theoretical or practical training on individual preventive measures, and fear of managing COVID-19 patients were associated with anxiety. Depression was reported in 50/570 responders (8.8%). Comorbidity at risk of severe COVID-19, working in a public hospital, looking after a child, being a non-caregiver staff member, having no information, and a request for moving from the unit were associated with depression. Having received no information and no adequate training for COVID-19 patient management were associated with all 3 dimensions of BOS. CONCLUSION: The present study confirmed that ICU staff workers, whether they treated COVID-19 patients or not, have a substantial prevalence of psychological disorders.

Convalescent plasma therapy for B-cell-depleted patients with protracted COVID-19.

Anti-CD20 monoclonal antibodies are widely used for the treatment of hematological malignancies or autoimmune disease but may be responsible for a secondary humoral deficiency. In the context of COVID-19 infection, this may prevent the elicitation of a specific SARS-CoV-2 antibody response. We report a series of 17 consecutive patients with profound B-cell lymphopenia and prolonged COVID-19 symptoms, negative immunoglobulin G (IgG)-IgM SARS-CoV-2 serology, and positive RNAemia measured by digital polymerase chain reaction who were treated with 4 units of COVID-19 convalescent plasma. Within 48 hours of transfusion, all but 1 patient experienced an improvement of clinical symptoms. The inflammatory syndrome abated within a week. Only 1 patient who needed mechanical ventilation for severe COVID-19 disease died of bacterial pneumonia. SARS-CoV-2 RNAemia decreased to below the sensitivity threshold in all 9 evaluated patients. In 3 patients, virus-specific T-cell responses were analyzed using T-cell enzyme-linked immunospot assay before convalescent plasma transfusion. All showed a maintained SARS-CoV-2 T-cell response and poor cross-response to other coronaviruses. No adverse event was reported. Convalescent plasma with anti-SARS-CoV-2 antibodies appears to be a very promising approach in the context of protracted COVID-19 symptoms in patients unable to mount a specific humoral response to SARS-CoV-2.

Epidural analgesia information sessions provided by anesthetic nurses: impact on satisfaction and anxiety of parturient women a prospective sequential study.

BACKGROUND: Information on epidural analgesia delivered to parturient women is frequently incomplete, making it difficult for expectant mothers to make an appropriate choice for their delivery. We assessed the impact of a multimodal information session on epidural analgesia delegated to anesthetic nurses on new-mothers' satisfaction. METHODS: We performed a prospective sequential study including parturient women who gave birth with epidural analgesia. During the first period, information on epidural analgesia was delivered by anesthetists during the scheduled anesthesia consultation, according to French standard-of-care. Then, a dedicated information session about epidural analgesia provided by anesthetic nurses was implemented. The primary endpoint was the satisfaction of women with the quality of information received. Main secondary endpoints were knowledge of women about epidural analgesia, anxiety before epidural catheter placement, and satisfaction with delivery. RESULTS: 259 and 298 women were included during the first and second periods respectively, among whom 178 and 188 were analyzed. Information on epidural analgesia delivered by anesthetic nurses was associated with improvement of new-mothers' satisfaction with information received (9 (8-10) vs. 10 (9-10) - p < 0.001). Moreover, information delivered by anesthetic nurses was associated with decreased anxiety before epidural catheter placement (4 (1-8) vs. 3 (1-6) - p = 0.006) and increased satisfaction with delivery (8 (7-10) vs. 9 (8-10) - p = 0.01). Women's knowledge on epidural analgesia was durably increased when information was delivered by anesthetic nurses compared to conventional information by anesthetists. After adjustment, the only variable associated with both new mothers' satisfaction with information and delivery was the information session taught by anesthetic nurses. CONCLUSIONS: Information sessions on epidural analgesia delivered by anesthetic nurses was associated with improved satisfaction of women with their delivery. Such information sessions may be used in maternity wards to improve new-mothers' childbirth experience.

Emerging RNA-Dependent RNA Polymerase Mutation in a Remdesivir-Treated B-cell Immunodeficient Patient With Protracted Coronavirus Disease 2019.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a newly discovered virus for which remdesivir is the only antiviral available. We report the occurrence of a mutation in RdRP (D484Y) following treatment with remdesivir in a 76-year-old female with post-rituximab B-cell immunodeficiency and persistent SARS-CoV-2 viremia. A cure was achieved after supplementation with convalescent plasma.

Blood fibrocytes are associated with severity and prognosis in COVID-19 pneumonia.

Increased blood fibrocytes are associated with a poor prognosis in fibrotic lung diseases. We aimed to determine whether the percentage of circulating fibrocytes could be predictive of severity and prognosis during coronavirus disease 2019 (COVID-19) pneumonia. Blood fibrocytes were quantified by flow cytometry as CD45+/CD15-/CD34+/collagen-1+ cells in patients hospitalized for COVID-19 pneumonia. In a subgroup of patients admitted in an intensive care unit (ICU), fibrocytes were quantified in blood and bronchoalveolar lavage (BAL). Serum amyloid P (SAP), transforming growth factor-ß1 (TGF-ß1), CXCL12, CCL2, and FGF2 concentrations were measured. We included 57 patients in the hospitalized group (median age = 59 yr [23-87]) and 16 individuals as healthy controls. The median percentage of circulating fibrocytes was higher in the patients compared with the controls (3.6% [0.2-9.2] vs. 2.1% [0.9-5.1], P = 0.04). Blood fibrocyte count was lower in the six patients who died compared with the survivors (1.6% [0.2-4.4] vs. 3.7% [0.6-9.2], P = 0.02). Initial fibrocyte count was higher in patients showing a complete lung computed tomography (CT) resolution at 3 mo. Circulating fibrocyte count was decreased in the ICU group (0.8% [0.1-2.0]), whereas BAL fibrocyte count was 6.7% (2.2-15.4). Serum SAP and TGF-ß1 concentrations were increased in hospitalized patients. SAP was also increased in ICU patients. CXCL12 and CCL2 were increased in ICU patients and negatively correlated with circulating fibrocyte count. We conclude that circulating fibrocytes were increased in patients hospitalized for COVID-19 pneumonia, and a lower fibrocyte count was associated with an increased risk of death and a slower resolution of lung CT opacities.

Four-Hour Immunochromatographic Detection of Intestinal Carriage of Carbapenemase-Producing Enterobacteriaceae: a Validation Study.

The increasing incidence of carbapenemase-producing Gram-negative bacilli (C-PGNB) represents a major public health challenge. Rapid detection of digestive colonization with C-PGNB is fundamental to control their spread. We performed the validation of a rapid protocol for C-PGNB detection directly on rectal swabs. We developed a protocol combining enrichment by a rapid selective subculture of the rectal swab medium and realization of a Resist-4 O.K.N.V. K-SeT test on the bacterial pellet obtained. The limit of detection and performances of this protocol were validated in vitro on 52 C-PGNB strains spiked on a calibrated sample suspension and confirmed in clinical settings on 144 rectal swabs sampled from patients with C-PGNB digestive colonization (n = 48) and controls (patients with extended-spectrum beta-lactamase [ESBL] colonization [n = 48] and without carbapenemase/ESBL [n = 48]). The protocol detected, with 100% sensitivity, the presence of the 15 OXA-48-, 14 KPC-, 13 NDM-, and 10 VIM-producing GNB from 103 CFU/ml. The limit of detection was 2 × 102 CFU/ml. Among the 48 C-PGNB-containing rectal swabs of the validation cohort, 46 were accurately detected. False negative were observed for 1 NDM-producing Acinetobacter baumannii strain and 1 OXA-48-producing Escherichia coli strain. The 96 control swabs were negative. Sensitivity and specificity for C-PGNB detection were 97.7% (95% confidence interval [CI], 87.7 to 100) and 100% (95% CI, 96.2 to 100). The negative likelihood ratio was 0.04 (95% CI, 0.01 to 0.16). Considering a C-PGNB digestive colonization prevalence between 0.01% and 0.1%, positive and negative predictive values were 100%. Our protocol is a rapid and low-cost method detecting accurately the digestive colonization with carbapenemase-producing Enterobacteriaceae in 4 h without any requirement for specific equipment.

Human airway trypsin-like protease exerts potent, antifibrotic action in pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is characterized by the deposition of excessive extracellular matrix and the destruction of lung parenchyma, resulting from an aberrant wound-healing response. Although IPF is often associated with an imbalance in protease activity, the mechanisms underlying the sustained repair mechanisms are not fully understood. Here, we addressed the role of the recently identified, membrane-anchored serine protease human airway trypsin-like protease (HAT). In the present study, we show that both HAT expression and activity were up-regulated in human IPF specimens. Next, adenoviral overexpression of HAT before bleomycin challenge attenuated lung injury as well as extracellular matrix deposition in the bleomycin-induced pulmonary fibrosis model. In vitro, HAT prevented specific fibrosis-associated responses in primary human pulmonary fibroblasts and induced the expression of mediators associated with the prostaglandin E2 pathway. Altogether, our findings suggested that HAT could have a protective role in IPF and other fibrotic lung disorders.-Menou, A., Flajolet, P., Duitmen, J., Justet, A., Moog, S., Jaillet, M., Tabèze, L., Solhonne, B., Garnier, M., Mal, H., Mordant, P., Castier, Y., Cazes, A., Sallenave, J.-M., Mailleux, A. A., Crestani, B. Human airway trypsin-like protease exerts potent, antifibrotic action in pulmonary fibrosis.

Meningococcal purpura fulminans and severe myocarditis with clinical meningitis but no meningeal inflammation: a case report.

BACKGROUND: During fulminant meningococcal septicaemia, meningococci are often observed in the cerebrospinal fluid (CSF) although the patients have frequently no meningeal symptoms. Meningococcal meningitis, by contrast, usually features clinical meningeal signs and biochemical markers of inflammation with elevated white blood cell count (pleiocytosis) in the CSF. Cases of typical symptomatic meningitis without these biochemical features are uncommon in adults. CASE PRESENTATION: A 21-year-old male presented with meningococcal purpura fulminans and disseminated intravascular coagulation (DIC) associated with multiple organ dysfunction syndrome requiring hospitalization in the Intensive Care Unit. Despite typical meningeal clinical signs, lumbar puncture showed no pleiocytosis, normal glycorachia and normal proteinorachia, whereas the lactate concentration in the CSF was high (5.8 mmol/L). CSF culture showed a high inoculum of serogroup C meningococci. On day 2, after initial improvement, a recurrence of hypotension led to the diagnosis of acute meningococcal myocarditis, which evolved favourably within a week. During the hospitalization, distal ischemic and necrotic lesions were observed, predominantly on the fingertips, which were treated with local and systemic vasodilators. CONCLUSIONS: We report a rare case of adult meningococcal disease characterized by an intermediate form of meningitis between purulent meningitis and meningeal inoculation from fulminant meningococcal septicaemia, without classical signs of biological inflammation. It highlights the diagnostic value of CSF lactate, which may warrant administration of a meningeal dosing regimen of beta-lactam antibiotics. This case also demonstrates the potential severity of meningococcal myocarditis; we discuss its pathophysiology, which is distinct from other sepsis-related cardiomyopathies. Finally, the observed effects of vasodilators on the meningococcal skin ischemia in this case encourages future studies to assess their efficacy in DIC-associated necrosis.

Optimization of the treatment with beta-lactam antibiotics in critically ill patients-guidelines from the French Society of Pharmacology and Therapeutics (Société Française de Pharmacologie et Thérapeutique-SFPT) and the French Society of Anaesthesia and Intensive Care Medicine (Société Française d'Anesthésie et Réanimation-SFAR).

BACKGROUND: Beta-lactam antibiotics (ßLA) are the most commonly used antibiotics in the intensive care unit (ICU). ICU patients present many pathophysiological features that cause pharmacokinetic (PK) and pharmacodynamic (PD) specificities, leading to the risk of underdosage. The French Society of Pharmacology and Therapeutics (SFPT) and the French Society of Anaesthesia and Intensive Care Medicine (SFAR) have joined forces to provide guidelines on the optimization of beta-lactam treatment in ICU patients. METHODS: A consensus committee of 18 experts from the two societies had the mission of producing these guidelines. The entire process was conducted independently of any industry funding. A list of questions formulated according to the PICO model (Population, Intervention, Comparison, and Outcomes) was drawn-up by the experts. Then, two bibliographic experts analysed the literature published since January 2000 using predefined keywords according to PRISMA recommendations. The quality of the data identified from the literature was assessed using the GRADE® methodology. Due to the lack of powerful studies having used mortality as main judgement criteria, it was decided, before drafting the recommendations, to formulate only "optional" recommendations. RESULTS: After two rounds of rating and one amendment, a strong agreement was reached by the SFPT-SFAR guideline panel for 21 optional recommendations and a recapitulative algorithm for care covering four areas: (i) pharmacokinetic variability, (ii) PK-PD relationship, (iii) administration modalities, and (iv) therapeutic drug monitoring (TDM). The most important recommendations regarding ßLA administration in ICU patients concerned (i) the consideration of the many sources of PK variability in this population; (ii) the definition of free plasma concentration between four and eight times the Minimal Inhibitory Concentration (MIC) of the causative bacteria for 100% of the dosing interval as PK-PD target to maximize bacteriological and clinical responses; (iii) the use of continuous or prolonged administration of ßLA in the most severe patients, in case of high MIC bacteria and in case of lower respiratory tract infection to improve clinical cure; and (iv) the use of TDM to improve PK-PD target achievement. CONCLUSIONS: The experts strongly suggest the use of personalized dosing, continuous or prolonged infusion and therapeutic drug monitoring when administering ßLA in critically ill patients.

Comparison of several methods for pain management after video-assisted thoracic surgery for pneumothorax: an observational study.

BACKGROUND: There is no defined gold standard for pain management after video-assisted thoracic surgery (VATS) for pneumothorax. In addition to systemic analgesia, various loco-regional analgesic techniques have been proposed but remain poorly evaluated in this context. We aimed to assess the analgesic efficacy of several of these techniques for the management of postoperative pain. METHODS: We conducted a monocentric prospective observational cohort study from February 2017 to April 2018 in patients suffering from spontaneous pneumothorax and scheduled for VATS (n = 59). Patients received systemic analgesia (i) alone (n = 15); (ii) combined with a continuous paravertebral block (n = 9); (iii) combined with a continuous serratus plane block (n = 19); or (iv) single-shot serratus plane block (n = 16) as decided by the attending physician. Pain scores and analgesic-related side effects were prospectively collected by an independent observer during the first postoperative 72 h. The primary endpoint criterion was the cumulative oral morphine consumption at the end of the third postoperative day. Statistical analysis used univariate and multivariate step-by-step forward logistic regression models to determine risk factors associated with the main criteria. RESULTS: Mean pain scores and morphine consumption were not significantly different between the 4 groups. In the multivariate analysis, the use of a continuous serratus plane block through a catheter was the only technique associated with a reduced incidence of high-dose oral morphine consumption (OR 0.09-95%CI [0.01-0.79], p = 0.03). CONCLUSION: This study suggests that serratus plane block combined with continuous infusion through a catheter may have some benefits, although further studies are needed to confirm these results and determine the true place of the serratus plane block in pain management after VATS for pneumothorax.

Macrophage Polarization Favors Epithelial Repair During Acute Respiratory Distress Syndrome.

OBJECTIVES: Alveolar macrophage polarization and role on alveolar repair during human acute respiratory distress syndrome remain unclear. This study aimed to determine during human acute respiratory distress syndrome: the alveolar macrophage polarization, the effect of alveolar environment on macrophage polarization, and the role of polarized macrophages on epithelial repair. DESIGN: Experimental ex vivo and in vitro investigations. SETTING: Four ICUs in three teaching hospitals. PATIENTS: Thirty-three patients with early moderate-to-severe acute respiratory distress syndrome were enrolled for assessment of the polarization of alveolar macrophages. INTERVENTIONS: Polarization of acute respiratory distress syndrome macrophages was studied by flow cytometry and quantitative polymerase chain reaction. Modulation of macrophage polarization was studied in vitro using phenotypic and functional readouts. Macrophage effect on repair was studied using alveolar epithelial cells in wound healing models. MEASUREMENTS AND MAIN RESULTS: Ex vivo, alveolar macrophages from early acute respiratory distress syndrome patients exhibited anti-inflammatory characteristics with high CD163 expression and interleukin-10 production. Accordingly, early acute respiratory distress syndrome-bronchoalveolar lavage fluid drives an acute respiratory distress syndrome-specific anti-inflammatory macrophage polarization in vitro, close to that induced by recombinant interleukin-10. Culture supernatants from macrophages polarized in vitro with acute respiratory distress syndrome-bronchoalveolar lavage fluid or interleukin-10 and ex vivo acute respiratory distress syndrome alveolar macrophages specifically promoted lung epithelial repair. Inhibition of the hepatocyte growth factor pathway in epithelial cells and hepatocyte growth factor production in macrophages both reversed this effect. Finally, hepatocyte growth factor and soluble form of CD163 concentrations expressed relatively to macrophage count were higher in bronchoalveolar lavage fluid from acute respiratory distress syndrome survivors. CONCLUSIONS: Early acute respiratory distress syndrome alveolar environment drives an anti-inflammatory macrophage polarization favoring epithelial repair through activation of the hepatocyte growth factor pathway. These results suggest that macrophage polarization may be an important step for epithelial repair and acute respiratory distress syndrome recovery.

Evaluation of early antimicrobial therapy adaptation guided by the BetaLACTA® test: a case-control study.

BACKGROUND: Rapid diagnostic tests detecting microbial resistance are needed for limiting the duration of inappropriateness of empirical antimicrobial therapy (EAT) in intensive care unit patients, besides reducing the use of broad-spectrum antibiotics. We hypothesized that the betaLACTA® test (BLT) could lead to early increase in the adequacy of antimicrobial therapy. METHODS: This was a case-control study. Sixty-one patients with BLT-guided adaptation of EAT were prospectively included, and then matched with 61 "controls" having similar infection characteristics (community or hospital-acquired, and source of infection), in whom EAT was conventionally adapted to antibiogram results. Endpoints were to compare the proportion of appropriate (primary endpoint) and optimal (secondary endpoint) antimicrobial therapies with each of the two strategies, once microbiological sample culture results were available. RESULTS: Characteristics of patients, infections and EAT at inclusion were similar between groups. Nine early escalations of EAT occurred in the BLT-guided adaptation group, reaching 98% appropriateness vs. 77% in the conventional adaptation group (p < 0.01). The BLT reduced the time until escalation of an inappropriate EAT from 50.5 (48-73) to 27 (24-28) hours (p < 0.01). Seventeen early de-escalations occurred in the BLT-guided adaptation group, compared to one in the conventional adaptation group, reducing patients' exposure to broad-spectrum beta-lactam such as carbapenems. In multivariate analysis, use of the BLT was strongly associated with early appropriate (OR = 18 (3.4-333.8), p = 0.006) and optimal (OR = 35.5 (9.6-231.9), p < 0.001) antimicrobial therapies. Safety parameters were similar between groups. CONCLUSIONS: Our study suggests that a BLT-guided adaptation strategy may allow early beta-lactam adaptation from the first 24 hours following the beginning of sepsis management.

Serum Amyloid P Contained in Alveolar Fluid From Patients With Acute Respiratory Distress Syndrome Mediates the Inhibition of Monocyte Differentiation into Fibrocyte.

OBJECTIVE: Alveolar fibrocytes are monocyte-derived mesenchymal cells associated with poor prognosis in patients with acute respiratory distress syndrome. Our aims were to determine the following: 1) the ability of monocytes from acute respiratory distress syndrome patients to differentiate into fibrocytes; 2) the influence of the acute respiratory distress syndrome alveolar environment on fibrocyte differentiation; and 3) mediators involved in this modulation, focusing on serum amyloid P. DESIGN: Experimental in vitro investigation. SETTING: Two ICUs of a teaching hospital. PATIENTS: Twenty-five patients (19 mild-to-severe acute respiratory distress syndrome and six matched ventilated controls without acute respiratory distress syndrome) were enrolled. Six healthy volunteers served as non-ventilated controls. INTERVENTIONS: Peripheral blood mononuclear cells were isolated from acute respiratory distress syndrome, ventilated controls, and non-ventilated controls blood and cultured in vitro. Fibrocytes were counted at basal condition and after culture with broncho-alveolar lavage fluid. Plasma and broncho-alveolar lavage fluid serum amyloid P contents were determined by western blot and enzyme-linked immunosorbent assay. Serum amyloid P was located in normal and acute respiratory distress syndrome lung by immunohistochemistry. MEASUREMENTS AND MAIN RESULTS: Acute respiratory distress syndrome peripheral blood mononuclear cells had a three-fold increased ability to differentiate into fibrocytes compared to ventilated controls or non-ventilated controls. Acute respiratory distress syndrome broncho-alveolar lavage fluid inhibited by 71% (55-94) fibrocyte differentiation compared to saline control. Ventilated controls' broncho-alveolar lavage fluid was a less potent inhibitor (51% [23-66%] of inhibition), whereas non-ventilated controls' broncho-alveolar lavage fluid had no effect on fibrocyte differentiation. Serum amyloid P concentration was decreased in plasma and dramatically increased in broncho-alveolar lavage fluid during acute respiratory distress syndrome. Alveolar serum amyloid P originated, in part, from the release of serum amyloid P associated with lung connective tissue during acute respiratory distress syndrome. Serum amyloid P depletion decreased the inhibitory effect of acute respiratory distress syndrome broncho-alveolar lavage fluid by 60%, whereas serum amyloid P replenishment of serum amyloid P-depleted acute respiratory distress syndrome broncho-alveolar lavage fluid restored their full inhibitory effect. CONCLUSIONS: The presence of fibrocytes in the lung during acute respiratory distress syndrome could result in a balance between higher ability of monocytes to differentiate into fibrocytes and the inhibitory effect of the alveolar environment, mainly dependent on serum amyloid P.

Management of anesthetic emergencies and complications outside the operating room.

PURPOSE OF REVIEW: Anesthesia outside the operating room is commonly uncomfortable and risky. In this setting, anesthetic emergencies or complications may occur. This review aims to report the most recent updates regarding the management of prehospital anesthesia, anesthesia in the trauma and emergency rooms, and anesthesia for endoscopy and interventional radiology. RECENT FINDINGS: After tracheal intubation failure, airway control of outpatients could be achieved by pharmacologically assisted laryngeal mask insertion. Management of traumatic injured patients is best guided in the frame of checklists. Monitoring sedation in this setting is challenging notably because of the threat of haemodynamic instability. Unfortunately, BIS monitoring cannot be recommended to guide sedation in this setting. Ketamine can be used to prevent hypotension during prehospital anesthesia or procedural sedation, especially as its neuroprotective effects have been recently best understood. Target-controlled infusion propofol administration with small concentration increments is adapted to prevent hypotension and hypoxaemia during sedation for gastrointestinal endoscopy and interventional radiology. Target-controlled infusion remifentanil administration is also adapted to many procedures. SUMMARY: Anesthesia outside the operating room requires careful monitoring to avoid side-effects and education of nonanaesthetists when they are involved. A useful tool is to continuously improve the protocols and checklists to make anesthesia in this setting safer.

Corticosteroids induce an early but limited decrease in IL-6 dependent pro-inflammatory responses in critically ill COVID-19 patients.

BACKGROUND: Corticosteroids have become standard of care for COVID-19 but their effect on the systemic immune-inflammatory response has been little investigated. METHODS: Multicenter prospective cohort, including critically ill COVID-19 patients between March and November 2020. C-reactive protein (CRP), lymphocyte count and fibrinogen levels were collected upon hospital admission before initiation of steroid treatment and at ICU admission, three days and seven days later, along with interleukin (IL)-6, IL-10 and tumor necrosis factor-alpha (TNF-α) plasma levels. RESULTS: A hundred and fifty patients were included, 47 received corticosteroids, 103 did not. Median age was 62 [53-70], and 96 (65%) patients were mechanically ventilated. Propensity score matching rendered 45 well-balanced pairs of treated and non-treated patients, particularly on pre-treatment CRP levels. Using a mixed model, CRP (P=0.019), fibrinogen (P=0.003) and lymphocyte counts (P=0.006) remained lower in treated patients over ICU stay. Conversely, there was no significant difference over the ICU stay for Il-6 (P=0.146) and IL-10 (0.301), while TNF- α levels were higher in the treated group (P=0.013). Among corticosteroid-treated patients, CRP (P=0.012), fibrinogen (P=0.041) and lymphocyte count (P=0.004) over time were associated with outcome, whereas plasma cytokine levels were not. CONCLUSIONS: Steroid treatment was associated with an early and sustained decrease in the downstream IL-6-dependent inflammatory signature but an increase in TNF-α levels. In corticosteroid-treated patients, CRP and lymphocyte count were associated with outcome, conversely to plasma cytokine levels. Further research on using these biomarker's kinetics to individualize immunomodulatory treatments is warranted.

Updated meta-analysis on intraoperative inspired fraction of oxygen and the risk of surgical site infection in adults undergoing general and regional anesthesia.

This updated meta-analysis aims at exploring whether the use of systematic high vs low intraoperative oxygen fraction (FiO2) may decrease the incidence of postoperative surgical site infection during general (GA) or regional anesthesia (RA). PubMed, Cochrane CENTRAL, ClinicalTrials.gov databases were searched from January 1st, 1999 and July, 1st 2022, for randomized and quasi-randomized controlled trials that included patients in a high and low FiO2 groups and reported the incidence of SSI. The meta-analysis was conducted with a DerSimonian and Laird random-effects model. Thirty studies (24 for GA and 6 for RA) totaling 18,055 patients (15,871 for GA and 2184 for RA) were included. We have low-to-moderate-quality evidence that high FiO2 (mainly 80%) was not associated with a reduction of SSI incidence compared to low FiO2 (mainly 30%) in all patients (RR 0.90, 95%CI 0.79-1.03). Moderate inconsistency existed between studies (I2 = 38%). Subgroup analyses showed a moderate protective effect in patients undergoing GA (RR 0.86, 95%CI 0.75-0.99) (low level of evidence), while high FiO2 was not associated with a reduction of SSI in patients undergoing RA (RR 1.17, 95%CI 0.90-1.52) (moderate level of evidence). Sensitivity analyses restricted to patients ventilated without nitrous oxide (n = 20 studies), to patients operated from abdominal surgeries (n = 21 studies), and to patients suffering from deep SSI (n = 13 studies), all showed the absence of any significant effect of high FiO2. As a conclusion there is no compelling evidence that high FiO2 can improve postoperative patient's outcome on its own when good SSI prevention practices are properly applied. Recent well-designed and adequately powered randomized controlled trials add further weight to these results.