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IntroductionLow cardiac output syndrome (LCOS) is a common complication in cardiac surgery, and we evaluated the incidence of its early occurrence after mitral and tricuspid combined cardiac surgery and its associated risk factors.Material and methodRetrospective, single institution study. We included 88 consecutive adult patients with severe mitral insufficiency scheduled for elective mitral and tricuspid valve replacement surgery between January 2015 and November 2018. The primary endpoint was the occurrence of LCOS, defined as the need for inotropic support or circulatory assistance after surgery. The secondary endpoint was mortality at 30 days.ResultsLCOS occurred in 26 patients (29.5%) of the studied patients and its associated risk factors that appeared in the multivariate analysis were chronic kidney failure [adjusted odds ratio (OR) 3.1; 95% confidence interval (CI) 1.0–9.9, p = 0.05], pre-operative left ventricular heart failure (OR 5.3; 95% CI 1.3–10.9, p = 0.002), pre-operative right ventricular heart failure (OR 3.6; 95% CI 1.1–11.5, p = 0.02), and mitral valve replacement (OR 3.9; 95% CI 1.2–12.6, p = 0.03). LCOS affected the survival of patients (HR = 5.5; 95% CI 1.1–27.7 p = 0.04).ConclusionLCOS is a frequent complication after mitral and tricuspid combined surgery and is associated with poor prognosis.

Background: Local infiltration analgesia (LIA) has been advocated for the pain management after total hip arthroplasty (THA). The analgesic benefits of an added pericapsular nerve group (PENG) block remain questionable. Methods: This randomized, single-blind trial enrolled patients undergoing elective THA under general anaesthesia and standardized postoperative analgesia. Patients were allocated to receive either a PENG block (20 mL of ropivacaine 0.475 %) combined with intraoperative LIA (PENG + LIA group, n = 32), or intraoperative LIA alone (LIA group, n = 32). The primary outcome was oral morphine equivalent (OME) consumption at day 1. Secondary outcomes were: pain scores at post anaesthesia care unit (PACU) discharge and on day 2, times for the Timed to Up and Go (TUG) test and measurement of adductor strength on day 1, and patients’ satisfaction using the EVAN-G questionnaire. Results: Compared with LIA alone, PENG + LIA resulted in similar OME consumption on day 1 (78 [51–91.5] mg vs 58 [30–80] mg respectively, median difference (95%CI) of −17 (−34 to 1) mg, p = 0.09). Pain scores and morphine consumption were not different between groups at any time point. TUG and thigh adduction tests were similar between LIA and PENG + LIA groups (respectively 35 [25–48.5] vs 31.5 [19.5–46.5] sec, p = 0.39; and 105 [85–150] vs 100 [80–125] mmHg, p = 0.61). No difference in the patients’ satisfaction was found. Conclusion: The addition of a PENG block to large-volume LIA did not significantly improve the analgesia for elective THA in the setting of an adequate basic postoperative analgesia regimen. The results of the lower limb functional tests confirmed the PENG block to be motor-sparing.

This case report highlights the diagnostic challenges in distinguishing between postpartum headaches caused by preeclampsia and those caused by a suspected dural puncture in a patient with both conditions. The patient had a history of preeclampsia, was well-controlled with labetalol, and received epidural anesthesia using the Tuohy needle during labor. Six hours after delivery, she reported postural headaches, neck tension, and tinnitus, typical symptoms of dural puncture headaches. However, the patient eventually experienced a generalized tonic-clonic seizure and was diagnosed with posterior reversible encephalopathy syndrome and intracranial hypotension. This case highlights the importance of considering multiple underlying factors when analyzing postpartum headaches and the need for prompt and appropriate management to prevent potentially life-threatening complications.

Background Out-of-hospital cardiac arrest (OHCA) represents a major burden for society and health care, with an average incidence in adults of 67 to 170 cases per 100,000 person-years in Europe and in-hospital survival rates of less than 10%. Patients and practitioners would benefit from a prognostication tool for long-term good neurological outcomes. Objective We aim to develop a machine learning (ML) pipeline on a local database to classify patients according to their neurological outcomes and identify prognostic features. Methods We collected clinical and biological data consecutively from 595 patients who presented OHCA and were routed to a single regional cardiac arrest centre in the south of France. We applied recursive feature elimination and ML analyses to identify the main features associated with a good neurological outcome, defined as a Cerebral Performance Category score less than or equal to 2 at six months post-OHCA. Results We identified 12 variables 24 h after admission, capable of predicting a six-month good neurological outcome. The best model (extreme gradient boosting) achieved an AUC of 0.96 and an accuracy of 0.92 in the test cohort. Conclusion We demonstrated that it is possible to build accurate, locally optimised prediction and prognostication scores using datasets of limited size and breadth. We proposed and shared a generic machine-learning pipeline which allows external teams to replicate the approach locally.

IntroductionThe COVID-19 pandemic prompted our team to develop new solutions for performing cardiac surgery without intravenous anesthetics due to a shortage of these drugs. We utilized an anesthetic conserving device (Sedaconda-ACD) to administer total inhaled anesthesia because specific vaporizers were unavailable for administering inhaled agents during cardiopulmonary bypass (CPB) in our center. We documented our experience and postoperative cardiovascular outcomes. The primary outcome was the peak level of troponin, with secondary outcomes encompassing other cardiovascular complications.Material and methodsA single-center retrospective study was conducted. We performed a multivariate analysis with a propensity score. This investigation took place at a large university referral center.ParticipantsAdult patients (age ≥ 18) who underwent elective cardiac surgery with CPB between June 2020 to March 2021.InterventionDuring the inclusion period, two anesthesia protocols for the maintenance of anesthesia coexisted—total inhaled anesthesia with Sedaconda-ACD and our classic protocol with intravenous drugs during and after CPB.Primary endpointTroponin peak level recorded after surgery (highest level recorded within 48 h following the surgery).ResultsOut of the 654 included patients, 454 were analyzed after matching (intravenous group = 297 and inhaled group = 157). No significant difference was found between the groups in postoperative troponin peak levels (723 ng/l vs. 993 ng/l–p = 0.2). Total inhaled anesthesia was associated with a decreased requirement for inotropic medications (OR = 0.53, 95% CI 0.29–0.99, p = 0.04).ConclusionIn our cohort, the Sedaconda-ACD device enabled us to achieve anesthesia without intravenous agents, and we did not observe any increase in postoperative complications. Total inhaled anesthesia with sevoflurane was not associated with a lower incidence of myocardial injury assessed by the postoperative troponin peak level. However, in our cohort, the use of inotropic drugs was lower.

Abstract Background Renal artery Doppler sonography with resistive index (RI) determination is a noninvasive, fast, and reliable diagnostic tool increasingly used in the intensive care unit (ICU) to predict and assess the reversibility of acute kidney injury (AKI). However, interpreting the RI can be challenging due to numerous influencing factors. While some studies have explored various confounding factors, arterial blood gases have received limited attention. Therefore, our study aims to evaluate the impact of arterial blood gases on the RI in the ICU setting. Methods This prospective observational study enrolled ICU patients who required blood gas analysis and had not experienced significant hemodynamic changes recently. The RI was measured using standardized Doppler ultrasound within an hour of the arterial blood gases sampling and analysis. Results A total of sixty-four patients were included in the analysis. Univariate analysis revealed a correlation between the RI and several variables, including PaCO2 (R = 0.270, p = 0.03), age (R = 0.574, p 58 years and PaCO2 were significant factors influencing the RI, with respective odds ratios of 18.67 (p = 0.0003) and 1.132 (p = 0.0267). Conclusion The interpretation of renal arterial RI should take into account thresholds for PaCO2, age, and diastolic arterial pressure. Further studies are needed to develop a comprehensive scoring system that incorporates all these cofactors for a reliable analysis of RI levels. Trial registration This observational study, registered under number 70–0914, received approval from local Ethical Committee of Toulouse University Hospital.

Abstract Background The delayed diagnosis of acute kidney injury (AKI) episodes and the lack of specificity of current single AKI biomarkers hamper its management. Urinary peptidome analysis may help to identify early molecular changes in AKI and grasp its complexity to identify potential targetable molecular pathways. Methods In derivation and validation cohorts totalizing 1170 major cardiac bypass surgery patients and in an external cohort of 1569 intensive care unit (ICU) patients, a peptide-based score predictive of AKI (7-day KDIGO classification) was developed, validated, and compared to the reference biomarker urinary NGAL and NephroCheck and clinical scores. Results A set of 204 urinary peptides derived from 48 proteins related to hemolysis, inflammation, immune cells trafficking, innate immunity, and cell growth and survival was identified and validated for the early discrimination (

Abstract Introduction The transition from medical student to surgical resident is not a simple one. The aim of this study was to report the experience of a university hospital in the organization of the induction course for future surgical residents and the contribution of a video support in the learning of the suture. Material and method We were able to study two consecutive years of students (October 2020 and 2021). Concerning the practical and technical workshops (learning suture) we carried out a comparative study between two groups of students. A group that had video support for learning suture (video group) and a group without video (control group). The evaluation of the suture was performed in a blinded manner by two supervising surgeons. The other practical workshop was drain fixation; the students did not have a video for this workshop. A comparative study was also performed for the drain fixation workshop between the two groups (video group and control group). A program of theoretical courses was also set up. This program is established according to the different future functions of the residents by integrating medico-legal notions and teamwork. Satisfaction questionnaires were given to the students and the answers were given two months after taking up their duties in the hospital (6 questions with Likert scale and 4 free questions). Results The cohort consisted of 58 students (29 each in 2020 and 29 in 2021). Comparative analyses of the evaluation of the suture workshops showed better performance in the video group compared with the group without video. The comparison of these two groups did not show significant differences in the drain fixation workshop. The theoretical teaching was broken down according to the students' future tasks and each speaker was a specialist in his or her field of expertise. The results of the questionnaires showed a desire on the part of the students to increase the time spent on practical workshops and theoretical forensic teaching. Conclusion We were able to show through these two years of a program that we were able to offer a surgical resident preparation course. In addition, we have highlighted the contribution of a video support in the learning curve of the suture.

IntroductionHip fracture is a common clinical problem in geriatric patients often associated with poor postoperative outcomes. Postoperative delirium (POD) and postoperative neurocognitive disorders (NCDs) are particularly frequent. The consequences of these disorders on postoperative recovery and autonomy are not fully described. The aim of this study was to determine the role of POD and NCDs on the need for institutionalization at 3 months after hip fracture surgery.MethodA population-based prospective cohort study was conducted on hip fracture patients between March 2016 and March 2018. The baseline interview, which included a Mini-Mental State Examination (MMSE), was conducted in the hospital after admission for hip fracture. NCDs were appreciated by MMSE scoring evolution (difference between preoperative MMSE and MMSE at day 5 >2 points). POD was evaluated using the Confusion Assessment Method. The primary endpoint was the rate of new institutionalization at 3 months. We used a multivariate analysis to assess the risk of new institutionalization.ResultsA total of 63 patients were included. Thirteen patients (20.6%) were newly institutionalized at 3 months. Two factors were significantly associated with the risk of postoperative institutionalization at 3 months: POD (OR = 5.23; 95% CI 1.1–27.04; p = 0.04) and IADL evolution (OR = 1.8; 95% CI 1.23–2.74; p = 0.003).ConclusionOnly POD but not NCDs was associated with the risk of dependency and institutionalization after hip fracture surgery. The prevention of POD appears to be essential for improving patient outcomes and optimizing the potential for returning home.

During severe sepsis, platelet activation may induce disseminate microvascular thrombosis, which play a key role in critical organ failure. Crucially, most of the studies in this field have explored platelet–leukocyte interactions in animal models, or explored platelets under the spectrum of thrombocytopenia or disseminated intravascular coagulation and have not taken into account the complex interplay that might exist between platelets and leukocytes during human septic shock nor the kinetics of platelet activation. Here, we assessed platelet activation parameters at the admission of patients with sepsis to the intensive care unit (ICU) and 48 hours later. Twenty-two patients were enrolled in the study, thirteen (59.1%) of whom were thrombocytopenic. The control group was composed of twelve infection-free patients admitted during the study period. The activation parameters studied included platelet-leukocyte interactions, assessed by flow cytometry in whole blood, as well as membrane surface and soluble platelet activation markers measured by flow cytometry and dedicated ELISA kits. We also investigated platelet aggregation and secretion responses of patients with sepsis following stimulation, compared to controls. At admission, the level of circulating monocyte-platelet and neutrophil-platelet heterotypic aggregates was significantly higher in sepsis patients compared to controls and returned to a level comparable to controls or even below 48 hours later. Basal levels of CD62P and CD63 platelet membrane exposure at admission and 48 hours later were low and similar to controls. In contrast, plasma level of soluble GPVI and soluble CD40 ligand was significantly increased in septic patients, at the two times of analysis, reflecting previous platelet activation. Platelet aggregation and secretion responses induced by specific agonists were significantly decreased in septic conditions, particularly 48 hours after admission. Hence, we have observed for the first time that critically ill septic patients compared to controls have both an early and durable platelet activation while their circulating platelets are less responsive to different agonists.

Abstract The use of veno-arterial extracorporeal membrane oxygenation (VA ECMO) for the treatment of refractory cardiogenic shock has increased significantly. Nevertheless, early weaning may be advisable to reduce the potential for severe complications. Only a few studies focusing on ECMO weaning predictors are currently available. Our objective was to evaluate factors that may help predict failure during VA ECMO weaning. We included 57 patients on VA ECMO support previously considered suitable for weaning based on specific criteria. Clinical, haemato-chemical and echocardiographic assessment was considered before and after a “weaning test” (ECMO flow 7 days (OR 24 [2–269]) were predictors of weaning failure. The VA ECMO weaning test failed in less than 40% of patients considered suitable for weaning. Clinical and echocardiographic criteria, which are easily accessible by a non-expert intensivist, may help increase the probability of successful weaning.

Background and objectives: To assess lung ultrasound for the diagnosis and monitoring of respiratory complications in thoracic surgery. Methods: Prospective observational study in a University hospital, single institution. Adult patients scheduled for pulmonary resection surgery excluding pneumonectomy. An ultrasound follow-up was performed from the day before the surgery to the third day after surgery with calculation of B-line and lung score (reaeration and loss of aeration scores). Respiratory complications were collected throughout the hospitalization period. Results: Fifty-six patients were included. Eighteen patients presented a respiratory complication (32%), and they presented significantly higher BMI and ASA scores. Patients operated by videothoracoscopy were less at risk of complications. At day 3, a reaeration score ≤ 2 on the ventilated side or ≤ -2 on the operated side, and a B-line score > 6 on the operated side were in favor of a complication. Conclusion: Lung ultrasound can help in the diagnosis of respiratory complications following pulmonary resection surgery.

BackgroundThe ongoing COVID-19 pandemic has highlighted the potential of digital health solutions to adapt the organization of care in a crisis context. ObjectiveOur aim was to describe the relationship between the MyRISK score, derived from self-reported data collected by a chatbot before the preanesthetic consultation, and the occurrence of postoperative complications. MethodsThis was a single-center prospective observational study that included 401 patients. The 16 items composing the MyRISK score were selected using the Delphi method. An algorithm was used to stratify patients with low (green), intermediate (orange), and high (red) risk. The primary end point concerned postoperative complications occurring in the first 6 months after surgery (composite criterion), collected by telephone and by consulting the electronic medical database. A logistic regression analysis was carried out to identify the explanatory variables associated with the complications. A machine learning model was trained to predict the MyRISK score using a larger data set of 1823 patients classified as green or red to reclassify individuals classified as orange as either modified green or modified red. User satisfaction and usability were assessed. ResultsOf the 389 patients analyzed for the primary end point, 16 (4.1%) experienced a postoperative complication. A red score was independently associated with postoperative complications (odds ratio 5.9, 95% CI 1.5-22.3; P=.009). A modified red score was strongly correlated with postoperative complications (odds ratio 21.8, 95% CI 2.8-171.5; P=.003) and predicted postoperative complications with high sensitivity (94%) and high negative predictive value (99%) but with low specificity (49%) and very low positive predictive value (7%; area under the receiver operating characteristic curve=0.71). Patient satisfaction numeric rating scale and system usability scale median scores were 8.0 (IQR 7.0-9.0) out of 10 and 90.0 (IQR 82.5-95.0) out of 100, respectively. ConclusionsThe MyRISK digital perioperative risk score established before the preanesthetic consultation was independently associated with the occurrence of postoperative complications. Its negative predictive strength was increased using a machine learning model to reclassify patients identified as being at intermediate risk. This reliable numerical categorization could be used to objectively refer patients with low risk to teleconsultation.

Fiberoptic intubation for a difficult airway requires significant experience. Traditionally only normal airways were available for high fidelity bronchoscopy simulators. It is not clear if training on difficult airways offers an advantage over training on normal airways. This study investigates the added value of difficult airway scenarios during virtual reality fiberoptic intubation training. A prospective multicentric randomized study was conducted 2019 to 2020, among 86 inexperienced anesthesia residents, fellows and staff. Two groups were compared: Group N (control, n = 43) first trained on a normal airway and Group D (n = 43) first trained on a normal, followed by three difficult airways. All were then tested by comparing their ORSIM® scores on 5 scenarios (1 normal and 4 difficult airways). The final evaluation ORSIM® score for the normal airway testing scenario was significantly higher for group N than group D: median score 76% (IQR 56.5-90) versus 58% (IQR 51.5-69, p = 0.0039), but there was no difference in ORSIM® scores for the difficult intubation testing scenarios. A single exposure to each of 3 different difficult airway scenarios did not lead to better fiberoptic intubation skills on previously unseen difficult airways, when compared to multiple exposures to a normal airway scenario. This finding may be due to the learning curve of approximately 5-10 exposures to a specific airway scenario required to reach proficiency.

During organ transplantation, ischemia/reperfusion injury and pre-formed anti-HLA antibodies are the main cause of delayed graft function and recovery through the activation of the complement system. By supplying oxygen during transplantation, M101 is suspected to avoid complement activation, however, a direct effect exerted by M101 on this pathway is unknown. This was tested by using functional assays (lymphocytotoxic crossmatch test, C3d Luminex-based assay, 50% complement hemolysis [CH50], and 50% alternative complement pathway [AP50/AH50]), and quantitative assays (C3, C3a, C4, C5, C5a, C6, C7, C8, C9 and sC5b-9). M101 interferes with the anti-HLA lymphocytotoxic crossmatch assay, and this effect is complement-dependent as M101 inhibits the classical complement pathway (CH50) in a dose-dependent and stable manner. Such inhibition was independent from a proteolytic effect (fractions C3 to C9) but related to a dose-dependent inhibition of the C3 convertase as demonstrated by exploring downstream the release of the anaphylatoxins (C3a and C5a), C3d, and sC5b-9. The C3 convertase inhibition in the presence of M101 was further demonstrated in the AP50/AH50 assay. In conclusion, the use of M101 avoids the activation of the complement pathway, which constitutes an additional advantage for this extracellular hemoglobin to preserve grafts from ischemia/reperfusion injury and preformed anti-HLA antibodies.

Background Left ventricular overload is frequent under veno‐arterial extracorporeal membrane oxygenation, which is associated with a worsening of the prognosis of these patients. Several left heart decompression (LHD) techniques exist. However, there is no consensus on their timing and type. We aimed to describe characteristics and outcomes of patients undergoing LHD and to compare percutaneous atrioseptostomy (PA) to other LHD techniques. Methods and Results Retrospective analysis was conducted of consecutive and prospectively collected patients supported by veno‐arterial extracorporeal membrane oxygenation for refractory cardiac arrest or cardiogenic shock between January 2015 and April 2018, with a 90‐day follow‐up in our tertiary center. Patients were divided according to the presence of LHD, and then according to its type (PA versus others). Thirty‐nine percent (n=63) of our patients (n=163) required an LHD. Patients with LHD had lower left ventricular ejection fraction, more ischemic cardiomyopathy, and no drug intoxication‐associated cardiogenic shock. PA was frequently used for LHD (41% of first‐line and 57% of second‐line LHD). PA appears safe and fast to realize (6.3 [interquartile range, 5.8–10] minutes) under fluoroscopic and echocardiographic guidance, with no acute complications. PA was associated with fewer neurological complications (12% versus 38%, P=0.02), no need to insert a second LHD (0% versus 19%, P=0.04), and higher 90‐day survival compared with other techniques (42% versus 19%, log‐rank test P=0.02), despite more sepsis (96% versus 73%, P=0.02) and blood transfusions (13.5% versus 7%, P=0.01). Multivariate analysis confirms the association between PA and 90‐day survival (hazard ratio, 2.53 [1.18–5.45], P=0.019). Conclusions LHD was frequently used for patients supported with veno‐arterial extracorporeal membrane oxygenation, especially in cases of ischemic cardiomyopathy and low left ventricular ejection fraction. PA seems to be a safe and efficient LHD technique associated with greater mid‐term survival justifying the pursuit of research on this topic.

Abstract Background Rapid-onset paralytic agents are recommended to achieve muscle relaxation and facilitate tracheal intubation during rapid sequence induction in patients at risk of pulmonary aspiration of gastric contents. However, opioids are frequently used in this setting. The study’s objective is to demonstrate the non-inferiority of remifentanil compared to rapid-onset paralytic agents, in association with an hypnotic drug, for tracheal intubation in patients undergoing procedure under general anesthesia and at risk of pulmonary aspiration of gastric contents. Methods The REMICRUSH (Remifentanil for Rapid Sequence Induction of Anaesthesia) study is a multicenter, single-blinded, non-inferiority randomized controlled trial comparing remifentanil (3 to 4 μg/kg) with rapid-onset paralytic agents (succinylcholine or rocuronium 1 mg/kg) for rapid sequence induction in 1150 adult surgical patients requiring tracheal intubation during general anesthesia. Enrolment started in October 2019 in 15 French anesthesia units. The expected date of the final follow-up is October 2021. The primary outcome is the proportion of successful tracheal intubation without major complications. A non-inferiority margin of 7% was chosen. Analyses of the intent-to-treat and per-protocol populations are planned. Discussion The REMICRUSH trial protocol has been approved by the ethics committee of The Comité de Protection des Personnes Sud-Ouest et Outre-Mer II and will be carried out according to the principles of the Declaration of Helsinki and the Good Clinical Practice guidelines. The results of this study will be disseminated through presentations at scientific conferences and publications in peer-reviewed journals. The REMICRUSH trial is the first randomized controlled trial powered to investigate whether remifentanil with hypnotics is non-inferior to rapid-onset paralytic agents with hypnotic in rapid sequence induction of anesthesia for full stomach patients considering successful tracheal intubation without major complication. Trial registration ClinicalTrials.gov NCT03960801. Registered on May 23, 2019.

Abstract Background The long-term fate of severely injured patients in terms of their quality of life is not well known. Our aim was to assess the quality of life of patients who have suffered moderate to severe trauma and to identify primary factors of long-term quality of life impairment. Methods A prospective monocentric study conducted on a number of patients who were victims of moderate to severe injuries during the year 2012. Patients were selected based on an Injury Severity Score (ISS) more than or equal to 9. Quality of life was assessed by the MOS SF-36 and NHP scores as a primary evaluation criterion. The secondary evaluation criteria were the determination of the socio-economic impact on quality of life and the identification of factors associated with disability. Results Two hundred and eight patients were contacted by e-mail or telephone. Fifty-five patients participated in this study (with a participation level of 26.4%), including 78.2% men, with a median age of 46. Significant alterations in quality of life were observed with the NHP and MOS SF-36 scale, including physical and psychological components. This resulted in a major socio-economic impact as 26% of the patients could not resume their professional activities (n = 10), 20% required retraining in other lines of work, and 36.4% had a disability status. The study showed that scores ≤ 85 on the physical functioning variable of the MOS SF 36 scale was associated with disability. Conclusion More than five years after a moderate to severe injury, patients’ quality of life was significantly impacted, resulting in significant socio-economic consequences. Disability secondary to major trauma seems to be associated with a score ≤ 85 on the physical functioning dimension of the MOS SF-36 scale. This study raises the question of whether or not early rehabilitation programs should be implemented in order to limit the long-term impact of major trauma.

Abstract Background To compare patients hospitalised in the intensive care unit (ICU) after surgery for community-acquired intra-abdominal infection (CA-IAI) and hospital-acquired intra-abdominal infection (HA-IAI) in terms of mortality, severity and complications. Methods Retrospective study including all patients admitted to 2 ICUs within 48 h of undergoing surgery for peritonitis. Results Two hundred twenty-six patients were enrolled during the study period. Patients with CA-IAI had an increased 28-day mortality rate compared to those with HA-IAI (30% vs 15%, respectively (p = 0.009)). At 90 days, the mortality rates were 36.7 and 37.5% in the CA-IAI group and HA-IAI group, respectively, with a similar APACHE II score on admission (median: 21 [15–25] vs. 21 [15–24] respectively, p = 0.63). The patients with HA-IAI had prolonged ICU and hospital stays (median: 17 [7–36] vs. 6[3–12] days, p

Abstract Background In sepsis, the endothelial barrier becomes incompetent, with the leaking of plasma into interstitial tissues. VE-cadherin, an adherens junction protein, is the gatekeeper of endothelial cohesion. Kinins, released during sepsis, induce vascular leakage and vasodilation. They act via two G-protein coupled receptors: B1 (B1R) and B2 (B2R). B1R is inducible in the presence of pro-inflammatory cytokines, endotoxins or after tissue injury. It acts at a later stage of sepsis and elicits a sustained inflammatory response. The aim of our study was to investigate the relationships between B1R and VE-cadherin destabilization in vivo in a later phase of sepsis. Methods Experimental, prospective study in a university research laboratory. We used a polymicrobial model of septic shock by cecal ligation and puncture in C57BL6 male mice or C57BL6 male mice that received a specific B1R antagonist (R-954). We studied the influence of B1R on sepsis-induced vascular permeability 30 h after surgery for several organs, and VE-cadherin expression in the lung and kidneys by injecting R-954 just before surgery. The 96-h survival was determined in mice without treatment or in animals receiving R-954 as a “prophylactic” regimen (a subcutaneous injection of 200 µg/kg, prior to CLP and 24 h after CLP), or as a “curative” regimen (injection of 100 µg/kg at H6, H24 and H48 post-surgery). Results B1R inactivation helps to maintain MAP above 65 mmHg but induces different permeability profiles depending on whether or not organ perfusion is autoregulated. In our model, VE-cadherin was destabilized in vivo during septic shock. At a late stage of sepsis, the B1R blockade reduced the VE-cadherin disruption by limiting eNOS activation. The survival rate for mice that received R-954 after sepsis induction was higher than in animals that received an antagonist as a prophylactic treatment. Conclusions B1R antagonizing reduced mortality in our model of murine septic shock by limiting the vascular permeability induced by VE-cadherin destabilization through maintenance of the macrohemodynamics, consequently limiting organ dysfunctions.

BackgroundThe effects of SARS-CoV-2 (COVID-19) on the myocardium and their role in the clinical course of infected patients are still unknown. The severity of SARS-CoV-2 is driven by hyperinflammation, and the effects of SARS-CoV-2 on the myocardium may be significant. This study proposes to use bedside observations and biomarkers to characterize the association of COVID-19 with myocardial injury. ObjectiveThe aim of the study is to describe the myocardial function and its evolution over time in patients infected with SARS-CoV-2 and to investigate the link between inflammation and cardiac injury. MethodsThis prospective, monocentric, observational study enrolled 150 patients with suspected or confirmed SARS-CoV-2 infection at Toulouse University Hospital, Toulouse, France. Patients admitted to the intensive care unit (ICU), regular cardiologic ward, and geriatric ward of our tertiary university hospital were included during the pandemic period. Blood sampling, electrocardiography, echocardiography, and morphometric and demographic data were prospectively collected. ResultsA total of 100 patients were included. The final enrolment day was March 31, 2020, with first report of results at the end of the first quarter of 2021. The first echocardiographic results at admission of 31 patients of the COCARDE-ICU substudy population show that biological myocardial injury in COVID-19 has low functional impact on left ventricular systolic function. ConclusionsA better understanding of the effects of COVID-19 on myocardial function and its link with inflammation would improve patient follow-up and care. Trial RegistrationClinicaltrials.gov NCT04358952; https://clinicaltrials.gov/ct2/show/NCT04358952 International Registered Report Identifier (IRRID)DERR1-10.2196/24931

Abstract In the intensive care unit, patients are subject to discomforts and pain. Their management is essentially based on pharmacologic approaches. Immersive virtual reality could represent an adjunctive non-invasive and non-pharmacological pain control technique. It is based on real-time interaction with an artificial 360° immersive world using interfaces that enable physical and emotional perceptions to make the user feel better trying to reduce pain perception and to limit anxiety. Evaluation of virtual reality in intensive care unit is lacking and further studies are necessary before to introduce this alternative method for critical patients.

Background and objectives: The frequent onset of hemidiaphragmatic paralysis during interscalene block restricts its use in patients with respiratory insufficiency. Supraclavicular block could be a safe and effective alternative. Our primary objective was to assess the incidence of hemidiaphragmatic paralysis following ultrasound-guided supraclavicular block and compare it to that of interscalene block. Methods: Adults warranting elective shoulder surgery under regional anesthesia (Toulouse University Hospital) were prospectively enrolled from May 2016 to May 2017 in this observational study. Twenty millilitres of 0.375% Ropivacaine were injected preferentially targeted to the “corner pocket”. Diaphragmatic excursion was measured by ultrasonography before and 30 minutes after regional anesthesia. A reduction ≥25% in diaphragmatic excursion during a sniff test defined the hemidiaphragmatic paralysis. Dyspnoea and hypoxaemia were recorded in the recovery room. Predictive factors of hemidiaphragmatic paralysis (gender, age, weight, smoking, functional capacity) were explored. Postoperative pain was also analysed. Results: Forty-two and 43 patients from respectively the supraclavicular block and interscalene block groups were analysed. The incidence of hemidiaphragmatic paralysis was 59.5% in the supraclavicular block group compared to 95.3% in the interscalene block group (p

Abstract Aim Anxiety affects the perception of pain during the postoperative period. A simple evaluation scale could improve the management of this component. The objective of this study was to evaluate the reproducibility and the consistency of a visual analogue scale for anxiety compared with the reference method, the State‐Trait Anxiety Inventory (STAI). Design Observational, prospective, monocentric study of 500 patients in the post‐anaesthetist care unit. Anxiety was evaluated using both the visual analogue scale for anxiety and the STAI in perioperative patients. Consistency between the visual analogue scale for anxiety and the STAI, detection thresholds and factors predicting anxiety were researched. Results A correlation was found between the visual analogue scale for anxiety and the STAI. There was also a correlation between pain and anxiety. Analysis of receiver operating characteristic (ROC) curves showed a visual analogue scale for anxiety threshold of 34/100 allowing the identification of patients with or without anxiety. Predictive factors for anxiety are female gender, use of benzodiazepine in premedication, emergency surgery and significant pain in the post‐anaesthetist care unit. In summary, visual analogue scale for anxiety is a useful tool for detecting the anxiety component of postoperative pain. It could be used in association with covariates of interest to improve anxiety management during the postoperative period.

Abstract Background Tibial fracture is associated with inflammatory reaction leading to severe pain syndrome. Bradykinin receptor activation is involved in inflammatory reactions, but has never been investigated in fracture pain. Methods This study aims at defining the role of B1 and B2-kinin receptors (B1R and B2R) in a closed tibial fracture pain model by using knockout mice for B1R (B1KO) or B2R (B2KO) and wild-type (WT) mice treated with antagonists for B1R (SSR 240612 and R954) and B2R (HOE140) or vehicle. A cyclooxygenase (COX) inhibitor (ketoprofen) and an antagonist (SB366791) of Transient Receptor Potential Vaniloid1 (TRPV1) were also investigated since these pathways are associated with BK-induced pain in other models. The impact on mechanical and thermal hyperalgesia and locomotion was assessed by behavior tests. Gene expression of B1R and B2R and spinal cord expression of c-Fos were measured by RT-PCR and immunohistochemistry, respectively. Results B1KO and B2KO mice demonstrated a reduction in post-fracture pain sensitivity compared to WT mice that was associated with decreased c-Fos expression in the ipsilateral spinal dorsal horn in B2KO. B1R and B2R mRNA and protein levels were markedly enhanced at the fracture site. B1R and B2R antagonists and inhibition of COX and TRPV1 pathways reduced pain in WT. However, the analgesic effect of the COX-1/COX-2 inhibitor disappeared in B1KO and B2KO. In contrast, the analgesic effect of the TRPV1 antagonist persisted after gene deletion of either receptor. Conclusions It is suggested that B1R and B2R activation contributes significantly to tibial fracture pain through COX. Hence, B1R and B2R antagonists appear potential therapeutic agents to manage post fracture pain.

Abstract Background The objective of this study was to determine the main risk factors of Pseudomonas aeruginosa mutation as well as the mechanisms of acquired resistance. Methods We conducted a 2-year prospective study in patients who were carriers of a Pseudomonas aeruginosa strain and who had been admitted to a medical/surgical ICU. Results Of the 153 patients who were included, 34 had a mutation in their strain. In a multivariate analysis, a duration of ventilation > 24 days was a risk factor for mutation (risk ratio 4.29; CI 95% 1.94–9.49) while initial resistance was a protective factor (RR 0.36; CI 95% 0.18–0.71). In a univariate analysis, exposure of P. aeruginosa to ceftazidime was associated with an over-production of AmpC cephalosporinase and exposure to meropenem was associated with impermeability. A segmentation method based on the duration of ventilation (> 24 days), initial resistance, and exposure of strains to ceftazidime made it possible to predict at 83% the occurrence of mutation. Conclusion The duration of ventilation and the presence of resistance as soon as P. aeruginosa is identified are predictive factors of mutation in ICU patients.

Abstract Background Prolonged weaning is a major issue in intensive care patients and tracheostomy is one of the last resort options. Optimized patient-ventilator interaction is essential to weaning. The purpose of this study was to compare patient-ventilator synchrony between pressure support ventilation (PSV) and neurally adjusted ventilatory assist (NAVA) in a selected population of tracheostomised patients. Methods We performed a prospective, sequential, non-randomized and single-centre study. Two recording periods of 60 min of airway pressure, flow, and electrical activity of the diaphragm during PSV and NAVA were recorded in a random assignment and eight periods of 1 min were analysed for each mode. We searched for macro-asynchronies (ineffective, double, and auto-triggering) and micro-asynchronies (inspiratory trigger delay, premature, and late cycling). The number and type of asynchrony events per minute and asynchrony index (AI) were determined. The two respiratory phases were compared using the non-parametric Wilcoxon test after testing the equality of the two variances (F-Test). Results Among the 61 patients analysed, the total AI was lower in NAVA than in PSV mode: 2.1% vs 14% (p

Considering virus-related and drug-induced immunocompromised status of critically ill COVID-19 patients, we hypothesize that these patients would more frequently develop ventilator-associated pneumonia (VAP) than patients with ARDS from other viral causes. We conducted a retrospective observational study in two intensive care units (ICUs) from France, between 2017 and 2020. We compared bacterial co-infection at ICU admission and throughout the disease course of two retrospective longitudinally sampled groups of critically ill patients, who were admitted to ICU for either H1N1 or SARS-CoV-2 respiratory infection and depicted moderate-to-severe ARDS criteria upon admission. Sixty patients in the H1N1 group and 65 in the COVID-19 group were included in the study. Bacterial co-infection at the endotracheal intubation time was diagnosed in 33% of H1N1 and 16% COVID-19 patients (p = 0.08). The VAP incidence per 100 days of mechanical ventilation was 3.4 (2.2–5.2) in the H1N1 group and 7.2 (5.3–9.6) in the COVID-19 group (p < 0.004). The HR to develop VAP was of 2.33 (1.34–4.04) higher in the COVID-19 group (p = 0.002). Ten percent of H1N1 patients and 30% of the COVID-19 patients had a second episode of VAP (p = 0.013). COVID-19 patients have fewer bacterial co-infections upon admission, but the incidence of secondary infections increased faster in this group compared to H1N1 patients.

Background: Several studies suggest an increased incidence of thrombosis in COVID-19 patients. However, evidence on how to prevent and even treat it is scarce. The aim of this study was to compare the cumulative incidence of venous thromboembolism (VTE) of two different methods for lower extremity deep vein thrombosis (LE-DVT) diagnosis: systematic vs. clinically guided complete compression venous ultrasonography (CCUS). We conducted a monocentric, prospective, open-label, non-randomized study. All consecutive patients admitted in three intensive care units (ICUs) of University Hospital of Toulouse for COVID-19 pneumonia were included: one performed systematic screening for LE-DVT, the others did not. The primary outcome was the 21-day cumulative incidence of VTE. The secondary end points were the 21-day cumulative incidences of major bleeding and death.Results: Among the 78 patients included, 27 (34.6%) underwent systematic screening for DVT 7 ± 2 days after ICU admission. Thirty-two patients (41.0%) were diagnosed with VTE, with a 21-day cumulative incidence of 42.3% (95% CI, 31.4–55.2), without difference between screened and non-screened patients (hazard ratio 1.45, 95% CI, 0.72–2.93). In the screened group, the frequency of isolated DVT was higher (25.9 vs. 5.9%, p-value = 0.027), but the frequency of pulmonary embolism was not reduced (25.9 vs. 29.4%, p-value = 0.745). The 21-day cumulative incidences of major bleeding and death were 9.6% (95% CI, 4.7–19.2) and 10.3% (95% CI, 5.0–20.8), respectively, without difference between the two groups.Conclusions: A systematic screening for DVT in patients hospitalized in ICU was not associated with a higher diagnosis of VTE or a reduced diagnosis of PE.

Platelets are mainly known for their key role in hemostasis and thrombosis. However, studies over the last two decades have shown their strong implication in mechanisms associated with inflammation, thrombosis, and the immune system in various neoplastic, inflammatory, autoimmune, and infectious diseases. During sepsis, platelets amplify the recruitment and activation of innate immune cells at the site of infection and contribute to the elimination of pathogens. In certain conditions, these mechanisms can lead to thromboinflammation resulting in severe organ dysfunction. Here, we discuss the interactions of platelets with leukocytes, neutrophil extracellular traps (NETs), and endothelial cells during sepsis. The intrinsic properties of platelets that generate an inflammatory signal through the NOD-like receptor family, pyrin domain-containing 3 (NLRP3) inflammasome are discussed. As an example of immunothrombosis, the implication of platelets in vaccine-induced immune thrombotic thrombocytopenia is documented. Finally, we discuss the role of megakaryocytes (MKs) in thromboinflammation and their adaptive responses.

IntroductionThrombocytopenia is well recognized as a poor prognosis sign associated with increased mortality and prolonged Intensive Care Unit (ICU) stay, particularly in septic patients. Mean platelet volume (MPV) could represent a relevant predictive marker of mortality. Here we investigated whether MPV kinetics during the first 15 days after hospital admission has a potential prognostic value for clinical outcome in septic shock.MethodsWe performed a retrospectively analysis of a cohort of 301 septic patients admitted in ICU. Three-month mortality was the primary endpoint. The prognostic value of the covariates of interest was ascertained by multidimensional analysis. We proposed a classification and regression trees analysis to predict survival probability.ResultsMPV kinetics was significantly different between 90-day survivors and non-survivors when followed during 15 days (except on day 3). 10-day MPV >11.6fL was an independent predictive factor of 90-day mortality (Hazard Ratio (HR) 3.796, 95% Confidence Interval (CI) [1.96-7.35], p = 0.0001) in multivariate analysis. Base excess on day 4 ConclusionMPV increase during the first 15 days after ICU admission in non-survivors was observed during septic shock and 10-day MPV >11.6fL was an independent predictive factor of 90-day mortality. This could be explained by the emergent response to acute platelet loss during septic shock, leading to megakaryocyte rupture to produce new but potentially immature platelets in the circulation. Therefore, continuous monitoring of MPV may be a useful parameter to stratify mortality risk in septic shock.

The French phase 3 trial (OS 2006) testing zoledronic acid, an osteoclast inhibitor, with chemotherapy and surgery did not improve the outcome of patients with osteosarcoma (OS). To understand this unexpected result, the presence of infiltrating immune cells was investigated in 124 pre-therapeutic biopsies of patients enrolled in the trial. The percentage of CD68/CD163 tumor-infiltrating macrophages (TAMs), CD8+ lymphocytes, osteoclasts, and the PD1/PDL-1 checkpoint were assessed by immunohistochemistry. M1/M2 macrophage polarization was characterized by pSTAT1/CMAF staining. The expression of these biomarkers was correlated with clinical outcome. No statistical correlations were found with response to chemotherapy. High CD163 levels (>50% of cells per core; 43.8% of patients) were associated with CMAF nuclear expression and significantly correlated with better overall survival (p = 0.0025) and longer metastasis progression-free survival (MPFS, p = 0.0315) independently of metastatic status (p = 0.002). Only a trend was observed for patients with high CD68-positive cells (p = 0.0582). CD8+ staining was positive in >50% of cases with a median staining of 1%. Lower CD8+ levels were associated with metastatic disease at diagnosis and the presence of CD8-positive cells significantly correlated with improved overall survival in zoledronate-treated patients (p = 0.0415). PD1/PDL-1 staining was negative in >80% of cases and was not correlated with outcome. Finally, CD163-positive TAMs and CD8 positive cells are crucial prognostic biomarkers in OS, whereas PD1/PDL-1 checkpoint plays a minor role. For the first time, we described a correlation between CD8 positive cells and survival in zoledronate-treated patients. The immunohistochemical analysis of the microenvironment in biopsies may represent a novel tool for therapeutic stratification.

Host defense against infection is based on two crucial mechanisms: the inflammatory response and the activation of coagulation. Platelets are involved in both hemostasis and immune response. These mechanisms work together in a complex and synchronous manner making the contribution of platelets of major importance in sepsis. This is a summary of the pathophysiology of sepsis-induced thrombocytopenia, microvascular consequences, platelet-endothelial cells and platelet−pathogens interactions. The critical role of platelets during sepsis and the therapeutic implications are also reviewed.

Abstract Background and objectives: The frequent onset of hemidiaphragmatic paralysis during interscalene block restricts its use in patients with respiratory insufficiency. Supraclavicular block could be a safe and effective alternative. Our primary objective was to assess the incidence of hemidiaphragmatic paralysis following ultrasound-guided supraclavicular block and compare it to that of interscalene block. Methods: Adults warranting elective shoulder surgery under regional anesthesia (Toulouse University Hospital) were prospectively enrolled from May 2016 to May 2017 in this observational study. Twenty millilitres of 0.375% Ropivacaine were injected preferentially targeted to the “corner pocket”. Diaphragmatic excursion was measured by ultrasonography before and 30 minutes after regional anesthesia. A reduction ≥25% in diaphragmatic excursion during a sniff test defined the hemidiaphragmatic paralysis. Dyspnoea and hypoxaemia were recorded in the recovery room. Predictive factors of hemidiaphragmatic paralysis (gender, age, weight, smoking, functional capacity) were explored. Postoperative pain was also analysed. Results: Forty-two and 43 patients from respectively the supraclavicular block and interscalene block groups were analysed. The incidence of hemidiaphragmatic paralysis was 59.5% in the supraclavicular block group compared to 95.3% in the interscalene block group (p < 0.0001). Paradoxical movement of the diaphragm was more common in the interscalene block group (RR = 2, 95% CI 1.4-3; p = 0.0001). A similar variation in oxygen saturation was recorded between patients with and without hemidiaphragmatic paralysis (p = 0.08). No predictive factor of hemidiaphragmatic paralysis could be identified. Morphine consumption and the highest numerical rating scale numerical rating scale (NRS) at 24 hours did not differ between groups. Conclusions: Given the frequent incidence of hemidiaphragmatic paralysis following supraclavicular block, this technique cannot be recommended for patients with an altered respiratory function.