Nicolas Bruder

Excluded volume interactions, which arise from purely steric constraints, play a crucial role in determining the structure, dynamics, and phase behaviour of colloidal suspensions. This is particularly important for non-spherical particles, where orientation-dependent effects also become significant. In this study, we employ depletion-driven phase separation to develop a scalable, size-selective method for purifying spherical and non-spherical colloidal particles. Phase diagrams of charge-stabilised polystyrene spheres ranging in size from 267 to 1008 nm demonstrate that the mixing-demixing transition occurs across a range of surfactant concentrations rather than at a single threshold. Taking advantage of this transition width enables the purification of a single component from binary mixtures at size ratios as low as 1.6 in a single step. When the same approach is applied to coordinated colloidal clusters, tetramers are enriched fifteenfold relative to uncoordinated spheres. Importantly, the efficiency of sorting depends not only on effective size but also on the geometry of the aggregate. For instance, anisotropic, weakly fused clusters separate more efficiently than spherical aggregates because their concave surface curvature is reduced compared to unfused clusters. These findings establish excluded-volume-driven sorting as a practical and scalable route for purifying colloidal building blocks for hierarchical assembly.

Background: Postoperative delirium (POD) is a common surgical complication that increases hospital stay duration, hospitalization costs, readmission rates and mortality. This study aims to describe the incidence of POD in an elderly patient population and to investigate pain assessment as a risk factor for postoperative confusion. Additionally, we aim to determine a predictive model for POD. Methods: We conducted a retrospective, observational, single-center study at La Timone Hospital between September 2020 and September 2021. We included patients aged 65 or older, admitted for scheduled or emergency surgical care, with an expected postoperative stay of three days or more and no history of dementia. Data were collected in three stages of hospitalization: preoperative, perioperative, and postoperative. Preoperative data included medical history and lifestyle; perioperative data included surgical and anesthesia characteristics, and postoperative data were collected. Results: Of the 531 patients admitted for surgical care, we analyzed 109 patients. Among these, 24 (22%) experienced a POD episode within the first three postoperative days. Age, preoperative cognitive impairments, preoperative sensory deficits, and long-term benzodiazepine use were identified as risk factors for POD. A significant difference in pain levels was also observed for all NRS scores during the first three postoperative days. After multivariate analysis, we retained two predictive models for POD. Conclusions: This study identified risk factors for POD and proposed predictive models based on these factors. Two models were particularly notable for their potential use in anesthesia consultations and patient follow-up services to quickly detect patients at risk of POD.

Background: Cardiac injury caused by a sharp object is a medical and surgical therapeutic challenge. Mortality risk factors have been identified but there are major discrepancies in the literature. The aim of this study was to analyse the management of victims of penetrating cardiac injuries before and after admission to hospital and the anatomical characteristics of these injuries in order to facilitate diagnosis of the most critical patients. Methods: To carry out this study, we conducted a retrospective analytical study with epidemiological data on victims of penetrating cardiac injuries. We included two types of patients, with those who underwent autopsy in our institution after death from sharp injury to the heart or great vessels and those who survived with treatment in the emergency department or intensive care unit between January 2015 and February 2022. Results: We included 30 autopsied patients and 12 survivors aged between 18 and 73 years. Higher mortality was associated with prehospital or in-hospital cardiorespiratory arrest (OR = 4, CI [1.71–9.35]), preoperative mechanical ventilation (OR = 10, CI [1.53–65.41]), preoperative catecholamines (OR = 7, CI [1.12–6.29]), preoperative and perioperative adrenaline (OR = 13, CI [1.98–85.46] and [1.98–85.46]), penetrating cardiac injury (OR = 14, CI [2.10–93.22]), multiple cardiac injuries (OR = 1.5, CI [1.05–2.22]) and an Organ Injury Scaling of the American Association for the Surgery of Trauma (AAST-OIS) score of 5 (OR = 2.9, CI [1.04–8.54]; p = 0.0329) with an AUC-ROC curve value of 0.708 (CI [0.543–0.841]). Conclusions: This study identified risk mortality factors in penetrating cardiac injury patients. These findings can help improve the diagnosis and management of these patients. The AAST-OIS score may be a good tool to diagnose critical patients.

Background: The aims of this study were to describe pharmacokinetic/pharmacodynamic target attainment in intensive care unit (ICU) patients treated with continuously infused ß-lactam antibiotics, their associated covariates, and the impact of dosage adjustment. Methods: This prospective, observational, cohort study was performed in three ICUs. Four ß-lactams were continuously infused, and therapeutic drug monitoring (TDM) was performed at days 1, 4, and 7. The primary pharmacokinetic/pharmacodynamic target was an unbound ß-lactam plasma concentration four times above the bacteria’s minimal inhibitory concentration during the whole dosing interval. The demographic and clinical covariates associated with target attainment were evaluated. Results: A total of 170 patients were included (426 blood samples). The percentages of empirical ß-lactam underdosing at D1 were 66% for cefepime, 43% for cefotaxime, 47% for ceftazidime, and 14% for meropenem. Indexed creatinine clearance was independently associated with treatment underdose if increased (adjusted odds ratio per unit, 1.01; 95% CI, 1.00 to 1.01; p = 0.014) or overdose if decreased (adjusted odds ratio per unit, 0.95; 95% CI, 0.94 to 0.97; p < 0.001). Pharmacokinetic/pharmacodynamic target attainment was significantly increased after ß-lactam dosage adjustment between day 1 and day 4 vs. no adjustment (53.1% vs. 26.2%; p = 0.018). Conclusions: This study increases our knowledge on the optimization of ß-lactam therapy in ICU patients. A large inter- and intra-patient variability in plasmatic concentrations was observed, leading to inadequate exposure. A combined indexed creatinine clearance and TDM approach enables adequate dosing for better pharmacokinetic/pharmacodynamic target attainment.

Article: Erector spinal plane block use for rehabilitation in spine surgery: is pain a good endpoint? - Minerva Anestesiologica 2023 Feb 08 - Minerva Medica - Journals

In the early months of the outbreak (2020–2022), COVID-19 was responsible for acute respiratory distress syndrome (ARDS) and an exceptional number of intensive care unit (ICU) admissions. Weaning difficulties from invasive mechanical ventilation (IMV) and many deaths related to COVID-19 were associated with persistent pulmonary hyperinflammation leading to pulmonary fibrosis and sometimes, in the first wave of the pandemic and before the use of dexamethasone was introduced, pulmonary cystic necrosis. A 72-year-old man hospitalized with severe COVID-19 required IMV and died on day 31 of refractory ARDS. Postmortem examination of the lungs found obliterative endotheliitis proximal to pulmonary cystic necrosis. The presence of SARS-CoV-2 envelope and complement/lectin (MASP-2) deposits near the endotheliitis lesions suggested that the virus acted directly on vascular involvement by a complement-mediated mechanism. Together with classic features of ARDS (epithelial lesions and diffuse alveolar damage), endothelial involvement with endotheliitis was the hallmark of severe COVID-19. Corticosteroids and complement blockade were sometimes beneficial for treating severe COVID-19, perhaps by preventing microvascular damage.

Background: Burnout syndrome (BOS) impacts health workers and has become a real public health issue. The primary objective of this observational study was to re-evaluate the incidence of BOS among anesthesiologists and intensivists (AI) in France, ten years after the SESMAT study, a French Physician Health Survey carried out among burnout salaried AI. The secondary objective was to investigate risks factors. Methods: The REPAR survey is an observational study carried in France among AI, residents, and seniors, whatever their main mode of practice, in the framework of a self-questionnaire distributed on the Internet from 11 April 2018 to 1 July 2018. BOS was assessed using the Copenhagen Burnout Inventory (CBI). A score above 50% on two of the dimensions (personal burnout and work-related burnout) indicated BOS, as a main criterion. In order to investigate risks factors, questions were about sociodemographic characteristics, professional and extraprofessional environments, personality and mood using the Major Depression Inventory (MDI). A significance threshold of p < 0.05 was retained. Results: Among 1519 questionnaires received, 1500 completed questionnaires were analyzed. There were 775 men (52%) and 721 women (48%), aged 23 to 74 years. Among those, 24% suffered from BOS, 9% showed depressive symptoms (MDI > 25) and 35% were considering changing jobs or stopping their studies. There was no significant difference with the SESMAT study for the general BOS score. After multivariate analysis, 12 variables were significantly associated with the main criterion. Conclusions: Ten years after the SESMAT study, the incidence of BOS in AI has not decreased in the largest cohort of AI studied to date in France.

Background: For patients presenting with an aneurysmal subarachnoid hemorrhage (aSAH), delayed cerebral ischemia (DCI) is a significant cause of morbidity and mortality. The REACT study is designed to assess the safety and efficacy of clazosentan in preventing clinical deterioration due to DCI in patients with aSAH. Methods: REACT is a prospective, multicenter, randomized phase 3 study that is planned to enroll 400 patients with documented aSAH from a ruptured cerebral aneurysm, randomized 1:1 to 15 mg/hour intravenous clazosentan vs. placebo, in approximately 100 sites and 15 countries. Eligible patients are required to present at hospital admission with CT evidence of significant subarachnoid blood, defined as a thick and diffuse clot that is more than 4 mm in thickness and involves 3 or more basal cisterns. The primary efficacy endpoint is the occurrence of clinical deterioration due to DCI up to 14 days post-study drug initiation. The main secondary endpoint is the occurrence of clinically relevant cerebral infarction at Day 16 post-study drug initiation. Other secondary endpoints include the modified Rankin Scale (mRS) and the Glasgow Outcome Scale-Extended (GOSE) score at Week 12 post-aSAH, dichotomized into poor and good outcome. Radiological results and clinical endpoints are centrally evaluated by independent committees, blinded to treatment allocation. Exploratory efficacy endpoints comprise the assessment of cognition status at 12 weeks and quality of life at 12 and 24 weeks post aSAH. Discussion: In the REACT study, clazosentan is evaluated on top of standard of care to determine if it reduces the risk of clinical deterioration due to DCI after aSAH. The selection of patients with thick and diffuse clots is intended to assess the benefit/risk profile of clazosentan in a population at high risk of vasospasm-related ischemic complications post-aSAH. Trial registration (Additional file 1): ClinicalTrials.gov (NCT03585270). EU Clinical Trial Register (EudraCT Number: 2018–000241-39).