Prior participation as a standardized patient improves OSCE scores of third-year medical students: A pilot comparative study at Université Paris Cité Medical School.

OBJECTIVE: Objective structured clinical examinations (OSCE) are one of the main modalities of skills' assessment of medical students. We aimed to evaluate the educational value of the participation of third-year medical students in OSCE as standardized patients. METHODS: We conducted a pilot OSCE session where third-year students participated in sixth-year students' OSCE as standardized patients (cases). Their scores in their own subsequent OSCE exams were compared with third-year students who had not participated (controls). Students' perceptions (stress, preparedness, ease) regarding their OSCE were compared with self-administered questionnaires. RESULTS: A total of 42 students were included (9 cases and 33 controls). Median [IQR] overall score (out of 20 points) obtained by the cases was 17 [16.3-18] versus 14.5 [12.7-16.3] for controls (p < 0.001). Students' perception of their evaluation (difficulty, stress, communication) was not significantly different between cases and controls. Most cases agreed that their participation was beneficial in reducing their stress (67%), increasing their preparedness (78%) and improving their communication skills (100%). All cases agreed that this participation should be offered more widely. CONCLUSION: Students' participation in OSCE as standardized patients led to better performance on their own OSCE and were considered beneficial. This approach could be more broadly generalized to improve student performance.

Effect of flow change on brain injury during an experimental model of differential hypoxaemia in cardiogenic shock supported by extracorporeal membrane oxygenation.

Differential hypoxaemia (DH) is common in patients supported by femoral veno-arterial extracorporeal membrane oxygenation (V-A ECMO) and can cause cerebral hypoxaemia. To date, no models have studied the direct impact of flow on cerebral damage. We investigated the impact of V-A ECMO flow on brain injury in an ovine model of DH. After inducing severe cardiorespiratory failure and providing ECMO support, we randomised six sheep into two groups: low flow (LF) in which ECMO was set at 2.5 L min-1 ensuring that the brain was entirely perfused by the native heart and lungs, and high flow (HF) in which ECMO was set at 4.5 L min-1 ensuring that the brain was at least partially perfused by ECMO. We used invasive (oxygenation tension-PbTO2, and cerebral microdialysis) and non-invasive (near infrared spectroscopy-NIRS) neuromonitoring, and euthanised animals after five hours for histological analysis. Cerebral oxygenation was significantly improved in the HF group as shown by higher PbTO2 levels (+ 215% vs - 58%, p = 0.043) and NIRS (67 ± 5% vs 49 ± 4%, p = 0.003). The HF group showed significantly less severe brain injury than the LF group in terms of neuronal shrinkage, congestion and perivascular oedema (p < 0.0001). Cerebral microdialysis values in the LF group all reached the pathological thresholds, even though no statistical difference was found between the two groups. Differential hypoxaemia can lead to cerebral damage after only a few hours and mandates a thorough neuromonitoring of patients. An increase in ECMO flow was an effective strategy to reduce such damages.

A mock circulation loop to evaluate differential hypoxemia during peripheral venoarterial extracorporeal membrane oxygenation.

INTRODUCTION: Peripheral veno-arterial extracorporeal membrane oxygenation (VA ECMO) creates a retrograde flow along the aorta competing with the left ventricle (LV) in the so-called 'mixing zone' (MZ). Detecting it is essential to understand which of the LV or the ECMO flow perfuses the upper body - particularly the brain and the coronary arteries - in case of differential hypoxemia (DH). METHODS: We described a mock circulation loop (MCL) that enabled experimental research on DH. We recreated the three clinical situations relevant to clinicians: where the brain is either totally perfused by the ECMO or the LV or both. In a second step, we used this model to investigate two scenarios to diagnose DH: (i) pulse pressure and (ii) thermodilution via injection of cold saline in the ECMO circuit. RESULTS: The presented MCL was able to reproduce the three relevant mixing zones within the aortic arch, thus allowing to study DH. Pulse pressure was unable to detect location of the MZ. However, the thermodilution method was able to detect whether the brain was totally perfused by the ECMO or not. CONCLUSION: We validated an in-vitro differential hypoxemia model of cardiogenic shock supported by VA ECMO. This MCL could be used as an alternative to animal studies for research scenarios.

Impact of prior antibiotic therapy on severe necrotizing soft-tissue infections in ICU patients: results from a French retrospective and observational study.

Necrotizing soft-tissue infection (NSTI) is a life-threatening pathology that often requires management in intensive care unit (ICU). Therapies consist of early diagnosis, adequate surgical source control, and antimicrobial therapy. Whereas guidelines underline the need for appropriate routine microbiological cultures before starting antimicrobial therapy in patients with suspected sepsis or septic shock, delaying adequate therapy also strongly increases mortality. The aim of the present study was to compare the characteristics and outcomes of patients hospitalized in ICU for NSTI according to their antimicrobial therapy exposure > 24 h before surgery (called the exposed group) or not (called the unexposed group) before surgical microbiological sampling. We retrospectively included 100 consecutive patients admitted for severe NSTI. The exposed group consisted of 23(23%) patients, while 77(77%) patients belonged to the unexposed group. The demographic and underlying disease conditions were similar between the two groups. Microbiological cultures of surgical samples were positive in 84 patients and negative in 16 patients, including 3/23 (13%) patients and 13/77 (17%) patients in the exposed and unexposed groups, respectively (p = 0.70). The distribution of microorganisms was comparable between the two groups. The main antimicrobial regimens for empiric therapy were also similar, and the proportions of adequacy were comparable (n = 60 (84.5%) in the unexposed group vs. n = 19 (86.4%) in the exposed group, p = 0.482). ICU and hospital lengths of stay and mortality rates were similar between the two groups. In conclusion, in a population of severe ICU NSTI patients, antibiotic exposure before sampling did not impact either culture sample positivity or microbiological findings.

A clinically relevant sheep model of orthotopic heart transplantation 24 h after donor brainstem death.

BACKGROUND: Heart transplantation (HTx) from brainstem dead (BSD) donors is the gold-standard therapy for severe/end-stage cardiac disease, but is limited by a global donor heart shortage. Consequently, innovative solutions to increase donor heart availability and utilisation are rapidly expanding. Clinically relevant preclinical models are essential for evaluating interventions for human translation, yet few exist that accurately mimic all key HTx components, incorporating injuries beginning in the donor, through to the recipient. To enable future assessment of novel perfusion technologies in our research program, we thus aimed to develop a clinically relevant sheep model of HTx following 24 h of donor BSD. METHODS: BSD donors (vs. sham neurological injury, 4/group) were hemodynamically supported and monitored for 24 h, followed by heart preservation with cold static storage. Bicaval orthotopic HTx was performed in matched recipients, who were weaned from cardiopulmonary bypass (CPB), and monitored for 6 h. Donor and recipient blood were assayed for inflammatory and cardiac injury markers, and cardiac function was assessed using echocardiography. Repeated measurements between the two different groups during the study observation period were assessed by mixed ANOVA for repeated measures. RESULTS: Brainstem death caused an immediate catecholaminergic hemodynamic response (mean arterial pressure, p = 0.09), systemic inflammation (IL-6 - p = 0.025, IL-8 - p = 0.002) and cardiac injury (cardiac troponin I, p = 0.048), requiring vasopressor support (vasopressor dependency index, VDI, p = 0.023), with normalisation of biomarkers and physiology over 24 h. All hearts were weaned from CPB and monitored for 6 h post-HTx, except one (sham) recipient that died 2 h post-HTx. Hemodynamic (VDI - p = 0.592, heart rate - p = 0.747) and metabolic (blood lactate, p = 0.546) parameters post-HTx were comparable between groups, despite the observed physiological perturbations that occurred during donor BSD. All p values denote interaction among groups and time in the ANOVA for repeated measures. CONCLUSIONS: We have successfully developed an ovine HTx model following 24 h of donor BSD. After 6 h of critical care management post-HTx, there were no differences between groups, despite evident hemodynamic perturbations, systemic inflammation, and cardiac injury observed during donor BSD. This preclinical model provides a platform for critical assessment of injury development pre- and post-HTx, and novel therapeutic evaluation.

Tracheostomy in COVID-19 acute respiratory distress syndrome patients and follow-up: A parisian bicentric retrospective cohort.

BACKGROUND: Tracheostomy has been proposed as an option to help organize the healthcare system to face the unprecedented number of patients hospitalized for a COVID-19-related acute respiratory distress syndrome (ARDS) in intensive care units (ICU). It is, however, considered a particularly high-risk procedure for contamination. This paper aims to provide our experience in performing tracheostomies on COVID-19 critically ill patients during the pandemic and its long-term local complications. METHODS: We performed a retrospective analysis of prospectively collected data of patients tracheostomized for a COVID-19-related ARDS in two university hospitals in the Paris region between January 27th (date of first COVID-19 admission) and May 18th, 2020 (date of last tracheostomy performed). We focused on tracheostomy technique (percutaneous versus surgical), timing (early versus late) and late complications. RESULTS: Forty-eight tracheostomies were performed with an equal division between surgical and percutaneous techniques. There was no difference in patients' characteristics between surgical and percutaneous groups. Tracheostomy was performed after a median of 17 [12-22] days of mechanical ventilation (MV), with 10 patients in the "early" group (≤ day 10) and 38 patients in the "late" group (> day 10). Survivors required MV for a median of 32 [22-41] days and were ultimately decannulated with a median of 21 [15-34] days spent on cannula. Patients in the early group had shorter ICU and hospital stays (respectively 15 [12-19] versus 35 [25-47] days; p = 0.002, and 21 [16-28] versus 54 [35-72] days; p = 0.002) and spent less time on MV (respectively 17 [14-20] and 35 [27-43] days; p<0.001). Interestingly, patients in the percutaneous group had shorter hospital and rehabilitation center stays (respectively 44 [34-81] versus 92 [61-118] days; p = 0.012, and 24 [11-38] versus 45 [22-71] days; p = 0.045). Of the 30 (67%) patients examined by a head and neck surgeon, 17 (57%) had complications with unilateral laryngeal palsy (n = 5) being the most prevalent. CONCLUSIONS: Tracheostomy seems to be a safe procedure that could help ICU organization by delegating work to a separate team and favoring patient turnover by allowing faster transfer to step-down units. Following guidelines alone was found sufficient to prevent the risk of aerosolization and contamination of healthcare professionals.

Characterizing preclinical sub-phenotypic models of acute respiratory distress syndrome: An experimental ovine study.

The acute respiratory distress syndrome (ARDS) describes a heterogenous population of patients with acute severe respiratory failure. However, contemporary advances have begun to identify distinct sub-phenotypes that exist within its broader envelope. These sub-phenotypes have varied outcomes and respond differently to several previously studied interventions. A more precise understanding of their pathobiology and an ability to prospectively identify them, may allow for the development of precision therapies in ARDS. Historically, animal models have played a key role in translational research, although few studies have so far assessed either the ability of animal models to replicate these sub-phenotypes or investigated the presence of sub-phenotypes within animal models. Here, in three ovine models of ARDS, using combinations of oleic acid and intravenous, or intratracheal lipopolysaccharide, we investigated the presence of sub-phenotypes which qualitatively resemble those found in clinical cohorts. Principal Component Analysis and partitional clustering identified two clusters, differentiated by markers of shock, inflammation, and lung injury. This study provides a first exploration of ARDS phenotypes in preclinical models and suggests a methodology for investigating this phenomenon in future studies.

An innovative ovine model of severe cardiopulmonary failure supported by veno-arterial extracorporeal membrane oxygenation.

Refractory cardiogenic shock (CS) often requires veno-arterial extracorporeal membrane oxygenation (VA-ECMO) to sustain end-organ perfusion. Current animal models result in heterogenous cardiac injury and frequent episodes of refractory ventricular fibrillation. Thus, we aimed to develop an innovative, clinically relevant, and titratable model of severe cardiopulmonary failure. Six sheep (60 ± 6 kg) were anaesthetized and mechanically ventilated. VA-ECMO was commenced and CS was induced through intramyocardial injections of ethanol. Then, hypoxemic/hypercapnic pulmonary failure was achieved, through substantial decrease in ventilatory support. Echocardiography was used to compute left ventricular fractional area change (LVFAC) and cardiac Troponin I (cTnI) was quantified. After 5 h, the animals were euthanised and the heart was retrieved for histological evaluations. Ethanol (58 ± 23 mL) successfully induced CS in all animals. cTnI levels increased near 5000-fold. CS was confirmed by a drop in systolic blood pressure to 67 ± 14 mmHg, while lactate increased to 4.7 ± 0.9 mmol/L and LVFAC decreased to 16 ± 7%. Myocardial samples corroborated extensive cellular necrosis and inflammatory infiltrates. In conclusion, we present an innovative ovine model of severe cardiopulmonary failure in animals on VA-ECMO. This model could be essential to further characterize CS and develop future treatments.

Tracheostomy management in patients with severe acute respiratory distress syndrome receiving extracorporeal membrane oxygenation: an International Multicenter Retrospective Study.

BACKGROUND: Current practices regarding tracheostomy in patients treated with extracorporeal membrane oxygenation (ECMO) for acute respiratory distress syndrome are unknown. Our objectives were to assess the prevalence and the association between the timing of tracheostomy (during or after ECMO weaning) and related complications, sedative, and analgesic use. METHODS: International, multicenter, retrospective study in four large volume ECMO centers during a 9-year period. RESULTS: Of the 1,168 patients treated with ECMO for severe ARDS (age 48 ± 16 years, 76% male, SAPS II score 51 ± 18) during the enrollment period, 353 (30%) and 177 (15%) underwent tracheostomy placement during or after ECMO, respectively. Severe complications were uncommon in both groups. Local bleeding within 24 h of tracheostomy was four times more frequent during ECMO (25 vs 7% after ECMO, p < 0.01). Cumulative sedative consumption decreased more rapidly after the procedure with sedative doses almost negligible 48-72 h later, when tracheostomy was performed after ECMO decannulation (p < 0.01). A significantly increased level of consciousness was observed within 72 h after tracheostomy in the "after ECMO" group, whereas it was unchanged in the "during-ECMO" group. CONCLUSION: In contrast to patients undergoing tracheostomy after ECMO decannulation, tracheostomy during ECMO was neither associated with a decrease in sedation and analgesia levels nor with an increase in the level of consciousness. This finding together with a higher risk of local bleeding in the days following the procedure reinforces the need for a case-by-case discussion on the balance between risks and benefits of tracheotomy when performed during ECMO.

An Ovine Model of Hemorrhagic Shock and Resuscitation, to Assess Recovery of Tissue Oxygen Delivery and Oxygen Debt, and Inform Patient Blood Management.

BACKGROUND: Aggressive fluid or blood component transfusion for severe hemorrhagic shock may restore macrocirculatory parameters, but not always improve microcirculatory perfusion and tissue oxygen delivery. We established an ovine model of hemorrhagic shock to systematically assess tissue oxygen delivery and repayment of oxygen debt; appropriate outcomes to guide Patient Blood Management. METHODS: Female Dorset-cross sheep were anesthetized, intubated, and subjected to comprehensive macrohemodynamic, regional tissue oxygen saturation (StO2), sublingual capillary imaging, and arterial lactate monitoring confirmed by invasive organ-specific microvascular perfusion, oxygen pressure, and lactate/pyruvate levels in brain, kidney, liver, and skeletal muscle. Shock was induced by stepwise withdrawal of venous blood until MAP was 30 mm Hg, mixed venous oxygen saturation (SvO2) < 60%, and arterial lactate >4 mM. Resuscitation with PlasmaLyte® was dosed to achieve MAP > 65 mm Hg. RESULTS: Hemorrhage impacted primary outcomes between baseline and development of shock: MAP 89 ±â€Š5 to 31 ±â€Š5 mm Hg (P < 0.01), SvO2 70 ±â€Š7 to 23 ±â€Š8% (P < 0.05), cerebral regional tissue StO2 77 ±â€Š11 to 65 ±â€Š9% (P < 0.01), peripheral muscle StO2 66 ±â€Š8 to 16 ±â€Š9% (P < 0.01), arterial lactate 1.5 ±â€Š1.0 to 5.1 ±â€Š0.8 mM (P < 0.01), and base excess 1.1 ±â€Š2.2 to -3.6 ±â€Š1.7 mM (P < 0.05). Invasive organ-specific monitoring confirmed reduced tissue oxygen delivery; oxygen tension decreased and lactate increased in all tissues, but moderately in brain. Blood volume replacement with PlasmaLyte® improved primary outcome measures toward baseline, confirmed by organ-specific measures, despite hemoglobin reduced from baseline 10.8 ±â€Š1.2 to 5.9 ±â€Š1.1 g/dL post-resuscitation (P < 0.01). CONCLUSION: Non-invasive measures of tissue oxygen delivery and oxygen debt repayment are suitable outcomes to inform Patient Blood Management of hemorrhagic shock, translatable for pre-clinical assessment of novel resuscitation strategies.

SARS-CoV-2 vaccination efficacy on hospitalisation and variants.

We report data regarding three countries with similar healthcare systems which had three different vaccinal strategies between 1st of January and 10th of April 2021: rapid full vaccination (Israel), rapid first-dose vaccination (United Kingdom) and a delayed vaccination strategy (France).