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Purpose Septic shock is one of the leading causes of acute kidney injury. The mechanisms of this injury remain mostly unknown notably because of the lack of data on renal histological lesions in humans. Methods Kidney biopsy was performed immediately post-mortem in consecutive patients who died of septic shock. Comparisons were made with specimens from eight patients who died of trauma on scene and nine ICU patients that died of non-septic causes. Results Nineteen septic patients were included, 11 were male, and age was 72 ± 12 years. Anuria occurred in all patients 2.2 ± 1.4 days before death. Seven patients had disseminated intravascular coagulation. In all patients we observed (1) acute tubular lesions whose intensity correlated with blood lactate concentration; (2) intense infiltration by leukocytes, mainly monocytic, in glomeruli and interstitial capillaries as compared to controls; (3) presence of tubular cell apoptosis proved by the presence of apoptotic bodies (2.9% of tubular cells) significantly more frequently than in controls and confirmed by TUNEL and activated caspase-3 staining. Arteriolar/arterial thromboses were observed in only 4 of 19 patients, without any association with presence of disseminated intravascular coagulation. Conclusions Kidney lesions in septic shock go beyond those associated with simple acute tubular injury, notably capillary leukocytic infiltration and apoptosis. Vascular thrombosis, however, did not appear to play a major role in the majority of patients. The extent to which these lesions are specific to sepsis or are common to all multi-organ failure independent of its cause is yet to be elucidated.

Encephalitis caused by anti-N-methyl-d-aspartate receptor (NMDAR) antibodies is the leading cause of immune-mediated encephalitis. There are limited data on intensive care unit (ICU) management of these patients. To identify prognostic factors of good neurologic outcome in patients admitted to an ICU with anti-NMDAR encephalitis. This was an observational multicenter study of all consecutive adult patients diagnosed with anti-NMDAR encephalitis at the French National Reference Centre, admitted to an ICU between 2008 and 2014. The primary outcome was a good neurologic outcome at 6 months after ICU admission, defined by a modified Rankin Scale score of 0-2. Seventy-seven patients were included from 52 ICUs. First-line immunotherapy consisted of steroids (n = 61/74; 82%), intravenous immunoglobulins (n = 71/74; 96%), and plasmapheresis (n = 17/74; 23%). Forty-five (61%) patients received second-line immunotherapy (cyclophosphamide, rituximab, or both). At 6 months, 57% of patients had a good neurologic outcome. Independent factors of good neurologic outcome were early (≤8 d after ICU admission) immunotherapy (odds ratio, 16.16; 95% confidence interval, 3.32-78.64; for combined first-line immunotherapy with steroids and intravenous immunoglobulins vs. late immunotherapy), and a low white blood cell count on the first cerebrospinal examination (odds ratio, 9.83 for <5 vs. >50 cells/mm ; 95% confidence interval, 1.07-90.65). Presence of nonneurologic organ failures at ICU admission and occurrence of status epilepticus during ICU stay were not associated with neurologic outcome. The prognosis of adult patients with anti-NMDAR encephalitis requiring intensive care is good, especially when immunotherapy is initiated early, advocating for prompt diagnosis and early aggressive treatment.

Purpose Despite the benefits of mechanical ventilation, its use in critically ill patients is associated with complications and had led to the growth of noninvasive techniques. We assessed the effect of early intubation (first 8 h after vasopressor start) in septic shock patients, as compared to non-early intubated subjects (unexposed), regarding in-hospital mortality, intensive care and hospital length of stay. Methods This study involves secondary analysis of a multicenter prospective study. To adjust for baseline differences in potential confounders, propensity score matching was carried out. In-hospital mortality was analyzed in a time-to-event fashion, while length of stay was assessed as a median difference using bootstrapping. Results A total of 735 patients (137 intubated in the first 8 h) were evaluated. Propensity score matching identified 78 pairs with similar severity and characteristics on admission. Intubation was used in all patients in the early intubation group and in 27 (35%) subjects beyond 8 h in the unexposed group. Mortality occurred in 35 (45%) and in 26 (33%) subjects in the early intubation and unexposed groups (hazard ratio 1.44 95% CI 0.86–2.39, p  = 0.16). ICU and hospital length of stay were not different among groups [9 vs. 5 (95% CI 1 to 7) and 14 vs. 16 (95% CI − 7 to 8) days]. All sensitivity analyses confirmed the robustness of our findings. Conclusions An early approach to invasive mechanical ventilation did not improve outcomes in this matched cohort of patients. The limited number of patients included in these analyses out the total number included in the study may limit generalizability of these findings. Trial registration NCT02780466. Registered on May 19, 2016.

Background Recently, Objective Structured Clinical Examinations (OSCE) became an official evaluation modality for 6-year medical students in France. Before, standard examination modalities were: written progressive clinical cases (PCC), written critical reading of scientific articles (CRA), and internship evaluation (IE). The aim of this study was to assess the performances of 6-year medical students in their final faculty tests by comparing OSCE-exams with standard examination modalities. Methods This was a prospective observational study. We included all 6-year medical students in our university from 2020 to 2021. The endpoints were the scores obtained at the following final faculty tests during the 6 th year of medical studies: OSCE-training, OSCE-exams, written PCC, written CRA, and IE. All scores were compared in a paired-analysis. Results A total of 400 students were included in the study. No student was excluded in the final analysis. The mean scores obtained at the OSCE-exams were significantly different from those obtained at OSCE-training, PCC, CRA, and IE (12.6 ± 1.7, 11.7 ± 1.7, 13.4 ± 1.4, 13.2 ± 1.5, 14.7 ± 0.9, respectively; p  < 0.001). OSCE-exams scores were moderately and significantly correlated with OSCE-training and PCC (Spearman rho coefficient = 0.4, p  < 0.001); OSCE examination scores were lowly but significantly correlated with CRA and IE (Spearman rho coefficient = 0.3, p  < 0.001). OSCE-scores significantly increased after an OSCE training session. Conclusion In our faculty, 6-year medical students obtained lower scores at OSCE exams compared to other standard evaluation modalities. The correlation was weak to moderate but significant. These results suggest that OSCE are not redundant with the other evaluation modalities. Interestingly, a single OSCE training session led to an improvement in OSCE scores underlining the importance of a specific training.

Script Concordance Testing (SCT) is a method for clinical reasoning assessment in the field of health-care training. Our aim was to assess SCT acceptability and utility with a survey and an institutional prospective evaluation of students’ scores.With a user’s online survey, we collected the opinions and satisfaction data of all graduate students and teachers involved in the SCT setting. We performed a prospective analysis comparing the scores obtained with SCT to those obtained with the national standard evaluation modality. General opinions about SCT were mostly negative. Students tended to express more negative opinions and perceptions. There was a lower proportion of negative responses in the teachers’ satisfaction survey. The proportion of neutral responses was higher for teachers. There was a higher proportion of positive positions towards all questions among teachers. PCC scores significantly increased each year, but SCT scores increased only between the first and second tests. PCC scores were found significantly higher than SCT scores for the second and third tests. Medical students’ and teachers’ global opinion on SCT was negative. At the beginning SCT scores were found quite similar to PCC scores. There was a higher progression for PCC scores through time. Highlights • This study is the first to evaluate students and teachers’ opinions and perceptions about SCT and to compare the SCT grades to those obtained with standard examination modalities. • General students’ and teachers’ opinions about SCT were mostly negative. • There was a higher progression through time for students’ scores obtained with standard examination modalities than with SCT.

PurposeLittle is known on the incidence of discomfort during the end-of-life of intensive care unit (ICU) patients and the impact of sedation on such discomfort. The aim of this study was to assess the incidence of discomfort events according to levels of sedation.MethodsPost-hoc analysis of an observational prospective multicenter study comparing immediate extubation vs. terminal weaning for end-of-life in ICU patients. Discomforts including gasps, significant bronchial obstruction or high behavioural pain scale score, were prospectively assessed by nurses from mechanical ventilation withdrawal until death. Level of sedation was assessed using the Richmond Agitation–Sedation Scale (RASS) and deep sedation was considered for a RASS − 5. Psychological disorders in family members were assessed up until 12 months after the death.ResultsAmong the 450 patients included in the original study, 226 (50%) experienced discomfort after mechanical ventilation withdrawal. Patients with discomfort received lower doses of midazolam and equivalent morphine, and were less likely to have deep sedation than patients without discomfort (59% vs. 79%, p < 0.001). After multivariate logistic regression, extubation (as compared terminal weaning) was the only factor associated with discomfort, whereas deep sedation and administration of vasoactive drugs were two factors independently associated with no discomfort. Long-term evaluation of psychological disorders in family members of dead patients did not differ between those with discomfort and the others.ConclusionDiscomfort was frequent during end-of-life of ICU patients and was mainly associated with extubation and less profound sedation.

The objective of the study to is to determine the characteristics associated with endotracheal intubation in septic shock patients. This is a post hoc analysis of the database of the SEPSISPAM study, including patients with septic shock. Among the 776 patients, 633 (82%) were intubated within 12 hours of study inclusion (early intubation), 113 (15%) were never intubated, and 30 (4%) had delayed intubation. Intensive care units (ICUs) were classified according to frequency of early intubation: early intubation less than 80% of patients (lowest frequency: 7 ICUs, 254 patients), 80% to 90% (middle frequency: 5 ICUs, 170 patients), and greater than 90% (highest frequency: 6 ICUs, 297 patients). Type of ICU, pulmonary infection, lactate greater than 2 mmol/L, lower Pao2/fraction of inspired oxygen ratio, lower Glasgow score, and absence of immunosuppression were independently associated with early intubation. Patients never intubated had a lower initial severity and a low mortality rate. In comparison to patients intubated early, patients with delayed intubation had had fewer days alive without organ support by day 28. Intensive care units with the highest frequency of early intubation had a higher mortality rate in comparison to ICUs with middle frequency of early intubation. A nonsignificant increased mortality was observed in ICU with lowest frequency of early intubation. Practices regarding the place of endotracheal intubation in septic shock may impact outcome.

Background Near-peer tutoring appears to be an efficient approach for teaching clinical skills. However, the clinical experience gained in the form of student medical internships may offset any interest in such tutoring programme. We then investigated the long-term benefits of this programme. Methods This study was conducted in a medical school that experimented in near-peer tutoring for semiology intended for undergraduate medical students. Objective Structured Clinical Examinations and a written semiology test were used to assess students’ clinical skills immediately on its conclusion and repeated one and 2 years after the tutoring was completed. Results 116 students were evaluated initially (80 tutored and 36 untutored), 38 at 1 year (16 tutored and 22 untutored), 42 at 2 years (21 tutored and 21 untutored). In the global score for Objective Structured Clinical Examinations: at 1 year, the tutored group scored 14.0 ± 1.05 and the untutored group scored 11.3 ± 2.3 ( p  < 0.001), at 2 years, the tutored group scored 15.1 ± 1.5 and the untutored group scored 12.4 ± 2.2 ( p  < 0.001). We found a similar but smaller difference for the written semiology test. The difference for Objective Structured Clinical Examinations between tutored and untutored students vanished over time for cross-cutting skills. Conclusions Near-peer tutoring in semiology for undergraduate medical students led to better results that remained with the passing of time. Though internships do allow an improvement in the clinical skills of untutored students, they did not reach the level of tutored students.

[...]no international or local guidelines exist regarding prescription of these tests. [...]in the absence of any recommendation to follow, we do not think that conducting the study altered significantly physicians practice.

Purpura fulminans in adults is a rare but devastating disease. Its pathophysiology is not well known. To understand the pathophysiology of skin lesions in purpura fulminans, the interplay between circulating blood and vascular alterations was assessed. Prospective multicenter study in four intensive care units. Patients with severe sepsis without skin lesions were recruited as control subjects. Twenty patients with severe sepsis and purpura fulminans were recruited for blood sampling, and skin biopsy was performed in deceased patients. High severity of disease and mortality rates (80%) was observed. Skin biopsies in purpura fulminans lesions revealed thrombosis and extensive vascular damage: vascular congestion and dilation, endothelial necrosis, alteration of markers of endothelial integrity (CD31) and of the protein C pathway receptors (endothelial protein C receptor, thrombomodulin). Elevated plasminogen activating inhibitor-1 mRNA was also observed. Comparison with control patients showed that these lesions were specific to purpura fulminans. By contrast, no difference was observed for blood hemostasis parameters, including soluble thrombomodulin, activated protein C, and disseminated intravascular coagulation markers. Bacterial presence at the vascular wall was observed specifically in areas of vascular damage in eight of nine patients tested (including patients with Streptococcus pneumoniae, Neisseria meningitidis, Escherichia coli, and Pseudomonas aeruginosa infection). Thrombi and extensive vascular damage with multifaceted prothrombotic local imbalance are characteristics of purpura fulminans. A \"vascular wall infection\" hypothesis, responsible for endothelial damage and subsequent skin lesions, can be put forward.