Objectives To describe stress, coping behaviours, anxiety, psychological support and benzodiazepine use among French final-year medical students sitting a high-stakes national ranking examination and to explore how these patterns relate to exam ranking when interpreted through transactional stress and coping and ‘coping reservoir’ models. Design Cross-sectional questionnaire survey. Setting Single university medical faculty in France; final-year students sitting the national Épreuves Dématérialisées Nationales (EDN) and ‘national Objective Structured Clinical Examination (nOSCE)’ clinical examination. Participants All 387 sixth-year students present for the 2025 nOSCE were invited; 192 (50%) completed the questionnaire (69% women; median age 25 years). Inclusion: registered for the national exam and attending nOSCE; exclusion: non-attendance or incomplete questionnaire. Interventions None. Primary and secondary outcome measures Primary outcomes were self-rated stress for EDN and nOSCE and State-Trait Anxiety Inventory-Y (STAI-Y) state and trait anxiety scores. Secondary outcomes included stress management behaviours, psychological/psychiatric follow-up, benzodiazepine and other psychotropic use and final national ranking. Results 92% of respondents reported that stress impacted their daily life, particularly attention (83%), sleep (79%) and learning capacity (64%). Overall, 32% had consulted a psychologist/psychiatrist and 15% used benzodiazepines. Most reported regular sport (86%; ≥2 sports 69%) and breathing exercises (61%). Median nOSCE stress was 8/10; median STAI-Y state and trait scores were 45 and 46. Comparing very low versus high/very high trait-anxiety subgroups, ranking did not differ significantly, but low-anxiety students reported more sport (p=0.04), less benzodiazepine use (1/24 vs 10/37; p=0.003) and far less psychological follow-up (1/24 vs 19/46; p<0.0001). Self-reported coping strategies were not associated with better ranking. Conclusions Final-year medical students preparing for a high-stakes national ranking examination report pervasive stress, substantial functional impairment and frequent professional and pharmacological coping, with only limited linkage between anxiety and performance. Within transactional and coping reservoir frameworks, these results highlight the need for reflection on structural assessment practices and for longitudinal institutional strategies to protect learner well-being.

Background:Acute kidney injury (AKI) requiring continuous renal replacement therapy (CRRT) is frequent in the intensive care unit (ICU). While the timing of initiation has been extensively studied, discontinuation remains poorly defined. Current guidelines provide only vague recommendations, and CRRT liberation is mainly guided by clinical judgment. Methods:We aimed to compare declared and real CRRT weaning practices among intensivists in septic AKI.We conducted one study with two complementary investigations. Phase 1 was a nationwide survey distributed to 230 French ICUs that explored physician experience, weaning criteria, fluid balance management, urine output thresholds, and urinary biomarker use. A total of 243 intensivists from 87 ICUs responded. Phase 2 was a multicentre retrospective cohort study describing real-world management across 22 ICUs of patients with septic AKI who initiated and were subsequently weaned from CRRT. Weaning was defined as the first discontinuation of CRRT with the intent to stop, regardless of later resumption. We collected clinical, hemodynamic, renal, and fluid data over the 5 days before Day 0, the weaning day. Results:In survey phase, 93% of respondents cited urine output as the main criterion for discontinuation, with a mean reported threshold of 612 ± 328 mL/day; 74% reassessed daily, and only 3% reported using a protocol. In the retrospective cohort phase (n = 116), markedly lower urine outputs were observed at weaning (median 275 mL [30-967] on D0, 122 mL [17-562] on D-1). On weaning day, 52% of patients were still on norepinephrine (median dose 0.22 μg/kg/min, bitartrate), 72% had a positive cumulative fluid balance (median +5 L), and diuretics were prescribed in 25% of patients. In unadjusted comparisons, patients with successful weaning (63%) had higher urine output at discontinuation and more frequent diuretic use, whereas vasopressor support and fluid balance substantially overlapped between groups. In multivariable analysis, only persistent anuria as the indication for CRRT initiation remained independently associated with weaning failure. Conclusions:This combined analysis highlights a discrepancy between reported weaning practices and observed bedside management at the centre level. Despite declared reliance on urine output, hemodynamic stability, and decongestion, CRRT is often discontinued under oliguria, residual vasopressor use, and persistent fluid overload. The absence of standardized protocols underscores the need for validated composite readiness criteria that integrate urine output, vasopressor dependency, fluid status, and, possibly, urinary biomarkers.

The weaning of critical care patients with acute kidney injury (AKI) from renal replacement therapy (RRT) lacks predictive criteria. The urinary urea excretion index (UUEI) based on the urine urea concentration and diuresis may be a relevant prognostic criterion. The aim of this study was to assess the value of utilising a UUEI-based weaning protocol from a RRT catheter. This was a multicentre before-after study including patients with non-obstructive AKI requiring RRT during their intensive care unit (ICU) stay. A before cohort (2013–2015) was compared to an after cohort (2017–2019) in the interval of which a UUEI-based weaning protocol was implemented. In the after cohort, as soon as the UUEI exceeded 1.35 mmol/kg/24 h, physicians were encouraged to stop RRT and withdraw the catheter, whereas in the before cohort the catheter was withdrawn at the physician’s discretion. The primary outcome was the number of RRT catheter-free days on day 28 after initiating RRT. In total, 179 and 130 patients were included in the before and after cohorts, respectively. The median numbers of catheter-free days in the before and after cohorts on day 28 were 13.0 (IQR 0.0–21.0) vs. 16.5 (IQR 4.3–24.0), respectively (p = 0.02). The adjusted rate ratio for the number of catheter-free days over the number of days at risk was 1.11 (95

Background The benefit–risk balance and optimal timing of surgery for severe infective endocarditis (IE) with ischemic or hemorrhagic strokes is unknown. The study aim was to compare the neurological outcome between patients receiving surgery or not. Methods In a prospective register-based multicenter ICU study, patients were included if they met the following criteria: (i) left-sided IE with an indication for heart surgery; (ii) with cerebral complications documented by cerebral imaging before cardiac surgery; (iii) with Sequential Organ Failure Assessment score ≥ 3. Exclusion criteria were isolated right-sided IE, in-hospital acquired IE and patients with cerebral complications only after cardiac surgery. In the primary analysis, the prognostic value of surgery in term of disability at 6 month was assessed by using a propensity score-adjusted logistic regression. Results 192 patients were included including ischemic stroke (74.5%) and hemorrhagic lesion (15.6%): 67 (35%) had medical treatment and 125 (65%) cardiac surgery. In the propensity score-adjusted logistic regression, a favorable 6-month neurological outcome was associated with surgery (odds ratio 13.8 (95% CI 6.2–33.7). The 1-year mortality was strongly reduced with surgery in the fixed-effect propensity-adjusted Cox model (hazard ratio 0.18; 95% CI 0.11–0.27; p < 0.001). These effects remained whether the patients received delayed surgery ( n = 62/125) or not and whether they were deeply comatose (Glasgow Coma Scale ≤ 10) or not. Conclusions In critically ill IE patients with an indication for surgery and previous cerebral events, a better propensity-adjusted neurological outcome was associated with surgery compared with medical treatment.

Background Acute kidney injury (AKI) in intensive care unit (ICU) patients with severe COVID-19 is common (> 50%). A specific inflammatory process has been suggested in the pathogenesis of AKI, which could be improved by dexamethasone (DXM). In a small monocenter study ( n = 100 patients), we reported a potential protective effect of DXM on the risk of AKI. This study aimed to investigate the preventive impact of DXM on AKI in a multicenter study of patients with severe COVID-19. Methods We conducted a multicenter study in three French ICUs from March 2020 to August 2021. All patients admitted to ICU for severe COVID-19 were included. Individuals with preexistent AKI or DXM administration before admission to ICU were excluded. While never used during the first wave, DXM was used subsequently at ICU entry, providing two treatment groups. Multivariate Cause-specific Cox models taking into account changes in ICU practices over time, were utilized to determine the association between DXM and occurrence of AKI. Results Seven hundred and ninety-eight patients were included. Mean age was 62.6 ± 12.1 years, 402/798 (50%) patients had hypertension, and 46/798 (6%) had previous chronic kidney disease. Median SOFA was 4 [3–6] and 420/798 (53%) required invasive mechanical ventilation. ICU mortality was 208/798 (26%). AKI was present in 598/798 (75%) patients: 266/598 (38%), 163/598 (27%), and 210/598 (35%) had, respectively, AKI KDIGO 1, 2, 3, and 61/598 (10%) patients required renal replacement therapy. Patients receiving DXM had a significantly decreased hazard of AKI occurrence compared to patients without DXM (HR 0.67; 95CI 0.55–0.81). These results were consistent in analyses that (1) excluded patients with DXM administration to AKI onset delay of less than 12 h, (2) incorporating the different ‘waves’ of the COVID-19 pandemic. Conclusions DXM was associated with a decrease in the risk of AKI in severe COVID-19 patients admitted to ICU. This supports the hypothesis that the inflammatory injury of AKI may be preventable.

OBJECTIVE:We hypothesized that the use of mechanical insufflation-exsufflation can reduce the incidence of acute respiratory failure within the 48-hour post-extubation period in intensive care unit-acquired weakness patients.METHODS:This was a prospective randomized controlled open-label trial. Patients diagnosed with intensive care unit-acquired weakness were consecutively enrolled based on a Medical Research Council score ≤ 48/60. The patients randomly received two daily sessions; in the control group, conventional chest physiotherapy was performed, while in the intervention group, chest physiotherapy was associated with mechanical insufflation-exsufflation. The incidence of acute respiratory failure within 48 hours of extubation was evaluated. Similarly, the reintubation rate, intensive care unit length of stay, mortality at 28 days, and survival probability at 90 days were assessed. The study was stopped after futility results in the interim analysis.RESULTS:We included 122 consecutive patients (n = 61 per group). There was no significant difference in the incidence of acute respiratory failure between treatments (11.5% control group versus 16.4%, intervention group; p = 0.60), the need for reintubation (3.6% versus 10.7%; p = 0.27), mean length of stay (3 versus 4 days; p = 0.33), mortality at Day 28 (9.8% versus 15.0%; p = 0.42), or survival probability at Day 90 (21.3% versus 28.3%; p = 0.41).CONCLUSION:Mechanical insufflation-exsufflation combined with chest physiotherapy seems to have no impact in preventing postextubation acute respiratory failure in intensive care unit-acquired weakness patients. Similarly, mortality and survival probability were similar in both groups. Nevertheless, given the early termination of the trial, further clinical investigation is strongly recommended.CLINICAL TRIALS REGISTER:NCT01931228.

Abstract Background The rise in antimicrobial resistance is a global threat responsible for about 33,000 deaths in 2015 with a particular concern for extended-spectrum beta-lactamase-producing Enterobacterales (ESBL-E) and has led to a major increase in the use of carbapenems, last-resort antibiotics. Methods In this retrospective propensity-weighted multicenter observational study conducted in 11 ICUs, the purpose was to assess the efficacy of non carbapenem regimen (piperacillin–tazobactam (PTZ) + aminoglycosides or 3rd-generation cephalosporin (3GC) + aminoglycosides) as empiric therapy in comparison with carbapenem in extended-spectrum β-lactamase-producing Enterobacterales (ESBL-E) urinary septic shock. The primary outcome was Day-30 mortality. Results Among 156 patients included in this study, 69 received a carbapenem and 87 received non carbapenem antibiotics as empiric treatment. Baseline clinical characteristics were similar between the two groups. Patients who received carbapenem had similar Day-30 mortality (10/69 (15%) vs 6/87 (7%), OR = 1.99 [0.55; 5.34] p = 0.16), illness severity, resolution of septic shock, and ESBL-E infection recurrence rates than patients who received an empiric non carbapenem therapy. The rates of secondary infection with C. difficile were comparable. Conclusions In ESBL-E urinary septic shock, empiric treatment with a non carbapenem regimen, including systematically aminoglycosides, was not associated with higher mortality, compared to a carbapenem regimen.

Ventilator-associated pneumonia (VAP) is the most frequent nosocomial infection in critically ill-ventilated patients. Oropharyngeal and lung microbiota have been demonstrated to be associated with VAP occurrence, but the involvement of gut microbiota has not been investigated so far. Therefore, the aim of this study is to compare the composition of the gut microbiota between patients who subsequently develop VAP and those who do not. A rectal swab was performed at admission of every consecutive patient into the intensive care unit (ICU) from October 2019 to March 2020. After DNA extraction, V3-V4 and internal transcribed spacer 2 regions deep-sequencing was performed on MiSeq sequencer (Illumina) and data were analyzed using Divisive Amplicon Denoising Algorithm 2 (DADA2) pipeline. Among 255 patients screened, 42 (16%) patients with invasive mechanical ventilation for more than 48 h were included, 18 (43%) with definite VAP and 24 without (57%). Patients who later developed VAP had similar gut bacteriobiota and mycobiota alpha-diversities compared to those who did not develop VAP. However, gut mycobiota was dissimilar (beta-diversity) between these two groups. The presence of Megasphaera massiliensis was associated with the absence of VAP occurrence, whereas the presence of the fungal genus Alternaria sp. was associated with the occurrence of VAP. The composition of the gut microbiota, but not alpha-diversity, differs between critically ill patients who subsequently develop VAP and those who do not. This study encourages large multicenter cohort studies investigating the role of gut-lung axis and oropharyngeal colonization in the development of VAP in ICU patients. Trial registration number: NCT04131569, date of registration: 18 October 2019. IMPORTANCE The composition of the gut microbiota, but not alpha-diversity, differs between critically ill patients who subsequently develop ventilator-associated pneumonia (VAP) and those who do not. Investigating gut microbiota composition could help to tailor probiotics to provide protection against VAP.

BACKGROUND:Patients suffering from acute kidney injury(AKI) in the intensive care unit (ICU) can have various renal trajectories and outcomes. Aims were to assess the various clinical trajectories after AKI in the ICU and to determine risk factors for developing chronic kidney disease (CKD). METHODS:We conducted a prospective 5-year follow-up study in a medical ICU at Bordeaux University Hospital (France). The patients who received invasive mechanical ventilation, catecholamine infusion or both and developed an AKI from September 2013 to May 2015 were included. In the Cox analysis, the violation of the proportional hazard assumption for AKD was handled using appropriate interaction terms with time, resulting in a time-dependent hazard ratio (HR). RESULTS:A total of 232 patients were enrolled, with an age of 62 ± 16 years and a median follow-up of 52 days (interquartile range 6-1553). On day 7, 109/232 (47%) patients progressed to acute kidney disease (AKD) and 66/232 (28%) recovered. A linear trajectory (AKI, AKD to CKD) was followed by 44/63 (70%) of the CKD patients. The cumulative incidence of CKD was 30% [95% confidence interval (CI) 24-36] at the 5-year follow-up. In a multivariable Cox model, in the 6 months following AKI, the HR for CKD was higher in AKD patients [HR 29.2 (95% CI 8.5-100.7); P < 0.0001). After 6 months, the HR for CKD was 2.2 (95% CI 0.6-7.9; P = 0.21; n = 172 patients). CONCLUSION:There were several clinical trajectories of kidney disease after ICU-acquired AKI. CKD risk was higher in AKD patients only in the first 6 months. Lack of renal recovery rather than AKD per se was associated with the risk of CKD.

The increase in worldwide travel is making imported malaria a growing health concern in non-endemic countries. Most data on the pathophysiology of malaria come from endemic areas. Little is known about cytokine profiles during imported malaria. This study aimed at deciphering the relationship between cytokine host response and malaria severity among imported cases in France. This study reports cytokine profiles in adults with Plasmodium falciparum malaria included in the PALUREA prospective study conducted between 2006 and 2010. The patients were classified as having uncomplicated malaria (UM) or severe malaria (SM), with this last further categorized as very severe malaria (VSM) or less severe malaria (LSM). At hospital admission, eight blood cytokines were assayed in duplicate using Luminex ® technology: interleukin (IL)-1α, IL-1β, IL-2, IL-4, IL-10, tumor necrosis factor (TNF)α, interferon (IFN)γ, and macrophage migration inhibitory factor (MIF). These assays were repeated on days 1 and 2 in the SM group. Of the 278 patients, 134 had UM and 144 SM. At hospital admission, over half the patients had undetectable levels of IL-1α, IL-1β, IL-2, IL-4, IFNγ, and TNFα, while IL-10 and MIF were significantly higher in the SM vs. the UM group. Higher IL-10 was significantly associated with higher parasitemia (R = 0.32 [0.16–0.46]; P = 0.0001). In the SM group, IL-10 elevation persisting from admission to day 2 was significantly associated with subsequent nosocomial infection. Of eight tested cytokines, only MIF and IL-10 were associated with disease severity in adults with imported P. falciparum malaria. At admission, many patients had undetectable cytokine levels, suggesting that circulating cytokine assays may not be helpful as part of the routine evaluation of adults with imported malaria. Persisting high IL-10 concentration was associated with subsequent nosocomial infection, suggesting its possible interest in immune monitoring of most severe patients.

Acute respiratory distress syndrome (ARDS) is responsible for 400,000 deaths annually worldwide. Few improvements have been made despite five decades of research, partially because ARDS is a highly heterogeneous syndrome including various types of aetiologies. Lower airway microbiota is involved in chronic inflammatory diseases and recent data suggest that it could also play a role in ARDS. Nevertheless, whether the lower airway microbiota composition varies between the aetiologies of ARDS remain unknown. The aim of this study is to compare lower airway microbiota composition between ARDS aetiologies, i.e. pulmonary ARDS due to influenza, SARS-CoV-2 or bacterial infection. Consecutive ARDS patients according to Berlin’s classification requiring invasive ventilation with PCR-confirmed influenza or SARS-CoV-2 infections and bacterial infections (> 105 CFU/mL on endotracheal aspirate) were included. Endotracheal aspirate was collected at admission, V3-V4 and ITS2 regions amplified by PCR, deep-sequencing performed on MiSeq sequencer (Illumina®) and data analysed using DADA2 pipeline. Fifty-three patients were included, 24 COVID-19, 18 influenza, and 11 bacterial CAP-related ARDS. The lower airway bacteriobiota and mycobiota compositions (β-diversity) were dissimilar between the three groups (p = 0.05 and p = 0.01, respectively). The bacterial α-diversity was significantly lower in the bacterial CAP-related ARDS group compared to the COVID-19 ARDS group (p = 0.04). In contrast, influenza-related ARDS patients had higher lung mycobiota α-diversity than the COVID-19-related ARDS (p = 0 < 01). Composition of lower airway microbiota (both microbiota and mycobiota) differs between influenza, COVID-19 and bacterial CAP-related ARDS. Future studies investigating the role of lung microbiota in ARDS pathophysiology should take aetiology into account.

Background The worldwide dissemination of extended spectrum beta-lactamase producing Enterobacteriales (ESBL-E) is of major concern. Microbiota may play a role in the host resistance to colonization with ESBL-E, but the underlying mechanisms remain unknown. We aimed to compare the gut microbiota composition between ESBL-producing E. coli or K. pneumoniae carriers and ESBL-E non-carriers according to the bacterial species. Results Among 255 patients included, 11 (4,3%) were colonized with ESBL-producing E. coli and 6 (2,4%) with ESBL-producing K. pneumoniae, which were compared with age- and sex-matched ESBL-E non carriers. While no significant differences were found between ESBL-producing E. coli carriers and non-carriers, gut bacteriobiota α-diversity was decreased in ESBL- K. pneumoniae faecal carriers compared both with non-carriers ( p = 0.05), and with ESBL-producing E. coli carriers. The presence of Sellimonas intestinalis was associated with the absence of ESBL-producing E. coli fecal carriage. Campylobacter ureolyticus , Campylobacter hominis , bacteria belonging to Clostridium cluster XI and Saccharomyces sp. were associated with the absence of ESBL-producing K. pneumoniae faecal carriage. Conclusions The composition of the gut microbiota differs between ESBL-producing E. coli and K. pneumoniae faecal carriers suggesting that microbial species should be taken into account when investigating the role of gut microbiota in resistance to gut colonization with ESBL-E. Trial registration number : NCT04131569, date of registration: October 18, 2019.

Chronic obstructive pulmonary disease (COPD) affects more than 200 million people worldwide. The chronic course of COPD is frequently worsened by acute exacerbations (AECOPD). Mortality in patients hospitalized for severe AECOPD remains dramatically high, and the underlying mechanisms are poorly understood. Lung microbiota is associated with COPD outcomes in nonsevere AECOPD, but no study specifically investigated severe AECOPD patients. The aim of this study is thus to compare lung microbiota composition between severe AECOPD survivors and nonsurvivors. Induced sputum or endotracheal aspirate was collected at admission from every consecutive severe AECOPD patient. After DNA extraction, the V3-V4 and ITS2 regions were amplified by PCR. Deep-sequencing was performed on a MiSeq sequencer (Illumina); the data were analyzed using DADA2 pipeline. Among 47 patients admitted for severe AECOPD, 25 (53%) with samples of sufficient quality were included: 21 of 25 (84%) survivors and 4 of 25 (16%) nonsurvivors. AECOPD nonsurvivors had lower α-diversities indices than survivors for lung mycobiota but not for lung bacteriobiota. Similar results were demonstrated comparing patients receiving invasive mechanical ventilation (n = 13 [52%]) with those receiving only noninvasive ventilation (n = 12 [48%]). Previous systemic antimicrobial therapy and long-term inhaled corticosteroid therapy could alter the lung microbiota composition in severe AECOPD patients. In acidemic AECOPD, lower lung mycobiota α-diversity is linked to the severity of the exacerbation, assessed by mortality and the requirement for invasive mechanical ventilation, whereas lung bacteriobiota α-diversity is not. This study encourages a multicenter cohort study investigating the role of lung microbiota, especially fungal kingdom, in severe AECOPD. IMPORTANCE In AECOPD with acidemia, more severe patients-i.e., nonsurvivors and patients requiring invasive mechanical ventilation-have lower lung mycobiota α-diversity than survivors and patients receiving only noninvasive ventilation, respectively. This study encourages a large multicenter cohort study investigating the role of lung microbiota in severe AECOPD and urges investigation of the role of the fungal kingdom in severe AECOPD.

OBJECTIVE: We hypothesized that the use of mechanical insufflation-exsufflation can reduce the incidence of acute respiratory failure within the 48-hour post-extubation period in intensive care unit-acquired weakness patients. METHODS: This was a prospective randomized controlled open-label trial. Patients diagnosed with intensive care unit-acquired weakness were consecutively enrolled based on a Medical Research Council score ≤ 48/60. The patients randomly received two daily sessions; in the control group, conventional chest physiotherapy was performed, while in the intervention group, chest physiotherapy was associated with mechanical insufflation-exsufflation. The incidence of acute respiratory failure within 48 hours of extubation was evaluated. Similarly, the reintubation rate, intensive care unit length of stay, mortality at 28 days, and survival probability at 90 days were assessed. The study was stopped after futility results in the interim analysis. RESULTS: We included 122 consecutive patients (n = 61 per group). There was no significant difference in the incidence of acute respiratory failure between treatments (11.5% control group versus 16.4%, intervention group; p = 0.60), the need for reintubation (3.6% versus 10.7%; p = 0.27), mean length of stay (3 versus 4 days; p = 0.33), mortality at Day 28 (9.8% versus 15.0%; p = 0.42), or survival probability at Day 90 (21.3% versus 28.3%; p = 0.41). CONCLUSION: Mechanical insufflation-exsufflation combined with chest physiotherapy seems to have no impact in preventing postextubation acute respiratory failure in intensive care unit-acquired weakness patients. Similarly, mortality and survival probability were similar in both groups. Nevertheless, given the early termination of the trial, further clinical investigation is strongly recommended. CLINICAL TRIALS REGISTER: NCT 01931228

Abstract Background Acute kidney injury (AKI) requiring renal replacement therapy (RRT) is a serious complication in the ICU that results in increased mortality and risk of chronic kidney disease (CKD). Some studies suggest RRT modality may have an impact on long-term renal recovery after AKI. However, other predictive factors of severe long-term CKD in ICU patients with AKI requiring RRT are unknown. Methods We performed an ancillary study of the multicenter ELVIS trial in the population with AKI requiring RRT. Patients alive 3 months after RRT initiation were eligible. Serum creatinine levels available at 3, 6 and 12 months and 3 and 5 years were recorded. CKD stage was determined according to the glomerular filtration rate as estimated by the CKD-EPI formula. At each timepoint, two groups of patients were compared, a no/mild CKD group with normal or mildly to moderately decreased renal function (stages 1, 2 and 3 of the international classification) and a severe CKD group (stages 4 and 5). Our objective was to identify predictive factors of severe long-term CKD. Results Of the 287 eligible patients, 183 had follow-up at 3 months, 136 (74.3%) from the no/mild CKD group and 47 (25.7%) from the severe CKD group, and 122 patients at 5 years comprising 96 (78.7%) from the no/mild CKD group and 26 (21.3%) from the severe CKD group. Multivariate analysis showed that a long RRT period was associated with severe CKD up to 12 months (ORM12 = 1.03 95% CI [1.02–1.05] per day) and that a high SOFA score at the initiation of RRT was not associated with severe CKD up to 5 years (ORM60 = 0.85 95% CI [0.77–0.93] per point). Conclusion Severe long-term CKD was found in 21% of ICU survivors who underwent RRT for AKI. The duration of the RRT in AKI patients was identified as a new predictive factor for severe long-term CKD. This finding should be taken into consideration in future studies on the prognosis of ICU patients with AKI requiring RRT. Trial registration ELVIS trial was registered with ClinicalTrials.gov, number: NCT00875069 (June 16, 2014), and this ancillary study was registered with ClinicalTrials.gov, number: NCT03302624 (October 6, 2017).

L’insuffisance rénale aiguë (IRA) chez les patients atteints de COVID-19 en réanimation est fréquente (> 50 %). Un processus inflammatoire spécifique avait été suggéré dans la physiopathologie de l’IRA. L’objectif de cette étude était d’examiner l’impact de la DXM sur l’incidence de l’IRA induite par la COVID-19. Étude prospective multicentrique dans deux unités de soins intensifs françaises du 1er mars 2020 au 21 août 2021. Tous les patients admis pour un COVID-19 sévère ont été inclus. La DXM a été exclusivement utilisée à partir de la deuxième vague. L’insuffisance rénale aiguë a été définie selon la classification KDIGO. Les patients ayant eu de la DXM avant ou le jour de l’IRA ont été exclus de l’analyse. Au total, 1014 patients ont été inclus. La DXM a été administrée chez 635/1014 (63 %). L’âge moyen était de 63 ± 12 ans, 520/1014 ; 75/1014 (7 %) souffraient d’une maladie rénale chronique (MRC) antérieure et 385/1014 (38 %) ont eu besoin d’une ventilation mécanique invasive (MV) dans les 24 premières heures. La mortalité en soins intensifs était de 264/1014 (26 %). L’insuffisance rénale aiguë était présente chez 735/1014 (73 %) patients : 284/735 (39 %), 195/735 (27 %) et 256/735 (35 %) présentaient respectivement une insuffisance rénale aiguë KDIGO 1, 2 et 3 et 88/735 (12 %) ont eu besoin d’épuration extra-rénale. Parmi les 635 patients qui ont reçu du DXM, l’utilisation de la DXM (OR = 0,26 [0,17–0,40]) et du tocilizumab (OR = 0,16 [0,03–0,74]) était indépendamment associée à une diminution du risque d’IRA (Tableau 1). Dans notre étude, l’exposition au DXM et au tocilizumab était indépendamment associée à une diminution de l’incidence de l’IRA. Ces résultats soutiennent l’hypothèse que l’IRA induite par le COVID-19 est partiellement secondaire à un processus inflammatoire.

Thrombotic microangiopathy (TMA) gathers consumptive thrombocytopenia, mechanical haemolytic anemia, and organ damage. Hemolytic uremic syndromes (HUS) are historically classified as primary or secondary to another disease once thrombotic thrombocytopenic purpura (TTP), Shiga-toxin HUS, and cobalamin C-related HUS have been ruled out. Complement genetics studies reinforced the link between complement dysregulation and primary HUS, contributing to reclassifying some pregnancy- and/or post-partum-associated HUS and to revealing complement involvement in severe and/or refractory hypertensive emergencies. By contrast, no firm evidence allows a plausible association to be drawn between complement dysregulation and Shiga-toxin HUS or other secondary HUS. Nevertheless, rare complement gene variants are prevalent in healthy individuals, thus providing an indication that an investigation into complement dysregulation should be carefully balanced and that the results should be cautiously interpreted with the help of a trained geneticist. Several authors have suggested reclassifying HUS in two entities, regardless of they are complement-mediated or not, since the use of eculizumab, an anti-C5 antibody, dramatically lowers the proportion of patients who die or suffer from end-stage renal disease within the year following diagnosis. Safety and the ideal timing of eculizumab discontinuation is currently under investigation, and the long-term consequences of HUS should be closely monitored over time once patients exit emergency departments.

BackgroundThe Solidarity trial among COVID-19 inpatients has previously reported interim mortality analyses for four repurposed antiviral drugs. Lopinavir, hydroxychloroquine, and interferon (IFN)-β1a were discontinued for futility but randomisation to remdesivir continued. Here, we report the final results of Solidarity and meta-analyses of mortality in all relevant trials to date.MethodsSolidarity enrolled consenting adults (aged ≥18 years) recently hospitalised with, in the view of their doctor, definite COVID-19 and no contraindication to any of the study drugs, regardless of any other patient characteristics. Participants were randomly allocated, in equal proportions between the locally available options, to receive whichever of the four study drugs (lopinavir, hydroxychloroquine, IFN-β1a, or remdesivir) were locally available at that time or no study drug (controls). All patients also received the local standard of care. No placebos were given. The protocol-specified primary endpoint was in-hospital mortality, subdivided by disease severity. Secondary endpoints were progression to ventilation if not already ventilated, and time-to-discharge from hospital. Final log-rank and Kaplan-Meier analyses are presented for remdesivir, and are appended for all four study drugs. Meta-analyses give weighted averages of the mortality findings in this and all other randomised trials of these drugs among hospital inpatients. Solidarity is registered with ISRCTN, ISRCTN83971151, and ClinicalTrials.gov, NCT04315948.FindingsBetween March 22, 2020, and Jan 29, 2021, 14 304 potentially eligible patients were recruited from 454 hospitals in 35 countries in all six WHO regions. After the exclusion of 83 (0·6%) patients with a refuted COVID-19 diagnosis or encrypted consent not entered into the database, Solidarity enrolled 14 221 patients, including 8275 randomly allocated (1:1) either to remdesivir (ten daily infusions, unless discharged earlier) or to its control (allocated no study drug although remdesivir was locally available). Compliance was high in both groups. Overall, 602 (14·5%) of 4146 patients assigned to remdesivir died versus 643 (15·6%) of 4129 assigned to control (mortality rate ratio [RR] 0·91 [95% CI 0·82–1·02], p=0·12). Of those already ventilated, 151 (42·1%) of 359 assigned to remdesivir died versus 134 (38·6%) of 347 assigned to control (RR 1·13 [0·89–1·42], p=0·32). Of those not ventilated but on oxygen, 14·6% assigned to remdesivir died versus 16·3% assigned to control (RR 0·87 [0·76–0·99], p=0·03). Of 1730 not on oxygen initially, 2·9% assigned to remdesivir died versus 3·8% assigned to control (RR 0·76 [0·46–1·28], p=0·30). Combining all those not ventilated initially, 11·9% assigned to remdesivir died versus 13·5% assigned to control (RR 0·86 [0·76–0·98], p=0·02) and 14·1% versus 15·7% progressed to ventilation (RR 0·88 [0·77–1·00], p=0·04). The non-prespecified composite outcome of death or progression to ventilation occurred in 19·6% assigned to remdesivir versus 22·5% assigned to control (RR 0·84 [0·75–0·93], p=0·001). Allocation to daily remdesivir infusions (vs open-label control) delayed discharge by about 1 day during the 10-day treatment period. A meta-analysis of mortality in all randomised trials of remdesivir versus no remdesivir yielded similar findings.InterpretationRemdesivir has no significant effect on patients with COVID-19 who are already being ventilated. Among other hospitalised patients, it has a small effect against death or progression to ventilation (or both).FundingWHO.