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Background and Aims: Utility, a major principle for allocation in the context of transplantation, is questioned in patients with acute-on chronic liver failure grade 3 (ACLF-3) who undergo liver transplantation (LT). We aimed to explore long-term outcomes of patients included the three-center retrospective French experience published in 2017., Method: All patients with ACLF-3 (n=73) as well as their transplanted matched controlled with ACLF-2 (n=145), 1 (n=119) and no ACLF (n=292) that have participated in the princeps study published in 2017 were included. We explored 5- and 10-year patient and graft survivals, causes of death and their predictive factors., Results: Median follow-up of patients ACLF-3 patients was 7.5 years. At LT, median MELD was 40. In patients with ACLF-3, 2, 1 and no ACLF, 5-year patients' survivals were respectively 72.6% vs. 69.7% vs. 76.4% vs. 77.0% (p=0.31). Ten-year patients' survival ACLF-3 was 56.8% and was not different other groups (p=0.37) Leading causes of death in ACLF-3 patients were infections (33.3%), and cardiovascular events (23.3%). After exclusion of early death, UCLA futility risk score, age-adjusted Charlson comorbidity index and Chronic Liver Failure Consortium ACLF score were independently associated with 10-year patients' survival. Long-term grafts' survivals were not different across the groups. Clinical frailty scale and WHO performance status improved over time in patients alive after 5 years., Conclusion: 5- and 10-year patients' and grafts' survivals in ACLF-3 patients were not different from their controls. 5-year patients' survival is higher than that of the 50%-70% threshold defining the utility of liver graft. Efforts should focus on candidates' selection based on comorbidities as well as the prevention of infection and cardiovascular events standing as the main cause of death., Impact and Implications: While short-term outcomes following liver transplantation in the most severely ill cirrhotic patients (ACLF-3) are known, long-term data are limited, raising questions about the utility of graft allocation in the context of scarce medical resources. This study provides a favorable long-term update, confirming no differences in 5- and 10-year patient and graft survival following liver transplantation in ACLF-3 patients compared to matched ACLF-2, ACLF-1, and no-ACLF patients. The study highlights the risk of dying from infection and cardiovascular causes in the long-term and identifies scores including comorbidities evaluation, such as the age-adjusted Charlson Comorbidity Index, as independently associated with long-term survival. Therefore, physicians should consider the cumulative burden of comorbidities when deciding to transplant these patients. Additionally, after transplantation, the study encourages mitigating infectious risk with tailored immunosuppressive regimens and managing tightly cardiovascular risk over time., Competing Interests: Declaration of Competing Interest None of the contributing authors has any disclosures related to this work., (Copyright © 2024. Published by Elsevier B.V.)

Background: The SARS-CoV-2 (COVID-19) pandemic required a rapid surge of healthcare capacity to face a growing number of critically ill patients. For this reason, a support reserve of physicians, including surgeons, were required to be reassigned to offer support., Objective: To realize a survey on the educational programs deployed (face-to-face or e-learning focusing on infective area, basic gestures, COVID clinical management and intensive care medicine), and their impact on behavior change (Kirkpatrick 3) of the target population of surgeons, measured on a five modalities Likert scale., Design: Cross-sectional online e-survey (NCT04732858) within surgeons from the Assistance Publique - Hôpitaux de Paris network, metropolitan area of Paris, France., Results: Cross-sectional e-Survey: among 382 surgeons invited, 37 (9.7%) participated. The effectiveness of the educational interventions on behavior changes was rated within the highest region of the Likert scale by 15% ( n  = 3) and 22% ( n  = 6) for 'e-learning' and 'face-to-face' delivery modes, respectively., Conclusions: Despite the low response rate, this survey suggests an overall low impact on behaviour change among responders affiliated to a surgical discipline.

Liver involvement in SCD patients is frequent but often misdiagnosed or underestimated, except in case of advanced liver diseases. Because of so far poorly recognized forms of chronic SCD-related vascular injury that can silently evolved towards end stages or facilitate ACLF, any persisting liver function tests abnormalities should be carefully investigated, following the above proposed algorithm. Work up and management must be considered multidisciplinary in relationship with a Hepatologist. Early SCD hepatopathy should prompt revision of SCD management to prevent further liver injury and decompensation, discussing transfusion exchanges and hydro urea when not yet initiated, and control for any cofactor of liver injury. The role of HSCT in early SCD hepatopathies also deserves evaluation. In advanced SCD hepatopathies, liver transplantation, which has been rarely performed so far, is the only therapeutic option associated with improved survival. It should definitely be discussed- either electively in case of decompensation in SCD cirrhosis or jaundice/recurrent cholangitis in cholestatic diseases, with excellent outcome, - or emergently in case of ALF or ACLF with more mitigate results. To improve knowledge and management of SCD liver diseases, creation of national and international registries, as well as longitudinal observational cohorts are encouraged., Competing Interests: Disclosure of Interest The authors declare that they have no competing interest., (Copyright © 2023. Published by Elsevier Masson SAS.)

Background: Current guidelines suggest the introduction of early nutrition support within the first 48 h of admission to the intensive care unit (ICU) for patients who cannot eat. In that context, we aimed to describe nutrition practices in the ICU and study the association between the introduction of early nutrition support (< 48 h) in the ICU and patient mortality at day 28 (D28) using data from a multicentre prospective cohort., Methods: The 'French-Speaking ICU Nutritional Survey' (FRANS) study was conducted in 26 ICUs in France and Belgium over 3 months in 2015. Adult patients with a predicted ICU length of stay > 3 days were consecutively included and followed for 10 days. Their mortality was assessed at D28. We investigated the association between early nutrition (< 48 h) and mortality at D28 using univariate and multivariate propensity-score-weighted logistic regression analyses., Results: During the study period, 1206 patients were included. Early nutrition support was administered to 718 patients (59.5%), with 504 patients receiving enteral nutrition and 214 parenteral nutrition. Early nutrition was more frequently prescribed in the presence of multiple organ failure and less frequently in overweight and obese patients. Early nutrition was significantly associated with D28 mortality in the univariate analysis (crude odds ratio (OR) 1.69, 95% confidence interval (CI) 1.23-2.34) and propensity-weighted multivariate analysis (adjusted OR (aOR) 1.05, 95% CI 1.00-1.10). In subgroup analyses, this association was stronger in patients ≤ 65 years and with SOFA scores ≤ 8. Compared with no early nutrition, a significant association was found of D28 mortality with early enteral (aOR 1.06, 95% CI 1.01-1.11) but not early parenteral nutrition (aOR 1.04, 95% CI 0.98-1.11)., Conclusions: In this prospective cohort study, early nutrition support in the ICU was significantly associated with increased mortality at D28, particularly in younger patients with less severe disease. Compared to no early nutrition, only early enteral nutrition appeared to be associated with increased mortality. Such findings are in contrast with current guidelines on the provision of early nutrition support in the ICU and may challenge our current practices, particularly concerning patients at low nutrition risk. Trial registration ClinicalTrials.gov Identifier: NCT02599948. Retrospectively registered on November 5th 2015., (© 2023. The Author(s).)

Background: β-lactams are the main antibiotics used against wild-type AmpC-producing Enterobacterales (wtAE). However, they may fail or select AmpC-overproducing mutants. Our aim was to assess factors associated with clinical failure of β-lactams in the treatment of wtAE infection., Methods: From September 2017 to December 2020, we prospectively included all consecutive patients treated by definitive β-lactams therapy for wtAE infection in four university ICUs. Clinical failure was defined as inadequate response to antimicrobial therapy leading to death or to the switch for a broader-spectrum antibiotic., Results: 177 patients were included and 29.4% progressed to clinical failure. E. cloacae was the most prevalent species (42.4%) and ventilator-associated pneumonia (VAP) was the most frequent wtAE infection (69.5%). Cefepime and cefotaxime were used as definitive antibiotic treatment in 42.9% and 27.7% of patients, respectively. Occurrence of AmpC-overproduction was documented in 5.6% of patients and was associated with clinical failure (p = 0.004). In multivariate analysis, VAP (p < 0.001, OR 11.58 [95% CI 3.11-43.02] and K. aerogenes (p = 0.030, OR 3.76 [95% CI 1.13-12.46]) were independently associated with clinical failure. Conversely, cefotaxime as definitive treatment was found inversely associated with the risk of clinical failure (p = 0.022, OR 0.25 [95% CI 0.08-0.82]). After inverse probability weighting, cefotaxime showed a 20% risk reduction of clinical failure (95% CI  5-35%, p = 0.007) whatever the location of infection, the SOFA score on the day of wtAE infection, or the bacterial species., Conclusions: Clinical failure in the treatment of wtAE infections is associated with the infection site and the causal microorganism. Additionally, cefotaxime use is probably protective against clinical failure in wtAE infection., (© 2022. The Author(s).)

Objectives: Direct-acting antiviral (DAA) therapy is currently recommended for most patients chronically infected with the hepatitis C virus (HCV) by the American Association for the Study of Liver Diseases/Infectious Diseases Society of America guidelines. DAAs have significant drug interaction potential, which can lead to treatment failure and adverse drug events. The primary goal of this study is to report the number and nature of interventions made by pharmacists regarding drug interactions in patients using DAA therapy and to estimate the cost avoidance of averting potential DAA treatment failures., Methods: The patients in this cohort were identified through the pharmacy's electronic medical record if they were at least 18 years old while having filled a prescription for a DAA between 6/1/2019 and 06/01/2020. Data for this study were collected retrospectively using a report generated by the pharmacy electronic medical record and through manual chart review. Calculations for cost avoidance associated with prevention of DAA treatment failures are estimations based on the current average wholesale price (AWP) and wholesale acquisition cost (WAC) pricing., Results: A total of 808 patients were identified as filling a prescription for HCV treatment during the measurement period. Average patient age was 49.8 years, and 60.5% of patients were male. A total of 267 patients (33%) were identified as having at least one drug-drug or drug-disease interaction. Of the 304 potential interactions identified, 132 drug interactions (43.9%) could have led to treatment failure and 172 (56%) could have resulted in adverse events. The estimated cost avoidance for interventions made by clinical pharmacists to avert treatment failures (132 regimens) was $387,968 and $323,306 using AWP and WAC pricing, respectively., Conclusion: Pharmacists in the specialty pharmacy setting are essential for the evaluation of potential drug and disease state interactions with HCV therapies. These interventions potentially averted treatment failures and adverse drug events., (Copyright © 2022 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.)

Background: The diagnosis of complex post-traumatic stress disorder (CPTSD) was recently included into the 11th edition of the International Classification of Diseases (ICD-11). Recognizing the need for a brief and specific measure CPTSD symptoms as defined by the ICD-11, Cloitre and her team (2018) developed the original English version of the International Trauma Questionnaire (ITQ). The ITQ is composed of two scales-'post-traumatic stress disorder (PTSD)' and 'disturbances in self-organization' (DSO), respectively subdivided into three subscales. It was found to be psychometrically valid but has yet to be available in French., Objective: The purpose of this study was to provide a French version of the ITQ and to examine its factorial validity, internal consistency, and convergent validity in a French-speaking Canadian sample., Participants: The sample included 335 French-Canadian adults from the community., Methods: The ITQ was translated in French, back translated into English, and deemed equivalent by the original ITQ's author. Participants answered the French version of the ITQ, as well as measures of convergent validity, via phone interview., Results: Confirmatory factorial analyses revealed that the French ITQ presented the same factor structure as the original ITQ. Composite reliability scores revealed good internal consistency for both scales, and all but one subscale. Pearson's correlation and Steiger's Z test revealed good convergent validity., Conclusion: This study supports the factorial validity, internal consistency, and convergent validity of the French version of the ITQ, suggesting that it is a psychometrically sound measure of CPTSD., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Objective: To provide guidelines for the management of the intensive care patient with severe acute pancreatitis., Design: A consensus committee of 22 experts was convened. A formal conflict-of-interest (COI) policy was developed at the beginning of the process and enforced throughout. The entire guideline construction process was conducted independently of any industrial funding (i.e. pharmaceutical, medical devices). The authors were required to follow the rules of the Grading of Recommendations Assessment, Development and Evaluation (GRADE®) system to guide assessment of quality of evidence. The potential drawbacks of making strong recommendations in the presence of low-quality evidence were emphasised., Methods: The most recent SFAR and SNFGE guidelines on the management of the patient with severe pancreatitis were published in 2001. The literature now is sufficient for an update. The committee studied 14 questions within 3 fields. Each question was formulated in a PICO (Patients Intervention Comparison Outcome) format and the relevant evidence profiles were produced. The literature review and recommendations were made according to the GRADE® methodology., Results: The experts' synthesis work and their application of the GRADE® method resulted in 24 recommendations. Among the formalised recommendations, 8 have high levels of evidence (GRADE 1+/-) and 12 have moderate levels of evidence (GRADE 2+/-). For 4 recommendations, the GRADE method could not be applied, resulting in expert opinions. Four questions did not find any response in the literature. After one round of scoring, strong agreement was reached for all the recommendations., Conclusions: There was strong agreement among experts for 24 recommendations to improve practices for the management of intensive care patients with severe acute pancreatitis., (Copyright © 2022. Published by Elsevier Masson SAS.)

The weaker diffusion of echinocandins in the peritoneal fluid (PF) could promote Candida -resistant isolates. The aim of this study was to analyze the pharmacokinetics (PK)/pharmacodynamics (PD) of caspofungin in plasma and PF samples from liver transplant recipients. Liver transplant patients received caspofungin as postoperative prophylaxis. Caspofungin concentrations were quantified in plasma and PF samples on days 1, 3, and 8. Data were analyzed using nonlinear mixed-effect modeling and Monte Carlo simulations. Area under the curve (AUC) values for plasma and PF were simulated under three dosing regimens. Probabilities of target attainment (PTAs) were calculated using area under the unbound plasma concentration-time curve from 0 to 24 h at steady state ( f AUC 0-24 )/MIC ratios, with MICs ranging from 0.008 to 8 mg/L. All of the patients included were monitored weekly for Candida colonization and for Candida infections. Twenty patients were included. The median daily dose of caspofungin was 0.81 mg/kg. Plasma ( n  = 395) and PF ( n  = 50) concentrations at steady state were available. A two-compartment model with first-order absorption and elimination was described. Our two-compartment model with first-order absorption and elimination produced an effective PK/PD relationship in plasma, achieving a PTA of ≥90% with MICs ranging from 0.008 to 0.12 mg/L for Candida albicans and Candida glabrata. In PF, PTAs at D8 were optimal only for a MIC of 0.008 mg/L in patients weighing 60 kg under the three dosing regimens. Among the 16 patients colonized, all MIC values were below the maximal concentration ( C max ) in plasma but not in PF. PF concentrations of caspofungin were low. Simulations showed that the PTAs for Candida spp. in PF were not optimal, which might suggest a potential risk of resistance.