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Summary Introduction Prehabilitation is defined as preoperative conditioning of patients in order to improve post-operative outcomes. Some studies showed an increase in functional recovery following colorectal surgery, but its effect in hepato-pancreato-biliary (HPB) surgery is unclear. The aim of this study was to realize a systematic literature review and meta-analysis on the current available evidence on prehabilitation in HPB surgery. Materials and methods A systematic review and a metanalysis were carried out on prehabilitation (physical, nutritional and psychological interventions) in HPB surgery (2009-2019). Assessed outcomes were postoperative complications, length of stay (LOS), 30-day readmission, and mortality. Main results Four studies among the 191 screened were included in this systematic review (3 randomized controlled trials, 1 case-control propensity score study), involving 419 patients (prehabilitation group, n = 139; control group, n = 280). After pooling, no difference was observed on LOS ((−4.37 days [95% CI: −8.86; 0.13]) or postoperative complications (RR 0.83 [95%CI: 0.62; 1.10]), reported by all the included studies. Two trials reported on readmission rate, but given the high heterogeneity, a meta-analysis was not realized. No deaths were reported among the included studies. Conclusion No effect of prehabilitation programs in HPB surgery was observed on LOS or postoperative complications rate. Future trials with standardized outcomes of measure, and adequately powered samples calculations are thus required. PROSPERO registration CRD42020165218.

Resume Introduction La prehabilitation peut etre definie comme un conditionnement preoperatoire des patients afin d’ameliorer les resultats fonctionnels apres chirurgie. Certaines etudes ont montre une meilleure recuperation fonctionnelle apres chirurgie colorectale, mais son impact en chirurgie hepato-bilio-pancreatique (HPB) n’est pas demontre. L’objectif de cette etude est de realiser une revue systematique de la litterature et une meta-analyse des donnees actuellement disponibles sur la prehabilitation en chirurgie HPB. Materiaux et methodes Une revue systematique et une meta-analyse ont ete realisees sur la prehabilitation (interventions physiques, nutritionnelles et psychologiques) en chirurgie HPB (2009–2019). Les criteres de jugement evalues etaient les complications postoperatoires, la duree du sejour, la readmission a 30 jours et la mortalite. Principaux resultats Quatre etudes parmi les 191 examinees ont ete incluses dans cette revue systematique (trois essais controles randomises, une etude cas-temoin sur score de propension) portant sur un total de 419 patients (groupe de prehabilitation, n = 139 ; groupe temoin, n = 280). Apres analyse, aucune difference entre les deux groupes n’a ete observee sur la duree d’hospitalisation (−3,1 jours [IC a 95 % : −6,3 ;0,1]) ni sur le taux de complications postoperatoires (RR 0,83 [IC a 95 % : 0,62 ;1,10]). Deux essais ont evalue le taux de readmission, mais compte tenu d’une heterogeneite elevee, aucune meta-analyse n’a ete realisee. Aucun deces n’a ete rapporte parmi les etudes incluses. Conclusion Sur la base des donnees disponibles il n’a pas ete observe d’impact des programmes de prehabilitation en chirurgie HPB sur la duree d’hospitalisation ou le taux de complications postoperatoires. Des futurs essais avec des criteres de jugement standardises, et avec un echantillon de patients adequat sont necessaires. Prospero Registration CRD42020165218.

Background The Enhanced Recovery Program after surgery is a multimodal, evidence-based protocol of care developed to minimize the response to surgical stress. Data on the influence of ERP on outcomes, particularly according to the complexity of liver surgery, are lacking. Methods A prospective multicenter cohort of patients undergoing liver surgery and exposed to Enhanced Recovery Program from 2016 to 2020 in France was analyzed. High Enhanced Recovery Program compliance was defined as more than 70% of items (15 out of 21). The outcomes were the rate of complications, length of stay, and functional recovery according to Enhanced Recovery Program compliance. Results A total of 297 patients were included in the study, and they had 61.9% overall compliance (median = 13 items, interquartile range 11–15). Complications were observed in 32.2% (n = 95) of cases, and the mean length of hospital stay was 7.28 (±7.15) days overall. A longer duration of liver surgery was associated with an increase in the complication rate, while high compliance was independently associated with a reduced risk of complications in the multivariable analysis. Conclusion High Enhanced Recovery Program compliance was associated with a lower rate of postoperative complications.

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.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.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).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.

BACKGROUND: Critically ill cirrhotic patients are increasingly transplanted, but there is no consensus about futile liver transplantation (LT). Therefore, the decision to delay or deny LT is often extensively debated. These debates arise from different opinions of futility among transplant team members. This study aims to achieve a multinational and multidisciplinary consensus on the definition of futility in LT and to develop well-articulated criteria for not proceeding with LT due to futility. METHODS: Thirty-five international experts from anesthesiology/intensive care, hepatology, and transplant surgery were surveyed using the Delphi method. More than 70% of similar answers to a question were necessary to define agreement. RESULTS: The panel recommended patient and graft survival at 1 year after LT to define futility. Severe frailty and persistent fever or 1 μg/kg per minute and a serum lactate level >9 mmol/L. CONCLUSIONS: Our expert panel provides a consensus on the definition of futile LT and on specific criteria for postponing or denying LT. A framework that may facilitate the decision if a patient is too sick for transplant is presented., SCOPUS: ar.j, info:eu-repo/semantics/published

Resume Le concept d’Acute-on-Chronic Liver Failure (ACLF) decrit un syndrome associant un contexte aigu sur une maladie hepatique chronique, une inflammation et la presence d’au moins une defaillance d’organe. Ce syndrome est associe a une forte mortalite a court terme (mortalite a 28 jours apres l’admission a l’hopital) de l’ordre de 20–25 % chez les patients ayant une defaillance d’organe a plus de 75 % chez les patients presentant trois defaillances ou plus. Les criteres de defaillance d’organe utilises pour definir l’ACLF sont ceux du CLIF SOFA pour chaque organe etudie (hemodynamique, respiratoire, hepatique, coagulation, renale et neurologique). Les patients cirrhotiques avec ACLF sont classes en grade 1 si presence d’une defaillance d’organe, grade 2 (si 2 defaillances), grade 3 (si 3 defaillances ou plus). L’ACLF est present chez 26 % des patients cirrhotiques hospitalises et 8 % le developpent au cours de leur hospitalisation. Il n’existe pas de traitement specifique efficace pour les patients atteints d’ACLF. Le principal objectif du traitement des patients cirrhotiques avec ACLF est de suppleer a la defaillance d’organe, le temps que le traitement de la cause, du facteur declenchant, soit efficace. Dans les formes les plus severes, ce traitement permet de preparer le patient a la transplantation hepatique (notion de « bridge a la transplantation »). La transplantation hepatique est le traitement ultime car seul traitement curatif de la cirrhose. Sa place a emerge ces dernieres annees dans les formes severes chez les patients presentant au moins une defaillance d’organe. Un des objectifs actuels est de prevenir le developpement de l’ACLF chez les patients les plus a risque et/ou de limiter son evolution vers un tableau de defaillance multiviscerale.

The aim of this study was to produce a prognostic model to help predict posttransplant survival in patients transplanted with grade-3 acute-on-chronic liver failure (ACLF-3). Patients with ACLF-3 who underwent liver transplantation (LT) between 2007 and 2017 in 5 transplant centers were included (n = 152). Predictors of 1-year mortality were retrospectively screened and tested on a single center training cohort and subsequently tested on an independent multicenter cohort composed of the 4 other centers. Four independent pretransplant risk factors were associated with 1-year mortality after transplantation in the training cohort: age ≥53 years (P = .044), pre-LT arterial lactate level ≥4 mml/L (P = .013), mechanical ventilation with PaO2 /FiO2 ≤ 200 mm Hg (P = .026), and pre-LT leukocyte count ≤10 G/L (P = .004). A simplified version of the model was derived by assigning 1 point to each risk factor: the transplantation for Aclf-3 model (TAM) score. A cut-off at 2 points distinguished a high-risk group (score >2) from a low-risk group (score ≤2) with 1-year survival of 8.3% vs 83.9% respectively (P

The liver is frequently affected in patients with sickle cell disease (SCD), but few reports have described liver transplantation (LT) in patients with SCD. We present a thorough analysis of the largest single-center series of LT in patients with SCD and the first systematic review. There were 21 patients with a median age of 37.6 years. LT was performed for acute liver failure related to the sickling process (57%) or electively for end-stage liver disease (43%). Prior to LT, 13 patients (62%) were in the intensive care unit and required mechanical ventilation (33%), vasopressor therapy (24%), renal replacement therapy (10%), or molecular adsorbent recirculating system therapy (19%). Post-LT morbidity and mortality were 95% and 33%, respectively. Patient survival at 1 and 5 years were 58.3% and 41.7%, respectively, in the urgent group and 88.9% and 77.8%, respectively, in the elective group. A total of 22 transplant patients with SCD are described in 20 articles in the literature. The 1- and 5-year patient survival rates for the 18 evaluable patients were 75% and 65%, respectively. LT improves survival in patients with SCD and acute liver failure or end-stage liver disease but is associated with high morbidity during the early postoperative course.

The role of robotic surgery for partial mesorectal excision (PME) in patients with high rectal cancer (RC) remains unexplored. This study aimed to compare the operative and postoperative outcomes of robotic (R-PME) versus laparoscopic (L-PME) PME for high RC. This was a single-center propensity score cohort study of consecutive patients diagnosed with RC in the high rectum (>10 to 15 cm from the anal verge) who underwent surgery between September 2012 and May 2019. Of 131 selected patients (50 R-PME and 81 L-PME), 88 were matched using propensity score (44 per group). Operative and postoperative variables were similar between R-PME and L-PME patients, except for operative time (220 min and 190 min, respectively; p

Purpose Corynebacterium spp. (C. spp.) is commonly considered as a contaminant in respiratory specimens. No study has ever focused on its clinical relevance in the lower respiratory tract of patients admitted to the intensive care unit (ICU) and requiring mechanical ventilation. The aims were to describe the characteristics of ICU patients with a C. spp. positive deep respiratory specimen, to investigate the impact of C. spp. on the occurrence of pneumonia, and to evaluate the outcomes of these pneumonia. Methods We retrospectively included all adult patients admitted to ICU in a 1000-bed University Hospital (2007–2017) who had a C. spp. positive lower respiratory tract specimen at a significant quantitative level. We used clinical, radiological, and microbiological criteria to classify the likelihood of such pneumonia. Results Among the 31 patients included, acute respiratory failure and postoperative care after major surgery were the main reasons of admission. SAPS II was 47 [34–60]. C. spp. pneumonia was considered as probable, possible and unlikely in 10, 14, and 7 patients, respectively. Fifty-two and 94% of C. spp. strains were sensitive to amoxicillin, and vancomycin/linezolid, respectively. Seventeen patients had a complete course of antibiotic against C. spp. The overall ICU mortality was 58%. Conclusion Corynebacterium spp seems to be responsible for authentic pneumonia in mechanically ventilated patients. It should be considered as clinically relevant when predominantly present in respiratory specimen from patients suspected with pneumonia in ICU, and empirically treated.

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 (fAUC(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.

International audience; 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.

The French transplant governing system defined “Rescue” (the so-called “Hors Tour”) livers as those livers which were declined for the five top-listed patients. This study compares the outcomes following liver transplantation (LT) in patients who received a donor liver through a rescue allocation (RA) procedure or according to MELD score priority (standard allocation, SA) and evaluates the impact on the graft pool of a proactive policy to accept RA grafts. Data from all consecutive patients who underwent LT with SA or RA grafts from 2011 to 2015 were compared in terms of short- and long-term outcomes. The 249 elective first LTs were performed with 64 (25.7%) RA and 185 (74.3%) SA grafts. RA grafts were obtained from older donors and were associated with a longer cold ischemia time. Recipients of RA livers were older and had lower MELD scores. The rates of delayed graft function, primary nonfunction, retransplantation, complications, and mortality were similar between the RA and SA groups. At 1 and 3 and 5 years, graft and patient survival rates were similar between the groups. These results were maintained after matching on recipient characteristics. Our proactive policy to accept RA grafts increased the liver pool for elective first transplantation by 25%. RA livers can be safely transplanted into selected recipients and significantly expand the liver pool.

Non-tumoral portal vein thrombosis (PVT) is present at liver transplantation in 5% to 26% of cirrhotic patients, and the prevalence of complex PVT as defined here (grade 4 Yerdel, and grade 3,4 Jamieson and Charco) has been reported in 0% to 2.2%. Adequate portal inflow is mandatory to ensure graft and patient survival after liver transplantation. With time, the proposed classifications of non-tumoral chronic PVT have evolved from being anatomy-based, to also incorporating functional parameters. However, none of the currently proposed classifications are directed towards decision-making, regarding the choice of inflow to the graft during transplantation and the outcomes thereof. The present scoping review i) addresses the limits of the currently available classifications in terms of surgical decisiveness, ii) clarifies the concept of physiological or non-physiological portal inflow reconstruction, and subsequently, iii) proposes a new classification of non-tumoral PVT in candidates for liver transplantation; to help tailor the surgical strategy to an individual patient, in order to provide portal inflow to the graft together with control of prehepatic portal hypertension whenever feasible.

International audience; 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.

Liver transplantation for critically ill cirrhotic patients with acute deterioration of liver function associated with extrahepatic organ failures is controversial. While transplantation has been shown to be beneficial on an individual basis, the potentially poorer post-transplant outcome of these patients taken as a group can be held as an argument against allocating livers to them. Although this issue concerns only a minority of liver transplants, it calls into question the very heart of the allocation paradigms in place. Indeed, most allocation algorithms have been centered on prioritizing the sickest patients by using the model for end-stage liver disease score. This has led to allocating increasing numbers of livers to increasingly critically ill patients without setting objective or consensual limits on how sick patients can be when they receive an organ. Today, finding robust criteria to deem certain cirrhotic patients too sick to be transplanted seems urgent in order to ensure the fairness of our organ allocation protocols. This review starts by fleshing out the argument that finding such criteria is essential. It examines five types of difficulties that have hindered the progress of recent literature on this issue and identifies various strategies that could be followed to move forward on this topic, taking into account the recent discussion on acute on chronic liver failure. We move on to review the literature along four axes that could guide clinicians in their decision-making process regarding transplantation of critically ill cirrhotic patients.

The aim of this proof-of-concept study was to evaluate if trained dogs could discriminate between sweat samples from symptomatic COVID-19 positive individuals (SARS-CoV-2 PCR positive) and those from asymptomatic COVID-19 negative individuals. The study was conducted at 2 sites (Paris, France, and Beirut, Lebanon), followed the same training and testing protocols, and involved six detection dogs (three explosive detection dogs, one search and rescue dog, and two colon cancer detection dogs). A total of 177 individuals were recruited for the study (95 symptomatic COVID-19 positive and 82 asymptomatic COVID-19 negative individuals) from five hospitals, and one underarm sweat sample per individual was collected. The dog training sessions lasted between one and three weeks. Once trained, the dog had to mark the COVID-19 positive sample randomly placed behind one of three or four olfactory cones (the other cones contained at least one COVID-19 negative sample and between zero and two mocks). During the testing session, a COVID-19 positive sample could be used up to a maximum of three times for one dog. The dog and its handler were both blinded to the COVID-positive sample location. The success rate per dog (i.e., the number of correct indications divided by the number of trials) ranged from 76% to 100%. The lower bound of the 95% confidence interval of the estimated success rate was most of the time higher than the success rate obtained by chance after removing the number of mocks from calculations. These results provide some evidence that detection dogs may be able to discriminate between sweat samples from symptomatic COVID-19 individuals and those from asymptomatic COVID-19 negative individuals. However, due to the limitations of this proof-of-concept study (including using some COVID-19 samples more than once and potential confounding biases), these results must be confirmed in validation studies.

The aim of this study is to evaluate if the sweat produced by COVID-19 persons (SARS-CoV-2 PCR positive) has a different odour for trained detection dogs than the sweat produced by non COVID-19 persons. The study was conducted on 3 sites, following the same protocol procedures, and involved a total of 18 dogs. A total of 198 armpits sweat samples were obtained from different hospitals. For each involved dog, the acquisition of the specific odour of COVID-19 sweat samples required from one to four hours, with an amount of positive samples sniffing ranging from four to ten. For this proof of concept, we kept 8 dogs of the initial group (explosive detection dogs and colon cancer detection dogs), who performed a total of 368 trials, and will include the other dogs in our future studies as their adaptation to samples scenting takes more time.The percentages of success of the dogs to find the positive sample in a line containing several other negative samples or mocks (2 to 6) were 100p100 for 4 dogs, and respectively 83p100, 84p100, 90p100 and 94p100 for the others, all significantly different from the percentage of success that would be obtained by chance alone.We conclude that there is a very high evidence that the armpits sweat odour of COVID-19+ persons is different, and that dogs can detect a person infected by the SARS-CoV-2 virus.

Drug reaction with eosinophilia and systemic symptoms (DRESS) is a rare severe adverse drug-induced reaction with multiorgan involvement. The outcome and prediction of those patients who develop severe acute liver injury (sALI) or acute liver failure (ALF) remain little known.A multicenter retrospective study of patients admitted with a diagnosis of DRESS-related sALI or ALF. Histological review was performed on liver core biopsies from native livers.Sixteen patients (11 women, 5 men; mean age, 39±17.2 years) were classified as having definite (n=13) or probable (n=3) DRESS. At admission, 3 patients had hepatic encephalopathy; median levels of prothrombin time, INR, and total bilirubin were, respectively, 33% (Q1-Q3, 21-41), 2.74 (1.98-4.50), and 94 μmol/L (Q1-Q3, 39.5-243.5). Nine patients received corticosteroid therapy. Overall, 9 patients improved spontaneously and 7 worsened (liver transplantation [LT] (n=5), deceased (n=2)). Transplantation-free and post-LT survival was 56% and 60%, respectively. After LT, DRESS recurrence was observed in 3 of 5 patients. Systemic corticosteroid therapy was not significantly associated with a clinical improvement. In the multivariate analysis, factor V level less than 40% at day 0 and factor V levels of 40% or greater at admission but decreasing at day 2 were associated with worse outcome. Pathological findings (n=7) revealed atypical lymphoid infiltrates, Kupffer cell hyperplasia with erythrophagocytosis, and an inconstant presence of eosinophils.The spontaneous prognosis of patients with sALI/ALF due to DRESS is poor and was not improved by corticosteroid therapy. Histology is helpful to establish diagnosis. Dynamic variables regarding factor V values are predictive of a poor outcome.

International audience; BACKGROUND: Control of warm ischemia (WI) lesions that occur with donation after circulatory death (DCD) would significantly increase the donor pool for liver transplantation. We aimed to determine whether a novel, oxygenated and hypothermic machine perfusion device (HMP Airdrive system) improves the quality of livers derived from DCDs using a large animal model. METHODS: Cardiac arrest was induced in female large white pigs by intravenous injection of potassium chloride. After 60 minutes of WI, livers were flushed in situ with histidine-tryptophan-ketoglutarate and subsequently preserved either by simple cold storage (WI-SCS group) or HMP (WI-HMP group) using Belzer-MPS solution. Liver grafts procured from heart-beating donors and preserved by SCS served as controls. After 4 hours of preservation, all livers were transplanted. RESULTS: All recipients in WI-SCS group died within 6 hours after transplantation. In contrast, the HMP device fully protected the liver against lethal ischemia/reperfusion injury, allowing 100% survival rate. A postreperfusion syndrome was observed in all animals of the WI-SCS group but none of the control or WI-HMP groups. After reperfusion, HMP-preserved livers functioned better and showed less hepatocellular and endothelial cell injury, in agreement with better-preserved liver histology relative to WI-SCS group. In addition to improved energy metabolism, this protective effect was associated with an attenuation of inflammatory response, oxidative load, endoplasmic reticulum stress, mitochondrial damage, and apoptosis. CONCLUSIONS: This study demonstrates for the first time the efficacy of the HMP Airdrive system to protect liver grafts from lethal ischemic damage before transplantation in a clinically relevant DCD model.

Pectus excavatum can lead to right ventricle compression. Although extremely rare, congestive hepatopathy should be considered when patients with severe pectus excavatum present with cardiovascular involvement.

Background Cirrhosis is not recognised as one of the main risk factors of invasive pulmonary aspergillosis (IPA), although its prevalence is increasing. The aim of our study was to identify factors for IPA in such patients with a positive Aspergillus sp. culture in respiratory samples and to evaluate its impact on outcome. Methods We conducted a monocentric retrospective study between January 2005 and December 2015. All cirrhotic patients hospitalised in our liver ICU with a positive Aspergillus sp. respiratory sample were included. These patients were case-matched with cirrhotic patients without positive Aspergillus respiratory sample. Finally, the patients were classified as having putative aspergillosis or colonisation according to the criteria described previously. Results In total, 986 cirrhotic patients were admitted to ICU during the study period. Among these, sixty patients had a positive Aspergillus sp. respiratory sample. Chronic obstructive pulmonary disease (COPD) comorbidity and organ supports were significantly associated with Aspergillus colonisation. Seventeen patients (28%) were diagnosed as proven or putative IPA and 43 were considered as colonised by Aspergillus sp. The median delay between ICU admission and an IPA diagnosis was 2 [2–24] days. Only COPD was predictive of the presence of IPA (OR 6.44; 95% CI 1.43–28.92; p = 0.0151) in patients with a positive Aspergillus sp. culture. The probability of in-hospital mortality was 71% in the IPA group versus 19% in the colonisation group (p = 0.0001). Conclusion Patients with cirrhosis can be at risk of IPA, especially with COPD. Antifungal agents should be given as soon as possible mainly in cirrhotic patients with COPD.

Background Liver transplant recipients are at high risk of developing invasive aspergillosis and in particular by Aspergillus fumigatus which is the most commonly encountered species in this population. Other non-fumigatus Aspergillus species with reduced susceptibility to antifungal drugs can also be involved. Accurate identification associated to antifungal susceptibility testing is essential for therapy adjustment. We report a case of invasive pulmonary aspergillosis due to Aspergillus pseudodeflectus in a liver transplant recipient. To our knowledge, this is the first reported case of invasive aspergillosis due to this species with a reduced susceptibility to azoles. Case presentation A 64 year-old woman with drug-induced fulminant hepatitis underwent liver transplantation. Prophylactic treatment with caspofungin was introduced due to aspergillosis risk factors consisting in hemodialysis and fulminant hepatitis. Six weeks after transplantation, CT scan showed a right pulmonary opacity associated with an increase of galactomannan (index 5.4). Culture of BAL grew with several colonies of Aspergillus sp. The diagnosis of invasive aspergillosis was probable according to the EORTC criteria. The antifungal susceptibility tests (Etest®) revealed low MICs to echinocandins and amphotericin B) but high MICs to azoles. After these results, voriconazole was switched to liposomal amphotericin B. The patient died one month after diagnosis from a refractory septic shock with multiple organ failure. A molecular identification of isolate, based on partial β-tubulin and calmodulin genes, was performed and identified A. pseudodeflectus. Conclusions Our case raises the question of pathogenicity of this species, which belongs to Aspergillus section Usti and is genetically and morphologically very close to Aspergillus calidoustus that was previously reported in human transplant recipients.

Indocyanine green (ICG) is a water-soluble anionic compound that binds to plasma proteins after intravenous administration. It is selectively taken up at the first pass by hepatocytes and excreted unchanged into the bile. With the development of ICG elimination measurement by spectrophotometry, the ICG retention test has become a safe, rapid, reproducible, inexpensive and noninvasive tool for the assessment of liver function. Clinical evidence suggests that the ICG retention test can enable the establishment of tailored management strategies by providing prognostic information. In particular, this method has been evaluated as a prognostic marker in patients with advanced cirrhosis or awaiting liver transplantation. In addition, it is used as a marker of portal hypertension in cirrhotic patients, as a prognostic factor in intensive care units and for the assessment of liver function in patients undergoing liver surgery. Since recent technology enables ICG-PDR to be measured noninvasively at the bedside, this parameter is an attractive addition to liver function and regional haemodynamic monitoring. However, the current state-of-the-art as concerns this technology remains at a low level of evidence and thorough assessment is required.

Emergency digestive surgery is being increasingly performed in elderly patients. The aim of the present study was to identify the predictors of mortality and morbidity following emergency digestive surgery in patients aged 80 years and older. A single-center retrospective review was performed of consecutive patients aged ≥65 years operated for a digestive surgical emergency between January 2011 and December 2013. Two groups were compared: group A (aged 65–79 years) and group B (aged ≥80 years). The study population included 185 patients: 76 patients in group A and 109 in group B. The mean age was 79.9 years (65–104 years). The overall 90-day mortality rate was 23.2 and 31.9% at 1 year, which was similar between groups. The overall morbidity was 28.6%. No differences were noted between the two groups in overall, minor (Dindo I–II) or major (Dindo III–IV) morbidity rates. Multivariate analysis identified pulmonary disease (odds ratio, OR = 6.43, p = 0.02), bowel ischemia (OR = 11.41, p = 0.01), postoperative ICU stay (OR = 7.37, p

International audience; Donor-derived fungal infections can be associated with severe complications in transplant recipients. Donor-derived candidiasis has been described in kidney transplant recipients where contamination of the preservation fluid (PF) was a commonly proposed source. In liver transplantation, these fungal infections have been less explored. The aim of this study was therefore to determine the incidence and clinical relevance of Candida contamination of preservation fluid in the context of liver transplantation. A 5-year (2008-2012) retrospective multicentre study involving six French liver transplantation centers was performed to determine the incidence of Candida PF contamination. Postoperative clinical features, outcomes in recipients, and risk factors for Candida-related complications of liver transplantation were studied. Candida sp. was isolated from 28 of 2107 preservation fluid samples (1.33%). Candida albicans was the most common yeast (n = 18, 64%). Twenty-two recipients (78.5%) received antifungal therapy (echinocandins in 68%) for 7-37 days. Eight patients developed yeast-related complications (28.6%) including hepatic artery aneurysms (n = 6) and Candida peritonitis (n = 2). The 1-year mortality rate among patients after a yeast-related complication was 62.5%. The incidence of Candida PF contamination was low, but was associated with dramatic postoperative complications and high mortality. Close radiological follow-up may enable early recognition of the arterial complications associated with PF contamination by Candida.

Objectives Appropriate patient selection is important to achieving good outcomes and obviating futile surgery in patients with huge (≥10 cm) hepatocellular carcinoma (HCC). The aim of this study was to identify independent predictors of futile outcomes, defined as death within 3 months of surgery or within 1 year from early recurrence following hepatectomy for huge HCC. Methods The outcomes of 149 patients with huge HCCs who underwent resection during 1995–2012 were analysed. Multivariate logistic regression analysis was performed to identify preoperative independent predictors of futility. Results Independent predictors of 3‐month mortality (18.1%) were: total bilirubin level >34 μmol/l [ P = 0.0443; odds ratio (OR) 16.470]; platelet count of P = 0.0098; OR 5.039), and the presence of portal vein tumour thrombosis ( P = 0.0041; OR 5.138). The last of these was the sole independent predictor of 1‐year recurrence‐related mortality (17.2%). Rates of recurrence‐related mortality at 3 months and 1 year were, respectively, 6.3% and 7.1% in patients with Barcelona Clinic Liver Cancer (BCLC) stage A disease, 12.5% and 14% in patients with BCLC stage B disease, and 37.8% ( P = 0.0002) and 75% ( P = 0.0002) in patients with BCLC stage C disease. Conclusions According to the present data, among patients submitted to hepatectomy for huge HCC, those with a high bilirubin level, low platelet count and portal vein thrombosis are at higher risk for futile surgery. The presence of portal vein tumour thrombosis should be regarded as a relative contraindication to surgery.

Resume Le shunt porto-systemique intrahepatique par voie transjugulaire (TIPS) est un traitement largement utilise, depuis plus de 20 ans, dans les complications de l’hypertension portale telles que l’ascite refractaire ou l’hemorragie digestive par rupture de varices œsophagiennes. L’encephalopathie hepatique apres TIPS est une complication frequente mais rarement grave. Nous rapportons le cas d’un patient ayant presente un etat de mal epileptique revelant un œdeme cerebral avec hypertension intracrânienne au decours de la pose d’un TIPS et faisons une revue de la litterature des cas rapportes. Nous decrivons le developpement de l’encephalopathie hepatique et de l’œdeme cerebral dans les suites d’un TIPS chez les patients atteints d’une maladie chronique du foie.

Invasive fungal infections (IFI) are complications after liver transplantation involving high morbidity and mortality. (1,3)-β-d-glucan (BG) is a biomarker for IFI, but its utility remains uncertain. This study was designed to evaluate the impact of BG following their diagnosis. Between January 2013 and May 2016, 271 liver transplants were performed in our institution. Serum samples were tested for BG (Fungitell®, Associates Cape Code Inc., Falmouth, MA, USA) at least weekly between liver transplantation and the discharge of patients. Nineteen patients (7%) were diagnosed with IFI, including 13 cases of invasive candidiasis (IC), eight cases of invasive pulmonary aspergillosis, and one case of septic arthritis due to Scedosporium apiospernum. Using a single BG sample for the primary analysis of IFI, 95% (21/22) of the subjects had positive BG (>80 pg/mL) at the time of IFI diagnosis. The area under the ROC curves to predict IFI was 0.78 (95% CI: 0.73–0.83). The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of BG for IFI were 75% (95% CI: 65–83), 65% (62–68), 17% (13–21), and 96% (94–97), respectively. Based on their high NPV, the BG test appears to constitute a good biomarker to rule out a diagnosis of IFI.

Background Laparoscopic left hemihepatectomy (LLH) may be an alternative to open (OLH). There are several original variations in the technical aspects of LLH, and no accepted standard. The aim of this study is to assess the safety and effectiveness of the technique developed at Henri Mondor Hospital since 1996. Methods The technique of LLH was conceived for safety and training of two mature generations of lead surgeons. The technique includes full laparoscopy, ventral approach to the common trunk, extrahepatic pedicle dissection, CUSA® parenchymal transection, division of the left hilar plate laterally to the Arantius ligament, and ventral transection of the left hepatic vein. The outcomes of LLH and OLH were compared. Perioperative analysis included intra- and postoperative, and histology variables. Propensity Score Matching was undertaken of background covariates including age, ASA, BMI, fibrosis, steatosis, tumour size, and specimen weight. Results 17 LLH and 51 OLH were performed from 1996 to 2014 with perioperative mortality rates of 0% and 6%, respectively. In the LLH group, two patients underwent conversion to open surgery. Propensity matching selected 10 LLH/OLH pairs. The LLH group had a higher proportion of procedures for benign disease. LLH was associated with longer operating time and less blood loss. Perioperative complications occurred in 30% (LLH) and 10% (OLH) (p = 1). Mortality and ITU stay were similar. Conclusion This technique is recommended as a possible technical reference for standard LLH.

Intensive care information systems (ICIS) implemented in intensive care unit (ICU) were shown to improve patient safety, reduce medical errors and increase the time devolved by medical/nursing staff to patients care. Data on the real impact of ICIS on patient outcome are scarce. This study aimed to evaluate the effects of ICIS on the outcome of critically-ill patients. From January 2004 to August 2006, 1,397 patients admitted to our ICU were enrolled in this observational study. This period was divided in two phases: before the implementation of ICIS (BEFORE) and after implementation of ICIS (AFTER). We compared standard ICU patient's outcomes: mortality, length of stay in ICU, hospital stay, and the re-admission rate depending upon BEFORE and AFTER. Although patients admitted AFTER were more severely ill than those of BEFORE (SAPS II: 32.1±17.5 vs. 30.5±18.5, p=0.014, respectively), their ICU length of stay was significantly shorter (8.4±15.2 vs. 6.8±12.9 days; p=0.048) while the re-admission rate and mortality rate were similar (4.4 vs. 4.2%; p=0.86, and 9.6 vs 11.2% p=0.35, respectively) in patients admitted AFTER. We observed that the implementation of ICIS allowed shortening of ICU length of stay without altering other patient outcomes.

The Simmons-Smith reaction of zinc carbenoids with alkenes is a powerful method to access cyclopropanes containing various substitution patterns. This work exploits the high reactivity of aryldiazomethanes toward zinc halides to generate aryl-substituted carbenoids catalytically. These carbenoids are able to cyclopropanate various alkenes diastereoselectively, including unfunctionalized substrates such as styrenes. The zinc catalyst can be modified to tolerate the use of free allylic alcohols.