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International audience; Aim: To compare methods of quantifying serum hepcidin (based on MS and ELISA) and their ability to diagnose true iron deficiency anemia in critically ill patients. Materials & methods: Serum hepcidin was measured in 119 critically ill patients included in the HEPCIDANE clinical trial, using either an ultra-sensitive ELISA kit (from DRG) or two different MS methods. Results: The results show a good correlation between the different methods studied. The Bland–Altman analysis and the Kappa test for clinical groups show a good or very good agreement between the different tests. Conclusion: ELISA or MS show a satisfactory commutability to quantify serum hepcidin. This is of great importance for the determination of therapeutic strategies in iron deficiency.

Sağır, Özlem (Balikesir Author), Introduction More than 300 million surgical procedures are performed each year. Acute kidney injury (AKI) is a common complication after major surgery and is associated with adverse short-term and long-term outcomes. However, there is a large variation in the incidence of reported AKI rates. The establishment of an accurate epidemiology of surgery-associated AKI is important for healthcare policy, quality initiatives, clinical trials, as well as for improving guidelines. The objective of the Epidemiology of Surgery-associated Acute Kidney Injury (EPIS-AKI) trial is to prospectively evaluate the epidemiology of AKI after major surgery using the latest Kidney Disease: Improving Global Outcomes (KDIGO) consensus definition of AKI. Methods and analysis EPIS-AKI is an international prospective, observational, multicentre cohort study including 10 000 patients undergoing major surgery who are subsequently admitted to the ICU or a similar high dependency unit. The primary endpoint is the incidence of AKI within 72 hours after surgery according to the KDIGO criteria. Secondary endpoints include use of renal replacement therapy (RRT), mortality during ICU and hospital stay, length of ICU and hospital stay and major adverse kidney events (combined endpoint consisting of persistent renal dysfunction, RRT and mortality) at day 90. Further, we will evaluate preoperative and intraoperative risk factors affecting the incidence of postoperative AKI. In an add-on analysis, we will assess urinary biomarkers for early detection of AKI. Ethics and dissemination EPIS-AKI has been approved by the leading Ethics Committee of the Medical Council North Rhine-Westphalia, of the Westphalian Wilhelms-University Münster and the corresponding Ethics Committee at each participating site. Results will be disseminated widely and published in peer-reviewed journals, presented at conferences and used to design further AKI-related trials. Trial registration number NCT04165369. ©

Background High-density lipoproteins exert pleiotropic effects including antiinflammatory, antiapoptotic, and lipopolysaccharide-neutralizing properties. The authors assessed the effects of reconstituted high-density lipoproteins (CSL-111) intravenous injection in different models of sepsis. Methods Ten-week-old C57BL/6 mice were subjected to sepsis by cecal ligation and puncture or intraperitoneal injection of Escherichia coli or Pseudomonas aeruginosa pneumonia. CSL-111 or saline solution was administrated 2 h after the sepsis. Primary outcome was survival. Secondary outcomes were plasma cell-free DNA and cytokine concentrations, histology, bacterial count, and biodistribution. Results Compared with saline, CSL-111 improved survival in cecal ligation and puncture and intraperitoneal models (13 of 16 [81%] survival rate vs. 6 of 16 [38%] in the cecal ligation and puncture model; P = 0.011; 4 of 10 [40%] vs. 0 of 10 [0%] in the intraperitoneal model; P = 0.011). Cell-free DNA concentration was lower in CSL-111 relative to saline groups (68 [24 to 123] pg/ml vs. 351 [333 to 683] pg/ml; P < 0.001). Mice injected with CSL-111 presented a decreased bacterial count at 24 h after the cecal ligation and puncture model both in plasma (200 [28 to 2,302] vs. 2,500 [953 to 3,636] colony-forming unit/ml; P = 0.021) and in the liver (1,359 [360 to 1,648] vs. 1,808 [1,464 to 2,720] colony-forming unit/ml; P = 0.031). In the pneumonia model, fewer bacteria accumulated in liver and lung of the CSL-111 group. CSL-111–injected mice had also less lung inflammation versus saline mice (CD68+ to total cells ratio: saline, 0.24 [0.22 to 0.27]; CSL-111, 0.07 [0.01 to 0.09]; P < 0.01). In all models, no difference was found for cytokine concentration. 111Indium bacterial labeling underlined a potential hepatic bacterial clearance possibly promoted by high-density lipoprotein uptake. Conclusions CSL-111 infusion improved survival in different experimental mouse models of sepsis. It reduced inflammation in both plasma and organs and decreased bacterial count. These results emphasized the key role for high-density lipoproteins in endothelial and organ protection, but also in lipopolysaccharide/bacteria clearance. This suggests an opportunity to explore the therapeutic potential of high-density lipoproteins in septic conditions. Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New

International audience; Background: Fungus-positive respiratory samples (FPRS) are common in the intensive Care unit (ICU) and are usually considered to correspond to colonization. The management of FPRS during the early postoperative course after lung transplantation (LT) remains unclear. The epidemiology, clinical consequences, and prognosis of FPRS were assessed in LT recipients.Methods: Over a 6-year period, we analyzed the postoperative ICU course of 176 LT recipients with a specific focus on microbiological results of routine respiratory samples and clinical course. The outcomes during the ICU stay at day 28 and at 1 year were compared in patients with or without FPRS. Results are expressed as median and interquartile range.Results: In the pretransplantation period, Candida spp were reported in 17% of patients. No routine post-LT antifungal prophylaxis was initiated. In the post-LT period, at least 1 FPRS was observed in 69% of patients (93% Candida spp, 7% Aspergillus spp). Double LT (odds ratio = 4.15, 95% confidence interval [1.67-11.80], P = .0007) was the only risk factor associated with Candida spp in respiratory samples. Antifungal therapy was administered in 58% of patients with post-LT Candida-positive samples. Candida spp in post-LT respiratory samples were not associated with increased ICU, 28-day, or 1-year mortality rates.Conclusion: A high prevalence of FPRS is reported after LT, mainly with Candida spp. The lack of association between post-LT FPRS and mortality and morbidity suggests avoiding antifungal therapy in the absence of clinical signs of invasive infection.

BACKGROUND Multidrug-resistant (MDR) bacteria are a growing concern worldwide. The aim of this study was to describe the epidemiology and risk factors of MDR bacteria detected in respiratory invasive samples during hospitalization in the intensive care unit (ICU) after lung transplantation (LT). METHODS This study was based on a retrospective analysis of 176 patients hospitalized in the ICU after LT in 2006-2012. Respiratory invasive samples were performed according to a routine protocol. MDR pathogens were defined according to in vitro susceptibility tests. RESULTS A total of 1176 bacteria were cultured. Susceptibility testing was performed on 1046 strains and 404 (39%) MDR were detected in 90 (51%) patients. Pseudomonas aeruginosa, coagulase-negative staphylococci, and Enterobacteriaceae (mainly Enterobacter species) were the most common MDR pathogens. On multivariate analysis, an ICU stay >14 days, presence of a tracheostomy, and previous exposure to broad-spectrum antibiotics were associated with MDR acquisition (odds ratio [OR] 3.7; 95% confidence interval [1.69-8.12]; OR 3.28 [1.05-10.28]; and OR 2.25 [1.17-4.34], respectively). We consistently observed an increasing emergence of resistance to several antibiotics, from week 1 to week 4 of ICU hospitalization: for ticarcillin, piperacillin-tazobactam, ceftazidime, imipenem/cilastatin, amikacin, and ciprofloxacin in P. aeruginosa; and for piperacillin-tazobactam, cefepime, and amikacin in Enterobacteriaceae. CONCLUSION A large proportion of MDR bacteria are detected on respiratory invasive samples in LT patients, and the risk of their emergence is mainly determined by the previous exposure to broad-spectrum antibiotics and the length of ICU stay. Adequate treatment requires broad-spectrum empiric antibiotic therapy.

Iron deficiency (ID) is frequent but difficult to diagnose in critically ill patients. ID may be responsible for prolonged post-ICU hospital stays, since it results in fatigue, muscle weakness and anaemia. Hepcidin, the key iron metabolism hormone, may be a good marker of ID in these patients. The aim of this study is to determine whether using mass spectrometry hepcidin determination to diagnose (and treat) ID after prolonged ICU stays may reduce patients' subsequent hospital stays and costs in comparison with conventional (ferritin) methods.This is a randomised, controlled, single-blinded, multicentre medico-economic study. Hepcidin quantification will be performed in anaemic (WHO criteria) critically ill adults about to be discharged, after a stay ≥5days. In the intervention arm (hepcidin) results will be given to the ICU-physicians, and not in the control arm. ID Treatment will be recommended in intervention arm: IV iron when hepcidin is20μg/L; IV iron+erythropoietin when hepcidin is between 20-41μg/L; in the control arm: IV iron when ferritin300μg/L and Transferrin saturation20%. The primary endpoint will be the number of days spent in hospital 90 days after ICU discharge and the direct hospital costs. Secondary endpoints will be anaemia and iron deficiency on D15, fatigue and the proportion of patients alive and at home on D30 and D90.The results of this study will show whether diagnosing iron deficiency using MS hepcidin determination methods is liable to reduce patients' post-ICU hospital stay and costs, as well as their anaemia and fatigue.

The management of intra-abdominal candidiasis is a challenging issue. Differentiation between colonization and infection is a complex process, which has led to the development of several clinical scores and non-microbiologic tools over recent years. The distinction between colonization and infection is of major importance, as Candida infection is a proven risk factor for mortality in critically ill patients and patients with postoperative peritonitis. The most common pathogens cultured from surgical samples are Candida albicans and, among Candida non-albicans species, C. glabrata, and both of these organisms are also gut commensals in healthy subjects. However, candidemia is rare in these cases. The key issues for the management of these difficult cases are time efficiency and quality of both surgical and medical therapy. Source control is obviously a crucial factor, and the efficacy of source control is reinforced by antifungal therapy. Adequate antifungal therapy requires correct timing, an efficient spectrum, and the right dosage. In critically ill patients and those suspected of harboring azole-resistant strains, a general agreement among the experts and most of the recently published consensus recommends the use of echinocandins, while fluconazole is reserved for low-severity cases and patients with no previous antifungal therapy. Antifungal stewardship is based on de-escalation therapy when possible and limited duration of treatment.

Introduction La transplantation pulmonaire (TP) est la seule option therapeutique des maladies pulmonaires parenchymateuses echappant aux traitements medicamenteux. Les infections pulmonaires, complications frequentes avec un pic d’incidence au cours du mois suivant la TP [1] , sont associees a une morbi-mortalite importante. Afin d’optimiser l’antibiotherapie probabiliste, il est important de bien connaitre les profils de resistance des bacteries responsables de ces infections. Le but de l’etude etait de decrire la frequence d’emergence des bacteries multi-resistantes (BMR) retrouvee sur les prelevements respiratoires au cours du premier mois suivant la TP et leurs facteurs de risque. Materiel et methodes Cette etude retrospective mono-centrique analyse 176 patients (pts) adultes ayant eu une TP sur une periode de 6 ans. Les donnees microbiologiques recoltees proviennent des prelevements respiratoires realises en reanimation au cours des 30 premiers jours (j) suivant la TP. Les BMR sont identifiees selon les recommandations internationales [2] . Les analyses statistiques sont realisees avec le test de Mann-Whitney, le Chi 2 et un modele de regression logistique. Resultats Sur les 1176 bacteries isolees, 404 (34 %) etaient des BMR retrouvees chez 90 pts (51 %) [principalement Pseudomonas aeruginosa (20 % des BMR), Enterobacter spp (19 %), Staphylococcus aureus (11 %) et Stenotrophomonas maltophilia (10 %)]. Les BMR ont emerge en mediane a j9 apres TP. Une correlation etait observee entre le temps depuis la TP et l’emergence des BMR ( r 2 : 0,59 ; p p = 0,0009), la presence d’une tracheotomie (OR : 3,28 [1,05–10,28] ; p = 0,039) et l’utilisation prealable d’un antibiotique a large spectre (OR : 2,25 [1,17–4,34] ; p = 0,016) etaient des facteurs de risque d’emergence de BMR. La sensibilite aux differents antibiotiques decroissait rapidement. La sensibilite globale au cefepime (FEP) diminuait de 81 % a 50 % pour tous les germes identifies entre la 1 e et la 4 e semaine d’hospitalisation en reanimation, la sensibilite a l’imipeneme (IPM) passait de 90 % a 48 %, celle de l’amikacine (AMK) de 85 % a 64 %, celle de la piperacilline–tazobactam (TZP) de 77 % a 50 % ( Fig. 1 ). Discussion Chez nos pts transplantes pulmonaires, une large proportion de BMR a emerge dans un delai median de 9 j. La duree d’hospitalisation en reanimation et la presence d’une antibiotherapie anterieure a large spectre etaient les principaux determinants de cette emergence. Au vu de ces resultats et pour un traitement adapte, une antibiotherapie a large spectre semble necessaire des la phase precoce.

Purpose Postoperative infectious complications are key issues following lung transplantation (LT). Fungal bronchial colonization (FBC) is reported in 40 to 80% of the cases and is usually considered as a complication. The risk factors, morbidity and mortality linked to FBC were assessed in a retrospective monocentric cohort of LT. Methods and Materials From 2006 to 2010, all consecutive LT performed in our institution were included. Demographic and microbiologic data during the first 30 postoperative days after LT were collected. The risk factors of developing FBC and its prognosis were assessed. Results Among 102 LT (emphysema 46%, idiopathic fibrosis 38%), FBC was reported after LT in 52% of the cases in a median delay of 3 [2-5 IQ] days after LT. Only one donor was colonized while 11 % of the recipients were colonized before LT. The main organisms involved in FBC were Candidas (78% of the cases, C albicans (54%), other Candidas species (24%)) while Aspergillus were reported in 9% of the cases. The risk factors associated with FBC are presented in the table 1 . Ischemic bronchitis was reported in 24% of the cases and all of them developed FBC. 75% of FBC were treated by antifungal therapy. Interestingly FBC did not have any impact on length of mechanical ventilation and mortality at day 30. Conclusions FBC is a frequent situation, especially in double LT. The links between ischemic bronchitis and FBC are not clear. FBC in these cases could be a consequence rather than a cause. In patients with identified risk factors (double LT, colonization of conservation liquid), a preemptive antifungal therapy could be discussed. Factors associated with fungal colonization Parameters Odds Ratio 95% IC p Double lung transplantation 3.93 1.49-10.40 0.0037 Hospitalisation >10 days 2.75 1.12-6.77 0.0214 ischemic bronchitis 10.06 2.77-36.66 0.0001 conservation liquid colonization 8.66 0.98-76.11 0.028

Purpose Postoperative infectious complications are key issues following lung transplantation (LT). Early bacterial pneumonia (EBP) worsen prognosis of LT. Assessment of bacterial epidemiology of EBP is necessary to optimize treatment of EBP, thus improving LT outcome. Methods and Materials From 2006 to 2010, all consecutive LT performed in our institution were included. Demographic and microbiologic data during the first 30 postoperative days after LT were collected. Results 102 LT (emphysema 46%, idiopathic fibrosis 38%) were performed during the study period. Among 831 bacteriological cultures of bronchial aspirate, 307 were positive. Evolution of bacterial epidemiology during the first 2 weeks is presented in figure 1 . Donor colonization was associated with recipient infection with Methicilin-sensitive Staphylococcus aureus (MSSA) (OR=5,84; [1,87-18,27], p=0,0033) and Enterobacteria (0R=2,8; [1,15-6,83], p=0,037). Presence of purulent expectoration, contrary to fever, leukocyte count, chest X ray, impairment in lung function and CPIS scor, was associated with positive bacterial cultures (OR=1,99; IC [1,45-2,72] p=0,01). Interestingly, type of bacteria did not have any impact on mortality at day 30. Conclusions There is an evolution of bronchial bacterial epidemiology during the 2 weeks following LT with an increase in Pseudomonas aeruginosa proportion. Only purulent expectoration, but not other parameters currently used to diagnose post operative pneumonia, is associated with positive bacterial culture of bronchial aspiration. These findings highlight the challenging problems raised by the diagnosis of respiratory infection after LT.

Background: Anemia is a significant problem in patients on ICU. Its commonest cause, iron deficiency (ID), is difficult to diagnosed in the context of inflammation. Hepcidin is a new marker of ID. We aimed to assess whether hepcidin levels would accurately guide treatment of ID in critically ill anemic patients after a prolonged ICU stay and affect the post-ICU outcomes. Methods: In a controlled, single-blinded, multicenter study, anemic (WHO definition) critically ill patients with an ICU stay ≥5 days were randomized when discharge was expected to either intervention by hepcidin treatment protocol or control. In the intervention arm patients were treated with intravenous iron (1g of ferric carboxymaltose) when hepcidin was Results: Of 405 randomized patients, 399 were analyzed (201 in intervention and 198 in control arm). 220(55%) had ID at discharge (i.e. an hepcidin vs 33(11;90) days for intervention and control respectively, median difference -1(-3;1) days, p=0.78). D90 mortality was significantly lower in the intervention arm (16(8%) vs 33(16.6%) deaths, absolute risk difference -8.7 (-15.1 to -2.3)%, p=0.008). Conclusion: Treatment of ID diagnosed according to hepcidin levels did not reduce the post-ICU LOS, but may reduce the long-term mortality in critically ill patients about to be discharged after a prolonged stay. Trial Registration: www.clinicaltrial.gov NCT02276690 (October 28, 2014; Retrospectively registered)