Role of gut microbiota and bacterial translocation in acute intestinal injury and mortality in patients admitted in ICU for septic shock

IntroductionSepsis is a life-threatening organ dysfunction with high mortality rate. The gut origin hypothesis of multiple organ dysfunction syndrome relates to loss of gut barrier function and the ensuing bacterial translocation. The aim of this study was to describe the evolution of gut microbiota in a cohort of septic shock patients over seven days and the potential link between gut microbiota and bacterial translocation.MethodsSixty consecutive adult patients hospitalized for septic shock in intensive care units (ICU) were prospectively enrolled. Non-inclusion criteria included patients with recent or scheduled digestive surgery, having taken laxatives, pre- or probiotic in the previous seven days, a progressive digestive neoplasia, digestive lymphoma, chronic inflammatory bowel disease, moribund patient, and pregnant and lactating patients. The primary objective was to evaluate the evolution of bacterial diversity and richness of gut microbiota during seven days in septic shock. Epidemiological, clinical and biological data were gathered over seven days. Gut microbiota was analyzed through a metagenomic approach. 100 healthy controls were selected among healthy blood donors for reference basal 16S rDNA values.ResultsSignificantly lower bacterial diversity and richness was observed in gut microbiota of patients at Day 7 compared with Day 0 (p<0.01). SOFA score at Day 0, Acute Gastrointestinal Injury (AGI) local grade, septic shock origin and bacterial translocation had an impact on alpha diversity. A large increase in Enterococcus genus was observed at Day 7 with a decrease in Enterobacterales, Clostridiales, Bifidobacterium and other butyrate-producing bacteria.DiscussionThis study shows the importance of bacterial translocation during AGI in septic shock patients. This bacterial translocation decreases during hospitalization in ICUs in parallel to the decrease of microbiota diversity. This work highlights the role of gut microbiota and bacterial translocation during septic shock

Etude cas-témoins de morbi-mortalité comparant les lymphomes post-transplantation aux lymphomes survenant dans la population générale

Introduction . Nous avons réalisé une étude cas-témoins (1 :2) de morbi-mortalité pour comparer les lymphomes post-transplantation (LPT) aux lymphomes de la population générale. Méthodes . Vingt-et-un LPT diagnostiqués dans notre centre de transplantation rénale onl été appari és à 42 témoins choisis dans le centre d'hématologie du même hôpital. L'appriement s'est fait sur l'âge, le score pronostique et la présence ou non d'une localisation cérébrale. Seize lymphomes B à grandes cellules et leurs témoins ont ététraités par R-CHOP. Les Iymphomes cérébraux primitifs (5 cas et 10 contrôles) ont reçu une chimiothérapie à base de Methotrexate. Résultats. Les survies globales à 2 ans et à 5 ans étaient respectivement de 57% et44% dans le groupe LPT, contre 71% et 58% dans le groupe témoin (p=0.20). En analyse mullivariée, seul un "Perfomance Status " supérieur à 1 a été identifié comme facteur pronostic indépendant de mortalité (HR 2.68, IC95% [1 .28-5.68], p=0.0 1). Le taux de n!rnission complète après la première ligne de chimiothérapie était similaire dans les deux groupes. La dose-intensité médiane reçue était plus basse dans le groupe PTLD (89% contre 100%, p=0,02). Les décès de complications infectÎeuses et les neutropénies fébriles étaient plus fréquentes dans le groupe PTLD (respectivement 31% contre 0%, p=0.03 el 57% contre 19%, p=0.004). Conclusion. Les LPT semblent de plus mauvais pronostic en comparaison au groupe contrôle bien que cela ne soit pas statistiquement significatif du fait d'un effectif fréduit. Ces mauvais résultats chez les patients greffés seraient liés auxcomplications infectieuses de la chimiothérapie plus qu'à l'agressivité de la maladie hématologiqueIntroduction. There is no consensus on post-transplant Iymphoproliferative disorders (PTLD) best trcatment strategy. Chemotherapy is considered as the therapeutic option with the higher response rate, but no study has compared features and outcomes or PTLD vs Iymphomas observed in the general population (non-PTLD). We perfonned a ca~e- co ntrol (1 :2) sludy 10 compare outcomes in PTLD vs non-PTlD patients after chemotherapy. Methods. Twenty-one PTLD diagnosed since 2000 in a French transplantation center were included and malched to 42 controls treated in the hematology center or the same institution. Cases and contraIs were matched on age, International Prognostic Index (IPI), cerebral localization,histologic type and chemotherapy. Sixteen diffuse large B-celllymphoma (OLBCL) and their controls were treated with cyc!ophosphamide, doxorubicin, oncovin, prednisone and Rituximab (R-CHOP) and 5 primary cerebrallymphomas (PCl) and their conlrols received methouexate-based chemotherapy. Finding. Two-year ovcrall survival (OS) was 57% in PTLD and 71 % in controls and 5-year survival was 44% in PTLD and 58% in control (p=0.20). Response rate 10 first line chemothernpy was similar in balh groups (7 1% in PTLD and 62% in controIs, p=0,58). Median dose intensity was less in PTLD than in controls (89% versus 100%, p=0.02). Febrile neutropen ia and dcath from infectious complications were significantly higher in PTLD vs controIs (respectively 57% vs 19%. p=0,004 and 31% vs 0%, p=0.03). A Performance Status beyond 1 was identified as the only independent risk factor for dealh (HR 2.68, CI 95% [1.28-5.68], p=0.01) in the multivariate analysis. Conclusion. Our study shows that PTLD patients have a poorer prognosis as compared to controls but the difference didn't reach a statistical significance, probably due to the small sample. The poor outcomes obscrved in PTLD are attributed to chemotherapy-induccd infectious complications more than disease's aggressivenessMONTPELLIER-BU Médecine UPM (341722108) / SudocMONTPELLIER-BU Médecine (341722104) / SudocSudocFranceF

Differential effect on mortality of the timing of initiation of renal replacement therapy according to the criteria used to diagnose acute kidney injury: an IDEAL-ICU substudy

Abstract Background This substudy of the randomized IDEAL-ICU trial assessed whether the timing of renal replacement therapy (RRT) initiation has a differential effect on 90-day mortality, according to the criteria used to diagnose acute kidney injury (AKI), in patients with early-stage septic shock. Methods Three groups were considered according to the criterion defining AKI: creatinine elevation only (group 1), reduced urinary output only (group 2), creatinine elevation plus reduced urinary output (group 3). Primary outcome was 90-day all-cause death. Secondary endpoints were RRT-free days, RRT dependence and renal function at discharge. We assessed the interaction between RRT strategy (early vs. delayed) and group, and the association between RRT strategy and mortality in each group by logistic regression. Results Of 488 patients enrolled, 205 (42%) patients were in group 1, 174 (35%) in group 2, and 100 (20%) in group 3. The effect of RRT initiation strategy on 90-day mortality across groups showed significant heterogeneity (adjusted interaction p = 0.021). Mortality was 58% vs. 42% for early vs. late RRT initiation, respectively, in group 1 (p = 0.028); 57% vs. 67%, respectively, in group 2 (p = 0.18); and 58% vs. 55%, respectively, in group 3 (p = 0.79). There was no significant difference in secondary outcomes. Conclusion The timing of RRT initiation has a differential impact on outcome according to AKI diagnostic criteria. In patients with elevated creatinine only, early RRT initiation was associated with significantly increased mortality. In patients with reduced urine output only, late RRT initiation was associated with a nonsignificant, 10% absolute increase in mortality

A Bayesian reanalysis of the Standard versus Accelerated Initiation of Renal-Replacement Therapy in Acute Kidney Injury (STARRT-AKI) trial

Background Timing of initiation of kidney-replacement therapy (KRT) in critically ill patients remains controversial. The Standard versus Accelerated Initiation of Renal-Replacement Therapy in Acute Kidney Injury (STARRT-AKI) trial compared two strategies of KRT initiation (accelerated versus standard) in critically ill patients with acute kidney injury and found neutral results for 90-day all-cause mortality. Probabilistic exploration of the trial endpoints may enable greater understanding of the trial findings. We aimed to perform a reanalysis using a Bayesian framework. Methods We performed a secondary analysis of all 2927 patients randomized in multi-national STARRT-AKI trial, performed at 168 centers in 15 countries. The primary endpoint, 90-day all-cause mortality, was evaluated using hierarchical Bayesian logistic regression. A spectrum of priors includes optimistic, neutral, and pessimistic priors, along with priors informed from earlier clinical trials. Secondary endpoints (KRT-free days and hospital-free days) were assessed using zero–one inflated beta regression. Results The posterior probability of benefit comparing an accelerated versus a standard KRT initiation strategy for the primary endpoint suggested no important difference, regardless of the prior used (absolute difference of 0.13% [95% credible interval [CrI] − 3.30%; 3.40%], − 0.39% [95% CrI − 3.46%; 3.00%], and 0.64% [95% CrI − 2.53%; 3.88%] for neutral, optimistic, and pessimistic priors, respectively). There was a very low probability that the effect size was equal or larger than a consensus-defined minimal clinically important difference. Patients allocated to the accelerated strategy had a lower number of KRT-free days (median absolute difference of − 3.55 days [95% CrI − 6.38; − 0.48]), with a probability that the accelerated strategy was associated with more KRT-free days of 0.008. Hospital-free days were similar between strategies, with the accelerated strategy having a median absolute difference of 0.48 more hospital-free days (95% CrI − 1.87; 2.72) compared with the standard strategy and the probability that the accelerated strategy had more hospital-free days was 0.66. Conclusions In a Bayesian reanalysis of the STARRT-AKI trial, we found very low probability that an accelerated strategy has clinically important benefits compared with the standard strategy. Patients receiving the accelerated strategy probably have fewer days alive and KRT-free. These findings do not support the adoption of an accelerated strategy of KRT initiation

Regional Practice Variation and Outcomes in the Standard Versus Accelerated Initiation of Renal Replacement Therapy in Acute Kidney Injury (STARRT-AKI) Trial: A Post Hoc Secondary Analysis.

ObjectivesAmong patients with severe acute kidney injury (AKI) admitted to the ICU in high-income countries, regional practice variations for fluid balance (FB) management, timing, and choice of renal replacement therapy (RRT) modality may be significant.DesignSecondary post hoc analysis of the STandard vs. Accelerated initiation of Renal Replacement Therapy in Acute Kidney Injury (STARRT-AKI) trial (ClinicalTrials.gov number NCT02568722).SettingOne hundred-fifty-three ICUs in 13 countries.PatientsAltogether 2693 critically ill patients with AKI, of whom 994 were North American, 1143 European, and 556 from Australia and New Zealand (ANZ).InterventionsNone.Measurements and main resultsTotal mean FB to a maximum of 14 days was +7199 mL in North America, +5641 mL in Europe, and +2211 mL in ANZ (p p p p p p p p = 0.007).ConclusionsAmong STARRT-AKI trial centers, significant regional practice variation exists regarding FB, timing of initiation of RRT, and initial use of continuous RRT. After adjustment, such practice variation was associated with lower ICU and hospital stay and 90-day mortality among ANZ patients compared with other regions