Circulating adrenomedullin estimates survival and reversibility of organ failure in sepsis: the prospective observational multinational Adrenomedullin and Outcome in Sepsis and Septic Shock-1 (AdrenOSS-1) study

Background: Adrenomedullin (ADM) regulates vascular tone and endothelial permeability during sepsis. Levels of circulating biologically active ADM (bio-ADM) show an inverse relationship with blood pressure and a direct relationship with vasopressor requirement. In the present prospective observational multinational Adrenomedullin and Outcome in Sepsis and Septic Shock 1 (, AdrenOSS-1) study, we assessed relationships between circulating bio-ADM during the initial intensive care unit (ICU) stay and short-term outcome in order to eventually design a biomarker-guided randomized controlled trial. Methods: AdrenOSS-1 was a prospective observational multinational study. The primary outcome was 28-day mortality. Secondary outcomes included organ failure as defined by Sequential Organ Failure Assessment (SOFA) score, organ support with focus on vasopressor/inotropic use, and need for renal replacement therapy. AdrenOSS-1 included 583 patients admitted to the ICU with sepsis or septic shock. Results: Circulating bio-ADM levels were measured upon admission and at day 2. Median bio-ADM concentration upon admission was 80.5 pg/ml [IQR 41.5-148.1 pg/ml]. Initial SOFA score was 7 [IQR 5-10], and 28-day mortality was 22%. We found marked associations between bio-ADM upon admission and 28-day mortality (unadjusted standardized HR 2.3 [CI 1.9-2.9]; adjusted HR 1.6 [CI 1.1-2.5]) and between bio-ADM levels and SOFA score (p < 0.0001). Need of vasopressor/inotrope, renal replacement therapy, and positive fluid balance were more prevalent in patients with a bio-ADM > 70 pg/ml upon admission than in those with bio-ADM ≤ 70 pg/ml. In patients with bio-ADM > 70 pg/ml upon admission, decrease in bio-ADM below 70 pg/ml at day 2 was associated with recovery of organ function at day 7 and better 28-day outcome (9.5% mortality). By contrast, persistently elevated bio-ADM at day 2 was associated with prolonged organ dysfunction and high 28-day mortality (38.1% mortality, HR 4.9, 95% CI 2.5-9.8). Conclusions: AdrenOSS-1 shows that early levels and rapid changes in bio-ADM estimate short-term outcome in sepsis and septic shock. These data are the backbone of the design of the biomarker-guided AdrenOSS-2 trial. Trial registration: ClinicalTrials.gov, NCT02393781. Registered on March 19, 2015

Different epidemiology of bloodstream infections in COVID-19 compared to non-COVID-19 critically ill patients: A descriptive analysis of the Eurobact II study

Background: The study aimed to describe the epidemiology and outcomes of hospital-acquired bloodstream infections (HABSIs) between COVID-19 and non-COVID-19 critically ill patients. Methods: We used data from the Eurobact II study, a prospective observational multicontinental cohort study on HABSI treated in ICU. For the current analysis, we selected centers that included both COVID-19 and non-COVID-19 critically ill patients. We performed descriptive statistics between COVID-19 and non-COVID-19 in terms of patients’ characteristics, source of infection and microorganism distribution. We studied the association between COVID-19 status and mortality using multivariable fragility Cox models. Results: A total of 53 centers from 19 countries over the 5 continents were eligible. Overall, 829 patients (median age 65 years [IQR 55; 74]; male, n = 538 [64.9%]) were treated for a HABSI. Included patients comprised 252 (30.4%) COVID-19 and 577 (69.6%) non-COVID-19 patients. The time interval between hospital admission and HABSI was similar between both groups. Respiratory sources (40.1 vs. 26.0%, p < 0.0001) and primary HABSI (25.4% vs. 17.2%, p = 0.006) were more frequent in COVID-19 patients. COVID-19 patients had more often enterococcal (20.5% vs. 9%) and Acinetobacter spp. (18.8% vs. 13.6%) HABSIs. Bacteremic COVID-19 patients had an increased mortality hazard ratio (HR) versus non-COVID-19 patients (HR 1.91, 95% CI 1.49–2.45). Conclusions: We showed that the epidemiology of HABSI differed between COVID-19 and non-COVID-19 patients. Enterococcal HABSI predominated in COVID-19 patients. COVID-19 patients with HABSI had elevated risk of mortality. Trial registration ClinicalTrials.org number NCT03937245. Registered 3 May 2019

Simple scoring system to predict in-hospital mortality after surgery for infective endocarditis

BACKGROUND: Aspecific scoring systems are used to predict the risk of death postsurgery in patients with infective endocarditis (IE). The purpose of the present study was both to analyze the risk factors for in-hospital death, which complicates surgery for IE, and to create a mortality risk score based on the results of this analysis. METHODS AND RESULTS: Outcomes of 361 consecutive patients (mean age, 59.1\ub115.4 years) who had undergone surgery for IE in 8 European centers of cardiac surgery were recorded prospectively, and a risk factor analysis (multivariable logistic regression) for in-hospital death was performed. The discriminatory power of a new predictive scoring system was assessed with the receiver operating characteristic curve analysis. Score validation procedures were carried out. Fifty-six (15.5%) patients died postsurgery. BMI >27 kg/m2 (odds ratio [OR], 1.79; P=0.049), estimated glomerular filtration rate 55 mm Hg (OR, 1.78; P=0.032), and critical state (OR, 2.37; P=0.017) were independent predictors of in-hospital death. A scoring system was devised to predict in-hospital death postsurgery for IE (area under the receiver operating characteristic curve, 0.780; 95% CI, 0.734-0.822). The score performed better than 5 of 6 scoring systems for in-hospital death after cardiac surgery that were considered. CONCLUSIONS: A simple scoring system based on risk factors for in-hospital death was specifically created to predict mortality risk postsurgery in patients with IE

Impact of MICA and NKG2D polymorphisms in HLA-fully matched related and unrelated hematopoietic stem cell transplantation

International audienc

SLEEP OBSTRUCTIVE APNEA SYNDROME (SOAS) IS NOT ASSOCIATED WITH MARKED ERYTHROCYTOSIS. A STUDY ON 337 PATIENTS

21st Congress of the European-Hematology-Association, Copenhagen, DENMARK, JUN 09-12, 2016International audienc

SLEEP OBSTRUCTIVE APNEA SYNDROME (SOAS) IS NOT ASSOCIATED WITH MARKED ERYTHROCYTOSIS. A STUDY ON 337 PATIENTS

21st Congress of the European-Hematology-Association, Copenhagen, DENMARK, JUN 09-12, 2016International audienc

Immunomodulation with azacytidine and donor lymphocyte infusion following sequential conditioning allogenic stem cell transplantation improves outcome of unfavorable AML

61st Annual Meeting and Exposition of the American-Society-of-Hematology (ASH), Orlando, FL, DEC 07-10, 2019International audienceBackground:Patients with acute myeloid leukemia in relapse or refractory to induction therapy have dismal prognosis. Response rates to common salvage regimens are low and allogenic hematopoietic stem cell transplantation is the only curative option. Several studies have demonstrated that salvage chemotherapy with sequential conditioning could reduce leukemia relapse risk with an acceptable toxicity profile for unfavorable acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). [1] Therefore, we decided to assess this procedure in our center at Amiens University Hospital.MethodsWe conducted a monocentric retrospective study, including 53 patients aged over 18 years undergoing a hematopoietic stem cell transplant (HSCT) with sequential conditioning between January 2012 and December 2018, for relapse/refractory AML or high risk MDS. 44 (83%) patients received sequential conditioning containing clofarabine (SET-RIC) or Amsacrine (FLAMSA) and 9 (17%) thiotepa based (TEC-RIC) with post-transplant cyclophosphamide for mismatched donors. Patients who were GVHD free after immunosuppressors withdrawal received immunomodulation as relapse prevention with azacytidine 37.5mg/m²/day 5 days every 4 weeks for 12 cycles with 3 donor lymphocyte infusions (DLI) alterned between azacytidine cycles.ResultsThe median age was 52 years (range 18-70). Before conditioning, 48 patients had unfavorable AML with ELN intermediate score refractory to at least one course of induction therapy or in relapse, or unfavorable ELN score; 5 patients had high risk MDS with complex karyotype. 32 patients (60,5%) had active disease and 21 (39,5%) were in complete remission (CR) including 12 with positive MRD. 13 (24,5%) patients had HLA-identical sibling donors, 27 (51%) match unrelated donors (MUD), 4 (7,5%) mismatch unrelated donors (MMD) and 9 (17%) haploidentical donors. Majority of patients (90,5%) received peripheral blood stem cell (PBSC) PBSC with median CD34+ count of 7,94.106/kg (1,84-8,44). Acute GvHD prophylaxis with Ciclosporin A, in combination with Mycophenolate mofetil for MUD/MMR/Haplo, was withdrawal with a median time of 90 days.With a median follow-up of 40 months, overall survival (OS) at 1 and 2 years was 68% and 52%. Median OS was 18,7 months (0-72,4 months) and median disease free survival (DFS) was 14,9 months (0-72,4 months). 17 patients (32%) experienced relapse after HSCT with a median time from HSCT to relapse of 6 months (1-35 months). 22 (41,5%) of patients presented with grade I-II acute graft versus host disease (GVHD) and 6 (11,3%) with grade III IV aGVHD . GVHD free relapse free survival (GRFS) at 1 and 2 years was 53% and 34,2%. One-year cumulative incidence of disease related death and non-relapse mortality was 12,6% and 17% respectively. 19 patients received immunomodulation with 5 Azacitidine and DLI if no GVHD occurred within day 120. OS was 79 % in the 19 patients receiving DLI. In univariate analysis immunomodulation post HSCT (Figure 1) was significantly associated with overall survival and leukemia free survival (p=0,0164 and p=0,0359 respectively) but not the disease status before HSCT (p=0,7). Immunomodulation administration with azacytidine and DLI was not significantly associated with cGVHD occurrence (p=0.31). Benefit of immunomodulation OS persisted in multivariate analysis (p=0.0284).Conclusion:Sequential conditioning regimen on refractory AML with secondary immunomodulation with azacytidine and DLI shows very good results with an acceptable toxicity profile in unfavorable AML. We achieve very good OS and DFS whatever disease status before HSCT. GRFS is also encouraging comparing to previously report datas [1]

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CNRS-CDST / INIST-CNRS - Institut de l'Information Scientifique et TechniqueSIGLEFRFranc

Sequential conditioning in unfavorable AML: a single center experience

44th Annual Meeting of the European-Society-for-Blood-and-Marrow-Transplantation (EBMT), Lisbon, PORTUGAL, MAR 18-21, 2018International audienc