39th International Symposium on Intensive Care and Emergency Medicine
2019; BioMed Central; Volume: 23; Issue: S2 Linguagem: Inglês
10.1186/s13054-019-2358-0
ISSN1466-609X
Tópico(s)Sepsis Diagnosis and Treatment
ResumoAccepted abstracts for 39th International Symposium on Intensive Care and Emergency MedicineP001 Prognostic value of a genetic polymorphism of AQP5 in sepsis depends on a source of infectionV Pisarev1, A Chumachenko1, I Tyurin2, R Cherpakov2, A Tutelyan3 1Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology, V.A.Negovsky Institute of General Reanimatology, Moscow, Russia; 2V.M.Buiyanov City Clinical Hospital, Anesthesia-Reanimatology Department, Moscow, Russia; 3Central Institute of Epidemiology, Moscow, RussiaIntroduction: The purpose of the study was to determine whether the preferential localization of the infection and age affect the prognostic value of the genetic marker AQP5 (1364A/C, rs3759129) in outcome prediction in sepsis patients. Studies by Adamzik and colleagues have demonstrated that aquaporin AQP5 polymorphism (1364A/C, rs3759129) associates with increased 30-day survival in sepsis patients presumably due to increased gene expression that enhance the leukocyte migration. To increase the informative value of the prediction and decrease the cost, it might be crucial to determine at a pre-test level the subset of patients who might benefit most from the prognostic genotyping.Methods: Sepsis and septic shock were defined in patients according to SEPSIS-3 (2016) recommendations. Study groups (n=152) included ICU patients with abdominal sepsis (AS, including pancreatitits, peritonitis, cholecystitis, appendicitis; n=98) and sepsis patients with other sources of infections. AQP5 polymorphism was studied by analyzing PCR products in a 2% agarose gel using a AQP5 1364A/C specific tetra primer set. Data were analyzed by Kaplan-Meyer plot and Fisher test, and odds ratios were calculated.Results: Distribution of alleles (A and C) and genotypes (AA, CA and CC) AQP5 1364A/C in patients with sepsis or sepsis subgroups (sepsis with no septic shock and sepsis shock patients) versus control group (healthy volunteers) did not differ. Although there was a trend to preferential survival of sepsis patients with genotype C AQP5 despite the source of infection, only patients with AQP5 CC or CA genotype and abdominal sepsis (Sepsis-3), or a subgroup of the same AQP5 genotype experiencing septic shock, demonstrated increased 30-day survival versus AA homozygotic patients (P<0.002).Conclusions: The informative value of detecting the AQP5 CC or CA genotype for prognosis of 30-day survival versus AA homozygotic patients is increased only in abdominal sepsis patients.P002 Depressed expression of FCER1A gene is associated with increased mortality in infected surgical patientsR Almansa1, C Andrés2, M Martín-Fernández3, S Montero4, C Jambrina5, C Doncel6, J Sánchez-Crespo5, M Heredia-Rodríguez7, J Rico4, C González8, E Sánchez-Barrado5, M Lorenzo-López7, S Martín4, L Muñoz-Bellvis8, M Vaquero5, E Tamayo7, C Aldecoa4, J Bermejo-Martín6 1Hospital Clínico Universitario de Valladolid/IECSCYL, BioSepsis (Group of Biomedical Research in Sepsis), Valladolid, Spain; 2Hospital Clínico Universitario de Valladolid, Clinical Analysis Service, Valladolid, Spain; 3Hospital Clínico Universitario de Valladolid/IECSCYL, BioSepsis (Group for Biomedical Research in Sepsis), Valladolid, Spain; 4Hospital Universitario Rio Hortega, Anesthesiology and Reanimation Service, Valladolid, Spain; 5Hospital Clínico Universitario de Salamanca, Anesthesiology and Reanimation Service, Salamanca, Spain; 6Hospital Clínico Universitario de Valladolid/IECSCYL, BioSepsis (Group for Biomedical Research in Sepsis), Valladolid, Spain; 7Hospital Clínico Universitario de Valladolid, Anesthesiology and Reanimation Service, Valladolid, Spain; 8Hospital Clínico Universitario de Salamanca, Department of General and Gastrointestinal Surgery, Salamanca, SpainIntroduction: Increasing evidence supports a central role for “immunosuppression” in sepsis. It is necessary to develop biomarkers of immune dysfunction that could help to identify patients at risk of poor outcomes [1]. The decreased expression of human leucocyte antigen (HLA)-DRA is proposed as a major feature of immunodepression and its persistent decrease is associated with mortality in sepsis [2]. In a previous study, we evidenced that FCER1A (Fc Fragment Of IgE Receptor Ia) is the gene showing the lowest expression levels of the entire transcriptome in sepsis [3]. Here we studied the association between FCER1A expression and mortality in infected surgical patients.Methods: FCER1A and HLA-DRA expression levels were quantified by droplet digital PCR in blood of 257 infected surgical patients. 26 patients died within 28 days (10.11%). Spearman test was used to evaluate the association between gene expression and the Sequential Organ Failure Assessment (SOFA) score. Areas under Receiver Operating Curves (AUROC) were used to determine the gene expression cut-off values predicting mortality. Kaplan-Meier survival curves were obtained and differences in survival between groups were evaluated using the Log rank test. Cox regression was employed to assess mortality risk at 28 days.Results: Gene expression levels of FCER1A and HLA-DRA correlated inversely with patients’ severity (r: -0.5 p<0.001; r: -0.3, p<0.001 respectively). Both genes showed significant AUROCs to predict survival, but FCER1A showed the best accuracy (Fig. 1). Patients with low levels of FCER1A or HLA-DRA had an increased risk of mortality and died 3 days earlier than non survivors with higher expression levels of these genes (Fig. 2, Table 1-2).Conclusions: Depressed FCER1A gene expression is associated with severity and increased mortality in surgical patients with infection. References 1 Hotchkiss R et al. Lancet Infect Dis 13(3): 260–268, 20132 Cazalis MA et al. Crit Care 10;17(6):R287, 20133 Almansa R et al. J Infect 70(5):445-56, 2015 Table 1 (abstract P002). Predictive capacity of FCER1A gene expression cut-off for 28-day mortality in surgical patients with infection. (COX regression)Full size table Table 2 (abstract P002). Predictive capacity of HLA-DRA gene expression cut-off for 28 day mortality in surgical patients with infection. (COX regression)Full size table Fig. 1 (abstract P002).AUROCs for differential diagnosis of mortality in surgical patients with infectionFull size image Fig. 2 (abstract P002).Kaplan-Meier survival curves. Kaplan-Meier survival curves were established after stratification based on calculated thresholds (optimal operating points of FCER1A (A) and HLA-DRA (B) expression levels)Full size image P003 Genetic markers of nosocomial pneumonia, acute respiratory failure and renal insufficiency in critically ill patientsM Khadzhieva1, O Belopolskaya1, T Smelaya2, A Kuzovlev2, L Salnikova3 1N.I. Vavilov Institute of General Genetics, Russian Academy of Sciences, Moscow, Russia; 2Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology, Moscow, Russia; 3Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology, N.I. Vavilov Institute of General Genetics, Russian Academy of Sciences, Moscow, RussiaIntroduction: Severe pulmonary and renal conditions such as acute respiratory distress syndrome (ARDS), respiratory failure, and deterioration in kidney function often occur in patients with nosocomial pneumonia (NP). The emergence and course of infection is genetically determined, hence host genetic landscape may influence an ability to resist infection.Methods: Variants for genotyping were selected using the PheWAS Catalog which presents genotypic data for 13835 Caucasian patients, 1358 phenotypes and 3144 single nucleotide polymorphisms (SNPs) with P < 0.05 [1]. SNPs with the lowest P-values for phenotypes with both, respiratory and renal manifestations were selected: intergenic variants rs7130588 and rs4980785, rs347344 (EDIL3) and rs2470893 (CYP1A1). CYP1A1 gene was associated with pneumonia and ARDS in our previous investigations, so we included in our analysis three sites of CYP1A1 gene (rs2606345, rs4646903 and rs1048943) studied on a smaller sample. Genotyping was performed on 7 sites for a sample of resuscitation patients with or without NP and other pulmonary complications (n = 354 and n = 216, respectively).Results: Allele rs2606345-G of the CYP1A1 gene was protective against ARDS and an increase in creatinine level (Fig. 1). The rs7130588-G allele was associated with lung complications and with the development of severe respiratory insufficiency (Fig. 2).Conclusions: The SNPs rs2606345 and rs7130588 can influence the aggravation of pulmonary and renal symptoms through genetically mediated response to infection. Reference 1. Denny JC et al. Nat Biotechnol 31: 1102–1110, 2013. Fig. 1 (abstract P003).Protective effect of the rs2606345-G allele (CYP1A1 gene) on the risk of ARDS development (left) and an increase of serum creatinine level on the 14th day after hospitalization (right)Full size image Fig. 2 (abstract P003).Association of the rs7130588-G allele with lung complications (LC) (NP, ARDS, pleurisy, abscess, etc.) (left) and with the development of severe respiratory failure (right)Full size image P004 Mesenchymal stem cells regulate LPS–stimulated macrophages polarization balance by paracrine transforming growth factor betaF LiuSchool of Medicine, Zhongda Hospital, Southeast University, Department of Critical Care Medicine, Nanjing, Jiangsu, ChinaIntroduction: An uncontrolled inflammatory response plays a major role in the sepsis related organ dysfunction. Mesenchymal stem cells(MSCs) can improve survival of sepsis experimental models by modulating the inflammatory response. Macrophages have been considered as important immune effector cells and their polarization imbalance aggravates the disordered inflammation reaction. The project aims to identify the effects of MSCs on macrophages polarization against dysregulated inflammatory response.Methods: RAW264.7 cells were plated in the lower chambers of transwell system in the presence or absence of Lipopolysaccharide (LPS). Then, MSCs were seeded in the upper chambers and incubation for different time. Finally, transforming growth factor beta (TGF-β) receptor (TGF-βR) inhibitor was added in transwell system. The phenotype of RAW264.7 cells were analyzed by flow cytometry, the levels of inflammatory cytokines were detected by Enzyme-linked immunosorbent assay (ELISA).Results: Our data showed that LPS increased the level of interleukin (IL)-6 in RAW264.7 cells (p<0.001) (Fig. 1). In line with IL-6 expression, LPS induced the expression of M1 macrophage (p<0.001). Moreover, LPS stimulated RAW264.7 cells co-culture with MSCs in transwell system, MSCs inhibited the expression of IL-6 and M1 macrophages, while increased M2 macrophages (p<0.001). Compared with LPS group, the concentration of TGF-Β was obviously increased in MSCs treatment groups (p<0.001), furthermore, there were no significantly difference between MSCs directed and indicted groups. More significantly, TGF-βR inhibitor abolished the impact of MSCs on LPS stimulated RAW264.7 cells (p<0.001) (Fig. 2).Conclusions: MSCs polarized M1 macrophages into M2 macrophages and decreased pro-inflammatory cytokine levels by paracrining TGF-β. Fig. 1 (abstract P004).Lipopolysaccharide (LPS) promoted RAW 264.7 M1 polarization. (a): LPS 500 ng/ml stimulated RAW264.7 for 12, 24, 48 and 72 hours, the level of IL-6 significantly increased in a time-dependent manner. (b, c): Flow cytometry showed LPS enhanced the expression of M1 macrophages at all time points. *** P<0.001 compared with control groupFull size image Fig. 2 (abstract P004).TGF-β secreted by MSCs regulated the M1 to M2 in LPS-Stimulated RAW264.7. LPS stimulated RAW264.7 co-culture with MSCs in transwell system for 24, 48 and 72 hours. (a): LPS increased the level of IL-6, whereas MSCs inhibited expression of IL-6. (b, c): MSCs reduced M1 macrophages while increased M2 macrophages in LPS stimulated RAW264.7. (d): The concentration of TGF-β was obviously increased in MSCs directed or in-directed group. (e, f, g): LPS increased IL-6 and M1 macrophages, and MSCs inhibited the IL-6 and M1 macrophages while increased M2 macrophages. TGF-βR inhibitor reversed the effect of MSCs on LPS-stimulated RAW264.7. *P<0.05, **P<0.01, *** P<0.001 compared with control group. # # # P<0.001 compared with LPS stimulated group. &&& P<0.001 compared with MSCs treatment groupFull size image P005 Chronomics in ICU: effect of timing of septic shock onset on circadian rhythm profiles of melatonin and cortisolE Sertaridou1, I Chouvarda2, K Arvanitidis3, E Filidou4, G Kolios3, I Pnevmatikos1 1University Hospital of Alexandroupolis, Intensive Care Unit, Alexandroupolis, Greece; 2Aristotle University of Thessaloniki, Faculty of Medicine, Thessaloniki, Greece; 3Democritus University of Thrace, Faculty of Medicine, Alexandroupolis, Greece; 4Democritus University of Thrace, Faculty of Mrdicine, Alexandroupolis, GreeceIntroduction: Circadian rhythmicity of melatonin and cortisol has been found to be affected by sepsis in both experimental and clinical studies.Methods: In this study, we evaluated the potential effect of septic shock on circadian rhythms of urinary excreted aMT6s, a melatonin’s metabolite and cortisol in 26 patients, divided into two groups: Group A (N=15) included subjects with septic shock upon admission to the ICU and Group B (N= 11) included patients who developed septic shock during ICU stay. Urine samples were collected every 4 h over a 24-h period, whereas data were available during entry and before discharge from the ICU in Group A and during entry, septic shock and before exit from the ICU in Group B. Circadian analysis was performed leading to the estimation of mesor (mean value), amplitude of the oscillation and acrophase (phase shift of maximum values in hours).Results: Circadian markers of aMT6s and cortisol exhibited inverse changes, both within and between groups, since amplitude of aMT6s was reduced in entry in relation to exit (437.2±309.2 vs 674.1±657.6 ng/4h, p<0.05), whereas amplitude of cortisol was increased upon admission compared to exit (13.3±31 ng/4h vs 8.7±21.2 ng/4h p<0.05), in Group A. Furthermore, in Group B, mesor of aMT6s was increased during septic shock (2492.2± 1709.1 ng/4h) compared to both entry (895.4±715.5 ng/4h) and exit (1308.6± 1214.4 ng/4h, p<0.05 for all comparisons). However, cortisol’s mean values were reduced during septic shock (10±5.3 ng/4h) compared to both entry (30±57.9 ng/4h) and exit (14.4±20.7 ng/4h, p<0.05 for all comparisons) and correlated with higher APACHE II score and longer ICU and hospital stay (p 3 hours, and had an echocardiogram within 12 months were included. Patients were divided into two groups: reduced ejection fraction (EF) of < 40% and preserved EF defined as EF ≥40%. Information about patient outcomes and sepsis management were collected. The primary outcome was the need for mechanical ventilation (MV). Categorical and continuous data were analyzed using the Chi-Squared and Mann-Whitney U tests, respectively. The IRB has approved this project.Results: A total of 37 patients with EF < 40% and 42 patients with EF ≥40% were included. No significant differences in fluid management, vasoactive agent maximum rate or duration, or steroid use were observed. Net fluid balance between low and preserved EF was positive 4.6 liters vs. 5.1 liters (p = 0.814), respectively. The number of patients that needed MV was higher in the low EF cohort (86% vs. 57%, p = 0.004), and this cohort had fewer MV-free days (20, IQR 0-25 vs. 24 (IQR 0 -28), p=0.064.Conclusions: No significant differences were observed with regard to sepsis management, reflecting current guidelines. The significantly increased need for MV is a provocative result. A potential mechanism is the inability of a patient with reduced LV dysfunction to maintain appropriate cardiac and respiratory function in the face of fluid overload. Prospective analysis of the role of fluid balance in septic patients with LV dysfunction is warranted.P008 Biomarkers of myocardial injury and cytokine plasma levels in septic patientsM Assuncao1, FR Machado2, MK Brunialti3, O Rigato4, R Salomao3 1Hospital Israelita Albert Einstein, Department of Critical Care, Sao Paulo, Brazil; 2Federal University of Sao Paulo, Department of Anesthesiology, Pain and Intensive Care, Sao Paulo, Brazil; 3Federal University of Sao Paulo, Division of Infections Diseases, Sao Paulo, Brazil; 4Hospital Sirio Libanes, Department of Critical Care, Sao Paulo, BrazilIntroduction: The relationship between myocardial injury and systemic inflammation in sepsis response is not well understood [1]. It´s proposed to evaluate the association between myocardial injury biomarkers, high-sensitive troponin T (hs-cTnT) and N-terminal pro-brain natriuretic peptide (NT-ProBNP), with inflammatory mediators (IL-6, IL-1Β , IL-8, IL-10, IL-12 / IL-23p40, IL17A, IL- 21 and TNF-α ) and biomarkers, C protein reactive (CPR) and procalcitonin (PCT), in septic patientsMethods: This was a prospective cohort study performed in three intensive care units, from September 2007 to September 2010 enrolling patients with sepsis (infection associated with organ dysfunction), and septic shock (hypotension refractory by fluids infusion requiring vasopressor). Blood samples were collected up to 48h after the development of first organ dysfunction (D0) and on the 7th day after inclusion in the study (D7)Results: Ninety-five patients were enrolled, with median age 64 years (interquatile?48–78), APACHE II: median 19 (14-22), SOFA: median 8 (5-10); 24.2% were admitted in ICU with sepsis and 75.8% with septic shock. Hospital mortality was 34.7%. In D0, NT-ProBNP correlated with IL-8 (r = 0.495, p <0.001) and IL-10 (r = 0.471, p <0.001). In D7, hs-cTnT and NT-ProBNP correlated with PCT (r = 0.446, p < 0.001 and r = 0.495, p < 0.001; respectively). NT-ProBNP D0 was higher in non-survivors than in survivors on mortality in seventh day (p = 0.029) and in-hospital mortality (p = 0.030). hs-cTnT D7 (p = 0.030) and NT-ProBNP D7 (p <0.001) were significantly higher in non-survivors on in-hospital mortality. NT-ProBNP D7 (OR 9.28; IC95% 2.05-41.94, p=0,004) and hs-cTnT D7 (OR 10,93; IC95% 2.139 – 55.795, p=0,04) were independently associated with in-hospital mortalityConclusions: NT-ProBNP plasma levels at D0 correlated with IL-8 and IL-10, and both NT-ProBNP and hs-cTnT at D7 correlated with PCT. In addition, NT-ProBNP has been shown to be an important predictor of mortality Reference 1. Landesberg G et al. Chest. 2015;148:93-102.P009 Repeated measures of heparin-binding protein correlate with mean arterial pressure and systemic vascular resistance index in septic shock: a pilot study on biomarker kinetics from a Swedish intensive care unitJ Tverring1, N Nielsen2, F Kahn3, A Linder3, P Åkesson3 1Division of Infection Medicine, BMC, B14, Faculty of Medicine, Department of Clinical Sciences, Lund, Sweden; 2Division of Anesthesiology and Intensive Care, Department of Clinical Sciences, Lund, Sweden; 3Division of Infection Medicine, BMC, B14, Lund, SwedenIntroduction: Heparin-binding protein (HBP) acts proinflammatory on immune cells and induces vascular leakage through cytoskeletal rearrangement and cell contraction in the endothelium and is a promising novel prognostic biomarker in sepsis and septic shock. However, studies on repeated measures of HBP are lacking. Our objective was to describe the kinetics of plasma HBP during septic shock and correlate it to hemodynamic parameters.Methods: We included patients with septic shock (sepsis-3) on admission to Helsingborg hospital’s intensive care unit (ICU) during September 2016 to February 2018. Patients were sampled from ICU admission and every 4 hours for 72 hours or until death or ICU discharge. The plasma samples were analyzed for HBP and converted using the natural log (lnHBP) for normality. lnHBP was then evaluated against mean arterial pressure (MAP) as primary analysis and against systemic vascular resistance index (SVRI) as a secondary analysis, using mixed-effects linear regression models, treating patient id as a random intercept and adjusting for hemodynamic parameters.Results: A total of 22 patients were included with median age 67 years, 9 females (41%), 7 surgical admissions (32%), median SOFA-score 12 points on day one and 6 deaths from all causes within 90 days (27%). Plasma HBP ranged from 0 to 932 ng/ml with a median of 47 ng/ml (lnHBP range 1.6 to 6.8, median: 3.9). An increase lnHBP was significantly associated with a decrease in MAP (Coef. -2.58 mmHg, 95% CI: -0.62 to -4.55, p=0.010, n=22), when adjusting for heart rate (HR), noradrenaline (NA), vasopressin (VP), dobutamine (DBT) and levosimendan (LS). In a secondary subgroup analysis, an increase in lnHBP was also significantly associated with a decrease in SVRI (Coef. -94.2 dyne*s*cm-5*m-2, 95% CI: -1.3 to -187.1, p=0.047, n=13), when adjusting for MAP, HR, NA, VP, DBT, LS and cardiac index.Conclusions: Repeated measures of plasma HBP during septic shock were correlated with important hemodynamic parameters in this small pilot study.P010 Mid-regional pro-adrenomedullin (MR-proADM) as early mortality predictor in septic shockV Lovati, F Marsigli, E PierucciAzienda Ospedaliero Universitaria Policlinico Sant´Orsola Malpighi, Dipartimento di Scienze Mediche e Chirurgiche, Bologna, ItalyIntroduction: Mid-regional pro-Adrenomedullin (MR-proADM) comes from the synthesis of the hormone adrenomedullin (ADM), which is overexpressed during inflammation and progression from sepsis to septic shock. Thus, MR-proADM can be a useful biomarker for the clinical management of septic patients [1]. The aim of our study was to understand the ability of MR-proADM to predict 30-day (30-d) mortality and to find a correlation between MR-proADM and Sequential Organ Failure Assessment (SOFA) score in the first 24 hours from Intensive Care Unit (ICU) admission.Methods: We evaluated 28 consecutive septic shock patients according to 2016 Sepsis III definitions. Clinical data from the medical records included demographics, comorbidities, laboratories, microbiology and biomarker levels. Whole blood samples for biomarker profiling were collected at 24, 72 and 120 hours from ICU admission. MR-proADM measurement was detected in EDTA plasma using a sandwich immunoassay by TRACE® (Time Resolved Amplified Cryptate Emission) technology (Kryptor Thermo Fischer Scientific BRAHMS).Results: Overall 30-d mortality rate was 50.0%. MR-proADM [odds ratio (OR) = 1.195], SOFA score (OR = 2.174) and Lactate (Lac) levels (OR = 1.956) in the first 24 hours were associated with 30-d mortality in univariate logistic analysis (P value < 0.05, Table 1). 30-d mortality rate was not associated with procalcitonin (PCT) levels (OR = 1.002). Further linear regression analysis showed significant correlation between MR-proADM and SOFA score at 24 hours from ICU admission (P value<0.001, Fig. 1, Table 2).Conclusions: MR-proADM demonstrated superior accuracy to predict 30-d mortality compared to PCT levels and is directly linked to SOFA score at 24 hours from admission. MR-proADM may aid early identification of poor prognosis septic patients who could benefit a more intensive management. Reference 1. Andaluz-Ojeda D. et al. Ann Intensive Care 7, 15 (2017) Table 1 (abstract P010). Univariate logistic analysis between 30-day mortality, MR-proADM, SOFA score, lactate levels, PCT levelsFull size table Table 2 (abstract P010). Linear regression analysis between MR-proADM and SOFA score related to Fig. 1Full size table Fig. 1 (abstract P010).Linear regression analysis between MR-proADM and SOFA score at 24h from ICU admission: SOFA score = Coeff. x MR-proADM + Const. Coeff. = 0.3211 L/nmol Const. = 8.5158Full size image P011 Pre-sepsin as diagnostic and prognostic marker in sepsis: prospective evaluation by test and confirmation cohortsN Melachroinopoulos1, S Pouriki2, A Prekates3, K Toutouzas4, C Mathas5, E Giamarellos-Bourboulis6 1National and Kapodistrian University of Athens, Athens, Greece; 2Hippokrateion General Hospital, Athens, Greece; 3Tzaneion General Hospital, Intensive Care Unit, Piraeus, Greece; 4National and Kapodistrian University of Athens, 1st Department of Propedeutic Surgery, Athens, Greece; 5Konstantopouleion General Hospital, Intensive Care Unit, Athens, Greece; 6National and Kapodistrian University of Athens, 4th Department of Internal Medicine, Athens, GreeceIntroduction: Biomarkers have not yet been studied in prospective studies using Sepsis-3. The diagnostic and prognostic validity of pre-sepsin (soluble CD14) was studied in both one test and one confirmation cohort.Methods: The test cohort was the prospective clinical study INTELLIGENCE-1 (ClinicalTrials.gov NCT03306186) enrolling patients with documented infections and at least one qSOFA sign. The confirmation cohort was the prospective clinical study INTELLIGENCE-2 (ClinicalTrials.gov NCT03306186) with patients admitted in the emergencies with at least one qSOFA sign. Blood samples were collected within the first 24 hours of the presence of the qSOFA criteria and pre-sepsin was measured in plasma using the PATHFAST assay. Patients were classified as sepsis and non-sepsis using Sepsis-3 definitions; 28-day mortality was recorded.Results: In the test cohort, 62 patients were classified as non-sepsis and 111 as sepsis. Using ROC curve analysis, it was found that the best trade-off between sensitivity and specificity was provided at 350 pg/ml. The odds ratio for sepsis with presepsin above 350 pg/ml was 4.04 (p<0.0001) providing diagnostic sensitivity 80.2%. In logistic regression analysis, it was found that Charlson’s comorbidity index more than 2, history of type 2 diabetes mellitus and of chronic obstructive pulmonary disease and presepsin more than 350 pg/ml were the only variables independently associated with sepsis. Presepsin above 350 pg/ml was associated with sensitivity 91.5% for 28-day mortality. The odds ratio for mortality with presepsin above 350 pg/ml was 6.84 (p: 0.001). In the confirmation cohort, 59 patients were enrolled. The sensitivity of presepsin above 350 pg/ml for the diagnosis of sepsis was 85.7% and for the prediction of 28-day mortality 100%.Conclusions: Using a test and confirmation cohort approach, presepsin above 350 pg/ml was proved a valuable indicator for the diagnosis of sepsis and outcome prognosis among the most severe patients with one qSOFA sign.P012 Toll-like receptors as biomarkers of sepsis in the emergency departmentC Graham, LY Leung, R Lo, YK Leung, K HungThe Chinese University of Hong Kong
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