Assessment of plasma 12(S)-Hydroxyeicosatetraenoic acid as a biomarker to predict mortality in adults with severe trauma.
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ABSTRACT:
SUBMITTER: Yang L
PROVIDER: S-EPMC7459147 | biostudies-literature | 2020
REPOSITORIES: biostudies-literature
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Assessment of plasma 12(S)-Hydroxyeicosatetraenoic acid as a biomarker to predict mortality in adults with severe trauma.
Yang Liping L Cheng Qian Q Huang Qi Q Liang Huaping H Luo Yan Y
Burns & trauma 20200831
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Project description:Importance:Optimal transfusion management is crucial when treating patients with trauma. However, the association of an early, high transfusion ratio of fresh frozen plasma (FFP) to packed red blood cells (PRBC) with survival remains uncertain. Objective:To study the association of an early, high FFP-to-PRBC ratio with all-cause 30-day mortality in patients with severe bleeding after trauma. Design, Setting, and Participants:This cohort study analyzes the data included in a multicenter national French trauma registry, Traumabase, from January 2012 to July 2017. Traumabase is a prospective, active, multicenter adult trauma registry that includes all consecutive patients with trauma treated at 15 trauma centers in France. Overall, 897 patients with severe bleeding after trauma were identified using the following criteria: (1) received 4 or more units of PRBC during the first 6 hours or (2) died from hemorrhagic shock before receiving 4 units of PRBC. Exposures:Eligible patients were divided into a high-ratio group, defined as an FFP-to-PRBC ratio more than 1:1.5, and a low-ratio group, defined as an FFP-to-PRBC ratio of 1:1.5 or less. The ratio was calculated using the cumulative units of FFP and PRBC received during the first 6 hours of management. Main Outcomes and Measures:A Cox regression model was used to analyze 30-day survival with the transfusion ratio as a time-dependent variable to account for survivorship bias. Results:Of the 12 217 patients included in the registry, 897 (7.3%) were analyzed (median [interquartile range] age, 38 (29-54) years; 639 [71.2%] men). The median (interquartile range) injury severity score was 34 (22-48), and the overall 30-day mortality rate was 33.6% (301 patients). A total of 506 patients (56.4%) underwent transfusion with a high ratio and 391 (43.6%) with a low ratio. A high transfusion ratio was associated with a significant reduction in 30-day mortality (hazard ratio, 0.74; 95% CI, 0.58-0.94; P = .01). When only analyzing patients who had complete data, a high transfusion ratio continued to be associated with a reduction in 30-day mortality (hazard ratio, 0.57; 95% CI, 0.33-0.97; P = .04). Conclusions and Relevance:In this analysis of the Traumabase registry, an early FFP-to-PRBC ratio of more than 1:1.5 was associated with increased 30-day survival among patients with severe bleeding after trauma. This result supports the use of early, high FFP-to-PRBC transfusion ratios in patients with severe trauma.
| S-EPMC6763975 | biostudies-literature
Project description:BackgroundExtracellular particles (EPs), particularly extracellular vesicles, play a crucial role in regulating various pathological mechanisms, including immune dysregulations post-trauma. Their distinctive expression of cell-specific markers and regulatory cargo such as cytokines or micro-ribonucleic acid suggests their potential as early biomarkers for organ-specific damage and for identifying patients at risk for complications and mortality. Given the critical need for reliable and easily assessable makers to identify at-risk patients and guide therapeutic decisions, we evaluated the early diagnostic value of circulating EPs regarding outcomes in severely injured multiple-trauma patients.MethodsPlasma samples were collected from 133 severely injured trauma patients (Injury Severity Score (ISS) ≥16) immediately upon arrival at the emergency department (ED). Patients were categorized into survivors and non-survivors. Injury characteristics and outcomes related to sepsis, pneumonia, or early (<1 day after admission) and late mortality were assessed. Circulating EPs, cytokine profiles, and blood counts of platelets and leukocytes were determined. Receiver operating characteristic analyses were conducted.ResultsDespite no significant differences in injury pattern or severity, non-survivors exhibited significantly elevated counts of circulating EPs compared to survivors. The optimal cut-off for EPs <200 nm indicating non-survivors was 17380/µl plasma, with a sensitivity of 77% and a specificity of 61% in predicting in-hospital mortality. Later non-survivors received significantly higher numbers of units of packed red blood cells [8.54 ± 5.45 vs. 1.29 ± 0.36 units], had higher serum lactate [38.00 ± 7.51 vs. 26.98 ± 1.58 mg/dL], significantly lower platelet counts [181.30 ± 18.06 vs. 213.60 ± 5.85 *10³/µL] and lower heart rates [74.50 ± 4.93 vs. 90.18 ± 2.06 beats/minute] upon arrival at the ED compared to survivors.ConclusionOur results demonstrate the high diagnostic potential of elevated concentrations of circulating EPs <200 nm for identifying patients at risk of mortality after severe trauma. This parameter shows comparable sensitivity to established clinical predictors. Early evaluation of EPs concentration could complement assessment markers in guiding early therapeutic decisions.
| S-EPMC11199388 | biostudies-literature
Project description:Background and Novel Aspect of this Work: In the light of previous findings that inflammation predisposes to intercellular adhesion and microvascular occlusion in sickle cell disease (SCD), this study investigated the relationship between the number of vaso-occlusive events in SCD, plasma levels of the pro-inflammatory molecules 12-Hydroxyeicosatetraenoic acid (12-HETE), TNF-α and IL-1β; and single nucleotide polymorphisms (SNPs) in the gene 12-Lipooxygenase (ALOX-12), which encodes the enzyme 12-Lipoxygenase that catalyzes the biosynthesis of 12-HETE. Objective: To evaluate the relationship between vaso-occlusion in SCD and plasma concentrations of 12-HETE, TNF-α, and IL-1β; and single nucleotide polymorphisms (SNPs) in ALOX-12 gene. Participants and Methods: In 50 HbSS patients, the numbers of vaso-occlusive crisis requiring hospital treatment in the previous 1 year and the vaso-occlusive complications of SCD developed to date (e.g stroke) were added to obtain the vaso-occlusive events (VOE) score. In the HbSS patients and 30 healthy sibling control persons, plasma concentrations of 12-HETE, TNF-α and IL-1β were measured by ELISA, the ALOX12 SNPs rs2073438 and rs1126667 detected by DNA sequencing, and the accrued data statistically analyzed. Results: Compared to SCD patients with VOE score 0-1, those with scores ≥3 had higher plasma levels of 12-HETE (p < 0.0001) and TNF-α (p = 0.19), but not IL-1β (p = 0.27). VOE score showed strong direct correlation with plasma level of 12-HETE (r = 0.65, p < 0.0001), but not with TNF-α nor IL-1β. Neither VOE score nor plasma concentration of 12-HETE showed any relationship with the ALOX12 SNPs rs2073438 and rs1126667. Conclusion: The strong direct correlation of VOE score with plasma concentration of 12-HETE suggests that the clinical relevance of this pro-inflammatory molecule in SCD-associated vaso-occlusion needs to be evaluated in further studies.
| S-EPMC8525407 | biostudies-literature
Project description:Here we recorded serum proteome profiles of 33 COVID-19 patients admitted to the ICU. We received, for most patients, blood samples just after admission and at two more later timepoints. We focused on serum proteins different in abundance between the group of survivors and non-survivors and observed that a rather small panel of about a dozen proteins were significantly different in abundance between these two groups. The four structurally and functionally related type-3 cystatins AHSG, FETUB, HRG and KNG1 were all more abundant in the survivors. The family of inter-α-trypsin inhibitors, ITIH1, ITIH2, ITIH3 and ITIH4, were all found to be differentially abundant in between survivors and non-survivors, whereby ITIH1 and ITIH2 were more abundant in the survivor group and ITIH3 and ITIH4 more abundant in the non-survivors. ITIH1/ITIH2 and ITIH3/ITIH4 also did show opposite trends in protein abundance during disease progression. This panel of eight proteins, complemented with a few more, may represent a panel for mortality risk assessment and eventually even for treatment, by administration of exogenous proteins possibly aiding survival. Such administration is not unprecedented, as administration of exogenous inter-α-trypsin inhibitors is already used in the treatment of patients with severe sepsis and Kawasaki disease. The mortality risk panel defined here is in excellent agreement with findings in two recent COVID-19 serum proteomics studies on independent cohorts, supporting our findings. This panel may not be unique for COVID-19, as some of the proteins here annotated as mortality risk factors have previously been annotated as mortality markers in aging and in other diseases caused by different pathogens, including bacteria.
2021-07-05 | PXD024707 | Pride
Project description:PurposeThoracic trauma accounts for 25-50% of posttraumatic mortality. Data on epidemiology of thoracic trauma in Scandinavia and risk factors for mortality are scarce. This study aims to provide an overview of epidemiology, clinical events and risk factors for mortality of patients with severe thoracic injuries.MethodsA retrospective study including adult thoracic trauma patients with abbreviated injury scale ≥ 3, between 2009 and 2018 at Haukeland University Hospital was performed. Subgroup analyses were performed for specific patient groups: (1) isolated thoracic trauma, (2) polytrauma without Traumatic Brain Injury (TBI) and (3) polytrauma with TBI. Logistic regression analyses were applied to find risk factors for 30-days mortality. Age, sex, comorbidity polypharmacy score (CPS), trauma and injury severity score (TRISS) and comprehensive complication index (CI) were included in the final model.ResultsData of 514 patients were analyzed, of which 60 (12%) patients died. Median (IQR) injury severity score (ISS) was 17 (13-27). Data of 463 patients, of which 39 patients died (8%), were included in multivariate analyses. Female sex odds ratio (OR) (2.7, p = 0.04), CPS > 9 (OR 4.8; p = 0.01), TRISS ≤ 50% (OR 44; p < 0.001) and CI ≥ 30 (OR 12.5, p < 0.001) were significant risk factors for mortality. Subgroup analyses did not demonstrate other risk factors.ConclusionComorbidities and associated pharmacotherapies, TRISS, female sex, and complications during admission predict in-hospital mortality after thoracic trauma. Current findings might help to recognize patients at risk of an adverse outcome, and thereby prevent complications.Trial registrationRETROSPECTIVELY REGISTERED: The regional committees for medical and health research ethics file number is 2017/293.
| S-EPMC10175434 | biostudies-literature
Project description:Background: Prehospital trauma triage tools are not tailored to identify severely injured older adults. Our trauma triage protocol based on a three-tier trauma severity grading system (A, B, and C) has never been studied in this population. The objective was to assess its accuracy in predicting in-hospital mortality among older adults (≥65 years) and to compare it to younger patients. Methods: A retrospective multicenter cohort study, from 2011 to 2021. Consecutive adult trauma patients managed by a mobile medical team were prospectively graded A, B, or C according to the initial seriousness of their injuries. Accuracy was evaluated using sensitivity, specificity, positive and negative predictive values, and positive and negative likelihood ratios. Results: 8888 patients were included (14.1% were ≥65 years). Overall, 10.1% were labeled Grade A (15.2% vs. 9.3% among older and younger adults, respectively), 21.9% Grade B (27.9% vs. 20.9%), and 68.0% Grade C (56.9% vs. 69.8%). In-hospital mortality was 7.1% and was significantly higher among older adults regardless of severity grade. Grade A showed lower sensitivity (50.5 (43.7; 57.2) vs. 74.6 (69.8; 79.1), p < 0.0001) for predicting mortality among older adults compared to their younger counterparts. Similarly, Grade B was associated with lower sensitivity (89.5 (84.7; 93.3) vs. 97.2 (94.8; 98.60), p = 0.0003) and specificity (69.4 (66.3; 72.4) vs. 74.6 (73.6; 75.7], p = 0.001) among older adults. Conclusions: Our prehospital trauma triage protocol offers high sensitivity for predicting in-hospital mortality including older adults.
| S-EPMC9916137 | biostudies-literature
Project description:BackgroundEfforts to improve pediatric trauma outcomes need detailed data, optimally collected at lowest cost, to assess processes of care. We developed a novel database by merging 2 national data systems for 5 pediatric trauma centers to provide benchmarking metrics for mortality and non-mortality outcomes and to assess care provided throughout the care continuum.Study designTrauma registry and Virtual Pediatric Systems, LLC (VPS) from 5 pediatric trauma centers were merged for children younger than 18 years discharged in 2013 from a pediatric ICU after traumatic injury. For inpatient mortality, we compared risk-adjusted models for trauma registry only, VPS only, and a combination of trauma registry and VPS variables (trauma registry+VPS). To estimate risk-adjusted functional status, we created a prediction model de novo through purposeful covariate selection using dichotomized Pediatric Overall Performance Category scale.ResultsOf 688 children included, 77.3% were discharged from the ICU with good performance or mild overall disability and 17.6% with moderate or severe overall disability or coma. Inpatient mortality was 5.1%. The combined dataset provided the best-performing risk-adjusted model for predicting mortality, as measured by the C-statistic, pseudo-R2, and Akaike Information Criterion, when compared with the trauma registry-only model. The final Pediatric Overall Performance Category model demonstrated adequate discrimination (C-statistic = 0.896) and calibration (Hosmer-Lemeshow goodness-of-fit p = 0.65). The probability of poor outcomes varied significantly by site (p < 0.0001).ConclusionsMerging 2 data systems allowed for improved risk-adjusted modeling for mortality and functional status. The merged database allowed for patient evaluation throughout the care continuum on a multi-institutional level. Merging existing data is feasible, innovative, and has potential to impact care with minimal new resources.
| S-EPMC6475528 | biostudies-literature
Project description:The incidence of pancreatic cancer increases with age, suggesting that chronological aging is a significant risk factor for this disease. Fibroblasts are the major nonmalignant cell type in the stroma of human pancreatic ductal adenocarcinoma (PDAC). In this study, we investigated whether the chronological aging of normal human fibroblasts (NHFs), a previously underappreciated area in pancreatic cancer research, influences the progression and therapeutic outcomes of PDAC. Results from experiments with murine xenografts and 2D and 3D co-cultures of NHFs and PDAC cells revealed that older NHFs stimulate proliferation of and confer resistance to radiation therapy of PDAC. MS-based metabolite analysis indicated that older NHFs have significantly increased arachidonic acid 12-lipoxygenase (ALOX12) expression and elevated levels of its mitogenic metabolite, 12-(S)-hydroxy-5,8,10,14-eicosatetraenoic acid (12-(S)-HETE) compared with their younger counterparts. In co-cultures with older rather than with younger NHFs, PDAC cells exhibited increases in mitogen-activated protein kinase signaling and cellular metabolism, as well as a lower oxidation state that correlated with their enhanced proliferation and resistance to radiation therapy. Expression of ALOX12 was found to be significantly lower in PDAC cell lines and tumor biopsies, suggesting that PDAC cells rely on a stromal supply of mitogens for their proliferative needs. Pharmacological (hydroxytyrosol) and molecular (siRNA) interventions of ALOX12 in older NHFs suppressed their ability to stimulate proliferation of PDAC cells. We conclude that chronological aging of NHFs contributes to PDAC progression and that ALOX12 and 12-(S)-HETE may be potential stromal targets for interventions that seek to halt progression and improve therapy outcomes.
| S-EPMC7242692 | biostudies-literature
Project description:The effect of 12-hydroxyeicosatetraenoic acid (12-HETE), an arachidonic acid metabolite of 12-lipoxygenase, to activate p21(Rac/Cdc42)-activated kinase (PAK1) was studied in a Chinese hamster ovary fibroblast cell line overexpressing the rat vascular type-1a angiotensin II receptor (CHO-AT(1a)). 12-HETE (0.1 microM) treatment induced a time-dependent activation of PAK1, with a peak effect at 10 min (335 +/- 16% of control; n=3, P<0.001). The stimulatory effect of 12-HETE on PAK1 activity was dose-dependent, with the maximal activation at 0.01 microM (350+/-15% of control; n=3, P<0.001). A PAK1 fragment encoding the Cdc42/Rac binding domain (amino acid residues 67-150 of hPAK1 termed PBD), was transfected into CHO-AT(1a) cells. PBD transfection markedly reduced 12-HETE-induced PAK1 activation. Furthermore, transfection of dominant negative Cdc42 and Rac1 inhibited 12-HETE-induced PAK1, strongly suggesting that Cdc42 and Rac1 are the upstream activators of 12-HETE-induced PAK1 activation. Low concentrations (1.5 microM) of LY294002, a highly specific inhibitor of phosphoinositide 3-kinase (PI-3K), abolished 12-HETE-induced PAK1 activation, suggesting that PI-3K activation is upstream of 12-HETE-induced PAK1 activation. Transfection of dominant negative PAK1 blocked 12-HETE-induced PAK1, cJun N-terminal kinase (JNK1) and extracellular-signal-regulated kinase (ERK) activity, while transfection of constitutively active PAK1 stimulated PAK1, JNK1 and ERK activity, suggesting that PAK1 is an upstream activator of 12-HETE-induced JNK1 and ERK activation in these cells. We conclude that 12-HETE can activate Cdc42, Rac1 and PI-3K, which then participate as upstream signalling molecules for PAK1 and JNK1 activation.
| S-EPMC1221171 | biostudies-other
Project description:BackgroundExtracellular vesicles (EV) released into the circulation after traumatic injury may influence complications. We thus evaluated the numbers of EV in plasma over 28 days after trauma and evaluated their pro-coagulant and inflammatory effects.Methods and findings37 patients suffering trauma with an injury severity score >15 were studied along with 24 healthy controls. Plasma samples were isolated by double centrifugation (2000g 20min; 13000g 2min) from blood collected from within an hour up to 28 days after injury. Plasma EV were counted and sized using nanoparticle tracking analysis (NTA); counts and cellular origins were also determined by flow cytometry (FC) using cell-specific markers. Functional effects were tested in a procoagulant phospholipid assay and in flow-based, leukocyte adhesion assay after endothelial cells (EC) were treated with EV. We found that EV concentrations measured by NTA were significantly increased in trauma patients compared to healthy controls, and remained elevated over days. In addition, or FC showed that patients with trauma had higher numbers of EV derived from platelets (CD41+), leukocytes (CD45+) and endothelial EC (CD144+). The increases were evident throughout the 28-day follow-up. However, the FC count represented <1% of the count detected by NTA, and only 1-2% of EV identified using NTA had a diameter >400nm. The procoagulant phospholipid activity assay showed that patient plasma accelerated coagulation on day 1 and day 3 after trauma, with coagulation times correlated with EV counts. Furthermore, treatment of EC for 24 hours with plasma containing EV tended to increase the recruitment of peripheral flowing blood mononuclear cells.ConclusionsEV counted by FC represent a small sub-population of the total load detected by NTA. Both methods however indicate a significant increase in plasma EV after severe traumatic injury that have pro-coagulant and pro-inflammatory effects that may influence outcomes.
| S-EPMC5570308 | biostudies-literature