Neutrophil Gene Expression Patterns in Multiple Trauma Patients Indicate Distinct Clinical Outcomes.

INTRODUCTION: Patients after polytrauma suffer from posttraumatic immune system dysregulation and multiple organ dysfunction. Genome-wide microarray profiling in monocytes revealed a regulatory network of inflammatory markers around the transcription factor AP-1 in severely injured patients. Recent research focuses on the role of neutrophils in posttraumatic inflammation. The aim of this study was, therefore, to evaluate the impact of this inflammatory network in neutrophils. MATERIALS AND METHODS: Blood sampling and neutrophil separation were performed on admission of the patient and at 6 h, 12 h, 24 h, 48 h, and 72 h after trauma. Neutrophil expression levels of the target genes c-Jun, c-Fos, BCL2A, MMP-9, TIMP-1, ETS-2, IL-1ß, and MIP-1ß were quantified by RT-qPCR. Patients were assorted into groups according to distinct clinical parameters like massive transfusion (>10 RBC units/24 h), injury severity (ISS), 90-d survival, and the presence of traumatic brain injury (defined by ICI on head CT). Statistics were calculated by Mann-Whitney Rank-Sum Test, Receiver Operating Curves, and binary multiple logistic regression. RESULTS: Forty severely injured patients (mean ISS 36 ± 14) were included. BCL2A, MMP-9, TIMP-1, and ETS2 levels showed a significant correlation to 90-d-survival in the early posttraumatic period (6 h-24 h). Furthermore, differential BCL2A, IL-1ß, MIP-1ß, and MMP-9 regulation was observed in patients requiring massive transfusion. We could further show a significant TIMP-1 response in trauma PMN associated with traumatic brain injury. CONCLUSIONS: This study of seriously injured patients highlights very early posttraumatic transcriptional changes in PMNs, which were clearly associated with posttraumatic events and outcomes.

Radiological Outcome Measures Indicate Advantages of Precontoured Locking Compression Plates in Elderly Patients With Split-Depression Fractures to the Lateral Tibial Plateau (AO41B3).

BACKGROUND: Split-depression fractures to the lateral tibial plateau (AO41B3) often feature severe joint surface destructions. Precontoured locking compression plates (LCPs) are designed for optimum support of the reduced joint surface and have especially been emphasized in reduced bone quality. A lack of evidence still inhibits their broad utilization in elderly patients. Thus, aim of the present study was to investigate the implant-specific radiological outcomes of AO41B3-fractures in young versus elderly patients. METHODS: The hospital's database was screened for isolated AO41B3-factures, open reduction and internal fixation (ORIF), and radiological follow-up ≥12 months. CT-scans, radiographs, and patients' records were analyzed. Patients were attributed as young (18-49) or elderly (≥50 years). Additional subgrouping was carried out into precontoured LCP and conventional implants. The Rasmussen Radiological Score (RRS) after 12 months was set as primary outcome parameter. The RRS postoperatively and the medial proximal tibial angle (MPTA) postoperatively and after 12 months were secondary outcome parameters. RESULTS: Fifty nine consecutive patients were included (26 young, 38.2 ± 7.8 years; 33 elderly, 61.3 ± 9.4 years). There were no significant differences regarding mean size and depression depth of the lateral joint surface fragments. Prior to implant-specific subgrouping, the radiological outcome measures revealed no significant differences between young (RRS = 7.7 ± 1.7; MPTA = 90.3 ± 2.3°) and elderly (RRS = 7.2 ± 1.7; MPTA = 90.5 ± 3.3°). After implant-specific subgrouping, the radiological outcome revealed significantly impaired results in young patients with conventional implants (RRS(C) = 6.9 ± 1.6, RRS(LCP) = 8.5 ± 1.5, P = .015; MPTA(C) = 91.5 ± 1.9°, MPTA(LCP) = 89.1 ± 2.1°, P = .01). The effect was even more pronounced in elderly patients, with highly significant deterioration of the radiological outcome measures for conventional implants compared to precontoured LCP (RRS(C) = 5.7 ± 1.6, RRS(LCP) = 8.2 ± .8, P < .001; MPTA(C) = 92.6 ± 4.2°, MPTA(LCP) = 89.2 ± 1.4°, P = .002). CONCLUSION: Utilizing precontoured LCP in the treatment of AO41B3-fractures is associated with improved radiological outcomes. This effect is significant in young but even more pronounced in elderly patients. Consequently, precontoured LCP should closely be considered in any AO41B3-fracture, but especially in elderly patients.

Polytrauma in Older Adults Leads to Significantly Increased TIMP-1 Levels in the Early Posttraumatic Period.

BACKGROUND: Patients after polytrauma regularly suffer from posttraumatic immune system destabilization, which closely influences the further clinical development. Increasing age has recently been identified as an isolated risk factor for an adverse outcome after major trauma. Higher rates and intensity of acute inflammation following severe injury suggest that deregulated inflammation may contribute to these higher rates of posttraumatic morbidity and mortality in older adults. MMP-9 and TIMP-1 have been found to play a major role in posttraumatic immune disorder in a previous genome-wide mRNA analysis. OBJECTIVE: The aim of this study was to evaluate the differences in serum protein dynamics in older and younger polytraumatized adults. METHODS: Blood samples were drawn immediately within 90 minutes after trauma and subsequently after 6, 12, 24, 48, and 72 h. Serum levels of TIMP-1 and MMP-9 were quantified using ELISA. Age groups were divided according to a cutoff of 60 years. RESULTS: 60 polytrauma patients (ISS > 16) were included (<60 years, n = 49; ≥60 years, n = 49; ≥60 years, n = 11). Serum TIMP-1 and MMP-9 levels showed a highly significant serum dynamic in young and old polytrauma patients (p < 0.001). Patients ≥ 60 years showed significantly higher overall TIMP-1 levels (p < 0.001). Patients ≥ 60 years showed significantly higher overall TIMP-1 levels (p = 0.008). TIMP-1 levels showed a significant maximum after 72 h in the older study population. MMP-9 levels were nonsignificantly higher during the whole observational period in older polytrauma patients when compared to younger patients. CONCLUSION: The posttraumatic immune response is characterized by significantly higher TIMP-1 levels in older polytrauma patients. This significant association between TIMP-1 levels and patients' age indicates a more extensive immune dysregulation following major trauma in older adults.

Selenium and Selenoprotein P Deficiency Correlates With Complications and Adverse Outcome After Major Trauma.

BACKGROUND: A declining selenium (Se) status constitutes a characteristic of critical illness and may affect disease course and survival. The dynamics of trauma-induced changes in biomarkers of Se status are poorly characterized, and an association with multiple organ failure (MOF) and mortality can be hypothesized. It was the aim of this study to investigate Se and selenoprotein P (SELENOP) concentrations in major trauma patients during the early posttraumatic period. PATIENTS AND METHODS: Twenty-four patients after major trauma (ISS ≥16) were included at our level one trauma center. Se supplementation ever during the 90-day observation period was defined as an exclusion criterion. Serum samples were drawn within less than 60 min after trauma, and after 6 h, 12 h, 24 h, 48 h, and 72 h. Serum Se was analyzed by X-ray fluorescence and SELENOP concentrations by ELISA. The data were correlated to clinical parameters, occurrence of MOF defined by MOF and APACHE II score, lung injury defined by Horowitz index and clinical outcome (90-days survival). RESULTS: Serum Se and SELENOP concentrations of the trauma patients were significantly below the average of healthy European subjects (mean ±SD; Se, 41.2±8.1 vs. 84.7±23.3 µg/L, P < 0.001; SePP, 1.5±0.3 vs. 4.3±1.0 mg/L, P < 0.001). A strong deficit was present already at the first time point (Se; 33.6±10.5 µg/L, SELENOP: 1.4±0.5 mg/L). The clinical scores collectively showed an inverse relation between health status and Se biomarkers. Patients who did not survive the 90-day observation period exhibited significantly lower initial post-trauma Se status than the surviving patients (mean±SD; Se, 24.7±7.2 vs. 39.2±8.4 µg/L, P<0.05; SePP, 1.1±0.4 vs. 1.6±0.4 mg/L, P<0.05). CONCLUSION: Very low Se and SELENOP concentrations occur fast after major trauma and are associated with poor survival odds. These findings support the notion that early Se substitution may constitute a meaningful adjuvant treatment strategy in trauma patients.

Significant Cytokine mRNA Expression Changes Immediately after Initiation of Cardiopulmonary Resuscitation.

INTRODUCTION: The purpose of this study was to evaluate immediate immunological changes following cardiopulmonary resuscitation (CPR). mRNA expression levels of selected immunomodulatory cytokines in out-of-hospital cardiac arrest (OHCA) survivors were detected and correlated to clinical parameter. METHODS: OHCA survivors with sustained unconsciousness after return of spontaneous circulation (ROSC) were included. PAXgene whole blood samples were drawn immediately after initiation of CPR and subsequently after 6 h, 12 h, 24 h, 48 h, and 72 h. TNF-alpha, IL-8, IL-10, and IL-1ra mRNA levels were quantified by RT-qPCR and compared to multiple organ failure, 30-day survival, and the induction of therapeutic hypothermia (TH). RESULTS: 25 patients (63 ± 15 years) were enrolled presenting a characteristic time-dependent cytokine profile in the early postresuscitation period. High initial TNF-alpha and IL-8 mRNA levels were followed by a significant decrease. IL-1ra mRNA levels significantly increased beginning after 6 h. Nonsurvivors showed significantly higher IL-8 mRNA levels immediately after CPR. TH induced significantly higher IL-1ra mRNA levels compared to normothermia. CONCLUSION: Significant mRNA cytokine expression changes are already detectable immediately after initiation of CPR. These expressional changes are significantly different depending on 30-day survival. TH seems to attenuate proinflammatory immune reaction by a significant increase of IL-1ra mRNA levels. This trial is registered with DRKS00012940.