Philipp Störmann

The effect of brain injury on the inflammatory response following severe trauma

INTRODUCTION The inflammatory response is an important part of the pathophysiology of severe injury and, in particular, of severe traumatic brain injury (TBI). This study evaluates the inflammatory course following major trauma and focuses on the effect of severe TBI on inflammatory markers. MATERIAL AND METHODS This was a retrospective analysis of prospectively collected data in 123 severely injured (ISS ≥16) trauma patients. The study cohort was divided into patients with isolated TBI (Head AIS ≥3, all other AIS <3), polytraumatized patients with severe TBI (Head AIS ≥3; AIS of other body area ≥3; Polytrauma+TBI) and polytraumatized patients without TBI (Head AIS <3; Polytrauma). Levels of inflammatory markers (Interleukin-6 [IL-6], C-reactive Protein [CRP], leukocytes) measured upon arrival and through hospital days 1-3 were compared between the groups. RESULTS On admission and through hospital day 3, IL-6 levels were significantly different between the 3 groups (admission: isolated TBI vs. Polytrauma+TBI vs. Polytrauma; 94±16 vs. 149±20 vs. 245±50pg/mL; p<0.05). Interleukin-6 levels peaked on hospital day 1 and declined thereafter. C-reactive protein and leukocyte counts were not significantly different between the cohorts on arrival and peaked on hospital day 2 and 1, respectively. In patients with severe TBI, admission IL-6 levels significantly predicted the development of septic complications (ROC analysis, AUC: 0.88, p=0.001, 95% CI: 0.79-0.97) and multiple organ dysfunction (ROC analysis, AUC: 0.83, p=0.001, 95% CI: 0.69-0.96). CONCLUSION Severe TBI reduced the inflammatory response following trauma. Significant correlations between admission IL-6 values and the development of MOF, sepsis and the neurological outcome were found in patients with TBI.

Alcohol intoxication reduces systemic interleukin-6 levels and leukocyte counts after severe TBI compared with not-intoxicated TBI patients

Background: The effect of alcohol consumption on inflammatory state and outcome in brain-injured patients remains controversial. We analyzed the influence of positive blood alcohol concentration (BAC) on inflammatory changes, inhospital complications, and mortality in traumatic brain injury (TBI) patients. Patients and Methods: Patients with an Injury Severity Score (ISS) at least 16 and Abbreviated Injury Scale of head (AIS-head) at least 3 were included upon arrival in the emergency room and grouped according to positive BAC (>0.5‰, BAC) vs. less than 0.5‰ alcohol (no BAC). Injury severity, vital signs, complications, mortality, and systemic interleukin (IL)-6 levels were prospectively determined, and BAC was quantified. According to ISS, AIS-head, age, and sex, we performed matched-pair analysis. Results: A total of 101 TBI patients were included. Of them 74 patients were dedicated to no BAC group and 27 to BAC group. ISS was significantly higher in the no BAC group. Positive BAC group required significantly less packed red blood cells and fresh frozen plasma (P < 0.05). Shorter ICU stays were found in BAC-positive patients. Inhospital complications, including single/multiple organ failure, systemic inflammatory response syndrome, sepsis, pneumonia, and acute respiratory distress syndrome, showed no significant differences. Systemic IL-6 levels and leukocyte counts (IL-6: 65.0 ± 8.0 vs. 151.8 ± 22.3; leukocytes: 10.2 ± 0.9 vs. 13.2 ± 0.8, both P < 0.05) were significantly lower in BAC-positive patients. Matched-pair analysis was performed with 27 pairs. No significant differences in transfusions were monitored after matching. However, lowered systemic IL-6 levels and leukocyte counts in the BAC group were also detected after matching, indicating that this effect is ISS-independent. Conclusions: This study shows that positive BAC in TBI patients is associated with lower systemic IL-6 levels and leukocyte numbers, indicating that positive BAC may have immunosuppressive effects in this cohort of patients compared with TBI patients who were not alcohol intoxicated.

Influence of gender on systemic IL-6 levels, complication rates and outcome after major trauma

BACKGROUND While female gender was associated with lower rates of systemic inflammatory response syndrome (SIRS), sepsis and single and/or multiple organ failure (MOF), contradictory data suggest no correlation between gender and complication rates and/or outcome in trauma patients (TP). Here, we analyzed the gender influence on systemic interleukin (IL)-6 levels and outcome in TP. PATIENTS/METHODS 343 TP with injury severity scores (ISS) ≥16 were included upon admittance to the emergency department (ED) and grouped to male (n=257) vs. female (n=86). Injury severity, vital signs, physiological parameters, length of intensive care unit (ICU) and in-hospital stay, outcome parameters including SIRS, sepsis, respiratory complications, single- and/or MOF and in-hospital mortality were analyzed. Systemic IL-6 levels during the first 10 post-injury days were determined daily. RESULTS Age (45.0±1.0 vs. 48.2±2.1) and ISS (27.1±0.8 vs. 24.7±1.2) were comparable between both groups. Abbreviated Injury Scale (AIS) ≥3 of chest and abdominal body regions were significantly higher in male TP (chest:51.02% vs. 36.05%, abdomen:19.84% vs. 10.47%, p<0.05). IL-6 was significantly increased in male TP on post-injury days 1 and 2 (d1:363.9±72.58 vs. 163.7±25.98; d2:194.3±31.38 vs. 114.3±17.81pg/ml, p<0.05). Multivariate analysis excluded an association of increased chest or abdominal injury occurrence with IL-6 levels. Female vs. male TP had significantly lower SIRS and sepsis occurrence (SIRS:40.70% vs. 53.31%, sepsis:6.98% vs. 19.46%, p<0.05). There were no gender-based differences regarding ICU or in-hospital stay, single and/or MOF and respiratory complications. CONCLUSIONS Taken together, higher systemic IL-6 levels after trauma are associated with enhanced susceptibility for SIRS and sepsis in male patients.

Characterization of blunt chest trauma in a long-term porcine model of severe multiple trauma

Chest trauma has a significant relevance on outcome after severe trauma. Clinically, impaired lung function typically occurs within 72 hours after trauma. However, the underlying pathophysiological mechanisms are still not fully elucidated. Therefore, we aimed to establish an experimental long-term model to investigate physiological, morphologic and inflammatory changes, after severe trauma. Male pigs (sus scrofa) sustained severe trauma (including unilateral chest trauma, femur fracture, liver laceration and hemorrhagic shock). Additionally, non-injured animals served as sham controls. Chest trauma resulted in severe lung damage on both CT and histological analyses. Furthermore, severe inflammation with a systemic increase of IL-6 (p = 0.0305) and a local increase of IL-8 in BAL (p = 0.0009) was observed. The pO2/FiO2 ratio in trauma animals decreased over the observation period (p < 0.0001) but not in the sham group (p = 0.2967). Electrical Impedance Tomography (EIT) revealed differences between the traumatized and healthy lung (p < 0.0001). In conclusion, a clinically relevant, long-term model of blunt chest trauma with concomitant injuries has been developed. This reproducible model allows to examine local and systemic consequences of trauma and is valid for investigation of potential diagnostic or therapeutic options. In this context, EIT might represent a radiation-free method for bedside diagnostics.

Decreased Inflammatory Responses of Human Lung Epithelial Cells after Ethanol Exposure Are Mimicked by Ethyl Pyruvate

Background and Purpose. Leukocyte migration into alveolar space plays a critical role in pulmonary inflammation resulting in lung injury. Acute ethanol (EtOH) exposure exerts anti-inflammatory effects. The clinical use of EtOH is critical due to its side effects. Here, we compared effects of EtOH and ethyl pyruvate (EtP) on neutrophil adhesion and activation of cultured alveolar epithelial cells (A549). Experimental Approach. Time course and dose-dependent release of interleukin- (IL-) 6 and IL-8 from A549 were measured after pretreatment of A549 with EtP (2.5–10 mM), sodium pyruvate (NaP, 10 mM), or EtOH (85–170 mM), and subsequent lipopolysaccharide or IL-1beta stimulation. Neutrophil adhesion to pretreated and stimulated A549 monolayers and CD54 surface expression were determined. Key Results. Treating A549 with EtOH or EtP reduced substantially the cytokine-induced release of IL-8 and IL-6. EtOH and EtP (but not NaP) reduced the adhesion of neutrophils to monolayers in a dose- and time-dependent fashion. CD54 expression on A549 decreased after EtOH or EtP treatment before IL-1beta stimulation. Conclusions and Implications. EtP reduces secretory and adhesive potential of lung epithelial cells under inflammatory conditions. These findings suggest EtP as a potential treatment alternative that mimics the anti-inflammatory effects of EtOH in early inflammatory response in lungs.

Role of biomarkers in acute traumatic lung injury

In severely injured patients severe thoracic trauma is common and can significantly influence the outcome of these critically ill patients by increased rates of mainly pulmonary complications. Furthermore, patients who sustained thoracic trauma are at increased risk for Acute Lung Injury (ALI) or Adult Respiratory Distress Syndrome (ARDS). Therapeutic options are limited, basically consisting of prophylactic antibiotic therapy and changing patients positions. It is known, that ALI and ARDS differ clinically and pathobiologically from ALI/ARDS caused by other reasons, but the exact pathology remains elusive. Due to that no reliable predictive or surveillance biomarkers could be established for clinical diagnosis and identification of patients at high risk for acute traumatic lung injury. Nevertheless, there are plenty of promising markers that need to be further elucidated in larger case numbers and multicenter studies. This article sums up the recent status of those promising clinical biomarkers.

The Role of Pelvic Packing for Hemodynamically Unstable Pelvic Ring Injuries

In patients with severe pelvic fractures, exsanguinating hemorrhage represents the major cause of death within the first 24 hours. Recently, multiple management algorithms have been proposed; however, the optimal treatment modalities, in particular, in the hemodynamically unstable patient with pelvic fracture are still a matter of debate. Mechanical pelvic stabilization by pelvic binder, anterior external fixator, and/or pelvic C-clamp constitutes the first treatment option in the hemodynamically unstable patient with pelvic fractures. The mechanically stabilized pelvic ring provides the basis for pelvic packing through a minimal extraperitoneal approach, which effectively controls venous bleeding and bleeding from the fractured bony surface. Patients with persistent hypotension and/or transfusion requirements should undergo angiography and selective embolization for definitive arterial control if necessary. This review article describes the current trend in the initial management of patients with pelvic fractures and hemodynamic instability, and focuses on the role of pelvic packing.

Comparative Analysis of the Regulatory T Cells Dynamics in Peripheral Blood in Human and Porcine Polytrauma

Background Severely injured patients experience substantial immunological stress in the aftermath of traumatic insult, which often results in systemic immune dysregulation. Regulatory T cells (Treg) play a key role in the suppression of the immune response and in the maintenance of immunological homeostasis. Little is known about their presence and dynamics in blood after trauma, and nothing is known about Treg in the porcine polytrauma model. Here, we assessed different subsets of Treg in trauma patients (TP) and compared those to either healthy volunteers (HV) or data from porcine polytrauma. Methods Peripheral blood was withdrawn from 20 TP with injury severity score (ISS) ≥16 at the admittance to the emergency department (ED), and subsequently on day 1 and at day 3. Ten HV were included as controls (ctrl). The porcine polytrauma model consisted of a femur fracture, liver laceration, lung contusion, and hemorrhagic shock resulting in an ISS of 27. After polytrauma, the animals underwent resuscitation and surgical fracture fixation. Blood samples were withdrawn before and immediately after trauma, 24 and 72 h later. Different subsets of Treg, CD4+CD25+, CD4+CD25+FoxP3+, CD4+CD25+CD127−, and CD4+CD25+CD127−FoxP3+ were characterized by flow cytometry. Results Absolute cell counts of leukocytes were significantly increasing after trauma, and again decreasing in the follow-up in human and porcine samples. The proportion of human Treg in the peripheral blood of TP admitted to the ED was lower when compared to HV. Their numbers did not recover until 72 h after trauma. Comparable data were found for all subsets. The situation in the porcine trauma model was comparable with the clinical data. In porcine peripheral blood before trauma, we could identify Treg with the typical immunophenotype (CD4+CD25+CD127−), which were virtually absent immediately after trauma. Similar to the human situation, most of these cells expressed FoxP3, as assessed by intracellular FACS stain. Conclusion Despite minor percental differences in the recovery of Treg populations after trauma, our findings show a comparable decrease of Treg early after polytrauma, and strengthen the immunological significance of the porcine polytrauma model. Furthermore, the Treg subpopulation CD4+CD25+CD127− was characterized in porcine samples.

Characteristics and management of penetrating abdominal injuries in a German level I trauma center

PurposePenetrating abdominal injuries caused by stabbing or firearms are rare in Germany, thus there is lack of descriptive studies. The management of hemodynamically stable patients is still under dispute. The aim of this study is to review and improve our management of penetrating abdominal injuries.MethodsWe retrospectively reviewed a 10-year period from the Trauma Registry of our level I trauma center. The data of all patients regarding demographics, clinical and outcome parameters were examined. Further, charts were reviewed for FAST and CT results and correlated with intraoperative findings.ResultsA total of 115 patients with penetrating abdominal trauma (87.8% men) were analyzed. In 69 patients, the injuries were caused by interpersonal violence and included 88 stab and 4 firearm wounds. 8 patients (6.9%) were in a state of shock at presentation. 52 patients (44.8%) suffered additional extraabdominal injuries. 38 patients were managed non-operatively, while almost two-thirds of all patients underwent surgical treatment. Hereof, 20 laparoscopies and 3 laparotomies were nontherapeutic. There were two missed injuries, but no patient experienced morbidity or mortality related to delay in treatment. 106 (92.2%) FAST and 91 (79.3%) CT scans were performed. Sensitivity and specificity of FAST were 59.4 and 94.2%, while those of CT were 93.2 and 85.1%, respectively.ConclusionIn hemodynamically stable patients presenting with penetrating abdominal trauma, CT is indicated and the majority of injuries can be managed conservatively. If surgical treatment is required, diagnostic laparoscopy for stable patients is feasible to avoid nontherapeutic laparotomy.

Cultivation of EPC and co-cultivation with MSC on β-TCP granules in vitro is feasible without fibronectin coating but influenced by scaffolds’ design

IntroductionMeanwhile, the osteoconductive properties of frequently used synthetic bone grafts can be improved by the use of osteoinductive cells and growth factors. Nevertheless, the cultivation of endothelial progenitor cells (EPC) seems to be difficult and requires a pre-conditioning of the scaffolds with fibronectin. Additionally, the influence of the scaffolds’ design on cell cultivation is not fully elucidated.MethodsAs scaffold, a commercially available β-tricalcium phosphate was used. 5 × 105 EPC, or 5 × 105 MSC or a combination of each 2.5 × 105 cells was seeded onto the granules. We investigated seeding efficiency, cell morphology, cell metabolism, adherence, apoptosis and gene expression of EPC and MSC in this in vitro study on days 2, 6 and 10.ResultsTotal number of adherent cells was higher on the β-TCP without fibronectin coating. The number of cells in all approaches significantly declined when a solid β-TCP was used. Metabolic activity of MSC was comparable throughout the scaffolds and increased until day 10. Additionally, the amount of supernatants VEGF was higher for MSC than for EPC.DiscussionOur results demonstrate that a coating of the scaffold for successful cultivation of EPC in vitro is not necessary. Furthermore, our study showed that structural differences of the scaffolds significantly influenced cell adherence and metabolic activity. Thereby, the influence on EPC seems to be higher than on MSC.