Initial free cortisol dynamics following blunt multiple trauma and traumatic brain injury: A clinical study.

OBJECTIVE: To determine free and total cortisol serum concentrations in the first 24 h after trauma and to evaluate the influence of traumatic brain injury (TBI) on their dynamics. METHODS: This prospective cohort study enrolled patients who had experienced multiple trauma and were admitted to a level 1 trauma centre. The patients were divided in two groups based on the presence of TBI according to clinical and radiological findings. Blood was collected initially as well as at 12 h and 24 h after the traumatic injury. Total cortisol, corticosteroid binding globulin (CBG) and free cortisol levels were determined. RESULTS: The study analysed data from 49 patients (36 males and 13 females) with a mean ± SD age of 45.0 ± 16.0 years. Of these, 36 presented with TBI and 13 had multiple injuries without TBI. Patients with TBI showed significantly lower concentrations of total cortisol and free cortisol compared with patients without TBI. Repeated measures analysis revealed different concentration dynamics in patients with TBI, with no increase in cortisol after trauma. CONCLUSION: Multiple trauma patients with TBI are at risk of acute impaired cortisol secretion and show an attenuated stress response as early as 12 h after injury.

[Retrospective computation of the ISS in multiple trauma patients: Potential pitfalls and limitations of findings in full body CT scans]. / Retrospektive Berechnung des ISS bei polytraumatisierten Patienten: Fehlerquellen und Anforderungen an den radiologischen Befund der Ganzkörper-CT.

INTRODUCTION: The Injury Severity Score (ISS) is a well-established anatomical scoring system for polytraumatized patients. However, any inaccuracy in the Abbreviated Injury Score (AIS) directly increases the ISS impreciseness. Using the full body computed tomography (CT) scan report, ISS computation can be associated with certain pitfalls. This study evaluates interpretation variations depending on radiological reports and indicates requirements to reliably determine the ISS. MATERIALS AND METHODS: The ISS of 81 polytraumatized patients was calculated based on the full body CT scan report. If an injury could not be attributed to a precise AIS cipher, the minimal and maximal ISS was computed. Real ISS included all conducted investigations, intraoperative findings, and final medical reports. The differences in ISS min, ISS max, and ISS real were evaluated using the Kruskal-Wallis test (p<0.05) and plotted in a linear regression analysis. RESULTS: Mean ISS min was 24.0 (± 0.7 SEM) points, mean ISS real 38.6 (±1.3 SEM) and mean ISS max was 48.3 (±1.4 SEM) points. All means were significantly different compared to one another (p<0.001). The difference between possible and real ISS showed a distinctive variation. Mean deviation was 9.7 (±0.9 SEM) points downward and 14.5 (±1.1 SEM) points upward. The difference between deviation to ISS min and ISS max was highly significant (p<0.001). CONCLUSION: Objectification of injury severity in polytraumatized patients using the ISS is an internationally well-established method in clinical and scientific settings. The full body CT scan report must meet distinct criteria and has to be written in acquaintance to the AIS scale if intended to be used for correct ISS computation.

[Mild head injury in children and adults: Diagnostic challenges in the emergency department]. / Leichtes Schädel-Hirn-Trauma bei Kindern und Erwachsenen: Diagnostische Herausforderungen in der Notfallaufnahme.

Mild head injuries are one of the most frequent reasons for attending emergency departments and are particularly challenging in different ways. While clinically important injuries are infrequent, delayed or missed injuries may lead to fatal consequences. The initial mostly inconspicuous appearance may not reflect the degree of intracranial injury and computed tomography (CT) is necessary to rule out covert injuries. Furthermore, infants and young children with a lack of or rudimentary cognitive and language development are challenging, especially for those examiners not familiar with pediatric care. Established check lists of clinical risk factors for children and adults regarding traumatic brain injuries allow specific and rational decision-making for cranial CT imaging. Clinically important intracranial injuries can be reliably detected and unnecessary radiation exposure avoided at the same time.

[Mild head injury in children and adults. Diagnostic challenges in the emergency department]. / Leichtes Schädel-Hirn-Trauma bei Kindern und Erwachsenen. Diagnostische Herausforderungen in der Notfallaufnahme.

Mild head injuries are one of the most frequent reasons for attending emergency departments and are particularly challenging in different ways. While clinically important injuries are infrequent, delayed or missed injuries may lead to fatal consequences. The initial mostly inconspicuous appearance may not reflect the degree of intracranial injury and computed tomography (CT) is necessary to rule out covert injuries. Furthermore, infants and young children with a lack of or rudimentary cognitive and language development are challenging, especially for those examiners not familiar with pediatric care. Established check lists of clinical risk factors for children and adults regarding traumatic brain injuries allow specific and rational decision-making for cranial CT imaging. Clinically important intracranial injuries can be reliably detected and unnecessary radiation exposure avoided at the same time.

[Posttraumatic adhesive ileus following pelvic ring fracture]. / Posttraumatischer Briden-Ileus nach Beckenringfrakturen.

We report on two cases of posttraumatic ileus after pelvic ring fracture in two patients aged 73 and 74 years, respectively. Although all conservative measures were exhausted, in both cases the ileus resulted in additional operative procedures and a significant extension of the hospital stay. Intraoperatively both patients presented with a mechanical ileus caused by adhesions which were unapparent for decades. Only the trauma-related motility disorder led to a clinical manifestation. Pathophysiological mechanisms and their implications on prophylaxis and therapy are discussed.

[Microarrays as biomarkers in trauma]. / Microarrays als Biomarker nach Trauma.

BACKGROUND: The traditional hypothesis-driven scientific approach cannot so far sufficiently elucidate complex pathophysiologies, such as posttraumatic systemic inflammation and subsequent multiple organ failure. This complex system includes different biological and functional levels, the genome, the transcriptome, the proteome, the biome (cells), the organs and finally the whole organism. METHODS: Microarray techniques enable a simultaneous search for these different biological levels and their functional relationships on a large scale and to discover new functional pathways and networks and potentially new biomarkers for different pathologies. Microarray technologies lead to a new paradigm in science, the hypothesis-generating approach. AIM: This article reviews important microarray findings in trauma and systemic inflammation research and discusses potentials and limitations of these biotechnological screening methods.

Impact of STAT/SOCS mRNA expression levels after major injury.

BACKGROUND: Fulminant changes in cytokine receptor signalling might provoke severe pathological alterations after multiple trauma. The aim of this study was to evaluate the posttraumatic imbalance of the innate immune system with a special focus on the STAT/SOCS family. METHODS: 20 polytraumatized patients were included. Blood samples were drawn 0 h-72 h after trauma; mRNA expression profiles of IL-10, STAT 3, SOCS 1, and SOCS 3 were quantified by qPCR. RESULTS: IL-10 mRNA expression increased significantly in the early posttraumatic period. STAT 3 mRNA expressions showed a significant maximum at 6 h after trauma. SOCS 1 levels significantly decreased 6 h-72 h after trauma. SOCS 3 levels were significantly higher in nonsurvivors 6 h after trauma. CONCLUSION: We present a serial, sequential investigation in human neutrophil granulocytes of major trauma patients evaluating mRNA expression profiles of IL-10, STAT 3, SOCS 1, and SOCS 3. Posttraumatically, immune disorder was accompanied by a significant increase of IL-10 and STAT 3 mRNA expression, whereas SOCS 1 mRNA levels decreased after injury. We could demonstrate that death after trauma was associated with higher SOCS 3 mRNA levels already at 6 h after trauma. To support our results, further investigations have to evaluate protein levels of STAT/SOCS family in terms of posttraumatic immune imbalance.

Concentration kinetics of serum MMP-9 and TIMP-1 after blunt multiple injuries in the early posttraumatic period.

Metalloproteinases are secreted in response to a variety of inflammatory mediators and inhibited by tissue inhibitors of matrixmetalloproteinases (TIMPs). Two members of these families, MMP-9 and TIMP-1, were differentially expressed depending on clinical parameters in a previous genomewide mRNA analysis. The aim of this paper was now to evaluate the posttraumatic serum levels and the time course of both proteins depending on distinct clinical parameters. 60 multiple traumatized patients (ISS > 16) were included. Blood samples were drawn on admission and 6 h, 12 h, 24 h, 48 h, and 72 h after trauma. Serum levels were quantified by ELISA. MMP-9 levels significantly decreased in the early posttraumatic period (P < 0.05) whereas TIMP-1 levels significantly increased in all patients (P < 0.05). MMP-9 and TIMP-1 serum concentration kinetics became manifest in an inversely proportional balance. Furthermore, MMP-9 presented a stronger decrease in patients with severe trauma and non-survivors in contrast to minor traumatized patients (ISS ≤ 33) and survivors, initially after trauma.

[Treatment results after cemented hemiprosthesis for care of unstable pertrochanteric femoral fractures in the elderly]. / Behandlungsergebnisse nach zementierter Hemiprothese zur Versorgung instabiler pertrochantärer Femurfrakturen alter Patienten.

BACKGROUND: The optimal treatment strategy for unstable trochanteric fractures in the elderly is still controversial because of the frequent failure of osteosynthesis. METHODS: A cohort of patients with unstable trochanteric fractures who were treated with cemented hemiarthroplasty and presented in our department during the period 2003-2009 was analyzed. Complications, reoperations, walking ability and full weight bearing were documented. RESULTS: A total of 91 patients were included (mean age 87.7±6.8 years) and predominantly 31A2 fractures (89%) were treated. There were 3.3% reoperations in the cohort and the 30 day mortality was 5.5%. At least 1 general complication occurred in over 50% of the patients. However, 30% of the patients had lower urinary tract infections, disturbances of electrolyte balance or transitory psychotic symptoms. On average full weight bearing could be performed at 3.5 (±3) days after the operation. CONCLUSION: Cemented hemiarthroplasty is a safe treatment strategy for unstable trochanteric fractures in the elderly, which allows early full weight bearing. Because of frequent general complications, more interdisciplinary units and centres of excellence are needed to handle this challenging cohort.

[Serological determination of protein S100B. Significance in emergency diagnosis of adults with mild craniocerebral trauma--meta-analysis]. / Das serologische Protein S100B. Stellenwert in der Notfalldiagnostik Erwachsener mit Verdacht auf leichtes Schädel-Hirn-Trauma--eine Metaanalyse.

OBJECTIVE: Patients presenting in the emergency department with a mild injury to the head pose a particular challenge due to their high prevalence but low rate of traumatic brain injury. However, missed traumatic brain injuries may result in fatal consequences. Therefore we investigated the diagnostic performance of serological protein S100B measurement in adult patients presenting with mild head injury and a GCS 13-15 to identify traumatic brain injury. DESIGN AND METHODS: We conducted a systematic review of the literature. Two reviewers screened potential studies for inclusion and independently extracted study data. For all included studies, we applied the QUADAS quality assessment tool for systematic reviews of diagnostic accuracy and abstracted the raw data for every included study. Included studies presented results either in 2x2 contingency tables or provided data allowing their construction. RESULTS: Of 76 studies identified, 8 met the inclusion criteria. Methodology quality was moderate and all studies fulfilled at least 50% of the QUADAS criteria. Overall, the sensitivity to detect intracranial lesions was 94% (95% CI 88-98%) and specificity was 44% (95% CI 30-58%). The subgroup analysis showed significant differences only between studies with different S100B cutoff values (0.10 µg/l versus >0.10 µg/l). The combined odds ratio was 10.3 (95 CI 4.2-24.9). CONCLUSIONS: Serological protein S100B measurement may be helpful as a screening test to identify patients with higher risk of traumatic brain injury for further diagnostic assessment.

Very early posttraumatic serum alterations are significantly associated to initial massive RBC substitution, injury severity, multiple organ failure and adverse clinical outcome in multiple injured patients.

BACKGROUND: Multiple severe trauma frequently leads to massive dysbalances of the human immune system. This phenomenon is known as "Systemic Inflammatory Response Syndrome (SIRS)". SIRS is connected to multiple organ failure and thereby entails higher morbidity and mortality in trauma patients. Pro- and anti-inflammatory cytokines such as Il-6, Il-8 and Il-10 seem to play a superior role in the development of SIRS. Several studies support the hypothesis that the very early cytokine release pattern determines the patients' subsequent clinical course. Most data about interleukins in trauma patients however refer to serum concentrations assessed sometime in the first 24h, but there is only little information about release dynamics in a small-meshed time frame in the very initial post-trauma period. PATIENTS AND METHODS: 58 multiple injured patients (Injury Severity Score > 16 points) were included. Blood samples were drawn on patient admission (not later then 90 minutes after trauma) and at 6h, 12h, 24h, 48 h and 72 h. Il-6, Il-8 and Il-10 were measured using an automated chemiluminescence assay (IMMULITE, Siemens Healthcare Diagnostics GmbH). Interleukin levels were correlated to distinct epidemiological and clinical parameters. RESULTS: Interleukin serum concentrations are thoroughly elevated after trauma. Patients with haemorrhagic shock and consecutive massive RBC substitution (n = 27) exhibit higher Il-6, Il-8 and Il-10 levels as compared to patients with minor RBC transfusion extent (n = 31). Interleukin levels also differentiate patients with MOF (n = 43) from such without MOF (n = 15) already at the earliest post trauma time (90 minutes). Il-6, Il-8 and Il-10 concentrations also significantly distinguish patients with adverse outcome (n = 11) from such with favourable outcome (n = 47). Exclusively Il-10 has significant correlation to injury severity (ISS > 35). CONCLUSION: The current study presents an image of the serum Il-6, 8 and 10 releases in multiple trauma patients in the very early post-trauma period. We could thereby demonstrate that interleukin levels can clearly differentiate the presence of hemorrhagic shock and subsequent massive blood product substitution, the development of multiple organ failure and clinical outcome. No significant connection to age, gender and brain injury could be detected. Most importantly, changes in interleukin levels can be observed in the very early posttraumatic phase, at the earliest 90 minutes after trauma.

[The "time" factor. Its impact in pathophysiology and therapy of multiple trauma]. / Der Faktor "Zeit". Seine Bedeutung in der Pathophysiologie und Therapie des Polytraumas.

Pathophysiology of multiple trauma is characterized by different trauma-associated repercussions like organ destruction, haemorrhage, immune cell activation by foreign antigen, for example. The length of time while such impairments take hold of the organism substantially impacts the extent of the post trauma secondary injury. Short interruptions in microcirculation can mostly be compensated, whereas elongated ischemic periods definitely cause structural cell damage up to death. The current review highlights the importance of the time duration of posttrauma second hits on the pathophysiology of systemic inflammation and multiple organ failure. The quick termination of such secondary impairments by immediate therapeutic intervention mainly impacts the patients' prognosis.

Dynamics of neutrophilic NF-kB translocation in relation to IL-8 mRNA expression after major trauma.

OBJECTIVE: Systemic inflammation subsequent to polytrauma is connected to neutrophil (PMN) dysregulation characterized by reduced NF-kB-translocation and cytokine expression. The dynamics of NF-kB-activation as well as its down-stream regulation of IL-8-expression in PMN following major trauma remain unclear. The aim of this pilot study was to analyse NF-kB nuclear translocation in relation to IL- 8-mRNA-expression in PMN after major trauma. PATIENTS AND METHODS: PMN were isolated from blood samples of 15 major trauma patients (New Injury Severity Score, NISS > 16) drawn within 90 min and subsequently 6, 12, 24, 48, 72 h after trauma. NF-kB-translocation was analysed by Electrophoretic Mobility Shift Assay, EMSA and quantified by densitometry [arbitrary units], IL-8-mRNA-expression by RT-PCR, [copies/50 ng RNA]. Additionally, NF-kB-translocation and IL-8-expression in PMN of healthy volunteers were analysed natively (-control) and after LPS stimulation (+control). RESULTS: NF-kB-translocation and IL-8-mRNA-expression was significantly increased in polytrauma patients (n=15; NISS: 34 +/- 8 [mean +/- SEM]) initially. In non-survivors, NFkB- translocation was significantly increased on admission and subsequently reduced within 6 h, while it increased in the survivors group. After 24 h, a second significant increase in NF-kB-activity and IL-8-expression was found in survivors that was subsequently reduced in both groups. CONCLUSION: This pilot study has shown that a concomitant initial increase in transcriptional NF-kB-activity and IL-8 mRNA expression was observed in the early posttraumatic period which preceded the down-regulation of the innate immune system.

Cerebrospinal IL-10 concentration is elevated in non-survivors as compared to survivors after severe traumatic brain injury.

OBJECTIVE: The intrathecal posttraumatic inflammation contributes to secondary brain damage as well as to the induction of neuroreparative mechanisms. In this context release of interleukin-10 (IL-10) has been reported to play a major role. However, initial IL-10 concentration in CSF remains incompletely characterized. Therefore, the aim was to analyze Il-10 in CSF and serum of patients early after TBI. METHODS: For control, 10 volunteers receiving spinal puncture were enrolled. In patients with severe TBI (GCS<8 pts.), CSF and serum was drawn within 90+/-45 min after intraventricular catheter insertion (0 h), as well as 12 h, 24 h and 48 h after TBI. Albumin for assessing Blood-Brain-Barrier (BBB) function and IL-10 (IMMULITE, DPC Biermann, Bad Nauheim, Germany) were analyzed. RESULTS: 23 patients were enrolled. 15 survived and 8 deceased within 24h. In controls, CSF IL-10 was below detection limit (<5 pg/ml). In contrast, IL-10 was elevated significantly in non-survivors at 0 h vs. survivors and controls (30+/-6 vs. 9+/-1 vs. <5 pg/mL). This was accompanied by a significant increase of serum IL-10 in both groups at 0 h vs. controls (survivors: 30+/-6 pg/mL, non-survivors: 48+/-8 pg/mL, controls: 10+/-7 pg/mL, p<0.001). Survivors revealed signs of a mild BBB dysfunction during the entire observation period. In contrast, non-survivors presented a severe BBB breakage. CONCLUSIONS: We demonstrated an analysis of IL-10 CSF and serum concentration after TBI. These data support an intrathecal IL-10 synthesis. Although the significant increase of IL-10 might indicate a bad outcome of TBI, responsible mechanisms still have to be elucidated.

Gene expression profiles are influenced by ISS, MOF, and clinical outcome in multiple injured patients: a genome-wide comparative analysis.

BACKGROUND: Posttraumatic immune system activation in major trauma patients is linked to systemic inflammatory response syndrome, multiple organ failure (MOF), and mortality. Recent studies suggest that genome-wide expression is altered in response to distinct clinical parameters; however, the functional allocation of theses genes remains unclear. PATIENTS AND METHODS: Thirteen patients after major trauma (Injury Severity Score < 16) were studied. Monocytes were obtained on admission (within 90 min) and at 6, 12, 24, 48, and 72 h after trauma. Complementary ribonucleic acid (RNA) targets were hybridized to Affymetrix HG U 133A microarrays. Searching for genes that are differentially expressed, the patients were dichotomously assigned depending upon survival, injury severity, and MOF. The data were analyzed by supervised analysis, clustering, and comparative pathway analysis. RESULTS: Gene expression profiles of patients with adverse outcomes (763 probe sets) mainly consist of those involved in "immunological activation" or "cellular movement," whereas the gene set associated with MOF (660) is associated with "cancer" and "cell death." Injury severity (295) leads to an overexpression of genes involved in inflammatory disease. CONCLUSION: We demonstrate for the first time a serial, sequential screening analysis of monocyte messenger RNA expression patterns after multiple injury indicating a strongly significant connection between the patients' expression profile and different clinical parameters. The latter provoke a characteristic overexpression of specific functional gene ontologies. Further studies to clarify clinical consequence of this differential gene regulation are currently anticipated.