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.

The sequential trauma score - a new instrument for the sequential mortality prediction in major trauma.

BACKGROUND: There are several well established scores for the assessment of the prognosis of major trauma patients that all have in common that they can be calculated at the earliest during intensive care unit stay. We intended to develop a sequential trauma score (STS) that allows prognosis at several early stages based on the information that is available at a particular time. STUDY DESIGN: In a retrospective, multicenter study using data derived from the Trauma Registry of the German Trauma Society (2002-2006), we identified the most relevant prognostic factors from the patients basic data (P), prehospital phase (A), early (B1), and late (B2) trauma room phase. Univariate and logistic regression models as well as score quality criteria and the explanatory power have been calculated. RESULTS: A total of 2,354 patients with complete data were identified. From the patients basic data (P), logistic regression showed that age was a significant predictor of survival (AUC(model P), area under the curve = 0.63). Logistic regression of the prehospital data (A) showed that blood pressure, pulse rate, Glasgow coma scale (GCS), and anisocoria were significant predictors (AUC(model A) = 0.76; AU(model P + A) = 0.82). Logistic regression of the early trauma room phase (B1) showed that peripheral oxygen saturation, GCS, anisocoria, base excess, and thromboplastin time to be significant predictors of survival (AUC(model B1) = 0.78; AUC(model P + A + B1) = 0.85). Multivariate analysis of the late trauma room phase (B2) detected cardiac massage, abbreviated injury score (AIS) of the head > or = 3, the maximum AIS, the need for transfusion or massive blood transfusion, to be the most important predictors (AUC(model B2) = 0.84; AUC(final model P + A + B1 + B2) = 0.90). The explanatory power - a tool for the assessment of the relative impact of each segment to mortality - is 25% for P, 7% for A, 17% for B1 and 51% for B2. A spreadsheet for the easy calculation of the sequential trauma score is available at: www.sequential-trauma-score.com CONCLUSIONS: This score is the first sequential, dynamic score to provide a prognosis for patients with blunt major trauma at several points in time. With every additional piece of information the precision increases. The medical team has a simple, useful tool to identify patients at high risk and to predict the prognosis of an individual patient with major trauma very early, quickly and precisely.

[Analysis of failure modes in multislice computed tomography during primary trauma survey]. / Analyse von Verzögerungen der Schockraumdiagnostik bei Einsatz der Mehrschicht-Spiral-Computertomografie.

PURPOSE: In the case of major trauma, immediate recognition and treatment of life-threatening conditions are essential. An increasing number of European trauma centers use MSCT during the primary trauma survey due to its high diagnostic precision and speed. However, there is currently little empirical data about failures in this process to practice quality assurance. The aim of this study was to evaluate this process under operating resuscitation conditions and to identify failure modes that caused delays in completion. MATERIALS AND METHODS: An independent study monitor documented the course of trauma room treatment during a 10-month period. The inclusion criteria were patients who were admitted directly from the accident scene and the study monitor was present at the time of admission. RESULTS: According to our ATLS-based trauma algorithm whole-body CT (WBCT) consists of non-contrast head CT (CCT) and contrast-enhanced trunk CT (TCT). 57 trauma patients receiving 45 WBCT. 5 single CCT and 4 single TCT studies were evaluated. After initial resuscitation, CCT was obtained within 17 min of trauma room admission (IQR 13.0 - 20.0). In 20 % (95 %CI 9 - 31 %) of the cases, a CCT delay of median 5.0 min (IQR 3.8 - 8.0) was observed caused by e. g. earings, piercings and ECG cables in the scan field or intoxicated patients. Contrast-enhanced TCT was performed after 23.0 min (IQR 19.0 - 27.0). Due to preventable errors 12 of the 49 TCT studies were delayed (25 % 95 %CI 12 - 37 %) for 5 min (IQR 3.0 - 8.0). CONCLUSION: Under "front line" conditions every fifth CCT and every fourth TCT study was completed with a median delay of 5 min. An independent process analysis revealed that unpreventable delays were due to uncooperative patients or system failure. Preventable delays were due to errors such as short intravenous lines or deviation from trauma room algorithms. Preventable delays could be avoided by addressing human and technical aspects such as revising checklists and functional architecture of the trauma bay. The failure mode and effect analysis (FMEA) method would assure quality in this process.

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.

Snapshot assessment of RNA-expression in severely burned patients using the PAXgene Blood RNA system: a pilot study.

Severe burn induces destabilization of the immune system and the likelihood of multiple organ dysfunction syndrome. Current studies focus on RNA-expression analyses of immune system cells, however, the present methods of analysis are complex, potentially altered by artefacts and therefore not feasible for routine analyses. The new PAXgene Blood RNA System provides "snapshot" analysis of RNA by immediate cell lysis and prevention of RNA-degradation. Using this system the aim of this study was to analyse intracellular cytokine RNA-expression under clinical conditions. Whole blood samples (PAXgene tubes) of nine severely burned patients were drawn at admission and 6, 12, 24, 48 and 72h after trauma during routine treatment. Four healthy individuals served as control. Analysis of RNA-expression of TNF-alpha as pro-inflammatory and IL-10 as anti-inflammatory mediator was performed by RT-PCR. The RNA-expression of TNF-alpha was increased at 72h after burn. The increase occurred mainly in surviving patients. In contrast, RNA-expression of IL-10 was elevated already at 24h and the difference between surviving and deceased patients occurred earlier. We demonstrate for the first time a "snapshot" analysis of cytokine RNA-expression in severely burned patients under routine conditions. The results correspond well to current hypothesis of posttraumatic MODS development.

[Diagnosis and treatment of paronychia]. / Wann schienen, wann schneiden?

Paronychia is a purulent infection of the lateral fingertip, and represents the most common infectious disease affecting the hand.The typical germ is Staphylococcus aureus, while a mixture of bacteria or pathogens of a different kind are usually seen in patients with immunodeficiency. Treatment ranges from bathing the finger in an antiseptic solution to lancing the abscess.

Persistent pulmonary consolidation treated with intrapulmonary percussive ventilation: a preliminary report.

Intrapulmonary percussive ventilation (IPV) is a novel form of chest physiotherapy delivered by a percussive pneumatic device (IPV, Percussionaire, Sand Point, ID). There are few published reports about the use of IPV for diseases other than cystic fibrosis. We report our experience with three pediatric patients and one adult patient with persistent pulmonary consolidation refractory to conventional therapies. Three of the four patients had neuromuscular disease; one patient had segmental atelectasis due to aspiration. Three of the four patients showed clinical and radiographic improvement within 48 hours of starting IPV. The fourth patient experienced brief episodes of third-degree atrioventricular block, hypoxemia, and bradycardia during two IPV treatments. IPV was safely restarted and he slowly improved. We conclude that while IPV requires further clinical evaluation, it appears to be a safe and effective therapy for selected patients. However, close observation is essential during and after IPV treatments, especially in patients who have difficulty mobilizing or expectorating sputum.

Duration and predictors of emergency surgical operations--basis for medical management of mass casualty incidents.

BACKGROUND: Hospitals have a critically important role in the management of mass causality incidents (MCI), yet there is little information to assist emergency planners. A significantly limiting factor of a hospital's capability to treat those affected is its surgical capacity. We therefore intended to provide data about the duration and predictors of life saving operations. METHODS: The data of 20,815 predominantly blunt trauma patients recorded in the Trauma Registry of the German-Trauma-Society was retrospectively analyzed to calculate the duration of life-saving operations as well as their predictors. Inclusion criteria were an ISS≥16 and the performance of relevant ICPM-coded procedures within 6h of admission. RESULTS: From 1,228 patients fulfilling the inclusion criteria 1,793 operations could be identified as life-saving operations. Acute injuries to the abdomen accounted for 54.1% followed by head injuries (26.3%), pelvic injuries (11.5%), thoracic injuries (5.0%) and major amputations (3.1%). The mean cut to suture time was 130min (IQR 65-165min). Logistic regression revealed 8 variables associated with an emergency operation: AIS of abdomen ≥3 (OR 4,00), ISS ≥35 (OR 2,94), hemoglobin level ≤8 mg/dL (OR 1,40), pulse rate on hospital admission <40 or >120/min (OR 1,39), blood pressure on hospital admission <90 mmHg (OR 1,35), prehospital infusion volume ≥2000 ml (OR 1,34), GCS ≤8 (OR 1,32) and anisocoria (OR 1,28) on-scene. CONCLUSIONS: The mean operation time of 130min calculated for emergency life-saving surgical operations provides a realistic guideline for the prospective treatment capacity which can be estimated and projected into an actual incident admission capacity. Knowledge of predictive factors for life-saving emergency operations helps to identify those patients that need most urgent operative treatment in case of blunt MCI.

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.

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.

[Tension pneumopericardium--a rare complication in multiply injured patients]. / Spannungspneumoperikard als seltene Komplikation bei schwerem Polytrauma.

Thoracic injury is a relevant and common complication in multiply injured patients. Typical patterns of injury comprise rib fractures, serious lung trauma as well as diaphragmatic and aortic rupture. In contrast, posttraumatic tension pneumopericardium following blunt thoracic trauma is a very rare complication. However, if unrecognized it might provoke cardiac tamponade and death. For the development of a pneumopericardium, free air follows the vessel bundles up to the pericardium. Hence, if the number of ruptured alveoli is high, or these alveoli are placed close to the heart, and if additional risk factors, such as high inspiratory ventilation pressure, are present, a tension pneumopericardium can induce cardiac tamponade. The aim of this report is to illuminate diagnostic and therapeutic strategies for posttraumatic pneumopericardium by presentation of a case from our trauma centre and a critical discussion of the present literature.

[The presence of family members in the trauma room]. / Die Präsenz von Angehörigen im Schockraum.

The fate of multiple trauma patients is witnessed by a considerable number of relatives. Although numerous studies report that the patient's course and treatment success are dependent on the family's confidence as well as its clarification over the clinical situation, scientifically based guidelines for contact with relatives in the context of acute care following severe traumatic injuries do not yet exist. The current guidelines of the European Resuscitation Council recommend the concept of "on scene" presence for the integration of the relatives into acute care in situations of circulatory and heart failure, thus recommending the presence of relatives during acute medical care. This article discusses this concept and argues for a possible assignment of management of trauma care for severe and gravely injured patients.

A versatile simulator of evoked potentials.

A simple electronic device is described which simulates evoked potentials with variable amounts of superimposed noise to facilitate routine checking and testing of apparatus and computer programs in an evoked potential laboratory.