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Lumbopelvic distraction stabilization with (triangular osteosynthesis) or without additional iliosacral screw allows anatomic reduction of the posterior pelvic ring after severely displaced sacral fractures, correction or resection osteotomies of malunions, respectively, septic sacroiliitis and permits early weight bearing. However, this technique is complicated by wound necrosis or infection in up to 20% to 30%. We describe our experience with a less invasive technique.The presented technique was performed in a consecutive series (December 2006 to October 2009) of 10 patients (mean age: 47 years, 23-85 years; 5 men). Posterior pelvic ring instability was due to severely displaced vertical shear injuries of type C1/3.3 (6/10), delayed union 2 months after bilateral C 3.3 (1/10) fractures, and malunion 6 months after unilateral vertical shear injuries C 1.3 (1/10), occurred after resection of the iliosacral joint for treatment of spinal tuberculosis (1/10) or was related to a early loss of reduction of a type C 1.3 pelvic ring injury (1/10). Patients were prospectively evaluated for the occurrence of wound-healing disorders with a median follow-up of 9 months (range, 5-33).The median duration of the hospital stay was 35 days (range, 16-57). One 85-year-old patient died 1 year after lumbopelvic stabilization for reasons unrelated to the surgical treatment. In the postoperative course, no wound-healing disorders or infections were observed, and in all cases, the soft tissues and the bone healed. Five of 10 removal of the lumbopelvic fixation was performed at a median of 8 months (range, 8-20) after stabilization to prevent sacroiliac arthrodesis or to mobilize the lumbar spine after the unilateral lumbopelvic stabilization. The indication for hardware removal was not related to wound disorders.The presented technique respects the lumbar anatomy and provides the access required for lumbopelvic stabilization, while having the potential to decrease or even prevent postoperative wound disorders if combined with a polyaxial low-profile system. The low number of cases presented may, however, limit the relevance of the conclusions in cases of severe Morell-Lavallé lesions with skin disorders.

This study evaluated critical thresholds for fresh frozen plasma (FFP) and platelet (PLT) to packed red blood cell (PRBC) ratios and determined the impact of high FFP:PRBC and PLT:PRBC ratios on outcomes in patients requiring massive transfusion (MT).Retrospective review of a cohort of massively transfused blunt trauma patients admitted to a Level I trauma center. MT was defined as transfusion of ≥10 units of PRBC within 24 hours of admission. Critical thresholds for FFP:PRBC and PLT:PRBC ratios associated with mortality were identified using Cox regression with time-dependent variables. Impacts of high blood component ratios on 12-hour and 24-hour survival were evaluated.During the 10-year study period, a total of 229 blunt trauma patients required a MT. At 12 hours and 24 hours after admission, a FFP:PRBC ratio threshold of 1:1.5 was found to have the strongest association with mortality. At 12 hours, 58 patients (25.4%) received a low (1:1.5) and 171 patients (74.6%) a high (≥1:1.5) FFP:PRBC ratio. Patients in the low ratio group had a significantly higher mortality compared with those in the high ratio group (51.7% vs. 9.4%; adjusted hazard ratio [95% confidence interval] = 1.18 [1.04-1.34]; adjusted p = 0.008). A similar statistically significant difference was found at 24 hours after admission. For PLTs, a PLT:PRBC ratio of 1:3 was identified as the best cut-off associated with both 12-hour and 24-hour survival. At 12 hours, 79 patients (34.5%) received a low (1:3) and 150 patients (65.5%) a high (≥1:3) PLT:PRBC ratio. After adjusting for differences between the ratio groups, no statistically significant survival advantage associated with a high PLT:PRBC ratio was found (40.5% vs. 9.3%; adjusted hazard ratio [95% confidence interval] = 1.11 [0.99-1.26]; adjusted p = 0.082).For massively transfused blunt trauma patients, a plasma to PRBC ratio of ≥1:1.5 was associated with improved survival at 12 hours and 24 hours after hospital admission. However, for PLTs, no statistically significant survival benefit with increasing ratio was observed. The results of this analysis highlight the need for prospective studies to evaluate the clinical significance of high blood component ratios on outcome.

Background: This study aims to quantify by intravital microscopy the microhemodynamic response after extracorporeal shock wave application (ESWA) to the physiologic microcirculation of the mouse dorsal skinfold chamber. Materials and Methods: ESWA was carried out using an electrohydraulic shock wave source. Two different shock wave doses of 500 and 1000 pulses at an energy flux rate of 0.08 mJ/mm2 and a frequency of 4 Hz were compared with sham-operated animals. Microcirculatory analyses were performed at baseline (BL) and during a 3 d observation period after ESWA. The expression of caspase-3 (casp-3), proliferating cell nuclear antibody (PCNA), von Willebrand factor (vWF), and endothelial nitric oxide synthase (eNOS) were analyzed semiquantitatively by immunohistochemistry. Results: ESWA provoked a significant and persistent increase of functional capillary density (FCD) throughout the observation period, reaching a maximum (140% ± 5% of BL, P < 0.05 versus sham) after 1 d when animals were treated with 1000 pulses. ESWA induced a slight increase of leukocyte rolling (not, vert, similar2- to not, vert, similar3.5-fold, P < 0.05) and leukocyte adherence (not, vert, similar1.5- to not, vert, similar2-fold, P < 0.05) to the endothelial lining of postcapillary venules. One day following ESWA, we observed enhanced expression of casp-3 (not, vert, similar3- to not, vert, similar4-fold), PCNA (not, vert, similar9- to not, vert, similar14-fold), vWF (not, vert, similar11- to not, vert, similar14-fold), and eNOS (not, vert, similar3-fold), all P < 0.05. Conclusion: This study shows that ESWA provokes a favorable persistent increase of patent capillaries, however accompanied by a transient and slight inflammatory response but also by dose-dependant apoptotic cell death. Our data suggest that ESWA might represent a noninvasive biomechanical tool to treat critically perfused and endangered tissues, but certainly warrants further investigation.

Background: To prevent iatrogenic damage, transfusions of red blood cells should be avoided. For this, specific and reliable transfusion triggers must be defined. To date, the optimal hematocrit during the initial operating room (OR) phase is still unclear in patients with severe traumatic brain injury (TBI). We hypothesized that hematocrit values exceeding 28%, the local hematocrit target reached by the end of the initial OR phase, resulted in more complications, increased mortality, and impaired recovery compared to patients in whom hematocrit levels did not exceed 28%. Methods: Impact of hematocrit (independent variable) reached by the end of the OR phase on mortality and morbidity determined by the extended Glasgow outcome scale (eGOS; dependent variables) was investigated retrospectively in 139 TBI patients. In addition, multiple logistic regression analysis was performed to identify additional important variables. Findings: Following severe TBI, mortality and morbidity were neither aggravated by hematocrit above 28% reached by the end of the OR phase nor worsened by the required transfusions. Upon multiple logistic regression analysis, eGOS was significantly influenced by the highest intracranial pressure and the lowest cerebral perfusion pressure values during the initial OR phase. Conclusions: Based on this retrospective observational analysis, increasing hematocrit above 28% during the initial OR phase following severe TBI was not associated with improved or worsened outcome. This questions the need for aggressive transfusion management. Prospective analysis is required to determine the lowest acceptable hematocrit value during the OR phase which neither increases mortality nor impairs recovery. For this, a larger caseload and early monitoring of cerebral metabolism and oxygenation are indispensable

Background: Trauma patients are at high risk of developing systemic inflammatory response syndrome (SIRS) and infections. The aim of this study was to evaluate the influence of the severity of injury and the extent of hemorrhagic shock at admission on the incidence of SIRS, infection and septic complications. Methods: A total of 972 patients who had an injury severity score (ISS) of ‡ 17, survived more than 72 h, and were admitted to a level I trauma center within 24 h after trauma were included in this retrospective analysis. SIRS, sepsis and infection rates were measured in patientswith different severities of injury as assessed by ISS, or with various degrees of hemorrhagic shock according to ATLS� guidelines, andwere compared using both uni- and multivariate analysis. Results: Infection rates and septic complications increase significantly (p < 0.001) with higher ISS. Severe hemorrhagic shock on admission is associated with a higher rate of infection (72.8%) and septic complications (43.2%) compared to mild hemorrhagic shock (43.4%, p < 0.001 and 21.7%, p < 0.001, respectively). Conclusions: The severity of injury and the severity of hemorrhagic shock are risk factors for infectious and septic complications. Early diagnostic and adequate therapeutic work up with planned early ‘‘second look’’ interventions in such high-risk patients may help to reduce these common posttraumatic complications.

OBJECTIVES: The level of pancreatic stone protein/regenerating protein (PSP/reg), a secretory protein produced in the pancreas, increases dramatically during pancreatic disease. However, after stress (e.g., anesthesia), PSP/reg levels are increased transiently in animals without pancreatic injury. Therefore, we aimed to determine whether PSP/reg is an acute-phase protein after nonpancreatic trauma. PATIENTS: Eighty-three polytraumatic patients without pancreatic damage. MEASUREMENTS AND MAIN RESULTS: We compared serum PSP/reg levels from polytraumatic patients without pancreatic damage with those in healthy controls (n = 38). C-reactive protein, interleukin-6, procalcitonin, and leukocyte numbers were also compared. The expression of CD62L and CD11b on neutrophils after exposure to PSP/reg was analyzed by flow cytometry. Thirty-three patients (39%) developed sepsis, 32 (38%) had local infections, and 18 (21%) had no infections. At admission, PSP/reg serum levels (10.2 [6.2-14.5] ng/mL; median [interquartile range]) were comparable with those in healthy controls (10.4 [7.5-12.3] ng/mL). During hospital stay, PSP/reg levels were elevated significantly in patients with sepsis (146.4 ng/mL) and in patients with infections (111.4 ng/mL) compared with patients without infections (22.8 ng/mL). Furthermore, binding of fluorescein isothiocyanate-labeled recombinant PSP/reg to human neutrophils was demonstrated. Recombinant PSP/reg elicited a dose-dependent shedding of L-selectin (CD62L) and upregulation of beta2-integrin (CD11b) in neutrophils, which indicates that PSP/reg activates neutrophils. CONCLUSIONS: We conclude that PSP/reg is up-regulated in blood after trauma, and the PSP/reg level is related to the severity of inflammation. Furthermore, PSP/reg binds to and activates neutrophils. Therefore, PSP/reg might be an acute-phase protein that could serve as a marker for posttraumatic complications.

BACKGROUND: Clinical observations are suggesting accelerated granulation tissue formation in traumatic wounds treated with vacuum-assisted closure (VAC). Aim of this study was to determine the impact of VAC therapy versus alternative Epigard application on local inflammation and neovascularization in traumatic soft tissue wounds. METHODS: Thirty-two patients with traumatic wounds requiring temporary coverage (VAC n = 16; Epigard n = 16) were included. At each change of dressing, samples of wound fluid and serum were collected (n = 80). The cytokines interleukin (IL)-6, IL-8, vascular endothelial growth factor (VEGF), and fibroblast growth factor-2 were measured by ELISA. Wound biopsies were examined histologically for inflammatory cells and degree of neovascularization present. RESULTS: All cytokines were found to be elevated in wound fluids during both VAC and Epigard treatment, whereas serum concentrations were negligible or not detectable. In wound fluids, significantly higher IL-8 (p < 0.001) and VEGF (p < 0.05) levels were detected during VAC therapy. Furthermore, histologic examination revealed increased neovascularization (p < 0.05) illustrated by CD31 and von Willebrand factor immunohistochemistry in wound biopsies of VAC treatment. In addition, there was an accumulation of neutrophils as well as an augmented expression of VEGF (p < 0.005) in VAC wound biopsies. CONCLUSION: This study suggests that VAC therapy of traumatic wounds leads to increased local IL-8 and VEGF concentrations, which may trigger accumulation of neutrophils and angiogenesis and thus, accelerate neovascularization.

The management of severe open fractures of the lower leg continues to challenge the treating surgeon. Major difficulties include high infection rates as well as adequate temporary soft tissue coverage. In the past, these injuries were commonly associated with loss of the extremity. Today, vacuum therapy provides not only safe temporary wound coverage but also conditioning of the soft tissues until definitive wound closure. Amongst other advantages, bacterial clearance and increased formation of granulation tissue are attributed to vacuum therapy, making it an extremely attractive tool in the field of wound healing. However, despite its clinical significance, which is underlined by a constantly increasing range of indications, there is a substantial lack of basic research and well-designed studies documenting the superiority of vacuum therapy compared to alternative wound dressings. Vacuum therapy has been approved as an adjunct in the treatment of severe open fractures of the lower leg, complementing repeated surgical debridement and soft tissue coverage by microvascular flaps, which are still crucial in the treatment of these limb-threatening injuries. Vacuum therapy has in general proven useful in the management of soft tissue injuries and, since it is generally well tolerated and has low complication rates, it is fast becoming the gold standard for temporary wound coverage in the treatment of severe open fractures of the lower leg

BACKGROUND: Elevated lactate and interleukin-6 (IL-6) levels were shown to correlate with mortality and multiple organ dysfunction in severely traumatized patients. The purpose of this study was to test whether an association exists between 24-hour lactate clearance, IL-6 and procalcitonin (PCT) levels, and the development of infectious complications in trauma patients. METHODS: A total of 1757 consecutive trauma patients with an Injury Severity Score (ISS) > 16 admitted over a 10-year period were retrospectively analyzed over a 21-day period. Exclusion criteria included death within 72 h of admission (24.5%), late admission > 12 h after injury (16%), and age < 16 years (0.5%). Data are stated as the median (range). RESULTS: Altogether, 1032 trauma patients (76.2% male) with an average age of 38 years, a median ISS of 29 (16-75), and an Acute Physiology, Age, and Chronic Health Evaluation (APACHE) II score of 14 (0-40) were evaluated. The in-hospital mortality (>3 days) was 10%. Patients with insufficient 24-hour lactate clearance had a high rate of overall mortality and infections. Elevated early serum procalcitonin on days 1 to 5 after trauma was strongly associated with the subsequent development of sepsis (p < 0.01) but not with nonseptic infections. The kinetics of IL-6 were similar to those of PCT but did differentiate between infected and noninfected patients after day 5. CONCLUSIONS: This study demonstrates that elevated early procalcitonin and IL-6 levels and inadequate 24-hour lactate clearance help identify trauma patients who develop septic and nonseptic infectious complications. Definition of specific cutoff values and early monitoring of these parameters may help direct early surgical and antibiotic therapy and reduce infectious mortality.

BACKGROUND: The noble gas helium is devoid of anesthetic effects, and it elicits cardiac preconditioning. We hypothesized that inhalation of helium provides protection against postocclusive endothelial dysfunction after ischemia-reperfusion of the forearm in humans. METHODS: Eight healthy male subjects were enrolled in this study with a crossover design. Each volunteer was randomly exposed to 15 min of forearm ischemia in the presence or absence of helium inhalation. Helium was inhaled at an end-tidal concentration of 50 vol% from 15 min before ischemia until 5 min after the onset of reperfusion ("helium conditioning"). Hyperemic reaction, a marker of nitric oxide bioavailability and endothelial function, was determined at 15 and 30 min of reperfusion on the forearm using venous occlusion plethysmography. Expression of the proinflammatory markers CD11b, ICAM-1, PSGL-1, and L-selectin (CD62L) on leukocytes and P-selectin (CD62P), PSGL-1, and CD42b on platelets were measured by flow cytometry during reperfusion. RESULTS: Ischemia-reperfusion consistently reduced the postocclusive endothelium-dependent hyperemic reaction at 15 and 30 min of reperfusion. Periischemic inhalation of helium at 50 vol% did not improve postocclusive hyperemic reaction. Helium decreased expression of the proinflammatory marker CD11b and ICAM-1 on leukocytes and attenuated the expression of the procoagulant markers CD42b and PSGL-1 on platelets. CONCLUSIONS: Although inhalation of helium diminished the postischemic inflammatory reaction, our data indicate that human endothelium, which is a component of all vital organs, is not amenable to protection by helium at 50 vol% in vivo. This is in contrast to sevoflurane, which protects human endothelium at low subanesthetic concentrations.

Background: : Unstable pelvic ring fractures with exsanguinating hemorrhages are rare but potentially lifethreatening injuries. The aim of this retrospective study was to evaluate whether early changes in acid- base parameters predict mortality of patients with severe pelvic trauma and hemorrhagic shock. Methods: : Data for 50 patients with pelvic ring disruption and severe hemorrhage were analyzed retrospectively. In all patients, the pelvic ring was temporarily stabilized by C-clamp. Patients with ongoing bleeding underwent laparotomy with extra and/or intraperitoneal pelvic packing, as required. Base excess, lactate, and pH were measured upon admission and at 1, 2, 3, 4, 6, 8, and 12 h postadmission. Patients were categorized as early survivors (surviving the first 12 h after admission) and nonsurvivors. Statistical analysis was performed by Mann-Whitney test; significance was assumed at p < 0.05. Receiver operating characteristic curves were generated for early mortality from each acid-base variable. Results: : Sixteen patients (32%) were nonsurvivors due to hemorrhagic shock (n = 13) or severe traumatic brain injury (n = 3). Thirty-four patients were early survivors. Base excess, lactate, and pH significantly discriminated between early survivors and nonsurvivors. Base excess determined 1 h after admission discriminated most strongly, with an area under the receiver operating characteristic curve of 0.915 (95% confidence interval, 0.836-0.993; p < 0.001). Conclusion: : Base excess, lactate, and pH discriminate early survivors from nonsurvivors suffering from severe pelvic trauma and hemorrhagic shock. Base excess measured 1 h after admission best predicted early mortality following pelvic trauma with concomitant hemorrhage

Background To investigate whether the compartment pressure of the rectus sheath (CPRS) reflects the intra-abdominal pressure (IAP) under various conditions of intra-abdominal hypertension (IAH) in a pig model. Methods Design: Prospective experimental study with in vivo pressure measurements. Setting: Institute for Clinical and Experimental Surgery, University of Saarland. Animals: Seven domestic male pigs (body weight 34.8 ± 2.5kg). Interventions: Stepwise increase and decrease of IAP by means of CO2 pneumoperitoneum. Continuous direct measurement of the IAP and correspondent indirect IAP measurement techniques including analysis of intravesical pressure (IVP), femoral vein pressure (FVP), and CPRS. Results Bland-Altman analysis comparing direct IAP measurement with correspondent CPRS showed good agreement for IAP between 12mm Hg and 30mm Hg (bias −0.5mm Hg, lower and upper limits of agreement (LLA/ULA) −3.5/2.5mm Hg). FVP (bias −0.3mm Hg, LLA/ULA −2.3/1.6mm Hg) and IVP (bias 0.4mm Hg, LLA/ULA −2.1/2.9mm Hg) demonstrated similar results compared with direct IAP measurement. Agreement was worse for all indirect IAP measurement techniques for IAP Conclusions CPRS accurately reflects IAP for IAP ≥ 12mm Hg. Accuracy is similar to established indirect IAP measurement techniques.

Background and Purpose:: Heterotopic ossification (HO) often follows acetabular fractures after multitrauma. Irradiation is a mean for prophylaxis. We established a standard procedure in our hospital for patients under sedation, when obtaining informed consent for HO prophylaxis is impossible. Patients and Methods:: We reviewed current scientific evidence, calculated the risks of radiation and presented the ethical and legal framework. The subject was scrutinised by an interdisciplinary panel. Results:: Irradiation is the most effective means for prophylaxis and has few adverse effects in adult patients with fractures of the acetabulum. The lifetime risk of radiation-induced cancer or infertility are insignificant. Conclusions:: Informed consent for irradiation should be obtained before operation whenever possible. When this cannot be done prophylaxis can be postponed for a maximum of 3 days in order to obtain consent. If the patient is not able to communicate within this period, prophylactic irradiation should be given after consulting the relatives. The patient must be informed as soon as possible

Introduction Norepinephrine, regularly used to increase systemic arterial blood pressure and thus improve cerebral perfusion following severe traumatic brain injury (TBI), may activate platelets. This, in turn, could promote microthrombosis formation and induce additional brain damage. Methods The objective of this study was to investigate the influence of norepinephrine on platelets isolated from healthy volunteers and TBI patients during the first two post-traumatic weeks. A total of 18 female and 18 male healthy volunteers of different age groups were recruited, while 11 critically ill TBI patients admitted consecutively to our intensive care unit were studied. Arterial and jugular venous platelets were isolated from norepinephrine-receiving TBI patients; peripheral venous platelets were studied in healthy volunteers. Concentration-dependent functional alterations of isolated platelets were analyzed by flow cytometry, assessing changes in surface P-selectin expression and platelet-derived microparticles before and after in vitro stimulation with norepinephrine ranging from 10 nM to 100 μM. The thrombin receptor-activating peptide (TRAP) served as a positive control. Results During the first week following TBI, norepinephrine-mediated stimulation of isolated platelets was significantly reduced compared with volunteers (control). In the second week, the number of P-selectin- and microparticle-positive platelets was significantly decreased by 60% compared with the first week and compared with volunteers. This, however, was associated with a significantly increased susceptibility to norepinephrine-mediated stimulation, exceeding changes observed in volunteers and TBI patients during the first week. This pronounced norepinephrine-induced responsiveness coincided with increased arterio-jugular venous difference in platelets, reflecting intracerebral adherence and signs of cerebral deterioration reflected by elevated intracranial pressure and reduced jugular venous oxygen saturation. Conclusion Clinically infused norepinephrine might influence platelets, possibly promoting microthrombosis formation. In vitro stimulation revealed a concentration- and time-dependent differential level of norepinephrine-mediated platelet activation, possibly reflecting changes in receptor expression and function. Whether norepinephrine should be avoided in the second post-traumatic week and whether norepinephrine-stimulated platelets might induce additional brain damage warrant further investigations.

Background Endothelial cells can be protected against cytokine-induced toxicity by volatile anesthetics. The authors tested whether inhalation of sevoflurane at subanesthetic concentrations provides protection against postocclusive endothelial dysfunction induced by ischemia-reperfusion injury of the forearm in humans. Methods Five healthy male volunteers were enrolled in this study with crossover design. Each subject was randomly exposed to 15 min of forearm ischemia in the presence or absence of sevoflurane. Sevoflurane was inhaled at 0.5-1 vol% end-tidal concentrations from 15 min before ischemia until 5 min after the onset of reperfusion. Hyperemic reaction, an indicator of ischemic injury and endothelial function, was determined at 15 and 30 min of reperfusion using venous occlusion plethysmography. Also, markers of leukocyte activation (CD11b, CD42b) were measured by flow cytometry during reperfusion. Results Fifteen minutes of forearm ischemia followed by reperfusion diminished postocclusive endothelium-dependent hyperemic reaction at 15 and 30 min of reperfusion. Peri-ischemic inhalation of sevoflurane, targeted at 0.5-1 vol% end-tidal concentrations, markedly improved postocclusive hyperemic reaction. In addition, inhalation of sevoflurane attenuated activation of leukocytes, as measured by CD11b expression, after ischemia-reperfusion injury. No changes in CD42b expression were observed after ischemia-reperfusion of the forearm. Conclusions These data suggest that human endothelium, a key component of all vital organs, is receptive to protection by sevoflurane in vivo. Peri-ischemic administration of sevoflurane mimics a combination of pharmacologic preconditioning and postconditioning and protects at even low sedative concentrations (< 1 vol%). Inhibition of leukocyte adhesion is likely to be involved in the protection.

The use of the vascularized iliac crest to reconstruct bone defect has been published in 1979 but has gained very little popularity in the fields of the reconstructive surgery of the extremities. The usual approach to harvest vascularized iliac crest goes through the inguinal ligament. Up to 10% of inguinal hernia and above 20% of sensory loss have been reported as complication with this approach. On the other hand, the iliac crest offers larger amount of rapidly integrated cancellous bone as compared to vascularized fibula. The pararectus approach has been initially used for internal fixation of acetabular fractures. This approach gives direct access to the branches of the external iliac artery without interruption of the inguinal ligament. In this anatomical study, 5 human specimens preserved with the Thiel-Method and injected with colored latex were harvested on both side with the pararectus approach. The goal of the study was to assess if this approach gives easily access to the deep circumflex iliac artery (DCIA) vascularizing the anterior iliac crest. The approach consisted into an incision of the rectus sheath at the lateral border of the rectus abdominis and then to a retrograde dissection the deep inferior epigastric vessels up to the external iliac artery and veins in the retroperitoneal space. In all specimens, the level of the origin of the deep circumflex iliac vessels coincided with the origin of the deep inferior epigastric vessels on the external and internal border of the external iliac vessels, respectively. To harvest large scale vascularized iliac crest the pararectus approach was extended to the supraumbilical level with incision of the anterior and posterior sheath of the rectus abdominis. With this approach, the maximum size of harvested bone was 8 × 5 cm, preserving the first 2 cm of the anterosuperior iliac spine. In all harvested sides, the anterograde dissection of the lateral femoral cutaneous nerve and of the genitofemoral nerve was easy and allowed a safe harvest of the deep cicumflex iliac vessels. In conclusion, the pararectus approach extended to the supraumbilical space give an easy access to the deep circumflex iliac vessels and very large size of vascularized iliac crest. This approach respects the inguinal ligament and is easy to close. We are now using this approach in a preliminary clinical study to harvest vascularized iliac crest of large scale.

Systemic factors are believed to be pivotal for the development of heterotopic ossification in severely-injured patients. In this study, cell cultures of putative target cells (human fibroblastic cells, osteoblastic cells (MG-63), and bone-marrow stromal cells (hBM)) were incubated with serum from ten consecutive polytraumatised patients taken from post-traumatic day 1 to day 21 and with serum from 12 healthy control subjects. The serum from the polytraumatised patients significantly stimulated the proliferation of fibroblasts, MG-63 and of hBM cells. The activity of alkaline phosphatase in MG-63 and hBM cells was significantly decreased when exposed to the serum of the severely-injured patient. After three weeks in 3D cell cultures, matrix production and osteogenic gene expression of hBM cells were equal in the patient and control groups. However, the serum from the polytraumatised patients significantly decreased apoptosis of hBM cells compared with the control serum (4.3% vs 19.1%, p = 0.031). Increased proliferation of osteoblastic cells and reduced apoptosis of osteoprogenitors may be responsible for increased osteogenesis in severely-injured patients.

Posttraumatic stress disorder (PTSD) may increase cardiovascular risk but the psychophysiological mechanisms involved are elusive. We hypothesized that proinflammatory activity is elevated in patients with PTSD as diagnosed by the Clinician Administered PTSD Scale (CAPS) interview. Plasma levels of proinflammatory C-reactive protein (CRP), interleukin (IL)-1beta, IL-6, and tumor necrosis factor (TNF)-alpha, and of anti-inflammatory IL-4 and IL-10 were measured in 14 otherwise healthy PTSD patients and in 14 age- and gender-matched healthy non-PTSD controls. Levels of TNF-alpha (p=0.038; effect size Cohen's d=0.58) and of IL-1beta (p=0.075, d=0.68) were higher in patients than in controls. CRP (d=0.10), IL-6 (d=0.18), IL-4 (d=0.42), and IL-10 (d=0.37) were not significantly different between groups. Controlling for traditional cardiovascular risk factors, mood, and time since trauma revealed lower IL-4 in patients than in controls (p=0.029) and rendered group differences in TNF-alpha and IL-1beta insignificant. In all subjects, TNF-alpha correlated with total (frequency and intensity) PTSD symptom cluster of re-experiencing (r=0.49, p=0.008), avoidance (r=0.37, p=0.050), and hyperarousal (r=0.42, p=0.026), and with PTSD total symptom score (r=0.37, p=0.054). Controlling for time since trauma attenuated these associations. The correlation between IL-1beta and total avoidance symptoms (r=0.42, p=0.028) became insignificant when controlling for anxiety and depression. IL-4 correlated with total hyperarousal symptoms (r=-0.38, p=0.047), and after controlling for systolic blood pressure and smoking status, with PTSD total symptom score (r=-0.41, p=0.035). PTSD patients showed a low-grade systemic proinflammatory state, which, moreover, was related to PTSD symptom levels suggesting one mechanism by which PTSD could contribute to atherosclerotic disease.

In human neutrophil granulocytes (PMN) endotoxin (LPS) leads to NF-κB activation and reduction of apoptosis. In this study we investigated whether transscription factors such as NF-κB, STAT3 or the proteasome regulate PMN survival after LPS-stimulation in PMN from patients with sepsis and healthy controls.

Pelvic fracture associated with liver trauma is not an uncommon injury combination in multiple trauma and is associated with high morbidity and mortality. The aim of this study was to examine the characteristics of this specific patient group, to describe the diagnostic and treatment protocols and finally to analyse risk factors associated with mortality. Data were collected over a 6-year period, ending in 2001. The pelvic injury was graded according to the Tile classification system and the hepatic injury was scored using the organ injury scale (OIS). Treatment protocol, associated injuries, complications, length of ICU/Hospital stay and mortality were recorded and analysed. A total of 140 patients (40% female) with a mean age of 35.1+/-15.9 years and a median ISS of 41 were included in this study. The overall mortality rate was 40.7%. Binomial logistic regression analysis revealed age, initial blood pressure, transfusion requirement as well as the severity of head, chest, spleen and liver injury as independent parameters predicting reduced survival rates. This deadly duo of injuries presents a challenge to the trauma surgeon. Rapid assessment and treatment is required to prevent death by haemorrhage. The presence of concomitant injuries renders the patient very sensitive to ongoing or additional physiological disturbance. The principles of 'damage control surgery' must be applied to avoid complications such as acute respiratory distress syndrome (ARDS) and multiple organ dysfunction syndrome (MODS).

An analysis of overdose cases with g-hydroxybutyrate (GHB) and its precursor g-butyrolactone (GBL) reported to the Swiss Toxicological Information Centre was recently published by Liechti and Kupferschmid in this journal [1]. We want to add to the evolving clinical picture of GHB and GBL intoxications by reporting a recent case from our institution presenting with a hitherto unknown severe sequelae of GBL intake. Case report: A 26-year-old nurse woke up in the morning before Christmas and realized that she was unable to move and feel here legs. She crawled to the phone, called for help and was admitted to the emergency room. Upon arrival she was afebrile, fully orientated and conscious. Her past medical history was unremarkable and she repeatedly denied any substance abuse besides moderate cigarette smoking. Physical examination showed sensomotoric, painful paraparesis of both legs at the level L2–3 without clinical signs of meningitis. Both feet were cold with week arterial pulses. Toxic neuropathy, traumatic and neoplastic nerve compression, and GuillainBarre syndrome were considered. However, computed tomography of the lumbar spine and liquor samples were normal whereas laboratory tests revealed elevated muscle enzymes (creatine kinase 135’905 U/l, myoglobulin >30’000 U/l, lactate dehydrogenase 4’114 U/l, aspartate aminotransferase 1’877 U/l), creatinine (166 mmol/l), blood urea nitrogen (10.2 mmol/l), phosphate (2.2 mmol/l) and potassium (5 mmol/l), moderate anaemia (Hb10 g/dl) and neutrophilia (9.14 103/ml). Drug screening in the urine revealed the presence of cocain, benzodiazepine and cannabis, but no amphetamines or opiates. The medical history was reiterated and the patient disclosed having sniffed cocaine at a party four days earlier for the first time in her life. Despite vigorous volume replacement acute renal failure developed necessitating continuous hemodiafiltration and both legs exhibited progressive bluish discoloration. A clinical diagnosis of acute compartment syndrome was made. Elevated intracompartmental pressures (25–47 mm Hg, normal

Background and Purpose: : Surgical hip dislocation by trochanteric flip osteotomy facilitates access to acetabular and femoral head fractures. Furthermore, it allows evaluation of cartilage damage and vascularity of the femoral head. In this study the potential benefits of this procedure for improved fracture management and for prognostic assessment were investigated. Patients and Methods: : From July 1997 to October 1999, 20 selected patients with displaced acetabular fractures (n = 12), femoral head fractures (n = 7), or combined injuries (n = 1) were included. Inclusion criteria for acetabular fractures were either displaced posterior wall fragments with cranial extension or complex acetabular fractures involving a displaced transverse fracture line. Open reduction and fixation of either complex acetabular fractures or femoral head fractures were carried out through Kocher-Langenbeck approach, trochanteric flip osteotomy, and complete surgical hip dislocation. Additionally, the extent of cartilage destruction and femoral head perfusion were assessed. Results: : Anatomic reduction (≤ 1 mm displacement) of acetabular fractures was achieved in 69% of patients and good reduction (≤ 3 mm) in 31%. In patients with acetabular fractures, severe cartilage destruction of the acetabulum was found in 38% and of the femoral head in 15%, while patients with isolated femoral head fractures revealed severe cartilage damage of the femoral head in 57%. Arterial bleeding from the femoral head, tested by drilling, was observed in all patients. Secondary dislocation of the trochanteric osteotomy occurred in one patient and made refixation necessary. Patients were reexamined at least 2 years after intervention. 77% of patients with acetabular fractures and all patients with femoral head fractures showed good or excellent results after 32.6 ± 6.1 months according to the functional score of D'Aubigné & Postel. Conclusion: : Surgical hip dislocation allows adequate reconstruction of complex acetabular and femoral head fractures and intraoperative evaluation of local cartilage damage and femoral head perfusion

Initial treatment of pelvic ring fractures with involvement of the iliosacral complex is directed at bleeding control and fixation of the pelvic ring. However, long-term outcome is determined by persisting neurological deficits, malunion of the posterior pelvic ring with low back pain, and urological lesions. Between 1991 and 2000, 173 patients with sacral fractures were treated at our institution. Sacral fractures as part of type B2 ("lateral compression") or type C ("vertical shear") pelvic ring fractures were treated conservatively, if dislocation was less than 1 cm. Fractures with a dislocation of more than 1 cm were treated operatively (n=33, 19%). A total of 112 patients were examined after an average of 4.9 years. Of the 39 patients with primary neurological deficits (35%) only 4 showed complete neurological recovery. Chronic low back pain was rarely observed (n=8, 7%) and only in type C injuries. The low incidence of chronic low back pain justifies conservative treatment of minimally (

Background Barbiturate coma is used in patients with traumatic brain injury whenever increases in intracranial pressure remain unresponsive to less aggressive therapeutic regimens. However, barbiturate-mediated neuroprotection correlates with lymphopenia, which increases the risk of infection. The mechanisms by which barbiturates lead to lymphopenia remain to be determined. Methods Freshly isolated human lymphocytes and Jurkat cells were incubated with the barbiturate thiopental for 24 and 48 h. Apoptosis was measured by fluorescein isothiocyanate-Annexin and propidium iodide staining, rhodamine 123 staining, and the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling method. Caspase-3 activity was detected by Western blot and substrate cleavage assay. Results Thiopental dose-dependently (5-500 microg/ml) increased apoptosis in Jurkat cells from basal levels (4.4 +/- 1.9%) to 29.7 +/- 2.8% after 24 h and 39.7 +/- 3.2% after 48 h, whereas in lymphocytes, thiopental-induced necrosis was observed. Parallel to apoptosis, thiopental dose-dependently increased caspase-3-like activity in Jurkat cells. However, the pan-caspase inhibitor z-VAD-fmk (20 microm) only marginally reduced thiopental-induced (250 microg/ml) apoptosis in Jurkat cells (20.2 +/- 2.5 to 17.2 +/- 2.5%) and necrosis in lymphocytes (39.2 +/- 7.5 to 30.7 +/- 14%). In contrast, anti-CD95-induced apoptosis in Jurkat cells (27.0 +/- 2.0%) was completely blocked by z-VAD-fmk (8.1 +/- 1.8%). Neither expression of CD95 on Jurkat cells nor pretreatment with a neutralizing anti-CD95 antibody influenced thiopental-induced apoptosis, indicating that thiopental induces apoptosis independently of the CD95 system. The nuclear factor kappaB inhibitor gliotoxin accelerated both thiopental- and CD95-mediated apoptosis, indicating a mutual control mechanism of thiopental- and CD95-induced apoptosis. Conclusions Thiopental directly induces cell death in lymphocytes and Jurkat cells by a CD95-independent mechanism.

Melatonin, secreted by the pineal gland, is a multifunctional agent which (i) protects tissues from damage through free radical scavenging and attenuates ischemia/reperfusion injury in organ grafts; (ii) acts synergistically with cellular antioxidants; and (iii) displays complex, dose-dependent immunoenhancing and suppressing effects in vitro and in vivo. We analyzed the immunomodulatory effect of melatonin on acute allograft rejection. Cardiac grafts were transplanted from LBNF1 to LEW rats and anastomosed to the abdominal great vessels. The effect of low-dose (LD; 20 mg/kg/day) and high-dose (HD; 200 mg/kg/day) melatonin treatment in recipients compared with untreated controls was investigated. HD melatonin therapy abrogated acute rejection, significantly prolonging allograft survival (mean survival: 12.3 +/- 1 days S.D., n = 8, P < 0.0001) compared with untreated controls, which rapidly reject the transplant (6.3 +/- 1 days n = 12). LD therapy did not extend survival significantly (7.3 +/- 1.1 days, n = 12). Allospecific IgM showed a significant decrease in animals receiving HD therapy versus untreated recipients at days 10 and 14 post-transplantation (P < 0.01), whereas in the LD group at day 10, a significant increase in allospecific IgM (P < 0.01) over the HD cohort was demonstrated. HD treatment markedly reduced lymphocyte proliferative capacity compared with controls and the LD group. HD melatonin treatment abrogated acute allograft rejection and significantly prolonged graft survival. Our results suggest an involvement of melatonin in humoral and cellular immune pathways following perfused organ transplantation. These findings may indicate a novel therapeutic approach, based on modulation of the neuroendocrine/immune axis through melatonin as a possible future immunosuppressant in organ transplantation.

Background Reduction of PMN apoptosis during sepsis contributes to the pathogenesis of multiple organ failure. Differential expression of Bcl-2 proteins, which participate in apoptosis regulation, may be responsible for the dysbalanced apoptosis seen in neutrophils from septic patients. In this study, expression of Mcl-1, Bid, Bcl-2, and Bax were investigated in septic neutrophils. Study design PMN (1 × 10 6 /mL) from septic patients (n = 16) or healthy volunteers (n = 10) were incubated with either lipopolysaccharide (1 μg/mL), agonistic CD95 antibody (100 ng/mL), or medium for 16 hours. Apoptosis was quantified in FACS after propidium iodine staining. Mcl-1, Bid, Bcl-2, and Bax mRNA expression was detected by reverse transcriptase–polymerase chain reaction and protein determined by Western blot analysis. Results Spontaneous apoptosis was significantly reduced in PMN from septic patients (28.8% versus 64.0% in controls). Mcl-1 protein levels decreased in patients after 16 hours but remained stable in controls. Mcl-1 mRNA was found in freshly isolated PMN from controls and patients but remained elevated only in patients. Bid protein level decreased significantly in control PMN undergoing apoptosis but differences were less prominent in septic patients. Bid mRNA was detected only in freshly isolated PMN. No Bcl-2 mRNA or protein was detected in neutrophils from patients or controls, and detectable Bax protein and mRNA levels remained unchanged in all samples. Conclusions Alterations of Bid and Mcl-1 protein in neutrophils may reflect the level of apoptosis. The upregulation of Mcl-1 mRNA in patients with sepsis suggests an active role for Mcl-1 in regulatiori of apoptosis during sepsis; Bax remains unchanged.

The dynamics of activated caspase-3 in neutrophilic granulocytes (PMN) were investigated under septic conditions. PMN (1 × 106) from healthy volunteers (n = 7) and septic patients (n = 5) were preincubated with LPS (1 βg/ml) for five hours. Then the proteasome inhibitor PSI (30 βM) was added and after one hour cells were stimulated with either agonistic anti-CD95 (αCD95) antibody (CH11, 100 ng/mL) or medium for another 16 hours. LPS preincubation reduced CD95-induced apoptosis to values comparable to spontaneous apoptosis (p < 0.05) and caspase-3 activity was also reduced. However, PSI, when given five hours after LPS, completely inhibited the LPS effect (p < 0.05) and restored apoptosis and caspase activity. The accumulation of ubiquitinated caspase-3 was seen in whole cell lysates from CD95-stimulated PMN after LPS or LPS/PSI-treatment. Thus, accelerated degradation of activated caspase-3 by ubiquitination may contribute to sepsis-induced apoptosis reduction of PMN. The long LPS-preincubation period suggests that reduction of CD95-induced apoptosis by LPS requires transcription and/or translation (⊡ Abbildung 1).

Reduction of neutrophil apoptosis represents a major cause for granulocytosis and increases the destructive potential of theses cells during systemic inflammatory response syndrome (SIRS) and sepsis. In this light, the role of protein kinases for the regulation of altered neutrophil apoptosis under infectious conditions was investigated. Neutrophils, obtained from patients with severe sepsis (n = 18), were incubated ex vivowith either LPS (1 microg/mL) or interferon-gamma (IFN-gamma; 10 ng/mL) for 16 h. Apoptosis was determined by propidium iodine (PI) staining of DNA fragments and was compared with the rate of spontaneous apoptosis. Tyrosine kinases were inhibited by herbimycin (1 microM), the mitogen-activated protein (MAP) kinase ERK was inhibited with PD98059 (50 microM), and p38 MAP kinase was inhibited with SB203580 (5 microM). Herbimycin reconstituted LPS-reduced apoptosis in neutrophils from controls (39.9 +/- 3.8%) and patients (20.8 +/- 2.8%) to levels seen in spontaneous apoptosis (70.9 +/- 2.8% and 40.7 +/- 3.7%, respectively). Inhibition of the ERK kinase yielded similar results, whereas SB203580 had no effect on LPS-reduced apoptosis. However, inhibition of p38 partially reconstituted IFN-gamma-reduced apoptosis (51.3 +/- 7.7% and 25.6 +/- 5.8%) and increased spontaneous apoptosis (82.4 +/- 3.3% and 42.0 +/- 5.8%) in controls and patients, respectively. Western blot analysis revealed phosphorylation of both MAP kinases by LPS, but not by IFN-gamma. Inhibition of MAP kinases did not augment neutrophil apoptosis in patients to the level seen in controls, indicating that other mechanisms must be involved in the regulation of neutrophil apoptosis. Although the ERK kinase regulates LPS-induced reduction of apoptosis, the p38 MAP kinase might be involved in IFN-gamma signaling and the feedback regulation of neutrophil apoptosis.

Aim/Background: Severe trauma causes a systemic inflammatory response which may lead to multiple organ failure (MOF). The aim of this study was to evaluate the influence of the injury pattern on the incidence and severity of posttraumatic inflammatory complications. Methods: A total of 1273 patients with an injury severity score (ISS) ≥ 9 points, age > 16 years, and survival of ≥ 3 days were included in this retrospective study. Outcomes included different grades of systemic inflammatory response syndrome (SIRS), sepsis, and MODS (Goris score), as well as mortality. Logistic regression analysis was performed by SPSS-software to test injury pattern as well as age, sex, and ISS as risk factors. Results: Severe non-infectious SIRS occurred in 23%, sepsis in 14% and severe MODS in 14% of enrolled patients. Severe traumatic head injury was seen in 49% and the overall mortality rate was 7%. Severe head injury and a high ISS represented the most potent risk factors for severe SIRS. Complex injuries of extremities, pelvis or abdomen, as well as the ISS and male sex were predictors for sepsis. Severe MODS could be predominantly observed in patients with high ISS, male sex, severe head or abdominal injuries. A high mortality was determined by severe head injury, high ISS and progressive age. Conclusion: Severe head injury dominates non-infectious systemic inflammation, multiple organ failure, as well as late mortality. Septic complications were determined by abdominal and skeletal injuries. The incidence of life-threatening inflammatory complications during the posttraumatic course can be associated with distinct injury pattern.

Introduction Anterior stabilization with cages/iliac bone graft and corpectomy in addition with posterior spondylodesis is the gold standard for the treatment of anterior unstable Magerl types A and B fractures of the thoracolumbar junction.1,2 The effect of temporary fixation on the intervertebral disc as well as on progression of kyphosis, especially after dorsal implant removal to unblock the caudal nonfused segment, is unclear. Materials and Methods Retrospective case series of all patients treated with posterior stabilization in combination with vertebroplasty/kyphoplasty between 2000 and 2010 with secondary implant removal 8 to 12 months after the index operation. All cases were assessed for loss of reduction, Cobb angle, and disc height after implant removal by anteroposterior and lateral radiographs. Results Overall 20 (m: 13; f: 7) (age: 40.9 ± 14.4 years) out of 59 patients treated with bridging dorsal instrumentation with transpedicular vertebroplasty underwent implant removal. Fractures were classified as A 3.21 in 15, A 3.1 in 3, and B 2.3 in 2 cases. The fracture location was Th12 in 5, L1 in 11, L2 and L3 in 2 cases. The implant removal was performed 9.6 ± 3.2 month after initial surgery. In all but one case increase of kyphosis was found 6 month later. The mean increase of kyphosis was 8 ± 6 degrees (max: 12 degrees; min: 0 degrees), mainly in the upper motion segment. Significant loss of disc height was found in the upper motion segment compared with before implant removal, whereas vertebral height remains stable. Age highly correlated to loss of reduction and disc height (r = 0.51). No differences between the fracture location and types were found. Conclusion After temporary fixation of the intervertebral disc by internal fixation an increase of kyphosis in the segment above the augmented/fractured vertebra is to be expected, especially because of degeneration of the disc above the affected vertebra. This effect is age dependent. In how far this has clinical relevance is topic of ongoing investigations. Disclosure of Interest None declared References Harris MB. The role of anterior stabilization with instrumentation in the treatment of thoracolumbar burst fractures. Orthopedics 1992;15(3):347–350 Mariotti AJ, Diwan AD. Current concepts in anterior surgery for thoracolumbar trauma. Orthop Clin North Am 2002;33(2):403–412

Loss of neurons after traumatic brain injury (TBI) might involve dysregulated apoptosis. Activation of caspase-3 is one hallmark of apoptosis. Therefore, caspase-3 activity (cleavage of DEVD-afc) was measured in cerebrospinal fluid (CSF) samples (n=113) from 27 patients with TBI at day 1 to 14 after trauma. Caspase-3 activity was detected in 31 (27.4%) CSF samples with highest values (> 5.5 microM/min) seen at day 2-5 after trauma. No caspase-3 activity was found in serum from patients or CSF from controls. The presence of activated caspase-3 in CSF suggests ongoing apoptotic processes during traumatic brain injury.

OBJECTIVES Evaluation of diagnostic and therapeutic workup in multiply injured patients with pelvic ring disruption and hemorrhagic shock. DESIGN Prospective study. PATIENTS Twenty consecutive multiply injured patients (ISS: 41.2 +/- 15.3 points) with pelvic ring disruption and hemorrhagic shock. INTERVENTION A C-clamp was used for primary stabilization of the pelvic ring instability. In patients with persistent or massive hemorrhage, laparotomy and pelvic packing were performed. Consecutive measurements of blood lactate levels during the early period after injury. MAIN OUTCOME MEASUREMENTS Lactate, mortality. RESULTS A C-clamp was applied in all patients within 57.4 +/- 30.6 minutes of arrival. Fourteen patients underwent laparotomy with pelvic packing for control of hemorrhage, three patients additional resuscitation thoracotomy (aortic clamping: n = 2). Four patients died of exsanguinating hemorrhage during the first 5.4 +/- 3.3 hours from arrival, one patient because of septic multi-organ failure twenty-three days after injury (total mortality: 5/20; 25 percent). Lactate levels at admission were elevated in all patients (5.1 +/- 2.6 mmol/l). Increased blood lactate levels (4.8 +/- 1.7 mmol/l) (+71 percent; p < 0.05) were observed in survivors undergoing laparotomy compared with survivors without laparotomy (2.8 +/- 1.1 mmol/l). In contrast, hemoglobin (7.0 +/- 2.6 g/dl versus 7.9 +/- 2.2 g/dl) and hematocrit (21.4 +/- 6.4 percent versus 23.2 +/- 6.8 percent) were similar in both groups. In patients who died during the first hours after admission, lactate levels were elevated (8.6 +/- 2.5 mmol/l) compared with survivors (4.2 +/- 1.8 mmol/l) and increased further. CONCLUSIONS Sequential measurements of blood lactate levels during the early period after injury may provide a more rapid and reliable estimation of true severity of hemorrhage than routinely used parameters. Pelvic packing in addition to pelvic ring fixation with a C-clamp allows for effective control of severe hemorrhage in multiply injured patients with pelvic ring disruption.

Aim/Background: Traumatic brain injury (TBI) is the leading cause of death in injured patients [1]. Secondary brain edema following TBI often determines morbidity and mortality in these patients. Intracranial pressure (ICP) can be reduced by intravenous administration of barbiturate [2]. However, this therapy is complicated by a disturbed immunocompetence with leukopenia and an increased infection rate [3]. The aim of this study was to investigate the influence of barbiturate on neutrophil (PMN) apoptosis. Methods: PMN from six healthy volunteers and patients with severe TBI without (n = 5) or with barbiturate coma (n = 5) were isolated by density gradient centrifugation and incubated for 16 h with or without barbiturate (thiopental; 250 µg/ml). To test whether the ability of cells to undergo apoptosis was disturbed, PMN were incubated with an agonistic anti-Fas mAb (CH11; 100 ng/ml). PMN apoptosis was measured by propidium iodide staining using flow cytometry [4]. Results: Spontaneous PMN apoptosis in patients with severe TBI (11.2 ± 3.1%) was significantly reduced compared to healthy volunteers (72.3 ± 2.9%) and patients with severe TBI and barbiturate coma (43.1 ± 7.7%). Thiopental induced PMN apoptosis in all groups. Its effect was additive to Fas-activated apoptosis. Conclusion: Barbiturate induces neutrophil apoptosis. The increased infection rate of patients with severe TBI and barbiturate coma may be a consequence of barbiturate-induced neutrophil apoptosis and neutropenia.

To compare procalcitonin (PCT) plasma levels of injured patients with the incidence and severity of systemic inflammatory response syndrome (SIRS), infection, and multiple organ dysfunction syndrome (MODS) and to assess the predictive value of PCT for these posttraumatic complications.Retrospective study comparing patients with mechanical trauma in terms of severity of injury, development of infectious complications, and organ dysfunctions.Level I trauma center with emergency room, intensive care unit, and research laboratory.Four hundred five injured patients with an Injury Severity Score ofor =9 points were enrolled in this study from January 1994 to February 1996.Blood samples were collected on the day of admission and on days 1, 3, 5, 7, 10, 14, and 21 thereafter.We determined PCT serum levels using a specific immunoluminometric assay. We retrospectively evaluated the occurrence of SIRS, sepsis, and MODS using patients' charts. Mechanical trauma led to increased PCT plasma levels dependent on the severity of injury, with peak values on days 1 and 3 (p.05) and a continuous decrease within 21 days after trauma. Patients who developed SIRS demonstrated a significant (p.05) increase of peak PCT plasma levels compared with patients without SIRS. The highest PCT plasma concentrations early after injury were observed in patients with sepsis (6.9+/-2.5 ng/mL; day 1) or severe MODS (5.7+/-2.2 ng/mL; day 1) with a sustained increase (p.05) for 14 days compared with patients with an uneventful posttraumatic course (1.1+/-0.2 ng/mL). Moreover, these increased PCT plasma levels during the first 3 days after trauma predicted (p.0001; logistic regression analysis) severe SIRS, sepsis, and MODS.These data indicate that PCT represents a sensitive and predictive indicator of sepsis and severe MODS in injured patients. Routine analysis of PCT levels seems to aid early recognition of these posttraumatic complications. Thus, PCT may represent a useful marker to monitor the inflammatory status of injured patients at risk.

Die veminderte Apoptose von neutrophilen Granulozyten (PMN) wahrend der Sepsis fuhrt zu deren Akkumulation mit einer erhohten Freisetzung von zytotoxischen Mediatoren [1]. Intrazellulare Zystein-Proteasen (Kaspasen), die uber die Signaltransduktion aktiviert werden, sind fur die Regulation der PMN-Apoptose von groser Bedeutung [2]. Es war Ziel dieser Studie, die Kaspasenaktivitat in PMN and deren Regulation zu untersuchen.

Angiogenesis is a key component of the repair mechanisms triggered by tissue injury. Vascular endothelial growth factor (VEGF) is an important mediator of angiogenesis, as it acts directly and specifically on endothelial cells. VEGF produced locally in regenerating tissue may spill over into the systemic circulation, and measuring levels of circulating VEGF may allow monitoring of angiogenesis. To determine whether circulating VEGF is increased after severe injury, we measured concentrations of VEGF in serial serum samples of 23 mechanical burn patients, 55 patients with multiple trauma and 56 healthy normal controls, using a newly established ELISA assay. In burn patients, serum VEGF was increased on day 1 (369.4 ± 88.0 pg/ml) and on day 3 (452.0 ± 65.3 pg/ml), reached highest levels on day 14 (1809.5 ± 239.7 pg/ml) and was still elevated on day 21 post-burn (1339.8 ± 208.7 pg/ml) (mean ± SEM, p

Neutrophile Granulozyten (PMN) spielen fur das Organversagen wahrend der Sepsis eine wichtige Rolle. Durch die Hemmung der Apoptose („programmierter Zelltod“) kommt es zu einer Akkumulation von PMN mit einer uberschiesenden und persistierenden Sekretion von gewebetoxischen Metaboliten (Proteasen, Sauerstoffradikale). In vitro Untersuchungen mit eosinophilen Granulozyten gesunder Probanden zeigten, das die Apoptose von PMN masgeblich durch die Tyrosinphosphorylation reguliert wird [1, 2]. Es ist nicht bekannt, ob Veranderungen der Tyrosinphosphorylation fur die Endotoxin induzierte Hemmung der Apoptose verantwortlich sind.

Interleukin-10 (IL-10) markedly inhibits lymphocyte and phagocytic functions, which are essential for an adequate immune response to invading microbes. Although various animal and clinical studies revealed an increased release of IL-10 during sepsis, alterations of circulating IL-10 after injury and potential relationships to severity of injury and clinical outcome are unknown. Injured patients (n = 417) showed elevated (p0.001) IL-10 levels throughout the observation period of 21 days compared with healthy volunteers (n = 137). Patients with severe injury (Injury Severity Scoreor = 25 points) demonstrated significantly increased IL-10 levels compared with patients with minor trauma (Injury Severity Score25 points). Patients who died from injury or developed posttraumatic complications (sepsis, multiple organ dysfunction syndrome) revealed elevated IL-10 levels in comparison with injured patients with uneventful posttraumatic course. Thus, trauma causes an enhanced release of IL-10 dependent on the severity of injury. Because increased IL-10 levels are significantly related to posttraumatic complications, IL-10 may be involved in their pathogenesis.

When the cell surface molecule Fas is triggered by its agonist Fas ligand the result is apoptosis of these cells and tissue destruction. To elucidate the pathophysiological relevance of Fas ligand in patients with cerebral oedema caused by trauma, we examined its concentrations in cerebrospinal fluid in 18 patients using specific ELISA. Serum and cerebrospinal fluid from healthy people and injured patients without head trauma did not contain detectable Fas ligand. In contrast, cerebrospinal fluid from patients with severe brain injury contained high concentrations of Fas ligand without detectable concentrations in serum. Soluble Fas ligand concentrations in cerebrospinal fluid correlated significantly with severity of brain injury. The Fas-Fas ligand-system may have a pivotal role in causing oedema and local tissue destruction in the brain after severe head injury.

Background : Excessive release of proinflammatory cytokines has been involved in pathogenesis of acute respiratory distress syndrome. Design : Since injured patients with chest trauma reveal a high risk for posttraumatic acute respiratory distress syndrome, local and systemic release of proinflammatory cytokines and their naturally occurring inhibitors were determined in the early posttraumatic period. Materials and Methods : Proinflammatory and anti-inflammatory mediators were measured in plasma and bronchoalveolar lavage fluid (BALF) from 16 patients with multiple injuries including severe chest injury (Injury Severity Score of 34.4 ± 2.3 points) and compared with healthy volunteers (n = 17). Results : Tumor necrosis factor-α was detectable neither in plasma nor in BALF. Interleukin-1β and interleukin-8 were significantly increased in BALF from injured patients, while plasma levels were similar in both groups. Soluble tumor necrosis factor receptors p55 and p75 and interleukin-lra were markedly elevated in plasma (p ≤ 0.01) and BALF (p ≤ 0.001) from injured patients compared with controls. Conclusion : Highly increased concentrations of proinflammatory cytokines in BALF, but not in circulation, indicate a strong local inflammatory response early after multiple injuries combined with chest injury rather than severe systemic inflammation. In contrast, anti-inflammatory mechanisms seem to be activated locally and systemically.

Background: Obesity is a growing problem in industrial nations. The aim of this study was to determine the relationship between the body mass index (BMI) and the pattern of injury after polytrauma. Methods: This retrospective study included 651 patients with an injury severity score (ISS) ≥16 and aged ≥16 years who were subdivided into three groups: BMI < 25 kg/m2, BMI 25–30 kg/m2, and BMI > 30 kg/m2. The Abbreviated Injury Scale (AIS) was used to quantify the injuries in the different anatomical regions. The Murray score was assessed at admission and at its maximum during hospitalization to evaluate pulmonary problems. Data are presented as means ± standard errors of the means. One way analysis of variance, χ2 test and Kruskal-Wallis test were used for the analyses and the significance level was set at p < 0.05. Results: The AIS of the thorax was 3.2 ± 0.1 in the BMI < 25 kg/m2 group, 3.3 ± 0.1 in the BMI 25–30 kg/m2 group, and 2.8 ± 0.2 in the BMI > 30 kg/m2 group; p < 0.05. The Murray score at admission increased significantly with increasing BMI (0.8 ± 0.8 for BMI < 25 kg/m2, 0.9 ± 0.9 for BMI 25–30 kg/m2, and 1.0 ± 0.8 for BMI > 30 kg/m2; p < 0.05) as was the maximum Murray score during hospitalization (1.2 ± 0.9 for BMI < 25 kg/m2, 1.6 ± 1.0 for BMI 25–30 kg/m2, and 1.5 ± 0.9 for BMI > 30 kg/m2; p < 0.001). The number of ventilator days was also elevated significantly with increasing BMI (5.9 ± 0.4 for BMI < 25 kg/m2, 7.7 ± 0.8 for BMI 25–30 kg/m2, and 7.9 ± 1.6 for BMI > 30 kg/m2; p < 0.05). Conclusion: Overweight and obesity lead to a higher incidence of thoracic trauma in a polytrauma situation and may additionally handicap ventilation in an obstructive manner.

Excessive synthesis of proinflammatory cytokines [tumor necrosis factor (TNF)-alpha and interleukin (IL)-1 beta] after trauma has been correlated with poor outcome. Recently, naturally occurring inhibitors of TNF-alpha and IL-1 beta have been characterized such as soluble TNF receptors (sTNFRs) and IL-1 receptor antagonist (IL-1ra). The present study was undertaken to determine whether injury results in a rise of circulating sTNFRs and IL-1ra. If so, whether plasma levels of these anti-inflammatory mediators correlate with severity of injury and clinical outcome of these patients. Injured patients (n = 213) showed significantly increased sTNFR and IL-1ra plasma levels throughout the observation period of 14 days, compared with healthy volunteers (n = 127). Patients with severe injury (Injury Severity Score > 16 points) revealed higher levels (p < 0.05) of sTNFRs and IL-1ra than patients with minor trauma (Injury Severity Score < or = 16 points). Patients who died from injury demonstrated increased (p < 0.05) sTNFR p55 and IL-1ra plasma levels, compared with survivors. Thus, anti-inflammatory mechanisms are activated after trauma dependent on severity of injury. Because increased plasma levels of anti-inflammatory reacting proteins portended poorly for patient survival, these mediators may contribute to prediction of outcome after severe injury.

INTRODUCTION: Maintaining arterial blood glucose within tight limits is beneficial in critically ill patients. Upper and lower limits of detrimental blood glucose levels must be determined. METHODS: In 69 patients with severe traumatic brain injury (TBI), cerebral metabolism was monitored by assessing changes in arterial and jugular venous blood at normocarbia (partial arterial pressure of carbon dioxide (paCO2) 4.4 to 5.6 kPa), normoxia (partial arterial pressure of oxygen (paO2) 9 to 20 kPa), stable haematocrit (27 to 36%), brain temperature 35 to 38 degrees C, and cerebral perfusion pressure (CPP) 70 to 90 mmHg. This resulted in a total of 43,896 values for glucose uptake, lactate release, oxygen extraction ratio (OER), carbon dioxide (CO2) and bicarbonate (HCO3) production, jugular venous oxygen saturation (SjvO2), oxygen-glucose index (OGI), lactate-glucose index (LGI) and lactate-oxygen index (LOI). Arterial blood glucose concentration-dependent influence was determined retrospectively by assessing changes in these parameters within pre-defined blood glucose clusters, ranging from less than 4 to more than 9 mmol/l. RESULTS: Arterial blood glucose significantly influenced signs of cerebral metabolism reflected by increased cerebral glucose uptake, decreased cerebral lactate production, reduced oxygen consumption, negative LGI and decreased cerebral CO2/HCO3 production at arterial blood glucose levels above 6 to 7 mmol/l compared with lower arterial blood glucose concentrations. At blood glucose levels more than 8 mmol/l signs of increased anaerobic glycolysis (OGI less than 6) supervened. CONCLUSIONS: Maintaining arterial blood glucose levels between 6 and 8 mmol/l appears superior compared with lower and higher blood glucose concentrations in terms of stabilised cerebral metabolism. It appears that arterial blood glucose values below 6 and above 8 mmol/l should be avoided. Prospective analysis is required to determine the optimal arterial blood glucose target in patients suffering from severe TBI.