Obese trauma patients are at increased risk of early hypovolemic shock: a retrospective cohort analysis of 1,084 severely injured patients.

INTRODUCTION: Morbid obesity and its consequences are considered risk factors for adverse outcome in trauma, although the pathophysiologic mechanisms are incompletely understood. The aim of this study was to compare initial resuscitation, treatment, and short-term outcome of severely injured patients by body mass index (BMI). METHODS: A total of 1,084 severely injured patients with an injury severity score of 16 or greater were enrolled between 1996 and 2009 and grouped according to BMI. Their course of treatment and in-hospital outcome were analyzed by univariate and multivariate comparison. RESULTS: Of these patients, 603 (55.6%) were of normal weight with a BMI between 18.5 and 24.9, 361 (33.3%) had BMI values between 25 and 29.9, and 90 patients (8.3%) were obese (BMI ≥ 30). Thirty patients (2.8%) had BMI levels below 18.5. All groups were comparable with respect to injury severity, initial resuscitation, and time to ICU admission. There was a tendency towards higher mortality in obese patients (mortality 24.4%) and also overweight patients (mortality 18.8%) when compared with patients with a normal BMI (mortality 16.6%). Obese patients showed the highest mortality on day 0 (8.9% vs. 2.8% in the normal-weight group, P = 0.023), mostly due to persistent shock (6.7%). When corrected for BMI, obese patients are provided significantly lower volumes of intravenous fluids during the initial resuscitation period. CONCLUSION: In contrast to the mostly American literature, only a low percentage of trauma patients at a European trauma center are obese. These patients are at risk of higher mortality from persistent hemorrhagic shock in the initial phase after trauma, which may potentially be related to relative hypovolemia during the resuscitation period. In the later course of treatment, no significant differences exist with respect to specific complications, hospital stay, or in-hospital mortality.

Compartment pressure of the rectus sheath accurately reflects intra-abdominal pressure in a porcine model.

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. 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+/-2.5 kg). INTERVENTIONS: Stepwise increase and decrease of IAP by means of CO(2) 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 12 mm Hg and 30 mm Hg (bias -0.5 mm Hg, lower and upper limits of agreement (LLA/ULA) -3.5/2.5 mm Hg). FVP (bias -0.3 mm Hg, LLA/ULA -2.3/1.6 mm Hg) and IVP (bias 0.4 mm Hg, LLA/ULA -2.1/2.9 mm Hg) demonstrated similar results compared with direct IAP measurement. Agreement was worse for all indirect IAP measurement techniques for IAP<12 mm Hg. CONCLUSIONS: CPRS accurately reflects IAP for IAP> or =12 mm Hg. Accuracy is similar to established indirect IAP measurement techniques.

Intra-abdominal pressure development after different temporary abdominal closure techniques in a porcine model.

BACKGROUND: Decompressive laparotomy followed by temporary abdominal closure (TAC) is an established prophylaxis and treatment for abdominal compartment syndrome. The herein presented study aimed at the comparison of volume reserve capacity and development of intra-abdominal hypertension after forced primary abdominal closure and different TAC techniques in a porcine model. METHODS: Eight anesthesized and mechanically ventilated domestic pigs underwent a standardized midline laparotomy. A bag was placed into the abdominal cavity. Before abdominal closure, the bag was prefilled with 3,000 mL water to simulate increased intra-abdominal volume. The intra-abdominal pressure (IAP) was then increased in 2 mm Hg steps up to 30 mm Hg by adding volume (volume reserve capacity) to the intra-abdominal bag. Volume reserve capacity with the corresponding IAP were analyzed and compared for primary abdominal closure, bag silo closure, a zipper system, and vacuum-assisted closure (VAC) with different negative pressures (-50, -100, and -150 mm Hg). Hemodynamic and pulmonary parameters were monitored throughout the experiment. RESULTS: Volume reserve capacity was the highest for bag silo closure followed by the zipper system and VAC with primary abdominal closure providing the least volume reserve capacity in the whole IAP range. Of interest, VAC -50 mm Hg resulted in a lower volume reserve capacity when compared with VAC -100 and -150 mm Hg. Pulmonary and hemodynamic parameters demonstrated no significant differences between primary abdominal closure and the evaluated TAC techniques at all IAP levels. CONCLUSIONS: The present experimental in vivo study indicates that bag silo closure and zipper systems may be favorable TAC techniques after decompressive laparotomy. In contrast, the VAC techniques resulted in lower volume reserve capacity and therefore may bear an increased risk for recurrent intra-abdominal hypertension in the initial phase after decompressive laparotomy.

Microdialysis of the rectus abdominis muscle for early detection of impending abdominal compartment syndrome.

OBJECTIVE: To investigate whether microdialysis is capable of assessing metabolic derangements during intra-abdominal hypertension (IAH), and whether monitoring of the rectus abdominis muscle (RAM) by microdialysis represents a reliable approach in the early detection of organ dysfunctions in abdominal compartment syndrome (ACS). DESIGN: Prospective, randomized, controlled animal study. SETTING: University animal research facility. SUBJECTS: Fifteen isoflurane-anesthetized and mechanically ventilated Sprague-Dawley rats. INTERVENTIONS: IAH of 20 mmHg was induced for 3 h and followed by decompression and reperfusion for another 3-h period (n = 10). Five sham-operated animals served as controls. Microdialysis was performed in the anterior gastric wall, liver, kidney, and RAM. The anterior cervical muscles served as distant reference. Glucose, lactate, pyruvate, and glycerol was analyzed throughout the 6-h experiment. MEASUREMENTS AND MAIN RESULTS: Prolonged IAH induced significant cardiopulmonary dysfunction and persistent abdominal organ injury. Microdialysis revealed a significant increase of lactate/pyruvate and glycerol in kidney, intestine and liver, indicating ischemia, energy failure, and cell membrane damage. In addition, at 3 h IAH glucose was significantly decreased in all organs studied. The distant reference did not show any alteration of lactate/pyruvate, glycerol, and glucose over the entire 6-h observation period. In contrast to the other organs, microdialysis of the RAM showed an early and more pronounced increase of lactate, lactate/pyruvate and glycerol already at 1 h IAH. It is noteworthy that lactate, glycerol, and glucose did not completely recover upon decompression of IAH. CONCLUSIONS: Our data suggest that continuous microdialysis in the RAM may represent a promising tool for early detecting IAH-induced metabolic derangements.

The use of vacuum assisted closure (VAC) in soft tissue injuries after high energy pelvic trauma.

BACKGROUND: Application of vacuum-assisted closure (VAC) in soft tissue defects after high-energy pelvic trauma is described as a retrospective study in a level one trauma center. MATERIALS AND METHODS: Between 2002 and 2004, 13 patients were treated for severe soft tissue injuries in the pelvic region. All musculoskeletal injuries were treated with multiple irrigation and debridement procedures and broad-spectrum antibiotics. VAC was applied as a temporary coverage for defects and wound conditioning. RESULTS: The injuries included three patients with traumatic hemipelvectomies. Seven patients had pelvic ring fractures with five Morel-Lavallee lesions and two open pelviperineal trauma. One patient suffered from an open iliac crest fracture and a Morel-Lavallee lesion. Two patients sustained near complete pertrochanteric amputations of the lower limb. The average injury severity score was 34.1 +/- 1.4. The application of VAC started in average 3.8 +/- 0.4 days after trauma and was used for 15.5 +/- 1.8 days. The dressing changes were performed in average every 3 days. One patient (8%) with a traumatic hemipelvectomy died in the course of treatment due to septic complications. CONCLUSION: High-energy trauma causing severe soft tissues injuries requires multiple operative debridements to prevent high morbidity and mortality rates. The application of VAC as temporary coverage of large tissue defects in pelvic regions supports wound conditioning and facilitates the definitive wound closure.

Lateral impact in closed head injury: a substantially increased risk for diffuse axonal injury--a preliminary study.

OBJECTIVE: Assessment, whether location of impact causing different facial fracture patterns was associated with diffuse axonal injury in patients with severe closed head injury. METHODS: Retrospectively all patients referred to the Trauma Unit of the University Hospital of Zurich, Switzerland between 1996 and 2002 presenting with severe closed head injuries (Abbreviated Injury Scale (AIS) (face) of 2-4 and an AIS (head and neck) of 3-5) were assessed according to the Glasgow Coma Scale (GCS) and the Injury Severity Score (ISS). Facial fracture patterns were classified as resulting from frontal, oblique or lateral impact. All patients had undergone computed tomography. The association between impact location and diffuse axonal injury when correcting for the level of consciousness (using the Glasgow scale) and severity of injury (using the ISS) was calculated with a multivariate regression analysis. RESULTS: Of 200 screened patients, 61 fulfilled the inclusion criteria for severe closed head injury. The medians (interquartile ranges 25;75) for GCS, AIS(face) AIS(head and neck) and ISS were 3 (3;13), 2 (2;4), 4 (4;5) and 30 (24;41), respectively. A total of 51% patients had frontal, 26% had an oblique and 23% had lateral trauma. A total of 21% patients developed diffuse axonal injury (DAI) when compared with frontal impact, the likelihood of diffuse axonal injury increased 11.0 fold (1.7-73.0) in patients with a lateral impact. CONCLUSIONS: Clinicians should be aware of the substantial increase of diffuse axonal injury related to lateral impact in patients with severe closed head injuries.

Measurement of compartment pressure of the rectus sheath during intra-abdominal hypertension in rats.

OBJECTIVE: 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). DESIGN AND SETTING: Prospective experimental study with in vivo pressure measurements at the Institute for Clinical and Experimental Surgery, University of Saarland. ANIMALS: Sprague-Dawley rats. INTERVENTIONS: Stepwise increase and decrease in IAP with continuous measurement of the correspondent CPRS. MEASUREMENTS AND RESULTS: Physiological IAP (2 mmHg) and CPRS (6 mmHg) showed a statistically significant difference. Stepwise elevation in IAP was associated with a simultaneous increase in CPRS. Accordingly, stepwise decompression of IAP resulted in a stepwise decrease in CPRS. Under both conditions Bland-Altman analysis comparing IAP to correspondent CPRS showed a very good agreement for IAP at or above 12 mmHg. In addition, closure of the overlaying subcutaneous tissue and skin did not affect CPRS or its correlation with IAP. CONCLUSIONS: CPRS accurately reflects IAP for IAP of 12 mmHg or higher. Thus CPRS measurements may represent a novel approach for diagnosis and monitoring of IAH.

Cbfa-1 (Runx-2) and osteocalcin expression by human osteoblasts in heparin osteoporosis in vitro.

Heparin may cause adverse effects on bone formation following long-term application. The exact pathomechanism is unclear, but in vitro data suggest an impaired osteoblast function. The transcription axis of Cbfa-1 (Runx-2) and osteocalcin is crucial in maintaining an equilibrium of bone formation and resorption in vivo. We used a human osteoblast cell culture model to further investigate the effect of heparin (low-molecular-weight heparin, dalteparin) on the expression of these two regulators of osteoblast differentiation. At high doses, dalteparin caused a significant inhibition of both osteocalcin and Cbfa-1 expression in vitro. Our data support the hypothesis of a direct inhibition of osteoblast function underlying heparin osteoporosis.

V.A.C. instillation: in vitro model. Part 2.

The behavior of a liquid in foam in the course of the V.A.C. instillation was investigated in an in vitro model by visualization using an aqueous color solution and by a quantitative determination of changing concentration of Ringerlactate solution.

Timing of fixation of major fractures in blunt polytrauma: role of conventional indicators in clinical decision making.

Grading of the clinical status in patients with multiple trauma is important regarding the treatment plan. In recent years, 4 different clinical conditions have been described: stable, borderline, unstable, in extremis. Clinical parameters have been widely used in patients with penetrating injuries, and 3 categories were found to be important: shock, hypothermia, coagulopathy. However, in blunt trauma patients, the role of conventional parameters for decision making regarding the timing of fracture treatment is poorly described. After blunt trauma, additional factors seem to play a role, because the injuries affect multiple body regions. These additional factors are summarized under the term, "soft-tissue injuries," which may include the soft tissues of the extremities, lung, abdomen, and pelvis. The study describes four pathophysiologic cascades that are relevant to the clinical conditions listed above. Threshold values for separation of the patient conditions are documented, leading to a staged surgical strategy.

The chemokine fractalkine in patients with severe traumatic brain injury and a mouse model of closed head injury.

The potential role of the chemokine Fractalkine (CX3CL1) in the pathophysiology of traumatic brain injury (TBI) was investigated in patients with head trauma and in mice after experimental cortical contusion. In control individuals, soluble (s)Fractalkine was present at low concentrations in cerebrospinal fluid (CSF) (12.6 to 57.3 pg/mL) but at much higher levels in serum (21,288 to 74,548 pg/mL). Elevation of sFractalkine in CSF of TBI patients was observed during the whole study period (means: 29.92 to 535.33 pg/mL), whereas serum levels remained within normal ranges (means: 3,100 to 59,159 pg/mL). Based on these differences, a possible passage of sFractalkine from blood to CSF was supported by the strong correlation between blood-brain barrier dysfunction (according to the CSF-/serum-albumin quotient) and sFractalkine concentrations in CSF (R = 0.706; P < 0.01). In the brain of mice subjected to closed head injury, neither Fractalkine protein nor mRNA were found to be augmented; however, Fractalkine receptor (CX3CR1) mRNA steadily increased peaking at 1 week postinjury (P < 0.05, one-way analysis of variance). This possibly implies the receptor to be the key factor determining the action of constitutively expressed Fractalkine. Altogether, these data suggest that the Fractalkine-CX3CR1 protein system may be involved in the inflammatory response to TBI, particularly for the accumulation of leukocytes in the injured parenchyma.

Elevated intracranial IL-18 in humans and mice after traumatic brain injury and evidence of neuroprotective effects of IL-18-binding protein after experimental closed head injury.

Proinflammatory cytokines are important mediators of neuroinflammation after traumatic brain injury. The role of interleukin (IL)-18, a new member of the IL-1 family, in brain trauma has not been reported to date. The authors investigated the posttraumatic release of IL-18 in murine brains following experimental closed head injury (CHI) and in CSF of CHI patients. In the mouse model, intracerebral IL-18 was induced within 24 hours by ether anesthesia and sham operation. Significantly elevated levels of IL-18 were detected at 7 days after CHI and in human CSF up to 10 days after trauma. Published data imply that IL-18 may play a pathophysiological role in inflammatory CNS diseases; therefore its inhibition may ameliorate outcome after CHI. To evaluate the functional aspects of IL-18 in the injured brain, mice were injected systemically with IL-18-binding protein (IL-18BP), a specific inhibitor of IL-18, 1 hour after trauma. IL-18BP-treated mice showed a significantly improved neurological recovery by 7 days, accompanied by attenuated intracerebral IL-18 levels. This demonstrates that inhibition of IL-18 is associated with improved recovery. However, brain edema at 24 hours was not influenced by IL-18BP, suggesting that inflammatory mediators other than IL-18 induce the early detrimental effects of intracerebral inflammation.

Prolonged intrathecal release of soluble Fas following severe traumatic brain injury in humans.

The mechanisms underlying cell death following traumatic brain injury (TBI) are not fully understood. Apoptosis is believed to be one mechanism contributing to a marked and prolonged neuronal cell loss following TBI. Recent data suggest a role for Fas (APO-1, CD95), a type I transmembrane receptor glycoprotein of the nerve growth factor/tumor necrosis factor superfamily, and its ligand (Fas ligand, FasL) in apoptotic events in the central nervous system. A truncated form of the Fas receptor, soluble Fas (sFas) may indicate activation of the Fas/FasL system and act as a negative feedback mechanism, thereby inhibiting Fas mediated apoptosis. Soluble Fas was measured in cerebrospinal fluid (CSF) and serum of 10 patients with severe TBI (GCS< or =8) for up to 15 days post-trauma. No sFas was detected in CSF samples from patients without neurological pathologies. Conversely, after TBI 118 out of 120 CSF samples showed elevated sFas concentrations ranging from 56 to 4327 mU/ml. Paired serum samples showed above normal (8.5 U/ml) sFas concentrations in 5 of 10 patients. Serum levels of sFas were always higher than CSF levels. However, there was no correlation between concentrations measured in CSF and in serum (r(2)=0.078, p=0.02), suggesting that the concentrations in the two compartments are independently regulated. Also, no correlation was found between sFas in CSF and blood brain barrier (BBB) dysfunction as assessed by the albumin CSF/serum quotient (Q(A)), and concentrations of the cytotoxic cytokine tumor necrosis factor-alpha in CSF, respectively. Furthermore, there was no correlation with two markers of immune activation (soluble interleukin-2 receptor and neopterin) in CSF. Maximal CSF levels of sFas correlated significantly (r(2)=0.8191, p<0.001) with the early peaks of neuron-specific enolase in CSF (a marker for neuronal cell destruction), indicating that activation of the Fas mediated pathway of apoptosis may be in part the direct result of the initial trauma. However, the prolonged elevation of sFas in CSF may be caused by the ongoing inflammatory response to trauma and delayed apoptotic cell death.

Increased expression of toll-like receptor-2 and -4 on leukocytes from patients with sepsis.

The reduced responsiveness of monocytes or granulocytes toward endotoxin (endotoxin tolerance) during sepsis may depend on Toll-like receptors (TLR). The expression of TLR-2 and TLR-4 was measured on neutrophils (PMN) and monocytes from patients with sepsis (n = 21) or healthy controls (n = 12). Leukocytes (1 x 10/mL) were incubated at 37 degrees C with or without a TLR-4 (LPS 1 microg/mL) or a TLR-2 ligand (MALP-2 2 nM). Surface expression of TLR-2 and TLR-4 at 0, 4, and 16 h was determined in FACS after staining with specific antibodies. The release of IL-8 and TNF-alpha was measured by ELISA. Freshly isolated PMN from patients with sepsis exhibited significantly (P < 0.05) higher mean fluorescence for TLR-2 (78.0 +/- 18.6) and TLR-4 (11.4 +/- 2.3) than controls (12.8 +/- 2.2 and 2.3 +/- 0.4). Similarly, monocytes from patients exhibited higher TLR-2 and TLR-4 expression (300.8 +/- 40.6 and 92.7 +/- 12.1) than cells from controls (149.5 +/- 27.1 and 52.2 +/- 7.6). In patients with sepsis, expression of TLR-2 and TLR-4 on PMN increased during 16 h of incubation (106.2 +/- 22.1 and 34.5 +/- 5.3), whereas it remained unchanged in controls (19.3 +/- 6.1 and 5.4 +/- 1.9). Incubation with LPS or MALP-2 had no effect on TLR-4 or TLR-2 expression in cells from either controls or patients. Despite increased TLR expression in cells from patients with sepsis, the endotoxin-induced release of TNF-alpha and IL-8 was indistinguishable from that in controls. Therefore, the endotoxin tolerance seen in patients with sepsis does not depend solely on TLR-2 or TLR-4 expression, and other mechanisms must be involved.

Activation of mitogen-activated protein kinases during granulocyte apoptosis in patients with severe sepsis.

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.

Osteoblasts response to allogenic and xenogenic solvent dehydrated cancellous bone in vitro.

The present in vitro study investigates the cellular interaction of primary human osteoblasts with human and bovine solvent dehydrated cancellous bone (SDCB) discs. These are bio-implants from solvent dehydrated, gamma-irradiated preserved human and bovine cancellous bone, pre-treated to remove all cells, genetic components and water soluble proteins. Primary human osteoblasts were harvested from cancellous chips of trauma patients undergoing osteosynthesis with bone grafting from the iliac crest. All patients provided informed consent. The present investigation tested proliferation, synthesis of phenotypic marker, and morphology of primary cultured human osteoblasts on SDCB in vitro. The total protein and collagen type 1 content could not be revealed, due to the inherent naturally occurring protein content in these two bio-implants. In conclusion, our in vitro results suggest that SDCB may be a suitable bone substitute which provides a well structured and biocompatible scaffold for ingrowing human osteoblasts.

Endotoxin reduces CD95-induced neutrophil apoptosis by cIAP-2-mediated caspase-3 degradation.

BACKGROUND: Reduced apoptosis of neutrophil granulocytes (PMN) contributes to pathogenesis of systemic inflammatory response syndrome, sepsis, and multiple organ dysfunction syndrome. The intracellular inhibitor of apoptosis proteins has been shown to inhibit activated caspase-3. We investigated the turnover dynamics of cIAP-2 mRNA and caspase-3 protein in a neutrophil ex vivo model of sepsis. STUDY DESIGN: PMN (1 x 10(6)/mL) from 7 healthy volunteers were preincubated with endotoxin (lipopolysaccharide [LPS], 1 microg/mL) for 5 hours, followed by an additional hour with or without the proteasome inhibitor (30 microM), before incubation with or without agonistic CD95 antibody (100 ng/mL) for another 16 hours. Apoptosis was quantified by Annexin-V and propidium iodide staining by flow cytometry (using a fluorescence-activated cell sorter). Caspase-3 activity was determined by DEVD-afc-cleavage assay. Expression of ubiquitinated caspase-3 and cIAP-2 protein was detected by Western blot analysis and cIAP-2 mRNA by reverse transcriptase-polymerase chain reaction. RESULTS: Within 2 hours LPS induced cIAP-2 mRNA and protein. In addition, LPS increased ubiquitination of activated caspase-3. LPS significantly (p < 0.05) reduced spontaneous (66.1 +/- 2.3% to 24.8 +/- 4.8%) and CD95-induced (90.8 +/- 0.9% to 64.3 +/- 4.2%) apoptosis and caspase-3 activation. Inhibition of the proteasome completely abolished the antiapoptotic effect of LPS on spontaneous (52.6 +/- 2.4%) and CD95-induced (88.7 +/- 2.6%) apoptosis and degradation of caspase-3. CONCLUSIONS: Induction of cIAP-2 by endotoxins and accelerated degradation of activated caspase-3 by the proteasome might be responsible for reduced apoptosis in PMN during sepsis.

Mcl-1 correlates with reduced apoptosis in neutrophils from patients with sepsis.

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 x 10(6)/mL) from septic patients (n = 16) or healthy volunteers (n = 10) were incubated with either lipopolysaccharide (1 microg/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 regulation of apoptosis during sepsis; Bax remains unchanged.

Emergency stent-graft placement for hemorrhage control in acute thoracic aortic rupture.

OBJECTIVE: To report mid-term results of stent-graft (SG) implantation in acute thoracic aortic rupture as alternative to conventional open surgery with its associated high morbidity and mortality rates. METHODS: Out of a series of 69 patients undergoing thoracic aortic SG implantation since 1998, 24 (mean age 57+/-19 years, range 20-85-years-old) patients were treated on an emergency basis for hemorrhage control. The indication for SG placement was acute traumatic aortic rupture in 15 patients, type B dissection with contained rupture in 3 patients, penetrating aortic ulcer with periaortic hematoma in 3 patients, and thoracic aortic aneurysm rupture in 3 patients. Preoperative assessment was done by computed tomography (CT) scanning and echography. Patients were treated in the angiography suite by implantation of Excluder (n = 18) Talent (n = 4) Corvita (n = 1) and Vanguard (n = 1) self-expanding grafts. Local anesthesia was the most frequently used anaesthesiologic technique. RESULTS: Technical success rate of SG deployment was 100%. The early postoperative mortality was 12.5% (3 of 24). One patient suffered temporary paraplegia (4%). There was no intervention-related mortality during the mean follow-up of 34.1 months. Two secondary endoleaks were successfully treated with additional SG placement at 2 and 12 months postoperative, respectively. CONCLUSIONS: Emergency SG repair to control hemorrhage in patients with an acute thoracic aortic rupture is a less-invasive attractive and rational treatment option, especially if associated lesions or co-morbidity may interfere with the surgical outcome. Long-term follow-up results will be helpful to clarify procedure durability bounded by material failure and postoperative aneurysm or aortic wall remodelling.

The impact of body mass index on the development of systemic inflammatory response syndrome and sepsis in patients with polytrauma.

PURPOSE: Obesity is a growing problem in industrial nations. Our aim was to examine how overweight patients coped with systemic inflammatory response syndrome (SIRS) after polytrauma. METHODS: A total of 651 patients were included in this retrospective study, with an ISS ≥ 16 and age ≥ 16 years. The sample was subdivided into three groups: body mass index (BMI; all in kg/m(2))<25, BMI 25-30 and BMI>30, or low, intermediate and high BMI. The SIRS score was measured over 31 days after admission together with measurements of C-reactive protein (CRP), interleukin-6 (IL-6) and procalcitonin (PCT). Data are given as the mean ± SEM if not otherwise indicated. Kruskal-Wallis and χ(2) tests were used for statistical analysis and the significance level was set at p<.05. RESULTS: The maximum SIRS score was reached in the low BMI-group at 3.4 ± 0.4, vs. 2.3 ± 0.1 and 2.5 ± 0.2 in the intermediate BMI-group and high BMI-group, respectively (p<.0001). However, the maximum SIRS score was reached earlier in the BMI 25-30 group at 1.8 ± 0.2 days, vs. 3.4 ± 0.4 and 2.5 ± 0.2 days in the BMI<25 and BMI>30 groups, respectively (p<.0001). The incidence of sepsis was significantly higher in the low BMI group at 46.1%, vs. 0.2% and 0% in the BMI 25-30 and BMI>30 groups, respectively (p<.0001). No significant differences in the CRP, IL-6 or PCT levels were found between groups. CONCLUSIONS: A higher BMI seemed to be protective for these patients with polytrauma-associated inflammatory problems.