Marcus Maier

Serum procalcitonin levels in patients with multiple injuries including visceral trauma.

Procalcitonin (PCT) is known to be a reliable biomarker of sepsis and infection. Elevation of serum or plasma PCT has also been observed after major surgery or trauma. The association of PCT with the severity or location of injury in multiple traumatized (polytrauma) patients has not been clearly established, to date. The aim of this study was therefore to evaluate the sensitivity of PCT as a biomarker for the diagnosis of abdominal trauma. In a prospective clinical study, PCT, interrleukin-6, and C-reactive protein were measured in blood (serum) samples obtained in the emergency room (D0) from 74 patients with multiple injuries and in serum samples obtained on the 2 days after trauma (D1, D2). PCT significantly increased during the first two posttraumatic days in patients with severe multiple injuries (n = 24, day 1: 3.37 ng/mL +/- 0.92 ng/mL; day 2: 3.27 ng/mL +/-0.97 ng/mL) as compared with patients with identical Injury Severity Score but without abdominal injury (day 1: 0.6 ng/mL +/- 0.18 ng/mL; 0.61 ng/mL +/- 0.21 ng/mL). Interrleukin-6 and C-reactive protein serum levels were not able to discriminate between patients with and without abdominal injury during the 2-day posttrauma observation period. In a specific evaluation of the abdominal injury pattern, a significant increase of serum PCT concentrations was observed on day 1 after trauma of the liver (4.04 ng/mL +/- 0.99 ng/mL) and the gut (4.63 ng/mL +/- 1.12 ng/mL) compared with other abdominal lesions (0.62 ng/mL +/- 0.2 ng/mL). Markedly elevated PCT concentrations were also evident after severe multiple injuries, including the liver/spleen in combination with thorax trauma (9.37 ng/mL +/- 2.71 ng/mL). Assessment of serum PCT seems to be significantly increased after abdominal trauma in severe multiple traumatized patients and may serve as a useful biomarker to support other diagnostic methods including ultrasound and CT scan. Although elevated levels of PCT during the first 2 days after trauma are more likely to be indicative of traumatic impact than of an ongoing status of sepsis, multiple events such as surgery, massive transfusion, and intensive care therapy might influence the PCT concentration.

Influence of pentoxifylline and albifylline on liver microcirculation and leukocyte adhesion after hemorrhagic shock in the rat.

The aim of this study was to evaluate the effects of two xanthine derivates, pentoxifylline (PTX) and its more metabolically stable analogue, albifylline (HWA 138), on hepatic sinusoidal perfusion and leukocyte endothelial interactions in the liver after hemorrhagic shock. Sprague-Dawley rats (n = 8 per group) were exposed to hemorrhagic shock at 40 mm Hg for 60 minutes and subsequently resuscitated with 60% of shed blood and lactated Ringers solution before intravital microscopy of the liver 3 hours after resuscitation. Using fluorescence markers, quantitative evaluations of red blood cell (RBC) and white blood cell (WBC) velocities and WBC endothelium interactions were performed. Animals were chosen randomly and blindly to receive either PTX or HWA 138 in a dosage of 25 mg/kg body weight 1 minute before resuscitation, or they received placebo. This was followed by a further infusion of 25 mg/kg body weight during the 3-hour resuscitation period. Although systemic parameters were comparable in all groups, both xanthine derivates enhanced the reduced velocity of RBCs and WBCs of the placebo group. Pathological values of WBC endothelium adhesion in the placebo group (adhesion index: 126.7 +/- 19.5 s/100 WBCs, mean +/- SE) was significantly reduced by PTX (64.4 +/- 10.5, p < 0.05) and HWA 138 (71.9 +/- 10.7, p < 0.05). The results indicate a significant reduction of shock-induced leukocyte adhesions to the sinusoidal endothelium in the liver. In addition, both xanthine derivates led to improved microvascular blood flow in the liver. Thus, PTX and HWA 138 reveal multiple positive effects on early shock-induced alterations in the liver, supporting earlier studies which indicated their potential application in shock therapy.

Functional outcome and complications following PHILOS plate fixation in proximal humeral fractures

OBJECTIVES Proximal humeral fractures account for approximately 5% of all fractures. New plating techniques have been developed to improve stability. The purpose of this study was to evaluate functional outcome following plate fixation with the Proximal Humeral Internal Locking System (PHILOS) and to analyze potential implant-related complications. METHODS The PHILOS plate was used for internal fixation of displaced proximal humeral fractures in 28 patients (20 females, 8 males; mean age 60.7+/-12.9 years). Fractures were caused by low-energy trauma (fall from standing height) in 21 patients, and by an accident while skiing or cycling in seven patients. Involvement was on the right in 16 cases and on the left in 12 cases. According to the Neer classification, 8, 12, and 8 patients had displaced 2-, 3-, or 4-part fractures, respectively. All patients received a similar physical therapy program following internal fixation with the PHILOS plate. The patients were assessed clinically and radiographically after a mean follow-up of 25.2+/-11.8 months. Functional outcome was assessed using the Constant-Murley score adjusted for age and gender. Range of motion and shoulder abduction strength were measured. The patients were also evaluated with the Disabilities of the Arm, Shoulder, and Hand (DASH) questionnaire and a visual analog scale (VAS). Complications during the follow-up period were recorded. RESULTS Twenty fractures (71.4%) healed in good anatomical position. At the end of the follow-up period, the mean Constant-Murley score was 57.9+/-21.7, and the mean age- and gender-adjusted Constant-Murley score was 67.5+/-23.6. The results were excellent or good in 16 patients (57.1%), moderate in one patient (3.6%), and poor in 11 patients (39.3%). The mean DASH and VAS scores were 28.3+/-24.3 and 75.4+/-21.2, respectively. Eleven complications (39.3%) were seen during the follow-up period. Reoperation was required in eight patients (72.3%). Complications included avascular necrosis of the humeral head in two patients (7.2%), subacromial impingement in six patients (21.4%), loosening of a locking head screw in one patient (3.6%), and transiently decreased radial nerve sensation in two patients (7.2%). Subacromial impingement was mainly caused by the superior plate position. CONCLUSION Our results demonstrate that the PHILOS plate provides sufficient fracture stabilization in the treatment of proximal humeral fractures of elderly patients.

Attenuation of leukocyte adhesion by recombinant TNF-binding protein after hemorrhagic shock in the rat.

Ischemia/reperfusion injury involves a large number of humoral and cellular mediators that activate leukocytes that subsequently migrate to local tissues. Tumor necrosis factor (TNF)-&agr; may be one of the most important mediators of this post-shock inflammatory response. In this study, we investigated the influence of a recombinant Type I (55 kDa) TNF-binding protein (TNF-BP) on leukocyte-endothelial interactions in the liver after hemorrhagic shock. Hemorrhagic shock was induced in female Sprague-Dawley rats (40 mmHg for 90 min) and a standardized resuscitation regimen was applied. At the time of resuscitation, animals were treated intravenously with either TNF-BP 4 mg/kg or placebo. The liver microcirculation was investigated using intravital fluorescence microscopy and immunohistochemistry at 5 h and 48 h after reperfusion. At 5 h, treatment with TNF-BP significantly reduced temporary leukocyte adhesion in the liver sinusoids as well as mean adhesion time of leukocytes in the hepatic central vein. In contrast, after 48 h, permanent leukocyte adhesion in the central hepatic vein was significantly reduced in the group receiving TNF-BP, whereas temporary leukocyte adhesion and mean adhesion time did not differ between the two groups. Both types of leukocyte adhesion, rolling adhesion after 5 h and firm adhesion after 48 h, were reduced in the group treated with TNF-BP, thereby suggesting a long-lasting anti-inflammatory effect.

Altered gene expression patterns in dendritic cells after severe trauma: implications for systemic inflammation and organ injury.

Dendritic cells (DCs) are professional antigen-presenting cells and members of the adoptive immunity. In addition, they play an important role in innate immunity within the systemic inflammatory response to trauma and sepsis. In this study, gene expression patterns of DC in patients with multiple trauma were studied. Total RNA was isolated from highly purified DCs (purity >95%) that were enriched from peripheral blood mononuclear cells and whole blood, respectively. Samples were obtained from 10 multiple trauma patients (injury severity score, 35.4 ± 10.6 on day of admission) and 5 healthy volunteers (control). Aliquots of target cDNAs and reference samples (cDNA derived from the monocytic cell line SIGM5) were cohybridized on a thematic medium-density microarray assessing 780 inflammation-related transcripts. Twenty transcripts were up-regulated in DCs of multiple trauma patients compared with healthy volunteers, whereas these differences were missed when RNA from whole blood was subjected to transcriptomic profiling. This cluster included central effector molecules of DC such as transcripts encoding for 5-lipoxygenase and the corresponding leukotriene 4 receptor, which regulate DC migration, adoptive immune responses, and airway inflammation, as well as CD74, CXCL4, or platelet factor 4, a chemokine not implicated as a product of DCs to date. In addition, genes involved in antiapoptosis (BCL2), intracellular signal transduction (mitogen-activated protein kinase), and secretion of mediators (VAMP2) were found to be up-regulated. The up-regulated transcripts suggest that life span and signaling function of DCs are altered by trauma. Furthermore, these data confirm and expand the central role of chemokines and lipid mediators as effector molecules of DC-mediated immune responses in systemic inflammation associated with severe trauma.ABBREVIATIONS-DC-dendritic cell; HV-healthy volunteer; ISS-injury severity score; MDC-myeloid dendritic cell; PDC-plasmacytoid dendritic cell; PT-polytrauma; VAMP-vesicle-associated membrane protein; WB-whole blood

Platelet Factor 4 Is Highly Upregulated in Dendritic Cells after Severe Trauma

Dendritic cells (DCs) represent an important linkage between the innate and adaptive immune system and express proinflammatory transcriptomic products early after trauma. The use of a genomic approach recently revealed that platelet factor 4 (PF4) is significantly upregulated in DCs in patients after multiple trauma. However, knowledge about subsequent PF4 alteration and its potential clinical relevance in the context of multiple trauma is still limited. We used quantitative reverse transcription-polymerase chain reaction to analyze PF4 expression in both myeloid DCs (MDCs) and plasmocytoid DCs (PDCs) isolated from 10 patients after multiple trauma. Intracellular PF4 as well as HLA-DR expression were detected by flow cytometry Furthermore, DCs and peripheral blood mononuclear cells were incubated on a monolayer of human umbilical endothelial cells and their adhesion properties were analyzed. The ratio of the DC subtypes (MDC and PDC) was assessed by flow cytometry. PF4 expression significantly increased on d 1 and d 2 as measured by reverse transcription-polymerase chain reaction. Intracellular PF4 content in MDCs and PDCs was significantly elevated in trauma patients compared with healthy controls. In addition, the surface antigen HLA-DR on MDCs was significantly elevated on d 1 and d 4 after trauma in patients compared with controls. However, cell adhesion of DCs did not show any significant differences between patients and controls. PF4 concentration in MDCs and PDCs significantly correlated with the injury severity score. These results confirm an early and subsequent posttraumatic activation of PF4 in DCs. PF4 also participates in the posttraumatic activation of DCs in relation to injury severity, a role that might be preferably based on the modification of receptor expression, whereas adhesion properties are largely unaffected.

Ausheilungsergebnisse konservativ und operativ versorgter kindlicher Femurfrakturen

ZusammenfassungDie klinischen und radiologischen Ausheilungsergebnisse kindlicher Femurschaftfrakturen sollten überprüft und die Therapiemöglichkeiten verglichen werden.101 Kinder im Alter von 5±0,4 Jahren wurden wegen einer Femurschaftfraktur von 1990–1999 stationär behandelt.Die Versorgung erfolgte bei 38% der Frakturen konservativ mit Overhead-Extension und Becken-Bein-Gips (mittleres Alter 2,2±0,5 Jahre), bei 32% mit Fixateur externe (6±0,5 Jahre), bei 17% mit ESIN (5,6±0,8 Jahre) und bei 12% mit anderen Osteosytheseverfahren.Der stationäre Aufenthalt war bei konservativer Behandlung (18±1,6 Tage) signifikant länger als bei der Behandlung mit Fixateur externe (12±1,2 Tage) und ESIN (8±0,9 Tage). Die radiologische Verlaufskontrolle zeigte eine signifikant bessere primäre Reposition durch die operativen Verfahren mit Fixateur externe und ESIN verglichen mit der konservativen Therapie.Komplikationen wie sekundäre Dislokation oder Infektion traten in 25% der mit Fixateur externe, in 6% der mit ESIN und in 10% der konservativ behandelten Fälle auf. Spätfolgen wie belastungsabhängige Schmerzen oder Kelloidbildung wurden bei 4% in der konservativ, bei 19% der mit Fixateur externe, jedoch bei keinem Patienten der mit ESIN behandelten Gruppe beobachtet.Zur Versorgung der Femurschaftfraktur im Kindesalter sind bei entsprechend zielgerichteter Indikationsstellung alle untersuchten Methoden geeignet.Bei eingeschränkter Reposition bleibt die konservative Therapie trotz zufriedenstellendem klinischem Ergebnis den jüngeren Patienten (<4 Jahre) mit entsprechend ausreichender Spontankorrektur vorbehalten. Die operative Versorgung mittels ESIN-Nagelung ist komplikationsarm und zeigt das beste Langzeitergebnis.Die Versorgung mit Fixateur externe ist sinnvoll, wenn die ESIN-Nagelung aufgrund der Frakturform (z.B.Mehrfragmentfrakturen), lokaler Weichteilverletzungen oder Zusatzverletzungen nicht durchführbar ist.AbstractThe clinical and radiological results of femoral shaft fractures in childhood were evaluated and compared in relation to different treatment modalities.One hundred and one children (mean age 5±0,4 years) were treated between 1990 to 1999. 38% of the patients were treated conservatively (mean age 2,2±0,5 years), 32% of the patients (mean age 6±0,5 years) were treated by external fixation,17% were treated with elastic stable intramedullary nailing (ESIN, mean age 5,6±0,8 years) and 12% underwent other internal fixation procedures.The duration of hospital stay was significantly longer in the conservative treatment group (18±1,6 days) than in the external fixator (12±1,2 days) as well as in the ESIN group (8±0,9 days).Radiological controls revealed a significantly better reduction of the fracture by operative procedures (external fixator,ESIN) as compared to conservative management. Complications,i.e.secondary dislocation or infection, occurred in 25% of patients in the external fixator group,6% of the ESIN patients, and in 10% of the conservatively treated patients. Late complications,i.e.weight bearing dependant pain or hypertrophic scaring,were developed in both the conservative treatment group (4%) and in the external fixator group (19%);however,no late complications were seen in the ESIN group.While each method examined is known to be suitable for treatment of femoral shaft fractures in childhood,each has defined indications. Also there is a limited possibility of fracture reduction in conservative treatment this method is indicated in younger children (<4 years) where spontaneous bone remodelling is likely.For older children the ESIN method showed a low rate of complications and demonstrates the best long term results.When ESIN is not possible because of local soft tissue damage,additional injuries,or in complex fractures, the external fixator proved to be an alternative treatment for femoral shaft fractures.

Suppression and Recovery of LPS-Stimulated Monocyte Activity After Trauma is Correlated With Increasing Injury Severity: A Prospective Clinical Study

BACKGROUND Monocytes represent a key immunocompetent cell type, whose functional capacity is profoundly influenced by systemic trauma. Because data on monocyte function in a heterogeneous trauma population, including slightly injured patients, is limited, we evaluated whether the magnitude of monocyte dysfunction can be related with injury severity and is useful as a predictive biomarker for development of systemic inflammatory response syndrome (SIRS) and sepsis. METHODS Blood samples were obtained from 58 patients at admission to a level 1 Trauma Unit (mean injury severity score [ISS] of 25.7; range 4-75), and daily for five successive days. Monocyte activity was assessed by measuring lipopolysaccharide (LPS)-stimulated interleukin (IL)-1-beta production. Levels of IL-6, IL-10, and procalcitonin were also determined and values were correlated to injury severity and occurrence of SIRS. RESULTS Even mildly injured individuals (ISS 1-8) showed a significant suppression of the LPS-response directly upon admission (p < 0.05). Both LPS-response (p = 0.049) and IL-6 levels (p = 0.046) were found to be predictive for the presence/diagnosis of SIRS. After minor trauma (ISS 1-8), the LPS-response returned to normal levels by day 2, whereas in more severely injured patients (ISS > or = 25) the suppression of monocyte activity persisted for the duration of the study period. CONCLUSION The extent of suppression of monocyte function is directly associated with the severity of trauma in both severely injured and patients with minor trauma. Acute posttraumatic changes in monocyte function and IL-6 concentrations were both predictive for the development of SIRS/sepsis. Although monocyte function in mildly injured patients is restored shortly after injury, the observed delay in recovery in severely traumatized patients may critically influence the clinical course.

Role of lung contusions on posttraumatic inflammatory response and organ dysfunction in traumatized patients

Background:Multiple trauma is often accompanied by lung contusion leading to secondary pulmonary inflammation and organ dysfunction. The particular role of lung contusions on the systemic inflammatory response remains unclear. Therefore, the aim of the present study was to compare the degree of lung contusion with markers of inflammation and multiple organ failure (MOF) in trauma patients.Methods:According to the Injury Severity Score (ISS), 45 patients were assigned to a low (< 25 points) and a high ISS group (> 25 points), respectively. Both groups were subdivided into minor and major lung injury groups as defined by computed tomography (CT) scan. Plasma levels of interleukin 6 (IL-6), interleukin 8 (IL-8), tumor necrosis factor (TNF) receptors, C-reactive protein (CRP), and polymorphonuclear (PMN) elastase were assessed, as well as the Murray lung score (MLS) and the MOF score.Results:Patients with low ISS present moderate activation of inflammation which is not influenced by the degree of lung contusion. In contrast, patients with a high ISS develop significant posttraumatic inflammation and MOF. Patients with high ISS and severe lung contusions present significantly higher MLS and MOF scores. Interestingly, patients of the high ISS group without severe lung contusions develop a similar degree of MLS and MOF only after 5 days following the traumatic insult. However, the initial plasma levels of IL-6 and IL-8 differ significantly in this group.Conclusion:Our data show that severe lung contusions contributes to an immediate onset of posttraumatic inflammation in severely traumatized patients, resulting in MOF, while in severely injured patients without lung contusion, this development requires up to 5 days.

Die elastisch-stabile Marknagelung der Femurfraktur beim Kind

ZusammenfassungOperationszielDie elastisch-stabile Markraumschienung (ESIN) ermöglicht mit minimalinvasiven Zugängen und in Abhängigkeit vom Frakturtyp eine übungsstabile Versorgung im Kindesalter.IndikationenESIN wird vor allem bei Femurschaftquer- und -schrägfrakturen (32-D/4.1 und 32-D/5.1) ab dem 4. Lebensjahr bis zum Schluss der Wachstumsfugen empfohlen.KontraindikationenHöhergradig offene Frakturen sowie knöcherne Trümmerzonen stellen eine Kontraindikation für die ESIN dar und sollten alternativ mit dem Fixateur externe versorgt werden.OperationstechnikNach Stichinzisionen medial und lateral suprakondylär werden die elastischen Markraumnägel nach Eröffnung der Kortikalis unmittelbar proximal der distalen Epiphysen fuge eingebracht und nach retrograd bis in die Trochanterregion vorgeschoben. In seltenen Fällen bei Frakturen im distalen Drittel werden die Markraumnägel ipsilateral proximal eingebracht und antegrad über die Fraktur geschoben. Biomechanisch ist auf eine Verklemmung der Nägel im Sinne einer stabilen Drei-Punkt-Abstützung zu achten.WeiterbehandlungMobilisierung unter Teilbelastung in Abhängigkeit vom Frakturtyp und von der Implantatlage. Während Querfrakturen mit guter Drei-Punkt-Abstützung der intramedullären Implantate eine zügige Aufbelastung erlauben, sind Mehrfragmentfrakturen nach ESIN über mehrere Wochen in der Belastbarkeit eingeschränkt.ErgebnisseDie minimalinvasive Methode erfährt große Akzeptanz von Seiten der Patienten und stellt bei guten bis sehr guten klinischen Ergebnissen die Methode der Wahl bei Femurschaftquer- und -schrägfrakturen (32-D/4.1 und 32-D/5.1) dar. Mehrfragmentfrakturen (32-D/5.2) sowie Frakturen im metaphysären Bereich (31-M/3.1 und 33-M/3.1) können bei der Versorgung mit ESIN Probleme bereiten und alternativ mit einem Fixateur externe behandelt werden.AbstractObjectiveElastic stable intramedullary nailing (ESIN) is a minimally invasive osteosynthesis technique that allows sufficient stabilization of fractures in children.IndicationsThe stabilization of femur fractures with ESIN is recommended for diapyseal femur fractures in children ≥ 4 years until closure of the growth plates.ContraindicationsOpen fractures with significant injuries to the soft tissues as well as burst fractures should not be treated with ESIN.Surgical TechniqueSmall incisions are made medial and lateral of the femur just above the distal growth plate. The cortex is perforated with an awl. The first ESIN is pushed via this perforation intramedullary retrograde via the fracture site to the proximal femur near the trochanteric region. Afterwards, the second nail is passed through the opposite cortex of the distal femur after opening it in the same way. The second nail has to be pushed parallel retrograde via the fracture site into the contralateral trochanteric region. The flexible nail design enables the surgeon to fix the fracture via a three-point stabilization.Postoperative ManagementPostoperative mobilization is allowed on crutches with reduced weight depending on the type of fracture. According to the ESIN position transverse fractures allow an early switch toward full weight bearing, whereas in fractures with multiple fragments, weight bearing should be reduced for several weeks until radiologic healing is seen.ResultsThe minimally invasive method of ESIN is a well-accepted treatment option for femur fracture in children yielding good and excellent clinical results. It is the treatment of first choice for transverse and oblique femoral fractures (32-D/4.1 und 32-D/5.1). Fractures with several fragments (32-D/5.2) as well as fractures of the metaphyseal region (31-M/3.1 und 33-M/3.1) may be difficult to stabilize with ESIN and might alternatively be treated with an external fixator.OBJECTIVE Elastic stable intramedullary nailing (ESIN) is a minimally invasive osteosynthesis technique that allows sufficient stabilization of fractures in children. INDICATIONS The stabilization of femur fractures with ESIN is recommended for diapyseal femur fractures in children > or = 4 years until closure of the growth plates. CONTRAINDICATIONS Open fractures with significant injuries to the soft tissues as well as burst fractures should not be treated with ESIN. SURGICAL TECHNIQUE Small incisions are made medial and lateral of the femur just above the distal growth plate. The cortex is perforated with an awl. The first ESIN is pushed via this perforation intramedullary retrograde via the fracture site to the proximal femur near the trochanteric region. Afterwards, the second nail is passed through the opposite cortex of the distal femur after opening it in the same way. The second nail has to be pushed parallel retrograde via the fracture site into the contralateral trochanteric region. The flexible nail design enables the surgeon to fix the fracture via a three-point stabilization. POSTOPERATIVE MANAGEMENT Postoperative mobilization is allowed on crutches with reduced weight depending on the type of fracture. According to the ESIN position transverse fractures allow an early switch toward full weight bearing, whereas in fractures with multiple fragments, weight bearing should be reduced for several weeks until radiologic healing is seen. RESULTS The minimally invasive method of ESIN is a well-accepted treatment option for femur fracture in children yielding good and excellent clinical results. It is the treatment of first choice for transverse and oblique femoral fractures (32-D/4.1 und 32-D/5.1). Fractures with several fragments (32-D/5.2) as well as fractures of the metaphyseal region (31-M/3.1 und 33-M/3.1) may be difficult to stabilize with ESIN and might alternatively be treated with an external fixator.