E-scooter accidents-epidemiology and injury patterns: 3-year results from a level 1 trauma center in Germany.

INTRODUCTION: Since the introduction of e-scooters in Germany in 2019, they are becoming more and more popular and associated injuries have increased significantly. The aim of this study was to assess the injury patterns after e-scooter accidents. MATERIALS AND METHODS: From May 2019 to October 2022, all consecutive patients who presented at our emergency department (ED) following e-scooter accidents were included in our study and retrospectively analyzed. RESULTS: A total of 271 patients were included in our study. The mean age was 33 years. 38% of the patients were female and 62% were male. Most common injuries were traumatic brain injuries in 38% of the patients together with fractures affecting the upper limb (17%). An operative treatment was necessary in 40 patients. Most of the patients presented at night and about 30% were under the influence of alcohol. CONCLUSIONS: Our study shows one of the largest cohort of patients suffering e-scooter accidents in Europe. Compulsory helmet use, stricter alcohol controls and locking periods could contribute significantly to safety.

High rate of complications after corrective midfoot/subtalar arthrodesis and Achilles tendon lengthening in Charcot arthropathy type Sanders 2 and 3.

PURPOSE: Corrective midfoot resection arthrodesis is the standard treatment of Charcot arthropathy type Sanders 2 and 3 with severe dislocation. In order to critically evaluate the effect of surgical correction, a retrospective analysis of our patient cohort was performed. Hereby, special emphasis was set on the analysis of the pre- and post-operative equinus position of the hindfoot. METHODS: Retrospectively, all patients (n = 82) after midfoot resection arthrodesis in Charcot type Sanders 2 or 3 were included. Complications were recorded, and the mean complication-free interval was calculated. Additionally, the calcaneal pitch as well as Meary's angle were measured pre- and post-operatively and in case of complications. RESULTS: Overall complication rate was 89%. Revision surgery was necessary in 46% of all patients. The mean complication-free interval was 285 days (0-1560 days). Calcaneal pitch and Meary's angle significantly improved after operation but returned to pre-operative values after onset of complications. Achilles tendon lengthening showed no significant effects on the mean complication-free interval. CONCLUSION: Operative treatment of Charcot arthropathy remains a surgical challenge with high complication rates. Surgical correction of equinus position has been highlighted for successful treatment but was not able to prevent complications in this study, which is demonstrated by the recurrent decrease of the calcaneal pitch in cases of reoperation. Therefore, as a conclusion of our results, our treatment algorithm changed towards primarily addressing the equinus malpositioning of the hindfoot by corrective arthrodesis of the hindfoot.

Biomechanical stability of short versus long proximal femoral nails in osteoporotic subtrochanteric A3 reverse-oblique femoral fractures: a cadaveric study.

PURPOSE: Due to the demographic change towards an older society, osteoporosis-related proximal femur fractures are steadily increasing. Intramedullary nail osteosyntheses are available in different lengths, where the field of application overlaps. The aim of this study was to investigate whether subtrochanteric fractures can also be treated stably using a short femoral intramedullary nail in cadaveric bones. METHODS: A short PFNA and a long PFNA were implanted in both seven artificial bones and osteoporotic human specimens. A standardized AO 31-A3 (reverse-oblique) fracture was placed in the specimens with a lateral fracture spur 2 cm proximal to the distal locking screw (short PFNA) and embedded. The simulated iliotibial tract was preloaded to 50 N. The force was applied at 10 mm/min up to a force of 200-800 N (artificial bones) and 200-400 N (human specimens). The dislocation of the fracture gap, the axial bone stiffness of bone construct and the force curve of the tractus iliotibialis were measured. RESULTS: There is no difference in the use of a short versus long PFNA in terms of stiffness of the overall construct and only a slight increase in dislocation in the fracture gap results with short PFNA compared to a long intramedullary nail. CONCLUSION: In summary of the available literature, the present study supports the thesis that there is no clinical difference between long versus short nails in A3 femur fractures. Furthermore, the present study defines a safe biomechanical range of fracture extension above the locking screw of the short intramedullary nail. LEVEL OF EVIDENCE: III.

Jumper's fracture of the sacrum: a novel and reproducible way for successful reduction and fixation.

PURPOSE: Surgical treatment of jumper's fractures is a highly demanding situation for the surgeon due to its rareness and frequent association with severe concomitant injuries. There is no current consensus regarding a standard treatment approach, thus reducing quality of care. Our objectives were to describe, apply and assess a novel surgical technic. METHODS: The presented research is an observational retrospective study of patients who underwent the described novel surgical intervention in a level 1 trauma center. We conducted analyses of the patient cohort using patient-related outcome measures at least 1 year after surgery, as well as investigating pain, quality of life and the clinical effectiveness of the procedure. RESULTS: A total of 24 patients (17 male and 7 female) with an average age 47 ± 16.3 years were included. ISS scores ranged from 9 to 66 with a mean ISS of 40 ± 15. Clinical scores exist of 15 out of 24 patients (62.5%). The mean VAS score was 53.7 ± 12.9. The mean EQ-5D index was 0.68 ± 0.22. Significant negative correlation existed between the ISS value and the EQ-5D index (r = - 0.704; p < 0.005) and EQ-5D VAS (r = - 0.809; p < 0.001). Anatomical reduction was achieved in all patients (n = 24). Radiological follow-up was performed in 58%. CONCLUSION: We present one of the largest studies with operatively treated jumper's fractures of the sacrum. The technique is capable of reproducibly restoring the physiological anatomy of the patient and allows pain-adapted mobilization.

[Complications after intramedullary stabilization of clavicle fractures]. / Komplikationen nach intramedullärer Stabilisierung von Klavikulafrakturen.

BACKGROUND: Operative treatment of clavicle fractures by intramedullary nailing with titanium elastic nailing (TEN) has been established as an alternative to plate osteosynthesis for many years. The main complication after TEN osteosynthesis is nail migration. The goal of this study was evaluation of predictors for medial nail migration and comparison with plate osteosynthesis. MATERIAL AND METHODS: A retrospective analysis of electronic patient charts, surgical protocols and radiographs of all operatively treated clavicle shaft fractures between 2010-2014 (n = 141) was performed. When evaluating the patient charts and the surgical protocols special attention was paid to the fracture type, the duration of the operation, the need for an open reduction and the onset of complications as well as the duration until implant removal. Radiographs were analyzed concerning the implant location and an implant migration. RESULTS: Surgery time (39 vs. 83 min) as well as the time to implant removal (226 vs. 495 days) were significantly reduced (p = 0.00), while complication (39% vs. 21.4%) as well as reoperation rates (15% vs. 7.1%; p = 0.033) were increased in TEN compared to plate osteosynthesis. The main complication was medial nail migration. The following predictors regarding medial migration could be identified: open or closed reduction (p = 0.021), multifragmentary fractures (p = 0.049), oblique fractures (p = 0.08) and TEN thickness (33% at 2 mm, 0% at 3 mm). DISCUSSION: Advantages of TEN are a shorter surgery time as well as a shorter duration until implant removal. The TEN osteosynthesis led to a significantly increased complication rate, with nail migration representing the major reason. When predictors for medial TEN migration are considered, type B and C fractures can also be sufficiently treated by a large diameter TEN.

Early Detection of Junctional Adhesion Molecule-1 (JAM-1) in the Circulation after Experimental and Clinical Polytrauma.

Severe tissue trauma-induced systemic inflammation is often accompanied by evident or occult blood-organ barrier dysfunctions, frequently leading to multiple organ dysfunction. However, it is unknown whether specific barrier molecules are shed into the circulation early after trauma as potential indicators of an initial barrier dysfunction. The release of the barrier molecule junctional adhesion molecule-1 (JAM-1) was investigated in plasma of C57BL/6 mice 2 h after experimental mono- and polytrauma as well as in polytrauma patients (ISS ≥ 18) during a 10-day period. Correlation analyses were performed to indicate a linkage between JAM-1 plasma concentrations and organ failure. JAM-1 was systemically detected after experimental trauma in mice with blunt chest trauma as a driving force. Accordingly, JAM-1 was reduced in lung tissue after pulmonary contusion and JAM-1 plasma levels significantly correlated with increased protein levels in the bronchoalveolar lavage as a sign for alveolocapillary barrier dysfunction. Furthermore, JAM-1 was markedly released into the plasma of polytrauma patients as early as 4 h after the trauma insult and significantly correlated with severity of disease and organ dysfunction (APACHE II and SOFA score). The data support an early injury- and time-dependent appearance of the barrier molecule JAM-1 in the circulation indicative of a commencing trauma-induced barrier dysfunction.

Long bone uninfected non-union: grafting techniques.

Long bone non-unions represent a serious clinical and socioeconomical problem due to the prolonged episodes, frequent sequelae, and variable treatment effectiveness. Bone grafts, classically involving the autologous iliac crest graft as the 'gold standard' bone graft, enhance bone regeneration and fracture healing incorporating osteoconductive and/or osteoinductive/osteogenic capacity to the non-union under treatment. Structural alternatives to autologous bone grafts include allografts and bone substitutes, expanding the available stock but loosing biological properties associated with cells in the graft. Biological alternatives to autologous bone grafts include bone marrow concentration from iliac crest aspiration, bone marrow aspiration from reaming of the diaphyseal medullary canal in the long bones, and isolated, expanded mesenchymal stem cells under investigation. When the combination with natural and synthetic bone substitutes allows for larger volumes of structural grafts, the enhancement of the biological regenerative properties through the incorporation of cells and their secretoma permits to foresee new bone grafting solutions and techniques.

Quality of Life and Patient Satisfaction After the Provision of an Orthopedic Knee Scooter­a Multicenter Randomized Controlled Trial.

BACKGROUND: Partial or total avoidance of weight-bearing by a lower limb is regularly needed after trauma and surgery. There are approximately 200 such cases per 100 000 persons per year. Forearm crutches have mainly been used in Germany until now to keep these patients mobile. For those who lack the strength or coordination needed to use crutches, a wheelchair may become necessary, or they might find themselves forced to continue weight-bearing on the affected limb, with possible impending adverse consequences and complications. METHODS: The supplementary use of a new type of orthopedic scooter by patients who must avoid weight-bearing by a lower limb, wholly or in part, was studied in a multicenter randomized controlled trial involving 88 subjects. The endpoints were improvement in quality of life (EQ5D, SF36) and improved abilities in everyday life (retrospective registration: DRKS00032980). RESULTS: Patients who used orthopedic knee scooters (KS) reported a better overall state of health more frequently than those who used forearm crutches (UC) (SF-36 score: 67 [KS group], 95% CI [61; 73]; 59 [UC group], [53; 64]). They also reported less anxiety and depressed mood, greater mobility, and more independence than the patients who used crutches. In addition, they more frequently reported being able to transport themselves 4 x 500 meters in less than 20 minutes (n = 30 [KS], 63.8% [48.5; 77.3]; n = 6 [UC], 14.6% [5.6, 29.2]). CONCLUSION: The supplementary use of an orthopedic knee scooter can improve these patients' mobility and independence and prolong the distance over which they can transport themselves. For many patients, this form of treatment may well shorten the time of their total or partial inability to work and thus lower the socioeconomic costs of lower limb injuries and surgery.

Preventing Atrophic Long-Bone Nonunion: Retrospective Analysis at a Level I Trauma Center.

Background: Among the risk factors for nonunion are unchangeable patient factors such as the type of injury and comorbidities, and factors that can be influenced by the surgeon such as fracture treatment and the postoperative course. While there are numerous studies analyzing unchangeable factors, there is poor evidence for factors that can be affected by the physician. This raises the need to fill the existing knowledge gaps and lay the foundations for future prevention and in-depth treatment strategies. Therefore, the goal of this study was to illuminate knowledge about nonunion in general and uncover the possible reasons for their development; Methods: This was a retrospective analysis of 327 patients from 2015 to 2020 from a level I trauma center in Germany. Information about patient characteristics, comorbidities, alcohol and nicotine abuse, fracture classification, type of osteosynthesis, etc., was collected. Matched pair analysis was performed, and statistical testing performed specifically for atrophic long-bone nonunion; Results: The type of osteosynthesis significantly affected the development of nonunion, with plate osteosynthesis being a predictor for nonunion. The use of wire cerclage did not affect the development of nonunion, nor did the use of NSAIDs, smoking, alcohol, osteoporosis and BMI; Conclusion: Knowledge about predictors for nonunion and strategies to avoid them can benefit the medical care of patients, possibly preventing the development of nonunion.

Biomechanical comparison of screw vs. cerclage refixation in orthogeriatric lesser trochanteric fractures: a cadaveric study.

PURPOSE: Osteoporosis-related proximal femur fractures continue to increase significantly due to demographic change. This study was designed to evaluate the biomechanical stability of two different fixation methods (cerclage vs. screw) for refixation of a trochanter minor fragment in the pertrochanteric fractures in cadaveric bones. METHODS: Artificial bones (n = 14) and human bones (n = 16) were treated with a DHS and the trochanter minor fragment was reduced by cerclage wiring or direct screw fixation. After preloading the simulated iliopsoas with 10 N, a tensile test was performed, ending with either a 70% loss of strength or avulsion of the fragment. The mean values of the avulsion force and the surface strain were recorded. RESULTS: All tensile tests showed no significant differences between refixation using a direct screw or wire cerclage, for both artificial bones and human specimens. Absolute values showed higher avulsion forces after direct screw fixation than refixation with a wire cerclage. The surface tension of specimens treated with direct screw fixation was lower than that of specimens treated with wire cerclage. An opposite effect was seen in artificial bones. Both effects were not statistically significant. CONCLUSION: Based on the equal stability after lag screw placement compared to cerclage wiring, we promote the placement of a lag screw into the lesser trochanter fragment in pertrochanteric femur fractures when using a dynamic hip screw. LEVEL OF EVIDENCE: Level III.

Changing patterns in the epidemiology of tibial plateau fractures: a 10-year review at a level-I trauma center.

PURPOSE: Mobility patterns of western societies have been changing due to ongoing demographic change. Therefore, continuously updated epidemiological data on fracture morphology and treatment strategies are needed. METHODS: This retrospective single-center study included all tibial plateau fractures (TPF) between January 2011 and December 2020 in a level-I trauma center in Central Europe. Epidemiology, trauma mechanism and fracture morphology were analyzed. Age- and sex-specific differences regarding fracture classification (Schatzker, AO/OTA, Moore) and changes during the study period are highlighted. RESULTS: A total of 607 patients (55.2% women, 44.8% men, mean age 52.9 years (± 17.9)) were included in the study, 462 (76.1%) thereof having undergone surgical treatment. Over the decade, an increase in mean age (+ 7.4 years; p = 0.10), incidence (+ 68%; p < 0.05) and low-energy trauma was observed, with the highest peak in elderly women. Within classifications, AO/OTA 41-B3 (24.9%), Schatzker II (26.8%) and Moore V (46.6%) fractures were the most common. CONCLUSION: Incidence (+ 68%), mean age and fractures with signs of knee dislocation of tibial plateau fracture increased over the last decade and low-energy trauma mechanism are more frequent. As the increase in incidence is mainly seen in older women, the comorbidities and need for immediate postoperative full weight-bearing have to be considered in treatment strategies.

Micro-Structural and Biomechanical Evaluation of Bioresorbable and Conventional Bone Cements for Augmentation of the Proximal Femoral Nail.

Osteoporotic proximal femur fractures are on the rise due to demographic change. The most dominant surgical treatment option for per/subtrochanteric fractures is cephalomedullary nailing. As it has been shown to increase primary stability, cement augmentation has become increasingly popular in the treatment of osteoporotic per/subtrochanteric femur fractures. The ultimate goal is to achieve stable osteosynthesis, allowing for rapid full weight-bearing to reduce possible postoperative complications. In recent years, bioresorbable bone cements have been developed and are now mainly used to fill bone voids. The aim of this study was to evaluate the biomechanical stability as well as the micro-structural behaviour of bioresorbable bone cements compared to conventional polymethylmethacrylate (PMMA)-cements in a subtrochanteric femur fracture model. Biomechanical as well as micro-computed tomography morphology analysis revealed no significant differences in both bone cements, as they showed equal mechanical stability and tight interdigitation into the spongious bone of the femoral head. Given the positive risk/benefit ratio for bioresorbable bone cements, their utilisation should be evaluated in future clinical studies, making them a promising alternative to PMMA-bone cements.

Gluteal Muscle Fatty Atrophy: An Independent Risk Factor for Surgical Treatment in Elderly Patients Diagnosed with Type-III Fragility Fractures of the Pelvis.

BACKGROUND: Gluteal muscle fatty atrophy (gMFA) might impair pelvic stability and negatively influence remobilization in patients with fragility fractures of the pelvis (FFP). This study aimed to investigate the association between gMFA and surgical indication in patients with FFP. METHODS AND MATERIALS: A retrospective analysis of 429 patients (age ≥80) diagnosed with FFP was performed. gMFA of the gluteus maximus, medius, and minimus was evaluated using a standard scoring system based on computer tomography images. RESULTS: No significant difference was found in gMFA between genders or among FFP types. The severity of gMFA did not correlate with age. The severity of gMFA in the gluteus medius was significantly greater than in the gluteus maximus, whereas the most profound gMFA was found in the gluteus minimus. gMFA was significantly more severe in patients who underwent an operation than in conservatively treated patients with type-III FFP, and an independent correlation to surgical indication was found using logistic regression. CONCLUSION: Our findings imply that gMFA is an independent factor for surgical treatment in patients with type-III FFP. Besides focusing on the fracture pattern, the further evaluation of gMFA could be a feasible parameter for decision making toward either conservative or surgical treatment of type-III FFP.

Evidence-Based Surgical Treatment Algorithm for Unstable Syndesmotic Injuries.

BACKGROUND: Surgical treatment of unstable syndesmotic injuries is not trivial, and there are no generally accepted treatment guidelines. The most common controversies regarding surgical treatment are related to screw fixation versus dynamic fixation, the use of reduction clamps, open versus closed reduction, and the role of the posterior malleolus and of the anterior inferior tibiofibular ligament (AITFL). Our aim was to draw important conclusions from the pertinent literature concerning surgical treatment of unstable syndesmotic injuries, to transform these conclusions into surgical principles supported by the literature, and finally to fuse these principles into an evidence-based surgical treatment algorithm. METHODS: PubMed, Embase, Google Scholar, The Cochrane Database of Systematic Reviews, and the reference lists of systematic reviews of relevant studies dealing with the surgical treatment of unstable syndesmotic injuries were searched independently by two reviewers using specific terms and limits. Surgical principles supported by the literature were fused into an evidence-based surgical treatment algorithm. RESULTS: A total of 171 articles were included for further considerations. Among them, 47 articles concerned syndesmotic screw fixation and 41 flexible dynamic fixations of the syndesmosis. Twenty-five studies compared screw fixation with dynamic fixations, and seven out of these comparisons were randomized controlled trials. Nineteen articles addressed the posterior malleolus, 14 the role of the AITFL, and eight the use of reduction clamps. Anatomic reduction is crucial to prevent posttraumatic osteoarthritis. Therefore, flexible dynamic stabilization techniques should be preferred whenever possible. An unstable AITFL should be repaired and augmented, as it represents an important stabilizer of external rotation of the distal fibula. CONCLUSIONS: The current literature provides sufficient arguments for the development of an evidence-based surgical treatment algorithm for unstable syndesmotic injuries.

Peripelvic Morel-Lavallée lesion following high-energy spine trauma: Case report and review of treatment options.

The Morel-Lavallée lesion (MLL) is an internal degloving injury typically associated with high-energy trauma and is suspected to be underdiagnosed in a majority of cases. Here, we illustrate the typical clinical and radiological characteristics of an extensive peripelvic MLL in a 50-year-old patient presenting to our trauma outpatient clinic with peripelvic pain, bruising and swelling six weeks after severe spine trauma caused by a high-energy car accident. Using this case study as an example, current therapeutic approaches are discussed. Therapeutic decisions should be based on clinical symptoms, lesion size, severity, age and co-morbidities. Extensive, symptomatic and chronic lesions should be addressed with early débridement, irrigation and drainage in order to prevent complications like infection or soft tissue necrosis.

Geriatric patients with dementia show increased mortality and lack of functional recovery after hip fracture treated with hemiprosthesis.

PURPOSE: Operative timing, perioperative management and postoperative rehabilitation are rising challenges in orthopedic geriatric trauma. The aim of this study was to determine the outcome of patients with dementia or with a high number of comorbidities treated with hemiprosthesis after hip fracture. Literature regarding patients with high comorbidities is scarce, leaving nothing but endoprosthetic treatment for even the sickest, immobile patients. METHODS: A retrospective chart review of 326 patients (mean age 81 ± 9 years; 230 women and 96 men) with hip fractures treated between 2012 and 2017 with a hemiprosthesis was performed. Primary outcome measures were surgical and nonsurgical complication rates, best achievable mobilisation during the hospital stay and mortality. RESULTS: Patients with dementia had 20-fold increased risk to be bedridden after surgery and ninefold increased risk of dying (p < 0.005). Furthermore, they needed significantly more revision surgeries because of surgical complications. Patients classified ASA IV and V had significantly lower postoperative mobilization levels with only 10% able to walk with crutches and 53% bedridden. They also had significantly more non-surgical complications while dementia had no effect on non-surgical complication rate. CONCLUSION: Patients classified ASA IV and V or suffering dementia show poor outcome after hip fracture treated with hemiprosthesis. Multidisciplinary approaches including surgeons, geriatricians, physiotherapists and psychiatrists are needed to improve the outcome of these patients. Especially in a subgroup of patients, where no mobilization is expected, alternative treatment options may be considered.

Intraoperative alignment correlates well with long standing radiographs - The X-ray grid method in complex knee surgery.

OBJECTIVE: While long standing radiographs (LSR) represent the gold standard for preoperative alignment assessment and planning of lower limb deformity corrections, there is no consensus about the intraoperative alignment assesments (IAC) due to various limitations of the common methods. The present study introduces a radiolucent X-ray grid with integrated radiopaque lines explicitly designed for fluoroscopic IAC and evaluates its reliability in comparsion to the LSR. METHODS: Patients with posttaumatic and congenital lower limb deformity surgery and preoperative LSR as well as fluoroscopic IAC utilizing the X-ray grid were retrospectively included to the study. The mechanical axis deviation (MAD) in percentage of the maximum tibial width from the medial to the lateral in comparison between the image pairs was set as primary outcome parameter. Multiple rater and measurements determined intra- and interobserver reliabilit of both imaging methods. In addition, the effects of age, gender, body mass index (BMI), etiology, joint line convergence angle (JLCA), and extent varus or valgus deformity were analysed. RESULTS: A total of 84 patients were finally included. The mean absolute difference of MAD between the two techniques was 7.2 ± 0.8%. MAD between the LSR and IAC correlated at a high level (R = 0.96, p <0.001). The agreement decreased with increasing extent of deformity (p <0.01) and with higher deviation of JLCA between LSR and IAC (p <0.01). Intra- and interobserver concordance correlation coefficient (CCC) for MAD measurements were 0.99 for both imaging techniques. CONCLUSION: Fluoroscopy combined with the X-ray grid method is a valid tool for intraoperative assessment of lower limb alignment in deformity correction surgery, and the correlation between LSR and IAC is better than in other similar techniques described in the literature. However, in case of severe coronal alignment deformity and highly divergent JLCA, the agreement between both imaging techniques decreases significantly.

New insights of an old defense system: structure, function, and clinical relevance of the complement system.

The complement system was discovered a century ago as a potent defense cascade of innate immunity. After its first description, continuous experimental and clinical research was performed, and three canonical pathways of activation were established. Upon activation by traumatic or surgical tissue damage, complement reveals beneficial functions of pathogen and danger defense by sensing and clearing injured cells. However, the latest research efforts have provided a more distinct insight into the complement system and its clinical subsequences. Complement has been shown to play a significant role in the pathogenesis of various inflammatory processes such as sepsis, multiorgan dysfunction, ischemia/reperfusion, cardiovascular diseases and many others. The three well-known activation pathways of the complement system have been challenged by newer findings that demonstrate direct production of central complement effectors (for example, C5a) by serine proteases of the coagulation cascade. In particular, thrombin is capable of producing C5a, which not only plays a decisive role on pathogens and infected/damaged tissues, but also acts systemically. In the case of uncontrolled complement activation, "friendly fire" is generated, resulting in the destruction of healthy host tissue. Therefore, the traditional research that focuses on a mainly positive-acting cascade has now shifted to the negative effects and how tissue damage originated by the activation of the complement can be contained. In a translational approach including structure-function relations of this ancient defense system, this review provides new insights of complement-mediated clinical relevant diseases and the development of complement modulation strategies and current research aspects.

The anaphylatoxin receptor C5aR is present during fracture healing in rats and mediates osteoblast migration in vitro.

BACKGROUND: There is evidence that complement components regulate cytokine production in osteoblastic cells, induce cell migration in mesenchymal stem cells, and play a regulatory role in normal enchondral bone formation. We proved the hypothesis that complement might be involved in bone healing after fracture. METHODS: We investigated the expression of the key anaphylatoxin receptor C5aR during fracture healing in rats by immunostaining after 1, 3, 7, 14, and 28 days. C5aR expression was additionally analyzed in human mesenchymal stem cells (hMSC) during osteogenic differentiation, in human primary osteoblasts, and osteoclasts by reverse transcriptase polymerase chain reaction and immunostaining. Receptor functionality was proven by the migratory response of cells to C5a in a Boyden chamber. RESULTS: C5aR was expressed in a distinct spatial and temporal pattern in the fracture callus by differentiated osteoblast, chondroblast-like cells in cartilaginous regions, and osteoclasts. In vitro C5aR was expressed by osteoblasts, osteoclasts, and hMSC undergoing osteogenic differentiation. C5aR was barely expressed by undifferentiated hMSC but was significantly induced after osteogenic differentiation. C5aR activation by C5a induced strong chemotactic activity in osteoblasts, and in hMSC, which had undergone osteogenic differentiation, being abolished by a specific C5aR antagonist. In hMSC, C5a induced less migration reflecting their low level of C5aR expression. CONCLUSIONS: Our in vitro and in vivo results demonstrated the presence of C5aR in bone forming osteoblasts and bone resorbing osteoclasts. It is suggested that C5aR might play a regulatory role in fracture healing in intramembranous and in enchondral ossification, one possible function being the regulation of cell recruitment.

Complement Factor C5a Inhibits Apoptosis of Neutrophils-A Mechanism in Polytrauma?

Life-threatening polytrauma results in early activation of the complement and apoptotic system, as well as leukocytes, ultimately leading to the clearance of damaged cells. However, little is known about interactions between the complement and apoptotic systems in PMN (polymorphonuclear neutrophils) after multiple injuries. PMN from polytrauma patients and healthy volunteers were obtained and assessed for apoptotic events along the post-traumatic time course. In vitro studies simulated complement activation by the exposure of PMN to C3a or C5a and addressed both the intrinsic and extrinsic apoptotic pathway. Specific blockade of the C5a-receptor 1 (C5aR1) on PMN was evaluated for efficacy to reverse complement-driven alterations. PMN from polytrauma patients exhibited significantly reduced apoptotic rates up to 10 days post trauma compared to healthy controls. Polytrauma-induced resistance was associated with significantly reduced Fas-ligand (FasL) and Fas-receptor (FasR) on PMN and in contrast, significantly enhanced FasL and FasR in serum. Simulation of systemic complement activation revealed for C5a, but not for C3a, a dose-dependent abrogation of PMN apoptosis in both intrinsic and extrinsic pathways. Furthermore, specific blockade of the C5aR1 reversed C5a-induced PMN resistance to apoptosis. The data suggest an important regulatory and putative mechanistic and therapeutic role of the C5a/C5aR1 interaction on PMN apoptosis after polytrauma.