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.

There is increasing evidence that complement may play a role in bone development. Our previous studies demonstrated that the key complement receptor C5aR was strongly expressed in the fracture callus not only by immune cells but also by bone cells and chondroblasts, indicating a function in bone repair. To further elucidate the role of complement in bone healing, this study investigated fracture healing in mice in the absence of the key complement molecules C3 and C5. C3^-/- and C5^-/- as well as the corresponding wildtype mice received a standardized femur osteotomy, which was stabilized using an external fixator. Fracture healing was investigated after 7 and 21 days using histological, micro-computed tomography and biomechanical measurements. In the early phase of fracture healing, reduced callus area (C3^-/-: -25%, p=0.02; C5^-/-: -20% p=0.052) and newly formed bone (C3^-/-: -38%, p=0.01; C5^-/-: -52%, p=0.009) was found in both C3- and C5-deficient mice. After 21 days, healing was successful in the absence of C3, whereas in C5-deficient mice fracture repair was significantly reduced, which was confirmed by a reduced bending stiffness (-45%; p=0.029) and a smaller callus volume (-17%; p=0.039). We further demonstrated that C5a was activated in C3^-/- mice, suggesting cleavage via extrinsic pathways. Our results suggest that the activation of the terminal complement cascade in particular may be crucial for successful fracture healing.

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.

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.

Background: Various risk factors affecting outcome of elderly patients after proximal femur fracture have been identified. The present study aims to evaluate the impact of the fracture pattern in trochanteric fractures on postoperative mobility and complications. Methods: Ninety-two patients with a mean age of 84 years were included. According to the revised AO/OTA classification, fractures were divided into stable (AO 31A1) and unstable (AO 31A2/3) patterns. A follow-up examination was performed 12 months after cephalomedullary fixation to assess outcome parameters for mobility/activities of daily living (Parker Mobility Score (PMS)/Barthel Index (BI)) and complications (increase in requirement of care, hospital readmission, mortality rate). Results: At follow-up, patients with unstable trochanteric fracture patterns presented with lower PMS and BI compared to stable fractures (p < 0.05). Further, higher requirement of care and higher readmission rates compared to stable patterns were observed. Conclusion: Unstable trochanteric fractures presented inferior outcome compared to simple fracture patterns. This might be explained by the increasing surgical trauma in unstable fractures as well as by the mechanical impact of the lesser trochanter, which provides medial femoral support and is of functional relevance. Subsequent studies should assess if treatment strategies adapted to the specific fracture pattern (refixation of lesser trochanter) influence outcome in unstable trochanteric fractures.

Introduction: Little is known about the distribution of injuries in competitive snowboarding and there are no reports describing long-term complications of professional snowboarding. To examine the injury distribution and long-term impairments in active and retired professional snowboarders, a retrospective data analysis was performed using a questionnaire. As a control group, injuries of recreational snowboarders of a southern German university clinic were examined. Methods: Retired and active snowboarders were identified from the result lists of the International Ski Federation (FIS) and from the current team lists of the German-speaking European national snowboard teams. After identification, a questionnaire regarding injury distribution/treatment was sent to the athletes and the filled-in questionnaires were subsequently evaluated. Injuries in recreational snowboarding were evaluated by analyzing the medical records and surgical reports for a seven-year period. Results: Compared to the available literature, significantly more severe injuries that necessitated surgical treatment in recreational snowboarders were documented. Most injuries accounted for wrist fractures but also many nonunions and spinal fractures were recorded. Between active professionals, distinct differences in injury distribution were found. The number of days off differed greatly with less days in speed disciplines (35.5 days) and the maximum number of days off in snowboardcross (51 days). Injury distribution varied clearly with more injuries of the upper extremity and ankle in speed disciplines compared to snowboardcross and freestyle professionals, who exhibited more injuries to the lower extremity and head. Freestyle athletes used significantly less protectors compared to speed (P=0.01) and snowboardcross athletes (P=0.00). An analysis of retired professionals revealed a higher number of impairments in daily life and a significantly higher number of days off snowboarding (P=0.018). Conclusion: Knowledge about snowboard-specific injuries is a requirement for an appropriate treatment of these patients. This first description of long-term impairments after professional snowboarding highlights the importance of the development of specific strategies to prevent daily life impairments after a professional sports career.