Mika Rollmann

Predictors of mortality for complex fractures of the pelvic ring in the elderly: a twelve-year review from a German level I trauma center.

STUDY OBJECTIVE To document mortality rate and predictors of mortality in elderly patients with complex pelvic fractures. METHODS We reviewed a total of 84 subjects whose ages were above 70 years with complex pelvic fractures, admitted to our hospital from January 2001 to December 2012. A multivariate linear regression model was used to determine the predictors of mortality in the study population. The median age of the patients was 80.4 years (range 70-94 years). 65 of 84 (77%) patients were females. There were 72 Tile Type B fractures (86%) and 12 Type C fractures (14%). The most common associated injuries were thoracic, extremity and head injuries, with incidence of 13 (15%), 11 (13%), and 9 (11%), respectively. RESULTS The mortality rate was 10% in our study population. The initial haemoglobin on admission (p<0.01), the presence of blood vessel injuries (p<0.01) and the number of PRBCs transfused within the first six hours after admission (p<0.01) independently predicted mortality in elderly patients with complex pelvic fractures. CONCLUSION Although there is a downward trend in mortality in elderly patients with complex pelvic fractures, haemodynamic instability still has a significant impact on survival of those patients.

Fracture healing redefined

It is well established that local mechanical conditions and interfragmentary movement are important factors for successful bone healing and may vary dramatically with patient fracture-load and activity. Up until now however it was technically impossible to use these key influence parameters in the aftercare treatment process of human lower extremity fractures. We propose a theory that with state of the art sensor technology these biomechanical influences can not only be monitored in vivo, but also used for individualized therapy protocols. Local measurement systems for fracture healing are available but remain research tools, due to various technical issues. To investigate the biomechanical influences on healing right away surrogate sensor tools are needed. Various gait characteristics have been proposed as surrogate measures. Currently available sensor tools could be modified with the appropriate support structure to allow such measurements continuously over the course of a fracture healing. Interdisciplinary work between clinicians, software engineers with computer and biomechanical simulations is needed. Through such a sensor system human boundary conditions for fracture healing could not only be defined for the first time, but also used for a unique, extendible aftercare system. With this tool critical healing situations would be detected much earlier and could be prevented with easy activity modifications, reducing patient and socioeconomic burden of disease. The hypothesis, necessary tools and support structures are presented.

Comparative Degradomics of Porcine and Human Wound Exudates Unravels Biomarker Candidates for Assessment of Wound Healing Progression in Trauma Patients

Impaired cutaneous wound healing is a major complication in elderly people and patients suffering from diabetes, the rate of which is rising in industrialized countries. Heterogeneity of clinical manifestations hampers effective molecular diagnostics and decisions for appropriate therapeutic regimens. Using a customized positional quantitative proteomics workflow, we have established a time-resolved proteome and N-terminome resource from wound exudates in a clinically relevant pig wound model that we exploited as a robust template to interpret a heterogeneous dataset from patients undergoing the same wound treatment. With zyxin, IQGA1, and HtrA1, this analysis and validation by targeted proteomics identified differential abundances and proteolytic processing of proteins of epidermal and dermal origin as prospective biomarker candidates for assessment of critical turning points in wound progression. Thus, we show the possibility of using a fine-tuned animal wound model to bridge the translational gap as a prerequisite for future extended clinical studies with large cohorts of individuals affected by healing impairments. Data are available via ProteomeXchange with identifier PXD006674.

Pelvic ring fractures in the elderly now and then – a pelvic registry study

OBJECTIVES To analyze the changes in demographic data stratified for age, sex and type of injury of elderly patients suffering from pelvic ring fractures over a 22-year observation period. DESIGN/SETTING Data has been collected prospectively, multi-centrically in hospitals participating in the German Pelvic Trauma Registry. PATIENTS We analyzed the data of 5665 patients with an age ≥60years included in the German Pelvic Trauma Registry from 1991 to 2013. KEY RESULTS Over the 22-year study period the frequency of type A fractures decreased significantly from 84.8% to 43.9%, while type C and, in particular, type B fractures significantly increased from 7.0% and 8.2% to 14.3% and 41.8%. In patients between 60 and 70 years of age the frequency of type B and C fractures was higher compared to patients >70years. The proportion of female patients, who represent the majority of the cohort (75%), was stable over the entire observation period. Interestingly, type A fractures were found more frequently in females, while type B and C fractures were found more frequently in males. CONCLUSIONS With the predicted demographic change and a shift toward more severe injury patterns (type B and C pelvic fractures) in the elderly population, trauma departments will need to develop specific surgical concepts for geriatric patients with pelvic ring fractures.

Stimulation of angiogenesis by cilostazol accelerates fracture healing in mice

Cilostazol, a selective phosphodiesterase‐3 inhibitor, is known to control cyclic adenosine monophosphate (c‐AMP) and to stimulate angiogenesis through upregulation of pro‐angiogenic factors. There is no information, however, whether cilostazol affects fracture healing. We, therefore, studied the effect of cilostazol on callus formation and biomechanics during fracture repair. Bone healing was analyzed in a murine femur fracture stabilized with an intramedullary screw. Radiological, biomechanical, histomorphometric, histochemical, and protein biochemical analyses were performed at 2 and 5 weeks after fracture. Twenty‐five mice received 30 mg/kg body weight cilostazol p.o. daily. Controls (n = 24) received equivalent amounts of vehicle. In cilostazol‐treated animals radiological analysis at 2 weeks showed an improved healing with an accelerated osseous bridging compared to controls. This was associated with a significantly higher amount of bony tissue and a smaller amount of cartilage tissue within the callus. Western blot analysis showed a higher expression of cysteine‐rich protein 61 (CYR61), bone morphogenetic protein (BMP)‐4, and receptor activator of NF‐kappaB ligand (RANKL). At 5 weeks, improved fracture healing after cilostazol treatment was indicated by biomechanical analyses, demonstrating a significant higher bending stiffness compared to controls. Thus, cilostazol improves fracture healing by accelerating both bone formation and callus remodeling.

A Minimally Invasive Model to Analyze Endochondral Fracture Healing in Mice Under Standardized Biomechanical Conditions

Bone healing models are necessary to analyze the complex mechanisms of fracture healing to improve clinical fracture treatment. During the last decade, an increased use of mouse models in orthopedic research was noted, most probably because mouse models offer a large number of genetically-modified strains and special antibodies for the analysis of molecular mechanisms of fracture healing. To control the biomechanical conditions, well-characterized osteosynthesis techniques are mandatory, also in mice. Here, we report on the design and use of a closed bone healing model to stabilize femur fractures in mice. The intramedullary screw, made of medical-grade stainless steel, provides through fracture compression an axial and rotational stability compared to the mostly used simple intramedullary pins, which show a complete lack of axial and rotational stability. The stability achieved by the intramedullary screw allows the analysis of endochondral healing. A large amount of callus tissue, received after stabilization with the screw, offers ideal conditions to harvest tissue for biochemical and molecular analyses. A further advantage of the use of the screw is the fact that the screw can be inserted into the femur with a minimally invasive technique without inducing damage to the soft tissue. In conclusion, the screw is a unique implant that can ideally be used in closed fracture healing models offering standardized biomechanical conditions.