Antibiotics in patients with severe burn injury-A modifiable variable in hypernatremia etiology.

INTRODUCTION: Hypernatremia is a common problem among patients with severe burn injuries and seems to be associated with an unfavorable clinical outcome. The current study was designed to evaluate the impact of antibiotics with a high proportion of sodium on this phenomenon. METHODS: All admissions to our burn center from 01/2017 till 06/2023 were retrospectively screened. All patients aged >18 years which suffered from at least 20 % total body surface burned area (TBSA) 2nd degree burn injuries or more than 10 % TBSA when including areas of 3rd degree burn injuries were included. The course of the serum Na-level was analyzed from two days before till two days after the start of the antibiotic treatment. Ampicillin/sulbactam, cefazoline and piperacillin/tazobactam were classified as high-dose sodium antibiotics (HPS), meropenem and vancomycin as low-dose sodium antibiotics (LPS). RESULTS: 120 patients met the inclusion criteria. A significant increase of the serum Na was detectable in the HPS group on day 1 and 2 after initiating the antibiotic treatment (n = 64, day 1: 2,1 (SD 4,18) mmol/l, p < 0,001; day 2: 2,44 (SD 5,26) mmol/l, p < 0,001) while no significant changes were detectable in the LPS group (n = 21, day 1: 0,18 (SD 7,45) mmol/l, p = 0,91; day 2: -0,27 (SD 7,44) mmol/l, p = 0,87). This effect was further aggravated when analyzing only the HPS patients with a TBSA ≥30 % (n = 33; day 1: 2,93 (SD 4,68) mmol/l, p = 0,002; day 2: 3,41 (SD 5,9) mmol/l, p = 0,003). CONCLUSION: The amount of sodium in antibiotics seems to have a relevant impact on the serum Na during the early stages of severe burn injury. Therefore, this aspect should be taken into account when searching for the most appropriate antibiotic treatment for patients with severe burn injury, especially when being at acute risk for a clinical relevant hypernatremia.

Sildenafil delays bone remodeling of fractured femora in aged mice by reducing the number and activity of osteoclasts within the callus tissue.

The elderly exhibit a reduced healing capacity after fracture, which is often associated with delayed or failed bone healing. This is due to a plethora of factors, such as an impaired bone vascular system and delayed angiogenesis. The phosphodiesterase-5 (PDE-5) inhibitor sildenafil exerts pro-angiogenic and pro-osteogenic effects. Hence, we herein investigated in aged mice whether sildenafil can improve fracture healing. For this purpose, 40 aged CD-1 mice (16-18 months) were daily treated with 5 mg/kg body weight sildenafil (n = 20) or vehicle (control, n = 20) by oral gavage. The callus tissue of their femora was analyzed at 2 and 5 weeks after fracture by X-ray, biomechanics, micro-computed tomography (µCT), histology, immunohistochemistry as well as Western blotting. These analyses revealed a significantly increased bone volume and higher ratio of callus to femoral bone diameter in sildenafil-treated mice at 5 weeks after fracture when compared to controls. This was associated with a reduced number and activity of osteoclasts at 2 weeks after fracture, most likely caused by an increased expression of osteoprotegerin (OPG). Taken together, these findings indicate that sildenafil does not improve fracture healing in the elderly but delays the process of bone remodeling most likely by reducing the number and activity of osteoclasts within the callus tissue.

Severe Burn Injuries - The Day the Sodium Starts Rising.

BACKGROUND/AIM: The current study was designed to evaluate the etiologies of hypernatremic episodes in patients with severe burn injuries in comparison to critically ill non-burn patients. PATIENTS AND METHODS: The retrospective data acquisition was limited to the first 14 days and to patients with at least 20% total body surface area (TBSA) 2nd degree burn injuries or more than 10% TBSA when including areas of 3rd degree burn injuries. The results were compared to the results of a previously published study that analyzed the risk factors for hypernatremia in 390 non-burn intensive care unit patients. RESULTS: In total, 120 patients with a total of 50 hypernatremic episodes were included. Compared to non-burn injury patients, no significant differences were detectable except for a lower rate of hypokalemia and a higher rate of mechanical ventilation. The main trigger for hypernatremic episodes was the loss of free water, while 24% of the hypernatremic episodes seemed to be at least partly triggered by a surplus sodium influx. Patients with hypernatremic episodes had a significantly higher mortality rate. However, in none of the cases was hypernatremia the decisive cause of death. CONCLUSION: Besides the unique phenomenon of high volume internal and external volume shifts, the overall risk factors and etiologies of hypernatremia in patients with severe burn injury do not seem to significantly differ from other ICU patient collectives. Remarkably, a surplus of sodium influx and therefore a modifiable factor besides the specific burn injury volume resuscitation had an impact on the hypernatremic episodes in 24% of cases.

[Nonunions after intertrochanteric and subtrochanteric femoral fractures]. / Pseudarthrosen nach per- und subtrochantären Femurfrakturen.

INTRODUCTION: The overall frequency of proximal femoral fractures means that we are repeatedly confronted with failed healing and implant failure, despite a relatively low nonunion rate especially in intertrochanteric fractures (< 5%). The aim of this paper is to present our approach to treating these nonunions of the proximal femur and discuss the treatment results. MATERIAL AND METHODS: Between 2009 and 2023, patients with nonunion of the proximal femur were retrospectively identified and analyzed. Age, gender, time to revision, the Weber-Cech classification of pseudarthrosis and radiographic imaging before and after revision were analyzed. RESULTS: A total of 66 patients were analyzed. The mean age was 58 years (range 25-88 years). The overall healing rate was 88% with a mean consolidation time of 8 months (range 2-29 months). The main osteosynthesis procedures were plate osteosynthesis (n = 45, of which 44 were blade plates), and nail replacement (n = 12). Other procedures included augmentative plate osteosyntheses (n = 4), isolated cancellous bone graft (n = 2), nail dynamization (n = 2), and the use of a dynamic hip screw (n = 1). DISCUSSION: The analysis of our treatment data as well as the current literature, revealed a trend towards intramedullary revision procedures. Implants that can be used to correct the CCD angle, such as the blade plate, remain a predictable option to achieve correction, especially in nonunions with an increased degree of varus. Particularly in the subtrochanteric region, fractures can also be treated in a targeted manner by a combination of mechanical and biological methods with a reamed nail change to a larger caliber implant.

Cilostazol Stimulates Angiogenesis and Accelerates Fracture Healing in Aged Male and Female Mice by Increasing the Expression of PI3K and RUNX2.

Fracture healing in the aged is associated with a reduced healing capacity, which often results in delayed healing or non-union formation. Many factors may contribute to this deterioration of bone regeneration, including a reduced 'angiogenic trauma response'. The phosphodiesterase-3 (PDE-3) inhibitor cilostazol has been shown to exert pro-angiogenic and pro-osteogenic effects in preclinical studies. Therefore, we herein analyzed in a stable closed femoral fracture model whether this compound also promotes fracture healing in aged mice. Forty-two aged CD-1 mice (age: 16-18 months) were daily treated with 30 mg/kg body weight cilostazol (n = 21) or vehicle (control, n = 21) by oral gavage. At 2 and 5 weeks after fracture, the femora were analyzed by X-ray, biomechanics, micro-computed tomography (µCT), histology, immunohistochemistry, and Western blotting. These analyses revealed a significantly increased bending stiffness at 2 weeks (2.2 ± 0.4 vs. 4.3 ± 0.7 N/mm) and an enhanced bone formation at 5 weeks (4.4 ± 0.7 vs. 9.1 ± 0.7 mm3) in cilostazol-treated mice when compared to controls. This was associated with a higher number of newly formed CD31-positive microvessels (3.3 ± 0.9 vs. 5.5 ± 0.7 microvessels/HPF) as well as an elevated expression of phosphoinositide-3-kinase (PI3K) (3.6 ± 0.8 vs. 17.4 ± 5.5-pixel intensity × 104) and runt-related transcription factor (RUNX)2 (6.4 ± 1.2 vs. 18.2 ± 2.7-pixel intensity × 104) within the callus tissue. These findings indicate that cilostazol accelerates fracture healing in aged mice by stimulating angiogenesis and the expression of PI3K and RUNX2. Hence, cilostazol may represent a promising compound to promote bone regeneration in geriatric patients.

Wearable activity data can predict functional recovery after musculoskeletal injury: Feasibility of a machine learning approach.

Delayed functional recovery after injury is associated with significant personal and socioeconomic burden. Identification of patients at risk for a prolonged recovery after a musculoskeletal injury is thus of high relevance. The aim of the current study was to show the feasibility of using a machine learning assisted model to predict functional recovery based on the pre- and immediate post injury patient activity as measured with wearable systems in trauma patients. Patients with a pre-existing wearable (smartphone and/or body-worn sensor), data availability of at least 7 days prior to their injury, and any musculoskeletal injury of the upper or lower extremity were included in this study. Patient age, sex, injured extremity, time off work and step count as activity data were recorded continuously both pre- and post-injury. Descriptive statistics were performed and a logistic regression machine learning model was used to predict the patient's functional recovery status after 6 weeks based on their pre- and post-injury activity characteristics. Overall 38 patients (7 upper extremity, 24 lower extremity, 5 pelvis, 2 combined) were included in this proof-of-concept study. The average follow-up with available wearable data was 85.4 days. Based on the activity data, a predictive model was constructed to determine the likelihood of having a recovery of at least 50 % of the pre-injury activity state by post injury week 6. Based on the individual activity by week 3 a predictive accuracy of over 80 % was achieved on an independent test set (F1=0,82; AUC=0,86; ACC=8,83). The employed model is feasible to assess the principal risk for a slower recovery based on readily available personal wearable activity data. The model has the potential to identify patients requiring additional aftercare attention early during the treatment course, thus optimizing return to the pre-injury status through focused interventions. Additional patient data is needed to adapt the model to more specifically focus on different fracture entities and patient groups.

Advantages and Limitations of Diabetic Bone Healing in Mouse Models: A Narrative Review.

Diabetes represents a major risk factor for impaired fracture healing. Type 2 diabetes mellitus is a growing epidemic worldwide, hence an increase in diabetes-related complications in fracture healing can be expected. However, the underlying mechanisms are not yet completely understood. Different mouse models are used in preclinical trauma research for fracture healing under diabetic conditions. The present review elucidates and evaluates the characteristics of state-of-the-art murine diabetic fracture healing models. Three major categories of murine models were identified: Streptozotocin-induced diabetes models, diet-induced diabetes models, and transgenic diabetes models. They all have specific advantages and limitations and affect bone physiology and fracture healing differently. The studies differed widely in their diabetic and fracture healing models and the chosen models were evaluated and discussed, raising concerns in the comparability of the current literature. Researchers should be aware of the presented advantages and limitations when choosing a murine diabetes model. Given the rapid increase in type II diabetics worldwide, our review found that there are a lack of models that sufficiently mimic the development of type II diabetes in adult patients over the years. We suggest that a model with a high-fat diet that accounts for 60% of the daily calorie intake over a period of at least 12 weeks provides the most accurate representation.

Parathyroid hormone stimulates bone regeneration in an atrophic non-union model in aged mice.

BACKGROUND: Non-union formation still represents a major burden in trauma and orthopedic surgery. Moreover, aged patients are at an increased risk for bone healing failure. Parathyroid hormone (PTH) has been shown to accelerate fracture healing in young adult animals. However, there is no information whether PTH also stimulates bone regeneration in atrophic non-unions in the aged. Therefore, the aim of the present study was to analyze the effect of PTH on bone regeneration in an atrophic non-union model in aged CD-1 mice. METHODS: After creation of a 1.8 mm segmental defect, mice femora were stabilized by pin-clip fixation. The animals were treated daily with either 200 mg/kg body weight PTH 1-34 (n = 17) or saline (control; n = 17) subcutaneously. Bone regeneration was analyzed by means of X-ray, biomechanics, micro-computed tomography (µCT) imaging as well as histological, immunohistochemical and Western blot analyses. RESULTS: In PTH-treated animals bone formation was markedly improved when compared to controls. This was associated with an increased bending stiffness as well as a higher number of tartrate-resistant acid phosphatase (TRAP)-positive osteoclasts and CD31-positive microvessels within the callus tissue. Furthermore, PTH-treated aged animals showed a decreased inflammatory response, characterized by a lower number of MPO-positive granulocytes and CD68-positive macrophages within the bone defects when compared to controls. Additional Western blot analyses demonstrated a significantly higher expression of cyclooxygenase (COX)-2 and phosphoinositide 3-kinase (PI3K) in PTH-treated mice. CONCLUSION: Taken together, these findings indicate that PTH is an effective pharmacological compound for the treatment of non-union formation in aged animals.

On the Fluorescence Properties and Nonradiative Transitions in Medium-Sized All-Trans Polyenes.

The nonadiabatic photodynamics of all-trans linear polyenes with N = 4-8 conjugated double bonds is studied from an electronic structure perspective. Excitation energies and stationary points for the 1Bu and 2Ag singlet states have been computed by using the state-average complete active space (SA-CASSCF) method and its second-order perturbation theory variant (MS-CASPT2). The dependence of the two low-lying excited states on the "chain length" N has been elucidated. In addition, the 1Bu-2Ag crossing seam has been mapped out in a suitable two-dimensional coordinate space and its minimum within the subspace has been determined. This minimum is found to increase substantially and monotonously in energy with increasing N. This increase is discussed and interpreted in relation to the fluorescence properties of these systems. In particular, it allows to understand the crossover from S1(2Ag) fluorescence for smaller N to S2(1Bu) (or dual) fluorescence for larger N.

Nature of Hops, Coordinates, and Detailed Balance for Nonadiabatic Simulations in the Condensed Phase.

Photoinduced processes play a crucial role in a multitude of important molecular phenomena. Accurately modeling these processes in an environment other than a vacuum requires a detailed description of the electronic states involved as well as how energy flows are coupled to the surroundings. Nonadiabatic effects must also be included in order to describe the exchange of energy between electronic and nuclear degrees of freedom correctly. In this work, we revisit the ring-opening reaction 1,3-cylohexadiene (CHD) in a solvent environment. Using our newly developed Interface for Non-Adiabatic Quantum mechanics/molecular mechanics in Solvent (INAQS) we trace the evolution of the reaction via hybrid quantum mechanics/molecular mechanics (QM/MM) surface hopping with a focus on the solvent's participation in the nonadiabatic relaxation process and the long-time approach to equilibrium. We explicitly include the MM solvent contribution to the nonadiabatic coupling vector─enabling an accurate approach to equilibrium at long times─and find that in highly multidimensional systems gradients can have little or nothing to do with the nonadiabatic couplings.

Translational evaluation of gait behavior in rodent models of arthritic disorders with the CatWalk device - a narrative review.

Arthritic disorders have become one of the main contributors to the global burden of disease. Today, they are one of the leading causes of chronic pain and disability worldwide. Current therapies are incapable of treating pain sufficiently and preventing disease progression. The lack of understanding basic mechanisms underlying the initiation, maintenance and progression of arthritic disorders and related symptoms represent the major obstacle in the search for adequate treatments. For a long time, histological evaluation of joint pathology was the predominant outcome parameter in preclinical arthritis models. Nevertheless, quantification of pain and functional limitations analogs to arthritis related symptoms in humans is essential to enable bench to bedside translation and to evaluate the effectiveness of new treatment strategies. As the experience of pain and functional deficits are often associated with altered gait behavior, in the last decades, automated gait analysis has become a well-established tool for the quantitative evaluation of the sequalae of arthritic disorders in animal models. The purpose of this review is to provide a detailed overview on the current literature on the use of the CatWalk gait analysis system in rodent models of arthritic disorders, e.g., Osteoarthritis, Monoarthritis and Rheumatoid Arthritis. Special focus is put on the assessment and monitoring of pain-related behavior during the course of the disease. The capability of evaluating the effect of distinct treatment strategies and the future potential for the application of the CatWalk in rodent models of arthritic disorders is also addressed in this review. Finally, we discuss important consideration and provide recommendations on the use of the CatWalk in preclinical models of arthritic diseases.

Cilostazol promotes blood vessel formation and bone regeneration in a murine non-union model.

Non-unions represent a major complication in trauma and orthopedic surgery. Many factors contribute to bone regeneration, out of which an adequate vascularization has been recognized as crucial. The phosphodiesterase-3 (PDE-3) inhibitor cilostazol has been shown to exert pro-angiogenic and pro-osteogenic effects in a variety of preclinical studies. Hence, we herein investigated the effects of cilostazol on bone regeneration in an atrophic non-union model in mice. For this purpose, a 1.8 mm femoral segmental defect was stabilized by pin-clip fixation and the animals were treated daily with 30 mg/kg body weight cilostazol or saline (control) per os. At 2, 5 and 10 weeks after surgery the healing of femora was analyzed by X-ray, biomechanics, photoacoustic imaging, and micro-computed tomography (µCT). To investigate the cellular composition and the growth factor expression of the callus tissue additional histological, immunohistochemical and Western blot analyses were performed. Cilostazol-treated animals showed increased bone formation within the callus, resulting in an enhanced bending stiffness when compared to controls. This was associated with a more pronounced expression of vascular endothelial growth factor (VEGF), a higher number of CD31-positive microvessels and an increased oxygen saturation within the callus tissue. Furthermore, cilostazol induced higher numbers of tartrate-resistant acidic phosphate (TRAP)-positive osteoclasts and CD68-positive macrophages. Taken together, these findings demonstrate that cilostazol is a promising drug candidate for the adjuvant treatment of atrophic non-unions in clinical practice.

"Fall Risk Scoring" in Outpatient Gait Analysis: Validation of a New Fall Risk Assessment for Nursing Home Residents. / "Fall Risk Scoring" in der ambulanten Ganganalyse: Validierung eines neuen Sturzrisikoassessments bei Heimbewohnern.

Falls in senior home residents are common. Individual preventive training can lower the fall risk. To detect the need for training, a systematic assessment of the individual fall risk is needed. The aim of this study was thus to assess whether a fall risk score based on free field insole measurements can distinguish between an at-risk group of senior home residents and a healthy young control group. A published fall risk score was used in senior home residents over the age of 75 and a young (< 40 years) control group to determine the individual fall risk. In addition, the fall events over 12 months were assessed. Statistical analysis including ROC analysis was performed to determine the ability of the score to detect participants at heightened fall risk. In total, 18 nursing home residents and 9 young control participants were included. Of the nursing home residents, 15 had at least one fall, with a total of 37 falls recorded over 12 months. In the control group, no falls were recorded. The fall risk score was significantly different between nursing home residents and the control group (9.2 + 3.2 vs. 5.7 ± 2.2). Furthermore, the score significantly differentiated fallers from non-fallers (10.3 ± 1.8 vs. 5.2 ± 2.5), with a cut-off > 7.5 (AUC: 0.95) and a sensitivity of 86.7% (specificity 83.3%). The fall risk score is able to detect the difference between senior nursing home residents and young, healthy controls, as well as between fallers and non-fallers. Its main proof of concept is demonstrated, as based on movement data outside special gait labs, and it can simplify the risk of fall determination in geriatric nursing home residents and can now be used in further, prospective studies.

Sildenafil, a phosphodiesterase-5 inhibitor, stimulates angiogenesis and bone regeneration in an atrophic non-union model in mice.

Non-union formation represents a major complication in trauma and orthopedic surgery. The phosphodiesterase-5 (PDE-5) inhibitor sildenafil has been shown to exert pro-angiogenic and pro-osteogenic effects in vitro and in vivo. Therefore, the aim of the present study was to analyze the impact of sildenafil in an atrophic non-union model in mice. After creation of a 1.8 mm segmental defect, mice femora were stabilized by pin-clip fixation. Bone regeneration was analyzed by means of X-ray, biomechanics, photoacoustic and micro-computed tomography (µCT) imaging as well as histological, immunohistochemical and Western blot analyses at 2, 5 and 10 weeks after surgery. The animals were treated daily with either 5 mg/kg body weight sildenafil (n = 35) or saline (control; n = 35) per os. Bone formation was markedly improved in defects of sildenafil-treated mice when compared to controls. This was associated with a higher bending stiffness as well as an increased number of CD31-positive microvessels and a higher oxygen saturation within the callus tissue. Moreover, the bone defects of sildenafil-treated animals contained more tartrate-resistant acid phosphatase (TRAP)-positive osteoclasts and CD68-positive macrophages and exhibited a higher expression of the pro-angiogenic and pro-osteogenic markers cysteine rich protein (CYR)61 and vascular endothelial growth factor (VEGF) when compared to controls. These findings demonstrate that sildenafil acts as a potent stimulator of angiogenesis and bone regeneration in atrophic non-unions.

Diclofenac, a NSAID, delays fracture healing in aged mice.

Nonsteroidal anti-inflammatory drugs (NSAIDs), such as diclofenac, belong to the most prescribed analgesic medication after traumatic injuries. However, there is accumulating evidence that NSAIDs impair fracture healing. Because bone regeneration in aged patients is subject to significant changes in cell differentiation and proliferation as well as a markedly altered pharmacological action of drugs, we herein analyzed the effects of diclofenac on bone healing in aged mice using a stable closed femoral facture model. Thirty-three mice (male n = 14, female n = 19) received a daily intraperitoneal injection of diclofenac (5 mg/kg body weight). Vehicle-treated mice (n = 29; male n = 13, female n = 16) served as controls. Fractured mice femora were analyzed by means of X-ray, biomechanics, micro computed tomography (µCT), histology and Western blotting. Biomechanical analyses revealed a significantly reduced bending stiffness in diclofenac-treated animals at 5 weeks after fracture when compared to vehicle-treated controls. Moreover, the callus tissue in diclofenac-treated aged animals exhibited a significantly reduced amount of bone tissue and higher amounts of fibrous tissue. Further histological analyses demonstrated less lamellar bone after diclofenac treatment, indicating a delay in callus remodeling. This was associated with a decreased number of osteoclasts and an increased expression of osteoprotegerin (OPG) during the early phase of fracture healing. These findings indicate that diclofenac delays fracture healing in aged mice by affecting osteogenic growth factor expression and bone formation as well as osteoclast activity and callus remodeling.

Intermittent Exposure to a 16 Hz Extremely Low Frequency Pulsed Electromagnetic Field Promotes Osteogenesis In Vitro through Activating Piezo 1-Induced Ca2+ Influx in Osteoprogenitor Cells.

Exposure to extremely low frequency pulsed electromagnetic fields (ELF-PEMF) is supposed to simulate local EMF generated during mechanical stimulation of bone and may therefore be used to improve bone regeneration. This study aimed at optimizing the exposure strategy and investigating the underlying mechanisms of a 16 Hz ELF-PEMF, previously reported to boost osteoblast function. Comparing influences of daily continuous (30 min every 24 h) and intermittent (10 min every 8 h) exposure to the 16 Hz ELF-PEMF on osteoprogenitor cells revealed that the intermittent exposure strategy enhanced the 16 Hz ELF-PEMF effects regarding cell numbers and osteogenic function. Gene expression of piezo 1 and related Ca2+ influx were significantly increased in SCP-1 cells with the daily intermittent exposure. Pharmacological inhibition of piezo 1 with Dooku 1 largely abolished the positive effect of the 16 Hz ELF-PEMF exposure on osteogenic maturation of SCP-1 cells. In summary, the intermittent exposure strategy enhanced the positive effects of 16 Hz continuous ELF-PEMF exposure in terms of cell viability and osteogenesis. This effect was shown to be mediated by an increased expression of piezo 1 and related Ca2+ influx. Thus, the intermittent exposure strategy is a promising way to further optimize the therapeutic effects of the 16 Hz ELF-PEMF regarding fracture healing or osteoporosis.

"Bring Your Own Device"-A New Approach to Wearable Outcome Assessment in Trauma.

Background and Objectives: Outcome data from wearable devices are increasingly used in both research and clinics. Traditionally, a dedicated device is chosen for a given study or clinical application to collect outcome data as soon as the patient is included in a study or undergoes a procedure. The current study introduces a new measurement strategy, whereby patients' own devices are utilized, allowing for both a pre-injury baseline measure and ability to show achievable results. Materials and Methods: Patients with a pre-existing musculoskeletal injury of the upper and lower extremity were included in this exploratory, proof-of-concept study. They were followed up for a minimum of 6 weeks after injury, and their wearable outcome data (from a smartphone and/or a body-worn sensor) were continuously acquired during this period. A descriptive analysis of the screening characteristics and the observed and achievable outcome patterns was performed. Results: A total of 432 patients was continuously screened for the study, and their screening was analyzed. The highest success rate for successful inclusion was in younger patients. Forty-eight patients were included in the analysis. The most prevalent outcome was step count. Three distinctive activity data patterns were observed: patients recovering, patients with slow or no recovery, and patients needing additional measures to determine treatment outcomes. Conclusions: Measuring outcomes in trauma patients with the Bring Your Own Device (BYOD) strategy is feasible. With this approach, patients were able to provide continuous activity data without any dedicated equipment given to them. The measurement technique is especially suited to particular patient groups. Our study's screening log and inclusion characteristics can help inform future studies wishing to employ the BYOD design.

Radiographic, Biomechanical and Histological Characterization of Femoral Fracture Healing in Aged CD-1 Mice.

With a gradually increasing elderly population, the treatment of geriatric patients represents a major challenge for trauma and reconstructive surgery. Although, it is well established that aging affects bone metabolism, it is still controversial if aging impairs bone healing. Accordingly, we investigated fracture healing in young adult (3-4 months) and aged (16-18 months) CD-1 mice using a stable closed femoral fracture model. Bone healing was analyzed by radiographic, biomechanical and histological analysis at 1, 2, 3, 4 and 5 weeks after fracture. Our results demonstrated an increased callus diameter to femoral diameter ratio in aged animals at later time points of fracture healing when compared to young adult mice. Moreover, our biomechanical analysis revealed a significantly decreased bending stiffness at 3 and 4 weeks after fracture in aged animals. In contrast, at 5 weeks after fracture, the analysis showed no significant difference in bending stiffness between the two study groups. Additional histological analysis showed a delayed endochondral ossification in aged animals as well as a higher amounts of fibrous tissue at early healing time points. These findings indicate a delayed process of callus remodeling in aged CD-1 mice, resulting in a delayed fracture healing when compared to young adult animals. However, the overall healing capacity of the fractured femora was not affected by aging.

Bone Healing Gone Wrong: Pathological Fracture Healing and Non-Unions-Overview of Basic and Clinical Aspects and Systematic Review of Risk Factors.

Bone healing is a multifarious process involving mesenchymal stem cells, osteoprogenitor cells, macrophages, osteoblasts and -clasts, and chondrocytes to restore the osseous tissue. Particularly in long bones including the tibia, clavicle, humerus and femur, this process fails in 2-10% of all fractures, with devastating effects for the patient and the healthcare system. Underlying reasons for this failure are manifold, from lack of biomechanical stability to impaired biological host conditions and wound-immanent intricacies. In this review, we describe the cellular components involved in impaired bone healing and how they interfere with the delicately orchestrated processes of bone repair and formation. We subsequently outline and weigh the risk factors for the development of non-unions that have been established in the literature. Therapeutic prospects are illustrated and put into clinical perspective, before the applicability of biomarkers is finally discussed.

Weight-bearing Restrictions after Distal Femur Fractures - Review of Current Literature. / Belastungsvorgaben nach distaler Femurfraktur - eine aktuelle Literaturübersicht.

The incidence of distal femur fractures increases in the geriatric patient. The primary treatment goal in these fractures is early mobilisation to prevent secondary injuries associated with immobility. In light of the increasing spectrum of therapeutic options for postoperative fracture treatment, including double plating, nail-plate combination and distal femur replacement as postoperative treatments, weight-bearing recommendations are becoming increasingly important. The aim of this study was thus to analyse the weight-bearing recommendations and associated therapy results within the literature of the past 9 years and compare the recommendations to our own approach.