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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.
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Inhibidores de Fosfodiesterasa 5 , Factor A de Crecimiento Endotelial Vascular , Animales , Ratones , Citrato de Sildenafil/farmacología , Citrato de Sildenafil/uso terapéutico , Inhibidores de Fosfodiesterasa 5/farmacología , Inhibidores de Fosfodiesterasa 5/uso terapéutico , Fosfodiesterasas de Nucleótidos Cíclicos Tipo 5 , Microtomografía por Rayos X , Regeneración Ósea , AtrofiaRESUMEN
BACKGROUND AND PURPOSE: In fracture healing, ischemia caused by vascular injuries, chronic vascular diseases, and metabolic comorbidities is one of the major risk factors for delayed union and non-union formation. To gain novel insights into the molecular and cellular pathology of ischemic fracture healing, appropriate animal models are needed. Murine models are of particular interest, as they allow to study the molecular aspects of fracture healing due to the availability of both a large number of murine antibodies and gene-targeted animals. Thus, we present the development of an ischemic fracture healing model in mice. MATERIAL AND METHODS: After inducing a mild ischemia by double ligature of the deep femoral artery in CD-1 mice, the ipsilateral femur was fractured by a 3-point bending device and stabilized by screw osteosynthesis. In control animals, the femur was fractured and stabilized without the induction of ischemia. The femora were analyzed at 2 and 5 weeks after fracture healing by means of radiology, biomechanics, histology, and histomorphometry. RESULTS: The surgically induced ischemia delayed and impaired the process of fracture healing. This was indicated by a lower Goldberg score, decreased bending stiffness, and reduced bone callus formation in the ischemic animals when compared with the controls. INTERPRETATION: We introduce a novel ischemic femoral fracture healing model in mice, which is characterized by delayed bone healing. In future, the use of this model may allow both the elucidation of the molecular aspects of ischemic fracture healing and the study of novel treatment strategies.
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Fracturas del Fémur , Curación de Fractura , Animales , Callo Óseo , Fracturas del Fémur/cirugía , Fijación Interna de Fracturas , Humanos , Isquemia , RatonesRESUMEN
Diabetes mellitus is a main risk factor for delayed fracture healing and fracture non-unions. Successful fracture healing requires stimuli from different immune cells, known to be affected in diabetics. Especially, application of mononuclear cells has been proposed to promote wound and fracture healing. Thus, aim was to investigate the effect of pre-/diabetic conditions on mononuclear cell functions essential to promote osteoprogenitor cell function. We here show that pre-/diabetic conditions suppress the expression of chemokines, e.g., CCL2 and CCL8 in osteoprogenitor cells. The associated MCP-1 and MCP-2 were significantly reduced in serum of diabetics. Both MCPs chemoattract mononuclear THP-1 cells. Migration of these cells is suppressed under hyperglycemic conditions, proposing that less mononuclear cells invade the site of fracture in diabetics. Further, we show that the composition of cytokines secreted by mononuclear cells strongly differ between diabetics and controls. Similar is seen in THP-1 cells cultured under hyperinsulinemia or hyperglycemia. The altered secretome reduces the positive effect of the THP-1 cell conditioned medium on migration of osteoprogenitor cells. In summary, our data support that factors secreted by mononuclear cells may support fracture healing by promoting migration of osteoprogenitor cells but suggest that this effect might be reduced in diabetics.
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Medios de Cultivo Condicionados/metabolismo , Diabetes Mellitus/metabolismo , Curación de Fractura , Monocitos/metabolismo , Animales , Biomarcadores , Movimiento Celular , Células Cultivadas , Quimiocina CCL2/genética , Quimiocina CCL2/metabolismo , Quimiocina CCL8/metabolismo , Quimiocinas/metabolismo , Quimiotaxis de Leucocito/inmunología , Humanos , Hiperglucemia/metabolismo , Leucocitos Mononucleares/inmunología , Leucocitos Mononucleares/metabolismo , Sistema de Señalización de MAP Quinasas , Monocitos/inmunología , Osteoblastos/metabolismo , Osteogénesis , Células THP-1RESUMEN
PURPOSE: Secondary hip osteoarthritis after acetabular fractures requiring total arthroplasty (THA) poses a huge burden on the affected patients as well as health systems. The present study aimed to assess risk factors associated with THA after acetabular fractures based on the data from the German Pelvic Trauma Registry. METHODS: Retrospective analysis of 678 acetabular fracture cases without concomitant pelvic ring fracture treated and followed-up between January 2004 and May 2015 at six large trauma centres. Multivariate Cox regression analysis was performed assessing the association of patient/treatment characteristics with THA likelihood at an average follow-up of 2.7 years (range 0.4-9.5 years; SD 1.8 years). RESULTS: Overall, the rate of secondary osteoarthritis was 19.8%. The likelihood for THA increased with 6% per age year (95% CI 1.04-1.09) and with 21% per millimetre subluxation (95%CI 1.09-1.33). This likelihood was 3.54 (95% CI 1.77-7.08) and 3.68 times (95% CI 1.87-7.47) higher if the posterior wall was involved and a contusion and/or impaction of the femoral head was present. Other covariates (sex, ISS, trauma type, AO/OTA and Letournel classification, initial displacement, surgical approach, intra-articular fragments, contusion and/or impaction to the acetabulum, reduction, intervention type, duration of surgery, soft tissue damage, residual fracture step/gap, and prevention of heterotopic ossifications) were not significantly associated (p > 0.15). CONCLUSIONS: Twenty percent of patients with acetabular fractures require THA. The associated risk factors are patient age, femoral head lesion/subluxation, and involvement of the posterior wall. The identified risk factors support previous research and should be minded when treatment of acetabular fractures is planned.
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Acetábulo/lesiones , Fracturas Óseas/complicaciones , Osteoartritis de la Cadera/etiología , Acetábulo/cirugía , Adulto , Anciano , Artroplastia de Reemplazo de Cadera , Bélgica , Costo de Enfermedad , Femenino , Fracturas Óseas/cirugía , Alemania , Humanos , Masculino , Persona de Mediana Edad , Osteoartritis de la Cadera/cirugía , Sistema de Registros , Estudios Retrospectivos , Factores de RiesgoRESUMEN
PURPOSE: The aim of the current study was to describe long-term gait changes after talus fractures, identify patterns associated with poor outcome and discuss possible treatment options based on dynamic gait analysis. METHODS: Twenty-seven patients were followed-up clinically and via gait analysis after talus fracture osteosynthesis. Continuous dynamic pedobarography with a gait analysis insole was performed on a standardized parcours consisting of different gait tasks and matched to the outcome. RESULTS: Mean follow-up was 78.3 months (range 21-150), mean AOFAS and Olerud-Molander scores 66 (range 20-100) and 54 (range 15-100). Significant correlations between fracture classification and osteoarthritis (Hawkins: rs = 0.67 / Marti-Weber: rs = 0.5) as well as several gait differences between injured and healthy foot with correlations to outcome were seen: decreased step load-integral/maximum-load; associations between centre-of-pressure displacement and outcome as well as between temporospatial measures and outcome. Overall, pressure-distribution was lateralized in patients with subtalar joint injury (Δ: 0.5765 N/cm2, p = 0.0475). CONCLUSIONS: Talus fractures lead to chronic gait changes and restricted function. Dynamic pedobarography can identify patterns associated with poor results. The observed gait patterns suggest that changes can be addressed by physical therapy and customized orthoses to improve overall outcome. The presented insole and measurement protocol are immediately feasible as a diagnostic and rehabilitation aid.
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Fracturas de Tobillo/fisiopatología , Fijación Interna de Fracturas/métodos , Análisis de la Marcha/métodos , Marcha/fisiología , Adulto , Anciano , Anciano de 80 o más Años , Fracturas de Tobillo/cirugía , Estudios de Seguimiento , Ortesis del Pié/estadística & datos numéricos , Humanos , Persona de Mediana Edad , Estudios Retrospectivos , Astrágalo/lesionesRESUMEN
BACKGROUND: With the demographic change, the treatment of elderly patients has become a major issue for health systems worldwide. AIMS: The aim of this study was to analyze the change in the rate of surgical treatment of pelvic ring fractures in patients with an age of ≥60 years over a 22-year period depending on fracture type, age and sex. METHODS: Data of 5665 patients with an age of ≥60 years, who were treated for pelvic ring fractures from 1991 to 2013 in one of 31 hospitals participating in the German Pelvic Trauma Registry, were included. The registry is divided into four time periods: t 1 = 1991-1993, t 2 = 1997-2000, t 3 = 2001-2008 and t 4 = 2009-2013. Data had been collected prospectively and was analyzed retrospectively, stratified for age and sex of the patients as well as type of fracture and mode of therapy (surgical vs. conservative). RESULTS: There was a significant increase (p < 0.05) in the overall rate of surgical treatment. Nonetheless, during all time periods patients with an age of >70 years were significantly less frequently surgically treated compared to 60- to 70-year-olds. Regardless of the fracture type, the rate of surgical treatment was significantly higher (p < 0.05) in male compared to female patients during t 1. While this difference persisted for type A and type B fractures, the frequency of surgical treatment of type C fractures approximated in males and females. CONCLUSIONS: The present data indicate that the rate of surgical treatment of pelvic ring fractures in elderly patients has significantly increased over the 22-year period. Nonetheless, older patients (>70 years) as well as female patients are still less frequently surgically treated.
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Fracturas Óseas/cirugía , Procedimientos Ortopédicos/estadística & datos numéricos , Huesos Pélvicos/lesiones , Anciano , Anciano de 80 o más Años , Femenino , Fracturas Óseas/clasificación , Fracturas Óseas/epidemiología , Humanos , Estudios Longitudinales , Masculino , Prótesis e Implantes , Sistema de Registros , Estudios RetrospectivosRESUMEN
PURPOSE: Rehabilitation after lower-extremity fractures is based on the physicians' recommendation for non-, partial-, or full weight-bearing. Clinical studies rely on this assumption, but continuous compliance or objective loading rates are unknown. The purpose of this study was to determine the compliance to weight-bearing recommendations by introducing a novel, pedobarography system continuously registering postoperative ground forces into ankle, tibial shaft and proximal femur fracture aftercare and test its feasibility for this purpose. METHODS: In this prospective, observational study, a continuously measuring pedobarography insole was placed in the patients shoe during the immediate post-operative aftercare after ankle, tibial shaft and intertrochanteric femur fractures. Weight-bearing was ordered as per the institutional standard and controlled by physical therapy. The insole was retrieved after a maximum of six weeks (28 days [range 5-42 days]). Non-compliance was defined as a failure to maintain, or reach the ordered weight-bearing within 30%. RESULTS: Overall 30 patients were included in the study. Fourteen (47%) of the patients were compliant to the weight-bearing recommendations. Within two weeks after surgery patients deviated from the recommendation by over 50%. Sex, age and weight did not influence the performance (p > 0.05). Ankle fracture patients (partial weight-bearing) showed a significantly increased deviation from the recommendation (p = 0.01). CONCLUSIONS: Our study results show that, despite physical therapy training, weight-bearing compliance to recommended limits was low. Adherence to the partial weight-bearing task was further decreased over time. Uncontrolled weight-bearing recommendations should thus be viewed with caution and carefully considered as fiction. The presented insole is feasible to determine weight bearing continuously, could immediately help define real-time patient behaviour and establish realistic, individual weight-bearing recommendations.
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Ortesis del Pié/estadística & datos numéricos , Fracturas Óseas/cirugía , Marcha/fisiología , Cooperación del Paciente/estadística & datos numéricos , Soporte de Peso , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Huesos de la Extremidad Inferior/lesiones , Femenino , Humanos , Masculino , Persona de Mediana Edad , Modalidades de Fisioterapia , Periodo Posoperatorio , Estudios Prospectivos , Adulto JovenRESUMEN
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 (<â¯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 (nâ¯= 45, of which 44 were blade plates), and nail replacement (nâ¯= 12). Other procedures included augmentative plate osteosyntheses (nâ¯= 4), isolated cancellous bone graft (nâ¯= 2), nail dynamization (nâ¯= 2), and the use of a dynamic hip screw (nâ¯= 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.
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Fijación Interna de Fracturas , Fracturas no Consolidadas , Fracturas de Cadera , Humanos , Anciano , Femenino , Masculino , Persona de Mediana Edad , Anciano de 80 o más Años , Adulto , Fracturas de Cadera/cirugía , Fracturas de Cadera/diagnóstico por imagen , Fijación Interna de Fracturas/métodos , Fracturas no Consolidadas/cirugía , Fracturas no Consolidadas/diagnóstico por imagen , Estudios Retrospectivos , Resultado del Tratamiento , Placas Óseas , Reoperación , Fracturas del Fémur/cirugía , Fracturas del Fémur/diagnóstico por imagenRESUMEN
The diagnosis and treatment of non-unions still represents an interdisciplinary challenge. Therefore, prevention, early detection and specific treatment are of great importance. Non-unions of the upper extremities, although less common than that of the lower extremities, requires special attention for successful treatment due to the central role of the shoulder girdle and arm in day to day activities. Successful treatment of non-unions requires a comprehensive evaluation of the patient's medical history, a thorough clinical examination and in particular radiological imaging. In order to effectively treat the pseudarthrosis it is crucial to distinguish between pseudarthroses that are suspected to be due to infections and those that are not. This article presents a treatment algorithm for managing both pseudarthrosis due to infection and pseudarthrosis without infection in the upper extremities.
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Seudoartrosis , Humanos , Seudoartrosis/diagnóstico por imagen , Fracturas no Consolidadas/diagnóstico por imagen , Fracturas no Consolidadas/cirugía , Algoritmos , Extremidad Superior , RadiografíaRESUMEN
Early and reliable detection of infection is vital for successful treatment. Serum markers such as C-reactive protein (CRP) and procalcitonin (PCT) are known to increase with a time lag. Azurocidin 1 (AZU1) has emerged as a promising marker for septic patients, but its diagnostic value in orthopedic and trauma patients remains unexplored. Between July 2020 and August 2023, all patients necessitating inpatient treatment for periprosthetic joint infection (PJI), peri-implant infection (II), soft tissue infection, chronic osteomyelitis, septic arthrodesis, bone non-union with and without infection were enrolled. Patients undergoing elective total joint arthroplasty (TJA) served as the control group. Blood samples were collected and analyzed for CRP, white blood cell count (WBC), PCT, and AZU1. Based on the inclusion and exclusion criteria 222 patients were included in the study (trauma = 38, soft tissue infection = 75, TJA = 33, PJI/II = 39, others = 37). While sensitivity and specificity were comparably high for AZU1 (0.734/0.833), CRP and PCT had higher specificity (0.542/1 and 0.431/1, respectively), and WBC a slightly higher sensitivity (0.814/0.455) for septic conditions. Taken together, the area under the curve (AUC) showed the highest accuracy for AZU1 (0.790), followed by CRP (0.776), WBC (0.641), and PCT (0.656). The Youden-Index was 0.57 for AZU1, 0.54 for CRP, 0.27 for WBC, and 0.43 for PCT. Elevated AZU1 levels effectively distinguished patients with a healthy condition from those suffering from infection. However, there is evidence suggesting that trauma may influence the release of AZU1. Additional research is needed to validate the diagnostic value of this new biomarker and further explore its potential clinical applications.
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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 5â¯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.
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Fracturas del Fémur , Osteoclastos , Humanos , Ratones , Animales , Anciano , Citrato de Sildenafil/farmacología , Citrato de Sildenafil/uso terapéutico , Microtomografía por Rayos X , Fracturas del Fémur/diagnóstico por imagen , Fracturas del Fémur/tratamiento farmacológico , Curación de Fractura , Remodelación Ósea , Inhibidores de Fosfodiesterasa 5/farmacologíaRESUMEN
Open reduction and internal fixation are the gold standard for the treatment of dislocated acetabular fractures. A primary joint replacement is only justified in isolated cases. The indications are merely non-reconstructable acetabular fractures, accompanying displaced fractures of the femoral neck and non-reconstructable fractures of the femoral head.Because of the difficulties in achieving sufficient cup stability, joint replacement for the treatment of acetabular fractures regularly requires implants designed for revision arthroplasty. The Kocher-Langenbeck approach provides the most versatile options, as it enables simultaneous stabilization of the dorsal acetabular structures, which are essential for the stability of the cup.For primary joint replacement as a treatment of acetabular fractures, survival of the prosthetic cup is markedly worse when compared to elective primary joint replacement. Particularly in younger patients but also in aged patients, every effort should be made to achieve a press fit of the cup. In most cases, this will include reduction and fixation of the fracture for stabilization of the acetabulum prior to joint replacement. A staged approach with an early secondary replacement intervention seems to provide better overall results than simultaneous fracture fixation and joint replacement.
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Artroplastia de Reemplazo de Cadera , Fracturas de Cadera , Fracturas de la Columna Vertebral , Humanos , Anciano , Artroplastia de Reemplazo de Cadera/métodos , Fracturas de Cadera/cirugía , Acetábulo/diagnóstico por imagen , Fijación Interna de Fracturas/métodos , Fracturas de la Columna Vertebral/cirugíaRESUMEN
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.
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Fracturas Femorales Distales , Fracturas del Fémur , Humanos , Anciano , Fracturas del Fémur/diagnóstico por imagen , Fracturas del Fémur/cirugía , Fijación Interna de Fracturas/métodos , Fémur , Soporte de Peso , Placas ÓseasRESUMEN
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.
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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.
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Chronic wounds affect more than 2% of the population worldwide, with a significant burden on affected individuals, healthcare systems, and societies. A key regulator of the entire wound healing cascade is transforming growth factor beta (TGF-ß), which regulates not only inflammation and extracellular matrix formation but also revascularization. This present work aimed at characterizing wound tissues obtained from acute and chronic wounds regarding angiogenesis, inflammation, as well as ECM formation and degradation, to identify common disturbances in the healing process. Serum and wound tissues from 38 patients (N = 20 acute and N = 18 chronic wounds) were analyzed. The patients' sera suggested a shift from VEGF/VEGFR to ANGPT/TIE2 signaling in the chronic wounds. However, this shift was not confirmed in the wound tissues. Instead, the chronic wound tissues showed increased levels of MMP9, a known activator of TGF-ß. However, regulation of TGF-ß target genes, such as CTGF, COL1A1, or IL-6, was absent in the chronic wounds. In wound tissues, all three TGF-ß isoforms were expressed with increased levels of TGF-ß1 and TGF-ß3 and a reporter assay confirmed that the expressed TGF-ß was activated. However, Western blots and immunostaining showed decreased canonical TGF-ß signaling in the respective chronic wound tissues, suggesting the presence of a TGF-ß inhibitor. As a potential regulatory mechanism, the TGF-ß proteome profiler array suggested elevated levels of the TGF-ß pseudo-receptor BAMBI. Also, tissue expression of BAMBI was significantly increased not only in chronic wounds (10.6-fold) but also in acute wounds that had become chronic (9.5-fold). In summary, our data indicate a possible regulatory role of BAMBI in the development of chronic wounds. The available few in vivo studies support our findings by postulating a therapeutic potential of BAMBI for controlling scar formation.
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Factor de Crecimiento Transformador beta3 , Factor de Crecimiento Transformador beta , Humanos , Bioensayo , Western Blotting , Inflamación , Proteínas de la MembranaRESUMEN
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.
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Diclofenaco , Fracturas del Fémur , Ratones , Masculino , Femenino , Animales , Diclofenaco/farmacología , Curación de Fractura , Antiinflamatorios no Esteroideos/farmacología , Microtomografía por Rayos X , Callo Óseo/patología , Fracturas del Fémur/diagnóstico por imagen , Fracturas del Fémur/tratamiento farmacológico , Fracturas del Fémur/patología , Fenómenos BiomecánicosRESUMEN
Cement augmentation of sacroiliac (SI) screws in the posterior pelvic ring has been shown to provide greater biomechanical stability in cadaveric studies. Pelvic ring fractures are relatively rare compared to the total number of fractures. Nevertheless, the 1year mortality rate of up to 27% is very high, especially for geriatric pelvic ring fractures and is also largely associated with reduced mobility due to the fracture. The primary goal of treatment is therefore the restoration of patient mobility. This requires the achievement of sufficient stability of the pelvic ring. As osteoporosis is often a causative factor for the pelvic ring fracture, a more stable anchoring of the implants in the osteoporotic bone can be achieved by cement augmentation. This article presents the possibilities of cement augmentation of the pelvic ring and describes the technique of cement-augmented SI screws.
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Fracturas Osteoporóticas , Huesos Pélvicos , Anciano , Fenómenos Biomecánicos , Cementos para Huesos/uso terapéutico , Tornillos Óseos , Humanos , Fracturas Osteoporóticas/cirugía , Huesos Pélvicos/cirugíaRESUMEN
Methods of artificial intelligence (AI) have found applications in many fields of medicine within the last few years. Some disciplines already use these methods regularly within their clinical routine. However, the fields of application are wide and there are still many opportunities to apply these new AI concepts. This review article gives an insight into the history of AI and defines the special terms and fields, such as machine learning (ML), neural networks and deep learning. The classical steps in developing AI models are demonstrated here, as well as the iteration of data rectification and preparation, the training of a model and subsequent validation before transfer into a clinical setting are explained. Currently, musculoskeletal disciplines implement methods of ML and also neural networks, e.g. for identification of fractures or for classifications. Also, predictive models based on risk factor analysis for prevention of complications are being initiated. As non-union in bone is a rare but very complex disease with dramatic socioeconomic impact for the healthcare system, many open questions arise which could be better understood by using methods of AI in the future. New fields of research applying AI models range from predictive models and cost analysis to personalized treatment strategies.
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Medicina , Sistema Musculoesquelético , Inteligencia Artificial , Aprendizaje Automático , Redes Neurales de la ComputaciónRESUMEN
Nonunions after median sternotomy are rare and usually respond well to surgical treatment. Recalcitrant nonunions despite surgical treatment require a comprehensive mechanical and biological treatment strategy to achieve an adequate functional result for the patient. We demonstrate the case of a 4-year recalcitrant atrophic nonunion. Through a surgical approach guided by the criteria of the nonunion scoring system (NUSS) successful healing was achieved. Our strategy as well as the treatment course are presented.