Undergraduate musculoskeletal ultrasound training based on current national guidelines-a prospective controlled study on transferability.

INTRODUCTION: Musculoskeletal ultrasound (MSUS) is integral to routine clinical diagnostics for musculoskeletal and joint disorders. This study aims to establish and validate a sonography course tailored to undergraduate medical students acquiring MSUS-specific skills at a German university. METHODS: A blended learning training concept, comprising 24 instruction sessions of 45 min each, was designed based on the current national guidelines of the German Society for Ultrasound in Medicine (DEGUM). This program was integrated into the clinical phase of the undergraduate students' medical education. The self-perceived improvement in competency and the effectiveness of the course design were evaluated using a a 7-point Likert scale questionnaire. Objective learning success was evaluated via a written test and a "Direct Observation of Practical Skills" practical exam. Control groups included medical students without MSUS training (control group 1) and doctors who had completed DEGUM-certified basic MSUS courses (control group 2). Both control groups completed the written test, while control group 2 also took the practical final exam. The study involved 146 participants: 56 were allocated to the study group, 44 to control group 1, and 46 to control group 2. RESULTS: The study group rated their skills significantly higher after the course (p < 0.01). Participants expressed high satisfaction with the course design, the teaching materials, and the teachers. The study group's performance on the final written test was comparable to those of control group 2 (p = 0.06) and significantly superior to control group 1 (p < 0.001). Additionally, the study group's performance on the practical final exam was not significantly different from control group 2 (p = 0.28), with both groups achieving scores exceeding 80%. CONCLUSION: Both subjective and objective measures of learning suggest that an MSUS course designed for postgraduates can be effectively adapted for undergraduate medical students. Incorporating MSUS training into the clinical curriculum is recommended to enhance future medical professionals' educational experience and practical skills.

Differences in gait analysis and clinical outcome after dynamic fixation or screw fixation in acute syndesmosis tear: a prospective randomized pilot study.

INTRODUCTION: Acute syndesmosis tears can be treated by static screw or dynamic fixation. Various studies have compared these techniques regarding postoperative outcome. However, to our knowledge, no study has used 3D-instrumented gait analysis (IGA). We hypothesized that a dynamic fixation would perform non-inferior to screw fixation in terms of biomechanical and clinical outcomes. MATERIALS AND METHODS: Patients were prospectively randomized to both groups. All patients received the same follow-up rehabilitation and consultations (6 and 12 weeks; 6 and 12 months) postoperatively. Standardized questionnaires were used to objectify pain and ankle function. At 6 months follow-up, IGA was conducted additionally to objectify the biomechanical outcome. RESULTS: Twenty-five patients in the dynamic fixation (DF) group using TightRope® and twenty-five in the screw fixation group (SF) completed gait analysis. The DF group showed significantly higher mean values for maximum moment in the affected ankle joint (DF: 1.40 ± 0.21 Nm, SF: 1.23 ± 0.30 Nm; p = 0.023) and the unaffected ankle joint (DF: 1.52 ± 0.20 Nm, SF: 1.37 ± 0.27 Nm; p = 0.035). The difference between the affected and unaffected ankle joint was significantly higher in the SF group for active plantarflexion (DF: 1.52 ± 0.20°, SF: 1.37 ± 0.27°; p = 0.035). Both dynamic and screw fixation groups exhibited significantly reduced plantarflexion during the push-off and early swing phase, with moments and powers in the ankle joint also significantly impaired. CONCLUSIONS: Our study demonstrated that dynamic fixation has better or similar biomechanical and clinical outcomes compared to screw fixation. Future research should focus on biomechanical differences during gait as well as clinical outcomes in case of earlier weight-bearing after dynamic fixation. TRIAL REGISTRATION NUMBER (TRN): DRKS00013562 Date of Registration: 07/12/2017.

Earlier consolidation and improved knee function of medial open wedge high tibial osteotomy with autologous bone graft.

PURPOSE: Medial knee osteoarthritis can be treated with medial open wedge high tibial osteotomy (OWHTO). We sought to investigate osseous consolidation of the osteotomy with and without autologous bone grafts (ABG) to detect possible benefits of ABG in osseous healing and functional outcome. METHODS: In this prospective study, patients without graft transplantation were compared to those receiving ABG after medial OWHTO. They were followed up 6 weeks, 12 weeks, 6 months and 12 months postoperatively. Radiographic progress of consolidation, clinical scores, contrast-enhanced ultrasound (CEUS) and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) were assessed at each appointment. RESULTS: A total of 35 patients were enrolled, 20 without and 15 with graft transplantation. Radiologic evaluation showed a significantly earlier consolidation of the osteotomy gaps (p = 0.012) in patients with ABG, resulting in a significantly higher rate of consolidation 12 months after surgery (60% without bone graft vs. 100% with bone graft, p = 0.006). At 6 weeks as well as 6-month follow-up, a tendency of earlier consolidation with ABG was apparent, but not statistically significant (6 weeks: 50% vs. 80%, p = 0.089; 6 months: 30% vs. 60%, p = 0.097). CEUS and DCE-MRI showed physiological perfusion of the osteotomy gaps in both groups. A tendency to better function and less pain in patients with ABG was recognizable. CONCLUSION: In our study, autologous bone grafting evocated earlier osseous consolidation after medial OWHTO and showed a tendency to a better functional outcome.

99mTc-HDP Labeling-A Non-Destructive Method for Real-Time Surveillance of the Osteogenic Differentiation Potential of hMSC during Ongoing Cell Cultures.

99-Metastabil Technetium (99mTc) is a radiopharmaceutical widely used in skeletal scintigraphy. Recent publications show it can also be used to determine the osteogenic potential of human mesenchymal stem cells (hMSCs) by binding to hydroxyapatite formed during bone tissue engineering. This field lacks non-destructive methods to track live osteogenic differentiation of hMSCs. However, no data about the uptake kinetics of 99mTc and its effect on osteogenesis of hMSCs have been published yet. We therefore evaluated the saturation time of 99mTc by incubating hMSC cultures for different periods, and the saturation concentration by using different amounts of 99mTc activity for incubation. The influence of 99mTc on osteogenic potential of hMSCs was then evaluated by labeling a continuous hMSC culture three times over the course of 3 weeks, and comparing the findings to cultures labeled once. Our findings show that 99mTc saturation time is less than 0.25 h, and saturation concentration is between 750 and 1000 MBq. Repeated exposure to γ-radiation emitted by 99mTc had no negative effects on hMSC cultures. These new insights can be used to make this highly promising method broadly available to support researchers in the field of bone tissue engineering using this method to track and evaluate, in real-time, the osteogenic differentiation of hMSC, without any negative influence on the cell viability, or their osteogenic differentiation potential.

Evidence-based uncertainty: do implant-related properties of titanium reduce the susceptibility to perioperative infections in clinical fracture management? A systematic review.

BACKGROUND: Implant-associated infections (IAI) remain a challenging complication in osteosynthesis. There is no consensus or clear evidence whether titanium offers a relevant clinical benefit over stainless steel. PURPOSE: In this systematic review, we sought to determine whether the implant properties of titanium reduce the susceptibility to IAI compared to stainless steel in fracture management. METHODS: A systematic literature search in German and English was performed using specific search terms and limits. Studies published between 1995 and 1st June 2020 in the Cochrane library, MEDLINE and Web of Science databases were included. Only clinical studies comparing titanium and stainless steel implants regarding the susceptibility to infections were selected for detailed review. RESULTS: Five studies out of 384 papers were identified and reviewed. From the studies meeting inclusion criteria one study was a systematic review, two studies were randomized controlled studies (RCT) and two studies were of retrospective comparative nature of level IV evidence. CONCLUSION: Our results show that currently, no proven advantage for titanium implants in respect to IAI can be seen in contemporary literature. Implants preserving periosteal blood-flow and minimising soft-tissue trauma show statistically significant benefits in reducing the incidence of IAI. Clinical studies providing reliable evidence regarding the influence of titanium implants on IAI and investigating the susceptibility of titanium to infection are necessary.

Posttraumatic Perfusion Analysis of Quadriceps, Patellar, and Achilles Tendon Regeneration With Dynamic Contrast-Enhanced Ultrasound and Dynamic Contrast-Enhanced Magnetic Resonance Imaging: Preliminary Results.

OBJECTIVES: The healing process of tendons after surgical treatment of tendon ruptures mainly depends on the perfusion of the tendon and its surrounding tissue. Dynamic contrast-enhanced ultrasound (DCE-US) and dynamic contrast-enhanced MRI (DCE-MRI) can provide additional information about the local microperfusion. In this pilot study, the feasibility of these techniques to assess the vascularization during tendon regeneration was evaluated. METHODS: Between 2013 and 2015, 23 patients with surgical treatment of traumatic rupture of quadriceps, patellar, and Achilles tendons were involved. All patients received clinical follow-up examinations at 6, 12, and at least 52 weeks postoperatively. Dynamic contrast-enhanced US and DCE-MRI examinations were performed 6 and 12 weeks postoperatively. Dynamic contrast-enhanced US perfusion was quantified by the parameters peak enhancement, wash-in area under the curve, rise time, and initial area under the curve. Correlations between these parameters were examined via the Spearman rank correlation. The clinical and functional outcomes were assessed via the Lysholm Knee Score and Knee and Osteoarthritis Outcome Score at 12 and 52 weeks postoperatively. RESULTS: Fourteen patients with quadriceps (n = 8), patellar (n = 4) and Achilles (n = 2) tendon ruptures with complete follow-up were available. The microperfusion could be successful assessed. We could detect a strong correlation of DCE-US (peak enhancement) parameters with DCE-MRI (initial area under the curve) parameters after 6 and 12 weeks. CONCLUSIONS: In this pilot study, DCE-US was able to visualize the microperfusion of healing tendons with a strong correlation with DCE-MRI. Our initial results are in favor of DCE-US as a potential quantitative imaging tool for evaluating the vascularization in tendon regeneration as a complementary method.

A new sequential animal model for infection-related non-unions with segmental bone defect.

BACKGROUND: The treatment of fracture-related infections (FRI) is still a challenge for orthopedic surgeons. The prevalence of FRI is particularly high in open fractures with extensive soft-tissue damage. This study aimed to develop a new two-step animal model for non-unions with segmental bone defects, which could be used to evaluate new innovative bone substitutes to improve the therapeutic options in humans with FRI and bone defects. METHODS: After randomization to infected or non-infected groups, 30 Sprague-Dawley rats underwent a transverse osteotomy of the mid-shaft femur with a 5 mm defect. Additionally, the periosteum at the fracture zone was cauterized at both sides. After intramedullary inoculation with 103 CFU Staphylococcus aureus (infected group) or PBS (non-infected group), a fracture stabilization was done by intramedullary K-wires. After 5 weeks, the bone healing process was evaluated, and revision surgery was performed in order to obtain increased bone healing. The initial K-wires were removed, and debridement of the osteotomy-gap was done followed by a more stable re-osteosynthesis with an angle-stable plate. After further 8 weeks all rats were euthanized and the bone consolidation was tested biomechanically and the callus formation quantitatively by micro-CT analysis. RESULTS: We developed and presented a new two-stage non-union animal model through a targeted S. aureus infection. After 5 weeks, all animals showed a non-union irrespective of assignment to the infected and non-infected group. Lane and Sandhu score showed a higher callus formation in the infected group. In all infected animals, the inoculated S. aureus strain was detected in the revision surgery. The second surgery did not improve bone healing, as shown by the Lane Sandhu score and in the µ-CT analysis. Similarly, biomechanical testing showed in both groups a significantly lower maximum torque as compared to the contralateral side (p < 0.0001). CONCLUSIONS: We were able to successfully develop a new two-stage non-union animal model, which reflects a genuine clinical situation of an infection-related non-union model with segmental bone defects. This model could be used to evaluate various therapeutic anti-infectious and osteoinductive strategies in FRIs.

Contrast-Enhanced Ultrasound (CEUS) Identifies Perfusion Differences Between Tibial Fracture Unions and Non-Unions.

PURPOSE: To assess the value of CEUS in the evaluation of tibial fracture perfusion and its ability to differentiate between physiologic and abnormal fracture healing. MATERIALS AND METHODS: From 2014 to 2017, 107 patients with tibial fractures or tibial non-unions underwent CEUS examination. CEUS was performed at the regular follow-up examination 26 weeks after osteosynthesis or before non-union surgery. Time-intensity curves (TICs) of the contrast enhancement in the fracture gap were generated, and volume parameters such as wash-in rate (WiR), peak enhancement (PE) and wash-in perfusion index (WiPI) were quantified. RESULTS: A total of 34 patients met the inclusion criteria of this study, including 14 consolidated fractures, 12 aseptic non-unions and 8 infected non-unions. WiR, PE and WiPI showed significantly lower values in aseptic non-unions compared to unions (p = 0.009, 0.009, 0.012, resp.). In contrast, infected non-unions showed higher values of WiR, PE and WiPI when compared to unions (p = 0.034, 0.056, 0.029, resp.). CONCLUSION: CEUS represents a feasible method in the assessment of tibial fracture perfusion. Perfusion differences between aseptic and infected tibial non-unions as well as healing tibial fractures could be detected. The deviation of physiologic fracture perfusion seems to be associated with disturbed osseous regeneration leading to non-union.

Preoperative deltoid assessment by contrast-enhanced ultrasound (CEUS) as predictor for shoulder function after reverse shoulder arthroplasty: a prospective pilot study.

INTRODUCTION: Although the deltoid represents the main motor muscle after reverse shoulder arthroplasty (RSA), its standardized preoperative assessment regarding morphology and function is still not established. Its clinical relevance and interactions with major biomechanical parameters like the medialization of the center of rotation (COR) regarding shoulder function after RSA are yet unknown. We evaluated contrast-enhanced ultrasound (CEUS) of the deltoid as possible surrogate marker for individual deltoid properties of patients receiving an RSA, and its predictive value for postoperative shoulder function. MATERIALS AND METHODS: 35 patients were prospectively assessed. Before and 6 months after RSA, dynamic deltoid perfusion, caliber and a combination of both (PE*caliber, named DeltoidEfficacy) was quantified by CEUS. Changes of deltoid properties and the predictive value of preoperative CEUS-based deltoid properties for shoulder function after RSA were assessed. To analyze interrelating effects with deltoid properties, COR-medialization and deltoid lengthening were quantified. RESULTS: Deltoid caliber and perfusion significantly increased after RSA (p = 0.0004/p = 0.002). Preoperative deltoid caliber, perfusion and the combined value DeltoidEfficacy significantly correlated with shoulder function after RSA within the whole study cohort (caliber: r = 0.445, p = 0.009; perfusion: r = 0.593, p = 0.001; DeltoidEfficacy: r = 0.66; p = 0.0002). The predictive value of DeltoidEfficacy for shoulder function after RSA varied among patient subgroups: Multivariate regression analysis revealed the strongest prediction in patients with either very high or very low deltoid properties (Beta = 0.872, r = 0.84, p = 0.0004), independent from COR-medialization or deltoid lengthening. Contrary, in patients with intermediate deltoid properties, COR-medialization revealed the strongest predictive value for shoulder function after RSA (Beta = 0.660, r = 0.597; p = 0.024). CONCLUSION: Deltoid CEUS seems to allow an assessment of individual deltoid properties and deltoid adaptations after RSA. Deltoid CEUS seems to predict shoulder function after RSA and might support an identification of patients requiring special attention regarding COR positioning.

[Diamond concept for treatment of nonunions and bone defects]. / Diamond-Konzept zur Behandlung von Pseudarthrosen und Knochendefekten.

Nonunions represent a very heterogeneous, rare and sometimes very complex disease picture. The causes, localization and degree of expression show a very high variability, which makes it difficult to establish uniform treatment standards. Nevertheless, the process of bone healing is subject to some essential factors, which should be ensured for a successful treatment. Over the years these factors have been better researched and were taken into consideration for the diamond concept, which was first published by Giannoudis et al. in 2007. This provides the physician with a concept that does not neglect the heterogeneity of the disease picture and is an aid to decision making for the treatment regimen in individual cases in order to guarantee the best biological and mechanical conditions. The diamond concept is nowadays widely used and many studies have already demonstrated a successful application. It must be understood as a framework, in which the various treatment options available (bone substitute materials, mesenchymal stem cells, osteosynthesis procedures etc.) are incorporated into the individual factors and therefore provides the physician with a certain freedom of choice in the selection of tools. Additionally, it is not a rigid corset and subject to medical scientific progress in its factors, so that it is exciting to see which new developments will be incorporated in the future.

Correction to: Development and validation of an objective assessment scale for chest tube insertion under 'direct' and 'indirect' rating.

Following publication of the original article [1], the author reported that the given name and family name of all authors were swapped.

Supplementation with 45S5 Bioactive Glass Reduces In Vivo Resorption of the ß-Tricalcium-Phosphate-Based Bone Substitute Material Vitoss.

Compared to other materials such as 45S5 bioactive glass (BG), ß-tricalcium phosphate (ß-TCP)-based bone substitutes such as Vitoss show limited material-driven stimulation of osteogenesis and/or angiogenesis. The unfavorable degradation kinetics of ß-TCP-based bone substitutes may result in an imbalance between resorption and osseous regeneration. Composite materials like Vitoss BA (Vitoss supplemented with 20 wt % 45S5-BG particles) might help to overcome these limitations. However, the influence of BG particles in Vitoss BA compared to unsupplemented Vitoss on osteogenesis, resorption behavior, and angiogenesis is not yet described. In this study, Vitoss and Vitoss BA scaffolds were seeded with human mesenchymal stromal cells before subcutaneous implantation in immunodeficient mice for 10 weeks. Scaffold resorption was monitored by micro-computed tomography, while osteoid formation and vascularization were assessed by histomorphometry and gene expression analysis. Whilst slightly more osteoid and improved angiogenesis were found in Vitoss BA, maturation of the osteoid was more advanced in Vitoss scaffolds. The volume of Vitoss implants decreased significantly, combined with a significantly increased presence of resorbing cells, whilst the volume remained stable in Vitoss BA scaffolds. Future studies should evaluate the interaction of 45S5-BG with resorbing cells and bone precursor cells in greater detail to improve the understanding and application of ß-TCP/45S5-BG composite bone substitute materials.

Bone morphogenetic proteins - 7 and - 2 in the treatment of delayed osseous union secondary to bacterial osteitis in a rat model.

BACKGROUND: Bone infections due to trauma and subsequent delayed or impaired fracture healing represent a great challenge in orthopedics and trauma surgery. The prevalence of such bacterial infection-related types of delayed non-union is high in complex fractures, particularly in open fractures with additional extensive soft-tissue damage. The aim of this study was to establish a rat model of delayed osseous union secondary to bacterial osteitis and investigate the impact of rhBMP-7 and rhBMP-2 on fracture healing in the situation of an ongoing infection. METHODS: After randomization to four groups 72 Sprague-Dawley rats underwent a transverse fracture of the midshaft tibia stabilized by intramedullary titanium K-wires. Three groups received an intramedullary inoculation with Staphylococcus aureus (103 colony-forming units) before stabilization and the group without bacteria inoculation served as healing control. After 5 weeks, a second surgery was performed with irrigation of the medullary canal and local rhBMP-7 and rhBMP-2 treatment whereas control group and infected control group received sterile saline. After further 5 weeks rats were sacrificed and underwent biomechanical testing to assess the mechanical stability of the fractured bone. Additional micro-CT analysis, histological, and histomorphometric analysis were done to evaluate bone consolidation or delayed union, respectively, and to quantify callus formation and the mineralized area of the callus. RESULTS: Biomechanical testing showed a significantly higher fracture torque in the non-infected control group and the infected rhBMP-7- and rhBMP-2 group compared with the infected control group (p < 0.001). RhBMP-7 and rhBMP-2 groups did not show statistically significant differences (p = 0.57). Histological findings supported improved bone-healing after rhBMP treatment but quantitative micro-CT and histomorphometric results still showed significantly more hypertrophic callus tissue in all three infected groups compared to the non-infected group. Results from a semiquantitative bone-healing-score revealed best bone-healing in the non-infected control group. The expected chronic infection was confirmed in all infected groups. CONCLUSIONS: In delayed bone healing secondary to infection rhBMP treatment promotes bone healing with no significant differences in the healing efficacy of rhBMP-2 and rhBMP-7 being noted. Further new therapeutic bone substitutes should be analyzed with the present rat model for delayed osseous union secondary to bacterial osteitis.

Evaluation of App-Based Serious Gaming as a Training Method in Teaching Chest Tube Insertion to Medical Students: Randomized Controlled Trial.

BACKGROUND: The insertion of a chest tube should be as quick and accurate as possible to maximize the benefit and minimize possible complications for the patient. Therefore, comprehensive training and assessment before an emergency situation are essential for proficiency in chest tube insertion. Serious games have become more prevalent in surgical training because they enable students to study and train a procedure independently, and errors made have no effect on patients. However, up-to-date evidence regarding the effect of serious games on performance in procedures in emergency medicine remains scarce. OBJECTIVE: The aim of this study was to investigate the serious gaming approach in teaching medical students an emergency procedure (chest tube insertion) using the app Touch Surgery and a modified objective structural assessment of technical skills (OSATS). METHODS: In a prospective, rater-blinded, randomized controlled trial, medical students were randomized into two groups: intervention group or control group. Touch Surgery has been established as an innovative and cost-free app for mobile devices. The fully automatic software enables users to train medical procedures and afterwards self-assess their training effort. The module chest tube insertion teaches each key step in the insertion of a chest tube and enables users the meticulous application of a chest tube. In contrast, the module "Thoracocentesis" discusses a basic thoracocentesis. All students attended a lecture regarding chest tube insertion (regular curriculum) and afterwards received a Touch Surgery training lesson: intervention group used the module chest tube insertion and the control group used Thoracocentesis as control training. Participants' performance in chest tube insertion on a porcine model was rated on-site via blinded face-to-face rating and via video recordings using a modified OSATS tool. Afterwards, every participant received an individual questionnaire for self-evaluation. Here, trainees gave information about their individual training level, as well as previous experiences, gender, and hobbies. Primary end point was operative performance during chest tube insertion by direct observance. RESULTS: A total of 183 students enrolled, 116 students participated (63.4%), and 21 were excluded because of previous experiences in chest tube insertion. Students were randomized to the intervention group (49/95, 52%) and control group (46/95, 48%). The intervention group performed significantly better than the control group (Intervention group: 38.0 [I50=7.0] points; control group: 30.5 [I50=8.0] points; P<.001). The intervention group showed significantly improved economy of time and motion (P=.004), needed significantly less help (P<.001), and was more confident in handling of instruments (P<.001) than the control group. CONCLUSIONS: The results from this study show that serious games are a valid and effective tool in education of operative performance in chest tube insertion. We believe that serious games should be implemented in the surgical curriculum, as well as residency programs, in addition to traditional learning methods. TRIAL REGISTRATION: German Clinical Trials Register (DRKS) DRKS00009994; https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00009994 (Archived by Webcite at http://www.webcitation.org/6ytWF1CWg).

Development and validation of an objective assessment scale for chest tube insertion under 'direct' and 'indirect' rating.

BACKGROUND: There is an increasing need for objective and validated educational concepts. This holds especially true for surgical procedures like chest tube insertion (CTI). Thus, we developed an instrument for objectification of learning successes: the assessment scale based on Objective Structured Assessment of Technical Skill (OSATS) for chest tube insertion, which is evaluated in this study. Primary endpoint was the evaluation of intermethod reliability (IM). Secondary endpoints are 'indirect' interrater reliability (IR) and construct validity of the scale (CV). METHODS: Every participant (N = 59) performed a CTI on a porcine thorax. Participants received three ratings (one 'direct' on site, two 'indirect' via video rating). IM compares 'direct' with 'indirect' ratings. IR was assessed between 'indirect' ratings. CV was investigated by subgroup analysis based on prior experience in CTI for 'direct' and 'indirect' rating. RESULTS: We included 59 medical students to our study. IM showed moderate conformity ('direct' vs. 'indirect 1' ICC = 0.735, 95% CI: 0.554-0.843; 'direct' vs. 'indirect 2' ICC = 0.722, 95% CI 0.533-0.835) and good conformity between 'direct' vs. 'average indirect' rating (ICC = 0.764, 95% CI: 0.6-0.86). IR showed good conformity (ICC = 0.84, 95% CI: 0.707-0.91). CV was proven between subgroups in 'direct' (p = 0.037) and 'indirect' rating (p = 0.013). CONCLUSION: Results for IM suggest equivalence for 'direct' and 'indirect' ratings, while both IR and CV was demonstrated in both rating methods. Thus, the assessment scale seems a reliable method for rating trainees' performances 'directly' as well as 'indirectly'. It may help to objectify and facilitate the assessment of training of chest tube insertion.

Insulin-Like Growth Factor-1 as a Possible Alternative to Bone Morphogenetic Protein-7 to Induce Osteogenic Differentiation of Human Mesenchymal Stem Cells in Vitro.

Growth factors and mesenchymal stem cells (MSC) support consolidation of bone defects. Bone Morphogenetic Protein-7 (BMP-7) has been used clinically and experimentally, but the outcomes remain controversial. Increased systemic expression of Insulin-like Growth Factor-1 (IGF-1) significantly correlates with successful regeneration of bone healing disorders, making IGF-1 a promising alternative to BMP-7. There is no experimental data comparing the osteoinductive potential of IGF-1 and BMP-7. Therefore, in this study, the influence of IGF-1 and BMP-7 in different concentrations on the osteogenic differentiation of two human MSC-subtypes, isolated from reaming debris (RMSC) and iliac crest bone marrow (BMSC) has been assessed. A more sensitive reaction of BMSC towards stimulation with IGF-1 in concentrations of 400⁻800 ng/mL was found, leading to a significantly higher degree of osteogenic differentiation compared to stimulation with BMP-7. RMSC react more sensitively to stimulation with BMP-7 compared to BMSC. Lower concentrations of IGF-1 were necessary to significantly increase osteogenic differentiation of RMSC and BMSC compared to BMP-7. Therefore, IGF-1 should be considered as a valuable option to improve osteogenic differentiation of MSC and merits further experimental consideration. The MSC subtype and method of differentiation factor application also have to be considered, as they affect the outcome of osteogenic differentiation.

Continuous stimulation with differentiation factors is necessary to enhance osteogenic differentiation of human mesenchymal stem cells in-vitro.

Bone defect treatment belongs to the most challenging fields in orthopedic surgery and requires the well-coordinated application of mesenchymal stem cells (MSC) and differentiation factors. MSC isolated from reaming material (RMSC) and iliac crest (BMSC) in combination with bone morphogenetic protein-7 (BMP-7) and insulin-like growth factor-1 (IGF-1) have been used. The short half-life of both factors limit their applications: a burst release of the factor can probably not induce sustainable differentiation. We stimulated MSC in osteogenic differentiation medium with three different concentrations of BMP-7 or IGF-1: Group A was stimulated continuously, group B for 24 h and group C remained without any stimulation. Osteogenic differentiation was measured after seven and 14 days by alizarin red staining and alkaline phosphatase (ALP) activity. Continuous stimulation led to higher levels of osteogenic differentiation than short-term stimulation. This could lead to a reconsideration of established application forms for differentiation factors, aiming to provide a more sustained release.

Dynamic contrast-enhanced ultrasound and elastography assess deltoid muscle integrity after reverse shoulder arthroplasty.

BACKGROUND: The outcome after reverse shoulder arthroplasty (RSA) depends on the condition of the deltoid muscle, which we assessed with new ultrasound modalities and electromyography (EMG). Contrast-enhanced ultrasound (CEUS) and acoustic radiation force impulse (ARFI) were applied to assess perfusion and elasticity of the deltoid muscle compared with the clinical and functional outcome. METHODS: The study recruited 64 patients (mean age, 72.9 years) treated with RSA between 2004 and 2013. The deltoid muscle was examined with EMG and ultrasound imaging. Functional scores such as Constant score and American Shoulder and Elbow Surgeons Standardized Shoulder Assessment Form score were assessed. Among other CEUS parameters, the wash-in perfusion index, time to peak, and rise time were compared between the operated-on and contralateral shoulders as well as between patients with above-average and below-average outcome. The stiffness of the deltoid muscle was analyzed with ARFI. RESULTS: After RSA, deltoid perfusion (wash-in perfusion index, Δ = -12% ± 22%, P = .0001) and shoulder function (Constant score, Δ = -14 ± 24, P < .0001) were both inferior compared with the contralateral side. This perfusion deficit was associated with a limited range of motion (time to peak and anteversion: r = -0.290, P = .022). Deltoid perfusion was higher in patients with above-average outcome (rise time, Δ = 33% ± 13%, P = .038). The operated-on deltoid muscles showed higher stiffness than the contralateral muscles (ARFI, Δ = 0.2 ± 0.9 m/s, P = .0545). EMG excluded functionally relevant axillary nerve injuries in the study population. CONCLUSIONS: CEUS revealed reduced mean perfusion of the deltoid muscle after RSA. Reduced perfusion was associated with limited range of motion and below-average outcome. Functional shoulder impairment after RSA might be predicted by noninvasive CEUS as a surrogate parameter for the integrity of the deltoid muscle.

A Pronounced Inflammatory Activity Characterizes the Early Fracture Healing Phase in Immunologically Restricted Patients.

Immunologically restricted patients such as those with autoimmune diseases or malignancies often suffer from delayed or insufficient fracture healing. In human fracture hematomas and the surrounding bone marrow obtained from immunologically restricted patients, we analyzed the initial inflammatory phase on cellular and humoral level via flow cytometry and multiplex suspension array. Compared with controls, we demonstrated higher numbers of immune cells like monocytes/macrophages, natural killer T (NKT) cells, and activated T helper cells within the fracture hematomas and/or the surrounding bone marrow. Also, several pro-inflammatory cytokines such as Interleukin (IL)-6 and Tumor necrosis factor α (TNFα), chemokines (e.g., Eotaxin and RANTES), pro-angiogenic factors (e.g., IL-8 and Macrophage migration inhibitory factor: MIF), and regulatory cytokines (e.g., IL-10) were found at higher levels within the fracture hematomas and/or the surrounding bone marrow of immunologically restricted patients when compared to controls. We conclude here that the inflammatory activity on cellular and humoral levels at fracture sites of immunologically restricted patients considerably exceeds that of control patients. The initial inflammatory phase profoundly differs between these patient groups and is probably one of the reasons for prolonged or insufficient fracture healing often occurring within immunologically restricted patients.

[Susceptibility to infections and behavior of stainless steel : Comparison with titanium implants in traumatology]. / Infektanfälligkeit und Verhalten von Stahl : Vergleich mit Titanimplantaten in der Traumatologie.

BACKGROUND: Despite modern treatment options, implant-associated infections (IAI) remain a severe and challenging complication in the treatment of trauma patients. Almost 30 years after the introduction of implants made of titanium alloy into the treatment of trauma patients, there is still no uniform consensus regarding the clinical benefit of titanium alloy in the context of patients with IAI. OBJECTIVE: We sought to determine if implants made of titanium alloy have been proven to be less susceptible regarding IAI in contrast to implants made of stainless steel. MATERIAL AND METHODS: A review of the current literature on IAI in association with the utilized implant material was conducted. Relevant articles from the years 1995 to 2016 were searched in the PubMed database. A total of 183 articles were identified and all abstracts were reviewed for relevance. A total of 14 articles met the inclusion criteria and were stratified according to the level of evidence and furthermore evaluated regarding the influence of the implant material on IAI. RESULTS AND DISCUSSION: Considerable debate remains concerning the influence of the implant material on the susceptibility to IAI; however, the available literature shows that despite slight tendencies, there is no proof of titanium alloy being favorable in the susceptibility to IAI. Furthermore, the literature shows that the design of plates for osteosynthesis might influence IAI. In particular, plates that cause less soft tissue damage and preserve perfusion of the periosteum proved to be beneficial regarding IAI.