Shoulder and Knee Arthroscopy Access Point: Prospective Comparison of Sonographic and Palpatory Detection - Which Method is Better for Novices?

Purpose Arthroscopy is one of the most common interventions in orthopedics. Hence it is important to train users early in order to ensure the safest possible identification of access portals (AP). This prospective study aimed to compare a palpatory (PalpMethod) with a sonographic (SonoMethod) method for AP location in the shoulder and knee joints. Materials and Methods The study included trainee doctors (n=68) attending workshops (lasting approx. 90 minutes). In these workshops a teaching video initially demonstrated the PalpMethod and SonoMethod of AP identification. An experienced operator first marked the access portals on the test subject with a UV pen (determined ideal point [DIP]). Adhesive film was then affixed to the puncture regions. Subsequently participants marked on shoulders and knees first the point determined by palpation, then the point determined by sonography. Analysis involved DIP visualization with a UV lamp and employed a coordinate system around the central DIP. In addition, participants completed an evaluation before and after the workshop. Results The analysis included 324 measurements (n=163 shoulders and n= 161 knees). The majority of participants had not previously attended any courses on manual examination (87.9%) or musculoskeletal ultrasound (93.9%). Overall, the markings participants made on the shoulder using the SonoMethod were significantly closer to the DIP than those made by the PalpMethod (Palp 18.8mm ± 14.5mm vs. Sono 11.2mm ± 7.2mm; p<0.001). On the knee, however, the markings made by the PalpMethod were significantly closer to the DIP overall (Palp 8.0mm ± 3.2mm vs. Sono 12.8mm ± 5.2mm; p<0.001). Conclusion The results show that the SonoMethod produces more accurate markings on the shoulder, while the PalpMethod is superior for the knee.

Comparison between Ultrasound-Guided and Palpatory Localization of the Dorsal Joint Space of the Shoulder Joint.

AIM OF THE STUDY: Arthroscopy ranks among the frequently performed interventions in orthopedics. The aim of this study was to compare the palpation technique with the ultrasound technique for locating the dorsal glenohumeral joint space (JS) in shoulder joint punctures. MATERIAL AND METHODS: Participants inexperienced in ultrasound examinations were included. Palpatory and ultrasound finding of the joint space by the participants was performed according to current recommendations and was initially demonstrated by an instructional video. The ideal point (IP) was marked under ultrasound visualization by an experienced ultrasound examinator and shoulder-elbow surgeon. Furthermore, a corridor for a safe puncture was defined. The palpatorily determined point (pdP) was marked by the participants and evaluated by means of a coordinate system. The evaluation of the sonographically determined point (sdP) was performed similarly to that of the palpatory procedure. RESULTS: Fifty-four participants were included in the study, and the mean length of work experience was 6.3 years. On average, participants had performed 16.5 punctures of the shoulder joint and 6.8 arthroscopies of the shoulder joint. The mean experience in performing sonographic examinations of the shoulder was 27.6 examinations. A total of 100 shoulder joints were examined (54 left, 46 right shoulders). The mean deviation from the ideal point (IP) for the palpatory approach was 17.1 mm with a maximum deviation of 59.5 mm; for the sonographic technique, the mean deviation was 10.3 mm (max. 30.2 mm). Overall, 22% of pdPs were within the defined corridor, while 42% of sdPs were within the target corridor. The average difference between palpatory and sonographic approaches was 9.0 mm in favor of the sonographic technique (max. 46.5 mm). A significantly greater deviation (p < 0.001) from the IP was observed with the palpatory approach than with the sonographic approach. CONCLUSION: Based on the results, the authors recommend ultrasound imaging of the shoulder joint as well as ultrasound-assisted punctures, especially for inexperienced users. Furthermore, training in ultrasound-assisted interventions should be implemented in future training curricula.

The Modified Ultrasound-Assisted Method: A Study of the Correlation between Magnetic Resonance Imaging and the Ultrasound-Assisted Evaluation of the Critical Shoulder Angle.

BACKGROUND: An increased or decreased critical shoulder angle (CSA) is a known risk factor for osteoarthritis, lesions, and re-ruptures in the rotator cuff. A CSA greater than 35° correlates with degenerative rotator cuff tears, while a CSA of less than 30° correlates with osteoarthritis in the glenohumeral joint. The diagnostic gold standard for its determination is X-ray or MRI. OBJECTIVES: The primary objective of this research was to assess the viability of utilizing sonography imaging as a diagnostic tool to determine the modified critical shoulder angle (mCSA). This study aimed to investigate the feasibility and effectiveness of sonographic techniques in accurately diagnosing CSA compared to MRI. STUDY DESIGN AND METHODS: A cohort study was carried out (level of evidence 3). The CSA (MRI) and the mCSA (ultrasound) were assessed retrospectively by two independent board-certified investigators in 109 patients with shoulder pain by MRI and musculoskeletal sonography. The CSA in the MRI dataset was determined using routine protocols and then compared to the values assessed using the modified sonography-assisted method (mCSA). Both results were analyzed with linear regression to determine a possible correlation. All investigations were performed by a DEGUM (German Society for Medical Ultrasound)-certified specialist in musculoskeletal sonography. RESULTS: A total of 112 patients were included in this study, namely 40 female patients and 72 male patients with a mean age of 54.7 years at the time of the investigation. The mean CSA in MRI was 31.5° ± 3.899, and the mCSA in sonography was 30.1° ± 4.753. The inter- and intraobserver reliability for the CSA was factual with values of 0.993 and 0.967. The inter- and intraobserver reliability for mCSA was factual as well, with values of 0.989 and 0.948. The ANOVA analysis did not reveal a significant difference between the CSA and the mCSA values, and linear regression determined the R2 value to be 0.358 with p < 0.05. CONCLUSIONS: Diagnosing the mCSA using sonography is a safe and valid method. No statistically significant differences between the results in MRI and sonography could be seen. Although this is a retrospective, single-center study including only Caucasian mid-Europeans, and with the known limitations of ultrasound imaging, it nevertheless shows that sonography can be used as a simple, cheap, and fast technique to assess a modified CSA, which shows very good correlation with the standard CSA without losing the diagnostic quality.

Impact of Anti-Mycotic Drugs on the Osteogenic Response of Bone Marrow Mesenchymal Stem Cells In Vitro.

The treatment of fungal bone infections and infected non-unions is a huge challenge in modern trauma and orthopedics, which normally contain the local and systemic administration of anti-fungal drugs. Although frequently used, little is known about the impact of systemic and locally administered fungicides on the osteogenic regenerative capabilities of infected bone tissue, especially upon the osteogenesis of human bone marrow mesenchymal stem cells (BM-hMSCs). This study evaluates the effects of the three most common fungicides for the systemic treatment of bone infections, Voriconazole (VOR), liposomal Amphotericin B (LAMB), and Fluconazole (FLU), as well as the effects of VOR and LAMB-loaded Polymethylmethacrylate (PMMA) cement chips in different concentrations upon the osteogenic response of BM-hMSCs in vitro. Within this study, we compared the ability of BM-hMSC to differentiate into osteoblast-like cells and synthesize hydroxyapatite as assessed by radioactive 99mTechnetium-Hydroxydiphosphonate (99mTc-HDP) labeling, cell proliferation, and analyses of supernatants upon various osteogenic parameters. Our results revealed that VOR added to the cell culture medium affects the osteogenic potential of BM-hMSC negatively, while there were no detectable effects of LAMB and FLU. Moreover, we showed dose-dependent negative effects of high- and extended-dose fungicide-loaded PMMA cement due to cytotoxicity, with a higher cytotoxic potential of VOR than LAMB, while low-dose fungicide-loaded PMMA had no significant effect on the osteogenic potential of BM-hMSC in vitro.

Impact of Antibiotic-Loaded PMMA Spacers on the Osteogenic Potential of hMSCs.

Antibiotic-loaded PMMA bone cement is frequently used in modern trauma and orthopedic surgery. Although many of the antibiotics routinely applied are described to have cytotoxic effects in the literature, clinical experience shows no adverse effects for bone healing. To determine the effects of antibiotic-loaded PMMA spacers on osteogenesis in vitro, we cultivated human bone marrow mesenchymal stem cells (BM-hMSCs) in the presence of PMMA spacers containing Gentamicin, Vancomycin, Gentamicin + Clindamycin as well as Gentamicin + Vancomycin in addition to a blank control (agarose) and PMMA containing no antibiotics. The cell number was assessed with DAPI staining, and the osteogenic potential was evaluated by directly measuring the amount of hydroxyapatite synthesized using radioactive 99mTc-HDP labelling as well as measuring the concentration of calcium and phosphate in the cell culture medium supernatant. The results showed that Gentamicin and Vancomycin as well as their combination show a certain amount of cytotoxicity but no negative effect on osteogenic potential. The combination of Gentamicin and Clindamycin, on the other hand, led to a drastic reduction in both the cell count and the osteogenic potential.

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.

Use of Autologous Bone Graft with Bioactive Glass as a Bone Substitute in the Treatment of Large-Sized Bone Defects of the Femur and Tibia.

BACKGROUND: Managing bone defects in non-union surgery remains challenging, especially in cases of large defects exceeding 5 cm in size. Historically, amputation and compound osteosynthesis with a remaining PMMA spacer have been viable and commonly used options. The risk of non-union after fractures varies between 2% and 30% and is dependent on various factors. Autologous bone grafts from the iliac crest are still considered the gold standard but are limited in availability, prompting consideration of artificial grafts. OBJECTIVES: The aims and objectives of the study are as follows: 1. To evaluate the radiological outcome of e.g., the consolidation and thus the stability of the bone (three out of four consolidated cortices/Lane-Sandhu-score of at least 3) by using S53P4-type bioactive glass (BaG) as a substitute material for large-sized bone defects in combination with autologous bone using the RIA technique. 2. To determine noticeable data-points as a base for future studies. METHODS: In our clinic, 13 patients received bioactive glass (BaG) as a substitute in non-union therapy to promote osteoconductive aspects. BaG is a synthetic material composed of sodium, silicate, calcium, and phosphate. The primary endpoint of our study was to evaluate the radiological consolidation of bone after one and two years. To assess bone stabilization, we used a modified Lane-Sandhu score, considering only radiological criteria. A bone was considered stabilized if it achieved a minimum score of 3. For full consolidation (all four cortices consolidated), a minimum score of 4 was required. Each bone defect exceeded 5 cm in length, with an average size of 6.69 ± 1.92 cm. RESULTS: The mean follow-up period for patients without final bone consolidation was 34.25 months, with a standard deviation of 14.57 months, a median of 32.00 months and a range of 33 months. In contrast, patients with a fully consolidated non-union had an average follow-up of 20.11 ± 15.69 months and a range of 45 months. Overall, the mean time from non-union surgery to consolidation for patients who achieved final union was 14.91 ± 6.70 months. After one year, six patients (46.2%) achieved complete bone consolidation according to the Lane-Sandhu score. Three patients (23.1%) displayed evident callus formation with expected stability, while three patients (23.1%) did not develop any callus, and one patient only formed a minimal callus with no expected stability. After two years, 9 out of 13 patients (69.2%) had a score of 4. The remaining four patients (30.8%) without expected stability either did not heal within two years or required a revision during that time. CONCLUSIONS: Bioactive glass (BaG) in combination with autologous bone (RIA) appears to be a suitable filler material for treating extensive non-unions of the femur and tibia. This approach seems to show non-inferiority to treatment with Tricalcium Phosphate (TCP). To ensure the success of this treatment, it is crucial to validate the procedure through a randomized controlled trial (RCT) with a control group using TCP, which would provide higher statistical power and more reliable results.

Association of Chondrolabral Lesions with Ultrasound-Guided Detection of Pathological Head-Neck Contour.

OBJECTIVE: This study aimed to investigate whether the asphericity of the neck-head junction of the femur confirmed via ultrasound is associated with further pathology due to femoro-acetabular impingement (FAI). METHODOLOGY: After a clinical examination with positive FAI tests, an ultrasound examination of the hip was performed. In the case of asphericity, a quantitative ultrasound-assisted assessment of the hip was performed, followed by contrast-enhanced arthro-MRI with the question of cartilage or labral damage. RESULTS AND CONCLUSIONS: We included 51 patients with a mean age of 35.25. According to the examination algorithm, asphericity was present in all patients via ultrasonography. The average anterior alpha angle (AAA) determined in ultrasonography was 43.49°. The average AAA on the arthro-MRI was 44.19°. The mean anterior head neck offset (AHNO) in ultrasound was 5.27 mm, and in arthro-MRI, it was 5.36 mm. Arthro-MRI confirmed a bump in 47 patients and a talization disorder in 4 patients. In 49 patients, a labral lesion was found, with one being a re-rupture. Furthermore, in one patient, labral degeneration was identified. Cartilage damage to the hip joint was found in 25 patients. Two patients had neither labral nor cartilage damage in the arthro-MRI. In our study, sonographically confirmed asphericity of the head-neck junction was found in 49 cases, which was associated with further pathology and, according to the current doctrine, was attributable to the FAI and required surgical intervention. This study shows that the detection of a pathologic head and neck contour via ultrasound in combination with positive clinical signs, as present in FAI, is associated with chondrolabral lesions detected via arthro-MRI in 96.1% of cases.

Digital Transformation in Musculoskeletal Ultrasound: Acceptability of Blended Learning.

BACKGROUND: ultrasound diagnostics have a broad spectrum of applications, including among diseases of the musculoskeletal system. Accordingly, it is important for the users to have a well-founded and up-to-date education in this dynamic examination method. The right balance between online and in-class teaching still needs to be explored in this context. Certifying institutions are currently testing digitally transformed teaching concepts to provide more evidence. METHODS: this study compared two musculoskeletal ultrasound blended learning models. Model A was more traditional, with a focus on in-person teaching, while Model B was more digitally oriented with compulsory webinar. Both used e-learning for preparation. Participants completed evaluations using a seven-point Likert scale, later converted to a 0-1 scale. Digital teaching media (e-learning) were used for preparation in both courses. RESULTS: the analysis included n = 41 evaluations for Model A and n = 30 for Model B. Model B received a better overall assessment (median: 0.73 vs. 0.69, p = 0.05). Model B also excelled in "course preparation" (p = 0.02), "webinar quality" (p = 0.04), and "course concept" (p = 0.04). The "gain of competence" (p = 0.82), "learning materials" (p = 0.30), and "tutor quality" (p = 0.28) showed no significant differences. CONCLUSION: participants favorably assessed blended learning in ultrasound teaching. Certifying institutions should consider accrediting models that combine digital methods (e.g., internet lectures/webinars) and materials (e.g., e-learning) with hands-on ultrasound training. Further research is needed to validate these subjective findings for a stronger evidential basis.

Matched-Pair Analysis: Large-Sized Defects in Surgery of Lower Limb Nonunions.

BACKGROUND: The treatment of large-sized bone defects remains a major challenge in trauma and orthopaedic surgery. Although there are many treatment options, there is still no clear guidance on surgical management, and the influence of defect size on radiological and clinical outcome remains unclear due to the small number of affected patients. The aim of the present study was to determine the influence of defect size on the outcome of atrophic and infected nonunions of the tibia or the femur based on the diamond concept in order to provide recommendations for treatment guidance. PATIENTS AND METHODS: All medical records, surgical reports, laboratory data and radiological images of patients treated surgically for atrophic or infected nonunions of the lower limbs (femur or tibia) between 1 January 2010 and 31 December 2020 were examined. Patients with proximal, diaphyseal or distal nonunions of the femur or tibia who were surgically treated at our institution according to the "diamond concept" and attended our standardised follow-up program were included in a database. Surgical treatment was performed as a one- or two-step procedure, depending on the type of nonunion. Patients with a segmental bone defect ≥5 cm were matched with patients suffering a bone defect <5 cm based on five established criteria. According to our inclusion and exclusion criteria, 70 patients with a bone defect ≥5 cm were suitable for analysis. Two groups were formed by matching: the study group (bone defect ≥5 cm; n = 39) and control group (bone defect <5 cm; n = 39). The study was approved by the local ethics committee (S-262/2017). RESULTS: The mean defect size was 7.13 cm in the study and 2.09 cm in the control group. The chi-square test showed equal consolidation rates between the groups (SG: 53.8%; CG: 66.7%). However, the Kaplan-Meier curve and log-rank test showed a significant difference regarding the mean duration until consolidation was achieved, with an average of 15.95 months in the study and 9.24 months in the control group (α = 0.05, p = 0.001). Linear regression showed a significant increase in consolidation duration with increasing defect size (R2 = 0.121, p = 0.021). Logistic regression modelling showed a significant negative correlation between consolidation rate and revision performance, as well as an increasing number of revisions, prior surgeries and total number of surgeries performed on the limb. Clinical outcomes showed equal full weight bearing of the lower extremity after 5.54 months in the study vs. 4.86 months in the control group (p = 0.267). CONCLUSION: Surprisingly, defect size does not seem to have a significant effect on the consolidation rate and should not be seen as a risk factor. However, for the treatment of large-sized nonunions, the follow-up period should be prolonged up to 24 months, due to the extended time until consolidation will be achieved. This period should also pass before a premature revision with new bone augmentation is performed. In addition, it should be kept in mind that as the number of previous surgeries and revisions increases, the prospects for consolidation decrease and a change in therapeutic approach may be required.

Effect of Tricalcium Phosphate on Healing of Non-Unions: An Observational Study of over 400 Non-Unions.

Purpose: A central aspect of the treatment of non-unions is the filling of bone defects. The quantity of available autologous bone for this purpose is limited. Alternatively, or additionally, bone substitutes may be used. The aim of this retrospective, single-center study including 404 non-unions in 393 patients is to investigate the effect of tricalcium phosphate (TCP) on the healing of non-unions. Furthermore, the influence of gender, age, smoking status, comorbidities, type of surgical procedure, presence of infection, and length of treatment was investigated. Methods: We evaluated three groups of patients. Group 1 received TCP + BG, group 2 received BG alone and group 3 received no augmentation. Bone stability was assessed 1 and 2 years after non-union revision surgery through analysis of radiographs using the Lane Sandhu Score. Scores ≥3 were rated as stable Other influencing factors were collected from the electronic medical record. Results: In 224 non-unions, bone defects were filled with autologous bone and TCP (TCP+BG). In 137 non-unions, bone defects were filled with autologous bone (BG), and in 43 non-unions presenting non-relevant defects, neither autologous bone nor TCP were used (NBG). After 2 years, 72.7% of the TCP+BG patients, 90.1% of the BG patients and 84.4% of the NBG patients achieved a consolidation score ≥3. Advanced age, presence of comorbidities and longer treatment period had a significantly negative effect on consolidation 1 year after surgery. Longer treatment periods also showed a negative significant effect after 2 years. It is notable that larger defects, mainly treated with the combination of autologous bone and TCP, showed similar healing rates to that of smaller defects after 2 years. Conclusion: The combination of TCP and autologous bone-grafts shows good results in the reconstruction of complicated bone-defects, but patience is required since the healing period exceeds 1 year in most patients.

Functional outcome and CEUS-assessed deltoid muscle vitality after fracture-specific versus standard prosthetic design in reverse shoulder arthroplasty for trauma.

Functional outcome after reverse-shoulder-arthroplasty (RSA) in proximal humerus fractures (PHF) depends on deltoid muscle integrity and successful reattachment of the tuberosities for best possible recovery of rotator-cuff function. In this monocentric, prospective, randomized, controlled trial we investigated whether a reverse-fracture-prosthesis (RFP) with a metaphyseal fenestrated stem achieved superior shoulder and muscle function compared to a common reverse-prosthesis (RP) design for patients with PHF. Our hypothesis was that patients with RFP may achieve a superior healing rate of the greater tuberosity (GT) compared to patients receiving RP, which translates to significantly higher clinical outcome and functional scores as well as differences in deltoid muscle microperfusion. Forty-four patients with PHF were randomized preoperatively to one of the prosthesis types in RSA between 2018 and 2020 (22 with RFP and 22 with RP) and prospectively assessed 6 months after surgery. We assessed osteointegration of the GT with radiographs 1 day and 6 months postoperatively and examined shoulder function and patient satisfaction by using established shoulder scores. A contrast-enhanced ultrasound (CEUS) examination of both shoulders was performed to quantify intramuscular blood flow and evaluate vitality of the deltoid muscle. None of the functional and psychosocial scores or radiographs and ultrasound examinations showed significant differences between the RSA designs. The constant-Murley score (p = 0.384) and active anterior-elevation-abduction, and external rotation were comparable between the RFP and RP group. Similar healing rates of the GT were observed (p = 0.655). CEUS-assessed deltoid microperfusion revealed equivalent muscle vitality for both groups (p = 0.312). Level of evidence: Level II; Randomized Controlled Trial; Treatment Study. Clinical significance: The radiographic evaluation for the investigation of the GT healing rate indicates that the proclaimed benefits of the fracture prosthesis with fenestration design might not be as great as expected.

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.

Efficacy of an Antibiotic Loaded Ceramic-Based Bone Graft Substitute for the Treatment of Infected Non-Unions.

The treatment of non-unions is often complicated by segmental bone defects and bacterial colonization. Because of the limited availability of autologous bone grafts, tissue engineering focuses on antibiotic-loaded bone graft substitutes. HACaS+G is a resorbable calcium sulphate-hydroxyapatite loaded with gentamicin. The osteoinductive, osteoconductive, and anti-infective effect of HACaS+G has already been demonstrated in clinical studies on patients with chronic osteomyelitis. However, especially for the treatment of infected non-unions with segmental bone defects by HACaS+G, reliable clinical testing is difficult and sufficient experimental data are lacking. We used an already established sequential animal model in infected and non-infected rat femora to investigate the osteoinductive, osteoconductive, and anti-infective efficacy of HACaS+G for the treatment of infected non-unions. In biomechanical testing, bone consolidation could not be observed under infected and non-infected conditions. Only a prophylactic effect against infections, but no eradication, could be verified in the microbiological analysis. Using µ-CT scans and histology, osteoinduction was detected in both the infected and non-infected bone, whereas osteoconduction occurred only in the non-infected setting. Our data showed that HACaS+G is osteoinductive, but does not have added benefits in infected non-unions in terms of osteoconduction and mechanical bone stability, especially in those with segmental bone defects.

Treatment of Infection-Related Non-Unions with Bioactive Glass-A Promising Approach or Just Another Method of Dead Space Management?

The treatment of infected and non-infected non-unions remains a major challenge in trauma surgery. Due to the limited availability of autologous bone grafts and the need for local anti-infective treatment, bone substitutes have been the focus of tissue engineering for years. In this context, bioactive glasses are promising, especially regarding their anti-infective potential, which could reduce the need for local and systemic treatment with conventional antibiotics. The aim of this study was to investigate the osteoinductive and osteoconductive effects, as well as the anti-infectious potential, of S53P4 using a standardized non-union model, which had not been investigated previously. Using an already established sequential animal model in infected and non-infected rat femora, we were able to investigate bioactive glass S53P4 under realistic non-union conditions regarding its osteoinductive, osteoconductive and anti-infective potential with the use of µCT scans, biomechanical testing and histological, as well as microbiological, analysis. Although S53P4 did not lead to a stable union in the non-infected or the infected setting, µCT analysis revealed an osteoinductive effect of S53P4 under non-infected conditions, which was diminished under infected conditions. The osteoconductive effect of S53P4 remained almost negligible in histological analysis, even 8 weeks after treatment. Additionally, the expected anti-infective effect could not be demonstrated. Our data suggested that S53P4 should not be used in infected non-unions, especially in those with large bone defects.

Tibial plateau fracture: does fracture classification influence the choice of surgical approach? A retrospective multicenter analysis.

PURPOSE: The role of classification systems for the choice of surgical approach and the management of tibial plateau fractures remains unclear. The purpose of this study was to investigate the potential of classification systems to choose the appropriate operative approach. Current surgical management strategies were investigated in a large multicenter assessment. METHODS: In this study, we retrospectively analyzed all patients with tibial plateau fractures that have received surgical treatment in one of the five Level I trauma facilities between 2012 and 2015. Fractures were classified in each center by a senior orthopedic surgeon using the AO/OTA and the Luo classification. Demographics, trauma mechanism, as well as the surgical approach were recorded. RESULTS: 538 patients (46.1% male, 53.9% female) were included. The anterolateral approach was used most frequently with 54.8% of all single approaches; 76.2% of all combined approaches used anterolateral as part of the approach. Combined approaches were used in 22.5% of the cases; a combination of the anterolateral and medial (10%), anterolateral, and posteromedial approach (5.8%) were used most frequently. The lowest number was found for the posterolateral (1.3%) and the combined approaches dorsal/anterolateral and medial/dorsal (1.7%, 1.1%). The AO/OTA classification showed a peak for 41.B2 (21.9%) and B3 (35.5%) fractures. Regarding the Luo classification, the dorsal column was involved in 45.7%. In contrast, only 14.7% of the surgical approaches used were able to address the dorsal tibial plateau potentially. CONCLUSION: The use of dorsal approach seems to be of minor importance than expected in daily clinical practice in this multicenter study. It was not possible to specify whether the AO/OTA or the Luo classification can reliably predict the choice of surgical approach. The operative treatment strategy of tibial plateau fractures seems to rather rely on the surgeons' experience, education, and preferences.

99mTc-polyphosphonate labelling - Enhancement of a novel method for the quantification of osteogenic differentiation of MSCs in vitro.

Bone tissue engineering is a fast-growing field in regenerative medicine. Consequently, there is a high demand for new, fast and reliable methods to track and quantify the osteogenic differentiation of cells. Recently, a novel method was published to non-destructively quantify the hydroxyapatite content of monolayer and 3-dimensional mesenchymal stem cell cultures using the ability of 99mTechnetium-methylene diphosphonate (MDP), a well-established tracer in clinical nuclear medicine, to bind to newly synthesized hydroxyapatite. In the present study, two other commonly used 99mTechnetium tracers, 2,3-dicarboxypropane-1,1-diphosphonate (DPD) and hydroxydiphosphonate (HDP), were evaluated to see if they could also be used for the same purpose. Furthermore, we investigated if labelling at various timepoints influenced the effectiveness of the labelling. The results were analysed using one-factor ANOVA followed by Bonferroni post-hoc testing. This revealed a highly significant difference between the three osteogenic groups at each timepoint compared to their corresponding negative controls. However, there was no statistically significant difference between the three different tracers (MDP, DPD, HDP) in the osteogenic groups. Therefore all three tracers are of similar value when quantifying the extracellular hydroxylapatite content in osteogenic stem cells cultures.

Preoperative contrast-enhanced ultrasound (CEUS) of long bone nonunions reliably predicts microbiology of tissue culture samples but not of implant-sonication.

INTRODUCTION: Bacterial infection in the context of fracture repair remains a severe complication in trauma surgery and may result in long bone nonunion. Since treatment options for aseptic and infected nonunions vary greatly, diagnostic methods should ideally differentiate between these two entities as accurately as possible. Recently, contrast-enhanced ultrasound (CEUS) has been introduced as a preoperative imaging technique to evaluate hypervascularity at the fracture site as sign of bacterial infection. HYPOTHESIS: Preoperative CEUS predicts results of microbiological evaluation obtained either by culture of tissue samples or by analyzing the sonication fluid following removal and sonication of the implant. PATIENTS AND METHODS: Over the course of 6 months, 26 patients with long bone nonunions were included in this study. Patients' clinical data were evaluated. Tissue samples were collected intraoperatively and examined by standard microbiological techniques. The sonication method was applied to removed implants. Additionally, 1-3 days before surgery, CEUS was performed to determine hypervascularity at the nonunion site as a possible parameter for infection. RESULTS: Culture of tissue samples indicated infection in 50% of cases and implant sonication in 57.7% of cases. However, there was merely a fair agreement (κ=0.231) between these two diagnostic methods. CEUS predicted results of tissue culture reliably (sensitivity 92.3% and specificity 100%), whereas implant sonication showed no significant correlations with results from CEUS. Hypertrophic and atrophic nonunions were evaluated separately to determine possible differences in vascularity. We found that contrast peak enhancement of CEUS was similar in atrophic and hypertrophic nonunions with positive culture of tissue samples. Both differed significantly from culture negative cases (p=0.0016 and 0.0062). Results of implant-sonication positive or negative cases in atrophic and hypertrophic nonunions, however, were less clear and could be misleading. DISCUSSION: We were able to confirm CEUS as a valuable preoperative diagnostic tool that reliably predicts microbiology of tissue culture samples, but not of implant sonication. LEVEL OF EVIDENCE: I; diagnostic study.

Impact of High-Dose Anti-Infective Agents on the Osteogenic Response of Mesenchymal Stem Cells.

Treatment of infected nonunions and severe bone infections is a huge challenge in modern orthopedics. Their treatment routinely includes the use of anti-infective agents. Although frequently used, little is known about their impact on the osteogenesis of mesenchymal stem cells. In a high- and low-dose set-up, this study evaluates the effects of the antibiotics Gentamicin and Vancomycin as well as the antifungal agent Voriconazole on the ability of mesenchymal stem cells to differentiate into osteoblast-like cells and synthesize hydroxyapatite in a monolayer cell culture. The osteogenic activity was assessed by measuring calcium and phosphate concentrations as well as alkaline phosphatase activity and osteocalcin concentration in the cell culture medium supernatant. The amount of hydroxyapatite was measured directly by radioactive 99mTechnetium-HDP labeling. Regarding the osteogenic markers, it could be concluded that the osteogenesis was successful within the groups treated with osteogenic cell culture media. The results revealed that all anti-infective agents have a cytotoxic effect on mesenchymal stem cells, especially in higher concentrations, whereas the measured absolute amount of hydroxyapatite was independent of the anti-infective agent used. Normed to the number of cells it can therefore be concluded that the above-mentioned anti-infective agents actually have a positive effect on osteogenesis while high-dose Gentamycin, in particular, is apparently capable of boosting the deposition of minerals.

Contrast-Enhanced Ultrasound: A Viable Diagnostic Tool in Predicting Treatment Failure after Non-union Revision Surgery for Upper- and Lower-Limb Non-unions.

Non-unions remain a major complication in the treatment of long-bone fractures and affect quality of life considerably. Both early detection and treatment of non-unions are essential to secure subsequent fracture union. Sufficient vascularization plays a key role in the healing process. The aim of this prospective study was to quantify the microperfusion within non-unions by means of contrast-enhanced ultrasound (CEUS) as early as 12 wk after non-union surgery and to examine the prognostic capability of CEUS in predicting treatment failure. Among 112 patients who had undergone non-union surgery, consolidation within 36 mo was achieved in 89 patients ("responders"), whereas 23 patients showed persistent non-unions ("non-responders") and required further surgery. CEUS quantification parameters such as peak enhancement, wash-in area under the curve and wash-in perfusion index revealed significantly higher perfusion levels in "responders" compared with "non-responders" (p < 0.05). Receiver operator characteristic curve analysis revealed that persistent fracture non-unions could be predicted with a sensitivity/specificity of 88.7%/72.2% in lower-limb non-unions and a sensitivity/specificity of 66.7%/100.0% in upper-limb non-unions. CEUS is a suitable diagnostic tool in predicting treatment failure as early as 12 wk after non-union surgery and should be integrated into the clinical routine when deciding on revision surgery at an early stage.