From Benign Lipoma to G3 Liposarcoma: Contrast-Enhanced Ultrasound Reveals Tumor Microperfusion and Indicates Malignancy.

OBJECTIVE: Lipomatous soft tissue tumors (STT), ranging from benign lipomas to malignant liposarcomas, require accurate differentiation for timely treatment. Complementary to MRI, Contrast-enhanced ultrasound (CEUS) is emerging as a promising tool, providing insight into tumor microperfusion in real-time. This study aims to explore the potential of preoperative CEUS in differentiating benign lipomatous tumors from malignant liposarcoma subtypes. METHODS: Eighty-seven patients with lipomatous STT scheduled for surgery were enrolled. Clinical and MRI assessments were conducted to obtain general tumor characteristics. CEUS was used for a standardized tumor perfusion evaluation. Perfusion analysis included peak enhancement, rise time, wash-in perfusion index, and wash-out rate, reflecting the perfusion kinetics. Histopathological results were obtained for every STT and compared to perfusion characteristics. RESULTS: In total, 48 lipoma, 23 ALT and 11 liposarcoma were identified. Significant differences in tumor microperfusion were demonstrated, with higher perfusion levels indicating higher malignancy (Peak enhancement [a.u.] of Lipoma: 145 ± 238; ALT: 268 ± 368; Liposarcoma: 3256 ± 4333; p (ALT vs. Liposarcoma) < 0.001). A perfusion-based identification of a benign lipoma or ALT versus sarcoma resulted in a positive predictive value of 93%. Patient-related factors (age, gender, BMI, ASA score, smoking status) had no significant impact on the CEUS-based perfusion parameters. CONCLUSION: Our study suggests CEUS as a capable non-invasive tool for improving preoperative assessment of lipomatous STT. It can assist in the distinction between benign and malignant STT, accelerating treatment decisions and enhancing patient outcomes. Significant correlations between CEUS-derived parameters and malignancy highlight its risk assessment 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.

Contrast-enhanced ultrasound reveals perfusion differences between benign lipoma and semi-malignant atypical lipomatous tumors: A prospective clinical study.

PURPOSE: Soft tissue tumors (STT) are difficult to diagnose accurately, and distinguishing between benign and malignant tumors is challenging. Lipoma is the most common STT, while atypical lipomatous tumors (ALT) can dedifferentiate into malignant lipomatous tumors like grade 1 liposarcoma and require more radical therapy. This study aims to investigate the potential of contrast-enhanced ultrasound (CEUS) to differentiate between lipoma and ALT based on tumor perfusion. MATERIALS AND METHODS: We prospectively examined 52 patients who were scheduled for biopsy for suspected lipoma or ALT. The CEUS examination was performed using SonoVue as a contrast agent to quantify tumor perfusion using VueBox V7.1 software. Peak enhancement (PE), rise time (RT), wash-in perfusion index (WiPI), and wash-out rate (WoR) were used to assess contrast enhancement inside the STT. RESULTS: Among 50 tumors examined, 30 were lipomas, and 20 were ALTs. We found significant differences in perfusion between lipomas and ALTs (PE: 49.22 ± 45.75 a.u. vs. 165.67 ± 174.80; RT: 23.86 ± 20.47s vs. 10.72 ± 5.34 s; WiPI: 33.06 ± 29.94 dB vs. 107.21 ± 112.43 dB; WoR: 2.44 ± 3.70 dB/s vs. 12.75 ± 15.80 dB/s; p<.001). ROC analysis of PE resulted in a diagnostic accuracy of 74% for the detection of an ALT, and 77% for the detection of a lipoma. CONCLUSION: CEUS may enhance the differential diagnosis of benign lipomas and ALTs, with ALTs showing higher levels of perfusion. If larger prospective studies confirm these findings, CEUS could enhance diagnostic accuracy, guide surgical planning, and potentially reduce unnecessary treatments for patients presenting with ambiguous lipomatous tumors like lipoma or ALT.

Contrast-Enhanced Ultrasound-Assessed Supraspinatus Muscle Perfusion Indicates Better Tissue Vitality and Outcome After Supraspinatus Tendon Repair and Subacromial Decompression.

OBJECTIVE: Supraspinatus tendon (SSP) tears are a frequent indication for shoulder surgery. Therapy options include physiotherapy, tendon repair and less invasive surgical options like subacromial decompression (SAD). The selection of the most appropriate treatment depends on the specific characteristics and needs of each patient subgroup. Typically, physically active patients are candidates for tendon repair, while a conservative approach is preferred for individuals with severe muscle degeneration or low physical demands. The goal of this study was to assess the impact of contrast-enhanced ultrasound (CEUS)-assessed SSP muscle perfusion on post-operative shoulder function and tendon healing in patients undergoing SSP repair or SAD, thereby enhancing personalized therapy for SSP tendon tears. METHODS: Two cohorts of patients with SSP tendon tears were treated either by SAD or tendon repair. Pre-operative and 6-month post-operative SSP muscle perfusion was quantified using CEUS and investigated as a surrogate for tissue vitality. The magnetic resonance imaging-derived parameters fatty infiltration and tendon retraction and established shoulder function scores were assessed pre- and post-operatively. RESULTS: Thirty-five SSP repair patients were compared with 20 SAD patients. Pre-operative perfusion was comparable in the SAD and SSP repair cohorts when a re-tear occurred (wash-in perfusion index = 103.8 ± 124.0 vs. 114.6 ± 155.0, p = 0.83), while being significantly higher among patients with an intact repair (103.8 ± 124 vs. 325.4 ± 388.6, p = 0.006). Below-median pre-operative muscle perfusion was associated with lower post-operative shoulder function (Constant score: 59 ± 28 vs. 78 ± 19, p = 0.012). CONCLUSION: CEUS can visualize SSP muscle perfusion as a surrogate for tissue vitality and tendon healing, which is associated with better post-operative shoulder function.

CEUS-assessed supraspinatus muscle perfusion improves after tendon repair and predicts anatomical and functional outcome: A 1-year prospective pilot study.

Rotator cuff tear including SSP (Supraspinatus) tendon tears are a very common and often painful condition with several therapeutic options such as tendon repair. Reflected by the high retear rates, the preoperative selection of patients suitable for surgery or conservative treatment, which often yields comparable results, remains difficult. Using contrast-enhanced ultrasound (CEUS), it is possible to quantify the SSP muscle perfusion as a surrogate parameter for its vitality and healing capabilities. In this study, we enrolled 20 patients who underwent an SSP repair for a preoperative and two postoperative (6 months and 1 year) clinical and sonographic exams including CEUS. Along with functional improvement (p < 0.001, Constant score), we found a significant increase in CEUS-assessed muscle perfusion after tendon repair (p < 0.001). Furthermore, weak preoperative muscle perfusion was associated with a higher risk of a retear (χ2 = 0.045) and a moderate trend toward lower postoperative shoulder function that did not reach significance (r = 0.435; p = 0.055, DASH score). If confirmed in larger studies, CEUS might be a valuable additional diagnostic method for a precise selection of patients who most likely profit from a tendon repair and those who can be treated conservatively with an equally good outcome.

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.

New perspectives for investigating muscular perfusion response after dietary supplement intake: an exploratory, randomized, double-blind, placebo-controlled crossover trial in healthy young athletes using contrast-enhanced ultrasound (CEUS).

Background: Various dietary supplements have been reported to enhance muscular perfusion in athletes practicing resistance training, especially through modulation of nitric oxide signaling. Objectives: The aim of this study was therefore to investigate selected 'NO-boosting' supplements in a real-life setting i) to generate novel hypotheses and perfusion estimates for power calculation in view of a definitive trial and ii) to assess the feasibility of the study design with particular focus on the use of contrast-enhanced ultrasound (CEUS) for perfusion quantification. Methods: Thirty young male athletes (24 ± 4 years) regularly practicing resistance training were enrolled in this three-arm, placebo(PL)-controlled crossover trial with ingestion of two commercially available supplements: an amino acid combination (AA) (containing 3 g of L-arginine-hydrochloride and 8 g of L-citrulline-malate) and 300 mg of a specific green tea extract (GTE). After intake, CEUS examinations of the dominant biceps brachii muscle were performed under resting conditions and following standardized resistance exercising. Quantitative parameters of biceps perfusion (peak enhancement, PE; wash-in perfusion index, WiPI) and caliber were derived from corresponding CEUS video files. Additionally, subjective muscle pump was determined after exercise. Results: For PE, WiPI, and biceps caliber, the standard deviation (SD) of the within-subject differences between PL, AA, and GTE was determined, thereby allowing future sample size calculations. No significant differences between PL, AA, and GTE were observed for biceps perfusion, caliber, or muscle pump. When comparing resting with post-exercise measurements, the increase in biceps perfusion significantly correlated with the caliber increase (PE: r = 0.266, p = 0.0113; WiPI: r = 0.269, p = 0.0105). Similarly, the biceps perfusion correlated with muscle pump in the post-exercise conditions (PE: r = 0.354, p = 0.0006; WiPI: r = 0.350, p = 0.0007). A high participant adherence was achieved, and the acquisition of good quality CEUS video files was feasible. No adverse events occurred. Conclusion: Based on our novel examination protocol, CEUS seems to be feasible following higher-load resistance exercising and may be used as a new method for high-resolution perfusion quantification to investigate the effects of pre-exercise dietary supplementation on muscle perfusion and related muscle size dynamics.

Short-term results of gait analysis with the Heidelberg foot measurement method and functional outcome after operative treatment of ankle fractures.

BACKGROUND: Ankle fractures are common fractures in trauma surgery. Several studies have compared gait patterns between affected patients and control groups. However, no one used the Heidelberg Foot Measurement Method in combination with statistical parametric mapping of the entire gait cycle in this patient cohort. We sought to identify possible mobility deficits in the tibio-talar joint and medial arch in patients after ankle fractures as a sign of stiffness and pain that could result in a pathological gait pattern. We focused on the tibio-talar flexion as it is the main movement in the tibio-talar joint. Moreover, we examined the healing progress over time. METHODS: Fourteen patients with isolated ankle fractures were included prospectively. A gait analysis using the Heidelberg Foot Measurement Method was performed 9 and 26 weeks after surgery to analyse the tibio-talar dorsal flexion, the foot tibia dorsal flexion, the subtalar inversion and the medial arch as well as the cadence, the walking speed and the ground reaction force. The American Orthopedic Foot & Ankle Society ankle hindfoot score was used to obtain clinical data. Results were compared to those from 20 healthy participants. Furthermore, correlations between the American Orthopedic Foot & Ankle Society hindfoot score and the results of the gait analysis were evaluated. RESULTS: Statistical parametric mapping showed significant differences for the Foot Tibia Dorsal Flexion for patients after 9 weeks (53-75%: p = 0.001) and patients after 26 weeks (58-70%: p = 0.011) compared to healthy participants, respectively. Furthermore, significant differences regarding the tibio-talar dorsal flexion for patients 9 weeks after surgery (15-40%: p < 0.001; 56,5-70%: p = 0.007; 82-88%: p = 0.033; 97-98,5%: p = 0.048) as well as patients after 26 weeks (62,5-65%: p = 0.049) compared to healthy participants, respectively. There were no significant differences looking at the medial arch and the subtalar inversion. Moreover, significant differences regarding the ground reaction force were found for patients after 9 weeks (0-17%: p < 0.001; 21-37%: p < 0.001; 41-54%: p < 0.001; 60-64%: p = 0.013) as well as patients after 26 weeks (0-1,5%: p = 0.046; 5-15%: p < 0.001; 27-33%: p = 0.001; 45-49%: p = 0.005; 57-59%: p = 0.049) compared to healthy participants, respectively. In total, the range of motion in the tibio-talar joint and the medial arch was reduced in affected patients compared to healthy participants. Patients showed significant increase of the range of motion between 9 and 26 weeks. CONCLUSIONS: This study shows, that patients affected by ankle fractures show limited mobility in the tibio-talar joint and the medial arch when compared to healthy participants. Even though the limitation of motion remains at least over a period of 26 weeks, a significant increase can be recognized over time. Furthermore, if we look at the absolute values, the patients' values tend to get closer to those of the control group. TRIAL REGISTRATION: This study is registered at the German Clinical Trials Register ( DRKS00023379 ).

[Contrast-enhanced ultrasound in the diagnostics of non-unions]. / Kontrastmittelverstärkter Ultraschall in der Diagnostik von Pseudarthrosen.

Non-union represents a severe complication and a major socioeconomic challenge in orthopedics and trauma surgery. Timely and reliable diagnostics are obligatory to be able to carry out the treatment of non-unions in a patient-specific and efficient manner. Contrast-enhanced ultrasound (CEUS) is an important interface between clinical signs, imaging investigations and the results of the paraclinical diagnostics, e.g. C­reactive protein (CRP) and leukocyte count. It can display the microperfusion inside the non-union gap in real time and provide valuable information for exclusion of an infection or on the healing progress after revision surgery. An establishment of this diagnostic modality in routine orthopedic trauma surgery contributes to optimization of the treatment of non-unions.

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.

Promising results after hemi-shoulder arthroplasty using pyrolytic carbon heads in young and middle-aged patients.

INTRODUCTION: The objective of this prospective cohort study was the assessment of short-term outcome results of shoulder hemiarthroplasty (HA) using pyrolytic carbon (PC) heads. PC has been introduced as a new material to avoid surgical revision due to glenoid erosion after HA. Glenoid erosion due to the use of metallic heads is known to reduce durability. HYPOTHESIS: HA using PC heads shows comparable or better radiographic and clinical outcome compared to the conventional HA using metallic heads in the short-term. PATIENTS AND METHODS: This study was conducted as a single center prospective cohort follow-up study including a total number of 16 consecutive HA with PC heads. Inclusion criteria were indication for HA, an intact rotator cuff, no proximal humeral fractures in patient's history and age>18years. Mean age at the time of arthroplasty was 52.8±10.8years. The mean follow-up was 24.3±8.1months. Baseline and follow-up Numeric Rating Scale (NRS), Constant Scores (CS), Range of Motion (ROM) and radiographs were assessed. RESULTS: At a mean follow-up of 24.3months the mean CS (p<0.001), mean NRS (p<0.001) and mean ROM (p<0.05) improved statistically significant. Subgroup analysis revealed no differences between subgroups (sex, age, diagnosis, and handedness). Survival rate was high (94.1%). One periprosthetic fracture occurred as the only complication during follow-up. Radiographs showed glenoid erosion in one case and subacromial space reduction in two cases. DISCUSSION: PC heads in HA show satisfying short-term results at a mean follow-up of two years, which are comparable to those of conventional HA. The clinical improvements were highly significant with good implant survival. However, long-term follow-up results are necessary, especially compared to conventional HA. LEVEL OF EVIDENCE: IV; observational therapeutic cohort study.

The AMANDUS Project PART II-Advanced Microperfusion Assessed Non-Union Diagnostics with Contrast-Enhanced Ultrasound (CEUS): A Reliable Diagnostic Tool for the Management and Pre-operative Detection of Infected Upper-Limb Non-unions.

The management of upper-limb non-unions can be challenging, especially when infection is existent. Thus, pre-operative detection of infection plays a relevant role in non-union treatment. This study investigated in a large cohort the diagnostic potential of contrast-enhanced ultrasound (CEUS) as stand-alone method for differentiating between aseptic and infected upper-limb non-unions. Osseous perfusion of 50 upper-extremity non-unions (radius/ulna, n = 20; humerus, n = 22; clavicle, n = 8) was prospectively assessed with CEUS before revision surgery. The perfusion was quantified via time-intensity curves and peak enhancement (in arbitrary units). Significant perfusion differences between aseptic and infected non-unions could be detected (peak enhancement, p < 0.001). The sensitivity and specificity for the detection of infected upper-limb non-unions were 80% and 94.3% (cutoff peak enhancement: 130.8 arbitrary units). CEUS reliably differentiates between aseptic and infected upper-limb non-unions. Consequently, CEUS should be integrated into the daily diagnostic routine algorithm to plan non-union revision surgery more precisely as a single- or multi-step procedure.

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.

Contrast-enhanced ultrasound for determining muscular perfusion after oral intake of L-citrulline, L-arginine, and galloylated epicatechines: A study protocol.

INTRODUCTION: The market for dietary supplements in the sports sector has been growing rapidly for several years, though there is still lacking evidence regarding their claimed benefits. One group is that of nitric oxide increasing supplements, so-called "NO-boosters," which are claimed to improve the supply of oxygen and nutrients to the muscle by enhancing vasodilation.The aim of this study was to investigate 3 of these supplements in healthy male athletes for their muscle perfusion-enhancing potential using contrast-enhanced ultrasound (CEUS). METHODS: This placebo-controlled, double-blind, randomized cross-over trial will be carried out at the Center for Orthopedics, Trauma Surgery and Spinal Cord Injury of the University Hospital Heidelberg. Three commercial NO enhancing products including 300 mg of the specific green tea extract VASO6 and a combination of 8 g L-citrulline malate and 3 g L-arginine hydrochloride will be examined for their potential to increase muscular perfusion in 30-male athletes between 18 and 40 years and will be compared with a placebo. On each of the 3 appointments CEUS of the dominant biceps muscle will be performed at rest and after a standardized resistance training. Every athlete receives each of the 3 supplements once after a wash-out period of at least 1 week. Perfusion will be quantified via VueBox quantification software. The results of CEUS perfusion measurements will be compared intra- and interindividually and correlated with clinical parameters. DISCUSSION: The results of this study may help to establish CEUS as a suitable imaging modality for the evaluation of potentially vasodilatory drugs in the field of sports. Other supplements could also be evaluated in this way to verify the content of their advertising claims. TRIAL REGISTRATION: German Clinical Trials Register (DRKS), ID: DRKS00016972, registered on 25.03.2019.

Differences in gait analysis and clinical outcome after TightRope® or screw fixation in acute syndesmosis rupture: study protocol for a prospective randomized pilot study.

BACKGROUND: Ankle sprains and fractures are most common injuries in orthopedic and trauma surgery. The concurrent occurrence of syndesmosis ruptures in these injuries represents a more complex problem, as they often remain undetected. A proper and accurate treatment of injuries of the syndesmosis, both isolated and combined with fractures, is necessary to avoid long-term consequences (chronic instability, cartilage damage, and post-traumatic osteoarthritis). The most popular treatment option is a static screw fixation and the newly developed dynamic TightRope® (Arthrex, Naples, FL, USA). The aim of this pilot study is to compare monitor ankle range of motion and maximum ankle power in gait as functional outcome parameters of instrumented gait analysis, as well as clinical and radiographic outcome for assessing the stabilization of acute syndesmosis rupture with either a static implant (a 3.5 mm metallic screw) or a dynamic device (TightRope®). METHODS: This prospective, randomized, controlled, clinical trial will be carried out at the Center for Orthopedics, Trauma Surgery and Spinal Cord Injury of the University Hospital Heidelberg. Adult patients, who suffer from an acute syndesmosis rupture, both isolated and in combination with fractures of the lateral malleolus (Weber C and Maisonneuve fractures) and who are undergoing surgery at our trauma center will be included in our study. The patients will be randomized to the different treatment options (screw fixation or "TightRope®"). Subsequent to the surgical treatment, all patients will receive the same standardized follow-up procedures including a gait analysis and MRI of the ankle at 6 months follow-up. The primary endpoint of the study is the successful healing of the syndesmosis and biomechanical investigation with gait analysis. DISCUSSION: The results of the gait analysis from the current study will help to impartially and reliably evaluate the clinical and biomechanical outcome of both treatment options of acute syndesmosis ruptures. We hypothesize that the dynamic fixation provides an equivalent or better biomechanical, clinical, and radiographic outcome in comparison to the screw fixation. TRIAL REGISTRATION: German Clinical Trials Register (DRKS) DRKS00013562 . Registered on July, 12, 2017.

Safety Profile of Musculoskeletal Contrast-Enhanced Ultrasound with Sulfur Hexafluoride Contrast Agent.

PURPOSE: Muscle, bone and tendon regeneration depend on the microperfusion of the corresponding tissue which can be quantified with contrast-enhanced ultrasound (CEUS) using sulfur hexafluoride contrast agent (SonoVue®). This study investigated the incidence of adverse events (AEs) in musculoskeletal patients and gives an overview of musculoskeletal CEUS applications. PATIENTS AND METHODS: Based on 13 studies in a standardized monocentric setting, a total of 2268 CEUS examinations in 764 patients were performed and AEs due to the administration of sulfur hexafluoride contrast agent were classified as either mild, moderate or severe. RESULTS: No fatal events occurred. AEs were reported in three cases, of which only one was classified as severe and two as mild. The total rate of all AEs was 0.13% and 0.04% for severe AEs. CONCLUSION: The present analysis confirms the safety of musculoskeletal CEUS using sulfur hexafluoride contrast agent with a lower rate of AEs than that reported for other contrast agents even in elderly patients with concomitant diseases.

The AMANDUS Project-Advanced Microperfusion Assessed Non-Union Diagnostics With Contrast-Enhanced Ultrasound (CEUS) for the Detection of Infected Lower Extremity Non-Unions.

The pre-operative determination of infection plays a decisive role in non-union treatment. This study investigated in a large cohort the diagnostic potential of contrast-enhanced ultrasound (CEUS) as stand-alone method for the differentiation between aseptic and infected non-unions. Of 109 patients with lower extremity non-unions (tibia n = 78, femur n = 31) osseous perfusion with CEUS was prospectively assessed before revision surgery. The perfusion was quantified via time-intensity curves and peak enhancement (PE) (arbitrary unit [au]). Significant perfusion differences between aseptic and infected non-unions were evident (PE, p < 0.001). The sensitivity and specificity for the detection of infected tibial and femoral non-unions could be determined with 85.1% and 88.7% (cutoff PE: 81.2 au). CEUS illustrates tibial and femoral non-union perfusion in real time and discriminates reliably between aseptic and infected non-unions. Consequently, when CEUS is integrated into the diagnostic routine algorithm, non-union revision surgery can be planned more accurately as a single or multistep procedure.

Contrast-Enhanced Ultrasound Quantifies the Perfusion Within Tibial Non-Unions and Predicts the Outcome of Revision Surgery.

Vascularity is one of the factors determining successful bone regeneration. This prospective study focused on quantifying the microperfusion of tibial non-unions with contrast-enhanced ultrasound (CEUS) 12 wk after revision surgery and comparing it with the osseous consolidation at a maximum of 24 mo assessed with standard radiography and computed tomography. Of 36 patients with tibial non-unions, 28 (77.8%) manifested consolidation, and 8 patients required further revision surgery. CEUS revealed significantly higher perfusion in consolidated versus persistent non-unions for all quantification parameters (e.g., wash-in perfusion index p = 0.036). Receiver operating characteristic analysis revealed a sensitivity of 82.1% and specificity of 75.0% with a wash-in perfusion index cutoff at 19.9 a.u. for diagnosing persisting non-unions. More than 1 y ahead of the final radiologic diagnostic examination, CEUS could predict eventual consolidation based on the osseous perfusion as soon as 12 wk postoperatively. This information can be crucial for the decision-making process for re-revision at an early stage.

Safety study: is there a pathologic IGF-1, PDGF and TGF-ß cytokine expression caused by adjunct BMP-7 in tibial and femoral non-union therapy?

BACKGROUND: In this prospective safety study, we investigated if the characteristic cytokine expression during bone regeneration is manipulated by the local application of bone morphogenetic protein-7 (BMP-7) in non-union surgery. Therefore, the levels of insulin like growth factor 1 (IGF-1), platelet-derived growth factor AB (PDGF-AB) and transforming growth factor beta (TGF-ß) were compared between patients with the gold standard use of autologous bone graft (ABG) and those with additional application of BMP-7 as part of the diamond concept. PATIENTS AND METHODS: Between 2009 and 2014, of the 153 patients with tibial and femoral non-unions, a matched pair analysis was performed to compare the serological cytokine expressions. Blood samples were collected preoperatively, 1, 2 and 6 weeks as well as 3 and 6 months after non-union surgery. Matching criteria were smoking status, fracture location, gender, age and body mass index (BMI). Patients in G1 (n=10) were treated with ABG and local BMP-7 while their matching partners in G2 (n=10) received ABG only. The routine clinical and radiologic follow-up was 1 year. RESULTS: Although the IGF-1 quantification in G2 showed higher pre- and postoperative values compared to G1 (p<0.05), the courses of both groups were similar. Likewise, PDGF-AB and TGF-ß expressions appeared similar in G1 and G2 with peaks in both groups at 2 weeks follow-up. Osseous consolidation was assessed in all operated non-unions. The adjunct application of BMP-7 did not cause any pathologic cytokine expression. CONCLUSION: Similar expressions of the serum cytokines IGF-1, PDGF-AB and TGF-ß were demonstrated in non-union patients treated with ABG and additional application of BMP-7 according to the diamond concept. Our findings indicate that the local application of BMP-7, which imitates the physiologic secretion of growth factors during bone regeneration, is safe and without the risk of abnormal systemic cytokine expression. Studies with higher patient numbers will have to validate these assumptions.