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.

Reduced Sodium Portions Favor Osteogenic Properties and Cytocompatibility of 45S5-Based Bioactive Glass Particles.

Besides its favorable biological properties, the release of sodium (Na) from the well-known 45S5-bioactive glass (BG) composition (in mol%: 46.1, SiO2, 24.5 CaO, 24.5 Na2O, 6.0 P2O5) can hamper its cytocompatibility. In this study, particles of Na-reduced variants of 45S5-BG were produced in exchange for CaO and P2O5 via the sol-gel-route resulting in Na contents of 75%, 50%, 25% or 0% of the original composition. The release of ions from the BGs as well as their impact on the cell environment (pH values), viability and osteogenic differentiation (activity of alkaline phosphatase (ALP)), the expression of osteopontin and osteocalcin in human bone-marrow-derived mesenchymal stromal cells in correlation to the Na-content and ion release of the BGs was assessed. The release of Na-ions increased with increasing Na-content in the BGs. With decreasing Na content, the viability of cells incubated with the BGs increased. The Na-reduced BGs showed elevated ALP activity and a pro-osteogenic stimulation with accelerated osteopontin induction and a pronounced upregulation of osteocalcin. In conclusion, the reduction in Na-content enhances the cytocompatibility and improves the osteogenic properties of 45S5-BG, making the Na-reduced variants of 45S5-BG promising candidates for further experimental consideration.

Quantifying the effects of achilles tendon lengthening surgery: An intraoperative approach.

Achilles tendon lengthening (ATL) is frequently used in the treatment of foot deformities. However, there is currently no objective method to determine the optimal muscle length during surgery. We developed an intraoperative approach to evaluate the passive and active forces of the triceps surae muscle group before and after ATL and aimed to test the following hypotheses: 1) the ankle passive range of motion (ROM) increases, 2) passive muscle forces decrease post-ATL, and 3) forces measured from patients with non-neurological and neurological conditions demonstrate different characteristics. Passive forces at various ankle joint positions were measured in ten patients (11.3 ± 3.0 years old) pre- and post-ATL using a force transducer attached to the Achilles tendon. In six patients, active isometric forces were measured by stimulating the triceps surae supramaximally. Passive forces decreased by 94.3% (p < 0.0001), and ROM increased by 89.4% (p < 0.0001) post-ATL. The pre-ATL passive forces were 70.8% ± 15.1% lower in patients with idiopathic foot deformities than in patients with neurological conditions (p < 0.001). The peak active force of 209.8 ± 114.3 N was achieved at an ankle angle of 38.3° ± 16.0°, where the passive force was 6.3 ± 6.7 N. The inter-individual variability was substantial in both groups. In conclusion, the hypotheses posed were supported. The present findings suggest that muscle passive and active force production as well as the inter-individual variability should be considered when planning further treatment.

Transversal Malalignment and Proximal Involvement Play a Relevant Role in Unilateral Cerebral Palsy Regardless the Subtype.

Classification of gait disorders in cerebral palsy (CP) remains challenging. The Winters, Gage, and Hicks (WGH) is a commonly used classification system for unilateral CP regarding the gait patterns (lower limb kinematics) solely in the sagittal plane. Due to the high number of unclassified patients, this classification system might fail to depict all gait disorders accurately. As the information on trunk/pelvic movements, frontal and transverse planes, and kinetics are disregarded in WGH, 3D instrumented gait analysis (IGA) for further characterization is necessary. The objective of this study was a detailed analysis of patients with unilateral CP using IGA taking all planes/degrees of freedom into account including pelvic and trunk movements. A total of 89 individuals with unilateral CP matched the inclusion criteria and were classified by WGH. Subtype-specific differences were analyzed. The most remarkable findings, in addition to the established WGH subtype-specific deviations, were pelvic obliquity and pelvic retraction in all WGH types. Furthermore, the unclassified individuals showed altered hip rotation moments and pelvic retraction almost throughout the whole gait cycle. Transversal malalignment and proximal involvement are relevant in all individuals with unilateral CP. Further studies should focus on WGH type-specific rotational malalignment assessment (static vs. dynamic, femoral vs. tibial) including therapeutic effects and potential subtype-specific compensation mechanisms and/or tertiary deviations of the sound limb.

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.

GMFCS Level-Specific Differences in Kinematics and Joint Moments of the Involved Side in Unilateral Cerebral Palsy.

A variety of gait pathologies is seen in cerebral palsy. Movement patterns between different levels of functional impairment may differ. The objective of this work was the evaluation of Gross Motor Function Classification System (GMFCS) level-specific movement disorders. A total of 89 individuals with unilateral cerebral palsy and no history of prior treatment were included and classified according to their functional impairment. GMFCS level-specific differences, kinematics and joint moments, exclusively of the involved side, were analyzed for all planes for all lower limb joints, including pelvic and trunk movements. GMFCS level I and level II individuals most relevantly showed equinus/reduced dorsiflexion moments, knee flexion/reduced knee extension moments, reduced hip extension moments with pronounced flexion, internal hip rotation and reduced hip abduction. Anterior pelvic tilt, obliquity and retraction were found. Individuals with GMFCS level II were characterized by an additional pronounced reduction in all extensor moments, pronounced rotational malalignment and reduced hip abduction. The most striking characteristics of GMFCS level II were excessive anterior pelvic/trunk tilt and excessive trunk obliquity. Pronounced reduction in extensor moments and excessive trunk lean are distinguishing features of GMFCS level II. These patients would benefit particularly from surgical treatment restoring pelvic symmetry and improving hip abductor leverage. Future studies exploring GMFCS level-specific compensation of the sound limb and GMFCS level-specific malalignment are of interest.

Validation of a new Equinometer device for measuring ankle range of motion in patients with cerebral palsy: An observational study.

ABSTRACT: The goniometer is the gold-standard measurement tool of ankle range of motion (ROM). However, several studies have questioned its inter- and intra-rater reliability. Therefore, we conducted this validation study to assess the reliability of a different tool, named Equinometer, as a measurement device of ankle ROM in addition to comparing the reproducibility of their results.Sixteen healthy individuals were included. They underwent both goniometer and Equinometer measurements in knee extension and 90° knee flexion (Silfverskjöld Test). Three raters reported the values of dorsiflexion (DF) and plantarflexion (PF) in each session using both measurement tools. Intra-rater reliability was assessed between 2 raters on another study group of 24 participants. Intraclass correlation coefficients were used to determine the reliability of the used device.The age of study subjects ranged from 22 to 85 years. Fifty percent were males, and the right ankle joint was the most examined side (68.75%). In terms of DF and PF during knee extension and flexion, our analysis revealed that the measurements recorded by the Equinometer were equivalent to the goniometer. Of note, the intra-rater reliability of the Equinometer was excellent for both DF and PF assessment during both knee flexion and extension (Intraclass correlation coefficient ranged from 0.90 to 0.98), with minimal mean differences from goniometer measurements. Subgroup analysis based on age did not reveal any significant differences (P > .05).Given the high intra-rater correlations of the Equinometer, we suggest that it is reliable and precise in recording ankle ROM in outpatient clinics, particularly to obtain reproductive, comparable and unbiased data from different observers.

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.

Gait Indices for Characterization of Patients with Unilateral Cerebral Palsy.

As cerebral palsy (CP) is a complex disorder, classification of gait pathologies is difficult. It is assumed that unclassified patients show less functional impairment and less gait deviation. The aim of this study was to assess the different subgroups and the unclassified patients with unilateral CP using different gait indices. The Gillette Gait Index (GGI), Gait Deviation Index (GDI), Gait Profile Score (GPS) and spatiotemporal parameters derived from instrumented 3D-Gait Analysis (IGA) were assessed. Subgroups were defined using morphological and functional classification systems. Regarding the different gait indices, a ranking of the different gait patterns is evident. Significant differences were found between GMFCS level I and II, Winters et al. (Winters, Gage, Hicks; WGH) type IV and type I and the WGH-unclassified. Concerning the spatiotemporal parameters significant differences were found between GMFCS level I and II concerning velocity. The unclassified patients showed mean values for the different gait indices that were comparable to those of established subgroups. Established gait patterns cause different degrees of gait deviation and functional impairment. The unclassified patients do not differ from established gait patterns but from the unimpaired gait. Further evaluation using 3D-IGA is necessary to identify the underlying gait pathologies of the unclassified patients.

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.

Gait Classification in Unilateral Cerebral Palsy.

As unilateral cerebral palsy represents a complex disorder, gait classification is difficult. Knowledge of the most frequent gait patterns and functional impairment is crucial for proper decision-making. This study analyzes the prevalence of gait patterns as well as the relation of different gait patterns and the Gross Motor Function Classification System (GMFCS). Eighty-nine patients were classified retrospectively using the GMFCS, the classification of Winters, Gage, and Hicks (WGH), and Sutherland et al. The distribution of GMFCS levels among the different gait patterns was analyzed using Chi-squared test. The most common subtypes were GMFCS level I, WGH type I, and recurvatum knee. Seventeen percent (WGH) and 59% (Sutherland) of the patients did not match any criteria. Applying both classifications complementarily reduced the number of unclassified patients significantly. There was no significant difference concerning the distribution of GMFCS levels or age among the different gait patterns. A combined use of various classification systems is beneficial for proper decision-making. Unclassified patients seem to be a heterogeneous subgroup concerning functional impairment. There is a need of further characterization of the unclassifiable gait patterns and the caused functional impairment. Instrumented gait analysis remains the gold standard and should be broadly used for future studies and in clinical practice.

Femoral neck prostheses: A systematic analysis of the literature.

Primary total hip arthroplasty (THA) is one of the most successful surgical procedures. Considering the demographic change the use of new ultra-short femoral implants has gained importance especially when treating young patients. Main features are bone conservation, metaphyseal anchoring and thus reducing stress shielding by proximal load transferring. The objective of this study is to give an overview over the subject of femoral neck prostheses. A systematic review was conducted. A total number of 27 publications were taken into this systematic review. Over all, just a few follow-up, biomechanical and radiostereometric studies have been conducted in the past. Still no long-term results (>10 years of follow-up) are available. The available mid-term results indicate unsatisfactory survival rates. Aseptic loosening was the most common reason for revision. Valgus angle and good bone mineral density were considered to be crucial for primary stability of femoral neck prostheses. Register data report a very low percentage of femoral neck prostheses in THA with even more diminishing implantation rates. To conclude, further studies are necessary in order to provide evidence-based recommendations. Currently, due to the inhomogeneous and poor data a reasonable and legitimate recommendation cannot be given.

Periprosthetic fracture morphology of a femoral neck prosthesis: An in vitro study.

Femoral neck prostheses have been developed for the treatment of osteoarthritis in young and active patients. The concept combines a bone-conserving and minimal invasive technique with proximal load transferring by metaphyseal anchoring, which results in a more physiological loading pattern. However, little is known about the morphology of periprosthetic fractures. Thus, the aim of this study was to describe fracture patterns and to determine patient-specific factors favoring periprosthetic fracture. This study was performed as a biomechanical experimental study using 10 fresh frozen femora and 10 Silent-Hip femoral neck implants (DePuy International Ltd., Leeds, UK). In order to simulate physiological loading, a static muscle reconstruction (abductor muscles and iliotibial band) and a dynamic simulation of the gait cycle were applied. During biomechanical testing (50% and 100% of normal weight-bearing), three periprosthetic fractures with two different morphologies occurred. The first pattern corresponds to an abrupt breakaway. The second type was of spiral configuration extending to the diaphyseal region and emerging from an initial fissure. Specimen-specific factors favoring periprosthetic fracture were body mass index and varus angle of the implant. Periprosthetic fractures may extend to the subtrochanteric/diaphyseal region and may be of spiral configuration. According to the finding of this study, body mass index and varus/valgus position of the implant are important factors influencing the risk of periprosthetic fractures. Furthermore, partial weight-bearing as part of the postoperative regimen may be favorable.

Pooling of Patient-Derived Mesenchymal Stromal Cells Reduces Inter-Individual Confounder-Associated Variation without Negative Impact on Cell Viability, Proliferation and Osteogenic Differentiation.

Patient-derived mesenchymal stromal cells (MSCs) play a key role in bone tissue engineering. Various donor-specific factors were identified causing significant variability in the biological properties of MSCs impairing quality of data and inter-study comparability. These limitations might be overcome by pooling cells of different donors. However, the effects of pooling on osteogenic differentiation, proliferation and vitality remain unknown and have, therefore, been evaluated in this study. MSCs of 10 donors were cultivated and differentiated into osteogenic lineage individually and in a pooled setting, containing MSCs of each donor in equal parts. Proliferation was evaluated in expansion (assessment of generation time) and differentiation (quantification of dsDNA content) conditions. Vitality was visualized by a fluorescence-microscopy-based live/dead assay. Osteogenic differentiation was assessed by quantification of alkaline phosphatase (ALP) activity and extracellular calcium deposition. Compared to the individual setting, generation time of pooled MSCs was shorter and proliferation was increased during differentiation with significantly lower variances. Calcium deposition was comparable, while variances were significantly higher in the individual setting. ALP activity showed high variance in both groups, but increased comparably during the incubation period. In conclusion, MSC pooling helps to compensate donor-dependent variability and does not negatively influence MSC vitality, proliferation and osteogenic differentiation.

Prevalence and classification of equinus foot in bilateral spastic cerebral palsy.

BACKGROUND: Equinus is a common deformity in children with bilateral spastic cerebral palsy (BSCP). While dynamic equinus usually is treated by conservative therapy, fixed contractures need surgical correction. To choose the appropriate surgical method, it is important to discriminate between isolated gastrocnemius shortening and combined gastrosoleus complex contracture. METHODS: In a retrospective study 938 patients with BSCP were studied. Patients underwent gait analysis and clinical examination. 248 patients (496 limbs) met the inclusion criteria. Data from motion analysis and clinical examination were used to calculate the prevalence and to further classify fixed equinus foot. RESULTS: The prevalence of equinus was 83.3%. During clinical exam 246 (59.6%) limbs showed combined gastrosoleus complex contracture and 167 (40.4%) isolated gastrocnemius contracture. Max. DF at stance and mean DF at initial contact were significantly reduced in combined contracture, while max. ROM was increased (P < 0.05). CONCLUSIONS: Corroborating the results of previous studies, in this study there was a high prevalence of fixed equinus in patients with BSCP. The prevalence of equinus correlated with increasing age. As half of the patients with fixed equinus show a different involvement of gastrocnemius and soleus muscle, we recommend to apply Silfverskiöld's test to discriminate between those two types to choose the appropriate surgical therapy.

Biological Properties of Calcium Phosphate Bioactive Glass Composite Bone Substitutes: Current Experimental Evidence.

Standard treatment for bone defects is the biological reconstruction using autologous bone-a therapeutical approach that suffers from limitations such as the restricted amount of bone available for harvesting and the necessity for an additional intervention that is potentially followed by donor-site complications. Therefore, synthetic bone substitutes have been developed in order to reduce or even replace the usage of autologous bone as grafting material. This structured review focuses on the question whether calcium phosphates (CaPs) and bioactive glasses (BGs), both established bone substitute materials, show improved properties when combined in CaP/BG composites. It therefore summarizes the most recent experimental data in order to provide a better understanding of the biological properties in general and the osteogenic properties in particular of CaP/BG composite bone substitute materials. As a result, BGs seem to be beneficial for the osteogenic differentiation of precursor cell populations in-vitro when added to CaPs. Furthermore, the presence of BG supports integration of CaP/BG composites into bone in-vivo and enhances bone formation under certain circumstances.