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International journal of molecular sciences 23(13), 6920 (2022). doi:10.3390/ijms23136920 special issue: "Special Issue "Highlights in Pathophysiology of the Musculoskeletal System" / Special Issue Editors: Dr. Marta Anna Szychlinska, Guest Editor; Dr. Rosario Barone, Guest Editor", Published by Molecular Diversity Preservation International, Basel

Background and Objective Segmentation on carpus provides essential information for clinical applications including pathological evaluations, therapy planning, wrist biomechanical analysis, etc. Along with the acquisition procedure of magnetic resonance (MR) technique, poor quality of wrist images (e.g., occlusion, low signal-to-noise ratio, and contrast) often causes segmentation failure. Methods In this work, to address such problems, a shape prior enhanced level set model was proposed. By transferring a shape contour in Cartesian Coordinate System (COS) into a curve in Polar Coordinate System (POS), parameters describing conventional shape invariance, i.e., translations, rotation, and scale were simplified into a single parameter for phase shift, which strongly improved algorithm efficiency. Given a training set in COS, a confidence interval representing the corresponding curves in POS was utilized as the shape prior set term in the model. Integrated with an edge detector, a local intensity descriptor, and a regularization term, the proposed method further possessed abilities against noise, intensity inhomogeneity as well as re-initialization problem. Images from 15 in-vivo acquired MR-datasets of the human wrist were used for validation. The performance of the proposed method has been compared with three state-of-the-art methods. Results We reported a Dice Similarity Coefficient of 96.88±1.20%, a Relative Volume Difference of -1.53±3.01%, a Volume Overlap Error of 6.03±2.23%, a 95% Hausdorff Distance of 1.43±0.66 mm, an Average Symmetric Surface Distance of 0.50±0.17 mm, and a Root Mean Square Distance of 0.71±0.25 mm for the proposed method. The time consumption was 36.03±19.98 s. Conclusions Experimental results indicated that, compared with three other methods, the proposed method achieved significant improvement in terms of accuracy and efficiency.

Injury : international journal of the care of the injured 52(7), 1861-1867 (2021). doi:10.1016/j.injury.2021.04.058, Published by Elsevier Science, Amsterdam [u.a.]

Postgraduate medical education in trauma and orthopedic surgery residents largely relates to learning and teaching surgery. During this crucial stage of surgical development some of the didactic challenges are caused by heterogeneous and contradictory expectations of trainees and trainers alike. So how do residents prepare for emergency surgery? To date there is neither an expert consensus nor scientific investigations in the clinical context on this topic.Between February and April 2015 questionnaires were issued to all physicians active in the field of trauma and orthopedic surgery within the Trauma Network East Bavaria (27 clinics, 255 physicians). The participants were asked to rate the importance of certain elements functioning in the preparation of two emergency operations using a Likert scale. The intensity with which residents generally realize these elements of preparation was also documented. The aim was to objectify if and to what extent the presumed normal practices diverge from clinical reality.A total of 150 questionnaires were analyzed (return rate 59%). Discussion with the consultant (85.3%, n = 128), examination of the patient (80.0%, n = 120), surgical approach (76.0%, n = 114) and study of patient files (68.0%, n = 102) were considered to be the most important elements; however, many of the participants admitted that these elements of preparation are not sufficiently performed.The personal preparation of residents for an emergency operation should be classified as extremely important; however, the requirements and reality do not seem to hold true in the clinical environment. This seems to be most likely due to structural and organizational issues.HINTERGRUND: Die Weiterbildung im Fach Orthopädie/Unfallchirurgie ist wesentlich geprägt von „Operieren lehren und lernen“. In dieser elementaren Phase der chirurgischen Entwicklung dominieren aus didaktischer Sicht verschiedenste konträre Erwartungen und traditionelle Praktiken. Wie bereiten sich Weiterbildungsassistenten auf Notfalloperationen vor? Bis dato gibt es weder Expertenkonsens noch Untersuchungen im klinischen Kontext zu diesem Thema.Von Februar bis April 2015 wurden an alle klinisch tätigen Ärzte des Fachs Orthopädie/Unfallchirurgie im Traumanetzwerk Ostbayern (27 Kliniken, 255 Ärzte) anonymisierte Fragebögen ausgegeben. Jeder Teilnehmer konnte über Likert-Skalen die Wichtigkeit bestimmter Vorbereitungselemente für zwei Notfalloperationen bewerten sowie die Intensität, mit der Weiterbildungsassistenten generell diese Vorbereitungselemente realisieren. Die zentrale Fragestellung war, inwiefern Anspruch und Realität der Operationsvorbereitung voneinander abweichen.Der Rücklauf der Fragebögen lag bei 59 %, 150 Bögen wurden analysiert. Die höchste Priorität wurde den Vorbereitungselementen „Kommunikation mit dem 1. Assistenten“ (85,3 % [n = 128]), Patientenvisite (80,0 % [n = 120]), Zugangsweg (76,0 % [n = 114]) und Studium Patientenakte (68,0 % [n = 102]) zugesprochen. Ein großer Teil der Befragten räumte ein, dass diese Vorbereitungselemente nicht suffizient realisiert würden.Die persönliche Vorbereitung eines Weiterbildungsassistenten auf eine Notfalloperation ist als äußerst wichtig einzustufen. Anspruch und Realität zeigen im klinischen Setting jedoch eine relevante Asymmetrie. Ursächlich stehen hierbei am ehesten strukturelle und organisatorische Probleme im Vordergrund.

Summary Background Articular cartilage degeneration is the hallmark change of osteoarthritis, a severely disabling disease with high prevalence and considerable socioeconomic and individual burden. Early, potentially reversible cartilage degeneration is characterized by distinct changes in cartilage composition and ultrastructure, while the tissue’s morphology remains largely unaltered. Hence, early degenerative changes may not be diagnosed by clinical standard diagnostic tools. Methods Against this background, this study introduces a novel method to determine the tissue composition non-invasively. Our method involves quantitative MRI parameters (i.e., T1, T1ρ, T2 and T 2 ∗ maps), compositional reference measurements (i.e., microspectroscopically determined local proteoglycan [PG] and collagen [CO] contents) and machine learning techniques (i.e., artificial neural networks [ANNs] and multivariate linear models [MLMs]) on 17 histologically grossly intact human cartilage samples. Results Accuracy and precision were higher in ANN-based predictions than in MLM-based predictions and moderate-to-strong correlations were found between measured and predicted compositional parameters. Conclusion Once trained for the clinical setting, advanced machine learning techniques, in particular ANNs, may be used to non-invasively determine compositional features of cartilage based on quantitative MRI parameters with potential implications for the diagnosis of (early) degeneration and for the monitoring of therapeutic outcomes.

Cartilage functionality is determined by tissue structure and composition. If altered, cartilage is predisposed to premature degeneration. This pathomimetical study of early osteoarthritis evaluated the dose-dependant effects of collagenase-induced collagen disintegration and proteoglycan depletion on cartilage functionality as assessed by serial T1, T1ρ, T2, and T2* mapping under loading. 30 human femoral osteochondral samples underwent imaging on a clinical 3.0 T MRI scanner (Achieva, Philips) in the unloaded reference configuration (δ0) and under pressure-controlled quasi-static indentation loading to 15.1 N (δ1) and to 28.6 N (δ2). Imaging was performed before and after exposure to low (LC, 0.5 mg/mL; n = 10) or high concentration (HC, 1.5 mg/mL; n = 10) of collagenase. Untreated samples served as controls (n = 10). Loading responses were determined for the entire sample and the directly loaded (i.e. sub-pistonal) and bilaterally adjacent (i.e. peri‑pistonal) regions, referenced histologically, quantified as relative changes, and analysed using adequate parametric and non-parametric statistical tests. Dose-dependant surface disintegration and tissue loss were reflected by distinctly different pre- and post-exposure response-to-loading patterns. While T1 generally decreased with loading, regardless of collagenase exposure, T1ρ increased significantly after HC exposure (p = 0.008). Loading-induced decreases in T2 were significant after LC exposure (p = 0.006), while changes in T2* were ambiguous. In conclusion, aberrant loading-induced changes in T2 and T1ρ reflect moderate and severe matrix changes, respectively, and indicate the close interrelatedness of matrix changes and functionality in cartilage.

To measure sodium relaxation times and concentrations in human wrists on a clinical magnetic resonance imaging (MRI) scanner with a density-adapted radial sequence.Sodium MRI of human wrists was conducted on a 3T MR system using a dual-tunedNo differences for transversal of longitudinal relaxation times were found between RCJ and MCJ (TWe successfully determined sodium relaxation times and concentrations of the human wrist on a 3T MRI scanner.

Magnetic resonance imaging (MRI) under mechanical loading, commonly referred to as stress MRI, allows the evaluation of functional properties of intra- and periarticular tissues non-invasively beyond static assessment. Quantitative MRI can identify physiological and pathological responses to loading as indication of, potentially treatable, early degeneration and load transmission failure. Therefore, we have developed and validated an MRI-compatible pressure-controlled axial loading device to compress human knee specimens under variable loading intensity and axis deviation. Ten structurally intact human knee specimens (mean age 83.2 years) were studied on a 3.0T scanner (Achieva, Philips). Proton density-weighted fat-saturated turbo spin-echo and high-resolution 3D water selective 3D gradient-echo MRI scans were acquired sequentially at 10° joint flexion in seven configurations: unloaded and then at approximately half and full body weight loading in neutral, 10° varus and 10° valgus alignment, respectively. Following manual segmentation in both femorotibial compartments, cartilage thickness (ThC) was determined as well as meniscus extrusion (ExM). These measures were compared to computed tomography scans, histological grading (Mankin and Pauli scores), and biomechanical properties (Instantaneous Young's Modulus). Compartmental, regional and subregional changes in ThC and ExM were reflective of loading intensity and joint alignment, with the greatest changes observed in the medial compartment during varus and in the lateral compartment during valgus loading. These were not significantly associated with the histological tissue status or biomechanical properties. In conclusion, this study explores the physiological in-situ response of knee cartilage and meniscus, based on stress MRI, and as a function of loading intensity, joint alignment, histological tissue status, and biomechanical properties, as another step towards clinical implementation.

The aim of this study was to assess the impact of Peyton's 4-step approach on musculoskeletal ultrasound skills in a peer-teaching environment as compared to traditional "see one, do one" training and to evaluate students' acceptance of the training strategy.A total of 491 second year medical students (342 women, 149 men) completed a compulsory curricular course on musculoskeletal ultrasound. We randomly assigned students to receive traditional peer teaching or peer teaching using Peyton's four-step approach in small groups. All groups received theoretical and practical hands-on training of selected views of the knee and shoulder. We assessed differences in practical skills (objective structured practical examination, OSPE) and evaluation results with respect to teaching strategy.There were no relevant differences between the two teaching interventions regarding the OSPE results. Students scored significantly higher in the knee view (knee 6.5 ± 1.7 points, shoulder 6.0 ± 1.9 points; p 0.001), needed less time to display the required image (knee 36 ± 21 s, shoulder 43 ± 20 s; p 0.001) and more students obtained the cut-off mark of 60% to pass the exam (knee 73%, shoulder 61%; p 0.001). Acceptance of the peer-teaching concept was high, and the overall rating of the instructors was good. The majority of students enjoyed the course and rated it highly.Traditional teaching and Peyton's 4-step approach seem to be equally effective for teaching basic musculoskeletal ultrasound skills to undergraduate medical students. Qualitative analysis revealed high acceptance of both peer teaching strategies. Differences in course content complexity and degree of difficulty need to be addressed in future courses.Der Ultraschall der Bewegungsorgane findet breite Anwendung in der Diagnostik von Pathologien und in der Intervention. Die frühe Implementierung von Ultraschallkursen in das medizinische Curriculum könnte zu einer besseren medizinischen Versorgung führen. Die Sonografie wird häufig mit der „See one, do one“-Methode angeleitet, obgleich unklar bleibt, ob dies die beste Herangehensweise darstellt. Die vorliegende Arbeit untersucht, ob die 4-Schritt-Methode nach Peyton konventionellen Lehrstrategien in der Vermittlung des muskuloskelettalen Ultraschalls durch Peer-Dozierende überlegen ist und wie die Technik von den Studierenden beurteilt wird.Insgesamt absolvierten 491 Studierende (342 Frauen, 149 Männer) eine curriculare Lehrveranstaltung zum Thema Gelenksonografie. Ausgesuchte Schnitte an Knie und Schulter wurden randomisiert auf konventionelle Weise und nach der 4-Schritt-Methode nach Peyton von speziell geschulten Peer-Dozierenden unterrichtet. Die erlernten Fertigkeiten wurden in einer Objective structured practical Examination (OSPE) geprüft. Beurteilt wurde die benötigte Zeit zum Einstellen der Schnitte, die technische Durchführung und die Bildqualität. Die Studierenden wurden gebeten, den Kurs zu evaluieren.Bezüglich der praktischen Ausführung und der Qualität der Schnittbilder zeigten sich die beiden Lehrmethoden sowohl für die Schulter- als auch für die Kniegelenksonografie als ebenbürtig. Der Vergleich der Lehrinhalte (Knie vs. Schulter) hatte signifikante Differenzen bezüglich der Bildauswertung (Knie 6,5 ± 1,7 Punkte, Schulter 6,0 ± 1,9 Punkte; p 0,001), der benötigten Zeit (Knie 36 ± 21 s, Schulter 43 ± 20 s; p 0,001) und des Erreichens der Bestehensgrenze von 60% (Knie: 73% der Studierenden, Schulter: 61% der Studierenden; p 0,001) gezeigt. Unabhängig von der Lehrmethode bewerteten die Studierenden die Peer-Dozierenden als kompetent und befanden die Inhalte als adäquat für den Unterricht durch Gleichgestellte. Über 70% der Studierenden hatten Spaß an den Kursstunden. Sowohl der Knie- als auch der Schultergelenkkurs wurden im Mittel mit über 8 von 10 Punkten bewertet.Für die Vermittlung von Grundkenntnissen der Gelenksonografie sind die konventionelle Methode und die 4-Schritt-Methode nach Peyton ebenbürtig. Die Durchführung des Unterrichts durch Peer-Dozierende wird positiv bewertet und findet hohe Akzeptanz bei den Studierenden. Unterschieden im Schwierigkeitsgrad und der Komplexität der Lehrinhalte ist in künftigen Kursen Rechnung zu tragen.

Open reduction and internal fixation (ORIF) using an extended lateral approach combined with plate osteosynthesis represents the current gold standard in calcaneal fracture treatment, but it is associated with a wound complication rate of up to 30%. Literature suggests that micro-circulation is one of the key factors for sufficient wound healing. The aim of this study was to evaluate soft tissue micro-circulation of the hindfoot in healthy volunteers to determine influencing factors and to identify hypoxic or hypoperfused areas in non-trauma situations, with special attention to surgical approaches. Micro-circulation of the lateral hindfoot of 125 participants was non-invasively measured at 2 and 8 mm depths, utilizing a Micro-Lightguide O2C® spectrophotometer. Blood flow (BF [AU]) and oxygen saturation (SO2 [%]) of ten measurement points (MPs) were documented. Demographic factors (age, gender, body mass index [BMI], systolic/diastolic blood pressure, smoking, and pack-years) and regional differences with special regard to surgical approaches (extended lateral approach, Palmer approach, Ollier approach, and a self-modified extended lateral approach) were analyzed. The SO2 assessments at 2- and 8-mm depths revealed higher values in males (p = 0.043; p = 0.025). There was a correlation between higher age and lower 2 mm BF (p = 0.044). Smoking history and number of pack-years did not predict micro-circulation. BF at the 2 mm depth was highest in the regions of Palmer and Ollier approach (p

Summary Objective To define the physiological response to sequential loading and unloading in histologically intact human articular cartilage using serial T1ρ mapping, as T1ρ is considered to indicate the tissue's macromolecular content. Method 18 macroscopically intact cartilage-bone samples were obtained from the central lateral femoral condyles of 18 patients undergoing total knee replacement. Serial T1ρ mapping was performed on a clinical 3.0-T MRI system using a modified prostate coil. Spin-lock multiple gradient-echo sequences prior to, during and after standardized indentation loading (displacement controlled, strain 20%) were used to obtain seven serial T1ρ maps: unloaded (δ 0 ), quasi-statically loaded (indentation 1 –indentation 3 ) and under subsequent relaxation (relaxation 1 –relaxation 3 ). After manual segmentation, zonal and regional regions-of-interest were defined. ROI-specific relative changes were calculated and statistically assessed using paired t -tests. Histological (Mankin classification) and biomechanical (unconfined compression) evaluations served as references. Results All samples were histologically and biomechanically grossly intact (Mankin sum: 1.8 ± 1.2; Young's Modulus: 0.7 ± 0.4 MPa). Upon loading, T1ρ consistently increased throughout the entire sample thickness, primarily subpistonally (indentation 1 [M ± SD]: 9.5 ± 7.8% [sub-pistonal area, SPA] vs 4.2 ± 5.8% [peri-pistonal area, PPA]; P 3 : 14.1 ± 8.1 [SPA] vs 7.7 ± 5.9% [PPA]; P Conclusion Serial T1ρ-mapping reveals distinct and complex zonal and regional changes in articular cartilage as a function of loading and unloading. Thereby, longitudinal adaptive processes in hyaline cartilage become evident, which may be used for the tissue's non-invasive functional characterization by T1ρ.

Results suggest that focused, abbreviated biparametric prostate MR imaging is as useful to help detect clinically significant prostate cancer in men with elevated prostate-specific antigen as is regular, multiparametric prostate MR imaging.

The detection of early stages of cartilage degeneration remains diagnostically challenging. One promising non-invasive approach is to functionally assess the tissue response to loading by serial magnetic resonance (MR) imaging in terms of T2 mapping under simultaneous mechanical loading. As yet, however, it is not clear which cartilage component contributes to the tissue functionality as assessed by quantitative T2 mapping. To this end, quantitative T2 maps of histologically intact cartilage samples (n=8) were generated using a clinical 3.0-T MR imaging system. Using displacement-controlled quasi-static indentation loading, serial T2 mapping was performed at three defined strain levels and loading-induced relative changes were determined in distinct regions-of-interest. Samples underwent conventional biomechanical testing (by unconfined compression) as well as histological assessment (by Mankin scoring) for reference purposes. Moreover, an anisotropic hyperelastic constitutive model of cartilage was implemented into a finite element (FE) code for cross-referencing. In efforts to simulate the evolution of compositional and structural intra-tissue changes under quasi-static loading, the indentation-induced changes in quantitative T2 maps were referenced to underlying changes in cartilage composition and structure. These changes were parameterized as cartilage fluid, proteoglycan and collagen content as well as collagen orientation. On a pixel-wise basis, each individual component correlation with T2 relaxation times was determined by Spearman's ρs and significant correlations were found between T2 relaxation times and all four tissue parameters for all indentation strain levels. Thus, the biological changes in functional MR Imaging parameters such as T2 can further be characterized to strengthen the scientific basis of functional MRI techniques with regards to their perspective clinical applications.

Morphological imaging of cartilage at high resolution allows the differentiation of chondral and osteochondral lesions. Nowadays, magnetic resonance imaging is the principal diagnostic tool in the assessment of cartilage structure and composition. Conventional radiography, computed tomography, ultrasound or optical coherence tomography are adjunct diagnostic modalities in the assessment of cartilage pathologies. The present article discusses the up-to-date diagnostic practice of cartilage imaging in terms of its scientific basis and current clinical status, requirements, techniques and image interpretation. Innovations in the field such as functional MRI are discussed as well due to their mid- to long-term clinical perspective.

To reduce mechanical complications after osteosynthesis of femoral neck fractures, improved fixation techniques have been developed including blade or screw–anchor devices. This biomechanical study compares different fixation systems used for treatment of unstable femoral neck fractures with evaluation of failure mode, load to failure, stiffness, femoral head rotation, femoral neck shortening and femoral head migration. Standardized Pauwels type 3 fractures (AO/OTA 31-B2) with comminution were created in 18 biomechanical sawbones using a custom-made sawguide. Fractures were stabilized using either SHS-Screw, SHS-Blade or Rotationally Stable Screw-Anchor (RoSA). Femurs were positioned in 25 degrees adduction and ten degrees posterior flexion and were cyclically loaded with an axial sinusoidal loading pattern of 0.5 Hz, starting with 300 N, with an increase by 300 N every 2000 cycles until bone–implant failure occurred. Mean failure load for the Screw-Anchor fixation (RoSA) was 5100 N (IQR 750 N), 3900 N (IQR 75 N) for SHS-Blade and 3000 N (IQR 675 N; p = 0.002) for SHS-Screw. For SHS-Screw and SHS-Blade we observed fracture displacement with consecutive fracture collapse as the main reason for failure, whereas RoSA mainly showed a cut-out under high loadings. Mean stiffness at 1800 N was 826 (IQR 431) N/mm for SHS-Screw, 1328 (IQR 441) N/mm for SHS-Blade and 1953 (IQR 617) N/mm for RoSA (p = 0.003). With a load of 1800 N (SHS-Screw 12° vs. SHS-Blade 7° vs. RoSA 2°; p = 0.003) and with 2700 N (24° vs. 15° vs. 3°; p = 0.002) the RoSA implants demonstrated a higher rotational stability and had the lowest femoral neck shortening (p = 0.002), compared with the SHS groups. At the 2700 N load point, RoSA systems showed a lower axial (p = 0.019) and cranial (p = 0.031) femoral head migration compared to the SHS-Screw. In our study, the new Screw-Anchor fixation (RoSA) was superior to the comparable SHS implants regarding rotational stability and femoral neck shortening. Failure load, stiffness, femoral head migration, and resistance to fracture displacement were in RoSA implants higher than in SHS-Screws, but without significance in comparison to SHS-Blades.

Distributed adversarial networks can generate synthesized radiographs, yielding better classification while maintaining privacy., Computer vision (CV) has the potential to change medicine fundamentally. Expert knowledge provided by CV can enhance diagnosis. Unfortunately, existing algorithms often remain below expectations, as databases used for training are usually too small, incomplete, and heterogeneous in quality. Moreover, data protection is a serious obstacle to the exchange of data. To overcome this limitation, we propose to use generative models (GMs) to produce high-resolution synthetic radiographs that do not contain any personal identification information. Blinded analyses by CV and radiology experts confirmed the high similarity of synthesized and real radiographs. The combination of pooled GM improves the performance of CV algorithms trained on smaller datasets, and the integration of synthesized data into patient data repositories can compensate for underrepresented disease entities. By integrating federated learning strategies, even hospitals with few datasets can contribute to and benefit from GM training.

Background: To evaluate the value of 3 Tesla (T) magnetic resonance imaging (MRI) changes of flexor tendon pulleys for the differentiation of psoriatic (PsA) and rheumatoid arthritis (RA), using a novel 16-channel high resolution hand coil. Methods: Seventeen patients with active PsA, 20 patients with active RA and 16 healthy controls (HC) underwent high-resolution 3T MRI using the dedicated 16-channel hand coil. Images were analyzed by three independent readers for the degree of inflammatory changes, thickness of flexor tendon pulleys and comparison to the outcome measures for RA clinical trials (OMERACT) PsA MRI score (PsAMRIS) and to its sub-scores. For correlation analyses Spearman rho correlation was calculated. Results: Flexor tendon pulleys were thicker in PsA than in RA patients (mean difference 0.16 mm, p

Artificial intelligence (AI) has the potential to change medicine fundamentally. Here, expert knowledge provided by AI can enhance diagnosis by comprehensive and user independent integration of multiple image features. Unfortunately, existing algorithms often stay behind expectations, as databases used for training are usually too small, incomplete, and heterogeneous in quality. Additionally, data protection constitutes a serious obstacle to data sharing. We propose to use generative models (GM) to produce high-resolution artificial radiographs, which are free of personal identifying information. Blinded analyses by computer vision and radiology experts proved the high similarity of artificial and real radiographs. The combination of multiple GM improves the performance of computer vision algorithms and the integration of artificial data into patient data repositories can compensate for underrepresented disease entities. Furthermore, the low computational effort of our method complies with existing IT infrastructure in hospitals and thus facilitates its dissemination. We envision that our approach could lead to scalable databases of anonymous medical images enabling standardized radiomic analyses at multiple sites.

Purpose Wound healing complications are a major concern after open reduction and internal fixation (ORIF) in patients with calcaneal fractures. Microcirculation is known to play a key role in bone and soft tissue healing. The present study aimed to characterize and contrast the dynamics of changes in microcirculation comparing two different surgical procedures: A) ORIF and B) a minimally invasive approach (MIA). Methods Blood flow (BF[AU]), oxygen saturation (sO2[%]) and relative amount of haemoglobin (rHb[AU]) were measured at two depths (2mm and 8mm) non-invasively by spectrophotometry (Micro-Lightguide O2C®, LEA Medizintechnik, Giessen, Germany) before surgery and every 24h after surgery for a duration of six days. A linear mixed model (LMM) was used to analyse longitudinal data and repeated measurements. Results Nineteen patients (44 years, range 21.9–71.0 years) were enrolled in the study. Surgical treatment consisted of ORIF (n=15) and MIA (n=9). The postoperative BF and sO2 at the 2mm and 8mm depths were higher in the ORIF group (BF: p Conclusions The spectrophotometry results were in line with the generally accepted phases of soft tissue wound healing. Postsurgical changes in microcirculation are predominantly independent of surgical techniques and may be primarily determined by wound and fracture healing. Future studies should focus on the potential of spectrophotometry to monitor wound healing after surgery. Moreover, studies with longer observation periods are needed in order to examine the changes in microcirculation during all wound-healing phases.

To assess human articular cartilage tissue functionality by serial multiparametric quantitative MRI (qMRI) mapping as a function of histological degeneration. Forty-nine cartilage samples obtained during total knee replacement surgeries were placed in a standardized artificial knee joint within an MRI-compatible compressive loading device and imaged in situ and at three loading positions, i.e. unloaded, at 2.5 mm displacement (20% body weight [BW]) and at 5 mm displacement (110% BW). Using a clinical 3.0 T MRI system (Achieva, Philips), serial T1, T1ρ, T2 and T2* maps were generated for each sample and loading position. Histology (Mankin scoring) and biomechanics (Young’s modulus) served as references. Samples were dichotomized as intact (int, n = 27) or early degenerative (deg, n = 22) based on histology and analyzed using repeated-measures ANOVA and unpaired Student’s t-tests after log-transformation. For T1ρ, T2 and T2*, significant loading-induced differences were found in deg (in contrast to int) samples, while for T1 significant decreases in all zones were observed, irrespective of degeneration. In conclusion, cartilage functionality may be visualized using serial qMRI parameter mapping and the response-to-loading patterns are associated with histological degeneration. Hence, loading-induced changes in qMRI parameter maps provide promising surrogate parameters of tissue functionality and status in health and disease.

Culturing articular chondrocytes under physiological oxygen tension exerts positive effects on their extracellular matrix synthesis. The underlying molecular mechanisms which enhance the chondrocytic phenotype are, however, still insufficiently elucidated. The TGF-&beta, superfamily of growth factors, and the prototypic TGF-&beta, isoforms in particular, are crucial in maintaining matrix homeostasis of these cells. We employed a feedback-controlled table-top bioreactor to investigate the role of TGF-&beta, in microtissues of human chondrocytes over a wider range of physiological oxygen tensions (i.e., physoxia). We compared 1%, 2.5%, and 5% of partial oxygen pressure (pO2) to the &lsquo, normoxic&rsquo, 20%. We confirmed physoxic conditions through the induction of marker genes (PHD3, VEGF) and oxygen tension-dependent chondrocytic markers (SOX9, COL2A1). We identified 2.5% pO2 as an oxygen tension optimally improving chondrocytic marker expression (ACAN, COL2A1), while suppressing de-differentiation markers (COL1A1, COL3A1). Expression of TGF-&beta, isoform 2 (TGFB2) was, relatively, most responsive to 2.5% pO2, while all three isoforms were induced by physoxia. We found TGF-&beta, receptors ALK1 and ALK5 to be regulated by oxygen tension on the mRNA and protein level. In addition, expression of type III co-receptors betaglycan and endoglin appeared to be regulated by oxygen tension as well. R-Smad signaling confirmed that physoxia divergently regulated phosphorylation of Smad1/5/8 and Smad2/3. Pharmacological inhibition of canonical ALK5-mediated signaling abrogated physoxia-induced COL2A1 and PAI-1 expression. Physoxia altered expression of hypertrophy markers and that of matrix metalloproteases and their activity, as well as expression ratios of specific proteins (Sp)/Kr&uuml, ppel-like transcription factor family members SP1 and SP3, proving a molecular concept of ECM marker regulation. Keeping oxygen levels tightly balanced within a physiological range is important for optimal chondrocytic marker expression. Our study provides novel insights into transcriptional regulations in chondrocytes under physoxic in vitro conditions and may contribute to improving future cell-based articular cartilage repair strategies.

Biomechanical Magnetic Resonance Imaging (MRI) of articular cartilage, i.e. its imaging under loading, is a promising diagnostic tool to assess the tissue's functionality in health and disease. This study aimed to assess the response to static and dynamic loading of histologically intact cartilage samples by functional MRI and pressure-controlled in-situ loading. To this end, 47 cartilage samples were obtained from the medial femoral condyles of total knee arthroplasties (from 24 patients), prepared to standard thickness, and placed in a standard knee joint in a pressure-controlled whole knee-joint compressive loading device. Cartilage samples' responses to static (i.e. constant), dynamic (i.e. alternating), and no loading, i.e. free-swelling conditions, were assessed before (δ0), and after 30 min (δ1) and 60 min (δ2) of loading using serial T1ρ maps acquired on a 3.0T clinical MRI scanner (Achieva, Philips). Alongside texture features, relative changes in T1ρ (Δ1, Δ2) were determined for the upper and lower sample halves and the entire sample, analyzed using appropriate statistical tests, and referenced to histological (Mankin scoring) and biomechanical reference measures (tangent stiffness). Histological, biomechanical, and T1ρ sample characteristics at δ0 were relatively homogenous in all samples. In response to loading, relative increases in T1ρ were strong and significant after dynamic loading (Δ1 = 10.3 ± 17.0%, Δ2 = 21.6 ± 21.8%, p = 0.002), while relative increases in T1ρ after static loading and in controls were moderate and not significant. Generally, texture features did not demonstrate clear loading-related associations underlying the spatial relationships of T1ρ. When realizing the clinical translation, this in-situ study suggests that serial T1ρ mapping is best combined with dynamic loading to assess cartilage functionality in humans based on advanced MRI techniques.

Background:Even though cartilage loss is a known feature of psoriatic arthritis (PsA), little is known about its role in the pathogenesis of PsA. Using delayed gadolinium-enhanced magnetic resonance imaging of cartilage (dGEMRIC) as a non-invasive marker of the tissue’s proteoglycan content, such early (i.e. pre-morphological) changes have been associated with inflammation in rheumatoid arthritis (RA). Yet, this association has not been studied before in PsA.Objectives:Is the severity of local joint inflammation associated to local proteoglycan loss in PsA patients?Methods:Metacarpophalangeal (MCP), proximal interphalangeal (PIP), and distal interphalangeal (DIP) joints of 17 patients with active PsA were evaluated by high-resolution clinical standard morphological and dGEMRIC sequences using a 3T MRI scanner (Magnetom Skyra, Siemens) and a dedicated 16-channel hand coil. Images were analyzed by two independent raters for dGEMRIC indices, PsA MRI scores (PsAMRIS) and total cartilage thickness (TCT). Kendall-Tau correlation coefficients (τ) were calculated.Results:We found significant negative correlations between dGEMRIC indices and total PsAMRIS (τ = -0.5, p= 0.012), synovitis (τ = -0.56, p= 0.006), flexor tenosynovitis (τ = -0.4, p= 0.049), and periarticular inflammation (τ = -0.72, p< 0.001). Significant positive correlations were found between TCT and dGEMRIC indices in all joint levels (τ = 0.43, pConclusion:In PsA, proteoglycan loss as assessed by dGEMRIC is associated with periarticular inflammation, synovitis, and flexor tenosynovitis, but not with bone erosion or proliferation, thereby highlighting the need for effective anti-inflammatory treatment regimes. Beyond morphology, advanced MRI techniques may be used to assess cartilage composition in PsA and to identify early changes in cartilage as an imaging biomarker with potential application in detection and monitoring of PsA.Figure 1Right hand of a 26-year-old male with psoriatic arthritis Coronal STIR image (A) of digits 1-5, transversal fat-saturated (fs) T2-weighted image of digits 2-4 (B) and the corresponding transversal fs contrast-enhanced T1-weighted image (C) at the distal portion of the proximal phalanges. Horizontal white bar in (A) indicates level of transversal slices (B) & (C). Sagittal fs Proton Density-weighted image of the third digit (D). A: Increased signal at the collateral ligaments and synovitis of the proximal interphalangeal (PIP) joint of the third digit (white arrow). Periarticular inflammation around the PIP joint and the body of the proximal phalanx of the third digit (arrowhead). B & C: Extensive flexor tenosynovitis (asterix) and periarticular inflammation in the subcutaneous tissues (arrowhead) alongside thickened flexor tendon pulleys (arrow). D & E: Representative sagittal T1-weighted images of the MCP, PIP and DIP joint of the 3rd digit. Following iv contrast administration and appropriate delay of 40 min, A gives the morphological T1 map, while B gives the corresponding parameter map with dGEMRIC values [ms] overlaid. Note the significant decrease in dGEMRIC indices of the PIP joint as compared to the MCP joint.Disclosure of Interests:Philipp Sewerin Grant/research support from: AbbVie Deutschland GmbH & Co. KGBristol-Myers Squibb Celgene GmbHLilly Deutschland GmbHNovartis Pharma GmbH Pfizer Deutschland GmbHRheumazentrum Rhein-Ruhr, Consultant of: AMGEN GmbH AbbVie Deutschland GmbH & Co. KG Biogen GmbHBristol-Myers Squibb Celgene GmbH Chugai Pharma arketing Ltd. / Chugai Europe GmbHHexal Pharma Janssen-CilagGmbH Johnson & Johnson Deutschland GmbHLilly Deutschland GmbH / Lilly Europe / Lilly Global Novartis Pharma GmbH Pfizer Deutschland GmbH Roche Pharma Rheumazentrum Rhein-Ruhr Sanofi-Genzyme Deutschland GmbH Swedish Orphan Biovitrum GmbH UCB Pharma GmbH, Speakers bureau: AMGEN GmbH AbbVie Deutschland GmbH & Co. KG Biogen GmbHBristol-Myers Squibb Celgene GmbH Chugai Pharma arketing Ltd. / Chugai Europe GmbHHexal Pharma Janssen-CilagGmbH Johnson & Johnson Deutschland GmbHLilly Deutschland GmbH / Lilly Europe / Lilly Global Novartis Pharma GmbH Pfizer Deutschland GmbH Roche Pharma Rheumazentrum Rhein-Ruhr Sanofi-Genzyme Deutschland GmbH Swedish Orphan Biovitrum GmbH UCB Pharma GmbH, Daniel Abrar: None declared, Sven Nebelung: None declared, Miriam Frenken: None declared, Tim Ulrich: None declared, Karl Ludger Radke: None declared, Gerald Antoch: None declared, Stefan Vordenbäumen: None declared, Ralph Brinks: None declared, Matthias Schneider Grant/research support from: GSK, UCB, Abbvie, Consultant of: Abbvie, Alexion, Astra Zeneca, BMS, Boehringer Ingelheim, Gilead, Lilly, Sanofi, UCB, Speakers bureau: Abbvie, Astra Zeneca, BMS, Chugai, GSK, Lilly, Pfizer, Sanofi, Benedikt Ostendorf: None declared, Christoph Schleich: None declared

Background:In OA, there is a close association of meniscus and cartilage pathologies. Meniscus degeneration and lesioning are critical risk factors for development of early OA. Hence, thisex-vivostudy assessed the responses to standardized loading of human meniscus samples as a function of degeneration and based on changes in their T1, T2 and T1ρ maps (as surrogate parameters of the tissue’s functionality).Objectives:Can meniscus functionality be visualized by serial quantitative MRI mapping technics?Methods:During total knee replacements, 45 meniscus samples of variable degeneration were harvested from the center of the lateral meniscus body (Fig. 1a1-a3). After preparation to standard, samples were subject to force-controlled loading using an MRI-compatible lever device that created compressive loading by torque ((Fig. 1a4-a5). For each sample and loading position, MRI measurements (as detailed below) were performed in the unloaded (δ0) and loaded configurations, i.e. loaded to 2 bar (δ1, 37.1 N compressive force, 0.67 Nm torque) and to 4 bar (δ2, 69.1 N, 1.24 Nm). Throughout all loading positions, morphological and quantitative imaging was performed using Proton Density-weighted and T1, T1ρ, and T2 mapping sequences (3.0 T, Achieva, Philips) based on standard turbospin-echo, inversion-recovery, spin-lock multi-gradient-echo, and multi-spin-echo sequences. For reference purposes, histological (i.e. Pauli classification) and biomechanical measures (i.e. Elastic Modulus) were obtained for each sample. Based on Pauli sum scores, samples were trichotomized as grossly intact, (n=14), mildly degenerated (n=16), and moderate-to-severely degenerated (n=15).Figure 1.Preparation of meniscus samples and details of the MRI-compatible loading device. The lateral meniscus (a1) was cut to standard size by use of a dedicated cutting block (a2) to eventually obtain lateral meniscus samples (from the body region) of standard dimensions (a3). These samples were then placed in a dedicated MRI-compatible loading device for pressure-controlled, quasi-static and torque-induced loading under simultaneous MR imaging (a4). Two parallel support beams allowed standardized positioning in the MRI scanner‘s bore (a5).Results:Morphologically, loading induced deformation and flattening in all samples (Fig. 2a). For T1, homogeneous loading-induced decreases in all samples were found, irrespective of degeneration (Fig. 2b). For T1ρ, increases in the apical zones of intact samples were observed, and decreases in degenerated samples (Fig. 2c). For T2, changes were ambiguous and incoherent (Fig. 2d).Figure 2.Serial morphological images and functional maps of histologically moderately degenerative human meniscus as a function of force-controlled loading. Serial PDw (a), T1 (b), T1ρ (c), and T2 maps (d) are displayed at increasing loading intensity (δ0: unloaded [a1-d1]; δ1: loaded to 2 bar [a2-d2]; δ2: loaded to 4 bar [a3-d3]). Histologically, this sample demonstrated signs of severe surface desintegration and disruption. Pauli sum score 12, i.e. moderate to severe degeneration (Pauli Grade III). In b – d, color-coded parameter value maps are overlaid onto the corresponding morphological images. Histological sections are stained with Hematoxylin-Eosin (e1) and Safranin O (e2).Conclusion:Meniscus functionality may be visualized using serial quantitative MRI mapping techniques. T1ρ may provide an imaging biomarker of relevant intra-tissue adaptations that seem to be associated with histological degeneration. The perspective evaluation of meniscus functionality may be indicative of incipient or manifest load transmission failure to the adjacent cartilage layer.Disclosure of Interests:Philipp Sewerin Grant/research support from: AbbVie Deutschland GmbH & Co. KGBristol-Myers Squibb Celgene GmbHLilly Deutschland GmbHNovartis Pharma GmbH Pfizer Deutschland GmbHRheumazentrum Rhein-Ruhr, Consultant of: AMGEN GmbH AbbVie Deutschland GmbH & Co. KG Biogen GmbHBristol-Myers Squibb Celgene GmbH Chugai Pharma arketing Ltd. / Chugai Europe GmbHHexal Pharma Janssen-CilagGmbH Johnson & Johnson Deutschland GmbHLilly Deutschland GmbH / Lilly Europe / Lilly Global Novartis Pharma GmbH Pfizer Deutschland GmbH Roche Pharma Rheumazentrum Rhein-Ruhr Sanofi-Genzyme Deutschland GmbH Swedish Orphan Biovitrum GmbH UCB Pharma GmbH, Speakers bureau: AMGEN GmbH AbbVie Deutschland GmbH & Co. KG Biogen GmbHBristol-Myers Squibb Celgene GmbH Chugai Pharma arketing Ltd. / Chugai Europe GmbHHexal Pharma Janssen-CilagGmbH Johnson & Johnson Deutschland GmbHLilly Deutschland GmbH / Lilly Europe / Lilly Global Novartis Pharma GmbH Pfizer Deutschland GmbH Roche Pharma Rheumazentrum Rhein-Ruhr Sanofi-Genzyme Deutschland GmbH Swedish Orphan Biovitrum GmbH UCB Pharma GmbH, Lisa Dötsch: None declared, Daniel Truhm: None declared, Daniel Abrar: None declared, Sven Nebelung: None declared

Scientific reports 9, 7172 (2019). doi:10.1038/s41598-019-43389-y, Published by Macmillan Publishers Limited, part of Springer Nature, [London]

Objectives Improved fixation techniques with optional use of bone cements for implant augmentation have been developed to enhance stability and reduce complication rates after osteosynthesis of femoral neck fractures. This biomechanical study aimed to evaluate the effect of cement augmentation on implant anchorage and overall performance of screw-anchor fixation systems in unstable femoral neck fractures. Methods Ten pairs of human cadaveric femora were used to create standardized femoral neck fractures (Pauwels type 3 fractures; AO/OTA 31-B2) with comminution and were fixed by means of a rotationally stable screw-anchor (RoSA) system. The specimens were assigned pairwise to two groups and either augmented with PMMA-based cement (Group 1, augmented) or left without such augmentation (Group 2, control). Biomechanical testing, simulating physiological loading at four distinct load levels, was performed over 10.000 cycles for each level with the use of a multidimensional force-transducer system. Data was analysed by means of motion tracking. Results Stiffness, femoral head rotation, implant migration, femoral neck shortening, and failure load did not differ significantly between the two groups (p ≥ .10). For both groups, the main failure type was dislocation in the frontal plane with consecutive varus collapse). In the cement-augmented specimens, implant migration and femoral neck shortening were significantly dependent on bone mineral density (BMD), with higher values in osteoporotic bones. There was a correlation between failure load and BMD in cement-augmented specimens. Conclusion In screw-anchor fixation of unstable femoral neck fractures, bone-cement augmentation seems to show no additional advantages in regard to stiffness, rotational stability, implant migration, resistance to fracture displacement, femoral neck shortening or failure load.

BioMed research international 2018, 9460456 (2018). doi:10.1155/2018/9460456, Published by Hindawi, New York [u.a.]

Osteoarthritis (OA) is the most common chronic disease of our joints, manifested by a dynamically increasing degeneration of hyaline articular cartilage (AC). While currently no therapy can reverse this process, the few available treatment options are hampered by the inability of early diagnosis. Loss of cartilage surface, or extracellular matrix (ECM), integrity is considered the earliest sign of OA. Despite the increasing number of imaging modalities surprisingly few imaging biomarkers exist. In this narrative review, recent developments in optical coherence tomography are critically evaluated for their potential to assess different aspects of AC quality as biomarkers of OA. Special attention is paid to imaging surface irregularities, ECM organization and the evaluation of posttraumatic injuries by light-based modalities.

Einleitung: Ziele von multidisziplinaren Therapieansatzen nach Einsatz einer Kniegelenksendoprothese (TEP) sind: Senkung postoperativer Komplikationen, fruhe Wiederherstellung der Funktionsfahigkeit, schnellere Rekonvaleszenz, zugigere Wiedereingliederung in den Alltag und Kostenreduktion. Die Fast-Track-Rehabilitation als multidisziplinares Rehabilitationskonzept versucht durch Optimierung des perioperativen Settings insbesondere die Verweildauer im Akutkrankenhaus zu senken, eine fruhfunktionelle Verbesserung zu erreichen und Kosten zu sparen. Methode: Es erfolgte eine Literaturrecherche fur den Zeitraum 1960–2013 zu den Stichwortern: „rehabilitation“, „training“, „physiotherapy“, „physical therapy“, „recovery“, „exercise program“, „knee surgery“, „TKA“, „total knee replacement“, „arthroplasty“, „intensive“, „multidisciplinary“, „accelerated“, „rapid“ oder „fast track“. Eingeschlossen wurden nur prospektive, randomisierte Studien und Metaanalysen. Zusatzlich wurde eine postalische Umfrage in den orthopadischen Rehabilitationskliniken Nordrhein-Westfalens zur Erfassung der Versorgungsrealitat durchgefuhrt. Ergebnisse: Insgesamt wurden 729 Artikel identifiziert; 11 Studien wurden eingeschlossen. Durch Anwendung eines Fast-Track-Konzepts konnen die Verweildauer signifikant verkurzt und Kosten gesenkt werden. Anhand der Studienlage kann eine Verbesserung des kurz- bis mittelfristigen klinischen Outcomes angenommen werden, ohne eine signifikante Verbesserung der klinischen Langzeitergebnisse. Die Ergebnisse der postalischen Umfrage zeigen, dass sich Patienten bei Rehaeintritt in einem reduzierten Allgemeinzustand befinden und die Gehfahigkeit sowie die Bewegungsausmase des Kniegelenks eingeschrankt sind. Schlussfolgerungen: Die Anwendung einer Fast-Track-Rehabilitation ermoglicht eine Reduktion der mittleren Verweildauer im Krankenhaus und fuhrt zu Kostenersparnissen. Zusatzlich bestehen Hinweise, dass sie den korperlichen Zustand des Patienten zu Beginn der Rehabilitation verbessern kann.

Optical Coherence Tomography (OCT) is an evolving imaging technology allowing non-destructive imaging of cartilage tissue at near-histological resolution. This study investigated the diagnostic value of real time 3-D OCT in comparison to conventional 2-D OCT in the comprehensive grading of human cartilage degeneration. Fifty-three human osteochondral samples were obtained from eight total knee arthroplasties. OCT imaging was performed by either obtaining a single two-dimensional cross-sectional image (2-D OCT) or by collecting 100 consecutive parallel 2-D OCT images to generate a volumetric data set of 8 × 8 mm (3-D OCT). OCT images were assessed qualitatively according to a modified version of the DJD classification and quantitatively by algorithm-based evaluation of surface irregularity, tissue homogeneity, and signal attenuation. Samples were graded according to the Outerbridge classification and statistically analyzed by one-way ANOVA, Kruskal Wallis and Tukey's or Dunn's post-hoc tests. Overall, the generation of 3-D volumetric datasets and their multiple reconstructions such as rendering, surface topography, parametric, and cross-sectional views proved to be of potential diagnostic value. With increasing distance to the mid-sagittal plane and increasing degeneration, score deviations increased, too. In conclusion, 3-D imaging of cartilage with image analysis algorithms adds considerable potential diagnostic value to conventional OCT diagnostics.

Posttraumatic osteoarthritis constitutes a major cause of disability in our increasingly elderly population. Unfortunately, current imaging modalities are too insensitive to detect early degenerative changes of this disease. Optical coherence tomography (OCT) is a promising nondestructive imaging technique that allows surface and subsurface imaging of cartilage, at near-histological resolution, and is principally applicablein vivoduring arthroscopy. Thirty-four macroscopically normal human cartilage-bone samples obtained from total joint replacements were subjected to standardized single impactsin vitro(range: 0.25 J to 0.98 J). 3D OCT measurements of impact area and adjacent tissue were performed prior to impaction, directly after impaction, and 1, 4, and 8 days later. OCT images were assessed qualitatively (DJD classification) and quantitatively using established parameters (OII, Optical Irregularity Index; OHI, Optical Homogeneity Index; OAI, Optical Attenuation Index) and compared to corresponding histological sections. WhileOAIandOHIscores were not significantly changed in response to low- or moderate-impact energies, high-impact energies significantly increased mean DJD grades (histology and OCT) andOIIscores. In conclusion, OCT-based parameterization and quantification are able to reliably detect loss of cartilage surface integrity after high-energy traumatic insults and hold potential to be used for clinical screening of early osteoarthritis.

Objective A possible risk factor for premature facet joint degeneration or adjacent segment degeneration after surgical treatment of spine fractures is facet joint violation (FV) during insertion of pedicle screws. The aim of this study was to determine risk factors for FV in the thoracic and lumbar spine after minimally invasive screw insertion or open instrumentation (OI). Methods A retrospective analysis of all patients with spine fractures requiring posterior stabilization was performed. After patients were allocated to the thoracic/lumbar group, FV was defined as an involvement caused by the positioning of a pedicle screw and its severity as determined by computed tomography was assessed by using a customized scoring system. Gender, age, and body mass index as well as segmental facet joint angle and the instrumentation system used (side-loading [SL] vs. top-loading) were considered as individual factors. Results In total, 1099 pedicle screws were evaluated and an FV was identified in 433 instrumentations (39.0%). OI was used in 61.1% (n = 671) and an SL system was inserted in 45.0% (n = 494). In both, the thoracic (odds ratio [OR], 1.663; 95% confidence interval [CI], 1.119–2.472; P = 0.012) and the lumbar spine (OR, 0.494; 95% CI, 0.317–0.771; P = 0.002), OI was associated with a lower risk of FV. The violation rate was significantly higher when using a SL system (thoracic spine: OR, 1.822; 95% CI, 1.163–2.854; P = 0.009; lumbar spine: OR, 0.311; 95% CI, 0.203–0.477; P ≤ 0.001). Conclusions FV is a common complication after thoracic and lumbar spine surgery. Although both, the SL instrumentation and a minimally invasive procedure increases its occurrence, the patient characteristics do not affect the rate of FV.