Experimental guide wire placement for total shoulder arthroplasty in glenoid models: higher precision for patient-specific aiming guides compared to standard technique without learning curve.

BACKGROUND: Patient-specific aiming devices (PSAD) may improve precision and accuracy of glenoid component positioning in total shoulder arthroplasty, especially in degenerative glenoids. The aim of this study was to compare precision and accuracy of guide wire positioning into different glenoid models using a PSAD versus a standard guide. METHODS: Three experienced shoulder surgeons inserted 2.5 mm K-wires into polyurethane cast glenoid models of type Walch A, B and C (in total 180 models). Every surgeon placed guide wires into 10 glenoids of each type with a standard guide by DePuy Synthes in group (I) and with a PSAD in group (II). Deviation from planned version, inclination and entry point was measured, as well as investigation of a possible learning curve. RESULTS: Maximal deviation in version in B- and C-glenoids in (I) was 20.3° versus 4.8° in (II) (p < 0.001) and in inclination was 20.0° in (I) versus 3.7° in (II) (p < 0.001). For B-glenoid, more than 50% of the guide wires in (I) had a version deviation between 11.9° and 20.3° compared to ≤ 2.2° in (II) (p < 0.001). 50% of B- and C-glenoids in (I) showed a median inclination deviation of 4.6° (0.0°-20.0°; p < 0.001) versus 1.8° (0.0°-4.0°; p < 0.001) in (II). Deviation from the entry point was always less than 5.0 mm when using PSAD compared to a maximum of 7.7 mm with the standard guide and was most pronounced in type C (p < 0.001). CONCLUSION: PSAD enhance precision and accuracy of guide wire placement particularly for deformed B and C type glenoids compared to a standard guide in vitro. There was no learning curve for PSAD. However, findings of this study cannot be directly translated to the clinical reality and require further corroboration.

The Diagnostic Arthroscopy Skill Score (DASS): a reliable and suitable assessment tool for arthroscopic skill training.

PURPOSE: To develop and validate a novel score to more objectively assess the performance of diagnostic knee arthroscopy using a simulator. METHODS: A Diagnostic Arthroscopy Skill Score (DASS) was developed by ten AGA (AGA-Society for Arthroscopy and Joint-Surgery) instructors for the assessment of arthroscopic skills. DASS consists of two parts: the evaluation of standardized diagnostic knee arthroscopy (DASSpart1) and the evaluation of manual dexterity, including ambidexterity and triangulation, using objective measurement parameters (DASSpart2). Content validity was determined by the Delphi method. One hundred and eleven videos of diagnostic knee arthroscopies were recorded during simulator training courses and evaluated by six specially trained instructors using DASS. Construct validity, measurement error calculated by the minimum detectable change (MDC), internal consistency using Cronbach's alpha and interrater and intrarater reliability were assessed. The Bland-Altman method was used to calculate the intrarater agreement. RESULTS: Six skill domains were identified and evaluated for each knee compartment. DASS, DASSpart1, and DASSpart2 showed construct validity, with experts achieving significantly higher scores than competents and novices. MDC was 4.5 ± 1.7 points for DASSpart1. There was high internal consistency for all domains in each compartment from 0.78 to 0.86. The interrater reliability showed high agreement between the six raters (ICC = 0.94). The evaluation of intrarater reliability demonstrated good and excellent agreement for five raters (ICC > 0.80) and moderate agreement for one rater (ICC = 0.68). The Bland-Altman comparison showed no difference between the first and second evaluations in five out of six raters. Precision, estimated by the regression analysis and comparison with the method of Bland and Altman, was excellent for four raters and moderate for two raters. CONCLUSIONS: The results of this study indicate good validity and reliability of DASS for the assessment of the surgical performance of diagnostic knee arthroscopy during simulator training. Standardized training is recommended before arthroscopy surgery is considered in patients. LEVEL OF EVIDENCE: II.

Ten hours of simulator training in arthroscopy are insufficient to reach the target level based on the Diagnostic Arthroscopic Skill Score.

PURPOSE: Simulator arthroscopy training has gained popularity in recent years. However, it remains unclear what level of competency surgeons may achieve in what time frame using virtual training. It was hypothesized that 10 h of training would be sufficient to reach the target level defined by experts based on the Diagnostic Arthroscopic Skill Score (DASS). METHODS: The training concept was developed by ten instructors affiliated with the German-speaking Society of Arthroscopy and Joint Surgery (AGA). The programme teaches the basics of performing arthroscopy; the main focus is on learning and practicing manual skills using a simulator. The training was based on a structured programme of exercises designed to help users reach defined learning goals. Initially, camera posture, horizon adjustment and control of the direction of view were taught in a virtual room. Based on these skills, further training was performed with a knee model. The learning progress was assessed by quantifying the exercise time, camera path length and instrument path length for selected tasks. At the end of the course, the learners' performance in diagnostic arthroscopy was evaluated using DASS. Participants were classified as novice or competent based on the number of arthroscopies performed prior to the assessment. RESULTS: Except for one surgeon, 131 orthopaedic residents and surgeons (29 women, 102 men) who participated in the seven courses agreed to anonymous data analysis. Fifty-eight of them were competents with more than ten independently performed arthroscopies, and 73 were novices, with fewer than ten independently performed arthroscopies. There were significant reductions in exercise time, camera path length and instrument path length for all participants after the training, indicating a rapid increase in performance. No difference in camera handling between the dominant and non-dominant sides was found in either group. The competents performed better than the novices in various tasks and achieved significantly better DASS values on the final performance test. CONCLUSIONS: Our data have demonstrated that arthroscopic skills can be taught effectively on a simulator, but a 10-h course is not sufficient to reach the target level set by experienced arthroscopists. However, learning progress can be monitored more objectively during simulator training than in the operating room, and simulation may partially replace the current practice of arthroscopic training. LEVEL OF EVIDENCE: III.

Laxity measurement of internal knee rotation after primary anterior cruciate ligament rupture versus rerupture.

PURPOSE: The aim of the current study was to objectify the rotational laxity after primary anterior cruciate ligament (ACL) rupture and rerupture after ACL reconstruction by instrumented measurement. It was hypothesized that knees with recurrent instability feature a higher internal rotation laxity as compared to knees with a primary rupture of the native ACL. STUDY DESIGN: Cross-sectional study, Level of evidence III. METHODS: In a clinical cross-sectional study successive patients with primary ACL rupture and rerupture after ACL reconstruction were evaluated clinically and by instrumented measurement of the rotational and antero-posterior laxity with a validated instrument and the KT1000®, respectively. Clinical examination comprised IKDC 2000 forms, Lysholm Score, and Tegner Activity Scale. Power calculation and statistical analysis were performed (p value < 0.05). RESULTS: 24 patients with primary ACL rupture and 23 patients with ACL rerupture were included. There was no significant side-to-side difference in anterior translation. A side-to side difference of internal rotational laxity ≥ 10° was found significantly more frequent in reruptures (53.6%) compared to primary ruptures (19.4%; p < 0.001). A highly significant relationship between the extent of the pivot-shift phenomenon and side-to-side difference of internal rotation laxity could be demonstrated (p < 0.001). IKDC 2000 subjective revealed significantly better scores in patients with primary ACL tear compared to patients with ACL rerupture (56.4 ± 7.8 vs. 50.8 ± 6.2; p = 0.01). Patients with primary ACL tears scored significantly better on the Tegner Activity Scale (p = 0.02). No significant differences were seen in the Lysholm Score (p = 0.78). CONCLUSION: Patients with ACL rerupture feature significantly higher internal rotation laxity of the knee compared to primary ACL rupture. The extend of rotational laxity can be quantified by instrumented measurements. This can be valuable data for the indication of an anterolateral ligament reconstruction in ACL revision surgery.

Anteversion Angle Measurement in Suspected Torsional Malalignment of the Femur in 3-Dimensional EOS vs Computed Tomography-A Validation Study.

BACKGROUND: Computed tomography (CT) scan is the standard for assessment of femoral torsion. This observational study was conducted to evaluate the comparability of the EOS radiation dose scanning system (EOS imaging, Paris, France) and the CT scan in patients with suspected torsional malalignment of the femur. METHODS: Patients with suspected torsional malalignment of the femur were included in a study for surgical planning. The primary endpoint was to compare the 3-dimensional radiological (EOS) imaging system with the CT scan to determine femoral anteversion (AV) angle. Three independent raters performed measurements. Comparability of CT scan and EOS values was assessed by Pearson correlation, t test, interobserver reliability, and intraobserver reliability (Cronbach alpha). RESULTS: About 34 femora were examined. Interobserver reliability/intraobserver reliability was 0.911 of 0.955 for EOS and 0.934 of 0.934 for CT scan. EOS system revealed an AV angle of 12.2° ± 10.0° (-15.0° to 32.0°). CT examinations showed an AV angle of 12.6° ± 9.2° (-3.2° to 35.6°). About 11 hips featured physiological AV, 14 hips showed decreased AV (<10°) or retroversion (<0°), and 9 hips showed increased AV (>20°). Overall, a strong Pearson correlation of τ = 0.855 and a highly significant correlation in the t test for both methods was seen. In patients with decreased AV, retroversion, or increased AV, Pearson correlation only resulted in a moderate/low correlation of τ = 0.495 and τ = 0.292. The t test showed no significant correlation at malrotation. CONCLUSION: In torsional malalignment, EOS does not have correlation with CT measurements. In contrast to CT scan, EOS allows femoral torsion measurement independent of legs' positioning.

The value of elbow arthroscopy in diagnosing and treatment of radial head fractures.

BACKGROUND: Surgical treatment of radial head fractures is increasingly performed arthroscopically. These fractures often feature concomitant injuries to the elbow joint, which may be under-diagnosed in the radiological examinations. Little is known about the diagnostic value of arthroscopy, the treatment options that arise from arthroscopically assisted fracture fixation and clinical results. We hypothesized that arthroscopy can detect additional concomitant injuries and simultaneously expands the therapeutic options. Therefore aim of this study was to compare arthroscopic and radiologic findings, to assess the distinct arthroscopic procedures and to follow up on the clinical outcomes. METHODS: Twenty patients with radial head fractures were retrospectively included in two study centers. All patients underwent elbow arthroscopy due to at least one of the following suspected concomitant injuries: osteochondral lesions of the humeral capitellum, injuries of the collateral ligaments or loose joint bodies. Preoperative radiological findings were compared to arthroscopic findings. Afterwards, arthroscopic treatment options and clinical outcomes were assessed. RESULTS: Arthroscopic findings led to revision of the classified fracture type in 70% (p = 0.001) when compared to preoperative conventional radiographs (CR) and in 9% (p = 0.598) when compared to computed tomography (CT) or magnetic resonance imaging (MRI). Diagnosis of loose bodies was missed in 60% (p < 0.001) of the CR and in 18% (p = 0.269) of the CT/MRI scans. Osteochondral lesions were not identified in 94% (p < 0.001) of the CR and in 27% (p = 0.17) of the CT/MRI scans. Percutaneous screw fixation was performed in 65% and partial radial head resection in 10%. Arthroscopy revealed elbow instability in 35%, leading to lateral collateral ligament reconstruction. After a mean follow up of 41.4 ± 3.4 months functional outcome was excellent in all cases (DASH-Score 0.6 ± 0.8; MEPI-Score 98.5 ± 2.4; OES-Score 47.3 ± 1.1). CONCLUSIONS: Elbow arthroscopy has a significant diagnostic value in radial head fractures when compared to standard radiological imaging. Although statistically not significant, arthroscopy also revealed concomitant injuries in patients that presented with an uneventful MRI/CT. Furthermore, all intraarticular findings could be treated arthroscopically allowing for excellent functional outcomes. TRIAL REGISTRATION: Institutional Review Board University of Munich (LMU), Trial Number 507-14.

Screw-tip augmentation versus standard locked plating of displaced proximal humeral fractures: a retrospective comparative cohort study.

BACKGROUND: This study compared the clinical and radiologic outcomes of screw tip-augmented locking plate osteosynthesis vs. standard locked plating in elderly patients with displaced proximal humeral fractures. METHODS: Of the 94 patients older than 65 years with displaced proximal humeral fractures, 55 underwent fixation with a locking plate only whereas 39 underwent fixation using a locking plate with fluoroscopy-controlled polymethyl methacrylate augmentation of screw tips. RESULTS: At 2 years' follow-up, the locking plate-only group showed a mean Constant score (CS) of 62.6 ± 17.4 points, mean CS as a percentage of the uninjured side of 78.2% ± 18.9%, and mean age- and sex-adjusted CS of 72.4 ± 20.5 points. Among the 39 patients who underwent locked plating with polymethyl methacrylate augmentation of screw tips, the mean CS was 63.7 ± 18.5 points (P = .28), the mean CS as a percentage of the uninjured side was 79.5% ± 20.4% (P = .36), and the mean age- and sex-adjusted CS was 76.8 ± 26.2 points (P = .11). The mean Disabilities of the Arm, Shoulder and Hand score was 26.4 ± 21.3 in the locking plate-only group compared with 23.6 ± 19.2 in the group with screw tip-augmented locking plate osteosynthesis (P = .41). The overall complication rate was 16.3% in the locking plate-only group compared with 12.8% in the group with screw tip-augmented osteosynthesis (P = .86); loss of fixation occurred in 10.9% vs. 5.1% (P = .74). The follow-up rate was 81%. CONCLUSIONS: Loss of fixation was less frequent when augmentation of screw tips was performed; however, at the 2-year follow-up, the clinical and radiologic outcomes were not significantly different compared with standard locked plating without augmentation.

Augmentation of plate osteosynthesis for proximal humeral fractures: a systematic review of current biomechanical and clinical studies.

INTRODUCTION: Secondary dislocation due to loss of fixation is the most common complication after plate fixation of proximal humeral fractures. A wide range of different techniques for augmentation has been described to improve the primary and secondary stability. Nevertheless, comparative analyses on the specific advantages and limitations are missing. Therefore, the aim of the present article was to systematically review and evaluate the current biomechanical and clinical studies. MATERIALS AND METHODS: The databases of PubMed and EMBASE were comprehensively searched for studies on augmentation techniques for proximal humeral fractures using defined search terms. Subsequently, all articles identified were screened for eligibility and subdivided in either clinical or biomechanical studies. Furthermore, the level of evidence and study quality were assessed according the Oxford Centre for Evidence-Based Medicine and the Coleman Methodology Score, respectively. RESULTS: Out of 2788, 15 biomechanical and 30 clinical studies were included. The most common techniques were structural allogenic or autologous bone grafting to enhance the medial support, metaphyseal void filling utilizing synthetic bone substitutes or bone grafts, and screw-tip augmentation with bone cement. Biomechanical data were available for structural bone grafting to enhance the medial support, void filling with synthetic bone substitutes, as well as for screw-tip augmentation. Clinical evidence ranged from level II-IV and study quality was 26-70/100 points. Only one clinical study was found investigating screw-tip augmentation. All studies included revealed that any kind of augmentation positively enhances mechanical stability, reduces the rate of secondary dislocation, and improves patients' clinical outcome. None of the studies showed relevant augmentation-associated complication rates. CONCLUSIONS: Augmentation of plate fixation for proximal humeral fractures seems to be a reliable and safe procedure. All common techniques mechanically increase the constructs' stability. Clinically evaluated procedures show reduced complication rates and improved patient outcomes. Augmentation techniques seem to have the highest significance in situations of reduced bone mineral density and in high-risk fractures, such as 4-part fractures. However, more high-quality and comparative clinical trials are needed to give evidence-based treatment recommendations.

Immunohistochemical examination in arthrofibrosis of the knee joint.

INTRODUCTION: Arthrofibrosis (AF) is the result of increased cell proliferation and synthesis of matrix proteins (collagen I, III, and VI). Especially after invasive knee surgery, e.g., ligament reconstruction or knee replacement, abnormal fibroblast proliferation with pathological periarticular fibrosis can be observed leading to severely limited joint motion. The pathogenesis of AF is currently not fully understood. The present work aims to determine pathogenic factors. MATERIALS AND METHODS: A descriptive, histological and immunohistochemical comparative study was performed on tissue samples of 14 consecutive patients undergoing arthrolysis for joint stiffness due to AF. Seven human autopsy specimens served as control. Samples were stained for expression of relevant markers such as CD68, α-smooth muscle actin (ASMA), beta-catenin, BMP-2 and examined for the histological grade of AF (cell-rich versus cell-poor) and compared to a control. Furthermore, a microscopic evaluation of the samples for cell differentiation and number was performed. RESULTS: Tissue sections of cell-rich fibrosis showed a significantly higher expression of CD68 compared to the control with less than 10% of CD68 positive cells (p = 0.002). In cell-poor fibrosis no statistically significant difference was obvious (p = 0.228). Expression of ASMA in synovia, vessels, cell-rich and cell-poor fibrosis showed median values of 2.00 in the AF group and 1.75 in the control. Both groups differed significantly (p = 0.003). AF tissue showed a significantly difference in expression of ß-catenin (p < 0.001) compared to the control. The overall difference between AF and control group in expression of BMP-2 was also statistically significant (p = 0.002). CONCLUSIONS: Expression of CD68, ASMA, beta-catenin and BMP-2 is significantly increased in AF tissue samples. Based on presented findings, histological evaluation and immunohistochemical assessment of CD68, ASMA, ß-catenin and BMP-2 expression may proof useful to diagnose AF and to analyze AF activity.

Concomitant glenohumeral injuries in Neer type II distal clavicle fractures.

BACKGROUND: To identify the prevalence of concomitant glenohumeral injuries in surgically treated Neer type II distal clavicle fractures and relate its clinical importance. METHODS: Between 11/2011 and 11/2015 41 patients, suffering from a displaced and unstable distal clavicle fracture were included. 20 patients (group 1) received surgical treatment by means of plate osteosynthesis in combination with an arthroscopically assisted coraco-clavicular ligament augmentation. In group 2 (n = 21 patients) the fracture was treated by hooked plating solely, and diagnostic arthroscopy was conducted during hardware retrieval after the fracture had healed. All arthroscopies were performed in a standardized fashion, images were blinded retrospectively, and evaluated by two independent investigators. RESULTS: In total, concomitant glenohumeral pathologies were found in 26.8% of cases (41 patients, mean age 43.6 ± 16.6 years). In Group 1 (n = 20, arthroscopically assisted fracture treatment) the prevalence was 25%, in Group 2 (n = 21, diagnostic arthroscopy during implant removal) 28.5% (p = 0.75). Concomitant glenohumeral injuries included Labrum- and SLAP-tears, partial and full thickness rotator cuff tears as well as lesions to the biceps pulley system. Concomitant injuries were addressed in 2 patients of group 1 (10%, 2× labrum repair) and in 3 patients of group 2 (14.3%, of Group 2 (2× arthroscopic cuff repair of full thickness tear, 1× subpectoral biceps tenodesis in an type IV SLAP lesion, p = 0.68). CONCLUSION: The present study could clarify the acute and for the first time mid-term implication and clinical relevance of concomitant glenohumeral injuries. They have been observed in averaged 27% of Neer type II distal clavicle fractures at these two times. However, the findings of this study show that not all concomitant lesions remain symptomatic. While lesions are still present after fracture healing, it's treatment may be depicted upon symptoms at the time of implant removal. In turn, early diagnosis and treatment of concomitant injuries seems reasonable, as untreated injuries can remain symptomatic for more than 6 months after the fracture and recovery may be delayed.

Structured reporting of MRI of the shoulder - improvement of report quality?

OBJECTIVES: To evaluate the effect of structured reports (SRs) in comparison to non-structured narrative free text (NRs) shoulder MRI reports and potential effects of both types of reporting on completeness, readability, linguistic quality and referring surgeons' satisfaction. METHODS: Thirty patients after trauma or with suspected degenerative changes of the shoulder were included in this study (2012-2015). All patients underwent shoulder MRI for further assessment and possible surgical planning. NRs were generated during clinical routine. Corresponding SRs were created using a dedicated template. All 60 reports were evaluated by two experienced orthopaedic shoulder surgeons using a questionnaire that included eight questions. RESULTS: Eighty per cent of the SRs were fully complete without any missing key features whereas only 45% of the NRs were fully complete (p < 0.001). The extraction of information was regarded to be easy in 92% of the SRs and 63% of the NRs. The overall quality of the SRs was rated better than that of the NRs (p < 0.001). CONCLUSIONS: Structured reporting of shoulder MRI improves the readability as well as the linguistic quality of radiological reports, and potentially leads to a higher satisfaction of referring physicians. KEY POINTS: • Structured MRI reports of the shoulder improve readability. • Structured reporting facilitates information extraction. • Referring physicians prefer structured reports to narrative free text reports. • Structured MRI reports of the shoulder can reduce radiologist re-consultations.

Operative treatment of 2-part surgical neck fractures of the proximal humerus (AO 11-A3) in the elderly: Cement augmented locking plate Philos™ vs. proximal humerus nail MultiLoc®.

BACKGROUND: Proximal humeral fractures are with an incidence of 4-5 % the third most common fractures in the elderly. In 20 % of humeral fractures there is an indication for surgical treatment according to the modified Neer-Criteria. A secondary varus dislocation of the head fragment and cutting-out are the most common complications of angle stable locking plates in AO11-A3 fractures of the elderly. One possibility to increase the stability of the screw-bone-interface is the cement augmentation of the screw tips. A second is the use of a multiplanar angle stablentramedullary nail that might provide better biomechanical properties after fixation of 2-part-fractures. A comparison of these two treatment options augmented locking plate versus multiplanar angle stable locking nail in 2-part surgical neck fractures of the proximal humerus has not been carried out up to now. METHODS/DESIGN: Forty patients (female/male, ≥60 years or female postmenopausal) with a 2-part-fracture of the proximal humerus (AO type 11-A3) will be randomized to either to augmented plate fixation group (PhilosAugment) or to multiplanar intramedullary nail group (MultiLoc). Outcome parameters are Disabilities of the Shoulder, Arm and Hand-Score (DASH) Constant Score (CS), American Shoulder and Elbow Score (ASES), Oxford Shoulder Score (OSS), Range of motion (ROM) and Short Form 36 (SF-36) after 3 weeks, 6 weeks, 3 months, 6 months, 12 and 24 months. DISCUSSION: Because of the lack of clinical studies that compare cement augmented locking plates with multiplanar humeral nail systems after 2-part surgical neck fractures of the proximal humerus, the decision of surgical method currently depends only on surgeons preference. Because only a randomized clinical trial (RCT) can sufficiently answer the question if one treatment option provides advantages compared to the other method we are planning to perform a RCT. TRIAL REGISTRATION: Clinical Trial ( NCT02609906 ), November 18, 2015, registered retrospectively.

Complications of locked plating for proximal humeral fractures-are we getting any better?

BACKGROUND: Complication rates reported after locking plate fixation of proximal humeral fractures still range up to 40%. Whether modifications of surgical techniques, use of primary shoulder arthroplasty, or a fracture-specific management resulted in decreased complication rates during recent years remains unclear. Therefore, the aim of this long-term observation study was to analyze the incidence of complications and revision surgery after locked plating. METHODS: Between February 2002 and December 2013, 788 patients (aged 67.4 ± 17.3 years) with displaced proximal humeral fractures were treated with locking plate, primary hemiarthroplasty (HA), or reverse shoulder arthroplasty (RSA). Standardized follow-up included radiographs at 1 day, 6 weeks, and 3, 6, and 12 months. Complications and unplanned revision surgery were prospectively recorded over the complete follow-up. RESULTS: Of 788 patients, 646 (82%) were treated with locking plate, 82 (10.4%) with HA, and 60 (7.6%) with RSA. Mean follow-up was 14.8 ± 3.8 months. The mean complication rate associated with locked plating was 12.8%, and revision surgery was necessary in 11.6%. Within the last 5 years, the loss of fixation rate markedly decreased from 14.3% to 4.8%; simultaneously, an increased use of RSA was observed. CONCLUSION: The overall complication rate of locking plate osteosynthesis for proximal humeral fractures has been decreasing considerably within the last years. Among others, this might be due to an increased use of primary RSA for complex fracture types. In addition to a precise surgical technique, choosing the adequate treatment for each individual fracture to avoid complications and revision surgery is of utmost importance.

Mesenchymal stem cells from osteoporotic patients reveal reduced migration and invasion upon stimulation with BMP-2 or BMP-7.

Fractures to the osteoporotic bone feature a delay in callus formation and reduced enchondral ossification. Human mesenchymal stem cells (hMSC), the cellular source of fracture healing, are recruited to the fracture site by cytokines, such as BMP-2 and BMP-7. Aim of the study was to scrutinize hMSC for osteoporosis associated alterations in BMP mediated migration and invasion as well as in extracellular matrix (ECM) binding integrin expression. HMSC were isolated from 18 healthy or osteoporotic donors. Migration was assessed using a collagen IV coated micro-slide linear gradient chamber and time-lapse microscopy. Invasion was analyzed utilizing an ECM coated transmembrane invasion assay. Quantitative real-time RT PCR was performed for the ECM binding integrins α1, α2, α3, α4, α5, α11, αv and ß1. HMSC from osteoporotic patients showed a significant increase of migration upon BMP-2 or FCS stimulation, as well as a significant increase of invasion upon BMP-2, BMP-7 or FCS stimulation. Nevertheless, the migration and invasion capacity was significantly decreased compared to healthy controls. Out of all integrins analyzed, collagen binding integrin α2 was significantly downregulated in hMSC from osteoporotic patients. In conclusion, we here demonstrate for the first time osteoporosis associated alterations in BMP mediated hMSC recruitment. These findings may underlie the reduced healing of osteoporotic fractures. Nevertheless, the maintained migration and invasion response upon BMP stimulation illustrates the therapeutic potential of these clinically approved substances in the treatment of osteoporotic fractures. Another therapeutic target may be the downregulation of the collagen binding integrin α2 in hMSC from osteoporotic patients.

Overexpression of dnIKK in mesenchymal stem cells leads to increased migration and decreased invasion upon TNFα stimulation.

IκB kinase 2 (IKK-2) mediates tumor necrosis-factor α (TNFα) induced invasion of human mesenchymal stem cell (hMSC) to sites of tissue injury. Suppressing IKK-2 activity leads to reduced expression of proteolytic enzymes and impaired invasive capacity. In order to further reveal mechanisms of hMSC recruitment, we here aimed to analyse the impact of IKK-2 on two-dimensional migration upon TNFα stimulation in contrast to three-dimensional invasion. An immortalized hMSC line (SCP-1) was transduced with a dominant-negative mutant of IκB kinase 2 (SCP-1 dnIKK). Migration was assessed using a linear-gradient chemotaxis chambers by time-lapse analysis. Invasive capacity through human extracellular matrix was analysed using transwell invasion assays. RT-PCR confirmed increased IKK-2 expression levels in SCP-1 dnIKK cells, while TNFα receptor I and II expression was not altered. Invasion upon TNFα stimulation was significantly reduced by 78% in SCP-1 dnIKK. In contrast, migration was significantly increased, represented by a 60% elevated forward migration index and a 2.1-fold higher mean dislocation of the center of mass towards TNFα. In conclusion, our data confirms the impact of IKK-2 in TNFα dependent hMSC recruitment. Interestingly, reducing IKK-2 function increases two-dimensional migration towards TNFα, while invasive capacity is impaired. These findings contribute to a deeper understanding of MSC's biological properties orchestrating the complex processes of stem cell recruitment and homing.

Mesenchymal stem cells from osteoporotic patients feature impaired signal transduction but sustained osteoinduction in response to BMP-2 stimulation.

Osteoporotic fractures show reduced callus formation and delayed bone healing. Cellular sources of fracture healing are mesenchymal stem cells (MSC) that differentiate into osteoblasts by stimulation with osteoinductive cytokines, such as BMP-2. We hypothesized that impaired signal transduction and reduced osteogenic differentiation capacity in response to BMP-2 may underlie the delayed fracture healing. Therefore, MSC were isolated from femoral heads of healthy and osteoporotic patients. Grouping was carried out by bone mineral densitometry in an age-matched manner. MSC were stimulated with BMP-2. Signal transduction was assessed by western blotting of pSMAD1/5/8 and pERK1/2 as well as by quantitative RT-PCR of Runx-2, Dlx5, and Osteocalcin. Osteogenic differentiation was assessed by quantifying Alizarin Red staining. Osteoporotic MSC featured an accurate phosphorylation pattern of SMAD1/5/8 but a significantly reduced activation of ERK1/2 by BMP-2 stimulation. Furthermore, osteoporotic MSC showed significantly reduced basal expression levels of Runx-2 and Dlx5. However, Runx-2, Dlx5, and Osteocalcin expression showed adequate up-regulation due to BMP-2 stimulation. The global osteogenic differentiation in standard osteogenic differentiation media was reduced in osteoporotic MSC. Nevertheless, osteoporotic MSC were shown to feature an adequate induction of osteogenic differentiation due to BMP-2 stimulation. Taken together, we here demonstrate osteoporosis associated alterations in BMP-2 signaling but sustained specific osteogenic differentiation capacity in response to BMP-2. Therefore, BMP-2 may represent a promising therapeutic agent for the treatment of fractures in osteoporotic patients.

Assessment of the Value of Registries in Shoulder Arthroplasty Using Reverse Arthroplasty as an Example. / Die Wertigkeit von Endoprothesenregistern in der Schulterendoprothetik am Beispiel der inversen Endoprothese.

INTRODUCTION: As a consequence of the Swedish model, endoprosthesis registers have become increasingly important worldwide. Due to the increasing number of joint replacements at the shoulder, these are being increasingly included in the register databases - in addition to interventions at the hip and knee joint. In this study, the value of endoprosthesis registers is investigated, using the example of shoulder endoprosthetics and including a comparison with clinical studies. MATERIAL AND METHODS: The annual reports of 32 different endoprosthesis registers with data on hip, knee and/or shoulder arthroplasty were analysed. The number of operations and demographic patient data for all areas of endoprosthetics were examined. In addition, a more detailed consideration of variables such as the primary diagnosis, the cause of the revision, the revision rate depending on risk factors and patient-reported outcome measures (PROM scores) was carried out exclusively for the shoulder joint endoprostheses. Using the example of the inverse shoulder prosthesis, clinical studies were compared to registry data with special regard to the revision rate. RESULTS: A total of 20 endoprosthesis registers could be included, 9 of these collected data on shoulder arthroplasty. The main primary diagnoses were osteoarthritis (40.6%), rotator cuff defect arthropathy (30.2%) and fractures (17.6%). The most commonly used shoulder joint endoprosthesis was the inverse prosthesis (47.3%). The proportion of revision surgeries in total shoulder arthroplasty operations was less than 10% in all registers. In addition to the revision rate, the PROM scores were sometimes used in the registers to evaluate the success of the prosthesis. Compared to registry data, clinical studies showed more heterogeneous data with a significantly higher revision rate of over 10% in long-term follow-up - using the example of the inverse shoulder prosthesis. CONCLUSION: Register data are a valuable source of information in shoulder arthroplasty and can make a significant contribution to the quality assurance of endoprosthetic treatments. Compared to clinical studies, they primarily provide data on durability of different endoprosthesis and give lower revision rates. Clinical studies use PROM scores and clinical and radiological examinations to focus only on individual implants and surgical centres on the one hand and much more on the functional results on the other.

Radiological and Clinical Outcomes after Anterior Cervical Discectomy and Fusion (ACDF) with an Innovative 3D Printed Cellular Titanium Cage Filled with Vertebral Bone Marrow.

Objectives: To assess the clinical and radiological outcomes after ACDF with 3D printed cellular titanium cages filled with bone marrow and to compare the clinical and radiological results with the current scientific literature. Methods: ACDF was performed monosegmentally under standardized conditions. X-rays were analyzed to determine the range of motion, fusion rates, and subsidence preoperatively and 3 and 12 months postoperatively. Clinical outcome measurements included neck disability index (NDI), visual analogue scale (VAS) for brachialgia and cervicalgia, and patient satisfaction. Results: 18 patients were included in the study. The mean RoM decreased from 7.7° ± 2.6 preoperatively to 1.7° ± 1.1° after 3 months and 1.8° ± 1.2° 12 months after surgery. The fusion rates were at 94.4% after 3 and 12 months. The mean subsidence was 0.9 mm ± 0.5 mm 3 months postoperatively and 1.1 mm ± 0.5 mm 12 months after surgery. The mean NDI improved significantly from preoperatively to 12 months postoperatively (34.6 ± 6.2 and 3.4 ± 4.1, respectively). The VAS-neck also showed a large improvement from 5.8 ± 2.2 before and 1.3 ± 1.4 12 months after surgery, as did the VAS-arm (6.4 ± 1.5 and 0.9 ± 1.6, respectively). Patient satisfaction was high throughout the follow-up period. Conclusion: ACDF with a 3D printed titanium cage resulted in fast fusion without pathological subsidence. In comparison to other cage materials such as PEEK, the 3D printed titanium cage was noninferior in regard to its fusion rate and clinical results.