Tibial cut is a crucial step in ensuring adequate and appropriate proximal tibial resection for mechanical orientation and axis in total knee replacement. We evolved the concept and technique of Condylar Differential for planned tibial cuts in conventional total knee replacement, which accounts for individual variations and reflects individual mechanical orientation and alignment. We used Condylar Differential in 37 consecutive total knee replacements including valgus knees and severe advanced osteoarthritis. First a vertical line is drawn on digital weight bearing anteroposterior radiograph for mechanical axis of tibia. Then a horizontal line is drawn across and perpendicular to the mechanical axis. The distances between the horizontal line and the lowest reproducible points of articular surfaces of medial and lateral tibial condyles respectively are measured. The difference between two measurements obviously represents Condylar Differential. Condylar Differential, adjusted to the nearest millimetre, is maintained in executing tibial cuts, successively if necessary. Condylar Differential measurement showed a very wide variation, ranging from 8–6 (2 mm) to 10-0 (10 mm). We found that prior measurement of Condylar Differential is a simple, consistent and effective estimate and individualises the tibial cut for optimal templating of tibia. We encountered no problems, adopting this technique, in our series. Condylar Differential contributes to optimal individualised tibial cut in conventional total knee replacement and is a useful alternative to computer navigated option with comparable accuracy in this respect. While we used the technique in digitised radiographs, this technique can also be applied to plain films, allowing for magnification

Background. Mechanics and kinematics of the knee following total knee replacement are related to the mechanics and kinematics of the normal knee. Restoration of neutral alignment is an important factor affecting the long-term results of total knee replacement. Tibial cut is a vital and crucial step in ensuring adequate and appropriate proximal tibial resection, which is essential for mechanical orientation and axis in total knee replacement. Tibial cut must be individually reliable, reproducible, consistent and an accurate predictor of individual anatomical measurements. Conventional tibial cuts of tibia with fixed measurements cannot account for individual variations. While computer navigated total knee replacement serves as a medium to achieve this objective, the technology is not universally applicable for differing reasons. Therefore we evolved the concept and technique of Condylar Differential for planned tibial cuts in conventional total knee replacement, which accounts for individual variations and reflects the individual mechanical orientation and alignment. Methods. We used the Condylar Differential in 37 consecutive total knee replacements. We also applied the technique in valgus knees and severe advanced osteoarthritis. First a vertical line is drawn on the digital weight bearing anteroposterior radiograph for mechanical axis of tibia. Then a horizontal line is drawn across and perpendicular to the mechanical axis of tibia. The distances between the horizontal line and the lowest reproducible points of the articular surfaces of the medial and lateral tibial condyles respectively are measured. The difference between the two measurements obviously represents the Condylar Differential. Condylar Differential, adjusted to the nearest millimeter, is maintained in executing the tibial cuts, if necessary successive cuts. Results. Condylar Differential measurement showed a very wide variation, ranging from 8–6 (2 mm) to 10-0 (10 mm). We found that prior measurement of Condylar Differential is a simple, consistent and effective estimate and individualizes the tibial cut for optimal templating of tibia in total knee replacement. We encountered no problems, adopting this technique, in our consecutive series of total knee replacements. Conclusions. Condylar Differential contributes to optimal individualized tibial cut in conventional total knee replacement and is a useful alternative to computer navigated option with comparable accuracy in this respect. While we used the technique of Condylar Differential in digitized radiographs, this technique can also be applied to plain films, allowing for the magnification

Aim. One of the most accurate and inexpensive tests in detection of prosthetic joint infection (PJI) is synovial fluid white blood cell (WBC) count and differential. Since leukocytes produce many different interleukins (IL) in situation of PJI, we hypothesized that ILs could be even more accurate in detection of PJI. The aim of the study was to test, if the synovial fluid IL-6 level is superior to WBC count and differential in detection of PJI. Methods. Unselected patients undergoing total hip or knee revision surgery were prospectively included. In perioperative assessment phase, WBC count, differential and IL-6 levels of synovial fluid were measured. Patients were labelled as positive or negative according to the predefined cut-off values for IL-6 (230pg/ml) and WBC count with differential (1,7 × 10. 9. WBC/ml with ≥65% of granulocytes). During the surgery, at least 4 intraoperative samples for microbiological and one for histopathological analysis were obtained. PJI was defined as presence of sinus tract, inflammation in histopathological samples, and growth of the same microorganism in at least two or more samples of periprosthetic tissue or synovial fluid. Binary diagnostic test was performed to check the diagnostic strength of both methods in detection of PJI. Results. 49 joints of 48 patients (mean age, 71 years; 53% females) undergoing artificial hip (n = 24) or knee (n = 25) revision surgery were included. 11 joints (22%) were infected. Sensitivity of synovial fluid WBC count with differential was 82%, specificity 97%, accuracy 94%, positive and negative predictive values were 90% and 95%, respectively. Sensitivity of IL-6 level was 73%, specificity 95%, accuracy 90%, positive and negative predictive values were 80% and 92%, respectively. There was a strong statistical agreement between both tests (Kappa value=0.749) and consequently there was no significant difference in detection of PJI comparing both tests (P=0.171). Conclusion. Our study revealed that synovial fluid IL-6 level is not superior to synovial fluid WBC count with differential in detecting PJI

Introduction and Objective. Exosomal miRNA have been shown to regulate many myogenic and osteogenic pathways involved in injury repair and healing. It is also known that rehabilitation and exercise can improve muscle mass and bone growth. The mechanisms by which this occurs in vivo are well studied, but the impact exosomes and their associated miRNA cargo have is unclear. With this knowledge and question in mind, we hypothesized that C2C12 myoblasts subjected to in vitro mechanical stimulus (“exercise”) would exhibit improved exosome production and differentially expressed miRNA cargo when compared to their static (“unexercised”) counterparts. Materials and Methods. C2C12 myoblasts were cultured using the FlexCell FX-5000TT bioreactor. Two exercise regimens were programmed: 1) low intensity regimen (LIR) (0–15% strain at 0.5 Hz for 24 hours) 2) high intensity interval regimen (HIIR) (12–22% strain at 1 Hz for 10 minutes followed by 50 minutes of rest repeated for 24 hours). Unexercised (static) cells were cultured in parallel. Exosomes were isolated using the Invitrogen Total Exosome Isolation Reagent. The Pierce BCA Protein Assay, System Bioscience's ExoELISA-ULTRA CD81 Kit and, SBI's ExoFlow-ONE EV labeling kit were used to confirm and quantify exosome number and protein concentration. The SBI Exo-NGS service was used to perform miRNA sequencing on isolated exosomes. Results. All exercise regimens resulted in increased exosome concentrations as determined by CD81 exosome ELISA and flow-cytometry based exosome quantification. The LIR interestingly produced significantly more exosomes than static and HIIR. Within the exosomes from mechanically stimulated cells, 35 miRNAs were found to be differentially expressed when compared to exosomes from unexercised cells. Interestingly, this significance was only found within exosomes from the HIIR group. Specifically, upon investigation 8 of these miRNAs were found to be involved in myogenic and osteogenic proliferation and differentiation. These results correlate with our previous findings that exosomes from exercised cells improve the proliferation and myogenic differentiation of C2C12 myoblasts. Conclusions. Our results indicate that exercise can be optimized to improve the production and regenerative capacity of exosomes. These results also indicate that exosomes may be intimately involved in systemic health and repair during rehabilitation and exercise. To examine these results in vivo, mouse studies using a crush injury model and exosomes from mechanically stimulated cells are currently planned

Chondrogenic differentiation and cartilage homeostasis requires a high cellular translational capacity to meet the demands for cartilaginous extracellular matrix production. Box C/D and H/ACA snoRNAs guide post-transcriptional 2′-O ribose methylation and pseudouridylation of specific ribosomal RNA (rRNA) nucleotides, respectively. How specific rRNA modifications influence rRNA function is poorly documented, but modifications are thought to tune rRNA folding and interaction with ribosomal proteins, which is critical for ribosome function. We hypothesise that chondrocyte translational capacity is supported by snoRNA-mediated post-transcriptional fine-tuning of rRNAs. ATDC5 progenitor cells were differentiated into the chondrogenic lineage, resembling mature and mineralising chondrocytes after 7 or 14 days, respectively. UBF-1 (rRNA transcription factor), fibrillarin (box C/D methyltransferase) and dyskerin (box H/ACA pseudouridylase) expression displayed highest fold induction at day 5/6 in differentiation. Ribosomal RNA content per cell was increased at day 7, but not at day 14 in differentiation. These data suggest that ribosome biogenesis adapts to the chondrocyte's differentiation status. RNA-Seq of RNA species <200 nt revealed expression of at least 224 individual snoRNAs. Due to initiation of chondrogenic differentiation (Δt0-t7), 21 snoRNAs were differentially expressed (DE; FDRadj-p<0.05, logFC>1or<−1). Mineralization (Δt7-t14) induced DE of 23 snoRNAs. Comparing t0 with t14 resulted in DE of 43 snoRNAs. To anticipate on the biological relevance of DE snoRNAs, their rRNA target nucleotides were plotted in 18S, 5.8S and 28S rRNA secondary structures. This revealed that DE snoRNAs, amongst others, target nucleotide modifications in the 28S peptidyl transferase center and the 18S decoding center (DC). Snora40 was DE, targeting helix 27/18S rRNA. Helix 27 controls DC function. Helix 68 of 28S rRNA is part of the ribosome's E-site, therefore, DE snord36c and snora31 (targeting helix 68) could potentially fine-tune the translation mechanism. As a final example we found snord46 to be DE (target: helix 69/28S rRNA). Mutations in helix 69 have been shown to severely affect cell viability. Our data show that increased demand for translational capacity during chondrogenic differentiation is associated with differential expression of snoRNAs, potentially controlling ribosome fidelity via site-specific rRNA-modifications. These data enable us to determine the role of individual snoRNAs in tuning the chondrocyte's translational properties and current efforts focus on confirming site-specific rRNA-modifications and determine their biological relevance

Cut-off values with highest sensitivity and specificity for the synovial fluid white cell and differential count will facilitate the accurate diagnosis of infection in total knee (TKR) and total hip replacement (THR). All patients undergoing revision TKR or THR for suspected prosthetic joint infection between 2009 and 2011 at two hospitals were identified. A total of 75 patients were included with a mean age of 70.3 years (38 to 89). Synovial fluid was aspirated pre-operatively and peri-prosthetic tissue samples were taken intra-operatively for histological and microbiological examination. Receiver operating characteristic (ROC) plots were constructed for white cell and differential counts in aspirated fluid. The optimal cut-off for TKR and THR was 1590 white cells/µl and 65% neutrophilia. The white cell count cut-off value identified for THR was notably lower than previously quoted in the literature. A cut-off value for white cell count in synovial aspirate in suspected prosthetic joint infection of between 1100 and 1700 white cells/µl is likely to be applicable to both THR and TKR. Cite this article: Bone Joint J 2013;95-B:554–7

In response to the COVID-19 pandemic public health measures were implemented to limit virus spread. After initial implementation of a province-wide lockdown (Stage 1), there followed a sequential ease of restrictions through Stages 2 and 3 over a 6-month period from March to September 2020 (Table 1). We aimed to determine the impact of COVID-19 public health measures on the epidemiology of operative paediatric orthopaedic trauma and to determine differential effects of each stage of lockdown. A retrospective cohort study was performed comparing all emergency department (ED) visits for musculoskeletal trauma and operatively treated orthopaedic trauma cases at a Level-1 paediatric trauma center during Mar-Sep 2020 (pandemic), compared with Mar-Sep 2019 (pre-pandemic). All operative cases were analyzed based on injury severity, mechanism of injury (MOI) and anatomic location (AL). Comparisons between groups were assessed using chi-square testing for categorical variables, and student t-tests and Fisher's exact tests for continuous variables. During the pandemic period, ED visits for orthopaedic trauma decreased compared to pre-pandemic levels by 23% (1370 vs 1790 patients) and operative treatment decreased by 28% (283 vs 391 patients). There was a significant decrease in the number of operative cases per day in lockdown Stage 1 (1.25 pandemic vs 1.90 pre- pandemic; p < 0 .001) and Stage 2 (1.65 pandemic vs 3.03 pre-pandemic; p< 0.001) but no difference in operative case number during Stage 3 (2.18 pandemic vs 2.45 pre-pandemic; p=0.35). Significant differences were found in MOI and AL during Stage 1 (p < 0 .001) and Stage 2 (p < 0 .001) compared to pre-pandemic. During Stage 1 and 2, playground injuries decreased by 95% and 82%, respectively; sports injuries decreased by 79% and 13%, and trampoline injuries decreased 44% and 43%, compared to pre-pandemic. However, self-propelled transit injuries (bicycles/skateboards) increased during Stage 1 and Stage 2 by 67% and 28%, respectively compared to pre- pandemic. During lockdown Stage 3 there were no differences in MOI nor AL. There were no significant differences in injury severity in any lockdown stage compared to pre-pandemic. COVID-19 lockdown measures significantly reduced the burden of operative paediatric orthopaedic trauma. Differences in volume, mechanism and pattern of injuries varied by lockdown stage offering evidence of the burden of operative trauma related to specific childhood activities. These findings will assist health systems planning for future pandemics and suggest that improvements in safety of playgrounds and self-propelled transit are important in reducing severe childhood injury requiring operative intervention. For any figures or tables, please contact the authors directly

Abstract. Introduction. It is increasingly evident that synovium may play a larger role in the aetiology of osteoarthritis. We compared gene expression in whole tissue synovial biopsies from end-stage knee osteoarthritis and knee trauma patients with that of their paired explant cultures to determine how accurately cultured cells represent holistic synovial function. Methodology. Synovial tissue biopsies were taken from 16 arthroplasty patients and 8 tibial plateau fracture patients with no osteoarthritis. Pairs of whole tissue fragments were either immediately immersed in RNAlater Stabilisation Solution at 4o C before transfer to -80o C storage until RNA extraction; or weighed, minced and cultured at 500mg tissues/5ml media in a humidified incubator at 37oC, 5% CO2. After sub-culturing total RNA was extracted using RNAeasy Plus Mini Kit with gDNA removal. Following RT-PCR and quality assessment, cDNA was applied to Affymetrix Clariom D microarray gene chips. Bioinformatics analyses were performed. Results. PCA analysis illustrates the clear separation of expression array data from cultured cells compared with their parental whole tissues and no segregation between cells derived from osteoarthritic or trauma tissues. A differentially expressed gene heat map demonstrated the hierarchical independence of cultured cells from their paired sample parental tissues. The biological pathways enriched by these gene expression differences emphasise the activities of macrophages and lymphocytes lost from culture. Conclusion. Adherent synovial cells grown from different knee pathologies lose the expression patterns characteristic of their originating pathology. Interpretation of data needs caution as the cells are not representative of whole synovium

Aims: The goal of this study to compare the clinical outcome of patients with calcaneus fractures differential strategy and non-differential conservative strategy treated. Methods: The study based on the results of treatment of 122 patients with 140 heel bone fractures. Results of only conservative treated 52 patients (54 fractures) in period 1992–1999 were retrospectively evaluated. Results of 70 patients (86 fractures) differential strategy treated in period 1999–2001 were prospectively evaluated. The plain radiographs – that is lateral, antero-posterior, oblique radiographs of the foot, axial and Broden view – and computerized tomography were used for examine patients. In period 1999–2001 the patients were differential strategy treated. All patients were divided in 5 groups: non-displacement fractures (early range of motion), beak type fractures (close reduction internal fixation by cannulated screw), tongue-type fractures (axial reposition axial fixation by Schantz screw), jointdepression and comminuted fractures (ORIF calcaneus bone plate AO). The results were evaluated by own score system in first group in 4 – 8 years period and 1 – 2,5 years period in second group. Results: The results of differential strategy treated patients with heel bone fractures (excellent – 60,9%± 5,9, good – 29,0%± 4,8, fair – 5,8%± 2,4, bad – 4,3%± 2,1) were reliably (p≥95%) better than results in only conservative treated group (excellent – 26,8%±4,7, good – 23,9%±4,5, fair – 23,9%±4,5, bad 25,4%±4,6). Conclusions: This study demonstrates that the differential strategy of treatment allows to reach good results and minimize soft tissue trauma

Aims. The results of kinematic total knee arthroplasty (KTKA) have been reported in terms of limb and component alignment parameters but not in terms of gap laxities and differentials. In kinematic alignment (KA), balance should reflect the asymmetrical balance of the normal knee, not the classic rectangular flexion and extension gaps sought with gap-balanced mechanical axis total knee arthroplasty (MATKA). This paper aims to address the following questions: 1) what factors determine coronal joint congruence as measured on standing radiographs?; 2) is flexion gap asymmetry produced with KA?; 3) does lateral flexion gap laxity affect outcomes?; 4) is lateral flexion gap laxity associated with lateral extension gap laxity?; and 5) can consistent ligament balance be produced without releases?. Patients and Methods. A total of 192 KTKAs completed by a single surgeon using a computer-assisted technique were followed for a mean of 3.5 years (2 to 5). There were 116 male patients (60%) and 76 female patients (40%) with a mean age of 65 years (48 to 88). Outcome measures included intraoperative gap laxity measurements and component positions, as well as joint angles from postoperative three-foot standing radiographs. Patient-reported outcome measures (PROMs) were analyzed in terms of alignment and balance: EuroQol (EQ)-5D visual analogue scale (VAS), Knee Injury and Osteoarthritis Outcome Score (KOOS), KOOS Joint Replacement (JR), and Oxford Knee Score (OKS). Results. Postoperative limb alignment did not affect outcomes. The standing hip-knee-ankle (HKA) angle was the sole positive predictor of the joint line convergence angle (JLCA) (p < 0.001). Increasing lateral flexion gap laxity was consistently associated with better outcomes. Lateral flexion gap laxity did not correlate with HKA angle, the JLCA, or lateral extension gap laxity. Minor releases were required in one third of cases. Conclusion. The standing HKA angle is the primary determinant of the JLCA in KTKA. A rectangular flexion gap is produced in only 11% of cases. Lateral flexion gap laxity is consistently associated with better outcomes and does not affect balance in extension. Minor releases are sometimes required as well, particularly in limbs with larger preoperative deformities. Cite this article: Bone Joint J 2019;101-B:331–339

Although there is still no absolute diagnostic test for infection of the prosthetic joint, the synovial fluid leukocyte count and neutrophil percentage have been reported as having high sensitivity and specificity but to date the cut off values for these tests are not agreed upon. We investigated whether leukocyte count and differential of aspirated joint fluid are valuable tools in the diagnosis of suspected prosthetic joint infection. In 39 patients who underwent revision arthroplasty the cell count and differential of joint aspirates were cross-referenced with culture results and histology to confirm that these were valid tests and to determine cut off values. Cases were identified via the microbiology service of two district general hospitals: 17 patients in whom infection was identified via culture and/or histology results and 19 who were uninfected. Receiver operator characteristic curves were used to determine the correlation between the results of the two tests and to identify a suitable threshold level. For absolute leukocyte count the area under the curve was 0.997 indicating excellent agreement between the tests. A cut off value of 2000 gave a sensitivity of 100% and a specificity of 94%. Differential count had an area under the curve of 0.94. A threshold of 50% had a sensitivity of 100% and a specificity of 77%. Despite the low number of patients this study shows that the leukocyte count and differential of aspirated joint fluid are valuable tools in the diagnosis of suspected prosthetic joint infection

Summary. The presence or absence of crimp within the anterior cruciate ligament (ACL) sub-bundle anatomy was correlated with knee flexion angle changes and provided a measure of differential loading within its sub-bundle microstructure. Introduction. Previous studies have shown that macroscopically the anteromedial (AM) and posterolateral (PL) bundles of the ACL tighten/slacken differently with knee flexion angle. This research used fibre crimp morphology, revealed following in situ fixation of the intact ligament structures, to investigate patterns of differential fibre recruitment across each ACL sub-bundle. Methods. Twelve mature ovine knees were divided into four test-groups of three: control, hyper-extension (8°), neutral position (50°), and deep flexion (170°). For the control group, ligament-bone (tibia) samples were isolated and chemically fixed, unconstrained, in 10% formalin. For the flexed groups the whole joints were first positioned in the relevant angle of flexion using a custom-built rig and formalin-fixed in-situ before undergoing dissection. All ligament-bone samples were decalcified using 10% formic acid and cryo-sectioned in the sagittal plane to obtain 20μm serial slices. These were then examined in their fully hydrated state using differential inference contrast (DIC) microscopy. The degree of crimping, taken as an approximate indicator of elongation and thus loading, was classified as either substantial, intermediate or minimal. Crimp coarseness or wavelength, crimp angle and number of visible apices per unit fibre length were measured and analysed statistically using both ANOVA and post hoc analysis (significance, p < 0.05). Results. Control group. Substantial crimping was present in all regions of both AM and PL bundles. However two distinct crimp morphologies were discerned, coarse and fine. Coarse crimp dominated both the small anterior region of the AM bundle proximal to the tibial plateau and the entire PL bundle. Fine crimp was present in the remaining part of the AM bundle. The wavelengths and maximum angles of the coarse and fine crimp were significantly different at 44.8 ± 5.9 µm/45° and 16.2 ± 3.1 μm/15° respectively. This difference in crimp morphology was consistent along the serial sections of the ACL. From the serial sections, a three dimensional interpretation of the degree of crimping was obtained for the three different loading positions. A summary of the main findings is presented as follows: Hyper-extension. A small antero-medial portion of the AM bundle was substantially crimped (indicating an unloaded state) and the remaining region exhibiting only intermediate crimping; the bulk of the PL bundle was largely free of crimp (indicating a relatively loaded state) except for a substantially crimped region in its postero-lateral aspect. Neutral position. The anterior portion of the AM bundle exhibited minimal crimp but elsewhere was intermediate. The entire PL bundle was substantially crimped. Deep flexion. The substantially crimped medial portion of the AM bundle transformed progressively into an intermediate crimp morphology as the lateral aspect of the bundle was approached. Both the postero-medial and antero-lateral aspects of the PL bundle were largely free of crimp whereas the intervening region was intermediately crimped. Conclusion. Through serial sectioning, this study has revealed differential patterns of fibre recruitment, following loading, in all four quadrants of the sub-bundles of the ovine ACL at different knee flexion angles

Aim. The cut-off values for synovial fluid leukocyte count and neutrophils differential (%PMN) for differentiating aseptic from septic failure in total knee arthroplasties were already defined in the past. Our goal was to determine the cut-off values for synovial fluid leukocyte count and %PMN in failed total hip arthroplasties (THA). Method. Patients undergoing revision THA were prospectively included. In perioperative assessment phase, synovial fluid leukocyte count and %PMN were determined. During the surgery, at least 4 intraoperative samples for microbiological and one for histopathological analysis were obtained. Infection was defined as presence of sinus tract, inflammation in histopathological samples, and ≥2 tissue and/or synovial fluid samples growing the same microorganism. Exclusion criteria were systemic inflammatory diseases, revision surgery performed less than 3 months from index surgery and insufficient tissue sampling. Receiver operating characteristic (ROC) curves were constructed to assess the diagnostic performance and Youden's J statistic was computed to identify optimal cut-off values. Results. During the study period (between June 2006 and June 2011) 227 revision THAs were performed by the senior author. 31 patients were excluded. 196 patients (mean age, 69 years; 68% females) with THA failure were included. Aseptic failure was diagnosed in 150 patients (76,5%) and THA infection was diagnosed in 46 patients (23,5%). Synovial fluid leukocyte counts were significantly higher in the infected group (median, 5.50×10. 6. leukocytes/ml range, 0.05 to 143.9×10. 6. leukocytes/mL) than in the aseptic group (median, 0.23×10. 6. cells/ml; range, 0 to 21.3×10. 6. leukocytes/ml, P<0,0001). The %PMN was also significantly higher in the infected group (median, 83%; range, 6% to 97%) than in the aseptic group (median, 27,5%; range, 0% to 94%, P<0,0001). A synovial fluid leukocyte count of > 1.54×10. 6. leukocytes/ml, had a sensitivity of 63%, specificity of 95%, positive and negative predictive values of 78% and 89%, respectively. A synovial fluid %PMN of > 64%, had a sensitivity of 65%, specificity of 93%, positive and negative predictive values of 73% and 90%, respectively. Conclusion. The synovial fluid leukocyte count of > 1.54×10. 6. leukocytes/ml and %PMN of > 64% are useful and reliable tests for excluding THA infection, having a negative predictive value of around 90%. This tests and calculated cut-off values are highly recommended in the diagnostic process of failed THAs

Introduction. Contemporary total knee systems accommodate for differential sizing between femoral and tibial components to allow surgeons to control soft tissue balancing and optimize rotation. One method some manufacturers use to allow differential sizing involves maintaining coronal articular congruency with a single radius of curvature throughout sizes while clipping the medial-lateral width, called a single coronal geometry system. Registry data show a 20% higher revision rate when the tibial component is smaller than the femur (downsizing) in the DePuy PFC system, a single coronal system, possibly from increased stresses from edge loading or varying articular congruency. We examined a different single coronal geometry knee system, Smith & Nephew Genesis II, to determine if edge loading is present in downsized tibial components by measuring area and location of deviation of the polyethylene articular surface damage. Methods. 45 Genesis II posterior-stabilized polyethylene inserts (12 matched and 33 downsized tibial components) were CT scanned. 3D reconstructions were registered to corresponding pristine component reconstructions, and 3D deviation maps of the retrieved articular surfaces relative to the pristine surfaces were created. Each map was exported as a point cloud to a custom MATLAB code to calculate the area and weighted center of deviation of the articular surfaces. An iterative k-means clustering algorithm was used to isolate regions of deviation, and a shrink-wrap algorithm was applied to calculate their areas. The area of deviation was calculated as the sum of all regions of deviation and was normalized to the area of the articular surface. The location of deviation was described using the weighted center of deviation and the location of maximum deviation on the articular surfaces relative to the center of the post (Fig. 1). Pearson product moment correlations were conducted to examine the correlation between length of implantation (LOI) and the medial and lateral areas of deviation for all specimens, matched components, and downsized components. Results. The mean LOIs for downsized and matched tibial components were not different (36±28 months vs 46±26 months, p=0.24). Areas of deviation for the medial and lateral sides for both downsized and matched components increased with LOI (p<0.001). Medial and lateral sides of matched retrievals were not different in location of maximum deviation, maximum deviation, and weighted center of deviation (p>0.4). The matched and downsized retrievals did not have different centers of deviation in the medial-lateral direction, maximum deviations, or locations of maximum deviations (p>0.1). Discussion. Our results suggest that downsizing the tibial component in the Genesis II system, a single coronal geometry system, did not affect the area or location of deviation on the articular surface. Overall, the weighted center of deviation remained close to the dwell point and did not change as a function of tibial downsizing. However, we saw deviation patterns biased peripherally for inserts with low LOI in both matched and downsized cohorts. With increasing LOI, the deviation expanded to cover the majority of the available articular surface. Our results suggest the need to further examine this and other systems determine the effects of differential sizing. For figures/tables, please contact authors directly.

Introduction: Instrumental Distraction has opened a new window for management of resistant clubfoot. Classical Ilizarov assembly is typically used in patients over the age of two years. We applied the differential distraction technique using the UMEX fixator for ages varying from 6 months to 18 years. This method follows the Ilizarov principle of soft tissue response to tension stress. Materials and Methods: A retrospective review included 120 patients, treated between 1990 – 2001. The majority of the cases were “idiopathic” with 36 feet after failed surgery, 60 feet after failed manipulation and casting, and 11-neglected clubfeet. The non-idiopathic group included 5 feet in patients with arthrogryposis, 5 feet in patients with myelomeningocele, and 3 feet in patients with Streeter’s dysplasia. The UMEX frame spans three segments. The tibial segment consists of two wires trans-fixing the tibia in its proximal third and an axial pin to prevent rocking of the frame. The metatarsal segment incorporates a transfixing pin and two half pins to maintain the transverse arch of the foot. The calcaneal segment includes two transfixing wires and and an axial pin. The three segments are then linked together by a system of clamps, rods and distractors to create the UMEX clubfoot frame. Treatment extends through three stages: Reduction, Retention and Remodeling. The distractors apply differential distraction, and the various deformities are corrected simultaneously. After r eduction is completed the frame is left in a “holding” mode for six more weeks. Thereafter, the assembly is removed and a well-molded below-knee cast is applied for a period of 8 – 12 weeks with monthly cast changes. During the remodeling phase, night splints and walking boots are used for a period of one year. Results: Results were assessed on the basis of the HJD functional rating system. Results were measured at 6-month intervals for 2 years and then yearly. We obtained excellent results in 34.4%; good, in 38.3%; fair, in 16.7% and poor, in 10.8% of the cases. Discussion: The classical Ilizarov method of deformity correction is a constrained assembly applying distraction – compression forces across a predefined hinge. The unconstrined UMEX assembly makes no such demands and correction is achieved at the natural joints. The technique of differential distraction avoids any compression and, as seen in the long-term follow-up, has no ill effects on the growing foot. There is no age limit for use of the system; in older patients, however, incomplete remodeling leaves residual bone deformities. If there is residual foot deformity with completion of the treatment, only limited open surgery is required. In our hands, the use of differential distraction produced functionally serviceable and cosmetically acceptable correction of clubfoot. Conclusion: Our experience demonstrates the effectiveness of differential distraction using the UMEX mini external fixator. This is an excellent technique for correction of complex deformities of the foot and ankle at any age and in the future may replace, to a large degree, the need for open clubfoot surgery

Background: In developing countries, many patients are seen with neglected, residual or recurrent CTEV. Treatment of resistant & neglected CTEV has been a subject of much controversy as the pathoanatomy becomes complex & the true cause of disability becomes difficult to ascertain at times. We treated such patients by controlled, differential, distraction using Joshi’s external stabilisation system (JESS). Aim of study: To explore the role & long term results (minimum follow up 3 years) of controlled, differential, distraction using JESS in relapsed & neglected clubfeet. Methods: 82 patients with 24 bilateral cases (106 feet) treated by JESS at the department of Orthopaedics, KGMU, India from 1992 onwards; followed up for a minimum of 3 years post surgery (average follow up 6.5 years). Patients with non-idiopathic club foot were not included in this study. Outcome evaluation was done by clinical, podographic(footprint), radiological & functional outcomes using Hospital for Joint diseases Orthopaedic Institute functional rating system for clubfoot surgery. Results: Excellent results were obtained in 63%, good in 30% & poor in 7% of the cases. 21% had a partial relapse with only 5% requiring further surgery for deformity correction. 11% of cases needed further surgery in the form of flexor tenotomies, subtalar & mid-foot fusion for persistent pain. Conclusion: Controlled, differential, fractional distraction with JESS is a safe & effective procedure for neglected, resistant & relapsed CTEV. It is effective even in patients after skeletal maturity in correcting the deformity. The procedure is less invasive and the results are good irrespective of the severity of the deformity or age of the patient

To overcome the severely limited regenerative capacity of cartilage, bone marrow mesenchymal stromal cells (MSCs) are an attractive cell source that is accessible less invasively and in higher quantity than articular chondrocytes (ACs). However, current in vitro chondrogenic protocols induce MSCs to form transient cartilage reminiscent of growth plate cartilage that becomes hypertrophic and is remodeled into bone. In contrast, under the same conditions, ACs form stable articular-like cartilage. Developmental studies in mice have revealed that TGF-beta/BMP, Wnt, and Hedghog/PTHrP signaling are the major regulators of both, articular cartilage and endochondral bone formation. While the differential regulation of TGF-beta/BMP and Hedgehog/PTHrP in endochondral MSC versus AC chondral differentiation is established knowledge, little is known about Wnt in these cells. Aim of this study was therefore to compare in vitro levels of Wnt network components in MSC-derived endochondral versus AC-derived articular cartilage. Whole genome expression data comparing human MSCs and ACs at days 0 and 28 of in vitro chondrogenesis were screened for differential expression of Wnt ligands, receptors, co-receptors, activators/inhibitors and signaling molecules. Expression of the most strongly differentially regulated Wnt network genes was studied in detail during in vitro chondrogenesis of MSCs vs ACs via qPCR at days 0, 7, 14, 21, 35, and 42. During early chondrogenesis, most Wnt components were expressed at low levels in both MSCs and ACs, with two exceptions. MSCs started into chondrogenesis with significantly higher levels of the non-canonical ligand WNT5A. ACs on the other hand expressed significantly higher levels of the canonical antagonist FRZB on day 0. During advancing and late chondrogenesis, MSCs downregulated WNT5A but still expressed it at significantly higher levels at day 42 than ACs. Strong regulation was also evident for WNT11 and the receptor PTK7 which were both strongly upregulated in MSCs. Unlike MSCs, ACs barely regulated these non-canonical Wnt genes. With regard to canonical signaling, only the transcription factor LEF1 showed strong upregulation in MSCs, while FZD9 and FRZB were only slightly upregulated in late MSC chondrogenesis. Again, these genes remained unregulated in ACs. Our data suggest that a dynamic Wnt network regulation may be a unique characteristic of endochondral MSC differentiation while during AC chondral differentiation Wnt expression remained rather low and stable. Overall, mRNA of the non-canonical Wnt network components were stronger regulated than canonical factors which may indicate that primarily non-canonical signaling is dynamic in endochondral differentiation. Next step is to assess levels of active and total beta-catenin, the canonical Wnt mediator, and to use Wnt antagonists to establish a causal relationship between Wnt signaling and endochondral differentiation

Introduction. The prevalence of symptomatic osteoarthritis (OA) in the knee is 11–11% compared to 3.4–4.4% in the ankle. In addition to this, 70% of ankle arthritis is post-traumatic while the vast majority of knee arthritis is primary OA. Several reports have previously implicated biochemical differences in extracellular matrix composition between these joint cartilages; however, it is unknown whether there is an inherent difference in their transcriptome and how this might affect their respective functionality under load, inflammatory environment etc. Therefore, we have analysed the transcriptome of ankle and knee cartilage chondrocytes to determine whether this could account for the lower prevalence and altered aetiology of ankle OA. Methods. Human full-depth articular cartilage was taken from the talar domes (n=5) and the femoral condyles (n=5) following surgical amputation. RNA was extracted and next generation sequencing (NGS) performed using the NextSeq®500 system. Statistical analysis was performed to identify differentially regulated genes (p adj < 0.05). Data was analysed using Integrated Pathway Analysis software and genes of interest validated by quantitative PCR. Results. 809 genes were differentially expressed in this NGS study: 781 genes were significantly up-regulated and 27 significantly down-regulated in ankle cartilage with respect to knee. Preliminary analysis has identified several pathways which are differentially regulated including ‘inflammation mediated by cytokines’, ‘glutamate receptor pathway, ‘heterotrimeric-G-protein signalling pathways’, ‘WNT signalling’ and ‘integrin signalling’. Discussion. This is the first report identifying genes that are differentially expressed in ankle cartilage compared to the knee. Validation is currently being performed to ascertain the importance of these gene changes and correlation with their protein expression in the different joints. An understanding of the inherent biological differences in the cartilage between these two joints will provide invaluable insight into why the ankle is relatively spared from primary OA and the majority of ankle arthritis occurs following trauma

Introduction. Positive expectations can increase compliance with treatment and realistic expectations may reduce postoperative dissatisfaction. Recently there are articles regarding expectations of patients from their TKA in western literature and only few articles based on Korean populations which don't encompass the whole spectrum of expectations in Korean patients. In all those articles based on pre-operative expectation, results were applied to whole expectation category uniformly not differentially. We aimed to document the pre-operative expectations in Korean patients undergoing total knee replacement using an established survey form and to determine whether expectations were influenced by socio-demographic factors and socio-demographic factors influences expectation items in particular category uniformly or differentially. Methods. Expectations regarding 19 items in the Knee Replacement Expectation Survey form were investigated in 228 patients scheduled for total knee replacement. The levels and distribution patterns of individual and summated expectation of five expectation categories; relief from pain, baseline activity, high flexion activity, social activity and psychological wellbeing, constructed from the 19 items were assessed. Univariate analyses and Binary logistic regression were performed and analyzed to examine the association of expectations with the socio-demographic factors. Results. The top five expectations among individual items were: improvement in walking ability, relief from pain, ascending and descending stairs, improvement in changing position and improvement in daily activity, respectively. Among the five expectation categories, relief from pain was ranked the highest, followed by restoration of baseline activity, ability to perform high flexion activities, psychological well-being and ability to participate in social activities respectively. Conclusion. There was a high expectation of restoration of walking ability, relief from pain and high flexion activity, whereas the expectation was more variable for psychological well-being and social activities. An age of < 65years, being employed, male gender, previous participation in high level sports activity, less income were all found to be significantly associated with higher expectations in social activity category whereas in baseline category, pain relief category and psychological well being category there are no significantly associated socio-demographic factors found, which shows these are the expectation items/categories which don't depend on socio-demographic factors and are highly expected by all patients undergoing TKA in our study. We also found that Socio-demographic factors influence individual expectation items in particular category differentially not uniformly hence results of individual items don't reflect the whole category or vice versa

Summary Statement. Differential expression of canonical and noncanonical Wnt signalling along cartilage canals and osteochondral junctions is dependent on age. Increased gene expression of PTHrP along cartilage canals and Ihh along osteochondral junctions suggests paracrine feedback in articular-epiphyseal cartilage. Introduction. Wnt signaling has been shown to regulate chondrocyte differentiation during pre-/post-natal cartilage development. In addition, parathyroid-related peptide(PTHrP) and Indian hedgehog(Ihh) create a negative feedback loop in growth cartilage, but less is known in articular cartilage. The objective of this study was to elucidate expression of regulatory molecules in chondrocytes surrounding cartilage canals and osteochondral junctions during neonatal and pre-adolescent development. We hypothesised there would be increased expression of canonical Wnt signalling molecules and Ihh in osteochondral junction chondrocytes compared to cartilage canal chondrocytes. In addition, we hypothesised that Wnt signaling and PTHrP expression would be greater in neonates than pre-adolescents. Patients & Methods. Osteochondral samples were obtained(IACUC-approved) from normal femoropatellar joints of 14 euthanised immature horses(6 neonates, 8 pre-adolescents). Samples were frozen in OCT for laser capture microdissection(LCM) or fixed in 4% paraformaldehyde and paraffin-embedded for immunohistochemistry. Chondrocytes surrounding cartilage canals and osteochondral junctions were captured using LCM. Following RNA isolation, equine-specific β-catenin, Wnt-4, Wnt-5b, Wnt-11, Dickkopf-1(Dkk-1), low-density lipoprotein receptor-related protein-4,-6(Lrp4, Lrp6), Axin1, Wnt inhibitory factor-1(WIF)-1, secreted Frizzled-related protein-1,-3,-5(sFRP), retinoic acid receptor gamma(RARG), RAR-inducible serine carboxypeptidase(SC-PEP), Ihh, PTHrP, VEGF, PDGF, MMP-13, and 18S mRNA expression levels were evaluated by two-step real-time qPCR. Following immunohistochemistry using rabbit polyclonal or mouse monoclonal primary antibodies (confirmed by Western blot), spatial tissue protein expression was scored (0–3). Statistical analysis included Wilcoxon signed rank test(paired samples) or rank sum test(unpaired samples)(P<0.05). Results. Gene expression in chondrocytes along cartilage canals was significantly higher for PTHrP, β-catenin, Lrp6, Axin1, sFRP5, RARgamma, and SC-PEP than osteochondral junctions. Conversely, gene expression of Ihh, Wnt4, Wnt11, sFRP3, and VEGF were higher in osteochondral junction chondrocytes than cartilage canals. There was higher protein expression of β-catenin, PDGF, VEGF, and MMP-13 along osteochondral junctions than cartilage canals of pre-adolescents. Neonates had higher gene expression of PTHrP, Wnt-5b, sFRP3, Lrp6, and RARG in cartilage canal chondrocytes than pre-adolescents, while Ihh, Wnt-11, Lrp4, and Dkk1 were significantly higher in pre-adolescents. Immunostaining was higher for β-catenin and Wnt-11 in pre-adolescent osteochondral junction cartilage than neonates. No differences were found between age groups for Wnt-4 immunostaining. Dkk1 protein expression was significantly higher in the middle cartilage layer of pre-adolescents than neonates. Immunostaining was greater for Ihh and PTHrP in the deep cartilage layer of pre-adolescents than neonates. PDGF, VEGF, and MMP13 protein expression was higher in the superficial cartilage layer of pre-adolescents than neonates. Discussion. Wnt/β-catenin and Ihh/PTHrP signaling regulate cartilage differentiation during development and are important in endochondral ossification. This study revealed cell-specific, age-related differences in gene/protein expression of both regulatory pathways. Cells surrounding cartilage canals typically appeared small/rounded compared to larger chondrocytes along osteochondral junctions, likely due to different developmental stages. Higher PTHrP gene expression along cartilage canals and Ihh expression along osteochondral junctions may reflect these stages, suggesting paracrine feedback in articular-epiphyseal cartilage. β-catenin signaling may induce chondrocyte hypertrophy, potentially by enhancing Ihh and MMP-13 expression. Differential expression of canonical(β-catenin, Wnt-4, Lrp4, Lrp6) and noncanonical Wnt signalling(Wnt-5b, Wnt-11) and Wnt inhibitors (Dkk1, Axin1, sFRP3, sFRP5, Wif-1) surrounding cartilage canals and osteochondral junctions provides evidence of age-related interactions during postnatal development