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

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

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

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. 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

Identification of modalities and procedures to improve the differential diagnosis of septic and aseptic cases in patients with joint-related pain after total hip or knee alloplasty (THA/TKA). A prospective cohort of 147 patients presenting with problems related to previous THA or TKA was included and subjected to a comprehensive diagnostic algorithm. The standard diagnostics were supplemented with novel or improved methods for sampling of clinical specimens, sonication of retrieved implant parts, prolonged and effective culture of microorganisms, and dedicated clinical samples for molecular biological detection and identification of microorganisms. Furthermore, comprehensive pain investigations and nuclear imaging were employed. For each case the clinical management was decided upon in a clinical conference with participation of clinical microbiologist, orthopedics and experts in nuclear imaging. The clinical management of patients was blinded against the molecular biological detection of microorganisms. Patients grouped as follows: 69 aseptic, 19 acute septic, 19 chronic septic, 40 pain/unresolved. Sonication of retrieved implant parts resulted in detection of biofilm not detected by standard specimens, i.e. joint fluid and periprosthetic tissue biopsies. Next generation sequencing detected and identified few infections not detected by culture. Molecular analyses showed more polymicrobial infections than culture. Nuclear imaging was inconclusive with respect to recommendation of changed setup. Analysis of blood based biomarkers is ongoing. Patients with chronic pain are undergoing follow-up. The special emphasis put on detection of infections resulted in detection of infections in joints that otherwise would have been categorized as aseptic loosening. Clinical management for these cases was changed accordingly. The cross-disciplinary clinical conference is considered valuable for clinical management. The clinical relevance of the polymicrobial nature of infections as diagnosed employing next generation sequencing is yet to be established. Long-term follow-up is planned

Aims

The aims of this study were to describe the demographic, socioeconomic, and educational factors associated with core surgical trainees (CSTs) who apply to and receive offers for higher surgical training (ST3) posts in Trauma & Orthopaedics (T&O).

Hip and knee arthroplasty (HKA) are two of the most successful orthopaedic procedures. However, one major complication necessitating revision surgery is osteolysis causing aseptic loosening of the prosthesis. JAK-STAT has been demonstrated to influence bone metabolism and can be regulated by microRNA (miRNA). Adult patients with osteolysis or aseptic loosening undergoing revision HKA were recruited. Age and gender matched patients undergoing primary hip or knee arthroplasty were our controls. Samples of bone, tissue and blood were collected and RNA isolation was performed. The best quality samples were used for RNA-sequencing. Data analysis was performed using RStudio and Galaxy to identify differentially expressed genes. Western blotting of IL6 was used to confirm protein expression. Five circulating miRNA were identified which had 10 differentially expressed genes in bone and 11 differentially expressed genes in tissue related to the JAK-STAT pathway. IL6 in bone and EpoR in bone were highly significant and IL6 in tissue, MPL in bone, SOCS3 in tissue, JAK3 in bone and SPRED1 in bone were borderline significant. Western blot results demonstrated up-expression of IL6 in bone tissue of revision patients. Periprosthetic osteolysis and aseptic loosening can be attributed to miRNA regulation of the JAK-STAT pathway in osteoblasts and osteoclasts, leading to increased bone resorption. These findings can be used for further experiments to determine utility in the clinical setting for identifying diagnostic markers or therapeutic targets

Non-invasive sampling of tumor-derived genetic material in circulation through liquid biopsy may be very beneficial for an accurate diagnosis and evaluation of response to treatment in patients with malignant and benign soft tissue tumors. We previously showed that tumor-derived genomic aberrations can be detected in plasma of patients with leiomyosarcoma (LMS) and leiomyoma (LM). In LMS patients, we also showed that the levels of circulating tumor DNA (ctDNA) correspond with response to treatment. We developed an approach tailored to genomic profile of LMS (characterized by intermediate levels of point mutations and copy number alterations, CNAs). Based on TCGA data, we designed a panel of 89 most frequently mutated genes in LMS, which we profiled in plasma DNA by deep sequencing. In parallel, plasma samples were analyzed by shallow whole genome sequencing for detection of CNAs. With this approach, we detected ctDNA in 71% (20/28) of samples from 6/7 patients with advanced disease with >98% specificity. The combination approach for orthogonal profiling of point mutations and CNAs proved to increase the sensitivity of ctDNA detection. Currently, we seek to further improve the sensitivity of ctDNA detection by refining our capture panel and tracking LMS-specific DNA methylation markers in circulation, in addition to point mutations and CNAs. The ultimate goals of our ctDNA studies are 1) to develop a highly sensitive assay for evaluation of response to therapy and long-term surveillance for patients with LMS, and 2) to develop a blood-based test for accurate pre-operative distinction between LMS and LM. To identify LMS-specific DNA methylation markers, we analyzed a test cohort of 76 LM, 35 uterine LMS and 31 extra-uterine LMS by Illumina Infinium EPIC arrays. We identified differentially methylated CpGs between LM and uterine LMS, and between LM and all LMS using a newly developed custom pipeline in R. The results of this analysis are currently being validated in a new dataset of 41 LM and 153 LMS generated by our group. Recently published (PMID: 34301934) genomic data from new 53 LMS samples are used to refine the panel of the most frequently mutated genes that we identified previously in the LMS TCGA data. Our preliminary analysis of test cohort revealed >270 differentially methylated CpGs between LM and uterine LMS, and >1000 differentially methylated CpGs between LM and all LMS. The preliminary analysis of genomic data shows that the initial panel of 89 frequently mutated genes could be substantially narrowed down to cover only selected tumor suppressor genes. Once validated, these results will be used to refine the ctDNA assay for LMS and LM. Our results point to multiple epigenetic markers that could be used for ctDNA profiling, in addition to point mutations or CNAs. Further validation will allow us to select the most reliable LMS- and LM-specific DNA methylation markers and the most frequently mutated regions across independent datasets, and these markers will be incorporated into our new ctDNA test for a concurrent detection of point mutations, CNAs and DNA methylation markers in circulation

Aim. Evaluate the metabolites composition of the synovial fluid from patients with PJI or aseptic failure of total knee arthroplasties. Method. The synovial fluids from 21 patients scheduled for revision total knee arthroplasty (11 with the diagnosis of PJI and 10 with aseptic failures) were analyzed using 1D 1H NMR spectroscopy. Univariate and multivariate statistical analyses were used to identify metabolites that were differentially abundant between those groups. Results. A total of 28 metabolites were identified and five of them found to be differentially abundant between infected and non-infected synovial fluids. Lactate, acetate and 3-hydroxybutyrate were found to be in a higher concentration, and glucose and creatine were found reduced in the synovial fluid from PJI patients. Conclusions. Synovial fluid from patients with PJI exhibit a distinct metabolic profile, possibly reflecting metabolic adaptation that occurs in the infected periprosthetic microenvironment. Further research and studies are warranted to gain a broader insight into the metabolic pathways engaged by both pathogen and immune cells in the context of a PJI

Aims. This study explored the shared genetic traits and molecular interactions between postmenopausal osteoporosis (POMP) and sarcopenia, both of which substantially degrade elderly health and quality of life. We hypothesized that these motor system diseases overlap in pathophysiology and regulatory mechanisms. Methods. We analyzed microarray data from the Gene Expression Omnibus (GEO) database using weighted gene co-expression network analysis (WGCNA), machine learning, and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis to identify common genetic factors between POMP and sarcopenia. Further validation was done via differential gene expression in a new cohort. Single-cell analysis identified high expression cell subsets, with mononuclear macrophages in osteoporosis and muscle stem cells in sarcopenia, among others. A competitive endogenous RNA network suggested regulatory elements for these genes. Results. Signal transducer and activator of transcription 3 (STAT3) was notably expressed in both conditions. Single-cell analysis pinpointed specific cells with high STAT3 expression, and microRNA (miRNA)-125a-5p emerged as a potential regulator. Experiments confirmed the crucial role of STAT3 in osteoclast differentiation and muscle proliferation. Conclusion. STAT3 has emerged as a key gene in both POMP and sarcopenia. This insight positions STAT3 as a potential common therapeutic target, possibly improving management strategies for these age-related diseases. Cite this article: Bone Joint Res 2024;13(8):411–426

Aim. Prosthetic joint infection (PJI) presents the second most common complication of total joint arthroplasty (TJA). Accumulating evidence suggests that up to 20% of aseptic failures are low-grade PJI. However, there is still no single test to reliably diagnose all PJI. In his thesis, Mazzucco emphasized the viscosity differences between normal, osteoarthritic, and rheumatic synovial fluid. Similarly, a recent study by Fu et al. reported significantly lower viscosity in patients with PJI compared to the aseptic failure cohort. The primary aim of our study was to determine whether synovial fluid viscosity is a more reliable diagnostic criterion for PJI compared to the synovial fluid cell count with differential and serum C-reactive protein (CRP) levels. Method. We prospectively analyzed the viscosity of synovial fluid samples obtained during TJA of hip and knee joint revision procedures. We sampled 2.5–5 mL of synovial fluid for viscosity measurement. The samples were centrifuged (4 min at 7000 rpm) and the resulting supernatant was immediately transferred into the Ostwald viscometer. Viscosity was derived from the time required for a given volume of synovial fluid to pass the viscometer at 20 °C. The synovial fluid samples were also analysed for their cell count with differential and serum CRP was measured. The definite diagnosis of PJI was established on basis of EBJIS criteria. For the viscosity, the threshold for detecting PJI was set at 65 seconds. Results. Between December 2020 and March 2021, we analyzed 12 knee and 11 hip TJA revision samples. These included 14 septic and 9 aseptic synovial fluid samples. The average viscometer time in the PJI group was 31s (range 20–48s) compared to 247s (range 68–616s) in the group of aseptic revision procedures. The specificity and sensitivity of our viscosity measurements were 100%. The sensitivity and specificity of cell count was 100% and 85.7%, for the synovial fluid differential they were 100% and 85.7%, and for the CRP they were 88.9% and 71.4%, respectively. Conclusions. Our study is the first to report a significant difference in synovial fluid viscosity between the PJI and the aseptic cohort. It points towards the diagnostic superiority of viscosity measurements over conventional synovial fluid cell count, synovial fluid differential, and serum CRP levels. Albeit currently limited by small sample size, the study remains ongoing

Aim. Our goal is to assess diagnostic accuracy of synovial fluid testing in diagnosing prosthetic joint infection (PJI) as defined by the European Bone and Joint Infection Society (EBJIS). In addition to differential leukocyte count, simples and inexpensive biomarkers such as synovial fluid C-reactive protein (CRP), adenosine deaminase (ADA) and alpha-2-macrogloblulin(A2M) were also investigated and its possible role in increasing accuracy assessed. Method. Between January/2013 and December/2019 total hip or knee arthroplasty revision cases (regardless of preoperative diagnosis) were prospectively included provided enough synovial fluid for biomarker analysis was collected and at least four tissue samples, as well as the implant for sonication, were gathered for microbiological study. Definitive diagnosis was classified according to the new EBJIS PJI definition. Using receiver operating characteristic curves, we determined cutoff values as well as diagnostic accuracy for each marker. Results. Out of 364 revision arthroplasties performed, 102 fully respected inclusion criteria. There were 58 unlikely, 8 likely and 36 confirmed infections. Synovial fluid total leukocyte count, proportion of polymorphonuclear neutrophils (PMN), CRP, ADA and A2M were significantly different between groups. Area under the curve was 0.94 for total leucocyte count, 0.91 for proportion of PMN, 0.90 for CRP, 0.82 for ADA and 0.76 for A2M. Sensitivity, specificity, and predictive values for statistically optimal but also selected rule-in and rule-out cutoffs values are shown in Table 1. Interpreting a raised level of CRP(>2.7mg/L) or ADA(>60U/L) together with high leukocyte count (>1470 cells/μL) or proportion of PMN (>62.5%) significantly increases specificity and positive predictive value for affirming PJI. Conclusions. Differential leukocyte count cutoffs proposed by the EBJIS PJI definition are shown to perform well in ruling out (<1,500 cells/μL) and ruling in (>3,000 cells/μL) PJI. Adding simple and inexpensive biomarkers such synovial CRP or ADA is helpful in interpreting inconclusive results. For any tables or figures, please contact the authors directly

Tendinopathy is a tendon pathology often resulting from a failed healing response to tendon injury. Activated protein C (APC) is a natural anti-coagulant with anti-inflammatory and wound healing promoting functions, which are mainly mediated by its receptors, endothelial protein C receptor (EPCR) and protease activated receptors (PARs). This study aimed to determine whether APC stimulates tenocyte healing and if so, to assess the involvement of the receptors. Mouse-tail tenocytes were isolated from 3-week-old wild type (WT), PAR- 1 knockout (KO) and PAR-2 KO mice. The expression of EPCR, PAR-1 and −2 and the effect of APC on tenocytes tendon healing and the underlying mechanisms were investigated by Reverse transcription real time PCR, western blot, 3- (4,5-dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide (MTT) assay, zymography, and scratch wound healing/ migration assay. When compared to WT cells, PAR-1 KO tenocytes showed increased cell proliferation (3.3-fold, p<0.0001), migration (2.7-fold, p<0.0001) and wound healing (3-fold, p<0.0001), whereas PAR-2 KO cells displayed decreased cell proliferation (0.6-fold, p<0.05) and no change in cell migration or wound healing. APC at 1 μg/ml stimulated WT and PAR-1 KO tenocyte proliferation (~1.3, respectively, p<0.05) and wound healing (~1.3-fold, respectively, p<0.05), and additionally promoted PAR1-KO cell migration (1.4-fold, p<0.0001). APC only increased the migration (2-fold, p<0.05) of PAR-2 KO tenocytes. The activation of AKT, extracellular signal-regulated kinase (ERK)-2, and glycogen synthase kinase (GSK)-β3, the intracellular molecules that are associated with cell survival/growth, and matrix metalloproteinase (MMP)-2 that is related to cell migration and wound healing, were increased in all three cell lines in response to APC treatment. These findings show that PAR-1 and PAR-2 act differentially in tenocyte proliferation/migration/wound healing. APC likely promotes tenocyte proliferation/ wound healing via PAR-2, not PAR-1

Aim. Treatment algorithms for fracture-related nonunion depend on the presence or absence of bacterial infection. However, the manifestation of septic nonunion varies. Low-grade infections, unlike manifest infections, lack clinical signs of infection and present similarly to aseptic nonunion. The clinical importance of low-grade infection in nonunion is not entirely clear. Therefore, the aim of this study was to evaluate the clinical relevance of low-grade infection in the development and management of femoral or tibial nonunion. Method. A prospective, multicenter clinical study enrolled patients with nonunion and regular healed fractures. Preoperatively, complete blood count without differential, C-reactive protein (CRP), and procalcitonin were obtained, clinical signs of infection were recorded, and a suspected septic or aseptic diagnosis was made based on history and clinical examination. During surgical nonunion revision or routine implant removal, tissue samples were collected for microbiology and histopathology, and osteosynthesis material for sonication. Nonunion patients were followed for 12 months. Definitive diagnosis of “septic” or “aseptic” nonunion was made according to diagnostic criteria for fracture-related infection, considering the results of any further revision surgery during follow-up. Results. 34 patients with regular healed fractures were included. 62 nonunion patients were diagnosed as aseptic, 22 with manifest, and 23 with low-grade infection. The positive predictive value was 88% and the negative predictive value 72% for the suspected diagnosis. The nonunion groups had significantly higher CRP levels than the regular healer group. Differentiation between septic and aseptic nonunion based on blood values was not possible. Low-grade infection demonstrated less frequently histopathologic signs of infection than manifest infection (22% vs. 50%, p=0.048), with 15% of regular healers having histopathologic signs of infection. Cutibacterium acnes was less present in manifest compared to low-grade infection (p=0.042). Healing rates for septic nonunion involving C. acnes were significantly lower for manifest infection (20%) than for low-grade infection (100%, p=0.002). Patients with low-grade infection were treated with systemic antibiotics less frequently than patients with manifest infection (p=0.026), with no significant difference in healing rate (83% vs. 64%), which was slightly lower for low-grade infection than for aseptic nonunion (90%). Conclusions. Low-grade infections play a significant role in nonunion development and are difficult to diagnose preoperatively due to the lack of clinical signs of infection and unremarkable blood counts. However, our results imply that for low-grade infections, antibiotic therapy may not always be mandatory to heal the nonunion. This study was supported by the German Social Accident Insurance (FF-FR0276)

Aim. Prosthetic joint infection (PJI) represents the second most frequent complication of total joint arthroplasty (TJA) with up to 20% of low-grade PJI treated as aseptic failure. Sensitive diagnostic criteria have been provided by EBJIS. However, to date there is no single test to reliably diagnose all PJIs. Studies of Mazzucco et al. and Fu et al. suggest that synovial fluid (SF) viscosity could be considered as an important marker for PJI. The primary aim of our study was to determine if SF viscosity is a more reliable diagnostic criterion of PJI than the SF cell count with differential (CCD), and the combined diagnostic value of SF viscosity and CCD. Method. We prospectively analysed the viscosity of SF samples obtained during TJA of hip and knee revisions. We sampled 2.5–5mL of SF for viscosity and CCD. Intraoperatively, 1mL of the sample was analysed for the CCD. The remaining SF was centrifuged for 4min at 7000rpm. The viscosity of the supernatant was determined on Ostwald viscometer as the time required to pass the viscometer at 20°C. During each surgery at least 5 microbiological and multiple histopathological samples were harvested, and explant sonication was performed. The diagnosis was based on EBJIS definition. The viscosity threshold for detecting PJI was set at 65 seconds. Results. Between December 2020 and January 2023, we analysed 65 knee and 47 hip TJA revision procedures. There were 55 septic and 57 aseptic diagnoses. As a diagnostic marker of PJI, SF viscosity achieved 100% sensitivity and 82.5% specificity, with area under the receiver operating characteristic curve (AUC) of 0.832 (95% CI 0.739, 0.925). The specificity and sensitivity of SF CCD were 98.2% and 78.2%, respectively, with AUC of 0.921 (95% CI 0.869, 0.974). Of the 10 cases incorrectly diagnosed as aseptic based on SF viscosity, 2 were acute traumas and 8 metalloses. The SF CCD in all these cases was <0.5. Of the 12 cases incorrectly diagnosed as aseptic based on SF CCD, 6 cases were culture negative, 4 C. acnes and 2 S. epidemidis isolates in microbiology. Taken together, SF viscosity and CCD achieved a combined AUC of 0.953 (95% CI 0.919, 0.987). Conclusions. Our study is the first to report that SF viscosity is more sensitive but slightly less specific for PJI than SF CCD. The study demonstrates diagnostic value of combining SF viscosity with CCD in decision making in TJA revision surgery

Hallux valgus surgery can result in moderate to severe post-operative pain requiring the use of narcotic medication. The percutaneous distal metatarsal osteotomy is a minimally invasive approach which offers many advantages including minimal scarring, immediate weight bearing and decreased post-operative pain. The goal of this study is to determine whether the use of narcotics can be eliminated using an approach combining multimodal analgesia, ankle block anesthesia and a minimally invasive surgical approach. Following ethics board approval, a total of 160 ambulatory patients between the ages of 18-70 with BMI ≤ 40 undergoing percutaneous hallux valgus surgery are to be recruited and randomized into Narcotic-free (NF) or Standard (S) groups. To date, 72 patients have been recruited (38 NF and 34 S). The NF group received acetaminophen, naproxen, pregabalin 75mg and 100mg Ralivia (tramadol extended release) before surgery and acetaminophen, naproxen, pregabalin 150mg one dose and Ralivia 100mg BID for five days, as well as a rescue narcotic (hydromorphone, 1mg pills) after surgery. The S group received acetaminophen and naproxen prior to surgery and acetaminophen, naproxen and hydromorphone (1mg pills) post-operatively, our current standard. Visual analog scales (VAS) were used to assess pain and narcotic consumption was recorded at 6, 12, 24, 36, 48, 72 hours and seven days post-operatively. Patients wore a smart watch to record the number of daily steps and sleep hours. A two-sided t-test was used to compare the VAS scores and narcotic consumption. During the first post-operative week, the NF group consumed in total an average of 6.5 pills while the S group consumed in total an average of 16 pills and this difference was statistically significant (p-value=0.001). Importantly, 19 patients (50%) in the NF group and four patients (12%) in the S group did not consume any narcotics post-operatively. For the VAS scores at 24, 48, 72 hours and seven days the NF group's average scores were 2.17, 3.17, 2.92, 2.06 respectively and the S group's average scores were 3.97, 4.2, 3.23, 1.97. There was a statistically significant difference between the groups at 24 and 48hours (the NF group scored lower on the VAS) with a p-value of 0.0008 and 0.04 respectively, but this difference is not considered clinically significant as the minimal clinically important difference reported in the literature is a two-point differential. The NF group walked an average of 1985.75 steps/day and slept an average of 8h01 minute/night, while the S group walked an average of 1898.26 steps/day and slept an average of 8h26 minutes/night in the first post-operative week. Hallux valgus remains a common orthopedic foot problem for which surgical treatment results in moderate to severe post-operative pain. This study demonstrates that with the use of multimodal analgesia, ultrasound guided ankle blocks and a percutaneous surgical technique, narcotic requirements decreased post-operatively. The use of long-acting tramadol further decreased the need for narcotic consumption. Despite decreased use of narcotics, this combined novel approach to hallux valgus surgery allows for early mobilization and excellent pain control