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Background Patella resurfacing in total knee arthroplasty is a contentious issue. The literature suggests that resurfacing of the patella is based on surgeon preference, and little is known about the role and timing of resurfacing and how this affects outcomes. Methods We analyzed 134,799 total knee arthroplasties using data from the Australian Orthopaedic Association National Joint Replacement Registry. Hazards ratios (HRs) were used to compare rates of early revision between patella resurfacing at the primary procedure (the resurfacing group, R) and primary arthroplasty without resurfacing (no-resurfacing group, NR). We also analyzed the outcomes of NR that were revised for isolated patella addition. Results At 5 years, the R group showed a lower revision rate than the NR group: cumulative per cent revision (CPR) 3.1% and 4.0%, respectively (HR = 0.75, p < 0.001). Revisions for patellofemoral pain were more common in the NR group (17%) than in the R group (1%), and 'patella only' revisions were more common in the NR group (29%) than in the R group (6%). Non-resurfaced knees revised for isolated patella addition had a higher revision rate than patella resurfacing at the primary procedure, with a 4-year CPR of 15% and 2.8%, respectively (HR = 4.1, p < 0.001). Interpretation Rates of early revision of primary total knees were higher when the patella was not resurfaced, and suggest that surgeons may be inclined to resurface later if there is patellofemoral pain. However, 15% of non-resurfaced knees revised for patella addition are re-revised by 4 years. Our results suggest an early beneficial outcome for patella resurfacing at primary arthroplasty based on revision rates up to 5 years. [ABSTRACT FROM AUTHOR]

With the aim of providing information for modelling joint and limb systems, widely available constitutive hyperelastic laws are evaluated in this paper for their ability to predict the mechanical responses of normal and osteoarthritic articular cartilage. Load-displacement data from mechanical indentation were obtained for normal and osteoarthritic cartilage at 0.1 s(-1) and 0.025 s(-1) and converted to the stress-stretch ratio. The data were then fitted to the Arruda-Boyce, Mooney-Rivlin, neo-Hookean, Ogden, polynomial, and Yeoh hyperelastic laws in the MATLAB environment. Although each of the hyperelastic laws performed satisfactorily at the higher rate of loading, their ability to fit experimental data at the lower loading rate varied considerably. For the preferred models, coefficients were provided for stiff, soft, and average tissues to represent normal and degraded tissue at high and low loading rates. The present authors recommend the use of the Mooney-Rivlin or the Yeoh models for describing both normal and degraded articular cartilage, with the Mooney-Rivlin model providing the best compromise between accuracy and required computational power. [ABSTRACT FROM AUTHOR]

A randomized controlled trial was performed to assess the effect of a rim cutter device on cement mantles in modern elective total hip arthroplasty using a flanged acetabular component. Forty patients were randomized to a rim cutter (21) or control (19) group. A statistically significant improvement in cement penetration was demonstrated in zone 1 (10.1 vs 8.6 mm, P = .023), and in cement mantle thickness in zones 2 and 3 (7.8 and 6.7 mm vs 5.7 and 5.4 mm [P < .001 and P = .017]), with a reduced incidence of bottoming out of the socket (1/21 vs 8/19 [P = .007]). Cement mantle thicknesses greater than 8 mm were achieved more consistently in the rim cutter group (30% vs 2%). This technique improves cement penetration and mantle thickness in a reliable manner. [ABSTRACT FROM AUTHOR]

This paper is a sequel to previously published findings showing that mechanical indentation alone cannot clearly discriminate between normal and degraded articular cartilage. Consequently, the structural elasticity potential Rc = epsilon r/sigma i, which combines indentation stress sigma i with near-instantaneous rebound epsilon r following unloading, is hypothesized as a potential cartilage assessment parameter, which arguably measures the integrity of the collagen fibre-proteoglycan entrapment system. To establish the validity of our hypothesis, samples of normal intact, artificially degraded, and osteoarthritic bovine cartilage were subjected to quasi-static compression at 0.1 s(-1) and 0.025 s(-1) to 30 per cent strain and then unloaded. A significant reduction in recovery was observed for artificially and naturally degraded samples in the first 5s following unloading (p < 0.01). The structural elasticity potential provided a considerable improvement over the results obtained using the individual indentation and rebound parameters to distinguish between paired normal and artificially degraded samples and indicated a high statistical significance of p < 0.005 when applied to the differentiation of normal and osteoarthritic samples. [ABSTRACT FROM AUTHOR]

BACKGROUND: Metal particles are generated during bone preparation in knee arthroplasty. These particles may produce third-body wear, or may have a role in osteolysis. Knowledge of their characteristics may help in the development of methods to reduce the amount of metal debris during bone cutting procedures. MATERIAL AND METHODS: We performed bony resection of the distal femur and proximal tibia on 15 pig knees, simulating a total knee arthroplasty (TKA). Metal debris was collected from the saw blades, cutting blocks and bone surfaces and cleaned for microanalysis. RESULTS: The average loss of metal from the saw blades was 1.13 mg. The average volume of a wear particle was 3.4 x 10(-16) m(3). From this, it was estimated that approximately 500,000 particles are released from the saw blade alone. Material analysis of the particles indicated that the majority originated from the metallic cutting guides, suggesting that many millions of wear particles would be generated during the surgical procedure. Two particle shapes predominated: platelet shape and ploughed shape. INTERPRETATION: Wear particles are produced during resection for a TKA. These may enter the artificial articulation and cause accelerated wear and macrophage activation. Redesign of cutting blocks and saw blades may reduce the amount of debris produced during surgery. [ABSTRACT FROM AUTHOR]

We report two Australian patients with possible cobalt toxicity related to metal-on-metal total hip replacements. Both patients were treated for osteoarthritis with a DePuy ASR (articular surface replacement) XL Acetabular Hip System prosthesis, which contains cobalt and chromium, and which has recently been recalled from the market. [ABSTRACT FROM AUTHOR]

The treatment of critical-size bone defects with irregular shapes remains a major challenge in the field of orthopedics. Bone implants with adaptability to complex morphological bone defects, bone-adhesive properties, and potent osteogenic capacity are necessary. Here, a shape-adaptive, highly bone-adhesive, and ultrasound-powered injectable nanocomposite hydrogel is developed via dynamic covalent crosslinking of amine-modified piezoelectric nanoparticles and biopolymer hydrogel networks for electrically accelerated bone healing. Depending on the inorganic-organic interaction between the amino-modified piezoelectric nanoparticles and the bio-adhesive hydrogel network, the bone adhesive strength of the prepared hydrogel exhibited an approximately 3-fold increase. In response to ultrasound radiation, the nanocomposite hydrogel could generate a controllable electrical output (-41.16 to 61.82 mV) to enhance the osteogenic effect in vitro and in vivo significantly. Rat critical-size calvarial defect repair validates accelerated bone healing. In addition, bioinformatics analysis reveals that the ultrasound-responsive nanocomposite hydrogel enhanced the osteogenic differentiation of bone mesenchymal stem cells by increasing calcium ion influx and up-regulating the PI3K/AKT and MEK/ERK signaling pathways. Overall, the present work reveals a novel wireless ultrasound-powered bone-adhesive nanocomposite hydrogel that broadens the therapeutic horizons for irregular bone defects., (© 2024. The Author(s).)

This study examines the potential cost savings for the health system and the community in a broadly accessible model through the increased utilization of unicompartmental knee arthroplasty (UKA) using robotic arm-assisted UKA (raUKA) versus conventional total knee arthroplasty (cTKA). We retrospectively reviewed 240 patients where the first 120 consecutive raUKA performed during this period were matched to 120 cTKAs. Clinical data from the medical records and costs for procedure for each component were collected. Bivariate analyses were performed on the data to determine if there were statistically significant differences by surgery type in clinical outcomes and financial costs. There was a significantly lower cost incurred for raUKA versus cTKA with an average saving of AU$7,179 per case. The operating time (86.0 vs. 75.9 minutes; p  = 0.004) was significantly higher for raUKA, but the length of stay was significantly lower (1.8 vs. 4.8 days; p  < 0.001). There was a significant difference in the use of opioids between raUKA and cTKA (125.0 morphine equivalent [ME] vs. 522.1 ME, p  < 0.001). This study demonstrated that the use of raUKA rather than cTKA in suitably indicated patients may realize significant cost savings., Competing Interests: None declared., (Thieme. All rights reserved.)

Chondrogenic induction of bone-marrow-derived stromal cells (BMSCs) is typically accomplished with medium supplemented with growth factors (GF) from the transforming growth factor-beta (TGF-β)/bone morphogenetic factor (BMP) superfamily. In a previous study, we demonstrated that brief (1-3 days) stimulation with TGF-β1 was sufficient to drive chondrogenesis and hypertrophy using small-diameter microtissues generated from 5000 BMSC each. This biology is obfuscated in typical large-diameter pellet cultures, which suffer radial heterogeneity. Here, we investigated if brief stimulation (2 days) of BMSC microtissues with BMP-2 (100 ng/mL) or growth/differentiation factor (GDF-5, 100 ng/mL) was also sufficient to induce chondrogenic differentiation, in a manner comparable to TGF-β1 (10 ng/mL). Like TGF-β1, BMP-2 and GDF-5 are reported to stimulate chondrogenic differentiation of BMSCs, but the effects of transient or brief use in culture have not been explored. Hypertrophy is an unwanted outcome in BMSC chondrogenic differentiation that renders engineered tissues unsuitable for use in clinical cartilage repair. Using three BMSC donors, we observed that all GFs facilitated chondrogenesis, although the efficiency and the necessary duration of stimulation differed. Microtissues treated with 2 days or 14 days of TGF-β1 were both superior at producing extracellular matrix and expression of chondrogenic gene markers compared to BMP-2 and GDF-5 with the same exposure times. Hypertrophic markers increased proportionally with chondrogenic differentiation, suggesting that these processes are intertwined for all three GFs. The rapid action, or "temporal potency", of these GFs to induce BMSC chondrogenesis was found to be as follows: TGF-β1 > BMP-2 > GDF-5. Whether briefly or continuously supplied in culture, TGF-β1 was the most potent GF for inducing chondrogenesis in BMSCs.

If it were possible to purchase tumour-spheroids as a standardised product, ready for direct use in assays, this may contribute to greater research reproducibility, potentially reducing costs and accelerating outcomes. Herein, we describe a workflow where uniformly sized cancer tumour-spheroids are mass-produced using microwell culture, cryopreserved with high viability, and then cultured in neutral buoyancy media for drug testing. C4-2B prostate cancer or MCF-7 breast cancer cells amalgamated into uniform tumour-spheroids after 48 h of culture. Tumour-spheroids formed from 100 cells each tolerated the cryopreservation process marginally better than tumour-spheroids formed from 200 or 400 cells. Post-thaw, tumour-spheroid metabolic activity was significantly reduced, suggesting mitochondrial damage. Metabolic function was rescued by thawing the tumour-spheroids into medium supplemented with 10 µM N -Acetyl-l-cysteine (NAC). Following thaw, the neutral buoyancy media, Happy Cell ASM, was used to maintain tumour-spheroids as discrete tissues during drug testing. Fresh and cryopreserved C4-2B or MCF-7 tumour-spheroids responded similarly to titrations of Docetaxel. This protocol will contribute to a future where tumour-spheroids may be available for purchase as reliable and reproducible products, allowing laboratories to efficiently replicate and build on published research, in many cases, making tumour-spheroids simply another cell culture reagent.

Background: Pelvic skeletal asymmetry can result in rotational differences and morphologic bony prominence variance between the left and right hemipelvis. When selecting bony reference points for modern computed tomography-based robotic total hip arthroplasty planning, it is unclear which bony landmarks are the most reliable and accurate, especially in the presence of significant pelvic asymmetry., Methods: A retrospective study was conducted utilizing a database of computed tomography scans. Multiple bony landmarks in the pelvis and femur were selected for comparison, with the aim of measuring pelvic asymmetry. Specifically, the study measured the average difference in lateral offset between the left and right hemipelvis caused by pelvic asymmetry. Landmarks were also compared to determine the impact of pelvic asymmetry on hip length, femur length, and limb length discrepancies. Furthermore, a scenario was simulated in the software whereby a total hip replacement was inserted, potentially changing the hip length. The impact of pelvic reference point selection on the measurement of this simulated change in hip length was examined., Results: This study population showed widespread pelvic asymmetry. The anatomical landmarks of the opposite side cannot be relied upon for predicting the anatomy of the affected side. The center of rotation axis is more reliable than the inferior obturator foramen axis for hip length discrepancy due to pelvic asymmetry ( P < .05)., Conclusions: Current computer-assisted surgery THR software reports measurements of global offset and hip length that do not consider pelvic asymmetry. Surgeons are not given confidence ranges to represent the potential impact of asymmetry on the global offset and hip length values. Surgeons following these numbers to guide implant position may incur implant placement error should significant pelvic asymmetry be present in a given patient., (© 2023 The Authors.)

The financial viability of a cell and tissue-engineered therapy may depend on the compatibility of the therapy with mass production and cryopreservation. Herein, we developed a method for the mass production and cryopreservation of 3D cartilage microtissues. Cartilage microtissues were assembled from either 5000 human bone marrow-derived stromal cells (BMSC) or 5000 human articular chondrocytes (ACh) each using a customized microwell platform (the Microwell-mesh). Microtissues rapidly accumulate homogenous cartilage-like extracellular matrix (ECM), making them potentially useful building blocks for cartilage defect repair. Cartilage microtissues were cultured for 5 or 10 days and then cryopreserved in 90% serum plus 10% dimethylsulfoxide (DMSO) or commercial serum-free cryopreservation media. Cell viability was maximized during thawing by incremental dilution of serum to reduce oncotic shock, followed by washing and further culture in serum-free medium. When assessed with live/dead viability dyes, thawed microtissues demonstrated high viability but reduced immediate metabolic activity relative to unfrozen control microtissues. To further assess the functionality of the freeze-thawed microtissues, their capacity to amalgamate into a continuous tissue was assess over a 14 day culture. The amalgamation of microtissues cultured for 5 days was superior to those that had been cultured for 10 days. Critically, the capacity of cryopreserved microtissues to amalgamate into a continuous tissue in a subsequent 14-day culture was not compromised, suggesting that cryopreserved microtissues could amalgamate within a cartilage defect site. The quality ECM was superior when amalgamation was performed in a 2% O 2 atmosphere than a 20% O 2 atmosphere, suggesting that this process may benefit from the limited oxygen microenvironment within a joint. In summary, cryopreservation of cartilage microtissues is a viable option, and this manipulation can be performed without compromising tissue function., Competing Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: MRD and KF founded a company that seeks to commercialize the Microwell-mesh., (© The Author(s) 2023.)

For bone marrow stromal cells (BMSC) to be useful in cartilage repair their propensity for hypertrophic differentiation must be overcome. A single day of TGF-β1 stimulation activates intrinsic signaling cascades in BMSCs which subsequently drives both chondrogenic and hypertrophic differentiation. TGF-β1 stimulation upregulates SP7 , a transcription factor known to contribute to hypertrophic differentiation, and SP7 remains upregulated even if TGF-β1 is subsequently withdrawn from the chondrogenic induction medium. Herein, we stably transduced BMSCs to express an shRNA designed to silence SP7 , and assess the capacity of SP7 silencing to mitigate hypertrophy. SP7 silencing dampened both hypertrophic and chondrogenic differentiation processes, resulting in diminished microtissue size, impaired glycosaminoglycan production and reduced chondrogenic and hypertrophic gene expression. Thus, while hypertrophic features were dampened by SP7 silencing, chondrogenic differentation was also compromised. We further investigated the role of SP7 in monolayer osteogenic and adipogenic cultures, finding that SP7 silencing dampened characteristic mineralization and lipid vacuole formation, respectively. Overall, SP7 silencing affects the trilineage differentiation of BMSCs, but is insufficient to decouple BMSC hypertrophy from chondrogenesis. These data highlight the challenge of promoting BMSC chondrogenesis whilst simultaneously reducing hypertrophy in cartilage tissue engineering strategies., Competing Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: K.F. and M.R.D. co-founded a company, Microwell-mesh.com, to share the culture device described in this paper., (© The Author(s) 2023.)

Standard practice for acetabular component placement in total hip arthroplasty (THA) is to medialise the acetabular component. Bone preservation techniques during primary THA are beneficial for possible future revisions. The goal of this study is to examine the effect of downsizing and minimising medialisation of the acetabular component on bone resection volume. The volume of bone resected during acetabular preparation for different sizes of components was calculated and the volume of bone preserved by downsizing the cup was determined. Minimising medialisation of the acetabular component by 1-3 mm from the true floor was calculated. Absolute values and percentage of bone volume preserved when acetabular components are downsized or less medialised is presented. Downsizing the acetabular component by one size (2 mm) preserves between 2.6 cm 3 (size 40 vs 42) and 8.4 cm 3 (size 72 vs 74) of bone volume and consistently reduces resected bone volume by at least 35% (range 35.2%-37.5%). Similarly, reducing medialisation of a 56 mm acetabular cup (as an example of a commonly implanted component) by 3 mm reduces bone loss by 5.9 cm 3 - 44% less bone volume resection. Downsizing and minimising medialisation of the cup in THA substantially preserves bone which may benefit future revision surgeries. Surgeons could consider implanting the smallest acceptable acetabular shell to preserve bone without compromising on head size.

Background: Total hip arthroplasty aims to provide patients with a pain-free and stable hip joint through optimization of biomechanics such as femoral anteversion. There are studies evaluating the limits of cementless stem version, however, none assessing the range of version achieved by a cemented collarless stem. A computed tomography (CT)-based study was performed, utilizing a contemporary robotic planning platform to assess the amount of rotation afforded by a cemented collarless stem, whilst maintaining native biomechanics., Methods: The study utilized 36 cadaveric hips. All had CT scans of the pelvis and hip joints. The CT scans were then loaded into a contemporary robotic planning platform. A stem that restored the patients native femoral offset was selected and positioned in the virtual femur. The stem was rotated while checking for cortical contact at the level of the neck cut. Cortical contact was regarded as the rotation limit, assessed in both anteversion and retroversion. Target range for stem anteversion was 10°-20°. Failure to achieve target version triggered a sequence of adjustments to simulate surgical decisions., Results: Native femoral offset and target version range was obtained in 29 of 36 (80.5%) cases. Following an adjustment sequence, 4 further stems achieved target anteversion with a compromise in offset of 2.3 mm. Overall 33 of 36 (91.7%) stems achieved the target anteversion range of 10°-20°., Conclusions: Target femoral stem anteversion can be achieved using a cemented, collarless stem in a CT-based 3-dimensional model in 80.5% of hips. With a small compromise in offset (mean 2.3 mm), this can be increased to 91.7%., (© 2022 The Authors.)

Bone morphogenetic protein (BMP) cascades are upregulated during bone marrow-derived stromal cell (BMSC) chondrogenesis, contributing to hypertrophy and preventing effective BMSC-mediated cartilage repair. Previous work demonstrated that a proprietary BMP inhibitor prevented BMSC hypertrophy, yielding stable cartilage tissue. Because of the significant therapeutic potential of a molecule capable of hypertrophy blockade, we evaluated the capacity of a commercially available BMP type I receptor inhibitor with similar properties, LDN 193189, to prevent BMSC hypertrophy. Using 14-day microtissue chondrogenic induction cultures we found that LDN 193189 permitted BMSC chondrogenesis but did not prevent hypertrophy. LDN 193189 was sufficiently potent to counter mineralization and adipogenesis in response to exogenous BMP-2 in osteogenic induction cultures. LDN 193189 did not modify BMSC behavior in adipogenic induction cultures. Although LDN 193189 is effective in countering BMP signaling in a manner that influences BMSC fate, this blockade is insufficient to prevent hypertrophy., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

When repairing cartilage defects a major challenge is achieving high-quality integration between the repair tissue and adjacent native cartilage. Matrix-rich cartilage is not easily remodeled, motivating several studies to trial enzyme treatment of the tissue interface to facilitate remodeling and integration. Studying and optimizing such processes is tedious, as well as potentially expensive, and thus simpler models are needed to evaluate the merits of enzyme treatment on cartilage tissue integration. Herein, we used engineered cartilage microtissues formed from bone marrow-derived stromal cells (BMSC) or expanded articular chondrocytes (ACh) to study the impact of enzyme treatment on cartilage tissue integration and matrix remodeling. A 5-min treatment with collagenase appeared to improve cartilage microtissue integration, while up to 48 h treatment with hyaluronidase did not. Alcian blue and anti-collagen II staining suggested that collagenase treatment did facilitate near seamless integration of cartilage microtissues. Microtissue sections were stained with Picrosirius red and characterized using polarized light microscopy, revealing that individual microtissues contained a collagen network organized in concentric shells. While collagenase treatment appeared to improve tissue integration, assessment of the collagen fibers with polarized light indicated that enzymatically damaged networks were not remodeled nor restored during subsequent culture. This model and these data paradoxically suggest that collagen network disruption is required to improve cartilage tissue integration, but that the disrupted collagen networks are unlikely to subsequently be restored. Future studies should attempt to limit collagen network disruption to the surface of the cartilage, and we recommend using Picrosirius red staining and polarized light to assess the quality of matrix remodeling and integration., Competing Interests: Declaration of conflicting interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2022.)

We present a global atlas of 4,728 metagenomic samples from mass-transit systems in 60 cities over 3 years, representing the first systematic, worldwide catalog of the urban microbial ecosystem. This atlas provides an annotated, geospatial profile of microbial strains, functional characteristics, antimicrobial resistance (AMR) markers, and genetic elements, including 10,928 viruses, 1,302 bacteria, 2 archaea, and 838,532 CRISPR arrays not found in reference databases. We identified 4,246 known species of urban microorganisms and a consistent set of 31 species found in 97% of samples that were distinct from human commensal organisms. Profiles of AMR genes varied widely in type and density across cities. Cities showed distinct microbial taxonomic signatures that were driven by climate and geographic differences. These results constitute a high-resolution global metagenomic atlas that enables discovery of organisms and genes, highlights potential public health and forensic applications, and provides a culture-independent view of AMR burden in cities., Competing Interests: Declaration of interests C.E.M. is co-founder of Biotia and Onegevity Health. D.B. is co-founder and CSO of Poppy Health Inc. The other authors declare they have no competing interests that impacted this study., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Virtually all bone marrow-derived stromal cell (BMSC) chondrogenic induction cultures include greater than 2 weeks exposure to transforming growth factor-β (TGF-β), but fail to generate cartilage-like tissue suitable for joint repair. Herein we used a micro-pellet model (5 × 10 3 BMSC each) to determine the duration of TGF-β1 exposure required to initiate differentiation machinery, and to characterize the role of intrinsic programming. We found that a single day of TGF-β1 exposure was sufficient to trigger BMSC chondrogenic differentiation and tissue formation, similar to 21 days of TGF-β1 exposure. Despite cessation of TGF-β1 exposure following 24 hours, intrinsic programming mediated further chondrogenic and hypertrophic BMSC differentiation. These important behaviors are obfuscated by diffusion gradients and heterogeneity in commonly used macro-pellet models (2 × 10 5 BMSC each). Use of more homogenous micro-pellet models will enable identification of the critical differentiation cues required, likely in the first 24-hours, to generate high quality cartilage-like tissue from BMSC.

Background: Total hip arthroplasty (THA) is an effective procedure for relieving pain and restoring function in osteoarthritis. A significant proportion of patients have severe disease bilaterally. Consensus regarding safety and selection of patients for simultaneous bilateral THA or the optimal timing for staged THA has not been reached. The aim of this study is to compare rates, causes of revision, and 30-day mortality between simultaneous and staged bilateral THA using data from the Australian Orthopedic National Joint Replacement Registry., Methods: Data for 12,359 bilateral THA procedures were collected from September, 1999 to December, 2017. Rates and causes of revision and 30-day mortality were obtained for simultaneous bilateral and staged procedures with intervals of 1 day-6 weeks, 6 weeks-3 months, and 3 months-6 months. Yearly cumulative percent revision or cumulative percent survival with 95% confidence intervals calculated by the Kaplan-Meier method, and adjusted hazard ratios were used for comparisons., Results: Thirty-day mortality is lower in patients who have bilateral procedures within 6 months, regardless of timing, than those who have unilateral procedures (0.06% vs 0.18%). Staged bilateral THA had a significantly lower mortality than simultaneous bilateral THA (odds ratio 0.175, 95% confidence interval = 0.04-0.78, P = .022). When separate time intervals were compared, no significant differences were seen. Bilateral 6 week-3 months has a higher rate of revision from 1.5 years-2years compared with same day bilaterals (hazard ratio = 2.39, 95% confidence interval = 1.12, 5.09, P = .024). There were no other significant differences in the rate of revision between groups. The most common reasons for revision were fracture, loosening, and infection. Simultaneous bilateral procedures have a significantly higher rate of revision for fracture compared with staging 3-6 months (hazard ratio = 1.96 [1.27, 3.03], P = .002)., Conclusion: This study demonstrates that bilateral THA has a low mortality rate regardless of time interval between procedures. Simultaneous and staged bilateral THA have similar rates of revision., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Hip arthroplasty is increasing in Australia. The number of procedures for fractured neck of femur was 7500 in 2017. Best practices for fixation method and procedure type require scrutiny. This paper is about the costs and health outcomes of cemented and uncemented hemiarthroplasty and total hip arthroplasty at a national level., Methods: We created a Markov model for patients <75, aged 75-85, and over 85. Expected costs and health outcomes over 5 years from a decision to change from existing practice to a best practice policy in which all patients with fractured neck of femur received the same fixation method based on age and type of arthroplasty are estimated. The model was populated using prevalence and incidence data from the Australian Orthopedic Association National Joint Replacement Registry, costs from Metro North Hospital and Health Service in Queensland, and probabilities and utilities from the literature. We simulated the uncertainties in outcomes with probabilistic sensitivity analysis., Results: We found that uncemented stem procedures were more costly and provided worse health outcomes compared to cemented stem fixation for hemiarthroplasty and total hip arthroplasty for all age groups. Moving from existing practice to cemented stem arthroplasty could save the Australian health system $2.0 million over 5 years with a gain of 203 quality-adjusted life years., Conclusion: We suggest that consideration be given to cemented fixation of the femoral stem for patients receiving both hemiarthroplasty and total hip arthroplasty for fractured neck of femur. Best practice guidelines focused on cost-effectiveness should recommend cemented stem fixation to both save costs and improve patient quality of life., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: To review on-table, day 0, day 1, day 7, and day 30 mortality after hemiarthroplasty or total hip arthroplasty (THA) using cemented femoral stems for femoral neck fractures in order to evaluate risk factors for perioperative and short-term mortality., Methods: The medical records of 751 consecutive cases with neck of femur fractures who underwent hemiarthroplasty (n = 602) or THA (n = 149) with cemented stems between January 2011 and December 2016 were retrospectively reviewed from a prospectively gathered database. The primary outcome measures were on-table, day 0, day 1, day 7, and day 30 mortality. Univariate and multivariate analyses were performed in order to identify various contributing patient and surgical variables., Results: There were 2 on-table deaths (0.27%): one patient had a cardiorespiratory arrest at the time of inserting the femoral stem and the other had a cardiorespiratory arrest at the end of wound closure some 20 minutes after cementing. There were 3 further day 0 deaths meaning the day 0 mortality rate was 0.67% (5/751). All 5 patients were older than 80 years and had an American Society of Anesthesiologists grade 3 or more. The 1-day, 7-day, and 30-day mortality rates were 0.93% (7 patients), 2.7% (20 patients), and 6.8% (51 patients), respectively. There is significantly higher 30-day mortality risk associated with increasing American Society of Anesthesiologists grade (P < .001) when adjusted for age, gender, and type of surgery (hemiarthroplasty compared with THA)., Conclusion: In our neck of femur fracture patients who were operated with cemented stems, 7-day and 30-day mortality rates were 2.7% and 6.8%, respectively. Cemented stems should be used with caution in elderly hip fracture patients with multiple comorbidities who are at high risk of perioperative mortality., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Soft tissue balancing while crucial for a successful total knee arthroplasty (TKA) is incompletely defined and the subject of broad recommendations. We analyzed 69 unilateral computer-assisted surgery posterior stabilized (PS) TKA subjects who postoperatively scored ≥36 out of a possible 40 points on the satisfaction section of the American Knee Society score (2011). We examined a range of postoperative coronal plane laxity parameters and the correlation between preoperative and postoperative laxity. Total postoperative coronal laxity arcs at maximum extension and 20 degrees of flexion varied between 2 and 12 and 3 and 13 degrees, respectively. Depending on the position of measurement, medial laxity was between 0.5 and 9.5 degrees and lateral laxity between 1 and 12 degrees. The change in laxity between maximum extension and 90 degrees of flexion demonstrated a range of 7 degrees medially and 12 degrees laterally. The total coronal arc of movement did not affect functional outcomes. A moderate correlation of 0.452 and 0.424 was seen between initial and postoperative total coronal laxity arcs in maximum extension and 20 degrees of flexion, respectively. The individual variability for each measured parameter within our cohort demonstrates TKA satisfaction is not as simple as producing a narrow range of coronal laxity parameters and that as with many body systems considerable variation is still consistent with excellent function. Our findings help to define acceptable balance parameters for PS TKA. It does not appear necessary to closely match postoperative laxity to that present preoperatively., Competing Interests: S.L.W. reports other from Stryker Corp, outside the submitted work., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

We aimed to describe the epidemiology, multi-drug resistance and seasonal distribution of bacteria cultured within 12 months following lower limb orthopaedic surgery in tropical and subtropical Australian hospitals between 2010 and 2017. We collected data from four tropical and two subtropical hospitals. Categorical variables were examined using the Pearson Chi-squared test or Fisher's Exact test, and continuous variables with the Student t-test or Mann-Whitney U test. A Poisson regression model was used to examine the relationship between season, weather and the incidence of Staphylococcus and nonfermentative species. We found that at tropical sites, nonfermenters ( Pseudomonas aeruginosa and Acinetobacter baumannii ) were more common (28.7% vs. 21.6%, p = 0.018), and patients were more likely to culture multi-drug-resistant (MDR) nonfermenters (11.4% vs. 1.3%, p = 0.009) and MDR Staphylococcus aureus (35.9% vs. 24.6%, p = 0.006). At tropical sites, patients were more likely to be younger (65.9 years vs. 72.0, p = < 0.001), male (57.7% vs. 47.8%, p = 0.005), having knee surgery (45.3% vs. 34.5%, p = 0.002) and undergoing primary procedures (85.0% vs. 73.0%, p = < 0.001). Species were similar between seasons in both tropical and subtropical hospitals. Overall, we found that following lower limb orthopaedic surgery in tropical compared with subtropical Australia, patients were more likely to culture nonfermenters and some MDR species.

Background: Patellar resurfacing in total knee arthroplasty (TKA) remains a controversial issue after more than 4 decades of TKA. Despite a growing body of evidence from registry data, resurfacing is still based largely on a surgeon's preference and training. The purpose of this study is to provide long-term outcomes for patellar resurfaced compared to when the patella is not resurfaced., Methods: Data from the Australian Orthopaedic Association National Joint Replacement Registry (1999-2017) were used for this study. The analysis included 570,735 primary TKAs undertaken for osteoarthritis. Hazard ratios (HRs) and 17-year cumulative percent revision rates were used to compare revision rates between 4 subgroups: minimally stabilized (MS) patellar resurfacing, posterior stabilized (PS) patellar resurfacing, MS unresurfaced, and PS unresurfaced patella. Additional analyses of the patellar implant type and a comparison of inlay and onlay patellar resurfacing were also performed., Results: For all primary TKA, procedures where the patella was not resurfaced have a higher rate of revision compared to procedures where the patella was resurfaced (HR, 1.31; confidence interval, 1.28-1.35; P < .001). Unresurfaced PS knees have the highest cumulative percent revision at 17 years (11.1%), followed by MS unresurfaced (8.8%), PS resurfaced (7.9%), and MS resurfaced (7.1%). Inlay patellar resurfacing has a higher rate of revision compared to onlay patellar resurfacing (HR, 1.27; confidence interval, 1.17-1.37; P < .001)., Conclusion: Resurfacing the patella reduces the rate of revision for both MS and PS knees. MS knees with patellar resurfacing have the lowest rate of revision. Onlay patella designs are associated with a lower revision rate compared to inlay patella designs., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Introduction: Many infectious diseases display seasonal variation corresponding with particular conditions. In orthopaedics a growing body of evidence has identified surges in post-operative infection rates during higher temperature periods. The aim of this research was to collate and synthesize the current literature on this topic., Methods: A systematic review and meta-analysis was performed using five databases (PubMed, Embase, CINAHL, Web of Science and Central (Cochrane)). Study quality was assessed using the Grading of Recommendations Assessment, Development and Evaluation method. Odds ratios (ORs) were calculated from monthly infection rates and a pooled OR was generated using the DerSimonian and Lairds method. A protocol for this review was registered with the National Institute for Health Research International Prospective Register of Systematic Reviews (CRD42017081871)., Results: Eighteen studies analysing over 19 000 cases of orthopaedic related infection met inclusion criteria. Data on 6620 cases and 9035 controls from 12 studies were included for meta-analysis. The pooled OR indicated an overall increased odds of post-operative infection for patients undergoing orthopaedic procedures during warmer periods of the year (pooled OR 1.16, 95% confidence interval 1.04-1.30)., Conclusion: A small but significantly increased odds of post-operative infection may exist for orthopaedic patients who undergo procedures during higher temperature periods. It is hypothesized that this effect is geographically dependent and confounded by meteorological factors, local cultural variables and hospital staffing cycles., (© 2019 Royal Australasian College of Surgeons.)

Background: The declining popularity of cemented acetabular components is incongruous, given the published results of prostheses implanted using contemporary techniques. The outcome of arthroplasty has previously been demonstrated to correlate with surgeon experience and volume of practice. We aim to explore if surgeon volume alters outcomes of cemented acetabular components based on survivorship data from the Australian Orthopaedic Association National Joint Replacement Registry (AOANJRR)., Methods: An observational study was undertaken using a cohort of 22,956 patients with a primary diagnosis of osteoarthritis in the period 2003-2016 in whom cemented acetabular components were implanted. The cohort was stratified by age (greater than or less than 65 years) and annualized surgical volume of ≤10, >10-≤25, and >25 cases., Results: Stratified by age and volume, there was a protective benefit against revision conveyed at volume thresholds of 10 cases per annum and 25 cases per annum for patients ≥65 years of age and <65 years of age, respectively., Conclusion: Cemented total hip arthroplasty has excellent survivorship out to 15 years based on AOANJRR data. This survivorship is further improved if surgeons perform a higher volume of cases, with >25 cases conferring the greatest benefit. The AOANJRR data set is used to define best practice; surgeons who choose to utilize cemented acetabular fixation should be encouraged to perform this technique in adequate volumes to minimize revision risk and ensure the preservation of this important surgical skill set., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Diabetic foot ulcers represent a significant source of morbidity in the U.S., with rapidly escalating costs to the health care system. Multiple pathophysiological disturbances converge to result in delayed epithelialization and persistent inflammation. Serotonin (5-hydroxytryptamine [5-HT]) and the selective serotonin reuptake inhibitor fluoxetine (FLX) have both been shown to have immunomodulatory effects. Here we extend their utility as a therapeutic alternative for nonhealing diabetic wounds by demonstrating their ability to interact with multiple pathways involved in wound healing. We show that topically applied FLX improves cutaneous wound healing in vivo. Mechanistically, we demonstrate that FLX not only increases keratinocyte migration but also shifts the local immune milieu toward a less inflammatory phenotype in vivo without altering behavior. By targeting the serotonin pathway in wound healing, we demonstrate the potential of repurposing FLX as a safe topical for the challenging clinical problem of diabetic wounds., (© 2019 by the American Diabetes Association.)

Background: Computer navigation and image-derived instrumentation (IDI) are technology-based methods developed to improve outcomes and potentially reduce revision total knee arthroplasty (TKA). IDI refers to the use of manufactured, patient-specific surgical jigs. Conflicting reports exist on IDI-associated improvements in outcomes. The primary aim of the current study was to compare the rates of revision among TKA cases in which components were initially implanted with use of IDI, computer navigation, or neither of these methods ("other" TKA). The secondary aim was to determine whether the outcomes of IDI differed for specific subgroups., Methods: Data were obtained from the Australian Orthopaedic Association National Joint Replacement Registry (AOANJRR) for the 3 TKA groups: IDI, computer-navigated, and other TKA. The study period was from the first IDI procedure recorded by the AOANJRR (April 2010) to December 31, 2016. The analysis was restricted to primary TKA cases undertaken for osteoarthritis and involving patellar resurfacing and the use of a cross-linked polyethylene insert. Subanalyses were performed to evaluate the effects of age, sex, implantation method, IDI manufacturer, prosthetic design, and prosthesis type on the rates of revision. Kaplan-Meier estimates of survivorship described the time to first revision. Hazard ratios (HRs, Cox proportional hazards models) with adjustment for age and sex were used to compare revision rates., Results: IDI was used in 5,486 primary TKA procedures. There was no significant difference among the groups in the cumulative percent revision (CPR) at 5 years: 3.3% (95% confidence interval [CI], 2.4% to 4.6%) for IDI, 2.4% (95% CI, 2.2% to 2.7%) for the computer-navigated group, and 2.5% (95% CI, 2.3% to 2.7%) for other TKA. Posterior-stabilized TKA with use of the IDI method had a significantly higher rate of revision at >3 months (HR, 1.45 [95% CI, 1.02 to 2.04]; p = 0.036), as did IDI TKA in the ≤65-year-old patient cohort (HR, 1.52 [95% CI, 1.10 to 2.09]; p = 0.010), compared with computer-navigated TKA. Patellar revision was significantly more likely in the IDI group., Conclusions: IDI TKA demonstrated no overall difference in early to mid-term revision rates compared with standard implantation methods. However, elevated rates of revision were seen with posterior-stabilized TKA, in patients ≤65 years of age, and for patellar revision, meaning that this method should be used with some caution and requires further study., Level of Evidence: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

When a bone substitute biomaterial is implanted into the body, the material's surface comes into contact with circulating blood, which results in the formation of a peri-implant hematoma or blood clot. Although hematoma formation is vital for the early bone healing process, knowledge concerning the biomaterial-induced structural properties of blood clots is limited. Here, we report that implantation of beta-tricalcium phosphate (β-TCP) in a bone defect healing model in rats resulted in significantly delayed early bone healing compared to empty controls (natural healing). In vitro studies showed that β-TCP had a profound effect on the overall structure of hematomas, as was observed by fibrin turbidity, scanning electron microscopy (SEM), compaction assays, and fibrinolysis. Under the influence of β-TCP, clot formation had a significantly shortened lag time and there was enhanced lateral fibrin aggregation during the clot polymerization, which resulted in clots composed of thinner fibers. Furthermore, fibrin clots that formed around β-TCP exhibited reduced compaction and increased resistance to fibrinolysis. Together, these results provide a plausible mechanism for how implanted bone-substitute materials may impact the structural properties of the hematoma, thereby altering the early bone healing processes, such as cell infiltration, growth factor release and angiogenesis.

Background: The influence of obesity measured in terms of body mass index (BMI) on the complication rates following total hip arthroplasty (THA) is a matter of debate., Methods: This retrospective study conducted at a tertiary referral centre at Brisbane, Australia, examines the association between BMI and in-hospital postoperative complications, length of operating time and duration of hospital stay in 964 patients, who underwent THA from 2006 to 2010., Results: Amongst patients undergoing primary THA, when compared to the normal weight patients, those with BMI between 25 kg/m 2 and 29.9 kg/m 2 (overweight) and those with BMI between 35 kg/m 2 and 39.9 kg/m 2 (obese class II) had lower odds of perioperative complications (odds ratio [OR]: 0.62 (95% confidence intervals [CI], 0.43-0.92, p = 0.016) and OR: 0.60 (95% CI, 0.36- 0.99, p = 0.047 respectively). Patients with BMI less than or equal to 40 kg/m 2 were also associated with significantly lower odds of cardiac complications ( p = 0.02). With unadjusted regression analysis, it was noted that those with BMI ≥40 kg/m 2 had the highest odds of developing infectious complications (OR 2.68, 95% CI, 1.08-6.65, p < 0.05). As the BMI increased, there was a statistically significant increase in length of operating time ( p < 0.001)., Conclusion: There is a significant impact of BMI on the occurrence of perioperative complications following THA. Compared to normal weight category, the overweight and obese class II patients had a lower likelihood of developing overall, especially cardiac complications. Length of operating time increases along with an increase in BMI.

Background: Total knee arthroplasty (TKA) is an effective procedure for relieving pain and restoring function in osteoarthritis, with a significant proportion of patients having severe disease bilaterally. However, although there are differences in patient selection criteria for bilateral procedures, there is no consensus regarding the optimal timing for bilateral TKA. The aim of this study was to compare rates and causes of revision and 30-day mortality between simultaneous and staged bilateral TKA using data from the Australian Orthopaedic Association National Joint Replacement Registry., Methods: Data for over 36,000 bilateral TKAs were collected from September 1999 to December 2015. Rates and causes of revision and 30-day mortality rates were obtained for simultaneous bilateral and staged procedures with intervals of 1 day-6 weeks, 6 weeks-3 months, and 3-6 months. Yearly cumulative percent revision or cumulative percent survival with 95% confidence intervals calculated using the Kaplan-Meier method and adjusted hazard ratios were used for comparisons., Results: There was no significant difference between revision rates or reasons for revision between staged bilateral and simultaneous TKA (hazard ratio 1.09 [95% confidence interval {CI} 0.85-1.40; P = .511] for 1 day-6 weeks, 0.93 [95% CI 0.77-1.14; P = .494] for 6 weeks-3 months, and 1.10 [95% CI 0.98-1.23; P = .115] for 3-6 months). The most common reasons for revision were loosening/lysis and infection. The 30-day mortality rates were lower in the 6 weeks-3 months group than simultaneous bilaterals (P = .007)., Conclusion: This study demonstrates that simultaneous and staged bilateral TKA have similar rates of revision over the medium term but that 30-day mortality is reduced in the 6 weeks-3 months group., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: The role of space suits in the prevention of orthopedic prosthetic joint infection remains unclear. Recent evidence suggests that space suits may in fact contribute to increased infection rates, with bioaerosol emissions from space suits identified as a potential cause. This study aimed to compare the particle and microbiological emission rates (PER and MER) of space suits and standard surgical clothing., Methods: A comparison of emission rates between space suits and standard surgical clothing was performed in a simulated surgical environment during 5 separate experiments. Particle counts were analyzed with 2 separate particle counters capable of detecting particles between 0.1 and 20 μm. An Andersen impactor was used to sample bacteria, with culture counts performed at 24 and 48 hours., Results: Four experiments consistently showed statistically significant increases in both PER and MER when space suits are used compared with standard surgical clothing. One experiment showed inconsistent results, with a trend toward increases in both PER and MER when space suits are used compared with standard surgical clothing., Conclusion: Space suits cause increased PER and MER compared with standard surgical clothing. This finding provides mechanistic evidence to support the increased prosthetic joint infection rates observed in clinical studies., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Purpose: To investigate the association between body mass index (BMI) and perioperative complications until hospital discharge, following primary total knee arthroplasty (TKA)., Methods: This retrospective study reviewed 1665 cases of elective primary unilateral TKA performed between 2006 and 2010, from a prospective secure electronic database. Types of complications, length of operating time, and duration of hospital stay were analyzed in both adjusted (for known confounders) and unadjusted analyses. A further matched analysis was also performed., Results: In terms of overall complications, there was no statistically significant difference between the BMI categories. When individual obesity category was considered, obese 2 had the lowest odds of developing complications, both with unadjusted (odds ratio (OR): 0.61, 95% confidence interval (CI) 0.41-0.91, p < 0.015) and adjusted regression analysis (OR: 0.65, 95% CI: 0.43-0.99, p = 0.044). Compared to normal weight category, obese class 3 (≥40 kg/m 2 ) individuals were at 66% (OR: 0.34, 95% CI: 0.21-0.55) lower (unadjusted) odds of developing cardiac complications (overall p < 0.001). With the matched analysis, compared to normal weight category, obese class 3 (≥40 kg/m 2 ) individuals were at a 60% (OR: 0.40, 95% CI: 0.23-0.68) lower (unadjusted) odds of developing cardiac complications (overall p = 0.004). Obese 3 patients had significantly higher operating time compared with other groups ( p < 0.001)., Conclusion: This study did not find a significant association between BMI and increased overall in-hospital medical or surgical complications following primary TKA. Obesity significantly increased the length of operating time.

Of the many cell-based treatments that have been tested in an effort to regenerate osteoarthritic articular cartilage, none have ever produced cartilage that compare with native hyaline cartilage. Studies show that different cell types lead to inconsistent results and for cartilage regeneration to be considered successful, there must be an absence of fibrotic tissue. Here we report of a series of experiments in which bone marrow-derived stem cells (BMSCs) and articular cartilage chondrocytes (ACCs) were mixed in a 1:1 ratio and tested for their ability to enhance cartilage regeneration in three different conditions: (1) in an in vitro differentiation model; (2) in an ex vivo cartilage defect model implanted subcutaneously in mice; and (3) as an intra-articular injection in a meniscectomy-induced OA model in rats. The mixed cells were compared with monocultures of BMSCs and ACCs. In all three experimental models there was significantly enhanced cartilage regeneration and decreased fibrosis in the mixed BMSCs+ACCs group compared with the monocultures. Molecular analysis showed a reduction in vascularization and hypertrophy, coupled with higher chondrogenic gene expression resulting from the BMSCs+ACCs treatment. Together, our data suggest that mixed BMSCs+ACCs treatment is highly chondro-protective and is more effective in regenerating damaged cartilage in both the ex vivo cartilage defect and post-trauma OA disease models. The results from this approach could potentially be used for regeneration of cartilage in OA patients.