A tumour-spheroid manufacturing and cryopreservation process that yields a highly reproducible product ready for direct use in drug screening assays.

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.

Three-Dimensional CT-Based Limb Length Evaluation Is Highly Dependent on Anatomical Landmark Selection and Pelvic Asymmetry.

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.

Method for manufacture and cryopreservation of cartilage microtissues.

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% O2 atmosphere than a 20% O2 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.

SP7 gene silencing dampens bone marrow stromal cell hypertrophy, but it also dampens chondrogenesis.

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-ß1 stimulation activates intrinsic signaling cascades in BMSCs which subsequently drives both chondrogenic and hypertrophic differentiation. TGF-ß1 stimulation upregulates SP7, a transcription factor known to contribute to hypertrophic differentiation, and SP7 remains upregulated even if TGF-ß1 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.

Downsizing and minimising medialisation of the acetabular component: Novel technique to preserve bone in THA.

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 cm3 (size 40 vs 42) and 8.4 cm3 (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 cm3- 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.

Achieving Target Cemented Femoral Stem Anteversion Using a 3-Dimensional Model.

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%.

Microtissue Culture Provides Clarity on the Relative Chondrogenic and Hypertrophic Response of Bone-Marrow-Derived Stromal Cells to TGF-ß1, BMP-2, and GDF-5.

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-ß)/bone morphogenetic factor (BMP) superfamily. In a previous study, we demonstrated that brief (1-3 days) stimulation with TGF-ß1 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-ß1 (10 ng/mL). Like TGF-ß1, 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-ß1 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-ß1 > BMP-2 > GDF-5. Whether briefly or continuously supplied in culture, TGF-ß1 was the most potent GF for inducing chondrogenesis in BMSCs.

The Cost Effectiveness of Unicompartmental versus Total Knee Arthroplasty.

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.

Inhibition of BMP signaling with LDN 193189 can influence bone marrow stromal cell fate but does not prevent hypertrophy during chondrogenesis.

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.

Collagenase treatment appears to improve cartilage tissue integration but damage to collagen networks is likely permanent.

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.

A single day of TGF-ß1 exposure activates chondrogenic and hypertrophic differentiation pathways in bone marrow-derived stromal cells.

Virtually all bone marrow-derived stromal cell (BMSC) chondrogenic induction cultures include greater than 2 weeks exposure to transforming growth factor-ß (TGF-ß), but fail to generate cartilage-like tissue suitable for joint repair. Herein we used a micro-pellet model (5 × 103 BMSC each) to determine the duration of TGF-ß1 exposure required to initiate differentiation machinery, and to characterize the role of intrinsic programming. We found that a single day of TGF-ß1 exposure was sufficient to trigger BMSC chondrogenic differentiation and tissue formation, similar to 21 days of TGF-ß1 exposure. Despite cessation of TGF-ß1 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 × 105 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.

Mortality and Implant Survival With Simultaneous and Staged Bilateral Total Hip Arthroplasty: Experience From the Australian Orthopedic Association National Joint Replacement Registry.

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.

Fixation Method for Hip Arthroplasty Stem Following Hip Fracture: A Population-Level Cost-Effectiveness Analysis.

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.

Bacterial Profile, Multi-Drug Resistance and Seasonality Following Lower Limb Orthopaedic Surgery in Tropical and Subtropical Australian Hospitals: An Epidemiological Cohort Study.

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.

Highly Satisfied Total Knee Arthroplasty Patients Display a Wide Range of Soft Tissue Balance.

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.

The Outcome of Total Knee Arthroplasty With and Without Patellar Resurfacing up to 17 Years: A Report From the Australian Orthopaedic Association National Joint Replacement Registry.

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.

On-Table and Short-Term Mortality: A Single-Institution Experience With Cementing All Hip Arthroplasties for Neck of Femur Fractures.

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.

Association between higher ambient temperature and orthopaedic infection rates: a systematic review and meta-analysis.

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.