Patients with knee osteoarthritis have altered gait and gaze patterns compared to age-matched controls: A pilot study.

PURPOSE: Although knee Osteoarthritis (KOA) sufferers are at an increased risk of falls, possibly due to impaired gait function, the associated gaze behaviour in patients with KOA are largely unknown. Thus, we compared gait and gaze behaviours characteristics between KOA patients and asymptomatic age-matched controls. RESULTS: For Timed Up and Go (TUG) and stair climb tasks, the KOA group demonstrated longer periods of gaze fixations with less frequency of fixations compared to the control group. Conversely, for the Timed up and Go Agility (TUGA) test shorter fixation and frequency patterns were observed. The KOA group presented a shorter final stride length prior to the initiation of the first step in the Stair climb assessment. In addition, for the 30m walk and dual task assessments, the average step length was significantly shorter in the KOA group compared to controls. CONCLUSION: Overall, we found altered gait and gaze behaviours are evident in KOA patients which could relate to their increased falls risk.

Navigated functional alignment total knee arthroplasty achieves reliable, reproducible and accurate results with high patient satisfaction.

PURPOSE: The decision on which technique to perform a total knee arthroplasty (TKA) has become more complicated over the last decade. Perceived limitations of mechanical alignment (MA) and kinematic alignment (KA) have led to the development of the functional alignment (FA) philosophy. This study aims to report the 2-year results of an initial patient cohort in terms of revision rate, PROMs and complications for Computer Aided Surgery (CAS) Navigated FA TKA. METHODS: This paper reports a single surgeon's outcomes of 165 consecutive CAS FA TKAs. The final follow-up was 24 months. Pre-operative and post-operative patient-reported outcome measures, WOMAC and KSS, and intra-operative CAS data, including alignment, kinematic curves, and gaps, are reported. Stress kinematic curves were analysed for correlation with CAS final alignment and CAS final alignment with radiographic long-leg alignment. Pre- and post-operative CPAK and knee phenotypes were recorded. Three different types of prostheses from two manufacturers were used, and outcomes were compared. Soft tissue releases, revision and complication data are also reported. RESULTS: Mean pre-operative WOMAC was 48.8 and 1.2 at the time of the final follow-up. KSS was 48.8 and 93.7, respectively. Pre- and post-operative range of motion was 118.6° and 120.1°, respectively. Pre-operative and final kinematic curve prediction had an accuracy of 91.8%. CAS data pre-operative stress alignment and final alignment strongly correlate in extension and flexion, r = 0.926 and 0.856, p < 0.001. No statistical outcome difference was detected between the types of prostheses. 14.5% of patients required soft tissue release, with the lateral release (50%) and posterior capsule (29%) being the most common. CONCLUSION: CAS FA TKA in this cohort proved to be a predictable, reliable, and reproducible technique with acceptable short-term revision rates and high PROMs. FA can account for extremes in individual patient bony morphology and achieve desired gap and kinematic targets with soft tissue releases required in only 14.5% of patients. LEVEL OF EVIDENCE: IV (retrospective case series review).

Digital TKA Alignment Training with a New Digital Simulation Tool (Knee-CAT) Improves Process Quality, Efficiency, and Confidence.

Individual alignment techniques have been introduced to restore patients' unique anatomical variations during total knee arthroplasty. The transition from conventional mechanical alignment to individualised approaches, with the assistance of computer and/or robotic technologies, is challenging. The objective of this study was to develop a digital training platform with real patient data to educate and simulate various modern alignment philosophies. The aim was to evaluate the training effect of the tool by measuring the process quality and efficiency, as well as the post-training surgeon's confidence with new alignment philosophies. Based on 1000 data sets, a web-based interactive TKA computer navigation simulator (Knee-CAT) was developed. Quantitative decisions on bone cuts were linked to the extension and flexion gap values. Eleven different alignment workflows were introduced. A fully automatic evaluation system for each workflow, with a comparison function for all workflows, was implemented to increase the learning effect. The results of 40 surgeons with different experience levels using the platform were assessed. Initial data were analysed regarding process quality and efficiency and compared after two training courses. Process quality measured by the percentage of correct decisions was increased by the two training courses from 45% to 87.5%. The main reasons for failure were wrong decisions on the joint line, tibia slope, femoral rotation, and gap balancing. Efficiency was obtained with a reduction in time spent per exercise from 4 min 28 s to 2 min 35 s (42%) after the training courses. All volunteers rated the training tool as helpful or extremely helpful for learning new alignment philosophies. Separating the learning experience from OR performance was mentioned as one of the main advantages. A novel digital simulation tool for the case-based learning of various alignment philosophies in TKA surgery was developed and introduced. The simulation tool, together with the training courses, improved surgeon confidence and their ability to learn new alignment techniques in a stress-free out-of-theatre environment and to become more time efficient in making correct alignment decisions.

Mismatch between trochlear coronal alignment of arthritic knees and currently available prosthesis: a morphological analysis of 4116 knees and 45 implant designs.

PURPOSE: In up to a fifth of total knee replacements (TKR), surgeons are not capable of achieving good clinical and functional results. Despite comprehensive diagnostic workup, an underlying cause is not always identified in these patients. The purpose of this study is to compare native and prosthetic trochlear anatomies, to evaluate a potential source of morphologic mismatch and theoretically, of poor clinical outcomes. METHODS: Native trochlear angles of 4116 knee CTs from 360 Knee Systems database of arthritic pre-operative TKR patients were evaluated. A semi-automated tridimensional analysis was performed to define the native trochlear angle in the coronal plane (NTA) among other 142 parameters. An active search was conducted to identify currently available TKR models; prosthetic trochlear orientation in the coronal plane (PTA) was extracted from the technical data provided by manufacturers. RESULTS: The mean native trochlear angle (NTA) was 1.6° ± 6.6° (valgus) with a range from - 23.8° (varus) to 30.3°(valgus). A valgus NTA was present in 60.6% of the knees and 39.4% of them had a varus NTA. 89 TKR models were identified; trochlear details were available for 45 of them, of which 93% were designed with a valgus orientation of the prosthetic trochlear angle (PTA) and 6.9% showed a neutral (0°) PTA. Varus alignment of PTA was not present in any system. Angular numeric values for PTA were available for 34 models; these ranged from 0° to 15° of valgus, with a median value of 6.18° (SD ± 2.88°). CONCLUSION: This study shows a significant mismatch between native and prosthetic trochlear angles. A relevant proportion of the studied knees (41.45%) fall out of the trochlear angle range of currently available implants; representing a potential source for biomechanical imbalance. While further research is warranted to fully understand the clinical implications of the present study, manufacturers may need to take these findings into account for future implant designs. LEVEL OF EVIDENCE: Level III, retrospective cohort study.

Femoral Component Rotation in Total Knee Arthroplasty Using a Tibia-First, Gap-Balancing, "Functional Alignment" Technique.

BACKGROUND: The purpose of this study was to describe the femoral component rotation in total knee arthroplasty (TKA) using a tibia-first, gap-balancing, "functional alignment" technique. METHODS: Ninety-seven patients with osteoarthritis received a TKA using computer navigation. The tibial resection was performed according to the kinematic alignment (KA) principles, while the femoral rotation was set according to the gap-balancing technique. Preoperative MRIs and intraoperative resection depth data were used to calculate the following rotational axes: the transepicondylar axis (TEA), the posterior condylar axis (PCA) and the prosthetic posterior condylar axis (rPCA). The angles between the PCA and the TEA (PCA/TEA), between the rPCA and the PCA (rPCA/PCA) and between the rPCA and the TEA (rPCA/TEA) were measured. Data regarding patellar maltracking and PROMs were collected for 24 months postoperatively. RESULTS: The mean PCA/TEA, rPCA/TEA and rPCA/PCA angles were -5.1° ± 2.1°, -4.8° ± 2.6° and -0.4° ± 1.7°, respectively (the negative values denote the internal rotation of the PCA to the TEA, rPCA to TEA and rPCA to PCA, respectively). There was no need for lateral release and no cases of patellar maltracking. CONCLUSIONS: A tibia-first, gap-balancing, "functional alignment" approach allows incorporating a gap-balancing technique with kinematic principles. Sagittal complexities in the proximal tibia (variable medial and lateral slopes) can be accounted for, as the tibial resection is completed prior to setting the femoral rotation. The prosthetic femoral rotation is internally rotated relative to the TEA, almost parallel to the PCA, similar to the femoral rotation of the KA-TKA technique. This technique did not result in patellar maltracking.

Wide variation in tibial slopes and trochlear angles in the arthritic knee: a CT evaluation of 4116 pre-operative knees.

PURPOSE: As surgeons continue to grapple with persistent issues of patient dissatisfaction post-TKA, the literature has focused on the coronal plane when considering alignment strategies but has largely ignored the sagittal and axial planes. The purpose of this retrospective observational cohort study is to evaluate variability in knee anatomy and alignment beyond the coronal plane and rationalise how this relates to existing arthroplasty alignment philosophies. METHODS: 4116 knee CTs from 360 Knee Systems© database of arthritic pre-operative TKA patients were evaluated. Standardised bony landmarks were used in each CT to determine the hip-knee angle, medial proximal tibial angle, lateral distal femoral angle, medial plateau posterior tibial slope, lateral plateau posterior tibial slope, trochlea angle (TA) to distal femoral angle (TA-DFA) and TA to posterior condylar angle (TA-PCA). Analysis was performed to determine the distributions of each measure across the cohort population. RESULTS: Both the medial and lateral PTS ranged from 5° anterior to 25° posterior. 22.6% of patients had differential PTS greater than 5°. 14.5% have greater lateral PTS (mean difference to medial PTS of 4.8° ± 5.0°), whilst 31.0% have greater medial PTS (mean difference to lateral PTS of 5.7° ± 3.2°). 14% of TA-DFAs and 5.2% of TA-PCAs vary greater than 10°. CONCLUSION: This study demonstrates a wide variation in tibial slope, differential slope between the medial and lateral tibial plateau as well as variation in the trochlear geometry. There has been an overemphasis in the literature on coronal alignment, ignoring the considerable variability present in tibial and patellofemoral morphology. Existing arthroplasty techniques are based on assumptions that may not adequately address the anatomy of morphologic outliers and could lead to dissatisfaction. LEVEL OF EVIDENCE: III-retrospective cohort study.

Comparison of intra-articular administration of adenosine, lidocaine and magnesium solution and tranexamic acid for alleviating postoperative inflammation and joint fibrosis in an experimental model of knee arthroplasty.

BACKGROUND: Dysregulated inflammatory responses are implicated in the pathogenesis of joint stiffness and arthrofibrosis following total knee arthroplasty (TKA). The purpose of this study was to compare the effects of intra-articular (IA) administration of tranexamic acid (TXA), an anti-fibrinolytic commonly used in TKA, and ALM chondroprotective solution on postoperative inflammation and joint tissue healing in a rat model of knee implant surgery. METHODS: Male Sprague-Dawley rats (n = 24) were randomly divided into TXA or ALM treatment groups. The right knee of each rat was implanted with titanium (femur) and polyethylene (tibia) implants. An IA bolus (0.1 ml) of TXA or ALM was administered after implantation and capsule closure, and before skin closure. Postoperative coagulopathy, haematology and systemic inflammatory changes were assessed. Inflammatory and fibrotic markers were assessed in joint tissue, 28 days after surgery. RESULTS: Haemostasis was comparable in animals treated with TXA or ALM after knee implant surgery. In contrast to ALM-treated animals, systemic inflammatory markers remained elevated at day 5 (IL-6, IL-12, IL-10, platelet count) and day 28 (IL-1ß, IL-10) following surgery in TXA-treated animals. At day 28 following surgery, the extension range of motion of operated knees was 1.7-fold higher for ALM-treated animals compared to the TXA group. Key inflammatory mediators (NF-κB, IL-12, IL-2), immune cell infiltration (CD68+ cells) and markers of fibrosis (α-SMA, TGF-ß) were also lower in capsular tissue of ALM-treated knees at day 28. CONCLUSION: Data suggest that IA administration of ALM is superior to TXA for reducing postoperative systemic and joint inflammation and promoting restoration of healthy joint tissue architecture in a rat model of TKA. Further studies are warranted to assess the clinical translational potential of ALM IA solution to improve patient outcomes following arthroplasty.

Intraosseous Regional Prophylactic Antibiotics Decrease the Risk of Prosthetic Joint Infection in Primary TKA: A Multicenter Study.

BACKGROUND: Recent studies have demonstrated that the administration of regional prophylactic antibiotics by intraosseous (IO) injection achieves tissue concentrations around the knee that are 10- to 15-fold higher than intravenous (IV) delivery of prophylactic antibiotics. It is currently unknown whether the use of regional prophylactic antibiotics for primary TKA would result in a lower risk of prosthetic joint infection (PJI). QUESTIONS/PURPOSES: (1) Is IO injection of prophylactic antibiotics associated with a decreased risk of early (< 12 months) deep PJI compared with traditional IV prophylactic antibiotics? (2) What other patient factors are associated with an increased risk of early PJI after TKA, and do regional prophylactic antibiotics influence these risk factors? (3) Can IO antibiotics be administered to all patients, and what complications occurred from the delivery of IO prophylactic antibiotics? METHODS: A retrospective comparative study of all primary TKAs (1909 TKAs) over a 5-year period (January 2013 to December 2017) was performed to determine the risk of early PJI. Three primary TKAs did not meet the study inclusion criteria and were excluded from the study, leaving a total of 1906 TKAs (725 IO, 1181 IV) for analysis at a minimum of 12 months after index procedure. Both cohorts exhibited similar ages, BMI, and American Society of Anesthesiologists (ASA) grades; however, a greater proportion of patients in the IO cohort were smokers (p = 0.01), while a greater proportion of patients were diabetic in the IV cohort (p = 0.006). The PJI risk between IO and IV delivery techniques was compared while adjusting for patient demographics and medical comorbidities. Complications related to IO delivery-inability to administer via IO technique, compartment syndrome, fat embolism, and red man syndrome with vancomycin use-were recorded. RESULTS: The delivery of regional prophylactic antibiotics by the IO technique resulted in a lower PJI risk than IV prophylactic antibiotics (0.1% [1 of 725] compared with 1.4% [16 of 1181]; relative risk 0.10 [95% CI 0.01 to 0.77]; p = 0.03). BMI (ß = -0.17; standard error = 0.08; p = 0.02), diabetes (ß = -1.80; standard error = 0.75; p = 0.02), and renal failure (ß = -2.37; standard error = 0.84; p = 0.01) were factors associated with of PJI, while smoking, sex, and ASA score were not contributing factors (p > 0.05). Although BMI, diabetes, and renal failure were identified as infection risk factors, the use of IO antibiotics in these patients did not result in a lower PJI risk compared with IV antibiotics (p > 0.05). IO antibiotics were able to be successfully administered to all patients in this cohort, and there were no complications related to the delivery of IO antibiotics. CONCLUSION: Surgeons should consider administering regional prophylactic antibiotics in primary TKA to reduce the risk of early PJI. Future randomized prospective clinical trials are needed to validate the efficacy of regional prophylactic antibiotics in reducing the PJI risk in primary TKA. LEVEL OF EVIDENCE: Level III, therapeutic study.

Modified Broström-Gould With Gracilis Autograft Augmentation Surgery and Accelerated Noncasted Rehabilitation in High Demand Patients With Lateral Ankle Instability.

Lateral ankle instability that has failed conservative management can be physically debilitating. Good outcomes are obtained from Broström-Gould augmented repair techniques, however there are few studies evaluating the use of a gracilis autograft augmentation coupled with an accelerated rehabilitation program in high functional demand patients. We believe that the modified Broström-Gould technique utilizing a Gracilis autograft will provide significant improvements in stability while maintaining normal ankle biomechanics in young, high demand patients. The prospective cohort study involved 19 patients (20 ankles) who underwent surgery for chronic lateral ankle instability by a single surgeon, at a single institution between October 2014 and April 2016. Patients were followed for 33.8 ± 11.7 (range 12-48) months. Patients were assessed both pre- and postoperatively for talar tilt angle radiographically and with both American Orthopaedic Foot and Ankle Society Ankle and Hindfoot scores and Karlsson-Peterson scores. A Tegner activity score was taken at the last follow-up. The mean American Orthopaedic Foot and Ankle Society score increased from 68.85 ± 10.57 to 91.56 ± 5.31 points (p < .01) and mean Karlsson-Peterson score increased from 50.9 ± 15.53 to 88.11 ± 8.64 points (p value <.01) when compared preoperatively to mean postoperative follow-up of 33.8 months. Tegner activity score was 7.05 ± 0.89 at last follow-up. The technique was found to be effective in treating chronic lateral ankle instability and in combination with an accelerated rehabilitation protocol, patients returned to their premorbid level of activity with improved stability and no significant effect on donor graft site morbidity.

Pre-operative clinical predictors for cardiology referral prior to total joint arthroplasty: the 'asymptomatic' patient.

BACKGROUND: No validated pre-operative cardiac risk stratification tool exists that is specific for total hip and total knee arthroplasty (THA and TKA, respectively). To reduce the risk of post-operative cardiac complication, surgeons need clear guidance on which patients are likely to benefit from pre-operative cardiac optimisation. This is particularly important for asymptomatic patients, where the need is harder to determine. METHODS: Primary THA and TKA performed between January 1, 2010, and December 31, 2017, were identified from a single orthopaedic practice. Over 25 risk factors were evaluated as predictors for patients requiring additional cardiac investigation beyond an ECG and echocardiogram, and for cardiac abnormality detected upon additional investigation. A multivariate logistic regression was conducted using significant predictor variables identified from inferential statistics. A series of predictive scores were constructed and weighted to identify the influence of each variable on the ability to predict the detection of cardiac abnormality pre-operatively. RESULTS: Three hundred seventy-four patients were eligible for inclusion. Increasing age (p < 0.001), history of cerebrovascular accident (p = 0.018), family history of cardiovascular disease (FHx of CVD) (p < 0.001) and decreased ejection fraction (EF) (p < 0.001) were significant predictors of additional cardiac investigation being required. Increasing age (p = 0.003), male gender (p = 0.042), FHx of CVD (p = 0.001) and a reduced EF (p < 0.001) were significantly predictive for the detection of cardiac abnormality upon additional cardiac investigation. CONCLUSIONS: Increasing age, male gender, FHx of CVD and decreased ejection fraction are important risk factors to consider for pre-operative cardiac optimisation in THA and TKA patients. These findings can be applied towards future predictive models, to determine which asymptomatic patients are likely to benefit from pre-operative cardiac referral.

Computer-Assisted Technologies in Arthroplasty: Navigating Your Way Today.

Computer-assisted technologies that are used in arthroplasty include navigation, image-derived instrumentation (IDI), and robotics. Computer-assisted navigation improves accuracy and allows for real-time assessment of component positioning and soft-tissue tension. It is not clear whether the implementation of these technologies improves the clinical outcome of surgery. High cost and time demands have prevented the global implementation of computer-assisted technologies.

Evaluation of bacteriophage as an adjunct therapy for treatment of peri-prosthetic joint infection caused by Staphylococcus aureus.

Phage therapy offers a potential alternate strategy for the treatment of peri-prosthetic joint infection (PJI), particularly where limited effective antibiotics are available. We undertook preclinical trials to investigate the therapeutic efficacy of a phage cocktail, alone and in combination with vancomycin, to reduce bacterial numbers within the infected joint using a clinically-relevant model of Staphylococcus aureus-induced PJI. Infected animals were randomised to 4 treatment groups, with treatment commencing 21-days post-surgery: bacteriophage alone, vancomycin alone, bacteriophage and vancomycin, and sham. At day 28 post-surgery, animals were euthanised for microbiological and immunological assessment of implanted joints. Treatment with phage alone or vancomycin alone, led to 5-fold and 6.2-fold reductions, respectively in bacterial load within peri-implant tissue compared to sham-treated animals. Compared to sham-treated animals, a 22.5-fold reduction in S. aureus burden was observed within joint tissue of animals that were administered phage in combination with vancomycin, corresponding with decreased swelling in the implanted knee. Microbiological data were supported by evidence of decreased inflammation within the joints of animals administered phage in combination with vancomycin, compared to sham-treated animals. Our findings provide further support for phage therapy as a tolerable and effective adjunct treatment for PJI.

Experimental model of peri-prosthetic infection of the knee caused by Staphylococcus aureus using biomaterials representative of modern TKA.

Prosthetic joint infection (PJI) following total knee arthroplasty (TKA) remains the leading cause for revision surgery, with Staphylococcus aureus the bacterium most frequently responsible. We describe a novel rat model of implant-associated S. aureus infection of the knee using orthopaedic materials relevant to modern TKA. Male Sprague-Dawley rats underwent unilateral knee implant surgery, which involved placement of a cementless, porous titanium implant into the femur, and an ultra-highly cross-linked polyethyelene (UHXLPE) implant into the proximal tibia within a mantle of gentamicin-laden bone cement. S. aureus biofilms were established on the surface of titanium implants prior to implantation into the femur of infected animals, whilst control animals received sterile implants. Compared to controls, the time taken to full weight-bear and recover pre-surgical body weight was greater in the infected group. Neutrophils and C-reactive protein levels were significantly higher in infected compared to control animals at day 5 post surgery, returning to baseline levels for the remainder of the 28-day experimental period. Blood cultures remained negative and additional plasma inflammatory markers were comparable for control and infected animals, consistent with the clinical presentation of delayed-onset PJI. S. aureus was recovered from joint tissue and implants at day 28 post surgery from all animals that received pre-seeded titanium implants, despite the use of antibiotic-laden cement. Persistent localised infection was associated with increased inflammatory responses and radiological changes in peri-implant tissue. The availability of a preclinical model that is reproducible based on the use of current TKA materials and consistent with clinical features of delayed-onset PJI will be valuable for evaluation of innovative therapeutic approaches.

Absence of cytotoxic and inflammatory effects following in vitro exposure of chondrogenically-differentiated human mesenchymal stem cells to adenosine, lidocaine and Mg2+ solution.

BACKGROUND: ALM solution, a combination of adenosine, lidocaine and Mg2+, is an emerging small volume therapy that has been shown to prevent and correct coagulopathy and surgery-related inflammation in preclinical models, though its application in orthopaedic surgery is yet to be demonstrated. The effect of ALM solution on chondrocytes is unknown. The aim of this preliminary study was to investigate the effect of ALM solution on viability and inflammatory responses of chondrogenically-differentiated human bone marrow-derived mesenchymal stem cells (chondro-MSC), in vitro. METHODS: Chondro-MSC were exposed to media only, saline (0.9% NaCl or 1.3% NaCl) only, or saline containing ALM (1 mM adenosine, 3 mM lidocaine, 2.5 mM Mg2+) or tranexamic acid (TXA, 100 mg/ml) for 1 or 4 h. Responses to ALM solutions containing higher lidocaine concentrations were also compared. Chondrocyte viability was determined using WST-8 colorimetric assays and inflammatory cytokine (TNF-α, IL-1ß, IL-8) and matrix metalloproteinases (MMP-3, MMP-12, MMP-13) concentrations using multiplex bead arrays. RESULTS: The viability of chondro-MSC was significantly greater after 1 h treatment with ALM compared to saline (96.2 ± 7.9 versus 75.6 ± 7.3%). Extension of exposure times to 4 h had no significant adverse effect on cell viability after treatment with ALM (1 h, 85.4 ± 5.6 v 4 h, 74.0 ± 15.2%). Cytotoxicity was evident following exposure to solutions containing lidocaine concentrations greater than 30 mM. There were no significant differences in viability (80 ± 5.4 v 57.3 ± 16.2%) or secretion of IL-8 (60 ± 20 v 160 ± 50 pg/ml), MMP-3 (0.95 ± 0.6 v 3.4 ± 1.6 ng/ml), and MMP-13 (4.2 ± 2.4 v 9.2 ± 4.3 ng/ml) in chondro-MSC exposed to saline, ALM or TXA. CONCLUSIONS: Short-term, in vitro exposure to clinically-relevant concentrations of ALM solution had no adverse inflammatory or chondrotoxic effects on human chondro-MSC, with responses comparable to saline and TXA. These findings provide support for continued evaluation of ALM solution as a possible therapeutic to improve outcomes following orthopaedic procedures.

The CNS theory of osteoarthritis: Opportunities beyond the joint.

Osteoarthritis (OA) is a leading cause of global disability that affects more than half of the population over 65. It is not a single disease but a progressive, inflammatory- and immune-altering multi-disease that affects the whole joint. OA has many risk factors including age, obesity, gender, lifestyle, joint morphology, metabolic dysfunction and genetic disposition. A major stumbling block in treating clinical OA has been the inability to detect its early onset and disease progression. This gap in understanding may arise from our failure to recognize that the OA patient exhibits a vulnerability to dysregulation of central feedback circuits that control sympathetic tone, inflammation, circadian rhythms (central and peripheral clocks), gut microbiome, metabolic redox and whole joint pathology. Early detection of OA and slowing its progression may come from discoveries outside the joint targeting these potentially modifiable upstream targets. We argue that future treatments may benefit from moving from a knee-centric viewpoint to a more systems-based, whole-body approach. The challenge, however, will be to better characterize these key circuits and apply this knowledge to develop new therapies and interventions.

Risk factors associated with cardiac complication after total joint arthroplasty of the hip and knee: a systematic review.

BACKGROUND: Cardiac complication represents a major cause of morbidity and mortality after total joint arthroplasty, thus necessitating investigation into the associated risks in total hip arthroplasty and total knee arthroplasty. There remains a lack of clarity for many risk factors in the current literature. The aim of this systematic review is to assess the most recent published literature and identify the risk factors associated with cardiac complication in total hip arthroplasty and total knee arthroplasty. METHODS: Scopus, PubMed, CINHAL, and Cochrane were searched to identify studies published since 2008 reporting on risk factors associated with cardiac complication in elective primary in total hip arthroplasty and total knee arthroplasty in patients ≥18 years old with osteoarthritis. Reported odds ratios, hazard ratios, and relative risk were the principal summary measures collected. The included studies were too heterogeneous to enable meta-analysis. RESULTS: Fifteen studies were included in this systematic review. Increasing age and history of cardiac disease were found by most studies to be positively associated with risk of cardiac complication. There was no strong association found between obesity and cardiac complication. The evidence for other risk factors was less clear in the examined literature, although there is suggestive evidence for male gender and cerebrovascular disease increasing risk. CONCLUSIONS: Increasing age and history of cardiac disease increases the risk of cardiac complication after total hip arthroplasty and total knee arthroplasty. Other risk factors commonly attributed to increased risk in non-cardiac surgery including hypertension and obesity require further evaluation in arthroplasty. SYSTEMATIC REVIEW REGISTRATION: A detailed protocol was published in the PROSPERO database (registration number CRD42018095887 ) for this systematic review.

Evaluation of Bacteriophage Anti-Biofilm Activity for Potential Control of Orthopedic Implant-Related Infections Caused by Staphylococcus aureus.

BACKGROUND: Despite significant advancements in surgical protocols and biomaterials for orthopedics, peri-prosthetic joint infection (PJI) remains a leading cause of implant failure. Staphylococcus aureus nasal colonization is an established risk factor for PJI, with methicillin-sensitive S. aureus a leading cause of orthopedic implant-related infections. The purpose of these in vitro studies was to investigate the antibacterial activity of a tailored bacteriophage cocktail against planktonic and biofilm-associated S. aureus. METHODS: The S. aureus strains (n = 30) were screened for their susceptibility to a library of S. aureus-specific bacteriophage (n = 31). Five bacteriophage preparations that demonstrated bactericidal activity against >90% of S. aureus strains tested were combined as a StaPhage cocktail and assessed for their antibacterial activity toward planktonic and biofilm-associated S. aureus, with biofilms established on three-dimensional-printed porous titanium scaffolds. RESULTS: StaPhage treatment immediately after bacterial inoculation inhibited growth of S. aureus by >98% in eight hour cultures when multiplicity of infection of phages to bacteria was greater than 1:1 (p < 0.01). Viable bacterial numbers within biofilms on titanium surfaces were significantly reduced (6.8 log10 to 6.2 log10 colony forming units [CFU]; p < 0.01) after exposure to the StaPhage cocktail, in vitro. No significant reduction was observed in biofilms exposed to 100 times the minimal inhibitory concentration of cefazolin (log10 6.81 CFU). CONCLUSIONS: Combined, these data demonstrate the in vitro efficacy of S. aureus-specific bacteriophage cocktails against S. aureus growing on porous titanium and warrant further in vivo studies in a clinically relevant animal model to evaluate the potential application of bacteriophage in the management of PJI caused by S. aureus.

Early results of medial opening wedge high tibial osteotomy using an intraosseous implant with accelerated rehabilitation.

BACKGROUND: Accelerated rehabilitation protocols for medial opening wedge high tibial osteotomy (MOW HTO) using intraosseous implants have not previously been described. The present study provides early clinical and radiological outcomes of MOW HTO using a polyetheretherketone (PEEK) intraosseous system, in combination with an early weight-bearing protocol. METHODS: Twenty consecutive knees (17 patients) underwent navigated MOW HTO using a PEEK implant with accelerated rehabilitation. Time to union and maintenance of correction were assessed radiographically for 12 months post-operative. Patient outcomes were monitored for a mean follow-up of 38 months (range 23-42) using standardised instruments (WOMAC, IKDC and Lysholm scores). RESULTS: All knees were corrected to valgus. The mean time to unassisted weight-bearing was 55 days (SD 24, range 21-106). Bone union occurred in 95% of knees by 6 months, with correction maintained for 15 knees at 12 months post-operative. Knees for which correction was lost within 1 year of surgery had significantly greater preoperative varus alignment. Implant survivorship was 95% and 80% at 12 and 38 months post-operative, respectively. Significant improvements in patient-reported satisfaction, knee function and return to daily activities from preoperative to 38 months post-operative were reported (WOMAC 36 v 0; IKDC 35.6 v 96; Lysholm 44.5 v 100). CONCLUSIONS: Accelerated rehabilitation following MOW HTO with an intraosseous PEEK implant did not delay bone union, with significantly improved functional outcomes within 3 months post-operative. Early findings suggest that this approach may be suitable for a defined patient subset, with consideration for the extent of preoperative genu varum.

Use of regional administration of prophylactic antibiotics in total knee arthroplasty.

Prosthetic joint infection after total knee arthroplasty is an infrequent, yet serious complication. Antimicrobial prophylaxis plays an important role in reducing the rate of surgical site infections. To be effective as an antimicrobial prophylaxis, the serum, tissue and bone concentrations of the antibiotic must be greater than the target organism's minimum inhibitory concentration. As antibiotic resistance increases current intravenous prophylactic dosing has been shown to be subtherapeutic for some patients. Intravenous regional administration and intraosseous regional administration of prophylactic antibiotics are novel methods used to increase the antibiotic tissue concentrations, which may enhance the efficacy of prophylactic antibiotics in total knee arthroplasty. Currently, literature has shown both intravenous regional administration and intraosseous regional administration to be safe and effective techniques. However, there is no clinical evidence to show that it results in a reduction of prosthetic joint infection rates. This study summarizes the current knowledge base on the use of regional administration of prophylactic antibiotics in total knee arthroplasty.

Tranexamic acid is associated with selective increase in inflammatory markers following total knee arthroplasty (TKA): a pilot study.

BACKGROUND: Tranexamic acid (TXA) is commonly used in orthopedic surgery to reduce excessive bleeding and transfusion requirements. Our aim was to examine if TXA was required in all osteoarthritis patients undergoing TKA surgery, and its possible effects on systemic inflammation and coagulation properties. METHODS: Twenty-three patients (Oxford Score 22-29) were recruited consecutively; 12 patients received TXA before (IV, 1.2 g/90 kg) and immediately after surgery (intra-articular, 1.4 g/90 kg). Inflammatory mediators and ROTEM parameters were measured in blood at baseline, after the first bone-cut, immediately after surgery, and postoperative days 1 and 2. RESULTS: After the bone cut and surgery, TXA significantly increased MCP-1, TNF-α, IL-1ß and IL-6 levels compared to non-TXA patients, which was further amplified postoperatively. During surgery, TXA significantly prolonged EXTEM clot times, indicating a thrombin-slowing effect, despite little or no change in clot amplitude or fibrinogen. TXA was associated with three- to fivefold increases in FIBTEM maximum lysis (ML), a finding counter to TXA's antifibrinolytic effect. Maximum lysis for extrinsic and intrinsic pathways was < 8%, indicating little or no hyperfibrinolysis. No significant differences were found in postoperative hemoglobin between the two groups. CONCLUSIONS: TXA was associated with increased systemic inflammation during surgery compared to non-TXA patients, with further amplification on postoperative days 1 and 2. On the basis of little or no change in viscoelastic clot strength, fibrinogen or clot lysis, there appeared to be no clinical justification for TXA in our group of patients. Larger prospective, randomized trials are required to investigate a possible proinflammatory effect in TKA patients.