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Douglas DR Naudie,1,2 Silvio Ndoja,1 Thomas J Wood,3 Lyndsay E Somerville,1 James L Howard,1,2 Richard W McCalden,1,2 Steven J MacDonald,1,2 Brent A Lanting1,2 1Division of Orthopaedic Surgery, Department of Surgery, London Health Sciences, London, Ontario, Canada; 2Bone and Joint Institute, Western University, London, Ontario, Canada; 3Division of Orthopaedic Surgery, Department of Surgery, Hamilton Health Sciences, McMaster University, Hamilton, Ontario, CanadaCorrespondence: Douglas DR NaudieDivision of Orthopaedic Surgery, Department of Surgery, Western University, Schulich School of Medicine, London Health Sciences Centre, University Campus, A9-028,339 Windermere Road, London, Ontario N6A 5A5, CanadaEmail Douglas.Naudie@lhsc.on.caIntroduction: Corrosion at the head–neck interface of modular components in total hip arthroplasty (THA) has been reported as a cause of failure of modern total hip replacement implants. While this method of failure has been well described, it remains poorly understood. The purpose of this study is to review the three most commonly used uncemented femoral stems at our institution over the last fifteen years and to correlate any established risk factors with rates of revision, particularly corrosion.Methods: We reviewed 2095 patients from March 2000 to September 2015 who underwent total hip arthroplasty with one of three uncemented femoral stem designs. All stems were made of a Ti6Al4V alloy with a 12/14 taper design. We included only those stems coupled with a CoCr head and a highly crosslinked polyethylene liner. We evaluated age, gender, body mass index (BMI), femoral head size, head length, neck angle and offset and correlated these to the incidence of all cause revision, as well as revision excluding infection.Results: There were no recognized corrosion-related revisions identified. There was no association between age, BMI, gender, head length, neck angle and offset to all cause revision or revision with infection excluded (p> 0.05). Femoral head size less than 32mm was associated with higher all cause revision rates (OR 4.60 (95% CI 1.8, 11.8)) and when excluding infection as a reason for revision (OR 4.94 (95% CI 1.7, 14.41)).Conclusion: Over the last fifteen years, we have not identified any cases of corrosion with the three most commonly used femoral stems used at out institution. While we acknowledge that no femoral stem is immune to corrosion, certain femoral stem designs may be uniquely resistant to this mode of failure.Level of Evidence: III.Keywords: corrosion, revision, total hip arthroplasty, femoral stems

Mohammad M Alzahrani,1 Thomas J Wood,2 Lyndsay E Somerville,3 Steven J MacDonald,3 James L Howard,3 Edward M Vasarhelyi,3 Brent A Lanting3 1Department of Orthopaedic Surgery, College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia; 2Division of Orthopaedic Surgery, Department of Surgery, Hamilton Health Sciences, McMaster University, Hamilton, ON, Canada; 3Division of Orthopaedic Surgery, Department of Surgery, London Health Sciences Centre University Campus, University of Western Ontario, London, Ontario N6A 5A5, CanadaCorrespondence: Mohammad M AlzahraniDepartment of Orthopaedic Surgery, College of Medicine, Imam Abdulrahman Bin Faisal University, 2835 King Faisal Road, Dammam 34212, Saudi ArabiaEmail mmalzahrani@iau.edu.saIntroduction: Outcomes and longevity of total knee arthroplasty (TKA) depend mainly on restoring knee function, through precise bony resection and appropriate soft tissue balancing. The current literature lacks evidence regarding the degree of radiographic change after intra-operative knee balancing. The purpose of our study was to assess the degree of change in coronal lower extremity alignment by comparing pre-operative to post-operative full-length radiographs (FLR) after quantifying the degree of intra-operative knee balancing and correlate patient-reported outcomes to the extent of balancing required.Patients and Methods: One hundred and fifty-four patients undergoing primary TKA for varus knee osteoarthritis were included in the study. The performed soft tissue releases and bony adjustments to obtain a balanced TKA intra-operatively were prospectively documented and were grouped into minimal, moderate and extensive release groups. Hip-knee-ankle angle (HKA), anatomical femoral-tibial angle (FTA), condylar hip angle (CH), medial proximal tibial angle (MPTA) and condylar plateau angle (CPA) were measured on full-length radiographs both pre-operatively and post-operatively. Frequencies of the soft tissue releases and bony resections in addition to descriptive statistics of the measured angles on the radiographs were recorded. In addition, patient-reported outcome scores (PROMs) were compared between the grouped patients.Results: Of those that were included in the study, 66 knees (42.9%) required minimal release to adequately balance the knee, while 70 (45.5%) required moderate release and 18 (11.7%) required extensive release. No statistically significant differences were found in change of alignment between the groups for all the measured angles. In addition, no difference in PROMs was seen between the groups both pre- and post-operatively.Conclusion: Although we found no association between post-operative coronal alignment of a TKA and the degree of soft tissue release and bony resection, this likely represents the fact that a balanced TKA is dynamic and not dependent on change of single radiographic parameters. Patient-reported outcomes were not impacted by the extent of releases.Keywords: knee arthroplasty, soft tissue, balancing, alignment, outcomes

Background: TKA and unicompartmental knee arthroplasty (UKA) are both utilized to treat unicompartmental knee arthrosis. While some surgeons assume UKA provides better function than TKA, this assumption is based on greater final outcome scores rather than on change in scores and many patients with UKA have higher preoperative scores.Questions/purposes: We therefore asked whether TKA would demonstrate (1) better change in clinical outcome scores from preoperative to postoperative states and (2) better survivorship than UKA.Methods: We evaluated 4087 patients with 5606 TKAs and 179 patients with 279 UKAs performed between 1978 and 2009. Patients with TKA were older and heavier than patients with UKA (mean age, 68 versus 66 years; mean BMI, 32 versus 29). We compared preoperative, latest postoperative, and change in Knee Society Clinical Rating System (KSCRS), SF-12, and WOMAC scores. Minimum followup was 2 years (UKA: mean, 7 years; range, 2.0-23 years; TKA: mean, 6.5 years; range, 2.0-33 years). Preoperative outcome measure scores (WOMAC, SF-12, KSCRS) were higher in the UKA group.Results: Patients with UKA had higher postoperative KSCRS and SF-12 mental scores. Changes in score for all WOMAC domains were similar between groups. Total KSCRS changes in score were similar between groups, although patients with TKA had higher knee scores (49 versus 43) but lower function scores than UKA (21 versus 26). Cumulative revision rate was higher for UKA than for TKA (13% versus 7%). Kaplan-Meier survivorship at 5 and 10 years was 95% and 90%, respectively, for UKA and 98% and 95%, respectively, for TKA.Conclusions: While patients with UKA had higher pre- and postoperative scores than patients with TKA, the changes in scores were similar in both groups and survival appeared higher in patients with TKA. [ABSTRACT FROM AUTHOR]

Despite recent advances in understanding dyslexia as a neurological condition, anumber of academics in both the United Kingdom and United States have dismissed the validity of this impairment. The key thinking behind this approach is twofold. Firstly, individuals labelled as having dyslexia cannot be separated from individuals with general reading difficulties. Secondly, educational 'treatment' of dyslexia is consistent with educational support for children labelled as having general reading difficulties. Rather than expand on a psycho-cognitive approach, this article endeavours to reflect on individual subjectivities. This is to analyse the social aspects of dyslexia and its symptoms. By discussing the life stories of people diagnosed with dyslexia, the article confronts certain stereotypes associated with this syndrome. In doing so, the study concludes by developing a meaningful response to the label of learning difficulties. [ABSTRACT FROM AUTHOR]

Unlabelled: There are two broad-based categories of cementless femoral component designs: proximally porous-coated and fully porous-coated. While both have been widely used, there remains debate regarding differences in clinical outcome scores, relative incidence of thigh pain, and development of stress shielding. We investigated these variables in a multicenter prospective randomized blinded clinical trial of 388 patients from three centers: 198 patients had a proximally porous-coated tapered cementless femoral component and 190 patients had a fully porous-coated cementless femoral component. A minimum followup of 2 years (mean, 6.7 years; range, 2.0-8.65 years) was available in 367 of the 388 patients (95%). We observed no differences in age at surgery, body mass index, or preoperative clinical outcome scores (WOMAC, SF-12, Harris hip score, UCLA activity, thigh pain) with the two groups. We determined serial bone density changes in a subcohort of 72 patients from two of the three centers. The postoperative clinical outcome scores were similar at all followup intervals, and we observed no differences in the incidence of thigh pain at any time. Bone density reduction in Gruen Zone 7 was greater with the fully coated stem than the proximally coated stem (24% versus 15% reduction, respectively). Both fully and proximally coated stems performed well, with no clinical differences at 2 years' followup, except in bone mineral density evaluations.Level Of Evidence: Level I, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence. [ABSTRACT FROM AUTHOR]

Unlabelled: The range of motion after TKA depends on many patient, surgical technique, and implant factors. Recently, high-flexion designs have been introduced as a means of ensuring or gaining flexion after TKA. We therefore evaluated factors affecting postoperative flexion to determine whether implant design influences longterm flexion. We prospectively collected data on patients receiving a primary Genesis II total knee replacement with a minimum of 1-year followup (mean, 5.4 years; range, 1-13 years). We recorded pre- and postoperative outcome measures, patient demographics, and implant design (cruciate retaining [CR, n = 160], posterior stabilized [PS, n = 1177], high-flex posterior stabilized [HF-PS, n = 197]). Backward stepwise linear regression modeling identified the following factors affecting postoperative flexion: preoperative flexion, gender, body mass index, and implant design. Independent of gender, body mass index, and preoperative flexion, patients who received a HF-PS and PS design implant had a mean of 8 degrees and 5 degrees more flexion, respectively, than those who received a CR implant. Patients with low flexion preoperatively (<100 degrees) were more likely to gain flexion, whereas those with high flexion preoperatively (>120 degrees) were most likely to maintain or lose flexion postoperatively. Controlling for implant design, patients with high flexion preoperatively (>120 degrees) were more likely to gain flexion with the HF-PS design implant (HF-PS = 32.0%; PS = 15.1%; CR = 4.5%).Level Of Evidence: Level II, prognostic study. See Guidelines for Authors for a complete description of levels of evidence. [ABSTRACT FROM AUTHOR]

Unlabelled: The inset biconvex patella component is an alternative form of patella resurfacing in knee arthroplasty. We retrospectively reviewed 433 patients in whom 521 patella prostheses were implanted before April 1997 to determine survivorship, factors associated with failure of the implant, incidence of anterior knee pain, and factors that may be associated with the latter. We had clinical results for 204 surviving patients (242 knees) without failure of their implants with a minimum 10-year followup (mean, 11.4 years; range, 10-17 years). For the remaining 229 patients we used chart or radiographic review to determine if failure of their implant or other complications had occurred. At latest followup, 14 patella components had been revised for aseptic reasons or were radiographically loose. The 10-year Kaplan-Meier survivorship for the entire cohort for aseptic failure was 97.0%. Aseptic failure of the patella component was associated with the presence of osteonecrosis and the absence of a superior rim of bone radiographically. The incidence of anterior knee pain in surviving patients without failure of their implants was 7.8%. No factor examined was associated with anterior knee pain. Survivorship and clinical and radiographic results are equivalent, but not clearly superior, to those reported for other forms of patella resurfacing.Level Of Evidence: Level IV, therapeutic study. [ABSTRACT FROM AUTHOR]

Background: Highly cross-linked polyethylene was introduced for clinical use in total hip arthroplasty with the expectation that it would exhibit less wear when compared with conventional polyethylene. The purpose of this study was to report the clinical and radiographic results, after a minimum of five years of follow-up, of a randomized, blinded, controlled trial comparing a conventional polyethylene with a first-generation highly cross-linked polyethylene.Methods: One hundred patients were enrolled in a prospective, randomized controlled study comparing highly cross-linked and conventional polyethylene acetabular liners in total hip arthroplasty. Fifty patients were in each group. At the time of follow-up, clinical outcomes were assessed and steady-state femoral head penetration rates (after bedding-in) for each patient were calculated with use of a validated radiographic technique. In addition, a statistical comparison of polyethylene wear between groups was performed with use of generalized estimating equations.Results: At a mean of 6.8 years postoperatively, there were no differences between the two polyethylene groups with regard to the Harris hip score, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), or Short Form-12 (SF-12) score. The mean femoral head penetration rate in the first through fifth years was found to be significantly lower in the group treated with the highly cross-linked polyethylene (0.003 mm/yr [95% confidence interval, +/-0.027]) than it was in the group treated with conventional polyethylene (0.051 mm/yr [95% confidence interval, +/-0.022]) (p=0.006). Men treated with a conventional polyethylene liner had a significantly higher (pConclusions: At a minimum of five years postoperatively, the steady-state femoral head penetration rate associated with this first-generation highly cross-linked polyethylene liner was significantly lower than that associated with a conventional polyethylene liner. Long-term follow-up is required to demonstrate the clinical benefit of this new material. [ABSTRACT FROM AUTHOR]

The worldwide number of primary total hip replacements has increased over the last decade, and as the number of primary total hip arthroplasties (THAs) increases each year, the number of revision THAs can also be expected to increase. Revision THAs often lead to suboptimal results, more complications and high costs. The rapid growth of new surgical techniques and new hip implants warrants a continuous and objective monitoring of the results to lower revision rates and improve outcomes. From an international standpoint, the revision burden is one of the possible key figures that allow crude comparisons between different countries and health systems. Evidence based information and revision rates can be derived from national joint registry data. In countries without registries, data can be collected from large data sets used for billing, national hospital discharge surveys and quality surveys. In addition single- and multicentre data regarding revision THA in combination with randomised control trials (RCTs) can be used. However, certain strengths and weaknesses apply to non-registry data sources which will be discussed. It was shown that the overall revision burden which is as high as 17.5% in some countries, could be improved in countries with national joint registries. One way to lower revision rates in the future is to use evidence-based primary implants. Registry data have the power to identify such implants, surgical techniques and processes. Thus it can guide surgeons in an evidence-based fashion to the benefit of patient outcome. [ABSTRACT FROM AUTHOR]

Background: Postoperative analgesia with the use of parenteral opioids or epidural analgesia can be associated with troublesome side effects. Good perioperative analgesia facilitates rehabilitation, improves patient satisfaction, and may reduce the hospital stay. We investigated the analgesic effect of locally injected drugs around a total knee prosthesis.Methods: Sixty-four patients undergoing total knee arthroplasty were randomized either to receive a periarticular intraoperative injection containing ropivacaine, ketorolac, epimorphine, and epinephrine or to receive no injection. The perioperative analgesic regimen was standardized. All patients in both groups received patient-controlled analgesia for twenty-four hours after the surgery, and this was followed by standard analgesia. Visual analog scores for pain, during activity and at rest, and for patient satisfaction were recorded preoperatively and postoperatively and at the six-week follow-up examination. The consumption of patient-controlled analgesia at specific postoperative time-points and the overall analgesic requirement were measured.Results: The patients who had received the injection used significantly less patient-controlled analgesia at six hours, at twelve hours, and over the first twenty-four hours after the surgery. In addition, they had higher visual analog scores for patient satisfaction and lower visual analog scores for pain during activity in the post-anesthetic-care unit and four hours after the operation. No cardiac or central nervous system toxicity was observed.Conclusions: Intraoperative periarticular injection with multimodal drugs can significantly reduce the requirements for patient-controlled analgesia and improve patient satisfaction, with no apparent risks, following total knee arthroplasty. [ABSTRACT FROM AUTHOR]

BACKGROUND: The demand for total hip and total knee arthroplasties is increasing as are the waiting times for these procedures. Because of the differences between rural and urban areas in terms of the provision of arthroplasty services and between the 2 patient groups, patient perspectives of waiting times may also be different. METHODS: To compare waiting times for initial orthopedic consultation and total hip and knee arthroplasties in rural Ontario (Stratford) and in urban Ontario (London), and to compare patient perspectives of these waiting times, we mailed a survey to all 260 patients who underwent total hip or total knee arthroplasty between June 1, 2000, and June 1, 2001. The survey asked for the length of wait for consultation and for surgery, acceptability of waiting time for surgery, the effect of waiting on health and what an acceptable waiting time would be. Of the 260 surveys mailed 202 (78%) were returned. We reviewed the charts of the respondents to determine the actual waiting times. RESULTS: The actual waiting times (mean [and standard deviation]) for initial consultation were significantly (p < 0.001) shorter in the rural (RUR) group (1.10 [0.53] mo) than the urban (URB) group (3.40 [1.34] mo). There was no significant difference in waiting times for surgery between RUR (8.45 [3.32] mo) and URB (9.32 [3.61] mo) groups. Surgical waiting times for both groups showed that 56% of all the patients had to wait longer than 9 months from the date surgery was recommended. Perceived waiting times for consultation were found to be 56.9% longer (p < 0.001) than the actual waiting times, but there was no significant difference between perceived and actual waiting times for surgery (p = 0.40). Fifty percent of the patients stated they were unhappy with the wait for surgery or found the wait unacceptable (56% of URB and 44% of RUR patients). There was no significant difference between RUR and URB in patients' acceptance of their wait for surgery (p = 0.09), but URB patients believed their wait for surgery made a greater contribution to health deterioration (p = 0.003). Thirty-eight percent of RUR and 54% of URB patients believed their surgical wait contributed to 'a lot' or a 'moderate' amount of deterioration in their health. CONCLUSIONS: Waiting times for hip or knee replacement surgery have increased to the point at which over 50% of surgical patients in 2000-2001 in RUR and URB orthopedic practices had waited longer than 9 months for surgery. In comparing these practices, there was a significantly longer wait in urban than rural practices for the initial consultation but no significant difference in waiting times for surgery. [ABSTRACT FROM AUTHOR]

Objective: To identify the presence and distribution of histopathological features of synovial inflammation and tissue damage, and to test their associations with ultrasound (US) imaging measures of synovitis and patient-reported measures of pain in knee osteoarthritis (OA)., Design: In the cross-sectional study of 122 patients undergoing surgery for painful late-stage (Kellgren-Lawrence Grade 3 or 4) knee OA, we compared US measures of synovitis (n = 118) and pain (Knee Injury and Osteoarthritis Outcome Score) to histopathological measures of inflammation vs. synovial tissue damage in synovial tissue biopsies. Associations of histopathological features with US measures of inflammation or pain were assessed using linear or logistic regression while controlling for covariates., Results: Histopathological features of inflammation were associated with higher odds of moderate/severe US synovitis (odds ratio [OR] = 1.34 [95%CI 1.04, 1.74), whereas features of synovial tissue damage were associated with lower odds of moderate/severe US synovitis (OR = 0.77 [95%CI 0.57, 1.03]). Worse histopathological scores for synovial tissue damage were associated with more pain (-1.47 [95%CI -2.88, -0.05]), even while adjusting for synovial inflammation (-1.61 [95%CI -3.12, -0.10])., Conclusions: Synovial tissue damage is associated with pain in late-stage knee OA, independent from inflammation and radiographic damage. These novel findings suggest that preventing synovial tissue damage may be an important goal of disease-modifying OA therapy., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: We quantified the effect of acute exposure to a high dosage of inorganic mercury on gene expression in Drosophila melanogaster using RNA-sequencing of whole adult females., Results: We found 119 genes with higher gene expression following treatment (including all 5 Drosophila metallothionine genes and a number of heat shock protein genes), and 31 with lower expression (several of which are involved in egg formation). Our results highlight biological processes and genetic pathways impacted by exposure to this toxic metal, and provide motivation for future studies to understand the genetic basis of response to mercury., (© 2024. The Author(s).)

Background: Modular titanium fluted tapered (TFT) stems have demonstrated excellent clinical success for femoral revision total hip arthroplasty (THA) surgery. This study reports the short-term outcomes of a novel modern monoblock TFT stem used for revision and complex primary THA with a minimum of 2 years of follow-up., Methods: We identified 126 patients who received a single monoblock TFT stem: 26 patients for complex THA (failed fracture fixation) and 100 patients for revision THA. The reasons for revision THA included 40 for previous periprosthetic joint infection, 42 for aseptic loosening, 9 for trunnionosis, and 9 for periprosthetic fractures. The Paprosky grading for femoral bone loss at the time of surgery and the measured subsidence of femoral stems at 3-month follow-up were determined. We evaluated the number and indications for reoperations., Results: The mean time from surgery was 3.9 years (range, 2.0 to 6.9). A paired t-test analysis showed significant improvement from preoperative versus postoperative clinical outcome scores (P < .001) for Harris Hip Score (38.76 ± 15.24 versus 83.42 ± 15.38), Western Ontario and McMaster Universities Arthritis Index (45.6 ± 19.0 versus 69.9 ± 21.3), Veterans RAND 12 Item Health Survey Physical component (31.7 ± 8.1 versus 37.8 ± 11.3), and Veterans RAND 12 Item Health Survey Mental component (48.2 ± 12.2 versus 51.6 ± 12.5). The Paprosky grading for femoral bone loss was Grade 1 (3.9%), Grade 2 (35.7%), Grade 3A (47.6%), Grade 3B (11.1%), and Grade 4 (1.6%) cases. There were 18 reoperations (14.7%), with 13 for periprosthetic joint infection (7 treated with implant retention and 6 treated with a 2-stage revision), 4 for instability, and 1 for acetabular aseptic loosening. There were no aseptic failures of the stem., Conclusions: This novel modern monoblock TFT stem provided reliable femoral fixation and has increasingly supplanted the use of modular TFT stems for complex primary and revision surgery in our institution., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: The aim of the study was to analyze the Canadian Cardiovascular Society (CCS) guidelines for routine postoperative troponin testing after elective total hip arthroplasty (THA) to reduce the mortality rate resulting from myocardial injury. The purpose of this study was to assess the prognostic relevance of implementing these guidelines to minimize cardiac events in patients undergoing elective THA., Methods: Patients who underwent THA surgery in 2020 were included in the study. The inclusion criteria were elective THA patients aged ≥45 years, while emergency, revision, and simultaneous bilateral THA surgeries were excluded. The patients were categorized into 4 groups based on the CCS guidelines., Results: The study included 669 patients who had an average age of 67 years. There were 43 patients (6.4%), who experienced a rise in troponin levels ≥30 ng/L and developed myocardial injury after noncardiac surgery. Among these patients, 8 developed cardiac complications, and one experienced a serious cardiac event that resulted in death. Notably, there was a significant increase in the length of hospital stay for patients who received the postoperative screening protocol., Conclusions: The implementation of the CCS guidelines for routine postoperative troponin testing in elective THA surgery did not significantly decrease the rate of cardiac events or mortality., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Periprosthetic joint infection (PJI) continues to be one of the leading causes of failure following total hip arthroplasty (THA). The objectives of the study were to (1) determine the minimum 2-year infection-free survivorship of 2-stage revision THA, (2) determine the causative organisms for repeat 2-stage revision THA, and (3) characterize the results of failed 2-stage revisions and evaluate patient-reported outcome measures (PROMs)., Methods: A retrospective chart review was completed for patients who underwent 2-stage revision THA for PJI. Prospective data were collected on each patient, including demographics, causative organisms, complications, and type of reoperation. The PROMs, including Harris Hip Score, 12-item Short-Form Health Survey, and Western Ontario and McMaster Universities Osteoarthritis Index scores were obtained prior to 2-stage revision THA surgery and annually as part of standard clinical and radiographic follow-up., Results: A total of 328 patients who underwent a 2-stage revision THA for a PJI were included in the study (mean age 67 years [range, 28 to 90], mean body mass index of 30.6 [range, 15 to 57]). The overall infection-free survivorship for 2-stage revision THA was 73.8% at a minimum of 2 years (range, 2 to 20). Overall, 194 (59.1%) patients who had successful infection eradication underwent a 2-revision THA only. The most common single organisms infected were Staphylococcus aureus (12.5%) and Staphylococcus epidermidis (11%). Higher reoperation rates were found in cases with methicillin-resistant Staphylococcus aureus and polymicrobial infections. All PROMs showed statistical improvement from preoperatively to the latest follow-up appointment., Conclusions: Two-stage revision THA is associated with a good success rate in the treatment of PJIs at mid-term to long-term follow-up. Polymicrobial and methicillin-resistant Staphylococcus aureus infections are poor prognostic factors, making the eradication of infection more difficult. The management of PJIs continues to be one of the most important orthopaedic challenges to treat., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Routine patellar resurfacing during primary total knee arthroplasty (TKA) remains controversial. To our knowledge, there are no studies reporting the long-term performance of a cemented biconvex all-polyethylene inlay component implanted at the time of primary TKA. The purpose of this study was to examine the 15-year survivorship and long-term clinical outcomes of this biconvex inlay patella used at our institution., Methods: We retrospectively reviewed our prospectively collected institutional database and identified 2,530 patients who underwent cemented TKA with a single prosthetic design (from 1996 to 2007) where the patella was resurfaced using this cemented biconvex inlay patella. The mean age at surgery was 68 years (range, 29 to 93). The mean body mass index was 33.0 (range, 16.4 to 76.3), with 61.9% women. At the time of analysis, the mean time from surgery was 20.4 years (range, 15 to 26). We used Kaplan-Meier analysis to calculate survivorship at 15 years. We analyzed clinical outcomes using 3 patient-reported outcome measures collected prospectively., Results: The 15-year survivorship with revision surgery for all causes as the end point was 97.1% (95% confidence interval 96.1 to 98.1%). The 15-year survivorship with revision surgery for a patella-related complication as the end point was 99.7% (95% confidence interval 99.4 to 1.0). At the final follow-up, patients showed significant improvement in scores for the Knee Society Clinical Rating System (P < .001), Western Ontario and McMaster University Osteoarthritis Index (P < .001), and Veterans Rand 12-Item Health Survey physical component (P < .001)., Conclusions: Routine patellar resurfacing using a biconvex inlay patellar component has excellent survivorship and a low rate of complications at 15 years post-TKA., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: The primary aim of this study was to evaluate secondary patellar resurfacing (SPR) indications and rates in a single-surgeon series utilizing a modern TKA design and additionally, to review the functional outcomes of patients after undergoing SPR., Methods: A retrospective review of a prospectively collected institutional database was performed. All patients undergoing primary TKA by a single surgeon between 2013 and 2021 were included. During this time, the senior surgeon resurfaced the patella selectively. Patients were divided into the primary resurfaced (PR) and the primary unresurfaced (UR). All patients undergoing SPR in the UR group were identified, their radiographs reviewed, and their clinical outcomes assessed. During the study period, 1,511 TKAs were performed, with 73.1% (1,105 TKAs) being unresurfaced., Results: The all-cause revision rate was 1.2% in the PR group and 3.6% in the UR group. The rate of SPR in the UR group was 2.0% (22 of 1,105 TKAs). No patient in the PR group underwent revision surgery for a patellar complication. The mean age at primary TKA for those undergoing SPR was 65 years (range, 50 to 78). The average time for SPR from primary TKA was 3.4 years (range, 1.1 to 8.8). Postoperative radiographic progression of patellar erosion, in combination with new onset anterior knee pain, was the indication for SPR in 14 of the 22 (63.7%) SPR cases. After SPR, the Western Ontario and McMaster University Osteoarthritis Index score (P < .001) and Knee Society Score (P < .001) improved from pre-SPR., Conclusions: Secondary patellar resurfacing (SPR) was the most common (55%) reason for revision surgery after primary UR TKA in this series. An SPR improved clinical outcomes in symptomatic patients. Surgeons should consider patellar resurfacing for all patients undergoing primary TKA to reduce the burden of revision surgery post-TKA. Additionally, the paradigm that late SPR does not improve clinical outcomes needs to be revisited., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Production of metal debris from implant wear and corrosion processes is now a well understood occurrence following hip arthroplasty. Evidence has shown that metal ions can enter the bloodstream and travel to distant organs including the brain, and in extreme cases, can induce sensorial and neurological diseases. Our objective was tosimultaneously analyze brain anatomy and physiology in patients with long-term and well-functioning implants. Included were subjects who had received total hip or hip resurfacing arthroplastywith an implantation time of a minimum of 7 years (n = 28) and age- and sex-matched controls (n = 32). Blood samples were obtained to measure ion concentrations of cobalt and chromium, and the Montreal Cognitive Assessment was performed. 3T MRI brain scans were completed with an MPRAGE sequence for ROI segmentation and multiecho gradient echo sequences to generate QSM and R2* maps. Mean QSM and R2* values were recorded for five deep brain and four middle and cortical brain structures on both hemispheres: pallidum, putamen, caudate, amygdala, hippocampus, anterior cingulate, inferior temporal, and cerebellum. No differences in QSM or R2* or cognition scores were found between both groups (p > 0.6654). No correlation was found between susceptibility and blood ion levels for cobalt or chromium in any region of the brain. No correlation was found between blood ion levels and cognition scores. Clinical significance: Results suggest that metal ions released by long-term and well-functioning implants do not affect brain integrity., (© 2024 The Authors. Journal of Orthopaedic Research® published by Wiley Periodicals LLC on behalf of Orthopaedic Research Society.)

Background: Corrosion at the head-neck junction of femoral stems is a rare complication of total hip arthroplasty (THA) with manifestations ranging from subclinical wear to failure. Prior studies have identified a single femoral component design with an increased propensity for catastrophic trunnion failure. The purpose of the present study was to quantify trunnion damage of this femoral component retrieved from patients undergoing revision THA for non-trunnionosis indications., Methods: 24 femoral components from a single manufacturer were identified for study inclusion. Each prosthesis underwent stereomicroscopic inspection. Corrosion and fretting scores were assigned per the Goldberg criteria to quadrants of the trunnion. Material loss was calculated based on cone angles across trunnion quadrants. This was carried out using a coordinate measuring machine that digitised each trunnion surface. Stems were compared to a series of femoral stems with the same trunnion design., Results: 20 of the 24 (83%) trunnions demonstrated corrosion, all 24 trunnions demonstrated fretting. Corrosion scores did not statistically differ with respect to trunnion zone ( p  = 0.53), while fretting scores were higher in the inferior compared to the superior zones ( p   <  0.001). There was no significant difference in cone angles assessing material loss between stems ( p  = 0.25)., Conclusions: Evidence of trunnion damage was observed in each stem retrieved for non-trunnionosis revision. Fretting occurred more frequently about the inferior quadrants. However, digitised trunnion shapes were similar between compared stems exhibiting no material loss. Therefore, it is possible that previous reports of trunnion failures for this implant are not a systemic issue, and that further investigation is required., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Copper is one of a handful of biologically necessary heavy metals that is also a common environmental pollutant. Under normal conditions, copper ions are required for many key physiological processes. However, in excess, copper results in cell and tissue damage ranging in severity from temporary injury to permanent neurological damage. Because of its biological relevance, and because many conserved copper-responsive genes respond to nonessential heavy metal pollutants, copper resistance in Drosophila melanogaster is a useful model system with which to investigate the genetic control of the heavy metal stress response. Because heavy metal toxicity has the potential to differently impact specific tissues, we genetically characterized the control of the gene expression response to copper stress in a tissue-specific manner in this study. We assessed the copper stress response in head and gut tissue of 96 inbred strains from the Drosophila Synthetic Population Resource using a combination of differential expression analysis and expression quantitative trait locus mapping. Differential expression analysis revealed clear patterns of tissue-specific expression. Tissue and treatment specific responses to copper stress were also detected using expression quantitative trait locus mapping. Expression quantitative trait locus associated with MtnA, Mdr49, Mdr50, and Sod3 exhibited both genotype-by-tissue and genotype-by-treatment effects on gene expression under copper stress, illuminating tissue- and treatment-specific patterns of gene expression control. Together, our data build a nuanced description of the roles and interactions between allelic and expression variation in copper-responsive genes, provide valuable insight into the genomic architecture of susceptibility to metal toxicity, and highlight candidate genes for future functional characterization., Competing Interests: Conflicts of interest The authors declare no conflicts of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Genetics Society of America.)

Background: The objective of this study was to identify the rate and risk factors for revision total knee arthroplasty (TKA) within the first 5 years postoperative. Our secondary objective was to identify the rate of additional surgical procedures and death., Methods: We conducted a retrospective cohort study among patients in Ontario, Canada who underwent an elective, primary TKA between April 1, 2007, and March 31, 2014, for osteoarthritis. We excluded patients under 40 years and who had undergone a TKA within the previous 15 years. Our final study cohort included 94,193 patients. We reported the proportion of the study cohort who experienced revision surgery within 2 and 5 years of the primary TKA; secondary surgery within 5 years. We conducted Cochran-Armitage tests for trends to assess changes in the proportion of patients who experienced each of the study outcomes, and multivariable logistic regressions to evaluate predictors of a revision TKA., Results: There were 3,112 (3.3%) patients who had a revision within 5 years, and 1,866 (2.0%) within 2 years of their primary TKA. 3,316 (3.5%) had a secondary surgery (0.6% patellar resurfacing; 1.6% manipulation; 1.3% synovectomy; 0.5% washout; 0.9% debridement). Lower age, men, lower income, higher comorbidity score, depression, previous arthroscopy, lower surgeon volume, and general anesthesia were all significant positive predictors of revision., Conclusions: In our study cohort, 2.0% of patients had a revision TKA within 2 years, and 3.3% within 5 years of their primary TKA. Preoperative identification of risk factors may reduce the future prevalence of revision TKAs., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Approximately 20% of patients are dissatisfied with their total knee arthroplasty (TKA). Identifying patients likely to be dissatisfied early in the recovery process could help reduce the number of dissatisfied patients. The purpose of this study was to create an easily administered short questionnaire to identify patients likely to be dissatisfied at 1 year post surgery early in the recovery process., Methods: The study included 275 patients who underwent primary TKA for osteoarthritis. Individual 3-month postsurgery questionnaire items from the Knee Injury and Osteoarthritis Outcome Score and Knee Society Knee Scoring System were pooled together and used as candidate items to create 3 different short questionnaires. Items included in each questionnaire were selected using least absolute shrinkage and selection operator logistic regressions, a backward elimination method, and theory-based approaches. The area under the curve for each short questionnaire was calculated to evaluate predictive performances., Results: All 3 questionnaires contained a small number of items and appeared to successfully predict 1-year postsurgery dissatisfaction early in the recovery process. The least absolute shrinkage and selection operator logistic regression, backward elimination, and theory-based questionnaires were comprised of 4, 7, and 5 items and had the area under the curve scores of 0.893, 0.902, and 0.890, respectively. A question evaluating rising from sitting and activities of daily living appeared in all of the created questionnaires., Conclusion: A short questionnaire that is easy to administer and interpret can effectively predict TKA patient dissatisfaction at 1 year post surgery early in the recovery process., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Purpose: To support primary care physicians (PCPs) and their patients with knee osteoarthritis (OA), we created a series of evidence-based whiteboard educational videos for patients with knee OA. In a previous study we piloted these videos with patients to understand their acceptability and impact. The purpose of this study was to explore PCPs' perspectives to understand the utility of novel patient education videos to support management., Materials and Method: We conducted a qualitative descriptive study using semi-structured interviews of newly practicing and resident PCPs after watching a series of patient education videos. A thematic analysis approach was used combining both inductive and research question driven coding, category formation, and theme identification., Results: Ten participants were included. Barriers to optimal management were identified including the challenge of patient adherence and access to non-operative treatments. PCPs indicated that the videos would support their management of patients with knee OA by (1) supporting credibility and building trust with their patient, (2) reinforcing patient understanding, and (3) enhancing their own management of patients., Conclusion: Future implementation of these resources with attention to barriers that may limit uptake is necessary and may optimize management of knee OA in primary care.IMPLICATIONS FOR REHABILITATIONThe provision of patient educational materials may support patient buy-in regarding appropriate management, enhance patient understanding, and improve physicians' future practice.Viewing these videos could potentially improve physicians' future resource use, recommendation of non-operative treatments, and the quality of their total knee replacement referrals, which has benefits to both the patient and the healthcare system.Perceived barriers to implementing evidence-based recommendations may pose a challenge for patients and clinicians and should be considered to help facilitate the uptake of educational interventions.

We use ATAC-seq to examine chromatin accessibility for four different tissues in Drosophila melanogaster: adult female brain, ovaries, and both wing and eye-antennal imaginal discs from males. Each tissue is assayed in eight different inbred strain genetic backgrounds, seven associated with a reference quality genome assembly. We develop a method for the quantile normalization of ATAC-seq fragments and test for differences in coverage among genotypes, tissues, and their interaction at 44099 peaks throughout the euchromatic genome. For the strains with reference quality genome assemblies, we correct ATAC-seq profiles for read mis-mapping due to nearby polymorphic structural variants (SVs). Comparing coverage among genotypes without accounting for SVs results in a highly elevated rate (55%) of identifying false positive differences in chromatin state between genotypes. After SV correction, we identify 1050, 30383, and 4508 regions whose peak heights are polymorphic among genotypes, among tissues, or exhibit genotype-by-tissue interactions, respectively. Finally, we identify 3988 candidate causative variants that explain at least 80% of the variance in chromatin state at nearby ATAC-seq peaks., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Huynh et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: Heavy metal pollutants can have long lasting negative impacts on ecosystem health and can shape the evolution of species. The persistent and ubiquitous nature of heavy metal pollution provides an opportunity to characterize the genetic mechanisms that contribute to metal resistance in natural populations. Methods: We examined variation in resistance to copper, a common heavy metal contaminant, using wild collections of the model organism Drosophila melanogaster . Flies were collected from multiple sites that varied in copper contamination risk. We characterized phenotypic variation in copper resistance within and among populations using bulked segregant analysis to identify regions of the genome that contribute to copper resistance. Results and Discussion: Copper resistance varied among wild populations with a clear correspondence between resistance level and historical exposure to copper. We identified 288 SNPs distributed across the genome associated with copper resistance. Many SNPs had population-specific effects, but some had consistent effects on copper resistance in all populations. Significant SNPs map to several novel candidate genes involved in refolding disrupted proteins, energy production, and mitochondrial function. We also identified one SNP with consistent effects on copper resistance in all populations near CG11825 , a gene involved in copper homeostasis and copper resistance. We compared the genetic signatures of copper resistance in the wild-derived populations to genetic control of copper resistance in the Drosophila Synthetic Population Resource (DSPR) and the Drosophila Genetic Reference Panel (DGRP), two copper-naïve laboratory populations. In addition to CG11825 , which was identified as a candidate gene in the wild-derived populations and previously in the DSPR, there was modest overlap of copper-associated SNPs between the wild-derived populations and laboratory populations. Thirty-one SNPs associated with copper resistance in wild-derived populations fell within regions of the genome that were associated with copper resistance in the DSPR in a prior study. Collectively, our results demonstrate that the genetic control of copper resistance is highly polygenic, and that several loci can be clearly linked to genes involved in heavy metal toxicity response. The mixture of parallel and population-specific SNPs points to a complex interplay between genetic background and the selection regime that modifies the effects of genetic variation on copper resistance., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Everman, Macdonald and Kelly.)

The germline mobilization of transposable elements (TEs) by small RNA mediated silencing pathways is conserved across eukaryotes and critical for ensuring the integrity of gamete genomes. However, genomes are recurrently invaded by novel TEs through horizontal transfer. These invading TEs are not targeted by host small RNAs, and their unregulated activity can cause DNA damage in germline cells and ultimately lead to sterility. Here we use hybrid dysgenesis-a sterility syndrome of Drosophila caused by transposition of invading P-element DNA transposons-to uncover host genetic variants that modulate dysgenic sterility. Using a panel of highly recombinant inbred lines of Drosophila melanogaster, we identified two linked quantitative trait loci (QTL) that determine the severity of dysgenic sterility in young and old females, respectively. We show that ovaries of fertile genotypes exhibit increased expression of splicing factors that suppress the production of transposase encoding transcripts, which likely reduces the transposition rate and associated DNA damage. We also show that fertile alleles are associated with decreased sensitivity to double-stranded breaks and enhanced DNA repair, explaining their ability to withstand high germline transposition rates. Together, our work reveals a diversity of mechanisms whereby host genotype modulates the cost of an invading TE, and points to genetic variants that were likely beneficial during the P-element invasion., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2022 Lama et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Drosophila melanogaster has proved an effective system with which to understand the evolutionary genetics and molecular mechanisms of insecticide resistance. Insecticide use has left signatures of selection in the fly genome, and both functional and quantitative genetic studies in the system have identified genes and variants associated with resistance. Here, we use D. melanogaster and leverage a bulk phenotyping and pooled sequencing "extreme quantitative trait loci" approach to genetically dissect variation in resistance to malathion, an organophosphate insecticide. We resolve 2 quantitative trait loci, one of which implicates allelic variation at the cytochrome P450 gene Cyp6g1, a strong candidate based on previous work. The second shows no overlap with hits from a previous genome-wide association study for malathion resistance, recapitulating other studies showing that different strategies for complex trait dissection in flies can yield apparently different architectures. Notably, we see no genetic signal at the Ace gene. Ace encodes the target of organophosphate insecticide inhibition, and genome-wide association studies have identified strong Ace-linked associations with resistance in flies. The absence of quantitative trait locus implicating Ace here is most likely because our mapping population does not segregate for several of the known functional polymorphisms impacting resistance at Ace, perhaps because our population is derived from flies collected prior to the widespread use of organophosphate insecticides. Our fundamental approach can be an efficient, powerful strategy to dissect genetic variation in resistance traits. Nonetheless, studies seeking to interrogate contemporary insecticide resistance variation may benefit from deriving mapping populations from more recently collected strains., (© The Author(s) 2022. Published by Oxford University Press on behalf of Genetics Society of America.)

We examined the effect of developmental exposure to three heavy metals - cadmium, copper, and lead - on gene expression in adult head tissue in the model organism Drosophila melanogaster . All metals affected development time and/or gene expression level. While variation in the response to each metal was apparent, two differentially-expressed genes were upregulated in response to all three metal treatments, and 11 genes were downregulated in two of the three treatments. Our work reveals that developmental metal exposure has the potential to have long-lasting, metal-specific effects on gene expression in adults, even after the metal stress has been removed., (Copyright: © 2022 by the authors.)

Background: In March 2020, an emergency was declared in the province of Ontario owing to the COVID-19 pandemic. From March 19 to May 26, all elective total hip arthroplasty (THA) and total knee arthroplasty (TKA) procedures were deferred. The purpose of this study was to review the unit sales data of THA and TKA procedures in Ontario over this time period to identify any trends in surgical activity., Methods: Unit sales data for all THA and TKA procedures performed in Ontario between January 2019 and December 2020 were reviewed. All orthopedic companies contributed to the data set. Femoral stems were considered an indicator of THA procedures, while primary femurs were considered an indicator of TKA procedures. Data were analyzed to determine trends in THA and TKA procedures during the deferral period and the relative change in THA and TKA activity following resumption., Results: There was a 53% reduction in THA activity between March and May of 2020 when compared to the same interval in 2019. From June to September of 2019, THA sales activity was 87.3% that of TKA. From June to September of 2020, THA sales activity was 122.8% that of TKA., Conclusion: Provincial directives aimed at controlling the outbreak of COVID-19 contributed to a substantial reduction in THA and TKA activity in 2020. Compared to 2019, there was a disproportionate increase in THA compared to TKA activity in 2020 following resumption of surgical services. These data have implications in recovery planning for the surgical backlog of THA in Ontario., (Crown Copyright © 2022. Published by Elsevier Inc. All rights reserved.)

Background: Bone loss remains an anticipated challenge in revision total knee arthroplasty (rTKA). Recent efforts to enhance rTKA fixation and stability have focused on metaphyseal implants, namely cones and sleeves. We sought to compare cone and sleeve implant survivorship in rTKA., Methods: One hundred eighty patients who underwent rTKA with metaphyseal implants from 2005 to 2018 were retrospectively reviewed. A total of 83 cones (22 femoral, 62 tibial) and 121 sleeves (58 femoral, 63 tibial) were identified. The mean age at the time of surgery was 72 years (range 43-97). Intraoperative Anderson Orthopaedic Research Institute bone loss classifications included the following: type 2A (25), type 2B (98), and type 3 (81). Mean follow-up was 41 months., Results: Revision-free survival for cones was 91.3% vs 92.2% for sleeves (P = .29). Twelve knees (4 cones, 8 sleeves) underwent irrigation, debridement, and polyethylene exchange with metaphyseal implant retention for acute postoperative periprosthetic joint infection (PJI). Development of chronic PJI warranted removal of 7 cones (8.4%), 6 of which were initially placed as part of a 2-stage revision TKA. Eight sleeves (6.6%) were removed for PJI, with all initially placed during a second stage reimplantation. In the absence of infection, survival was 100% and 99.1% for cones and sleeves, respectively. One sleeve was revised for periprosthetic fracture., Conclusion: Metaphyseal cones and sleeves offer equally durable survivorship in revision TKA. PJI was the most common mode of implant failure in this series. Importantly, no cases of cone or sleeve aseptic loosening were observed., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Purpose: To optimize non-operative management and decision making surrounding TKR we created educational whiteboard videos for patients with knee OA. The purpose of this study was to pilot our educational videos with end-users (patients) to determine patients' experiences and perspectives regarding the content and clarity of videos and to better understand their potential impact on patient's health behaviour., Materials and Methods: This was a mixed methods evaluation, using a qualitative descriptive approach, of patients attending their first consultation with an arthroplasty surgeon for TKR. We conducted in-depth semi-structured interviews with patients. Three members of the research team coded data independently, implementing a thematic analysis., Results: Thirteen participants were included. Participants indicated that the videos enhanced their confidence and clarity surrounding their decision to undergo TKR. The videos also addressed several knowledge gaps in their understanding of OA management. Barriers to uptake of the education were identified including limited access to PTs and the challenge of weight loss. Conclusions : The current educational intervention was valued by patients with knee OA. Implementation of these videos may have important implications for patients, providers, and our health care system.IMPLICATIONS FOR REHABILITATIONPatients with knee OA referred by primary care physicians to arthroplasty surgeons have knowledge gaps that may influence their self-management and decision making surrounding their condition.Educational materials can address these gaps and support patients in their understanding and management of their condition, which may have important downstream implications.Barriers to accessing non-operative care including physiotherapy must be pre-emptively addressed to ensure that enhanced knowledge is met with improved access for patients.

This study examined the association and level of agreement between criterion methods and the Apple Watch 4® and Fitbit Charge 3® for recording step count and heart rate when exercising in water on an aquatic treadmill (ATM). Sixteen healthy participants (13 females and 3 males) volunteered to take part in this study. Participants were submerged in an ATM pool to the level of their xiphoid process and completed 3-min exercise bouts at intensities that corresponded to a comfortable walk, brisk walk, jog, and running. A Polar® T31 chest strap recorded heart rate (HR) and a high-definition digital camera was utilized for recording step count (SC). Significant associations (p < 0.001) were observed between criterion methods and the Apple® (HR: R 2  = 0.99 and SC: R 2  = 0.87) and Fitbit® (HR: R 2  = 0.72 and SC: R 2  = 0.83) devices. The mean absolute error and relative error (%) for recording step count were 19.8 (7.4%) in the Apple Watch and 21.4 (8.5%) in the Fitbit and 0.90 (0.76%) in the Apple Watch and 4.2 (3.0%) in the Fitbit for recording heart rate. Both devices displayed a reasonable level of agreement for recording step count and heart rate when exercising in water. Linear regression analysis demonstrating the association between each wearable device and the Apple Watch and Fit Bit Charge for recording step count and heart rate., (© 2022. International Federation for Medical and Biological Engineering.)

Despite the value of recombinant inbred lines for the dissection of complex traits, large panels can be difficult to maintain, distribute, and phenotype. An attractive alternative to recombinant inbred lines for many traits leverages selecting phenotypically extreme individuals from a segregating population, and subjecting pools of selected and control individuals to sequencing. Under a bulked or extreme segregant analysis paradigm, genomic regions contributing to trait variation are revealed as frequency differences between pools. Here, we describe such an extreme quantitative trait locus, or extreme quantitative trait loci, mapping strategy that builds on an existing multiparental population, the Drosophila Synthetic Population Resource, and involves phenotyping and genotyping a population derived by mixing hundreds of Drosophila Synthetic Population Resource recombinant inbred lines. Simulations demonstrate that challenging, yet experimentally tractable extreme quantitative trait loci designs (≥4 replicates, ≥5,000 individuals/replicate, and selecting the 5-10% most extreme animals) yield at least the same power as traditional recombinant inbred line-based quantitative trait loci mapping and can localize variants with sub-centimorgan resolution. We empirically demonstrate the effectiveness of the approach using a 4-fold replicated extreme quantitative trait loci experiment that identifies 7 quantitative trait loci for caffeine resistance. Two mapped extreme quantitative trait loci factors replicate loci previously identified in recombinant inbred lines, 6/7 are associated with excellent candidate genes, and RNAi knock-downs support the involvement of 4 genes in the genetic control of trait variation. For many traits of interest to drosophilists, a bulked phenotyping/genotyping extreme quantitative trait loci design has considerable advantages., (© The Author(s) 2022. Published by Oxford University Press on behalf of Genetics Society of America. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Approximately 20% of total knee arthroplasty (TKA) patients are found to be dissatisfied or unsure of their satisfaction at 1-year post-surgery. This study attempted to predict 1-year post-surgery dissatisfied/unsure TKA patients with pre-surgery and surgical variables using logistic regression and machine learning methods., Methods: A retrospective analysis of patients who underwent primary TKA for osteoarthritis between 2012 and 2016 at a single institution was completed. Patients were split into satisfied and dissatisfied/unsure groups. Potential predictor variables included the following: demographic information, patella re-surfaced, posterior collateral ligament sacrificed, and subscales from the Knee Society Knee Scoring System, the Knee Society Clinical Rating System, the Western Ontario and McMaster Universities Osteoarthritis Index, and the 12-Item Short Form Health Survey version 2. Logistic regression and 6 different machine learning methods were used to create prediction models. Model performance was evaluated using discrimination (AUC [area under the receiver operating characteristic curve]) and calibration (Brier score, Cox intercept, and Cox slope) metrics., Results: There were 1432 eligible patients included in the analysis, 313 were considered to be dissatisfied/unsure. When evaluating discrimination, the logistic regression (AUC = 0.736) and extreme gradient boosted tree (AUC = 0.713) models performed best. When evaluating calibration, the logistic regression (Brier score = 0.141, Cox intercept = 0.241, and Cox slope = 1.31) and gradient boosted tree (Brier score = 0.149, Cox intercept = 0.054, and Cox slope = 1.158) models performed best., Conclusion: The models developed in this study do not perform well enough as discriminatory tools to be used in a clinical setting. Further work needs to be done to improve the performance of pre-surgery TKA dissatisfaction prediction models., (Copyright © 2021 Elsevier Inc. All rights reserved.)

We sought to evaluate wear and kinematics in well-established implants of posterior stabilized (PS) and cruciate retaining (CR) designs. Ninety-one knees implanted for at least five years were examined. The implants were Genesis II PS (Smith & Nephew, Memphis, TN), Sigma PS (DePuy Synthes, Warsaw, IN), or Sigma CR. Radiostereometric analysis (RSA) images were acquired at multiple flexion angles and the 3D positions of the implant components were determined using model-based RSA software. The location of the center of the contact area between the femoral and polyethylene components was used to obtain contact kinematics, and the magnitude of the virtual intersection between the components indicated linear wear. All three groups had paradoxical anterior motion on both condyles, experienced similar net external rotation, and exhibited instances of internal rotation during flexion. The maximum observed wear rate was significantly greater for the Sigma PS than the Genesis II PS on the medial condyle (mean difference = 0.032 mm/year, p = 0.044), but not the lateral condyle, while there was no difference between the Sigma PS and Sigma CR for either condyle. Knees with lateral condylar separation had greater maximum wear rates on the medial condyle (mean difference = 0.033 mm/year, p = 0.001), while those with medial condylar separation had greater maximum wear rates on the lateral condyle (mean difference = 0.044 mm/year, p = 0.014). At long term follow-up in patients with well-functioning implants, there were differences in kinematics and wear resistance between implants. These results suggest that implant design affects long-term kinematics and wear in well-functioning implants and that condylar separation should be avoided to minimize wear., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: The prevalence and outcomes of unexpected positive cultures (UPCs) of specimens taken during presumed aseptic revision total hip arthroplasty (THA) are unclear. The purpose of this study was to determine the prevalence of UPC and infection-free implant survival in this patient population. Secondary aims included identifying factors associated with subsequent infection-related failure in patients with UPC., Methods: We reviewed all THA revisions (n = 2,288) performed at our institution from 2006 to 2019. Presumed aseptic revision THAs with intraoperative culture(s) were eligible (n = 1,196), and those with UPC were included in a Kaplan-Meier analysis to determine the infection-free implant survival and in Cox regression analysis to identify factors associated with infection-related failure., Results: UPC(s) were documented for 9.2% (110) of 1,196 aseptic THA revisions. The 2- and 5-year infection-free implant survival in the entire UPC cohort was 93.1% (95% confidence interval [CI] = 90.5% to 95.7%) and 86.8% (95% CI = 82.9% to 90.7%), respectively. The 2- and 5-year infection-free survival with failure due to infection with the same microorganism as identified in the UPC as the end point was 95.8% (95% CI = 93.7% to 97.9%) and 94.3% (95% CI = 91.7% to 96.9%), respectively. Subsequent infection-related failures caused by the same microorganism as identified in the UPC were more likely to occur after revisions with ≥2 UPCs than after those with 1 UPC (p = 0.024). Revision due to adverse metal reaction was a risk factor for subsequent infection-related failure (hazard ratio [HR] = 14.49, 95% CI = 2.69 to 78.04). Patients with a single UPC who were not treated with antibiotics had no subsequent periprosthetic joint infections (PJIs) caused by the same microorganism as identified in the UPC., Conclusions: The prevalence of UPC was 9.2%, and the infection-free implant survival in patients with UPC is encouraging. Implant survival free of PJI caused by the same microorganism as identified in the UPC was excellent. Aseptic revision for adverse metal reaction was a risk factor for subsequent PJI in patients with UPC. No patient with a single UPC who was not treated with antibiotics developed PJI caused by the UPC-identified microorganism, suggesting that in the absence of other signs of infection a single UPC does not warrant antibiotic treatment., Level of Evidence: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence., Competing Interests: Disclosure: The authors indicated that no external funding was received for any aspect of this work. The Disclosure of Potential Conflicts of Interest forms are provided with the online version of the article (http://links.lww.com/JBJS/G484)., (Copyright © 2021 by The Journal of Bone and Joint Surgery, Incorporated.)

Planobispora rosea is the natural producer of the potent thiopeptide antibiotic GE2270A. Here, we present the results of a metabolomics and transcriptomics analysis of P. rosea during production of GE2270A. The data generated provides useful insights into the biology of this genetically intractable bacterium. We characterize the details of the shutdown of protein biosynthesis and the respiratory chain associated with the end of the exponential growth phase. We also provide the first description of the phosphate regulon in P. rosea . Based on the transcriptomics data, we show that both phosphate and iron are limiting P. rosea growth in our experimental conditions. Additionally, we identified and validated a new biosynthetic gene cluster associated with the production of the siderophores benarthin and dibenarthin in P. rosea . Together, the metabolomics and transcriptomics data are used to inform and refine the very first genome-scale metabolic model for P. rosea , which will be a valuable framework for the interpretation of future studies of the biology of this interesting but poorly characterized species. IMPORTANCE Planobispora rosea is a genetically intractable bacterium used for the production of GE2270A on an industrial scale. GE2270A is a potent thiopeptide antibiotic currently used as a precursor for the synthesis of two compounds under clinical studies for the treatment of Clostridium difficile infection and acne. Here, we present the very first systematic multi-omics investigation of this important bacterium, which provides a much-needed detailed picture of the dynamics of metabolism of P. rosea while producing GE2270A.