Total knee replacement after high tibial osteotomy: time-to-event analysis and predictors

BACKGROUND:An important aim of high tibial osteotomy (HTO) is to prevent or delay the need for total knee replacement (TKR). We sought to estimate the frequency and timing of conversion from HTO to TKR and the factors associated with it.METHODS:We prospectively evaluated patients with osteoarthritis (OA) of the knee who underwent medial opening wedge HTO from 2002 to 2014 and analyzed the cumulative incidence of TKR in July 2019. The presence or absence of TKR on the HTO limb was identified from the orthopedic surgery reports and knee radiographs contained in the electronic medical records for each patient at London Health Sciences Centre. We used cumulative incidence curves to evaluate the primary outcome of time to TKR. We used multivariable Cox proportional hazards analysis to assess potential preoperative predictors including radiographic disease severity, malalignment, correction size, pain, sex, age, body mass index (BMI) and year of surgery.RESULTS:Among 556 patients who underwent 643 HTO procedures, the cumulative incidence of TKR was 5% (95% confidence interval [CI] 3%–7%) at 5 years and 21% (95% CI 17%–26%) at 10 years. With the Cox proportional hazards multivariable model, the following preoperative factors were significantly associated with an increased rate of conversion: radiographic OA severity (adjusted hazard ratio [HR] 1.96, 95% CI 1.12–3.45), pain (adjusted HR 0.85, 95% CI 0.75–0.96)], female sex (adjusted HR 1.67, 95% CI 1.08–2.58), age (adjusted HR 1.50 per 10 yr, 95% CI 1.17–1.93) and BMI (adjusted HR 1.31 per 5 kng/m², 95% CI 1.12–1.53).INTERPRETATION:We found that 79% of knees did not undergo TKR within 10 years after undergoing medial opening wedge HTO. The strongest predictor of conversion to TKR is greater radiographic disease at the time of HTO.

The burden of knee osteoarthritis (OA) on patients and health care systems is substantial and growing.¹ The current treatment strategy that relies largely on total knee replacement (TKR) for end-stage disease may not be sustainable.^2–5 Reduced quality of life and loss of productivity due to knee OA in middle-aged people in the workforce is particularly problematic.^5–8 The global prevalence of knee OA peaks at about 50 years of age.⁹ Worldwide, the estimated years lived with disability is 2.4 million for people younger than 50 years of age, the approximate age of peak prevalence for knee OA.^9,10 Accordingly, the number of middle-aged patients seeking treatment for knee OA, including TKR, is increasing. ¹¹ Joint replacement may not be the most appropriate treatment for these patients.¹² Earlier TKR is associated with prosthesis infection, ¹³ lower patient satisfaction¹⁴ and revision surgery;^15–18 about 25% of all TKRs are considered “likely inappropriate.”¹⁹ Clinicians have identified a clear treatment gap between exhausting nonoperative management and appropriateness for TKR, resulting in years of pain, decreased function, productivity losses and associated costs.^5–9,20,21 It is therefore imperative to identify additional effective treatments for the large group of patients with knee OA.Medial opening wedge high tibial osteotomy (HTO) is a limb realignment surgery intended for patients with medial compartment knee OA who are not suitable candidates for TKR because of less severe disease, younger age and greater physical demands. The purpose of HTO is to correct malalignment, thereby shifting load away from the more involved knee compartment and limit OA progression.^22,23 Substantial shifts in knee loading^24,25 have resulted in clinically important improvements in pain and function after HTO^26,27 and the procedure is cost-effective,^28,29 yet the surgery is uncommon in Canada.³⁰ Unlike the high and increasing rates of other knee surgical procedures including arthroscopy³¹ and TKR,³² rates of HTO remain low.^33,34High tibial osteotomy may help fill the treatment gap between nonsurgical treatments and definitive TKR. At the London Health Sciences Centre in London, Ontario, HTO is performed frequently with a goal of preventing or delaying the need for TKR. Thus, it is appropriate to investigate the duration of benefit of HTO, and the preoperative characteristics associated with it. When quantified as conversion from HTO to TKR, registries using administrative data enable large sample sizes (> 2500 patients) to estimate cumulative incidence of TKR.^30,35,36 However, there can be limitations in using only administrative data, including confirming the correct procedure, limb and diagnosis. Administrative data often lack detailed information assessed preoperatively, such as radiographic features (e.g., disease severity and lower limb alignment) and patient-reported outcome measures. Previously reported predictors of conversion to TKR such as female sex and greater age^30,35–39 may be influenced (perhaps confounded) by other clinical characteristics not typically included in administrative data. Therefore, our objective was to investigate the cumulative incidence of TKR after medial opening wedge HTO and potential predictors using data collected prospectively from a single Canadian centre that focuses on HTO. Specifically, we evaluated the time to conversion from HTO to TKR and investigated the association of HTO preoperative characteristics with subsequent TKR.     

Serum creatine kinase activity following forearm flexion isometric exercise

The purpose of this study was to compare serum creatine kinase (CK) activity following two forearm flexion isometric exercise regimens differing in work to rest ratio, and examine the CK response to a repeated bout of isometric exercise. Eleven males were tested on two sessions (bouts) spaced 1 week apart. For bout 1, five subjects (group A) performed a forearm flexion isometric exercise consisting of 40 10-s maximal contractions with 20-s inter-trial rests (10:20), while six (group B) performed 40 maximal 10-s contractions with 5-s inter-trial rests (10:5). The increase in serum CK activity following the 10:20 exercise (143%) was significantly greater than that following the 10:5 exercise (52%). The 10:20 exercise was also associated with greater tension generation over trials. One week later, both groups performed a bout of 10:20 exercise. A substantial reduction in the serum CK response was found following this second bout. The data suggest that for bout 1 the isometric exercise associated with the greater overall tension levels resulted in the greater CK response. However, when the 10:20 exercise was repeated 1 week later, a substantial reduction in the CK response was found which was unrelated to the tension generated.     

Polar lipids and pigments as biomarkers for the study of the microbial community structure of solar salterns

Whole community lipids and pigments have been examined over a 3–5-year period in commercial salterns located in the United States, Israel, and Spain. There were significant differences in the types of lipids and pigments within the California saltern system during the 5-year period. These patterns differed seasonally despite examination of ponds with approximately the same salinities. The solar saltern in Eilat, Israel had fewer lipids on the thin-layer chromatography plates and confirmed previous analyses. The biota in the crystallizer pond in Alicante, Spain, resembled the microbial community in Israel. In the crystallizers at all three locations, phosphatidyl glycerol, methyl-phosphatidyl glycerophosphate, phosphatidyl glycerosulfate, and the sulfated diglycosyldiether lipid were identified regardless of season. This was not true for pans with salinities below 25% where no distinctive pattern was observed. Thus, we hypothesize that the more eutrophic inlet waters of the California saltern and the cooler temperatures, which result in longer retention times of water in the different pans, allow for the more diverse microbial community to develop. This is reflected then in more complex lipid and pigment patterns. However, the oligotrophic inlet waters to the Eilat saltern coupled with a drier and warmer climate result in a shorter retention time of water in the pans and a less diverse microbial community as evidenced by fewer extractable lipids and pigments.     

Development of an unbiased statistical method for the analysis of unigenic evolution

Background  

Unigenic evolution is a powerful genetic strategy involving random mutagenesis of a single gene product to delineate functionally important domains of a protein. This method involves selection of variants of the protein which retain function, followed by statistical analysis comparing expected and observed mutation frequencies of each residue. Resultant mutability indices for each residue are averaged across a specified window of codons to identify hypomutable regions of the protein. As originally described, the effect of changes to the length of this averaging window was not fully eludicated. In addition, it was unclear when sufficient functional variants had been examined to conclude that residues conserved in all variants have important functional roles.