Association of synovial fluid and urinary C2C-HUSA levels with surgical outcomes post-total knee arthroplasty.

OBJECTIVES: After total knee arthroplasty (TKA), ∼30% of knee osteoarthritis (KOA) patients show little symptomatic improvement. Earlier studies have correlated urinary (u) type 2 collagen C terminal cleavage peptide assay (C2C-HUSA), which detects a fragment of cartilage collagen breakdown, with KOA progression. This study determines whether C2C levels in urine, synovial fluid, or their ratio, are associated with post-surgical outcomes. METHODS: From a large sample of 489 subjects, diagnosed with primary KOA undergoing TKA, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain and function scores were collected at baseline (time of surgery) and one-year post-TKA. Baseline urine (u) and synovial fluid (sf) were analysed using the IBEX-C2C-HUSA assay, with higher values indicating higher amounts of cartilage degradation. For urine, results were normalised to creatinine. Furthermore, subjects' changes in WOMAC scores were categorised based on percent reduction in pain or improvement in function, compared to baseline, such that >66.7%, >33.3 to ≤66.7%, and ≤33.3% denoted "strong", "moderate" and "mild/worse" responses, respectively. Associations of individual biofluid C2C-HUSA levels, or their ratio, with change in WOMAC pain and function scores up to one-year post-TKA, or category of change, were analysed by linear, logistic, or cumulative odds models. RESULTS: Higher baseline uC2C-HUSA levels or a lower ratio of baseline sfC2C-HUSA to uC2C-HUSA were associated with improvements in WOMAC pain by linear multivariable modelling [odds ratio -0.40 (95% confidence interval -0.76, -0.05) p = 0.03; 0.36 (0.01, 0.71), p = 0.04, respectively], while sfC2C-HUSA alone was not. However, lower ratios of sfC2C-HUSA to uC2C-HUSA were associated with improvements in WOMAC function [1.37 (0.18, 2.55), p = 0.02], while sfC2C-HUSA and uC2C-HUSA alone were not. Lower ratios of sfC2C-HUSA to uC2C-HUSA were also associated with an increased likelihood of a subject being categorised in a group where TKA was beneficial in both univariable [pain, 0.81 (0.68, 0.96), p = 0.02; function, 0.92 (0.85, 0.99), p = 0.035] and multivariable [pain, 0.81 (0.68, 0.97) p = 0.02; function, 0.92 (0.85, 1.00), p = 0.043] ordinal modelling, while sfC2C-HUSA and uC2C-HUSA alone were not. CONCLUSIONS: Overall, ratios of baseline sfC2C-HUSA to uC2C-HUSA, and baseline uC2C-HUSA, may play an important role in studying post-TKA surgical outcomes.

Evaluation of Trends in Knee Arthroscopy from 2004 to 2019 in Ontario, Canada.

BACKGROUND: How changes in recommendations for the use of knee arthroscopy have influenced real-world practice remains unclear. We assessed temporal trends in knee arthroscopy volume, costs, and rates of progression to knee arthroplasty following arthroscopy in Ontario, Canada. METHODS: We used diagnostic codes from population-based administrative databases from Ontario, Canada, to identify patients who underwent knee arthroscopy from April 1, 2004 to March 31, 2019. We calculated arthroscopy volume, costs, and rates of progression to knee arthroplasty within 1, 2, and 5 years following arthroscopy. RESULTS: A total of 408,040 arthroscopy procedures were included. The number of procedures declined 8.9% from 24,070 in 2004/2005 to 21,930 in 2018/2019. The volume of arthroscopy for osteoarthritis declined by 77.9% between 2007/2008 and 2018/2019. For degenerative meniscus disorders, the volume increased by 57.6% between 2004/2005 and 2013/2014, and then declined by 34.6% between 2013/2014 and 2018/2019. Among patients with osteoarthritis, rates of progression to knee arthroplasty were 3.8%, 9.6%, and 16.0%, at 1, 2, and 5 years, respectively, compared with rates among patients with degenerative meniscal disorders, which were 1.6%, 4.1%, and 7.3% at 1, 2, and 5 years, respectively. Over this period, progression to knee arthroplasty rates declined across diagnosis groups. These trends remained after adjusting for patient, surgeon, and hospital characteristics. CONCLUSIONS: In Ontario, Canada, utilization of knee arthroscopy declined between 2004/2005 and 2018/2019, with a concomitant decline in the rates of progression to knee arthroplasty within 1 to 5 years. Among the possible interpretations, our data are consistent with the hypothesis that clinical practice evolved as evidence-based recommendations against the use of knee arthroscopy for degenerative diagnoses were promulgated. (Funded by the Toronto General and Western Hospital Foundation through the University Health Network­Schroeder Arthritis Institute.)

Phytochemical analysis and nephroprotective effect of cactus (Opuntia ficus-indica) cladodes on sodium dichromate-induced kidney injury in rats.

Environmental and occupational exposure to chromium compounds, especially hexavalent chromium, is widely recognized as potentially nephrotoxic in humans and animals. The present study aimed to assess the efficacy of cactus (Opuntia ficus-indica) against sodium dichromate-induced nephrotoxicity, oxidative stress, and genotoxicity. Cactus cladodes extract (CCE) was phytochemically studied and tested in vitro for its potential antioxidant activities. Additionally, the preventive effect of CCE against sodium dichromate-induced renal dysfunction in a Wistar rat model (24 rats) was evaluated. For this purpose, CCE at a dose of 100 mg/kg was orally administered, followed by 10 mg/kg sodium dichromate (intraperitoneal injection). After 40 days of treatment, the rats were sacrificed, and the kidneys were excised for histological, lipid peroxidation, and antioxidant enzyme analyses. The phenol, flavonoid, tannin, ascorbic acid, and carotenoid contents of CCE were considered to be important. Our analyses showed that 1 mL of CCE was equivalent to 982.5 ± 1.79 µg of gallic acid, 294.37 ± 0.84 µg of rutin, 234.78 ± 0.24 µg of catechin, 204.34 ± 1.53 µg of ascorbic acid, and 3.14 ± 0.51 µg of ß-carotene. In vivo, pretreatment with CCE was found to provide significant protection against sodium dichromate-induced nephrotoxicity by inhibiting lipid peroxidation, preserving normal antioxidant activities, and protecting renal tissues from lesions and DNA damage. The nephroprotective potential of CCE against sodium dichromate toxicity might be due to its antioxidant properties.

Publication of sports medicine-related randomized controlled trials registered in ClinicalTrials.gov.

BACKGROUND: There is increasing evidence that a significant proportion of randomized trials in medicine, and recently in orthopaedics, do not go on to publication. PURPOSE: The objectives of this study were (1) to determine publication rates of randomized controlled trials in sports medicine that have been registered with ClinicalTrials.gov (CTG) and (2) to compare the registration summaries of randomized trials on CTG with final published manuscripts on pertinent methodological variables. STUDY DESIGN: Systematic review. METHODS: Two independent investigators searched ClinicalTrials.gov for all closed and completed trials related to sports medicine until June 2009 using a text search strategy. The authors then searched for publications resulting from these registered trials in peer-reviewed journals that are indexed with MEDLINE and/or EMBASE as of February 2012 based on study authors and key words provided in the study protocol. Details of primary outcomes and secondary outcomes, study sponsors, and sample size were extracted and compared between registrations and publications. RESULTS: Of 34 closed and completed trials registered on CTG, there were 20 resultant publications in peer-reviewed journals (58.8%). There was no significant relationship between source of funding and rate of publication (P > .05). The authors found a discrepancy between the CTG registration summary and the manuscript in at least one methodological variable (primary/secondary outcomes, inclusion/exclusion criteria, sample size) in 16 of 20 (80.0%) articles and a discrepancy in the primary outcome in 8 of 20 (40.0%) published trials. CONCLUSION: Although registration of sports medicine trials in CTG does not consistently result in publication or disclosure of results at 32 months from the time of study completion, observed publication rates are higher than in other orthopaedic subspecialties. Changes are also frequently made to the final presentation of eligibility criteria and primary and secondary outcomes that are not reflected in the registered trial data.

Novel method for simultaneous quantification of phenotypic resistance to maturation, protease, reverse transcriptase, and integrase HIV inhibitors based on 3'Gag(p2/p7/p1/p6)/PR/RT/INT-recombinant viruses: a useful tool in the multitarget era of antiretroviral therapy.

Twenty-six antiretroviral drugs (ARVs), targeting five different steps in the life cycle of the human immunodeficiency virus type 1 (HIV-1), have been approved for the treatment of HIV-1 infection. Accordingly, HIV-1 phenotypic assays based on common cloning technology currently employ three, or possibly four, different recombinant viruses. Here, we describe a system to assess HIV-1 resistance to all drugs targeting the three viral enzymes as well as viral assembly using a single patient-derived, chimeric virus. Patient-derived p2-INT (gag-p2/NCp7/p1/p6/pol-PR/RT/IN) products were PCR amplified as a single fragment (3,428 bp) or two overlapping fragments (1,657 bp and 2,002 bp) and then recombined into a vector containing a near-full-length HIV-1 genome with the Saccharomyces cerevisiae uracil biosynthesis gene (URA3) replacing the 3,428 bp p2-INT segment (Dudley et al., Biotechniques 46:458-467, 2009). P2-INT-recombinant viruses were employed in drug susceptibility assays to test the activity of protease (PI), nucleoside/nucleotide reverse transcriptase (NRTI), nonnucleoside reverse transcriptase (NNRTI), and integrase strand-transfer (INSTI) inhibitors. Using a single standardized test (ViralARTS HIV), this new technology permits the rapid and automated quantification of phenotypic resistance for all known and candidate antiretroviral drugs targeting all viral enzymes (PR, RT, including polymerase and RNase H activities, and IN), some of the current and potential assembly inhibitors, and any drug targeting Pol or Gag precursor cleavage sites (relevant for PI and maturation inhibitors) This novel assay may be instrumental (i) in the development and clinical assessment of novel ARV drugs and (ii) to monitor patients failing prior complex treatment regimens.