The AAHKS Clinical Research Award: Extended Postoperative Oral Tranexamic Acid in Total Knee Arthroplasty: A Randomized Controlled Pilot Study.

BACKGROUND: Perioperative tranexamic acid (TXA) use with total knee arthroplasty (TKA) is widely accepted today. Recently, a few international groups have published on the safety and outcomes of extending TXA use in the postoperative period. Through a double-blinded, randomized control trial (RCT), we aimed to investigate the safety and clinical efficacy of extended postoperative oral TXA use in TKA performed in an American, free-standing ambulatory surgery center (ASC). METHODS: Based on a power analysis, 40 patients undergoing primary TKA were randomized into 2 groups: extended oral TXA versus placebo. Both groups received a standard 1g intravenous TXA dose prior to incision and at the time of closure. The extended TXA group received an additional 1.95 g oral TXA dose following ambulation the day of surgery, plus on postoperative days 1,2, and 3. Patients who had a history of venous thromboembolism (VTE) or cancer were excluded. All patients received 81 mg of aspirin twice daily for VTE prophylaxis. Patients were followed on postoperative day 3 and weeks 2 and 6. Paired t-tests determined statistical significance. RESULTS: Extended TXA patients showed significantly increased knee flexion at 6 weeks (116.05 versus 106.5, P = .0308), improved VAS at 2 (2.5 versus 3.85, P = .039) and 6 weeks (1.35 versus 2.8, P = .011), and superior KOOS JR at 2 (66.87 versus 60.63, P = .03) and 6 weeks (73.33 versus 62.47, P = .0019) compared to placebo patients. No significant differences were found for changes in hemoglobin levels at any time points. No significant differences were found at 12 weeks for any clinical endpoints. No adverse events were noted in either cohort. CONCLUSIONS: When compared to placebo, the extended use of oral TXA in the postoperative period may safely result in improved motion, pain, and functional scores. Further investigation into 1-to-2-year outcomes, as well as the duration and dose of postoperative TXA use is warranted.

Hip Arthroplasty Femoral Stem Designs and Their Association With Early Postoperative Periprosthetic Femoral Fractures.

BACKGROUND: Periprosthetic femoral fractures (PFFs) in total hip arthroplasty (THA), especially those in contact with the diaphyseal stem, carry high morbidity. This study evaluated how stem design influences the risk of early Vancouver B PFF or other PFF requiring operative intervention after THA. METHODS: A multicenter, retrospective study of 3,433 primary cementless THAs performed from 2014 to 2021 included 2,302 single-taper (micro M/L [n = 1,169]; M/L [n = 1,133]) and 1,131 double-taper (fit-and-fill [n = 420]; compaction-collared [n = 711]) stems. Mean follow-up was 2.2 years (range, 0.3 to 6.5 years). Primary outcomes were Vancouver B and surgically treated postoperative PFFs among differing femoral stems. Secondary outcomes included rates of intraoperative and postoperative Vancouver A and C PFFs. RESULTS: Forty five postoperative PFFs (1.3%) occurred within 8.8 weeks (median), 25 of which were Vancouver B (0.7%) and 20 total PFFs that required operative intervention (0.6%). Compaction-collared stems had a decreased risk of Vancouver B (hazard ratio 0.18, 95% confidence interval: 0.03-0.97 P = .044) and any surgically treated PFF (hazard ratio 0.10, 95% confidence interval: 0.01-0.95; P = .037). Intraoperative PFFs were most common with fit-and-fill stems (3.6%, P < .001) and Vancouver A with compaction-collared stems (1.8%, P < .001). The cohort with PFF had a higher Charlson comorbidity index (P = .004), more women (P = .001), more Dorr A or C femora (P = .013), and more posterior or lateral surgical approaches compared to those without PFF (P ≤ .001). CONCLUSION: After controlling for confounding variables, compaction-collared stems had a significantly lower risk of postoperative Vancouver B and PFF requiring operative treatment than single-taper and double-taper stems.

GATA4 and estrogen receptor alpha bind at SNPs rs9921222 and rs10794639 to regulate AXIN1 expression in osteoblasts.

Osteoporosis is a serious public health problem that affects 200 million people worldwide. Genome-wide association studies have revealed the association between several single nucleotide polymorphisms (SNPs) near WNT/ß-catenin signaling genes and bone mineral density (BMD). The activation of ß-catenin by WNT ligands is required for osteoblast differentiation. SNP rs9921222 is an intronic variant of AXIN1 (a scaffold protein in the destruction complex that regulates ß-catenin signaling) that correlates with BMD. However, the biological mechanism of SNP rs9921222 has never been reported. Here, we show that the genotype of SNP rs9921222 correlates with the expression of AXIN1 in human osteoblasts. RNA and genomic DNA were analyzed from primary osteoblasts from 111 different individuals. Homozygous TT at rs9921222 correlates with a higher expression of AXIN1 than homozygous CC. Regional association analysis showed that rs9921222 is in high linkage disequilibrium (LD) with SNP rs10794639. In silico transcription factor analysis predicted that rs9921222 is within a GATA4 motif and rs10794639 is adjacent to an estrogen receptor alpha (ERα) motif. Mechanistically, GATA4 and ERα bind at SNPs rs9921222 and rs10794639 as detected by ChIP-qPCR. Luciferase assays demonstrate that rs9921222 is the causal SNP to alter ERα and GATA4 binding. GATA4 promoted the expression, and in contrast, ERα suppressed the expression of AXIN1 via the histone deacetylase complex member SIN3A. Functionally, the level of AXIN1 negatively correlates with the level of transcriptionally active ß-catenin. In summary, we have discovered a molecular mechanism of the SNP rs9921222 to regulate AXIN1 through GATA4 and ERα binding in human osteoblasts.

Estrogen receptor alpha and NFATc1 bind to a bone mineral density-associated SNP to repress WNT5B in osteoblasts.

Genetic factors and estrogen deficiency contribute to the development of osteoporosis. The single-nucleotide polymorphism (SNP) rs2887571 is predicted from genome-wide association studies (GWASs) to associate with osteoporosis but has had an unknown mechanism. Analysis of osteoblasts from 110 different individuals who underwent joint replacement revealed that the genotype of rs2887571 correlates with WNT5B expression. Analysis of our ChIP-sequencing data revealed that SNP rs2887571 overlaps with an estrogen receptor alpha (ERα) binding site. Here we show that 17ß-estradiol (E2) suppresses WNT5B expression and further demonstrate the mechanism of ERα binding at the enhancer containing rs2887571 to suppress WNT5B expression differentially in each genotype. ERα interacts with NFATc1, which is predicted to bind directly at rs2887571. CRISPR-Cas9 and ChIP-qPCR experiments confirm differential regulation of WNT5B between each allele. Homozygous GG has a higher binding affinity for ERα than homozygous AA and results in greater suppression of WNT5B expression. Functionally, WNT5B represses alkaline phosphatase expression and activity, decreasing osteoblast differentiation and mineralization. Furthermore, WNT5B increases interleukin-6 expression and suppresses E2-induced expression of alkaline phosphatase during osteoblast differentiation. We show that WNT5B suppresses the differentiation of osteoblasts via receptor tyrosine kinase-like orphan receptor 1/2 (ROR1/2), which activates DVL2/3/RAC1/CDC42/JNK/SIN3A signaling and inhibits ß-catenin activity. Together, our data provide mechanistic insight into how ERα and NFATc1 regulate the non-coding SNP rs2887571, as well as the function of WNT5B on osteoblasts, which could provide alternative therapeutic targets for osteoporosis.

Cryoneurolysis before Total Knee Arthroplasty in Patients With Severe Osteoarthritis for Reduction of Postoperative Pain and Opioid Use in a Single-Center Randomized Controlled Trial.

BACKGROUND: We hypothesized that preoperative cryoneurolysis of the superficial genicular nerves in patients with osteoarthritis would decrease postoperative opioid use relative to standard of care (SOC) treatment in patients undergoing total knee arthroplasty (TKA). METHODS: Patients received either cryoneurolysis (intent-to-treat [ITT]: n = 62) or SOC (ITT: n = 62). The cryoneurolysis group received cryoneurolysis of the superficial genicular nerves 3-7 days before surgery plus a similar preoperative, intraoperative, and postoperative pain management protocol as the SOC group. The primary end point was cumulative opioid consumption in total daily morphine equivalents from discharge to the 6-week study follow-up assessment. Secondary end points included changes in pain and functional scores. Primary and secondary end points were assessed using ITT and per-protocol (PP) analyses. RESULTS: The primary end point was not met in the ITT analysis (4.8 [cryoneurolysis] vs 6.1 [SOC] mg; P = .0841) but was met in the PP analysis (4.2 vs 5.9 mg; P = .0186) after excluding patients with medication deviations or missing follow-up data. Compared with the SOC group, the cryoneurolysis group had improved functional scores and numerical improvements in pain scores across all follow-up assessments, with significant improvements observed in current pain from baseline to the 72-hour and 2-week follow-up assessments and pain in the past week from baseline to the 12-week follow-up assessment. CONCLUSION: Findings from the PP analysis suggest that preoperative cryoneurolysis in patients with knee osteoarthritis can reduce opioid consumption and improve functional outcomes after TKA.

Biomechanical validation of medial pie-crusting for soft-tissue balancing in knee arthroplasty.

Balancing a varus knee is traditionally accomplished by releasing the medial soft-tissue sleeve off the tibia. Recently, "pie-crusting" (PC) medial structures has been described. In a biomechanical cadaver study we compared PC to traditional release (TR) to determine their effects on flexion and extension gaps. PC was done in five specimens along the anterior half of the medial soft-tissue sleeve and five along the posterior half, followed by a traditional release. In 90° flexion, valgus laxity after TR was significantly greater than after PC alone. PC of the anterior or posterior aspect of the medial soft-tissue sleeve can effect changes more in flexion than in extension, respectively. Complete TR did not provide more gap opening than PC in extension, but produced more effect in flexion.

Accuracy and precision of two computer-assisted methods of radiographic wear measurement in total hip arthroplasty.

Roentgen Monographic Analysis Tool (ROMAN) and Hip Analysis Suite (HAS) were used to analyze radiographs of a phantom hip model. Displacements of known magnitude and direction were produced using dial micrometers. Differences between the known displacement and the programs' reported displacement were compared. Hip Analysis Suite was superior with a median error of 0.075 mm (range, 0.019-0.205 mm) compared with 0.137 mm (range, 0.008-0.389 mm) for ROMAN (P = .002). Hip Analysis Suite was also more precise when evaluating intraobserver variability, with a standard deviation between radiographs of 0.007 mm (range, 0.002-0.009 mm), whereas ROMAN's standard deviation was 0.117 mm (range, 0.007-0.153 mm). Repeatability for HAS was 0.019 mm and 0.325 mm for ROMAN. Hip Analysis Suite was more accurate and precise than ROMAN under experimental conditions with digital radiographs.

A comparison of workers' compensation patients and nonworkers' compensation patients undergoing endoscopic carpal tunnel release.

This study compares results of endoscopic carpal tunnel release using the two-portal technique in two groups of patients based on whether or not they were receiving workers' compensation. There were 50 patients in the worker's compensation group and 63 in the nonworker's compensation group. Mean follow-up was 40.8 months and 44.8 months, respectively. Duration of symptoms before surgery was statistically different in the two groups, 13.6 months in the worker's compensation groups compared to 26.2 months in the nonworker's compensation group. Worker's compensation patients tended to be younger, have shorter duration of symptoms before surgery, report lower postoperative activity levels, have more subsequent surgeries, and have mediocre results when compared to nonworker's compensation patients. There was no statistically significant difference in the rate or timing of return to work. Our series of 113 patients who had endoscopic carpal tunnel release indicates that careful patient selection is necessary to achieve satisfactory outcomes in worker's compensation patients.

Total knee arthroplasty with asymmetric femoral condyles and tibial tray.

Total knee arthroplasties with an asymmetric tibial tray and posterior femoral condyles were implanted in 224 knees. Follow-up averaged 6.3 years. All components were cemented, all patellae were resurfaced, and all femoral components were cruciate-substituting. Postoperative alignment averaged 3.3 degrees valgus. Radiolucencies were absent around 116 knees (66%). No components were radiographically loose. Knee Society scores averaged 85 postoperatively and modified Western Ontario and McMaster Universities Index scores averaged 82. Postoperative flexion averaged 114 degrees. Ten knees required manipulation for arthrofibrosis. Lateral release was necessary in 62 knees (28%). No revisions were required for aseptic loosening. Survivorship free of additional surgical procedures was 97% at 5 years. Compared with other series by designing surgeons, similar excellent survivorship was seen but with a higher lateral release rate.

Intermediate-term results with a modified antiprotrusio cage in acetabular revision surgery.

A modified antiprotrusio cage and cemented cup were implanted in 11 patients who required acetabular revision surgery. Acetabular defects were classified as combined in 8 hips, pelvic discontinuity in 2, and cavitary in 1. Cancellous allograft was used in all patients, and 4 required structural allografts. Mean operative time was 324 minutes (range, 273-434 minutes), and mean estimated blood loss was 1168 mL (range, 500-4000 mL). Mean clinical and radiographic follow-up was 6.1 years (range, 2-8.8 years). Aseptic loosening occurred in 2 hips, 1 of which was revised. There were no dislocations, no deep infections, and no neurovascular injuries. Mean postoperative Harris hip score was 76 (range, 49-97). In a comparison with historical controls, this cage, which facilitates anteversion of the cemented cup, was found to improve hip stability. Massive defects and poor ischial fixation were common in the cases of loosening.

Polyethylene sterilized without irradiation in a polished uncemented acetabular component-a clinical and radiographic analysis.

Clinical and radiographic analysis of the Reflection uncemented acetabular component was performed. Features of this component include a polished inner shell and ethylene oxide sterilization. Clinical information was available for 158 hips (mean, 4.6 years follow-up). A total of 19 hips have undergone or were recommended revision, 8 for aseptic loosening or wear (5%). Wear analysis was performed for 38 hips with more than 5 years of follow-up (mean, 6.7 years). Osteolysis was present in 20 of these patients. Penetration rate averaged 0.15 mm/y. Patients with uncemented femoral fixation (vs cemented) had a significantly higher penetration rate. Increased volumetric wear was seen with uncemented femoral fixation, thin liners, and ceramic heads. This component demonstrated relatively high penetration and osteolysis rates. Continued surveillance is recommended, particularly for active patients with thin liners.

Knee arthrodesis using an intramedullary nail.

Fifteen knee arthrodeses using an intramedullary nail were performed in 15 patients. Indications included 11 failed total knee arthroplasties (10 of 11 septic). A retrospective review revealed 100% fusion rate. Complications included 4 cases of painful hardware, 1 trochanteric bursitis, and 1 deep infection. Ten patients were available for assessment at 7 years follow-up. Average leg length discrepancy was 3.7 cm. Anatomic axis averaged 1.3 degrees valgus. Flexion angle averaged 3.5 degrees . Compared with age-matched controls, our patients fared significantly worse in physical functioning, physical role, bodily pain, vitality, and social functioning. Arthrodesis of the knee with an intramedullary nail provides a reliable means of fusion with reasonable alignment. These patients have high rates of pain and diminished functional status.