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Nav1.7 as a chondrocyte regulator and therapeutic target for osteoarthritis
Fu, Wenyu; Vasylyev, Dmytro; Bi, Yufei; Zhang, Mingshuang; Sun, Guodong; Khleborodova, Asya; Huang, Guiwu; Zhao, Libo; Zhou, Renpeng; Li, Yonggang; Liu, Shujun; Cai, Xianyi; He, Wenjun; Cui, Min; Zhao, Xiangli; Hettinghouse, Aubryanna; Good, Julia; Kim, Ellen; Strauss, Eric; Leucht, Philipp; Schwarzkopf, Ran; Guo, Edward X; Samuels, Jonathan; Hu, Wenhuo; Attur, Mukundan; Waxman, Stephen G; Liu, Chuan-Ju
Osteoarthritis (OA) is the most common joint disease. Currently there are no effective methods that simultaneously prevent joint degeneration and reduce pain1. Although limited evidence suggests the existence of voltage-gated sodium channels (VGSCs) in chondrocytes2, their expression and function in chondrocytes and in OA remain essentially unknown. Here we identify Nav1.7 as an OA-associated VGSC and demonstrate that human OA chondrocytes express functional Nav1.7 channels, with a density of 0.1 to 0.15 channels per µm2 and 350 to 525 channels per cell. Serial genetic ablation of Nav1.7 in multiple mouse models demonstrates that Nav1.7 expressed in dorsal root ganglia neurons is involved in pain, whereas Nav1.7 in chondrocytes regulates OA progression. Pharmacological blockade of Nav1.7 with selective or clinically used pan-Nav channel blockers significantly ameliorates the progression of structural joint damage, and reduces OA pain behaviour. Mechanistically, Nav1.7 blockers regulate intracellular Ca2+ signalling and the chondrocyte secretome, which in turn affects chondrocyte biology and OA progression. Identification of Nav1.7 as a novel chondrocyte-expressed, OA-associated channel uncovers a dual target for the development of disease-modifying and non-opioid pain relief treatment for OA.
PMCID:10794151
PMID: 38172636
ISSN: 1476-4687
CID: 5626502
Two-Year Outcomes of Novel Dual-Mobility Implant in Primary Total Hip Arthroplasty
Schaffler, Benjamin C; Raymond, Hayley E; Black, Collin S; Habibi, Akram A; Ehlers, Mallory; Duncan, Stephen T; Schwarzkopf, Ran
INTRODUCTION/UNASSIGNED:Dual-mobility (DM) implants for total hip arthroplasty (THA) have gained popularity due to their potential to reduce hip instability and dislocation events that may lead to revision surgery. These implants consist of a femoral head articulated within a polyethylene liner, which articulates within an outer acetabular shell, creating a dual-bearing surface. Our study aimed to report our observations on the survivorship of a novel DM implant for primary total hip arthroplasty at two years. METHODS/UNASSIGNED:We conducted a retrospective, multicenter study to assess the clinical outcomes of patients undergoing a THA with a novel DM implant (OR3O acetabular system™, Smith & Nephew, Inc., Memphis, TN) from January 2020 to September 2021. Patient demographics, surgical information, and survivorship data were collected from medical records for patients with a minimum of two years of follow-up. Primary outcomes included overall implant survivorship at two years as well as aseptic survivorship, revision rates of the DM acetabular shell, and average time to revision. Patient-reported outcomes were collected in the form of HOOS JR. RESULTS/UNASSIGNED:A total of 250 hips in 245 patients had a minimum two-year follow-up. Primary osteoarthritis (80%) was the most common indication for index THA. The average aseptic survivorship of the DM acetabular components at two years for the cohort was 98.4% and survivorship of the acetabular implants overall was 97.6%. There were a total of four (1.6%) aseptic revisions of the DM acetabular component. Reasons for aseptic acetabular revision included one case of instability, one intraprosthetic dislocation, one periprosthetic acetabular fracture, and one malpositioned acetabular cup resulting in impingement. The mean time of follow-up was 893.9 days. Eighty-seven patients had preoperative and two-year HOOS JR available. HOOS JR improved by an average of 38.5 points. CONCLUSION/UNASSIGNED:This novel DM acetabular implant demonstrates excellent survivorship at two years follow-up with low rates of instability and intraprosthetic dislocation and no episodes of metal-on-metal corrosion. Use of the DM implant demonstrated clinically relevant improvements in patient-reported outcomes at two years.
PMCID:10805547
PMID: 38264013
ISSN: 2090-3464
CID: 5624932
Indications, Clinical Outcomes, and Re-Revisions Following Revision Total Hip Arthroplasty - Does Age Matter?
Lawrence, Kyle W; Raymond, Hayley E; Sicat, Chelsea S; Roof, Mackenzie A; Arshi, Armin; Rozell, Joshua C; Schwarzkopf, Ran
BACKGROUND:Younger age is associated with increased revision incidence following primary total hip arthroplasty, though the association between age and repeat revision following revision total hip arthroplasty (rTHA) has not been described. This study aimed to describe the incidences and indications for subsequent revision (re-revision) following rTHA based on age. METHODS:Patients undergoing aseptic rTHA from 2011 to 2021 with minimum 1-year follow-up were retrospectively reviewed. Patients were stratified into 3 groups based on age at the time of index rTHA (ie, <55 years, 55 to 74 years, and >74 years). Perioperative characteristics, complications, and re-revisions were compared between groups. RESULTS:Of 694 included rTHAs, those in the >74 age group were more likely to undergo rTHA for periprosthetic fracture (P < .001) while those in the <55 age group were more likely to undergo rTHA for metallosis/taper corrosion (P = .028). Readmissions (P = .759) and emergency department visits (P = .498) within 90 days were comparable across ages. Rates of re-revision were comparable at 90 days (P = .495), 1 year (P = .443), and 2 years (P = .204). Kaplan-Meier analysis of all-cause re-revision at latest follow-up showed a nonstatistically significant trend toward increasing re-revisions in the <55 and 55 to 74 age groups. Using logistic regressions, smoking and index rTHA for instability were independently associated with re-revision, while age at index surgery was not. CONCLUSIONS:While indications for rTHA differ across age groups, rates of 2-year re-revision are statistically comparable between groups. Further studies are warranted to understand the association between age, activity, and re-revision rates after 5 years postoperatively.
PMID: 37879423
ISSN: 1532-8406
CID: 5620442
Precision or Pitfall? Evaluating the Accuracy of ICD-10 Coding for Cemented Total Hip Arthroplasty: A Multicenter Study
Singh, Vivek; Jolissaint, Josef E; Kohler, James G; Goh, Megan; Chen, Antonia F; Bedard, Nicholas A; Springer, Bryan D; Schwarzkopf, Ran
BACKGROUND:The International Statistical Classification of Diseases and Related Health Problems, 10th Revision, Procedure Coding System (ICD-10-PCS) was adopted in the U.S. in 2015. Proponents of the ICD-10-PCS have stated that its granularity allows for a more accurate representation of the types of procedures performed by including laterality, joint designation, and more detailed procedural data. However, other researchers have expressed concern that the increased number of codes adds further complexity that leads to inaccurate and inconsistent coding, rendering registry and research data based on ICD-10-PCS codes invalid and inaccurate. We aimed to determine the accuracy of the ICD-10-PCS for identifying cemented fixation in primary total hip arthroplasty (THA). METHODS:We retrospectively reviewed all cemented primary THAs performed at 4 geographically diverse, academic medical centers between October 2015 and October 2020. Cemented fixation was identified from the ICD-10-PCS coding for each procedure. The accuracy of an ICD-10-PCS code relative to the surgical record was determined by postoperative radiograph and chart review, and cross-referencing with institution-level coding published by the American Joint Replacement Registry (AJRR) was also performed. RESULTS:A total of 552 cemented THA cases were identified within the study period, of which 452 (81.9%) were correctly coded as cemented with the ICD-10-PCS. The proportion of cases that were correctly coded was 187 of 260 (72%) at Institution A, 158 of 185 (85%) at Institution B, 35 of 35 (100%) at Institution C, and 72 of 72 (100%) at Institution D. Of the 480 identified cemented THA cases at 3 of the 4 institutions, 403 (84%) were correctly reported as cemented to the AJRR (Institution A, 185 of 260 cases [71%]; Institution B, 185 of 185 [100%]; and Institution C, 33 of 35 [94%]). Lastly, of these 480 identified cemented THA cases, 317 (66%) were both correctly coded with the ICD-10-PCS and correctly reported as cemented to the AJRR. CONCLUSIONS:Our findings revealed existing discrepancies within multiple institutional data sets, which may lead to inaccurate reporting by the AJRR and other registries that rely on ICD-10-PCS coding. Caution should be exercised when utilizing ICD-10 procedural data to evaluate specific details from administrative claims databases as these inaccuracies present inherent challenges to data validity and interpretation.
PMID: 37973050
ISSN: 1535-1386
CID: 5610432
Treatment of Intraoperative Trochanteric Fractures During Primary and Revision Total Hip Arthroplasty
Habibi, Akram A; Schwarzkopf, Ran
Intraoperative trochanteric fractures during primary and revision total hip arthroplasty typically occur during femoral canal preparation and component placement. Several fixation strategies, including wires, cables, cable grips, and plating, are available for fracture fixation. Surgeons should consider patient activity level preoperatively, bone mineral density, and fracture morphology when deciding on fixation strategies. Patient activity must be modified postoperatively to prevent fracture displacement and additional complications. Patients must be counseled postoperatively about the possibility of decreased clinical outcomes.
PMID: 37980100
ISSN: 1558-1373
CID: 5608202
Role of femoral head material on readmission and mortality rates following elective primary total hip arthroplasty in Medicare patients
Sicat, Chelsea Sue; Singh, Vivek; Muthusamy, Nishanth; Spano, Paul J; Nezwek, Trevor A; Huynh, Kevin; Schwarzkopf, Ran
INTRODUCTION/BACKGROUND:The role of different femoral head materials for total hip arthroplasty (THA) has been widely studied in the context of wear properties and corrosion. Cobalt chrome (CoCr) femoral heads are commonly used as a standard of comparison to other materials such as ceramic and oxidized zirconium (OxZi). This study aims to evaluate the impact of femoral head material on clinical outcomes in elective primary THA patients. METHODS:Retrospective analysis of THA patients within the Medicare claims database between October 2017 and September 2020 using diagnosis-related group codes was conducted. Information collected included sex, age, Charlson Comorbidity Index, and femoral head type. Patients with CoCr femoral heads were compared against patients with either OxZi or ceramic femoral heads using 1:1 propensity score matching. Z-testing and Chi-square analysis were used to determine between-group significance. RESULTS:In total, 112,960 elective THA patients were included, with 56,480 in OxZi or ceramic and 56,480 in CoCr. Readmission rates were lower in patients that received OxZi or ceramic femoral heads at 30-day (p < 0.0001), 60-day (p < 0.0001), and 90-day postoperatively (p < 0.0001) compared to CoCr. Mortality rates were also lower in patients that received OxZi or ceramic femoral heads at 30-day (p = 0.004), 60-day (p = 0.018), and 90-day postoperatively (p = 0.009) compared to CoCr. CONCLUSION/CONCLUSIONS:CoCr femoral heads had higher rates of readmissions and mortality compared to OxZi or ceramic. Further analysis of bearing surface combinations and sub-group analyses to determine significance between-group differences is needed. LEVEL III EVIDENCE/METHODS:Retrospective analysis.
PMID: 37615684
ISSN: 1434-3916
CID: 5599322
Opioid Consumption and Mobilization in Staged Bilateral Total Joint Arthroplasty: Did We Learn Our Lesson the First Time?
Bieganowski, Thomas; Kugelman, David N; Feng, James E; Schwarzkopf, Ran; Rozell, Joshua C
BACKGROUND:In patients who require bilateral total hip arthroplasty (THA) or total knee arthroplasty (TKA), staged procedures are a reasonable option for treatment of bilateral osteoarthritis. We sought to determine whether perioperative outcomes differed between first and second total joint arthroplasty (TJA). METHODS:This was a retrospective review of all patients who underwent staged, bilateral THA or TKA between January 30, 2017, and April 8, 2021. All patients who were included underwent their second procedure within 1 year of the first. Patients were separated based on whether both their procedures took place before or subsequently after an institution-wide opioid-sparing protocol that was implemented on October 1, 2018. A total of 961 patients who underwent 1,922 procedures met the inclusion criteria for this study. For THA, 388 unique patients comprised 776 procedures, while 573 unique patients comprised 1,146 TKAs. Opioid prescriptions were prospectively documented on nursing opioid administration flowsheets and converted to morphine milligram equivalents (MME) for comparison. Activity measure scores for postacute care (AM-PAC) were used as a measurement of physical therapy progression. RESULTS:Hospital stays, home discharges, perioperative opioid usages, pain scores, and AM-PAC scores were not significantly different for the second THA or TKA compared to first procedure, regardless of timing in relation to the opioid-sparing protocol. CONCLUSION/CONCLUSIONS:Patients experienced similar outcomes following their first versus their second TJA. Limited opioid prescriptions following TJA do not negatively impact pain and functional outcomes. These protocols can safely be instituted to help mitigate the opioid epidemic. LEVEL III EVIDENCE/METHODS:Retrospective Cohort Study.
PMID: 37331439
ISSN: 1532-8406
CID: 5542482
Does the Primary Surgical Approach Matter when Choosing the Approach for Revision Total Hip Arthroplasty?
Christensen, Thomas H; Humphrey, Tyler J; Salimy, Mehdi S; Roundy, Robert; Goel, Rahul K; Guild, George N; Schwarzkopf, Ran; Bedair, Hany S; Aggarwal, Vinay K
INTRODUCTION/BACKGROUND:Multiple surgical approaches are used for primary total hip arthroplasty (pTHA) and revision total hip arthroplasty (rTHA). This study sought to investigate prevalence of discordance of pTHA and rTHA surgical approaches and to evaluate the impact of approach concordance on postoperative outcomes. METHODS:A multi-center retrospective review of patients who underwent rTHA from 2000 to 2021 was conducted at three large, urban academic centers. Patients who had a minimum one-year follow-up post-rTHA were included and grouped based on whether they received pTHA via a posterior (PA), direct anterior (DA), or laterally-based (DL) approach, and by concordance of index rTHA approach with their pTHA approach. Of the 917 patients studied, 839 (91.5%) were included in the concordant cohort and 78 (8.5%) in the discordant cohort. Patient demographics, operative characteristics, and postoperative outcomes were compared. RESULTS:Discordance was most prevalent in the DA-pTHA subset (29.5%), compared to the DL-pTHA subset (14.7%) or PA-pTHA subset (3.7%). Discordance varied significantly between primary approaches among all revisions, with DA-pTHA patients having the highest discordance rate for patients revised for aseptic loosening (46.3%, P<0.001), fracture (22.2%, P<0.001), and dislocation (33.3%, P<0.001). There were no differences between groups in dislocation rate, re-revision for infection, or re-revision for fracture. CONCLUSION/CONCLUSIONS:The results of this multicenter study showed patients who received pTHA via the DA were more likely to receive rTHA via a discordant approach compared to other primary approaches. Since approach concordance did not impact dislocation, infection, or fracture rates after rTHA, surgeons can feel reassured using a separate approach for rTHA.
PMID: 37393962
ISSN: 1532-8406
CID: 5538902
Clinical Outcomes of Offset Stem Couplers with or without Cone Augmentation in Revision Total Knee Arthroplasty
Fiedler, Benjamin; Bieganowski, Thomas; Singh, Vivek; Marwin, Scott; Rozell, Joshua C; Schwarzkopf, Ran
Intramedullary stems are often required in patients undergoing revision total knee arthroplasty (rTKA) to achieve stable fixation. Significant bone loss may require the addition of a metal cone to maximize fixation and osteointegration. The purpose of this study was to investigate clinical outcomes in rTKA using different fixation techniques. We conducted a single-institution retrospective review of all patients who received a tibial and femoral stem during rTKA between August 2011 and July 2021. Patients were separated into three cohorts based on fixation construct: press-fit stem with an offset coupler (OS), fully cemented straight (CS) stem, and press-fit straight (PFS) stem. A subanalysis of patients who received tibial cone augmentation was also conducted. A total of 358 patients who underwent rTKA were included in this study, of which 102 (28.5%) had a minimum 2-year follow-up and 25 (7.0%) had a minimum 5-year follow-up. In the primary analysis, 194 patients were included in the OS cohort, 72 in the CS cohort, and 92 in the PFS cohort. When stem type alone was considered, there was no significant difference in rerevision rate (p = 0.431) between cohorts. Subanalysis of patients who received augmentation with a tibial cone demonstrated that OS implants led to significantly higher rates of rerevision compared with the other two stem types (OS: 18.2% vs. CS: 2.1% vs. PFS: 11.1%; p = 0.037). The findings of the present analysis demonstrate that CS and cones in rTKA may provide more reliable long-term outcomes compared with press-fit stems with OS. LEVEL III EVIDENCE: Retrospective Cohort Study.
PMID: 37142239
ISSN: 1938-2480
CID: 5509132
An Analysis of Component Positioning, Offset, and Limb Length Restoration in Computer-Assisted Hip Resurfacing Arthroplasty
Schoof, Lauren H; Luthringer, Tyler A; Gualtieri, Anthony; Gabor, Jonathan A; Novikov, David; Schwarzkopf, Ran; Marwin, Scott
INTRODUCTION/BACKGROUND:Hip resurfacing arthroplasty (HRA) is a surgical option with positive outcomes at medium-term follow-up for young, active patients with osteoarthritis. However, early failures of HRA often occur due to improper implant placement. The purpose of this study was to assess the utility of computer-assisted navigation in the effort to optimize implant positioning following HRA. MATERIALS AND METHODS/METHODS:A retrospective analysis of 262 consecutive HRAs at a single institution was performed. Radiographic analysis included measurements of cup inclination and anteversion, leg length restoration (LLR), and offset. Cup position was evaluated based on placement within Lewinnek parameters and the surgeon's preferred anteversion (10° to 20°). Chi-squared and unpaired Student's t-test were performed for all categorical and continuous variables, respectively. RESULTS:One hundred fifty-six cases were performed using conventional technique and 106 cases used computernavigation. Computer-assisted HRA (caHRA) had a longer mean surgical time (129 vs. 110 minutes; p < 0.001) but shorter average LOS (1.1 vs. 1.5 days; p < 0.001). Cup position was within the surgeon-preferred target zone in 47% of caHRA versus 22% of conventional HRA (p = 0.0001). Cup position fell within the Lewinnek safe zone in 86% of caHRA versus 60% of conventional HRA (p < 0.001). Global offset was reduced by a mean of 6.4 mm in caHRA versus 8.4 mm (p = 0.036). No differences in rates of complication (p = 0.406), reoperation (p = 1.00), or 90-day readmission (p = 0.568) were observed. CONCLUSION/CONCLUSIONS:Computer-assisted technology in HRA allows for comparable clinical outcomes to conventional technique. Cup position accuracy and precision is improved by computer navigation in HRA.
PMID: 37639346
ISSN: 2328-5273
CID: 5923232