Citations

Abstract Introduction Younger, more active patients increasingly undergo total hip arthroplasty (THA) and commonly inquire about expectations and timeline regarding return to sport (RTS) and exercise. The direct anterior approach (DAA) may facilitate faster recovery and decreased instability risk, but long-term RTS data are limited. Methods A retrospective registry review identified all primary DAA THAs from 2010 and 2020. Patients who had less than five-year follow-up were excluded. Eligible patients completed a survey on preoperative and postoperative sport participation, time to RTS, and potential factors limiting RTS. A total of 886 patients (466 women and 428 men) responded to the survey. Their mean age was 62.8 years (range, 28 to 93), and their mean body mass index was 29.0 (range, 17 to 49). Results In the year prior to THA, 84% walked, 31% hiked, 27% cycled, and 11% ran. Postoperatively, 74% returned fully to prior activities and 16% returned with modifications, with 90% of these patients achieving RTS within one year. High-impact sport participation decreased from 24% preoperatively to 10% postoperatively, and running decreased from 11 to 5% (P < 0.001). Those who discontinued running most commonly cited surgeon advice (34%), fear of damaging the joint (21%), and pain (20%) as contributing factors for running cessation. Overall rates of revision were 4.5% for the running cohort and 3.2% for the non-running cohort (P = 0.651). Conclusion At a minimum five-year follow-up, most patients who underwent DAA THA successfully returned to sporting activities, typically within six months postoperatively. The majority resumed low-impact sports, while participation in high-impact activities declined. Patient counseling and fear of joint damage was a common reason for avoiding return to sport, despite mixed evidence suggesting increased risks of arthroplasty failure with high-level activities. Future prospective studies are warranted to better guide postoperative activity recommendations and clarify the long-term implications of sport participation after THA.

Abstract Background Femoral exposure is among the most challenging aspects of total hip arthroplasty (THA) through a direct anterior approach (DAA). Soft tissue releases are performed to improve exposure, although the contribution of each structure to femoral mobility is not well quantified to date. The purpose of this study was to quantify release-related femoral displacement during DAA THA. Methods Eight hips from cadaveric specimens underwent a DAA. A mechanical testing device applied 110N of anterior distraction force through a hook inserted into the proximal femur. Displacement was recorded in triplicate at baseline and after each sequential release: inferomedial capsule (A), superior capsule (B), obturator internus for left hips (C1) or piriformis for right hips (C2), piriformis for left hips (D1) or obturator internus for right hips (D2), obturator externus (E), quadratus femoris (F), tensor facia lata (G), sartorius (H), and direct head of the rectus femoris (I). Results Baseline anterior femoral mobility measured 31.7±10.1mm and changed minimally after inferomedial (30.2±9.7mm) and superior capsular release (32.8±11.1mm). Larger increases occurred with the isolated addition of obturator internus (+18.8mm, p=0.065) or piriformis (+9.5mm, p=0.024) release. Greater additional anterior femoral mobility resulted from subsequent piriformis (+41.0mm, p=0.001) or obturator internus release (+27.2mm p=0.010). Additional releases demonstrated progressively increasing anterior displacement. Conclusion Femoral exposure can be challenging and may require varying degrees of soft tissue release. This biomechanical model quantifies the displacement achieved with each sequential release through extensive mobilization and provides objective reference values to guide surgeons in obtaining safe and adequate femoral exposure.

ABSTRACT We characterize copine‐4 (CPNE4)‐IgG and report clinical associations. Among 844 samples with unclassified neural IgGs identified by mouse‐brain indirect immunofluorescence assay over 2 years, 5 samples (serum, 3; CSF, 2) from 3 patients produced a distinctive cerebrum‐restricted synaptic pattern. Protein microarray disclosed CPNE4 “top hit” in those 3 patients; specificity was confirmed by 3 CPNE4‐specific assays (confocal IFA, cell‐based, and western blot). Median onset age was 67 years (range 60–68); all had encephalitis: a brainstem syndrome during immune checkpoint inhibitor therapy for lung cancer (2) and anti‐NMDA‐receptor encephalitis accompanied by neuroectoderm‐lineage cancer (1). To date, CPNE4‐IgG has paraneoplastic encephalitis significance.

Background Propionic acidemia (PA) is a rare inborn error of metabolism that typically presents in infancy; however, late-onset variants may manifest with atypical features, including cardiac involvement. Dilated cardiomyopathy (DCM) is an uncommon but serious complication. Case summary A 15-year-old with no prior medical history but a significant maternal family history of cardiomyopathy of unknown etiology from an Amish background presented with altered mental status, increased work of breathing, and progressive edema in the context of preceding viral illness. Evaluation revealed severe biventricular dysfunction, chamber dilation, and findings consistent with chronic DCM. Despite supportive management, her course was complicated by ventricular arrhythmias and clinical deterioration. Metabolic workup demonstrated elevated propionylcarnitine and increased urinary 2-methylcitric acid, confirming late-onset variant PA. She was treated with intravenous carnitine and a specialized metabolic formula; however, cardiac function remained severely impaired. In accordance with family wishes, she was discharged home on hospice care. Conclusion Late-onset PA can present as isolated cardiomyopathy in adolescence. Early consideration of metabolic etiologies is essential in unexplained DCM, particularly in high-risk populations.

Abstract Background Detecting Histoplasma (HP) and Blastomyces (BM) antigen (Ag) in urine (U) and serum (S) is an essential diagnostic tool for these pathogens. Labs have added bronchoalveolar lavage (BAL) and cerebrospinal fluid (CSF) as additional HP and BM Ag testing sources. We evaluated the sensitivity of Ag detection in U and S in patients with detected HP or BM Ag in BAL or CSF by enzyme immunoassay (EIA). Methods 14 patients with HP or BM Ag-positive results made up the CSF cohort. The Ag concentrations were below the limit of quantification (< LoQ, N=3), above the limit of quantification (> LoQ, N=1), and 0.3 to 9.5 ng/mL (mean = 2.3 ng/mL, N=10). The BM Ag-positive in BAL group included 24 patients, with concentrations of LoQ (N=5), and 0.3 to 11.3 ng/mL (mean = 3.5 ng/mL, N=15). HP Ag-positive in BAL comprised 36 patients, with 3 LoQ, and 23 ranging from 0.8 to 16.9 ng/mL (mean = 4.7 ng/mL). All patients were checked for routine clinical HP and BM EIA Ag test results on U and S. HP BAL patients were also investigated for cross-reacting galactomannan (GM; Aspergillus EIA in S or BAL) and (1?3)-ß-d-glucan (BDG; Fungitell EIA in S) antigen test orders. Test results greater than 14 days before or after CSF or BAL Ag testing were excluded. Results 100% (14/14), 95.7% (22/23), and 83.3% (30/36) of HP/BM CSF, BM BAL, and HP BAL Ag-positive patients were also positive in U and/or S, when both additional sources were ordered, respectively. Of the 6 HP BAL patients without positive U or S results, 3 had GM and BDG testing performed. All 3 had high signal GM and/or BDG results in S and/or BAL. In conjunction with low HP Ag levels in BAL (1.0 to 1.53), these findings suggest cross-reactivity in the HP BAL Ag test. Classifying these 3 patients as HP BAL false-positive shows a positive agreement of 90.9% (30/33) between HP BAL and HP U/S. Conclusion 16 patients in the BAL cohorts were Ag-positive for HP and BM, demonstrating the inability to discriminate between these dimorphic fungi through Ag testing. HP/BM CSF Ag testing showed no increase in sensitivity when U/S were tested. Minimal increases in sensitivity were observed in BM/HP BAL versus U/S. However, false-positive results in BAL due to cross-reactivity with GM/BDG cannot be ruled out, suggesting limited utility in the invasive CSF/BAL sources.

Abstract Background A strong continuous improvement culture within a clinical laboratory is critical for quality improvement (QI) and patient safety. Broad staff buy-in is essential for successful QI and error reduction. To foster this, the Central Clinical Laboratory at Mayo Clinic (Rochester, MN) instituted a medical director-initiated recognition program to encourage and reward staff for identifying QI opportunities or detecting errors impacting patient testing (good catches, GC). This study aimed to assess the 4-year impact of this recognition program, which encourages submission, peer review and public or anonymous acknowledgment of QI ideas and GCs, within a high-volume, automated clinical laboratory. Methods All GC and QI submissions were reviewed and tracked for 4 years (Jan 2022-Dec 2025). Annual submissions and individuals awarded were quantified. All GC submissions were evaluated through the laboratory’s event review process. QI idea submissions were initially reviewed by a team to determine eligibility and awards were given anonymously or publicly at staff meetings based on awardee preference. QI projects were categorized by testing phase/area involved and project status (complete, in progress, not implemented) as of February 1, 2026. Completed QI projects were further categorized by project type (Just Do It versus structured QI), testing phase/area and whether the QI project impacted patient care, laboratory operations/efficiency or clinical laboratory scientist safety. The mean and standard deviation (SD) timeframes from submission to review, acknowledgement and project completion were calculated. Results Over four years, 236 total awards were given for 219 submissions (some with multiple contributors), to 48 unique laboratory staff members. Submissions included 75 GC (n=34 unique individuals), 140 QI (n=38 unique individuals) and 4 GC+QI (n=4 unique individuals). There were 29, 36, 42 and 37 QI submissions for years 1-4, respectively. GC submission numbers in years 1-4 were 20, 26, 11, 22, respectively. All GCs proactively detected errors. The categories of QI project ideas submitted included 31(22%) pre-analytical, 40 (28%) analytical, 19 (13%) post-analytical, 36 (25%) communication/education and 18 (13%) work environment/support improvements. Of the QI submissions, 78 (54%) were implemented/completed, 49 (34%) remained in progress and 17 (12%) were not implemented. Completed QI projects included 34 (44%) Just Do It, 40 (51%) structured QI projects and 4 (5%) interdepartmental initiatives. The implemented QI projects consisted of 15 (19%) pre-analytic, 23 (29%) analytic, 11 (14%) post-analytic, 18 (23%) communication/education and 11 (14%) work environment/support improvements. Of the completed QI projects, 54 (69%) impacted laboratory operations/efficiency, 13 (17%) had patient care impact, 9 (12%) impacted both (patient care/efficiency) and 2 (3%) impacted staff safety. Average+/-SD timeframes (days) from submission were: 18+/-25 to initial review, 50+/-32 to staff acknowledgement and 113+/-141 to QI project implementation/completion. Conclusion The sustained engagement in QI idea submissions, coupled with a 54% implementation/completion rate, demonstrated the significant success of this recognition program in fostering a culture of continuous improvement. The GC component encouraged event reporting and rewards proactive error detection. This award program serves as a valuable model for promoting patient safety and operational efficiency in high-volume clinical laboratories.

Abstract Background Alternative assessment of performance (AAP) for specific immunological analytes is challenging due to biological and analytical variability. The main objective of this study was to evaluate performance of the laboratory AAP program for effectiveness and gaps. Methods A historical analysis of AAP for fifteen (n=14) specific immunology biomarkers from 2017 – 2021, averaging 64 challenges per year, was performed. The acceptance criteria defined for each analyte were based on the AAP result percentage difference from the target. Testing was categorized by methodology: enzyme-linked immunosorbent assay (ELISA), electrochemiluminescent immunoassay (ECL), fluoroenzyme immunoassay (FEIA) and multiplex immunoassay (MIA). The performance of each analyte was evaluated against established acceptance criteria; AAP failures were categorized based on the failed parameter. A review of each analyte’s inter-precision data was completed to demonstrate the performance of each analyte during initial validation. Following this evaluation, modified acceptance criteria were established, and an assessment of analyte performance for AAP was completed to determine impact. Results Current percent difference acceptability for testing ranged from 20% to 25% of target. AAP success rate was 99%. Major AAP failure categories were identified as AAP material, methodological, AAP evaluation, technical, analytical, or non-identifiable explanation after extensive troubleshooting. Review of each analyte’s inter-precision data varied between 2% to 22%. Following the evaluation, modifications were made to expand the percent difference acceptability from 20% to 30% of target for each analyte depending on their analytical performance. AAP success rate post modification was 98%. Conclusion Analysis of AAP performance pre and post AAP acceptance criteria modification showed no significant increase in AAP failures. Success rate remains stable. Modifications to acceptance criteria were made based on clinical impact of testing and to align with known analytical performance. Expanded acceptance criteria improved flexibility in reviewing of AAP acceptance and allowed for a comprehensive analysis of overall analyte performance.

Abstract Background Anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitis is characterized by proteinase 3 (PR3) and myeloperoxidase (MPO) antibodies. PR3-ANCA and MPO-ANCA result in cytoplasmic and perinuclear staining, respectively, on ethanol-fixed neutrophils. However, discrepancies between solid-phase and immunofluorescence testing for ANCAs do occur; in these cases, review by laboratory directors is required, sometimes resulting in requests for repeat or confirmatory testing. Consequences of inadequate communication leads to overdue test results and possibly test cancellation due to exceeded specimen stability. The purpose of this project was to improve communication in the ANCA review process, with the goal of decreasing personnel communication time and improving turn-around time for results. Methods The current process for management of ANCA test review involved an E-mail notification to laboratory directors that pending result required review; after assessing the results, lab directors would E-mail management team, who would communicate with laboratory staff that additional testing was needed. Results from additional testing was summarized in a spreadsheet that could be reviewed by lab directors. In the new process, laboratory directors are notified by E-mail that a pending ANCA test requires review; if additional testing is needed, a web-based form is completed by laboratory directors. These requests are cataloged in an on-line database, which triggers logic to automatically notify laboratory testing personnel (created in Microsoft Power Automate). After testing is completed, a second on-line form is submitted by testing personnel to catalog results. When all required testing is complete, an automatic E-mail notifies laboratory directors. Data was collected retrospectively on 418 discrepant ANCA results, documenting the time from medical director request to result reported, estimated time spent on communication, and the number of confirmatory tests per patient, for the 10 months preceding the database inauguration and for the 10 months after. Results A total of 171 requests for additional ANCA testing were requested by laboratory directors from 1/25/2024 through 12/2/2024 utilizing the manual E-mail process; a total of 247 similar requests were managed through the online database process from 12/4/2024 through 10/8/2025. The average time from request to reported result decreased from 3 hours 17 minutes on the E-mail method to 3 hours 1 minute on the database method, corresponding to an 18% reduction. The maximum time from request to reported result decreased by 48% (20 hours 22 minutes to 10 hours 22 minutes for the E-mail and database methods, respectively). The amount of communication time also decreased by 45% for laboratory directors (1074 to 303 minutes) and by 99% for laboratory management staff (339 to 3 minutes). The number of process deviations, such as cancellations due to stability and samples requiring additional manual communication, reduced by 45% (11 for E-mail method and 6 for database method). Conclusion Utilization of the new database had substantial improvements within the testing process, resulting in reduced communication time between laboratory personnel, decreased time from request to result report, and fewer deviations. By utilizing technology to execute routine tasks, the laboratory has improved its quality metrics while maintaining high level of care with improved employee satisfaction.

Abstract Background Nuclear magnetic resonance (NMR)–based lipoprotein analysis enables simultaneous quantification of lipoprotein particle concentration and size. Although primarily applied to cardiovascular disease (CVD) management, characteristic lipoprotein changes are also reported in patients with diabetes and chronic kidney disease (CKD). Both diseases are associated with increases in small low-density lipoprotein (sLDL), large very-low density lipoprotein (LVLDL), and decreased large high-density lipoprotein (LHDL). To elucidate this issue further, we aimed to evaluate NMR-measured lipoprotein size and particle concentrations in patients undergoing clinically ordered measured Iothalamate glomerular filtration rate (GFR) assessment, stratified by kidney function and diabetes status. Methods Lipoproteins were measured using Axinon software (numares AG, Regensburg, Germany) on a 600MHz Bruker NMR in residual clinical sera from patients undergoing iothalamate renal clearance (n=330). Reduced kidney function was defined as a measured GFR <60 mL/min/1.73m2. A lipoprotein insulin resistance (LPIR) score was calculated using LVLDL, sLDL, and LHDL particle concentrations and size using published methods (Otvos, et. al). Associations between lipoproteins and disease status were assessed using Wilcoxon rank-sum or Pearson’s chi-squared tests, as appropriate. Results Of 330 participants, 159 (48%) had reduced eGFR. No statistically significant differences in lipoprotein parameters were observed by kidney function. Participants with reduced GFR showed non-significant trends toward increased LVLDL, [median (IQR): 1.6(1.0-3.8) vs. 1.5(0.9-2.7) nmol/L; p =0.3], and decreased LHDL [3.4(1.1-7.2) vs. 4.3(1.7-6.4) mcmol/L; p=0.4]. No differences between patients with reduced GFR were observed for sLDL [436(280-604) vs. 455(286-631) nmol/L; p=0.5] or LPIR score [46(33-64) vs. 46(34-60; p=0.5]. Diabetes was diagnosed in 86 (26%) participants. Compared to non-diabetic participants, those with diabetes had significantly increased LVLDL [2.15(1.00-4.50) vs. 1.50(0.90-2.80) nmol/L; p=0.01], decreased LHDL [3.0(1.1-5.3) vs. 4.3(1.9-7.0) mcmol/L; p=0.04], and smaller LDL size [20.9(20.6-21.1) vs. 21.1(20.8-21.3) nm; p<0.001]. Despite increased sLDL in diabetes [462(324-655) vs. 443(273-612) nmol/L], the difference was not significant (p=0.3). The LPIR score was significantly higher among participants with diabetes [53(37-68) vs. 45(32-60); p<0.01]. Conclusion Our data support prior reports that diabetes is associated with adverse changes in lipoprotein particle size and concentration. In contrast, measured kidney function showed no significant independent association with NMR lipoprotein parameters in this cohort, nor does it skew diabetic evaluations. Our data suggests that the association between kidney function and lipoprotein patterns is not robust and may in part be caused due to diabetic related changes. Irrespective of eGFR, LPIR was a predictor of incident diabetes.

Abstract Background Cancer antigens (CA) 15-3 and 27.29 are used in the clinical management of breast cancer patients. While generally concordant, results for CA 15-3 and CA 27.29 should not be used interchangeably. For serial monitoring, it is suggested to consistently use either CA 15-3 or CA 27.29. While there is no added value in performing both tests routinely, analysis of ordering practices from Mayo Clinic revealed these assays were consistently ordered concurrently. To promote appropriate test utilization and enhance patient care, the Mayo Clinic Laboratory and Pathology Stewardship Committee proposed a Laboratory Information Systems (LIS) intervention to help steer providers toward monitoring one of the cancer antigen tests rather than both. Methods A duplicate order check was built and implemented into the LIS. The alert fires when both CA biomarker tests are ordered at the same time on the same patient. The intervention is a soft stop that allows providers to discontinue one of the cancer antigen orders, continue with both, or close out of the alert with no action. Results The impact of the intervention was measured by comparing the monthly percentage of concurrent orders for CA 27.29 and CA 15-3 pre- and post-intervention and by evaluating provider actions on the LIS alert. The initial intervention went live in March of 2025. Monthly concurrent order percentages were compared before and after the intervention, revealing a slight impact on concurrent ordering percentages, which went from 24% to 20% (Figure 1). Provider actions in response to the alert were monitored and analyzed. The results showed that the workflow was stopped in 11% of cases, one of the concurrent orders was removed or discontinued in 12% of cases, and the alert was not acted upon in 77% of cases. To address the low impact and high ignore rate of the first intervention, a second soft stop was implemented in November 2025 that fires when providers bypass the first alert. Subsequent data was pulled and analyzed to determine the impact of this additional intervention which brought the monthly concurrent order average down slightly to 18%. Conclusion Duplicate CA 15-3 and CA 27.29 test orders represent a persistent challenge in laboratory utilization management. In the first initiative, an initial LIS provider alert was employed to curb redundant test orders. However, analysis revealed that the alert was frequently ignored with minimal effect on reducing concurrent ordering rates. The subsequent two-step alert system within the LIS represents a proactive step toward reducing duplicate CA 15-3 and CA 27.29 orders. Data will continue to be monitored to evaluate both intervention outcomes and provider compliance. Ongoing feedback mechanisms will support continuous assessment of the initiative's effectiveness, including the identification of potential alert fatigue. Future lab stewardship efforts should focus on measuring the sustained impact of dual-stop alerts, assessing whether additional stops yield diminishing returns or reach an optimal threshold for promoting appropriate test utilization. Extending this approach to other commonly duplicated tests could amplify system-wide stewardship, drive quality improvement, and support ongoing education for providers.