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49 citation(s) found for "Lu, Yining".

Capsular Contributions to Hip Joint Stability: Clinical Anatomy and Implications for Surgical Management
Lu, Yining, Cabarcas, Brandon , Ahmad, Rana A. , Kelly, John J., Lachman, Nirusha , Nho, Shane, Hevesi, Mario, Cabarcas, Brandon C. , Kelly, John J., Krych, Aaron J. , Hevesi, Mario

Mayo Clinic

Clinical Anatomy | July 4, 2026 | Volume: No volume available | Issue: No issue available | Pages: No page available

10.1002/ca.70182 | PMID 42400381 Get It

ABSTRACT The hip capsule is a dense, fibrous structure that plays a crucial role in providing hip stability. Its biomechanical function is tied to its complex anatomy, which includes the iliofemoral, pubofemoral, and ischiofemoral ligaments, along with the circumferential fibers of the zona orbicularis. Anatomic and biomechanical studies with advanced imaging and arthroscopic techniques have provided better understanding of the capsular morphology and its contribution to hip stability. Additionally, these studies provide insight into how capsulotomy and subsequent capsular management at the time of hip arthroscopy can potentially influence postoperative outcomes. Growing clinical evidence supports capsular preservation and repair at the time of primary hip arthroscopy and demonstrates the potential negative outcomes of capsular deficiency, such as pain, dysfunction, and instability. This review provides a comprehensive overview of the gross, arthroscopic, radiologic, and biomechanical anatomy of the hip capsule.
Association of patient complexity with information processing and usability of electronic health records among ICU providers: a multicenter study
Khairat, Saif , Morelli, Joseph G. , Yang, Shiyi , Li, Yining, Mohan, Deepika , Ratwani, Raj M, Apathy, Nate C., Boynton, Marcella H, Carson, Shannon S, Khairat, Saif , Morelli, Jennifer , Herasevich, Vitaly , Apathy, Nate C , Herasevich, Vitaly , Handzel, Robert M. , Ratwani, Raj M. , Boynton, Marcella H. , Carson, Shannon S.

Mayo Clinic

Journal of the American Medical Informatics Association | January 21, 2026 | Volume: 33 | Issue: 4 | Pages: 881-889

10.1093/jamia/ocag017 | PMID 41719162 Get It

Abstract Objective This study aimed to evaluate how differences in case complexity affect information-processing burden, as measured by eye-tracking, as well as the efficiency of electronic health record (EHR) use among healthcare providers in the intensive care unit. Materials and Methods This cross-sectional study recruited providers from 4 U.S. medical centers that use 2 prominent EHR systems (Epic and Oracle). After reporting demographic information, participants reviewed 2 complex cases and 2 standard cases in their institution’s EHR system and then responded to 5 questions about each case, yielding a performance score. Information-processing burden was assessed by measuring the number of eye fixations via eye-tracking software. The efficiency of EHR use was assessed by measuring the task completion time, number of mouse clicks per minute, number of EHR screens viewed, and performance score. Results Eighty-one providers were included for analysis. Providers exhibited significantly more eye fixations (P < .001) and longer task completion times (P < .001) for complex cases than for standard cases. There were also significantly fewer mouse clicks per minute during complex cases (P < .001). Reviewing a complex case first led to significantly more eye fixations (P = .015) and longer task completion times (P < .01) than when a standard case was presented first. Case complexity did not significantly affect performance scores or the number of EHR screens viewed. Discussion Higher case complexity was shown to be associated with greater information-processing burden and less efficient EHR use. These findings have implications for enhancing the efficiency of EHR use, thereby leading to improved clinical decision-making and patient safety. Furthermore, reviewing complex cases first led to a greater information-processing burden, suggesting that providers could benefit from “warming up” with standard cases before reviewing complex cases.
AAOS OrthoInfo provides more accessible information regarding femoroacetabular impingement than ChatGPT-4 while information accuracy is comparable
Sasaki, Jared , Hand, Catherine, Feroe, Aliya G. , McMaster, Brandon, Lu, Yining , Forsythe, Brian, Okoroha, Kelechi R. , Hassan, Mahad M. , Forsythe, Brian , Forsythe, Brian , Hand, Catherine , Ulrich, Marisa N.

Mayo Clinic

Journal of Hip Preservation Surgery | January 13, 2026 | Volume: No volume available | Issue: No issue available | Pages: No page available

10.1093/jhps/hnag001 Get It

Abstract As artificial intelligence (AI) Large Language Models (LLM) like ChatGPT become more common in healthcare, patients increasingly use them to find medical information. While ChatGPT may support health literacy, its readability and accuracy compared to established resources remain unclear. The purpose of this study is to evaluate ChatGPT-4 responses on femoroacetabular impingement (FAI) and its surgical management compared to AAOS OrthoInfo content. We hypothesize that ChatGPT may deliver medically accurate information, but its readability may fall short when compared to OrthoInfo. Nine questions based on the OrthoInfo FAI page were submitted to ChatGPT-4, with and without a readability prompt. Topics included anatomy, pathology, cause, symptoms, workup, imaging, treatment, role of hip arthroscopy, and outcomes. Readability was assessed using validated indices. Accuracy was independently rated using a 4-point scale. Statistical comparisons were made using t-tests and ANOVA (P < 0.01 threshold). OrthoInfo content had a mean reading grade level of 8.0 and a Flesch Reading Ease score of 60.7. Unprompted ChatGPT responses were significantly less readable (grade level 16.2; Flesch score 21.7; P < 0.001). Prompting for readability improved ChatGPT outputs (grade level 10.6; Flesch score 58.2), making them comparable to OrthoInfo (P < 0.09). Accuracy was high across all sources, though OrthoInfo's response on FAI causes scored slightly lower (3.5 versus 4.0; P < 0.46). ChatGPT provides accurate information on FAI. However, without prompting, its complexity may hinder patient understanding. Prompting for readability enables ChatGPT to match established resources like OrthoInfo. Tailored prompting is key to using LLM effectively in patient education and promoting health literacy.
High Rates of Return to American Football After Primary Hip Arthroscopy for Femoroacetabular Impingement: A 2-Year Minimum Follow-up
Kang, Louis , Okolo, Maxwell, Cleary, Emmett J., Lu, Yining , Iyer, Sanathan , Levy, Bruce A., Hevesi, Mario, Okoroha, Kelechi R. , Krych, Aaron J. , Hevesi, Mario , Lu, Yining , Hevesi, Mario , Krych, Aaron J , Kang, Louis S , Levy, Bruce A.

Mayo Clinic

Orthopaedic Journal of Sports Medicine | January 2, 2026 | Volume: 14 | Issue: 1 | Pages: No page available

10.1177/23259671251397513 | PMID 41488346 Get It

Background: Femoroacetabular impingement (FAI) is a common cause of hip pain in young, active athletes. American football players place high demands on the hip due to the sport's requirements for pivoting, cutting, and loading in deep flexion. Although arthroscopic treatment of FAI in professional National Football League (NFL) players has shown favorable outcomes, football-specific outcomes in non-NFL athletes remain limited. Purpose: To report the return-to-sport (RTS) rates and functional outcomes at a minimum 2-year follow-up for active American football players competing at multiple levels after primary hip arthroscopy for FAI. Study Design: Case series; Level of evidence, 4. Methods: An institutional database was queried to identify all active American football players who underwent primary hip arthroscopy with labral repair between 2010 and 2023. Demographic characteristics, radiographic parameters, procedure details, complications, and reoperations were collected. Follow-up was completed at a minimum of 2 years to obtain updated patient-reported outcome measures (PROMs) as well as football-specific data, including current participation and RTS status. PROMs were reported as mean ± standard deviation, and categorical variables, including RTS, were reported as frequencies. Pre- versus postoperative PROMs were compared using t tests or Mann-Whitney U tests to assess outcomes. Results: In total, 49 hips in 38 male football players (age, 18.1 years; range, 14-26 years) were included. Most athletes played at the high school (74%) or college level (21%). A total of 51% played as linemen. Labral repair was performed in all cases. At a mean 7.6 years, mean modified Harris Hip Score was 90 ± 13, Hip Outcome Score–Activities of Daily Living was 95 ± 7, and Hip Outcome Score–Sport was 89 ± 17. Overall mean surgery satisfaction was 8.7 ± 1.7 (out of 10). Significant postoperative improvements were observed in all PROMs ( P ≤ .002). Twelve players (32%) did not attempt RTS due to other nonmedical factors and were excluded from return to sport analysis. A total of 23 (88%) players achieved RTS, and 3 players (12%) did not. Two players (8%) cited other injuries, and 1 player (4%) continued to have hip limitations. Four hips (8%) underwent reoperation at a mean 4.9 years postoperative. Conclusion: Amateur American football players undergoing primary hip arthroscopy for FAI demonstrated excellent patient-reported outcomes and a high RTS rate of 88%, when excluding those who did not return for nonmedical reasons, at a mean 7.6-year follow-up. Notable positional differences were observed across multiple levels of play. Although outcomes were generally favorable, both medical and nonmedical factors could limit return to sport, particularly among high school and college athletes.
Efficacy and safety of pivekimab sunirine in combination with venetoclax plus azacitidine in unfit patients with newly diagnosed Acute Myeloid Leukemia
Burguera, Adolfo de la Fuente, Giannini, Maria Benedetta, Lunghi, Monia, Altman, Jessica K. , Walter, Roland B. , Begna, Kebede, Schliemann, Christoph , Sweet, Kendra , Wagstaff, Caroline, Pemmaraju, Naveen , Kantarjian, Hagop, Du, Yining , Potluri, Jalaja , Sallman, David A. , Walter, Roland B , Daver, Naval , Advani, Anjali S. , Montesinos, Pau , Garciaz, Sylvain , Wang, Eunice S. , Roboz, Gail J. , Curti, Antonio , Burke, Patrick W. , DeAngelo, Daniel J. , Platzbecker, Uwe , Vyas, Paresh , Wagstaff, Caroline

Mayo Clinic

Blood | December 4, 2025 | Volume: 146 | Issue: Supplement 1 | Pages: 651-651

10.1182/blood-2025-651 Get It

Abstract Introduction: While newly diagnosed patients (pts) with acute myeloid leukemia (AML) who are ineligible for intensive chemotherapy have prolonged survival outcomes with venetoclax plus azacitidine (VEN+AZA) over AZA alone (2-year overall survival rate: 37.5% vs 16.9%), more can be done to further enhance outcomes (Pratz et al., 2024). CD123 is overexpressed on AML blasts and leukemia stem cells in AML. Pivekimab sunirine (PVEK) is a first-in-class antibody-drug conjugate comprised of a high-affinity anti-CD123 antibody, a cleavable linker, and an indolinobenzodiazepine pseudodimer payload. Previously, in pts with CD123-positive AML, PVEK combined with VEN+AZA demonstrated robust response rates with a manageable safety profile (Daver et al., 2023). Here we report a subgroup analysis from a preliminary cohort of frontline (1L)-treated pts with AML. Methods: Data are from the dose expansion phase of an ongoing, open-label, multicenter, fully enrolled, Phase 1b/2 study of PVEK+VEN+AZA in adults with 1L unfit AML deemed CD123-positive by investigator. Unfit pts were aged ≥75 years (yr), or aged <75 yr with Eastern Cooperative Oncology Group performance status (ECOG PS) score 2–3, or ≥1 defined comorbidity. Pts received PVEK (0.045 mg/kg, intravenous [IV]) on Day (D) 7 plus VEN (400 mg equivalent, oral) daily in a 28-D cycle (cohort 1 received ≥14 D of VEN; cohort 2 received 28 D of VEN) plus AZA (up to 75 mg/m2, subcutaneous or IV) on D1–7. Bone marrow assessments were performed by D12–14 (cohort 1) or D18–21 (cohort 2) to determine VEN duration in cycle 1 and at the end of every subsequent cycle to assess responses and myelosuppression. The primary endpoint was antileukemia activity (complete remission [CR] rate) and measurable residual disease (MRD) assessments. Responses were determined using the modified European LeukemiaNet 2017 criteria (plus CR + partial hematologic recovery [CRh]). MRD-negativity was defined centrally as <0.1% using multiparameter flow cytometry. Safety was assessed as a secondary endpoint. Results: Among 1L unfit pts with CD123-positive AML (n=49), the median (range) age was 77 (58–85) yr, with most pts aged ≥75 yr (n=36 [74%]). Forty-two (86%) pts reported an ECOG PS ≤1, 14% (n=7) had secondary AML, and 20% (n=10) and 51% (n=25) had intermediate or adverse cytogenetic risk, respectively; 65% (n=32) and 35% (n=17) were reported as TP53wt or TP53mut, respectively. Eight (16%) pts bridged to stem cell transplant. The median (range) number of treatment cycles and duration of treatment were 4 (1–20) and 5.5 (0.7–22.7) months (mo), respectively, for PVEK; 4 (1–20) and 5.1 (0.9–22.9) mo for VEN; and 4 (1–21) and 5.7 (0.9–23.4) mo for AZA. For cohort 1 (n=10), the median (range) duration of VEN was 4.5 (2.1–22.9) mo, and for cohort 2 (n=39), the median (range) duration of VEN was 5.7 (0.9–15.2) mo. With a median (range) follow-up of 10 (1.2–26.7) mo, 63.3% (95% CI: 48.3%–76.6%) of pts achieved CR, 79.6% (95% CI: 65.7%–89.8%) achieved CR/CR with incomplete hematologic recovery (CRi), and 73.5% (95% CI: 58.9%–85.1%) achieved CR/CRh; morphologic leukemia free state was achieved in 4% (n=2) of pts. Of pts who achieved CR or CR/CRi with a MRD-evaluable sample, 92% (23/25) and 90% (27/30) achieved flow cytometry MRD-negativity (<0.1%) respectively. The most common (≥50% of pts) any grade treatment-emergent adverse events (AEs) were neutropenia/neutrophil count decreased and thrombocytopenia/platelet count decreased (both 69%); constipation (61%); and peripheral edema (51%). Three pts (6%) experienced AEs leading to discontinuation (myocardial infarction/soft tissue infection/thrombocytopenia) and 2 pts had AEs leading to death (respiratory failure/pancytopenia). Conclusions: Unfit pts with newly diagnosed CD123-postive AML demonstrated high CR rates with PVEK+VEN+AZA. These robust response rates were observed across the select mutational profiles tested. Follow up with duration of response and survival estimates among all pts, by molecular subgroups and MRD negativity status, are being evaluated. Triplet therapy in unfit 1L pts with CD-123–positive AML was well-tolerated, and no new safety signals were observed. These data highlight the need to further evaluate this regimen in a randomized trial.
327 Personalized neoepitope mRNA-based dendritic cell therapies against breast cancer
Henry, Skylar J.W. , Zhang, Yining , Kaushik, Akshansh, Pockaj, Barbara A. , Gustafson, Michael P. , Anderson, Karen S. , Batalini, Felipe , Roy, Olivia, Park, Jin G.

Mayo Clinic

Regular and Young Investigator Award Abstracts | November 5, 2025 | Volume: No volume available | Issue: No issue available | Pages: A374-A374

10.1136/jitc-2025-sitc2025.0327 Get It

Establishing Clinically Distinct Patient Treatment Subgroups Following Anterior Cruciate Ligament Reconstruction: A Machine Learning Clustering Analysis
Lu, Yining , Kang, Louis , Mavrommatis, Sophia , Hevesi, Mario , Okoroha, Kelechi R. , Saris, Daniël B.F. , Krych, Aaron J. , Tagliero, Adam J. , Camp, Christopher L. , Tagliero, Adam , Lu, Yining , Krych, Aaron J , Hevesi, Mario , Kang, Louis S , Saris, Daniël B.F.

Mayo Clinic

The American Journal of Sports Medicine | August 15, 2025 | Volume: 53 | Issue: 11 | Pages: 2542-2552

10.1177/03635465251360240 | PMID 40815848 Get It

Background: Treatment decisions in patients with anterior cruciate ligament (ACL) injuries are influenced by multiple factors, such as the desire to return to sports or symptomatic instability. Identifying the differential treatment effect of ACL reconstruction (ACLR) compared with nonoperative management on a patient-specific level can inform surgical decision-making. Hypothesis: Unsupervised machine learning can identify distinct patient subgroups based on outcome achievement after ACL injury, and ACLR will exert a protective effect on the development of posttraumatic osteoarthritis (PTOA) over nonoperative management. Study Design: Cohort study; Level of evidence, 3. Methods: A longitudinal populational registry identified patients with ACL injuries from 1990 to 2016 with a minimum 7.5-year follow-up. An unsupervised random forest algorithm was utilized to develop and validate patient subgroups. Treatment effects of ACLR on outcomes were analyzed using a machine learning causal inference estimator. Patient subgroup membership was incorporated into a multivariable logistic regression to identify factors predictive of optimal outcomes. Results: A total of 923 patients (785 primary ACLR, 138 nonoperative) were included. The random forest algorithm arrived at an optimal partition of 2 subgroups, with 653 patients in the optimal outcome subgroup (368 male [56.4%]; mean age, 26.0 ± 10.2 years; mean body mass index [BMI], 26.5 ± 4.30) and 270 patients in the suboptimal outcome subgroup (152 male [56.3%]; mean age, 35.0 ± 10.1 years; mean BMI, 30.5 ± 5.54). The latter group demonstrated significantly increased rates of secondary meniscal injury, development of symptomatic PTOA, and progression to total knee arthroplasty (TKA) at the final follow-up (all P < .01). In the optimal outcome subgroup, ACLR had significantly protective treatment effects on the risk of secondary meniscal injury (average treatment effect [ATE], 61%), contralateral ACL injury (ATE, 8%), symptomatic PTOA (ATE, 16%), and progression to TKA (ATE, 6%) (all P < .01). Conversely, in the suboptimal outcome subgroup, ACLR only protected against symptomatic PTOA (ATE, 11%) and progression to TKA (ATE, 8%) (both P < .01). Conclusion: Two clinically meaningful subgroups were identified from retrospectively collected data and found to experience differential treatment responses after ACL injuries. ACLR decreased the rate of development of PTOA and TKA in both subgroups but was not as effective in preventing secondary meniscal injuries or contralateral ACL injuries in patients who were older, heavier, or had concomitant medial meniscus injuries.
Defining Clinically Meaningful Subgroups in Patients Undergoing Arthroscopic Rotator Cuff Repair Using Unsupervised Machine Learning
Lu, Yining, Berlinberg, Elyse J. , Alder, Kareme D. , Chervonski, Ethan , Patel, Harsh, Rice, Morgan W. , Yanke, Adam B. , Cole, Brian J. , Verma, Nikhil N. , Hevesi, Mario , Alder, Kareme, Forsythe, Brian , Hevesi, Mario , Patel, Harsh H. , Forsythe, Brian

Mayo Clinic

Orthopaedic Journal of Sports Medicine | June 17, 2025 | Volume: 13 | Issue: 6 | Pages: No page available

10.1177/23259671251335977 | PMID 40535587 Get It

Background: Outcomes after arthroscopic rotator cuff repair (RCR) are frequently measured through clinically significant outcomes (CSOs) such as the minimal clinically important difference, the substantial clinical benefit, and the Patient Acceptable Symptom State. Global achievement of CSOs is challenging to predict. Purpose: To determine if unsupervised machine learning can identify distinct patient subgroups based on CSO achievement after elective arthroscopic RCR. Study Design: Case-control study; Level of evidence, 3. Methods: A prospectively collected database was analyzed to identify patients who underwent elective arthroscopic RCR from 2015 to 2017. Tear dimensions were measured on magnetic resonance imaging utilizing a validated technique. CSO achievements on the American Shoulder and Elbow Surgeons, the Single Assessment Numeric Evaluation, and the Constant-Murley subjective score at 2-year follow-up were calculated. An unsupervised random forest algorithm was utilized to develop and internally validate patient subgroups with significantly different rates of CSO achievement. Patient subgroup membership, along with a total of 30 demographic and clinical variables, as well as preoperative patient-reported outcomes, were incorporated into a stepwise multivariable logistic regression to identify factors predictive of optimal CSO achievement. Results: A total of 346 patients (192 male; mean ± SD age, 57.2 ± 9.1 years; body mass index, 30.1 ± 5.4 kg/m 2 ) were eligible for inclusion and followed for a mean of 3.8 years (range, 2.0-6.2 years) Of these, a total of 333 patients were partitioned by the random forest algorithm into 2 subgroups (stability, 0.16; connectivity: 180.8; Dunn: 0.16; silhouette: 0.05), with 176 patients in the optimal achievement subgroup and 157 patients in the suboptimal achievement subgroup. The 2 subgroups differed significantly (all P ≤ .004) in the likelihood of achievement of all CSOs. Stepwise multivariable logistic regression identified an increase of 1 mm in tear size in the sagittal dimension beyond 1.9 cm to predict a 10% increase in the probability of suboptimal achievement. Additional risk factors for suboptimal CSO achievement included increasing number of tendons involved (odds ratio [OR], 14.07; 95% CI, 4.50-44.02; P < .001), subscapularis involvement (OR, 8.67; 95% CI, 2.45-30.71; P = .01), and increased preoperative CMS score (OR, 1.11; 95% CI, 1.04-1.18; P = .001). Protective factors included performance of a subpectoral biceps tenodesis compared with biceps tenotomy (OR, 0.22; 95% CI, 0.05-0.92; P = .03). Conclusion: Clinically meaningful subgroups were uncovered using an unsupervised machine learning algorithm in patients undergoing arthroscopic RCR. Tear size, number of tendons involved, and subscapularis involvement were significant and additive predictors of suboptimal CSO achievement at 2-year minimum follow-up. Treatment of concurrent biceps pathology with tenodesis conferred 78% increased likelihood of CSO achievement compared with tenotomy.
Neuronal ABCA7 deficiency aggravates mitochondrial dysfunction and neurodegeneration in Alzheimer's disease
Wang, Ni , Pan, Yining , Starling, Skylar C , Haskell, Devon H., Quintero, Astrid, Kawatani, Keiji , Inoue, Yasuteru , Ma, Xiaoye, Aikawa, Tomonori , Martens, Yuka A. , Kurti, Aishe, Parsons, Tammee M., Perkerson, Ralph B., Ren, Yingxue , DeTure, Michael , Bao, Hanmei , Kanekiyo, Takahisa , Quintero, Astrid C, Shue, Francis , Roy, Bhaskar, Raulin, Ana‐Caroline , Dickson, Dennis W. , Han, Xianlin , Bu, Guojun

Mayo Clinic

Alzheimer's & Dementia | March 29, 2025 | Volume: 21 | Issue: 3 | Pages: No page available

10.1002/alz.70112 | PMID 40145325 Get It

Abstract INTRODUCTION Loss‐of‐function variants of the ABCA7 gene are associated with an increased risk of Alzheimer's disease (AD). How neuronal ABCA7 contributes to AD pathogenesis is unknown. METHODS Using neuron‐specific Abca7 KO mice (n Abca7 −/− ) with or without 5×FAD amyloid model background and post mortem AD brains, we investigated AD‐related phenotypes through comprehensive approaches including transcriptomics and lipidomics. RESULTS Lipidomics analysis detected altered lipid profiles in the brains and synaptosomes of 5×FAD; n Abca7 −/− mice compared to controls. Transcriptomics profiling revealed that neuronal ABCA7 deficiency altered the expression of genes and pathways related to mitochondrial homeostasis and apoptosis, particularly in excitatory neurons. Consistently, synaptosomes isolated from 5×FAD; n Abca7 −/− mice showed diminished mitochondria respiration and reduced synaptic protein levels, which is further supported by results from human AD brains. DISCUSSION Our findings reveal that neuronal ABCA7 plays a critical role in mitochondrial homeostasis important for neuronal function and survival in the presence of AD pathology. Highlights Neuronal ABCA7 deficiency exacerbates Aβ pathology and neuronal damage in 5×FAD mice. Neuronal ABCA7 deficiency alters brain transcriptomes and lipidomes of 5×FAD mice. Neuronal ABCA7 deficiency disturbs mitochondria functions in synaptosomes from 5×FAD mice. Neuronal ABCA7 expression associates with genes and pathways related to mitochondrial homeostasis in AD brains.
Posttraumatic Arthritis After Anterior Cruciate Ligament Injury: Machine Learning Comparison Between Surgery and Nonoperative Management
Lu, Yining , Jurgensmeier, Kevin , Lamba, Abhinav , Yang, Linjun , Hevesi, Mario , Krych, Aaron J. , Stuart, Michael J. , Camp, Christopher L. , Krych, Aaron J , Stuart, Michael J , Lu, Yining , Lamba, Abhinav , Hevesi, Mario , Jurgensmeier, Kevin , Yang, Linjun

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The American Journal of Sports Medicine | March 13, 2025 | Volume: 53 | Issue: 5 | Pages: 1050-1060

10.1177/03635465251322803 | PMID 40079334 Get It

Background: Nonoperative and operative management techniques after anterior cruciate ligament (ACL) injury are both appropriate treatment options for selected patients. However, the subsequent development of posttraumatic knee osteoarthritis (PTOA) remains an area of active study. Purpose: To compare the risk of PTOA between patients treated without surgery and with ACL reconstruction (ACLR) after primary ACL disruption using a machine learning causal inference model. Study Design: Cohort study; Level of evidence, 3. Methods: A geographic database identified patients undergoing ACLR between 1990 and 2016 with minimum 7.5-year follow-up. Variables collected include age, sex, body mass index, activity level, occupation, relevant comorbid diagnoses, radiographic findings, injury characteristics, and clinical course. Treatment effects of ACLR on the development of PTOA and progression to total knee arthroplasty (TKA) were analyzed with machine learning models (MLMs) in a causal inference estimator (targeted maximum likelihood estimation, TMLE), while controlling for confounders. Results: The study included 1194 patients with a minimum follow-up of 7.5 years, among whom 974 underwent primary reconstruction and 220 underwent nonoperative treatment. A total of 215 (22%) patients developed symptomatic PTOA in the ACLR group compared with 140 (64%) in the nonoperative treatment group ( P < .001), whereas 25 (3%) patients underwent TKA in the ACLR group compared with 50 (23%) in the nonoperative treatment group ( P < .001). Patients in the ACLR group had delayed TKA compared with patients in the nonoperative treatment group (193.4 vs 166.0 months, respectively; P = .02). TMLE evaluation revealed that reconstruction decreased the risk of PTOA by 11% (95% CI, 8%-13%; P < .001) compared with nonoperative treatment but did not demonstrate a significant effect on the rate of progression to TKA. Survival analysis with random forest algorithm demonstrated significant delay to the onset of PTOA as well as time to progression of TKA in patients undergoing ACLR. Additional risk factors for the development of PTOA, irrespective of treatment, included older age at injury, greater body mass index, total number of arthroscopic knee surgeries, and residual laxity at follow-up. Conclusion: MLMs in a causal inference estimator found ACLR to exert a significant treatment effect in reducing the rate of development of PTOA by 11% compared with nonoperative treatment. ACLR also delayed the onset of PTOA and progression to TKA.