Citations

Abstract Artificial intelligence (AI) encompasses the development of systems that can perform human‐like tasks, such as treatment guidance, decision‐making, pattern recognition and understanding language. Within AI, machine learning and deep learning play pivotal roles in diagnosis and outcome prediction, while natural language processing aids in synthesising large datasets from the electronic medical record. In orthopaedics, AI has demonstrated success in various areas, including image evaluation, surgical planning, outcome prediction, cohort identification and administrative tasks. The purpose of this manuscript was to provide an overview of the benefits of AI implementation within the field of orthopaedics. An additional goal was to address the challenges associated with producing high quality AI‐based research in a rapidly developing field. Level of Evidence Level IV.

Background: Immunotherapy-based regimens have expanded the treatment landscape for unresectable hepatocellular carcinoma (uHCC); however, real-world data are limited. Methods: This retrospective, observational study used data from electronic medical records from Mayo Clinic sites across the United States. Patients with uHCC who initiated a first-line (1L) systemic therapy between June 2020–October 2022 with ≥2 follow-up visits were included. Treatment patterns, overall survival (OS), and post-index gastrointestinal (GI) bleeding were assessed by GI bleeding risk defined by Child–Pugh Class B or C, pre-index GI bleeding, uncontrolled hypertension, or significant varices and band ligation. Results: Of 186 included patients, 68.8% had GI bleeding risk and 31.2% did not. Atezolizumab plus bevacizumab was the most common 1L systemic therapy in patients with or without GI bleeding risk (72.7% and 29.3%, respectively). Median OS (95% confidence interval) with atezolizumab plus bevacizumab was 12.8 (8.0–19.3) months and not reached in patients with and without GI bleeding risk, respectively. OS rates with atezolizumab plus bevacizumab in patients with or without GI bleeding risk, respectively, were 52.3% and 70.6% at 12 months, 41.6% and 57.8% at 18 months, and 34.6% and 51.3% at 24 months. Post-index GI bleeding with atezolizumab plus bevacizumab occurred in 19.4% and 5.9% of patients with and without GI bleeding risk, respectively. Conclusions: During this study period, atezolizumab + bevacizumab was the most common 1L therapy for patients with uHCC, regardless of GI bleeding risk. OS rates with atezolizumab + bevacizumab were lower in patients with versus without GI bleeding risk. Findings highlight the unmet need for guidance on characteristics-driven treatment decisions.

Background: The AFFINITY trial (NCT05890872) is a prospective, non-randomized, open-label, single-arm study evaluating the safety, immunological impact, and preliminary efficacy of Aliya pulsed electric field ablation in patients with solid tumors. Thirty-one patients were enrolled; thirty received lung lesion ablation prior to continuation on standard-of-care treatment. This manuscript reports six-month local control outcomes and immunological response characteristics. Radiological outcomes were assessed using a modified RECIST 1.1, and immunological impact was evaluated via changes in peripheral blood immunocyte populations and detection of immunoglobulins (Ig) to tumor-associated antigens in serum post-ablation. Methods: Twenty-eight patients underwent radiological assessment of ablated lesions at approximately 1-, 3-, and 6-month post-ablation to evaluate local control. Peripheral blood was collected for immune monitoring using flow cytometry and to detect IgG responses to biopsy-specific and tumor-associated antigens. Results: At 6 months, two cohorts emerged: 12 received ablation only, and 16 received ablation plus systemic and/or focal therapies (radiotherapy or second ablation). In the ablation-only group, imaging showed local control in all ablated lesions (8/12 SD, 4/12 PR), suggesting local efficacy without systemic therapy in those patients. Immunophenotyping showed dynamic changes in circulating immune cells, including T and B cell activation. A subset also exhibited modulation of tumor antigen-specific IgG, indicating a systemic humoral response. Conclusions: This analysis provides preliminary evidence that this form of ablation may promote local tumor control and modulate systemic immune function. These findings support the immunogenic potential of this specialized energy and warrant further investigation. Extended 12-month data for the full cohort will be reported in a future manuscript.

Background/Objectives: Chordoma, a rare slow-growing malignant bone tumor, remains therapeutically challenging due to its invasive nature. We examined institutional outcomes comparing imatinib and brachyury-directed vaccines. Methods: We used data from three sites of our quaternary care academic institution to analyze demographics, time to progression, overall survival, and adverse events in chordoma patients treated with imatinib or enrolled in a brachyury vaccine trial. Results: We included a total of 52 patients (8 in the brachyury vaccine cohort and 44 in the imatinib cohort) in the analysis. As expected, sacrococcygeal location was the most predominant in both cohorts: 62.5% in the brachyury cohort and 45.5% in the imatinib cohort. No demographic differences were present between the cohorts. ECOG was similar in both groups (p = 0.796). The primary outcome, time to progression (TTP), was shorter in the brachyury compared to the imatinib cohort (5.6 vs. 13 months, p = 0.0589), almost reaching statistical significance. Overall survival (OS) was comparable, 211 vs. 212 months for the brachyury and imatinib cohorts, respectively (p = 0.277). Although the brachyury vaccine cohort presented a higher incidence of adverse events than the imatinib cohort (75% vs. 31.8%, p = 0.021), the severity was milder. Conclusions: Imatinib showed longer disease control than the brachyury vaccine, though overall survival was similar. Future studies and deeper molecular insights are essential to develop better therapies and improve patient quality of life.

Background: Chronic Achilles tendon ruptures (CATRs) pose a clinical challenge because guidelines on optimal treatment modalities are lacking. This meta-analysis aims to investigate the use of Flexor Hallucis Longus (FHL) tendon transfer as a treatment option. Methods: A literature search was performed across multiple databases from inception until 31 July 2025. The databases searched included Ovid MEDLINE®, EMBASE (Elsevier), Cochrane Central Register of Controlled Trials and Cochrane Database of Systematic Reviews. Included studies presented CATR patients of all ages, with no previous surgeries to the ankle, who were managed with an FHL tendon transfer (PROSPERO ID: CRD42023489724). Results: Sixteen studies met the eligibility criteria with 323 patients. For functionality, baseline AOFAS-AH (American Orthopaedic Foot & Ankle Society—Ankle Hindfoot) scores were 56.85 (95% CI: 51.03–62.68, I2 = 96%). At ≥12 months post-operative follow-up, AOFAS-AH scores were 91.46 (95% CI: 88.45, 94.48, I2 = 93%). ATRS (Achilles Tendon Rupture Score) at baseline was reported as 31.04 (95% CI: 5.80, 56.28, I2 = 99%). At ≥12 months post-operative follow-up, ATRS amounted to 90.73 (95% CI: 83.69, 97.77, I2 = 89%). Overall complication rates were 7.5% (CI: 0.04,0.11, I2 = 40%), consisting of superficial infections at 4.2% (95% CI: 0.01, 0.07, I2 = 0%), activity limitations at 4% (95% CI: 0.01, 0.08, I2 = 0%) and disturbed wound healing at 3.8% (95% CI: 0.01, 0.06, I2 = 0%). The minimum clinically important difference (MCID) for ATRS was achieved at 12 months onwards. Conclusions: Surgical management of CATR patients with FHL tendon transfer appears to improve functionality and subjective outcomes, supporting its use amongst the treatment modalities available.

Introduction: Corticosteroid therapy has been demonstrated to improve prognosis and reduce mortality in patients with severe Coronavirus Disease 2019 (COVID-19) infection by attenuating the exaggerated inflammatory response that emerges in the late phase of infection. However, its impact on patients with pre-existing cardiovascular disease, who are at higher risk of complications, has not been specifically studied. The aim of this study is to evaluate the effect of corticosteroid therapy on mortality and long-term COVID-19 symptoms in this high-risk population. Methods: We analyzed the prospective registry HOPE-2. Patients with previous cardiovascular disease were selected, and 18-month all-cause death was defined as the primary endpoint. Long-term COVID-19 symptoms were considered as secondary endpoints. A total of 1188 patients with previous heart disease were included, of which 453 received corticosteroid treatment. Propensity score matching analysis in a 1:1 fashion was performed based on baseline variables that exhibited a p-value < 0.05 in the univariant analysis and outcome variables that defined corticosteroid use, with a final matched population of 796 patients. Results: In patients with pre-existing heart disease, corticosteroid treatment was not associated with differences in 18-month all-cause mortality (p = 0.52). However, a shorter duration of hospitalization (median: 8 days [IQR: 4–14] and 11 days [IQR: 7–18]; p < 0.001) was observed in patients who received corticosteroids. No significant differences in long-term COVID-19 symptoms were observed between the two groups. Conclusions: In patients with pre-existing heart disease, the absence of a clear harmful effect suggests that the positive effects of corticosteroids may be offset by their potential adverse effects which could contribute to the persistence of long COVID symptoms. This finding may reflect a differential response to corticosteroids in this high-risk subgroup, highlighting the need for further studies to clarify the role of this therapy in such patients.

Objective: Progressive apraxia of speech (PAOS) is a neurodegenerative syndrome characterized by impaired motor speech planning and programming, whereas behavioral variant frontotemporal dementia (bvFTD) is characterized by deviant behavioral (e.g., personality and social) features. Clinical and anatomic characteristics of bvFTD in the context of PAOS are understudied. Methods: We identified 12 participants with PAOS and features that were consistent with bvFTD at baseline or follow-up. Eleven completed a head MRI scan. We compared clinical features and anatomical patterns of atrophy in these 11 PAOS-bvFTD participants to 11 matched PAOS participants without bvFTD and 22 age- and sex-matched healthy controls. Statistical Parametric Mapping (SPM) was applied to visualize gray matter volume across both groups compared to controls and each other. Medians and 25th and 75th percentiles were assessed in patients and across groups; Fisher’s Exact Test and Mann–Whitney U tests were applied using BlueSky software, version 10.3.1-Pro. Results: As expected, PAOS-bvFTD participants performed worse on the Frontal Behavioral Inventory (median: 33/72 vs. 10/72), 20-item behavioral assessment scale (4.5/20 vs. 1.0/20), and the Neuropsychiatry inventory (4/36 vs. 1.5/36) compared to the PAOS group (p < 0.01 for all), with no differences in other demographic, neurological, or language tests. Seven of the eleven PAOS-bvFTD participants had bvFTD features develop within three years of symptom onset. The PAOS-bvFTD and PAOS groups showed volume loss in frontal lobe regions compared to controls, with PAOS-bvFTD participants having more prefrontal volume loss than PAOS participants. Conclusions: Behavioral features consistent with bvFTD can co-occur in patients with PAOS and are related to greater atrophy of the prefrontal cortex.

Purpose To compare clinical outcomes between augmented subchondral drilling (aSCD) and nonsubchondral drilling (NoSCD) techniques, both using a cartilage scaffold, in the treatment of isolated patellar cartilage lesions. Methods A retrospective cohort study was conducted on patients who underwent surgical treatment for isolated patellar cartilage using either an aSCD technique (a subchondral drilling augmented with a particulated cartilage allograft scaffold or a flexible osteochondral allograft scaffold) or a NoSCD technique (a particulated juvenile articular cartilage scaffold or a flexible osteochondral allograft scaffold implanted without performing a subchondral drilling). Patients were included if they had a minimum 2‐year follow‐up and excluded if they underwent concomitant meniscal or ligamentous procedures. While tibial tubercle osteotomy (TTO) was commonly performed, it was not a strict inclusion criterion. All procedures were performed through arthrotomy with a standardized postoperative rehabilitation protocol. Clinical outcomes included International Knee Documentation Committee (IKDC) and Lysholm scores, reoperation rates, conversion to total knee arthroplasty, and complications. Results A total of 65 knees were included: 31 in the aSCD group and 34 in the NoSCD group, with a mean follow‐up of 50.4 months (range, 24‐88 months). In the aSCD group, particulated allograft cartilage hydrated with platelet‐rich plasma was used in 80.7% of cases and flexible osteochondral allograft in 19.3%, while the NoSCD group was treated with Cartiform (Arthrex) in 70.6% and particulated juvenile articular cartilage in 29.4% of cases. TTO was performed in 87.0% of aSCD and 91.2% of NoSCD cases. Average defect sizes were 3.7 cm 2 (aSCD) and 4.0 cm 2 (NoSCD). At final follow‐up, the NoSCD group had significantly better outcomes, with higher median IKDC scores (81.0 vs 74.0; P < .001) and median Lysholm scores (83.0 vs 77.0; P < .001). A significantly greater proportion of NoSCD patients exceeded the minimal clinically important difference for IKDC (100% vs 80.6%; P = .024) but not for Lysholm (97.1% vs 93.5%; P = .935) at final follow‐up. In multivariable regression adjusting for scaffold type, TTO, and defect size, aSCD remained a significant independent predictor of lower final IKDC (β = –8.97; P = .001) and Lysholm (β = –12.71; P < .001) scores. The aSCD group had a significantly higher rate of repeat surgery (45.2% vs 14.7%; P = .015). There was no significant difference in conversion to total knee arthroplasty between groups ( P = .432). Conclusions For the treatment of isolated patellar cartilage lesions, a nonsubchondral drilling technique with scaffolding was associated with improved patient‐reported outcomes and fewer complications compared to a subchondral drilling technique with scaffolding, although there was no difference in the rate of conversion to total knee arthroplasty. Level of Evidence Level III, retrospective comparative study.

Abstract Purpose: AXL, a receptor tyrosine kinase related to oncogenic processes, is aberrantly expressed in various cancers and associated with treatment resistance. Enapotamab vedotin (EnaV), a novel anti-AXL human IgG1 and monomethyl auristatin E antibody–drug conjugate, demonstrated antitumor activity in preclinical models, including non–small cell lung cancer (NSCLC). This phase 1/2 study assessed the safety and preliminary efficacy of EnaV in solid tumors. Patients and Methods: This study comprised dose-escalation and dose-expansion phases; both phases investigated EnaV once every 3 weeks (Q3W) and EnaV on days 1, 8, and 15 of a 28-day cycle (3Q4W). Primary objectives determined the maximum tolerated dose (dose escalation) and safety (dose expansion). Pharmacokinetic profile, antitumor activity, and AXL expression were also assessed. Results: During dose escalation, 32 patients received EnaV Q3W; 15 received EnaV 3Q4W. The maximum tolerated dose and recommended phase 2 dose were 2.2 mg/kg in Q3W and 1.0 mg/kg in 3Q4W schedules. In dose expansion, 189 patients received EnaV Q3W; 70 received EnaV 3Q4W. Common adverse events in dose expansion included fatigue, constipation, nausea, decreased appetite, and diarrhea. Overall response rates ranged from 4.5% to 12.5% with Q3W dose schedule and from 9.1% to 11.5% with 3Q4W dose schedule. Disease control rates for NSCLC cohorts were 40.9% to 50.0%. NSCLC subset analysis demonstrated correlation between radiomics signature and disease control. The relationship between clinical activity and AXL expression was not apparent. Conclusions: EnaV had an acceptable safety profile; however, because the evaluation of antitumor activity did not show clinically meaningful responses, clinical development of EnaV was discontinued. Significance: EnaV, an anti-AXL human IgG1 and monomethyl auristatin E antibody–drug conjugate, showed single-agent antitumor activity in preclinical models. This phase 1/2 study of EnaV demonstrated a manageable safety profile and antitumor activity in selected tumor types. Further studies exploring alternative targeting modalities, patient selection, and/or combinations are needed.

Objective: To characterize pediatric patients experiencing unplanned intraoperative extubation (UIE) during cleft lip (CL) and cleft palate (CP) repair and assess postoperative outcomes. Design: Retrospective cohort study using the 2019–2023 National Surgical Quality Improvement Program–Pediatric database. Setting: Multicenter surgical registry of pediatric operations. Patients: Children undergoing CL repair (<1 year) or CP repair (<3 years). Interventions: Not applicable. Main Outcome Measure(s): Incidence of UIE, demographic and operative characteristics, and 30-day postoperative complications. Results: Among 17 047 cases, UIE occurred in 0.37% of CL repairs and 0.20% of CP repairs. Patients who experienced UIE had similar baseline characteristics to those without UIE but demonstrated significantly longer operative and anesthesia times for both procedures. Despite these intraoperative events, no cases of death, pneumonia, or unplanned reintubation occurred postoperatively, and overall 30-day complication rates remained low. Conclusions: UIE during CL and CP repair is rare and not associated with major postoperative complications.