Citations

Aims The use of jumbo femoral heads, defined as those with a diameter of ≥ 40 mm, in primary total hip arthroplasty (THA) has gained popularity, to mitigate dislocation. The aim of this study was to determine the risk of dislocation, implant survival, and clinical outcomes of a large cohort of primary THAs with jumbo femoral heads. Methods We conducted a retrospective analysis of 1,828 primary THAs with jumbo femoral heads, which were undertaken for osteoarthritis, in 1,578 patients between January 2000 and December 2022, at a single academic medical centre. The femoral head diameter was 40 mm in 1,584 THAs (87%) and 44 mm in 244 THAs (13%). The outer diameter of the acetabular component ranged from 52 mm to 72 mm in those with 40 mm heads, and from 54 mm to 78 mm in those with 44 mm heads. The types of bearing included ceramic-on-highly cross-linked polyethylene (1,229 THAs; 67%) and metal-on-polyethylene (599 THAs; 33%). Elevated liners were used in 472 THAs (26%) and 1,083 (59%) were lateralized. The most common operative approach was posterior (1,388 THAs; 76%). Outcomes of interest included the rate of dislocation, revision for dislocation, any revision, any reoperation, and the Harris Hip Score (HHS). The mean age of the patients at the time of THA was 64 years (8 to 94); 1,477 (81%) were male, and their mean BMI was 28 kg/m² (5 to 55). The mean follow-up was six years (2 to 14). Results The ten-year survival free of dislocation was 97% (95% CI 96 to 98; 97% for 40 mm heads (95% CI 95 to 98) and 99% for 44 mm heads (95% CI 97 to 100) (hazard ratio 3 (95% CI 1 to 14); p = 0.106)). The ten-year survival free of revision for dislocation was 99.6% (95% CI 99 to 100) (99.5% for 40 mm heads (95% CI 98 to 100) and 100% for 44 mm heads (p = 0.546)). The ten-year survival free of any revision and any reoperation was 95% (95% CI 94 to 97) and 93% (95% CI 91 to 95), respectively. There were no significant differences in survival free of any revision (p = 0.746) or any reoperation (p = 0.762) between the two groups. Conclusion In this large single-centre study of the use of jumbo femoral heads in primary THAs, the ten-year survival free of dislocation was 97%, with extremely few revisions for dislocation. These results highlight the potential for jumbo femoral heads to reduce the risk of dislocation and enhance implant longevity without compromising other clinical outcomes. Cite this article: Bone Joint J 2025;107-B(7):698–706.

Background: In the emergency setting, many diagnostic pathways incorporate change in high-sensitivity cardiac troponin (hs-cTn) concentrations (i.e., the delta) to classify patients as low-risk (rule-out) or high-risk (rule-in) for possible myocardial infarction (MI). However, the impact of analytical variation on the delta for correct classification is unknown, especially at concentrations below and around the 99th percentile. Our objective was to assess the impact of delta variation for correct risk classification across the European Society of Cardiology (ESC 0/1 h and 0/2 h), the High-STEACS, and the common change criteria (3C) pathways. Methods: A yearlong accuracy study for hs-cTnT was performed where laboratories across Canada tested three patient-based samples (level 1 target value = 6 ng/L, level 2 target value = 9 ng/L, level 3 target value = 12 ng/L) monthly across 41 different analyzers. The assigned low-delta between levels 1 and 2 was 3 ng/L (i.e., 9 − 6 = 3 ng/L) and the assigned high-delta between levels 1 and 3 was 6 ng/L (i.e., 12 − 6 = 6 ng/L). The low- and high-deltas for each analyzer were determined monthly from the measured values, with the difference calculated from the assigned deltas. The obtained deltas were then assessed via the different pathways on correct classification (i.e., percent correct with 95% confidence intervals, CI) and using non-parametric analyses. Results: The median (interquartile range) difference between the measured versus assigned low-delta (n = 436) and high-delta (n = 439) was −1 ng/L (−1 to 0). The correct classification differed among the pathways. The ESC 0/1 h pathway yielded the lowest percentage of correct classification at 35.3% (95% CI: 30.8 to 40.0) for the low-delta and 90.0% (95% CI: 86.8 to 92.6) for the high-delta. The 3C and ESC 0/2 h pathways yielded higher and equivalent estimates on correct classification: 95.2% (95% CI: 92.7 to 97.0) for the low-delta and 98.2% (95% CI: 96.4 to 99.2) for the high-delta. The High-STEACS pathway yielded 99.5% (95% CI: 98.4 to 99.9) of correct classifications for the high-delta but only 36.2% (95% CI: 31.7 to 40.9) for the low-delta. Conclusions: Analytical variation will impact risk classification for MI when using hs-cTn deltas alone per the pathways. The 3C and ESC 0/2 h pathways have <5% misclassification when using deltas for hs-cTnT in this dataset. Additional studies with different hs-cTnI assays at concentrations below and near the 99th percentile are warranted to confirm these findings.

PURPOSE Automated curation of breast cancer treatment data with minimal human involvement could accelerate the collection of statewide and nationwide evidence for patient management and assessing the effectiveness of treatment pathways. The primary challenges are the complexity and inconsistency of structured clinical data streams and accurate extraction of this information from free-text clinical narratives. MATERIALS AND METHODS We proposed a hybrid two-phase information extraction framework that combined a Unified Medical Language System parser (phase-1) with a fine-tuned large language model (LLM; phase-2) to extract longitudinal treatment timelines from time-stamped clinical notes. Our framework was developed through end-to-end joint learning as a question-answering model, where the model was trained to simultaneously answer five questions, each corresponding to a specific treatment. RESULTS We fine-tuned and internally validated the model on 26,692 patients with breast cancer (diagnosed between 2013 and 2020) receiving treatment at Mayo Clinic and externally validated the model on 162 randomly selected patients from Stanford Healthcare. Zero-shot LLM (out-of-the-box) had high specificity but low sensitivity, indicating that although these frameworks are useful for generic language understanding, they are lacking in terms of targeted clinical tasks. The proposed model achieved 0.942 average AUROC on the internal and 0.924 on the external data, demonstrating only marginal drop in performance when evaluated on external. The proposed model also achieved better trade-off between sensitivity (average: 79.2%) and specificity (average: 76.2%) compared with rule-based (average sensitivity: 70.5%, average specificity: 68.1%) and structured codes (average sensitivity: 64.1%, average specificity: 83.5%). CONCLUSION The proposed framework can extract temporal information about cancer treatments from various time-stamped clinic notes, regardless of the setting of treatment administration (inpatient or outpatient) or time frame. To support the cancer research community for such data curation and longitudinal analysis, we have packaged the code as a docker image, which needs minimal system reconfiguration and shared with an open-source academic license.

Abstract Background Dasatinib is an oral inhibitor of the Src kinase family, with preclinical data indicating impact on gliomagenesis, tumor invasion, and radiosensitivity. Methods North Central Cancer Treatment Group N0877 is a phase 1 dose escalation and phase II randomized study evaluating the maximum tolerated dose (MTD), safety, and efficacy of dasatinib with radiation and temozolomide (TMZ) for glioblastoma. Following identification of the MTD, adult patients with a histologic diagnosis of glioblastoma were randomized 2:1 between dasatinib given with standard concurrent and adjuvant TMZ, versus placebo with standard concurrent and adjuvant TMZ. Radiation dose was 60 Gy in 30 fractions. The primary endpoint was overall survival (OS). Secondary endpoints included progression-free survival (PFS), toxicity, and quality of life. Results Thirteen patients were enrolled in the phase I component and established the MTD and phase II dose of 150 mg given daily. A total of 204 patients were enrolled in the phase II component. OS was not different between arms (median OS 15.6 months for dasatinib compared to 19.3 months for placebo, hazard ratio:1.21 favoring placebo, 95% CI: 0.88–1.65, log-rank P-value: .238). Similarly, PFS was not significantly different between the dasatinib and placebo arms. There was a significant increase in anemia, nausea, and creatinine elevation with dasatinib, but significantly more grade 3 lymphopenia with placebo. Conclusions The addition of dasatinib to standard chemoradiation did not improve outcomes for patients with glioblastoma. Clinical Trial Identifier NCT00869401.

AbstractDespite advances in acute myeloid leukemia (AML) treatment, significant unmet medical needs remain. Surrogate end points for overall survival can accelerate the approval of novel therapies. Measurable residual disease (MRD) is a promising surrogate end point candidate, providing a sensitive and quantitative assessment of disease burden. Numerous studies have demonstrated that negative MRD status—across diverse methodologies, assessment timepoints and thresholds, patient subgroups, and clinical settings—independently predicts improved survival. Although MRD can inform therapeutic decisions at the patient level, its formal integration as a primary surrogate end point in regulatory frameworks for clinical trials requires rigorous validation. MRD Partnership and Alliance in AML Clinical Treatment (MPAACT) is a research consortium among industry and academic leaders. MPAACT actively engages with regulatory agencies, health technology assessment bodies, technology vendors, and patient groups to establish a pathway for validating MRD as a surrogate end point in AML clinical trials. For the current article, the authors reviewed the status of MRD assessment, its use in recent clinical trials, current MRD assessment methodologies, standardization, regulatory guidance, statistical approaches, and patient access considerations necessary for MRD to become a surrogate clinical trial end point. The extensive collaboration between MPAACT, global industry, and academic partners—including data sharing and resource integration—underscores the collective commitment to advancing AML therapies. Establishing MRD as a surrogate end point could accelerate the development and approval of innovative treatments, ultimately improving patient outcomes.

Background Prompt diagnosis of acute central retinal artery occlusion (CRAO) is crucial for therapeutic management and stroke prevention. However, most stroke centers lack onsite ophthalmic expertise before considering fibrinolytic treatment. This study aimed to develop, train, and test a deep learning system to detect hyperacute CRAO on retinal fundus photographs within the critical 4.5‐hour treatment window and up to 24 hours after visual loss to aid in secondary stroke prevention. Methods Our retrospective, cross‐sectional study included 1322 color fundus photographs from 771 patients with acute visual loss due to CRAO, central retinal vein occlusion, nonarteritic anterior ischemic optic neuropathy, and healthy controls. Photographs were collected from 9 expert neuro‐ophthalmology centers in 6 countries, including 3 randomized clinical trials. Training included 1039 photographs (517 patients), followed by testing on 2 data sets: (1) hyperacute CRAO (54 photographs, 54 patients) and (2) CRAO within 24 hours after visual loss (110 photographs, 109 patients). Results The deep learning system achieved an area under the receiver operating characteristic curve of 0.96 (95% confidence interval (CI), 0.95–0.98), a sensitivity of 92.6% (95% CI, 87.0–98.0), and a specificity of 85.0% (95% CI, 81.8–92.8) for detecting CRAO at hyperacute stage, with similar results within 24 hours. The deep learning system outperformed stroke neurologists on a subset of hyperacute testing data set (120 photographs, 120 patients). Conclusions A deep learning system can accurately detect hyperacute CRAO on retinal photographs within a time window compatible with urgent fibrinolysis. If further validated, such systems could improve patient selection for fibrinolytic trials and optimize secondary stroke prevention. Registration URL: https://www.clinicaltrials.gov ; Unique identifier: NCT06390579.

We investigated the prognostic impact of blast counts, TP53 allelic state determinants (number of hits, del(17p), variant allele frequency, complex karyotype),and a novel karyotypic clonal cell fraction (≤50% clonal cells vs >50% clonal cells (termed ‘CK50’)) in 495 individuals with TP53- mutated ( TP53 MUT ) myeloid neoplasms. Outcome examined was 24-month survival (OS24). The cohort (median age 71) included 29% (144/495) myelodysplastic syndromes (MDS)/MDS-acute myeloid leukaemia (AML) (1%–19% blasts) and 71% (351/495) AML (≥20% blasts), with 18% (81/460) having low CK50. Overall, 83% received front-line hypomethylating agents. Higher blast counts (<20% vs ≥20%) were marginally associated with CK50 (p=0.08). In the OS24 analysis, blast count showed a marginal association with OS24 (HR 1.3 (95% CI 1.0 to 1.6); p=0.07), while CK50 predicted significantly inferior outcomes (HR=1.7 (95% CI 1.2 to 2.3); p=0.002). In a multivariable model including all TP53 allelic state determinants, only CK50 and complex karyotype remained relevant for predicting adverse outcomes.

Objective: This study evaluated the surgical and long-term patient-reported quality of life outcomes of patients undergoing esophagectomy with gastric advancement. Methods: A retrospective review was performed of all patients undergoing esophagectomy with gastric advancement from 2005 to 2016. Quality of life outcomes were evaluated using the European Organization for research and treatment of cancer quality of life questionnaire - esophageal cancer module (QLQ-OES18), which covered 10 symptom scales: dysphagia, trouble swallowing saliva, choking when swallowing, eating, dry mouth, trouble with taste, trouble with coughing, trouble speaking, reflux, and pain. Results: A total of 129 patients were followed up to 16 years (791.3 patient-years). The median age was 63.5 (IQR 55.9-69.3) years, and 79.9% were male. Eighty-six percentage (111/129) of patients had esophageal malignancy as their operative indication. Median survival was 7.1 years, with patients with benign disease experiencing longer postoperative survival ( P = .006). The response rate to QLQ-OES18 surveys was 53.7% (22/41; median follow-up: 10.4 years). Patients who experienced early postoperative complications were more likely to report trouble with coughing ( P = .032) than those who did not experience early complications. However, postoperative leaks were not associated with worsened QOL. Of note, age ≥ 65 years, obesity status, surgical indication, location of the primary esophageal lesion, tumor stage, and the occurrence of delayed postoperative complications were not associated with long-term QOL (all P > .05). Conclusion: Patients undergoing esophagectomy with gastric advancement generally had good quality of life 10 years postoperatively, though early postoperative complications and gender appeared to influence symptom burden. These findings may improve pre and postoperative patient counseling.