Citations

By 2045, more than three quarters of global cancer deaths are projected to occur in low- and middle-income countries (LMICs); however, the global availability of cancer care remains constrained by high costs and inequitable access. Value-based frameworks that integrate clinical benefit with affordability, feasibility, and equity are essential to better guide research prioritization, resource allocation, and regulatory policies in LMICs. A key component of a value-based approach is the generation of high-quality, locally relevant data to support evidence-based implementation of cancer prevention and control strategies. Herein, we provide three contemporary examples from JCO Global Oncology which demonstrate how economic evaluation in cancer research can address locally relevant, health system–specific questions.

Background: Prosthetic joint infections (PJIs) pose a significant treatment challenge due to biofilm-associated resistance, which limits antibiotic effectiveness. Bacteriophages, naturally occurring viruses that selectively infect and lyse bacteria, can disrupt biofilms, potentially enhancing antibiotic activity. We present the case of a male in his 70s with a history of total hip arthroplasty in 1973 who developed a chronic methicillin-susceptible Staphylococcus aureus (MSSA) PJI. Despite eight surgical interventions and multiple courses of suppressive antibiotics, the infection persisted, necessitating the use of bacteriophage therapy. Methods: The patient's MSSA isolate was sent to a bacteriophage laboratory in Quebec, which identified effective bacteriophages, and a two-bacteriophage cocktail was selected. Following approval by Health Canada and the University of Calgary (REB23-1733), bacteriophages were administered during a planned incision and drainage (I&D). Locally, bacteriophage was applied topically into the hip, followed by 2 weeks of twice-daily intravenous bacteriophage therapy with standard-of-care intravenous antibiotics. Results: Therapy was well tolerated except for initial mild rigors. Now, 24 weeks after bacteriophage administration, there is cessation of pain, normalization of inflammatory markers, and significant improvement in quality of life while continuing on suppressive antibiotics. Conclusions: Bacteriophage therapy was safe in our case, and emerging evidence is promising for its use in PJIs. However, regulatory hurdles, cost, and lack of standardized protocols currently limit its use. Classified as experimental therapy in Canada, bacteriophage use is restricted to clinical trials. This case underscores the potential for broader adoption of bacteriophage therapy in managing PJIs across Canada.

Autoimmune diseases arise when B and T lymphocytes lose tolerance to self. Yet in most disorders, the underlying molecular determinants, including autoantibodies, epitopes and lymphocyte clones that drive tissue injury remain undefined. Rapid-onset obesity with hypothalamic dysfunction, hypoventilation and autonomic dysregulation (ROHHAD) is a rare and often fatal pediatric neuroendocrine syndrome with strong evidence of antigen-driven paraneoplastic autoimmunity, including association with the intracellular autoantigen ZSCAN1. However, the effector immune circuit and the epitope-level determinants operating within the hypothalamus and brainstem have remained unknown. To address this challenge in ROHHAD and more broadly in autoimmune disease, we developed the Autoimmune Epitope and immunoGlobulin/Immune-receptor identification System (AEGIS), an integrated framework that links immune repertoires to their cognate self-epitopes. AEGIS combines B cell and T cell receptor profiling from sites of tissue injury with high-resolution epitope mapping, direct sequencing of antigen-specific autoantibodies, in silico antibody-antigen folding, selection, and T cell antigen discovery. Applied to a deeply phenotyped child with ROHHAD, AEGIS revealed a compartmentalized, clonally restricted immune response in which brain-deposited IgG and expanded cerebrospinal fluid B cell and CD4 T cell clonotypes converged on shared ZSCAN1 epitopes, resolved to minimal determinants and peptide-MHC ligands. These findings provide a clone- and epitope-linked mechanistic map of ROHHAD autoimmunity and establish a generalizable framework for identifying candidate pathogenic clones and antigens across diverse autoimmune diseases.

Background/Objectives: To identify predictors of successful fusion and adjacent segment disease (ASD) following ALIF. Methods: Records of patients undergoing one- or two-level ALIF were queried for baseline and postoperative radiographic data, demographics, operative notes, and implant characteristics. All had ≥1 year of follow-up with CT, and multivariable Cox regression was used to identify predictors of radiographic fusion through the interbody, ASD, and ASD requiring reoperation. Results: In total, 177 patients (median 59 yr; 52.5% male) were treated at 245 unique levels, of which 193 fused (81.3% with posterior fixation and 59.6% with standalone), 43 had ASD (17.6%), and 14 had ASD requiring reoperation (5.7%). Fusion was predicted by anterior cage placement (HR 0.94/mm; 95% CI [0.90, 0.98]; p = 0.003) and BMP use (HR 1.92; [1.15, 3.18]; p = 0.012). Radiographic ASD was predicted by older age (HR 1.08 per year; [1.03, 1.14]; p < 0.001), undergoing a revision [vs. index] fusion operation (HR 3.51; [1.44; 8.59]; p = 0.006), lower preoperative disc height (HR 0.83/mm; [0.74, 0.94]; p = 0.003), and preoperative facet vacuum phenomenon (HR 2.46; [1.18, 5.15]; p = 0.017). None of the extracted variables predicted reoperation for ASD. Conclusions: BMP use along with anterior cage placement and posterior fixation may improve the odds of fusion through the interbody following one- or two-level ALIF. Adjacent segment pathology is more common in patients with greater preoperative degenerative pathology (vacuum sign; more collapsed disc) and advanced age. Pelvic fixation did not improve fusion odds, but the data highlight the benefits of supplementary posterior fixation vs. standalone ALIF.

Purpose: To determine the clinical utility of the assessment of preoperative orbital compliance in predicting the amount of postoperative proptosis reduction in patients with stable-phase thyroid eye disease who undergo orbital fat decompression surgery. Methods: A retrospective chart review was conducted of stable-phase thyroid eye disease patients who underwent orbital fat decompression by a single surgeon. Orbital compliance was measured preoperatively as axial globe displacement (in millimeters) using a Hertel exophthalmometer. Displacement ≥2.5 mm was classified as high compliance and <2.5 mm as low compliance. Radiographic thyroid eye disease type, preoperative proptosis, and intraoperative fat volume removed were recorded. Linear regression analysis determined whether orbital compliance independently predicted postoperative proptosis reduction. Levene’s test assessed variability between groups. Results: Forty-six orbits from 24 patients were included, 15 orbits with low compliance and 31 with high orbital compliance. Patients with high orbital compliance had a mean postoperative proptosis reduction of 3.19 mm (range 0.5–6.0 mm) while patients with low orbital compliance had a mean proptosis reduction of 2.67 mm (range 2.0–3.5 mm). On average, higher preoperative orbital compliance led to 0.959 mm greater proptosis reduction compared with low orbital compliance, when accounting for radiographic thyroid eye disease type and volume of fat removed intraoperatively ( p = 0.048). Variability in proptosis reduction was higher among the high orbital compliance group ( p = 0.00085). Conclusions: Higher preoperative orbital compliance results in greater proptosis reduction. However, patients with high orbital compliance have greater variability in proptosis reduction, suggesting that surgical outcomes are less predictable among these patients.

BACKGROUND Differential awakening is a well-known, yet poorly understood phenomenon seen in patients with intracranial pathologies. Because acute postoperative neurological decline has many potentially reversible causes, distinguishing differential awakening from other etiologies is critical. To the authors’ knowledge, differential awakening has not been reported following peripheral nerve procedures. OBSERVATIONS A 40-year-old man presented with a 1.5-year history of painful bilateral cervical and right lumbosacral radiculoplexus neuropathy recently associated with bilateral facial and vestibulocochlear neuropathy. He had not responded to treatment trials. A sciatic nerve lesion in the sciatic notch was identified on imaging and an open biopsy of the posterior femoral cutaneous nerve was pursued. Immediately after emergence from anesthesia, he demonstrated a complete inability to dorsiflex or plantar flex the right foot, despite minimal intraoperative manipulation of the sciatic nerve. Over the ensuing hour, motor function progressively returned to baseline. The transient postoperative motor deficit was attributed to differential awakening of the sciatic nerve. Pathological analysis confirmed high-grade B-cell lymphoma. LESSONS Differential awakening may be an underrecognized cause of transient neurological worsening during emergence from anesthesia following peripheral nerve surgery. Further investigation is needed to clarify the underlying mechanisms and define its incidence and risk factors. https://thejns.org/doi/10.3171/CASE251028

Importance Current risk prediction guidelines for hypertrophic cardiomyopathy predict only sudden cardiac death and are imperfect, leading to avoidable deaths and unnecessary implantable cardioverter defibrillators. Objective To combine prospectively collected clinical history, imaging, genetic, and biomarker data to improve risk prediction of adverse events in hypertrophic cardiomyopathy. Design, Setting, and Participants A total of 2750 patients with hypertrophic cardiomyopathy were prospectively enrolled in the registry-based study from 44 sites in North America and Europe with expertise in hypertrophic cardiomyopathy and cardiac magnetic resonance (CMR) imaging. Participants were enrolled from April 1, 2014, to April 7, 2017. Exposures Patients underwent a health history questionnaire, blood sampling for biomarkers and genotyping, and contrast-enhanced CMR. Patients were followed up yearly by telephone and through records review regarding event documentation. Main Outcomes and Measures The predefined composite adjudicated primary end point was time to first event for hypertrophic cardiomyopathy–related deaths; nonfatal sustained ventricular arrhythmias (VAs) requiring cardioversion or defibrillation; and left ventricular (LV) assist device implant or heart transplant. A secondary end point was a composite of sudden cardiac death and nonfatal VA events. The elastic-net method identified the most important predictors. Cox proportional hazards regression assessed associations with time to the first end point. Results Of the 2750 prospectively enrolled patients, 2698 (98%) had analyzable data after 9 were excluded because they had hypertrophic cardiomyopathy phenocopies and 43 withdrew. Of these remaining patients, 1919 (71%) were male, mean age was 50 years (SD, 11 years), and 423 (16%) were from underrepresented racial and minority groups. The mean follow-up was 6.9 years (SD, 2.1 years). The primary event model in 104 patients included LV scar as a percentage of LV mass by late gadolinium enhancement (LGE%; hazard ratio [HR], 1.86; 95% CI, 1.58-2.20; P &amp;lt; .001), LV mass index (HR, 1.09; 95% CI, 1.01-1.17; P = .03), LV end-systolic volume index (HR, 1.28; 95% CI, 1.12-1.46; P &amp;lt; .001 ), all per 10-unit increase, history of heart failure at study entry (HR, 2.89; 95% CI, 1.75-4.77; P &amp;lt; .001), and log N-terminal pro–B-type natriuretic peptide (NT-proBNP; HR, 1.41; 95% CI, 1.17-1.70; P &amp;lt; .001) level per log unit, (C index for all, 0.77). An LGE percentage of the LV mass of 9% or higher substantially increased the primary composite event rate ( P = .001). The secondary sudden cardiac death and VA risk factor model (in 69 patients) included LGE%, LV mass index, LV ejection fraction, and log(NT-proBNP) (C index, 0.76). Conclusions and Relevance These results provide prospective evidence for incorporating cardiac magnetic resonance and NT-proBNP in the evaluation of patients with hypertrophic cardiomyopathy. Trial Registration ClinicalTrials.gov Identifier: NCT01915615

This secondary analysis of a nonrandomized clinical trial identifies which participant characteristics were associated with selection of centralized or remote trial engagement.

Background/Objectives: Primary spinal sarcomas, encompassing both bone and soft tissue histotypes, demand individualized reconstruction due to heterogeneous tumor biology, anatomic complexity, and host environments compromised by radiation, systemic therapy, or prior surgery. This narrative review reframes post-resection spinal reconstruction through a precision-medicine lens. Methods: A structured literature review was performed using PubMed and Scopus, targeting articles published between 2000 and 2026. Searches encompassed spinal sarcoma reconstruction, radiation and fusion, biologic reconstruction, and emerging technologies. Results: Tumor grade, radiation exposure, and systemic therapy timing emerge as multiplicative determinants of reconstructive environment quality, with drug-class-specific perioperative effects warranting stratified management. Vascularized bone grafts achieve reliable fusion in compromised hosts where avascular constructs fail. A precision-oriented reconstructive ladder is proposed as a conceptual, hypothesis-generating framework to guide strategy selection. Hybrid PSI-VBG constructs may further expand reconstructive possibilities. The evidence base remains largely composed of small, retrospective series. Conclusions: Individualized strategies anchored in tumor biology and host environment are the cornerstone of durable spinal sarcoma reconstructions. The proposed framework requires prospective, multi-institutional validation. Standardized outcome definitions, prospective registries, and histotype-stratified analyses are needed to advance the field.