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Background: Southeast Asian Americans (SEAAs) experience a disproportionately high burden of hepatocellular carcinoma (HCC), with incidence in several subgroups (i.e., Cambodian, Laotian, and Vietnamese individuals) reaching up to nine times that of non-Hispanic Whites. HCC in SEAAs is largely driven by chronic hepatitis B (HBV), hepatitis C (HCV), metabolic dysfunction–associated steatotic liver disease (MASLD), and alcohol-associated liver disease (ALD). Despite established screening guidelines, under-detection and delayed diagnosis remain common. Objective: To summarize epidemiologic patterns, risk factors, screening challenges, and potential interventions aimed at reducing HCC disparities among SEAAs. Design and Methods: This narrative review synthesized evidence from population based epidemiologic studies, community-based interventions, health services research, and policy analyses. Attention was given to studies reporting disaggregated SEAA subgroup data. Findings derived from SEAA specific studies were distinguished from evidence drawn from broader Asian American or general cirrhosis populations, with inferential steps explicitly noted where subgroup specific data were limited. Key Findings: HCC incidence varies widely across SEAA subgroups, with elevated HBV- and HCV-related HCC in Vietnamese, Cambodian, and Laotian communities, and increasing MASLD-related HCC including among lean individuals who fall outside many surveillance frameworks. Screening and surveillance remain suboptimal, with fewer than 30% of patients with cirrhosis receiving recommended semiannual HCC surveillance and even lower uptake among SEAAs. Barriers include low HBV/HCV screening rates, limited disease awareness, language barriers, underinsurance, provider knowledge gaps, and lack of automated EHR-based reminders. Structural challenges such as poverty, transportation barriers, and limited access to specialty care further delay diagnosis. Proposed Interventions: Culturally tailored outreach programs, bilingual navigators, and community-based screening initiatives have demonstrated improved HBV/HCV testing and linkage to care. AI-enabled EHR tools may enhance identification of high-risk patients, streamline follow-up, and increase surveillance adherence. Expanded use of non-invasive fibrosis assessment and recognition of MASLD-related risk in non-obese individuals may support earlier detection. Policy priorities include mandatory Asian subgroup data disaggregation, expanded insurance coverage, and strengthened community-level healthcare infrastructure. Conclusions: SEAAs face a substantial and preventable HCC burden. A coordinated approach combining culturally tailored community engagement, improved provider support systems, and policy reforms is essential to improving early detection and reducing HCC disparities in this diverse population.

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.

BACKGROUND: Hemorrhagic risk in dural arteriovenous fistulas (dAVFs) is largely determined by venous anatomy, but the contribution of systemic cardiovascular factors and their medical therapy remains poorly defined. This study examined associations between cardiovascular risk factors and antithrombotic use and hemorrhagic presentation, angiographic obliteration, and early functional outcomes after treatment. METHODS: We analyzed 1350 adults with intracranial dAVFs from the international Consortium for Dural Arteriovenous Fistula Outcomes Research registry, which retrospectively accrued cases across 14 centers in 4 countries between 1990 and 2017. Demographics, cardiovascular comorbidities, antithrombotic use, angioarchitectural features, treatment strategies, and follow-up outcomes were collected from prospectively maintained databases. Primary end points were hemorrhagic presentation, angiographic obliteration, and 90-day functional status after treatment. Univariable and multivariable logistic regressions were performed with model-specific adjustments. RESULTS: Hemorrhage occurred in 375 patients (27.8%) and was most strongly associated with high-grade dAVF classification and male sex; antithrombotic therapy was associated with lower odds of hemorrhagic presentation. Other cardiovascular risk factors showed no independent relationship with bleeding. Angiographic obliteration was achieved in 621 of 845 patients (73.5%). Hemorrhagic onset, high dAVF grade, and surgical treatment were independently associated with angiographic obliteration, whereas smoking and embolization demonstrated only nonsignificant trends after adjustment. At 90 days, 934 patients (88.9%) were functionally independent. Baseline modified Rankin Scale score was the strongest factor associated with 90-day functional outcome, while neither cardiovascular comorbidities nor treatment modality independently influenced functional status. CONCLUSIONS: In this large multicenter dAVF cohort, hemorrhagic presentation was most strongly associated with venous angioarchitecture. Male sex and antithrombotic therapy were also independently associated with hemorrhagic presentation. Angiographic obliteration was common, particularly among surgically treated lesions, and 90-day functional outcome was most strongly associated with baseline functional status.

Abstract Background and Aims Burnout affects millions of healthcare workers worldwide, from food service and nurses to physicians and leaders, impairing worklives and threatening health system stability. Methods An international collaborative, PREVAIL, was created to reduce burnout globally. Leaders from six continents shared structured insights into the local state of wellness and burnout contributors and mitigators, which were then subjected to a formal thematic (qualitative) analysis to identify common and region-specific themes. Results Across continents, findings showed the global state of well-being was in danger, though threats varied by region: long shifts in Africa, heavy workloads in Asia, austerity-prone environments in Europe and financially driven care in North America. Vulnerable worker groups included women, nurses, and primary care. Mitigators included workload and schedule adjustments (Africa), shift policies with fair pay (Asia), leader support and regular well-being assessments (Australia), improved psychosocial services (Europe), organizational wellness support and career development (North America), and trainee support (South America). Conclusions A proposed “common pathway” framework explains shared drivers of poor workforce well-being and provides actionable steps for promoting compassionate, supportive environments worldwide. Implications/Learning Points Adopting a coordinated international approach may prevent devastating workforce shortages over the comingdecades. Burnout assessment and reduction in the global workforce is a high priority.

Introduction: The objective of the study was to evaluate the prevalence of cardiovascular, renal, and hepatic biomarkers that fall outside guideline-based thresholds in adults with type 1 diabetes (T1D), and to identify demographic and clinical factors associated with these biomarkers. Methods: This observational study linked data on 2,923 adults with T1D from the T1D Exchange Registry and NorstellaLinQ’s laboratory data (2022–2023). Prevalence of biomarkers outside guideline-recommended thresholds was calculated. Generalized estimating equations (GEE) were used to model associations with age, sex, race/ethnicity, insurance, T1D duration, body mass index (BMI), and hemoglobin A1c (HbA1c), while accounting for within-subject correlation due to repeated measures. Results: Elevated low-density lipoprotein (LDL) cholesterol (≥70 mg/dL, above the recommended goal for individuals with diabetes at high risk for atherosclerotic cardiovascular disease) was common (80.2%), as were overweight (33.8%) and obesity (30.3%). Additional findings included high total cholesterol (≥200 mg/dL, 22.6%), low high-density lipoprotein (HDL) cholesterol (<40 mg/dL males, <50 mg/dL females, 13.4%), elevated urinary albumin-to-creatinine ratio (≥30 mg/g, 13.0%), reduced estimated glomerular filtration rate (<60 mL/min/1.73 m 2 , 6.2%), and elevated fibrosis-4 index (FIB-4) (≥1.3, 14.4%). In adjusted GEE models, higher HbA1c was significantly associated with increased odds of abnormal cardiovascular and renal biomarkers across most measures. Male sex and BMI were linked to lower HDL cholesterol, while older age was strongly associated with elevated FIB-4. Conclusion: Obesity and elevated LDL cholesterol are highly prevalent in adults with T1D, indicating substantial cardiometabolic risk. The lack of outcome trials in this population underscores the need for studies to evaluate strategies to improve weight and lipid management and thereby reduce cardiovascular and renal risk in adults with T1D.

Abstract INTRODUCTION Alzheimer's disease neuropathologic change (ADNC) classification identifies not/low and intermediate/high levels of neuropathology. Our goal was to assess how frequently a positive amyloid positron emission tomography (PET) scan indicates not/low ADNC and whether this autopsy finding can occur >10 years after a positive amyloid PET. METHODS Participants with positive amyloid PET scans were categorized by levels of ADNC at autopsy, grouped by time from initial positive amyloid PET to time of death (<5 years, 5 to <10 years, or 10+ years). RESULTS Among those with a positive amyloid PET scan, the majority had intermediate/high ADNC at autopsy (234/259, 90%). In the group with 10+ years between a positive amyloid PET and death ( n = 39) not/low ADNC occurred in 3/39 (8%). DISCUSSION Not/low ADNC is uncommon among those with positive amyloid PET scans. After 10+ years, it is possible but rare for a positive amyloid PET scan to represent an indolent state of neuropathology.

Summary Cancer genome sequencing is essential for understanding tumor evolution and advancing precision medicine. 1 However, reference gaps and germline variants obscure detection of small and large somatic variants and methylation in repetitive regions. 1–3 It is common for tumor cells to gain or lose chromosome arms due to somatic structural changes that occur inside highly repetitive satellite DNA sequences in the centromeres. 4 To identify the full spectrum of somatic variants, including complex rearrangements, we construct and curate near-complete, haplotype-resolved assemblies of the most recent common ancestor of an early-passage broadly-consented hypodiploid pancreatic cancer cell line and matched normal tissues. The tumor assembly completely recapitulates all 35 tumor chromosomes observed with karyotyping, with multiple translocation-induced hybrid chromosomes. The hybrid chromosomes contain putative functional dicentric and fused centromeres, nested foldback inversions causing 14 breakpoints with a haplotype switch in a single event, and centromeric satellite tandem duplications up to 136 kbp. Direct comparison of tumor and normal assembly haplotypes uncovers >7,000 variants altering >1 Mbp of sequence in repetitive regions that have been hidden by reference gaps and germline variants. 44 % of somatic small variants change representation because they alter germline variants on GRCh38, impacting mutational signatures and kataegis/omikli clusters. Most somatic LINE insertions originate from two hypomethylated non-reference germline LINE insertions, highlighting their impact on insertion mutation burden. These assemblies demonstrate that centromeric, acrocentric, and telomeric regions conventionally excluded from analysis harbor extensive somatic and epigenetic changes. Resolving complete tumor genomes enables a deeper understanding of cancer structural plasticity and the endpoints of breakage-fusion-bridge cycles. These assembled, curated paired normal-tumor benchmarks will serve as a critical foundation for developing future algorithms to characterize the most intractable regions of cancer genomes.

This multicenter, single-arm, phase 1/2 study evaluated the safety and efficacy of CD19-directed allogeneic chimeric-antigen-receptor (CAR) immunotherapy CTX110 in adult patients with relapsed/refractory (r/r) B-cell non-Hodgkin lymphoma (NHL). Patients received 1 or 2 treatment courses: standard lymphodepletion, followed by 1 CTX110 infusion at dose levels (DLs) 1-4 (3-60 × 107 CAR T-cells; dose escalation, N=32), or 2 infusions at DL4 on days 1 and 35 (cohort expansion, N=31). Primary endpoints in dose escalation and cohort expansion were incidence of dose-limiting toxicities and objective response rate, respectively. CTX110 was administered to 63 heavily pretreated patients: 59% primary refractory, 43% with ≥3 prior treatment lines. Among 57 patients whose first infusion was DL≥3, rates of objective and complete response (CR) were 65% and 39%, respectively. Among 22 patients achieving CR, 5 (23%) had ongoing CR at data cutoff, with 15-50 (median 34) months follow-up. The 2-infusion regimen appeared to prolong response duration compared to 1 infusion (hazard ratio 0.65). Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) were reported in 54% and 13% of treated patients, respectively, including 2 grade ≥3 cases each. The most common grade ≥3 adverse events were neutropenia (59%), and anemia and thrombocytopenia (35% each). Serious adverse events occurred in 32% of treated patients, including CRS (14%), ICANS (8%), and febrile neutropenia (6%). In this r/r NHL population, CTX110 was well-tolerated, resulting in clinically meaningful responses at DL≥3, with a second infusion demonstrating evidence of further clinical benefit. This trial (NCT04035434) was registered at www.clinicaltrials.gov.