Citations

Background. Liver transplantation (LT) remains the most effective treatment for patients with hepatocellular carcinoma (HCC), offering 5-y recurrence rates as low as 15%. Recent advances in organ preservation, particularly hypothermic oxygenated machine perfusion (HOPE), have demonstrated the ability to attenuate ischemia–reperfusion injury (IRI). However, whether HOPE can reduce HCC recurrence rates by mitigating IRI remains an open question. In this study, we aimed to compare oncological outcomes after LT for HCC with and without the use of HOPE. Methods. We conducted a retrospective cohort study including 137 patients who underwent LT for HCC with grafts from donation after brain death. Risk factors for HCC recurrence were analyzed using Cox regression. To assess the impact of HOPE on oncological outcomes, propensity score matching was used to adjust for baseline differences. Results. Cox regression identified Milan Criteria status as a significant predictor of HCC recurrence. Among the 32 patients in the HOPE group, no HCC recurrence was observed over a median follow-up of 2.11 y. In contrast, within the control group of 105 patients, 8 (7.6%) experienced recurrence within 2 y posttransplantation. Although this translated into a significant difference in time-to-recurrence after propensity score matching, recurrence-free survival and overall survival did not differ significantly. Conclusions. Our findings suggest that HOPE treatment of donation after brain death liver grafts may reduce early HCC recurrence after LT. Although only nonsignificant trends were observed in recurrence-free survival and overall survival within the first 2 y posttransplant, these results underscore the potential of HOPE to influence oncological outcomes. Long-term follow-up, prospective randomized controlled trials, and basic research are warranted to further elucidate the role of HOPE and IRI.

Abstract Detection of germline pathogenic Variants (PVs) in BRCA1, BRCA2, and other genes that significantly elevate lifetime breast cancer (BC) risk are indications for early initiation of intensive screening. BRCA1/2 PVs guidelines recommend that magnetic resonance imaging (MRI) screening begin at age 25 and mammography screening at age 30. However, pregnancy, breastfeeding, and the postpartum period may complicate adherence due to patient concerns about MRI contrast, radiation exposure, logistical barriers, and limited guidance on timing. The incidence of BC peaks approximately 5 years postpartum, especially among women with a positive family history, and early-onset cancers are frequently aggressive, exacerbating the effects of delayed detection. We assessed screening and counseling practices during reproductive periods among women with or at risk for PVs to identify knowledge gaps and opportunities to improve surveillance. We conducted an anonymous survey from March 2023 through January 2025 distributed by Facing Our Risk of Cancer Empowered (FORCE) and social media platforms. Data were collected through a secure REDCap instrument and summarized with descriptive statistics and logistic regression. The Mayo Clinic Institutional Review Board deemed the study exempt. Among the 537 respondents (median age 43 years; 88.5% U.S. residents; 87.5% White), 66.2% were parous and 61.8% knew their family history of BC during pregnancy. Most women reported receiving counseling on screening breast examination, mammography, and MRI; however, 74-77% received no specific guidance about screening before, during, or after pregnancy and weaning. At the time of the survey, 89.9% had undergone BC screening, including 66.2% with annual mammography and 53.1% with annual MRI. Yet during pregnancy and breastfeeding, 69% reported not being screened. Parous women were more likely than nulliparous women to report screening (96.9% vs 85.6%,p<0.0001) and regular mammography (76.4% vs 57.2%,p<0.0001). Screening during pregnancy and breastfeeding was more common among the BRCA1/2 carriers than among carriers of other PVs. Breastfeeding affected screening behavior in 32% of the BRCA1/2 carriers versus 10.9% of other PV carriers, yet only 5.1% of PV carriers stopped breastfeeding to undergo imaging. After their last birth, many women postponed screenings for more than 3 years and only 20.5% received a mammogram within a year of their delivery. Overall, 28.8% of participants reported a history of cancer, of which 66.2% was BC. Approximately 20% of breast cancers reported were diagnosed within 3 years postpartum, with 8.6% occurring during lactation. Despite high rates of BC screening, most high-risk women received little counseling about imaging during pregnancy and breastfeeding, potentially contributing to delayed surveillance at a time of heightened BC risk. These findings highlight the need for targeted counseling, scheduling strategies to support MRI or other imaging during and after pregnancy, and development of novel early-detection tools such as blood or breastmilk biomarkers. Citation Format: Laura M. Pacheco-Spann, Sue Friedman, Diane Rose, William D. Foulkes, Zhihui Fang, Lauren E. Haydu, Mark E. Sherman. Breast Cancer Screening During Reproductive Years in Women with Germline Pathogenic Variants: Gaps in Counseling and Practice [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: The Rise in Early-Onset Cancers—Knowledge Gaps and Research Opportunities; 2025 Dec 10-13; Montreal, QC, Canada. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(23_Suppl):Abstract nr A029.

Abstract Background: The incidence of cancers diagnosed before age 50 has risen steadily over the past several decades. Survivorship research has not advanced at the same pace as these trends. Existing models of care were developed primarily for older adults and emphasize medical surveillance and risk reduction. Psychosocial dimensions, including anxiety, fear of recurrence, uncertainty about long-term health, and difficulty returning to social or professional roles, remain less consistently addressed. These needs are increasingly relevant as more individuals face the long-term impact of early-onset cancers. Methods: We are developing a digital survivorship model designed to extend support beyond the clinic and focus on psychosocial recovery in the early post-treatment period. The intervention integrates evidence-based behavioral strategies with participatory input from survivors, providers, and community partners. Features under development include educational modules, guided reflection, and interactive prompts to strengthen coping, resilience, and self-management. Evaluation will examine feasibility, acceptability, and early signals of impact using surveys, usage metrics, and qualitative interviews. Preliminary Results: Stakeholder engagement to date has demonstrated strong demand for resources that are both accessible and relevant to the life stage of early-onset survivors. Survivors report that many existing programs feel generic or better suited to older adults. Key priorities identified include managing fear of recurrence, navigating uncertainty about long-term effects, and balancing recovery with the responsibilities of family, career, and caregiving. These themes are informing design decisions and shaping evaluation measures. Conclusion: The rise in early-onset cancers creates an opportunity to expand the scope of cancer control to include survivorship as a central focus. Addressing psychosocial outcomes such as coping, resilience, and quality of life is essential for long-term health. Digital health strategies provide a scalable way to meet these needs by delivering tailored support that complements advances in prevention, detection, and treatment. Integrating survivorship into the broader response to early-onset cancers ensures progress is measured not only by survival but also by the ability of survivors to live well after treatment. Citation Format: Manisha Salinas. Psychosocial Survivorship Gaps in Early-Onset Cancers: Opportunities for Digital Health Research [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: The Rise in Early-Onset Cancers—Knowledge Gaps and Research Opportunities; 2025 Dec 10-13; Montreal, QC, Canada. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(23_Suppl):Abstract nr A008.

PURPOSE The HER2CLIMB-05 study (ClinicalTrials.gov identifier: NCT05132582 ) is investigating the efficacy and safety of adding tucatinib to trastuzumab and pertuzumab as first-line (1L) maintenance therapy in patients with human epidermal growth factor receptor 2–positive (HER2+) metastatic breast cancer (MBC). METHODS Patients with centrally confirmed HER2+ MBC without evidence of progression post induction therapy and no or asymptomatic brain metastases (BM) were enrolled. Patients were randomly assigned 1:1 to tucatinib (300 mg) or placebo twice a day combined with trastuzumab/pertuzumab. The primary end point is investigator-assessed progression-free survival (PFS); secondary end points include overall survival (OS), PFS per blinded independent central review, CNS-PFS, and safety. RESULTS Between March 2022 and July 2024, 654 patients were randomly assigned to tucatinib (n = 326) and placebo (n = 328) arms. All patients were female (median age, 54 years), 69.3% had de novo MBC, 52.6% were hormone receptor–positive, and 12.4% had presence/history of baseline BM. In this primary analysis, PFS was statistically significantly improved with addition of tucatinib versus placebo (hazard ratio, 0.641 [95% CI, 0.514 to 0.799]; P < .0001; median PFS: 24.9 v 16.3 months); a PFS benefit was seen regardless of the presence/absence of BM or hormone receptor status. OS data remain immature. The most common treatment-emergent adverse events (TEAEs) in the tucatinib arm were diarrhea (72.7%), nausea (33.1%), and elevated liver enzymes (ALT: 28.2%; AST: 25.8%), of which 6.1%, 0.9%, 13.5%, and 7.1%, respectively, were grade ≥3. In the tucatinib arm, 13.5% discontinued tucatinib because of TEAEs. CONCLUSION Tucatinib addition to trastuzumab and pertuzumab demonstrated improvement in PFS with no new safety signals identified and may be an option for 1L maintenance therapy in patients with HER2+ MBC.

Abstract Jagim, AR, Dobbs, WC, Horswill, CA, Twohey, E, Fields, JB, and Jones, MT. Prevalence and magnitude weight loss among collegiate wrestlers. J Strength Cond Res 40(1): 90–97, 2026—The purpose of this study was to examine the percentage of wrestlers who compete in their minimal weight class (MWC), and the magnitude of weight loss. Data from the 2023–2024 collegiate season were retrospectively analyzed resulting in a sample of 9,638 collegiate male wrestlers from the National Association of Intercollegiate Athletics ( n = 1,904) and all 3 divisions of the National Collegiate Athletics Association ( n = 7,734). All wrestlers completed skinfold assessments for weight certification at the start of the competition season. The lowest recorded weight class (LRW) achieved by each wrestler during the season was also recorded and used to determine magnitude of weight loss. Out of the 4,605 (53.2%) of wrestlers who competed in their MWC, their average amount of weight loss was significantly higher than those who did not compete in their MWC (3.9 ± 2.5 vs. 3.2 ± 2.9 kg.; p < 0.001), yet they had an initial lower body fat percentage (12.7 ± 2.9 vs. 17.5 ± 4.8%; p < 0.001). At the time of weight certification, wrestlers weighed 8.1 ± 4.5 (95% confidence interval (CI): 8.0–8.2; effect size (ES) = 1.8) kg more than their minimal wrestling weight. The LRW was 3.6 ± 2.9 (95% CI: 3.6–3.7; ES = 1.2) kg lower than their weight at the time of weight certification. Given that slightly more than half of the male wrestlers competed in their MWC, coaches and sports practitioners should recognize that not all athletes follow the traditional assumption of cutting to the lowest possible weight class. Importantly, those who did achieve their MWC had lower initial body fat percentages, limiting the amount of weight they could safely lose. This underscores the need for individualized weight management strategies that consider body composition and health implications.

Abstract This study delineates a novel multisystem caliber-persistent arteriopathy syndrome, fundamentally redefining the classical Dieulafoy's lesion from a localized gastrointestinal anomaly to a systemic congenital vasculopathy. Through integrated histopathological and genomic analysis of a forensic autopsy case, we identified pervasive arterial remodeling across seven organ systems— characterized by absent physiological tapering— indicating developmental angiogenic dysregulation. Whole-genome sequencing uncovered pathogenic variants in PDE8B , LRCH1 , and ADA genes, with functional enrichment analyses implicating dysregulated purine–cAMP signaling and cytoskeletal organization as core pathogenic mechanisms. These findings establish a genetic basis for the observed pan-vascular phenotype and highlight the necessity of systematic vascular screening in cases of unexplained multiorgan hemorrhage. This work provides a foundational framework for diagnosing and investigating congenital vascular malformations with hemorrhagic risk, urging a paradigm shift in clinical evaluation and etiological assessment.

Traditional solvents face limitations in environmental friendliness, biocompatibility, and functional tunability, which restrict their use in pharmaceuticals, biocatalysis, and biosensing.

ABSTRACT Stroke remains one of the most devastating complications following transcatheter aortic valve implantation (TAVI). Although cerebral embolic protection devices (CEPDs) have emerged to mitigate patients' risks, their impact on stroke risk, as well as other clinical and neurocognitive outcomes after TAVI, remains uncertain. We aimed to assess whether CEPDs alleviate stroke risks and neurocognitive outcomes after TAVI. We systematically searched MEDLINE, Scopus, Web of Science (WOS), and the Cochrane CENTRAL from inception until May 2025. We included randomized controlled trials (RCTs) that assessed the effectiveness of CEPD compared to the control group (no CEPD) in adult patients (> 18 years) undergoing TAVI. The primary endpoint was the incidence of all‐cause stroke. In contrast, the secondary endpoints included disabling stroke, systemic bleeding, transient ischemic attack (TIA), and major adverse cardiovascular and cerebrovascular events (MACCE). Additionally, we assessed neurological outcomes, including changes in the Montreal Cognitive Assessment (MoCA) score, the National Institutes of Health Stroke Scale (NIHSS) score, and the presence of new ischemic lesions. Nine RCTs comprising 11,696 patients were included in the final analysis. The use of CEPDs showed no statistical difference in reducing all‐cause stroke compared to the control group (OR = 0.91, 95% CI [0.73–1.15], p = 0.44). Additionally, there was no significant difference in other studies' secondary outcomes, including disabling stroke, MACCE, systemic bleeding, or neurological outcomes, such as worsening NISSS, decline in MoCA score, and the presence of new ischemic lesions. The use of CEPD during TAVI showed no benefit in reducing the risks of all‐cause stroke and other neurological outcomes studied.