Citations

Abstract Background Substituting group A whole blood (GAWB) might relieve some of the burden on the low titer group O whole blood (LTOWB) inventory. This simulation examined the effect of implementing GAWB at a large trauma hospital. Study Design and Methods A civilian trauma center with LTOWB and GAWB par levels set to 22 and 10 units, respectively, was modeled as the baseline. The average daily number of WB recipients was 0.5 who received an average of four WB units per patient. LTOWB was issued in packages of five and all had to be consumed before a group A patient could be switched to GAWB. Several variations on the baseline simulation were also modeled. Results In the baseline simulation, there was a median (interquartile range, IQR) of 1 (0–2) GAWB and 16 (13–19) LTOWB recipients per month. The median (IQR) GAWB and LTOWB units transfused per month was 2 (0–9) and 56 (42–72), respectively. Fourteen percent of group A patients received any quantity of GAWB. The variations that had the most impact on GAWB usage included increasing the number of WB recipients to 2.5 per day where the median (IQR) monthly number of GAWB recipients and units transfused increased to 4 (3–5) recipients and 21 (12–29) units, respectively, and when the average WB requirements increased to eight units per patient resulting in transfusing a median (IQR) of 10 (5–15) GAWB units per month to 3 (1–4) recipients. Discussion Under routine civilian hospital circumstances, implementing GAWB will have a modest impact on LTOWB inventory.

Background: The most critical exam components in patients seeking rhinoplasty have not been established. Objective: To identify concordance among experienced rhinoplasty surgeons regarding the most important exam features for various deformities. Methods: An online questionnaire was distributed to board-certified facial plastic and plastic surgeons experienced in rhinoplasty, with seven nasal deformity categories: dorsal hump, crooked nose, boxy tip, pinched tip, droopy tip, saddle nose, and nonallergic nasal obstruction. For each, respondents were asked to rank the three most important anatomic regions to examine from the following: nasal bones, midvault cartilage, skin, radix, facial profile, lip, tip, septum, internal nasal valve, nostrils, inferior and middle turbinates. For each ranked region, up to three important features were chosen. Normalized Attention Scores (NAS) were calculated to determine agreement amongst surgeons. Results: A total of 13 facial plastic and 8 plastic surgeons were invited to participate and completed the questionnaire. All cases had high agreement demonstrated by NAS, with the dorsal hump case exhibiting the greatest variability in responses. Conclusions: In this survey of 21 rhinoplasty surgeons, there was general agreement regarding the most relevant anatomical structures and features, which may provide a conceptual foundation for identifying key exam features for seven common complaints in patients seeking rhinoplasty.

Abstract Inherited susceptibility plays a critical role in prostate cancer (PCa) risk. Using large biobank and case-control datasets, we evaluated the contribution of both common variants and rare germline pathogenic variants (PVs) to overall PCa risk. The Prostate Cancer Exome Sequencing Consortium currently includes 427,388 male participants (51,452 PCa cases and 375,936 controls) with whole-exome sequencing data from ten biobanks and studies: UK Biobank (14,669 cases/195,600 controls), All of Us Research Program (7,577/75,226), African Ancestry Prostate Cancer Consortium (7,176/4,675), Mayo Clinic Biobank (6,031/15,084), Mass General Brigham Biobank (3,393/14,095), Geisinger’s MyCode Community Health Initiative (3,026/15,130), UCLA ATLAS Precision Medicine Biobank (2,850/16,904), Penn Medicine Biobank (2,598/16,255), Colorado Center for Personalized Medicine (2,269/13,399), and Malmo Diet and Cancer (1,863/9,568). Based on self-reported race/ethnicity and estimated genetic ancestry, the cases comprise approximately 79% European, 18% African, and 3% other ancestry populations. Single-variant association analyses tested all variants on chromosomes 1-22 and X with a minor allele count ≥ 5. In gene-based analyses, PVs were defined as rare variants (minor allele frequency [MAF] < 1% in controls) that had either a Variant Effect Predictor (VEP) impact score of “high” or a pathogenic or likely pathogenic ClinVar classification. Associations were estimated using Firth logistic regression, adjusting for age and the top ten genetic principal components. Results from individual studies were combined using fixed-effect meta-analysis. In single-variant association analyses, 496 variants reached genome-wide significance (p<5×10-8; MAF>0.02%). Among these, 458 (92%) variants mapped to previously known risk regions, including three rare PVs in HOXB13 (rs138213197), CHEK2 (rs555607708), and FAM111A (rs533676902). Characterization of the remaining 38 variants is ongoing. Gene-based analyses identified significant associations (p<2.4×10-6) for eight genes: HOXB13 (OR=3.7, 95% CI=3.3-4.2), BRCA2 (OR=2.0, 95% CI=1.7-2.3), CHEK2 (OR=1.6, 95% CI=1.5-1.8), ATM (OR=1.6, 95% CI=1.4-1.9), FAM111A (OR=1.4, 95% CI=1.3-1.5), BIK (OR=1.4, 95% CI=1.2-1.6), SAMHD1 (OR=2.1, 95% CI=1.6-2.7), and SMOC2 (OR=3.2, 95% CI=2.0-5.1). All genes except SMOC2 have been previously implicated in PCa susceptibility. Among cancer predisposition and DNA repair genes, nominal associations were also observed for XRCC2 (OR=1.6, 95% CIs=1.2-2.3) and BRCA1 (OR=1.2, 95% CI=1.0-1.4), whereas the association was not significant for PALB2 (OR=1.2, 95% CI=0.9-1.5). These findings reinforce the role of rare germline PVs, particularly in cancer predisposition and DNA repair genes, in PCa susceptibility. As additional studies are incorporated into the Consortium, we expect this work to provide a more comprehensive characterization of the genetic architecture of PCa. Citation Format: Yifan Zhang, Shuyan Cheng, Nicholas Boddicker, Matthew Lebo, Alexander S. Berry, Roni Haas, Ryan Hausler, Tokhir Dadaev, Heena Desai, Alex A. Rodriguez, Ravi K. Madduri, Andrew Hill, Xin Sheng, Susan M. Gundell, Mine Cicek, Penn Medicine Biobank, Olle Melander, Chris R. Gignoux, Isla P. Garraway, Bogdan Pasaniuc, Paul C. Boutros, Matt Oetjens, Adam S. Kibel, Robert J. Klein, Zsofia Kote-Jarai, Fergus J. Couch, Kara N. Maxwell, Burcu F. Darst, David V. Conti, Christopher A. Haiman, Fei Chen. Genetic risk of prostate cancer: Insights from the Prostate Cancer Sequencing Consortium [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(8_Suppl):Abstract nr LB390.

Abstract Introduction: Epoxy fatty acid (EpFA) mechanisms of hormone therapy resistance (HTR) in ER+HER2- breast cancer (BC) are poorly understood. EETs are EpFAs that contribute to BC progression and HTR by promoting oxidative phosphorylation (OXPHOS). However, it remains unclear how EETs contribute to HTR. In this study, two fulvestrant resistant (FR) subclones of the letrozole resistant (LR) MCF-7AC1 line were isolated (termed LR/FR) and were incidentally resistant to the CDKi palbociclib (PR) (termed MCF-7AC1 LR/FR/PR or multiply resistant - MCF-7AC1 MR). These HTR cell lines exhibited CYP3A4 upregulation (2.3- to 4.3-fold) and increased cellular (±)14,15-EET levels, which were suppressed by biguanide treatment (P<0.05). Structure activity studies led to the design of hexyl cuban-1-yl biguanide (HCB) and fluorinated HCB derivatives C5F2-HCB and C6F3-HCB, which inhibited CYP3A4-mediated EET biosynthesis and growth of the HTR lines. HCB fluorination improved pharmacokinetics (PK) and toxicity. Methods: HCB and fluorinated HCBs were tested for impact on EET biosynthesis, OXPHOS, PK, and growth inhibition and reversal of hypoxia in the MCF-7AC1 MR tumor model. Results: Fulvestrant selection for MCF-7AC1 MR cell lines resulted in undetectable cyclin D1 and estrogen receptor (ERα) expression, while cyclin E1, CDK4, CDK6, CYP3A4, and c-MYC were upregulated (P<0.001). MCF-7 MR cells demonstrated 1.8, 1.4, and 1.2- fold higher levels of (±)8,9, (±)11,12, and (±)14,15-EET compared to parental MCF-7 cells (P<0.05). The most potent fluorinated HCB, C6F3-HCB, suppressed cellular levels of (±)8,9-EET, (±)11,12-EET, and (±)14,15-EET by 53-60% (P<0.029). The MCF-7AC1 MR cells were more potently inhibited by HCBs and fluorinated derivatives compared to the MCF-7 cell line. Comparing an MCF-7 MR line vs. MCF-7, HCB exhibited IC50 values of 4.1 vs. 7.0 uM, C5F2-HCB 10 vs. 25 uM, and C6F3-HCB 5.4 vs. 12 uM (P values all <0.05). C5F2-HCB exhibited the best PK and treatment of the MCF-7AC1 MR xenograft model showed reversal of hypoxia (P<0.05) and transient inhibition by C5F2-HCB (P=0.025 at 20 days). P/F also transiently inhibited this model (P=0.006 at 20 days). C5F2-HCB and P/F showed synergy in vitro (CI=0.46) leading to testing of C5F2-HCB/P/F in vivo enabled by acceptable toxicity of the triplet in mice. This combination showed synergy in vivo vs. standard of care palbociclib/fulvestrant by nonparametric statistical tests (Mann Whitney; P=0.0389; Kolmogorov-Smirnov; P=0.0473), providing a pathway for possible clinical development of the combination. Conclusions: MR BC cell lines exhibit upregulation of CYP3A4 and biosynthesis of EETs, indicating a role for EETs in HTR. The C5F2-HCB/P/F exhibits activity against the highly resistant MCF-7 MR xenograft with acceptable toxicity indicating an avenue for clinical development. Citation Format: Zhijun Guo, Jianxun Lei, Christian T. Wells, Allison M. Makovec, Andrew C. Yates, Swaathi Jayaraman, John R. Hawse, Joshua A. McCarra, Qing Cao, Michael J. Pryzbilla, Brenda L. Koniar, Beverly J. Norris, Craig M. Florey, Robert J. Schumacher, Michael A. Farrar, Kaylee L. Schwertfeger, Elizabeth A. Ambrose, Henry Wong, Gunda I. Georg, Antonino D'Assoro, Matthew P. Goetz, David A. Potter. Fluorinated cuban-1-yl biguanides overcome hormone therapy resistance to standard of care fulvestrant, and palbociclib [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(8_Suppl):Abstract nr LB196.

Abstract Background: Black men experience the highest burden of prostate cancer (CaP) incidence and mortality in the United States. The reasons documented for the significant burden of CaP in Black communities include health systems, care process, and individual/personal level factors, such as cultural factors, psychosocial factors, decision making/preferences, comprehension, past experience, and perceived behavioral control. The Community Living Lab (CoLLab) Learning Health System (LHS) was established within three American Legion Posts (ALP) in Northeast Florida to address these factors. Study Objective: This clinical trial study evaluated the impact of the CoLLab LHS on the knowledge, attitudes, beliefs, and cues to action of Black men who received Resources, Education, Amenities, and Community Health (REACH) services at the ALPs. Methods: The design was guided by the Intervention Mapping Framework and the Social Ecological Model. CoLLab REACH services were made available to participants through trusted community infrastructures. Services integrated include CaP resources and materials, social determinant of health navigation, healthy grocery distribution, cancer advocacy programs, and research participation. Participants were recruited at three ALPs and were asked to visit their respective CoLLab LHS site at least twice a month and up to 24 times over one year to use any of the services. The impact was measured using baseline and quarterly surveys assessing CaP awareness, knowledge, attitude, health beliefs, perceived control, intentions, and cues to action. Descriptive statistics were used to compare participants' information at baseline and at 3-month follow-up. Results: A total of 173 participants were included in this analysis; 57.9% were ≥ 60 years, and 92.2% were US-born Black men. Prostate cancer knowledge increased from baseline to 3-month follow-up. The median score rose from 4±1.29 at baseline, with the mean increasing to 4.24±1.10. Attitudes towards Cap screening declined marginally from 12.58±2.15 to 12.27±2.40. Health beliefs showed a clear upward shift, with the mean increasing from 22.86±3.0 at baseline to 23.20±2.82 after 3 months of intervention. Additionally, cues to action also improved, with the mean increasing from 2.78±1.67 to 3.25±1.45. Only the cues-to-action index showed a statistically significant difference (p = 0.018), with higher scores observed after 3 months of intervention. Conclusion: Across the four core constructs—prostate cancer knowledge, testing attitudes, health beliefs, and cues to action—outcomes at follow-up demonstrated modest but consistent improvements compared to those of baseline, alongside slightly reduced variability for most domains. Overall, the evaluation showed that CoLLab REACH services improved knowledge, enhanced stronger health beliefs, and significantly increased cues to action, while testing attitudes remained comparatively stable. Citation Format: Folakemi T. Odedina, Opeyemi Oreoluwa Bolajoko, Quincy A. Wimberly, Daniel W. Lee, Floyd B. Willis, Toshiko Moultrie, Wayne Ford, Derry Green, Arnold J. Merriweather, Michelle Fudge. The impact of the Community Living Lab learning health system on the prostate cancer knowledge, attitudes, beliefs, and cues to action of Black men [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(8_Suppl):Abstract nr LB324.

Abstract Real-time, proactive detection has become a necessity as health systems face converging pressures that legacy tools cannot solve: rising acuity, workforce strain, and persistent quality gaps that erode margins, capacity, and reputation. Clinical decision support has historically lagged because rudimentary rules-based systems drown clinicians in false alerts, eroding trust without reliably changing outcomes at the bedside. Bayesian Health’s real-time clinical intelligence platform was built to close this gap by continuously synthesizing multimodal EHR data (vitals, labs, medications, procedures, and longitudinal history) to learn patient-specific baselines and surface only the most actionable, high-precision signals to care teams. Across diverse health systems, this platform has been used to enable earlier recognition and intervention for a range of high-impact conditions, improving both bedside care and system performance. This talk will focus on concrete, real-world applications of the platform for sepsis, clinical deterioration, and palliative care needs, illustrating how earlier detection and workflow-integrated interventions drive measurable gains in clinical outcomes and margins, and why the value of early, precise detection is amplified in high-risk populations such as oncology patients, whose higher baseline acuity and treatment-related toxicities both elevate their risk of harm and make emerging deterioration harder to recognize. Case Study: Detecting Sepsis within a Oncology Patient Subpopulation. Background: Sepsis remains one of the leading causes of in-hospital mortality, and traditional rules-based alerts have struggled to deliver timely, actionable detection without overwhelming clinicians with false alarms. Oncology patients experience an elevated risk for sepsis and septic shock, and those who experience sepsis are more likely to suffer in-hospital mortality than non-cancer patients with sepsis. Early recognition of sepsis onset is challenging due to the overlap between signs of sepsis and inflammation and tumor- and treatment-related toxicities. We investigated the ability of Bayesian Health’s real-time artificial intelligence-based computational algorithm to perform timely detection of sepsis onset in hospitalized patients with cancer. This algorithm ingests data directly from the electronic health record, such as vital signs, laboratory results, medications, procedures, and patient-specific historical results, processing it in a continuous manner to flag presence of sepsis as early as possible. Methods: Analysis included 7480 adult emergency and inpatient encounters from three tertiary and quaternary academic centers (Cleveland Clinic Main Campus, Sinai Hospital of Baltimore, and Strong Memorial Hospital) and one community hospital (Cleveland Clinic Fairview Hospital) with sufficient data for inclusion (age ≥ 18, presence in an emergency or inpatient care unit, and at least one measurement of a panel of vital signs). Patients with cancer (including subgroups of solid tumor and hematologic malignancy) were identified by current or past recorded diagnoses (ICD-10 codes). All included patient records underwent a multi-tiered retrospective adjudication process. An automated screen labeled records with no evidence of infection or organ dysfunction as non-sepsis, removing them from need for manual review. Two independent physicians then adjudicated a sample of the eliminated records in addition to each remaining record for both presence of sepsis and time of onset, with a third physician reconciling disagreements. Evaluation of the algorithm included all discrete flags generated by the system during a period of time it was not in clinical use and not visible to care teams. Results: In the overall population, 3.1% of all patients and 6.0% of cancer patients were adjudicated to have had sepsis, including zero from a sample of 200 of the records marked as non-sepsis in automated screening. The detection algorithm identified sepsis with high and consistent accuracy across all patients and across cancer patients, including those with solid tumors and with hematologic malignancies (Table). A flag for sepsis occurred in 85.8% of all sepsis patients and 86.1% of cancer patients with sepsis within 4 days of sepsis onset. Sepsis was present in 24.2% of all cancer patients flagged (22.9% of solid tumor patients and 27.9% of hematologic malignancy patients). Compared to patients who were never flagged, all patients who were flagged, whether they had sepsis or not, were more likely to experience in-hospital mortality (7.9% vs 0.3%, p < 0.001) or ICU transfer (38.2% vs 7.9%, p < 0.001). This was also true within oncology patients (in-hospital mortality: 8.8% vs 0.4%, p < 0.001; ICU transfer: 34.7% vs 9.7%, p < 0.001). Implementation of an automated sepsis detection system with high accuracy in populations such as cancer patients, who have elevated risk of poor outcomes following sepsis, provides an opportunity to meaningfully improve timely delivery of care and reduce subsequent morbidity and mortality while minimizing alert fatigue for clinicians. Citation Format: Suchi Saria, Varesh Prasad, Nicasia Beebe-Wang, Ellie Zhang, Neri Cohen, David Graham, Conrad Gleber, James Morrison, Jacob Strand, Alexandra Tallman. Real-time multimodal AI enables individualized care in challenging subpopulations [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(8_Suppl):Abstract nr PL03-03.