Citations

Background and Aims: Sarcopenia (SP) is increasingly recognized as a poor prognostic factor for patients with Crohn’s disease (CD). We aimed to use radiographically-measured SP to determine a disease-specific definition and measure its association with CD-related outcomes. Methods: This retrospective study included adults with CD seen at our outpatient tertiary center between 2019 and 2021 who underwent a CT scan within 3 months of visit. Using axial cross-sectional measurements at the L3 vertebral level, skeletal muscle area was indexed to height to derive skeletal muscle index (SMI). Demographics, comorbidities, CD phenotype, and outcomes, including hospitalization at 1 year, were analyzed in univariate and multivariate models. Results: One hundred twenty-four patients with CD were included, with a mean age of 52.2±16.6 years and 53.2% (66/124) women. Overall, 33.1% (41/124) had SP based on sex-specific cutoffs with men representing 75.6% (31/41) of the sarcopenic population. In bivariate analysis, patients with SP had a higher likelihood of hospitalization (43.9% vs. 22.9% for non-SP, P =0.02) and penetrating CD phenotype (20.0% vs. 2.3% for non-SP, P <0.05). On multivariate regression, higher SMI was associated with decreased hospitalization, with each 10-unit increase in SMI conferring 0.54 lower odds (OR: 0.54 [95% CI: 0.32-0.92], P =0.02). Patients with higher SMI trended towards lower use of biologics (OR: 0.70 [95% CI: 0.45-1.09], P =0.12). Our novel SP definition derived from an IBD population performed similarly to definitions from the literature. Conclusion: Our study demonstrates the application of an automated algorithm for the quantification of body composition based on CT scan in patients with CD. SP and low SMI were associated with increased hospitalization at 1 year.

Abstract Background Prostate cancer is a heterogeneous disease comprising diverse cell types within the tumor microenvironment that support cancer cell survival. Using single cell and spatial transcriptomics, we previously identified subpopulations of treatment-persistent cancer cells exhibiting regenerative properties and a distinct molecular signature. Herein, we aimed to characterize the locked ‘Persist’ signature (PS) and its association with outcomes in a large cohort of non-metastatic prostate cancer tumors. Methods Patients with non-metastatic prostate cancer that underwent Decipher prostate genomic classifier and whole-transcriptome profiling on biopsy (BX, n=146,941) and radical prostatectomy (RP, n=55,329) specimens between October 2016 and February 2024 were included (Veracyte Inc., San Diego, CA, USA). Baseline clinical and pathological data from deidentified patients as well as signature scores were retrieved from the Decipher Genomic Resource for Intelligent Discovery (GRID) registry (Clinical Trials identifier: NCT02609269). The PS score based on the expression of 17 genes was calculated for all samples. Results PS was significantly associated with adverse clinical and pathological variables. In biopsy sample, PS was higher in cases with worse T3/4 clinical stage, Grade group (GG4-5), and high/very high NCCN risk (p&lt;0.001 for all). In RP sample, PS was significantly higher in patients with GG4-5, extraprostatic extension, seminal vesicle invasion and lymph node involvement (p&lt;0.001 for all). PS was also higher in patients with very high Decipher (&gt;0.85) in both BX and RP (p&lt;0.001 for both). When evaluating the prognosis of PS in multiple retrospective cohorts, PS in biopsy was prognostic of adverse pathology features at RP. PS was also prognostic of distance metastasis (DM) in multiple RP cohorts with long-term follow up (META855). In the ARNEO trial testing apalutamide in addition to ADT as neo-adjuvant treatment prior RP, PS was prognostic of early recurrence. In the Stampede trial, PS was prognostic of progression free survival, PCSM and OS in both non-metastatic and metastatic disease. When associating PS with other GRID signatures, PS was higher in samples with homologous recombination deficiency, TP53 mutations, Luminal B and luminal proliferating subtypes. On the other hand, PS was lower in samples with low androgen receptor-activity, RB-loss and neuroendocrine-like tumors. Finally, PS was positively correlated with radiation sensitivity signatures. Conclusions Persist is a novel molecular signature associated with more aggressive tumor characteristics. Future studies aim to further examine beyond this signature potential to identify patients at risk of aggressive prostate cancer, and understand what the optimal treatments for those with treatment-persistent prostate cancer cells are. Citation Format: Francesco Ballesio, Sinja Taavitsainen, Mohammed Alshalalfa, Antti Kiviaho, Mazlina Ismail, Reetta Nätkin, Alexander Giesen, Thomas Munro, James A. Proudfoot, Hyunnam Ryu, Elai Davicioni, Matthew C. Cooperberg, R. Jeffrey. Karnes, Ruochen Jiang, Steven Joniau, Gerhardt Attard, Frank Claessens, Matti Nykter, Alfonso Urbanucci. Persist: a molecular signature for prostate cancer patients with preexisting treatment-persistent cells associated with aggressive disease [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Innovations in Prostate Cancer Research and Treatment; 2026 Jan 20-22; Philadelphia PA. Philadelphia (PA): AACR; Cancer Res 2026;86(2_Suppl):Abstract nr B079.

Abstract Background Measurement of cardiac troponin (cTn) using high-sensitivity assays is recommended for the diagnosis of myocardial infarction. We determined sex-specific and uniform 99th percentile upper reference limits (URLs) using the new Elecsys® Troponin T high-sensitivity Gen 6 assay in a global, healthy reference range cohort. Methods Lithium-heparin plasma and serum samples were prospectively collected from apparently healthy individuals aged ≥20 years across 34 global sites in the United States, Europe, China, and Japan. cTnT was measured using the Troponin T high-sensitivity Gen 6 assay on the Cobas® e 801 analyzer. Exclusion criteria were defined according to the 2022 IFCC guidance. Uniform and sex-specific 99th percentile URLs and nonparametric 95% CIs were determined in plasma and serum separately and combined. Results The final study population comprised 4147 participants (52.5% female) with a median (25th–75th percentiles) age of 48.0 (33.0–59.0) years; 45.8%, 47.9%, 5.2%, and 1.1% were White, Asian, Black, and other/unknown, respectively. For sample matrices combined (n = 8294), 81.0% and 99.2% of cTnT values were above the limit of detection in females and males, respectively. Sex-specific 99th percentile URLs (95% CI) were 18 (16–23) ng/L for females and 32 (28–35) ng/L for males; the uniform 99th percentile URL was 27 (24–31) ng/L. URLs were comparable in plasma and serum samples. Conclusions This study determined sex-specific and uniform 99th percentile URLs for the Troponin T high-sensitivity Gen 6 assay that were comparable irrespective of the matrix used in a large, global, healthy reference population.

Abstract Object Transdermal biosensors may provide an alternative to conventional blood-based biomarker measurement. Our purpose was to determine the binary correlation between transdermal (Infrasensor™; RCE, Inc, Carlsbad, CA) and conventional blood-based measurements. Methods This was a secondary analysis from a previously published observational cardiac troponin I (cTnI) study performed to establish the upper reference level of cTnI, at 10 US hospitals. After obtaining informed consent, 2 cohorts of patients were enrolled: 1) those who completed a health assessment questionnaire and appeared healthy, and 2) those with a known elevated cTnI per the local hospital standard assay. All blood lab analyses were performed at the University of Maryland Medical Center, Baltimore, MD. Normal was defined as cTnI <53.48 ng/L (male) or 34.11 ng/L (female) using the Siemens Atellica IM assay (Siemens Medical Solutions, Mountain View, CA), NT-proBNP <450 pg/mL (>75 years) or <124 pg/mL (<75 years), creatinine >1.17 mg/dL (male) or >0.95 mg/dL (female), and HbA1c <6.4%. The Infrasensor was placed on the patient’s wrist for measurement and blood drawn for analysis at approximately the same time. Results Of 840 enrolled patients, the median (IQR) age was 46 (30,57), 416 (49.5%) were female, 10.36% Hispanic, 6.7% Asian, 12.9% African American, and 69.1% White. Elevated lab tests were 102 hscTnI’s, 156 NTproBNP’s, 37 HbA1C’s, and 163 creatinine’s. Significant binary correlations were found between all transdermal signals and the corresponding lab blood levels Conclusion Infrasensor transcutaneous measurement demonstrates similar results as that obtained from blood testing in the central laboratory. Capsule The Infrasensor (RCE, Inc, Carlsbad, CA, USA) is rapid point of care transcutaneous biomarker measurement device. This study evaluated its ability to provide qualitative results for troponin I, NTproBNP, creatinine, and HbA1c levels in 840 patients. Significant correlations were found between all transdermal signals and the corresponding binary lab blood levels.

103 Background: Clinicians spend significant time extracting and synthesizing information to risk-stratify and make adjuvant chemotherapy (AC) recommendations for CRC. By automating parts of this process, LLMs could help reduce documentation burden and variability in decision-making. Methods: We selected 144 stage III, pMMR CRC patients treated at Mayo Clinic (2017–2021). HIPAA-compliant Gemini-2.0-Flash-001 and GPT-4o extracted clinical variables (age, neuropathy grade, pathological stage) from EHRs and generated AC recommendations. Two approaches were compared: (1) a rule-based algorithm with nested if/else statements translating variables into NCCN-based recommendations, and (2) a dynamic LLM agent generating recommendations using a structured prompt informed by NCCN guidelines. Concordance with treating physicians was assessed, with disagreements reviewed by a blinded GI oncologist. Results: The dataset included 144 patients with median age 67 (IQR 66–68), 48.6% female. The LLM pipeline extracted neuropathy grade with 100% accuracy and pathological T/N stages with 99.3% accuracy. Concordance with physician recommendations was 93.1% for the rule-based algorithm and 62.5% for the LLM agent. In discordant cases, blinded adjudication by a GI oncologist favored the algorithm and LLM agent over physicians in most cases (Table 1). Conclusions: This exploratory work shows LLM agents can reliably extract variables and generate evidence-based treatment recommendations for stage III CRC. The high rate of expert preference for LLM recommendations in discordant cases is intriguing but limited by small sample size and possible adjudicator bias. Discordant physician recommendations reflect the complexity of decision-making, including patient preferences, performance status, comorbidities, and subtle findings not fully captured in EHRs. Rather than replacing judgment, we envision LLMs as decision support tools—analogous to an advanced trainee reviewing charts and presenting evidence-based recommendations to the attending physician with ultimate authority. Larger multi-institutional studies with multiple adjudicators are needed to validate these findings and clarify AI’s role in oncology. Patient characteristics, LLM extraction accuracy, and concordance with physician recommendations. Metric Result Total patients 144 Median age (IQR) 67 (66-68) Female (%) 48.6% LLM extraction accuracy – Neuropathy grade 100% LLM extraction accuracy – Pathological T and N stages 99.3% Primary Concordance – Rule-based algorithm vs. physician 93.1% Adjudicator preference of rule-based algorithm over treating physician for discordant cases 100% Concordance – LLM agent vs. physician 62.5% Adjudicator preference of LLM agent over treating physician for discordant cases 82.0%

ABSTRACT Obstructive sleep apnea (OSA) is a common, heritable disorder with diverse clinical presentations and etiologies. We conducted a genome-wide association meta-analysis of 492,107 individuals, including 46,028 OSA cases, identifying 14 genome-wide significant loci, eight of which are novel. Analyses adjusting for body mass index (BMI) revealed three loci independent of obesity, implicating alternative biological pathways contributing to disease. Integrative functional analyses, including chromatin interaction mapping, fine-mapping, and eQTL colocalization, prioritized candidate effector genes. Notably, implicated genes in chondrocytes were associated with craniofacial morphology in both mouse and human multivariate genotype-phenotype mapping, supporting a role for craniofacial structure in OSA risk. These findings highlight key genetic pathways (obesity-related, neurological, and craniofacial) underlying the development of OSA, offering new insights into its complex etiology.

We present a subset analysis on the adolescent cohort of the S1826 randomized phase three trial, comparing nivolumab, doxorubicin, vinblastine, dacarbazine (N-AVD) to brentuximab vedotin-AVD (BV-AVD) in newly diagnosed advanced-stage (AS, stages III and IV) classic Hodgkin lymphoma (cHL). Among 994 patients enrolled, 24% (n = 240) were age 12-17 years. The 3-year progression-free survival (PFS) was significantly higher in the N-AVD group (93% [95% CI, 87 to 96]) compared with the BV-AVD group (82% [95% CI, 73 to 88]; hazard ratio, 0.37 [95% CI, 0.17 to 0.80]). One N-AVD and two BV-AVD patients received protocol-specified residual site radiotherapy (RT). Rates of febrile neutropenia and sepsis were low in both groups. Severe immune-related adverse events were infrequent, although thyroid dysfunction was seen in 7% with N-AVD. Sensory neuropathy (grade ≥2) was more frequent with BV-AVD (14% v 7%) by clinician report. Although premature discontinuation of therapy was reported in 12 N-AVD patients and four BV-AVD patients, no PFS events were noted in the N-AVD group. Patient-reported outcomes indicated less toxicity with N-AVD. N-AVD demonstrated high 3-year PFS in adolescents with AS cHL, with minimal RT use. S1826 exemplifies the benefits of harmonized clinical trial protocols, resulting in timely access to novel agents for adolescents.

BACKGROUND: The Ventral Rectopexy International Expert Panel recently published a consensus update on ventral rectopexy. The ability of large language models to synthesize the literature on ventral rectopexy without an explicit knowledge base was studied before the publication of the consensus. OBJECTIVE: To compare the responses and citations of different large language models on ventral rectopexy using the expert panel consensus as the reference standard. DESIGN: ChatGPT-4o, Gemini 1.5 Pro, and OpenEvidence were compared on content appropriateness (1 = inappropriate to 5 = appropriate), readability (Flesch reading ease), response length, citation fabrication, and citation quality per Oxford Levels of Evidence. The most content-appropriate chatbot response selected by the expert panel was de-identified and presented alongside the consensus text to 15 colorectal surgeons who attempted to identify the chatbot-generated text. SETTINGS: Questions were submitted from September 18 to 19, 2024. Analysis was performed before the online publication of the consensus on January 30, 2025. MAIN OUTCOME MEASURES: The main outcome measures included content appropriateness, fabricated citation rate, citation quality, and the accuracy of identifying human versus chatbot text by colorectal surgeons. RESULTS: OpenEvidence ranked highest for content appropriateness (mean 3.5/5), above Gemini (3.0/5) and ChatGPT (2.8/5; p < 0.001). ChatGPT was most verbose with the highest readability scores ( p = 0.021). ChatGPT fabricated 53% of citations; Gemini fabricated 12%; OpenEvidence fabricated 0% ( p < 0.001). All OpenEvidence citations were peer reviewed, with 40 of 117 (34%) citing level I to III studies compared with 46 of 94 (49%) of the references cited in the consensus ( p = 0.043). Chatbot-generated responses were identified with 28 of 51 (55%) accuracy. LIMITATIONS: Reproducibility may be affected due to the nature of large language models and the availability of the consensus after publication. CONCLUSIONS: OpenEvidence outperformed Gemini 1.5 Pro and ChatGPT-4o in content appropriateness and peer-reviewed citation quantity and quality. Chatbot-generated text was indistinguishable from expert-authored consensus to subject matter experts. Large language models, as an early-stage research tool, may be viable for future consensus working groups, provided transparent disclosure and rigorous oversight. See Video Abstract . ¿PUEDEN LOS MODELOS LINGÜÍSTICOS DE GRAN TAMAÑO SER UNA HERRAMIENTA VIABLE PARA LOS GRUPOS DE TRABAJO DE CONSENSO? LA EXPERIENCIA DEL GRUPO DE CONSENSO DE EXPERTOS EN RECTOPEXIA VENTRAL ANTECEDENTES: El Panel Internacional de Expertos en Rectopexia Ventral publicó recientemente una actualización consensuada sobre la rectopexia ventral. Antes de la publicación del consenso, se estudió la capacidad de los grandes modelos lingüísticos para sintetizar la bibliografía sobre la rectopexia ventral sin una base de conocimientos explícita. Objetivo: Comparar las respuestas y citas de diferentes grandes modelos lingüísticos sobre la rectopexia ventral utilizando el consenso del panel de expertos como estándar de referencia. DISEÑO: Se compararon ChatGPT-4o, Gemini 1.5 Pro y OpenEvidence en cuanto a la idoneidad del contenido (1 = inadecuado a 5 = adecuado), la legibilidad (índice de legibilidad de Flesch), la longitud de la respuesta, la fabricación de citas y la calidad de las citas según los niveles de evidencia de Oxford. La respuesta del chatbot más adecuada en cuanto al contenido seleccionada por el panel de expertos se anonimizó y se presentó junto con el texto del consenso a 15 cirujanos colorrectales que intentaron identificar el texto generado por el chatbot. ENTORNO: Las preguntas se enviaron los días 18 y 19 de septiembre de 2024. El análisis se realizó antes de la publicación del consenso en línea el 30 de enero de 2025. PRINCIPALES MEDIDAS DE RESULTADOS: Adecuación del contenido, tasa de citas inventadas, calidad de las citas, precisión en la identificación del texto humano frente al del chatbot por parte de los cirujanos colorrectales. RESULTADOS: OpenEvidence obtuvo la puntuación más alta en cuanto a la adecuación del contenido (media de 3,5/5), por encima de Gemini (3,0/5) y ChatGPT (2,8/5) (p<0,001). ChatGPT fue el más prolijo, con las puntuaciones más altas en legibilidad (p = 0,021). ChatGPT inventó el 53% de las citas; Gemini inventó el 12 %; OpenEvidence inventó el 0 % (p < 0,001). Todas las citas de OpenEvidence fueron revisadas por pares, con 40/117 (34 %) que citaban estudios de nivel I-III frente a 46/94 (49 %) de las referencias citadas en el consenso (p = 0,043). Las respuestas generadas por el chatbot se identificaron con una precisión del 28/51 (55 %). LIMITACIONES: Reproducibilidad debido a la naturaleza de los modelos de lenguaje grandes y a la disponibilidad del consenso tras la publicación. CONCLUSIONES: OpenEvidence superó a Gemini 1.5 Pro y ChatGPT-4o en cuanto a la idoneidad del contenido y la cantidad y calidad de las citas revisadas por pares. El texto generado por el chatbot era indistinguible del consenso redactado por expertos para los expertos en la materia. Los modelos de lenguaje grandes como herramienta de investigación en fase inicial pueden ser viables para futuros grupos de trabajo de consenso, siempre que se garantice una divulgación transparente y una supervisión rigurosa. ( AI-generated translation )

Abstract Background Red blood cell (RBC) transfusion may be lifesaving, however transfusion-transmitted infections (TTI) and transfusion-associated graft-versus-host disease (TA-GVHD) still pose a threat despite current donor selection and testing requirements. Amustaline (S-303)/glutathione (GSH) pathogen reduction (PR) is designed to inactivate infectious microbes and leukocytes in RBCs. The RedeS study evaluates the safety and efficacy of amustaline/GSH PR-RBCs compared to conventional RBCs in a broad spectrum of patients requiring acute and/or repeated RBC transfusion support. Methods RedeS is a Phase 3, prospective, multi-center, randomized, double-blind, active-controlled, parallel-design study, with a 6-month extension option to evaluate patients requiring repeated transfusions including red cell exchange (RCE).Eligible subjects will be stratified according to site, baseline bleeding status and participation in the extension period. The study arms include a transfusion period of 28-days for anemia with any bleeding or non-bleeding patients or a 28-day+6-month extension for non-bleeding patients with chronic anemia requiring repeated simple transfusions, or for patients with sickle cell disease (SCD) expected to receive three RCE procedures. The study will seek to enroll 600-800 subjects in the overall safety analysis, including ~140 repeatedly-transfused subjects in the 6-month extension including up to 30 subjects receiving three RCE procedures. The primary safety endpoints are the proportion of patients with any treatment-emergent adverse events (TEAEs) related to study RBC transfusion through 28 days after the last study transfusion, and the proportion of patients with treatment-emergent antibodies with confirmed specificity to PR-RBCs. The primary efficacy endpoint is the hemoglobin (Hb) increment in subjects who are non-bleeding at baseline, adjusted for the grams of Hb transfused and averaged over multiple transfusions. With 352 evaluable transfused non-bleeding subjects (176 per treatment group) from either arm, the study will have 80% power to demonstrate non-inferiority, defined as a Hb increment treatment difference of no more than 15% of the Control group mean, assuming a Control arm coefficient of variation of 50%. Discussion RedeS will characterize the safety of amustaline/GSH PR-RBCs and is designed to demonstrate the non-inferiority of PR-RBCs to conventional RBCs with respect to Hb increment, a common pragmatic clinical assessment of RBC transfusion effectiveness.