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(335) The Gamut of Gamete Retrieval Methods: Male Fertility Preservation Practices Among Reproductive Urologists
Naelitz, Bryan D. , Momtazi-Mar, L , Khoei, A, Hussain, Bilal , Jeffrey, John J., Dabaja, Ali , Lundy, S, Consoritum, M, Hussain, B, Jeffrey, J, Nam, C, Punjani, Nahid

The Journal of Sexual Medicine | December 9, 2025 | Volume: 22 | Issue: Supplement_4 | Pages: No page available

10.1093/jsxmed/qdaf320.330 Get It

Abstract Introduction There is wide variation in male fertility preservation practices. While physician preference accounts for some of this diversity, practice patterns often reflect multiple extrinsic factors including patient demographics, equipment availability, laboratory protocols, and state law. Objective We sought to characterize national trends in sperm retrieval and storage across reproductive urology practices in the United States. Methods An anonymous 34-item survey characterizing provider demographics, practice settings, fertility preservation procedures, andrology laboratory practices, and cryopreservation expenses was designed. Practicing reproductive urologists were identified using information available through professional societies. Our survey was constructed using the Qualtrics platform and distributed electronically between October 2024 and May 2025. Results 39 responses were received by urologists practicing across 21 states (response rate: 21%, n=189). A majority (74%, n=29) of survey responders practiced at academic medical centers, with others practicing at non-academic hospitals (8%, n=3) and private practices (13%, n=5). The most common indications for fertility preservation reported included oncologic care (42%), gamete storage for planned ART (31%), transgender care (18%), pre-vasectomy sperm banking (10%), and pre-deployment banking for military personnel (5%). Nearly all providers performed microsurgical sperm retrievals (97%, n=38, Figure) and oncologic testicular sperm extractions (85%, n=33) when indicated. More than half of providers offered conventional testicular sperm extractions (72%, n=28), microsurgical epididymal sperm aspirations (59%, n=23), testicular sperm aspirations (56%, n=22), penile vibratory stimulation (54%, n=21), or percutaneous epididymal sperm aspirations (52%, n=20). Fewer providers offered post-mortem sperm retrieval (49%, n=19), pre-pubertal testicular tissue cryopreservation (36%, n=14), or electroejaculation (31%, n=12). Most respondents (62%, n=24) had access to an on-site andrology laboratory. Semen analyses were evaluated using manual (53%, n=20), computer-assisted (11%, n=4), or combinatorial methods (26%, n=10). Though many (37%, n=14) providers were uncertain about institutional costs for semen specimen processing, a plurality of respondents (40%, n=15) reported fees ranging from $100-500 with the remainder (23%, n=9) reporting fees exceeding $500. Respondents most frequently reported semen storage fees ranging between $100-300 per year (39%, n=15), while approximately a third (31%, n=12) estimated these costs to range between $300-600 per year. However, 18% (n=7) of respondents reported higher costs for specimen storage and 13% (n=5) were uncertain about the expense of this service. Conclusions This multi-institutional, geographically diverse survey reveals significant variation in reproductive urology practice patterns and cost associated with semen analyses and storage. Future studies will explore differences in practice patterns to better understand the factors influencing this variation and their effect on male reproductive healthcare. In the absence of society guidelines, reproductive urologists must collaborate, share best practices, and maintain price transparency to ensure sperm retrieval remains accessible and affordable. Disclosure No
(041) Female Partner Attitudes and Beliefs Regarding Penile Implant Surgery: A Qualitative Analysis
Nappo, V, Salter, Charles A., Thorogood, Samantha L., Gilliland, Jaime , Atkinson, Thomas M. , Liso, Nicole, Helo, S, Flores, José , Mulhall, John P. , Salter, C, Kim, D, Nelson, Christian J. , Helo, S

The Journal of Sexual Medicine | December 9, 2025 | Volume: 22 | Issue: Supplement_4 | Pages: No page available

10.1093/jsxmed/qdaf320.041 Get It

Abstract Introduction Penile implant (PI) surgery is a well-recognized strategy for erectile dysfunction (ED) with excellent functional/satisfaction outcomes. To date, little attention has been paid to the attitudes and satisfaction outcomes of female partners of such patients. Objective To qualitatively assess how female partners feel about PI surgery to inform the development of a female partner specific questionnaire. Methods Female partners of men who had undergone PI surgery (3-piece inflatable) underwent concept elicitation interviews. Prior to this, a panel of experts in female sexual health and PI surgery was convened to define potential domains of interest. Women were interviewed by one of two female sexual medicine clinicians to elicit concepts. As part of the spontaneous item generation phase, participants were asked about their attitudes, hopes and concerns prior to PI surgery, as well as changes in partner post-surgery. Participants were then asked whether they identified domains raised by the expert panel that were not mentioned during the spontaneous phase. Additional open-ended questions were asked about experiences before and after PI surgery. Interviews were transcribed verbatim for subsequent qualitative analysis by 2 trained members of the study team. Results 12 women have been interviewed. Mean partner age = 60 years, relationship duration = 20 years. Interviews were held <12 months post-PI for 17% of partners, 12-24 months for 25%, >24 months for 58%. Partner communication and involvement in decision to get the implant were uniquely raised as pre-surgical concerns, whereas PI attributes were uniquely mentioned as post-surgical concerns. How the PI has impacted the man’s self-esteem, whether impacts to self-esteem have affected the partner, and overall satisfaction with sex were most common concepts raised across pre- and post-surgery (See Table). Conclusions Using rigorous qualitative methodology, we have identified concepts that are unique to pre-surgery, post-surgery, and common across the surgical experience among partners of men who have undergone penile implant surgery. These data will facilitate development of a tool to assess female partner attitudes, beliefs and satisfaction prior to and after PI surgery. Disclosure No
Determination of Adult Critical Care Physician Core Knowledge and Skills: Results of a Multidisciplinary, Modified Delphi Process
Tisherman, Samuel A. , Spevetz, Antoinette, Farmer, Joseph C. , Michener, Ed, Sreedharan, Roshni , Strickler, Samantha , Cuschieri, Joseph , Ellender, Timothy J., Kaups, Krista L. , Keegan, Mark T. , Lee, May M. , Malaiyandi, Deepa , Michetti, Christopher P. , Mohr, Nicholas M. , Moitra, Vivek K. , O’Neil, Kevin , Palmieri, Tina L. , Park, Pauline K., Raksin, P B , Shapshak, Angela Hays , Siddiqui, Shahla , Stein, Deborah M. , Timmons, Shelly D. , Vespa, Paul , Wessman, Brian T. , Wittwer, Erica D. , Medicine, on behalf of the Adult Critical Care Physician Core Knowledge and Skills Task Force of the Society of Critical Care, Farmer, J Christopher, Mohr, Nicholas M , Kashyap, Rahul , Leichtle, Stefan W. , Chang, Cherylee W. J. , Yataco, Angel Coz , Dudzinski, David M. , Emlet, Lillian L. , Fahy, Brenda G. , Geller, Bram J. , Hennessey, Erin , Park, Pauline K. , Pathak, Abhijit S. , Medicine, on behalf of the Adult Critical Care Physician Core Knowledge and Skills Task Force of the Society of Critical Care, Siddiqui, Shahla

Critical Care Medicine | December 9, 2025 | Volume: 54 | Issue: 2 | Pages: 224-233

10.1097/ccm.0000000000006978 | PMID 41363909 Get It

Objectives: In the United States, training for physicians who manage critically ill adult patients (intensivists) evolved through parallel subspecialty critical care medicine (CCM) pathways with significant commonality. The Society of Critical Care Medicine Adult Critical Care Physician Core Knowledge and Skills Task Force aimed to delineate the common core knowledge and skills required of all intensivists. Design: A master list of content areas and procedural skills was compiled from all CCM subspecialty program requirements and blueprints of the certification examinations. Using a modified Delphi approach, participants were asked to categorize the knowledge items as “advanced knowledge is essential,” “general, but not advanced, knowledge is essential,” or “knowledge is not essential.” Procedures were categorized as “intensivist performs routinely,” “intensivist only performs in an emergency,” or “intensivist knows” about the procedure. Setting: Representatives from CCM stakeholder organizations, including accreditation and certification organizations, critical care societies, and program directors’ societies, were invited to participate. SUBJECTS: Members of the Adult Critical Care Physician Core Knowledge and Skills Task Force of the Society of Critical Care Medicine. Interventions: For the first two rounds of the modified Delphi process, Research Electronic Data Capture was used. For the third and fourth rounds, the process was completed through online meetings with Zoom (Zoom Video Corporations, San Jose, CA) utilizing Zoom’s polling feature. Measurements and Main Results: A total of 541 items were determined to be essential, with 145 requiring advanced knowledge and 323 requiring general knowledge. For 73 items, consensus regarding advanced vs. general could not be achieved, but they remained essential. Only eight items were felt to be nonessential. Of the 16 procedures, most were categorized as “intensivist performs.” Conclusions: The large number of items included in the list of essential knowledge and skills demonstrates the complexity of modern CCM. Utilization of a common framework across the subspecialties of CCM could lead to greater harmonization among the fellowship program requirements and certification examinations.
Accurate and Scalable Classification of Colonoscopy Neoplasia Using Machine Learning and Natural Language Processing
Broderick, Brendan T., Greenwood, Jason D. , Burger, Kelli N. , Garg, Sushil Kumar , Gurudu, Suryakanth, Ebner, Derek W. , Broderick, Brendan, Greenwood, Jason, Mahoney, Douglas, Burger, Kelli, Gurudu, Suryakanth R, Ebner, Derek , Kisiel, John, Mahoney, Douglas W. , Wallace, Michael B. , Kisiel, John B.

Clinical and Translational Gastroenterology | December 9, 2025 | Volume: 17 | Issue: 2 | Pages: e00959

10.14309/ctg.0000000000000959 | PMID 41363713 Get It

INTRODUCTION: Colorectal cancer remains a leading cause of cancer associated death in the United States and colonoscopy the primary screening strategy for prevention. Rates of adenomatous and serrated neoplasia detection are inversely associated with postcolonoscopy colorectal cancer. This crucial quality metric depends on accurate ascertainment of colorectal neoplasia findings from both endoscopy and histopathology records. We aimed to assess the feasibility of a random forest machine learning model to rapidly and accurately categorize colorectal neoplasia from electronic health record data. METHODS: A retrospective cohort study compared neoplasia detection rates among individuals undergoing colonoscopy at a large academic institution to develop a rule-based algorithm to categorize colorectal neoplasia from endoscopy reports and pathology systematized nomenclature of medicine – clinical terms. This cohort provided a large training set to develop a natural language processing system using a random forest approach to automatically classify unstructured pathology findings into adenoma, serrated, or advanced neoplasms. This system was manually validated through an independent holdout set. RESULTS: The training set comprised 35,953 unstructured pathology reports with matched systematized nomenclature of medicine – clinical terms from 95,188 unstructured colonoscopy reports. The final model was assessed on an independent holdout set of 337 manually annotated procedures obtaining an area under the receiver operating characteristic curve of 0.997 (confidence interval [CI] 0.994–1), 0.99 (CI 0.98–1), and 0.99 (CI 0.98–0.99) for prediction of adenoma, serrated, and advanced lesions, respectively. DISCUSSION: The random forest-based hybrid natural language processing system for classification of colonoscopy results was both accurate and explainable. NLP combined with effective machine learning algorithms can provide a scalable strategy for colonoscopy quality monitoring.
Diagnostic Performance and Interpreter Experience of 1-Hour Versus 3-Hour 99m Tc-HMDP Cardiac Amyloid Radionuclide Imaging: A Prospective, Blinded Comparison
Tersalvi, Gregorio , Carey, Patricia , Garmany, Armin , Scott, Christopher G. , Maldonado, Francisco J., Krüger, Leandi , Hruska, Carrie B. , Johnson, Geoffrey B. , Jouni, Hayan, Rodriguez‐Porcel, Martin , Askew, J. Wells , Bois, John P. , Young, Kathleen A. , Anavekar, Nandan S., Grogan, Martha , Homb, Andrew, Zhang, Jun , Kruger, Livia F , Hruska, Carrie B , Johnson, Geoffrey B , Rodriguez-Porcel, Martin G., Askew, J Wells , Young, Kathleen , Grogan, Martha , Dispenzieri, Angela , Chareonthaitawee, Panithaya , Homb, Andrew C, AbouEzzeddine, Omar F , Scott, Christopher , Tersalvi, Gregorio , Carey, Patricia , Zhang, Jun , Maldonado, Francisco J., Dispenzieri, Angela , Chareonthaitawee, Panithaya , AbouEzzeddine, Omar F.

Circulation: Cardiovascular Imaging | December 8, 2025 | Volume: 19 | Issue: 1 | Pages: No page available

10.1161/circimaging.125.018745 | PMID 41355666 Get It

BACKGROUND: Guidelines recommend 3-hour cardiac amyloid radionuclide imaging (CARI) for transthyretin amyloid cardiomyopathy. Citing rapid blood clearance of 99m Tc-hydroxymethylene-diphosphonate (HMDP) and efficient laboratory throughput, 1-hour imaging is increasingly practiced despite limited supporting evidence. We sought to compare diagnostic performance and interpreter experience of 1-hour versus 3-hour HMDP-CARI. METHODS: Consecutive patients with suspected transthyretin amyloid cardiomyopathy (n=114) underwent both 1-hour and 3-hour HMDP single photon emission computed tomography (CT)/CT. Two cardiologist-radiologist reader teams, blinded to imaging timepoint (1 versus 3 hours), assessed overall interpretation, single photon emission CT–based Perugini grade, interpretation difficulty, interpreter confidence, and need for CT-fused images for anatomic localization. Discordant, equivocal, and difficult cases were arbitrated by a third tie-breaking team. The myocardial-to-blood-pool radiotracer uptake ratio (3-dimensional Score) was measured as a surrogate of contrast resolution. RESULTS: Interinterpreter agreement was high at both time points (κ≥0.81), with more cases requiring arbitration at 3 hours versus 1 hour (22% versus 13%; P =0.049). Overall interpretation and Perugini grades were concordant between time points in 111/114 (97%) and 106/114 (93%) patients, respectively. Three patients (3%) were negative at 1 hour but equivocal at 3 hours, all of which were clinically ruled out for transthyretin amyloid cardiomyopathy. Interpreter confidence was comparable at both timepoints (97% versus 95%; P =0.317). Compared with 3-hour imaging, contrast resolution was inferior (lower 3-dimensional score, P <0.001) and CT fusion was more frequently needed (57% versus 31%, P <0.001) at 1-hour imaging. CONCLUSIONS: In a prospective, blinded comparison of 1-hour versus 3-hour HMDP-CARI, diagnostic performance and interpreter experience were similar, with readers requesting CT fusion more frequently at 1 hour to optimize myocardial-to-blood pool discrimination.
Transplant vs. Resection for Non-HCC Malignancies of the Liver
Thiyagarajan, Sibi Krishna , Jacover, Arielle , Verastegui, Alfredo , Poruk, Katherine E. , Verastegui, Alfredo , Stauffer, John

Livers | December 5, 2025 | Volume: 5 | Issue: 4 | Pages: 64

10.3390/livers5040064 Get It

Background: Surgical resection (SR) and liver transplantation (LT) are the main curative options for non-hepatocellular carcinoma (non-HCC) liver malignancies, including colorectal liver metastases (CRLMs), intrahepatic cholangiocarcinoma (iCCA), hilar cholangiocarcinoma (hCCA), and neuroendocrine tumor liver metastases (NETLMs). Resection aims for negative margins and adequate hepatic reserve, while LT offers treatment for unresectable disease but is limited by donor scarcity, immunosuppression, and ethical constraints. Methods: A targeted literature search (2005–2025) was conducted using PubMed and Google Scholar with predefined MeSH terms combining “liver resection,” “hepatectomy,” and “liver transplantation” across non-HCC malignancies. Relevant studies, reviews, and guidelines were included. Results: For CRLMs, SR remains standard with 5-year overall survival (OS) up to 58%, while LT offers 60–83% in highly selected unresectable cases. In iCCA, resection achieves median survival around 40 months, and LT yields OS up to 69% in very early or neoadjuvant-controlled disease. For hCCA, the Mayo protocol combining neoadjuvant therapy with LT provides 5-year OS of 65–80%. In NETLMs, LT achieves 63–97% OS under strict criteria. Conclusions: SR remains first-line for resectable non-HCC malignancies, while LT provides superior outcomes in unresectable yet biologically favorable disease, emphasizing careful selection and organ allocation.
Automated Insulin Delivery Is Beneficial in Adults With Insulin-Treated Type 2 Diabetes With and Without GAD65 Antibodies
Beck, Roy W. , Hirsch, Irl B., Raghinaru, Dan, Lum, John W. , Pinsker, Jordan E. , Kudva, Yogish C. , Group*, 2IQP Study, Desjardins, Donna, Kurek, Corey, Kaur, Ravinder Jeet , Livingood, Daine, Rizvi, Shafaq , Graham, Timothy E., Terry, Adrienne, Luker, Ryan, Mellenthin, Melanie, Rezac, Stephanie, Liljenquist, David R., Rogers, Justin, Williams, Jonathan, Christensen, Rochelle, Lee, In‐Kyoung, Malone, Joann, Spanakis, Elias K. , Singh, Lakshmi G., Churchill, Jade, Comen, Kathleen, Scott, William H., Davis, Georgia M. , Arroyo, Lizda Guerrero, Oladejo, Omolade , Usman, Sabeena, Ahmann, Andrew , Schmid, Caleb, Dean, Ariel, Branigan, Deborah , Caswell, Brittany, Heyerman, Tess, Tessman, Brian, Vanderheide, Jnh, Dennis, Brittany , Hendricks, Lisa, Reyes-Rodriguez, Clemente, Wolf, Valerie, Coyne, Kasey, Kravarusic, Jelena, Fronczyk, Evelyn, Herrmann, Stefanie, Penn, Samsam C., Blevins, Thomas , Casaubon, Luis, Espinosa, Valerie, Pandit, Keta, Perez, Jennifer, Stewart, Ana, Assir, Courtney, Fields, Cory, Kruger, Davida , Estrada, Kathleen, Jones, J. Kimberly, Mukhashen, Shereen, Corker, Natalie, Hunter, Heather, Layton, Paula, Brown, Sue A. , Afreen, Samina , Dhillon, Jasmeen, Emory, Emma, Fulkerson, David, Fuller, Morgan, Holmes, Viola, Kollar, Laura, Toole, Elyse, Levister, Camilla, O’Malley, Grenye , Ipek, Aslihan, Alabi, Denise, Ellis, Emily, Hassan, Shaziah, Ogyaadu, Selassie, Tamarez, Denisa, Weinstock, Ruth S. , Stone, Sheri , Bzdick, Suzan, Agostini, Lynn, Bulger, Jane , Wolpert, Howard , Atakov-Castillo, Astrid , Sullivan, Asya, Aia, Corinne, Brouillard, Elizabeth, Driscoll, Marsha, Lapier, Heather, Payra, Sherryl, Vancer, Louise, Averkiou, Xenia, Baran, Jesica, Holod, Rosanna, Litvicov, Patrisia, Mandava, Patali, Swinton, Sydney, Khakpour, Dori , Broyles, Frances E. , Marks, Sheryl, Mitchell, Tina, Hairston, Babette, Costello, Reilly, Curtis, Stella, Kamimoto, Jorge Jo, Peleckis, Amy J. , Sultan, Rahaf , Dalton-Bakes, Cornelia, Bourne, Patricia, Haidar, Ahmad, Pasqua, Melissa, Tardio, Vanessa , Moore, Adelyn, Kemp, Gabrielle, Raskin, Philip, Jordan, L.F., Shao, Baomei, DoNguyen, Trang, Meeks, Tram, Phan, Michael , Lesniak, Amanda, Becerra, Mario, Bellini, Natalie J. , Denallo, Erica, Lewis, Claudia , Tribout, Jerry, Tribout, Megan, DiFrancesco, Kathryn, Phillips, Kylie, Raghinaru, Dan, Campos, Tiffany, Morrell, Beth, Oduah, Vanessa, Cardenas-Villamil, Gabriela, Morales, Amanda, Murphy, Carlos, Strayer, Heidi, Spanbauer, Charles , Kollman, Craig, Sasson-Katchalski, Ravid, Piquette, Nicole, Wheatcroft, Alex, WHITE, KIRSTIN N., Carmelo, KC, Janicek, Robert, Gabrielson, Deanna, Mercado, Kevin, Beck, Roy W , Group*, 2IQP Study, Smith, Joshua W. , Christensen, Rochelle, Malone, Joann, Pasquel, Francisco J. , Tajrishi, Farbod Zahedi , Arroyo, Lizda Guerrero, Dean, Ariel, Howard, Matthew, Vander-Heide, Jesse, Ahn, David , Aleppo, Grazia , Fields, Cory, Layton, Paula, Oliveri, Mary Clancy , Levy, Carol J. , Agostini, Lynn, Steenkamp, Devin W , Spaic, Tamara , Liu, Selina , Marks, Sheryl, Mitchell, Tina, Costello, Reilly, Curtis, Stella, Rickels, Michael R. , Bourne, Patricia, Tsoukas, Michael A. , Pasqua, Melissa-Rosina , Moore, Adelyn, Kemp, Gabrielle, Meeks, Tram, Phan, Michael, Hatipoğlu, Betül , Lesniak, Amanda, Howard, Quiana , DiFrancesco, Kathryn, Raghinaru, Dan, Morrell, Beth, Morales, Amanda, Kanapka, Lauren , Le, Van

Diabetes Care | December 5, 2025 | Volume: 49 | Issue: 2 | Pages: e18-e20

10.2337/dc25-2059 | PMID 41348329 Get It

Can a Generative Artificial Intelligence Model Be Used to Create Mass Casualty Incident Simulation Scenarios? A Feasibility Study
Navarro, Sergio M. , Atkinson, Angie G., Donagay, Ege, Jabaay, Maxwell J, Lund, Sarah , Park, Myung S., Loomis, Erica, Zietlow, John , Vu, T. N. Diem , Rivera, Mariela , Stephens, Daniel , Jabaay, Maxwell, Loomis, Erica A, Zietlow, John M, Diem Vu, T N , Navarro, Sergio Michael , Atkinson, Angie G., Stephens, Daniel

Healthcare | December 5, 2025 | Volume: 13 | Issue: 24 | Pages: 3184

10.3390/healthcare13243184 | PMID 41464253 Get It

Introduction: Mass casualty incident (MCI) simulation scenarios are developed based on detailed review and planning by multidisciplinary trauma teams. This study aimed to assess the feasibility of using generative artificial intelligence (AI) in developing mass casualty trauma simulation scenarios. The study evaluated a range of mass casualty trauma simulation scenarios generated from a public generative artificial intelligence platform based on publicly available data with a validated objective simulation scoring tool. Methods: Using a large language model (LLM) platform (ChatGPT4, OpenAI, San Francisco, CA, USA), 10 complex MCI trauma simulation scenarios were generated based on publicly available US reported trauma data. Each scenario was evaluated by two Advanced Trauma Life Support (ATLS) certified raters based on the Simulation Scenario Evaluation Tool (SSET), a validated scoring tool out of 100 points. The tool scoring is based on learning objectives, tasks for performance, clinical progression, debriefing criteria, and resources. Two publicly available mass casualty trauma scenarios were similarly evaluated as controls. Revision and recommended feedback was provided for the scenarios, with review time recorded. Post-revision scenarios were evaluated. Interrater reliability was calculated based on Intraclass Correlation Coefficients (2, k) (ICCs). For the scenarios, scores and review times were reported as medians with interquartile range (IQR) as 25th and 75th percentiles. Results: Ten mass casualty trauma simulation scenarios were generated by an LLM, producing a total of 62 simulated patients. The initial LLM-generated scenarios demonstrated a median SSET score of 78.5 (IQR 74–82), substantially lower than the median score of 94 (IQR 93–95) observed in publicly available scenarios. The interrater reliability ICC for the LLM-generated scenarios was 0.965 and 1.00 for publicly available scenarios. Following secondary human revision and iterative refinement, the LLM-generated scenarios improved, achieving a median SSET score of 94 (IQR 93–96) with an interrater reliability ICC of 0.7425. Conclusions: The feasibility study suggests that a structured, collaborative workflow combining LLM-based generation with expert human review may enable a new approach to mass casualty trauma simulation scenario creation. LLMs hold promise as a scalable tool for the development of MCI training materials. However, consistent human oversight, quality assurance processes, and governance frameworks remain essential to ensure clinical accuracy, safety, and educational value.
Bone marrow adipocytes (BMA) as a novel biomarker of molecular response in patients with essential thrombocythemia (ET) and polycythemia vera (PV) treated with pegylated interferon alfa-2A
Johnson, Justin M. , Metzger, Megan , Barbui, Tiziano , Yacoub, Abdulraheem , Yu, Ashley , Kremyanskaya, Marina , Salama, Mohamed E. , Mascarenhas, John , Kosiorek, Heidi , Prchal, Josef T. , Rambaldi, Alessandro , Mesa, Ruben A. , Dueck, Amylou C. , Hoffman, Ronald

Blood | December 5, 2025 | Volume: 146 | Issue: Supplement 1 | Pages: 5590-5590

10.1182/blood-2025-5590 Get It

Abstract Background: The functional importance of bone marrow adipocytes (BMA) is frequently overlooked even though they are critical components of the BM (bone marrow) microenvironment. BMA have been proposed to play a supportive role within the hematopoietic niche and to directly sustain hematopoietic stem cell (HSC) survival as well as to preferentially support leukemia cell survival and proliferation (Sabbah Cell Commun Signal 2023). Although significant ex-vivo data implicates direct and indirect crosstalk between BMA and neoplastic HSCs (Venti Front Endocrinol 2022), the possible role of BMA in myeloproliferative neoplasms and their dynamics following therapy have yet to be characterized. Adiponectin, an anti- inflammatory adipokine that maintains metabolic homeostasis through regulation of insulin sensitivity, lipid metabolism and pro-inflammatory signaling is low in MPN patients and increases with IFN-α therapy (Avcu Int J Hematol. 2006). IFN-α has also been implicated in inhibiting adipogenesis via JAK-STAT1 signaling (Lee Biochim Biophys Act. 2016). A single institutional study of IFN-α in patients with essential thrombocythemia (ET) and polycythemia vera (PV) confirmed the potential for BM histopathologic responses and a correlation with molecular responses (Masarova Exp Hematol Oncol 2017). The aim of this analysis was to characterize the change in BM cellularity and fat composition with pegylated IFN α-2a (Pegasys; PEG) and the relationship with both hematologic and molecular response from tissue collected in prospective, global clinical trials of PEG in patients with ET/PV. Methods: A total of 24 subjects from the phase 2 MPN-RC 111 (Yacoub Blood 2019) salvage PEG study and 16 subjects from the MPN-RC 112 (Mascarenhas Blood 2022) phase 3 study comparing PEG to HU with available clinical, BM H&E slides, laboratory and molecular data were included in this retrospective analysis of prospective clinical trial data. We assigned a semi-quantitative score for changes in cellularity, fat distribution, and megakaryocyte (MK) histo-topography for changes from baseline, at 12, 24 and 36 months when available. Changes in BMA content and para-trabecular distribution were assessed on whole slide digital images with machine learning models. BMA content was quantified with a QuPath pixel classifier that distinguished adipocytes from other marrow components (Bankhead Scientific Reports 2017). Para-trabecular adipocyte distribution was assessed by leveraging UNI2-h, a self-supervised Vision Transformer (ViT-H/14) model and successor to UNI (Mahmood Nature 2024). UNI2-h was pre-trained on 200 million image tiles from over 300,000 H&E and IHC slides. In this study, UNI2-h was adapted to distinguish between high and low para-trabecular adiposity using image tiles centered on trabeculae. Trabeculae with a surrounding layer of adipocytes were labeled as ‘high’ adiposity, while ‘low’ para-trabecular fat distribution was defined by the direct contact of cellular marrow with trabeculae, lacking surrounding adipocytes. Results: A total of 40 PEG-treated ET (n=18) and PV (n=22) patients were included in this analysis with a median age of 64 years (26-85), 77% JAK2V617F+, 23% CALRmut+, and 40% treatment-naïve. The median JAK2V617F variant allele fraction (VAF) was 26% (range 3-96%). A complete hematologic response (CHR) was obtained with PEG in 58%, 61% attained &gt;20% reduction in driver VAF and 48% attained a &gt;50% reduction in VAF (MR) within 24 months of baseline. We observed an increase in BMA content and notable increase in para-trabecular distribution (confirmed by morphology and ML, independently) in 93% and 53% of PEG treated patients attaining a MR versus only 31% and 6% who did not attain MR, respectively (P Value=0.0004). There was more notable improvement towards normalization of MK histo-topography and orderly erythropoiesis in MR (86.6%) than in non-MR (31.2%) (P value=0.001). Increase in BMA content, BMA para-trabecular distribution, or improvement in MK histo-topography were not associated with achievement of CHR or changes in CALR VAF in this small cohort. Cytokine correlation with BMA dynamics is currently ongoing and will be reported at the meeting. Conclusion: Treatment of MPN patients with IFN-α resulted in reproducible changes in BM cellularity including MK histo-topography, erythropoiesis, BMA number and distribution. Changes in BMA were closely associated with reduction in JAK2V617F VAF following PEG treatment.
Nivolumab with doxorubicin, vinblastine, and dacarbazine (NAVD) in older adults with classic Hodgkin lymphoma: Do S1826 results hold up in the real world?
Torka, Pallawi , Bock, Allison M. , Vaughn, John, Thiruvengadam, Swetha, Sekaran, Kanithra , Lee, Calvin , Smilnak, Gordon , Patel, Vrutti , Baek, Grace , Mynam, Ritwick , Sano, Dahlia , Gerber, Drew, Palmeri, Marisa, Mrad, Rudy, Sharp, John , Geethakumari, Praveen Ramakrishnan , Karimi, Yasmin , Feldman, Tatyana , Svoboda, Jakub , Shanmugasundaram, Krithika , Herrera, Alex F. , Karimi, Yasmin H , Назаренко, Елена Борисовна , Xu, Yizhe , Vaughn, John, Thiruvengadam, Swetha, Major, Ajay , Reef, Daniel K. , Luttwak, Efrat , Shah, Harsh , Ip, Andrew , Falade, Ayo , Iqbal, Madiha , Voorhees, Timothy , Rhodes, Joanna , Durani, Urshila , Cherng, Hua‐Jay J. , Pophali, Priyanka A. , Di, Mengyang , Niu, Alex , Grover, Natalie S. , Karmali, Reem , Diefenbach, Catherine , Epperla, Narendranath

Blood | December 5, 2025 | Volume: 146 | Issue: Supplement 1 | Pages: 3622-3622

10.1182/blood-2025-3622 Get It

Abstract Introduction: Older adults (OAs) with classic Hodgkin lymphoma (cHL) have inferior survival compared with younger patients (pts). NAVD has been widely adopted in clinical practice for frontline (1L) treatment of OAs with advanced stage cHL based on the subset analysis of S1826 study (Rutherford et al, JCO 2025) showing a 1-year progression-free survival (PFS) of 93% and 1-year overall survival (OS) of 95% after NAVD (n = 50) which remained durable on longer-term follow up. Another phase 2 study (Torka et al, JCO 2025) showed that NAVD is a highly effective and well-tolerated 1L regimen in OAs with cHL (n=40) across a wide range of geriatric impairments. Adverse events (AEs) and efficacy have not been reported in OAs treated with NAVD outside of a clinical trial. Hence, we sought to evaluate safety profile and efficacy outcomes of OAs with cHL treated with 1L NAVD in a real-world setting (RWS). Methods This is a multicenter retrospective cohort study of adults (≥18 years) with cHL treated with 1L NAVD between 2023 and 2025 at 20 US academic sites. Baseline characteristics and outcomes of pts ≥60 years were evaluated as a pre-planned subset analysis. The safety evaluable cohort received at least 1 cycle of NAVD and included pts who had not yet completed treatment. The efficacy evaluable cohort had completed 6 cycles of treatment including end of treatment (EOT) PET-CT and included pts who intended to complete treatment but died or discontinued due to progressive disease or AEs. The primary endpoint was EOT overall response rate (ORR). Secondary endpoints included EOT complete response rate (CRR), PFS and OS. PFS and OS were analyzed using the Kaplan Meier method. Results Among 311 pts, 81 were OAs (26%). Median age of the OA cohort was 70 (range 60-88) yrs, 65% male, 84% Caucasian, 71% nodular sclerosis subtype, 58% stage 4 disease, 59% B symptoms, 14% bulky disease (&gt;7.5 cm), 69% extranodal sites, 41% EBV positive, 54% hypoalbuminemia, 49% IPS ≥ 4 and10% had an autoimmune disease. G-CSF was given in 81% pts. All 81 pts were evaluable for safety; 74% experienced a grade 3+ (≥G3) AE, 54% had ≥G3 hematological AE, 48% had ≥G3 neutropenia, 17% had febrile neutropenia. Infection rate was 28% with 10% ≥G3, neuropathy rate was 23% with 4% ≥G3. One infusion reaction was noted. Treatment related hospitalizations rate was 23% with median duration of 7 (range 1-16) days. There were 24 immune related AEs (IrAE) (30%) of which 5 were ≥G3. Most common IrAE was hypothyroidism (n=5), followed by inflammatory arthritis (n=4), pneumonitis (n=2, ≥G3, n=1), hepatitis (n=2, both ≥G3), adrenal insufficiency (n=2, ≥G3, n=1), colitis (n=2), and rash (n=2). One patient each had autoimmune neutropenia, sarcoidosis of lung/skin and myocarditis (≥G3). Overall, 15% pts required steroids with resolution of IrAEs in 56% cases, 30% (n=7) pts required continued therapy (levothyroxine in 4 pts, steroids in 3 pts, medical tx for heart failure in 1 pt). Treatment was interrupted in 22%, reduced in 22%, and discontinued in 23% pts. Nivolumab was discontinued in 14% pts. Among all pts (n=81), 81% had an interim PET-CT after 2-4 cycles. The ORR and CR rate at interim PET-CT were 100% and 81%, respectively. In the efficacy evaluable pts (n=52; 24 still on therapy), the EOT ORR and CRR were 93.2% and 84% in OAs compared to 96.8% and 91.7% in pts &lt;60yrs, respectively. At a median follow up of 10.2 mo (range 0.27-28.52), the 1-yr PFS was 90.6% (95% CI: 82.7%-99.3%) in OAs and 95.5% (95% CI: 91.6%- 99.6%) in pts &lt;60 yrs (p=0.044). 1-yr OS was 97.5% (95% CI: 94.1-100%) and not evaluable in pts &lt;60yrs (p=0.017). None of the baseline features were predictive of response, additional analysis to understand impact on AEs and survival is ongoing. Among the 5 pts with progression/relapse, 4 were primary refractory. 4 pts received 2nd line (2L) therapy.79 pts are alive at data cut off, 2 deaths occurred- 1 infection-related and other unknown; both after the 1st cycle. Conclusions In this largest RWS cohort of OAs treated with NAVD we showed comparable response rates, AEs and 1-year survival outcomes to those in the pivotal S1826 trial. Notably, rates of ≥G3 AEs including infections, neuropathy and IrAEs remained low and manageable. Although survival significantly improved with NAVD compared to historical data, outcomes of OAs remained inferior compared to pts &lt;60 yrs. Our data reinforces the use of NAVD as the preferred 1L option for OAs with advanced stage cHL.