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Single‐Operator Stress Ultrasound Evaluation of Ulnohumeral Joint Instability Related to Medial Ulnar Collateral Ligament Injury
Kopecky, Benjamin F. , Boettcher, Brennan J. , Sellon, Jacob L. , Camp, Christopher L. , Sellon, Jacob L , Kopecky, Benjamin

Journal of Ultrasound in Medicine | July 25, 2026 | Volume: No volume available | Issue: No issue available | Pages: No page available

10.1002/jum.70391 | PMID 42501408 Get It

This article introduces a novel, single‐operator stress ultrasound technique for evaluating medial ulnar collateral ligament (MUCL) integrity by assessing medial ulnohumeral joint (MUHJ) widening under valgus stress. Unlike prior methods requiring dual operators, specialized equipment, or the use of hand/wrist weights, this approach was designed for clinical efficiency, reproducibility, and patient comfort. By positioning the patient comfortably in a side‐lying position with the elbow flexed to 50°, MUHJ width is measured at baseline (maximally apposed) and manually stressed positions, in a manner that may reduce muscular compensation, avoid viscoelastic creep, and facilitate consistency. While additional research is needed to evaluate clinical feasibility, assess reliability, and compare our technique with previously published methods of dynamic MUCL assessment, the aim of this manuscript is to describe our technique and provide a rationale for its potential utility in musculoskeletal ultrasound practice and research.
Advancing Prostate Cancer Survivorship Through Transatlantic Consortium Science: The iCCaRE Initiative
Odedina, Folakemi T. , Dronca, Roxana , Ashing, Kimlin , Kaninjing, Ernest , Rotimi, Solomon O. , Ngufor, Che , Merriweather, Arnold , Gordon, Vinessa , Asto-Flores, Emelina , Adeniji, Kayode, Agboola, Emmanuel, Aliche, Uju, Aliyu, Usman M., Ashing, Kimlin Tam, Asiedu, Gladys, Badejo, Paul, Johnson, Kim Barbel, Beckford, Patrick , Blocker, Renaldo, Bolajoko, Opeyemi, Bonner, Timethia J, Breland, Ivey, Caballero, Amanda , Carter, Rickey, Cattnell, Alex, COBRAN, Ewan, Colon-Otero, Gerardo, Copland, John A., Phd, Getachew Dagne, Campos, Opeyemi C. De, Doty, Melissa, Dronca, Roxana, Erefah, Ebenezer, Falzon, Kaila, Francis, Damian, Fudge, Michelle, Fullwood, Dottington , Gainer, Jeffery, Glaser-Boivin, Dee, Hill, Antony, Hinsom, Rakenya, Iweala, Emeka J., Kaninjing, Ernie, Kase, Adam, Knutsen, Keith, Lee, Daniel, Leyva, Sandra Casanova, Lindeman, Carolyn R., Mahin, Collisa, Maniaci, Michael, Hew, Trevanne Matthews, Hew, Trevanne R. Matthews, Melton, Jada K., Merriweather, Arnold, Mitchell, Luisa, Moore, Cassandra, Ngufor, Che, Nolan, Lucia, Odedina, Abimbola, Odedina, Folakemi, Oladoyinbo, Catherine, Olasehinde, Esther, Onyia, Abimbola F., Popoola, Ademoola, Rotimi, Solomon O., Scales, Tracie, Sledge, Hanna, Thompson-Reeves, Jade, Toye, Oluwaseyi, Duarte, Claudia Valles, Voorhis, Kaitlin Van, Waldon, Charles F., Walsh-Childers, Kim , Williams, Christopher, Willis, Floyd , Wimberly, Quincy , Yahaya, Ayinde, Yates, PhD Clayton, Yost, Kathleen, Young, Mary Ellen , Zou, Tingyu, Ashing, Kimlin Tam , Rotimi, Solomon , Odedina, Folakemi , Kaninjing, Ernest T , Ngufor, Che G , Aliche, Uju, Badejo, Paul, Blocker, Renaldo, Bolajoko, Opeyemi , Cattnell, Alex, Cobran, Ewan K. , Colon-Otero, Gerardo, Copland, John A., Francis, Damian, Fudge, Michelle , Gainer, Jeffery, Gokara, Mahesh , Hinsom, Rakenya, Iweala, Emeka J., Knutsen, Keith, Lee, Daniel, Lindeman, Carolyn R., McCall, John , Melton, Jada K., Mitchell, Luisa, Olasehinde, Esther, Popoola, Ademoola, Reynolds, Jordan , Scales, Tracie, Sledge, Hanna, Thompson-Reeves, Jade, Toye, Oluwaseyi, Duarte, Claudia Valles, Voorhis, Kaitlin Van, Waldon, Charles F., Williams, Christopher, Yost, Kathleen, Zou, Tingyu

Cancer Research Communications | July 24, 2026 | Volume: No volume available | Issue: No issue available | Pages: No page available

10.1158/2767-9764.crc-26-0165 | PMID 42497456 Get It

Abstract Black/African American populations, globally, bear the greatest prostate cancer (CaP) burden compared to other racial/ethnic groups. Addressing CaP disparities in Black men is complex, requiring a patient-centered, community-centric and comprehensive approach. This study integrates iCCaRE Consortium findings and broader literature to address unmet needs in survivorship care. The iCCaRE Consortium implemented five complementary pilot studies using mixed-methods designs, including feasibility trials, qualitative research, and observational analyses across the United States and sub-Saharan Africa. Descriptive statistics, subgroup analyses, and qualitative thematic analyses were performed across these studies. Collectively, projects addressed multilevel determinants including social, behavioral, and biological drivers of disparities. Project 1 implemented a Virtual Reality Assistant (ViRA) across clinical and community settings, with ongoing evaluation in pragmatic trials. Project 2 showed strong patient preference for home-based cancer care. Project 3 enrolled demonstrated trends toward improved health-related quality of life. Project 4 identified key themes influencing survivorship experiences. Project 5 identified biological mechanisms linking stress, immune modulation, and symptom burden. The iCCaRE pilot projects demonstrate the feasibility and early impact of a consortium-based, transdisciplinary approach to addressing CaP disparities in Black men. These findings highlight the importance of integrating patient-centered interventions, community engagement, and biological insights to inform scalable strategies aimed at improving survivorship outcomes and advancing health equity. The iCCaRE Consortium demonstrates that a transatlantic, patient-centered, and multidisciplinary approach integrating social, clinical, and biological factors can generate scalable strategies to improve survivorship outcomes and advance equity in CaP care for Black men.
First-pass aspiration versus stent retriever thrombectomy: machine learning study of treatment effect heterogeneity
Chen, Huanwen , Isidor, Julio , Schirmer, Clemens, Ernst, Marielle , Rai, Ansaar, Jabbour, Pascal , Abecassis, Isaac Josh , Grossberg, Jonathan A , Alawieh, Ali, Khanna, Omaditya, Starke, Robert M, Psychogios, Marios-Nikos, Siddiqui, Fazeel, Samaniego, E, Goyal, Nitin, Ezzeldin, Mohamad , Dye, Justin, Alcedo, Rodolfo, Cerejo, Russell , Luther, Evan, Romano, Daniele G, Tanweer, Omar, Mascitelli, Justin, Cuellar, Hugo H, Chalouhi, Nohra , Limaye, Kaustubh, Kellogg, Ryan, Brinjikji, Waleed, Chowdhry, Shakeel , Spiotta, Alejandro M , Kan, Peter , Jabbour, Pascal , Abecassis, Isaac Josh , Grossberg, Jonathan A , Navia, Pedro , Ezzeldin, Mohamad , Alaraj, Ali , Yoshimura, Shinichi , Fiorella, David , Fragata, Isabel , Mokin, Maxim , Matouk, Charles , Chowdhry, Shakeel A , Altschul, David J , Ogilvy, Christopher S , Levitt, Michael R , Grandhi, Ramesh , Spiotta, Alejandro M , Kan, Peter , Kim, Jae‐Joong , Rai, Ansaar , Jabbour, Pascal , Navía, Pedro , Starke, Robert M. , Psychogios, Marios‐Nikos , Goyal, Nitin , Dye, Justin , Alaraj, Ali , Yoshimura, Shinichi , Almallouhi, Eyad , Fiorella, David , Romano, Daniele Giuseppe , Tanweer, Omar , Fragata, Isabel , Mascitelli, Justin R , Limaye, Kaustubh , Matouk, Charles , Kellogg, Ryan Thomson , Brinjikji, Waleed , Altschul, David , Ogilvy, Christopher S. , Levitt, Michael R. , Grandhi, Ramesh

Journal of NeuroInterventional Surgery | July 24, 2026 | Volume: No volume available | Issue: No issue available | Pages: jnis-2026-025615

10.1136/jnis-2026-025615 | PMID 42498630 Get It

Background Randomized trials have shown equivocal outcomes between a direct aspiration as first-pass technique (ADAPT) and stent retriever (SR) stroke thrombectomy, yet whether specific patient subgroups benefit differentially from one technique over the other remains unknown. Methods In this retrospective multicenter cohort study, patients with large vessel occlusion were included, and those who underwent ADAPT versus SR first-pass thrombectomy (either as standalone or combined with aspiration) were compared. The primary outcome was a composite of first-pass effect (FPE, modified Thrombolysis In Cerebral Infarction (mTICI) 2c or better with one attempt) with no symptomatic intracranial hemorrhage (sICH). A causal forest model was used to estimate the conditional average treatment effect (CATE) for each patient, with larger CATEs indicating that ADAPT is expected to be more advantageous. Patients were stratified by CATEs, and outcomes were compared between treatment groups. Results Among 6700 included patients, ADAPT (n=3695, 55%) was associated with a higher rate of FPE with no sICH (39.9% vs 26.9%; adjusted OR (aOR) 2.07, 95% CI 1.77 to 2.41, P<0.001). The causal forest identified significant treatment effect heterogeneity (interaction P<0.001), where ADAPT was more advantageous in more recent years and among patients with M1 occlusions presenting in earlier time windows. Low-CATE patients showed no statistically significant difference between techniques (aOR 0.91, 95% CI 0.57 to 1.45, P=0.70), while medium- and high-CATE patients demonstrated progressively larger ADAPT advantages (aOR 2.06, 95% CI 1.67 to 2.55, and aOR 2.99, 95% CI 2.24 to 3.98, respectively, both P<0.001). Conclusions ADAPT may be superior to SR for a majority of patients, particularly in recent years, and among patients with M1 occlusions presenting in earlier time windows.
A Case of Five Primary Microcystic Adnexal Carcinomas in a Young Adult
Smith, Sarah E. B. , Pittelkow, Mark, Arpey, Christopher, Arpey, Christopher J.

Dermatologic Surgery | July 24, 2026 | Volume: No volume available | Issue: No issue available | Pages: No page available

10.1097/dss.0000000000005273 | PMID 42496492 Get It

Bridging Conservative Management With Injectable Orthobiologic Therapies: Proceedings of the International Consensus Meetings on Cartilage Repair of the Ankle
Tham, Alexander, Rubin, Jared, Butler, James J., Gauthier, Paloma , Kennedy, John G. , Adams, Samuel B., Andrews, Carol L., Batista, Jorge , Baur, Onno L., Bayer, Stephen, Becher, Christoph, Berlet, Gregory C. , Boakye, Lorraine AT, Buda, R, Calder, James D. F., Dahmen, Jari , D’Hooghe, Pieter, DiGiovanni, Christopher W., Ehlers, M. , Ferkel, Richard D. , Ferkel, Eric, Ferrao, Paulo N. F., Giza, Eric , Gianakos, Arianna L., Glazebrook, Mark, Gomaa, Mohamed, Görtz, Simon, Haleem, Amgad M. , Hamid, Kamran S. , Hangody, László, Haverkamp, Daniel, Hertel, Jay, Hintermann, Beat, Hogan, MaCalus V., Hunt, Kenneth J., Hurley, Eoghan T., Karlsson, Jon, Kearns, Stephen R. , Kerkhoffs, Gino M. M. J., Kim, Hak Jun , Kong, Siu Wah, Krebsbach, Sebastian, Labib, Sameh A. , Lambers, Kaj T. A. , Lee, Jin Woo, Lee, Keun Bae, Ling, Jeffrey S., Longo, Umile Giuseppe, Marangon, Alberto, McCollum, G, McCullough, Kirk, Mittwede, Peter N. , Murawski, Christopher D. , Nicolescu, Raluca, Niemeyer, Philipp, Nunley, James A., O'Malley, Martin, Ortiz, Cristian, Osei-Hwedieh, David O. , Paul, Jochen , Pearce, Christopher J., Pereira, Hélder , Phadke, Rohan , Prado, Marcelo P. , Raikin, Steven M., Reilingh, Mikel L., Robert, Guillaume , Lc, Schon, Simpson, Helene, Smyth, Niall A. , Sofka, Carolyn M., Spennacchio, Pietro, Stone, James W., Takao, M, Tanaka, Yasuhito, Thermann, Hajo, Thordarson, David B. , Rs, Tuan, Valderrabano, Victor, Bergen, Christian J. A. van, Dijk, Pim A. D van, Dijk, Niek van, Vannini, Francesca, Vaseenon, Tanawat , Volesky, Monika , Walls, Raymond C., Walther, Markus, Wiewiorski, Martin, Xu, Xiangyang, Yasui, Youichi , Yinghui, Hua, Yoshimura, Ichiro, Younger, Alastair , Zdanowicz, Urszala, Zhang, Zijun, Adams, Samuel B. , Clanton, Thomas O , Dahmen, Jari , Ehlers, Mallory , Hannon, Charles P , Labib, Sameh A , Popchak, Adam , Robert, Guillaume , Smyth, Niall A , Tham, Alexander , Rubin, J Peter , Butler, James J., Angthong, Chayanin , Becher, Christoph, Boakye, Lorraine A. T. , Buda, Roberto , Calder, James D. F. , Canata, Gian Luigi , Carreira, Dominic S. , Dahmen, Jari , d’Hooghe, Pieter P. R. N. , DiGiovanni, Christopher William , Dombrowski, Malcolm E. , Ferkel, Eric I. , Ferrao, Paulo N. F. , Gianakos, Arianna L. , Glazebrook, Mark Anthony , Gomaa, Mohamed, Hannon, Charles P. , Haverkamp, Daniël , Hintermann, Beat , Hogan, MaCalus Vinson , Hunt, Kenneth John , Hurley, Eoghan T. , Karlsson, Jon, Kerkhoffs, Gino M. M. J. , Krebsbach, Sebastian , Lee, Jin Woo , Longo, Umile Giuseppe , Mitchell, Adam W. , Nehrer, Stefan , Niemeyer, Philipp , Nunley, James A. , O’Malley, Martin , Pearce, Christopher Jon , Pereira, Hélder , Raikin, Steven M. , Rothrauff, Benjamin B. , Schon, Lew Charles , Spennacchio, Pietro , Sullivan, Martin, Tanaka, Yasuhito , Valderrábano, Víctor , Dijk, Pim A. D. van , Vannini, Francesca , Walther, Markus , Wiewiorski, Martin J., Xu, Xiangyang , Yoshimura, Ichiro , Zhang, Zijun

Foot & Ankle Specialist | July 24, 2026 | Volume: No volume available | Issue: No issue available | Pages: No page available

10.1177/19386400261456925 | PMID 42495946 Get It

Background The management of osteochondral lesions of the talus (OLT) is challenging, with 2 main options being conservative and surgical management. Orthobiologic therapies come to bridge the gap between these 2 options; however, inconsistencies in indication, composition, and heterogeneous evidence limit clinical decision-making. To address these challenges, 3 International Congress Meetings on Cartilage Repair of the Ankle were convened in Pittsburgh, USA (2017), Dublin, Ireland (2019), and New York, USA (2025) to establish agreement on the role of conservative management and injectable orthobiologic strategies in the treatment of OLT. Methods Seventy-five multidisciplinary experts from over 25 countries and 1 territory participated in a structured Delphi-based consensus process. Blinded surveys, structured questionnaires, and in-person discussions were used to develop and refine statements, supported by literature review and graded evidence (A1–E). Consensus strength was defined as consensus (51%-74%), strong consensus (75%-99%), or unanimous (100%) Results In total, 29 consensus statements were achieved across the 3 meetings. Strong agreement was reached regarding indications and expected outcomes of conservative management, including the role of immobilization and appropriate timing for surgical intervention. Orthobiologic injections, including platelet-rich plasma, concentrated bone marrow aspirate, and hyaluronic acid, were considered appropriate in select patients with persistent symptoms, although no superiority was demonstrated among formulations, preparation methods, or injection strategies. When used as adjuncts to surgical procedures, orthobiologics may improve radiological outcomes, with limited evidence for improvement in clinical outcomes. Technical considerations, including preferred harvest sites and a lack of standardized preparation protocols, were identified, along with key principles for patient counseling Conclusion These international consensus statements establish a standardized framework for the conservative management and use of injectable orthobiologic therapies in OLT. By clarifying indications, technical considerations, and current limitations, this work aims to improve consistency in clinical practice, guide treatment decision-making, and inform future research.
Pathology-Based Validation of Quantitative SPECT/CT in Patients With Suspected Transthyretin Amyloid Cardiomyopathy
Tersalvi, Gregorio , Bois, Melanie C. , Scott, Christopher G. , Carey, Patricia , Garmany, Armin , Davies, Daniel R. , HOFFMAN, Andrew C., Zhang, Jun , Hruska, Carrie B. , Jouni, Hayan, Rodriguez-Porcel, Martin G., Askew, J. Wells , Bois, John P. , Young, Kathleen A. , Anavekar, Nandan S., CHANG, IAN C., Grogan, Martha , Maleszewski, Joseph J. , Homb, Andrew, Redfield, Margaret M. , Dispenzieri, Angela , Maleszewski, Joseph J , Homb, Andrew C, Redfield, Margaret M , Chareonthaitawee, Panithaya , Johnson, Geoffrey B , AbouEzzeddine, Omar F , Hruska, Carrie B , Scott, Christopher , Tersalvi, Gregorio , Carey, Patricia , Rodriguez‐Porcel, Martin , Anavekar, Nandan S., Dispenzieri, Angela , Chareonthaitawee, Panithaya , Johnson, Geoffrey B. , AbouEzzeddine, Omar F.

Circulation: Cardiovascular Imaging | July 23, 2026 | Volume: 19 | Issue: 8 | Pages: No page available

10.1161/circimaging.126.019832 | PMID 42488949 Get It

BACKGROUND: Technetium-based cardiac amyloid radionuclide imaging enables noninvasive diagnosis of transthyretin amyloid cardiomyopathy (ATTR-CM), but conventional planar and visual semiquantitative approaches have important limitations. We developed the quantitative 3-dimensional Mayo 3D Score, defined as the ratio of mean left ventricular myocardial radiotracer uptake to right atrial blood-pool uptake using computed tomography (CT)-fused single-photon emission CT (SPECT) volumes of interest, and sought to validate its diagnostic performance against myocardial pathology. METHODS: Consecutive patients who underwent 99m Tc-pyrophosphate SPECT/CT at Mayo Clinic for suspected ATTR-CM between June 2017 and January 2025 with archived myocardial tissue were included. Baseline characteristics, including demographics, echocardiogram, biomarkers, visual semiquantitative, and Mayo 3D Score metrics, were collected. Myocardial specimens underwent histopathologic confirmation of amyloid, with amyloid subtype determination and further semiquantitative grading of amyloid burden and deposition patterns. RESULTS: Among 230 patients (median age, 72 years; 78% male), 107 (47%) had ATTR-CM, of whom 9 had hereditary ATTR-CM. The Mayo 3D Score showed excellent discrimination against pathology (area under the receiver operating characteristic curve, 0.92 [0.88–0.96]), exceeding planar Perugini (0.87 [0.83–0.92]; P =0.006), and heart-to-contralateral lung ratio (0.86 [0.81–0.91]; P =0.004) and comparable to SPECT Perugini (0.90 [0.86–0.94]; P =0.12). A cutoff ≥1.0 yielded 86.0% sensitivity, 92.7% specificity, 91.1% positive predictive value, and 88.4% negative predictive value. Among ATTR-positive cases, the Mayo 3D Score correlated strongly with semiquantitative amyloid burden (Spearman ρ=0.69), was higher in pericellular than nodular deposition patterns ( P <0.001), and was not associated with vascular involvement ( P =0.42). CONCLUSIONS: In patients with suspected ATTR-CM undergoing 99m Tc-pyrophosphate SPECT/CT, the Mayo 3D Score demonstrated superior diagnostic performance compared with planar metrics and comparable to SPECT Perugini, while correlating with myocardial ATTR burden and deposition patterns on pathology. These findings support its integration as a quantitative adjunct within clinical diagnostic ATTR-CM workflows.
Advances in Semantic Web
Holford, Matthew, Cheung, Kei‐Hoi, Zheng, Mingna, King, T. A. , Krauthammer, Michael O. , Chute, Christopher G.

No container title available | July 23, 2026 | Volume: No volume available | Issue: No issue available | Pages: No page available

10.4236/9781618962648 Get It

<p class="MsoNormal"> <span lang="EN-US">The Semantic Web has the ultimate goal of making a machine understand Internet data. To enable the encoding of semantics with the data, well-known technologies are used such as RDF (Resource Description Framework) and OWL (Web Ontology Language). These technologies formally represent the meaning involved in information. For example, ontology can describe concepts, relationships between things, and categories of things. These embedded semantics offer significant advantages such as reasoning over data and dealing with heterogeneous data sources.<o:p></o:p></span> </p>
Use of dermoscopy and its association with skin lesion evaluation confidence among PAs in the United States
Middleton, Hayden T. , Young, Peter A. , Kolhoff, Sean, O’Laughlin, Danielle , Swanson, David C. , Sartori-Valinotti, Julio C., Weatherly, Renee M., Boswell, Christopher L. , Tapia, Amanda L. , Sartori‐Valinotti, Julio C.

Journal of Dermatology for Physician Assistants | July 22, 2026 | Volume: 20 | Issue: 3 | Pages: 14-20

10.1097/jdpa.0000000000000108 Get It

Introduction: Limited research explores dermoscopy use among physician associates (PAs), outside of one prior study examining dermoscopy in PA student education. This study sought to investigate dermoscopy use among practicing PAs and its impact on their overall diagnostic confidence, including in darker skin tones, when differentiating between benign and malignant skin lesions. Methods: An anonymous survey was developed in 2023 with input from experts in dermoscopy and survey creation to assess PA confidence in skin lesion evaluation as well as PA dermoscopy knowledge and use, perceptions, barriers to use, and prior education. The dermoscopy survey was included as an optional module in the 2024 American Academy of Physician Associates (AAPA) Salary Survey. Results: Of 3,174 invited PAs, 995 (31.4%) responded. Most had never used dermoscopy in practice (81%) but knew or recognized the term (71%). A majority (53%) believed PAs should be trained in dermoscopy during PA school, and 26% reported no interest in future dermoscopy use. Dermatology PAs reported more frequent dermoscopy use and generally greater confidence in evaluating skin lesions, both overall and in darker skin tones, than PAs in other specialties. PAs in surgical (OR=0.2, 95% CI 0.1-0.6) and medical (OR=0.3, 95% CI 0.2-0.5) subspecialties were less likely to use dermoscopy at least annually compared with PAs in primary care. PAs in rural areas were more likely to feel confident in differentiating skin lesions than those in urban areas (OR 2.9, 95% CI 1.7-5.0). Conclusion: Dermoscopy use is associated with higher overall skin lesion assessment confidence. Wider adoption, especially outside dermatology, requires training, increased advocacy, and expanded education.
Molecular and Structural Basis of Pan-Resistance to BTK Degraders and Inhibitors
Sievers, Quinlan , Lu, Hao , Cool, Allison , Gajewski, Stefan , Kong, Tim , Noviski, Mark , Whelan, Sarah , Wang, Yuhan , Navarrete, Lizbeth Mendoza, Mi, Xiaoli , Mukerji, Ratul , Ye, Jordan , Rios, Mateo Sanchez Garcia de los, Bousquet, Hugo , Tan, Y. , Brathaban, Nivetha , Narasappa, Nell , Lu, Ya‐Wen , Elechko, Jennifer, Phelps, Christopher B., Sekeres, Samantha, Bravo, Eduardo , Alencar, Alvaro J. , Islam, Prioty , Mato, Anthony R. , Noviski, Mark A , Wang, Yuhan , Mendoza Navarrete, Lizbeth , Ficici, Emel , Mukerji, Ratul , Iuliano, James N , Ye, Jordan , Sanchez Garcia De Los Rios, Mateo , Bousquet, Hugo , Tan, May , Brathaban, Nivetha , Narasappa, Nell , Lu, Ya-Wen , Elechko, Jennifer , Maron, Maxim I , Phelps, Christopher B , Rahman, Jahan , Notti, Ryan Q , Sekeres, Samantha , Lamkin, Erica N , Bravo, Eduardo , Alencar, Alvaro J , Ewalt, Mark D , Islam, Prioty , Mato, Anthony , Roeker, Lindsey , Bhatt, Shruti , Taylor, Justin , Thompson, Meghan C , Hansen, Gwenn M , Abdel-Wahab, Omar , Lamkin, Erica , Ewalt, Mark D. , Roeker, Lindsey E. , Abdel‐Wahab, Omar

Cancer Discovery | July 22, 2026 | Volume: No volume available | Issue: No issue available | Pages: No page available

10.1158/2159-8290.cd-26-0251 | PMID 42484277 Get It

Abstract Early-phase clinical trials of Bruton’s tyrosine kinase (BTK) degraders have demonstrated efficacy in patients with BTK inhibitor-resistant chronic lymphocytic leukemia (CLL). How clinical resistance to BTK degraders arises is unknown. Here we sequenced serial CLL samples from patients enrolled in the phase I trials of zelebrudomide and bexobrutideg and observed recurrent expansion of preexisting BTK A428D mutations at relapse. Unlike previously studied BTK inhibitor resistance mutations, BTK A428D conferred pan-resistance to BTK inhibitors and degraders. In the absence of BTK-directed therapies, however, cells bearing BTK A428D exhibited a competitive disadvantage. A crystal structure of BTK A428D revealed that the mutant aspartate clashes with the adenine ring of ATP and the adenine-mimetic moiety of BTK inhibitors and degraders. Combining BTK degraders with venetoclax mitigated the expansion of BTK A428D. These results provide the molecular basis for clinical resistance to BTK degraders and will inform the development of next-generation BTK degrader therapies.
The blanking interval after atrial fibrillation ablation: time for reassessment with pulsed field energy—Authors’ reply
Rodriguez, Juan F. , Vemulapalli, Hema Srikanth , Kim, James Y. , Scott, Luis R. , Valverde, Arturo M. , Deshmukh, Abhishek , McLeod, Christopher J. , Srivathsan, Komandoor , Rodriguez-Riascos, Juan F , Vemulapalli, Hema S , Sardana, Mayank , Deshmukh, Abhishek J , Kapa, Suraj , McLeod, Christopher J , Srivathsan, Komandoor , Valverde, Arturo M , Kapa, Suraj

Europace | July 22, 2026 | Volume: 28 | Issue: 7 | Pages: No page available

10.1093/europace/euag165 | PMID 42481027 Get It