tbuckley/cabot-search huggingface dataset:
Local Receptor-interacting Protein Kinase 2 inhibition mitigates HDM-induced asthma
Authors: Daniel Alvarez-Simon, Saliha Ait Yahia, Camille Audousset, Martine Fanton d'Andon, Mathias Chamaillard, Ivo Gomperts Boneca, Anne Tsicopoulos
Journal: European Respiratory Journal (2024)

Background House dust mite is the most frequent trigger of allergic asthma, with innate and adaptive immune mechanisms playing critical roles in outcomes. We recently identified the nucleotide-binding oligomerisation domain 1 (NOD1)/receptor-interacting serine/threonine protein kinase 2 (RIPK2) signalling pathway as a relevant contributor to murine house dust mite-induced asthma. This study aimed to evaluate the effectiveness of a pharmacological RIPK2 inhibitor administered locally as a preventive and therapeutic approach using a house dust mite-induced asthma model in wild-type and humanised NOD1 mice harbouring an asthma-associated risk allele, and its relevance using air–liquid interface epithelial cultures from asthma patients. Methods A RIPK2 inhibitor was administered intranasally either preventively or therapeutically in a murine house dust mite-induced asthma model. Airway hyperresponsiveness, bronchoalveolar lavage composition, cytokine/chemokine expression and mucus production were evaluated, as well as the effect of the inhibitor on precision-cut lung slices. Furthermore, the inhibitor was tested on air–liquid interface epithelial cultures from asthma patients and controls. Results While local preventive administration of the RIPK2 inhibitor reduced airway hyperresponsiveness, eosinophilia, mucus production, T-helper type 2 cytokines and interleukin 33 (IL-33) in wild-type mice, its therapeutic administration failed to reduce the above parameters, except IL-33. By contrast, therapeutic RIPK2 inhibition mitigated all asthma features in humanised NOD1 mice. Results in precision-cut lung slices emphasised an early role of thymic stromal lymphopoietin and IL-33 in the NOD1-dependent response to house dust mite, and a late effect of NOD1 signalling on IL-13 effector response. RIPK2 inhibitor downregulated thymic stromal lymphopoietin and chemokines in house dust mite-stimulated epithelial cultures from asthma patients. Conclusion These data support that local interference of the NOD1 signalling pathway through RIPK2 inhibition may represent a new therapeutic approach in house dust mite-induced asthma.
Review of Systemic Lupus Erythematous—Reply
Authors: Caroline H. Siegel, Lisa R. Sammaritano
Journal: JAMA (2024)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2024 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Pulmonary Vein Isolation and Left Atrial Appendage Ligation in Atrial Fibrillation
Authors: Fangxiao Xia, Chao Su
Journal: JAMA (2024)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2024 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Self-Harm and Suicide Rates Before and After an Early Intervention Program for Patients With First-Episode Schizophrenia
Authors: Yi Chai, Jennifer Yee-Man Tang, Dennis Chak Fai Ma, Hao Luo, Sherry Kit Wa Chan
Journal: JAMA Network Open (2024)

Evidence on the association of early intervention services (EISs) with self-harm and suicide among patients with first-episode schizophrenia (FES) at older than 25 years is lacking.
Pulmonary Vein Isolation and Left Atrial Appendage Ligation in Atrial Fibrillation—Reply
Authors: Dhanunjaya R. Lakkireddy
Journal: JAMA (2024)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2024 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
<i>Notes from the Field:</i> Prevalence of Previous Dengue Virus Infection Among Children and Adolescents Aged 7–16 Years — American Samoa, September–October 2023
Authors: Sandra Kiplagat, Noelle Tavale, Adam Konrote, Astrid M. Johansson, Angelynn Papu, Janice Perez-Padilla, Forrest K. Jones, Hans Desale, Annette F. Ilimaleota, Jacki M. Tulafono, Mark Delorey, Emma Jones, Emi Chutaro, Janet Camacho, Freddy Medina, Rafael Tosado-Acevedo, Jorge L. Munoz-Jordan, Gabriela Paz-Bailey, Laura E. Adams, Motusa Tuileama Nua, Joshua M. Wong, Scott Anesi
Journal: MMWR Morbidity and Mortality Weekly Report (2024)
<i>Erratum:</i> Vol. 72, No. RR-6
Journal: MMWR Morbidity and Mortality Weekly Report (2024)

In the Recommendation and Report "CDC Guidelines for the Prevention and Treatment of Anthrax, 2023," multiple errors occurred.On page 32, in Table 7, and page 35, in Table 10, the imipenem/cilastatin dose should have read 1 g every 6 hours.On page 33, in the Abbreviations under Table 8, the abbreviation for PCN-S should have read penicillin-susceptible strains.On page 37, in Table 12, the clarithromycin dose should have read 7.5 mg/kg.On page 37, in Table 12, and page 38, in Table 13, the age range for the last two doses of moxifloxacin listed should have read ≥12 to <18 years.On page 39, in Table 13, and page 41, in Table 14, the first dose of AIGIV listed should have read <10 kg.On page 42, in Table 15; page 43, in Table 16; and page 45, in Table 17, the moxifloxacin dose in all columns should have read 10 mg/kg.On page 42, in Table 15, the amoxicillin dose should have read 25 mg/kg in all columns, and the linezolid dose in the 0 to <1 week columns should have read every 12 hours.On page 45, in Table 17, the omadacycline dose in the last three columns should have read 5.5 mg/kg loading dose IV × 1, then 3.85 mg/kg every 24 hours IV.
T-cell Responses to Individualized Neoantigen Therapy mRNA-4157 (V940) Alone or in Combination with Pembrolizumab in the Phase 1 KEYNOTE-603 Study
Authors: Justin F. Gainor, Manish R. Patel, Jeffrey S. Weber, Martin Gutierrez, Julie E. Bauman, Jeffrey M. Clarke, Ricklie Julian, Aaron J. Scott, Jessica L. Geiger, Kedar Kirtane, Celine Robert-Tissot, Brandon Coder, Moomal Tasneem, Jing Sun, Wei Zheng, Lauren Gerbereux, Andressa Laino, Filippos Porichis, Jack Russella Pollard, Peijie Hou, Vasudha Sehgal, Xing Chen, Manju Morrissey, Hikmat N. Daghestani, Igor Feldman, Lakshmi Srinivasan, Joshua P. Frederick, Michelle Brown, Praveen Aanur, Robert Meehan, Howard A. Burris
Journal: Cancer Discovery (2024)

Abstract mRNA-4157 (V940) is an individualized neoantigen therapy targeting up to 34 patient-specific tumor neoantigens to induce T-cell responses and potentiate antitumor activity. We report mechanistic insights into the immunogenicity of mRNA-4157 via characterization of T-cell responses to neoantigens from the first-in-human, phase 1, KEYNOTE-603 study (NCT03313778) in patients with resected non–small cell lung cancer (Part A: 1-mg mRNA-4157, n = 4) or resected cutaneous melanoma (Part D: 1-mg mRNA-4157 + 200-mg pembrolizumab, n = 12). Safety, tolerability, and immunogenicity were assessed. All patients experienced ≥1 treatment-emergent adverse event; there were no grade 4/5 adverse events or dose-limiting toxicities. mRNA-4157 alone induced consistent de novo and strengthened preexisting T-cell responses to targeted neoantigens. Following combination therapy, sustained mRNA-4157-induced neoantigen-specific T-cell responses and expansion of cytotoxic CD8 and CD4 T cells were observed. These findings show the potential of a novel mRNA individualized neoantigen therapy approach in oncology. Significance: The safety and immunogenicity results from this phase 1 study of mRNA-4157 as adjuvant monotherapy or combination therapy with pembrolizumab show generation of de novo and enhancement of existing neoantigen-specific T-cell responses and provide mechanistic proof of concept to support further development of mRNA-4157 for patients with resected solid tumors. See related commentary by Berraondo et al., p. 2021
Tyrosine-protein kinase SYK-related gene signature in baseline immune cells associated with adjuvant immunotherapy-induced immune-related adverse events in melanoma
Authors: Kelsey R. Monson, Robert Ferguson, Joanna E. Handzlik, Jiahan Xiong, Sasha Dagayev, Leah Morales, Vylyny Chat, Anabelle Bunis, Chaitra Sreenivasaiah, Sonia Dolfi, Daniel J. Tenney, Yongzhao Shao, Iman Osman, Jeffrey S. Weber, Tomas Kirchhoff
Journal: Clinical Cancer Research (2024)

Immune checkpoint inhibition (ICI) shows benefits in adjuvant (AT) and neoadjuvant melanoma treatments. However, ICI frequently induces severe immune-related adverse events (irAE). Unlike metastatic disease, in which irAEs are a clinical trade-off for treatment that improves survival, the toxicity burden from ICI in the AT setting is a substantial clinical problem urging for irAE-predictive biomarkers.
Mortality in the United States — Provisional Data, 2023
Authors: Farida B. Ahmad, Jodi A. Cisewski, Robert N. Anderson
Journal: MMWR Morbidity and Mortality Weekly Report (2024)

Final annual mortality data from the National Vital Statistics System for a given year are typically released 11 months after the end of the calendar year. Provisional data, which are based on preliminary death certificate data, provide an early estimate of deaths before the release of final data. In 2023, a provisional total of 3,090,582 deaths occurred in the United States. The age-adjusted death rate per 100,000 population was 884.2 among males and 632.8 among females; the overall rate, 750.4, was 6.1% lower than in 2022 (798.8). The overall rate decreased for all age groups. Overall age-adjusted death rates in 2023 were lowest among non-Hispanic multiracial (352.1) and highest among non-Hispanic Black or African American persons (924.3). The leading causes of death were heart disease, cancer, and unintentional injury. The number of deaths from COVID-19 (76,446) was 68.9% lower than in 2022 (245,614). Provisional death estimates provide an early signal about shifts in mortality trends. Timely and actionable data can guide public health policies and interventions for populations experiencing higher mortality.
Health and Economic Benefits of Routine Childhood Immunizations in the Era of the Vaccines for Children Program — United States, 1994–2023
Authors: Fangjun Zhou, Tara C. Jatlaoui, Andrew J. Leidner, Rosalind J. Carter, Xiaoyu Dong, Jeanne M. Santoli, Shannon Stokley, Demetre C. Daskalakis, Georgina Peacock
Journal: MMWR Morbidity and Mortality Weekly Report (2024)

Since 1994, the U.S. Vaccines for Children (VFC) program has covered the cost of vaccines for children whose families might not otherwise be able to afford vaccines. This report assessed and quantified the health benefits and economic impact of routine U.S. childhood immunizations among both VFC-eligible and non-VFC-eligible children born during 1994-2023. Diphtheria and tetanus toxoids and acellular pertussis vaccine; Haemophilus influenzae type b conjugate vaccine; oral and inactivated poliovirus vaccines; measles, mumps, and rubella vaccine; hepatitis B vaccine; varicella vaccine; pneumococcal conjugate vaccine; hepatitis A vaccine; and rotavirus vaccine were included. Averted illnesses and deaths and associated costs over the lifetimes of 30 annual cohorts of children born during 1994-2023 were estimated using established economic models. Net savings were calculated from the payer and societal perspectives. Among approximately 117 million children born during 1994-2023, routine childhood vaccinations will have prevented approximately 508 million lifetime cases of illness, 32 million hospitalizations, and 1,129,000 deaths, at a net savings of $540 billion in direct costs and $2.7 trillion in societal costs. From both payer and societal perspectives, routine childhood vaccinations among children born during 1994-2023 resulted in substantial cost savings. Childhood immunizations continue to provide substantial health and economic benefits, while promoting health equity.
Depressive Symptoms Across Childhood and Adolescence and Adult Psychosocial Outcomes
Authors: Natan J. Vega Potler
Journal: JAMA Network Open (2024)

Lamprini Psychogiou, PhD; Marie C. Navarro, PhD; Massimiliano Orri, PhD; Sylvana M. Côté, PhD; Marilyn N. Ahun, PhD
How Should Organizations Be Held Accountable for Clinician Well-Being?
Authors: Jonathan Ripp, Tait Shanafelt
Journal: JAMA (2024)

This Viewpoint summarizes methods used by health care organizations to assess and improve clinician well-being, discusses the potential downsides of public reporting of clinician well-being survey data, and calls for making organizations’ adherence to structure and process measures a part of accreditation criteria.
Oral Antibiotics and Risk of Serious Cutaneous Adverse Drug Reactions
Authors: Erika Y. Lee, Tara Gomes, Aaron M. Drucker, Nick Daneman, Ayesha Asaf, Fangyun Wu, Vincent Piguet, David N. Juurlink
Journal: JAMA (2024)

Serious cutaneous adverse drug reactions (cADRs) are potentially life-threatening drug hypersensitivity reactions involving the skin and internal organs. Antibiotics are a recognized cause of these reactions, but no studies have compared relative risks across antibiotic classes.
Antiseizure Drugs and Pharmacogenetics—Is There Signal in the Noise?
Authors: David J. Gagnon
Journal: JAMA Network Open (2024)

Filip Milosavljević, PharmM, PhD; Marina Manojlović, PharmM; Lena Matković, MD; Espen Molden, PharmM, PhD; Magnus Ingelman-Sundberg, PhD; Stefan Leucht, MD, PhD; Marin M. Jukić, PharmM, PhD
Alopecia areata exhibits cutaneous and systemic <scp>OX</scp>40 activation across atopic backgrounds
Authors: Madeline Kim, Ester Del Duca, Dante Dahabreh, Daniel Lozano‐Ojalvo, Britta Carroll, Meredith Manson, Swaroop Bose, Digpal Gour, Monali NandyMazumdar, Ying Liu, Mitchelle Yu Ekey, Amira Chowdhury, Michael Angelov, Benjamin Ungar, Yeriel Estrada, Emma Guttman‐Yassky
Journal: Allergy (2024)

Abstract Background Alopecia areata (AA) is a chronic, nonscarring hair‐loss disorder associated with significant quality‐of‐life impairment and limited treatment options. AA has been recently linked to atopy and shown to exhibit both Th1‐ and Th2‐driven inflammation. However, a comprehensive molecular and cellular characterization across blood and scalp compartments in both atopic and nonatopic patients is lacking. Methods Lesional and nonlesional scalp biopsies obtained from AA patients with ( n = 16) or without ( n = 20) atopic history, and 17 demographically matched healthy controls were analyzed with RNA‐seq, RT‐PCR, and immunohistochemistry. Flow cytometry was also performed on peripheral blood mononuclear cells (PBMCs) from a subset of patients. Differential expression was defined using |fold‐change| &gt; 1.5 and false‐discovery rate &lt;0.05. Results AA scalp exhibited robust upregulation of Th1‐ ( IFNG , CXCL9 , CXCL10 , CXCL11 ) and Th2‐related products ( CCL26 , CCR4 , IL10 , IL13 , TSLP , TNFRSF4 /OX40) and shared downregulation of hair keratins, regardless of atopic background, with variable Th17/Th22 modulation. AA patients with atopy exhibited greater inflammatory tone and Th2‐skewing ( IL10 , IL13 , IL33 , CCR4 , CCL26 ). Disease severity correlated significantly with immune and hair keratin biomarkers and with perifollicular cellular infiltrates. Cutaneous OX40/OX40L upregulation was paralleled by increases in circulating OX40 + and OX40L + leukocytes, regardless of atopic background. Conclusion Our results suggest some atopy‐associated immune differences in AA and highlight the OX40 axis as a potential novel therapeutic target that may broadly benefit AA patients.
Tumor-secreted extracellular vesicles counteract therapy response by triggering inflammatory mesenchymal stem cell development
Authors: Crescenzo Massaro, Hilal N. Sensoy, Manon Mulders, Celine De Schrijver, Cristina Gómez-Martín, Juan Simon Nieto, Tonny Lagerweij, Alisha Atmopawiro, Jennifer Pérez-Boza, Maarten Bebelman, Leontien Bosch, Simone Foderaro, Mafalda Neves Ferreira, Monique A.J. van Eijndhoven, Jan R.T. van Weering, Carmela Dell’Aversana, Lucia Altucci, Cemile Dilara Savci-Heijink, Niels W.C.J. van de Donk, Cristina Giorgio, Laura Brandolini, Marcello Allegretti, Dirk Michiel Pegtel, Serena Rubina Baglio
Journal: Clinical Cancer Research (2024)

Abstract Purpose: Therapy resistance is a major clinical hurdle in bone cancer treatment and seems to be largely driven by poorly understood microenvironmental factors. Recent evidence suggests a critical role for a unique subpopulation of mesenchymal stem cells with inflammatory features (iMSC), though their origin and function remained unexplored. We demonstrate that cancer-secreted extracellular vesicles (EV) trigger the development of iMSCs, which hinder therapy response in vivo, and set out to identify strategies to counteract their function. Experimental Design: The role of iMSCs in therapy resistance was evaluated in an orthotopic xenograft mouse model of osteosarcoma. EV-induced alterations of the MSC transcriptome were analyzed and compared with single-cell RNA sequencing data of biopsies from patients with osteosarcoma and multiple myeloma. Functional assays identified EV components driving iMSC development. We assessed the efficacy of clinical drugs in blocking iMSC-induced resistance in vivo. Results: We found that iMSCs are induced by interaction with cancer EVs and completely abrogate the antimetastatic effect of TGFβ signaling inhibition. Importantly, EV-induced iMSCs faithfully recapitulate the inflammatory single-cell RNA signature of stromal cells enriched in biopsies from patients with multiple myeloma and osteosarcoma. Mechanistically, cancer EVs act through two distinct mechanisms. EV-associated TGFβ induces IL6 production, whereas the EV-RNA cargo enhances TLR3-mediated chemokine production. We reveal that simultaneous blockade of downstream EV-activated pathways with ladarixin and tocilizumab disrupts metastasis formation and overcomes iMSC-induced resistance. Conclusions: Our observations establish iMSCs as major contributors to drug resistance, reveal EVs as triggers of iMSC development, and highlight a promising combination strategy to improve therapy response in patients with bone cancer.
Functional relay between Mph(A) enzyme and Mrx efflux pump mediates azithromycin resistance, a novel mechanism of bacterial antimicrobial resistance
Authors: Xuemei Yang, Haoshuai Zhang, Yang Tang, Heng Heng, Yan-Chu Cheung, Xuejiao Song, Hang-Kin Kong, Edward Wai-Chi Chan, Sheng Chen
Journal: Drug Resistance Updates (2024)
Abiraterone, Olaparib, or Abiraterone + Olaparib in First-line Metastatic Castration-Resistant Prostate Cancer with DNA Repair Defects (BRCAAway)
Authors: Maha Hussain, Masha Kocherginsky, Neeraj Agarwal, Nabil Adra, Jingsong Zhang, Channing J. Paller, Joel Picus, Zachery R. Reichert, Russell Z. Szmulewitz, Scott T. Tagawa, Timothy M. Kuzel, Latifa A. Bazzi, Stephanie Daignault-Newton, Young E. Whang, Robert Dreicer, Ryan D. Stephenson, Matthew B. Rettig, Daniel Shevrin, Travis Gerke, Arul M. Chinnaiyan, Emmanuel S. Antonarakis
Journal: Clinical Cancer Research (2024)

Abstract Purpose: Deleterious germline/somatic homologous recombination repair mutations (HRRm) are present in ∼25% of patients with metastatic castration-resistant prostate cancer (mCRPC). Preclinically, poly(ADP-ribose) polymerase (PARP) inhibition demonstrated synergism with androgen receptor pathway (ARP)–targeted therapy. This trial evaluated the efficacy of ARP inhibitor versus PARP inhibitor versus their combination as first-line therapy in patients with mCRPC with HRRms. Patients and Methods: BRCAAway is a biomarker preselected, randomized, phase 2 trial. Patients with BRCA1/2 and/or ATM alterations were randomized 1:1:1 to Arm1: abiraterone (1,000 mg)/prednisone (5 mg BID) (Abi/pred), Arm2: olaparib (300 mg BID) (Ola), or Arm3: abiraterone/prednisone + olaparib (Abi/pred + Ola). Single-agent arms could cross over at progression. Exploratory Arm4 patients with other HRRms received olaparib alone. The primary endpoint was progression-free survival (PFS), and secondary endpoints were objective response, PSA response, and safety. Results: Sixty-one of 165 eligible patients had BRCA1/2 or ATM mutations: median age: 67 (IQR, 62–73) years. Mutations: BRCA1 n = 3, BRCA2 n = 46, ATM n = 11, and multiple n = 1; 33 germline and 28 somatic mutations. Median PFS [95% confidence interval (CI)]: Abi/pred, 8.6 months (m; 2.9, 17), Ola, 14 m (8.4, 20), and Abi/pred + Ola, 39 m [22, not reached (NR)]. There were no G4/5 adverse events; 8/19 patients on Abi/pred treatment crossed over to Ola, and 8/21 vice versa. Median PFS (95% CI) from crossover: Ola-after-Abi/pred, 8.3 m (5.5, 15) and Abi/pred-after-Ola, 7.2 m (2.8, NR). Median PFS (95% CI) from randomization: Ola-after-Abi/pred, 16 m (7.8, 25) and Abi/pred-after-Ola, 16 m (11, NR). Seventeen of 165 patients with other HRRms received olaparib: median PFS (95% CI): 5.5 m (2, 11). Conclusions: In patients with mCRPC with BRCA1/2 or ATM HRRm, Abi/pred + Ola was well tolerated and demonstrated longer PFS versus either agent alone or sequentially.