tbuckley/cabot-search huggingface dataset:
Adjuvant Abemaciclib Plus Endocrine Therapy for Hormone Receptor–Positive, Human Epidermal Growth Factor Receptor 2–Negative, High-Risk Early Breast Cancer: Results From a Preplanned monarchE Overall Survival Interim Analysis, Including 5-Year Efficacy Outcomes
Authors: Priya Rastogi, Joyce O'Shaughnessy, Miguel Martin, Frances Boyle, Javier Cortes, Hope S. Rugo, Matthew P. Goetz, Erika P. Hamilton, Chiun-Sheng Huang, Elzbieta Senkus, Alexey Tryakin, Irfan Cicin, Laura Testa, Patrick Neven, Jens Huober, Zhimin Shao, Ran Wei, Valérie André, Maria Munoz, Belen San Antonio, Ashwin Shahir, Nadia Harbeck, Stephen Johnston
Journal: Journal of Clinical Oncology (2024)

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical trial updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported. Two years of adjuvant abemaciclib combined with endocrine therapy (ET) resulted in a significant improvement in invasive disease-free survival (IDFS) and distant relapse-free survival (DRFS) that persisted beyond the 2-year treatment period in patients with hormone receptor–positive, human epidermal growth factor receptor 2–negative, node-positive, high-risk early breast cancer (EBC). Here, we report 5-year efficacy results from a prespecified overall survival (OS) interim analysis. In the intent-to-treat population, with a median follow-up of 54 months, the benefit of abemaciclib was sustained with hazard ratios of 0.680 (95% CI, 0.599 to 0.772) for IDFS and 0.675 (95% CI, 0.588 to 0.774) for DRFS. This persistence of abemaciclib benefit translated to continuous separation of the curves with a deepening in 5-year absolute improvement in IDFS and DRFS rates of 7.6% and 6.7%, respectively, compared with rates of 6% and 5.3% at 4 years and 4.8% and 4.1% at 3 years. With fewer deaths in the abemaciclib plus ET arm compared with the ET-alone arm (208 v 234), statistical significance was not reached for OS. No new safety signals were observed. In conclusion, abemaciclib plus ET continued to reduce the risk of developing invasive and distant disease recurrence beyond the completion of treatment. The increasing absolute improvement at 5 years is consistent with a carryover effect and further supports the use of abemaciclib in patients with high-risk EBC.
Long-Term Follow-Up of the RESORT Study (E4402): A Randomized Phase III Comparison of Two Different Rituximab Dosing Strategies for Low–Tumor Burden Follicular Lymphoma
Authors: Brad S. Kahl, Opeyemi A. Jegede, Christopher Peterson, Lode J. Swinnen, Thomas M. Habermann, Stephen J. Schuster, Matthias Weiss, Paul A. Fishkin, Timothy S. Fenske, Michael E. Williams
Journal: Journal of Clinical Oncology (2024)

JCO
DNA Damage Response Pharmacogenomic (DDR_PGx) Score Predicts Response to Chemotherapy Consisting of Gemtuzumab Ozogamicin in Pediatric AML: A Report from the Children's Oncology Group
Authors: Vivek M. Shastri, Lata Chauhan, Mohammed Gbadamosi, Todd A. Alonzo, Yi-Cheng Wang, Richard Aplenc, Betsy A. Hirsch, Edward A. Kolb, Alan S. Gamis, Soheil Meshinchi, Jatinder K. Lamba
Journal: Clinical Cancer Research (2024)

Comprehensive pharmacogenomics (PGx) evaluation of calicheamicin-pathway to identify predictive PGx markers of response to gemtuzumab ozogamicin (GO) treatment in acute myeloid leukemia (AML).
A federated learning system for precision oncology in Europe: DigiONE
Authors: Piers Mahon, Ismini Chatzitheofilou, Andre Dekker, Xosé Fernández, Geoff Hall, Aslaug Helland, Alberto Traverso, Cedric Van Marcke, Janne Vehreschild, Gennaro Ciliberto, Giovanni Tonon
Journal: Nature Medicine (2024)
Noncoding mutations drive persistence of a founder preleukemic clone which initiates late relapse in T-ALL
Authors: David O’Connor, Jose Espejo Valle-Inclán, Lucia Conde, Gianna Bloye, Sunniyat Rahman, Joana R. Costa, Jack Bartram, Stuart Adams, Gary Wright, Hillary Elrick, Kerry Wall, Sara Dyer, Christopher Howell, Galina Jigoulina, Javier Herrero, Isidro Cortes-Ciriano, Anthony V. Moorman, Marc R. Mansour
Journal: Blood (2024)
Amanda
Authors: James Austin
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
Clinical and functional spectrum of RAC2-related immunodeficiency
Authors: Ágnes Donkó, Svetlana O. Sharapova, Juraj Kabat, Sundar Ganesan, Fabian H. Hauck, Jenna R. E. Bergerson, Louis Marois, Jordan Abbott, Despina Moshous, Kelli W. Williams, Nicholas Campbell, Paul L. Martin, Chantal Lagresle-Peyrou, Timothy Trojan, Natalia B. Kuzmenko, Ekaterina A. Deordieva, Elena V. Raykina, Michael S. Abers, Hassan Abolhassani, Vincent Barlogis, Carlos Milla, Geoffrey Hall, Talal Mousallem, Joseph Church, Neena Kapoor, Guilhem Cros, Hugo Chapdelaine, Clara Franco-Jarava, Ingrid Lopez-Lerma, Maurizio Miano, Jennifer W. Leiding, Christoph Klein, Marie José Stasia, Alain Fischer, Kuang-Chih Hsiao, Timi Martelius, Mikko R. J. Sepännen, Sara Barmettler, Jolan Walter, Tania N. Masmas, Anna A. Mukhina, Emilia Liana Falcone, Sven Kracker, Anna Shcherbina, Steven M. Holland, Thomas L. Leto, Amy P. Hsu
Journal: Blood (2024)
Genomic Classification and Individualized Prognosis in Multiple Myeloma
Authors: Francesco Maura, Arjun Raj Rajanna, Bachisio Ziccheddu, Alexandra M. Poos, Andriy Derkach, Kylee Maclachlan, Michael Durante, Benjamin Diamond, Marios Papadimitriou, Faith Davies, Eileen M. Boyle, Brian Walker, Malin Hultcrantz, Ariosto Silva, Oliver Hampton, Jamie K. Teer, Erin M. Siegel, Niccolò Bolli, Graham H. Jackson, Martin Kaiser, Charlotte Pawlyn, Gordon Cook, Dickran Kazandjian, Caleb Stein, Marta Chesi, Leif Bergsagel, Elias K. Mai, Hartmut Goldschmidt, Katja C. Weisel, Roland Fenk, Marc S. Raab, Fritz Van Rhee, Saad Usmani, Kenneth H. Shain, Niels Weinhold, Gareth Morgan, Ola Landgren
Journal: Journal of Clinical Oncology (2024)

PURPOSE Outcomes for patients with newly diagnosed multiple myeloma (NDMM) are heterogenous, with overall survival (OS) ranging from months to over 10 years. METHODS To decipher and predict the molecular and clinical heterogeneity of NDMM, we assembled a series of 1,933 patients with available clinical, genomic, and therapeutic data. RESULTS Leveraging a comprehensive catalog of genomic drivers, we identified 12 groups, expanding on previous gene expression–based molecular classifications. To build a model predicting individualized risk in NDMM (IRMMa), we integrated clinical, genomic, and treatment variables. To correct for time-dependent variables, including high-dose melphalan followed by autologous stem-cell transplantation (HDM-ASCT), and maintenance therapy, a multi-state model was designed. The IRMMa model accuracy was significantly higher than all comparator prognostic models, with a c-index for OS of 0.726, compared with International Staging System (ISS; 0.61), revised-ISS (0.572), and R2-ISS (0.625). Integral to model accuracy was 20 genomic features, including 1q21 gain/amp, del 1p, TP53 loss, NSD2 translocations, APOBEC mutational signatures, and copy-number signatures (reflecting the complex structural variant chromothripsis). IRMMa accuracy and superiority compared with other prognostic models were validated on 256 patients enrolled in the GMMG-HD6 (ClinicalTrials.gov identifier: NCT02495922 ) clinical trial. Individualized patient risks were significantly affected across the 12 genomic groups by different treatment strategies (ie, treatment variance), which was used to identify patients for whom HDM-ASCT is particularly effective versus patients for whom the impact is limited. CONCLUSION Integrating clinical, demographic, genomic, and therapeutic data, to our knowledge, we have developed the first individualized risk-prediction model enabling personally tailored therapeutic decisions for patients with NDMM.
BCMA- or GPRC5D-targeting bispecific antibodies in multiple myeloma: efficacy, safety, and resistance mechanisms
Authors: Holly Lee, Paola Neri, Nizar J. Bahlis
Journal: Blood (2024)

Bispecific antibodies that engage T cells to target B-cell maturation antigen or G-protein-coupled receptor class C group 5 member D have demonstrated remarkable efficacy in heavily pretreated relapsed or refractory multiple myeloma (MM), leading to the recent accelerated approval of teclistamab, elranatamab, and talquetamab by health agencies. Future challenges, however, remain to define their optimal dosing schedule and duration, sequencing, and integration with established anti-MM therapeutics as well as delineating the biological and clinical mediators of immune escape.
Rammya Mathew: We risk creating a lost tribe of GPs
Authors: Rammya Mathew
Journal: BMJ (2024)

Rammya Mathew: We risk creating a lost tribe of GPs Rammya Mathew GPFor the past 10 years the general practice workforce has been flooded with locum GPs.Many practices were unable to recruit salaried employees and instead were paying a premium for locum GPs to provide enough appointments to meet the needs of their patient list.In the past few months, however, I'm hearing stories from locum GPs who can no longer find work and are struggling.
Twenty-year-old patient with polyarthritis since childhood showing cysts and ground glass attenuation on HRCT
Authors: Marília da Cruz Fagundes, Thais Bianco, Daniella Porfírio Nunes, Tayza Katelline Danilau Ostroski, Guilherme das Posses Bridi, Alexandre Melo Kawassaki, Carmen Silvia Valente Barbas, Leonardo Oliveira Mendonça, Samar Freschi Barros, Jorge Kalil, Anthony K Shum, Dante Luiz Escuissato
Journal: Thorax (2024)
Autotaxin–lysolipid signaling suppresses a CCL11–eosinophil axis to promote pancreatic cancer progression
Authors: Sohinee Bhattacharyya, Chet Oon, Luis Diaz, Holly Sandborg, Erin S. Stempinski, Michelle Saoi, Terry K. Morgan, Claudia S. López, Justin R. Cross, Mara H. Sherman
Journal: Nature Cancer (2024)

Abstract Lipids and their modifying enzymes regulate diverse features of the tumor microenvironment and cancer progression. The secreted enzyme autotaxin (ATX) hydrolyzes extracellular lysophosphatidylcholine to generate the multifunctional lipid mediator lysophosphatidic acid (LPA) and supports the growth of several tumor types, including pancreatic ductal adenocarcinoma (PDAC). Here we show that ATX suppresses the accumulation of eosinophils in the PDAC microenvironment. Genetic or pharmacologic ATX inhibition increased the number of intratumor eosinophils, which promote tumor cell apoptosis locally and suppress tumor progression. Mechanistically, ATX suppresses eosinophil accumulation via an autocrine feedback loop, wherein ATX–LPA signaling negatively regulates the activity of the AP-1 transcription factor c-Jun, in turn suppressing the expression of the potent eosinophil chemoattractant CCL11 (eotaxin-1). Eosinophils were identified in human PDAC specimens, and rare individuals with high intratumor eosinophil abundance had the longest overall survival. Together with recent findings, this study reveals the context-dependent, immune-modulatory potential of ATX–LPA signaling in cancer.
Health effects associated with exposure to secondhand smoke: a Burden of Proof study
Authors: Luisa S. Flor, Jason A. Anderson, Noah Ahmad, Aleksandr Aravkin, Sinclair Carr, Xiaochen Dai, Gabriela F. Gil, Simon I. Hay, Matthew J. Malloy, Susan A. McLaughlin, Erin C. Mullany, Christopher J. L. Murray, Erin M. O’Connell, Chukwuma Okereke, Reed J. D. Sorensen, Joanna Whisnant, Peng Zheng, Emmanuela Gakidou
Journal: Nature Medicine (2024)

Abstract Despite a gradual decline in smoking rates over time, exposure to secondhand smoke (SHS) continues to cause harm to nonsmokers, who are disproportionately children and women living in low- and middle-income countries. We comprehensively reviewed the literature published by July 2022 concerning the adverse impacts of SHS exposure on nine health outcomes. Following, we quantified each exposure–response association accounting for various sources of uncertainty and evaluated the strength of the evidence supporting our analyses using the Burden of Proof Risk Function methodology. We found all nine health outcomes to be associated with SHS exposure. We conservatively estimated that SHS increases the risk of ischemic heart disease, stroke, type 2 diabetes and lung cancer by at least around 8%, 5%, 1% and 1%, respectively, with the evidence supporting these harmful associations rated as weak (two stars). The evidence supporting the harmful associations between SHS and otitis media, asthma, lower respiratory infections, breast cancer and chronic obstructive pulmonary disease was weaker (one star). Despite the weak underlying evidence for these associations, our results reinforce the harmful effects of SHS on health and the need to prioritize advancing efforts to reduce active and passive smoking through a combination of public health policies and education initiatives.
Breaking NGF–TrkA immunosuppression in melanoma sensitizes immunotherapy for durable memory T cell protection
Authors: Tao Yin, Guoping Wang, Liuyang Wang, Poorva Mudgal, Ergang Wang, Christopher C. Pan, Peter B. Alexander, Haiyang Wu, Chengjie Cao, Yaosi Liang, Lianmei Tan, De Huang, Mengyang Chong, Rui Chen, Bryan Jian Wei Lim, Kun Xiang, Wei Xue, Lixin Wan, Hailan Hu, Yuin-Han Loh, Xiao-Fan Wang, Qi-Jing Li
Journal: Nature Immunology (2024)
Health Care Transitions Among Adolescents and Young Adults With Cancer
Authors: Matthew J. Ehrhardt, Danielle Novetsky Friedman, Melissa M. Hudson
Journal: Journal of Clinical Oncology (2024)

Survivors of adolescent and young adult (AYA) cancers, defined as individuals diagnosed with a primary malignancy between age 15 and 39 years, are a growing population with unique developmental, psychosocial, and health-related needs. These individuals are at excess risk of developing a wide range of chronic comorbidities compared with the general population and, therefore, require lifelong, risk-based, survivorship care to optimize long-term health outcomes. The health care needs of survivors of AYA cancers are particularly complicated given the often heterogeneous and sometimes fragmented care they receive throughout the cancer care continuum. For example, AYA survivors are often treated in disparate settings (pediatric v adult) on dissimilar protocols that include different recommendations for longitudinal follow-up. Specialized tools and techniques are needed to ensure that AYA survivors move seamlessly from acute cancer care to survivorship care and, in many cases, from pediatric to adult clinics while still remaining engaged in long-term follow-up. Systematic, age-appropriate transitional practices involving well-established clinical models of care, survivorship care plans, and survivorship guidelines are needed to facilitate effective transitions between providers. Future studies are necessary to enhance and optimize the clinical effectiveness of transition processes in AYA cancer survivors.
Reprogramming tumor-associated macrophages by a dually targeted milk exosome system as a potent monotherapy for cancer
Authors: Ying Chen, Liang Gong, Yulin Cao, Zhiang Liu, Yuanben Wang, Han Cheng, Yuyang Feng, Surui Yao, Yuan Yin, Zhimeng Wu, Zhaohui Huang
Journal: Journal of Controlled Release (2024)
Noninvasive Detection of Neuroendocrine Prostate Cancer through Targeted Cell-free DNA Methylation
Authors: Gian Marco Franceschini, Orsetta Quaini, Kei Mizuno, Francesco Orlando, Yari Ciani, Sheng-Yu Ku, Michael Sigouros, Emily Rothmann, Alicia Alonso, Matteo Benelli, Caterina Nardella, Joonghoon Auh, Dory Freeman, Brian Hanratty, Mohamed Adil, Olivier Elemento, Scott T. Tagawa, Felix Y. Feng, Orazio Caffo, Consuelo Buttigliero, Umberto Basso, Peter S. Nelson, Eva Corey, Michael C. Haffner, Gerhardt Attard, Ana Aparicio, Francesca Demichelis, Himisha Beltran
Journal: Cancer Discovery (2023)

Castration-resistant prostate cancer (CRPC) is a heterogeneous disease associated with phenotypic subtypes that drive therapy response and outcome differences. Histologic transformation to castration-resistant neuroendocrine prostate cancer (CRPC-NE) is associated with distinct epigenetic alterations, including changes in DNA methylation. The current diagnosis of CRPC-NE is challenging and relies on metastatic biopsy. We developed a targeted DNA methylation assay to detect CRPC-NE using plasma cell-free DNA (cfDNA). The assay quantifies tumor content and provides a phenotype evidence score that captures diverse CRPC phenotypes, leveraging regions to inform transcriptional state. We tested the design in independent clinical cohorts (n = 222 plasma samples) and qualified it achieving an AUC > 0.93 for detecting pathology-confirmed CRPC-NE (n = 136). Methylation-defined cfDNA tumor content was associated with clinical outcomes in two prospective phase II clinical trials geared towards aggressive variant CRPC and CRPC-NE. These data support the application of targeted DNA methylation for CRPC-NE detection and patient stratification. Neuroendocrine prostate cancer is an aggressive subtype of treatment-resistant prostate cancer. Early detection is important, but the diagnosis currently relies on metastatic biopsy. We describe the development and validation of a plasma cell-free DNA targeted methylation panel that can quantify tumor fraction and identify patients with neuroendocrine prostate cancer noninvasively. This article is featured in Selected Articles from This Issue, p. 384.
Clearing soluble MIC reverses the impaired function of natural killer cells from patients with multiple myeloma
Authors: Sojeong Kim, Haerim Chung, Jeong-Eun Kwak, Yu Ri Kim, Chung Hyun Park, Yeonhee Kim, June-Won Cheong, Jennifer Wu, Eui-Cheol Shin, Hyunsoo Cho, Jin Seok Kim
Journal: Journal for ImmunoTherapy of Cancer (2024)

Background Major histocompatibility complex (MHC) class I chain-related protein (MIC) is a stress-induced ligand released from multiple myeloma (MM) cells during progression, and soluble MIC impairs natural killer group 2D (NKG2D) activating receptor-mediated recognition and function of natural killer (NK) cells. However, whether clearing soluble MIC with a monoclonal antibody (mAb) can restore NK cell activity of MM patients remains undetermined. Methods We analyzed The Cancer Genome Atlas (TCGA) Multiple Myeloma Research Foundation (MMRF) CoMMpass data set to examine the prognostic significance of MIC expression in MM. We examined the level of soluble MIC in paired peripheral blood (PB) and bone marrow (BM) plasma of patients with MM at diagnosis by ELISA. We evaluated the correlation between the level of soluble MIC and immunophenotype of NK cells from MM patients by multicolor flow cytometry. We also generated MIC-overexpressing MM cell line and characterized the cytotoxic function of patient NK cells in the presence of soluble MIC, and examined the impact of clearing soluble MIC with a humanized mAb (huB10G5). Results We characterize the importance of MICA in MM by revealing the significantly better overall survival of patients with high MICA expression from TCGA MMRF CoMMpass data set. The level of soluble MICA is more highly elevated in MM than in precursor stages, and the concentration of soluble MICA is higher in BM plasma than in PB. The concentration of soluble MICA in BM was correlated with myeloma burden, while it was negatively correlated with the frequency of NKG2D + NK cells in diagnostic BM aspirates of MM patients. Soluble MICA downregulated NKG2D expression and decreased cytotoxicity of MM patient NK cells ex vivo , which were reversed by a humanized soluble MIC-clearing mAb (huB10G5) with enhanced degranulation of NK cells. Conclusions Our findings indicate targeting soluble MIC with huB10G5 might be a viable therapeutic approach to promote NKG2D-dependent cellular immunotherapy outcome in MM.
Unanswered questions following reports of secondary malignancies after CAR-T cell therapy
Authors: Bruce L. Levine, Marcelo C. Pasquini, John E. Connolly, David L. Porter, Michael P. Gustafson, Jaap J. Boelens, Edwin M. Horwitz, Stephan A. Grupp, Marcela V. Maus, Frederick L. Locke, Fabio Ciceri, Annalisa Ruggeri, John Snowden, Helen E. Heslop, Crystal L. Mackall, Carl H. June, Anna M. Sureda, Miguel-Angel Perales
Journal: Nature Medicine (2024)
Guided bone regeneration in implant dentistry: Basic principle, progress over 35 years, and recent research activities
Authors: Daniel Buser, Istvan Urban, Alberto Monje, Marcel F. Kunrath, Christer Dahlin
Journal: Periodontology 2000 (2023)

Abstract Bone augmentation procedures are frequent today in implant patients, since an implant should be circumferentially anchored in bone at completion of bone healing to have a good long‐term stability. The best documented surgical technique to achieve this goal is guided bone regeneration (GBR) utilizing barrier membranes in combination with bone fillers. This clinical review paper reflects 35 years of development and progress with GBR. In the 1990s, GBR was developed by defining the indications for GBR, examining various barrier membranes, bone grafts, and bone substitutes. Complications were identified and reduced by modifications of the surgical technique. Today, the selection criteria for various surgical approaches are much better understood, in particular, in post‐extraction implant placement. In the majority of patients, biodegradable collagen membranes are used, mainly for horizontal bone augmentation, whereas bioinert PTFE membranes are preferred for vertical ridge augmentation. The leading surgeons are using a composite graft with autogenous bone chips to accelerate bone formation, in combination with a low‐substitution bone filer to better maintain the augmented bone volume over time. In addition, major efforts have been made since the millenium change to reduce surgical trauma and patient morbidity as much as possible. At the end, some open questions related to GBR are discussed.
Lactate administration improves laboratory parameters in murine models of iron overload
Authors: Wei Liu, Yue Wu, Huaiqing Wei, Juan Ma, Wenya Feng, Qiuyuan Yang, Shuping Zhang, Tomas Ganz, Sijin Liu
Journal: Blood (2024)

Current iron overload therapeutics have inherent drawbacks including perpetuated low hepcidin. Here, we unveiled that lactate, a potent hepcidin agonist, effectively reduced serum and hepatic iron levels in mouse models of iron overload with an improved erythropoiesis in β-thalassemic mice.
Prevalence &amp; Odds of Anxiety &amp; Depression in Cutaneous Malignant Melanoma: A Proportional Meta-analysis &amp; Regression
Authors: Garikai Kungwengwe, Chloe Gowthorpe, Stephen R Ali, Harry Warren, Damien J Drury, Ky-Leigh Ang, John A G Gibson, Thomas D Dobbs, Iain S Whitaker
Journal: British Journal of Dermatology (2024)

The psychological burden of cutaneous malignant melanoma (CM) is all-encompassing, affecting treatment adherence, recurrence and mortality. However, the prevalence and risk factors of anxiety and depression in CM remain unclear.