tbuckley/cabot-search huggingface dataset:
Abstract IA12: From mouse to man: Dissecting cancer mechanisms using mouse models
Authors: Cory Abate-Shen
Journal: Cancer Research (2020)

Abstract I have a longstanding interest in understanding how basic cellular mechanisms become co-opted in cancer. I have approached this problem by studying the transcriptional regulatory mechanisms of homeobox genes with the goal of understanding their roles in development, differentiation, and cancer. Over the years, my research program has evolved towards its current focus in which we have undertaken a multidisciplinary approach to investigate genitourinary malignancies, which includes using mechanism-based studies, analyses of genetically engineered mouse models (GEMMs), and state-of-the-art systems biology approaches. My research focus on prostate cancer has its origins in our discovery of Nkx3.1, a prostate-specific homeobox gene that is essential for prostate differentiation and whose loss of function predisposes to prostate cancer. The culmination of our studies over many years has led to a model in which NKX3.1 functions as a gatekeeper that promotes prostate differentiation and protects against prostate cancer initiation. Our recent work has shown that Nkx3.1 is sufficient to fully reprogram non-prostate epithelium to form prostate in vivo. Our work showing that Nkx3.1 mutant mice accurately model indolent prostate cancer led to the discovery of a 3-gene panel that distinguishes indolent and aggressive human prostate cancers, which we are now advancing to the clinic. Moreover, our coclinical prevention study of Nkx3.1 mutant mice led to the identification of a gene signature that predicts response to antiandrogens for men on active surveillance. Furthermore, our analysis of Nkx3.1 mutant mice provided the foundation for our extensive series of GEMMs that are based on genomic alterations that are prevalent in human prostate cancer and that represent the full spectrum of prostate cancer phenotypes, ranging from preinvasive to lethal metastatic disease. To capitalize on these GEMMs, we have generated genome-wide regulatory networks for mouse and human prostate cancer, which have enabled cross-species analyses that have identified key drivers of the specific stages of prostate cancer. We have expanded these computational approaches to integrate preclinical data from GEMMs with human clinical data to predict drug response and optimize drug combinations for human prostate cancer. These studies have identified cellular plasticity as a mechanism of drug resistance in prostate cancer. Citation Format: Cory Abate-Shen. From mouse to man: Dissecting cancer mechanisms using mouse models [abstract]. In: Proceedings of the AACR Special Conference on the Evolving Landscape of Cancer Modeling; 2020 Mar 2-5; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2020;80(11 Suppl):Abstract nr IA12.
Ibrutinib dose modifications in the management of CLL
Authors: Camille Hardy-Abeloos, Rachel Pinotti, Janice Gabrilove
Journal: Journal of Hematology & Oncology (2020)

Ibrutinib is a Bruton tyrosine kinase inhibitor approved for the treatment of chronic lymphocytic leukemia (CLL) in 2014. Ibrutinib is often used to treat patients who are younger than the patients originally included in theclinical trials have additional unfavorable prognostic factors and suffer from additional comorbidities excluded from the original phase III trials. Our objective was to examine current clinical practices and their impact in this expanded population of CLL patients who often require adjustments in the standard prescribed dose and schedule of therapy.An extensive review of the medical literature was conducted to establish the consensus on ibrutinib dose modifications in patients with CLL. Twenty-nine studies were reviewed including fourteen clinical trials and fifteen "real-world practice" studies.The average discontinuation rate was similar between clinical trials and "real-world practice" studies though the reasons for discontinuation differed. CLL progression was a more common reason for discontinuation in clinical trial studies while toxicity was a more common reason for discontinuation in "real-world practice" studies. Some studies have suggested worse outcomes in patients requiring dose reductions in ibrutinib while others have shown no change in treatment efficacy in patients requiring dose reductions due to concomitant CYP medications or increased immunosuppression post-transplant.The impact of ibrutinib dose modifications on clinical outcome remains unclear. Patients on concomitant CYP3A inhibitors should be prescribed a lower dose than the standard 420 mg daily, in order to maintain comparable pharmacologic properties. Further research is required to establish definitive clinical practice guidelines.
Annals Graphic Medicine - Intern Year
Authors: Mai Stewart
Journal: Annals of Internal Medicine (2020)

Web Exclusives16 June 2020Annals Graphic Medicine - Intern YearFREEMai Stewart, MDMai Stewart, MDUniversity of Maryland Medical Center, Baltimore, Maryland (M.S.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/G19-0080 SectionsAboutVisual AbstractPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Download figure Download PowerPoint Comments0 CommentsSign In to Submit A Comment Author, Article, and Disclosure InformationAffiliations: University of Maryland Medical Center, Baltimore, Maryland (M.S.)Disclosures: The author has disclosed no conflicts of interest. The form can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=G19-0080.Author/Illustrator Information: Mai Stewart, MD, is currently completing an internal medicine preliminary intern year before starting her radiology residency. You can find more of her illustrations at www.instagram.com/maidoodles.This article was published at Annals.org on 9 June 2020. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 16 June 2020Volume 172, Issue 12Page: W160-W161KeywordsConflicts of interestDiagnostic radiologyDisclosureHealth careResidency ePublished: 9 June 2020 Issue Published: 16 June 2020 Copyright & PermissionsCopyright © 2020 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Trans, gender diverse and non-binary adult experiences of social support: A systematic quantitative literature review
Authors: Eden Dowers, Carolynne White, Kay Cook, Jonathan Kingsley
Journal: International Journal of Transgender Health (2020)

Background: Trans, gender diverse and non-binary (TGDNB) adults experience significant health disparities relative to their cisgender peers. While social support is a known health-protective factor within the general population, no systematic reviews of TGDNB experiences of social support exist.Aim: To systematically review prior research of social support for TGDNB adults. We sought to assess the defining characteristics of the research, the participants and the research findings, mapping emerging trends across disciplines.Methods: Six electronic databases (PubMed, MEDLINE, CINAHL, Web of Science, LGBT Life and PsycNet) were searched for literature pertaining to TGDNB adults, social support, and health or well-being published in the past decade.Results: The findings illustrate a predominance of USA-based quantitative research that measures social support of friends, family and a singular intimate partner. The majority of participants were white, binary-identified transgender women and TGDNB people living in metropolitan settings. Social support was commonly reported as a protective factor, with TGDNB peer support the most frequently reported correlate of health and well-being for TGDNB adults.Discussion: The results suggest standardized inventories do not capture the emic nature of social support for TGDNB adults. A key opportunity lies in an inductive, hypothesis-forming approach to the study of what is socially supportive for TGDNB adults. In turn, this knowledge will enable the appropriate measurement, implementation and interpretation of social support studies.
Abstract B03: Acute megakaryoblastic leukemia is associated with poor overall survival and enriched in JAK2 variants
Authors: Marissa Li, Moritz Binder, Basma Basha, Ben Zhang, Alejandro Ferrer, Yuanhan Liu, Mrinal Patnaik, David Viswanatha, Naseema Gangat
Journal: Cancer Research (2020)

Abstract In this study, we aimed to characterize the molecular mechanisms of two very rare subtypes of AML: acute megakaryoblastic leukemia (AMKL) and acute panmyelosis with myelofibrosis (APMF). Our goal is to describe the clinical-pathologic features of APMF and explore the genomic landscape AMKL to further understand these rare malignancies. We identified 35 patients diagnosed with AMKL (n=27) and APMF (n=8) at Mayo Clinic between 1995 and 2015 by retrospective chart review. For 10 of the AMKL patients, tissue was available for whole-exome sequencing and was analyzed in comparison to a published AML reference population. The median overall survival was shorter in patients with AMKL (3.9 months, 95% CI 1.7-7.4) than in patients with APMF (14.3 months, 95% CI 0.7-NE, p = 0.026,). For both AMKL and APMF, patients who underwent allogeneic hematopoietic stem cell transplantation had better overall survival (14.3 months, 95% CI 1.9-NE) compared to those not undergoing transplantation (4.6 months, 95% CI 1.5-7.4, p = 0.003). Patients with AMKL presented more frequently with splenomegaly, with higher peripheral blood blast counts, and with higher serum lactate dehydrogenase concentrations. 9 out of 10 AMKL patients with available tissue for sequencing demonstrated variants in 22 of 35 AML driver genes, with JAK2 V617F as the most common mutation. Although our small study numbers preclude firm conclusions, it does reflect the rarity of these AML subtypes. Furthermore, inferior survival in AMKL (compared to APMF) was reflected in its proliferative disease features such as splenomegaly, high blast counts, and high lactate dehydrogenase. Interestingly, the presence of JAK2 V617F variants in 40% of the interrogated samples was higher than expected. Although JAK2 is a known molecular driver in myeloproliferative neoplasms, it is actually very rare in de novo AML (~1%). Despite improved survival with allogeneic stem cell transplant, we can conclude that treatment outcomes for AMKL and APMF with standard-of-care therapy were sobering and that patients with these rare AML subtypes should undergo molecular evaluation to qualify them for clinical trials with novel targeted therapies. Citation Format: Marissa Li, Moritz Binder, Basma Basha, Ben Zhang, Alejandro Ferrer, Yuanhan Liu, Mrinal Patnaik, David Viswanatha, Naseema Gangat. Acute megakaryoblastic leukemia is associated with poor overall survival and enriched in JAK2 variants [abstract]. In: Proceedings of the AACR Special Conference on the Evolving Landscape of Cancer Modeling; 2020 Mar 2-5; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2020;80(11 Suppl):Abstract nr B03.
Carfilzomib, lenalidomide, and dexamethasone (KRd) versus bortezomib, lenalidomide, and dexamethasone (VRd) for initial therapy of newly diagnosed multiple myeloma (NDMM): Results of ENDURANCE (E1A11) phase III trial.
Authors: Shaji Kumar, Susanna J. Jacobus, Adam D. Cohen, Matthias Weiss, Natalie Scott Callander, Avina A. Singh, Terri L. Parker, Alex R. Menter, Xuezhong Yang, Benjamin Marshall Parsons, Pankaj Kumar, Prashant Kapoor, Aaron Seth Rosenberg, Jeffrey A. Zonder, Edward Anthony Faber, Sagar Lonial, Paul G. Richardson, Robert Z. Orlowski, Lynne I. Wagner, S. Vincent Rajkumar
Journal: Journal of Clinical Oncology (2020)

LBA3 Background: Bortezomib (btz) combined with lenalidomide (len) and dexamethasone (dex) (VRd) is a standard initial therapy for NDMM. Carfilzomib (cfz), a next-generation proteasome inhibitor, in combination with len-dex (KRd) has shown higher efficacy in phase II trials. This randomized phase III trial was designed to examine if KRd improves progression free survival (PFS) compared to VRd in NDMM (current results), and whether indefinite maintenance with len improves OS compared with two-year maintenance (to be analyzed once data matures). Methods: Patients (Pts) with NDMM, were randomized to receive VRd or KRd in a 1:1 fashion for 36 weeks followed by a second randomization (1:1) to indefinite versus two years of len maintenance. Pts without del17p, t (14;16), t(14;20), plasma cell leukemia or high-risk GEP70 profile, were enrolled. VRd arm included btz 1.3 mg/m 2 on days(d) 1, 4, 8, and 11 (d 1, 8 for cycles 9-12), len 25 mg d 1-14, and dex 40 mg d 1, 2, 4, 5, 8, 9, 11, 12 of a 3-week (wk) cycle for 12 cycles, while pts in the KRd arm received cfz 36 mg/m 2 d 1, 2, 8, 9, 15, 16 with len 25 mg daily on d 1-21 and dex 40 mg wkly, in 4 wk cycles for 9 cycles. Maintenance included len 15mg d 1-21 every 4 wks. The study was designed to detect a hazard ratio (HR)=0.75 with 80% power at 1-sided 2.5% alpha and 399 PFS events (progression or death regardless of intervening therapy). Results: The study accrued 1087 pts (VRd=542, KRd=545). The median age was 65y. Treatment, efficacy, and toxicity data are in the table. At the second of 3 planned interim analyses, with PFS HR=1.04 (95% CI, 0.8 to 1.3, p=0.74), futility was met. Median PFS was VRd=34.4m and KRd=34.6m; no differences were seen based on age (&lt;65 or ≥65), presence or absence of t(4;14) or ISS stage. The three-year OS (95% CI) was similar: VRd 84% (80 to 88) and KRd 86% (82 to 89). Conclusions: In this randomized phase 3 trial, KRd did not improve PFS compared with VRd in NDMM. A significantly higher rate of cardio-pulmonary and renal toxicity was observed with KRd, while neuropathy rates were higher with VRd. VRd remains the standard triplet induction regimen in standard and intermediate risk NDMM, and a suitable backbone for 4 drug combinations. Clinical trial information: NCT01863550 . [Table: see text]
AB0478 CORONARY ATHEROSCLEROSIS IN BEHCET’S DISEASE
Authors: R. Goloeva, Z. Alekberova
Journal: Annals of the Rheumatic Diseases (2020)

Background: Behcet’s disease (BD) is systemic vasculitis, which affects all types and sizes of vessels. Increased carotid intima-media thickness (IMT) is parameter associated with subclinical atherosclerosis. Objectives: To determine the prevalence of atherosclerosis in pts with BD. Methods: 95 BD pts were evaluated and 45 healthy controls matched for age and gender. IMT was assessed by high-resolution B-mode ultrasonography. Serum concentration of high-sensitivity C-reactive protein (hs CRP) was measured by immunonephelometric assay (BN-100 Analyzer; Dade Behring). Lipid profile evaluation included total cholesterol, TGs, HDL, LDL and atherogenic index. Results: The male-to-female ratio was 3,7:1, the mean age of pts was 29.7 (23-35) yrs, the mean age at the disease onset - 19,9 (14-25) yrs, the mean disease duration - 9,6 (4-15) yrs. Conclusion: Coronary atherosclerosis in BD pts was lower than what we expected. The thinning IMT may be one of the risk factors for aneurysm formation in pts with BD. Disclosure of Interests: None declared
SARS-CoV-2-related paediatric inflammatory multisystem syndrome, an epidemiological study, France, 1 March to 17 May 2020
Authors: Alexandre Belot, Denise Antona, Sylvain Renolleau, Etienne Javouhey, Véronique Hentgen, François Angoulvant, Christophe Delacourt, Xavier Iriart, Caroline Ovaert, Brigitte Bader-Meunier, Isabelle Kone-Paut, Daniel Levy-Bruhl
Journal: Eurosurveillance (2020)

End of April 2020, French clinicians observed an increase in cases presenting with paediatric inflammatory multisystem syndrome (PIMS). Nationwide surveillance was set up and demonstrated temporospatial association with the coronavirus disease (COVID-19) epidemic for 156 reported cases as at 17 May: 108 were classified as confirmed (n = 79), probable (n = 16) or possible (n = 13) post-COVID-19 PIMS cases. A continuum of clinical features from Kawasaki-like disease to myocarditis was observed, requiring intensive care in 67% of cases.
Gut microbiota remodeling reverses aging-associated inflammation and dysregulation of systemic bile acid homeostasis in mice sex-specifically
Authors: Junli Ma, Ying Hong, Ningning Zheng, Guoxiang Xie, Yuanzhi Lyu, Yu Gu, Chuchu Xi, Linlin Chen, Gaosong Wu, Yue Li, Xin Tao, Jing Zhong, Zhenzhen Huang, Wenbin Wu, Lin Yuan, Min Lin, Xiong Lu, Weidong Zhang, Wei Jia, Lili Sheng, Houkai Li
Journal: Gut Microbes (2020)

Aging is usually characterized with inflammation and disordered bile acids (BAs) homeostasis, as well as gut dysbiosis. The pathophysiological changes during aging are also sexual specific. However, it remains unclear about the modulating process among gut microbiota, BA metabolism, and inflammation during aging. In this study, we established a direct link between gut microbiota and BA profile changes in the liver, serum, and four intestinal segments of both sexes during aging and gut microbiota remodeling by co-housing old mice with young ones. We found aging reduced Actinobacteria in male mice but increased Firmicutes in female mice. Among the top 10 altered genera with aging, 4 genera changed oppositely between male and female mice, and most of the changes were reversed by co-housing in both sexes. Gut microbiota remodeling by co-housing partly rescued the systemically dysregulated BA homeostasis induced by aging in a sex- and tissue-specific manner. Aging had greater impacts on hepatic BA profile in females, but intestinal BA profile in males. In addition, aging increased hepatic and colonic deoxycholic acid in male mice, but reduced them in females. Moreover, muricholic acids shifted markedly in the intestine, especially in old male mice, and partially reversed by co-housing. Notably, the ratios of primary to secondary BAs in the liver, serum, and all four intestinal segments were increased in old mice and reduced by co-housing in both sexes. Together, the presented data revealed that sex divergent changes of gut microbiota and BA profile in multiple body compartments during aging and gut microbiota remodeling, highlighting the sex-specific prevention and treatment of aging-related disorders by targeting gut microbiota-regulated BA metabolism should particularly be given more attention.
Abstract 11798: Cardiac Arrest Prevention Quality Improvement Project From the Pediatric Cardiac Critical Care Consortium
Authors: Jeffrey Alten, Darren Klugman, David S Cooper, Tia T Raymond, Sharyl Wooton, Katherine Clarke-Myers, Jeffrey B Anderson, Mousumi Banerjee, Sara K Pasquali, Michael G Gaies
Journal: Circulation (2019)

Introduction: Cardiac arrest (CA) rates vary substantially across pediatric cardiac ICUs (CICU), however it remains unknown whether CA prevention can be improved. The Pediatric Cardiac Critical Car...
Risk factors for disease progression in patients with mild to moderate coronavirus disease 2019—a multi-centre observational study
Authors: Y. Cen, X. Chen, Y. Shen, X.-H. Zhang, Y. Lei, C. Xu, W.-R. Jiang, H.-T. Xu, Y. Chen, J. Zhu, L.-L. Zhang, Y.-H. Liu
Journal: Clinical Microbiology and Infection (2020)
Practice Changes at U.S. Transplant Centers After the New Adult Heart Allocation Policy
Authors: William F. Parker, Kevin Chung, Allen S. Anderson, Mark Siegler, Elbert S. Huang, Matthew M. Churpek
Journal: Journal of the American College of Cardiology (2020)

In October 2018, the U.S. heart allocation system expanded the number of priority "status" tiers from 3 to 6 and added cardiogenic shock requirements for some heart transplant candidates listed with specific types of treatments. This study sought to determine the impact of the new policy on the treatment practices of transplant centers. Initial listing data on all adult heart candidates listed from December 1, 2017 to April 30, 2019 were collected from the Scientific Registry of Transplant Recipients. The status-qualifying treatments (or exception requests) and hemodynamic values at listing of a post-policy cohort (December 2018 to April 2019) were compared with a seasonally matched pre-policy cohort (December 2017 to April 2018). Candidates in the pre-policy cohort were reclassified into the new priority system statuses by using treatment, diagnosis, and hemodynamics. Comparing the post-policy cohort (N = 1,567) with the pre-policy cohort (N = 1,606), there were significant increases in listings with extracorporeal membrane oxygenation (+1.2%), intra-aortic balloon pumps (+ 4 %), and exceptions (+ 12%). Listings with low-dose inotropes (−18%) and high-dose inotropes (−3%) significantly decreased. The new priority status distribution had more status 2 (+14%) candidates than expected and fewer status 3 (−5%), status 4 (− 4%) and status 6 (−8%) candidates than expected (p values <0.01 for all comparisons). After implementation of the new heart allocation policy, transplant centers listed more candidates with extracorporeal membrane oxygenation, intra-aortic balloon pumps, and exception requests and fewer candidates with inotrope therapy than expected, thus leading to significantly more high-priority status listings than anticipated. If these early trends persist, the new allocation system may not function as intended.