tbuckley/cabot-search huggingface dataset:
INNV-02. ACCELERATING RESEARCH FOR BREAST CANCER BRAIN METASTASIS AND LEPTOMENINGEAL DISEASE THROUGH PATIENT-LED COLLABORATIONS
Authors: Christine Hodgdon
Journal: Neuro-Oncology (2021)

Abstract PATIENT-DRIVEN INITIATIVE OF THE METASTATIC BREAST CANCER (MBC) ALLIANCE The Breast Cancer Brain Metastasis (BCBM) Initiative: Marina Kaplan Project launched in June 2020 as an official project of the MBC Alliance which includes 32 nonprofits, 12 industry partners, and 30 individual patient advocates. The project has grown to include 35 members with representation from industry, research institutions, and individual patients. Nearly one-third of the group is comprised of patients living with brain metastases or LMD. DISPARITIES FOR PATIENTS LIVING WITH BCBM &amp; LMD In the US, approximately 200,000 new cases of brain metastases are diagnosed each year.1 Approximately 10-15% of patients with MBC will develop brain metastases, and may be as high as 30-50% for certain subtypes.2 A diagnosis of central nervous system (CNS) metastasis often accelerates an already incurable diagnosis. CNS metastasis are difficult to image and detect, tend to have poorer prognoses with lower overall survival, and are treated with invasive therapies which can have lasting side effects. Furthermore, most clinical trials exclude patients with CNS metastasis which further hinders research. VALUES &amp; OBJECTIVES The overarching goal of this initiative is to accelerate the scope and breadth of evidence-based CNS metastasis research by targeting entities conducting clinical trials and collaborating with them to do the following: (1) Increase the quality and quantity of basic research; (2) increase the number of clinical trials in areas where research is lacking; (3) diversify the type of clinical trial interventions; (4) eliminate restrictive eligibility criteria in clinical trials; (5) Incorporate clinically meaningful trial endpoints. References Eichler, April F et al. The biology of brain metastases-translation to new therapies. Nat Rev. Clinical oncology vol. 8,6 (2011): 344-56. doi: 10.1038/nrclinonc.2011.58 Brosnan EM, Anders CK. Understanding patterns of brain metastasis in breast cancer and designing rational therapeutic strategies. Ann Transl Med. 2018;6(9):163. doi: 10.21037/atm.2018.04.35
<i>Vital Signs:</i> HIV Infection, Diagnosis, Treatment, and Prevention Among Gay, Bisexual, and Other Men Who Have Sex with Men — United States, 2010–2019
Authors: Marc A. Pitasi, Linda Beer, Susan Cha, Shacara Johnson Lyons, Angela L. Hernandez, Joseph Prejean, Linda A. Valleroy, Stacy M. Crim, Lindsay Trujillo, Dominique Hardman, Elizabeth M. Painter, Jacqueline Petty, Jonathan H. Mermin, Demetre C. Daskalakis, H. Irene Hall
Journal: MMWR Morbidity and Mortality Weekly Report (2021)

Background.Men who have sex with men (MSM) accounted for two thirds of new HIV infections in the United States in 2019 despite representing approximately 2% of the adult population.Methods.CDC analyzed surveillance data to determine trends in estimated new HIV infections and to assess measures of undiagnosed infection and HIV prevention and treatment services including HIV testing, preexposure prophylaxis (PrEP) use, antiretroviral therapy (ART) adherence, and viral suppression, as well as HIV-related stigma.Results.The estimated number of new HIV infections among MSM was 25,100 in 2010 and 23,100 in 2019.New infections decreased significantly among White MSM but did not decrease among Black or African American (Black) MSM and Hispanic/Latino MSM.New infections increased among MSM aged 25-34 years.During 2019, approximately 83% of Black MSM and 80% of Hispanic/Latino MSM compared with 90% of White MSM with HIV had received an HIV diagnosis.The lowest percentage of diagnosed infection was among MSM aged 13-24 years (55%).Among MSM with a likely PrEP indication, discussions about PrEP with a provider and PrEP use were lower among Black MSM (47% and 27%, respectively) and Hispanic/Latino MSM (45% and 31%) than among White MSM (59% and 42%).Among MSM with an HIV diagnosis, adherence to ART and viral suppression were lower among Black MSM (48% and 62%, respectively) and Hispanic/Latino MSM (59% and 67%) compared with White MSM (64% and 74%).Experiences of HIV-related stigma among those with an HIV diagnosis were higher among Black MSM (median = 33; scale = 0-100) and Hispanic/Latino MSM (32) compared with White MSM (26).MSM aged 18-24 years had the lowest adherence to ART (45%) and the highest median stigma score (39). Conclusion.Improving access to and use of HIV services for MSM, especially Black MSM, Hispanic/Latino MSM, and younger MSM, and addressing social determinants of health, such as HIV-related stigma, that contribute to unequal outcomes will be essential to end the HIV epidemic in the United States.
Aiming for economic recovery from covid-19 and better climate resilience is a win-win
Authors: Alexander von Hildebrand
Journal: BMJ (2021)

I agree with Sherman and colleagues that “health professionals should encourage change through individual practice, influencing healthcare organisations, and contributing to standards and policy.”1

As an environmental health field worker for over 35 years in countries of the global south, I encountered too many healthcare facilities with no access to functional basic water, sanitation, and hygiene services. In these places, strategising for a net zero status is still far removed.

In 2015, the World Health …
When extended genetics rescues diagnosis: a patient with CANDLE-like phenotype and de novo mutation in the<i>SAMD9L</i>gene
Authors: Amandine Remy, Charlotte Borocco, Guillaume Sarrabay, Guilaine Boursier, Sylvie Fraitag, Benoit Catteau, Héloise Reumaux, Isabelle Koné-Paut
Journal: Annals of the Rheumatic Diseases (2021)

We read with interest Rusmini et al report1 that discussed the application of next-generation sequencing (NGS) in the diagnosis of systemic auto inflammatory diseases (SAID) in 2016. By developing an NGS panel of 10 SAID-associated genes on 50 patients with a known Sanger-identified variant, a third of them were found to carry one or more additional possible effective variants in at least one other gene. Nevertheless, their phenotypic contribution was doubtful, representing the most challenging issue for the use of NGS panels in the daily clinical practice. Herein, we report a striking illustration of the value of extended NGS in patients with unexpected phenotype. We describe the case of a child with prominent inflammatory and cutaneous phenotype, in whom the first NGS panel’s results hypothesised a diagnosis that is analogous to a chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature syndrome (CANDLE-like). Despite the identification of a single heterozygous variant in the PSMB8 gene, a second underlying pathogenic variant was suspected given that a genetic digenism is usually frequent in proteasome-associated auto-inflammatory syndromes. But there was more that met the eye: as the patient did not present typical features of CANDLE, genetic investigation was pursued with a whole-exome sequencing revealing a de novo frameshift mutation in the Sterile Alpha Motif Domain–containing protein 9-Like ( SAMD9L ) gene and leading to the diagnosis of SAMD9L-associated autoinflammatory disease (SAMD9L-SAAD).

The girl was born to unrelated …
Abstract 14285: Plasma Proteomic Profiling of Endurance Exercise Identifies Changes in Extracellular Matrix Biology Associated With Adaptations in Maximal Oxygen Uptake
Authors: Jeremy Robbins, Prashant Rao, Michael Mi, Michelle Keyes, Shuliang Deng, Daniel H Katz, Pierre M Jean Beltran, Usman A Tahir, Jacob Barber, Laurie Farrell, Clary Clish, Mark A Sarzynski, Claude Bouchard, Robert E Gerszten
Journal: Circulation (2021)

Introduction: Proteins are important regulators of cardiometabolic health that are increasingly recognized as being modulated by exercise. Hypothesis: We measured approximately 5,000 plasma proteins before and after an endurance exercise training (ET) program to test the hypothesis that proteomic changes are related to adaptations in maximal oxygen uptake ( Δ VO2max) and long-term health outcomes. Methods: We applied an affinity-based proteomics platform before and after ET in 654 sedentary participants (mean age = 35, 35% black) from the HERITAGE Study. Subjects performed graded cycle ergometry, exercising at 75% VO2max, 3x/week over the final 6 weeks of a 20-week program. Changes in plasma protein levels after ET were determined using paired t tests. Multivariate linear regression assessed the relationship between Δ protein and Δ VO2max after ET. Statistical significance was determined using a false discovery rate (FDR) &lt; 0.05. Multivariate cox proportional hazards regression estimated hazard ratios (HR) of protein levels and all-cause mortality in the Framingham Heart Study (FHS) and Malmo Diet and Cancer Study (MDCS). Results: 455 proteins changed after ET, including 306 proteins that increased. Proteins related to the extracellular matrix (ECM) were overrepresented among biologic processes and pathways in enrichment analyses. Absolute changes in five proteins after ET were related to ΔVO2max [FTH1: (β = -31.8, q = 0.009), CDH5 (β = 28.3, q = 0.028), FAP (β = 28.0, q = 0.025), ANGPT2 (β = 28.1, q = 0.028), PRELP (β = 26.6, q = 0.044) after adjustment for age, sex, race, BMI, and baseline VO2max. Fibroblast activation protein (FAP), was positively associated with baseline VO2max (β = 43.6, p = 0.02) and inversely related to all-cause mortality in FHS and MDCS (HR = 0.84 and 0.86, p = 0.0002 and 0.004, respectively). Conclusions: Endurance exercise leads to large-scale plasma proteomic changes, including increased levels of ECM-related proteins. Several novel proteins modulated by ET were associated with Δ VO2max, including FAP, a serine protease relevant in wound healing and metabolism that is inversely associated with mortality in two separate cohorts. External validation and additional efforts to understand FAP’s mechanistic relevance are warranted.
Abstract 10781: Improving Medication Communication Following Percutaneous Coronary Intervention
Authors: Keri Q Kohlmann, Michael T Ring, Angela L Fink
Journal: Circulation (2021)

Introduction: Patients undergoing percutaneous coronary intervention (PCI) acquire or continue an average of five medications specific to their intervention during hospitalization, some of which are continued for life. It has been identified that poor communication between health care professionals and patients is a contributor to medication nonadherence. The aim of this quality improvement project was to determine if the implementation of individualized medication education forms and patient-centered medication training would improve nurse-patient medication communication. Methods: Project interventions were implemented on a post-PCI telemetry unit from December 2020 to February 2021. Patients with acute coronary syndrome requiring PCI during hospitalization were surveyed on five domains at the time of discharge from October 2020 to February 2021. The five domains included: 1) medication communication 2) confidence in medication name recall 3) ability to manage medications 4) understanding of medication purposes and 5) side effect management. Results: A total of 53 patients were included in this analysis, with 28 in the pre-intervention group and 25 in the post-intervention group. Comparatively, patients in the post-intervention group reported a subjective improvement in medication communication, confidence in recalling medication names, ability to manage medications, and understanding of medication purposes and side effects when compared to patients in the pre-intervention group. Conclusion: The use of multidimensional, standardized medication education forms and medication training positively impacted medication communication between nursing and post-PCI patients.
CTNI-21. PHASE 2 STUDY OF VAL-083 AND RADIOTHERAPY IN NEWLY DIAGNOSED MGMT-UNMETHYLATED GBM
Authors: Zhong-ping Chen, Cheng-Cheng Guo, Yang Qun-ying, Jia-Wei Li, Shao-xiong Wu, Jeffrey Bacha, Gregory Johnson, John Langlands, Claire Kwan, Sarath Kanekal, Richard Schwartz, Anne Steino, Dennis Brown
Journal: Neuro-Oncology (2021)

Abstract Approximately 60% of glioblastoma multiforme (GBM) patients possess an unmethylated methylguanine DNA-methyltransferase (MGMT) gene promoter, which confers a limited clinical response to standard-of-care treatment with temozolomide (TMZ), resulting in shorter median survival when compared to patients with a methylated MGMT promoter. VAL-083 is a novel bi-functional DNA targeting agent that induces interstrand DNA cross-links at N7-guanine, leading to DNA double-strand breaks and ultimately cell death. VAL-083 circumvents MGMT-mediated TMZ resistance in vitro and in vivo. A Phase 2 study has been conducted to evaluate efficacy and safety of VAL-083 when administered concurrently with radiation therapy (RT) in newly diagnosed MGMT unmethylated GBM. The study was conducted in 2 stages: Stage 1 was a dose-escalation phase to confirm the dose of VAL-083 in this setting. Patients received VAL-083 at 20, 30, or 40 mg/m2/day x 3 days every 21 days along with standard radiation treatment (RT) (2 Gy/day, 5 days/week for 6 weeks). At the end of this stage, 30 mg/m2/day of VAL-083 in combination with RT was generally safe and well-tolerated. Stage 2 was an expansion phase to enroll up to 20 additional patients at the 30 mg/m2/day of VAL-083 in combination with RT. All patients have been enrolled, with a total of 29 patients in the study, and 25 patients receiving 30 mg/m2/day VAL-083. All 29 patients have completed treatment and patients are in the follow-up phase of the study. Consistent with our prior experience, myelosuppression was the most common adverse event. As of March 2021, 22/29 (75.9%) subjects had disease progression. The median progression free survival for all patients enrolled was 9.3 (95%CI: 6.4-12.0) months. Sixteen (16/29; 55.2%) patients had died, and median overall survival for all patients enrolled was 19.6 (95%CI: 14.0-22.4) months. Further safety and efficacy updates will be presented at the meeting. Clinicaltrials.gov identifier: NCT03050736.
Long-Term Outcomes of Patients with Large B-Cell Lymphoma Treated with Standard-of-Care Axicabtagene Ciloleucel: Results from the US Lymphoma CAR-T Cell Consortium
Authors: Jay Y. Spiegel, Michael D. Jain, Loretta Nastoupil, John Tamaresis, Armin Ghobadi, Yi Lin, Lazaros J. Lekakis, Patrick M. Reagan, Olalekan O. Oluwole, Joseph P. McGuirk, Abhinav Deol, Alison R. Sehgal, Andre H. Goy, Brian T. Hill, Charalambos Andreadis, Javier Muñoz, Matthew L. Ulrickson, Jason R. Westin, Julio C. Chavez, Miriam T. Jacobs, N Nora Bennani, Aaron P. Rapoport, Julie M. Vose, David B. Miklos, Sattva S. Neelapu, Frederick L. Locke, Saurabh Dahiya, Matthew A. Lunning
Journal: Blood (2021)
Alzheimer’s disease and progressive supranuclear palsy share similar transcriptomic changes in distinct brain regions
Authors: Xue Wang, Mariet Allen, Özkan İş, Joseph S. Reddy, Frederick Q. Tutor-New, Monica Castanedes Casey, Minerva M. Carrasquillo, Stephanie R. Oatman, Yuhao Min, Yan W. Asmann, Cory Funk, Thuy Nguyen, Charlotte C.G. Ho, Kimberly G. Malphrus, Nicholas T. Seyfried, Allan I. Levey, Steven G. Younkin, Melissa E. Murray, Dennis W. Dickson, Nathan D. Price, Todd E. Golde, Nilüfer Ertekin-Taner
Journal: Journal of Clinical Investigation (2021)

Vast numbers of differentially expressed genes and perturbed networks have been identified in Alzheimer's disease (AD), however, neither disease nor brain region specificity of these transcriptome alterations has been explored. Using RNA-Seq data from 231 temporal cortex and 224 cerebellum samples from patients with AD and progressive supranuclear palsy (PSP), a tauopathy, we identified a striking correlation in the directionality and magnitude of gene expression changes between these 2 neurodegenerative proteinopathies. Further, the transcriptomic changes in AD and PSP brains ware highly conserved between the temporal and cerebellar cortices, indicating that highly similar transcriptional changes occur in pathologically affected and grossly less affected, albeit functionally connected, areas of the brain. Shared up- or downregulated genes in AD and PSP are enriched in biological pathways. Many of these genes also have concordant protein changes and evidence of epigenetic control. These conserved transcriptomic alterations of 2 distinct proteinopathies in brain regions with and without significant gross neuropathology have broad implications. AD and other neurodegenerative diseases are likely characterized by common disease or compensatory pathways with widespread perturbations in the whole brain. These findings can be leveraged to develop multifaceted therapies and biomarkers that address these common, complex, and ubiquitous molecular alterations in neurodegenerative diseases.
Abstract 9672: Antiplatelet Therapy and Covid-19 Outcomes in Patients With Stable Coronary Artery Disease
Authors: Andrew Adelsheimer, Justin Choi, Arthur Evans
Journal: Circulation (2021)

Introduction: Severe COVID-19 can cause acute respiratory distress syndrome (ARDS), with pulmonary pathology composed of platelet microthrombi. Antiplatelet agents have been investigated as a treatment in ARDS, but without clear evidence of benefit. The decision on antiplatelet use in patients with COVID-19 and coronary artery disease (CAD) is key. Hypothesis: We assessed the hypothesis that increased use of antiplatelet therapy was associated with no worse clinical outcomes in COVID-19 among adults with stable CAD. Methods: We performed a retrospective cohort study of patients who presented with COVID-19 to two New York City hospitals from March 3 to May 15, 2020. Patients were separated into groups based on antiplatelet use, including no outpatient antiplatelet use, monotherapy, and dual antiplatelet therapy (DAPT). Outcomes and complications were compared among the groups, using propensity scoring with inverse probability of treatment weighting. Results: This study included 315 patients with stable CAD and COVID-19. Patients on no outpatient antiplatelet therapy were significantly older and more likely to be taking anticoagulation, while patients on DAPT had the highest rates of diabetes and chronic kidney disease. The most prescribed antiplatelet in the cohort was aspirin (72.1%) followed by clopidogrel (22.5%). There was no difference in COVID-19 admission mortality between the DAPT and monotherapy groups (DAPT 27.9%, monotherapy 27.2%, p=NS). Patients on DAPT had decreased rates of venous thromboembolism compared to monotherapy (DAPT 0.0%, monotherapy 6.4%, p=0.01), and bleeding rates were similar. The rate of home monotherapy continuation in hospital was 79.9%, with the most common reasons for discontinuation being hemorrhage, anemia, and thrombocytopenia. No outpatient antiplatelet use was a high-risk group, with the highest rates of intensive care admissions, intubations and mortality. Conclusions: In conclusion, we found no difference in COVID-19 outcomes for CAD patients on DAPT compared to those on monotherapy. There were decreased clotting complications in patients on more antiplatelet therapy, while bleeding rates were similar. No outpatient antiplatelet use was found to be a high-risk group in COVID-19.
Importance of the pig as a human biomedical model
Authors: Joan K. Lunney, Angelica Van Goor, Kristen E. Walker, Taylor Hailstock, Jasmine Franklin, Chaohui Dai
Journal: Science Translational Medicine (2021)

Pigs have substantial potential as biomedical models for studying human developmental processes, congenital diseases, and pathogen response mechanisms in addition to utility as xenotransplant organ donors and tools for vaccine and drug design. The similarity of pigs to humans in anatomical size and structure, physiology, immunology, and genome enhances their potential as models for humans. Hence, it is imperative that research is relevant and reproducible in animal models that more closely resemble humans, such as the pig. This review summarizes the current status of pigs as an investigative model for humans and highlights their future applications.
Single-Agent Ibrutinib Versus Real-World (RW) Treatments for Patients with Previously Untreated Chronic Lymphocytic Leukemia (CLL): Adjusted Comparison of Resonate-2™ with the Cllear and Lyon-Sud Rw Databases
Authors: Michael Doubek, Mudr. Lukas Smolej, Martin Šimkovič, Anna Panovska, Renata Urbanova, Daniel Lysak, Evelyne Callet-Bauchu, Emmanuel Bachy, Lucile Baseggio, Emmanuelle Ferrant, Joris Diels, Jedelyn Cabrieto, Lasse Nielsen, Gilles Salles
Journal: Blood (2021)
Abstract 10654: Prevalence and Outcomes of Patients with HFrEF and Alzheimer's Disease and Related Dementias (ADRD)
Authors: Lauren Gilstrap, Gregory Ouellet, Andrew Cohen, Danette Flint, Barbara Gladders, Andrea Austin, Jonathan Skinner
Journal: Circulation (2021)

Introduction: The average Medicare beneficiary with HFrEF is now 80 years old. Alzheimer’s Disease and Related Dementias (ADRD) is more common among older adults. Yet, to date the rate of ADRD in HFrEF has not been well studied. This is important because the treatment of HFrEF relies on a complex medication regimen and often-challenging lifestyle modifications, things that are particularly difficult in the setting of concurrent cognitive impairment. The aim of this study is to determine the prevalence and outcomes of patients with concurrent HFrEF and ADRD (HF+ADRD). Methods: We used 100% Medicare Parts A and B and a random 40% sample of Part D to create a cohort of 397,680 fee-for-service beneficiaries with ≥1 hospitalization for HFrEF between 2012 and 2018. We required 1 year of FFS before and after discharge to capture comorbidities and measure outcomes over time. We used previously validated ICD-9/10 codes to define ADRD. Results: Thirteen percent (n=53,092) of patients with HFrEF have concurrent ADRD. The average patient with HF+ADRD is 4 years older than the average non-ADRD HF patient and rates of hypertension, diabetes, renal failure, lung disease, vascular disease and frailty are all higher among HF+ADRD patients (p&lt;0.001; Table 1 ). Differences in 30-day and 1-year readmission rates are statistically significant, but relatively small. (30-day: 23% vs. 25%; 1-year: 64% vs. 66% ,p&lt;0.001). However, 30-day and 1-year mortality rates are markedly higher for HF+ADRD patients (30-day: 5% vs. 10%; 1-year: 30% vs. 49%). Conclusions: Thirteen percent of HFrEF patients have concurrent ADRD. On average, this population is older, frailer and has more comorbidities than HFrEF patients without ADRD. While readmission rates are similar, HF+ADRD patients have markedly higher short and long-term mortality. Additional work is needed to understand how much of this increased mortality can be prevented with improved HFrEF care.