tbuckley/cabot-search huggingface dataset:
Abstract 10507: Pyridoxamine Protects Against Cardiotoxicity After Doxorubicin Chemotherapy
Authors: Sibren Haesen, Aline Brillouet, Iris de Laat, Lotte Vastmans, Lize Evens, Sarah D'Haese, Esther Wolfs, Dorien Deluyker, Virginie Bito
Journal: Circulation (2021)

Introduction: Although doxorubicin (DOX) is an efficient anthracycline agent used to treat cancer, it induces cardiotoxicity and mortality in cancer survivors. Cardioprotection is inadequate. The vitamin B 6 -derivative pyridoxamine (PM) has shown to be cardioprotective in diverse cardiac diseases. Whether PM offers cardioprotection after DOX treatment is unknown. We hypothesized that PM limits cardiac impairment after DOX treatment by reducing cardiac fibrosis and inflammation. Methods: Female Sprague Dawley rats were weekly treated with 2 mg/kg DOX or saline IV for 8 weeks. At DOX treatment onset, 2 extra groups received PM (1 g/L) via the drinking water. Echocardiographic (4D) and hemodynamic parameters were assessed at week 8, together with plasma BNP. PCR analysis was performed on left ventricular tissue to evaluate fibrosis and inflammation. Data were compared using 1-way ANOVA, Kruskal-Wallis test or 2-way ANOVA with post-hoc tests as appropriate. Results: As shown in Table 1, cardiac impairment by DOX was prevented by PM. In addition, DOX significantly increased the expression of fibrosis markers, such as TGFβ (0.29 ± 0.02 vs. 0.69 ± 0.09 a.u., p&lt;0.0001), LOX (0.055 ± 0.002 vs. 0.590 ± 0.174 a.u., p&lt;0.01), collagen type 1 (0.21 ± 0.02 vs. 0.62 ± 0.11 a.u., p&lt;0.001) and interstitial collagen (4.6 ± 0.3 vs. 7.7 ± 0.6%, p&lt;0.001). DOX also increased the inflammation marker IL-6 (0.13 ± 0.03 vs. 0.73 ± 0.13 a.u., p&lt;0.01). PM treatment significantly lowered all these parameters (p&lt;0001, p&lt;0.001, p&lt;0.01, p&lt;0.01 and p&lt;0.01 respectively). Conclusions: In conclusion, our data show that DOX causes dilated cardiomyopathy with reduced ejection fraction, accompanied by cardiac fibrosis and myocarditis. As PM limits this adverse phenotype, it could be a novel cardioprotective strategy for DOX-treated cancer patients.
Abstract P029: MOBILE Intervention In College Students With Elevated Blood Pressure: A Pilot Study
Authors: Dieu-My T Tran, Iris Martinez, Chad Cross, Yumei Feng Earley
Journal: Circulation (2022)

Background and Purpose: Hypertension is a known risk factor that accelerates and leads to cardiovascular disease. While it is often a risk factor recognized in middle-aged and older adults, it is overlooked in young adults. The purpose of this study was to (1) implement a mHealth intervention, the O ptimize B lood Pressure I mprovement ( MOBI LE) intervention, in college students, aged 18 to 29 years, with elevated blood pressure (BP); and (2) test its feasibility and impact on BP reduction (primary outcome) along with sodium intake and hypertension knowledge improvement (secondary outcomes) after 28 days. Methods: The pilot study used a two-arm, randomized controlled trial. Subjects in the intervention group were required to monitor their daily BP. We recruited full-time students who had regular access to a mobile smartphone with unlimited texting and elevated BP or undiagnosed hypertension stage I. We excluded students who were pregnant, lactating, planning to become pregnant during the study, taking antihypertensive medication, or diagnosed with a life-threatening illness or condition associated with hypertension. We conducted the formative phase before the intervention phase to assess the acceptability, engagement, and feasibility of the intervention motivational text messages. During the educational session for baseline data, all subjects completed a sociodemographic questionnaire, the Automated Self-Administered 24-Hour Dietary Assessment Tool (ASA24), and the Hypertension Knowledge-Level Scale. Following, all subjects’ height and weight were also collected to calculate body mass index. For 28 days, subjects in the intervention group provided their daily BP measurement using the Withings wireless BP cuff and their motivational levels (1 for low motivation, 3 for moderate motivation, and 5 for high motivation) to receive the appropriate text message. After 28 days, all subjects were scheduled for an exit interview to collect post intervention data along with an exit interview. The control group completed the educational session and exit interview only. Results: Twenty-nine participants (intervention: n = 15; control: n = 14) completed the study. We found a significant decrease in BP in the intervention group ( p = 0.001) while no statistical significance was found in the control group. Using the ASA24 to extract sodium intake, there was no statistical difference in sodium intake for intervention or control groups. The mean hypertension knowledge score increased in both groups after 28 days; however, the improvement was only significant for the control group ( p = 0.001). Conclusions: The results provided preliminary data on the effect of BP reduction in both groups with more impact on the intervention group. These promising findings warrant further examination of the intervention and its long-term effects.
Real-World Evidence in Support of Oncology Product Registration: A Systematic Review of New Drug Application and Biologics License Application Approvals from 2015–2020
Authors: Bhakti Arondekar, Mei Sheng Duh, Rachel H. Bhak, Maral DerSarkissian, Lynn Huynh, Kelsey Wang, John Wojciehowski, Melody Wu, Bryon Wornson, Alexander Niyazov, George D. Demetri
Journal: Clinical Cancer Research (2021)

Abstract Real-world evidence (RWE) has garnered great interest to support registration of new therapies and label expansions by the United States Food and Drug Administration (FDA). Currently, practical insights on the design and analysis of regulatory-grade RWE are lacking. This study aimed to analyze attributes of real-world studies in FDA's decision-making and characteristics of full versus accelerated approvals through a systematic review of oncology product approvals. Oncology approvals from 2015 to 2020 were reviewed from FDA.gov. Applications were screened for inclusion of RWE, and variables related to regulatory designations of the application, pivotal clinical trial, and real-world studies were extracted. FDA feedback was reviewed to identify takeaways and best practices for adequate RWE. Among 133 original and 573 supplemental approvals for oncology, 11 and 2, respectively, included RWE; none predated 2017. All real-world studies were retrospective in nature; the most common data source was chart review, and the most common primary endpoint was overall response rate, as in the pivotal trial. The FDA critiqued the lack of the following: a prespecified study protocol, inclusion/exclusion criteria matching to the trial, comparability of endpoint definitions, methods to minimize confounding and address unmeasured confounding, and plans to handle missing data. All full (versus accelerated) approvals shared the following characteristics: high magnitude of efficacy in the pivotal trial; designations of orphan disease, breakthrough therapy, and priority review; and no advisory committee meeting held. This study found that findings from external control real-world studies complemented efficacy data from single-arm trials in successful oncology product approvals.
Abstract EP52: Using Human-Centered Design Methodology To Identify Challenges In Cardiac Recovery And Cardiac Rehabilitation From Diverse Patient, Patient Health Partner, And Clinician Perspectives
Authors: Zane T MacFarlane, Nino Isakadze, Nancy Molello, Erin Spaulding, Yumin Gao, Lisa Young, Shireen Khoury, Erin Michos, Oscar H Cingolani, Angela Street, Lena Mathews, Francoise A Marvel, Yvonne Commodore-Mensah, Seth S Martin
Journal: Circulation (2022)

Introduction: Despite overwhelming evidence for improved patient outcomes with Cardiac Rehabilitation (CR) after a cardiovascular event, CR participation remains markedly low, especially for women and those from underrepresented racial/ethnic groups. Objective: To identify challenges encountered during cardiac recovery and CR by engaging key stakeholders in human-centered design (HCD) sessions to guide development of solutions to increase CR participation. Methods: HCD is a methodology that is used to solve complex problems with the engagement of end-users. We recruited a) patients who were eligible for CR and deemed low to moderate risk for exercise, b) patient health partners, and c) clinicians with experience providing care to cardiovascular patients. We conducted separate meetings for patient/patient health partner and clinician groups virtually via Zoom to identify challenges, motivators, and themes for these groups in the setting of cardiac recovery and CR participation. Sessions were conducted using a semi-structured interview guide based on HCD methodology to identify emerging themes. Results: There were 11 patients, 4 patient health partners, and 10 clinicians enrolled in the study. Demographics and broad themes identified during virtual HCD sessions summarizing challenges shared by key stakeholders are reported in Figure 1. Conclusions: HCD sessions engaging a diverse group of patients, patient health partners, and clinicians identified challenges in the setting of cardiac recovery and CR and highlighted similar concepts among different stakeholders. We aim to conduct future sessions to further co-design a digital health intervention for virtual delivery of CR addressing these challenges. Figure 1. Demographics and top themes from virtual HCD sessions summarizing challenges during cardiac recovery and CR. CR = cardiac rehabilitation, CABG = coronary artery bypass graft surgery, IQR = interquartile range, MI = myocardial infarction.
Severe Thrombocytopenia in Patients With Advanced Neuroendocrine Tumor Treated With Peptide Receptor Radioligand Therapy
Authors: Junid A. Naveed Ahmad, Brett B. Schroeder, Steven M. Ruhoy, Hagen F. Kennecke, Bruce S. Lin
Journal: Clinical Nuclear Medicine (2022)

Background Peptide receptor radioligand therapy (PRRT) was Food and Drug Administration approved in 2018 for the treatment of unresectable somatostatin receptor–positive gastroenteropancreatic neuroendocrine tumors (NETs) and provides an important option for patients with advanced disease. A known adverse effect of this treatment is hematologic toxicity, although usually transient. We present 3 patients with metastatic gastroenteropancreatic NETs treated with PRRT who were evaluated for severe persistent thrombocytopenia. Methods Three patients who commenced therapy with PRRT were known to proceed to a bone marrow (BM) biopsy for persistent severe thrombocytopenia and were included in this study. These patients were identified retrospectively and evaluated for their tumor properties, including immunohistochemical markers, treatment modalities, and clinical outcomes. Results All 3 patients had metastatic NETs that progressed on prior lines of therapy and were treated with 1 to 4 doses of 177 Lu-DOTATATE 7.4 GBq (200 mCi) before developing grade 3 (25,000 to 50,000/μL) refractory thrombocytopenia. All patients had concurrent bone metastases, and 2 of the 3 had baseline grade 1 thrombocytopenia. In all 3 cases, BM biopsy documented widespread tumor infiltration. Conclusions Severe refractory thrombocytopenia after PRRT is rare and may result from numerous known causes, including radiation-induced myelotoxicity, myelodysplastic syndrome, and tumor BM infiltration. We present 3 cases of thrombocytopenia related to persistent or progressive BM metastasis. Although known bone metastasis is not a contraindication to PRRT, thrombocytopenia may be a manifestation of tumor progression and should be considered when making decisions about continuation of therapy.
Abstract P037: Age Modifies The Inverse Association Between Standing Height And Pulse Pressure
Authors: Aayush Visaria, Fariha Hameed, Devam Patel, Cole Jenkins, Purva Khanapure, David Lo
Journal: Circulation (2022)

Purpose: While standing height is positively associated with blood pressure in the pediatric population, studies have suggested an inverse association in adults. We sought to therefore determine whether age modified the association between standing height and pulse pressure (PP). Methods: The study included adults ≥20 years from the 1999-2018 National Health and Nutrition Examination Surveys who were not taking antihypertensive medications. Standing height was categorized into gender-specific quintiles (Table). High PP was defined as PP ≥60 mmHg. We estimated odds ratios (OR) using logistic regression, adjusting for covariates, accounting for the complex survey design, and stratifying by 10-year age groups. Results: Among the 26,779 adults (mean [SD] age of 43 [30], 50% female, 70% White), 16% had elevated PP, ranging from 23% in the lowest height quintile (Q1) to 11% in the highest quintile (Q5). Those in Q5 were younger, of higher socioeconomic status, had greater waist circumference, and less likely to have cardiovascular disease or diabetes compared to those in Q1. Those in Q5 had 46% lower adjusted odds of high PP compared to Q1. Race and gender did not modify associations (race: p for interaction = 0.28; gender: p =0.34). When stratifying by 10-year age groups, odds of high PP significantly decreased with increasing age up to 70 years (Table, P-trend &lt;0.001). Conclusion: Standing height was found to be negatively associated high PP, especially in adults 30-69 years. We speculate that augmented pulse wave deflection in shorter individuals may play a role in age-related increases in arterial stiffness.
New Creatinine- and Cystatin C–Based Equations to Estimate GFR without Race
Authors: Lesley A. Inker, Nwamaka D. Eneanya, Josef Coresh, Hocine Tighiouart, Dan Wang, Yingying Sang, Deidra C. Crews, Alessandro Doria, Michelle M. Estrella, Marc Froissart, Morgan E. Grams, Tom Greene, Anders Grubb, Vilmundur Gudnason, Orlando M. Gutiérrez, Roberto Kalil, Amy B. Karger, Michael Mauer, Gerjan Navis, Robert G. Nelson, Emilio D. Poggio, Roger Rodby, Peter Rossing, Andrew D. Rule, Elizabeth Selvin, Jesse C. Seegmiller, Michael G. Shlipak, Vicente E. Torres, Wei Yang, Shoshana H. Ballew, Sara J. Couture, Neil R. Powe, Andrew S. Levey
Journal: New England Journal of Medicine (2021)

Current equations for estimated glomerular filtration rate (eGFR) that use serum creatinine or cystatin C incorporate age, sex, and race to estimate measured GFR. However, race in eGFR equations is a social and not a biologic construct.
Decision Making in Geriatric Oncology: Supported Versus Assisted Decision Making
Authors: Sabine Sommerlatte, Heike Schmidt, Dirk Vordermark, Jan Schildmann
Journal: Journal of Clinical Oncology (2021)

DuMontier et al 1 have performed a comprehensive overview on a broad range of medical, ethical, and legal aspects to be considered regarding decision making connected with older patients with cancer.We would like to add two points which seem relevant from our clinical experience and an ethical perspective to further improve decision making with older adults.
Correction to: Aortic Valve Replacement Versus Conservative Treatment in Asymptomatic Severe Aortic Stenosis: The AVATAR Trial
Journal: Circulation (2022)

a correction is needed.In Table 3, the KM 3-year rate results for HF and all-cause death were mistakenly switched, so that estimated event rates for all-cause death are in HF line, and estimated event rates for HF are in the all-cause death line.That has been corrected.The given hazard ratio and 95% confidence interval have stayed the same.
Abstract P025: Cigarette Smoking And Risk Of Hospitalization With Acute Kidney Injury: The Atherosclerosis Risk In Communities (aric) Study
Authors: Mengkun Chen, Ning Ding, Morgan Grams, Kuni Matsushita, Junichi Ishigami
Journal: Circulation (2022)

Title: Cigarette smoking and risk of hospitalization with acute kidney injury: The Atherosclerosis Risk in Communities (ARIC) Study Background: Smoking has been associated with progression of chronic kidney disease. However, its association with the development of acute kidney injury (AKI) has not been prospectively assessed in the community. AKI poses significant morbidities and healthcare costs, thus understanding modifiable risk factors of AKI is crucial. Methods: Among 14,587 participants (mean age 54 [standard deviation: 6] years, 55% females and 25.4% Blacks) from the Atherosclerosis Risk in Communities Study, we quantified the association of smoking status with incident hospitalization with AKI (AKI diagnosis on discharge records in any diagnostic position) through 2019 using Cox models. Sensitivity analyses included censoring interim CVD events during follow-up and restricting to AKI as the primary diagnosis. Results: Over a median follow-up of 26.3 years, 2,986 participants had incident hospitalization with AKI (incidence rate per 1,000 person-years: 8.8; 95% CI: 8.4-9.1). In multivariable Cox models, current smokers had a &gt;2-fold higher risk of AKI compared with never smokers (HR: 2.25; 95% CI: 2.04-2.48) (Table). There was a dose-response relationship between smoking pack-years at baseline and risk of AKI (e.g., HRs 1.34 [1.21, 1.50] with 10-25 pack-years, 1.78 [1.59, 1.99] with 25-40 pack-years, and 2.03 [1.80-2.29] with ≥40 pack-years vs. never smokers). These associations were consistent with similar HRs in the two sensitivity analyses censoring interim cardiovascular diseases and analyzing AKI as the primary cause of hospitalization (Table). Conclusions: In a community-based cohort, smoking was associated with the risk of incident hospitalization with AKI, which was independent of potential confounders and robust in a few sensitivity analyses. These results suggest the importance of smoking cessation to reduce the risk of AKI.
Risk factors and disease profile of post-vaccination SARS-CoV-2 infection in UK users of the COVID Symptom Study app: a prospective, community-based, nested, case-control study
Authors: Michela Antonelli, Rose S Penfold, Jordi Merino, Carole H Sudre, Erika Molteni, Sarah Berry, Liane S Canas, Mark S Graham, Kerstin Klaser, Marc Modat, Benjamin Murray, Eric Kerfoot, Liyuan Chen, Jie Deng, Marc F Österdahl, Nathan J Cheetham, David A Drew, Long H Nguyen, Joan Capdevila Pujol, Christina Hu, Somesh Selvachandran, Lorenzo Polidori, Anna May, Jonathan Wolf, Andrew T Chan, Alexander Hammers, Emma L Duncan, Tim D Spector, Sebastien Ourselin, Claire J Steves
Journal: The Lancet Infectious Diseases (2021)

COVID-19 vaccines show excellent efficacy in clinical trials and effectiveness in real-world data, but some people still become infected with SARS-CoV-2 after vaccination. This study aimed to identify risk factors for post-vaccination SARS-CoV-2 infection and describe the characteristics of post-vaccination illness.
Protection by a Fourth Dose of BNT162b2 against Omicron in Israel
Authors: Yinon M. Bar-On, Yair Goldberg, Micha Mandel, Omri Bodenheimer, Ofra Amir, Laurence Freedman, Sharon Alroy-Preis, Nachman Ash, Amit Huppert, Ron Milo
Journal: New England Journal of Medicine (2022)

On January 2, 2022, Israel began administering a fourth dose of BNT162b2 vaccine to persons 60 years of age or older. Data are needed regarding the effect of the fourth dose on rates of confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and of severe coronavirus disease 2019 (Covid-19).Using the Israeli Ministry of Health database, we extracted data on 1,252,331 persons who were 60 years of age or older and eligible for the fourth dose during a period in which the B.1.1.529 (omicron) variant of SARS-CoV-2 was predominant (January 10 through March 2, 2022). We estimated the rate of confirmed infection and severe Covid-19 as a function of time starting at 8 days after receipt of a fourth dose (four-dose groups) as compared with that among persons who had received only three doses (three-dose group) and among persons who had received a fourth dose 3 to 7 days earlier (internal control group). For the estimation of rates, we used quasi-Poisson regression with adjustment for age, sex, demographic group, and calendar day.The number of cases of severe Covid-19 per 100,000 person-days (unadjusted rate) was 1.5 in the aggregated four-dose groups, 3.9 in the three-dose group, and 4.2 in the internal control group. In the quasi-Poisson analysis, the adjusted rate of severe Covid-19 in the fourth week after receipt of the fourth dose was lower than that in the three-dose group by a factor of 3.5 (95% confidence interval [CI], 2.7 to 4.6) and was lower than that in the internal control group by a factor of 2.3 (95% CI, 1.7 to 3.3). Protection against severe illness did not wane during the 6 weeks after receipt of the fourth dose. The number of cases of confirmed infection per 100,000 person-days (unadjusted rate) was 177 in the aggregated four-dose groups, 361 in the three-dose group, and 388 in the internal control group. In the quasi-Poisson analysis, the adjusted rate of confirmed infection in the fourth week after receipt of the fourth dose was lower than that in the three-dose group by a factor of 2.0 (95% CI, 1.9 to 2.1) and was lower than that in the internal control group by a factor of 1.8 (95% CI, 1.7 to 1.9). However, this protection waned in later weeks.Rates of confirmed SARS-CoV-2 infection and severe Covid-19 were lower after a fourth dose of BNT162b2 vaccine than after only three doses. Protection against confirmed infection appeared short-lived, whereas protection against severe illness did not wane during the study period.
New idea to promote the clinical applications of stem cells or their extracellular vesicles in central nervous system disorders: Combining with intranasal delivery
Authors: Yaosheng Li, Honghui Wu, Xinchi Jiang, Yunfei Dong, Juanjuan Zheng, Jianqing Gao
Journal: Acta Pharmaceutica Sinica B (2022)

The clinical translation of stem cells and their extracellular vesicles (EVs)-based therapy for central nervous system (CNS) diseases is booming. Nevertheless, the insufficient CNS delivery and retention together with the invasiveness of current administration routes prevent stem cells or EVs from fully exerting their clinical therapeutic potential. Intranasal (IN) delivery is a possible strategy to solve problems as IN route could circumvent the brain‒blood barrier non-invasively and fit repeated dosage regimens. Herein, we gave an overview of studies and clinical trials involved with IN route and discussed the possibility of employing IN delivery to solve problems in stem cells or EVs-based therapy. We reviewed relevant researches that combining stem cells or EVs-based therapy with IN administration and analyzed benefits brought by IN route. Finally, we proposed possible suggestions to facilitate the development of IN delivery of stem cells or EVs.