tbuckley/cabot-search huggingface dataset:
Dose Painting
Authors: Shivani Sud
Journal: Journal of Clinical Oncology (2022)

When asked to describe radiation oncology, my first recollection is watching chart rounds as a medical student.Sitting along the conference room periphery, I observed as dosimetrists projected patients' scans, residents presented histories, and attending physicians reviewed treatment plans.Far from the usual hospital rounds with plans consisting of procedures, consults, and medication changes-here, treatment plans are scans overlaid with intricate colorful lines denoting the amount of radiation traversing internal structures to arrive at the target (ie, tumor) volume.This dose visualization is our primary method of conceptualizing and articulating radiotherapy treatments.Recent technological advances enable delivery of radiation with immense precision to the extent we dub some techniques as "dose painting." 1 Starting with our planning scan consisting of computed tomography images of the patient in the treatment position, we delineate areas of tumor and likely microscopic disease to compose our target volumes.In collaboration with dosimetrists and physicists, we adjust various parameters including multileaf collimators-movable metal leaves that sculpt the xray beam as it departs the linear accelerator to enter the patient-and beam angles such that we cover the intended target with radiation while avoiding delicate neighboring organs.We evaluate and iteratively optimize our radiation plans and the resultant dose distribution.Balancing the correct radiation dose, treatment field size, and shape are critical for preventing recurrence, minimizing toxicity, and improving survival.
The Chronic Conditions Course: A Randomised Controlled Trial of an Internet-Delivered Transdiagnostic Psychological Intervention for People with Chronic Health Conditions
Authors: Blake F. Dear, Amelia J. Scott, Rhiannon Fogliati, Milena Gandy, Eyal Karin, Joanne Dudeney, Olav Nielssen, Sarah McDonald, Andreea I. Heriseanu, Madelyne A. Bisby, Louise Sharpe, Michael P. Jones, Shehzad Ali, Nickolai Titov
Journal: Psychotherapy and Psychosomatics (2022)

&lt;b&gt;&lt;i&gt;Introduction:&lt;/i&gt;&lt;/b&gt; Psychological adjustment to chronic health conditions is important, as poor adjustment predicts a range of adverse medical and psychosocial outcomes. Psychological treatments demonstrate efficacy for people with chronic health conditions, but existing research takes a disorder-specific approach and they are predominately delivered in face-to-face contexts. The internet and remotely delivered treatments have the potential to overcome barriers to accessing traditional face-to-face treatment. &lt;b&gt;&lt;i&gt;Objective:&lt;/i&gt;&lt;/b&gt; The current study examined the efficacy and acceptability of an internet-delivered transdiagnostic psychological intervention to promote adjustment to illness, based on cognitive behaviour therapy principles. &lt;b&gt;&lt;i&gt;Methods:&lt;/i&gt;&lt;/b&gt; In a two-arm randomised controlled trial, participants (&lt;i&gt;n&lt;/i&gt; = 676) were randomly allocated to the 8-week intervention or a waitlist control. Treatment included five core lessons, homework tasks, additional resources, and weekly contact with a psychologist. Primary outcomes included depression, anxiety, and disability, assessed at pre-treatment, post-treatment, 3-month follow-up, and 12-month follow-up. &lt;b&gt;&lt;i&gt;Results:&lt;/i&gt;&lt;/b&gt; The treatment group reported significantly greater improvements in depression (between-groups &lt;i&gt;d =&lt;/i&gt; 0.47), anxiety (&lt;i&gt;d&lt;/i&gt; = 0.32), and disability (&lt;i&gt;d&lt;/i&gt; = 0.17) at post-treatment (all &lt;i&gt;ps&lt;/i&gt; &amp;#x3c;0.001). Improvements were sustained over the 3-month and 12-month follow-ups. High treatment completion rates (69%) and levels of satisfaction (86%) were reported by participants in treatment. The intervention required a mean clinician time of 56.70 min per participant. &lt;b&gt;&lt;i&gt;Conclusions:&lt;/i&gt;&lt;/b&gt; The findings provide preliminary and tentative support for the potential of internet-delivered transdiagnostic interventions to promote adjustment to chronic health conditions. Further research using robust control groups, and exploring the generalisability of findings, is needed before firm conclusions can be drawn.
169P Characteristics of clonal hematopoiesis (CH) in patients with non-small cell lung cancer (NSCLC): A retrospective analysis of plasma cell-free DNA (cfDNA) comprehensive genomic profiling
Authors: M. Tagliamento, D. Vasseur, None A. Bayle, M. Aldea, A. Gazzah, C. Nicotra, A. Hollebecque, D. Planchard, M. Frelaut, A. Botticella, A. Levy, L. Lacroix, C. Marzac, J.B. Micol, S. Ponce, E. Rouleau, A. Italiano, B. Besse
Journal: Annals of Oncology (2022)
Abstract P201: Social Determinants Of Health Modulate Risk Of Heart Failure Development In A Federally Qualified Health Center Population
Authors: Tejas Joshi, Adovich Rivera, Megan Plank, Laura Rusie, Lauren B Beach
Journal: Circulation (2022)

Introduction: Social determinants of health (SDoH) are known predictors of heart failure, though their incorporation into existing risk models is limited, and these models are not widely implemented. In particular, there are limited studies of heart failure risk within federally qualified health centers (FQHCs) tailored to quantify the effects of several SDoH including sexual and gender minority status, socioeconomic factors, and neighborhood characteristics. Hypothesis: We assessed the hypothesis that risk factors among several SDoH domains would modulate heart failure risk when controlled for traditional biologic risk factors and significantly improve the performance of a predictive model among patients at Howard Brown Health, a FQHC. Methods: We retrospectively identified all patients at Howard Brown Health from January 1, 2012 through December 31, 2019 using electronic health records. The association between risk factors and heart failure diagnosis, defined as having one heart failure-associated ICD code, was assessed by multivariate logistic regression. Missing data were imputed with the R mice package. Neighborhood-level data were obtained from the 2019 American Community Survey. Machine learning was used to predict heart failure with several algorithms including gradient boosting machine via the R caret package. Results: Among 99,047 patients, 130 (0.13%) had heart failure. On multivariate logistic regression, these patients were significantly more likely than peers to be older (OR 0.0002, p&lt;0.001), smoke (OR = 0.0035, p&lt;0.001), have diabetes (OR 0.3, p&lt;0.001), have dyslipidemia (OR 0.3, p&lt;0.001), have hypertension (OR 0.001, p&lt;0.001) or have coronary heart disease (OR 0.8, p&lt;0.001. Non-Hispanic whites were at lower risk than non-Hispanic blacks (OR 0.0008, p&lt;0.01) and at higher risk than Hispanic patients (OR -0.0006, p&lt;0.05). Patients with lower household incomes, government insurance or no insurance, or those who lived in neighborhoods with lower median household incomes were also all more likely to have heart failure (all p&lt;0.05). The machine learning predictive models incorporating SDoH and without SDoH respectively had sensitivities of 87% and 82%, specificities of 85% and 80%, positive predictive values of 99.98% and 99.98%, and negative predictive values of 0.9% and 0.8%. Conclusions: Biologic comorbidities portend the highest heart failure risk. Race and economic factors, including neighborhood level variables, predict the highest heart failure risk among measured SDoH in this FQHC population. A machine learning model is able to predict heart failure with biologic comorbidities, and SDoH improve model performance. In conclusion, future research incorporating SDoH—in particular race and economic characteristics—into risk assessments or predictive modeling may aid early detection and prevention of heart failure and reduce health disparities.
Vaccination of human participants with attenuated Necator americanus hookworm larvae and human challenge in Australia: a dose-finding study and randomised, placebo-controlled, phase 1 trial
Authors: Paul R Chapman, Rebecca Webster, Paul Giacomin, Stacey Llewellyn, Luke Becker, Mark S Pearson, Fabian De Labastida Rivera, Peter O'Rourke, Christian R Engwerda, Alex Loukas, James S McCarthy
Journal: The Lancet Infectious Diseases (2021)
Association of Differential Mast Cell Activation with Granulocytic Inflammation in Severe Asthma
Authors: Angelica Tiotiu, Yusef Badi, Nazanin Zounemat Kermani, Marek Sanak, Johan Kolmert, Craig E. Wheelock, Philip M. Hansbro, Sven-Erik Dahlén, Peter J. Sterk, Ratko Djukanovic, Yike Guo, Sharon Mumby, Ian M. Adcock, Kian Fan Chung, Uruj Hoda, Christos Rossios, Elisabeth Bel, Navin Rao, David Myles, Chris Compton, Marleen Van Geest, Peter Howarth, Graham Roberts, Diane Lefaudeux, Bertrand De Meulder, Aruna T. Bansal, Richard Knowles, Damijn Erzen, Scott Wagers, Norbert Krug, Tim Higenbottam, John Matthews, Veit Erpenbeek, Leon Carayannopoulos, Amanda Roberts, David Supple, Pim deBoer, Massimo Caruso, Pascal Chanez, Ildikó Horváth, Jacek Musial, Thomas Sandström
Journal: American Journal of Respiratory and Critical Care Medicine (2021)

Rationale: Mast cells (MCs) play a role in inflammation and both innate and adaptive immunity, but their involvement in severe asthma (SA) remains undefined. Objectives: We investigated the phenotypic characteristics of the U-BIOPRED (Unbiased Biomarkers for the Prediction of Respiratory Diseases Outcomes) asthma cohort by applying published MC activation signatures to the sputum cell transcriptome. Methods: Eighty-four participants with SA, 20 with mild/moderate asthma (MMA), and 16 healthy participants without asthma were studied. We calculated enrichment scores (ESs) for nine MC activation signatures by asthma severity, sputum granulocyte status, and three previously defined sputum molecular phenotypes or transcriptome-associated clusters (TACs) 1, 2, and 3 using gene set variation analysis. Measurements and Main Results: MC signatures except unstimulated, repeated FcεR1-stimulated and IFN-γ–stimulated signatures were enriched in SA. A FcεR1-IgE–stimulated and a single-cell signature from asthmatic bronchial biopsies were highly enriched in eosinophilic asthma and in the TAC1 molecular phenotype. Subjects with a high ES for these signatures had elevated sputum amounts of similar genes and pathways. IL-33– and LPS-stimulated MC signatures had greater ES in neutrophilic and mixed granulocytic asthma and in the TAC2 molecular phenotype. These subjects exhibited neutrophil, NF-κB (nuclear factor-κB), and IL-1β/TNF-α (tumor necrosis factor-α) pathway activation. The IFN-γ–stimulated signature had the greatest ES in TAC2 and TAC3 that was associated with responses to viral infection. Similar results were obtained in an independent ADEPT (Airway Disease Endotyping for Personalized Therapeutics) asthma cohort. Conclusions: Gene signatures of MC activation allow the detection of SA phenotypes and indicate that MCs can be induced to take on distinct transcriptional phenotypes associated with specific clinical phenotypes. IL-33–stimulated MC signature was associated with severe neutrophilic asthma, whereas IgE-activated MC was associated with an eosinophilic phenotype.
Abstract 10724: Long-Term Mortality After Acute Coronary Syndromes Among Patients with Normal, Mid-Range or Low Ejection Fraction
Authors: Remo Furtado, Marcela G Juliasz, FELIPE Y CHIU, Livia B Bastos, Talia F Dalcoquio, Felipe G Lima, Renato Rosa, Cesar A Caporrino, Adriadne Bertolin, Carla Soffiatti, Andre S Ribeiro, Maria C Andrade, Roberto Giraldez, Luciano Baracioli, Jose C Nicolau
Journal: Circulation (2021)

Introduction: Left ventricle ejection fraction (LVEF) is a well-established marker for survival after acute coronary syndromes (ACS). While there has been strong association between low ejection fraction (i.e., LVEF &lt; 40%) and mortality, the long-term prognostic impact of mid-range EF (LVEF 40-49%) after ACS remains less clear. Methods: This was a retrospective study enrolling consecutive patients admitted with ACS included in a single tertiary center databank. LVEF was assessed by echocardiography during index hospitalization. Patients were divided in the following categories according to LVEF: normal (LVEF ≥ 50%), mid-range (40-49%) and low (&lt; 40%). The endpoint of interest was all-cause death after hospital discharge. A multivariable Cox regression model was used to adjust for confounders. The model was adjusted for age, sex, race, history of diabetes mellitus, prior HF, arterial hypertension, dyslipidemia, smoking, STEMI versus non-ST elevation ACS, prior MI, prior PCI, prior CABG, creatinine and Killip class at admission Results: A total of 3200 patients were included (1,952 with normal EF; 659 with mid-range EF and 589 with low EF); mean age was 63.5 ± 12.4 years (63.2±12.3, 63.9±12.7 and 64.2±12.4 years, respectively for normal, mid-range and low EF; p = 0.14); 2216 (69.3%) were male and 1257 (39.3%) presented with STEMI. The median follow-up time was 5 years, and the maximum follow-up time was 17.8 years. Overall results are shown in the Figure 1. In a sensitivity analysis using a different definition for mid-range EF (36-54%), results remained similar (data not shown). Conclusion: In ACS patients discharged alive from hospital, mid-range EF measured in the acute phase was associated with increased long-term mortality compared to patients with normal EF. This magnitude of effect was similar to that observed for patients with low EF. These data reinforce the need to consider anti-remodeling therapies also for ACS patients who have LVEF in the mid-range.
International Differences in the Frequency of Chronic Obstructive Pulmonary Disease Exacerbations Reported in Three Clinical Trials
Authors: Peter M. A. Calverley, Fernando J. Martinez, Jørgen Vestbo, Christine R. Jenkins, Robert Wise, David A. Lipson, Nicholas J. Cowans, Julie Yates, Courtney Crim, Bartolome R. Celli
Journal: American Journal of Respiratory and Critical Care Medicine (2022)

Rationale: Exacerbations of chronic obstructive pulmonary disease (COPD) are an important endpoint in multinational clinical treatment trials, but the observed event rate is often lower than anticipated and appears to vary between countries. Objectives: We investigated whether systematic differences in national exacerbation rates might explain this observed variation. Methods: We reviewed data from three large multicenter international randomized trials conducted over an 18-year period with different designs and clinical severities of COPD, comparing bronchodilator and/or inhaled corticosteroids with bronchodilators alone and/or placebo. Exacerbations were defined by antibiotic and/or oral corticosteroid use (moderate) or need for hospitalization (severe). We calculated crude exacerbation rates in the 30 countries contributing 30 or more patients to at least two trials. We grouped data by exacerbation rate based on their first study contribution. Measurements and Main Results: For the 29,756 patients in 41 countries analyzed, the mean exacerbation rate was two- to threefold different between the highest and lowest tertiles of the recruiting nations. These differences were not explained by demographic features, study protocol, or reported exacerbation history at enrollment. Of the 18 countries contributing to all trials, half of those in the highest and half in the lowest tertiles of exacerbation history remained in these groups across trials. Severe exacerbations showed a different rank order internationally. Conclusions: Countries contributing to COPD trials differ consistently in their reporting of healthcare-defined exacerbations. These differences help explain why large studies have been needed to show differences between treatments that decrease exacerbation risk.
Abstract 11204: Emulating the Cardiac Mechanical and Humoral Cues to Prolong Human Heart Slice Culture
Authors: Moustafa Meki, Jessica Miller, Qinghui Ou, Ahmad Gebreil, AbouBakr Salama, Xianliang Tang, Riham Abouleisa, Ayman S El-Baz, Guruprasad Giridharan, Tamer Mohamed
Journal: Circulation (2021)

Introduction: Drug induced cardiotoxicity is a major cause of market withdrawal. The limited availability of human heart tissue has led to inaccurate interpretations of cardiac related drug effects. Our group had developed a culture system for pig/human heart slices that is functionally and structurally viable 6 days under electric stimulation and enriched media and could reliably demonstrate the subacute toxic effect of anti-cancer therapeutics. However, by day 10, the slices underwent cardiomyocyte dedifferentiation and fibrotic remodeling, making them inadequate for long-term cardiotoxicity testing. Aims: Including physiological mechanical and humoral cues within the culture system can prolong the viability of the human heart tissue in culture. Methods and Results: Following small molecule screening, we found that incorporation of 100 nM Tri-iodo-thyronine (T3) and 1 μM Dexamethasone (Dex) into our culture media preserved microscopic structure for 12 days in pig and human slices. However, RNA sequencing revealed a significant down regulation in cardiac contractile genes as early as day 8 in culture. To address this, we developed a novel bioengineered Cardiac Tissue Culture Model (CTCM) that can electro-mechanically stimulate heart slices with physiological preload and afterload during each cardiac cycle (Figure 1). Transcriptionally, combining CTCM with T3/Dex treatment, CTCM system was able to maintain the cardiac contractile gene expression at the same levels as the fresh hear tissue. Functionally, heart slices cultured in our CTCM with T3/Dex treatment, completely preserved structural viability and metabolic activity for 12 days. Conclusion: This study demonstrates a new physiological culture system for human heart slices that provides physiological mechanical and humoral cues for maintaining viability and functionality of the heart slices. CTCM may be an ideal platform for chronic cardiotoxicity testing.
Abstract MP41: Associations Of Neighborhood Food And Physical Activity Environments In Young Adulthood With Cardiovascular Health (CVH) In Midlife: The Coronary Artery Risk Development In Young Adults (CARDIA) Study
Authors: Seong Park, Mandy Wong, Kiarri N Kershaw, Catarina I Kiefe, Penny Gordon-larsen
Journal: Circulation (2022)

Background: Adults who maintain high CVH profiles up to midlife have lower risk of several chronic diseases and better quality of life. However, the relationship between the access to different neighborhood resources in young adulthood and the maintenance of CVH into midlife remain understudied. Methods: We used data from 2,317 CARDIA participants. Measures of the neighborhood food and physical activity environment (Table) were linked to participant addresses collected at the baseline exam (1985-1986), when participants were 18-30 years old. CVH was measured at baseline and the year 30 follow-up exam. We examined associations of neighborhood food and physical activity environments with year 30 CVH scores (moderate vs. high and low vs. high) using multinomial logistic regression. Individual- and neighborhood-level covariates (Table) were adjusted for sequentially. Results: At baseline, 31% of participants had high and 5% had low CVH scores, respectively, whereas 11% had high and 34% had low CVH scores 30 years later. At year 30, compared to those with low CVH scores, participants with high CVH scores had better baseline neighborhood conditions (e.g., mean distance to nearest major park 4767m vs. 7043m, mean count of community and public physical activity facilities 50.70 vs. 43.57, mean percentage of food outlets that are supermarkets 0.75% vs. 0.44%) and were more likely to be female (70.99% vs. 59.21%) and White (86.64% vs. 39.14%). In adjusted models, participants who lived in neighborhoods with a higher percentage of supermarkets and more community and public physical activity facilities were less likely to have low CVH scores compared to high CVH scores (Table). Participants who lived in neighborhoods with a higher percentage of convenience stores and further from a major park were more likely to have low vs. high CVH scores. Conclusion: Improving access to physical activity and healthy food resources in young adulthood may have significant implications in longevity and quality of life in midlife.
Safety of Empagliflozin in Patients With Type 2 Diabetes and Chronic Kidney Disease: Pooled Analysis of Placebo-Controlled Clinical Trials
Authors: Katherine R. Tuttle, Adeera Levin, Masaomi Nangaku, Takashi Kadowaki, Rajiv Agarwal, Sibylle J. Hauske, Amelie Elsäßer, Ivana Ritter, Dominik Steubl, Christoph Wanner, David C. Wheeler
Journal: Diabetes Care (2022)

OBJECTIVE To assess the safety of empagliflozin in patients with type 2 diabetes and moderate to severe chronic kidney disease (CKD) (category G3–4) enrolled in clinical trials. RESEARCH DESIGN AND METHODS This analysis pooled data from 19 randomized, placebo-controlled, phase 1–4 clinical trials and 1 randomized, placebo-controlled extension study in which patients received empagliflozin 10 mg or 25 mg daily. Time to first occurrence of adverse events (AEs) was evaluated using Kaplan-Meier analysis and multivariable Cox regression models. RESULTS Among a total of 15,081 patients who received at least one study drug dose, 1,522, 722, and 123 were classified as having G3A, G3B, and G4 CKD, respectively, at baseline. Demographic and clinical characteristics were similar between treatment groups across CKD categories. Rates of serious AEs, AEs leading to discontinuation, and events of special interest (including lower limb amputations and acute renal failure [ARF]) were also similar between empagliflozin and placebo across CKD subgroups. In adjusted Cox regression analyses, risks for volume depletion and ARF were similar for empagliflozin and placebo in the combined group with CKD categories G3B and G4 and the G3A group. Notably lower risks were observed in both groups for hyperkalemia (hazard ratio 0.59 [95% CI 0.37–0.96, P = 0.0323] and 0.48 [0.26–0.91, P = 0.0243], respectively) and edema (0.47 [0.33–0.68, P &amp;lt; 0.0001] and 0.44 [0.28–0.68, P = 0.0002], respectively). CONCLUSIONS Use of empagliflozin in patients with type 2 diabetes and advanced CKD raised no new safety concerns and may have beneficial effects on the development of hyperkalemia and edema.