tbuckley/cabot-search huggingface dataset:
Abstract 11680: Comorbidity and Cognitive Function Predict Efficiency of a Disease Management Program in Reducing Short-Term Readmission in Heart Failure
Authors: Quan Huynh, Thomas Marwick
Journal: Circulation (2021)

Background: Both comorbidity and cognitive impairment are highly prevalent and predictive of outcomes in heart failure (HF). We sought whether these risk factors could identify patients most likely to benefit from a HF disease management program (DMP) to reduce readmission. Methods: 1363 consecutive HF patients were prospectively followed for 1 month after discharge. Of these, 431 (31%) patients received a DMP (1-month duration, including post-discharge home visits, medication reconciliation, exercise guidance and early clinical review). Primary outcome was all-cause readmission/death at 30-day post-discharge. Charlson comorbidity index (CCI) was calculated based on discharge diagnoses and categorised as mild (CCI≤2), moderate (CCI 3-4) and severe (CCI≥5). Cognitive function was assessed on discharge using the Montreal Cognitive Assessment (MoCA) and classified as normal (MoCA 26-30), low-normal (MoCA 23-25), mildly impaired (MoCA 17-22) and moderate/severely impaired (MoCA≤16). Results: 28% (386/1363) of patients died or were readmitted within 30 days after discharge. Both CCI (relative risk RR=1.06 [95% CI: 1.03, 1.10] per point) and MoCA (RR=0.95 [95% CI: 0.94, 0.96] per point) were significantly predictive of outcome, with a statistically significant interaction (p=0.032). Cross-classification of CCI and MoCA identified a group of high-risk patients (≥mild cognitive impairment and/or severe Charlson comorbidity index) who had a 2.02-fold higher risk of 30-day readmission/death (34%, 309/903) than patients with mild/moderate CCI and without cognitive impairment (17%, 72/426). The effect size of DMP was significantly stronger (p=0.034) among the high-risk patients (RR=0.62 [95% CI: 0.49, 0.77]) compared to low-risk patients (RR=0.98 [95% CI: 0.61, 1.58]). Conclusion: Comorbidities and cognitive impairment strongly predict short-term adverse outcomes in HF and can be used to identify patients who are most likely to benefit from a DMP.
Is it time to move on to the next generation of clinical trials in older patients with cancer?
Authors: Hannah Lowe, Alastair Greystoke
Journal: The Lancet Healthy Longevity (2021)

Lung cancer is the leading cause of cancer death worldwide and is commonly diagnosed in older patients, with the median age of diagnosis in the UK being 71 years (IQR 62–75).1 Treatment rates, both curative and palliative in intent, decrease with age,2 the reasons for which are complex and might include complications in treatment delivery due to comorbidities, poor functional status, and frailty, which are common in older people. These problems might be more marked in squamous-cell lung cancer, which accounts for 25% of cases of non-small-cell lung cancer (NSCLC), as this type of lung cancer commonly arises in patients who are currently or have previously been smokers and might be associated with smoking-related diseases such as chronic obstructive pulmonary disease, ischaemic heart disease, and peripheral vascular disease.
CTIM-22. NIVOLUMAB AND BEVACIZUMAB FOR RECURRENT GLIOBLASTOMA; T-CELL REACTIVITY AGAINST AUTOLOGOUS TUMOR CELLS
Authors: Simone Maarup, Signe Skadborg, Annie Borch, Arianna Draghi, Benedikte Hasselbalch, Olga Østrup, David Scheie, Jane Skjoeth-Rasmussen, Ian Law, Inge Marie Svane, Hans Poulsen, Sine Hadrup, Ulrik Lassen
Journal: Neuro-Oncology (2021)

Abstract INTRODUCTION Glioblastoma is an aggressive brain tumor with a median survival of 14.6 months. We have no standard treatment for relapse and known options have limited effect. Novel treatments are necessary to improve survival and quality of life. METHODS We present our trial; phase II open label, two-armed translational study of Nivolumab and Bevacizumab for recurrent GBM, who have failed Stupp’s regimen. Patients are included in two arms depending on the possibility of salvage neurosurgical resection. Both arms receive Nivolumab and Bevacizumab administrated every second weekend, and the surgical arm also receive Nivolumab 7 days prior surgery. Forty-four patients were included by January 2021; 20 in each arm (four screen-failures). In the surgical arm, 20 fresh tumor samples as well as paired tissue from primary tumor were available. Tumor infiltrating lymphocytes (TILs) and tumor digest were produced in vitro from recurrent settings. Young TILs were expanded from fresh tumor fragments after minimal-culture, whereas rapidly expanded TILs (REP TILs) were obtained after massive expansion. By intracellular cytokine staining, we investigated the TIL reactivity after exposure to autologous tumor digest in order to evaluate whether the TILs were tumor-reactive, non-reactive or bystanders. RNA and whole exome sequencing were available before and after treatment. RESULTS Material from 19 patients was analyzed (one out of the 20 collected biopsies was limited in size, therefore no tumor digest could be produced). Four out of 19 TIL samples showed tumor reactivity after exposure to the autologous tumor digest. Tumor reactivity was ranged between 1,2 to 13,6 tox% in CD8+ TILs and between 2,8 to 10,9 tox% in CD4+ TILs. By flowcytometry we found, IgG4+ CD3+ TILS from tumor biopsies, meaning that Nivolumab were found in the brain. Currently controls are included to evaluate these results. CONCLUSIONS Updated results will be presented at SNO.
Abstract 13197: Increased Cardiac and All-Cause Mortality After Percutaneous Coronary Intervention in Subclinical Hypothyroidism: A Meta-Analysis
Authors: Sonali Sachdeva, Rupak Desai, Nirmit Patel, TAHA SAEED, Akhil Jain, Harshwardhan Khandait, Ankita Aggarwal, Anubhav Jain
Journal: Circulation (2021)

Background: Subclinical hypothyroidism (elevated TSH with normal thyroid hormone levels), is associated with an increased risk of cardiovascular diseases like atherosclerosis and coronary artery disease. However, its impact on long-term outcomes after percutaneous coronary intervention (PCI) remains understudied. Methods: PubMed, EMBASE, and Web of Science databases were screened through June 2021 for studies reporting long-term PCI outcomes in patients with subclinical hypothyroid state vs. Euthyroid state. Random effects models were used for the meta-analysis. I2 statistics were used to interpret heterogeneity with I 2 &gt;75% indicating substantial inter-study variation. A sensitivity analysis was performed using the leave one out method. A p-value &lt;0.05 was considered statistically significant. Results: A total of 6 studies including 11,664 patients who had undergone PCI were identified with a median follow-up period of 3.75 years. There were 987 patients identified with subclinical hypothyroidism and the mean age of the cohort was 67.15 ± 9.9 years. It consisted of 48% males, the most common comorbidities were hypertension (70%) followed by diabetes mellitus (33%). In-hospital outcomes were reported only in one study while long-term outcomes were reported in all 6 studies. Pooled analysis for long-term adverse events showed that subclinical hypothyroidism was associated with increased all-cause (OR 1.78, 95%CI: 1.16-2.72, p&lt;0.01, I 2 =50.67%) and cardiac mortality (OR 1.41, 95%CI: 1.09=1.81, p&lt;0.01, I 2 =0%) over long-term follow-up following PCI Conclusions: Subclinical hypothyroidism at times remains undiagnosed or underdiagnosed, however, it predicts significantly higher all-cause and cardiac mortality in the long term following PCI compared to controls. Therefore, it is recommended to regularly screen and manage high-risk patients undergoing PCI with underlying subclinical hypothyroidism.
Abstract 10246: Low Polygenic CAD Risk Score is Associated with Coronary Artery Calcium Score of Zero: A Real World Experience
Authors: Muhammad Hamza Saad Shaukat, Veronica Stys, patryk stys, Catherine Hajek, Phillip Petrasko, Melissa Pham, Beatrice Rynders, Mark Petrasko, Alexander Sjovold, Komaldeep Singh, Kevin Coy, Michael Herman, Murat Sincan, Adam Stys, Marian S Petrasko, Tomasz P Stys
Journal: Circulation (2021)

Introduction: Genetic predisposition for CAD is well established. Polygenic risk scores are emerging as tools to quantify the genomic component of an individual’s risk for CAD. However, their clinical utility for individual risk stratification is unclear. Hypothesis: 180 SNPs previously identified in Caucasian Genome Wide-Association Studies for CAD were used to construct a weighted restricted polygenic risk score (PRS; normalized range 11.18 -17.58). This study hypothesizes that a low PRS (&lt;85th percentile) is associated with coronary calcium score (CAC) of zero. Methods: Between January 2018 &amp; March 2020, 21,784 patients underwent CAC screening and/or PRS testing. Caucasian patients with both PRS and CAC scores were identified. Fisher’s exact test was utilized to test the association between low PRS and CAC score of zero. Results: 3,197 Caucasian patients had both PRS and CAC calculated, 1597 (49.9%) of whom had CAC greater than zero. Characteristics are summarized in table 1. Odds ratio of low PRS associated with CAC zero was 1.34 (95% CI 1.08 - 1.67; p=0.0079). Conclusions: In our Caucasian cohort, there is a statistically significant correlation between a low PRS and absence of coronary artery calcium. This is a real-world analysis incorporating genomic data for individual CAD risk stratification. Further studies on a larger, ethnically diverse cohort are needed.
Abstract P390: Gender And Strain Background Affect Cardiopulmonary Function In <i> Col4a3 <sup>-/-</sup> </i> Alport Mice
Authors: Camila Iansen Irion, Monique Williams, Trevor Eisenberg, Grace Seo, Guerline Lambert, Lauro M Takeuchi, Karen C Young, Joshua M Hare, Lina A Shehadeh
Journal: Circulation Research (2021)

Background: Alport syndrome (AS) is a hereditary form of chronic kidney inflammation that results in renal failure (RF). Our group previously reported that Col4a3 -/- mice, a model of AS and RF, on 129J background exemplified multiple features of heart failure with preserved ejection fraction (HFpEF). This study investigates the effect of 3 different genetic backgrounds on cardiopulmonary function in Col4a3 -/- mice. Methods: Male and female Col4a3 -/- (Alport) and WT mice on 3 different genetic backgrounds, 129x1/SvJ, C57Bl/6 and BALBC, were examined using echocardiography, whole body plethysmography (WBP) and pressure-volume (PV) loop analysis. Ttest was used for statistical analysis. Four groups per strain were used (n= 4 to 15 per group). Results: Compared with their respective age-matched WT controls, both male and female 8-week-old Col4a3 -/- 129x1/SvJ mice demonstrated impaired systolic function (EF of 56% to 43.7%, p=0.0018 for females and 50.9% to 42% for males, p=0.044; SV, CO, p&lt;0.05) and diastolic dysfunction (increased IVRT from 15.32ms to 21.72ms, p=0.0009 for females; 16.57ms to 26.21ms, p&lt;0.0001 for males; increased MPI, P&lt;0.05). Additionally, PV loop analysis showed an increased EDPVR and end diastolic pressure, prolonged time constant of LV relaxation, and decreased CO and SV (p&lt;0.05). However for Col4a3 -/- BalbC (8-week-old) and Col4a3 -/- C57Bl/6 (20-week-old) strains, only females exhibited systolic (BalbC: EF% 51% to 45.66%, p=0.106 for females and 43.5% to 40.8% for males, p=0.508; B6: EF% 51.30% to 40.80% p=0.024 for females and 48.43% to 40.91%, p=0.3098 for males; SV, CO, p&lt;0.05) and diastolic dysfunction (IVRT from 15.96ms to 24.91ms for Balb/C and 18.20ms to 25.63ms for B6, p&lt;0.05). Male Col4a3 -/- BalbC had an increase in minimum pressure and end-systolic pressure, and an increased pressure at dV/dt-max. Male Col4a3 -/- C57Bl/6 mice had an increased ESPVR slope (p&lt;0.05). All strains except BalbC males demonstrated alterations (p&lt;0.05) in pulmonary function including decreased ventilation rate (MV, mL/min) and respiratory frequency (BPM), decreased peak expiratory flow, EF50, increased expiratory time, relaxation time, inspiratory time, and time of pause at end-of-expiration. Conclusion: Both male and female Col4a3 -/- 129x1/SvJ mice demonstrated impaired cardiopulmonary viability. However, Col4a3 -/- mice on BalbC or C57Bl/6 strains had cardiopulmonary deficits only in females.
Abstract 11924: Guiding Strategies in Tricuspid Edge-to-Edge Intervention
Authors: Tobias F Ruf, Walid Ben Ali, Patrick Gerdes, Jaqueline G da Rocha e Silva, Felix Kreidel, Alexander Tamm, Martin Geyer, Thomas Muenzel, Ralph Stephan von Bardeleben
Journal: Circulation (2021)

Introduction: Echocardiographical guiding gains further importance as transcatheter interventions for heart valve diseases advance. In transcatheter edge-to-edge repair for tricuspid regurgitation (TEER-TR), the use of transesophageal echocardiography (TEE) employing biplane imaging with views perpendicular to the inflow-outflow-view is suggested. However, robust data on echocardiographical guiding in this setting is lacking, as well as on the role of fluoroscopy settings. Hypothesis: The aim of the study was to evaluate different guiding-approaches and fluoroscopy settings in TEER-TR procedures. Methods: We retrospectively assessed the effect of different echocardiographical guiding strategies and fluoroscopy angulations on immediate TR reduction (ΔTR), and device time in the TEER-TR interventions. Echocardiographical guiding was rated using a new quality scoring system, MACES 3 . Results: From July 2016 to December 2019 a total of 190 cases of TEER-TR procedures were conducted. In all but 2, the procedure was successfully completed. Device deployment was achieved using transesophageal imaging in 65 cases (n[mid-esophageal]=47, (midE); n[deep-esophageal]=18, (deepE)), while live-MPR was employed 4 times. The transgastric en-face view (TG) constituted the grasping view 119 times (Fig. 1). The best imaging quality with the highest MACES 3 scores were observed in deepE and TG. MACES 3 scores significantly influenced the acute outcome. In cases of secondary TR, the use of TG was superior to other imaging in achieving a ΔTR of ≥ 2 grades. Both the use of TG and special fluoroscopy alignment significantly reduced the device time. Conclusions: TEER-TR can be effectively guided using different echocardiographic strategies. To strive for the best imaging quality clearly increases procedural success. Using the TG approach offers benefits in immediate procedural result and device time, with the latter further reduced using fluoroscopic alignment.
Abstract 12262: The Role of Machine Learning-Based Decision Support Tools for Diagnosing and Assessing Congenital Heart Disease
Authors: Stephanie Helman, Elizabeth Herrup, Adam Christopher, Salah S Al-Zaiti
Journal: Circulation (2021)

Introduction: Machine learning (ML) is frequently applied in healthcare to optimize diagnostic classification through discovery of hidden patterns in data, not obvious to the human brain. ML research in CHD entails one of the most promising clinical applications, where timely and accurate diagnosis is essential. The objective of this scoping review was to summarize the accuracy and role of ML techniques used in pediatric cardiology research, specifically focusing on approaches that optimize diagnosis and assessment of underlying CHD. Methods: All original, peer-reviewed studies published in PubMed between January 2015 and February 2021 describing “(machine learning) AND ((congenital heart disease) OR (cardiovascular disease in children))” for predicting diagnostic outcomes in children with critical and non-critical CHD were included. An independent reviewer extracted and summarized primary data elements using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews guidelines. Results: This search yielded 217 journal articles of which 48 full-text articles (22%) met inclusion criteria. The most common application included optimizing the diagnosis and assessment of critical and non-critical CHD (38%). Deep learning (48%) and support vector machine (19%) were the most common ML algorithms used, with more interpretable algorithms being less common including decision trees (5%). Studies focusing on optimizing diagnostic classification reported a pooled overall diagnostic accuracy ranging from of 0.864 to 0.955, but only two of these models were externally validated. Clinical applications primarily focused on the classification of auscultatory heart sounds, transthoracic echocardiograms, and cardiac magnetic resonance images. Conclusions: These findings indicate that ML is a very promising tool for diagnosing and assessing critical and non-critical CHD, yet extensive research is still needed to build interpretable, robust, and generalizable models for clinical use, especially considering the extreme heterogeneity of complex CHD.
RBIO-02. THERAPEUTIC EFFECTS OF RADIOTHERAPY WITH CONCOMITANT IN CHILDREN WITH DIPG
Authors: Mingyao Lai, Shaoqun Li, Juan Li, Qingjun Hu, Junjie Zhen, Jiangfen Zhou, Linbo Cai, zhaoming Zhou
Journal: Neuro-Oncology (2021)

Abstract OBJECTIVE To retrospectively analyze the therapeutic effects of radiotherapy with concomitant and adjuvant temozolomide（TMZ） versus radiotherapy with concomitant TMZ alone for pediatric diffuse intrinsic pontine glioma (DIPG), and to evaluate the value of radiotherapy and TMZ in the treatment of pediatric DIPG. METHODS The clinical data of children with confirmed DIPG in Guangdong Sanjiu Brain Hospital between January 1, 2010 and March 31, 2020 were collected. The inclusive criteria included (1) receiving a total radiotherapy dose of 54 Gy in 27 fractions, (2) treated with concomitant TMZ chemotherapy, and (3) with or without adjuvant TMZ chemotherapy. A total of 85 pediatric patients were eligible for the study. The Kaplan-Meier method was used for survival analysis, and a multivariable Cox proportional hazards regression model was used to assess the independent prognostic factors. RESULTS Among 85 cases with a median age of 7 years (range 2-16 years), the median follow-up was 9 months (range 3-28 months) and the median survival time was 9 months. The median survival time of 66 patients treated with radiotherapy with concomitant and adjuvant TMZ was 10 months, longer than 6 months of the other 19 patients treated with radiotherapy with concomitant TMZ alone, with statistical differences (p=0.002). Moreover, bevacizumab and nimotuzumab didn't bring survival benefits to patients with disease recurrence or progression. The prognosis in DIPG patients with H3K27M positive expressed is poor. Hematological toxicity (Grade IV) was not found. CONCLUSION Radiotherapy with concomitant and adjuvant TMZ prolongs the survival time of children with DIPG.
Development and validation of a patient-reported outcome measure for systemic sclerosis: the EULAR Systemic Sclerosis Impact of Disease (ScleroID) questionnaire
Authors: Mike O Becker, Rucsandra Dobrota, Alexandru Garaiman, Rudolf Debelak, Kim Fligelstone, Ann Tyrrell Kennedy, Annelise Roennow, Yannick Allanore, Patricia E Carreira, László Czirják, Christopher P Denton, Roger Hesselstrand, Gunnel Sandqvist, Otylia Kowal-Bielecka, Cosimo Bruni, Marco Matucci-Cerinic, Carina Mihai, Ana Maria Gheorghiu, Ulf Mueller-Ladner, Joseph Sexton, Tore K Kvien, Turid Heiberg, Oliver Distler
Journal: Annals of the Rheumatic Diseases (2021)

Patient-reported outcome measures (PROMs) are important for clinical practice and research. Given the high unmet need, our aim was to develop a comprehensive PROM for systemic sclerosis (SSc), jointly with patient experts.This European Alliance of Associations for Rheumatology (EULAR)-endorsed project involved 11 European SSc centres. Relevant health dimensions were chosen and prioritised by patients. The resulting Systemic Sclerosis Impact of Disease (ScleroID) questionnaire was subsequently weighted and validated by Outcome Measures in Rheumatology criteria in an observational cohort study, cross-sectionally and longitudinally. As comparators, SSc-Health Assessment Questionnaire (HAQ), EuroQol Five Dimensional (EQ-5D), Short Form-36 (SF-36) were included.Initially, 17 health dimensions were selected and prioritised. The top 10 health dimensions were selected for the ScleroID questionnaire. Importantly, Raynaud's phenomenon, impaired hand function, pain and fatigue had the highest patient-reported disease impact. The validation cohort study included 472 patients with a baseline visit, from which 109 had a test-retest reliability visit and 113 had a follow-up visit (85% female, 38% diffuse SSc, mean age 58 years, mean disease duration 9 years). The total ScleroID score showed strong Pearson correlation coefficients with comparators (SSc-HAQ, 0.73; Patient's global assessment, Visual Analogue Scale 0.77; HAQ-Disability Index, 0.62; SF-36 physical score, -0.62; each p<0.001). The internal consistency was strong: Cronbach's alpha was 0.87, similar to SSc-HAQ (0.88) and higher than EQ-5D (0.77). The ScleroID had excellent reliability and good sensitivity to change, superior to all comparators (intraclass correlation coefficient 0.84; standardised response mean 0.57).We have developed and validated the EULAR ScleroID, which is a novel, brief, disease-specific, patient-derived, disease impact PROM, suitable for research and clinical use in SSc.
Abstract 10678: Butyrate Improves Energetics, Diastolic Function and Contractile Reserve in Hearts from Mice with Hypertrophic Cardiomyopathy Due to Myosin R403Q Mutation
Authors: Tomas Baka, Dominique Croteau, Jordan Chambers, Huamei He, James Balschi, Fuzhong Qin, Wilson S Colucci, David Pimentel, Ivan Luptak
Journal: Circulation (2021)

Background: It is well established that hearts with hypertrophic cardiomyopathy (HCM) are energy starved as reflected by a decreased phosphocreatine to ATP ratio that corresponds to increased ADP and decreased free energy of ATP hydrolysis (ΔG ~ATP ). Notably, worsened energetics precedes hypertrophy in development of HCM and mitochondrial mutations impeding ATP synthesis frequently lead to a hypertrophic phenotype similar to HCM. It remains unclear whether targeted strategies to boost mitochondrial ATP synthesis may improve chronically depressed diastolic function and contractile reserve. Here we hypothesize that saturating mitochondria with an accessible substrate, butyrate, acutely improves energetics and function in HCM. Methods and Results: Isolated hearts from 6 months old mice with HCM due to R403Q myosin mutation (R403Q) vs. the wild type littermates (WT) were studied using 31 P NMR spectroscopy to measure ATP synthesis, ADP and ΔG ~ATP at low (LW) and high workload (HW) and HW plus 4 mM butyrate (HWB). As expected, compared to WT, R403Q hearts showed: ↑ATP synthesis associated with a trend for ↑rate pressure product (RPP, p=0.08) at LW but were unable to increase these parameters further at HW. Energetics (↑ADP and ↓ΔG ~ATP ) were depressed at LW and worsened further at HW. Diastolic dysfunction (↑EDP) developed at HW. Butyrate perfusion (HWB) significantly improved all energetic and contractile parameters in R403Q hearts. Conclusion: Here we show that mouse hearts with HCM due to myosin R403Q mutation have worsened energetics despite a higher ATP synthesis rate at baseline. With higher work demand R403Q hearts are unable to dynamically increase ATP synthesis or work. Acute saturation with butyrate enables a further increase in ATP synthesis, normalizing energetics and improving diastolic function and contractile reserve. Thus, our results suggest that targeting mitochondrial function may be a promising strategy in management of HCM.