tbuckley/cabot-search huggingface dataset:
Association of Psoriasis With Incident Venous Thromboembolism and Peripheral Vascular Disease
Authors: Tai-Li Chen, Ling-Ling Lee, Huei-Kai Huang, Jen-Hung Wang, Li-Yu Chen, Hou-Ren Tsai, Ching-Hui Loh, Ching-Chi Chi
Journal: JAMA Dermatology (2021)

<h3>Importance</h3> Psoriasis, venous thromboembolism (VTE), and peripheral vascular disease (PVD) share similar mechanisms involving chronic inflammation. However, the associations between psoriasis and VTE or PVD are unclear. <h3>Objective</h3> To determine the association of psoriasis with incident VTE and PVD. <h3>Data Sources</h3> MEDLINE, Embase, Cochrane Library, Web of Science, and Cumulative Index to Nursing and Allied Health Literature were systematically searched for relevant publications from their respective inception through May 21, 2021. No restrictions on language or geographic locations were imposed. <h3>Study Selection</h3> Two authors independently selected cohort studies that investigated the risk for incident VTE or PVD in patients with psoriasis. Any discrepancy was resolved through discussion with 2 senior authors until reaching consensus. Only 13 initially identified studies met the selection criteria for qualitative review, and only 9 of these for quantitative analysis. <h3>Data Extraction and Synthesis</h3> The Meta-analysis of Observational Studies in Epidemiology (MOOSE) reporting guideline was followed. Two authors independently extracted data and assessed the risk of bias of included studies by using the Newcastle-Ottawa Scale. Disagreements were resolved by discussion with 2 other authors. A random-effects model meta-analysis was conducted to calculate the pooled hazard ratios (HRs) with the corresponding confidence intervals for incident VTE and PVD. Subgroup analyses based on arthritis status, psoriasis severity, sex, and geographic location were also performed. <h3>Main Outcomes and Measures</h3> Hazard ratios for incident VTE and PVD associated with psoriasis. <h3>Results</h3> A total of 13 cohort studies with 12 435 982 participants were included. The meta-analysis demonstrated a significantly increased risk for incident VTE (pooled HR, 1.26; 95% CI, 1.08-1.48) and PVD (pooled HR, 1.27; 95% CI, 1.16-1.40) among patients with psoriasis. Subgroup analyses illustrated increased risk for incident VTE among participants with psoriatic arthritis (pooled HR, 1.24; 95% CI, 1.01-1.53), women (pooled HR, 1.89; 95% CI, 1.36-2.61), and those in Asia (pooled HR, 2.02; 95% CI, 1.42-2.88) and Europe (pooled HR, 1.28; 95% CI, 1.06-1.53). <h3>Conclusions and Relevance</h3> This systematic review and meta-analysis found an increased risk for incident VTE and PVD among patients with psoriatic disease. Typical presentations of VTE or PVD should not be overlooked in patients with psoriasis. Risk factors, such as obesity, physical inactivity, smoking, and varicose veins, should be identified and treated in patients with psoriasis, and medications like hormone-related therapies should be prescribed with caution.
INNV-28. POTENTIAL EFFECTIVE CONSOLIDATION THERAPY WITH SINGLE AGENT IBRUTINIB FOR A CASE WITH PRIMARY CNS LYMPHOMA AFTER INITIAL HD-MTX AND RITUXIMAB INDUCTION THERAPY
Authors: Steven Du, Uvin Ko, Daniela Bota, Xiao-Tang Kong
Journal: Neuro-Oncology (2021)

Abstract INTRODUCTION Primary CNS Lymphoma (PCNSL) is a rare and aggressive cancer that originates from lymphocytes and develops in the central nervous system. Standard induction therapy involves high-dose methotrexate (HD-MTX)-based chemotherapy, which achieves complete or partial response in most PCNSL patients. However, there is no standard consolidation therapy. We report one case in which ibrutinib, a Bruton’s tyrosine kinase inhibitor, replaced low-dose WBRT as consolidation therapy after induction by HD-MTX and rituximab. Ibrutinib treatment yielded good tolerance and further resolution of small residue lymphoma. CASE REPORT The patient is a 77-year-old female who presented with slurred speech, right-sided weakness, and difficulty word-finding in early 2020. Brain MRI found multifocal lesions, and biopsy of the largest lesion near the left lateral ventricle revealed diffuse large B cell lymphoma. The patient began HD-MTX at 6 g/m2 for the first cycle of induction therapy. She continued HD-MTX every two weeks, but dosage was reduced every cycle due to worsening renal function. Ultimately, MTX was discontinued after 6 cycles. Brain MRI showed significant response after HD-MTX except for small residue lymphoma at the biopsy area. 2nd line regimen rituximab and temozolomide was given to complete induction. Brain MRI was stable, but the small enhancing residue lymphoma at left peri-ventricle area was persistent after the induction therapy (uCR). Ibrutinib as consolidation therapy began after discussion with the patient. The patient tolerated 560 mg ibrutinib for 6 cycles initially, then switched to a reduced dose of 420 mg for cycles 7 and 8 due to neutropenia. Brain MRIs have been stable with resolution of the small lymphoma residue after 6 cycles of ibrutinib. The patient continues ibrutinib for the goal of one year of consolidation therapy. DISCUSSION Our case highlights the potential of single-agent ibrutinib as consolidation therapy for PCNSL after HD-MTX and rituximab/temzolomide induction therapy.
Abstract 11079: Calcitonin Signaling Controls Disease-Induced Left Ventricular Remodeling
Authors: Abhijit R Takawale
Journal: Circulation (2021)

Introduction: We recently discovered that the well-known thyroid hormone calcitonin (CT) is produced by atrialcardiomyocytes (CMs) and regulates atrial fibrogenesis and arrhythmia susceptibility via CT receptors (CTRs) inatrial cardiofibroblasts (CFs). Whether the CT-CTR system regulates ventricular function and structure isunknown and was the object of this study. Method and Results: Human studies were performed on left ventricular (LV) samples from 27 patients who hadcardiac surgery (Oxford, UK; ethical approval 18/SC/0404). Animal studies used 8-10 week-old male control(CTR flx/flx ; n=150) and CTR -/- (n=131) mice subjected to transverse aortic constriction (TAC) and myocardialinfarction (MI), with selected analyses in wild type mice (n=5). Cardiac function was assessed byechocardiography at baseline, 3 and 6 weeks post-TAC, and 1 and 4 weeks post-MI.Expression profiling detected CTR and CT mRNA (qPCR; Fig. A-B) and protein (immunoblotting) in human LVtissue and mouse LV CMs and CFs, with a higher CT abundance in CMs. CTR protein was decreased in LV tissue from patients with hypertension vs non-hypertensive controls (Fig. C).CTR deletion enhanced atrial and LV fibrosis (Masson’s Trichrome; Fig. D-E), significantly exacerbated post-TAC LV ejection fraction reduction by 15.2% (Fig. F), and atrial (by 23.7%, Fig. G) and LV dilation (by 19.9%),while increasing induced-AF duration by 6-fold (Fig. H) and inducibility by 15% vs post-TAC controls.In CTR -/- mice, acute MI produced greater fibrosis in the LV risk-region (by 18%; Fig. I), ejection fractionreduction (by 14%, Fig. J) vs CTR flx/flx controls. Mortality, atrial dilation and AF-inducibility were similar inCTR -/- and control MI-mice. Conclusion: CTR deletion in mice exacerbates adverse LV remodeling and dysfunction in clinically-relevantdisease models, pointing towards an important protective role of CT-CTR signaling in ventricular myocardium.
Abstract 12600: Racial and Ethnic Disparities in the Management of Acute Myocardial Infarction Complicated by Cardiogenic Shock
Authors: Aditi Shankar, Sri Harsha Patolla, Pranathi R Sundaragiri, Saraschandra Vallabhajosyula
Journal: Circulation (2021)

Background: We sought to evaluate the impact of race/ethnicity on the in-hospital outcomes of acute myocardial infarction-cardiogenic shock (AMI-CS) in contemporary practice. Methods: This is a retrospective cohort study of AMI-CS admissions from the National inpatient Sample (2012-2017). Race was classified as White, Black and, Others (Hispanic, Asian/Pacific Islander, Native Americans). The primary outcome was in-hospital mortality, and secondary outcomes included use of invasive cardiac procedures, length of hospital stay and discharge disposition. Multivariate logistic regression and univariate analysis were used to analyze trends and outcomes. Results: We identified 203,905 (5.8%) AMI-CS admissions, of which 70.4% were White, 8.1% were Black and 15.7% of Other race. Black admissions were more often female, with lower socio-economic status, had higher comorbidities, and higher rates of non-ST-segment-elevation AMI-CS, cardiac arrest, and multi-organ failure. Black and Other races had lower rates of coronary angiography (69.3% vs 73.6% vs 75.3%), percutaneous coronary intervention (48.6% vs 54.8% vs 52.7%), coronary artery bypass grafting (15.1% vs 16.6% vs 19.7%) and mechanical circulatory devices (42.8% vs 43.7% vs 48.3%) compared to White races (all p &lt;0.001). Unadjusted in-hospital mortality was comparable for White (33.3%) and Black (33.8%) and lower for Other race (32.1%). After multivariable regression, the mortality for Black (odds ratio [OR] 0.85 [95% confidence interval {CI} 0.82-0.88]; p &lt;0.001) and Other race (OR 0.97 [95% CI 0.94-1.00]; p= 0.02) was lower than White race. Admissions of Black race had longer hospital stay, and lower rates of discharges to home. Conclusion: Contrary to previous studies, this contemporary study of racial disparities in AMI-CS noted Black and Other races had lower in-hospital mortality despite lower rates of cardiac procedures compared to White admissions.
Abstract 14232: Performance Of Cardiac Magnetic Resonance Fingerprinting Mapping - Evaluation By Comparison With Standard Techniques In A Large Patient Population
Authors: Varun Rajagopalan, Shruti Siva Kumar, Anant Madabhushi, Sadeer Al-Kindi, Jonathan R Walker, Jesse Hamilton, Nicole Seiberlich, Imran Rashid, Sanjay Rajagopalan
Journal: Circulation (2021)

Background: Parametric mapping is now widely used as a part of cardiac MRI protocols. Cardiac Magnetic Resonance Fingerprinting (cMRF) techniques for parametric mapping allow for simultaneous evaluation of T1 and T2 within a single acquisition. In this study, we evaluate the performance of cMRF through comparison with clinically utilized pulse sequences for T1 and T2 in a large heterogeneous population. Hypothesis: cMRF T1 and T2 measurements agree with clinically available mapping sequences in a heterogeneous patient cohort. Methods: We obtained myocardial T1 and T2 values across the whole mid short axis slice of the left ventricle in 175 patients using cMRF (T1/T2), Modified Look-Locker Inversion Recovery (MOLLI, T1), and T 2 -prepared balanced steady-state free precession (bSSFP). Patients were classified into the groups “Ischemic cardiomyopathy (ICM)”, “Nonischemic Cardiomyopathy (NICM)”, “Normal”, and “Other”. The group classified as “Other” was not analyzed separately. Results: cMRF had similar T1 compared with MOLLI (1036 vs 1046 ms, p=0.06, r=0.76) and slightly lower T2 compared with bSSFP (46.1 vs 49.6 ms, p&lt;0.01, r=0.5) in the entire cohort. Mean T1 was higher in ICM compared to Normal when measured by both MRF (1074 vs 997, p&lt;0.01) and MOLLI (1073 vs 1015, p&lt;0.01). The same was true when comparing NICM and Normal for both MRF and MOLLI (p&lt;0.01). T1 was more concordant in NICM (r=0.82) vs ICM (r=0.46) and Normal (r=0.54) while T2 had similar concordance across the spectrum of pathologies. Bland-Altman plots showed good agreement between cMRF and MOLLI (Bias: -9.86, 95% CI: -98.58, 78.86)/bSSFP (Bias: -3.55, 95% CI: -11.68, 4.57). The concordance was stable across a range of heart rates. Conclusions: cMRF is an emerging technique for simultaneous T1/T2 mapping in the myocardium. In a large heterogeneous population, cMRF T1 and T2 values showed good agreement with clinically-utilized pulse sequences. Further work is needed to identify sources of discrepancies.
NCOG-27. STATUS AS A CLINICAL TRIAL PARTICIPANT AND OUTCOME IN IDH-WILDTYPE GLIOBLASTOMA
Authors: Peter Pan, Adela Joanta-Gomez, Fabio Iwamoto, Mary Welch, Aya Haggiagi, Laura Donovan, Marissa Barbaro, Carlen Yuen, Andrew Lassman
Journal: Neuro-Oncology (2021)

Abstract INTRODUCTION Standard of care for glioblastoma consists of surgery, followed by combined chemoradiation and adjuvant chemotherapy, as per the seminal EORTC study from 2005. Clinical trial patients, being a population selected for functional status, hepatic function, renal function, and lack of other malignancies, may have improved outcome over the general treated population. METHOD Single center retrospective analysis of status as a clinical trial patient in the upfront setting and other clinical factors/biomarkers, analyzed for correlation with outcomes (PFS/OS) in IDH-wildtype glioblastomas. RESULTS 82 patients with IDH-wildtype glioblastoma were identified between 2014 and 2020, treated with standard of care or with an upfront clinical study (43% women; median age 66 years, range 35-91 years of age). 22 patients (27%) were treated with upfront clinical study. Status as a patient treated in an upfront clinical study did not correlate with outcome (hazard ratio HR PFS 0.99, CI 0.57-1.7, p=0.97; HR OS 1.09, CI 0.56-2.1, p=0.81). Frontal lobe was most frequently involved (n=36, 44%), followed by parietal lobe (n=33, 40%). Age was not a strong predictor of survival (R2 0.01). No statistically significant correlation was observed between outcome and laterality or location. MGMT promoter methylation was associated with improved PFS (HR 0.56, CI 0.33-0.94, p=0.03) and OS (HR 0.40, CI 0.19-0.85, p=0.02), with mPFS 6 months vs 9 months and mOS 16 months vs 20 months (unmethylated vs methylated respectively). CONCLUSION In this retrospective cohort of IDH-wildtype glioblastomas, age, tumor laterality, and tumor location were not significant predictors of outcome. MGMT promoter methylation predicted for superior PFS/OS. Patient selection for clinical studies are influenced by entry criteria, however at least in this retrospective review, status as a clinical study patient in the upfront setting did not correlate with outcome compared to patients treated with upfront standard of care.
Abstract 14219: White Cell Inflammatory Biomarkers in Women With Myocardial Infarction With Non-Obstructive Coronary Artery Disease (MINOCA): Findings From the American Heart Association Go Red for Women Strategically Focused Research Network
Authors: Jeffrey S Berger, Khrystyna Myndzar, Tessa A Barrett, Yuhe Xia, Nathaniel Smilowitz, Anais Hausvater, Sripal Bangalore, Louai Razzouk, Binita Shah, Tanya Spruill, Judith S Hochman, Harmony Reynolds
Journal: Circulation (2021)

Introduction: Myocardial infarction (MI) with non-obstructive coronary artery disease (MINOCA) occurs in 5-20% of women with MI. Underlying mechanisms of MINOCA are incompletely understood. Complete blood count (CBC) quantifies circulating cell types and can shed mechanistic insight into disease pathogenesis.. Methods: Peripheral blood was collected from women with MINOCA (n = 50; median 64 years [IQR 51-69]) and MI with coronary artery disease (MI-CAD; n = 71; 61 years [55-70]). Controls were women referred for elective cardiac catheterization found not to have obstructive CAD (n = 65; 62 years [57-69]). Blood was analyzed at the time of catheterization and in a subset of participants after 2 months. Associations between CBC parameters and MI subtype were estimated by multivariable logistic regression. Results: Overall, women with MI had higher WBC (p=0.008), monocyte counts (p&lt;0.001), neutrophil counts (p=0.001), monocyte:lymphocyte ratio (p&lt;0.001), and neutrophil:lymphocyte ratio (p&lt;0.001) than controls. No significant difference was noted for lymphocyte count, hemoglobin, platelet count and platelet size. When comparing MINOCA versus MI-CAD, there was no significant difference in age, race/ethnicity, diabetes, hypertension, and peak troponin. Women with MINOCA had lower WBC and neutrophil counts than MI-CAD at the time of MI. Compared to controls, women with MINOCA had higher monocyte counts, monocyte:lymphocyte ratio, and neutrophil:lymphocyte ratio. After adjustment for demographics, hypertension, hyperlipidemia, and diabetes, only monocyte count (β 0.22, p=0.04) and monocyte:lymphocyte ratio (β 0.32, p=0.005) were significantly associated with MINOCA (versus controls). Among 13 women with MI-CAD and 15 with MINOCA who had blood analyzed 2 months post their MI, monocyte count and monocyte:lymphocyte ratio decreased in the MI-CAD group, but did not decrease in the MINOCA group. Controls: In contrast leukocytosis across all white cell types in MI-CAD, women with MINOCA have a higher monocyte count and monocyte:lymphocyte ratio than controls. These parameters remained elevated over time in a pattern different from MI-CAD, suggesting a mechanistic role of monocytes in the pathogenesis of MINOCA.
Abstract MP215: Endothelial Colony Forming Cell Derived Exosomes Promote Angiogenesis And Cardiac Repair Post Myocardial Infarction
Authors: Karina P Gomes, Anshul S Jadli, Ananya Parasor, Noura N Ballasy, Monica Surti, Darrell D Belke, Methsala Wijesuriya, Paul W Fedak, Vaibhav B Patel
Journal: Circulation Research (2021)

Background: Despite improvements in therapeutics, ischemic heart disease remains a leading cause of death. Cardiac remodeling after myocardial infarction (MI), predominantly due to loss of cardiomyocytes and coronary vasculature, leads to a progressive decline in cardiac function resulting in heart failure. Current therapies for cardiac repair and heart failure are of limited benefit. Cell transplantation therapy upon MI is a very promising therapeutic strategy to replace dead myocardium, reducing scarring and improving cardiac performance. Methods and Results: Our research focuses on endothelial colony-forming cell-derived exosomes (ECFC-exosomes), which are actively secreted endocytic nanovesicles (30-100 nm) that transport functional miRNAs, proteins, mRNAs, and lipids, playing a key role in paracrine intercellular communication. We identified a novel ability of ECFC-exosomes to promote angiogenesis and cardiac tissue repair. Administration of ECFCs to mice following experimental end-organ ischemia resulted in ECFC-exosome-dependent increase in angiogenesis. ECFC-derived exosomes were taken up by endothelial cells leading to their proliferation and migration, tube formation, and formation of new vessels. Administration of ECFC-exosome to a murine model of MI prevented cardiac remodeling and heart failure. The acute MI resulted in severely decreased left ventricle ejection fraction (Sham 71.2% ± 5 .87, MI+Saline 32.9% ± 2.32) and fractional shortening (Sham 29.5% ± 3.20, MI+Saline 13.6% ± 2.87), and the administration of ECFC-exosomes prevented MI-induced cardiac dysfunction (ejection fraction: MI+ECFC-Exo 64.3% ± 8.74; fractional shortening: MI+ECFC-Exo: 26.4% ± 3.13). Next generation sequencing and bioinformatics analyses identified 136 miRNAs present in ECFC-exosome cargo, and factor inhibiting HIF-1α and PTEN as their potential targets in endothelial cells. Increased nuclear HIF-1α levels in response to ECFC-exosome administration, which may aid in the transcriptional function of HIF-1α, corroborated the role of exosomal miRNA in myocardial angiogenesis. We also found decreased levels of PTEN in response to ECFC-exosome treatment, which is a key negative regulator of PI3K/Akt pathways, survival pathways of heart. We also identified the relative angiogenesis expression profile of the peri-infarcted area in response to ECFC-exosome treatment. The ECFC-exosome administration upregulated the levels of VEGF, IGFBP-1 and PDGF, among others proangiogenic factors, and downregulated the levels of angiostatic factors as IP-10 and Thrombospondin-2. Conclusion: Our findings support the view that the ECFC-exosomes represent a novel therapeutic approach to improve cardiac repair after MI.
Abstract 13968: A Hybrid Convolutional and Recurrent Neural Network Architecture Accurately Detects Patients With Mitral Valve Prolapse From Echocardiography
Authors: Shinichi Goto, Francesca N Delling, Rahul C Deo
Journal: Circulation (2019)

Introduction: Computer vision approaches have enabled automation of multiple aspects of echocardiogram (echo) interpretation. However, neural network (NN) models applied to echo have focused on sti...
INNV-35. A MULTI-DISCIPLINARY REVIEW OF NEWLY DIAGNOSED HIGH GRADE GLIOMA REFERRALS TO THERAPIES, AND IMPLEMENTATION OF A SCREENING TOOL TO IMPROVE ACCESS TO THERAPIES AT THE ROYAL MARSDEN HOSPITAL (RMH)
Authors: Joanne Jethwa, Charmaine Jagger, Leanne Williams, Lizzy Jenkins, Kate Ashforth
Journal: Neuro-Oncology (2021)

Abstract Brain tumours make up 3% of all cancers. The disease and treatment have significant impact on function and quality of life (QoL). Early outpatient rehabilitation can improve function. National Institute of Clinical Excellence recommends patients have access to rehabilitation across the pathway, but unmet need is prevalent in this population. We recognised late referrals in our Trust and poor patient awareness of Therapies, resulting in reduced access to rehabilitation. METHOD: A retrospective notes review of new neuro-oncology patients (n=56) referred to RMH from July - December 2018 was undertaken to identify therapy needs and timeliness of referrals. A therapy screening tool was devised and piloted from July – December 2019. Additionally, an MDT questionnaire was circulated to gain feedback regarding this service. RESULTS: Retrospective review revealed that of those patients with identified therapy needs, 16% of physiotherapy (PT), 10% of Occupational Therapy (OT) and 9% of Speech and Language Therapy (SLT) were referred late. Additionally, referrals were not received for 40% of patients with OT needs, 32% for PT and 30% for SLT. Following implementation of the screening tool, referrals occurred earlier in the pathway, and rates increased by 60% in SLT, 59% in PT, and 25% in OT. An MDT questionnaire revealed 100% consensus that screening was beneficial to patients and the MDT with improved access to therapies. CONCLUSION: Brain tumour patients require prompt therapy intervention to improve and maintain function and QoL. We identified high levels of unmet need which was eliminated by a screening tool and subsequently increased referral rates. Patients and the MDT had improved awareness of the role of Therapies, as well as earlier access. The neuro-oncology MDT benefitted from the effects of therapy intervention improving patient tolerance to oncological treatment. Therapists were able to identify and manage impairments earlier, improving QoL.