tbuckley/cabot-search huggingface dataset:
NIMG-57. MANAGEMENT OF TECTAL GLIOMAS IN ADULTS
Authors: Ramya Tadipatri, Dinko Plasto, Jeremy Hughes, Peter Nakaji, Jennifer Eschbacher, Ekokobe Fonkem, Amir Azadi, Kelly Braun, Charlotte Myers, Lynn Ashby
Journal: Neuro-Oncology (2021)

Abstract BACKGROUND Tectal gliomas (TG) are rare tumors occurring primarily in children but also found in adults during workup of various neurological symptoms. Surgery is not required in asymptomatic cases, so histopathological information is sparse. No consensus on timing of imaging surveillance or management has been established. OBJECTIVE We seek to standardize neuroimaging, including MRI protocol and surveillance time intervals, and clinical management of symptoms and disease progression, including surgery, radiotherapy, and chemotherapy. METHODS At our institution, patients with TG were identified through a search of radiology reports and clinic notes between 1989 and 2020. Initial and serial MRI exams were evaluated for tumor size, enhancement, edema, hydrocephalus, and other radiographic features. When tissue was available, cellularity, mitotic activity, and morphology were described. We documented neurological symptoms and signs potentially related to the tumor. RESULTS 37 cases were identified: 22 female, 15 male; 5 children, 32 adults. Age of diagnosis ranged from 7 to 69 years. Presenting symptoms included headache (59%), visual symptoms (35%), and imbalance (14%), less commonly: seizure, weakness, nausea/vomiting, and dizziness. Surgical procedures included biopsy (9), resection (7), endoscopic third ventriculostomy (15), and shunt placement (11). Eight patients received radiotherapy, including IMRT, CyberKnife, GammaKnife, and Zap-X (all adults; 4 at diagnosis, 3 at progression, 1 at diagnosis and again at progression). Four patients received chemotherapy (all adults; 1 at diagnosis, 3 at progression), all with temozolomide. One additionally received bevacizumab for radionecrosis. Three patients died with progressive disease, two following treatment and one without. Of interest, 5 adult patients developed signs of parkinsonism during their follow-up period. CONCLUSION Management of TG encompasses both neoplastic progression and symptom control, either from local compression or infiltrative disease. We have developed an algorithm for imaging surveillance and treatment, including MRI protocol, definition of progressive disease, and indications for antineoplastic therapies.
Abstract 10493: Prognostic Value of Right Ventricular Longitudinal Strain in Transthyretin Amyloid Cardiomyopathy
Authors: Hiroki Usuku, Seiji Takashio, Eiichiro Yamamoto, Toshihiro Yamada, Fumi Oike, Koichiro Fujisue, Daisuke Sueta, Kenichi Matsushita, Kenichi Tsujita
Journal: Circulation (2021)

Introduction: This study was performed to investigate whether right ventricular global longitudinal strain (RV-GLS) provides prognostic information in patients with wild-type transthyretin amyloid cardiomyopathy (ATTRwt-CM). Methods and Results: Among 129 patients who were diagnosed with ATTRwt-CM at Kumamoto University Hospital from December 2002 to December 2019, 111 patients who had enough information for two-dimensional speckle tracking imaging were retrospectively analyzed in this study. During a median follow-up of 615 days (25 th -75 th percentile; 318-1082 days), 26 cardiovascular deaths occurred. Compared with patients in the non-event group, those in the cardiovascular death group had significantly lower RV-GLS (10.9±2.7% vs. 12.8±3.5%, p&lt;0.05) and right ventricular free wall longitudinal strain (13.1±3.3% vs. 15.5±3.8%, p&lt;0.01). However, conventional echocardiographic findings, such as left ventricular ejection fraction and E/e’ ratio were not significantly different between these two groups. Receiver operating characteristic analysis showed that the area under the curve of RV-GLS for cardiovascular death was 0.668 and that the best cutoff value of RV-GLS was 11.59% (sensitivity 69.2%; specificity, 63.5%). In the Kaplan-Meier analysis, patients with ATTRwt-CM who had low RV-GLS (&lt;11.59%) had a significantly higher probability of total cardiovascular death (p&lt;0.01). After adjusting for conventional predictive factors (age, history of heart failure, hs-cTnT, and B-type natriuretic peptide), low RV-GLS was significantly and independently associated with cardiovascular death in patients with ATTRwt-CM (odds ratio, 3.40; 95% confidence interval, 1.26-9.18; p&lt;0.05). Conclusions: RV-GLS has significant prognostic value in patients with ATTRwt-CM and provides greater prognostic power than conventional echocardiographic parameters.
Abstract 12380: 1,5-anhydroglucitol is a Novel and Independent Predictor of Mortality in Patients With COVID-19
Authors: Eric Button, Hirotaka Ishibashi, Kevin Bliden, Elizabeth Clark, Stewart Holt, Arvind Singh, Udaya Tantry, Jeffrey Dahlen, Paul A Gurbel
Journal: Circulation (2021)

Background: Fasting hyperglycemia and diabetes are the independent predictors of morbidity and mortality in patients with COVID-19. Glycemic fluctuations may be independently associated with poor prognosis in adult patients hospitalized for COVID-19. Hypothesis: We hypothesize that 1,5-anhydroglucitol (1,5-AG), a marker of glycemic variability, is strongly associated with in-hospital mortality in patients with COVID-19. Methods: Medical history, demographic variables, and laboratory measurements were collected within 48 hours of hospitalization in COVID-19 patients (n=64), including 9 patients who died in the hospital. Serum 1,5AG was measured by an enzymatic colorimetric assay (GlycoMark, Precision Diabetes, Inc. Raleigh, NC). Multivariate regression analysis was performed to assess the relation between fasting glucose, hemoglobin (Hb)A1c and 1,5-AG and mortality. Results: Baseline mean ± SD for fasting blood glucose,1,5-AG and HbA1c (available in 40 patients) were 143 ± 69 mg/dL and 14.7 ± 8.8 ug/mL and 6.9±2.3%, respectively. Only 1,5-AG was an independent predictor of mortality (n=64, AUC = 0.69, p=0.017), but not fasting glucose (n=64, AUC =0.60, p=0.32) or HbA1c (n=40, AUC=0.58, p =0.46), respectively. With respect to clinical variables, a combination of BMI and Age was predictive of mortality (AUC = 0.77, p=0.004). Interestingly, when 1,5-AG was added to BMI and Age, the AUC increased to 0.94 (p &lt;0.0001). When fasting glucose was added to BMI and Age the AUC was 0.79 (p =0.001). A cox regression analysis demonstrated that 1,5-AG &lt; 10 ug/mL was associated with an odds ratio of 0.44 (95% CI =0.11-1.85) for mortality. Conclusions: This analysis demonstrated that 1,5-AG is a novel and independent predictor of COVID-19 mortality. 1,5-AG may provide important and unique information in the COVID-19 clinical setting. An algorithm of BMI, Age, and 1,5-AG can be used clinically to predict mortality. These findings warrant further investigation in larger studies specific for diabetic and non-diabetic populations.
The Use of Ibrutinib in Italian CLL Patients Treated in a Real-World Setting (EVIDENCE): A Preliminary Report
Authors: Stefano Molica, Potito Rosario Scalzulli, Lydia Scarfo, Attilio Guarini, Roberta Murru, Paolo Sportoletti, Ferdinando Frigeri, Francesco Albano, Nicola Di Renzo, Alessandro Sanna, Idanna Innocenti, Massimo Massaia, Marta Coscia, Elsa Pennese, Caterina Patti, Gianluigi Reda, Agostino Tafuri, Anna Grugnetti, Valeria Magarotto, Francesca Romana Mauro
Journal: Blood (2021)
Response to: Correspondence on ‘No efficacy of anti-IL-23 therapy for axial spondyloarthritis in randomised controlled trials but in post-hoc analyses of psoriatic arthritis-related ‘physicianreported spondylitis’?’ by Siebert and Marzo-Ortega
Authors: Juergen Braun, Robert BM Landewé
Journal: Annals of the Rheumatic Diseases (2021)

With great interest, we read the comment of our colleagues from the UK on our recent viewpoint,1 and we appreciate that they largely agree with us.2 This is a bit different in a recent review on the same topic,3 which argues that it is still possible that anti-IL23 agents work for axial psoriatic arthritis (PsA). Nevertheless, our colleagues from the UK raise two important points, which we like to shortly comment on.

First, the important factor of age is discussed, which plays an important role in the frequent clinical situation of patients presenting to the doctor because of acute or chronic back pain—simply because the prevalence of degenerative changes in the axial skeleton does increase with age,4 5 and axial spondyloarthritis (axSpA) starts most often in the third decade of life6 …
Abstract 13547: Secondary Prevention of Rheumatic Heart Disease in Ethiopia
Authors: Wubishet Belay, Azene Dessie, Hayat Ali, Etsegenet Gedlu, Abinet M Walle, Abdulkadir Buser, Zemene Tigabu, Muktar H Aliyu, Jonathan Soslow
Journal: Circulation (2021)

Introduction: Acute rheumatic fever (ARF) and rheumatic heart disease (RHD) are significant causes of morbidity and mortality. Ethiopia has a high RHD prevalence but has no national strategic guidelines for preventing RHD and no data on the status of secondary prevention in children with RHD. Generating local information is essential to designing effective prevention and control strategies. This study describes the status of secondary RHD prevention in Ethiopian children. Methods: A multicenter, cross-sectional study was performed in children aged 5-17 years with an echocardiogram-based RHD diagnosis. Participants with congenital heart disease and a recent RHD diagnosis (&lt;1 year) were excluded. Good adherence was defined as at least 80% completion of intramuscular benzathine penicillin (BPG) or oral Amoxicillin within the previous year. The primary outcome measure was adherence to prophylaxis, expressed as a proportion. Covariates included socio-demographics, type and severity of RHD, and ARF recurrence. Chi-square test and Student’s t-test were used to assess differences. Multivariate logistic regression was performed. Results: We included 337 participants with a mean age (±standard deviation) of 12.9±2.6 years. The majority were females (54%) and 73% had severe aortic/mitral disease. BPG (80%) and Amoxicillin (20%) were the prophylaxis of choice. Predictors of good adherence were female sex (P=0.04), use of BPG (0.03), and shorter mean duration of prophylaxis in months (48.5±31.5 vs. 60.7±33, P&lt;0.008). Running out of medicines (35%), interrupted follow-up (27%), and the COVID pandemic (26%) were the three most common reasons for missing prophylaxis. Recurrence of ARF was higher in participants on Amoxicillin (40% vs. 16%, P&lt;0.001) and in those with poor adherence (36.8% vs. 17.9%, P=0.005). Type and duration of prophylaxis (OR 0.5, P =0.02; OR=1.1, P =0.04, respectively), and sex (OR=1.9, P =0.03) were independent predictors of poor adherence. Conclusion: Poor adherence is prevalent in Ethiopian children with RHD. Amoxicillin is a suboptimal option for prophylaxis associated with lower adherence and a higher rate of ARF recurrence.
Laboratory Characterization of Unclassified Bleeding Disorders By Non-Conventional Tests
Authors: Paula Acuña, Elena Monzón Manzano, Elena G Arias-Salgado, María Teresa Alvarez Román, Mónica Martín, María Isabel Rivas Pollmar, Víctor Jiménez-Yuste, Miguel Canales, Nora V. Butta
Journal: Blood (2021)
Transcriptional Profile Investigation Identified Aberrant <i>CD34</i> Isoforms and <i>Apela</i> As a Hub Gene in <i>IGH-DUX4</i> Subtype B-Cell Precursor Acute Lymphoblastic Leukemia
Authors: Guangsi Zhang, Panxiang Cao, Fang Wang, Xue Chen, Yang Zhang, Mingyu Wang, Daijing Nie, Xiaoli Ma, Ming Liu, Hongxing Liu
Journal: Blood (2021)
CTNI-20. FEASIBILITY OF SINGLE-PASS STEREOTACTIC NEEDLE BIOPSY IN RECURRENT GLIOBLASTOMA PATIENTS TO SUPPORT CLIA-CERTIFIED TUMOR PHARMACODYNAMICS FOR A PHASE 0/2 CLINICAL TRIAL
Authors: Yu-Wei Chang, Anita DeSantis, Chelsea Pennington-Krygier, Jennifer Molloy, Shwetal Mehta, Nader Sanai, An-Chi Tien
Journal: Neuro-Oncology (2021)

Abstract BACKGROUND In neuro-oncology clinical trials, pharmacodynamic (PD) analysis of tumor tissue before and after experimental therapy is challenging. Today, Phase 0 studies in brain tumor patients typically employ archival tissue from a prior resection as the baseline PD comparator. However, the time-interval between tissue acquisitions can be months to years and often includes confounding exposure to other therapies. Here, we demonstrate the feasibility of a pre-treatment, single-pass stereotactic needle biopsy to support CLIA-certified genetic screening and tumor PD analysis in a Phase 0/2 clinical trial. METHODS In support of an ongoing Phase 0/2 ‘trigger’ trial testing CDK4/6 plus ERK1/2 inhibition in recurrent glioblastoma (GBM), a single-pass stereotactic biopsy was completed in select patients prior to enrollment. Each biopsy yields six tissue cores for immunohistochemistry (IHC) and genetic characterization. Using CLIA-certified protocols, genomic DNA (gDNA) was extracted from two cores, followed by library preparation and next-generation sequencing of a customized panel of 37 genes (IvySeq). In the four remaining cores, IHC staining was performed for RB, pRB, pERK, pS6, CDKN2A, MIB-1, ClCas-3 and pH2AX. RESULTS Single-pass stereotactic needle biopsies were collected from five recurrent GBM patients. No intraoperative, perioperative, or radiographic evidence of morbidity was observed. 800-2400ng of gDNA was isolated from each stereotactic biopsy. IvySeq analysis detected CDKN2A deletion, ATRX loss, and mutations in IDH, PTEN and TP53 genes. Based on IHC and genetic analyses of the biopsied samples, three patients were enrolled into the Phase 0/2 clinical trial and baseline value were used for PD analysis. CONCLUSION Single-pass stereotactic needle biopsy is a feasible and safe strategy to collect pre-treatment tissue in support of a Phase 0 clinical trial, enabling CLIA-certified genetic analysis for trial screening and tumor PD analysis.
Key use cases for artificial intelligence to reduce the frequency of adverse drug events: a scoping review
Authors: Ania Syrowatka, Wenyu Song, Mary G Amato, Dinah Foer, Heba Edrees, Zoe Co, Masha Kuznetsova, Sevan Dulgarian, Diane L Seger, Aurélien Simona, Paul A Bain, Gretchen Purcell Jackson, Kyu Rhee, David W Bates
Journal: The Lancet Digital Health (2021)

Adverse drug events (ADEs) represent one of the most prevalent types of health-care-related harm, and there is substantial room for improvement in the way that they are currently predicted and detected. We conducted a scoping review to identify key use cases in which artificial intelligence (AI) could be leveraged to reduce the frequency of ADEs. We focused on modern machine learning techniques and natural language processing. 78 articles were included in the scoping review. Studies were heterogeneous and applied various AI techniques covering a wide range of medications and ADEs. We identified several key use cases in which AI could contribute to reducing the frequency and consequences of ADEs, through prediction to prevent ADEs and early detection to mitigate the effects. Most studies (73 [94%] of 78) assessed technical algorithm performance, and few studies evaluated the use of AI in clinical settings. Most articles (58 [74%] of 78) were published within the past 5 years, highlighting an emerging area of study. Availability of new types of data, such as genetic information, and access to unstructured clinical notes might further advance the field.
Igh-V(D)J NGS-MRD Measurement in Pediatric B-Acute Lymphoblastic Leukemia
Authors: Suying Lu, Jia Zhu, Junting Huang, Juan Wang, Feifei Sun, Zijun Zhen, Xiangjing Hu, Chao Song, M. James You, Xiaofei Sun, Yi Que, Lian Zhang, Yizhuo Zhang
Journal: Blood (2021)
NIMG-65. RESTING-STATE FUNCTIONAL MRI DEMONSTRATES DAMAGE TO FUNCTIONAL CONNECTIVITY IN MENINGIOMA PATIENTS WITH PERIFOCAL EDEMA
Authors: Veit Stoecklein, Stephan Wunderlich, Boris Papzov, Hesheng Liu, Michael Schmutzer, Niklas Thon, Christian Schichor, Jörg-Christian Tonn, Sophia Stoecklein
Journal: Neuro-Oncology (2021)

Abstract BACKGROUND Meningiomas are common intracranial tumors which usually carry a benign prognosis. Some meningiomas cause perifocal edema which might indicate that this subset could interfere with normal brain function. Resting-state functional MRI (rsfMRI) can be used to assess whole brain functional connectivity (fc) which can be used as a marker for disease severity in patients with intracranial tumors, as was recently shown by our group in a cohort of glioma patients. In this study, we investigated whether the presence of perifocal edema in preoperative patients with meningioma leads to fc. METHODS Patients with suspected meningioma were prospectively included and functional resting state MRI scans were obtained. The resulting data was processed according to our recently published method and abnormality of fc was quantified for each individual patient. Abnormality of fc was then correlated with tumor and edema volume as well as WHO grade. RESULTS 26 patients (23 WHO grade I, 3 WHO grade II) were included. 13 patients had perifocal edema. There was a highly significant correlation between edema volume and higher abnormality of fc both in the lesional and the contra-lesional hemisphere (r=0.51, p=0.008 and r=0.61, p=0.001). Patients with no perifocal edema showed only very low abnormality of fc. Tumor volume was not correlated with abnormal fc in both the lesional and the contralesional hemispheres (r=0.23, p=0.27 and r=0.28, p=0.17). There was also no significant correlation between WHO grade and abnormality of fc. CONCLUSION RsfMRI showed significant abnormal fc in meningioma patients with perifocal edema in contrast to patients without edema, independent of tumor volume. This demonstrates that the presence of edema but not the tumor volume is relevant for disturbances of fc.
Abstract 13436: Temporal Changes In Demographic Characteristics, Use Of Multimodal Imaging, And Treatments In Patients With Bicuspid Aortic Valves: Data From A Large Korean Registry
Authors: Kyu Kim, Dae-Young Kim, Jiwon Seo, Iksung Cho, Geu-Ru Hong, Jong-Won Ha, CHI YOUNG Shim
Journal: Circulation (2021)

Introduction: We aimed to investigate the temporal changes in demographic characteristics, use of multimodal imaging, and treatments in patients with bicuspid aortic valves from a large Korean registry. Methods: A total of 1,514 patients (mean 71.5%, 56 ±14 years old) who were first diagnosed with BAV from Jan 2003 through Dec 2020 in a single tertiary referral center in Korea were investigated. They were divided into 3 groups according to the year of diagnosis: group 1 (2003-2008, n=270), group 2 (2009-2014, n=590), and group 3 (2015-2020, n=654). Significant aortic stenosis (AS) was defined as at least moderate AS and significant aortic regurgitation (AR) was defined as at least moderate AR based on the current guideline. Non-dysfunctional BAV was defined as BAV without significant AR or AR. Presence of aortopathy was defined as any portions of ascending aorta ≥ 45 mm. Use of imaging for diagnosis and the treatment method were comprehensively investigated. Results: Both age at diagnosis [55 (interquartile range [IQR], 44 to 60) in Group 1, 59 (48 to 67) in Group 2, 60 (60 to 68) in Group 3, p for trend &lt;0.001] and surgery [56 (46 to 64), 60 (52 to 69), 62 (56 to 69), p for trend &lt;0.001] showed increasing trend. Non dysfunctional BAV had increased (25.2%, 36.3%, and 33.9%, p=0.005). The frequency of IE as an initial presentation significantly decreased as time passes (4.8%, 2.9%, and 1.7%, p&lt;0.008). The incidences of aortopathy were not significantly different among three temporal groups. The use of multimodal imaging (concomitant use of computed tomography and transesophageal echocardiography) had significantly increased (1.5%, 6.8%, 19.3%), p&lt;0.001]. There was also increasing trend in transcatheter aortic valve replacement (2.2% in group 2; 4.5% in group 3, p&lt;0.001] Conclusions: In the past 18 years, there were remarkable temporal changes in patients’ demographic characteristics, use of multimodal imaging for diagnosis, complications and treatment in patients with BAV.
Abstract 12302: Na <sub>V</sub> 1.6 Dysregulation by Mutant Calmodulin Enhances Late Sodium Current in Human iPSC Cardiomyocytes and Promotes Arrhythmias in D96V Calmodulin-Expressing Transgenic Mice
Authors: Mikhail Tarasov, yusuf olgar, Heather Struckman, Alec Miller, Jonathan Davis, Sandor Gyorke, Rengasayee Veeraraghavan, Przemyslaw Radwanski
Journal: Circulation (2021)

Calmodulin (CaM) mutants are associated with severe arrhythmias (calmodulinopathy). While dysregulation of Ca 2+ handling proteins (RyR2, Ca V 1.2) are known mediators of calmodulinopathy, the role of Na + channels (Na V s) remains unclear. Interestingly, effects on Ca V 1.2 do not fully explain action potential (AP) prolongation by the long QT syndrome CaM mutant D96V. We investigated Na V dysregulation by D96V-CaM and its arrhythmogenic impact. In wild-type (WT) murine cardiomyocytes (CM) dialysis of D96V-CaM (6.5 μM) via a patch pipette prolonged AP, induced early and delayed afterdepolarizations (EADs and DADs) and increased Ca 2+ waves compared to WT-CaM. The effects of D96V-CaM were abrogated by a Na V 1.6 blocker, 4,9-anhydrotetrodotoxin (4,9ahTTX, 300 nM; Fig. 1A ). Dialysis of D96V-CaM dysregulated inactivation of 4,9ahTTX-sensitive Na + current (I Na ) promoting late I Na in WT murine CM ( Fig. 1B ) and in Chinese Hamster Ovary (CHO) cells expressing Na V 1.6 but not Na V 1.5. D96V-CaM, but not WT-CaM, also promoted late I Na in human induced pluripotent stem cell (iPSC) - derived ventricular myocytes, underscoring translational relevance ( Fig. 1C ). To examine the arrhythmia potential of Na V 1.6 dysregulation by D96V-CaM, we generated mice with cardiac-specific expression of D96V-CaM (cD96V; tgD96V-CaM x β-MHC-Cre). cD96V mice exhibited increased late I Na and Ca 2+ waves resembling those in D96V-CaM-dialyzed WT CMs. In vivo cD96V mice evidenced prolonged QTc intervals and ventricular tachycardia (VT) during bradycardia (carbachol 0.5 mg/kg intraperitoneal). Cardiac-specific Na V 1.6 knockout protected cD96V mice from impaired I Na inactivation and arrhythmogenic Ca 2+ waves on cellular level as well as long QT and VT in vivo ( Fig. 1D, E ). In summary, D96V-CaM promotes arrhythmias by dysregulating Na V 1.6 and thereby, facilitating aberrant Ca 2+ release. Importantly, Na V 1.6 may be a therapeutic target for management of CaM-related arrhythmias.
Clinical Features and Survival According to Minimal Residual Disease in a Colombian Population Diagnosed with B-Cell Acute Lymphoblastic Leukemia
Authors: Angela María Peña, Sandra Vanesa Rios, Luis Antonio Salazar, Manuel Rosales, Sara Ines Jimenez, Katherinee Morales-Chacon, Carlos Alberto Orozco Oviedo, Carlos Andres Perez, Xueyi Chen, Santiago Grandas, Gabriela Vesga, Ana Maria Prada, Miguel Ochoa, Maria Luna-Gonzalez, Jose Sandoval-Sus, Claudia Lucia Sossa
Journal: Blood (2021)