tbuckley/cabot-search huggingface dataset:
Abstract 12190: The Role of Lipid Core Burden Index Measured by Near-Infrared Spectroscopy in Predicting Slow TIMI Flow After Coronary Intervention
Authors: Subin Lim, Jung-Joon Cha, Hyung Joon Joo, Jae Hyoung Park, Cheol Woong Yu, Tae Hoon Ahn, Do-Sun Lim, Soon Jun Hong
Journal: Circulation (2021)

Background: Decreased TIMI flow following percutaneous coronary intervention (PCI) is associated with poor clinical outcomes. However, predicting slow TIMI flow after PCI is limited. Herein, we investigated predicting slow TIMI flow based on the lipid core burden (LCB) of target lesion by using near-infrared spectroscopy-intravascular ultrasound (NIRS-IVUS). Methods and Results: This study retrospectively evaluated 636 patients who underwent NIRS-IVUS guided PCI from a single tertiary center registry. Total patients were divided into decreased TIMI flow group (n=90, TIMI 0, 1, and 2) and normal TIMI flow group (n=546, TIMI 3). The extent of LCB in the treatment zone was calculated as the maximal LCB index (maxLCBi) measured by NIRS for each of the 4-mm longitudinal segments in the treatment zone. In three-month composite events including all-cause death, myocardial infarction, stent thrombosis, and re-intervention, decreased TIMI flow group showed worse clinical outcomes compared to normal TIMI flow group (5.6% vs. 1.5%, log-rank p=0.010). To investigate the correlation between TIMI flow and lipid core burden, a receiver-operating characteristic analysis was performed, and a high LCBi group was defined as maxLCBi 4mm ≥353. Multivariate logistic regression analysis revealed that high LCBi group was strongly associated with decreased TIMI flow (OR 2.223, 95% CI 1.341-3.685, p=0.002). Conclusions: High LCBi measured by NIRS-IVUS could be considered an independent predictor for decreased TIMI flow. Furthermore, a high value for LCBi could lead to worse clinical outcomes.
Abstract 13635: Isolated Right Ventricular Stress Cardiomyopathy: A Systematic Review of Literature
Authors: Yesha P Rana, Vishal P Rana, Balaram J Hanumanthu, Pramod Theetha Kariyanna, Deepika Misra
Journal: Circulation (2021)

Background: Takotsubo Cardiomyopathy (TTC), also known as stress cardiomyopathy, is characterized by transient systolic and diastolic dysfunction without evidence of significant coronary artery stenosis. In 2012, TTC attributed to about 0.02% of hospitalizations in the United states, largely seen in the elderly female population. Although it primarily affects the left ventricle, there are different variant patterns documented mostly affecting younger individuals. Here we present a systematic review of right ventricle TTC. Methods: On January 7th, 20221, a systematic search without limitation in the time frame was conducted using Pubmed, Google Scholar, CINAHL, Cochrane CENTRAL, and Web of Science databases and a total of 9 cases were identified (1 case was excluded due to duplicity). Results: The mean age of the patients listed was 65.2 ± 23.35 with majority (8/9) 88% of patients being women. Commonest presentation was dyspnea (67%), followed by chest pain (22%), nonspecific discomfort in 11%, and acute heart failure in 11%. Cardiogenic shock was reported in 56% of the cases. Management and treatment included inotropic or vasopressor support in 67% of the cases and 11% requiring venoarterial extracorporeal membrane oxygenation (V-A ECMO). Improvement of right ventricular function was reported in all but 1 patient who died. Conclusion: Isolated right ventricular stress cardiomyopathy is rare but possibly underreported. Though associated with a higher incidence of cardiogenic shock on presentation than traditional stress cardiomyopathy, they do seem to spontaneously recover once out of the acute phase of the syndrome as noted in our study. While the pathogenesis of stress cardiomyopathy is still not fully understood, genetic predispositions may be involved. Current recommendations for management include conventional heart failure medications including beta blockers, ACE inhibitors and diuretics despite limited evidence.
Chromatin Accessibility Landscapes of Acute Lymphoblastic Leukemia
Authors: Kelly R. Barnett, Jonathan D. Diedrich, Brennan P. Bergeron, Wenjian Yang, Kristine R. Crews, Wendy Stock, Elisabeth M. Paietta, Steven M. Kornblau, Hiroto Inaba, Sima Jeha, Ching-Hon Pui, Mary V. Relling, William E. Evans, Jun J. Yang, Daniel Savic
Journal: Blood (2021)
NIMG-28. PROSPECTIVE HISTOPATHOLOGY-VALIDATED MACHINE LEARNING FOR DISTINGUISHING TRUE PROGRESSION FROM TREATMENT-RELATED CHANGES IN GLIOBLASTOMA PATIENTS
Authors: Hamed Akbari, Anahita Fathi Kazerooni, Spyridon Bakas, Chiharu Sako, Elizabeth Mamourian, Jeffrey D Rudie, Gaurav Shukla, Stephen J Bagley, Arati Desai, Steven Brem, Robert A Lustig, Ronald L Wolf, Michel Bilello, Donald M O’Rourke, Suyash Mohan, MacLean Nasrallah, Christos Davatzikos
Journal: Neuro-Oncology (2021)

Abstract PURPOSE Decision making about the best course of treatment for glioblastoma patients becomes challenging when a new enhancing lesion appears in the vicinity of the surgical bed on follow-up MRI (after maximal safe tumor resection and chemoradiation), raising concerns for tumor progression (TP). Literature indicates 30-50% of these new lesions describe primarily treatment-related changes (TRC). We hypothesize that quantitative analysis of specific and sensitive features extracted from multi-parametric MRI (mpMRI) via machine learning (ML) techniques may yield non-invasive imaging signatures that distinguish TP from TRC and facilitate better treatment personalization. METHODS We have generated an ML model on a retrospective cohort of 58 subjects, and prospectively evaluated on an independent cohort of 58 previously unseen patients who underwent second resection for suspicious recurrence and had availability of advanced mpMRI (T1, T1-Gd, T2, T2-FLAIR, DTI, DSC). The features selected by our retrospective model, representing principal components analysis of intensity distributions, morphological, statistical, and texture descriptors, were extracted from the mpMRI of the prospective cohort. Integration of these features revealed signatures distinguishing between TP, mixed response, and TRC. Independently, a board-certified neuropathologist evaluated the resected tissue by blindly classifying it in the above three categories, based on mitotic figures, pseudopalisading necrosis, geographic necrosis, dystrophic calcification, vascular changes, and Ki67. RESULTS Tissues classified as TRC by the neuropathologist were associated with imaging phenotypes of lower angiogenesis (DSC-derived features), lower cellularity (DTI-derived features), and higher water concentration (T2, T2-FLAIR features). Our ML model characterized TP with 78% accuracy (sensitivity:86%, specificity:70%, AUC:0.80 (95%CI, 0.68-0.92)) and TRC with 81% accuracy (sensitivity:80%, specificity:81%, AUC:0.87 (95%CI, 0.72-1.00)). CONCLUSION Our proposed ML model reveals distinct non-invasive markers of TP and TRC, directly associated with histopathological changes in prospective glioblastoma patients. Reliable stratification of TP and TRC entities may help to noninvasively determine whether the course of treatment should change.
Effect of 7 vs 14 Days of Antibiotics Among Afebrile Men With Urinary Tract Infection
Authors: Sunn Hoah Kelvin Yap
Journal: JAMA (2021)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Complete Remission with Devimistat (CPI-613) in Refractory Burkitt Lymphoma
Authors: Liana Nikolaenko, Timothy Pardee, Raphel Steiner, Jeremy S. Abramson, Steven M. Horwitz, Matthew J. Matasar, Colette Owens, Ildefonso Rodriguez-Rivera, David J. Straus, Sanjeev Luther, Ariela Noy
Journal: Blood (2021)
Abstract 14155: Exposure to sFlt1-Induced Preeclampsia Enhances the Future Vascular Response to Hypertensive Stimuli in Mice in a Smooth Muscle Mineralocorticoid Receptor Dependent Manner
Authors: Lauren Biwer, Qing Lu, Jaime Ibarrola Ulzurrun, Joshua Man, Brigett Carvajal, Zsuzsanna K Zsengeller, Ellen Seely, Ananth Karumanchi, Iris Z Jaffe
Journal: Circulation (2021)

Preeclampsia (PE), a syndrome of high blood pressure (BP) and renal damage in late pregnancy, is associated with increased soluble VEGF receptor (sFlt1) and survivors have increased risk of future hypertension with increased angiotensin II (AngII) and salt sensitivity. Since smooth muscle cell mineralocorticoid receptor (SMC-MR) can be activated by hypertensive stimuli, we hypothesized that high sFlt1 exposure during pregnancy may induce a post-partum state of enhanced vascular sensitivity via SMC-MR activation. A PE model was induced by transient viral expression of sFlt1 in pregnant C57Bl6 mice. Elevated serum sFlt1, BP and glomerular endotheliosis was confirmed which all resolve post-partum. Two months later, resistance arteries from post-PE mice show no change in vasoconstriction to AngII but with increased mRNA ratio of the pro-constrictive AngII receptor-1(ATR1) to the vasodilatory ATR2. In a small cohort of women with prior PE, we confirm salt sensitivity of BP thus, postpartum mice were implanted with telemetric BP monitors and exposed to high salt or AngII (600mg/kg/day) infusion. Mice with prior PE had a significantly increased BP response to hypertensive stimuli. Microvessels from mice after PE and hypertensive stimuli had enhanced ex vivo myogenic tone and AngII vasoconstriction. To test the direct impact of sFlt1 on SMC-MR function, cultured SMC (Pac1) were transiently exposed to sFlt1 (24 hours on then off) to mimic the post-PE state. SMC-MR transcriptional activity in response to aldosterone and AngII were significantly increased after sFlt1 exposure as measured by luciferase reporter assay. SMC-MR activation and target gene expression was also enhanced after sFlt1 exposure (including AT1R/AT2R ratio). Finally, the role of SMC-MR in the post-PE phenotype was tested in vivo by PE induction in SMC-MR-KO vs MR-intact littermates. Post partum, SMC-MR-KO mice were protected from the PE-induced increase in aortic stiffness, microvascular myogenic tone and AngII vasoconstriction. sFlt1-induced PE produces a state of enhanced sensitivity to AngII that may be mediated by increased activation of SMC-MR. These data support the use of MR antagonists to mitigate the increased risk of cardiovascular disease in women exposed to PE.
Abstract MP201: PKA Regulatory Subunit 1α As A Novel Necrosis Suppressor In Myocardial Ischemia/Reperfusion
Authors: Yuening Liu, Jingrui Chen, Peng Xia, Constantine A Stratakis, Zhaokang Cheng
Journal: Circulation Research (2021)

Reperfusion therapy, the standard treatment for acute myocardial infarction, can trigger necrotic death of cardiomyocytes and provoke ischemia/reperfusion (I/R) injury. However, signaling pathways that regulate cardiomyocyte necrosis remain largely unknown. Our recent genome-wide RNAi screen has identified a potential necrosis suppressor gene PRKAR1A , which encodes PKA regulatory subunit 1α (R1α). R1α is primarily known for regulating PKA activity based on cAMP level, by restraining PKA catalytic subunits in the absence of cAMP. Here, we showed that disruption of R1α augmented cardiomyocyte necrosis in vitro and in vivo , resulting in exaggerated myocardial I/R injury and contractile dysfunction. Mechanistically, R1α loss repressed the Nrf2 antioxidant transcription factor and aggravated oxidative stress following I/R. Degradation of the endogenous Nrf2 inhibitor Keap1 through p62-dependent selective autophagy was blocked by R1α depletion. Phosphorylation of p62 at Ser349 by mammalian target of rapamycin complex 1 (mTORC1), a critical step in p62-Keap1 interaction, was induced by I/R, but diminished by R1α loss. Activation of PKA by forskolin or isoproterenol almost completely abolished hydrogen peroxide-induced p62 phosphorylation. In conclusion, R1α loss induces unrestrained PKA activation and impairs the mTORC1-p62-Keap1-Nrf2 antioxidant defense system, leading to aggravated oxidative stress, necrosis and myocardial I/R injury. Our findings uncover a novel role of PKA in oxidative stress and necrosis. Therefore, PKA signaling may be exploited to develop new cardioprotective therapies.
Inflammatory molecular endotypes of nasal polyps derived from White and Japanese populations
Authors: Tsuguhisa Nakayama, Ivan T. Lee, Wei Le, Yasuhiro Tsunemi, Nicole A. Borchard, David Zarabanda, Sachi S. Dholakia, Philip A. Gall, Angela Yang, Dayoung Kim, Makoto Akutsu, Takashi Kashiwagi, Zara M. Patel, Peter H. Hwang, Daniel N. Frank, Shin-ichi Haruna, Vijay R. Ramakrishnan, Garry P. Nolan, Sizun Jiang, Jayakar V. Nayak
Journal: Journal of Allergy and Clinical Immunology (2021)
Abstract P339: Examining Cardiac Phenotypes Of EF Hand Containing Domain 1 Protein (EFHD1) Knockout Mice
Authors: David R Eberhardt, Xue Yin, Anthony Balynas, Sandra Lee, Maureen Walsh, Katsuhiko Funai, Dipayan Chaudhuri
Journal: Circulation Research (2021)

Mitochondrial dysfunction due to calcium overload is common in heart disease and results in heart failure. In a mouse model of mitochondrial cardiomyopathies we noted a substantial downregulation of the gene encoding for the EF hand containing domain 1 protein (EFHD1). EFHD1 is a mitochondrial protein which binds calcium and has been shown to stimulate both apoptosis and mitoflashes. These processes involve mitochondrial calcium overload. We therefore hypothesized that EFHD1 down regulation could represent a natural response by failing hearts to prevent mitochondrial calcium overload. We therefore studied the calcium handling properties of mice where Efhd1 had been knocked out (Efhd1-KO). These mice are viable and have no obvious adverse cardiac or metabolic phenotypes. We find that EFHD1 is expressed in the cytoplasm and mitochondrial outer membrane and intermembrane space. It associates strongly with endoplasmic reticulum (ER)-associated mitochondrial membranes. Moreover, mitochondria isolated from Efhd1-KO mice also exhibited 250±10 % improvement in calcium retention in liver but not heart, while neonatal mouse hearts were 3 times more resistant to hypoxia. These findings suggest that EFHD1 may modulate mitochondrial calcium uptake.
CTNI-04. RECURRENT GLIOBLASTOMA LONG-TERM SURVIVORS TREATED WITH CUSP9v3
Authors: Marc-Eric Halatsch, Richard Kast, Georg Karpel-Massler, Benjamin Mayer, Oliver Zolk, Bernd Schmitz, Angelika Scheuerle, Ludwig Maier, Lars Bullinger, Regine Mayer-Steinacker, Carl Schmidt, Katharina Zeiler, Ziad Elshaer, Patricia Panther, Birgit Schmelzle, Anke Hallmen, Annika Dwucet, Markus D Siegelin, Mike-Andrew Westhoff, Kristine Beckers, Gauthier Bouche, Tim Heiland
Journal: Neuro-Oncology (2021)

Abstract CUSP9v3 is a new treatment regimen for glioblastoma. It consists of continuous daily use of 9 drugs repurposed from general medicine. Their primary non-oncology uses are given in parentheses: aprepitant (nausea), auranofin (rheumatoid arthritis), celecoxib (pain), captopril (hypertension), disulfiram (alcohol abuse), itraconazole (fungal infection), minocycline (bacterial infection), ritonavir (viral infection) and sertraline (depression). All drugs have preclinical or clinical data indicating that they can retard glioblastoma growth, as reviewed in the published background papers. In CUSP9v3 all 9 medicines are given daily with added metronomic, low-dose (20 mg/m2 BSA twice daily) temozolomide. After 3 years of daily, uninterrupted use of CUSP9v3, of an initial cohort of 10 recurrent glioblastoma patients, as of May 2021, 3 are alive, functioning well, progression-free at 44, 44, and 57 months after recurrence and CUSP9v3 started. We report now that there were no unexpected toxicities from this combination of 10 daily drugs, although all patients required dose reduction of one or more of the drugs. CUSP9v3 was reasonably well-tolerated. Ritonavir, temozolomide, captopril and itraconazole were the drugs most frequently requiring dose reduction or pausing. The most common adverse events were nausea, headache, fatigue, diarrhea and ataxia. There were no treatment-related deaths. In the 3 long-term survivors, the median neutrophil-to-lymphocyte ratio decreased from 2.5 to 1.5 during CUSP9v3 treatment. In the group of the 3 shortest-term survivors that ratio increased from 4.7 to 14.3. CUSP9v3 follows the injunction of Palmer et al. that cancer therapy can be constructed using drug combinations that are independently effective, with non-overlapping mechanisms of action, and non-overlapping resistance pathways. We interpret the data accrued over the last few decades on the ever-shifting spatial and temporal growth drives active at any given moment in glioblastoma as requiring a complex pharmacological approach like CUSP9v3.
Abstract 11595: The Influence of Social Determinants on Heart Failure Outcomes: A Systematic Review
Authors: Alyssa Coleman, Kimberly R Enard, R. Aver Yakubu, Briona Butcher, Paul J Hauptman
Journal: Circulation (2021)

Introduction: Heart failure (HF) is an ongoing health concern that is expected to affect 9 million Americans by 2030. Growing research shows the association between non-clinical, social determinants of health (SDoH) and adverse outcomes (hospitalizations, high costs, and premature mortality). Providers must be able to identify SDoH risk factors to improve care delivery and patient outcomes. Aim: To summarize how SDoH risk factors have been included, defined, measured, and assessed in studies that examine outcomes in the HF care continuum. Methods: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines, a search of five databases was conducted for observational or interventional studies published between 2009 and 2021 that assessed the influence of SDoH risk factors on outcomes among subjects with HF. Study quality was assessed using NIH’s quality assessment tools. Results: The search identified 1,209 unique records; 108 were selected for full-text review. In total, 59 articles including retrospective and prospective cohort, cross-sectional, and intervention studies met criteria for inclusion. The majority of studies examined readmissions and hospitalizations (k=36); mortality or survival (k=32); and success of medical devices and transplantation (k=8). SDoH risk factors most commonly evaluated were race/ethnicity; age; gender; SES; social support; and education or health literacy. Studies used a range of 1-9 SDoH (M = 3.6, SD = 2.2) as primary independent variables and 0-7 SDoH as controls (M = 2.4, SD = 2.1). The studies used multiple data sources, frequently EMR linked with national surveys, disease registries, and/or data from large national studies. Overall, the effects of the SDoH risk factors on HF outcomes were mixed, and these differences appeared to be related to heterogeneity of data sources and SDoH constructs employed across studies. Conclusions: Our systematic review suggests that the influence of SDoH on HF outcomes remains incompletely assessed in part due to both inconsistent measurement and absence of potentially relevant variables. More expansive, real-time SDoH data collection is required if HF interventions are to meaningfully impact value-based and patient-centered models of care.
Decitabine Combined with Minimally Myelosuppressive Therapy for Induction of Remission of Pediatric High-Risk Acute Myeloid Leukemia with Chromosome 5q Deletion. a Report of Three Cases
Authors: Shengqin Cheng, Peifang Xiao, Juxiang Wang, Li Gao, Jiajia Zheng, Yixin Hu, Xin Ding, Jing Ling, Qin Lu, Jian Pan, Bohan Li, Jun Lu, Yi Wang, Raul C Ribeiro, Shaoyan Hu
Journal: Blood (2021)
Abstract 11267: Ibrutinib Treatment Results in Arrhythmia in Atrial-Specific Human Ipsc-Derived Cardiomyocytes
Authors: Matthew R Fleming, Lynn Hall, Laura Short, Christian Shaffer, Andrew Glazer, Javid J Moslehi, Dan M Roden
Journal: Circulation (2021)

Introduction: Cardiovascular sequelae of targeted cancer therapies may provide novel insights into cardiovascular biology and disease pathogenesis, including atrial fibrillation (AF). The Bruton tyrosine kinase (BTK) inhibitor ibrutinib has revolutionized treatment for B-cell malignancies but increases the incidence of AF compared with conventional chemotherapy. Recent data in mouse models have shown that ibrutinib mediated-AF likely results not from inhibition of BTK (“on target” effect), but from off-target inhibition of a different kinase, C-terminal Src kinase (CSK). The signaling pathway by which CSK inhibition results in AF remains unknown and thus may represent a novel mechanism for AF molecular pathogenesis. Methods: To study how CSK inhibition results in AF in a human derived model, we created atrial specific cardiomyocytes from human induced pluripotent stem cells (hiPSC-aCMs) from a healthy control. We studied cellular monolayers of hiPSC-aCMs using extracellular field potential (EFP) recordings obtained by the Nanion CardioExcyte 96 system after 24 hour exposure to vehicle, ibrutinib, or the second generation BTK inhibitor acalabrutinib. Results: Chamber specificity of hiPSC-aCMs was confirmed by Western blot analysis of subtype-specific markers. Treatment with ibrutinib for 24 hours resulted in striking increase in beat-to-beat variability in spontaneous contraction, an in vitro correlate of arrhythmogenic behavior (mean coefficient-of-variance/second following treatment 0.835 for ibrutinib vs. 0.198 for acalabrutinib vs. 0.165 for DMSO vehicle control, p&lt;0.001). Arrhythmogenic behavior was not seen with acalabrutinib, which does not appear to increase the incidence of AF in clinical trials. Conclusion: These experiments provide a novel method of screening for arrhythmogenic potential of targeted cancer therapies and validate atrial-specific hiPSC-CMs as a model system for the study of CSK mediated AF.
Risk of <i>N</i>-Nitrosodimethylamine (NMDA) Formation With Ranitidine—Reply
Authors: C. Michael White, Adrian V. Hernandez
Journal: JAMA (2021)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal