tbuckley/cabot-search huggingface dataset:
Abstract 14066: Control of Atrial Fibrillation With Short vs Long Duration of Continuous Intravenous Diltiazem
Authors: Nicole Sbircea, Emily Mathis, Brandon Pearce, Jennifer Mundell, Lindsay Saum
Journal: Circulation (2021)

Introduction: Continuous intravenous (IV) diltiazem is one of the options for urgent management of atrial fibrillation with rapid ventricular response (RVR). This study assesses the clinical outcomes of utilizing IV diltiazem for less than or greater than 24 hours. Methods: A retrospective chart-review of patients receiving continuous IV diltiazem between January 1, 2017 and December 31, 2018 where adult patients were included if they had atrial fibrillation with RVR and were treated with continuous IV diltiazem. Exclusion criteria included initiation of IV diltiazem in the ICU, strict nothing by mouth, only a bolus of IV diltiazem used, no conversion to oral rate controlling agent following discontinuation of IV diltiazem, and if pregnant. Infusions lasting &gt;24 hours and &lt;24 hours were compared. Primary objective was to evaluate duration in goal heart rate for the first 48 hours after conversion to PO diltiazem. Secondary outcomes included length of hospitalization, ICU transfer, 30-day readmission, and development of cardiovascular events including stroke, myocardial infarction, or cardiovascular death. Results: 146 out of 251 patients met inclusion criteria. 75.3% of patients maintained a goal heart rate (less than 110bpm) for at least 80% of the 48 hours after conversion to oral diltiazem in &lt; 24 hours group compared to only 59% (p =0.037). The &lt;24 hours group had more patients in heart rate goal for &gt;85% of 48 hours after conversion to oral diltiazem compared to the &gt;24 hours group (p=0.03). Diltiazem drips used for &gt;24 hours had a higher percentage of ICU transfers (p = 0.035) and longer hospitalization (p = 0.001). There were no differences regarding major adverse cardiovascular events and readmission rates. Conclusions: Diltiazem drip use for &lt;24 hours was associated with greater time spent in goal heart rate as well as a lower rate of ICU transfers and shorter hospitalization when compared to drips used &gt; 24 hours.
BTK Inhibitor Ibrutinib/Zanubrutinib Plus Bendamustine and Rituximab As the Initial Treatment for Chronic Lymphocytic Leukemia/ Small Lymphocytic Leukemia：a Single Arm Real-World Study
Authors: Huayuan Zhu, Wei Wu, Yeqin Sha, Ze Jin, Yilian Yang, Jingyan Qiu, Chongyang Ding, Zhen Wang, Chuanbing Shi, Chen Peng, Hongling Mi, Ruize Chen, Li Wang, Lei Fan, Wei Xu, Jianyong Li
Journal: Blood (2021)
Phase 1/2 Study of Nexi-001 Donor-Derived Multi-Antigen Specific CD8+ T Cells for the Treatment of Relapsed Acute Myeloid Leukemia (AML) after Allogeneic Hematopoietic Transplantation
Authors: Monzr M. Al Malki, Sumithira Vasu, Dipenkumar Modi, Miguel-Angel Perales, Lucy Y Ghoda, Donna Bui, Vineetha Edavana, Emily Lu, Sojung Kim, Lauren Suarez, Mathias Oelke, Daniel Bednarik, Robert D Knight, Juan C. Varela
Journal: Blood (2021)
Characteristics of a Comprehensive, Continuously Updated Longitudinal Database for Multiple Myeloma
Authors: C. Anthony Blau, Grace Nam, Leena Chhun, Cheng Zheng, Jayne Piboonvaranggoon, Jennifer Wren, Elora Mallick, Lauren Zelko, Michiko Wolcott, Carmen Lopez, Swathi Namburi, Sibel Blau, Francis M. Senecal, Robert McCroskey, Mehdi M. Moezi, Ayed O. Ayed, Ricardo Lopez Barquilla, Joshua Richter, William I. Bensinger, Paul G. Richardson, Kenneth C. Anderson
Journal: Blood (2021)
Physiological and pharmacological modulation of BAX
Authors: Adam Z Spitz, Evripidis Gavathiotis
Journal: Trends in Pharmacological Sciences (2021)

Bcl-2-associated X protein (BAX) is a critical executioner of mitochondrial regulated cell death through its lethal activity of permeabilizing the mitochondrial outer membrane (MOM). While the physiological function of BAX ensures tissue homeostasis, dysregulation of BAX leads to aberrant cell death. Despite BAX being a promising therapeutic target for human diseases, historically the development of drugs has focused on antiapoptotic BCL-2 proteins, due to challenges in elucidating the mechanism of BAX activation and identifying druggable surfaces of BAX. Here, we discuss recent studies that have provided structure-function insights and identified regulatory surfaces that control BAX activation. Moreover, we emphasize the development of small molecule orthosteric, allosteric, and oligomerization modulators that provide novel opportunities for biological investigation and progress towards drugging BAX.
Abstract 11709: The Impact of Hypertension on Disease Expression in Hypertrophic Cardiomyopathy
Authors: Thomas M Roston, iacopo olivotto, Sharlene Day, Victoria N Parikh, Michelle Michels, Jodie Ingles, Christopher Semsarian, Daniel L Jacoby, Steven D Colan, Joseph Rossano, Samuel Wittekind, James S Ware, Lin Zhang, Sara Saberi, Adam S Helms, Carolyn Ho
Journal: Circulation (2021)

Introduction: Pressure overload from hypertension (HTN) is an important cause of left ventricular hypertrophy (LVH) in the general population, however its impact on disease expression in hypertrophic cardiomyopathy (HCM), and differences based on the presence/absence of a sarcomeric gene variant are not well characterized. Hypothesis: HTN is associated with more prominent manifestations of HCM. Methods: Genotyped HCM patients in the Sarcomeric Human Cardiomyopathy Registry were designated SARC+ ((likely) pathogenic sarcomeric variant present) or SARC- and categorized as having HTN (≥140/90 mmHg) or normal blood pressure (nonHTN; &lt;140/90 mmHg). Heart failure (HF; LVEF&lt;35%, NYHA III-IV, transplant/LVAD), ventricular arrhythmias (VA; sudden death, resuscitated arrest, appropriate ICD discharge), atrial fibrillation (AF), and an overall composite (HF, VA, AF, death) were assessed by Kaplan-Meier analysis and logistic regression. Results: Of 1706 patients (62% male), 445 (26%) had HTN. Median follow up was 4.2 years. SARC+ nonHTN patients were youngest and SARC- HTN patients oldest (p&lt;0.001; Table). Obstructive physiology was most common in SARC- HTN. SARC+ nonHTN patients had the greatest wall thickness, although absolute differences were minimal (Table). HTN was associated with HF and the overall composite outcome, but not VA or AF (Figure). On multivariable analysis, HTN predicted the HF composite (OR 1.59 [95% CI 1.07-2.26], p=0.02), especially in SARC+ patients (OR 2.34 [95% 1.33-4.11], p=0.003). Conclusions: HTN is associated with worse HF outcomes in HCM, especially among SARC+ patients, but has minimal impact on the degree of cardiac remodeling.
Debulking before Initiation of Venetoclax Therapy in Untreated Patients with Chronic Lymphocytic Leukemia: Results from a Phase 3b Study
Authors: Ian W. Flinn, David Andorsky, Jason Melear, Sudhir Manda, Bertrand Anz, Kathryn Kolibaba, Habte Yimer, John M. Burke, Suzanne Fanning, Jay Courtright, Miguel Islas-Ohlmayer, Suman Kambhampati, Tamas Vizkelety, John Pesko, Brenda Chyla, Dingfeng Jiang, Jeff P. Sharman
Journal: Blood (2021)
Abstract 12685: Feasibility and Safety of Vascular Closure Devices After Undergoing Leadless Pacemaker Implantation
Authors: ivan mendoza, Jorge Penalver, Ninoska N Aranguibel, Jose Chamorro, Juan zambrano, Cesar Mendoza, joao Braghiroli, Isabella A Ramalho, Daisy A Castiblanco, Ivan Mendoza
Journal: Circulation (2021)

Introduction: Transcatheter pacing systems have recently emerged as a safe and effective alternative in treating patients who require right ventricular pacing therapy. Traditionally, the right femoral venous was the preferred insertion site for the 23 French Micra introducer catheter due to the manufactured design of the delivery system. Vascular closure of the venous access has been performed with figure 8 closure technique and manual pressure . There is no data supporting the use of closure devices in this specific procedure. The purpose of this study was to assess the feasibility and safety of vascular closure devices after undergoing implantation of the leadless pacemaker device. Methods: One hundred and eighty ( 180 ) consecutive patients who had undergone implantation of a Micra transcatheter pacing were evaluated. One hundred and sixty eight ( 168 ) patients had traditional vascular closure after implantation and twelve ( 12 ) received the Perclose vascular closure device for the femoral venous access . A t-test analysis was used to compare patient demographics total procedure times and complications rates Results: None of the 180 patients suffered complications during the procedure. The mean procedure time using the traditional figure eight technique was 21.24 min versus 30.67 min (P = 0.01) by the closure device . The mean number of recaptures required for the patients undergoing the traditional venous closure was 0.48 vs. 0.67 (P = 0.70) by the closure device Conclusions: The Perclose device appears safe and feasible alternative for the vascular closure after implantation of the Micra transcatheter leadless pacemaker system. This approach tends to have longer procedure times
Abstract 9592: Acute Kidney Injury Subphenotypes in Critically Ill Patients with Cardiovascular Diseases by Latent Class Analysis: A Retrospective Cohort Study
Authors: Qi Guo, Yong Xie, Yongqing Huang, Shuxian Zhou, Yangxin Chen, Jingfeng Wang
Journal: Circulation (2021)

Introduction: According to the potential heterogeneity of acute kidney injury (AKI) in critically ill patients with cardiovascular diseases, we explored the subphenotypes of AKI and evaluated the prognostic differences among AKI subphenotypes. Hypothesis: We hypothesized that patients with different AKI subphenotypes would suffer different prognosis. Methods: Clinical information from the Medical Information Mart for Intensive Care (MIMIC)-III database was enrolled. Latent class analysis (LCA) was used to explore the potential subphenotypes of AKI in critically ill patients with cardiovascular diseases. The number of classes was identified using the Bayesian information criterion and entropy. The differences in prognostic ability among the AKI subphenotypes were evaluated by logistic regression analysis. Results: In this study, a total of 7738 AKI patients were enrolled and divided into 4 heterogeneous subphenotypes by using LCA. The subphenotypes showed remarkable dofference from kidney disease classified by improving Global Outcomes (KDIGO) stages. Notedly, though both dominated by stage 2, the mortality between class 4 and class 1 classified by LCA were significantly different (15.2% vs. 1.6%, p &lt;0.05). The trend remained the same after further adjustment, with an odds ratio of 12.31 (95% confidence interval, 8.96-16.89). Conclusions: LCA was feasible for AKI classification and different subphenotypes prognosis prediction in critically ill patients with cardiovascular disease. Our study revealed the potential heterogeneity of AKI patients, which is worthy of further investigation.
Abstract 10320: Feasibility of the Telehealth Assessment and Skill-Building Kit for Stroke Family Caregivers
Authors: Tamilyn Bakas, Heidi Sucharew, Bonnie J Brehm, Kari Dunning, Michael J McCarthy, Matthew Rota, Jahmeel Israel, Kelly E Stacy, Brett M Kissela, Elaine L Miller
Journal: Circulation (2021)

Introduction: Existing stroke family caregiver interventions are limited in the use of technology and lack focus on caregiver health. The Telehealth Assessment and Skill-Building Kit (TASK III) was optimized based on caregiver preferences for technology and goal setting to improve caregiver health. The purpose of this study was to test feasibility of the TASK III program compared with an Information, Support, and Referral group (ISR) for improving caregiver depressive symptoms, life changes, and unhealthy days. Methods: Using randomized control trial design and an intent-to-treat analysis, 74 stroke family caregivers were randomized to TASK III (n=36) or ISR (n=38). The TASK III Resource Guide was provided by hard copy, website, eBook, and USB drive. TASK III and ISR groups received an American Stroke Association (ASA) pamphlet, access to the ASA website, and 8 weekly calls from a nurse (telephone/videoconferencing), with a booster call a month later. Data trends from baseline to 8 and 12 weeks were explored for depressive symptoms (PHQ-9), life changes (Bakas Caregiving Outcomes Scale), and unhealthy days. Minutes on calls with the nurse were controlled in analyses. Results: Among caregivers with mild to severe depressive symptoms at baseline (PHQ-9 &gt; 5) (n=31), TASK III showed a greater reduction in depressive symptoms relative to ISR from baseline to 8 and 12 weeks (Mean group difference in change scores -3.7, p=.02 at 8 weeks; -3.7, p=.04 at 12 weeks). Using the full sample (N=74), life changes improved for TASK III relative to ISR from baseline to 8 and 12 weeks (Mean 8.1, p=.03; 14.9, p&lt;.01), and for specific life changes of emotional well-being (Mean 0.8, p=.05; 1.4, p=.01) and physical health (0.7, p=.07; 1.2, p&lt;.01). No significant differences in rate ratios were found for unhealthy physical (Rate ratio 1.7, p=.17; 1.1, p=.74) and mental days (Rate ratio 1.4 p=.22; 1.4, p=.25). Conclusions: Data trends supported feasibility of TASK III relative to ISR for improving depressive symptoms and life changes, including changes in emotional well-being and physical health. Unhealthy days were highly skewed and not sensitive to change. Testing efficacy of TASK III relative to ISR is warranted in a future, well-powered trial.
Spatially Resolved Transcriptomic Analysis of Acute Kidney Injury in a Female Murine Model
Authors: Eryn E. Dixon, Haojia Wu, Yoshiharu Muto, Parker C. Wilson, Benjamin D. Humphreys
Journal: Journal of the American Society of Nephrology (2021)

Significance Statement AKI is characterized by a sudden loss of kidney function often followed by the restoration of function through repair. Single-cell RNA sequencing efforts have aided in the identification of cell types and states important in injury, repair, and failed repair. These transcriptomic atlases lack spatial information, complicating interpretation of relevant cellular interactions. Therefore, we generated a spatial time course of female ischemic injury, defining temporal and location-specific gene expression patterns of injury markers. Gene expression and cell type interactions were resolved across time points using computational tools Giotto and SPOTlight. These results have been packaged into an interactive data visualization tool for gene target discovery and validation throughout the kidney and AKI research communities. Background Single-cell sequencing technologies have advanced our understanding of kidney biology and disease, but the loss of spatial information in these datasets hinders our interpretation of intercellular communication networks and regional gene expression patterns. New spatial transcriptomic sequencing platforms make it possible to measure the topography of gene expression at genome depth. Methods We optimized and validated a female bilateral ischemia-reperfusion injury model. Using the 10× Genomics Visium Spatial Gene Expression solution, we generated spatial maps of gene expression across the injury and repair time course, and applied two open-source computational tools, Giotto and SPOTlight, to increase resolution and measure cell-cell interaction dynamics. Results An ischemia time of 34 minutes in a female murine model resulted in comparable injury to 22 minutes for males. We report a total of 16,856 unique genes mapped across our injury and repair time course. Giotto, a computational toolbox for spatial data analysis, enabled increased resolution mapping of genes and cell types. Using a seeded nonnegative matrix regression (SPOTlight) to deconvolute the dynamic landscape of cell-cell interactions, we found that injured proximal tubule cells were characterized by increasing macrophage and lymphocyte interactions even 6 weeks after injury, potentially reflecting the AKI to CKD transition. Conclusions In this transcriptomic atlas, we defined region-specific and injury-induced loss of differentiation markers and their re-expression during repair, as well as region-specific injury and repair transcriptional responses. Lastly, we created an interactive data visualization application for the scientific community to explore these results (http://humphreyslab.com/SingleCell/).
Abstract 14813: The Cardiac Microvasculature in Heart Failure With Preserved Ejection Fraction: An Autopsy Study
Authors: Saad Hussain, Selma F Mohammed, Joseph J Maleszewski, Edwards D William, Sultan A Mirzoyev, Margaret M Redfield
Journal: Circulation (2013)

Background: Patients with heart failure (HF) and preserved ejection fraction (HFpEF) have impaired left ventricular (LV) systolic and diastolic reserve function in the absence of epicardial coronar...
Overactive bladder in women
Authors: Daniel Beder, Pamela Ashton, Vibhash Mishra
Journal: BMJ (2021)

### What you need to know

A 65 year old woman presents to her general practitioner complaining of knee pain. She reports that this makes it difficult for her to get to the toilet in time. On further questioning, she describes urinary frequency and urgency with occasional incontinence episodes, and explains that she knows where all the toilets are on her regular commutes. 

The collection of urinary symptoms described above typically constitute the overactive bladder syndrome (OAB), which has a prevalence of more than 20%, and affects women more commonly than men.12 Prevalence increases with age, and it is common for patients to seek help late because of embarrassment or the belief that it is a normal part of ageing.34 In our experience, discussion of urinary symptoms in primary care is often brought up tangentially or as a “door handle conversation.” Over and above its own morbidity, delayed diagnosis of OAB can be a contributing factor to many other mental and physical health issues such as depression, stress, and falls and fractures.56 This article offers an approach to an initial consultation with a patient experiencing OAB symptoms. We refer to women, but this article may also apply to some transgender and non-binary people.

The International Continence Society defines OAB as “urinary urgency, usually accompanied by urinary frequency and nocturia, with or without urgency urinary incontinence, in the absence of urinary tract infection or other obvious pathology.”7 The diagnostic process therefore aims to characterise the lower urinary tract symptoms experienced …
Abstract 11768: Role of Endothelial Shear Stress and Endothelial Shear Stress Gradient in Plaques Associated With Acute Erosion vs. Stable Control Plaques and Relationship Between Plaque Slope and Localization of Plaque Erosion
Authors: Diaa Hakim, Ahmet U Coskun, Charles Maynard, zhongyue pu, Deborah Rupert, Nicholas Cefalo, Tej Sheth, Natalia Pinilla-Echeverri, Kajander A Olli, Gerasimos Siasos, Michail I Papafaklis, Stefanu Kostas, Lampros K Michalis, Kevin Croce, Peter H Stone
Journal: Circulation (2021)

Introduction: The role of endothelial shear stress (ESS) in the development of coronary plaque erosion is unknown. High ESS gradient (ESSG) has been hypothesized to promote plaque erosion, but no studies have included matched control stable plaques with the same minimal and reference lumen area (MLA, RLA, respectively). No studies examined the location of plaque erosion (proximal vs distal to MLA of the culprit plaque) related to the max magnitude of upslope vs downslope of the lumen obstruction. Aims: (1) to compare ESSG between plaques with erosion and similar control plaques that remained stable; (2) among erosion plaques, to study the effect of max slope steepness (Δ lumen area/frame) up- and down-stream from the culprit plaque MLA on thrombus location. Methods: We studied 46 patients from TOTAL and COMPLETE trials who underwent angiography and OCT imaging: 46 arteries: 27 LAD, 6 LCX, 13 RCA. Plaques were divided into Plaque Erosion (n=24) with OCT features of erosion before PCI (17 definite, 7 probable erosion) and matched coronary plaques from separate control patients (n=22) without plaque disruption. Orthogonal angiographic views were used to generate a 3-D arterial reconstruction, and angio centerline was combined with OCT centerline. Local ESS distribution was assessed by computational fluid dynamics and reported in consecutive 3-mm segments. Among the plaque erosions, we calculated the up- and down-slope (Δ lumen area/frame) of lumen obstruction for each culprit plaque. Results: See Table Conclusion: In plaques with similarly severe obstruction, plaque erosion is associated with higher max ESS and max ESSG vs plaques that remain stable. Proximal plaque erosion/thrombus is associated with steeper plaque upslope vs downslope, and distal plaque erosion/thrombus is associated with steeper plaque downslope vs upslope. Absolute ESSG is higher in downslope vs upslope erosions. These features may help prognosticate individual plaques at risk for future erosion.
The CBFβ-SMMHC/NRP1 Axis Regulates FLT3 and TGF-Beta Pathways in Inv(16) Acute Myeloid Leukemia
Authors: Mahesh Hegde, Mohd Hafiz Ahmad, Rui Li, Anneliese Carrascoso, Roger Mulet-Lazaro, Ruud Delwel, John H. Bushweller, Monica L. Guzman, Scot A. Wolfe, Julie Zhu, Lucio H. Castilla
Journal: Blood (2021)
NIMG-29. ELEVATION OF GLUTAMINE AND CITRATE BY MR SPECTROSCOPY IS AN IMAGING BIOMARKER OF RAPID CELL PROLIFERATION IN GLIOMAS
Authors: Vivek Tiwari, Pegah Askari, Elizabeth Maher, Changho Choi
Journal: Neuro-Oncology (2021)

Abstract Prior studies suggested glutamine metabolism in cancers may be altered to meet the high demands of nucleotide biosynthesis in cancers. We conducted 1H MR spectroscopy in 18 glioma patients and analyzed the metabolic data together with post-gadolinium MRI and cell proliferation rate (MIB-1 label index). The optimized MRS (TE 97 ms PRESS) provided well discernible signal of glutamine at 2.45 ppm and a negative-polarity signal of citrate at 2.6 ppm, without considerable overlaps with neighboring signals. The 18 patients had biopsy-proven anaplastic gliomas or glioblastomas. Concurrent elevation of glutamine and citrate was identified in 15 gliomas. These gliomas presented with enhancement in post-gadolinium MRI, indicative of broken blood-brain barrier (BBB). The 15 gliomas were grouped as subset-1 while the other 3 gliomas that had elevated citrate without elevation of glutamine were grouped as subset-2. Citrate level was significantly different between the two subsets of gliomas (1.4+/-0.5 vs. 1.6+/-0.4 mM). However, subst-1 had significantly higher choline (4.7+/-1.8 vs. 1.6+/-0.3 mM, p&amp;lt; 0.01) and higher MIB-1 compared with subset-2. Given that choline is a cellularity marker, a finding of high choline and high MIB-1 with elevation of glutamine and citrate suggests that the tumors have high tumor cellularity and cell multiplication competence. Of the 18 gliomas, 13 were IDH mutated with elevated 2HG. The glutamine and citrate levels in IDH-mutant gliomas were not significantly different from those in IDH wildtype gliomas. In conclusion, high-grade gliomas undergo a metabolic rearrangement of concurrent elevation of glutamine and citrate to attain malignant characters such as high cellularity, rapid cell proliferation, and BBB breakdown. IDH mutant and IDH wildtype gliomas may share a common metabolic rearrangement of glutamine-mediated citrate elevation to attain malignancy. Measurements of glutamine and citrate may serve a potential imaging biomarker for aggressive gliomas.