tbuckley/cabot-search huggingface dataset:
Isolated CNS Hemophagocytic Lymphohistiocytosis in Children:What We Know, What We Don't Know ?
Authors: Selin Aytac, Gunay Balta, Baris Kuskonmaz, Tekin Aksu, Fatma Visal Okur, Sule Unal, Duygu Uckan, Fatma Gumruk
Journal: Blood (2021)
Abstract 10806: The Association of Hemoglobin Drop with In-Hospital Outcomes in Covid-19 Patients
Authors: Toshiki Kuno, Yoshihisa Miyamoto, Masao Iwagami, Miho Ishimaru, Mai Takahashi, Natalia Egorova
Journal: Circulation (2021)

Background: Bleeding events can be critical in hospitalized patients with COVID-19, especially those with aggressive anticoagulation therapy. Objective: We aimed to investigate whether hemoglobin drop associated with increased risk of acute kidney injury (AKI) and in-hospital mortality among patients with COVID-19. Methods: This retrospective study was conducted by review of the medical records of 6,683 patients with laboratory confirmed COVID-19 hospitalized in the Mount Sinai Health system between March 1 st , 2020 and March 30 th 2021. We compared patients with and without hemoglobin drop &gt;3g/dL during hospitalization within a week after admissions, using inverse probability treatment weighted analysis (IPTW). Outcomes of interest were in-hospital mortality and AKI which was defined as increased of creatine 1.5 times or 0.3mg/dL. Results: Of the 6,683 patients admitted due to COVID-19, 750 (11.2%) presented with a marked hemoglobin drop. Patients with hemoglobin drop were more likely to receive therapeutic anticoagulation within two days after admissions. Patients with hemoglobin drop had higher crude in-hospital mortality (40.8% versus 20.0%, P&lt;0.001) as well as AKI (51.4% versus 23.9%, P&lt;0.001) compared to those without. IPTW analysis showed that hemoglobin drop was associated with higher in-hospital mortality compared to those without (odds ratio (OR) [95% confidential interval (CI)]: 2.21 [1.54-2.88], P&lt;0.001) as well as AKI (OR [95% CI]: 2.79 [2.08-3.73], P&lt;0.001). Finally, the smooth spline curve showed the association of hemoglobin drop and adjusted odds ratio for in-hospital mortality, which reflected the association of hemoglobin drop and in-hospital mortality (Figure). Conclusions: Hemoglobin drop during COVID-19 related hospitalizations was associated with a higher risk of AKI and in-hospital mortality. Figure Legends: Smooth spline curve of the association of hemoglobin drop and adjusted odds ratio of in-hospital mortality.
Standardization in the Diagnosis of Mixed Phenotype Acute Leukemia (MPAL): Semiquantitative, Universally Applicable Flow Cytometric Criteria for Immunophenotypic Lineage Assignment and Isolated MPO
Authors: Alexandra E. Kovach, Sunil S. Raikar, Matthew J. Oberley, Gerald Wertheim, Karen R Rabin, Jyotinder N. Punia, Alix E. Seif, Reuven J Schore, Dragos C. Luca, Terri Guinipero, William G Woods, Viviane Cahen, Maurice R.G. O'Gorman, Etan Orgel, Brent L. Wood
Journal: Blood (2021)
Abstract 11298: Tablet-Based Echocardiography is a Valuable Tool to Effectively Evaluate Patients with Sars-Cov-2 While Limiting Sonographer Exposure
Authors: David M Leone, Stephen Ghiroli, Ruchika Karnik, Erin Faherty, Dina Ferdman
Journal: Circulation (2021)

Background: The SARS-Cov-2 virus and the associated Multi-System Inflammatory Syndrome in Children (MIS-C) can cause myocardial injury, cardiac dysfunction, and coronary dilation. This makes echocardiography a key component during clinical evaluation. To improve technician safety, we implemented a protocol utilizing a tablet-based echocardiography (TBE) system to evaluate patients who had active COVID-19 or whose testing was pending. We hypothesized that appropriate clinical evaluations could be completed with TBE while having a shorter exposure time for personnel. Methods: We retrospectively evaluated 35 patients at a tertiary, pediatric hospital between March 2020 and May 2021 who underwent TBE. We compared the TBE findings and duration to comprehensive echocardiograms done on average two weeks later with a traditional machine. A complete study included evaluation of ventricular function, coronary artery diameter, and pericardial fluid assessment. Pro-brain natriuretic peptide (pro-BNP) and troponin-T levels were reviewed. Subjects were divided into two groups based on an elevation in troponin-T as a surrogate for myocardial injury (Trop + and Trop - ). Results: Eight subjects had cardiac dysfunction with 6/12 being from the Trop + group and 2/23 in the Trop - group. The mean troponin-T elevation was 0.32 ng/mL. Pro-BNP levels were elevated in all but 1 of the 35 subjects but were ten times higher in the trop + group (mean 18,055 vs 1,888 pg/mL; p = 0.001). Three subjects with MIS-C had coronary dilation noted by TBE (2 in Trop + and 1 in Trop - ) with one persistently dilated at follow up. TBE findings such as coronary dilation or cardiac dysfunction guided medical therapies and no clinically relevant findings were missed when compared to studies at follow up. TBE was on average 29 minutes shorter (41 ± 18 vs 12 ± 5 min; p &lt; 0.001). One patent ductus arteriosus was found by TBE and this was confirmed on repeat imaging. Conclusions: TBE allows for experienced sonographers to limit exposure time to potentially contagious patients and easier decontamination while not compromising essential clinical information. This study shows TBE is a useful tool to effectively evaluate patients during highly contagious viral respiratory outbreaks.
Abstract 10869: Using All-Cause Mortality to Determine the Best Method for Indexation of Echocardiographic Measures According to Body Size in Obese and Non-Obese Patients
Authors: Angus Fung, Dhnanjay Soundappan, Daniel Loewenstein, David Playford, Geoff Strange, Rebecca Kozor, James Otton, Martin Ugander
Journal: Circulation (2021)

Introduction: Body surface area (BSA) is the most widely accepted metric for body size indexation of cardiac measures to improve diagnosis, but its use in obesity is questioned. Furthermore, big data analyses comparing indexation metrics are limited. Hypothesis: All-cause mortality can be used to identify an optimal indexation metric for transthoracic echocardiographic (TTE) measures that will be a better predictor of survival than BSA regardless of obesity (body mass index [BMI] ≥30kg/m2). Methods: Patients (n=11621) with no prior cardiac surgery, with all TTE measures of interest available, were selected from the National Echo Database Australia. Cox regression survival analysis for all-cause mortality (Wald chi-square) was analyzed for TTE measures both unindexed and indexed to different indexation metrics. Results: For both non-obese (n=7684, median BMI 25 kg/m2, age 65 years, 42% female, 4.2 years follow-up, 1586 deaths) and obese patients (n=3937, BMI 34 kg/m2, age 63 years, 42% female, 4.5 years follow-up, 607 deaths), indexation of cardiac sizes (atrial areas, left ventricular mass and diameter, and aortic sinus diameter) to BSA had better prognostic performance (higher chi-square) vs unindexed measures. Indexing by height^2.7 performed worse than BSA. Cardiac output had the best prognostic performance when indexed by weight^3 vs all other metrics (&gt;3-fold higher chi-square). Stroke volume performed better unindexed than when indexed for body size. Conclusions: When using all-cause mortality as the arbiter of appropriateness among both non-obese and obese patients, indexation by BSA improved prognostic performance, cardiac output performed best when indexed by weight^3, and stroke volume performed best unindexed.
Abstract 14163: Mathematical Model for Predicting Survival in Elderly (Above 80 Years) Population After Primary Percutaneous Coronary Intervention for ST Elevation Myocardial Infarction
Authors: Aaruni Saxena, Shahnaz Jamil Copley, Nikesh Jathanna, Nikola Sprigg, Akhlaque Uddin
Journal: Circulation (2021)

Introduction: Advancement in interventional cardiology has increased the number of percutaneous coronary intervention (PCI) in the elderly. However, clinicians still face tough decision making to select elderly patients who can receive Primary PCI and have improved survival. This study aimed to identify factors that influence the survival in elderly population undergoing PPCI for treatment of ST elevation myocardial infraction (STEMI). Methods: We analyzed the data at our cardiac center prospectively during 2010- 2019 and developed a mathematical model using multi-parameter regression analysis using SPSS and OriginPro data visualization. Results: The factors which may predict survival were identified with help of mathematical model developed on the basis of clinical parameters reported at the time of STEMI presentation and details of the PCI procedure in 248 patients (male = 124, Age 85.78±3.43 years, , female= 124, Age 85.78± 4.08 years, ). The data visualization is shown in figure 1 and the developed model equation is as follows: Y (survival in months) = 126.865 - 0.258 (± 0.030) (Hb in g/dl) - 0.105(± 0.034) (Creatinine in umol/L) - 0.228 (± 0.112) (eGFR in ml/min/1.73 m 2 ) - 4.174 (±2.443) (triglycerides in mmol/l) - 1.201 (± 1.232) (LDL in mmol/l) - 0.001(±0.002) (Call to balloon time in minutes) + 16.874 (±3.119) (log 10 radiation dose)- 1.224(±0.352) Age at time of presentation) (N = 248, R = 0.636, F= 18.043, p = 0.00) Conclusions: Our study shows that hemoglobin, kidney function, lipid profile, call to balloon time, age of the patient at time of STEMI presentation and radiation dose used during the procedure may be important predictors for the survival of patient after PPCI. Nevertheless the patient age at the time of STEMI is negatively correlated with survival period. Similarly, early intervention in event of STEMI will decrease call to balloon time thereby increasing post-procedure survival in elderly patients .
NIMG-04. PREDICTING THE BRAF MUTATIONAL STATUS IN PATIENTS WITH MELANOMA BRAIN METASTASES USING RADIOMICS - A BICENTRIC STUDY
Authors: Anna-Katharina Meissner, Robin Gutsche, Norbert Galldiks, Martin Kocher, Stephanie T Juenger, Marie-Lisa Eich, Christina Wendl, Roland Goldbrunner, Maximilian Ruge, Cornelia Mauch, Martin Proescholdt, Stefan Grau, Philipp Lohmann
Journal: Neuro-Oncology (2021)

Abstract BACKGROUND The BRAF V600E mutation is present in approximately 50% of patients with melanoma and is an important prerequisite for a response to targeted therapies such as BRAF inhibitors. In the majority of patients, the BRAF mutational status is based on the analysis of tissue samples from the extracranial primary tumor only. Since the extracranial and intracranial BRAF mutational status may be discrepant, the additional information on the BRAF mutational status of melanoma brain metastases would be of clinical value, e.g., for the prediction of response to targeted therapies. Here, we evaluated the potential of MRI radiomics for the determination of the intracranial BRAF mutational status in patients with melanoma brain metastases. PATIENTS AND METHODS Fifty-nine patients with melanoma brain metastases from two university hospitals (group 1, 45 patients; group 2, 14 patients) were operated with subsequent genetic analysis of the intracranial BRAF mutational status. All patients underwent structural MRI preoperatively. Areas of contrast enhancement were manually segmented and analyzed. Group 1 was used for model training and validation, group 2 for model testing. After image preprocessing and radiomics feature extraction, a test-retest analysis was performed to identify robust features prior to feature selection. Finally, the best performing radiomics model was applied to the test data. Diagnostic performances were evaluated using receiver operating characteristic (ROC) analyses. RESULTS Twenty-two patients (49%) in group 1, and 6 patients (43%) in group 2 had an intrametastatic BRAF V600E mutation. Using the best performing six parameter radiomics signature, a linear support vector machine classifier yielded an area under the ROC curve (AUC) of 0.92 (sensitivity, 83%; specificity, 88%) in the test data. CONCLUSION The developed radiomics classifier allows a non-invasive prediction of the intracranial BRAF V600E mutational status in patients with melanoma brain metastases and may be of value for treatment decisions.
Abstract 9797: Efficacy and Safety of Bempedoic Acid in Patients with Metabolic Syndrome
Authors: Michael D Shapiro, Pam R Taub, Michael J Louie, Lei Lei, Christie M Ballantyne
Journal: Circulation (2021)

Metabolic syndrome (MetS) is associated with increased risk of cardiovascular events. Bempedoic acid (BA) is an ATP citrate lyase inhibitor that lowers LDL-C in patients with hypercholesterolemia. We investigated the lipid-lowering efficacy, safety, and effect of BA on glycemic parameters and high-sensitivity C-reactive protein (hsCRP) according to baseline metabolic status using pooled data (n=3623) from 4 phase 3, randomized, double-blind studies in which patients were randomized 2:1 to BA or placebo (PBO) for 12-52 weeks. Patients with diabetes mellitus (n=1114) were excluded from the analyses. The remaining patients were categorized as having MetS (n=936; defined using modified IAS guidelines with BMI as a proxy for waist circumference) or nonMetS (n=1573). Assessments included absolute or % change from baseline to week 12 in LDL-C, other lipid parameters, hemoglobin A 1c (HbA 1c ), fasting plasma glucose (FPG), and hsCRP; and treatment-emergent adverse events (TEAEs). Background statin intensity was similar between groups (Table). BA significantly lowered LDL-C at week 12 vs PBO, to a greater extent in patients with MetS than nonMetS (PBO-corrected % change from baseline of –22.3 MetS; –18.4 nonMetS; interaction P =.0472). BA also significantly lowered total cholesterol, non-HDL-C, and apo B % change at week 12 vs PBO to a similar extent in both subgroups. In patients with MetS, absolute reductions in HbA 1c and FPG were significantly greater with BA vs PBO; changes in HbA 1C and FPG were not significantly different for BA vs PBO in the nonMetS group (interaction P =.0003 and .0017, respectively). hsCRP % change from baseline was substantially lowered with BA vs PBO in both groups (insignificant interaction based on log of hsCRP absolute change). The incidence of TEAEs was comparable in both subgroups. Overall, BA demonstrated comparable safety in both metabolic subgroups and greater lowering of LDL-C, HbA 1c , and FPG levels in patients with MetS vs nonMetS.
Abstract 14372: The Acquired Long QT-Causing Drugs Haloperidol and Terfenadine Cause Defects in HERG Trafficking
Authors: Abagail McKernan, Haider Mehdi, Alexander Greiner, Jin-Young Yoon, Diana Colgan, Jason Dierdorff, Barry London
Journal: Circulation (2021)

Background: Mutations in K v 11.1 (HERG) cause inherited long QT syndrome (LQTS) type 2 by disrupting channel function or membrane trafficking. Acquired LQTS is caused by drug binding to HERG and directly blocking the channel pore, reducing I Kr and prolonging QTc in persons with decreased repolarization reserve. Alternatively, these drugs could bind to HERG and interfere with trafficking, reducing the number of HERG channels at the membrane. Objective: We sought to understand the effects of known acquired LQTS-causing drugs from various classes (terfenadine, haloperidol, ondansetron, fluconazole, azithromycin) on HERG trafficking. Methods: HEK293 cells stably expressing HERG (HERG-HEK293) were cultured in varying concentrations of selected drugs for 24 hours. Differences in trafficking were identified by immunoblot using the terminally-glycosylated HERG at 155 kD and the immature core-glycosylated HERG at 135 kD. Both the mutant HERG-G601S and HERG-HEK293 cells treated for 24 hours with arsenic trioxide (As 2 O 3 ) served as trafficking-deficient controls. Results: HERG-HEK293 cells treated with haloperidol ( &gt; 50 μM) demonstrated a decrease in the size of the terminally glycosylated band, appearing at 140-145 kD in comparison to the fully glycosylated 155 kD (Fig. 1A). HERG-HEK293 cells treated with terfenadine ( &gt; 15 μM) demonstrated a deficiency in terminal glycosylation (Fig. 1B). Ondansetron, fluconazole, and azithromycin treatments at 1, 10, and 100 μM demonstrated no effect on the fully glycosylated band. Conclusions: These data suggest terfenadine and haloperidol interfere with HERG trafficking, resulting in less mature HERG at the membrane. Together, these data provide insight into a non-pore blocking mechanism that may underlie some cases of acquired LQTS.
Recent breakthroughs and future directions in drugging aquaporins
Authors: Mootaz M. Salman, Philip Kitchen, Andrea J. Yool, Roslyn M. Bill
Journal: Trends in Pharmacological Sciences (2021)

Aquaporins facilitate the passive transport of water, solutes, or ions across biological membranes. They are implicated in diverse pathologies including brain edema following stroke or trauma, epilepsy, cancer cell migration and tumor angiogenesis, metabolic disorders, and inflammation. Despite this, there is no aquaporin-targeted drug in the clinic and aquaporins have been perceived to be intrinsically non-druggable targets. Here we challenge this idea, as viable routes to inhibition of aquaporin function have recently been identified, including targeting their regulation or their roles as channels for unexpected substrates. Identifying new drug development frameworks for conditions associated with disrupted water and solute homeostasis will meet the urgent, unmet clinical need of millions of patients for whom no pharmacological interventions are available.
Abstract 11022: Aspirin with Ticagrelor or with Low-Dose Rivaroxaban for Secondary Prevention; A Cost per Outcome Analysis
Authors: Gal Tsaban, Hilmi Alnsasra, Ala Abu-Dogosh, Itai Weissberg, Yael Ben-Baruch Golan, Orit Barrett, Roi Westreich, Enis Aboalhasan, Ariel Hammerman, Joseph Azuri, Ronen Arbel
Journal: Circulation (2021)

Introduction: Secondary prevention of cardiovascular events among patients with diagnosed cardiovascular disease and high ischemic risk poses a significant challenge in clinical practice. Both Ticagrelor and low-dose (LD) Rivaroxaban have shown superiority in preventing major adverse cardiovascular events (MACE) than aspirin treatment alone. The comparative value for money of these two regimens remains unexplored. Hypothesis: Ticagrelor and LD-Rivaroxaban are comparable in their clinical efficacy and cost-effectiveness. Methods: We analyzed the annualized cost needed to treat (CNT) of each regimen by multiplying the annualized number needed to treat (aNNT) by the annual cost of each drug. The aNNTs were based on outcome data from PEGASUS TIMI-54 and COMPASS trials. Scenario analyses were performed to overcome variances in terms of population risk. Costs were based on 2021 US prices. Secondary outcomes analysis was performed for myocardial infarction (MI), stroke, and CV death as separate outcomes. Results: The aNNTs to prevent MACE with Ticagrelor and with LD-Rivaroxaban were 207 [95% confidence interval (CI):138-553] and 147 (95%CI:104-252), respectively. At an annual cost of $3,541 versus $4,308, the corresponding CNTs were 734,429$ (95%CI:489,619$-1,958,478$) with ticagrelor and 633,003$ (95%CI:446,826$-1,085,149$) with LD-Rivaroxaban. Results of the scenario and secondary outcomes analysis are presented in Figure 1 . Conclusions: LD-Rivaroxaban provides better value for money than Ticagrelor for secondary prevention of MACE. Ticagrelor offers an advantage over LD-Rivaroxaban specifically to prevent MI and should be considered in cases where MI is the primary concern.
Clinical Characteristics and Outcomes of Patients with Newly Diagnosed De Novo Acute Myeloid Leukemia (AML) during the COVID-19 Pandemic
Authors: Hari S. Raman, Yael Flamand, Marlise R. Luskin, Daniel J. DeAngelo, Richard M. Stone, Jacqueline S. Garcia, Martha Wadleigh, Anne Charles, Kevin Copson, R. Coleman Lindsley, Rahul S. Vedula, Eric S. Winer
Journal: Blood (2021)
Abstract 12926: The Impact of Thoracic Aortic Aneurysm versus Dissection on Postoperative Outcomes After Thoracic Endovascular Aortic Repair
Authors: James Brown, Derek Serna-Gallegos, Edgar Aranda-Michel, Sarah Yousef, Yisi Wang, Forozan Navid, Courtenay Dunn-Lewis, Ibrahim A Sultan
Journal: Circulation (2021)

Introduction: As thoracic endovascular aortic repair (TEVAR) is the standard of care for complicated Type B aortic dissection (TBAD) and descending thoracic aortic (DTA) aneurysm, it is critical to understand its outcomes and utilization. Hypothesis: Nationwide postoperative complications, admission costs, and 30- and 90-day readmissions after TEVAR are between TBAD and aneurysm. Methods: Codes from the International Classification of Diseases (ICD) 9 and 10 identified patients with a primary procedure code for TEVAR from 2010-2017 in the Nationwide Readmissions Database (with trend weights to generate national estimates). After ICD codes identified patients with thoracic or thoracoabdominal aortic dissection as well as aortic aneurysm, the two groups were compared. Mixed model logistic regression identified variables associated with readmission, treating individual hospital as a random effect. Results: An estimated 6594 patients underwent non-elective TEVAR, of which 4649 (70.5%) had TBAD and 1945 (29.5%) had aneurysm of the DTA. Patients with aneurysms were more likely to be older, be women, have cardiovascular disease, and have chronic pulmonary disease than patients with TBAD. In-hospital mortality was lower for aneurysm (5.7% vs. 10.9%, p&lt;0.001) than TBAD. For patients with aneurysm, there was less stroke (4.6% vs. 7.1%), paraplegia (2.2% vs. 3.9%), acute kidney injury (18.2% vs. 34.5%), and mesenteric ischemia (2.0% vs. 5.8%) than TBAD. Patients with aneurysm had lower total cost of care during their index admission (48.0 vs. 65.2 x $1000) than TBAD. The proportion of 30-day and 90-day readmissions were similar across each group, with overall 30-day readmission being 23.6%, while 90-day readmission was 38.2%. On multivariable adjustment, aneurysm was not associated with increased odds of 30-day readmission (OR 1.02, 95% CI: 0.84, 1.25, p=0.820) or 90-day readmission (OR 0.97, 95% CI: 0.80, 1.19, p=0.780) compared to TBAD. Conclusions: While TBAD was associated with worse in-hospital mortality and higher incidence of complications, aortic disease was not associated with an increased odds of readmission through 90 days. However, the incidence of early readmission was substantial for patients undergoing non-elective TEVAR.