tbuckley/cabot-search huggingface dataset:
Abstract 11909: Racial and Gender Differences in Lifetime Healthcare Costs Across Cardiovascular Risk Factors
Authors: Rohan Khera, Mengni Liu, Nitin Kondamudi, Erica S Spatz, Colby Ayers, Tiffany Powell-wiley, Ethan A Halm, Ambarish Pandey
Journal: Circulation (2021)

Background: Healthcare costs pose a major challenge, but their assessment is limited to major healthcare events. An understanding of the burden of healthcare costs over the lifetime of individuals, particularly among those with cardiovascular risk factors (CRFs) and among disadvantaged groups based on race and sex, has important implications for health of individuals. Methods: We linked the longitudinal multiethnic Dallas Heart Study that recruited participants in 2000-2002 with inpatient and outpatient claims from all hospitals in the Dallas-Fort Worth metroplex through 2018, capturing encounter costs. Hypertension, diabetes, hyperlipidemia, smoking, and overweight/obesity as CRFs were defined at cohort enrollment. For each individual, costs were indexed to age and cumulated over follow up with missing costs imputed using chained random forests with predictive mean matching. Lifetime costs across race, sex, and CRFs were evaluated as interactions in generalized additive models with costs modeled as a 4 th order function of age landmarked at 40y. Results: 2091 individuals (mean age, 45 [10] y; 62% women, 53% Blacks) were included. Among those with inpatient or outpatient care, median lifetime cumulative healthcare costs at age 40y were $84809 (IQR, $187958, $2777270). Lifetime healthcare costs were significantly higher in Blacks vs non-Blacks ($97401 vs $73918; P &lt; .01), particularly in advanced age (P, age-race interaction &lt;.001). There were modestly higher costs among men. Lifetime costs were progressively higher with more CRFs. After accounting for CRFs, Blacks and men with CRFs had higher lifetime costs than matched non-Blacks and women, respectively (P interaction &lt;.001) ( Figure ). Discussion: Black individuals and men are burdened by higher lifetime healthcare costs, with disproportionately higher costs among Blacks with the same CRFs. Costs differences also emerge in old age, highlighting the need for early prevention of risk factors among Blacks.
Abstract 13120: Short-Term Outcomes of Transcatheter Aortic Valve Replacement in Very Low Gradient Severe Aortic Stenosis
Authors: Giorgio A Medranda, Richard Schwartz, Stephen Green
Journal: Circulation (2021)

Introduction: Hemodynamic improvements following transcatheter aortic valve replacement (TAVR) have been show to correlate with outcomes. TAVR in patients with severe aortic stenosis (AS) and low mean gradients (MG) (&lt;40mmHg) have demonstrated significant improvements in their MG post-TAVR. However, data on low, intermediate and high-risk patients with severe AS and very low MGs (&lt;20mmHg) are lacking. Hypothesis: We hypothesized that patients with very low gradient severe AS see smaller improvements in MG but similar outcomes following TAVR using contemporary transcatheter heart valves (THV). Methods: This was a retrospective, observational study of 1114 low-, intermediate- or high-risk patients who underwent TAVR at our institution between 2015-2020. We trichotomized our population based on their pre-TAVR MG (cohort 1 (n=71): &lt;20mmHg, cohort 2 (n=506): 20-39mmHg, cohort 3 (n=537): &gt;40mmHg). We examined pre-TAVR and post-TAVR echocardiographic data. We examined in-hospital, 30-day and 1-year outcomes. Statistical analysis of outcomes was performed using two-sided t-test and one-way ANOVA. Results: Among the 1114 who underwent TAVR, 776 utilized the SAPIEN 3 or SAPIEN 3 Ultra THV and 338 utilized the CoreValve Evolut PRO THV. The patients had a mean age of 80.9 years with a mean Society of Thoracic Surgeons score of 6.4%. Patients in cohort 1 (15.4mmHg to 8.4mmHg, p&lt;0.0001), cohort 2 (30.3mmHg to 9.6mmHg, p&lt;0.0001) and cohort 3 (53.4mmHg to 11.6mmHg, p&lt;0.0001) all saw significant improvement in their MG post-TAVR. Patients saw similar rates of death and stroke out to 1 year (Table 1). Conclusions: Our study of 1114 low-, intermediate- and high-risk patients who underwent contemporary TAVR demonstrated significant improvements in post-TAVR MGs across all variants of severe AS which translated to excellent short-term outcomes.
Paralog knockout profiling identifies DUSP4 and DUSP6 as a digenic dependence in MAPK pathway-driven cancers
Authors: Takahiro Ito, Michael J. Young, Ruitong Li, Sidharth Jain, Andreas Wernitznig, John M. Krill-Burger, Christopher T. Lemke, Davide Monducci, Diego J. Rodriguez, Liang Chang, Sanjukta Dutta, Debjani Pal, Brenton R. Paolella, Michael V. Rothberg, David E. Root, Cory M. Johannessen, Laxmi Parida, Gad Getz, Francisca Vazquez, John G. Doench, Mahdi Zamanighomi, William R. Sellers
Journal: Nature Genetics (2021)
Over half of general practices in England would quit primary care networks, indicative ballot shows
Authors: Gareth Iacobucci
Journal: BMJ (2021)

More than half of the general practices in England would be willing to withdraw from primary care networks in response to the government’s “rescue package” for the profession, results from the BMA’s indicative ballot earlier this month have suggested.

The BMA undertook the ballot to ask GPs whether they would consider undertaking four types of industrial action after its General Practitioners Committee formally rejected the government and NHS England’s contentious plan to improve access to general practice.12

Between 1 and 14 November the BMA surveyed the 5144 practices in England that have a …
Abstract 14104: Levosimendan Effects on In-Hospital Outcomes in Patients With Cardiogenic Shock
Authors: ANGELA VENUTI, Stefania Sacchi, elena cinel, Bianca Gattari, Luca Baldetti, Francesco Calvo, Vittorio Pazzanese, Mario Gramegna, Alberto Maria Cappelletti
Journal: Circulation (2021)

Introduction: Cardiogenic Shock (CS) is a life-threatening condition characterized by low cardiac output, end-organ hypoperfusion and hypoxia. Inotropic pharmacological support is recommended to restore proper hemodynamic in these patients. Levosimendan is a calcium-sensitizer with unique features, since it exerts inotropic effects preventing myocardial oxygen consumption. In CS patients, its effects on in-hospital outcomes are not well known. Hypothesis: The aim of the study was to assess whether in CS patients, levosimendan administration on top of standard inotropic support could affect in-hospital outcomes. Methods: We retrospectively reviewed clinical data of 41 CS patients admitted to Cardiac Intensive Care Unit (CICU). We compared clinical course and outcomes, including length of stay (LOS), length of mechanical support (LMS) and in-hospital mortality, between CS patients receiving levosimendan on top of standard inotropic support (group 1) and not-receiving ones (group 2). Results: Overall, 41 patients [83% males, mean age 65.8 ± 13.01 years, mean left ventricular ejection fraction (LVEF) 26.75 ± 13.28%] with CS due to acute coronary syndrome (ACS) in 19 (46.34 %), acute decompensated heart failure (ADHF) in 21 (51.22 %) and myocarditis in 1 (2.44%) were included. Eleven (26.83%) patients received levosimendan on top of standard inotropic support (group 1) while 30 (73.17%) were not-receiving (group 2). Between the two groups, any difference was observed in baseline LVEF (p= 0.14), ACS and ADHF aetiologies (p=0.98, p=0.14). Mechanical support rate was similar between patients receiving and not receiving levosimedan (p=0.05), while LMS was higher in group 1 (p= 0.001). Both CICU and in-hospital LOS were longer in group 1 (p=0.0001, p= 0.004). Conversely, CICU and in-hospital mortality did not differ between the two groups (p=0.9, p=0.72). Conclusion: In CS patients, levosimendan administration on top of standard inotropic support did not improve in-hospital outcomes.
Abstract 14170: Incremental Value of Magnetic Resonance-Based Ventricular and Atrial Strain in Predicting Ventricular Arrhythmia
Authors: Kei Nakata, Julia Cirillo, Amanda Paskavitz, Jennifer Rodriguez, Trishna Sadhwani, Tuyen Yankama, Jonathan W Waks, Warren J Manning, Long H Ngo, Daniel B Kramer, Reza Nezafat
Journal: Circulation (2021)

Introduction: Only a small subset of patients with primary prevention ICDs, for whom left ventricular ejection fraction (LVEF) is emphasized in current guidelines, receive appropriate ICD therapy. Objectives: To study the incremental value of cardiovascular MR (CMR)-derived right and left ventricular and left atrial strain measured using feature tracking in predicting ventricular arrhythmia in patients eligible for implantable cardioverter-defibrillator (ICD) primary prevention of ventricular arrhythmia. Methods: The study included patients who met the current clinical guideline to receive an ICD for primary prevention of SCD. CMR imaging was performed on either a 1.5 or a 3T scanner, including standard evaluation of LV function and structure, LV/RV/LA strains, LGE. Outcomes were comprised of 1) unstable VT/VF &gt;30sesonds, 2) appropriate ICD therapy; shock or anti-tachycardia pacing for VT/VF, or 3) SCD. The primary outcome was a composite endpoint of any of the above three outcomes. Results: A total of 239 patients were included and the average age was 57±14 years old. Patients with outcomes had slightly lower RV global longitudinal strain (GLS). Univariate Cox proportional hazards regression showed that every standard deviation increase in RV GLS was associated with a 73% increase in risk (p&lt; 0.01). The baseline multivariable Cox’s proportional hazards regression model with a standardized clinical risk score, standardized LVEF, LGE had an AUC of 0.64. The best performing model, which included standardized LV and RV GLS, significantly improved prognosis compared with the baseline model, with an AUC of 0.72 and a categorical free NRI of 0.88 (p=0.04). Model 1 indicated an increased risk of 77% for every standard deviation increase in RV GLS (p&lt; 0.01) and a decreased risk of 49% for every standard deviation increase in LV GLS (p= 0.02). Kaplan-Meier curves could be stratified using the selected thresholds; LV GCS ≥ 5.3 and RV GLS ≥ -10.8, respectively (p=0.02, p&lt;0.01).
M-Protein Sequencing and Monitoring in Serum of LC-Only Multiple Myeloma Patients
Authors: Mariya Liyasova, Natalia Migdal, Zac McDonald, Liqiang Yang, Bin Ma, Jesus Giovanni Piza, Donna E. Reece, Elisabet E. Manasanch, Robert Z. Orlowski, Suzanne Trudel, Gregory P. Kaufman
Journal: Blood (2021)
Analysis of COVID-19 Infection and Mortality Among Patients With Psychiatric Disorders, 2020
Authors: Antonio L. Teixeira, Trudy Millard Krause, Lopita Ghosh, Lokesh Shahani, Rodrigo Machado-Vieira, Scott D. Lane, Eric Boerwinkle, Jair C. Soares
Journal: JAMA Network Open (2021)

People with major psychiatric disorders are more likely to have comorbidities associated with worse outcomes of COVID-19. This fact alone could determine greater vulnerability of people with major psychiatric disorders to COVID-19.To assess the odds of testing positive for and mortality from COVID-19 among and between patients with schizophrenia, mood disorders, anxiety disorders and a reference group in a large national database.This cross-sectional study used an electronic health record data set aggregated from many national sources in the United States and licensed from Optum with current and historical data on patients tested for COVID-19 in 2020. Three psychiatric cohorts (patients with schizophrenia, mood disorders, or anxiety disorders) were compared with a reference group with no major psychiatric conditions. Statistical analysis was performed from March to April 2021.The exposures observed include lab-confirmed positivity for COVID-19 and mortality.The odds of testing positive for COVID-19 in 2020 and the odds of death from COVID-19 were measured.The population studied included 2 535 098 unique persons, 3350 with schizophrenia, 26 610 with mood disorders, and 18 550 with anxiety disorders. The mean (SD) age was 44 (23) years; 233 519 were non-Hispanic African American, 1 583 440 were non-Hispanic Caucasian; and 1 580 703 (62%) were female. The schizophrenia cohort (positivity rate: 9.86%; adjusted OR, 0.90 [95% CI, 0.84-0.97]) and the mood disorder cohort (positivity rate: 9.86%; adjusted OR, 0.93 [95% CI, 0.87-0.99]) had a significantly lower rate of positivity than the anxiety disorder cohort (positivity rate: 11.17%; adjusted OR, 1.05 [95% CI, 0.98-1.12) which was closer to the reference group (11.91%). After fully adjusting for demographic factors and comorbid conditions, patients with schizophrenia were nearly 4 times more likely to die from the disease than the reference group (OR, 3.74; 95% CI, 2.66-5.24). The mood disorders COVID-19 cohort had a 2.76 times greater odds of mortality than the reference group (OR, 2.76; 95% CI, 2.00-3.81), and the anxiety disorders cohort had a 2.39 times greater odds of mortality than the reference group (OR, 2.39; 95% CI, 1.68-3.27).By examining a large database while controlling for multiple confounding factors such as age, race and ethnicity, and comorbid medical conditions, the present study found that patients with schizophrenia had much increased odds of mortality by COVID-19.
Diffuse Large B-Cell Lymphoma: Optimizing Therapy for Relapsed/Refractory Disease
Authors: Matthew J. Matasar
Journal: Journal of the National Comprehensive Cancer Network (2021)

Despite a growing therapeutic arsenal to treat relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL), outcomes remain poor. Only approximately half of patients with this disease are eligible to receive curative autologous stem cell transplant, and of those, only half will be cured. Moreover, for patients who are transplant-ineligible, there are few effective options. Dr. Matthew J. Matasar discussed the current unmet needs in the treatment of patients with R/R DLBCL, treatment strategies in the second- and third-line settings, and emerging therapeutic options.
Abstract 13279: Real-Time Arrhythmia Detection in Intensive Care Unit Using a Hybrid Convolutional Neural Network Approach
Authors: Sandeep Chandra Bollepalli, Rahul K Sevakula, Wan-Tai M Au-Yeung, Mohamad Kassab, Faisal M Merchant, George Bazoukis, Richard Boyer, Eric M Isselbacher, Antonis Armoundas
Journal: Circulation (2021)

Background: Intensive care units (ICUs) admit high-risk patients whose physiological parameters are continuously monitored to provide timely care. However, traditional ICU monitors are known to generate high rate of false alarms (FAs) resulting in alarm fatigue. In this work, we investigate the use of a hybrid convolutional neural network (CNN) architecture aiming to reduce the burden of FAs. Methods and Results: We retrospectively analyzed 953 independent life threatening alarms from the streaming data of 410 ICU patients. Specifically, we used four channels of electrocardiographic (ECG), arterial blood pressure (BP) and photoplethysmographic (PPG) signals to detect noise in each of the physiological signals, as well as the onset of an arrhythmia. To this end, we developed a hybrid CNN architecture that fuses the information from multiple physiological signals as well as the handcrafted features (Figure 1). Using 5-fold cross validation repeated for 5 times, we obtained an arrhythmia detection accuracy of 87.5% with a standard deviation of 0.5% (Table 1). In practice, the proposed hybrid-CNN algorithm would have suppressed 77.05% of the FA generated by an existing monitoring system, without prior knowledge of the underlying alarm, which is superior to any other published algorithm. Evaluation on the PhysioNet 2015 Challenge database achieved an overall classification accuracy of 93.9%, indicating its efficacy and generalizability. Further, our method remains adaptable to various arrhythmic conditions as well as multiple physiological signals. Conclusions: A hybrid CNN architecture can significantly reduce FA burden and hence improve the quality of care in ICUs
Cannabis Use and Patient-Centered Care During Pregnancy and Post Partum Among People Living With HIV
Authors: Kelly C. Young-Wolff, Julia L. Marcus, Derek D. Satre
Journal: JAMA Network Open (2021)

Lynn M. Yee, MD, MPH; Deborah Kacanek, ScD; Chase Brightwell, MS; Lisa B. Haddad, MD, MPH; Jennifer Jao, MD, MPH; Kathleen M. Powis, MD, MPH, MBA; Tzy-Jyun Yao, PhD; Emily Barr, MSN, CPNP, CNM; Carly Broadwell, MS; Suzanne Siminski, MS, MBA; George R. Seage III, DSc, MPH; Ellen G. Chadwick, MD; Pediatric HIV/AIDS Cohort Study
Abstract 12269: Investigating Arrhythmogenic Potential of a Novel KCNH2 Mutation Leading to Long QT Syndrome
Authors: Bright Tsevi, Akwasi D Akwaboah, Jacqueline A Treat, Robert Goodrow, Victoria Lam, Anthony Owusu-Mensah, Michel Audette, Jonathan M Cordeiro, Makarand Deo
Journal: Circulation (2021)

Background: Mutations in the gene KCNH2 have been associated with both Short and Long QT syndrome. In this study, we identified a 1-day old infant that exhibited T-wave alternans coupled with Long QT Syndrome leading to aborted sudden infant death. Methods: Genetic analysis of the patient revealed a mutation in KCNH2 resulting in a proline to leucine substitution at position 632 (P632L). Functional electrophysiological studies were performed with the hERG mutation transiently transfected into either Human Embryonic Kidney (HEK) cells or human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). The functional effects of P632L were incorporated into biophysical computational models of hiPSC-CM as well as adult human cardiomyocytes to further assess its arrhythmogenic potential. Results: The male infant displayed multiple repolarization disorders including T-wave alternans and a QTc =510 ms that appeared 1 day after birth. Genetic screening revealed a heterozygous missense mutation (P632L) in KCNH2 in the infant. Patch clamp analysis of HEK cells transiently transfected with P632L mutation showed a complete loss of function of HERG current compared to WT HERG. Transient transfection of P632L into WT hiPSC myocytes resulted in prolongation of the hiPSC action potential compared to untransfected hiPSC myocytes. Co-transfection of WT and non-functional P632L channels into HEK cells resulted in a dramatic loss of current suggesting a dominant negative effect. Implementing the effects of a complete block of HERG current in the hiPSC-CM computer model prolonged the action potential by 45% and depolarized the resting membrane potentials. In adult human myocyte models, the effects of HERG blockade were more severe in Purkinje cells than that in ventricular myocytes (71% vs. 16% APD prolongation, respectively). Conclusions: The mutation P632L causes a complete loss of HERG current and results in QT prolongation. Numerical simulations suggest a more severe phenotype in Purkinje cells than in ventricular myocytes which could be proarrhythmic.
Uniaxial and Coaxial Vertical Embedded Extrusion Bioprinting
Authors: Liming Lian, Cuiping Zhou, Guosheng Tang, Maobin Xie, Zixuan Wang, Zeyu Luo, Julia Japo, Di Wang, Jianhua Zhou, Mian Wang, Wanlu Li, Sushila Maharjan, Marina Ruelas, Jie Guo, Xunwei Wu, Yu Shrike Zhang
Journal: Advanced Healthcare Materials (2021)

The 3D bioprinting technologies have attracted increasing attention due to their flexibility in producing architecturally relevant tissue constructs. Here, a vertical embedded extrusion bioprinting strategy using uniaxial or coaxial nozzles is presented, which allows formation of vertical structures of homogeneous or heterogeneous properties. By adjusting the bioprinting parameters, the characteristics of the bioprinted vertical patterns can be precisely controlled. Using this strategy, two proof-of-concept applications in tissue biofabrication are demonstrated. Specifically, intestinal villi and hair follicles, two liner-shaped tissues in the human body, are successfully generated with the vertical embedded bioprinting method, reconstructing some of their key structures as well as restoring partial functions in vitro. Caco-2 cells in the bioprinted intestinal villus constructs proliferated and aggregated properly, also showing functional biomarker expressions such as ZO-1 and villin. Moreover, preliminary hair follicle structures featuring keratinized human keratinocytes and spheroid-shaped human dermal papilla cells are formed after vertical bioprinting and culturing. In summary, this vertical embedded extrusion bioprinting technique harnessing a uniaxial or coaxial format will likely bring further improvements in the reconstruction of certain human tissues and organs, especially those with a linear structure, potentially leading to wide utilities in tissue engineering, tissue model engineering, and drug discovery.
RADT-25. PROTON THERAPY FOR YOUNG ADULT MEDULLOBLASTOMA: ACUTE TOXICITY AND DISEASE CONTROL OUTCOMES
Authors: I-Chia Liu, Adam Holtzman, Ronny Rotondo, Daniel Indelicato, Sridharan Gururangan, Robert Cavaliere, Christopher Morris, Daryoush Tavaniepour, Michael Rutenberg
Journal: Neuro-Oncology (2021)

Abstract BACKGROUND Report disease control, survival outcomes, and acute radiotherapy related toxicity among young adult medulloblastoma patients who received proton craniospinal irradiation (CSI) as part of multimodality therapy. We reports the completion rates of planned adjuvant chemotherapy. METHODS All adult medulloblastoma patients (≥ 22 years old) who received postoperative proton CSI +/- chemotherapy at our institution between 2008 and 2020 were included. Patient, disease, and treatment details along with prospectively obtained patient-reported acute CSI toxicities were collected (CTCAE v3 or v4). Acute hematologic data were analyzed. RESULTS Twenty young adult medulloblastoma patients were included. The median age at diagnosis was 27 years (range, 22–30). 45% had high-risk disease. 75% received chemotherapy, most of whom (65%) received post-CSI chemotherapy. Eight patients (40%) received concurrent vincristine with CSI. The median CSI dose was 36 GyE (range, 23.4-36) with a median tumor bed boost of 54 GyE (54-55.8). The median duration of radiotherapy was 44 days (range, 40-49). There were no acute ≥ grade 3 gastrointestinal or hematologic toxicities attributable to CSI (during or within 4 weeks after completion of RT). Grade 2 nausea and vomiting affected 25% and 5% of patients, respectively. Acute grade 2 hematologic toxicity affected 36% of patients. Among patients planned to receive adjuvant chemotherapy (n=13), 100% completed at least 4 cycles and 85% completed all planned chemo cycles. With a median follow-up of 3.1 years, 4-year actuarial local control, DFS, and OS were 90% (95% CI 53-99), 90% (95% CI 53-99), and 95% (95% CI 72-99), respectively. Two patients had disease recurrence, both with local failures in the high dose boost volume in the tumor bed. CONCLUSIONS Proton radiotherapy for CSI in young adult medulloblastoma patients is well tolerated and shows promising disease control and survival outcomes. These data support the standard use of proton CSI for adult medulloblastoma.