tbuckley/cabot-search huggingface dataset:
Abstract 15947: Predictors and Characteristics of Malignant Arrhythmias in Patients on Ambulatory Inotropic Therapy
Authors: Christopher S Grubb, Lauren Truby, Maryjane Farr, Angelo B Biviano, Hasan Garan, Hirad Yarmohammadi
Journal: Circulation (2020)

Introduction: Ambulatory inotropic therapy (AIT) is used in advanced heart failure as a bridge to advanced therapies or palliation. Inotropes are known arrhythmogenic agents. The characteristics, predictors and outcomes of ventricular tachycardia (VT) and ventricular fibrillation (VF) in this population are not well studied. Methods: This is a retrospective analysis of patients discharged on AIT. Patients were followed from AIT initiation until transplant, ventricular assist device placement, death, or wean from inotropes. Those without an ICD were excluded. All data was obtained through chart review. Results: We included 160 patients (mean age 60±13 years; 70% male). Milrinone was the selected inotrope in 94%. VT/VF occurred in 37/160 (23%) a median 2.6 months after AIT initiation. 20/37 (54%) had a VT/VF event within 3 months. 25/160 (16%) received ICD shocks and 40/160 (25%) received anti-tachycardia pacing (ATP). Inappropriate shocks for atrial arrhythmias occurred in 5 (3.1%). Of 59 episodes with available interrogation data, 70% were VT and 30% were VF. ATP successfully resolved 18/59 (14%), shocks were used in 33/59 (56%), and 8/59 (14%) resolved without device therapy. The mean VT cycle length was 284±63 ms with an average VT/VF time of 44±99 seconds. In univariate analysis previous VT/VF was predictive of VT/VF on AIT (HR: 2.54; 95% CI 1.33-5.86; p=0.01). Beta blocker therapy was protective (HR: 0.45; 95% CI 0.21-0.99; p=.05). Those patients with a VT/VF event in the first 3 months of AIT have higher 1 year mortality (80.4% vs 87.7%, p=0.02, Fig. 1). Prior to AIT initiation, VT/VF had occurred in 52 (33%) patients. Of the 108 patients with no history of VT/VF prior to AIT initiation, 19 (18%) had a de novo episode of VT/VF. Conclusions: Patients on AIT are at risk of ventricular arrhythmias. Those with previous VT/VF are at increased risk, but 15-20% with no previous events will have VT/VF. VT/VF within 3 months of AIT initiation may worsen prognosis and increase mortality.
Primary myelofibrosis: 2021 update on diagnosis, risk‐stratification and management
Authors: Ayalew Tefferi
Journal: American Journal of Hematology (2020)

Primary myelofibrosis (PMF) is a myeloproliferative neoplasm (MPN) characterized by stem cell-derived clonal myeloproliferation that is often but not always accompanied by JAK2, CALR, or MPL mutations. Additional disease features include bone marrow reticulin/collagen fibrosis, aberrant inflammatory cytokine expression, anemia, hepatosplenomegaly, extramedullary hematopoiesis (EMH), constitutional symptoms, cachexia, leukemic progression, and shortened survival.Bone marrow morphology is the primary basis for diagnosis. Presence of JAK2, CALR, or MPL mutation, expected in around 90% of the patients, is supportive but not essential for diagnosis; these mutations are also prevalent in the closely related MPNs, namely polycythemia vera (PV) and essential thrombocythemia (ET). The 2016 World Health Organization classification system distinguishes "prefibrotic" from "overtly fibrotic" PMF; the former might mimic ET in its presentation. Furthermore, approximately 15% of patients with ET or PV might progress into a PMF-like phenotype (post-ET/PV MF) during their clinical course.SRSF2, ASXL1, and U2AF1-Q157 mutations predict inferior survival in PMF, independent of each other and other risk factors. RAS/CBL mutations predicted resistance to ruxolitinib therapy.Very high risk abnormalities include -7, inv (3), i(17q), +21, +19, 12p-, and 11q-.Two new prognostic systems for PMF have recently been introduced: GIPSS (genetically-inspired prognostic scoring system) and MIPSS70+ version 2.0 (MIPSSv2; mutation- and karyotype-enhanced international prognostic scoring system). GIPSS is based exclusively on mutations and karyotype. MIPSSv2 includes, in addition, clinical risk factors. GIPSS features four and MIPSSv2 five risk categories.Observation alone is advised for MIPSSv2 "low" and "very low" risk disease (estimated 10-year survival 56%-92%); allogeneic hematopoietic stem cell transplant (AHSCT) is the preferred treatment for "very high" and "high" risk disease (estimated 10-year survival 0%-13%); treatment-requiring patients with intermediate-risk disease (estimated 10-year survival 30%) are best served by participating in clinical trials. In non-transplant candidates, conventional treatment for anemia includes androgens, prednisone, thalidomide, and danazol; for symptomatic splenomegaly, hydroxyurea and ruxolitinib; and for constitutional symptoms, ruxolitinib. Fedratinib, another JAK2 inhibitor, has now been FDA-approved for use in ruxolitinib failures. Splenectomy is considered for drug-refractory splenomegaly and involved field radiotherapy for non-hepatosplenic EMH and extremity bone pain.A number of new agents, alone or in combination with ruxolitinib, are currently under investigation for MF treatment (ClinicalTrials.gov); preliminary results from some of these clinical trials were presented at the 2020 ASH annual meeting and highlighted in the current document.
Deubiquitinase USP7 contributes to the pathogenicity of spinal and bulbar muscular atrophy
Authors: Anna Pluciennik, Yuhong Liu, Elana Molotsky, Gregory B. Marsh, Bedri Ranxhi, Frederick J. Arnold, Sophie St.-Cyr, Beverly Davidson, Naemeh Pourshafie, Andrew P. Lieberman, Wei Gu, Sokol V. Todi, Diane E. Merry
Journal: Journal of Clinical Investigation (2020)

Polyglutamine (polyQ) diseases are devastating, slowly progressing neurodegenerative conditions caused by expansion of polyQ-encoding CAG repeats within the coding regions of distinct, unrelated genes. In spinal and bulbar muscular atrophy (SBMA), polyQ expansion within the androgen receptor (AR) causes progressive neuromuscular toxicity, the molecular basis of which is unclear. Using quantitative proteomics, we identified changes in the AR interactome caused by polyQ expansion. We found that the deubiquitinase USP7 preferentially interacts with polyQ-expanded AR and that lowering USP7 levels reduced mutant AR aggregation and cytotoxicity in cell models of SBMA. Moreover, USP7 knockdown suppressed disease phenotypes in SBMA and spinocerebellar ataxia type 3 (SCA3) fly models, and monoallelic knockout of Usp7 ameliorated several motor deficiencies in transgenic SBMA mice. USP7 overexpression resulted in reduced AR ubiquitination, indicating the direct action of USP7 on AR. Using quantitative proteomics, we identified the ubiquitinated lysine residues on mutant AR that are regulated by USP7. Finally, we found that USP7 also differentially interacts with mutant Huntingtin (HTT) protein in striatum and frontal cortex of a knockin mouse model of Huntington's disease. Taken together, our findings reveal a critical role for USP7 in the pathophysiology of SBMA and suggest a similar role in SCA3 and Huntington's disease.
A Bioinspired, Sustained‐Release Material in Response to Internal Signals for Biphasic Chemical Sensing in Wound Therapy
Authors: Wing‐Fu Lai, Ryan Deng, Tingchao He, Wing‐Tak Wong
Journal: Advanced Healthcare Materials (2020)

Abstract Biofluorescence in living entities is a functional process associated with information conveyance; whereas the capacity to respond to internal physiological signals is a unique property of a cell. By integrating these two biological features into materials design, a bioinspired material, namely CPS, is developed. Contrary to conventional luminescent polymeric systems whose emission comes from π ‐conjugated structures, this material displays clusterization‐triggered emission. In the preclinical trial on a dermal punch model of tissue repair, it successfully increases the rate of wound closure, reduces inflammatory cell infiltration, and enhances collagen deposition. It can also relay changes in internal chemical signals into changes in its intrinsic luminescence for biphasic chemical sensing to prevent possible occurrence of skin hyperpigmentation caused by minocycline hydrochloride in wound therapy. Together with its ease of fabrication, high biocompatibility, high drug loading efficiency, and high release sustainability, CPS shows high potential to be developed into an intelligent solid‐state device for wound treatment in the future.
Abstract 15094: In Patients on Warfarin, Does a History of Depression Impact Time in Therapeutic Range and Subsequent Dementia Risk?
Authors: Stacey Knight, Heidi T May, Scott Woller, Scott Stevens, Raymond O McCubrey, Tami L Bair, Jeffrey L Anderson, Joseph B Muhlestein, T Jared J Bunch
Journal: Circulation (2020)

Objective: Both time in therapeutic range (TTR) for anticoagulation and depression are associated with dementia risk. However, it is unknown if depression impacts TTR or their combined effect on dementia risk. Methods: We studied 14,953 patients who were chronically anticoagulated with warfarin (target INR 2-3) for atrial fibrillation (AF), venous thromboembolism (VTE), or a mechanical heart valve and managed by the Intermountain Healthcare Clinical Pharmacist Anticoagulation Service from 2003 to 2015. We excluded patients with a diagnosis of dementia before or within the first six months of warfarin management. TTR was evaluated as a continuous variable and by categories: ≤25%, 26-50%, 51-75%, and &gt;75%. We examined the association of depression to TTR using finite mixture modeling and utilized multivariable Cox hazard regression to determine the association of TTR and depression to 3-year dementia incidence. Results: Forty percent (n=6055) of patients were diagnosed with depression while on warfarin therapy. Patients with depression were younger, female, taking warfarin for VTE, and had more comorbidities. They also had a lower TTR compared to patients without depression; after adjustment for baseline differences, depressed patients had an average TTR decrease of 4% (p&lt;0.0001), and were 1.3 times more likely to have TTR &lt;50% than non-depressed patients (p&lt;0.0001). During follow-up, 4.83% of patients received the diagnosis of dementia within 3-years. The 3-year risk of dementia was highest for patients with a ≤50% TTR regardless of depression status (Figure). This rate was more than two times the rate of dementia compared to those without depression and with TTR&gt;75%. Conclusions: In patients managed for warfarin, depression is very prevalent and is associated with significant decreases in TTR. TTR appears to be the significant driver for increased 3-year dementia risk in these patients. Examining ways to improve TTR for patients with depression is warranted.
Body mass index and risk of dying from a bloodstream infection: A Mendelian randomization study
Authors: Tormod Rogne, Erik Solligård, Stephen Burgess, Ben M. Brumpton, Julie Paulsen, Hallie C. Prescott, Randi M. Mohus, Lise T. Gustad, Arne Mehl, Bjørn O. Åsvold, Andrew T. DeWan, Jan K. Damås
Journal: PLoS Medicine (2020)

Background In observational studies of the general population, higher body mass index (BMI) has been associated with increased incidence of and mortality from bloodstream infection (BSI) and sepsis. On the other hand, higher BMI has been observed to be apparently protective among patients with infection and sepsis. We aimed to evaluate the causal association of BMI with risk of and mortality from BSI. Methods and findings We used a population-based cohort in Norway followed from 1995 to 2017 (the Trøndelag Health Study [HUNT]), and carried out linear and nonlinear Mendelian randomization analyses. Among 55,908 participants, the mean age at enrollment was 48.3 years, 26,324 (47.1%) were men, and mean BMI was 26.3 kg/m 2 . During a median 21 years of follow-up, 2,547 (4.6%) participants experienced a BSI, and 451 (0.8%) died from BSI. Compared with a genetically predicted BMI of 25 kg/m 2 , a genetically predicted BMI of 30 kg/m 2 was associated with a hazard ratio for BSI incidence of 1.78 (95% CI: 1.40 to 2.27; p &lt; 0.001) and for BSI mortality of 2.56 (95% CI: 1.31 to 4.99; p = 0.006) in the general population, and a hazard ratio for BSI mortality of 2.34 (95% CI: 1.11 to 4.94; p = 0.025) in an inverse-probability-weighted analysis of patients with BSI. Limitations of this study include a risk of pleiotropic effects that may affect causal inference, and that only participants of European ancestry were considered. Conclusions Supportive of a causal relationship, genetically predicted BMI was positively associated with BSI incidence and mortality in this cohort. Our findings contradict the “obesity paradox,” where previous traditional epidemiological studies have found increased BMI to be apparently protective in terms of mortality for patients with BSI or sepsis.
Effects of different plasma expanders on rats subjected to severe acute normovolemic hemodilution
Authors: Guo-Xing You, Bing-Ting Li, Zhen Wang, Quan Wang, Ying Wang, Jing-Xiang Zhao, Lian Zhao, Hong Zhou
Journal: Military Medical Research (2020)

Abstract Background Plasma expanders are widely used for acute normovolemic hemodilution (ANH). However, existing studies have not focused on large-volume infusion with colloidal plasma expanders, and there is a lack of studies that compare the effects of different plasma expanders. Methods The viscosity, hydrodynamic radius (R h ) and colloid osmotic pressure (COP) of plasma expanders were determined by a cone-plate viscometer, Zetasizer and cut-off membrane, respectively. Sixty male rats were randomized into five groups with Gelofusine (Gel), Hydroxyethyl Starch 200/0.5 (HES200), Hydroxyethyl Starch 130/0.4 (HES130), Hydroxyethyl Starch 40 (HES40), and Dextran40 (Dex40), with 12 rats used in each group to build the ANH model. ANH was performed by the withdrawal of blood and simultaneous infusion of plasma expanders. Acid-base, lactate, blood gas and physiological parameters were detected. Results Gel had a lower intrinsic viscosity than HES200 and HES130 ( P &lt; 0.01), but at a low shear rate in a mixture of colloids, red cells and plasma, Gel had a higher viscosity ( P &lt; 0.05 or P &lt; 0.01, respectively). For hydroxyethyl starch plasma expanders, the COP at a certain concentration decreases from 11.1 mmHg to 6.1 mmHg with the increase of R h from 10.7 nm to 20.2 nm. A severe ANH model, with the hematocrit of 40% of the baseline level, was established and accompanied by disturbances in acid-base, lactate and blood gas parameters. At the end of ANH and 60 min afterward, the Dex40 group showed a worse outcome in maintaining the acid-base balance and systemic oxygenation compared to the other groups. The systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP) decreased significantly in all groups at the end of ANH. The DBP and MAP in the Dex40 group further decreased 60 min after the end of ANH. During the process of ANH, the Dex40 group showed a drop and recovery in SBP, DBP and MAP. The DBP and MAP in the HES200 group were significantly higher than those in the other groups at some time points ( P &lt; 0.05 or P &lt; 0.01). Conclusion Gel had a low intrinsic viscosity but may increase the whole blood viscosity at low shear rates. R h and COP showed a strong correlation among hydroxyethyl starch plasma expanders. Dex40 showed a worse outcome in maintaining the acid-base balance and systemic oxygenation compared to the other plasma expanders. During the process of ANH, Dex40 displayed a V-shaped recovery pattern for blood pressure, and HES200 had the advantage in sustaining the DBP and MAP at some time points.
Abstract 14594: Association Between Life's Simple 7 and Cardiovascular Disease in Cancer Patients Compared to Noncancer Controls in the Aric Cohort
Authors: Evelyn J Song, Sui Zhang, Ana E Prizment, Elizabeth J Polter, Elizabeth Selvin, Vijay Nambi, Corinne Joshu, Elizabeth Platz, Chiadi E Ndumele, Roberta Florido
Journal: Circulation (2020)

Introduction: Cancer survivors have greater cardiovascular disease (CVD) risk through unclear mechanisms. Little is known about whether Life’s Simple 7 (LS7) metrics differ between persons with and without cancer and if the link between LS7 and CVD is similar in cancer survivors compared to persons without prior cancer. Hypothesis: Persons who develop cancer have poorer LS7 metrics compared to noncancer controls, and an ideal LS7 score is less protective against CVD events in persons with versus those without prior cancer. Methods: A total of 2950 ARIC participants who developed cancer were matched at the time of cancer diagnosis (incidence density sampling) on age, sex, race, and study center, to 5900 noncancer controls. We compared LS7 metrics in individuals who developed cancer (assessed prior to cancer diagnosis) and in matched controls. We used Cox regression to evaluate the prospective association between LS7 score and CVD events (coronary heart disease, heart failure or stroke) stratified by cancer status, with test for interaction between LS7 and cancer. Results: Compared to matched noncancer controls, those who developed cancer were less likely to have an ideal smoking history, body mass index, glucose control, physical activity levels, and diet (defined by LS7 metrics; Table ). Overall those with cancer were less likely to have an ideal LS7 score than noncancer controls (18 vs 23% p&lt;0.0001). Compared to inadequate, an ideal LS7 score was similarly associated with lower CVD risk in persons with and without cancer (HRs 0.37 [95% CI: 0.26-0.52] and 0.40 [95% CI: 0.32-0.50], respectively), with no interaction between LS7 score and cancer status (p = 0.59). Conclusions: Individuals who develop cancer have poorer overall cardiovascular health as reflected by the LS7 score, but an ideal LS7 score is associated with similar cardio-protection in those with and without cancer. Cancer survivors may benefit from interventions targeting cardiovascular health metrics.
Nonviral Intercellular Adhesion Molecule-1 Small Interfering Ribonucleic Acid Sequences Transfection In Vivo: How Ultrasound Bursts Into Therapy⁎⁎Editorials published in the Journal of the American College of Cardiologyreflect the views of the authors and do not necessarily represent the views of JACCor the American College of Cardiology.
Authors: Christian Kupatt
Journal: Journal of the American College of Cardiology (2010)
Abstract 13513: Serial CT Surveillance of Abdominal Aortic Aneurysm Diameter Demonstrates Predominantly Linear Growth (N-TA <sup>3</sup> CT)
Authors: Sydney Olson, Marniker Wijesinha, Annalise Panthofer, William Blackwelder, Gilbert R Upchurch, Michael Terrin, John A Curci, Timothy T Baxter, Jon Matsumura
Journal: Circulation (2020)

Objective: Small abdominal aortic aneurysms (AAAs) have a low risk of rupture. Intervention is indicated when diameters exceed established thresholds. This study assessed the growth rates and patterns of AAAs over 2 years as documented on serial CT scans from the Non-Invasive Treatment of AAA Clinical Trial. Methods: 254 patients, 35 females with baseline AAA maximum transverse diameter (MTD) between 3.5-4.5 cm and 219 males with baseline MTD 3.5-5.0 cm, were included in this study. Linear regressions and segmental growth rates were used to model growth rates and patterns. Results: The yearly growth rates of AAA MTDs had a median of 0.17 cm/yr and mean of 0.19 cm/yr ± 0.14 (Figure 1). 10% of AAA displayed minimal to no growth (&lt; 0.05 cm/yr), 62% low growth (0.05-0.25 cm/yr), 28% high growth (&gt; 0.25 cm/yr). Baseline AAA diameter accounted for only 5.4% of growth rate variance (P&lt;0.001, R 2 0.05). Most AAAs displayed linear growth (70%); large variations in interval growth rates occurred infrequently (3% staccato growth, 4% exponential growth); a minority of subjects’ growth patterns were not clearly classifiable (11% indeterminate-not growing, 12% indeterminate-growing) (Figure 2). No patients with baseline MTD &lt; 4.25 cm exceeded sex-specific repair thresholds (males 0 / 92, [95% CI, 0.00-0.06]; females 0 / 25 [95% CI, 0.00-0.25]) in the course of follow-up for as long as two years. Conclusions: The majority of small AAAs exhibit linear growth; large intra-patient growth rate variations were infrequently observed over 2 years. AAA &lt; 4.25 cm can be followed with a CT scan in 2 years with little chance of exceeding interventional MTD thresholds of 5.5 cm for men.
OP0014 The acute phase response does not fully explain dyslipidemia and insulin resistance in inflammatory arthritis
Authors: PH Dessein, BI Joffe, AE Stanwix, Z Moomal
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> An increased frequency of insulin resistance (IR) and dyslipidemia has been identified in inflammatory arthritis (IA). These metabolic disturbances may be attributable to disease activity and therefore were implicated in the excess cardiovascular disease morality as reported in IA. <h3>Objectives</h3> In the present study we evaluated insulin sensitivity and lipid metabolism, as well as the potential role of the acute phase response as a predictor of these metabolic disturbances in IA. <h3>Methods</h3> Eighty seven patients (38 rheumatoid arthritis, 29 spondyloarthropathy, 20 undifferentiated inflammatory arthritis) and 30 age-, gender- and race matched healthy controls (CN) were enrolled. Patients who had taken glucocorticoids during the previous 2 months or were taking agents known to affect insulin sensitivity or lipid metabolism were excluded. The body mass index (kg/m<sup>2</sup>) was calculated in each subject. The erythrocyte sedimentation rate (ESR), plasma glucose, serum insulin and total cholesterol (chol), LDL-chol, HDL-chol and triglycerides were determined on fasting blood samples. IR was estimated by the homeostasis model assessment (HOMA). <h3>Results</h3> The mean (SD) BMI (kg/m<sup>2</sup>) was 26.5 (4.2) in the patients and 22.9 (2.8) in the CN (p &lt; 0.001). The mean (SD) HOMA (uU.mmol/ml.l) was 1.9 (1.3) in patients as compared to 1.1 (0.5) in CN (p = 0.001). The HDL-chol was lower (p = 0.002) and the total chol/HDL-chol was higher (p &lt; 0.001) in patients as compared to CN. Only after controlling for the BMI in addition to the ESR, was the HOMA no longer different between patients and CN. The ESR and HOMA, but not the BMI, significantly predicted (p &lt; 0.05) high chol/HDL-chol ratios. However, after controlling for these variables, this lipid parameter remained different in patients as compared to CN. Also, IA was associated with a positive family history for premature coronary arter disease (p &lt; 0.03). <h3>Conclusion</h3> Metabolic disturbances were identified in the majority of our patients and should therefore be addressed in the management of IA. IR could be attributed to the acute phase response and excess weight. However, dyslipidemia was associated with IA independent of the ESR, BMI and IR. Dyslipidemia may constitute a risk factor for IA. <h3>References</h3> Svenson KL, <i>et al</i>. Metabolism 1988;37:125–30 Park YB, <i>et al</i>. J Rheumatol. 1999;26:1701–4 Dessein PH, <i>et al</i>. Rheumatology 2001, in press
Abstract 14799: Scoring System for Post Ligation Cardiac Syndrome and Its Utility After Transcatheter and Surgical Patent Ductus Arteriosus Ligation in Extremely Low Birthweight Infants
Authors: Evan Harvey, Ranjit Philip, B. Rush Waller, Jason Johnson, Jorden Cunningham, Sandeep Chilakala, Mark Weems, Leah Apalodimas, Shyam Sathanandam
Journal: Circulation (2019)

Introduction: Patients undergoing ligation of a patent ductus arteriosus (PDA) experience post ligation cardiac syndrome (PLCS) with a reported incidence of 31-45%. Extremely low birth weight (ELBW...