tbuckley/cabot-search huggingface dataset:
COVID-19 in Multiple Myeloma Patients: Frequencies and Risk Factors for Hospitalization, Ventilatory Support, Intensive Care Admission and Mortality -Cooperative Registry from Grupo Brasileiro De Mieloma Multiplo (GBRAM)
Authors: Marcia Garnica, Edvan De Queiroz Crusoe, Glaciano Ribeiro, Rosane Bittencourt, Roberto José Pessoa Magalhães, Karla Richter Zanella, Abrahão Elias Hallack Neto, Juliana Lima, Caroline Sola, Emmanuella G Souza, Andre Magalhaes, Angelo Maiolino, Vania Hungria
Journal: Blood (2021)
Biomarkers of Vascular Inflammation for Cardiovascular Risk Prognostication
Authors: Alexios S. Antonopoulos, Andreas Angelopoulos, Paraskevi Papanikolaou, Spyridon Simantiris, Evangelos K. Oikonomou, Konstantinos Vamvakaris, Alkmini Koumpoura, Maria Farmaki, Marialena Trivella, Charalambos Vlachopoulos, Konstantinos Tsioufis, Charalambos Antoniades, Dimitris Tousoulis
Journal: JACC. Cardiovascular imaging (2021)
IMR-261, a Novel Oral Nrf2 Activator, Induces Fetal Hemoglobin in Human Erythroblasts, Reduces VOCs, and Ameliorates Ineffective Erythropoiesis in Experimental Mouse Models of Sickle Cell Disease and Beta-Thalassemia
Authors: Thiago Trovati Maciel, Caroline Carvalho, Rachel Rignault, Biree Andemariam, Betty S. Pace, Jennifer Isler OCain, Rahul Ballal
Journal: Blood (2021)
Sars-Cov-2 Antibody Decay Monitoring in mRNA Vaccinated Multiple Myeloma Patients
Authors: Samuel D. Stampfer, Marissa-Skye Goldwater, Bernard Sean S. Regidor, Scott Kristian Jew, Sean Elliott Bujarski, Haiming Chen, David Yashar, Ning Xu, Mingjie Li, Tracy Green, Eddie Fung, Elias Aquino, Regina Swift, Shahrooz Eshaghian, Aaron Feinstein, James R. Berenson
Journal: Blood (2021)
Abstract 9460: Effects of Milk Fat Globule Epidermal Growth Factor VIII on Adverse Aortic Remodeling in Mice With Advancing Age
Authors: Mingyi Wang, richard telljohann, Leng Ni, Wanqu ZHU, Soo hyuk Kim, Lijuan Liu, JING ZHANG, Kimberly McGraw, Robert Monticone, Christopher Morrell, Edward G Lakatta
Journal: Circulation (2021)

Background: Milk fat globule epidermal growth factor VIII (MFG-E8), a secreted membrane glycoprotein, is an inflammatory signaling molecule, promoting the proliferation and invasion of vascular smooth muscle cells in vitro. MFG-E8 also is a bridging molecule that connects vascular smooth muscle cells to elastic fibers, forming elastin-smooth muscle unit, an essential contractile element within arterial medial wall. The inflammatory effects of MFG-E8 signaling between cells and matrix on adverse arterial remodeling with advancing age, however, remains unknown. Methods and Results: In this study, homozygous MFG-E8 knockout (MFG-E8 KO, n=50) and age-matched wild type male mice (WT, n=50) were investigated. Western blot analysis confirmed that MFG-E8 protein was enriched in the aortic walls of WT mice, but not detected in MFG-E8 KO animals (Fig. A) . In WT, aortic MFG-E8 protein was markedly increased (~18-fold, p&lt;0.0001) in 96-week-old versus 40-week-old ( Fig. B ). Importantly, aortic elastin proportion (an index of elastin degradation) was significantly decreased in 96-week- versus 40-week-old while both collagen and calcium deposits proportion were markedly increased in WT mice; however, MFG-E8 deficiency significantly alleviated these age effects ( Fig. C ). The procalcification proteins alkaline phosphatase (ALP) and runt-related transcription factor 2 (Runx2) were markedly increased in 96-week-old WT versus MFG-E8 KO ( Fig. D ). Notably, MFG-E8 deficiency slightly effected on age-associated change in systolic blood pressure (SBP) compared to WT ( Fig. E) and significantly extended the lifespan compared to WT (p=0.032) ( Fig. F ). Conclusion: These findings suggest that MFG-E8 signaling links cells and matrix to age-associated adverse arterial remodeling, including elastin degradation, collagen deposition, and calcification. Thus, the MFG-E8 knockout has beneficial effects on arterial health during advancing age and prolongs the lifespan in mice.
VE-Cadherin Is Required for Cardiac Lymphatic Maintenance and Signaling
Authors: Natalie R. Harris, Natalie R. Nielsen, John B. Pawlak, Amir Aghajanian, Krsna Rangarajan, D. Stephen Serafin, Gregory Farber, Danielle M. Dy, Nathan P. Nelson-Maney, Wenjing Xu, Disha Ratra, Sophia H. Hurr, Li Qian, Joshua P. Scallan, Kathleen M. Caron
Journal: Circulation Research (2021)

Background: The adherens protein VE-cadherin (vascular endothelial cadherin) has diverse roles in organ-specific lymphatic vessels. However, its physiological role in cardiac lymphatics and its interaction with lymphangiogenic factors has not been fully explored. We sought to determine the spatiotemporal functions of VE-cadherin in cardiac lymphatics and mechanistically elucidate how VE-cadherin loss influences prolymphangiogenic signaling pathways, such as adrenomedullin and VEGF (vascular endothelial growth factor)-C/VEGFR3 (vascular endothelial growth factor receptor 3) signaling. Methods: Cdh5 flox/flox ;Prox1CreER T2 mice were used to delete VE-cadherin in lymphatic endothelial cells across life stages, including embryonic, postnatal, and adult. Lymphatic architecture and function was characterized using immunostaining and functional lymphangiography. To evaluate the impact of temporal and functional regression of cardiac lymphatics in Cdh5 flox/flox ;Prox1CreER T2 mice, left anterior descending artery ligation was performed and cardiac function and repair after myocardial infarction was evaluated by echocardiography and histology. Cellular effects of VE-cadherin deletion on lymphatic signaling pathways were assessed by knockdown of VE-cadherin in cultured lymphatic endothelial cells. Results: Embryonic deletion of VE-cadherin produced edematous embryos with dilated cardiac lymphatics with significantly altered vessel tip morphology. Postnatal deletion of VE-cadherin caused complete disassembly of cardiac lymphatics. Adult deletion caused a temporal regression of the quiescent epicardial lymphatic network which correlated with significant dermal and cardiac lymphatic dysfunction, as measured by fluorescent and quantum dot lymphangiography, respectively. Surprisingly, despite regression of cardiac lymphatics, Cdh5 flox/flox ;Prox1CreER T2 mice exhibited preserved cardiac function, both at baseline and following myocardial infarction, compared with control mice. Mechanistically, loss of VE-cadherin leads to aberrant cellular internalization of VEGFR3, precluding the ability of VEGFR3 to be either canonically activated by VEGF-C or noncanonically transactivated by adrenomedullin signaling, impairing downstream processes such as cellular proliferation. Conclusions: VE-cadherin is an essential scaffolding protein to maintain prolymphangiogenic signaling nodes at the plasma membrane, which are required for the development and adult maintenance of cardiac lymphatics, but not for cardiac function basally or after injury.
Pirtobrutinib, A Next Generation, Highly Selective, Non-Covalent BTK Inhibitor in Previously Treated CLL/SLL: Updated Results from the Phase 1/2 BRUIN Study
Authors: Anthony R. Mato, John M. Pagel, Catherine C. Coombs, Nirav N. Shah, Nicole Lamanna, Tahla Munir, Ewa Lech-Marańda, Toby A. Eyre, Jennifer A. Woyach, William G. Wierda, Chan Yoon Cheah, Jonathon B. Cohen, Lindsey E. Roeker, Manish R. Patel, Bita Fakhri, Minal A. Barve, Constantine S. Tam, David John Lewis, James N. Gerson, Alvaro J. Alencar, Chaitra S. Ujjani, Ian W. Flinn, Suchitra Sundaram, Shuo Ma, Deepa Jagadeesh, Joanna M Rhodes, Justin Taylor, Omar Abdel-Wahab, Paolo Ghia, Stephen J. Schuster, Denise Wang, Binoj Nair, Edward Zhu, Donald Tsai, Matthew S. Davids, Jennifer R. Brown, Wojciech Jurczak
Journal: Blood (2021)
Abstract 9555: A Mean Hemoglobin A1c Level of 7,5% is a Cliff Value for the Development of Cardiovascular Events in Diabetic Patients
Authors: Hirofumi Soejima, Takeshi Morimoto, Sadanori Okada, Chisa Matsumoto, Masafumi Nakayama, Hideaki Jinnouchi, Izuru Masuda, Masako Waki, Yoshihiko Saito, Hisao Ogawa
Journal: Circulation (2021)

Background: We sought to evaluate whether there was a difference in the incidence rate of cardiovascular event (CVD) among different hemoglobin (Hb) A1c levels in diabetic patients without a history of atherosclerotic events. Methods: The Japanese primary prevention of atherosclerosis with aspirin for diabetes (JPAD) trial was a multicenter, prospective, randomized, open label, blinded, end-point study done from 2002 to 2008. After completion of the JPAD trial, we followed up with the patients until 2019. We defined the cardiovascular events as the following: acute myocardial infarction; stable angina; unstable angina; sudden cardiac death; stroke; transient ischemic attack; aortic disease; and peripheral artery disease. Among 2,535 JPAD patients, HbA1c levels of the JPAD patients were recorded on average 8 times. Based on the mean value of HbA1c, we divided the patients into three groups: a High HbA1c Group (n=899, HbA1c ≥7.5%); a Moderate HbA1c Group (n=581, 7.5% &gt;HbA1c ≥7.0 %); or, a Low HbA1c Group (n=1055, 7.0% &gt;HbA1c). We compared the incidence of CVD among the three groups. Results: The mean HbA1c (%) was 8.6 in the High HbA1c Group, 7.4 in the Moderate HbA1c Group, and 6.6 in the Low HbA1c Group on registration. During an 11.56-year follow-up, the incidence of CVD was significantly higher in the High HbA1c Group (P&lt;0.0001, Figure) but was not significantly different between the Moderate HbA1c and the Low HbA1c Groups. Cox proportional hazards model analysis revealed that a High HbA1c level (HR, 1.61: 1.26-2.05, P=0.0001) was an independent factor after adjustment for proteinuria ≥±, age ≥65 years, male, body mass index ≥24 kg/m 2 , duration of diabetes ≥7.0% years, medications, eGFR ≥60 ml/min/1.73m 2 , and systolic blood pressure ≥140 mm Hg (Figure). Conclusions: Our study demonstrated that HbA1c ≥7.5% was independently associated with the incidence of CVD in diabetic patients without a history of atherosclerotic events while 7.5% &gt;HbA1c ≥7.0 % was not.
Impact of Platelet Transfusion on Pulmonary Function of Hematology Oncology Patients: The Piper Study
Authors: Allison P. Wheeler, Edward L. Snyder, Majed A. Refaai, Claudia S. Cohn, Jessica Poisson, Magali J. Fontaine, Mary Sehl, Ajay K. Nooka, Lynne Uhl, Philip C. Spinella, Maly Fenelus, Darla Liles, Thomas Coyle, Joanne Becker, Michael R. Jeng, Kathy Liu, Richard J Benjamin, Laurence Corash
Journal: Blood (2021)
Abstract 9479: Novel Predictors of Left Ventricular Reverse Remodeling in Patients With Recent-onset Dilated Cardiomyopathy Using T1 and T2 Mapping on Cardiac Magnetic Resonance
Authors: Ryo Yokoyama, Yumiko Kanzaki, Tomohiko Watanabe, Masaaki Hoshiga
Journal: Circulation (2021)

Introduction: The prognosis of patients with idiopathic dilated cardiomyopathy (DCM) has improved in recent decades with guideline-directed medical therapy. There is an essential need for better biomarkers to predict left ventricular reverse remodeling (LVRR) in DCM. Native T1, T2 and left ventricular (LV) global strain by cardiac magnetic resonance (CMR) without contrast agents provides a novel quantitative method for myocardial tissue characterization. Hypothesis: CMR parameters predict LVRR in patients with DCM. Methods: A total 34 patients ( 58 ± 13 years, 25 male) with DCM underwent baseline CMR imaging (3T Philips), including cine, late gadolinium enhancement (LGE) CMR, and triple-slice T1 and T2 mapping (short modified look locker inversion recovery ShMOLLI sequence). The 6SD-LGE (% area), global circumferential strain (GCS), global radial strain (GRS), global longitudinal strain (GLS), global radial strain (GRS), LV mass index (LVMI), LV end-diastolic volume (EDV), end-systolic volume (ESV) and ejection fraction (EF) were calculated from multiple short-axis views. Echocardiography was conducted before and &gt; 1 year after after optimal medical therapy. Results: The patients were divided into two groups, LVRR with LVEF increase of &gt;10% and the final value of ≥40% for those without. There were no significant differences in LV mass index, LVEDV, LVESV, and LVEF between the two groups (80 ± 20 g/m 2 vs 78 ± 19 g/m 2 ; 174 ± 54 ml vs 165 ± 48 ml; 134 ± 51 ml vs 122 ± 46 ml; 24 ± 9% vs 28 ± 9%, respectively). The any LV global strain showed no significant difference between the two groups. The 6SD-LGE, native T1, and T2 values were significantly lower in LVRR+ group than in LVRR-group (15.3 ± 15.5 % vs 5.9 ± 6.8%;1376 ± 59 ms vs 1301 ± 42 ms;55 ± 3.5 ms vs 50 ± 2.5 ms,respectively). The LGE-6SD &lt; 13%. native T1 value &lt; 1330 ms and T2 values &lt; 53ms were the best threshold values for predicting LVRR (The LGE-6SD: sensitivity, 82%; specificity, 41%; AUC 0.72, T1:sensitivity, 82%; specificity, 71%; AUC 0.87, and T2: sensitivity, 82%; specificity, 63%; AUC 0.88). Conclusions: Native T1 and T2 mapping values may be useful for assessing of the LVRR in patients with DCM even without contrast.
Chronically Elevated Interleukin-6 Disturbs the Coagulation Cascade in Mice
Authors: Tanja Knopp, Jeremy Lagrange, Rebecca Jung, Johannes Wild, Heidi Rossmann, Henri M.H. Spronk, Thomas Wunderlich, Nadine Hoevelmeyer, Thomas Münzel, Bernhard Lämmle, Wolfram Ruf, Philip Wenzel, Ari Waisman, Susanne Helena Karbach
Journal: Blood (2021)
Inhaled <i>β</i>2 Adrenergic Agonists and Other cAMP-Elevating Agents: Therapeutics for Alveolar Injury and Acute Respiratory Disease Syndrome?
Authors: Krishna Sriram, Michael B. Insel, Paul A. Insel
Journal: Pharmacological Reviews (2021)

Inhaled long-acting <i>β</i>-adrenergic agonists (LABAs) and short-acting <i>β</i>-adrenergic agonists are approved for the treatment of obstructive lung disease via actions mediated by <i>β</i>2 adrenergic receptors (<i>β</i>2-ARs) that increase cellular cAMP synthesis. This review discusses the potential of <i>β</i>2-AR agonists, in particular LABAs, for the treatment of acute respiratory distress syndrome (ARDS). We emphasize ARDS induced by pneumonia and focus on the pathobiology of ARDS and actions of LABAs and cAMP on pulmonary and immune cell types. <i>β</i>2-AR agonists/cAMP have beneficial actions that include protection of epithelial and endothelial cells from injury, restoration of alveolar fluid clearance, and reduction of fibrotic remodeling. <i>β</i>2-AR agonists/cAMP also exert anti-inflammatory effects on the immune system by actions on several types of immune cells. Early administration is likely critical for optimizing efficacy of LABAs or other cAMP-elevating agents, such as agonists of other Gs-coupled G protein–coupled receptors or cyclic nucleotide phosphodiesterase inhibitors. Clinical studies that target lung injury early, prior to development of ARDS, are thus needed to further assess the use of inhaled LABAs, perhaps combined with inhaled corticosteroids and/or long-acting muscarinic cholinergic antagonists. Such agents may provide a multipronged, repurposing, and efficacious therapeutic approach while minimizing systemic toxicity. <h3>Significance Statement</h3> Acute respiratory distress syndrome (ARDS) after pulmonary alveolar injury (e.g., certain viral infections) is associated with ∼40% mortality and in need of new therapeutic approaches. This review summarizes the pathobiology of ARDS, focusing on contributions of pulmonary and immune cell types and potentially beneficial actions of β2 adrenergic receptors and cAMP. Early administration of inhaled β2 adrenergic agonists and perhaps other cAMP-elevating agents after alveolar injury may be a prophylactic approach to prevent development of ARDS.
Nonmyeloablative Transplant for Sickle Cell Disease Does Not Lead to Kidney Dysfunction Post-HSCT
Authors: Emily Limerick, Santosh L. Saraf, Neal Jeffries, Farah O'Boyle, Clarissa Diamantidis, Yuliya Lokhnygina, Matthew M. Hsieh, Josu de la Fuente, Courtney D. Fitzhugh
Journal: Blood (2021)
Trial in Progress: A Multicentre, Parallel Arm, Open-Label Trial of Frontline R-CHOP/Polatuzumab Vedotin-RCHP and Glofitamab in Younger Patients with Higher Risk Diffuse Large B Cell Lymphoma (COALITION)
Authors: Adrian Minson, Nada Hamad, Costas K. Yannakou, Shu Min Wong, Jason P Butler, John F. Seymour, Michael Dickinson
Journal: Blood (2021)
Real-World Bleeding Outcomes, Weekly Factor Consumption Doses, Annualized Factor Costs in Severe-Type Patients with Hemophilia a (PwHA) before and after Switching to Extended Half-Life rFVIII-Fc Prophylaxis
Authors: Chia-Yau Chang, Shiue-Wei Lai, Mei-Mei Cheng, Pei-Yi Lai, Jung-Tzu Ku, Shu-Hsia Hu, Chen-Hua Tsai, Chao-Neng Cheng, Yen-Lin Liu, Jia-Ruey Tsai, Yeu-Chin Chen
Journal: Blood (2021)
Abstract 9320: Biological Sex as a Modifier of the Natural History of Dilated Cardiomyopathy
Authors: Upasana Tayal, Ruth Owen, Rachel Buchan, Brian Halliday, Amrit S Lota, Julian Jarman, Resham Baruah, James S Ware, Paul J Barton, John Cleland, Michael Frenneaux, Dudley J Pennell, John Gregson, Sanjay K Prasad
Journal: Circulation (2021)

Introduction: Dilated cardiomyopathy (DCM) has a ~20% 5-year mortality rate. Understanding the impact of biological sex offers scope to improve outcomes. Objective: Investigate potential sex specific differences in the outcome of DCM. Methods: Prospective longitudinal observational cohort study of 604 patients (n=206 women, 398 men) with DCM confirmed by cardiac MRI. The median follow up for cardiovascular death, major heart failure and arrhythmic events was 3.9 years. Results: At baseline women had higher left ventricular ejection fraction (LVEF), smaller left ventricular volumes, less myocardial fibrosis and lower serum troponin concentrations (all p&lt;0.05, Table 1), with no difference in age at study enrolment or medication. Despite this favourable profile, within 2 years women had more primary outcome events than men (Figure) with Kaplan Meier estimates of 10.7% vs 5.1%; adjusted* hazard ratio 3.47, 95% CI 1.81 to 6.65, [*age, LVEF, troponin, LMNA , left atrial volume and myocardial fibrosis]. Between 2-5 years, men and women had similar outcomes (adjusted* HR 0.55; 0.17,1.78). An LVEF &lt;35% in men (HR 3.21, 1.67 to 6.18, C-statistic 0.647) but &lt;40% in women (HR 2.37, 1.05 to 5.36, C statistic 0.602) had the greatest discrimination for predicting outcome. Conclusions: Female sex is an adverse modifier of the early natural history of DCM. There is evidence for sex specific risk stratification thresholds. Sex should be considered a determining variable in DCM care.
Drug-induced orthostatic hypotension: A systematic review and meta-analysis of randomised controlled trials
Authors: Cini Bhanu, Danielle Nimmons, Irene Petersen, Mine Orlu, Daniel Davis, Hajra Hussain, Sanuri Magammanage, Kate Walters
Journal: PLoS Medicine (2021)

Drug-induced orthostatic hypotension (OH) is common, and its resulting cerebral hypoperfusion is linked to adverse outcomes including falls, strokes, cognitive impairment, and increased mortality. The extent to which specific medications are associated with OH remains unclear.We conducted a systematic review and meta-analysis to evaluate the extent to which specific drug groups are associated with OH. EMBASE, MEDLINE, and Web of Science databases were searched from inception through 23 November 2020. Placebo-controlled randomised controlled trials (RCTs) on any drug reporting on OH as an adverse effect in adults (≥18 years) were eligible. Three authors extracted data on the drug, OH, dose, participant characteristics, and study setting. The revised Cochrane risk-of-bias tool for randomised trials (RoB 2) was used to appraise evidence. Summary odds ratios (ORs) were estimated for OH using fixed effects Mantel-Haenszel statistics. We conducted subgroup analysis on validity of OH measurement, drug dose, risk of bias, age, and comorbidity. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) tool was used to summarise the certainty of evidence. Of 36,940 citations, 69 eligible RCTs were included in the meta-analysis comprising 27,079 participants. Compared with placebo, beta-blockers and tricyclic antidepressants were associated with increased odds of OH (OR 7.76 [95% CI 2.51, 24.03]; OR 6.30 [95% CI 2.86, 13.91]). Alpha-blockers, antipsychotics, and SGLT-2 inhibitors were associated with up to 2-fold increased odds of OH, compared to placebo. There was no statistically significant difference in odds of OH with vasodilators (CCBs, ACE inhibitors/ARBs, SSRIs), compared to placebo. Limitations of this study are as follows: data limited to placebo-controlled studies, (excluding head-to-head trials), many RCTs excluded older participants; therefore results may be amplified in older patients in the clinical setting. The study protocol is publicly available on PROSPERO (CRD42020168697).Medications prescribed for common conditions (including depression, diabetes, and lower urinary tract symptoms) were associated with significantly increased odds of OH. Drugs causing sympathetic inhibition were associated with significantly increased odds of OH, while most vasodilators were associated with small nonsignificant differences in odds of OH, compared to placebo. Drugs targeting multiple parts of the orthostatic blood pressure (BP) reflex pathway (e.g. sympathetic inhibition, vasodilation, cardio-inhibitory effects) may carry cumulative risk, suggesting that individuals with polypharmacy could benefit from postural BP monitoring.
Mitochondrial temperature-responsive drug delivery reverses drug resistance in lung cancer
Authors: Lifo Ruan, Jun Chen, Chuanchao Du, Huiru Lu, Jiayu Zhang, Xiaomeng Cai, Rui Dou, Wenchu Lin, Zhifang Chai, Guangjun Nie, Yi Hu
Journal: Bioactive Materials (2021)

Reversal of cancer drug resistance remains a critical challenge in chemotherapy. Mitochondria-targeted drug delivery has been suggested to mitigate drug resistance in cancer. To overcome the intrinsic limitations in conventional mitochondrial targeting strategies, we develop mitochondrial temperature-responsive drug delivery to reverse doxorubicin (DOX) resistance in lung cancer. Results demonstrate that the thermoresponsive nanocarrier can prevent DOX efflux and facilitate DOX accumulation and mitochondrial targeting in DOX-resistant tumors. As a consequence, thermoresponsive nanocarrier enhances the cytotoxicity of DOX and reverses the drug resistance in tumor-bearing mice. This work represents the first example of mitochondrial temperature-responsive drug delivery for reversing cancer drug resistance.