tbuckley/cabot-search huggingface dataset:
Abstract 10683: Association Between Triglycerides and Incident Chronic Kidney Disease in Diabetics Across Stages of Albuminuria
Authors: John Rizk, Melissa Soohoo, Leila Hashemi, Yousif Arif, Jui-Ting Hsiung, Maria Marroquin, Jessica Edward, Elani Streja
Journal: Circulation (2021)

Background: Hypertriglyceridemia, a component of the metabolic syndrome, is a known independent predictor of albuminuria and chronic kidney disease (CKD) in the general population. Urine albumin to creatinine ratio (UACR) and albuminuria are critical components in CKD staging as well as a hallmark of diabetic kidney disease. We sought to evaluate the relationship of triglycerides (TG) with incident CKD in diabetic non-CKD patients, stratified by level of albuminuria, which has been less studied thus far. Methods: This study comprised of 99,705 diabetic non-CKD veterans with data on TG and MetS components. The incident CKD outcome was defined as multiple eGFR measurements of &lt;60 mL/min/1.73m 2 at least 90 days apart. Using Cox proportional hazards models, we evaluated the association of TG with incident CKD, adjusted for case-mix characteristics, laboratory values including hemoglobin A1c, and stratified by baseline albuminuria categories. Results: The mean±SD age was 63±10, with a median [IQR] for TG of 147[99, 222] mg/dL, and UACR &lt;30 mg/g for 76% of patients. We observed a slight linear association between TG and incident CKD after adjustment for case-mix and laboratory variables among patients with Alb A1 and A2 stages (&lt;30 and 30-300 mg/g) (ref: TG 120-&lt;160 mg/dL) (Figure). While low TG were associated with a lower risk of incident CKD, elevated TG ≥240 mg/dL trended towards a higher risk of event. Among Alb A3 patients (&gt;300 mg/g), we observed an inverse U shape, where elevated TG ≥240 mg/dL trended towards a lower risk of incident CKD after adjustment. Conclusion: Elevated TG were associated with a higher risk of incident CKD in diabetic non-CKD patients with normal microalbuminuria. Patients with higher levels of albuminuria trended towards a lower relationship. Additional study is warranted to investigate the mechanism behind diabetic kidney disease risk with consideration for levels of albuminuria.
World Health Organization to begin negotiating international pandemic treaty
Authors: Luke Taylor
Journal: BMJ (2021)

World Health Organization states agreed on 1 December to begin negotiating an international agreement on how countries must prevent, prepare for, and react to pandemics.

The decision was made by WHO’s 194 member states, who convened in Geneva for the second ever special session of the World Health Assembly, and what senior WHO officials said was an inflection point in international public health.

The agreement is “a cause for celebration and cause for hope, which we will need,” said WHO’s director general, Tedros Adhanom Ghebreyesus. “Let it be said, decades from now when each of us is nothing more than photographs and memories, that we left the world a healthier, safer, fairer place than we found it.”

Member states have agreed to a timeline which could lead to a legally binding treaty tackling the global inequities and …
Abstract 13782: Platelet Aggregation and Adenosine Levels Among Patients With Stable Chronic Coronary Artery Disease Taking Ticagrelor or Prasugrel
Authors: Fernando Menezes, Remo Furtado, Talia Dalçóquio, Paulo Genestreti, Adriadne Bertolin, Luciano Baracioli, Marco Scanavini, beatriz oliveira, Andre Franci, Marli Silva, Alessandra Roggerio, Aline G Ferrari, Viviane Lima, Cesar Pereira, Carlos A Nakashima, Celia Strunz, Rocio Salsoso, Carla Soffiatti, Vanessa Baldo, Jose C Nicolau
Journal: Circulation (2021)

Introduction: Both, ticagrelor and prasugrel are important anti-ADP drugs, being superior to clopidogrel in patients with acute coronary syndromes (ACS). Whether those drugs have different effects among patients in the long run (&gt; 1 year) after ACS, however, is not completely understood. We therefore sought to directly compare the pharmacodynamic action of ticagrelor vs prasugrel in patients with chronic coronary artery disease (CCAD). Methods: This was a prospective, double blinded, randomized trial that compared platelet inhibition and adenosine levels with ticagrelor (180mg loading dose, followed by 90 mg BID) versus prasugrel (60mg loading dose, followed by 10 mg QD). Patient was eligible if suffered a documented episode of ACS at least 1 year before randomization, had age between 18 and 75 years, and was using aspirin 100 mg chronically. Platelet aggregation between groups was compared with the Multiplate ADP® assay, performed at baseline and after 15 days on study medication. Adenosine plasma levels were measured with high performance liquid chromatography at the same time points. Results: We randomized 87 patients (mean age 61,3 years, 83,9% with prior coronary angioplasty), being 40 allocated to ticagrelor and 47 to prasugrel. The study main results are described at Figure 1 (platelet aggregation) and Figure 2 (plasma adenosine levels). Conclusion: In stable patients after ACS, despite significant higher levels of adenosine plasma levels in the ticagrelor group, in comparison with the prasugrel group, similar levels of platelet inhibition were observed in both groups, suggesting that the role of adenosine in platelet aggregation is not an important one.
Abstract 12268: Overexpression of Endothelial p25 Causes Vascular Remodeling by Inducing Premature Aging
Authors: David Mondaca Ruff, Daniels Konja, Sandeep Singh, Yu Wang
Journal: Circulation (2021)

Introduction: Cardiovascular diseases are the leading cause of disability and death worldwide. The cyclin-dependent kinase 5 (CDK5) signaling pathway has been implicated in the regulation of SIRT1, a mammalian longevity regulator involved in the cellular homeostasis and aging. However, the participation of p25, the regulatory subunit of CDK5 in cardiovascular diseases has not been fully understood. Hypothesis: Selective overexpression of p25 in the vascular endothelium leads to vascular remodeling by accelerating vascular aging. Methods: A transgenic mouse model with selective overexpression of p25 in endothelial cells (EC-p25) was established. Aortas were collected from 12- or 30-weeks old EC-p25 and control mice. Vascular tone response, vascular senescence, aortic stiffness and aortic wall hypertrophy were evaluated with wire myography, senescence-associated β-galactosidase (SA-β-gal), alizarin red and heamatoxylin-eosine staining respectively. Protein levels were measured by Western blotting. Primary porcine aortic endothelial cells (PAECs) were transfected with p25, Sirt1 and Sirt1 lacking deacetylase activity, cell death and senescence were evaluated. Sirt1 activity was measured in EC-p25 and Control mice. A p-value p&lt;0.05 was considered as statistically significant. Results: Young EC-p25 mice exhibited increased vascular tone compared to the control mice. Alizarin red staining was more abundant in the aorta of 30 weeks old EC-p25 compared with the control mice, whereas SA-β-gal staining and aortic wall thickness were increased in EC-p25 mice. Overexpression of p25 in PAECs induced endothelial senescence and cell death. EC-p25 mice showed increased Sirt1 activity levels. Western blot analysis demonstrated that SIRT1 protein was fragmented in aorta of EC-p25 mice with increased levels of shorter fragments of Sirt1. PAECs transfected with Sirt1 mutant exhibited increased senescence. Conclusion: Selective overexpression of p25 in the vascular endothelium may regulate vascular remodeling by increasing vascular tone, vascular and endothelial senescence, aortic stiffness and aortic wall hypertrophy possible by modulating Sirt1 activity and integrity in the aorta of EC-p25 mice, accelerating premature vascular aging.
Abstract 9582: Maternal Triglyceride Levels Were Associated with Gestational Hypertension but Were Not Associated with Fetal Growth in Normal Pregnancy
Authors: Wei Hu, Ping Guan, Yanling Su
Journal: Circulation (2021)

Introduction: Abundant lipid supply and moderate mobilization of lipid metabolism allow proper nutrients for fetal development during pregnancy. However, knowledge of whether and how lipid levels associated with gestational hypertension and preeclampsia is inconsistent and no reference standards are currently defined for lipid parameters during pregnancy. Hypothesis: Higher maternal triglyceride (TG) levels were associated with pregnancy complications and that a wide range of TG levels was sufficient for fetal growth. Methods: A case-control study combined with a cross-sectional study. 464 patients with gestational hypertension and/or preeclampsia were pooled into a case group. A total of 1077 women with full-term pregnancies and no pregnancy complications were selected as controls. Results: Maternal levels of TG were significantly higher in the case group than in controls in all gestational weeks (12 to 16). Maternal levels of TG, total cholesterol (TC) and low-density lipoprotein (LDL-C) in healthy controls increased gradually and significantly with increasing gestational week, however, these lipid concentrations lost their steady elevating trends with gestational week increases in the case group. Binary logistic regression showed that TG is a risk factor associated with hypertension and/or preeclampsia at gestational weeks 12 to 16 and independent to maternal blood levels of glucose and LDL-C. The odds ratios for gestational complications were 2.24 [95% confidence interval (CI): 1.31 - 3.83], 2.11 (95%CI: 1.35 - 4.13), 2.61 (95%CI: 1.10 - 6.17), 2.45 (95%CI: 1.27 - 4.52) and 2.36 (95%CI: 1.17 - 4.32) respectively in case women with TG levels higher than the 75th percentile of healthy controls at gestational weeks 12 to 16. Of the healthy controls at gestational weeks 12 to 16, quantile regression showed that TG levels were not associated with real-time fetal growth measurements or final birthweight. The reference standards for maternal TG levels were estimated via the 10th, 25th, 50th, 75th, and 90th percentiles by gestational week. Conclusions: Maternal TG levels are associated with gestational hypertension and/or preeclampsia, and a wide range of TG levels is sufficient for fetal growth within a given gestational week.
Abstract 10964: Clinical Safety of Tadalafil in Patients Receiving Concomitant Antihypertensive Medication
Authors: Robert A Kloner, John B Kostis, Chunfu Qiu, Alankar Gupta, Thomas McGraw
Journal: Circulation (2021)

Introduction: It is important that physicians and patients are aware of the cardiovascular safety of options available to treat erectile dysfunction (ED)/benign prostatic hyperplasia (BPH) while on concomitant antihypertensive medications (AHM). Objective: This integrated safety analysis assessed the incidence of hypotension-related treatment-emergent adverse events (TEAEs) and major adverse cardiovascular events (MACE) in patients with concomitant use of tadalafil and AHM. Methods: Data were integrated from seventy-two Phase II-IV studies conducted on patients with a diagnosis of ED and/or BPH. Studies were categorized as either All placebo-controlled studies or All studies. The incidences of hypotensive-related TEAEs and MACE were analyzed by indication; by use of concomitant AHM; and by the number of concomitant AHM. Results: A total of 15,030 and 22,825 patients were included in the analyses for All placebo-controlled studies and All studies, respectively. In the All placebo-controlled studies, the incidence of hypotension-related TEAEs and MACE was ranging between 0.6-1.5% and 0.0-1.0%, respectively, across all indications and use of AHM. Tadalafil was associated with an increase in hypotension-related TEAEs only in the ED as-needed category not receiving any concomitant AHM (p-value=0.0070); no difference was reported between placebo and tadalafil in all indication categories of patients receiving ≥1 AHM (p-value≥ 0.7386). Similarly, no differences (p-value≥ 0.2238) were observed in the incidence of MACE between tadalafil and placebo treatment groups, with or without concomitant use of AHM, and across all indication categories. In the All studies results were similar. Conclusion: The concomitant use of tadalafil alongside AHM did not increase the risk of hypotension-related TEAEs or MACE compared with AHM alone. Figure Odds ratio of incidences of hypotension-related TEAEs between placebo and tadalafil groups by number of concomitant AHM
Abstract 11747: Meta-Analysis on Left Atrial Appendage Closure for Atrial Fibrillation During Cardiac Surgery
Authors: Rohan M Prasad, Yehia Saleh, Abdullah Al-abcha, Mohammad Fahad F Salam, Ola Abdelkarim
Journal: Circulation (2021)

Introduction: The current guidelines indicate that left atrial appendage (LAA) excision or exclusion during cardiac surgery has a class IIA recommendation for atrial fibrillation. However, the short- and long-term side effects are not well reported or defined. Methods/Results: We conducted a meta-analysis of all studies that compared LAA exclusion during cardiac surgery in patients with AF compared to a placebo arm. Five randomized controlled trials (RCTs) and 23 observational studies were included with a total of 540,111 patients. In regards to postoperative stroke/embolic events, the LAA exclusion group had a significantly decreased risk (risk ratio [RR] 0.75; 95% confidence interval [CI] 0.64 to 0.87; p=0.0002, I2=0%). This significantly reduced risk of stroke/embolic events for the LAAC arm was also seen in both the perioperative period (RR 0.82, 95% CI 0.69 to 0.96, p=0.01, I2=41%) and when follow-up was greater than two years (RR 0.70, 95% CI 0.57 to 0.85, p=0.0003, I2=39%). In terms of all-cause mortality, there was no significant difference for the LAA exclusion group in the early perioperative period (RR 0.84, 95% CI 0.56 to 1.28, p=0.42, I2=85%); however, it was significant after a follow-up of greater than two years (RR 0.81, 95% CI 0.68 to 0.97, p=0.02, I2=79%). Conclusion: This meta-analysis illustrates a significantly decreased risk of postoperative stroke/embolic events in the perioperative period and after a follow-up period greater than two years. Although the early postoperative all-cause mortality did not show a significant difference between the two groups, there was a significant decreased risk in the LAA excision group after a follow-up duration of two years.
Assessing the Immune Tumour Microenvironment (iTME) Using Multiplex Immunoflourescence Histochemistry (mIHC) Demonstrates Close Proximity of Cytotoxic T-Cells to Plasma Cells (PC) in Patients with Newly Diagnosed Multiple Myeloma (NDMM)
Authors: Slavisa Ninkovic, Louise E. Purton, Simon J Harrison, Hang Quach
Journal: Blood (2021)
Abstract 13075: Initial Physical Activity Level is a Strong Predictor of Adherence to the Physical Activity Goal: A Secondary Analysis of the SMARTER Weight Loss Trial
Authors: Zhadyra Bizhanova, Susan M Sereika, Jacob K Kariuki, Margaret B Conroy, Maria M Brooks, Bonny Rockette-Wagner, Jessica Cheng, Britney Beatrice, India Loar, Yuhan Wang, I Wayan I Pulantara, Bambang Parmanto, Maribel Cedillo, Lora E Burke
Journal: Circulation (2021)

Background: Over a third of excess coronary heart disease mortality in the US is related to inadequate physical activity (PA). Use of wearable activity trackers is beneficial for PA improvement in many populations. However, predictors of long-term adherence to PA remain unknown. Hypothesis: The 1 st week PA levels will be the strongest predictors of long-term adherence to the PA goal in adults with overweight or obesity in a mHealth weight loss intervention trial. Methods: A secondary analysis of a 12-month behavioral weight loss trial (SMARTER) that randomized 502 participants to either self-monitoring with tailored feedback messages (SM+FB, n=251) or self-monitoring alone (SM, n=251) was conducted. At baseline, each participant received a Fitbit Charge 2 and PA goal of ≥150 minutes of moderate or vigorous activity (MVPA) per week. The outcome of interest for this analysis was long-term PA adherence, i.e., the number of weeks adherent to PA goal over 12 months. Twenty-six explanatory variables were considered, including treatment assignment; baseline socio-demographics; health history; body mass index (&lt;30 vs. ≥30 kg/m 2 ); psychosocial factors; and1 st week PA levels (&lt;150 vs. ≥150 MVPA min/week). Machine learning methods (i.e., random forest regression trees and lasso regression) were used to identify predictors of long-term PA adherence. Results: The sample ranged in age from 19 to 75 years (57% were &lt;50 years old), and was mostly Caucasian (83%), female (80%) and had a mean BMI 33.7 ± 4.0 kg/m 2 . The sample was randomly split 4:1 into training (n=394) and validation subsamples (n=104) which were comparable by treatment assignment. Both random forest and lasso regression identified 1 st week PA levels as the most important predictor of long-term PA adherence. The findings were confirmed in the validation cohort with an out-of-sample R-square of 40.2% from random forest and a R-square of 47.9% from lasso regression, suggesting good predictive abilities. Conclusion: This analysis confirmed higher initial PA levels as the strongest predictor of long-term PA adherence. The findings support screening for PA at study entry and developing tailored interventions for those with lower initial PA levels.
Child, maternal, and adult mortality in Sierra Leone: nationally representative mortality survey 2018–20
Authors: Ronald Carshon-Marsh, Ashley Aimone, Rashid Ansumana, Ibrahim Bob Swaray, Anteneh Assalif, Alimatu Musa, Catherine Meh, Francis Smart, Sze Hang Fu, Leslie Newcombe, Rajeev Kamadod, Nandita Saikia, Hellen Gelband, Amara Jambai, Prabhat Jha
Journal: The Lancet Global Health (2021)

Sierra Leone's child and maternal mortality rates are among the highest in the world. However, little is known about the causes of premature mortality in the country. To rectify this, the Ministry of Health and Sanitation of Sierra Leone launched the Sierra Leone Sample Registration System (SL-SRS) of births and deaths. Here, we report cause-specific mortality from the first SL-SRS round, representing deaths from 2018 to 2020.
Abstract 12607: Long-Term Outcomes of CABG versus Medical Therapy: A Systematic Review and Meta-Analysis of 34350 Patients With Ischemic Heart Diseases
Authors: Nso Nso, KELECHI EMMANUEL, Mahmoud Nassar, Milana Zirkiyeva, Khushal Choudhary, Sostanie Enoru, Vincent Rizzo, MOST S MUNIRA, Jonathan Marmur, Farshid Radparvar
Journal: Circulation (2021)

Background/Aim: Medical therapy (MT) and coronary artery bypass graft (CABG) are valuable treatment options for patients with ischemic heart diseases (IHD). However, their negative outcomes in the long-term are poorly investigated. Therefore, we conducted this meta-analysis to determine the long-term effects of both interventions. Methods: Till Nov 27, 2020, nine databases were searched for original articles investigating MT versus CABG in patients with IHD. Primary outcomes included mortality, survival, revascularization/additional treatment, event-free survival (incidence of cardiovascular (CV) mortality, myocardial infarction (MI), or refractory angina), cerebrovascular accidents (CVA), and acute MI. Secondary outcomes included imaging findings, such as left ventricular ejection fraction (LVEF). Cochrane’s revised tool (Version II) and ROBINS-I tool were used to assess the risk of bias of randomized and non-randomized intervention studies, respectively. Results: Fifteen studies were included in the systematic review, while twelve studies (34350 patients) were analyzed. CABG was associated with a significant reduction in all-cause mortality (OR=0.61; 95%CI: 0.45-0.83) and significant improvement in survival (OR=2.45; 95%CI: 1.61-3.73). The risk of acute MI (OR=0.44; 95%CI: 0.23-0.85) and the need for revascularization/additional treatment were significantly lower in the CABG group. No significant differences were noted as regards CV mortality (OR=0.64; 95%CI: 0.34-1.17), CVA (OR=1.45; 95%CI: 0.56-3.75), event-free survival (OR=0.86; 95%CI: 0.22-3.39), and LVEF (OR=-0.21; 95%CI: -1.48-1.6). Eleven studies had low risk, and four studies had a high risk of bias. Conclusions: Compared to medical therapy alone, CABG offers better long-term outcomes in terms of fewer mortality rates, higher survival rates, and limited need for revascularization or additional treatment.
A Phase II Study of Azacitidine, Venetoclax and Trametinib in Relapsed/Refractory AML Harboring a Ras Pathway-Activating Mutation
Authors: Sai Prasad Desikan, Farhad Ravandi, Naveen Pemmaraju, Marina Konopleva, Sanam Loghavi, Gautam Borthakur, Elias J. Jabbour, Naval Daver, Nitin Jain, Kelly S. Chien, Abhishek Maiti, Guillermo Montalban-Bravo, Tapan M. Kadia, Monica Kwari, Hagop Kantarjian, Nicholas J. Short
Journal: Blood (2021)
BIOM-31. ERK1/2 PHOSPHORYLATION PREDICTS SURVIVAL FOLLOWING ANTI-PD-1 IMMUNOTHERAPY IN RECURRENT GLIOBLASTOMA
Authors: Víctor Arrieta, Andrew X Chen, J Robert Kane, Seong Jae Kang, Cynthia Kassab, Crismita Dmello, Junfei Zhao, Kirsten Burdett, Pavan Upadhyayula, Catalina Chang, Joseph Shilati, Dinesh Jaishankar, Li Chen, Andrew Gould, Daniel Zhang, Jinzhou Yuan, Wenting Zhao, Xiaoyang Ling, Jared K Burks, Brice Laffleur, Christina Amidei, Jeffrey N Bruce, Rimas V Lukas, Jonathan T Yamaguchi, David Cieremans, Gerson Rothschild, Uttiya Basu, Matthew McCord, Daniel Brat, Hui Zhang, Lee A D Cooper, Bin Zhang, Peter Sims, Timothy Cloughesy, Robert Prins, Peter Canoll, Roger Stupp, Amy B Heimberger, Craig Horbinski, Fabio Iwamoto, Raul Rabadan, Adam M Sonabend
Journal: Neuro-Oncology (2021)

Abstract PD-1 checkpoint inhibition has led to remarkable clinical responses in several cancer types. Whereas PD-1 blockade has not shown an overall survival (OS) benefit for glioblastoma (GBM) patients, a subset of them exhibit long-term responses to this immunotherapy. Previously, we reported an enrichment of BRAF/PTPN11 activating mutations in 30% of recurrent GBMs that responded to PD-1 blockade, but the molecular profile of the majority of responders remained elusive. Given that BRAF and PTPN11 promote MAPK/ERK signaling, we investigated whether activation of this pathway is associated with response to PD-1 inhibitors in recurrent GBM, including patients that do not harbor BRAF/PTPN11 mutations. Immunohistochemistry for ERK1/2 phosphorylation (p-ERK), a marker of MAPK/ERK pathway activation, was performed in a discovery cohort including pre-treatment specimens of 29 recurrent GBM patients treated with adjuvant PD-1 blockade, and 33 patients who did not undergo immunotherapy. p-ERK was predictive of response and OS following PD-1 blockade. Yet p-ERK was not associated with OS in patients not treated with immunotherapy. p-ERK was also associated with OS in a validation GBM cohort treated with adjuvant anti-PD-1 therapy. Single-cell RNA-seq and multiplex-immunofluorescence analyses revealed that p-ERK was mainly localized in tumor cells and high p-ERK GBMs contained tumor-infiltrating myeloid cells and microglia with elevated expression of MHC class II and associated genes. Thus, our findings indicate that ERK1/2 activation in recurrent GBM is predictive of response to PD-1 blockade and is associated with a distinct myeloid cell phenotype.
Serum Albumin and Neutrophil-to-Lymphocyte Ratio, Two Independent Factor Predicting Survival in Patients with Follicular Lymphoma: A Multi-Institutional Retrospective Cohort of 741 FL, from the Latin American Lymphoproliferative Study Group (GELL)
Authors: Marialejandra Alejandra Torres Viera, Luis Villela, Brady E Beltran, Denisse Castro, Myrna Candelaria, Henry Idrobo, Victoria Otero, Alana Von Glasenapp, Fabiola Valvert, Sally Rose Paredes, Juan Barrios, Ana Florencia Ramirez-Ibarguen, Camila Peña, Maria Elena Cabrera, Claudia Gajardo, Macarena Roa, Catalina Díaz, Lorena Fiad, Carlos Best, Maria Prates, Juan Alejandro Ospina, Laura Silva Idárraga, Humberto Martinez, Melani Otañez, Maria Alejandra Luna, Carmen Lome, Fernando Pérez-Jacobo, Rosio Baena, Jose Macias, Nancy Cristaldo, Guilherme Fleury Perini, Larissa Lane Cardoso, Rosa Oliday Rios, Yusaima Rodriguez, Bryan Valcarcel, Jorge J. Castillo, Luis Malpica Castillo
Journal: Blood (2021)