tbuckley/cabot-search huggingface dataset:
THE ECOLOGICAL IMPACT OF COLONRECTAL SCREENING ON CLIMATE CHANGE: the experience of Reggio Emilia
Authors: A. Alberti, A. S. D'incà, P. Cecinato, M. Guberti, G. Iori
Journal: Endoscopy (2024)

Aims Climate change has been characterized as "the greatest threat to global health in the 21st century". The healthcare sector stands as one of the primary contributors to waste worldwide, accounting for approximately 4-5% of global CO2 emissions. Endoscopy ranks among the top three procedures in terms of overall waste production in countries such as the United States and England. Improper waste disposal poses a significant risk to the ecosystem. This study originates from the need to highlight the impact of endoscopies on climate change, specifically addressing the substantial waste generated by a common and fundamental practice like colorectal screening. Simultaneously, considering the pivotal role healthcare practitioners, particularly nurses, play in waste disposal, understanding the extent of their training becomes imperative. This assessment aims to evaluate the necessity of organizing training sessions within hospital facilities, specifically tailored to endoscopy—a small step toward an objective that is undeniably crucial for our future: making hospitals as environmentally sustainable as possible. Our aim is to investigate the ecological impact and weight of waste produced during colorectal screening in a month at the Endoscopy Department of Santa Maria Nuova Hospital in Reggio Emilia and to assess how adequate training on proper waste disposal enhances the behavior of nurses.
Abstract 9817: Krüppel-Like Factor 4 Integrates Immunometabolism of Human Arterial Endothelial Cells
Authors: Wusheng Xiao, Joseph Loscalzo
Journal: Circulation (2021)

Introduction: Inflammation and metabolic alterations are two common hallmarks of cardiovascular diseases. Yet, the molecular mechanisms integrating inflammation and cell metabolism remain elusive. Objective: We investigated whether Krüppel-like factor 4 (KLF4) serves as a link between cellular glucose metabolism and inflammation in human arterial endothelial cells. Methods and Results: Primary human pulmonary artery and aortic endothelial cells (PAEC and AoEC, respectively) were stimulated with tumor necrosis factor α (TNFα) or lipopolysaccharide (LPS). Results from fluorescent microscopy and Seahorse extracellular flux analysis revealed that TNFα and LPS enhanced glucose uptake by 2.2-fold, glycolysis by 2.3-fold, and mitochondrial respiration by 1.6-fold in PAEC and AoEC. The increase in glycolysis correlated with a 2-4-fold upregulation of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3) and PFKFB4, two key regulatory enzymes of glycolysis. Silencing PFKFB3 but not PFKFB4 entirely prevented TNFα-induced enhancement of glycolysis with a concomitant metabolic shift to mitochondrial respiration. Mechanistically, TNFα and LPS stimulated KLF4 mRNA and protein expression (2-4-fold), which functions as a transcriptional repressor of PFKFB3 . KLF4 knockdown potentiated TNFα-induced stimulation of PFKFB3 expression by 1.6-fold and glycolysis by 2.2-fold, effects which were completely prevented by co-silencing of PFKFB3 . Functionally, KLF4 silencing exacerbated TNFα-induced vascular cell adhesion molecule 1 (VCAM1) expression (by 2-3-fold), E-selectin secretion (by 2.8-fold), and monocyte adhesion (by 1.6-fold) in PAEC, all of which were attenuated by over 50% when PFKFB3 was inhibited by siRNA or with 3-(3-pyridinyl)-1-(4-pyridinyl)-2-propen-1-one (3-PO). By contrast, KLF4 overexpression-mediated inhibition of inflammation was significantly counteracted in PAEC with co-overexpression of PFKFB3 . Conclusion: These results indicate that KLF4 inhibits inflammation by normalizing PFKFB3-mediated enhancement of glycolysis and that the KLF4-PFKFB3 signaling axis integrates immunometabolism in human arterial endothelial cells.
Abstract 9852: Targeting Mek/Erk Signaling in the Treatment of Mitral Valve Prolapse
Authors: Tyler Beck, Jordan Morningstar, Cortney Gensemer, Kelsey Moore, Lilong Guo, Rachel Biggs, Reece Moore, Natalie Koren, Menny Benjamin, Ayesha Vohra, Andrew Harvey, Kendra Springs, Rupak Mukherjee, Kristi Helke, Russell A Norris
Journal: Circulation (2021)

Introduction: Mitral valve prolapse (MVP) is one of the most common forms of cardiac valve disease, affecting 1 in 40 humans and ~70% of small breed dogs. There are no effective nonsurgical treatments for MVP and therapeutic efforts have been hindered due to an incomplete understanding of its fundamental causes. Recent studies by our group have described the genetic basis for non-syndromic MVP and have provided new insights into molecular processes that underlie the disease. We have used this genetic information to identify druggable targets that can provide a non-surgical option for humans. In particular, we have identified the MEK/ERK pathway as the major disease initiating pathway and prolonged hyperactivation of MEK/ERK drives disease progression and severity. Hypothesis: Pharmacological blockade of MEK/ERK activities will sufficiently arrest the disease pathway and maintain the valves in a sub-clinical condition. Methods and Results: The FDA-approved MEK1 inhibitor Trametinib was administered to Dzip1 S24R/+ mice; a disease model that phenocopies human MVP. Preliminary results suggest safety concerns in mice associated with chronic administration of Trametinib (1 mg/kg/day). Animals demonstrated signs of cardiotoxicity on echocardiography, including left atrial enlargement; a reduction in E/A wave intensity; left ventricular wall movement abnormalities; prolonged isovolumetric relaxation time, and a reduced ejection fraction. As such, our lab has focused our efforts on identifying novel MEK1 inhibitors with a favorable safety profile. Utilizing a machine learning based workflow, we have identified highly selective MEK1 inhibitors with retained activity (&lt;100nM IC50 values); high gastrointestinal absorption (&gt;85%); favorable predicted LD50 values (&gt;1,000 mg/kg), and devoid of major cytochrome interactions. Conclusions: MEK1 may serve as a druggable target in the treatment of mitral valve prolapse; however, currently available MEK inhibitors demonstrate limiting toxicities. Future studies will involve in vivo administration of our novel compounds to Dzip1 S24R/+ mice. We envision results from this study will help guide the development of systemic or targeted therapies for the use in human patients with mitral valve prolapse.
Abstract 9022: Chronic Beta3-Adrenergic Receptor Antagonist Therapy Rescues Diabetic Cardiomyopathy Through Ca <sup>2+</sup> /Calmodulin-Dependent Protein Kinase II Inhibition in a Type II Diabetes Murine Model
Authors: Heng Cheng, Xiaoqiang Sun, Jing Cao, Zhe Chen, Yixi Liu, David M Herrington, David Zhao, Donald McClain, Dalane W Kitzman, Che Ping Cheng
Journal: Circulation (2021)

Background: Recent evidence showed that CaMKII inhibition with KN93 protects against diabetic cardiomyopathy (DCM). However, the off-target effects have limited its use. There are no CaMKII inhibitors available clinically. It may be best to use some complementary approaches for CaMKII inhibition. Previously we showed that diabetes produced upregulation of cardiac β 3 -AR-mediated inhibitory pathway promoting DCM progression. There is a significant crosstalk between β-AR signaling and CaMKII activation presenting CaMKII as a possible downstream mediator of detrimental β 3 -AR signaling in DCM. It is possible that the benefit of β 3 -AR antagonists (β 3 ANT) might involve modulation of CaMKII. We tested the hypothesis that chronic L-748-337, a selective β 3 ANT may inhibit CaMKII activity and limit DCM. Methods: LV myocyte CaMKIIδ expression and activity and myocyte function were determined in 3 groups (7/group) wild-type female mice over 14 weeks (W): Type 2 DM ( T2 ), 14 W fed high-fat diet (HFD), but after HFD for 4 W receiving streptozotocin (STZ, 40 mg/kg/day, i.p. 5 days); T2β 3 ANT , T2 mice at 10 W received L-748,337 (10 -7 M/kg/day, mini-pump) for 4 W; and Vehicle controls (C). Results: Versus C, T2 diabetes was induced in mice received HFD and low dose STZ with significantly elevated blood glucose. But only T2 myocytes had significantly increased protein levels of CaMKIIδ (T2: 29%, 0.53 vs C: 0.41) and CaMKIIδ phosphorylation (at Thr287) (PCaMKIIδ) (79%, 0.52 vs 0.29) followed by significantly reduced cell contraction (dL/dt max , 75 vs 134 μm/s), relaxation (dR/dt max , 60 vs 114 μ m/s) and [Ca 2+ ] iT (0.16 vs 0.21). The isoproterenol (ISO, 10 -8 M)-stimulated increases in dL/dt max (38% vs 58%), dR/dt max and [Ca 2+ ] iT (19% vs 30%) were also significantly reduced. By contrary, versus C, T2β 3 ANT myocytes had similar levels of CaMKIIδ (0.37) and PCaMKIIδ (0.31) with preserved cell contractility (131 μm/s), relaxation (109 μm/s) and [Ca 2+ ] iT (0.21). ISO caused increases in dL/dt max (57%), dR/dt max (52%) and [Ca 2+ ] iT (30%) were also closed to control values. Conclusions: Chronic β 3 ANT prevents Type II diabetes-caused upregulation of cardiac CaMKIIδ, thereby leading to the preservation of normal myocyte function, [Ca 2+ ] iT , and β-adrenergic reserve in a DCM murine model.
Abstract 6931: Epigenetic Modification of the Von Willebrand Factor Promotor Drives <i>in situ</i> Thrombosis in Chronic Thromboembolic Pulmonary Hypertension
Authors: Xue D Manz, Robert Szulcek, Xiaoke Pan, Petr Symersky, Chris Dickhoff, Jisca Majolée, Veerle Kremer, Elisabetta Michielon, Ekatarina S Jordanova, Teodora Radonic, Irene V Bijnsdorp, Sander R Piersma, Thang V Pham, Connie Jimenez, Frances S De Man, Reinier A Boon, Jan Voorberg, Peter L Hordijk, Jurjan Aman, Harm Bogaard
Journal: Circulation (2021)

Background: Chronic thromboembolic pulmonary hypertension (CTEPH) is characterized by thromboembolic obstructions of the pulmonary circulation; disease progression may involve in situ thrombosis. CTEPH patients have elevated Von Willebrand Factor (VWF) plasma levels and we hypothesized that endothelial secretion of VWF in CTEPH recruits platelets to the pulmonary vascular wall, thereby driving in situ thrombosis. Methods: CTEPH specific primary pulmonary artery endothelial cells (PAEC) were isolated from pulmonary endarterectomy material and control PAECs from patients undergoing lobectomy. Endothelial-platelet interaction was studied by an human in vitro model of thrombosis. We used an antibody and knockdown mediated approach to inhibit VWF and validate its functional relevance. Cell culture findings were validated in human tissue with immunofluorescence in situ hybridization, and proteomics and chromatin immunoprecipitation were used to investigate the underlying mechanism of CTEPH. Results: CTEPH-PAEC showed increased platelet adhesion compared to control. This was mediated by a 5-fold enhanced VWF gene expression, resulting in higher release of VWF protein upon endothelial activation. The increase in VWF mRNA was confirmed in human pulmonary artery tissue and was associated with elevated Nuclear Factor κB 2 (NFκB2) protein expression. Epigenetic histone modifications of reduced histone tri-methylation (H3K27Me3) and increased histone acetylation (H3K27Ac) of the VWF promotor in CTEPH-PAEC, support NFκB2 binding that drives VWF transcription. Knockdown of NFκB2 normalized VWF RNA expression levels and reversed the pro-thrombotic phenotype observed in CTEPH-PAEC. Conclusions: We show experimental evidence of VWF-mediated in situ thrombosis in CTEPH. Epigenetic modifications of the VWF promotor in CTEPH-PAEC, enhances NFκB2 binding and subsequently VWF transcription and platelet adhesion. We demonstrate a direct molecular link between inflammatory pathways and thrombosis in the pulmonary vascular wall that emphasizes the central role of in situ thrombosis in CTEPH.
Abstract 6943: Ablation Index-guided Pulmonary Vein Isolation Improve Performance and Safety of Treatment of Atrial Fibrillation
Authors: Cao Zou, Si-jia Sun, Ming-Sheng Hu
Journal: Circulation (2021)

Introduction: Pulmonary vein isolation (PVI) is a pivotal therapy for treatment of atrial fibrillation (AF), especially paroxysmal AF. Previous studies suggest that ablation index (AI) which integrated contact force (CF), time and power in a weighted formula improved success rate and safety of PVI. Hypothesis: Recently, our group has raised a novel protocol of AI-guided AF ablation according to different wall thickness of left atrium and compared the performance and safety of VisiTag ablation with or without this AI strategy. Methods: In this retrospectively study, AI parameters were set as 300-380U, 400-450U, 380-400U, 380-400U and 450-500U for posterior, anterior, inferior, roof and ridge respectively ( Figure 1 ). Radiofrequency energy was delivered at a maximum power output of 25-35 W depending on the ablation site (25-30W for the posterior aspects of the right and left PVs and 30-35 W for the anterior, inferior, Roof and ridge aspects). Results: No significant difference of patient characteristics was observed in VisiTag+AI group versus VisiTag group. One year after the procedure, the overall success rate was higher in VisiTag+AI group as compared to VisiTag group without differentiation of paroxysmal AF and persistent AF (95.1% vs. 83.3%, P=0.02). In subgroup analysis, the 1-year success rate in paroxysmal AF patients were 95.5% versus 82.5% in VisiTag+AI group versus VisiTag group (P=0.03), whereas the 1-year success rate in persistent AF patients were 93.3% versus 84.6% in VisiTag+AI group versus VisiTag group (P=0.40).Only one case of minor pericardial effusion without additional management was observed in VisiTag+AI group, whereas two cases of minor pericardial effusion and one case of pericardial tamponade were observed in VisiTag group during perioperative care. Conclusions: Improved performance and safety was observed in VisiTag ablation with this novel AI strategy in paroxysmal AF patients.
Abstract 9094: Intensive Lifestyle Medicine for Primary &amp; Secondary Prevention for Cardiovascular Risk Reduction in Patients With Diabetes
Authors: S. Hammad Jafri, Tasnim F Imran, Andrew M Freeman, Dean Ornish, Wen-chih Wu
Journal: Circulation (2021)

Introduction: Cardiovascular disease (CVD) carries significant morbidity and mortality, especially for patients with diabetes. Intensive Cardiac rehabilitation (ICR) has proven benefits for patients with CVD through a high fiber low fat diet, peer support, exercise and stress reduction; which may help in diabetes management. However, outcomes of ICR in patients with diabetes with and without CVD are unknown. Hypothesis: ICR can improve outcomes in diabetic patients with or without CVD. Methods: We conducted a retrospective cohort study of 4793 diabetic patients who were offered ICR at 46 CR centers across USA from January 2016 to December 2020. Five ICR centers in Hawaii had patients enrolled with diabetes without any CVD as Hawaii is the only state in US which has approved ICR for diabetic patients without CVD for primary prevention. ICR sessions are 4-hours long, twice weekly for 9-weeks of lifestyle modification aiming at high fiber low fat diet, peer support, exercise and stress reduction. Diabetic patients were divided into two groups: CVD group (known CVD) - 3723 patients (78%) and Non-CVD group (without CVD) - 1070 patients (22%). Primary endpoints were change in HbA1C, LDL and BP. Secondary outcomes were change in BMI, triglycerides, cholesterol, HDL, dietary fat intake, dietary fiber intake, depression scores (CESD) and exercise minutes per week. We used t tests to compare variables pre and post ICR. Results: The mean age of patients was 66.5 ± 0.2 years, 43% were females and 44% were white. ICR completion rate &amp; number of ICR sessions was higher in Non-CVD group (Non-CVD: 60.11 ± 27.16 vs. CVD: 55.67 ± 33.15, p&lt;0.01). Primary (HBA1c, BP, LDL) and secondary outcomes improved in both groups Pre and Post ICR as shown in table. Conclusions: Significant improvement in diabetes &amp; ICR outcomes were achieved for both groups after completing ICR. Although long term outcomes are unknown, diabetic patients should continue to participate in ICR for further risk reduction.
Abstract 14494: 5 Year Outcomes After Transcatheter &amp; Surgical Aortic Valve Replacements in Chronic Liver Disease Patients
Authors: Rahul Raiker, Haig Pakhchanian, Charles DeYoung, Arka Chatterjee
Journal: Circulation (2021)

Introduction: Chronic Liver Disease (CLD) patients are known to have increased morbidity and mortality when undergoing surgical procedures. While short term outcomes among patients undergoing transcatheter (TAVR) or surgical aortic valve replacement (SAVR) have been studied, research assessing long term outcomes are scant. Therefore, the goal was to assess 5-year complications among CLD patients undergoing TAVR or SAVR. Methods: A retrospective cohort study was done using TriNetX, a national federated real time database of 69 million records. Patient cohorts were identified if they met the criteria for CLD and underwent TAVR or SAVR up until May 2016 for 5 year follow up. An 1:1 matched propensity score analysis was conducted, adjusting for comorbidities and demographics, to calculate adjusted Risk Ratios (aRR) with 95% confidence intervals (CI) for complications of interest. Kaplan Meir (KM) analysis was done to calculate survival probability in 5 years among the 2 cohorts. Results: In a matched sample of 268 patients in each cohort, the TAVR group showed higher 5-year mortality (RR[CI]): (1.34[1.04-1.73]) compared to the SAVR Group. KM analysis also revealed a significantly lower survival probability in TAVR group (purple) compared to the SAVR group (green) (p&lt;0.001).There were no statistically significant differences among the 2 cohorts in other assessed long-term complications such as stroke (0.66[0.39-1.1]), new pacemaker placement (0.85[0.49-1.44]), and redo TAVR/SAVR (1.3[0.58-2.9]). Conclusions: In CLD patients, there is a higher risk of mortality for patients undergoing TAVR vs SAVR. All other assessed complications revealed no significant difference. Additional research is needed to visit further longer-term impacts in CLD patients.
Abstract 9092: Association of Biomarkers of Oxidative Stress, Inflammation, and Cardiac Damage with Long-Term Radiation-Induced Cardiovascular Outcomes in Breast Cancer
Authors: Alexi Vasbinder, Susan R Heckbert, Richard Cheng, Hilaire J Thompson, Oleg Zaslavsky, Rowan Chlebowski, Lisa Johnson, Rachel Yung, Jean Wactawski-Wende, Aladdin H Shadyab, Gretchen Wells, Lisa Warsinger Martin, electra paskett, Kerryn Reding
Journal: Circulation (2021)

Introduction: Radiation therapy (RT) is a common component of breast cancer (BC) management, but may be associated with radiation-induced cardiovascular disease (RICVD) which includes coronary heart disease, myocardial infarction, CVD death, heart failure, or stroke. We examined associations of biomarkers of oxidative stress (MPO, GDF-15, 8-OH-dG, PGF), cardiac injury (TnI, Cystatin-C), inflammation (IL-6, CRP), and myocardial fibrosis (TGF-B) with long-term RICVD in BC survivors. Methods: In an ancillary, nested case-control study within the Women’s Health Initiative, postmenopausal women with incident BC stages I-III, who received RT, and had pre- and post-BC diagnosis serum samples available not more than 3 years apart were eligible. Cases were defined as developing incident, physician-adjudicated coronary heart disease, myocardial infarction, CVD death, heart failure, or stroke after BC. Each case was matched to 3 controls on enrollment age and visit year of pre-BC blood draw. Biomarkers were analyzed using enzyme-linked immunosorbent assays and modeled as the post-BC to pre-BC ratio and log transformed to base 2. Logistic regression models were adjusted for demographic, lifestyle, and cancer characteristics. Results: A total of 55 cases and 158 controls were included with a mean (SD) age of 66.9 (5.5) years and a median (IQR) time from BC diagnosis to post-BC serum collection of 1.4 (0.7, 2.4) years. After adjustment, a higher 8-OH-dG ratio was significantly associated with an elevated risk of RICVD (Table). For a doubling in the biomarker ratio, RICVD risk was 3.04-fold higher (95% CI: 1.01, 9.21). Other biomarkers were not associated with RICVD risk. Conclusions: In this study, higher concentrations of 8-OH-dG were associated with a higher risk of RICVD. This suggests that oxidative DNA damage may be a putative pathway for delayed RICVD. However, given the sample size and multiple testing, further studies are needed to confirm or refute these findings.
Abstract 14269: The Association of Treadmill Exercise Test-Derived VO <sub>2</sub> Max and Symptomology in Athletes and Non-Athletes With Hypertrophic Cardiomyopathy
Authors: Ramin Garmany, J. Martijn Bos, Darrell B Newman, Jeffrey B Geske, Thomas G Allison, Steve R Ommen, Michael J Ackerman
Journal: Circulation (2021)

Introduction: Hypertrophic cardiomyopathy (HCM) is a major cause of sudden cardiac death in the young and especially in young athletes. The treadmill exercise test (TEST) has an important role in the functional assessment of patients with HCM. Herein, TEST-derived peak oxygen uptake (VO2 max) is a proxy for cardiopulmonary fitness. However, the correlation between symptoms and VO2 - especially in active young patients with HCM - is unclear. Objective: To explore the relationship between TEST-derived VO2 and symptomology in athletes and non-athletes with HCM. Methods: Overall, 91 patients (40% female) with HCM and a TEST with VO 2 data were included in this case-control study. Data were abstracted from the electronic health record using the first TEST performed at Mayo Clinic. Patients were defined as an athlete if they participated in an organized, competitive sport. Results: Overall, 60 HCM patients (33% female) were categorized as an athlete. HCM athletes were younger (17 vs. 27 years; p&lt;0.0001) and less likely to be symptomatic at the time of their TEST (OR=0.24; p=0.01). Additionally, athletes had a higher VO2 max (86% vs. 68% of predicted; p&lt;0.0001) and reached higher exercise times (93% vs 76% of predicted; p&lt;0.0001) compared to the non-athletes with HCM. When comparing symptomatic (n = 18) to asymptomatic patients (n = 73), symptomatic patients had i) a reduced exercise time (68% vs. 92% of predicted; p=0.002) and ii) lower VO2 max (62% vs 84% of predicted; p&lt;0.001). Finally, among the 27 patients (30%) with a VO 2 max &lt; 70% predicted (n=27), they i) more likely had a history of cardiac arrest (4 vs 0; p=0.006) and ii) were more likely to be symptomatic (OR=7.7; p&lt; 0.0001) than those with VO2 ≥ 70% of predicted (n=64). Importantly, however, 15/27 (56%) patients (8 athletes/7 non-athletes) with a VO2 max &lt; 70% were asymptomatic. Conclusions: Reduced exercise capacity is common in athletes with HCM and does not correlate with symptom status. However, if the TEST-derived VO2 max is &lt; 70%, treatment intensification may be necessary as it may portend an adverse outcome both arrhythmically and mechanically.