tbuckley/cabot-search huggingface dataset:
Abstract 13469: Novel Role of Extracellular SOD-derived H <sub>2</sub> O <sub>2</sub> Signaling in Exercise-induced Vascular Adaptation in Type 2 Diabetes
Authors: Sudhahar Varadarajan, Kareem Abdelsaid, Malgorzata McMenamin, Xuexiu Fang, Yali Hou, Masuko Ushio-fukai, Tohru Fukai
Journal: Circulation (2020)

Background: Exercise training promotes vascular adaptation (restoration of endothelial function and angiogenesis) in type2 diabetes (T2D). Since eNOS uncoupling/O 2 - are increased in T2D, exercise may promote vascular adaptation via mechanism other than eNOS-NO axis. Extracellular superoxide dismutase (ecSOD) is a secreted copper (Cu) containing SOD that catalyzes the dismutation of O 2 - to H 2 O 2 and its full activity requires Cu transporter ATP7A. We reported that ATP7A-ecSOD pathway is reduced in T2D and that ecSOD-derived H 2 O 2 promotes VEGFR2 signaling and angiogenesis in endothelial cells. However, role of ATP7A-ecSOD axis and H 2 O 2 signaling in vascular adaptation to exercise in T2D have not been reported. Oxidation of Cysteine residues of targets proteins to generate cysteine sulfenic acid (Cys-OH) is a key initial event in H 2 O 2 -mediated signaling. Results: Here we show that ATP7A protein (49%), ecSOD activity (51%) and extracellular H 2 O 2 levels in blood vessels and skeletal muscles were significantly decreased in high fat diet-induced T2D mice compared to control C57Bl6 mice, which were rescued by volunteer wheel exercise (2 weeks) or in T2D/ATP7A overexpressing mice. In parallel, exercise training restored impaired endothelium-dependent relaxation (EDR) of resistant arteries and angiogenesis (CD31+ capillary, 2.4-fold) in skeletal muscle of T2D mice, which were inhibited by exogenous catalase or in T2D/ecSOD KO mice, but not by L-NAME, suggesting that ecSOD-derived H 2 O 2 , but not eNOS/NO, mediates exercise-induced beneficial effects. Mechanistically, exercise significantly increased Cys-OH formation of PKG1α (2.3-fold), which was shown to induce EDR in H 2 O 2 -, but not NO/cGMP-, dependent manner, in T2D vascular tissues as well as Cys-OH formation of AMPK (3.6-fold) and AMPK downstream angiogenic PGC1α and VEGF protein expression in T2D skeletal muscles. Of note, these exercise-induced Cys oxidation of PKG1α and AMPK were not observed in control or T2D/ecSOD KO mice. Conclusion: Exercise-induced ATP7A-ecSOD axis-mediated out-side in H 2 O 2 signaling plays an important role in promoting vascular adaptation in T2D via Cys oxidation of redox-sensitive kinases required for endothelial function and angiogenesis in skeletal muscles.
Abstract 14334: Best Electrocardiographic Criteria for Hyperkalemia in Chronic Hemodialysis Patients
Authors: Saima Shikari, Keith Bartolomei, Daniel Landry, John Marenco, Gregory Braden
Journal: Circulation (2020)

Introduction: To date, the effects of hyperkalemia (HK) on the ECG in chronic hemodialysis (HD) patients are inconsistent. No studies examining all of the possible effects of HK on the ECG of HD patients have been performed. We studied the ECGs of 128 consecutive HD patients with acutely clotted grafts or fistulas. ECGs from 46 HK patients with potassium levels ≥5.5 mEq/L were compared to 82 patients with normal potassium (NK) levels &lt; 5.5 mEq/L. Methods: Patients with bundle branch block or cardiac events within 3 months were excluded. There were no differences between HK &amp; NK patients for dialysis duration, causes of ESRD, cardiac disease or serum levels of Na + , Ca 2+ , HCO3, or phosphorus. ECG analysis included: height &amp; width of P waves, T waves in V4 &amp; Lead II, time intervals of PR, QRS, QT, QTc, PR/QT, PR/QTc &amp; slopes of ascending &amp; descending T waves in Lead II &amp; V4. For the first time ever in HK HD patients, the ECG measurements in 32 HK patients were compared to their own NK ECGs obtained 3 to 6 months from the HK event. Results: Univariate analysis between the 46 HK &amp; 82 NK patients showed 4 differences in mean values: V4 T wave height 4.0 vs 2.9mm, Lead II T wave height 2.7 vs. 2.0 mm, &amp; V4 T wave ascending (.03 vs .02) &amp; descending slopes (.04 vs .03). Multivariate analysis for all clinical &amp; ECG findings between HK &amp; NK patients found only the increased height of the T wave in V4 was significant, p&lt;0.05. In contrast, the ECG analysis of the HK patients to their NK ECGs revealed more differences: higher T wave height in V4 (5.0 vs 3.7mm), higher T wave height in Lead II (4.0 vs 2.7 mm), shorter width of T wave in V4 (2.4 vs 4.1ms) &amp; Lead II (2.1 vs 4.1ms), longer PR (188 vs 167ms) &amp; steeper slopes in the T waves in Leads II &amp; V4. Regression analysis of the change in potassium from NK to HK to each ECG measurement above showed that the only significant correlation was to the width (r= -.433, p= .007) &amp; height (r= .333, p=.03) of the T wave in V4. In these HK HD patients T wave tenting in V4 was present in 56%. Conclusion: Intra-patient comparison of baseline NK to HK ECGs in HD patients confirms the importance of the height of the T wave in Lead V4 to diagnose HK. Shortened width and increased height of T waves in V4 are the most predictive ECG changes of HK.
Abstract 16860: Racial Disparity in COVID-19 Patients With Concomitant Myocardial Injury
Authors: Brian C Case, Charan Yerasi, Brian Forrestal, Chava Chezar Azerrad, Lowell F Satler, itsik ben-dor, Hayder Hashim, Nelson L Bernardo, Ron Waksman
Journal: Circulation (2020)

Introduction: Cardiac involvement in Coronavirus Disease 2019 (COVID-19) is common. Estimated that 30% of patients hospitalized with COVID-19 have an elevated troponin and these patients have worse prognosis when compared to patients without myocardial injury. Hypothesis: The purpose of this study is to investigate if there is any racial disparity in the in-hospital clinical outcomes of COVID-19 patients with myocardial injury. Methods: This study included all COVID-19 positive patients within the MedStar Health System (11 acute hospitals in the DC/Maryland/Virginia area) with an elevation of troponin and a diagnosis of either ST-Elevation Myocardial Infarction (STEMI) or Non-ST-Elevation Myocardial Infarction (NSTEMI) based on International Classification of Diseases-10. Results: There was 3,589 COVID-19 admissions between March to June 2020. Of these, a total of 75 COVID-19 patients had either a STEMI or NSTEMI. Overall mean age was 70.9 ± 14.6 and 54.7% were male. Of these patients, the majority were African American (51; 68%) followed by Caucasians (15; 20%). The overall in-hospital mortality rate was 24.3%, with African Americans having a higher rate (73.7%) as compared to Caucasians (15.8%) p 0.05. Furthermore, African Americans trended toward having higher rates of intensive care unit (ICU) admissions, intubation, and longer ICU stays; however, not statistically significant. Despite African Americans appearing to be a sicker cohort, inflammatory markers and myocardial involvement did not differ between the two groups (Table 1). Conclusions: Patients with COVID-19 and concomitant myocardial injury have a high in-hospital mortality rate. There is a racial disparity with African Americans having a higher rate of in-hospital mortality. However, inflammatory markers and myocardial injury does not differ between the two groups meaning other unidentified underlying issue may be the etiology for a sicker cohort in African Americans.
Abstract 12881: Noninvasive <i>In Vivo</i> Assessment of Cardiac Metabolism in Dobutamine-stressed Ischemic Rat Hearts Using Hyperpolarized <sup>13</sup> C MRI
Authors: Gaurav Sharma, Alexander Funk, Xiaodong Wen, Crystal Harrison, Nesmine Maptue, A. Dean Sherry, Chalermchai Khemtong, Craig R Malloy
Journal: Circulation (2020)

Introduction and Hypothesis: Conventional metabolic imaging methods such as PET, dobutamine stress echo or late gadolinium enhancement do not directly detect the functional state of the critical organelle in oxidative metabolism, the mitochondrion. Hyperpolarized (HP) 13 C-metabolic imaging has been used to assess mitochondrial function in preclinical models and is an exciting new imaging method for evaluating the ischemic myocardium noninvasively. This study aims to evaluate myocardial response to dobutamine stress in ischemic rat hearts using HP-[1- 13 C]pyruvate. Methods: Metabolism of HP[1- 13 C]pyruvate was investigated in male SD rats in four groups: 1. normal myocardium (NM), 2. ischemic myocardium (IM), 3. NM+dobutamine, 4. IM+dobutamine. The myocardial ischemic model was developed by partial occlusion of the coronary artery as described in earlier studies by others. For dobutamine stress HP-MRS, intra-peritoneal injection of 1.5 mg/kg of dobutamine was administered before positioning the animal in the MRI scanner. 13 C data were acquired 7 days after the surgery in a 4.7 T MRI scanner using a Varian 60 mm dual-tuned 1 H/ 13 C linear volume coil. Anatomical 1 H images were acquired for slice planning and positioning. 13 C intensity maps were generated and displayed as overlays on grayscale 1 H images. In separate experiments, in vivo HP- 13 C-MRS data acquisition was initiated immediately after the pyruvate injection. Results: The HP signals from [1- 13 C]lactate, [1- 13 C]alanine, and 13 C-bicarbonate were detected in real-time 13 C spectra from hearts following injection of HP[1- 13 C]pyruvate. In hearts with partial coronary ligation, the MRS data were acquired from a mixture of ischemic and nonischemic myocardium. A 27% decrease in bicarbonate production was observed in hearts with ischemic myocardium compared to control hearts. After stimulation of NM hearts with dobutamine, less bicarbonate was produced from HP-pyruvate likely due to an increased contribution of other endogenous substrates to acetyl-CoA. Production of bicarbonate was unchanged in IM hearts following adrenergic stimulation. Conclusions: Our results demonstrated that decreased oxidative metabolism of pyruvate as a result of myocardial ischemia and dobutamine stress.
Abstract 12818: Identifying Drivers of Hospital Readmission Through Analysis of Discrepant Predicted and Observed Readmission Status
Authors: Allison Kratka, Jodi Dalto, Jennifer Beloff, Hojjat Salmasian, Kathryn Britton
Journal: Circulation (2020)

Introduction: The Hospital Readmissions Reduction Program (HRRP) lowers Medicare payments to hospitals with excess readmissions for certain conditions. We analyzed FY2020 HRRP data for Brigham and Women’s Hospital (July 2015 to June 2018). We conducted an analysis to identify patients with a discrepant expected vs observed readmission status for AMI, HF and CABG, followed by a chart review to explain this discrepancy. Methods: We calculated the risk of readmission for each patient, which was a summed value of the weights associated with all recorded comorbidities in the CMS data. A negative risk score indicated a patient was unlikely to be readmitted and a positive score indicated the opposite. We then performed a chart review focused on patients who had a high risk of readmission but were not readmitted, and those who had a low risk of readmission but were readmitted. Results: For AMI, 18% (108/596) of patients were readmitted within 30 days, CABG 14% (50/357) of patients, and HF 27% (367/1382) of patients. For AMI, risk of readmission scores ranged from 2.75 to -0.095. 5/596 patients had a negative score, and none were readmitted. For CABG, scores ranged from 2.64 to -0.31, 58/357 people had a negative score, and 6 were readmitted. For HF, scores ranged from 1.94 to 0.055. There were no negative scores, but of the lowest 20/1382 scores, 2 were readmitted. We then performed a chart review of 37 patients whose readmission status was discordant with their risk score, and examined why this occurred. For patients who were low risk but were readmitted across all three conditions, 30% (range 10% - 54%) did not have a follow up appointment scheduled before discharge, 11% (range 0% - 29%) did not have an advanced care plan and 95% (range 86% - 100%) had not had a SIC. Patients who were high risk but not readmitted were evaluated but did not have any notable characteristics. We did not find any evidence of under-coding of risk comorbidities that would have led to falsely low risk scores. Conclusions: Patients with more comorbidities were more likely to get readmitted, and we found these risk factors to be accurately recorded. Clinical care insights from this project include the need for more SICs and palliative care consults and a more targeted effort to ensure patients have appropriate follow-up.
No evidence for a change of the current HbA1c target level of l 6,5%(48 mmol/mol) in children and adolescents with diabetes in Sweden and UK
Authors: Ragnar Hanås, Niels Birkebaek, Annelie Carlsson, Gun Forsander, Anna-Lena Fureman, Lena Hanberger, Anna Olivecrona, Eva Örtqvist, Auste Pundzuite-Lyckå, Frida Sundberg, Stefan Särnblad, Fiona Campell, Karin Åkesson, Ulf Samuelsson
Journal: BMJ (2019)

No evidence for a change of the current HbA1c target level of < 6,5%(48 mmol/mol) in children and adolescents with diabetes in Sweden and UK
Abstract 13124: Exercise Capacity as a Predictor of the Placebo-controlled Efficacy of Percutaneous Coronary Intervention in Stable Coronary Artery Disease: The Ventilatory Gas Exchange-stratified Analysis of ORBITA
Authors: Sashiananthan Ganesananthan, Christopher Rajkumar, Matthew Shun-Shin, Alexandra Nowbar, Michael Foley, Henry Seligman, Roland Wensel, John Davies, Darrel Francis, Rasha K Al-Lamee
Journal: Circulation (2020)

Introduction: Improvement in exercise capacity is a therapeutic goal of percutaneous coronary intervention (PCI) for stable coronary artery disease (CAD). Cardiopulmonary exercise testing (CPET) provides an accurate quantification of cardio-respiratory fitness through analysis of ventilatory gas exchange (VGE). The aim of this secondary analysis from the ORBITA trial is to determine the placebo-controlled effect of PCI on VGE parameters and determine if pre-randomisation exercise capacity predicts the placebo-controlled efficacy of PCI. Methods: Following a 6-week medication optimisation phase, patients with severe single vessel CAD underwent pre-randomisation treadmill CPET using the smoothed modified Bruce protocol. Patients were then randomly assigned to PCI or a placebo procedure. At the end of the 6-week follow up period, patients underwent repeat CPET before being unblinded to treatment allocation. Results: CPET data was available for 195 patients (mean age 66.1 ± 9.1, 73.3% male). At baseline, peak oxygen uptake (VO 2 ) was 21.5±6.7ml/kg/min in the PCI arm (n=102) and 20.6±6.6ml/kg/min in the placebo arm (n=93). At follow up, there was no significant benefit from PCI over a placebo procedure for any ventilatory gas exchange (peak VO 2 , p=0.826; O 2 -pulse plateau, p=0.638) or haemodynamic parameter (rate-pressure product, p=0.215). Although PCI resulted in significantly improved patient-reported freedom from angina (OR, 2.58 [95% CI, 1.35-14.92] p=0.004) and angina frequency score (OR, 1.73 [95% CI, 1.02 to 2.96], p=0.0432), there was no detectable interaction between peak VO 2 and these endpoints (P interaction(int) =0.715 and P int =0.588 respectively). Similarly, pre-randomisation peak VO 2 did not predict the placebo-controlled benefit of PCI on physical limitation (P int =0.293), quality of life (P int =0.380), EuroQOL 5 visual analogue score (P int =0.695), Canadian Cardiovascular Society angina class (P int =0.120) or exercise time (P int =0.897). Conclusions: When assessed against placebo, PCI does not improve VGE or exercise capacity, assessed by CPET. Furthermore, pre-randomisation exercise capacity does not predict the placebo-controlled effect of PCI on symptom relief, even in patients with lower functional capacity.
Abstract 14922: Association of Increase of Serum Albumin Levels During Hospitalization With 1-year Outcomes for Acute Heart Failure
Authors: Takao Kato, Hidenori Yaku, Neiko Ozasa, Erika Yamamoto, YASUTAKA INUZUKA, Yodo Tamaki, Takeshi Kimura
Journal: Circulation (2020)

Introduction: Hypoalbuminemia is a well-known prognostic factor in acute heart failure (AHF). Hypothesis: We hypothesized that there is an favorable association of the increase in serum albumin levels during hospitalization with 1-year clinical outcomes in patients hospitalized for AHF. Methods: Using the data of the consecutive 3717 patients hospitalized for AHF and discharged alive in the Kyoto Congestive Heart Failure registry, we evaluated the baseline and therapeutic factors associated with the increase of serum albumin levels during hospitalization for AHF. Next, we compared the effect of increase of albumin for the primary composite outcome measures compromising all-cause death and HF hospitalization using a Cox proportional hazard model. Results: The patients in the increase of albumin group (N=1083, 34%) were younger and less likely to have a larger body mass index and renal dysfunction than those in the non-increase group (N=2077, 66%). Median follow-up was 470 days with 96% 1-year follow-up rate. The risk for the primary outcome measure in the increase group relative to the non-increase group was significantly low (adjusted hazard ratio [HR]: 0.78, 95% confidence interval [CI]: 0.69-0.90: P=0.0004) after adjusting confounders including baseline albumin levels. When stratified by the quartiles of albumin levels at discharge, the trend was more evident in the lower quartiles of albumin levels but without interaction (interaction P=0.38). Conclusions: The increase of albumin was associated with lower 1-year risk for the composite of all-cause death and HF hospitalization in patients with hospitalized AHF, independently of baseline albumin levels.
Abstract 16056: The Prevalence, Risk Factors and Outcome of Cardiac Dysfunction in Hospitalized Patients With Covid-19
Authors: Mingxing XIE, Yuman Li, He Li, Yuji Xie, Meng Li, Li Zhang
Journal: Circulation (2020)

Objectives: We aimed to investigate the prevalence, risk factors and outcome of cardiac dysfunction, and explore the potential value of echocardiographic parameters in hospitalized patients with coronavirus disease 2019 (COVID-19). Background: Cardiac involvement is a prominent features in COVID-19. However, the prevalence and clinical significance of cardiac dysfunction in COVID-19 patients have not yet been well described. Methods: We studied 157 consecutive hospitalized COVID-19 patients, whose Left ventricular (LV) and right ventricular (RV) structure and function were evaluated by echocardiography. Results: RV dysfunction was found in 40 (25.5%) patients, and LV dysfunction in 28 (17.8%) patients consisting of 24 (15.3%) with heart failure with preserved ejection fraction and 4 (2.5%) with heart failure with reduced ejection fraction. Hypertension, acute respiratory distress syndrome (ARDS), high-sensitivity troponin I (hs-TNI) level and mechanical ventilation therapy was associated with cardiac dysfunction, which contributed to higher mortality (LV dysfunction: 28.6% vs 11.6%, P = 0.022; RV dysfunction: 37.5% vs 6.8%, P &lt; 0.001, respectively). Moreover, LV and RV dysfunction were more frequent in patients with elevated hs-TNI than those without (37.5% vs 12.5 %, P = 0.001; 40.0 % vs 22.9%, P = 0.043, respectively). During hospitalization, 23 patients died. The mortality was 3.0% for patients without cardiac dysfunction and normal hs-TNI levels, 6.7% for those with cardiac dysfunction and normal hs-TNI levels, 13.3% for those without cardiac dysfunction but elevated hs-TNI levels, and 64.0% for those with cardiac dysfunction and elevated hs-TNI. In Cox analysis, RV dysfunction was independently predictor of higher mortality (hazard ratio=2.79; 95% CI: 1.10 to 7.06; P=0.031). HF, especially HFpEF, was not predictive of increased mortality. Conclusions: The prevalence of RV dysfunction was higher than that of HF. Moreover, HFpEF was more common than HFrEF. RV dysfunction is an independent predictor of higher mortality. Additionally, patients with cardiac dysfunction and elevated hs-TNI had the highest mortality, which may prompt physicians to pay attention not only to the hs-TNI level but also the cardiac dysfunction.
Macrophage expression and prognostic significance of the long pentraxin PTX3 in COVID-19
Authors: Enrico Brunetta, Marco Folci, Barbara Bottazzi, Maria De Santis, Giuseppe Gritti, Alessandro Protti, Sarah N. Mapelli, Stefanos Bonovas, Daniele Piovani, Roberto Leone, Ilaria My, Veronica Zanon, Gianmarco Spata, Monica Bacci, Domenico Supino, Silvia Carnevale, Marina Sironi, Sadaf Davoudian, Clelia Peano, Francesco Landi, Fabiano Di Marco, Federico Raimondi, Andrea Gianatti, Claudio Angelini, Alessandro Rambaldi, Cecilia Garlanda, Michele Ciccarelli, Maurizio Cecconi, Alberto Mantovani
Journal: Nature Immunology (2020)
SAT0072 Celecoxib does not affect index joint x-rays in osteoarthritis (oa) patients with long term exposure
Authors: EA Tindall
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Worsening of joint x-rays has been observed with nonsteroidal anti-inflammatory drug (NSAID) use. <h3>Objectives</h3> The effect of celecoxib, a specific cyclooxygenase-2 inhibitor, on index joint (knee or hip) x-rays in patients with OA was determined during a long-term safety trial. <h3>Methods</h3> X-rays were obtained from all patients prior to entry into a controlled clinical trial, prior to subsequent entry into the long-term safety trial, and at Month 12 or early termination visit of the long-term safety trial. Blinded x-rays were graded on a semiquantitative scale assessing multiple aspects of joint morphology. <h3>Results</h3> Overall qualitative interpretation of the individual scores for hip and knee films indicated mild to moderate OA equivalent to an average Kellgren-Lawrence grade of between 2 and 3 at entry to the long-term safety trial. Data from 147 pairs of knee films were analysed prior to and after participation in the long-term safety trial (average duration of treatment, 1 year). Shift table analysis was not significant for any parameters of joint morphology (knee [medial and lateral] joint space narrowing, knee [medial and lateral] spurs, knee [medial and lateral] sclerosis, and knee malalignment). Small mean changes over time were noted for these parameters, but all 95% confidence intervals (CI) overlapped 0. Data from 158 pairs of hip films were analysed prior to and after participation in the long-term safety trial (average duration of treatment, 1 year). Shift table analysis was significant for worsening of hip narrowing (p = 0.029) but not other parameters of joint morphology (hip cysts, hip spurs, and hip sclerosis). Mean change analysis demonstrated a change of 0.14 units/year in hip narrowing (95% CI 0.08–0.20), equivalent to a change of approximately 3% per year. Mean change analysis demonstrated a change of 0.04 units/year in hip cysts (95% CI 0.01–0.08), equivalent to a change of approximately 0.2% per year. These changes were not dose-dependent, and similar changes were noted prior to entry into the long-term safety trial. <h3>Conclusion</h3> Celecoxib did not affect index joint x-rays in OA. Modest changes in hip narrowing noted were consistent with the natural history of the disorder. Sponsored by Pharmacia Corporation and Pfizer, Inc.
Exosome-mediated delivery of kartogenin for chondrogenesis of synovial fluid-derived mesenchymal stem cells and cartilage regeneration
Authors: Xiao Xu, Yujie Liang, Xingfu Li, Kan Ouyang, Manyi Wang, Tong Cao, Wencui Li, Jianquan Liu, Jianyi Xiong, Biquan Li, Jiang Xia, Daping Wang, Li Duan
Journal: Biomaterials (2020)