tbuckley/cabot-search huggingface dataset:
QUALITY OF LIFE AMONG PATIENTS WITH PRIMARY BILIARY CHOLANGITIS DURING CANADA'S STATE OF EMERGENCY RESPONSE TO COVID-19
Authors: S. B. Roberts, B. Aziz, C. Plagiannakos, M. Saini, H. H. Ko, C. Tsien, J. A. Flemming, L. Worobetz, C. Vincent, A. F. Gulamhusein, H. L. A. Janssen, G. M. Hirschfield, A. L. Mason, B. E. Hansen
Journal: Hepatology (2020)

Background: Canadian provinces initiated states of emergency (SoE) between March 13 and March 23 2020 due to community transmission of COVID-19 We explore changes in self-reported quality of life (QoL) in patients with PBC early-on during SoE Methods: Patients with PBC from the Canadian Network for Autoimmune Liver disease who completed QoL questionnaires between July 2019 and June 2020 are included Questionnaires include the Short-Form 36 (SF-36), PBC-40, and Itch Numeric Rating Scale (iNRS) Measurements during SoE are after March 17 2020, date of SoE initiation in Ontario Measurements before Feb 1 2020 are pre-SoE Measurements between Feb 1 and March 16 2020 are excluded given growing societal concern during this time, but no formal SoE Analyses include mixed effects regressions of QoL scores with SoE as a binary variable Models are adjusted for duration of disease and age at diagnosis and employ random intercepts at clinic and patient level Results: 312 patients were included from Toronto (64%, n=198), Montreal (14%, n=43), Edmonton (7 7%, n=24), Ottawa (5 8%, n=18), Saskatoon (5 4%, n=17), and Kingston (3 8%, n=12) The majority of patients were female (93%, n=291), Caucasian (82%, n=256), and born in Canada (78%, n=242) Mean age was 58 6 years (SD 10 8), mean age at diagnosis was 49 3 years (SD 11 0), mean duration of disease was 9 0 years (SD 7 2), and 6 4% (n=20) had overlap with autoimmune hepatitis Patients had a mean of 1 3 (SD 0 5) repeated measures (maximum 3) 219 patients had measures pre-SoE and 128 had measurements during SoE Estimated mean SF-36 physical component scores were similar before and during the first 3 months of SoE (41 9 vs 40 7, p=0 16), as were SF-36 mental component scores (43 3 vs 43 5, p=0 91) When compared to average Canadian population SF-36 scores, patients with PBC had significantly worse scores before and during SoE (p<0 001 all comparisons) PBC-40 domain scores remained stable, with estimated mean values before and during SoE as follows: Symptoms 13 8 vs 14 2 (p=0 32), Fatigue 24 9 vs 25 0 (p=0 81), Cognitive 10 8 vs 11 1 (p=0 47), Socio-Emotional 25 4 vs 26 2 (p=0 20), Itch 4 7 vs 4 9 (p=0 44)  There was a small but statistically significant increase in estimated mean iNRS score, from 2 4 pre-SoE to 3 3 during the first 3 months of SoE (p<0 001)  Conclusion: Quality of life scores remained largely stable during the first three months of Canada's SoE SF-36 scores in patients with PBC were significantly worse than Canada's general population Analyses should be updated as Canada's SoE continues
Abstract 14677: Distribution of 10- and 30-year Predicted Risks for Atherosclerotic Cardiovascular Disease in the United States: NHANES 2015 to 2018
Authors: Nilay S Shah, Hongyan Ning, Amanda Perak, Norrina B Allen, John T Wilkins, Donald M Lloyd-jones, Sadiya S Khan
Journal: Circulation (2020)

Introduction: Premature fatal cardiovascular disease rates have plateaued in the US. Identifying population distributions of short- and long-term predicted risk for atherosclerotic cardiovascular disease (ASCVD) can inform interventions and policy to improve cardiovascular health over the life course. Methods: Among nonpregnant participants age 30-59 years without prevalent CVD from the National Health and Nutrition Examination Surveys 2015-18, continuous 10 year (10Y) and 30 year (30Y) predicted ASCVD risk were assigned using the Pooled Cohort Equations and a 30-year competing risk model, respectively. Intermediate/high 10Y risk was defined as ≥7.5%, and high 30Y risk was chosen a priori as ≥20%, based on 2019 guideline levels for risk stratification. Participants were combined into low 10Y/low 30Y, low 10Y/high 30Y, and intermediate/high 10Y categories. We calculated and compared risk distributions overall and across race-sex, age, body mass index (BMI), and education using chi-square tests. Results: In 1495 NHANES participants age 30-59 years (representing 53,022,413 Americans), median 10Y risk was 2.3% and 30Y risk was 15.5%. Approximately 12% of individuals were already estimated to have intermediate/high 10Y risk. Of those at low 10Y risk, 30% had high 30Y predicted risk. Distributions differed significantly by sex, race, age, BMI, and education (P&lt;0.01, Figure ). Black males more frequently had high 10Y risk compared with other race-sex groups. Older individuals, those with BMI ≥30 kg/m 2 , and with ≤high school education had a higher frequency of low 10Y/high 30Y risk. Conclusions: More than one-third of middle-aged U.S. adults have elevated short- or long-term predicted risk for ASCVD. While the majority of middle-aged US adults are at low 10Y risk, a large proportion among this subgroup are at high 30Y ASCVD risk, indicating a substantial need for enhanced clinical and population level prevention earlier in the life course.
Immune profiling of uveal melanoma identifies a potential signature associated with response to immunotherapy
Authors: Yong Qin, Kathryn Bollin, Mariana Petaccia de Macedo, Fernando Carapeto, Kevin B Kim, Jason Roszik, Khalida M Wani, Alexandre Reuben, Sujan T Reddy, Michelle D Williams, Michael T Tetzlaff, Wei-Lien Wang, Dan S Gombos, Bita Esmaeli, Alexander J Lazar, Patrick Hwu, Sapna P Patel
Journal: Journal for ImmunoTherapy of Cancer (2020)

To date, no systemic therapy, including immunotherapy, exists to improve clinical outcomes in metastatic uveal melanoma (UM) patients. To understand the role of immune infiltrates in the genesis, metastasis, and response to treatment for UM, we systematically characterized immune profiles of UM primary and metastatic tumors, as well as samples from UM patients treated with immunotherapies. Relevant immune markers (CD3, CD8, FoxP3, CD68, PD-1, and PD-L1) were analyzed by immunohistochemistry on 27 primary and 31 metastatic tumors from 47 patients with UM. Immune gene expression profiling was conducted by NanoString analysis on pre-treatment and post-treatment tumors from patients (n=6) receiving immune checkpoint blockade or 4-1BB and OX40 dual costimulation. The immune signature of UM tumors responding to immunotherapy was further characterized by Ingenuity Pathways Analysis and validated in The Cancer Genome Atlas data set. Both primary and metastatic UM tumors showed detectable infiltrating lymphocytes. Compared with primary tumors, treatment-naïve metastatic UM showed significantly higher levels of CD3+, CD8+, FoxP3+ T cells, and CD68+ macrophages. Notably, levels of PD-1+ infiltrates and PD-L1+ tumor cells were low to absent in primary and metastatic UM tumors. No metastatic organ-specific differences were seen in immune infiltrates. Our NanoString analysis revealed significant differences in a set of immune markers between responders and non-responders. A group of genes relevant to the interferon-γ signature was differentially up-expressed in the pre-treatment tumors of responders. Among these genes, suppressor of cytokine signaling 1 was identified as a marker potentially contributing to the response to immunotherapy. A panel of genes that encoded pro-inflammatory cytokines and molecules were expressed significantly higher in pre-treatment tumors of non-responders compared with responders. Our study provides critical insight into immune profiles of UM primary and metastatic tumors, which suggests a baseline tumor immune signature predictive of response and resistance to immunotherapy in UM.
Abstract 14193: Depression Worsens Cardiovascular Health: A Population-based Cohort Study (NHANES, 2015-16)
Authors: Brent Medoff, Andrew Baird, Brandon Herbert, Jared W Magnani
Journal: Circulation (2020)

Introduction: Depression increases cardiovascular risk, but associations between depression and cardiovascular risk profiles have had limited investigation. We hypothesized that depression is associated with cardiovascular risk factors in a population-based cohort. Methods: We selected participants from the 2015-16 National Health and Nutrition Examination Survey (NHANES) and age ≥25 years. Participants completed the Patient Health Questionnaire (PHQ), a 9-item, validated instrument categorizing minimal (0-4), mild (5-9) or moderate-to-severe (≥10) depression. We employed the American Heart Association’s assessment of cardiovascular health, Life’s Simple 7 (LS7) which uses risk factors (smoking status, BMI, physical activity, diet, cholesterol, blood pressure, and glycohemoglobin) to categorize cardiovascular health as poor (0-1), intermediate (5-9) or ideal (10-14). We related PHQ scores to cardiovascular health as measured by LS7 in regression analyses adjusted for relevant covariates (age, sex, race, education, health insurance and poverty-income level). Results: Among 5053 NHANES participants, 4003 (79%) had data for the PHQ and determination of LS7 scores (age 51±16; 52% female; 67% white race). Individuals with mild depression (PHQ 5-9) had 1.4-times greater likelihood (95% CI, 1.07-1.92) of lower cardiovascular health compared to those without depression in multivariable-adjusted models. Likewise, individuals with moderate depression (PHQ≥10) had 3-times greater likelihood (95% CI, 1.90-4.97) of lower cardiovascular health compared to those without depression. Conclusions: In a socially diverse cohort, individuals with depression were more likely to have significantly lower cardiovascular health compared to those without depression. Our findings show that depression may be a barrier to cardiovascular health promotion. Addressing depression appears essential to improve cardiovascular health.
Abstract 16895: Interrelation of Exercise Training, Cardiorespiratory Fitness, and Cardiac Biomarkers in Patients Enrolled in the Health Benefits of Aerobic and Resistance Training in Individuals With Type 2 Diabetes Study
Authors: Amit Saha, Kershaw Patel, Colby Ayers, Jarett D Berry, Neil Johannsen, Christopher DEFILIPPI, Timothy Church, James A De Lemos, Ambarish Pandey
Journal: Circulation (2020)

Introduction: Low cardiorespiratory fitness (CRF) and elevated biomarker levels of myocardial injury and inflammation are both associated with heart failure (HF) risk. While exercise training (ET) is associated with improvement in CRF, the interrelationships among CRF, cardiac biomarkers, and ET are not well established. Methods: Participants of the Health Benefits of Aerobic and Resistance Training in Individuals with Type 2 Diabetes study were included. High-sensitivity cardiac troponin T (hs-cTnT), growth differentiation factor-15 (GDF-15), N-terminal pro-B-type natriuretic peptide (NT-proBNP), and peak oxygen uptake (VO 2peak ) were assessed at baseline and at 9 months on completion of ET. Longitudinal change in cardiac biomarkers across treatment groups (control versus ET) were assessed using paired t-tests. Multivariable-adjusted linear regression was performed to identify factors associated with follow-up cardiac biomarkers and ΔVO 2peak . Results: This study included 166 participants randomized to control (n = 31) and ET groups (n = 135). There was no significant change in hs-cTnT or NT-proBNP from baseline to follow-up among ET and control group participants. GDF-15 increased among participants randomized to the control (P = 0.01) but not the ET group. In adjusted analysis, each ET regimen was independently associated with lower follow-up GDF-15 but not with change in other biomarkers ( Table ). ΔVO 2peak was not associated with any follow-up biomarker level in adjusted analysis. Among individuals in the ET group, baseline hs-cTnT and GDF-15 were each significantly associated with ΔVO 2peak [per 1-unit higher log(hs-cTnT): β= -0.18 (95% CI = -0.31, -0.05); per 1-unit higher log(GDF-15): β = 0.08 (95% CI = 0.01, 0.15)]. Conclusions: Among patients with type 2 diabetes, ET was associated with reduction in GDF-15 but not with change in other biomarkers. Baseline hs-cTnT and GDF-15 were each independent predictors of CRF change in response to ET.
Abstract 14995: Family History of Coronary Artery Disease in Patients With Vasospastic Angina: What Does it Mean Clinically?
Authors: Hiroki Teragawa, Chikage Oshita, Yuichi Orita
Journal: Circulation (2020)

Introduction: It has been reported that a family history of coronary artery disease (FH-CAD) is one of the coronary risk factors for CAD with organic coronary stenosis (o-CAD). Hypothesis: However, the indication for FH-CAD in patients with vasospastic angina (VSA) is yet to be fully elucidated. Therefore, we investigated the frequency of FH-CAD in patients with VSA and examined the clinical characteristics of patients with VSA with FH-CAD. Methods: A total of 78 patients with VSA diagnosed by coronary angiography and spasm provocation test (SPT) were included. Patients with cardiomyopathies, long QT syndrome, or Brugada syndrome, were excluded. On SPT, VSA was defined as &gt;90% narrowing of coronary artery in response to acetylcholine accompanied with chest symptoms and/or ST- T changes on ECG. Each patient was interviewed about their FH-CAD, and its presence was defined as having known CAD and sudden cardiac death affecting first-degree relatives. According to the presence of FH-CAD, patients with VSA were classified into the two groups: Group I, with FH-CAD; and Group II, without FH-CAD. Conventional risk factors, blood chemical parameters, vascular function, including flow-mediated dilation (FMD) and nitroglycerin-induced dilation (NID), duration of angina, were checked. Furthermore, the frequency of FH-CAD was checked in 161 patients with o-CAD (≥50% coronary stenosis) and 69 patients without o-CAD or VSA (non-CAD) . Results: Group I and Group II comprised 17 (21%) and 61 patients (79%), respectively. The frequency of FH-CAD in patients with VSA was not significantly different between o-CAD and non-CAD groups (17% vs. 16%). The conventional coronary risk factors, blood chemical parameters, and FMD (3.2 ± 3.1%, vs. 3.4 ± 3.8%) were not significantly different between Group I and Group II. In contrast, NID and duration of angina were significantly higher in Group I than in Group II, (18.2 ± 9.1% vs. 14.0 ± 5.2%; 52 ± 15 months vs. 16 ± 7 months, respectively; both p &lt; 0.05). Conclusions: These findings suggest that the FH-CAD is associated with the duration of angina and abnormal vascular smooth muscle function. Thus, FH-CAD may provide clinically important information regarding the activity and the possible mechanism, even in patients with VSA.
Antibacterial, pro-angiogenic and pro-osteointegrative zein-bioactive glass/copper based coatings for implantable stainless steel aimed at bone healing
Authors: Laura Ramos Rivera, Andrea Cochis, Sarah Biser, Elena Canciani, Sara Ferraris, Lia Rimondini, Aldo R. Boccaccini
Journal: Bioactive Materials (2020)

Stainless steel implants are suitable candidates for bone replacement due to their cytocompatibility and mechanical resistance, but they suffer from lack of bioactivity and are prone to bacterial infections. Accordingly, to overcome those limitations, in this study we developed by electrophoretic deposition (EPD), an innovative surface coating made of (i) zein, a natural fibroblast-friendly polymer, (ii) bioactive glass, a pro-osteogenic inorganic material and (iii) copper containing bioactive glass, an antibacterial and pro-angiogenic material. FESEM images confirmed that porous, uniform and free of cracks coatings were obtained by EPD; moreover, coatings were resistant to mechanical stress as demonstrated by the tape test, resulting in a 4B classification of adhesion to the substrate. The coatings were cytocompatible as indicated by metabolism evaluation of human fibroblasts, endothelial cells and mature or progenitor osteoblasts cultivated in direct contact with the specimens. They also maintained pro-osteogenic properties towards undifferentiated progenitor cells that expressed osteogenic genes after 15 days of direct cultivation. Copper conferred antibacterial properties as biofilm formation of the joint pathogens Staphylococcus aureus, Staphylococcus epidermidis and Escherichia coli was significantly reduced in comparison with copper-free coatings (p < 0.05). Moreover, this anti-infective activity resulted as targeted towards bacteria while the cells viability was preserved when cells and bacteria were cultivated in the same environment by a co-culture assay. Finally, copper ability to recruit blood vessels and to inhibit bacterial infection was confirmed in vivo where the growth of S. aureus biofilm was inhibited and the formation of new (<50 μm diameter spread) blood vessels was observed.
Abstract 252: Resuscitation in Prehospital Stage: Effectiveness and Influencing Factors
Authors: Anita Abula, Aija Maca, Oskars Kalejs
Journal: Circulation (2020)

Background: Sudden cardiac arrest or sudden cardiac death is one of the leading causes of death all over the world. Of particular importance is out-of-hospital cardiac arrest (OHCA) - an important overworld public health issue. In order to help these people and improve their chances of survival, it is necessary to provide assistance as soon as possible. Bystanders are usually non-medical persons why it is more complicated to implement. The objectives of the study were to research effectiveness and influencing factors of resuscitation in prehospital stage and create suggestions and methodical recommendations as possible. Materials and Methods: A retrospective study was developed, which summarizes and analyzes the electronic call cards (IEK) of the Emergency Medical service of Latvia (EMS) for 2018 and 2019. IEK were selected that identified “successful resuscitation” and “unsuccessful resuscitation” as a complication of diagnosis (classification developed and validated by EMS of Latvia). Results: Overall 2538 resuscitations were performed, of which 27,6% were successful resuscitation. About a quarter (24,2%) of all resuscitations happened in a public place. The increase in the number of successful resuscitations is observed for resuscitation events that happened in public places. In most of cardiac arrest cases, bystanders did not perform CPR (60,3%). Arrival time of EMS in 2018 was 7,52 - 8,44 minutes and in 2019 was 7,75 - 8,23 minutes. The research shows that approximately 23% of cases the first monitored rhythm by EMS were VF/pVT. There is a significant difference in the increase in successful resuscitations if EMS performed defibrillation during the call. Conclusions: The most important influencing factors in the outcome of resuscitation are the patient’s age, the location, the first aid provided by bystanders, the time until the arrival of EMS and the first observed heart rhythm in a patient with cardiac arrest. It is necessary to create a register of AED (automated external defibrillator) devices in Latvia and their locations, to ensure the availability of data to the EMS service and the public.
Rational design and characterisation of a linear cell penetrating peptide for non-viral gene delivery
Authors: Emma M. McErlean, Monika Ziminska, Cian M. McCrudden, John W. McBride, Stephen P. Loughran, Grace Cole, Eoghan J. Mulholland, Vicky Kett, Niamh E. Buckley, Tracy Robson, Nicholas J. Dunne, Helen O. McCarthy
Journal: Journal of Controlled Release (2020)
Abstract 13814: Semaglutide Reduces Mace Consistently Across Baseline Triglyceride Levels in Patients With Type 2 Diabetes: A Post Hoc Analysis of the Sustain 6 and Pioneer 6 Trials
Authors: Subodh Verma, Lawrence A Leiter, Marie M Michelsen, David Orsted, Soren Rasmussen, Deepak L Bhatt
Journal: Circulation (2020)

Introduction: Elevated triglyceride (TG) levels may predict CV events, although this has not been evaluated in large contemporary trials. The effects of glucagon-like peptide-1 receptor agonists on major adverse CV events (MACE) across TG levels are not fully characterized. SUSTAIN 6 (NCT01720446) and PIONEER 6 (NCT02692716) were randomized, CV outcomes trials investigating once-weekly and oral semaglutide vs placebo, respectively, in patients with type 2 diabetes at high CV risk. We performed a post hoc analysis to assess the effect of semaglutide vs placebo on the primary endpoints, MACE (CV death, nonfatal myocardial infarction, or nonfatal stroke), and its components in these two trials pooled, across baseline TG levels. Methods: The risk of first MACE with semaglutide vs placebo was evaluated across three baseline TG groups (≤151, &gt;151-≤205, and &gt;205 mg/dL). The effect of semaglutide vs placebo on MACE was estimated with Cox regression by TG level categorically, and continuously when adjusting for baseline TG and high-density lipoprotein-cholesterol (HDL-C) levels. The impact of statin treatment was also assessed. Results: In total, 6,417 patients had baseline TG measurements: 3,191 (49.7%) ≤151, 1,459 (22.7%) &gt;151-≤205, and 1,767 (27.5%) &gt;205 mg/dL; mean (±SD) TGs were 107.3 (26.0), 176.6 (15.6), and 326.5 (197.1) mg/dL, respectively. Overall, semaglutide reduced TGs vs placebo by 5% in SUSTAIN 6 and 6% in PIONEER 6 (p&lt;0.01). The incidence of MACE with placebo increased across increasing TG levels (Figure) . Semaglutide generally reduced the risk of MACE and its components vs placebo across TG groups. Results were consistent when evaluating TGs as a continuous variable (adjusting for baseline TG and HDL-C levels), and regardless of statin treatment. Conclusions: In this post hoc analysis of SUSTAIN 6 and PIONEER 6, over half of patients had elevated TG levels (&gt;151 mg/dL). Semaglutide consistently reduced the risk of MACE vs placebo across baseline TG levels.