bluuebunny/crossref_metadata_2025 huggingface dataset:
Anticancer and Antimicrobial Activity of Some New 2,3-Dihydro-1,5-benzodiazepine Derivatives
Authors: Odame Felix , Madanhire Tatenda , Tettey Clement , Neglo David , Adzaho Francisca , Sedohia Daniel , Hosten Eric C.
Published: November 2023

A series of 2,3-dihydro-1,5-benzodiazepine derivatives have been synthesized and characterized using IR, NMR, GC-MS, single crystal XRD, and microanalysis. The results of their antibacterial activity against methicillin-resistance Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, Bacillus subtilis, Streptococcus mutans, Pseudomonas aeruginosa, Salmonella typhi, and Streptococcus pyrogens indicated that most of the compounds were bacteriostatic (0.125−4 mg/mL) and also exhibited good biofilm inhibition (0.21−72.69%). The compounds were found to be synergistic when used in combination with other antibiotics. The antiproliferative and cytotoxic effects were also investigated against PC-3 prostate cancer and RAW 264.7 macrophage cell lines, respectively, using the MTT assay. Apart from compounds 6 and 7, a good number of the compounds (1, 2, 3, 4, 5, and 8) were selectively toxic to the prostate cancer cells at 20 µM, whilst sparing the normal cells. Compound 3 demonstrated the highest antiprostate cancer effect by reducing the viability of PC-3 cells to (13.75%), which was followed by compounds 1 (47.72%), 2 (48.18%), 4 (62.61%), 5 (66.70%), and 8 (69.55%).
Uremic Pericarditis with Cardiac Tamponade in a Patient on Hemodialysis
Authors: Javed Nismat , Molina Marcos , Nasr Rabih , Diaz-Fuentes Gilda
Published: November 2023

Uremic pericardial effusion and pericarditis in end-stage kidney disease patients remain one of the causes responsible for high rates of morbidity and occasional mortality. While clinical presentation could be variable, clinicians should have a high index of suspicion for uremic pericarditis especially in patients who miss their dialysis sessions. We present a 77-year-old man with end-stage renal disease on dialysis diagnosed with pericarditis and large pericardial effusion complicated by cardiac tamponade and shock. He underwent urgent pericardiocentesis with clinical improvement. The course of the disease can be complicated by shock with multiorgan failure, particularly the liver. The presentation is relatively acute requiring a high level of suspicion, urgent diagnosis, and management to reduce mortality. As the geriatric population increases with associated comorbid conditions, it would be expected that patients undergoing dialysis would increase. Given the uncommon nature of the disease and how these patients have been managed by multiple specialties and care providers, it is important to consider dialysis-related complications in all patients with end-stage renal disease presenting with dyspnea.
Adequate Oxygenation State Maintained during Electroconvulsive Therapy in Nonobese Patients Using the Oxygen Reserve Index: A Pilot Study
Authors: Kadoi Yuji , Ohta Jo , Sasaki Yumeka , Saito Shigeru
Published: November 2023

Some controversial reports have observed oxygen desaturation (defined as percutaneous oxygen saturation (SpO2) < 90%) during electroconvulsive therapy (ECT). The purpose of this pilot study was to examine oxygenation states in eight patients during ECT. In addition to the usual hemodynamic monitors and pulse oximeter, the oxygen reserve index (ORi) was monitored using a pulse oximeter. Patients received either no preoxygenation or preoxygenation with 100% oxygen via a tight-fitting mask for 1 or 3 min before induction of anesthesia. ORi increased after preoxygenation. ORi differed significantly between 3 min of preoxygenation and the other two methods before restarting mask ventilation. SpO2 was significantly increased with all methods before stopping manual mask ventilation or before restarting manual mask ventilation compared with that before preoxygenation. No oxygen desaturation was observed at any time with any treatment methods. In nonobese patients, the adequate oxygenation state as shown by SpO2 and ORi was maintained during ECT even without preoxygenation.
Julio Bosch Bousquet: su vida, su pensamiento y su aporte a la Contabilidad en Chile
Authors: Caiceo Escudero Jaime , Cerda Morales Arturo , Soto Villarroel Gladys
Published: November 2023

Todas las personas involucradas con la contabilidad en Chile unen los principales textos del área con Bosch y Vargas. En efecto, se trata de don Julio Bosch Bousquet y don Luis Vargas Valdivia; sus obras escritas han sido textos obligatorios de estudio a lo largo de nuestro país en los diferentes niveles del sistema educacional, especialmente liceos comerciales, centros de formación técnica, institutos profesionales y universidades, durante los últimos cincuenta años. Sin embargo, no todos conocen la vida, obra educacional y aporte en la Contraloría General de la República de Julio Bosch, entre otros de sus principales hitos profesionales, como la amistad y el trabajo conjunto con Luis Vargas. En estas páginas se incursiona en sus estudios, su familia, su vida, su semblanza personal, su desempeño laboral, tanto a nivel docente como en los ámbitos gubernamental y privado; sus principales acciones a favor de la Contabilidad en Chile en diversos ámbitos: escolar, universitario y gubernamental; el reconocimiento a su labor y su pensamiento educativo.
FIGURE 5 from PRMT5 Inhibitors Regulate DNA Damage Repair Pathways in Cancer Cells and Improve Response to PARP Inhibition and Chemotherapies
Authors: Carter Jack , Hulse Michael , Sivakumar Monisha , Burtell Jessica , Thodima Venkat , Wang Min , Agarwal Anjana , Vykuntam Komali , Spruance Jacob , Bhagwat Neha , Rager Joseph , Ruggeri Bruce , Scherle Peggy , Ito Koichi
Published: November 2023

PRT543 inhibits growth of PARP inhibitor–resistant ovarian and breast cancer models in vitro and in vivo. Cell proliferation of UWB1.289 parental, BRCA1-overexpressing, and olaparib-resistant cell lines was assessed by cell-titer glo assays following 10 days treatment with olaparib (A) or PRT543 (B; n = 3). C,In vivo mouse CDX of A2780 ovarian cancer cells treated with PRT543, olaparib, or in combination (n = 8 mice/group). D,In vivo mouse ovarian cancer PDX (CTG-1086, BRCA1 deletion) with acquired resistance to olaparib was treated with PRT543 or olaparib (n = 10 mice/group). E,In vivo mouse breast cancer PDX (CTG-089, BRCA1/2 hemizygous deletion) with acquired resistance to olaparib was treated with PRT543 or olaparib (n = 10 mice/group). A–E, Data are represented as mean ± SEM. C–E, Asterisks indicate statistical significance from vehicle (**, P <0.01) using a Dunnett test.
Characteristics of Month-by-Month Blood Pressure Variability in Patients on Hemodialysis
Authors: Amari Yoshifumi , Morimoto Satoshi , Yurugi Takatomi , Oyama Yasuo , Nakajima Fumitaka , Shimizu Satoru , Ichihara Atsuhiro
Published: November 2023

Introduction: Poor prognosis in hemodialysis (HD) patients is due to the increased prevalence of cardiovascular diseases among them. We previously reported that higher visit-by-visit blood pressure variability is associated with increased cardiovascular mortality in HD patients. This present study aimed to investigate the characteristics of month-by-month blood pressure variability (MMBPV) in these patients. Methods: A total of 324 maintenance HD patients, who could be followed up for 60 months, were recruited. We used standard deviation (SD), coefficient of variation (CV), and variation independent of the mean (VIM) in pre- and post-dialysis systolic blood pressure (pre- and post-SD, pre- and post-CV, and pre- and post-VIM) as an index of MMBPV. We investigated (1) the reproducibility of MMBPV, (2) relationship between these values and background factors, and (3) association between these values and mortality. Results: MMBPV (pre- and post-SD, pre- and post-CV, and pre- and post-VIM) showed significant reproducibility (intraclass correlation, 0.483 [p < 0.001], 0.553 [p < 0.001], 0.450 [p < 0.001], 0.518 [p < 0.001], 0.456 [p < 0.001], and 0.522 [p < 0.001], respectively). High pre-VIM was associated with high interdialytic weight gain and poor nutritional status. High post-VIM was associated with glucose intolerance, high interdialytic weight gain, and poor nutritional status and associated with high rate of cardiovascular deaths independent of other factors (hazard ratio: 1.104, 95% confidence interval: 1.011–1.207, p = 0.028). Conclusion: These data suggested that pre- and post-VIM in HD patients are reproducible and associated with various background factors, and especially post-VIM is independently correlated with cardiovascular mortality. Further studies are necessary to confirm the mechanism of increased post-VIM and clarify whether reducing post-VIM can improve the prognosis of HD patients.
German Theatre and Intercultural Cinema: A Study of the Japanese Film Adaptations of Gerhart Hauptmann’s Plays
Authors: Pinar Alex
Published: November 2023

In the 1920s Westernization and modernism characterized the cultural life of big Japanese cities, and the cinema quickly became the main entertainment of the urban masses. In this decade studios began to shoot movies following the cinematic techniques and narrative styles of European and American cinema, and increased production of film adaptations of Western literature works popular at that time. This paper focuses on the adaptations of German literature works, specifically of Gerhart Hauptmann plays, produced in Japan during the 1920s. While those films have been lost, stills and reviews of film magazines published at the time of screening have been archived. The study draws on these materials and examines the intertextual and intercultural relations between the films and the literary works. It provides a brief overview on the reception of German literature in Japan, compares the plays and films analysing the permutations in narratological elements, and offers insights on how cultural, political, and social context influenced the directors’ adaptation process.
A edição histórico-crítica alemã
Authors: Marques Inês
Published: November 2023

O presente artigo aborda o modelo histórico-crítico proposto por Hans Zeller, definindo-se, primeiramente, o conceito de versão. De seguida, explica-se que, neste cenário, todos os testemunhos atestadamente autógrafos possuem o mesmo nível de autoridade dentro da tradição do texto, uma vez que correspondem à vontade do autor em determinados momentos da história do texto. Em contraste com esta posição, retratam-se as ideias subjacentes ao método do copy-text, paradigma editorial anglo-saxônico que defende a valorização da intenção final do autor, sendo apenas as lições que representam a última vontade do autor relativamente ao seu texto aquelas que devem figurar na edição crítica.
Sensualidade e regressão nos romances brasileiros de Robert Menasse
Authors: Krausz Luis
Published: November 2023

Este artigo discute a imagem do Brasil nos romances brasileiros de Robert Menasse Sinnliche Gewißheit e Selige Zeiten, brüchige Welt. Os conceitos de sensualidade e de regressão desempenham um papel central nos enredos desses romances, relacionando-se, particularmente, com os retratos que o autor faz dos brasileiros. O alívio que a mímese e a regressão proporcionam ao indivíduo, como mostra Jeanne-Marie Gagnebin, estão na base de um prazer dionisíaco, que é associado por Menasse aos brasileiros. Esta experiência mimética relaciona-se ao abandono de identidades culturais cristalizadas e à dissolução do “eu” no sonho (ou pesadêlo) coletivo chamado por Hegel de sinnliche Gewissheit. Suas representações no romance podem ser entendidas como críticas ao Brasil à época do fim da ditadura militar.
Mulheres que migram e gestam: a utilização de uma cartilha multilíngue
Authors: Teixeira Stéfani Clara Campos , Tallamini Elsa Cristine Zanette
Published: November 2023

Ao voltarmos o olhar para a feminização da migração, reconhece-se que elas sofrem violações para além do ser mulher, sendo expostas a questões relacionadas ao ser migrante, situação em que há fragilidade da rede de apoio, assim como dificuldades de acesso às políticas públicas devido às barreiras linguísticas e culturais. O objetivo desta pesquisa é analisar a efetividade do uso de uma cartilha multilíngue durante a internação pós-parto. Trata-se de um estudo de caráter qualitativo, exploratório e descritivo, que utiliza a entrevista semiestruturada como instrumento para a coleta de dados. Diante disso, o tema da maternidade atravessa as esferas de reconhecimento das mulheres migrantes como sujeitos e amplia as adversidades relacionadas à gestação e à criação de seus filhos longe de sua família e de sua cultura. Por fim, os resultados evidenciam que a cartilha é um importante instrumento para o cuidado e uma forma de acolher e democratizar informações, além de ser um mecanismo para a aprendizagem.
Plataformas e mediação orquestral: o caso da Filarmônica de Minas Gerais
Authors: Barros José Márcio Pinto de Moura , Marques Pedro Henrique Mendonça , Almeida Tayane Bragança de
Published: November 2023

O consumo de produtos e serviços culturais digitais radicalizou-se durante o isolamento social imposto pela pandemia de covid-19. Neste artigo, desenvolveu-se um estudo de caso de concertos disponibilizados pela Orquestra Filarmônica de Minas Gerais no YouTube a partir de 2020. Os dados coletados foram analisados diante do trabalho de autores como Barros, Honorato, Hennion, Mörsch, Dobson e outros. A partir dessa análise, indicaram-se pontos positivos e passíveis de melhorias nas iniciativas estudadas. Considerou-se, ainda, que o uso de plataformas é promissor no caso da transmissão de concertos, principalmente pela quebra de seus ritos instituídos. No entanto, há uma lacuna a ser preenchida pela criação de estratégias que compreendam melhor tanto as dinâmicas das plataformas quanto da mediação cultural dentro e fora desse espaço.
Abstract 12503: Both Heart Failure With Reduced and Preserved Ejection Fraction Should Be Included in the CHA
2
DS
2
-VASc Score: A Taiwanese Longitudinal Cohort
Authors: Cheng Chien-Chien , Huang Pang-Shuo , Tsai Chia-Ti
Published: November 2023

Background:
Congestive heart failure (CHF) is a known risk factor for atrial fibrillation (AF)-related thromboembolic stroke. The CHA2DS2-VASc score incorporates CHF but was developed when it primarily referred to patients with reduced ejection fraction (HFrEF). CHF now includes preserved ejection fraction (HFpEF) patients. Therefore, the distinction between stroke risk of AF patients with HFpEF and HFrEF is important for improving risk assessment and management strategies for AF patients.

Methods:
In a longitudinal study utilizing the National Taiwan University Hospital Integrated Medical Database (iMED), 8358 patients with atrial fibrillation (AF) were followed from January 2010 to December 2020 (mean follow-up 3.76 years). Among these patients, 4654 (55.7%) had no history of CHF, 2374 (28.4%) had HFpEF, and 1330 (15.9%) had HFrEF. HFpEF was defined as patients with a left ventricular ejection fraction (LVEF) of 55% or higher. The study evaluated the risk of ischemic stroke using Cox models adjusted for all components of the CHA2DS2-VASc score.

Results:
Patients with HFpEF were older, more frequently female, and had a higher prevalence of previous stroke and hypertension. They also had a higher mean CHA2DS2-VASc score (4.08±1.502 vs. 3.83±1.571, p<0.001) and a higher risk of stroke compared to HFrEF patients (30.1% vs 26.3%, p=0.014). After adjusting for other stroke risk factors with CHA2DS2-VASc score components, there was no significant difference in the risk of stroke between the HFpEF and HFrEF groups (p=0.799).

Conclusion:
Both HFpEF and HFrEF were associated with a higher risk of stroke. Thus, the criteria of "CHF" in the CHA2DS2-VASc score should include HFpEF as well.
Abstract 12514: Direct Oral Anticoagulants versus Warfarin for Preventing Thromboembolic Events in Valvular Heart Diseases Associated Atrial Fibrillation: A Systematic Review and Network Meta-Analysis of Randomized Controlled Trials
Authors: Mohamed Taha Amira , Mohamed Ahmed , Abdelglel Mohamed Yasmeen , Hamouda Esraa , ali Fatmaelzahraa yasser , Hamouda Elkasaby Mohamed , Soliman Youssef , Nasir Yusra , Jaiswal Vikash , Elrosasy Amr
Published: November 2023

Introduction:
Atrial fibrillation (AF) and valvular heart disease (VHD) are common comorbidities, increasing the risk of thromboembolic events. While warfarin has been the standard for preventing stroke in AF patients, direct oral anticoagulants (DOACs) have emerged as an effective substitute. However, their safety and efficacy in VHD patients have yet to be established.

Objective:
To compare the effectiveness and safety of different DOAC agents versus warfarin in patients with AF and VHD in a network meta-analysis (NMA).

Methods:
We conducted an online search of databases for eligible studies from inception to April 2023. For dichotomous variables, we calculated the effect size using the risk ratio (RR) and its confidence interval (CI). We conducted frequentist and pairwise meta-analyses using the random-effects model in R-studio software.

Results:
Seven randomized controlled trials with 17533 patients were included in the review. Analysis of 6 studies showed that dabigatran 150 mg (RR 0.59, 95% CI [0.36, 0.98]) was associated with a lower risk of stroke compared to warfarin. Edoxaban 30 mg was associated with a significantly lower risk of major bleeding (RR 0.43, 95 CI [0.23, 0.81]). Compared to warfarin, dabigatran 110 mg (RR 0.29, 95% CI [0.13, 0.68]), edoxaban 30 mg (RR 0.30, 95% CI [0.11, 0.80]), dabigatran 150 mg (RR 0.36, 95% CI [0.17, 0.77]), edoxaban 60 mg (RR 0.37, 95% CI [0.15, 0.93]), and apixaban (RR 0.40, 95% CI [0.27, 0.61]), were associated with a significantly lower risk of intracranial hemorrhage (ICH). All DOACs did not show any difference in terms of all-cause or cardiovascular mortality, except for rivaroxaban

Conclusion:
In patients with AF and VHD, Edoxaban 30 mg is the safest DOAC agent associated with a reduced risk of major bleeding, ICH, and GI trouble. Dabigatran 150 mg is associated with a reduced risk of stroke and ICH but with a higher risk of GI trouble. However, Rivaroxaban is associated with an increased risk of systemic embolism.
Abstract 12515: Effect of Intravenous Iron Therapy in Patients With Heart Failure and Iron Deficiency: A Meta-Analysis of Randomized Controlled Trials
Authors: Jaiswal Vikash , Jaiswal Akash , Agrawal Vibhor , Ang Song Peng , Kalra Kriti , Bisht Himanshi , Tripathi Apoorva , Biswas Monodeep
Published: November 2023

Background:
Iron deficiency is a frequently observed comorbidity in patients with chronic heart failure (HF). Present guidelines strongly advocate for the routine screening of iron deficiency anemia in all HF patients. Numerous randomized controlled trials (RCTs) have examined the efficacy and safety of intravenous iron-carbohydrate complexes as a supplementation approach for patients with HF with reduced ejection fraction (HFrEF). Nevertheless, there exists a necessity to systematically synthesize the evidence derived from these RCTs through a comprehensive meta-analysis.

Methods:
A comprehensive search was conducted in major electronic databases to identify relevant RCTs. Studies published from inception to April 2023 were scrutinized.

Results:
A total of 14 RCTs with 3597 patients were included in the analysis. The pooled analysis demonstrated a significant reduction in the composite outcome of cardiovascular death or hospitalization for worsening HF (OR 0.55, 95% CI= 0.45, 0.67; p < 0.001). Similarly, the composite outcome of all-cause death or cardiovascular hospitalization showed a significant benefit with intravenous iron supplementation (OR 0.42, 95% CI= 0.28, 0.62; p < 0.001). Moreover, the analysis indicated a significant decrease in hospitalizations for HF among patients receiving IV iron (OR 0.49, 95% CI= 0.32, 0.75; p < 0.001). However, no statistically significant difference was observed in all-cause mortality (OR 0.90, 95% CI= 0.74, 1.10; p = 0.31) and cardiovascular mortality (OR 0.85, 95% CI= 0.68, 1.05; p = 0.14) between the two groups.

Conclusion:
The evidence from this meta-analysis underscores the significance of incorporating IV iron therapy in iron-deficient patients with systolic HF as it demonstrates significant improvements in patient outcomes.
Abstract 12519: Biomarker Characterisation of Heart Failure Subtypes: A Population-Based Bioresource Linked Study
Authors: Lang Chim C , Oo Mon M , Gao Chuang , Cole Christian , Hummel Yoran , Guignard-Duff Magalie , Mordi Ify , Jefferson Emily , Hare James , Palmer Colin , Voors Adriaan A , de Boer Rudolf A , Tromp Jasper , Lam Carolyn S
Published: November 2023

Background:
Deep learning (DL)-based interpretation of echocardiographic images can help create pragmatic cohort studies to validate novel biomarkers. In this study, we have characterised biomarkers implicated in heart failure (HF) pathophysiology across the ejection fraction (EF) range in a DL-supported pragmatic cohort study.

Methods:
We used electronic health record data from Tayside, representing 20% of the Scottish population, between 1993 and 2021. Utilising record linkage to DL automated reading of echocardiographic DICOM images, we identified patients with HFrEF or HFpEF and patients without HF. We then linked identified patients to available plasma samples from the Go-SHARE BioBank. We analysed multi-panel biomarkers, such as NT-proBNP, high-sensitivity cardiac troponin-T (hs-cTnT), growth differentiation factor-15 (GDF-15), insulin-like growth factor-binding protein-7 (IGFBP-7), bone morphogenetic protein-10 (BMP-10), Dickkopf WNT Signaling Pathway Inhibitor-3 (DKK-3), fibroblast growth factor-23 (FGF-23), angiopoietin-2 (Ang2), and fatty acid-binding protein-3 (FABP-3), all with electrochemiluminescence immunoassays (Roche Diagnostics, Germany).

Results:
We identified 236 patients with HFpEF, 156 with HFrEF, and 185 patients without HF with available plasma samples from 3680 patient records linked to echocardiographic DICOMs and blood samples. Patients with HFrEF and HFpEF had significantly higher median values of hs-cTnT, GDF-15, NT-proBNP, IGFBP-7, DKK-3, and FGF-23 than controls. The diagnostic accuracy (AUC) of NT-proBNP, hs-cTnT, GDF-15, IGFBP-7, and FABP-3 was >0.8 for identifying patients with HFrEF or HFpEF from controls. DL-algorithm-based interpretation of DICOM images provided further coverage of echocardiographic parameters relevant for diagnosis of HF subtypes. All biomarkers were associated with all-cause mortality and HF-related hospitalisation during a median follow-up of 1089 days.

Conclusions:
In this population-based study, we demonstrated a novel approach utilising a bioresource linked to a DL-supported pragmatic study to explore biomarkers in HF and demonstrated that multiple biomarkers to have diagnostic and prognostic significance for patients with HFrEF and HFpEF.
Abstract 12520: Advancements in the Treatment of Atherosclerosis
Authors: ALI AHSAN
Published: November 2023

Background:
Endotheliotoxic hyperlipidemia provide impaired eNOS derived NO production, excessive free-radicals, adhesive molecule generation, vascular lipid accumulation, atherosclerosis development & progression. NO replacement by NO donors can restore NO deficit. HDLs have anti-atherogenic properties and are carriers of excessive cellular cholesterol via reverse cholesterol transport (RCT) pathway. Lipoprotein enrichment by anionic phosphatidylinositol (PI) increases the negative surface potential of lipoproteins and stimulate RCT. PI stimulates rapid flux and clearance of plasma choles-l by increased hepatic uptake.

Objective:
Regression of atherosclerosis stimulating RCT with experimental combination of NO donor in PI nanocapsules (AlphaX1).

Methods:
30 rabbits fed with 2%cholesterol diet for 6 months After 6 m subdivided in 3 groups. G1-10 without treatment. G2-treated with AlphaX1 for 10 days, G3-treated for 20 days. 5 rabbits-control. Animals sacrificed after 10 and 20 days of treatment. Abdominal aorta, part snap frozen in cryostat-OilRedO staining, part exposed for morphology and electron microscopy.

Results:
Morphology (x100-x27000): G1-numerous vacuoles with neutral lipids and foam cells under endothelium, proliferation of solitary smooth muscle cells containing lipid vacuoles; G2-moderate deposition of lipid vacuoles & foam cells in sub-endothelium, restoration of endothelium. G3-express reduction of lipid vacuoles & foam cells, restoration of elastic fibers, regeneration of endothelium.OilRedO, C 1.4±0.2% G1 38.2±3.6%. G2 7.3±0.8%, G3 2.3±0.6%.

Conclusion:
Data shows evidence that AlphaX1 provide regeneration of endothelial cells, restoration of elastic fibers (probably due to regulation of fibulin5 by PI3K/Akt), anti-inflammatory effect, clearance of foam cells from neutral lipids and regression of atherosclerosis. AlphaX1 provide antiatherogenic properties of NO and PI, probably by reduction in cytokines production, decrease in adhesion molecules expression, monocyte-endothelium adhesion inhibition, increased cholesterol efflux and plasma clearance via hepatic uptake. AlphaX1 could be a potential new therapeutic agent for prophylaxis & treatment of hyperlipidemia and atherosclerosis.
Abstract 12521: Assessment of Women's Cardiovascular Health Awareness in Lombardy Using Population-Based Web-Survey: The "Call for Women" Project
Authors: Castelvecchio Serenella , Mosca Lori , Ramputi Lucia , Baroni Irene , Aggarwal Brooke , Conte Gianluca , Mazzaccaro Daniela , caruso rosario , Asteria Carmela , Cardani Rosanna , Corbetta Sabrina , Dubini Carola , Boveri Sara , Cerri Ambra , Piepoli Massimo F
Published: November 2023

Introduction:
In Italy, despite the improvements in outcomes, cardiovascular disease (CVD) continue to be the leading cause of death in women.

Hypothesis:
The majority of women has no perception of this risk.

Goals:
Raising awareness among women about their main health threat.

Methods:
Women (≥18 years) living in the Lombardy region were invited from September 2022 to February 2023 to fill in a web-survey distributed in the general population through a public, anonymous link.

Results:
Of 2802 women who answered the call, 2217 (94%) completed the survey, including 107(5%) of women not born in Italy. The mean body mass index was 23.5±4.5 kg/m
2
, with 25,8% of responders being overweight. Despite the perception of that weight gain was a serious problem in a high percentage women (42%), 26.4% of them did not perform any physical activity and 38.7% practiced less than the recommended 150 minutes a week. Nearly half (46.8%) checked their blood pressure annually and 38.2% have never had any CV test. Only 35.5% were aware of CVD as the leading cause of death (LCOD) in women and 2.5% indicated stroke as LCOD, while 40.9% still considered cancer as the greatest health threat for women. Awareness was greater with older age and increasing education and lower among unemployed and menopausal women. The main sources of information about health were considered general practitioner (51.6%) and the web (27.0%). Counterintuitively, women not born in Italy mostly use the Internet (40%, p=0.001). Finally, the survey showed that women were aware of seeing public health education campaigns about breast cancer (72.4%) and violence (19.7%) more frequently than of campaigns about CVD prevention(1.3%).

Conclusions:
Only one-third of all women in this pilot study are aware that CVD is their number one killer. Increasing awareness of CVD as the LCOD among women is a priority, requiring collaboration of healthcare practitioners, professional health organizations, as well as dedication of financial resources.
Abstract 12533: Heart Failure Diagnostic Classification Criteria in Hospitalized Patients Are Associated With Increased Mortality Risk: The Atherosclerosis Risk in Communities (ARIC) Study
Authors: Aladesanmi Oludamilola A , Loehr Laura , Rosamond Wayne D , Li Quefeng , Rossi Joseph , Hall Michael E , Chang Patricia
Published: November 2023

Introduction:
Multiple diagnostic HF classification have been used to identify heart failure (HF) events. Whether these classification criteria can be used for estimating prognosis is unknown.

Research Question:
This study compares multiple research-derived HF classification criteria for predicting mortality in the ARIC study cohort with validated hospitalized acute decompensated heart failure (ADHF) events.

Methods:
There were 1,954 ARIC cohort members with hospitalized HF events from 2005-2019, validated as ADHF by ARIC study classification/adjudication. These HF events were also classified as HF present/absent at the time of hospitalization by other HF classification criteria - Framingham, Modified Boston, NHANES, and Gothenburg. Hazard ratios (HRs) for all-cause mortality at 30 days, 1 year, and 5 years were calculated using logistic regression for all included HF classification criteria compared to ARIC, stratified by ejection fraction (EF), and adjusted for demographics and comorbidities.

Results:
For all ADHF events, Framingham, NHANES, and Gothenburg were prognostic for survival, but not modified Boston criteria (Table). ADHF patients who were also classified as HF by Framingham criteria had a 30% or more increased mortality at 30-day, 1-year, and 5-years regardless of EF, compared to those who were not classified as HF by Framingham (p<0.05). Framingham criteria were prognostic for 30-day survival for those with HFrEF, and also for 1-year and 5-year survival for those with HFpEF.

Conclusion:
The presence of HF as defined using different published criteria is associated with elevated risk of all-cause mortality. To our knowledge, this is a novel study comparing multiple research-derived HF classification criteria for clinical prognostication of mortality in ADHF. More studies are needed to assess the utility of these HF classification criteria for prognostication for HF morbidity and rehospitalization and by HF type.
Abstract 12536: Occurrence of New-Onset Atrial Fibrillation in Patients After Left Atrial Appendage Closure
Authors: Chadha Sakshum , Thapi Sahityasri , Maan Abhishek , Kawamura Iwanari , Needelman Brandon , Patel Richa , Ambesh Paurush , Musikantow Daniel , Turagam Mohit , Whang William , Miller Marc , Dukkipati Srinivas , Reddy Vivek Y
Published: November 2023

Introduction:
Left atrial appendage closure (LAAC) has evolved as a non-pharmacological alternative for stroke prevention in patients with Atrial fibrillation (AF). The occurrence of post-operative AF is well described after cardiac and percutaneous procedures. But, there is limited understanding of the possibility of new-onset AF as a result of LAAC.

Aims:
To investigate the incidence of, and factors associated with, AF after LAAC.

Methods:
We conducted a retrospective analysis of 121 patients with i) paroxysmal AF, 2) had undergone LAAC, and 3) had an implantable electronic devices (CIEDs): pacemaker, defibrillator or implantable loop recorder. Patients with persistent AF and those presenting in AF on the day of LAAC were excluded. Data were collected on baseline characteristics, Colchicine use, antiarrhythmic drugs and prior history of AF ablation. Remote transmissions and device interrogations were analyzed to ascertain new-onset AF during the 6 months follow up period after LAAC. Univariate and multivariable analyses were performed to analyze factors associated with the occurrence of AF after LAAC.

Results:
Of the total 121 patients, 39 (32.2%) developed AF during the 6 month follow up period after LAAC. On univariate analysis, a lower CHA2DS2-Vasc score was associated with a lower incidence of AF post LAAC (OR 0.74, 95% CI 0.55-0.98, p = 0.04). On multivariable analysis, including variables of age, gender, CHA2DS2-Vasc score, use of Colchicine and history of AF Ablation, we observed a statistical trend towards the protective effect of prior AF ablation on occurrence of AF after LAAC (adjusted OR 0.32, 95% CI 0.10-1.05, p =0.06). There was also a statistical trend towards the protective effect of Colchicine on occurrence of AF after LAAC (adjusted OR 0.15, 95% CI 0.02-1.29, p =0.08).

Conclusions:
In our study of paroxysmal AF patients undergoing LAAC, who presented in sinus rhythm on the day of the procedure, the incidence of CIED detected post-procedural AF was 32.2%. We observed statistical trends towards protective effects of prior AF Ablation and use of Colchicine during the peri-LAAC period on occurrence of AF after LAAC.
Abstract 12537: Sedentary Behavior is a Stronger Risk Factor Than Diabetes for Incident Peripheral Artery Disease: Data From the Henry Ford Exercise Testing (FIT) Project
Authors: Ehrman Jonathan K , Keteyian Steven J , Aronow Herbert D , Ahsan Syed , Blaha Michael J , Al-Mallah Mouaz H , Brawner Clinton A
Published: November 2023

Introduction:
Age, diabetes (DM) and smoking are risk factors related to developing peripheral artery disease (PAD). Little is known about the strength of the association of sedentary behavior (SB) or fitness relative to traditional risk factors, and the risk of PAD.

Hypothesis:
SB and fitness are independently related to risk of PAD, but their relative contribution is less than DM and smoking.

Methods:
We assessed 41,268 patients (pts) (age= 55±12 yr, 51% male, 64% white) from the Henry Ford Exercise Testing (FIT) who completed a clinically ordered exercise stress test between January 1991 and June 2009. Fitness (metabolic equivalents of task, METs) was estimated from peak treadmill speed and grade. Patients were asked about current exercise habits and coded as sedentary if not performing regular aerobic mode exercise. Patient self-report and medical records were used to determine smoking history and DM. Those with established PAD at the time of testing were excluded. ICD9 codes 440.XX and 443.9 identified first incidence of PAD from test date up to June 2010. Using multivariable Cox regression (Wald
X
2
, α <0.05) we report on the top 5 predictors of time to incident PAD in ALL pts and stratified by race.

Results:
During a median follow-up of 7.1 yr (IQR 4.2-11.1 yr) there were 2,596 (6%) incident diagnoses of PAD. Wald
X
2
values were rank ordered (Table). SB and fitness were independently related to time to incident PAD. SB ranked the 3
rd
strongest variable for both ALL (HR=2.5 [2.2, 2.9]) and WHITE pts (HR=2.5 [2.1, 2.9]). For BLACK pts SB ranked 2
nd
(HR=2.7 [2.1, 3.6]), above DM and smoking. Fitness ranked 5
th
for ALL and BLACK pts, and 6
th
in WHITE pts.

Conclusion:
In ALL pts, and WHITE and BLACK pts separately, SB was strongly associated with time to incident PAD, and explained more of the variation in incident PAD than DM. In BLACK pts SB was also stronger than smoking. Further research is needed to clarify the role of SB as a potential emerging modifiable risk factor for the development of PAD.
Abstract 12557: Vericiguat Use in a Real-World HFrEF Patient Population: Two Years Post-Launch
Authors: Victores Alejandro , Bash Lori D , Ru Boshu , McMullan Ciaran J , Stevenson Andra S , Januzzi James L , Mentz Robert J
Published: November 2023

Background:
Worsening heart failure events (WHFE) affect up to one-third of patients with HFrEF. Vericiguat, the first agent indicated specifically for a WHF population, is a novel soluble guanylate cyclase (sGC) stimulator approved in 2021 to reduce the risk of cardiovascular death and HF hospitalization.

Objective:
To describe baseline characteristics, comorbidities, and comedication among patients on vericiguat therapy during the first two years after FDA approval.

Methods:
We identified adults in the TriNetX Open Claims Database who filled a prescription for vericiguat between 1 Jan 2021 and 24 April 2023. Summary statistics were computed describing patient and treatment patterns including those of other guideline-directed medical therapy (GDMT), stratified by record of achieving 10mg target dose. Categorical variables compared across groups using Pearson Chi-Square tests and continuous variables were compared across groups using non-parametric Kruskal-Wallis tests.

Results:
Among 5527 patients treated with vericiguat, mean age was 68 years, most were men (67%), and insured by Medicare (47%). Just over one third had a record of achieving the 10mg target dose before data cutoff. Other common GDMT used included beta-blockers (71%), ARNi (47%), MRA (38%) and SGLT2i (39%). Although comorbidities were similar between groups, use of these GDMT classes was statistically significantly higher among patients with a record of achieving target dose of vericiguat (P < 0.05). Similar trends were observed among use of GDMT combinations based on record of achieving target dose (P <0.002).

Conclusions:
Patients with a record of achieving vericiguat target dose were significantly more likely to be on other recommended GDMT and on GDMT combinations despite a similar comorbidity burden. Additional analyses are needed to better understand factors associated with patients reaching classes and target doses of GDMT, including vericiguat.
Abstract 12558: Sodium-Glucose Cotransporter-2 Inhibitor Quality Improvement Initiative for Guideline-Directed Medical Therapy in Heart Failure (SQUAD-HF)
Authors: Gupta Kashvi , Gunta Preetham , Spertus John , Sauer Andrew J
Published: November 2023

Introduction:
Despite efforts encouraging SGLT2i prescriptions at discharge for decompensated heart failure (HF), recent data suggest only 1 in 5 patients receive them with a median odds ratio of 2.5 across hospitals. One of the reasons for under prescription of SGLT2i is cost.

Aim:
We implemented a comprehensive quality improvement initiative, focusing on education and care coordination, at 2 hospitals, to reduce financial barriers to initiation of SGLT2i prior to discharge.

Methods:
Interventions were implemented between October 2022 and January 2023. The education component of the intervention included providing residents, fellows, and faculty information regarding the latest HF guidelines, drug profile, and insurance coverage of SGLT2i through multiple modalities like grand rounds, posters, memes, and a dedicated website with links to published research. The care-coordination component of the intervention included similar presentations to pharmacists, social workers, and care coordinators. Best practices including cost checking of SGLT2i earlier during inpatient stay were encouraged throughout the study period. Primary outcome was a change in physician-reported financial barriers to prescription of SGLT2i assessed by a 10-item survey before and after the interventions.

Results:
Pre- and post-intervention surveys were completed by 82 and 56 healthcare providers; 52% were residents, 8% cardiology fellows, 16% internal medicine attendings, 14% cardiology attendings, and 8% cardiology nurse practitioners respectively. Physicians reported an 18.7% reduction in access and affordability barriers to prescribing SGLT2i for patients admitted with HF, from 86.6% to 67.9% (Table 1).

Conclusion:
Through a comprehensive education initiative and improving care coordination tailored to the health systems, SQUAD-HF reduced physician-reported access and affordability barriers to SGLT2i prescription prior to discharge for patients admitted with HF.
Abstract 12562:
DYRK1A/PPARG/EGR1
Pathway Elicits Endothelial Dysfunctions and Predispose to Developing Pulmonary Hypertension in Down Syndrome
Authors: Suginobe Hidehiro , Narita Jun , Ishii Ryo , Udea Kazutoshi , Yoshihara Chika , Wang Renjie , Ueyama Atsuko , Hashimoto Kazuhisa , Hirose Masaki , Ishida Hidekazu
Published: November 2023

Introduction:
Patients with Down syndrome (DS) have a higher prevalence of pulmonary arterial hypertension (PAH). Pulmonary vascular endothelial dysfunction has been recognized to be one of the predisposing factors to develop PAH, but pathophysiology of pulmonary endothelial cells in DS specific PAH is still unknown.

Hypothesis:
Endothelial dysfunctions contribute to developing PAH in DS.

Methods:
Induced pluripotent stem cell-derived vascular endothelial cells (iPSC-ECs) from DS patients were utilized for analyzing cellular and mitochondrial functions. A Cre-loxP mediated isogenic correction line of disomy 21 was established and used as a control.

Results:
DS-iPSC-ECs showed increased apoptosis, reduced angiogenesis, increased mitochondrial reactive oxygen species, and decreased ATP production, which were all consistent with features of endothelial dysfunctions previously reported in other types of PAH. RNA-seq revealed increased expression of
EGR1
in DS-iPSC-ECs, and its inhibition restored cellular and mitochondrial dysfunctions, demonstrated by si
EGR1
and pioglitazone treatment. Moreover, we revealed that increased expression of
DYRK1a
, one of the major pathogenic genes in DS critical region on chromosome 21, led to elevated
EGR1
expression thorough
PPARG
suppression. These experimental results were reinforced by the observations that pulmonary ECs of a DS patient with severe PAH also exhibited increased EGR1.

Conclusions:
DYRK1A/PPARG/EGR1 pathway in DS is responsible for endothelial dysfunctions and might be a new therapeutic target for DS specific PAH.
Abstract 12564: Safety, Pharmacokinetics, and Lipid Lowering Effects of the Oral, Liver-Targeted Liver X Receptor (LXR) Inverse Agonist TLC-2716 in Healthy Volunteers
Authors: Gane Edward J , Huss Ryan S , Sur Jane , Weng Steve , Murakami Eisuke , Vijayakumar Archana , Kirby Brian J , Subramanian G. Mani , Myers Robert P
Published: November 2023

Background:
The liver X receptors are oxysterol-activated nuclear hormone receptors that regulate cholesterol homeostasis and
de novo
lipogenesis. TLC-2716 is an oral, liver-targeted inverse agonist of LXRα/β in development for severe hypertriglyceridemia (SHTG) and NASH.

Methods:
In this randomized, double-blind, placebo (PBO)-controlled Phase 1 study (NCT05483998), healthy subjects (n=8/2 TLC-2716 vs PBO/cohort) received single ascending doses (SAD) of TLC-2716 (0.5, 2, 6, 12, or 20 mg) or multiple ascending doses (MAD) QD for 14 days (0.5, 2, 6, or 12 mg) while fed or 6 mg fasted. Safety, PK, serum lipid parameters by NMR LipoProfile
®
, and gene expression in PBMCs were evaluated.

Results:
The proportion of subjects with adverse events (AEs) was 60% with PBO and 13-50% with TLC-2716 in the SAD cohorts (n=50), and 40% and 13-88%, respectively, in the MAD cohorts (n=50). All AEs were mild except an unrelated, Grade 2 thrombophlebitis in a subject on TLC-2716 2 mg. TLC-2716 was rapidly absorbed (T
max
2-4h) with a short steady-state half-life (T
1/2
~1.5-2.5h) and low maximal plasma concentrations (C
max
<7 ng/mL), consistent with rapid hepatic uptake. With fed dosing, TLC-2716 AUC and C
max
increased less than dose proportionally and were 25-50% lower on Day 14 vs Day 1. With fasted dosing, exposures were similar on Days 1 and 14 and ~3-fold higher than with fed dosing. Significant, dose-dependent reductions in serum triglycerides, total and LDL-C, total and small LDL particles, and TG/HDL-C ratio—but not HDL-C—were observed with TLC-2716 (
Figure
). Lipid reductions were greatest in subjects with higher baseline values. TLC-2716 did not impact LXR target gene expression (e.g., reverse cholesterol transporters
ABCA1
,
ABCG1
) in PBMCs, supporting its liver-targeted profile.

Conclusion:
The liver-targeted LXR inverse agonist TLC-2716 was well tolerated and caused significant lipid lowering in healthy subjects, supporting its evaluation in patients with SHTG and NASH.
Abstract 12571: Factors That Predict Longitudinal Transition of Symptom Cluster Profiles in Heart Failure
Authors: Wang Zequan , Redeker Nancy S , Walsh Stephen , Tocchi Christine , Kim Kyounghae , Chyun Deborah A
Published: November 2023

Background:
Symptom trajectories in people with heart failure (HF) can vary over time. Few studies have explored how symptom clusters transition, essential to determine interventions.

Aims:
(1) Describe transitions in symptom cluster profiles in people with HF over 8 years; (2) Identify factors predicting the transitions.

Methods:
We conducted secondary analysis of data from the 2008, 2012, and 2016 surveys of the Health and Retirement Study (HRS), using latent transition analysis to identify cluster profiles (fatigue, dyspnea, pain, swelling, depressive symptoms, dizziness), and multinomial regression to determine the predictive factors.

Results:
HRS included 690 HF subjects (57% female; mean age=74.9 (SD =10.04) years). Four cluster profiles were identified: high burden, low burden, distressing, and respiratory-depressive distress. The probability staying in the same profile ranged from 0.60 to 0.89. Male sex (OR=1.39; 95% CI=0.92, 1.82), black race (OR=1.92; 95% CI=1.37, 2.73), smoking (OR=2.44; 95% CI=1.56, 3.71), having diabetes (OR=3.99; 95% CI=2.90, 6.27) and lung disease (OR=1.40; 95% CI=0.83, 1.68) were associated with an increased odds of moving from the distressing to the high burden profile. Smoking (OR=1.17; 95% CI=0.66, 1.55), having arthritis (OR=4.44; 95% CI=2.80, 6.33), lung disease (OR=1.72; 95% CI=1.17, 2.49), and diabetes (OR=3.84; 95% CI=2.87, 5.94) were associated with an increased odds of moving from the respiratory-depressive distress to the high burden profile. Black race (OR=3.58; 95% CI=2.80, 6.20), smoking (OR=1.44; 95% CI=0.91, 2.10), having arthritis (OR=1.71; 95% CI= 1.20, 2.59), lung disease (OR=1.30; 95% CI= 0.55, 1.95), and diabetes (OR=1.81; 95% CI=1.34, 2.90) were associated with an increased odds of moving from the low burden to the distressing profile. Male sex (OR=2.13; 95% CI= 1.66, 3.68), having arthritis (OR=1.51; 95% CI=1.15, 2.13) and lung disease (OR=2.28; 95% CI=1.57, 4.34) were associated with an increased odds of moving from the low burden to the respiratory-depressive distress profile.

Conclusions:
Although symptom cluster profiles remained stable, transitions were observed, and deterioration can occur. The identified predictive factors may enhance long-term symptom management.
Abstract 12573: Differences in Blood Product Consumption Between Ventricular Assist Device and Extracorporeal Membrane Oxygenation During Postoperative Period
Authors: Benjanuwattra Juthipong , Liao Rachel , Nair Nandini
Published: November 2023

Introduction:
Mechanical circulatory supports such as veno-arterial extracorporeal membrane oxygenation (ECMO) and left ventricular assist device (LVAD) are used in advanced heart failure patients. Due to their thrombogenic surfaces, these devices can lead to disseminated thrombosis. The need for anticoagulation also predisposes to hemorrhage, in addition to hemolysis from shear stress. As a result, transfusion of blood components is usually warranted following implantation.

Hypothesis:
To evaluate the differences in the need for transfusion of blood products between these devices during immediate postoperative period up to day 3.

Methods:
Fifty-four patients with advanced heart failure patients admitted at our facility between January 2016-2019 were included. All patients were anticoagulated with continuous heparin infusion. We analyzed the need for packed red blood cells (pRBC), fresh frozen plasma (FFP), and platelet transfusion. Lactate dehydrogenase (LDH), CBC, aPTT, and PT were also measured. The study was approved by Institutional Review Board (#L19-093).

Results:
A total of 54 patients (25 patients received ECMO and 29 patients received LVAD) were included. The median age was 56 years [47-62]. Thirty-eight patients (70.4%) were male. The means daily substitution of pRBC were significantly lower in the LVAD group on day 2 (0.35 vs 2.64 units/day, p=0.002) and day 3 (0.58 vs 1.64 units/day, p=0.028). The means daily substitution of platelets were comparable between the ECMO and LVAD groups. A trend toward the lower mean daily substitution of FFP in the LVAD group on day 2 (0 vs 0.44 units/day, p=0.069) was seen. There was a significantly lower serum LDH in the LVAD group on day 3 (391 ± 345 vs 599 ± 268, p=0.003).

Conclusions:
Data from this retrospective study showed that, compared to ECMO, LVAD was associated with lower rates of hemolysis and pRBC transfusion.