bluuebunny/crossref_metadata_2025 huggingface dataset:
Noninvasive Techniques for Management of Erythema Multiforme
Authors: Martins Fabiana , Pallos Debora , Candeia Jodkandlys , Zerbinati Rodrigo , Braz-Silva Paulo Henrique , Campos Luana
Published: December 2023

An 18-year-old man was referred for a diagnosis of extensive oral lesions. During the interview, he reported a medical history of ganglionic tuberculosis, type 2 herpes infection, and significant weight loss due to dysphagia. Intraoral exam revealed multiple painful and ulcerated lesions covered by pseudomembrane. Lesions were observed on the labial and buccal mucosa, tongue, and soft palate. The laboratory findings included serum positivity for the Epstein-Barr virus, and salivary tests showed positive values for herpes simplex virus (HSV-2) and human herpesvirus (HHV-7). The diagnostic hypothesis was based on clinical findings and viral infection detected in the saliva, which triggered an immunological disorder, that is, erythema multiforme (EM). The treatment consisted of antimicrobial photodynamic therapy (aPDT), with substantial improvement in pain and healing as seen in the following twenty-four hours. Complete resolution of the lesions was achieved five days after the first session. Once the diagnosis of virus-induced EM was confirmed, noninvasive techniques (e.g., salivary tests and aPDT) were very successful and can be indicated for managing these lesions.
Fall Prevention Education Co-Designed and Evaluated with Community-Dwelling Older People Living with Dementia and Their Caregivers: A Feasibility Study
Authors: Francis-Coad Jacqueline , Weselman Tammy , Burton Elissa , Beilby Janet , Hill Anne-Marie
Published: December 2023

Community-dwelling older people living with dementia are at increased risk of falls and injury that may impact their ability to remain at home. Fall prevention education programs have been effective in reducing falling risks in other older populations, but few studies have reported on programs specifically co-designed with this vulnerable cohort. This study partnered with community-dwelling older people living with dementia and their caregivers to co-design a fall prevention education program and evaluate its feasibility. A two-phase, mixed methods design using a community-based participatory research approach was conducted. A co-designed multimedia suite of 16 evidence-based safety messages (screened video, paper brochures), delivered by staff with support from caregivers, was evaluated using pre-and postprogram consumer engagement panels (clients, n = 4 and staff, n = 4), pre-and post-program client and caregiver (n = 18) surveys, and semi-structured educator staff interviews (n = 2). Quantitative data were analysed using Wilcoxon signed-rank tests and qualitative findings were subjected to deductive content analysis and were mapped to known feasibility criteria. Safety messages were positively received, card format delivery was preferred to video, and use of rhymes were fun and engaging. Following the program, older people felt they had a significantly clearer plan to help them prevent falling (

p

 = 0.01). Caregivers who were invested in the program facilitated successful implementation and perceived that the program reduced their concerns about the person they cared for falling. Making the program available at an earlier stage (closer to diagnosis) was deemed preferable for a greater impact. Staff time for engagement and caregivers feeling uncomfortable with technology were two identified threats to implementation. Co-designing and evaluating a fall prevention education program with older people living with dementia, their caregivers, and staff were feasible. Safety messages clarified older peoples’ awareness of how to prevent falls and alleviated caregiver concerns. Education on falling may assist older people living with dementia to remain safe at home.
TABLE 3 from Combination of Itacitinib or Parsaclisib with Pembrolizumab in Patients with Advanced Solid Tumors: A Phase I Study
Authors: Munster Pamela , Iannotti Nicholas , Cho Daniel C. , Kirkwood John M. , Villaruz Liza C. , Gibney Geoffrey T. , Hodi F. Stephen , Mettu Niharika B. , Jones Mark , Bowman Jill , Smith Michael , Lakshminarayanan Mani , O'Day Steven
Published: December 2023

Tumor response by RECIST (full analysis set)
TABLE 2 from Combination of Itacitinib or Parsaclisib with Pembrolizumab in Patients with Advanced Solid Tumors: A Phase I Study
Authors: Munster Pamela , Iannotti Nicholas , Cho Daniel C. , Kirkwood John M. , Villaruz Liza C. , Gibney Geoffrey T. , Hodi F. Stephen , Mettu Niharika B. , Jones Mark , Bowman Jill , Smith Michael , Lakshminarayanan Mani , O'Day Steven
Published: December 2023

Summary of itacitinib and parsaclisib treatment-related TEAEs by MedDRA preferred term (≥5% of patients in the safety population)
TABLE 1 from Combination of Itacitinib or Parsaclisib with Pembrolizumab in Patients with Advanced Solid Tumors: A Phase I Study
Authors: Munster Pamela , Iannotti Nicholas , Cho Daniel C. , Kirkwood John M. , Villaruz Liza C. , Gibney Geoffrey T. , Hodi F. Stephen , Mettu Niharika B. , Jones Mark , Bowman Jill , Smith Michael , Lakshminarayanan Mani , O'Day Steven
Published: December 2023

Summary of demographic and baseline characteristics
Supplementary Table 3 from Combination of Itacitinib or Parsaclisib with Pembrolizumab in Patients with Advanced Solid Tumors: A Phase I Study
Authors: Munster Pamela , Iannotti Nicholas , Cho Daniel C. , Kirkwood John M. , Villaruz Liza C. , Gibney Geoffrey T. , Hodi F. Stephen , Mettu Niharika B. , Jones Mark , Bowman Jill , Smith Michael , Lakshminarayanan Mani , O'Day Steven
Published: December 2023

Supplementary Table 3. Summary of patient disposition (Part 1b Expansion Group A-1/A-2) (Full Analysis Set)
Supplementary Table 10 from Combination of Itacitinib or Parsaclisib with Pembrolizumab in Patients with Advanced Solid Tumors: A Phase I Study
Authors: Munster Pamela , Iannotti Nicholas , Cho Daniel C. , Kirkwood John M. , Villaruz Liza C. , Gibney Geoffrey T. , Hodi F. Stephen , Mettu Niharika B. , Jones Mark , Bowman Jill , Smith Michael , Lakshminarayanan Mani , O'Day Steven
Published: December 2023

Supplementary Table 10. Plasma proteins differentially expressed between cycle 1 day 1 and cycle 2 day 1 with (A) itacitinib plus pembrolizumab (Part 1b Group A-1), or (B) parsaclisib plus pembrolizumab treatment (Part 1b Group B-1/B-2, and Part 2).
Supplementary Table 1 from Combination of Itacitinib or Parsaclisib with Pembrolizumab in Patients with Advanced Solid Tumors: A Phase I Study
Authors: Munster Pamela , Iannotti Nicholas , Cho Daniel C. , Kirkwood John M. , Villaruz Liza C. , Gibney Geoffrey T. , Hodi F. Stephen , Mettu Niharika B. , Jones Mark , Bowman Jill , Smith Michael , Lakshminarayanan Mani , O'Day Steven
Published: December 2023

Supplementary Table 1. Summary of patient disposition (Part 1a Group A) (Full Analysis Set)
FIGURE 2 from Combination of Itacitinib or Parsaclisib with Pembrolizumab in Patients with Advanced Solid Tumors: A Phase I Study
Authors: Munster Pamela , Iannotti Nicholas , Cho Daniel C. , Kirkwood John M. , Villaruz Liza C. , Gibney Geoffrey T. , Hodi F. Stephen , Mettu Niharika B. , Jones Mark , Bowman Jill , Smith Michael , Lakshminarayanan Mani , O'Day Steven
Published: December 2023

IHC analysis of paired screening and on-treatment (week 5–6) tumor biopsies, from patients receiving itacitinib or parsaclisib in combination with pembrolizumab. A, Study Part 1 (T-cell infiltration in combined tumor plus intratumoral stromal regions: CD3+, CD8+, FoxP3+ cells/mm2): itacitinib (Group A-1 and A-2, 300 mg once daily) plus pembrolizumab 200 mg every 3 weeks (upper, n = 9); parsaclisib (Group B, 0.3–1 mg once daily, or 2.5 mg every other day; B-1 and B-2, 20–30 mg once daily) plus pembrolizumab 200 mg every 3 weeks (lower, n = 11). B, Study Part 1 (CD8+:FoxP3+ ratio in combined tumor plus intratumoral stromal regions): itacitinib (300 mg) plus pembrolizumab (left, n = 9); parsaclisib (Group B, 0.3–1 mg once daily, or 2.5 mg every other day; B-1 and B-2, 20–30 mg once daily) plus pembrolizumab 200 mg every 3 weeks (right, n = 11). C, Study Part 2 (T-cell infiltration: CD3+, CD8+, FoxP3+ cells/mm2): parsaclisib 0.3 mg once daily plus pembrolizumab (n = 8 pairs; NSCLC = 1, SCLC = 4, UC = 3). D, Study Part 2 (CD8+:FoxP3+ ratio): parsaclisib 0.3 mg once daily plus pembrolizumab 200 mg every 3 weeks (n = 8 pairs; NSCLC = 1, SCLC = 4, UC = 3). NSCLC, non–small cell lung cancer; SCLC, small cell lung cancer; UC, urothelial carcinoma.
Data from Combination of Itacitinib or Parsaclisib with Pembrolizumab in Patients with Advanced Solid Tumors: A Phase I Study
Authors: Munster Pamela , Iannotti Nicholas , Cho Daniel C. , Kirkwood John M. , Villaruz Liza C. , Gibney Geoffrey T. , Hodi F. Stephen , Mettu Niharika B. , Jones Mark , Bowman Jill , Smith Michael , Lakshminarayanan Mani , O'Day Steven
Published: December 2023

AbstractPurpose:
This phase Ib open-label, multicenter, platform study (NCT02646748) explored safety, tolerability, and preliminary activity of itacitinib (Janus kinase 1 inhibitor) or parsaclisib (phosphatidylinositol 3-kinase δ inhibitor) in combination with pembrolizumab [programmed death-1 (PD-1) inhibitor].
Experimental Design:
Patients with advanced or metastatic solid tumors with disease progression following all available therapies were enrolled and received itacitinib (Part 1 initially 300 mg once daily) or parsaclisib (Part 1 initially 10 mg once daily; Part 2 all patients 0.3 mg once daily) plus pembrolizumab (200 mg every 3 weeks).
Results:
A total of 159 patients were enrolled in the study and treated with itacitinib (Part 1, n = 49) or parsaclisib (Part 1, n = 83; Part 2, n = 27) plus pembrolizumab. The maximum tolerated/pharmacologically active doses were itacitinib 300 mg once daily and parsaclisib 30 mg once daily. Most common itacitinib treatment-related adverse events (TRAE) were fatigue, nausea, and anemia. Most common parsaclisib TRAEs were fatigue, nausea, diarrhea, and pyrexia in Part 1, and fatigue, maculopapular rash, diarrhea, nausea, and pruritus in Part 2. In patients receiving itacitinib plus pembrolizumab, four (8.2%) achieved a partial response (PR) in Part 1. Among patients receiving parsaclisib plus pembrolizumab, 5 (6.0%) achieved a complete response and 9 (10.8%) a PR in Part 1; 5 of 27 (18.5%) patients in Part 2 achieved a PR.
Conclusions:
Although combination of itacitinib or parsaclisib with pembrolizumab showed modest clinical activity in this study, the overall response rates observed did not support continued development in patients with solid tumors.
Significance:
PD-1 blockade combined with targeted therapies have demonstrated encouraging preclinical activity. In this phase I study, patients with advanced solid tumors treated with pembrolizumab (PD-1 inhibitor) and either itacitinib (JAK1 inhibitor) or parsaclisib (PI3Kδ inhibitor) experienced limited clinical activity beyond that expected with checkpoint inhibition alone and showed little effect on T-cell infiltration in the tumor. These results do not support continued development of these combinations.
Emerging Role of Circular RNAs in the Pathogenesis of Retinoblastoma
Authors: Wu Weizhen , Zhang Youjing , Yang Ming
Published: December 2023

Retinoblastoma (Rb) accounts for 3% of all childhood cancers. It is the most common intraocular malignant tumor with a highly aggressive and metastatic phenotype. Gaining a more comprehensive understanding of the molecular mechanisms underlying the proliferation, metastasis, migration, invasive apoptosis, and autophagy processes associated with this cancer would facilitate the design of therapeutic modalities and the identification of novel tumor markers. Recent investigations have shown the contribution of circular RNAs (circRNAs) in the evolution of Rb. Several circRNAs, including circ_0000034, circ_0000527, circ_0075804, circ_0099198, circFAM158A, and circVAPA, promote the progression and metastasis of Rb. However, some circRNAs, such as circ_0001649, circMKLN1, and circTET1, play a tumor suppressive role. In this regard, circRNAs can regulate cancer-developing processes including cell proliferation, apoptosis, migration, invasion, and tumor growth. This review summarizes the functional roles of circRNAs in Rb and their potential clinical applications for diagnosis and prognosis, and provides a comprehensive understanding of the role of circRNAs in the pathophysiology of Rb.
ЗНАЧЕННЯ ПОКАЗНИКІВ КЛІНІЧНОГО АНАЛІЗУ КРОВІ ДЛЯ ВИЗНАЧЕННЯ СТУПЕНЯ ФІБРОЗНОГО ПРОЦЕСУ У ХВОРИХ НА ХРОНІЧНИЙ ГЕПАТИТ С
Authors: Шейко А. Г.
Published: December 2023

Розповсюдження гепатиту С (ГС) називають «тихою епідемією». Хронізація ГС провокує прогресування до фіброзу печінки (ФП) і цирозу печінки (ЦП) й розвитку печінкової недостатності. Перебіг хронічного ГС (ХГС) досить часто має тривалий проміжок «безсимптомності». Тому своєчасне виявлення безсимптомних форм ХГС, які обтяжуються розвитком фіброзного процесу печінки, є однією з актуальних проблем світової медицини. Мета – визначити можливості показників клінічного аналізу крові хворих на ХГС для прогнозування пізніх стадій захворювання (із значним фіброзним процесом). Пацієнти і методи. Здійснено рандомізоване одноцентрове проспективне дослідження випадок-контроль згідно з існуючими етичними нормами з дотриманням принципів Гельсінкської декларації. Обстежено 47 осіб – 28 (59,6 %) чоловіків і 19 (40,4 %) жінок із ХГС і ФП. Розраховано медіану Me та 25,0 % (LQ) і 75,0 % (UQ) квартилі й відносні значення для кількісних та якісних показників відповідно. Показники клінічного аналізу крові визначали загальноприйнятими методами: рівні еритроцитів, гемоглобіну, гематокриту, еритроцитарних індексів (середнього об’єму еритроцита, середнього вмісту гемоглобіну в окремому еритроциті і середньої концентрації гемоглобіну в еритроцитарній масі), тромбоцитів, тромбокриту, кольорового показника, швидкості осідання еритроцитів, лейкоцитів, нейтрофілів (паличкоядерних і сегментоядерних), еозинофілів, лімфоцитів і моноцитів. Результати. Отримані дані свідчать про вірогідні (р=0,025) переважання в 1,08 разу рівнів MCH при 3–4 стадіях ФП (32,8 [29,7; 34,2] пг) порівняно з 0–2 (30,3 [29,5; 31,2] пг). Констатовано вірогідне (р=0,012) перевищення числа тромбоцитів (в 1,28 разу) при 0–2 стадіях ФП (229,0 [185,0; 259,0]×Г/л) порівняно з 3–4 (178,5 [154,8; 204,8]×Г/л). Висновки. Отримані результати зміни показників клінічного аналізу крові хворих на ХГС залежно від перебігу фіброзного процесу печінки можуть бути використані як неінвазивниі прогностичні біомаркери для прогнозування пізніх стадій ХГС (із значним фіброзним процесом).
Reciclagem e tratamento
Authors:   Universidade de São Paulo. Escola de Engenharia de São Carlos, Andrade Julia Fonseca Colombo , Nunes Cleyse Kelly Barbosa ,   Universidade de São Paulo. Escola de Engenharia de São Carlos, Benites Igor Matheus ,   Universidade de São Paulo. Escola de Engenharia de São Carlos, Castro Ana Maria Rodrigues Costa de ,   Universidade de São Paulo. Escola de Engenharia de São Carlos, Schalch Valdir
Published: December 2023

Com o objetivo de celebrar o vigésimo aniversário do Núcleo de Estudo e Pesquisa em Resíduos Sólidos (NEPER) vinculado ao Programa de Pós-Graduação em Engenharia Hidráulica e Saneamento, da Escola de Engenharia de São Carlos, Universidade de São Paulo, em 2023 e promover a disseminação do conhecimento científico na área de resíduos sólidos, foi elaborada esta compilação de obras abrangendo todos os estudos realizados pelo grupo até 2022. O volume 3, intitulado "Reciclagem e tratamento" reune estudos sobre processos tecnológicos de reciclagem; compostagem; digestão anaeróbia; tratamento de resíduos; recuperação energética, integrando as Contribuições cientificas em resíduos sólidos: compilação de estudos do NEPER.
500 exercícios resolvidos de Astrofísica
Authors:   Universidade de São Paulo. Instituto de Astronomia, Geofísica e Ciências Atmosféricas, Maciel Walter Junqueira
Published: December 2023

O livro apresenta uma compilação de exercícios resolvidos de Astrofísica, compreendendo as áreas de Astrofísica Estelar, Ventos Estelares, Astrofísica Galáctica, Meio Interestelar e Evolução Química
Transporte de energia em Astrofísica
Authors:   Universidade de São Paulo. Instituto de Astronomia, Geofísica e Ciências Atmosféricas, Maciel Walter Junqueira
Published: December 2023

O livro examina diversos processos de transporte de energia em Astrofísica, como a radiação, convecção e condução eletrônica, bem como outros processos em que energia é transportada de um objeto a outro. Os principais tópicos discutidos incluem atmosferas e interiores estelares, o meio interestelar e processos dinâmicos em galáxias.
O Fascínio do universo
Authors:   Universidade de São Paulo. Instituto de Astronomia, Geofísica e Ciências Atmosféricas, Damineli Augusto , Steiner João
Published: December 2023

O livro foi editado pelo Prof. Dr. Augusto Damineli e pelo Prof. Dr. João Steiner como parte das comemorações do Ano Internacional da Astronomia (2009). Edições impressas de “Fascínio do Universo” foram distribuídas gratuitamente em escolas, e a edição digital pode ser copiada neste site. Este livro tem como objetivo descrever em linguagem simples, mas com detalhes, o que se sabe sobre alguns aspectos do Universo e como eles são estudados no Brasil. Além dos fatos científicos, ele visa também a destacar o papel cultural e econômico da Astronomia, como inspiração para o desenvolvimento de muitos outros campos da ciência, especialmente dentro da Física e da Matemática. Mais amplamente, a Astronomia forneceu e continua a fornecer ferramentas conceituais decisivas para a astronáutica, para a análise da luz, para a compreensão da energia nuclear, para a procura de partículas atômicas e, em termos do desenvolvimento de materiais e tecnologias, ela manteve-se na fronteira da óptica, da mecânica de precisão e da automação. E, acima de tudo, teve e tem profundo impacto no conhecimento, e é uma das mais refinadas expressões da inteligência humana.
Uma retrospectiva de 50 anos da Astronomia Observacional no Brasil (1952– 2002)
Authors:   Universidade de São Paulo. Instituto de Astronomia, Geofísica e Ciências Atmosféricas, Santos Paulo Marques dos
Published: December 2023

Esta obra registra uma importante memória do “renascer da Astronomia Observacional no Brasil” ocorrido na segunda metade do século passado, e do qual o autor Paulo Marques dos Santos participou pessoalmente como astrônomo e meteorologista. Edição impressa limitada distribuída pelo IAG a cientistas e bibliotecas institucionais.
Abstract 11663: T Wave Alternans: A Clue in Plain Sight
Authors: Gabr Mohamed , Mangeshkar Shaunak , Cerna Luis , Rahgozar Kusha , Al-Taei Mustafa H , grushko michael
Published: December 2023

Introduction:
T-wave alternans (TWA) refers to the beat-to-beat variability in T-wave amplitudes or polarity on surface ECGs, and can signify susceptibility to malignant ventricular arrhythmias (VA).

Aims:
We present a case to emphasize the pathophysiology and clinical significance of this ECG finding.

Case description:
A 52 year-old female with history of HIV presents with shortness of breath and is treated for heart failure. In the ED, she has witnessed syncope and is found to have VT that progresses to VF. Resuscitation efforts are successful and include amiodarone loading. Figure 1A demonstrates baseline ECG on admission with a QTc of 495 ms. A few days later, an ECG reveals QTc of 696 ms with TWA (figure 1B). Shortly after, she develops polymorphic VT in the setting of long-short sequences and an R on T trigger (figure 1C) that is terminated with cardioversion. Review of pre-admission ECGs reveals that QTc prolongation occurred after initiation of a retroviral regimen that included rilpivirine and worsened with amiodarone. Both medications are discontinued, and she is eventually discharged with a QTc of 450 ms.

Early theories for TWA's mechanism hypothesized that dispersion of refractoriness resulted in depolarization through alternating pathways and thus this phenomenon. Recent understanding further suggests that TWA occurs as a result of cellular alternans and variation in action potential duration due to dysregulation of repolarization. If discordant repolarization alternans ensues, whereby neighboring cells repolarize in opposite phases (long-short, short-long), the resultant repolarization gradient and heterogeneity in cellular repolarization serves as the substrate for VA; if a premature beat encounters refractory myocardium and unidirectional block occurs, a re-entrant excitation tachycardia can be initiated.

Conclusions:
TWA on ECG suggests myocardial electrical instability as a result of cellular repolarization inhomogeneity.
Abstract 11821: Association of Hemoglobin With Mortality Outcomes in the Critical Care Cardiology Trials Network (CCCTN) Registry
Authors: Durowoju Rasheed , Chow Christine , Bohula Erin A , Berg David , Park Jeong-Gun , Morrow David , Kwon Younghoon ,   CCCTN Investigators
Published: December 2023

Introduction:
Anemia is common in critically ill patients and is a known risk indicator for poor outcomes. Little is known about the impact of anemia on short term outcomes in the setting of cardiac critical illness. We examined the association of varying degrees of anemia with in-hospital outcomes in cardiac intensive care unit (CICU) admissions.

Methods:
The Critical Care Cardiology Trials Network (CCCTN) is a multicenter network of tertiary CICUs in North America coordinated by the TIMI Study Group. During annual campaigns, each center contributes at least 2-mo of all consecutive medical CICU admissions. Admissions were stratified according to baseline hemoglobin (Hgb). The association of Hgb and in-hospital mortality, CICU length of stay and hospital length of stay was examined by logistic regression with multivariable adjustment.

Results:
Among 17,759 admissions, the median baseline Hgb was 12.0 g/dL (IQR 10.0, 13.8). Patients with lower Hgb tended to be older and female with lower body weight and a greater burden of comorbidities. After adjusting for sex and other relevant covariates, a lower baseline Hgb was associated with higher odds of in-hospital death (p-trend <0.0001), and longer CICU and hospital length of stay (p-trend <0.0001).

Conclusions:
Anemia is prevalent in half of patients admitted to the CICU. Lower Hgb level, even well above standard transfusion thresholds, is independently associated with higher in-hospital mortality and longer length of stay in cardiac critical illness.
Abstract 11955: Hospital Readmission Outcomes After Myocardial Infarction Among Patients With Myeloproliferative Neoplasms
Authors: Leiva Orly , Beaman Hannah , Brunner Andrew , How Joan , Hobbs Gabriela
Published: December 2023

Introduction:
Myeloproliferative neoplasms (MPNs) are chronic leukemias associated with increased risk of arterial and venous thrombotic events. Prior studies suggest patients admitted for acute myocardial infarction (AMI) with MPN have similar in-hospital outcomes but lower rates of invasive management compared with patients without MPN. However, post-hospital outcomes in this patient population have not been well characterized.

Methods:
Adult MPN patients with a primary admission of AMI from January 2017 to December 2018 were identified using the National Readmission Database. Propensity score matching (PSM) was performed to match 1 MPN for 10 non-MPN controls. Primary outcomes were 30-day all-cause, arterial thrombosis (AT)-related, cardiovascular (CV)-related, and bleeding-related readmissions.

Results:
After PSM, patient characteristics were well-balanced between groups (Table 1). MPN patients had similar rates of in-hospital mortality but higher rates of bleeding during index hospitalization. MPN patients had increased risk of 30-day all-cause, CV, and AT readmissions but not bleeding (Figure).

Conclusions:
Among patients hospitalized with AMI, those with MPN are associated with increased risk of CV and AT but not bleeding-related readmissions despite higher rates of index hospitalization bleeding. Further investigation is needed in order to improve post-AMI outcomes in patients with MPN.
Abstract 11982: Bariatric Surgery is Associated With Lower Odds of Cardiovascular Diseases and Cardiac Arrhythmias Among Hospitalized Patients With Non-Alcoholic Fatty Liver Diseases: A National Inpatient Sample Study
Authors: esparham ali , Shoar Saeed , Mehri Ali , modukuru venkat
Published: December 2023

Introduction:
Morbid obesity has shown a strong association with nonalcoholic fatty liver disease (NAFLD), both of which convey significant risk for the development of cardiovascular diseases (CVD). Bariatric surgery (BS) has proved to improve NAFLD and mitigate the severity of different CVD subgroups.

Research Question:
What are the odds of having different CVDs among morbidly obese patients with NAFLD who have undergone BS compared to those who have not.

Methods:
Using multivariate logistic regression, national inpatient sample (NIS) databased was analyzed from 2016 to 2019 to compare the odds of having CVD among NAFLD patients who have undergone BS and those who NAFLD patients with no prior BS.

Results:
The BS and non-BS groups consisted of 27,865 and 315,300 NALFD patients, respectively. BS group was significantly younger with a higher frequency of female patients.The white race, in contrast to the black race, was more frequently in the non-BS group. In addition, Medicare was significantly higher in the non-BS group compared to the BS group. BS was independently associated with lower odds of having HFpEF, HFrEF, AMI, stroke, CAD, peripheral vascular diseases, heart valve diseases, cardiac arrest, cardiogenic shock, AF, VF, VT, RBBB, LBBB, first-, second-, and third-degree heart block, complete heart block, and fascicular block (p-value<0.001 for all). After adjusting for demographics and medical comorbidities, BS was independently associated with 18% lower odds of in-hospital mortality (OR:0.82, CI 95% 0.69-0.97, p-value=0.018). The BS group had a significantly lower length of hospital stay (8.7 days vs. 10 days) (p-value<0.001).

Conclusion:
Bariatric surgery is associated with significantly lower odds of having cardiovascular diseases in-hospital mortality, and length of stay among hospitalized morbidly obese patients with NAFLD.
Abstract 12098: Evaluation of Inflammatory Biomarkers and Causal Association With Abdominal Aortic Aneurysm Development
Authors: Sharma Pranav , Yarmolinsky James , Karhunen Ville , Gill Dipender , Roychowdhury Tanmoy ,   AAAgen Consortium, Levin Michael , Damrauer Scott M
Published: December 2023

Introduction:
Observational analyses have linked circulating inflammatory biomarkers with an increased risk of abdominal aortic aneurysms (AAA). Although observational studies implicate inflammatory biomarkers in AAA, whether these are a cause or consequence of the disease is unknown. A limited number of trials have explored agents that reduce inflammation in slowing the progression of AAA. Observational study quality may be limited by residual confounding and reverse causality. We sought to leverage genetic instruments and Mendelian Randomization (MR) to evaluate the human genetic evidence supporting inflammatory biomarkers in the pathogenesis of AAA.

Methods:
We leveraged a meta-analysis of 6 genome-wide association studies (GWAS) of 66 circulating inflammatory markers including up to 59,969 participants of European ancestry. We tested the association for each biomarker with AAA using summary statistics from a meta-analysis of 17 individual GWAS from 14 discovery cohorts in the AAAgen consortium comprising 39,221 individuals with AAA. We employed Wald ratio or inverse-variance weighted MR; weighted median and weighted mode methods were applied as sensitivity analyses.

Results:
After accounting for multiple testing by controlling the false discovery rate (q < 0.05), we identified a total of 6/66 (9.1%) inflammatory biomarkers that had a significant association with AAA: sIL6R, CCL8, CCL7, ILRN, F2, and PIGF. These results were consistent across a range of linkage-disequilibrium thresholds to identify independent genetic instruments. Some of these biomarkers have been previously implicated in the development of AAA but have not been validated in human RCTs of aneurysm development, growth, or rupture.

Conclusions:
This analysis highlights the role of several circulating inflammatory markers in the development of AAA. These findings represent potential therapeutic targets for further investigation in mechanistic trials.
Abstract 12190: Cardiovascular Disease Mortality Trends Among Native Hawaiian and Pacific Islander Adults—United States, 2018 to 2022
Authors: Woodruff Rebecca C , Kaholokula Joseph K , Riley Lorinda , Loustalot Fleetwood V , Vaughan Adam , Diktonaite Kotryna , Richardson LaTonia C , Tong Xin
Published: December 2023

Introduction:
Native Hawaiian and Pacific Islander (NHPI) adults have historically been grouped with Asian adults in US mortality surveillance, potentially masking important differences between these two populations. In 2018, US death certificate race categories were modified, enabling the disaggregation of NHPI national CVD mortality surveillance data from the Asian population.

Methods:
Using National Vital Statistics System mortality data from 2018 to 2022, we identified CVD deaths among adults aged ≥35 years with ICD-10 codes I00-I99 listed as the underlying cause of death. Of all CVD decedents with non-Hispanic origin and NHPI listed alone or in combination with other race groups on the death certificate, we classified those with NHPI listed as the only race group as NHPI (60.1%). Rate ratios (RR) and 95% confidence intervals (CI) compared age-standardized mortality rates (ASMR) among NHPI adults compared to non-Hispanic Asian adults and US adults overall.

Results:
From 2018 to 2022, 6,088 CVD deaths (72.0% heart disease, 19.8% stroke) occurred among NHPI adults of Hawaiian (24.5%), Samoan (24.3%), Guamanian (11.0%), or other Pacific Islander (40.2%) descent. The NHPI ASMR was 464.5 CVD deaths per 100,000 (95% CI: 452.4-476.6), second only to the non-Hispanic Black ASMR (590.3 CVD deaths per 100,000, CI: 588.7-591.8; Figure). The ASMR among NHPI adults was significantly higher than non-Hispanic Asian adults (RR: 1.86, CI: 1.81-1.91) and US adults overall (RR: 1.07, 95% CI: 1.04-1.10).

Conclusions:
Single-race NHPI adults had the second-highest CVD death rate in the US from 2018 to 2022, second only to Black adults, and significantly higher than Asian adults. Surveillance using broader multi-race definitions to identify the NHPI population, further disaggregate by NHPI subgroup, and explore geographic variation is needed to better understand potential health disparities and target interventions to reduce CVD mortality disparities among NHPI adults.
Abstract 12315: Healthcare Resource Utilization and Costs Associated With New York Heart Association Functional Class in Patients With Obstructive Hypertrophic Cardiomyopathy in the United States
Authors: Wang Yan , Gao Weihua , Gao Sophie , Dubey Anand , Han Xu
Published: December 2023

Background:
In obstructive hypertrophic cardiomyopathy (HCM), New York Heart Association (NYHA) class has been associated with increased risks of adverse cardiovascular (CV) outcomes that may require more intensive healthcare.

Research Question:
Is NYHA class associated with healthcare resource utilization (HCRU) and costs in obstructive HCM?

Aims:
To describe all-cause and CV-related HCRU and costs by NYHA class in obstructive HCM.

Methods:
This was a retrospective cohort study of adults with obstructive HCM and ≥1 documented NYHA class in Optum’s de-identified Market Clarity database (administrative claims linked with electronic health records [EHR]) from 1/1/2017 to 3/31/2022. Index date was the date of the first NYHA class (i.e., index NYHA class) on or after the earliest date for diagnosis of obstructive HCM or, if any, septal reduction therapy. Annualized all-cause and CV-related HCRU and costs, overall and stratified by the index NYHA class, were assessed using claims during the 182 days after index (i.e., follow-up). Costs were adjusted to 2022 USD.

Results:
A total of 754 patients were included, with 20.0%, 44.0%, 30.2%, and 5.7% having NYHA class I, II, III, and IV at index, respectively (
Table
). The annual number of all-cause hospitalizations increased with higher index NYHA classes (mean ± SD 0.3 ± 1.0, 1.0 ± 1.8, 1.6 ± 2.6, and 2.1 ± 2.8 for class I, II, III, and IV, respectively). A similar trend was observed for emergency room visits, outpatient visits, and other visits. The total all-cause costs were higher for patients with worse index NYHA classes (mean ± SD $35,339 ± 64,594, $62,899 ± 86,765, $77,727 ± 109,519, and $123,058 ± 139,867 for class I, II, III, and IV, respectively). CV-related HCRU and costs were also generally higher for patients with a worse index NYHA class.

Conclusion(s):
Obstructive HCM was associated with a substantial economic burden. A worse NYHA class was associated with higher all-cause and CV-related HCRU and costs in obstructive HCM.
Abstract 12316: Metrnl Deficiency Destabilized the Atherosclerotic Plaque and Increased the Risk of Acute Coronary Syndrome
Authors: Huang Rong , Lai Fengling , Hou Siyu
Published: December 2023

Introduction:
Metrnl has been recently identified as a myokine/adipokine that acts as an immune/metabolic regulator.

Hypothesis:
Metrnl might be exert an important role in acute coronary syndrome.

Methods:
Circulating Metrnl levels were evaluated in 983 subjects with acute coronary syndrome and healthy controls recruited from Jinan Central Hospital. Apolipoprotein E-deficient mice infected with Metrnl-silencing adenovirus were used for investigating the function of Metrnl in atherosclerotic plaques. The relevant molecular mechanisms were then explored in-vitro in siMetrnl transfected and Metrnl treated HUSMC cells.

Results:
We found circulating Metrnl levels were significantly decreased in patients with ACS as compared to healthy controls. Metrnl were inversely associated with the incident and recurrent risk of acute coronary syndrome after adjustment for traditional risk factors. Metrnl inhibition in HFD-fed ApoE-/- mice resulted in aggravated atherosclerotic lesions with an SMC-poor/macrophage-rich fibrous cap. Further study demonstrated that Metrnl downregulation increased whereas overexpression prevented SMCs apoptosis and lipid trans-differentiation. KIT/SRC/AKT signaling pathway is involved in the role of Metrnl for the regulation of SMCs fate.

Conclusions:
Our findings demonstrated that decreased circulating Metrnl levels might be a potential biomarker for identification of patients with increased risk of acute coronary syndrome. Metrnl protected against apoptosis and lipid trans-differentiation in SMCs and stabilized the atherosclerotic plaque, suggesting a potential target for the treatment of atherosclerosis.
Abstract 12408: Response to Mavacamten by Sarcomere Gene Mutation Status in EXPLORER-HCM
Authors: Ho Carolyn Y , Garcia-Pavia Pablo , Lakdawala Neal K , Owens Anjali T , olivotto iacopo , Gimeno Blanes Juan Ramon , Rincon Luis M , Owens David S , Charron Philippe , Cardim Nuno , Sehnert Amy J , Anderson Warren , Landis Jessica , Wang Zhaoqing , Barriales-Villa Roberto
Published: December 2023

Background:
Mavacamten is a small molecule inhibitor of cardiac myosin that was developed based on insights into the molecular basis of hypertrophic cardiomyopathy (HCM). In the phase 3 EXPLORER-HCM trial (NCT03470545), patients showed consistent benefit in the primary endpoint with mavacamten treatment vs placebo while subgroup analysis of patients with pathogenic or likely pathogenic variants in a broad panel of HCM-related genes, revealed a slightly more favorable response. However, it is unknown how patients specifically with sarcomere gene variants responded.

Aims:
To assess the effect of HCM-specific sarcomere gene variants on response to mavacamten.

Methods:
Sequencing using a 60 gene panel (Invitae) was optional in EXPLORER-HCM. In this exploratory analysis, responses to mavacamten vs placebo for the primary, secondary, and exploratory endpoints were analysed. Patients were grouped based on sarcomere gene variant status (positive for pathogenic/likely pathogenic/variants of uncertain significance [SARC+], negative [SARC–]) or no sequencing). Analyses were adjusted for clinically relevant variables.

Results:
Of 190/251 patients sequenced, 73 were SARC+ (mavacamten, n = 33; placebo, n = 40), 117 were SARC– (mavacamten, n = 57; placebo, n = 60) and 61 had no panel sequencing (mavacamten, n = 33; placebo, n = 28). Mavacamten treatment showed a favorable response for the primary endpoint vs placebo, for SARC+ (odds ratio [OR], 4.43 [95% CI, 1.56-12.58]), and for SARC– (OR, 2.52 [95% CI, 0.99-6.42]) (
Figure
). Improvements with mavacamten vs placebo were observed in both SARC+ and SARC– subgroups for change from baseline to week 30 in post-exercise left ventricular outflow tract gradient, and peak oxygen consumption, and in New York Heart Association class.

Conclusions:
In this exploratory subgroup analysis, mavacamten treatment benefit was observed both in patients with and without sarcomere gene variants.
Abstract 12444: Pulse Pressure and Cardiovascular and Renal Outcomes by Age in the Chronic Renal Insufficiency Cohort
Authors: Fischman Clara , Townsend Raymond R , Cohen Debbie L , Rahman Mahboob , Weir Matthew R , Juraschek Stephen P , South Andrew , Appel Lawrence J , Drawz Paul , Cohen Jordana ,   CRIC Study Investigators
Published: December 2023

Pulse pressure (PP) is associated with cardiovascular events and the progression of chronic kidney disease (CKD) to end stage kidney disease (ESKD). While PP is known to widen with age, it is less clear what other clinical factors affect PP and whether the risks associated with wide PP are the same across all ages. We used Cox proportional hazards models to investigate the association of PP with development of 1) atherosclerotic cardiovascular disease (ASCVD) events (congestive heart failure hospitalization, myocardial infarction, stroke and peripheral artery disease) or death and 2) 50% reduction in estimated glomerular filtration rate (eGFR) or ESKD in the Chronic Renal Insufficiency Cohort (CRIC) Study. In sensitivity analyses, we evaluated the association of time-updated PP with these outcomes, accounting for potential time-updated confounders using inverse probability of treatment weighting. We evaluated for effect modification by age (divided into tertiles), apparent treatment-resistant hypertension (HTN), baseline diabetes mellitus (DM) status, baseline CKD stage and baseline cardiovascular disease (CVD). Among 5,621 participants with CKD followed for ~5.4 years, mean PP was 57±19 mmHg, 1,396 (25%) had an ASCVD event, 1,186 (21%) died and 1,783 (32%) participants experienced the composite renal outcome. Every 10 mm Hg wider PP was associated with 6% higher risk of an ASCVD event or death (time-updated adjusted hazard ratio [HR]=1.06, 95% CI 1.04, 1.08) and 17% higher risk of the composite renal outcome (time-updated adjusted HR=1.17, 95% CI 1.16, 1.18). Wider PP was associated with a higher risk of ASCVD events or death among participants in the lowest age tertile (21-61 years;
Figure 1A
), but a higher risk of the composite renal outcome in the oldest age tertile (71-79 years;
Figure 1B
), suggesting PP may be associated with different pathophysiology across ages.
Abstract 12712: Safety of Latex Containing Swan-Ganz Catheters in Patients With Cutaneous Hypersensitivity to Latex
Authors: Houtz Brady , Round Kellen J , Slota Paul J , Scharf Michael L , Ford Megan K , Fischman David L , shah mahek , Ruggiero Nicholas J , Vishnevsky Alec , Price Jordan , Savage Michael P
Published: December 2023

Introduction:
Hypersensitivity to latex is common. Balloon-tipped right heart catheters are typically made from latex. Latex-free catheters while available have limitations including the need for large sized vascular sheaths. It is unknown if latex balloon catheters can be safely used in patients who have cutaneous reactions to latex.

Goals:
The goal of this study was to assess the safety of using latex-containing catheters for right heart catheterization (RHC) in patients with a prior history of cutaneous allergy to latex.

Methods:
Electronic medical records and cardiac catheterization procedure database identified 127 consecutive patients with a history of cutaneous hypersensitivity (rash, urticaria) to latex who underwent RHC with balloon-tipped catheters. Patients with known anaphylaxis to latex were excluded. The primary outcome was the occurrence of periprocedural hypersensitivity reactions. Outcomes of patients with latex-containing catheters (LC Group, n=99) were compared to patients with latex-free catheters (LF Group, n=28).

Results:
The study population consisted of 28 men and 99 women, aged 65
+
14 years. Indications for RHC were heart failure in 48 (38%), pulmonary hypertension in 25 (20%), cardiomyopathy in 19 (15%), valvular heart disease in 19 (15%), unexplained dyspnea in 13 (10%), and heart transplant in 2 (2%). LC and LF patients had comparable demographics, cardiac risk factors, and indications for RHC. In-body catheter exposure times in the LC and LF groups were 8.6
+
5.0 and 9.7
+
6.1 minutes, respectively (p=ns). Venous sheath sizes were smaller in the LC group; sheaths
<
5 Fr were used in 52/99 (53%) of the LC group vs. 0/28 in the LF group (p<0.001). Antecubital vein access was used in 42/99 (42%) of the LC group but in none of the LF group (p<0.001). There were no procedural hypersensitivity reactions in either the LC or LF groups. Repeat procedures were common; in total, 149 RHC were performed using latex catheters with no reactions.

Conclusions:
In patients with a history of non-anaphylactic cutaneous hypersensitivity to latex, the use of latex balloon-tipped catheters was not associated with allergic reactions. Latex catheters offer technical advantages including smaller sized vascular sheaths and more options for venous access.
Abstract 12721: Myocardial DNA Damage Predicts Heart Failure Outcome in Various Underlying Diseases
Authors: Dai Zhehao , Ko Toshiyuki , Nomura Seitaro , Fujita Kanna , Inoue Shunsuke , Onoue Kenji , Amiya Eisuke , Hatano Masaru , Takeda Norifumi , Morita Hiroyuki , Saito Yoshihiko , Komuro Issei
Published: December 2023

Background:
Responses to treatment for heart failure vary widely, and a reliable predictor has been long awaited.

Aims:
To investigate the relationship between DNA damage in myocardial tissue and treatment response and prognosis of heart failure.

Methods:
In this multicenter cohort study including patients with heart failure with reduced ejection fraction (HFrEF) of various underlying etiologies, we performed immunostaining of DNA damage markers, poly(ADP-ribose) (PAR) and γ-H2A.X on endomyocardial biopsy specimens. We calculated the percentage of nuclei positive for each DNA damage marker as %PAR and %γ-H2A.X. The primary outcome was left ventricular reverse remodeling (LVRR) at 1 year, and the secondary outcome was a composite of cardiac death, heart transplantation, and ventricular assist device implant. Inverse probability weighted method was used to restore the balance of baseline variables.

Results:
Of the 175 included patients with a mean age at 56 years and a median follow-up of 1213 days, 72% were male, and 55% achieved LVRR. A lower DNA damage marker positivity was associated with a higher probability of achieving LVRR [OR per 10 increase in %PAR 0.07 (95%CI 0.03–0.17); OR per 10 increase in % γ-H2A.X 0.40 (95%CI 0.29–0.55)]. There was a negative correlation between the average degree of DNA damage and the probability of LVRR, across different underlying diseases. Patients with higher %PAR or %γ-H2A.X had more long-term clinical events [HR per 10 increase in %PAR 1.63 (95%CI 1.31-2.01); HR per 10 increase in %γ-H2A.X, 1.48 (1.27-1.72)]. Of the 41 patients who consented on whole exome sequencing, those with non-sarcomere gene mutations (LMNA, etc; 10 patients) had a higher degree of DNA damage than those with sarcomere gene mutations (TTN, etc; 4 patients).

Conclusions:
DNA damage determines the consequences of heart failure. Assessment of DNA damage is useful to predict treatment efficacy and prognosis of patients with HFrEF of various underlying etiologies.
Abstract 12725: Day of the Week Variation of Unexpected Sudden Cardiac Death
Authors: Latola Hanna , Pakanen Lasse , Ukkola Olavi , Junttila Juhani , Huikuri Heikki , Perkiomaki Juha
Published: December 2023

Introduction:
Data on day of the week (septadian) variation of unexpected sudden cardiac death (SCD) are limited.

Methods:
We evaluated the incidence of unexpected SCD on different days of the week in a consecutive series of 5,869 SCD victims from Northern Finland [the Fingesture study (Finnish Genetic Study of Arrhythmic Events)]. A medico-legal autopsy was performed on all unexpected sudden death victims as it is mandatory in Finland. The autopsies were performed between the years 1998-2017.

Results:
The incidence of unexpected SCD in the region of Northern Finland with approximately 600,000 inhabitants on average was 55 per 100,000 inhabitants per year. The mean incidence of unexpected SCD was higher during the days form Friday to Sunday (peaking on Saturday) than during the days from Monday to Thursday (8.54±0.72 vs. 7.22±0.19 SCDs per day of the week per 100,000 inhabitants per year, p<0.001, respectively) (Figure 1). The number of unexpected SCD victims with alcohol in blood was higher during the days form Friday to Sunday (peaking on Saturday) than during the days from Monday to Thursday (Figure 2).

Conclusion:
The incidence of unexpected SCD was highest during the days form Friday to Sunday, peaking on Saturday. There was a similar distribution of the number of SCD victims with alcohol in blood during the days of the week, suggesting that alcohol drinking with its adverse influences contributes to the septadian variation of unexpected SCD.
Abstract 12726: Novel, Potent, and Highly Selective Calcium/Calmodulin-Dependent Protein Kinase II (CaMKII) Inhibitors Reduce Substrate Phosphorylation in Rat Hearts and Prolong Survival in a Mouse Model of Severe Heart Failure
Authors: Takagahara Shuichi , Harada Mioko , Asada Mari , Harada Masataka , Hirakata Masao , Surks Howard K , Mendelsohn Michael , Ikeda Shota
Published: December 2023

Introduction:
CaMKII is a target of longstanding interest in drug development and has been validated in multiple preclinical models of heart failure, as well as in arrhythmia diseases, including catecholaminergic polymorphic ventricular tachycardia and atrial fibrillation. We describe here the pharmacological profiles of a novel oral CaMKII inhibitor, CRD-2015. We demonstrate the ability of CRD-2015 to reduce substrate phosphorylation in rat hearts, and to strongly prolong survival in the calsequestrin transgenic (CSQ-Tg) mouse model of severe heart failure.

Results:
CRD-2015 is a potent (IC
50
0.62nM), highly selective CaMKII inhibitor. Oral administration of CRD-2015 dose-dependently decreased phospholamban (P-PLN) and ryanodine receptor 2 (P-RyR2) phosphorylation at their CaMKII-specific sites (Thr17 and Ser2814, respectively) in normal rat hearts, with strong correlation between the plasma concentrations (PK) and the reduction in phosphorylation (PD) (Figure, A). In CSQ-Tg mice, CRD-2015 also decreased cardiac P-PLN and P-RyR2 in a dose-dependent manner. Chronic administration of CRD-2015 prolonged survival in a dose-dependent manner (Figure, B). At the maximum dose level, all CSQ-Tg mice survived for 27 days (n=15/15) with the treatment of CRD-2015, while no mice survived past 24 days in the vehicle-treated group (n=0/15). Similar dose and concentration-dependent reductions in P-PLN and P-RyR2 and prolongation of survival in CSQ-Tg mice were also detected with a second potent (IC
50
0.40nM) and selective CaMKII inhibitor, CRD-2959.

Conclusions:
Our novel CaMKII inhibitor, CRD-2015 shows a clear PK/PD relationship in normal rats and prolongs survival in a mouse model of severe heart failure. These results demonstrate the successful creation of specific CaMKII inhibitors with efficacy in preclinical models and support their clinical development for the treatment of heart failure and other cardiovascular diseases.