tbuckley/cabot-search huggingface dataset:
Abstract 13142: Combined Treatment With Dapagliflozin and Exenatide is More Cardioprotective Than Either Agent Alone in a Non-Diabetic Mouse Model of Ischemia-Reperfusion Injury
Authors: Dorrin Zarrin Khat, Muhammad A Siraj, Abdul Momen, Uros Kuzmanov, Meghan McFadden, Frank Shin-Haw Lee, Sina Hadipour-Lakmehsari, Anthony Gramolini, Mansoor Husain
Journal: Circulation (2021)

Introduction: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1RA) have individually shown cardiovascular benefits in patients with type 2 diabetes (T2D). SGLT2i also reduced events in patients with reduced ejection fraction heart failure, with or without T2D. However, it is not known whether the cardiovascular effects of SGLT2i and GLP-1RA are through shared or distinct mechanisms, and whether combining these agents would confer additive cardioprotection against ischemia-reperfusion injury (IRI) in the absence of diabetes. Methods &amp; Results: Non-diabetic male C56BL/6-J mice randomized to 7-d treatment with SGLT2i dapagliflozin (Dapa) and/or GLP-1RA exenatide (Ex-4) or vehicle-controls underwent IRI via 30-min left anterior descending (LAD) artery ligation. Analysis of late cardiac remodeling at d-28 post-IRI revealed preserved ejection fraction (EF) in mice treated with Dapa+Ex4 (50±2%; n=12, P&lt;0.05) vs. vehicle-treated controls (36±3; n=11, P&lt;0.05), whereas treatment with Dapa- and Ex-4-alone showed no such benefit. These improvements in LV function were associated with reduced infarct size (%LV) in mice treated with Dapa+Ex4 (17±3; n=8, P&lt;0.001) and Ex-4-alone (29±3; n=10, P&lt;0.05) vs. vehicle-control (44±5; n=10). Metabolome and merged proteome+phosphoproteome analyses revealed systemic and myocardial metabolic modulation following 7-d Dapa+Ex-4 treatment, with distinct enrichment of mitochondrial electron transport chain pathways. Cardiomyocytes isolated from mice treated in vivo for 7-d also showed enhanced aerobic respiration as measured by oxygen consumption rate (OCR;17.6±1.7 pmol/min/μg protein; n=4 mice) compared Dapa- (8.9±0.8; n=3, P&lt;0.001), Ex-4-alone (11.4±0.9; n=3, P&lt;0.01) and vehicle-treated controls (9.5±0.6; n=5, P&lt;0.001). Conclusions: Combined therapy with SGLT2i+GLP-1RA in non-diabetic mice better prevented late cardiac remodeling after IRI compared to either agent alone or vehicle controls. These findings provide rationale for the combined use of these agents in a condition (IRI) for which there remains no approved therapy, and implicate metabolic modulation as a cardioprotective strategy in the absence of diabetes.
Association of HLA-B∗35 and moderate or severe cutaneous reactions secondary to benznidazole treatment in chronic chagas disease
Authors: Pau Bosch-Nicolau, Fernando Salvador, Adrián Sánchez-Montalvá, Clara Franco-Jarava, Iria Arrese-Muñoz, Elena Sulleiro, Silvia Roure, Lluis Valerio, Inés Oliveira-Souto, Núria Serre-Delcor, Diana Pou, Begoña Treviño, María L. Aznar, Juan Espinosa-Pereiro, Israel Molina
Journal: Clinical Microbiology and Infection (2021)
The Impact of Pacritinib on Myelofibrosis Symptoms in Patients with Moderate and Severe Thrombocytopenia: A Retrospective Analysis of Patients in the Persist-2 Study
Authors: Jeanne M. Palmer, Ruben A. Mesa, Stephen T. Oh, Raajit Rampal, Sarah A Buckley, Karisse Roman-Torres, Srdan Verstovsek, John Mascarenhas, Alessandro M. Vannucchi, Jean-Jacques Kiladjian, Claire N. Harrison, Prithviraj Bose, Adam R Craig, Aaron T. Gerds
Journal: Blood (2021)
Abstract 9939: Admission Systolic Blood Pressure and Left Ventricular Structure/ Hemodynamics in Patients with Acute Decompensated Heart Failure with Preserved Ejection Fraction
Authors: Katsuomi Iwakura, Toshinari Onishi, Masato Okada, Nobuaki Tanaka, Yasushi Koyama, ATSUNORI OKAMURA, Kenshi Fujii, Masahiro Seo, Masamichi Yano, Takaharu Hayashi, Akito Nakagawa, Yusuke Nakagawa, Shunsuke Tamaki, Takahisa Yamada, Yoshio Yasumura, Shungo Hikoso, Yohei Sotomi, Yasushi Sakata
Journal: Circulation (2021)

Introduction: The blood pressure at hospital admission is associated with prognosis in patients with acute decompensated heart failure (ADHF). It is not well elucidated how admission blood pressure is determined and how it can affect clinical outcomes in patients with heart failure with preserved ejection fraction (HFpEF). Hypothesis: Difference in left ventricular (LV) structure and function could be associated with admission systolic blood pressure (sBP) in patients with decompensated HFpEF. Methods: The PURSUIT-HFpEF (Prospective, Multicenter, Observational Study of Patients with Heart Failure with Preserved Ejection Fraction) is a multicenter registration of patients hospitalized for acute decompensated HFpEF. We divided the registered patients based on “clinical scenario (CS)” in ADHF, as CS1;sBP&gt;140mmHg at admission, CS2; sBP 100-140mmHg, CS3; sBP &lt;100mmHg. Echocardiography was performed during hospital stay. We followed them to observe the major adverse cardiovascular events (MACE; composite of death, heart failure hospitalization and stroke) for median of 390 days (IQR 253 to 7272 days). Results: Among 893 patients (age 81±9 years, male gender 45.2%) who were enrolled for the present study, only 14 patients (1.6%) were categorized as CS3. Thus, we combined patients with CS2 and CS3 into the CS2/3 group (n=383). No difference was observed in age and risk factors except gender (CS1; 49.0% vs. CS2 40.2% of male, p=0.001). Cox proportional hazard model showed admission sBP was an independent predictor of MACE (p=0.0001) along with age and presence of chronic kidney disease, and the CS2/3 had higher incidence of MACE during follow-up period than CS1 (p=0.0001 by log-rank test). While there was no differences in LV ejection fraction, the CS2/3 group showed smaller LV dimension (45±6mm vs. 46±6mm, respectively, p=0.0004) and volume (78±31 ml vs. 86±36mm, p=0.008) at end-diastole, and lower cardiac output (3.9±1.4 ml/min vs. 4.1±1.4 ml/min, p=0.0001) than the CS 1. No difference was observed in diastolic parameters such as left atrial volume index or E/e’ ratio between two groups. Conclusions: Smaller LV volume and lower cardiac output was associated with lower admission sBP, which led to poorer prognosis, in patients with decompensated HFpEF.
Abstract 10440: Independent Prognostic Utility of <sup>11</sup> C-Pittsburgh Compound B Positron Emission Tomography in Light Chain Cardiac Amyloidosis Patients
Authors: You-Jung Choi, Youngil Koh, Hyun-Jung Lee, In-chang Hwang, Jun-bean Park, Yeonyee E Yoon, Hyung-kwan Kim, Yong-Jin Kim, Goo-yeong Cho, Dae-won Sohn, Jin Chul Paeng, Seung-pyo Lee
Journal: Circulation (2021)

Introduction: Recent advances in nuclear molecular imaging have allowed a more specific, non-invasive approach to the diagnosis and prognostication of cardiac amyloidosis (CA). 11 C-Pittsburgh compound B positron emission tomography/computed tomography (PiB PET/CT) is one of the widely studied nuclear molecular imaging. However, it remains to be verified whether it has any independent additional prognostic value. Hypothesis: 11 C-PiB PET/CT would have independent prognostic value in patients with light chain CA (ALCA). Methods: A prospective cohort study of 58 consecutive patients with ALCA who underwent 11 C-PiB PET/CT, were stratified into 2 groups based on a myocardial 11 C-PiB uptake or not on PET/CT. The primary and secondary outcomes were all-cause death and cardiovascular death, respectively. Results: During a median 13.6 month follow-up, 29 patients died, of which 12 died from cardiovascular events. Patients with positive 11 C-PiB PET uptake had worse event-free survival from all-cause deaths (60.5% vs. 28.7%, P =0.001) and cardiovascular deaths (84.9% vs. 58.5%, P =0.001). A positive myocardial 11 C-PiB PET/CT was an independent predictor for all-cause death (adjusted hazard ratio [aHR] 4.143, 95% confidence interval [95%CI] 1.243-13.816, P =0.021) and cardiovascular death (aHR 5.598, 95%CI 1.060-29.560, P =0.043). When 11 C-PiB PET/CT was combined with troponin I and N-terminal probrain Natriuretic Peptide, the performance of prediction significantly improved by net reclassification index of 0.872 and by integrated discrimination improvement statistics of 0.177. Conclusions: 11 C-PiB PET/CT is a strong independent predictor for all-cause and cardiovascular mortality, and provides incremental prognostic benefits in patients with ALCA. Further investigations are warranted on whether PET/CT should be included in the risk stratification for the ALCA patients
Abstract 10270: Association Between Hypertension and Aortic Stenosis Mortality in a Large Unselected Hospital Population
Authors: Jonathan Brown, David Kent, Norma Terrin, Jonathan Kusner, Benjamin S Wessler, Elazer R Edelman
Journal: Circulation (2021)

Introduction: Hypertension (HTN) is common for patients with AS. However, whether it is a sign of a healthy ventricle and therefore a good prognostic sign, or a risk factor remains unclear. We sought to evaluate the effect of HTN on survival in AS patients at a large referral center. Methods: Echocardiograms conducted at Tufts Medical Center (Boston, MA) were screened and parameters were extracted from a central database. NLP was used on unstructured clinical visit notes to fill in missing data. AS severity was defined as [mild (Vmax: 2.5- 2.9 m/s, MG: 10-20 mmHg, AVA: &gt; 1.5 cm2), moderate (Vmax: 3.0-3.9, MG: 20-40, AVA: 1.0-1.5) or severe (Vmax: &gt; 4.0, MG: &gt; 40, AVA: &lt; 1.0)]. Cox proportional hazard regression models assessed the association between hypertension stage [Normotensive: SBP &lt; 120 mmHg, Elevated: SBP 120-129 mmHg, Stage 1: 130-139 mmHg, Stage 2: &gt; 140 mmHg] taken at the time of the echocardiographic exam and death. Models were adjusted for age, sex, ejection fraction, BMI, and degree of mitral regurgitation. The last echocardiographic time point prior to death or being censored alive was used for modeling. Results: Of the 160,491 echocardiographic exams performed between 2006-2021 2,699 had mild AS or greater. Patients were followed for a median of 533 days for mild (N = 319), 593 days for moderate (N = 1070), and 76 days for severe (N = 1310). Overall mortality was lowest for moderate and severe AS (log-rank test: P &lt; 0.001). HTN was associated with decreased mortality relative to a normotensive state at moderate (HR: Elevated 0.67 CI: 0.35-1.26, Stage 1 0.35 CI: 0.19-0.63, Stage 2 0.52 CI: 0.31-0.87) and severe stenosis (HR: Elevated 0.64 CI: 0.25-1.59, Stage 1 0.29 CI: 0.12-0.66, Stage 2 0.42 CI: 0.22-0.81). Conclusions: Contrary to other cardiovascular diseases HTN was associated with decreased mortality for this large cohort with significant AS. This observation raises questions about whether traditional HTN treatment targets are appropriate for patients with AS.
Abstract 10483: Dose Of Outpatient Cardiac Rehabilitation After Acute Coronary Syndrome
Authors: Koshiro Kanaoka, Yoshitaka Iwanaga, michikazu nakai, Yuichi Nishioka, Tomoya Myojin, Shinichiro Kubo, Katsuki Okada, Tsunenari Soeda, Tatsuya Noda, Yasushi Sakata, Yoshihiro Miyamoto, Tomoaki Imamura, Yoshihiko Saito
Journal: Circulation (2021)

Introduction: Cardiac rehabilitation (CR) is an effective intervention associated with a reduction in mortality and re-hospitalization for patients with acute coronary syndrome (ACS), but CR programs have not been fully implemented and doses are varied across patients. Hypothesis: This study aims to reveal the current practice of outpatient CR, and investigate the association between dose and long-term mortality for patients with ACS in real-world settings. Methods: We performed a nationwide retrospective cohort study using the National Database of Health Insurance Claims and Specific Health Checkups of Japan. Patients with ACS underwent percutaneous coronary intervention between April 2014 and March 2018 and outpatient CR within 180 days after admission were included. Results: Of all 202,320 patients underwent percutaneous coronary intervention for ACS, a total of 20,444 (10%) patients underwent outpatient CR. The median (IQR) number of total CR sessions was 9 (3-17) times, and the median (IQR) duration per session was 3.0 (2.1-3.0) units. Patients were divided into four groups according to the total session number (≤9 or 10≤ times) and duration per session (≤40 or 60≤ minutes). Of 20,444 patients, 3,845 patients were assigned in low-number/short-duration, 6,976 patients in low-number/long-duration, 1,874 patients in high-number/short-duration, and 7,749 patients in high-number/long-duration group, respectively. After adjustment for age, sex, infarction site, comorbidities, and treatments during hospitalization, the adjusted HR for all-cause mortality was 1.01 (95% CI: 0.80-1.26, p=0.95) in low-number/long-duration group, 0.62 (95% CI: 0.45-0.86, p=0.004) in high-number/short-duration group, 0.74 (95% CI: 0.59-0.92, p=0.007) in high-number/long-duration group, compared with low-number/short-duration group. Conclusions: The participation rate of outpatient CR after ACS was low and the doses of sessions were varied in real-world settings. Higher number of total sessions in outpatient CR was associated with a better prognosis despite the session duration.
Epigenetic profiling of twins identify repression of KLF4 as a novel pathomechanism in systemic sclerosis
Authors: Jörg H W Distler, Steven O'Reilly
Journal: Annals of the Rheumatic Diseases (2021)

Systemic sclerosis (SSc) is an idiopathic autoimmune connective tissue disease with vascular abnormalities, inflammation and fibrosis. The fibrosis affects the skin as well as several internal organs. An incomplete understanding of the pathways that govern activation of the cells involved in disease pathogenesis has hampered new therapies. In this issue of Annals of the Rheumatic Diseases, Malaab et al (REF to be inserted by ARD) employ a unique cohort of 15 twins disconcordant for the diagnosis of SSc to demonstrate a key role of epigenetics including methylation, alterations of microRNA and ultimately dysregulation of Kruppel-like factor 4 (KLF4) that impacts on fibrosis. This sheds light on underlying epigenetic mechanisms and exposes a new therapeutic target.

Epigenetics is the study of heritable changes in gene expression not mediated by changes in the DNA sequence itself. Three main mechanisms mediate epigenetic changes: non-coding RNAs, DNA methylation and histone modifications.1 DNA and the cytosine base of DNA can be modified by the addition of a methyl group by a family of three DNA methyltransferases enzymes on the fifth carbon of cytosine. This modification enables binding of DNA methylation proteins such as methyl binding domain proteins, which in turn recruit histone modifying proteins and other epigenetic modulators that ultimately represses gene expression. Non-coding RNAs are defined as a long or short set arbitrarily defined by length. In the case of microRNAs, they regulate gene expression by binding the 3’UTR of mRNA that leads to gene repression. Long non-coding RNAs are usually much longer and regulate gene expression, both positively and negatively, through only partially unknown mechanisms. Finally, alteration in the histone tails of …
Detection Rate of Integrated Molecular and Cytogenetic Biomarker Testing for Chronic Lymphocytic Leukemia
Authors: Ramadevi Prathapam, Najuma Maharjan, Sheila B Powers, Tracey Allen K Freitas, Guoli Sun, Zheng Tan, Saurabh K Gupta, Vishwanathan Hucthagowder, Jennifer A Graham, Stacey L Whitman, Sushant Khadgi, Sugganth Daniel, Frederick K. Racke, Kristen J Champion
Journal: Blood (2021)
Nanoparticles with rough surface improve the therapeutic effect of photothermal immunotherapy against melanoma
Authors: Jiao Xue, Yining Zhu, Shuting Bai, Chunting He, Guangsheng Du, Yuandong Zhang, Yao Zhong, Wenfei Chen, Hairui Wang, Xun Sun
Journal: Acta Pharmaceutica Sinica B (2021)

Photothermal therapy has been intensively investigated for treating cancer in recent years. However, the long-term therapeutic outcome remains unsatisfying due to the frequently occurred metastasis and recurrence. To address this challenge, immunotherapy has been combined with photothermal therapy to activate anti-tumor immunity and relieve the immunosuppressive microenvironment within tumor sites. Here, we engineered silica-based core‒shell nanoparticles (JQ-1@PSNs-R), in which silica cores were coated with the photothermal agent polydopamine, and a bromodomain-containing protein 4 (BRD4) inhibitor JQ-1 was loaded in the polydopamine layer to combine photothermal and immune therapy for tumor elimination. Importantly, to improve the therapeutic effect, we increased the surface roughness of the nanoparticles by hydrofluoric acid (HF) etching during the fabrication process, and found that the internalization of JQ-1@PSNs-R was significantly improved, leading to a strengthened photothermal killing effect as well as the increased intracellular delivery of JQ-1. In the animal studies, the multifunctional nanoparticles with rough surfaces effectively eradicated melanoma via photothermal therapy, successfully activated tumor-specific immune responses against residual tumor cells, and further prevented tumor metastasis and recurrence. Our results indicated that JQ-1@PSNs-R could serve as an innovative and effective strategy for combined cancer therapy.
Abstract 10636: Inter-Arm Difference in Systolic Blood Pressure: Prevalence and Associated Factors in an African Population
Authors: Gwladys GBAGUIDI, Audrey KABOURE, Yessito Corine NadÃ¨ge Houehanou, Salimanou AMIDOU, Dismand HOUINATO, Victor Aboyans, Philippe LACROIX
Journal: Circulation (2021)

Background: Systolic inter-arm blood pressure differences (IABPD) is associated with increased cardiovascular mortality and morbidity. However, almost all data are issued from western countries, and the epidemiology and associated risk factors of IABPD in sub-Saharan Africa is unknown. Objectives: This study aims to determine the descriptive epidemiology of IABPD in a rural community of Benin. Methods: A cross-sectional study was conducted among participants of the TAnve HEalth Study (TAHES), a prospective population-based cohort conducted in Benin since 2015. All inhabitants of two villages (Tanve and Dékanme), aged 25 years and over were included. Pregnant woman and participants unable to answer the questions were excluded from the study. Data were collected from February to March, 2020 using the WHO STEPS adapted questionnaire in a systematic door-to-door survey. Brachial BP were recorded at rest on both arm with an electronic device. Three series of BP measures were collected sequentially. On each arm the average of the two last measurements was used for analysis. High IABPD was defined as the absolute value of the difference in systolic BP between the left and right arms ≥ 10 mmHg. A multivariate logistic regression models identified factors associated with IABPD. Results: A total of 1,505 participants (median age 40 [32-54] years, 59.3% women) were included in this study. The prevalence of systolic IABPD was 19% (95%CI: 17-21). The prevalence was 19.0% (95%CI: 16-22) in men and 20% (95%CI: 17-22) in women. In the final multivariable model, the probability for systolic IABPD ≥ 10 mmHg increased significantly with age (adjusted OR (aOR) = 1.10 (95%CI: 1.02-1.20) per 10-years), hypertension (aOR = 2.21; 95%CI: 1.68- 2.91) and diabetes (aOR = 1.69; 95%CI: 1.09-2.63). Conclusion: Almost one out of 5 native Africans have an IABPD ≥ 10 mmHg, with an increased risk with older age and presence of hypertension and diabetes. The clinical implication of our finding is in the importance of bilateral brachial blood pressure measurement in this setting.
NCOG-26. SOCIOECONOMIC FACTORS AFFECTING SURVIVORSHIP OF GLIOBLASTOMA PATIENTS IN THE PHILIPPINES: A RETROSPECTIVE COHORT STUDY
Authors: Manilyn Hong, Abdelsimar Omar, Kathleen Joy Khu
Journal: Neuro-Oncology (2021)

Abstract BACKGROUND Glioblastoma (GBM) is the most common malignant primary brain tumor in adults worldwide. However, data on the survivorship of glioblastoma for low-middle income countries is sparse. We studied the clinical features, treatment, and survivorship of surgically managed GBM patients at a tertiary referral center in the Philippines over a 5-year period. We determined whether socioeconomic factors such as income level, employment status, marital status and educational attainment affected survival. METHODS A retrospective cohort study within a 5-year period (2015 to 2019) of surgically managed GBM patients in a single center was conducted using chart review and telephone interview. RESULTS A total of 48 cases met the inclusion criteria. Mean age of the cohort was 41 years, with a male predilection (62%). Mean duration of symptoms was 2.8 months. Majority of the tumors were were &amp;gt;5 cm at the time surgery (90%), and involved more than one lobe (40%). Majority (73%) had preoperative KPS ≥70, and underwent subtotal resection (56%). Only 15% (n=7) had adjuvant chemoradiatherapy while another 23% (n=11) had radiotherapy alone. Median overall survival (OS) was 7.6 months (228 days). Most patients had rural residence (56%), low-income (83%), full time employment (79%), married status (73%) and secondary education (44%). Multi-variate analysis showed that only extent of resection (GTR p=0.0297 and STR p=0.0400) were associated with improved survival while widower status (p=0.0116) were significantly more at risk. CONCLUSION Many glioblastoma patients managed at our center in the Philippines presented at an advanced stage in their natural history, with larger tumors and more extensive distribution at time of presentation. After surgery, majority did not receive adjuvant treatment. As such, the median overall survival was less than that reported in published cohorts in developed countries. Extent of resection and marital status were significantly associated with survivorship.
Spontaneous Calvarial Infarction with Epidural Hematoma and Subgaleal Hemorrhage in a Teenager with Sickle Cell SS Disease and Glucose-6-Phosphate Dehydrogenase Deficiency
Authors: Jennifer Nestor, Danielle Sanders, Sukrita Mysore, Rafat Ahmed, Aubri Milano, Renata Ostrowicki, Odiraa Nwankwor, Thomas Presenza, Emily Scattergood
Journal: Blood (2021)