tbuckley/cabot-search huggingface dataset:
EPID-12. MITOCHONDRIAL DNA SEQUENCE VARIATION AND MENINGIOMA
Authors: Claudine Samanic, Jamie Teer, Zachary Thompson, Jordan Creed, Brooke Fridley, L Burt Nabors, Sion L Williams, Kathleen Egan
Journal: Neuro-Oncology (2021)

Abstract Meningiomas are the most common primary central nervous system tumors. Risk factors include female sex, African American race, a higher body mass index, and exposure to ionizing radiation. Genome-wide association studies have identified two risk loci for meningioma in the nuclear genome (rs12770228 and rs2686876). Whereas mitochondrial DNA (mtDNA) sequence variants and haplogroups have been linked with certain cancers, research on meningioma is lacking. We examined the association of 42 common (minor allele frequency ≥ 5%) germline mtDNA variants, haplogroups, and genes with meningioma risk in 1,080 controls and 478 cases from a case-control study conducted at medical centers in the southeastern US. Participant DNA samples were genotyped using the UK Biobank array that included a set of common and rare mtDNA variants. Risk associations were examined separately for meningioma overall, WHO grade 1 (n=409) and WHO grade 2/3 (n=69) meningiomas. Overall, meningioma risk was significantly higher among women (OR=2.86; 95% CI:2.21-3.71) compared to men, higher among African Americans (OR=2.37, 95% CI:1.41-3.99) compared to Caucasians, and higher among those who were overweight (OR=1.48; 95% CI:1.11-1.98) or obese (OR= 1.73; 95% CI:1.26-2.38) compared to those of normal weight. The variant m.16362T &amp;gt;C (rs62581341) in the mitochondrial control region was positively associated with grade 2/3 meningiomas (OR=2.33; 95% CI: 1.14-4.79), but not with grade 1 tumors (OR=0.99; 95% CI:0.64-1.53). Haplogroup L, a marker for African ancestry, was identified among 3.6% of controls and 8.6% of cases and was associated with meningioma risk overall (OR=2.56; 95% CI:1.52-4.30). When stratifying by self-reported race, the association between haplogroup L and meningioma was only apparent among the small number of self-reported Caucasians with this haplogroup (OR=6.68; 95% CI=1.66-26.91) when compared to non-L haplogroups, combined. No other common mtDNA variant (minor allele &amp;gt;5%), haplogroup, or gene was associated with meningioma risk. These findings merit further study.
Abstract 10970: Added Predictive Value of Right Ventricular Ejection Fraction Compared with Conventional Echocardiographic Measurements in Patients Who Underwent Diverse Cardiovascular Procedures
Authors: Alexandra Fabian, Máté Tolvaj, Marton Tokodi, Balint K Lakatos, Adrienn Ujvari, Fjolla Zhubi Bakija, Zsuzsanna Ladanyi, Zsofia Tarcza, Béla Merkely, Attila Kovacs
Journal: Circulation (2021)

Introduction: Right ventricular (RV) ejection fraction (EF) assessed by 3D echocardiography is a powerful measure to detect RV dysfunction. However, its prognostic value in routine clinical practice has been scarcely explored. Accordingly, we aimed at investigating whether RVEF is associated with 2-year all-cause mortality in patients who underwent diverse cardiovascular procedures and to test whether RVEF can overcome conventional echocardiographic parameters in terms of outcome prediction. Methods: One hundred and seventy-four patients were retrospectively identified who underwent clinically indicated transthoracic echocardiography comprising 3D acquisitions. The patient population consisted of heart failure with reduced ejection fraction patients (44%), heart transplanted patients (16%), and severe valvular heart disease patients (39%). Beyond conventional echocardiographic measurements, RVEF was quantified by 3D echocardiography. The primary endpoint of our study was all-cause mortality at two years. Results: Twenty-four patients (14%) met the primary endpoint. Patients with adverse outcomes had significantly lower RVEF (alive vs. dead; 48±9 vs. 42±9%, p&lt;0.01). However, tricuspid annular plane systolic excursion (21±7 vs. 18±4mm), and RV systolic pressure (36±15 vs. 39±15mmHg) were similar. By Cox analysis, RVEF was found to be associated with adverse outcomes (HR [95% CI]: 0.945 [0.908 - 0.984], p&lt;0.01). By receiver-operator characteristic analysis, RVEF exhibited the highest AUC value compared with the other RV functional measures (0.679; 95% CI: 0.566 - 0.791). Conclusions: Conventional echocardiographic measurements may be inadequate to support a granular risk stratification in patients who underwent different cardiac procedures. RVEF may be a robust clinical parameter, which is significantly associated with adverse outcomes.
Maintenance Therapy in Patients with <i>FLT3</i>-ITD-Mutation-Positive Acute Myeloid Leukemia after Allogeneic Hematopoietic Cell Transplantation: Real-World Survival
Authors: Hongbo Yang, Yan Song, James D. Griffin, Manasee V. Shah, Jonathan Freimark, Andrew Chilelli
Journal: Blood (2021)
Abstract 10751: Pericardial Injection of Micronized Matrix Biomaterial Improves Post-Infarct Cardiac Function and Modulates Fibroblast Activity to Enhance Repair
Authors: Vishnu Vasanthan, darrell belke, Guoqi Teng, Ali Fatehi Hassanabad, Jameson Dundas, Jeannine Turnbull, Justin Deniset, Paul W Fedak
Journal: Circulation (2021)

Introduction: Injection of micronized biomaterials into the pericardial space leverages bioinductive properties to enhance post-infarct cardiac repair. This less invasive, potentially bedside, approach enables early intervention. Micronized porcine small intestinal submucosal extracellular matrix (SIS-ECM) contains fibroblast growth factor 2 (FGF2) which reduce fibrosis and increase vasculogenesis. Hypothesis: Pericardial delivery of micronized SIS-ECM improves post-infarct cardiac function. It promotes a proangiogenic and antifibrotic fibroblast phenotype. Methods: Mice received coronary ligation (infarct) through an undisrupted pericardium followed by pericardial delivery of micronized SIS-ECM or saline control. Pressure-volume loops were at 28 days. Myocardial isolectin stain assessed small vessel density on confocal microscopy. Mouse 3T3 cell line fibroblasts in 3D collagen matrices were exposed to biomaterial-conditioned media or media control. Multiplex analyzed paracrine activity. Collagen gel contraction and MMP2 production assessed profibrotic phenotype. FGF2 inhibitor elucidated mechanism. Results: Mice receiving micronized SIS-ECM had lower ventricular stiffness (0.23±0.03 vs 0.39±0.05 mmHg/uL; p=0.01), higher ejection fraction (34.7±2.5 vs 26.9±2.8%; p&lt;0.05) and higher stroke work (1510±138 vs 1066±152 μL/mmHg; p=0.04). The SIS-ECM group had higher normalized border zone isolectin mean fluorescence (0.82±0.04 vs 0.58±0.06; p=0.01). Micronized SIS-ECM attenuated collagen gel contraction (26±6 vs 56±5%; p=0.01) and MMP2 release (66±2 vs 83±3 ng/mL; p&lt;0.01). Micronized SIS-ECM increased fibroblast VEGF production (904±79 vs 628±25; pg/mL). FGF2 inhibitor negated biomaterial effects, increasing gel contraction (27.3±5.3 vs 11.0±0.5%; p=0.04; inhibitor vs no inhibitor) and MMP-2 release (141±8 vs 100±6 ng/mL; p=0.02). Conclusions: Pericardial injection of micronized SIS-ECM attenuates profibrotic fibroblast activity, increases release of angiogenic VEGF protein, increases vasculogenesis on isolectin staining, and preserves post-infarct cardiac function. This less invasive strategy facilitates early intervention to attenuate maladaptive post-infarct structural remodeling.
The Short-Term Efficacy and Safety of Brentuximab Vedotin Plus Cyclophosphamide, Epirubicin and Prednisone Acetate in Peripheral T Cell Lymphomas: A Real-World, Retrospective Case Series from China
Authors: Wei Guo, Xiaomeng Feng, Yinping Wang, Jia Li, Yangzhi Zhao, Limei Qu, Xu Yan, Junna Li, Qiang Guo, Ken H. Young, Ou Bai
Journal: Blood (2021)
Abstract 9901: Double Cardiac Threat of Concomitant Spontaneouscoronary Artery Dissection and Takotsubo Cardiomyopathy
Authors: Tatiana Echeverry, Christian Daniel Barrera Maldonado, Robert Fishberg
Journal: Circulation (2021)

Spontaneous Coronary Artery Dissection is an important cause of ACS in females with few atherosclerosis risk factors. SCAD accounts for 25% of ACS cases in women&lt;50 years of age. Takotsubo Cardiomyopathy (TTC) is also a cause of ACS in this group with similar presentation to SCAD. The coexistence of SCAD and TTC has been reported in the literature, emphasizing the importance of an accurate diagnosis. The following case highlights the coexistence of SCAD and TTC and the importance of updated guidelines to identify concomitant TTC and SCAD. Multiparous 41-year-old female, eight days after delivery, was found in cardiac arrest. Patient was intubated, CPR was initiated and after delivery of three shocks, ROSC was achieved. Upon arrival to the hospital, patient underwent TTM. Initial EKG showed no acute ischemic changes and troponin of 27. Patient underwent ECHO EF 40-45% with antero-apical and infero-apical akinesia. On day three, EKG showed ST elevations in leads V2-V6 and following day underwent cardiac catheterization showing an area of dissection in the distal LAD. SCAD and TTC are non-atherosclerotic coronary artery diseases that account for ACS among females. In women &lt;50 years of age, SCAD accounts for 25% of ACS cases. While TTC accounts for 2% of all ACS cases. The diagnosis of SCAD versus TTC could be difficult since both conditions present in similar ways. It is important to recognize that SCAD and TTC can coexist since accurate diagnosis changes treatment. TTC should improve with subsequent echocardiograms. Patients with SCAD should be started on DAPT and identify risk factors such as FMD or aneurysm in other vascular beds. In our patient, the distal LAD is dissected but appears to be a small vessel leading to the antero-apex. However, the distal LAD does not appear to supply the infero-apical area, and the infero-apical hypokinesis is best explained as a component of TTC. Currently, TTC is diagnosed by echo showing transient left ventricular dysfunction and based on clinical presentation, as described by InterTAK diagnostic criteria. However, the InterTAK criteria do not take into account the possible coexistence of TTC and SCAD. Cardiac catheterization should be strongly considered in all cases of TTC to clarify the diagnosis of concomitant TTC and SCAD.
EXTH-58. THERAPEUTIC HDAC INHIBITION IN HYPERMUTANT DIFFUSE INTRINSIC PONTINE GLIOMA
Authors: Alyssa Noll, Matt Biery, Carrie Myers, Danyelle Paine, Ye Zheng, Emily Girard, Conrad Winter, Shelli Morris, Mi-Youn Brusniak, Raphael Gottardo, Andrew Mhyre, Jessica Foster, Matthew Dun, Muhammed Murtaza, Michael Berens, James Olson, Nicholas Vitanza
Journal: Neuro-Oncology (2021)

Abstract Diffuse intrinsic pontine glioma (DIPG) continues to carry a dismal prognosis despite a growing understanding of its epigenetic regulation. While generally reclassified as diffuse midline glioma, H3 K27M-mutant (DMG), a subgroup of DIPGs do not harbor the classic histone mutation, with a further subset exhibiting a hypermutant phenotype. To evaluate whether hypermutant DIPG shares transcriptional vulnerabilities with H3K27M-mutant DMG, we screened a biopsy-derived treatment-naive PMS2 mutant DIPG model (PBT-24FH) for sensitivity to a panel of HDAC inhibitors (HDACi). In vitro evaluation of cell viability revealed the low nanomolar IC50 of quisinostat (50nM) and romidepsin (2nM). Dose-dependent increases in H3 acetylation and c-PARP were confirmed by western blot. Despite romidepsin’s superior potency in vitro, quisinostat demonstrated greater efficacy in an in vivo PBT-24FH flank study. 42 days following drug initiation, quisinostat-treated mice displayed dramatic tumor regression (mean volume= 33mm3, n= 7) compared to mice treated with romidepsin (mean volume= 669mm3, n= 7)(p= 0.005), or vehicle (mean volume= 990mm3, n= 6)(p&amp;lt; 0.001). Immunohistochemistry of quisinostat-treated tumors revealed few residual tumor cells displaying a low proliferative index. To evaluate cross-resistance, romidepsin-treated mice (mean volume= 1158mm3, n= 2) were switched to quisinostat treatment and displayed swift tumor regression (mean volume after 25 days of quisinostat= 419mm3), emphasizing quisinostat’s in vivo cytotoxic effect against both large tumors and tumors previously treated by another HDACi. To evaluate quisinostat’s effect on other hypermutant tumors, we tested HCT-116, a colon cancer cell line bearing a biallelic MLH1 deletion and observed similar cytotoxicity. We also aim to repeat these studies utilizing additional pediatric hypermutant high grade glioma models. Transcriptomic and proteomic investigations are underway to identify the mechanism of action underlying quisinostat-induced cytotoxicity. Ultimately, we are the first to demonstrate in vivo efficacy of the HDACi quisinostat against hypermutant DIPG, supporting further investigation and clinical advancement.
Abstract 10778: Long-Term Functional Outcomes in Older Adults After Hospitalization for Extracranial Hemorrhage
Authors: Anna L Parks, Sun Y Jeon, John J Boscardin, Michael A Steinman, Alexander K Smith, Margaret C Fang, kenneth E covinsky, Sachin J Shah
Journal: Circulation (2021)

Introduction: Antiplatelet and anticoagulant medications often used to manage cardiovascular disease increase the risk of extracranial hemorrhage (ECH), such as gastrointestinal bleeding. There are few long-term data on the loss of function following ECH. This study’s goal was to measure the acute and persistent loss of independence in activities of daily living (ADLs) after ECH hospitalization. Methods: We used data from 1995-2015 from the Health and Retirement Study, a longitudinal, nationally representative survey of older Americans. We included subjects over age 65 who consented to Medicare linkage. We examined the association of ECH hospitalization with ability to perform all ADLs independently (walk across a room, dress, bathe, eat, toilet, get out of bed). To compare rates of ADL independence over time between those with ECH and a control group without ECH, we fit a logistic regression model that included an interaction term between ECH hospitalization and time and adjusted for comorbidities and sociodemographics. Results: In a cohort of 8950 with an average follow-up time of 7.3 years (65,335 person-years), 882 (10%) participants were hospitalized for ECH. Mean age was 78, and 59% were women. In the control group without ECH, the baseline rate of ADL independence declined by an average of 3.1% per year (average marginal effect [AME], 95% CI -3.1% to -3.3%). Assuming hospitalization for ECH at 5.2 years, the median time to ECH in this cohort, ECH was associated with an immediate decrease in ADL independence from 68% to 53% (AME -15%, 95% CI -11% to -18%). Following ECH, the average annual baseline rate of function loss did not change. Conclusions: In this nationally representative cohort, ECH hospitalization was associated with an immediate and pronounced decline in function that was equivalent to accelerating ADL disability by 5 years. After ECH, ADL independence continued to decline and did not recover to pre-ECH levels of independence over time.
104P Exploring the real-world impact of COVID-19 on first line (1L) treatment and management of EGFR-wild type (EGFR-WT) and ALK-wild type (ALK-WT) metastatic non-small cell lung cancer (mNSCLC) across Europe
Authors: H. Bailey, A. Lee, L. Eccles, Y. Yuan, M. Last, H. Burlison, C. Forshaw, N. Varol
Journal: Annals of Oncology (2021)
Association of Chronic Lower Respiratory Disease With County Health Disparities in New York State
Authors: Yu-Che Lee, Ko-Yun Chang, Sanjay Sethi
Journal: JAMA Network Open (2021)

<h3>Importance</h3> Chronic lower respiratory disease (CLRD) is the fourth leading cause of death in the United States, which imposes a considerable burden on individuals, families, and societies. The association between county-level health disparity and CLRD outcomes in New York state needs investigation. <h3>Objective</h3> To evaluate the associations of CLRD outcomes with county-level health disparities in New York state. <h3>Design, Setting, and Participants</h3> In this cross-sectional study, CLRD age-adjusted hospitalization for 2016 and mortality rates from 2014 to 2016 were obtained from the New York state Community Health Indicator Reports provided by the New York state Department of Health. County Health Rankings were used to evaluate various health factors to provide a summary<i>z</i>score for each county representing the county health status and how that county ranks in the state. Data analysis was performed from November 2020 to March 2021. <h3>Main Outcomes and Measures</h3> The main outcomes were age-adjusted hospitalization and mortality rates for CLRD. The<i>z</i>score was calculated from the County Health Rankings, which includes subindicators of health behaviors, clinical care, social and economic factors, and physical environment. Pearson<i>r</i>and linear regression models were estimated. <h3>Results</h3> During the study, 60 335 discharges were documented as CLRD hospitalizations in 2016 and 20 612 people died from CLRD from 2014 to 2016 in New York state. After adjusting for age, the CLRD hospitalization rate was 27.6 per 10 000 population, and the mortality rate was 28.9 per 100 000 population. Among 62 counties, Bronx had the highest hospitalization rate (64.7 per 10 000 population) whereas Hamilton had the lowest hospitalization rate (6.6 per 10 000 population). Mortality rates ranged from 17.4 per 100 000 population in Kings to 62.9 per 100 000 population in Allegany. County Health Rankings indicated Nassau had the lowest<i>z</i>score (the healthiest), at −1.17, but Bronx had the highest<i>z</i>score (the least healthy), at 1.43, for overall health factors in 2018. An increase of 1 point in social and economic factors<i>z</i>score was associated with an increase of 17.6 hospitalizations per 10 000 population (β = 17.61 [95% CI, 10.36 to 24.87];<i>P</i> &lt; .001). A 1-point increase in health behaviors<i>z</i>score was associated with an increase of 41.4 deaths per 100 000 population (β = 41.42 [95% CI, 29.88 to 52.97];<i>P</i> &lt; .001). <h3>Conclusions and Relevance</h3> In this cross-sectional study, CLRD outcomes were significantly associated with county-level health disparities in New York state. These findings suggest that public health interventions and resources aimed at improving CLRD outcomes should be tailored and prioritized in health disadvantaged areas.
Chinese Consensus Report on Family-Based<i>Helicobacter pylori</i>Infection Control and Management (2021 Edition)
Authors: Song-Ze Ding, Yi-Qi Du, Hong Lu, Wei-Hong Wang, Hong Cheng, Shi-Yao Chen, Min-Hu Chen, Wei-Chang Chen, Ye Chen, Jing-Yuan Fang, Heng-Jun Gao, Ming-Zhou Guo, Ying Han, Xiao-Hua Hou, Fu-Lian Hu, Bo Jiang, Hai-Xing Jiang, Chun-Hui Lan, Jing-Nan Li, Yan Li, Yan-Qing Li, Jie Liu, You-Ming LI, Bin Lyu, You-Yong Lu, Ying-Lei Miao, Yong-Zhan Nie, Jia-Ming Qian, Jian-Qiu Sheng, Cheng-Wei Tang, Fen Wang, Hua-Hong Wang, Jiang-Bin Wang, Jing-Tong Wang, Jun-Ping Wang, Xue-Hong Wang, Kai-Chun Wu, Xing-Zhou Xia, Wei-Fen Xie, Yong Xie, Jian-Ming Xu, Chang-Qing Yang, Gui-Bin Yang, Yuan Yuan, Zhi-Rong Zeng, Bing-Yong Zhang, Gui-Ying Zhang, Guo-Xin Zhang, Jian-Zhong Zhang, Zhen-Yu Zhang, Peng-Yuan Zheng, Yin Zhu, Xiu-Li Zuo, Li-Ya Zhou, Nong-Hua Lyu, Yun-Sheng Yang, Zhao-Shen Li
Journal: Gut (2021)

Helicobacter pylori infection is mostly a family-based infectious disease. To facilitate its prevention and management, a national consensus meeting was held to review current evidence and propose strategies for population-wide and family-based H. pylori infection control and management to reduce the related disease burden.Fifty-seven experts from 41 major universities and institutions in 20 provinces/regions of mainland China were invited to review evidence and modify statements using Delphi process and grading of recommendations assessment, development and evaluation system. The consensus level was defined as ≥80% for agreement on the proposed statements.Experts discussed and modified the original 23 statements on family-based H. pylori infection transmission, control and management, and reached consensus on 16 statements. The final report consists of three parts: (1) H. pylori infection and transmission among family members, (2) prevention and management of H. pylori infection in children and elderly people within households, and (3) strategies for prevention and management of H. pylori infection for family members. In addition to the 'test-and-treat' and 'screen-and-treat' strategies, this consensus also introduced a novel third 'family-based H. pylori infection control and management' strategy to prevent its intrafamilial transmission and development of related diseases.H. pylori is transmissible from person to person, and among family members. A family-based H. pylori prevention and eradication strategy would be a suitable approach to prevent its intra-familial transmission and related diseases. The notion and practice would be beneficial not only for Chinese residents but also valuable as a reference for other highly infected areas.
Nitric oxide facilitates the targeting Kupffer cells of a nano-antioxidant for the treatment of NASH
Authors: Hitoshi Maeda, Yu Ishima, Junji Saruwatari, Yuki Mizuta, Yuki Minayoshi, Shota Ichimizu, Hiroki Yanagisawa, Taisei Nagasaki, Kengo Yasuda, Shun Oshiro, Manabu Taura, Matthew J. McConnell, Kentaro Oniki, Kayoko Sonoda, Tomohiko Wakayama, Manabu Kinoshita, Tsuyoshi Shuto, Hirofumi Kai, Motohiko Tanaka, Yutaka Sasaki, Yasuko Iwakiri, Masaki Otagiri, Hiroshi Watanabe, Toru Maruyama
Journal: Journal of Controlled Release (2021)
Cholesteryl ester transfer protein inhibitors: from high-density lipoprotein cholesterol to low-density lipoprotein cholesterol lowering agents?
Authors: Nick S Nurmohamed, Marc Ditmarsch, John J P Kastelein
Journal: Cardiovascular Research (2021)

Cholesteryl ester transfer protein (CETP) is a liver-synthesized glycoprotein whose main functions are facilitating transfer of both cholesteryl esters from high-density lipoprotein (HDL) particles to apolipoprotein B (apoB)-containing particles as well as transfer of triglycerides from apoB-containing particles to HDL particles. Novel crystallographic data have shown that CETP exchanges lipids in the circulation by a dual molecular mechanism. Recently, it has been suggested that the atherosclerotic cardiovascular disease (ASCVD) benefit from CETP inhibition is the consequence of the achieved low-density lipoprotein cholesterol (LDL-C) and apoB reduction, rather than through the HDL cholesterol (HDL-C) increase. The use of CETP inhibitors is supported by genetic evidence from Mendelian randomization studies, showing that LDL-C lowering by CETP gene variants achieves equal ASCVD risk reduction as LDL-C lowering through gene proxies for statins, ezetimibe, and proprotein convertase subtilisin-kexin Type 9 inhibitors. Although first-generation CETP inhibitors (torcetrapib, dalcetrapib) were mainly raising HDL-C or had off-target effects, next generation CETP inhibitors (anacetrapib, evacetrapib) were also effective in reducing LDL-C and apoB and have been proven safe. Anacetrapib was the first CETP inhibitor to be proven effective in reducing ASCVD risk. In addition, CETP inhibitors have been shown to lower the risk of new-onset diabetes, improve glucose tolerance, and insulin sensitivity. The newest-generation CETP inhibitor obicetrapib, specifically designed to lower LDL-C and apoB, has achieved significant reductions of LDL-C up to 45%. Obicetrapib, about to enter phase III development, could become the first CETP inhibitor as add-on therapy for patients not reaching their guideline LDL-C targets.
Keith Douglas John Vowles
Authors: Rob Vowles
Journal: BMJ (2021)

My father, Keith Douglas John Vowles, has died at the Royal Devon and Exeter Hospital (fittingly) after a brief struggle with pneumonia at the age of 98. Amazingly he had caught and survived covid twice during his last year.

Educated at Bristol Grammar School, he qualified from Bristol University. After house posts in Bristol, Worcester, and York he served in the Royal Army Medical Corps in Cyrenaica (now Libya) (BMH Benghazi) as …