tbuckley/cabot-search huggingface dataset:
Abstract P091: Reasons For Uncontrolled Blood Pressure Among US Adults
Authors: Swati Sakhuja, Calvin Colvin, Oluwasegun Akinyelure, Shakia T Hardy, Paul Muntner
Journal: Circulation (2021)

Introduction: In October 2020, the US Surgeon General issued a Call to Action on hypertension control. We investigated the contribution of lack of awareness, not taking antihypertensive medication and an inadequate antihypertensive medication regimen to uncontrolled blood pressure (BP) among US adults. Methods: We analyzed data for 2,282 participants ≥18 years of age with uncontrolled BP from the 2015-2016 and 2017-2018 National Health and Nutrition Examination Surveys (NHANES). BP was measured three times by a trained physician following a standardized protocol. Uncontrolled BP was defined by systolic BP ≥140 mm Hg or diastolic BP ≥90 mm Hg. Being aware of having hypertension and antihypertensive medication use were defined by self-report. An inadequate antihypertensive medication regimen was defined as taking antihypertensive medication with uncontrolled BP. Data were weighted to represent the non-institutionalized US population. Results: Among US adults with uncontrolled BP, 34.8% were not aware they had hypertension, 13.8% were aware but not taking antihypertensive medication and 51.4% were aware but taking inadequate antihypertensive medication regimen. US adults 18-39 and 40-49 years of age were more likely to be unaware they had hypertension compared to their counterparts ≥70 years of age (multivariable-adjusted prevalence ratios [PR]: 1.62 [95% CI: 1.26-2.07] and 1.41 [95% CI: 1.02-1.95], respectively). Participants who had a healthcare visit in the past year (PR: 0.60 [95% CI: 0.47-0.77]) and who were obese (PR: 0.69 [95% CI: 0.56-0.85]), had diabetes (PR: 0.56 [95% CI: 0.42-0.76]), chronic kidney disease (PR: 0.59 [95% CI: 0.46-0.75]) and a history of cardiovascular disease (PR: 0.41 [95% CI: 0.27-0.61]) were less likely to be unaware they had hypertension. Among those who were aware they had hypertension, US adults who were 18-39 and 40-49 years of age as compared to those ≥70 years of age were more likely to be not taking antihypertensive medication versus taking inadequate antihypertensive medication regimen (multivariable-adjusted PR: 5.48 [95% CI: 3.17-9.48] and 5.14 [95% CI: 2.28-10.26], respectively). In contrast, non-Hispanic blacks and Hispanics as compared to non-Hispanic whites (PR: 0.71 [95% CI: 0.53-0.94] and 0.72 [95% CI: 0.54-0.96], respectively) and those without a usual place to receive healthcare (PR: 0.70 [95% CI 0.51-0.96]) and who had a healthcare visit in past year (PR: 0.47 [95% CI: 0.35-0.62]) were less likely to be not taking antihypertensive medication versus taking inadequate antihypertensive medication regimen. Conclusion: The majority of US adults with uncontrolled BP were either unaware they had hypertension or were taking an inadequate antihypertensive medication regimen. Interventions are needed to increase hypertension awareness and assess and titrate patients’ antihypertensive medication regimen.
The Mortality and Overall Survival Trends of Primary Liver Cancer in the United States
Authors: Yi-Te Lee, Jasmine J Wang, Michael Luu, Mazen Noureddin, Kambiz Kosari, Vatche G Agopian, Nicole E Rich, Shelly C Lu, Hsian-Rong Tseng, Nicholas N Nissen, Amit G Singal, Ju Dong Yang
Journal: JNCI Journal of the National Cancer Institute (2021)

Abstract Background Recent trends of hepatocellular carcinoma (HCC) mortality and outcome remain unknown in the United States. We investigated the recent trends of primary liver cancer (excluding intrahepatic cholangiocarcinoma) mortality and HCC stage, treatment, and overall survival (OS) in the United States. Methods The National Center for Health Statistics Database was analyzed to investigate the trend of primary liver cancer mortality. We analyzed the Surveillance, Epidemiology, and End Results 18 Database to assess the temporal trend of tumor size, stage, treatment, and OS of HCC. We investigated the association between HCC diagnosis year and OS using Cox regression analysis. All statistical tests were 2-sided. Results During 2000-2018, liver cancer mortality rates increased until 2013, plateaued during 2013-2016 (annual percent change = 0.1%/y, 95% confidence interval [CI] = −2.1%/y to 2.4%/y, P = .92), and started to decline during 2016-2018 (annual percent change = −1.5%/y, 95% CI = −3.2%/y to 0.2%/y, P = .08). However, mortality continues to increase in American Indian and Alaska Native, individuals aged 65 years or older, and in 33 states. There was a 0.61% (95% CI = 0.53% to 0.69%, P &amp;lt; .001) increase in localized stage HCC and a 0.86-mm (95% CI = −1.10 to −0.62 mm, P &amp;lt; .001) decrease in median tumor size per year. The 1-year OS rate increased from 36.3% (95% CI = 34.3% to 38.3%) to 58.1% (95% CI = 56.9% to 59.4%) during 2000-2015, and the 5-year OS rate almost doubled from 11.7% (95% CI = 10.4% to 13.1%) to 21.3% (95% CI = 20.2% to 22.4%) during 2000-2011. Diagnosis year (per year) (adjusted hazard ratio = 0.96, 95% CI = 0.96 to 0.97) was independently associated with OS in multivariable analysis. Conclusions Primary liver cancer mortality rates have started to decline in the United States with demographic and state-level variation. With an increasing detection of localized HCC, the OS of HCC has improved over the past decades.
HSCT corrects primary immunodeficiency and immune dysregulation in patients with POMP-related autoinflammatory disease
Authors: Caridad Martinez, Frédéric Ebstein, Sarah K. Nicholas, Marietta De Guzman, Lisa R. Forbes, Ottavia M. Delmonte, Marita Bosticardo, Riccardo Castagnoli, Robert Krance, Luigi D. Notarangelo, Elke Krüger, Jordan S. Orange, M. Cecilia Poli
Journal: Blood (2021)
Functional Outcomes Among Patients With Acute Ischemic Stroke After Mechanical Thrombectomy With or Without Intravenous Thrombolysis—Reply
Authors: Kazumi Kimura, Toshiaki Otsuka, Kentaro Suzuki
Journal: JAMA (2021)

In Reply Dr Mai and colleagues describe some concerns with the SKIP study,1 including the balance of baseline characteristics between the 2 groups, the sample size, and the noninferiority margin for the secondary outcome.
Legal reforms would allow GMC to tackle “shameful” discrimination of ethnic minority doctors
Authors: Clare Dyer
Journal: BMJ (2021)

The “shameful” discrimination experienced by too many doctors from ethnic minorities could be tackled under government proposals for radical reform of professional regulation, the chief executive of the General Medical Council has told health leaders.

Charlie Massey told a Westminster Health Forum conference that the reforms, which are open for consultation until 16 June, would give the GMC freedom to tackle discrimination and inequality within healthcare.1 The GMC and the other healthcare professional regulators would be given greater freedom over which cases to take forward, freeing up resources to focus on improvements in culture, training, and education.

Doctors from ethnic minorities are more likely than white doctors to be referred to the GMC by employers and more likely to be struck …
Expanded natural killer cells augment the antimyeloma effect of daratumumab, bortezomib, and dexamethasone in a mouse model
Authors: Jaya Lakshmi Thangaraj, Seo-Yeon Ahn, Sung-Hoon Jung, Manh-Cuong Vo, Tan-Huy Chu, Minh-Trang Thi Phan, Minsuk Kwon, Kyung-Hwa Lee, Mihee Kim, Ga-Young Song, Deok-Hwan Yang, Jae-Sook Ahn, Hyeoung-Joon Kim, Duck Cho, Je-Jung Lee
Journal: Cellular and Molecular Immunology (2021)
American Diabetes Association Framework for Glycemic Control in Older Adults: Implications for Risk of Hospitalization and Mortality
Authors: Mary R. Rooney, Olive Tang, Justin B. Echouffo Tcheugui, Pamela L. Lutsey, Morgan E. Grams, B. Gwen Windham, Elizabeth Selvin
Journal: Diabetes Care (2021)

OBJECTIVE The 2021 American Diabetes Association (ADA) guidelines recommend different A1C targets in older adults that are based on comorbid health status. We assessed risk of mortality and hospitalizations in older adults with diabetes across glycemic control (A1C &amp;lt;7%, 7 to &amp;lt;8%, ≥8%) and ADA-defined health status (healthy, complex/intermediate, very complex/poor) categories. RESEARCH DESIGN AND METHODS Prospective cohort analysis of older adults aged 66–90 years with diagnosed diabetes in the Atherosclerosis Risk in Communities (ARIC) study. RESULTS Of the 1,841 participants (56% women, 29% Black), 32% were classified as healthy, 42% as complex/intermediate, and 27% as very complex/poor health. Over a median 6-year follow-up, there were 409 (22%) deaths and 4,130 hospitalizations (median [25th–75th percentile] 1 per person [0–3]). In the very complex/poor category, individuals with A1C ≥8% (vs. &amp;lt;7%) had higher mortality risk (hazard ratio 1.76 [95% CI 1.15–2.71]), even after adjustment for glucose-lowering medication use. Within the very complex/poor health category, individuals with A1C ≥8% (vs. &amp;lt;7%) had more hospitalizations (incidence rate ratio [IRR] 1.41 [95% CI 1.03–1.94]). In the complex/intermediate group, individuals with A1C ≥8% (vs. &amp;lt;7%) had more hospitalizations, even with adjustment for glucose-lowering medication use (IRR 1.64 [1.21–2.24]). Results were similar, but imprecise, when the analysis was restricted to insulin or sulfonylurea users (n = 663). CONCLUSIONS There were substantial differences in mortality and hospitalizations across ADA health status categories, but older adults with A1C &amp;lt;7% were not at elevated risk, regardless of health status. Our results support the 2021 ADA guidelines and indicate that &amp;lt;7% is a reasonable treatment goal in some older adults with diabetes.
Abstract P162: Comorbid Asthma And Allergies Are Common In Children With Congenital Heart Disease And Related To Decreased Physical Functioning
Authors: Rochelle Medford, Carolyn Drews-Botsch, Michael Kramer, Matthew Oster, Bryan Williams, Jessica Knight
Journal: Circulation (2021)

Background: Congenital heart defects (CHD) are the most common birth defect and asthma and allergies are common conditions in childhood. The co-occurrence of these is not well understood but may be increased due to similar risk factors or immune dysregulation related to early life inflammation. This study aimed to compare the prevalence of asthma and allergies between children with CHD and their unaffected siblings and assess their impact on physical functioning in children with CHD. Methods: Parent-reported data was collected on allergy medications and asthma diagnosis, physical functioning (PedsQL physical health), and characteristics in children (age 12-17) with surgically treated CHD and an unaffected sibling (age 11-18). The McNemar test compared the comorbidities between siblings. Among children with CHD, logistic and linear regression were used to estimate the association of each comorbidity with child characteristics and physical functioning respectively. Models included CHD severity, SES, age, BMI, and sex. Results: Among 218 sibling pairs, the children with CHD had a higher, but not statistically significant, prevalence of asthma and allergies (Figure 1). In all 497 children with CHD, single ventricle CHD had a 2.5 times greater odds of allergies compared with non-critical (95%CI=1.0,6.0) with no difference in asthma. Asthma was associated with decreased physical functioning (8.7 point decrease vs no asthma, 95%CI=-14.5,-2.9). Conclusions: Children with CHD and their siblings had similar levels of allergies and asthma. However, as symptoms of these conditions may overlap, studies should further investigate a possible link with CHD, especially given the lower physical health in patients with CHD and asthma.
RNA Externalized by Neutrophil Extracellular Traps Promotes Inflammatory Pathways in Endothelial Cells
Authors: Luz P. Blanco, Xinghao Wang, Philip M. Carlucci, Jose Jiram Torres‐Ruiz, Jorge Romo‐Tena, Hong‐Wei Sun, Markus Hafner, Mariana J. Kaplan
Journal: Arthritis & Rheumatology (2021)

Neutrophil extracellular traps (NETs) are extracellular lattices composed of nucleic material bound to neutrophil granule proteins. NETs may play pathogenic roles in the development and severity of autoimmune diseases such as systemic lupus erythematosus (SLE), at least in part, through induction of type I interferon (IFN) responses via externalization of oxidized immunostimulatory DNA. A distinct subset of SLE proinflammatory neutrophils (low-density granulocytes [LDGs]) displays enhanced ability to form proinflammatory NETs that damage the vasculature. We undertook this study to assess whether NET-bound RNA can contribute to inflammatory responses in endothelial cells (ECs) and the pathways that mediate this effect.Expression of newly synthesized and total RNA was quantified in NETs from healthy controls and lupus patients. The ability of ECs to take up NET-bound RNA and downstream induction of type I IFN responses were quantified. RNAs present in NETs were sequenced and specific small RNAs were tested for induction of endothelial type I IFN pathways.NETs extruded RNA that was internalized by ECs, and this was enhanced when NET-bound nucleic acids were oxidized, particularly in lupus LDG-derived NETs. Internalization of NET-bound RNA by ECs was dependent on endosomal Toll-like receptors (TLRs) and the actin cytoskeleton and induced type I IFN-stimulated genes (ISGs). This ISG induction was dependent on NET-associated microRNA let-7b, a small RNA expressed at higher levels in LDG-derived NETs, which acted as a TLR-7 agonist.These findings highlight underappreciated roles for small RNAs externalized in NETs in the induction of proinflammatory responses in vascular cells, with implications for lupus vasculopathy.
Abstract 15375: Patients With Congenitally Corrected Transposition of the Great Arteries Following Anatomic Repair Are at Risk of Impaired Quality of Life
Authors: Tiffany R Lim, Kimberly Watkins, Rebecca R Hartog, Megan Wilde, Andrew Rodenbarger, Katherine Afton, Ray Lowery, Sunkyung Yu, Richard G Ohye, Adam L Dorfman, Caren S Goldberg
Journal: Circulation (2020)

Introduction: Children with complex congenital heart disease (CHD) are at increased risk for neurodevelopmental impairments and reduced quality of life (QOL). Patients (pts) with congenitally corrected transposition of the great arteries (ccTGA) often undergo anatomic repair to make the left ventricle the systemic ventricle, with the goal of long term cardiac benefits. Understanding long-term outcomes and QOL may inform preoperative counseling and treatment strategies for ccTGA. Methods: We measured QOL using PedsQL generic and cardiac modules for pts following anatomic repair of ccTGA with Senning/Arterial Switch or Senning/Rastelli operations. Impaired QOL by the PedsQL is defined by total scores &lt;65.4 for parent report and &lt;69.7 for pt report (possible score 0-100). Scores were compared to healthy controls and to pts with other forms of CHD, previously described in existing literature. Risk analysis for QOL impairment was performed using univariate logistic regression. Results: Of 88 eligible pts, 56 (64%) returned surveys (29% female, median age 11.8 years). Respondents were more likely to have pre-operative arrhythmias or pacemaker implantation compared to non-respondents. Mean total PedsQL score was 72 + 19 for pt report and 75 + 18 for parent report; 22 of 56 (39%) pts had impaired QOL scores, compared to 20% impaired scores in pts with any type of CHD, previously described. Mean physical functioning score was 72 + 22 for pt report and 76 + 21 for parent report. Mean psychosocial summary score was 73 + 18 and 75 + 18 for pt and parent report, respectively. Communication was the lowest scored subscale of the Cardiac module by pt (63 + 26) and parent (66 + 31) report. The treatment II subscale addressing medication compliance was the highest scored subscale with scores of 90 + 8 for pts and 91 + 15 for parent, respectively. Longer cardiopulmonary bypass time (p = 0.01), surgical or catheter-based reintervention following hospital discharge (p = 0.02) and heart failure symptoms (p = 0.04) were associated with impaired QOL. Conclusions: After anatomic repair of ccTGA, pts are at risk of impaired QOL compared to healthy controls and to pts with a broad range of CHD. Indicators of more complex surgical and post-operative courses were associated with impaired QOL.
Abstract 12605: Defining the Reference Range for Left Ventricular Strain by Echocardiography in Healthy Subjects: A Novel Meta-analysis Strategy
Authors: Tom Kai Ming Wang, Milind Y Desai, Patrick H Collier, Richard A Grimm, Brian Griffin, Zoran B Popovic
Journal: Circulation (2020)

Background: Left ventricular global longitudinal strain (LVGLS), circumferential strain (LVGCS) and radial strain (LVGRS) are established echocardiographic parameters of systolic function with wide clinical applicability and prognostic implications. Despite this, the reference ranges of left ventricular (LV) strain, particularly the lower limit of normal (LLN), are not well established. This meta-analysis aims to determine the mean and LLN of two- (2D) and three-dimensional (3D) LV strain in healthy subjects and factors that may influence strain measurements. Methods: We searched Pubmed, Embase and Cochrane databases until 30 November 2019 for studies reporting left ventricular (LV) global strain in at least 50 healthy subjects. We pooled the mean and LLN of 2D and 3D LV strain using random-effects models, and performed subgroup and meta-regression analysis for 2D-LVGLS. Results: Forty-four studies were eligible totaling 8747 subjects. The pooled means and LLNs (95% confidence intervals) were -20.0% (-20.6%, -19.5%) and -15.6% (-16.2%, -15.0%) respectively for 2D-LVGLS; -22.1% (-23.7%, -20.5%) and -15.7% (-17.3%, -14.1%) respectively for 2D-LVGCS; and 48.0% (43.8%, 52.1%) and 23.2% (20.9%, 25.5%) respectively for 2D-LVGRS; all listed in Table 1. Significant heterogeneity was observed for almost all pooled LV strain analyses. The only factors associated with significant differences in both pooled mean and LLN of 2D-LVGLS were systolic blood pressure and vendor software. Conclusion: Pooled means and LLNs of 2D- and 3D- LV global strain parameters in healthy subjects were reported. Based on the pooled LLNs and their confidence intervals, the thresholds for abnormal, borderline and normal LV strains can be defined. Systolic blood pressure and vendor software were the most important parameters influencing 2D-LVGLS mean and LLN. Our novel methodology can also be applied to the meta-analysis of other echocardiographic parameters to define reference ranges.
Converged Rab37/IL-6 trafficking and STAT3/PD-1 transcription axes elicit an immunosuppressive lung tumor microenvironment
Authors: I-Ying Kuo, You-En Yang, Pei-Shan Yang, Yu-Jou Tsai, Hong-Tai Tzeng, Hung-Chi Cheng, Wan-Ting Kuo, Wu-Chou Su, Chih-Peng Chang, Yi-Ching Wang
Journal: Theranostics (2021)

Background: Increased IL-6 level, M2 macrophages and PD-1+CD8+ T cells in tumor microenvironments (TME) have been identified to correlate with resistance to checkpoint blockade immunotherapy, yet the mechanism remains poorly understood. Rab small GTPase-mediated trafficking of cytokines is critical in immuno-modulation. We have previously reported dysregulation of Rab37 in lung cancer cells, whereas the roles of Rab37 in tumor-infiltrating immune cells and cancer immunotherapy are unclear. Methods: The tumor growth of the syngeneic mouse allograft in wild type or Rab37 knockout mice was analyzed. Imaging analyses and vesicle isolation were conducted to determine Rab37-mediated IL-6 secretion. STAT3 binding sites at PD-1 promoter in T cells were identified by chromatin immunoprecipitation assay. Multiplex fluorescence immunohistochemistry was performed to detect the protein level of Rab37, IL-6 and PD-1 and localization of the tumor-infiltrating immune cells in allografts from mice or tumor specimens from lung cancer patients. Results: We revealed that Rab37 regulates the secretion of IL-6 in a GTPase-dependent manner in macrophages to trigger M2 polarization. Macrophage-derived IL-6 promotes STAT3-dependent PD-1 mRNA expression in CD8+ T cells. Clinically, tumors with high stromal Rab37 and IL-6 expression coincide with tumor infiltrating M2-macrophages and PD1+CD8+ T cells that predicts poor prognosis in lung cancer patients. In addition, lung cancer patients with an increase in plasma IL-6 level are found to be associated with immunotherapeutic resistance. Importantly, combined blockade of IL-6 and CTLA-4 improves survival of tumor-bearing mice by reducing infiltration of PD1+CD8+ T cells and M2 macrophages in TME. Conclusions: Rab37/IL-6 trafficking pathway links with IL-6/STAT3/PD-1 transcription regulation to foster an immunosuppressive TME and combined IL-6/CTLA-4 blockade therapy exerts potent anti-tumor efficacy.
48P Abemaciclib combined with adjuvant endocrine therapy in patients from Asia with high risk early breast cancer: monarchE
Authors: Y-S. Yap, S-B. Kim, J.W.Y. Chiu, E. Lim, R. Broom, Z. Liu, Y. Sagara, T-Y. Chao, S. Sherwood, R.E. McNaughton, R.J. Wei, M. Toi
Journal: Annals of Oncology (2021)
心室性不整脈(VAs)の患者における活性化マッピングの空間分解能の有効性
Authors: Suzuki Masahito, Nitta Jyunnichi, Hayashi Yousuke, Sato Yoshikazu, Watanabe Keita, Inamura Yukihiro, Negi Ken, Hayashi Tatuya, Yamato Tunehiro, Sato Akira, Matumura Yutaka, Asakawa Kihiro, Goya Masahiko, Hirao Kenzo, Isobe Mituaki
Journal: Circulation (2015)
Abstract 15287: Evolocumab Inhibits the Acute Rise in Lipoprotein(a) in Patients With Non-ST Elevation Myocardial Infarction (NSTEMI)- Results From the EVACS Study
Authors: Michael Vavuranakis, Michael J Blaha, Steven R Jones, Thomas Schindler, Marlene S Williams, Jacqueline M Latina, Steven P Schulman, Gary Gerstenblith, Thorsten M Leucker
Journal: Circulation (2020)

Introduction: Elevated Lipoprotein(a) [Lp(a)] is associated with an increased risk of coronary heart disease (CHD). Although Lp(a) is mostly heritable, and controlled by the apo(a) gene, acute increases are described in small studies following acute coronary syndrome (ACS). PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibition modestly reduces Lp(a) in people with stable CHD but its effects during the early phase of an ACS are unknown. Hypothesis: Early administration of a PCSK9 inhibitor prevents a rise in Lp(a) following an ACS/NSTEMI. Methods: Participants from the EVACS trial (Evolocumab in Acute Coronary Syndrome; NCT03515304), all with a NSTEMI and a troponin-I of &gt; 5 ng/ml were randomized to placebo or to evolocumab. Serum Lp(a) was obtained at study entry prior to study drug and at 30 days. Normally distributed data were summarized using means and standard deviations and non-normally distributed data using medians and interquartile ranges. Results: Fifty-six participants were randomized to placebo (27) or to evolocumab (29). Mean age was 55±13 years, 41% were women and 27% were African American. The Scatterplots (Fig.1) demonstrate for those with a baseline Lp(a) of ≤75 nmol/L (the previously described optimal level) there was no increase in Lp(a) over the 30-day study period in either group. However, for those with a baseline Lp(a) of &gt;75 nmol/L there was a significant increase in the placebo group (Panel A), from a baseline of 176.5 nmol/L [131.5, 245.0] to 266 nmol/L [195.8, 302.5] at 30 days, p=0.02, but no increase in the evolocumab group (Panel B; baseline of 142 nmol/L [93, 177] to 137 nmol/L [96.8, 178.3], p=NS). The baseline values of those with Lp(a) of &gt;75 nmol/L did not differ between the groups; at 30 days, however, Lp(a) was higher in the placebo than in the evolocumab group (p=0.02; Panel C). Conclusions: Early administration of evolocumab prevents the acute increase in Lp(a) in those with a baseline Lp(a) of over 75 nmol/L following an ACS/NSTEMI.
Relation between Mechanical Restitution Property and Left Ventricular Systolic Function in Patients with Chronic Heart Failure
Authors: Hoyano Makoto, Kodama Makoto, Tanaka Komei, Mahmoud Ramadan, Mitsuma Wataru, Kashimura Takeshi, Itoh Masahiro, Hirono Satoru, Okura Yuji, Kato Kiminori, Hanawa Haruo, Aizawa Yoshifusa
Journal: Circulation (2006)