tbuckley/cabot-search huggingface dataset:
Abstract 11779: E-cigarette Nicotine Vapor Increases Aortic Stiffness in Mice
Authors: Pireyatharsheny Mulorz, Joscha U Mulorz, YaeHyun Rhee, Lasse Bach Steffensen, Hans Beck, Markus Wagenhaeuser, Joshua Spin, Philip S Tsao
Journal: Circulation (2021)

Introduction: Arterial stiffness is increased by smoking and is a risk factor for various cardiovascular diseases. In recent years electronic cigarettes (e-cigs) have gained worldwide popularity as potentially “healthier” substitutes for conventional smoking, especially among young adults and teenagers. These devices provide nicotine at levels equal to or greater than those from conventional cigarettes. To date, little is known about the effects of e-cigs on vasculature. We investigated whether inhaled nicotine through e-cig vapor leads to enhanced aortic stiffening through extracellular matrix remodeling in both young and adult mice. Hypothesis: Inhalation of nicotine vapor augments aortic stiffening process when compared to e-juice only or room air. Methods: Young (6-week-old) and adult (14-week-old) male C57BL/6J mice were exposed to unflavored e-cig vapor with or without nicotine (24 mg/ml) at 9 puffs/min for 1 hour/day for 21 consecutive days, or room air. In vivo aortic stiffness was assessed by measurement of pulse wave velocity. At the end of the time-course the aorta was explanted for segmental pressure myographic measurements. Blood pressure and pulse rate were tracked throughout the experiment utilizing a non-invasive tail-cuff-system. A subset of aortic tissue was also subjected to exploratory transcriptional profiling. Results: Exposure to e-cig vapor containing nicotine significantly augmented aortic stiffness when compared to room air or e-juice only exposed mice. This was apparent in both pulse wave velocity measurements and pressure myography. Observed effects were more pronounced in young mice when compared to adult animals, and occurred in both the thoracic and abdominal aortic segments. Expression array data identified changes between the groups. There were no significant differences between room air-exposed mice and mice exposed to e-juice without nicotine. Conclusion: Inhaled e-cig nicotine significantly increased murine aortic stiffness in both aortic segments after three weeks of daily exposure, especially in younger mice. Further clinical investigations into the direct effects of nicotine e-cigarettes on human vasculature, especially in young people, are warranted to contextualize these results.
Resident and migratory adipose immune cells control systemic metabolism and thermogenesis
Authors: Kevin Man, Axel Kallies, Ajithkumar Vasanthakumar
Journal: Cellular and Molecular Immunology (2021)

Abstract Glucose is a vital source of energy for all mammals. The balance between glucose uptake, metabolism and storage determines the energy status of an individual, and perturbations in this balance can lead to metabolic diseases. The maintenance of organismal glucose metabolism is a complex process that involves multiple tissues, including adipose tissue, which is an endocrine and energy storage organ that is critical for the regulation of systemic metabolism. Adipose tissue consists of an array of different cell types, including specialized adipocytes and stromal and endothelial cells. In addition, adipose tissue harbors a wide range of immune cells that play vital roles in adipose tissue homeostasis and function. These cells contribute to the regulation of systemic metabolism by modulating the inflammatory tone of adipose tissue, which is directly linked to insulin sensitivity and signaling. Furthermore, these cells affect the control of thermogenesis. While lean adipose tissue is rich in type 2 and anti-inflammatory cytokines such as IL-10, obesity tips the balance in favor of a proinflammatory milieu, leading to the development of insulin resistance and the dysregulation of systemic metabolism. Notably, anti-inflammatory immune cells, including regulatory T cells and innate lymphocytes, protect against insulin resistance and have the characteristics of tissue-resident cells, while proinflammatory immune cells are recruited from the circulation to obese adipose tissue. Here, we review the key findings that have shaped our understanding of how immune cells regulate adipose tissue homeostasis to control organismal metabolism.
BIOM-29. ASSOCIATION OF PLASMA microRNA-21 EXPRESSION WITH KARNOFSKY PERFORMANCE SCALE SCORES IN GLIOMA PATIENTS
Authors: Rusdy Malueka, Ery Dwianingsih, Maria Alethea, Adiguno Wicaksono, Kusumo Dananjoyo, Ahmad Asmedi, Rachmat Hartanto
Journal: Neuro-Oncology (2021)

Abstract Gliomas are one of the most common primary brain tumors. MicroRNA-21 (miRNA-21) has been shown in previous studies to be associated with prognosis in glioma patients. However, similar studies in the Asian population, particularly in Indonesia, are very limited. This study aimed to find the association of plasma miRNA-21 expression with functional status measured by Karnofsky Performance Scale (KPS) in Indonesian glioma patients. The patients were enrolled from a neuro-oncology referral center in Yogyakarta, Indonesia. MiRNA-21 expression from plasma was measured by real-time quantitative PCR. Clinical data were obtained from medical records. KPS scores were classified as low (&amp;lt; 70) and high (&amp;gt; 70). In total, 50 patients were included in this study. Most patients were diagnosed with WHO grade IV gliomas (30.4%), followed by grade II (30.4%), grade III (21.4%), and grade I (5.4%). Most patients (64%) have low KPS scores (&amp;lt; 70). Patients in the low KPS scores group have significantly higher miRNA-21 expression compared to patients in the high KPS scores group (2-∆CT 4.26 vs. 0.68, p=0.002). In conclusion, higher expression of plasma miRNA-21 is associated with worse functional status in glioma patients as measured by KPS.
Abstract 11522: The Risk of Cardiovascular Diseases in Women with Recurrent Pregnancy Loss: A Systematic Review and Meta-Analysis
Authors: Bo Peng, Hong Yu Wang, Decontee Kaye, Yeonjoo Cho, Delaney Goulet, Matthew Hansen, Dennis Goulet
Journal: Circulation (2021)

Introduction: Recurrent pregnancy loss (RPL) is defined as two or more ultrasound confirmed pregnancy losses or three or more pregnancy losses at any location. Evidence suggests that women with a history of RPL have an increased risk of coronary heart disease. However, the association between cardiovascular diseases (CVD) and RPL remains unclear. We aim to conduct a systematic review and meta-analysis to investigate whether RPL is a risk factor for CVD. Methods: Population-based studies on MEDLINE, CINAHL, Web of Science, and Embase that investigated the risk of CVD in women with or without a history of RPL were included. The incidences of CVD events and its composite endpoints myocardial infarction/coronary heart diseases (MI/CHD), stroke/cerebrovascular diseases (stroke/CeVD), circulatory system diseases (CSD) were extracted and presented with odds ratio (OR) with 95% confidence interval (CI). Heterogeneity was analyzed with I 2 . Results: A total of 809 articles were retrieved and 6 studies were included. The incidences of CVD events was significantly increased (OR=1.49, 95% CI 1.11 to 1.99, P=0.008, I 2 =96%) in 13176 women with RPL (≥2 pregnancy losses) compare to 403278 controls; a borderline increase of MI/CHD risk was also found (OR=1.45, 95% CI 1.00 to 2.08, P=0.05, I 2 =78%), whereas no significant differences of stroke/CeVD (OR=1.25, 95% CI 0.79 to 1.98, P=0.35, I 2 =73%) and CSD risks (OR=1.17, 95% CI 0.83 to 1.67, P=0.05, I 2 =93%) were observed. In 1594 women with three or more pregnancy losses, an increased incidence of CVD events was found compared to 311385 women without (OR=1.59, 95% CI 1.04 to 2.40, P=0.03, I 2 =71%). The risks of MI/CHD (OR=3.03, 95% CI 1.45 to 6.35, P=0.003, I 2 =78%) and stroke/CeVD (OR=1.63, 95% CI 1.38 to 1.93, P&lt;0.00001, I 2 =0%) were significantly increased in these women but not CSD (OR=1.27, 95% CI 0.92 to 1.76, P=0.13, I 2 =57%). Conclusion: Our study suggested an association between RPL and increased risks of CVD and MI/CHD. The risks of stroke/CeVD may be elevated in women with three or more pregnancy losses. Our work provides a better understanding of the sex-specific risk factors of CVD. Further research may help to identify the causal link between RPL and CVD and determine the need for early screening and intervention in women at risk.
IMMU-03. IMMUNE CHECKPOINT INHIBITORS IN SMALL CELL LUNG CANCER PATIENTS DEVELOPING BRAIN METASTASES
Authors: Charissa Jessurun, Ishaan Tewarie, Alexander Hulsbergen, Marike Broekman, Timothy Smith, John phillips
Journal: Neuro-Oncology (2021)

Abstract INTRODUCTION Small cell lung cancer (SCLC) is known for rapid growth, and about 40-50% of SCLC patients will develop brain metastases (BM). The addition of immune checkpoint inhibitors (ICI) to the standard chemotherapy, which is the current backbone of first-line therapy, has resulted in more prolonged survival than chemotherapy alone in SCLC patients. PURPOSE This study aimed to assess the effect of ICI before BM development in SCLC patients on time to BM development and survival. METHODS A single-institutional retrospective review of SCLC patients that underwent cranial radiation therapy between January 2014 and June 2020 was performed to assess the impact of ICI therapy on time to BM development, overall survival (OS), and time to failure of BM treatment (defined as local or distant BM recurrence) using a multivariable Cox Proportional Hazards model. RESULTS Among 197 included patients, 23 patients (11.7%) received ICI before BM development. Extensive stage of SCLC at diagnosis was observed in eighteen patients (78.2%) in the ICI group and 133 (76.4%) in the non-ICI group. In total, seventeen patients (8.6%) received prophylactic cranial irradiation, of which seven patients (30.4%) also received ICI. ICI were associated with prolonged time to BM in comparison with the non-ICI group (HR = 0.29, 95% CI: 0.18-0.47). ICI were also associated with an increased OS (HR = 0.56, 95% CI: 0.32-0.97) and prolonged time to BM treatment failure (HR = 0.32, 95% CI: 0.15-0.71) in comparison with patients who did not receive ICI. CONCLUSION The use of ICI before BM development was associated with a longer time to BM. Additionally, ICI therapy was associated with an increased OS and prolonged BM treatment failure. These results are a proof of concept of the potential benefit of ICI therapy in SCLC patients, and the presented results should be further validated in larger cohorts.
Abstract 10094: National Trends in Deaths Due to Heart Disease and Cancer in the Elderly: 20 Year-Data
Authors: Abdul Minhas, Ahmed H Qavi, SALIK NAZIR, Sourbha Dani, Tariq Jamal Siddiqi, Muhammad Usman, Vincent M Figueredo, Marat Fudim
Journal: Circulation (2021)

Heart disease and cancer are the two leading causes of death in the United States. The aim of this study was to examine the trends in heart disease and cancer-related deaths in the elderly population in the United States from 1999 to 2019. Methods: The CDC Wide-ranging Online Data for Epidemiologic Research (CDC WONDER) was used to access the National Vital Statistics System data from 1999 to 2019. Heart and cancer-related deaths, age &gt;/=75 years, and sex were identified. Deaths were represented as age-adjusted mortality rates (AAMR) per 100,000 population. Joinpoint regression was used to examine changes in trend and annual percentage change (APC) overall. Results: AAMR related to heart disease decreased from 4587 in 1999 to 3235.6 in 2019 (average APC -1.8[95% CI, -1.9 to -1.6]). AAMR was higher in men (4375.6) than women (3287). Among the racial/ethnic groups, AAMR was highest in non-Hispanic Blacks (NHBs) (3926.2). APC in AAMR decreased across all the subgroups. After initial decline, the decrease in APC in AAMR decelerated overall (-0.7) and in both women (-0.9) and men (-0.7) since 2011. AAMR related to cancer decreased from 1770.51 in 1999 to 1379.91 in 2019 (average APC -1.3[95% CI, -1.3 to -1.2]). AAMR was higher in men (2104) than women (1262.7). Among the racial/ethnic groups, AAMR was highest in NHBs (1695.2). APC in AAMR decreased across all the subgroups. After an initial decline, the decrease in APC in AAMR accelerated overall (-1.5) and in men (-1.9) since 2007 and in women (-1.3) since 2006. Conclusion: Heart disease and cancer related mortality in elderly has been decreasing at a variable pace over the last twenty years. The decrease in the heart disease related mortality has decelerated in last several years whereas the decline in cancer related mortality has decelerated. Further research with targeted interventions in both these diseases is needed.
The POLARIX Study: Polatuzumab Vedotin with Rituximab, Cyclophosphamide, Doxorubicin, and Prednisone (pola-R-CHP) Versus Rituximab, Cyclophosphamide, Doxorubicin, Vincristine and Prednisone (R-CHOP) Therapy in Patients with Previously Untreated Diffuse Large B-Cell Lymphoma
Authors: Hervé Tilly, Franck Morschhauser, Laurie H. Sehn, Jonathan W. Friedberg, Marek Trněný, Jeff P. Sharman, Charles Herbaux, John M. Burke, Matthew Matasar, Shinya Rai, Koji Izutsu, Neha Mehta-Shah, Lucie Oberic, Adrien Chauchet, Wojciech Jurczak, Yuqin Song, Richard Greil, Larysa Mykhalska, Juan Miguel Bergua Burgués, Matthew C. Cheung, Antonio Pinto, Ho-Jin Shin, Greg Hapgood, Eduardo Munhoz, Pau Abrisqueta Costa, Jyh-Pyng Gau, Jamie Hirata, Yanwen Jiang, Mark Yan, Calvin Lee, Christopher R. Flowers, Gilles Salles
Journal: Blood (2021)
Abstract 10915: Unappreciated Mechanisms of Fatty Acid Uptake in the Kidney: Fatty Acids Are Taken Up from Both Basolateral and Apical Side
Authors: Ryo Kawakami, Hirofumi Hanaoka, Ayaka Kanai, Hideru Obinata, Miki Matsui, Hiroaki Sunaga, Hiroki Matsui, Norimichi Koitabashi, Tomoyuki Yokoyama, Masahiko Kurabayashi, Tatsuya Iso
Journal: Circulation (2021)

Introduction: The kidney combusts a large amount of fatty acid (FA) for body fluid homeostasis. Despite the high demand for FA, however, little is known about the mechanisms of FA uptake. We aimed to determine how FAs are taken up by tubular epithelial cells. Methods and Results: Immunohistochemistry showed that CD36, known as an important FA transporter in the heart, was also expressed in the basolateral side of proximal tubule epithelial cells (PTECs). The uptake of 125 I-BMIPP, radio-labeled FA tracer, was significantly reduced in the kidney in CD36 knockout mice 1 min after its injection compared with wild-type mice, while the significant difference disappeared 30 min after the injection. In vivo imaging with two-photon microscopy revealed that BODIPY-C 12 , fluorescence-labeled FA tracer, was accumulated in the basolateral side (blood side) of PTECs shortly after its injection, which was followed by accumulation in the apical side (primary urine side), suggesting bidirectional FA uptake by PTECs. A large amount of neutral lipid was accumulated in the kidney when serum FA concentration was increased by accelerated lipolysis by administration of a β3 adrenergic receptor agonist. Immunofluorescence with cell-specific antibodies revealed that the cells with the most abundant lipid accumulation were PTECs, followed by tubular epithelial cells of the distal nephron. In addition, neutral lipid accumulation was enhanced even in the distal nephron when PTECs were injured with administrations of diphtheria toxin (DT) in mice overexpressing DT-receptor in a PTEC-specific manner. Importantly, the PTEC-injured mice exhibited marked albuminuria, suggesting disturbance of protein reabsorption. Despite marked albuminuria, however, urinary FA was not detected at all, suggesting complete FA reabsorption independently of albumin reabsorption in the kidney. Conclusions: Our results revealed the unique and prominent capability of proximal and distal tubular epithelial cells to take up FA from both blood (CD36-dependent) and primary urine (CD36-independent) and to store them as neutral lipids. We further suggest that the kidney acts not only as FA consuming tissue but also as FA keeping tissue to completely reabsorb FA from primary urine for unwasted energy use.
RADT-10. DEVELOPMENT AND INTERNAL VALIDATION OF A PREDICTIVE SCORE FOR VERTEBRAL COMPRESSION FRACTURE AFTER STEREOTACTIC BODY RADIATION THERAPY FOR SPINAL METASTASES
Authors: Roman Kowalchuk, Benjamin Johnson-Tesch, Joseph Marion, Trey Mullikin, William Harmsen, Peter Rose, Brittany Siontis, Dong Kun Kim, Brian Costello, Jonathan Morris, Robert Gao, Satomi Shiraishi, John Lucido, Daniel Trifiletti, Kenneth Olivier, Dawn Owen, Bradley Stish, Mark Waddle, Nadia Laack, Sean Park, Paul Brown, Kenneth Merrell
Journal: Neuro-Oncology (2021)

Abstract PURPOSE Vertebral compression fracture (VCF) is a potential adverse effect following stereotactic body radiation therapy (SBRT) for spinal metastases. In this analysis, we developed and internally validated a risk stratification model for VCF. METHODS From an initial set of 680 treatments, we excluded those with proton therapy, prior surgical intervention, or missing data. The final dataset had 464 treatments in 313 patients. Delineations of VCF and all radiographic components of the spinal instability neoplastic score (SINS) were determined by a radiologist. Recursive partitioning analysis (RPA) was conducted using separate training (70%), internal validation (15%), and test (15%) sets. The log-rank test was used as the criterion for node splitting. RESULTS With a median follow-up of 21 months, we identified 84 VCF (18%), including 65 (77%) de novo and 19 (23%) progressive fractures. There was a median 9 months (IQR: 3 – 21) to VCF. From an initial set of 15 candidate variables, six were identified using the backwards selection method, feature importance testing, and a correlation heatmap. Four were then selected in the highest-fidelity RPA models: epidural tumor extension, lumbar location, gross tumor volume &amp;gt; 10 cc, and SINS &amp;gt; 6. One point was assigned to each variable, and the resulting multivariate Cox model had a concordance of 0.760. Each one point increase in score was associated with increasing rates of VCF. Low-risk lesions (score: 0-1, n=273) had 2-year freedom from VCF of 92%, compared to 80% for intermediate-risk (score: 2, n=99) and 56% (score: 3-4, n=92) for high-risk lesions (p &amp;lt; 0.0001). Cumulative incidence curves with death as a competing risk showed increased VCF with higher scores via Gray’s test (p &amp;lt; 0.001). CONCLUSIONS Our internally-validated model identifies a subgroup of patients with high risk for VCF who may benefit from prophylactic surgical stabilization or vertebroplasty.
BIOM-34. GENOMIC PROFILING IDENTIFIED COPY NUMBER VARIATIONS OF CDK4/6 AS A NOVEL PROGNOSTIC BIOMARKER FOR THALAMIC GLIOMA
Authors: Mingyao Lai, zhaoming Zhou, Hainan Li, Jiangfen Zhou, Juan Li, junjie Zhen, Cheng Zhou, Linbo Cai
Journal: Neuro-Oncology (2021)

Abstract BACKGROUND Thalamic glioma is a rare tumor, which is poorly understood in adults. The genetic variation of this tumor is still unknown. In this study, we investigated the mutation landscape of thalamic glioma and compared the clinical outcomes between different mutation situations in thalamic glioma. METHODS Next-generation sequencing targeting 425 cancer-relevant genes was performed with 34 thalamic glioma tissue samples. Gene mutations and copy number variations were investigated for prognostic effect with overall survival data. RESULTS Several diagnostic and prognostic biomarkers appeared in our thalamic glioma cohort, including TP53 (56%), EGFR (41%), TERT (35%), M CL1 (26%), PDGFRA (26%), PTEN (26%), CDK4/6 (24%), POLE (24%), PIK3CA (24%), NF1 (21%), ATR (21%), ATRX (18%), BRAF (15%), and ROS1 (12%). Among all genetic aberrations with a more than 10% occurrence rate, two mutations (TERT and PTEN) were associated with poor overall survival and one copy number variation (CDK4/6) was associated with favorable overall survival (univariate P &amp;lt; 0.1). Among these genes, CDK4/6 copy number variations (hazard ratio [HR], 0.16; 95% confidence interval [CI], 0.035–0.704; P = 0.016) remained significant survival associated in multivariate analyses. Copy number variations of CDK4/6 was seldom reported as a prognostic biomarker for glioma, especially for thalamic glioma in public databases. Besides, several gene mutations (BRIP1, MRE11A, MAP2K1, ROS1, MUTYH, JARID2, CTCF, and EGFR) were found positively associated with CDK4/6 copy number variations. Gene enrichment analysis demonstrated that those genes were related to astrocyte differentiation. CONCLUSIONS In our study, CDK4/6 copy number variation was determined as a favorable overall survival biomarker for thalamic glioma, and CDK4/6 copy number variation associated mutant genes were related to astrocyte differentiation, which could be the potential therapeutic targets for thalamic glioma.
Humoral Serologic Response to the BNT162b2 Vaccine Afterallogeneic Haematopoietic Cell Transplantation
Authors: Moshe Yeshurun, Oren Pasvolsky, Liat Shargian, Dafna Yahav, Maly Rubinstein, Michal Navon Sela, Ofir Wolach, Haim Ben-Zvi, Pia Raanani, Uri Rozovski
Journal: Blood (2021)
Abstract 13585: Red Flag Comorbid Conditions That Are Easily Extracted From the Electronic Health Record Often Precede Diagnosis of Cardiac Amyloidosis by Years
Authors: Joanna S Cavalier, Rahul Loungani, Michel G Khouri
Journal: Circulation (2021)

Introduction: With new and emerging disease-modifying therapies for cardiac amyloidosis (CA), there is a growing impetus for improved awareness and early diagnosis of this condition. Several groups have identified comorbid conditions, termed ‘red flag’ systemic symptoms and diagnostic findings, that occur commonly in patients with CA. To better understand the prevalence and temporal relationship of these ‘red flag’ comorbid conditions to a CA diagnosis, we used automated extraction of clinical data stored in the electronic health record (EHR) at a single institution. Methods: Patients with confirmed light-chain (AL) and transthyretin (ATTR) cardiac amyloidosis were identified at a single institution. The dates of diagnosis of ‘red flag’ comorbid conditions and for CA were extracted from the EHR via ICD-9 and ICD-10 codes, electrocardiogram intervals, and echocardiogram reports. Frequency and time between the diagnoses of red flags and CA were assessed. Results: Of 175 CA patients (85% ATTR), mean age was 72.7 years with majority (76.6%) male patients. Patients were most commonly black (52.6%) followed by Caucasian (42.3%). A diagnosis code for amyloidosis was found in 89.1% of patients, followed by heart failure in 84.6% of patients. ‘Red flag’ comorbid conditions were more likely to have been diagnosed before rather than after CA. When the ‘red flag’ was diagnosed prior to CA, the greatest average intervals between diagnoses were seen in carpal tunnel syndrome (8.3 years), spinal stenosis (5.9 years), and atrial fibrillation (2.8 years) (Table 1). Conclusions: EHR data from a single institution demonstrates that the diagnosis of CA is often delayed following the diagnosis of ‘red flag’ comorbid conditions. Our automated extraction of EHR data provides a foundational step in the ongoing development of an EHR-based warning score aimed at improving clinician awareness of the possibility of CA in appropriate patients.