tbuckley/cabot-search huggingface dataset:
Abstract 002: Circulating Levels of Natural Killer Cells and Monocyte Subsets Are Associated With Higher Systolic Blood Pressure: The Multi-Ethnic Study of Atherosclerosis
Authors: Margaret F Doyle, Colleen M Sitlani, Nels C Olson, Sally A Huber, Alan L Landay, Russell P Tracy, Bruce M Psaty, Joseph A Delaney
Journal: Circulation (2018)

Introduction: Hypertension is a multifactorial process. Activation of the innate immune system and subsequent upregulation of adaptive immunity have been shown to promote hypertension in various mouse models Large scale human population studies examining the composition of the innate and adaptive immune system as it pertains to hypertension are lacking. Hypothesis: The composition of innate and adaptive immune cells are risk factors for increased systolic blood pressure (SBP). Methods: Using cells cryopreserved from the baseline exam, we measured 34 immune cell subsets from participants of the Multi-Ethnic Study of Atherosclerosis (MESA) (mean age 64 years, 53% male), sampled from a case-cohort study of myocardial infarction (n=1,200). SBP was assessed at baseline and at four follow-up exams over the succeeding ten years. Our approach to anti-hypertensive medication use was to add 10mmHG to SBP for treated participants. Associations between immune cell subpopulations and SBP were conducted using linear mixed models, with sampling weights to account for the sampling strategy and robust confidence intervals; immune cells were modeled per standard (SD) deviation higher value. We adjusted for age, sex, race/ethnicity, smoking, exercise, body mass index, education, diabetes, and log- transformed cytomegalovirus levels. Results: After adjustment for potential confounders, 5 of 34 immune cells subsets were significantly associated with mean levels of SBP. For each standard deviation increment higher immune cell proportion, natural killer (NK) cells, defined as CD3-CD56+CD16+, (1.9 mmHG; 95% CI: 0.8-2.9), classic monocytes, defined as CD14++CD16-, (-1.3 mmHG; 95% CI: -2.5 to -0.1) and non-classic monocytes, defined as CD14+CD16++, (1.4 mmHG; 95% CI: 0.3 to 2.6) had the strongest associations with SBP changes over 10-years of follow-up. Sensitivity analyses with principal components analysis were supportive of these findings. After using a Bonferroni corrected threshold to account for for multiple testing only NK remained significant. Conclusions: NK cells, classic monocytes and non-classic monocytes, all components of the innate immune system, were associated with higher levels of SBP over follow-up. The strongest association was with natural killer cells; in agreement with previous studies that showed circulating levels of interferon gamma and tumor necrosis factor alpha, the two main cytokines produced by NK cells, correlate with systolic blood pressure.
Survival After Stereotactic Body Radiation Therapy for Clinically Diagnosed or Biopsy-Proven Early-Stage NSCLC: A Systematic Review and Meta-Analysis
Authors: Michiel A. IJsseldijk, Melina Shoni, Charles Siegert, Bastiaan Wiering, K.C. Anton van Engelenburg, Abraham Lebenthal, Richard P.G. ten Broek
Journal: Journal of Thoracic Oncology (2019)
Overall Survival and Response Rates after a 10-Year Follow-up of Chronic Myeloid Leukemia Patients in Chronic Phase Treated with Imatinib in a Real-Life Practice
Authors: Matteo Molica, Emilia Scalzulli, Alunni Fegatelli Danilo, Roberto Latagliata, Gioia Colafigli, Lorenzo Rizzo, Daniela Diverio, Robin Foà, Massimo Breccia
Journal: Blood (2018)
Identification of site-specific genome alterations in metastatic colorectal cancer: Sub-study 003 of the SCRUM-Japan GI-SCREEN.
Authors: Takuro Mizukami, Masaki Takahashi, Yu Sunakawa, Satoshi Yuki, Yoshinori Kagawa, Atsuo Takashima, Kyoko Kato, Hiroki Hara, Tadamichi Denda, Toshikazu Moriwaki, Manabu Shiozawa, Eiji Oki, Taroh Satoh, Hisato Kawakami, Taito Esaki, Tomohiro Nishina, Wataru Okamoto, Takayuki Yoshino, Takako Eguchi Nakajima
Journal: Journal of Clinical Oncology (2019)

578 Background: Primary tumor sidedness is known to be an independent prognostic factor and a predictor for the efficacy of anti-EGFR antibody. However, limited information is available regarding the role of primary tumor site for the treatment of metastatic colorectal cancer (mCRC) patients (pts), including gene mutation profiles, prognosis, and prediction for treatment. This study was conducted as a sub-study of the SCRUM-Japan GI-SCREEN, the Nationwide Cancer Genome Screening Project in Japan. Methods: Among participants of the GI-Screen 2013-01-CRC, untreated pts with mCRC which samples were collected from primary site were eligible. DNA and RNA were extracted from FFPE tumor samples and then were analyzed by the Oncomine Cancer Research Panel detecting gene mutations, copy number variants (CNV), and fusions across 143 genes in a CLIA certified CAP accredited laboratory. The detected genomic variant data were classified according to genetic drivers of cancer including gain- and loss-of-function or single nucleotide variant based on the Oncomine Knowledgebase. Results: Among 1011 enrolled pts from Feb. 2015 to Mar 2017, a total of 561 samples were analyzed (median age, 66.0 years; 232 [41.4 %] female). Frequency of female, undifferentiated, mucinous or signet ring cell subtype were gradually increased as the primary site became the right side. Median site-specific survival was 22.4 months (m) in the cecum, 25.3 m in the ascending colon, 21.2 m in the transverse colon, 72.5 m in the descending colon, 36.5 m in the sigmoid colon, and 39.6 m in the rectum. Gene alterations differed in each primary site. Among frequently observed gene alterations, FBXW7 mutation in rectum, ATM mutation in transverse colon, BRAF and SMAD4 mutations in ascending colon significantly contributed to poor prognosis. Conclusions: This study revealed the site-specific survival and gene alterations in Japanese mCRC pts. These novel knowledges provide an intriguing background to investigate new targeted approaches in these pts and represent the progress toward precision medicine. We will analyze the site-specific therapeutic effect of molecular targeting agents, including anti-EGFR antibody. Clinical trial information: UMIN000031242.
Pomalidomide (POM) and Low-Dose Dexamethasone (LoDEX) in Relapsed/Refractory Multiple Myeloma (RRMM): Analysis of Real World Data from an Ongoing, National, Multi-Center, Non-Interventional Study
Authors: Daniel Lechner, Richard Greil, Bernd Hartmann, Maria-Theresa Krauth, Heinz Gisslinger, Ursula Vogl, Leopold Ohler, Hildegard T. Greinix, Siegfried Sormann, Johannes Andel, Ernst Rechberger, Hermine Agis
Journal: Blood (2018)
Treatment of Immune Thrombocytopenia (ITP) with Eltrombopag (EPAG) in Patients Who Did and Did Not Receive Prior Rituximab (Ritux): A Post-Hoc Analysis of the Extend Study
Authors: Oliver Meyer, James B. Bussel, Raymond S Wong, Abderrahim Khelif, Miona Stankovic, Joan Maier, Mansoor N. Saleh
Journal: Blood (2018)
Expression of PD-L1 in Leukemic Progenitor Cells Defines NPM1 Mutated AML As a Potential Subgroup for PD1/PD-L1 Directed Immunotherapy
Authors: Jochen Greiner, Vanessa Schneider, Hubert Schrezenmeier, Markus Wiesneth, Lars Bullinger, Hartmut Döhner, Susanne Hofmann, Marlies Götz
Journal: Blood (2018)
Rapid Nasal Symptom Onset of Action and Ocular Symptom Relief With Olopatadine/Mometasone Combination Nasal Spray in Patients with Seasonal Allergic Rhinitis: A Pooled Analysis
Authors: Bruce Prenner, Frank Hampel, Nelumka Fernando, Cynthia F. Caracta, Sudeesh K. Tantry
Journal: Journal of Allergy and Clinical Immunology (2019)
Diet modulates colonic T cell responses by regulating the expression of a <i>Bacteroides thetaiotaomicron</i> antigen
Authors: Marta M. Wegorzewska, Robert W. P. Glowacki, Samantha A. Hsieh, David L. Donermeyer, Christina A. Hickey, Stephen C. Horvath, Eric C. Martens, Thaddeus S. Stappenbeck, Paul M. Allen
Journal: Science Immunology (2019)

T cell responses to symbionts in the intestine drive tolerance or inflammation depending on the genetic background of the host. These symbionts in the gut sense the available nutrients and adapt their metabolic programs to use these nutrients efficiently. Here, we ask whether diet can alter the expression of a bacterial antigen to modulate adaptive immune responses. We generated a CD4+ T cell hybridoma, BθOM, specific for Bacteroides thetaiotaomicron (B. theta). Adoptively transferred transgenic T cells expressing the BθOM TCR proliferated in the colon, colon-draining lymph node, and spleen in B. theta-colonized healthy mice and differentiated into regulatory T cells (Tregs) and effector T cells (Teffs). Depletion of B. theta-specific Tregs resulted in colitis, showing that a single protein expressed by B. theta can drive differentiation of Tregs that self-regulate Teffs to prevent disease. We found that BθOM T cells recognized a peptide derived from a single B. theta protein, BT4295, whose expression is regulated by nutrients, with glucose being a strong catabolite repressor. Mice fed a high-glucose diet had a greatly reduced activation of BθOM T cells in the colon. These studies establish that the immune response to specific bacterial antigens can be modified by changes in the diet by altering antigen expression in the microbe.
Real-World Costs of Continuous Insulin Pump Therapy and Multiple Daily Injections for Type 1 Diabetes: A Population-Based and Propensity-Matched Cohort From the Swedish National Diabetes Register
Authors: Emilie Toresson Grip, Ann-Marie Svensson, Mervete Miftaraj, Björn Eliasson, Stefan Franzén, Soffia Gudbjörnsdottir, Katarina Steen Carlsson
Journal: Diabetes Care (2019)

To investigate real-world costs of continuous insulin pump therapy compared with multiple daily injection (MDI) therapy for type 1 diabetes.Individuals with type 1 diabetes and pump therapy in the Swedish National Diabetes Register (NDR) since 2002 were eligible. Control subjects on MDI were matched 2:1 using time-varying propensity scores. Longitudinal data on health care resource use, antidiabetes treatment, sickness absence, and early retirement were taken from national registers for 2005-2013. Mean annual costs were analyzed using univariate analysis. Regression analyses explored the role of sociodemographic factors. Subgroup and sensitivity analyses were performed.A total of 14,238 individuals with type 1 diabetes entered in the NDR between 2005 and 2013 (insulin pump n = 4,991, MDI n = 9,247, with switches allowed during the study) were included. Mean age at baseline was 34 years, with 21 years of diabetes duration and a mean HbA1c of 8.1% (65 mmol/mol). We had 73,920 person-years of observation with a mean follow-up of 5 years per participant. Mean annual costs were higher for pump therapy than for MDI therapy ($12,928 vs. $9,005, respectively; P < 0.001; mean difference $3,923 [95% CI $3,703-$4,143]). Health care costs, including medications and disposables, accounted for 73% of the costs for pump therapy and 63% of the costs for MDI therapy. Regression analyses showed higher costs for low education, low disposable income, women, and older age.Nine years of real-world data on all measurable diabetes-related resource use show robust results for additional costs of insulin pump therapy in adults by subgroup and alternative propensity score specifications. Identification of tangible and intangible benefits of pump therapy over time remain important to support resource allocation decisions.
Surveillance for locally advanced esophageal and gastroesophageal junction (GEJ) cancers: Patterns of recurrence and methods of detection.
Authors: Jubin Eghbali Matloubieh, Alexandra Pilar Licona-Freudensten, Andrea M Baran, Michal J Lada, Carolyn E Jones, Christian G Peyre, Aram F Hezel, Marcus Smith Noel, Richard Francis Dunne, Mohamedtaki Abdulaziz Tejani
Journal: Journal of Clinical Oncology (2019)

32 Background: Trimodality treatment with neoadjuvant chemoradiation (CRT) followed by surgery is a standard treatment for esophageal/GEJ (E/GJ) cancers. Following esophagectomy, there is no strong consensus about optimal surveillance and routine imaging. At our institution, patients have surveillance CT scans every 4-6 months for the first 2 years post-surgery and every 6-12 months for the next 3 years. Methods: An IRB-approved chart review was performed identifying patients who underwent surgical resection for locally advanced E/GJ cancer between January 2011 and December 2015 at the University of Rochester. Study objectives were to describe timing of and methods used to detect recurrence as well as their impact on patient outcomes. Recurrence-free (RFS) and overall survival (OS) were graphed via the Kaplan-Meier method. Results: 138 patients underwent surgical resection for E/GJ cancer during the study period: 107 (77.5%) were male, median age was 64, and 116 patients (84.1%) had adenocarcinoma. 111 patients (80.4%) received neoadjuvant CRT. Median OS for entire cohort was 43.4 months. 65 patients (47.1%) relapsed with a median RFS of 19.8 months. Recurrence was detected by routine imaging in 34 patients (52.3%), imaging triggered by symptoms in 25 patients (38.5%), and symptoms alone in 6 patients (9.2%). Median OS post-relapse was 1.5 months when detected based on symptoms alone, 5.0 months when detected by imaging triggered by symptoms, and 13.5 months when detected by routine scans (Log-rank p = 0.046). There were no significant associations between baseline patient /tumor characteristics and subsequent method of recurrence detection. Conclusions: 47.1% of patients suffered relapse after trimodality therapy for E/GJ cancer, consistent with published literature. Almost half of these were detected based on symptoms despite routine imaging. Increased OS for patients with relapse detected by routine scans is likely related to lead time bias, but may be related to increased treatment intensity, or due to less aggressive tumors. Prospective randomized trials are needed to determine the true benefit of regular surveillance scans among esophageal cancer survivors.
Cytokine Release Syndrome after Allogeneic Stem Cell Transplantation with Post Transplant Cyclophosphamide
Authors: Laura Solán, Elena Landete, Rebeca Bailén, Nieves Dorado, Pascual Balsalobre, David Serrano, Carolina Martínez-Laperche, Javier Anguita, Jose Luis Díez-Martín, Mi Kwon
Journal: Blood (2018)
Eye Care Utilization Among Insured People With Diabetes in the U.S., 2010–2014
Authors: Stephen R. Benoit, Bonnielin Swenor, Linda S. Geiss, Edward W. Gregg, Jinan B. Saaddine
Journal: Diabetes Care (2019)

OBJECTIVE Diabetic retinopathy (DR) is the leading cause of blindness among working-age adults, and although screening with eye exams is effective, screening rates are low. We evaluated eye exam visits over a 5-year period in a large population of insured patients 10–64 years of age with diabetes. RESEARCH DESIGN AND METHODS We used claims data from IBM Watson Health to identify patients with diabetes and continuous insurance coverage from 2010 to 2014. Diabetes and DR were defined using ICD-9 Clinical Modification codes. We calculated eye exam visit frequency by diabetes type over a 5-year period and estimated period prevalence and cumulative incidence of DR among those receiving an eye exam. RESULTS Among the 298,383 insured patients with type 2 diabetes and no diagnosed DR, almost half had no eye exam visits over the 5-year period and only 15.3% met the American Diabetes Association (ADA) recommendations for annual or biennial eye exams. For the 2,949 patients with type 1 diabetes, one-third had no eye exam visits and 26.3% met ADA recommendations. The 5-year period prevalence and cumulative incidence of DR were 24.4% and 15.8%, respectively, for patients with type 2 diabetes and 54.0% and 33.4% for patients with type 1 diabetes. CONCLUSIONS The frequency of eye exams was alarmingly low, adding to the abundant literature that systemic changes in health care may be needed to detect and prevent vision-threatening eye disease among people with diabetes.
Abstract 12085: Arrhythmogenic Effects of Cardiac Mesenchymal Stem Cell Implantation: Results From the POSEIDON and TAC-HFT Trials
Authors: Archana Ramireddy, Chad R Brodt, Darcy L DiFede, Adam M Mendizabal, James O Coffey, Juan F Viles-Gonzalez, Alan W Heldman, Robert J Myerburg, Joshua M Hare, Raul D Mitrani
Journal: Circulation (2014)

Introduction: Transendocardial injection of mesenchymal stem cells (MSC) in patients (pts) with ischemic cardiomyopathy (ICM) improves left ventricular function and structure, but it is unknown whe...
Vitamin D receptor–mediated skewed differentiation of macrophages initiates myelofibrosis and subsequent osteosclerosis
Authors: Kanako Wakahashi, Kentaro Minagawa, Yuko Kawano, Hiroki Kawano, Tomohide Suzuki, Shinichi Ishii, Akiko Sada, Noboru Asada, Mari Sato, Shigeaki Kato, Kotaro Shide, Kazuya Shimoda, Toshimitsu Matsui, Yoshio Katayama
Journal: Blood (2019)
Clinical outcomes of hepatocellular carcinoma variants compared to hepatocellular carcinoma.
Authors: Katerina Mary Zakka, Renjian Jiang, Olatunji B. Alese, Walid Labib Shaib, Christina Wu, Joel Wedd, Marty T. Sellers, Madhusmita Behera, Bassel F. El-Rayes, Mehmet Akce
Journal: Journal of Clinical Oncology (2019)

435 Background: There is no consensus regarding treatment for HCC variants. Clinical outcomes of HCC variants differ from pure HCC. The aim of this study is to compare clinicopathological characteristics, treatment, and outcomes of HCC variants with pure HCC. Methods: Patients with HCC and variants with 8170/3-8175/3 and 8180/3 ICD-O-3 codes were identified from National Cancer Database between 2004 and 2013. Univariate and multivariate survival analyses were conducted to analyze the association between histology and overall survival (OS). Results: 80,280 patients were identified; pure HCC 78,461 (97.7%), fibrolamellar (FLHCC) 310 (0.4%), scirrhous 161 (0.2%), spindle cell 72 (0.1%), clear cell 487 (0.6%), pleomorphic 23 (0.0%), and combined HCC and cholangiocarcinoma (mixed HCC) 766 (1.0%). 76.7% were male and 72% Caucasian. The mean age was similar in all except FLHCC (37.9 vs. 60.9-64.1 years, p &lt; 0.001). Liver transplant was performed in 10.1% of pure HCC, 14.5% of mixed HCC, 16.2% of scirrhous, 6.9% of spindle cell, 8.8% of clear cell, 8.7% of pleomorphic, and 3.2% of FLHCC (p &lt; 0.001). Pure HCC (10.57%) underwent surgical resection less often than variants; FLHCC (54.8%), clear cell (34.5%), mixed HCC (29.8%), spindle cell (33.3%), pleomorphic (34.8%), and scirrhous (9.9%) (p &lt; 0.001). Ablation was performed in 9.8% of pure HCC, and in up to 8.7% of HCC variants. More than a third of all patients received chemotherapy; pure HCC (42.3%), mixed HCC (38.5%), scirrhous (31.1%), spindle cell (36.1%), clear cell (35.5%), pleomorphic (34.8%), and FLHCC (41.3%). FLHCC had the best 5-year OS (38.7%), spindle cell and pleomorphic had the worst (9.6% and 13.0%). In univariate and multivariate analyses, fibrolamellar histology, female sex, diagnosis between 2009 and 2013, treatment at academic center, well/moderately differentiated histology, early stage, and chemotherapy was associated with better OS compared to pure HCC, male sex, diagnosis between 2004 and 2008, treatment at community cancer program, poorly differentiated, late stage, and no chemotherapy (p &lt; 0.001). Conclusions: HCC variants underwent surgical resection more often than HCC. FLHCC had the best 5-year OS. Liver transplant is commonly performed in HCC variants.
Abstract 18052: Platelet Activity in Primary Percutaneous Coronary Intervention Patients Randomized to Bivalirudin or Heparin
Authors: Dimitrios Venetsanos, Eva Swahn, Sofia Sederholm Lawesson, Kerstin M Gustafsson, David Erlinge, Tomas L Lindahl, Joakim Alfredsson
Journal: Circulation (2017)

Introduction: In previous studies, bivalirudin compared to unfractionated heparin (UFH) significantly suppressed platelet activity in planned PCI after pretreatment with clopidogrel. However, it is unclear if bivalirudin confers any additional antiplatelet effect compared with UFH in STEMI patients pretreated with ticagrelor. Hypothesis: Bivalirudin, as compared to UFH, further inhibits platelet activity in STEMI patients treated with ticagrelor. Methods: In this substudy of the VALIDATE-SWEDEHEART trial, 103 patients pretreated with ticagrelor, were randomly assigned to bivalirudin or UFH. Blood samples were collected at randomisation (baseline) and at 1 and 12 hours. Platelet aggregation was measured with Multiplate. High residual platelet reactivity (HRPR) was defined as ADP-stimulated AUC units > 46. Soluble p-selectin and thrombin anti-thrombin complex (TAT) were also measured. Results: The two groups were well balanced in baseline characteristics. Median (IQR) time from ticagrelor loading dose to ra...
Targeted Treatment of <i>TREX1</i> Chilblain Lupus and Other Interferonopathies—Taming T REX
Authors: William Damsky, Brett A. King
Journal: JAMA Dermatology (2019)

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Reliability of endoscopic biopsy compared with endoscopic submucosal dissection histopathologic diagnosis.
Authors: Kyuwon Lee, Tae Ho Kim
Journal: Journal of Clinical Oncology (2019)

15 Background: Endoscopic biopsy is the most convenient and simple method for approaching gastric neoplasm. Aim of our study was to determine the diagnostic accuracy of biopsy during screening endoscopy compared to endoscopic submucosal dissection (ESD). Methods: 175 patients who underwent both screening endoscopic biopsy and ESD from 2015.01 to 2017.12 in Bucheon St. Mary’s hospital were retrospectively reviewed. Results: Seventeen lesions had different histopathological ESD findings compared with endoscopic biopsy. Among six endoscopic biopsies that showed atypia, four were diagnosed with adenocarcinoma and two maintained the results. 64 out of the 175 lesions showed low grade dysplasia by endoscopic biopsy. After ESD, two cases were diagnosed with high grade dysplasia and two cases were diagnosed with adenocarcinoma. Of 12 lesions which showed high grade dysplasia on endoscopic biopsy, four lesions turned out to be adenocarcinoma (three well differentiated, one moderately differentiated) after ESD. Of 91 adenocarcinoma lesions on endoscopic biopsy, three lesions had discrepancy on differentiation level and one lesion turned out to be signet ring cell carcinoma after all. Patients who were infected with Helicobacter pylori (H. pylori) had tendency to have discrepancy between initial biopsy and ESD histopathology result. (OR 3.68, 95% CI 1.08-11.955, P = 0.018). Conclusions: Discrepancy between endoscopic biopsy and post-ESD histopathology were found. Possibility of coexistence or progression to high grade neoplasm should be considered regarding endoscopic biopsy results especially if infected with H. pylori and active ESD histopathological confirmation needs to be done if necessary.