tbuckley/cabot-search huggingface dataset:
Real-time assessment of resource utilization and subsequent cost analysis in cancer patients (pts) near the end of life (EOL).
Authors: Jordan P. McPherson, Shiven B. Patel, Elena Igumnova, Jacob Pettit, Dominik Ose, Tyler Haydell, Jim Martineau, Neal J. Meropol, Anna Catherine Beck
Journal: Journal of Clinical Oncology (2018)

303 Background: Aggressive medical interventions and associated high costs of care for cancer pts near the EOL are common. Addressing this issue at the local level requires an accurate, automated process to merge real-time clinical EHR data with cost data for performance reporting. Methods: This was a single-center, observational cohort study of decedents treated with anticancer therapy (antiCT) in the last 6 months of life from January 2016 to October 2017. Pts were stratified by antiCT use in the last 30 days of life. The primary outcome measure was total cost of care. Secondary outcome measures (hospitalizations, ER and ICU utilization, antiCT use, and hospice referral) were obtained through Flatiron Health EHR-based automated data processing. Cost data were merged from the Value-Driven Outcomes analytics framework. Results: 650 pts were included. 228 (35.1%) received antiCT in the 30 days before death. Non-drug costs for pts who received antiCT in the last 30 days of life were higher than those who did not (p &lt; 0.01, median 38X higher). A higher proportion of pts who received antiCT in the last 30 days of life had ≥1 ER visit (29.4% vs 9.5%, p &lt; 0.01) and hospital admission (58.8% vs 27.3%, p &lt; 0.01) during the last 30 days. In addition, more of these pts received ICU care (35.5% vs 11.4%, p &lt; 0.01). AntiCT in the last 30 days was associated with shorter median time from first hospice referral to death (1.4 vs 4.7 weeks; IQR 0.7-2.0 vs 3.14-7.7 weeks, p &lt; 0.01). Distribution of antiCT types administered to pts in the last 30 days versus those given antiCT &gt; 30 days from the EOL was significantly different, with the most substantial difference seen in the proportion of pts receiving immunotherapy (20.2% vs 12.6%, p = 0.04). Conclusions: Real-time assessment of EOL outcomes shows antiCT in the last 30 days of life is associated with aggressive medical interventions and increased total cost of care. Future research should identify pts who are unlikely to benefit from aggressive care, and whether performance reporting to oncologists will reduce futile interventions near the EOL.
Abstract 9851: Benefit of Antioxidant Peptide SS-31 Treatment in Attenuating Transverse Aortic Constriction-Induced Pulmonary Arterial Hypertension in Mice
Authors: Sheng-Ying Chung, Sarah Chua, Tzu-Hsien Tsai, Pei-Hsun Sung, Yung-Lung Chen, Steve Leu, Jiunn-Jye Sheu, Hon-Kan Yip
Journal: Circulation (2015)

Introduction: We investigated the effect of mitochondria-targeted antioxidant peptide SS-31 on transthoracic aortic constriction (TAC)-induced pulmonary arterial hypertension (PAH) in mice. Methods and Results: Adult-male mice (n=36) were equally divided into group 1 (sham-control), group 2 (TAC only), and group 3 (TAC-SS-31, 2 mg intra-peritoneal injection/day). By day 60, right ventricular systolic blood pressure (RVSBP) was measured prior to sacrificing the animals and the right heart and lung tissues were later collected. RVSBP was significantly higher in group 2 than in group 1, but the elevation was substantially suppressed in group 3 (p&lt;0.0001). Pulmonary protein expressions of oxidative-stress ((NOX-1, NOX-2, oxidized protein), cytosolic cytochrome-C, inflammation (MMP-9, TNF-α, NF-κB), calcium-overload-index (TRPC1, 2, 4, 6), apoptotic (mitochondrial BAX, cleaved caspase 3 and PARP), fibrotic (Smad3, TGF-β), hypoxic (HIF-1α), DNA-damage (γ-H2AX), and endothelial function-related (eNOS, ET-1R) biomarkers showed an identical pattern, whereas the anti-fibrotic (Smad1/5, BMP-2) markers and number of small vessels showed an opposite pattern compared to that of RVSBP among the three groups (all p&lt;0.001). The lung injury score, number of muscularized vessels in lungs, cellular expressions in PA (TRPC1+, HIF-1α+) and in lung parenchyma (γ-H2AX+, Ki-67+), showed an identical pattern, whereas the number of alveolar sacs showed an opposite pattern of RVSBP among the three groups (all p&lt;0.001). The protein expressions of anti-oxidants (HO-1, NQO 1, GR, GPx) were significantly progressively increased from groups 1 to 3 (all p&lt;0.001). Conclusion: Antioxidant peptide SS-31 effectively attenuated TAC-induced PAH in a murine model.
Ankyrin domain encoding genes from an ancient horizontal transfer are functionally integrated into Nasonia developmental gene regulatory networks
Authors: Daniel Pers, Jeremy A. Lynch
Journal: Genome biology (2018)

How regulatory networks incorporate additional components and how novel genes are functionally integrated into well-established developmental processes are two important and intertwined questions whose answers have major implications for understanding the evolution of development. We recently discovered a set of lineage-restricted genes with strong and specific expression patterns along the dorsal-ventral (DV) axis of the embryo of the wasp Nasonia that may serve as a powerful system for addressing these questions. We sought to both understand the evolutionary history of these genes and to determine their functions in the Nasonia DV patterning system.We have found that the novel DV genes are part of a large family of rapidly duplicating and diverging ankyrin domain-encoding genes that originated most likely by horizontal transfer from a prokaryote in a common ancestor of the wasp superfamily Chalcidoidea. We tested the function of those ankyrin-encoding genes expressed along the DV axis and found that they participate in early embryonic DV patterning. We also developed a new wasp model system (Melittobia) and found that some functional integration of ankyrin genes have been preserved for over 90 million years.Our results indicate that regulatory networks can incorporate novel genes that then become necessary for stable and repeatable outputs. Even a modest role in developmental networks may be enough to allow novel or duplicate genes to be maintained in the genome and become fully integrated network components.
Flu fighters: Flu vaccine administrations in pediatric hematology oncology patients.
Authors: Mehgan Beverley, Patricia Lorenz, Joel Kaplan, Nicole Turner
Journal: Journal of Clinical Oncology (2018)

131 Background: Influenza is a serious virus that affects millions of people every year. The CDC and AAP recommend all people starting 6 months of age get a yearly flu vaccine, especially the immunocompromised. Children receiving chemotherapy for cancer treatment are at heightened risk of severe influenza infection and resulting complications. (Goossen et al., 2013). Methods: An interdisciplinary team used the Model for Improvement with an aim statement, current and ideal process flow maps, and annotated run charts to monitor the impact of changes. Change ideas were tested via small-cycle PDSAs. Successful strategies included development of a flu form, targeting patients with pre-visit planning and phone calls, and escalation to physician intervention. Results: A p shewhart chart analyzed the percentage of target population receiving vaccines weekly. The goal was to vaccinate 95% of patients with leukemia or neuro-oncology on active chemotherapy who were older than 6 months of age without medical contraindications. At baseline, upper control limit (UCL) was 6%, mean was 2% and lower control limit (LCL) was 0%. After testing changes, the percentage of flu vaccines improved (special cause variation) to UCL 100%, mean 95%, LCL 87%. The goal was met and sustained through the end of 2018 flu season. This QI project also improved flu vaccinations given to all our patients as compared to the 2016/2017 flu season. During the 2016/2017 flu season, 295 flu vaccines were given. During the 2017/2018 flu season, 457 flu vaccines were given in a similar time frame, i.e. an increase of 155%. In addition to improving care delivered to our target population, this work facilitated greater distribution of flu vaccine to all at-risk populations in our clinic. Conclusions: This project shows a comprehensive and effective approach to reducing the risk of a serious health threat for some of our most vulnerable patients. By developing a well-defined process, standardizing messaging, and using data to inform next steps, our team surpassed benchmarks established by some of the best cancer care specialists in the country. The processes established here can be applied widely, offering hope that future flu seasons could be less devastating to vulnerable populations.
Abstract 19752: Nox4 Expression Regulates Inflammation in Tgfβ-treated Vascular Smooth Muscle Cells
Authors: Andrey Lozhkin, Aleksandr E Vendrov, Hua Pan, Samuel A Wickline, Nageswara R Madamanchi, Marschall S Runge
Journal: Circulation (2015)

NADPH oxidases (NOX) are a major source of reactive oxygen species in the cardiovascular system, contributing to the pathogenesis of disease. We recently reported that increased NOX4 expression in aging results in enhanced cellular and mitochondrial oxidative stress, vascular inflammation, dysfunction, and atherosclerosis. However, the role of NOX4 in the activation of inflammatory molecular pathways in vascular smooth muscle cells (VSMC) under pathophysiological conditions has not been elucidated. In this study, we investigated whether inhibition of NOX4 expression modulates proinflammatory gene expression in mouse VSMC by suppressing its expression with a novel peptide-mediated siRNA transfection approach. Using melittin derived peptide p5RHH, we achieved significantly higher transfection efficiency (92% vs 85% with Lipofectamine) and decreased toxicity (p&lt;0.01 vs Lipofectamine in MTT assay). TGFβ, a proinflammatory cytokine, known to induce NOX4 expression significantly upregulated NOX4 mRNA (p&lt;0.01) and protein expression (p&lt;0.01) in VSMC. p5RHH mediated NOX4 siRNA transfection attenuated TGFβ induced upregulation of NOX4 mRNA (p&lt;0.01) and protein (p&lt;0.01) levels. Analysis of inflammatory marker genes, CCL2, CCL5, IL6, and VCAM-1, showed that NOX4 knockdown significantly attenuated the expression of these genes in TGFβ-treated VSMC, with the highest inhibition seen in the expression of IL6. Congruent with this, inflammatory marker gene expression, which increases with aging, was significantly lower in VSMC isolated from aged (16 months old) NOX4 knockout mice compared with the aged wild-type. TGFβ-activated kinase 1 (TAK1, also known as MAP3K7) is an upstream regulator of inflammatory signaling in cells treated with cytokines. p5RHH mediated TAK1 siRNA transfection downregulated AP1 and NFκB activation and inhibited NOX4 expression in wild-type VSMC, indicating that TAK1 regulates NOX4 expression via regulation of AP1 and NFκB. Because plasma TGFβ levels increase with aging, it may be of one of the factors contributing to increased NOX4 expression with aging. Our data indicate that NOX4 is a potential therapeutic target for modulation of inflammation in aging and aging-associated cardiovascular disease.
Abstract 136: Cytoplasmic Histone Deacetylase 4 Promotes Vascular Calcification
Authors: Alon Abend, Omer Shkedi, Michal Fertouk, Lilac Caspi, Izhak Kehat
Journal: Circulation Research (2016)

Background: Arterial calcification and valvular calcifications are associated with significant morbidity and mortality. Studies have now conclusively showed that an osteochondrogenic differentiation of vascular smooth muscle cells (VSMC) is a key mechanism in the development of vascular calcification, opening a direction for therapeutic interventions. Objective: To identify the role, subcellular location and mechanism of action of class IIa Histone deacetylase 4 (HDAC4) in vascular calcification Methods and Results: We used VSMCs, ex-vivo mouse aortic rings and human calcified aortic valves to show that HDAC4 is upregulated in vascular and valve calcification. Despite being exclusively cytoplasmic in VSMCs we show using both gain- and loss- of function approaches that HDAC4 is a positive regulator of the process. The cytoplasmic location of HDAC4 is controlled by the activity of salt inducible kinase (SIK) and the inhibition of SIK sends HDAC4 to the nucleus and inhibits the ossification process. In the cytoplasm HDAC4 binds to the LIM domains of the adaptor protein ENIGMA (Pdlim7) to promote vascular ossification of VSMCs. Conclusions: Here we identified a new role and a new mechanistic paradigm for HDAC4. We provide multiple lines of evidence that the cytoplasmic activity of HDAC4 promotes vascular calcification, and identify HDAC4, SIK and ENIGMA as mediators of this pathological process
Assessing the impact of a digital coaching program for patients with cancer.
Authors: Uma Srivastava, Stephen Burton, M'Kayl Lewis, Dhiren Patel, Mazi Rasulnia
Journal: Journal of Clinical Oncology (2018)

274 Background: Cancer pain is found in 64% of patients with metastatic disease which can lead to negative effect on patient’s functional status which can then lead to psychological distress.Cancer pain can significantly affects an individual’s quality of life extending into mood or mental health and physical health.3 Various studies have shown that coaching is a useful strategy to address cancer pain and pain management. The hypothesis was by providing patients with cancer the Pack Health digital coaching solution, would lead to a reduction of cancer pain and increase in mental health over a 12 week intervention. Methods: This was a prospective study conducted between January 1, 2017 and December 31, 2017. 78 patients with cancer opted into the study, giving consent, and received intervention over 12 weeks. Patients were given standard print information and tools for self-care management in addition to a personal health advisor, who was in weekly communication with the participant to provide support, motivation, additional education, and accountability. Patient reported outcomes were collected using validated instruments, and patient satisfaction was measured using the Net Promoter Score (NPS). Results: The group was 86% female, and the average age was 55 years. Though not statistically significant, patients with a cancer diagnosis saw marginal improvements across some domains after 12 weeks. These results included a 15% decrease in perceived pain, 10% fewer prescreen for depression, and 11% more getting the recommended 7-9 hours of sleep each night. The slight decrease seen on average in both the mental health (-0.19%) or physical health (-0.30%) from the PROMIS Global-10 scores did not rise to the level of statistical significance. An NPS score of 69 for the program indicated strong patient satisfaction. Conclusions: Preliminary results illustrate that intensive behavioral counseling intervention help patients achieve their goals related to their chronic condition. The program showed adherence to health is linked to an increase in healthy habits leading eventually to an increase in patient’s overall health.
Thyroid Metastasis From Hepatocellular Carcinoma Visualized by 18F-FDG PET/CT Imaging
Authors: Hongyan Yin, Rongkui Luo, Yan Xiu, Yan Hu, Hongcheng Shi
Journal: Clinical Nuclear Medicine (2018)

Thyroid metastasis from hepatocellular carcinoma (HCC) is very rare. We present a case of a 41-year-old man with a markedly elevated serum α-fetoprotein (2,297 ng/mL) and a left neck mass 6 months after a hepatolobectomy for a primary HCC. F-FDG PET/CT imaging showed a focal uptake in the left thyroid lobe corresponding to a mass. The patient underwent a left hemithyroidectomy. Subsequent pathology confirmed HCC metastasis to the thyroid.
AB0908 Ability of the reductive x-ray score for psoriatic arthritis (REXSPA) to detect change in an observational cohort of patients with psa
Authors: A. Antony, A. Allard, G. Shaddick, D. Jadon, C. Cavill, E. Korendowych, N. McHugh, W. Tillett
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> The measurement of radiographic joint damage is important in characterising disease severity, progression, and prognosis in psoriatic arthritis (PsA). Existing radiographic measures are time-consuming to perform, leading to limited data collection from existing longitudinal observational studies. <h3>Objectives</h3> We have previously proposed a Reductive X-ray Score for Psoriatic Arthritis (ReXSPA)<sup>1</sup> as more feasible method, and in this study set out to examine the sensitivity of ReXSPA in a new cohort of patients. <h3>Methods</h3> A retrospective sample of 28 patients who had hand and feet radiographs at 3 time points (5 years before [T<sup>0</sup>], at the time of [T<sup>1</sup>], and 5 years post [T<sup>2</sup>] commencement of anti-TNF treatment) were taken from the Bath longitudinal PsA cohort. Radiographs were scored for erosion, joint space narrowing and proliferation to calculate the Sharp-van der Heijde modified method (VDH) and ReXSPA scores. A sample of 9 radiographs were scored by all assessors (WT, AA and AA) to determine inter- and intra-rater reliability using intra-class correlation coefficients (ICC). Sensitivity to change was determined from timepoint T<sup>0</sup> to T<sup>2</sup> using the Standardised Response Mean (SRM) and Smallest Detectable Change (SDC). <h3>Results</h3> The patients' mean age (SD) at T<sup>0</sup> was 61 years (13.4), the mean disease duration was 11.2 years (11.14). Patients were followed up for a mean (SD) of 10.2 years (2.76). Overall inter- and intra-rater reliability for ReXSPA and VDH were 0.80 and &gt;0.92 and 0.91 and &gt;0.90 respectively. The median (IQR) of ReXSPA score was 8.5 (1–14), 12.5 (5–20) and 14.5 (8–36) at T<sup>0</sup>, T<sup>1</sup>, and T2 respectively. The percentage SDC was 0.91 for the ReXSPA method and 0.77 for the VDH method, and the SRMs were 0.92 and 0.87 respectively (table 1), demonstrating the sensitivity of both methods in detecting change. There was a trend towards slowing in radiographic progression following the initiation of TNF-inhibitors, but ReXSPA was less sensitive compared to the VDH and was not able to detect a significant change in the rate of progression post-TNF inhibition (p 0.08) (Graphic 1). <h3>Conclusions</h3> The RexSPA is a reliable and sensitive alternate scoring method for the detection of radiographic progression in an observational cohort of patients with PsA, but not as sensitive to change as the VDH method. <h3>Reference</h3> [1] Tillett W, et al. (2016) Novel Composite Radiographic Score for Longitudinal Observational Studies of Psoriatic Arthritis: A Proof-of-concept Study. J Rheum; 43(2):367–370 <h3>Disclosure of Interest</h3> None declared
T-cell defects in patients with ARPC1B germline mutations account for combined immunodeficiency
Authors: Immacolata Brigida, Matteo Zoccolillo, Maria Pia Cicalese, Laurène Pfajfer, Federica Barzaghi, Serena Scala, Carmen Oleaga-Quintas, Jesus A. Álvarez-Álvarez, Lucia Sereni, Stefania Giannelli, Claudia Sartirana, Francesca Dionisio, Luca Pavesi, Marta Benavides-Nieto, Luca Basso-Ricci, Paola Capasso, Benedetta Mazzi, Jeremie Rosain, Nufar Marcus, Yu Nee Lee, Raz Somech, Massimo Degano, Giuseppe Raiola, Roberta Caorsi, Paolo Picco, Marcela Moncada Velez, Joelle Khourieh, Andrés Augusto Arias, Aziz Bousfiha, Thomas Issekutz, Andrew Issekutz, Bertrand Boisson, Kerry Dobbs, Anna Villa, Angelo Lombardo, Benedicte Neven, Despina Moshous, Jean-Laurent Casanova, José Luis Franco, Luigi D. Notarangelo, Cristina Scielzo, Stefano Volpi, Loïc Dupré, Jacinta Bustamante, Marco Gattorno, Alessandro Aiuti
Journal: Blood (2018)
Abstract 17377: Incidence of Atrial Fibrillation After Aortic Valve Replacement With a Bioprosthesis
Authors: Tuomas Kiviniemi, Markus Malmberg, Fausto Biancari, Juha Hartikainen, Leo Ihlberg, Fredrik Yannopoulos, Teemu Riekkinen, Juhani Airaksinen, Tuomo Nieminen
Journal: Circulation (2016)

Introduction: Atrial fibrillation (AF) is a frequent comorbidity in patients undergoing aortic valve replacement with a bioprosthesis. Hypothesis: The incidence of AF in the long-term follow-up pos...
Abstracts 1–410
Authors: Antigen Wegmann, L Cox, J Ertmann, P Swain, P Markovits, S Roodman, Crystal City, Senior High, M Bontempi, P Lasarte, A Velez, A Bakke, N Buist, R Campos, M Sato, Ajs Duarte
Journal: Journal of Allergy and Clinical Immunology (1997)
THU0377 Influence of undiagnosed vertebral fractures on organ damage in women with systemic lupus erythematosus
Authors: S. Shkireeva, O.M. Lesnyak, E.G. Zotkin
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Objectives</h3> To investigate the influence of asymptomatic vertebral fractures on organ damage and to identify risk factors associated with critical organ damage in women with systemic lupus erythematosus (SLE). <h3>Methods</h3> 197 women with SLE were included in this study. Bone mineral density (BMD) measurements of the hip and spine were performed using the dual energy X-ray absorptiometry (DXA). Vertebral fracture assessment (VFA) was done for detection vertebral fractures using a method described by Genant. Accumulated damage was scored using the SLICC/ACR damage index (SDI). Critical organ damage was defined as SDI&gt;3. <h3>Results</h3> Vertebral fractures were developed in 55 (27.9%) women with SLE. Half of all women with SLE (n=31, 15.7%) had asymptomatic vertebral fractures which were diagnosed for the first time in this study. 131 (66.5%) women with SLE had critical organ damage (SDI&gt;3). Average SDI before and after morphometry was 4,4±2,2 and 5,3±2,6 respectively. Multivariate analysis showed age (p=0,01), cumulative dose of glucocorticoids (p=0,00005), previous therapy with cyclophosphamide (p=0,04) were significantly associated with critical damage in women with SLE. <h3>Conclusions</h3> Detection of vertebral fractures helps in counting accumulated organ damage correctly. VFA in the combination with DXA in women with SLE is an effective method for diagnostic asymptomatic vertebral fractures. <h3>Disclosure of Interest</h3> None declared
Oversight of Patient-Centered Outcomes Research: Recommendations From a Delphi Panel
Authors: Luke Gelinas, Joel S. Weissman, Holly Fernandez Lynch, Avni Gupta, Ronen Rozenblum, Emily A. Largent, I. Glenn Cohen
Journal: Annals of Internal Medicine (2018)

A key aim of patient-centered outcomes research (PCOR) is to generate data that are important to patients by deliberately and extensively involving them in all aspects of research, from design to dissemination. However, certain elements of PCOR raise challenging and potentially novel ethical and regulatory issues for institutional review boards and oversight bodies. These challenges stem primarily from the engagement of patients in roles other than research subject, such as advisors, study personnel, and co-investigators, which gives rise to questions about appropriate levels of protection, training, and education, as well as identifying and managing conflicts of interest. This article presents and discusses recommendations from a Delphi expert panel that was convened to address these and other PCOR-related oversight challenges.