tbuckley/cabot-search huggingface dataset:
Long‐term improvement in cardiac magnetic resonance in β‐thalassemia major patients treated with deferasirox extends to patients with abnormal baseline cardiac function
Authors: Maddalena Casale, Aldo Filosa, Alfonso Ragozzino, Giovanni Amendola, Domenico Roberti, Immacolata Tartaglione, Elisa De Michele, Domenico Cozzolino, Giuliana Rispoli, Francesco Palmieri, Umberto Pugliese, Saverio Scianguetta, Giuseppe Signoriello, Khaled M. Musallam, Silverio Perrotta
Journal: American Journal of Hematology (2018)

The management of iron overload in thalassemia has changed dramatically since the implementation of magnetic resonance imaging, which allows detection of preclinical iron overload and prevention of clinical complications. This study evaluated the effect of deferasirox (DFX), the newest once-daily oral chelator, on cardiac function, iron overload and cardiovascular events over a longer follow up in a "real world" setting. Longitudinal changes in cardiac magnetic resonance T2*, cardiac function parameters and cardiovascular clinical events were assessed in a cohort of 98 TM patients exposed to DFX for a mean of 6.9 years (range 1.8-11.6 years). No cardiac death or incident heart failure occurred. Cardiac T2* significantly increased (+2.6 ± 11.9 msec; P = 0.035) in the whole population, with a significantly greater increase (+11.6 ± 15.5 msec, P = 0.019) in patients with cardiac iron overload (T2* <20 ms). A significant improvement in left-ventricular ejection fraction (LVEF) (from 50.6 ± 6 to 60.2 ± 5; P = 0.001) was observed in 11 (84.6%) out of 13 patients who normalized cardiac function (LVEF >56%). Arrhythmias were the most frequent cardiac adverse event noted but none led to DFX discontinuation. Our data indicate that DFX is effective in maintaining cardiac iron level in the normal range and in improving cardiac iron overload. No heart failure or cardiac death was reported over this longer observation up to 12 years. For the first time, a DFX-induced improvement in LVEF was observed in a subgroup of patients with abnormal cardiac function at baseline, a preliminary observation which deserves further evaluation.
Lung cancer: Significance of place of diagnosis.
Authors: Rohit Bishnoi, Chintan Shah, Jacobo Hincapie Echeverri, Katherine Robinson, Yu Wang, Ji-Hyun Lee, Jessica Marie Schmit
Journal: Journal of Clinical Oncology (2018)

60 Background: Patients who are diagnosed with lung cancer through emergency department tend to do poorly. We conducted a retrospective study to examine the effect of place of diagnosis on various cancer outcomes including survival, health care cost, and end-of-life (EOL) care. Methods: Patients who died from lung cancer between January 2015 and July 2017 were reviewed. Initial place of diagnosis was determined (Emergency Department/Urgent clinic (ED/UC) or Outpatient). Descriptive statistics, exact Pearson chi-square test, Kaplan-Meier method, and multivariable Cox regression model were used to compare the two groups. Results: 227 patients were included in the analysis. Median age at diagnosis was 65 years. 52% were male; 85% were white. 57% of patients were diagnosed through ED/UC, whereas 43% were diagnosed as part of an outpatient workup. Age, gender, race, and histology (small cell vs. non-small cell) did not vary significantly between the two groups. Rates of palliative care intervention and advance directives were similar. Patients diagnosed through ED/UC were more likely to be metastatic, have symptoms, and not receive any cancer directed therapy. Cost of care was similar between the two groups. Median survival in those who presented to ED/UC was significantly shorter (2.5 vs. 6.5 mo; p&lt;0.001) with a hazard ratio of 1.7 (95% CI:1.3-2.3), even after adjusting for potential confounding factors (age, metastasis, insurance, smoking, treatment). Conclusions: Patients diagnosed with lung cancer through the ED/UC have worse outcomes than those diagnosed as an outpatient. Despite similar cost of care, survival outcomes are worse. This variable remains significant despite controlling for confounders in multivariate analysis.[Table: see text]
A Next-Generation Sequencing-Based Karyotyping Algorithm Reveals the Genomic Structure of Acute Myeloid Leukemia
Authors: Dean Pavlick, Meagan Montesion, Nyla A. Heerema, Eric A Severson, Timothy Brennan, Garrett M Frampton, Jie He, John C. Byrd, Ross L. Levine, Amy Burd, Jo-Anne Vergilio, Lee A Albacker
Journal: Blood (2018)
Argx-110 Targeting CD70, in Combination with Azacitidine, Shows Favorable Safety Profile and Promising Anti-Leukemia Activity in Newly Diagnosed AML Patients in an Ongoing Phase 1/2 Clinical Trial
Authors: Adrian F Ochsenbein, Carsten Riether, Ulrike Bacher, Rouven Müller, Sabine Höpner, Yara Banz, Magdalena Hinterbrandner, Mario Bargetzi, Markus G. Manz, Luc Van Rompaey, Mahan Moshir, Tim Delahaye, Domenica Gandini, Ellen Erzeel, Anna Hultberg, Samson Fung, Hans De Haard, Nicolas Leupin, Thomas Pabst
Journal: Blood (2018)
Montague W M Hadley
Authors: Donald Hadley, Louise Roy, Aileen Taylor, Sheena Allan
Journal: BMJ (2018)

Montague W M Hadley (“Monty”) was born in Inverness, after a prenatal dash by his dentist mother from West Bromwich to ensure her child's Scottish and Inverness heritage. During his medical residency at Inverness Royal Infirmary, Monty met fellow resident Dorothy Reside, who would later become his wife. He joined the Royal Army Medical Corps in 1945 and was posted to Ranchi, India, for two …
The Future of Health Care Reform — A View from the States on Where We Go from Here
Authors: David K. Jones, Christina Pagel, Christopher F. Koller
Journal: New England Journal of Medicine (2018)

Interview with Dr. David Jones on the possibilities for finding solutions to health policy problems at the state level. (11:33)Download What does a solutions-oriented conversation about U.S. health care look like at the state level, how do we get there, and what does a shift toward state action mean for the future of reform? State legislators in Colorado and Kansas have provided some provocative answers.
Potential mechanisms for the cytotoxicity elicited by the combination of EGCG and raloxifene in MDA-MB-231 cells
Authors: Emma Stuart, Reagan Jarvis, Rhonda Rosengren
Journal: Cancer Research (2008)

1479  Previously we have shown that epigallocatechin gallate (EGCG) (25 μM) and 4-OH tamoxifen (4-OHT) (1 μM) are synergistically cytotoxic toward MDA-MB-231 ERα negative human breast cancer cells. Furthermore, studies have shown that raloxifene is cytotoxic in a number of cancer cell lines. We aimed to determine if the synergistic effect observed with the combination of EGCG and 4-OHT is observed in combination with raloxifene. The sulforhodamine B assay was used to determine changes in cell number. After 7 days of treatment, EGCG (25 μM) and raloxifene (4 μM) were shown to synergistically decrease cell number by 76 ± 3.8% from control, and time-course studies demonstrated that a significant repression (p
Androgen Deprivation Therapies and Changes in Comorbidity: A Comparison of Gonadotropin-releasing Hormone Agonists and Antiandrogen Monotherapy as Primary Therapy in Men with High-risk Prostate Cancer
Authors: Kerri Beckmann, Hans Garmo, Jan Adolfsson, Cecilia Bosco, Eva Johansson, David Robinson, Lars Holmberg, Par Stattin, Mieke Van Hemelrijck
Journal: European Urology (2018)
2018 ACC Expert Consensus Decision Pathway on Tobacco Cessation Treatment
Authors: Rajat S. Barua, Nancy A. Rigotti, Neal L. Benowitz, K. Michael Cummings, Mohammad-Ali Jazayeri, Pamela B. Morris, Elizabeth V. Ratchford, Linda Sarna, Eric C. Stecker, Barbara S. Wiggins
Journal: Journal of the American College of Cardiology (2018)
CD38-Deficient, CD16-Engineered NK Cells Exhibit Enhanced Antibody-Dependent Cellular Cytotoxicity without NK Cell Fratricide to Augment Anti-Myeloma Immunity in Combination with Daratumumab
Authors: Karrune Woan, Ryan Bjordahl, Frank Cichocki, Svetlana Gaidarova, Cameron Pride, Dan S Kaufman, Karl-Johan Malmberg, Sarah Cooley, Bahram Valamehr, Jeffrey S. Miller
Journal: Blood (2018)
Chronic Calmodulin-Kinase II Activation Drives Disease Progression in Mutation-Specific Hypertrophic Cardiomyopathy
Authors: Sarah J. Lehman, Lauren Tal-Grinspan, Melissa L. Lynn, Joshua Strom, Grace E. Benitez, Mark E. Anderson, Jil C. Tardiff
Journal: Circulation (2019)

Although the genetic causes of hypertrophic cardiomyopathy (HCM) are widely recognized, considerable lag in the development of targeted therapeutics has limited interventions to symptom palliation. This is in part attributable to an incomplete understanding of how point mutations trigger pathogenic remodeling. As a further complication, similar mutations within sarcomeric genes can result in differential disease severity, highlighting the need to understand the mechanism of progression at the molecular level. One pathway commonly linked to HCM progression is calcium homeostasis dysregulation, though how specific mutations disrupt calcium homeostasis remains unclear.
The association between early‐onset cardiac events caused by neoadjuvant or adjuvant chemotherapy in triple‐negative breast cancer patients and some novel autophagy‐related polymorphisms in their genomic DNA: a real‐world study
Authors: Binliang Liu, Tao An, Meiying Li, Zongbi Yi, Chunxiao Li, Xiaoying Sun, Xiuwen Guan, Lixi Li, Yanfeng Wang, Yuhui Zhang, Binghe Xu, Fei Ma, Yixin Zeng
Journal: Cancer Communications (2018)

Abstract Background An increasing number of cancer patients die of cardiovascular diseases. The cardiotoxicity of chemotherapy is particularly important in triple‐negative breast cancer (TNBC) with limited therapeutic options. Cardiac autophagy is an important mechanism of cardiotoxicity. This research was aimed to investigate the cardiotoxicity of chemotherapy in TNBC, screen the susceptible population, and determine the relationship between cardiotoxicity and autophagy‐related polymorphisms. Methods From a total of 2450 stage I‐III TNBC patients, 147 met the inclusion criteria and finally recruited. Electrocardiography (ECG) was performed before most chemotherapy cycles, and echocardiography (UCG) was performed according to clinical needs. All ECG and UCG records were re‐interpreted by cardiologists at the National Center for Cardiovascular Disease, Fuwai Hospital. According to the National Center for Biotechnology Information and the Catalog of Somatic Mutations in Cancer database, we selected 25 single nucleotide polymorphisms (SNPs) related to autophagy and genotyped the 147 TNBC patients. Paired‐sample T tests, Chi squared tests, and logistic regression models were employed for the analysis. Results Only 46 (31.3%) patients had normal ECG records after every chemotherapy cycle. Among the 16 patients who underwent UCG, 2 (12.5%) had a reversible decrease of left ventricular ejection fraction. The use of anthracyclines and excessive alcohol consumption were risk factors of ECG abnormalities. With the continuation of chemotherapy, heart rate gradually increased. Anthracyclines were associated with QRS duration abnormalities ( P = 0.043). After genotyping for 25 autophagy‐related SNPs, we found that the G allele of autophagy‐related 13 ( ATG13 ) rs10838611 was significantly associated with ECG abnormalities (odds ratio = 2.258, 95% confidence interval = 1.318–3.869; P = 0.003). Conclusion ECG abnormalities caused by chemotherapy are common in the real world. Autophagy‐related SNPs are associated with chemotherapy‐induced cardiotoxicity, thereby providing new evidence for autophagy as a cause of chemotherapy‐induced cardiac damage.
Preclinical Activity of Novel MCL1 Inhibitor AZD5991 in Multiple Myeloma
Authors: Shannon M Matulis, Vikas A. Gupta, Izabelle Brown, Jonathan J Keats, Paul Secrist, Justin Cidado, Adriana E. Tron, Paola Neri, Nizar Bahlis, Jonathan L Kaufman, Leonard Heffner, Sagar Lonial, Ajay K Nooka, Lawrence H. Boise
Journal: Blood (2018)
SP0132 Measuring digital health literacy, why and how?
Authors: C. Drossaert
Journal: Annals of the Rheumatic Diseases (2018)

<h3></h3> Digital health literacy or eHealth Literacy refers to a person's ability to search, select, appraise and apply online health information or appropriately use digital health applications. In this presentation I will address the issue of measurement of these skills. First, we will explore why it is important to measure digital health literacy and discuss the different aims of measuring. Second, we will address some of the currently available instruments, including the oldest and most used instrument, the eHealth Literacy Scale or EHEALS Norman &amp; Skinner, 2006 and some more recent instruments, including the eHealth Literacy Questionnaire, eHLQ Kayser et al. 2018 and the Digital Health Literacy Instrument, DHLI. Van der Vaart &amp; Drossaert, 2017. Of each instrument, I will briefly discuss its underlying theory, some empirical findings, and its strengths and weaknesses. I will conclude with discussing some general challenges in measuring digital health literacy and directions for future research. <h3>Disclosure of Interest</h3> None declared
What Role Should Psychiatrists Have in Responding to the Opioid Epidemic?
Authors: Srinivas B. Muvvala, Ellen Lockard Edens, Ismene L. Petrakis
Journal: JAMA Psychiatry (2018)

This Viewpoint expresses concerns about the workforce available to care for patients with opioid use disorders and advises that psychiatrists become trained in the administration of buprenorphine and acquire other skills.
AB0100 Neurogenic inflammation characterised by nerve growth factor, trka and substance p is prevalent in human facet joint osteoarthritis
Authors: M.F. Seidel, J. Geurts, N. Busso, V. Chobaz, T. Hügle
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Facet joint osteoarthritis (FOA) is a frequent cause of chronic low back pain and spinal stenosis. Neuron-derived molecules regulate pain sensation and inflammation. Nerve growth factor (NGF) is one of the most important mediators for this mechanism that is termed neurogenic inflammation.<sup>1</sup> Among many other effects, it regulates substance P (SP) expression as pivotal downstream peripheral pro-inflammatory molecule. Consequently, NGF inhibitors (NGFi) as a novel class of pain medication have shown significant efficacy in OA and to some extent also low back pain. However, it is unknown which tissue compartments in facet joints are involved in NGF signalling. <h3>Objectives</h3> To determine expression patterns of NGF, its high affinity transmembrane tyrosine kinase A (TrkA) receptor and SP in cartilage, subchondral bone marrow and capsular tissues of facet joints (FJ). <h3>Methods</h3> Dissected human FOA specimens of six donors were examined. OA severity was graded on HE-stained tissue sections. NGF, TrkA and SP expression was evaluated by immunohistochemistry with monoclonal antibodies. Similarly, new bone formation was assessed by staining for osteocalcin. <h3>Results</h3> FJ had low (n=2), high (n=2) and intermediate (n=2) inflammatory bone marrow infiltrates. NGF was strongly expressed in capsular tissue (figure, 40x), focally in degenerated cartilage and differentially in FJ with active bone marrow infiltrates. TrkA was primarily found in all bone marrows and capsular tissues but not in cartilage. TrkA expression colocalized with osteocalcin in subchondral bone, indicating an association with new bone formation. SP strongly positive cells were found in the bone marrow, cartilage and synovial tissue of all FJ. <h3>Conclusions</h3> Here we define for the first time tissue compartments of the NGF axis in human FOA. The findings indicate that neurogenic inflammation is prevalent in different compartments of FOA. Based on these data NGFi might be efficient by targeting inflamed joint capsule or subchondral bone marrow as a source of pain. NGFi may thus have an impact on bone remodelling. Further studies are needed to more precisely examine this mechanism. <h3>References</h3> [1] Seidel MF, Herguijuela M, Forkert R, Otten U. Nerve growth factor in rheumatic diseases. Semin Arthritis Rheum. 2010;40(2):109–26. [2] Netzer C, Urech K, Hügle T, Benz RM, Geurts J, Schären S. Characterization of subchondral bone histopathology of facet joint osteoarthritis in lumbar spinal stenosis. J Orthop Res. 2016;34(8):1475–80. <h3>Disclosure of Interest</h3> None declared
Abstract 11582: Intercellular Transfer of Mir-126-3p by Endothelial Microparticles Reduces Vascular Smooth Muscle Cell Proliferation and Limits Neointima Formation by Inhibiting Lrp6
Authors: Feilx Jansen, Tobias Stumpf, Georg Nickenig, Nikos Werner
Journal: Circulation (2015)

Background: Vascular smooth muscle cell (VSMC) proliferation is of importance in the pathogenesis of vascular diseases such as restenosis or atherosclerosis. Endothelial microparticles (EMP) regulate function and phenotype of target endothelial cells (ECs), but their influence on VSMC biology is unknown. Hypothesis: Intercellular communication between ECs and VSMCs via EMPs regulates vascular remodelling. Methods and results: Systemic treatment of mice with EMPs after vascular injury reduced neointima formation in vivo. In vitro, EMP uptake in VSMCs diminished VSMC proliferation and migration, both pivotal steps in neointima formation. To explore the underlying mechanisms, Taqman microRNA-array was performed and microRNA (miR)-126-3p was identified as the predominantly expressed miR in EMP. Confocal microscopy revealed an EMP-mediated miR-126 transfer into recipient VSMCs. Expression of miR-126 target protein LRP6, regulating VSMC proliferation, was reduced in VSMCs after EMP treatment. Importantly, genetic regulation of miR-126 in EMPs showed a miR-126-dependent inhibition of LRP6 expression, VSMC proliferation and neointima formation in vitro and in vivo, suggesting a crucial role of miR-126 in EMP-mediated neointima formation reduction. Exposure of endothelial cells to pathological hyperglycaemic conditions prior to EMP release abrogated EMP-promoted neointima formation reduction. Finally, analysis of miR-126 expression in circulating MPs in 176 patients with coronary artery disease revealed a reduced PCI rate in patients with high miR-126 expression level, supporting a central role for MP-incorporated miR-126 in vascular remodelling. Conclusions: EMPs reduce VSMC proliferation, migration and subsequent neointima formation by delivering functional miR-126 into recipient VSMCs.
Toxicity following palliative radiation therapy for painful metastatic bone lesions.
Authors: Mikayla Jenkins, Mark Raymond Waddle, Tasneem Kaleem, William C Stross, Timothy D Malouff, Matthew DeVries, Delaney Pacitti, Jackson May, Aditya Patibandla, Launia White, Aaron Spaulding, James Naessens, Robert Clell Miller
Journal: Journal of Clinical Oncology (2018)

126 Background: Palliative radiation treatment (pRT) is a common and effective treatment for patients with symptomatic bone metastases. However, patients receiving RT for bone metastases often may have a poor performance status and are more likely to experience toxicity during or after treatment. This study aims to investigate the number and type of toxicity event occurring during or after pRT for bone metastases. Methods: Patients treated with RT for bone metastases at Mayo Clinic from 2007 to 2016 were included in this study. Demographic, disease, treatment, and toxicity information were collected. Specifically, toxicity events were identified as emergency department (ED) visits and inpatient hospitalization (IH) within 90 days, breaks in treatment &gt;4 days, and excessive 30 day financial toxicity defined as standardized Medicare costs &gt;1 standard deviation above the mean. RT treatment was compared by dose and fractionation via descriptive statistics. Results: A total of 538 patients treated with pRT were identified, 124 receiving 8Gy x1, 204 receiving 4Gy x5, and 210 receiving 3Gy x10. Patients with breast and prostate cancer were most likely to be treated with 3Gy x10 and patients with GI and Lung cancer were most likely to be treated with 8Gy x1. A description of the patient characteristics and toxicities are shown in Table 1. For 8Gy x1, 4Gy x5, and 3Gy x10 breaks in treatment were rare (0%, 2%, and 3.3%), ED visits (15%, 24%, &amp; 28%), IH (12%, 23%, &amp; 19%), and financial toxicity (13%, 18%, &amp; 21%) were common. A total of 22.6%, 27.5%, and 38.6% of patients were alive two years following pRT from each group. Conclusions: Toxicity during or shortly after pRT of bone metastases is common. This study confirms that additional steps should be taken to monitor and mitigate toxicity in this vulnerable patient group. [Table: see text]
FRI0475 Lung damage in patients with microscopic polyangiitis
Authors: E. Shchegoleva, A. Zykova, N. Bulanov, A. Meshkov, P. Novikov, S. Moiseev
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Objectives</h3> We evaluated the frequency of clinical and CT features of lung damage in patients with microscopic polyangiitis (MPA). <h3>Methods</h3> We enrolled 97 patients with MPA, that was diagnosed according to CHCC2012. The median age at disease onset was 50.7±16.6 (M±SEM) years, the median duration of follow-up was 47.6±47.5 (M±SEM) months. 64 (66.0%) patients were ANCA-MPO-positive, 24 patients (24.7%) were ANCA-PR-3-positive, and 9 (9.3%) patients had undifferentiated ANCA. Diffuse alveolar haemorrhage (DAH) was diagnosed by the presence of dyspnea, hemoptysis, anaemia and pulmonary infiltrates on chest CT. <h3>Results</h3> Lung damage was diagnosed in 77 (79.4%) patients. 43 (55.8%) patients had pulmonary damage at the disease onset, while 34 (44.2%) patients developed signs of lung involvement within 8.0±4.1 (M±SEM) months. At baseline, the median pulmonary BVAS was 4.<sup>2; 6</sup> The interstitial changes occurred in more than half of cases at the onset of the disease. The most frequent CT-patterns included pulmonary infiltrates (n=49) and ground-glass opacity (n=39) (table 1). DAH developed in 30 (30.9%) patients, among them 15 (15.5%) had DAH at the onset of the disease. The pulmonary fibrosis was the most common CT-pattern at the end of follow-up (52 patients). Notably, interstitial damages at the onset of disease were associated with the development of fibrotic changes (OR=4.7, 95% CI 1.7–12.9) and bronchiectasis (OR=9.8, 95% CI 1.2–78.3) at the end of follow-up. The median of pulmonary VDI was 1 (0;4) at the end of the follow up. PR-3-positive group had higher occurrence of consolidations at the end of the follow-up as compared to patients with anti-MPO-antibodies (53.8% versus 16.0%, p=0.023). The pulmonary fibrosis was the most common CT-pattern at the end of follow-up (52 patients). Notably, interstitial damages at the onset of disease were associated with the development of fibrotic changes (OR=4.7, 95% CI 1.7–12.9) and bronchiectasis (OR=9.8, 95% CI 1.2–78.3) at the end of follow-up. The median of pulmonary VDI was 1 (0;4) at the end of the follow up. PR-3-positive group had higher occurrence of consolidations at the end of the follow-up as compared to patients with anti-MPO-antibodies (53.8% versus 16.0%, p=0.023). <h3>Conclusions</h3> In patients with MPA, the CT signs of interstitial damage were usually reversible. However, they predicted a higher incidence of lung fibrosis and bronchiectasis at the end of follow-up. DAH occured in one third of patients with MPA. <h3>Disclosure of Interest</h3> None declared
Ebola and War in the Democratic Republic of Congo
Authors: Lawrence O. Gostin, Matthew M. Kavanagh, Elizabeth Cameron
Journal: JAMA (2018)

In this Viewpoint, Gostin and colleagues review recommendations developed by experts convened by Georgetown University on how the international community can respond to the 2018 Ebola outbreak in the Democratic Republic of Congo (DRC) in the midst of active conflict and insecurity from armed rebels.