tbuckley/cabot-search huggingface dataset:
Immediate bronchodilator response in FEV<sub>1</sub>as a diagnostic criterion for adult asthma
Authors: Leena E. Tuomisto, Pinja Ilmarinen, Lauri Lehtimäki, Minna Tommola, Hannu Kankaanranta
Journal: European Respiratory Journal (2018)

Asthma is characterised by variable and reversible expiratory airflow limitations. Thus, it is logical to use the change in forced expiratory volume in 1 s (FEV 1 ) in response to a bronchodilator (ΔFEV 1 BDR) as a diagnostic tool; increases of ≥12% and ≥200 mL from the baseline FEV 1 are commonly used values. We aimed to evaluate the historical development of diagnostic cut-off levels for the ΔFEV 1 BDR for adults and the evidence behind these recommendations. We searched for studies from the reference lists of all the main statements, reports and guidelines concerning the interpretation of spirometry and diagnostics for asthma and conducted a literature search. A limited amount of evidence regarding the ΔFEV 1 BDR in healthy populations was found, and even fewer patient studies were found. In healthy persons, the upper 95th percentile for the absolute ΔFEV 1 BDR ranges between 240 mL and 320 mL, the relative ΔFEV 1 BDR calculated from the initial FEV 1 ranges from 5.9% to 13.3% and the ΔFEV 1 BDR calculated from the predicted FEV 1 ranges from 8.7% to 11.6%. However, the absolute and percentage ΔFEV 1 BDR values calculated from the initial FEV 1 are dependent on age, sex, height and the degree of airway obstruction. Thus, the use of the ΔFEV 1 BDR calculated from the predicted FEV 1 might be more appropriate. Not enough data exist to assess the sensitivity of any of the cut-off levels for the ΔFEV 1 BDR to differentiate asthma patients from healthy subjects. Further studies in newly diagnosed asthma patients are needed.
Abstract 18302: Therapeutic Optimization of Mesenchymal Stem Cells by Combinational Application With Primed Stem Cells in Myocardial Infarction Model
Authors: Dong Im Cho, Wan Seok Kang, Hye-jin Kang Kang, Yong Sook Kim, Youngkeun Ahn
Journal: Circulation (2016)

Introduction: We have already confirmed that mesenchymal stem cells (MSCs) were highly cardiogenically modified by treatment with compound A (CompA) for 24 hours, and one of critical regulators was...
Abstract 24047: G Protein-coupled Receptor Kinase 2 Negatively Regulates Fatty Acid Utilization and Mitochondrial Bioenergetics
Authors: Jessica M Pfleger, Walter J Koch
Journal: Circulation (2017)

During cardiac injury or stress, G protein-coupled receptor (GPCR) kinase 2 (GRK2) expression levels and activity are increased, leading to a desensitization of myocardial β-adrenergic receptors (βARs) and contributing to the loss of contractile reserve. Up-regulated GRK2 has been shown to be pathogenic in the post-injured heart and is involved in the promotion of heart failure (HF). There is evidence that GRK2 has other, non-GPCR dependent pathological functions within cardiomyocytes. For example, GRK2 localizes to the mitochondria following oxidative stress, where it acts as a pro-death kinase and decreases fatty acid utilization. As metabolic substrate utilization and bioenergetics are key parameters in the maintenance of cardiomyocyte contractility, our objective is to examine the role of GRK2 on metabolism and bioenergetics in the adult heart. We hypothesize that desensitization of βARs via an increase in GRK2 will result in decreased fatty acid-fueled respiration and will compromise cardiomyocyte function. Conversely, ablation of GRK2 will result in increased respiration and function, under these conditions. Our results show that basal respiration, maximal respiration, and reserve respiratory capacity (RRC) are highest in the presence of palmitate versus glucose (1.6, 3, and 7.2-fold, respectively), accompanied by increased (1.3-fold) ATP levels. Moreover, basal and maximal respiration was decreased (1.6 and 1.2-fold, respectively) cardiomyocytes isolated from cardiac-specific GRK2 transgenic mice. This correlates with a decrease in ATP levels and in vivo cardiac fatty acid uptake (1-fold and 1.6-fold, respectively). Conversely, cardiomyocytes isolated from βARKct, a peptide inhibitor of GRK2, transgenic mice or GRK2 knockout mice, show increased maximal respiration (1.5 and 1.4-fold, respectively) and RRC (2.7 and 2.2-fold, respectively) with fatty acids. This correlates with an increase in ATP levels (1.2-1.9-fold). Thus, we propose that increased GRK2, as seen during heart failure, compromises fatty acid-driven mitochondrial respiration, while GRK2 inhibition under these conditions enhances RRC, which is known to improve cellular survival during stress.
AB0061 Serum il-37 as an efficient biomarker of disease activity in patients with ankylosing spondylitis: post-hoc analysis of planetas study
Authors: G.Y. Ahn, S. Kang, B. Nam, J.S. Kim, J. Kang, D.-H. Yoo
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> IL-37 is an anti-inflammatory cytokine which belongs to IL-1 cytokine superfamily. Patients with ankylosing spondylitis (AS) also had a higher serum IL-37 concentration than controls, and were also associated with other inflammatory markers such as CRP, ESR, and BASDAI levels.<sup>1</sup> However, the relationship between serum IL-37 and disease activity after anti-TNF treatment has not been reported. <h3>Objectives</h3> To investigate the association of serum IL-37 level with disease activity in AS patients who were treated with infliximab. <h3>Methods</h3> Patients were recruited from the PLANETAS study (NCT01220518). Patients with active AS were treated with CT-P13 or infliximab originator. The serum levels of IL-37 were measured at week 0 and week 30 with specific ELISA. Other demographic, laboratory and clinical variables were evaluated simultaneously. <h3>Results</h3> Fifty patients with active AS (BASDAI &gt;4) were analysed. The median age of patients was 40 years old [Interquartile range (IQR), 33.8–49.5), and the median BASDAI score was 6.7 (IQR 5.3–7.9). Compared to baseline, all measured clinical and laboratory parameters and serum IL-37 were significantly reduced. There was a statistically significant correlation between IL-37 and CRP, BASDAI at baseline, but not at week 30. Additionally, the differences (Δ) of parameters at baseline and at week 30 were assessed on their associations with other disease activity parameters. Delta IL-37 was significantly correlated with ΔCRP, ΔBASFI and ΔBASDAI. The ROC curves of serum biomarkers for ASAS 20 achievement revealed that AUC value for ΔIL-37 (AUC=0.74) was similar with ΔESR (AUC=0.71, p=0.64) and superior than ΔCRP (AUC=0.54, p&lt;0.01). AUC value for ΔIL-37 of ASAS 40 achievement was 0.66, which was similar with ΔESR (AUC=0.60, p=0.38) and superior than ΔCRP (0.46, p&lt;0.01). <h3>Conclusions</h3> Serum IL-37 levels are associated with BASDAI, patient's pain score, and CRP in active AS patients. Change in serum IL-37 level may serve as an efficient biomarker predicting the improvement of BASDAI and the achievement of ASAS 20 and 40 after anti-TNF treatment in AS patients. <h3>Reference</h3> [1] Chen B, Huang K, Ye L, et al. Interleukin-37 is increased in ankylosing spondylitis patients and associated with disease activity. J Transl Med2015;13:36. <h3>Disclosure of Interest</h3> None declared
Breast Cancer Screening and Diagnosis, Version 3.2018, NCCN Clinical Practice Guidelines in Oncology
Authors: Therese B. Bevers, Mark Helvie, Ermelinda Bonaccio, Kristine E. Calhoun, Mary B. Daly, William B. Farrar, Judy E. Garber, Richard Gray, Caprice C. Greenberg, Rachel Greenup, Nora M. Hansen, Randall E. Harris, Alexandra S. Heerdt, Teresa Helsten, Linda Hodgkiss, Tamarya L. Hoyt, John G. Huff, Lisa Jacobs, Constance Dobbins Lehman, Barbara Monsees, Bethany L. Niell, Catherine C. Parker, Mark Pearlman, Liane Philpotts, Laura B. Shepardson, Mary Lou Smith, Matthew Stein, Lusine Tumyan, Cheryl Williams, Mary Anne Bergman, Rashmi Kumar
Journal: Journal of the National Comprehensive Cancer Network (2018)

The NCCN Guidelines for Breast Cancer Screening and Diagnosis have been developed to facilitate clinical decision making. This manuscript discusses the diagnostic evaluation of individuals with suspected breast cancer due to either abnormal imaging and/or physical findings. For breast cancer screening recommendations, please see the full guidelines on NCCN.org.
E3611—A Randomized Phase II Study of Ipilimumab at 3 or 10 mg/kg Alone or in Combination with High-Dose Interferon-α2b in Advanced Melanoma
Authors: Ahmad A. Tarhini, Sandra J. Lee, Xiaoxue Li, Uma N.M. Rao, Arun Nagarajan, Mark R. Albertini, Jerry W. Mitchell, Stuart J. Wong, Mark A. Taylor, Noel Laudi, Phu V. Truong, Robert M. Conry, John M. Kirkwood
Journal: Clinical Cancer Research (2018)

Interferon-α favors a Th1 shift in immunity, and combining with ipilimumab (ipi) at 3 or 10 mg/kg may downregulate CTLA4-mediated suppressive effects, leading to more durable antitumor immune responses. A study of tremelimumab and high-dose interferon-α (HDI) showed promising efficacy, supporting this hypothesis.
Quality of life in the CHISEL randomized trial of stereotactic ablative radiotherapy (SABR) versus standard radiotherapy for stage I non-small cell lung cancer (Trans-Tasman Radiation Oncology Group 09.02)
Authors: D. Ball, G.T. Mai, S. Vinod, S. Babington, J. Ruben, T. Kron, B. Chesson, A. Herschtal, M. Vanevski, A. Rezo, C. Elder, M. Skala, A. Wirth, G. Wheeler, A. Lim, M. Shaw, P. Schofield, L. Irving, B. Solomon
Journal: Annals of Oncology (2018)
Next generation flow for minimally-invasive blood characterization of MGUS and multiple myeloma at diagnosis based on circulating tumor plasma cells (CTPC)
Authors: L. Sanoja-Flores, J. Flores-Montero, J. J. Garcés, B. Paiva, N. Puig, A. García-Mateo, O. García-Sánchez, A. Corral-Mateos, L. Burgos, E. Blanco, J. Hernández-Martín, R. Pontes, M. Díez-Campelo, P. Millacoy, P. Rodríguez-Otero, F. Prosper, J. Merino, M. B. Vidriales, R. García-Sanz, A. Romero, L. Palomera, R. Ríos-Tamayo, M. Pérez-Andrés, J. F. Blanco, M. González, J. J. M. van Dongen, B. Durie, M. V. Mateos, J. San-Miguel, A. Orfao
Journal: Blood Cancer Journal (2018)

Here, we investigated for the first time the frequency and number of circulating tumor plasma cells (CTPC) in peripheral blood (PB) of newly diagnosed patients with localized and systemic plasma cell neoplasms (PCN) using next-generation flow cytometry (NGF) and correlated our findings with the distinct diagnostic and prognostic categories of the disease. Overall, 508 samples from 264 newly diagnosed PCN patients, were studied. CTPC were detected in PB of all active multiple myeloma (MM; 100%), and smoldering MM (SMM) patients (100%), and in more than half (59%) monoclonal gammopathy of undetermined significance (MGUS) cases (p <0.0001); in contrast, CTPC were present in a small fraction of solitary plasmacytoma patients (18%). Higher numbers of CTPC in PB were associated with higher levels of BM infiltration and more adverse prognostic features, together with shorter time to progression from MGUS to MM (p <0.0001) and a shorter survival in MM patients with active disease requiring treatment (p ≤ 0.03). In summary, the presence of CTPC in PB as assessed by NGF at diagnosis, emerges as a hallmark of disseminated PCN, higher numbers of PB CTPC being strongly associated with a malignant disease behavior and a poorer outcome of both MGUS and MM.
Stroke Risk Stratification for Atrial Fibrillation Patients With Hypertrophic Cardiomyopathy
Authors: Hyunjean Jung, Jung-Hoon Sung, Pil-Sung Yang, Eunsun Jang, Hee Tae Yu, Tae-Hoon Kim, Hui-Nam Pak, Moon-Hyoung Lee, Boyoung Joung, Gregory Y.H. Lip
Journal: Journal of the American College of Cardiology (2018)
Cerebral cavernous malformations form an anticoagulant vascular domain in humans and mice
Authors: Miguel Alejandro Lopez-Ramirez, Angela Pham, Romuald Girard, Tine Wyseure, Preston Hale, Atsuki Yamashita, Janne Koskimäki, Sean Polster, Laleh Saadat, Ignacio A. Romero, Charles T. Esmon, Frederic Lagarrigue, Issam A. Awad, Laurent O. Mosnier, Mark H. Ginsberg
Journal: Blood (2018)
Margaret Becklake: internationally renowned epidemiologist and respiratory medicine specialist
Authors: Barbara Kermode-Scott
Journal: BMJ (2018)

Margot Becklake



Margaret Becklake (mostly known as Margot) dedicated six decades of her life to ensuring that others could breathe easily. She undertook international research in respiratory medicine, with a special interest in the host, environmental, and occupational determinants of childhood, and in adult airway disease. A fearless advocate for workers, she witnessed and documented the impact of asbestos, smoke, and all kinds of dust (especially in coal and gold mines and grain mills) on respiratory health in Canada, Kenya, and South Africa. Throughout her career, Becklake employed epidemiology as a tool for change and for protecting the public. She successfully challenged existing clinical dogma and worked hard to improve the lives of workers on low incomes. Remembered as a “voice of eminence and reason,”1 she became a highly respected and well liked physician, researcher, teacher, and mentor.

Born in Edmonton, Middlesex, in 1922, to James Becklake and Dorothy Mills, Becklake was raised in Pretoria in South Africa as her father was appointed …
Genomic Evidence of Local Adaptation to Climate and Diet in Indigenous Siberians
Authors: Brian Hallmark, Tatiana M Karafet, PingHsun Hsieh, Ludmila P Osipova, Joseph C Watkins, Michael F Hammer
Journal: Molecular Biology and Evolution (2018)

The indigenous inhabitants of Siberia live in some of the harshest environments on earth, experiencing extended periods of severe cold temperatures, dramatic variation in photoperiod, and limited and highly variable food resources. While the successful long-term settlement of this area by humans required multiple behavioral and cultural innovations, the nature of the underlying genetic changes has generally remained elusive. In this study, we used a three-part approach to identify putative targets of positive natural selection in Siberians. We first performed selection scans on whole exome and genome-wide single nucleotide polymorphism array data from multiple Siberian populations. We then annotated candidates in the tails of the empirical distributions, focusing on candidates with evidence linking them to biological processes and phenotypes previously identified as relevant to adaptation in circumpolar groups. The top candidates were then genotyped in additional populations to determine their spatial allele frequency distributions and associations with climate variables. Our analysis reveals missense mutations in three genes involved in lipid metabolism (PLA2G2A, PLIN1, and ANGPTL8) that exhibit genomic and spatial patterns consistent with selection for cold climate and/or diet. These variants are unified by their connection to brown adipose tissue and may help to explain previously observed physiological differences in Siberians such as low serum lipid levels and increased basal metabolic rate. These results support the hypothesis that indigenous Siberians have genetically adapted to their local environment by selection on multiple genes.
Will your patient benefit from palliative care? A multicenter exploratory survey about the acceptance of trigger factors for palliative care consultations among ICU physicians
Authors: Kathrin Adler, Daniel Schlieper, Detlef Kindgen-Milles, Stefan Meier, Manuela Schallenburger, Timur Sellmann, Heidrun Schwager, Jacqueline Schwartz, Martin Neukirchen
Journal: Intensive Care Medicine (2018)
A comparison of two biological markers of recent hepatitis C virus (HCV) infection: implications for the monitoring of interventions and strategies to reduce HCV transmission among people who inject drugs
Authors: Vivian D Hope, Ross J Harris, Peter Vickerman, Lucy Platt, Justin Shute, Katelyn J Cullen, Samreen Ijaz, Sema Mandal, Fortune Ncube, Monica Desai, John V Parry
Journal: Eurosurveillance (2018)

Background Monitoring hepatitis C virus (HCV) incidence is important for assessing intervention impact. Longitudinal studies of people who inject drugs (PWID), using repeated biological tests, are costly; alternatively, incidence can be estimated using biological markers of recent infection in cross-sectional studies. Aim We aimed to compare incidence estimates obtained from two different biological markers of recent infection in a cross-sectional study to inform monitoring approaches for HCV elimination strategies. Method Samples from an unlinked anonymous bio-behavioural survey of PWID were tested for two recent infection markers: HCV RNA with anti-HCV negative (‘RNA’) and low-avidity anti-HCV with HCV RNA present (‘avidity’). These two markers were used separately and in combination to estimate HCV incidence. Results Between 2011 and 2013, 2,816 anti-HIV-negative PWID (25% female) who had injected during the preceding year were either HCV-negative or had one of the two markers of recent infection: 57 (2.0%) had the RNA marker and 90 (3.2%) the avidity marker. The two markers had similar distributions of risk and demographic factors. Pooled estimated incidence was 12.3 per 100 person-years (pyrs) (95% credible interval: 8.8–17.0) and not significantly different to avidity-only (p = 0.865) and RNA-only (p = 0.691) estimates. However, the RNA marker is limited by its short duration before anti-HCV seroconversion and the avidity marker by uncertainty around its duration. Conclusion Both markers have utility in monitoring HCV incidence among PWID. When HCV transmission is high, one marker may provide an accurate estimate of incidence; when it is low or decreasing, a combination may be required.
Hemifacial Hyperhidrosis in a Patient With an Apical Non–Small Cell Lung Cancer
Authors: Lindsey Sloan, Carlos G. Romo, Russell Kenneth Hales
Journal: JAMA Oncology (2018)

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Erythromycin versus metoclopramide for post-pyloric spiral nasoenteric tube placement: a randomized non-inferiority trial
Authors: Bei Hu, Xin Ouyang, Liming Lei, Cheng Sun, Ruibin Chi, Jian Guo, Wenlong Guo, Yanlin Zhang, Yong Li, Daoyong Huang, Huafeng Sun, Zhiqiang Nie, Jieyang Yu, Yuan Zhou, Hao Wang, Jinhe Zhang, Chunbo Chen
Journal: Intensive Care Medicine (2018)

To determine whether erythromycin is non-inferior to metoclopramide in facilitating post-pyloric placement of self-propelled spiral nasoenteric tubes (NETs) in critically ill patients. A prospective, multicenter, open-label, parallel, and non-inferiority randomized controlled trial was conducted comparing erythromycin with metoclopramide in facilitating post-pyloric placement of spiral NETs in critically ill patients admitted to intensive care units (ICUs) of eight tertiary hospitals in China. The primary outcome was procedure success defined as post-pyloric placement (spiral NETs reached the first portion of the duodenum or beyond confirmed by abdominal radiography 24 h after tube insertion). A total of 5688 patients were admitted to the ICUs. Of these, in 355 patients there was a plan to insert a nasoenteric feeding tube, of whom 332 were randomized, with 167 patients assigned to the erythromycin group and 165 patients assigned to the metoclopramide group. The success rate of post-pyloric placement was 57.5% (96/167) in the erythromycin group, as compared with 50.3% (83/165) in the metoclopramide group (a difference of 7.2%, 95% CI − 3.5% to 17.9%), in the intention-to-treat analysis, not including the prespecified margin of − 10% for non-inferiority. The success rates of post-D1 (reaching the second portion of the duodenum or beyond), post-D2 (reaching the third portion of the duodenum or beyond), post-D3 (reaching the fourth portion of the duodenum or beyond), and proximal jejunum placement and the incidence of any adverse events were not significantly different between the groups. Erythromycin is non-inferior to metoclopramide in facilitating post-pyloric placement of spiral NETs in critically ill patients. The success rates of post-D1, post-D2, post-D3, and proximal jejunum placement were not significantly different.
SAT0605 The presence of uveitis predicts the response to the interleukin (IL)-1 inhibitors anakinra and canakinumab in behÇet’s disease
Authors: C. Fabiani, A. Vitale, G. Emmi, G. Lopalco, D. Rigante, J. Sota, I. Orlando, B. Frediani, R. Franceschini, M. Galeazzi, F. Iannone, G.M. Tosi, L. Cantarini
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> In recent times IL-1 inhibition has been proposed as an intriguing therapeutic option in Behçet disease (BD) patients with multi-drug resistant manifestations.<sup>1</sup> However, despite the good clinical results obtained during the last years, cases of BD nonresponsive to anakinra (ANA) and canakinumab (CAN) have also been identified. This evidence has induced to suspect the existence of specific subsets of patients characterised by a more pronounced IL-1 driven pathogenesis.<sup>2,3</sup> <h3>Objectives</h3> To identify predictive factors of response to interleukin (IL)−1 inhibition among demographic, clinical and therapeutic data in patients with (BD). <h3>Methods</h3> BD patients treated with ANA or CAN were enrolled. Patients were divided into 2 groups according to the clinical response: group 1 included subjects showing a treatment duration of at least 52 weeks and no secondary inefficacy during the first follow-up year; the remaining patients were included in the group 2. Demographic, clinical and therapeutic data were analysed to identify significant differences between groups. <h3>Results</h3> Eighteen patients (50%) were included in group 1 and 18 (50%) in group 2. A better response to IL-1 inhibitors was significantly more common among patients with BD-related uveitis (p=0.006) and patients with a longer disease duration (p=0.03). <h3>Conclusions</h3> IL-1 blockade is effective in BD, especially in the subset of patients presenting ocular involvement and in those with long-lasting disease. <h3>References</h3> [1] Vitale A, Rigante D, Lopalco G, Selmi C, Galeazzi M, Iannone F, Cantarini L. Interleukin-1 inhibition in Behçet's disease. Isr Med Assoc J2016;18(3–4):171–6. [2] Vitale A, Rigante D, Caso F, Brizi MG, Galeazzi M, Costa L, et al. Inhibition of interleukin-1 by canakinumab as a successful mono-drug strategy for the treatment of refractory Behçet's disease: a case series. Dermatology2014;228(3):211–4. doi:10.1159/000358125 [3] Cantarini L, Vitale A, Scalini P, Dinarello CA, Rigante D, Franceschini R, et al. Anakinra treatment in drug-resistant Behcet's disease: a case series. Clin Rheumatol2015;34(7):1293–301. doi:10.1007/s10067-013-2443-8 <h3>Disclosure of Interest</h3> None declared