tbuckley/cabot-search huggingface dataset:
AB1163 My behcet’s disease and my menstruation cycle: observation from an irish cohort
Authors: W.L. Ng, F. Adeeb, A. Sebastian, A. Anjum, M. Brady, M. Gillespie, F. Irwin, B. McCarthy, J. Devlin, A. Fraser
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> The menstrual cycle is regulated by the rise and fall of sex hormones in the body. Literature has demonstrated anti-inflammatory properties in both progesterone and oestrogen hormones.<sup>1</sup> There has been recent interest to determine the association between Behçet's Disease (BD), a poorly understood autoinflammatory disorder and menstruation. <h3>Objectives</h3> The objective of this study was to evaluate the effect of menstruation in triggering exacerbations of Behçet's disease in a Northern European cohort. <h3>Methods</h3> 18 female patients from our rheumatology department satisfying the International Study Group for Behçet's Disease (ISGBD) criteria were recruited. A questionnaire was conducted via telephone to determine whether their exacerbations of BD were correlated to their menstrual cycle. <h3>Results</h3> All 18 patients responded to the questionnaire, with the mean age of 38.8 years and mean age of menarche of 13 years. Four (22.22%) patients were in menopausal state. Half (nine) of the patients reported that their BD flare ups were correlated to their menstrual cycle. Exacerbations experienced include oral aphthosis (88.9%), arthralgia (55.6%), genital ulcerations (44.4%), lethargy (44.4%), skin lesions (11.1%) and headaches (11.1%). Six of the seven patients (86%) who were on contraception were on a progesterone containing contraception. Four out of nine (44%) who did not notice any exacerbations during menstruation stated that they were on progesterone containing contraceptives. It is noteworthy that 10 patients (55.56%) had previous pregnancies while three patients experienced an episode of miscarriage and 1 had a stillbirth. <h3>Conclusions</h3> Our results demonstrated that the disease activity in BD is related to the menstrual cycle, which is contributed by the female sex hormones. The study supports previous hypothesis that the abrupt decline in progesterone during onset of menstruation is associated to disease flare in BD.<sup>2</sup> Studies comprising larger cohorts should be conducted to further support and strengthen this evidence. <h3>References</h3> [1] Szekeres-Bartho J, Barakonyi A, Par G, et al. Progesterone as an immunomodulatory molecule. Int J Immunopharmacol. 2001; 1: 1037–48. [2] Bang D, Chun YS, Haam IB, et al. The influence of pregnancy on Behçet's disease. Yonsei Med J. 1997; 38: 437–43 <h3>Disclosure of Interest</h3> None declared
Drug Overdose Deaths Among Women Aged 30–64 Years — United States, 1999–2017
Authors: Jacob P. VanHouten, Rose A. Rudd, Michael F. Ballesteros, Karin A. Mack
Journal: MMWR Morbidity and Mortality Weekly Report (2019)

The drug epidemic in the United States continues to evolve. The drug overdose death rate has rapidly increased among women (1,2), although within this demographic group, the increase in overdose death risk is not uniform. From 1999 to 2010, the largest percentage changes in the rates of overall drug overdose deaths were among women in the age groups 45-54 years and 55-64 years (1); however, this finding does not take into account trends in specific drugs or consider changes in age group distributions in drug-specific overdose death rates. To target prevention strategies to address the epidemic among women in these age groups, CDC examined overdose death rates among women aged 30-64 years during 1999-2017, overall and by drug subcategories (antidepressants, benzodiazepines, cocaine, heroin, prescription opioids, and synthetic opioids, excluding methadone). Age distribution changes in drug-specific overdose death rates were calculated. Among women aged 30-64 years, the unadjusted drug overdose death rate increased 260%, from 6.7 deaths per 100,000 population (4,314 total drug overdose deaths) in 1999 to 24.3 (18,110) in 2017. The number and rate of deaths involving antidepressants, benzodiazepines, cocaine, heroin, and synthetic opioids each increased during this period. Prescription opioid-related deaths increased between 1999 and 2017 among women aged 30-64 years, with the largest increases among those aged 55-64 years. Interventions to address the rise in drug overdose deaths include implementing the CDC Guideline for Prescribing Opioids for Chronic Pain (3), reviewing records of controlled substance prescribing (e.g., prescription drug monitoring programs, health insurance programs), and developing capacity of drug use disorder treatments and linkage to care, especially for middle-aged women with drug use disorders.
SAT0333 Drug survival on first tnf inhibitors in patients with psoriatic arthritis: comparison across etanercept, adalimumab, golimumab and infliximab
Authors: C. García-Porrúa, F. Maceiras-Pan, L. Fernandez-Dominguez, J.A. Mosquera-Martinez, B. Correa-Rey, M. Pombo-Suarez, J. Pinto-Tasende
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> It is commonly accepted that additional methotrexate (MTX) does not increase efficacy for treatment with TNF in psoriatic arthritis (PsA) but concomitant MTX has been also associated with increased drug survival in register studies. However, the role of MTX comedication in PsA is still unclear. <h3>Objectives</h3> We aim was to evaluate TNF-α inhibitor (TNFi) persistence when used as first -line biologic therapy for the management of PsA naïve to biologic and determine features of patients as MTX comedication that are associated with TNFi persistence. <h3>Methods</h3> A ambispective longitudinal observational multi-centre cohort study was performed on all patients with PsA starting first TNFi therapy (etanercept, adalimumab, golimumab and infliximab) between 01/JUN/2003 and 01/12/2015. Demographic and clinical data, concomitant treatment with MTX, were compared with TNFi persistence, using Kaplan-Meier survival and Cox regression analysis. <h3>Results</h3> Were included 468 patients starting treatment with etanercept (242), adalimumab (120), golimumab<sup>31</sup> and infliximab (75); 235 receiving TNFi as monotherapy (50.2%) and 233 receiving concomitant MTX (49.8%). Mean age was 53.3±12.6 years (men 53.3±12.9 and women 53.2±12.3, p=0.928) and 55.2% were men. Obesity (BMI ≥30) was similar in patients with or without persistence on treatment: 30.39 (13.32) vs 29.20 (5.44), p=0.355). At 60 months of follow-up 50.6% of patients persisted with TNFi therapy (55.8% with etanercept, 50.0% with adalimumab, 29.3% with infliximab and 67.7% with golimumab). Infliximab had the lowest retention rate (p=0.006). Drug survival analyses had not differences between patients receiving co-medication or not (p=0.849). In the Cox regression analysis lack of concomitant MTX and gender female were predictors of discontinuation of TNFi (0.014). <h3>Conclusions</h3> At 60 months infliximab had the lowest percentage of treatment continuation compared with etanercept, adalimumab and golimumab. Patients with PsA who are female and have not concomitant treatment with MTX could have lower TNFi persistence. <h3>Reference</h3> [1] Fagerli KM, Lie E, van der Heijde D, et al. The role of methotrexate co-medication in TNF-inhibitor treatment in patients with psoriatic arthritis: results from 440 patients included in the NOR-DMARD study. Annals of the Rheumatic Diseases2014;73:132–137. <h3>Acknowledgements</h3> The authors are grateful for the support of the members of the Galician Society of Rheumatology (SOGARE) <h3>Disclosure of Interest</h3> None declared
A Single SNP Turns a Social Honey Bee (<i>Apis mellifera</i>) Worker into a Selfish Parasite
Authors: Denise Aumer, Eckart Stolle, Michael Allsopp, Fiona Mumoki, Christian W W Pirk, Robin F A Moritz
Journal: Molecular Biology and Evolution (2018)

The evolution of altruism in complex insect societies is arguably one of the major transitions in evolution and inclusive fitness theory plausibly explains why this is an evolutionary stable strategy. Yet, workers of the South African Cape honey bee (Apis mellifera capensis) can reverse to selfish behavior by becoming social parasites and parthenogenetically producing female offspring (thelytoky). Using a joint mapping and population genomics approach, in combination with a time-course transcript abundance dynamics analysis, we show that a single nucleotide polymorphism at the mapped thelytoky locus (Th) is associated with the iconic thelytokous phenotype. Th forms a linkage group with the ecdysis-triggering hormone receptor (Ethr) within a nonrecombining region under strong selection in the genome. A balanced detrimental allele system plausibly explains why the trait is specific to A. m. capensis and cannot easily establish itself into genomes of other honey bee subspecies.
A novel soluble single-chain T-cell receptor IgG1 fusion protein retains MHC restricted peptide specific antigen binding and exhibits anti-tumor effects in vivo.
Authors: Heather J. Belmont, Luis A. Mosquera, Kimberlyn F. Card, Shari A. Price-Schiavi, Janette Builes, Hing C. Wong
Journal: Cancer Research (2004)

2185  The therapeutic potential of tumor specific T cell receptor (TCR)-based immunotherapies has been suggested by reports that show tumor eradication, both in mice and in humans, can be mediated by CD8+ cytotoxic T lymphocytes (CTL). The TCR demonstrates exquisite specificity much like that of an antibody, and we have created high affinity soluble, single-chain TCR-based fusion proteins to be used as targeting agents for cancer therapies. Such TCR-based cancer therapies may significantly expand the target range of targeted therapies because TCRs recognize peptide epitopes derived from both intra-and extracellular proteins presented in the context of MHC, whereas antibodies only recognize antigens on extracellular proteins. To test the idea that high affinity scTCR-based fusion proteins have therapeutic utility, we have created a TCR that recognizes a distinct, naturally processed peptide fragment of the unmutated, human tumor suppressor protein, p53, presented on the cell surface in the context of HLA-A2. This soluble, single-chain TCR, which we call 264scTCR, was isolated from a p53 (aa 264-272) high avidity CTL clone derived from the HLA-A2.1 transgenic mice. To equip the 264scTCR with immunomodulatory functions, we have genetically linked it the immunomodulatory Fc domain of human IgG1 (264scTCR/IgG1). The 264scTCR should guide the immunomodulatory IgG1 Fc domain to tumors to trigger eradicatation of malignant cells. The TCR/IgG1 fusion protein has been expressed at high levels in mammalian cells. MHC restricted antigen specific binding properties are maintained in the single-chain, three domain TCR portion of this fusion protein, and the Fc domain is capable of Fc receptor binding. The fusion protein exhibited antibody-dependent cell mediated cytotoxicity in vitro against human tumor cells. Moreover, this fusion protein is capable of conjugating target and effector cells and displays favorable pharmacokinetics in the blood. Finally, the 264scTCR/IgG1 fusion protein is capable of reducing lung metastases in a dose dependent manner in an experimental model of metastasis. Thus, the 264scTCR/IgG1 fusion protein has potential to be used as an immunomodulatory cancer therapy that can target tumor antigens not normally recognized by antibody-based therapies.
Abstract P155: Cardiovascular Health at Young and Middle Ages and Medical Care Costs at Old Age
Authors: Cuiping Schiman, Lei Liu, Tina Shih, Lihui Zhao, Martha Daviglus, Kiang Liu, James Fries, Daniel Garside, Thanh Huyen Vu, Jeremiah Stamler, Donald Lloyd-Jones, Norrina B. Allen
Journal: Circulation (2017)

Introduction: We investigate the association between cardiovascular health at young and middle age and medical care costs and utilization in old age. Methods: We linked Chicago Heart Association (CHA) study participants’ baseline cardiovascular health (CVH) (18-59 yrs) to their Medicare claims (1991-2010) for all Part A and Part B services, including inpatient and skilled nursing facility, outpatient, home health, durable medical equipment, and hospice care. Baseline CVH is a composite measure of BP, cholesterol, diabetes, BMI, and smoking and is divided into four strata representing increasing burden. Medical care utilization (e.g., admissions and visits) and costs (in 2010 dollars) were calculated from the claims. We analyzed both the overall costs and the composition of costs among various medical care services and by CVD (non-CVD) morbidity and sex. Conditional quantile regressions were used to estimate the association between increased CVH and costs and negative binomial regressions were used for the number of inpatient admissions and outpatient visits, and the length of inpatient or hospice stay. Results: Among the 22,236 participants (222,816 person-years) 41.7% are female, 5.7% had favorable levels of all factors, 19.6% had 1+ risk factors at elevated levels, 40.9% had 1 high risk factor, and 33.7% had 2+ high risk factors. The median (mean) health care costs over the sample is $12,477 ($189,598) per person year in 2010 dollars, poorer CVH was associated with higher total medical care costs and a greater proportion of spending on home health visits (Figure). A greater CVH burden was associated with greater utilization and length of stay. Individuals with 2+ high risk factors on average have 0.22 more inpatient admissions per year and their inpatient stay is almost 2.91 days longer per year than individuals with favorable CVH. Conclusion: Unfavorable CVH early in life is associated with higher medical care cost burden in old age. Future interventions to improve CVH may result in reduced healthcare costs and utilization.
Abstract 18915: Bleeding and Vascular Complications Following PCI in Women No Longer Exceed Those of Men: A Single Center Comparison of Then (2008) versus Now (2015)
Authors: Hannah I Chaudry, Shawn X Li, Theodore B Curran, Nicholas I Buss, Bruce W Andrus, Sheila M Conley, James T DeVries
Journal: Circulation (2016)

Introduction: Historically, women have had higher vascular complications compared to men when undergoing a percutaneous coronary intervention (PCI). While increasing transradial access reduces blee...
Abstract 15462: Spontaneous Cardioversion in Nonvalvular Atrial Fibrillation in Patients Planned for Electrical Cardioversion: A Subanalysis of the ENSURE-AF Trial
Authors: Ariel A Cohen, Hein Heidbuchel, Jean-Yves Le Heuzey, Raffaele De Caterina, Jose L Merino, James Jin, Michael Melino, Shannon M Winters, Andreas Goette, Gregory Y Lip
Journal: Circulation (2017)

Background: In the ENSURE-AF study (NCT 02072434), comparable low rates of major and clinically relevant nonmajor (CRNM) bleeding and thromboembolism were observed between patients undergoing elect...
SAT0076 Synovial mast cells and responses to synthetic and biologic dmards in early and established rheumatoid arthritis
Authors: F. Rivellese, A. Nerviani, D. Mauro, S. Pagani, F. Humby, C. Pitzalis
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Mast cells (MCs) are immune cells implicated in the pathogenesis of Rheumatoid Arthritis (RA), but their presence in synovia has not been assessed systematically and their association with disease progression and treatment response is unknown. <h3>Objectives</h3> To analyse MCs in the synovia of patients with early vs established RA in correlation with histological and clinical phenotype. <h3>Methods</h3> DMARDs-naïve patients with early (&lt;12 months) RA (n=97) and patients with established RA failing synthetic DMARDs and candidate to biologic treatment (n=27) underwent ultrasound-guided synovial biopsy. Sections of paraffin embedded synovial tissue were stained with H and E to measure the degree of synovitis (Krenn Score). Sequentially cut sections were stained by immunohistochemistry to evaluate the presence of immune cells, including CD117 (c-kit) positive mast cells. Upon SQ scoring (0–4), patients were stratified into synovial pathotypes (Lymphoid, Fibroid, and Myeloid), as previously described <h3>Results</h3> In the cohort of DMARDs-naïve early RA (mean disease duration 6 months), MC+ve patients (67.7%) had significantly higher synovial inflammation (Krenn score), higher prevalence of the lymphoid pathotype, higher inflammatory markers and disease activity; however, they did not differ in terms of response to sDMARDs at 6 months (table 1, left). In established RA (mean disease duration 5 years), MC+ve patients (48.1%) had significantly higher synovial inflammatory scores and higher prevalence of the lymphoid pathotype, while systemic inflammatory markers or disease activity scores were not different. At 6 months follow-up, MC+ve patients had significantly higher rates of response to anti-TNFα (table 2, right). <h3>Conclusions</h3> We here show that early RA patients with MC+ve synovitis and high levels of local and systemic inflammation do not respond differently to synthetic DMARDs. In the context of established RA after sDMARDs failure, patients with MC+ve synovitis, despite having similar levels of systemic inflammatory markers and disease activity, had higher chances of responding to anti-TNF-α. Although the latter observation will need validation on larger cohorts, our data suggests that the analysis of synovial MCs might help defining synovial histopathology and possibly contribute to the prediction of treatment response. <h3>Reference</h3> [1] Mast cells in rheumatoid arthritis: friends or foes? Rivellese F, Nerviani A, Rossi FW, Marone G, Matucci-Cerinic M, de Paulis A, Pitzalis C. Autoimmun Rev2017Jun;16(6):557–563. doi:10.1016/j.autrev.2017.04.001 <h3>Disclosure of Interest</h3> None declared
Abstract 16472: Cardiac Biomarkers Are Associated With Death and Listing for Heart Transplantation in Pediatric Patients With Newly Diagnosed Dilated Cardiomyopathy: A Multi-Center Study From the Pediatric Cardiomyopathy Registry
Authors: Steven E Lipshultz, Joseph W Rossano, Ling Shi, John L Jefferies, Steven D Colan, Elfriede Pahl, Melanie D Everitt, Steven A Webber, Charles E Canter, Jeffrey A Towbin, Paul F Kantor, Brian Feingold, Linda J Addonizio, Jacqueline M Lamour, Stephanie M Ware, Teresa M Lee, Jason D Czachor, Hiedy Razoky, James D Wilkinson
Journal: Circulation (2017)

Background: Children with dilated cardiomyopathy (DCM) are at high risk for morbidity and death. There are no validated serum biomarkers associated with clinical events. Objective: To evaluate cardiac biomarkers as predictors of clinical endpoints (heart failure, death, or transplant listing, heart transplant). Design / Methods: Patients (<21 years of age at DCM diagnosis) were enrolled at 15 North American pediatric cardiomyopathy centers within one year of diagnosis with collection of serum, echocardiograms and clinical data at enrollment and at intervals for up to 2 years. The main hypothesis was that heart failure, myocyte injury, and inflammatory biomarkers are associated with the primary study endpoint (heart failure, death, or transplant listing, or heart transplant) <90 days of enrollment. Results: Data from 74 subjects were analyzed, median age 2.1 years at enrollment [interquartile range (IQR 0.7-12.8)], 44 (55%) female, and 61 (76%) enrolled within 90 days of diagnosis. The primary endpoint was...
Identification of trimethylamine N-oxide (TMAO)-producer phenotype is interesting, but is it helpful?
Authors: Arduino Arduini, Victor A Zammit, Mario Bonomini
Journal: Gut (2019)

We read with great interest the paper by Wu et al 1 reporting on the development of a carnitine challenge test to facilitate the identification of trimethylamine N-oxide (TMAO)-producer phenotype and host-diet-gut dysbiosis. Such a test assumes that, according to a partial reading of the literature, TMAO plays a key role in cardiovascular disease (CVD). Accordingly, the authors assert the implied importance of the potential for adverse CVD-inducing actions of compounds generating TMAO subsequent to the action of gut microbiota on dietary carnitine. However, a more objective reading of the literature shows that the biomedical community is still debating the potential involvement of TMAO in inducing …
GP workloads are made worse by shortages of common drugs
Authors: Harriet Pike
Journal: BMJ (2019)

Drug shortages are increasingly affecting GPs and patients, who may be sent back to their doctor when a medicine is out of stock at the pharmacy, the Royal Pharmaceutical Society has warned.

“Patients are being disadvantaged, as they can’t get the medicines they need when they need them,” said Ash Soni, president of the society and a community pharmacist in London. “It’s making patients run around and making GPs’ workload worse. Pharmacists are spending significant amounts of time chasing medicines, and we’re having to explain to GPs when we can’t source the medicines they have prescribed.”

Data from the Pharmaceutical Services Negotiating Committee, which represents community pharmacy contractors in England, show that the number of drugs in short supply has risen sharply in recent months. It now stands at 80, up from 45 in October 2018 and is approaching November 2017 levels, when the …
Clinical Responses of Glasdegibplus Low-Dose Ara-C, Azacitidine, and Decitabine Among Acute Myeloid Leukemia (AML) Patients Ineligible to Receive Intensive Chemotherapy: Comparative Effectiveness Using Indirect Treatment Comparison (ITC) Methods
Authors: Tracy Westley, Anna Forsythe, Timothy J Bell, Joseph C Cappelleri, Gabriel Tremblay, Geoffrey Chan
Journal: Blood (2018)