tbuckley/cabot-search huggingface dataset:
Urinary Phthalate Biomarker Concentrations and Postmenopausal Breast Cancer Risk
Authors: Katherine W Reeves, Mary Díaz Santana, JoAnn E Manson, Susan E Hankinson, R Thomas Zoeller, Carol Bigelow, Susan R Sturgeon, Donna Spiegelman, Lesley Tinker, Juhua Luo, Bertha Chen, Jaymie Meliker, Matthew R Bonner, Michele L Cote, Ting-Yuan David Cheng, Antonia M Calafat
Journal: JNCI Journal of the National Cancer Institute (2019)

Abstract Background Growing laboratory and animal model evidence supports the potentially carcinogenic effects of some phthalates, chemicals used as plasticizers in a wide variety of consumer products, including cosmetics, medications, and vinyl flooring. However, prospective data on whether phthalates are associated with human breast cancer risk are lacking. Methods We conducted a nested case-control study within the Women’s Health Initiative (WHI) prospective cohort (n = 419 invasive case subjects and 838 control subjects). Control subjects were matched 2:1 to case subjects on age, enrollment date, follow-up time, and WHI study group. We quantified 13 phthalate metabolites and creatinine in two or three urine samples per participant over one to three years. Multivariable conditional logistic regression analysis was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for breast cancer risk associated with each phthalate biomarker up to 19 years of follow-up. Results Overall, we did not observe statistically significant positive associations between phthalate biomarkers and breast cancer risk in multivariable analyses (eg, 4th vs 1st quartile of diethylhexyl phthalate, OR = 1.03, 95% CI = 0.91 to 1.17). Results were generally similar in analyses restricted to disease subtypes, to nonusers of postmenopausal hormone therapy, stratified by body mass index, or to case subjects diagnosed within three, five, or ten years. Conclusions In the first prospective analysis of phthalates and postmenopausal breast cancer, phthalate biomarker concentrations did not result in an increased risk of developing invasive breast cancer.
THU0683 Predictors for preterm delivery among pregnant women with rheumatoid arthritis and juvenile idiopathic arthritis
Authors: C.J.F. Smith, F. Förger, C. Chambers
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> It has previously been shown that pregnant women with inflammatory arthritis are at an increased risk for preterm delivery (PTD), yet it remains unclear what underlying maternal factors may drive this excess risk. <h3>Objectives</h3> The aim of our study is to identify overall predictors for PTD among women with rheumatoid arthritis (RA) and juvenile idiopathic arthritis (JIA) and to analyse the contribution of maternal disease activity, medication use, and comorbid pregnancy conditions on the risk for PTD in this population. <h3>Methods</h3> Data were obtained from the Organisation of Teratology Information Specialists (OTIS) Autoimmune Disease in Pregnancy Project, a prospective cohort study among pregnant women in the U.S. and Canada. Women who enrolled between 2004 and 2017 prior to 19 weeks' gestation, had not enrolled with a previous pregnancy, and delivered at least one live born infant were considered eligible for analysis. All data were obtained by maternal report via telephone interviews and confirmed in the medical record when available. For our statistical analysis, Poisson regression with robust standard errors was used to estimate multivariable adjusted risk ratios. <h3>Results</h3> Mothers with RA and JIA had a higher risk of PTD, preterm labour, early term delivery, and caesarian section versus comparison women. Women with RA additionally had a higher risk of gestational diabetes mellitus (GDM), and women with JIA had a higher risk of preeclampsia versus the comparison group. Active disease (defined as patient activity scale (PAS) score &gt;3.70) was associated with PTD among women with RA both at intake and anytime during pregnancy, and this association remained after adjustment for corticosteroid (CS) use (aRR 1.60, 95% CI 1.12–2.30; aRR 1.54, 95% CI 1.08–2.20, respectively). CS use in all three trimesters was associated with PTD among women with both RA and JIA, an association that remained after multivariable adjustment for maternal factors including disease activity. Use of non-steroidal anti-inflammatory drugs (NSAIDs) in the first trimester was associated with PTD in women with JIA (aRR 2.31, 95% CI 1.04–5.14). Additional analysis showed that preeclampsia was associated with a higher risk of PTD among both RA and JIA women (aRR 1.92, 95% CI 1.12–3.31; aRR 3.01, 95% CI 1.10–8.23, respectively) but not in the comparison group. GDM and caesarian section were associated with a higher risk of PTD exclusively among RA women (aRR 1.84, 95% CI 1.07–3.15 and aRR 1.58, 95% CI 1.09–2.28, respectively) and fever during pregnancy increased the risk for PTD exclusively among women with JIA (aRR 3.45, 95% CI 1.47–8.08). <h3>Conclusions</h3> Women with RA and JIA are at risk for preterm delivery. Maternal disease activity and medication use, particularly corticosteroid use, may explain much of this excess risk. <h3>Disclosure of Interest</h3> None declared
Assessment of Spending in Medicare Part D If Medication Prices From the Department of Veterans Affairs Were Used
Authors: Brett Venker, Kevin B. Stephenson, Walid F. Gellad
Journal: JAMA Internal Medicine (2019)

This study uses the most recent national data available from Medicare and the Department of Veterans Affairs to quantify the savings Medicare Part D would achieve if it paid the same prices for prescription drugs currently paid by the Department of Veterans Affairs.
Clinical-grade stem cell–derived retinal pigment epithelium patch rescues retinal degeneration in rodents and pigs
Authors: Ruchi Sharma, Vladimir Khristov, Aaron Rising, Balendu Shekhar Jha, Roba Dejene, Nathan Hotaling, Yichao Li, Jonathan Stoddard, Casey Stankewicz, Qin Wan, Connie Zhang, Mercedes Maria Campos, Kiyoharu J. Miyagishima, David McGaughey, Rafael Villasmil, Mary Mattapallil, Boris Stanzel, Haohua Qian, Wai Wong, Lucas Chase, Steve Charles, Trevor McGill, Sheldon Miller, Arvydas Maminishkis, Juan Amaral, Kapil Bharti
Journal: Science Translational Medicine (2019)

Considerable progress has been made in testing stem cell-derived retinal pigment epithelium (RPE) as a potential therapy for age-related macular degeneration (AMD). However, the recent reports of oncogenic mutations in induced pluripotent stem cells (iPSCs) underlie the need for robust manufacturing and functional validation of clinical-grade iPSC-derived RPE before transplantation. Here, we developed oncogenic mutation-free clinical-grade iPSCs from three AMD patients and differentiated them into clinical-grade iPSC-RPE patches on biodegradable scaffolds. Functional validation of clinical-grade iPSC-RPE patches revealed specific features that distinguished transplantable from nontransplantable patches. Compared to RPE cells in suspension, our biodegradable scaffold approach improved integration and functionality of RPE patches in rats and in a porcine laser-induced RPE injury model that mimics AMD-like eye conditions. Our results suggest that the in vitro and in vivo preclinical functional validation of iPSC-RPE patches developed here might ultimately be useful for evaluation and optimization of autologous iPSC-based therapies.
AB0091 Mechanical exposure and diacerein treatment modulates integrin-fak-mapks mechanotransduction in human osteoarthritis chondrocytes
Authors: B. Lohberger, L. Weigl, A. Mann, W. Kullich, A. Leithner, B. Steinecker-Frohnwieser
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Progression of osteoarthritis (OA) is characterised by destruction of articular cartilage, thickening of subchondral bone, and formation of osteophytes. The disease modifying OA drug (DMOAD) diacerein functions as a slow acting drug through anti-inflammatory, anti-catabolic, and pro-anabolic effects on cartilage and the synovial membrane. Mechanical loading of joint tissue directly affects the homeostasis of matrix degrading enzyme production and matrix repair. <h3>Objectives</h3> To explore the impact of diacerein and moderate mechanical stimulation on the anabolic metabolism of OA and non-OA chondrocytes, as well as on the integrin-FAK-MAPKs signal transduction cascade in these cells. <h3>Methods</h3> Mechanical stimulation was applied in terms of three different intensities by the Flexcell tension system. Influence on catabolic parameters such as MMPs, ADAMTS, and IL-6 were assessed by qPCR. Changes in phosphorylation of FAK, STAT3 as well as MAP kinases were verified by western blot analysis. Intracellular calcium was measured fluorimetrically using fura-2. <h3>Results</h3> Mechanical stimulation at moderate intensity (SM/SA) proved to be most efficient in terms of reducing production of matrix degrading enzyme and IL-6 expression. Treatment with diacerein by itself and diacerein in combination with SM/SA reduced phosphorylation of FAK and STAT3, which is more pronounced in OA cells. Pretreatment with diacerein for 7 days resulted in an increase in the sensitivity to Yoda1, the agonist for the mechanically activated ion channel Piezo1. However, in OA cells a significant reduction in Piezo1 expression was observed following treatment with diacerein. <h3>Conclusions</h3> Cyclic tensil strain can reduce matrix destroying enzymes, and when used in combination with diacerein, the activity of integrin signalling components is changed. The observed effects can be mainly attributed to diacerein's capacity to modulate STAT3 and Piezo1, which are both potential targets to prevent the progression of OA. <h3>Disclosure of Interest</h3> None declared
Reducing Venous Thrombosis with Antithrombin Supplementation in Patients Undergoing Treatment for ALL with Asparaginase Based Regimens
Authors: Alexandra Rezazadeh, Gemlyn George, Nicole Pearl, Cole McCoy, Felicia Zook, Benjamin Jung, Aschenbrenner Emilie, Mindy Waggoner, Sameem Abedin, Lyndsey Runaas, Laura C. Michaelis, Karen-Sue B. Carlson, Lisa Baumann Kreuziger, Ehab L. Atallah
Journal: Blood (2018)
Post Treatment Complete Metabolic Remission By 18f-FDG PET/CT As a Strong Prognostic Predictor of Survival in Large B-Cell Lymphomas
Authors: Dina Sameh Soliman, Prem Chandra, Lajos Szabados, Ruba Yasin, Mohamed A Yassin, Einas Alkuwari, Ahmed Al-Sabbagh, Firyal Ibrahim, Amna Gamil, Abdulqadir Jeprel Nashwan
Journal: Blood (2018)
AB0957 Severity of skin symptoms is not associated with musculoskeletal manifestations in patients with psoriasis
Authors: Y. Yamada, K. Inui, T. Okano, Y. Sugioka, H. Yoshimura, K. Mamoto, T. Koike, M. Tada, C. Tateishi, E. Yonezawa, A. Natsumi, Y. Fukunaga, D. Tsuruta, H. Nakamura
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Among patients with psoriasis, risk factors for developing musculoskeletal manifestations, known as psoriatic arthritis (PsA), are not recognised well. <h3>Objectives</h3> The aim of this study is to clarify the relationship between severity of skin disease and arthritis. <h3>Methods</h3> Psoriasis patients referred from dermatologists for assessment of musculoskeletal manifestations between <sup>June 2015</sup> and July 2017 were enrolled. Their age, comorbidity, disease duration and treatment were collected. Presence of inflammatory back pain, sacroiliac joint tenderness or enthesitis were examined. Severity of skin symptoms were evaluated by dermatologists in Psoriasis area and severity index (PASI). Psoriatic arthritis screening and evaluation (PASE) and disease activity score (DAS28 ESR) were also evaluated. PsA was diagnosed by The Classification for Psoriatic Arthritis (CASPAR) criteria assisted with musculoskeletal ultrasound examination. <h3>Results</h3> Among 107 patients with psoriasis referred from dermatologists during designated period, 63 patients were diagnosed as PsA. These PsA patients were compared with 44 patients who had no arthritis (PsO). Multiple logistic regression analysis showed neither of age, sex, PASI, disease duration, rheumatoid factor (RF), CRP or Matrix Metalloproteinase-3 (MMP3) had no association with presence of PsA (table 1). Among 63 patients with PsA, those using NSAIDs (p=0.028), those with inflammatory back pain (p=0.002) and male patients (p=0.017) had significantly high PASI. PASI significantly correlated with age (Spearman's correlation coefficient R=−0.303: p=0.016), body height (R=0.301: p=0.019) and weight (R=0.383: p=0.002), but not with DAS28 ESR, MMP3 or disease duration (table 2). Table 1 multiple logistic regression analysis for presence of PsA <h3>Conclusions</h3> PASI did not associate with presence of arthritis. Furthermore, even DAS28 ESR, reflecting musculoskeletal manifestations, or disease duration did not correlated with PASI among patients with PsA. These indicates severity of skin symptoms is not associated with musculoskeletal manifestations in patients with psoriasis. <h3>Disclosure of Interest</h3> None declared
Abstract 20897: Patient-Reported Outcomes in Tetralogy of Fallot: Baseline Results From a Prospective, International, Multi-Site Study
Authors: Rachel M Wald, Michael Farkouh, Christopher Caldarone, Nagib Dahdah, Frédéric Dallaire, Christian Drolet, Jasmine Grewal, Edward Hickey, Camilla Kayedpour, Paul Khairy, Benedetta Leonardi, Brian McCrindle, Syed Najaf Nadeem, Ming Yen Ng, Erwin Oechslin, Andrew Redington, Candice Silversides, Edythe Tham, Judith Therrien, Isabelle Vonder Muhll, Andrew Warren, Bernd Wintersperger, Adrienne Kovacs
Journal: Circulation (2017)

Introduction: In addition to understanding causes of morbidity and mortality following tetralogy of Fallot repair (rTOF), the importance of patient-reported outcomes (PROs) such as quality of life (QOL) is increasingly being recognized. Hypothesis: We hypothesized that PROs in rTOF would be associated with selected sociodemographic factors, functional status, and/or clinical variables. Methods: As part of a prospective study of patients ≥12 years with rTOF and significant pulmonary regurgitation, participants completed PRO surveys: SF-12 Health Status (physical component summary [PCS] and mental component summary [MCS] t-scores), EQ-5D (5 dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression), and a 0-100 QOL linear analogue scale (QOL-LAS). With multivariable regression analysis, we determined the association between PROs and selected predictors. Results: We studied n=627 participants (55% male, 26±13 years, 75% adult) at 14 sites (North America, Europe and Asia). Median age at repair was 1.6 years (IQR 0.6, 4.2). In general, scores on the SF-12 and QOL-LAS suggested good outcomes: SF-12 PCS &lt;18 years 52±6 and ≥18 years 51±9; SF-12 MCS &lt;18 years 52±9 and ≥18 years 49±10; QOL-LAS &lt;18 years 83±14 and ≥18 years 78±16. On the EQ-5D, difficulties were reported with usual activities (16%), pain (25%) and anxiety/depression (38%). In multivariable regression analysis, younger age at enrollment emerged as an independent predictor of better physical health status and worse mental health status (p=0.0005 and p=0.029, respectively), but not QOL. Better NYHA functional class was a predictor of better SF-12 PCS and MCS (p&lt;0.0005 and p=0.002) as well as better QOL (p&lt;0.0001). Other factors (including complexity of underlying TOF anatomy, previous shunt palliation and need for arrhythmia intervention) were not associated with PROs. Conclusions: Age and NYHA functional class at enrollment were found to be predictors of PROs in rTOF. While global measures of health status and QOL (SF-12 and QOL-LAS) suggest relatively good PROs, this study demonstrates the importance of inquiring about specific health problems (EQ-5D) to achieve a richer understanding of PROs in order to potentially maximize patient well-being.
Jan Gösta Waldenström and rheumatology
Authors: Frank A Wollheim
Journal: Annals of the Rheumatic Diseases (2019)

On 2 September 1943, Jan Waldenstrom (1906–1996) successfully submitted a paper to Acta Medica Scandinavica describing two patients with a new disease. The discovery was to make him world famous.1 This year marks the 75th anniversary of macroglobulinaemia and it coincided with the 10th biennial international workshop of Waldensm’s macroglobulinaemia, discussing advances in the genetic basis, pathogenesis and treatments of the disease.2 Jan Waldenstrom (JW) would have enjoyed this workshop immensely, sharing the information that over 95% of the patients had somatic mutations affecting the MYD88 gene on the second chromosome as well as the impressive advances in treatment. Attending this excellent meeting brought back memories of my time as Waldenstrom’s PhD student and triggers me to compose this vignette, focusing on connexions between the interests of my mentor and rheumatology. For a more comprehensive account of Jan Waldenstrom’s legacy, I recommend Robert Kyle’s superb obituary, published in Blood , a journal JW was attached to from its start.3 

After the successful defence of his landmark PhD thesis on acute intermittent porphyria,4 Waldenstrom’s interest focused on haematology. He worked in Uppsala, a university where the study of proteins had prominence. There, The Svedberg had developed the ultracentrifuge and Arne Tiselius the free electrophoresis and Robin Fahreus the elevated sedimentation rate (ESR). Conditions with ESR caught JW’s special attention. An early witness is a paper from 1937, analysing five cases diagnosed with uveoparotitis, a rare condition most prevalent in women and then considered by many to be a form of tuberculosis. He noticed several multiorgan manifestations, the similarities with von Mikulicz disease and Boeck’s sarcoid, the presence of high ESR, unspecific Wassermann reaction, absence of proof of tuberculosis, presence of …
Report from the National Institute of Allergy and Infectious Diseases workshop on “Atopic dermatitis and the atopic march: Mechanisms and interventions”
Authors: Wendy F. Davidson, Donald Y.M. Leung, Lisa A. Beck, Cecilia M. Berin, Mark Boguniewicz, William W. Busse, Talal A. Chatila, Raif S. Geha, James E. Gern, Emma Guttman-Yassky, Alan D. Irvine, Brian S. Kim, Heidi H. Kong, Gideon Lack, Kari C. Nadeau, Julie Schwaninger, Angela Simpson, Eric L. Simpson, Jonathan M. Spergel, Alkis Togias, Ulrich Wahn, Robert A. Wood, Judith A. Woodfolk, Steven F. Ziegler, Marshall Plaut
Journal: Journal of Allergy and Clinical Immunology (2019)
In uncomplicated acute appendicitis, 61% of patients initially treated with antibiotics had not had appendectomy at 5 years
Authors: Markos Kalligeros, Eleftherios Mylonakis
Journal: Annals of Internal Medicine (2019)

Source Citation Salminen P, Tuominen R, Paajanen H, et al. Five-year follow-up of antibiotic therapy for uncomplicated acute appendicitis in the APPAC randomized clinical trial. JAMA. 2018;320:1259-65. 30264120
Pay, workflow, and staff vacancies are most pressing issues, say hospital doctors
Authors: Abi Rimmer
Journal: BMJ (2019)

Most hospital doctors say that ending the decline in their pay and benefits is more important than any other issue, a survey has found.

The Hospital Consultants and Specialists Association (HCSA) surveyed its members late last year and received responses from 975—about a quarter of members.

Of 940 hospital doctors who responded to the question “Which of the following do you think are the three most important issues to you and your colleagues?” some 75% (702) selected an end to declining pay and benefits …
AB1307 Disease burden of autoimmune inflammatory rheumatic diseases in south korea
Authors: H. Kim, S.-M. Choi, S.-K. Cho, S.-Y. Jung, D. Kim, E.J. Jang, Y.-K. Sung
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Little is known about the epidemiology and disease burden of autoimmune inflammatory rheumatic diseases (AIRDs) in South Korea. <h3>Objectives</h3> To investigate the prevalence and direct medical cost of AIRDs in South Korea. <h3>Methods</h3> The prevalence of AIRDs including seropositive rheumatoid arthritis (RA), ankylosing spondylitis (AS), systemic lupus erythematosus (SLE), vasculitides, and other connective tissue diseases was calculated, and their trends between 2012 and 2016 were observed using nationwide claims database and the Rare Intractable Disease registration program. Direct medical costs of each AIRD in 2016 were estimated on the basis of claims charged for specific ICD-10 diagnostic codes. <h3>Results</h3> Among the all AIRDs, seropositive RA was most prevalent in Korea with prevalence of 188.5/100,000 persons in 2016, followed by AS (58.7/100,000), SLE (38.0/100,000), Behçet disease (29.2/100,000), Sjögren syndrome (23.5/100,000), and systemic sclerosis (7.1/100,000). Relatively low prevalence was observed in inflammatory myositis (4.5/100,000), polymyalgia rheumatica (4.1/100,000), psoriatic arthritis (PsA, 2.5/100,000), and each vasculitis (0.6~3.1/100,000). Prevalence of most AIRDs had been increased from 2012 to 2016, while their sex and age distribution were not changed significantly. Total direct medical costs in 2016 of overall AIRDs were $263,136,087, which were mostly composed of direct medical expenditures for seropositive RA, AS, and SLE. For the direct medical cost per person, microscopic polyangiitis ($6,223.3) was the highest, followed by PsA ($3,603.7), Wegener granulomatosis ($3,002.6), dermatomyositis ($2,643.1), and AS ($2,603.9). <h3>Conclusions</h3> Most prevalent AIRD in Korea was seropositive RA, followed by AS, Sjogren's syndrome, SLE, Behcet's disease, and systemic sclerosis. Direct medical cost per person was high in microscopic polyangiitis, PsA, Wegener granulomatosis, dermatomyositis, and AS. <h3>Disclosure of Interest</h3> None declared
Analysis of the factors associated with diagnostic skin test positivity in immediate‐type hypersensitivity reactions due to proton pump inhibitors
Authors: Seçil Kepil Özdemir, Aslı Gelincik, Nail Paksoy, Gözde Köycü Buhari, Ferda Öner Erkekol, Adile Berna Dursun, Ebru Çelebioğlu, Gül Karakaya, Sevim Bavbek
Journal: Allergy (2019)

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Single-Molecule hsTnI and Short-Term Risk in Stable Patients With Chest Pain
Authors: James L. Januzzi, Sunil Suchindran, Udo Hoffmann, Manesh R. Patel, Maros Ferencik, Adrian Coles, Jean-Claude Tardif, Geoffrey S. Ginsburg, Pamela S. Douglas
Journal: Journal of the American College of Cardiology (2019)