tbuckley/cabot-search huggingface dataset:
Abstract P002: The American Heart Association’s Life’s Simple 7 and Risk of Incident Atrial Fibrillation: the REasons for Geographic and Racial Differences in Stroke Study
Authors: Parveen Garg, Wesley O’Neal, Adedotun Ogunsua, George Howard, Elsayed Soliman, Mary Cushman
Journal: Circulation (2017)

Background: The American Heart Association has identified metrics of ideal cardiovascular (CV) health known as Life’s Simple 7 (LS7), including blood pressure, body mass index, cholesterol, cigarette smoking, diet, glucose, and physical activity, to target primary cardiovascular disease prevention. While poor control of these metrics are individually associated with a higher risk of atrial fibrillation (AF), the association of the combination of these metrics with incident AF has not been evaluated. We determined the relationship between LS7 and incident AF in a cohort of middle and older-aged adults. Methods: The REasons for Geographic And Racial Differences in Stroke Study is a biracial prospective study of 30,249 individuals. Eligible participants included those without AF who had data on all LS7 components at baseline and completed a follow-up exam 10 years later. An overall LS7 score was calculated as the sum of the LS7 component scores (0 to 2 points per component). This score was classified as inadequate (0-4), average (5-9), or optimum (10-14) CV health. Incident AF was identified at follow-up by either electrocardiogram or a self-reported medical history of a physician diagnosis. Results: 9,576 participants (mean age=63; 57% women; 30% black) were included. In adjusted logistic regression analyses, optimum CV health (referent=poor) and each one point higher LS7 score were associated with a lower incident AF (Table). Associations did not differ by race or gender (interaction p-values of 0.51 and 0.49 respectively). Conclusions: Better CV health, as defined by the LS7 score, is associated with a reduction in the incidence of AF. Further study into whether efforts to improve the population’s CV health lower AF incidence is needed.
Efficacy of patupilone in advanced local or metastatic gastric cancer: A phase IIa trial
Authors: K. W. Hsin, M. Boyer, M. Ducreux, M. Liu, R. Soo, W. Yeo, K. J. Williams, A. Johri
Journal: Journal of Clinical Oncology (2006)

4069 Background: Although the use of taxanes has produced encouraging response rates in patients with advanced local or metastatic gastric cancer, outcomes remain unsatisfactory. Patupilone (EPO906; epothilone B), a novel microtubule stabilizer, has demonstrated anti-tumor activity against a broad range of tumors in vitro and in animal models. The present trial evaluated the efficacy of patupilone in patients with locally advanced or metastatic gastric cancer. Methods: Patients with confirmed gastric adenocarcinoma (defined by RECIST) received patupilone 2.5 mg/m 2 /wk by single 5- to 7-minute IV infusion for 3 weeks, followed by 1 week off (4-week cycle). Additional inclusion criteria: WHO performance status ≤2, age ≥18 years, life expectancy ≥3 months, and no major hematologic, renal, or hepatic impairment. The primary objective of this open-label, single-arm, 2-stage, multicenter study was to determine the objective response rate (using RECIST) of treatment with patupilone in this population. Results: All 22 patients enrolled were evaluable. Mean age was 61.1 years, 63.6% were men, and 72.7% were oriental. Of 18 patients (81.8%) who completed the study, 10 (45.5%) had disease progression and 8 (36.4%) died from the disease; of 4 discontinuations, 3 were due to adverse events (AEs) and 1 to abnormal alkaline phosphatase. Overall response: 2 patients had partial responses, 6 disease stabilization, 12 disease progression, and 2 unknown. The duration of response in the 2 partial responders was 176 and 113+ days, with the latter censored at 113 days. The most frequently reported AEs were diarrhea (n = 18), nausea (n = 14), vomiting (n = 13), abdominal pain (n = 10), and fatigue (n = 10). Of these AEs, 9 were grade 3 (4 diarrhea, 3 vomiting, 1 nausea, and 1 fatigue) and 2 were grade 4 (1 nausea and 1 vomiting). Grade 4 AEs also included 1 gastric outlet obstruction and 1 dehydration. Conclusions: Patupilone resulted in an overall tumor response/disease stabilization rate of 36.4%, was well tolerated, and may prove to be a viable alternative to taxane treatment in advanced local/metastatic gastric cancer. [Table: see text]
Hepatocyte-specific suppression of microRNA-221-3p mitigates liver fibrosis
Authors: Hsin-Chieh Tsay, Qinggong Yuan, Asha Balakrishnan, Marina Kaiser, Selina Möbus, Emilia Kozdrowska, Marwa Farid, Pia-Katharina Tegtmeyer, Katharina Borst, Florian W.R. Vondran, Ulrich Kalinke, Andreas Kispert, Michael P. Manns, Michael Ott, Amar Deep Sharma
Journal: Journal of Hepatology (2018)
Subsequent Treatment Outcomes of Multiple Myeloma Refractory to CD38-Monoclonal Antibody Therapy
Authors: Robert Frank Cornell, Ujjawal H Gandhi, Arjun Lakshman, Zhubin Gahvari, Megan Helena Jagosky, Elizabeth McGehee, William Varnado, Ridhi Gupta, Saurabh Chhabra, Mark A. Fiala, Ehsan Malek, Joshua Mansour, Barry Paul, Alyssa Barnstead, Saranya Kodali, Amarendra K. Neppalli, Michaela Liedtke, Kelly N. Godby, Yubin Kang, Ankit Kansagra, Elvira Umyarova, Emma C. Scott, Parameswaran Hari, Ravi Vij, Saad Z. Usmani, Natalie Scott Callander, Luciano J Costa, Shaji K. Kumar
Journal: Blood (2018)
Survival outcomes in patients (pts) with KRAS/NRAS (RAS) wild-type (WT) metastatic colorectal cancer (mCRC) and non-liver-limited disease (non-LLD): Data from the PRIME study.
Authors: Jean-Yves Douillard, Josep Tabernero, Salvatore Siena, Marc Peeters, Reija Koukakis, Jan-Henrik Terwey, Roger Sidhu
Journal: Journal of Clinical Oncology (2014)

3550^ Background: ESMO guidelines recommend upfront treatment with an active combination regimen for mCRC pts with multiple metastases and those with more limited disease (Schmoll et al, 2012). Panitumumab (pmab) + FOLFOX4 is an active regimen that improved overall survival (OS) vs FOLFOX4 alone in the 1st-line treatment of RAS WT mCRC (PRIME study). In this exploratory analysis of PRIME, we report the efficacy of pmab + FOLFOX4 vs FOLFOX4 in pts with non-LLD. Methods: PRIME was a randomized (1:1) phase 3 study comparing the efficacy and safety of pmab 6.0 mg/kg Q2W + FOLFOX4 vs FOLFOX4 in pts with no prior chemotherapy for mCRC. In this exploratory analysis conducted when ≥80% of pts had an OS event, median progression-free (PFS) and OS were estimated for pts with RAS WT (KRAS/NRAS exons 2-4 assessed, including codon 59) non-LLD. 3-year OS rates were also evaluated. Data were summarised descriptively and tested for significance using Cox’s proportional hazards models. Results: Of the 505 pts with RAS WT mCRC, 416 had non-LLD. Treatment arms were well balanced with respect to baseline sex, age and metastatic sites. Overall, 82% of pts had liver involvement, 51% had ≥3 metastatic sites (median 3 [range 1-6]) and median LDH was 373 (range 4-5780) U/L. Median PFS and OS were longer in RAS WT non-LLD pts receiving pmab + FOLFOX4 vs FOLFOX4 (Table). 3-year OS rates were 31% vs 23% for non-LLD pts receiving pmab + FOLFOX4 vs FOLFOX4, respectively. Numeric benefits were also observed in LLD patients receiving pmab + FOLFOX4. Conclusions: This post-hoc analysis suggests that the PFS and OS benefits observed with 1st-line pmab + FOLFOX4 vs FOLFOX4 in the overall PRIME population are also seen in the subgroup of pts who have non-LLD. Clinical trial information: NCT00364013. Non-LLD (n=416) LLD (n=89) Pmab + FOLFOX4 (n=205) FOLFOX4 (n=211) Pmab + FOLFOX4 (n=48) FOLFOX4 (n=41) PFS events, n 181 192 38 37 Median PFS, months 11.1 8.0 11.3 9.9 HR (95% CI); p valuea 0.73 (0.60-0.90); 0.0027 0.75 (0.48-1.19); 0.2223 OS events, n 166 186 32 31 Median OS, months 23.8 18.4 40.7 33.4 HR (95% CI); p valuea 0.78 (0.63-0.96); 0.0185 0.71 (0.43-1.16); 0.1737 Abbreviations: CI, confidence intervals; HR, hazard ratio. a Descriptive p value.
Erratum: The anti-IgE antibody omalizumab reduces exacerbations and steroid requirement in allergic asthmatics (European Respiratory Journal (2001) vol. 18 (254-261))
Authors: M. Solèr, J. Matz, R. Townley, R. Buhl, J. O'Brien, H. Fox, J. Thirlwell, N. Gupta, G. Della Cioppa
Journal: European Respiratory Journal (2001)
Abstract 18440: Hospital Engagement in Clinical Trial Participation Following Acute Myocardial Infarction - Insights From the National Cardiovascular Data Registry
Authors: Amit N Vora, Anita Chen, Alexander Fanaroff, Robin Mathews, Jacob Udell, Laine Thomas, Tracy Wang
Journal: Circulation (2017)

Background: While we know that few eligible MI patients participate in clinical trials in the US, little is known about the hospitals that offer clinical trial enrollment opportunities. Methods: We examined rates of clinical trial enrollment across 279,832 MI patients treated at 692 ACTION Registry - GWTG hospitals from 2008-2014. Among the 167,445 patients over age 65, we compared 30-day and 1-year mortality and MACE (death, readmission for MI, heart failure, or stroke) between trial and non-trial hospitals using linked Medicare claims data. Results: Only 330 (48%) hospitals enrolled MI patients in a clinical trial. Among enrolling hospitals, the mean proportion of MI patients enrolled was 2.1% (SD 4.6). Overall, only 1.2% of MI patients enrolled in a clinical trial. Hospitals that enrolled patients in clinical trials were more likely to be larger (median 351 vs 244 beds, p<0.001) and teaching hospitals (23.9% vs 10.2%, p<0.001). Trial hospitals had higher proportions of patients achieving every eligible...
Abstract 020: Heartbreaking Careers in Old Age: Retirement Sequences as a Non-Traditional Risk Factor for Cardiovascular Diseases
Authors: Felipe Diaz-Toro, Ignacio Madero-Cabib, Esteban Calvo, Ursula Staudinger
Journal: Circulation (2018)

Background: Traditional factors leave substantial risk for incident cardiovascular disease (CVD) unexplained. Recent literature addressing this limitation identifies non-traditional risk factors, such as depression and clinical biomarkers. This study explored retirement sequences as a new non-traditional risk factor for CVD among older Americans. Methods: Heart disease and stroke incidence were measured for 7,880 Health and Retirement Study participants age 70 and over. Non-parametric survival curves and time-discrete survival models were used to compare the succeeding incidence of CVD across the retirement sequences that individuals followed between ages 60-61 and 70-71. We employed six holistic types of retirement sequences: (i) early for individuals who completely retired at or before age 62; (ii) complete for the conventional normative model of retirement by which people who are working in full-time jobs completely retire at the legally established age; (iii) ambiguous for people out of the labor force who shifted into retirement; (iv) partial for subjects with full-time jobs that claimed partial pension benefits in their early 60s; (v) compact for individuals moving from part-time positions into partial retirement; and (vi) late for individuals with full-time employments until their late 60s. These sequences were measured as longitudinal pathways of labor-force statuses and transitions measured in two-year intervals between the ages 60-61 to 70-71 years. Models were fitted for the whole sample, as well as males and females separately, adjusting for the probability of dying before CVD onset, sociodemographics, traditional risk factors, and clinical characteristics. Results: Out of all participants, 78.1% (6154/7880) reported at least one adverse cardiovascular event after age 70. Individuals following retirement sequences characterized by a progression from full-time jobs to either early retirement (heart disease, HR 3.07 CI95% 2.89-3.26 p&lt;.001; stroke, HR:2.75 CI95% 2.53-2.96 p&lt;.001) or retirement at the state pension age (heart disease, HR:3.73 CI95% 3.52-3.93 p&lt;.001; stroke, HR:2.30 CI95% 2.07-2.54 p&lt;.001), as well as people out of the labor force who move into retirement (heart disease, HR:2.36 CI95% 2.12-2.60 p&lt;.001; stroke, HR:2.72 CI95% 2.44-3.01 p&lt;.001) experienced a higher risk for heart disease and stroke relative to individuals who kept on working past the retirement age. However, the effects are stronger for heart disease among women and stroke among men. Conclusions: Retirement sequences may indeed be regarded as a non-traditional risk factor for CVD in aging populations. Keywords: Retirement-Heart disease-Stroke-Work
SP0158 Update of eular recommendations for vaccination of patients with autoimmune inflammatory rheumatic diseases
Authors: O. Elkayam
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Objectives</h3> A European League Against Rheumatism (EULAR) Task Force was established to update the recommendations for vaccination of patients with autoimmune inflammatory rheumatic diseases (AIIRD) published in 2011. <h3>Methods</h3> Following the latest version of the EULAR Standardised Operating Procedures (SOP), three systematic literature reviews were conducted to present the new evidence published between 2009–2017 regarding the prevalence of vaccine preventable diseases among patients with AIIRD, the efficacy and safety of vaccines recommended for adults, and the effect of disease modifying drugs on the response to vaccines. After the presentation of the new evidence to the Task Force, overarching principles and recommendations were formulated. Evidence was graded in categories I–IV, the strength of recommendations was graded in categories A–D, and Delphi voting was applied to determine the level of agreement between the experts of the Task Force. <h3>Results</h3> A total of 6 overarching principles and 9 recommendations were formulated. The first two overarching principles focus on the responsibility of the treating physician for a yearly assessment of the vaccination status of AIIRD patients. An individualised vaccination program should be suggested and explicitly discussed with all patients. The next overarching principles address the timing of vaccination. Preferably patients are vaccinated during stable disease and prior to planned immunosuppression, in particular prior to B-cell depleting treatment. Non-live vaccines can be safely provided to AIIRD patients under immunomodulating treatments, whereas the administration of live attenuated vaccines should be avoided under immunomodulating treatment, with the possible exceptions of herpes zoster and MMR. Recommendations 1 to 7 refer to the administration of specific vaccines. Influenza and pneumococcal (a combination of PCV 13 and PPSV23) vaccines should be strongly considered for all patients with AIIRD. Herpes zoster, human papilloma virus, hepatitis A and B, yellow fever, and tick-borne encephalitis vaccines should be considered in AIIRD patients at risk. Newly formulated recommendations 8 and 9 address the vaccination approach to household members and newborns of patients with AIIRDs. Immunocompetent household members of patients with AIIRD should be encouraged to receive vaccines according to national guidelines with the exception of oral poliomyelitis vaccine. Live attenuated vaccines should be avoided during the first 6 months of life in newborns of mothers treated with biologics during the second half of pregnancy <h3>Conclusions</h3> The 2017 EULAR recommendations provide an up-to-date guidance on the management of vaccinations in patients with AIIRDs. The dissemination of the data to health professionals and patients and implementation of the recommendations will help to prevent vaccine preventable diseases in the AIIRD population. <h3>Disclosure of Interest</h3> None declared
Challenges in interpreting trends in testing for α<sub>1</sub>-antitrypsin deficiency in COPD patients from UK primary care
Authors: Daniel R. Morales
Journal: European Respiratory Journal (2018)

<b>Apparent increasing trends in blood test requesting observed using UK primary care electronic medical records (EMRs) may be confounded by adoption of electronic test requesting systems linked to EMRs rather than changes in clinical practice</b>http://ow.ly/M3Er30mIsJq
Bone marrow MSCs in MDS: contribution towards dysfunctional hematopoiesis and potential targets for disease response to hypomethylating therapy
Authors: Zhiyong Poon, Niraja Dighe, Subhashree S. Venkatesan, Alice M. S. Cheung, Xiubo Fan, Sudipto Bari, Monalisa Hota, Sujoy Ghosh, William Y. K. Hwang
Journal: Leukemia (2018)

The study of myelodysplastic syndromes (MDS) in murine models has now indicated the possible involvement of the bone marrow microenvironment in the generation of dysplastic hematopoietic cells. However, there is scant work on patient samples and the role of hypomethylating agents on the bone marrow stromal cells of MDS patients is unclear. We show that human MDS-MSCs exhibit phenotypic, transcriptomic and epigenetic abnormalities. Stimuli provided by MDS-MSCs impaired the growth and function of healthy HSPCs, which is further sustained autonomously in HSPCs for significant periods of time resulting in a failure for active hematopoietic engraftment across primary and secondary transplant recipients (chimerism: 0.34–91% vs 2.78%, engraftment frequencies: at 0.06 ± 0.02 vs full engraftment for MDS-MSC vs healthy groups, respectively). Hypomethylation of MDS-MSCs improved overall engraftment in most of the MDS-MSC groups tested (2/7 with p < 0.01, 3/7 with p < 0.05 and 2/7 with no significant difference). MDS-MSCs that fail to respond to hypomethylating therapy are associated with patients with rapid adverse disease transformation and this further suggests that MDS-MSCs may be an integral part of disease progression and have prognostic value as well as potential as a therapeutic target.
Fibroblast growth factor 21 predicts outcome in community-acquired pneumonia: secondary analysis of two randomised controlled trials
Authors: Fahim Ebrahimi, Carole Wolffenbuttel, Claudine A. Blum, Christine Baumgartner, Beat Mueller, Philipp Schuetz, Christian Meier, Marius Kraenzlin, Mirjam Christ-Crain, Matthias Johannes Betz
Journal: European Respiratory Journal (2018)

Acute systemic inflammatory conditions are accompanied by profound alterations of metabolism. However, the role of fibroblast growth factor 21 (FGF21), a recently identified central regulator of metabolism, is largely unknown in community-acquired pneumonia (CAP). This study aims to characterise the pattern of FGF21 in pneumonia and associations with disease severity and outcome. This is a secondary analysis of two independent multicentre randomised controlled trials in patients presenting to the emergency department with CAP. Primary and secondary efficacy parameters included 30-day mortality, length of hospital stay, time to clinical stability and duration of antibiotic treatment. A total of 509 patients were included in the analysis. FGF21 levels at admission strongly correlated with disease severity, as measured by the Pneumonia Severity Index. Increased levels of FGF21 were associated with prolonged time to clinical stability, antibiotic treatment and hospitalisation. FGF21 levels at admission were significantly higher in nonsurvivors than in survivors, yielding a 1.61-fold increased adjusted odds ratio of 30-day mortality (95% CI 1.21–2.14; p=0.001). Moreover, FGF21 was found to identify patients for 30-day mortality with superior discriminative power compared with routine diagnostic markers. Moderate-to-severe CAP patients with higher levels of FGF21 were at increased risk for clinical instability, prolonged hospitalisation and 30-day all-cause mortality.
Abstract 19204: Characteristics of Chest Compressions Immediately Before and After Interruptions During Pediatric In-hospital CPR
Authors: Dana E Niles, Jordan Duval-Arnould, Ryan W Morgan, Tia Raymond, Pricilla Yu, Dianne Atkins, Stu Friess, Elaine Gilfoyle, Denise Welsby, Matthew Braga, Annemarie Silver, Vinay M Nadkarni
Journal: Circulation (2017)

Introduction: High-quality CPR, with chest compressions (CC) of optimal rate and depth, improves cardiac arrest survival. CPR quality has not been characterized immediately before and after interru...
Response to: ‘Mandatory, cost-driven switching from originator etanercept to its biosimilar SB <sub>4</sub> : possible fallout on non-medical switching’ by Cantini and Benucci
Authors: Bente Glintborg, Anne Gitte Loft, Emina Omerovic, Oliver Hendricks, Asta Linauskas, Jakob Espesen, Kamilla Danebod, Dorte Vendelbo Jensen, Henrik Nordin, Emil Barner Dalgaard, Stavros Chrysidis, Salome Kristensen, Johnny Lillelund Raun, Hanne Lindegaard, Natalia Manilo, Susanne Højmark Jakobsen, Inger Marie Jensen Hansen, Dorte Dalsgaard Pedersen, Inge Juul Sørensen, Lis Smedegaard Andersen, Jolanta Grydehøj, Frank Mehnert, Niels Steen Krogh, Merete Lund Hetland
Journal: Annals of the Rheumatic Diseases (2018)

Thank you for the interest in our publication based on data from the Danish DANBIO registry regarding 2061 patients who were eligible for a mandatory non-medical switch from originator to biosimilar etanercept in routine care.1 2 The marketing of biosimilars has changed the landscape of the biological drugs with the potential for huge cost reductions, most markedly if patients may be switched from an ongoing successful treatment with the expensive originator to a much cheaper biosimilar. Thus, up to 75% price reduction has been experienced in Denmark so far with no evidence of increased use of health resources.3 The outcomes of a non-medical switch of etanercept in the real-world setting are, however, largely unknown, since prevous publications on switching in routine care have included limited numbers of patients. The aim of the study was therefore to investigate the effectiveness of a large-scale, …
Polyomaviruses of the skin: integrating molecular and clinical advances in an emerging class of viruses
Authors: J.C. Sheu, J. Tran, P.L. Rady, H. Dao, S.K. Tyring, H.P. Nguyen
Journal: British Journal of Dermatology (2018)

Human polyomaviruses (HPyVs) are small, nonenveloped, double‐stranded DNA viruses that express tumour antigen proteins. Fourteen species of polyomaviruses have been discovered in humans, and since the 2008 discovery of the first cutaneous polyomavirus – Merkel cell polyomavirus (MCPyV) – six more species have been detected in the skin: trichodysplasia spinulosa‐associated polyomavirus (TSPyV), HPyV6, HPyV7, HPyV9, HPyV10 and HPyV13. Of these cutaneous species, only MCPyV, TSPyV, HPyV6 and HPyV7 have been definitively associated with diseases of the skin, most commonly in immunocompromised individuals. MCPyV is a predominant aetiology in Merkel cell carcinomas. TSPyV is one of the aetiological factors of trichodysplasia spinulosa. HPyV6 and HPyV7 have been recently linked to pruritic skin eruptions. The roles of HPyV9, HPyV10 and HPyV13 in pathogenesis, if any, are still unknown, but their molecular features have provided some insight into their functional biology. In this review, we summarize the known molecular mechanisms, clinical presentation and targeted therapies of each of the eight cutaneous HPyVs. We hope that heightened awareness and clinical recognition of HPyVs will lead to increased reports of HPyV‐associated diseases and, consequently, a more robust understanding of how to diagnose and treat these conditions.