tbuckley/cabot-search huggingface dataset:
AB0429 No difference in effectiveness with either etanercept originator or biosimilar as first line biologic treatment for rheumatoid arthritis
Authors: D. De Cock, R. Davies, L. Kearsley-Fleet, K. Watson, K. Hyrich
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Biosimilars and their reference agents have been shown to be equivalent in clinical trials. In the United Kingdom, etanercept biosimilars (ETA-B) are, since 2016, a first-line treatment option for the management of severe rheumatoid arthritis (RA) defined as no response to 2 or more csDMARDs. However, real world data, including how it compares to the etanercept originator (ETA-O) are lacking. <h3>Objectives</h3> This study aims to compare the short-term effectiveness of etanercept originator with its biosimilar in patients with RA when used as a first biologic following csDMARDs. <h3>Methods</h3> This study included patients with RA registered with the British Society for Rheumatology Biologics Registers for RA (BSRBR-RA) at the point of starting either ETA-O or an ETA-B since 2011 as their first biologic. Baseline information is collected at drug start and includes demographic and clinical data. Follow-up (FU) data are captured every 6 months and include details on therapy changes, current disease activity, and development of any adverse events. The primary outcome of this study is effectiveness as calculated by change in the 28 joint count disease activity score (DAS28). Only patients with a complete DAS28 at baseline and their 1st FU were included in the final analysis of this study. Hazard ratios (HR) comparing drug survival and risk of first serious adverse event (SAE) between ETA-O and ETA-B patients were calculated using Cox regression. <h3>Results</h3> Between January 2010 and 11 December 2017, 1217 and 412 patients starting ETA-O or ETA-B respectively were recruited and had ≥1 FU available. Complete DAS28 data at baseline and 1st FU were available for 740 ETA-O patients and 177 ETA-B patients. Patient characteristics were similar between the 2 cohorts (Table). After adjusting for baseline differences, no difference between groups was seen in DAS28 (p=0.1) or remission status (p=0.1) at 1st FU. Nine (5%) and 48 (6%) of ETA-B and ETA-O patients had stopped their respective treatments by the 1st FU. The adjusted hazard ratio for stopping ETA-O versus ETA-B over this time period was similar (HR=0.8 (0.4-1.6); p=0.5). Risk of SAEs over the first 6 months was also similar between groups (HR (ETA-B versus ETA-O) =0.6 (0.3-1.1); p=0.1), with 10 (6%) and 73 (10%) SAEs reported in ETA-B and ETA-O patients respectively until 1st FU. <h3>Conclusions</h3> In the UK, etanercept biosimilars are now frequently used as first-line biologics in RA patients. These short-term follow-up data demonstrate in routine clinical care that ETA-B appears to be equivalent to ETA-O in terms of short term effectiveness, drug survival and safety. <h3>Disclosure of Interest</h3> None declared
Successful treatment of large transformed mycosis fungoides with gemcitabine monotherapy
Authors: Hiroaki Asai, Kazuto Takeuchi, Yuuichi Ikeda, Toshiki Ochi, Kazushi Tanimoto, Jun Yamanouchi, Taichi Azuma, Hiroshi Fujiwara, Takaaki Hato, Masaki Yasukawa, Yoshihiro Yakushijin
Journal: Annals of Oncology (2018)
Abstract 14201: Long Term Outcomes of Mechanical Mitral Valve Replacement in Children: A Study From the Pediatric Cardiac Care Consortium
Authors: Chizitam Francis Ibezim, Noor Alshami, Jessica Knight, Omar Qayum, Amber Leila Sarvestani, Elizabeth Turk, Stephen Simon, Lazaros K Kochilas, James St. Louis, Geetha Raghuveer
Journal: Circulation (2017)

Background: Congenital mitral valve disease in children is recalcitrant and often not amenable to primary repair, thus, frequently requiring valve replacement. Long-term outcomes in those requiring...
Influence of enteral nutrition on nutritional status, treatment toxicities, and short-term outcomes in esophageal carcinoma patients treated with concurrent chemoradiotherapy: A prospective, multicenter, randomized controlled study
Authors: T. Li, J. Lyu, G. Zhu, J. Li, R. Zhao, S. Zhu, J. Wang, L. Xing, D. Yang, C. Xie, L.-F. Shen, H.-P. Shi, J. Lang
Journal: Annals of Oncology (2018)
Correlation between SARC-F and IADL score in breast cancer patients: a preliminary study
Authors: Felix Wijovi, Helenia Putri, Cindy M. Agatha, Cindy Virliani, Nadya N. Evangelista, Ongky Satria, Paulus S.B. Ringoringo, Andree Kurniawan
Journal: Annals of Oncology (2018)
Neuroinflammation, oxidative stress, and blood-brain barrier (BBB) disruption in acute Utah electrode array implants and the effect of deferoxamine as an iron chelator on acute foreign body response
Authors: Cassie Bennett, Farrah Mohammed, Anabel Álvarez-Ciara, Michelle A. Nguyen, W. Dalton Dietrich, Suhrud M. Rajguru, Wolfgang J. Streit, Abhishek Prasad
Journal: Biomaterials (2018)
Interim results from a phase I trial of SL-801: A novel XPO-1 inhibitor, in patients with advanced solid tumors
Authors: T.M. Bauer, M. Barve, E.G. Chiorean, P. Lorusso, K. Courtney, D. Qi, A. Olguin, J. Bullington, M. Sardone, V. Dunn, S. Shemesh, J. Chen, C. Brooks, J. Wang
Journal: Annals of Oncology (2018)
Government cracks down on prescription fraud
Authors: Gareth Iacobucci
Journal: BMJ (2018)

Patients who get free NHS prescriptions in England will face checks by pharmacists as part of a major government crackdown on fraud. Ministers estimate that prescription fraud costs the NHS £256m (€290m; $340m) a year and have set a target to halve this by 2020.

To help achieve this, a new digital system will be piloted in England next year to allow pharmacists to check instantly whether patients are entitled to a free prescription. If the pilot is successful, the government will extend the scheme across England, which …
Phase IV, open-label, multicentre trial of afatinib in patients (pts) aged ≥70 yrs with NSCLC harbouring common (Del19/L858R) EGFR mutations: Preliminary results
Authors: K.L. Reckamp, P. Gilman, B. Halmos, M. Jahanzeb, J. McCann, H. Paripati, L.C. Seneviratne, J.A. Wallace, B. Rueter, A. Esler, E. Dowling, M. Koczywas
Journal: Annals of Oncology (2018)
Lancet Commission on the Value of Death
Authors: Richard Smith, Jane Blazeby, Tracey Bleakley, Jocalyn Clark, Yali Cong, Robin Durie, Eric Finkelstein, Nahla Gafer, Sam Gugliani, Richard Horton, Malcolm Johnson, Celia Kitzinger, Jenny Kitzinger, Felicia Knaul, Arnoldo Kraus, Julia Neuberger, Mark O'Connell, Seamus O'Mahony, MR Rajagopal, Eriko Sase, Sheldon Solomon, Richard Smith, Ros Taylor, Katrina Wyatt
Journal: The Lancet (2018)
A Novel Nomogram to Identify Candidates for Extended Pelvic Lymph Node Dissection Among Patients with Clinically Localized Prostate Cancer Diagnosed with Magnetic Resonance Imaging-targeted and Systematic Biopsies
Authors: Giorgio Gandaglia, Guillaume Ploussard, Massimo Valerio, Agostino Mattei, Cristian Fiori, Nicola Fossati, Armando Stabile, Jean-Baptiste Beauval, Bernard Malavaud, Mathieu Roumiguié, Daniele Robesti, Paolo Dell’Oglio, Marco Moschini, Stefania Zamboni, Arnas Rakauskas, Francesco De Cobelli, Francesco Porpiglia, Francesco Montorsi, Alberto Briganti
Journal: European Urology (2018)
LURET: Final survival results of the phase II trial of vandetanib in patients with advanced RET-rearranged non-small cell lung cancer
Authors: K. Yoh, T. Seto, M. Satouchi, M. Nishio, N. Yamamoto, H. Murakami, N. Nogami, S. Kuroda, S. Nomura, A. Sato, K. Tsuchihara, T. Kohno, S. Matsumoto, K. Goto
Journal: Annals of Oncology (2018)
High ligation of the anal fistula tract by lateral approach: A prospective cohort study on a modification of the ligation of the intersphincteric fistula tract (LIFT) technique
Authors: Wook Ho Kang, Hyung Kyu Yang, Han Jeong Chang, Yong Taek Ko, Byung Eun Yoo, Cheong Ho Lim, Jae Kwan Hwang, Young Chan Lee, Hyeon Keun Shin, Hae Jung Son
Journal: International Journal of Surgery (2018)
Procalcitonin-guided antibiotic prescribing did not reduce antibiotic use in suspected LRTI in the ED
Authors: Giannoula S. Tansarli, Eleftherios Mylonakis
Journal: Annals of Internal Medicine (2018)

ACP Journal Club16 October 2018Procalcitonin-guided antibiotic prescribing did not reduce antibiotic use in suspected LRTI in the EDGiannoula S. Tansarli, MD, Eleftherios Mylonakis, MD, PhD, FIDSAGiannoula S. Tansarli, MDWarren Alpert Medical School of Brown University, Providence, Rhode Island, USA (G.S.T., E.M.)Search for more papers by this author, Eleftherios Mylonakis, MD, PhD, FIDSAWarren Alpert Medical School of Brown University, Providence, Rhode Island, USA (G.S.T., E.M.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/ACPJC-2018-169-8-039 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Source CitationHuang DT, Yealy DM, Filbin MR, et al; ProACT Investigators. Procalcitonin-guided use of antibiotics for lower respiratory tract infection. N Engl J Med. 2018;379:236-49. https://pubmed.ncbi.nlm.nih.gov/29781385Clinical Impact RatingsGIM/FP/GP: Emergency Med: Hospitalists: Infectious Disease: Pulmonology: Reference1 Schuetz P, Wirz Y, Sager R, et al. Procalcitonin to initiate or discontinue antibiotics in acute respiratory tract infections. Cochrane Database Syst Rev. 2017;10:CD007498. [PMID: 29025194] Google Scholar Author, Article, and Disclosure InformationAffiliations: Warren Alpert Medical School of Brown University, Providence, Rhode Island, USA (G.S.T., E.M.)This article was published at Annals.org on 2 October 2018. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 16 October 2018Volume 169, Issue 8Page: JC39KeywordsAdverse eventsAntibioticsAntimicrobialsBloodBlood groupsEmergency departmentLower respiratory tract infectionsPneumoniaSafety ePublished: 16 October 2018 Issue Published: 16 October 2018 Copyright & PermissionsCopyright © 2018 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Phase II study of resection of primary colorectal cancer and synchronous liver metastasis after S-1 + oxaliplatin (SOX) + bevacizumab (Bmab) therapy and adjuvant S-1 chemotherapy
Authors: T. Miura, H. Morohashi, Y. Sakamoto, T. Yoshida, K. Sato, K. Ishido, D. Kudo, N. Kimura, K. Hakamada
Journal: Annals of Oncology (2018)
Identification of Acute Kidney Injury Subphenotypes with Differing Molecular Signatures and Responses to Vasopressin Therapy
Authors: Pavan K. Bhatraju, Leila R. Zelnick, Jerald Herting, Ronit Katz, Carmen Mikacenic, Susanna Kosamo, Eric D. Morrell, Cassianne Robinson-Cohen, Carolyn S. Calfee, Jason D. Christie, Kathleen D. Liu, Michael A. Matthay, William O. Hahn, Victoria Dmyterko, Natalie S. J. Slivinski, Jim A. Russell, Keith R. Walley, David C. Christiani, W. Conrad Liles, Jonathan Himmelfarb, Mark M. Wurfel
Journal: American Journal of Respiratory and Critical Care Medicine (2018)

Currently, no safe and effective pharmacologic interventions exist for acute kidney injury (AKI). One reason may be that heterogeneity exists within the AKI population, thereby hampering the identification of specific pathophysiologic pathways and therapeutic targets.The aim of this study was to identify and test whether AKI subphenotypes have prognostic and therapeutic implications.First, latent class analysis methodology was applied independently in two critically ill populations (discovery [n = 794] and replication [n = 425]) with AKI. Second, a parsimonious classification model was developed to identify AKI subphenotypes. Third, the classification model was applied to patients with AKI in VASST (Vasopressin and Septic Shock Trial; n = 271), and differences in treatment response were determined. In all three populations, AKI was defined using serum creatinine and urine output.A two-subphenotype latent class analysis model had the best fit in both the discovery (P = 0.004) and replication (P = 0.004) AKI groups. The risk of 7-day renal nonrecovery and 28-day mortality was greater with AKI subphenotype 2 (AKI-SP2) relative to AKI subphenotype 1 (AKI-SP1). The AKI subphenotypes discriminated risk for poor clinical outcomes better than the Kidney Disease: Improving Global Outcomes stages of AKI. A three-variable model that included markers of endothelial dysfunction and inflammation accurately determined subphenotype membership (C-statistic 0.92). In VASST, vasopressin compared with norepinephrine was associated with improved 90-day mortality in AKI-SP1 (27% vs. 46%, respectively; P = 0.02), but no significant difference was observed in AKI-SP2 (45% vs. 49%, respectively; P = 0.99) and the P value for interaction was 0.05.This analysis identified two molecularly distinct AKI subphenotypes with different clinical outcomes and responses to vasopressin therapy. Identification of AKI subphenotypes could improve risk prognostication and may be useful for predictive enrichment in clinical trials.
GW29-e0910 Si-miao-yong-an decoction ameliorated cardiac function through restoring the equilibrium of SOD and NOX2 in heart failure mice
Authors: Yinglu Ren, Huimin Zhang, Zifan Zeng, Xuan Xie, Congping Su, Qing Wang, Wei Wang, Shuzhen Guo
Journal: Journal of the American College of Cardiology (2018)
Increased Reporting of Immune Checkpoint Inhibitor–Associated Diabetes
Authors: Jordan J. Wright, Joe-Elie Salem, Douglas B. Johnson, Bénédicte Lebrun-Vignes, Angeliki Stamatouli, James W. Thomas, Kevan C. Herold, Javid Moslehi, Alvin C. Powers
Journal: Diabetes Care (2018)

Immune checkpoint inhibitors (CPI) have proven remarkably effective in treating many types of malignancies but have been associated with significant risk for immune-related adverse events (irAEs) (1). Among these, new onset of insulin-dependent diabetes mellitus (DM) occurs in 0.2–1.0% of patients (2,3) and is being seen more frequently as CPI become more widely used. However, the incidence, clinical course, and pathogenesis of CPI-associated DM (CPI-DM) are not well understood.

To better understand the characteristics of CPI-DM, we analyzed VigiBase (4), the World Health Organization’s database of individual case safety reports, and detected 283 cases of new-onset DM from 2014 to April 2018 following treatment with CPI using the following preferred terms according to MedDRA (Medical Dictionary for Regulatory Activities): diabetic ketoacidosis (DKA), diabetic ketosis, type 1 diabetes mellitus, or fulminant type 1 diabetes mellitus; any one of these was sufficient to define CPI-DM. We noted a marked increase in reporting of CPI-DM over this time period, with over 50% of cases reported in 2017 (Table 1). Overall, half of the patients with DM presented in DKA (50.2%); 5.6% of all cases were also on steroids at diagnosis of DM, and 6.4% were on noninsulin diabetes medications in addition to insulin. …
Harnessing accurate non-homologous end joining for efficient precise deletion in CRISPR/Cas9-mediated genome editing
Authors: Tao Guo, Yi-Li Feng, Jing-Jing Xiao, Qian Liu, Xiu-Na Sun, Ji-Feng Xiang, Na Kong, Si-Cheng Liu, Guo-Qiao Chen, Yue Wang, Meng-Meng Dong, Zhen Cai, Hui Lin, Xiu-Jun Cai, An-Yong Xie
Journal: Genome biology (2018)

Many applications of CRISPR/Cas9-mediated genome editing require Cas9-induced non-homologous end joining (NHEJ), which was thought to be error prone. However, with directly ligatable ends, Cas9-induced DNA double strand breaks may be repaired preferentially by accurate NHEJ. In the repair of two adjacent double strand breaks induced by paired Cas9-gRNAs at 71 genome sites, accurate NHEJ accounts for about 50% of NHEJ events. This paired Cas9-gRNA approach underestimates the level of accurate NHEJ due to frequent + 1 templated insertions, which can be avoided by the predefined Watson/Crick orientation of protospacer adjacent motifs (PAMs). The paired Cas9-gRNA strategy also provides a flexible, reporter-less approach for analyzing both accurate and mutagenic NHEJ in cells and in vivo, and it has been validated in cells deficient for XRCC4 and in mouse liver. Due to high frequencies of precise deletions of defined "3n"-, "3n + 1"-, or "3n + 2"-bp length, accurate NHEJ is used to improve the efficiency and homogeneity of gene knockouts and targeted in-frame deletions. Compared to "3n + 1"-bp, "3n + 2"-bp can overcome + 1 templated insertions to increase the frequency of out-of-frame mutations. By applying paired Cas9-gRNAs to edit MDC1 and key 53BP1 domains, we are able to generate predicted, precise deletions for functional analysis. Lastly, a Plk3 inhibitor promotes NHEJ with bias towards accurate NHEJ, providing a chemical approach to improve genome editing requiring precise deletions. NHEJ is inherently accurate in repair of Cas9-induced DNA double strand breaks and can be harnessed to improve CRISPR/Cas9 genome editing requiring precise deletion of a defined length.
THU0489 The impact of calcium intake and physical exercise on peak bone mineral density
Authors: L. Brites, M.L. Marques, A. Marques, A. Daniel, M. Santiago, J. Pereira da Silva
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Regular exercise and adequate nutrition are frequently prescribed as strategies to optimise peak bone mass and maintain bone and muscle health throughout life. <h3>Objectives</h3> The aim of our work was to determine the relationship of clinically assessed milk intake and physical exercise with bone mineral density (BMD) in young adults. <h3>Methods</h3> This cross-sectional study included members of the general population aged between 20 and 30 years from the Portuguese cohort SAOL (individuals aged 18+years randomly selected from a local county of Coimbra, Portugal). No exclusion criteria were applied. Individuals were asked to describe their milk intake (up to 2 glass/day and 2+glass/day, corresponding to up to and more than 480 mg/day), regular physical activity (categorised as none-to-moderate and at least intense physical activity) and strenuous sports practice (up to 2 hour/week and 2+hour/week) from the age of 10 to 25. They underwent a Dual-energy x-ray absorptiometry (DEXA) of the lumbar spine (LS) and proximal femur (PF). Categorical data is presented as proportions/percentages and continuous variable as median ±standard deviation. Differences between groups were assessed by Mann–Whitney U test. Potential predictors of a higher BMD of PF and LS were identified using multiple linear regression analysis. P-values&lt;0.05 were considered statistically significant. <h3>Results</h3> We included 259 individuals (mean age of 24.7±2.7 years, 60.6% being female). The majority (82.6%), described having a moderate regular physical activity (equivalent to working as a mailman), practicing strenuous sports at least 2 hours per week (81.1%) and ingesting at least two glasses of milk per day (83.4%). The current BMD of the PF and LS were 0.8±0.13 and 0.99±0.11, respectively. On univariate analysis, the only significant association related the PF BMD and milk intake (p=0.008). Multiple linear regression analysis showed that while physical activity and sports practice did not predict BMD values, milk intake persisted as a predictor of a higher BMD of PF (p=0.022), even after including other explanatory variables. No statistically significant predictors were found for BMD of the LS. <h3>Conclusions</h3> Our study showed that clinically assessed milk intake between the ages of 10 and 25 years, but not physical exercise, is a significant predictor of higher bone mineral density assessed by DEXA at the PF. These results do not exclude a positive impact of exercise upon peak bone mass, but suggest that its retrospective evaluation in a clinical setting should not be taken as reassurance that a good peak bone mass was achieved in early adulthood. <h3>Disclosure of Interest</h3> None declared
Abstract P145: The Effects of Phosphorus Additives on Albuminuria and Fibroblast Growth Factor-23
Authors: Alex Chang, Edgar Miller, Cheryl Anderson, Melissa Moser, Jeanne Charleston, Karen White, Bobbie Henry, Susan Oh, Lawrence Appel, Stephen Juraschek
Journal: Circulation (2016)

Background: Phosphorus-based additives are prevalent in processed foods. Their effects on cardiovascular and renal health are unknown. Methods: We conducted a randomized, double-blind, cross-over study to examine the effects of phosphorus additives on albuminuria and fibroblast growth factor-23 (FGF-23) in adults with microalbuminuria and estimated glomerular filtration rate (eGFR) ≥ 45 ml/min/1.73m2. Participants (n=31) received unaltered beverages and breakfast bars (with or without phosphorus additives; 941 mg/d contrast in phosphorus) for 3 week periods, separated by a 2-4 week washout period. Diet was assessed by 24-hour recalls bi-weekly. Primary outcomes were albuminuria and FGF-23 assessed by two 24-hour urine collections and a single fasting blood draw at the end of each period. Results: We included 31 participants (32% female, 90% black, 87% hypertension, 48% diabetes) with mean age, eGFR, and 24-hour urine albumin excretion of 66 years, 68 ml/min/1.73m2, and 74.4 mg/d, respectively. Mean self-reported phosphorus intake and 24-hour urine phosphorus excretion was 1113 mg/d and 687.9 mg/d at baseline. Self-reported phosphorus intake (excluding intervention products) decreased by 151 mg/d (p=0.004) during the phosphorus additive period compared to the non-phosphorus additive period as did protein intake (8.0 g/d lower, p=0.02). In unadjusted analyses, consumption of phosphorus additives increased 24-hour urine phosphorus excretion by a mean of 505 mg/d, non-significantly increased albuminuria by 14.3% (95% CI: -2.5% to 34.0%, p=0.1), but had no effect on FGF-23 (3.0%, 95% CI: -9.3% to 16.8%). After adjustment for changes in weight and self-reported dietary intake (sodium, phosphorus, and protein intake), consumption of phosphorus additives increased albuminuria by 22.5% (95% CI: 3.1% to 45.6%, p=0.02). In unadjusted analysis excluding two patients non-compliant with the intervention, consumption of phosphorus additives increased albuminuria by 17.3% (95% CI: 0.08% to 37.5%, p=0.049). Neither sensitivity analysis showed an effect on FGF-23. Conclusion: High consumption of phosphorus-based additives may increase albuminuria. Further studies are needed to confirm this finding and determine the long-term effects on cardiovascular and renal health.
A Randomized Trial of Rapamycin to Increase Longevity and Healthspan in Companion Animals: Navigating the Boundary Between Protections for Animal Research and Human Subjects Research
Authors: Holly A. Taylor, Christian Morales, Liza-Marie Johnson, Benjamin S. Wilfond
Journal: The American Journal of Bioethics (2018)

"A Randomized Trial of Rapamycin to Increase Longevity and Healthspan in Companion Animals: Navigating the Boundary Between Protections for Animal Research and Human Subjects Research." The American Journal of Bioethics, 18(10), pp. 58–59