tbuckley/cabot-search huggingface dataset:
Topical Combination of Fluorouracil and Calcipotriene as a Palliative Therapy for Refractory Extramammary Paget Disease
Authors: Gabriel E. Molina, Saami Khalifian, Jamie L. Mull, Lu Chen, Ilana S. Rosman, Beverly E. Faulkner-Jones, Kenneth H. Ngo, Shadmehr Demehri, Lynn A. Cornelius, Peggy A. Wu
Journal: JAMA Dermatology (2019)

Extramammary Paget disease (EMPD), a rare intraepithelial adenocarcinoma, poses a therapeutic challenge with high postoperative recurrence rates and a limited number of effective local treatment options.To describe the use and efficacy of a topical combination of fluorouracil and calcipotriene as a palliative therapy for refractory EMPD.This retrospective case series of 3 women with recurrent, refractory EMPD was conducted at Beth Israel Deaconess Medical Center, Boston, Massachusetts and Washington University School of Medicine, St Louis, Missouri. All patients were treated with a 1:1 mixture of fluorouracil, 5%, cream and calcipotriene, 0.005%, cream or ointment.Clinical and histopathological findings.All 3 women (1 in her 50s, 2 in their 70s) presented with recurrent EMPD (vulvar, perianal, and perioral) after surgery and/or irradiation, and their EMPD was refractory to treatment with imiquimod, 5%, cream. Owing to disease progression and/or intolerable adverse effects from imiquimod, the patients began treatment with a 1:1 mixture of fluorouracil, 5%, cream and calcipotriene, 0.005%, cream. This treatment, which was well tolerated, was followed by clinical improvement in symptoms and appearance of the lesions in all 3 cases and histopathological signs of decreased tumor burden in 2 cases. Patients applied the combination topical therapy to affected areas with differing frequencies, ranging from 1 to 2 days per month to 4 consecutive days every 2 weeks.Extramammary Paget disease frequently recurs even after aggressive surgical management and can be refractory to many topical and locoregional therapies. Palliative treatment with a combination of fluorouracil and calcipotriene may be a viable option for patients with recurrent, refractory EMPD.
Evaluation of Glomerular Hemodynamic Function by Empagliflozin in Diabetic Mice Using In Vivo Imaging
Authors: Kengo Kidokoro, David Z.I. Cherney, Andrea Bozovic, Hajime Nagasu, Minoru Satoh, Eiichiro Kanda, Tamaki Sasaki, Naoki Kashihara
Journal: Circulation (2019)

Background: Sodium glucose cotransporter 2 inhibitors may reduce kidney hyperfiltration, thereby preventing diabetic kidney disease progression, which may in turn reduce cardiovascular risk, including heart failure. However, the mechanisms that regulate renal function responses to sodium glucose cotransporter 2 inhibition are not yet fully understood. We explored the renal protective effects of sodium glucose cotransporter 2 inhibition with empagliflozin, with a focus on glomerular hemodynamic effects and tubuloglomerular feedback using in vivo multiphoton microscopy imaging techniques. Methods: C57BL/6 mice and spontaneously diabetic Ins2 +/Akita mice were studied. The mice were treated with empagliflozin (20 mg·kg –1 ·d –1 ) and insulin for 4 weeks, and the single-nephron glomerular filtration rate was measured using multiphoton microscope. A neuronal nitric oxide synthase inhibitor (7-nitroindazole, 20 mg·kg –1 ·d –1 ) or a cyclooxygenase-2 inhibitor (SC58236, 6 mg/L), or an A1 adenosine receptor antagonist (8-cyclopentyl-1,3-dipropylxanthine, 1 mg·kg –1 ·d –1 ) was administered to elucidate the mechanisms of tubuloglomerular feedback signaling and single-nephron glomerular filtration rate regulation. Results: The urinary excretion of adenosine, nitric oxide metabolites, and the prostanoid prostaglandin E2 was also quantified. The single-nephron glomerular filtration rate in the Ins2 +/Akita group was higher than in controls (C57BL/6; 4.9±1.3 nL/min versus Ins2 +/Akita ; 15.8±6.8 nL/min) and lower in Ins2 +/Akita /empagliflozin to 8.0±3.3 nL/min ( P &lt;0.01). In vivo imaging also revealed concomitant afferent arteriolar dilation ( P &lt;0.01) and increased glomerular permeability of albumin in the Ins2 +/Akita group. Empagliflozin ameliorated these changes ( P &lt;0.01). Urinary adenosine excretion in the Ins2 +/Akita /empagliflozin group was higher than in Ins2 +/Akita ( Ins2 +/Akita ; 3.4±1.4 nmol/d, Ins2 +/Akita /empagliflozin; 11.2±3.0 nmol/d, P &lt;0.05), whereas nitric oxide metabolites and prostaglandin E2 did not differ. A1 adenosine receptor antagonism, but not neuronal nitric oxide synthase or cyclooxygenase-2 inhibition, blocked the effect of empagliflozin on renal function. Empagliflozin increased urinary adenosine excretion and reduced hyperfiltration via afferent arteriolar constriction, effects that were abolished by A1 adenosine receptor blockade. Conclusions: Adenosine/A1 adenosine receptor pathways play a pivotal role in the regulation of the single-nephron glomerular filtration rate via tubuloglomerular feedback mechanisms in response to sodium glucose cotransporter 2 inhibition, which may contribute to renal and cardiovascular protective effects reported in clinical trials.
SP0223 Lessons Learnt from Recent MRI Trials in RA
Authors: J. Baker
Journal: Annals of the Rheumatic Diseases (2015)

Given the limitations of clinical composite measures to quantify disease activity in rheumatoid arthritis (RA) and limitations of standard x-rays in quantifying structural joint damage, it is important to consider imaging biomarkers that may provide a more complete and more objective portrayal of the disease process. Objective tools may be more sensitive to change and may more easily discriminate between ineffective and effective therapies. The conduct of clinical trials in RA is highly costly, partly due to the large sample sizes necessary to discriminate effective therapies compared to improving standards of care. Methodologies that can quantify the inflammatory disease burden accurately and with greater sensitivity to change have the potential to reduce sample sizes and study duration and to improve our understanding of the biologic effects of new therapies. A number of trial designs have now incorporated MRI and demonstrated that MRI measures 1) correlate with component indices of clinical disease activity, 2) can accurately assess changes in inflammatory disease burden and structural damage progression related to treatment effects, 3) can predict later radiographic outcomes, and 4) could improve discrimination of effective therapies and reduce sample sizes. There is therefore substantial evidence that MRI would be a reliable as a clinical trial endpoint and would substantially improve study power and reduce required sample sizes and thereby cost. Remaining questions are how to combine MRI with other disease assessments and whether this modality adequately reflects the patient experience to be used as a primary clinical trial endpoint. <h3>Disclosure of Interest</h3> None declared
Patient relevant outcomes of unicompartmental versus total knee replacement: systematic review and meta-analysis
Authors: Hannah A Wilson, Rob Middleton, Simon G F Abram, Stephanie Smith, Abtin Alvand, William F Jackson, Nicholas Bottomley, Sally Hopewell, Andrew J Price
Journal: BMJ (2019)

Abstract Objective To present a clear and comprehensive summary of the published data on unicompartmental knee replacement (UKA) or total knee replacement (TKA), comparing domains of outcome that have been shown to be important to patients and clinicians to allow informed decision making. Design Systematic review using data from randomised controlled trials, nationwide databases or joint registries, and large cohort studies. Data sources Medline, Embase, Cochrane Controlled Register of Trials (CENTRAL), and Clinical Trials.gov, searched between 1 January 1997 and 31 December 2018. Eligibility criteria for selecting studies Studies published in the past 20 years, comparing outcomes of primary UKA with TKA in adult patients. Studies were excluded if they involved fewer than 50 participants, or if translation into English was not available. Results 60 eligible studies were separated into three methodological groups: seven publications from six randomised controlled trials, 17 national joint registries and national database studies, and 36 cohort studies. Results for each domain of outcome varied depending on the level of data, and findings were not always significant. Analysis of the three groups of studies showed significantly shorter hospital stays after UKA than after TKA (−1.20 days (95% confidence interval −1.67 to −0.73), −1.43 (−1.53 to −1.33), and −1.73 (−2.30 to −1.16), respectively). There was no significant difference in pain, based on patient reported outcome measures (PROMs), but significantly better functional PROM scores for UKA than for TKA in both non-trial groups (standard mean difference −0.58 (−0.88 to −0.27) and −0.29 (−0.46 to −0.11), respectively). Regarding major complications, trials and cohort studies had non-significant results, but mortality after TKA was significantly higher in registry and large database studies (risk ratio 0.27 (0.16 to 0.45)), as were venous thromboembolic events (0.39 (0.27 to 0.57)) and major cardiac events (0.22 (0.06 to 0.86)). Early reoperation for any reason was higher after TKA than after UKA, but revision rates at five years remained higher for UKA in all three study groups (risk ratio 5.95 (1.29 to 27.59), 2.50 (1.77 to 3.54), and 3.13 (1.89 to 5.17), respectively). Conclusions TKA and UKA are both viable options for the treatment of isolated unicompartmental osteoarthritis. By directly comparing the two treatments, this study demonstrates better results for UKA in several outcome domains. However, the risk of revision surgery was lower for TKA. This information should be available to patients as part of the shared decision making process in choosing treatment options. Systematic review registration PROSPERO number CRD42018089972.
Loss of KDM6A Confers Drug Resistance in Acute Myeloid Leukemia
Authors: Sophie M. Stief, Anna-Li Hanneforth, Raphael Mattes, Sabrina Weser, Binje Vick, Michael D. Bartoschek, Helena Domínguez Moreno, Wen-Hsin Liu, Bianka Ksienzyk, Maja Rothenberg-Thurley, Hilmar Quentmeier, Wolfgang Hiddemann, Klaus H. Metzeler, Gunnar Schotta, Sebastian Bultmann, Irmela Jeremias, Heinrich Leonhardt, Karsten Spiekermann
Journal: Blood (2018)
Extrafine triple therapy in patients with symptomatic COPD and history of one moderate exacerbation
Authors: Dave Singh, Leonardo M. Fabbri, Massimo Corradi, George Georges, Alessandro Guasconi, Stefano Vezzoli, Stefano Petruzzelli, Alberto Papi
Journal: European Respiratory Journal (2019)

<b>In patients with symptomatic COPD, severe/very severe airflow limitation, and a history of one moderate (and no severe) exacerbation, ICS-containing triple therapy significantly reduces exacerbation risk overall <i>versus</i> single or double maintenance therapy</b>http://ow.ly/VgJC30o9pXC
ACC/AHA/ESC 2006 Guidelines for the Management of Patients With Atrial Fibrillation
Authors: Valentin Fuster, Lars E. Rydén, David S. Cannom, Harry J. Crijns, Anne B. Curtis, Kenneth A. Ellenbogen, Jonathan L. Halperin, Jean-Yves Le Heuzey, G. Neal Kay, James E. Lowe, S. Bertil Olsson, Eric N. Prystowsky, Juan Luis Tamargo, Samuel Wann
Journal: Journal of the American College of Cardiology (2006)
Acute dual antiplatelet therapy for minor ischaemic stroke or transient ischaemic attack
Authors: Yongjun Wang, S Claiborne Johnston, Philip M Bath, James C Grotta, Yuesong Pan, Pierre Amarenco, Yilong Wang, Tabassome Simon, Jong Sung Kim, Jiann-Shing Jeng, Liping Liu, Yi Lin, Ka Sing Lawrence Wong, David Wang, Hao Li
Journal: BMJ (2019)

Recent research on antiplatelet therapy has advanced the knowledge of early, intensive treatment for recurrent stroke in minor ischaemic stroke or transient ischaemic attack Recent trialsIn the past five years, trials on acute antiplatelet treatment have focused on evaluating the efficacy and safety of more intensive treatment to prevent recurrent stroke after minor ischaemic stroke or high risk transient ischaemic attack.These include dual therapy versus monotherapy, 1 2 triple versus dual antiplatelet treatment, 10 and a potentially more potent agent (ticagrelor)
Abstract 3120: Functional characterization of ERCC1 isoforms in NSCLC
Authors: Luc Friboulet, Juergen Thomale, Ken Olaussen, Florence Ponsonnailles, Nicolas Dorvault, Frederic Commo, Patrick Saulnier, Stephan Vagner, Nader NAKOUZI, Fabrice André, Jean-Charles Soria
Journal: Cancer Research (2012)

Abstract Background: ERCC1 is a DNA repair protein whose expression is a prognostic and predictive biomarker of chemotherapy effect in NSCLC. Five alternative transcripts of the ERCC1 gene have been described or hypothesized to exist (isoforms 201 to 205). Nevertheless, little is known about the function and relative expression of these isoforms. We explored 3 main questions: a- Which ERCC1 isoforms are detected by clinically validated antibodies? b- Which isoforms are expressed in lung cancer cell lines and patient samples? c- Which isoforms are functional for removal of cisplatin DNA-adducts and potentially relevant as predictors of cisplatin resistance? Methods: To determine the specificity of anti-ERCC1 antibodies, a screening of isoform specific peptide sequences was achieved using a peptide array (Epitope Mapping CelluSpots™). The expression of ERCC1 isoforms was evaluated in 20 lung cancer cell lines and in 123 NSCLC patients by qRT-PCR. We established a functional DNA repair assay by monitoring the accumulation of cisplatin adducts over time with a specific antibody RC-18 (courtesy of Juergen Thomale, Germany). To investigate isoforms functionality, we created stable ERCC1 attenuated A549 cells with Zinc Finger Nucleases technology (Sigma). Using lentiviral constructs we rescued ERCC1 isoforms expression. Results: The 2 monoclonal antibodies, clone 8F1 and 3H11 recognize a conserved region shared by all isoforms of ERCC1 protein, and so, are unable to distinguish the different isoforms. The 5 isoforms were all detected at mRNA level, both in cancer cell lines and in patient tissues. Interestingly, a significant increase in isoform 201 expression was observed in all tumor tissues compared to normal counterparts. We obtained 7 A549 clones harboring a 85-95% decrease in ERCC1 expression. In these cells we observed a 7-fold increase in IC50 of cisplatin accompanied by a significant decrease in the rate of nucleotide excision repair (NER). We are currently exploring isoform function by analyzing DNA repair efficiency in the different stable cell lines. Conclusions: Alternative roles for ERCC1 beyond NER are currently emerging. Our 7 A549 clones, with stable and strong ERCC1 attenuation, provide a very promising tool to analyse all functions of ERCC1. Since most antibodies used to test ERCC1 positivity in patients do not distinguish the different isoforms, it is urgent to characterize their function further, particularly the role of isoform 201 overexpression in NSCLC tumors. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3120. doi:1538-7445.AM2012-3120
P150 Impact of radon SPA on pain and the immune system of patients with musculoskeletal disorders
Authors: I Becker, A-J Donaubauer, G Klein, C Fournier, R Fietkau, B Frey, US Gaipl
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Career situation of first and presenting author</h3> Post-doctoral fellow. <h3>Introduction</h3> The pain reducing effects of certain natural springs containing the radioactive noble gas radon have been described for centuries. Today, one expects that small cumulative dose of radiation of about 0.3 mSv originating from radon progeny impacts on the immune system and bone metabolism of patients suffering from chronic painful degenerative and/or inflammatory diseases. However, osteoimmunological analyses of patients during radon spa were lacking. <h3>Objectives</h3> We initiated the observational and explorative RAD-ON01 study to analyse for the first time the impact of radon spa on the immune status in the whole blood of 100 patients. <h3>Methods</h3> Whole blood of the patients was drawn before and at weeks 6, 12 and 30 after therapy. Deep immunophenotyping was performed by multicolour flow cytometry and cytokine analyses by ELISA. <h3>Results</h3> The RAD-ON01 study confirmed a long-lasting pain reduction. While the major immune cells were only marginally affected, in particular regulatory T cells and dendritic cells were temporarily increased and activation markers on immune cells were decreased. Further, a decrease of serum markers related to bone erosion was observed. The cytokine analyses showed that temporarily increased TGFβ following radon spa correlates with reduced pain perception of the patients. To exclude placebo effects, in November 2018 the RAD-ON02 study (EUDRACT: 2016-002085-31) started. With this prospective, temporarily placebo-controlled and double- blinded trial the evidence level of radon spa application and knowledge on osteoimmunological modes of action of radon should be improved. <h3>Conclusions</h3> We conclude that patients with musculoskeletal disorders do benefit from radon spa and that osteoimmunological mechanisms are modulated by exposure of the patients to very low doses of radiation. Future randomized studies should improve the evidence level for radon as therapeutic option for chronic painful degenerative and/or inflammatory diseases. <h3>Acknowledgements</h3> This work was supported by the German Federal Ministry of Education and Research (GREWIS, 02NUK017G and GREWIS-alpha, 02NUK050E), the Bayerisches Staatsbad Bad Steben GmbH, the Landesamt für Gesundheit und Lebensmittelsicherheit Bayern, and the EU (FP7 Nuclear Fission, Safety and Radiation Protection; FP7–249689). <h3>Disclosure of Interest</h3> None declared.
P168 Prevalence and characteristics of cardiovascular risk factors and coronary disease among patients with psoriatic arthritis
Authors: N Plaza Aulestia, SA Rodriguez Montero, MJ Perez Quintana, ML Velloso Feijóo
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Career situation of first and presenting author</h3> Resident. <h3>Introduction</h3> Patients with psoriatic arthritis have increased cardiovascular disease risk and comorbidity compared with the general population. <h3>Objectives</h3> To describe prevalence and characteristics of coronary disease and cardiovascular risk factor in a cohort of patients with psoriatic arthritis over 40 years old, in each group of treatment (DMARDS vs biologic therapy). <h3>Methods</h3> Patients older than 40 years old with psoriatic arthritis were identified based on medical records of Rheumatology department database. Primary outcomes included: age, sex, disease duration and age at the coronary event, HLAB27 positivity, hypertension, type II diabetes and hyperlipidemia. <h3>Results</h3> Of the 137 patients, 57% were men and mean age was 57.05±10.6 years old. 82% had only peripheral arthritis, while 18% also showed axial involvement. Regarding the latter subgroup, 16% of patients had a positive HLA-B27 test, 56% were HLA-B27 negative and 28% showed lack of the test. 87% of patients were in DMARDs therapy, while 31% received biologic therapy: etanercept 42%, secukinumab 16%, adalimumab 12%, ustekinumab 12%, infliximab 9,5%, golimumab 4,7% and certolizumab 2%. About 7% of patients didn´t receive DMARDS neither biologic therapy, because of intolerance. Prevalence for DMARD group and biologic group for hypertension was 43% and 26%, respectively; for diabetes 19,5% and 7%; hyperlipemia 47,5% and 38%; coronary disease 10,9% and 2,4%. In DMARD subgroup, we found 6 myocardial infarction (all of them revascularized) and 3 angina, versus 1 myocardial infarction in biologic subgroup <h3>Conclusions</h3> There is solid epidemiologic evidence linking PsA to cardiovascular risk factors and an increased risk of developing cardiovascular disease. In addition, over the past two decades it has become clear that chronic inflammation is an independent risk factor for cardiovascular events. In our study the ratio of ischemic heart disease for patients with PsA in DMARD therapy is four times higher than biologic treatment group. This may be due to the greater percentage of cardiovascular risk factors in the first group, although, the cardioprotective effect of biologic therapies, must be considered, as there are some studies that show association between antiTNF and significant reduction in carotid IMT. Proper management of cardiovascular risk requires aggressive control of disease activity. <h3>References</h3> <i>Int J Mol Sci</i> 2018;19(1):58. <i>Int J Rheumatol</i> 2012;2012:714321. <h3>Disclosure of Interest</h3> None declared.
The response to lymphodepletion impacts PFS in patients with aggressive non-Hodgkin lymphoma treated with CD19 CAR T cells
Authors: Alexandre V. Hirayama, Jordan Gauthier, Kevin A. Hay, Jenna M. Voutsinas, Qian Wu, Ted Gooley, Daniel Li, Sindhu Cherian, Xueyan Chen, Barbara S. Pender, Reed M. Hawkins, Aesha Vakil, Rachel N. Steinmetz, Utkarsh H. Acharya, Ryan D. Cassaday, Aude G. Chapuis, Tejaswini M. Dhawale, Paul C. Hendrie, Hans-Peter Kiem, Ryan C. Lynch, Jorge Ramos, Mazyar Shadman, Brian G. Till, Stanley R. Riddell, David G. Maloney, Cameron J. Turtle
Journal: Blood (2019)
Gain-of-function mutation of microRNA-140 in human skeletal dysplasia
Authors: Giedre Grigelioniene, Hiroshi I. Suzuki, Fulya Taylan, Fatemeh Mirzamohammadi, Zvi U. Borochowitz, Ugur M. Ayturk, Shay Tzur, Eva Horemuzova, Anna Lindstrand, Mary Ann Weis, Gintautas Grigelionis, Anna Hammarsjö, Elin Marsk, Ann Nordgren, Magnus Nordenskjöld, David R. Eyre, Matthew L. Warman, Gen Nishimura, Phillip A. Sharp, Tatsuya Kobayashi
Journal: Nature Medicine (2019)
A Leukemic Stem Cell Signature-Based Scoring System for Predicting Prognosis in Myelodysplastic Syndrome Patients
Authors: Yu-Hung Wang, Chien-Chin Lin, Chi-Yuan Yao, Cheng-Hong Tsai, Hsin-An Hou, Wen-Chien Chou, Hwei-Fang Tien
Journal: Blood (2018)
LG-23MicroRNA519d AND microRNA4758 IN DISTINGUISHING GANGLIOGLIOMA FROM DYSEMBRYOPLASTIC NEUROEPITHELIAL TUMORS AND ASTROCYTOMAS
Authors: Avanita S. Prabowo, Andrea Arena, Jasper J. Anink, Wim GM Spliet, Antoinette YN Schouten-van Meeteren, Anand M. Iyer, Eleonora Aronica
Journal: Neuro-Oncology (2016)
Utility of Cricoid Pressure
Authors: Arjang Khorasani, M. Ramez Salem, George J. Crystal
Journal: JAMA Surgery (2019)

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Protective Effects of Carbon Monoxide Delivered By Corm-401 in Hyperhemolysis in Patients with Sickle Cell Disease
Authors: Nguyen-Peyre Kim-Anh, Bodivit Gwellaouen, Foresti Roberta, Kiger Laurent, Gaetana Di Liberto, Philippe Chadebech, Alicia Jouard, Sadaf Pakdaman, Seguin Marion, Marden Micheal, France Pirenne, Motterlini Roberto, Pablo Bartolucci
Journal: Blood (2018)