tbuckley/cabot-search huggingface dataset:
AB0339 THE IMPORTANCE OF THERAPEUTIC COMPLIANCE: ADHERENCE TO METHOTREXATE AND ITS ROLE IN IMMUNOGENICITY
Authors: P. García, M. González Fernández, M. N. Rivas, J. Duruelo, E. Garmendia, J. Arostegui Lavilla, F. Perez-Ruiz, A. Alonso, C. Modesto, B. A. Blanco Cáceres
Journal: Annals of the Rheumatic Diseases (2020)

Background: Immunogenicity against adalimumab leads to loss of response and secondary failure to biologic therapy; however, concomitant use of methotrexate (MTX) seems to reduce the development of anti-drug antibodies (ADAbs) in a dose-dependent manner. Suboptimal adherence to MTX may favour ADAbs appearance. Objectives: To evaluate the relationship between MTX adherence and ADAbs development. Methods: Observational study among adult patients with chronic inflammatory arthropathy, followed in a tertiary care centre, who were in treatment with MTX and adalimumab. ADAbs formation in relation to MTX adherence was assessed. Results: 33 patients were included, with a MTX adherence overall mean of 82.13 (12.45%-100%, median adherence 92.19%). Only 9.09% (n=3) of the patients developed ADAbs, being its MTX adherence mean of 60.95% (46.47%-70%, median adherence 66.39%); ADAbs negative group showed an average MTX adherence of 84.23% (12.45%-100%, median adherence 94.29%). A statistically significant result (p&lt;0.05) between groups was found. Table 1. Baseline characteristics of the patients with RA (n=450), mean±SD/n(%) n Adherence mean ADAbs (+) 3 (9.09%) 60.95% p&lt;0.05 ADAbs (-) 30 (90.91%) 84.23% Total 33 (100%) 82.13% No statistically significant differences (p&gt;0.05) involving MTX adherence and its dose were found. Conclusion: While the sample is small, this study suggests that ADAbs development may be influenced by MTX adherence, thereby promoting adequate MTX adherence should be a priority in the daily practice of every rheumatologist. References: [1]World Health Organization. Adherence to long term therapies: evidence for action. 2003. [2]Krieckaert CL, Nurmohamed MT, Wolbink GJ. Methotrexate reduces immunogenicity in adalimumab treated rheumatoid arthritis patients in a dose dependent manner. Annals of the Rheumatic Diseases. 2012;71:1914-1915. [3]Zhang J, Xie F, Delzell E, et al. Impact of biologic agents with and without concomitant methotrexate and at reduced doses in older rheumatoid arthritis patients. Arthritis Care Res (Hoboken). 2015;67(5):624–632. doi:10.1002/acr.22510 [4]Jani M, Barton A, Warren RB, Griffiths CE, Chinoy H. The role of DMARDs in reducing the immunogenicity of TNF inhibitors in chronic inflammatory diseases. Rheumatology (Oxford). 2014;53(2):213–222. doi:10.1093/rheumatology/ket260. Disclosure of Interests: Paula García: None declared, Marta González Fernández: None declared, Mayra Nathali Rivas: None declared, Javier Duruelo: None declared, Elena Garmendia: None declared, Javier Arostegui Lavilla: None declared, Fernando Perez-Ruiz Consultant of: Amgen Lilly, Speakers bureau: Amgen, Alberto Alonso: None declared, Consuelo Modesto: None declared, Boris Anthony Blanco Cáceres: None declared
SAT0495 LONG TERM OUTCOME OF JUVENILE IDIOPATHIC ARTHRITIS IN ADULTHOOD; THE MONOCENTRIC EXPERIENCE OF 520 PATIENTS FOLLOWED FOR 20 YEARS IN A TRANSITION TERTIARY CLINIC OF PEDIATRIC RHEUMATOLOGY.
Authors: I. Pontikaki, S. Carbogno, F. Corona, A. Petaccia, R. Cimaz
Journal: Annals of the Rheumatic Diseases (2020)

Background: Juvenile Idiopathic Arthritis (JIA) is a chronic pediatric inflammatory disease that shows many differences compared to adult-onset arthritis. The different clinical manifestations, the assessment and the management of JIA is the reason that the transition from childhood to adulthood is an important multidimensional process that emphasizes a lot of aspects. Objectives: To describe the long-term outcome of JIA. Methods: Five-hundred and twenty patients affected by JIA and referred to a transition care rheumatology tertiary centre were considered between 1999 and 2019. The outcome assessment included remission, disease duration, medications, number of prosthesis implantation, pregnancies, mortality and social integration (employment status and educational level). Results: A hundred and thirty-eight (26%) males and 382 (73%) females were included; 157 (30%) patients were lost to follow up. The mean age of the patients was 27 (18-57) years, with a mean age at onset of 8 years and an average disease duration of 19 years. Subtypes of JIA at disease onset included 252 (48%) oligoarthritis, 134 (26%) polyarthritis, 64 (12%) systemic arthritis, 22 (4%) psoriatic arthritis, 43 (8%) enthesitis related arthritis and 1 (0.1%) undifferentiated arthritis. Ninty-three (18%) patients suffered of uveitis. Ninty-five implant prosthesis and 16 arthrodesis were recorded. At follow up 198 (38%) patients were on remission of which 107 (20%) off medication. Among the 322 patients still on medication, 84 (16%) were under treatment with oral steroids, 226 (43%) with sDMARDs and 249 (40%) with bDMARDs. Five deaths (1%) occurred in this cohort. Two hundred and thirty-five subjects had a higher educational level, 327 had an employment. We have data of twenty-nine pregnancies. The transition age was considered after the age of 16 years old. The key word for the management of this cohort was the multidisciplinary approach towards each patient, with the collaboration of other specialists (ophthalmologist, orthopedic, dermatologist, gastroenterologist, obstetric and psychologist). Conclusion: In the era of biologic therapy the long-term outcome of JIA underwent an outstanding improvement regarding a lot of variables. Two hundred and thirty-two patients were still followed, not only because of the continuation of the biological therapy, but also for a multidisciplinary care even during remission. JIA often persists over the adulthood, therefore the long term follow-up and care of these patients needs to be conducted by a rheumatologist expertized in JIA in collaboration with other specialists. Disclosure of Interests: None declared
Increased expression of ACE2, the SARS-CoV-2 entry receptor, in alveolar and bronchial epithelium of smokers and COPD subjects
Authors: Merel Jacobs, Hannelore P. Van Eeckhoutte, Sara R.A. Wijnant, Wim Janssens, Guy F. Joos, Guy G. Brusselle, Ken R. Bracke
Journal: European Respiratory Journal (2020)

<b>This study demonstrates increased protein levels of ACE2 in alveolar and bronchial epithelium of smokers and subjects with COPD, which might facilitate host cell entry of SARS-CoV-2</b>https://bit.ly/2ZazOrd
A Boosted Ensemble Algorithm for Determination of Plaque Stability in High-Risk Patients on Coronary CTA
Authors: Subhi J. Al’Aref, Gurpreet Singh, Jeong W. Choi, Zhuoran Xu, Gabriel Maliakal, Alexander R. van Rosendael, Benjamin C. Lee, Zahra Fatima, Daniele Andreini, Jeroen J. Bax, Filippo Cademartiri, Kavitha Chinnaiyan, Benjamin J.W. Chow, Edoardo Conte, Ricardo C. Cury, Gudruf Feuchtner, Martin Hadamitzky, Yong-Jin Kim, Sang-Eun Lee, Jonathon A. Leipsic, Erica Maffei, Hugo Marques, Fabian Plank, Gianluca Pontone, Gilbert L. Raff, Todd C. Villines, Harald G. Weirich, Iksung Cho, Ibrahim Danad, Donghee Han, Ran Heo, Ji Hyun Lee, Asim Rizvi, Wijnand J. Stuijfzand, Heidi Gransar, Yao Lu, Ji Min Sung, Hyung-Bok Park, Daniel S. Berman, Matthew J. Budoff, Habib Samady, Peter H. Stone, Renu Virmani, Jagat Narula, Hyuk-Jae Chang, Fay Y. Lin, Lohendran Baskaran, Leslee J. Shaw, James K. Min
Journal: JACC. Cardiovascular imaging (2020)
Progresses Toward Precision Medicine in<i>RET</i>-altered Solid Tumors
Authors: Carmen Belli, Santosh Anand, Justin F. Gainor, Frederique Penault-Llorca, Vivek Subbiah, Alexander Drilon, Fabrice Andrè, Giuseppe Curigliano
Journal: Clinical Cancer Research (2020)

RET (rearranged during transfection) gene encodes a receptor tyrosine kinase essential for many physiologic functions, but RET aberrations are involved in many pathologies. While RET loss-of-function mutations are associated with congenital disorders like Hirschsprung disease and CAKUT, RET gain-of-function mutations and rearrangements are critical drivers of tumor growth and proliferation in many different cancers. RET-altered (RET+ ) tumors have been hitherto targeted with multikinase inhibitors (MKI) having anti-RET activities, but they inhibit other kinase targets more potently and show limited clinical activities. The lack of target specificity and consequently increased side effects, responsible for dose reduction and drug discontinuation, are critical limitations of MKIs in the clinics. New selective RET inhibitors, selpercatinib and pralsetinib, are showing promising activities, improved response rates, and more favorable toxicity profiles in early clinical trials. This review critically discusses the oncogenic activation of RET and its role in different kinds of tumors, clinical features of RET+ tumors, clinically actionable genetic RET alterations and their diagnosis, and the available data and results of nonselective and selective targeting of RET.
The Lumleian Lectures ON CEREBRO-SPINAL FEVER: Delivered before the Royal College of Physicians of London
Authors: H. Rolleston
Journal: BMJ (1919)

an active growtlh in the pure form.As the subsequient procedure was the same for botlh, details will be given for ane experimICent alone.Experinment. 1.The subculture of Staphylococcus autreus was taken at the end of twenty-four hours' incubation, a good growth being present.* 2. A bacterial emulsion was made by rubbing down the organisms (adhering to the end of a platinum loop which had been iuitro(luced into one.of the larger colonies) in 1.5 c.cm. sterile saliiie solution contained in a sterile test tube.The turbidity of this emulsion was barely visible to the naked eye, and it was calculated that the micro-organisms were present in conisiderable dilution.3. Three sterile test tubes were taken, and inito each was placed 0.5 c.cm. methylene blue, obtained from the stock solution in daily use in the wards.4. To each tube containing the drug 0.03 c.cm. of the bacteiial emulsion was added, the resultant mixture being well shaken to bring, the organisms into intimate association with the methylene blue.5. At the end of half an hour, six hours, and twenity-four lhours respectively, these solutions (which ha(l been shaken frequently) were taken, and agar slopes inoculated by making successive strokes with a platinum loop which had been intro- duced into the emulsion-methylene blue mixture.6.The agar slopes were examined at the end of twenty-four hours, and forty-eight hours.1,e,Suilts.-The half-hoar and six-hour exposures on agar yielded practically the same result, namely, a diffuse growth of Shtphlylo)coccus aureus at the end of twenty-four hours' incuba- tioIn.Tie twenty-four hour exposure showed no growtl visible to ttie naked eye at the end of twenty-four hours' incubation.At the enid of forty-eight hours' incubation, however, a few well dleveloped colonies of Staph y1ococcus autreus were easily seen by the naked eye.The experiments were repeated several times, and gave the same results.
Making junior cricket safer for Sri Lanka (PhD Academy Award)
Authors: Prasanna J Gamage
Journal: British Journal of Sports Medicine (2020)

My aim was to identify areas where cricket could be made safer for junior players in Sri Lanka. For this, I studied the types of musculoskeletal injuries that occur and what injury risks players perceive there to be. Because of its geographical location in south Asia, Sri Lanka has a hot and humid climate. Therefore, I also explored the potential for exertional heat illness (EHI) in this population. Conducting research in Sri Lanka, with limited resources and infrastructure was a challenging task but the potential to make an impact on the safety of so many junior players made this a particularly valuable research experience.

Cricket is immensely popular in Sri Lanka, enjoyed competitively and socially by a large number of participants. To date, no studies have examined safety in junior cricketers in Sri Lanka. As such, there is huge potential for injury prevention measures to make a substantial impact on player safety. I undertook my research in order to provide reliable information to Sri Lankan …
Ethical challenges for pediatric liver organoid transplantation
Authors: Sarah A. Schneemann, Sarah N. Boers, Johannes J. M. van Delden, Edward E. S. Nieuwenhuis, Sabine A. Fuchs, Annelien L. Bredenoord
Journal: Science Translational Medicine (2020)

The authors discuss whether it is ethically acceptable to include children in a first-in-human clinical trial of liver organoid transplantation.
Blood-Pool SPECT/CT in Chronic Ankle Tendinopathy
Authors: Cécile Cuvilliers, Nicolas Icard, Pierre Meneret, Xavier Palard-Novello, Antoine Girard
Journal: Clinical Nuclear Medicine (2020)

Abstract We report 2 cases where blood-pool SPECT/CT had a high added value compared with standard 3-phase bone scintigraphy with only delayed SPECT/CT for the etiological diagnosis of painful ankles. Two men, aged 48 and 62 years, were referred for suspicions of medial and lateral malleoli stress fractures, respectively. Although standard planar blood-pool imaging and delayed SPECT/CT were inconclusive, blood-pool SPECT/CT showed markedly increased uptake along posterior tibial tendon and peroneal tendon, respectively, leading to diagnose tendonitises. These cases illustrate that blood-pool SPECT/CT can extend the diagnostic yield of bone scintigraphy to extraosseous origin, particularly in chronic lower extremities pain.
The Role of Topical Antibiotic Prophylaxis in Oculofacial Plastic Surgery
Authors: Davin C. Ashraf, Oluwatobi O. Idowu, Qinyun Wang, Tak YeEun, Thomas S. Copperman, Sombat Tanaboonyawat, Benjamin F. Arnold, Catherine E. Oldenburg, M. Reza Vagefi, Robert C. Kersten
Journal: Ophthalmology (2020)
FRI0325 UVEITIS OCCURRENCE IN EARLY INFLAMMATORY BACK PAIN. FIVE YEARS DATA FROM A PROSPECTIVE FRENCH NATIONWIDE COHORT
Authors: D. Wendling, C. Prati, T. Lequerre, C. Miceli Richard, M. Dougados, A. Moltó, X. Guillot
Journal: Annals of the Rheumatic Diseases (2020)

Background: Uveitis is the most frequent extra rheumatological manifestation in axial Spondyloarthritis (SpA). DESIR is a prospective multicenter cohort of patients with early inflammatory back pain suggestive of SpA. We reported previously a 8.5% baseline prevalence of uveitis for the patients included in the cohort; this history of uveitis at the first visit of the cohort was associated with inflammatory bowel disease (IBD) and preceding infection (1). Objectives: The aim of the study was to evaluate the prevalence and incidence of uveitis over the first five years of prospective follow-up of the cohort, and to evaluate its associated factors. Methods: DESIR is a prospective observational cohort of patients with recent onset inflammatory back pain (more than 3 months, less than 3 years), suggestive of axial SpA, All available factors in the database were compared between patients with and without uveitis at 5 years, by uni and then multivariate analysis. Baseline factors associated with new cases of uveitis occurrence over the 5 years were also analyzed. Significance: p less than 0.05. Results: After 5 years, 91 patients (out of 480 with complete follow-up) had at least one uveitis episode, giving an estimated prevalence of 18.9% [95%CI: 15.4-22.4]. In multivariate analysis, uveitis was associated with dactylitis (OR 2.92 [2.06 – 4.14]; p=0.002**), ESR &gt; 7mm (median value) (OR 2.19 [1.57 – 3.06]; p=0.018*). New incident uveitis occurred in 31 cases over 5 years, giving an estimated incidence rate of 1.29 [0.84 – 1.74] / 100 patient-years. New incidence of uveitis was associated in multivariate analysis with the following baseline factors: diagnosis of SpA (OR 9.65 [3.21 – 28.96]; p=0.039*), total sacro iliac MRI inflammatory SPARCC score (central reading) over median (OR 3.98 [2.26 – 7]; p=0.015*), dactylitis (OR 4.7 [2.65 – 8.36]; p=0.007**), syndesmophyte score over median (central reading) (OR 0.22 [0.1 – 0.45]; p=0.039*). No significant association was found with HLA-B27, cs or b DMARDs, BASDAI, ASDAS, BASFI. Conclusion: Five-years data of the DESIR cohort allowed an estimation of incidence rate of uveitis of 1.3/100p-y; over five years, uveitis was associated with dactylitis, biologic and sacro iliac MRI inflammation. References: [1]Wendling D, et al.Arthritis Care Res(Hoboken). 2012 Jul;64(7):1089-93. Disclosure of Interests: Daniel Wendling: None declared, Clément Prati: None declared, Thierry Lequerre: None declared, Corinne Miceli Richard: None declared, Maxime Dougados Grant/research support from: AbbVie, Eli Lilly, Merck, Novartis, Pfizer and UCB Pharma, Consultant of: AbbVie, Eli Lilly, Merck, Novartis, Pfizer and UCB Pharma, Speakers bureau: AbbVie, Eli Lilly, Merck, Novartis, Pfizer and UCB Pharma, Anna Moltó Grant/research support from: Pfizer, UCB, Consultant of: Abbvie, BMS, MSD, Novartis, Pfizer, UCB, xavier guillot: None declared
Etiologic Index — A Case-Only Measure of <i>BRCA1/2</i>–Associated Cancer Risk
Authors: Raymond Hughley, Rosa Karlic, Himanshu Joshi, Clare Turnbull, William D Foulkes, Paz Polak
Journal: New England Journal of Medicine (2020)

Etiologic Index of BRCA1 and BRCA2 A proposed etiologic index, based on genomic variation in tumor cells and matched normal cells, suggests the possibility of involvement of variant BRCA1 and BRCA2...
2型糖尿病の症状,重度低血糖,および死亡率における相関性:ACCORD試験のレトロスペクティブ疫学分析
Authors: Bonds Denise E, Miller Michael E, Bergenstal Richard M, Buse John B, Byington Robert P, Cutler Jeff A, Dudl R James, Ismail-Beigi Faramarz, Kimel Angela R, Hoogwerf Byron, Horowitz Karen R, Savage Peter J, Seaquist Elizabeth R, Simmons Debra L, Sivitz William I, Speril-Hillen Joann M, Sweeney Mary Ellen
Journal: BMJ (2010)
Predicted declines in population hold major global challenges
Authors: Shaun Griffin
Journal: BMJ (2020)

Researchers have forecast that the global population will peak at 9.73 billion in 2064 and decline to 8.79 billion in 2120—a level significantly lower than previous estimates.1

Over this period the number of people over 80 will increase by over 600%, from 141 to 866 million, while the number of children under five years will decline by 41% from 681 million to 401 million. 

The main determinant of the decreased 2120 population size is reducing total fertility rate, which is largely influenced by increasing educational attainment among women and access to contraception, the researchers said in the Lancet .1

In the context of a declining population “some countries will sustain their populations through …
A Swedish primary healthcare prevention programme focusing on promotion of physical activity and a healthy lifestyle reduced cardiovascular events and mortality: 22-year follow-up of 5761 study participants and a reference group
Authors: Gunilla Journath, Niklas Hammar, Max Vikström, Anette Linnersjö, Göran Walldius, Ingvar Krakau, Peter Lindgren, Ulf de Faire, Mai-Lis Hellenius
Journal: British Journal of Sports Medicine (2020)

Objective To evaluate long-term risk of first cardiovascular (CV) events, CV deaths and all-cause deaths in community-dwelling participants of a cardiovascular disease (CVD) prevention programme delivered in a primary care setting. Methods Individuals who visited a primary healthcare service in Sollentuna (Sweden) and agreed to participate in the programme between 1988 and 1993 were followed. They had at least one CV risk factor but no prior myocardial infarction and received support to increase physical activity using the programme Physical Activity on Prescription and to adopt health-promoting behaviours including cooking classes, weight reduction, smoking cessation and stress management. Participants (n=5761) were compared with a randomly selected, propensity score-matched reference group from the general population in Stockholm County (n=34 556). All individuals were followed in Swedish registers until December 2011. Results In the intervention group and the reference group there were 698 (12.1%) and 4647 (13.4%) first CV events, 308 (5.3%) and 2261 (6.5%) CV deaths, and 919 (16.5%) and 6405 (18.5%) all-cause deaths, respectively, during a mean follow-up of 22 years. The HR (95% CI) in the intervention group compared with the reference group was 0.88 (0.81 to 0.95) for first CV events, 0.79 (0.70 to 0.89) for CV deaths and 0.83 (0.78 to 0.89) for all-cause deaths. Conclusions Participation in a CVD prevention programme in primary healthcare focusing on promotion of physical activity and healthy lifestyle was associated with lower risk of CV events (12%), CV deaths (21%) and all-cause deaths (17%) after two decades. Promoting physical activity and healthy living in the primary healthcare setting may prevent CVD.
A Genetic Vaccine Encoding Shared Cancer Neoantigens to Treat Tumors with Microsatellite Instability
Authors: Guido Leoni, Anna Morena D'Alise, Gabriella Cotugno, Francesca Langone, Irene Garzia, Maria De Lucia, Imma Fichera, Rosa Vitale, Veronica Bignone, Fabio Giovanni Tucci, Federica Mori, Adriano Leuzzi, Elena Di Matteo, Fulvia Troise, Adele Abbate, Rossella Merone, Valentino Ruzza, Maria Grazia Diodoro, Mahesh Yadav, Monica Gordon-Alonso, Cristophe Vanhaver, Maddalena Panigada, Elisa Soprana, Antonio Siccardi, Antonella Folgori, Stefano Colloca, Pierre van der Bruggen, Alfredo Nicosia, Armin Lahm, Maria Teresa Catanese, Elisa Scarselli
Journal: Cancer Research (2020)

Abstract Tumors with microsatellite instability (MSI) are caused by a defective DNA mismatch repair system that leads to the accumulation of mutations within microsatellite regions. Indels in microsatellites of coding genes can result in the synthesis of frameshift peptides (FSP). FSPs are tumor-specific neoantigens shared across patients with MSI. In this study, we developed a neoantigen-based vaccine for the treatment of MSI tumors. Genetic sequences from 320 MSI tumor biopsies and matched healthy tissues in The Cancer Genome Atlas database were analyzed to select shared FSPs. Two hundred nine FSPs were selected and cloned into nonhuman Great Ape Adenoviral and Modified Vaccinia Ankara vectors to generate a viral-vectored vaccine, referred to as Nous-209. Sequencing tumor biopsies of 20 independent patients with MSI colorectal cancer revealed that a median number of 31 FSPs out of the 209 encoded by the vaccine was detected both in DNA and mRNA extracted from each tumor biopsy. A relevant number of peptides encoded by the vaccine were predicted to bind patient HLA haplotypes. Vaccine immunogenicity was demonstrated in mice with potent and broad induction of FSP-specific CD8 and CD4 T-cell responses. Moreover, a vaccine-encoded FSP was processed in vitro by human antigen-presenting cells and was subsequently able to activate human CD8 T cells. Nous-209 is an “off-the-shelf” cancer vaccine encoding many neoantigens shared across sporadic and hereditary MSI tumors. These results indicate that Nous-209 can induce the optimal breadth of immune responses that might achieve clinical benefit to treat and prevent MSI tumors. Significance: These findings demonstrate the feasibility of an “off-the-shelf” vaccine for treatment and prevention of tumors harboring frameshift mutations and neoantigenic peptides as a result of microsatellite instability.