tbuckley/cabot-search huggingface dataset:
AB0321 MORTALITY AND COMPLICATION OF PATIENTS WITH RHEUMATOID ARTHRITIS ADMITTED TO INTENSIVE CARE UNIT IN KYUSHU UNIVERSITY HOSPITAL
Authors: Toshifumi Fujiwara, Yukio Akasaki, Satoshi Ikemura, Jun-Ichi Fukushi, Yasuharu Nakashima
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> The patients with rheumatoid arthritis (RA) are associated with high mortality caused by comorbidity and complication, and are often required the intensive treatment. Severe infections are among the most common causes of their mortality in intensive care unit (ICU)<sup>1)2)</sup>. <h3>Objectives</h3> To determine prognostic factors and mortality in patients with RA, including juvenile idiopathic arthritis (JIA), admitted to the ICU in Kyushu University Hospital, we examined the treatments of RA and JIA, comorbidities, complications, the reasons admitted to the ICU, intensive treatments, mortalities within 30 days, 90 days, and a year. <h3>Methods</h3> Between January 2008 and March 2018, 70 patients (20 males, 50 females) with RA (68) or JIA (2) staying at the ICU of our institution for 48 hours and over were included in this study. The admission to the ICU were performed total 77 of times because 5 patients were readmitted. The average of age and RA duration at the admission was 65.817.7 years (5-96) and 13.514.8 years (0-61), respectively, and the average of follow-up duration was 879.9992.0 days (3-3988). <h3>Results</h3> The mortality within 30 and 90 days were 21.4% (15/70) and 27.1% (19/70), respectively, and 24 of 65 patients (36.9%), excluded 5 patients due to the change of hospital, were dead within a year. The reasons for ICU admission included cardiovascular complications (22.9%), infection (30.0%), neurological complications (7.1%), respiratory problem (15.7%), gastrointestinal problems (4.3%), endocrinological cause (2.9%), liver problems (7.1%), kidney problems (4.3%), and others (5.7%). The average of ICU length of stay was 7.27.6 days (2-39). The group of 30 days mortality was significantly higher in the amount of prednisone (8.15.8 vs 4.54.9), Charlson Comorbidity Index3) (5.12.5 vs 2.71.4), and APACHEII4) (21.79.2 vs 14.55.5) scores. The fatal outcomes within 30 days was mainly caused by infection (46.7%). In blood data, the low levels of platelet number, total protein, and albumin, and the high levels of creatinine and prothrombin time international normalize ratio at the time of admission of ICU were significantly poorer prognoses. <h3>Conclusion</h3> Our study has shown the high mortality of RA patients admitted to the ICU, and some blood data could be predicted poor prognosis. <h3>References</h3> [1] Moreels M, et al.: Intensive Care Med 2005 [2] Brunnler T, et al.: Intern Med 2015 [3] Quan H, et al.: Am J Epidemiol 2011 [4] Knaus WA, et al.: Crit Care Med 1985 <h3>Disclosure of Interests</h3>
FRI0586 THE EFFECT OF TOCILIZUMAB IN THE PREVENTION OF FAMILIAL MEDITERRANEAN FEVER ATTACKS
Authors: Seda Colak, Emre Tekgoz, Muhammet Çınar, Sedat Yilmaz
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Familial Mediterranean Fever (FMF) is the most frequent hereditary autoinflammatory disease in the worldwide. Colchicine is the mainstay of the treatment that is used for both preventing the attacks and developing amyloidosis. In case of colchicine resistance, which constitutes almost 5% of all patients, there are some alternatives such as anti-TNF agents, IL-6 and IL-1 antagonists. These agents have also been used in patients with established amyloidosis secondary to FMF. Tocilizumab (TCZ), an IL-6 receptor antagonist, although is effective in the treatment of amyloidosis, little known about its effectiveness in the preventing of febrile attacks. <h3>Objectives</h3> In this study, we aimed to find out whether TCZ therapy decrease the frequency of recurrent attacks of FMF or not. <h3>Methods</h3> This retrospective cross-sectional study designed in a tertiary rheumatology clinic between the years 2009 and 2019. A total of 15 patients were given intravenous TCZ at a dose of 8mg/kg/month, to improve amyloidosis associated with FMF. Data of demographic and clinical characteristics of patients were obtained retrospectively from patient files. <h3>Results</h3> Three female and 12 male patients received TCZ for amyloidosis treatment. The mean age of patients was 42.07±14.37 years and disease duration was 25.73±10.86 years. All of the patients had biopsy results providing amyloidosis. According to international severity scoring system for FMF, all of the patients had severe disease. Demographic and clinical data were shown in Table 1. The frequency of attacks was evaluated during TCZ treatment, and it was reported that 1 patient had no response, 6 patients had decreased attack frequency and 8 patients had no attacks. Serious adverse events were seen in none of the patients. MEFV:Mediterranean Fever, TCZ:Tocilizumab <h3>Conclusion</h3> Tocilizumab is found to be effective on improvement of amyloidosis. In the current analysis, we found that TCZ also decreases the frequency of recurrent attacks in patients with FMF. Besides, TCZ is well tolerated among the patients. Further and prospective studies with larger sample are needed to support these results. <h3>References</h3> [1] Yilmaz S, Cinar M, Simsek I, Erdem H, Pay S. Tocilizumab in the treatment of patients with AA amyloidosis secondary to familial Mediterranean fever. Rheumatology2015;54:564-565 <h3>Disclosure of Interests</h3> None declared
THU0302 OUTCOMES OF PREGNANCY IN BEHCET’S DISEASE
Authors: Zemfira Alekberova, Regina Goloeva, Alexander Lila
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Behcet's disease (BD) is multisystemic disease of unknown cause. The relationship between BD and pregnancy is reported in limited number of studies. <h3>Objectives:</h3> To evaluate outcomes of pregnancies in BD patients (pts). <h3>Methods:</h3> We retrospectively collected data of 22 women with BD diagnosis (according to ISGBD 1990 and ICBD 2014) and their 68 pregnancies. Pts' mean age was 30 [26;35] yrs, disease duration 7 [2;10] yrs. Ten (45,5%) pts had severe BD according to Ch.Zouboulis classification (due to generalized uveitis, retinal vasculitis and parenchymatous CNS lesions), while other 10 (45,5%) pts had mild disease with mainly dermal-mucous manifestations, and remaining two (9%) pts had moderate disease. These patients did not receive cytotoxic therapy. <h3>Results:</h3> Sixty-eight pregnancies in 22 pts resulted in 45 live birth (4 cesarean section in 2 pts). Four patients had 11 medical abortions on request before 12 weeks of gestation, one patient - due to medical reasons (rubella on the 7<sup>th</sup> week of gestation). Seven (32%) out of 22 pts had adverse pregnancy outcomes. Five (23%) pts had 8 intrauterine deaths: one patient – 3 intrauterine deaths (4-10 weeks), two pts – 2 (10-12 weeks) and one -1 intrauterine deaths (10 weeks). Two (9%) pts had 3 miscarriages 5–10 weeks. Antiphospholipid syndrome was never detected in pts from this cohort. BD Severity and pathology of pregnancy Out of 45 babies children born by BD patients only two had relapsing aphthous stomatitis and one – congenital glaucoma ("Neurobehcet" inherited from mother). <h3>Conclusion:</h3> BD pts demonstrated high rates of adverse pregnancy outcomes. Unfavorable outcomes of pregnancy were documented in pts regardless (with all grades of) BD severity. <h3>Reference:</h3> [1] Zouboulis C., Vaiopoulos G., Macromichelakis N. et al. Onset signs, clinical course, prognosis, treatment and outcome of adult patients with Adamantiades – Behcet's disease in Greece. Clin.Exp.Rheum.2003, 21, (suppl.30) S19-S26. <h3>Disclosure of Interests:</h3> None declared
Cerebral organoids at the air–liquid interface generate diverse nerve tracts with functional output
Authors: Stefano L. Giandomenico, Susanna B. Mierau, George M. Gibbons, Lea M. D. Wenger, Laura Masullo, Timothy Sit, Magdalena Sutcliffe, Jerome Boulanger, Marco Tripodi, Emmanuel Derivery, Ole Paulsen, András Lakatos, Madeline A. Lancaster
Journal: Nature Neuroscience (2019)
Genomic Characterization of Six Virus-Associated Cancers Identifies Changes in the Tumor Immune Microenvironment and Altered Genetic Programs
Authors: Frederick S. Varn, Evelien Schaafsma, Yue Wang, Chao Cheng
Journal: Cancer Research (2018)

Abstract Viruses affect approximately 20% of all human cancers and induce expression of immunogenic viral oncoproteins that make these tumors potent targets for immune checkpoint inhibitors. In this study, we apply computational tools to The Cancer Genome Atlas (TCGA) and other genomic datasets to define how virus infection shapes the tumor immune microenvironment and genetic architecture of 6 virus-associated tumor types. Across cancers, the cellular composition of the microenvironment varied by viral status, with virus-positive tumors often exhibiting increased infiltration of cytolytic cell types compared with their virus-negative counterparts. Analyses of the infiltrating T-cell receptor repertoire in these patients revealed that Epstein–Barr virus infection was associated with decreased receptor diversity in multiple cancers, suggesting an antigen-driven clonal T-cell response. Tissue-specific gene-expression signatures capturing virus-associated transcriptomic changes successfully predicted virus status in independent datasets and were associated with both immune- and proliferation-related features that were predictive of patient prognosis. Together, the analyses presented suggest viruses have distinct effects in different tumors, with implications for immunotherapy. Significance: This study utilizes TCGA and other genomic datasets to further our understanding of how viruses affect the tumor immune response in different cancer types. Graphical Abstract: http://cancerres.aacrjournals.org/content/canres/78/22/6413/F1.large.jpg. Cancer Res; 78(22); 6413–23. ©2018 AACR.
PD-L1 expression on nonclassical monocytes reveals their origin and immunoregulatory function
Authors: Mariaelvy Bianchini, Johan Duchêne, Donato Santovito, Maximilian J. Schloss, Maximilien Evrard, Holger Winkels, Maria Aslani, Sarajo K. Mohanta, Michael Horckmans, Xavier Blanchet, Michael Lacy, Philipp von Hundelshausen, Dorothee Atzler, Andreas Habenicht, Norbert Gerdes, Jaroslav Pelisek, Lai Guan Ng, Sabine Steffens, Christian Weber, Remco T. A. Megens
Journal: Science Immunology (2019)

PD-L1 + Ly6C lo monocytes derive from Ly6C hi monocytes in bone marrow and control T cell survival in tertiary lymphoid organs.
Abstract 20174: Impact of Entrance Examination on Development of Nonalcoholic Fatty Liver Disease in New University Students
Authors: Tetsuo Konno, Michiko Ikeda, Miho Shimizu, Tsuyoshi Yoshimuta, Hiroaki Yoshikawa, Junji Koizumi, Tohihide Okada, Ayako Suzuki, Masakazu Yamagishi
Journal: Circulation (2015)

Introduction: Nonalcoholic fatty liver disease (NAFLD) has emerged as a risk factor for cardiovascular diseases. In Japan, most of high-school graduates who fail to pass the university entrance examinations attend full-time cram schools to devote themselves to preparing for the examinations for another year(s). These full-time cram-school students, called as “Ronin samurais” in Japanese, could be at risk for development of NAFLD because they live sedentary lifestyle under persistent academic stress. Hypothesis: We assessed the hypothesis that the Ronin-samurai period before entering university is associated with NAFLD in new university students. Methods: This cross-sectional study included 1777 new university students who underwent a group medical check-up immediately after admission into Kanazawa University. Results: Of the 1777 students, 319 (18%) went through the Ronin-samurai period before entering university (Ronin-samurai group). The Ronin-samurai group showed significantly higher body mas index, total cholesterol levels, and alanine aminotransferase (ALT) values compared to the non-Ronin group (n = 1458). The estimated mean difference (B) in ALT values between the two groups was 5.6 ± 1.2 IU/L (P &lt;0.0001). The association persisted even after adjusting for age, gender and metabolic risk factors (B = 3.7 ± 1.5, P = 0.014). The follow-up analysis in 94 students with elevated ALT values (≥ 40 IU/L) after medical check-up showed a drastic decrease in mean ALT values in both groups only 9 weeks after entering the university (Figure), although no lifestyle intervention was performed during the time period. Conclusions: Spending an extra year(s) preparing for the entrance examination, as Ronin samurais, could contribute to this previously unrecognized “entrance examination-related NAFLD” in new university students.
SAT0304 RELATIONSHIP BETWEEN INTERLEUKIN-23 AND GASTROINTESTINAL INVOLVEMENT IN PATIENTS WITH SYSTEMIC SCLEROSIS
Authors: Ana Zekovic, Misa Vreca, Vesna Spasovski, Vesna Skodric-Trifunovic, Ljiljana Markovic-Denic, Marina Andjelkovic, Sonja Pavlovic, Nemanja Damjanov, Nemanja Damjanov
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Growing evidence suggests that T-cell proliferation and cytokine secretion play an important role in the pathogenesis of systemic sclerosis (SSc). Gut involvement is the leading cause of morbidity in patients with SSc. In this study we evaluated interleukin-23 (IL-23) protein expression profiles and investigated its association with gastrointestinal involvement in SSc patients. <h3>Objectives</h3> To evaluate IL-23 expression profiles and to explore association between IL-23 and gastrointestinal involvement in SSc patients. <h3>Methods</h3> Study included 31 SSc patients. The expression level of IL-23 mRNA was determined by qRT-PCR method and Enzyme-Linked Immunosorbent Assay (ELISA) was used for analysis of IL-23 serum protein level. We used UCLA GIT 2.0 questionnaire to assess gastrointestinal (GIT) involvement in SSc patients. <h3>Results</h3> We found a positive correlation between disease duration and expression levels of IL-23mRNA (r = 0.49, p&lt;0.05). Nine SSc patients with high IL-23 levels (cut off point 6.8 pg/ml) had significantly higher UCLA GIT 2.0 score, compared to 22 SSc patients with normal IL-23 levels (p&lt;0.05). Serum level of IL-23 positively correlated with total GIT score (r = 0.35, p&lt;0.05) and distension scale score (r= 0.5, p&lt;0.05). <h3>Conclusion</h3> High IL-23 serum levels significantly correlated with gastrointestinal involvement (higher UCLA GIT 2.0 score) in patients with SSc. <h3>References</h3> [1] Komura K, Fujimoto M, Hasegawa M, Hara T, Muroi E, et al. (2008) Increased serum interleukin 23 in patients with systemic sclerosis. J Rheumatol: 35; 120. [2] Savarino E, Furnari M, De Bortoli N, Martinucci I, Bodini G, Ghio M, et al. (2014). Gastrointestinal involvement in systemic sclerosis. Presse Med43:e279-91. [3] Khanna D, Hays RD, Maranian P, Seibold JR, Impens A, Mayes MD, et al. (2009) Reliability and validity of the University of California, Los Angeles scleroderma clinical trial consortium gastrointestinal tract instrument. Arthritis Rheum; 61: 1257-63. [4] Zekovic A, Damjanov N (2017) Validation of Serbian version of UCLA Scleroderma Clinical Trial Consortium Gastrointestinal Tract Instrument in 104 patients with systemic sclerosis. Rheumatol Int;37(5):735-741. <h3>Disclosure of Interests</h3> Ana Zekovic: None declared, Misa Vreca: None declared, Vesna Spasovski: None declared, Vesna Skodric-Trifunovic: None declared, Ljiljana Markovic-Denic: None declared, Marina Andjelkovic: None declared, Sonja Pavlovic: None declared, Nemanja Damjanov Grant/research support from: AbbVie, Pfizer and Roche, Consultant for: Abbvie, Gedeon Richter, Merck, Novartis, Pfizer and Roche., Speakers bureau: Abbvie, Gedeon Richter, Merck, Novartis, Pfizer and Roche.
Fecal Microbiota Transplantation for Ulcerative Colitis—Reply
Authors: Samuel P. Costello, Michael A. Conlon, Jane M. Andrews
Journal: JAMA (2019)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Sequential Therapy with PARP and WEE1 Inhibitors Minimizes Toxicity while Maintaining Efficacy
Authors: Yong Fang, Daniel J. McGrail, Chaoyang Sun, Marilyne Labrie, Xiaohua Chen, Dong Zhang, Zhenlin Ju, Christopher P. Vellano, Yiling Lu, Yongsheng Li, Kang Jin Jeong, Zhiyong Ding, Jiyong Liang, Steven W. Wang, Hui Dai, Sanghoon Lee, Nidhi Sahni, Imelda Mercado-Uribe, Tae-beom Kim, Ken Chen, Shiaw-Yih Lin, Guang Peng, Shannon N. Westin, Jinsong Liu, Mark J. O'Connor, Timothy A. Yap, Gordon B. Mills
Journal: Cancer Cell (2019)
Inhibition of EZH2 Ameliorates Lupus‐Like Disease in MRL/<i>lpr</i> Mice
Authors: Dallas M. Rohraff, Ye He, Evan A. Farkash, Mark Schonfeld, Pei‐Suen Tsou, Amr H. Sawalha
Journal: Arthritis & Rheumatology (2019)

Objective We previously identified a role for EZH2, a transcriptional regulator in inducing proinflammatory epigenetic changes in lupus CD4+ T cells. This study was undertaken to investigate whether inhibiting EZH2 ameliorates lupus‐like disease in MRL/ lpr mice. Methods EZH2 expression levels in multiple cell types in lupus patients were evaluated using flow cytometry and messenger RNA expression data. Inhibition of EZH2 in MRL/ lpr mice was achieved by intraperitoneal 3′‐deazaneplanocin (DZNep) administration using a preventative and a therapeutic treatment model. Effects of DZNep on animal survival, anti–double‐stranded DNA (anti‐dsDNA) antibody production, proteinuria, renal histopathology, cytokine production, and T and B cell numbers and percentages were assessed. Results EZH2 expression levels were increased in whole blood, neutrophils, monocytes, B cells, and CD4+ T cells in lupus patients. In MRL/ lpr mice, inhibition of EZH2 by DZNep was confirmed by significant reduction of EZH2 and H3K27me3 in splenocytes. Inhibiting EZH2 with DZNep treatment before or after disease onset improved survival and significantly reduced anti‐dsDNA antibody production. DZNep‐treated mice displayed a significant reduction in renal involvement, splenomegaly, and lymphadenopathy. Lymphoproliferation and numbers of double‐negative T cells were significantly reduced in DZNep‐treated mice. Concentrations of circulating cytokines and chemokines, including tumor necrosis factor, interferon‐γ, CCL2, RANTES/CCL5, interleukin‐10 (IL‐10), keratinocyte‐derived chemokine/CXCL1, IL‐12, IL‐12p40, and CCL4/macrophage inflammatory protein 1β, were decreased in DZNep‐treated mice. Conclusion EZH2 is up‐regulated in multiple cell types in lupus patients. Therapeutic inhibition of EZH2 abrogates lupus‐like disease in MRL/ lpr mice, suggesting that EZH2 inhibitors may be repurposed as a novel therapeutic option for lupus patients.
PB1743 LIPOSOMAL ANNAMYCIN ‐ A NEW GENERATION ANTHRACYCLINE THAT OVERCOMES MDR AND HAS NO CARDIAC TOXICITY FOR THE TREATMENT OF R/R AML
Authors: R. Shepard
Journal: HemaSphere (2019)

Background: Anthracyclines remain the backbone for induction therapy in the treatment of AML. Unfortunately, most patients will relapse with refractory disease and quickly succumb to their AML. One of the major reasons if not the major reason for developing resistance is the development of MDR. Annamycin was developed and has been shown both preclinically and clinically to overcome MDR and have no cardiac toxicity. Furthermore, it is formulated in a nanomolecular bi‐lamellar liposomal delivery mechanism that targets the leukemic cells in the bone marrow and spares cardiac and other normal cells. Therefore, a new phase I/II clinical trial has been started in both the US and Europe using L‐Annamycin for the treatment of all patients with R/R AML agnostic of mutational status. Aims: The aim of the phase I component is to determine the RP2D of L‐Annamycin for the treatment of R/R AML. The phase II component is designed to demonstrate efficacy leading to a phase II registration study for accelerated approval in both the US and EU. PK determinations are being performed for all patients. Methods: The phase I component is a standard modified Fibonacci 3+3 design to determine the RP2D. An additional 21 patients will be enrolled as an early determinant of efficacy at the RP2D. The sample size for this is based upon an expected response rate of 15%. Utilizing the optimized Simon two stage design, the assumption is that alpha = 0.1 and beta = 0.2. If less than 1 CR is observed in the first 14 subjects, the study will be stopped for futility. To be declared a success, at least 4 subjects of the 21 needs to demonstrate a CR. A DMC will monitor all data and decide if the study should continue and if any changes to the protocol are needed. Results: The study is ongoing in both Europe and the US. The first cohort has completed in the US. Even at the very low starting dose, one of the three patients had a near CR with just MRD after just one three‐day course of L‐Annamycin. The first cohort in Europe has enrolled two patients and updated results will be presented at the EHA Congress. Summary/Conclusion: Anthracyclines remain the backbone of induction therapy in AML but most patients will relapse and die from their refractory disease. Resistance develops because of MDR. L‐Annamycin overcomes this and has little to no cardiac toxicity even with up to eight cycles. This study will is designed to demonstrate its efficacy in all patients with R/R AML including the majority with no targetable mutations. image
A Combination of Oxo-M and 4-PPBP as a potential regenerative therapeutics for tendon injury
Authors: Solaiman Tarafder, Christopher Ricupero, Sumeet Minhas, Rebecca J Yu, Ashleigh D Alex, Chang H Lee
Journal: Theranostics (2019)

Tendons injuries frequently result in scar-like tissue with poor biochemical structure and mechanical properties. We have recently reported that CD146