tbuckley/cabot-search huggingface dataset:
Distinct Implications of TP53 Hits for Patients with Treatment-Related MDS and AML
Authors: Teodora Kuzmanovic, Bhumika J. Patel, Yasunobu Nagata, Hassan Awada, Cassandra M. Hirsch, Bartlomiej P. Przychodzen, Srinivasa Reddy Sanikommu, Louis Williams, Sudipto Mukherjee, Anjali S. Advani, Aziz Nazha, Aaron T. Gerds, Tomas Radivoyevitch, Hetty E. Carraway, Mikkael A. Sekeres, Jaroslaw P. Maciejewski
Journal: Blood (2018)
FRI0048 Mortality and morbidity of rheumatoid arthritis-associated lung disease during a 10-year period: a longitudinal cohort study of 103 japanese patients
Authors: S. Shimoyama, Y. Fujieda, M. Kato, K. Oku, T. Bohgaki, O. Amengual, S. Yasuda, T. Atsumi
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Subclinical and overt lung diseases associated with rheumatoid arthritis (RA-LD) are present in 30%–50% of the patients. Early and effective intervention improved joint prognosis in RA. By contrast, lung complications are still the primary contributors to premature deaths in patients with RA. Lung complication in RA can be due to a variety of conditions. However, the individual mortality and progression of pulmonary manifestations have not been established. <h3>Objectives</h3> To clarify the prognostic factors of patients with RA-LD. <h3>Methods</h3> This cohort study comprised RA patients examined with lung high resolution CT (HRCT) scan regardless of respiratory symptoms from 2005 to 2009. Respiratory diagnoses were certified by pulmonologists. The patients were reassessed by one follow-up CT scan after 10 years. All patients were evaluated for the events defined as death, serious infections and others (admission due to bone fracture, and ischaemic heart disease) from 2005 to 2017. Mortality risks were assessed using Kaplan-Meier method. <h3>Results</h3> Clinical features of 103 (82 females) patients are shown in table 1. Thirty-one (30%) had RA-LD including 18 interstitial pneumonia and 13 bronchiolitis at the start of observation. Mean observation period was 110 months. During observation, patients without RA-LD (non RA-LD) never developed new lung complications. The 10 year survival rate (SR) was 92% (mortality rate was 1.3 per 100 patient-years) and the 10 year event free survival rate (EFS) 69% (event rate was 4.8 per 100 patient-years). SR in RA-LD was significantly low compared with non RA-LD (p=0.008) (figure 1). EFS in RA-LD was significantly lower than in non RA-LD (p=0.03). Types of lung complication didn't correlate with high mortality. The causes of death comprised infection (55%), malignant tumour (27%), interstitial pneumonia (9%), and the others (9%). The adverse events included infection (41%), malignant tumour (21%), bone fracture (15%), cardiac disease (10%), and severe drug eruption including Steven-Johnson syndrome (13%). Univariate analysis showed that infection (p&lt;0.001, HR 26.7) and acute exacerbation of RA-LD (p&lt;0.001, HR 57.3, 95% CI 13–287) were strong risk factors for deaths. <h3>Conclusions</h3> RA-LD is a serious complication in RA, and related with a high mortality. <h3>Disclosure of Interest</h3> None declared
THU0226 Serial interferon-gamma release assays in patients with rheumatoid arthritis treated with biologic agents
Authors: Y.J. Huang, Y.F. Fang, Y.F. Chen, P.H. Tsai, C.F. Kuo, K.H. Yu, S.F. Luo
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> It is increasing attention about the risk of latent tuberculosis infection (LTBI) reactivation during the treatment of biologic agents for patients with rheumatoid arthritis. Taiwan rheumatology association recommend performing at least annual interferon-gamma release assays (IGARs) testing during biologic treatment course because of the moderate prevalence of tuberculosis in Taiwan.[<sup>1</sup> Although several studies have reported the risk of active tuberculosis infection in patients with rheumatoid arthritis (RA), the long-term serial IGARs testing in patients with RA is limited. <h3>Objectives</h3> The aims of this study is to use serial interferon-gamma release assays(IGRAs) as a screening tool in patients with rheumatoid arthritis treated with different biologic agents in Taiwan. <h3>Methods</h3> We retrospectively collected 189 patients with rheumatoid arthritis receiving biologic agents between 2013 to 2017 in Chang Gung Memorial hospital in Taiwan. All RA patients underwent semi-annual IGRA test during biologic agents treatment. <h3>Results</h3> The seroconversion rate of IGAR in patients with rheumatoid arthritis after biologic treatment is 6.9%. The median seroconversion period is 19 months. Out of the 13 patients with seroconversion, 8 (61.5%) patients were treated with TNF block and 5 (38.5%) patients were treated with non-TNF blocker. All the patients with seroconversion evaluate the possible active TB infection and 69.2% (9/13) received chemoprophylactic therapy by isoniazid. There is no active tuberculosis infection during serial IGAR tests. The risk factor included high baseline TBAg-nil/nil (OR 3.44, CI 6.64–1.78), leflunomide(OR 11.51, CI 61.34–2.16). <h3>Conclusions</h3> Our study revealed patients with rheumatoid arthritis receiving long-term biologic therapy had a low rate IGAR seroconversion rate (6.9%). Patients with background Leflunomide had higher odds ratio of seroconversion. However, the clinical importance of IGAR serocoversion remain controversial and further long-term large scale investigation is needed. <h3>Reference</h3> [1] Chen Y-H. 2015TRA revised recommendations for screening and management of tuberculosis infection in patients before and after anti-tumor necrosis factor-alpha biological treatment. 2015;29:1–8. <h3>Disclosure of Interest</h3> None declared
Sustained overexpression of FoxM1B which increases liver regenerative capacity may have minimal effects on hepatocellular carcinoma development
Authors: Olga A. Kalinina, Sergey A. Kalinin, Evelyne W. Polack, Igor Mikaelian, Robert H. Costa, Suchismita Panda, Guy R. Adami
Journal: Cancer Research (2004)

5056   FoxM1B is a member of the Forkhead box (Fox) transcription factor family whose members play important roles in regulating embryogenesis, cellular proliferation, cellular differentiation and longevity. Expression of FoxM1B correlates with cell proliferation; it is present in rapidly dividing embryonic tissues but is poorly expressed in nonproliferating, differentiated adult tissues. In aged, adult mice, increased hepatic expression of FoxM1B accelerates hepatocyte proliferation after partial hepatectomy, while in hepatocytes in intact liver the transgenic protein is inactive and has no effect on proliferation. This has lead to the suggestion that artificial enrichment of FoxM1B in the liver may be feasible as a gene therapy approach to treatment of liver dysfunction due to aging. To investigate the influence of FoxM1B on liver tumor formation we examined the effect of sustained enrichment of FoxM1B in the hepatocytes of mice treated with a diethylnitrosamine(DEN)/phenobarbital tumor induction protocol. Transgenic enrichment of FoxM1B in hepatocytes did not increase the proliferation rate in normal liver tissue even when the protein was localized to the nucleus. However, it did cause an increase in the proliferation rate and size of preneoplastic and early neoplastic lesions though having no effect on the total numbers of these lesions. As tumors progressed to hepatocellular carcinomas the additional transgenic FoxM1B protein had no effect on cell proliferation, and there was no increase in tumor burden compared to wild type animals. This suggests that the artificial enrichment of FoxM1B in the liver may not be tumorigenic in that organ.
FRI0509 The factors associated with anxiety/depressive disorders in behÇet’s disease patients
Authors: P. Ovcharov, T. Lisitsyna, D. Veltishchev, O. Seravina, O. Kovalevskaya, Z. Alekberova, E. Nasonov
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> The anxiety/depressive disorders (ADD) is a special psychopathological problem for Behçet's Disease (BD) patients. ADD has high rates in BD, but their causes aren't enough investigated. <h3>Objectives</h3> To determine the main factors associated with anxiety/depressive disorders in BD patients. <h3>Methods</h3> The investigation has been realised in accordance with the interdisciplinary program "Stress factors and mental disorders in immune-mediated inflammatory rheumatic diseases". 116 BD patients were enrolled in the study. The majority of patients were men (69,8%), natives of the North Caucasus (51,9%), with mean age (M±m) 33,3±0,98 years. All the patients met the criteria of the International Study Group for BD (1990) classification. The disease activity was assessed by scoring system BDCAF. ADD were diagnosed by psychiatrist in accordance with the ICD-10 in semi-structured interview. The severity of depression was evaluated by Montgomery–Asberg Depression Rating Scale (MADRS) and anxiety – by Hamilton Anxiety Rating Scale (HAM-A). The severity of stress was evaluated by PSS-10 scale. <h3>Results</h3> ADD were diagnosed in 87 BD patients (75%). The dysthymia (29,3%) and recurrent depressive disorder (21,5%) prevailed in these patients, generalised anxiety disorder (6,03%) and single depressive episode (7,76%) were rare. Cognitive disorders of different severity were diagnosed in 87 (75%) patients. The presence of ADD didn't depend on gender and duration of the disease. The factors associated with ADD were found during Pearson correlations. Then linear regression analysis was done and obtaining prognostic model showed that ADD was associated with: sleep disorders (β=0,401), asthenia (β=0,176), cognitive disorders (β=0,145), chronic stress (β=0,036) and stress severity (PSS-10 score) (β=0,115), age of eye damage (β=0,135), onset of ADD before BD onset (β=0,147), pure quality of life (QoL) estimated by visual analogue scale (VAS) (β=0,163), gastrointestinal BD symptoms (β=0,101), higher CRP level (β=0,174), younger age of patients (β=-0,053) and early childhood trauma (before 7 years old) (β=0,15) (area under the ROC curve=0,957) (figure 1). Figure 1 Area under the ROC curve=0957 <h3>Conclusions</h3> The results demonstrated high prevalence of ADD in surveyed BD patients. ADD in BD is much more associated with early childhood trauma, chronic severe stress, onset before BD, younger age of patients, older age of eye damage, gastrointestinal involvement, higher CRP level, accompanied by sleep disturbances, asthenia, cognitive disorders and had a negative impact on QoL. <h3>Disclosure of Interest</h3> None declared
AB0650 Thrombotic microangiopathy associated to anca-positives vasculitis: a french retrospective case control study and literature review
Authors: A. Dellal, Jean Jacques. Boffa, Eric. Rondeau, Pierre Yves. Hatron, Christophe. Deligny, Stephane. Bally, Olivier. Fain, Paul. Coppo, Arsène. Mekinian
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Objectives</h3> In this large nationwide French case-control study, we describe the features of TTP and ANCA-positive vasculitis; compare to vasculitis without associated TTP; describe the outcome and treatments. <h3>Methods</h3> We collected all cases with TTP and associated vasculitis. We conducted a literature review using PubMed, Web of Science, congress posters from January 2005 to August 2017 of PTT and ANCA-positive vasculitis. A control group of MPA without TTP during all the disease foillow-up was extracted from the Saint Antoine and Montfermeil Hospital patients with vasculitis. Firstly we compared our PTT cases and the literature review cases and secondary with a control group ANCA vasculitis without MAT. <h3>Results</h3> 8 patients with MAT secondary to ANCA associated vasculitides were included in our French series 75% of Women with a median age 45 years,<sup>21–76</sup> positive ANCA in 50% and 37.5% is MPO, BVSA score at 16, FFS at 1. In 10 literature cases 90% Women, a median age 60 years [17–77], positive ANCA in 100% and 30% is MPO, BVSA score at 39, FFS at 1. The clinical features at the diagnosis of vasculitis were fever (n=5; 62%), ENT involvement (25%), kidney cresescnt glomerular involvment (n=6; 75%) with kidney failure in joint involvement (n=2; 25%) polyarthralgia type, with gastrointestinal involvement type mesenteric ischemia and pericarditis and lung involvement (nodules and alveolar haemorrhage) (n=1; 12.5%), in one case each Median C- reactive protein levels were at 49 mg/L [1–204], with creatininemia at 170 mg/dl [80–588]. ANCA were present in 4 patients (50%), MPO in 3 cases (37.5%). The time between the diagnosis of vasculitis and TTP was 9 months [0–51]. TTP features were: Hb at 7.8 g/dl [4.8–10], LDH 1658 [777–3110], platelets 33000 [3000–1 25 000], haptoglobin at 0 [0–0.05], creatinine at 205 [80–757]. ADAMTS 13 levels were at 10 [1–138], and x patients have normal ADAMTS13 levels, with anti ADAMTS 13 antibodies in 1 case. Plasma exchanges were done in all patients with median of 10 exchanges [4–23], 37.5% are dialyzed. <h3>Conclusions</h3> In comparison to our cases, the literature patients have similar organs involvement, but median creatininemia levels and BVAS levels were higher in the literature cases. Considering TTP features, our cases have less frequent active vasculitis, less important creatinine levels and thus less recurs to kidney dialysis. In vasculitis associated with TTP, there was no significant differences in organ involvements, BVAS and FFS scales values, laboratory data and ANCA levels. Only creatininemia as expected was higer in vasculitis associated with TTP (225 Mmol vs 150 Mmol, p=0.0044). <h3>Disclosure of Interest</h3> None declared
Ex Vivo Co-Culture of AML Blasts and Bone Marrow Mesenchymal Stromal Cells to Accurately Predict the Clinical Efficacy of Cytarabine-Daunorubicin Treatment
Authors: Sukhraj Pal Singh Dhami, Andrea Tirincsi, Denis V Baev, Janusz Krawczyk, John Quinn, Eva Szegezdi
Journal: Blood (2018)
FRI0426 Response of the reactive species interactome to hypothermia induced raynaud’s attack in primary raynaud and systemic sclerosis
Authors: A. Eman Abdulle, A.M. van Roon, A.J. Smit, A. Pasch, M. van Meurs, H. Bootsma, B.O. Fernandez, M. Feelisch, H. van Goor, D.J. Mulder
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Although the exact etiology of systemic sclerosis (SSc) remains unknown, a current hypothesis is that reactive species (including reactive oxygen species (ROS), reactive nitrogen species (RNS and reactive sulfur species (RSS)) play an important role in the pathogenesis. In addition, the chemical interactions between these molecules, also known as the reactive species interactome, may lead to the formation of more harmful free radicals, thus leading to more damage. We have previously shown a rapid free thiol increase in SSc patients during a cooling and recovery experiment, however the implications of RNS and RSS in this process remain uncharacterized. <h3>Objectives</h3> The aim of the current study was to explore nitric oxide and sulfate response, as a measure of the unified reactive species interactome, during hypothermia induced Raynaud's attack in systemic sclerosis (SSc), primary Raynaud's phenomenon (PRP) and healthy controls (HC). <h3>Methods</h3> Healthy controls (n=10), PRP patients (n=10) and SSc patients (n=10), all aged ≥18 years, were included. All SSc patients fulfilled the ACR/EULAR 2013 criteria. Fingertip photoelectric plethysmography was performed during a standardised cooling and recovery experiment. Patient characteristics were obtained and blood was drawn at four predetermined time points (T0, T1, T2 and T3). In addition to the previously mentioned free thiols, the following markers were also measured: nitros(yl)ated species, nitrite, nitrate, sulfate and the vascular leakage related molecules angiopoietin-1 and angiopoietin-2). <h3>Results</h3> Our results revealed a significantly longer median duration of hypoperfusion and longer recovery time in SSc patients compared to PRP patients and HC. This coincided with stable levels of angiopoietin-1/angiopoietin-2 throughout the experiment. In regards to the thiol modification related molecules, (nitrate, nitrite and RXNO) an increased median level of nitrate (T2: median 29.6 µmol, range 21.99–41.70 µmol, p=0.041) was found in SSc patients. Correspondingly, the same trend was observed for the median plasma concentrations of sulfate (p&gt;0.05 at all time points). <h3>Conclusions</h3> We have previously shown an increase of free thiols in all patients during the reperfusion phase. This finding sheds new light on the possibility that processes related to oxidative thiol modification, are rapidly reversible. The current findings revealed also a trend in increased levels of nitrate and sulfate in SSc patients. Therefore, it is plausible that these markers of the redox system interact with one another through the same pathway, underlining the complexity of the redox interactome and suggesting potential novel approaches for therapeutic intervention. <h3>Disclosure of Interest</h3> None declared
Evolution in the Risk of Cataract Surgical Complications among Patients Exposed to Tamsulosin
Authors: Robert J. Campbell, Sherif R. El-Defrawy, Sudeep S. Gill, Marlo Whitehead, Erica de L.P. Campbell, Philip L. Hooper, Chaim M. Bell, Martin W. ten Hove
Journal: Ophthalmology (2019)
THU0682 Human histocompatibility antigens (HLA) class 1 in anterior uveitis patients with and without spondyloarthritis
Authors: A. Godzenko, I. Guseva, I. Razumova
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Anterior uveitis (AU) and spondyloarthritis (SpA) are associated with HLA-B27. Previous genetic studies in different populations demonstrated other associations, in particular, HLA, both common and different for AU and SpA <h3>Objectives</h3> To assess the relationship of HLA class I antigens with AU depending on the presence or absence of SpA <h3>Methods</h3> 148 pts with AU were typed. All pts were divided into 2 groups: 1–52 pts with confirmed diagnosis of SpA (AU +SpA), 96 pts – with other forms of AU (52 – idiopathic AU, 29 – viral AU, 2- multiple sclerosis,, 2 - toxoplasmosis, 1- sarcoidosis, 1- tuberculosis, 3- chlamydial AU, 2 - Behcet's disease, 3 - juvenile chronic arthritis, 1 - Fuchs′s heterochromic iridocyclitis). 150 healthy donors formed control group. Analysis of the distribution of HLA- class I antigens (loci A, B, Cw) was performed comparing 2 groups of patients with AU and each group with control. <h3>Results</h3> HLA-27 in the group of pts AU +SpA identified in 96.1% (50/52), in the group AU – in 40,6% (39/96), in control – in 7.3% (11/150). If HLA-27 was present in the genotype, the risk of developing of common pathology (AU +SpA) was OR=315,9 [95% CI 61,9–2176,7], p&lt;0,0000001, the risk of AU - OR=8,7 [95% CI 3,9–19,4], p&lt;0,000001. Among locus C antigens high frequency of Cw2 was identified in the groups AU +SpA and AU compared with control (64,0%, 36,3% and 10.0%, respectively): AU +SpA vs control - p&lt;0,000001, AU vs control, - p&lt;0 00 001. The occurrence of Cw7 was significantly lower in the group AU +SpA in comparison with control: 12.8% and 38.7%, p=0002. In the group AU the occurrence of this antigen was not significantly different from the control group and the group AU +SpA. <h3>Conclusions</h3> The analysis of the distribution of HLA class I antigens confirmed association of HLA- B27 with AU in Russian population. Other associations, except Cw2, were not identified. Such significant increase of Cw2 in two groups of pts with high frequency of B27 is natural due to the phenomenon of linkage disequilibrium for HLA-B27 and Cw2 antigens. Cw7 antigen can play a "protective" role in relation to SpA, because the frequency of this gene in the group AU was not reduced compared to control. <h3>Reference</h3> [1] Robinson PC, Claushuis TA, Cortes A, et al. Genetic dissection of acute anterior uveitis reveals similarities and differences in associations observed with ankylosing spondylitis. Arthritis Rheumatol.2015Jan;67(1):140–51. doi:10.1002/art.38873 <h3>Disclosure of Interest</h3> None declared
Deficiency of Mitochondrial Glycerol 3‐Phosphate Dehydrogenase Contributes to Hepatic Steatosis
Authors: Yi Zheng, Hua Qu, Xin Xiong, Yuren Wang, Xiufei Liu, Linlin Zhang, Xiaoyu Liao, Qian Liao, Zheng Sun, Qin Ouyang, Gangyi Yang, Zhiming Zhu, Jing Xu, Hongting Zheng
Journal: Hepatology (2019)

Mitochondrial glycerol 3-phosphate dehydrogenase (mGPDH) is an integral component of the respiratory chain, and recent studies have suggested that it plays an important role in hepatic glucose homeostasis. However, its function in hepatic lipid metabolism is unclear. Here, we identified a role for mGPDH in nonalcoholic fatty liver disease (NAFLD). Specifically, mGPDH expression and activity were lower in fatty livers from patients and mice with NAFLD (ob/ob, high-fat diet [HFD] and db/db). Liver-specific depletion of mGPDH in mice or mGPDH knockdown in cultured hepatocytes exacerbated diet-induced triglyceride accumulation and steatosis through enhanced lipogenesis. RNA-sequencing revealed that mGPDH regulated endoplasmic reticulum (ER)-related proteins and processes. mGPDH deletion exacerbated tunicamycin (ER stress inducer)-induced hepatic steatosis, whereas tauroursodeoxycholic acid (ER stress inhibitor) rescued mGPDH depletion-induced steatosis on an HFD. Moreover, ER stress induced by mGPDH depletion could be abrogated by the intracellular Ca2+ chelator 1,2-bis (2-aminophenoxy) ethane N,N,N´,N´-tetraacetic acid acetoxymethyl ester, mitochondrial permeability transition pore (mPTP) inhibitor cyclosporine A, or cyclophilin-D (Cyp-D) knockdown. mGPDH promoting Cyp-D ubiquitination was also observed. Finally, liver-specific mGPDH overexpression attenuated hepatic steatosis in ob/ob and HFD mice. Conclusion: mGPDH is a pivotal regulator of hepatic lipid metabolism. Its deficiency induces ER stress by suppressing Cyp-D ubiquitination, a key regulator of the mitochondrial Ca2+ conductance channel mPTP, and results in hepatic steatosis. mGPDH may be a potential therapeutic target for the treatment of NAFLD.
Abstract 19969: Cardiologists Accurately Predict Resuscitated Out-of-Hospital Cardiac Arrest Patients That Do Not Require Immediate Cardiac Catheterisation
Authors: Melanie Wittwer, Sunny Wu, John F Beltrame, Chris Zeitz, Margaret A Arstall
Journal: Circulation (2017)

Introduction: Emergency vs. delayed cardiac catheterisation (CC) continues to be the subject of considerable debate in resuscitated out-of-hospital cardiac arrest (OHCA). This study aimed to invest...
The Platelet Factor-4 (PF4)-Dependent p-Selectin Expression Assay (PEA) Is Highly Accurate for the Detection of Pathogenic HIT Antibodies: Results of a 440-Sample Prospective Blinded Study
Authors: Deepti M. Warad, Bethany T Samuelson Bannow, Curtis Jones, Shannon Pechauer, Brian R. Curtis, Daniel W. Bougie, Parisa R Khalighi, Diane E. Grill, Rachel Leger, Ruchika Sharma, Dong Chen, Richard H. Aster, David A. Garcia, Anand Padmanabhan
Journal: Blood (2018)
Treosulfan Conditioning for Allogeneic Transplantation in Multiple Myeloma Improved Overall Survival in Upfront Hematopoietic Stem Cell Transplantation — a Large Retrospective Study By the Chronic Malignancies Working Party of the EBMT
Authors: Charlotte Gran, Junfeng Wang, Hareth Nahi, Linda Koster, Goesta Gahrton, Christine Wolschke, Hermann Einsele, Maija Itälä-Remes, Didier Blaise, Dietger Niederwieser, Ellen Meijer, Eefke J. Petersen, Liesbeth C. de Wreede, Per Ljungman, Jean-Henri Bourhis, Hendrik Veelken, Dietrich W. Beelen, Matthias Stelljes, Armin Gerbitz, Patrice Ceballos, Jürgen Finke, Jakob R. Passweg, Noel-Jean Milpied, Martin Bornhäuser, Ibrahim Yakoub-Agha, Stefan Schönland, Laurent Garderet, Nicolaus Kroeger
Journal: Blood (2018)
Hyperinsulinemia drives hepatic insulin resistance in male mice with liver-specific Ceacam1 deletion independently of lipolysis
Authors: Hilda E. Ghadieh, Lucia Russo, Harrison T. Muturi, Simona S. Ghanem, Iyad H. Manaserh, Hye Lim Noh, Sujin Suk, Jason K. Kim, Jennifer W. Hill, Sonia M. Najjar
Journal: Metabolism (2019)