tbuckley/cabot-search huggingface dataset:
SAT0007 THE SUPPRESSIVE ACTIVITY OF PERIPHERAL BLOOD TREG REPRESENTS IMMUNOLOGICAL REMISSION IN RHEUMATOID ARTHRITIS PATIENTS
Authors: Korawit Kanjana, Parawee Chevaisrakul, Ponpan Matangkasombut, Karan Paisooksantivatana, Putthapoom Lumjiaktase
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Rheumatoid arthritis (RA) patients with sustained remission may have relapsed disease after DMARDs tapering. Many predictors such as multibiomarker disease activity, ultrasound and MRI for detecting subclinical synovitis have some role to be prognostic tools. However, their values are limit.<b><sup>1, 2</sup></b> The number of Foxp3+ Treg may indicate immunological status in some situation, but is controversial.<b><sup>3</sup></b> The Treg function may represent the different stages of RA <h3>Objectives</h3> This study aimed to determine the suppressive activity of Foxp3+ Treg from peripheral blood (PB) of RA patients with clinical remission compare with active RA. <h3>Methods</h3> In this cross-sectional study, blood samples were collected from RA patients with sustained clinical remission for at least 6 months and from active RA patients. The Treg and autologous conventional T cell were isolated from PB of the patients by using FACS sorting. Then the isolated cells were evaluated suppressive activity by co-culture suppression assay. <h3>Results</h3> The Treg of patients with sustained clinical remission (for more than six months) showed higher suppressive activity compared to Treg from active RA patients [57.24% versus 23.67%, <i>p</i> &lt; 0.0001, 95% CI; 20.88-44.01(showed in figure 1A)]. Moreover, the suppressive activity correlated with the degree of disease activity. When we analyzed in patients with DAS28 score &lt; 2.6 (remission), &gt;2.6-3.2 (low DAS), &gt;3.2-5.1 (moderate DAS) and &gt;5.1 (high DAS), the suppressive activity of Treg dependently decreased to the degree of disease activity [57.97%, 39.15%, 23.01%, and 17.07%, respectively (showed in figure 1B)]. <h3>Conclusion</h3> This suppressive activity of Treg may indicate immunological remission in RA patients with clinical remission, especially in patients who candidate for DMARDs reduction. <h3>References</h3> [1] Schett G, Emery P, Tanaka Y, et al. Tapering biologic and conventional DMARD therapy in rheumatoid arthritis: current evidence and future directions. Annals of the Rheumatic Diseases. 2016;75(8):1428 [2] Hirata S, Dirven L, Shen Y, et al. A multi-biomarker score measures rheumatoid arthritis disease activity in the BeSt study. Rheumatology. 2013;52(7):1202-1207. [3] Kleinewietfeld M, Hafler DA. The plasticity of human Treg and Th17 cells and its role in autoimmunity. Seminars in Immunology. 2013;25(4):305-12. <h3>Acknowledgement</h3> This study was supported by a research scholarship from the National Research Council of Thailand and by Mahidol University. <h3>Disclosure of Interests</h3> None declared
Results of a phase II study of capecitabine-based doublets in the treatment of metastatic triple-negative breast cancer (mTNBC).
Authors: Ying Fan, Binghe Xu, Yuqian Liao, Fei Ma, Peng Yuan, Jiayu Wang, Pin Zhang, Qing Li, Lixue Xuan, Yang Luo, Xiaoyan Ding
Journal: Journal of Clinical Oncology (2012)

e11538 Background: It is extremely important to identify proper cytotoxic agents for TNBC which had limited choices except chemotherapy. Capecitabine are well established as a major chemotherapeutic agent in metastatic setting. The efficacy of capecitabine-based chemotherapy has not been prospectively studied in TNBC and data remains scant. This study was designed to investigate the efficacy of capecitabine-based doublets in the treatment of metastatic TNBC. Methods: Eligible metastatic TNBC women with measurable diseases were recruited to receive either TX regimen (docetaxel 75mg/m 2 iv d1 plus capecitabine 1000mg/m 2 bid, d1-14,q3w) or NX regimen (vinorelbine 25mg/m 2 iv d1, 8 plus capecitabine 1000mg/m 2 bid, d1-14, q3w) at the discretion of physicians for up to 6 cycles, until disease progression or unacceptable toxicity. The primary endpoint was objective response rate and secondary endpoints included progression free survival (PFS), overall survival (OS). Results: 45 mTNBC patients, 27 in TX and 18 in NX were recruited, mostly (73.3%) as 1 st line and the remaining as the 2 nd line. The total objective response rate was 20.0% and clinical benefit rate was 62.2%. After a median follow-up of 28 months, PFS was 5.2 months (95%CI, 4.1-6.3mons) and OS was 18.2months (95%CI, 8.7-27.7mons). Almost half of the patients (22/45) progressed during treatment or within one month of the treatment discontinuation. PFS was significantly longer if patients got CR/PR (9.6 vs 4.3mons, P=0.015). When comparing two doublets, the response rate was numerically but not statistically lower in TX group than in NX group (14.8% vs 27.8%, P=0.449). Similarly, no difference was found in either PFS (4.9 vs 5.2 mons, P=0.483) or OS (21.5 vs 18.3 mons, P=0.964) between two regimens. Conclusions: Although the overall survival seems to be reasonable, efficacy of capecitabine-contained TX or NX regimen was relatively poor in terms of tumor remission and progression free survival in mTNBC patients, suggesting capecitabine may have limited potency in this subtype. These two combinations may be considered to be acceptable but may not be recommended as prior choice for mTNBC patients.
Curcumin suppresses interleukin‐6 production in THP‐1 monocytes induced by <i>Propionibacterium acnes</i> extracts via downregulation of Toll‐like receptor 2 expression and the nuclear factor kappa B pathway
Authors: C. Xu, R. Zeng, Q. Chen, L. Du, J. Tong, Y. He, H. Xu, M. Li
Journal: British Journal of Dermatology (2019)
A multicenter multinational study of abdominal candidiasis: epidemiology, outcomes and predictors of mortality
Authors: Matteo Bassetti, Elda Righi, Filippo Ansaldi, Maria Merelli, Claudio Scarparo, Massimo Antonelli, Jose Garnacho-Montero, Ana Diaz-Martin, Inmaculada Palacios-Garcia, Roberto Luzzati, Chiara Rosin, Leonel Lagunes, Jordi Rello, Benito Almirante, Pier Giorgio Scotton, Gianmaria Baldin, George Dimopoulos, Marcio Nucci, Patricia Munoz, Antonio Vena, Emilio Bouza, Viviana de Egea, Arnaldo Lopes Colombo, Carlo Tascini, Francesco Menichetti, Enrico Tagliaferri, Pierluigi Brugnaro, Maurizio Sanguinetti, Alessio Mesini, Gabriele Sganga, Claudio Viscoli, Mario Tumbarello
Journal: Intensive Care Medicine (2015)
PS1289 THE ATYPICAL LYMPHOCYTE COUNT: A NOVEL PREDICTIVE FACTOR FOR SEVERE DENGUE INFECTION
Authors: V. Abeysuriya, C. Choong, S. de Mel, B.U. Thilakawardana, P. de Mel, M. Shalindi, C. de Mel, L. Chandrasena, S.L. Seneviratne, E.‐S. Yap
Journal: HemaSphere (2019)

Background: Dengue haemorrhagic fever (DHF) and Dengue Shock Syndrome (DSS) are life threatening complications of DI which occur in a minority of patients. The early identification of these individuals is critical to guide clinical management. There is currently no validated laboratory test which can predict severe complications of DI. The Atypical lymphocyte count (ALC) is a research parameter generated on Sysmex FBC analysers which has been correlated with the presence of circulating atypical lymphocytes (AL). Pilot studies have suggested that the presence of AL may be associated with severe DI. Aims: We evaluated the utility of the ALC as a predictive factor for severe dengue related thrombocytopaenia as well as DHF and DSS. Methods: We prospectively collected data on patients admitted to Nawaloka Hospital Sri Lanka (NH) with DI between December 2016 and August 2018. DI was diagnosed based on a positive Non‐structural antigen 1 or dengue IgM antibody. ALC data were extracted from the Sysmex XS500i automated FBC analyzer from day of admission to day seven. Clinical data was recorded from medical records and the computerized data base maintained by NH. Statistical analyses were performed using SPSS version 20. Results: 201 patients were included in the study. DSS and DHF occurred in 6.5% (n = 13) and 6% (n = 12) of patients respectively. Patients with DHF and DSS as well as those with low Glasgow Coma Scale and respiratory compromise had a higher mean ALC on each day of FBC assessment compared to those without these complications. We detected a statistically significant negative correlation between the ALC on admission and platelet count on days five to seven (the period during which nadir thrombocytopaenia is expected in DI). [Spearmen's correlation; Day 5:‐0.485, Day 6:‐0.428, and Day 7:‐0.344] (P = 0.001) We performed Receiver Operator Curve (ROC) analysis to determine the predictive value of an admission ALC more than 0.5x 10 3 /L for severe thrombocytopaenia (defined as a platelet count less than 50 x 10 9 /l) on day five. We found that this ALC cut off had 90% sensitivity and 70% specificity for severe thrombocytopaenia on day 5. The positive and negative predictive values were 74.4% and 91.2% respectively. We also showed that patients with cardiac and abdominal ultrasonographic abnormalities had a higher mean ALC. Summary/Conclusion: We propose that an admission ALC of greater than 0.5 x 10 3 /L has a strong predictive value for severe thrombocytopaenia on days five to seven of DI. Our data also suggest that a higher ALC on admission maybe predictive for severe DI. ALC on admission maybe a valuable modality for early identification of patients at risk of severe dengue related complications. image
PS1091 TREATMENT OF ACTIVATED B‐CELL LYMPHOMA WITH RITUXIMAB,DOXORUBICIN,ETOPOSIDE,PREDNISOLONE/IFOSFAMIDE+CISPLATIN PLUS LENALIDOMIDE (R‐ACEP/ICL), CONFERS LONG PROGRESSION FREE AND OVERALL SURVIVAL RATES
Authors: M. Salamoon, M. Balti
Journal: HemaSphere (2019)

Background: gene profiling (GEP) revealed the main two types of DLBCL [the germinal center B‐cell (GCB) and the non‐germinal center or Activated B‐cell lymphoma(ABC)]. Immuno‐histochemistry plays an important role in differentiating between the two types using several algorithms, however, Hans algorithm and the improved Hans are considered the more reliable. Patients with GCB are still doing well in the era of type I and II anti‐CD20, however, ACB patients are experiencing bad prognosis with shorter progression free and overall survival rates, therefore, we have developed a high‐dense high intense protocol to treat those population with ABC. Aims: the study aims at evaluating a new dose intense chemotherapy in patients with ABC lymphoma with end points including progression free and overall survival Methods: this is a multicenter study Al Bairouni university cancer center in Damascus, Syria between 2013 and 2015 where we recruited 122 patients having ABC DLBCL confirmed by immuno‐histochemistry using the improved Hans algorithm. Patients received a dose dense protocol as follows: (Rituximab 375 mg/m 2 with Doxorubicin 75 mg/m 2 , Cyclophosphamide 1200 mg/m 2 , Etopdside 300 mg/m 2 and Prednisolone 1 mg/kg for 5 days) repeated every 21 days for 6 cycles with 5 days G‐csf support. Then partial and complete responders were given (Ifosfamide 4 gr/m 2 day 1–3 + Cisplatine 40 mg/m 2 day 1–3) for 4 cycles repeated every 15 days with 4 days G‐csf support. Lenalidomide 10 mg/d was given upfront lasting for 1 year. End‐points were progression free survival and overall survival at 5 years. Results: overall response rate (ORR) was documented in 118 patients (96.7%) (92 complete responders and 26 partial responders). 10 patients progressed at different stages of follow up with a progression free survival (PFS) of 88.6% (95% CI 83–94). However, 113 patients were found to still alive at 5 years with an overall survival (OS) rate of 92.6 (95% CI 86–97). In spite of G‐csf support, neutropenia of different grades was documented in 23 patients (18.8%). Acute and transient renal failure was observed and managed in 15 patients (12.2%) mainly in the first 6 cycles. Other side effects were manageable. Summary/Conclusion: ABC forms a special entity of DLBCL carrying a bad prognosis compared with GCB subtype. Progress was made using the R‐CHOP, however, results were still poor until the addition of Ibrutinib, Lenalidomide or Bortezomib to R‐CHOP in different trials which improved OS to exceed 90%. In this study, we present a dose intense protocol conferring a good PFS and OS rates with acceptable toxicity profile. However, a big randomized trials including both ABC and GCB patients in order to identify factors having bad impact on progression.
AB0587 CLINICAL MANIFESTATIONS OF BEHCET’S DISEASE DEPENDING ON GENDER: A REVIEW OF 425 CASES IN RUSSIA
Authors: Zemfira Alekberova, Tatiana Lisytsyna, Regina Goloeva
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> The gender-related differences in clinical course of Behcet's disease (BD) are well-established, and more severe course is usually observed among young males. <h3>Objectives:</h3> To analyze the effect of gender on the severity and clinical features of BD. <h3>Methods:</h3> The study included 425 patients (male – 285, female – 140) with BD (according to ISGBD 1990 and ICBD criteria 2014) [1, 2]. The male-to-female ratio was 2:1, the mean age was 33,2±10,2 yrs, the median of disease duration - 134,3 [60,0; 192,0] months. <h3>Results:</h3> BD severity depending on gender We observed the following gender-related differences in clinical manifestations of BD: males significantly more often had uveitis (74% vs 57%, p=0,0003), optic neuritis (11% vs 0%, p=0,0004), blindness (9% vs 2,5%, p=0,04); cutaneous lesions (89% vs 71%, p&lt;0,001), such as pseudo-folliculitis (53% vs 21%, p=0,001), positive pathergy test (39,6% vs of 24,3%, p=0,001); severe vascular involvement (vena cava and iliac vein thrombosis, deep vein thrombosis, arterial thrombosis and arterial aneurism) (27% vs 11%, p=0,001), cerebral sinus thrombosis (9% vs 3%, p=0,015) and genital ulcers (77,9% vs 67,1%, p=0,012) compared with females. Male BD-pts more often had HLA-B5(51)-positivity (67% vs 51,5%, p=0,007), higher BD activity (BDCAF - 3,71±2,02 vs 2,64±1,45, p&lt;0,001) and BD-severity (severe BD-course – 73% vs 39%, p&lt;0,001). Mortality rate in this BD cohort was 1,2%, and all 5 cases were young males aged under 30 years. <h3>Conclusion:</h3> An association of severe clinical manifestations (ophthalmological and vascular, such as large vessels and cerebral sinus thromboses), higher disease activity &amp; severity, as well <h3>Disclosure of Interests:</h3> None declared
Abstract 14800: Limited Accuracy of the New ASE/EACVI-Algorithm for Heart Failure With Preserved Ejection Fraction (VeeDIA-Study I)
Authors: Vidya Enait, Frank P Oosterveer, Anton Vonk Noordegraaf, Albert C van Rossum, Walter J Paulus, M. L Handoko
Journal: Circulation (2017)

In 2016 the ASE/EACVI published a new and simplified algorithm to evaluate LV diastology. Grading of diastolic dysfunction is now based on the E/A-ratio and the presence of elevated E/e’, indexed l...
PS1582 DECREASED PLATELET REACTIVITY IS ASSOCIATED WITH AN INFLAMMATORY STATUS IN PATIENTS WITH CANCER
Authors: J. Riedl, M. Salzmann, I. Pabinger, C. Ay
Journal: HemaSphere (2019)

Background: Decreased platelet reactivity was observed in cancer patients at high risk of venous thromboembolism (VTE) and death. Prothrombotic and inflammatory mechanisms have been suggested to cooperate in the development of VTE, representing represent the hallmark of thromboinflammation. Aims: To assess whether platelet reactivity is associated with inflammatory parameters in cancer patients. Methods: Platelet reactivity was determined by whole blood flow cytometry in 62 newly diagnosed cancer patients (median age [interquartile range, IQR]: 63 [54–70] years, 48 % female) at several time points during the first 6 months of chemotherapy (total number of samples analyzed: 179). We measured platelet surface P‐selectin and activated glycoprotein (GP) IIb/IIIa expression in vivo and upon ex vivo stimulation with agonists of protease‐activated receptor (PAR) −1, −4, and GPVI. C‐reactive protein (CRP) and fibrinogen levels were analyzed in plasma samples from the corresponding blood draws. Results: Platelet reactivity, as determined by percentage of platelets expressing activated GPIIb/IIIa on the surface, upon stimulation with different agonists, correlated with significantly lower levels of CRP and fibrinogen (Table 1). Platelet surface P‐selectin expression upon stimulation of the GPVI receptor also showed a significant inverse correlation with CRP and fibrinogen (Table 1). Platelet activation in vivo (i.e. without ex vivo agonist activation) did not correlate with CRP and fibrinogen levels (Table 1). Summary/Conclusion: Our data indicate that there is an inverse relationship between platelet reactivity and inflammatory status in cancer patients, whereby platelets of patients with increased inflammatory parameters are less reactive to stimulation with platelet agonists. Further research is needed to better understand underlying pathophysiological mechanisms. image
PB1799 HOW TO PREDICT EARLY PROGRESSION IN PATIENTS WITH DIFFUSE LARGE B CELL LYMPHOMA
Authors: A. Nakaya, K. Ishii, S. Fujita, A. Satake, T. Nakanishi, Y. Azuma, Y. Tsubokura, R. Saito, A. Konishi, M. Hotta, H. Yoshimura, T. Ito, S. Nomura
Journal: HemaSphere (2019)

Background: Even in the rituximab era, the survival rates of patients who obtain complete remission and later experience disease recurrence remain unsatisfactory. The treatment strategy for early progression has not been taken into consideration. Aims: The aims of the present retrospective study were to extract DLBCL patients with early progression and to detect characteristic findings. Methods: 530 patients diagnosed with DLBCL from April 2002 to November 2017 were enrolled in the study. Primary treatment included R‐CHOP or R‐CHOP‐like regimens. Early progression was defined as progressive disease or a transient response with disease progression within 6 months after completion of treatment. Results: Among 530 patients, 149 patients (28%) showed early progression. Survival of early progression patients were significantly worse (12.1 months vs 152.9 months, p = 3.26e‐66). In multivariate analysis, NCCN‐IPI, elevated LDH, and PS &gt;3 were significant factors affecting survival. Patients who received salvage ASCT(n = 16) showed better prognosis than patients without ASCT (30.5 months vs 10.6 months, p = 0.012). Summary/Conclusion: In the rituximab era, we could use NCCN‐IPI to identify patients at high‐risk of early progression. image
Increase of scabies infestations, Norway, 2006 to 2018
Authors: E Amato, LS Dansie, GM Grøneng, HS Blix, H Bentele, L Veneti, P Stefanoff, E MacDonald, HH Blystad, A Soleng
Journal: Eurosurveillance (2019)

Between October and December 2018, several clinicians in Norway reported an increase in scabies diagnoses. We compared data from the Norwegian Syndromic Surveillance System on medical consultations for mite infestations with scabies treatment sales data to investigate this reported increase. From 2013 to 2018, consultations and sales of scabies treatments had almost increased by threefold, particularly affecting young adults 15-29 years. We recommend to increase awareness among clinicians to ensure timely diagnosis and treatment.
Glutamate Decarboxylase 65 Signals through the Androgen Receptor to Promote Castration Resistance in Prostate Cancer
Authors: Yi Gao, Lu Chen, ZunGuo Du, WenChao Gao, ZhengMing Wu, XiuJuan Liu, Hai Huang, DanFeng Xu, QingQuan Li
Journal: Cancer Research (2019)

The transition from an androgen-dependent to a castration-resistant state is a critical event in the progression of prostate cancer. In this study, we compared metabolic pathways between isogenic human androgen-dependent and castration-resistant prostate cancer (CRPC) patient-derived xenograft models, and found consistent activation of the γ-aminobutyric acid (GABA) shunt in CRPC. This difference was the result of phosphorylation and activation of glutamate decarboxylase 65 (GAD65), which synthesizes GABA from glutamate by decarboxylation. Mechanistic investigation showed that GABA binds to and retains the androgen receptor (AR) in the nucleus by facilitating AR association with the nuclear zinc finger protein ZNHIT3. GAD65 knockdown decreased the growth of multiple established CRPC xenografts and markedly delayed the time to emergence of castration resistance. These data encourage exploring GAD65 as a therapeutic target for CRPC. SIGNIFICANCE: This study reports metabolic alterations that could be responsible for the development of CRPC and identifies the GABA-producing enzyme GAD65 as a potential new therapeutic target.See related commentary by Taylor and Watt, p. 4580.
Single-injecting, bioinspired nanocomposite hydrogel that can recruit host immune cells in situ to elicit potent and long-lasting humoral immune responses
Authors: Chiranjeevi Korupalli, Wen-Yu Pan, Ching-Yen Yeh, Po-Ming Chen, Fwu-Long Mi, Hung-Wen Tsai, Yen Chang, Hao-Ji Wei, Hsing-Wen Sung
Journal: Biomaterials (2019)
AB0778 IMPACT OF DISEASE IN A SPANISH POPULATION WITH PSORIATIC ARTHRITIS
Authors: Rubén Queiró Silva, Juan D. Cañete, Susana Gómez, Ana Cabez
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Patients with psoriatic arthritis (PsA) experience significant disability and reduced quality of life, resulting from the emotional distress and functional impairment associated with psoriatic skin lesions, as well as joint disease. Patient reported outcomes are important to evaluate healthcare interventions and to reflect the impact of PsA on patients' lives. <h3>Objectives:</h3> The aims of the present study were to describe disease characteristics of PsA patients with an acceptable symptoms state (PsAID score&lt;4) as well as to analyze predictive factors for PsAID&lt;4. <h3>Methods:</h3> Post-hoc analysis of data from a cross-sectional observational, multicenter study, aimed at evaluating the prevalence of MDA in a Spanish population with PsA, to describe their characteristics and to evaluate the association between MDA and the impact of the disease as assessed by the PsAID questionnaire. The original study included 227 adult patients of both genders diagnosed with PsA according to CASPAR criteria with at least one year of disease evolution and on treatment with biological and/or conventional synthetic disease modifying anti-rheumatic drugs (cDMARD). The PsAID questionnaire reflects the effect of PsA from the patient's perspective. It is composed of 12 physical and psychological domains. PsAID score &lt; 4 identified patient-acceptable symptoms state. <h3>Results:</h3> 122 patients with a PsAID score &lt;4 were included. Demographic and clinical characteristics of the study population are shown in Table 1. Overall, 53/102 (52.0%) and 83/122 (68.0%) patients presented articular or skin remission, respectively. 76/122 (62.3%) of patients were in MDA state; the majority presented a low disability state according to HAQ (85.2%). A moderate relationship between HAQ&lt;0.5 and PsAID&lt;4 (k=0.5325) and fair between MDA and PsAID&lt;4 (k=0.3594) were observed. Multivariate logistic regression analysis showed that patients with distal interphalangeal joint (DIP) involvement (odds ratio (OR) [95%CI], 0.402 [0.203-0.799]; p=0.009), family history of PsA (OR: 0.252 [0.089-0.716]; p=0.010) and increased CRP (OR: 0.922 [0.854–0.995; P = 0.036] were significantly less likely to reach a PsAID score&lt;4. <h3>Conclusion:</h3> There are discrepancies between the treatment goals (MDA) and the impact of disease as assessed by PsAID. Clinical characteristics such as DIP involvement, inflammatory load (PCR) and genetic factors (familial history) seem to be associated with a lower probability of being in an acceptable symptoms state in PsA patients. <h3>Disclosure of interests:</h3> Rubén Queiró Silva: None declared, Juan D. Cañete: None declared, Susana Gómez Employee of: I am a current employee of Pfizer., ana Cabez Employee of: Pfizer