tbuckley/cabot-search huggingface dataset:
THU0413 Normalisation of nailfold microvasculature after hematopoietic stem cell transplantation in severe systemic sclerosis
Authors: M. Boonstra, D.C. Noordhoek, L.J. Beaart-van de Voorde, T.W. Huizinga, J.K. de Vries-Bouwstra
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Microangiopathy in Systemic Sclerosis (SSc), as visualised by nailfold capillary microscopy (NCM), is a dynamic and sequential process. Uncontrolled case-reports and a case-series report possible improvement of nailfold microangiopathy after hematopoietic stem cell transplantation (HSCT). <h3>Objectives</h3> To evaluate differences in nailfold microvasculature in patients with severe SSc treated with HSCT and those treated otherwise. <h3>Methods</h3> Severe SSc was defined as fulfilling criteria of the ASTIS trial.<sup>1</sup> For included patients two treatment groups were defined: 1. Patients treated with HSCT, 2. Patients treated otherwise (including cyclophosphamide, methotrexate, mycophenolate mofetil and rituximab). All available capillaroscopy images collected prior to and after treatment were scored independently by two trained observers, blinded for treatment. Scoring included categorical scores (0=no changes to 3≥66% alterations per millimetre) for capillary loss, neoangiogenesis, haemorrhages, dilatations, giants, disorganisation, together with a qualitative pattern and a VAS score for overall severity of microangiopathy. <h3>Results</h3> In total 55 patients were included, of whom 33 were female, mean age was 50±13 years and median mRSS of 20.<sup>15–28</sup> Twenty-nine patients were treated with HSCT. After treatment categorical score of capillary loss was lower with HSCT (median score 1.0 vs. 2.0, p=0.04) and VAS scores for severity of microangiopathy were better with HSCT (50.0 vs. 67.3, p=0.03). Compared to controls, a typical SSc pattern was less frequent in patients treated with HSCT (n=12/22, 55%, vs. n=18/20, 90%p=0.01). In 25 patients (HSCT n=11, control n=14) images prior to treatment were available. Improvement in capillary loss (HSCT −0.5 [IQR −1 to 0] vs. control +0.3 [IQR −1.0 to 1.0] p=0.01;), dilatation (HSCT −1.5[IQR −2.0 to −1.0] vs. control 0.0 [IQR −1.0 to 0.5] p≤0.01) and VAS scores (HSCT median −32.5 [IQR −80.5 to −4.5] vs. - controls+2.0 [IQR −35.5 to +46.0] p≤0.01;) improved significantly more in the HSCT group. <h3>Conclusions</h3> In patients with severe SSc, microangiopathy as reflected by nailfold capillaroscopy images, is less severe after treatment with HSCT and shows more improvement over time compared to patients with severe SSc treated otherwise. In specific, improvement seems to be characterised by normalisation of the capillary diameter and capillary density. To our knowledge, this is the first study to report on changes in microangiopathy after HSCT in a controlled study design. <h3>Reference</h3> [1] van Laar JM, Farge D, Sont JK, Naraghi K, Marjanovic Z, Larghero J, et al. Autologous hematopoietic stem cell transplantation vs intravenous pulse cyclophosphamide in diffuse cutaneous systemic sclerosis: a randomized clinical trial. JAMA2014;311(24):2490–8. <h3>Disclosure of Interest</h3> None declared
Abstract 20761: Impact of Improving Inpatient Circadian Rhythm on Hospital Readmission
Authors: Richard V Milani, Jonathan K Wilt, Megan A Terral, Robert M Bober
Journal: Circulation (2017)

Background: Circadian rhythms are endogenous 24-hour oscillations in biologic processes driving nearly all physiologic and behavioral functions including locomotor activity, blood pressure, tempera...
Thiotepa-Based Conditioning Regimen Compared to Non-Thiotepa Conditioning Regimen Prior to Allogeneic Stem Cell Transplantation in β Thalassemia Major: Impact on Survival
Authors: Wanxia Tan, Yuelin He, Xiaoqin Feng, Xuedong Wu, Chunfu Li, Liao Jianyun, Zhiyong Peng, Yongsheng Ruan, Ge Hui, Xiaoting Liu, Yuqiong Ren
Journal: Blood (2018)
AB0379 Musculoskeletal involvements in giant cell arteritis
Authors: M. Tougorti, T. Ben Salem, M.S. Hamdi, M. Lamloum, I. Ben Ghorbel, M.H. Houman
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Joint involvement is frequent in Giant cell arteritis (GCA), mostly polymyalgia rheumatica (PMR). The aim of this study was to describe clinical features of joint involvement in GCA. <h3>Objectives</h3> To compare patients according to the presence or not of PMR. <h3>Methods</h3> A retrospective and descriptive study of 96 patients with GCA diagnosed between 2000 and 2015. ACR 1990 criteria were used for the diagnosis of GCA. Clinical, biological and histological features were recorded and analysed. <h3>Results</h3> Joint involvements were noted in 67 patients with GCA (69.8%); 34 women and 33 men. Mean age at diagnosis was 72.4±6.36 years. PMR was diagnosed in 45 patients (46.8%) and revealed the disease in two patients. Neck pain was noted in 48 patients. Twenty one patients (21.8%) complained of peripheral arthralgias which revealed GCA in five cases. Joint manifestations were associated to cardinal symptoms of GCA: headache (97%), jaw claudication (62%), scalp tenderness (49.3%) and ophthalmologic manifestations (36.9%). Erythrocyte sediment rate and C-reactive protein were high in 89.2% and 82.7% of cases respectively. Constitutional symptoms (60% vs 39.2%; p=0.042), jaw claudication (68.2% vs 47.1%; p=0.038) and neck pain (62.2% vs 39.2%; p=0.024) were significantly more frequent in patients with PMR. Peripheral arthralgias (28.9% vs 15.7%) were more frequent in patients with PMR without significant differences. Giant cell vasculitis on temporal arterial biopsy was more frequent in patients with PMR (57% vs 30%; p=0.037). Corticosteroids were given in 97% of patients while methotrexate was used in 20.9%. <h3>Conclusions</h3> PMR in patients with GCA seem to be associated to different joint manifestations. <h3>Disclosure of Interest</h3> None declared
AB0369 Adult-onset still’s disease treatment predictors at 1-year follow-up in a single rheumatologic centre experience
Authors: M. Giannotta, F. Cacciapaglia, M. Giannini, M. Nivuori, R. Fanizzi, G. Lopalco, G. Laselva, C. Scioscia, F. Iannone
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Adult-onset Still's disease (AOSD) is a rare systemic inflammatory disorder mainly characterised by persistent high spiking fevers, evanescent rash, and joint involvement. Data on the efficacy of biologic therapy in the management of AOSD<sup>1</sup> is increasing and represents a breakthrough in the management of patients with AOSD refractory to corticosteroids (CS) or conventional (c) DMARDs. <h3>Objectives</h3> We aimed to evaluate possible predictor on the need to use a biologic agent in the management of AOSD patients. <h3>Methods</h3> In this retrospective monocentric study we evaluated AOSD patients followed in our outpatient's clinic since 2010 with at least 1 year follow-up. Clinical manifestations, joint involvement, CS and c- or bDMARD use were main outcome measures. T-test or ANOVA and Chi-squared were used to compare continuous or categorial data, when appropriate, and the odds ratio (OR) for which condition had an influence on clinical outcome was calculated. <h3>Results</h3> We evaluated 28 AOSD patients (mean age 43±14 years; median disease duration 3 (95%CI 2.5–17.3) months). All patients at baseline were treated with a median CS of 18.7 (95%CI 14.3–24.8) mg/die prednisone equivalent dose, and median methotrexate (MTX) dose of 15 (95%CI 13.4–16.28) mg/week. After 1 year follow-up, in the 8 patients (28.6%) that needed to start a bDMARD (4 anti-IL1; 3 anti-IL6 and 1 anti-TNF), we observed that baseline joint involvement was the more prevalent manifestation of the disease with higher DAS28 compared to those patients still on CS +MTX (DAS28 3.8±1.2 vs 2.8±1.1, respectively p=0.03). Moreover, we showed that clinical manifestations of systemic involvement (i.e. fever, rash, organomegaly and anaemia) were associated with a protective risk to start a bDMARD at 1 year (OR 0.4 95% CI 0.2–0.76). Consistently, in those patients with concomitant elevated ESR (&gt;20 mm/h), CRP (&gt;15 mg/L) and ferritin (&gt;250 ng/ml) levels at baseline, we observed a low risk to start a bDMARD at 1 year follow-up (OR 0.4 95% CI 0.18–0.87). <h3>Conclusions</h3> In our cohort about one third of AOSD patients required to be treated with a bDMARD at 1 year follow-up, mainly if joint involvement was the predominant clinical manifestation at disease onset. Systemic manifestations of the disease seem to benefit from high dose CS+MTX combination therapy. Further studies with more extensive cases are necessary. <h3>Reference</h3> [1] Cavalli G, Franchini S, Aiello P, Guglielmi B, Berti A, Campochiaro C, Sabbadini MG, Baldissera E, Dagna L. Efficacy and safety of biological agents in adult-onset Still's disease. Scand J Rheumatol2015;44(4):309–14. <h3>Disclosure of Interest</h3> None declared
THU0224 Renacer study: efficacy and safety assessment of czp therapy in the treatment of 501 patients with rheumatoid arthritis(RA) among spanish population in clinical practice
Authors: V. Torrente-Segarra, M. Fernandez, R. Expósito, N.P. Garrido, A. Sanchez-Andrade, J.R. Lamua, A. Olivé, J.V. Tovar
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Certolizumab PEGol (CZP) differs from other anti-TNFs in that it is monovalent and it lacks the Fc region found in monoclonal antibodies. CZP is also PEGylated. Its efficacy in patients with rheumatoid arthritis (RA) has been evaluated in previous clinical trials. <h3>Objectives</h3> The purpose of the current study is to assess effectiveness, safety and survival rate in patients with RA after 12 months of treatment and also within specific subgroups, in clinical practice settings. <h3>Methods</h3> Observational longitudinal prospective study of RA patients from 40 sites in Spain. Variables (baseline, 3- and 12 month assessment): socio-demographics, smoking status, previous synthetic DMARD (sDMARD) and biological DMARD (bDMARD) use; TJC, SJC, ESR, CRP, DAS28. Response variables EULAR Moderate/Good Response and DAS28 remission and Safety were assessed. Descriptive, comparative and Logistic regression analyses were performed. Kaplan-Meier survival curve was performed. <h3>Results</h3> A total of 501 patients were included: 78.6% women, mean age 53.6 year (±13.2 SD) and 77% were aged &lt;65 year Mean disease duration 7.5 year (±7.3 SD) and 27.7% having early RA. Baseline features are shown in table 1. Mean number of prior sDMARD 1.5 (±1.1 SD). Mean number of prior bDMARD was 0.8 (±1.2 SD). Mean duration of exposure to CZP was 9.8 months (±3.4 SD); Concomitant steroids intake 12.6%, sDMARD 24.2% and sDMARD plus steroids 54.9%; Smoking status: 69.8% never smoked, 12.9% former smoker and 17.3% current smoker. Baseline predictors of response: lower prior number sDMARD; low number prior bDMARD; higher CRP, ESR, TJC, SJC and DAS28 (p&lt;0.05) scores. Patients&lt;65 year had shown better DAS28 Remission rates as well as those who had previously received &lt;2 sDMARDs, those who were “bionaïve” at CZP initiation and those who used CZP in combination. CZP survival rates are shown in <i>Figures 1</i> and <i>2</i>. Adverse effects from treatment were reported in 65 patients (13%), mostly mild. <h3>Conclusions</h3> CZP showed benefit in active RA patients, with clear improvement in all clinical parameters, mostly in &lt;65 yo patients and those who had received low number of previous sDMARD and bDMARD. Survival rate at 12 month assessment was high, demonstrating a reasonable safety profile. <h3>Reference</h3> [1] Torrente-Segarra V, et al; (RENACER StudyGroup). RENACER study:Assessment of 12-month efficacy and safety of 168 certolizumab PEGol rheumatoidarthritis-treated patients from a Spanish multicenter national database. ModRheumatol2015Nov 7:1–6. <h3>Disclosure of Interest</h3> None declared
Predominant expression of human Slitrk6 in medulloblastomas
Authors: Naoki Yokota, Junkoh Yamamoto, Masayo Koide, Shaoyi Li, Tsutomu Tokuyama, Hiroki Namba, Katsuhiko Mikoshiba, Jun Aruga
Journal: Cancer Research (2005)

3616  Slitrk family proteins are characterized as integral membrane proteins that have two leucine-rich repeat (LRR) domains and a carboxy-terminal domain that is partially similar to trk neurotrophin receptor proteins. The LRR domains are similar to those of slit proteins. It was previously shown that mouse Slitrk genes are expressed predominantly in neural tissue and have neurite-modulating activity in cultured neuronal cells. Their expression profiles as well as their functions vary among the family members. Human Slitrks expression was also investigated in various types of brain tumor tissue. The results showed that all Slitrk genes are differentially expressed in brain tumors, including astrocytoma, oligodendroglioma, glioblastoma, medulloblastoma, and supratentorial primitive neuroectodermal tumor (PNET), especially Slitrk6 expression was highly selective in medulloblastoma and PNET. We confirmed high expression of Slitrk6 in several medulloblastoma cell lines in mRNA and protein level. It was also immunohistochemically examined that Slitrk6 was expressed mainly in membrane and cytosol of the tumor cells. These results suggest that the human Slitrk6 are useful molecular indicator of medulloblastoma properties.
Incidence of Acute Graft-Versus-Host Disease and Survival after Allogeneic Hematopoietic Cell Transplantation over Time: A Study from the Transplant Complications and Chronic Malignancies Working Party of the EBMT
Authors: Hildegard T. Greinix, Dirk-Jan Eikema, Linda Koster, Olaf Penack, Ibrahim Yakoub-Agha, Silvia Montoto, Christian Chabannon, Jan Styczynski, Arnon Nagler, Marie Robin, Stephen Robinson, Yves Chalandon, Malgorzata Mikulska, Stefan Schönland, Zinaida Peric, Annalisa Ruggeri, Francesco Lanza, Mohamad Mohty, Grzegorz W Basak, Kroger Nicolaus
Journal: Blood (2018)
NG2 antigen is a therapeutic target for MLL-rearranged B-cell acute lymphoblastic leukemia
Authors: Belen Lopez-Millan, Diego Sanchéz-Martínez, Heleia Roca-Ho, Francisco Gutiérrez-Agüera, Oscar Molina, Rafael Diaz de la Guardia, Raúl Torres-Ruiz, Jose Luís Fuster, Paola Ballerini, Ute Suessbier, Cesar Nombela-Arrieta, Clara Bueno, Pablo Menéndez
Journal: Leukemia (2019)

B cell acute lymphoblastic leukemia (B-ALL) is the most common childhood cancer, with cure rates of ∼80%. MLL-rearranged (MLLr) B-ALL (MLLr-B-ALL) has, however, an unfavorable prognosis with common therapy refractoriness and early relapse, and therefore new therapeutic targets are needed for relapsed/refractory MLLr-B-ALL. MLLr leukemias are characterized by the specific expression of chondroitin sulfate proteoglycan-4, also known as neuron-glial antigen-2 (NG2). NG2 was recently shown involved in leukemia invasiveness and central nervous system infiltration in MLLr-B-ALL, and correlated with lower event-free survival (EFS). We here hypothesized that blocking NG2 may synergize with established induction therapy for B-ALL based on vincristine, glucocorticoids, and l-asparaginase (VxL). Using robust patient-derived xenograft (PDX) models, we found that NG2 is crucial for MLLr-B-ALL engraftment upon intravenous (i.v.) transplantation. In vivo blockade of NG2 using either chondroitinase-ABC or an anti-NG2-specific monoclonal antibody (MoAb) resulted in a significant mobilization of MLLr-B-ALL blasts from bone marrow (BM) to peripheral blood (PB) as demonstrated by cytometric and 3D confocal imaging analysis. When combined with either NG2 antagonist, VxL treatment achieved higher rates of complete remission, and consequently higher EFS and delayed time to relapse. Mechanistically, anti-NG2 MoAb induces neither antibody-dependent cell-mediated not complement-dependent cytotoxicity. NG2 blockade rather overrides BM stroma-mediated chemoprotection through PB mobilization of MLLr-B-ALL blasts, thus becoming more accessible to chemotherapy. We provide a proof of concept for NG2 as a therapeutic target for MLLr-B-ALL.
SAT0089 Initiating tofacitinib in a treat to target strategy for rheumatoid arthritis leads to blunted multi-biomarker disease activity scores as compared to anti-tumour necrosis factor agents
Authors: C. Wiesenhutter
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> The use of a treat-to-target (T2T) strategy for the management of rheumatoid arthritis (RA) leads to better outcomes<sup>1</sup> but requires the regular use of disease activity measures (DAMs) to make clinical decisions. The optimal DAMs that should be used for this purpose have yet to be determined. <h3>Objectives</h3> To assess the utility of various DAMs for clinical decision making at a rheumatology clinic implementing a T2T strategy, following the initiation of Tofacitinib (tofc) and anti-tumour necrosis factor (ant-TNFs) agents. <h3>Methods</h3> Patients at a community based rheumatology clinic (authors) undergo DAM assessments on a routine basis as part of the implementation of a T2T strategy. These assessments include conventional clinical assessments, DAS28CRP, and the CDAI, as well as the ultrasound power Doppler joint count (UPDJC)<sup>2</sup> and multibiomarker disease activity score (MBDA). Patients undergo regular assessments, and if found to be under inadequate control, changes are made in their clinical regimen, and then the patients are reassessed three to six months later. Clinical significance was determined by Paired-samples T tests. <h3>Results</h3> Over the past four years, Thirty nine patients at this clinic were determined to be under inadequate control and were started on tofc. Also, the last forty patients started on anti-TNFs at the clinic were assessed for comparison. The two groups of patients had similar demographics with a combined average duration of clinical disease found to be &gt;10 years. Sixty eight% of these patients were female, and 85% of patients were rheumatoid factor positive. Table I shows that all of the DAMs listed resulted in significant clinical responses with the exception that following the institution of tofc, the MBDA did not result in clinically significant improvement. When individual biomarkers from the MBDA were analysed, anti-TNFs therapy lead to significant reduction in six of twelve biomarkers (IL-6, TNF-R1, TNF-R2, MMP-2, SSA and CRP) whereas treatment with tofc lead to significant reduction of two (VCAM and Resisten) and borderline reduction in two (IL-6 and TNF-R1) and a significant increase in one (Leptin). <h3>Conclusions</h3> Several DAMs performed well with the exception of the MBDA after tofc therapy. The MBDA showed a blunted response when compared to other DAMs in the tofc treated group, as well as when compared to patients treated with anti-TNFs. This finding is most likely due to tofc's unique mode of action, as reflected in the relatively small number of biomarkers that decreased following treatment, and the fact that leptin significantly increased. <h3>References</h3> [1] Smolen J, et al. Ann. Rheum. Dis2010;69;631–637. [2] Shin-ya Kawashiri, et al. Rheumatology2011;50(5):962–965. <h3>Disclosure of Interest</h3> None declared
Validation of Melanoma Immune Profile (MIP), a Prognostic Immune Gene Prediction Score for Stage II–III Melanoma
Authors: Robyn D. Gartrell, Douglas K. Marks, Emanuelle M. Rizk, Margaret Bogardus, Camille L. Gérard, Luke W. Barker, Yichun Fu, Camden L. Esancy, Gen Li, Jiayi Ji, Shumin Rui, Marc S. Ernstoff, Bret Taback, Sarabjot Pabla, Rui Chang, Sandra J. Lee, John J. Krolewski, Carl Morrison, Basil A. Horst, Yvonne M. Saenger
Journal: Clinical Cancer Research (2019)

Abstract Purpose: Biomarkers are needed to stratify patients with stage II–III melanoma for clinical trials of adjuvant therapy because, while immunotherapy is protective, it also confers the risk of severe toxicity. We previously defined and validated a 53-immune gene melanoma immune profile (MIP) predictive both of distant metastatic recurrence and of disease-specific survival (DSS). Here, we test MIP on a third independent population. Experimental Design: A retrospective cohort of 78 patients with stage II–III primary melanoma was analyzed using the NanoString assay to measure expression of 53 target genes, and MIP score was calculated. Statistical analysis correlating MIP with DSS, overall survival, distant metastatic recurrence, and distant metastasis-free interval was performed using ROC curves, Kaplan–Meier curves, and standard univariable and multivariable Cox proportional hazards models. Results: MIP significantly distinguished patients with distant metastatic recurrence from those without distant metastatic recurrence using ROC curve analysis (AUC = 0.695; P = 0.008). We defined high- and low-risk groups based on the cutoff defined by this ROC curve and find that MIP correlates with both DSS and overall survival by ROC curve analysis (AUC = 0.719; P = 0.004 and AUC = 0.698; P = 0.004, respectively). Univariable Cox regression reveals that a high-risk MIP score correlates with DSS (P = 0.015; HR = 3.2). Conclusions: MIP identifies patients with low risk of death from melanoma and may constitute a clinical tool to stratify patients with stage II–III melanoma for enrollment in clinical trials.
Plerixafor for the Treatment of WHIM Syndrome
Authors: David H. McDermott, Diana V. Pastrana, Katherine R. Calvo, Stefania Pittaluga, Daniel Velez, Elena Cho, Qian Liu, Hugh H. Trout, João F. Neves, Pamela J. Gardner, David A. Bianchi, Elizabeth A. Blair, Emily M. Landon, Susana L. Silva, Christopher B. Buck, Philip M. Murphy
Journal: New England Journal of Medicine (2019)

Summ a r y WHIM syndrome (warts, hypogammaglobulinemia, infections, and myelokathexis), a primary immunodeficiency disorder involving panleukopenia, is caused by autosomal dominant gain-of-function mutations in CXC chemokine receptor 4 (CXCR4).Myelokathexis is neutropenia caused by neutrophil retention in bone marrow.Patients with WHIM syndrome are often treated with granulocyte colony-stimulating factor (G-CSF), which can increase neutrophil counts but does not affect cytopenias other than neutropenia.In this investigator-initiated, open-label study, three severely affected patients with WHIM syndrome who could not receive G-CSF were treated with low-dose plerixafor, a CXCR4 antagonist, for 19 to 52 months.Myelofibrosis, panleukopenia, anemia, and thrombocytopenia were ameliorated, the wart burden and frequency of infection declined, human papillomavirus-associated oropharyngeal squamous-cell carcinoma stabilized, and quality of life improved markedly.Adverse events were mainly infections attributable to the underlying immunodeficiency.One patient died from complications of elective reconstructive surgery.(Funded by the National Institutes of Health.)C XC chemokine receptor 4 (CXCR4), which binds CXC chemokine ligand 12 (CXCL12), is expressed on most leukocyte subsets and regulates leukocyte development and trafficking, among other activities. 1 In WHIM syndrome (warts, hypogammaglobulinemia, infections, and myelokathexis), autosomal dominant gain-of-function CXCR4 mutations impair CXCL12-induced receptor down-regulation, thereby increasing CXCR4 signaling. 2,3Hematologic consequences include myelokathexis and defective early B-cell and T-cell development, which result in panleukopenia, abnormal architecture of secondary lymphoid tissue, and immunodeficiency. [4]][11][12][13] Treatment includes granulocyte colony-stimulating factor (G-CSF) and immunoglobulin replacement; however, long-term efficacy remains undefined. 4,9 Moreover, G-CSF does not correct monocytopenia, lymphopenia, and hypogammaglobulinemia, and disabling bone pain and hematopathologic conditions may occur as a consequence of its use. 10Here, we evaluate the CXCR4 antagonist plerixafor as a mechanismbased treatment in patients with WHIM syndrome who cannot receive G-CSF.
CD19-Directed CAR T-Cell (CTL019) Product Viability and Clinical Outcomes in Non-Hodgkin Lymphomas and B-Cell Acute Lymphoblastic Leukemia
Authors: Elise A. Chong, Bruce L Levine, Stephan A. Grupp, Megan Davis, Don L. Siegel, Shannon L. Maude, Whitney Lynn Gladney, Noelle V. Frey, David L. Porter, Carl H June, Stephen J. Schuster
Journal: Blood (2018)