tbuckley/cabot-search huggingface dataset:
AB1128 SENSITIVITY AND SPECIFICITY OF THE AUTOMATED SQUEEZE TEST (GAENSLEN’S MANEUVER) FOR IDENTIFYING METACARPOPHALANGEAL SYNOVITIS BY MAGNETIC RESONANCE IMAGING
Authors: Diana Daniela Castañeda Martínez, David Vega Morales, Jorge Antonio Esquivel Valerio, Mario Alberto Garza Elizondo, Brenda Roxana Vázquez Fuentes, Dionicio ángel Galarza-Delgado
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> It is well known that an early diagnosis and treatment for Rheumatoid Arthritis (RA) prevents its complications, therefore there are many efforts to identify individuals at risk to develop RA. The Squeeze test has been used to detect synovitis in metacarpophalangeal joints, even though it is used in daily practice, there is a great variability in their performance among rheumatologists. [2] <h3>Objectives</h3> The aim of this study is to determine the diagnostic performance of the automated squeeze test (AST) on the metacarpophalangeal (MCP) joints to detect the presence of synovitis, edema, or erosions by magnetic resonance imaging (MRI) using the rheumatoid arthritis magnetic resonance imaging score (RAMRIS) in first-degree relatives (FDR) of RA patients, of whom clinically suspect arthralgia (CSA) in hands was suspected, as well as in RA patients. <h3>Methods</h3> It is an observational and cross-sectional study for a diagnostic test. A total of 60 patients, older than 18 years, were included and divided in three groups: CSA group: 22 with less than 1 year with arthralgia and required to be FDR of RA patients; early RA group: 22 patients who met ACR/EULAR 2010 Classification Criteria with less than 1 year with the disease; and late RA group: 16 patients who met ACR/EULAR 2010 Classification Criteria, with more than 1 year with the disease. The AST was performed in the 60 participants' dominant hand. The device was evaluated by MRI, which examined the same hand in the 60 patients. <h3>Results</h3> A total of 240 MCP joints were evaluated. The AUC for the total RAMRIS score &gt;10 was [0.480 (95% CI 0.301-0.617)<i> P</i>=0.597], for synovitis RAMRIS score &gt; 7 was [0.459 (95% CI 0.331-0.669)<i> P</i>=0.791], and for the presence of any synovitis by RAMRIS was [0.575 (95% CI 0.428-0.723)<i> P</i>=0.331]. For the RAMRIS synovitis score, the most sensitive and specific cut-off of the force by AST was 4.645 kg with a 66.7% sensitivity and 50% specificity. <h3>Conclusion</h3> The application of AST with a force of 4.645 kg, to exert pain in the dominant hand, is a sensitive and specific technique to establish MCP joint inflammation, compared with other automated methods that had been recently tested. <h3>References</h3> [1] van Steenbergen HW, Aletaha D, Beaart-van de Voorde LJ, et al. EULAR definition of arthralgia suspicious for progression to rheumatoid arthritis. Ann Rheum Dis 2017;76:491-6. [2] Vega-Morales D, Esquivel-Valerio JA, Arana-Guajardo AC. Automated squeeze test (Gaenslen's manoeuvre) to identify patients with arthralgia suspicious for progression to RA: improving time delay to rheumatology consultation. Ann Rheum Dis 2017;76:e40. <h3>Disclosure of Interests</h3> None declared
Abstract 13004: Fractalkine Promotes the Progression of Diabetes-Induced Cardiorenal Syndrome through Induction of Mitochondrial Dysfunction and Cell Apoptosis
Authors: Yulin Liao, Wanling Xuan, Bing Wu, Shengcun Guo, Liang Su, Zhi Zeng, Baihe Chen, Ci Chen, Jianping Bin, Kitakaze Masafumi
Journal: Circulation (2012)

Background: The prognosis of diabetes mellitus (DM)-induced cardiorenal syndrome (CRS) is poor and its pathogenesis remains elusive. We have reported that chemokine fractalkine (FKN) exacerbated he...
Suitable source of DNA for a blood-based test for EGFR mutations
Authors: Hideharu Kimura, Asao Sakai, Yuichi Tambo, Shunichi Tamori, Kazuo Kasahara
Journal: Cancer Research (2008)

3667  Purpose: Epidermal growth factor receptor (EGFR) mutations are strong determinants of tumor response to EGFR tyrosine kinase inhibitors (EGFR-TKIs). Because most patients who require EGFR-TKI therapy already have advanced disease at the time of diagnosis, it is difficult to obtain sufficient tumor DNA to allow detection of EGFR mutations by direct sequencing from tissue samples non-surgical obtained by non-surgical means, for example by biopsy during bronchoscopy. Therefore, it is important to establish a blood-based method of testing for EGFR mutations. The aim of this study was to determine whether serum or plasma, is a more suitable sourse of DNA for detection of EGFR mutations.  Methods: Blood specimens were collected from patients with advanced NSCLC, and plasma and serum were separated from them. The amount of DNA present in the serum and plasma obtained from 5 mL of blood was measuredby the use of real-time quantitative polymerase chain reactionamplification of the glyceraldehyde-3-phosphate dehydrogenase gene. EGFR mutations (exon 18 - 21) in DNA obtained from plasma and serum were detected by direct sequencing and a highly sensitive assay by using mutation-specific probes, EGFR Scorpion Kit (Dxs Ltd, Manchester, UK). Tumor tissue was also obtained at the time of diagnosis. The tumor tissue was analyzed for EGFR mutation status by direct sequencing. We compared the EGFR mutation status determined by analysis of the DNA in serum and plasma with mutation status determined by analysis of the tumor tissue as the standard.  Results: Blood and tissue specimens were collected from 21 patients. The amount of DNA in the serum was 5-fold higher in the plasma (median amount of DNAin the serum from a 5 mL blood specimen, 50.1 ng/5mL; median amount DNA in the plasma from a 5 mL blood specimen,10.8 ng/5mL). EGFR mutations were detected in tumor tissue from 7 patients (E746_A750del in 4, L747_T751del in one, L858R in one, and L861Q in one). Direct sequencing revealed the same EGFR mutations in plasma DNA as in their tumor tissue in 2 of the 7 patients, but no mutations were detected in serum DNA. The results of the highly sensitive assay showed the same EGFR mutation status in the tumor and both the serum and plasma in almost all patients.  Conclusions: Plasma is a better source of DNA for blood tests for tumor-derived genomic alterations than serum. A highly sensitive assay using mutation-specific probes is needed for clinical application.
PHI-55: (NCI#7427): A phase I study of halichondrin B analog (E7389) in combination with cisplatin (CDDP) in advanced solid tumors: A CCC, NCI/CTEP-sponsored trial (grant U01 CA 062505).
Authors: Marianna Koczywas, Heinz-Josef Lenz, Joanne E. Mortimer, Anthony B. El-Khoueiry, Paul Henry Frankel, David R. Gandara, Mihaela C. Cristea, Vincent M. Chung, Dean Lim, Karen L. Reckamp, Derick H. M. Lau, Wei Ye, L. Austin Doyle, Mary I. Carroll, Edward M. Newman
Journal: Journal of Clinical Oncology (2013)

2564 Background: E7389 is a structurally simplified synthetic macrocyclic ketone analog of the marine sponge natural product Halichondrin B, which inhibits microtubule dynamics via a novel mechanism characterized by suppression of microtubule growth, lack of effect on microtubule depolymerization, and sequestration of tubulin into nonfunctional aggregates. Methods: The goals of this trial were to determine the DLT, the MTD, and PK of E7389 (administered on days 1, 8 and 15 every 28 days) in combination with CDDP (administered on day 1 every 28 days) in patients (pts) with advanced solid tumors. The protocol was amended after dose level 4 (E7389 1.4 mg/m 2 , CDDP 60 mg/m 2 ) when it was not feasible to administer E7389 on day 15 due to neutropenia; the treatment schedule was changed to E7389 days 1 and 8 and CDDP day 1 every 21 days. Eligibility criteria included normal organ function and &lt; 2 prior chemotherapy regimens. Results: To date, 36 pts have been treated (E7389 0.7-1.4 mg/m 2 and CDDP 60-75 mg/m 2 ). Median age 61 years; 19 males; the most common tumor types were lung (8), pancreatic (5), head and neck (6). 36% ECOG 0, 56% ECOG 1, 8% ECOG 2; Median number of cycles was 3 (1 – 8). There were 3 pts with DLT’s on the 28-day cycle: gr 4 febrile neutropenia (1.0/60); gr 3 anorexia/fatigue/hypokalemia (1.2/60); and gr 3 stomatitis/fatigue (1.4/60). There were 3 pts with DLTs treated on the 21-day schedule: gr 3 hypokalemia/hyponatremia (1.4/60); gr 4 mucositis (1.4/60); and gr 3 hypokalemia (1.2/75). With 2 DLTs out of 6 pts at E7389 1.4 mg/m 2 and CDDP 60 mg/m 2 , E7389 was reduced, CDDP was escalated, and the MTD was determined to be E7389 1.2 mg/m 2 and CDDP 75 mg/m 2 (1 patient out of 6 with a DLT). At the MTD, protocol defined dose modifications or delays were required in 2 of the 6 patients by cycle 2. Notably, all DLTs were observed in patients exposed to at least 2 prior lines of chemotherapy. Two pts had an unconfirmed PR (pancreatic, breast) and 2 had a PR (esophagus, transitional bladder). Conclusions: On a 21 day schedule,E7389 in combination with CDDP appears well tolerated and showed preliminary activity. The MTD was determined to be E7389 1.2 mg/m 2 and CDDP 75 mg/m 2 . Clinical trial information: 00400829.
AB0699 EFFECT OF SWITCHING BETWEEN TUMOR NECROSIS FACTOR INHIBITOR IN SPONDYLOARTHRITIS
Authors: hedia ben abla, Sonia Rekik, Soumaya Boussaid, Samia Jammali, Hela Sahli, Elhem Cheour, Mohamed Elleuch
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> The introduction of new drugs, in particular tumour necrosis factor inhibitor (TNFi) has revolutionized the treatment of spondyloarthritis (SpA). Meanwhile, about 30% of patients do not react to first-line TNFi. To date,there is no recommendations available forthe treatment of SpA patients after first TNFi failure. <h3>Objectives</h3> In this study we assessed the effectiveness of a second and third biotherapy in patients with SpA with an inadequate response to previous TNFi and to analyze the survival of the second biotherapy <h3>Methods</h3> This study included patients with SpA who had had at least two biotherapies. Treatment response was noted at 3 months. At 6 months, we assessed the maintaining of effectiveness in Spa. We studied the elements of a good response to the second biotherapy. <h3>Results</h3> Our population of study included 30 SpA. During the second treatment, response rate was achieved by 80% after 3 months. No difference was noted between first and second TNFi among switchers. 86, 7%maintained response at twelve months. For axial forms, decrease in BASDAI was significant at 3 months. For peripheral forms, an improvement of the swollen and tender joint counts was observed and was significant at 3 months. Four patients have received a third TNFi. Response rate was achieved by all of them after 3 months. All of them maintained response at 6 months.The elements of a good response founded were;the early age of the SpA starting(&lt;30y.o), the high value of initial CRP,the use of ESSG criteria,the SpA type,the extra articular signs, the first biotherapy and the reponse at 3 months to it, the drugs taken when second biotherapy were initiated a low initial EVA and BASFI. <h3>Conclusion</h3> These real-life data show that, after discontinuation of a first TNFi, switching to a second biotherapy in SpA is related to significantly improving of clinical effectiveness compared to a first TNFi. <h3>References</h3> none <h3>Disclosure of interests</h3> None declared
PB1756 EFFICACY OF SALVAGE CHEMOTHERAPY REGIMENS IN PATIENTS WITH REFRACTORY OR RELAPSED ACUTE MYELOID LEUKEMIA SINGLE CENTER EXPERIENCE
Authors: K. Simeonova, V. Nikolova, E. Naseva, M. Stoychov, T. Yankova, M. Donchev, G. Arnaudov, G. Balazenkou, M. Guenova, B. Spasov
Journal: HemaSphere (2019)

Background: Although understanding in the pathology of AML has developed and a variety of new therapies to AML have been found recently, no response to induction therapy still happens in 20–40% and relapse after CR occurs in 50–70% of the patients, respectively, which are called refractory or relapsed AML (R/R AML) Thus, it is necessary to find effective therapies in treating R/R AML patients. Aims: To compare the remission rate and survival between CLARA and FLAG‐Ida salvage chemotherapy in treating patients with refractory or relapsed acute myeloidleukemia (R/R AML). Methods: 18 R/R AML patients with the following demographic and disease characteristics were treated in our center between 2017‐2018(Table 1.). 7 patients with mean age 46.71 years were treated by CLARA salvage chemotherapy as follows:30 mg/m2/day clofarabine (days 1–5); 1 g/m2/day cytarabine(days 1–5) and 300 mcg/day filgrastim (days 0–till neutrophille recovery). While 11 patients with mean age 50 yeras were treated by FLAG‐Ida: 30 mg/m2/day fludarabine(days 1–5), 2 g/m2/day cytarabine (days 1–5), 8 mg/m2/day idarubicine (days 1–5) and 300 mcg/day filgrastim (days 0–till neutrophille recovery). Results: CLARA salvage therapy achieved 57.1 % complete remission rate (CR) and 85.7% overall remission rate (ORR), which was better than FLAG ‐ Ida chemotherapy which realized 36.4% CR and 54.5% ORR. The 30‐day survival rate was higher in CLARA group 85.7% compared to 63.6 in FLAG‐Ida group and it seemed to realize a prolonged OS compared to FLAG – Ida (Table. 3) image Summary/Conclusion: In our small group of patients with relapsed/refracoty disease CLARA seemed to be a better tretment option than FLAG ‐ Ida related to both overall response rte and overal survival.
THU0355 IGURATIMOD MIGHT TREAT SCLERODERMA WITH INTERRUPTED EGR1/TGF-? LOOP
Authors: Qingran Yan, Lichong Shen, Daniel Morales-Cano, Xiaoxiang Chen
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Systemic sclerosis (SSc) is an autoimmune disease characterized with multiple organ fibrosis. Previous studies showed transcription factor early growth response 1 (Egr1) overexpressed in the lesional skin of SSc patients, as well as Egr1 inducible genes<sup>1</sup>. Egr1 forms a positive feedback loop with master pro-fibrotic cytokine TGF and thus promotes fibrosis. <h3>Objectives</h3> To investigate the anti-fibrotic effect of a novel DMARD iguratimod in scleroderma models and patient skin grafts. <h3>Methods</h3> We used iguratimod to treat TGF-stimulated human skin fibroblast, bleomycin induced mice, tight skin 1 (TSK-1) mice and SSc skin grafts. The bleomycin model contained pre-establish fibrosis and late onset treatment. The skin grafts came from three SSc patients and was planted into irradiated nude mice. <h3>Results</h3> Iguratimod down-regulated egr1 expression in human skin fibroblast, with decreased collagen production and a-SMA expression. Knocking down Egr1 in fibroblast could mimic these effects. Both oral and topical iguratimod could reduce dermal thickening and collagen deposition in bleomycin induced skin fibrosis. a-SMA (+) myofibroblast counts, as well as Egr1 (+) and/or TGF (+) fibroblast counts in iguratimod treated groups were significantly less than the controls. Similarly, topical iguratimod ameliorated fibrosis with deduced dermal thickening in TSK-1 mice. Of note, 5-week iguratimod local injection remarkably reduced collagen content in skin grafts from three SSc patients. Staining of Egr1 and TGF in skin tissue were inhibited after iguratimod treatment simultaneously. <h3>Conclusion</h3> We found the potential of iguratimod to treat SSc, which was characterized as an Egr1 inhibitor. Further clinical investigation is needed to establish its safety and efficacy. <h3>References</h3> [1] Bhattacharyya S, Sargent JL, Du P, et al. Egr-1 induces a profibrotic injury/repair gene program associated with systemic sclerosis. PloS one 2011;6(9):e23082 doi: 10.1371/journal.pone.0023082 [2] Chen SJ, Ning H, Ishida W, et al. The early-immediate gene EGR-1 is induced by transforming growth factor-beta and mediates stimulation of collagen gene expression. The Journal of biological chemistry 2006;281(30):21183-97 doi: 10.1074/jbc.M603270200 [2] Wu M, Melichian DS, de la Garza M, et al. Essential roles for early growth response transcription factor Egr-1 in tissue fibrosis and wound healing. The American journal of pathology 2009;175(3):1041-55 doi: 10.2353/ajpath.2009. <h3>Acknowledgement</h3> This work is supported by National Natural Science Foundation of China (81601401). <h3>Disclosure of Interests</h3> None declared
PF545 EASIX FOR PREDICTION OF SURVIVAL IN LOWER RISK MYELODYSPLASTIC SYNDROMES
Authors: A.M. A. Merz, U. Germing, G. Kobbe, A. Jauch, A. Radujkovic, M. Hummel, A. Benner, M. Merz, C. Müller‐Tidow, P. Dreger, T. Luft
Journal: HemaSphere (2019)

Background: Patients with myelodysplastic syndromes (MDS) are at risk of early death from cardiovascular complications due to the link between clonal hematopoiesis and endothelial dysfunction. EASIX (Endothelial Activation and Stress Index) is a novel marker of endothelial dysfunction that is calculated from serum creatinine, lactate dehydrogenase levels, and thrombocyte counts. EASIX has been established to predict endothelial complications after allogeneic transplantation. Aims: To analyze the impact of EASIX on the survival of patients with lower risk MDS and correlation with markers of endothelial activation. Methods: We investigated the impact of EASIX measured at first diagnosis on survival of lower risk MDS patients who received supportive treatment in two independent institutions: n = 100 (cohort I) and n = 338 (cohort II). Serum Angiopoietin‐2, suppressor of tumorigenicity (ST)‐2, soluble thrombomodulin (sCD141), interleukin (IL)‐18, IL37, S100A9, and HMGB1 were measured as markers of endothelial cell distress and inflammasomal activity and correlated to EASIX. Results: Univariate analysis showed that high EASIX was associated with shorter survival in both cohorts (Cohort I: hazard ratio (HR) per log2 increase: 1.50; 95% confidence interval (CI) 1.27–1.79; p‐value &lt; 0.001 / Cohort II: HR 1.31 [1.20–1.42]; p‐value &lt; 0.001). We visualized this continuous effect of EASIX by grouping patients into quartiles according to EASIX (Figure 1 A and B). Multivariate Cox regression analysis confirmed that EASIX remains a significant predictor of survival even after adjustment for age, sex, cytogenetic abnormalities and bone marrow blast counts (Cohort I: HR 1.35 [1.12–1.63]; p‐value = 0.002 / Cohort II HR 1.18 [1.08–1.29]; p‐value &lt;0.001]. Models including EASIX showed lower prediction errors over time. Serum levels of Angiopoietin‐2 correlated significantly with EASIX (Spearman's rank correlation = 0.455, 95%CI 0.264–0.616, n = 74). Due to the lack of correlation between EASIX and S100A9 or IL‐1b, we performed a pathway analysis including serum HMGB1 and IL37. We observed a strong intra‐pathway correlation of S100A9 with IL1b, IL18, IL37, and HMGB1, arguing for the validity of our serum analyses Summary/Conclusion: We introduce EASIX as an easily accessible predictor for survival in patients with low‐risk MDS in best supportive care. image
FRI0532 SONIC HEDGEHOG PROMOTES PROLIFERATION, MIGRATION AND INVASION OF FIBROBLAST-LIKE SYNOVIOCYTES IN RHEUMATOID ARTHRITIS VIA P38-MAPK SIGNALING
Authors: Shangling Zhu, Yiming Shi, Yuanmei Ye, Xiaoxue Feng, Jianlin Huang
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Abnormal activation of Sonic hedgehog (Shh) signaling has been found in synovium from patients with rheumatoid arthritis and inhibition of Shh signaling pathway suppresses the proliferation and migration of fibroblast-like synoviocytes in rheumatoid arthritis (RA-FLS). However, the mechanism how Shh signaling promotes tumor-like behavior of RA-FLS is not well elucidated. <h3>Objectives</h3> In this study, we aimed to investigate the effect of Shh on p38 MAP kinase signaling and hypothesized that Shh promotes proliferation, migration and invasion of RA-FLS via p38-MAPK signaling. <h3>Methods</h3> Cultured RA-FLSs were treated with Smoothened agonist (SAG) or IL-1β combined with Smoothened antagonist (Cyclopamine). The levels of phosphorylation of p38, its upstream kinases including TGFβ activated kinase 1 (TAK1), MKK3, MKK6 and downstream target MAPKAPK2 (MK-2) were determined by western blot. The functional state of p38 was determined using in vitro kinase assay. Cell proliferation was evaluated by Cell Counting Kit -8 assay. Cell migration and invasion were performed by Transwell assay. The expression of matrix metalloproteinase proteins (MMPs), IL-6 and IL-8 was examined by real-time PCR. <h3>Results</h3> SAG rapidly increased phosphorylation of p38, TAK1, MKK3, MKK6 and MK2 in RA-FLS and combination of SAG and p38 inhibitor significantly decreased the phosphorylation of these kinases (<i>P</i>&lt;0.01). Inhibition of Shh significantly decreased the levels of phosphorylation of p38, TAK1, MKK3, MKK6 and MK2 in IL-1β stimulated RA-FLS (<i>P</i>&lt;0.05). In vitro kinase assay showed that stimulation of SAG significantly increased the kinase activity, and the kinase activity was inhibited by p38 inhibitor. Furthermore, SAG increased cell proliferation, migration, invasion and production of MMP1, MMP3, MMP13, IL-6 and IL-8. However, these enhanced activities of RA-FLS were inhibited in the presence of p38 inhibitor. <h3>Conclusion</h3> The study indicates that Shh is associated with activation of p38 MAPK signaling in RA-FLS and Shh may promote the tumor-like behavior of RA-FLS via p38 signaling. <h3>Acknowledgement</h3> This work was supported by grants from the National Natural Science Foundation of China (81571584, 81701609). <h3>Disclosure of Interests</h3> None declared
Sepsis Attributed to Bacterial Contamination of Platelets Associated with a Potential Common Source — Multiple States, 2018
Authors: Sydney A. Jones, Jefferson M. Jones, Vivian Leung, Allyn K. Nakashima, Kelly F. Oakeson, Amanda R. Smith, Robert Hunter, Janice J. Kim, Melissa Cumming, Eileen McHale, Pampee P. Young, Joy L. Fridey, Walter E. Kelley, Susan L. Stramer, Stephen J. Wagner, F. Bernadette West, Ross Herron, Edward Snyder, Jeanne E. Hendrickson, David R. Peaper, Adi V. Gundlapalli, Charles Langelier, Steve Miller, Ashok Nambiar, Morvarid Moayeri, Jack Kamm, Heather Moulton-Meissner, Pallavi Annambhotla, Paige Gable, Gillian A. McAllister, Erin Breaker, Erisa Sula, Alison Laufer Halpin, Sridhar V. Basavaraju
Journal: MMWR Morbidity and Mortality Weekly Report (2019)

During May-October 2018, four patients from three states experienced sepsis after transfusion of apheresis platelets contaminated with Acinetobacter calcoaceticus-baumannii complex (ACBC) and Staphylococcus saprophyticus; one patient died. ACBC isolates from patients' blood, transfused platelet residuals, and two environmental samples were closely related by whole genome sequencing. S. saprophyticus isolates from two patients' blood, three transfused platelet residuals, and one hospital environmental sample formed two whole genome sequencing clusters. This whole genome sequencing analysis indicated a potential common source of bacterial contamination; investigation into the contamination source continues. All platelet donations were collected using apheresis cell separator machines and collection sets from the same manufacturer; two of three collection sets were from the same lot. One implicated platelet unit had been treated with pathogen-inactivation technology, and two had tested negative with a rapid bacterial detection device after negative primary culture. Because platelets are usually stored at room temperature, bacteria in contaminated platelet units can proliferate to clinically relevant levels by the time of transfusion. Clinicians should monitor for sepsis after platelet transfusions even after implementation of bacterial contamination mitigation strategies. Recognizing adverse transfusion reactions and reporting to the platelet supplier and hemovigilance systems is crucial for public health practitioners to detect and prevent sepsis associated with contaminated platelets.