tbuckley/cabot-search huggingface dataset:
AB1302C SERUM IMMUNOGLOBIN G4 LEVEL IN DIFFERENT TYPES OF MALIGNANCY WITHOUT IMMUNOGLOBIN G4 RELATED DISEASE
Authors: Yanli Zhang, Zetao Liao, Yutong Jiang, LV Qing, Liudan Tu, Xinghua Guo, Zhiming Lin, Jieruo Gu
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> High levels of serum immunoglobulin G4 (IgG4) would comprise a useful diagnostic tool in IgG4-related disease (IgG4-RD), but little information is available about IgG4 in conditions other than IgG4-RD such as malignancies. Previous studies indicate that IgG4-RD is a strong risk factor for malignancy development. <h3>Objectives</h3> The aim of this study is to evaluate the level of serum IgG4 in different malignancy without IgG4-RD. <h3>Methods</h3> 90 patients with malignancy were enrolled between March 1<sup>st</sup> and August 30<sup>th</sup>, which have been excluded with IgG4-RD. All samples were collected before treatment. Diagnosis of malignancy was determined by histological result. The levels of serum IgG4 were determined by nephelometric assay. The cut-off value of serum IgG4 was 201 mg/dl. We compared the levels of serum IgG4 among patients with different types of malignancy. <h3>Results</h3> (1) Among the 90 patients, 18 patients were gallbladder carcinoma, 6 patients were lung carcinoma, 34 patients were liver carcinoma, 6 patients were gastrointestinal carcinoma, and 19 patients were pancreatic carcinoma. 68 (75.56%) patients were male and mean age was 52.8± 15.5 yrs. The mean value of serum IgG4 was 146.7±147.6 mg/dl, and 21 (23.3%) of patients have elevated serum IgG4. (2) Serum IgG4 level in gastrointestinal carcinoma is the highest (237.8±50.92 mg/dl), but the sample is too small. Serum IgG4 level in liver carcinoma was higher than other types of malignancy (180.5 ± 32.04 mg/dl. vs gallbladder carcinoma 114.4 ± 15.01 mg/dl, p&lt;0.01. vs pancreatic carcinoma 91.63 ± 19.89 mg/dl, p&lt;0.01. vs lung carcinoma 67.47 ± 11.75 mg/dl, P&lt;0.01). <h3>Conclusion</h3> Elevated serum IgG4 level is common in patients with malignancies, while patients with liver carcinoma have significant higher serum IgG4 level than those with gallbladder carcinoma, pancreatic carcinoma and lung carcinoma. This suggests that IgG4 may have different role in different types of tumor. <h3>Disclosure of Interests</h3> None declared
PF281 CLI24–001: FIRST IN HUMAN STUDY OF SEL24/MEN1703, AN ORAL DUAL PIM/FLT3 KINASE INHIBITOR, IN PATIENTS WITH ACUTE MYELOID LEUKEMIA
Authors: F. Ravandi, S. Strickland, S. Solomon, A. Nazha, R. Walter, I. Valimberti, A. Tagliavini, C. Fiesoli, M. Binaschi, K. Brzozka, S. Baldini, S. Heeger, A. Pellacani
Journal: HemaSphere (2019)

Background: PIM kinases are oncogenic FLT3 targets expressed in acute myeloid leukemia (AML) cells. Increased PIM expression is found in samples of relapsed AML patients exposed to FLT3 inhibitors (FLT3i). There is preclinical evidence that PIM inhibition restores cell sensitivity to FLT3i, and that dual FLT3/PIM inhibition eradicates FLT3 ‐ITD+ primary AML cells. SEL24/MEN1703, a potent PIM/FLT3 dual inhibitor, showed a significantly broader spectrum of activity in AML cell lines and primary AML blasts, irrespective of FLT3 status compared to FLT3 or PIM inhibitors alone Aims: To determine the recommended phase 2 dose (RP2D), the PK profile and the single agent activity of SEL24/MEN1703 in relapsed/refractory or newly diagnosed AML patients (excluding APL) unsuitable to chemotherapy Methods: First in Human, open label, non‐randomized, multi‐center, dose‐escalation (DE) and cohort expansion (CE) study of oral SEL24/MEN1703. SEL24/MEN1703 is given orally, QD, FOR 14 days in a 21‐day cycle with cycles repeated until disease progression or unacceptable toxicity. Dose escalation follows a 3+3 design to identify the RP2D; CE at RP2D is planned to confirm the safety profile and assess single agent activity. Patients are eligible for the study regardless of mutations and/or prior FLT3i treatment; prior PIM inhibitors are not allowed. White blood count (WBC) of ≤30 x 10 9 /L is required at baseline. Key secondary objectives include PK profile and single agent anti‐leukemic activity; exploratory objectives include assessment of clinical activity in relevant AML subsets of patients (eg FLT3 mutated) Results: As of January 8th, 2019 (data cutoff), n = 17 patients were treated and the study is enrolling. In the RP2D expansion phase, the study (currently running in 5 US sites) will be expanded to approximately 40 sites in the US and EU Summary/Conclusion: SEL24/MEN1703, a first in class, oral dual PIM/FLT3‐ITD inhibitor, is completing the DE part of a two‐part FIH study in patients with relapsed/refractory or unfit newly diagnosed AML unsuitable to chemotherapy. The RP2D expansion phase is planned to involve either US and EU investigational sites. This is the first clinical trial testing a dual PIM/FLT3‐ITD inhibitor, potentially active in AML regardless of FLT3 status and able to overcome FLT3i resistance
Biology and Taxonomy of crAss-like Bacteriophages, the Most Abundant Virus in the Human Gut
Authors: Emma Guerin, Andrey Shkoporov, Stephen R. Stockdale, Adam G. Clooney, Feargal J. Ryan, Thomas D.S. Sutton, Lorraine A. Draper, Enrique Gonzalez-Tortuero, R. Paul Ross, Colin Hill
Journal: Cell Host & Microbe (2018)
THU0259 ULTRASOUND OF MAJOR SALIVARY GLANDS IDENTIFIES PATIENTS WITH MORE COMPLEX SALIVARY GLAND HISTOPATHOLOGY BUT NOT MILDER LESIONS
Authors: Chiara Baldini, Francesco Ferro, Nicoletta Luciano, Gianmaria Governato, Marta Mosca, Stefano Bombardieri, Valentina Donati
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Ultrasonography of major salivary glands (SGUS) has been proposed as a feasible and reliable tool for the assessment of parotid and submandibular glands inflammation and damage in Sjögren's syndrome (pSS). However, the relationship between major SGUS and labial salivary gland (LSG) histopathology is still unclear. Objectives: to investigate the correlation between SGUS abnormalities and LSG histopathology in patients newly diagnosed patients with pSS <h3>Methods:</h3> Consecutive patients suspected of having pSS were enrolled in this study. All the patients underwent a complete diagnostic work up. The echostructure of each gland on B-mode images was graded on a 5-point scale (0–4), and a SGUS score ≥2 was defined as pathological. Hypo-anechoic areas in the glands were defined as isolated (&lt;25% of the surface), localized (25-50%) and diffuse-scattered (&gt;50%). Hyperechoic bands present in more than 50% of the parenchyma were also recorded. An expert pathologist analyzed all the LGS samples assessing focus score (FS), number of foci and presence of ectopic germinal centers (GCs). <h3>Results:</h3> We included 115 pts (105 F: 10 M, mean age (SD) 54.8 (12.5) years). Out of them 51 were diagnosed with pSS and 64 represented the no-SS sicca controls. A SGUS score ≥2 identified pSS patients with a sensitivity of 62.7% and a specificity of 96.7%. SGUS score significantly correlated with FS (r=0.457**, p=0.000), number of foci (r=0.359**, p=0.000) and number of ectopic GCs (r=0.505**, p=0.000). However, the overall concordance between SGUS and LSG histopathology was moderate (Cohen's kappa =0.574). Thus, we specifically focused on 19/51 pSS "discordant" cases who presented normal SGUS findings but focal lymphocytic sialadenitis in their LSG biopsy. These "discordant" patients tended to present a lower FS (1.7±0.5 vs 2.6±1.5, p=0.04) and a significantly lower number of foci in their biopsies (2.7±1.6 vs 4.6 ±2.9, p=0.01) when compared to patients with both abnormal SGUS findings and LGS focal lymphocytic sialadenitis. <h3>Conclusion:</h3> SGUS and LSG histopathology showed only a moderate correlation in patients with pSS. SGUS may be useful to identify pSS patients with a more severe inflammatory LSG infiltrates, ultimately contributing to promote non-invasive phenotyping of multiple subsets in pSS. <h3> Disclosure of Interests:</h3> Chiara Baldini: None declared, Francesco Ferro: None declared, Nicoletta Luciano: None declared, Gianmaria Governato: None declared, Marta Mosca Paid instructor for: GlaxoSmithKline, Lilly, UCB, Stefano Bombardieri: None declared, Valentina Donati: None declared&nbsp;
Imaging of Aortic Valve Cusps Using Commissural Alignment
Authors: Ikki Komatsu, Jonathon Leipsic, John B Webb, Philipp Blanke, G Burkhard Mackensen, Creighton W Don, James M McCabe, Christopher Rumer, Christina W Tan, Dmitry B Levin, Mario Ramos, Gabriel S Aldea, Mark Reisman, Harindra C Wijeysundera, Sam Radhakrishnan, Janarthanan Sathananthan, Nicolo Piazza, Ran Kornowski, Danny Dvir
Journal: JACC. Cardiovascular imaging (2019)
Abstract IA6: Lgr5 stem cell-based organoids in human disease
Authors: Hans Clevers
Journal: Cancer Research (2017)

Abstract The intestinal epithelium is the most rapidly self-renewing tissue in adult mammals. We originally defined Lgr5 as a Wnt target gene, transcribed in colon cancer cells. Two knock-in alleles revealed exclusive expression of Lgr5 in cycling, columnar cells at the crypt base. Using lineage tracing experiments in adult mice, we found that these Lgr5+ve crypt base columnar cells (CBC) generated all epithelial lineages throughout life, implying that they represent the stem cell of the small intestine and colon. Lgr5 was subsequently found to represent an exquisitely specific and almost ‘generic’ marker for stem cells, including in hair follicles, kidney, liver, mammary gland, inner ear tongue and stomach epithelium. Single sorted Lgr5+ve stem cells can initiate ever-expanding crypt-villus organoids, or so called ‘mini-guts’ in 3D culture. The technology is based on the observation that Lgr5 is the receptor for a potent stem cell growth factor, R-spondin. Similar 3D cultures systems have been developed for the Lgr5+ve stem cells of human stomach, liver, pancreas, prostate and kidney. Using CRISPR/Cas9 technology, genes can be efficiently modified in organoids of various origins. Citation Format: Hans Clevers. Lgr5 stem cell-based organoids in human disease [abstract]. In: Proceedings of the AACR International Conference: New Frontiers in Cancer Research; 2017 Jan 18-22; Cape Town, South Africa. Philadelphia (PA): AACR; Cancer Res 2017;77(22 Suppl):Abstract nr IA6.
Abstract 141: A Case of Kawasaki Disease with Re-dilatation of a Coronary Artery Aneurysm after Regression
Authors: Kensuke Oka, Takaomi Minami, Tatsuya Anzai, Sadahiro Furui, Akiko Yokomizo, Tomoyuki Ishii, Tomoyuki Sato, Koichi Kataoka, Takanori Yamagata
Journal: Circulation (2015)

Background: In patients with Kawasaki disease (KD), re-dilatation of coronary artery lesions (CAL) after regression is very rare. Here we report a case of KD with CAL re-dilatation after regression. Case report: A 15-year-old boy was diagnosed with KD at 1 year of age and was treated with intravenous immunoglobulin (IVIG, 400 mg/kg х 5 days). On day 14, echocardiography revealed CAL on the right coronary artery (RCA) and left coronary artery (LCA). Coronary arteriographic findings were as follows: segment 1, 3 mm in diameter; segment 6, 5 mm in diameter. He was prescribed aspirin, ticlopidine, and warfarin for 3 years. When he was 3 years old, coronary angiography showed complete CAL regression. His medications were discontinued and he underwent routine follow-up by echocardiography on which the CAL were not seen. At 14 years of age, coronary CT revealed re-dilatation of the LCA. Coronary angiography showed the same findings: 7 mm in diameter at the bifurcation between the LAD and the left circumflex artery, while the other regions were intact. He restarted aspirin and warfarin. The mechanism of CAL re-dilatation remains unclear; however, it is very important to follow patients carefully and routinely using echocardiography and/or coronary computed tomography, especially in cases with a history of CAL.
Bicuspid Aortic Valve Stenosis
Authors: Colin M. Barker, Michael J. Reardon
Journal: JAMA (2019)

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PB2142 BUSULFAN/CYCLOPHOSPHAMIDE (BU/CY) COMPARED WITH HIGH‐DOSE MELPHALAN (HDMEL) AS CONDITIONING REGIMEN FOR AUTO STEM CELL TRANSPLANTATION OF MULTIPLE MYELOMA
Authors: C. Fu, S. Zhou, S. Jin, L. Yan, J. Shang, X. Shi, J. Wang, Y. Yao, D. Wu
Journal: HemaSphere (2019)

Background: High dose melphalan (HDMEL) represents the standard conditioning regimen before auto stem cell transplantation (ASCT) for multiple myeloma (MM). But melphalan was inconvenient to obtain in mainland China. Aims: We compared two groups of MM patients who received HDMEL and busulfan/cyclophosphamide (BU/CY) regiment followed by ASCT. Methods 105 patients newly diagnosed with MM in our center undergoing ASCT between May 2012 and August 2017 were enrolled. They were divided into two groups according to conditioning regimen (BU/CY vs. HDMEL). In BU/CY group, busulfan [0.6 mg/kg for those with creatinine clearance rate (CCR)≥60 ml/min and 0.5 mg/kg for CCR≥40 ml/min and &lt;60 ml/min] was administered q6 h on days ‐7∼‐5 (7.2 mg/kg and 6.0 mg/kg in total, respectively) and cyclophosphamide (1.8 g/m 2 for those CCR≥60 ml/min and 1.5 g/m 2 for CCR≥40 ml/min and &lt;60 ml/min) was given once on days ‐4∼‐3. In HDMEL group, melphalan (200 mg/m 2 ) was given one dose on day ‐2. Results: At a median follow‐up of 30 months (range 0∼74 months), the average overall survival (OS) and median progression‐free survival (PFS) in BU/CY group were 53.7 months [95% confidence interval (CI) 49.3∼58.1] and 59.0 months (95% CI 48.3∼69.7) respectively, showing no significant difference with that of HDMEL group [average OS: 52.6 month (95% CI 44.5∼60.8) and median PFS: 8.0 months (95% CI 46.9∼69.1) respectively]. No significant difference was found in incidence of pneumonia, fever, mucositis, abnormal liver function, abnormal renal function between BU/CY group and melphalan group. No VOD was observed during the research. Summary/Conclusion: BU/CY conditioning regimen for MM before ASCT is not inferior to the HDMEL regimen in the Chinese mainland population. The regimen is effective and the toxicity can be tolerated.
NPM1c alters FLT3-D835Y localization and signaling in acute myeloid leukemia
Authors: Alina Rudorf, Tony Andreas Müller, Cathrin Klingeberg, Stefanie Kreutmair, Teresa Poggio, Sivahari Prasad Gorantla, Tamina Rückert, Annette Schmitt-Graeff, Anina Gengenbacher, Peter Paschka, Claudia Baldus, Robert Zeiser, George S. Vassiliou, Allan Bradley, Justus Duyster, Anna Lena Illert
Journal: Blood (2019)
Abstract P253: Adiposity Indicators and Blood Pressure in South Asian Children and Adolescents
Authors: Adeleke Fowokan, Zubin Punthakee, Scott Lear
Journal: Circulation (2018)

Background: The prevalence of childhood obesity is increasing globally. This has severe implications for cardiometabolic risk including hypertension. South Asian children are particularly vulnerable given their unique phenotype which results in higher body fat at similar body mass index (BMI) levels compared to Europeans. As a result, we sought to explore the association between adiposity indicators and blood pressure, and to compare the strength of these indicators in determining hypertension in South Asian children and adolescents. Methods: Children ages 7-8 and 14-15 with South Asian origin were recruited from two Canadian cities. They were then assessed for height, weight and waist circumference (WC). Waist to height ratio (WHtR), and BMI were calculated. Body fat percentage was determined by bioelectrical impedance analysis. Blood pressure (BP) was assessed three times using an automated device. All variables (except body fat percentage) were transformed to z-scores using published standards. Unadjusted and adjusted (age, sex, household income, exposure to bullying or violence) logistic regression was used to explore associations between adiposity and hypertension. Subsequently, area under the curve (AUC) analysis was used to explore the strength of the adiposity metrics in determining hypertension. Results: This study consisted of 306 boys and 402 girls (n=762) with mean age 9.5 (S.D 3.2) years. Significant association were detected in unadjusted models between the adiposity indicators with systolic and diastolic hypertension (p&lt;0.0001 for all). In the fully adjusted model, the association between adiposity with systolic and diastolic hypertension remained after adjusting for covariates (p&lt;0.01 for all). BMI was the strongest predictor of systolic hypertension (AUC= 0.791), while body fat percentage was the strongest for diastolic hypertension (AUC= 0.712). The other indicators were within close ranges in their ability to predict both systolic and diastolic hypertension. Conclusion: Significant associations were observed between adiposity indicators and hypertension. Moreover, the adiposity indicators were observed to be strong predictors of hypertension in AUC analysis. This highlights the relationship between adiposity and hypertension, and suggests that BMI, WC, WHtR and body fat percentage are good indicators of hypertension in South Asian children.
FRI0441 LONG DISEASE DURATION PREDICTED NON-ALCOHOLIC FATTY LIVER DISEASE IN PSORIATIC ARTHRITIS
Authors: Grace Chup-Hei Ho
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Psoriasis is known to be associated with non-alcoholic fatty liver disease (NAFLD). Previously studies showed that patients with psoriatic arthritis (PsA) were of higher risk of developing NAFLD compared to non-PsA individuals. <h3>Objectives</h3> To study the prevalence of NAFLD among patients with PsA and factors predicting the development of NAFLD. <h3>Methods</h3> This retrospective study was carried out in a tertiary hospital. Adult patients (&gt;18-year-old) with PsA who attended rheumatology specialist outpatient clinic between 1st Jan 2016 and 31st Dec 2018 were included. Demographic and clinical (disease duration, comorbidities, investigation results and treatment profile) data of these patients were obtained. NAFLD was diagnosed by either imaging or histology. Logistic regression was used to identify factors predicting NAFLD. <h3>Results</h3> 223 patients (male 53%, female 47%) with a mean age of 58-year-old and mean disease duration of 10.5 years were included in the study. Patients with NAFLD (n= 58, 26%), compared to those without, tended to be older (mean age 59.0-year-old vs 57.6-year-old) and had higher proportion of male (64% vs 51%). Among the patients with NAFLD, 30 (51.7%) had transient abnormal liver function test but none resulted in hepatic failure or death. 10 patients (17.2%) had their treatment for PsA withheld or changed as a result of abnormal liver function due to NAFLD. Long disease duration (OR 1.005, p&lt;0.01), but not age, predicted NAFLD. In particular, those with disease duration of 10 years or more were of higher risk (OR 2.79, p&lt;0.001). Cardiovascular risk factors including hypertension, diabetes mellitus, dyslipidaemia, and established cardiovascular diseases were not found to be predictors of NAFLD among PsA. None of the treatment agents including steroid, conventional synthetic or biological disease modifying anti-rheumatic durgs (DMARDs) was found to be risk factor for NAFLD. <h3>Conclusion</h3> NAFLD was common among patients with PsA, though it seldom led to significant hepatic impairment or interruption of treatment of PsA. Patients with longer duration of psoriatic arthritis were at risk of developing fatty liver. Traditional cardiovascular risk factors, established cardiovascular diseases or use of any particular treatment agent were not found to be predicting factor of development of NAFLD in PsA. <h3>References</h3> [1] Aliment Pharmacol Ther. 2015Feb;41(3):293-300 [2] J Invest Dermatol. 2018Apr;138(4):760-767 <h3>Disclosure of Interests</h3> None declared
PF685 THE RELATIONSHIP BETWEEN TOTAL ANTIOXIDANT CAPACITY AND JAK2V617F MUTATION IN ESSENTIAL THROMBOCYTHEMIA
Authors: M.‐A. Gaman, C. Moisa, A.M. Gaman
Journal: HemaSphere (2019)

Background: Essential thrombocythemia (ET) is a BCR‐ABL1‐negative myeloproliferative neoplasm associated in 50–60% of cases with the presence of the JAK2V617F mutation. Several studies have revealed that oxidative stress induces a growth advantage to JAK2V617F‐ positive clones, but little is known about the antioxidant status of ET patients. Essential thrombocythemia (ET) is a BCR‐ABL1‐negative myeloproliferative neoplasm associated in 50–60% of cases with the presence of the JAK2V617F mutation. Several studies have revealed that oxidative stress induces a growth advantage to JAK2V617F‐ positive clones, but little is known about the antioxidant status of ET patients. Aims: To evaluate the total antioxidant capacity (TAC) in patients with ET and to investigate if there are any differences between JAK2V617F‐positive cases and JAK2V617F‐negative ET cases in terms of TAC. Methods: We evaluated patients diagnosed with ET according to the WHO criteria (2016 revised) vs. healthy subjects (control group). Patients were classified based on age, sex and JAK2V617F mutational status. Haematological and biochemical parameters, as well as bone marrow aspirate or biopsy, were analyzed. Detection of JAK2V617F mutation was performed by RT‐PCR. TAC was measured using a multi‐detection microplate reader FLUOstar Omega (reagents from Sigma‐Aldrich). Data analysis was conducted using the student T‐test and a p‐value ≤ 0.05 was considered statistically significant. The study was approved by the Ethics Committee of the University of Medicine and Pharmacy of Craiova, Romania, approval no. 79/23.02.2017. All subjects agreed to partake in the study and signed a written informed consent. Results: The study group involved 58 ET patients (mean age 59.72 ± 14.63 years, age range 22–82): 25 males (40.32%, mean age 55.77 ± 15.80 years, age range 22–82) and 37 females (59.68%, mean age 62.14 ± 13.30 years, age range 23–81). 36 patients (62.07%) were JAK2V617F‐positive and 22 patients (37.93%) were JAK2V617F‐negative. 7 patients (12.07%) had homozygous genotype and 29 patients (50.00%) had a heterozygous genotype. TAC was decreased in patients with ET compared with healthy subjects and in JAK2V617F‐positive vs. JAK2V617F‐negative cases ( p &lt; 0.05). We found no significant differences between sexes in terms of age (men = 55.77 ± 15.80 years vs. women = 62.14 ± 13.30 years, p = 0.1116) or TAC (men = 0.50 ± 0.04 mM/L vs. women = 0.49 ± 0.06 mM/L, p = 0.3043). Also, we did not record significant differences in terms of TAC between JAK2V617F homozygous genotype vs. JAK2V617F heterozygous genotype (0.48 ± 0.05 mM/L vs. 0.49 ± 0.06 mM/L, p = 0.1686). Summary/Conclusion: In patients diagnosed with ET, TAC is decreased compared to normal individuals. Also, the decrease in TAC is more expressed in JAK2V617F‐positive cases vs. JAK2V617F‐negative cases or controls. No significant differences in terms of TAC were found between sexes or JAK2V617F homozygous vs. heterozygous genotype.