tbuckley/cabot-search huggingface dataset:
PS1092 TANDEM AUTOLOGOUS HEMATOPOIETIC STEM CELL TRANSPLANTATION FOR TREATMENT OF ADULT T-CELL LYMPHOBLASTIC LYMPHOMA: A MULTIPLE CENTER PROSPECTIVE STUDY IN SOUTHWESTERN CHINA
Authors: Y. Liu, J. Li, J. Rao, Q. Wen, S. Wang, S. Lou, T. Yang, B. Li, L. Gao, C. Zhang, P. Kong, L. Gao, M. Wang, L. Zhu, X. Xiang, S. Zhou, X. Liu, X. Peng, X. Chen, J. Zhong, X. Zhang
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/m2 with Doxorubicin 75 mg/m2, Cyclophosphamide 1200 mg/m2, Etopdside 300 mg/m2 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/m2 day 1–3 + Cisplatine 40 mg/m2 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.
Chlorhexidine–alcohol versus iodine–alcohol for surgical site skin preparation in an elective arthroplasty (ACAISA) study: a cluster randomized controlled trial
Authors: T.N. Peel, M.M. Dowsey, K.L. Buising, A.C. Cheng, P.F.M. Choong
Journal: Clinical Microbiology and Infection (2019)
AB1218 ANALYSIS OF REFERRAL TRENDS TO A SECONDARY CARE RHEUMATOLOGY SERVICE FROM GENERAL PRACTICE, OVER A TEN- YEAR PERIOD
Authors: Ganesh Kasavkar, Kaushik Chaudhuri, Roxanne Mcvittie
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> The practice of Rheumatology in the UK has undergone significant change in the past decade. These have been driven by developments in our understanding of the diseases; early arthritis clinics; changing population demographics; changes in the health services (NHS) all of which have influenced referral patterns to rheumatology. <h3>Objectives:</h3> To analyse referral data from primary care three time points of a month at a time, over a decade – from 2006 to 2016 to assess changing trends, if any, of patients attending Rheumatology. <h3>Methods:</h3> We analysed referrals from the primary care in the months of Feb '06 (n=89), Aug'12 (n=50) and Feb'16 (n=100). We looked at the following: reason for referral and our response, referral to out-patient review interval; outcome and final diagnosis. We also analysed between first appointment and DMARD initiation in inflammatory arthritis. <h3>Results:</h3> <b>R</b>eferrals were grouped as demonstrated in the table below. The mean interval from Referral to patient review was 11.5 weeks in Feb 2006, 7.15 weeks in August 2012 and 6.6 weeks in Feb 2016. In patients with the diagnosis of inflammatory arthritis we also looked at mean timeframe from 1<sup>st</sup> review to initiation of DMARDs which is demonstrated in the chart below. <h3>Conclusion:</h3> Mean interval between primary care referral to first outpatient review has improved significantly over the period of 10 years Mean interval for DMARD initiation in inflammatory arthritis patients has also improved in the 10 years' time <h3> Disclosure of Interests:</h3> None declared
THU0370 PERFORMANCE OF THE ANKYLOSING SPONDYLITIS DISEASE ACTIVITY SCORE (ASDAS) IN PATIENTS WITH PERIPHERAL AND AXIAL SPONDYLOARTHRITIS IN CLINICAL PRACTICE
Authors: Esther Beckers, Marin Been, Casper Webers, Annelies Boonen, Peter Ten Klooster, Harald Vonkeman, Astrid van Tubergen
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> The Ankylosing Spondylitis Disease Activity Score (ASDAS) is a widely used composite measure of disease activity in axial spondyloarthritis (axSpA). Such a tool is lacking for peripheral SpA (pSpA). However, the ASDAS also assesses peripheral joint symptoms. Previously, trial data have shown that the ASDAS has high sensitivity to change and high discriminatory ability between disease states in pSpA (1). We hypothesized that the ASDAS can be used to measure disease activity in all patients with pSpA in clinical practice. <h3>Objectives</h3> To investigate the construct validity of the ASDAS in pSpA in comparison with axSpA in clinical practice. <h3>Methods</h3> Data from a registry for SpA in the Netherlands (SpA-Net) were used. Construct validity of the ASDAS was assessed by testing hypotheses about Spearman correlations with other outcomes measures including individual components of disease activity, physical functioning and health-related quality of life (HRQoL). Construct validity was also assessed by stratifying patients according to ASDAS cut-offs to compare means of different health outcomes across ASDAS states by one-way ANOVA analyses. All analyses were repeated after stratification for the presence/absence of psoriasis in pSpA. Results were compared to the performance of the ASDAS in axSpA. <h3>Results</h3> In total, 194 patients with pSpA and 222 patients with axSpA were included. Poor to high correlation was found between ASDAS and measures of disease activity (r<sub>s</sub>0.20 to 0.78), a moderate correlation was found between ASDAS and measures of physical functioning (r<sub>s</sub>0.61 to 0.64) and a poor to moderate correlation was found between ASDAS and measures of HRQoL in pSpA (r<sub>s</sub>-0.27 to -0.66) (table 1). With increasing ASDAS states, significantly worse scores were found on (other) measures of disease activity, physical functioning and HRQoL in pSpA (table 2). Stratification for the presence/absence of psoriasis showed similar results (data not shown). All results for pSpA were comparable to axSpA (see for example Table 1). <h3>Conclusion</h3> The ASDAS demonstrated similar construct validity in all patients with pSpA and axSpA in clinical practice. Therefore, the ASDAS can also be used to measure disease activity in pSpA in daily practice. <h3>Reference</h3> [1] Turina MC, et al. A psychometric analysis of outcome measures in peripheral spondyloarthritis. ARD 2016;75:1302-7. <h3>Disclosure of Interests</h3> None declared
Targeting pancreatic islet PTP1B improves islet graft revascularization and transplant outcomes
Authors: Hugo Figueiredo, Ana Lucia C. Figueroa, Ainhoa Garcia, Rebeca Fernandez-Ruiz, Christophe Broca, Anne Wojtusciszyn, Rita Malpique, Rosa Gasa, Ramon Gomis
Journal: Science Translational Medicine (2019)

Inhibition of tyrosine phosphatase PTP1B in mouse and human islets promotes islet revascularization and improves graft survival and function.
Identification of a Pan‐Gamma‐Secretase Inhibitor Response Signature for Notch‐Driven Cholangiocarcinoma
Authors: Colm J. O’Rourke, Matthias S. Matter, Chirag Nepal, Rui Caetano‐Oliveira, Phuongnga T. Ton, Valentina M. Factor, Jesper B. Andersen
Journal: Hepatology (2019)

Cholangiocarcinoma (CCA) mortality rates are increasing as a result of rising incidence and limited curative treatment(s) for patients with advanced disease. NOTCH pathway reactivation has been reported in biliary malignancies to conflicting degrees, hindering prioritization of key therapeutic targets within the network and identification of candidate responder patients for NOTCH-directed therapies. We analyzed genomic data from 341 patients with CCA and identified NOTCH1 significantly increased in a subgroup characterized by distinct stromal infiltration. Network-wide imbalance of the NOTCH pathway was seen in CCA, including correlation of NOTCH1 with NOTCH3 and NOTCH ligands. Given the diversity of observed NOTCH receptor engagement, γ-secretase modulation was rationalized as a therapeutic option. Indeed, subcutaneous transplantation of sensitive and resistant CCA cell lines pretreated with a γ-secretase inhibitor (GSi) cocktail demonstrated the antineoplastic effects of GSi in a subset of CCA and led to the development of a 225-gene responder signature. This signature was validated in an independent cohort of 119 patients. Further, this signature was enriched in liver tumors initiated by hydrodynamic injections of activated-NOTCH as compared with the AKT-RAS-driven tumors. Candidate GSi-responder patients were characterized by distinct transcriptomes overlapping with previous hepatobiliary metastasis and stemness, unique stromal properties, and dysfunctional intratumoral immune infiltration. Pan-cancer analysis identified 41.9% of cancer types to harbor prospective GSi-responder patients, which was adapted into a 20-gene GSi-sensitivity score metric capable of discriminating nanomolar versus micromolar sensitivity to a cell-permeable GSi (Z-LLNle-CHO) across 60 diverse tumor lines (area under the curve = 1). Conclusion: We have established a GSi-responder signature with evidence across several patient cohorts, as well as in vitro and in vivo models, to enable precision medicine application of NOTCH-directed therapy in CCA as well as prospectively across diverse malignancies.
Abstract 18156: Cardiac and Macrovascular Manifestation of Systemic Sclerosis (Scleroderma) - A Danish Nationwide Cohort Study
Authors: Sheraz Butt, Jørgen L Jeppesen, Christian Torp-Pedersen, Gunnar H Gislason, Søren Jacobsen, Charlotte Andersson
Journal: Circulation (2017)

Introduction: While many microvascular and cardiac manifestations of systemic sclerosis (SSc) are well-described, other macrovascular and cardiac complications are less well studied. We investigate...
Abstract 17604: Identification of Genotype-specific Electrocardiogram Patterns in Long QT Syndrome Using a Novel, Automated T Wave Analysis Program
Authors: Alan Sugrue, J. Martijn Bos, Vaclav Kremen, Bo Qiang, Paul A Friedman, Michael J Ackerman, Peter A Noseworthy
Journal: Circulation (2015)

Introduction: Congenital long QT syndrome (LQTS) is a sudden cardiac death-predisposing genetic disorder that has a characteristic electrocardiographic signature. Specific LQTS genotypes have been associated classically with different qualitative electrocardiographic ST - T wave patterns; however, clinical recognition of these patterns could be improved by an automated and quantitative method. We therefore aimed to use a novel, quantitative T wave morphological analysis technique from 12-lead surface ECGs to identify genotype specific LQTS ECG patterns. Methods: We analyzed a genotyped cohort of 420 patients (22 ± 15.7years, 43% male) with either LQT1 (61%) or LQT2 (39%). ECG analysis was conducted using a custom T wave program to automatically detect subtle changes in T wave morphology across all 12 Leads. Classification was performed using the top three T wave features in a linear discriminant classifier by 10x10 cross-validation. Results: The top three discriminant features were (1) a steeper T wave left slope for LQT1 in lead II (2950 vs 1700 mV/ms, p &lt; 0.0001), (2) a greater center of gravity in 1st segment of T wave in lead aVR in LQT1 (0.248 vs 0.209, p&lt;0.0001) and (3) a smaller Tpeak - Tend/QT ratio in lead aVR in LQT1 (0.20 vs 0.24, p&lt;0.0001). Using these top three features, we were able to successfully differentiate LQT1 and LQT2 in 79% of cases (figure 1). Conclusions: An automated morphological T wave analysis was able to discriminate between the two most common LQTS genotypes. This novel method enhances phenotypic characterization of LQT and could have a significant clinical impact on the diagnosis and management of patients with suspected LQTS.
Mechanism of the selective penetration of azurin derived peptides into cancer cells
Authors: Brad Taylor, Tohru Yamada, Fatima Lekmine, Konstantin Christov, Laura Bratescu, Ananda Chakrabarty, Craig Beattie, Tapas Das Gupta, Rajeshwari Mehta
Journal: Cancer Research (2007)

5623  The bacterial redox protein azurin preferentially penetrates a wide variety of human cancer cells, compared to normal cells. Azurin then forms a complex with the tumor suppressor protein p53, triggers apoptosis, and inhibits tumor growth. We have determined that the domain defined by aa 50-67 (p18) is the protein transduction domain (PTD) of azurin. Confocal microscopy and flow cytometry demonstrated that both p18 and a larger fragment, aa 50-77 or p28, selectively penetrate a variety of human cancer cell lines 5-20 fold compared to a corresponding “normal” cell line. The latter peptide also exerts specific cytostatic effects on selected cancer cell lines. The entry of either peptide is distinct from that of the prototypical cell penetrating peptides (CPPs) Arg8 and pTat, as heparan sulfate which facilitates cellular entry of Arg8 and pTat does not block cell penetration of either p28 or p18. Incubation of human melanoma (UISO-Mel2) cells with p18, p28 and Arg8 (control) in the presence or absence of specific inhibitors of cell internalization suggested that nystatin (inhibits caveolae formation) and brefeldin A (disruption of the golgi apparatus) significantly inhibited the entry of p18 into UISO-Mel2 cells by 15% and 40%, respectively. However, chlorpromazine (blocks clathrin-mediated endocytosis), cytochalasin D (inhibition of actin polymerization), taxol (inhibition of microtubule depolymerization), sodium azide (metabolic inhibition), or staurosporine (cell cycle inhibition) had no measurable effects on internalization of p18/p28. Confocal microscopy confirmed colocalization of p18 with golgin-97 and caveolin-1 confirming that both the golgi apparatus and caveolae play a role in membrane binding and intracellular transport of p18. In vitro saturation binding studies in UISO-Mel2 cells using 125I labeled azurin and unlabeled azurin, p28 or p18 suggest that azurin binds with high affinity (Kd =1.0 x 10-8M) and low capacity (87.3fmol/million cells) to the cell surface, and both peptides compete with azurin for the binding sites. These initial observations suggest that after azurin binding, the protein/receptor complex localizes in the caveolae (known sites of receptor-mediated endocytosis of various microbes and bacterial toxins) and is transported to the golgi apparatus by caveolar-mediated endocytosis (bypassing the lysosome pathway thereby avoiding degradation). Therefore, these novel small molecular weight peptides could potentially serve as CPPs to transport cargos and improve on current chemotherapies and diagnostic techniques or act as specific anti-cancer agents.
Synthesizing Speech From Brain Activity
Authors: Jennifer Abbasi
Journal: JAMA (2019)

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PB1760 CHARACTERISTICS OF DIAGNOSIS AND TREATMENT OUTCOME IN PATIENTS WITH ACUTE MYELOID LEUKEMIA OLDER THAN 60 YEARS-ANALYSES OF SINGLE CENTER
Authors: V. Popov, D. Georgescu, M. Andreescu, A. Arghir, I. Dumitru, S.M. Papuc, A.M. Iova, M. Begu, D. Soare, M. Omer, G. Ofiteru, O. Patrinoiu, F. Mihai, C. Despan, M. Popescu, M. Balea, R. Gogulescu, H. Bumbea
Journal: HemaSphere (2019)

Background: Patients with acute myeloid leukemia older than 60 years old have a poor prognosis and frequently are not fit for standard chemotherapy. Aims: We retrospectively analysed diagnosis characteristics and treatment outcome in order to identify particularities present in elderly acute myeloid leukemia (AML) group. Methods: We enrolled 62 AML patients older than 60 years diagnosed in Hematology Department Colentina Clinical Hospital between 2015-2019. The diagnosis of AML was made according to French-American-British Cooperative Group (FAB) classification combined with the 2008 revision of the World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia. Results: The median age was 70 years (range 72 to 76 years), and the male:female ratio was 1:1.The most frequent AML subtype was AML1 – 29 cases (46,77%) and in many cases AML was secondary myelodisplastic syndrome evolution – 38 cases (61%) Analysis of evolution data revealed an AML subgroup, consisting of 28 newly diagnosed patients, with a particular short survival – less than 2 months. Eleven patients from this subgroup were not treated due infection presence at diagnosis, this complication has negative influence of evolution of AML patients. In 17 patients we started treatment with hypomethylating agents (Azacytidina or Decytabina) and in 3 patients Mercaptopurine. The treatment outcome analysis identified 16 AML patients with unfavourable evolution due infection associated with severe neutropenia; 1 patient was lost due disease progression. Molecular diagnosis revealed FLT3-ITD mutation in 4 patients, 3 of them being lost immediately after diagnosis (1-2 moths). Cytogenetic results were available for 35 AML patients. The majority of patients had complex karyotype changes or other adverse or intermediate risk cytogenetics (25 out of 35 patients). The analyses of survival rate was performed by Kaplan Meier statistic method and used as endpoint the death and as analyses factors: the progression risk, treatment, presence of pancytopenia, infection. We obtained significant difference in patients group older than 75 years old who have infection – median survival rate 1 months (95%CI 1-8 mo) compared with those without infection 21 months (9-27mo), p = 0.05Summary/Conclusion: Acute myeloid leukemia diagnosed in our patients group was frequently secondary to MDS. Intermediate and high risk cytogenetic abnormalities were detected in a majority of these patients. Infection represent an important unfavourable factor in evolution and treatment outcome of patient older than 75 years
FRI0257 PROLACTIN AND DEHYDROEPIANDROSTERONE SULFATE IN WOMEN WITH ACTIVE SYSTEMIC LUPUS ERYTHEMATOSUS OF RECENT ONSET VERSUS CHRONIC INACTIVE PATIENTS
Authors: Olga Lidia Vera Lastra, Enzo Christopher Vazquez Jimenez, Maria del Pilar Cruz Dominguez, Luis Javier Jara
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Systemic lupus erythematosus (SLE) is an autoimmune disease, typically affecting young women at reproductive age. Prolactin (PRL) levels have shown direct correlation with clinical and serological disease activity. Hyperprolactinemia has been reported in a wide range of SLE patients (15–33%). Dehydroepiandrosterone (DHEA) and its sulfated form dehydroepiandrosterone sulfate (DHEAS) are the most abundant circulating steroid hormones in humans. The level of both metabolites is lower in patients with active SLE compared with patients with inactive disease, which suggests a potential role of low levels of DHEAS in the pathogenesis of SLE. <h3>Objectives:</h3> To evaluate serum PRL levels and DHEAS levels in patients with active SLE of recent onset vs patients with inactive chronic and healthy controls and their correlation with activity and chronicity scores <h3>Methods:</h3> Serum PRL levels and DHEAS levels were studied, as well as their correlation with SLEDAI and SLICC scores. Group 1: 15 patients with SLE of recent onset (active SLEDAI &gt;3) Group 2: 20 patients with inactive chronic SLE (SLEDAI&lt;3) and Group 3: 20 healthy controls. SLEDAI and SLICC were calculated in group 1 and group 2 respectively. PRL and DHEAS was measurement by radioimmunoassay in all groups. Statistical analysis: U-Mann Whitney and Spearman correlation. <h3>Results:</h3> Group 1: serum PRL levels were 27.82±9.96 ng/dl vs group 2: 20±5.02 ng/dl (p= 0.004) and group 3:19.58±4.57 ng/dl (p=0.004). Group 1: serum DHEAS levels were 14.58±9.26 μg/dl, group 2: 19.36±7.21 μg/dl (p=0.04) and group 3: 154.43±50.88 μg/dl (p =0.001). The average DHEAS was lower in patients with chronic SLE vs controls (p = 0.001). A positive linear correlation was found between serum PRL levels and SLEDAI score (Rho 0.92, p=0.001). No correlation was found between PRL and SLICC score. A negative linear correlation was shown between DHEAS concentration and SLICC score (Rho-0.46, p =0.03). <h3>Conclusion:</h3> PRL levels were higher in active SLE patients VS. chronic inactive SLE and healthy controls. In contrast, serum DHAS levels were lower in patients with active SLE vs. inactive chronic SLE. We found a positive correlation between SLEDAI score and PRL serum concentrations and an inverse correlation between SLICC score and DHAS serum levels. <h3>References:</h3> [1] Borba VV, Zandman-Goddard G, Shoenfeld Y. Prolactinand Autoimmunity. Front Immunol2018; 12:73. [2] Rutkowski K, Sowa P, Rutkowska-Talipska J, et al. al. Dehydroepiandrosterone (DHEA): hypes and hopes Drugs.2014;74:1195-207. [3] Robeva R, Tanev D, Andonova S, et al. Androgen receptor (CAG)n polymorphism and androgen levels in women with systemic lupus erythematosus and healthy controls. Rheumatol Int. 2013;33:2031-8. <h3>Disclosure of Interests:</h3> None declared