tbuckley/cabot-search huggingface dataset:
SP0128 THE VARIOUS ROLES OF PATIENT PARTICIPATION IN HTA BY THE EXAMPLE OF IQWIG
Authors: Virginia Seiffart
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> The involvement of affected persons in preparing systematic reviews and HTA represents an established international standard of benefit assessment. The Institute of Quality and Efficiency in Health Care (IQWiG) is a professionally independent scientific Institute founded within the framework of the German Health Care Reform of 2004 as an establishment of the Foundation for Quality and Efficiency in Health Care. IQWiG provides benefit assessments addressing issues concerning the statutory health insurance services. Its responsibilities include among others the preparation of scientific reports, expert opinions and comments on quality and efficiency issues taking age, gender, and personal circumstances into account. <h3>Objectives:</h3> The goal of this presentation is to provide an overview on different paths of involvement of patients and affected persons at IQWiG. <h3>Methods:</h3> IQWiG"s legal basis and responsibilities are anchored in the Social Code Book Fifth Book – Statutory Health Insurance (SGB V) and have been adapted and extended several times in the course of further health care reforms. The Institute"s work is commissioned by the Federal Joint Committee or by the Federal Ministry of Health. The information for this presentation stems from IQWiG"s General Methods (currently in version 5.0), a publicly available paper provided on the Institute"s website, which explains the groundwork for its assessments. <h3>Results:</h3> The involvement of affected persons at IQWiG primarily takes place during the initial work on a report within the framework of patient-relevant outcomes and relevant subgroups. Moreover, involvement can also include partaking in hearings. Affected persons include in particular patients (represented by parents or relatives, when appropriate) as well as potential participants in prevention measures. Affected persons are found via the patient representation of the Federal Joint Committee, as well as national or local self-help organizations or groups, hospitals or medical practices, external experts or other routes. The involvement can consist of a personal consultation or providing information in writing (through questionnaires or reports on personal experience), in both cases with documenting potential conflicts of interest. <h3>Conclusion:</h3> As representatives of patients or self-help groups are sometimes not patients themselves and cannot directly account for symptoms or their impact on the quality of life, focus is placed on involving persons directly affected. Different assessments require distinct types of involvement depending on the available time and the confidentiality of the topic. <h3>Disclosure of Interests:</h3> None declared
PS1202 DIFFERENTIAL DIAGNOSIS OF CONGENITAL HEMOLYTIC ANEMIA OF NEONATES AND INFANTS IN JAPAN
Authors: H. Ogura, T. Utsugisawa, T. Aoki, A. Kinoshita, Y. Okamoto, T. Kawakami, T. Yamamoto, H. Kanno
Journal: HemaSphere (2019)

Background: As a reference center, we analyze erythrocyte membranes, enzymes, and hemoglobin for congenital hemolytic anemia (CHA) in cases that are not diagnosed using ordinary laboratory examinations, and we introduce genetic testing using a hemolytic anemia‐related gene panel. We analyzed 136 cases from 2016 to 2017, including 36 patients under 1 year of age and 100 patients aged 1 year and over. Consequently, a definitive diagnosis was obtained for 84% of patients aged 1 and over but for only 72% of patients under 1 year of age. Aims: We aimed to summarize the final diagnosis for hemolytic anemia in patients less than 1 year of age analyzed over 3 years from 2016 to 2018 and discuss the common clinical features and laboratory data of undiagnosed cases. Methods: We analyzed 58 infantile CHA casesusing the following laboratory tests: flow‐cytometric osmotic fragility (FCM‐OF) test, eosin 5’‐maleimide binding test, assay of 15 red blood cell (RBC) enzymes, reduced glutathione content, and isopropanol stability test for unstable hemoglobinopathy. For the cases with a difficult diagnosis, genetic analysis with target‐captured sequencing (TCS) using a gene panel of 74 genes related to CHA was carried out. Results: Among 58 infants with CHA, we diagnosed 30 cases (52%); there were 18 cases of hereditary spherocytosis (HS), 2 cases of hereditary elliptocytosis (HE), 1 case of hereditary pyropoikilocytosis, 4 cases of erythro‐enzymopathies, and 2 cases of unstable hemoglobinopathies. Among the 28 undiagnosed cases, 14 showed an elevated percentage of residual RBCs in the FCM‐OF test. These cases also showed abnormal RBC morphologies such as target cells, stomatocytes, and/or pyknocytes. We performed TCS for 4 of the 14 cases, but none harbored mutations such as PIEZO1 or KCNN4 . Of the 7 cases, which could be followed up to at the age of one year, all recovered from CHA within a year. Summary/Conclusion: Mild hemolytic anemia accompanied by stomatocytes and/or target cells is a typical clinical feature of dehydrated hereditary stomatocytosis (DHSt) in adults. We previously showed that FCM‐OF clearly discriminated DHSt from HS or HE (Utsugisawa et al., Blood 2017;130:929). In this study, approximately half of the infants with undiagnosed CHA showed similar RBC morphology and higher osmotic resistance with no causative gene mutations. We noticed that clinical pictures of these infants resembled the description of infantile pyknocytosis (IP), which is a transient neonatal hemolytic anemia with the characteristic RBC morphology. As IP cases follow a relatively benign clinical course, we propose that FCM‐OF may be used as a biomarker for the tentative diagnosis of IP.
Abstract 13051: Unbiased Estimate of Heritability of CAD Before and After Adjustment for Traditional Risk Factors in Five NHLBI Cohorts
Authors: Elias L Salfati, Jin Li, Liana Del Gobbo, Themistocles L Assimes
Journal: Circulation (2016)

Introduction: The relative contribution of traditional risk factors (TRFs) to the genesis of CAD remains uncertain. Cohort studies report a high population attributable risk for TRFs, but only a third of the GWAS loci for CAD mediate risk through TRFs. Furthermore, these loci explain a small fraction of the overall heritability of CAD based on twin studies making it unclear whether these patterns will persist and whether estimates from twin studies are inflated. Hypothesis: Unbiased estimates of narrow sense heritability ( h 2 ) of CAD using contemporary analytic techniques applied to very distantly related individuals prior to and after adjustment of TRFs have not yet been reported. We hypothesized that such estimates would confirm a high heritability of CAD and that a substantial proportion of the genetic variance would be independent of TRFs. Methods: We used ~7 million genome wide imputed single nucleotide polymorphisms (SNPs) and a mixed linear model implemented in Genome-wide Complex Trait Analysis to estimate the h 2 of CAD from genomic relatedness among participants of five prospective NHLBI cohorts - ARIC, CHS, FHS, MESA, and WHI. To guard against bias from differences in minor allele frequencies (MAF) as well as region-specific heterogeneity in linkage disequilibrium (LD) between variants used in our analyses and causal variants, we used MAF and LD stratified multicomponent genetic restricted maximum likelihood. We ran 2 models assuming a population prevalence of 8%. The first model was not adjusted for any covariates and the second was adjusted for all TRFs as well as use of antihypertensive and statin drugs. Results: We analyzed a total of 23,522 participants including 3520 that developed incident clinical CAD during follow up. CAD h 2 was 39% (±3.1%) in our unadjusted model and 32% (±3.2%) in our fully adjusted model. A large majority (~95%) of the heritability in both models was derived from common SNPs with MAF &gt;1%. Conclusions: CAD is a moderately heritable trait with a large fraction of its genetic variance being a result of processes unrelated to TRFs. Prior family based estimates of the h 2 of CAD do not appear biased upwards. Consistent with many other complex traits, a majority of the genetic variance can be explained by common SNPs with very modest effects.
OP0022 DO MRI-DETECTED EROSIONS IN PATIENTS WITH CLINICALLY SUSPECT ARTHRALGIA PREDICT PROGRESSION TO RHEUMATOID ARTHRITIS? A LONGITUDINAL STUDY
Authors: Fenne Wouters, Xanthe Matthijssen, Debbie Boeters, Robin Ten Brinck, Annette van der Helm - van Mil, Ellis Niemantsverdriet
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Radiographic joint erosions are a hallmark of Rheumatoid Arthritis (RA). MRI is more sensitive than radiographs in detecting erosions. It is unknown if MRI-detected erosions are predictive for RA-development in patients with Clinically Suspect Arthralgia (CSA). <h3>Objectives</h3> We investigated the prognostic value of MRI-detected erosions (any MRI-erosion, or MRI-erosion characteristics that were recently identified as specific for RA) in CSA. <h3>Methods</h3> Patients presenting with CSA (n=491) underwent contrast-enhanced 1.5T MRI of the wrist, metacarpophalangeal (MCP) and metatarsophalangeal (MTP) joints at baseline. MRIs were scored according to RAMRIS. Presence of any MRI-erosion (erosion score ≥1) and RA-specific erosion characteristics as identified previously (grade ≥2 erosions, erosions in MTP5, erosions in MTP1 if aged &lt;40) were studied with clinically apparent inflammatory arthritis development as outcome (median follow-up 17 months). Analyses were corrected for age, CRP, ACPA and MRI-detected inflammation. <h3>Results</h3> Erosions were present in 20.6% of patients. Presence of erosions was not associated with arthritis development (HR multivariable analysis 0.85 (95% CI 0.52-1.40)). Also the different erosion characteristics were not predictive in CSA-patients (grade ≥2 HR 1.29 (95% CI 0.40-4.14), erosions in MTP5 HR 0.89 (95% CI 0.38-2.09) and MTP1 if aged &lt;40 HR 0.98 (95% CI 0.23-4.21)). MRI-erosions were more prevalent in ACPA-positive than in ACPA-negative patients (32.3% versus 18.8%, p=0.02). However, no association with arthritis development was observed in both subgroups. <h3>Conclusion</h3> MRI-detected erosions in hands and feet of patients with CSA were not predictive for arthritis development. These data warn against overinterpretation of MRI-detected erosions in CSA. <h3>Disclosure of Interests</h3> Fenne Wouters: None declared, Xanthe Matthijssen: None declared, Debbie Boeters: None declared, Robin ten Brinck: None declared, Annette van der Helm - van Mil Grant/research support from: The research leading to these results has received funding from the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation programme (Starting grant, agreement No 714312) and from the Dutch Arthritis Foundation. The funding source had no role in the design and conduct of the study., Ellis Niemantsverdriet: None declared
AB0386 RESPONSE TO BIOLOGIC THERAPY IS INFLUENCED BY THE BODY MASS INDEX IN PATIENTS WITH RHEUMATOID ARTHRITIS
Authors: Hitoshi Kodera, Yoshiko Sato, Yoshifuji Matsumoto
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Biologic therapies have been bringing huge advantage in the treatment of rheumatoid arthritis, but response to the therapy is heterogeneous. The influence of the body mass index to the treatment is still controversial. <h3>Objectives</h3> To identify the factors influencing in the response to biologic therapy (bio naïve). <h3>Methods</h3> The analysis of the patients with rheumatoid arthritis who were initiated biologics therapy (bio naïve) between January 2011 to December 2016 in the rheumatology department of a hospital in Japan, was conducted. The effects were evaluated by EULAR response criteria after 6 months of biologic therapy, and factors influencing the response were analyzed in terms of the baseline characteristics (sex, age, disease duration, body mass index, tender joint count, swollen joint count, Patient's visual analog scale, Doctor's visual analog scale, erythrocyte sedimentation rate, C-reactive protein, Disease Activity Score in 28 joints, Modified Health Assessment Questionnaire, Methotrexate use, Prednisolone use). <h3>Results</h3> There were differences of baseline characteristics in disease duration and body mass index between the patients who achieved "Good or Moderate response" and "No response" of EULAR response criteria after 6 months of biologic therapy (table 1). The latter was more significant, and the difference was found among biologics (table 2). <h3>Conclusion</h3> Body mass index influence in the response to first biologic therapy in patients with rheumatoid arthritis. <h3>Disclosure of Interests</h3> None declared
Pathogenesis of medulloblastoma and current treatment outlook
Authors: Jaroslaw Jozwiak, Wieslawa Grajkowska, Pawel Wlodarski
Journal: Medicinal Research Reviews (2006)

Abstract Medulloblastoma is the most common malignant tumor of the cerebellum in children, with a tendency to metastasize via CSF pathway. Survival rate varies depending on several factors, but is rather favorable, with radiotherapy as the treatment of choice. Irradiation of the craniospinal axis results, however, in severe neuropsychological and psychosocial impairments pertaining to memory, attention, motor functioning, language, and visuospatial abilities. Precise mechanisms underlying the formation of medulloblastoma are still unclear, but implication of at least three signaling molecules is postulated: insulin‐like growth factor‐I, WNT, and Sonic hedgehog. Thanks to increasing knowledge on the cellular mechanisms contributing to tumor formation, it is possible to propose new therapies that could replace radiotherapy or allow decreasing irradiation doses. The current review presents recent developments in medulloblastoma pathophysiology research and proposed inhibitors that could constitute good candidates for further pharmacological research. © 2006 Wiley Periodicals, Inc. Med Res Rev, 27, No. 6, 869–890, 2007
Abstract 20077: Diagnostic Accuracy of Quantitative Flow Ratio - A Wire-free Fractional Flow Reserve Derived From Diagnostic Coronary Angiography
Authors: Lukasz Koltowski, Jakub Maksym, Martyna Zaleska, Mariusz Tomaniak, Dominika Puchta, Grzegorz Opolski, Janusz Kochman
Journal: Circulation (2017)

Background: Fractional flow reserve (FFR) is the gold standard of functional assessment of intermediate lesions. Interrogating the stenosis with pressure-wire prolongs procedure, increases costs an...
Epacadostat plus pembrolizumab versus placebo plus pembrolizumab in patients with unresectable or metastatic melanoma (ECHO-301/KEYNOTE-252): a phase 3, randomised, double-blind study
Authors: Georgina V Long, Reinhard Dummer, Omid Hamid, Thomas F Gajewski, Christian Caglevic, Stephane Dalle, Ana Arance, Matteo S Carlino, Jean-Jacques Grob, Tae Min Kim, Lev Demidov, Caroline Robert, James Larkin, James R Anderson, Janet Maleski, Mark Jones, Scott J Diede, Tara C Mitchell
Journal: The Lancet Oncology (2019)
Topical sustained drug delivery to the retina with a drug-eluting contact lens
Authors: Amy E. Ross, Lokendrakumar C. Bengani, Rehka Tulsan, Daniel E. Maidana, Borja Salvador-Culla, Hidenaga Kobashi, Paraskevi E. Kolovou, Hualei Zhai, Koli Taghizadeh, Liangju Kuang, Manisha Mehta, Demetrios G. Vavvas, Daniel S. Kohane, Joseph B. Ciolino
Journal: Biomaterials (2019)
Improvement of diagnostic confidence and management of equivocal skin lesions by integration of reflectance confocal microscopy in daily practice: Prospective study in 2 referral skin cancer centers
Authors: Oriol Yélamos, Elena Manubens, Manu Jain, Marion Chavez-Bourgeois, Sri V. Pulijal, Stephen W. Dusza, Michael A. Marchetti, Alicia Barreiro, Maria L. Marino, Josep Malvehy, Miguel A. Cordova, Anthony M. Rossi, Milind Rajadhyaksha, Allan C. Halpern, Susana Puig, Ashfaq A. Marghoob, Cristina Carrera
Journal: Journal of the American Academy of Dermatology (2019)
Clinical Impact of Genomic Diversity From Early to Advanced Hepatocellular Carcinoma
Authors: Jean‐Charles Nault, Yoann Martin, Stefano Caruso, Théo Z. Hirsch, Quentin Bayard, Julien Calderaro, Cecile Charpy, Christiane Copie‐Bergman, Marianne Ziol, Paulette Bioulac‐Sage, Gabrielle Couchy, Jean‐Frédéric Blanc, Pierre Nahon, Giuliana Amaddeo, Nathalie Ganne‐Carrie, Guillaume Morcrette, Laurence Chiche, Christophe Duvoux, Sandrine Faivre, Alexis Laurent, Sandrine Imbeaud, Sandra Rebouissou, Josep M. Llovet, Olivier Seror, Eric Letouzé, Jessica Zucman‐Rossi
Journal: Hepatology (2019)

To date, genomic analyses of hepatocellular carcinoma (HCC) have been limited to early stages obtained from liver resection. We aim to describe the genomic profiling of HCC from early to advanced stages. We analyzed 801 HCC from 720 patients (410 resections, 137 transplantations, 122 percutaneous ablations, and 52 noncurative) for 190 gene expressions and for 31 gene mutations. Forty-one advanced HCC and 156 whole exome of Barcelona Clinic Liver Cancer (BCLC) 0/A were analyzed by whole-exome sequencing. Genomic profiling was correlated with tumor stages, clinical features, and survival. Our cohort included patients classified in BCLC stage 0 (9.4%), A (59.5%), B (16.2%), and C (14.9%). Among the overall 801 HCC, the most frequently mutated genes were telomerase reverse transcriptase (TERT) (58.1%), catenin beta 1 (CTNNB1) (30.7%), tumor protein 53 (TP53; 18.7%), AT-rich interaction domain 1A (ARID1A) (13%), albumin (11.4%), apolipoprotein B (APOB) (9.4%), and AXIN1 (9.2%). Advanced-stage HCC (BCLC B/C) showed higher frequencies of splicing factor 3b subunit 1 (SF3B1) (P = 0.0003), TP53 (P = 0.0006), and RB Transcriptional Corepressor 1 mutations (P = 0.03). G1-G6 transcriptomic classification and the molecular prognostic 5-gene score showed different distributions according to the stage of the disease and the type of treatment with an enrichment of G3 (P < 0.0001), poor prognostic score (P < 0.0001), and increased proliferation and dedifferentiation at the transcriptomic level in advanced HCC. The 5-gene score predicted survival in patients treated by resection (P < 0.0001) and ablation (P = 0.01) and in advanced HCC (P = 0.04). Twenty-two percent of advanced HCC harbored potentially druggable genetic alterations, and MET amplification was associated with complete tumor response in patients with advanced HCC treated by a specific MET inhibitor. Conclusion: Genomic analysis across the different stages of HCC revealed the mechanisms of tumor progression and helped to identify biomarkers of response to targeted therapies.
OP0349 NEURAL NETWORKS FOR AUTOMATED SCORING OF JOINT DISEASE ACTIVITY ON DOPPLER ULTRASOUND IMAGES
Authors: Jakob K. H. Andersen, Jannik S. Pedersen, Martin S. Laursen, Kathrine Holtz, Jakob Grauslund, Thiusius Rajeeth Savarimuthu, Søren Andreas Just
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> The development of standardized methods for ultrasound (US) scanning and evaluation of synovitis activity by the OMERACT-EULAR Synovitis Scoring (OESS) system, is a major step forward in the use of US in the diagnosis and monitoring of patients with inflammatory arthritis. The variation in interpretation of disease activity on US images can affect diagnosis, treatment and outcomes in clinical trials. <h3>Objectives</h3> To investigate if we could utilize neural network architecture for the interpretation of disease activity on Doppler US images, using the OESS scoring system. <h3>Methods</h3> Two state-of-the-art neural networks were used to extract information from 1342 Doppler US images from Rheumatoid Arthritis (RA) patients. One neural network that divided images as either healthy (Doppler OESS score 0 or 1) or diseased (Doppler OESS score 2 or 3). The other to score images across all four of the OESS systems Doppler US scores (0-3). The neural networks were hereafter tested on a new set of RA Doppler US images (n=176). Agreement between rheumatologist's scores and network scores was measured with the kappa statistic. <h3>Results</h3> For the neural network assessing healthy/diseased score, the highest accuracies compared to an expert rheumatologist were 86.4% and 86.9% with a sensitivity of 0.864 and 0.875 and specificity of 0.864 and 0.864, respectively. The other neural network developed to four class Doppler OESS scoring achieved an average per class accuracy of 75.0%, and a quadratically weighted kappa score of 0.84. <h3>Conclusion</h3> This study is the first to show that neural network technology can be used in the scoring of disease activity on Doppler US images according to the OESS system. <h3><b>Disclosure of Interests</b></h3> None declared
PB2076 MOLECULAR CYTOGENETIC ANALYSIS OF CHROMOSOME 7 ABERRATIONS IN MYELOID DISEASES
Authors: S. Ransdorfova, M. Onderkova, J. Brezinova, I. Sarova, M. Valerianova, K. Svobodova, H. Lhotska, L. Pavlistova, L. Lizcova, K. Michalova, Z. Zemanova, A. Jonasova, T. Stopka, J. Cermak
Journal: HemaSphere (2019)

Background: Complete or partial loss of chromosome 7 is a recurrent chromosomal aberration frequently found in myeloid disorders such as myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). This finding is an important prognostic indicator associated with poor response to the treatment and faster disease progression. Aims: (1) to determine the breakpoints on the long and short arm of chromosome 7 using FISH with locus‐specific probes; (2) to specify the frequency of these rearrangement; and (3) to evaluate overall survival [OS] of patients with chromosome 7 alteration. Methods: Diagnostic bone‐marrow samples of 46 adults with AML/MDS and with chromosome 7 aberration were examined. Karyotypes were analyzed using conventional and molecular cytogenetic techniques: FISH (Abbott, Kreatech), mFISH/mBAND (MetaSystems) and array CGH/SNP (Illumina, Agilent). Results: Monosomy 7 as a sole chromosomal abnormality was found in seven patients. Isolated deletion 7q was proved in one case only. In 38 cases, chromosome 7 aberrations were detected in combination with other changes (n = 16) or as a part of complex karyotype (n = 22). The most frequently altered regions on the long arm were identified in bands 7q22, 7q31 and 7q33‐7q36. In 17 patients (37%), deletion of the EZH2 tumor suppressor gene located in band 7q36.1 was found. The most frequently altered regions on the short arm were identified in bands 7p11‐p12. Rearrangements of 7p were always associated with other chromosomal alterations, the isolated 7p aberration was not proved. In 14 patients (30%), structural aberrations of both short and long arm 7p/7q were detected. In two cases, acquisition of additional clonal aberrations was observed during the disease. OS of the whole group was 6.45 months. Summary/Conclusion: In our cohort, the rearrangement of 7p as a sole aberration was not observed. A large heterogeneity of breakpoints was confirmed on the long arm 7q. High instability of chromosome 7 together with other chromosomal changes represent a marker of poor prognosis and is associated with rapid disease progression. In patients with myeloid malignancies, early detection of 7p/7q aberrations is important to precise prognostication and treatment decision. Supported by MH CZ‐DRO (IHBT, 00023736), RVO‐VFN64165, GACR P302/12/G157, Progres Q28/LF1.