tbuckley/cabot-search huggingface dataset:
Abstract P052: Glucometabolic State Transitions: The Jackson Heart Study
Authors: Alain G Bertoni, Haiying Chen, Valery S Effoe, Adolfo Correa, Mercedes Carnethon, Rita R Kalyani, Justin B Echouffo-Tcheugui, Joshua J Joseph, Joshua J Joseph, Sherita H Golden
Journal: Circulation (2016)

Background: To assess the frequency and determinants of transitions between normal fasting glucose (NFG), prediabetes and diabetes in an African American cohort. Methods: We included participants from the Jackson Heart Study who attended the baseline exam (2000-2004) and at least one of two subsequent exams (2005-2008 and 2009-2013), and were not missing data (fasting glucose, hemoglobin A1c, diabetes medication) used classify the glycemic status of participants as NFG, prediabetes, and diabetes at each visit. Transitions were defined as progression (deterioration) or remission (improvement) of glycemic status. Two transitions were possible for those attending all 3 visits. A generalized multinomial logit model, accounting for repeated measures from individuals with 2 transitions as clusters, was used to estimate the odds ratios (OR) for remission versus stable and progression versus stable, adjusting for demographic, anthropometric, behavioral, and biochemical factors. Results: Among 3,316 participants (baseline mean age 55 years, 36% male, 32% with IFG, 24% with diabetes) with data on at least one consecutive transition, 58.5% remained in their baseline status, 32.5% experienced a progression, 3.0% a remission, and 6.1% both a remission and progression. Among those classified as NFG, prediabetes, and diabetes at baseline: 1) progression occurred among 59%, 39%, and 2%; and 2) remission occurred among 7%, 13%, and 7%, respectively. The average weight change between exams was +1.4 kg for those experiencing only a progression and -4.5 kg for those with only a remission. Subsequent analyses included 2171 with complete data for all covariates which included baseline age, sex, education, BMI, smoking, alcohol use, hypertension medication, systolic blood pressure, log(triglycerides), baseline diabetes status, change in weight and change in log(CRP) between visits. The outcome of remission was associated only with weight change. A 1 kg increment in weight change was associated with a reduced likelihood of remission (OR 0.97, 95%CI: 0.96 - 0.99, p&lt;0.001). The outcome of progression was associated with baseline BMI, log(triglycerides), diabetes status, and weight change (OR for 1 kg increment weight change 1.04, 95%CI: 1.03 - 1.06, p&lt;0.001). Conclusions: In a contemporary adult African American population, transitions between glucometabolic statuses were frequent and most commonly involved deterioration. Weight changes between examinations were strongly associated with both remission and progression.
AB0144 EFFECTS OF AB501 (CERTOLIZUMAB MICE EQUIVALENT) IN ARTHRITIS INDUCED BONE LOSS
Authors: Bruno Vidal, Mikko A. Finnilä, Inês Lopes, Rita Cascão, Joao Eurico Fonseca
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Rheumatoid arthritis (RA) is a chronic immune-mediated inflammatory disease, which causes local and systemic bone damage. <h3>Objectives:</h3> The main goal of this work was to analyze, how treatment intervention with Ab501 (certolizumab mice equivalent) prevents the disturbances on bone structure and mechanics induced by arthritis. <h3>Methods:</h3> Thirty one DBA/1 collagen-induced arthritis (CIA) mice were randomly housed in experimental groups, as follows: arthritic untreated (N=10), preventive intervention with ab501 2 days before arthritis induction (N=10) and treatment intervention upon arthritis onset with ab501 (N=11). A non-induced group (N=5) was used as a control. Mice were monitored during 70 days after disease induction for the inflammatory score, ankle perimeter and body weight. Non-induced mice were used as controls. After 70 days of disease progression mice were sacrificed and bone samples were collected for histology, micro-computed tomography (μCT) and 3-point bending analysis. In addition, blood samples were also collected for bone turnover markers quantification. Statistical differences were determined with Mann–Whitney tests using GraphPad Prism (GraphPad, California, USA). Data were expressed as median with interquartile range. Differences were considered statistically significant for p&lt;0.05. <h3>Results:</h3> Results showed that Ab501 administration was able to control and abrogate disease development both in preventive and early therapeutic intervention. μCT results revealed that ab501 was able to preserve bone structure when delivered before arthritis induction. <h3>Conclusion:</h3> Ab501 preventive administration was able to control inflammation and prevent the degradative effects of arthritis on trabecular bone structure. <h3>Acknowledgement:</h3> This work was supported by UCB in the context of an Investigator Initiated Study where UCB provided financial and product support. <h3>Disclosure of Interests:</h3> Bruno Vidal Grant/research support from: Aspire Pfizer 2013, Mikko A. Finnilä: None declared, Inês Lopes: None declared, Rita Cascão: None declared, Joao Eurico Fonseca: None declared
PB1857 THE ROLE OF WHOLE‐BODY MAGNETIC RESONANCE IMAGING IN THE DETECTION OF VASCULAR EVENTS IN PATIENTS WITH PAROXYSMAL NOCTURNAL HEMOGLOBINURIA.
Authors: B. Navarro‐Almenzar, E. Salido Fiérrez, V. Cabañas Perianes, R. Pérez López, F. García Candel, E. Fernández Poveda, M. Blanquer Blanquer, J.D. Leal Rubio, B. Torregrosa Salas, J.M. Moraleda Jiménez
Journal: HemaSphere (2019)

Background: Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired clonal disorder characterized by intravascular hemolysis, cytopenias, and recurrent thrombosis. Thrombotic events are just the main cause of morbidity and mortality. Therefore, it is essential to detect them early to treat them and avoid sequels. Aims: To analyze the diagnostic value of the whole‐body magnetic resonance imaging (WB‐MRI) in the detection of symptomatic and silent vascular events. Methods: Retrospective study in which a 1.5 Tesla whole‐body magnetic resonance (Philips Achieva, Philips Medical Systems, Best, the Netherlands) with Gadolinium contrast was performed along 2017 and 2018 to patients diagnosed of classical PNH in Autonomous Community of the Region of Murcia, Spain. The image findings were analyzed. Four patients were included (3 men and 1 woman) with median age of 54 years, diagnosed of either PNH (n = 2) and AA/PNH (n = 2). At the time of investigation, mean size clon in granulocytes measured by FLAER was high (90.7 %, range 75.6‐99.3 %) and mean LDH was 341.7 U/L (range 204‐465 U/L; normal range 135‐214 U/L). Only one patient had prior history of thrombosis (Budd‐Chiari syndrome). All patients were treated according to Spanish PNH guidelines, including the use of complement inhibitor Eculizumab. Results: WB‐MRI findings showed unknown bone infarctions in two (50%) patients (patient 1 and patient 3). In patient 1, symptomatic bone infarctions was diagnosed (both femoral condyle and proximal tibias). Patient 3 showed an asymptomatic area of bone edema in distal left radial bone. Summary/Conclusion: Although the sample from our study is very small, it seems that WB‐MRI could be useful to evaluate vascular events, like bone infarctions, even subclinical ones. Our findings are consistent with the only article published to date ( Alaskar et al. Sci Rep. 2018; 8: 13458 ). Further studies are needed to test the effectiveness of WB‐MRI in the detection of vascular events and their relationship as a thrombotic event in PNH. image image
S1603 FIRST CLINICAL (PHASE 1B/2A) STUDY OF IBERDOMIDE (CC‐220; IBER), A CELMOD, IN COMBINATION WITH DEXAMETHASONE IN PATIENTS WITH RELAPSED/REFRACTORY MULTIPLE MYELOMA
Authors: S. Lonial, N.W. van de Donk, R. Popat, J.A. Zonder, M.C. Minnema, J.T. Larsen, T.V. Nguyen, M.S. Chen, A. Bensmaine, T. Biyukov, P. Sonneveld
Journal: HemaSphere (2019)

Background: IBER is a novel cereblon E3 ligase modulator (CELMoD) with enhanced tumoricidal and immunostimulatory activities. Preclinically, IBER overcomes immunomodulatory drug (IMiD) resistance and has synergy with daratumumab (DARA), bortezomib (BORT), and dexamethasone (DEX). Aims: This phase 1b/2a multicenter, open‐label, dose‐escalation study (NCT02773030) was conducted to evaluate the maximum tolerated dose (MTD), recommended phase 2 dose (RP2D), safety and preliminary efficacy of IBER in combination with DEX, in patients with relapsed/refractory multiple myeloma (RRMM). Methods: Eligible patients had RRMM and must have received ≥2 prior regimens including lenalidomide (LEN) and/or pomalidomide (POM), and a proteasome inhibitor (PI). All patients had progressed on or within 60 days of last MM therapy. Escalating doses of IBER were given on days 1–21, in combination with DEX 40 mg (20 mg in patients aged &gt;75 years) on days 1, 8, 15, and 22, of each 28‐day cycle. Dose escalation was reviewed by a dose escalation committee. Results: As of January 2019, 58 patients had received IBER + DEX. Median age was 64.5 years (range 33–79), and median number of prior regimens was 5 (2–12). Prior therapies included autologous stem cell transplantation (79%), LEN (100%), POM (69%), PIs (100%), and DARA (66%). IBER dose ranged from 0.3 to 1.2 mg; MTD/RP2D was not reached. Median duration of therapy was 12+ weeks (range 4–109). Grade 3–4 adverse events (AEs) were reported in 41 (72%) patients and were not related to dose. Grade 3–4 neutropenia, thrombocytopenia, neuropathy, and fatigue occurred in 26%, 11%, 2%, and 0% patients, respectively. Three patients discontinued treatment due to AEs. Clinical activity occurred early and was observed across all dose levels (Table 1); 20 of 51 patients remain on treatment (2–27+ cycles). Summary/Conclusion: IBER + DEX showed favorable efficacy and safety in heavily pretreated patients with RRMM who failed multiple prior therapies. This study is ongoing, including combinations of IBER with DARA or BORT. image
Abstract 20262: Hidden Lesion is Associated With Poor Prognosis in Patients With Acute Chest Pain Without Significant Coronary Stenosis
Authors: Akira Taruya, Atsushi Tanaka, Manabu Kashiwagi, Takashi Kubo, Takeshi Hozumi, Takashi Akasaka
Journal: Circulation (2017)

Introductions: It has been widely recognized that acute coronary syndrome develops from plaque disruption followed by obstructive thrombus formation. Sometimes, on the other hand, non-obstructive c...
AB0526 PRIMARY SJOGREN’S SYNDROME AND ORGAN SYSTEM INVOLVEMENT: A RETROSPECTIVE STUDY OF 153 PATIENTS FROM WESTERN INDIA
Authors: Girish Kakade, Piyush Joshi, Canchi Balakrishnan, Akash Khune
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Primary Sjogren's syndrome (pSS) is under diagnosed and improperly treated disease because of its variable modes of presentation. Limited data is available on pSS from India. <h3>Objectives:</h3> To describe organ system involvement in patients with pSS and compare to other studies. <h3>Methods:</h3> Retrospective proforma based analysis of patients with pSS (AECG 2002 criteria) from 2002-2012 at a tertiary rheumatology centre was done. Demographic data and systemic organ involvement of patients was noted. <h3>Results:</h3> We had 153 consecutive patients of pSS (135 females, 18 males) in the 10 years which were included. Mean age at diagnosis was 47±11.62 years. Mean duration of sicca symptoms was 32 (±31) months prior to presentation. Organ system involvement was seen in 93 (60.7%) patients as follows:- Musculoskeletal involvement in 90 (58.8%) patients, Skin involvement in 48 (31%) patients, Lung involvement in 27 (17.6%) patients, Renal involvement in 22 (14.3%) patients, Neurological involvement in 21 (13.7%) patients, GI involvement in 6 (3.9%) patients and Lymphoma in 2 (1.3%) patients. Comparison of organ system involvement with other major studies of pSS is shown in table 1. <h3>Conclusion:</h3> Indian pSS patients are younger than their European counterparts. Majority of these patients show organ system involvement. Raynaud's phenomenon is rare in Indian patients. Lung, renal and gastrointestinal involvement in Indian patients is more prevalent than in European patients, but less prevalent than in Chinese patients. Musculoskeletal and neurological involvement is similar across different populations. <h3>References</h3> [1] Ramos-Casals M, Solans R, Rosas J, et al. GEMESS Study Group. Primary Sjogren syndrome in Spain: clinical and immunologic expression in 1010 patients. Medicine (Baltimore) 2008; 87: 210-9. [2] Sandhya P, Jeyaseelan L, Scofield RH, Danda D. Clinical Characteristics and Outcome of Primary Sjogren's Syndrome: A Large Asian Indian Cohort. The Open Rheumatology Journal. 2015;9:36-45. <h3>Disclosure of Interests:</h3> None declared
PB2044 DIAGNOSIS OF IRON DEFICIENCY ANAEMIA AND PARENTERAL IRON THERAPY: CLINICAL AUDIT IN A DISTRICT GENERAL HOSPITAL
Authors: S. Lovato, H. Ali, B. Dahotia, B. Bhatkal
Journal: HemaSphere (2019)

Background: Iron deficiency anaemia is the most common cause of anaemia. Parenteral iron therapy in the UK has to be administered in hospital settings as it comes with risk of allergic reactions and anaphylaxis. Clear procedures should be established in each hospital to ensure that parenteral iron therapy is prescribed according to the national guidelines ans audited regularly. Aims: The aim of this audit was to estabilish if if the diagnosis of iron deficiency was performed according to the guidelines and if patients were adequately monitored after receiving parenteral iron. Methods: Pharmacy provided the list of IV iron prescriptions issued in a period of 12 months. A clinical audit was performed to understand if patients had a documented diagnosis of iron deficiency (low haemoglobin, low ferritin or low transferrin saturation according to the local laboratory ranges); if there was a follow up blood test including the same parameters and if patients who were still iron deficient were prescribed further iron. Results: A total of 233 prescription for 227 patients were analysed. Of those 99% had a blood test previous to the iron infusion (99% had full blood count, 94% had ferritin level, 63% had transferrin saturation). Only 80% of patients had confirmed iron deficiency, in 2 % of the patients there was no iron deficiency and in 1 patient there were laboratory signs of iron overload, in the remaining 18% iron status was incomplete as transferrin saturation was not performed. Follow up was missing in 16% of the cases, in 66% of the patients was done between 2 weeks and three monts, in 20% of the cases after that. All the patients had full blood count, only two thirds had ferritin level done and less than a quarter had transferrin level done. Thirty nine patients (17% o) were found to be still iron deficient but only a fifth of them received further iron therapy. Only 10% had normal iron studies, in the remaining cases iron status was not evaluable. Summary/Conclusion: Several issues were identified that will require improvement. First of all we found that some of the prescriptions were unnecessary (2%) or controindicated (0.5%). In a fifth of the cases as iron studies were incomplete, was not possible to establish of the therapy given was appropriate. The main problem was lack of follow up or follow up with incomplete iron studies that made impossible to interpret the iron status in tre quarter of the patients, and missed iron therapy in five out of six patient with documented iron deficiency. Resolving these problem, as they are not isolated to a single department, will be a challenge. Solutions should be found to ensure that there are no inappropriate parenteral iron prescriptions and that patients are monitored adequately and given further therapy when required. Establishing an iron deficiency service to monitor patients could be one of these solutions, but it will require major institution re‐organisation. image
Selective Constraints on Coding Sequences of Nervous System Genes Are a Major Determinant of Duplicate Gene Retention in Vertebrates
Authors: Julien Roux, Jialin Liu, Marc Robinson-Rechavi
Journal: Molecular Biology and Evolution (2017)

The evolutionary history of vertebrates is marked by three ancient whole-genome duplications: two successive rounds in the ancestor of vertebrates, and a third one specific to teleost fishes. Biased loss of most duplicates enriched the genome for specific genes, such as slow evolving genes, but this selective retention process is not well understood. To understand what drives the long-term preservation of duplicate genes, we characterized duplicated genes in terms of their expression patterns. We used a new method of expression enrichment analysis, TopAnat, applied to in situ hybridization data from thousands of genes from zebrafish and mouse. We showed that the presence of expression in the nervous system is a good predictor of a higher rate of retention of duplicate genes after whole-genome duplication. Further analyses suggest that purifying selection against the toxic effects of misfolded or misinteracting proteins, which is particularly strong in nonrenewing neural tissues, likely constrains the evolution of coding sequences of nervous system genes, leading indirectly to the preservation of duplicate genes after whole-genome duplication. Whole-genome duplications thus greatly contributed to the expansion of the toolkit of genes available for the evolution of profound novelties of the nervous system at the base of the vertebrate radiation.
Novel Inter‐omic Analysis Reveals Relationships Between Diverse Gut Microbiota and Host Immune Dysregulation in HLA–B27–Induced Experimental Spondyloarthritis
Authors: Tejpal Gill, Stephen R. Brooks, James T. Rosenbaum, Mark Asquith, Robert A. Colbert
Journal: Arthritis & Rheumatology (2019)

Objective To define inflammation‐related host–microbe interactions in experimental spondyloarthritis (SpA) using novel inter‐omic approaches. Methods The relative frequency of gut microbes was determined by 16S ribosomal RNA (rRNA) gene sequencing, and gene expression using RNA‐Seq of host tissue. HLA–B27/human β 2 ‐microglobulin–transgenic (HLA–B27–transgenic) and wild‐type rats from dark agouti, Lewis, and Fischer backgrounds were used. Inter‐omic analyses using Cytoscape were employed to identify relevant relationships. PICRUSt was used to predict microbial functions based on known metagenomic profiles. Results Inter‐omic analysis revealed several gut microbes that were strongly associated with dysregulated cytokines driving inflammatory response pathways, such as interleukin‐17 (IL‐17), IL‐23, IL‐17, IL‐1, interferon‐γ (IFNγ), and tumor necrosis factor (TNF). Many microbes were uniquely associated with inflammation in Lewis or Fischer rats, and one was relevant on both backgrounds. Several microbes that were strongly correlated with immune dysregulation were not differentially abundant in HLA–B27–transgenic compared to wild‐type controls. A multi‐omic network analysis revealed non‐overlapping clusters of microbes in Lewis and Fischer rats that were strongly linked to overlapping dysregulated immune/inflammatory genes. Prevotella , Clostridiales , and Blautia were important in Lewis rats, while Akkermansia muciniphila and members of the Lachnospiraceae family dominated in Fischer rats. Inflammation‐associated metabolic pathway perturbation (e.g., butanoate, propanoate, lipopolysaccharide, and steroid biosynthesis) was also predicted from both backgrounds. Conclusion Inter‐omic and network analysis of gut microbes and the host immune response in experimental SpA provides an unprecedented view of organisms strongly linked to dysregulated IL‐23, IL‐17, IL‐1, IFNγ, and TNF. Functional similarities between these organisms may explain why animals of different genetic backgrounds exhibit common patterns of immune dysregulation, possibly through perturbation of similar metabolic pathways. These results highlight the power of linking analyses of gut microbiota with the host immune response to gain insights into the role of dysbiotic microbes in SpA beyond taxonomic profiling.
Comparison of the accuracy of human readers versus machine-learning algorithms for pigmented skin lesion classification: an open, web-based, international, diagnostic study
Authors: Philipp Tschandl, Noel Codella, Bengü Nisa Akay, Giuseppe Argenziano, Ralph P Braun, Horacio Cabo, David Gutman, Allan Halpern, Brian Helba, Rainer Hofmann-Wellenhof, Aimilios Lallas, Jan Lapins, Caterina Longo, Josep Malvehy, Michael A Marchetti, Ashfaq Marghoob, Scott Menzies, Amanda Oakley, John Paoli, Susana Puig, Christoph Rinner, Cliff Rosendahl, Alon Scope, Christoph Sinz, H Peter Soyer, Luc Thomas, Iris Zalaudek, Harald Kittler
Journal: The Lancet Oncology (2019)
Effect of fertility concerns on tamoxifen use in young survivors of breast cancer.
Authors: Natalia Llarena, Omar Nunez, Anna Kane, Jacqueline Sara Jeruss
Journal: Journal of Clinical Oncology (2013)

572 Background: For premenopausal patients with ER+ breast cancer, a 5-year course of tamoxifen results in a 47% reduction in annual recurrence risk and a 26% reduction in annual mortality. Despite these benefits, adherence rates for tamoxifen are low, particularly among younger women. We hypothesize that fertility concerns are causally related to the poor tamoxifen adherence rates observed among young breast cancer survivors. Methods: With IRB approval, a retrospective analysis of 535 women with breast cancer between 2000-2012 was undertaken. Patients were younger than age 46, premenopausal and had ER+ breast cancer. 138 patients did not complete a 5-year course. Patient and provider factors that influenced tamoxifen initiation and adherence were reviewed: (1) evidence of referral to a fertility specialist; (2) documentation of discussion about tamoxifen-related fertility concerns; (3) agreement to take tamoxifen; (4) duration of tamoxifen use. Phone interviews conducted with 27 patients focused on lack of initiation or early discontinuation. The Log-rank (Mantel-Cox) test was used to compare Kaplan-Meier curves and generate hazard ratios. Results: Of the 138 patients who did not complete 5 years of therapy, 38 (27.5%) failed to initiate or discontinued tamoxifen secondary to fertility concerns. Only 114 (21.3%) charts documented referral to a fertility specialist. Patients who expressed a desire to maintain fertility or to have children in the future (115 patients, 21.5%) were more likely to discontinue tamoxifen treatment (HR=2.7, p=0.001). Other critical factors included being unmarried (HR=1.9, p=0.011) and lack of college education (HR=2.5, p=0.0008). Major themes from phone interviews: (1) patients felt they were not adequately informed about fertility preservation and had to pursue information independently; (2) patients did not initiate/resume tamoxifen postpartum because of inadequate physician guidance. Conclusions: Concerns about fertility have a significant negative impact on the initiation and adherence to tamoxifen for young breast cancer patients. Efforts to improve tamoxifen adherence among young cancer patients should include prioritization of fertility preservation as part of the treatment plan.