tbuckley/cabot-search huggingface dataset:
AB1340 IMPACT OF THERAPEUTIC PATIENT EDUCATION ON THE SAFETY OF PATIENTS ON BIOTHERAPY FOR CHRONIC INFLAMMATORY RHEUMATISM
Authors: BENCHARIF IMEN, Dalila Bendjenna
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Patients treated with biotherapy should be aware of the specific complications. The acquisition of safety skills is one of the objectives of therapeutic patient education programs in chronic inflammatory rheumatism.(1,2,4) <h3>Objectives:</h3> Evaluation of the impact of the "EST-RIC" therapeutic patient education program on the safety skills of patients on biotherapy for chronic inflammatory rheumatism. <h3>Methods:</h3> Descriptive cross-sectional study evaluating the impact of integration into a therapeutic patient education program on the skills of patients treated in a day hospital at the Constantine rheumatology department for chronic inflammatory rheumatism, using the validated "BioSecure" questionnaire (3) <h3>Results:</h3> Of sixty patients, fifty-two patients (86.6%) completed the questionnaire. Forty-three patients have spondyloarthritis (83%) <b>(Tab1)</b> The median Biosecure score was 62.90/100 (SD 10.83). Fifty-two percent of the patients had integrated the therapeutic education program. Their Biosecure score was significantly higher than that of naïve patients with therapeutic education (median score 69/100 in the ETP group versus 58/100, p &lt;0.001) <b>(Fig 1).</b> The Bioscure score varied significantly with the lower level of education (p &lt;0.0001), in the subgroup of patients with a professional activity (P = 0.008) and in patients whose treatment was introduced for less than one year (p &lt;0.0001) and who had a pathology whose diagnosis was less than 5 years (p &lt;0.008) <h3>Conclusion:</h3> The integration of patients undergoing biotherapy into a specialized program of therapeutic patient education is correlated with a better mastery of theoretical safety skills. <h3>References</h3> [1] Orefice D, Beauvais C, Gossec L, et al. Cross-sectional study of self-care safety skills in 677 patients on biodrugs for inflammatory joint disease. Joint BoneSpine Rev Rhum 2014;81:502–7. [2] Claudepierre P, Flipo R-M, Sibilia J, et al. Patient's knowledge of their disease: a multicenter study in ankylosing spondylitis. Bone Spine2004; 71: 550-6. [3] Gossec L, Fautrel B, Flipon E, et al. Tolerance of biotherapies: development and validation of a questionnaire evaluating self-management and patient safety skills: the Biosecure questionnaire. An initiative of the French Rheumatology Society, Therapeutic Education Section. Rev Rhum2013; 80: 479-85. [4] Meesters JJL, Vliet Vlieland TPM, Hill J, et al. Measuring educational needsamong patients with rheumatoid arthritis using the Dutch version of the Needs Assessment Tool (DENAT). Clin Rheumatol2009; 28: 1073-7. <h3>Disclosure of Interests:</h3> None declared
Abstract 21198: Human Atrial Natriuretic Peptide Levels in Combination With Plasma Brain Natriuretic Peptide Levels Predict Cardiac Function in Patients With Light-Chain Amyloidosis
Authors: Jun Koyama, Kouichirou Kuwahara
Journal: Circulation (2017)

Introduction: Plasma brain natriuretic peptide (BNP) levels are known to be a predictor of cardiac dysfunction in patients with systemic light-chain amyloidosis (AL). There is no data about the clinical significance of human atrial natriuretic peptide (h-ANP) levels in combination with BNP. Hypothesis: Plasma h-ANP levels in combination with plasma BNP levels provide additional information about the cardiac function in patients with AL. Methods: We prospectively examined 100 consecutive, untreated patients with biopsy-proven systemic AL amyloidosis with data of BNP and h-ANP. Patients were divided into 4 groups by h-ANP (median value, 29pg/mL) and BNP (median value, 68pg/mL) levels. We assessed diastolic wall strain (DWS) calculated from M-mode in left ventricular (LV) posterior wall (PW) as the following equation {(LVPWs - LVPWd)/LVPWs} (s, at end-systole; d, at end-diastole), standard 2-dimensional echocardiography, Doppler flow measurements, and LV global longitudinal strain (GLS) by speckle tracking echocardiography. Plasma levels of h-ANP and BNP were measured on the day of echocardiography. Results: In the group with both higher level of h-ANP and BNP, the DWS was significantly lower than the other 3 groups. This group showed significantly higher values in the ratio of trans-mitral early to late diastolic flow velocity, the ratio of pulmonary venous diastolic to systolic ratio, the septal E/e’, and GLS compared with the other 3 groups. Conclusions: Plasma h-ANP levels in combination with BNP levels provide useful information about cardiac function in patients with AL.
FRI0485 TIMED UP AND GO TEST FOR VERTEBRAL FRACTURE PREDICTION
Authors: Cyrine Daldoul, Nejla El Amri, Khadija Baccouch, Amine Kalai, Mohamed Amine Triki, Hela Zeglaoui, Elyes Bouajina
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Sarcopenia describes the age related loss of skeletal muscular mass and function. The development of sarcopenia may confer an increased risk of falls which leads to a potential increase in fracture. The Timed Up and Go (TUG) Test is one of clinical tools used to assess sarcopenia. <h3>Objectives</h3> We hypothesized that slow TUG test performance would predict vertebral fracture (VF) in post-menopausal women independently of bone mineral density (BMD) and other risk factors. <h3>Methods</h3> This is a cross sectional study enrolled from September 2018 to December 2018, including post-menopausal women referred to rheumatology department for measure of BMD. All subjects underwent dual energy X-ray absorptiometry (DeXA) and physical performance tests including the TUG test. TUG performance was considered low if it took, 15 seconds or longer. A vertebral fracture assessment (VFA) image was obtained which was subsequently scored for the presence of significant vertebral deformities. VF grade 1 were excluded. <h3>Results</h3> Eighty four patients were included. The mean age of our patients was 62.29±8.27 years with an average body mass index (BMI) of 31.45±6.21 kg/m<sup>2</sup> [18.18-44.38]. According to the WHO classification 42 patients (50%) had osteoporosis. Among 84 women, 47 had a low TUG performance. Subjects with low TUG performance had an older age (57.94 vs 65.71 years) (p&lt;0.001), and had a significantly lower BMD at femoral neck (0.825 g/cm<sup>3</sup>vs 0.752 g/cm<sup>3</sup>) (p&lt;0.001). There was no significant difference between the two groups regarding duration of menopause, history of previous fragility fracture, body mass index and BMD at total hip and at vertebral site. Osteoporosis was found in 30 patients who had low TUG performance and in 12 patients who had normal TUG performance without statistically significant difference (p=0.08).VF were assessed in 22 subjects. VF were found in 20 patients with low TUG performance (42.55%). Compared with the group with normal TUG performance, subjects with low TUG performance had significantly higher number of fracture (p&lt;0.001).A significant correlation was found between the number of VF and the score of get up and go test (Khi-2 test, p&lt;0.001). <h3>Conclusion</h3> Our study found a strong relationship between TUG performance and prevalent vertebral fracture. Therefore evaluation of additional risk factors may improve the prediction of vertebral fracture in post-menopausal women. <h3>Disclosure of Interests</h3> None declared
Low Awareness of Scammers’ Tactics Linked to Dementia Risk in Cognitively Normal People
Authors: Rita Rubin
Journal: JAMA (2019)

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PAGA: graph abstraction reconciles clustering with trajectory inference through a topology preserving map of single cells
Authors: F. Alexander Wolf, Fiona K. Hamey, Mireya Plass, Jordi Solana, Joakim S. Dahlin, Berthold Göttgens, Nikolaus Rajewsky, Lukas Simon, Fabian J. Theis
Journal: Genome biology (2019)

Single-cell RNA-seq quantifies biological heterogeneity across both discrete cell types and continuous cell transitions. Partition-based graph abstraction (PAGA) provides an interpretable graph-like map of the arising data manifold, based on estimating connectivity of manifold partitions ( https://github.com/theislab/paga ). PAGA maps preserve the global topology of data, allow analyzing data at different resolutions, and result in much higher computational efficiency of the typical exploratory data analysis workflow. We demonstrate the method by inferring structure-rich cell maps with consistent topology across four hematopoietic datasets, adult planaria and the zebrafish embryo and benchmark computational performance on one million neurons.
Total internal reflection-based single-vesicle in situ quantitative and stoichiometric analysis of tumor-derived exosomal microRNAs for diagnosis and treatment monitoring
Authors: Dinggeng He, Huizhen Wang, See-Lok Ho, Hei-Nga Chan, Luo Hai, Xiaoxiao He, Kemin Wang, Hung-Wing Li
Journal: Theranostics (2019)

Purpose: Exosomes (EXs) have been increasingly recognized as natural nanoscale vehicles for microRNA (miRNA)-based cell-cell communication and an ideal source of miRNA biomarkers in bodily fluids.Current methods allow bulk analysis of the miRNA contents of EXs, but these approaches are not suitable for the in situ stoichiometry of exosomal miRNAs and fail to reveal phenotypic heterogeneity at the single-vesicle level.This study aimed to develop a single vesicle-based, mild, precise, but versatile method for the in situ quantitative and stoichiometric analysis of exosomal miRNAs.Methods: A total internal reflection fluorescence (TIRF)-based single-vesicle imaging assay was developed for direct visualization and quantification of the single-vesicles of EXs and their miRNA contents in serum microsamples.The assay uses co-delivery of inactive split DNAzymes and fluorescence-quenched substrates into nanosized EXs treated with streptolysin O to produce a target miRNA-activated catalytic cleavage reaction that amplifies the readout of fluorescence signal.We perform the in situ quantitative and stoichiometric analysis of serum exosomal hsa-miRNA-21 (miR-21), a common cancer biomarker, by using the developed TIRF imaging assay. Results:The TIRF imaging assay for serum exosomal miR-21 can distinguish cancer patients from healthy subjects with better performance than conventional real-time polymerase chain reaction (PCR) assay.The exosomal miR-21 level in serum is also informative for monitoring tumor progression and responses to treatment.Moreover, the TIRF assays can readily determine the precise stoichiometry of target exosomal miRNA contents in situ by delivering molecular beacon (MB) probes into EXs.Conclusions: The created TIRF imaging platform shows high applicability to serve as a universal and useful tool for the single-vesicle in situ quantitative and stoichiometric analysis of other disease-associated exosomal miRNAs markers and provide valuable insight into the physiological relevance of EX-mediated miRNA communication.
Corrigendum to “Evolution of pancreatectomy with en bloc venous resection for pancreatic cancer in Italy. Retrospective cohort study on 425 cases in 10 pancreatic referral units” [Int. J. Surg. 55 (2018) 103–109]
Authors: Giuseppe Nigri, Niccolò Petrucciani, Antonio Daniele Pinna, Matteo Ravaioli, Elio Jovine, Francesco Minni, Gian Luca Grazi, Piero Chirletti, Gianpaolo Balzano, Fabio Ferla, Luciano De Carlis, Giuseppe Tisone, Niccolò Napoli, Ugo Boggi, Giovanni Ramacciato
Journal: International Journal of Surgery (2019)
S119 THE ROLE OF RECURRENT SOMATIC ALTERATIONS IN THE NON-CODING GENOME WITH FUNCTIONAL IMPLICATIONS IN MM
Authors: M. Samur, R. Szalat, A. Aktas Samur, M. Fulciniti, M. Lopez, M. Shammas, P. Richardson, F. Magrangeas, S. Minvielle, P. Moreau, M. Attal, A. Thakurta, K. Anderson, G. Parmigiani, H. Avet-Loiseau, N. Munshi
Journal: HemaSphere (2019)

Background: Multiple Myeloma (MM) is a heterogenous disease with distinct molecular and clinical characteristics. Recent large collaborative efforts have identified number of driver genes. However over 96% of all somatic alterations occur in non-coding regions and very little is known about how they affect the disease. Aims: Using our large dataset from uniformly treated newly diagnosed patinets as well as relpased patient samples, we investigated the somatic alterations in the non coding genome to identify critical hotspots. Methods: We performed a deep (average coverage > 80X) whole genome sequencing (WGS) on 376 MM samples (240 newly diagnosed, 52 first relapse and 84 rrMM) as well as RNAseq to comprehensively analyze recurrent somatic alterations in non-coding regions. Results: We detected median 9,649 (Range 3,194–126,935) mutations and indels per sample with overall more than 4 M total somatic mutations. Introns (> 2.5 mutations/per Mb) and intergenic regions (> 3 mutations/per Mb) had significantly higher number of mutations per megabase compared to Exons (∼2 mutations/per Mb) (p < 1e-5). Mutations in coding regions in our data was similar to published whole exome sequencing studies with increase in several driver mutations at relapse. We observed 57 [range 7 - 376] structural variants (SVs) per sample with > 98% involving non-coding regions. We identified 48 SV hotspots that are targeting tumor suppressor genes or key regulatory elements such as TCF3 and TNFSF10 and these SVs were also associated with significantly altered expression of the target genes. We have detected two less defined translocations targeting MAP3K14 and NFKB1 and driving the expressions of these genes. Our data showed that ∼80% of translocation breakpoints are in the close proximity of super enhancers and therefore Ig is not the only mechanism over expresses the target genes. We detected >500 single nucleotide hotspots in the con-coding genome some of which are targeting 5’UTR and introns of BCL7A, BCL6, CD93, CCND1, PAX5. Some of these hotspots were correlated with disease outcome. We also observed that overall mutational load is also associated with disease outcome. We detected chromothripsis in ∼25% of newly diagnosed samples; and kataegis hotspots on chromosome 3q27-3q28 (24%), 11q13 (5.8%) and 12q24 (5.3%). Summary/Conclusion: In conclusion, this large deep whole genome sequencing data from newly-diagnosed MM patients identifies a vast majority of non-coding mutations with potentially significant functional and biological role in MM. Our integrative approach using both WGS and RNA-seq data from the patients now provides us important tools to further characterize the impact of these mutations and develop opportunities for targeted therapeutics.
Implications of health status, health-related quality of life, and socioeconomic outcomes in childhood brain tumor survivors
Authors: F Daniel Armstrong
Journal: Neuro-Oncology (2019)

Children treated for tumors of the central nervous system (CNS) are known to be at risk for a number of neurocognitive late effects of the tumor and its treatment, most commonly neurocognitive function and school performance.Specific difficulties include processing speed, working memory, and executive function, which translate to school-related learning problems in reading and math.Poorer outcomes are strongly associated with: (1) whether cranial radiation therapy (CRT) is used, (2) the dose of CRT, (3) chemotherapy regimens alone or in combination with CRT, and (4) younger age at time of treatment.Children treated with neurosurgical tumor resection alone are also at risk for late effects, although at a lower level of severity. 1,2dult survivors of pediatric astrocytomas treated with CRT have reported a number of long-term global functional outcomes, including poorer mental health and general health, functional impairment, activity limitations, and lower rates of college graduation, marriage, employment, and household income. 3In this issue, Scholtes and colleagues 4 report on the health status, health-related quality of life, and socioeconomic status in a German cohort of World Health Organization (WHO) grades I-II brain tumor survivors (BTS) and WHO grades III-IV BTS.The cohort (N = 270) had all been diagnosed before age 15 with a posterior fossa tumor, were more than 5 years after completion of treatment, and were between 25 and 45 years of age at the time of survey.The WHO I-II BTS were primarily treated for astrocytoma (85%) and WHO III-IV BTS were primarily treated for medulloblastoma (84.7%).The groups were similar regarding age at diagnosis and follow-up, but treatment intensity (including CRT) was greater for the WHO III-IV BTS group.WHO grades I-II BTS were similar to the general population on measures of physical and social function, symptoms, and global health-related quality of life, but self-reported lower function on measures of role, emotional, and cognitive function and higher levels of fatigue, appetite loss, and financial difficulties.Educational attainment and employment rates Overall survival
PB1775 CYTARABINE-INDUCED NEUROTOXICITY WELL-RESPONDING TO METHYL PREDNISOLONE.
Authors: B. Balik Aydin
Journal: HemaSphere (2019)

Background: Cytarabine-induced neurotoxicity well-responding to methyl prednisolone Aims: Neurotoxicity is a well-recognized complication of high-dose cytosine arabinoside (HIDAC). We describe a patient with AML who suffered cerebellar toxicity following high-dose cytarabine and showed excellent response to methylprednisolone. Methods: A 34-year-old male with acute myeloid leukemia (AML) M1 presented with dysarthria in the inpatient clinic. He had been previously diagnosed with myeloblastic leukemia with maturation type AML, negative for t(8:21), t(9:22), CEBPA and FLT3-TKD mutations by PCR. Cytogenetics were 46, XY. Prior to her presentation, he was treated with induction chemotherapy, which consisted of cytarabine 200 mg/m2 on days 1–7, idarubicin 12 mg/m2 on days 1–3. After induction chemotherapy, he had complete morphologic and immunophenotypic remission of her leukemia on bone marrow biopsy, which was followed by one consolidation cycle of high-dose cytarabine (3 gm/m2 on days 1, 3 and 5). After the first cycle of consolidation therapy, on day six he began to complain of dysarthria, dizziness, gait disorder and balance loss. His cumulative dose of cytarabine at that time was 37.400 g. On physical exam, he had not be able to walk in a straight line, he had dysarthria but he had not dysmetria and dysdiadochokinesia. Gait was ataxic and the rest of neurologic examination was generally normal. MRI and CT of the brain showed no acute pathologic findings. His neurologic symptoms were presumed to be secondary to cytarabine neurotoxicity. He was started on prednisone 80 mg daily over 7 days with rapid resolution of his symptoms within a few days of starting corticosteroids. The steroids were tapered by halving the dose each 3 days over the following 2 weeks. The patient did not receive any additional consolidation treatments with cytarabine, though he remained on maintenance allogeneic hematopoietic cell transplantation (HCT), donor was his brother. He is currently doing well and remains in remission from his disease, without neurologic deficits. Results: An excellent response to methylprednisolone in our patient strongly suggests an immune mediated mechanism of neurotoxicity. The patient's improvement in symptoms may have been spontaneous or due to the steroid effect but suggests a possible treatment approach. Summary/Conclusion: There are no standardized treatments for cytarabine- induced neurotoxic effects, besides discontinuation of the drug. There are only a few cases in the literature.(1) We choice treatment with corticosteroids in this case. The patient presented with neurologic deficits soon after followed by rapid resolution of symptoms after initiation of corticosteroids. This case support the theory of an immune-mediated mechanism and will hopefully serve as a potential treatment for those experiencing neurotoxicity with cytarabine in the future
SAT0163 LOW CARDIOVASCULAR EVENT RATE DURING TOCILIZUMAB TREATMENT IN THE NON-INTERVENTIONAL STUDY ICHIBAN
Authors: Christof Specker, Annette Alberding, Martin Aringer, Gerd Rüdiger Burmester, Michael W. Hofmann, Peter Kästner, Herbert Kellner, Christina Luig, Frank Moosig, Maren Sieburg, Hans-Peter Tony, Gerhard Fliedner
Journal: Annals of the Rheumatic Diseases (2019)

Conclusion:A pooled analysis of TNF inhibitor biosimilars and reference products showed that about 20-30% of responders lost their response, while about 20-30% gained it.Thus, the overall stability of disease fluctuation in our 1-year phase III studies is a consequence of a similar success and failure rate.The validity of these data can be seen by the similarities in these outcomes between different types of TNF-inhibitors and similarity between biosimilars and respective reference products.