tbuckley/cabot-search huggingface dataset:
PB2317 CHOICE OF VENOUS ACCESS FOR CHRONIC RED CELL EXCHANGE IN CHILDREN WITH SICKLE CELL DISEASE
Authors: P. Velasco, G. Guillen, C. Diaz de Heredia, J. Fernandez
Journal: HemaSphere (2019)

Background: Among the options of chronic transfusion regimen in sickle cell anemia (SCA), red cell exchange (RCE) is the most efficient method. In pediatrics, permanent venous accesses minimize venous punctions and improve the quality of life. Port‐a‐cath (PAC) are the devices with the least infectious complications. The recommended size of the PAC is related to the patient's age and weight Patients with SCA have a higher risk of thrombotic complications. Aims: Our objective is to select the most versatile and small PACs, to reduce thrombotic risk, which allow adequate flows to perform RCE. Methods: Selection of PAC marketed in Europe with one and two lumen, depending on the size of the reservoir, catheter, speed and availability in Europe Ex vivo analysis of the maximum flows tolerated by the ”Spectra Optia“ machine during the RCE procedure, using expired red blood cell concentrates and Gripper needles of 19 and 20G. Implantation of the device and analysis of the efficacy of the procedure in 2 patients with SCA in a chronic transfusion regimen for 2 years Results: After a first screening, the Cardiva PHS Medical 10.5fr double‐lumen PACs were analyzed; Bard 9.5 fr and Vortex Angyodinamics 11.4 fr. As a PAC of single lumen, the Smart Port CT mini Angyodinamics of 6.6 fr was analyzed, in order to use an extraction PAC and a return one for the same vessel. The catheters that showed better results were those of Angyodinamics, using Gripper of 19G and reaching flows of 25‐30 ml / min. Among these PACs, we selected the 6.6 fr of single lumen for the following reasons: smaller reservoir (more suitable for small and thin children), separate devices that allow only one of them to be replaced if a light is obstructed and because a Single‐light PAC could be sufficient if in the future Spectra Optima allows the unipuncture mode. In vivo, we successfully implanted the 2 PAC of single lumen selected in 2 patients of more than 40 kg, in which we were able to perform RCE every 6 weeks, during the last 2 years. The procedure is performed in an average of 3 hours. There have been no complications of thrombosis, obstruction or infection to date. Summary/Conclusion: The exvivo test allowed to discard devices not suitable for the procedure and to select a single lumen PAC model of 6.6 fr that allows sufficient flows to perform the chronic RCE in pediatric patients of any age and weight, minimizing the associated infectious and thrombotic risks to permanent accesses in patients with ACF.
Toll-like receptor 3 downregulation is an escape mechanism from apoptosis during hepatocarcinogenesis
Authors: Marc Bonnin, Nadim Fares, Barbara Testoni, Yann Estornes, Kathrin Weber, Béatrice Vanbervliet, Lydie Lefrançois, Amandine Garcia, Alain Kfoury, Floriane Pez, Isabelle Coste, Pierre Saintigny, Alain Viari, Kévin Lang, Baptiste Guey, Valérie Hervieu, Brigitte Bancel, Birke Bartoch, David Durantel, Toufic Renno, Philippe Merle, Serge Lebecque
Journal: Journal of Hepatology (2019)
Comparison of Outcomes After Transcatheter Aortic Valve Replacement vs Surgical Aortic Valve Replacement Among Patients With Aortic Stenosis at Low Operative Risk
Authors: Marko P. O. Virtanen, Markku Eskola, Maina P. Jalava, Annastiina Husso, Teemu Laakso, Matti Niemelä, Tuomas Ahvenvaara, Tuomas Tauriainen, Pasi Maaranen, Eeva-Maija Kinnunen, Sebastian Dahlbacka, Jussi Jaakkola, Tuija Vasankari, Juhani Airaksinen, Vesa Anttila, Stefano Rosato, Paola D’Errigo, Mikko Savontaus, Tatu Juvonen, Mika Laine, Timo Mäkikallio, Antti Valtola, Peter Raivio, Fausto Biancari
Journal: JAMA Network Open (2019)

<h3>Importance</h3> Transcatheter aortic valve replacement (TAVR) has been shown to be a valid alternative to surgical aortic valve replacement (SAVR) in patients at high operative risk with severe aortic stenosis (AS). However, the evidence of the benefits and harms of TAVR in patients at low operative risk is still scarce. <h3>Objective</h3> To compare the short-term and midterm outcomes after TAVR and SAVR in low-risk patients with AS. <h3>Design, Setting, and Participants</h3> This retrospective comparative effectiveness cohort study used data from the Nationwide Finnish Registry of Transcatheter and Surgical Aortic Valve Replacement for Aortic Valve Stenosis of patients at low operative risk who underwent TAVR or SAVR with a bioprosthesis for severe AS from January 1, 2008, to November 30, 2017. Low operative risk was defined as a Society of Thoracic Surgeons Predicted Risk of Mortality score less than 3% without other comorbidities of clinical relevance. One-to-one propensity score matching was performed to adjust for baseline covariates between the TAVR and SAVR cohorts. <h3>Exposures</h3> Primary TAVR or SAVR with a bioprosthesis for AS with or without associated coronary revascularization. <h3>Main Outcomes and Measures</h3> The primary outcomes were 30-day and 3-year survival. <h3>Results</h3> Overall, 2841 patients (mean [SD] age, 74.0 [6.2] years; 1560 [54.9%] men) fulfilled the inclusion criteria and were included in the analysis; TAVR was performed in 325 patients and SAVR in 2516 patients. Propensity score matching produced 304 pairs with similar baseline characteristics. Third-generation devices were used in 263 patients (86.5%) who underwent TAVR. Among these matched pairs, 30-day mortality was 1.3% after TAVR and 3.6% after SAVR (<i>P</i> = .12). Three-year survival was similar in the study cohorts (TAVR, 85.7%; SAVR, 87.7%;<i>P</i> = .45). Interaction tests found no differences in terms of 3-year survival between the study cohorts in patients younger than vs older than 80 years or in patients who received recent aortic valve prostheses vs those who did not. <h3>Conclusions and Relevance</h3> Transcatheter aortic valve replacement using mostly third-generation devices achieved similar short- and mid-term survival compared with SAVR in low-risk patients. Further studies are needed to assess the long-term durability of TAVR prostheses before extending their use to low-risk patients.
AB1307 STUDY OF CONCORDANCE AND EQUIVALENCE AMONG BARTHEL, LAWTON, HAQ AND BASFI QUESTIONNAIRES IN RHEUMATOID AND SPONDYLOARTHRITIS PATIENTS
Authors: Miguel Angel Belmonte Serrano, Antonio Lozano Saez, Arantxa Conesa, Maria Copovi Moya
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Assessment of functional capacity of patients is usually performed using disease-specific questionnaires for rheumatoid arthritis (HAQ) and for axial spondyloarthropathies (BASFI). However, frequently non disease-specific, general indexes such as Barthel and Lawton-Brody (LB) are used to establish disability in legal environtments and in emergency rooms. Few studies have compared specific vs. generic questionnaires in rheumatic patients (1). <h3>Objectives:</h3> To assess the equivalence between disability questionnaires of generic type, applicable to general population and various diseases (Barthel and LB), with specific questionnaires for rheumatic diseases (HAQ and BASFI). <h3>Methods:</h3> A cross-sectional study was conducted in consecutive outpatients with inflammatory rheumatic diseases (rheumatoid arthritis, psoriatic arthritis, spondyloarthropathies) in usual daily clinical practice in a rheumatology clinic of a tertiary hospital. The patients self-completed the questionnaires (Barthel, LB, HAQ, and BASFI) in a single session. HAQ was only filled by peripheral arthritis patients, while BASFI was only given to spondyloarthropathy subjects. Scores were also computed for SDAI, DAS28 and BASDAI in most patients. Intraclass correlation was used to measure concordance between questionnaires. <h3>Results:</h3> A total of 214 patients where studied. There was good correlation between the scores of the indexes studied, especially between the two general questionnaires (R = 0.45 p &lt;0.01). We observed a high ceiling effect in the scores of both Barthel, (70% of patients obtained values&gt; 95 over a maximum of 100) and Lawton-Brody (60% had values&gt; 23 over a maximum of 24) tests. The disease-specific questionnaires showed a less skewed distribution. The agreement between Barthel's and Lawton's tests was significant when measured by the intraclass correlation (R = 0.48 p &lt;0.01). However, we could not find any significant correlation between the generic questionnaires and the HAQ questionnaire or the BASFI (R &lt; 0.3). <h3>Conclusion:</h3> The Barthel and Lawton-Brody indices show an important ceiling effect in rheumatic patients, and seem to evaluate dimensions of health other than rheumatic questionnaires such as HAQ and BASFI, and thus they are not interchangeable. This point must be taken into account when performing medicolegal or emergency room assessments. Our result is in line with other previous studies(1) <h3>Reference</h3> [1] Zochling J, Stucki G, Grill E, Braun J. A comparative study of patient-reported functional outcomes in acute rheumatoid arthritis. J Rheumatol 2007;34(1):64–9. <h3>Disclosure of Interests:</h3> None declared
Abstract 13813: Intravascular Vagal Nerve Stimulation in Acute Myocardial Infarction Markedly Reduced Infarct Size and Improved Cardiac Function in the Long Term
Authors: Takahiro Arimura, Keita Saku, Takamori Kakino, Takuya Nishikawa, Takeshi Tohyama, Takuya Akashi, Yoshinori Murayama, Takuya Kishi, Tomomi Ide, Kenji Sunagawa
Journal: Circulation (2015)

Backgrounds: In acute myocardial infarction (AMI), the extent of myocardial damage governs the progression to heart failure in the long-term. Therefore, reducing the myocardial damage is prerequisite to prevent chronic heart failure. Although vagal nerve stimulation (VNS) has been repeatedly demonstrated to have the powerful anti-infarct effect, technical difficulties preclude its clinical applications. Recently we developed an new percutaneous, intravascular VNS (iVNS). In this study, we investigated whether iVNS reduces the infarct size and prevents heart failure one month after ischemia reperfusion (IR). Methods: In mongrel dogs, we ligated the left anterior descending coronary artery for 3 hours and reperfused. We transvascularly stimulated the right vagal nerve with a pacing catheter in the superior vena cava. We maximized the intensity of iVNS that did not deteriorate hemodynamics (amplitude; 5.1±2.1 V, pulse width; 0.2ms, frequency; 10 Hz). We started iVNS at the onset of ischemia (iVNS0, n=7) or 90 min after the onset of ischemia (iVNS90, n=7) and continued to 60 min after reperfusion. One month after IR, we compared the infarct size, left ventricular (LV) function and hormonal responses among 3 groups including the no treatment group (IR, n=10). Results: Both iVNS0 and iVNS90 significantly reduced the infarct size (IR: 11.6±3.1, iVNS0: 2.4±2.1, iVNS90: 4.5±1.9%, p&lt;0.05, Figure), improved LV ejection fraction (IR: 50±7, iVNS0: 61±6, iVNS90: 60±5.1%, p&lt;0.05) and decreased LV end-diastolic pressure (IR: 14.6±1.9, iVNS0: 4.2±1.0, iVNS90: 5.0±2.8mmHg, P&lt;0.05). The benefits were larger in iVNS0 than iVNS90. Conclusion: Short term iVNS delivered prior to coronary reperfusion markedly reduced the infarct size and preserved LV function one month after ischemia. Since we can transvascularly deliver iVNS, it may serve as a new non-pharmacological therapeutic strategy and contribute to improve the long term survival in patients with AMI.
Activation of JAK/STAT Signaling in Megakaryocytes Sustains Myeloproliferation <i>In Vivo</i>
Authors: Brittany Woods, Wei Chen, Sophia Chiu, Christian Marinaccio, Chunling Fu, Lilly Gu, Marinka Bulic, Qiong Yang, Anouar Zouak, Shengxian Jia, Praveen Kumar Suraneni, Kailin Xu, Ross L. Levine, John D. Crispino, Qiang Jeremy Wen
Journal: Clinical Cancer Research (2019)

The myeloproliferative neoplasms (MPN), including polycythemia vera, essential thrombocythemia, and primary myelofibrosis, are characterized by the expansion of the erythroid, megakaryocytic, and granulocytic lineages. A common feature of these disorders is the presence of abnormal megakaryocytes, which have been implicated as causative agents in the development of bone marrow fibrosis. However, the specific contributions of megakaryocytes to MPN pathogenesis remain unclear.We used Pf4-Cre transgenic mice to drive expression of JAK2V617F in megakaryocyte lineage-committed hematopoietic cells. We also assessed the critical role of mutant megakaryocytes in MPN maintenance through cell ablation studies in JAK2V617F and MPLW515L BMT models of MPN.JAK2V617F -mutant presence in megakaryocytes was sufficient to induce enhanced erythropoiesis and promote fibrosis, which leads to a myeloproliferative state with expansion of mutant and nonmutant hematopoietic cells. The increased erythropoiesis was associated with elevated IL6 level, which was also required for aberrant erythropoiesis in vivo. Furthermore, depletion of megakaryocytes in the JAK2V617F and MPLW515L BMT models ameliorated polycythemia and leukocytosis in addition to expected effects on megakaryopoiesis.Our observations reveal that JAK/STAT pathway activation in megakaryocytes induces myeloproliferation and is necessary for MPN maintenance in vivo. These observations indicate that MPN clone can influence the behavior of the wild-type hematopoietic milieu, at least, in part, via altered production of proinflammatory cytokines and chemokines. Our findings resonate with patients who present with a clinical MPN and a low JAK2V617F allele burden, and support the development of MPN therapies aimed at targeting megakaryocytes.
David Oliver: Nurses, degrees, and the workforce crisis
Authors: David Oliver
Journal: BMJ (2019)

BerkshireThe biggest threat to the NHS's existence is its workforce crisis.And, although modern healthcare is a team venture reliant on interdisciplinary working, nursing is the NHS's most numerous, visible, and trusted clinical workforce group.One with a workforce crisis even more pressing than that in medicine. 1ainst this backdrop, the zombie trope I've mentioned before in this column 2 -that "overeducated nurses" lead to declining standards of care-has made an unwelcome return in parts of the media.It seems a peculiarly British obsession, as graduate nursing is established in most developed nations-but it's hard to kill off.
Footprints of antigen processing boost MHC class II natural ligand predictions
Authors: Carolina Barra, Bruno Alvarez, Sinu Paul, Alessandro Sette, Bjoern Peters, Massimo Andreatta, Søren Buus, Morten Nielsen
Journal: Genome Medicine (2018)

Major histocompatibility complex class II (MHC-II) molecules present peptide fragments to T cells for immune recognition. Current predictors for peptide to MHC-II binding are trained on binding affinity data, generated in vitro and therefore lacking information about antigen processing. We generate prediction models of peptide to MHC-II binding trained with naturally eluted ligands derived from mass spectrometry in addition to peptide binding affinity data sets. We show that integrated prediction models incorporate identifiable rules of antigen processing. In fact, we observed detectable signals of protease cleavage at defined positions of the ligands. We also hypothesize a role of the length of the terminal ligand protrusions for trimming the peptide to the MHC presented ligand. The results of integrating binding affinity and eluted ligand data in a combined model demonstrate improved performance for the prediction of MHC-II ligands and T cell epitopes and foreshadow a new generation of improved peptide to MHC-II prediction tools accounting for the plurality of factors that determine natural presentation of antigens.
AB0558 TIME OF DIAGNOSTICS OF SJOGREN’S SYNDROME DEPENDING ON ITS FIRST MANIFESTATION
Authors: Olexandr Kuryata, Tetiana Lysunets, Ilona Karavanska, Anastasiia Rytska, Iryna Molokova, Viktor Semenov
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Sjogren's syndrome (SS) is a rare autoimmune disease with multisystem manifestations. Diagnostics of SS is intricate due to its low prevalence and deed of invasive tests for diagnosis confirmation. <h3>Objectives:</h3> To investigate influence of the first symptom of SS on the time of diagnosis establishment. <h3>Methods:</h3> The study was conducted at Dnipropetrovsk Mechnikov Regional Hospital, Dnipro, Ukraine. 23 patients (1 male and 22 females, mean age 54 [47;61] years) with SS that received medical care at Rheumatology Department from 2007<sup>th</sup> to 2017<sup>th</sup> were enrolled to the study. Diagnosis of SS was provided according to American-European Consensus Group criteria (2002). We analyzed time from the first symptom appearance to diagnosis of SS establishment. Symptoms of the disease onset were classified into 4 groups: fever (body temperature&gt;37 C), arthritis (swelling and/or tenderness of ≥1 joints), signs of salivary glands injury (swelling of salivary glands, dry mouth syndrome) and other signs of autoimmune diseases (Rhaynaud's phenomenon, rash, myalgia). <h3>Results:</h3> Median time between the first symptoms and SS diagnostics was 8 [2;17] years. Time to SS diagnostics depending on the first manifestation is in the table below. Presence of fever or symptoms of autoimmune diseases led to faster diagnostics of SS. Presence of salivary glands injury didn't influence time of SS diagnostics, while arthritis enlarged it (Figure 1). <h3>Conclusion:</h3> Fever and signs of autoimmune diseases may be useful in diagnostics of SS. Greater alertness of symptoms of salivary glands injury is needed. <h3>References</h3> [1] Vitali C, Bombardieri S, Jonsson R, et al. Classification criteria for Sjögren's syndrome: a revised version of the European criteria proposed by the American-European Consensus Group. Ann Rheum Dis. 2002;61(6):554-8. <h3>Disclosure of Interests:</h3> None declared
PS1476 APPLICATION OF WHOLE EXOME SEQUENCING FOR PATIENTS WITH INHERITED PLATELET DISORDERS
Authors: M. Stevens‐Kroef, S. de Munnik, W. van Heerde, P. Brons, J. Saes, S. Schols, A. Simons
Journal: HemaSphere (2019)

Background: Inherited platelet disorders (IPDs) are disorders consisting of thrombocytopenia, thromobocytopathy or a combination of these. Diagnosis is often hampered by the lack of specificity and correct validation of current hematological assays. In addition, these disorders exhibit a genetic heterogeneity with over 50 genes involved. Aims: This study evaluates an upfront diagnostic strategy using whole‐exome sequencing (WES) with a targeted analysis of a panel of 145 genes involved in thrombosis and hemostasis in patients suspected for an IPD. Methods: Sixty‐Six patients suspicious for an IPD were subjected to WES, followed by targeted analysis of 145 genes (besides platelet genes also genes involved in coagulation and venous thrombosis embolism are analyzed). Variants were classified according to the five‐tier (class 1 to class 5) scheme. Results: Fourteen patients (21%) harbored (likely) pathogenic variants that explained the clinical spectrum in these patients. Genes affected in these patients were GP9 , MYH9 (2 cases), NBEAL2 , P2RY12 , RUNX1 (3 cases), SLFN14 and VWF (2 cases), all these genes are involved in thrombocytopenia or thromobocytopathy. In the disorders with an autosomal recessive mode of inheritance either the mutation was homozygous ( GP9 and P2RY12) , or compound heterozygous ( NBEAL2 ). Additionally, 2 patients with a mutation in the THPO gene and 1 patient with a mutation in SEPRINC1 were observed, both genes are known to be involved in venous thrombosis. In 4 (6%) other patients only one heterozygous (likely) pathogenic variant of an autosomal recessive disease gene was observed. In 12 patients (18%) a variant of unknown significance (VUS/class 3) was observed. Further segregation studies within the family and functional studies are required to fully solve these cases. Summary/Conclusion: We found that WES is a powerful tool in genetically diagnosing patients with IPD.
SAT0111 RED CELL DISTRIBUTION WIDTH IS A MARKER OF EARLY RESPONSE TO METHOTREXATE IN RHEUMATOID ARTHRITIS
Authors: Daniele Soddu, Mattia Bellan, Erika Zecca, Alessandro Croce, Roberta Pedrazzoli, Daniele Sola, Mario Pirisi, Pierpaolo Sainaghi
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Red blood cell distribution width (RDW) has recently emerged as a possible surrogate biomarker of inflammation. Its potential role as prognostic biomarker has not been evaluated yet in Rheumatoid Arthritis (RA). <h3>Objectives:</h3> The following study aims to evaluate the potential prognostic role of RDW in the prediction of early response to methotrexate (MTX). <h3>Methods:</h3> We performed a retrospective analysis of clinical records of patients affected by RA, according to ACR/Eular classification Criteria. The baseline RDW was recorded and correlated with disease activity scores and inflammatory markers. The response to treatment was evaluated at the 3-months follow-up visit according to Eular response criteria. <h3>Results:</h3> We selected 88 patients (58 females, 65.9%), with a median age of 62 [52-69] years. 61 patients were positive for Rheumatoid Factor (RF) and/or anticitrullinated antibodies – anti-CCP (69.3%). The median DAS28 for Erythrocyte sedimentation rate (DAS28ESR) at the diagnosis was 4.16 [3.33-5.00] while the median RDW was 14.0 [13.1-14.9]%. The baseline RDW was directly associated to CRP (ρ= 0.250; p=0.02), but not with ESR (p=0.32) or DAS28ESR (p=0.40). All the patients received methotrexate (MTX) at a median dose of 10 [10-15] mg/week, 79 (89.8%) also received prednisone (median dose 5 [5-10] mg/day) and 20 hydroxychloroquine in addition to MTX. A significant trend towards a larger RDW was reported from patients with a good Eular response at three months (13.5 [13.0-14.4]%) to those with a moderate response (14.0 [13.2-14.7]%) and finally to those with a poor response (14.6 [13.6-16.0]%; p=0.004). At logistic regression, RDW (p=0.02), but not CRP or ESR (p=0.70 and p=0.37 respectively), was a predictor of a good Eular response. Moreover, in a further logistic regression model, baseline RDW (p=0.03) and baseline DAS28ESR (p=0.0009) were the only predictors of a good Eular response at three months, while age, gender, MTX and prednisone dosage and seropositivity did not fit the model. After the treatment RDW significantly increases (14.7 [14.0-15.7]%) and the variation of RDW from baseline is inversely related to the variation of DAS28ESR (ρ= -0.263; p=0.02). The increase of RDW is significantly higher in patients with a good Eular response, with a trend towards a smaller increase in case of moderate and poor response (0.95 [0.35-1.35]% vs. 0.65 [0.1-1.9]% vs. 0.2 [-0.62-0.77]%; p=0.015). <h3>Conclusion:</h3> RDW is a promising predictor of early response to MTX in RA; in this context, it performs better than classical inflammatory markers. Moreover, RDW significantly increases after MTX initiation, proportionately to response to treatment, suggesting a potential role for RDW as a marker of MTX effectiveness. <h3>Disclosure of Interests:</h3> None declared