tbuckley/cabot-search huggingface dataset:
PB1894 INFECTIOUS RISK AND HYPOGAMMAGLOBULINEMIA IN A MONOCENTRIC REAL LIFE COHORT OF 211 CHRONIC LYMPHOCYTIC LEUKEMIA PATIENTS FOLLOWED FOR 25 YEARS
Authors: R. Murru, G. Caocci, A. Galitzia, S. Uda, F. Culurgioni, S. Oppi, G. La Nasa
Journal: HemaSphere (2019)

Background: Infections represent a major contributor to morbidity and mortality in chronic lymphocytic leukaemia (CLL). Hypogammaglobulinemia (HGG) is a common immune dysfunction in CLL and has been associated with an increased risk of infections. Aims: To analyze impact of HGG on infection free survival (IFS), infectious risk and major infections in a monocentric real life cohort of CLL patients followed for 25 years; to determine impact of IgA deficiency, combined antibody deficiency (CAD) and HGG late onset on infectious death risk. Methods: We retrospectively evaluated 211 unselected CLL patients, diagnosed from 01/1988 to 03/2018, median age 64 years (range 37-88). HGG was evaluated at diagnosis (n = 175), before first line therapy (n = 100) and 12 months after therapy (n = 92). Infection rate during course of disease and infectious morbidity have been collected. Results: During the course of disease 126 patients (60%) underwent at least one infectious event, regardless of severity. Of these, 51 (24%) reported at least one major infectious event (grade ≥3 CTCAE), mainly pneumonitis, skin and soft tissue infections. IgA levels at diagnosis were significantly lower in B and C Binet stage (p = 0.002); IgG (p < 0.001) and IgA levels (p = 0.03) were significantly reduced in patients who experienced infections within 12 months after diagnosis (Fig.1-A); 51 patients (24%) reported major infections and showed reduced IgG and IgA levels at diagnosis (p = 0.01 and p = 0.006, respectively). 25-year IFS for major infections was 67.2% for the entire cohort. Patients in C Binet stage showed significantly lower IFS in comparison with A and B stage (21.5% vs 73.5% and 73.3%, respectively. P < 0.001) (Fig.1-B). In multivariate analysis IGHV unmutated status was associated with lower IFS (p = 0.009). CAD was observed ad diagnosis in 60% of patients with severe infections versus 27% of patients who did not experience these events (p < 0.001). Furthermore, 20.4% of patients developed a late onset CAD with a significant reduction of IFS and an increase of serious infectious events. Overall survival (OS) was heavily reduced by early infectious events occurred during the first year from diagnosis, with higher mortality rate in patients with CAD at diagnosis or late onset; in both cases, risk of infectious death was 10 times higher compared to remaining cohort (p = 0.004).Summary/Conclusion: Our results confirmed the negative impact of HGG on infectious risk and major infections. IgA deficit and CAD were strong predictors for development of these events. Early identification of clinical profile of high risk infections (selective IgA deficit, CAD, late onset HGG) is useful in optimal management of CLL patients.
PS1496 ANKRD26‐RELATED THROMBOCYTOPENIA: STUDY OF 3 FAMILIES
Authors: D. Pereira Coelho, J. Azevedo, P. Martinho, T. Nascimento, S. Marini, A. Barbosa Ribeiro, E. Cortesão, D. Luís, L. Rito, T. Sevivas, R. Guilherme, T. Fidalgo, L. Ribeiro
Journal: HemaSphere (2019)

Background: ANKRD26 ‐related thrombocytopenia ( ANKRD26 ‐RT) is a non‐syndromic form of inherited thrombocytopenia with autosomal dominant transmission, caused by mutations in the 5’UTR region of the ANKRD26 gene. About 8–10% of the patients develop myeloid neoplasms. Recently, in the 2016 revision of the WHO, this entity was recognized in the group of myeloid neoplasms with germ line predisposition and preexisting platelet disorders Aims: Characterization of 3 portuguese families with ANKRD26 ‐RT. Methods: Study of 3 families with thrombocytopenia and ANKRD26 gene mutation. Initial study on NGS platform (Ion Torrent ™, Thermo Fisher Scientific), subsequent confirmation/family studies by Sanger direct sequencing. Clinical (symptoms, treatment, evolution) and laboratory data (platelets, MPV, Hb, leukocytes, bone marrow) were analyzed for 11 individuals. Results: Mutations in the 5’UTR region of the ANKRD26 gene in heterozygosity were found in 11 individuals studied, belonging to 3 families with autosomal dominal familial thrombocytopenia and normal MPV.: c.‐118C&gt;T mutation in family 1 and 2, and the more recently described c.‐140C&gt;G mutation in family 3. Median age at diagnosis of thrombocytopenia was 16 years (0.25–55), with a current median age of 36 years (2–73). In those affected, the median number of platelets is 48x10 9 L (8–203), with persistently normal MPV in 82% of patients (8,2–12,9). In our cohort, the elderly (&gt; 65 years) had lower platelet counts (&lt;15x10 9 L) and 1 family member with the c.‐140C&gt;G mutation had normal platelet count in one determination. About half of the patients had Htc&gt; 45% (max 50.4%). More than half of the patients (54.5%) were initially interpreted as ITP and treated with prednisolone or IV Ig, with no response. Only 5 patients experienced bleeding events, two requiring platelet transfusion. The patient with the most significant hemorrhagic symptoms (45 years old, platelets 15–30x10 9 L) was classified as MDS in 2011. Summary/Conclusion: ANKRD26‐RT is associated with a risk of developing myeloid neoplasia, making its diagnosis and monitoring particularly important. The recognition of this entity is recent and probably underdiagnosed. In our center we identified 3 ANKRD26‐RT families, 2 of them had 3 affected generations. Its characterization and follow‐up will allow us to better understand the variability of presentation and evolution and possibly the identification of bio‐clinical risk factors for neoplastic transformation.
AB0421 METHOTREXATE COMPLIANCE AMONG PATIENTS WITH CHRONIC INFLAMMATORY DISEASE OR CONNECTIVE TISSUE DISEASE
Authors: Elisabeth FILHOL, Charlotte Hua, Francoise Flaisler, Cédric Lukas, Bernard Combe, Jacques Morel, Cecile Gaujoux-Viala
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Methotrexate (MTX) is widely used in rheumatology. About 30% of patients receiving MTX do not respond. One of the explanations could be poor adherence. <h3>Objectives:</h3> The purpose of this study was to assess adherence and to identify predictive factors influencing it. <h3>Methods:</h3> 188 patients with MTX for at least 3 months (rheumatoid arthritis (RA), peripheral spondyloarthritis (PS), psoriatic arthritis (PA), lupus, Sjögren's Syndrome (SS)) were enrolled between May 2017 and May 2018. Each patient completed a questionnaire including socio-demographic data, disease and MTX characteristics, 4-question Morisky, rheumatism activity scores including DAS 28, quality of life (EQ-5D), fibromyalgia (FiRST), anxiety and depression (HADS), catastrophism (PCS-CF), coping (WCC-R) and whether or not to participate in a therapeutic education program. <h3>Results:</h3> 188 were recruited, of which 75% were women, with a mean age of 61.4 +/- 13.24 years: RA (77.12%), PS (7.98%), PA (10.11%), lupus (2.66%) and SS (2.13%). 68.6% were observant, versus 31.4% unobservant minor (28.2%) or major (3.2%) patients. In multivariate analysis, two models were performed and found a poor adherence in case of depression OR: 3.120 [1.051; 9.354], catastrophism OR: 3.974 [1.119; 14.108], anti-CCP antibodies OR: 4.019 [1.277; 12.653] in RA patients and depression OR: 2.715 [1.237; 5.963], absence of comorbidities OR: 2.309 [1.085; 4.915] with all rheumatism. <h3>Conclusion:</h3> Some modifiable factors such as depression and catastrophism were associated with the risk of non-adherence with MTX. It is important to consider depression and catastrophism when taking care of our patients to improve adherence and avoid therapeutic escalations. <h3>Disclosure of Interests:</h3> Elisabeth FILHOL: None declared, Charlotte Hua: None declared, Francoise Flaisler: None declared, Cédric Lukas: None declared, Bernard Combe Consultant for: Abbvie, Bristol-Myers Squibb, Gilead, Janssen, Eli Lilly, MSD, Novartis, Pfizer, Roche-Chugai, Sanofi, UCB, Jacques Morel: None declared, Cecile Gaujoux-Viala Consultant for: Speaking and/or consulting fees from AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, Gilead, Janssen, Merck-Serono, Medac, Nordic Pharma, Novartis, Pfizer, Roche, Sandoz, Sanofi and UCB Pharma., Speakers bureau: Speaking and/or consulting fees from AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, Gilead, Janssen, Merck-Serono, Medac, Nordic Pharma, Novartis, Pfizer, Roche, Sandoz, Sanofi and UCB Pharma.
AB0177 ARE THERE ANY CLINICAL AND SEROLOGICAL DIFFERENCES BETWEEN PATIENTS WITH PRIMARY AND SECONDARY (SLE) ANTIPHOSPHOLIPID SYNDROME?
Authors: Magdalena Dryglewska, Andrzej Majdan, Maria Majdan
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Antiphospholipid syndrome (APS) could be diagnosed as primary (PAPS) or secondary (SAPS - accompanying other diseases, mainly found in patients with systemic lupus erythematosus -SLE) <h3>Objectives</h3> The aim of our study was to determine if pts with PAPS and SAPS had different clinical and serological status. <h3>Methods</h3> The study involved 80 (59-f and 21-m) APS patients (pts) 24 pts had PAPS and 56 pts had APS following SLE. In the whole study group the mean age was: 39.3± 12.7 years (range 18-71), the duration of the disease was 8.8 ± 8.3 years (range 0-37). The presence of aPL was detected in patients' serum using the commercially available tests: aPL-immunodot assay Anti-Phospholipid 10 Dot, for the qualitative detection of IgG or IgM antibodies. The statistical data analysis was performed using Statistica v13.0 <h3>Results</h3> <b>In the study group of 80 patients we have detected the presence of the following aPLs:</b> a- cardiolipin IgM -37%, IgG -50.6%; a-phosphatidic acid IgM -19.7%, IgG -13.3%; a-phosphatidylcholine IgM and IgG -1.2; a-phosphatidylethanolamine IgM -1.2% and IgG -0; a-phosphatidylglycerol IgM – 5.0%, IgG -12.5%; a-phosphatidylinositol IgM-10.0%, IgG-12.5%; a-phosphatidylserine IgM-31.0%, IgG-50.6%; a-annexin V IgM -20%, IgG -10%; a-β2-GP I IgM-44.5%, IgG-35.0%; a-prothrombin IgM -44.5%, IgG-30%. <b>The following clinical symptoms of APS were also present:</b> stroke -10%, arterial/venous thrombosis -34%, pulmonary embolism-16.3%, obstetric complications-25.4%, nephropathy – 30.0%, hypertension-43.8%, valve defects 15.0%, livedo reticularis 11.2%, convulsions/chorea-6.2%, thrombocytopenia- 23.7% of the study group. <b>During the study we detected</b> statistically significant differences in the frequency of occurrence of <b>aPLs between groups with PAPS and SAPS:</b> a-phosphatidylinositol p=0,0345; a-β2-GP I IgM p=0.004; a-prothrombin IgM p=0.0108 a-phosphatidic acid IgM p=0.045 (table 1) There are no differences in the assessed clinical symptoms between pts with PAPS and SAPS, apart from significantly higher frequency of the deep vein thrombosis in pts with PAPS (p- 0.04). <h3>Conclusion</h3> The clinical pictures of PAPS and SAPS are similar. Only deep vein thrombosis occurs more frequently in pts with PAPS. Some classic and novel aPLs occur more frequently in pts with PAPS than in SAPS, and maybe could become a biomarker of PAPS <h3>Disclosure of Interests</h3> Magdalena Dryglewska: None declared, Andrzej Majdan: None declared, Maria Majdan Speakers bureau: MSD, UCB, Abbvie, Roche
PB2416 LABORATORY INVESTIGATION OF HEMOGLOBINOPATHIES IN HUNGARY
Authors: Z. A. Mezei, Z. Bereczky, E. Nagy, P. Antal‐Szalmás, J. Kappelmayer
Journal: HemaSphere (2019)

Background: About 7% of the world population is affected by genetic defects of the hemoglobin molecule, making hemoglobinopathies the number one monogenic disease. Hemoglobinopathies were most common historically in the Mediterranean region and in African and south East Asian populations, but with the increase in migration from the twentieth century they are present worldwide. In Hungary the most common hemoglobinopathy is beta thalassemia, but is not endemic. In the majority of cases, the patients carrying the disease have little or no clinical symptoms. Routine laboratory investigations show a microcytic anemia, but to confirm the diagnosis further laboratory investigations are needed. Aims: To investigate the frequency of the different beta thalassemia mutations in Hungary and to present an algorithm for the investigation of microcytic anemias. Methods: In the period 2005‐2018, overall 3666 patients were investigated with the possible diagnosis of beta thalassemia. In all cases venepuncture was performed, and EDTA anticoagulated blood was collected from the antebrachial vein. Hemoglobin analysis was carried out with a high‐performance liquid chromatography method on a Variant II analyzer (Bio‐Rad, Hercules, CA, USA), and HbA 2 and HbF levels were recorded. From 1704 samples DNA was isolated and Sanger sequencing of the beta globin gene was performed on an ABI Prism 310 Genetic analyzer (Applied Biosystems, Foster City, CA, USA). Results: In 1470 cases (40%), we found elevated HbA 2 and/or HbF levels. In 1704 cases Sanger sequencing was performed and in 804 patients we found a mutation in in the beta globin gene as a cause of beta thalassemia. In 4 cases, a mutation leading to hemoglobin variants with increased O 2 affinity were identified. Janus Kinase 2 (JAK 2) gene exon 12 mutations were not present in these patients with altered O 2 affinity, but elevated hemoglobin and erythrocyte counts were observed, in accordance with the genetic results. Summary/Conclusion: We suggest an algorithm for the investigation of microcytic anemias in regions where the disease is not endemic, along with a few examples from our laboratory. Hemoglobin analysis is important in disorders where beta thalassemia might be suspected like hemolytic anemia, drug induced anemia and hydrops foetalis.
FRI0611 ACUTE AND LONG-TERM EFFICACY OF IL-1 INHIBITOR ANAKINRA IN IDIOPATHIC AND SECONDARY PERICARDITIS IN PATIENTS REFRACTORY OR INTOLERANT TO CONVENTIONAL THERAPY
Authors: Muhammad Hamza Saad Shaukat, Sukhraj Singh, Kathryn Davis, Mikhail Torosoff, Ruben Peredo-Wende
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> In contrast to its use in idiopathic recurrent pericarditis (IRP), efficacy and optimal treatment duration of Anakinra are unclear in pericarditis secondary to known autoimmune or inflammatory conditions. Objectives: a) Assess the efficacy of Anakinra in secondary and idiopathic pericarditis, refractory or intolerant to conventional therapy (CT; colchicine and corticosteroid [CS]). b) Study the effect of extended Anakinra continuation on post-treatment relapse risk. <h3>Methods</h3> Retrospective chart review of 12 adults hospitalised between January 2016 and October 2018 treated with Anakinra 100mg SQ daily for pericarditis refractory or intolerant to CT (CT+A group), and 22 consecutive hospitalised patients treated with CT only (CT group). <h3>Results</h3> Diagnosed autoimmune or inflammatory condition was present in 83.3% (10/12) of CT+A and 40.9% (9/22) of CT group (p=0.07, Table 1). The most common etiologies in CT+A group were RA and Undifferentiated Connective Tissue/Overlap Disease (Figure 1). Despite CT-intolerance or resistance (Figure 2), all CT+A (12/12) patients had symptom relief at discharge vs. 72.7% (16/22) in CT group (p=0.04). There was a strong trend in CT+A compared to CT group towards shorter time to symptom improvement (1.75+/-1.29 vs. 3.55+/-3.06 days; p=0.06) and symptom relief (3.75+/-1.87 vs 5.63+/-3.28 days; p=0.08). CS were tapered successfully in 71.4% (5/7) vs. 66.7% (6/9) of patients in the CT+A and CT groups (p=0.56). Anakinra was associated with a longer mean length of stay (13.0+/-16.2 vs. 8.68+/-5.07 days; p=0.25). No recurrence during treatment was noted in CT+A group (0/12) vs. 40.9% (9/22) in CT group (p=0.009). There was a trend towards reduced post-treatment relapse risk in CT+A group [16.7% (2/12) vs. 41.7% (5/12), p=0.18]. In relapsed patients, there was no significant difference in time to relapse (1.75+/-0.34 vs 1.72+/-0.71 months, p=0.93). Within CT+A group, extended Anakinra use in 6 patients (mean: 5.58+/-6.5 months) did not reduce post-treatment relapse risk [16.7% (1/6) vs 16.7% (1/6), p&gt;0.9]. Adverse effects were infrequent; elevated transaminases (n=1) and local injection-site reaction (n=1). Neither required permanent Anakinra discontinuation. <h3>Conclusion</h3> In hospitalised patients with new-onset or recurrent pericarditis (secondary or idiopathic) refractory or intolerant to CT, Anakinra is associated with improved symptom relief and decreased recurrence risk. Extended continuation of Anakinra after symptom relief does not reduce post-treatment relapse risk. <h3>Disclosure of Interests</h3> None declared
Basal cell carcinoma characterization using fusion <i>ex vivo</i> confocal microscopy: a promising change in conventional skin histopathology
Authors: J. Pérez‐Anker, S. Ribero, O. Yélamos, A. García‐Herrera, L. Alos, B. Alejo, M. Combalia, D. Moreno‐Ramírez, J. Malvehy, S. Puig
Journal: British Journal of Dermatology (2019)

Ex vivo confocal microscopy (CM) works under two modes, fluorescence and reflectance, allowing the visualization of different structures. Fluorescence CM (FCM) requires a contrast agent and has been used for the analysis of basal cell carcinomas (BCCs) during Mohs surgery. Conversely, reflectance CM (RCM) is mostly used for in vivo diagnosis of equivocal skin tumours. Recently, a new, faster ex vivo confocal microscope has been developed which simultaneously uses both lasers (fusion mode).To describe the BCC features identified on reflectance, fluorescence and fusion modes using this novel device. To determine the best mode to identify characteristic BCC features. To develop a new staining protocol to improve the visualization of BCC under the different modes.From September 2016 to June 2017, we prospectively included consecutive BCCs which were excised using Mohs surgery in our department. The lesions were evaluated using ex vivo CM after routine Mohs surgery. The specimens were first stained with acridine orange and then stained using both acetic acid and acridine orange.We included 78 BCCs (35 infiltrative, 25 nodular, 12 micronodular, 6 superficial). Most features were better visualized with the fusion mode using the double staining. We also identified new CM ex vivo features, dendritic and plump cells, which have not been reported previously.Our results suggest that nuclei characteristics are better visualized in FCM but cytoplasm and surrounding stroma are better visualized in RCM. Thus, the simultaneous evaluation of reflectance and fluorescence seems to be beneficial due to its complementary effect. What's already known about this topic? Ex vivo fluorescent confocal microscopy (FCM) is an imaging technique that allows histopathological analysis of fresh tissue. FCM is faster - at least one-third of the time - than conventional methods. FCM has a sensitivity of 88% and a specificity of 99% in detecting basal cell carcinomas (BCCs). What does this study add? Reflectance and fluorescence modes can be used simultaneously in a new ex vivo CM device. Each mode complements the other, resulting in an increase in the detection of BCC features in fusion mode. A combined staining using acetic acid and acridine orange enhances the visualization of tumour and stroma without damaging the tissue for further histopathological analysis.
AB0525 ANTI-SMITH ANTIBODY IS ASSOCIATED WITH DISEASE ACTIVITY IN PATIENTS WITH NEW-ONSET SYSTEMIC LUPUS ERYTHEMATOSUS
Authors: Seungmin Jung, Juyoung Yoo, Sungsoo Ahn, Sangwon Lee, Jason Jungsik Song, Yongbeom Park
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Anti-Smith (Sm) antibody is a highly specific antibody for systemic lupus erythematosus (SLE). Despite the remarkable specificity of anti-Sm antibodies for SLE, the association between anti-Sm antibody level and the clinical manifestation of SLE is still unclear. <h3>Objectives:</h3> We aimed to evaluate the association between anti-Sm antibodies and disease activity in patients with new-onset SLE. <h3>Methods:</h3> We included patients who were repeatedly tested for anti-Sm antibodies at SLE diagnosis and within 12 months after SLE diagnosis. The clinical and laboratory profiles, and SLE disease activity index (SLEDAI) were collected at the time of the anti-Sm antibody test. SLEDAI and laboratory variables associated with disease activity were compared at baseline between patients with and without anti-Sm antibodies. The longitudinal association between disease activity and anti-Sm antibodies was also evaluated in total patients and in those with anti-Sm antibodies. <h3>Results:</h3> Of 92 patients who were tested for anti-Sm antibodies at the time of SLE diagnosis, 67 and another 67 patients were followed up for the presence of anti-Sm antibodies at 6 and 12 months, respectively. Although the baseline SLEDAI was comparable in SLE patients with and without anti-Sm antibodies, the serum anti-Sm antibody level at diagnosis was significantly correlated with SLEDAI (<i>P</i> = 0.003). Patients with anti-Sm antibodies at 12 months had higher SLEDAI and anti-dsDNA levels than those without anti-Sm antibodies (<i>P</i> = 0.002, respectively). The changes in anti-Sm antibody levels over 12 months were also correlated with the alterations in SLEDAI (P = 0.029). <h3>Conclusion:</h3> This study suggests that anti-Sm antibody level is associated with disease activity in patients with new-onset SLE, and that monitoring of anti-Sm antibody levels could help assess the disease activity. <h3>References</h3> [1] Migliorini, P., et al., Anti-Sm and anti-RNP antibodies. Autoimmunity, 2005. 38(1): p. 47-54. [2] Clinical associations of anti-Smith antibodies in PROFILE: a multi-ethnic lupus cohort. Clin Rheumatol, 2015. 34(7): p. 1217-23. [3] What is the clinical significance of anti-Sm antibodies in systemic lupus erythematosus? A comparison with anti-dsDNA antibodies and C3. Clin Exp Rheumatol, 2017. 35(4): p. 598-606. <h3>Disclosure of Interests:</h3> None declared
Deleterious variants in Asian rice and the potential cost of domestication
Authors: Qingpo Liu, Yongfeng Zhou, Peter L. Morrell, Brandon S. Gaut
Journal: Molecular Biology and Evolution (2016)

Many SNPs are predicted to encode deleterious amino acid variants. These slightly deleterious mutations can provide unique insights into population history, the dynamics of selection, and the genetic bases of phenotypes. This is especially true for domesticated species, where a history of bottlenecks and selection may affect the frequency of deleterious variants and signal a “cost of domestication”. Here, we investigated the numbers and frequencies of deleterious variants in Asian rice (Oryza sativa), focusing on two varieties (japonica and indica) and their wild relative (O. rufipogon). We investigated three signals of a potential cost of domestication in Asian rice relative to O. rufipogon: an increase in the frequency of deleterious SNPs (dSNPs), an enrichment of dSNPs compared with synonymous SNPs (sSNPs), and an increased number of deleterious variants. We found evidence for all three signals, and domesticated individuals contained ∼3–4% more deleterious alleles than wild individuals. Deleterious variants were enriched within low recombination regions of the genome and experienced frequency increases similar to sSNPs within regions of putative selective sweeps. A characteristic feature of rice domestication was a shift in mating system from outcrossing to predominantly selfing. Forward simulations suggest that this shift in mating system may have been the dominant factor in shaping both deleterious and neutral diversity in rice.
Abstract 18303: Clinical Outcomes With Beta-blockers in Patients With Myocardial Infarction and Coronary Artery Disease
Authors: Cynthia A Jackevicius, Jack Tu, Peter Austin, David Lash, Maria Koh, Alice Chong, Dennis Ko
Journal: Circulation (2016)

Background: While the benefit of oral beta-blockers in patients with acute myocardial infarction (MI) is established, recent studies have cast doubt on the potential benefit of taking beta-blockers...