tbuckley/cabot-search huggingface dataset:
AB1414-HPR PATIENTS’ EXPERIENCES OF FATIGUE IN AXIAL-SPONDYLOARTHRITIS
Authors: Cecilia Mercieca, Sarah Ryan, Andrew Borg
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Axial spondyloarthritis (ax-SpA) is a chronic inflammatory arthritis that predominantly affects the spine and the sacroiliac joints. Fatigue is recognised as a central ax-SpA symptom. Ax-SpA fatigue is under-explored and often not addressed. Attention in clinical practice seems to be focused on pain and disease activity. <h3>Objectives</h3> The objectives of this study were to explore the meaning, contributing factors and the impact of fatigue on the ax-SpA patients. Self-management and the role of clinicians were also explored. <h3>Methods</h3> A qualitative phenomenological approach was used. A purposive sample of 10 patients with ax-SpA, who were experiencing fatigue (and attending a specialist rheumatology clinic were selected. The participants completed a demographic questionnaire, the Bath ankylosing spondylitis disease activity index (BASDAI) and the Bath ankylosing spondylitis functional index (BASFI) outcome measures. Semi-structured interviews using open-ended questions lasted 30-60 minutes. Interviews were tape-recorded and transcribed verbatim. Data was analysed using Colaizzis framework. Two independent reviewers and 5 participants reviewed the data. <h3>Results</h3> Five males and five females were selected to participate in the study. The mean age was 46.6 years (29 - 69). Seven participants were working. The mean BASDAI was 5.4 and mean BASFI was 5. Most of the participants had disease duration of longer than 5 years. The six themes that emerged from the data are: The meaning of fatigue Fatigue patterns Factors that modulate fatigue The impact of fatigue Self–management of fatigue Professional support. Fatigue was defined as an unpredictable, extreme and persistent tiredness. Fatigue had a cognitive and physical component, which was not related to physical activity and did not resolve by rest or sleep. Fatigue was distinguished from tiredness. Tiredness was perceived as a normal feeling which occurred after physical activity and was resolved by rest or sleep. The severity, duration and frequency of fatigue varied. Fatigue was described as having a multi-factorial aetiology. Fatigue had an overall negative impact upon participants lives affecting their quality of life, leading to psychological and emotional consequences. Participants struggled to self-manage fatigue, receiving no support from health care professionals. <h3>Conclusion</h3> This research has contributed to a better understanding of the patients experiences of ax-SpA fatigue. Fatigue was described as a huge burden and life-changing. Ax-SpA fatigue should be acknowledged in clinical practice. Ax-SpA patients should be asked about fatigue during their clinical consultation. Fatigue should be addressed in its own right and independently from pain and disease activity. <h3>Disclosure of Interests</h3> None declared
How we diagnose and manage altered oxygen affinity hemoglobin variants: Lest we forget <i>JAK2</i> Exon 12 mutation
Authors: Ankit Mangla, Nikki Agarwal
Journal: American Journal of Hematology (2019)

We read with great interest the case studies on altered oxygen affinity hemoglobin variants by Yudin et al. titled ‘How we diagnose and manage altered oxygen affinity hemoglobin variants’ published in the American Journal of Hematology in May of 2019.1 It provides the reader with a concise review of hemoglobinopathies, which constitute a vital part of erythrocytosis investigation. In the second case where the patient presented with polycythemia, JAK2 V617F was appropriately tested and was found to be negative. Here, we would like to emphasize the importance of testing for JAK2 exon 12 mutation which is present in up to 3% of patients who are negative for JAK2 V617F mutation.2 In their cohort of 10 patients, Scott et al. had reported that only six patients matched the criteria of the Polycythemia Vera (PV) Study Group, whereas the rest of them were classified as idiopathic erythrocytosis.3 Similarly, in their cohort of 20 patients, Martinez-Aviles et al., found JAK2 Exon 12 mutation in four patients with JAK2 V617F negative erythrocytosis.4 Although the risk of thrombosis and prognosis is similar between patients with erythrocytosis carrying either of the two mutations, some fundamental differences exist between their presentation.2, 5 The patients with JAK2 exon 12 mutation are younge, and tend to express an exclusive erythroid phenotype with a normal platelet count and white cell count.3-6 In such patients, the bone marrow biopsy shows marked erythroid hyperplasia with normal megakaryocytic and granulocytic lineage.3, 4, 6 The panmyelosis, which is a common feature in JAK2 V617F mutated PV, is usually absent in patients with JAK2 exon 12 mutation.6 The erythropoietin (EPO) levels are also variable where sub-normal to normal EPO levels are reported in patients with JAK2 exon 12 mutated erythrocytosis.3, 4, 6 The patient presented in case two had isolated erythrocytosis, a low normal EPO level, and thrombosis of a dural venous sinus thrombosis, which warrants further testing into JAK2 exon 12 mutation to rule out myeloproliferative disease/neoplasm. We also believe that testing for hemoglobin variants should be included in the workup of myeloproliferative neoplasms, especially in patients presenting only with erythrocytosis. AM and NA developed the manuscript together with equal contributions. The authors do not have any conflict of interest to declare.
Abstract P272: Association of Small Molecule Metabolic Intermediates that Predict Cardiovascular Mortality with Peak VO2 in a Heart Failure Population
Authors: William E Kraus, Mark P Donahue, Svati H Shah, David J Whellan, Anne Hellkamp, Christopher M O’Connor, G. M Felker
Journal: Circulation (2013)

Blood-borne small metabolic intermediates have been associated with disease severity and major adverse coronary events (MACE), including mortality alone, in a cardiovascular disease population. Specifically, short chain dicarboxylacylcarnitines (SCDC), long chain dicaboxylacylcarnitines (LCDC) and long neutral amino acids (LNAA) have been the strongest and most consistent diagnostic and predictive metabolic markers in our CATHGEN cohort. HF-ACTION was a randomized controlled trial of exercise training versus usual care in patients with chronic heart failure (HF) due to left ventricular systolic dysfunction (n=2331). In the study, baseline peak VO 2 was the most significant predictor of mortality in the this population ( X 2 =153). We hypothesized that small molecule blood-borne metabolic intermediates would be associated with peak VO 2 in HF-ACTION. Peak VO 2 was measured using a standard protocol across 82 centers and quality control was ensured in a core laboratory. We measured 15 amino acids and 45 acylcarnitines from baseline plasma samples in 447 individuals in the Duke Stedman Metabolomics Laboratory. The 60 metabolites were reduced into 13 independent factors using principal components analysis that accounted for a total of 43.8% of the total variance in these sample analytes. We assessed the ability of metabolite factors to predict baseline peak VO 2 in the presence of covariates modeled as significant predictors in previous published work in this population (age, gender, race, region, BMI, diabetes, PVD, NYHA Class, LVEF, ventricular conduction and test modality—bicycle or treadmill). Five metabolite factors were significant predictors of peak VO 2 , the three strongest being SCDC (estimate in SD factor score per mL/kg/min (VO 2 ) = -1.004; p-value=0.002), LNAA (0.583; p=0.003); and LCDC (-0.903; p=0.008). The direction of change with increased peak VO 2 (related to decreased mortality in HF-ACTION) were consistent with the relation of metabolites to decreased mortality in CATHGEN. Thus, three classes of metabolic intermediates that are associated with MACE in a cardiovascular cohort study also were associated with functional capacity (peak VO 2 ). To the best of our knowledge this is the first description of molecular metabolic biomarkers that independently related, even with our strongest clinical variables in the model, to functional capacity in HF. These metabolic intermediates may be functionally related to the reductions in functional capacity in HF and therefore serve as potential targets for new diagnostics or therapeutic interventions.
Abstract 14622: Infections in Patients With a Total Artificial Heart May Be Common but Rarely Fatal
Authors: Luis F Hidalgo, Keyur B Shah, Richard H Cooke, Daniel G Tang, Vigneshwar Kasirajan, Howard A Cooper, Wilbert S Aronow
Journal: Circulation (2016)

Background: Infectious complications are common in patients with durable left ventricular assist devices. However, data on infections in patients with a total artificial heart (TAH) are limited. Ob...
PB2323 CORRELATION BETWEEN COLONIZATION AND BACTERAEMIA FROM MULTIDRUG RESISTANT SPECIES IN PATIENTS UNDERGOING HEMATOPOIETIC CELL TRANSPLANTATION
Authors: M. Liga, D. Aggelinas, N. Spyridis, K. Lekka, C. Korovila, F. Paliogianni, M. Marangos, A. Spyridonidis
Journal: HemaSphere (2019)

Background: Bacterial infections from multidrug resistant pathogens are an important cause of morbidity and mortality of patients undergoing hematopoietic cell transplantation (HCT). Aims: Aim of this study was to record bacteremia's from multidrug-resistant bacteria in the first hospitalized period of transplantation and their correlation with the patient's colonization. Methods: The prospective analysis includes 24 consecutive patients (14 males, 10 females), with median age of 45 years (range 24-72) who underwent HCT (21 allogeneic, 3 autologous) during 1/1/2018-15/8/2018. All patients were tested for colonization from multidrug resistant Klebsiella Pneumoniae Carbapenemase (KPC+) and Vancomycin Resistant Enterococcus (VRE+) with rectal smear and urine culture upon their hospitalization in the unit and before the start of the conditioning regimen. All patients received ciprofloxacin prophylaxis. We analyzed the bacteremia's during the first hospitalization in the Bone Marrow Transplantation Unit, approximately until day 30 after transplantation. Results: Twelve from 24 (50%) patients were found colonized with multidrug resistant pathogens upon their entry into the unit (Table 1). A total of 19 different bacteremia's occurred in 13 patients. Of the 9 non-colonized patients’ no one experienced episode of multidrug resistant KPC or VRE bacteremia. From the 6 KPC+ patients, all of them (100%) showed bacteremia, 3/6 (50%) KPC bacteremia and 3/6 bacteremia from other pathogen than KPC (Pseudomonas Aeruginosa-MBL, Staph. Epidermidis). Of the 9 VRE+ patients, 4 showed bacteremia and none (0%) showed VRE bacteremia. No mortality due to bacteremia was observed.Summary/Conclusion: There is a high rate of colonization from multi-resistant KPC and VRE in heavily treated patients referred for transplantation. Non-colonized patients did not experience KPC or VRE bacteremia, reflecting high prophylactic measures in a transplant unit. KPC colonization is associated with a remarkable (50%) probability of bacteremia from the same multidrug resistant pathogen. Our results demonstrate the importance of urine and rectal smear control for colonization with KPC in patients who are going to receive HSCT, as this can be used for targeted antibiotic treatment in case of the occurrence of febrile neutropenia
Genomic Evidence of Widespread Admixture from Polar Bears into Brown Bears during the Last Ice Age
Authors: James A Cahill, Peter D Heintzman, Kelley Harris, Matthew D Teasdale, Joshua Kapp, Andre E R Soares, Ian Stirling, Daniel Bradley, Ceiridwen J Edwards, Kiley Graim, Aliaksandr A Kisleika, Alexander V Malev, Nigel Monaghan, Richard E Green, Beth Shapiro
Journal: Molecular Biology and Evolution (2018)

Recent genomic analyses have provided substantial evidence for past periods of gene flow from polar bears (Ursus maritimus) into Alaskan brown bears (Ursus arctos), with some analyses suggesting a link between climate change and genomic introgression. However, because it has mainly been possible to sample bears from the present day, the timing, frequency, and evolutionary significance of this admixture remains unknown. Here, we analyze genomic DNA from three additional and geographically distinct brown bear populations, including two that lived temporally close to the peak of the last ice age. We find evidence of admixture in all three populations, suggesting that admixture between these species has been common in their recent evolutionary history. In addition, analyses of ten fossil bears from the now-extinct Irish population indicate that admixture peaked during the last ice age, whereas brown bear and polar bear ranges overlapped. Following this peak, the proportion of polar bear ancestry in Irish brown bears declined rapidly until their extinction. Our results support a model in which ice age climate change created geographically widespread conditions conducive to admixture between polar bears and brown bears, as is again occurring today. We postulate that this model will be informative for many admixing species pairs impacted by climate change. Our results highlight the power of paleogenomics to reveal patterns of evolutionary change that are otherwise masked in contemporary data.
AB0341 REASONS FOR DROP-OUT IN RHEUMATOLOGY SPECIALTY CARE OF ELDERLY RHEUMATOID ARTHRITIS PATIENTS
Authors: Shinichi Mizuki
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> The difference between total and healthy life expectancies were 12.3 and 8.8 years for women and men respectively in 2016, in Japan. Rheumatoid arthritis (RA) not only reduces daily living activities due to joint symptoms but also deteriorates the life prognosis due to systemic inflammation. That is, patients with RA are short for both total and healthy life expectancy. In recent years, the need for rheumatologist to provide specialty medical care to elderly patients with RA has been expanding. However, some elderly patients drop out of specialty treatment and care. To date, there are little information concerning background of patients who drop out. <h3>Objectives</h3> To investigate reasons and characteristics of elderly RA patients who drop out from rheumatology specialty medical care. <h3>Methods</h3> Of RA patients who had been visited our rheumatology specialty facility in 2016, we defined as drop-out when the patients did not return to the hospital in 2017. We surveyed age, gender, disease activity, and reason for drop-out retrospectively from medical records and questionnaires. <h3>Results</h3> Of 2,092 patients with RA who visited to our department, 156 patients (7.5%, 95% confidential interval: 6.4 – 8.6%) dropped out. Among drop-out patients, 101 patients were older than 65. 37 patients (37%) dropped out due to comorbidities including death (group C), 32 (32%) patients were introduced certified rheumatologists near the patients' residences (group R). Twenty-two patients were due to unknown reasons, nine were due to remission, and one patient moved out to other area. Average age of both group C and R were eighty years old. Glucocorticoid user rate (C: 89%, R: 71%) and dose (C: 5.6 mg, R: 5.7 mg) were similar in the both two groups. Patients in group C showed less use of methotrexate (C: 19% vs R: 58%, P &lt; 0.01) compared with group R patients. Simple disease activity index was similar, however, higher modified health assessment questionnaire was observed in group C patients (C: 1.13 vs R: 0.25, p=0.01). <h3>Conclusion</h3> Some elderly RA patients, especially may drop out from rheumatology specialty care due to comorbidities. Regional co-management should be constructed so that elderly patients could continue receiving RA specialized care. <h3>Disclosure of Interests</h3> None declared
SP0039 WIN: DE-CONVOLUTING THE COMPLEXITIES OF SLE – RECENT INSIGHTS INTO THE PATHOGENESIS
Authors: Mary K. Crow
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> SLE remains one of the most complex diseases in medicine, with protean alterations in immune system function contributing to autoimmunity, tissue inflammation and damage, and diverse clinical manifestations. While considerable advances in understanding the molecular pathways and mediators involved in SLE have led to identification of rational therapeutic targets, a full understanding of the upstream etiologic drivers of the disease and how genetic risk and environmental stimuli shape the evolution of the disease and its clinical heterogeneity requires continued investigation. <h3>Objectives:</h3> To review recent literature relevant to the etiology, pathogenesis and heterogeneity of SLE. <h3>Methods:</h3> Review and synthesis of recent literature. <h3>Results:</h3> Recent advances in characterizing the mechanisms of regulation and degradation of endogenous nucleic acids, particularly insights derived from disorders based on a variety of single gene mutations that result in production of type I interferon, suggest potential drivers of type I interferon production in SLE. The functional alterations in many aspects of T and B cell function in patients with SLE, some attributable to type I interferon, continue to be identified. Potential contributions of the microbiome expand our view of candidate disease-enhancing factors. Interest in defining patients at risk for evolving from pre-clinical to clinical disease that fulfills classification criteria for SLE may help to identify the essential elements of lupus pathogenesis and suggest approaches for disease prevention. <h3>Conclusion:</h3> Endogenous nucleic acids have emerged as compelling candidates for drivers of lupus pathogenesis, along with their traditional role as antigenic targets of lupus autoantibodies. Although the clinical heterogeneity of SLE has confounded efforts to successfully test new therapies, advances in identifying sources of nucleic acids stimulating type I interferon and alterations in adaptive immune system function help us move toward a synthetic understanding of disease pathogenesis and suggest that therapeutic regimens targeting both innate and adaptive immune systems might be required to control or prevent disease. <h3>References:</h3> [1] Crow MK, Olferiev M, Kirou KA. Type I interferons in autoimmune disease. Annu Rev Pathol. 2019 [2] Uggenti C, Lepelley A, Crow YJ. Self-awareness: Nucleic acid-driven inflammation and the type I interferonopathies. Annu Rev Immunol. 2019. <h3>Disclosure of Interests:</h3> None declared
AB1139 CONTRIBUTION OF CERVICAL SPINE IMAGING IN RHEUMATOID ARTHRITIS
Authors: ACHEK Mohamed Amine EL, Amel Farhat, Chakib Kraeim
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Cervical involvement in rheumatoid arthritis (RA) ranks third after erosive lesions of the hands and feet. The evolution is unpredictable and imposes regular radio-clinical surveillance because of the frequency of asymptomatic forms and of its seriousness, especially the neurological involvement could threaten functional and vital prognosis. <h3>Objectives</h3> To specify the contribution of imaging means in the diagnosis of rheumatoid cervical involvement and perform a comparison of these different imaging means to establish an exploration strategy. <h3>Methods</h3> This is a cross-sectional and descriptive retrospective study of 55 patients with RA which evolves since more than two years. All patients were explored by standard radiographs. CT and/or cervical MRI were performed according to the radiological findings. <h3>Results</h3> The mean age of the patients was 57.55 ± 13.59 years with a female predominance (72.7%). Functional signs were dominated by neck pain (87.3%). The stiffness of the cervical spine was the most recovered physical sign (69.1%). In imaging, cervical involvement was dominated by atloido-axoidal subluxations (AAS) in 50.9% and pannus of C1-C2 (14.54%). Among AAS, anterior AAS was the most common (40%) followed by vertical AAS (7.27%) then lateral and rotary (both in 1.81%). Subaxial subluxation was found in 14.54% of cases. Standard radiographs detected 38.2% of previous AAS versus 20% on MRI. CT allowed a better study of rotatory and lateral subluxations. MRI detected pannus of C1-C2 and assessed the neurological impact of the various cervical rheumatoid lesions. <h3>Conclusion</h3> Clinical examination alone remains insufficient in the evaluation of the rheumatoid cervical spine. Imaging has thus emerged as a key examination in exploration and therapeutic orientation. The standard radiography with its different incidences is the first-line examination. CT and MRI will be discussed as second-line. CT essentially detects atypical subluxations and bone lesions. MRI is the exam of choice for the study of pannus and neurological repercussions. <h3>References</h3> [1] Currier B, Coblyn J. Cervical subluxation in rheumatoid arthritis. Available at:https://www.uptodate.com/contents/cervical-subluxation-in-rheumatoid-arthritis. Accessed March 23, 2018 <h3>Disclosure of Interests</h3> None declared
Developmental Loci Harbor Clusters of Accelerated Regions That Evolved Independently in Ape Lineages
Authors: Dennis Kostka, Alisha K Holloway, Katherine S Pollard
Journal: Molecular Biology and Evolution (2018)

Some of the fastest evolving regions of the human genome are conserved noncoding elements with many human-specific DNA substitutions. These human accelerated regions (HARs) are enriched nearby regulatory genes, and several HARs function as developmental enhancers. To investigate if this evolutionary signature is unique to humans, we quantified evidence of accelerated substitutions in conserved genomic elements across multiple lineages and applied this approach simultaneously to the genomes of five apes: human, chimpanzee, gorilla, orangutan, and gibbon. We find roughly similar numbers and genomic distributions of lineage-specific accelerated regions (linARs) in all five apes. In particular, apes share an enrichment of linARs in regulatory DNA nearby genes involved in development, especially transcription factors and other regulators. Many developmental loci harbor clusters of nonoverlapping linARs from multiple apes, suggesting that accelerated evolution in each species affected distinct regulatory elements that control a shared set of developmental pathways. Our statistical tests distinguish between GC-biased and unbiased accelerated substitution rates, allowing us to quantify the roles of different evolutionary forces in creating linARs. We find evidence of GC-biased gene conversion in each ape, but unbiased acceleration consistent with positive selection or loss of constraint is more common in all five lineages. It therefore appears that similar evolutionary processes created independent accelerated regions in the genomes of different apes, and that these lineage-specific changes to conserved noncoding sequences may have differentially altered expression of a core set of developmental genes across ape evolution.
Authors’ response: Chikungunya infection in travellers to Thailand: additional United Kingdom cases identified by specialist laboratory
Authors: Emilie Javelle, Davidson H Hamer, Vanessa Field, Shilan Jmor, Philippe Gautret
Journal: Eurosurveillance (2019)

Preview this article: Authors’ response: Chikungunya infection in travellers to Thailand: additional United Kingdom cases identified by specialist laboratory, Page 1 of 1 < Previous page | Next page > /docserver/preview/fulltext/eurosurveillance/24/24/eurosurv-24-24-6-1.gif
αv vitronectin receptors in vascular‐mediated disorders
Authors: Shaker A. Mousa
Journal: Medicinal Research Reviews (2002)

Abstract Various integrin antagonist candidates including antibodies, cyclic peptides, peptidomimetics, and non‐peptides have been clinically evaluated and shown to successfully modulate certain disease processes. This review will focus on the key role of the αv integrin (αvβ3 and αvβ5) in vascular disorders such as restenosis and angiogenesis‐mediated disorders. © 2002 Wiley Periodicals, Inc. Med Res Rev, 23, No. 2, 190–199, 2003