tbuckley/cabot-search huggingface dataset:
AB0060 Histopathological Change Caused by Biological Treatment in Rheumatoid Arthritis Synovial Tissue
Authors: A. Kubota, T. Suguro, M. Sekiguchi, S. Ikata, S. Takeuchi, K. Tsuchiya
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> Multiple studies addressing the effects of biologics on the synovial tissue in rheumatoid arthritis (RA) patients have been reported. There are, however, few studies comparing histopathological changes in the synovial tissue in the same RA patients between before and after biologics treatment. <h3>Objectives</h3> We examined biologics impacts on RA synovial tissues based on pathological findings in them collected during surgeries for the same patient before and after biological drug usage. <h3>Methods</h3> Synovial tissues were collected from 22 RA joints before and after biologics. The average age and disease duration of the study subjects were 63.3 and 21.8, respectively. Histopathological changes in the synovial tissues were compared based on Rooney9s score, and presence or absence of fibrinoid degeneration and plasma cell infiltration in the subsynovial tissue. We examined correlation between pathological findings in RA synovium and disease activity under biologics. Disease activity was assessed by CDAI. Etanercept, Infliximab, Tocilizumab, Adalimumab and Abatacept was used as biological drug for 11, 5, 2, 2 and 2 joints respectively. <h3>Results</h3> Rooney score between before and after biological drug usage improved from 30.6 to 12.6 showing significant difference. Significant improvement in Rooney score was observed in all items. Fibrinoid degeneration was observed in 18 cases (81.8%) and 4 cases (18.2%) before and after biologics treatment, respectively, demonstrating a significant reduction with biologics treatment. After biologics treatment, Rooney9s scores in the remission and low disease activity, and moderate disease activity were 7.1 and 15.9, respectively, showing a statistically significant difference. In addition, the moderate disease activity had significantly higher scores in perivascular lymphocytic infiltration, lymphoid follicle and lymphocyte infiltration compared to the remission and low disease activity. Plasma cells after biologics treatment were observed at 0%, 22.2% and 63.3% in the remission, low disease activity and moderate disease activity respectively, indicating the greater disease activities were associated with the more plasma cells in the subsynovial tissue. <h3>Conclusions</h3> The study results demonstrated that biologics treatment significantly ameliorated inflammatory changes in the synovial lining cells and subsynovial tissue. In addition, the results suggested that histopathological findings in the subsynovial tissue reflected disease activity. <h3>Disclosure of Interest</h3> None declared
AML with Inv(3)(q21q26) or t(3;3)(q21;q26) Are Frequently Accompanied by Mutations in RUNX1 and NRAS and Show a High Incidence of NF1 Deletions: a Study On 40 Cases.
Authors: Claudia Haferlach,, Torsten Haferlach, Frank Dicker, Tamara Weiss, Wolfgang Kern, Susanne Schnittger
Journal: Blood (2009)
The Crystal Structure of Abl Kinase with BMS-354825, a Dual SRC/ABL Kinase Inhibitor.
Authors: John S. Tokarski, John Newitt, Francis Y. Lee, Louis Lombardo, Robert Borzilleri, Kevin Kish, Dianlin Xie, Yaqun Zhang, Janet D. Cheng, Susan E. Kiefer, Chieh Ying J. Chang, Herbert E. Klei
Journal: Blood (2004)
Pomalidomide plus low-dose dexamethasone (POM plus LoDEX) versus high-dose dexamethasone (HiDEX) for relapsed or refractory multiple myeloma (RRMM): Overall survival (OS) results of MM-003 after adjustment for crossover.
Authors: Gareth J Morgan, Jesus San Miguel, Sujith Dhanasiri, Dawn Lee, Antonio Palumbo, Thierry Facon, Mohamed H. Zaki, Xin Yu, Lars Axel Sternas, Christian Jacques, Katja C. Weisel, Fritz Offner, Meletios A. Dimopoulos
Journal: Journal of Clinical Oncology (2014)

8593 Background: The pivotal, randomized phase 3 MM-003 trial in patients (pts) with RRMM demonstrated significantly longer median progression-free survival (PFS) with POM + LoDEX (n = 302, 4 months) than with HiDEX (n = 153; 1.9 months; P < 0.0001). Unadjusted median OS was also significantly longer with POM + LoDEX than with HiDEX (HR 0.74; P = 0.0285) despite the crossover of approximately 50% of pts from the HiDEX arm to POM + LoDEX or POM monotherapy. In the presence of extensive crossover, conventional survival analysis methods are biased. Here, we used the 2-stage Weibull method for crossover adjustment to estimate the OS difference between POM + LoDEX and HiDEX. Methods: A 2-stage model was used to estimate counterfactual, adjusted survival data for the HiDEX arm, using a secondary baseline defined by the time of disease progression. To extrapolate the counterfactual data as required by health technology assessment bodies, standard model selection methods were used to identify the best fitting parametric model. Results: Unadjusted median OS in MM-003 was 12.7 and 8.1 months in the POM + LoDEX and HiDEX groups, respectively. After adjusting for crossover, the difference in median OS in the 2 groups was 7.0 months (12.7 vs 5.7 months). Median OS in the POM + LoDEX arm was therefore more than double that in the HiDEX arm. Extrapolation using a log-normal model fitted to the adjusted OS data produced an estimated difference in mean survival times of 14.6 months (28.0 vs. 13.4 months). Predicted survival at 3 years was 21% for pts on POM + LoDEX compared with 8% for pts on HiDEX. Conclusions: The MM-003 intent-to-treat analysis showed a significant increase in median PFS and OS for POM + LoDEX vs HiDEX. The present analysis suggests that OS with POM + LoDEX is double that with HiDEX after accounting for crossover. Extrapolation over a lifetime horizon predicts a mean survival difference between POM + LoDEX and HiDEX of more than 14 months. These data provide important evidence for understanding the clinical efficacy and evaluating the overall economic value of POM in the treatment of RRMM. Clinical trial information: NCT01311687.
Preparticipation predictors for championship injury and illness: cohort study at the Beijing 2015 International Association of Athletics Federations World Championships
Authors: Toomas Timpka, Jenny Jacobsson, Victor Bargoria, Julien D Périard, Sébastien Racinais, Ola Ronsen, Karin Halje, Christer Andersson, Örjan Dahlström, Armin Spreco, Pascal Edouard, Juan-Manuel Alonso
Journal: British Journal of Sports Medicine (2016)

To determine preparticipation predictors of injury and illness at a major Athletics championship.A cohort study design was used. Before the 2015 International Association of Athletics Federations World Championships in Athletics, all 207 registered national teams were approached about partaking in a study of preparticipation health; 50 teams accepted. The athletes (n=957) in the participating teams were invited to complete a preparticipation health questionnaire (PHQ). New injuries and illnesses that occurred at the championships were prospectively recorded. Logistic regression analyses were performed with simple and multiple models using any in-championship injury and in-championship illness as outcomes.The PHQ was completed by 307 (32.1%) of the invited athletes; 116 athletes (38.3%) reported an injury symptom during the month before the championships, while 40 athletes (13%) reported an illness symptom. 20 (6.5%) of the participating athletes sustained a health problem during the championships. Endurance athletes were almost 10-fold more likely to sustain an in-championship illness than speed/power athletes (OR, 9.88; 95% CI 1.20 to 81.31; p=0.033). Participants reporting a preparticipation gradual-onset injury symptom were three times more likely (OR, 3.09; 95% CI 1.08 to 8.79; p=0.035) and those reporting an illness symptom causing anxiety were fivefold more likely (OR, 5.56; 95% CI 1.34 to 23.15; p=0.018) to sustain an in-championship injury.Analyses of preparticipation predictors of injury and illness at a major Athletics championship suggest that endurance athletes require particular clinical attention. Preparticipation symptoms causing anxiety are interesting predictors for in-championship health problems.
PTU-134 Negative Faecal Calprotectin Testing Provides Cost-Effective Diagnostic Reassurance in Patients with Irritable Bowel Syndrome
Authors: K Wright, J Kennedy, LB Materacki, S Waterman, R Makins, A Di Mambro
Journal: Gut (2016)

<h3>Introduction</h3> The diagnosis of irritable bowel syndrome (IBS) requires careful exclusion of ‘red flag’ clinical features and blood abnormalities which may indicate an alternative organic diagnosis such as inflammatory bowel disease (IBD).<sup>1</sup> The chronic, recurrent nature of the symptoms of IBS may lead to diagnostic anxiety. Faecal calprotectin (FC) is a useful non-invasive test for intestinal inflammation that can distinguish IBS from IBD when specialist referral or further investigations are being considered.<sup>2</sup> Confident use of FC is likely to save costs by reducing referral and endoscopy burden. <h3>Methods</h3> This retrospective, observational study investigated the management of patients diagnosed with IBS following gastroenterologist review who had negative FC (&lt;50 µg/g faeces) tested between September 2014 and September 2015. Electronic records were interrogated for clinical letters and the results of blood (full blood count, C-reactive peptide, erythrocyte sedimentation rate/plasma viscosity and coeliac serology), stool and endoscopic investigations. Red flag indicators were defined as per NICE clinical guideline 61.<sup>1</sup> The cost-saving implications of negative FC testing to confirm IBS were evaluated using estimated per person costs of an ELISA test and POCT CalDetect (£22.79), outpatient gastroenterology appointment (£164.00), colonoscopy (£577.68) and flexible-sigmoidoscopy (£351.00).<sup>2,3</sup> <h3>Results</h3> During the study period 173 non-IBD patients (age range: 17–81 y, median: 35 y, 72% female) were referred for gastroenterologist review and had a negative FC test. There were no documented red flag clinical features nor significant abnormalities on blood testing in 30 patients diagnosed with IBS. 23% and 17% of these patients had undergone colonoscopy and flexible sigmoidoscopy respectively. No significant abnormalities were detected. The estimated cost-saving impact of a negative FC to confirm a diagnosis of IBS and limit unnecessary referral and endoscopy was £357.29 per person. <h3>Conclusion</h3> A negative FC may provide cost-effective diagnostic reassurance in patient with suspected IBS without red flag clinical features or blood abnormalities in whom specialist referral or endoscopy is considered. There is a need for FC testing to be made available to primary care physicians with robust pathways to support decision-making. <h3>References</h3> 1 NICE clinical guideline 61 [CG61]. Published February 2008. 2 Faecal calprotectin diagnostic tests for inflammatory diseases of the bowel. NICE diagnostics guidance [DG11]. Published October 2013. 3 Suspected cancer: recognition and management of suspected cancer in children, young people and adults. Clinical guideline appendices A-E. Published June 2015. Commissioned by NICE. <h3>Disclosure of Interest</h3> None Declared
OP0185 Characteristics of Primary Sjögren's Syndrome Patients with IGG4-Positive Plasma Cells in Labial Salivary Glands
Authors: C. Liu, H. Zhang, G. Yao, W. Chen, L. Sun
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> Primary Sjögren9s syndrome (pSS) is a systemic autoimmune disease affecting predominantly exocrine glands such as salivary and lacrimal glands. Immunoglobulin G4 (IgG4)-related disease (IgG4-RD) is a new clinical concept of multi-organ diseases, which is characterized pathologically by the infiltration of IgG4-bearing plasma cells into involved organs. However, some pSS patients showed infiltration of IgG4+ plasma cells in exocrine glands. <h3>Objectives</h3> We aim to investigate the characteristics of primary Sjögren9s syndrome (pSS) patients with IgG4+ plasma cells in labial salivary glands (LSGs). <h3>Methods</h3> 336 patients with pSS were enrolled. The LSG tissues from pSS patients were stained with monoclonal antibodies to IgG4 and IgG. Patients were divided into three subgroups according to histopathologic infiltration degree of IgG4<sup>+</sup> plasma cells. The clinical and serological characteristics of patients were compared. <h3>Results</h3> 336 patients were divided into three groups according to infiltration degree of IgG4<sup>+</sup> plasma cells: slight-IgG4 group (n=194), moderate-IgG4 group (n=106) and high-IgG4 group (n=36). The results showed that the higher IgG4<sup>+</sup> plasma cells expression, the lower positive rates of serum anti-SSA, anti-SSB, anti-nuclear antibodies (ANA) and rheumatoid factor (RF). The comparison of extraglandular manifestations of three groups indicated that patients in high-IgG4 expression group showed a highest frequency of interstitial lung disease (30.6%) and tubulointerstitial nephritis (13.9%), whereas a lowest frequency of leucopaenia (13.9%), thrombocytopaenia (11.1%) and abnormal thyroidal function (0%). <h3>Conclusions</h3> The results showed that a considerable proportion of pSS patients could manifest abundant IgG4+ plasma cells infiltration in LSGs. These patients have unique laboratory and clinical characteristics. These findings may help further understand pSS, IgG4-RD, and the role of IgG4<sup>+</sup> plasma cells in autoimmune diseases. <h3>References</h3> Giovelli RA, Santos MC, Serrano ΈV, Valim V. Clinical characteristics and biopsy accuracy in suspected cases of Sjögren9s syndrome referred to labial salivary gland biopsy. BMC Musculoskelet Disord. 2015; 15;16:30. John HS, Yoh Z, Vikram D: IgG4-related disease. N Engl J Med 2012; 366:539–551. <h3>Disclosure of Interest</h3> None declared
Safety, Tolerability and Dose Response of FBS0701, a Novel Iron Chelator for Treatment of Transfusional Iron Overload: Results of a 24-Week Multicenter, International Phase 2 Study
Authors: Ellis J. Neufeld, Renzo Galanello, Vip Viprakasit, Yesim Aydinok, Antonio Piga, Paul Harmatz, Gian Luca Forni, Farrukh T Shah, Rachael F. Grace, John B. Porter, Elliott Vichinsky, John C Wood, Jennifer Peppe, Amber Jones, Hugh Y Rienhoff
Journal: Blood (2011)
SAT0647-HPR Patient Personality Influences The Prescription of Treatment for Rheumatoid Arthritis
Authors: L. Leon, M. Redondo, A. Garcia-Vadillo, I. Gonzalez-Alvaro, M.A. Perez-Nieto, J.A. Jover, L. Abasolo
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> Individualized treatment of rheumatoid arthritis (RA) based on genetic and serologic factors is increasingly accepted. In addition, patients are more actively involved in the management of their disease. However, personality has received little attention with respect to perception of the need and adherence to treatment. <h3>Objectives</h3> Our objective was to evaluate the influence of personality on the intensity of RA treatment. <h3>Methods</h3> We performed a cross-sectional study in two hospitals with early arthritis clinics where sociodemographic, clinical, and therapeutic variables are systematically recorded. Patients completed Eysenck Personality Questionnaire, Multidimensional Health Locus of Control, Pain-Related Self-Statement Scale and Pain-Related Control Scale. Aggressive treatment was considered if patients received more than two DMARDs or biological agents during the first year of follow-up. Multivariate logistic regression analysis was performed to determine predictors of aggressive treatment. <h3>Results</h3> 176 RA patients were included (80% women, disease begin median age 55 years). Treatment was considered aggressive in 57.9% of the sample. Scores were high in extraversion in 50.8% of patients, neuroticism in 29.5%, and psychoticism in 14.7%.Neuroticism was the only factor associated with aggressive treatment, which was less probable (p=0.04, OR =0.40). Neuroticism also decreased the possibility of receiving a combination of biologics and DMARDs (p=0.04, OR =0.28). <h3>Conclusions</h3> Patients with high scores on neuroticism are more worried, obsessive and hypochondriac, leading them to reject more aggressive therapy. It is important educate patients about their disease so that they will accept more aggressive approaches in clear cases of poor outcome. <h3>Disclosure of Interest</h3> None declared
<i>LPA</i> Gene, Ethnicity, and Cardiovascular Events
Authors: Sang-Rok Lee, Anand Prasad, Yun-Seok Choi, Chao Xing, Paul Clopton, Joseph L. Witztum, Sotirios Tsimikas
Journal: Circulation (2016)

Background: The relationship of LPA single nucleotide polymorphisms (SNPs), apolipoprotein(a) isoforms, and lipoprotein(a) [Lp(a)] levels with major adverse cardiovascular events (MACE) in different ethnic groups is not well known. Methods: LPA SNPs, apolipoprotein(a) isoforms, Lp(a), and oxidized phospholipids on apolipoprotein B-100 (OxPL-apoB) levels were measured in 1792 black, 1030 white, and 597 Hispanic subjects enrolled in the Dallas Heart Study. Their interdependent relationships and prospective association with MACE after median 9.5-year follow-up were determined. Results: LPA SNP rs3798220 was most prevalent in Hispanics (42.38%), rs10455872 in whites (14.27%), and rs9457951 in blacks (32.92%). The correlation of each of these SNPs with the major apolipoprotein(a) isoform size was highly variable and in different directions among ethnic groups. In the entire cohort, Cox regression analysis with multivariable adjustment revealed that quartiles 4 of Lp(a) and OxPL-apoB were associated with hazard ratios (95% confidence interval) for time to MACE of 2.35 (1.50–3.69, P &lt;0.001) and 1.89 (1.26–2.84, P =0.003), respectively, versus quartile 1. Addition of the major apolipoprotein(a) isoform and the 3 LPA SNPs to these models attenuated the risk, but significance was maintained for both Lp(a) and OxPL-apoB. Evaluating time to MACE in specific ethnic groups, Lp(a) was a positive predictor and the size of the major apolipoprotein(a) isoform was an inverse predictor in blacks, the size of the major apolipoprotein(a) isoform was an inverse predictor in whites, and OxPL-apoB was a positive predictor in Hispanics. Conclusions: The prevalence and association of LPA SNPs with size of apolipoprotein(a) isoforms, Lp(a), and OxPL-apoB levels are highly variable and ethnicity-specific. The relationship to MACE is best explained by elevated plasma Lp(a) or OxPL-apoB levels, despite significant ethnic differences in LPA genetic markers.
GPs award potential £700m contract to Virgin Care
Authors: Adrian O’Dowd
Journal: BMJ (2016)

GPs on a clinical commissioning group and local councillors have awarded a contract that could be worth £700m (€810m; $880m) to the private health company Virgin Care to run or oversee 200 types of NHS and social care services to people in Bath and northeast Somerset.

The decision, announced last week, has provoked concern over what is thought will be one of the largest handovers of public services to a private firm to operate when the new arrangements begin in April next year.

Bath and North East Somerset Clinical Commissioning Group (CCG) and Bath and North East Somerset Council announced on 10 November that they had awarded a seven year contract to Virgin Care. The contract, worth £70m a year, …
APOL1–Mediated Cell Injury Involves Disruption of Conserved Trafficking Processes
Authors: Etty Kruzel-Davila, Revital Shemer, Ayala Ofir, Ira Bavli-Kertselli, Ilona Darlyuk-Saadon, Pazit Oren-Giladi, Walter G. Wasser, Daniella Magen, Eid Zaknoun, Maya Schuldiner, Adi Salzberg, Daniel Kornitzer, Zvonimir Marelja, Matias Simons, Karl Skorecki
Journal: Journal of the American Society of Nephrology (2016)

APOL1 harbors C–terminal sequence variants (G1 and G2), which account for much of the increased risk for kidney disease in sub–Saharan African ancestry populations. Expression of the risk variants has also been shown to cause injury to podocytes and other cell types, but the underlying mechanisms are not understood. We used Drosophila melanogaster and Saccharomyces cerevisiae to help clarify these mechanisms. Ubiquitous expression of the human APOL1 G1 and G2 disease risk alleles caused near-complete lethality in D. melanogaster , with no effect of the G0 nonrisk APOL1 allele, corresponding to the pattern of human disease risk. We also observed a congruent pattern of cellular damage with tissue-specific expression of APOL1. In particular, expression of APOL1 risk variants in D. melanogaster nephrocytes caused cell-autonomous accumulation of the endocytic tracer atrial natriuretic factor-red fluorescent protein at early stages and nephrocyte loss at later stages. We also observed differential toxicity of the APOL1 risk variants compared with the APOL1 nonrisk variants in S. cerevisiae , including impairment of vacuole acidification. Yeast strains defective in endosomal trafficking or organelle acidification but not those defective in autophagy displayed augmented APOL1 toxicity with all isoforms. This pattern of differential injury by the APOL1 risk alleles compared with the nonrisk alleles across evolutionarily divergent species is consistent with an impairment of conserved core intracellular endosomal trafficking processes. This finding should facilitate the identification of cell injury pathways and corresponding therapeutic targets of interest in these amenable experimental platforms.
Different Pattern of CD154 and CD40 Expression On B-CLL and T Lymphocytes In Peripheral Blood, Bone Marrow and Lymph Node Microenvironment In B-Cell Chronic Lymphocytic Leukemia (B-CLL)
Authors: Ozren Jaksic, Branimir Gizdic, Tajana Stoos Veic, Vlatka Pandzic Jaksic, Rajko Kusec, Vlatko Pejsa, Branimir Jaksic
Journal: Blood (2010)
Chronic insomnia: diagnosis and non-pharmacological management
Authors: David Cunnington, Moira Junge
Journal: BMJ (2016)

#### What you need to know



 

Surveys of adults show that 13-33% of the adult population have regular difficulty either getting to sleep or staying asleep.1 2 3 Insomnia is dissatisfaction with sleep quantity or quality with one of more of difficulty initiating sleep, difficulty maintaining sleep, and early morning awakening. The sleep disturbance causes significant distress or impairment of functioning. There may be a feeling of having been awake all night even when getting some sleep.

People with comorbid disorders of physical or mental health, such as depression, have higher rates of insomnia. Depression and sleep disturbance are the first and third most common psychological reasons for patient encounters in general practice.4 Untreated, insomnia increases the risk of development or exacerbation of anxiety, depression, hypertension, and diabetes.5 6 This article outlines current concepts in insomnia and provides up to date information on treatment.

Most people will experience sleep disturbance or acute insomnia at some point in any given year. This often occurs around predictable times of stress or when sleep patterns are disrupted, such as with travel, busy periods at work, illness, or emotional upset. While people may be distressed about sleep loss during acute insomnia, once the trigger factors are removed, sleep usually returns to normal.

Insomnia becomes chronic when someone has difficulty either getting to sleep or staying asleep for at least three nights a week (not necessarily every night) for at least three months and is distressed by their sleep symptoms. …
BEAM Versus CEB Conditioning for Autologous Transplantation in Patients with Non-Hodgkin’s Lymphoma and Hodgkin’s Disease: A Single Center Comparative Study of 219 Patients.
Authors: Asad Bashey, Oralia Loza, Bridget Medina, Katherine Keesee, Sue Corringham, Januario Castro, Peter Holman, Thomas A. Lane, Edward D. Ball, Ewa Carrier
Journal: Blood (2005)