tbuckley/cabot-search huggingface dataset:
PTU-079 Effect of Inflammation on Liver Stiffness in Active Autoimmune Liver Disease: A Simultaneous Biopsy-Controlled Study Using Acoustic Radiation Force Impulse (ARFI) Elastography
Authors: DI Sherman, W Fateen, M Jagtiani Sangwaiya, P Tadrous, P Shorvon
Journal: Gut (2016)

<h3>Introduction</h3> ARFI elastography (virtual touch quantification,VTq<b>™) </b>is a well validated technique for non-invasive assessment of liver fibrosis in viral hepatitis. The interpretation of shear velocity readings in active autoimmune liver disease (AILD) may be affected by a number of factors. However, few studies have specifically examined the effect of inflammation on liver stiffness (LS) in this group. We report the results of a preliminary study in which LS and histology have been sampled simultaneously from the same region of liver tissue in a large cohort with active AILD. <h3>Methods</h3> Our local database of 101 patients with AILD (63 autoimmune hepatitis AICH +/- overlap, 38 cholestatic-PBC or PSC) was investigated. LS estimation by ARFI was performed using a standard validated protocol by a single operator. Biopsies were performed from the same region of liver using an 18 G Biopince™ needle, immediately after LS measurement. Clinical, biochemical, ultrasonic and histopathological data were collated retrospectively. ARFI/histological variance (AHV) was defined as a difference of more than 1 Metavir or 2 Ishak stages from that predicted by ARFI, according to standard calibration.<b><sup>1</sup></b> <h3>Results</h3> Sixty one ARFI + liver biopsies performed at the same session were identified out of a total of 164 ARFI and 114 liver biopsies. Patients included group 1: 37 active AICH (diagnosis/flare on therapy); group 2: 7 AICH remission; and group 3: 17 cholestatic liver disease. Co-pathology was seen in 8. Standard ARFI quality measures were validated in 93%. Mean ARFI shear velocities were significantly higher in group 1 compared with 2 and 3–2.41, 1.29 and 1.64 m/sec, respectively (p = 0.001). AHV occurred in 44.1, 28.6 and 29.4%, AHV prevalence was 41% overall, with 100% in group 1 and 88% overall reflecting overestimation of fibrosis. Across all groups, Ishak necro-inflammatory grade was strongly correlated with both ARFI shear velocity (r = 0.58,p &lt;0.0001) and also AHV (r = 0.35, p = 0.006) by Spearman analysis. ALT showed a weaker correlation with AHV (r = 0.25, p = 0.06). <h3>Conclusion</h3> These data show that variance between ARFI shear velocity and histology is common in active AILD, usually overestimating predicted fibrosis stage. Strong positive correlations were seen between histological inflammatory grade with both shear velocity and AHV, suggesting that inflammation is implicated in the observed increase in LS in this group. Confirmation of this association in further studies would suggest a potential role for ARFI elastography in monitoring resolution of inflammation during treatment of AILD. <h3>Reference</h3> 1 D. Sherman, <i>et al</i>. <i>J Hepatol</i> 2014;<b>60</b>(Suppl 1):S413. <h3>Disclosure of Interest</h3> None Declared
AB0242 IL6 Genetic Variants and IGA-RF as Markers of Erosiveness at Onset in Early Rheumatoid Arthritis
Authors: S. Canestri, A.L. Fedele, B. Tolusso, L. Petricca, S. Alivernini, M.R. Gigante, E. Gremese, G. Ferraccioli
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Objectives</h3> To determine whether genetic variants in the loci of interleukin-6 (IL-6) are associated with clinical and biologic phenotypes of Rheumatoid Arthritis (RA). <h3>Methods</h3> Three hundred and forty five early RA (ERA) patients were enrolled in this study (76.2% female; mean age: 54.4±14.1 years; 33.6% VERA). 239 patients (69.3%) were seropositive for at least one antibody: 62.9% ACPA, 48.7% RF -IgM and 33.0% RF-IgA positive, respectively. At diagnosis, 101 subjects (29.3%) had detectable erosions in hands and feet radiographs. All patients were treated according to a tight control strategy (Methotrexate for 3 months, and if an incomplete response was reached after 3 months a combination with Tumor Necrosis Factor (TNF) blockers was started) and at each visit, clinical remission was evaluated according to ACR/EULAR criteria (Felson DT et al. Arthritis Rheum 2011). ERA patients were genotyped for IL6–174G/C polymorphism by PCR and compared with a cohort of healthy subjects (n=293). <h3>Results</h3> The frequency of C allele of the IL-6–174G/C SNP was higher in ERA patients (30.7%) compared to healthy controls [23.7%; OR (95%CIs): 1.43 (1.11–1.83)], while the GG genotype was present in 49.6% of ERA and in 59.4% of control subjects [OR (95%CIs): 0.67 (0.49–0.92)] respectively. At baseline, ERA patients carriers of the GG genotype were more likely seropositive compared to patients carrying the C allele [74.9% vs 63.8%, p=0.03], mainly for the IgA-RF positivity [38.6% vs 27.7%; OR (95%CIs): 1.64 (1.04–2.57)]. At diagnosis, IgA-RF positive ERA patients were more likely erosive than IgA-RF negative ones [33.1% vs 25.2%; OR (95%CIs):1.80 (1.11–2.95)]. Conversely, radiographic damage was not associated with gender, symptoms duration, smoking habit, positivity for ACPA or IgM-RF antibodies and disease activity. The percentage of erosive disease increased to 39.6% in ERA patients IgA-RF + carrying the GG genotype compared to the others (24.7%; OR (95%CIs): 2.002 (1.23–3.26)], with a lower presence of radiographic damage in carriers of C allele and IgA-RF negative (12.5%). Finally, patients carrying C allele of IL6–174G/C SNP and IgA- RF negative at diagnosis, were less prone to develop erosions over time than subjects with at least one risk factor (8.0% vs 19.1%, respectively, p=0.02). <h3>Conclusions</h3> In our cohort of ERA patients, the presence of C allele of IL6–174G/C SNP associates with RA susceptibility whereas the GG genotype associates with seropositivity for IgA-RF and erosions. These data add new information about the biology underlying the development of radiographic damage in the early phases of RA. <h3>Disclosure of Interest</h3> None declared
Can I have cheese on my ham sandwich?
Authors: Kaustubh G Joshi
Journal: BMJ (2016)

“Can I have cheese on my ham sandwich?” My patient asked me this question several times during the first few weeks of my employment at a state hospital. Although dieticians provided recommendations, I was ultimately responsible for entering dietary orders. Like most patients on the ward, my patient was prescribed psychotropic drugs that resulted in metabolic complications. As a result, she …
Costs of perennial allergic rhinitis and allergic asthma increase with severity and poor disease control
Authors: M. Belhassen, P. Demoly, E. Bloch‐Morot, G. de Pouvourville, M. Ginoux, A. Chartier, L. Laforest, N. Serup‐Hansen, M. Toussi, E. Van Ganse
Journal: Allergy (2016)

Perennial allergic rhinitis (PAR) represents a global and public health problem, due to its prevalence, morbidity, and impact on the quality of life. PAR is frequently associated with allergic asthma (AA). Costs of PAR with or without AA are poorly documented.Our study aimed to detail medical resource utilization (MRU) and related direct cost for PAR, with or without concomitant AA, in France.Using Electronic Health Records (EHRs), we identified in 2010 two cohorts of PAR patients, based on General Practitioners' diagnoses and prescribing data, with and without concomitant AA. For each patient, the EHRs were linked to corresponding claims data with MRU and costs during years 2011 to 2013. Predefined subgroup analyses were performed according to severity of PAR and level of AA control.The median annual cost reimbursed by social security system for a patient with PAR, and no AA was 159€ in 2013. This varied from 111€ to 188€ depending on PAR severity. For patients with PAR and concomitant AA, the median annual cost varied between 266€ and 375€, and drug treatment accounted for 42-55% of the costs, depending on asthma control.This study linking diagnoses from EHRs to claims data collected valid information on PAR management, with or without concomitant AA, and on related costs. There was a clear increase in costs with severity of PAR and control of AA.
A Phase II Study of Intravenous Azacitidine Alone in Patients with Myelodysplastic Syndromes NCT00384956.
Authors: Richard Walgren, Crystal Dao, Frederieke Kreisel, Peter Westervelt, Camille Abboud, Timothy Graubert, Amanda Cashen, Geoffrey Uy, Feng Gao, John DiPersio, Ravi Vij
Journal: Blood (2007)
Tumor Thickness and Mitotic Rate Robustly Predict Melanoma-Specific Survival in Patients with Primary Vulvar Melanoma: A Retrospective Review of 100 Cases
Authors: Priyadharsini Nagarajan, Jonathan L. Curry, Jing Ning, Jin Piao, Carlos A. Torres-Cabala, Phyu P. Aung, Doina Ivan, Merrick I. Ross, Charles F. Levenback, Michael Frumovitz, Jeffrey E. Gershenwald, Michael A. Davies, Anais Malpica, Victor G. Prieto, Michael T. Tetzlaff
Journal: Clinical Cancer Research (2016)

Purpose: Primary vulvar melanoma (PVM) is the second most common vulvar malignancy. Despite their distinct anatomic site and unique molecular-genetic alterations, PVMs are staged according to the American Joint Committee on Cancer (AJCC) guidelines for primary cutaneous melanomas (PCM). However, whether parameters derived for PCM also apply to PVM remain a critical yet largely unexplored clinical question. The objective of this study was to determine the parameters predictive of survival in PVM.Experimental Design: We retrospectively reviewed 100 patients with PVM and determined associations between clinical and histopathologic parameters and disease-specific survival (DSS) and overall survival (OS).Results: Univariate Cox regression analysis demonstrated older age (>56 years), greater tumor thickness, higher dermal mitotic rate, ulceration, lymphovascular invasion, perineural invasion, microscopic satellitosis, and absence of precursor nevus associated with decreased OS. Furthermore, age, midline, and/or multifocal involvement, greater tumor thickness, higher dermal mitotic rate, ulceration, lack of regression, lymphovascular invasion, perineural invasion, and microscopic satellitosis associated with decreased DSS. Multivariate analysis demonstrated tumor thickness, dermal mitotic rate, lymphovascular invasion, microscopic satellitosis, and absence of precursor nevus independently predicted shorter OS. Only tumor thickness and increased dermal mitotic rate (≥2/mm2) independently predicted reduced DSS. In comparison with the AJCC T-category, a novel, bivariate T-category based only on tumor thickness and dermal mitotic rate robustly predicted OS and DSS in our patient cohort.Conclusions: In the largest single institutional study of PVM, we demonstrate a combination of tumor thickness and mitotic rate comprise a simple but robust T-category to direct staging and prognosis. Clin Cancer Res; 23(8); 2093-104. ©2016 AACR.
Risk of Transformation of Follicular Lymphoma to High Grade Lymphoma After Radioimmunotherapy: A Prospective Observational Single Institutional Experience
Authors: Brian L. Burnette, Gregory Wiseman, Thomas M. Habermann, William R Macon, Stephen M. Ansell, David James Inwards, Ivana N. Micallef, Patrick B. Johnston, Kay M. Ristow, Thomas E. Witzig, Grzegorz S. Nowakowski
Journal: Blood (2011)
Remission Rates In Childhood Acute Myeloid Leukemia (AML) Utilizing a Dose-Intensive Induction Regimen with or without Gemtuzumab Ozogamicin (GO): Initial Results From the Children's Oncology Group Phase III Trial, AAML0531
Authors: Alan S Gamis, Todd A Alonzo, Robert B Gerbing, Richard Aplenc, Lillian Sung, Soheil Meshinchi, Susana C. Raimondi, Betsy A. Hirsch, Samir Kahwash, Amy Heerema-McKenney, Laura Winter, Kathleen Glick, Patti Byron, Laura Burden, Tanya Wallas, Stella M. Davies, Franklin O. Smith
Journal: Blood (2010)
AB0720 The Characteristics of Andersson Lesions (Spondylodiscitis) Based on Whole Spine Magnetic Resonance Imaging in Ankylosing Spondylitis
Authors: S.-K. Kim, K. Shin, Y. Song, S. Lee, T.-H. Kim
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> Andresson lesions could cause debilitating pain and functional impairment in ankylosing spondylitis (AS) patients. <h3>Objectives</h3> The objective of this study was to identify the characteristics of Andersson lesions using whole spine magnetic resonance imaging (MRI) in AS. <h3>Methods</h3> A total of 62 patients with AS who had taken whole spine MRI were retrospectively enrolled in this study. Regional distribution in the entire spine and within the individual discovertebral unit (DVU) including the central, peripheral, and diffuse disc types of Andersson lesion was assessed. We compared the number of DVUs with Andersson lesion with clinical and radiographic indicies such as erythrocyte sediment rate (ESR), C-reactive protein (CRP), BASDAI, BASFI, and modified Stoke Ankylosing Spondylitis Spine Score (mSASSS). <h3>Results</h3> Fifty-three patients (85.5%) had at least one Andersson lesion. We found a total of 129 DVUs with Andesson lesions (9.0%) in the entire spine levels. Andersson lesion at the lower thoracic spine (from T7–8 to T12-L1) was most commonly detected than other spine levels. Among the total 151 Andersson lesions, 41 lesions were identified at the central, 26 lesions at the anterior peripheral, 44 lesions at the posterior peripheral, and 40 lesions at the diffuse disc types. However, the number of Andersson lesions did not correlate with ESR, CRP, BASDAI, BASFI, and mSASSS in AS patients (p&gt;0.05 of all). <h3>Conclusions</h3> Our study indicates that presence of Andersson lesion in AS patients is clearly underestimated. MRI provides more increased opportunity to detect earlier Andersson lesions than conventional radiography. <h3>References</h3> Park YS, Kim JH, Ryu JA, Kim TH. The Andersson lesion in ankylosing spondylitis: distinguishing between the inflammatory and traumatic subtypes. J Bone Joint Surg Br 2011;93:961–6. de Vries MK, van Drumpt AS, van Royen BJ, van Denderen JC, Manoliu RA, van der Horst-Bruinsma IE. Discovertebral (Andersson) lesions in severe ankylosing spondylitis: a study using MRI and conventional radiography. Clin Rheumatol 2010;29:1433–8. Kabasakal Y, Garrett SL, Calin A. The epidemiology of spondylodiscitis in ankylosing spondylitis - a controlled study. Br J Rheumatol 1996;35:660–3. <h3>Disclosure of Interest</h3> None declared
Future medical leaders alienated by government’s handling of NHS, peers told
Authors: Adrian O’Dowd
Journal: BMJ (2016)

Potential future medical leaders are becoming demoralised and alienated from the health service as a result of the government’s handling of the NHS in recent times, peers have been told.

Union representatives issued warnings about the level of discontent felt by doctors, nurses, and other parts of the NHS workforce during an evidence session for the House of Lords inquiry into the long term sustainability of the NHS.

During the session, held on 8 November, peers asked workforce experts and union leaders what the current key pressures were.

Mark Porter, chair of the BMA, giving evidence, said that the consequences …
Shifting Balance on a Static Mutation–Selection Landscape: A Novel Scenario of Positive Selection
Authors: Christopher T. Jones, Noor Youssef, Edward Susko, Joseph P. Bielawski
Journal: Molecular Biology and Evolution (2016)

A version of the mechanistic mutation–selection (MutSel) model that accounts for temporal dynamics at a site is presented. This is used to show that the rate ratio dN/dS at a site can be transiently >1 even when fitness coefficients are fixed or the fitness landscape is static. This occurs whenever a site drifts away from its fitness peak and is then forced back by selection, a process reminiscent of shifting balance. Shifting balance is strongest when the substitution process is not dominated by selection or drift, but admits interplay between the two. Under this condition, site-specific changes in dN/dS were inferred in 78–100% of trials, and positive selection (i.e., dN/dS>1⁠) in 10–40% of trials, when sequence alignments generated under MutSel were fitted to two popular phenomenological branch-site models. These results demonstrate that positive selection can occur without a change in fitness regime, and that this is detectable by branch-site models. In addition, MutSel is used to show that a site can be occupied by a sub-optimal amino acid for long periods on a fixed landscape when selection is stringent. This has implications for the interpretation of constant-but-different site patterns typically attributed to changes in fitness. Furthermore, a version of MutSel with episodic changes in fitness coefficients is used to illustrate systematic differences between parameters used to generate data under MutSel and their counterparts estimated by a simple codon model. Motivated by a discrepancy in the literature, interpretation of dN/dS in the context of MutSel is also discussed.
OC-006 Anti-TNF Therapy Alters Dendritic Cell Trafficking and Cytokine Production in Crohn’s Disease
Authors: PA Hendy, D Reddi, D Barnardo, L Durant, A Noble, P Bhat, N English, SC Knight, AL Hart
Journal: Gut (2016)

<h3>Introduction</h3> Dendritic cells (DC) act as a bridge between the innate and adaptive immune system, sensing and presenting antigen to lymphocytes and mounting either a tolerogenic or inflammatory response. They are able to imprint homing capacity on T-cells, directing them into specific tissues. Abnormal DC function contributes to the pathogenesis of Crohn’s disease and thus DC represent a potential therapeutic target. In this study we have investigated the effect of anti-TNFα therapy on circulating DC of patients with Crohn’s disease. <h3>Methods</h3> We recruited 13 consecutive patients with active luminal Crohn’s due to start anti-TNFα therapy. Clinical parameters including the Harvey-Bradshaw index, C-reactive protein and faecal calprotectin were measured. Peripheral blood mononuclear cells were isolated from each patient immediately before and six weeks after commencing anti-TNFα therapy. At both time points flow cytometry was performed to assess DC phenotype and function. We also analysed subsets of DC: myeloid (mDC, CD11c<sup>+</sup>CD123<sup>−</sup>) and plasmacytoid (pDC, CD11c<sup>−</sup>CD123<sup>+</sup>). Expression of phenotypic markers (including maturation and homing markers and pattern recognition receptors) and intra-cellular on-going DC cytokine production were determined. <h3>Results</h3> Treatment with anti-TNFα resulted in an alteration of the phenotype of mDC in Crohn’s disease. The gut homing phenotype of mDC in Crohn’s disease was down-regulated with anti-TNFα (CLA<sup>−</sup>β7<sup>+</sup>p = 0.0056 Fig A) whilst the non-tissue specific phenotype (CLA<sup>+</sup>β7<sup>+</sup>p = 0.0026 Fig not shown) and skin homing phenotype were up-regulated (CLA<sup>+</sup>β7<sup>− </sup>p = 0.0055 Fig B). Production of TNFα and IL-6 by mDC and pDC respectively, shown to be increased in Crohn’s disease, was significantly reduced by anti-TNFα therapy (p = 0.033 and p = 0.014 Fig C and Fig D respectively). Production of IL-10 was increased following therapy (p = 0.051). There were no changes in IL-12, IL-23 and IFN-α production. Significant improvements in clinical markers were observed following treatment. <h3>Conclusion</h3> The reversal of inflammatory DC phenotype and function by anti-TNFα further highlights the potential role this antigen presenting cell may play in the pathogenesis of Crohn’s disease. DC are a promising therapeutic target in Crohn’s because they can be modulated to express a non-gut homing phenotype and direct T cells away from the gut and promote tolerogenic effects. The increase in skin homing DC following anti-TNFα treatment may explain the high rate of skin complications. The reduction in gut homing DC may offer an explanation for reduced treatment success with vedolizumab (α4β7 blocker) after previous anti-TNFα therapy (reduction of vedolizumab treatment target). <h3>Disclosure of Interest</h3> None Declared
Imatinib and Interferon-Alpha Maintenance Therapy for Patients with Philadelphia-Positive Acute Lymphoblastic Leukemia (Ph+ALL) Ineligible for Allogeneic Stem Cell Transplantation (SCT).
Authors: Heike Pfeifer, Barbara Wassmann, Andreas Käbisch, Michael Lübbert, Lothar Leimer, Aristoteles Giagounidis, Dieter Hoelzer, Oliver G. Ottmann
Journal: Blood (2009)
CBIO-10Bcl-2 FAMILY MEMBER Mcl-1 EXPRESSION IS REDUCED UNDER HYPOXIA BY THE E3 LIGASE FBW7 CONTRIBUTING TO BNIP3 INDUCED CELL DEATH IN GLIOMA CELLS
Authors: Yongqiang Chen, Elizabeth Henson, Epsita Shome, Wenyan Xiao, David Eisenstat, Spencer Gibson
Journal: Neuro-Oncology (2015)

Mcl-1 is an anti-apoptotic Bcl-2 family member that is often over-expressed in the malignant brain tumor glioblastoma (GBM). It has been previously shown that epidermal growth factor receptors (EGFR) up-regulate Mcl-1 contributing to a cell survival response. Hypoxia is a poor prognostic marker in glioblastoma despite the fact that hypoxic regions have areas of necrosis. Hypoxic regions of GBM also highly express the pro-cell death Bcl-2 family member BNIP3, yet when BNIP3 is over-expressed in glioma cells, it induces cell death. The reasons for this discrepancy are unclear. Herein we have found that Mcl-1 expression is reduced under hypoxia due to degradation by the E3 ligase FBW7 leading to increased hypoxia induced cell death. This cell death is augmented by EGFR activation leading to increased Mcl-1 expression under hypoxia. Conversely, BNIP3 is over-expressed in hypoxia at times when Mcl-1 expression is decreased. Knocking down BNIP3 expression reduces hypoxia cell death and Mcl-1 expression effectively blocks BNIP3 induced cell death. Of significance, BNIP3 and Mcl-1 are colocalized under hypoxia in glioma cells, GBM tumors and in xenograft glioma tumors expressing the mutant EGFR (EGFRvIII). These results suggest that Mcl-1 can block the ability of BNIP3 to induce cell death under hypoxia in GBM tumors.
Randomized, split-body, single-blinded clinical trial of topical broccoli sprout extract: Assessing the feasibility of its use in keratin-based disorders
Authors: Michelle L. Kerns, Lark Guss, Jed Fahey, Bernard Cohen, Jill M.C. Hakim, Sarah Sung, Rosemary G. Lu, Pierre A. Coulombe
Journal: Journal of the American Academy of Dermatology (2016)
Age as a prognostic factor for outcome in patients (pts) with rhabdomyosarcoma (RMS)
Authors: J. C. van Gaal, W. T. van der Graaf, B. Rikhof, Q. C. van Hoesel, J. L. Loeffen, S. Sleijfer, E. S. de Bont
Journal: Journal of Clinical Oncology (2008)

10514
High-Throughput Drug Screening Identifies Pyrimethamine As a Potent and Selective Inhibitor of Acute Myeloid Leukemia
Authors: Amit Sharma, Nidhi Jyotsana, Courteney K. Lai, Anuhar Chaturvedi, Kerstin Görlich, Cecilia Murphy, Jan E. Blanchard, Arnold Ganser, Eric Brown, John A. Hassell, R. Keith Humphries, Michael A Morgan, Michael Heuser
Journal: Blood (2014)
SNP Genotypes Show Association with Common Toxicities during both VAD Induction and High Dose Melphalan with Autologous Transplant Support in Intergroup Trial S9321 for Myeloma: From the Bank on a Cure.
Authors: Brian G. Van Ness, John C. Crowley, Christine Ramos, Suzanne Grindle, Erik Rasmussen, Antje Hoering, Philip Greipp, Bart Barlogie, Brian Durie
Journal: Blood (2005)