tbuckley/cabot-search huggingface dataset:
Differences in quality of life and emotional health by diagnosis among women with early-stage gynecological cancers.
Authors: Rachel Isaksson Vogel, Patricia Jewett, Audrey Messelt, Heewon Lee, Susan Everson-Rose, Dorothy Hatsukami, Melissa Ann Geller, Deanna Gek Koon Teoh, Anne Hudson Blaes
Journal: Journal of Clinical Oncology (2019)

e23180 Background: Psychosocial outcomes have been described in women with gynecological cancers, but potential differences by diagnosis have received less attention. We sought to compare quality of life (QOL) and emotional health among early stage gynecological cancer survivors by disease location. Methods: We present baseline data from an ongoing cohort study of gynecological cancer patients treated at an academic cancer center. Measures include cancer-related QOL, emotional health and negative (post-traumatic stress disorder-PTSD) and positive (post-traumatic growth-PTG) reactions to cancer. Univariate and multivariate linear regression models (restricted to stage I or II; excluding vaginal/vulvar) explored differences in QOL and emotional health by diagnosis. Potential confounders considered for inclusion in the final models were age, stage, education, income, partner status, treatment status, and race. Results: 222 patients with early stage disease completed the survey: 56 (25.2%) ovarian, 122 (55.5) endometrial, 33 cervical (14.9%), and 11 (5%) vaginal/vulvar cancer. Cervical and vaginal/vulvar cancer patients reported greater cancer-related distress, anxiety and PTSD scores (Table). Endometrial cancer patients reported lowest PTG scores. Conclusions: Our analyses suggest early stage gynecological cancer patients face different psychosocial sequelae based on diagnosis, with worse outcomes generally being associated with younger age. Further research is needed to assess low PTG among endometrial cancer patients, since PTG is considered a potentially beneficial psychosocial outcome of cancer. [Table: see text]
Consultant who breached tribunal’s conditions and failed to remediate is struck off
Authors: Clare Dyer
Journal: BMJ (2019)

A former locum consultant in stroke medicine who breached conditions imposed on him by a medical practitioners tribunal has been struck off the UK medical register, after a new hearing found that he continued to challenge the original tribunal’s findings and the regulator’s authority.

In 2016 Joseph Nankhonya was found guilty of misconduct in treating two patients at Warrington and Halton Hospitals NHS Foundation Trust. He failed to arrange urgent brain imaging for one patient and conducted an inadequate assessment of another, the tribunal found, persisting in a wrong diagnosis after ultrasound scans contradicted it.

His conduct was originally considered …
The modern firm
Authors: Fiona Godlee
Journal: BMJ (2019)

The NHS is in the grip of a workforce crisis. Across England one in 12 posts (8%) are now vacant, reports the Nuffield Trust. This is part of a growing global shortage of healthcare workers but has its own special causes and characteristics: failure to train and retain enough home grown health professionals, failure to recruit sufficient numbers from abroad, and an unprecedented wave of trainee departures and early retirement driven by rota gaps, overwork, disillusionment and pension rules.

As Andy Cowper reported a few weeks ago (doi:10.1136/bmj.l2209), despite promises of 5000 extra GPs, we now have fewer GPs per patient …
Biomarkers and clinical characteristics of autoimmune chronic spontaneous urticaria: Results of the PURIST Study
Authors: Nicole Schoepke, Riccardo Asero, André Ellrich, Marta Ferrer, Ana Gimenez‐Arnau, Clive E. H. Grattan, Thilo Jakob, George N. Konstantinou, Ulrike Raap, Per Stahl Skov, Petra Staubach, Arno Kromminga, Ke Zhang, Carsten Bindslev‐Jensen, Alvaro Daschner, Tamar Kinaciyan, Edward F. Knol, Michael Makris, Nadine Marrouche, Peter Schmid‐Grendelmeier, Gordon Sussman, Elias Toubi, Martin K. Church, Marcus Maurer
Journal: Allergy (2019)

Abstract Background Autoimmune chronic spontaneous urticaria (aiCSU) is an important subtype of chronic spontaneous urticaria (CSU) in which functional IgG autoantibodies to IgE or its high‐affinity receptor (FcεRI) induces mast cell degranulation and subsequent symptom development. However, it has not been tightly characterized. This study aimed to better define the clinical and immunological features and to explore potential biomarkers of aiCSU. Methods This was a multinational, multicenter study of 182 CSU patients. The clinical features studied included: urticaria activity and impact (UAS7 and quality of life); autologous serum skin test (ASST); IgG anti‐FcεRI and IgG anti‐IgE; IgG‐anti‐thyroperoxidase (IgG anti‐TPO); total serum IgE; and basophil reactivity (BASO) using the basophil activation test (BAT) and basophil histamine release assay (BHRA). Results Of the 182 patients, 107 (59%) were ASST+, 46 (25%) were BASO+, and 105 (58%) were IgG anti‐FcεRI+/IgE+. Fifteen patients (8%) fulfilled all three criteria of aiCSU. aiCSU patients appeared more severe (UAS7 21 vs 9 P &lt; 0.016) but showed no other clinical or demographic differences from non‐aiCSU patients. aiCSU patients also had markedly lower total IgE levels ( P &lt; 0.0001) and higher IgG anti‐TPO levels ( P &lt; 0.001). Of biomarkers, positive BAT and BHRA tests were 69% and 88% predictive of aiCSU, respectively. Conclusions aiCSU is a relatively small but immunologically distinct subtype of CSU that cannot be identified by routine clinical parameters. Inclusion of BHRA or BAT in the diagnostic workup of CSU patients may aid identification of aiCSU patients, who may have a different prognosis and benefit from specific management.
THU0049 CORRELATION BETWEEN IL-6 AND OSTEOCALCIN SERUM LEVELS WITH DISEASE ACTIVITY IN RHEUMATOID ARTHRITIS (RA) PATIENTS
Authors: Ervin Rapushi, Teuta Backa, Artur Zoto, Ermira Zicishti, Lediana Nuhaj, Valbona Salko, Indin Xhemali
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> IL-6 plays a significant role in RA pathophysiology. It is considered nowadays as an important inflammation marker and it is responsible for a wide range of articular and extra-articular manifestations in RA patients. Osteocalcin is a protein (non collagenous) that can be found in the bones extracellular matrix, as well as in the circulating blood serum. This protein is a marker of bone formation and turnover. <h3>Objectives</h3> Evaluating IL-6 and osteocalcin serum levels in RA patients and their correlation with disease activity. <h3>Methods</h3> We examined 126 patients previously diagnosed with RA according to the ACR/EULAR 2010 criteria. To all patients it was measured the IL-6 serum level (&lt;4.0 pg/mL), and also the osteocalcin serum level using the ELISA-OSTEO kit method (13-46ng/ml) and the disease activity was defined according to the DAS28. By using this activity score index the patients were divided in three groups: group I with active disease scoring &gt; 5.1 (43 patients); group II with moderate disease activity scoring between 3.2 - 5.1 (52 patients); and group III with no disease activity scoring &lt;3.2 (31 patients). <h3>Results</h3> IL-6 serum level resulted elevated in patients group I (1.9±0.6pg/ml;) and group II (0.9±0.3pg/ml) and normal in patients group III (0.35±0.1pg/ml). Osteocalcin serum level resulted elevated in the three groups but with higher serum levels in patients group I and II (62±1.9ng/ml; 49.2±2.6ng/ml) and less higher serum levels in group III (44.5±1.7ng/ml). IL-6 serum level correlates best with osteocalcin serum level in patients group I and II (r=0.9). IL-6 serum level correlates with disease activity (r=1). Osteocalcin serum level correlates with disease activity in group I and II (r=0.9) but not with disease activity in group III (r=0.4). <h3>Conclusion</h3> There is a significant correlation between IL-6 serum level and disease activity according to DAS 28 in RA patients. The elevation of osteocalcin serum level correlates with disease activity in RA patients with high and moderate disease activity which is an important finding of the intense bone remodeling, whereas in patients with no disease activity bone remodeling tents to slow down. <h3>Disclosure of Interests</h3> None declared
AB0805 WHAT FACTORS AFFECT THE RESULT OF LONG-TERM ANALGESIC THERAPY FOR OSTEOARTHRITIS? DATA FROM A MULTICENTER OPEN STUDY OF ORAL AVOCADO/SOYBEAN UNSAPONFABLES EFFECTIVENESS
Authors: Elena Pogozheva, Andrey Karateev, Alexander Lila, Vera Amirdzhanova, Ekaterina Filatova
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Symptomatic slow-acting drugs for OA (SYSADOAs) and oral nonsteroidal anti-inflammatory drugs (NSAIDs) play a central role in the pharmacological management of osteoarthritis (OA). Factors affecting the effectiveness of OA therapy should be taken into account. Objectives: to identify factors affecting the effectiveness of long-term analgesic therapy in patients with OA. Methods: the study included 6448 patients with knee OA (mean age 57.8 ± 10.2 years, 70,9% women), with pain level ≥40 mm VAS. All patients received oral avocado/soybean unsaponfables (ASU) 300 mg/day within 3 months and ketoprofen lysine salt (KLS) 320 mg/day within 2 weeks at the beginning of the study. A 100 mm visual analog scale (VAS) was used to assess pain intensity. The result of treatment was evaluated on a scale of 0-5 points, where 0 – no effect, 5 - excellent effect. The criteria for a "good response" to therapy were: pain reduction ≥50% and treatment result ≥ 4 points. The value of the studied factors was determined using odds ratio; 95% confidence interval (OR; 95% CI). <h3>Results</h3> After 3 months of therapy the pain level decreased from 63.7 ± 12.0 mm to 14.2 ± 11.7 mm. A good response to treatment was noted in 87.4% of patients. Sex, body mass index ≥ 30 kg/m<sup>2</sup>, type 2 diabetes, poor effect of NSAIDs and SYSADOAs in history did not affect the result. The effectiveness of treatment was less in patients &gt;65 years (OR 0.418; 95% CI 0.342-0.509, p&lt;0.001), OA stage ≥ 2 by Kelgren-Lawrence (OR 0.556; 95% CI 0.298-0.738, p&lt;0.001), with rest pain (OR 0.690; 95% CI 0.596 - 0.800, p&lt;0.001), synovitis (OR 0.780; 95% CI 0.673-0.900, p=0.001), and sensory symptoms such as burning, pain cold, electric shocks (OR 0.530; 95% CI 0.458-0.613, p&lt;0.001). Conclusion: the ASU and KLS combination allows to achieve successful pain control in OA. A number of factors: age &gt;65 years, OA stage ≥ 2 by Kelgren-Lawrence, rest pain, synovitis, and sensory symptoms are associated with the worst result of treatment. <h3>Disclosure of Interests</h3> Elena Pogozheva: None declared, Andrey Karateev: None declared, Alexander Lila Speakers bureau: Pfizer, Inc., MSD, Novartis, AbbVie Inc., Celgen Corporation, Biocad, Janssen, UCB, Inc., Vera Amirdzhanova: None declared, Ekaterina Filatova: None declared
Abstract 17622: Role of SHARPIN, an Integrin Inhibitor, in Angiogenesis
Authors: Francesca Bonini, Peggy Schuster, Aikaterini Gatsiou, Konstantinos Stellos, Andreas M Zeiher, Emmanouil Chavakis
Journal: Circulation (2016)

β1-integrins are mediating endothelial cell (EC) adhesion to extracellular matrix proteins and are critical mediators of neovascularization. In addition, intracellular signaling stimulating integri...
Regulation of immunity and allergy by helminth parasites
Authors: Rick M. Maizels
Journal: Allergy (2019)

There is increasing interest in helminth parasite modulation of the immune system, both from the fundamental perspective of the "arms race" between host and parasite, and equally importantly, to understand if parasites offer new pathways to abate and control untoward immune responses in humans. This article reviews the epidemiological and experimental evidence for parasite down-regulation of host immunity and immunopathology, in allergy and other immune disorders, and recent progress towards defining the mechanisms and molecular mediators which parasites exploit in order to modulate their host. Among these are novel products that interfere with epithelial cell alarmins, dendritic cell activation, macrophage function and T-cell responsiveness through the promotion of an immunoregulatory environment. These modulatory effects assist parasites to establish and survive, while dampening immune reactivity to allergens, autoantigens and microbiome determinants.
Single-Cell RNA Sequencing of the T Helper Cell Response to House Dust Mites Defines a Distinct Gene Expression Signature in Airway Th2 Cells
Authors: Christopher Andrew Tibbitt, Julian Mario Stark, Liesbet Martens, Junjie Ma, Jeff Eron Mold, Kim Deswarte, Ganna Oliynyk, Xiaogang Feng, Bart Norbert Lambrecht, Pieter De Bleser, Susanne Nylén, Hamida Hammad, Marie Arsenian Henriksson, Yvan Saeys, Jonathan Marie Coquet
Journal: Immunity (2019)
PB1836 BURKITT LEUKEMIA/LYMPHOMA IN CHILDREN: CYTOGENETIC CHARACTERISTICS AND OUTCOME
Authors: M. Moschovi, A. Zampogiannis, N. Tourkantoni, M. Tzanoudaki, M. Kanariou, C. Kanaka
Journal: HemaSphere (2019)

Background: Burkitt Leukemia/Lymphoma (BL/L) is a rare, highly aggressive hematological malignancy. Although children diagnosed with advanced stage disease have a poorer prognosis, current therapeutic protocols achieve an overall survival rate in children of up to 90%. Cytogenetically, BL/L is characterized by the translocations t(8;14) and the variant t(8;22) and t(2;8) which juxtapose immunoglobulin sequences with the c-MYC oncogene, leading to its constitutional expression which is crucial for the BL/L pathogenesis. Aims: The aim of our study is: a) to present the clinical characteristics, the immunophenotype and the chromosomal abnormalities of BL/L patients, b) to estimate the therapeutic efficacy of the current treatment protocols. Methods: Four children, diagnosed with BL/L and treated in our center in the last decade are included in this study. Five colour FACS immunophenotype and cytogenetics were applied at diagnosis. All children were treated according to the FAB/LMB96 protocol for BL/L. All remain in follow-up. Results: The age of diagnosis ranged from 4 to 14 years (mean: 8.5yrs). The male to female ratio was 4/0, and confirmed the male preponderance that is described in the literature.The most common clinical manifestations were prolonged mild fever, fatigue and lack of appetite. One child presented with lower limb myalgia, caused by an abdominal paravertebral lymphoid mass. WBC count ranged from 6.000 to 12.000/ml for all children except one case where excessive leukocytosis, with WBC count over 85.000/ml, was observed. Lactate dehydrogenase (LDH) ranged from 3.031 to 7.075U/L (mean:5.000). All 4 patients's blasts shared the same immunophenotypic features, ie: CD45+++CD19+CD10+CD20+skappa+. Cytogenetic evaluation revealed aneuploidy in two patients, including one case with monosomy 4 and one case with heavy hyperploidy (78,XY). Immunoglobulin-MYC translocation was found in all patients, including 3 cases with the t(8;14) translocation and one case with the t(8;22) variant. In the case with the heavy hyperploidy, a double t(8;14) was observed. All patients were treated according to the FAB/LMB96 protocol, and achieved complete first remission. All remain in first complete remission, with a mean follow-up time of 4.4 years, without late effects Summary/Conclusion: Immunophenotypic features were typical for the diagnosis and did not show any variations related to cytogenetics. Cytogenetic abnormalities such as monosomy 4, heavy hyperploidy (78,XY) or a double t(8;14) that were observed in our cases had no negative impact on the outcome. Despite the small number of patients, our findings appear promising and confirm the favorable prognosis of children with BL/L. Our results confirm that FAB/LMB96 is an effective protocol for the treatment of childhood BL/L.
Deep Learning–Based Multi-Omics Integration Robustly Predicts Survival in Liver Cancer
Authors: Kumardeep Chaudhary, Olivier B. Poirion, Liangqun Lu, Lana X. Garmire
Journal: Clinical Cancer Research (2017)

Identifying robust survival subgroups of hepatocellular carcinoma (HCC) will significantly improve patient care. Currently, endeavor of integrating multi-omics data to explicitly predict HCC survival from multiple patient cohorts is lacking. To fill this gap, we present a deep learning (DL)-based model on HCC that robustly differentiates survival subpopulations of patients in six cohorts. We built the DL-based, survival-sensitive model on 360 HCC patients' data using RNA sequencing (RNA-Seq), miRNA sequencing (miRNA-Seq), and methylation data from The Cancer Genome Atlas (TCGA), which predicts prognosis as good as an alternative model where genomics and clinical data are both considered. This DL-based model provides two optimal subgroups of patients with significant survival differences (P = 7.13e-6) and good model fitness [concordance index (C-index) = 0.68]. More aggressive subtype is associated with frequent TP53 inactivation mutations, higher expression of stemness markers (KRT19 and EPCAM) and tumor marker BIRC5, and activated Wnt and Akt signaling pathways. We validated this multi-omics model on five external datasets of various omics types: LIRI-JP cohort (n = 230, C-index = 0.75), NCI cohort (n = 221, C-index = 0.67), Chinese cohort (n = 166, C-index = 0.69), E-TABM-36 cohort (n = 40, C-index = 0.77), and Hawaiian cohort (n = 27, C-index = 0.82). This is the first study to employ DL to identify multi-omics features linked to the differential survival of patients with HCC. Given its robustness over multiple cohorts, we expect this workflow to be useful at predicting HCC prognosis prediction. Clin Cancer Res; 24(6); 1248-59. ©2017 AACR.
Methicillin-resistant Staphylococcus aureus emerged long before the introduction of methicillin into clinical practice
Authors: Catriona P. Harkins, Bruno Pichon, Michel Doumith, Julian Parkhill, Henrik Westh, Alexander Tomasz, Herminia de Lencastre, Stephen D. Bentley, Angela M. Kearns, Matthew T. G. Holden
Journal: Genome biology (2017)

The spread of drug-resistant bacterial pathogens poses a major threat to global health. It is widely recognised that the widespread use of antibiotics has generated selective pressures that have driven the emergence of resistant strains. Methicillin-resistant Staphylococcus aureus (MRSA) was first observed in 1960, less than one year after the introduction of this second generation beta-lactam antibiotic into clinical practice. Epidemiological evidence has always suggested that resistance arose around this period, when the mecA gene encoding methicillin resistance carried on an SCCmec element, was horizontally transferred to an intrinsically sensitive strain of S. aureus.Whole genome sequencing a collection of the first MRSA isolates allows us to reconstruct the evolutionary history of the archetypal MRSA. We apply Bayesian phylogenetic reconstruction to infer the time point at which this early MRSA lineage arose and when SCCmec was acquired. MRSA emerged in the mid-1940s, following the acquisition of an ancestral type I SCCmec element, some 14 years before the first therapeutic use of methicillin.Methicillin use was not the original driving factor in the evolution of MRSA as previously thought. Rather it was the widespread use of first generation beta-lactams such as penicillin in the years prior to the introduction of methicillin, which selected for S. aureus strains carrying the mecA determinant. Crucially this highlights how new drugs, introduced to circumvent known resistance mechanisms, can be rendered ineffective by unrecognised adaptations in the bacterial population due to the historic selective landscape created by the widespread use of other antibiotics.
SP0140 HOT: MANAGEMENT OF JUVENILE IDIOPATHIC ARTHRITIS 2019 AND BEYOND
Authors: Michael Beresford
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Improvements in our care and understanding of paediatric rheumatic disorders has undergone tremendous advances in the last decade. The transformative therapeutic armamentarium now available in targeting treatments for juvenile idiopathic arthritis (JIA) combined with a step change in addressing a holistic approach to our multi-disciplinary management of children and young people, seeks to make a real difference to the lives of the patients we care for. <h3>Objectives:</h3> To provide an overview on best management of juvenile idiopathic arthritis, an outlook for new treatment possibilities and JIA outcome with a focus on adults. <h3>Methods:</h3> The advances in our understanding of disease mechanisms, coupled with legislative changes across the EU and North America have led to an increase in clinical trials and evidence based new therapies for children with JIA. This progress continues to accelerate, fostered by major international collaborative efforts in clinical and translational research, and stratified/personalised medicine. Our greater understanding of the genetic, molecular and mechanistic pathways underpinning JIA in children, in whom there is less accumulation of significant co-morbidities and organ damage, have offered new opportunities for this advancement. <h3>Results:</h3> The shared knowledge between paediatric and adult clinical research communities and international collaboration has ensured the management of JIA has been transformed. However, we must not be complacent. Future progress will depend upon ensuring that appropriate clinical trials, using methodology and trial design appropriate for and including the insights and perspectives of children and young people care carried out in paediatric rheumatology. This is especially important with the advent of newer molecules and therapies that are relevant to our patients and clinicians treating them, and not just in meeting regulatory requirements. <h3>Conclusion:</h3> As the management of JIA continues to evolve and develop, equitable access to the very best care and new and effective treatments and therapies is critical across the world. <h3>Disclosure of Interests:</h3> None declared