tbuckley/cabot-search huggingface dataset:
AB0064 Expression of Chemokines and Chemokine Receptors on Peripheral Blood Mononuclear Cells of Patients with Rheumatoid Arthritis
Authors: Z. Jajic, A. Sucur, T. Kelava, M. Artukovic, A. Stipic-Markovic, S. Ivcevic, F. Grubišić, D. Flegar, N. Kovačić, V. Katavic, D. Grcevic
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> Rheumatoid arthritis (RA) is characterized by chronic inflammatory response as well as enhanced bone destruction. Development of bone erosions is critically dependent on osteoclasts, which are highly specialized bone cells capable of resorbing the mineralized matrix. Osteoclast progenitors (OCPs), contained among myeloid hematopoietic lineage, could be found in the peripheral blood and synovial tissue of patients with RA, mediating bone loss locally, in the form of bone erosions and joint osteolysis, and systemically, with loss of skeletal bone density. <h3>Objectives</h3> To define these chemotactic signals by analyzing expression of several chemokines and chemokine receptors on T lymphocytes and OCPs in the peripheral blood of RA patients, to measure the levels of their respective ligands in serum and synovial fluid of RA patients, and to assess the osteoclastogenic potential of OCPs. <h3>Methods</h3> Mononuclear cells were isolated from peripheral blood of healthy controls and RA patients. The phenotype of isolated mononuclear cells was determined using flow cytometry. OCPs (CD3-CD19-CD56-CD11b+CD14+) were analyzed for the expression of the following chemokine receptors: C5AR1, CCR1, CCR2, CCR4, CXCR4. T lymphocytes (CD3+CD4+ or CD3+CD8+) were analyzed for expression of CXCR5, CCR4, CCR6 chemokine receptors. Chemokine ligand concentrations (MIP-1α/CCL3, MIP-1β/CCL4, MCP-1/CCL2, RANTES/CCL5) were measured in serum and synovial fluid of RA patients using flow cytometry bead based array. OCPs were sorted and plated into cell culture with M-CSF and RANKL. After two weeks, the cells were stained for TRAP enzyme and positive, mature, osteoclasts were counted. <h3>Results</h3> Human peripheral blood OCPs similarly expressed chemokine receptors CCR1, CCR2, CCR4 and CXCR4 in RA and healthy subjects. However, MCP1/CCL2, MIP1a/CCL3 and MIP1b/CCL4 concentrations were significantly higher in synovial fluid (and blood for CCL2 and CCL4). Cell culture revealed no significant differences in mature osteoclast count between RA and control group. The proportion of T lymphocytes expressing CCR4 was two-fold higher in RA patients compared to controls. T lymphocyte expression of CXCR5 and CCR6 was similar between RA and control group. <h3>Conclusions</h3> Although OCPs in RA have a differentiation potential similar to controls, levels of several chemokines are upregulated, indicating a possible chemotactic mechanism of OCP migration to affected joints. These results may help to reveal migration mechanism of T lymphocytes and OCPs specifically associated with RA in order to develop more efficient therapeutic approaches. <h3>Acknowledgements</h3> This work has been supported by Croatian Science Foundation (project number 5699). <h3>Disclosure of Interest</h3> None declared
THU0452 The Relationship Between 3D MRI Knee Bone Shape and Prevalent and Incident Knee Pain: Data from the Osteoarthritis Initiative: Table 1.
Authors: A. Barr, B. Dube, E. Hensor, S. Kingsbury, G. Peat, L. Sharples, M. Bowes, P.G. Conaghan
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> Incident frequent knee symptoms may represent early knee OA. MRI-detected OA bone pathology is associated with prevalent frequent knee OA symptoms (PFKS) and incident frequent knee OA symptoms (IFKS) in pre-radiographic knee OA. Active appearance modelling (AAM) enables accurate, 3D quantification of MRIs. Changes in 3D subchondral bone shape derived from AAMs are predictive of incident radiographic knee OA. However, the association of 3D subchondral bone shape with onset of knee symptoms is unknown. <h3>Objectives</h3> To determine the relationship between scalar 3D bone shape and PFKS and IFKS in individuals at increased risk of knee OA. <h3>Methods</h3> AAMs of the femur, tibia and patella and linear discriminant analysis identified vectors best classifying knees having OA vs. no OA. Vectors were scaled such that -1 and +1 represented the mean non-OA and mean OA shapes, respectively. Using a subcohort of 1114 persons with Kellgren Lawrence (KL) zero in both knees at the 12 month visit from the osteoarthritis initiative (OAI) we assessed whether 3D bone shape vector was associated with PFKS or IFKS. We defined PFKS as (pain, aching or stiffness) or medication use for knee symptoms most days of 1 month in the past 12 months. IFKS was defined as those lacking PFKS at baseline but reporting PFKS at any two consecutive annual OAI visits between the 12 and 60-month visits. Logistic regression, using one knee per individual, was used to evaluate the association between 3D bone shape vectors of the femur, tibia and patella and each of PFKS at the 12 month visit and IFKS. All models were adjusted for age, sex, BMI, previous knee injury and previous surgery. <h3>Results</h3> The 3D bone shape vectors of the femur, tibia and patella were not associated with PFKS in the univariable models at the 12 month visit. Adjusted odds ratios (95% CI) for the femur, tibia and patella were; 1.00 (0.71, 1.26), 1.12 (0.90, 1.41), 0.84 (0.66, 1.08) respectively, all p&gt;0.05. The 3D bone shape vector was significantly associated with IFKS in the univariable model for the tibia only. The 3D bone shape vectors of the femur, tibia and patella were not associated with IFKS after adjustment for covariates (Table 1). However BMI, previous knee surgery and knee injury were significantly associated with PFKS and IFKS. <h3>Conclusions</h3> 3D bone shape is not associated with prevalent or incident frequent knee pain in individuals without radiographic OA but at increased risk of knee OA. <h3>Disclosure of Interest</h3> None declared
FRI0327 Febuxostat Appears Effective and Safe in Gout Patients with Severe Chronic Kidney Disease:
Authors: N. Quilis, S. Gil, M. Andrés, P. Vela, E. Pascual
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> Febuxostat is a novel nonpurine selective inhibitor of xanthine oxidase. Its predominant hepatic metabolism is an advantage for patients with gout and chronic kidney disease (CKD), so no dose adjustment is needed. However, in clinical trials patients with severe CKD were excluded [1], so caution is advised in patients with a reduced estimated glomerular filtration rate (eGFR&lt;30mL/min/1.73m<sup>2</sup>) [2]. <h3>Objectives</h3> To review our experience with febuxostat in patients with gout, and to assess outcomes in the subgroup with eGFR&lt;30mL/min/1.73m<sup>2</sup>. <h3>Methods</h3> Retrospective review. Clinical records of patients with crystal-proven gout treated with febuxostat (prescribed by a rheumatologist of the unit) were selected. Epidemiological, clinical and laboratory data were collected. Study variables were: a) the change in serum uric acid (SUA) levels after treatment with febuxostat; and b) the percentage of patients who attained SUA&lt;6mg/dL; SUA&lt;5mg/dL; and SUA&lt;4mg/dL. Two time-points were determined: 1) first lab tests after starting febuxostat, and 2) 6 months after continuous treatment with febuxostat at its maximal dose used. Comparisons according to the eGFR value (above or below 30mL/min/1.73m<sup>2</sup>) at the start of febuxostat were performed using chi-square and Mann-Whitney9s U tests. <h3>Results</h3> Records from 55 patients with gout treated with febuxostat were reviewed, mean (p25-75) aged 73 years (63-84), being 70.9% men. Gout was tophaceous in 15 patients (27.3%). The maximal dose used of febuxostat was 80 mg/d in 68,5% of patients. Other urate lowering agent had been used in 38 patients (69.1%), being skin reactions the main reason for discontinuation (11 patients, 20%). In 14 patients (25.5%) febuxostat was started at a eGFR&lt;30mL/min/1.73m<sup>2</sup>, but in no case it was below 15mL/min. The table shows the outcomes comparison regarding the eGFR values. SUA at baseline was found similar. No differences were found in the magnitude of SUA reduction after long-term febuxostat nor in the achievement of the different SUA endpoints. Variation in eGFR values was similar in both groups. Regarding safety concerns, in 11 patients febuxostat was discontinued (3 cases due to skin reactions, in one case also previously with allopurinol), but it did not differ regarding eGFR subgroups (p=0.33). <h3>Conclusions</h3> Febuxostat appears effective and safe in patients with severe renal impairment (eGFR&lt;30mL/min/1.73m<sup>2</sup>) and merit considering its use until these results are confirmed by prospective controlled studies. <h3>References</h3> Arthritis Rheum. 59:1540. Adenuric® label, EMA. <h3>Disclosure of Interest</h3> N. Quilis: None declared, S. Gil: None declared, M. Andrés: None declared, P. Vela: None declared, E. Pascual Consultant for: Menarini
COPD treatment: about collateral channels and collapsing airways
Authors: Ralf-Harto Hubner, Dominik Herzog
Journal: European Respiratory Journal (2016)

Collateral channels inside the human lungs? This phenomenon, first described by Kohn [1] in 1893, is the subject of recent investigations in the field of endoscopic lung volume reduction (ELVR) for the treatment of severe chronic obstructive pulmonary disease (COPD). ELVR with valves is a new and promising therapeutic option for irreversibly damaged emphysematous lungs. The aim of the therapy is the complete occlusion of a lobe, with endobronchial one-way valves delivered through a bronchoscope to intentionally induce a targeted atelectasis of the most damaged lobe. Many studies have described improvements in lung function, quality of life and exercise capacity in a subset of severe COPD patients, where interlobar collateral ventilation was an exclusion criterion for valve treatment [2–8]. Interlobar collateral ventilation is defined as the ventilation of alveolar structures through passages or channels that bypass the normal airways, and includes the interalveolar pores of Kohn, the bronchiole–alveolar communications of Lambert and the interbronchiolar pathways of Martin [9–14]. Collateral ventilation is present not only in COPD lungs, but also in healthy lungs [15]. The physiological function of the collateral channels is still unknown; in COPD patients they might provide channels of low resistance to better ventilate less emphysematous lung segments. The importance of collateral ventilation was ignored for over a century, but now, with their role in ELVR and the development of new bronchoscopic techniques, the study of these little channels has gained enormously in importance. Dynamic airway collapse during Chartis doesn’t identify the presence of collateral channels in that specific lobe <http://ow.ly/YGV0G>
AB0032 In-Depth Characterization of Cd24Highcd38High Transitional Human B Cells Reveals Different Regulatory Profiles and Are Abnormally Distributed in Autoimmune Diseases
Authors: Q. Simon, J.-O. Pers, D. Cornec, M.A. Rizgar, S. Hillion
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> CD24<sup>high</sup> CD38<sup>high</sup> transitional B cells represent a key stage in the developmental pathway of B cell peripheral tolerance and functional maturation. These B cells have been widely ascribed regulatory functions. However, the phenotypic and functional overlap between these cells and regulatory B cells remains controversial. <h3>Objectives</h3> In this study, we use multi-color flow cytometry with bioinformatic analyses and functional studies to show that CD24high CD38high B cells can be differentiated into multiple subsets. <h3>Results</h3> The study also reveals for the first time that human transitional B cells encompass transitional type 1 (T1) and T2 B cells but also distinct anergic T3 B cells as well as IL-10-producing CD27+ transitional B cells. Interestingly, the latter two subsets differentially regulate CD4+ T cell proliferation and polarization towards Th1 effector cells. Additional analyses show that the percentage of T3 B cells is reduced while the frequency of CD27+ transitional B cells is increased in patients with autoimmune diseases compared with matched healthy individuals. <h3>Conclusions</h3> This study provides evidence for the existence of different transitional B cell subsets each displaying unique phenotypic and regulatory functional profiles.Furthermore, the study indicates that altered distribution of transitional B cells subsets highlights different regulatory defects in autoimmune diseases. <h3>Disclosure of Interest</h3> None declared
Cutaneous Squamous-Cell Carcinoma
Authors: L Cerroni
Journal: New England Journal of Medicine (2001)

HAX-1 is an anti-apoptotic factor and overexpressed in many types of cancers.However, the functional role of HAX-1 in human cutaneous squamous cell carcinoma (cSCC) remains unclear.Our aim was to investigate the expression of HAX-1 in cSCC and its relationship with the development of cSCC.HAX-1 expression in cSCC tissues and in-vitro cell models were evaluated by real-time quantitative PCR (RT-qPCR), Western blot and immunohistochemistry.And the RNAi strategy was used to observe the relationship of HAX-1 and cSCC in A431 cells.The mRNA and protein level of HAX-1 were significantly higher in cSCC compared with normal tissue.There were significant differences in thickness (P=0.014),differentiation (P=0.027) and TNM stages (P=0.007).After knockdown the expression of HAX-1 by siRNA, the proliferation and the motility of A431 cell was inhibited obviously, and the apoptosis of A431 cells were induced too.HAX-1 may be a risk factor for patients with cSCC.As a potential tumor promoter in cSCC, HAX-1 may be a novel potential therapeutic target for cSCC treatment and deserves further investigation.
The Infant Seat as Treatment for Gastroesophageal Reflux
Authors: K Atkinson, J Biggs, P Darveniza, J Boland, A Concannon, A Dodds
Journal: New England Journal of Medicine (1984)

Five of 64 recipients of HLA-identical sibling marrow allografts who were given cyclosporin (CSP) to minimize graft-versus-host disease posttransplant had a serious neurological illness thought to be due to CSP. Characteristic clinical features included a motor spinal cord syndrome, a cerebellar-like syndrome, and mental confusion. All five recovered when the CSP dose was reduced or the drug was stopped.
Frostbite
Authors: Janet M. Torpy, Cassio Lynm, Robert M. Golub
Journal: JAMA (2011)

FrostbiteH ypothermia develops when the body temperature falls below what is needed for proper bodily functions.When a part of the body, such as an arm, hand, foot, or leg, has tissue damage from being exposed to cold weather or water, this is called frostbite.Hypothermia and frostbite are medical emergencies.Frostbite can lead to gangrene and loss of the affected body part.It is important to prevent hypothermia and frostbite by taking precautions when the weather is cold.
Solitary Retroperitoneal Metastasis as the Initial Site of the Relapse of Osteosarcoma Revealed by FDG PET/CT
Authors: Bin Liu, Hua Yang, Sabah Servaes, Hongming Zhuang
Journal: Clinical Nuclear Medicine (2015)

Adjuvant and neoadjuvant chemotherapy has altered the metastatic pattern of osteosarcoma. Overwhelming majority of the metastases from osteosarcoma are to the lungs and to the bones. Uncommon metastases to other sites can occur but usually accompany pulmonary and skeletal metastases. Here, we describe an asymptotic 14-year-old boy with solitary retroperitoneal metastasis as the initial relapse of osteosarcoma revealed by FDG PET/CT.
No Linkage between HLA and Congenital Adrenal Hyperplasia Due to 11-β-Hydroxylase Deficiency
Authors: C Brautbar, A Rösler, H Landau, I Cohen, D Nelken, T Cohen, C Levine, J Sack, A Benderli, S Moses, E Lieberman, B Dupont, L S Levine, M I New
Journal: New England Journal of Medicine (1979)
Risk Factors Associated With Early vs Delayed Dementia After Intracerebral Hemorrhage
Authors: Alessandro Biffi, Destiny Bailey, Christopher D. Anderson, Alison M. Ayres, Edip M. Gurol, Steven M. Greenberg, Jonathan Rosand, Anand Viswanathan
Journal: JAMA Neurology (2016)

Patients who have experienced intracerebral hemorrhage (ICH) appear to develop cognitive impairment at high rates, both early after ICH and over the long term.To identify and compare risk factors for early and delayed dementia after ICH.A longitudinal study enrolled patients who had experienced ICH from January 1, 2006, to December 31, 2013. A total of 738 participants 18 years or older, without pre-ICH dementia, who presented to a tertiary care academic institution with primary ICH were included in the analyses of early post-ICH dementia (EPID). After accounting for incident dementia and mortality at 6 months, 435 participants were included in the analyses of delayed post-ICH dementia (DPID).Intracerebral hemorrhage.Cognitive performance was captured using the modified Telephone Interview for Cognitive Status test. Outcomes included EPID, diagnosed within 6 months after ICH, and DPID, diagnosed beyond 6 months after ICH.Among 738 patients who had experienced ICH (mean [SD] age, 74.3 [12.1] years; 384 men [52.0%]), 140 (19.0%) developed dementia within 6 months. A total of 435 patients without dementia at 6 months were followed up longitudinally (median follow-up, 47.4 months; interquartile range, 43.4-52.1 months), with an estimated yearly incidence of dementia of 5.8% (95% CI, 5.1%-7.0%). Larger hematoma size (hazard ratio [HR], 1.47 per 10-mL increase; 95% CI, 1.09-1.97; P < .001 for heterogeneity) and lobar location of ICH (HR, 2.04; 95% CI, 1.06-3.91; P = .02 for heterogeneity) were associated with EPID but not with DPID. Educational level (HR, 0.60; 95% CI, 0.40-0.89; P < .001 for heterogeneity), incident mood symptoms (HR, 1.29; 95% CI, 1.02-1.63; P = .01 for heterogeneity), and white matter disease as defined via computed tomography (HR, 1.70; 95% CI, 1.07-2.71; P = .04 for heterogeneity) were associated with DPID but not EPID.Incident dementia early after ICH is strongly associated with hematoma size and location. Delayed incident dementia is frequent among patients who have experienced ICH and is not prominently associated with acute characteristics of ICH. These findings suggest the existence of heterogeneous biological mechanisms accounting for early vs delayed cognitive decline among patients who have experienced ICH.
Treatment of osteoporosis.
Authors: T Miazgowski, S Czekalski
Journal: BMJ (1978)

ConclisionIn the years since the second world war there has been a steady increase in sexual crimes of all kinds.Sexual assaults on children are frequent, though in many cases they amount to little more than fondling or handling the victim.Violent assaults on small girls and small boys are often by people with disordered minds.It is not within the scope of this article to discuss the nature of sexual offenders or their treatment, but deeper study of the type of people who commit sexual offences and of the best way of dealing with them is undoubtedly needed.For further reading I would refer readers to the following sources of information which were of assistance to me in preparing this
A diagnostic model for chronic hypersensitivity pneumonitis
Authors: Kerri A Johannson, Brett M Elicker, Eric Vittinghoff, Deborah Assayag, Kaïssa de Boer, Jeffrey A Golden, Kirk D Jones, Talmadge E King, Laura L Koth, Joyce S Lee, Brett Ley, Paul J Wolters, Harold R Collard
Journal: Thorax (2016)

The objective of this study was to develop a diagnostic model that allows for a highly specific diagnosis of chronic hypersensitivity pneumonitis using clinical and radiological variables alone. Chronic hypersensitivity pneumonitis and other interstitial lung disease cases were retrospectively identified from a longitudinal database. High-resolution CT scans were blindly scored for radiographic features (eg, ground-glass opacity, mosaic perfusion) as well as the radiologist's diagnostic impression. Candidate models were developed then evaluated using clinical and radiographic variables and assessed by the cross-validated C-statistic. Forty-four chronic hypersensitivity pneumonitis and eighty other interstitial lung disease cases were identified. Two models were selected based on their statistical performance, clinical applicability and face validity. Key model variables included age, down feather and/or bird exposure, radiographic presence of ground-glass opacity and mosaic perfusion and moderate or high confidence in the radiographic impression of chronic hypersensitivity pneumonitis. Models were internally validated with good performance, and cut-off values were established that resulted in high specificity for a diagnosis of chronic hypersensitivity pneumonitis.
Evaluation of syndromic surveillance in the Netherlands: its added value and recommendations for implementation
Authors: C C van den Wijngaard, W van Pelt, N J Nagelkerke, M Kretzschmar, M P Koopmans
Journal: Eurosurveillance (2011)

In the last decade, syndromic surveillance has increasingly been used worldwide for detecting increases or outbreaks of infectious diseases that might be missed by surveillance based on laboratory diagnoses and notifications by clinicians alone. There is, however, an ongoing debate about the feasibility of syndromic surveillance and its potential added value. Here we present our perspective on syndromic surveillance, based on the results of a retrospective analysis of syndromic data from six Dutch healthcare registries, covering 1999–2009 or part of this period. These registries had been designed for other purposes, but were evaluated for their potential use in signalling infectious disease dynamics and outbreaks. Our results show that syndromic surveillance clearly has added value in revealing the blind spots of traditional surveillance, in particular by detecting unusual, local outbreaks independently of diagnoses of specific pathogens, and by monitoring disease burden and virulence shifts of common pathogens. Therefore we recommend the use of syndromic surveillance for these applications.
The prediction of major depression in women: toward an integrated etiologic model
Authors: K S Kendler, R C Kessler, M C Neale, A C Heath, L J Eaves
Journal: American Journal of Psychiatry (1993)

The authors develop an exploratory, integrated etiologic model for the prediction of episodes of major depression in an epidemiologic sample of women.Both members of 680 female-female twin pairs of known zygosity from a population-based register were assessed three times at greater than 1-year intervals. The last two assessments included a structured interview evaluation for presence of episodes of major depression, defined by DSM-III-R, in the preceding year. The final structural equation model contained nine predictor variables: genetic factors, parental warmth, childhood parental loss, lifetime traumas, neuroticism, social support, past depressive episodes, recent difficulties, and recent stressful life events.The best-fitting model predicted 50.1% of the variance in the liability to major depression. The strongest predictors of this liability were, in descending order, 1) stressful life events, 2) genetic factors, 3) previous history of major depression, and 4) neuroticism. While 60% of the effect of genetic factors on the liability to major depression was direct, the remaining 40% was indirect and mediated largely by a history of prior depressive episodes, stressful life events, lifetime traumas, and neuroticism. The model suggested that at least four major and interacting risk factor domains are needed to understand the etiology of major depression: traumatic experiences, genetic factors, temperament, and interpersonal relations.Major depression is a multifactorial disorder, and understanding its etiology will require the rigorous integration of genetic, temperamental, and environmental risk factors.