tbuckley/cabot-search huggingface dataset:
Enthusiasm for prescriptive clinical prediction rules (eg, back pain and more): a quick word of caution
Authors: Robin Haskins, Chad Cook
Journal: British Journal of Sports Medicine (2016)

Prescriptive clinical prediction rules (CPRs) are commonly used in rehabilitation practice. Multiple systematic reviews have noted concern about the value of these rules and the violations of these tools. More recently, additional concerns have been outlined involving modelling errors, poor precision and fragility of the rules. This editorial outlines updated concerns about prescriptive clinical predication rules.

CPRs use baseline criteria called treatment effect modifiers,1 which are gathered from a physical examination to inform the type of treatment that a patient should preferentially receive. Many CPRs exist and have been enthusiastically incorporated in clinical practice. For example, CPRs exist to help identify which patients with back pain should receive spinal manipulation and stabilisation exercises. Their purpose is to better match patients to treatments, based on their predicted responsiveness to that treatment, independent of a diagnosis. Prescriptive CPRs are mentioned in clinical practice guidelines2 for patients with spinal pain and the premise …
SP0114 What’s New: Psoriatic Arthritis
Authors: J. J. Gomez-Reino
Journal: Annals of the Rheumatic Diseases (2013)

<h3></h3> Recent information suggests that auto-inflammatory and immune-mediated mechanisms participate in the pathogenesis of psoriatic arthritis (PsA). The synovial vascular proliferation, an unique genetic association, and the characteristic bone MRI imaging are different from rheumatoid arthritis. Also, obesity has emerged as a strong risk factor for the development of this arthritis. Interesting, obesity relates to the metabolic syndrome characterized by hypertension, insulin resistance and hypercholesterolemia, common in PsA. Researchers have demonstrated that CASPAR criteria perform well in diagnosis of early PsA. In addition, the Psoriasis Epidemiology Screening Trial questionnaire, the Toronto Psoriatic Arthritis Screening questionnaire and the EARP questionnaire are helpful for the diagnosis of PsA patients with or without psoriasis. A recent metaanalysis has revealed that infliximab, adalimumab, etanercept and golimumab are equally effective are equally effective and better than placebo in achieving ACR 20/50/70 and PsA Response Criteria, and PASi50. The new small molecule apremilast a phosphodiesterase4 (PDE4) inhibitor is also effective in achieving significant skin and joint improvement Large prospective studies and population-based studies have produced conflicting data regarding survival of PsA patients. Nevertheless, subclinical atherosclerosis and increased in the rate of cardiovascular risk factors suggest that cardiovascular events may be significant comorbidity in patients suffering from PsA <h3>Disclosure of Interest</h3> J. Gomez-Reino Grant/research support from: UCB, MSD, Consultant for: BMS, MSD, Pfize, Roche, UCB, Paid instructor for: Abbott, GSK, BMS, MSD, Pfize, Roche, UCB,
Abstract 3814: Combination of selective modular of the glucocorticoid receptor (SEGRA) with proteasome inhibitors as a novel strategy for chemotherapy of hematologic malignancies
Authors: Marianna G. Yakubovskaya, Ekaterina A. Lesovaya, Alexander Yemelyanov, Kirill I. Kirsanov, Irina Budunova
Journal: Cancer Research (2012)

Abstract Glucocorticoids are widely used for the treatment of hematological malignancies; however chronic treatment with steroids results in numerous adverse effects. Glucocorticoid receptor (GR) regulates gene expression via transactivation that requires GR homodimer binding to gene promoters; and transrepression mediated via negative interaction between GR and other transcription factors. GR transactivation is linked to metabolic side effects, while GR transrepression underlies glucocorticoid therapeutic action. One of the novel GR modulators is 2-(4-acetoxyphenyl)-2-chloro-N-methylethylammonium-chloride also called CpdA. CpdA is a synthetic analogue of a aziridine precursor isolated from the Namibian shrub Salsola tuberculatiformis Botschantzev. Using representative human T cell (CEM) and B cell (NCEB) lymphoma cell lines expressing functional GR, and their counterparts with blocked GR expression, we showed that CpdA indeed acted as dissociated GR ligand, and inhibited growth and survival of these cells via GR. Sensitivity to therapeutic effects of GCs directly depends on the amount of functional GR. The 26S protesome controls GR protein stability, and is responsible for desensitization to GCs via hormone-induced GR degradation and following development of glucocorticoid resistance in patients. Thus, the use of proteasome inhibitors represents a pharmacological approach to prevent GR down-regulation and to elevate the level of GR in cells. Proteasome inhibitor Bortezomib (BZ) was approved by FDA for the treatment of patients with multiple myeloma and mantle cell lymphoma. Since proteasome inhibitors stabilize GR, we hypothesized that BZ will augment CpdA effects as a selective GR modulator and enhance its chemotherapeutic activity. We showed that pretreatment of CEM and NCEB cells with proteasome inhibitor Bortezomib resulted in GR accumulation, and enhanced CpdA ligand properties further shifting GR activity towards transrepression evaluated by inhibiton of NF-kB and AP-1 factors. We also revealed remarkable GR-dependent synergy between CpdA and BZ in suppressing growth and survival of T and B lymphoma cells. Overall, our data provide the rationale for novel GR-based therapy for lymphoma and leukemia based on the combination of non-steroidal GR modulators with proteasome inhibitors. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3814. doi:1538-7445.AM2012-3814
BI-16 * CIRCULATING PROTEIN ANALYSIS OF POTENTIAL BRAIN TUMOR BIOMARKERS
Authors: R. Lange, A. Everett, P. Dulloor, F. K. Korley, C. Bettegowda, C. Blair, S. A. Grossman, M. Holdhoff
Journal: Neuro-Oncology (2014)

BACKGROUND: Blood-based, circulating biomarkers play an important role in the detection and care for many cancer types. Such a biomarker is not clinically available for gliomas, even though there is pressing need for improved assessment of disease response and progression. The objective of this study was to explore eight potential biomarkers in their ability to discriminate among glioblastomas (WHO Grade IV), low grade gliomas (WHO Grade II), and healthy controls. METHODS: We collected pre-operative plasma from 34 patients with gliomas (WHO grade IV, n = 23; WHO grade II, n = 11), and we collected plasma from healthy subjects as controls (n = 15). Using enzyme-linked immunosorbent assays, we measured plasma concentrations of glial fibrillary acidic protein (GFAP), neurogranin, brain derived neurotrophic factor (BDNF), intracellular adhesion molecule 5 (ICAM-5), metallothionein-3 (MT3), beta-synuclein, S100B, and neuron specific enolase (NSE). RESULTS: The distributions of plasma protein concentrations demonstrated a high degree of overlap among WHO grade IV, WHO grade II, and healthy subjects. We found statistically significant differences between WHO grade IV tumors and healthy controls for ICAM-5 (p < 0.05, increased in grade IV) and BDNF (p < 0.05 decreased in grade IV), however not for the other markers tested. Whether blood was collected pre- or post-anesthesia affected some protein levels significantly (p < 0.05). We noticed that gliosarcomas (WHO Grade IV, n = 2) had substantially elevated levels of several biomarkers compared to glioblastomas and healthy subjects. CONCLUSIONS: Our analysis concludes that the eight circulating proteins are not glioma-specific biomarkers. Anesthesia may have an effect on plasma protein levels in plasma that future circulating biomarker studies should take into account. Gliosarcomas were under-represented in our sample, but they appear to have markedly higher levels of some of the studied proteins which deserves further evaluation.
THU0168 How Low Should You Go? Towards Personalized Treatment Targets for Disease Activity in RA
Authors: Y. M. R. De Punder, T. L. Jansen, A. E. van Ede, A. A. den Broeder, P. L. van Riel, J. Fransen
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Prevention of joint damage is a main goal of treatment in Rheumatoid Arthritis (RA). However, not all patients have the same risk for joint damage during the course of disease. This is partly dependent on the level of disease activity over time, but also on three main prognostic factors at baseline: presence of anti-CCP, elevated ESR and presence of erosions. Therefore, in establishing a treatment target to prevent joint damage, the presence of these risk factors may be taken into account. A differentiation can be made in the one-size-fits-all treatment target of clinical remission and individualized treatment targets can be defined. <h3>Objectives</h3> To define DAS treatment targets for the prevention of joint damage for four different baseline risk profiles, based on the presence of anti-CCP, increased ESR and erosions. <h3>Methods</h3> Data were used from year 0 to 3 of patients of the Nijmegen Early RA cohort. Presence or absence of the three main prognostic factors anti-CCP, high ESR and erosions at baseline was combined in an individual risk profile, with a risk score of 0 to 3, representing the number of risk factors. Joint damage progression was assessed with the Ratingen score at 0 and 3 years and the Disease Activity Score (DAS) was calculated every 3 months. Logistic regression models were used for analyses. Based on the probability for joint damage progression after 3 years, treatment targets were defined for each risk profile. A probability cut point of &lt;=0.30 was considered an acceptable risk for progressive joint damage. <h3>Results</h3> An increasing number of risk factors, as well as an increasing level of DAS over time resulted in a higher probability for joint damage progression after three years. The combination of these two associations showed that a higher baseline risk score corresponded with a lower acceptable level of disease activity for the same probability for joint damage progression. Table 1 shows the treatment targets for each risk profile, based on the cut point for acceptable probability of &lt;=0.30. <h3>Conclusions</h3> Personalized risk profiles can be translated to personalized DAS treatment targets. Personalized risk profiles can be defined, based on presence of the three main baseline prognostic factors for joint damage in RA: anti-CCP, high ESR and erosions. The probability for joint damage is higher for patients with a higher risk profile. The higher the risk profile, the lower the acceptable level of disease activity to prevent joint damage. <h3>Disclosure of Interest</h3> None Declared
Observations on the Management of Hypertension by the Kempner Rice Diet
Authors: Charles R. Williamson
Journal: New England Journal of Medicine (1950)

KEMPNER'S1 2 3 4 reports of the therapeutic value of a rice and fruit diet in hypertension led to a renewed interest in the dietary treatment of this disorder. Further investigations of the Kempner regimen by other workers have not resulted in any general agreement regarding the beneficial effects.5 6 7 8 9 10 The present study has been carried out in an effort to evaluate the effects and possible mechanism of action of the Kempner rice diet.The great variability of both normal and elevated blood pressures is well known. It is evident, therefore, that in order to establish a particular procedure as responsible for a change . . .
Conjunctival Lymphoma Can Be Detected by FDG PET
Authors: Toshihiko Matsuo, Kouichi Ichimura, Takehiro Tanaka, Mitsumasa Kaji
Journal: Clinical Nuclear Medicine (2012)

Four consecutive patients presented with extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) in the conjunctiva. After the initial resection, long-term follow-up without additional therapy showed the clinical relapse. Fluorodeoxyglucose positron emission tomography fused with computed tomography (PET/CT) showed abnormal uptake in the conjunctival relapsed lesions, which were, on reresection, again proven as MALT lymphoma. Small and thin lesions of MALT lymphoma in the conjunctiva can be detected by fluorodeoxyglucose PET/CT. The resolution of PET/CT, delineated in this study, could be applied to the other areas of the body to achieve more accurate staging of lymphoma.
Presuming placeholders are relevant enables conceptual change
Authors: Christophe Heintz
Journal: Behavioral and Brain Sciences (2011)

Abstract Placeholders enable conceptual change only if presumed to be relevant (e.g., lead to the formation of true beliefs) even though their meaning is not yet fully understood and their cognitive function not yet specified. Humans are predisposed to make such presumptions in a communicative context. Specifying the role of the presumption of relevance in conceptual change would provide a more comprehensive account of Quinian bootstrapping.
Abstract 5408: Exploiting the defective p53/MDM2/p14<i>ARF</i> pathway in neuroblastoma by targeting checkpoint kinase Chk1 with AZD7762
Authors: Hong Xu, Xiao Wei, Irene Y. Cheung, Nai-Kong V. Cheung
Journal: Cancer Research (2010)

Abstract Introduction: A defective p53/MDM2/p14ARF pathway seems to be the principal mode of checkpoint dysfunction in metastatic neuroblastoma following DNA damage, which probably accounts for chemoresistance after initial treatment response. Checkpoint kinase inhibitor AZD7762 (AstraZeneca, currently in clinical trials) has the potential to enhance the action of DNA-damaging agents in some advanced solid malignancies. In this study, we assessed the potential synergy between AZD7762 and chemotherapeutic agents in the in vitro and in vivo treatment of neuroblastoma cells which harbor aberrations in the p53/MDM2/p14ARF pathway. Experimental Design: AZD7762 was tested in combination with chemotherapeutic agents both in vitro and in vivo against a representative panel of neuroblastoma cell lines. Ten were p53/MDM2/p14ARF pathway-defective (four with p53 mutations, three with MDM2 amplification, and three with p14ARF deletion) and three were wild type. Using these lines, p53/p21 functional assay, drug induced cytotoxicity, S/G2 checkpoint abrogation, and therapy of xenografts were examined. Synergism with chemotherapy was quantified using combination index (CI). CI&amp;lt;1 indicates synergism, CI=1 additive effects, and CI&amp;gt;1 antagonism. Results: Based on p53/p21 functional assays, all four p53 mutant lines failed to show endogenous p21 induction after DNA damage (defined as p53 pathway nonfunctional). Similarly, p53 was nonfunctional in two of the three MDM2 amplified and one of the three p14ARF deleted cell lines. In cytotoxicity assays, p53 nonfunctional lines were more resistant to DNA-damaging agents when compared to p53 functional lines. Synergy between AZD7762 and DNA-damaging agents (cisplatin, doxorubicin, etoposide, melphalan, SN38 and topotecan) was strong in all p53 nonfunctional lines (average CI values: 0.44 - 0.63), but not in p53 functional lines (average CI values greater than 1.0). In contrast, gemcitabine showed even stronger synergy with AZD7762 regardless of p53 functional status (CI values: 0.11 - 0.47). AZD7762 treatment resulted in the abrogation of DNA damage-induced S/G2 checkpoint arrest, and in the potentiation of antitumor activity of DNA-damaging agents in four mouse xenograft models. Conclusions: AZD7762 potentiated both in vitro and in vivo the antitumor effects of DNA-damaging agents against neuroblastoma. These results suggest that the addition of AZD7762 may reverse or prevent drug resistance, especially if a defective p53/MDM2/p14ARF pathway is the underlying mechanism. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5408.
P5-07-07: Follistatin Suppresses In Vitro Growth of Breast Cancer Cells and Its Reduced Expression in Breast Cancer Associated with Poor Differentiation and Prognosis.
Authors: L Ye, RE Mansel, WG Jiang
Journal: Cancer Research (2011)

Abstract Background: Bone morphogenetic protein (BMP) belongs to TGF-β superfamily, being widely involved in prenatal and postnatal development and homeostasis of various tissues and organs. BMP signaling has been implicated in tumorigenesis and disease progression of certain malignancies. Recent studies demonstrated a profound role played Noggin, a BMP antagonist in bone metastasis from breast cancer. Current study examined expression of Follistatin, another BMP antagonist in a breast cancer cohort, and its relevance to pathological and clinical parameters. Methods: Expression of Follistatin was examined in breast cancer tissues (n=93) and normal background tissues (n=30) using quantitative real time PCR and immunhistochemistry (IHC). The breast tissue samples were collected immediately after surgery. The clinical follow-up was routinely performed after surgery. The median follow-up period was 120 months (June 2004). Full-length human Follistatin coding sequence was cloned into a plasmid vector. Following transfection and verification, effect of Follistatin overexpression on cell growth was examined using an in vitro growth assay. Results: IHC revealed cytoplamic staining of Follistatin in mammary epithelial cells in breast tissues. The staining appeared to be weaker in breast cancer, but there was no significant difference in its transcripts levels compared with that of normal background tissues. Follistatin transcripts were decreased in both moderately differentiated and poorly differentiated tumors, p=0.0165 and p=0.0169 in comparison with well differentiated tumors respectively. Transcript levels of Follistatin in primary tumors tended to be lower in the patients with poor prognosis (33.8±14.7) including those patients had local recurrence, metastases and died of breast cancer, p=0.09 when compared with that of patients remained disease free (117.0±46.0). Its expression appeared particularly lower in the patients died of the disease (21.8±12.0), p=0.05 v.s. disease free. Over-expression of Follistatin exerted inhibitory effect on in vitro growth of MDA-MB-231 cells. Conclusions: Decreased expression of Follistatin in primary tumors of breast cancer correlates with poorer differentiation and mortality. Follistatin suppresses in vitro growth of breast cancer cells. It suggests that Follistatin is a negative regulator for tumor growth and disease progression of breast cancer. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P5-07-07.
Endothelial cell support of hematopoiesis is differentially altered by IL-1 and glucocorticoids
Authors: B Jazwiec, A Solanilla, C Grosset, F-X Mahon, M Dupouy, V Pigeonnier-Lagarde, F Belloc, K Schweitzer, J Reiffers, J Ripoche
Journal: Leukemia (1998)
Unusually high frequency of a 69-bp deletion within the carboxy terminus of the LMP-1 oncogene of Epstein–Barr virus detected in Burkitt’s lymphoma of Turkish children
Authors: N Tacyildiz, AO Cavdar, U Ertem, A Oksal, L Kutluay, O Uluoglu, J-C Lin
Journal: Leukemia (1998)
Pyogenic granuloma in the small intestine: a rare cause of obscure gastrointestinal bleeding
Authors: Masaki Katsurahara, Takashi Kitade, Shunsuke Tano, Yasuhiko Hamada, Hiroyuki Inoue, Kyosuke Tanaka, Noriyuki Horiki
Journal: Endoscopy (2015)

A 65-year-old man with a history of cerebral infarction was referred to our hospital for investigations to find the cause of recurring melena, which he had been experiencing for 2 months. At a previous hospital, he had had an upper gastrointestinal endoscopy and a colonoscopy that failed to show a cause for his bleeding, and an abdominal computed tomography (CT) scan, which detected a strongly enhancing mass in the upper abdomen ([Fig. 1]).
FRI0366 What is the Predictive Value of A Family History of Arthritis-Related Conditions on the Risk of Rheumatoid Arthritis, and Does IT Differ between Seropositive and Seronegative Disease?:
Authors: T. Frisell, K. Hellgren, J. Askling
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Although family history of arthritis-related diseases is routinely collected as part of the work-up for rheumatoid arthritis (RA) in clinical practice, the interpretation of such information is often difficult since the relative importance of a family history of different arthritic and inflammatory diseases - beyond the established familial association of RA itself - is little known. Further, recent studies suggest that seropositive and seronegative RA have unique as well as shared genetic risk factors. However, with the exception of the HLA region, little is known about which genes or pathways are different between the two disease subsets. <h3>Objectives</h3> To assess the difference in predictive value of a family history of arthritis-related conditions for seropositive and seronegative RA, incidentally exploring the possible genetic difference of these disease subsets. <h3>Methods</h3> Register-based nested case-control study in the Swedish total population. RA was ascertained through the nationwide Patient register and the Swedish Rheumatology Register. First degree relatives were ascertained through the Swedish Multi-Generation Register. Autoimmune and arthritis-related diseases in relatives were assessed through the Patient register. Familial risks where calculated using conditional logistic regression with robust standard errors. <h3>Results</h3> Family history of seropositive RA was the strongest predictor of RA in the proband, regardless of serostatus. Statistically significant familial co-aggregation with RA was found for every arthritis-related disease under study, but risk increases varied widely (Table). With the exception of family history of RA itself, the difference in familial co-aggregation was very small for seropositive and seronegative RA. When combinations of family histories were examined, no arthritis-related disease added information beyond that provided by a family history of RA. <h3>Conclusions</h3> Seropositive and seronegative RA does not appear to differ much in the genetic risk factors that are shared with other arthritis-related diseases. Although a family history of (either of) several non-RA arthritis-related diseases is predictive of RA, the impact of others (e.g., osteoarthritis, unspecified athralgia) is negligible. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.1720