tbuckley/cabot-search huggingface dataset:
AB1280 Diurnal variation of power doppler signal in metacarpophalangeal joints of patients with rheumatoid arthritis
Authors: L. Semerano, M. Gutierrez, A. Ariani, G. Falgarone, E. Filippucci, N. Saidenberg-Kermanac’h, M.-C. Boissier, W. Grassi
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> In a preliminary study on 10 patients with active rheumatoid arthritis (RA) we could show for the first time that Power Doppler ultrasonography (PDUS) signal of metacarpophalangeal (MCP) joints has a clear diurnal variation, being higher in the morning vs. early afternoon and evening. We extended our study and involved a total of 36 patients with active RA in order to confirm our preliminary results <h3>Objectives</h3> To test, in a larger series, whether PDUS signal of MCP joints in RA patients varies according to the time of day <h3>Methods</h3> A total of 360 MCP joints from 36 patients with active RA (DAS28&gt;3,2) were evaluated for both presence-absence of PDUS signal and according to a semiquantitative score at three different times of day T0: between 7 and 10 a.m.; T1: 4-6 hours after T0; T2: 4-6 hours after T1. The scores at T0, T1 and T2 were compared for each joint. Before each PDUS examination the patient filled out a 100 mm visual scale of pain (VAS). The day of PDUS assessment, factors that could potentially influence PDUS signal or VAS results were minimized. All patients seated in a temperature-controlled room for at least 30 minutes before PDUS examination to stabilize the blood flow. They avoided smoke, alcohol, corticosteroids, NSAIDs, analgesics and vasoactive drugs intake. Room temperature was kept stable. For PDUS examination patients put their hands inside a silhouette drawn on the paper sheet lying on the bench to avoid any change in hands' position across the three examinations. <h3>Results</h3> PDUS presence/absence: there was a significant variation in the number of positive MCP joints during the day (p=0.01). There were more PDUS positive MCP joints at T0 (109) vs. T1 (97) (p&lt;0.05) and vs.T2 (93) (p&lt;0.05). Semiquantitative PDUS scores were significantly higher at T1 (mean rank 2.19) with a subsequent reduction at T2 (mean rank 1.93) (p&lt;0,05) and at T3 (mean rank 1.88) (p&lt;0,05). PDUS scores correlated with pain visual scale values at T0, T1 and T2 (rho 0,54; p&lt;0,001). All patients displayed some sort of circadian variation, and the vast majority had higher scores at T1, nevertheless some patients (3) had higher scores at T2 or T3. <h3>Conclusions</h3> Diurnal variation of PDUS signal of MCP joints is a feature of patients with active RA and correlates with joint pain. The vast majority of patients displays higher PDUS signal in the morning compared to afternoon and evening, but some selected patients may have a different circadian variation, with higher signal later during the day. <h3>Disclosure of Interest</h3> None Declared
S131 Peripheral Blood Mononuclear Cells From Children With Severe Asthma Exhibit An Impaired Corticosteroid Sensitivity, Which Also Correlates With Increasing Body Mass Index
Authors: N. Yemula, E. Gaillard, Y. Amrani
Journal: Thorax (2014)

<h3>Introduction</h3> Corticosteroid (CS) insensitivity contributes to the difficulty in managing children with severe asthma.<sup>1</sup> A better understanding of the molecular mechanisms driving this defective response could provide novel therapeutic options for these patients. Peripheral blood mononuclear cells (PBMCs) from adults with severe asthma have been used to demonstrate an impaired sensitivity to CS, enabling the delineation of potential underlying mechanisms. Whether CS insensitivity exists in PBMCs from severely asthmatic children, however, requires further validation. <h3>Objective</h3> To determine whether PBMCs from children with severe asthma have an impaired <i>in vitro</i> responsiveness to corticosteroids. <h3>Methods</h3> We conducted an observational feasibility study comparing the corticosteroid sensitivity of PBMCs from asthmatic children on British Thoracic Society treatment step 4–5 (n = 7) with healthy controls (n = 5). PBMCs from 5 ml of venous blood were plated in the presence of 100 ng/ml of lipopolysaccharide (LPS), and in the absence or presence of either 10<sup>–8 </sup>M or 10<sup>–6 </sup>M of dexamethasone (DEX). ELISA assays were used to determine the levels of TNF-α and IL-8, and the% suppression of these by DEX. Pearson product-moment correlation tests were conducted to determine the correlation between <i>in vitro</i> CS sensitivity and different clinical parameters. <h3>Results</h3> There was no difference in baseline or LPS-induced cytokine release from PBMCs between the two groups. The inhibition of TNF-α release by DEX was significantly diminished in children with asthma compared to healthy controls at 10<sup>–8 </sup>M concentration (<i>p = 0</i>.018) but no differences were noticed at 10<sup>–6 </sup>M concentration, or on LPS-induced IL-8 production. A significant inverse correlation between% inhibition of TNF-α and body mass index (BMI) at 10<sup>–8 </sup>M (r=-0.84, <i>p = 0</i>.02) and 10<sup>–6 </sup>M DEX (r=-0.82, <i>p = 0</i>.02) was found. <h3>Conclusions</h3> Our results show the existence of an impaired CS sensitivity in PBMCs from children with severe asthma, suggesting that these cells can be used for mechanistic investigations. Interestingly, we observed a negative correlation between CS sensitivity and BMI, a novel <i>in vitro</i> finding which supports the association between overweight/obese asthmatic children and a decreased clinical response to CS therapy. Together, these results merit further studies with a larger sample size. <h3>References</h3> Chung KF <i>et al</i>.<i> ERJ</i> 2014;43:343–373
Hypertension (HTN) in National Cancer Institute of Canada Clinical Trials Group study BR.24: A randomized, double-blind phase II trial of carboplatin (C) and paclitaxel (P) with either daily oral cediranib (CED), an inhibitor of vascular endothelial growth factor receptors, or placebo, in patients with advanced non-small cell lung cancer
Authors: R. A. Goodwin, L. Seymour, K. Ding, I. Gauthier, A. Le Maitre, E. Frymire, A. Arnold, F. A. Shepherd, G. D. Goss, S. A. Laurie
Journal: Journal of Clinical Oncology (2009)

3527 Background: CED 30 mg/d with C+P increased response rate (RR: 38 vs 16% p &lt; 0.0001) and median progression free survival (PFS: 5.6 vs 5 m, hazard ratio [HR] 0.77) over C+P alone. HTN is a known effect of angiogenesis inhibitors (AI). For BR.24, we describe the incidence of HTN, effects on drug delivery, predictors of its development/worsening, and assess the predictive effect of HTN on efficacy. Methods: Pts received C+P plus either placebo (n =146) or CED (n = 148). HTN as an adverse event (HTN AE: defined as either new onset HTN, or worsening grade HTN in a previously hypertensive pt), was managed with a protocol-defined algorithm. Exploratory analyses characterized the relationship between HTN AE and baseline characteristics and treatment arm. Kaplan Meier curves summarized time to event outcomes and Cox regression models with time dependent covariates correlated HTN AE to outcomes. Results: Rate of pts with a history of HTN were similar: CED 26 %, placebo 33 %. CED pts had significantly higher HTN AE (any: 38 vs 12%, p &lt; 0.0001; grade 3 or 4: 19 vs 2 %). With the treatment algorithm, HTN AE had minimal impact on drug delivery (1 pt interrupted C+P, 11 pts [3.7%] reduced /discontinued CED / placebo). Headache was the only other AE that correlated with HTN AE. Predictors of HTN AE included: CED arm (p &lt; 0.0001), good ECOG (p = 0.02), female (p = 0.006), history of HTN (p = 0.06). CED pts with HTN AE had significantly higher RR (51.8 vs 32.6%, p = 0.025) and PFS (8.5 vs 5.1 m; HR 0.45, 95% CI 0.29 to 0.72, p = 0.0007); similar but not significant findings were observed with placebo (RR 35.3 vs 17.2%, p= 0.098; PFS 5.6 vs 4.9 m; HR 0.84, 95 % CI 0.45–1.54); the interaction term by treatment arm was not significant. Conclusions: CED pts had greater HTN AE, but this did not impact drug delivery. Certain baseline characteristics predicted HTN AE in all pts. Unexpectedly, development of on-study HTN predicted improved outcome in all pts, although to a greater extent for those on CED. Additional evaluation of the role of HTN AE as a predictor of efficacy of both AI and cytotoxics is warranted. [Table: see text]
Patenting Bio-Property
Authors: Guy McCLUNG
Journal: JNCI Journal of the National Cancer Institute (1989)

Journal Article Patenting Bio-Property Get access GUY McCLUNG GUY McCLUNG Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 81, Issue 13, 5 July 1989, Page 1042, https://doi.org/10.1093/jnci/81.13.1042-a Published: 05 July 1989
Abstract LB-357: Efficient identification of tumor of unknown primary origin by its microRNA profile
Authors: Rolf Søkilde, Anne K. Møller, Martin Vincent, Boye S. Nielsen, Alastair Hansen, Gedske Daugaard, Søren Møller, Thomas Litman
Journal: Cancer Research (2010)

Abstract Background: Carcinomas of unknown primary origin (CUP) constitute 3-5% of all newly diagnosed metastatic cancers, the primary source of which is hard to classify with current histological methods, often because CUPs are poorly differentiated. Since effective cancer treatment depends on early and proper identification of the tumor, CUP patients have poor prognosis and short survival rates. Increasing evidence suggests that microRNAs play an important role in the initiation and progression of cancer, and because the expression of microRNAs is highly tissue specific, the microRNA profile of an unknown tumor can be used to identify its tissue of origin. Here, we present a microRNA based classifier, which based on a sample's microRNA profile, can predict its tissue origin with high accuracy. Methods: Total RNA was extracted from 1115 formalin fixed paraffin embedded (FFPE) samples, and subjected to expression analysis on an LNA (Locked Nucleic Acid) enhanced microarray platform, which allows for very sensitive and specific detection of 2090 microRNAs. Based on the microRNA expression profiles, we tested and cross-validated several classification algorithms, including KNN (K nearest neighbors), LDA (linear discriminant analysis), SVM (support vector machines) and LASSO (least absolute shrinkage and selection operator) to assess, which method is best suited for the current multiclass classification task. Results: The currently best classifier for tumors of unknown primary origin is based on the LASSO algorithm, which consistently is able to identify 15 different tumor histologies with 90% or higher accuracy based on a small set of microRNAs. We are currently assessing the classifier's performance on true unknown primary tumors, where the correct diagnosis has been obtained at autopsy. 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 LB-357.
P66 Is Earlier CT Scanning For Lung Cancer Exposing Patients to an Increased Risk of Harm from Contrast Nephropathy?
Authors: B O’Leary, E Ghorani, AK Reinhardt
Journal: Thorax (2012)

<h3>Introduction</h3> Contrast induced nephropathy (CIN) is the third most common cause of hospital-acquired acute kidney injury <sup>1</sup> and is associated with increased incidence of requiring dialysis, and with increased mortality. This is particularly the case in those with pre-existing renal impairment or other co-morbidities, such as diabetes or heart failure. Computed tomography of the chest with IV contrast is now an integral part in the diagnosis and staging of patients with lung cancer. In an effort to reduce time to diagnosis, contrast studies are routinely performed early, often prior to first review in secondary care. As a result, this population may have inadequate assessment of CIN risk. To investigate this further we carried out a retrospective analysis of the monitoring of the renal function of patients with lung cancer who underwent a CT chest with contrast at a London teaching hospital. <h3>Methods</h3> A consecutive series of 100 patients diagnosed between November 2011 and January 2012 was identified using the local lung cancer registry. We examined how frequently renal function was monitored in relation to the patients’ CT chest scans. Whether this was clinically adequate was decided with reference to recommendations from the Royal College of Radiologists. <h3>Results</h3> Of 30 CKD patients, 14 (47%) had appropriate pre-contrast bloods. Of patients identified as having diabetes (n=10), 50% had appropriate pre-contrast bloods. Of 29 patients admitted acutely, 28 (97%) had appropriate pre-contrast bloods. Of the 37 remaining patients, outpatients with normal renal function, 26 (70%) had appropriate pre-contrast bloods. <h3>Conclusions</h3> This study demonstrated that almost all inpatients undergoing CT chest with IV contrast had appropriate monitoring of their renal function. However, this was true of a significantly lower proportion of outpatients. Perhaps of most concern was that approximately half of those patients at the highest risk of developing contrast-induced nephropathy were monitored appropriately. We suggest that earlier CT scanning, in the interests of expediting diagnosis and treatment, could be exposing more patients to increased risk of harm associated with administration of IV contrast. <h3>References</h3> Hou SH et al. Hospital-acquired renal insufficiency: a prospective study. Am J Med. 1983; 74243–8.
Abstract C36: Dc917 inhibits the growth of mouse lung carcinoma both in vitro and in vivo through cell cycle arrest and ERK signaling pathway
Authors: Hang Dong, Zhihong Jiang, Vincent Kam Wai Wong, Hua Zhou, Liang Liu
Journal: Cancer Research (2011)

Abstract Background: Chemotherapeutic agents often exhibit adverse effects to patients because of their nonspecific cytotoxic effect, and therefore we have screened anticancer compounds from a natural source. Dc917, a novel derivative from a Chinese medicinal plant, exhibited specific cytotoxic effect to a panel of cancer cells but no marked impairment to human normal lung fibroblasts, and it significantly suppressed tumor growth in xenograft-bearing mice. We thus aimed to further investigate molecular mechanisms of Dc917. Methods: Cell viability and cell cycle distribution were determined by MTT assay and flow cytometry, respectively. Immunoblotting was performed to determine changes in protein levels. Knockdown of desired protein was achieved by transfection with siRNA. Meanwhile, C57BL/6 mice bearing lung carcinoma cells were used to estimate the antitumor activity in vivo. Results: Dc917-induced significant cell cycle arrest in S phase was concomitant with downregulations of cdks and cyclins, as well as upregulations of p21 and p27 expression. The complex formation between cdk2/cyclin E and cdk4/cyclin D1 was reduced; however, the recruitment of p21 or p27 to cyclin E/Cdk2 complex was increased by Dc917 incubation. In addition, Dc917-induced cell death and S phase arrest were significantly attenuated by knockdown of p21 or p27 protein. Dc917 also induced MAPK and p53 pathway, which activated p27/p21 and subsequently suppressed cyclin/cdk complexes activity, and the inhibitor of ERK (U0126) could suppress Dc917-induced cytotoxicity and upregulation of p53/p27 or p21 and egr-1/p27 or/p21 expression. Conclusions: Our preclinical data indicated that Dc917 is a potential therapeutic agent in vitro and in vivo, and further development of this agent for cancer therapy is processing. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the Second AACR International Conference on Frontiers in Basic Cancer Research; 2011 Sep 14-18; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2011;71(18 Suppl):Abstract nr C36.
AB0990 Automated Ultrasound for the Detection of Synovitis in the Feet of Patients with Rheumatoid Arthritis (RA)
Authors: M. Witt, J. Frielinghausen, D.A. Clevert, J. Leipe, H. Schulze-koops, R.B. Mueller, M. Grünke
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> The automated breast volume scanner (ABVS), which was developed to acquire series of consecutive B-mode pictures of the female breast, has been used successfully for the detection of synovitis in finger joints of RA patients. <h3>Objectives</h3> To evaluate whether ABVS can be used for the detection of synovitis in foot joints of RA patients. <h3>Methods</h3> 30 patients with RA were examined clinically and by manual high resolution ultrasound. ABVS was conducted using the ACUSON S2000™. The ABVS transducer was equipped with a linear array (5 – 14 MHz band width); the frequency was set at 11 MHz. Each automatic sweep of the scanner generated 15.4 x 16.8 cm x maximum 3 cm volume data sets. The system was set to perform an automatic scanning time of 65 s per scan with a slice thickness of 0.5 mm. <h3>Results</h3> 30 patients with RA were examined. 23 of them were female, the mean age was 63 years, the mean DAS28 was 4.55 with mean 8.7 tender and 7.3 swollen joints. The feet were not evaluable due to metatarsophalangeal (MTP) joint resection or gross deformity in 10 patients, resulting in 200 evaluable MTP joints. Swelling was detected by clinical examination in 13% of all MTPs. Manual ultrasound revealed swelling in 25%, the ABVS in 27% of the MTP joints. <h3>Conclusions</h3> ABVS is a simple and time sparing option for effective detection of small joint synovitis not only in the hands but also the feet of patients with RA. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.3742
Confocal laser endomicroscopy for functional barrier imaging in Crohn’s disease
Authors: Markus Neurath
Journal: Endoscopy (2016)

Confocal laser endomicroscopy (CLE) is an endoscopic technique for microscopic assessment of the gastrointestinal mucosa, and was introduced into clinical practice in 2004 [1]. Initial studies used the technique to predict the presence of colonic neoplasias, but subsequent studies aimed to assess mucosal inflammation in the gastrointestinal tract. Specifically, CLE has been used for assessment of the intestinal mucosa in patients with inflammatory bowel diseases (IBD), such as Crohn's disease and ulcerative colitis. These studies revealed that CLE with fluorescein can be used to detect crypt alteration, hypervascularization, and infiltrating mononuclear cells in patients with IBD [2] [3]. Moreover, CLE with acriflavine was able to detect translocation of commensal bacteria into the inflamed mucosa [3], suggesting that this CLE approach may be suitable for the analysis of altered barrier function in IBD. Finally, in a pilot study of 47 patients with ulcerative colitis and 11 patients with Crohn's disease, Kiesslich et al. [4] demonstrated that detection of shedding epithelial cells and local barrier defects in the gut epithelium predict clinical relapse of quiescent IBD and can be quantitatively assessed by a new scoring system (Watson score).
Abstract P2-02-04: MRI Findings and Outcomes in an Underserved Breast Cancer Population Screened with <i>BRCA</i> Testing
Authors: S Tang, E Fahed, A Azadi, C Ricker, L Larsen, S Lee, P Jain, D Spicer, D. Tripathy
Journal: Cancer Research (2010)

Abstract Background: Patients with breast cancer and a familial risk and/or BRCA 1 or 2 mutations are at high risk of contralateral breast cancer and ipsilateral recurrence. While MRI screening is recommended for patients with BRCA mutations, and MRI staging for breast cancer is being increasingly used, the outcomes of such testing are not well described, especially in underserved populations. At Los Angeles County Hospital (LAC) for the last 3 years, we have enacted a program of genetic counseling and testing based standard guidelines as well as MRI evaluation of all patients newly diagnosed with breast cancer. LAC serves a population that includes a high number of indigent patients, primarily Hispanic (60%) and Asian (15%). Methods: We undertook a retrospective evaluation of all patients seen at LAC from March 2008 to March 2010 who underwent genetic counseling/testing and MRI as preoperative assessment for histologically documented breast cancer or followup after cancer treatment. IRB approval was obtained to extract data for this analysis. Demographic information along with clinical presentation, MRI and mammography results, additional imaging results, biopsy and surgical procedure and corresponding pathology data were obtained through the review of electronic medical records and clinic charts. Results: A total of 90 patients had both genetic testing and MRI reports available. The median age of all tested patients was 41 years. Ethnicity was 78% Hispanic, 9% Asian, 7% African American, 2% Caucasian and 4% other. BRCA mutation was seen in 20 cases (22%), 12 BRCA-1, 8 BRCA-2, 4 variants of unknown significance, and 66 had no mutation. Breast mass or other symptoms were the mode of detection in 89% of the overall cohort, and 81% in mutation carriers. The index lesion was visible on MRI in 78% and by mammogram in 82% of all patients. Ipsilateral MRI showed 7 abnormal non-index findings in 6 patients (7%); 6 of 7 lesions biopsied showed cancer. In the contralateral breast, 7 abnormalities were noted on MRI, but only 5 were amenable to biopsy as 2 could not be visualized by any means on follow up, and 1 showed cancer. Interestingly, only one of the 13 patients with abnormal findings carried a mutation (BRCA-1) and this patient did not have cancer on contralateral lesion biopsy. Mastectomy was performed in 91% and 78% of patients with and without mutation. Conclusions: Screening, counseling and testing for BRCA mutations is feasible in an underserved population, with a 22% mutation identification rate. MRI detected 5 non-index ipsilateral cancers and one contralateral cancer among 90 patients, with none of the detected cancers among the 20 mutation carriers. While MRI staging may be effective at detecting additional cancers in this underserved and high familial risk population, this appears to be independent of BRCA status. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P2-02-04.