tbuckley/cabot-search huggingface dataset:
ARE OUTCOMES FOLLOWING LAPAROSCOPIC RESECTION FOR INFLAMMATORY BOWEL DISEASE IN ADULTS AND CHILDREN COMPARABLE?
Authors: C McMullin, J Morton, S Vickramarajah, M Brennan, C Salvestrini, F Torrente, R Heuschkel, R J Davies
Journal: Gut (2013)

<h3>Introduction</h3> Inflammatory bowel disease (IBD) has prevalence in Europe of approximately 2.2 million, with evidence of increasing incidence in the paediatric population. Up to 40% of patients will require surgery for their disease, the majority within the first year of diagnosis. <h3>Aims/Background</h3> Since 2007, a single surgeon whose main practice is in adults has performed laparoscopic resectional surgery for IBD in adults and children within separate IBD multidisciplinary teams. Our aim was to assess short-term outcomes for adults and children following laparoscopic resectional surgery for IBD. <h3>Method</h3> Analysis of a prospectively collected database was carried out to include all patients who had undergone a laparoscopic resection for IBD (excluding stoma formation alone and ileoanal pouch surgery) under the care of one surgeon between December 2007 and July 2012. <h3>Results</h3> Fifty-nine patients underwent laparoscopic resections (28 children and 31 adults). Median age for children was 14 (range 8–16) years and adults 32 (range 21–63) years. The median BMI for adults was 23 (range 18–38) and 19.5 (range 13–29.5) for children (p= 0.0006). Operative times for adults and children were similar with a median of 210 and 165 minutes respectively (p=0.09). Postoperative complication rates were not significantly different: 6 (19%) in the adult population and 4 (14%) in children (p=0.73). Median length of stay was 5 days in adults vs 6 days in children (p=0.09). <h3>Conclusion</h3> Laparoscopic surgery in children is safe when performed by an experienced surgeon whose normal practice is in adults, with acceptable outcomes when compared to adults.
Distribution of C-Reactive Protein Values in the United States
Authors: Steven Woloshin, Lisa M. Schwartz
Journal: New England Journal of Medicine (2005)

In reply to the letter from Grass (Jan.13 issue), 1 we would like to clarify that www.clinicaltrials.govwas expanded in October 2004 to allow for the registration of any clinical trial that has been approved by a human subjects review board (or the equivalent) and that conforms to the regulations of the appropriate national or international health authority.We encourage investigators and sponsors of clinical trials that meet these criteria to register their trials at this Web site.In addition, current U.S. law mandates the registration of trials that are designed to evaluate the efficacy of drugs for the treatment of serious or lifethreatening diseases and that are intended to support a new drug application to the Food and Drug Administration. 2 For more information about registration of clinical trials, see http://prsinfo.clinicaltrials.gov.
S134 Kinase Selectivity Profiles Of Nintedanib And Imatinib
Authors: R. Rajagopalan, J. Nicholas, S. Misialek, S. Buckman, S. Seiwert
Journal: Thorax (2014)

<h3>Introduction</h3> Tyrosine kinase inhibition has shown inconsistent success in the treatment of idiopathic pulmonary fibrosis (IPF). While a study of imatinib showed no impact on survival or lung function in a placebo-controlled study, two recently announced placebo-controlled phase 3 trials of nintedanib demonstrated statistically significant impact on forced vital capacity. Comparing the kinase target profiles could inform future target selection for drugs in IPF. <h3>Methods</h3> <i>In vitro</i> kinase selectivity data of nintedanib and imatinib were collected using the kinomescan platform (DiscoveRx Inc). Binding data (% binding) for 451 human kinases (~80% of the human kinome) were initially collected at a single concentration (10 uM). For kinases that displayed significant binding, potencies (K<sub>D</sub>) were measured in dose-response format. <h3>Results</h3> At a common concentration of 100 nM, imatinib and nintedanib bound to 12 and 50 kinases, respectively. Maximal drug concentrations (C<sub>max</sub>) observed in patients were used to project therapeutically relevant kinase inhibition for both drugs. Using these criteria, nintedanib binds 44 kinases at drug levels seen in patients (K<sub>D</sub> &lt; C<sub>max </sub>of 64 nM). Imatinib binds 34 kinases at drug levels seen in patients (K<sub>D</sub> &lt; C<sub>max </sub>of 7500 nM). 14 kinases were bound by both compounds, including PDGFRA, PDGFRB and VEGFR2. <h3>Conclusions</h3> Our results suggest that nintedanib and imatinib have partially overlapping inhibition profiles; the kinases that are targeted by both agents are unlikely to be responsible for efficacy differences. Further work is required to identify which of the remaining kinase target (s) are responsible for efficacy in IPF and could therefore represent targets for follow-up compounds.
FRI0165 A prediction tool for drug monitoring of adalimumab in rheumatoid arthritis.
Authors: E. Ducourau, D. Ternant, P. Fuzibet, T. Lequerré, G. Paintaud, X. Le Loët, P. Goupille, O. Vittecoq, D. Mulleman
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Adalimumab, an anti-TNF-α monoclonal antibody, is effective in active rheumatoid arthritis (RA). There is a relationship between adalimumab concentration and clinical response but it has never been quantified individually. <h3>Objectives</h3> To describe the individual relationship between adalimumab concentration and disease activity in RA patients and to select an adalimumab target concentration necessary to reach either a low disease activity or clinical remission. <h3>Methods</h3> We measured adalimumab concentration in 127 samples from 30 RA patients who received 40 mg subcutaneously every other week. Disease activity score (DAS 28) were available at baseline, and at weeks 6, 12, 24 and 52. The relationship between adalimumab concentrations and DAS 28 was described by pharmacokinetic-pharmacodynamic (PK-PD) modelling using a direct inhibitory model. <h3>Results</h3> Median adalimumab concentrations increased over all the year whereas median DAS 28 decreased. At steady state, median adalimumab concentration [min-max] was 7.8 mg/L [1.8-15.0] and median DAS 28 was 2.9 [0.8-6.3]. The concentration-response relationship of adalimumab was well described by the direct inhibitory model. For a typical patient, adalimumab concentration required to decrease baseline DAS28 by 2 was 11.8 mg/L. The relationship between baseline DAS 28 and adalimumab concentration at steady state is displayed in figure 1. It shows that, if baseline DAS 28 is 6, the steady state adalimumab concentration necessary to achieve a low disease activity is 10 mg/L with 25%&gt;75% confidence interval of 5-20 mg/L. To achieve remission, the required adalimumab concentration is 15 mg/L [8-30 mg/L]. <h3>Image/graph</h3> <h3>Conclusions</h3> This is the first study describing the individual concentration-effect relationship of adalimumab in RA. This model can be used to select the target concentration of adalimumab when therapeutic drug monitoring is applied. <h3>Acknowledgements</h3> Pr. Christian Marcelli. CHU Caen, Pr. René-Marc Flipo. CHU Lille, Pr. Patrice Fardellone. CHU Amiens <h3>Disclosure of Interest</h3> None Declared
P5-23-01: The Impact of Primary Tumor Resection on the Survival of Patients with Stage IV Breast Cancer According to Molecular Subtype.
Authors: SK Ahn, H-G Moon, JS Kim, JM You, HC Shin, W Han, D-Y Noh
Journal: Cancer Research (2011)

Abstract Purpose: The main treatment for stage IV breast cancer is currently systemic therapy. Surgical resection of the primary tumor is usually done for treating the tumor-related complications. Recent studies have suggested that surgery may improve the long-term survival of stage IV breast cancer patients. We evaluated the impact of the primary surgical resection site on the survival of stage IV breast cancer patients according to molecular subtype using nationwide Korean breast cancer registry data. Methods: We analyzed the records of the stage IV breast cancer patients from Korean Central Cancer Registry (KCCR) between 1999 and 2008. We used clinical assays to distinguish luminal A (HR+/HER2−, n=290), luminal B (HR+/HER2+, n=154), Basal-like (HR-/HER2−, n=107) and HER2 (HR-/HER2+, n=145). The clinical and tumor characteristics, the type of treatments and the overall survival were compared between the surgically versus nonsurgically treated patients according to molecular subtype. Results: Of the 1091 identified patients, 719 (65.9%) received surgical excision of their primary tumor and 372 (34.1%) did not. The mean survival was 86 months versus 43 months for the surgically treated patients vs. the patients without surgery, respectively (p&amp;lt;0.001). On a multivariate analysis with using the Cox model and after adjusting for tumor size, visceral metastases, the number of metastatic sites and bone only metastases, surgery was an independent factor for improved survival in patients with luminal A type (Hazard Ratio, 0.505; 95% Confidence Interval, 0.265−0.962, p=0.038) but not in those with luminal B (p=0.192), basal-like (p=0.128) and HER2 subtype (p=0.114). Conclusion: Surgical resection of the primary tumor in stage IV breast cancer patients was independently associated with improved survival only in luminal A subtype. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P5-23-01.
Special Commission on Breast Cancer To Issue Final Report
Authors: T. Parkins
Journal: JNCI Journal of the National Cancer Institute (1993)

Journal Article Special Commission on Breast Cancer To Issue Final Report Get access Troy Parkins Troy Parkins Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 85, Issue 17, 1 September 1993, Page 1374, https://doi.org/10.1093/jnci/85.17.1374 Published: 01 September 1993
Floating Stools — Flatus versus Fat
Authors: Michael D. Levitt, William C. Duane
Journal: New England Journal of Medicine (1972)

Factors influencing the density of stools from 33 healthy subjects (nine had floating and 24 sinking stools) and six patients with steatorrhea were investigated. All floating stools sank when their gas volume was compressed by positive pressure. Thus, to float, stools must contain gas. After degassing, previously floating and sinking stools had similar specific gravities, indicating that the floating or sinking propensity of such stools depends upon differences in gas rather than fat content. A high stool gas content (and hence a floating stool) in healthy subjects appeared related to colonic methane production. Steatorrheic stools had a relatively normal gas content. The density of their nongaseous fraction was less than normal, but resulted primarily from increased water rather than fat content. Thus, stools float because of an increased content of gas or water (or both); the floating stool should not be considered a sign of steatorrhea.
Abstract 5046: miR-199a/125b inhibits tumor growth
Authors: Bing-Hua Jiang, Jun He, Qing Xu, Stephen Peiper, Ling-Zhi Liu
Journal: Cancer Research (2012)

Abstract Many human cancers of epithelial origin are associated with overexpression of epidermal growth factor receptor (EGFR) family. In particular, ERBB2 and ERBB3 overexpression are linked with cancer development and poor prognosis. Except ERBB2/ERBB3 gene amplification, other mechanism(s) of ERBB2 and ERBB3 overexpression remains elusive. Recent studies show that aberrant expressions of miRNAs are associated with cancer development. To identify specific miRNAs for regulating ERBB2 and ERBB3 expression, we find that miR-199a and miR-125b directly target ERBB2 and ERBB3, and are downregulated in ovarian tissues and cancer cells. Elevated reactive oxygen species (ROS) have been observed in tumor growth and drug resistance. Interestingly we show that increased ROS downregulate miR-199a and miR-125b for inducing ERBB2 and ERBB3 expression. ERBB2 and ERBB3 in turn activate AKT/P70S6K1/HIF signaling leading to tumor growth and angiogenesis. This study provides a novel mechanism of ERBB2 and ERBB3 regulation by miR-199a and miR-125b and new concept of ROS for inducing ERBB2 and ERBB3 in tumor growth and angiogenesis; and establishes a rationale for using miR-199a and miR-125b mimics and ROS scavengers as new therapeutic agents in the future. 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 5046. doi:1538-7445.AM2012-5046
INVOLUTIONAL MELANCHOLIA
Authors: C. C AULT, EMMETT F. HOCTOR, AUGUST A. WERNER
Journal: American Journal of Psychiatry (1940)

1. The recovery rate of patients having uncomplicated involutional melancholia treated with theelin in our hospital is above 90 per cent. 2. Larger dosages than were originally used by us, are more efficacious and are recommended. 3. In view of these results, other severe forms of treatment, such as metrazol shock, do not seem justified in uncomplicated involutional melancholia, unless adequate estrogenic treatment fails to give relief.
New Technologies Profoundly Change Cancer Research In 20 Years
Authors: J. Waalen
Journal: JNCI Journal of the National Cancer Institute (1991)

Journal Article New Technologies Profoundly Change Cancer Research In 20 Years Get access Jill Waalen Jill Waalen Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 83, Issue 1, 2 January 1991, Pages 6–8, https://doi.org/10.1093/jnci/83.1.6 Published: 02 January 1991
Legislative Update: NIH Reauthorization Bill Signed
Authors: D. A. Tisevich
Journal: JNCI Journal of the National Cancer Institute (1993)

Journal Article Legislative Update: NIH Reauthorization Bill Signed Get access Dorothy A. Tisevich Dorothy A. Tisevich Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 85, Issue 15, 4 August 1993, Pages 1194–1195, https://doi.org/10.1093/jnci/85.15.1194 Published: 04 August 1993
AB0538 Rate, Risk Factors and Causes of Mortality in Patients with SjÖGren's Syndrome: A Systematic Review and Meta-Analysis of Cohort Studies
Authors: A. Singh, S. Singh, E. Matteson
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> There is conflicting evidence regarding prognosis in patients with primary Sjögren9s syndrome (pSS). <h3>Objectives</h3> We estimated rate, risk factors and causes of mortality in patients with pSS through a systematic review and meta-analysis. <h3>Methods</h3> Through a systematic review of multiple databases through October 2014, we identified cohort studies reporting relative risk (compared to standardized population), risk factors and causes of mortality in patients with pSS. We estimated summary risk ratios (RR) with 95% confidence intervals (CI), using random effects model. <h3>Results</h3> We identified 10 studies with 7,888 patients (91% females) with pSS, of whom 682 patients died over a median average follow-up of 9 years. Pooled standardized mortality ratio in patients with pSS was 1.38 (95% CI, 0.94-2.01). Leading causes of mortality were cardiovascular diseases, solid-organ and lymphoid malignancies and infections. Risk factors associated with mortality were: advanced age at diagnosis (RR, 1.09; 95% CI, 1.07-1.12), males (RR, 2.18; 95% CI, 1.45-3.27), parotid enlargement (RR, 1.81; 95% CI, 1.02-3.21), abnormal parotid scintigraphy (RR, 2.96; 95% CI, 1.36-6.45), extraglandular involvement (RR, 1.77; 95% CI, 1.06-2.95), vasculitis (RR, 7.27; 95% CI, 2.70-19.57), anti-SSB positivity (RR, 1.45; 95% CI, 1.03-2.04), low C3 (RR, 2.14; 95% CI, 1.38-3.32) and C4 (RR, 3.08; 95% CI, 2.14-4.42) and cryoglobulinemia (RR, 2.62; 95% CI, 1.77-3.90). <h3>Conclusions</h3> pSS is not associated with an increase in all-cause mortality, as compared to the general population. However, a subset of patients with extraglandular involvement, vasculitis, hypocomplementemia and cryoglobulinemia may be at increased risk of mortality, and require close follow-up. <h3>Disclosure of Interest</h3> None declared
Abstract LB-172: MicroRNAs mediate the inhibition of tumor cell invasion by sulindac
Authors: Xiaobo Li, Lin Gao, William Taylor, Lalita Shevde, Rajeev Samant, Windy Dean-Colomb, Gary A. Piazza, Yaguang Xi
Journal: Cancer Research (2012)

Abstract A large body of evidence indicates that nonsteroidal anti-inflammatory drugs (NSAIDs) have strong antineoplastic properties against a broad range of cancer types in early or late stage animal models of tumorigenesis. However, their use in humans for chemoprevention is limited by toxicities resulting from cyclooxygenase (COX) inhibition and the suppression of physiologically important prostaglandins. The anticancer properties of NSAIDs are generally attributed to the suppression of tumor cell proliferation and induction of apoptosis by inhibiting cyclooxygenase (COX), although numerous studies suggest that a COX-independent mechanism may either contribute to or be fully responsible for their activity. The effect of NSAIDs on tumor cell motility and invasion has not been well studied, despite clinical studies showing that certain NSAIDs can significantly increase the survival of patients with metastatic disease. Our results show that the NSAID, sulindac sulfide (SS) can potently inhibit the motility of human breast (MDA-MB-231 and SUM1315) and colorectal (HCT116 and HT29) tumor cells by a mechanism that is distinct from its tumor cell growth and COX inhibitory activity. To study the molecular basis for this activity, we investigated the involvement of microRNA (miRNA). A total of 132 miRNAs were found to be altered in response to SS treatment including miR-10b, miR-17, miR-21, and miR-9, which have been previously implicated in tumor invasion and metastasis. We confirmed that these miRNAs can stimulate tumor cell invasion and show that SS can attenuate their invasive effects (individual and cooperative) by down-regulating their expression. Employing luciferase and chromatin immunoprecipitation (ChIP) assays, NF-κB was found to bind the promoters of all four miRNAs to regulate their expression at the transcriptional level. Results from the immunofluorescence and Western Blotting assays show that SS can inhibit the translocation of NF-κB to the nucleus by decreasing the phosphorylation of IKKβ and IκB, which leads to down-regulation of these miRNAs. Analysis of the promoter sequences of the miRNAs suppressed by SS revealed that 81 of 115 sequences contained NF-κB binding sites. Our results demonstrate that SS can inhibit tumor cell invasion by suppressing NF-κB mediated transcription of miRNAs, which illustrate the mechanistic basis of this novel anticancer property of sulindac on tumor progression and metastasis. We expect these results are capable of supporting future clinical trials of sulindac in patients with metastatic disease. 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 LB-172. doi:1538-7445.AM2012-LB-172
SAT0182 Urinary T cells identify SLE patients with proliferative lupus nephritis and may be used to monitor treatment response
Authors: P. Enghard, C. Rieder, K. Kopetschke, J. Klocke, J. Humrich, R. Undeutsch, R. Biesen, G.-R. Burmester, G. Riemekasten
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Lupus nephritis (LN) is one of the main concerns in the treatment of patients with SLE. However there are no good laboratory markers to non-invasively detect and monitor kidney inflammation in patients with LN. We and others have previously reported that urinary CD4 T cells may serve as a biomarker for acute LN, however these existing studies are limited by their relatively small sample size. <h3>Objectives</h3> To confirm that urinary CD4 T cells reflect lupus nephritis activity and may serve as a marker to monitor the local inflammation in the kidneys. <h3>Methods</h3> Urine samples from 118 patients with SLE and 10 healthy controls were analyzed using flowcytometry and correlated with the disease activity (SLEDAI). 24 SLE patients were analyzed at the same time point of receiving a kidney biopsy. <h3>Results</h3> In patients with renal involvement the amount of urinary CD4 T cells correlated closely with the disease activity (SLEDAI), while patients without renal involvement showed only marginal amounts of urinary T cells even during lupus flares. Healthy controls showed no urinary T cells. All patients with biopsy demonstrated proliferative LN showed highly elevated amounts of urinary CD4 T cells, while some patients with class V nephritis presented normal amounts of urinary T cells. Under treatment for acute LN one patient group quickly normalized the amount of urinary CD4 T cells while others showed a persistence of elevated urinary CD4 T cells counts. The latter patient group had a significantly higher disease activity 6 month after induction of treatment compared to the patients with normalized urinary CD4 T cells, indicating that urinary T cell count reflect treatment response. <h3>Conclusions</h3> Elevated numbers of urinary CD4 T cells reliably identify SLE patients with proliferative LN. Furthermore the amount of urinary CD4 T cells under treatment seems to reflect treatment response. We consequently propose that urinary CD4 T cells can be used to screen for proliferative LN and to monitor the LN activity under treatment. <h3>Disclosure of Interest</h3> None Declared
Enhanced ability of daniplestim and myelopoietin-1 to suppress apoptosis in human hematopoietic cells
Authors: JA McCubrey, WL Blalock, O Saleh, M Pearce, C Burrows, LS Steelman, JT Lee, RA Franklin, SM Oberhaus, PW Moye, PD Doshi, JP McKearn
Journal: Leukemia (2001)