tbuckley/cabot-search huggingface dataset:
Asymptomatic Mediastinal Lipomatosis
Authors: Prasanta Raghab Mohapatra, Ashok Kumar Janmeja
Journal: New England Journal of Medicine (2010)

A 58-year-old asymptomatic man with a history of gout presented for a routine physical examination. He was obese (weight, 91 kg; body-mass index [the weight in kilograms divided by the square of the height in meters], 31.1) and had decreased breath sounds at the right lung base. A chest radiograph revealed mediastinal widening with increased lucency (Panel A, arrows). Computed tomography (CT) of the thorax performed after the intravenous administration of contrast material revealed posterior collections of fat on both sides of the mediastinum, extending from the superior mediastinum to the diaphragm. The fat surrounded the heart and mediastinal structures . . .
SAT0030 Quality Indicators (QIS) in Rheumatoid Arthritis (RA) in Clinical Practice: Results from Measurement of Efficacy of Treatment in The ERA of Outcome in Rheumatology (Meteor) Database
Authors: V. Navarro-Compán, J. Smolen, T. Huizinga, R. Landewé, D. van der Heijde
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Quality indicators (QIs) are specific and measurable elements of practice that can be used to assess the quality of care by clinicians, managers and public. A set of recommendations is in development by an international task force in order to provide the achievable outcome of "best practice" in patients with rheumatoid arthritis (RA). <h3>Objectives</h3> To tested the feasibility to quantify the proposed QIs in patients with RA in clinical practice. <h3>Methods</h3> Data from all patients and visits included in METEOR database from Jan 2008 until Jan 2012 were analyzed to describe the assessment of QIs. The QIs we were able to collect were as follows: time to diagnosis since first symptoms onset, number of visits per year, frequency of disease activity assessment measured by any of the accepted scores, frequency of assessment of function (HAQ), proportion of patients in remission (DAS28 &lt;2.6, CDAI ≤2.8 or SDAI ≤3.3), proportion of patients with low disease activity (DAS28 &lt;3.2), and proportion of patients with low HAQ (≤ 0.25 in early RA patients and ≤ 0.5 in established RA patients). <h3>Results</h3> Data from 12,487 patients and 46,005 visits were included. Patients' characteristics are shown in table 1A. Median (IQR) values for time to diagnosis (months) and number of visits per year were 6.0 (2-18) and 2.9 (2.0-4.3), respectively. The assessment of HAQ and at least one of the disease activity indices (DAI) were performed in 48.8% and 87.3% of the visits, respectively. The indices assessed were RAI (45.4%), SDAI (28.6%), CDAI (39.1%), DAS (51.2%) and DAS28 (81.4%). The median (IQR) number of HAQ and DAI (at least one) assessment per year were 1.0 (0.2-2.5) and 2.6 (1.6-4.1), respectively. Table 1B shows the % of patients in remission, patients with low disease activity and patients with low HAQ. <h3>Conclusions</h3> In patients with RA, the assessment of disease activity, mostly by DAS28, is performed in the majority of the visits included in METEOR. The majority of proposed QIs could be assessed in the database indicating the feasibility of this set of QIs. <h3>Disclosure of Interest</h3> None Declared
Pain management was the subject of a special issue of JAMA last week: Treatment for depression improves pain in elderly patients
Authors: Janice Hopkins Tanne
Journal: BMJ (2003)

Treating elderly patients for their depression can reduce their pain and disability from arthritis, finds a randomised controlled trial of 1801 elderly patients with depression in five western US states (JAMA 2003;290: 2428-34 [PubMed]).

Of the patients, who were aged over 60 years, 1001 (56%) had arthritis as well as depression. They were randomly assigned to usual care or to treatment for depression with antidepressants or six to eight sessions of psychotherapy.

At follow up at three, six, and 12 months all the patients who were treated for depression said they had less functional impairment, better health, and better quality of life.

Dr Elizabeth Lin, of the Center for Health Studies at the Group Health Cooperative, Seattle, who coordinated the study, said that before entering the study “patients had significant pain, but few were taking pain medications or antidepressants.”

“Depression treatment was doubly effective,” she said. “Most patients had other chronic diseases, and depression leads to less compliance with medication regimens. Better depression care reduced depression, reduced pain severity, and increased the quality of life.”

Treatment for depression probably also reduced healthcare costs, she said, because depressed people use health care 50% more than people without depression.
AB0416 Bone Mineral Density and Bone Turnover Changes during Anti-TNFα Therapy in Rheumatoid Arthritis Patients
Authors: S. Tomkova, Z. Kmecova, Z. Killinger, P. Vanuga, M. Kuzma, L. Sterancakova, J. Payer
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> It is well-known that patients with chronic inflammatory diseases have more bone loss and a higher risk of fractures compared to general population. The causes of bone loss in inflammatory disorders are multiple. Recent studies suggest that inflammation in RA is a main contributor. Use of medications associated with osteoporosis and physical inactivity may play an important role too. On the other side anti TNFα therapy can control inflammation and may have a positive effect on bone health. <h3>Objectives</h3> To examine the effect of anti-TNF α blockers on bone mineral density and bone turnover in patients with severe, active rheumatoid arthritis (RA). <h3>Methods</h3> The 12-month prospective study enrolled 48 patients (36 postmenopausal women, 12 men, mean age 56.2 years, range 47–68 years,) with severe, active rheumatoid arthritis (DAS 28 score above 5.1) and decreased bone mineral density (BMD was in osteopenic range according to WHO classification). In all patients anti TNF treatment was initiated (adalimumab 22, etanercept 17 and certolizumab pegol 9 pts.). None of the patients was on antiporotic treatment (except calcium and vitamin D) and patients with changes in corticosteroid, use more than ±2,5mg of prednisolon, were not enrolled. BMD measurements of the total hip and lumbar spine were performed using dual-energy X-ray absorptiometry before the treatment and 12 months after the treatment. Bone turnover markers (BTM) osteocalcin (OC) and C-terminal telopeptide of collagen type I (CTx) were evaluated at the same time. <h3>Results</h3> BMD changes at the femoral neck and lumbar spine between baseline and 12 months after treatment were not statistically significant (0.896±0.124g/cm <sup>2</sup> versus 0.890±0.133 g/cm<sup>2</sup> and 0,978±0.139g/cm<sup>2</sup> vs 0,986±0.145g/cm<sup>2</sup> respectively), but a trend for BMD increase (+1.0%) at the lumbar spine was observed. Significant increase (<i>P</i> &lt;0.001) in osteocalcin levels (mean 21,124±7,10 before treatment and 27,35±8,17 after the treatment) and significant decrease (<i>P</i> &lt;0.001) of CTx (438,40±188 vs 330,93±142,11) was observed. Paired Student9s t-test was used for statistical analysis. <h3>Conclusions</h3> Our findings suggest that anti-TNF therapy may have a positive (uncoupling) effect on bone turnover markers and maintain stable BMD in such a high risk group of patients with severe RA. Stable dose of prednisolone during the study diminished the influence of corticosteroids on final results. Long-term use of TNF α blockers in RA might be therefore associated with an increase in bone strength, and fractures reduction. Properly controlled long-term trials are needed to fully evaluate the supposed antifracture efficacy of TNF blockade. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.5197
Abstract 4854: Mutations activating proliferation pathways in ovarian cancer
Authors: Nancy A. Uhrhammer, Yannick Bidet, Gautier Chene, Sandrine Viala, Yves Communal, Inès Raoelfils, Frédérique Penault-Llorca, Yves-Jean Bignon
Journal: Cancer Research (2011)

Abstract Ovarian malignancies may arise through different mechanisms of oncogenesis, which influence their treatment and are important for prognosis. Essential to carcinogenesis is the activation of proliferation pathways such as those directed by PI3 kinase or KRAS. New sequencing technologies may improve the detection of somatic mutations in tumor tissue, which is complicated by the low representation of a mutation within a tissue sample inevitably containing normal cells and subpopulations of malignant cells. We analyzed selected exons in PIK3CA, PIK3R, KRAS, BRAF, EGFR and ERBB2 in 34 primary malignant ovarian tumors, including 10 serous, 4 borderline, 11 endometrioid, and 9 mixed or rare subtypes. DNA was extracted from flash-frozen tumor tissues, amplified, and sequenced on a 454-GS-Flx Genome Sequencer. Expression of PTEN, p53, Bcl2, ALDH and Ki67 were assessed by immunohistochemistry on formalin-fixed tissues. Nine mutations were observed in PIK3CA, 5 in BRAF, 4 in KRAS, and 2 in EGFR. SNPs present in the amplicons analyzed allowed allelic imbalance to be estimated, showing possible amplification of EGFR in 9 of 20 informative samples, and of PIK3CA in 6 of 19 informative samples, none of which contained a point mutation. Endometrioid tumors frequently showed anomalies in PIK3CA, Bcl2 expression, and not p53 overexpression. P53 overexpression was typical of serous tumors, and was associated with the absence of mutations in any of the genes sequenced. Borderline and low grade tumors were characterized by BRAF mutation, no imbalance at EGFR, no anomalies at PIK3CA, and less frequent p53 overexpression. The absence of BRAF mutations in high grade tumors suggested that they do not evolve from borderline tumors. PIK3CA mutations were not mutually exclusive with KRAS mutations, confirming the non-redundancy of these intertwined signaling pathways. PTEN extinction was not significantly negatively associated with either point mutations or allelic imbalance at PIK3CA, consistent with different roles for PTEN loss and PI3-kinase activation at different stages of tumorogenesis, in spite of the close association of PTEN with the PI3-kinase pathway. No significant associations were observed between ALDH and Ki67 and any parameters measured. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4854. doi:10.1158/1538-7445.AM2011-4854
Abstract 3143: Epigenetic regulation of PTEN by miR-185 and miR-200b in liver cancer
Authors: Ximena V. Qadir, Chang Han, Tong Wu
Journal: Cancer Research (2012)

Abstract PTEN is one of the most commonly lost tumor suppressors in human cancers. Deletion of PTEN in mice has been shown to induce steatohepatitis and the development of primary liver cancers (hepatocellular carcinoma and cholangiocarcinoma). This study provides novel evidence for epigenetic regulation of PTEN in both hepatocellular carcinoma and cholagniocarcinoma cells. Treatment of the hepatocellular carcinoma cell line (Huh-7) and cholangiocarcinoma cells line (TFK-1) with the DNA methyltransferase (DNMT) inhibitor, Decitabine (1 mM), and the histone deacetylase inhibitor, Trichostatin A (TSA, 10mM), increased the expression of PTEN protein. Methylation specific qPCR assay shows that Decitabine/TSA treatment significantly reduced the methylation of the CpG islands located at the PTEN gene promoter. Furthermore, we have shown that miR-185 and miR-200b target DNMT-1 and -3A/3B, respectively, thus upregulating the expression of PTEN in hepatic cancer cells. Forced overexpression of miR-185 or treatment with mimic miR-185 abolished the expression of DNMT1 protein and enhanced the level of PTEN protein in both Huh-7 and TFK-1 cells. Accordingly, miR-200b overexpression or mimic treatment significantly decreased DNMT3A and DNMT3B protein levels and enhanced the expression of PTEN. These results demonstrate a novel epigenetic regulation of PTEN by miR-185 and -200b which is critical in hepatic carcinogenesis 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 3143. doi:1538-7445.AM2012-3143
Abstract P2-04-04: Prolactin cooperates with loss of p53 to promote mammary tumorigenesis.
Authors: KA O'Leary, R Sullivan, DE Rugowski, LA Schuler
Journal: Cancer Research (2012)

Abstract Prolactin (PRL) is critical for mammary development and lactation. Epidemiological studies also support a role for PRL in breast cancer. In order to study the contributions of PRL to tumor development and progression, we developed a transgenic mouse model that expresses PRL in the mammary epithelial cells (NRL-PRL), mimicking the mammary PRL production in women. Loss of function of the tumor suppressor p53 is a common occurrence in many human cancers including breast tumors. Interactions between PRL and p53 were examined by crossing the NRL-PRL mouse to p53 knockout mice which were made congenic on the FVB/N background. To circumvent the problem that p53−/− mice are prone to multiple nonmammary tumors, mammary cells from 10–12 week old wild-type, NRL-PRL, p53−/−, and NRL-PRL/ p53−/− were transplanted to wild type mammary glands. Histological analysis of the donor glands showed that NRL-PRL glands displayed marked epithelial proliferation and focally dilated ducts, whereas p53−/− glands exhibited irregular ductal epithelium with increased stromal density compared to wild type mice. In contrast, glands of donor PRL/ p53−/− females showed widespread epithelial hyperplasias and highly irregular ductal epithelium often surrounded by dense stroma. By one year of age, no tumors had developed from either wild-type or NRL-PRL transplanted epithelium. However, recipients of either p53−/− or NRL-PRL/ p53−/− mammary epithelium developed histologically similar anaplastic carcinomas. The presence of transgenic PRL decreased tumor latency (205 vs 244 days) and significantly increased tumor cell proliferation. In addition, these carcinomas appeared to be more aggressive: 5/16 (32%) of the NRL-PRL/ p53−/− tumors invaded into the peritoneal cavity, compared to 0/10 p53−/− tumors. Expression of matrix metalloproteinase 9 (MMP-9), but not MMP-2, was found to be significantly higher in the NRL-PRL/ p53−/−, compared to p53−/− tumors. MMP-9 is regulated by the transcription factor, AP-1, and PRL can signal through AP-1. NRL-PRL/ p53−/− tumors displayed significantly increased expression of the AP-1 family members, c-Jun and FosL, but not JunD or c-Fos compared to tumors from p53−/− mice. In addition, levels of c-Jun and FosL proteins increased in a similar pattern. In summary, interactions between PRL and loss of p53 promote breast cancer by increasing proliferation and invasiveness, potentially via AP-1 target genes. Supported by CDMRP BC053412. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-04-04.
Abstract 1065: IL-6 and IGF-1 receptor signal in stemness expression of HBV-related hepatocellular carcinoma .
Authors: Te-Sheng Chang, Thai-Yen Ling, Yu-Chih Wu, Wei-Chi Su, Jaw-Ching Wu, Ching-Chi Chi, Pey-Jium Chang, Jui-Hung Chang, Ya-Ting Yang, Kam-Fai Lee, Jun-Jen Liu, Shui-Yi Tung, Yen-Hua Huang, Liang-Mou Kuo, Hong-Nerng Ho, Yen-Hua Huang
Journal: Cancer Research (2013)

Abstract Expression of cancer stemness in hepatocellular carcinoma (HCC) is linked to drug resistance and tumor relapse which challenge the current therapy. However, mechanisms underlying the regulation of cancer stemness in HCC remain unclear. Effects of interleukin (IL)-6 and insulin-like growth factor I (IGF-I) on stemness expression in HCC were examined using OCT4/NANOG promoter luciferase reporter assays, RNA interference, secondary sphere formation, side population assay, and a xenograft animal model. Western blot analysis and immunohistochemical staining were used to detect the expression of OCT4/NANOG and phospho-IGF-I receptor (p-IGF-IR) in tissues. Levels of OCT4/NANOG and IGF-IR expressions were analyzed by real-time quantitative reverse transcriptase polymerase chain reaction (qPCR) and their association with tumor recurrence of hepatectomized HCC patients (n = 119) was determined using a Kaplan-Meier survival analysis. A high positive correlation between OCT4/NANOG and IGF-IR/p-IGF-IR expressions in human HCC tissues was observed. The concurrent expression of OCT4/NANOG/IGF-IR was mostly confined to HBV-related HCC (HBV-HCC) and was significantly associated with early tumor recurrence. Investigation of the underlying mechanism showed that IL-6 stimulated the autocrinal IGF-I/IGF-IR expression in a STAT dependent manner, and IGF-I/IGF-IR activation promoted the expression of stemness-related properties of Hep3B cells in both cell lines and xenograft murine models. IL-6 stimulated the expression of stemness-related properties in Hep3B cells, and inhibition of IGF-IR activation significantly suppressed the IL-6’s effects both in vitro and in vivo. Conclusions: Expression of OCT4/NANOG is regulated by IL-6-mediated IGF/IGF-IR signaling in HBV-HCC and is associated with the early recurrence of HCC. Citation Format: Te-Sheng Chang, Thai-Yen Ling, Yu-Chih Wu, Wei-Chi Su, Jaw-Ching Wu, Ching-Chi Chi, Pey-Jium Chang, Jui-Hung Chang, Ya-Ting Yang, Kam-Fai Lee, Jun-Jen Liu, Shui-Yi Tung, Yen-Hua Huang, Liang-Mou Kuo, Hong-Nerng Ho, Yen-Hua Huang. IL-6 and IGF-1 receptor signal in stemness expression of HBV-related hepatocellular carcinoma . [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1065. doi:10.1158/1538-7445.AM2013-1065
Abstract 3299: Salmonella commensal subspecies: a new model for the treatment of human cancer.
Authors: Vy Khan Ly, Edward Viloria, Priyanka Saxena, Bossakara Sokhom, Michael McClelland, Nabil Arrach
Journal: Cancer Research (2013)

Abstract Salmonella can colonize and survive in both hypoxic and oxygenated regions of solid tumors. Avirulent Salmonella mutants have been investigated as anticancer agents in human clinical trials. The strains used, derived from Salmonella enterica subspecies I (sspI) strains, proved to be highly toxic. Salmonella non-subspecies I (nsspI) strains are known as commensals of cold-blooded species and rarely cause disease in humans. Therefore, nsspI strains could present a safer alternative for the treatment of human cancer. Here, we explore the potential of nsspI strains for use as an anticancer therapy. Strains representing the five nsspI subspecies were tested for virulence and tumor targeting in mice, and for their ability to invade and kill human breast, prostate, and colorectal cancer cell lines. We identified nsspI strains that were successful at tumor targeting and capable of invading and killing a variety of cancer cell lines in vitro while being incapable of causing disease in mice. The nsspI strains were engineered to express two key therapeutic enzymes: cytosine deaminase and uracil phosphoribosyltransferase. After invading cancer cells in culture, intracellular bacteria from all five nsspI classes caused significant cytotoxicity in the presence of 5-FC. We conclude that nsspI strains could serve as potential improved anticancer vectors, to be used in combination with a therapeutic gene, for the treatment of primary or metastatic tumors. Due to their safety profile, nsspI strains present an excellent alternative to conventional Salmonella sspI strains for the treatment of human cancer. Citation Format: Vy Khan Ly, Edward Viloria, Priyanka Saxena, Bossakara Sokhom, Michael McClelland, Nabil Arrach. Salmonella commensal subspecies: a new model for the treatment of human cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3299. doi:10.1158/1538-7445.AM2013-3299 Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.
Blood Ammonia Concentration and Bromsulfalein Retention in Upper Gastrointestinal Hemorrhage
Authors: Gerald A. Belkin, Harold O. Conn
Journal: New England Journal of Medicine (1959)

THE localization of the site of upper gastrointestinal hemorrhage is frequently difficult and cannot always be established on clinical grounds. For several years bromsulfalein has served as a useful diagnostic test to differentiate cirrhotic and noncirrhotic patients with gastrointestinal bleeding.1 Recently, the blood ammonia concentration has been reported to be even more valuable in making this differentiation.2 , 3 The rationale for this determination is based on the fact that blood, like other nitrogenous substances in the alimentary tract, undergoes bacterial enzymatic degradation during which ammonia is liberated.4 , 5 In patients without hepatic disease the ammonia is removed from the circulation as the . . .
The Impact of Electromagnetic Navigational Bronchoscopy on a Multidisciplinary Thoracic Oncology Program
Authors: Craig Brown, Sharon Ben-Or, Paul Walker, Mark Bowling
Journal: Journal of the National Comprehensive Cancer Network (2016)

The Leo W. Jenkins Cancer Clinic has adopted a programmatic, multidisciplinary approach to thoracic tumors, which has involved the implementation of new therapeutic and diagnostic approaches. In 2012 we began using electromagnetic navigational bronchoscopy (ENB) as a new diagnostic tool. ENB uses a guidance system that combines CT imaging with magnetic field-guided spatial information to allow tissue sampling or placement of fiducial markers to guide radiation therapy.The numbers of early-stage (I and II) and late-stage (III and IV) lung cancers were compared before and after the introduction of ENB. We also examined the number of cases of fiducial marker placement using bronchoscopy versus interventional radiology before and after ENB was introduced. Fisher's exact test was used to compare the early- versus late-stage lung cancers found at diagnosis pre- and post-ENB introduction, fiducial marker placements using interventional radiology versus bronchoscopy pre- and post-ENB introduction, and pneumothorax rates.More early-stage cancers were diagnosed after ENB introduction (67 of 286 cases vs 116 of 290; P<.0001). Bronchoscopy was also used more frequently to place fiducial markers post-ENB (53 of 86 pre-ENB vs 105 of 117 post-ENB; P<.0001) and had a lower pneumothorax rate (4% vs 22%) than fiducial placement in interventional radiology (P<.001).The addition of ENB to a multidisciplinary thoracic oncology program may permit the diagnosis of lung cancer at an earlier stage and offers the ability to safely place fiducial markers for therapeutic purposes, such as radiation therapy, within the same procedure, potentially improving safety and decreasing time to treatment.