tbuckley/cabot-search huggingface dataset:
Endoscopic ultrasonography Versus Helical Computed Tomography for Preoperative staging of Gastric Cancer
Authors: Y Cui
Journal: Endoscopy (2006)

Objective: To compare Endoscopic ultrasonography and Helical Computed Tomography in the TNM staging of gastric cancer and to assess the impact of changes in the TNM classification on the staging accuracy of these methods. Methods: Both EUS and HCT were performed in 43 patients with gastric cancer proved by biopsy, and the results of EUS and HCT were compared prospectively with surgical pathological findings. Results: The T-staging accuracy of EUS (71.7%) was similar to the accuracy of HCT (65.8%). N-staging accuracy of both methods was similar when the fourth edition of the TNM classification was used (EUS 76.3%; HCT 65.8%). When the fifth edition of the TNM classification was used, the N-staging accuracy of EUS (60.5%) was similar to the accuracy of HCT (63.2%), too. The sensitivity and specificity of EUS in M-staging were 30.0% and 96.4%, respectively. The sensitivity and specificity of HCT in M-staging were 80.0% and 92.9%, respectively. Conclusion: The accuracy of EUS and HCT in the TNM staging of gstric cancer are high, but they have limitations on accuracy of N2, N3-staging.
Efficacy and Safety of Corticosteroids for Persistent Acute Respiratory Distress Syndrome
Authors: Kenneth P Steinberg, Leonard D Hudson, Richard B Goodman, Catherine Lee Hough, Paul N Lanken, Robert Hyzy, B Taylor Thompson, Marek Ancukiewicz
Journal: New England Journal of Medicine (2006)

Persistent acute respiratory distress syndrome (ARDS) is characterized by excessive fibroproliferation, ongoing inflammation, prolonged mechanical ventilation, and a substantial risk of death. Because previous reports suggested that corticosteroids may improve survival, we performed a multicenter, randomized controlled trial of corticosteroids in patients with persistent ARDS.We randomly assigned 180 patients with ARDS of at least seven days' duration to receive either methylprednisolone or placebo in a double-blind fashion. The primary end point was mortality at 60 days. Secondary end points included the number of ventilator-free days and organ-failure-free days, biochemical markers of inflammation and fibroproliferation, and infectious complications.At 60 days, the hospital mortality rate was 28.6 percent in the placebo group (95 percent confidence interval, 20.3 to 38.6 percent) and 29.2 percent in the methylprednisolone group (95 percent confidence interval, 20.8 to 39.4 percent; P=1.0); at 180 days, the rates were 31.9 percent (95 percent confidence interval, 23.2 to 42.0 percent) and 31.5 percent (95 percent confidence interval, 22.8 to 41.7 percent; P=1.0), respectively. Methylprednisolone was associated with significantly increased 60- and 180-day mortality rates among patients enrolled at least 14 days after the onset of ARDS. Methylprednisolone increased the number of ventilator-free and shock-free days during the first 28 days in association with an improvement in oxygenation, respiratory-system compliance, and blood pressure with fewer days of vasopressor therapy. As compared with placebo, methylprednisolone did not increase the rate of infectious complications but was associated with a higher rate of neuromuscular weakness.These results do not support the routine use of methylprednisolone for persistent ARDS despite the improvement in cardiopulmonary physiology. In addition, starting methylprednisolone therapy more than two weeks after the onset of ARDS may increase the risk of death. (ClinicalTrials.gov number, NCT00295269.).
Abstract 5434: Development and biological characterization of novel, potent and stable isoform-specific inhibitors of histone deacetylase-8 (HDAC8)
Authors: Sriram Balasubramanian, Mint Sirisawad, Erik Verner, Chitra Mani, Purvi Jejurkar, Joseph J. Buggy
Journal: Cancer Research (2010)

Abstract Histone deacetylase (HDAC) inhibitors have shown promise for the treatment of hematological and solid tumors. The current clinical candidates all inhibit multiple isoforms of the 11-member zinc-dependent HDAC family. With a view to increasing disease specificity and decreasing toxicity, we have developed potent and selective inhibitors of one isoform, HDAC8. We have previously described one such molecule, PCI-34051, which inhibited HDAC8 with a Ki of 10 nM and greater than 200-fold selectivity over other HDAC isoforms. However, this compound displayed poor metabolic stability and was not suitable for in vivo testing in animal models. We have therefore developed a series of analogs to increase metabolic stability while maintaining potency and isoform selectivity. These compounds, which are based on different pharmacophores, have similar potency and selectivity to PCI-34051 but have increased cellular potency, inhibiting cell growth and inducing apoptosis with EC50 of ∼1-2 μM in Jurkat and Hut78 lymphoma cells. These compounds also showed increased metabolic stability in an in-vitro rat liver microsomal assay. Since increased HDAC8 expression has recently been shown to be correlated with poor survival in neuroblastoma, the biological activities of these novel HDAC8 inhibitors were tested in neuroblastoma cell lines. Interestingly, these compounds were found to inhibit cell growth and induce differentiation in neuroblastoma cells. However, incubation with higher concentrations of these compounds did induce caspase activation and apoptosis in these cells. In keeping with the HDAC8 selectivity, no tubulin or histone acetylation was observed at upto 25μM. The best of these inhibitors is currently being tested in mouse xenograft models of T-cell lymphoma as well as neuroblastoma and the results will be presented. 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 5434.
Case 21-1989
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, William F. McNeely, Betty U. McNeely, K.F. Rothman, M.J. Imber
Journal: New England Journal of Medicine (1989)

Presentation of CaseA newborn girl was admitted to the hospital because of respiratory distress, muscular hypotonia, and cutaneous vesicles.The child was born at full term by a normal spontaneous vaginal delivery and was the second child of a 29-year-old mother. The pregnancy was complicated by hyperemesis during the first trimester, which required hospital admission for rehydration; at four months of pregnancy a herpetic lesion on the mother's buttock yielded herpes simplex virus, Type II, on culture; no genital lesions were detected. Delivery occurred 1 1/2 hours after artificial rupture of membranes. The birth weight was 3.94 kg. At . . .
508 IS HBEAG LOSS ASSOCIATED WITH AN IMPROVED OUTCOME IN HEPATITIS B PATIENTS TREATED WITH TENOFOVIR DISOPROXIL FUMARATE (TDF)?
Authors: S. Fung, M. Buti, E. Gane, N. Afdhal, J. Flaherty, E. Martins, N. Bekele, J. Bornstein, P. Marcellin
Journal: Journal of Hepatology (2012)
A crusader with a sense of humour
Authors: K. Abbasi
Journal: BMJ (1998)

In his first year as president of the Royal College of Physicians of London, George Alberti is on a crusade of reform. Kamran Abbasi spoke to him

The Royal College of Physicians of London has been criticised for being stuck in the 19th century, but the new president, Professor George Alberti, is preparing to haul this highly esteemed, yet much criticised, institution into the new millennium.

When he moved into St Andrew's Place, Professor Alberti noticed that two essentials were missing from the president's office: a computer and a coffee machine. He quickly put that right and added a further ingredient of his own, a sense of humour. The next task was reform: “I never look back. I want to ensure that our fellows are aware that we are working for them, and that we are not just a comfortable little London club, but that we are a national college working for physicians, and all trainees as well. I feel that I was elected because I came from out there and was not a part of the establishment.”

His vision of the future is a modern college, in touch with the opinions of its members and fellows, taking the lead in promoting a high quality …
Abstract 1291: Tumor growth inhibitory effect in EIF4B silenced in vitro and in vivo lung cancer models
Authors: Jung-Young Shin, Xiang-Hua Zhang, Jeong-Oh Kim, Ji-Eun Oh, Hiun Suk Chae, Young Ae Joe, Jin-Hyoung Kang
Journal: Cancer Research (2012)

Abstract Backgraound The eIF4B, a key molecule for initiation of protein translation, play an important role in cell growth, proliferation and survival. We investigated that eIF4B is associated with the molecular mechanism of de novo resistance against EGFR TKIs and its role on cell proliferation and survival in NSCLC cells. Method Among five NSCLC cell lines harboring EGFR and K-RAS wild type, PC14 cells showing the highest IC50, were selected for our experiment. In eIF4B silenced PC14 cells by shRNA, we evaluated cell proliferation by direct cell counts and SRB assay and cell cycle distribution using flow cytometry. The expression of signal molecules, transcription factors and apoptosis associated proteins was measured by Western blot. In vivo tumor model established by subcutaneous injection of eIF4B silenced PC14 cells, the retardation of tumor growth was measured. Results In PC14 cells transformed with eIF4B shRNA, we observed the protein expression of eIF4B was reduced (&amp;gt;70% at day 5). The proliferation of eIF4B silenced cells was greatly inhibited both in vitro and in vivo tumor model. Between eIF4B silenced cells and control cells, there was no significant difference in anti-proliferative activity of several target inhibitors (enzastaurin, gefitinib, LY294002, vandetanib) against EGFR-PI3K-AKT signaling molecules. The expression of proteins involved in cell survival (pEGFR, pAKT and mTOR), transcription factors (pNFkB and TS) and anti-apoptotic protein (bcl-2), was decreased and apoptosis associated proteins (phospho-p53 and active caspase-3) were increased. The G0/G1 cell fraction in eIF4B silenced cells was reduced (47.3% vs. 55.1% in control cells) and accumulation of apoptotic cells was observed (12.7% vs. 1.5% in control cells; shown as sub G1 population). Conclusion Our results demonstrated that eIF4B silencing resulted in a marked decrease of several anti-apoptotic and pro-proliferative proteins and eIF4B was required for cell proliferation and survival by regulating cell cycle and cell signaling molecules. 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 1291. doi:1538-7445.AM2012-1291
PTU-083 Biliary Microrna Markers in Bile Aid the Diagnosis of Cholangiocarcinoma at ERCP
Authors: A Zabron, A Frampton, J Krell, J Stebbing, L Castellano, S Khan, L Jiao
Journal: Gut (2013)

<h3>Introduction</h3> Cholangiocarcinoma (CCA) is a primary biliary ductal cancer which is often difficult to diagnose and which carries a poor prognosis. New diagnostic tests are urgently needed to improve patient outcome. Bile is a rich source of potential novel biomarkers for CCA, due to its intimate proximity to the malignant lesion. However, there are no biliary biomarkers for CCA currently available. MicroRNAs (miRNAs) are key post-transcriptional regulators, and influence tumorogenesis. Studies on cell lines and tissue have identified several potential miRNA signatures for CCA, and recently miR-9 was identified as elevated in bile from CCA compared with benign disease<sup>1</sup>. In this study we aimed to measure specific miRNA expression in bile from patients with CCA, gallstone disease and pancreatic adenocarcinoma (PA) and to assess their performance in differentiating these causes of biliary obstruction. <h3>Methods</h3> Bile was collected at endoscopic retrograde cholangiopancreatography (ERCP) from patients with CCA (n = 6), PA (n = 10) and gallstones (n = 8; benign control). Bile was prepared as previously described1 and total RNA was isolated using TRIzol (Invitrogen, Paisley, UK). Quantitative real-time reverse-transcription polymerase chain reaction (RT-qPCR) was performed using Taqman mature miRNA primers and probes (Applied Biosystems, Cheshire, UK). Expression of oncomiR-21, miR-155 and miR-106a was measured. Cycle passing threshold (Ct) was recorded and normalised to RNU6B expression. Relative expression was calculated as 2Ct_miRNA-Ct_RNU6B. PCR reactions were carried out in duplicate. <h3>Results</h3> MiR-106a and oncomiR-21 were highly expressed in bile from patients with CCA compared to those with gallstones. MiR-155 was not significantly upregulated in malignancy. In discriminating CCA from benign disease, miR-106a had sensitivity and specificity of 83.3% [95% CI 36–100] and 88% [95% CI 47–100] respectively, with an AUC of 0.83 (cut-off level &gt; 6.05). OncomiR-21 was also upregulated in the bile of both tumour types, but was not as reliable. Neither miRNA discriminated significantly between PA and CCA. <h3>Conclusion</h3> MiRNA can be reliably isolated from bile pellets. Both miR-106a and oncomiR-21 are potential novel biliary biomarkers for CCA, and could improve differentiation of benign from malignant disease at ERCP. Further work is required to validate these findings in a larger cohort and against other disease groups, and to investigate possible correlations between miRNA profile and disease course. <h3>Disclosure of Interest</h3> None Declared <h3>Reference</h3> Shigehara K, Yokomuro S, Ishibashi O, <i>et al.</i> Real-time PCR-based analysis of the human bile microRNAome identifies miR-9 as a potential diagnostic biomarker for biliary tract cancer. <i>PloS one</i><i>.</i> 2011; 6(8):e23584.
SAT0411 Gender Differences in Disease Activity in A Psoriatic Arthritis Routine Care Cohort: Table 1.
Authors: S.M. Reddy, J.U. Scher, C.J. Swearingen, Y. Yazici
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Randomized clinical trials (RCT) provide information about efficacy of various agents typically in a controlled, detailed setting. Routine care cohorts, conversely, can add data about patient clinical phenotypes, treatment choices and responses in the 9real world9 to better inform the practicing rheumatologists. Studying the true impact of psoriatic arthritis (PsA) and the role of newly available treatment options for patients seen in routine clinical environment may help physicians care for these patients more effectively. <h3>Objectives</h3> To study patient characteristics, disease activity, treatment choices and responses in a routine care psoriatic arthritis cohort in a university setting. <h3>Methods</h3> New York University Psoriatic Arthritis Cohort (PAC) was established in 2005 as part of the Arthritis Registry Monitoring Database (ARMD) and has been following patients with PsA prospectively, with data collected as part of routine care. At each visit, clinical data is collected through MDHAQ (for function, pain, patient global assessment, fatigue, patient self report joint counts, physician global assessment), and 28 tender and swollen joint counts. In addition, medication history, demographic data and selected laboratory tests are also collected. We analyzed patient characteristics and medication use along with disease activity in our cohort. <h3>Results</h3> 497 patients were seen to date (48.5% female, mean age 49.6 yr, disease duration 11.9yr, years of education 16.4, White 64%, Black 1.6%, Hispanic 6.8%, Other 27.6%). No differences were noted between males and females. However, female patients with PsA had significantly worse function (2.0 vs 1.6, p=0.005), pain (4.9 vs 4.2, p=0.006), pt global (4.6 vs 3.7, p=0.001), RAPID 3 scores (11.6 vs 9.4, p=0.001), fatigue (4.6 vs 3.2, p&lt;0.001), and pt reported joint counts by RADAI (9.9 vs 7.9, p=0.017) compared to males with the disease. After adjusting for age and education; pain, patient global scores, RAPID3 scores, and fatigue remained significant. No differences in ESR and duration of morning stiffness were noted. Although CRP levels were overall lower in females, the values were not statistically significant (4.6 vs 9.9, p=0.060). No differences were noted in the proportion of patients treated with prednisone, DMARDs, biologics, or combination DMARD/Biologics among females and males (Table). <h3>Conclusions</h3> In this routine care cohort of almost 500 PsA patients, females had worse disease activity compared to males, despite receiving the same type of medication, both in monotherapy and in combination. The reasons for this seemingly undertreament among females needs further study. <h3>Disclosure of Interest</h3> S. Reddy *: None declared, J. Scher * Consultant for: Pfizer, Janssen, C. Swearingen: None declared, Y. Yazici Consultant for: Abbvie, BMS, Celgene, Genentech, Samumed, Pfizer, UCB <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.4964
175 CEREBRAL MYO-INOSITOL DECREASE BEFORE LIVER TRANSPLANTATION INDICATES HIGHER RISK FOR POST-TRANSPLANT ENCEPHALOPATHY
Authors: H. Pflugrad, P. Raab, M. Bernhardt, A. Goldbecker, H. Barg- Hock, C. Strassburg, K. Weissenborn, A.B. Tryc
Journal: Journal of Hepatology (2013)
Abstract P2-10-26: Association between circulating tumor cells and molecular breast cancer subtypes
Authors: N Gang, W Haibo, L Funian, L Chen, L Xiaoyi, W Xingang, L Zhidong
Journal: Cancer Research (2012)

Abstract Background and Objective: Circulating tumor cells (CTCs) provide crucial information for the management of breast cancer patients. CTCs analysis can be used as a liquid biopsy approach for prognostic and predictive purposes in breast and other cancers. Several contradictory results presented about the breast cancer subtypes of CTCs recently. The aim of this study was therefore to analysis the association between the CTCs and molecular breast cancer subtypes. Methods: Blood samples were obtained from 143 breast cancer patients admitted to Breast Surgery Department, Affiliated Hospital of Medical College, Qingdao University. CTCs were detected by using immunomagnetic enrichment and a commercial kit, based on RT-PCR, was used to characterize CTCs. The expression of ER, PR, HER2 was detected by immunohistochemistry. The molecular subtypes were defined as: luminal A (ER+ and/or PR+, HER2−), luminal B (ER+ and/or PR+, HER2+), TNBC (ER−, PR−, HER2−), and HER2+, (ER−, PR−, and HER2+). The relations between the positive rate of CTCs and clinicopathological characteristics of primary tumor and molecular subtypes of breast cancer patients were analyzed. Results: Overall positive rate of CTCs was 39.8% (57/143). The positive rate of CTCs in patients with Luminal A, Luminal B, HER2+ and TNBC subtype was 33.8% (26/77), 47.1% (8/17),50.0% (6/12) and 45.9%(17/37). There was significant difference in positive rate of CTCs by different molecular subtypes (P = 0.0415), especially at different AJCC stages (P = 0.004). The positive rate of CTCs in patients with Luminal A subtype was significantly lower than patients with the others breast cancer subtypes (p = 0.0387). Conclusion: Our study suggests that presence of CTCs was more frequently found in patients with HER2+ and Luminal B subtypes. The presence of CTCs in patients with TNBC subtype was not as high as we wished. Theoretically, the positive rate of CTCs in TNBC subtype should be higher than that of others subtypes for being more aggressive histologically features and having increased potential to be invasive. One possible explanation for this might because of lacking epithelial markers expression and epithelial-mesenchyme transition (EMT) characteristics, CTCs of TNBC subtype are missed when using the standard EpCAM-based method. Shortage of patient's number was another possible reason. Further research on the Association between CTCs and molecular breast cancer subtypes will contribute to a better understanding of the biology of metastatic development in cancer patients. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-10-26.
Abstract P1-10-08: Breast Reconstruction Surgery Following Mastectomy: Love or Money?
Authors: A Al-Allak, H Knight, C Walter, F Court, HY. Chan
Journal: Cancer Research (2010)

Abstract Introduction All women should be considered for breast reconstruction following mastectomy, providing they are medically fit. The proportion of women having a reconstruction varies significantly from centre to centre; a key reason for this is the availability of reconstruction in that centre. In countries with an insurance funded health care system, breast reconstruction may also be influenced by the ability to pay. In the UK, breast reconstruction is available for free on the National Health Service (NHS). The aim of our study was to identify any other factors that may influence a woman's decision to have a reconstruction. Methods All women having a mastectomy under the care of one breast surgeon between 2000 and 2010 were included. Data were collected retrospectively and included: age at surgery, marital status, dependents under 18, employment status, home circumstances and Zip code. The Index of Multiple deprivation (IMD2007) was derived for each patient from their zip code using the UK National Statistics data. The patients were divided into two main groups: those who underwent reconstruction and those who opted for mastectomy only. The Mann-Whitney U test was used to determine whether there was a statistical difference between the two patient groups using the statistical package R. Results A total of 272 patients underwent mastectomy during the study period, of these patients 148 had mastectomy only (median age 67, range 34 — 95) and 124 had a reconstruction (median age 51, range 28-73). When the two groups were compared statistical analysis revealed that the reconstruction group were younger (P&amp;lt;0.002), more likely to be married or have a partner (p=0.00065), have dependents (P&amp;lt;0.0005) and work (P&amp;lt;0.0005). There was no significant difference between the two groups socioeconomic status. Conclusion These data suggest that social and economical inequalities do not affect the decision making process for breast cancer patients in a society where health care is free at the point of delivery. However young age and a stable family/partner do. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P1-10-08.