tbuckley/cabot-search huggingface dataset:
Ulcerative proctitis is a frequent location of paediatric-onset UC and not a minor disease: a population-based study
Authors: A Hochart, C Gower-Rousseau, H Sarter, M Fumery, D Ley, C Spyckerelle, L Peyrin-Biroulet, J-E Laberenne, F Vasseur, G Savoye, D Turck
Journal: Gut (2016)

<h3>Objective</h3> Natural history of paediatric-onset ulcerative proctitis (UP) is poorly described. Our aim was to describe the phenotype and disease course of incident UP in a population-based study of paediatric-onset UC. <h3>Patients and methods</h3> All patients with UC diagnosed &lt;17 years from 1988 to 2004, and followed during &gt;2 years have been extracted from a population-based registry. UC location was defined according to the Paris classification. Cumulative risks for use of immunosuppressants (IS), anti-tumour necrosis factor alpha (TNF-α) therapy, colonic extension and colectomy were described using Kaplan-Meier method. Risk factors for colonic extension were assessed using Cox proportional hazards models. <h3>Results</h3> 158 patients with paediatric-onset UC (91 females) with a median age at diagnosis of 14.5 years (Q1: 11.4–Q3: 16.1) have been identified and followed during a median of 11.4 years (8.2–15.8). Among them, 25% had UP (E1) at diagnosis and 49% of them presented a colonic extension at maximal follow-up. In these children, the cumulative risk for colonic extension was 10% at 1 year, 45% at 5 years and 52% at 10 years. No parameter at diagnosis was associated with colonic extension in the UP (E1 group). IS use was significantly lower in patients with UP than in those with E2, E3 or E4 location (p=0.049). For the UP cohort, the cumulative risk for colectomy was 3% at 1 year, 10% at 5 years, 13% at 10 years and 13% at 15 years. Risks for colonic extension, treatment with anti-TNF-α and colectomy did not differ between the E1 group and the E2–E3–E4 group. <h3>Conclusions</h3> UP is frequent in paediatric-onset UC and should not be considered as a minor disease. Compared with more extensive UC locations, risks for colonic extension, anti-TNF-α therapy and colectomy were similar in UP, whereas the risk for use of IM was lower.
Prescription drug misuse in Europe is higher than previously thought
Authors: Jacqui Wise
Journal: BMJ (2016)

Misuse of prescription drugs is a bigger problem in Europe than previously thought, research published in the open access journal BMC Psychiatry has shown.1

Non-medical prescription drug use is a leading public health issue in the United States, where an estimated 20% of people have at some time used a prescription medicine that was not prescribed to them or have used a prescription drug to achieve a euphoric state. However, until now the prevalence in Europe has been unclear.

The study looked at non-medical prescription drug use in 22 070 …
Btg1-Deficiency Promotes ETV6-RUNX1-Mediated Leukemic Transformation By Upregulation of BCL6
Authors: Esther Tijchon, Liesbeth van Emst, Dorette van Ingen Schenau, Laurens T van der Meer, Simone de Rijk, Owen Williams, Peter M Hoogerbrugge, Blanca Scheijen, Frank N. van Leeuwen
Journal: Blood (2014)
Bevacizumab plus paclitaxel versus bevacizumab plus capecitabine as first-line treatment for HER2-negative metastatic breast cancer (TURANDOT): primary endpoint results of a randomised, open-label, non-inferiority, phase 3 trial
Authors: Christoph Zielinski, István Láng, Moshe Inbar, Zsuzsanna Kahán, Richard Greil, Semir Beslija, Salomon M Stemmer, Zanete Zvirbule, Günther G Steger, Bohuslav Melichar, Tadeusz Pienkowski, Daniela Sirbu, Luboš Petruzelka, Alexandru Eniu, Bella Nisenbaum, Magdalena Dank, Rodica Anghel, Diethelm Messinger, Thomas Brodowicz
Journal: The Lancet Oncology (2016)
Comparison of response rate of advanced non-small lung cancer patients to liposomal cisplatin versus cisplatin both combined with paclitaxel: A phase III trial.
Authors: G. Stathopoulos, D. Antoniou, J. Dimitroulis, J. Stathopoulos, K. Marosis, P. Michalopoulou
Journal: Journal of Clinical Oncology (2010)

7579 Background: Liposomal cisplatin (Lipoplatin) was formed from cisplatin and liposomes composed of dipalmitoyl phosfatidyl glycerol (CPPG) soyphosphatidyl choline (5PC-3) cholesterol and methoxypolythylene glycol. It was developed to reduce the systemic toxicity of cisplatin and in particular nephrotoxicity. It has been already used in combination with other agents in pancreatic cancers, head and neck cancer and NSCLC. The present study had the objective to compare the effectiveness of lipoplatin combined with paclitaxel versus cisplatin with paclitaxel in advanced adenocarcinomas plus undifferentiated (nonhistological classified) of the lungs. Methods: From 2007-2009 152 patients with adenocarcinoma of the lungs and also undifferentiated carcinomas were recruited. Divided in two Arms – Arm A to be treated with liposomal cisplatin 200 mg/m2 combined with paclitaxel 135 mg/m2 and Arm B to be treated with cisplatin 75 mg/m2 combined also with paclitaxel 135 mg/m2 repeated every 2 weeks. Stage IIIB were 42 versus 40 and stage IV 37 versus 33 groups A and B respectively. Response rate was 59.49% of Arm A patients (lipoplatin group) and 42.47% of Arm B (cisplatin group). The difference was statistically significant. p-value 0.036. No difference in stable disease was seen between the two Arms. The median survival time in months between the two arms was for Arm A 10 months and for Arm B 8 months, p-value 0.6822. After 18 months the number of surviving patients was double for Arm A versus Arm B. Liposomal cisplatin in combination with paclitaxel produces statistical significantly higher response rate than cisplatin combined with paclitaxel in adenocarcinomas and undifferentiated inoperable carcinomas of the lungs. No significant financial relationships to disclose.
MYD88 L265P Mutation Is a Possible Unfavorable Prognostic Factor in Patients with Diffuse B-Cell Lymphoma
Authors: Anna A. Sidorova, Eugene E. Zvonkov, Andrey B. Sudarikov, Nataliya A. Severina, Alla M. Kovrigina, Vera V. Troitskaya, Valeri G. Savchenko
Journal: Blood (2015)
Abstract 3533: Role of autophagy-related protein expression in patients with rectal cancer treated with neoadjuvant chemoradiotherapy
Authors: Yoon Ho Ko, Soon Uk Hong, Der Sheng Sun, Hye Sung Won, Myung Ah Lee, Byoung Young Shim
Journal: Cancer Research (2016)

Abstract Background: Autophagy, a cellular degradation process, has complex roles in tumourigenesis and resistance to cancer treatment in humans. The aim of this study was to explore the expression levels of autophagy-related proteins in patients with rectal cancer and evaluate their clinical role in the neoadjuvant chemoradiotherapy setting. Methods: All specimens evaluated were obtained from 101 patients with colorectal cancer who had undergone neoadjuvant chemoradiotherapy and curative surgery. The primary outcomes measured were the expression levels of two autophagy-related proteins (microtubule-associated protein 1 light chain 3 beta (LC3β) and beclin-1) by immunohistochemistry and their association with clinicopathological parameters and patient survival. Results: Among the 101 patients, the frequency of high expression of beclin-1 was 31.7% (32/101) and that of LC3β was 46.5% (47/101). A pathologic complete response was inversely associated with LC3β expression (P = 0.003) and alterations in the expression of autophagy-related proteins (P = 0.046). In the multivariate analysis, however, autophagy-related protein expression did not show prognostic significance for relapse-free survival or overall survival. Conclusions: High expression of autophagy-related proteins shows a strong negative association with the efficacy of neoadjuvant chemoradiotherapy in patients with rectal cancer. Autophagy has clear implications as a therapeutic target with which to improve the efficacy of neoadjuvant chemoradiotherapy. Citation Format: Yoon Ho Ko, Soon Uk Hong, Der Sheng Sun, Hye Sung Won, Myung Ah Lee, Byoung Young Shim. Role of autophagy-related protein expression in patients with rectal cancer treated with neoadjuvant chemoradiotherapy. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3533.
Circulating cell-free DNA is elevated in community-acquired bacterial pneumonia and predicts short-term outcome
Authors: William W Siljan, Jan C Holter, Ståle H Nymo, Camilla Schjalm, Fredrik Müller, Pål A Jenum, Einar Husebye, Thor Ueland, Pål Aukrust, Tom E Mollnes, Lars Heggelund
Journal: Journal of Infection (2016)
Is gabapentin effective for preventing delayed nausea and vomiting (NV) after moderately and highly emetogenic chemotherapy (CT)?
Authors: A. Menendez-Leal, C. Quijano, A. G. Menendez-Rivera
Journal: Journal of Clinical Oncology (2006)

18575 Background: Following previous institutional observations,this protocol was designed to evaluate the efficacy of Gabapentin in the prophylaxis of delayed CT induced NV. Methods: The main elegibility criteria was moderate and severe NV on previous CT cycles.Gabapentin 300 mg caps. was given as follows: One capsule day -2, two capsules day -1 and one capsule tid from days 1 to 5. 24 pats. were evaluated; 22 (92%) female, 2 (8%) male.CT included Doxorubicin/Ciclofosfamide 15 (62.5%), Cis-Platin 5 (21%), Other regimens 4 (17%). Previous prophylaxis for all pats. included a 5-HT3 Antagonist plus Dexametasone. Pats. were instructed to complete a two-page Questionaire: On page 1 pats. indicated the intensity of nausea according a scale shown there. On page two they indicated the number of vomits they had.This was made three times daily for five days. The primary endpoint was reduction of NV aftyer CT. Results: The reduction observed in the number of vomits was as follows: Number of pats. that experienced 0 Vomits: day 1 (CT): 14 (58.3%); day 2: 18 (75%); day 3: 20 (83.3%); day 4: 18 (75%); day 5: 22 (91.7%). On the other hand, pats. that did not respond and had three or more vomits daily: day 1: 5 (20.8%); day 2: 2 (8.3%); day 3: 1 (4.2%); day 4: 3 (12.5%); day 5: 2 (8.3%).Most pats. experienced a decrease in the intensity of nausea as well. No significant side effects were seen. Conclusions: Gabapentin seems to have some efficacy preventing delayed NV after moderately and highly emetogenic CT. These results together with it’s possible effect on acute NV and good tolerability warrant further studies. No significant financial relationships to disclose.
Impact of gemcitabine + cisplatin + ipilimumab on circulating immune cells in patients (pts) with metastatic urothelial cancer (mUC).
Authors: Matt D. Galsky, Noah M. Hahn, Costantine Albany, Mark T. Fleming, Alexander Starodub, Przemyslaw Twardowski, Ralph J. Hauke, Guru Sonpavde, Miriam Merad, Sacha Gnjatic, Nina Bhardwaj, Uma Chippada-Venkata, William K. Oh, Seunghee Kim-Schulze
Journal: Journal of Clinical Oncology (2015)

4586 Background: Immune checkpoint blockade may play a role in the treatment of mUC. However, the role of CTLA4 blockade, the impact of chemotherapy on immune cell populations, and the optimal approach to combination regimens in pts with mUC remains poorly defined. An increase in tumor infiltrating and circulating CD4+ICOS+ cells after ipilimumab has been shown in pts with localized UC and correlated with improved outcomes in ipilimumab-treated melanoma pts (Carthon, Clin Can Res, 2010). Methods: Pts with mUC were enrolled on a phase 2 trial of chemotherapy + CTLA4 blockade. Patients received 2 cycles of gemcitabine + cisplatin (GC) followed by 4 cycles of GC + ipilimumab (GCI). Flow cytometry was performed on peripheral blood mononuclear cells at baseline, after GC, and after GCI to determine the impact of treatment on the frequency and phenotype of CD4+ and CD8+ T cells, regulatory T cells (CD4+CD25+CD127-CD45RA- Tregs), and myeloid-derived suppressor cells (CD13+CD14+CD11b+HLA-DR- MDSCs). Comparisons between time-points were made using Wilcoxon's rank test. Results: The trial has completed enrollment (n = 36) and flow cytometry data are available for the complete treatment sequence on 17 pts as of 2/2015 (Table). Conclusions: GC alone generally had no significant impact on the median % of circulating immune cell subsets though the increase in CD4+ICOS+ cells warrants confirmation. GCI resulted in an increase in CD4+ and CD8+ T cells, including the subset of CD4+ICOS+ cells, with a lesser increase in Tregs. The impact of individual changes in immune cell subsets on pt outcomes, and the role of GCI in mUC, will be further defined as efficacy data matures. Clinical trial information: NCT01524991.Impact of treatment on immune cell subsets (median % (IQR)). Baseline (BL) Post-GC Post-GCI p (GC v. BL) p (GCI v. GC) CD3+CD8+ 4.9% (8.3%) 4.0% (5.0%) 6.8% (10.1%) 0.2 0.04 CD8+ICOS+ 0.01% (0.4%) 0.05% (2.4%) 0.4% (3.7%) 0.2 0.9 CD8+PD1+ 0.02% (0.3%) 0.02% (0.2%) 0.02% (0.2%) 0.7 0.7 CD3+CD4+ 9.0% (7.4%) 5.0% (6.8%) 15.9% (11.2%) 0.7 0.001 CD4+ICOS+ 0.2% (0.7%) 0.5% (5.4%) 3.1% (8.9%) 0.03 0.04 CD4+PD1+ 0.1% (0.2%) 0.1% (0.3%) 0.4% (0.4%) 0.08 0.03 TReg 0.4% (0.6%) 0.4% (1.0%) 1.0% (0.9%) 0.5 0.04 MDSC 0.7% (3.8%) 0.4% (2.1%) 0.6% (6.7%) 0.6 0.6
Abstract 1530: Dissecting breast cancer dormant CTC phenotypes
Authors: Monika Vishnoi, Sirisha Peddibhotla, Wei Yin, Zhong Xue, Antonio T. Scamardo, Goldy C. George, David S. Hong, Dario Marchetti
Journal: Cancer Research (2016)

Abstract Tumor relapse is a clinically relevant problem in breast cancer where patients are asymptomatic because disseminated cells appear to become dormant for periods longer than 20 years and are undetectable by current clinical tools. Uncovering phenotypes of circulating tumor cells (CTCs) - the “seeds” of intractable metastasis-offers the promise to dissect CTC heterogeneity in relation to metastatic competence, to predict biomarker assessment, and to significantly improve monitoring and treatment of cancer. However, little is known about CTC biology and how CTCs differ in their capacity to circulate while maintaining a metastatic potential. We hypothesized that EpCAM-negative breast cancer CTC subsets exist, and avoid organ arrest with extreme efficiency by the concomitant presence of quiescence and stem cell properties. We collected peripheral blood of clinically diagnosed breast cancer patients with or without brain metastasis, and performed multiparametric flow cytometry to isolate EpCAM-negative CTC subsets with stem-cell properties (CD44+/CD24-), along with combinatorial expression of two neoplastic markers: urokinase plasminogen activator receptor (uPAR) and integrin beta1 (int β1). EpCAM-negative CTCs were further interrogated at a single-cell level employing DEPArray platform. Second, we were able to culture FACS-sorted CTC subsets, selected for six cell-surface expression markers (CD45-/EpCAM-negative/CD44+/CD24-/uPAR+/-/int β1+/-), as long-term in-vitro 3D CTC tumorspheres. Third, CTC subsets were interrogated for biomarker profiling and biological characteristics. We identified adhesive, proliferative and invasive properties of 3D CTC tumorspheres which were distinct per uPAR/int β1 combinatorial expression. Lastly, we performed next-generation whole-genome sequencing and mutation analyses to discover unique genomic signatures of uPAR/int β1 CTC subsets and verified as putative CTCs originally disseminated from primary breast tumor. Additional investigations are being pursued assessing the molecular and genomic characterization of uPAR/int β1 CTC subsets comprehensively. Clinical relevance of this research includes that this may enhance abilities to prospectively identify patients who may be at high-risk of developing breast cancer brain metastasis. Citation Format: Monika Vishnoi, Sirisha Peddibhotla, Wei Yin, Zhong Xue, Antonio T. Scamardo, Goldy C. George, David S. Hong, Dario Marchetti. Dissecting breast cancer dormant CTC phenotypes. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1530.
Abstract 1781: Ethnic disparity in pediatric leukemia relapse
Authors: Mirinda Gillespie, Greg Hale, Ernest K. Amankwah
Journal: Cancer Research (2016)

Abstract Background: Leukemia is the most prevalent pediatric malignancy, representing 25% of all cancer diagnoses among children. Despite recent substantial improvements in therapy that have dramatically increased survival, 10-20% of cases develop relapse and become refractory to treatment. Although racial/ethnic disparity in survival is well documented, limited knowledge currently exists on the disparity in relapse. The objective of this study was to compare the risk of pediatric leukemia relapse between Hispanic Whites and non-Hispanic Whites. Methods: The study included children (&amp;lt;21 years) diagnosed with leukemia between January 2006 and December 2014 at the All Children's Hospital Johns Hopkins Medicine, St. Petersburg, FL. Patients’ demographic and clinical information were obtained from an electronic health record-derived data warehouse. Ethnicity was self-reported. Leukemia diagnosis and relapse were identified using appropriate ICD-9 codes. Relapse-free survival was defined as the time from diagnosis to the first documentation of relapse. Hazard ratios (HR) and 95% confidence intervals (95% CI) for relapse-free survival were calculated using Cox proportional hazard models adjusting for age at diagnosis, gender and type of insurance (commercial vs government). Results: The study included 66 Hispanic Whites and 202 non-Hispanic Whites. The median age for both groups was 7 years. However compared to non-Hispanic Whites, Hispanic Whites were more likely to be males (59% vs 53%), to have government insurance (71% vs 35%) and had a shorter median follow up time (52 vs 66 months). Approximately 15% of Hispanic Whites developed relapse compared to only 5% non-Hispanic Whites. Kaplan-Meier survival analysis showed a difference in relapse between the two groups (log-rank p = 0.006). After adjusting for age at diagnosis, gender and type of insurance, Hispanic Whites were three times more likely to develop relapse compared to non-Hispanic Whites (HR = 3.1, 95%CI = 1.2-8.0, p = 0.02). Conclusion: Although the findings of this study suggest that ethnic disparity in pediatric leukemia may exist, our findings are limited by the inability to control for potential confounders such as medication adherence, timing of diagnosis, white blood cells at diagnosis and minimal residual disease. Future studies should further investigate this racial/ethnic disparity. Citation Format: Mirinda Gillespie, Greg Hale, Ernest K. Amankwah. Ethnic disparity in pediatric leukemia relapse. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1781.
Improving acute stroke services in the Netherlands
Authors: M. M. H. Lahr, D.-J. van der Zee, G.-J. Luijckx, P. C. A. J. Vroomen, E. Buskens
Journal: BMJ (2014)

Monks and colleagues report on England’s NHS business plan for hyperacute stroke care.1 A similar debate on the reorganisation of acute stroke services is ongoing in the Netherlands.

In 2013, the Health Care Insurance Board (CVZ, currently named National Health Care Institute (ZiNL)) published a nationwide quality vision on emergency healthcare.2 In 2010 a six month observational multicentre …
Abstract 2595: Texture variation on a mammogram and risk of breast cancer
Authors: Megan Rice, Kimberly Bertrand, John Heine, Bernard Rosner, Rulla Tamimi
Journal: Cancer Research (2016)

Abstract Mammographic density is one of the strongest risk factors for breast cancer. The most widely used measure of mammographic density is based on the percentage of dense tissue on a mammogram (percent mammographic density). However, there is additional information in mammographic images not captured by current mammographic density measurements including heterogeneity in patterns of breast density, often referred to as ‘texture’. More recent research suggests that textural features on a mammogram are associated with breast cancer risk independent of percent mammographic density. Therefore, we evaluated an automated measure called V, which measures the grayscale variation within a mammogram, in relation to subsequent breast cancer risk in 834 breast cancer cases (426 premenopausal and 408 postmenopausal) and 1805 controls (978 premenopausal and 827 postmenopausal) from a nested case-control study of breast cancer in the Nurses’ Health Studies (NHS). Among all women, V was modestly correlated with percent mammographic density (r = 0.48, p&amp;lt;0.01); this correlation did not vary substantially by menopausal status. Among premenopausal women, those in the highest quartile of V had a significantly higher risk of breast cancer (OR = 1.84, 95%CI: 1.30-2.61) compared to those in the lowest quartile. This association was similar, though more modest, among postmenopausal women (OR = 1.54, 95%CI: 1.08-2.19). These associations somewhat attenuated after adjustment for percent mammographic density in both premenopausal women (OR comparing extreme quartiles = 1.41, 95%CI: 0.97-2.03) and in postmenopausal women (OR comparing extreme quartiles = 1.21, 95%CI: 0.81-1.81). Future work will examine the associations between V and risk of breast cancer subtypes (e.g., by ER/PR tumor expression) as well as examine the associations between other measures of texture including markovian, run-length, laws, wavelet, fourier, and power features with breast cancer risk. Citation Format: Megan Rice, Kimberly Bertrand, John Heine, Bernard Rosner, Rulla Tamimi. Texture variation on a mammogram and risk of breast cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2595.