tbuckley/cabot-search huggingface dataset:
Alcohol abstinence in patients surviving an episode of alcoholic hepatitis: Prediction and impact on long‐term survival
Authors: José Altamirano, Hugo López‐Pelayo, Javier Michelena, Patricia D. Jones, Lluisa Ortega, Pere Ginès, Juan Caballería, Antoni Gual, Ramón Bataller, Anna Lligoña
Journal: Hepatology (2017)

Alcoholic hepatitis (AH) is the most severe form of alcoholic liver disease. Most studies have focused on short‐term prognosis, whereas factors associated with long‐term survival are largely unknown. The aims of our study were to (1) determine the impact of complete abstinence from alcohol on long‐term survival and (2) identify prognostic factors at admission capable of predicting abstinence during long‐term follow‐up in patients with AH. One hundred forty‐two patients with biopsy‐proven AH that survived the first episode were included. Demographic, psychiatric, and biochemical variables at admission and drinking status during follow‐up were obtained. Cox regression, logistic regression, and classification and regression trees (CART) analyses were used for statistical analysis. Overall mortality was 38% with a median follow‐up of 55 months. During follow‐up, complete abstinence was reported in 39% and was associated with better long‐term survival (hazard ratio, 0.53; P = 0.03). After adjustment for baseline prognostic scoring systems (Model for End‐Stage Liver Disease and age, bilirubin, international normalized ratio, creatinine scores), complete abstinence was independently associated with survival ( P &lt; 0.05). Age and lack of past alcoholism treatments were independently associated with complete abstinence ( P &lt; 0.001 and P = 0.02, respectively) during follow‐up. CART analysis generated a simple and practical algorithm based on the combination of past alcoholism treatments and age. Using CART analysis, we stratified 2 subgroups of patients with high (65%) and low (26%‐29%) rates of complete abstinence after an episode of AH. Conclusion: Complete abstinence after an episode of AH positively impacts long‐term survival. The combination of 2 variables easily obtained at admission might be useful to predict long‐term abstinence after an episode of AH. Strategies aimed at promoting alcohol abstinence in these patients are necessary. (H epatology 2017;66:1842–1853)
The potential clinical impact of pre-emptive screening of multiple polymorphisms in gene-encoding DPD on patients candidate for fluoropyrimidine based-chemotherapy: An experience of the Northern Italy Cancer Centre.
Authors: Francesco Iachetta, Angela Damato, Candida Bonelli, Alessandra Romagnani, Maria Banzi, Davide Nicoli, Enrico Farnetti, Bruno Casali, Carmine Pinto
Journal: Journal of Clinical Oncology (2017)

2567 Background: Dihydropyrimidine dehydrogenase (DPD) is a key enzyme in the metabolism of fluorouracil. Deleterious polymorphisms in gene-encoding DPD ( DPYD) results in a DPD deficiency that causes life-threatening toxicities when the standard dose of fluorouracil is used. DPYD*2A (IVS14+1G &gt; A) is the most common single-nucleotide polymorphism (SNP) associated with critical DPD deficiency. At present, most of the evidence supports screening for at least 3 SNPs (DPYD*2A, c.2846 A &gt; T, c.1679T &gt; G). The aim of this study is to confirm that the detection of additional polymorphisms of DPYD could enhance prevention of fluoropyrimidine toxicity. Methods: In 2011, we began to screen DPYD*2A in patients candidate for fluoropyrimidine based-chemotherapy. As the first step of the evaluation, we selected all cases of DPYD*2A wild type, from 2011 to 2012, who developed CTC-NCI-V.3 toxicity ≥ G3. In these patients, we researched the other 3 SNPs (c.2846 A &gt; T, c.1679T &gt; G, c.2194C &gt; A). Mutational status was analyzed with real Time PCR. Results: From 2011 to 2016 we pre-emptively screened DPD deficiency in 1,863 patients and 32 subjects (1.6%), with results mutated for DPYD*2A. As the first step of the evaluation, 548 subjects were assessed from 2011 to 2012. We found 7 patients who were carriers of the DPYD*2A mutation (1.27%). Of the 541 wild type cases, 114 presented toxicities ≥ G3. In this subgroup, 22 patients (19%) proved to be mutated for the other SNPs of DPYP, as reported in the table below. Conclusions: Preliminary data show that in 22 (19%) of 114 patients who presented severe toxicity which was not correlated with DPYD*2A, we found other polymorphisms of gene encoding DPD. Out of the 3 SNPs evaluated, c.2194 C &gt; A proved to be the most frequent, although it is the polymorphism that is least known and least studied. Such results suggest that the evaluation of additional polymorphisms could enhance the prevention of fluoropyrimidine toxicity. The results are expected to be clarified further in the second step, which is ongoing. [Table: see text]
Treat ER<sup>+</sup>ight: Treatment of Canadian postmenopausal women with ER<sup>+</sup> HER2<sup>-</sup> advanced breast cancer in the real-world setting with hormone therapy ± targeted therapy.
Authors: Nadia Califaretti, Nathaniel Bouganim, Susan Faye Dent, Catherine Doyle, Jan-Willem Henning, John S Sampalis, Sabrina R. Perri, Stephen K. L. Chia
Journal: Journal of Clinical Oncology (2016)

TPS614 Background: Although randomized controlled trials (RCTs) provide evidence of efficacy, generalization of these results to patients in the real-world setting is challenging, given RCTs are conducted in highly selected patient populations. An understanding of the effectiveness and safety of approved cancer therapies in routine clinical practice is essential in order to optimize the management of these patients and to identify treatment and safety gaps. Treat ER+ight is the first Canadian study to describe real-world treatment patterns/sequencing, effectiveness and safety for postmenopausal HR+HER2- advanced breast cancer (aBC) patients. Methods: This registry incorporates an observational prospective cohort design and will enroll 320 postmenopausal HR+HER2- aBC women that have been previously exposed to non-steroidal aromatase inhibitor (NSAI) therapy being treated with: endocrine therapy (ET) alone or ET in combination with targeted therapy (ET+TT). Patients who are receiving chemotherapy, have had > 3 lines of systemic treatment in the advanced setting or are participating in a randomized investigational trial will be excluded. All treatments, assessments and follow-up will be according to the treating physician’s judgment and practice, independent of the study; however, data collection schedule is as follows: ET+TT cohort: weeks 2, 4, 12 and every 12 weeks thereafter and ET cohort: 4 weeks and every 12 weeks thereafter. Once ET/ET+TT is terminated (for any reason), data is collected every 12 weeks up to 1 year. A subgroup of patients enrolled at select sites will undergo serial blood collections for ctDNA analysis as part of an optional exploratory biomarker sub-study. Outcome measures include treatment duration, adherence and sequence, prevention and management of treatment emergent adverse events, health care resource utilization, patient reported health-related quality-of-life (EORTC QLQ-C30 and – BR23), work-related productivity and survival status.
Identification of high risk basal like TNBC by an immunohistochemical approach.
Authors: Shilin N Shukla, Hemangini H Vora, Sonia K. Parikh
Journal: Journal of Clinical Oncology (2016)

e12571 Background: Triple negative breast cancer (TNBC) is a heterogeneous disease and constitutes two molecular subtypes basal like and non-basal like. Immunohistochemical criterion is most suitable to identify these molecular subtypes as non-basal like carry a more favorable prognosis and increased chemotherapy sensitivity. Methods: In forty eight (Stage II-A & B) TNBC, basal markers CK5/6, CK14, CK17, EGFR and Vimentin along with C-Kit were immunolocalised on formalin fixed paraffin embedded tissue sections. On tumor cells, marker negativity and focal positivity scored as negative, and 1+ ( < 10% cells positive), 2+ (10 to 50% cells positive) and 3+ ( > 50% cells positive) positivity scored as positive. The data was analysed by SPSS statistical software. Results: The combination of basal markers identified basal like phenotype in 39 (81.25%) and non-basal like phenotylpe in 9 (18.75% ) of TNBCs. The incidence of CK17 expression was higher (60%) followed by Vimentin (46%), EGFR (42%), CK5/6 (19%) and CK14 (06%) expression. In relation to clinicopathological parameters, a significant higher incidence of EGFR expression was noted in poorly differentiated tumors (P = 0.001). Ten patients (20.83%) developed distant metastases and of them eight had basal like phenotype and six were treated with CMF as adjuvant therapy. Further, C-Kit expression was noted in 50% of TNBC. None of the non basal TNBC expressed C-Kit while 62% of basal like TNBC expressed C-Kit (P = 0.003). Conclusions: A panel of basal marker may be evaluated routinely in breast pathology laboratories to identify high risk basal like TNBC.
From the Centers for Disease Control. Locally acquired neurocysticercosis
Journal: JAMA (1992)

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Origin, prevalence and response to therapy of hepatitis C virus genotype 2k/1b chimeras
Authors: Simone Susser, Julia Dietz, Bernhard Schlevogt, Eli Zuckerman, Mira Barak, Valeria Piazzolla, Anita Howe, Holger Hinrichsen, Sandra Passmann, Rasha Daniel, Markus Cornberg, Alessandra Mangia, Stefan Zeuzem, Christoph Sarrazin
Journal: Journal of Hepatology (2017)
Prognostic value of RANK – marker (receptor activator of nuclear factor - kB) in breast cancer carriers.
Authors: Sergey I. Zabroda, Elizaveta Maslyukova, Luiza Koritova, Oleg Korytov, Vladimir Odincov, Vladimir Sergeev, Svetlana Odincova, Grigoriy Raskin, Ekaterina Vlasova, Evgenii Obuhov, A Bondarenko
Journal: Journal of Clinical Oncology (2016)

e12540 Background: RANK is a transmembrane protein which expression has been initially found only in dendritic cells and mature osteoclasts. Soon the notice saying that a RANK-marker expression was found in the sound breast tissues and tumor cells of the prostate cancer and the breast cancer. Methods: 83 patients with the regional breast cancer (T2- 4N0-3M0) treated from 2003 to 2010 were enrolled. The criteria to become a part of the study were a histologically distinctive diagnosis of invasive breast cancer, aged 18 and older and ECOG 0 or 1. The immunohistochemical staining of the primary tumor received as a result of a biopsy was used for the test. The clinical material was studied retrospectively. Results: The analysis of dependence of time period till the development of metastases on the RANK expression has statistically proved the decrease of time period till the advance of the disease at high expression (RANK(high)) with patients as compared to the patients with low expression (RANK(low)). Similar regularity has been observed during studies of general survival rate. The survival rate of the patients whose RANK expression less than 5 % was statistically higher than in the group of patients with high RANK expression (higher than 5%). The plausibility of the differences between the survival curves was proved by the Gehan's Wilcoxon and Cox's F-Test. Conclusions: The determination of level of RANK in the breast cancer tumor cells gives an additional opportunity to forecast a breast cancer course (survival and time to progression). The special interest is a group of luminal cancer.
Endocrine therapy and chemotherapy in luminal metastatic breast cancer.
Authors: Marta Bonotto, Lorenzo Gerratana, Carmine De Angelis, Grazia Arpino, Donatella Iacono, Marika Cinausero, Gianpiero Fasola, Fabio Puglisi
Journal: Journal of Clinical Oncology (2015)

e11573 Background: Hormone receptor status is the only known predictive factor for response to endocrine therapy (ET). ET is a suitable option as 1st line therapy for hormone receptors (HRs) positive metastatic BC (MBC); nevertheless, chemotherapy (CT) is also used in some cases. Aim of the study is to evaluate the impact of 1stline treatment strategy on patients (pts) outcome and to analyze potential prognostic factors. Methods: The study cohort included 604 pts with Luminal MBC treated at University Hospitals of Naples and Udine, Italy, from 2004 to 2014. The cut off-point of 1% was used to define HRs positivity. Clinico-pathological factors were evaluated to test the association with outcome measures according to 1stline therapy. Hazard Ratio (HR) for OS and PFS was estimated through uni- and multi-variate Cox’s Proportional Hazard Regression model. Results: First line CT was chosen for 41.7% of pts. There was no difference between CT and ET at 1st line therapy for both OS (44.9 vs 40.1 months respectively, p = 0.07) and PFS (11.8 vs 9.7 months respectively, p = 0.15). At multivariate analysis, in pts treated with CT at 1stline, HER2 positivity (HR 0.49, 95%CI 0.25-0.98), Luminal B profile (HR 2.09, 95%CI 1.34-3.27) and BMI > 25 (HR 1.70, 95%CI 1.12-2.60) hold independent prognostic value in predicting for OS . Being ET naïve (HR 0.59, 95%CI 0.38-0.90) and > 70 year-old (HR 1.49, 95%CI 1.02-2.17) were independent prognostic factors for PFS. In ET treated pts, only visceral metastases (HR 1.80, 95%CI 1.23-2.64) had independent prognostic role for OS and Luminal B profile (HR 1.76, 95%CI 1.22-2.53) and being ET naïve (HR 0.66, 95%CI 0.45-0.97) were prognostic for PFS. Performance status was not an independent prognostic factor in neither the two groups. Conclusions: Inluminal MBC a similar outcome was observed between patients treated with ET compared to CT at 1st line. Notably, factors affecting outcome seem to differ according to treatment strategy.
CD4+ T cells memorize obesity and promote weight regain
Authors: Jianghuan Zou, Beibei Lai, Mingzhu Zheng, Qin Chen, Shujun Jiang, Anying Song, Zan Huang, Peiliang Shi, Xin Tu, Di Wang, Linrong Lu, Zhaoyu Lin, Xiang Gao
Journal: Cellular and Molecular Immunology (2017)

Body weight regain often causes failure of obesity therapies while the underlying mechanism remains largely unknown. In this study, we report that immune cells, especially CD4+ T cells, mediate the 'memory' of previous obese status. In a weight gain-loss-regain model, we found that C57BL/6J mice with an obesity history showed a much faster rate of body weight regain. This obesity memory could last for at least 2 months after previously obese mice were kept at the same body weight as non-obese mice. Surprisingly, such obesity memory was abrogated by dexamethasone treatment, whereas immunodeficient Rag1-/- and H2A-/- mice failed to establish such memory. Rag1-/- mice repossessed the obesity memory when immune cells or CD4+ T cells isolated from previously obese mice were transferred. Furthermore, depletion of CD4+ T cells led to obesity memory ablation. Taken together, we conclude that CD4+ T cells mediate obesity memory and promote weight regain.
Heartburn treatment in primary care
Authors: A. Williams
Journal: BMJ (2000)

# Prescribing omeprazole would conflict with desire to control prescribing costs {#article-title-2} EDITOR—Hatlebakk et al suggest that omeprazole 20 mg once daily should be considered as a first choice when patients with heartburn are being treated in primary care.1 With the formation of primary care groups all general practitioners are coming under increasing pressure to control prescribing costs. If costs are exceeded in one budget, budgets in other clinical areas (such as staff, including practice nurses) may be threatened. I and my colleagues in the practice have worked hard over two years to control our prescribing costs. Omeprazole was the largest single gastrointestinal drug cost, accounting for 7% of our total drug budget and just over half of our gastrointestinal drug costs. Hatlebakk et al make no mention of lifestyle advice—such as advice on smoking, diet, and weight reduction—as a method of controlling symptoms. Recent recommendations from our primary care group (through the primary care investment plan) suggest that we should target the use of proton pump inhibitors, and this will be linked to an element of payment that we receive under the prescribing incentive scheme. Increasingly we are using histamine receptor antagonists both as first line treatment of symptomatic reflux and as intermittent maintenance treatment. We are going to find considerable conflict in following Hatlebakk et al's recommendations.
Changes in 18F-FDG-PET/CT tumor metabolism and prediction of pathologic complete response rates after neoadjuvant chemotherapy in hormone-positive breast cancer.
Authors: Serap Kaya, Bilge Aktas, Eda Tanrikulu Simsek, Mehmet Akif Ozturk, Fuat Dede, Handan Kaya, Umit Mustafa Ugurlu, Zerrin Ozgen, Sinan Koca, Suleyman Halil, Rahib Hasanov, Ozkan Alan, Nalan Babacan, Faysal Dane, Mahmut Gumus, Fulden Perran Yumuk
Journal: Journal of Clinical Oncology (2016)

e12088 Background: Neoadjuvant chemotherapy (NAC) by reducing the tumor size provides higher operability and breast conserving surgery rate in locally advanced breast cancer (LABC) with an advantage to evaluate chemotherapy response. The aim of this study was to assess the predictive value of relative changes in standard uptake values (SUVmax) of 18F-FDG-PET/CT for pathologic complete response (pCR) after NAC in hormone-positive breast cancer. Methods: 90 hormone-positive LABC patients treated in Marmara University Pendik Research and Training Hospital Medical Oncology Clinics, Istanbul, Turkey between 2009 and 2015 was screened. Eligibility criteria were receiving histopathological verification of hormone–positive LABC, completed NAC (4-8 cycles) and evaluated for pCR postoperatively, and PET/CT scan was performed before and after NAC (anthracycline and/or taxanes-based plus trastuzumab if necessary). The relative changes of SUVmax both in primary tumor and axilla were determined and assessed for predicting pCR. Fiftyone patients were eligible for this retrospective analysis. Results: The median age was 46 years (26-76). Only 7 out of 51 patients (13.7%) had pCR and 44 (86.3%) patients had residual tumor. There was no significant difference between patients who had > 50% (n = 40) and < 50% (n = 11) SUVmax changes for predicting pCR rates (15% and 18% respectively) (p = 1.00). Four patients in HER-2 positive (n = 20) and 3 patients in HER-2 negative (n = 31) groups achieved pCR resulting in no association between HER-2 positivity and pCR rates (p = 0.296). Difference in Ki67 levels, tumor localization, menopausal status, grade, lymphovascular and perineural invasion were not found to be associated with pCR. Conclusions: SUVmax changes in later cycles of NAC as commonly practiced in oncology clinics was not found to be predictive for pCR in hormone-positive LABC. However, almost 80% of the patients had > 50% decrease in SUVmax and may still have a chance for more conservative surgery and less postoperative morbidity. As a result, 18F-FDG-PET/CT may still have a role to evaluate the tumor response with a need of larger studies and analysis for cost-effectivity .
Umbrella protocol for phase I/IIa trials of molecularly matched targeted therapies plus radiotherapy in patients with newly diagnosed glioblastoma without MGMT promoter methylation Neuro Master Match (N²M²).
Authors: Anne Hertenstein, David Jones, Felix Sahm, Elke Pfaff, Barbara Hutter, Irini Karapanagiotou-Schenkel, Andreas Eisenmenger, Matthias Osswald, Antje Wick, Sarah Loew, Martin Bendszus, Juergen Debus, Christel Herold-Mende, Andreas Unterberg, Andreas von Deimling, Benedikt Brors, Michael Platten, Stefan M. Pfister, Wolfgang Wick
Journal: Journal of Clinical Oncology (2016)

TPS2084 Background: Patients with newly diagnosed glioblastoma without O6-methyl guanine O6-methylatransferase (MGMT) promoter methylation do not benefit from alkylating therapy. Clinical trials aiming at replacing temozolomide (TMZ) with targeted agents in unselected patient populations have failed to demonstrate any benefit. Advances in the understanding of glioblastoma at a molecular level along with technological progress have led to the identification of key genetic alterations in a timely manner allowing for treatment decisions in newly diagnosed patients. In this setting, these alterations not only refine the sub-classification of glioblastoma, but also allow for subset specific treatments, with contemporary analyses allowing for differentiating prognostic and predictive biomarkers. Methods: N2M2 is an open label phase I/II umbrella trial for patients with newly diagnosed glioblastoma without MGMT promoter methylation to show safety, feasibility and preliminary efficacy (decision for future randomized phase II/III) of treatment with targeted compounds in addition to radiotherapy based on thorough molecular characterization. N2M2 is formally divided into a DISCOVERY and a TREATMENT aspect. DISCOVERY includes the use of panel, whole exome and transcriptome sequencing, methylome analysis using Illumina EPIC arrays, and gene expression arrays to find new, unexpected targets and get a comprehensive view on affected pathways, with dedicated bioinformatics evaluation (GUIDE), a Molecular Tumor Board and a timely initiation (≤ 4 weeks) of the postoperative treatment. Stratification for TREATMENT takes place in seven subtrials according to the best matching molecular alteration. For the phase I parts, a maximum of 9 patients will be enrolled in each cohort. A Bayesian criterion is used for continuous monitoring of toxicity. In the phase II trials, progression-free survival at six months is used as endpoint for efficacy. Patients with no matching alteration receive the standard chemoradiotherapy with TMZ and serve as contemporary, non-randomized controls with an estimated PFS6 of 40%.
Abstract 2200: Exaggerated Exercise Blood Pressure Response Is Accompanied by a State of Pronounced Inflammatory Activation, Impaired Thrombosis/Fibrinolysis System and Arterial Stiffening in Essential Hypertension
Authors: Kyriakos Dimitriadis, Costas Tsioufis, Eirini Andrikou, Maria Selima, Nikos Papamichail, Ioannis Giatrakos, Dimitris Tousoulis, Christodoulos Stefanadis
Journal: Circulation (2008)

There are conflicting data regarding the cardiovascular prognostic value of hypertensive response to exercise (HRE), while low-grade inflammation, arterial stiffness and impaired fibrinolysis are a...