tbuckley/cabot-search huggingface dataset:
Three versus six months adjuvant oxaliplatin plus fluoropyrimidine chemotherapy for patients with stage III colon cancer: The Hellenic Oncology Research Group (HORG) participation to the International Duration Evaluation of Adjuvant (IDEA) chemotherapy project.
Authors: John Souglakos, Ioannis Boukovinas, Spyros Xynogalos, Stylianos Kakolyris, Nikolaos Ziras, Michael Vaslamatzis, Alexandros Ardavanis, Athanasios Athanasiadis, Nikolaos E. M. Androulakis, Nikolaos K. Kentepozidis, Athina Christopoulou, Paris Makrantonakis, Ioannis I. Varthalitis, Charalampos Christofyllakis, Christos E. Emmanouilides, Dimitrios Mavroudis, Efthimios Prinarakis, Aggeliki Kalisperi, Dora Hatzidaki, Vassilis Georgoulias
Journal: Journal of Clinical Oncology (2018)

730 Background: The IDEA international collaboration aimed to combine data from 6 randomized trials to investigate whether a 3-month (3m) of oxaliplatin/fluoropyrimidines-based adjuvant chemotherapy (CT) is non-inferior to the 6-month(6m) for 3-year disease free survival (DFS)in stage III colon cancer (CC). Methods: HORG-IDEA randomized patients between 3Mand 6M of CT with mFOLFOX6 or CAPOX. DFS was estimated using the Kaplan–Meier method and described using 3 years DFS rate. Results: In total708 patients were randomized between May 2009 and October2015, 354in each arm. Among them the basic characteristics was: median age 63.9 years; mFOLFOX6: 41.8% and CAPOX 58.2%, N1: 74.9%, N2: 25.2%; T1-3: 86.4%, T4: 13.6%. DFS median follow-up was 54.2 months. There were 214 DFS events (109in 3M and 105 in 6M arm) leading to a 3-year DFS rate of 73.2% in the 3M vs. 74.9% in the 6M (HR = 1.03; 95%CI 0.80–1.43, p = 0.622).For patients receiving mFOLFOX6, 3-year DFS rate was 71.8% in the 3M vs.77.7% in the 6M (HR = 1.18; 95%CI 0.74–1.88 p = 0.478). For patients receiving CAPOX 3-year DFS rate was 74.7% in the 3M vs. 74.8% in the 6M (HR = 0.99; 95%CI 0.69–1.45 p = 0.994).94.2% and 78.0% of pts completed 3 and 6 months of CT, respectively. Overall, 96.9% and 89.5% of patients completed 3 months (arm A) and 6 months (arm B) of CT, respectively. Median oxaliplatin doses intensity were 97.3% in 3M and 73.2% in 6M (505.0 and 738.3 mg/m2).Overall maximum neuropathy during treatment grade 2/3-4 was 23.9/5.9%in 3M and38.7/13.7%in 6M; p &lt; 0.0001. In addition, worst grade 2/3-4 diarrhea was 11.1/4/0 in 3M and in 12.3/7.36M; p = 0.03. Conclusions: Since the HORG-IDEA study was designed in order to contribute patients in the IDEA project, the result on the study should be interpreted together with those of the whole IDEA project. Nevertheless, the results of the HORG-IDEA study are in line with those of the whole IDEA project, indicating that the results are depended on the administered adjuvant regimen, and the choice of regimen and duration should be depended on tumor characteristics and patient preference. Clinical trial information: NCT01308086.
Update on Systemic Prostate Cancer Therapies: Management of Metastatic Castration-resistant Prostate Cancer in the Era of Precision Oncology
Authors: Philipp Nuhn, Johann S. De Bono, Karim Fizazi, Stephen J. Freedland, Maurizio Grilli, Philip W. Kantoff, Guru Sonpavde, Cora N. Sternberg, Srinivasan Yegnasubramanian, Emmanuel S. Antonarakis
Journal: European Urology (2018)
Long-term follow-up of patients with chronic HCV infection and compensated or decompensated cirrhosis following treatment with sofosbuvir-based regimens
Authors: A. Mangia, E. Lawitz, E. Gane, B. Conway, P. Ruane, A. Abergel, B. Mcnabb, A. Osinusi, F. Chen, H. Dvory-Sobol, D. Brainard, M. Subramanian, B. Leggett, José L.C. Panero, K. Agarwal, Z.H. Younes, A. Muir
Journal: Journal of Hepatology (2018)
Outcome after the use of SX-ELLA Danis bleeding stents for refractory variceal bleeding- a Vienna Multicenter Experience
Authors: N. Pfisterer, W. Dolak, T. Pachofszky, M. Schoniger-Hekele, B. Schuster, B. Tribl, M. Mandorfer, L. Unger, F. Riedl, P. Schwabl, T. Bucsics, K. König, L. Kramer, M. Gschwantler, C. Madl, M. Trauner, T. Reiberger
Journal: Journal of Hepatology (2018)
Hormone Replacement Therapy After Oophorectomy and Breast Cancer Risk Among <i>BRCA1</i> Mutation Carriers
Authors: Joanne Kotsopoulos, Jacek Gronwald, Beth Y. Karlan, Tomasz Huzarski, Nadine Tung, Pal Moller, Susan Armel, Henry T. Lynch, Leigha Senter, Andrea Eisen, Christian F. Singer, William D. Foulkes, Michelle R. Jacobson, Ping Sun, Jan Lubinski, Steven A. Narod
Journal: JAMA Oncology (2018)

Prophylactic bilateral salpingo-oophorectomy is recommended for BRCA1 mutation carriers to prevent ovarian cancer. Whether or not hormone replacement therapy (HRT) initiated after oophorectomy is associated with an increased risk of breast cancer has not been evaluated in a prospective study.To determine the association between HRT use and BRCA1-associated breast cancer.A prospective, longitudinal cohort study of BRCA1 and BRCA2 mutation carriers from 80 participating centers in 17 countries was conducted between 1995 and 2017 with a mean follow-up of 7.6 years. Participants had sought genetic testing for a BRCA1 or BRCA2 mutation because of a personal or family history of breast and/or ovarian cancer. Carriers of BRCA1 mutation with no personal medical history of cancer who underwent bilateral oophorectomy following enrollment were eligible for the cohort study.A follow-up questionnaire was administered every 2 years to obtain detailed information on HRT use. A left-truncated Cox proportional hazard analysis was used to estimate the hazard ratios (HRs) and 95% CIs associated with the initiation of HRT use postoophorectomy.Incident breast cancer.A total of 872 BRCA1 mutation carriers with a mean postoophorectomy follow-up period of 7.6 years (range, 0.4-22.1) were included in this study. Mean (SD) age of participants was 43.4 (8.5) years. Among these, 92 (10.6%) incident breast cancers were diagnosed. Overall, HRT use after oophorectomy was not associated with an increased risk of breast cancer. The HR was 0.97 (95% CI, 0.62-1.52; P = .89) for ever use of any type of HRT vs no use; however, the effects of estrogen alone and combination hormonal therapy were different. After 10 years of follow-up, the cumulative incidence of breast cancer among women who used estrogen-alone HRT was 12% compared with 22% among women who used estrogen plus progesterone HRT (absolute difference, 10%; log rank P = .04).These findings suggest that use of estrogen after oophorectomy does not increase the risk of breast cancer among women with a BRCA1 mutation and should reassure BRCA1 mutation carriers considering preventive surgery that HRT is safe. The possible adverse effect of progesterone-containing HRT warrants further study.
Allocating healthcare resources—seriously ill people should have priority
Authors: Malcolm Segall
Journal: BMJ (2018)

MPs characterise NICE’s appraisal system as not fit for purpose following its non-approval of cystic fibrosis medication Orkambi on cost effectiveness grounds.1 What underlies this criticism?

NICE’s approach is utilitarian. It aims to allocate healthcare resources across the population so as to maximise aggregate health gain (allocative efficiency).2 It applies a standard criterion for cost effectiveness of interventions and thus distributes resources to …
Detection and Automation Technologies for the Mass Production of Droplet Biomicrofluidics
Authors: Zongjie Wang
Journal: IEEE Reviews in Biomedical Engineering (2018)

Droplet microfluidics utilizes two immiscible flows to generate small droplets with the diameter of a few to a few hundred micrometers. These droplets are promising tools for biomedical engineering because of the high throughput and the ease to finely tune the microenvironments. In addition to the great success of droplet biomicrofluidics in the proof-of-concept biosensing, regenerative medicine, and drug delivery, few droplet biomicrofluidic devices have a transformative impact on the industrial and clinical applications. The main issues are the low volume throughput and the lack of proper methods for quality control and automation. This review covers the methodologies for the mass production, detection, and automation of droplet generators. Recent advances in droplet mass production using parallelized devices and modified junction structures are discussed. Detection techniques, including optical and electrical detection methods, are comprehensively reviewed in detail. Newly emerged droplet closed-loop control systems are surveyed to highlight the progress in system integration and automation. Overall, with the advances in parallel droplet generation, highly sensitive detection, and robust closed-loop regulation, it is anticipated that the productivity and reliability of droplet biomicrofluidics will be significantly improved to meet the industrial and clinical needs.
Effect of metabolic syndrome on cardiovascular, hepatic events, and death in chronic hepatitis B patients: Methodological issues
Authors: Erfan Ayubi, Saeid Safiri, Mohadeseh Sani, Amin Doosti‐Irani, Ali Sanjari Moghaddam
Journal: Hepatology (2016)

Potential conflict of interest: Nothing to report. TO THE EDITOR: We were interested to read the article by Cheng et al. published in Hepatology in September 2016.1 The researchers aimed to evaluate the effect of various metabolic factors on the risks of hepatic events, cardiovascular events, and death in chronic hepatitis B patients. The results have demonstrated that metabolic syndrome (MetS) increased the risk of cardiovascular events, but not hepatic events and death.1 The researchers did not assess the bivariate correlation among the explanatory variables. It seems that the results of the study are biased by multicollinearity among MetS components. Actually, studies suggest that systolic blood pressure (SBP), diastolic blood pressure, and lipid profiles are highly correlated.2 The researchers assessed the effect of baseline MetS components and baseline liver stiffness measurement on the studied outcomes, but they only assumed a linear association between the exposures and the outcomes. Many studies found that there is a dose‐response or nonlinear association between each component of MetS with cardiovascular disease (CVD) events and death.3 For example, some studies found U‐shape or J‐shape associations between MetS components and CVD events.3 Full‐range associations between each MetS components and outcomes risk can be studied using advanced methods such as Restricted Cubic Splines in Cox models. Moreover, it seems that the estimated associations between MetS components and the studied outcomes are diluted. For example, it was found that SBP and adiposity ratios are subject to within‐person variability, and using a single measurement, such as baseline measurements, in the analysis is a source of bias.5 This bias is introduced as a regression dilution bias. Etiological associations between MetS components and CVD events and death should be appropriately checked using linear and nonlinear functions. Regression models with baseline measurements may be subject to regression dilution bias.
Before the beginning: nutrition and lifestyle in the preconception period and its importance for future health
Authors: Judith Stephenson, Nicola Heslehurst, Jennifer Hall, Danielle A J M Schoenaker, Jayne Hutchinson, Janet E Cade, Lucilla Poston, Geraldine Barrett, Sarah R Crozier, Mary Barker, Kalyanaraman Kumaran, Chittaranjan S Yajnik, Janis Baird, Gita D Mishra
Journal: The Lancet (2018)
Effects of Talaromyces marneffei infection on mortality of HIV/AIDS patients in southern China: a retrospective cohort study
Authors: J. Jiang, S. Meng, S. Huang, Y. Ruan, X. Lu, J.Z. Li, N. Wu, J. Huang, Z. Xie, B. Liang, J. Deng, B. Zhou, X. Chen, C. Ning, Y. Liao, W. Wei, J. Lai, L. Ye, F. Wu, H. Liang
Journal: Clinical Microbiology and Infection (2018)
Usefulness of serum metabolic profiling in the search of novel diagnostic biomarkers for primary sclerosing cholangitis, intrahepatic cholangiocarcinoma and hepatocellular carcinoma
Authors: Jesús Banales, M. Iñarrairaegui, A. Arbelaiz, P. Milkiewicz, J. Muntané, A. Lacasta, L. Muñoz-Bellvis, L.M. Gonzalez, E. Arretxe, C. Alonso, L. Bujanda, J. Marin, B. Sangro, R. Macias
Journal: Journal of Hepatology (2018)
Reply to the Reply to Andrew J. Portis and Matthew F. Bultitude's Letter to the Editor re: Zhangqun Ye, Guohua Zeng, Huan Yang, et al. Efficacy and Safety of Tamsulosin in Medical Expulsive Therapy for Distal Ureteral Stones with Renal Colic: A Multicenter, Randomized, Double-blind, Placebo-controlled Trial. Eur Urol 2018;73:385–91
Authors: Andrew J. Portis, Matthew F. Bultitude
Journal: European Urology (2018)
Glutaminase 1 targeting in non-alcoholic steatohepatitis
Authors: J. Simón, M. Nunez, P.F. Tussy, L. Barbier-Torres, D.F. Ramos, B.G. Santos, F.L. Otsoa, V.G. de Juan, C. Alonso, P. Iruzubieta, S.M.V. Liempd, A. Castro, M. Varela-Rey, J. Falcon-Perez, E. Villa, J. Crespo, S.C. Lu, J. Matos, P. Aspichueta, T.C. Delgado, M.L. Martínez-Chantar
Journal: Journal of Hepatology (2018)
The faecal microbiome of patients with autoimmune hepatitis is characterised by reduced diversity and is different from healthy subjects and patients with ulcerative colitis
Authors: T. Liwinski, C. Casar, M.-C. Rühlemann, C. Bang, F.-A. Heinsen, R. Zenouzi, D. Gerald, W. Lieb, A. Lohse, A. Franke, C. Schramm
Journal: Journal of Hepatology (2018)
Abstract 11330: E/e’ is a Powerful Predictor of Survival After a First-Ever Non-ST Elevation Myocardial Infarction
Authors: Andrew Lin, Christopher Kwan, Joanne Sippel, Kristyan Guppy-Coles, Christopher Hammett, Liza Thomas, John J Atherton, Sandhir B Prasad
Journal: Circulation (2016)

Introduction: Significant LV diastolic dysfunction is associated with a poorer prognosis following acute MI. The ratio of early mitral inflow velocity to mitral annular early diastolic velocity (E/e’) is a strong non-invasive correlate of LV filling pressures. Septal E/e’ &gt;15 has been well-validated as a predictor of survival in patients with STEMI, with limited data for patients with NSTEMI. Aim: To assess the prognostic significance of E/e’ measured early after a first-ever NSTEMI. We hypothesised that a septal E/e’ &gt;15 would predict poorer survival following NSTEMI. Methods: Data analysis on 332 consecutive patients who underwent coronary angiography for a first-ever NSTEMI at a single large tertiary referral centre from January 2013 to December 2014. Transthoracic echocardiography was performed within 24 hours of admission. Outcomes data were obtained from a statewide registry, with the primary endpoint being all-cause mortality. Results: At a median follow-up time of 36 months, death occurred in 41 (12%) patients. Septal E/e’ was &gt;15 in 66 patients (20%) and was associated with excess mortality (log-rank statistic 17.7, P&lt;0.0001) (Figure 1). On univariate Cox regression analysis, E/e’ &gt;15, age &gt;80 years, diabetes, chronic kidney disease, LVEF, left atrial volume index &gt;34ml/m 2 and tricuspid regurgitation peak velocity &gt;2.8m/s were associated with the primary endpoint. On multivariate analysis, E/e’ &gt;15 was an independent predictor of all-cause mortality (HR 2.30, 95%CI 1.24-4.33, p=0.028), as was chronic kidney disease (HR 2.73, 95%CI 1.32-5.66, p=0.007) and LVEF (HR 0.96, 95%CI 0.93-0.98, p=0.001). Furthermore, E/e’ &gt;15 showed incremental prognostic value when added to LVEF. Conclusion: E/e’ is a powerful, independent predictor of survival following a first-ever NSTEMI. It is superior, in this setting, to most clinical variables and other echocardiographic parameters of diastolic dysfunction, and has additive prognostic value over LVEF.
ABC-08: A phase Ib, multi-centre, open-label study of a first-in-class nucleotide analogue NUC-1031 in combination with cisplatin in patients with locally advanced/metastatic biliary tract cancers.
Authors: Mairead Geraldine McNamara, John A. Bridgewater, Daniel H. Palmer, Harpreet Singh Wasan, David Ryder, Chathunissa Gnanaranjan, Essam Ahmed Ghazaly, T.R. Jeffry Evans, Juan W. Valle
Journal: Journal of Clinical Oncology (2018)

TPS544 Background: The UK ABC-02 study established cisplatin and gemcitabine as the reference regimen for first-line treatment of patients (pts) with advanced biliary tract cancers (BTCs) (median overall survival (OS): 11.7 months). No clinical studies since ABC-02 have reported an extension in OS, and therefore effective new agents/combinations are required. NUC-1031 was designed to improve on gemcitabine’s relatively poor efficacy by overcoming its associated key cancer resistance mechanisms, through cellular uptake independent of nucleoside transporters, activation independent of deoxycytidine kinase and protection from cytidine deaminase inactivation, resulting in over 200x the intracellular levels of the anti-cancer metabolite, dFdCTP, greater stability and reduction in the generation of toxic metabolites. NUC-1031 showed activity as monotherapy in a phase I/II study in 7 pts with BTC, refractory to all standard treatments (Blagden et al ASCO 2015; abstract 2514). Methods: ABC-08 is a multi-centre phase Ib study of NUC-1031 combined with cisplatin in pts with non-resectable or recurrent/metastatic cholangiocarcinoma, gallbladder or ampullary carcinoma, aged ≥18 years with an ECOG performance status of 0-1, who have received no prior systemic therapy. The starting dose for NUC-1031 is 625 mg/m 2 administered IV on days 1 and 8 in combination with cisplatin (standard dose of 25 mg/m 2 ) (21 day schedule). The dose will be escalated sequentially in cohorts of 3-6 pts using an accelerated titration procedure (725mg/m 2 , 825mg/m 2 , 925mg/m 2 ). Treatment will continue until intolerable toxicity/progressive disease. The primary endpoints are safety and RP2D. Secondary endpoints are progression-free survival, OS, response rate and pharmacokinetic endpoints, including assessments of multiple plasma and intracellular analytes: NUC-1031, cisplatin, dFdC, dFdCMP, dFdCDP, dFdCTP and dFdU, and will be correlated with safety profile and clinical activity. Planned accrual is 15-24 pts over 2 years. Cohort 1 has been completed without dose-limiting toxicities. Enrolment to cohort 2 is on-going. Clinical trial information: NCT02351765.
Prognostic value of progranulin in patients with colorectal cancer underwent curative resection.
Authors: Dong-Hoe Koo, In-Gu Do, Sukjoong Oh, Kyungeun Kim, Jin Hee Sohn, Soo-Kyung Park, Hyo-Joon Yang, Yoon Suk Jung, Park Dong Il, Kyung Uk Jung, Hyung Ook Kim, Hungdai Kim, Ginette Serrero, Ho-Kyung Chun
Journal: Journal of Clinical Oncology (2018)

696 Background: Progranulin (PGRN), characterized as an autocrine growth and survival factor, is known to stimulate the tumorigenesis and proliferation of several cancer cell types. Evidence has emerged for a potential role of PGRN as biomarkers in some diseases, however, little is known about the prognostic role of PGRN in colorectal cancers (CRCs). Methods: A retrospective analysis was performed on patients with CRCs underwent curative resection between May 2013 and June 2015. PGRN expression in tumor cells was semiquantitatively categorized (no expression, 0; weak/focal, 1+; moderate/focal or diffuse, 2+; strong/diffuse, 3+). PGRN was considered positive when either tumor cells were shown with 2+ or 3+ staining intensity. Results: A total of 109 patients (28 stage I, 32 stage II, and 49 stage III) were analyzed. The median age was 67 years (range, 30–86) and 66 patients (61%) were male. Thirty-eight patients (35%) had high tumor PGRN expression (PGRN-positive), and there was a trend of elevated pre-operative CEA and CA19–9 in patients with PGRN–positive tumor compared to those with PGRN–negative tumor (CEA, 49% vs. 21%, P = 0.003; CA19–9, 21% vs. 7%; P = 0.077). The median follow-up duration for surviving patients was 28.9 months (interquartile range, 22.5–33.9). The 3–year RFS and OS were 83.7% (95% CI, 76.8–90.6) and 96.0% (95% CI, 92.3–99.7), respectively. Patients with PGRN–positive tumors had a worse recurrence free survival (RFS) with a 66.8% at 3–year (95% CI, 51.8–81.8) compared to PGRN–negative patients with a 92.4% at 3–year (95% CI, 86.2–98.6; P = 0.01). Multivariate analysis for RFS showed that PGRN–positive tumors (hazard ratio [HR] 4.61, 95% CI, 1.26–16.93; P = 0.021) and age ( &gt; 66 years, HR 8.87, 95% CI, 1.94–40.53; P = 0.005), stage (III, HR 8.56, 95% CI, 2.02–36.27; P = 0.004) and perineural invasion (HR 4.64, 95% CI, 1.05–20.62; P = 0.043) were prognostic factors independently associated with poor RFS after adjusting for possible confounding factors including sex, MSI status, tumor location, KRAS status, and lympho-vascular invasion. Conclusions: PGRN overexpression was significantly associated with poor RFS in patients with CRCs underwent curative resection.
Multiple Liver Lesions in a Woman With Asthenia, Anorexia, and Fever
Authors: Li Xu, Haidong Tan, Zhiying Yang
Journal: JAMA Surgery (2018)

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