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Background and aim: Hepatic decompensation is a severe on-treatment adverse event for chronic hepatitis C treated with paritaprevir/ritonavir/ombitasvir and dasabuvir (PrOD). Till now, few papers regarding on-treatment hepatic decompensation have been reported. The study aims to analyze the general feature and predictive factors of on-treatment hepatic decompensation in hepatitis C virus (HCV) genotype 1b-infected patients with advanced fibrosis and compensated cirrhosis who receive treatment with PrOD. Methods: A real-word cohort enrolled 189 HCV genotype 1b patients with advanced fibrosis and compensated cirrhosis treated with 12-week PrOD. Clinical and laboratory data were analyzed between patients with and without on-treatment hepatic decompensation. Results: The sustained virologic response rate at 12 weeks after treatment was 97.3% in HCV subtype 1b patients with advanced fibrosis and cirrhosis. On-treatment hyperbilirubinemia (total bilirubin >2 mg/dL) occurred in 27 (14.3%) patients, and the incidence of the increase of total and direct form bilirubin was significantly different during treatment between patients with Child-Turcotte-Pugh score 5 and score 6. Five (18.5%) hyperbilirubinemia patients progressed to hepatic decompensation. Older age (adjusted OR: 1.2, 95% CI: 1.0–1.4) and albumin ≤3.6 g/dL (adjusted OR: 10.4, 95% CI: 1.3–81.2) may be two predictors for on-treatment hepatic decompensation by multivariate analysis. Conclusions: PrOD is an effective direct-acting antiviral agent for antiviral therapy in HCV genotype 1b patients with advanced fibrosis and cirrhosis. Hyperbilirubinemia is possibly the early warning feature of on-treatment hepatic decompensation. This serious adverse event of on-treatment hepatic decompensation is not common. Older age and low baseline albumin level may be predictive factors. [ABSTRACT FROM AUTHOR]

Background: Our systematic review summarizes the evidence concerning the accuracy of serum diagnostic and prognostic tests for colorectal cancer (CRC). Methods: The databases MEDLINE and EMBASE were searched iteratively to identify the relevant literature for serum markers of CRC published from 1950 to August 2012. The articles that provided adequate information to meet the requirements of the meta-analysis of diagnostic and prognostic markers were included. A 2-by-2 table of each diagnostic marker and its hazard ratio (HR) and the confidence interval (CI) of each prognostic marker was directly or indirectly extracted from the included papers, and the pooled sensitivity and specificity of the diagnostic marker and the pooled HR and the CI of the prognostic marker were subsequently calculated using the extracted data. Results: In total, 104 papers related to the diagnostic markers and 49 papers related to the prognostic serum markers of CRC were collected, and only 19 of 92 diagnostic markers were investigated in more than two studies, whereas 21 out of 44 prognostic markers were included in two or more studies. All of the pooled sensitivities of the diagnostic markers with > = 3 repetitions were less than 50%, and the meta-analyses of the prognostic markers with more than 3 studies were performed, VEGF with highest (2.245, CI: 1.347–3.744) and MMP-7 with lowest (1.099, CI: 1.018–1.187)) pooled HRs are presented. Conclusions: The quality of studies addressing the diagnostic and prognostic accuracy of the tests was poor, and the results were highly heterogeneous. The poor characteristics indicate that these tests are of little value for clinical practice. [ABSTRACT FROM AUTHOR]

Target agents are peculiar oncological drugs which differ from the traditional therapies in their ability of recognizing specific molecules expressed by tumor cells and microenvironment. Thus, their toxicity is generally lower than that associated to chemotherapy, and they represent nowadays a new standard of care in a number of tumors. This paper deals with the relationship between economic costs and toxicity of target agents. At this aim, a cluster analysis-based exploration of the main features of a large collection of them is carried out, with a specific focus on the variables leading to the identification of their toxicity and related costs. The analysis of the toxicity is based on the Severe Adverse Events (SAE) and Discontinuation (D) rates of each target agent considering data published on PubMed from 1965 to 2016 in the phase II and III studies that have led to the approval of these drugs for cancer patients by US Food and Drug Administration. The construction of the dataset represents a key step of the research, and is grounded on the critical analysis of a wide set of clinical studies. In order to capture different evaluation strategies of the toxicity, clustering is performed according to three different criteria (including Voronoi tessellation). Our procedure allows us to identify 5 different groups of target agents pooled by similar SAE and D rates and, at the same time, 3 groups based on target agents’ costs for 1 month and for the median whole duration of therapy. Results highlight several specific regularities for toxicity and costs. This study present several limitations, being realized starting from clinical trials and not from individual patients’ data. However, a macroscopic perspective suggests that costs are rather heterogeneous, and they do not clearly follow the clustering based on SAE and D rates. [ABSTRACT FROM AUTHOR]

Background: Prognostic models in metastatic castrate resistant prostate cancer (mCRPC) may have clinical utility. Using data from PDS, we aimed to 1) validate a contemporary prognostic model (Templeton et al., 2014) 2) evaluate prognostic impact of concomitant medications and PSA decrease 3) evaluate factors associated with docetaxel toxicity. Methods: We accessed data on 2,449 mCRPC patients in PDS. The existing model was validated with a continuous risk score, time-dependent receiver operating characteristic (ROC) curves, and corresponding time-dependent Area under the Curve (tAUC). The prognostic effects of concomitant medications and PSA response were assessed by Cox proportional hazards models. One year tAUC was calculated for multivariable prognostic model optimized to our data. Conditional logistic regression models were used to assess associations with grade 3/4 adverse events (G3/4 AE) at baseline and after cycle 1 of treatment. Results: Despite limitations of the PDS data set, the existing model was validated; one year AUC, was 0.68 (95% CI 95% CI, .66 to .71) to 0.78 (95%CI, .74 to .81) depending on the subset of datasets used. A new model was constructed with an AUC of .74 (.72 to .77). Concomitant medications low molecular weight heparin and warfarin were associated with poorer survival, Metformin and Cox2 inhibitors were associated with better outcome. PSA response was associated with survival, the effect of which was greatest early in follow-up. Age was associated with baseline risk of G3/4 AE. The odds of experiencing G3/4 AE later on in treatment were significantly greater for subjects who experienced a G3/4 AE in their first cycle (OR 3.53, 95% CI 2.53–4.91, p < .0001). Conclusion: Despite heterogeneous data collection protocols, PDS provides access to large datasets for novel outcomes analysis. In this paper, we demonstrate its utility for validating existing models and novel model generation including the utility of concomitant medications in outcome analyses, as well as the effect of PSA response on survival and toxicity prediction. [ABSTRACT FROM AUTHOR]

In small animal imaging studies, when the locations of the micro-structures of interest are unknown a priori, there is a simultaneous need for full-body coverage and high resolution. In MRI, additional requirements to image contrast and acquisition time will often make it impossible to acquire such images directly. Recently, a resolution enhancing post-processing technique called super-resolution reconstruction (SRR) has been demonstrated to improve visualization and localization of micro-structures in small animal MRI by combining multiple low-resolution acquisitions. However, when the field-of-view is large relative to the desired voxel size, solving the SRR problem becomes very expensive, in terms of both memory requirements and computation time. In this paper we introduce a novel local approach to SRR that aims to overcome the computational problems and allow researchers to efficiently explore both global and local characteristics in whole-body small animal MRI. The method integrates state-of-the-art image processing techniques from the areas of articulated atlas-based segmentation, planar reformation, and SRR. A proof-of-concept is provided with two case studies involving CT, BLI, and MRI data of bone and kidney tumors in a mouse model. We show that local SRR-MRI is a computationally efficient complementary imaging modality for the precise characterization of tumor metastases, and that the method provides a feasible high-resolution alternative to conventional MRI. [ABSTRACT FROM AUTHOR]

Background and Objectives: Current studies give us inconsistent results regarding the association of neoplasms and zinc(II) serum and tissues concentrations. The results of to-date studies using meta-analysis are summarized in this paper. Methods: Web of Science (Science citation index expanded), PubMed (Medline), Embase and CENTRAL were searched. Articles were reviewed by two evaluators; quality was assessed by Newcastle-Ottawa scale; meta-analysis was performed including meta-regression and publication bias analysis. Results: Analysis was performed on 114 case control, cohort and cross-sectional studies of 22737 participants. Decreased serum zinc level was found in patients with lung (effect size = −1.04), head and neck (effect size = −1.43), breast (effect size = −0.93), liver (effect size = −2.29), stomach (effect size = −1.59), and prostate (effect size = −1.36) cancers; elevation was not proven in any tumor. More specific zinc patterns are evident at tissue level, showing increase in breast cancer tissue (effect size = 1.80) and decrease in prostatic (effect size = −3.90), liver (effect size = −8.26), lung (effect size = −3.12), and thyroid cancer (effect size = −2.84). The rest of the included tumors brought ambiguous results, both in serum and tissue zinc levels across the studies. The association between zinc level and stage or grade of tumor has not been revealed by meta-regression. Conclusion: This study provides evidence on cancer-specific tissue zinc level alteration. Although serum zinc decrease was associated with most tumors mentioned herein, further – prospective - studies are needed. [ABSTRACT FROM AUTHOR]

Grade information has been considered in Yuan et al. (2007) wherein they proposed a Quasi-CRM method to incorporate the grade toxicity information in phase I trials. A potential problem with the Quasi-CRM model is that the choice of skeleton may dramatically vary the performance of the CRM model, which results in similar consequences for the Quasi-CRM model. In this paper, we propose a new model by utilizing bayesian model selection approach – Robust Quasi-CRM model – to tackle the above-mentioned pitfall with the Quasi-CRM model. The Robust Quasi-CRM model literally inherits the BMA-CRM model proposed by Yin and Yuan (2009) to consider a parallel of skeletons for Quasi-CRM. The superior performance of Robust Quasi-CRM model was demonstrated by extensive simulation studies. We conclude that the proposed method can be freely used in real practice. [ABSTRACT FROM AUTHOR]

Background: Some authors have studied the relationship between the presence of polyps, adenomas and cancers of upper gastrointestinal tract (stomach and duodenum) and risk of colorectal polyps and neoplasms; however, the results are controversial, which may be due to study sample size, populations, design, clinical features, and so on. No meta-analysis, which can be generalized to a larger population and could provide a quantitative pooled risk estimate of the relationship, of this issue existed so far. Methods: We performed a meta-analysis to evaluate risk of colorectal polyps or neoplasms in patients with polyps, adenomas or cancers in upper gastrointestinal tract comparing with controls. A search was conducted through PubMed, EMBASE, reference lists of potentially relevant papers, and practice guidelines up to 27 November 2013 without languages restriction. Odd ratios (ORs) were pooled using random-effects models. Results: The search yielded 3 prospective and 21 retrospective case-control studies (n = 37152 participants). The principal findings included: (1) OR for colorectal polyps was 1.15 (95% CI, 1.04–1.26) in the gastric polyps group comparing with control groups; (2) Patients with gastric polyps and neoplasms have higher risk (OR, 1.31 [95% CI, 1.06–1.62], and 1.72 [95% CI, 1.42–2.09], respectively) of colorectal neoplasms comparing with their controls; and (3) Positive association was found between the presence of colorectal neoplasms and sporadic duodenal neoplasms (OR, 2.59; 95% CI, 1.64–4.11). Conclusions: Findings from present meta-analysis of 24 case-control studies suggest that the prevalence of colorectal polyps was higher in patients with gastric polyps than in those without gastric polyps, and the risk of colorectal neoplasms increases significantly in patients with gastric polyps, neoplasms, and duodenal neoplasms. Therefore, screening colonoscopy should be considered for patients with upper gastrointestinal polyps and neoplasms. [ABSTRACT FROM AUTHOR]