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Background. Quantification of extracellular volume (ECV) fraction by cardiovascular magnetic resonance (CMR) has emerged as a noninvasive diagnostic tool to assess myocardial fibrosis. Secreted frizzled-related protein 2 (SFRP2) appears to play an important role in cardiac fibrosis. We aimed to evaluate the association between SFRP2 and myocardial fibrosis and the prognostic value of ECV fraction in patients with heart failure (HF). Methods. In this prospective cohort study, 72 hospitalized adult patients (age≥18 years) with severe decompensated HF were included. CMR measurements and T1 mapping were performed to calculate ECV fraction. Serum SFRP2 level was detected by an enzyme-linked immunosorbent assay kit. All patients were followed up, and the primary outcomes were composite events including all-cause mortality and HF hospitalization. Results. During the median follow-up of 12 months, 27 (37.5%) patients experienced primary outcome events and had higher levels of N-terminal pro-B-type natriuretic peptide (NT-proBNP), SFRP2, and ECV fraction compared with those without events. In Pearson correlation analysis, levels of SFRP2 (r=0.33), high-sensitivity C-reactive protein (r=0.31), and hemoglobin A1c (r=0.29) were associated with ECV fraction (all P<0.05); however, in multivariate linear regression analysis, SFRP2 was the only significant factor determined for ECV fraction (rpartial=0.33, P=0.02). In multivariate Cox regression analysis, age (each 10 years, hazard ratio (HR) 1.13, 95% confidence interval (CI) 1.04–1.22), ECV fraction (per doubling, HR 1.68, 95% CI 1.03–2.74), and NT-proBNP (per doubling, HR 2.46, 95% CI 1.05–5.76) were independent risk factors for primary outcomes. Conclusions. Higher ECV fraction is associated with worsened prognosis in HF. SFRP2 is an independent biomarker for myocardial fibrosis. Further studies are needed to explore the potential therapeutic value of SFRP2 in myocardial fibrosis.

Background: The triglyceride–glucose (TyG) index had been proposed as a reliable surrogate marker of insulin resistance. We aimed to evaluate the association between TyG index and myocardial fibrosis, which was quantified by extracellular volume (ECV) fraction using cardiovascular magnetic resonance (CMR) examination, and their prognostic value in patients with heart failure (HF).Methods: In this retrospective cohort study, 103 hospitalized HF patients were included. ECV fraction was calculated using CMR measurements and T1 mapping. TyG index was calculated using fasting triglyceride and blood glucose. The primary outcome events were defined as all-cause mortality and HF hospitalization during follow-up.Results: During the median follow-up of 12.3 months, 39 patients (37.9%) experienced primary outcome events and had higher levels of TyG index, N-terminal pro–B-type natriuretic peptide (NT-proBNP), and ECV fraction compared with those without events. Multivariate linear regression analysis showed that the TyG index was the significant factor determined for ECV fraction (rpartial = 0.36, P = 0.01). In multivariate Cox regression analysis, presence of diabetes [hazard ratio (HR) = 1.28, 95% confidence interval (CI) = 1.01–1.62], higher TyG index (HR = 2.01, 95% CI = 1.03–4.01), ECV fraction (HR = 1.73, 95% CI = 1.04–2.88), and NT-proBNP (HR = 2.13, 95% CI = 1.08–4.20) were independent risk factors for the primary outcome events.Conclusions: TyG index is a novel biomarker of myocardial fibrosis in HF patients and can be considered as a useful risk stratification metric in the management of HF.

Purpose To assess the amide proton transfer-weighted (APTw) MRI features of isocitrate dehydrogenase (IDH)-wildtype and IDH-mutant grade II gliomas and to test the hypothesis that the APTw signal is a surrogate imaging marker for identifying IDH mutation status preoperatively. Methods Twenty-seven patients with pathologically confirmed low-grade glioma, who were previously scanned at 3T, were retrospectively analyzed. The Mann-Whitney test was used to evaluate relationships between APTw intensities for IDH-mutant and IDH-wildtype groups, and receiver operator characteristic (ROC) analysis was used to assess the diagnostic performance of APTw. Results Based on histopathology and molecular analysis, seven cases were diagnosed as IDH-wildtype grade II gliomas and 20 cases as IDH-mutant grade II gliomas. The maximum and minimum APTw values, based on multiple regions of interest, as well as the whole-tumor histogram-based mean and 50th percentile APTw values, were significantly higher in the IDH-wildtype gliomas than in the IDH-mutant groups. This corresponded to the areas under the ROC curves of 0.89, 0.76, 0.75, and 0.75, respectively, for the prediction of the IDH mutation status. Conclusion IDH-wildtype lesions typically were associated with relatively high APTw signal intensities as compared with IDH-mutant lesions. The APTw signal could be a valuable imaging biomarker by which to identify IDH1 mutation status in grade II gliomas. Magn Reson Med 78:1100–1109, 2017. © 2017 International Society for Magnetic Resonance in Medicine.

OBJECTIVES: To explore the feasibility of using amide proton transfer-weighted (APTw) MRI metrics as surrogate biomarkers to identify the O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status in glioblastoma (GBM). METHODS: Eighteen newly diagnosed GBM patients, who were previously scanned at 3T and had a confirmed MGMT methylation status, were retrospectively analyzed. For each case, a histogram analysis in the tumor mass was performed to evaluate several quantitative APTw MRI metrics. The Mann-Whitney test was used to evaluate the difference in APTw parameters between MGMT methylated and unmethylated GBMs, and the receiver-operator-characteristic analysis was further used to assess the diagnostic performance. RESULTS: Ten GBMs were found to harbor a methylated MGMT promoter, and eight GBMs were unmethylated. The Mean, Variance, 50(th) percentile, 90(th) percentile, and Width(10–90) APTw values were significantly higher in the MGMT unmethylated GBMs than in the MGMT methylated GBMs, with the areas under the receiver-operator-characteristic curves of 0.825, 0.837, 0.850, 0856, and 0.763, respectively, for the discrimination of MGMT promoter methylation status. CONCLUSIONS: APTw signal metrics have the potential to serve as valuable imaging biomarkers for identifying MGMT methylation status in the GBM population.

To determine the utility of amide proton transfer-weighted (APTw) MR imaging in distinguishing solitary brain metastases (SBMs) from glioblastomas (GBMs). Forty-five patients with SBMs and 43 patients with GBMs underwent conventional and APT-weighted sequences before clinical intervention. The APTw parameters and relative APTw (rAPTw) parameters in the tumour core and the peritumoral brain zone (PBZ) were obtained and compared between SBMs and GBMs. The receiver-operating characteristic (ROC) curve was used to assess the best parameter for distinguishing between the two groups. The APTwmax, APTwmin, APTwmean, rAPTwmax, rAPTwmin or rAPTwmean values in the tumour core were not significantly different between the SBM and GBM groups (P = 0.141, 0.361, 0.221, 0.305, 0.578 and 0.448, respectively). However, the APTwmax, APTwmin, APTwmean, rAPTwmax, rAPTwmin or rAPTwmean values in the PBZ were significantly lower in the SBM group than in the GBM group (P

Pancreatic cancer remains one of the most lethal malignancies, and insights into both personalized diagnosis and intervention of this disease are urgently needed. The rapid development of sequencing technologies has enabled the successive completion of a series of genetic and epigenetic sequencing studies of pancreatic cancer. The mutational landscape of pancreatic cancer is generally portrayed in terms of somatic mutations, structural variations, epigenetic alterations and the core signaling pathways. In recent years, four significant molecular subtype classifications of pancreatic cancer have been proposed based on the expression of transcription factors and downstream targets or the distribution of structural rearrangements. Increasing researches focus on the identification of somatic mutations and other genetic aberrations that drive pancreatic cancer has led to a new era of precision medicine based on molecular subtyping. However, few known molecular classifications are used to guide clinical strategies. Specific scientific, regulatory and ethical challenges must be overcome before genomic and transcriptomic discoveries can be translated into the clinic.

Previous studies that investigated the association between body mass index (BMI) and pancreatectomy outcomes have produced conflicting conclusions. We conducted this meta-analysis to assess the association between them.We searched PubMed, EMBASE, and Cochrane Library databases up to December 28, 2014. Patients were divided into high-BMI group (BMI ≥ 25 kg/m) and normal-BMI group (BMI25 kg/m). Postoperative and intraoperative outcomes were evaluated. Meta-regression and subgroup analysis were performed to evaluate any factors accountable for the heterogeneity. Meta-analysis was performed using a random-effect model.We included 22 studies involving 8994 patients. Patients in the high-BMI group had significantly increased postoperative pancreatic fistula rate (odds ratio [OR],1.96; 95% confidence interval [CI], 1.43-2.67), delayed gastric emptying rate (OR, 1.62; 95% CI, 1.15-2.29), wound infection rate (OR, 1.43; 95% CI, 1.07-1.93), operation time (mean difference [MD],15; 95% CI, 13.40-16.60), blood loss (MD, 270.71; 95% CI, 248.93-292.49), and length of hospital stay (MD, 2.87; 95% CI, 1.51-4.24). For modest heterogeneity in postoperative pancreatic fistula, regional distribution tended to be the contributor.High BMI not only increased the surgical difficulty but also decreased the surgical safety for pancreatectomy.

Pathogenesis of pancreatic ductal adenocarcinoma (PDAC) is thought to develop through the progression of precursor lesions, known as pancreatic intraepithelial neoplasias (PanIN). In the present study, we showed that c-Fos promoted proliferation, cell cycle and migration in pancreatic cancer cells. Caerulein was used to accelerate the pathogenesis of Pdx-cre; KrasG12D mice. During PanIN formation and development of PDAC, the expression of ERK and c-Fos increased concomitantly. When ERK activity was inhibited by U0126, the expression of c-Fos also decreased. Inactivation of ERK/c-Fos suppressed pancreatic lesions concurrently through proliferation, inflammation and apoptosis. Our findings suggest that the ERK/c-Fos pathway is required for PDAC initiation and progression.