Spatially matched in vivo and ex vivo MR metabolic profiles of prostate cancer – investigation of a correlation with Gleason score

MR metabolic profiling of the prostate is promising as an additional diagnostic approach to separate indolent from aggressive prostate cancer. The objective of this study was to assess the relationship between the Gleason score and the metabolic biomarker (choline + creatine + spermine)/citrate (CCS/C) measured by ex vivo high‐resolution magic angle spinning MRS (HR‐MAS MRS) and in vivo MRSI, and to evaluate the correlation between in vivo‐ and ex vivo‐measured metabolite ratios from spatially matched prostate regions. Patients (n = 13) underwent in vivo MRSI prior to radical prostatectomy. A prostate tissue slice was snap‐frozen shortly after surgery and the locations of tissue samples (n = 40) collected for ex vivo HR‐MAS were matched to in vivo MRSI voxels (n = 40). In vivo MRSI was performed on a 3T clinical MR system and ex vivo HR‐MAS on a 14.1T magnet. Relative metabolite concentrations were calculated by LCModel fitting of in vivo spectra and by peak integration of ex vivo spectra. Spearman's rank correlations (ρ) between CCS/C from in vivo and ex vivo MR spectra, and with their corresponding Gleason score, were calculated. There was a strong positive correlation between the Gleason score and CCS/C measured both in vivo and ex vivo (ρ = 0.77 and ρ = 0.69, respectively; p < 0.001), and between in vivo and ex vivo metabolite ratios from spatially matched regions (ρ = 0.67, p < 0.001). Our data indicate that MR metabolic profiling is a potentially useful tool for the assessment of cancer aggressiveness. Moreover, the good correlation between in vivo‐ and ex vivo‐measured CCS/C demonstrates that our method is able to bridge MRSI and HR‐MAS molecular analysis. Copyright © 2012 John Wiley & Sons, Ltd.     

Serum proinflammatory cytokines and nutritional status in pediatric chronic liver disease

AIM: To evaluate the nutritional status and its association with proinflammatory cytokines in children with chronic liver disease.METHODS: We performed a cross-sectional study with 43 children and adolescents, aged 0 to 17 years, diagnosed with chronic liver disease. All patients regularly attended the Pediatric Hepatology Unit and were under nutritional follow up. The exclusion criteria were fever from any etiology at the time of enrollment, inborn errors of the metabolism and any chronic illness. The severity of liver disease was assessed by Child-Pugh, Model for End-stage Liver Disease(MELD) and Pediatric End Stage Liver Disease(PELD) scores. Anthropometric parameters were height/age, body mass index/age and triceps skinfold/age according to World Health Organization standards. The cutoff points for nutritional status were risk of malnutrition(Z-score -1.00) and malnutrition(Z-score -2.00). Interleukin-1β(IL-1β), IL-6 and tumor necrosis factor-α levels were assessed by commercial ELISA kits. For multivariate analysis, linear regression was applied to assess the association between cytokine levels, disease severity and nutritional status. RESULTS: The median(25th-75 th centile) age of the study population was 60(17-116)-mo-old, and 53.5% were female. Biliary atresia was the main cause of chronic liver disease(72%). With respect to Child-Pugh score, cirrhotic patients were distributed as follows: 57.1% Child-Pugh A, a mild presentation of the disease, 34.3% Child-Pugh B, a moderate stage of cirrhosis and 8.6% Child-Pugh C, were considered severe cases. PELD and MELD scores were only above the cutoff point in 5 cases. IL-6 values were increased in patients at nutritional risk(34.9%) compared with those who were well-nourished [7.12(0.58-34.23) pg/m L vs 1.63(0.53-3.43) pg/m L; P = 0.02], correlating inversely with triceps skinfold-for-age z-score(rs =-0.61; P 0.001). IL-6 levels were associated with liver disease severity assessed by Child-Pugh score(P = 0.001). This association remained significant after adjusting for nutritional status in a linear regression model. CONCLUSION: High IL-6 levels were found in children with chronic liver disease at nutritional risk. Inflammatory activity may be related to nutritional status deterioration in these patients.     

Long-Term Immune Recovery After Hematopoietic Stem Cell Transplantation for ADA Deficiency: a Single-Center Experience

Journal of Clinical Immunology - Unconditioned hematopoietic stem cell transplantation (HSCT) is the recommended treatment for patients with adenosine deaminase (ADA)-deficient severe combined...