Unresectable Intrahepatic Cholangiocarcinoma: Multiparametric MR Imaging to Predict Patient Survival.

Purpose To determine the performance of magnetic resonance (MR) imaging-based tumor metrics for evaluation of response to transarterial chemoembolization (TACE) in patients with unresectable intrahepatic cholangiocarcinoma (ICCA). Materials and Methods Ninety-four patients with unresectable ICCA underwent baseline and follow-up MR imaging after TACE and were followed up until death or end of study duration. Lesions were analyzed for anatomic (Response Evaluation Criteria in Solid Tumors [RECIST] and tumor volume) and functional (viable tumor volume, viable tumor burden, and apparent diffusion coefficient [ADC]) volumetric MR parameters by using semiautomatic software. Response was assessed by using changes in viable tumor volume by using modified RECIST (mRECIST)-derived thresholds (three-dimensional mRECIST), viable tumor burden, and ADC. Overall survival was the primary endpoint. Cox-regression and Kaplan-Meier survival analysis were used. Results Tumor volume did not change after TACE (P = .07) whereas RECIST diameter showed a small change (-2.6%; P = .02). There was an increase in ADC (20.7%) and a decrease in viable tumor volume (-29.3%) and viable tumor burden (-29.1%; P < .001 for all). Higher overall survival was noted among responders by using thresholds of 25% increase in ADC, 66% decrease in viable tumor volume, and 50% decrease in viable tumor burden (log-rank test, P < .05). Hazard ratio for nonresponders by using ADC, three-dimensional mRECIST, and viable tumor burden at multivariable analysis was 2.9 (P = .004), 4.1 (P = .009), and 4.0 (P = .002), respectively. Survival differences were noted for patients who showed response by using all three parameters (ADC, three-dimensional mRECIST, and viable tumor burden) versus those who showed response by using either one or two of these parameters versus those who showed no response (P < .001). Conclusion Changes in volumetric ADC, viable tumor volume, and viable tumor burden at MR imaging provide prognostic information among patients with unresectable ICCA who undergo TACE. © RSNA, 2018 Online supplemental material is available for this article.

Prediction of post-TACE necrosis of hepatocellular carcinoma usingvolumetric enhancement on MRI and volumetric oil deposition on CT, with pathological correlation.

OBJECTIVE: To investigate whether volumetric enhancement on baseline MRI and volumetric oil deposition on unenhanced CT would predict HCC necrosis and response post-TACE. METHOD: Of 115 retrospective HCC patients (173 lesions) who underwent cTACE, a subset of 53 HCC patients underwent liver transplant (LT). Semiautomatic volumetric segmentation of target lesions was performed on dual imaging to assess the accuracy of predicting tumour necrosis after TACE in the whole cohort and at pathology in the LT group. Predicted percentage tumour necrosis is defined as 100 % - (%baseline MRI enhancement - %CT oil deposition). RESULTS: Mean predicted tumour necrosis by dual imaging modalities was 61.5 % ± 31.6%; mean percentage tumour necrosis on follow-up MRI was 63.8 % ± 31.5 %. In the LT group, mean predicted tumour necrosis by dual imaging modalities was 77.6 % ± 27.2 %; mean percentage necrosis at pathology was 78.7 % ± 31.5 %. There was a strong significant correlation between predicted tumour necrosis and volumetric necrosis on MRI follow-up (r = 0.889, p<0.001) and between predicted tumour necrosis and pathological necrosis (r = 0.871, p<0.001). CONCLUSION: Volumetric pre-TACE enhancement on MRI and post-TACE oil deposition in CT may accurately predict necrosis in treated HCC lesions. KEY POINTS: • Imaging-based tumour response can assist in therapeutic decisions. • Lipiodol retention as carrier agent in cTACE is a tumour necrosis biomarker. • Predicting tumour necrosis with dual imaging potentially obviates immediate post-treatment MRI. • Predicting tumour necrosis would facilitate further therapeutic decisions in HCC post-cTACE. • Pre-TACE MRI and post-TACE CT predict necrosis in treated HCC.

Association of interferon regulatory factor 5 (IRF5) gene polymorphisms with juvenile idiopathic arthritis.

Interferon regulatory factor 5 (IRF5) is a member of IRF family which induce signaling pathways and are involved in modulation of cell growth, differentiation, apoptosis, and immune system activity. Juvenile idiopathic arthritis (JIA) is an auto-inflammatory syndrome where the inflammatory markers are believed to play a fundamental role in its pathogenesis. In this study, we aimed to assess the association of IRF5 gene polymorphisms with susceptibility of JIA in Iranian population. Three IRF5 single-nucleotide polymorphisms (rs10954213 A/G, rs2004640 G/T, and rs3807306 G/T) were genotyped using TaqMan assays in 55 patients with JIA and 63 matched healthy individuals. The frequency of the IRF5 rs2004640 T allele was significantly higher (69 vs 45%, P value = 0.0013) in JIA group as compared to control. The frequency of the IRF5 rs 2004640 G allele was significantly higher in the control group in comparison to JIA group (54 vs 32%, P value = 0.001). Allele and genotype frequencies of the rs10954213 and rs3807306 did not show any significant difference between JIA and control group. IRF5 rs 2004640 T allele can be considered as a risk factor for the development of JIA and presence of rs 2004640 G may be act as protective factor.

Influence of MTHFR gene variations on perceived stress modification: Preliminary results of NURSE study.

Background: High level of perceived stress in nurses is due to a genetic predisposition and environmental stressors. The aim of NURSE (Nursing Unacquainted Related Stress Etiologies) study was to investigate the association of C677T MTHFR gene polymorphism and stress perception among nurses. Methods: In this comprehensive study, 216 female nurses were recruited. Perceived stress was assessed using the Cohen Perceived Stress Scale (PSS). Genomic DNA was extracted from peripheral blood, and MTHFR genotype was detected by the polymerase chain reaction. Results: MTHFR C677T genotype analysis revealed that half of the participants had normal C/C genotype, and the remaining half presented higher frequencies of C/T genotype (39.8%) compared to T/T genotype (10.2%). The mean±SD stress score in morning shift, night shift, and rotation was 15.39±4.75, 15.92±4.94, and 15.83±5.61, respectively (p= 0.7). Perceived stress score was more in highly educated group but it was not significant (p= 0.2). Distribution of different MTHFR genotypes in diverse groups revealed that in groups with more stress score, the frequency of heterozygote (C/T) and homozygote (T/T) genotypes increased. Data revealed that in low stress category, 87% of the participants had a normal genotype. However, in high stress category, 71.3% of the participants had a normal genotype. Conclusion: MTHFR genotype, independent of folate availability and probable confounding parameters, might be a potential risk factor of perceived stress among nurses.

Methylmalonic acidemia with emergency hypertension / Acidemia metilmalónica con hipertensión de emergencia

No disponible

IL4 gene polymorphisms in Iranian patients with autoimmune hepatitis.

BACKGROUND: Autoimmune hepatitis (AIH) is a chronic long-lasting hepatocellular inflammation associated with circulating auto antibodies. In addition to the genetic component, several cytokines have been implicated to be involved in AIH. This study was performed to investigate potential associations of AIH with IL4 gene variants. METHOD: The studied alleles and genotypes included: IL4G/T allele polymorphisms at position -1098 and C/T allele polymorphisms at two positions (-33 and -590) on the IL4 gene, in addition to the A/G allele polymorphisms at position +1902 on the IL4RA gene. RESULT: The IL4 C allele and CC genotype at position -590 and TT genotype at position -33 had a significantly higher frequency in AIH patients. CONCLUSION: This study identified the IL4 C allele and CC genotype susceptibility gene in AIH, which will provide better insights into the mechanisms of AIH and potential therapeutic interventions.

A Randomized Clinical Trial of Insulin Glargine and Aspart, Compared to NPH and Regular Insulin in Children with Type 1 Diabetes Mellitus.

OBJECTIVE: Appropriate treatment of patients with Type 1 diabetes mellitus (T1DM) is necessary to avoid further complications. This study was performed to compare the efficacy of insulin Glargine and Aspart with NPH insulin and regular insulin regimen in a group of children with T1DM. METHODS: Forty patients with T1DM were enrolled in this study. During run-in, all subjects were treated with conventional therapy consisting of twice-daily NPH and thrice-daily regular. Following randomization, 20 subjects received Glargine and Aspart and 20 subjects received NPH and Regular insulin. FINDINGS: Mean HbA1c was 8.8% and 8.6% at first and 8.4% and 8.2% at the end of study for subjects randomized initially to Glargine and Aspart and for those randomized to NPH and Regular, respectively (P>0.05). Mean fasting blood glucose (FBS) of the subjects randomized initially to Glargine and Aspart was 217±101 mg/dL, with no significant difference to 196±75 mg/dL for those randomized to NPH and Regular (P=0.48). This was also true at the end of the study. The difference in total cholesterol and triglyceride between the two groups in the beginning of study and at the end did not show any significance. CONCLUSION: The current study showed no significant difference in glycemic control [Glycated hemoglobin (HbA1c) and FBS] and lipid profile (total cholesterol and triglyceride) between two regimes.

Efficacy of combination therapy with erythropoietin and methylprednisolone in clinical recovery of severe relapse in multiple sclerosis.

Multiple sclerosis (MS) is a multifaceted disease in which genetic and environmental factors are involved. Although neurodegeneration aspect of MS has major influence in patients' disability, none of the available treatments have been shown to obviously reduce neurodegeneration. Recently, the role of Erythropoietin (EPO) as a neuroprotective and anti-inflammatory agent has been attracted tremendous interest. In the present randomized double-blind pilot study, we combined EPO with methylprednisolone (MPred) in severe motor relapsing-remitting MS (RR-MS) patients to target both inflammatory and neurodegenerative aspects of disease. Twenty patients with RR-MS in relapse phase were randomized into two groups. The case group (10 patients) received intravenous MPred (1,000 mg/24 h) and intravenous EPO (20,000 U/24 h) for five consecutive days, and the control group (10 patients) received just MPred at the same dose as the case group, and a placebo. Both groups were followed for 3 months by ambulatory index (AI), Expanded Disability Status Scale (EDSS) and by magnetic resonance imaging (MRI) parameters. Improvement in maximal distance walking, reflected by reduction in AI and EDSS, was observed in EPO group after second month and continued after 3 months. Furthermore, MRI data analysis showed significant reduction in the number of T2WI lesions in EPO group without any significant change in contrast enhancing and black hole lesions. There was no major side effect in EPO group. The results of this first therapeutic pilot trial in RR-MS patients are promising, but need to be validated in larger trials.

Interleukin-23 receptor single nucleotide polymorphisms in ulcerative colitis. A study in Iranian populations.

BACKGROUND/OBJECTIVE: Genetic factors seem to play an important role in the pathogenesis of ulcerative colitis (UC). Genome wide association studies showed a highly significant association between interleukin 23 receptor (IL23R) single nucleotide polymorphisms (SNPs) and Crohn's disease; however, there are contrary results regarding the disease-modifying effects of IL23R variants in UC. This study was performed in a group of patients with UC to test the possible role of IL23R SNPs in conferring susceptibility or protection against the disease. METHODS: The study was performed on 67 Iranian adult patients with UC and 78 healthy controls. Eight IL23R SNPs were genotyped, using real-time polymerase chain reaction (RT-PCR). The frequencies of alleles and genotype at each position were determined and compared between two groups of patients and controls. RESULTS: The frequency of the T allele at position rs1343151 was significantly higher in the patient group, compared to the controls (P=0.018). The TT genotype at the same position was also significantly overrepresented in the patient group (P=0.02). There was no significant difference in alleles and genotype frequencies of other SNPs between patients and controls. CONCLUSIONS: This study identified a new susceptibility locus associated with UC. Our findings provide further insight into the genetics of UC, which might be amenable to future therapeutic intervention.

Association of vitamin D receptor with longevity and healthy aging.

Longevity is a multifaceted trait in which variety of genes and environmental factors are involved. Newly, the role of vitamin D has been revived regarding its potential advantage on delaying the aging process. Vitamin D exerts its effect through vitamin D receptor (VDR). VDR-FokI is the only polymorphism which alters the VDR length. We examined the frequency of FokI genotypes in old age population as compared to young adults to determine the discerning genotype of FokI polymorphism leading to longer living. In addition, to highlight the position of FokІ polymorphism in quality of life; a cognitive function assessment was performed. 728 participants participated in this study of which 166 individuals were elderly residents of Kahrizak Charity Foundation. The rest were participants of Iranian Multicenter Osteoporosis Study (IMOS). Genomic DNA was extracted from peripheral blood and VDR genotype was detected by the polymerase chain reaction. The participants in the elderly group underwent a cognitive function assessment. Cognitive function was measured with the mini mental state examination (MMSE). Data were analyzed by SPSS 16.5. The prevalence of ff genotype showed 48% decrease in elderly population as compared to young adults (P=0.06). In addition, F allele was over-represented in the elderly group as compared to controls (P=0.05). Also, "FF" participants of elderly group had higher MMSE as compared to "ff" genotype (18.16Vs17.12). Our data suggest that single nucleotide polymorphisms (SNPs) in FokI may be possibly involved in longevity and cognitive function.