Identification of IDH and TERTp mutations using dynamic susceptibility contrast MRI with deep learning in 162 gliomas.

PURPOSE: Isocitrate dehydrogenase (IDH) and telomerase reverse transcriptase gene promoter (TERTp) mutations play crucial roles in glioma biology. Such genetic information is typically obtained invasively from excised tumor tissue; however, these mutations need to be identified preoperatively for better treatment planning. The relative cerebral blood volume (rCBV) information derived from dynamic susceptibility contrast MRI (DSC-MRI) has been demonstrated to correlate with tumor vascularity, functionality, and biology, and might provide some information about the genetic alterations in gliomas before surgery. Therefore, this study aims to predict IDH and TERTp mutational subgroups in gliomas using deep learning applied to rCBV images. METHOD: After the generation of rCBV images from DSC-MRI data, classical machine learning algorithms were applied to the features obtained from the segmented tumor volumes to classify IDH and TERTp mutation subgroups. Furthermore, pre-trained convolutional neural networks (CNNs) and CNNs enhanced with attention gates were trained using rCBV images or a combination of rCBV and anatomical images to classify the mutational subgroups. RESULTS: The best accuracies obtained with classical machine learning algorithms were 83 %, 68 %, and 76 % for the identification of IDH mutational, TERTp mutational, and TERTp-only subgroups, respectively. On the other hand, the best-performing CNN model achieved 88 % accuracy (86 % sensitivity, 91 % specificity) for the IDH-mutational subgroups, 70 % accuracy (73 % sensitivity and 67 % specificity) for the TERTp-mutational subgroups, and 84 % accuracy (86 % sensitivity, 81 % specificity) for the TERTp-only subgroup using attention gates. CONCLUSIONS: DSC-MRI can be utilized to noninvasively classify IDH- and TERTp-based molecular subgroups of gliomas, facilitating preoperative identification of these genetic alterations.

Endocan and albuminuria in type 2 diabetes mellitus.

BACKGROUND: Endocan is a newly identified proteoglycan released from endothelium, stimulating angiogenesis and when increased, indicates endothelial activation (inflammation). Our aim was to examine the association between serum endocan levels and urine albumin-creatinine ratio (UACR). METHOD: One hundred and thirty-seven patients with type 2 diabetes mellitus and normal serum creatinine who had no co-morbidities other than hypertension, diabetic nephropathy, retinopathy, or neuropathy were divided into normoalbuminuria (G1), microalbuminuria (G2), and macroalbuminuria (G3) groups and compared cross-sectionally regarding serum endocan levels. RESULT: There were 55, 47, and 35 patients in G1, G2, and G3, respectively. The groups were comparable in terms of gender, age, duration of diabetes, diabetic neuropathy/retinopathy, fasting glucose, HbA1c, serum creatinine level, and eGFR. Patients in G3 had significantly higher blood pressure but lower serum albumin and endocan levels. UACR showed a negative bivariate correlation with serum endocan levels (r = -.282, p = .001). There was bivariate positive correlation between endocan and systolic blood pressure (r=.185, p = .030). In linear regression analysis, UACR was negatively correlated with endocan while positively correlated with systolic blood pressure, duration of diabetes, and platelet distribution width. CONCLUSION: Patients with macroalbuminuria had lower endocan levels, and increasing UACR was associated with decreasing serum endocan levels. Despite the occurrence of angiogenesis and glomerular hypertrophy in the early phase of diabetic nephropathy, ensuing significant renal injury over time may reduce the expression of endocan. Serum endocan levels may represent a novel marker for nephropathy progression.

GAS6 intron 8 c.834 + 7G > A gene polymorphism in diabetic nephropathy.

UNLABELLED: BACKGROUND - AIM: In animal experiments, growth arrest-specific 6 (Gas6) protein plays a key role in the development of mesangial cell and glomerular hypertrophy in the early phase of diabetic nephropathy, and diabetic nephropathy is prevented by warfarin-induced inhibition of GAS6 protein. It was shown that GAS6 intron 8 c.834 + 7G > A polymorphism is protective against type 2 diabetes mellitus, and AA genotype is associated with higher blood levels of GAS6 protein. Our aim is to investigate whether this polymorphism is a risk factor for diabetic nephropathy in type 2 diabetes mellitus. METHOD: Eighty-seven patients with diabetic nephropathy were compared with 66 non-diabetic controls in terms of GAS6 intron 8 c.834 + 7G > A polymorphism. Patients with history of stroke, ischemic heart disease were excluded. Each patient was examined by the ophthalmologist to determine diabetic retinopathy. RESULTS: Frequency of GG, GA and AA genotypes are similar in diabetic nephropathy and control groups according to GAS6 intron 8 c.834 + 7G > A polymorphism (p = .837). Rate of diabetic retinopathy was 54.02%. In the subgroup analysis, GA genotype was significantly more frequent than GG genotype in patients with diabetic retinopathy when compared to without diabetic retinopathy (p = .010). CONCLUSION: In our study, GAS6 intron 8 c.834 + 7G > A polymorphism was not associated with diabetic nephropathy in type 2 diabetes mellitus. However, heterozygous state of this polymorphism may be a risk factor for diabetic retinopathy in patients with diabetic nephropathy.