BACKGROUNDProliferative diabetic retinopathy (PDR) is one of the most important microvascular complications among the patients with diabetes. Intravitreal anti-vascular endothelial growth factor ...(anti-VEGF) agent enacts a key role in PDR. Some studies have dealt with the systemic exposure to these agents after intravitreal administration. However, renal dysfunction following this therapy has scarcely been reported. Hence, this study aimed to determine the effect of intravitreal bevacizumab treatment on the deterioration of renal function and proteinuria. MATERIALS AND METHODSThis present prospective observational study was performed on 40 patients with diabetic nephropathy and PDR and/or significant diabetic macular edema as the candidates for receiving intravitreal injection of bevacizumab. To evaluate renal function, changes in the urinary albumin-to-creatinine ratio (UACR), serum creatinine (SCr), and estimated glomerular filtration rate (eGFR) one month after injection were measured. Also, changes in systolic and diastolic blood pressures (BPs), plasma VEGF level, platelet, white blood cell (WBC) counts, and hemoglobin (Hb) level were measured at the baseline and one month after treatment. RESULTSThe mean age of the patients was 60.3 ± 9.2 years, and 33 patients were female. The decrease in the plasma VEGF level and platelet count, as well as the increase in diastolic BP, and Hb level were significant. However, systolic BP and WBC count remained unchanged. There were no significant changes in UACR, SCr, and eGFR after the injection as compared to baseline (P>0.05). CONCLUSIONOur study indicated that intravitreal bevacizumab injection was not associated with renal dysfunction and proteinuria in patients with diabetic nephropathy. Nevertheless, diastolic BP and Hb level could increase after one month.
Abstract
Understanding the immune microenvironment in pediatric low-grade glioma (pLGG) patients may help in identification of the patients who benefit from anti-tumor immunotherapies. However, ...surgical resection is not feasible for many pLGG tumors in certain anatomical locations. Therefore, developing non-invasive tools that characterize the tumor microenvironment prior to therapeutic interventions could contribute to stratification and enrollment of the patients into relevant clinical trials. In this work, we derived radiomic signatures of immune profiles (radioimmunomics) based on machine learning (ML) analysis of readily available conventional MRI scans. Transcriptomic data for a cohort of 197 subjects was retrospectively collected from Open Pediatric Brain Tumor Atlas (OpenPBTA). The patients were categorized into three groups (Group1-3) based on their immunological profiles using consensus clustering algorithm. This analysis revealed greater immune cell infiltration in non-BRAF mutated pLGGs. Group1 showed more enrichment in M1 macrophages, and microenvironment and immune scores compared to Group2 and Group3. Elevated tumor inflammation score (TIS), as a predictor of clinical response to anti-PD-1 blockade, was observed in Group1 compared to Group2 (p= 1.4e-7) and Group3 (p= 0.0054). Radiomic features, including volumetric, morphologic, histogram, and texture descriptors, were extracted from the segmented tumor regions on multiparametric MRI (mpMRI) scans of 71 (of 197) patients. Multivariate ML models were trained to predict the three immunological groups based on radiomic features using cross-validated random forest classifier along with recursive feature elimination, which yielded AUC of 0.72 for this multi-class classification problem. Our findings indicate the presence of distinct immunological groups in pLGG tumors, with possibly more favorable response to immunotherapies in Group1 tumors. Furthermore, we developed radioimmunomic signatures based on pre-operative conventional mpMRI that can potentially stratify the patients based on their immune tumor microenvironment. Based on these initial promising results, we are exploring additional features to increase the accuracy of radioimmunomics model.
Abstract
The current era of advanced computing has allowed for the development and implementation of the field of radiomics. In pediatric neuro-oncology, radiomics has been applied in determination ...of tumor histology, identification of disseminated disease, prognostication, and molecular classification of tumors (ie, radiogenomics). The field also comes with many challenges, such as limitations in study sample sizes, class imbalance, generalizability of the methods, and data harmonization across imaging centers. The aim of this review paper is twofold: first, to summarize existing literature in radiomics of pediatric neuro-oncology; second, to distill the themes and challenges of the field and discuss future directions in both a clinical and technical context.
Background: Proliferative diabetic retinopathy (PDR) is one of the most important microvascular complications among the patients with diabetes. Intravitreal anti-vascular endothelial growth factor ...(anti-VEGF) agent enacts a key role in PDR. Some studies have dealt with the systemic exposure to these agents after intravitreal administration. However, renal dysfunction following this therapy has scarcely been reported. Hence, this study aimed to determine the effect of intravitreal bevacizumab treatment on the deterioration of renal function and proteinuria.
Materials and Methods: This present prospective observational study was performed on 40 patients with diabetic nephropathy and PDR and/or significant diabetic macular edema as the candidates for receiving intravitreal injection of bevacizumab. To evaluate renal function, changes in the urinary albumin-to-creatinine ratio (UACR), serum creatinine (SCr), and estimated glomerular filtration rate (eGFR) one month after injection were measured. Also, changes in systolic and diastolic blood pressures (BPs), plasma VEGF level, platelet, white blood cell (WBC) counts, and hemoglobin (Hb) level were measured at the baseline and one month after treatment.
Results: The mean age of the patients was 60.3 ± 9.2 years, and 33 patients were female. The decrease in the plasma VEGF level and platelet count, as well as the increase in diastolic BP, and Hb level were significant. However, systolic BP and WBC count remained unchanged. There were no significant changes in UACR, SCr, and eGFR after the injection as compared to baseline (P>0.05).
Conclusion: Our study indicated that intravitreal bevacizumab injection was not associated with renal dysfunction and proteinuria in patients with diabetic nephropathy. Nevertheless, diastolic BP and Hb level could increase after one month. GMJ.2018;In press:e1299
Proliferative diabetic retinopathy (PDR) is one of the most important microvascular complications among the patients with diabetes. Intravitreal anti-vascular endothelial growth factor (anti-VEGF) ...agent enacts a key role in PDR. Some studies have dealt with the systemic exposure to these agents after intravitreal administration. However, renal dysfunction following this therapy has scarcely been reported. Hence, this study aimed to determine the effect of intravitreal bevacizumab treatment on the deterioration of renal function and proteinuria.
This present prospective observational study was performed on 40 patients with diabetic nephropathy and PDR and/or significant diabetic macular edema as the candidates for receiving intravitreal injection of bevacizumab. To evaluate renal function, changes in the urinary albumin-to-creatinine ratio (UACR), serum creatinine (SCr), and estimated glomerular filtration rate (eGFR) one month after injection were measured. Also, changes in systolic and diastolic blood pressures (BPs), plasma VEGF level, platelet, white blood cell (WBC) counts, and hemoglobin (Hb) level were measured at the baseline and one month after treatment.
The mean age of the patients was 60.3 ± 9.2 years, and 33 patients were female. The decrease in the plasma VEGF level and platelet count, as well as the increase in diastolic BP, and Hb level were significant. However, systolic BP and WBC count remained unchanged. There were no significant changes in UACR, SCr, and eGFR after the injection as compared to baseline (P>0.05).
Our study indicated that intravitreal bevacizumab injection was not associated with renal dysfunction and proteinuria in patients with diabetic nephropathy. Nevertheless, diastolic BP and Hb level could increase after one month.
Abstract
Background
Brain tumors are the most common solid tumors and the leading cause of cancer-related death among all childhood cancers. Tumor segmentation is essential in surgical and treatment ...planning, and response assessment and monitoring. However, manual segmentation is time-consuming and has high interoperator variability. We present a multi-institutional deep learning-based method for automated brain extraction and segmentation of pediatric brain tumors based on multi-parametric MRI scans.
Methods
Multi-parametric scans (T1w, T1w-CE, T2, and T2-FLAIR) of 244 pediatric patients (n = 215 internal and n = 29 external cohorts) with de novo brain tumors, including a variety of tumor subtypes, were preprocessed and manually segmented to identify the brain tissue and tumor subregions into four tumor subregions, i.e., enhancing tumor (ET), non-enhancing tumor (NET), cystic components (CC), and peritumoral edema (ED). The internal cohort was split into training (n = 151), validation (n = 43), and withheld internal test (n = 21) subsets. DeepMedic, a three-dimensional convolutional neural network, was trained and the model parameters were tuned. Finally, the network was evaluated on the withheld internal and external test cohorts.
Results
Dice similarity score (median ± SD) was 0.91 ± 0.10/0.88 ± 0.16 for the whole tumor, 0.73 ± 0.27/0.84 ± 0.29 for ET, 0.79 ± 19/0.74 ± 0.27 for union of all non-enhancing components (i.e., NET, CC, ED), and 0.98 ± 0.02 for brain tissue in both internal/external test sets.
Conclusions
Our proposed automated brain extraction and tumor subregion segmentation models demonstrated accurate performance on segmentation of the brain tissue and whole tumor regions in pediatric brain tumors and can facilitate detection of abnormal regions for further clinical measurements.
MR imaging is central to the assessment of tumor burden and changes over time in neuro-oncology. Several response assessment guidelines have been set forth by the Response Assessment in Pediatric ...Neuro-Oncology (RAPNO) working groups in different tumor histologies; however, the visual delineation of tumor components using MRIs is not always straightforward, and complexities not currently addressed by these criteria can introduce inter- and intra-observer variability in manual assessments. Differentiation of non-enhancing tumor from peritumoral edema, mild enhancement from absence of enhancement, and various cystic components can be challenging; particularly given a lack of sufficient and uniform imaging protocols in clinical practice. Automated tumor segmentation with artificial intelligence (AI) may be able to provide more objective delineations, but rely on accurate and consistent training data created manually (ground truth). Herein, this paper reviews existing challenges and potential solutions to identifying and defining subregions of pediatric brain tumors (PBTs) that are not explicitly addressed by current guidelines. The goal is to assert the importance of defining and adopting criteria for addressing these challenges, as it will be critical to achieving standardized tumor measurements and reproducible response assessment in PBTs, ultimately leading to more precise outcome metrics and accurate comparisons among clinical studies.
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