Biobanking for glomerular diseases: a study design and protocol for KOrea Renal biobank NEtwoRk System TOward NExt-generation analysis (KORNERSTONE)

Abstract Backgrounds Glomerular diseases, a set of debilitating and complex disease entities, are related to mortality and morbidity. To gain insight into pathophysiology and novel treatment targets of glomerular disease, various types of biospecimens linked to deep clinical phenotyping including clinical information, digital pathology, and well-defined outcomes are required. We provide the rationale and design of the KOrea Renal biobank NEtwoRk System TOward Next-generation analysis (KORNERSTONE). Methods The KORNERSTONE, which has been initiated by Korea Centres for Disease Control and Prevention, is designed as a multi-centre, prospective cohort study and biobank for glomerular diseases. Clinical data, questionnaires will be collected at the time of kidney biopsy and subsequently every 1 year after kidney biopsy. All of the clinical data will be extracted from the electrical health record and automatically uploaded to the web-based database. High-quality digital pathologies are obtained and connected in the database. Various types of biospecimens are collected at baseline and during follow-up: serum, urine, buffy coat, stool, glomerular complementary DNA (cDNA), tubulointerstitial cDNA. All data and biospecimens are processed and stored in a standardised manner. The primary outcomes are mortality and end-stage renal disease. The secondary outcomes will be deterioration renal function, remission of proteinuria, cardiovascular events and quality of life. Discussion Ethical approval has been obtained from the institutional review board of each participating centre and ethics oversight committee. The KORNERSTONE is designed to deliver pioneer insights into glomerular diseases. The study design allows comprehensive, integrated and high-quality data collection on baseline laboratory findings, clinical outcomes including administrative data and digital pathologic images. This may provide various biospecimens and information to many researchers, establish the rationale for future more individualised treatment strategies for glomerular diseases. Trial registration NCT03929887

Advanced Ultrasound Techniques for Neuroimaging in Pediatric Critical Care: A Review

Because of its portability, safety profile, and accessibility, ultrasound has been integral in pediatric neuroimaging. While conventional B-mode and Doppler ultrasound provide anatomic and limited flow information, new and developing advanced ultrasound techniques are facilitating real-time visualization of brain perfusion, microvascular flow, and changes in tissue stiffness in the brain. These techniques, which include contrast-enhanced ultrasound, microvascular imaging, and elastography, are providing new insights into and new methods of evaluating pathologies affecting children requiring critical care, including hypoxic–ischemic encephalopathy, stroke, and hydrocephalus. This review introduces advanced neurosonography techniques and their clinical applications in pediatric neurocritical care

Utility of Cerebral Microvascular Imaging in Infants Undergoing ECMO

Purpose: Infants who require extracorporeal membrane oxygenation (ECMO) therapy have an increased risk of neurological complications and mortality. Microvascular imaging (MVI) is an advanced Doppler technique that allows high-resolution visualization of microvasculature in the brain. We describe the feasibility and utility of MVI for the evaluation of cerebral microvascular perfusion in patients undergoing ECMO. Methods: We retrospectively analyzed brain MVI scans of neonates undergoing ECMO. Two pediatric radiologists qualitatively assessed MVI scans to determine the presence or absence of tortuosity, symmetry, heterogeneity, engorgement, and hypoperfusion of the basal ganglia–thalamus (BGT) region, as well as the presence or absence of white matter vascular engorgement and increased peri-gyral flow in the cortex. We tested the association between the presence of the aforementioned brain MVI features and clinical outcomes. Results: We included 30 patients, 14 of which were male (46.7%). The time of ECMO duration was 11.8 ± 6.9 days. The most prevalent microvascular finding in BGT was lenticulostriate vessel tortuosity (26/30, 86.7%), and the most common microvascular finding in the cortex was increased peri-gyral flow (10/24, 41.7%). Cortical white matter vascular engorgement was significantly associated with the presence of any poor outcome as defined by death, seizure, and/or cerebrovascular events on magnetic resonance imaging (p = 0.03). Conclusion: MVI is a feasible modality to evaluate cerebral perfusion in infants undergoing ECMO. Additionally, evidence of white matter vascular engorgement after ECMO cannulation could serve as a predictor of poor outcomes in this population

Single fluorescent chemosensor for multiple targets: sequential detection of Al3+ and pyrophosphate and selective detection of F- in near-perfect aqueous solution

A simple and easily fabricated chemosensor (1), based on 2-furoic hydrazide and diethylaminosalicylaldehyde moieties, was devised and synthesized. Sensor 1 showed selective changes in fluorescence behavior toward three analytes in near-perfect aqueous solution. Al3+ and F- recognized by fluorescence enhancement of 1 and their limits of detection (0.19 mu M for Al3+ and 1.9 mu M for F-) were markedly low compared to World Health Organization guidelines (7.4 mu M for Al3+ and 79 mu M for F-) for drinking water. Furthermore, sensor 1 was used to quantify Al3+ and F- in real water samples and image Al3+ in living cells. Interestingly, the resulting 1-Al3+ complex could be used to discriminate pyrophosphate (PPi) over competing anions, including phosphate-based anions, by decreased fluorescence. Sensing mechanisms of 1 toward Al3+, PPi, and F- were proposed based on photophysical studies and theoretical calculations

Evaluation of the Cerebrospinal Fluid Flow Dynamics with Microvascular Imaging Ultrasound in Infants

Purpose: Microvascular imaging ultrasound (MVI) can detect slow blood flow in small-caliber cerebral vessels. This technology may help assess flow in other intracranial structures, such as the ventricular system. In this study, we describe the use of MVI for characterizing intraventricular cerebrospinal fluid (CSF) flow dynamics in infants. Materials and methods: We included infants with brain ultrasound that had MVI B-Flow cine clips in the sagittal plane. Two blinded reviewers examined the images, dictated a diagnostic impression, and identified the third ventricle, cerebral aqueduct, fourth ventricle, and CSF flow direction. A third reviewer evaluated the discrepancies. We evaluated the association of visualization of CSF flow as detectable with MVI, with the diagnostic impressions. We also assessed the inter-rater reliability (IRR) for detecting CSF flow. Results: We evaluated 101 infants, mean age 40 ± 53 days. Based on brain MVI B-Flow, a total of 49 patients had normal brain US scans, 40 had hydrocephalus, 26 had intraventricular hemorrhage (IVH), and 14 had hydrocephalus+IVH. Using spatially moving MVI signal in the third ventricle, cerebral aqueduct, and fourth ventricle as the criteria for CSF flow, CSF flow was identified in 10.9% (n = 11), 15.8% (n = 16), and 16.8% (n = 17) of cases, respectively. Flow direction was detected in 19.8% (n = 20) of cases; 70% (n = 14) was caudocranial, 15% (n = 3) was craniocaudal, and 15% (n = 3) bidirectional, with IRR = 0.662, p < 0.001. Visualization of CSF flow was significantly associated with the presence of IVH alone (OR 9.7 [3.3–29.0], p < 0.001) and IVH+hydrocephalus (OR 12.4 [3.5–440], p < 0.001), but not with hydrocephalus alone (p = 0.116). Conclusion: This study demonstrates that MVI can detect CSF flow dynamics in infants with a history of post-hemorrhagic hydrocephalus with a high IRR

Effect of the Duration Time of a Nuclear Accident on Radiological Health Consequences

This study aimed to quantify the effect of duration time of a nuclear accident on the radiation dose of a densely populated area and the resulting acute health effects. In the case of nuclear accidents, the total emissions of radioactive materials can be classified into several categories. Therefore, the release information is very important for the assessment of risk to the public. We confirmed that when the duration time of the emissions are prolonged to 7 hours, the concentrations of radioactive substances in the ambient air are reduced by 50% compared to that when the duration time of emission is one hour. This means that the risk evaluation using only the first wind direction of an accident is very conservative, so it has to be used as a screening level for the risk assessment. Furthermore, it is judged that the proper control of the emission time of a nuclear accident can minimize the health effects on residents

Evaluation of the Cerebrospinal Fluid Flow Dynamics with Microvascular Imaging Ultrasound in Infants

Purpose: Microvascular imaging ultrasound (MVI) can detect slow blood flow in small-caliber cerebral vessels. This technology may help assess flow in other intracranial structures, such as the ventricular system. In this study, we describe the use of MVI for characterizing intraventricular cerebrospinal fluid (CSF) flow dynamics in infants. Materials and methods: We included infants with brain ultrasound that had MVI B-Flow cine clips in the sagittal plane. Two blinded reviewers examined the images, dictated a diagnostic impression, and identified the third ventricle, cerebral aqueduct, fourth ventricle, and CSF flow direction. A third reviewer evaluated the discrepancies. We evaluated the association of visualization of CSF flow as detectable with MVI, with the diagnostic impressions. We also assessed the inter-rater reliability (IRR) for detecting CSF flow. Results: We evaluated 101 infants, mean age 40 ± 53 days. Based on brain MVI B-Flow, a total of 49 patients had normal brain US scans, 40 had hydrocephalus, 26 had intraventricular hemorrhage (IVH), and 14 had hydrocephalus+IVH. Using spatially moving MVI signal in the third ventricle, cerebral aqueduct, and fourth ventricle as the criteria for CSF flow, CSF flow was identified in 10.9% (n = 11), 15.8% (n = 16), and 16.8% (n = 17) of cases, respectively. Flow direction was detected in 19.8% (n = 20) of cases; 70% (n = 14) was caudocranial, 15% (n = 3) was craniocaudal, and 15% (n = 3) bidirectional, with IRR = 0.662, p p p p = 0.116). Conclusion: This study demonstrates that MVI can detect CSF flow dynamics in infants with a history of post-hemorrhagic hydrocephalus with a high IRR