Improving acute kidney injury alerts in tertiary care by linking primary care data: An observational cohort using routine care data.

Objective: Acute kidney injury (AKI) is easily missed and underdiagnosed in routine clinical care. Timely AKI management is important to decrease morbidity and mortality risks. We recently implemented an AKI e-alert at the University Medical Center Utrecht, comparing plasma creatinine concentrations with historical creatinine baselines, thereby identifying patients with AKI.

Should we depend on reference intervals from manufacturer package inserts? Comparing TSH and FT4 reference intervals from four manufacturers with results from modern indirect methods and the direct method.

Objectives: Correct interpretation of thyroid function tests relies on correct reference intervals (RIs) for thyroid-stimulating hormone (TSH) and free thyroxine (FT4). ISO15189 mandates periodic verification of RIs, but laboratories struggle with cost-effective approaches. We investigated whether indirect methods (utilizing historical laboratory data) could replace the direct approach (utilizing healthy reference individuals) and compared results with manufacturer-provided RIs for TSH and FT4.

Folate reference interval estimation in the Dutch general population.

Background: Folate functions as an enzyme co-factor within the one-carbon metabolic pathway, providing key metabolites required for DNA synthesis and methylation. Hence, insufficient intake of folate can negatively affect health. As correct interpretation of folate status is dependent on a well-established reference interval, we set out to perform a new estimation following the restandardization of the Roche folate assay against the international folate standard.

Carbamylation of albumin is a cause for discrepancies between albumin assays.

Background: Several investigators have reported discrepancies between the bromocresol-purple (BCP), bromocresol-green (BCG) and immunonephelometric (INP) assays in dialysis patients. This study compared the abovementioned assays and investigated whether hemodialysis itself or carbamylation of albumin is the cause for this discrepancy.

Methods: Samples obtained from hemodialysis patients were analyzed by BCP, BCG and INP.

Multimodal liposomes for SPECT/MR imaging as a tool for in situ relaxivity measurements.

One of the major challenges of MR imaging is the quantification of local concentrations of contrast agents. Cellular uptake strongly influences different parameters such as the water exchange rate and the pool of water protons, and results in alteration of the contrast agent's relaxivity, therefore making it difficult to determine contrast agent concentrations based on the MR signal only. Here, we propose a multimodal radiolabeled paramagnetic liposomal contrast agent that allows simultaneous imaging with SPECT and MRI.

Dynamic changes in 1H-MR relaxometric properties of cell-internalized paramagnetic liposomes, as studied over a five-day period.

Molecular imaging based on MRI requires the use of amplification strategies in order to achieve sufficient sensitivity for the detection of low-level molecular markers. Recently, we described a combination of two amplification methods: (i) the use of paramagnetic liposomes that can be prepared with a high payload of Gd(3+)-containing lipid; and (ii) targeting to a cell-surface receptor that can undergo multiple rounds of nanoparticle delivery in the cell, followed by recycling to the cell membrane. Liposome uptake was monitored over a period of 24 h and was found to lead to massive delivery in subcellular compartments.

Quantitative (1)H MRI, (19)F MRI, and (19)F MRS of cell-internalized perfluorocarbon paramagnetic nanoparticles.

In vivo molecular imaging with targeted MRI contrast agents will require sensitive methods to quantify local concentrations of contrast agent, enabling not only imaging-based recognition of pathological biomarkers but also detection of changes in expression levels as a consequence of disease development, therapeutic interventions or recurrence of disease. In recent years, targeted paramagnetic perfluorocarbon emulsions have been frequently applied in this context, permitting high-resolution (1)H MRI combined with quantitative (19)F MR imaging or spectroscopy, under the assumption that the fluorine signal is not altered by the local tissue and cellular environment. In this in vitro study we have investigated the (19)F MR-based quantification potential of a paramagnetic perfluorocarbon emulsion conjugated with RGD-peptide to target the cell-internalizing α(ν)β(3)-integrin expressed on endothelial cells, using a combination of (1)H MRI, (19)F MRI and (19)F MRS.

Methods for an improved detection of the MRI-CEST effect.

CEST imaging is a recently introduced MRI contrast modality based on the use of endogenous or exogenous molecules whose exchangeable proton pools transfer saturated magnetization to bulk water, thus creating negative contrast. One of the critical issues for further development of these agents is represented by their limited sensitivity in vivo. The aim of this work is to improve the detection of CEST agents by exploring new approaches through which the saturation transfer (ST) effect can be enhanced.

Cellular compartmentalization of internalized paramagnetic liposomes strongly influences both T1 and T2 relaxivity.

In recent years, numerous Gd(3+)-based contrast agents have been developed to enable target-specific MR imaging of in vivo processes at the molecular level. The combination of powerful contrast agents and amplification strategies, aimed at increasing the contrast agent dose at the target site, is an often-used strategy to improve the sensitivity of biomarker detection. One such amplification mechanism is to target a disease-specific cell membrane receptor that can undergo multiple rounds of internalization following ligand binding and thus shuttle a sizeable amount of contrast agent into the target cell.

Three-compartment T1 relaxation model for intracellular paramagnetic contrast agents.

The goal of this work was to elaborate a model describing the effective longitudinal relaxation rate constant R(1) for (1)H(2)O in three cellular compartments experiencing possible equilibrium water exchange, and to apply this model to explain the effective R(1) dependence on the overall concentration of a cell-internalized Gd(3+)-based contrast agent (CA). The model voxel comprises three compartments representing extracellular, cytoplasmic, and vesicular (e.g.