Финансовое обеспечение деятельности туристического предприятия

Целью статьи является разработка рекомендаций по повышению эффективности финансового обеспечения деятельности туристического предприятия, определение приоритетных путей совершенствования финансовых показателей его деятельности

Albumin determined by bromocresol green leads to erroneous results in routine evaluation of patients with chronic kidney disease

Objectives: Measurement of plasma albumin is pivotal for clinical decision-making in patients with chronic kidney disease (CKD). Routinely used methods as bromocresol green (BCG) and bromocresol purple (BCP) can suffer from aselectivity, but the impact of aselectivity on the accuracy of plasma albumin results of CKD-patients is still unknown. Therefore, we evaluated the performance of BCG-, BCP- and JCTLM-endorsed immunological methods in patients with various stages of CKD. Methods:We evaluated the performance of commonly used albumin methods in patients with CKD stages G1 through G5, the latter divided in two groups based on whether they received hemodialysis treatment. In total, 163 patient plasma samples were measured at 14 laboratories, on six different BCG and BCP-platforms, and four different immunological platforms. The results were compared with an ERM-DA-470k-corrected nephelometric assay. The implications on outcome is evaluated by the proportion of patient results &lt;38g/L for the diagnosis of protein energy wasting. Results:Albumin results determined with BCP- and immunological methods showed the best agreement with the target value (92.7 and 86.2%, respectively vs. 66.7% for BCG, namely due to overestimation). The relative agreement of each method with the target value was platform-dependent, with larger variability in agreement between platforms noted for BCG and immunological methods (3.2-4.6 and 2.6-5.3%) as opposed to BCP (0.7-1.5%). The stage of CKD had similar effects on the variability in agreement for the three method-groups (0.6-1.8% vs. 0.7-1.5% vs. 0.4-1.6%). The differences between methods cause discrepancies in clinical decision-making, as structurally fewer patients were diagnosed with protein energy wasting upon using BCG-based albumin results. Conclusions: Our study shows that BCP is fit for the intended use to measure plasma albumin levels in CKD patients from all stages, including patients on hemodialysis. In contrast, most BCG-based platforms falsely overestimate the plasma albumin concentration.</p

Quantifying lymphocyte vacuolization serves as a measure of CLN3 disease severity

Background: The CLN3 disease spectrum ranges from a childhood-onset neurodegenerative disorder to a retina-only disease. Given the lack of metabolic disease severity markers, it may be difficult to provide adequate counseling, particularly when novel genetic variants are identified. In this study, we assessed whether lymphocyte vacuolization, a well-known yet poorly explored characteristic of CLN3 disease, could serve as a measure of disease severity. Methods: Peripheral blood obtained from healthy controls and CLN3 disease patients was used to assess lymphocyte vacuolization by (a) calculating the degree of vacuolization using light microscopy and (b) quantifying expression of lysosomal-associated membrane protein 1 (LAMP-1), using flow cytometry in lymphocyte subsets as well as a qualitative analysis using electron microscopy and ImageStream analysis. Results: Quantifying lymphocyte vacuolization allowed to differentiate between CLN3 disease phenotypes (P =.0001). On immunofluorescence, classical CLN3 disease lymphocytes exhibited abundant vacuole-shaped LAMP-1 expression, suggesting the use of LAMP-1 as a proxy for lymphocyte vacuolization. Using flow cytometry in lymphocyte subsets, quantifying intracellular LAMP-1 expression additionally allowed to differentiate between infection and storage and to differentiate between CLN3 phenotypes even more in-depth revealing that intracellular LAMP-1 expression was most pronounced in T-cells of classical-protracted CLN3 disease while it was most pronounced in B-cells of “retina-only” CLN3 disease. Conclusion: Lymphocyte vacuolization serves as a proxy for CLN3 disease severity. Quantifying vacuolization may help interpretation of novel genetic variants and provide an individualized readout for upcoming therapies

New mAb therapies in multiple myeloma : interference with blood transfusion compatibility testing

PURPOSE OF REVIEW: Immunotherapeutic strategies are emerging as novel therapeutic approaches in multiple myeloma, with several mAbs being in advanced stages of clinical development. Of these, CD38 targeting antibodies appear very promising. In trials with anti-CD38 mAb daratumumab, all patients demonstrated panreactivity in red blood cell (RBC) panel testing, complicating the selection of compatible RBCs for transfusion. This review provides an overview of the interferences and solutions to safely transfuse these patients. RECENT FINDINGS: CD38 is weakly expressed on human erythrocytes. Since the first reports on the interference, different solutions have been reported, including the neutralization of anti-CD38 mAbs in plasma by sCD38 or antiidiotype antibodies, CD38 depletion of RBCs using dithiothreitol or cord blood test cells, and transfusion of extensively typed RBCs. SUMMARY: All methods have (dis)advantages, and it depends on the facilities of the immunohematology laboratory what strategy to choose. As the selection of suitable RBC units can be seriously delayed, hospitals should have protocols to communicate this interference with patients, laboratories, and physicians in a timely manner. As CD38 antibodies may also have a role in the treatment of diseases beyond hematological malignancies, chances are high that health professionals will encounter this issue in the nearby future

New mAb therapies in multiple myeloma : interference with blood transfusion compatibility testing

PURPOSE OF REVIEW: Immunotherapeutic strategies are emerging as novel therapeutic approaches in multiple myeloma, with several mAbs being in advanced stages of clinical development. Of these, CD38 targeting antibodies appear very promising. In trials with anti-CD38 mAb daratumumab, all patients demonstrated panreactivity in red blood cell (RBC) panel testing, complicating the selection of compatible RBCs for transfusion. This review provides an overview of the interferences and solutions to safely transfuse these patients. RECENT FINDINGS: CD38 is weakly expressed on human erythrocytes. Since the first reports on the interference, different solutions have been reported, including the neutralization of anti-CD38 mAbs in plasma by sCD38 or antiidiotype antibodies, CD38 depletion of RBCs using dithiothreitol or cord blood test cells, and transfusion of extensively typed RBCs. SUMMARY: All methods have (dis)advantages, and it depends on the facilities of the immunohematology laboratory what strategy to choose. As the selection of suitable RBC units can be seriously delayed, hospitals should have protocols to communicate this interference with patients, laboratories, and physicians in a timely manner. As CD38 antibodies may also have a role in the treatment of diseases beyond hematological malignancies, chances are high that health professionals will encounter this issue in the nearby future

Pharmacokinetics of contrast agents targeted to the tumor vasculature in molecular magnetic resonance imaging

Molecular magnetic resonance imaging (MRI) is increasingly used to investigate tumor angiogenic activity non-invasively. However, the pharmacokinetic behavior and tumor penetration of the often large contrast agent particles is thus far unknown. Here, pharmacokinetic analysis of cyclic asparagine-glycine-arginine (cNGR) labeled paramagnetic quantum dots (pQDs) was developed to quantify the contrast agent's homing efficacy to activated endothelial cells of angiogenic tumor vessels using dynamic contrast-enhanced (DCE) MRI. cNGR homes to CD13, an overexpressed aminopeptidase on angiogenic tumor endothelial cells. First, a two-compartment pharmacokinetic model, comprising the blood space and endothelial cell surface, was compared with a three-compartment model additionally including the extravascular-extracellular component. The resulting extravasation parameter was irrelevantly small and was therefore neglected. Next, the association constant K-a, the dissociation constant k(d) and the fractional plasma volume v(p) were determined from the time-series data using the two-compartment model. Magnitude and spatial distribution of the parameters were compared for cNGR-labeled and unlabeled pQDs. The tumor area with significant K-a values was approximately twice as large for cNGR-pQDs compared with unlabeled pQDs (p &lt;0.05), indicating more contrast agent binding for cNGR-pQDs. Using cNGR-pQDs, a two-fold larger area with significant K-a was also found for the angiogenic tumor rim compared with tumor core (p &lt;0.05). It was furthermore found that both contrast agents perfused the tumor at all depths, thereby providing unequivocal evidence that rim/core differences can indeed be ascribed to stronger angiogenic activity in the rim. Summarizing, molecular DCE-MRI with pharmacokinetic modeling provides unique information on contrast agent delivery and angiogenic activity in tumors