Dialysis decision making in Canada, the United Kingdom, and the United States

This study was designed to determine the extent to which differences in criteria for dialysis patient selection and availability of financial resources cause the wide variation in acceptance rates for dialysis in Canada, the United Kingdom, and the United States. We also sought to determine whether there is agreement among nephrologists in the three countries on which patients should not be offered dialysis. We used a cross-sectional survey of all members of the Canadian Society of Nephrology and the Renal Association of Great Britain, and a randomized sample of 800 members of the American Society of Nephrology. Five case vignettes were presented asking for yes/no decisions on offering or not offering dialysis, together with ranking of factors considered important. We also inquired about dialysis resources and physician demographics. We compared responses by country. More nephrologists from the United Kingdom returned responses (83%) than Canadian (53%) or American (36%) nephrologists. American nephrologists offered dialysis more than Canadian or British nephrologists (three of five cases; P < 0.04 to P < 0.001) and ranked patient/family wishes (three of five cases; P < 0.057 to P < 0.0001) and fear of lawsuit (P < 0.04 to P = 0.0012) higher than British or Canadian nephrologists. Canadian and British nephrologists reported their perception of patients' quality of life as a reason to provide (P = 0.0019) or not provide (P = 0.068 to P = 0.0026) dialysis more often than their American counterparts. Despite these differences, nephrologists from each country did not differ by more than 30% on any decision and ranked factors almost identically. Ten percent and 12% of Canadian and British nephrologists, respectively, but only 2% of American nephrologists, reported refusing dialysis due to lack of resources (P < 0.0001). We conclude that the wide variation in dialysis acceptance rates in the three countries is somewhat influenced by differences in patient selection criteria and withholding of dialysis by nephrologists based on financial constraints, but that other factors, such as differences in rates of patient nonreferral for dialysis, contribute more significantly to the variation. Generally agreed on practice guidelines for dialysis patient selection appear possible.     

Magnetic resonance imaging of the lymph nodes: comparison with CT

This retrospective study of 144 patients was made to (a) assess the potential of magnetic resonance (MR) for demonstrating lymph nodes using spin-echo technique, (b) compare the MR results with those of CT, and (c) determine the optimal pulse-sequence interval (TR) and echo-delay time (TE) for imaging lymph nodes. The reported CT findings on normal lymph nodes were compared with MR findings in 60 patients who underwent MR imaging of the neck (20 patients), chest (20 patients), abdomen (10 patients), and pelvis (10 patients) for conditions other than lymph node disease. The results showed that CT is presently better than MR for imaging neck and abdominal lymph nodes less than 13 mm in diameter. The ability of MR to demonstrate normal-size (less than 10 mm) lymph nodes in the chest was comparable to that of CT. In addition, MR scans of 84 patients with proven abnormal lymph nodes (8 neck, 49 chest, and 27 abdomen and pelvis) were assessed: in 72 patients, these nodes had also been imaged by CT. MR and CT gave similar results with abnormal lymph nodes (greater than 13 or 15 mm), but MR displayed these nodes better because of its excellent soft-tissue contrast resolution. MR can clearly differentiate abnormal lymph nodes from normal fat, muscle, vessels, adult thymus, thyroid, and diaphragmatic crura, as well as from primary tumor and lymphoceles. Optimal demonstration of lymph nodes with MR required two sequences: one with a short TR and one with a long TR and long TE. Preliminary results indicate that MR holds great promise for the demonstration of lymph nodes in every part of the body.     

Metabolomic Pathways to Osteoporosis in Middle‐Aged Women: A Genome‐Metabolome‐Wide Mendelian Randomization Study

The metabolic state of the body can be a major determinant of bone health. We used a Mendelian randomization approach to identify metabolites causally associated with bone mass to better understand the biological mechanisms of osteoporosis. We tested bone phenotypes (femoral neck, total hip, and lumbar spine bone mineral density [BMD]) for association with 280 fasting blood metabolites in 6055 women from TwinsUK cohort with genomewide genotyping scans. Causal associations between metabolites and bone phenotypes were further assessed in a bidirectional Mendelian randomization study using genetic markers/scores as instrumental variables. Significant associations were replicated in 624 participants from the Hong Kong Osteoporosis Study (HKOS). Fifteen metabolites showed direct associations with bone phenotypes after adjusting for covariates and multiple testing. Using genetic instruments, four of these metabolites were found to be causally associated with hip or spine BMD. These included androsterone sulfate, epiandrosterone sulfate, 5alpha‐androstan‐3beta17beta‐diol disulfate (encoded by CYP3A5), and 4‐androsten‐3beta17beta‐diol disulfate (encoded by SULT2A1). In the HKOS population, all four metabolites showed significant associations with hip and spine BMD in the expected directions. No causal reverse association between BMD and any of the metabolites were found. In the first metabolome‐genomewide Mendelian randomization study of human bone mineral density, we identified four novel biomarkers causally associated with BMD. Our findings reveal novel biological pathways involved in the pathogenesis of osteoporosis. © 2017 American Society for Bone and Mineral Research.     

The relationship between the duration of platelet storage and the development of transfusion reactions

BACKGROUND: The incidence of platelet transfusion reactions may depend partly on the length of storage. The influence of reactions on the effectiveness of platelet transfusions is not known. STUDY DESIGN AND METHODS: Platelet transfusion reactions, identified by prospective monitoring, were analyzed for the effects of component type, recipient lymphocytotoxic antibodies, bacterial contamination, and duration of storage. Posttransfusion corrected count increments (CCIs) were used to evaluate the effectiveness of transfusions associated with reactions by comparing them to those of randomly selected transfusions without reactions. RESULTS: Reactions accompanied 4 percent of the 4926 transfusions given and included 119 febrile nonhemolytic transfusion reactions, 62 allergic reactions, and 13 reactions with features of both. Platelet concentrates contained a mean of 0.5 × 10(8) white cells per unit. Lymphocytotoxic antibodies were detectable in 20 of 84 recipients tested proximate to a reaction. Bacterial cultures from 4 of 81 units were positive; 1 unit was associated with fatal Enterobacter sp. sepsis. The incidence of febrile nonhemolytic transfusion reactions but not allergic reactions was related to platelet storage duration. The CCI was not significantly different for transfusions associated with reactions (10.97 [median, range 0–72.5; n = 165]) or not so associated (13.1 [median, range 0–39.5; n = 174]) (p = 0.08). CONCLUSION: The incidence of febrile nonhemolytic transfusion reactions but not allergic reactions appears to be related to the duration of platelet storage. Transfusion reactions may not have an adverse impact on the effectiveness of platelet transfusions.     

Application of nano-LC-based glycomics towards biomarker discovery

The glycome, that is, the glycan components of a biological source, has been widely reported to change with disease states. However, mining the glycome for biomarkers is complicated by glycan structural heterogeneity. Nanoflow LC, or nano-LC, significantly addresses the problem by providing a highly sensitive and quantitative method of separating and profiling glycans. This review summarizes recent advances in analytical technology and methodology that enhance and augment the advantages offered by nano-LC. (e.g., reversed phase, hydrophilic interaction and porous graphitized carbon chromatography, as well as associated derivatization strategies), detectors (e.g., fluorescence and MS), and technology platforms (particularly chip-based nano-LC) are examined in detail, along with their application to biomarker discovery. Particular emphasis is placed on methods and technologies that allow structure-specific glycan profiling.