Soluble CD40 ligand accumulates in stored blood components, primes neutrophils through CD40, and is a potential cofactor in the development of transfusion-related acute lung injury

Transfusion-related acute lung injury (TRALI) is a form of posttransfusion acute pulmonary insufficiency that has been linked to the infusion of biologic response modifiers (BRMs), including antileukocyte antibodies and lipids. Soluble CD40 ligand (sCD40L) is a platelet-derived proinflammatory mediator that accumulates during platelet storage. We hypothesized that human polymorpho-nuclear leukocytes (PMNs) express CD40, CD40 ligation rapidly primes PMNs, and sCD40L induces PMN-mediated cytotoxicity of human pulmonary microvascular endothelial cells (HMVECs). Levels of sCD40L were measured in blood components and in platelet concentrates (PCs) implicated in TRALI or control PCs that did not elicit a transfusion reaction. All blood components contained higher levels of sCD40L than fresh plasma, with apheresis PCs evidencing the highest concentration of sCD40L followed by PCs from whole blood, whole blood, and packed red blood cells (PRBCs). PCs implicated in TRALI reactions contained significantly higher sCD40L levels than control PCs. PMNs express functional CD40 on the plasma membrane, and recombinant sCD40L (10 ng/mL-1 mug/mL) rapidly (5 minutes) primed the PMN oxidase. Soluble CD40L promoted PMN-mediated cytotoxicity of HMVECs as the second event in a 2-event in vitro model of TRALI. We concluded that sCD40L, which accumulates during blood component storage, has the capacity to activate adherent PMNs, causing endothelial damage and possibly TRALI in predisposed patients.     

To transfer or not to transfer: Aged care nurses’ decision-making in transferring residents to the emergency department

BackgroundNurses are key decision makers in residential aged care facilities and play a significant role in the transfer of residents from residential aged care facilities to emergency departments. There is scant literature about the role of nurses in the transfer decision-making process.AimTo describe the experiences of residential aged care facility nurses who engage in decision-making to transfer residents to emergency department.MethodsThis research has adopted interpretive qualitative approach of phenomenography. In-depth interviews were undertaken with 20 residential aged care facility nurses across two sites. Uniquely, drawing was used as one way to collect rich, textured data in these in-depth interviews.FindingsSix categories emerged to represent residential aged care facility nurses’ conceptions of decision-making about transferring a resident to the emergency department: “Being a marionette”; “Too dumb to have an opinion”; “Making the family happy”; “Not about the resident”; “Having experience”; and “Being on your own”.DiscussionResidential aged care facility nurses experienced decision-making as not being able to do what is right for the resident most of the time due to a myriad of factors, with heavy influence of other key stakeholders.ConclusionDecision-making is described as a professional responsibility wherein residential aged care facility nurses face dilemmas related to the transfer of a resident to the emergency department and perceived as a constraint.     

A normal ovary in an abnormal location: A case of torsion

The clinical and radiologic diagnosis of adnexal torsion is challenging. The patient's history, physical examination, and laboratory evaluation may overlap significantly with other causes of abdominal pain. Ultrasound is the most common radiologic tool to assess for torsion, and the imaging findings can be equally equivocal. We present a case of adnexal torsion in an 18‐year‐old emergency room patient with abdominal pain, diagnosed by ultrasound based solely on an abnormal medial position of the ovary–a finding that has been only rarely mentioned in the literature, and never in isolation. © 2014 Wiley Periodicals, Inc. J Clin Ultrasound 43 :578–580, 2015     

Differential Association Between HDL Subclasses and the Development of Type 2 Diabetes in a Prospective Study of Japanese Americans

OBJECTIVERecent studies have suggested that HDL cholesterol is inversely associated with the development of type 2 diabetes. However, little is known about the association between different HDL subclasses and the risk for future type 2 diabetes.RESULTSIn univariate analysis, total HDL and HDL2 cholesterol were inversely associated with the incidence of type 2 diabetes, but HDL3 cholesterol was not. In multivariate analysis, total HDL cholesterol (odds ratio per 1-SD increment, 0.72 [95% CI 0.52–0.995], P = 0.047) and HDL2 cholesterol (odds ratio per 1-SD increment, 0.64 [95% CI 0.44–0.93], P = 0.018) were inversely associated with the risk for type 2 diabetes independent of age, sex, BMI, waist circumference, family history of diabetes, lifestyle factors, systolic blood pressure, lipid-lowering medication use, triglyceride level, HOMA-insulin resistance, and 2-h glucose; however, HDL3 cholesterol was not associated with diabetes risk. The association between diabetes risk and total HDL and HDL2 cholesterol became insignificant after adjustment for VAT area.CONCLUSIONSSubjects with higher HDL2 cholesterol were at lower risk for incident type 2 diabetes, but this association was confounded by and not independent of VAT. Higher HDL3 cholesterol was not associated with diabetes risk.     

A human strain of Oxalobacter (HC-1) promotes enteric oxalate secretion in the small intestine of mice and reduces urinary oxalate excretion

Enteric oxalate secretion that correlated with reductions in urinary oxalate excretion was previously reported in a mouse model of primary hyperoxaluria, and in wild type (WT) mice colonized with a wild rat strain (OXWR) of Oxalobacter (Am J Physiol 300:G461–G469, 2010). Since a human strain of the bacterium is more likely to be clinically used as a probiotic therapeutic, we tested the effects of HC-1 in WT. Following artificial colonization of WT mice with HC-1, the bacteria were confirmed to be present in the large intestine and, unexpectedly, detected in the small intestine for varying periods of time. The main objective of the present study was to determine whether the presence of HC-1 promoted intestinal secretion in the more proximal segments of the gastrointestinal tract. In addition, we determined whether HC-1 colonization led to reductions in urinary oxalate excretion in these mice. The results show that the human Oxalobacter strain promotes a robust net secretion of oxalate in the distal ileum as well as in the caecum and distal colon and these changes in transport correlate with the beneficial effect of reducing renal excretion of oxalate. We conclude that OXWR effects on intestinal oxalate transport and oxalate homeostasis are not unique to the wild rat strain and that, mechanistically, HC-1 has significant potential for use as a probiotic treatment for hyperoxaluria especially if it is also targeted to the upper and lower gastrointestinal tract.     

Imaging of pediatric adrenal tumors: A COG Diagnostic Imaging Committee/SPR Oncology Committee White Paper

Adrenal tumors other than neuroblastoma are uncommon in children. The most frequently encountered are adrenocortical carcinoma and pheochromocytoma. This paper offers consensus recommendations for imaging of pediatric patients with a known or suspected primary adrenal malignancy other than neuroblastoma at diagnosis and during follow-up.