PEGylated Liposomes for Diagnosis of Polyethylene Glycol Allergy.

BACKGROUND: Polyethylene glycol (PEG) is a non-protein polymer that is present in its native (unbound) form as an excipient in a range of products, and is increasingly being utilised clinically in the form of PEGylated liposomal medications and vaccines. PEG is the cause of anaphylaxis in a small percentage of drug reactions, however diagnosis of PEG allergy is complicated by the variable and poor diagnostic performance of current skin testing protocols. OBJECTIVE: We assessed the diagnostic performance of PEGylated lipid medications as an alternative to currently described tests that use medications containing PEG excipients. METHODS: Nine patients with a strong history of PEG allergy were evaluated by skin testing with a panel of PEG-containing medications, and with a PEGylated lipid nanoparticle vaccine (BNT162b2). Reactivity of basophils to unbound and liposomal PEG was assessed ex vivo, and specificity of basophil responses to PEGylated liposomes was investigated with a competitive inhibition assay. For detailed Methods, please see the Methods section in this article's Online Repository. RESULTS: Despite compelling histories of anaphylaxis to PEG-containing medications, only two out of nine patients (22%) returned a positive skin test to purified PEG or their index-reaction indicated PEG-containing compound. Conversely, nine out of nine patients (100%) were skin test positive or basophil activation test positive to PEGylated liposomal BNT162b2 vaccine. Concordantly, PEGylated liposomal drugs (BNT162b2 vaccine and PEGylated liposomal doxorubicin), but not purified PEG2000, consistently induced basophil activation ex vivo in patients with PEG allergy but not in non-allergic controls. Basophil reactivity to PEGylated nanoparticles competitively inhibited by pre-incubation of basophils with native PEG2000. CONCLUSION: We demonstrate that presentation of PEG on the surface of a lipid nanoparticle increases its in vivo and ex vivo allergenicity, and improves diagnosis of PEG allergy.

Negative Vaccination Strategies for Promotion of Transplant Tolerance.

Organ transplantation requires the use of immunosuppressive medications that lack antigen specificity, have many adverse side effects, and fail to induce immunological tolerance to the graft. The safe induction of tolerance to allogeneic tissue without compromising host responses to infection or enhancing the risk of malignant disease is a major goal in transplantation. One promising approach to achieve this goal is based on the concept of "negative vaccination." Vaccination (or actively acquired immunity) involves the presentation of both a foreign antigen and immunostimulatory adjuvant to the immune system to induce antigen-specific immunity. By contrast, negative vaccination, in the context of transplantation, involves the delivery of donor antigen before or after transplantation, together with a "negative adjuvant" to selectively inhibit the alloimmune response. This review will explore established and emerging negative vaccination strategies for promotion of organ or pancreatic islet transplant tolerance. These include donor regulatory myeloid cell infusion, which has progressed to early-phase clinical trials, apoptotic donor cell infusion that has advanced to nonhuman primate models, and novel nanoparticle antigen-delivery systems.

Atherosclerotic Vascular Disease Associated with Chronic Kidney Disease.

Cardiovascular risk increases as glomerular filtration rate (GFR) declines in progressive renal disease and is maximal in patients with end-stage renal disease requiring maintenance dialysis. Atherosclerotic vascular disease, for which hyperlipidemia is the main risk factor and lipid-lowering therapy is the key intervention, is common. However, the pattern of dyslipidemia changes with low GFR and the association with vascular events becomes less clear. While the pathophysiology and management of patients with early chronic kidney disease (CKD) is similar to the general population, advanced and end-stage CKD is characterized by a disproportionate increase in fatal events, ineffectiveness of statin therapy, and greatly increased risk associated with coronary interventions. The most effective strategies to reduce atherosclerotic cardiovascular disease in CKD are to slow the decline in renal function or to restore renal function by transplantation.

Efforts to Attenuate the Spread of Infection (EASI): a prospective, observational multicentre survey of ultrasound equipment in Australian emergency departments and intensive care units.

BACKGROUND AND OBJECTIVES: Ultrasound is a common and necessary part of acute care medicine, but may present an infection risk to patients secondary to transfer of infectious agents between patients. Our primary objective was to detect blood contamination on ultrasound equipment in emergency departments (EDs) and intensive care units. Secondary objectives included detection of microbial contamination and determination of factors associated with contamination. DESIGN AND SETTING: We tested ultrasound equipment used in five EDs and five ICUs for blood and microbial contamination, and collated and analysed contamination data using tables and multiple logistic regression. MAIN OUTCOME MEASURES AND RESULTS: We performed 109 tests for blood and 131 tests for microbial contamination, with 61% of samples testing positive for blood contamination (95% CI, 52%-71%) and 48% testing positive for microbiological contamination (95% CI, 40%-57%). Transducer leads and transducers had high blood contamination (88% and 57%, respectively) and microbiological contamination (62% and 46%, respectively). Equipment from ICUs was less likely to test positive (odds ratio, 0.55; 95% CI, 0.37-0.79). Only 51% of blood-contaminated samples were visibly stained, and visible staining was not associated with microbiological contamination (57%; P=1). CONCLUSION: Our results show significant contamination of ultrasound equipment, and that visual inspection of equipment is neither sufficient nor reliable in excluding contamination. Ultrasound equipment is a possible factor in the transmission of infectious diseases in EDs and ICUs. Guidelines must be formulated, disseminated and rapidly adopted to ensure the safety of the most acutely ill patients exposed to ultrasound procedures in acute care settings.