Clinical management of contrast-induced neurotoxicity: a systematic review.

BACKGROUND: Contrast-induced neurotoxicity (CIN) is an increasingly recognised complication following endovascular procedures utilising contrast. It remains poorly understood with heterogenous clinical management strategies. The aim of this review was to identify commonly employed treatments for CIN to enhance clinical decision making. METHODS: A systematic search of Embase (1947-2022) and Medline (1946-2022) was conducted. Articles describing (i) patients with a clinical diagnosis of CIN, (ii) with radiological exclusion of other pathologies, (iii) detailed report of treatments, and (iv) discharge outcomes, were included. Data relating to demographics, procedure, symptoms, treatment and outcomes were extracted. RESULTS: A total of 73 patients were included, with a median age of 64 years. The most common procedures were cerebral angiography (42.5%) and coronary angiography (42.5%), and the median volume of contrast administered was 150 ml. The most common symptoms were cortical blindness (38.4%) and reduced consciousness (28.8%), and 84.9% of patients experienced complete resolution at the time of discharge. Management included intravenous fluids to dilute contrast in the cerebrovasculature (54.8%), corticosteroids to reduce blood-brain barrier damage (47.9%), antiseizure (16.4%) and sedative (16.4%) medications. Mannitol (13.7%) was also utilised to reduce cerebral oedema. Intensive care admission was required for 19.2% of patients. No statistically significant differences were observed between treatment and discharge outcomes. CONCLUSIONS: The clinical management of CIN should be considered on a patient-by-patient basis, but may consist of aggressive fluid therapy alongside corticosteroids, as well as other supportive therapy as required. Further examination of CIN management is required to define best practice.

Smith-specific regulatory T cells halt the progression of lupus nephritis.

Antigen-specific regulatory T cells (Tregs) suppress pathogenic autoreactivity and are potential therapeutic candidates for autoimmune diseases such as systemic lupus erythematosus (SLE). Lupus nephritis is associated with autoreactivity to the Smith (Sm) autoantigen and the human leucocyte antigen (HLA)-DR15 haplotype; hence, we investigated the potential of Sm-specific Tregs (Sm-Tregs) to suppress disease. Here we identify a HLA-DR15 restricted immunodominant Sm T cell epitope using biophysical affinity binding assays, then identify high-affinity Sm-specific T cell receptors (TCRs) using high-throughput single-cell sequencing. Using lentiviral vectors, we transduce our lead Sm-specific TCR into Tregs derived from patients with SLE who are anti-Sm and HLA-DR15 positive. Compared with polyclonal mock-transduced Tregs, Sm-Tregs potently suppress Sm-specific pro-inflammatory responses in vitro and suppress disease progression in a humanized mouse model of lupus nephritis. These results show that Sm-Tregs are a promising therapy for SLE.