The latitude-dependent autoimmune disease risk genes ZMIZ1 and IRF8 regulate mononuclear phagocytic cell differentiation in response to vitamin D.

Epidemiological, molecular and genetic studies have indicated that high serum vitamin D levels are associated with lower risk of several autoimmune diseases. The vitamin D receptor (VDR) binding sites in monocytes and dendritic cells (DCs) are more common in risk genes for diseases with latitude dependence than in risk genes for other diseases. The transcription factor genes Zinc finger MIZ domain-containing protein 1 (ZMIZ1) and interferon regulatory factor 8 (IRF8)-risk genes for many of these diseases-have VDR binding peaks co-incident with the risk single nucleotide polymorphisms (SNPs). We show these genes are responsive to vitamin D: ZMIZ1 expression increased and IRF8 expression decreased, and this response was affected by genotype in different cell subsets. The IL10/IL12 ratio in tolerogenic DCs increased with vitamin D. These data indicate that vitamin D regulation of ZMIZ1 and IRF8 in DCs and monocytes contribute to latitude-dependent autoimmune disease risk.

Optimal cancer care pathways - the ideal versus reality for patient-centric cancer care during COVID-19.

Objectives To assess whether compliance with the nationally endorsed Optimal Care Pathways is evident in 75% of patients treated with curative intent treatment and if this compliance was impacted by the COVID-19 pandemic (hereinafter COVID-19). Methods This retrospective study included patients undergoing curative treatment with radiotherapy in head and neck (HN), breast, lung and gastrointestinal malignancies between January 2019 and June 2021 in a single NSW outer metropolitan cancer service. For care delivered within the remit of cancer services, the primary outcome measure was the proportion of patients whose treatment complied with the Optimal Care Pathways recommended time frame. Secondary outcome measures included evaluating the effect of COVID-19 on the proportion of patients being treated within the recommended time frame. Results There were n = 733 eligible patients across the five tumour streams with the majority being breast cancer patients comprising 65% (n = 479) of the cohort, followed by HN cancer patients (n = 125, 17%). None of the tumour subsites abided by the 75% compliance rate. Oesophageal cancer patients had the lowest compliance rate of 4% (P < 0.001), with a similarly low compliance rate for rectal cancer patients at 33% (P = 0.002). None of the hypothesis tests to assess for detriment in treatment time during COVID-19 were statistically significant (P > 0.05). Conclusion Despite the availability of best practice guidelines, there is limited compliance throughout all cancer subtypes, which has not been negatively influenced by COVID-19. Improved awareness of the Optimal Care Pathways, and implementation of the associated infrastructure and systems, are required to support compliance.