Appraisal of International Guidelines for Cutaneous Melanoma Management using the AGREE II assessment tool.

BACKGROUND: The evidence base behind new melanoma treatments is rapidly accumulating. This is not necessarily reflected in current guidance. A recent UK-based expert consensus statement, published in JPRAS, has called for updates to the widely accepted 2015 National Institute for Health and Care Excellence (NICE) guideline for melanoma (NG14). We aimed to compare the quality of NG14 to all other melanoma guidelines published since. METHODS: We conducted a systematic search of PubMed, Medline, and online clinical practice guideline databases to identify melanoma guidelines published between 29th July 2015 and 23rd August 2021 providing recommendations for adjuvant treatment, radiotherapy, surgical management, or follow-up care. Three authors independently assessed the quality of identified guidelines using the Appraisal of Guidelines for Research & Evaluation Instrument II (AGREE II) assessment tool, which measures six domains of guideline development. Inter-rater reliability was assessed by Kendall's coefficient of concordance (W). RESULTS: Twenty-nine guidelines were included and appraised with excellent concordance (Kendall's W for overall guideline score 0.88, p<0.001). Overall, melanoma guidelines scored highly in the domains of 'Scope and purpose' and 'Clarity of presentation', but poorly in the 'Applicability' domain. The NICE guideline on melanoma (NG14) achieved the best overall scores. CONCLUSION: Melanoma treatment has advanced since NG14 was published, however, the NICE melanoma guideline is of higher quality than more recent alternatives. The planned update of NG14 in 2022 is in demand.

Zika virus impairs the development of blood vessels in a mouse model of congenital infection.

Zika virus (ZIKV) is associated with brain development abnormalities such as primary microcephaly, a severe reduction in brain growth. Here we demonstrated in vivo the impact of congenital ZIKV infection in blood vessel development, a crucial step in organogenesis. ZIKV was injected intravenously in the pregnant type 2 interferon (IFN)-deficient mouse at embryonic day (E) 12.5. The embryos were collected at E15.5 and postnatal day (P)2. Immunohistochemistry for cortical progenitors and neuronal markers at E15.5 showed the reduction of both populations as a result of ZIKV infection. Using confocal 3D imaging, we found that ZIKV infected brain sections displayed a reduction in the vasculature density and vessel branching compared to mocks at E15.5; altogether, cortical vessels presented a comparatively immature pattern in the infected tissue. These impaired vascular patterns were also apparent in the placenta and retina. Moreover, proteomic analysis has shown that angiogenesis proteins are deregulated in the infected brains compared to controls. At P2, the cortical size and brain weight were reduced in comparison to mock-infected animals. In sum, our results indicate that ZIKV impairs angiogenesis in addition to neurogenesis during development. The vasculature defects represent a limitation for general brain growth but also could regulate neurogenesis directly.