Background Lipid nanoparticle (LNP) encapsulated self-amplifying RNA (saRNA) is a novel technology formulated as a low dose vaccine against COVID-19.Methods A phase I first-in-human dose-ranging trial of a saRNA COVID-19 vaccine candidate LNP-nCoVsaRNA, was conducted at Imperial Clinical Research Facility, and participating centres in London, UK, between 19 th June to 28 th October 2020. Participants received two intramuscular (IM) injections of LNP-nCoVsaRNA at six different dose levels, 0.1-10.0mg, given four weeks apart. An open-label dose escalation was followed by a dose evaluation. Solicited adverse events (AEs) were collected for one week from enrolment, with follow-up at regular intervals (1-8 weeks). The binding and neutralisation capacity of anti-SARS-CoV-2 antibody raised in participant sera was measured by means of an anti-Spike (S) IgG ELISA, immunoblot, SARS-CoV-2 pseudoneutralisation and wild type neutralisation assays. (The trial is registered: ISRCTN17072692, EudraCT 2020-001646-20).Findings 192 healthy individuals with no history or serological evidence of COVID-19, aged 18-45 years were enrolled. The vaccine was well tolerated with no serious adverse events related to vaccination. Seroconversion at week six whether measured by ELISA or immunoblot was related to dose (both p<0.001), ranging from 8% (3/39; 0.1mg) to 61% (14/23; 10.0mg) in ELISA and 46% (18/39; 0.3mg) to 87% (20/23; 5.0mg and 10.0mg) in a post-hoc immunoblot assay. Geometric mean (GM) anti-S IgG concentrations ranged from 74 (95% CI, 45-119) at 0.1mg to 1023 (468-2236) ng/mL at 5.0mg (p<0.001) and was not higher at 10.0mg. Neutralisation of SARS-CoV-2 by participant sera was measurable in 15% (6/39; 0.1mg) to 48% (11/23; 5.0mg) depending on dose level received.Interpretation Encapsulated saRNA is safe for clinical development, is immunogenic at low dose levels but failed to induce 100% seroconversion. Modifications to optimise humoral responses are required to realise its potential as an effective vaccine against SARS-CoV-2.

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Encephaloceles are one form of neural tube defect and are associated with partial absence of skull bone fusion, with an incidence of 1–4 cases for every 10 000 live births. We report the case of a neonate born at term, with an antenatal diagnosis of occipital encephalocele, which was successfully managed with excision and formation of a reverse visor scalp flap on day 2 of life.Surgery was performed in a single stage, involving a multidisciplinary approach between neurosurgery and plastic surgery teams, with wider management involving neonatal intensive care, paediatric, obstetric and anaesthetic teams.The patient had no early postoperative complications, and we use this case report to demonstrate that a reverse visor scalp flap is a good option to cover full-thickness defects in patients with encephaloceles.Furthermore, we advocate early repair and a multidisciplinary approach to minimise the morbidity associated with occipital encephaloceles.

Epidermal cysts are a common benign skin abnormality, comprising 85-90% of all excised skin cysts. The term epidermal inclusion cyst refers specifically when the cyst resulted from the implantation of epidermal elements in the dermis. Squamous cell carcinomas (SCCs) are common skin lesions; however, a malignant transformation of an epidermal cyst is very rare with incidence of 0.011-0.045%. Few cases of malignant transformation of an epidermal cyst have been reported in the literature so far. This paper presents a case of squamous cell carcinoma arising from a scrotal epidermal cyst.

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