Pseudomonas aeruginosa meningitis and ventriculitis are predominantly nosocomial and related to prior neurosurgery. It can be difficult to diagnose as CSF Gram-film and meningism are insensitive markers. Appropriate empirical treatment, neurosurgical prophylaxis and surveillance can aid in managing this infection.

Sunlight stimulates a multitude of important biological effects on skin, causing, amongst other pathological changes, photocarcinogenesis. Sunscreens are designed to provide protection against these harmful properties of ultraviolet radiation, and public health campaigns have been employed to encourage their use. Despite this, there has been a continued rise in the incidence and mortality of the most harmful skin cancer, malignant melanoma. This review article therefore looks at the role of ultraviolet radiation in causing skin cancer; summarizes the available evidence on both the beneficial and harmful effects of sunscreen use; and concludes with practical advice on how we might advise our patients to best protect themselves from photocarcinogenesis.

IntroductionEDP1815 is a non-colonizing pharmaceutical preparation of a single stain of Prevotella histicola isolated from the duodenum of a human donor. We report here preclinical and clinical studies showing that the action of EDP1815, an orally delivered and gut restricted single strain of commensal bacteria can regulate inflammatory responses throughout the body.MethodsSupported by evidence for anti-inflammatory activity in three preclinical mouse models of Th1-, TH2-, and Th17-mediated inflammation, EDP1815 was tested clinically in three Phase 1b studies in patients with psoriasis, patients with atopic dermatitis, and healthy volunteers in a KLH skin challenge model.ResultsPreclinically, EDP1815 was efficacious in all three mouse models of inflammation, showing reduction in skin inflammation as well as related tissue cytokines. In the Phase 1b studies, EDP1815 was found to be well tolerated by participants, with a safety profile comparable to placebo, including no severe or consistent side-effects reported, and no evidence of immunosuppression with no opportunistic infection occurring in these studies. In psoriasis patients, signs of clinical efficacy were seen after 4 weeks of treatment, which continued beyond the treatment period in the higher-dose cohort. In atopic dermatitis patients, improvements were seen throughout the key physician-and patient-reported outcomes. In a healthy-volunteer study of a KLH-induced skin inflammatory response, consistent anti-inflammatory effects were seen in two cohorts through imaging-based measures of skin inflammation.DiscussionThis is the first report demonstrating clinical effects from targeting peripheral inflammation with a non-colonizing gut-restricted single strain of commensal bacteria, providing proof of concept for a new class of medicines. These clinical effects occur without systemic exposure of EDP1815 or modification of the resident gut microbiota, and with placebo-like safety and tolerability. The breadth of these clinical effects of EDP1815, combined with its excellent safety and tolerability profile and oral administration, suggests the potential for a new type of effective, safe, oral, and accessible anti-inflammatory medicine to treat the wide range of diseases driven by inflammation.Clinical Trial Registration: EudraCT # 2018-002807-32; EudraCT # 2018-002807-32; NL8676; https://clinicaltrials.gov/ct2/show/NCT03733353; http://www.trialregister.nl.

Summary Aim Rueter et al. aimed to ‘determine the effects of early postnatal vitamin D supplementation on infant eczema and immune development’. Setting and design This was a double‐blind randomized placebo‐controlled trial with an additional nonrandomized exploratory analysis on the effects of ultraviolet (UV) exposure led from a hospital setting. Study exposure Vitamin D (400 iU daily) drops or placebo drops (coconut and palm kernel oil) were allocated randomly to 195 infants born to families with a first‐degree relative with atopic disease. Eighty‐six of these infants were allocated personal UV dosimeters in a nonrandomized fashion to measure UV light (290–380 nm) exposure until 3 months of age. Outcomes Eczema and wheeze were assessed at 3 and 6 months, and 25 immune function markers were assessed at 6 months of age. Infant vitamin D levels and immune functions were measured at 6 months of age. Results Although vitamin D levels were significantly greater in infants in the intervention group than in those in the placebo group at 3 and 6 months of age, there was no difference in eczema between groups at either time point (10·0% vs. 6·7% at 3 months and 21·8 vs. 19·3% at 6 months for the vitamin D and placebo groups, respectively). In the subset of infants given a dosimeter, those with eczema had less UV light exposure (median 555 J m−2) than infants who did not develop eczema (median 998 J m−2). Across the 25 immune functions, UV light exposure was inversely correlated with interleukin‐2, granulocyte macrophage colony‐stimulating factor and eotaxin production by Toll‐like receptor ligands. Conclusions Vitamin D supplementation in high‐risk infants increased vitamin D levels but did not reduce eczema. Exploratory post‐hoc analyses in a nonrandomized subset showed an association between greater direct UV light exposure and reduction of eczema. The authors claim that their ‘findings indicate that UV light exposure appears more beneficial than vitamin D supplementation as an allergy prevention strategy in early life’.