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.
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’.
We present the case of a 34-year old woman who initially presented with obesity and back pain. She was eventually diagnosed with Cushing's syndrome secondary to an adrenocortical carcinoma that had metastasised to her spine, causing cauda equina compression. The delays in reaching the correct diagnosis caused significant morbidity and exemplify the pitfalls of premature closing, a common cognitive error in diagnostic reasoning. KEYWORDS :Cushing's syndrome , adrenocortical carcinoma , cauda equina , back pain , premature closing Case reportA 34-year-old woman presented to the emergency department with severe central lower back pain and paraplegia. The back pain had started after her bed collapsed two months previously and had since been steadily worsening. She had recently visited her general practitioner who diagnosed mechanical back pain secondary to obesity and prescribed simple analgesics. She had visited a chiropractor four days previously and also attended the emergency department at another hospital two days before. On that occasion, examination identified tender lower thoracic and lumbar vertebrae and paraspinal muscles, but a full neurological examination was not carried out ('pain limited examination'). The diagnosis of musculoskeletal back pain secondary to morbid obesity was made and the patient discharged with a plan for outpatient lumbar radiographs. On presentation to our institution, she had been unable to walk for six days.The patient reported significant weight gain over the preceding 18 months (from clothing size 16 to 28) and now weighed 172 kg. She reported low mood and amenorrhoea over the last 12 months. She had been prescribed sertraline for depression and furosemide for lower limb oedema. Blood tests performed a few months before had shown low folliclestimulating hormone (<0.2 U/L; normal range, 2.9-8.4 U/L) and luteinising hormone (<0.2 U/L; normal range, 1.3-8.4 U/L) with mildly elevated thyroid stimulating hormone (6.44 mU/L; ABSTRACT normal range, 0.35-5.50 mU/L), but these findings were not investigated further. On examination, there was evidence of centripetal obesity, proximal muscle wasting with a prominent interscapular fat pad and hirsutism. Her blood pressure was 144/64 mmHg, pulse rate 80 bpm, respiratory rate 16 breaths/min and oxygen saturations 98% on air. Full neurological examination revealed normal cranial nerves; bilateral proximal myopathy in the upper limbs (4/5), decreased power throughout the lower limbs (3/5) with normal sensation, including perineal sensation, and symmetrical 2+ knee reflexes with downgoing planters bilaterally. She was unable to stand.Blood tests revealed haemoglobin 130 g/L (normal range 115-160), mean corpuscular volume 60 fL (normal range 80-100), Na 138 mmol/L (normal range 133-146), K 4.1 mmol/L (normal range 3.5-5.3) and CCa 2.70 mmol/L (normal range 2.20-2.60). An urgent magnetic resonance image of the whole spine showed extensive vertebral bony metastases with fracture at L2 causing cauda equina compression (Fig 1 ). Whole body computeri...
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.
Metastatic pancreatic neuroendocrine tumourA 46-year-old male was referred to his local hospital with palpitations and a 6-month history of severe watery diarrhoea associated with weight loss; nausea; profound, refractory hypokalaemia (Potassium 2.6, NR 3.5-5.3 mmol/l); and acute kidney injury. Bowel motions were large-volume, watery, and passed up to 10 times per day, with the absence of blood or mucous. He had no symptoms of flushing or wheezing, nor symptoms suggestive of hypo-or hyperglycaemia; however, reported a transient 'eczema-like' rash which resolved with later systemic treatment.Figure 1 shows a near-diagnostic image from CT imaging, which reveals a lesion within the tail of an atrophic pancreas, with multiple hepatic metastases. It also demonstrates distended small and large bowel with fluid levels consistent with secretory diarrhoea. Liver lesions were octreotide-avid on octreoscan. Vasoactive Intestinal Polypeptide (VIP) was 784 (0-30 pmol/l), glucagon 682 (0-50 pmol/l), chromogranin A 268 (0-60 pmol/l), chromogranin B 303 (0-150 pmol/l) and pancreatic polypeptide 1972 (0-300 pmol/l). Urinary 5-hydroxyindoleacetic acid was elevated at 66 (0-50 mmmol/24 h). Histology on liver biopsy was of a welldifferentiated grade 1 neuroendocrine tumour.A diagnosis of metastatic functioning pancreatic neuroendocrine tumour co-secreting VIP and glucagon was made. The rash was thought to be necrolytic migratory erythema.This patient is being treated with life-long somatostatin analogue therapy (lanreotide 120 mg subcutaneously every 28 days, with 100 mg octreotide as required for diarrhoea). This treatment has resulted in full resolution of gastrointestinal symptoms and follow-up imaging at 6 months demonstrated stable disease with resolution of previous bowel findings. He remains under close review.
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