Incomplete surgical excision of keratinocyte skin cancers: a systematic review and meta-analysis.

BACKGROUND: Keratinocyte or nonmelanoma skin cancer (NMSC) is the commonest malignancy worldwide. The usual treatment is surgical excision. Current guidelines underestimate incomplete excision rates. OBJECTIVES: We aimed to determine the risk of incomplete excision of NMSCs through a systematic review and meta-analysis of primary clinical studies. METHODS: A PRISMA-compliant systematic review and meta-analysis was performed using methodology proposed by Cochrane (PROSPERO CRD42019157936). A comprehensive search strategy was applied to MEDLINE, Embase, Scopus, CINAHL, EMCare, Cochrane Library and the grey literature (January 2000-27 November 2019). All studies were included except those on Mohs micrographic surgery, frozen section or biopsies. Abstract screening and data extraction were performed in duplicate. Risk of bias was assessed using a tool for prevalence/incidence studies. The primary outcome was the proportion of incomplete surgical excisions. A random-effects model for pooling of binomial data was used. Differences between proportions were assessed by subgroup meta-analysis and meta-regression, which were presented as risk ratios (RRs). RESULTS: Searching identified 3477 records, with 110 studies included, comprising 53 796 patients with 106 832 basal cell carcinomas (BCCs) and 21 569 squamous cell carcinomas (SCCs). The proportion of incomplete excisions for BCC was 11·0% [95% confidence interval (CI) 9·7-12·4] and for SCC 9·4% (95% CI 7·6-11·4). Proportions of incomplete excisions by specialty were: dermatology, BCCs 6·2% and SCCs 4·7%; plastic surgery, BCCs 9·4% and SCCs 8·2%; general practitioners, BCCs 20·4% and SCCs 18·9%. The risk of incomplete excision for general practitioners was four times that of dermatologists for both BCCs (RR 3·9, 95% CI 2·0-7·3) and SCCs (RR 4·8, 95% CI 1·0-22·8). Studies were heterogeneous (I2  = 98%) and at high risk of bias. CONCLUSIONS: The proportion of incomplete excisions is higher than previously reported. Excisions performed by specialists may lower the risk of incomplete excision.

Vitamin K status and inflammation are associated with cognition in older Irish adults.

Studies have shown associations between reduced vitamin K status and poor cognitive function. However, despite this apparent link, direct studies measuring cognitive function, vitamin K status and inflammation are lacking. In the current study, The ELDERMET cohort was investigated to identify associations between cognition, vitamin K status and inflammation. The primary aim of the ELDERMET study was to investigate the relationship between gut bacteria, diet, lifestyle and health in 500 older Irish adults. Significant differences in serum phylloquinone, dietary phylloquinone and inflammatory markers were found across varying levels of cognitive function, after controlling for sex, age, body mass index (BMI), triglycerides and blood pressure. In addition, significantly higher levels of dietary phylloquinone were found in those with better cognition compared to those with the poorest function. Higher levels of inflammatory were also associated with poor cognition. Furthermore, both dietary and serum phylloquinone were significant independent predictors of good cognitive function, after controlling for confounders. This study highlights the importance of dietary vitamin K as a potentially protective cognitive factor; it also provides evidence for the correlation between cognition and inflammation. Strategies should be devised by which elderly populations can access rich dietary sources of phylloquinone to maintain cognition.

Exploring the putative role of kallikrein-6, calpain-1 and cathepsin-D in the proteolytic degradation of α-synuclein in multiple system atrophy.

AIMS: There is evidence that accumulation of α-synuclein (α-syn) in Parkinson's disease (PD) and dementia with Lewy bodies (DLB) results from impaired removal of α-syn rather than its overproduction. Kallikrein-6 (KLK6), calpain-1 (CAPN1) and cathepsin-D (CTSD) are among a small number of proteases that cleave α-syn and are dysregulated in PD and DLB. Our aim in this study was to determine whether protease activity is altered in another α-synucleinopathy, multiple system atrophy (MSA), and might thereby modulate the regional distribution of α-syn accumulation. METHODS: mRNA and protein level and/or activity of KLK6, CAPN1 and CTSD were measured and assessed in relation to α-syn load in multiple brain regions (posterior frontal cortex, caudate nucleus, putamen, occipital cortex, pontine base and cerebellar white matter), in MSA (n = 20) and age-matched postmortem control tissue (n = 20). RESULTS: CTSD activity was elevated in MSA in the pontine base and cerebellar white matter. KLK6 and CAPN1 levels were elevated in MSA in the putamen and cerebellar white matter. However, the activity or level of these proteolytic enzymes did not correlate with the regional distribution of α-syn. CONCLUSIONS: Accumulation of α-syn in MSA is not due to reduced activity of the proteases we have studied. We suggest that their upregulation is likely to be a compensatory response to increased α-syn in MSA.

Satisfaction rates with the current Special Type Consultation (STC) reimbursement scheme among General Practitioners - A Mixed Methods Study.

The Special Type Consultation (STC) scheme is a fee-for-service reimbursement scheme for General Practitioners (GPs) in Ireland. Introduced in 1989, the scheme includes specified patient services involving the application of a learned skill, e.g. suturing. This study aims to establish the extent to which GPs believe this scheme is appropriate for current General Practice. This is an embedded mixed-methods study combining quantitative data on GPs working experience of and qualitative data on GPs attitudes towards the scheme. Data were collected by means of an anonymous postal questionnaire. The response rate was 60.4% (n=159.) Twenty-nine percent (n=46) disagreed and 65% (n=104) strongly disagreed that the current list of special items is satisfactory. Two overriding themes were identified: economics and advancement of the STC process. This study demonstrates an overwhelming consensus among GPs that the current STC scheme is outdated and in urgent need of revision to reflect modern General Practice.

Sun exposure and sun protection practices of children and their parents.

The primary aims of this study were: to estimate sun exposure in hours of children in Cork during the summer months; to examine sun protection measures used by children and their parents and to explore parental knowledge of sun exposure and protection. A cross-sectional study, using a semi-structured questionnaire, was conducted in June 2006 in primary schools, pre-schools and creches throughout Cork City and County. Parents of 250 children aged less than 12 years were sampled. Mean sun exposure of Cork children was 40.9 hours per week in the summer months, with 77 (46.1%) children developing sunburn. 59.3% of the studied children were of skin type 1 or 2. 95 (57%) children on weekdays and 137 (82%) children at weekends were exposed to the sun between 11 am and 3 pm. Sunscreen and hats/caps were the most common protection measures used. A minority used protective clothing, sunglasses or sought shade. Thirty one (30.5%) children had sunscreen reapplied every 2 hours. Knowledge of sun protection was considerable among Irish parents. However the frequency of sunburn among Irish children suggests we are not providing them with adequate sun protection.

Amino acid metabolism, insulin secretion and diabetes.

In addition to the primary stimulus of glucose, specific amino acids may acutely and chronically regulate insulin secretion from pancreatic beta-cells in vivo and in vitro. Mitochondrial metabolism is crucial for the coupling of glucose, alanine, glutamine and glutamate recognition with exocytosis of insulin granules. This is illustrated by in vitro and in vivo observations discussed in the present review. Mitochondria generate ATP (the main coupling messenger in insulin secretion) and other factors that serve as sensors for the control of the exocytotic process. The main factors that mediate the key amplifying pathway over the Ca(2+) signal in nutrient-stimulated insulin secretion are nucleotides (ATP, GTP, cAMP and NADPH), although metabolites have also been proposed, such as long-chain acyl-CoA derivatives and glutamate. In addition, after chronic exposure, specific amino acids may influence gene expression in the beta-cell, which have an impact on insulin secretion and cellular integrity. Therefore amino acids may play a direct or indirect (via generation of putative messengers of mitochondrial origin) role in insulin secretion.

Toxicity and cerebrospinal fluid levels of carboplatin chronically infused into the brainstem of a primate.

PURPOSE: Carboplatin was infused into the brainstem of cynomolgus monkeys to investigate neurotoxicity and systemic exposures following chronic local delivery. METHODS: Infusions at 0.42 microl/h were intended to deliver 0.025 (n = 2), 0.075 (n = 3), 0.25 (n = 5), and 0.75 (n = 3) mg/kg by day 30. Laboratory tests, radiographic measurements, and clinical observations were used to monitor toxicity. Blood and cerebrospinal fluid (CSF) were sampled for platinum. RESULTS: Lethargy and ataxia were observed after week 4 in the monkeys given 0.075 mg/kg, and week 2 in the monkeys given 0.25 mg/kg when the infused doses were approximately 250 and 400 microg, respectively. Rapidly progressive neurotoxicity with the 0.75 mg/kg dose required termination of the infusions at days 4-10. Hematology and chemistry values were unremarkable in all groups. Blood levels of platinum remained undetectable in 0.025 and 0.075 mg/kg dose groups. Levels in the 0.25 mg/kg group were 3.1 +/- 0.6 microg/l at 2 weeks and 5.2 +/- 0.8 microg/l at 1 month. The CSF platinum levels varied. Animals in the 0.25 mg/kg group had higher CSF levels at 2 weeks (avg. 65 microg/l, range 36-89) compared to their 1 month value (avg. 60 microg/l, range 7-170), despite the constant infusion. CONCLUSION: Carboplatin can be chronically infused into monkey brainstems. Neurotoxicity is the predominant side effect and is dose-dependent. Pharmacokinetics of local and systemic delivery are different for carboplatin. Further studies are needed to monitor toxicity at higher flow rates and to investigate drug binding to abnormal central nervous system (CNS) tissues.