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The article focuses on a study conducted to evaluate safety, complications and patients' acceptance of Mohs micrographic surgery under local anaesthesia. Topics discussed include specimens, Mohs micrographic surgery (MMS) is regarded as the gold-standard surgical treatment of high-risk nonmelanoma skin cancers, patients tolerate tumour extirpation and subsequent reconstruction under local anaesthesia and difference in patient satisfaction between patients declared clear of tumour.

A 2-year whole-farm system study compared the accumulation, utilization and nutritive value of grass in spring-calving grass-based systems differing in stocking rate ( SR) and calving date ( CD). Six treatments (systems) were compared over two complete grazing seasons. Stocking rates used in the study were low (2·5 cows ha−1), medium (2·9 cows ha−1) and high (3·3 cows ha−1), respectively, and mean CDs were 12 February (early) and 25 February (late). Each system had its own farmlet of eighteen paddocks and one herd that remained on the same farmlet area for the duration of the study. Stocking rate had a small effect on total herbage accumulation (11 860 kg DM ha−1 year−1), but had no effect on total herbage utilization (11 700 kg DM ha−1 year−1). Milk and milk solids ( MS; fat + protein) production per ha increased by 2580 and 196 kg ha−1 as SR increased from 2·5 to 3·3 cows ha−1. Milk production per ha and net herbage accumulation and utilization were unaffected by CD. Winter feed production was reduced as SR increased. Increased SR, associated with increased grazing severity, resulted in swards of increased leaf content and nutritive value. The results indicate that, although associated with increased milk production per ha, grazed grass utilization and improved sward nutritive value, the potential benefits of increased SR on Irish dairy farms can only be realized if the average level of herbage production and utilization is increased. [ABSTRACT FROM AUTHOR]

Background Mohs micrographic surgery ( MMS) is the gold-standard treatment for high-risk basal cell carcinomas and a variety of other cutaneous tumours, including dermatofibromasarcoma protuberans and microcystic adnexal carcinoma. Previous large-scale case series, audits and reviews have allowed evaluation of MMS outcomes, such as BCC recurrence rates. However, to date there has been no systematic UK MMS audit, and certain important aspects of care, such as postoperative functional outcomes, have not yet been subject to scrutiny. Aims To review audit data from our centre, and from this to develop a minimum dataset and audit standards for UK MMS centres, on behalf of the British Society of Dermatological Surgery ( BSDS). Methods An MMS database was developed locally and modified in response to repeated audit cycles since the introduction of the MMS service. A minimum dataset was developed using this experience. Results In our department, primary BCC recurrence rates are reassuringly low at 0.3%, at both 2 and 5 years. Histopathological discordance is < 2%, and aesthetic and functional outcomes at 3 months are good. Conclusions The collation of audit data has been simplified by use of the minimum dataset, which we propose for all UK MMS centres, on behalf of the BSDS. [ABSTRACT FROM AUTHOR]

Plasmacytoid dendritic cells (pDCs) fulfil multiple roles in immunity, and can secrete large amounts of interferon (IFN)-α. However, the available evidence suggests that they may actually counteract efficient antitumour immunity. Thus in melanoma, pDCs are abundant, but they are anergic and deficient in IFN-α secretion. pDC anergy is thought to be caused by immunosuppressive factors secreted by melanoma cells. One factor strongly expressed by melanoma is Wnt5a, which is implicated in cancer tissue invasion. In this paper, we show that Wnt5a is able to block the upregulation of the activation markers CD80 and CD86 on naive human pDCs stimulated by CpG oligodeoxynucleotide, and CpG-triggered secretion of IFN-α by pDCs. Our results suggest that Wnt5a may not only initiate cancer invasion, but could also regulate activation of pDC. These data provide a clear rationale to investigate a role for Wnt5a in immune regulation. [ABSTRACT FROM AUTHOR]

Background:Novel prognostic biomarkers and therapeutic strategies are urgently required for malignant melanoma. Ecto-5-prime-nucleotidase (NT5E; CD73) overexpression has been reported in several human cancers. The mechanism(s) underlying deregulated expression and the clinical consequences of changes in expression are not known.Methods:We used RT-PCR, qPCR, methylation-specific PCR and pyrosequencing to analyse expression and regulation of NT5E in malignant melanoma cell lines and primary and metastatic melanomas.Results:NT5E is subject to epigenetic regulation in melanoma. NT5E mRNA is downregulated by methylation-dependent transcriptional silencing in the melanoma cell lines SKMel2, SKMel23, WM35, Mel501, Mel505 and C81-61 and expression is reactivated by azacytidine. In contrast, the CpG island is unmethylated and the gene expressed in cultured normal melanocytes. In clinical cases of melanoma, methylation in the NT5E CpG island occurs in both primary and metastatic melanomas and correlates with transcriptional downregulation of NT5E mRNA. Relapse with metastatic disease, particularly to the visceral sites and brain, is more common in primary melanomas lacking NT5E methylation. Primary melanomas with methylation in NT5E show limited metastatic potential or more commonly metastasise predominantly to nodal sites rather than viscera and brain (P=0.01).Conclusion:Deregulation of NT5E expression in melanoma occurs via epigenetic changes in the NT5E CpG island. Confirmation of our results in larger clinical series would support the candidacy of NT5E as a clinical biomarker in melanoma, which could be applied in both primary and relapsed disease. Inhibition of NT5E may have therapeutic potential in melanoma, particularly in patients with more aggressive disease metastatic to viscera or the brain. [ABSTRACT FROM AUTHOR]

Proteins containing a caveolin-binding domain (CBD), such as the Rho-GTPases, can interact with caveolin-1 (Cav1) through its caveolin scaffold domain. Rho-GTPases are important regulators of p130Cas, which is crucial for both normal cell migration and Src kinase-mediated metastasis of cancer cells. However, although Rho-GTPases (particularly RhoC) and Cav1 have been linked to cancer progression and metastasis, the underlying molecular mechanisms are largely unknown. To investigate the function of Cav1-Rho-GTPase interaction in metastasis, we disrupted Cav1-Rho-GTPase binding in melanoma and mammary epithelial tumor cells by overexpressing CBD, and examined the loss-of-function of RhoC in metastatic cancer cells. Cancer cells overexpressing CBD or lacking RhoC had reduced p130Cas phosphorylation and Rac1 activation, resulting in an inhibition of migration and invasion in vitro. The activity of Src and the activation of its downstream targets FAK, Pyk2, Ras and extracellular signal-regulated kinase (Erk)1/2 were also impaired. A reduction in α5-integrin expression, which is required for binding to fibronectin and thus cell migration and survival, was observed in CBD-expressing cells and cells lacking RhoC. As a result of these defects, CBD-expressing melanoma cells had a reduced ability to metastasize in recipient mice, and impaired extravasation and survival in secondary sites in chicken embryos. Our data indicate that interaction between Cav1 and Rho-GTPases (most likely RhoC but not RhoA) promotes metastasis by stimulating α5-integrin expression and regulating the Src-dependent activation of p130Cas/Rac1, FAK/Pyk2 and Ras/Erk1/2 signaling cascades. [ABSTRACT FROM AUTHOR]

Objectives The aim of the study was to determine total and unbound lopinavir (LPV) plasma concentrations in HIV-infected pregnant women receiving lopinavir/ritonavir (LPV/r tablet) undergoing therapeutic drug monitoring (TDM) during pregnancy and postpartum. Methods Women were enrolled in the study who were receiving the LPV/r tablet as part of their routine prenatal care. Demographic and clinical data were collected and LPV plasma (total) and ultrafiltrate (unbound) concentrations were determined in the first, second and third trimesters using highperformance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Postpartum sampling was performed where applicable. Antepartum and postpartum trough concentrations (Ctrough) were compared independently [using analysis of variance (ANOVA)] and on a longitudinal basis (using a paired t-test). Results Forty-six women were enrolled in the study (38 Black African). Forty women initiated LPV/r treatment in pregnancy. Median (range) gestation at initiation was 25 (15-36) weeks and median (range) baseline CD4 count and viral load were 346 (14-836) cells/μL and 8724 (<50-267408) HIV-1 RNA copies/mL, respectively. Forty women (87%) had LPV concentrations above the accepted minimum effective concentration for wild-type virus (MEC; 1000 ng/mL). Geometric mean (95% confidence interval [CI]) total LPV concentrations in the first/second [3525 (2823-4227) ng/mL; n=16] and third [3346 (2813-3880) ng/mL; n=43] trimesters were significantly lower relative to postpartum [5136 (3693-6579) ng/mL; n=12] (P=0.006). In a paired analysis (n=512), LPV concentrations were reduced in the third trimester [3657 (2851-4463) ng/mL] vs. postpartum (P=0.021). No significant differences were observed in the LPV fraction unbound (fu%). Conclusions The above target concentrations achieved in the majority of women and similarities in the fu% suggest standard dosing of the LPV/r tablet is appropriate during pregnancy. However, reduced LPV concentrations in the second/third trimesters and potentially compromised adherence highlight the need for TDM-guided dose adjustment in certain cases. [ABSTRACT FROM AUTHOR]

Background The calcipotriol/betamethasone dipropionate two-compound product Dovobet®/Daivobet®/Taclonex®(LEO Pharma A/S, Ballerup, Denmark) has been shown to be safe and effective in the treatment of psoriasis for up to 8 weeks. As psoriasis is a chronic disease, long-term treatment may be required, so there is a need to investigate the safety of its use over a longer period of time. Objectives To investigate the safety of two treatment regimens involving use of the two-compound product over 52 weeks in the treatment of patients with psoriasis. Methods Patients ( n = 634) were randomized double-blind to treatment with: (i) 52 weeks of the two-compound product (two-compound group); (ii) 52 weeks of alternating 4-week periods of the two-compound product and calcipotriol (alternating group); or (iii) 4 weeks of the two-compound product followed by 48 weeks of calcipotriol (calcipotriol group). Treatments in all groups were used once daily when required. Results Adverse drug reactions (ADRs) occurred in 45 (21·7%) patients in the two-compound group, 63 (29·6%) in the alternating group and 78 (37·9%) in the calcipotriol group. The odds ratio for an ADR in the two-compound group relative to the calcipotriol group was 0·46 (95% confidence interval 0·30–0·70; P < 0·001). ADRs of concern associated with long-term topical corticosteroid use occurred in 10 (4·8%) patients in the two-compound group, six (2·8%) in the alternating group and six (2·9%) in the calcipotriol group; those with the highest incidence were skin atrophy, occurring in four (1·9%), one (0·5%) and two (1·0%) patients, respectively, and folliculitis, in three (1·4%), one (0·5%) and no patients, respectively. Conclusions Treatment with the two-compound product for up to 52 weeks appears to be safe and well tolerated whether used on its own or alternating every 4 weeks with calcipotriol treatment. [ABSTRACT FROM AUTHOR]

.ASA-A two-compound ointment containing calcipotriol 50 µg g−1 and betamethasone dipropionate 0·5 mg g−1 has recently been shown to be an effective treatment for psoriasis. This study was designed to investigate efficacy and safety of different treatment regimens with the two-compound product (Daivobet®/Dovobet®; LEO Pharma, Ballerup, Denmark) and calcipotriol 50 µg g−1 ointment (Daivonex®/Dovonex®; LEO Pharma). In total, 972 patients with psoriasis vulgaris were randomized to one of three treatment regimens: group 1, the two-compound product once daily for 8 weeks followed by calcipotriol ointment once daily for 4 weeks; group 2, the two-compound product once daily for 4 weeks followed by 8 weeks of treatment with calcipotriol ointment once daily on weekdays and the two-compound product once daily at weekends; and group 3, calcipotriol ointment twice daily for 12 weeks. The efficacy was evaluated by Psoriasis Area and Severity Index (PASI) and investigators' global assessments of disease severity. The primary response criteria were percentage reduction in PASI and proportion of patients with absent/very mild disease according to the investigators' global assessments after 8 weeks of treatment. The mean reduction in PASI from baseline to the end of 8 weeks of treatment was 73·3% for group 1, 68·2% for group 2 and 64·1% for group 3. The proportion of patients with absent/very mild disease at the end of 8 weeks of treatment was 55·3% for group 1, 47·7% for group 2 and 40·7% for group 3. For both primary response criteria, group 1 was statistically superior to group 3 ( P < 0·001), whereas group 2 did not differ significantly from group 3. The difference between group 1 and group 2 was statistically significant with regard to PASI but not regarding the proportion of patients with absent/very mild disease. Patients receiving initial therapy with the two-compound product achieved the fastest treatment response, and the maximum treatment effect for these patients was seen after 5 weeks. This effect was maintained with continued treatment with the two-compound product for up to 8 weeks. After 12 weeks of treatment, no significant differences were seen between the three groups with regard to reduction in PASI, whereas the proportion of patients with absent/very mild disease in group 2 was superior to that in group 3. Patients receiving therapy with the two-compound product experienced fewer lesional/perilesional adverse drug reactions than the calcipotriol-treated patients ( P < 0·001): 10·9% in group 1, 11·5% in group 2 and 22·3% in group 3. Two different short-term treatment regimens employing a recently developed two-compound product (calcipotriol/betamethasone dipropionate) provided rapid and marked clinical efficacy and were shown to be safe therapies for psoriasis vulgaris. [ABSTRACT FROM AUTHOR]

This manuscript describes the Siblings Coping Together program, a group intervention that addresses emotional and behavior problems of siblings of children with cancer and presents preliminary findings. The program is manualized and consists of 8 weekly 2-hr sessions. Each session focuses on a predetermined theme with specific goals and activities. Seventeen siblings participated in a pre- and post group pilot evaluation. Data were collected from children and parents using standardized instruments, a satisfaction questionnaire, and a group process log completed by therapists. Siblings' reports suggest a trend in the reduction of anxiety and depressive symptoms post intervention, siblings and parents reported satisfaction with the intervention group, and the results of the analysis of the group log illustrated trends in group development. This preliminary study exemplifies key group intervention components for this population and supports the need for further systematic evaluation of the intervention program. [ABSTRACT FROM AUTHOR]

The Millon Clinical Multiaxial Inventory (MCMI) was administered to 144 men and 86 women within 1 month of admission to methadone maintenance treatment and was readministered 18 months following admission. Based on prior research, we hypothesized there would be significant decreases on scales measuring affective disturbance, anxiety, and social isolation and little change in scales measuring antisocial and narcissistic traits. In addition, it was hypothesized that changes on the MCMI would be related to retention in treatment and illicit drug use during the interim between initial assessment and follow-up. Data were analyzed using a multivariate analysis of variance (MANOVA) for repeated measures. There was an overall decrease in MCMI scores, indicating less psychopathology between initial assessment and follow-up. MCMI scales did not change as a function of retention status, but decreases in MCMI scale scores were greater for subjects who were light drug users in the 6 months prior to the follow-up compared to heavy users. Inspection of individual MCMI scales supported our hypothesis; there were decreases on scales measuring affective disturbance, anxiety, and social isolation, but not on scales measuring antisocial and narcissistic traits. [ABSTRACT FROM AUTHOR]

An 18-year-old woman presented with severe features of seborrhoeic dermatitis involving her scalp. Subsequently, the toe webs and intertriginous areas became affected by an erythematous, slightly scaly and weepy rash. The groin area was most severely affected, and complicated by intermittent infections with staphylococci and herpes simplex. The patient admitted to smoking heroin and was subsequently enrolled in a methadone programme. A biopsy from the groin area showed a combination of parakeratosis and keratinocyte vacuolar changes, supporting a diagnosis of necrolytic migratory erythema (NME). On completion of methadadone withdrawal, the rash cleared. The rash returned upon recommencing methadone. NME consists of an irregular annular eruption with an erythematous crusted edge. It is often mistaken for intertrigo or seborrhoeic dermatitis. In this patient, a direct effect of heroin and methadone on the epidermal metabolism might be speculated. There could be a variant of the opiate recepter, which is especially sensitive to the effects of opiates. This is the second case occurring in association with opiate dependency and the first case where the patient was rechallenged, although the precise role of the opiates in the aetiology remains somewhat speculative. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article about a randomized study of minimal curettage followed by topical photodynamic therapy compared with surgical excision for low-risk nodular basal cell carcinoma, which appeared within the issue.

Summary: 特应性皮炎 (AD) 通常简称为湿疹,是一种广泛存在的疾病,影响全球 15‐25% 的儿童和 4‐7% 的成人。AD 可引起皮肤干燥和瘙痒,对许多人来说是一种终生困扰。 AD 差异很大,在许多患者中在轻度和重度之间波动。每日两次大量使用保湿剂(称为"润肤剂")以及涂抹在发炎皮肤区域的含类固醇乳膏有助于治疗 AD。 因此,指南建议每周使用一品脱大小装的润肤剂。然而,目前尚不清楚患者实际使用了多少保湿剂和类固醇乳膏。 为了找出这一点,来自英国的研究人员分析了电子药房配药记录,上面显示了患者正在使用多少药物。 最重要的发现如下:首先,事实上大多数患者只使用极少量的保湿剂——少于一管标准牙膏(17 克)的三分之一,其用量应该覆盖他们的整个身体,每天两次。其次,使用类固醇乳膏总体上不会超过指南建议,这是令人欣慰的。 第三,使用类固醇乳膏和治疗抑郁症之间有很强的相关性。因此,在需要大量类固醇乳膏(每月 50 克或更多)的患者中,需要定期抗抑郁治疗的患者数量几乎是使用较少量类固醇乳膏患者中需要定期抗抑郁治疗的患者数量的两倍。这一发现证实了之前关于目前患有抑郁症和更严重 AD 之间联系的提示。 重要的是,研究结果强调了增加使用保湿剂的迫切需求,精神健康对 AD 严重程度的影响可能比想象的更严重。 本摘要涉及研究:特应性皮炎局部治疗的定量分析:润肤剂的使用率出乎意料地低,局部使用皮质类固醇与抑郁症和并发哮喘均有很强的相关性 [ABSTRACT FROM AUTHOR]

Summary: Atopic dermatitis (AD), often known simply as eczema, is a widespread condition, affecting between 15‐25% of children and between 4‐7% of adults worldwide. AD causes dry and itchy skin, and for many is a life‐long affliction. AD varies enormously, fluctuating between mild and severe in many patients. Twice daily and generous application of moisturisers (called "emollients"), as well as steroid‐containing creams applied to inflamed skin areas, can help to treat AD. For this reason, guidelines recommend the use of a pint‐sized tub of emollients per week. However, it is unknown how much moisturiser and steroid creams patients actually use. In order to find this out, researchers from the U.K. analysed electronic pharmacy dispensing records, which show how much of a medication patients are using. The most important findings were as follows: First, most patients in fact only use tiny amounts of moisturisers ‐ less than a third of a standard toothpaste tube (17 gram), for what should cover their entire body twice daily. Second, the use of steroid creams does not, on the whole, exceed guideline recommendations, which is reassuring. Third, there is a strong association between the use of steroid creams and treatment for depression. Thus, the number of patients requiring regular antidepressant treatment is almost double among patients requiring high amounts of steroid creams (50 gram or more per month) compared to those using lower amounts. This finding confirms previous suggestions of a link between currently having depression and more severe AD. Importantly, the findings highlight an urgent need for increased use of moisturisers, and that mental health may impact more heavily than thought on AD severity. This is a summary of the study: Quantitative analysis of topical treatments in atopic dermatitis: unexpectedly low use of emollients and strong correlation of topical corticosteroid use both with depression and concurrent asthma [ABSTRACT FROM AUTHOR]

Summary: 银屑病是一种极为常见的疾病, 影响全世界大约 2% 人口和英国约 150 万人口。很多患者终生受到影响。银屑病通常可通过乳膏治疗。但是, 当这种治疗效果不足时, 患者可通过称为"窄波‐UVB"的特殊滤过紫外光治疗。这种治疗极为有效 (有效率 3/4) 安全, 且不需要血液检查。但是, 在很多地区并不易于获得。造成这种情况的一个原因是, 它被认为昂贵, 因为患者需要每周进行 3 次治疗, 每次数分钟, 持续数周, 且由工作人员给予治疗。在这项研究中, 作者们提取英国一家大型供应商 NHS Tayside 在 6 年中为此治疗发生的所有治疗费用。包括所有间接费用 (如养恤基金、房地产等), NHS Tayside 每人每次完整治疗平均仅花费 257 英镑。这一结果显示, 向更多患者提供此治疗极其物有所值, 并可能在很多患者中避免或延迟使用免疫抑制药物。 Linked Article: Boswell et al. Br J Dermatol 2018; 179:1148–1156 [ABSTRACT FROM AUTHOR]

Summary: Psoriasis is a very common disease, affecting around 2% of people worldwide and 1.5 million in the UK. Many patients are affected throughout their lives. Psoriasis can often be treated with creams. However, when this is not enough patients can be treated by specially filtered ultraviolet light called "narrowband‐UVB". This treatment is very effective in 3 out of 4 people, safe, and does not require blood testing. However, in many regions it is not readily available. One reason for this is that it is regarded as expensive since patients have to attend 3 times per week for a few minutes for several weeks, and staff administer the treatment. In this study, the authors extracted all the treatment cost that one large provider in the UK, NHS Tayside, has incurred over six years for this treatment. Including even all indirect costs such as pension contribution, estate etc., NHS Tayside spent an average of only £257 per person for a complete treatment. This result suggests that offering this treatment to more patients would be very cost effective and might avoid or delay the need to use immunosuppressive drugs in many patients. Linked Article: Boswell et al. Br J Dermatol 2018; 179:1148–1156 [ABSTRACT FROM AUTHOR]

Objectives Ivacaftor produces significant benefit in patients with cystic fibrosis (CF) with the G551D mutation. Recent data have supported improved insulin secretion profile and reversal of CF related diabetes (CFRD) in patients treated with ivacaftor. Significant weight gain has been demonstrated with ivacaftor, thus raising the potential for development of dyslipidaemia in a cohort traditionally treated with a high fat diet. Methods 24 Adult patients with the G551D mutation had Oral Glucose Tolerance Test (OGTT), Fasting lipid profile and HbA1C measured before and after commencing ivacaftor therapy. 6 patients had pre-existing CFRD and Insulin requirements were analysed in this cohort before and after ivacaftor. Data was analysed using Wilcoxon signed-rank test. Results No significant change was observed in fasting glucose, 2 hour post prandial glucose, or HbA1C after commencement of ivacaftor. Significant median increase in total fasting cholesterol (0.2 mmol/L, P = 0.025) and HDL (0.16 mmol/L, P = 0.03) were observed after commencement of treatment. There was no significant change in LDL or Triglycerides. In the 6 patients with CFRD no significant change in either total insulin requirements or units of insulin per kilogram of weight were observed. Conclusion In a large single centre cohort with the G551D mutation we report no significant change in OGTT, HbA1c or insulin requirements after ivacaftor. While a significant increase in Fasting cholesterol was observed, median values were within normal limits. Changes in lipid profile may reflect the impact of adhering to a high fat diet as a consequence of therapy and will required long-term follow up. [ABSTRACT FROM AUTHOR]

Objective CF is associated with altered digestive function and thus nutrient availability for gut microbes in addition to altered gut microbiota, compared with healthy controls. Equally intensive antibiotic and nutritional therapy may further compound this. We present results from the largest CF gut microbiota study to date. Methods The gut microbiota of 43 stable adults with CF was compared to 69 age-matched controls. DNA was extracted from faecal samples and the V4 region of the 16S rRNA gene was sequenced using 454-pyrosequencing. Results were correlated with baseline %FEV 1 results and to total courses of IVs in the previous 12 months. Results The gut microbiota diversity of patients with CF was significantly reduced compared to controls (p<0.05 for all a diversity tests). Significantly increased proportions of Firmicutes (p = 0.029) and decreased Bacteroidetes (p<0.001) occurred in those with CF compared to controls. There were significant reductions in proportions of bacteria associated with gut health in those with CF, including decreased Faecalibacterium, Roseburia and Bifidobacterium (p<0.001). A negative correlation between the number of IV courses and gut diversity [Simpson's diversity index: correlation coefficient (r) = –0.383, p = 0.0111] and a positive correlation between FEV 1 and gut diversity (Simpson's diversity index: r = 0.47, p = 0.0015) was found in those with CF. Conclusion This study highlights that patients with CF have an altered gut microbiota which correlates with clinical outcomes. Further longitudinal studies will enable us to interrogate the causality of such microbiota alterations and determine the potential role of probiotics in CF therapy. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented which discusses the examination audit of the techniques and procedures of Mohs micrographic surgery (MMS).