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Background: Incidence of non-melanoma skin cancers (NMSCs) is increasing and can significantly impact on quality of life (QOL), yet there are few studies evaluating patient-reported outcome measures (PROMs) in NMSC populations. We undertook a prospective feasibility study to evaluate a skin cancer-specific PROM, the Skin Cancer Quality of Life Impact Tool (SCQOLIT), in patients with a new diagnosis of NMSC., Objectives: (i) To establish acceptability of SCQOLIT in dermatology clinics, (ii) a descriptive analysis of SCQOLIT scores in NMSC., Methods: Patients with histologically confirmed NMSC completed SCQOLIT, EQ-5D and a transition item. Questionnaires were completed at baseline and 3 months for group 1 ('low-risk' NMSC) and group 2 ('high-risk' NMSC) with additional questionnaires at 6-9 months for group 2. Patients participated in structured interviews. Clinician experience was captured through staff evaluation forms and a focus group. Acceptability and psychometric properties of SCQOLIT were assessed., Results: Overall, 318 patients consented to participate. Mean SCQOLIT score at baseline was 5.33, with 2.6% of patients scoring ≥20. No ceiling effects were observed, whilst 13.9% scored 0. Validity was demonstrated against EQ-5D. Cronbach's alpha 0.84 demonstrated internal consistency. Thirteen patients were interviewed and thought SCQOLIT was comprehensive, captured impact on health-related QOL and helped express their needs to clinicians. Most clinicians found SCQOLIT 'very useful' or 'useful to some extent' in facilitating discussions., Conclusions: This feasibility study demonstrates that SCQOLIT is acceptable to patients and staff in dermatology skin cancer clinics. The psychometric properties of SCQOLIT confirm its utility in NMSC populations., (© 2019 European Academy of Dermatology and Venereology.)

Dermatofibrosarcoma protuberans is a rare soft tissue tumour with a very low (p < 0.5%) rate of metastasis. Rates of re-excision and recurrence were determined using data from the Netherlands Cancer Registry between 1989 and 2016. Of the 1,890 instances of dermatofibrosarcoma protuberans included, 87% were treated with excision, 4% with Mohs micrographic surgery, and 9% otherwise or unknown. Linked pathology data were retrieved for 1,677 patients. Half of all excisions (847/1,644) were incomplete and 29% (192/622) of all re-excisions were incomplete. The cumulative incidence of a recurrence was 7% (95% confidence interval (95% CI) 6-8) during a median follow-up of 11 years (interquartile range (IQR) 6-17). After Mohs micrographic surgery (n = 34), there were no recurrences during a median follow-up of 4 years (IQR 3-6). Due to the high rate of incomplete excisions and recurrences after excision, this study supports the European guideline, which recommends treating dermatofibrosarcoma protuberans with Mohs micrographic surgery in order to decrease the rate of recurrence.

Background: Survival in mycosis fungoides (MF) is varied and may be poor. The PROCLIPI (PROspective Cutaneous Lymphoma International Prognostic Index) study is a web-based data collection system for early-stage MF with legal data-sharing agreements permitting international collaboration in a rare cancer with complex pathology. Clinicopathological data must be 100% complete and in-built intelligence in the database system ensures accurate staging., Objectives: To develop a prognostic index for MF., Methods: Predefined datasets for clinical, haematological, radiological, immunohistochemical, genotypic, treatment and quality of life are collected at first diagnosis of MF and annually to test against survival. Biobanked tissue samples are recorded within a Federated Biobank for translational studies., Results: In total, 430 patients were enrolled from 29 centres in 15 countries spanning five continents. Altogether, 348 were confirmed as having early-stage MF at central review. The majority had classical MF (81·6%) with a CD4 phenotype (88·2%). Folliculotropic MF was diagnosed in 17·8%. Most presented with stage I (IA: 49·4%; IB: 42·8%), but 7·8% presented with enlarged lymph nodes (stage IIA). A diagnostic delay between first symptom development and initial diagnosis was frequent [85·6%; median delay 36 months (interquartile range 12-90)]. This highlights the difficulties in accurate diagnosis, which includes lack of a singular diagnostic test for MF., Conclusions: This confirmed early-stage MF cohort is being followed-up to identify prognostic factors, which may allow better management and improve survival by identifying patients at risk of disease progression. This study design is a useful model for collaboration in other rare diseases, especially where pathological diagnosis can be complex., (© 2018 British Association of Dermatologists.)

Appropriate post-translational processing of collagen requires prolyl hydroxylation, catalyzed by collagen prolyl 3-hydroxylase and collagen prolyl 4-hydroxylase, and is essential for normal cell function. Here we have investigated the expression, transcriptional regulation, and function of the collagen prolyl 3-hydroxylase and collagen prolyl 4-hydroxylase families in melanoma. We show that the collagen prolyl 3-hydroxylase family exemplified by Leprel1 and Leprel2 is subject to methylation-dependent transcriptional silencing in primary and metastatic melanoma consistent with a tumor suppressor function. In contrast, although there is transcriptional silencing of P4HA3 in a subset of melanomas, the collagen prolyl 4-hydroxylase family members P4HA1, P4HA2, and P4HA3 are often overexpressed in melanoma, expression being prognostic of worse clinical outcomes. Consistent with tumor suppressor function, ectopic expression of Leprel1 and Leprel2 inhibits melanoma proliferation, whereas P4HA2 and P4HA3 increase proliferation, and particularly invasiveness, of melanoma cells. Pharmacological inhibition with multiple selective collagen prolyl 4-hydroxylase inhibitors reduces proliferation and inhibits invasiveness of melanoma cells. Together, our data identify the collagen prolyl 3-hydroxylase and collagen prolyl 4-hydroxylase families as potentially important regulators of melanoma growth and invasiveness and suggest that selective inhibition of collagen prolyl 4-hydroxylase is an attractive strategy to reduce the invasive properties of melanoma cells., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The treatment of actinic keratosis (AK) is a potentially effective strategy for the prevention of cutaneous squamous cell carcinoma (cSCC). However, the patient perspective on potential benefits of AK treatment in terms of skin cancer reduction has received little attention to date., Objectives: (i) To investigate patient preferences for topical treatments for AK using a discrete-choice experiment (DCE); (ii) to evaluate patient willingness to trade between clinical benefit and medical burden., Methods: The DCE was conducted as part of a study to establish the feasibility of a phase III randomized controlled trial evaluating the prevention of cSCC using currently available topical interventions. Preferences were elicited by asking patients to make a series of choices between treatment alternatives with different hypothetical combinations of attribute levels. Willingness to trade between treatment attributes was estimated using a flexible-choice model that allows for the heterogeneity of patient preferences., Results: A total of 109 patients with AK completed the DCE. The majority of patients who expressed valid preferences were willing to accept some reduction in both prophylactic and cosmetic efficacy to reduce the burden of the treatment regimen, the severity of skin reaction and other adverse effects. Patients may reject treatment if the perceived therapeutic benefit is outweighed by the subjective burden of treatment., Conclusions: Evidence of significant variation in the perceived utility of treatments across patients highlights the importance of taking individual patient preferences into account to improve AK treatment acceptability and adherence., (© 2018 British Association of Dermatologists.)

Despite emergence of new systemic therapies, metastatic melanoma remains a challenging and often fatal form of skin cancer. The renin-angiotensin system (RAS) is a major physiological regulatory pathway controlling salt-water equilibrium, intravascular volume and blood pressure. Biological effects of the RAS are mediated by the vasoactive hormone angiotensin II (AngII) via two receptor subtypes, AT1R (encoded by AGTR1) and AT2R (encoded by AGTR2). We report decreasing expression and increasing CpG island methylation of AGTR1 in metastatic versus primary melanoma and detection in serum of methylated genomic DNA from the AGTR1 CpG island in metastatic melanoma implying that AGTR1 encodes a tumour suppressor function in melanoma. Consistent with this hypothesis, antagonism of AT1R using losartan or shRNA-mediated knockdown in melanoma cell lines expressing AGTR1 resulted in acquisition of the ability to proliferate in serum-free conditions. Conversely, ectopic expression of AGTR1 in cell lines lacking endogenous expression inhibits proliferation irrespective of the presence of AngII implying a ligand-independent suppressor function for AT1R. Treatment of melanoma cell lines expressing endogenous AT2R with either AngII or the AT2R-selective agonist Y6AII induces proliferation in serum-free conditions whereas the AT2R-specific antagonists PD123319 and EMA401 inhibit melanoma growth and angiogenesis and potentiate inhibitors of BRAF and MEK in cells with BRAF V600 mutations. Our results demonstrate that the RAS has both oncogenic and tumour suppressor functions in melanoma. Pharmacological inhibition of AT2R may provide therapeutic opportunities in melanomas expressing this receptor and AGTR1 CpG island methylation in serum may serve as a novel biomarker of metastatic melanoma.

The lattice Boltzmann method has become one of the standard techniques for simulating a wide range of fluid flows. However, the intrinsic coupling of momentum and space discretization restricts the traditional lattice Boltzmann method to regular lattices. Alternative off-lattice Boltzmann schemes exist for both single- and multiphase flows that decouple the velocity discretization from the underlying spatial grid. The current study extends the applicability of these off-lattice methods by introducing a finite element formulation that enables simulating contact line dynamics for partially wetting fluids. This work exemplifies the implementation of the scheme and furthermore presents benchmark experiments that show the scheme reduces spurious currents at the liquid-vapor interface by at least two orders of magnitude compared to a nodal implementation and allows for predicting the equilibrium states accurately in the range of moderate contact angles.

Background: Volatile organic compounds (VOCs) are continuously released by the body during normal metabolic processes, but their profiles change in the presence of cancer. Robust evidence that invasive melanoma in vivo emits a characteristic VOC signature is lacking., Objectives: To conduct a canine olfactory, proof-of-principle study to investigate whether VOCs from invasive melanoma are distinguishable from those of basal cell carcinoma (BCC), benign naevi and healthy skin in vivo., Methods: After a 13-month training period, the dog's ability to discriminate melanoma was evaluated in 20 double-blind tests, each requiring selection of one melanoma sample from nine controls (three each of BCC, naevi and healthy skin; all samples new to the dog)., Results: The dog correctly selected the melanoma sample on nine (45%) occasions (95% confidence interval 0·23-0·68) vs. 10% expected by chance alone. A one-sided exact binomial test gave a P-value of < 0·01, supporting the hypothesis that samples were not chosen at random but that some degree of VOC signal from the melanoma samples significantly increased the probability of their detection. Use of a discrete-choice model confirmed melanoma as the most influential of the recorded medical/personal covariates in determining the dog's choice of sample. Accuracy rates based on familiar samples during training were not a reliable indicator of the dog's ability to distinguish melanoma, when confronted with new, unknown samples., Conclusions: Invasive melanoma in vivo releases odorous VOCs distinct from those of BCC, benign naevi and healthy skin, adding to the evidence that the volatile metabolome of melanoma contains diagnostically useful biomarkers., (© 2016 British Association of Dermatologists.)

Introduction: Vitiligo is an acquired skin disorder characterised by white (depigmented) patches in the skin, due to the loss of functioning melanocytes. The extent and distribution of vitiligo often changes during the course of a person's lifetime and its progression is unpredictable., Methods and Outcomes: We conducted a systematic review and aimed to answer the following clinical question: What are the effects of surgical interventions for vitiligo in adults and in children? We searched: Medline, Embase, The Cochrane Library, and other important databases up to April 2014 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA)., Results: We found four studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions., Conclusions: In this systematic review we present information relating to the effectiveness and safety of the following interventions: blister grafts, cultured cellular transplantation, non-cultured cellular transplantation, punch/mini grafts, and split thickness skin grafts.

As an alternative to state-of-the-art laser frequency stabilization using ultrastable cavities, it has been proposed to exploit the nonlinear effects from coupling of atoms with a narrow transition to an optical cavity. Here, we have constructed such a system and observed nonlinear phase shifts of a narrow optical line by a strong coupling of a sample of strontium-88 atoms to an optical cavity. The sample temperature of a few mK provides a domain where the Doppler energy scale is several orders of magnitude larger than the narrow linewidth of the optical transition. This makes the system sensitive to velocity dependent multiphoton scattering events (Dopplerons) that affect the cavity field transmission and phase. By varying the number of atoms and the intracavity power, we systematically study this nonlinear phase signature which displays roughly the same features as for much lower temperature samples. This demonstration in a relatively simple system opens new possibilities for alternative routes to laser stabilization at the sub-100 mHz level and superradiant laser sources involving narrow-line atoms. The understanding of relevant motional effects obtained here has direct implications for other atomic clocks when used in relation to ultranarrow clock transitions.

Background: Burn injuries impose a considerable burden on healthcare systems in Iran. It is among the top ten causes of mortality and a main cause of disability., Objectives: This study aimed to examine factors influencing mortality in burn patients admitted to the main educational tertiary referral hospital in Kermanshah., Patients and Methods: All patients admitted to the Imam Khomeini Hospital (from March 2011 to March 2012), due to thermal burn injuries were included in the study. We applied multiple logistic regressions to identify risk and protective factors of mortality. Also we calculated lethal area fifty percent (LA50), as an aggregate index for hospital quality., Results: During the study period, 540 burn patients were admitted. Male to female ratio was 1.12:1. Twenty three percent of the patients were less than 15 years-old. Median of age was 25 years (Inter Quartile Range, 16 - 37). Overall, probability of death was 25.8%. Lethal area fifty percent (LA50) was 50.82 (CI 95%: 47.76 - 54.48). In the final model, after adjustment of sex, age, total body surface area (TBSA), cause of burn and it's severity, female gender (P < 0.05), age ≥ 60 years (in comparison with age less than 15 years, P < 0.05) and larger burn size (P < 0.0001) were identified as the main risk factors of death in these patients., Conclusions: Findings showed that the main risk factors of death were female gender, burn size and old age. Directing more attention to these vulnerable patients is required to reduce mortality and improve patient survival.

Background: Burns are among the most common injuries affecting a great number of people worldwide annually. In Iran, especially in its western region and in Kermanshah province, burns have a relatively high incidence. The present study was aimed at investigating epidemiological characteristics in Western Iran., Methods: Within a cross-sectional study, the data on all patients attending the Burns Center at Imam Khomeini Hospital (Kermanshah, Iran) during 2010-2011 and 2011-2012 (24 months) were collected. Then, age, gender, cause of burns, total body surface area, and time of the occurrence were extracted from the hospital records. The data were analyzed using the SPSS statistical package (Version 19, for Windows). We used chi-squared test when we compared the categorical responses between two or more groups. For comparing means between two groups we used t-test. In addition, trends were investigated using linear regression., Results: Overall 13,248 people were referred to the Burns Center at Imam Khomeini Hospital (Kermanshah, Iran) during the period of study, including 328 cases of self-immolation. The mean age of the patients was 27±19 years and 29±13 years for unintentional burns and self-immolation respectively. Out of the total number of unintentional cases, 6,519 (50.5%) were men, while the corresponding percentage of men among the self-immolation cases was 16.6% (p less than 0.001). Trends in the number of cases were cyclic, with the highest and lowest number of burns cases being in March and May. Overall, hot liquids and flammable materials were the two most important causes of unintentional burns. However, flammable materials were the main cause of burns among self-immolation cases. During hospital admission, 168 (51%) self-immolation victims and 43 (0.33%) unintentional burn victims died., Conclusions: While major preventive measures are not adequately used in developing countries, burns and their burden can be significantly reduced by increasing public awareness and by applying simple preventive measures., (© 2014 KUMS, All rights reserved.)

Transcriptional silencing of tissue factor pathway inhibitor 2 (TFPI2) occurs in several human tumors including melanoma. We investigated methylated TFPI2 as a biomarker of metastatic melanoma using qRT-PCR to assess TFPI2 expression and pyrosequencing to analyze CpG island methylation in malignant melanoma cell lines, in benign nevi, in 112 primary and metastatic melanomas, and in serum from 6 healthy individuals and 35 patients: 20 patients with primary and 15 patients with metastatic melanoma. The TFPI2 CpG island is unmethylated in nevi but methylation is associated with metastatic melanoma. Circulating methylated TFPI2 DNA is undetectable in sera from healthy individuals and detectable in sera from patients with primary and metastatic melanomas, but the presence of methylated TFPI2 DNA in serum is strongly associated with metastatic disease (P<0.01). Detection of TFPI2-methylated DNA in the serum of patients with resected melanoma is a sensitive and specific biomarker of metastatic melanoma. Confirmation of our results in independent patient cohorts would encourage prospective evaluation as a biomarker of disease state.

Burn injuries in both developed and developing countries cause long-term disability, mortality, and socio-economic costs that are imposed on patients, families, and societies. This study was carried out to investigate the epidemiology, outcome, and cost of hospitalization of 388 burn patients admitted to the Imam Khomeini Hospital Burn Center in Kermanshah, Iran, between 21 March 2011 and 20 March 2012. The data about demographics, cause of burns, degree of burns, outcome of burns, burned body surface (BBS), length of stay (LOS), and cost of hospitalization were collected by reviewing medical records and analysed by SPSS 16. The patients' mean age was 27 years. The male/female ratio in burn patients was 1.14/1. The mean BBS was 36.06%. The mean LOS was 9.04 days. Flame (67.0%) and hot liquids (21.9%) were the major causes of burn. Burn injuries were more common in the upper limbs (81.4%), lower limbs (70.9%), and head and neck (65.2%). 11.6% of patients had all the regions involved. The fatality rate was 18.8%. The mean cost per patient was 20,463,227 Iran Rials (IRR). The cost per one percentage of burn and one day of hospitalization was 562,632 IRR and 2,263,631 IRR, respectively. The main factors relevant to death were identified including the extent of burn, gender, age, causes, and degree of burn. In addition, LOS proved to have a higher impact on costs than burn percentage.

Introduction: Vitiligo is an acquired skin disorder characterised by white (depigmented) patches in the skin, due to the loss of functioning melanocytes. The extent and distribution of vitiligo often changes during the course of a person's lifetime and its progression is unpredictable., Methods and Outcomes: We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of medical treatments, and of ultraviolet light treatments, for vitiligo in adults and in children? We searched: Medline, Embase, The Cochrane Library, and other important databases up to March 2010 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA)., Results: We found 25 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions., Conclusions: In this systematic review we present information relating to the effectiveness and safety of the following interventions: corticosteroids (oral and topical), oral levamisole, topical immunomodulators, topical vitamin D analogues, ultraviolet A plus psoralen (PUVA [oral or topical]), and ultraviolet B (narrowband).

Introduction: Vitiligo is an acquired skin disorder characterised by white (depigmented) patches in the skin, due to the loss of functioning melanocytes. The extent and distribution of vitiligo often changes during the course of a person's lifetime and its progression is unpredictable., Methods and Outcomes: We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of medical treatments, and of ultraviolet light treatments, for vitiligo in children and in adults? We searched: Medline, Embase, The Cochrane Library and other important databases up to March 2007 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA)., Results: We found 25 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions., Conclusions: In this systematic review we present information relating to the effectiveness and safety of the following interventions: corticosteroids, oral levamisole, topical immunomodulators, topical Vitamin D analogues, ultraviolet A plus psoralen (PUVA), and ultraviolet B (narrowband, and broadband).