Search

Background: Metabolic reprogramming and altered gene expression mediated by hypoxia‐inducible factors play crucial roles during tumour growth and progression. Nevertheless, studies analysing the expression of hypoxia‐inducible factor‐1α and its downstream targets in Merkel cell carcinoma (MCC) are lacking but are warranted to shed more light on MCC pathogenesis and to potentially provide new therapeutic options. Objectives: To analyse the immunohistochemical expression of hypoxia‐inducible factor‐1α (HIF‐1α), vascular endothelial growth factor‐A (referred to as VEGF throughout the manuscript), VEGF receptor‐2 (VEGFR‐2), VEGF receptor‐3 (VEGFR‐3), glucose transporter‐1 (Glut‐1), monocarboxylate transporter 4 (MCT4) and carbonic anhydrase IX (CAIX) in primary cutaneous MCC. Methods: The 16 paraffin‐embedded primary cutaneous MCCs (Merkel cell polyomavirus (McPyV) positive/negative: 11/5) were analysed by immunohistochemistry, namely HIF‐1α, VEGF, VEGFR‐2 (KDR), VEGFR‐3 (FLT4), Glut‐1, MCT4 and CAIX. An established quantification score (QS) was applied to quantitate the protein expression by considering the percentage of positive tumour cells (0: 0%; 1: up to 1%; 2: 2–10%; 3: 11–50%; 4: >50%) in relation to the staining intensity (0: negative; 1: low; 2: medium; 3: strong). Results: HIF‐1α was expressed in all MCCs and predominantly found at the invading edges of tumour margins. The HIF‐1α downstream factors Glut‐1, MCT4 and CAIX were expressed in 13 of 16 MCC (81%), 14 of 16 MCC (88%) and 16 of 16 MCC (100%), respectively. Interestingly, VEGF and VEGFR‐2 were not expressed in tumour cells, whereas VEGFR‐3 was expressed in all MCCs. HIF‐1α was expressed significantly stronger in McPyV+ tumours (QS: 10.36 ± 2.41) than in McPyV− tumours (QS: 5.40 ± 1.34; P = 0.002). Similarly, VEGFR‐3 was also expressed significantly stronger in McPyV+ tumours (QS: 10.00 ± 2.52) than in McPyV− tumours (QS: 5.40 ± 3.43, P = 0.019). Conclusions: Our data provide first evidence for a role of HIF‐1α in induced metabolic reprogramming contributing to MCC pathogenesis. The metabolic signatures of McPyV+ and McPyV− tumours seem to show relevant differences. [ABSTRACT FROM AUTHOR]

Summary: Background: The Psoriasis Area and Severity Index (PASI) represents the gold standard for psoriasis severity assessments but is limited by its subjectivity and low intra‐ and inter‐rater consistency. Objectives: To investigate the precision and reproducibility of automated, computer‐guided PASI measurements (ACPMs) in comparison with three trained physicians. Methods: This was a comparative observational study assessing ACPMs attained by automated total‐body imaging and computerized digital image analysis in a cohort of 120 patients affected by plaque psoriasis of various severities. The level of agreement between ACPMs and physicians' PASI measurements was calculated by the intraclass correlation coefficient (ICC). The reproducibility of ACPMs in comparison with physicians' PASI measurements was investigated by performing two successive 'repeat PASI calculations' in the same patients. Results: The agreement between ACPMs and physicians' PASI calculations in 120 fully evaluable patients was high (ICC 0·86, 95% confidence interval 0·80–0·90, mean absolute difference 2·5 PASI points). Repeat ACPMs to measure the reproducibility showed an excellent ICC of 0·99 (95% confidence interval 0·98–0·99) with a mean absolute difference of 0·5 PASI points. The ACPMs thus outperformed the three physicians for intrarater reliability (mean ICC 0·86). Conclusions: The results of this first clinical study investigating ACPMs in 120 patients with psoriasis indicate a similar precision and higher reproducibility in comparison with trained physicians. Limitations arise from poorly observable body sites and from patients unable to attain predefined postures during automated image acquisition. What's already known about this topic? The Psoriasis Area and Severity Index (PASI) is the standard for psoriasis severity assessments but is limited by its subjectivity and low reproducibility. What does this study add? Automated computer‐guided PASI measurements (ACPMs) agreed with the results of trained physicians and outperformed the physicians in terms of reproducibility.ACPMs provide a first step towards a higher standardization and reproducibility of PASI measurements. Linked Comment:  Garcia‐Doval and Albrecht. Br J Dermatol 2019; 180:260–261. Respond to this article [ABSTRACT FROM AUTHOR]

Background Infantile haemangiomas ( IH) are common benign tumours in infancy. Most IH resolve spontaneously, but some require treatment due to ulceration, functional impairment or cosmetic disfiguration. While systemic propranolol is effective in many cases, laser therapy may be a safe topical alternative. Objective To assess the efficacy of combined Nd: YAG/pulsed dye laser ( PDL) or PDL alone for therapy of IH. Patients and methods A total of 271 IH in 149 infants were treated with combined Nd: YAG/ PDL or PDL alone. Based on photographs before and 4-6 weeks after the last treatment, the results were evaluated independently by three physicians. Remissions were categorized as 0-25% (I), 26-50% ( II), 51-75% ( III) and 76-100% ( IV). Results In total, 472 laser treatments were performed. In 137 of 149 infants (91.9%) laser therapy was performed during a short sevoflurane mask anaesthesia, while 12 of 149 infants (8.1%) received topical anaesthetic gel. Combined Nd: YAG/ PDL was applied in 187 of 271 IH (69.0%), while PDL alone in 84 of 271 IH (31.0%). On average, 1.74 treatments per IH were necessary (Nd: YAG/ PDL: 1.95, PDL: 1.26). Moderate or strong ( III/ IV) improvement was observed in 92.4% of all IH treated. No serious adverse effects were observed. Conclusion Combined Nd: YAG/ PDL therapy is an effective and well-tolerated local treatment option for IH of any classification, in any phase of development and at any age. With regard to the systemic use of propranolol, combined Nd: YAG/ PDL therapy seems a safe and promising alternative in many cases. [ABSTRACT FROM AUTHOR]

Background The nucleotide excision repair (NER) pathway repairs UV-induced DNA lesions in an accurate fashion and prevents UV-irradiated areas of the skin from tumour formation. The XPA protein plays a major role in DNA damage demarcation as well as stabilization of other NER factors and was found to be defective in xeroderma pigmentosum (XP) complementation group A patients. Objective Characterization of four new XP-A patients. Methods Genomic and cDNA sequencing, post-UV cell survival of living cells, host-cell reactivation of patients' fibroblasts and Western blotting. Results One of the four investigated patients shows a novel mutation leading to two different truncated protein variants. Three patients contain the already described p.R228X mutation. All patient cell lines exhibit a strong UVC sensitivity and reduced NER capability. In most of the cases stable protein expression was detected. Conclusion We discovered four new XP-A patients and a novel XPA mutation resulting in two diverse patient alleles. [ABSTRACT FROM AUTHOR]

Background Cold atmospheric plasma (CAP, i.e. ionized air) is an innovating promising tool in reducing bacteria. Objective We conducted the first clinical trial with the novel PlasmaDerm® VU-2010 device to assess safety and, as secondary endpoints, efficacy and applicability of 45 s/cm2 cold atmospheric plasma as add-on therapy against chronic venous leg ulcers. Methods From April 2011 to April 2012, 14 patients were randomized to receive standardized modern wound care (n = 7) or plasma in addition to standard care (n = 7) 3× per week for 8 weeks. The ulcer size was determined weekly (Visitrak®, photodocumentation). Bacterial load (bacterial swabs, contact agar plates) and pain during and between treatments (visual analogue scales) were assessed. Patients and doctors rated the applicability of plasma (questionnaires). Results The plasma treatment was safe with 2 SAEs and 77 AEs approximately equally distributed among both groups (P = 0.77 and P = 1.0, Fisher's exact test). Two AEs probably related to plasma. Plasma treatment resulted in a significant reduction in lesional bacterial load (P = 0.04, Wilcoxon signed-rank test). A more than 50% ulcer size reduction was noted in 5/7 and 4/7 patients in the standard and plasma groups, respectively, and a greater size reduction occurred in the plasma group (plasma -5.3 cm2, standard: -3.4 cm2) (non-significant, P = 0.42, log-rank test). The only ulcer that closed after 7 weeks received plasma. Patients in the plasma group quoted less pain compared to the control group. The plasma applicability was not rated inferior to standard wound care (P = 0.94, Wilcoxon-Mann-Whitney test). Physicians would recommend (P = 0.06, Wilcoxon-Mann-Whitney test) or repeat (P = 0.08, Wilcoxon-Mann-Whitney test) plasma treatment by trend. Conclusion Cold atmospheric plasma displays favourable antibacterial effects. We demonstrated that plasma treatment with the PlasmaDerm® VU-2010 device is safe and effective in patients with chronic venous leg ulcers. Thus, larger controlled trials and the development of devices with larger application surfaces are warranted. [ABSTRACT FROM AUTHOR]

Background Factors associated with early vs. late diagnosis of cutaneous melanoma remain poorly understood. Objective To identify factors with a significant impact on melanoma thickness. Methods Patients with previous melanoma (n = 347, median age at diagnosis: 56.5 years, 44.7% female, 55.3% male) were recruited for this monocentre, non-randomized, observational study between April 2012 and March 2013. All patients were assessed by means of a structured interview and systematic clinical and dermoscopic full-body examination. Melanoma thickness in association with patients' characteristics, risk indicators and patterns of diagnosis was submitted to statistical analyses. Results Univariate analyses revealed associations between a statistically significant lower Breslow thickness and participation in specialized dermoscopic screening programs, personal history of more than one previous melanoma, diagnostic examination with a dermatoscope, diagnostic examination by board certified dermatologist, high number of common and/or atypical nevi, younger age at time of diagnosis, higher level of education, or superficial spreading or lentigo maligna melanoma subtype (all P ≤ 0.01). In a multivariate regression analysis only three of these criteria: (i) participation in specialized screening programs (P < 0.0001); (ii) melanoma subtype (P < 0.0001); and (iii) diagnostic examination with a dermatoscope (P = 0.040) and one interaction term ('younger age' x 'female sex', P < 0.0001) showed an independent influence on a significantly lower melanoma thickness. Conclusions The screening of patients in specialized surveillance programs resulted in melanoma detection at significantly earlier stages. The use of dermoscopy, SSM or LMM histotype and younger age in connection with female sex were also characteristics that were independently associated with significantly thinner melanomas in multivariate analyses. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented that discusses phenotypic and genotypic differentiation of naevus spilus-type congenital melanocytic naevus and segmental naevus spilus.

A letter to the editor is presented which discusses the medical case of a 71-year-old female patient presented with insect bite-like reactions with B-cell chronic lymphocytic leukaemia and was diagnosed with neoplastic B cells through in situ hybridization analysis.

A letter to the editor is presented on a case study of a 41-year-old patient with eccrine poroma or skin tumor.

A letter to the editor is presented regarding a case of phacomatosis spilorosea (PS), its visual diagnosis and related pathologies, in a 12-year-old girl with pigmented skin lesion.