Threshold Optimization for Tumor Markers S100b and MIA in Uveal Melanoma - A Single Center Analysis.

BACKGROUND/AIM: Uveal melanoma (UM) is the most common malignant tumor of the eye in adults. Metastases develop in 50% of the patients, predominantly in the liver. In UM, the cut-off concentrations of the blood-based tumor markers S100b and MIA are inconclusive. PATIENTS AND METHODS: In this retrospective monocenter study, we statistically evaluated 1,878 S100b and 1,768 MIA measurements in 244 patients with UM from 2011-2020. Threshold optimization was performed using receiver operating characteristic (ROC) curves. RESULTS: A total of 171 patients with non-metastatic UM (nmUM) and 73 patients with metastatic UM (mUM) showed no differences in sex, age at diagnosis or the affected eye. In mUM, 80% of the patients developed metastases to the liver at a median of 46 months after initial diagnosis. The sensitivity and specificity of S100b was 16.10% and 94.52%, and that of MIA was 31.86% and 81.42%, respectively. ROC curves revealed poor values for the area under the curve of 0.57 for S100b and 0.55 for MIA. The optimal cut-off concentration to detect metastases was 0.14 µg/l for S100b and 17.4 ng/ml for MIA. With at least one tumor marker elevated, optimized sensitivity was 20.40% and specificity 96.76%. CONCLUSION: Current thresholds for S100b and MIA in UM are not able to detect early metastatic disease and require additional diagnostics to clarify false positive results. Threshold optimization considering both S100b and MIA results in a better diagnostic validity with an acceptable specificity and a poor sensitivity. Highly sensitive blood-based and imaging methods to detect metastases early in UM are urgently needed.

Poor Adherence to Self-Applied Topical Drug Treatment Is a Common Source of Low Lesion Clearance in Patients with Actinic Keratosis-A Cross-Sectional Study.

BACKGROUND: Many treatments for actinic keratosis (AK) have been proven efficient in clinical trials. However, patients with AK may still experience unsatisfactory therapeutic outcomes in clinical practice. OBJECTIVES: To investigate patient adherence to self-applied topical interventions for AK and to explore factors associated with adherence in a real-world setting. METHODS: A cross-sectional study was conducted. Patients presenting with AK were asked to complete a self-administered questionnaire about their last topical AK treatment. RESULTS: A total of 113 patients participated with a median age of 78.5 years (range 58-94). Fifty-four patients (47.8%) received topical diclofenac, ten (8.8%) imiquimod, nine (8%) 5-fluorouracil, nine (8%) 5-fluorouracil plus salicylic acid, and eight (7.1%) photodynamic therapy. The non-adherence rate was 46.9% (n = 53), and only 30.9% (n = 35) used the topical treatments according to the summary of product characteristics (SmPC). These subgroups were compared. Patients of the non-compliant group were significantly less informed about the application time of the specific topical intervention (p = 0.002) and adjusted the timeframe (p < 0.001) and application frequency of the therapy (p = 0.02) independently of their physician. Conversely, patients reporting a sufficient pre-treatment consultation (p = 0.019) generally complied with the SmPC compliance application. CONCLUSIONS: A thorough pre-treatment consultation can help to increase treatment adherence and ensure lesion clearance.

eImmunonkologie: Development and Launch of a Virtual Education Platform for the Immunotherapy of Cutaneous Neoplasms.

The use of immunotherapies in clinical practice has significantly expanded treatment options and improved the prognosis of patients with advanced cancers over the past decade. We have developed a virtual teaching module entitled "eImmunonkologie" which is the first interdisciplinary virtual course on immuno-oncology for medical students in German-speaking countries.

A Critical Appraisal of Evidence- and Consensus-Based Guidelines for Actinic Keratosis.

Actinic keratoses (AK) are common lesions of the skin that can be effectively treated with several lesion- and field-directed treatments. Clinical practice guidelines assist physicians in choosing the appropriate treatment options for their patients. Here, we aimed to systematically identify and evaluate the methodological quality of currently available guidelines for AK. Guidelines published within the last 5 years were identified in a systematic search of guideline databases, Medline and Embase. Then, six independent reviewers evaluated the methodological quality using the tools "Appraisal of Guidelines for Research and Evaluation" (AGREE II) and "Recommendation EXcellence" (AGREE-REX). The Kruskal-Wallis (H) test was used to explore differences among subgroups and Spearman's correlation to examine the relationship between individual domains. Three guidelines developed by consortia from Canada, Germany and the United Kingdom were eligible for the evaluation. The German guideline achieved the highest scores, fulfilling 65 to 92% of the criteria in AGREE II and 67 to 84% in AGREE-REX, whereas the Canadian guideline scored 31 to 71% of the criteria in AGREE II and 33 to 46% in AGREE-REX. The domains "stakeholder involvement" and "values and preferences" were identified as methodological weaknesses requiring particular attention and improvement in future guideline efforts.

Preformed Donor-Specific HLA Antibodies in Living and Deceased Donor Transplantation: A Multicenter Study.

BACKGROUND AND OBJECTIVES: The prognostic value of preformed donor-specific HLA antibodies (DSA), which are only detectable by sensitive methods, remains controversial for kidney transplantation. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: The outcome of 4233 consecutive kidney transplants performed between 2012 and 2015 in 18 German transplant centers was evaluated. Most centers used a stepwise pretransplant antibody screening with bead array tests and differentiation of positive samples by single antigen assays. Using these screening results, DSA against HLA-A, -B, -C, -DRB1 and -DQB1 were determined. Data on clinical outcome and possible covariates were collected retrospectively. RESULTS: Pretransplant DSA were associated with lower overall graft survival, with a hazard ratio of 2.53 for living donation (95% confidence interval [95% CI], 1.49 to 4.29; P<0.001) and 1.59 for deceased donation (95% CI, 1.21 to 2.11; P=0.001). ABO-incompatible transplantation was associated with worse graft survival (hazard ratio, 2.09; 95% CI, 1.33 to 3.27; P=0.001) independent from DSA. There was no difference between DSA against class 1, class 2, or both. Stratification into DSA <3000 medium fluorescence intensity (MFI) and DSA ≥3000 MFI resulted in overlapping survival curves. Therefore, separate analyses were performed for 3-month and long-term graft survival. Although DSA <3000 MFI tended to be associated with both lower 3-month and long-term transplant survival in deceased donation, DSA ≥3000 MFI were only associated with worse long-term transplant survival in deceased donation. In living donation, only strong DSA were associated with reduced graft survival in the first 3 months, but both weak and strong DSA were associated with reduced long-term graft survival. A higher incidence of antibody-mediated rejection within 6 months was only associated with DSA ≥3000 MFI. CONCLUSIONS: Preformed DSA were associated with an increased risk for graft loss in kidney transplantation, which was greater in living than in deceased donation. Even weak DSA <3000 MFI were associated with worse graft survival. This association was stronger in living than deceased donation.