Objective. To determine the magnetic resonance imaging (MRI), macroscopic, and microscopic characteristics of synovial membrane inflammation, to study the relationship between disease severity and the degree of synovial inflammation on MRI and on macroscopic and microscopic examination, and to look for colocalization of chondral lesions and synovial inflammation.Methods. Thirty-nine patients with knee osteoarthritis (OA) were classified into 2 groups according to the severity of cartilage lesions as revealed by chondroscopy. Group 1 (n ‫؍‬ 14) had mild cartilage lesion(s) without exposure of subchondral bone. Group 2 (n ‫؍‬ 25) had severe cartilage lesion(s) with focal or diffuse exposure of subchondral bone. Synovitis was evaluated on T1-weighted MRI sequences according to the degree of synovial thickening on a 4-point scale (ranging from 0 to 3) in 5 regions of interest. Synovial membrane was macroscopically scored, and biopsies were performed on the 5 preselected sites for histologic scoring.Results. The mean ؎ SD synovial thickening score on MRI was 1.55 ؎ 0.90, with no significant difference between groups 1 and 2. Intra-and interobserver reproducibility of the total synovial score was excellent, and interobserver reproducibility of the MRI grade was good. Conclusion. Synovitis may be present from the onset of OA and may be evaluated on MRI. MRI evaluation of synovitis could be used to classify OA patients in clinical trials and could help to identify those who could benefit from synovium-targeted therapy.Osteoarthritis (OA) is the most prevalent form of arthritis and a major cause of disability worldwide (1).

Purpose Clinical practice guidelines provide recommendations for the management of diseases. In orphan conditions such as uveal melanoma (UM), guideline developers are challenged to provide practical and useful guidance even in the absence of high-quality evidence. Here, we assessed the methodological quality and identified deficiencies of international guidelines on UM as a base for future guideline development. Methods A systematic search was carried out in guideline databases, Medline and Embase until 27th May 2019 for guidelines on UM published between 2004 and 2019. Five independent reviewers assessed the methodological quality of the identified guidelines using the instruments "Appraisal of Guidelines for Research and Evaluation II" (AGREE II) and AGREE-REX (Recommendation EXcellence). Descriptive analysis was performed and subgroup differences were explored with the Kruskal-Wallis (H) test. The relationship between the individual domains and items of the instruments were examined using Spearman's correlation. Results Five guidelines published from 2014 to 2018 by consortia of the United States of America, Canada and the United Kingdom (UK) were included. The highest scores were obtained by the UK guideline fulfilling 48-86% of criteria in AGREE II and 30-60% for AGREE-REX. All guidelines showed deficiencies in the domains "editorial independence", "applicability", and "recommendation". Subgroup differences were identified only for the domain "editorial independence". Conclusion The UK guideline achieved the highest scores with both instruments and may serve as a basis for future guideline development in UM. The domains "editorial independence", "recommendation", and "applicability" were identified as methodological weaknesses and require particular attention and improvement in future guidelines.Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Background: Anti-PD1ebased immunotherapy is currently used in most patients with advanced melanoma. Despite the remarkable data regarding overall survival, the optimal treatment duration is still unknown. Methods: We evaluated the outcome of 125 patients with advanced melanoma with and without brain metastases (MBM), treated either with anti-PD1 monotherapy (N Z 97) or combined with anti-CTLA4 (N Z 28) after elective treatment discontinuation due to complete response (CR) (group A, N Z 86), or treatment-limiting toxicity (N Z 33) and investigator's decision (ID, N Z 6) (group B) with subsequent CR. Results: For group A, median duration of treatment (mDoT) was 22 months (range 5e49) and median time to CR 9 months (range 2e47). Accordingly, mDoT for group B was 3 months (range 0e36) and median time to CR 7 months (range 1e32). Seven patients from group A and three from group B experienced disease recurrence. Off-treatment survival was not reached. Median off-treatment response time (mOTRt) was 19 months (range 0e42) and 25 months (range 0e66), respectively. For MBM, mOTRt was 17 months (range 7e41) and 28 months (range 9e39), respectively. After a median follow-up of 38 months (range 9e70), seven (5.6%) patients had deceased, one (0.8%) due to melanoma. Conclusions: Treatment discontinuation is feasible also in patients with MBM. Efficacy outcomes seemed to be similar in both groups of patients who achieved CR, regardless of reason for discontinuation. In patients who experienced disease relapse, treatment re-challenge with anti-PD1 resulted in subsequent renewed response.

We present the case of a 77-year-old male patient with more than 50 basal cell carcinomas on the head and upper trunk. The patient did not respond to several lines of treatment, including surgery, imiquimod, retinoids, itraconazole and therapy with the hedgehog inhibitor vismodegib. The patient responded well to off-label therapy with the anti-programmed death-1 antibody pembrolizumab after four infusions.