Background Activating RAS mutations in the germline cause rare developmental disorders such as Costello syndrome. Somatic RAS mutations are found in approximately 30% of human cancers. Keratinocytic epidermal nevi (KEN) represent benign congenital skin lesions arranged along Blaschko's lines. A subgroup of KEN is caused by hotspot oncogenic FGFR3 and PIK3CA mutations in mosaicism, but the majority lack these mutations. Methods This study screened 72 KEN for activating mutations in RAS genes and other oncogenes. Results Activating RAS mutations were identified in 28/72 (39%) of KEN. HRAS was the most commonly affected oncogene (86%), with the HRAS p.G13R substitution representing a new hotspot mutation. Conclusion These results indicate that activating RAS somatic mutations leading to mosaicism result in benign KEN of the skin. Given the prevalence of KEN, mosaic HRAS mutations appear to be more common in patients than germline ones. These findings identify KEN as a mosaic RASopathy and lend further support to the notion that genetic mosaicism is an important contributor to disease.

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Purpose: To evaluate a new isotropic 3D proton-density, turbo-spin-echo sequence with variable flip-angle distribution (PD-SPACE) sequence compared to an isotropic 3D true-fast-imaging with steady-state-precession (True-FISP) sequence and 2D standard MR sequences with regard to the new 3D magnetic resonance observation of cartilage repair tissue (MOCART) score. Materials and Methods:Sixty consecutive MR scans on 37 patients (age: 32.8 6 7.9 years) after matrix-associated autologous chondrocyte transplantation (MACT) of the knee were prospectively included. The 3D MOCART score was assessed using the standard 2D sequences and the multiplanar-reconstruction (MPR) of both isotropic sequences. Statistical, Bonferroni-corrected correlation as well as subjective quality analysis were performed.Results: The correlation of the different sequences was significant for the variables defect fill, cartilage interface, bone interface, surface, subchondral lamina, chondral osteophytes, and effusion (Pearson coefficients 0.514-0.865). Especially between the standard sequences and the 3D True-FISP sequence, the variables structure, signal intensity, subchondral bone, and bone marrow edema revealed lower, not significant, correlation values (0.242-0.383). Subjective quality was good for all sequences (P ! 0.05). Artifacts were most often visible on the 3D True-FISP sequence (P < 0.05).Conclusion: Different isotropic sequences can be used for the 3D evaluation of cartilage repair with the benefits of isotropic 3D MRI, MPR, and a significantly reduced scan time, where the 3D PD-SPACE sequence reveals the best results.

BackgroundThe aim of the study was to evaluate the safety and efficacy of a novel metal-free ceramic total knee replacement system.MethodsThirty-eight primary total knee arthroplasties (TKAs) were performed on 34 patients using the metal-free BPK-S ceramic total knee replacement system with both the femoral and tibial components of an alumina/zirconia ceramic composite. The clinical outcome was evaluated pre- and postoperatively at 3 (n = 32 TKA) and 12 months (n = 32 TKA) using the Knee Society Score (KSS), the Oxford Knee Score and the EQ-5D. Safety analysis was performed by radiological examination and assessment of adverse events.ResultsPostoperatively, the KSS, Oxford Knee Score and EQ-5D improved significantly at 3 and 12 months (p < 0.001). Non-progressive partial radiolucent lines were observed in six cases, but there was no osteolysis and no implant loosening. Induction or exacerbation of allergies did not occur during the follow-up.ConclusionsThe metal-free BPK-S ceramic total knee replacement system proved to be a safe and clinically efficient alternative to metal implants in this short-term follow-up study.

Abstract:Purpose: Repeated failures in melanoma therapy made clear that the molecular mechanisms leading to melanoma are still poorly understood. Here, we aim to provide a more comprehensive understanding of the transcriptional profiles and signaling pathways associated with melanoma.