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Background: Apart from eccentric exercises (EE), isometric exercises (ISO) might be a treatment option for Achilles tendinopathy. Shear wave elastography (SWE) provides information for diagnosis and for monitoring tissue elasticity, which is altered in symptomatic tendons. Hypothesis: Isometric exercises will have a beneficial effect on patients’ outcome scores. Based on SWE, insertional and midportion tendon parts will differ in their elastic properties according to current symptoms. Study Design: Randomized clinical trial. Level of Evidence: Level 2. Methods: Group 1 (EE; n = 20; 12 males, 8 females; mean age, 52 ± 8.98 years) and group 2 (EE + ISO; n = 22; 15 males, 7 females; mean age, 47 ± 15.11 years) performed exercises for 3 months. Measurement points were before exercises were initiated as well as after 1 and 3 months using the Victorian Institute of Sports Assessment–Achilles (VISA-A) score, American Orthopaedic Foot & Ankle Society score, and SWE (insertion and midportion). Results: Both groups improved significantly, but there were no significant interindividual differences (VISA-A; P = 0.362) between group 1 (n = 15; +15 VISA-A) and group 2 (n = 15; +15 VISA-A). The symptomatic insertion (symptomatic, 136.89 kPa; asymptomatic, 174.68 kPa; P = 0.045) and the symptomatic midportion of the Achilles tendon (symptomatic, 184.40 kPa; asymptomatic, 215.41 kPa; P = 0.039) had significantly lower Young modulus compared with the asymptomatic tendons. The midportion location had significantly higher Young modulus than the insertional part of the tendon ( P = 0.005). Conclusion: Isometric exercises do not have additional benefit when combined with eccentric exercises, as assessed over a 3-month intervention period. SWE is able to distinguish between insertional and midportion tendon parts in a symptomatic and asymptomatic state. Clinical Relevance: The present study shows no additional effect of ISO when added to baseline EE in treating Achilles tendinopathy. Different elastic properties of the insertional and midportion tendon have to be taken into consideration when rating a tendon as pathologic.

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The KIT D816V mutation is found in more than 80% of patients with systemic mastocytosis (SM) and is key to neoplastic mast cell (MC) expansion and accumulation in affected organs. KIT D816V therefore represents a prime therapeutic target for SM. Here we generated a panel of patient-specific KIT D816V induced pluripotent stem cells (iPSCs) from patients with aggressive SM (ASM) and mast cell leukemia (MCL) to develop a patient-specific SM disease model for mechanistic and drug discovery studies. KIT D816V iPSCs differentiated into neoplastic hematopoietic progenitor cells and MCs with patient-specific phenotypic features, thereby reflecting the heterogeneity of the disease. CRISPR/Cas9n-engineered KIT D816V human embryonic stem cells (ESCs), when differentiated into hematopoietic cells, recapitulated the phenotype observed for KIT D816V iPSC hematopoiesis. KIT D816V causes constitutive activation of the KIT tyrosine kinase receptor and we exploited our iPSCs and ESCs to investigate new tyrosine kinase inhibitors targeting KIT D816V. Our study identified nintedanib, an FDA approved angiokinase inhibitor that targets VEGFR, PDGFR and FGFR, as a novel KIT D816V inhibitor. Nintedanib selectively reduced the viability of iPSC-derived KIT D816V hematopoietic progenitor cells and MCs in the nanomolar range. Nintedanib was also active on primary samples of KIT D816V SM patients. Molecular docking studies show that nintedanib binds to the ATP binding pocket of inactive KIT D816V. Our results suggest nintedanib as a new drug candidate for KIT D816V targeted therapy of advanced SM.

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Introduction Femoroacetabular impingement (FAI) is thought to play an important role in the development of hip osteoarthritis. However, there is no consensus about the optimal treatment options, since non-operative therapy such as physiotherapy and surgical treatment such as arthroscopic hip surgery can both improve symptoms. Therefore, the aim of the present meta-analysis was to compare the outcomes between two different treatment regimes; physiotherapy versus arthroscopic treatment for FAI. Methods The present meta-analysis was carried out according to the PRISMA guidelines. In November 2019, the main online databases were accessed. All the randomized clinical trials (RCTs) comparing surgical arthroscopic treatment versus physiotherapy for FAI were considered for inclusion. Only articles reporting quantitative data under the outcomes of interest were included. For the all analysis, we used Review Manager Software. Data from 644 patients were analysed. Results Data from 644 patients were evaluated with a mean follow-up of 14.67 ± 8.3 months. The unpaired t test detected an optimal baseline comparability in terms of side, gender, years, duration of symptoms and BMI (p = 0.08–0.9). The VAS subscale of the score EQ-5D and the mean iHOT33 reported favourable values in the arthroscopic group (p = 0.03 and p < 0.0001, respectively). Similar findings were evidenced in the iHOT33 subgroup 6-months (p = 0.70) and 12-months (p = 0.0002). The HOS score, the ADL (p < 0.0001) and the sport (p = 0.0003) subscales reported both greater values in the arthroscopic group. No statistical significance was found concerning the risk to incur in further total hip arthroplasty (p = 0.72). Conclusion Based on only three high-quality RCTs, arthroscopic hip surgery is an effective therapeutic treatment for FAI revealing superior results than a non-surgical approach with physiotherapy.