Objective: Pathological angiogenesis is a hallmark of various diseases characterized by local hypoxia and inflammation. These disorders can be treated with inhibitors of angiogenesis, but current compounds display a variety of side effects and lose efficacy over time. This makes the identification of novel signaling pathways and pharmacological targets involved in angiogenesis a top priority. Approach and Results: Here, we show that inactivation of FAAH (fatty acid amide hydrolase), the enzyme responsible for degradation of the endocannabinoid anandamide, strongly impairs angiogenesis in vitro and in vivo. Both, the pharmacological FAAH inhibitor URB597 and anandamide induce downregulation of gene sets for cell cycle progression and DNA replication in endothelial cells. This is underscored by cell biological experiments, in which both compounds inhibit proliferation and migration and evoke cell cycle exit of endothelial cells. This prominent antiangiogenic effect is also of pathophysiological relevance in vivo, as laser-induced choroidal neovascularization in the eye of FAAH −/− mice is strongly reduced. Conclusions: Thus, elevation of endogenous anandamide levels by FAAH inhibition represents a novel antiangiogenic mechanism.

Purpose Besides the multi-layered capsule–ligamentous complex of the elbow joint the high bony congruence in the ulnohumeral joint contributes to elbow stability. Therefore, we assume that specific anatomical configurations of the trochlear notch predispose to dislocation. In case of ligamentous elbow dislocation both conservative and surgical treatment is possible without a clear treatment algorithm. Findings of constitutional bony configurations could help deciding for the best treatment option. Methods In this retrospective matched-pair analysis we compared MRI imaging from patients sustaining a primary traumatic elbow dislocation (instability group) with patients suffering from chronic lateral epicondylitis (control group), treated between 2009 and 2019. Two independent observers measured different anatomical landmarks of the trochlear notch in a multiplanar reconstructed standardized sagittal trochlear plane (SSTP). Primarily, opening angle and relative depth of the trochlear notch were determined. After adjustment to the proximal ulnar rim in the SSTP, coronoid and olecranon angle, the articular angle as well as the ratio of the tip heights of the trochlear notch were measured. Results We compared 34 patients in the instability group (age 48 ± 14 years, f/m 19/15) with 34 patients in the control group (age 47 ± 16 years, f/m 19/15). Instability group showed a significantly larger opening angle (94.1° ± 6.9° vs. 88.5° ± 6.9°, p = 0.0002), olecranon angle (60.9° ± 5.3° vs. 56.1° ± 5.1°, p < 0.0001) and articular angle (24.7° ± 6.4° vs. 22.3° ± 5.8°, p = 0.02) compared to the control group. Measuring the height from the coronoid (ch) and olecranon (oh) tip also revealed a significantly larger tip ratio (tr = ch/oh) in the instability group (2.7 ± 0.8 vs. 2.2 ± 0.5, p < 0.0001). The relative depth (61.0% ± 8.3% vs. 62.7% ± 6.0%, p = 0.21) of the trochlear notch as well as the coronoid angle (32.8° ± 4.5° vs. 31.7° ± 5.2°, p = 0.30) showed no significant difference in the instability group compared to the control group. The interrater reliability of all measurements was between 0.83 and 0.94. Conclusion MRI of patients with elbow dislocation show that there seems to be a bony anatomical predisposition. According to the results, it seems reasonable to include predisposing bony factors in the decision-making process when surgical stabilization and conservative treatment is possible. Further biomechanical studies should prove these assumptions to generate critical bony values helping surgeons with decision making. Level of evidence III.

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ZusammenfassungDie Versorgung von unfallbedingten Notfällen in der Schwangerschaft gehört selbst in überregionalen Traumazentren nicht zur täglichen Routine. Wir präsentieren den Fall einer 27 Jahre alten, nicht vorerkrankten Polytraumapatientin in der 30. Schwangerschaftswoche. Die führende Verletzung war eine Beckenfraktur mit spinopelviner Dissoziation und kreislaufrelevanter, intrapelviner Blutung. Durch ein konsequentes Polytraumamanagement, notfallmäßige Sectio, Ligatur der Corona mortis, Packing und operative Frakturstabilisierung des Beckens konnte das Leben der Mutter und des Kindes gerettet werden.