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Objective: Receptor interacting proteins kinase 1 and 3 (RIPK1 and RIPK3) have been shown to play essential roles in the pathogenesis of abdominal aortic aneurysms (AAAs) by mediating necroptosis and inflammation. We previously discovered a small molecular inhibitor GSK2593074A (GSK’074) that binds to both RIPK1 and RIPK3 with high affinity and prevents AAA formation in mice. In this study, we evaluated whether GSK’074 can attenuate progression of existing AAA in the calcium phosphate model. Methods: C57BL6/J mice were subjected to the calcium phosphate model of aortic aneurysm generation. Mice were treated with either GSK’074 (4.65 mg/kg/day) or dimethylsulfoxide (DMSO) controls starting 7 days after aneurysm induction. Aneurysm growth was monitored via ultrasound imaging every 7 days until harvest on day 28. Harvested aortas were examined via immunohistochemistry. The impact of GSK’074 on vascular smooth muscle cells and macrophages were evaluated via flow cytometry and transwell migration assay. Results: At the onset of treatment, mice in both the control (DMSO) and GSK’074 groups showed similar degree of aneurysmal expansion. The weekly ultrasound imaging showed a steady aneurysm growth in DMSO-treated mice. The aneurysm growth was attenuated by GSK’074 treatment. At humane killing, GSK’074-treated mice had significantly reduced progression in aortic diameter from baseline as compared with the DMSO-treated mice (83.2% ± 13.1% [standard error of the mean] vs 157.2% ± 32.0% [standard error of the mean]; P < .01). In addition, the GSK’074-treated group demonstrated reduced macrophages (F4/80, CD206, MHCII), less gelatinase activity, a higher level of smooth muscle cell-specific myosin heavy chain, and better organized elastin fibers within the aortic walls compared with DMSO controls. In vitro, GSK’074 inhibited necroptosis in mouse aortic smooth muscle cells; whereas, it was able to prevent macrophage migration without affecting Il1b and Tnf expression. Conclusions: GSK’074 is able to attenuate aneurysm progression in the calcium phosphate model. The ability to inhibit both vascular smooth muscle cell necroptosis and macrophage migration makes GSK’074 an attractive drug candidate for pharmaceutical treatment of aortic aneurysms. Clinical Relevance: Previous clinical trials evaluating pharmaceutical treatments in blocking aneurysm progression have failed. However, most agents used in those trials focused on inhibiting only one mechanism that contributes to aneurysm pathogenesis. In this study, we found GSK’074 is able to attenuate aneurysm progression in the calcium phosphate model by inhibiting both vascular smooth muscle cell necroptosis and macrophage migration, which are both key processes in the pathogenesis of aneurysm progression. The ability of GSK’0474 to inhibit multiple key pathologic mechan...

Background: Heterotopic ossification (HO), or the abnormal formation of bone in extra-skeletal tissue, is a well-known complication of orthopedic trauma, tendon avulsions, chronic injuries, spinal cord injuries, and soft tissue damage from surgery. Heterotopic ossification commonly develops at the direct or indirect head of the rectus femoris. Athletes are especially susceptible to chronic microtearing and acute tendon avulsion, which may result in HO. When HO develops in the setting of concurrent intra-articular hip pathology, it may be amendable to arthroscopic excision, depending on its size and location. Indications: Heterotopic ossification that develops adjacent to the hip joint can affect range of motion of the joint and is often a source of pain. Arthroscopic excision is indicated when the HO that develops within or about the hip joint is symptomatic and is of a location and size that it can be reached and excised arthroscopically. Technique Description: In this technical note, we describe our method to excise HO using initial arthroscopic surgery to address femoroacetabular impingement syndrome (FAIS) and perform initial dissection of the HO fragment. Heterotopic ossification resection was then completed via an anterior open approach followed by reconstruction of the rectus femoris origin with Achilles allograft. This is followed by our HO prophylaxis protocol of indomethacin 75 mg daily for 4 days, followed by naproxen 500 mg 2 times daily through postoperative day 30, although many other regimens exist for HO prophylaxis. Results: Using arthroscopy for the removal of symptomatic HO at the time of surgery allows for the management of concomitant intra-articular pathology and efficient and precise dissection of the undersurface of the HO fragment. Discussion/Conclusion: Heterotopic ossification is a well-characterized complication of soft tissue damage, including tendon avulsion, trauma, previous surgery, and chronic microtear of the hip musculature. Oftentimes, HO develops in a location that can be reached arthroscopically. Surgeons should consider combining intra-articular arthroscopic surgery with arthroscopic excision of HO when appropriate, noting that there are many advantages to arthroscopic removal when compared with open procedures. Patient Consent Disclosure Statement: The author(s) attests that consent has been obtained from any patient(s) appearing in this publication. If the individual may be identifiable, the author(s) has included a statement of release or other written form of approval from the patient(s) with this submission for publication.

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Osteomyelitis of the patella is a rare disease primarily affecting the pediatric population. Because it often presents with nonspecific symptoms, such as fever and pain, the diagnosis and treatment can be delayed. Prepatellar septic bursitis is also rare in the pediatric population; if left untreated it can progress to patella osteomyelitis. We present a case of prepatellar bursitis that progressed to septic knee arthritis and severe patella osteomyelitis in a 5-year-old male patient. This case demonstrates the importance of further evaluation and close follow up of suspected prepatellar bursitis in pediatric patients with consideration of magnetic resonance imaging (MRI) to monitor for early patella osteomyelitis, an uncommon but treatable disease.