Browsing by Author "Espinoza, Jaime"
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Item High-Grade Patellar Chondral Defects: Promising Results From Management With Osteochondral Autografts(2020-07) Figueroa, David; Calvo, Rafael; Donoso, Rodrigo; Espinoza, Jaime; Vaisman, Alex; Yañez, ClaudioBackground: Patellar chondral defects represent up to 34.6% of defects found during routine arthroscopy. Surgical management has evolved during the past 20 years in an effort to develop techniques to replace hyaline cartilage. Currently, the only technique that achieves this is osteochondral autologous transfer (OAT). Although good and excellent results have often been reported at midterm and long-term follow-up for femoral lesions, little is known about isolated patellar defects. Purpose: To assess clinical and imaging results of patients treated with OAT for high-grade patellar defects. Study Design: Case series; Level of evidence, 4. Methods: This was a retrospective study on all patients who received OAT for high-grade symptomatic patellar chondral defects between 2010 and 2018 at our institution. The study included patients younger than 40 years of age with anterior knee pain and a grade 4 International Cartilage Repair Society patellar chondral defect between 1 and 2.5 cm2. Patients with surgery in other knee compartments, concomitant anterior cruciate ligament ruptures, infection, rheumatoid arthritis, and degenerative lesions were excluded. Six months postoperatively, all patients underwent magnetic resonance imaging (MRI) to allow assessment of graft integrity via the MOCART (Magnetic Resonance Observation of Cartilage Repair Tissue) score to evaluate morphologic features and integration. Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and Kujala scores were used to assess functional outcomes at final follow-up. Results: A total of 26 patients who received a patellar OAT were included. Most patients were male (88.4%), and the mean ± SD age was 28.5 ± 9.7 years. Patellar chondral defects had a median size of 180 mm2 (range, 64-250 mm2), and patients received a median of 1 autograft (range, 1-3). Functional outcomes assessed at a minimum of 1 year after surgery showed a mean Kujala score of 90.42 ± 6.7 and a mean WOMAC score of 95 ± 3.6. MRI revealed a median MOCART score of 75 points (range, 20-90 points). Conclusion: To our knowledge, this is the largest series to date regarding isolated patellar OAT. At midterm follow-up, most patients reported good and excellent results regarding symptoms and activity levels. Most autografts showed good osseous integration and excellent filling of the chondral surface, as evidenced on MRI. OAT is a good alternative to treat high-grade patellar chondral defects, especially among young patients.Item Osteochondral Autologous Transplantation for Treating Patellar High-Grade Chondral Defects: A Systematic Review(SAGE Publications, 2019) Donoso, Rodrigo; Figueroa, David; Espinoza, Jaime; Yáñez, Claudio; Saavedra, JamilBackground: Patellar cartilage defects account for 34.6% of defects found during routine arthroscopy. These defects pose a challenge in orthopaedic surgery because they have been associated with worse outcomes after surgical repair compared with other chondral lesions within the knee. Purpose: To systematically review the literature for evidence on results of osteochondral autologous transplantation (OAT) for the management of isolated patellar cartilage high-grade defects (International Cartilage Repair Society [ICRS] grade 3-4). Study Design: Systematic review; Level of evidence, 4. Methods: A systematic review of the literature was performed to find studies that addressed outcomes regarding OAT to treat patellar high-grade cartilage defects (ICRS grade 3-4). Studies addressing patient-reported outcomes, return to sports, or magnetic resonance imaging (MRI) at follow-up after isolated OAT procedures for patellar cartilage defects were included. Results: A total of 5 studies were included in this review. We were not able to perform a meta-analysis as no studies had available data. A total of 102 patients who received an isolated OAT for a patellar chondral defect were included in these 5 studies. All patients showed significant improvement at final follow-up based on the following patient-reported outcome scores: Lysholm, International Knee Documentation Committee, Kujala, Tegner, and 36-Item Short Form Health Survey. We found that 4 studies used MRI during the first postoperative year to assess osteochondral plug integration and positioning. The results demonstrated that most plugs were integrated and correctly positioned when evaluated at follow-up, conducted on average after 12 months. Whether patients were able to return to sports was queried in 2 of the included studies, revealing that patients could return to their previous level in most cases (Tegner score, 5-9 at 2 years after surgery). Conclusion: Results indicate that OAT is a safe and reliable technique to treat patellar high-grade osteochondral defects, allowing for significant improvement in patient-reported outcomes and return to sports.Item Small molecule inhibitor screening identifified HSP90 inhibitor 17-AAG as potential therapeutic agent for gallbladder cancer(Impact Journals, 2017) Weber, Helga; Valbuena, Jose R.; Barbhuiya, Mustafa A; Stein, Stefan; Kunkel, Hana; Garcia, Patricia; Bizama, Carolina; Riquelme, Ismael; Espinoza, Jaime; Kurtz, Stephen; Tyner, Jeffrey; Calderón, Juan Francisco; Corvalan, Alejandro; Grez, Manuel; Pandey, Akhilesh; Leal-Rojas, Pamela; Roa, Juan C.Gallbladder cancer (GBC) is a lethal cancer with poor prognosis associated with high invasiveness and poor response to chemotherapy and radiotherapy. New therapeutic approaches are urgently needed in order to improve survival and response rates of GBC patients. We screened 130 small molecule inhibitors on a panel of seven GBC cell lines and identified the HSP90 inhibitor 17-AAG as one of the most potent inhibitory drugs across the different lines. We tested the antitumor efficacy of 17-AAG and geldanamycin (GA) in vitro and in a subcutaneous preclinical tumor model NOD-SCID mice. We also evaluated the expression of HSP90 by immunohistochemistry in human GBC tumors.In vitro assays showed that 17-AAG and GA significantly reduced the expression of HSP90 target proteins, including EGFR, AKT, phospho-AKT, Cyclin B1, phospho-ERK and Cyclin D1. These molecular changes were consistent with reduced cell viability and cell migration and promotion of G2/M cell cycle arrest and apoptosis observed in our in vitro studies.In vivo, 17-AAG showed efficacy in reducing subcutaneous tumors size, exhibiting a 69.6% reduction in tumor size in the treatment group compared to control mice (p < 0.05).The HSP90 immunohistochemical staining was seen in 182/209 cases of GBC (87%) and it was strongly expressed in 70 cases (33%), moderately in 58 cases (28%), and weakly in 54 cases (26%).Our pre-clinical observations strongly suggest that the inhibition of HSP90 function by HSP90 inhibitors is a promising therapeutic strategy for gallbladder cancer that may benefit from new HSP90 inhibitors currently in development.