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Browsing by Author "Song, Leo"
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Item Aging- and Tumor-Mediated Increase in CD8+CD28- T Cells Might Impose a Strong Barrier to Success of Immunotherapy in Glioblastoma(American Association of Immunologists, 2021-06-08) Huff, Wei X.; Bam, Marpe; Shireman, Jack M.; Kwon, Jae Hyun; Song, Leo; Newman, Sharlé; Cohen-Gadol, Aaron A.; Shapiro, Scott; Jones, Tamara; Fulton, Kelsey; Liu, Sheng; Tanaka, Hiromi; Liu, Yunlong; Wan, Jun; Dey, Mahua; Neurological Surgery, School of MedicineClinical use of various forms of immunotherapeutic drugs in glioblastoma (GBM), has highlighted severe T-cell dysfunction such as exhaustion in GBM patients. However, reversing T-cell exhaustion using immune checkpoint inhibitors in GBM clinical trials has not shown significant overall survival benefit. Phenotypically, CD8+ T cells with downregulated CD28 co-receptors, low CD27 expression, increased CD57 expression, and telomere shortening, are classified as senescent T cells. These senescent T cells are normally seen as part of aging and also in many forms of solid cancers. Absence of CD28 on T-cells leads to several functional irregularities including reduced TCR diversity, incomplete activation of T cells, and defects in antigen induced proliferation. In the context of GBM, presence and/or function of these CD8+CD28− T-cells is unknown. In this clinical correlative study, we investigated the effect of aging as well as tumor microenvironment on CD8+ T-cell phenotype as an indicator of its function in GBM patients. We systematically analyzed and describe a large population of CD8+CD28− T-cells in both the blood and tumor infiltrating lymphocytes of GBM patients. We found that phenotypically these CD8+CD28− T-cells represent a distinct population compared to exhausted T-cells. Comparative transcriptomic and pathway analysis of CD8+CD28− T cell populations in GBM patients revealed that tumor microenvironment might be influencing several immune related pathways and thus further exaggerating the age associated immune dysfunction in this patient population.Item Robotic Sacral Colpopexy Using Autologous Fascia Lata Compared with Mesh(Liebert, 2020) Bock, Megan E.; Nagle, Ramzy; Soyster, Mary; Song, Leo; Tachibana, Isamu; Hathaway, Jon K.; Powell, Charles R.; Urology, School of MedicineObjective: The objective is to compare robotic sacral colpopexy (RSC) utilizing autologous fascia lata with RSC with synthetic mesh in the treatment of pelvic organ prolapse (POP). Methods: We performed a prospective nonrandomized case comparison trial at a single institution. We compared RSC utilizing either synthetic mesh or autologous fascia lata in women with symptomatic POP, stages II through IV. The primary outcome was anatomic prolapse recurrence determined by the Pelvic Organ Prolapse Quantification (POP-Q) examination. Secondary outcomes included patient-reported outcomes such as the Urogenital Distress Inventory-6 (UDI-6) and Incontinence Impact Questionnaire-7 (IIQ-7). Complications were also recorded and categorized using the Clavien–Dindo (CD) system. The hypothesis is that autologous fascia lata would provide equivalent anatomic and patient-reported outcomes compared with mesh while eliminating mesh-related complications. Results: Sixty-four women underwent RSC with 19 (29.7%) receiving fascia lata graft. The overall operative time was greater in the fascia lata group with mean fascia lata harvest time of 24.8 ± 7.4 minutes. Intragroup comparisons of the fascia and mesh groups demonstrated significant improvement in pelvic measurements as well as patient-reported outcomes. Intergroup comparison demonstrated equivalent success rates at 12.1 ± 8.7 months follow-up. There was one apical failure in the fascia lata RSC group; however, the difference was not statistically significant (p = 0.30). Significant complications in the fascia lata harvest group included two CD-II and one CD-IIIb. In the mesh group there was one mesh erosion requiring surgical excision (CD-IIIb). Conclusion: This is the first comparison between RSC with autologous fascia lata and mesh. Short-term anatomic outcomes were similar with autologous fascia lata use without the risk of mesh erosion. Morbidity from graft harvest site was not trivial. These results emphasize the need for a randomized controlled trial.