ABSTRACT
INTRODUCTION: Glioblastoma (GBM) is the most common and deadliest primary brain tumor, characterized by chemoradiation resistance and an immunosuppressive tumor microenvironment (TME). SARS-CoV-2, the COVID-19 virus, produces a significant proinflammatory response and a spectrum of clinical presentations after central nervous system infection. METHOD(S): Patient-derived GBM tissue, primary cell lines, and organoids were analyzed with immunohistochemistry and pixel-line intensity quantification. Data from tumor-bulk and single-cell transcriptomics served to describe the cell-specific expression of SARS-CoV-2 receptors in GBM and its association with the immune TME phenotype. Normal brain and iPSC-derived organoids served as controls. RESULT(S): We demonstrate that patient-derivedGBMtissue and cell cultures express SARS-CoV2 entry factors such as ACE2, TMPRSS2, and NRP1. NRP1 expression was higher in GBM than in normal brains (p<0.05), where it plays a crucial role in SARS-CoV-2 infection. NRP1 was expressed in a cell-type and phenotype-specific manner and correlated with TME infiltration of immunosuppressive cells: M2 macrophages (r = 0.229), regulatory T cells (r = 0.459), NK cells (r = -0.346), and endothelial cells (r = 0.288) (p < 0.05). Furthermore, gene ontology enrichment analysis showed that leukocyte migration and chemotaxis are among the top 5 biological functions mediated by NRP1 (p < 0.05). We found our GBM organoids recapitulate tumoral expression of SARSCoV- 2 entry factors, which varies based on distance from surface as surrogate of TME oxygenation (p < 0.05). CONCLUSION(S): GBM cancer cells and immune TME cells express SARS-CoV-2 entry factors. Glioblastoma organoids recapitulate this expression and allow for currently undergoing studies analyzing the effect of SARS-CoV-2 infection in GBM. Our findings suggest that SARSCoV- 2 could potentially target GBM, opening the door to future studies evaluating SARS-CoV-2-driven immune modulation.
ABSTRACT
Purpose/Background: With ERAS protocols advocating for multi-modal non-opiate options, amongst a surging opiate crisis, we reviewed published data to create our own protocol for non-narcotic colorectal surgery. Hypothesis/Aim: Non narcotic options in the perioperative period of colectomy is a viable, safe management plan Methods/Interventions: Our institution implemented an updated ERAS protocol beginning 1/1/2020. Our study was conducted from 7/1/19- 6/30/20. There were two groups, the prior ERAS protocol (p-ERAS) and the current non opiate (c-ERAS) group. Data was collected from 1/1/2019- 6/1/2020, acknowledging the decreased colectomies performed during the Coronavirus pandemic. Any patient during that time who was scheduled for surgery with a preoperative ERAS designation was included. Pain control was reviewed by comparing nursing reported pain scales. Other compared end points between the two groups included: length of stay (LOS), return of bowel function, and outpatient pain control based on the discharge medication orders and the number of patients who requested additional medications. Results/Outcome(s): 134 patients were studied with 25 patients (18.7%) c-ERAS compliant, compared to 109 patients (81.3%) who received opiates. Mean pain scores were reported by nursing as no pain (0), mild (1-3), moderate (4-6), or severe (7-10). A distribution of the duration of time (calculated in hours spent during the different pain levels) was determined for each of the four levels. The c-ERAS group was found to have a significantly longer duration with no pain, 34 vs 23 hours, (p = 0.062). The p-ERAS group was found to have elevated duration of moderate pain, 23.2 hours, in contrast to spending 17.7 and 14.1 hours with mild and severe pain, respectively. Overall, there was a significant time difference favoring the c-ERAS population in time with no pain, moderate pain, and severe pain. There was no statistically significant difference in the average length of stay. Limitations: Small population, only some of the recommended non - narcotic therapy options were available, analyzed pain scales were subjective findings reported to the staff and retrospectively reviewed. Conclusions/Discussion: In 2015, our community-based teaching institution implemented a colorectal ERAS protocol, which was later recognized to be dated. In 2019, a resident driven revision of the ERAS protocol was performed. This resulted in the implementation of a non-opiate colectomy regimen. Aside from immediate pre-operative opiate use by Anesthesia, no other peri-operative opiate medications were routinely ordered. Our regimen included preoperative celecoxib, tylenol, and pregabalin, intraoperative lidocaine infusion, and a postoperative rotation of toradol and IV tylenol, then transition to oral tylenol, and no narcotics prescribed on discharge. With this protocol, we have found a significant time difference favoring the c-ERAS population in time with no pain, moderate pain, and severe pain.