- Browse by Author
Browsing by Author "Rajasekaran, Karthik"
Now showing 1 - 2 of 2
Results Per Page
Sort Options
Item Complications, Mortality, and Functional Decline in Patients 80 Years or Older Undergoing Major Head and Neck Ablation and Reconstruction(Silverchair, 2019-10-10) Fancy, Tanya; Huang, Andrew T.; Kass, Jason I.; Lamarre, Eric D.; Tassone, Patrick; Mantravadi, Avinash V.; Alwani, Mohamedkazim M.; Subbarayan, Rahul S.; Bur, Andrés M.; Worley, Mitchell L.; Graboyes, Evan M.; McMullen, Caitlin P.; Azoulay, Ofer; Wax, Mark K.; Cave, Taylor B.; Al-khudari, Samer; Abello, Eric H.; Higgins, Kevin M.; Ryan, Jesse T.; Orzell, Susannah C.; Goldman, Richard A.; Vimawala, Swar; Fernandes, Rui P.; Abdelmalik, Michael; Rajasekaran, Karthik; L’Esperance, Heidi E.; Kallogjeri, Dorina; Rich, Jason T.; Otolaryngology -- Head and Neck Surgery, School of MedicineImportance Data regarding outcomes after major head and neck ablation and reconstruction in the growing geriatric population (specifically ≥80 years of age) are limited. Such information would be extremely valuable in preoperative discussions with elderly patients about their surgical risks and expected functional outcomes. Objectives To identify patient and surgical factors associated with 30-day postoperative complications, 90-day mortality, and 90-day functional decline; to explore whether an association exists between the type of reconstructive procedure and outcome; and to create a preoperative risk stratification system for these outcomes. Design, Setting, and Participants This retrospective, multi-institutional cohort study included patients 80 years or older undergoing pedicle or free-flap reconstruction after an ablative head and neck surgery from January 1, 2015, to December 31, 2017, at 17 academic centers. Data were analyzed from February 1 through April 20, 2019. Main Outcomes and Measures Thirty-day serious complication rate, 90-day mortality, and 90-day decline in functional status. Preoperative comorbidity and frailty were assessed using the American Society of Anesthesiologists classification, Adult Comorbidity Evaluation–27 score, and Modified Frailty Index. Multivariable clustered logistic regressions were performed. Conjunctive consolidation was used to create a risk stratification system. Results Among 376 patients included in the analysis (253 [67.3%] men), 281 (74.7%) underwent free-flap reconstruction. The median age was 83 years (range, 80-98 years). A total of 193 patients (51.3%) had 30-day serious complications, 30 (8.0%) died within 90 days, and 36 of those not dependent at baseline declined to dependent status (11.0%). Type of flap (free vs pedicle, bone vs no bone) was not associated with these outcomes. Variables associated with worse outcomes were age of at least 85 years (odds ratio [OR] for 90-day mortality, 1.19 [95% CI 1.14-1.26]), moderate or severe comorbidities (OR for 30-day complications, 1.80 [95% CI, 1.34-2.41]; OR for 90-day mortality, 3.33 [95% CI, 1.29-8.60]), body mass index (BMI) of less than 25 (OR for 30-day complications, 0.95 [95% CI, 0.91-0.99]), high frailty (OR for 30-day complications, 1.72 [95% CI, 1.10-2.67]), duration of surgery (OR for 90-day functional decline, 2.94 [95% CI, 1.81-4.79]), flap failure (OR for 90-day mortality, 3.56 [95% CI, 1.47-8.62]), additional operations (OR for 30-day complications, 5.40 [95% CI, 3.09-9.43]; OR for 90-day functional decline, 2.94 [95% CI, 1.81-4.79]), and surgery of the maxilla, oral cavity, or oropharynx (OR for 90-day functional decline, 2.51 [95% CI, 1.30-4.85]). Age, BMI, comorbidity, and frailty were consolidated into a novel 3-tier risk classification system. Conclusions and Relevance Important demographic, clinical, and surgical characteristics were found to be associated with postoperative complications, mortality, and functional decline in patients 80 years or older undergoing major head and neck surgery. Free flap and bony reconstruction were not independently associated with worse outcomes. A novel risk stratification system is presented.Item Early, precise, and safe clinical evaluation of the pharmacodynamic effects of novel agents in the intact human tumor microenvironment(Frontiers Media, 2024-04-12) Gundle, Kenneth R.; Rajasekaran, Karthik; Houlton, Jeffrey; Deutsch, Gary B.; Ow, Thomas J.; Maki, Robert G.; Pang, John; Nathan, Cherie-Ann O.; Clayburgh, Daniel; Newman, Jason G.; Brinkmann, Elyse; Wagner, Michael J.; Pollack, Seth M.; Thompson, Matthew J.; Li, Ryan J.; Mehta, Vikas; Schiff, Bradley A.; Wenig, Barry I.; Swiecicki, Paul L.; Tang, Alice L.; Davis, Jessica L.; van Zante, Annemieke; Bertout, Jessica A.; Jenkins, Wendy; Turner, Atticus; Grenley, Marc; Burns, Connor; Frazier, Jason P.; Merrell, Angela; Sottero, Kimberly H. W.; Derry, Jonathan M. J.; Gillespie, Kate C.; Mills, Bre; Klinghoffer, Richard A.; Pathology and Laboratory Medicine, School of MedicineIntroduction: Drug development is systemically inefficient. Research and development costs for novel therapeutics average hundreds of millions to billions of dollars, with the overall likelihood of approval estimated to be as low as 6.7% for oncology drugs. Over half of these failures are due to a lack of drug efficacy. This pervasive and repeated low rate of success exemplifies how preclinical models fail to adequately replicate the complexity and heterogeneity of human cancer. Therefore, new methods of evaluation, early in the development trajectory, are essential both to rule-in and rule-out novel agents with more rigor and speed, but also to spare clinical trial patients from the potentially toxic sequelae (high risk) of testing investigational agents that have a low likelihood of producing a response (low benefit). Methods: The clinical in vivo oncology (CIVO®) platform was designed to change this drug development paradigm. CIVO precisely delivers microdose quantities of up to 8 drugs or combinations directly into patient tumors 4–96 h prior to planned surgical resection. Resected tissue is then analyzed for responses at each site of intratumoral drug exposure. Results: To date, CIVO has been used safely in 6 clinical trials, including 68 subjects, with 5 investigational and 17 approved agents. Resected tissues were analyzed initially using immunohistochemistry and in situ hybridization assays (115 biomarkers). As technology advanced, the platform was paired with spatial biology analysis platforms, to successfully track anti-neoplastic and immune-modulating activity of the injected agents in the intact tumor microenvironment. Discussion: Herein we provide a report of the use of CIVO technology in patients, a depiction of the robust analysis methods enabled by this platform, and a description of the operational and regulatory mechanisms used to deploy this approach in synergistic partnership with pharmaceutical partners. We further detail how use of the CIVO platform is a clinically safe and scientifically precise alternative or complement to preclinical efficacy modeling, with outputs that inform, streamline, and de-risk drug development.