SUMMARY In vitro cancer cultures, including 3-dimensional organoids, typically contain exclusively neoplastic epithelium but require artificial reconstitution to recapitulate the tumor microenvironment (TME). The co-culture of primary tumor epithelia with endogenous, syngeneic tumor-infiltrating lymphocytes (TILs) as a cohesive unit has been particularly elusive. Here, an air-liquid interface (ALI) method propagated Patient-Derived Organoids (PDOs) from >100 human biopsies or mouse tumors in syngeneic immunocompetent hosts as tumor epithelia with native embedded immune cells (T, B, NK, macrophages). Robust droplet-based, single cell simultaneous determination of gene expression and immune repertoire indicated that PDO TILs accurately preserved the original tumor T cell receptor (TCR) spectrum. Crucially, human and murine PDOs successfully modeled immune checkpoint blockade (ICB) with anti-PD-1- and/or anti-PD-L1 expanding and activating tumor antigen-specific TILs and eliciting tumor cytotoxicity. Organoid-based propagation of primary tumor epithelium en bloc with endogenous immune stroma should enable immunooncology investigations within the TME and facilitate personalized immunotherapy testing.

Study Design. Retrospective, observational study of clinical outcomes at a single institution. Objective. To compare postoperative complication and readmission rates of payer groups in a cohort of patients undergoing anterior cervical discectomy and fusion (ACDF). Summary of Background Data. Studies examining associations between primary payer and outcomes in spine surgery have been equivocal. Methods. Patients at Mount Sinai having undergone ACDF from 2008 to 2016 were queried and assigned to one of five insurance categories: uninsured, managed care, commercial indemnity insurance, Medicare, and Medicaid, with patients in the commercial indemnity group serving as the reference cohort. Multivariable logistic regression equations for various outcomes with the exposure of payer were created, controlling for age, sex, American Society of Anesthesiology Physical Status Classification (ASA Class), the Elixhauser Comorbidity Index, and number of segments fused. A Bonferroni correction was utilized, such that alpha = 0.0125. Results. Two thousand three hundred eighty seven patients underwent ACDF during the time period. Both Medicare (P < 0.0001) and Medicaid (P < 0.0001) patients had higher comorbidity burdens than commercial patients when examining ASA Class. Managed care (2.86 vs. 2.72, P = 0.0009) and Medicare patients (2.99 vs. 2.72, P < 0.0001) had more segments fused on average than commercial patients. Medicaid patients had higher rates of prolonged extubation (odds ratio [OR]: 4.99; 95% confidence interval [CI]: 1.13–22.0; P = 0.007), and Medicare patients had higher rates of prolonged length of stay (LOS) (OR: 2.44, 95% CI: 1.13–5.27%, P = 0.004) than the commercial patients. Medicaid patients had higher rates of 30- (OR: 4.12; 95% CI: 1.43–11.93; P = 0.0009) and 90-day (OR: 3.28; 95% CI: 1.34–8.03; P = 0.0009) Emergency Department (ED) visits than the commercial patients, and managed care patients had higher rates of 30-day readmission (OR: 3.41; 95% CI: 1.00–11.57; P = 0.0123). Conclusion. Medicare and Medicaid patients had higher rates of prolonged LOS and postoperative ED visits, respectively, compared with commercial patients. Level of Evidence: 3

No abstract

OBJECTIVEThe authors set out to conduct the first national-level study assessing the risks and outcomes for different lumbar fusion procedures in patients with opioid use disorders (OUDs) to help guide the future development of targeted enhanced recovery after surgery (ERAS) protocols for this unique population.METHODSData for patients with or without OUDs who underwent an anterior lumbar interbody fusion (ALIF), posterior lumbar interbody fusion (PLIF), or lateral transverse lumbar interbody fusion (LLIF) for lumbar disc degeneration (LDD) were collected from the 2013–2014 National (Nationwide) Inpatient Sample database. Multivariable logistic regression was implemented to analyze how OUD status impacted in-hospital complications, length of hospital stay, discharge disposition, and total charges by procedure type.RESULTSA total of 139,995 patients with LDD were identified, with 1280 patients (0.91%) also having a concurrent OUD diagnosis. Overall complication rates were higher in OUD patients (48.44% vs 31.01%, p < 0.0001). OUD patients had higher odds of pulmonary (p = 0.0006), infectious (p < 0.0001), and hematological (p = 0.0009) complications. Multivariate regression modeling of outcomes by procedure type showed that after ALIF, OUD patients had higher odds of nonhome discharge (p = 0.0007), extended hospitalization (p = 0.0002), and greater total charges (p = 0.0054). This analysis also revealed that OUD patients faced higher odds of complication (p = 0.0149 and p = 0.0471), extended hospitalization (p = 0.0439 and p = 0.0001), and higher total charges (p < 0.0001 and p < 0.0001) after PLIF and LLIF procedures, respectively.CONCLUSIONSObtaining a better understanding of the risks and outcomes that OUD patients face perioperatively is a necessary step toward developing more effective ERAS protocols for this vulnerable population. This study, which sought to characterize the outcome profiles for lumbar fusion procedures in OUD patients on a national level, found that this population tended to experience increased odds of complications, extended hospitalization, nonhome discharge, and higher total costs. Results from this study warrant future prospective studies to better the understanding of these associations and to further the development of better ERAS programs that may improve patient care and reduce cost burden.

Study Design: Retrospective cohort study. Objective: The present study analyzes complication rates and episode-based costs for patients with and without diabetes mellitus (DM) following posterior lumbar fusion (PLF). Methods: PLF cases at a single institution from 2008 to 2016 were queried (n = 3226), and demographic and perioperative data were analyzed. Patients with and without the diagnosis of DM were compared using chi-square, Student’s t test, and multivariable regression modeling. Results: Patients with diabetes were older (63.10 vs 56.48 years, P < .001) and possessed a greater number of preoperative comorbidities (47.84% of patients had Elixhauser Comorbidity Index >0 vs 42.24%, P < .001) than did patients without diabetes. When controlling for preexisting differences, diabetes remained a significant risk factor for prolonged length of stay (OR = 1.59, 95% CI 1.26-2.01, P < .001), intensive care unit stay (OR = 1.52, 95% CI 1.07-2.17, P = .021), nonhome discharge (OR = 1.86, 95% CI 1.46-2.37, P < .001), 30-day readmission (OR = 2.15, 95% CI 1.28-3.60, P = .004), 90-day readmission (OR = 1.65, 95% CI 1.05-2.59, P = .031), 30-day emergency room visit (OR = 2.15, 95% CI 1.27-3.63, P = .004), and 90-day emergency room visit (OR = 2.27, 95% CI 1.41-3.65, P < .001). Cost modeling controlling for overall comorbidity burden demonstrated that diabetes was associated with a $1709 increase in PLF costs (CI $344-$3074, P = .014). Conclusions: The present findings indicate a correlation between diabetes and a multitude of postoperative adverse outcomes and increased costs, thus illustrating the substantial medical and financial burdens of diabetes for PLF patients. Future studies should explore preventive measures that may mitigate these downstream effects.