Collagen plays a key structural role in both the annulus fibrosus (AF) and nucleus pulposus (NP) of intervertebral disks (IVDs). Changes in collagen content with degeneration suggest a shift from collagen type II to type I within the NP, and the activation of pro-inflammatory factors is indicative of fibrosis throughout. While IVD degeneration is considered a fibrotic process, an increase in collagen content with degeneration, reflective of fibrosis, has not been demonstrated. Additionally, changes in collagen content and structure in human IVDs with degeneration have not been characterized with high spatial resolution. The collagen content of 23 human lumbar L2/3 or L3/4 IVDs was quantified using second harmonic generation imaging (SHG) and multiple image processing algorithms, and these parameters were correlated with the Rutges histological degeneration grade. In the NP, SHG intensity increased with degeneration grade, suggesting fibrotic collagen deposition. In the AF, the entropy of SHG intensity was reduced with degeneration indicating increased collagen uniformity and suggesting less-organized lamellar structure. Collagen orientation entropy decreased throughout most IVD regions with increasing degeneration grade, further supporting a loss in collagen structural complexity. Overall, SHG imaging enabled visualization and quantification of IVD collagen content and organization with degeneration. There was an observed shift from an initially complex structure to more uniform structure with loss of microstructural elements and increased NP collagen polarity, suggesting fibrotic remodeling.

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.

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INTRODUCTION The ideal timing from admission of a thoracolumbar spinal trauma patient to the start of surgery at US trauma centers remains a hotly contested area of debate. The effect of surgical latency on patient outcomes in thoracolumbar trauma remains unclear. METHODS All 2013 to 2015 thoracolumbar spinal trauma cases from the American College of Surgeons Trauma Quality Improvement Program (TQIP) were analyzed. Patients with unsurvivable spine injury, polytraumas (serious injuries in more than one bodily region), and those discharged within 24 h were excluded. Patients were classified into 3 groups by surgery timing: less than 8 h (early, N = 1699), between 8 and 24 h (normal, N = 946), and over 24 h (delayed, N = 1601). Mortality, length of stay (LOS), and complication rates were compared between groups. Demographic variables and complication rates were compared. Multivariate logistic regression was utilized to determine the specific effect of surgery timing on outcomes. RESULTS Patients with earlier surgery presented with more severe spinal trauma (P < .0001). Patients in the normal surgical timing cohort were most likely to have altered mental status (4.97% vs 3.24%, P = .05), and less likely to suffer from UTI (4.97% vs 3.24%, P = .03). Patients in the delayed cohort were older (46.2 vs 43.7 yr, P = .0003), more likely to have a longer LOS (11.3 vs 10.6 d, P = .02), return to the ICU (2.94% vs 1.29%, P = .001), experience unplanned intubation (2.06% vs 1%, P = .01) and suffer from cardiac arrest (0.53% vs 1.19%, P = .04). Upon multivariate analysis, delayed surgery was an independent risk factor for prolonged LOS (OR: 1.21, 95% CI: 0.56-1.87, P = .0003). CONCLUSION Patients with earlier surgery possessed more severe spinal injury. When adjusting for demographics and severity, no significant difference is seen in mortality between the different surgery times; however, LOS is prolonged in patients with delayed surgery.

To preliminarily evaluate the efficacy and safety of adding PD-1 inhibitor SHR-1210 to chemoradiotherapy in patients with locally advanced cholangiocarcinoma. Materials/Methods: Patients with confirmed diagnosis of locally advanced cholangiocarcinoma based on histopathological and radiological features were included in the study. Patients received a total dose of 50 −60 Gy in 25−30 fractions with concurrent capecitabine (825 mg/m 2 , po, bid) and SHR-1210 (200mg, iv, q2w) on days of radiation. Further consolidation chemotherapy was initiated after completion of radiotherapy and included 4 cycles of gemcitabine (1000 mg/m 2 , iv, Day 1, 8) and cisplatin (75 mg/m 2 , iv, with total volume divided at Day 1-3) in a 21-day cycle with SHR-1210 (200mg, iv, q3w). All patients received study treatment until SHR-1210 was administered for up to 12 months or until disease progression, unacceptable toxicity, or withdrawal of consent. Results: From November 2019 to October 2020, 10 patients were enrolled in the study (6 male [60%], median age, 56 [range, 50-66] years, 4 IIIb stage, 6 IIIc stage). All patients completed radiotherapy. Six patients (60%) experienced myelosuppression, including two with grade 4 advert events (AEs), one stopped chemotherapy and one stopped study treatment. Four patients (40%) developed grade 2 gastrointestinal tract reactions, and the incidence of grade ≤ 3 reactive cutaneous capillary endothelial proliferation (RCCEP) was 100%. All patients had an apparent decrease in the tumor markers CEA and CA-199 levels with symptoms significantly relieved as response to treatment. Among 10 patients treated, 0 (0%) exhibited complete response (CR), 5 (50%) exhibited partial response (PR), 4 (40%) exhibited stable disease (SD) and 1 (10%) exhibited disease progression (PD). The 6-month progression-free survival rate (PFS) was 90%. Conclusion: These findings suggest that combined treatment with PD-1inhibitors and chemoradiotherapy for locally advanced cholangiocarcinoma is tolerable and effective, which provides a new strategy for the treatment of locally advanced cholangiocarcinoma.