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Background The current management of large, high-grade soft tissue sarcoma (STS) of the trunk and extremities includes radiation and surgical resection. The initial use of chemotherapy and targeted therapy are controversial and although most patients present with localized disease, many eventually develop incurable metastases. The results and analysis of the safety and antitumor activity of combined checkpoint inhibitor immunotherapy with neoadjuvant radiation for high-risk primary STS are presented here. Methods This was an integrated phase I/II prospective single-arm trial (Nutrition and Exercise in Critical Illness Trial (NEXIS) trial). Eligible patients were age ≥18 years with histologically confirmed intermediate or high-grade STS of the trunk or extremity ≥5 cm diameter and were Eastern Cooperative Oncology Group performance status 0-1. The treatment algorithm included neoadjuvant anti-PD-L1 (Durvalumab) and anti-CTLA-4 (Tremelimumab) for three cycles of four weeks/cycle along with external beam radiation for five weeks, followed by wide surgical resection, and adjuvant Durvalumab monotherapy for four cycles. High-grade toxicity was continually assessed for the first 12 patients in phase I and the primary endpoint for phase II was an excellent histological response (grade 0 or 1 score on a semi-quantitative assessment for tumor regression). This study was registered with ClinicalTrials.gov, number NCT03116529. Findings Between October 2017 and November 2021, 23 patients were enrolled. Five patients had progression of distant disease during neoadjuvant treatment and withdrew from the study before surgery. A total of 18 patients who completed at least the neoadjuvant immunotherapy, radiation and surgery were included for analysis. The most common tumor was undifferentiated pleomorphic sarcoma (n=9, 50%). The occurrence of any adverse event (AE) was recorded in 16 (88.9%) patients, and 3 (16.7%) patients had a serious AE. Eight out of 18 patients (44.4%) had disease-free survival at a median of 39.7 months. Four out of 18 patients (22.2%) were alive-with-disease at a median of 37.1 months from diagnosis of distant metastasis, and six out of 18 (33.3%) died of disease at a median of 20.8 months from diagnosis of distant metastasis. Local recurrence occurred in two patients (11.1%) and was concomitant with distant disease in each case. Based on Response Evaluation Criteria in Solid Tumors v1.1, a partial response was noted in five (27.8%) cases, stable disease in 10 (55.6%) cases, and progressive disease in three (16.7%) cases. Histological semiquantitative analysis revealed a "good" response in eight (44.4%) patients, a "moderate" response in four (22.2%) patients, and a "poor" response in six (33.3%) patients. The mean patient-reported outcome measures regarding fatigue, physical function, or physical interference demonstrated no significant differences between various timepoints before, during, or after treatment. Conclusion Neoadjuvant combined immunotherapy and radiation for high-risk STS was relatively well-tolerated. The histological, radiologic, and clinical outcome data in this novel trial were relatively similar to historical literature for non-immunotherapy treatment regimens., Competing Interests: Human subjects: Consent for treatment and open access publication was obtained or waived by all participants in this study. University of Maryland issued approval #HM-HP-00073356-25. ClinicalTrials.gov #: NCT03116529 Eligible patients will be approached for their consent to participate. All subjects must first read, understand, and sign the IRB/REB/IEC-approved ICF before any study-specific screening procedures are performed. The subject’s clinician will be involved in the consent conversation. Patients will be informed of the study goals and data to be collected. Additionally, patients and their families will be provided with written information describing the study, the risks and benefits of participation and what will be expected of them if they choose to participate. The consent form will describe the purpose of the study, the procedures to be followed, and the risks and benefits of participation. Copies of the signed consent forms will be given to the patient, and this fact will be documented in the patient’s record. Due to the high-risk nature of this study, no proxy (LAR) consent will be obtained. Prior to initiating the consent process, the participant’s treating physician will confirm that the participant has the ability to understand the relevant study information and communicate and maintain a choice. If the physician determines that the patient lacks the capacity to consent, the patient will be declared ineligible. Recognizing that consent is an ongoing process, the study team will encourage the participants to ask additional questions that may arise during the course of their participation in the study. The research staff will endeavor to answer all questions posed by the patient and his/her family to ensure their understanding of the protocol at all times. A limited number of questions will be asked of all patients after they are introduced to the study and have reviewed the consent form. These questions assess the person’s understanding of the study and what it means to participate, their appreciation of the consequences of participation, and their ability to consider alternatives to participation. A formal comprehension test may be utilized, or comprehension will be assessed by the person(s) obtaining the consent. The patient’s physician will ask the questions and determine the appropriateness of the responses. The study will not include children or prisoners. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: This study was supported by funds through the Maryland Department of Health’s Cigarette Restitution Fund Program (CH-649-CRF) and the National Cancer Institute Cancer Center Support Grant (CCSG) P30CA134274. The immunotherapy drugs were provided by the manufacturer, AstraZeneca. . Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Ng et al.)

Study Design: Retrospective cohort study using prospectively collected data., Objective: To determine the effectiveness of intraoperative tranexamic acid (TXA) in anterior cervical discectomy and fusion (ACDF) on postoperative blood loss., Summary of Background Data: TXA has been proven to be a safe and effective agent in reducing blood loss after cervical surgery; however, its efficacy when used intraoperatively for ACDF surgeries had yet to be researched. Currently, there are few studies examining the effects of intraoperative TXA in cervical spinal fusion, and none specifically examining TXA use in ACDF., Methods: A tertiary medical center's prospectively collected spine registry was queried between 1/1/18 and 12/1/21 for all patients who underwent elective ACDF surgery and received a drain postoperatively. Patients were separated into 2 groups; those who had received intraoperative TXA and those who did not. Baseline demographic and operative variables were collected from the registry. The primary outcome was postoperative blood loss over a 24-hour period. Secondary outcomes included total drain output, intraoperative estimated blood loss, operative duration, drain duration, changes in preoperative to postoperative hemoglobin and hematocrit levels, and rate of transfusions, complications, revisions, and reoperations. Univariate and multivariate regression analyses were performed., Results: Two hundred eighty-six patients were included. One hundred ninety patients underwent ACDF and did not receive intraoperative TXA, whereas 96 patients underwent ACDF and did receive TXA. There were no differences in any demographic or baseline variables. Multivariate analysis showed intraoperative TXA was associated with shorter drain duration (β=-5.74, 95% CI: -10.9 to -0.53, P =0.031) and reduction in 24-hour drain output (β=-12.2, 95% CI: -19.4 to -4.89, P =0.001) and total drain output (β=-14.0, 95% CI: -22.9 to -5.05, P =0.002)., Conclusions: TXA use during ACDF procedures leads to a decrease in perioperative blood loss and faster drain removal. TXA is an effective and safe agent for reducing perioperative blood loss in ACDF surgery., Level of Evidence: III., Competing Interests: S.L.Z. reports being an unaffiliated neurotrauma consultant for the National Football League. B.F.S. reports being a consultant for NuVasive, Carbofix, and Depuy-Synthes, and has received institutional research support from Stryker Spine and NuVasive. A.M.A. reports receiving research support from Stryker Spine. The remaining authors declare no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Private insurers use the calendar deductible system, placing pressure on patients and medical personnel to perform medical services before the end of the year to maximize patient savings. The impact of the deductible calendar on patient-reported outcomes (PROs) after spine surgery is poorly understood. The objective of our study was to investigate if patients undergoing surgery in December had different PROs and demographics compared with all other months., Methods: The Quality Outcome Database, a national spine registry, was queried for patients who underwent elective spine surgery between January 2012 and January 2021 for degenerative spine conditions. PROs and demographics were compared between the December and non-December groups using various statistical tests., Results: A total of 978 patients (9.3%) underwent anterior cervical discectomy and fusion in December versus 9548 (90.7%) in other months. There was a significantly higher percentage of patients in December who had private insurance and were employed. A total of 1104 patients (8.5%) underwent lumbar fusion in December versus 11,826 (91.5%) in other months. There was a significantly greater chance of undergoing surgery in December if patients had private insurance and were employed. Although some PROs were statistically significant for the lumbar and cervical cohorts between December and non-December patients, none were clinically significant., Conclusions: Patients undergoing elective spine surgery in December were more likely to have private insurance and be employed. PROs for ACDF and lumbar fusions were not affected by surgical timing (December yes/no). Other spinal procedures directed at more chronic diseases might be more susceptible to external influence of insurance deductibles., (Copyright © 2022 Elsevier Inc. All rights reserved.)