National trends in the treatment of adult diffuse midline gliomas: a rare clinical scenario.

PURPOSE: Diffuse midline gliomas (DMG) include all midline gliomas with a point mutation to the histone H3 gene resulting in the substitution of a lysine with a methionine (K27M). These tumors are classified as World Health Organization grade 4 with a mean survival between 9- and 19-months following diagnosis. There is currently no standard of care for DMG, and palliative radiation therapy has been proven to only extend survival by months. Our current study aims to report current treatment trends and predictors of the overall survival of DMG. METHODS: We searched the National Cancer Database for adult patients treated for DMG from 2016 to 2020. Patients were required to have been treated with primary radiation directed at the brain with or without concurrent chemotherapy. Univariable and multivariable Cox regressions were used to determine predictors of overall survival. RESULTS: Of the 131 patients meeting the inclusion criteria, 113 (86%) received radiation and chemotherapy. Based on multivariable Cox regression, significant predictors of survival were Charlson-Deyo comorbidity index and race. Patients with a Charlson-Deyo score of 1 had 2.72 times higher odds of mortality than those with a score of 0. Patients not identifying as White or Black had 2.67 times higher odds of mortality than those identifying as White. The median survival for all patients was 19 months. CONCLUSIONS: Despite being considered ineffective, chemotherapy is still administered in most adult patients diagnosed with DMG. Significant predictors of survival were Charlson-Deyo comorbidity index and race.

Frequency and predictors of complication clustering within 30 days of spinal fusion surgery: a study of children with neuromuscular scoliosis.

PURPOSE: There is limited information on the clustering or co-occurrence of complications after spinal fusion surgery for neuromuscular disease in children. We aimed to identify the frequency and predictive factors of co-occurring perioperative complications in these children. METHODS: In this retrospective database cohort study, we identified children (ages 10-18 years) with neuromuscular scoliosis who underwent elective spinal fusion in 2012-2020 from the National Surgical Quality Improvement Program-Pediatric database. The rates of co-occurring complications within 30 days were calculated, and associated factors were identified by logistic regression analysis. Correlation between a number of complications and outcomes was assessed. RESULTS: Approximately 11% (709/6677 children with neuromuscular scoliosis undergoing spinal fusion had co-occurring complications: 7% experienced two complications and 4% experienced ≥ 3. The most common complication was bleeding/transfusion (80%), which most frequently co-occurred with pneumonia (24%) and reintubation (18%). Surgical time ≥ 400 min (odds ratio (OR) 1.49 [95% confidence interval (CI) 1.25-1.75]), fusion ≥ 13 levels (1.42 [1.13-1.79]), and pelvic fixation (OR 1.21 [1.01, 1.44]) were identified as procedural factors that independently predicted concurrent complications. Clinical risk factors for co-occurring complications included an American Society of Anesthesiologist physical status classification ≥ 3 (1.73 [1.27-2.37]), structural pulmonary/airway abnormalities (1.24 [1.01-1.52]), impaired cognitive status (1.80 [1.41-2.30]), seizure disorder (1.36 [1.12-1.67]), hematologic disorder (1.40 [1.03-1.91], preoperative nutritional support (1.34 [1.08-1.72]), and congenital malformations (1.20 [1.01-1.44]). Preoperative tracheostomy was protective against concurrent complications (0.62 [0.43-0.89]). Significant correlations were found between number of complications and length of stay, non-home discharge, readmissions, and death. CONCLUSION: Longer surgical time (≥ 400 min), fusion ≥ 13 levels and pelvic fixation are surgical risk factors independently associated with co-occurring complications, which were associated with poorer patient outcomes. Recognizing identified nonmodifiable risk factors might also be important for preoperative planning and risk stratification of children with neuromuscular scoliosis requiring spinal fusion. LEVEL OF EVIDENCE: Level IV evidence.

The 5-factor modified frailty index as a prognostic factor of stereotactic radiosurgery for metastatic disease to the brain.

OBJECTIVE: Frailty, a state of increased vulnerability to adverse health outcomes, is associated with poor neurosurgical outcomes. The relationship between frailty and stereotactic radiosurgery (SRS) for brain metastases (BMs), however, has not been adequately described. In this study, the authors attempted to examine the connection between frailty and outcomes for patients receiving SRS for BMs. METHODS: A single-center retrospective cohort study was performed. The 5-factor modified frailty index (mFI-5) was used to stratify patients into pre-frail (mFI-5 score 0-1), frail (mFI-5 score 2), and severely frail (mFI-5 score ≥ 3) cohorts at the time of SRS treatment. Both overall survival (OS) and progression-free survival (PFS) were evaluated. Factors associated with OS/PFS were assessed using Kaplan-Meier analysis and a Cox proportional hazards model. RESULTS: Two hundred three patients met the inclusion criteria and received SRS to one or more BMs. Fifty-six patients (27.6%) received SRS as an adjuvant treatment. The 12-month OS and PFS rates were 58.6% and 45.5%, respectively. One hundred twenty-six patients (62.1%) were classified as pre-frail, 58 (28.6%) as frail, and 19 (9.4%) as severely frail. Significantly less OS was demonstrated in frailer groups (frail hazard ratio [HR] 3.14, p < 0.005; severely frail HR 3.13, p < 0.005). Compared with pre-frail patients, frail patients had shorter intervals of PFS (frail HR 2.05, p < 0.005). Five patients (2.5%) had symptomatic radiation necrosis (RN) and 60 (29.6%) required repeat radiation. CONCLUSIONS: Higher frailty scores at the time of SRS treatment were predictive of shorter OS and PFS intervals.

Frequency and predictors of concurrent complications in multi-suture release for syndromic craniosynostosis.

PURPOSE: Understanding the complication profile of craniosynostosis surgery is important, yet little is known about complication co-occurrence in syndromic children after multi-suture craniosynostosis surgery. We examined concurrent perioperative complications and predictive factors in this population. METHODS: In this retrospective cohort study, children with syndromic diagnoses and multi-suture involvement who underwent craniosynostosis surgery in 2012-2020 were identified from the National Surgical Quality Improvement Program-Pediatric database. The primary outcome was concurrent complications; factors associated with concurrent complications were identified. Correlations between complications and patient outcomes were assessed. RESULTS: Among 5,848 children identified, 161 children (2.75%) had concurrent complications: 129 (2.21%) experienced two complications and 32 (0.55%) experienced ≥ 3. The most frequent complication was bleeding/transfusion (69.53%). The most common concurrent complications were transfusion/superficial infection (27.95%) and transfusion/deep incisional infection (13.04%) or transfusion/sepsis (13.04%). Two cardiac factors (major cardiac risk factors (odds ratio (OR) 3.50 [1.92-6.38]) and previous cardiac surgery (OR 4.87 [2.36-10.04])), two pulmonary factors (preoperative ventilator dependence (OR 3.27 [1.16-9.21]) and structural pulmonary/airway abnormalities (OR 2.89 [2.05-4.08])), and preoperative nutritional support (OR 4.05 [2.34-7.01]) were independently associated with concurrent complications. Children who received blood transfusion had higher odds of deep surgical site infection (OR 4.62 [1.08-19.73]; p = 0.04). CONCLUSIONS: Our results indicate that several cardiac and pulmonary risk factors, along with preoperative nutritional support, were independently associated with concurrent complications but procedural factors were not. This information can help inform presurgical counseling and preoperative risk stratification in this population.

Temporal Reinforcement of Naloxone Training Results in Significant Retention of Anti-bias and Overdose-Response Knowledge.

BACKGROUND: The opioid epidemic is an increasingly severe problem affecting public health and leading to significant economic burdens on healthcare systems. Overdose reversal training and de-stigmatization efforts are common strategies used to combat this epidemic. Nevertheless, healthcare professionals report a lack of confidence in administering naloxone and high stigmatization levels toward people with opioid use disorder (OUD). While one-time educational training reduces stigma and improves naloxone administration confidence, we previously demonstrated that knowledge retention at a three-month follow-up is reduced among a cohort of medical students. This study aimed to improve the effectiveness of opioid overdose awareness and reversal training (OOART) with a three-month follow-up abbreviated OOART (aOOART) booster video. METHODS: Voluntary OOART was offered to first-year medical students (M1) at the Drexel University College of Medicine in 2022. At this training, 82 students completed a pre-training survey to establish a baseline knowledge and attitude toward people with OUD and their familiarity with the steps to reverse an opioid overdose. Following the hour-long training, 64 of 82 (79%) participants completed the post-training survey to measure the immediate retention of training information. After 2.5 months, students were randomly selected to receive a 6.5-minute aOOART booster video or serve as an unboosted control. Students in the booster and non-booster cohorts then completed a three-month follow-up survey. RESULTS:  Students who received the aOOART booster had significantly increased opioid reversal knowledge scores compared to non-boosted control students at the three-month follow-up. The aOOART booster resulted in a retention of the lowered stigma, and participants expressed a higher willingness to respond to an opioid overdose compared to participants who did not receive the booster video at the three-month follow-up. CONCLUSIONS:  This study shows that an aOOART booster method improves knowledge retention following initial OOART. Further, the aOOART booster video served to maintain participants' reduced stigma toward people with OUD and maintained participants' willingness to respond to an opioid overdose. These results support the incorporation of an abbreviated, periodic OOART reinforcement video into opioid overdose response training nationwide. We believe this "booster video" approach is a novel and effective method to improve healthcare professionals' and medical student preparedness to render appropriate care to people with OUD.

Utilization of neoadjuvant stereotactic radiosurgery for the treatment of brain metastases requiring surgical resection: a topic review.

PURPOSE: Following surgical resection of brain metastases (BMs), adjuvant stereotactic radiosurgery (SRS) has become the standard of care post-operative cavity irradiation. Recent studies, however, have demonstrated that with the current sequence of surgery and radiation, risk of leptomeningeal disease (LMD) and radiation necrosis (RN) remains high. Pre-operative, or neoadjuvant, SRS (nSRS) has been proposed as an alternative treatment strategy which not only minimizes local recurrence (LR) but also LMD and RN. It is thought that nSRS sterilizes the tumor, allowing for minimal spillage of viable tumor cells during resection, creating less favorable conditions for LMD. Furthermore, nSRS allows for easier contouring and decreased margin irradiation during planning and treatment, respectively, diminishing the risk of symptomatic RN. While nSRS has already been adopted for treating other extra-cranial tumors, its role in treating BMs is yet to be defined. We aim to summarize recent studies in nSRS usage for BMs and the rationale of this treatment strategy. METHODS: We performed a search for articles regarding nSRS for BMs published in PubMed from 2018 to 2022 using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) method. We summarized a total of 14 retrospective reviews, case series, dose/timing studies, and ongoing Phase II & III clinical trials. CONCLUSION: In this review, we describe the findings of current studies and identify prospective clinical trials with the aim of understanding the efficacy of nSRS over current treatment standards. Herein, we also discuss the theoretical advantages and limitations of nSRS (both biologic and clinical) to help guide future clinical investigations.

Resection cavity dynamics and optimal timing of adjuvant stereotactic radiosurgery for resected brain metastases.

Purpose: Optimal timing of SRS after surgical resection of brain metastases (BMs) remains debated but is generally advocated to occur within 4 weeks of surgery to account for cavity remodeling. Our study assesses this recommendation by examining cavity dynamics and any downstream effects on outcome. Methods: Post-operative MRIs were used to compare target lesion volumes to target volume at time of SRS. Spearman's analysis identified a relationship between the time to SRS (ttSRS) and target remodeling. The Mann-Whitney-U test compared median remodeling between groups receiving standard (≤4 weeks) and late (>4 weeks) adjuvant SRS. Kaplan Meier functions estimated probabilities of local recurrence (LR) and survival (OS). A Cox proportional hazards model (CPH) identified predictors of OS, LR, and leptomeningeal disease (LMD). Results: Median ttSRS was 32 days (3-72). A positive correlation exists when comparing ttSRS to reduction in cavity volume (0-10 weeks; p = 0.01) with no difference in median cavity remodeling between standard and late SRS groups. OS and LR rates were respectively 53.3% and 70.2% at 12 months with no difference in OS (p = 0.16) or LR (p = 0.54) between standard and late SRS groups. Subtotal resection predicted LMD (HR: 6.37; p = 0.03). No grade 3 or higher toxicity was seen in follow-up. Conclusion: Resection cavities may continue to shrink well after resection. There is no significant difference in OS or LR based on ttSRS, however, treatment factors such as the extent of resection may account for outcomes such as LMD.