Association of CDKN2A alterations with increased postoperative seizure risk after resection of brain metastases.

OBJECTIVE: Seizures are common and significantly disabling for patients with brain metastases (BMs). Although resection can provide seizure control, a subset of patients with BMs may continue to suffer seizures postoperatively. Genomic BM characteristics may influence which patients are at risk for postoperative seizures. This work explores correlations between genomic alterations and risk of postoperative seizures following BM resection. METHODS: All patients underwent BM resection at a single institution, with available clinical and sequencing data on more than 500 oncogenes. Clinical seizures were documented pre- and postoperatively. A random forest machine learning classification was used to determine candidate genomic alterations associated with postoperative seizures, and clinical and top genomic variables were correlated with postoperative seizures by using Cox proportional hazards models. RESULTS: There were 112 patients with BMs who underwent 114 surgeries and had at least 1 month of postoperative follow-up. Seizures occurred preoperatively in 26 (22.8%) patients and postoperatively in 25 (21.9%). The Engel classification achieved at 6 months for those with preoperative seizures was class I in 13 (50%); class II in 6 (23.1%); class III in 5 (19.2%), and class IV in 2 (7.7%). In those with postoperative seizures, only 8 (32.0%) had seizures preoperatively, and preoperative seizures were not a significant predictor of postoperative seizures (HR 1.84; 95% CI 0.79-4.37; p = 0.156). On random forest classification and multivariate Cox analysis controlling for factors including recurrence, extent of resection, and number of BMs, CDKN2A alterations were associated with postoperative seizures (HR 3.22; 95% CI 1.27-8.16; p = 0.014). Melanoma BMs were associated with higher risk of postoperative seizures compared with all other primary malignancies (HR 5.23; 95% CI 1.37-19.98; p = 0.016). Of 39 BMs with CDKN2A alteration, 35.9% (14/39) had postoperative seizures, compared to 14.7% (11/75) without CDKN2A alteration. The overall rate of postoperative seizures in melanoma BMs was 42.9% (15/35), compared with 12.7% (10/79) for all other primary malignancies. CONCLUSIONS: CDKN2A alterations and melanoma primary malignancy are associated with increased postoperative seizure risk following resection of BMs. These results may help guide postoperative seizure prophylaxis in patients undergoing resection of BMs.

Genomic alterations associated with rapid progression of brain metastases.

OBJECTIVE: The aim of this study was to investigate associations between genomic alterations in resected brain metastases and rapid local and distant CNS recurrence identified at the time of postoperative adjuvant radiosurgery. METHODS: This was a retrospective study on patients who underwent resection of intracranial brain metastases. Next-generation sequencing of more than 500 coding genes was performed on brain metastasis specimens. Postoperative and preradiosurgery MR images were compared to identify rapid recurrence. Genomic data were associated with rapid local and distant CNS recurrence of brain metastases using nominal regression analyses. RESULTS: The cohort contained 92 patients with 92 brain metastases. Thirteen (14.1%) patients had a rapid local recurrence, and 64 (69.6%) patients had rapid distant CNS progression by the time of postoperative adjuvant radiosurgery, which occurred in a median time of 25 days (range 3-85 days) from surgery. RB1 and CTNNB1 mutations were seen in 8.7% and 9.8% of the cohort, respectively, and were associated with a significantly higher risk of rapid local recurrence (RB1: OR 13.6, 95% CI 2.0-92.39, p = 0.008; and CTNNB1: OR 11.97, 95% CI 2.25-63.78, p = 0.004) on multivariate analysis. No genes were found to be associated with rapid distant CNS progression. However, the presence of extracranial disease was significantly associated with a higher risk of rapid distant recurrence on multivariate analysis (OR 4.06, 95% CI 1.08-15.34, p = 0.039). CONCLUSIONS: Genomic alterations in RB1 or CTNNB1 were associated with a significantly higher risk of rapid recurrence at the resection site. Although no genomic alterations were associated with rapid distant recurrence, having active extracranial disease was a risk factor for new lesions by the time of adjuvant radiotherapy after resection.

Perioperative Outcomes of Open Anterior Vertebral Body Tethering and Instrumented Posterior Spinal Fusion for Skeletally Immature Patients With Idiopathic Scoliosis.

BACKGROUND: Correcting adolescent idiopathic scoliosis (AIS) without fusion can be achieved with anterior vertebral body tethering (AVBT). However, little is known about the perioperative outcomes, pain control, and clinical outcomes in patients undergoing AVBT compared with instrumented posterior spinal fusion (IPSF). METHODS: In this retrospective cohort study, we compared pediatric patients with AIS who underwent either AVBT or IPSF. Inclusion criteria were based on the AVBT group, which included primary thoracic idiopathic scoliosis, Risser ≤1, curve magnitude 40 to 70 degrees, age 9 to 15, no prior spine surgery, index surgery between 2014 and 2019, and minimum 2-year follow-up. Patient demographics, perioperative metrics, pain visual analog scale scores, opiate morphine equivalent usage, cost data, and radiographic outcomes were compared. RESULTS: We identified 23 patients who underwent AVBT and 24 matched patients in the IPSF group based on inclusion criteria. Patients undergoing AVBT and PSF were similar in age (12±1 y vs. 13±1 y, P =0.132) and average follow-up time (3.8±1.6 y vs. 3.3±1.4 y, P =0.210). There were 23 female patients (87%) in the AVBT group and 24 female (92%) patients in the IPSF group. Intraoperatively, estimated blood loss (498±290 vs. 120±47 mL, P <0.001) and procedure duration (419±95 vs. 331±83 min, P =0.001) was significantly greater in the IPSF group compared with AVBT. Length of stay was lower in the AVBT group compared with PSF (4±1 vs. 5±2 d, P =0.04). PSF patients had significantly greater total postoperative opiate morphine equivalent use compared with AVBT (2.2±1.9 vs. 5.6±3.4 mg/kg, P <0.001). Overall direct costs following PSF and AVBT were similar ($47,655+$12,028 vs. $50,891±$24,531, P =0.58). Preoperative radiographic parameters were similar between both the groups, with a major thoracic curve at 51±10 degrees for AVBT and 54±9 degrees for IPSF ( P =0.214). At the most recent follow-up, IPSF patients had greater curve reduction to a mean major thoracic curve of 11±7 degrees (79%) compared with 19±10 degrees (63%) in AVBT patients ( P =0.002). Nine patients (39%) required revision surgery following AVBT compared with 4 patients(17%) following IPSF ( P =0.09). CONCLUSIONS: In a select cohort of patients, AVBT offers decreased surgical time, blood loss, length of stay, and postoperative opiate usage compared with IPSF. Although IPSF resulted in greater deformity correction at 2-year follow-up, the majority of patients who underwent AVBT had ≤35 major curves and avoided fusion. There is optimism for AVBT as a treatment option for select AIS patients, but long-term complications are still being understood, and the risk for revision surgeries remains high. LEVEL OF EVIDENCE: Level III.

Prevalence and Predictors of Stroke in Patients with Crohn's Disease: A Nationwide Study.

OBJECTIVES: Mounting evidence points to the microbiome as a susceptibility factor for neurological disorders. Patients with Crohn's disease (CD) are at higher ischemic stroke (IS) risk, but no large scale epidemiologic studies have identified risk factors for stroke in this population. MATERIALS AND METHODS: We analyzed the 2017 Nationwide Inpatient Sample (NIS) dataset to identify patients with a discharge diagnosis of Crohn's disease using the International Classification of Diseases, 10th Revision, Clinical Modification (ICD-10-CM) code K50.X. We identified patients with a primary/secondary discharge diagnosis of IS using ICD-10-CM code I63.X. We compared sociodemographic and clinical variables between stroke and non-stroke patients with CD. Logistic regression analysis was applied to identify factors associated with IS. RESULTS: Of 30,212 patients with CD, 369 (1.2 %) had a discharge diagnosis of IS. Older age (odds ratio [OR], 1.03 [95% CI, 1.02-1.04], top quartile income (OR, 1.58 [95% CI, 1.10-2.30]), and hospitalization in a South Atlantic (OR, 1.82 [95% CI, 1.11-3.14]), East South Central (OR, 2.30 [95% CI, 1.28-4.25]), or West South Central hospital (OR, 2.40 [95% CI, 1.39-4.28]) were independently associated with IS. Clinical variables independently associated with IS in patients with CD included: atrial fibrillation (OR, 1.66 [95% CI, 1.15-2.33]), atherosclerosis (OR, 2.41 [95% CI, 1.32-4.10]), hyperlipidemia (OR, 1.69 [95% CI, 1.33-2.15]), hypertension (OR, 1.53 [95% CI, 1.18-1.98]) and valvular disease (OR, 1.62 [95% CI, 1.01-2.48). CONCLUSION: A subset of traditional stroke risk factors are associated with IS in patients with CD. CD patients with these conditions could be targeted for vascular risk reduction and surveillance.

Toward the elimination of hepatitis C in the United States.

The emergence of effective direct-acting antiviral (DAA) agents has reignited discussion over the potential for hepatitis C elimination in the United States. Eliminating hepatitis C will require a critical examination of technical feasibility, economic considerations, and social/political attention. Tremendous advancement has been made with the availability of sensitive diagnostic tests and highly effective DAAs capable of achieving sustained viral response (SVR) in more than 95% of patients. Eliminating hepatitis C also requires escalating existing surveillance networks to monitor for new epidemics. All preventive interventions such as clean syringe and needle exchange programs, safe injection sites, opioid substitution therapies, and mental health services need to be expanded. Although costs of DAAs have raised budget concerns for hepatitis C elimination, studies have shown that eliminating hepatitis C will produce a savings of up to 6.5 billion USD annually along with other intangible benefits such as increased work productivity and quality of life. Economic models and meta-analyses strongly suggest universal hepatitis C screening for all adults rather than just for birth cohort and high-risk populations. Social and political factors are at least as important as technical feasibility and economic considerations. Due to lack of promotion and public awareness, HCV elimination efforts continue to receive inadequate funding. Social stigma continues to impede meaningful policy changes. Eliminating hepatitis C is an attainable public health goal that will require intense collaboration and sustained public support. (Hepatology 2018;67:2449-2459).

Pretransplant Sarcopenia in Patients With NASH Cirrhosis Does Not Impact Rehospitalization or Mortality.

BACKGROUND: Malnutrition and muscle wasting are common in patients with end-stage liver disease (ESLD), yet go underdiagnosed. Frequently used indices of nutritional status, such as body mass index, are inflated in patients with ESLD due to a fluid overloaded state. Previous work has demonstrated a strong association between psoas muscle area, a surrogate for sarcopenia, and worse survival following liver transplantation; however, the impact of sarcopenia on post liver transplant outcomes in patients with nonalcoholic steatohepatitis (NASH) cirrhosis has not been evaluated. GOALS: Describe the impact of sarcopenia in patients with NASH cirrhosis on post liver transplantation outcomes, including initial hospital length of stay, rehospitalization, and survival. MATERIALS AND METHODS: A single-center, retrospective analysis was conducted of adult liver transplants performed for NASH cirrhosis between 2002 and 2015. Sarcopenia was defined by psoas area measured at the L3 vertebra from abdominal imaging within 6 months before orthotopic liver transplant (OLT). RESULTS: A total of 146 patients were evaluated. The mean Model for End-Stage Liver Disease score at transplant was 34.9±7.4. Sarcopenia was present in 62% of patients and was more likely in female and Hispanic patients. There were no significant differences in length of initial hospitalization following OLT, days hospitalized within the first year post-OLT, survival at 1 year, or overall survival between sarcopenic and nonsarcopenic patients. CONCLUSIONS: Sarcopenia in patients with NASH cirrhosis and high Model for End-Stage Liver Disease scores is not associated with an increase in mortality or rehospitalization following liver transplantation; however, the study findings were limited by a small sample size.

Presumed Consent: A Potential Tool for Countries Experiencing an Organ Donation Crisis.

BACKGROUND: There is currently an inadequate supply of allografts to meet the number of transplant candidates worldwide. A number of controversial policies, including implementation of a presumed consent organ donation system, have been considered to rectify the organ donation crisis. AIMS: A secondary retrospective data analysis aimed to assess the impact of switching to a presumed consent organ donation model on organ donation rates. METHODS: Deceased organ donation rates were compared before and after countries adopted presumed consent. RESULTS: Six countries met entry criteria. All six countries had an increase in liver donation rates, while 4 out of the six countries had an increase in kidney donation rates. The overall mean (± SD) liver donation rate was 3.23 (± 0.97) per million population (pmp) before the transition and 6.46 (± 1.81) pmp after the transition (p < 0.0001). The overall mean (± SD) kidney donation rate was 17.94 (± 3.34) pmp before the transition and 26.58 (± 4.23) pmp after the transition (p < 0.0001). The percentage increase in liver and kidney donation rates varied among countries, ranging from 28 to 1186%. CONCLUSION: The transition from explicit to presumed consent was associated with a significant increase in liver donation rates in all countries that met our criteria, while the effect on kidney donation rates was partially realized. Although presumed consent alone is unlikely to explain the increase in donation rates, the adoption of such a policy may prove to be a worthwhile risk for countries experiencing consistently low organ donation rates.

Use of hepatitis C-positive grafts in hepatitis C-negative liver transplant recipients is cost effective.

BACKGROUND: The number of patients needing liver transplantation (LT) exceeds the number of available allografts. The current opioid epidemic in this country has increased the number of potential donors infected with hepatitis C (HCV). METHODS: We assessed the incremental cost-effectiveness ratio (ICER) by comparing the costs and number of liver transplants performed using HCV-positive and HCV-negative grafts into patients without HCV infection in a decision analysis model with a 1-year time horizon. RESULTS: The use of HCV-positive grafts was found to have an ICER below $50 000 across all MELD scores. Using our baseline cohort with a model for end-stage liver disease (MELD) score of 15-22, the ICER was $21 233/additional LT performed. As the MELD scores increased, the ICER decreased. Above a MELD score of 23, the use of HCV-positive grafts became cost saving (-$115 419). Our model was robust to all variables tested in the sensitivity analyses, except drug costs. CONCLUSION: The results of our decision analysis model highlight the potential pharmacoeconomic benefit of utilizing HCV-positive grafts in LT candidates who are not infected with HCV. The use of HCV-positive grafts is at least cost effective and even cost saving in patients with MELD scores above 23.

Correlation of Brain Metastasis Genomic Alterations with Preoperative Imaging Features.

BACKGROUND: The aim of this study was to examine associations between genomic alterations in brain metastases and common preoperative imaging findings including overt intratumoral hemorrhage, cystic features, and edema. METHODS: A single-center, retrospective study was performed including patients who underwent surgical resection of brain metastasis with available preoperative magnetic resonance imaging (MRI). Next-generation sequencing of more than 500 coding genes was performed on the resected brain metastases. Preoperative MRI was reviewed to identify the presence of intratumoral hemorrhage, cystic features, and edema in the resected brain metastasis. Genomic data were then correlated with the imaging features using univariate and multivariate nominal logistic regression analyses. RESULTS: We included 144 brain metastases from 141 patients in the study cohort. Half (72) of the metastases had an intratumoral hemorrhage, 26 (18%) had cystic features, and 130 (90%) had edema. Mutations in TP53 were associated with a reduced risk of intratumoral hemorrhage (odds ratio [OR] 0.2, 95% confidence interval [CI] 0.07-0.5, P < 0.001). Mutations in RB1 and CCND1 were associated with elevated risk of the metastasis having cystic features (OR 10.3, 95% CI 2.0-52.6, P = 0.005, OR 18.4, 95% CI 2.2-155.3, P = 0.008, respectively). PIK3CA mutations were associated with a reduced risk of peritumoral edema (OR 0.2, 95% CI 0.04-0.8, P = 0.03). CONCLUSIONS: Several genomic alterations in brain metastases are associated with MRI features including hemorrhage, cystic features, and edema. These results provide insight into tumor biology and patients at risk of developing these imaging features.

Genomic alterations associated with postoperative nodular leptomeningeal disease after resection of brain metastases.

OBJECTIVE: The relationship between brain metastasis resection and risk of nodular leptomeningeal disease (nLMD) is unclear. This study examined genomic alterations found in brain metastases with the aim of identifying alterations associated with postoperative nLMD in the context of clinical and treatment factors. METHODS: A retrospective, single-center study was conducted on patients who underwent resection of brain metastases between 2014 and 2022 and had clinical and genomic data available. Postoperative nLMD was the primary endpoint of interest. Targeted next-generation sequencing of > 500 oncogenes was performed in brain metastases. Cox proportional hazards analyses were performed to identify clinical features and genomic alterations associated with nLMD. RESULTS: The cohort comprised 101 patients with tumors originating from multiple cancer types. There were 15 patients with nLMD (14.9% of the cohort) with a median time from surgery to nLMD diagnosis of 8.2 months. Two supervised machine learning algorithms consistently identified CDKN2A/B codeletion and ERBB2 amplification as the top predictors associated with postoperative nLMD across all cancer types. In a multivariate Cox proportional hazards analysis including clinical factors and genomic alterations observed in the cohort, tumor volume (× 10 cm3; HR 1.2, 95% CI 1.01-1.5; p = 0.04), CDKN2A/B codeletion (HR 5.3, 95% CI 1.7-16.9; p = 0.004), and ERBB2 amplification (HR 3.9, 95% CI 1.1-14.4; p = 0.04) were associated with a decreased time to postoperative nLMD. CONCLUSIONS: In addition to increased resected tumor volume, ERBB2 amplification and CDKN2A/B deletion were independently associated with an increased risk of postoperative nLMD across multiple cancer types. Additional work is needed to determine if targeted therapy decreases this risk in the postoperative setting.

Prevalence of Social Needs & Social Risks Among EMS Providers.

Background: A national shortage of Emergency Medical Service (EMS) providers is a critical issue for the profession that has only worsened during the COVID-19 pandemic. Researchers have identified possible causes, including difficult workplace conditions, low wages, and burnout. However, the impact of EMS providers' social needs and social risks has yet to be thoroughly explored. Methods: Demographic data for 1,112 EMS providers who responded to the 2021 national Social Needs in the Pre-hospital Setting (SNIPS) Study were analyzed to produce descriptive statistics and test for differences in social needs using chi square tests. Results: EMS providers reported experiencing housing insecurity (23.0%), food insecurity (27.4%), struggles with substance use (20.9%), mental health concerns (41.5%), domestic violence (18.5%), and healthcare affordability concerns (30.8%) during their EMS career. Almost 90% of study participants screened positive for burnout. Both women and emergency medical technicians (EMTs) were more likely than men and paramedics respectively to suffer from food and housing insecurity, mental health issues, and domestic violence at some point in their careers. Discussion: EMS providers reported high levels of burnout as well as a variety of social needs. Social needs may necessitate overtime work, increasing risk of burnout and negatively impacting providers' well-being and contributing to the provider shortage. Barriers to entry for paramedic training and gender differences in promotion rates may exacerbate the disparities experienced by EMTs and female providers, respectively. Conclusion: With high levels of burnout, staffing shortages, and EMS professionals leaving the profession, more must be done to support EMS providers. This includes programs to facilitate entry to and advancement within the EMS profession, ability to make ends meet without reliance on overtime pay, and mental health support.

Radiographic and perioperative outcomes following anterior thoracic vertebral body tethering and posterior lumbar spine tethering: a pilot series.

BACKGROUND AND CONTEXT:  In patients with adolescent idiopathic scoliosis (AIS) of main thoracic and lumbar spine regions, combined anterior thoracic vertebral body tethering and posterior lumbar spine tethering (ATVBT/PLST) is a novel non-fusion treatment option for growth modulation and conservation of motion. METHODS:  Fourteen patients with AIS who underwent ATVBT/PLST with at least 2-year follow-up were included. Primary outcomes included quality of life as assessed by SRS-22 instruments, radiographic analysis, and revision operations. We secondarily reported perioperative metrics and post-operative opiate morphine equivalents (OME). Clinical success was defined as patients who achieved skeletal maturity with ≤ 30° curve magnitude of both their main thoracic and thoracolumbar/lumbar curves and who did not undergo posterior spine instrumentation and fusion (PSIF). RESULTS: Patients had a mean age of 11.6 years (range 10-14 years), majority were girls (92%), and mean follow-up was 3.0 years (range 2-4.8 years). All patients were skeletally immature with a Risser ≤ 2. Included curves were Lenke 1C, 3C, or 6C. Mean preoperative curve magnitudes were 53° ± 8° (range 45°-65°) main thoracic and 49° ± 9° (range 40°-62°) thoracolumbar/lumbar curves. At most recent follow-up, patients had a mean main thoracic curve of 29° ± 8° (range 15°-40°) and a mean thoracolumbar/lumbar curve of 20° ± 15° (range 4°-35°). 50% required a revision operation. Cable breakage occurred in 43%, which did not always require revision. One patient progressed to thoracic fusion, but no patient underwent lumbar fusion. Patients had a mean SRS-22 outcome score of 4.2 ± 0.4. CONCLUSIONS: ATVBT/PLST is a potential alternative to spine fusion for select immature patients with AIS at a minimum 2-year follow-up. ATVBT/PLST potentially offers motion conservation at the cost of a higher revision rate. Further study and reporting of results are necessary to refine indications and techniques, which in turn will improve outcomes of this procedure. LEVEL OF EVIDENCE: Level IV-Case series without comparative group.

Combined Anterior Thoracic Vertebral Body Tethering and Posterior Lumbar Tethering Results in Quicker Return to Sport and Activity Compared to Posterior Spinal Instrumented Fusion in Patients with Adolescent Idiopathic Scoliosis.

STUDY DESIGN: Retrospective comparative study. OBJECTIVE: To compare patient-reported physical activity between anterior thoracic vertebral body tethering and posterior lumbar spine tethering (ATVBT/PLST) and posterior spinal instrumentation and fusion (PSIF) with minimum 2 year follow-up. METHODS: Consecutive skeletally immature patients with idiopathic scoliosis and a thoracic and lumbar curve magnitude ≥40° who underwent either ATVBT/PLST or PSIF from 2015-2019 were included. The primary outcome was rate of returning to sport. Secondary outcomes included ability to bend and satisfaction with sport performance as well as weeks until return to sport, school, physical education (PE) classes, and running. RESULTS: Ten patients underwent ATVBT/PLST and 12 underwent PSIF. ATVBT/PLST patients reported significantly faster return to sport (13.5 weeks vs 27.9 weeks, P = .04), running (13.3 weeks vs 28.8 weeks, P = .02), and PE class (12.6 weeks vs 26.2 weeks, P = .04) compared to PSIF patients. ATVBT/PLST patients reported that they had to give up activities due to their ability to bend at lower rates than PSIF patients while reporting "no changes" in their ability to bend after surgery at higher rates than PSIF patients (0% vs 4% giving up activities and 70% vs 0% reporting no changes in bending ability for ATVBT/PLST and PSIF, respectively, P = .01). Compared to PSIF patients, ATVBT/PLST patients experienced less main thoracic and thoracolumbar/lumbar curve correction at most recent follow-up (thoracic: 41 ± 19% vs 69 ± 18%, P = .001; thoracolumbar/lumbar: 59 ± 25% vs 78 ± 15%, P = .02). No significant differences in the number of revision surgeries were observed between ATVBT/PLST and PSIF patients (4 (40%) and 1 (8%) for ATVBT/PLST and PSIF, respectively, P = .221). CONCLUSIONS: ATVBT/PLST patients reported significantly faster rates of returning to sport, running, and PE. In addition, ATVBT/PLST patients were less likely to have to give up activities due to bending ability after surgery and reported no changes in their ability to bend after surgery more frequently than PSIF patients. However, the overall rate of return to the same or higher level of sport participation was high amongst both groups, with no significant difference observed between ATVBT/PLST and PSIF patients.

Supervised machine learning algorithms demonstrate proliferation index correlates with long-term recurrence after complete resection of WHO grade I meningioma.

OBJECTIVE: Meningiomas are the most common primary intracranial tumor, and resection is a mainstay of treatment. It is unclear what duration of imaging follow-up is reasonable for WHO grade I meningiomas undergoing complete resection. This study examined recurrence rates, timing of recurrence, and risk factors for recurrence in patients undergoing a complete resection (as defined by both postoperative MRI and intraoperative impression) of WHO grade I meningiomas. METHODS: The authors conducted a retrospective, single-center study examining recurrence risk for adult patients with a single intracranial meningioma that underwent complete resection. Uni- and multivariate nominal logistic regression and Cox proportional hazards analyses were performed to identify variables associated with recurrence and time to recurrence. Two supervised machine learning algorithms were then implemented to confirm factors within the cohort that were associated with recurrence. RESULTS: The cohort consisted of 823 patients who met inclusion criteria, and 56 patients (6.8%) had recurrence on imaging follow-up. The median age of the cohort was 56 years, and 77.4% of patients were female. The median duration of head imaging follow-up for the entire cohort was 2.7 years, but for the subgroup of patients who had a recurrence, the median follow-up was 10.1 years. Estimated 1-, 5-, 10-, and 15-year recurrence-free survival rates were 99.8% (95% confidence interval [CI] 98.8%-99.9%), 91.0% (95% CI 87.7%-93.6%), 83.6% (95% CI 78.6%-87.6%), and 77.3% (95% CI 69.7%-83.4%), respectively, for the entire cohort. On multivariate analysis, MIB-1 index (odds ratio [OR] per 1% increase: 1.34, 95% CI 1.13-1.58, p = 0.0003) and follow-up duration (OR per year: 1.12, 95% CI 1.03-1.21, p = 0.012) were both associated with recurrence. Gradient-boosted decision tree and random forest analyses both identified MIB-1 index as the main factor associated with recurrence, aside from length of imaging follow-up. For tumors with an MIB-1 index < 8, recurrences were documented up to 8 years after surgery. For tumors with an MIB-1 index ≥ 8, recurrences were documented up to 12 years following surgery. CONCLUSIONS: Long-term imaging follow-up is important even after a complete resection of a meningioma. Higher MIB-1 labeling index is associated with greater risk of recurrence. Imaging screening for at least 8 years in patients with an MIB-1 index < 8 and at least 12 years for those with an MIB-1 index ≥ 8 may be needed to detect long-term recurrences.

Factors associated with preoperative and postoperative seizures in patients undergoing resection of brain metastases.

OBJECTIVE: Epileptic seizures are a common and potentially devastating complication of metastatic brain tumors. Although tumor-related seizures have been described in previous case series, most studies have focused on primary brain tumors and have not differentiated between different types of cerebral metastases. The authors analyzed a large surgical cohort of patients with brain metastases to examine risk factors associated with preoperative and postoperative seizures and to better understand the seizure risk factors of metastatic brain tumors. METHODS: Patients who underwent resection of a brain metastasis at the University of California, San Francisco (UCSF), were retrospectively reviewed. Patients included in the study were ≥ 18 years of age, required resection of a brain metastasis, and were treated at UCSF. Primary cancers included melanoma, non-small cell lung adenocarcinoma, breast adenocarcinoma, colorectal adenocarcinoma, esophageal adenocarcinoma, gastric adenocarcinoma, renal cell carcinoma, urothelial carcinoma, ovarian carcinoma, cervical squamous cell carcinoma, and endometrial adenocarcinoma. Patients were evaluated for primary cancer type and seizure occurrence, as well as need for use of antiepileptic drugs preoperatively, at time of discharge, and at 6 months postoperatively. Additionally, Engel classification scores were assigned to those patients who initially presented with seizures preoperatively. Univariate and multivariate regression analyses were used to assess the association of tumor type with preoperative seizures. RESULTS: Data were retrospectively analyzed for 348 consecutive patients who underwent surgical treatment of brain metastases between 1998 and 2019. The cohort had a mean age of 60 years at the time of surgery and was 59% female. The mean and median follow-up durations after the date of surgery for the cohort were 22 months and 10.8 months, respectively. In univariate analysis, frontal lobe location (p = 0.05), melanoma (p = 0.02), KRAS mutation in lung carcinoma (p = 0.04), intratumoral hemorrhage (p = 0.04), and prior radiotherapy (p = 0.04) were associated with seizure presentation. Postoperative checkpoint inhibitor use (p = 0.002), prior radiotherapy (p = 0.05), older age (p = 0.002), distant CNS progression (p = 0.004), and parietal lobe tumor location (p = 0.002) were associated with seizures at 6 months postoperatively. The final multivariate model confirmed the independent effects of tumor location in the frontal lobe and presence of intratumoral hemorrhage as predictors of preoperative seizures, and checkpoint inhibitor use and parietal lobe location were identified as significant predictors of seizures at 6 months postoperatively. CONCLUSIONS: Within this surgical cohort of patients with brain metastases, seizures were seen in almost a quarter of patients preoperatively. Frontal lobe metastases and hemorrhagic tumors were associated with higher risk of preoperative seizures, whereas checkpoint inhibitor use and parietal lobe tumors appeared to be associated with seizures at 6 months postoperatively. Future research should focus on the effect of metastatic lesion-targeting therapeutic interventions on seizure control in these patients.

Identification of risk factors associated with leptomeningeal disease after resection of brain metastases.

OBJECTIVE: Resection of brain metastases (BMs) may be associated with increased risk of leptomeningeal disease (LMD). This study examined rates and predictors of LMD, including imaging subtypes, in patients who underwent resection of a BM followed by postoperative radiation. METHODS: A retrospective, single-center study was conducted examining overall LMD, classic LMD (cLMD), and nodular LMD (nLMD) risk. Logistic regression, Cox proportional hazards, and random forest analyses were performed to identify risk factors associated with LMD. RESULTS: Of the 217 patients in the cohort, 47 (21.7%) developed postoperative LMD, with 19 cases (8.8%) of cLMD and 28 cases (12.9%) of nLMD. Six-, 12-, and 24-month LMD-free survival rates were 92.3%, 85.6%, and 71.4%, respectively. Patients with cLMD had worse survival outcomes from the date of LMD diagnosis compared with nLMD (median 2.4 vs 6.9 months, p = 0.02, log-rank test). Cox proportional hazards analysis identified cerebellar/insular/occipital location (hazard ratio [HR] 3.25, 95% confidence interval [CI] 1.73-6.11, p = 0.0003), absence of extracranial disease (HR 2.49, 95% CI 1.27-4.88, p = 0.008), and ventricle contact (HR 2.82, 95% CI 1.5-5.3, p = 0.001) to be associated with postoperative LMD. A predictive model using random forest analysis with an area under the receiver operating characteristic curve of 0.87 in a test cohort identified tumor location, systemic disease status, and tumor volume as the most important factors associated with LMD. CONCLUSIONS: Tumor location, absence of extracranial disease at the time of surgery, ventricle contact, and increased tumor volume were associated with LMD. Further work is needed to determine whether escalating therapies in patients at risk of LMD prevents disease dissemination.

CDKN2A/B co-deletion is associated with increased risk of local and distant intracranial recurrence after surgical resection of brain metastases.

Background: While genetic alterations in brain metastases (BMs) have been previously explored, there are limited data examining their association with recurrence after surgical resection. This study aimed to identify genetic alterations within BMs associated with CNS recurrence after surgery across multiple cancer types. Methods: A retrospective, single-center study was conducted with patients who underwent resection of a BM with available clinical and gene sequencing data available. Local and remote CNS recurrence were the primary study outcomes. Next-generation sequencing of the coding regions in over 500 oncogenes was performed in brain metastasis specimens. Cox proportional hazards analyses were performed to identify clinical features and genomic alterations associated with CNS recurrence. Results: A total of 90 patients undergoing resection of 91 BMs composed the cohort. Genes most frequently mutated in the cohort included TP53 (64%), CDKN2A (37%), TERT (29%), CDKN2B (23%), NF1 (14%), KRAS (14%), and PTEN (13%), all of which occurred across multiple cancer types. CDKN2A/B co-deletion was seen in 21 (23.1%) brain metastases across multiple cancer types. In multivariate Cox proportional hazard analyses including patient, tumor, and treatment factors, CDKN2A/B co-deletion in the brain metastasis was associated with increased risk of local (HR 4.07, 95% CI 1.32-12.54, P = 0.014) and remote (HR 2.28, 95% CI 1.11-4.69, P = 0.025) CNS progression. Median survival and length of follow-up were not different based on CDKN2A/B mutation status. Conclusions: CDKN2A/B co-deletion detected in BMs is associated with increased CNS recurrence after surgical resection. Additional work is needed to determine whether more aggressive treatment in patients with this mutation may improve outcomes.

Comparison of 90-day complications and two-year reoperation rates between anterior and posterior interbody fusion for single-level degenerative spondylolisthesis.

Background: For the surgical treatment of single-level degenerative spondylolisthesis (DS), patients can be treated with either an anterior or posterior interbody fusion. Prior studies have shown that patients with symptomatic degenerative spondylolisthesis treated surgically maintain substantially greater pain relief and improvement in function when compared to those treated non-operatively, but no consensus has emerged between which approach results in the best outcomes. Methods: The PearlDiver MARINER database was queried for patients with single-level DS who underwent either an anterior or posterior lumbar interbody fusion. Both populations were compared on multiple outcomes, including reoperation, post-operative complications, and readmission rates at 90 days, as well as rates of reoperation and cauda equina syndrome two-years postoperatively. Results: At 90 days patients who underwent anterior interbody were found to have higher rates of DVT (OR 2.53, 95% CI 1.74 - 3.70, p<0.001), ileus (OR 1.43, 95% CI 1.25 - 1.64, p<0.001), and readmission (OR 1.28, 95% CI 1.19 - 1.38, p<0.001). Patients who underwent posterior interbody fusion were found to have higher rates of revision procedures (OR 0.63, 95% CI 0.59 - 0.66, p<0.001), transfusion (OR 0.68, 95% CI 0.58 - 0.78, p<0.001), acute kidney injury (OR 0.84, 95% CI 0.75 - 0.95, p=0.0046), and cauda equina syndrome (OR 0.53, 95% CI 0.40 - 0.69, p<0.001). At 2 years, patients who underwent posterior fusion required revision procedures (OR 0.70, 95% CI 0.67 - 0.74, p<0.001) and developed cauda equina syndrome (OR 0.62, 95% CI 0.50 - 0.77, p<0.001) at a higher rate than those who underwent anterior fusion. Conclusions: Patients who underwent anterior interbody fusion for treatment of degenerative spondylolisthesis were found to have increased rates of DVT, ileus, and were more likely to be readmitted to the hospital within 90 days, while patients who underwent posterior interbody fusion were found to have higher rates of reoperation, transfusion, AKI, and cauda equina syndrome. Increased rates of reoperation and development of cauda equina in the posterior fusion group persisted at 2 years post-operatively.

Radial Forearm Free Flap Reconstruction of Glossectomy Defects Without Tracheostomy.

OBJECTIVES: To assess the feasibility of radial forearm free flap (RFFF) reconstruction of glossectomy defects without tracheostomy tube (TT). METHODS: Retrospective review of patients with at least oral tongue defects who underwent RFFF reconstruction. Pre- and intra-operative factors were documented. Post-operative respiratory complications included inability to extubate, pneumonia, or need for re-intubation or TT within 30 days. RESULTS: Twenty-one patients underwent RFFF reconstruction without TT, and 36 patients with TT. The average hospital length of stay was 1.5 days shorter in those without TT (P < .01). Two patients who underwent TT placement experienced a respiratory complication (P = .27). There were no respiratory complications among those without TT. After multivariate analyses, large tongue base defect (>25% resection, P < .001) and bilateral neck dissection (P < .001) were independently associated with TT placement. CONCLUSIONS: In our experience, RFFF reconstruction of glossectomy defects is feasible without TT among selected patients with small tongue base defects (≤25% resection) and unilateral neck dissection.

Salvage Surgery for Local Control of Brain Metastases After Previous Stereotactic Radiosurgery: A Single-Center Series.

BACKGROUND: Although overall survival (OS) has improved in patients with brain metastases (BMs), control of recurrent BMs remains a therapeutic challenge. Salvage surgery may achieve acceptable control rates in the setting of progression after previous stereotactic radiosurgery (SRS), yet it remains a question how additional adjuvant therapies may affect outcomes and how patient selection for salvage surgery may be optimized. METHODS: Patients receiving salvage surgery for BM progression after previous SRS were retrospectively reviewed from a single center. Outcomes of interest included local tumor progression, leptomeningeal dissemination, and OS. Cox proportional hazard models and nominal logistic regression were applied to determine factors associated with outcomes of interest. RESULTS: A total of 43 patients with 50 BMs were included. After salvage surgery, local progression was observed for 17 BMs (34%), leptomeningeal dissemination was observed in 17 patients (39.5%), and censored median OS was 17.9 months. On multivariate analysis, use of brachytherapy was associated with improved local control (hazard ratio [HR], 0.15; 95% confidence interval [CI], 0.04-0.6; P = 0.008). For patients treated with SRS ≥4.5 months before salvage surgery, both brachytherapy (HR, 0.07; 95% CI, 0.01-0.39; P = 0.002) and postoperative adjuvant SRS (HR, 0.14; 95% CI, 0.02-1.00; P = 0.05) were associated with improved local control compared with no adjuvant radiation therapy. Presence of extracranial malignancy (HR, 6.70; 95% CI, 2.58-17.42; P < 0.0001) was associated with shorter survival. Graded prognostic assessment underestimated survival in 79.1% of patients, with a mean difference of 18.9 months between graded prognostic assessment-estimated and actual OS. CONCLUSIONS: In properly selected patients, salvage surgery may be an appropriate therapy for BM progression after previous SRS. Adjuvant brachytherapy and repeat SRS can offer significant benefit for local control with salvage resection.