Practical guidance for direct oral anticoagulant use in the treatment of venous thromboembolism in primary and metastatic brain tumor patients.

Management of venous thromboembolism (VTE) in patients with primary and metastatic brain tumors (BT) is challenging because of the risk of intracranial hemorrhage (ICH). There are no prospective clinical trials evaluating safety and efficacy of direct oral anticoagulants (DOACs), specifically in patients with BT, but they are widely used for VTE in this population. A group of neuro-oncology experts convened to provide practical clinical guidance for the off-label use of DOACs in treating VTE in patients with BT. We searched PubMed for the following terms: BTs, glioma, glioblastoma (GBM), brain metastasis, VTE, heparin, low-molecular-weight heparin (LWMH), DOACs, and ICH. Although prospective clinical trials are needed, the recommendations presented aim to assist clinicians in making informed decisions regarding DOACs for VTE in patients with BT.

Patterns and predictors of anxiety and depression symptom trajectories in patients diagnosed with primary brain tumors.

BACKGROUND: Patients with primary brain tumors (pPBTs) often exhibit heightened distress. This study assesses how symptoms of anxiety and depression change over time in pPBTs and identifies factors that may predict patients' symptom trajectories. METHODS: Ninety-nine adult pPBTs completed psychosocial assessments at neuro-oncology appointments over 6-18 months. Quality of life was assessed with the Functional Assessment of Cancer Therapy-Brain; symptoms of anxiety and depression were assessed with the Patient-Reported Outcomes Measurement Information System short forms. The prevalence of patients with clinically elevated symptoms and those who experienced clinically meaningful changes in symptoms throughout follow-up were examined. Linear mixed-effects models evaluated changes in symptoms over time at the group level, and latent class growth analysis (LCGA) evaluated changes in symptoms over time at the individual level. RESULTS: At enrollment, 51.5% and 32.3% of patients exhibited clinically elevated levels of anxiety and depression, respectively. Of patients with follow-up data (n = 74), 54.1% and 50% experienced clinically meaningful increases in anxiety and depression scores, respectively. There were no significant changes in anxiety or depression scores over time, but better physical, functional, and brain-cancer well-being predicted lower levels of anxiety and depression (p < 0.001). Five sub-groups of patients with distinct symptom trajectories emerged via LCGA. CONCLUSIONS: pPBTs commonly experience elevated symptoms of anxiety and depression that may fluctuate in clinically meaningful manners throughout the disease. Routine screening for elevated symptoms is needed to capture clinically meaningful changes and identify factors affecting symptoms to intervene on.

The trial effect in patients with glioblastoma: effect of clinical trial enrollment on overall survival.

PURPOSE: To determine whether participation in a clinical trial was associated with improved survival in patients with glioblastoma (GBM). METHODS: Following IRB approval, patients were identified using CPT and ICD codes. Data was collected using retrospective review of electronic medical records. When necessary, death data was obtained from online obituaries. Inverse propensity score matching was utilized to transform the two cohorts to comparable sets. Survival was compared using Kaplan-Meyer curves and Wilcoxon Rank Sum Test. RESULTS: In this cohort of 365 patients, 89 were enrolled in a clinical trial and 276 were not. Patients enrolled in clinical trials had a significantly higher mean baseline KPS score, higher proportion of surgical resections, and were more likely to receive temozolomide treatment than patients not enrolled in a clinical trial. After inverse propensity score matching, patients enrolled in a clinical trial lived significantly longer than those not enrolled (28.8 vs 22.2 months, p = 0.005). A potential confounder of this study is that patients not in a clinical trial had significantly fewer visits with neuro-oncologists than patients enrolled in a clinical trial (7 ± 8 vs 12 ± 9, p < 0. 0001). CONCLUSIONS: Clinical trials enroll patients with the most favorable prognostic features. Even when correcting for this bias, clinical trial enrollment is an independent predictor of increased survival regardless of treatment arm.

In situ vaccination with laser interstitial thermal therapy augments immunotherapy in malignant gliomas.

INTRODUCTION: Laser interstitial thermal therapy (LITT) remains a promising advance in the treatment of primary central nervous system malignancies. As indications for its use continue to expand, there has been growing interest in its ability to induce prolonged blood brain barrier (BBB) permeability through hyperthermia, potentially increasing the effectiveness of current therapeutics including BBB-impermeant agents and immunotherapy platforms. METHODS: In this review, we highlight the mechanism of hyperthermic BBB disruption and LITT-induced immunogenic cell death in preclinical models and humans. Additionally, we summarize ongoing clinical trials evaluating a combination approach of LITT and immunotherapy, which will likely serve as the basis for future neuro-oncologic treatment paradigms. RESULTS: There is evidence to suggest a highly immunogenic response to laser interstitial thermal therapy through activation of both the innate and adaptive immune response. These mechanisms have been shown to potentiate standard methods of oncologic care. There are only a limited number of clinical trials are ongoing to evaluate the utility of LITT in combination with immunotherapy. CONCLUSION: LITT continues to be studied as a possible technique to bridge the gap between exciting preclinical results and the limited successes seen in the field of neuro-oncology. Preliminary data suggests a substantial benefit for use of LITT as a combination therapy in several clinical trials. Further investigation is required to determine whether or not this treatment paradigm can translate into long-term durable results for primary intracranial malignancies.

Role of Laser Interstitial Thermal Therapy in the Management of Primary and Metastatic Brain Tumors.

OPINION STATEMENT: Laser interstitial thermal therapy (LITT) is a minimally invasive treatment option for brain tumors including glioblastoma, other primary central nervous system (CNS) neoplasms, metastases, and radiation necrosis. LITT employs a fiber optic coupled laser delivery probe stabilized via stereotaxis to deliver thermal energy that induces coagulative necrosis in tumors to achieve effective cytoreduction. LITT complements surgical resection, radiation treatment, tumor treating fields, and systemic therapy, especially in patients who are high risk for surgical resection due to tumor location in eloquent regions or poor functional status. These factors must be balanced with the increased rate of cerebral edema post LITT compared to surgical resection. LITT has also been shown to induce transient disruption of the blood-brain barrier (BBB), especially in the peritumoral region, which allows for enhanced CNS delivery of anti-neoplastic agents, thus greatly expanding the armamentarium against brain tumors to include highly effective anti-neoplastic agents that have poor BBB penetration. In addition, hyperthermia-induced immunogenic cell death is another secondary side effect of LITT that opens up immunotherapy as an attractive adjuvant treatment for brain tumors. Numerous large studies have demonstrated the safety and efficacy of LITT against various CNS tumors and as the literature continues to grow on this novel technique so will its indications.

Tumor Treating Fields in the Management of Patients with Malignant Gliomas.

OPINION STATEMENT: Malignant gliomas remain a challenging cancer to treat due to limitations in both therapeutic and efficacious options. Tumor treating fields (TTFields) have emerged as a novel, locoregional, antineoplastic treatment modality with favorable efficacy and safety being demonstrated in the most aggressive type of malignant gliomas, glioblastoma (GBM). In 2 large randomized, controlled phase 3 trials, the addition of TTFields was associated with increased overall survival when combined with adjuvant temozolomide (TMZ) chemotherapy in patients with newly diagnosed GBM (ndGBM) and comparable overall survival compared with standard chemotherapy in patients with recurrent GBM (rGBM). TTFields target cancer cells by several mechanisms of action (MoA) including suppression of proliferation, migration and invasion, disruption of DNA repair and angiogenesis, antimitotic effects, and induction of apoptosis and immunogenic cell death. Having several MoAs makes TTFields an attractive modality to combine with standard, salvage, and novel treatment regimens (e.g., radiotherapy, chemotherapy, and immunotherapy). Treatment within the field of malignant gliomas is evolving to emphasize combinatorial approaches that work synergistically to improve patient outcomes. Here, we review the current use of TTFields in GBM, discuss MOA and treatment delivery, and consider the potential for its wider adoption in other gliomas.

Automated and Optimized Neurosurgery Scheduling System Improves Resident Satisfaction.

BACKGROUND AND OBJECTIVES: Neurosurgery residency involves a complex structure with multiple hospitals, services, and clinic days, leading to challenges in creating equitable call schedules. Manually prepared scheduling systems are prone to biases, error, and perceived unfairness. To address these issues, we developed an automated scheduling system (Automated Optimization of Neurosurgery Scheduling System [AONSS]) to reduce biases, accommodate resident requests, and optimize call variation, ultimately enhancing the educational experience by promoting diverse junior-senior-attending relationships. METHODS: AONSS was developed and tailored to the University of Florida program, with inaugural use in 2021-2022 and mandatory implementation in the 2022-2023 academic year. 2019-2021 academic years were used as control. Residents were surveyed using Google Forms before and after implementation to assess its impact. Outcome measures included call and pairing variations, duty hours, as well as subjective factors such as satisfaction, fairness, and perceived biases. RESULTS: Twenty-six residents (28%-39% female/year) were included in the study. AONSS was used for 6/13 blocks during the 2021-2022 academic year and 13/13 blocks for the 2022-2023 academic year. Overall call variation reduced by 70%. All other objective secondary measures have improved with AONSS. Weekly and monthly duty hours were reduced and less varied. Satisfaction scores improved from 21% reporting being somewhat satisfied or very satisfied to 90%. Fairness scores improved from 43% reporting being somewhat fair or very fair to 95%. Perception of gender bias decreased from 29% to 0%. No resident felt there was racial bias in either system. CONCLUSION: Our newly developed automated scheduling system effectively reduces variation among calls in a complex neurosurgery residency, which, in return, was found to increase residents' satisfaction with their schedule, improve their perception of fairness with the schedule, and has completely removed the perception of sexual bias in a program that has a large percentage of females. In addition, it was found to be associated with decreased duty hours.

The Safety and Efficacy of Concurrent Immune Checkpoint Blockade and Stereotactic Radiosurgery Therapy with Practitioner and Researcher Recommendations.

BACKGROUND: Immune checkpoint inhibitors (ICIs) have shown growing promise in the treatment of brain metastases, especially combined with stereotactic radiosurgery (SRS). The combination of ICIs with SRS has been studied for efficacy as well as increasing radiation necrosis risks. In this review, we compare clinical outcomes of radiation necrosis, intracranial control, and overall survival between patients with brain metastases treated with either SRS alone or SRS-ICI combination therapy. METHODS: A literature search of PubMed, Scopus, Embase, Web of Science, and Cochrane was performed in May 2023 for articles comparing the safety and efficacy of SRS/ICI versus SRS-alone for treating brain metastases. RESULTS: The search criteria identified 1961 articles, of which 48 met inclusion criteria. Combination therapy with SRS and ICI does not lead to significant increases in incidence of radiation necrosis either radiographically or symptomatically. Overall, no difference was found in intracranial control between SRS-alone and SRS-ICI combination therapy. Combination therapy is associated with increased median overall survival. Notably, some comparative studies observed decreased neurologic deaths, challenging presumptions that improved survival is due to greater systemic control. The literature supports SRS-ICI administration within 4 weeks of another for survival but remains inconclusive, requiring further study for other outcome measures. CONCLUSIONS: Combination SRS-ICI therapy is associated with significant overall survival benefit for patients with brain metastases without significantly increasing radiation necrosis risks compared to SRS alone. Although intracranial control rates appear to be similar between the 2 groups, timing of treatment delivery may improve control rates and demands further study attention.

Advancements in chimeric antigen receptor-expressing T-cell therapy for glioblastoma multiforme: Literature review and future directions.

Glioblastoma multiforme (GBM) is an aggressive cancer that has been difficult to treat and often requires multimodal therapy consisting of surgery, radiotherapy, and chemotherapy. Chimeric antigen receptor-expressing (CAR-T) cells have been efficacious in treating hematological malignancies, resulting in several FDA-approved therapies. CAR-T cells have been more recently studied for the treatment of GBM, with some promising preclinical and clinical results. The purpose of this literature review is to highlight the commonly targeted antigens, results of clinical trials, novel modifications, and potential solutions for challenges that exist for CAR-T cells to become more widely implemented and effective in eradicating GBM.

Developing a computable phenotype for glioblastoma.

BACKGROUND: Glioblastoma is the most common malignant brain tumor, and thus it is important to be able to identify patients with this diagnosis for population studies. However, this can be challenging as diagnostic codes are nonspecific. The aim of this study was to create a computable phenotype (CP) for glioblastoma multiforme (GBM) from structured and unstructured data to identify patients with this condition in a large electronic health record (EHR). METHODS: We used the University of Florida (UF) Health Integrated Data Repository, a centralized clinical data warehouse that stores clinical and research data from various sources within the UF Health system, including the EHR system. We performed multiple iterations to refine the GBM-relevant diagnosis codes, procedure codes, medication codes, and keywords through manual chart review of patient data. We then evaluated the performances of various possible proposed CPs constructed from the relevant codes and keywords. RESULTS: We underwent six rounds of manual chart reviews to refine the CP elements. The final CP algorithm for identifying GBM patients was selected based on the best F1-score. Overall, the CP rule "if the patient had at least 1 relevant diagnosis code and at least 1 relevant keyword" demonstrated the highest F1-score using both structured and unstructured data. Thus, it was selected as the best-performing CP rule. CONCLUSIONS: We developed and validated a CP algorithm for identifying patients with GBM using both structured and unstructured EHR data from a large tertiary care center. The final algorithm achieved an F1-score of 0.817, indicating a high performance, which minimizes possible biases from misclassification errors.

Academic accomplishments of Black neurosurgeons in the United States.

OBJECTIVE: Neurosurgery has remained relatively homogeneous in terms of racial and gender diversity, trailing behind national demographics. Less than 5% of practicing neurosurgeons in the United States identify as Black/African American (AA). Research and academic productivity are highly emphasized within the field and are crucial for career advancement at academic institutions. They also serve as important avenues for mentorship and recruitment of diverse trainees and medical students. This study aimed to summarize the academic accomplishments of AA neurosurgeons by assessing publication quantity, h-index, and federal grant funding. METHODS: One hundred thirteen neurosurgery residency training programs accredited by the Accreditation Council for Graduate Medical Education in 2022 were included in this study. The American Society of Black Neurosurgeons registry was reviewed to analyze the academic metrics of self-identified Black or AA academic neurosurgeons. Data on the academic rank, leadership position, publication quantity, h-index, and race of neurosurgical faculty in the US were obtained from publicly available information and program websites. RESULTS: Fifty-five AA and 1393 non-AA neurosurgeons were identified. Sixty percent of AA neurosurgeons were fewer than 10 years out from residency training, compared to 37.4% of non-AA neurosurgeons (p = 0.001). AA neurosurgeons had a median 32 (IQR 9, 85) publications compared to 52 (IQR 22, 122) for non-AA neurosurgeons (p = 0.019). AA neurosurgeons had a median h-index of 12 (IQR 5, 24) compared to 16 (IQR 9, 31) for non-AA colleagues (p = 0.02). Following stratification by academic rank, these trends did not persist. No statistically significant differences in the median amounts of awarded National Institutes of Health funding (p = 0.194) or level of professorship attained (p = 0.07) were observed between the two cohorts. CONCLUSIONS: Racial disparities between AA and non-AA neurosurgeons exist in publication quantity and h-index overall but not when these groups are stratified by academic rank. Given that AA neurosurgeons comprise more junior faculty, it is expected that their academic accomplishments will increase as more enter academic practice and current neurosurgeons advance into more senior positions.

Discontinuation of Antiseizure Medications in Patients With Brain Tumors.

Patients with brain tumors will experience seizures during their disease course. While providers can use antiseizure medications to control these events, patients with brain tumors can experience side effects, ranging from mild to severe, from these medications. Providers in subspecialties such as neurology, neuro-oncology, neurosurgery, radiation oncology, and medical oncology often work with patients with brain tumor to balance seizure control and the adverse toxicity of antiseizure medications. In this study, we sought to explore the problem of brain tumor-related seizures/epilepsy in the context of how and when to consider antiseizure medication discontinuation. Moreover, we thoroughly evaluate the literature on antiseizure medication discontinuation for adult and pediatric patients and highlight recommendations relevant to patients with both brain tumors and seizures.

Duration of Prophylactic Levetiracetam After Surgery for Brain Tumor: A Prospective Randomized Trial.

BACKGROUND: Levetiracetam is commonly used as a prophylactic antiseizure medication in patients undergoing surgical resection of brain tumors. OBJECTIVE: To quantitate side effects experienced in patients treated with 1 week vs 6 weeks of prophylactic levetiracetam using validated measures for neurotoxicity and depression. METHODS: Patients undergoing surgical resection of a supratentorial tumor with no seizure history were randomized within 48 hours of surgery to receive prophylactic levetiracetam for the duration of either 1 or 6 weeks. Patients were given oral levetiracetam extended release 1000 mg during the first part of this study. Owing to drug backorder, patients enrolled later in this study received levetiracetam 500 mg BID. The primary outcome was the change in the neurotoxicity score 6 weeks after drug initiation. The secondary outcome was seizure incidence. RESULTS: A total of 81 patients were enrolled and randomized to 1 week (40 patients) or 6 weeks (41 patients) of prophylactic levetiracetam treatment. The neurotoxicity score slightly improved in the overall cohort between baseline and reassessment. There was no significant difference between groups in neurotoxicity or depression scores. Seizure incidence was low in the entire cohort of patients with 1 patient in each arm experiencing a seizure during the follow-up period. CONCLUSION: The use of prophylactic levetiracetam did not result in significant neurotoxicity or depression when given for either 1 week or 6 weeks. The incidence of seizure after craniotomy for tumor resection is low regardless of duration of therapy.

Evaluation of patients referred to the spine clinic via telemedicine and the impact on diagnosis and surgical decision-making.

OBJECTIVE: Telemedicine encounters are expanding in utility for outpatient care and evaluation, partially as a necessity during the COVID-19 pandemic. It is unclear if telemedicine evaluation is comparable to in-person assessment of patients with spinal pathology undergoing surgical consultation. The objective of this study was to determine if treatment plans change for spine patients evaluated in person following an initial telemedicine consultation. METHODS: Patients referred to the authors' comprehensive spine center were evaluated first via telemedicine and then in clinic. Telemedicine evaluations were conducted via video evaluation with an attending surgeon. Demographic data including age, gender, and distance traveled from the clinic were retrospectively recorded. A chart review retrieved symptoms, radiographic details, and past medical history. The primary outcome was if the treatment plan changed (plan change [PC]) after seeing the patient in the clinic. Chi-square tests and binary logistical regression produced uni- and multivariate analyses. RESULTS: There were 152 new patients seen via telemedicine and in person. Pathology was present in the cervical (28.3%), thoracic (9.9%), and lumbar (61.8%) spine. The most common symptom was pain (72.4%), followed by radiculopathy (66.4%), weakness (26.3%), myelopathy (15.1%), and claudication (12.5%). There were 37 patients (24.3%) for whom there was a PC after clinic evaluation, and of those, only 5 (3.3%) were due to physical examination (PCPE) findings. On univariate analysis, a longer duration between telemedicine and clinic visit (odds ratio [OR] 1.094 per 7 days, p = 0.003), having pathology in the thoracic spine (OR 3.963, p = 0.018) and lack of sufficient imaging (OR 25.455, p < 0.0001) were predictive of a PC. Having pathology in the cervical spine (OR 9.538, p = 0.047) and adjacent-segment disease (OR 11.471, p = 0.010) were predictive of a PCPE. CONCLUSIONS: This study demonstrates that telemedicine may be an effective modality for the initial evaluation of spine surgical patients, without compromising decision-making in the absence of an in-person physical examination.

Clinical management of seizures in patients with meningiomas: Efficacy of surgical resection for seizure control and patient-tailored postoperative anti-epileptic drug management.

Meningiomas are the most common primary intracranial tumor. They are slow growing and often incidentally found tumors that arise from the arachnoid villi. As they grow, they have a greater likelihood of becoming symptomatic with seizures being one of the most clinically significant symptoms. Seizures are more likely to present as a symptom of larger meningiomas and meningiomas that compress cortical areas particularly those in non-skull base locations. These seizures are often managed medically, utilizing the same anti-seizure medications that are used to treat other causes of epilepsy. We discuss common anti-seizure medications used including valproate, phenobarbital, carbamazepine, phenytoin, lacosamide, lamotrigine, levetiracetam and topiramate and their common adverse effects. The goal of pharmacotherapy for seizure control is to maximize seizure control while minimizing the adverse effects of the medication. The decision to provide medical management is dependent on individual seizure history and plans for surgical treatment. Patients who did not require seizure prophylaxis before surgery are commonly prescribed seizure prophylaxis postoperatively. Symptomatic meningiomas not controlled by medical management alone are commonly evaluated for surgical resection. The efficacy of surgical resection in providing seizure freedom is dependent on several features of the tumor including tumor size, the extent of the peritumoral edema, the number of tumors, sinus infiltration and the degree of resection.

The Enhanced Recovery After Surgery pathway for posterior cervical surgery: a retrospective propensity-matched cohort study.

OBJECTIVE: The Enhanced Recovery After Surgery (ERAS) protocol is a comprehensive, multifaceted approach aimed at improving postoperative outcomes. It incorporates a range of strategies to promote early and more effective recovery, including reducing pain, complications, and length of stay, without increasing readmission rate. To date, ERAS for spine surgery patients has been primarily limited to lumbar surgery and anterior cervical decompression and fusion (ACDF). ERAS has not been previously studied for posterior cervical surgery, which may present a greater opportunity for improvement in patient outcomes with ERAS than ACDF. This single-institution, multi-surgeon study assessed the impact of an ERAS protocol in patients undergoing posterior cervical decompression surgery. METHODS: This study included a retrospective consecutive patient cohort with controls that were propensity matched for age, body mass index, sex, home opioid use, surgical levels, Nurick grade, and smoking status. In addition, consecutive patients who underwent posterior cervical decompression surgery for degenerative disease from December 2014 to December 2021 were included. ERAS was implemented in December 2018. Demographic, perioperative, clinical, and radiographic information was gathered. Regression models were created to evaluate length of stay, physiological function, pain levels, and opioid use. The primary focus was length of stay, with secondary outcomes including timing of ambulation, bowel movement, and voiding; daily pain scores; opioid consumption; discharge status; 30-day readmission rates; and reoperation rates. RESULTS: There were 366 patients included in the study, all of whom were included in multivariate models, and 254 (127 in each cohort) were included on the basis of matching. After propensity matching, patient characteristics, operative procedures, and operative duration were similar between groups. The ERAS cohort had a significantly improved length of stay (3.2 vs 4.7 days, p < 0.0001) and home discharge rate (80% vs 50%, p < 0.001) without an increase in readmission rate. The ERAS cohort had an earlier day of the first ambulation (p = 0.003), bowel movement (p = 0.014), and voiding (p = 0.001). ERAS demonstrated a significantly lower composite complication rate (1.1 vs 1.8, p < 0.0001). ERAS resulted in better maximum pain scores (p = 0.043) and trended toward improved mean pain scores (p = 0.072), although total opioid use was similar. CONCLUSIONS: Implementing a novel ERAS protocol significantly improved length of stay, return of physiological function, home discharge, complications, and maximum pain score after posterior cervical surgery.

Contemporary RNA Therapeutics for Glioblastoma.

Glioblastoma (GBM) is the most common primary brain tumor in adults and is universally lethal with a median survival of less than two years with standard therapy. RNA-based immunotherapies have significant potential to establish a durable treatment response for malignant brain tumors including GBM. RNA offers clear advantages over antigen-focused approaches but cannot often be directly administered due to biological instability. This review will focus on utilization of RNA dendritic cell vaccines and RNA nanoparticle therapies in the treatment of GBM. RNA-pulsed dendritic cell vaccines have been shown to be safe in a small phase I clinical trial and RNA-loaded nanoparticle vaccines will soon be underway in GBM patients (NCT04573140).

Glioma Immunotherapy: Advances and Challenges for Spinal Cord Gliomas.

Spinal cord gliomas are rare entities that often have limited surgical options. Immunotherapy has shown promise in intracranial gliomas with some research suggesting benefit for spinal cord gliomas. A focused review of immunotherapies that have been investigated in spinal cord gliomas was performed. The primary methods of immunotherapy investigated in spinal cord gliomas include immune checkpoint inhibitors, adoptive T-cell therapies, and vaccine strategies. There are innumerable challenges that must be overcome to effectively apply immunotherapeutic strategies to the spinal cord gliomas including low incidence, few antigenic targets, the blood spinal cord barrier, the immunosuppressive tumor microenvironment and neurotoxic treatment effects. Nonetheless, research has suggested ways to overcome these challenges and treatments have been effective in case reports for metastatic non-small cell lung cancer, melanoma, midline glioma and glioblastoma. Current therapies for spinal cord gliomas are markedly limited. Further research is needed to determine if the success of immunotherapy for intracranial gliomas can be effectively applied to these unique tumors.

Enhanced recovery after surgery (ERAS) improves return of physiological function in frail patients undergoing one- to two-level TLIFs: an observational retrospective cohort study.

BACKGROUND CONTEXT: The enhanced recovery after surgery (ERAS) protocol is a multimodal approach which has been shown to facilitate recovery of physiological function, and reduce early post-operative pain, complications, and length of stay (LOS) in open one- to two-level TLIF. The benefit of ERAS in specifically frail patients undergoing TLIF has not been demonstrated. Frailty is clinically defined as a syndrome of physiological decline that can predispose patients undergoing surgery to poor outcomes. PURPOSE: This study primarily evaluated the benefit of an ERAS protocol in frail patients undergoing one- or two-level open TLIF compared to frail patients without ERAS. Secondarily, we assessed whether outcomes in frail patients with ERAS approximated those seen in nonfrail patients with ERAS. STUDY DESIGN: Retrospective consecutive patient cohort with controls propensity-matched for age, body mass index, sex, and smoking status. PATIENT SAMPLE: Consecutive patients that underwent one- or two-level open TLIF for degenerative disease from August, 2015 to July, 2021 by a single surgeon. ERAS was implemented in December 2018. OUTCOME MEASURES: Primary outcome measure was return of postoperative physiological function defined as the summation of first day to ambulate, first day to bowel movement, and first day to void. Additional outcome measures included LOS, daily average pain scores, opioid use, discharge disposition, 30-day readmission rate, and reoperation. METHODS: A retrospective analysis of frail patients > 65 years of age undergoing one- to two-level open TLIF post-ERAS were compared to propensity matched frail pre-ERAS patients. Frailty was assessed using the Fried phenotype classification (score >1). Patient demographics, LOS, first-day-to-ambulate (A1), first-day-to-bowel movement (B1), first-day-to-void (V1) were collected. Return of physiological function was defined as A1+B1+V1. Primary analysis was a comparison of frail patients pre-ERAS versus post-ERAS to determine effect of ERAS on return of physiologic function with frailty. Secondary analysis was a comparison of post-ERAS frail versus post-ERAS nonfrail patients to determine if return of physiologic function in frail patients with ERAS approximates that of nonfrail patients. RESULTS: In the primary analysis, 32 frail patients were included with mean age ± standard deviation of 72.8±4.4 years, mean BMI 28.8±5.5, 65.6% were male, 15 pre-ERAS and 17 post-ERAS. Patient characteristics were similar between groups. After ERAS implementation, return of physiological function improved by a mean 3.2 days overall (post-ERAS 3.4 vs. pre-ERAS 6.7 days) (p<.0001), indicating a positive effect of ERAS in frail patients. Additionally, length of stay improved by 1 day (4.8±1.6 vs. 3.8±1.9 days, p<.0001). Total daily intravenous morphine milligram equivalent (MME) as well as average daily pain scores were similar between groups. Secondarily, 26 nonfrail patients post ERAS were used as a comparison group with the 17 post-ERAS frail cohort. Mean age of this cohort was 73.4±4.6 years, mean BMI 27.4±4.9, and 61.9% were male. Return of physiologic function was similar between cohorts (post-ERAS nonfrail 3.5 vs. post-ERAS frail 3.4 days) (p=.938), indicating the benefit with ERAS in frail patients approximates that of nonfrail patients. CONCLUSIONS: ERAS significantly improves return of physiologic function and length of stay in patients with frailty after one- to two-level TLIF, and approximates improved outcomes seen in non-frail patients.

Histologic Findings at the Time of Repeat Resection Predicts Survival in Patients with Glioblastoma.

OBJECTIVE: Radiographic worsening in patients with glioblastoma undergoing treatment may be due to tumor recurrence or treatment effect. The overall prognosis of these patients based on histologic findings at the time of repeat resection is not well established. METHODS: Patients with glioblastoma at our institution were identified. Patients who only had 1 surgery were excluded. Demographic and clinical data were recorded. The histologic diagnosis at the time of repeat surgery was recorded as either tumor recurrence or pseudoprogression. For this study, pseudoprogression was defined as absence of tumor histologic features and could show coagulative necrosis, reactive gliosis, and/or inflammatory infiltration. RESULTS: A total of 115 patients were identified, 106 with tumor recurrence and 9 with pseudoprogression. The pseudoprogression group had a greater percentage of patients with O6-methylguanine DNA-methyltransferase (MGMT) methylation (37.7% vs. 66.7%), but these results did not reach statistical significance. The overall median survival was 23.1 months. The overall median survival was 22.0 months in the tumor recurrence group and 33.3 months in the pseudoprogression group (P = 0.0814). The overall median survival from the time of repeat surgery was 8.4 months for the entire cohort, 8.3 months for the tumor recurrence group and 18.4 months for the pseudoprogression group (P = 0.0063). In multivariable analysis, presence of tumor features was predictive of worse overall survival from the time of second surgery (hazards ratio 3.96, 95% confidence interval: 1.30-12.06, P = 0.0156). CONCLUSIONS: In patients with worsening imaging, the absence of tumor on histologic diagnosis is associated with improved survival from the time of second surgery.