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Background Enhanced recovery after surgery (ERAS) programs are a model of care that aim to improve patient outcomes, reduce complications, and facilitate recovery while reducing healthcare-associated costs and admission length. While such programs have been developed in other surgical subspecialties, there have yet to be guidelines published specifically for laser interstitial thermal therapy (LITT). Here we describe the first multidisciplinary ERAS preliminary protocol for LITT for the treatment of brain tumors. Methods Between the years 2013 and 2021, 184 adult patients consecutively treated with LITT at our single institution were retrospectively analyzed. During this time, a series of pre, intra, and postoperative adjustments were made to the admission course and surgical/anesthesia workflow with the goal of improving recovery and admission length. Results The mean age at surgery was 60.7 years with a median preoperative Karnofsky performance score of 90 ± 13. Lesions were most commonly metastases (50%) and high-grade gliomas (37%). The mean length of stay was 2.4 days, with the average patient being discharged 1.2 days after surgery. There was an overall readmission rate of 8.7% with a LITT-specific readmission rate of 2.2%. Three of 184 patients required repeat intervention in the perioperative period, and there was one perioperative mortality. Conclusions This preliminary study shows the proposed LITT ERAS protocol to be a safe means of discharging patients on postoperative day 1 while preserving outcomes. Although future prospective work is needed to validate this protocol, results show the ERAS approach to be promising for LITT.

Background There is a need to evaluate the outcomes of patients who underwent brain tumor surgery with subsequent telemedicine or in-person follow-up during the COVID-19 pandemic. Methods We retrospectively included all patients who underwent surgery for brain tumor resection by a single neurosurgeon at our Institution from the beginning of the COVID-19 pandemic restrictions (March 2020) to August 2021. Outcomes were assessed by stratifying the patients using their preference for follow-up method (telemedicine or in-person). Results Three-hundred and eighteen (318) brain tumor patients who were included. The follow-up method of choice was telemedicine (TM) in 185 patients (58.17%), and in-person (IP) consults in 133 patients. We found that patients followed by TM lived significantly farther, with a median of 36.34 miles, compared to a median of 22.23 miles in the IP cohort (P = .0025). We found no statistical difference between the TM and the IP group, when comparing visits to the emergency department (ED) within 30 days after surgery (7.3% vs 6.01%, P = .72). Readmission rates, wound infections, and 30-day mortality were similar in both cohorts. These findings were also consistent after matching cohorts using a propensity score. The percentage of telemedicine follow-up consults was higher in the first semester (73.17%) of the COVID-19 pandemic, compared to the second (46.21%), and third semesters (47.86%). Conclusions Telehealth follow-up alternatives may be safely offered to patients after brain tumor surgery, thereby reducing patient burden in those with longer distances to the hospital or special situations as the COVID-19 pandemic.

Background Large-scale brain networks and higher cognitive functions are frequently altered in neuro-oncology patients, but comprehensive non-invasive brain mapping is difficult to achieve in the clinical setting. The objective of our study is to evaluate traditional and non-traditional eloquent areas in brain tumor patients using a machine-learning platform. Methods We retrospectively included patients who underwent surgery for brain tumor resection at our Institution. Preoperative MRI with T1-weighted and DTI sequences were uploaded into the Quicktome platform. We categorized the integrity of nine large-scale brain networks: language, sensorimotor, visual, ventral attention, central executive, default mode, dorsal attention, salience and limbic. Network integrity was correlated with preoperative clinical data. Results One-hundred patients were included in the study. The most affected network was the central executive network (49%), followed by the default mode network (43%) and dorsal attention network (32%). Patients with preoperative deficits showed a significantly higher number of altered networks before the surgery (3.42 vs 2.19, P < .001), compared to patients without deficits. Furthermore, we found that patients without neurologic deficits had an average 2.19 networks affected and 1.51 networks at-risk, with most of them being related to non-traditional eloquent areas (P < .001). Conclusion Our results show that large-scale brain networks are frequently affected in patients with brain tumors, even when presenting without evident neurologic deficits. In our study, the most commonly affected brain networks were related to non-traditional eloquent areas. Integrating non-invasive brain mapping machine-learning techniques into the clinical setting may help elucidate how to preserve higher-order cognitive functions associated with those networks.

Background Poor prognosis of glioblastoma patients and the extensive heterogeneity of glioblastoma at both the molecular and cellular level necessitates developing novel individualized treatment modalities via genomics-driven approaches. Methods This study leverages numerous pharmacogenomic and tissue databases to examine drug repositioning for glioblastoma. RNA-seq of glioblastoma tumor samples from The Cancer Genome Atlas (TCGA, n = 117) were compared to “normal” frontal lobe samples from Genotype-Tissue Expression Portal (GTEX, n = 120) to find differentially expressed genes (DEGs). Using compound gene expression data and drug activity data from the Library of Integrated Network-Based Cellular Signatures (LINCS, n = 66,512 compounds) CCLE (71 glioma cell lines), and Chemical European Molecular Biology Laboratory (ChEMBL) platforms, we employed a summarized reversal gene expression metric (sRGES) to “reverse” the resultant disease signature for GBM and its subtypes. A multiparametric strategy was employed to stratify compounds capable of blood-brain barrier penetrance with a favorable pharmacokinetic profile (CNS-MPO). Results Significant correlations were identified between sRGES and drug efficacy in GBM cell lines in both ChEMBL(r = 0.37, P < .001) and Cancer Therapeutic Response Portal (CTRP) databases (r = 0.35, P < 0.001). Our multiparametric algorithm identified two classes of drugs with highest sRGES and CNS-MPO: HDAC inhibitors (vorinostat and entinostat) and topoisomerase inhibitors suitable for drug repurposing. Conclusions Our studies suggest that reversal of glioblastoma disease signature correlates with drug potency for various GBM subtypes. This multiparametric approach may set the foundation for an early-phase personalized -omics clinical trial for glioblastoma by effectively identifying drugs that are capable of reversing the disease signature and have favorable pharmacokinetic and safety profiles.

Background The incidence of symptomatic radiation necrosis (RN) has risen as radiotherapy is increasingly used to control brain tumor progression. Traditionally managed with steroids, symptomatic RN can remain refractory to medical treatment, requiring surgical intervention for control. The purpose of our study was to assess a single institution’s experience with craniotomy for steroid-refractory pure RN. Methods The medical records of all tumor patients who underwent craniotomies at our institution from 2011 to 2016 were retrospectively reviewed for a history of preoperative radiotherapy or radiosurgery. RN was confirmed histopathologically and patients with active tumor were excluded. Preoperative, intraoperative, and outcome information was collected. Primary outcomes measured were postoperative KPS and time to steroid freedom. Results Twenty-four patients with symptomatic RN were identified. Gross total resection was achieved for all patients. Patients with metastases experienced an increase in KPS (80 vs 100, P < .001) and required a shortened course of dexamethasone vs patients with high-grade gliomas (3.4 vs 22.2 weeks, P = .003). RN control and neurological improvement at 13.3 months’ follow-up were 100% and 66.7%, respectively. Adrenal insufficiency after rapidly tapering dexamethasone was the only morbidity (n = 1). Overall survival was 93.3% (14/15) at 1 year. Conclusion In cases of treatment-refractory symptomatic RN, resection can lead to an overall improvement in postoperative health status and neurological outcomes with minimal RN recurrence. Craniotomy for surgically accessible RN can safely manage symptomatic patients, and future studies assessing the efficacy of resection vs bevacizumab may be warranted.

BACKGROUND Evolving requirements for patient and physician safety and rapid regulatory changes have stimulated interest in neurosurgical telemedicine in the COVID-19 era. OBJECTIVE To conduct a systematic literature review investigating treatment of neurosurgical patients via telemedicine, and to evaluate barriers and challenges. Additionally, we review recent regulatory changes that affect telemedicine in neurosurgery, and our institution's initial experience. METHODS A systematic review was performed including all studies investigating success regarding treatment of neurosurgical patients via telemedicine. We reviewed our department's outpatient clinic billing records after telemedicine was implemented from 3/23/2020 to 4/6/2020 and reviewed modifier 95 inclusion to determine the number of face-to-face and telemedicine visits, as well as breakdown of weekly telemedicine clinic visits by subspecialty. RESULTS A total of 52 studies (25 prospective and 27 retrospective) with 45 801 patients were analyzed. A total of 13 studies were conducted in the United States and 39 in foreign countries. Patient management was successful via telemedicine in 99.6% of cases. Telemedicine visits failed in 162 cases, 81.5% of which were due to technology failure, and 18.5% of which were due to patients requiring further face-to-face evaluation or treatment. A total of 16 studies compared telemedicine encounters to alternative patient encounter mediums; telemedicine was equivalent or superior in 15 studies. From 3/23/2020 to 4/6/2020, our department had 122 telemedicine visits (65.9%) and 63 face-to-face visits (34.1%). About 94.3% of telemedicine visits were billed using face-to-face procedural codes. CONCLUSION Neurosurgical telemedicine encounters appear promising in resource-scarce times, such as during global pandemics.

BACKGROUND Tumors of the posterior pituitary are a distinct group of low-grade neoplasms arising from the sellar region. According to the most recent World Health Organization (WHO) guidelines, these tumors are grouped based on TTF-1 immunostain positivity. The coexistence of a posterior and anterior pituitary tumors is statistically extremely unlikely. OBJECTIVE In this study, we present a case of a 41-year-old woman suffering from Cushing syndrome with the presence of two pituitary masses on MRI. Also, the relevant literature is systematically reviewed. METHODS Two databases (PubMed and Google Scholar) and crossed references were systematically reviewed for TTF-1 pituitary tumors with coexisting pituitary adenoma or increased pituitary serum hormone levels. A literature review was performed according to PRISMA guidelines. Also, one patient from our institution is reported. Data regarding demographic features, type of anterior and posterior pituitary tumor, clinical features of the patients and lab results, MRI findings, and pathology results were extracted. RESULTS Seventeen retrospective case reports and case series were identified and included. Twenty-four patients were analyzed (including the reported case). The mean age was 46 ± 16 years, with a male-to-female ratio of 0.33:1. Pituicytomas and granular cell tumors were the only posterior pituitary tumors reported in 19 (79%) and 5 (21%) cases, respectively. There are only eight cases reported (including our patient) with a confirmed pituitary adenoma and a TTF-1 pituitary tumor (one GCT with GH-secreting adenoma, five pituicytoma with ACTH-secreting adenoma, one with GH-secreting adenoma and one with a null type adenoma). CONCLUSION We presented the eighth reported case of a TTF-1 pituitary tumor coexisting with a pituitary adenoma. We think that improving the amount of the tissue specimen available for pathology evaluation could increase the incidence of these very rare tumors.

INTRODUCTION: Laser interstitial thermal therapy (LITT) is a novel, minimally-invasive adjuvant therapy that is well-suited for intracranial tumors in deep or critical areas, recurrences failing standard therapy, and poor open-surgical candidates. To better characterize safety and clinical outcomes, we present the largest single-institutional experience with LITT for recurrent brain metastases. METHODS: All patients undergoing LITT for single recurrent brain metastases from 2013–2018 at the University of Miami were included in this study. Primary outcomes included extent of ablation (EOA), time-to-recurrence (TTR), and overall survival (OS). Secondary endpoints include neurologic status and complication rate. Kaplan-Meier survival analysis was performed to quantify TTR and OS, compare outcomes by primary tumor of origin, and identify potential predictors of TTR and OS. RESULTS: Thirty-six patients underwent 44 LITT procedures; all had undergone prior treatment with stereotactic radiosurgery (SRS). Mean age was 56.8 years and 83.3% were female. Average pretreatment tumor volume was 6.6cm3. Patients were treated with a mean ablation dose of 12.4W (9.8-14W), achieving a median EOA of 100% (range 55–100%). At median follow-up of 11.6 months (IQR 4.6–19.1 months), 34 of 44 (87.3%) cases had tumor control on radiographic imaging and 22 of 36 (61.1%) of patients remain alive. Median TTR was 55.9 months; median OS was 25.5 months. Neither TTR nor OR differed significantly by primary tumor of origin (P >.05). EOA >88% predicted longer TTR (P=.01) Neurologic status was stable or improved in all surviving patients. No major complications occurred (0% rate). CONCLUSIONS: Our institutional experience demonstrates LITT is safe for intracranial metastases resistant to SRS and offers several advantages over open surgical treatment. TTR and OS were not associated with primary tumor of origin. A threshold EOA >88% predicted longer TTR. Randomized studies are needed to evaluate the role of LITT as a treatment adjunct.

Aims: Research into the relationship between pathogens, faecal indicator microbes and environmental factors in beach sand has been limited, yet vital to the understanding of the microbial relationship between sand and the water column and to the improvement of criteria for better human health protection at beaches. The objectives of this study were to evaluate the presence and distribution of pathogens in various zones of beach sand (subtidal, intertidal and supratidal) and to assess their relationship with environmental parameters and indicator microbes at a non-point source subtropical marine beach. Methods and Results: In this exploratory study in subtropical Miami (Florida, USA), beach sand samples were collected and analysed over the course of 6 days for several pathogens, microbial source tracking markers and indicator microbes. An inverse correlation between moisture content and most indicator microbes was found. Significant associations were identified between some indicator microbes and pathogens (such as nematode larvae and yeasts in the genus Candida), which are from classes of microbes that are rarely evaluated in the context of recreational beach use. Conclusions: Results indicate that indicator microbes may predict the presence of some of the pathogens, in particular helminthes, yeasts and the bacterial pathogen Staphylococcus aureus including methicillin-resistant forms. Indicator microbes may thus be useful for monitoring beach sand and water quality at non-point source beaches. Significance and Impact of the Study: The presence of both indicator microbes and pathogens in beach sand provides one possible explanation for human health effects reported at non-point sources beaches.

Aims The aim of this study was to determine the effect of blood pressure (BP) on platelet nitric oxide (NO) signalling and on formation of circulating monocyte-platelet aggregates (MPA), as well as the role of platelet NO in modulating MPA in hypertension. Methods and results We first examined platelet NO signalling in 23 untreated hypertensive (UH) and 23 normotensive (NT) subjects. Platelets from hypertensives exhibited reduced NO synthase activation by albuterol or collagen, as well as suppressed basal and stimulated NO-attributable cyclic guanosine-3′,5′-monophosphate, compared with NT. In a second study, comprising 106 subjects with a wide BP range, circulating MPA showed a strong positive correlation with BP. On multiple regression analysis, using a model incorporating systolic BP (SBP), diastolic BP, age, lipids, gender, and smoking status, the only independent predictor of MPA was SBP. Nitric oxide synthase inhibition with N G-monomethyl-l-arginine increased MPA in NT but not in hypertensives, whereas the NO donor spermine NONOate (SNO) decreased MPA in NT but not in hypertensives. Platelet P-selectin expression was higher in hypertensives than in NT, and its expression was suppressed by SNO in NT only. Conclusion Platelet NO production and responsiveness are suppressed with raised BP, and this may contribute to the increase in platelet P-selectin and hence in circulating MPA in hypertension.

Objective: Ageing is associated with an increase in atherothrombotic disease. Platelet-derived nitric oxide (NO) inhibits platelet activation, but the effect of age on platelet NO signaling is unknown. We investigated platelet NO biosynthesis and responsiveness in older (N45 years old) as compared with younger (b30 years old) healthy human subjects. Methods: Platelet NO synthase (NOS) activity was evaluated by l-[ 3 H]-arginine to l-[ 3 H]-citrulline conversion, and cGMP was determined by radioimmunoassay. Platelet expression of NOS3, phosphoserine-1177-NOS3 and soluble guanylyl cyclase (sGC) were quantified by Western blotting. Circulating monocyte–platelet aggregates (MPA) were measured by flow cytometry. Results: Basal NOS activity was similar in both groups. By contrast, whereas both albuterol and collagen stimulated platelet NOS in younger subjects, stimulation was absent in older subjects. Platelet NOS3 expression was similar in both age groups, but NOS3 serine-1177 phosphorylation was greater in younger subjects. Basal, albuterol- and collagen-stimulated cGMP, as well as sGC expression, were all greater in younger than older subjects, and within the younger group both cGMP (basal and stimulated) and sGC expression were greater in women than in men. Circulating MPA were greater in older subjects and, whilst NOS inhibition increased MPA further in both groups, it did so to a lesser extent in the older age bracket. Conclusions: These data suggest that platelet NO production and responsiveness decrease with age, and this is reflected in increased circulating MPA.