Comparison of hypotension incidence between remimazolam and propofol in patients with hypertension undergoing neurosurgery: prospective, randomized, single-blind trial.

BACKGROUND: Remimazolam, a newer benzodiazepine that targets the GABAA receptor, is thought to allow more stable blood pressure management during anesthesia induction. In contrast, propofol is associated with vasodilatory effects and an increased risk of hypotension, particularly in patients with comorbidities. This study aimed to identify medications that can maintain stable vital signs throughout the induction phase. METHODS: We conducted a single-center, two-group, randomized controlled trial to investigate and compare the incidence of hypotension between remimazolam- and propofol-based total intravenous anesthesia (TIVA). We selected patients aged between 19 and 75 years scheduled for neurosurgery under general anesthesia, who were classified as American Society of Anesthesiologists Physical Status I-III and had a history of hypertension. RESULTS: We included 94 patients in the final analysis. The incidence of hypotension was higher in the propofol group (91.3%) than in the remimazolam group (85.4%; P = 0.057). There was no significant difference in the incidence of hypotension among the various antihypertensive medications despite the majority of patients being on multiple medications. In comparison with the propofol group, the remimazolam group demonstrated a higher heart rate immediately after intubation. CONCLUSIONS: Our study indicated that the hypotension incidence of remimazolam-based TIVA was comparable to that of propofol-based TIVA throughout the induction phase of EEG-guided anesthesia. Both remimazolam and propofol may be equally suitable for general anesthesia in patients undergoing neurosurgery. TRIAL REGISTRATION: Clinicaltrials.gov (NCT05164146).

Medical management for cerebellar mutism syndrome following posterior fossa surgery: A systematic review.

INTRODUCTION: Cerebellar mutism syndrome (CMS) is a serious complication of posterior fossa surgeries affecting mainly pediatric age group. The pathophysiology is still not fully understood. It adversely affects the recovery of patients. There is no definitive and standardized management for CMS. However pharmacological therapy has been used in reported cases with variable effectiveness. We aim through this review to summarize the available evidence on pharmacological agents used to treat CMS. METHOD: A thorough systematic review until December 2022, was conducted using PubMed Central, Embase, and Web of Science, databases to identify case reports and case series of CMS patients who underwent posterior fossa surgery and received pharmacological treatment. Patients with pathologies other than posterior fossa lesions were excluded from the study. RESULTS: Of 592 initial studies, 8 studies met our eligibility criteria for inclusion, with 3 more studies were added through manual search; reporting on 13 patients. The median age of 13 years (Standard deviation SD=10.60). The most frequent agent used was Bromocriptine. Other agents were fluoxetine, midazolam, zolpidem, and arpiprazole. Most patients recovered within 48 hours of initiating medical therapy. The median follow-up period was 4 months (SD=13.8). All patients showed complete recovery at the end of follow-up period. CONCLUSION: Cerebellar mutism syndrome is reported after posterior fossa surgeries, despite attempts to identify risk factors, pathophysiology, and management of CMS, it remains a challenging condition with significant morbidity. Different Pharmacological treatments have been proposed with promising results. Further studies and formalized clinical trials are needed to evaluate available options and their effectiveness.

Intermittend pneumatic venous thrombembolism (VTE) prophylaxis during neurosurgical procedures.

BACKGROUND: The management of perioperative venous thrombembolism (VTE) prophylaxis is highly variable between neurosurgical departments and general guidelines are missing. The main issue in debate are the dose and initiation time of pharmacologic VTE prevention to balance the risk of VTE-based morbidity and potentially life-threatening bleeding. Mechanical VTE prophylaxis with intermittend pneumatic compression (IPC), however, is established in only a few neurosurgical hospitals, and its efficacy has not yet been demonstrated. The objective of the present study was to analyze the risk of VTE before and after the implementation of IPC devices during elective neurosurgical procedures. METHODS: All elective surgeries performed at our neurosurgical department between 01/2018-08/2022 were investigated regarding the occurrence of VTE. The VTE risk and associated mortality were compared between groups: (1) only chemoprophylaxis (CHEMO; surgeries 01/2018-04/2020) and (2) IPC and chemoprophylaxis (IPC; surgeries 04/2020-08/2022). Furthermore, general patient and disease characteristics as well as duration of hospitalization were evaluated and compared to the VTE risk. RESULTS: VTE occurred after 38 elective procedures among > 12.000 surgeries. The number of VTEs significantly differed between groups with an incidence of 31/6663 (0.47%) in the CHEMO group and 7/6688 (0.1%) events in the IPC group. In both groups, patients with malignant brain tumors represented the largest proportion of patients, while VTEs in benign tumors occurred only in the CHEMO group. CONCLUSION: The use of combined mechanical and pharmacologic VTE prophylaxis can significantly reduce the risk of postoperative thromboembolism after neurosurgical procedures and, therefore, reduce mortality and morbidity.

Direct resection is a safe and effective strategy to control seizures in patients with hypothalamic hamartoma.

Achieving favorable seizure outcomes is challenging in patients with seizures resulting from hypothalamic hamartoma. Although minimally invasive and non-invasive surgical procedures are used to treat this population, these procedures have limitations. Therefore, we analyzed the outcomes of patients with hypothalamic hamartoma following direct resection. We included 159 patients with hypothalamic hamartoma who underwent direct resection using the transcallosal interforniceal approach between 2011 and 2018. The relationships between clinical parameters and seizure outcomes were analyzed. In total, 55.3% achieved gross total resection and 25.2% underwent near-total resection. Of all patients, 79.2% were overall seizure-free at one year, but this number dropped to 77.0% at more than five years. Moreover, 88.4% (129/146) reached gelastic seizure (GS)-free status at one year and this number increased to 89.0% (97/109) at more than five years. Seventy-one patients took antiseizure medication (ASM) long-term, 68 took it for one year, and 11 took it for one-half year. The duration of ASM consumption (p < 0.001) and extent of hypothalamic hamartoma resection (p = 0.016) were significant independent predictors of long-term overall seizure-free survival, while the duration of ASM consumption (p = 0.011) and extent of hypothalamic hamartoma resection (p = 0.026) were significant independent predictors of long-term GS-free survival. Most patients' behavior, school performance, and intelligence were not affected after surgery. Direct resection is effective and safe strategy for patients with hypothalamic hamartomas. Hypothalamic hamartomas should be removed as completely as possible, and patients should take ASM long-term following surgery to reach long-term overall seizure-free or GS-free status.

New-onset psychogenic nonepileptic seizures after intracranial neurosurgery: A meta-analysis.

BACKGROUND: The epidemiology of psychogenic non-epileptic seizures (PNES) is still unclear. Although approximately 14 million people need neurosurgical care annually, there is a dearth of thorough analysis on PNES occurrence following surgery. This study seeks to estimate the proportion of newly diagnosed PNES. METHODS: We conducted a literature search of the PubMed, Ovid, CINAHL, and Cochrane Library databases up to December 2023. We identified studies using an observational design on the occurrence of PNES in patients who underwent intracranial surgery, and confirmed diagnosis using video-EEG. Estimates are reported as proportions using random effects models. We reported both 95 % CIs and prediction intervals (PI). We assessed the risk of bias and identified the pooled odds ratio (OR) for mutually exclusive groups. The heterogeneity was investigated using the I² statistic and significance determined using Cochran's Q-test. Post-hoc Egger's regression test, and several sensitivity analyses were performed. This study was registered in PROSPERO (CRD42023488611). RESULTS: Of the 1766 unique studies identified, 86 were selected for full-text review. Eight studies (n = 3,699) were eligible for inclusion. Studies, spanning from 1995 to 2017, primarily focused on epilepsy surgeries. The pooled proportion was 3 % (95 % CI 2 %-5 %; 95 % PI 0 %-11 %). Temporal resections indicated twofold increase of PNES comparing to either resections (OR 2.05, 95 %CI 0.81-5.19). The risk of bias assessment indicated satisfactory quality for included studies, and heterogeneity in estimates was mainly explained by publication year of studies and their rounded sample size. CONCLUSIONS: Given the estimations, there is expected impact of intracranial procedures on functional seizures epidemiology. Further efforts need to understand the contribution of brain resections to PNES incidence.

Postoperative Neurologic Outcome in Patients Undergoing Resective Surgery for Parietal Lobe Epilepsy: A Systematic Review.

BACKGROUND AND OBJECTIVES: Parietal lobe epilepsy (PLE) surgery can be an effective treatment for selected patients with intractable epilepsy but can be associated with the risk of serious neurologic deficits. We performed a systematic review of the literature to obtain a comprehensive summary of the frequency and types of new postoperative neurologic deficits in patients undergoing PLE resective surgery. METHODS: We searched MEDLINE, Embase, and Cochrane Central Register of Controlled Trials for articles published between January 1, 1990, and April 28, 2022. We included studies that reported postoperative neurologic outcome following PLE resective surgery confined to the parietal lobe. We required that studies included ≥5 patients. The data collected included demographic information and specific details of postoperative neurologic deficits. When available, individual patient data were collected. We used the Risk of Bias in Nonrandomized Studies of Interventions tool to assess the risk of bias and Grading of Recommendations Assessment, Development, and Evaluation to assess the quality of the evidence. RESULTS: Of the 3,461 articles screened, 33 studies met the inclusion criteria. A total of 370 patients were included. One hundred patients (27.0%) had a new deficit noted postoperatively. Approximately half of the patients with deficits experienced only transient deficits. Motor deficits were the most commonly identified deficit. The rates of motor deficits noted after PLE surgery were 5.7%, 3.2%, and 2.2% for transient, long-term, and duration not specified, respectively. Sensory and visual field deficits were also commonly reported. Gerstmann syndrome was noted postoperatively in 4.9% of patients and was almost always transient. Individual patient data added information on parietal lobe subregion postoperative neurologic outcome. DISCUSSION: Our systematic review provides a comprehensive summary of the frequency and types of neurologic deficits associated with PLE surgery. A significant percentage of postoperative deficits are transient. In addition to the expected sensory and visual deficits, PLE surgery is associated with a notable risk of motor deficits. The available literature has important deficiencies. Our study highlights gaps in the literature and provides recommendations for future directions. TRIAL REGISTRATION INFORMATION: This systematic review was registered on PROSPERO (CRD42022313108, May 26, 2022).

Predictors of early and late postoperative seizures in meningioma patients: a systematic review and meta-analysis.

Meningioma is the most common type of primary brain tumor which presents with a variety of neurological manifestations. Surgical resection tends to be the preferred treatment. The occurrence of seizures after resection is common, which occur either early, within seven days of operation, or late. Our meta-analysis investigated the possible predictors of early and late postoperative seizures. We assessed the relevant observational studies on predictors of postoperative seizures published in PubMed, Scopus, and Web of Science from January 2000 to September 2022, and those that met inclusion criteria were included. We calculated the association between potential predicting factors and postoperative seizures, odds ratios (ORs) with 95% confidence intervals (CIs) applying either random or fixed-effect models. The early and late postoperative seizures were evaluated individually. Thirteen observational studies involving 4176 patients were included. Seizures occurred in 250 (6%) and 584 (14%) patients, respectively, in the early and late postoperative phases. Shared predictors for early and late seizures included tumors involving the motor cortex (OR = 2.7; 95% CI: 1.67-4.38, OR = 2.46; 95% CI: 1.68-3.61), postoperative neurological deficit (OR = 4.68; 95% CI: 2.67-8.22, OR = 2.01; 95% CI: 1.39-2.92), and preoperative seizures (OR = 2.52; 95% CI: 1.82-3.49, OR = 4.35; 95% CI: 3.29-5.75). Peritumoral edema (OR = 1.99; 95% CI: 1.49-2.64) was a significant factor only among late postoperative seizure patients while surgical complications (OR = 3.77; 95% CI: 2.39-5.93) was a significant factor solely for early postoperative seizures. Meningioma patients commonly experience early and late postoperative seizures. Identifying predictors of postoperative seizures is essential to diagnose and manage them effectively.

Hemopatch® as a primary dural sealant in cranial neurosurgery: Technical note and a retrospective study.

OBJECTIVES: To determine the effectiveness and safety of Hemopatch® as a primary dural sealant in preventing CSF leakage following cranial surgery. Cerebrospinal fluid (CSF) leaks occur in cranial operations and are associated with significant patient burden and expense. The use of Hemopatch® as a dural sealant in cranial neurosurgical procedures is described and analyzed in this study. METHODS: Data were retrospectively collected from all patients who underwent a craniotomy for various neurosurgical indications where Hemopatch® was used as the primary dural sealant between June 2017 and June 2022. Infection and CSF leak were the main indicators evaluated after surgery. RESULTS: A total of 119 consecutive patients met our inclusion criteria. The median was age 41.5 years, and 52.5% were female. The mean follow-up period was 2.3 years (7 months to 6 years). There were 110 (92.44%) supratentorial and 9 (7.56%) infratentorial craniotomies. Postoperative CSF leak was reported in 2 patients (1.68%), one in each cohort. Postoperative infection occurred in one patient (0.84%). CONCLUSION: The results suggest that using Hemopatch® as a dural sealant in cranial surgery is effective and safe. After supra-/infratentorial craniotomies, the rate of postoperative adverse events in our sample was within the range of known surgical revision rates. Future randomized clinical studies are required to confirm our encouraging findings.

Risk factors for cerebral edema following aneurysm clipping in patients with aneurysmal subarachnoid hemorrhage.

OBJECTIVES: To investigate the factors that contribute to the development of cerebral edema after aneurysm clipping in individuals with aneurysmal subarachnoid hemorrhage (aSAH). METHODS: A total of 232 patients with aSAH caused by rupture and treated with aneurysm clipping were included in the retrospective analysis of clinical data. Postoperatively, the participants were categorized into two groups based on the presence or absence of cerebral edema: a complication group (n=33) and a non-complication group (n=199).A comparison was made between the overall data of the 2 groups. RESULTS: In the complication group, there were higher proportions of patients experiencing recurrent bleeding, aneurysm in the posterior circulation, Fisher grade III-IV, World Federation of Neurosurgical Societies (WFNS) grade II, Hunt-Hess grade III-IV, concomitant hypertension, duration from onset to operation ≥12 h, and concomitant hematoma compared to the non-complication group (p<0.05). Cerebral edema after aneurysm clipping was associated with several risk factors including repeated bleeding, aneurysm in the back of the brain, Fisher grade III-IV, WFNS grade II, Hunt-Hess grade III-IV, simultaneous high blood pressure and hematoma, and a duration of at least 12 hours from the start of symptoms to the surgical procedure (p<0.05). CONCLUSION: In patients with aSAH, the risk of cerebral edema after aneurysm clipping is increased by recurrent bleeding, aneurysm in the posterior circulation, Fisher grade III-IV, WFNS grade II, Hunt-Hess grade III-IV, concomitant hypertension and hematoma, and duration of ≥12 h from onset to operation.

Perioperative Neurocognitive Function in Glioma Surgery.

PURPOSE OF REVIEW: This review provides a concise overview of the recent literature regarding preoperative and postoperative neurocognitive functioning (NCF) in patients with glioma. Brief discussion also covers contemporary intraoperative brain mapping work, with a focus on potential influence of mapping upon NCF outcomes following awake surgery. RECENT FINDINGS: Most patients with glioma exhibit preoperative NCF impairment, with severity varying by germ line and tumoral genetics, tumor grade, and lesion location, among other characteristics. Literature regarding postoperative NCF changes is mixed, though numerous studies indicate a majority of patients exhibit immediate and short-term worsening. This is often followed by recovery over several months; however, a substantial portion of patients harbor persisting declines. Decline appears related to surgically-induced structural and functional brain alterations, both local and distal to the tumor and resection cavity. Importantly, NCF decline may be mitigated to some extent by intraoperative brain mapping, including mapping of both language-mediated and nonverbal functions. Research regarding perioperative NCF in patients with glioma has flourished over recent years. While this has increased our understanding of contributors to NCF and risk of decline associated with surgical intervention, more work is needed to better preserve NCF throughout the disease course.

Health care-associated infections after surgical treatment of ruptured intracranial aneurysms.

BACKGROUND: Aneurysmal subarachnoid hemorrhage (SAH) is catastrophic, and microsurgery for ruptured intracranial aneurysms is one of the preventive modalities for rebleeding. However, patients remain at high risk of medical morbidities after surgery, one of the most important of which is health care-associated infections (HAIs). We analyzed the incidence and risk factors of HAIs, as well as their association with the outcomes after surgical treatment of ruptured aneurysms. METHODS: We retrospectively enrolled 607 patients with SAH who had undergone surgery for intracranial aneurysms. Information was retrieved from the database using codes of the International Classification of Diseases, Ninth Revision, Clinical Modification. RESULTS: Of the 607 patients, 203 were male and 404 were female. HAIs occurred in 113 patients, accounting for 18.6 % of the population. The independent risk factors for HAIs included age ((p = 0.035), hypertension ((p = 0.042), convulsion ((p = 0.023), external ventricular drain ((p = 0.035), ventricular shunt ((p = 0.033), and blood transfusion ((p = 0.001). The mean length of hospital stay was 25.3 ± 18.2 and 18.8 ± 15.3 days for patients with and without HAIs, respectively ((p = 0.001). The in-hospital mortality rates were 11.5 % in the HAIs group, and 14.0 % in the non-HAIs group ((p = 0.490). CONCLUSION: HAIs are a frequent complication in patients with SAH who underwent surgery for ruptured intracranial aneurysms. The length of hospital stay is remarkably longer for patients with HAIs, and to recognize and reduce the modifiable risks should be implemented to improve the quality of patient care.

Risk Factors of Intraoperative Pressure Injury in Adult Patients Undergoing Neurologic Surgery.

GENERAL PURPOSE: To present research investigating the incidence of and risk factors associated with intraoperative pressure injury in patients undergoing neurologic surgery at Xiangya Hospital, Central South University in China. TARGET AUDIENCE: This continuing education activity is intended for physicians, physician assistants, nurse practitioners, and registered nurses with an interest in skin and wound care. LEARNING OBJECTIVES/OUTCOMES: After participating in this educational activity, the participant will:1. Identify the incidence of intraoperative pressure injuries (PIs) in patients undergoing neurologic surgery at Xiangya Hospital, Central South University in China.2. Describe risk factors for intraoperative PI.3. Outline strategies to help mitigate intraoperative PI risk.

Intraoperative pressure injury (PI) development is an adverse event that impacts thousands of patients globally and is associated with extended hospital stays and increased risk of mortality. To investigate the incidence of intraoperative PI in patients undergoing neurologic surgery and identify associated risk factors. A total of 1,728 patients who underwent neurosurgery in Xiangya Hospital, Central South University between January 2021 and December 2022 were included in this retrospective study. The authors collected patients' demographic data and clinical characteristics and used univariate and multivariate regression to evaluate significant PI risk factors. Intraoperative PI was observed in 1.8% of all surgical cases (n = 31). Having a body mass index greater than 24 kg/m2 (odds ratio, 3.87; 95% CI, 1.62­9.23; P = .002), being in a lateral position (odds ratio, 2.53; 95% CI, 1.04­6.17; P = .042) or a prone position (odds ratio, 10.43; 95% CI, 3.37­32.23; P < .001), and having a longer operation time (cutoff point at 7.92 hours for increased risk of PI; odds ratio, 1.36; 95% CI, 1.21­1.53; P < .001) were significant risk factors for intraoperative PI. This study identified three independent risk factors for intraoperative PI development: body position, surgery duration, and high body mass index. These findings can help OR nurses identify patients who are vulnerable to intraoperative PI and provide appropriate preventive measures. For these patients, perioperative protection and frequent microrepositioning during surgery would be indispensable.

Diagnostic, monitoring, and prognostic value of combined detection of cerebrospinal fluid heparin-binding protein, interleukin-6, interleukin-10, and procalcitonin for post-neurosurgical intracranial infection.

OBJECTIVE: Intracranial infection is a common complication after neurosurgery and can increase the length of hospital stay, affect patient prognosis, and increase mortality. We aimed to investigate the value of the combined detection of cerebrospinal fluid (CSF) heparin-binding protein (HBP), interleukin-6 (IL-6), interleukin-10 (IL-10), and procalcitonin (PCT) for post-neurosurgical intracranial infection. METHODS: This study assessed the diagnostic values of CSF HBP, IL-6, IL-10, PCT levels, and combined assays for post-neurosurgical intracranial infection with the area under the receiver operating characteristic (ROC) curve by retrospectively analysing biomarkers of post-neurosurgical patients. RESULTS: The CSF HBP, IL-6, IL-10, and PCT levels were significantly higher in the infected group than the uninfected group and the control group (P < 0.001). The indicators in the groups with severe intracranial infections were significantly higher than those in the groups with mild intracranial infections (P < 0.001), and the groups with poor prognoses had significantly higher indexes than the groups with good prognoses. According to the ROC curve display, the AUC values of CSF HBP, IL-6, IL-10, and PCT were 0.977 (95 % CI 0.952-1.000), 0.973 (95 % CI 0.949-0.998), 0.884 (95 % CI 0.823-0.946), and 0.819 (95 % CI 0.733-0.904), respectively. The AUC of the combined test was 0.996 (95 % CI 0.989-1.000), which was higher than those of the four indicators alone. CONCLUSION: The combined detection can be an important indicator for the diagnosis and disease monitoring of post-neurosurgical intracranial infection.

Postoperative Airway Management after Anterior Cervical Spine Surgery: Retrospective Neurosurgical Multicenter Study.

Airway complications that occur after anterior cervical spine surgery pose a life-threatening risk, which encompasses complications including prolonged intubation, unplanned reintubation, and/or necessity of tracheostomy. The present study aimed to identify the surgical risks associated with postoperative airway complications in neurosurgical training institutes. A retrospective, multicenter, observational review of data from 365 patients, who underwent anterior cervical spine surgery between 2018 and 2022, at three such institutes was carried out. Postoperative airway complication was defined as either the need for prolonged intubation on the day of surgery or the need for unplanned reintubation. The perioperative medical information was obtained from their medical records. The average age of the cohort was over 60 years, with males comprising approximately 70%. Almost all surgeries predominantly involved anterior cervical discectomy and fusion or anterior cervical corpectomy and fusion, with most surgeries occurring at the level of C5/6. In total, 363 of 365 patients (99.5%) were extubated immediately after surgery, and the remaining two patients were kept under intubation because of the risk of airway complications. Of the 363 patients who underwent extubation immediately after surgery, two (0.55%) required reintubation because of postoperative airway complications. Patients who experienced airway complications were notably older and exhibited a significantly lower body mass index. The results of this study suggested that older and frailer individuals are at an elevated risk for postoperative airway complications, with immediate postoperative extubation generally being safe but requiring careful judgment in specific cases.

Complications and visual outcomes following surgical resection of pediatric optic pathway/hypothalamic gliomas: a systematic review and meta-analysis.

Pediatric optic pathway/hypothalamic gliomas (OPHG) pose challenges in treatment due to their location and proximity to vital structures. Surgical resection plays a key role in the management of OPHG especially when the tumor exhibits mass effect and causes symptoms. However, data regarding outcomes and complications of surgical resection for OPHG remains heterogenous. The authors performed a systematic review on pediatric OPHG in four databases: PubMed, EMBASE, Cochrane Library, and Google Scholar. We included studies that reported on the visual outcomes and complications of OPHG resection. A meta-analysis was performed and reported per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. A total of 26 retrospective studies were included. Seven hundred ninety-seven pediatric patients with OPHG undergoing surgical resection were examined. A diagnosis of NF1 was confirmed in 9.7%. Gross total resection was achieved in 36.7%. Intraorbital optic pathway gliomas showed a significantly higher gross total resection rate compared to those located in the chiasmatic/hypothalamic region (75.8% vs. 9.6%). Postoperatively, visual acuity improved in 24.6%, remained unchanged in 68.2%, and worsened in 18.2%. Complications included hydrocephalus (35.4%), anterior pituitary dysfunction (19.6%), and transient diabetes insipidus (29%). Tumor progression post-resection occurred in 12.8%, through a mean follow-up of 53.5 months. Surgical resection remains an essential strategy for treating symptomatic and large pediatric OPHG and can result in favorable vision outcomes in most patients. Careful patient selection is critical. Patients should be monitored for hydrocephalus development postoperatively and followed up to assess for tumor progression and adjuvant treatment necessity.

Results from a first-in-human phase I safety trial to evaluate the use of a vascularized pericranial/temporoparietal fascial flap to line the resection cavity following resection of newly diagnosed glioblastoma.

PURPOSE: The efficacy of systemic therapies for glioblastoma (GBM) remains limited due to the constraints of systemic toxicity and blood-brain barrier (BBB) permeability. Temporoparietal fascial flaps (TPFFs) and vascularized peri cranial flaps (PCF) are not restricted by the blood-brain barrier (BBB), as they derive their vascular supply from branches of the external carotid artery. Transposition of a vascularized TPFF or PCF along a GBM resection cavity may bring autologous tissue not restricted by the BBB in close vicinity to the tumor bed microenvironment, permit ingrowth of vascular channels fed by the external circulation, and offer a mechanism of bypassing the BBB. In addition, circulating immune cells in the vascularized flap may have better access to tumor-associated antigens (TAA) within the tumor microenvironment. We conducted a first-in-human Phase I trial assessing the safety of lining the resection cavity with autologous TPFF/PCF of newly diagnosed patients with GBM. METHODS: 12 patients underwent safe, maximal surgical resection of newly diagnosed GBMs, followed by lining of the resection cavity with a pedicled, autologous TPFF or PCF. Safety was assessed by monitoring adverse events. Secondary analysis of efficacy was examined as the proportion of patients experiencing progression-free disease (PFS) as indicated by response assessment in neuro-oncology (RANO) criteria and overall survival (OS). The study was powered to determine whether a Phase II study was warranted based on these early results. For this analysis, subjects who were alive and had not progressed as of the date of the last follow-up were considered censored and all living patients who were alive as of the date of last follow-up were considered censored for overall survival. For simplicity, we assumed that a 70% PFS rate at 6 months would be considered an encouraging response and would make an argument for further investigation of the procedure. RESULTS: Median age of included patients was 57 years (range 46-69 years). All patients were Isocitrate dehydrogenase (IDH) wildtype. Average tumor volume was 56.6 cm3 (range 14-145 cm3). Resection was qualified as gross total resection (GTR) of all of the enhancing diseases in all patients. Grade III or above adverse events were encountered in 3 patients. No Grade IV or V serious adverse events occurred in the immediate post-operative period including seizure, infection, stroke, or tumor growing along the flap. Disease progression at the site of the original tumor was identified in only 4 (33%) patients (median 23 months, range 8-25 months), 3 of whom underwent re-operation. Histopathological analyses of those implanted flaps and tumor bed biopsy at repeat surgery demonstrated robust immune infiltrates within the transplanted flap. Importantly, no patient demonstrated evidence of tumor infiltration into the implanted flap. At the time of this manuscript preparation, only 4/12 (33%) of patients have died. Based on the statistical considerations above and including all 12 patients 10/12 (83.3%) had 6-month PFS. The median PFS was 9.10 months, and the OS was 17.6 months. 4/12 (33%) of patients have been alive for more than two years and our longest surviving patient currently is alive at 60 months. CONCLUSIONS: This pilot study suggests that insertion of pedicled autologous TPFF/PCF along a GBM resection cavity is safe and feasible. Based on the encouraging response rate in 6-month PFS and OS, larger phase II studies are warranted to assess and reproduce safety, feasibility, and efficacy. TRIAL REGISTRATION NUMBER AND DATE OF REGISTRATION FOR PROSPECTIVELY REGISTERED TRIALS: ClinicalTrials.gov ID NCT03630289, dated: 08/02/2018.