Dose optimization of second window indocyanine green in meningioma patients.

OBJECTIVE: Surgery remains the first line treatment for meningiomas and can benefit from fluorescence-guided surgical techniques such as second-window indocyanine green (SWIG). In the current study, we compared the use of the standard SWIG dose of 5.0 mg/kg relative to 2.5 mg/kg indocyanine green (ICG) in meningioma patients. METHODS: Patients were prospectively enrolled in an IRB-approved study of SWIG and received either the standard dose of 5.0 mg/kg or a reduced dose of 2.5 mg/kg of ICG around 24 h prior to their surgery. Intraoperative near-infrared fluorescence imaging was performed with exo- and endoscopic systems. Signal-to-background ratio (SBR) was calculated to quantify fluorescence and was compared between 5.0 mg/kg and 2.5 mg/kg ICG. All patients received pre-operative MRI and, in select cases, the pre-operative MRI was correlated to intraoperative fluorescence imaging. RESULTS/DISCUSSION: In the current study, we found no significant difference in the SBR of meningiomas in patients that were administered with either 5.0 mg/kg or 2.5 mg/kg ICG. However, in five patients that received the standard-dose SWIG regimen of 5.0 mg/kg ICG we observed dose-related fluorescence quenching - referred to as "inversion" - that interfered with tumor visualization during fluorescence-guided surgery (FGS). When correlated to pre-operative MRI, a similar rim pattern was observed around the primary tumor on T2 FLAIR, which, in retrospect, could be used as a predictor for inversion during FGS in meningioma patients receiving standard-dose ICG. CONCLUSION: This study demonstrated that a reduced ICG dose was as effective as standard-dose SWIG in meningioma patients. We therefore recommend to adjust the standard ICG dose for meningioma patients to 2.5 mg/kg particularly when rim enhancement is observed on pre-operative T2 FLAIR.

A multi-institutional machine learning algorithm for prognosticating facial nerve injury following microsurgical resection of vestibular schwannoma.

Vestibular schwannomas (VS) are the most common tumor of the skull base with available treatment options that carry a risk of iatrogenic injury to the facial nerve, which can significantly impact patients' quality of life. As facial nerve outcomes remain challenging to prognosticate, we endeavored to utilize machine learning to decipher predictive factors relevant to facial nerve outcomes following microsurgical resection of VS. A database of patient-, tumor- and surgery-specific features was constructed via retrospective chart review of 242 consecutive patients who underwent microsurgical resection of VS over a 7-year study period. This database was then used to train non-linear supervised machine learning classifiers to predict facial nerve preservation, defined as House-Brackmann (HB) I vs. facial nerve injury, defined as HB II-VI, as determined at 6-month outpatient follow-up. A random forest algorithm demonstrated 90.5% accuracy, 90% sensitivity and 90% specificity in facial nerve injury prognostication. A random variable (rv) was generated by randomly sampling a Gaussian distribution and used as a benchmark to compare the predictiveness of other features. This analysis revealed age, body mass index (BMI), case length and the tumor dimension representing tumor growth towards the brainstem as prognosticators of facial nerve injury. When validated via prospective assessment of facial nerve injury risk, this model demonstrated 84% accuracy. Here, we describe the development of a machine learning algorithm to predict the likelihood of facial nerve injury following microsurgical resection of VS. In addition to serving as a clinically applicable tool, this highlights the potential of machine learning to reveal non-linear relationships between variables which may have clinical value in prognostication of outcomes for high-risk surgical procedures.

Pain Outcomes Following Endoscopic Microvascular Decompression for Trigeminal Neuralgia Based on Vascular Compression Type.

Background Arterial compression of the trigeminal nerve at the root entry zone has been the long-attributed cause of compressive trigeminal neuralgia despite numerous studies reporting distal and/or venous compression. The impact of compression type on patient outcomes has not been fully elucidated. Objective We categorized vascular compression (VC) based on vessel and location of compression to correlate pain outcomes based on compression type. Methods A retrospective video review of 217 patients undergoing endoscopic microvascular decompression for trigeminal neuralgia categorizing VC into five distinct types, proximal arterial compression (VC1), proximal venous compression (VC2), distal arterial compression (VC3), distal venous compression (VC4), and no VC (VC5). VC type was correlated with postoperative pain outcomes at 1 month ( n = 179) and last follow-up (mean = 42.9 mo, n = 134). Results At 1 month and longest follow-up, respectively, pain was rated as "much improved" or "very much improved" in 89 69% of patients with VC1, 86.6 and 62.5% of patients with VC2, 100 and 87.5% of patients with VC3, 83 and 62.5% of patients with VC4, and 100 and 100% of patients with VC5. Multivariate analysis demonstrated VC4 as a significant negative of predictor pain outcomes at 1 month, but not longest follow-up, and advanced age as a significant positive predictor. Conclusion The degree of clinical improvement in all types of VC was excellent, but at longest follow-up VC type was not a significant predictor out outcome. However distal venous compression was significantly associated with worse outcomes at 1 month.

A Prospective Phase I/II Clinical Trial of High-Dose Proton Therapy for Chordomas and Chondrosarcomas.

Purpose: The purpose of this study was to evaluate the feasibility and safety of dose-escalated proton beam therapy for treating chordomas and chondrosarcomas of the skull base and spine. Methods: A prospective cohort of 54 patients (42 with chordomas and 12 with chondrosarcomas) was enrolled between 2010 and 2018. The primary endpoints were feasibility and <20% rate of acute grade ≥3 toxicity, and secondary endpoints included cancer-specific outcomes and toxicities. Patients were followed with magnetic resonance imaging or computed tomography at 3-month intervals. Proton beam therapy was delivered with doses up to 79.2 Gy using protons only, combination protons/intensity modulated radiation therapy (IMRT), or IMRT only. Results: Feasibility endpoints were met, with only 2 out of 54 patient radiation therapy plans failing to meet dosimetric constraints with protons, and 4 out of 54 experiencing a delay or treatment break >5 days, none for toxicities related to treatment. There were no grade 4 acute toxicities and 1 grade 3 acute toxicity (sensory neuropathy). The only 2 grade 3 late toxicities recorded, osteoradionecrosis and intranasal carotid blowout (mild and not emergently treated), occurred in a single patient. We report overall survival as 83% at 5 years, with local failure-free survival and progression-free survival rates of 72% and 68%, respectively. Five patients developed distant disease, and among the 9/54 patients who died, 4 deaths were not attributed to treatment or recurrence. Conclusions: Our findings suggest that high-dose proton therapy alone or in combination with IMRT is a safe and effective treatment option for chordomas and chondrosarcomas of the skull base and spine.

Intraoperative visualization of cranial nerve schwannomas using second-window indocyanine green: A case series.

BACKGROUND: Second Window Indocyanine Green (SWIG) is a novel intraoperative imaging technique that uses near-infrared (NIR) light for intra-operative tumor visualization using the well-known fluorophore indocyanine green (ICG). Because schwannomas often incorporate the nerve into the encapsulated tumor and impinge on surrounding neural structures, SWIG is a promising technique to improve tumor resection while sparing the nerve. OBJECTIVE: To demonstrate the use of SWIG in resection of cranial nerve schwannomas. METHODS: Three patients with cranial nerve schwannomas (i.e., trigeminal, vestibular, and vagus) underwent SWIG-guided resection. During surgery, NIR visualization was used intermittently used to detect fluorescence to guide resection. Signal-to-background ratio was then calculated to quantify fluorescence. RESULTS: Patients were infused with ICG at a dose of 5.0 mg/kg 24 hours before surgery. Each patient achieved total or near-total resection and relief of symptoms with lack of recurrence at six-month follow-up. The average SBR calculated was 3.79, comparable to values for SWIG-guided resection of other brain and spine tumors. CONCLUSION: This case series is the first published report of trigeminal and vagus nerve schwannoma resection using the SWIG technique and suggests that SWIG may be used to detect all schwannomas, alongside many other types of brain tumor. This paper also demonstrates the importance of preoperative ICG infusion timing and discusses the inverse pattern of NIR signal that may be observed when infusion occurs outside of the optimal timing. This provides direction for future studies investigating the administration of SWIG to resect cranial nerve schwannomas and other brain tumors.

The relevance of biologically effective dose for pain relief and sensory dysfunction after Gamma Knife radiosurgery for trigeminal neuralgia: an 871-patient multicenter study.

OBJECTIVE: Recent studies have suggested that biologically effective dose (BED) is an important correlate of pain relief and sensory dysfunction after Gamma Knife radiosurgery (GKRS) for trigeminal neuralgia (TN). The goal of this study was to determine if BED is superior to prescription dose in predicting outcomes in TN patients undergoing GKRS as a first procedure. METHODS: This was a retrospective study of 871 patients with type 1 TN from 13 GKRS centers. Patient demographics, pain characteristics, treatment parameters, and outcomes were reviewed. BED was compared with prescription dose and other dosimetric factors for their predictive value. RESULTS: The median age of the patients was 68 years, and 60% were female. Nearly 70% of patients experienced pain in the V2 and/or V3 dermatomes, predominantly on the right side (60%). Most patients had modified BNI Pain Intensity Scale grade IV or V pain (89.2%) and were taking 1 or 2 pain medications (74.1%). The median prescription dose was 80 Gy (range 62.5-95 Gy). The proximal trigeminal nerve was targeted in 77.9% of cases, and the median follow-up was 21 months (range 6-156 months). Initial pain relief (modified BNI Pain Intensity Scale grades I-IIIa) was noted in 81.8% of evaluable patients at a median of 30 days. Of 709 patients who achieved initial pain relief, 42.3% experienced at least one pain recurrence after GKRS at a median of 44 months, with 49.0% of these patients undergoing a second procedure. New-onset facial numbness occurred in 25.3% of patients after a median of 8 months. Age ≥ 63 years was associated with a higher probability of both initial pain relief and maintaining pain relief. A distal target location was associated with a higher probability of initial and long-term pain relief, but also a higher incidence of sensory dysfunction. BED ≥ 2100 Gy2.47 was predictive of pain relief at 30 days and 1 year for the distal target, whereas physical dose ≥ 85 Gy was significant for the proximal target, but the restricted range of BED values in this subgroup could be a confounding factor. A maximum brainstem point dose ≥ 29.5 Gy was associated with a higher probability of bothersome facial numbness. CONCLUSIONS: BED and physical dose were both predictive of pain relief and could be used as treatment planning goals for distal and proximal targets, respectively, while considering maximum brainstem point dose < 29.5 Gy as a potential constraint for bothersome numbness.

Multi-institutional Analysis of Endoscopic Sellar Surgical Volumes During the COVID-19 Pandemic.

OBJECTIVE: We sought to quantify trends in operative volumes and complications of endoscopic sellar surgery before and after the COVID-19 pandemic onset. STUDY DESIGN: We performed a retrospective analysis. SETTING: TriNetX database analysis. METHODS: All adults undergoing neuroendoscopy for resection of pituitary tumor (Current Procedural Terminology code 62165) with diagnosis of benign/malignant neoplasm of pituitary gland (D35.2/C75.1) or benign/malignant neoplasm of craniopharyngeal duct (D35.3/C75.2) were included using the TriNetX database for 2 years before (pre-COVID group) and 2 years after (post-COVID group) February 17, 2020. RESULTS: A total of 1238 patients in the pre-COVID group and 1186 patients in the post-COVID group were compared. Age, gender, and race were statistically similar between the groups (P > .05). Surgical volume decreased by 6% in the post-COVID group. In 2020 Q2, operative volume decreased by 19%, and in 2021 Q4 (peak COVID-19 caseload in the United States), operative volumes decreased by 29% compared to 2 years prior. Postoperative complications including meningitis (P = .49), cerebrospinal fluid leak (P = .36), visual field deficits (P = .07), postoperative pneumonia or respiratory failure (P = .42), and 30-day readmission rates (P = .89) were similar between the 2 groups. CONCLUSION: Overall, endoscopic sellar surgery may continue to fluctuate with increased COVID-19 outbreaks. Patient outcomes do not appear to be worsened by decreased operative volumes or delays in nonurgent surgeries.

Candidate Genetic and Molecular Drivers of Dysregulated Adaptive Immune Responses After Traumatic Brain Injury.

Abstract Neuroinflammation is a significant and modifiable cause of secondary injury after traumatic brain injury (TBI), driven by both central and peripheral immune responses. A substantial proportion of outcome after TBI is genetically mediated, with an estimated heritability effect of around 26%, but because of the comparatively small datasets currently available, the individual drivers of this genetic effect have not been well delineated. A hypothesis-driven approach to analyzing genome-wide association study (GWAS) datasets reduces the burden of multiplicity testing and allows variants with a high prior biological probability of effect to be identified where sample size is insufficient to withstand data-driven approaches. Adaptive immune responses show substantial genetically mediated heterogeneity and are well established as a genetic source of risk for numerous disease states; importantly, HLA class II has been specifically identified as a locus of interest in the largest TBI GWAS study to date, highlighting the importance of genetic variance in adaptive immune responses after TBI. In this review article we identify and discuss adaptive immune system genes that are known to confer strong risk effects for human disease, with the dual intentions of drawing attention to this area of immunobiology, which, despite its importance to the field, remains under-investigated in TBI and presenting high-yield testable hypotheses for application to TBI GWAS datasets.

Impact of Frailty on Postoperative Outcomes in Extended Endonasal Skull Base Surgery for Suprasellar Pathologies.

OBJECTIVE: Frailty metrics estimate a patient's ability to tolerate physiologic stress and there are limited frailty data in patients undergoing expanded endonasal approaches (EEA) for suprasellar pathologies. Elevated frailty metrics have been associated with increased perioperative complications in patients undergoing craniotomies. We sought to examine this potential relationship in EEA. STUDY DESIGN: Retrospective cohort study. SETTING: Two tertiary academic skull base centers. METHODS: Cases of patients undergoing EEA for suprasellar pathologies were reviewed. Demographic, treatment, survival, and postoperative outcomes data were recorded. Frailty was calculated using validated indexes, including the American Society of Anesthesiologists (ASA) classification, the modified 5-item frailty index (mFI-5), and the Charlson comorbidity index (CCI). Primary outcomes included 30-day medical and surgical complications. RESULTS: A total of 88 patients were included, with 59 (67%) female patients and a mean age of 54 ± 15 years. The most common pathologies included 53 meningiomas (60.2%) and 21 craniopharyngiomas (23.9%). Most patients were ASA class 3 (54.5%) with mean mFI-5 0.82 ± 1.01 and CCI 4.18 ± 2.42. There was no association between increased frailty and 30-day medical or surgical outcomes (including postoperative cerebrospinal fluid leak), prolonged length of hospital stay, or mortality (all P > .05). Higher mFI-5 was associated with an increased risk for 30-day readmission (odds ratio: 2.35, 95% confidence Interval: 1.10-5.64, P = .04). CONCLUSION: Despite the patient population being notably frail, we only identified an increased risk for 30-day readmission and observed no links with deteriorating surgical, medical, or mortality outcomes. This implies that conventional frailty metrics may not effectively align with EEA outcomes.

A surgical decision aid for occipital neuralgia with literature review and single center case series.

BACKGROUND: Occipital neuralgia (ON) is a debilitating headache disorder. Due to the rarity of this disorder and lack of high-level evidence, a clear framework for choosing the optimal surgical approach for medically refractory ON incorporating shared decision making with patients does not exist. METHODS: A literature review of studies reporting pain outcomes of patients who underwent surgical treatment for ON was performed, as well as a retrospective chart review of patients who underwent surgery for ON within our institution. RESULTS: Thirty-two articles met the inclusion criteria. A majority of the articles were retrospective case series (22/32). The mean number of patients across the studies was 34 (standard deviation (SD) 39). Among the 13 studies that reported change in pain score on 10-point scales, a study of 20 patients who had undergone C2 and/or C3 ganglionectomies reported the greatest reduction in pain intensity after surgery. The studies evaluating percutaneous ablative methods including radiofrequency ablation and cryoablation showed the smallest reduction in pain scores overall. At our institution from 2014 to 2023, 11 patients received surgical treatment for ON with a mean follow-up of 187 days (SD 426). CONCLUSION: Based on these results, the first decision aid for selecting a surgical approach to medically refractory ON is presented. The algorithm prioritizes nerve sparing followed by non-nerve sparing techniques with the incorporation of patient preference. Shared decision making is critical in the treatment of ON given the lack of clear scientific evidence regarding the superiority of a particular surgical method.

Vein Morphology in Endoscopic Vein Harvesting: 15-Year Outcomes.

OBJECTIVE: Long-term outcomes of vein morphologies in the endoscopic vein harvesting setting are lacking. We analyzed 15-year follow-up for endoscopic versus open vein harvesting and associated vein morphology outcomes in coronary artery bypass grafting at a single center. METHODS: This single-center, prospectively collected, retrospective, observational study evaluated 15-year major adverse cardiovascular events (MACE) of endoscopic versus open vein harvesting and associated vein morphologies. RESULTS: Among 729 patients, no differences were found between endoscopic and open vein harvesting in MACE hazard ratios despite increased risks with native Hawai'ian, Pacific Islander, and Filipino patients. Asian and Filipino patients had more thin-walled veins and Asian and multirace patients had more vasovasoral branches than White patients. Bifid veins were associated with increased risk of cardiac catheterization. Varicose veins were associated with myocardial infarction, congestive heart failure, and death. Thick-walled veins were associated with revascularization and dense adhesions with cardiac catheterization and revascularization. CONCLUSIONS: Fifteen-year adjusted MACE was similar between endoscopic and open vein harvesting in small coronary targets despite increased risks with native Hawai'ian, Pacific Islander, and Filipino patients. Bifid, varicose, thick-walled veins, and dense adhesions had worse MACE.

Fluorescence lifetime of injected indocyanine green as a universal marker of solid tumours in patients.

The surgical resection of solid tumours can be enhanced by fluorescence-guided imaging. However, variable tumour uptake and incomplete clearance of fluorescent dyes reduces the accuracy of distinguishing tumour from normal tissue via conventional fluorescence intensity-based imaging. Here we show that, after systemic injection of the near-infrared dye indocyanine green in patients with various types of solid tumour, the fluorescence lifetime (FLT) of tumour tissue is longer than the FLT of non-cancerous tissue. This tumour-specific shift in FLT can be used to distinguish tumours from normal tissue with an accuracy of over 97% across tumour types, and can be visualized at the cellular level using microscopy and in larger specimens through wide-field imaging. Unlike fluorescence intensity, which depends on imaging-system parameters, tissue depth and the amount of dye taken up by tumours, FLT is a photophysical property that is largely independent of these factors. FLT imaging with indocyanine green may improve the accuracy of cancer surgeries.

Non-Invasive Assessment of Isocitrate Dehydrogenase-Mutant Gliomas Using Optimized Proton Magnetic Resonance Spectroscopy on a Routine Clinical 3-Tesla MRI.

PURPOSE: The isocitrate dehydrogenase (IDH) mutation has become one of the most important prognostic biomarkers in glioma management, indicating better treatment response and prognosis. IDH mutations confer neomorphic activity leading to the conversion of alpha-ketoglutarate (α-KG) to 2-hydroxyglutarate (2HG). The purpose of this study was to investigate the clinical potential of proton MR spectroscopy (1H-MRS) in identifying IDH-mutant gliomas by detecting characteristic resonances of 2HG and its complex interplay with other clinically relevant metabolites. MATERIALS AND METHODS: Thirty-two patients with suspected infiltrative glioma underwent a single-voxel (SVS, n = 17) and/or single-slice-multivoxel (1H-MRSI, n = 15) proton MR spectroscopy (1H-MRS) sequence with an optimized echo-time (97 ms) on 3T-MRI. Spectroscopy data were analyzed using the linear combination (LC) model. Cramér-Rao lower bound (CRLB) values of <40% were considered acceptable for detecting 2HG and <20% for other metabolites. Immunohistochemical analyses for determining IDH mutational status were subsequently performed from resected tumor specimens and findings were compared with the results from spectral data. Mann-Whitney and chi-squared tests were performed to ascertain differences in metabolite levels between IDH-mutant and IDH-wild-type gliomas. Receiver operating characteristic (ROC) curve analyses were also performed. RESULTS: Data from eight cases were excluded due to poor spectral quality or non-tumor-related etiology, and final data analyses were performed from 24 cases. Of these cases, 9/12 (75%) were correctly identified as IDH-mutant or IDH-wildtype gliomas through SVS and 10/12 (83%) through 1H-MRSI with an overall concordance rate of 79% (19/24). The sensitivity, specificity, positive predictive value, and negative predictive value were 80%, 77%, 86%, and 70%, respectively. The metabolite 2HG was found to be significant in predicting IDH-mutant gliomas through the chi-squared test (p < 0.01). The IDH-mutant gliomas also had a significantly higher NAA/Cr ratio (1.20 ± 0.09 vs. 0.75 ± 0.12 p = 0.016) and lower Glx/Cr ratio (0.86 ± 0.078 vs. 1.88 ± 0.66; p = 0.029) than those with IDH wild-type gliomas. The areas under the ROC curves for NAA/Cr and Glx/Cr were 0.808 and 0.786, respectively. CONCLUSIONS: Noninvasive optimized 1H-MRS may be useful in predicting IDH mutational status and 2HG may serve as a valuable diagnostic and prognostic biomarker in patients with gliomas.

The use of aprepitant for the prevention of postoperative nausea and vomiting in endoscopic transsphenoidal pituitary surgery.

BACKGROUND: Postoperative nausea and vomiting (PONV) are adverse effects after surgery, which may increase the risk of complications. Aprepitant is a neurokinin-1 receptor blocker and has been shown to reduce chemotherapy-related nausea and vomiting and PONV. However, its role in endoscopic skull base surgery remains unclear. The purpose of this study was to evaluate the effect of aprepitant in reducing PONV in endoscopic transsphenoidal (TSA) pituitary surgery. METHODS: A retrospective chart review between July 2021 and January 2023 of 127 consecutive patients who underwent TSA was performed at a tertiary academic institution. Patients were divided into 2 groups based on preoperative aprepitant use. Two groups were matched based on known risk factors of PONV (age, sex, nonsmoking, and history of PONV). The primary outcome was the incidence of PONV. Secondary outcome measures included the number of anti-emetic use, length of stay, and postoperative cererebrospinal fluid (CSF) leak. RESULTS: After matching, 48 patients were included in each group. The aprepitant group demonstrated a significantly lower incidence of vomiting than the non-aprepitant group (2.1% vs 22.9%, p = 0.002). The number of nausea episodes and anti-emetic use decreased with aprepitant use (p < 0.05). There was no difference in the incidence of nausea, length of stay, or postoperative CSF leak. Multivariate analysis demonstrated that aprepitant decreased the incidence of postoperative vomiting with odds ratio of 0.107. CONCLUSION: Aprepitant may serve as a useful preoperative treatment to reduce PONV in patients undergoing TSA. Further studies are needed to evaluate its impact in other arenas of endoscopic skull base surgery.

Intraoperative molecular imaging: 3rd biennial clinical trials update.

Significance: This third biennial intraoperative molecular imaging (IMI) conference shows how optical contrast agents have been applied to develop clinically significant endpoints that improve precision cancer surgery. Aim: National and international experts on IMI presented ongoing clinical trials in cancer surgery and preclinical work. Previously known dyes (with broader applications), new dyes, novel nonfluorescence-based imaging techniques, pediatric dyes, and normal tissue dyes were discussed. Approach: Principal investigators presenting at the Perelman School of Medicine Abramson Cancer Center's third clinical trials update on IMI were selected to discuss their clinical trials and endpoints. Results: Dyes that are FDA-approved or currently under clinical investigation in phase 1, 2, and 3 trials were discussed. Sections on how to move benchwork research to the bedside were also included. There was also a dedicated section for pediatric dyes and nonfluorescence-based dyes that have been newly developed. Conclusions: IMI is a valuable adjunct in precision cancer surgery and has broad applications in multiple subspecialties. It has been reliably used to alter the surgical course of patients and in clinical decision making. There remain gaps in the utilization of IMI in certain subspecialties and potential for developing newer and improved dyes and imaging techniques.

Orbital resection by intranasal technique (ORBIT): A new classification system for reporting endoscopically resectable primary benign orbital tumors.

BACKGROUND: The Cavernous Hemangioma Exclusively Endonasal Resection (CHEER) staging system has become the gold standard for outcomes reporting in endoscopic orbital surgery for orbital cavernous hemangiomas (OCHs). A recent systematic review demonstrated similar outcomes between OCHs and other primary benign orbital tumors (PBOTs). Therefore, we hypothesized that a simplified and more comprehensive classification system could be developed to predict surgical outcomes of other PBOTs. METHODS: Patient and tumor characteristics as well as surgical outcomes from 11 international centers were recorded. All tumors were retrospectively assigned an Orbital Resection by Intranasal Technique (ORBIT) class and stratified based on surgical approach as either exclusively endoscopic or combined (endoscopic and open). Outcomes based on approach were compared using chi-squared or Fisher's exact tests. The Cochrane-Armitage test for trend was used to analyze outcomes by class. RESULTS: Findings from 110 PBOTs from 110 patients (age 49.0 ± 15.0 years, 51.9% female) were included in the analysis. Higher ORBIT class was associated with a lower likelihood of gross total resection (GTR). GTR was more likely to be achieved when an exclusively endoscopic approach was utilized (p < 0.05). Tumors resected using a combined approach tended to be larger, to present with diplopia, and to have an immediate postoperative cranial nerve palsy (p < 0.05). CONCLUSION: Endoscopic treatment of PBOTs is an effective approach, with favorable short-term and long-term postoperative outcomes as well as low rate of adverse events. The ORBIT classification system is an anatomic-based framework that effectively facilitates high-quality outcomes reporting for all PBOTs.

Loss of RhoE Function in Dermatofibroma Promotes Disorganized Dermal Fibroblast Extracellular Matrix and Increased Integrin Activation.

Dermatofibromas (DFs) are common, benign fibrous skin tumors that can occur at any skin site. In most cases, DFs are solitary and sporadic, but a few are multiple and familial, and the mechanisms leading to these lesions are currently unclear. Using exome sequencing, we have identified a heterozygous variant in a pedigree with autosomal dominant multiple familial DF within RND3 (c.692C>T,p.T231M) that encodes for the small GTPase RhoE, a regulator of the actin cytoskeleton. Expression of T231M-RhoE or RhoE depletion using CRISPR in human dermal fibroblasts increased proliferation and adhesion to extracellular matrix through enhanced ß1 integrin activation and more disorganized matrix. The enzyme PLOD2 was identified as a binding partner for RhoE, and the formation of this complex was disrupted by T231M-RhoE. PLOD2 promotes collagen cross-linking and activation of ß1 integrins, and depleting PLOD2 in T231M-RhoE-expressing cells reduced T231M-RhoE-mediated ß1 integrin activation and led to increased matrix alignment. Immunohistochemical analysis revealed reduced expression of RhoE but increased expression of PLOD2 in the dermis of DF skin samples compared with that of the controls. Our data show that loss of RhoE function leads to increased PLOD2 activation, enhancing integrin activation and leading to a disorganized extracellular matrix, contributing to DF.

Implementation of a Streamlined Care Pathway to Reduce Cost and Length of Stay for Patients Undergoing Endoscopic Transsphenoidal Pituitary Surgery.

BACKGROUND: We implemented a streamlined care pathway for patients undergoing endoscopic transsphenoidal (TSA) pituitary surgery. Select patients are recovered in the postanesthesia care unit and transferred to a step-down unit for intermediate neurologic care (INCU), with clinicians trained to manage cerebrospinal fluid leak, diabetes insipidus (DI), and other complications. METHODS: We evaluated all TSA surgeries performed at 1 academic medical center from 7th January, 2017 to 30th March, 2020, collecting patient factors, tumor characteristics, cost variables, and outcomes. The INCU pathway was implemented on 7th January 2018. Pathway patients were compared with nonpathway patients across the study period. Outcomes were assessed using multivariate regression, adjusting for patient and surgical characteristics, including intraoperative cerebrospinal fluid leak, postoperative DI, and tumor dimensions. RESULTS: One hundred eighty-seven patients were identified. Seventy-nine were on the INCU pathway. Mean age was 53.5 years. Most patients were male (66%), privately insured (62%), and white (66%). Mean total cost of admission was $27,276. Mean length of stay (LOS) was 3.97 days. Use of the INCU pathway was associated with total cost reduction of $6376.33 (P < 0.001, 95% confidence interval [CI]: $3698.21-$9054.45) and LOS reduction by 1.27 days (P = 0.008, 95% CI: 0.33-2.20). In-hospital costs were reduced across all domains, including $1964.87 in variable direct labor costs (P < 0.001, 95% CI: $1142.08-$2787.64) and $1206.52 in variable direct supply costs (P < 0.001, 95% CI: $762.54-$1650.51). Pathway patients were discharged earlier despite a higher rate of postoperative DI (25% vs. 11%, P = 0.011), with fewer readmissions (0% vs. 6%, P = 0.021). CONCLUSIONS: A streamlined care pathway following TSA surgery can reduce in-hospital costs and LOS without compromising patient outcomes.