BACKGROUND: Current treatment guidelines for clival chordomas recommend surgical resection followed by high-dose radiotherapy (RT). However, in patients in whom gross total resection (GTR) is achieved, the benefits of additional RT remain unclear. OBJECTIVE: To investigate whether RT offers any benefit to progression-free survival (PFS) in patients undergoing GTR of clival chordoma by performing a systematic review of all currently published literature. METHODS: A total of 5 databases were searched to include all studies providing data on GTR ± RT for clival chordomas (January 1990-June 2021). Qualitative assessment was performed with Newcastle–Ottawa Scale guidelines for assessing quality of nonrandomized studies. Statistical analysis using individualized patient data of PFS was performed. RESULTS: The systematic search yielded 2979 studies, weaned to 22 full-text articles containing 108 patients. All patients underwent GTR of clival chordoma, with 46 (43%) patients receiving adjuvant RT. Mean PFS for RT patients was 31.09 months (IQR: 12.25-37.75) vs 54.92 months (IQR: 14.00-85.75) in non-RT patients. Overall, RT did not increase PFS (HR 0.320, P = .069) to a value that achieved statistical significance. Stratifying by photon therapy vs particle beam therapy yielded no statistically significant benefit for particle beam therapy for PFS (P = .300). Of patients with age ≥65 years, RT did not improve outcomes to statistical significance for PFS (HR 0.450, P = .481). Patients age ≥65 years had lower PFS on both bivariate analysis (HR 3.708, P = .007) and multivariate analysis (HR 3.322, P = .018). CONCLUSION: After achieving GTR of clival chordoma, fractionated RT offers unclear benefit upon survival outcomes.

The glymphatic system, or glial-lymphatic system, is a waste clearance system composed of perivascular channels formed by astrocytes that mediate the clearance of proteins and metabolites from the brain. These channels facilitate the movement of cerebrospinal fluid throughout brain parenchyma and are critical for homeostasis. Disruption of the glymphatic system leads to an accumulation of these waste products as well as increased interstitial fluid in the brain. These phenomena are also seen during and after subarachnoid hemorrhages (SAH), contributing to the brain damage seen after rupture of a major blood vessel. Herein this review provides an overview of the glymphatic system, its disruption during SAH, and its function in recovery following SAH. The review also outlines drugs which target the glymphatic system and may have therapeutic applications following SAH.

Craniopharyngiomas (CPs) are slow growing, histologically benign intracranial tumors located in the sellar–suprasellar region. Although known to have low mortality, their location and relationship to the adjacent neural structures results in patients having significant neurologic, endocrine, and visual comorbidities. The invasive nature of this tumor makes complete resection a challenge and contributes to its recurrence. Additionally, these tumors are bimodally distributed, being treated with surgery, and are followed by other adjuncts, such as focused radiation therapy, e.g., Gamma knife. Advances in surgical techniques, imaging tools, and instrumentations have resulted in the evolution of surgery using endoscopic techniques, with residual components being treated by radiotherapy to target the residual tumor. Advances in molecular biology have elucidated the main pathways involved in tumor development and recurrence, but presently, no other treatments are offered to patients, besides surgery, radiation, and endocrine management, as the disease and tumor evolve. We review the contemporary management of these tumors, from the evolution of surgical treatments, utilizing standard open microscopic approaches to the more recent endoscopic surgery, and discuss the current recommendations for care of these patients. We discuss the developments in radiation therapy, such as radiosurgery, being used as treatment strategies for craniopharyngioma, highlighting their beneficial effects on tumor resections while decreasing the rates of adverse outcomes. We also outline the recent chemotherapy modalities, which help control tumor growth, and the immune landscape on craniopharyngiomas that allow the development of novel immunotherapies.

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INTRODUCTION Our group and others have shown mRNA-vaccines have significant anti-tumor efficacy in the treatment of brain tumors and are currently being tested in first-in-human trials. To further enhance mRNA delivery, a hydrogel platform was developed with the addition of CXCL9 to promote immune cell trafficking. METHODS We generated the vaccine by utilizing a hydrogel platform. CXCL9 and Nano-mRNA were loaded into the hydrogel. In vitro recruitment of DCs and NK was evaluated by fluorescence microscopy. In vivo recruitment of immune cells was analyzed by flowcytometry after collecting the fat pad, spleen, and tumor samples from KR158b-luc and Gl261-gp100 tumor-bearing animals 3, 5 and 10 days after vaccine delivery. The efficacy of the vaccine was evaluated by measuring overall survival, and tumor growth was measured by IVIS live-imaging. RESULTS Dendritic cells(DCs) and natural killer(NK) cells were able to efficiently migrate within the hydrogel-CXCL9 platform and uptake and express mRNA in vivo. In vitro, the hydrogel-CXCL9 was combined with nanoparticles loaded with total tumor RNA, and the vaccine was delivered to KR-158-luc and GL261-gp100 tumor-bearing animals via mammary fat pad SQ injection. Flow cytometry of the fat pad and draining lymph nodes demonstrated showed significant recruitment of endogenous DCs including inflammatory-DC(P= 0.0035), conventional-DC1(P= 0.0076), pDC(P=0.0028), NK(p= 0.0025 compared to the control group. In two different tumor models, a single dose of the vaccine resulted in significant survival benefits compared to control animals (n=10,P< 0.0001). SQ injection was superior to intracranial injection of the vaccine. Vaccinated animals showed an increased number of antigen-specific CD8 T cells in spleen(P= 0.0001) and tumor-microenvironment(P= 0.0070). CONCLUSION The hydrogel-CXCL9 platform results in efficient delivery of mRNA loaded nanoparticles to endogenous DCs and also causes an upregulation of NK cells with resultant improved survival in murine GBM models including the highly resistant KR158 model with a single dose. Further studies are ongoing.

The breast is one of the common primary sites of brain metastases (BM). Radiotherapy for BM from breast cancer may include whole brain radiation therapy (WBRT), stereotactic radiosurgery (SRS), and stereotactic radiotherapy (SRT), but a consensus is difficult to reach because of the wide and varied protocols, indications, and outcomes of these interventions. Overall, dissemination of disease, patient functional status, and tumor size are all important factors in the decision of treatment with WBRT or SRS. Thus far, previous studies indicate that WBRT can improve tumor control compared to SRS, but increase side effects, however no randomized trials have compared the efficacy of these therapies in BM from breast cancer. Therapies targeting long non-coding RNAs and transcription factors, such as MALAT1, HOTAIR, lnc-BM, TGL1, and ATF3, have the potential to both prevent metastatic spread and treat BM with improved radiosensitivity. Given the propensity for HER2+ breast cancer to develop BM, the above-mentioned cell lines may represent an important target for future investigations, and the development of everolimus and pyrotinib are equally important.

BACKGROUND: Postoperative incisional negative pressure wound vacuum-assisted closure (VAC) dressings are being used as a primary dressing to optimize wound healing and help avoid complications of infection and dehiscence. Few studies have investigated whether application of VAC dressings on postoperative posterior spinal wounds can reduce the incidence of surgical site infections. OBJECTIVE: To describe our single-surgeon experience of using primary VAC after posterior spinal fusion (PSF) in a large sample of trauma patients. METHODS: This was an Institutional Review Board-approved retrospective comparative study and included all trauma patients presenting to our level 1 safety-net trauma center who required PSF and were operated on by the senior surgeon between 2016 and 2021. Primary outcomes were complications (surgical site infection, readmission for infection, and wound-related return to operating room [OR]) within 90 days after surgery. χ 2 testing and Student t testing were used to assess differences between treatment groups while bivariate and multivariate regression was performed for outcome assessment. RESULTS: Two hundred sixty-four patients met criteria and were included. One hundred fifty-seven (59%) were treated with standard dressing and 107 (41%) with VAC. Patients treated with VAC were more likely to be older (P = .015), have diabetes (P = .041), have an elevated body mass index (P = .020), and had more levels of fusion (P = .002). Despite this, presence of VAC was independently associated with decreased 90-day infection (hazard ratio = 0.397, P = .023) and decreased 90-day return to OR for woundrelated reasons (hazard ratio = 0.099, P = .031). CONCLUSION: Compared with the use of standard dressing, VAC was found to decrease surgical site infection and return to OR risk in trauma patients undergoing PSF.

Pallister-Hall syndrome (PHS) is an extremely rare genetic disorder for which the diagnosis is often overlooked. The objective of this case report is to highlight how clinical features used in conjunction with brain MRI findings can lead to an expeditious diagnosis without the need for invasive measures or genetic test results.We present the case of a three-day-old infant delivered at 34 and 4/7 weeks gestation who presented with mild respiratory distress and bilious emesis in the setting of an uncomplicated gestational course and vaginal delivery with no known teratogen exposure. A diagnosis of Pallister-Hall syndrome was made on the basis of physical exam findings, hormonal abnormalities and the identification of a hypothalamic hamartoma on brain MRI. The patient underwent multiple procedures for diagnosis and management of PHS complications, including a diverting jejunostomy for a long-segment Hirschsprung's and a laryngoscopy which identified a bifid epiglottis. The patient tolerated the interventions and did not have seizures on admission.The MRI brain detection of a hypothalamic hamartoma led to an earlier diagnosis of Pallister-Hall syndrome and thus further screening and identification of complications associated with this disorder were performed before genetic analyses or brain biopsies were obtained. Given the unique MRI features of hypothalamic hamartomas, brain MRI can be a useful tool for making an early PHS diagnosis when taken with clinical features concerning possible PHS.