The role of systemic therapy in advanced skull base chordomas: overview of the current state and the MD Anderson protocol.

The role of systemic therapy in primary or advanced and metastatic chordoma has been traditionally limited because of the inherent resistance to cytotoxic therapies and lack of specific or effective therapeutic targets. Despite resection and adjuvant radiation therapy, local recurrence rates in clival chordoma remain high and the risk of systemic metastases is not trivial, leading to significant morbidity and mortality. Recently, molecular targeted therapies (MTTs) and immune checkpoint inhibitors (ICIs) have emerged as promising therapeutic avenues in chordoma. In recent years, preclinical studies have identified potential targets based on intrinsic genetic dependencies, epigenetic modulators, or newly identified tumor-associated cell populations driving treatment resistance and recurrence. Nonetheless, the role of systemic therapies in the neoadjuvant or adjuvant setting for primary, locally progressive, and distant metastatic chordomas is still being investigated. Herein, an overview of current and emerging systemic treatment strategies in advanced clival chordoma is provided. Furthermore, several molecular biomarkers have been recently uncovered as potential predictors of the response to specific molecular therapeutics. The authors describe the recently discovered role of 1p36 and 9p21 deletions as biomarkers capable of guiding drug selection. Then they discuss completed and ongoing clinical trials of MTTs, including several tyrosine kinase inhibitors used as monotherapy or in combination, such as imatinib, sorafenib, dasatinib, and lapatinib, among others, as well as mammalian target of rapamycin inhibitors such as everolimus and rapamycin. They present their experience and other recent studies demonstrating vast benefits in advanced chordoma from ICIs. Additionally, they provide a brief overview of novel systemic strategies such as adoptive cell transfer (CAR-T and NK cells), oncolytic viruses, epigenetic targeting (KDM6, HDAC, and EZH2 inhibitors), and several promising preclinical studies with high translational potential. Finally, the authors present their institutional multidisciplinary protocol for the incorporation of systemic therapy for both newly diagnosed and recurrent chordomas based on molecular studies including upfront enrollment in MTT trials in patients with epidermal growth factor receptor upregulation or INI-1 deficiency or enrollment in ICI clinical trials for patients with high tumor mutational burden or high PD-L1 expression on tumor cells or in the tumor microenvironment.

Autologous rib graft for posterior cervical fusion in pediatric patients: efficacy and safety in the early postoperative period.

OBJECTIVE: The objective was to describe the indications, technique, and initial outcomes of autologous rib graft with recombinant human bone morphogenetic protein (rhBMP) in pediatric patients undergoing posterior cervical fusion. METHODS: A retrospective study was performed of all pediatric patients who underwent autologous rib grafting with extra-small rhBMP-2 for posterior craniocervical or cervical arthrodesis at a single institution between May 2020 and July 2023. Patients with less than 3 months of postoperative follow-up and no postoperative CT data were excluded. Primary outcomes included presence of fusion on CT, 30-day perioperative complications, and rib harvest complications. RESULTS: Twenty-eight sequential patients met inclusion criteria. Thirteen were male, 15 were female, and the average age was 9 years. There were no surgical site infections or instances of postoperative seroma or unplanned return to the operating room. All patients had solid fusion on postoperative CT at 3 months. The average follow-up was 14.5 months, with a range of 4 months to 3 years. There were no complications associated with the rib harvest, including no instances of harvest site pain, and all patient incisions healed well. CONCLUSIONS: The authors' preliminary results demonstrate that autologous rib graft with extra-small rhBMP-2 is an effective strategy to achieve a high rate of fusion in pediatric patients undergoing posterior instrumented craniocervical or cervical fusion. In this series, the authors found an acceptable safety profile, without seroma, surgical site infection, unplanned return to the operating room, or rib harvest complications.

Treatment of hydrocephalus following posterior fossa tumor resection: a multicenter collaboration from the Hydrocephalus Clinical Research Network.

OBJECTIVE: Persistent hydrocephalus following posterior fossa brain tumor (PFBT) resection is a common cause of morbidity in pediatric brain tumor patients, for which the optimal treatment is debated. The purpose of this study was to compare treatment outcomes between VPS and ETV in patients with persistent hydrocephalus following surgical resection of a PFBT. METHODS: A post-hoc analysis was performed of the Hydrocephalus Clinical Research Network (HCRN) prospective observational study evaluating VPS and ETV for pediatric patients. Children who experienced hydrocephalus secondary to PFBT from 2008 to 2021 were included. Primary outcomes were VPS/ETV treatment failure and time-to-failure (TTF). RESULTS: Among 241 patients, the VPS (183) and ETV (58) groups were similar in age, extent of tumor resection, and preoperative ETV Success Score. There was no difference in overall treatment failure between VPS and ETV (33.9% vs 31.0%, p = 0.751). However, mean TTF was shorter for ETV than VPS (0.45 years vs 1.30 years, p = 0.001). While major complication profiles were similar, compared to VPS, ETV patients had relatively higher incidence of minor CSF leak (10.3% vs. 1.1%, p = 0.003) and pseudomeningocele (12.1% vs 3.3%, p = 0.02). No ETV failures were identified beyond 3 years, while shunt failures occurred beyond 5 years. Shunt infections occurred in 5.5% of the VPS cohort. CONCLUSIONS: ETV and VPS offer similar overall success rates for PFBT-related postoperative hydrocephalus. ETV failure occurs earlier, while susceptibility to VPS failure persists beyond 5 years. Tumor histology and grade may be considered when selecting the optimal means of CSF diversion.

Patient, Disease, and Treatment-Related Factors Affecting Progression-Free and Disease-Specific Survival in Recurrent Chondrosarcomas of the Skull Base.

BACKGROUND: Recurrent skull base chondrosarcomas (CSA) are difficult to treat, and limited data are available to help guide subsequent therapy. OBJECTIVE: To further characterize the natural history of CSA and identify treatment modalities that were most effective in prolonging progression-free (PFS) and disease-specific survival (DSS). METHODS: We conducted a single-institution retrospective review of patients with recurrent skull base CSA from 1993 to 2021. Kaplan-Meier survival analyses for PFS and DSS were completed. Univariable and multivariable Cox proportional hazards regression models were used to identify patient-related, treatment-related, and disease-related factors that predicted PFS and DSS. RESULTS: A total of 28 patients and 84 episodes of recurrence were included. One-year PFS was 70.6%, 5-year PFS was 28.9%, and 10-year DSS was 78.5%. The median time to first progression was 23.9 months (range, 2.8-282 months). In univariable Cox proportional hazards regression, male sex, higher grade histology, fourth or greater progression episode status, distal pattern of recurrence, and treatment of recurrence without surgery or with chemotherapy alone predicted worse PFS. Multivariable regression predicted shortened DSS in male patients (hazard ratio [HR] 0.16; P = .021) and higher-grade tumors (HR 0.22; P = .039). Treatment of recurrence with surgery was associated with, but did not significantly predict, improved DSS (HR 1.78; P = .11). CONCLUSION: Several patient and disease-specific factors were associated with shorter PFS and DSS in recurrent skull base chondrosarcoma. For recurrences amenable to resection, surgery is recommended for treatment of recurrent CSA. Local recurrence management without surgery results in shorter PFS and DSS.

Robot-Assisted Deep Brain Stimulation: High Accuracy and Streamlined Workflow.

BACKGROUND: A number of stereotactic platforms are available for performing deep brain stimulation (DBS) lead implantation. Robot-assisted stereotaxy has emerged more recently demonstrating comparable accuracy and shorter operating room times compared with conventional frame-based systems. OBJECTIVE: To compare the accuracy of our streamlined robotic DBS workflow with data in the literature from frame-based and frameless systems. METHODS: We retrospectively reviewed 126 consecutive DBS lead placement procedures using a robotic stereotactic platform. Indications included Parkinson disease (n = 94), essential tremor (n = 21), obsessive compulsive disorder (n = 7), and dystonia (n = 4). Procedures were performed using a stereotactic frame for fixation and the frame pins as skull fiducials for robot registration. We used intraoperative fluoroscopic computed tomography for registration and postplacement verification. RESULTS: The mean radial error for the target point was 1.06 mm (SD: 0.55 mm, range 0.04-2.80 mm) on intraoperative fluoroscopic computed tomography. The mean operative time for an asleep, bilateral implant without implantable pulse generator placement was 238 minutes (SD: 52 minutes), and skin-to-skin procedure time was 116 minutes (SD: 42 minutes). CONCLUSION: We describe a streamlined workflow for DBS lead placement using robot-assisted stereotaxy with a comparable accuracy profile. Obviating the need for checking and switching coordinates, as is standard for frame-based DBS, also reduces the chance for human error and facilitates training.

Hemorrhagic cavum vergae colloid cyst: A presentation of anterograde amnesia without hydrocephalus.

Background: Colloid cysts characteristically arise from the roof of the third ventricle near the foramen of Monro, causing symptoms from obstructive hydrocephalus. However, atypical locations have been reported with various clinical presentations, growth patterns, and displacement of surrounding anatomic structures. Case Description: Here, we describe the interesting case of a patient with a large hemorrhagic cavum vergae colloid cyst presenting with anterograde amnesia soon after starting antiplatelet therapy. The patient did not have hydrocephalus on presentation and his amnesia persisted after complete removal of the hemorrhagic mass through transcallosal interforniceal approach. Conclusion: To the best of our knowledge, this is the only reported instance of a colloid cyst presenting with amnesia in the absence of hydrocephalus. Pathophysiology as well as diagnostic and management strategies of hemorrhagic colloid cysts are discussed.

Microsurgical Resection of Giant Thoraco-Lumbo-Sacral Ependymoma With Hybrid Spinal Reconstruction Using Multilevel Laminoplasty and Up-Front Thoracolumbar Posterior Fixation: 2-Dimensional Operative Video.

Extensive multifocal intradural lesions in children present a formidable challenge. This surgical video illustrates our management of a 14-yr=old boy with two intradural mass lesions on magnetic resonance imaging (MRI): one at T2-5 and the other from T12 through the sacral cul-de-sac. In a single procedure, we performed a T2-5 laminectomy and laminoplasty and T12-sacrum laminectomy for tumor resection. For reconstruction, we performed complete laminoplasty at all levels with supplementation at the thoracolumbar junction via T11-L2 posterior spinal fixation and allograft placement for fusion. In this video, we illustrate the microsurgical challenges of intradural tumor resection in both the thoracic cord and amidst the cauda equina. In young patients, prevention of postsurgical spinal deformity is of paramount concern. We discuss considerations for long-segment spinal stabilization in an adolescent and describe our decision-making to perform stabilization at the thoracolumbar junction to supplement laminoplasty while preserving function. The patient and their family consented to the procedure. Image of the article at 0:51 is from McGirt et al, Short-term progressive spinal deformity following laminoplasty versus laminectomy for resection of intradural spinal tumors: analysis of 239 patients, Neurosurgery, 2010, 66(5), 1005-1012, by permission of the Congress of Neurological Surgeons.

Surgical treatment of common peroneal neuropathy in schwannomatosis: illustrative cases.

BACKGROUND: Neurofibromatosis syndromes such as neurofibromatosis type 1, neurofibromatosis type 2, and schwannomatosis often result in painful symptoms related to tumor burden. OBSERVATIONS: Painful symptoms classically associated with common points of peripheral nerve entrapment, such as common peroneal neuropathy at the fibular tunnel, may present in patients both with and without focal tumor involvement. LESSONS: Surgical decompression at the point of entrapment, with or without resection of tumor, may provide symptomatic relief. Examples of surgical decompression at the point of entrapment, both with and without resection of tumor, are presented.

Neurostimulation for treatment-resistant posttraumatic stress disorder: an update on neurocircuitry and therapeutic targets.

Posttraumatic stress disorder (PTSD) is a widespread and often devastating psychiatric condition. Core symptoms include intrusive and distressing thoughts, heightened reactivity, mood changes, cognitive impairments, and consequent avoidance of trauma-related stimuli. Symptoms of PTSD are often refractory to standard treatments, and neuromodulatory techniques have therefore drawn significant interest among the most treatment-resistant patients. Transcranial magnetic stimulation has demonstrated minimal efficacy, and deep brain stimulation trials are currently ongoing. PTSD is a disorder of neural circuitry; the current understanding includes involvement of the amygdala (basolateral and central nuclei), the prefrontal cortex (ventral medial and dorsolateral regions), and the hippocampus. Neuroimaging and optogenetic studies have improved the understanding of large-scale neural networks and the effects of microcircuitry manipulation, respectively. This review discusses the current PTSD literature and ongoing neurostimulation trials, and it highlights the current understanding of neuronal circuit dysfunction in PTSD. The authors emphasize the anatomical correlations of PTSD's hallmark symptoms, offer another potential deep brain stimulation target for PTSD, and note the need for continued research to identify useful biomarkers for the development of closed-loop therapies. Although there is hope that neuromodulation will become a viable treatment modality for PTSD, this concept remains theoretical, and further research should involve institutional review board-approved controlled prospective clinical studies.

Practical Application of Recent Advances in Diagnostic, Prognostic, and Therapeutic Modalities for Spinal Cord Injury.

OBJECTIVE: Spinal cord injury remains a highly morbid entity, with limited treatment modalities in both acute and chronic settings. Clinical research efforts to improve therapeutic guidelines are confounded by initial evaluation inaccuracies, as presentations are frequently complicated by trauma and objective diagnostic and prognostic methods are poorly defined. The purpose of our study was to review recent practical advances for further delineation of these injuries and how such classification may benefit the development of novel treatments. METHODS: A review was carried out of recent studies reported within the last 5 years for prognostic and diagnostic modalities of acute spinal cord injury. RESULTS: Substantial efforts have been made to improve the timeliness and accuracy of the initial assessment, not only for the purpose of enhancing prognostication but also in determining the efficacy of new treatments. Whether it be applying traumatic brain injury principles to limit injury extent, external stimulators used for chronic pain conditions to enhance the effects of physical therapy, or creative algorithms incorporating various nerve or muscle transfer techniques, innovative and practical solutions continue to be developed in lieu of definitive treatment. Further development will benefit from enhanced stratification of injury from accurate and practical assessment modalities. CONCLUSIONS: Recent advances in accurate, timely, and practical classification methods of acute spinal cord injury will assist in the development of novel treatment approaches for both acute and chronic injury alike.

Pituitary Adenoma and Craniopharyngioma Collision Tumor: Diagnostic, Treatment Considerations, and Review of the Literature.

BACKGROUND: Different diseases may occur within the same anatomic space and invade one another. Lesions of this nature are described as collision tumors. Collision tumors of the sella are rare, with pituitary adenoma-craniopharyngiomas having been described in only 15 cases. We discuss common and rare lesions of the sellar region, their neurodiagnostic qualities, and treatment considerations. CASE DESCRIPTION: We present the case of a 49-year-old woman presenting with symptoms of headache and blurred vision who underwent a 2-stage procedure and was found to have a craniopharyngioma and corticotrophic pituitary adenoma in collision. We review the literature on various combinations of sellar collision lesions, noting diagnostic and treatment considerations. Neuroimaging, intraoperative pathology, and histologic review help to provide optimum treatment when unusual conditions of the sella arise. CONCLUSIONS: Many mechanisms for the development of collision lesions have been theorized, and further investigation may provide definitive answers regarding the origin of these neoplastic entities.

Supracerebellar Infratentorial Endoscopic and Endoscopic-Assisted Approaches to Pineal Lesions: Technical Report and Review of the Literature.

The pineal gland has a deep central location, making it a surgeon's no man's land. Surgical pathology within this territory presents a unique challenge and an opportunity for employment of various surgical techniques. In modern times, the microsurgical technique has been competing with the endoscope for achieving superior surgical results. We describe two cases utilizing a purely endoscopic and an endoscopic-assisted supracerebellar infratentorial approach in accessing lesions of the pineal gland. We also discuss our early learning experience with these approaches.

Assessment of the Nurse Medication Administration Workflow Process.

This paper presents findings of an observational study of the Registered Nurse (RN) Medication Administration Process (MAP) conducted on two comparable medical units in a large urban tertiary care medical center in Columbia, South Carolina. A total of 305 individual MAP observations were recorded over a 6-week period with an average of 5 MAP observations per RN participant for both clinical units. A key MAP variation was identified in terms of unbundled versus bundled MAP performance. In the unbundled workflow, an RN engages in the MAP by performing only MAP tasks during a care episode. In the bundled workflow, an RN completes medication administration along with other patient care responsibilities during the care episode. Using a discrete-event simulation model, this paper addresses the difference between unbundled and bundled workflow and their effects on simulated redesign interventions.

Assessment of the Nurse Medication Administration Workflow Process

This paper presents findings of an observational study of the Registered Nurse (RN) Medication Administration Process (MAP) conducted on two comparable medical units in a large urban tertiary care medical center in Columbia, South Carolina. A total of 305 individual MAP observations were recorded over a 6-week period with an average of 5 MAP observations per RN participant for both clinical units. A key MAP variation was identified in terms of unbundled versus bundled MAP performance. In the unbundled workflow, an RN engages in the MAP by performing only MAP tasks during a care episode. In the bundled workflow, an RN completes medication administration along with other patient care responsibilities during the care episode. Using a discrete-event simulation model, this paper addresses the difference between unbundled and bundled workflow and their effects on simulated redesign interventions.

Surgical Adhesive Drape (IO-ban) as Postoperative Surgical Site Dressing.

STUDY DESIGN: Retrospective chart analysis. OBJECTIVE: The objective of this study is to describe the senior author's (MNN) experience applying a widely available surgical drape as a postoperative sterile surgical site dressing for both cranial and spinal procedures. SUMMARY OF BACKGROUND DATA: Surgical site infection (SSI) is an important complication of spine surgery that can result in significant morbidity. There is wide variation in wound care management in practice, including dressing type. Given the known bactericidal properties of the surgical drape, there may be a benefit of continuing its use immediately postoperatively. METHODS: All of the senior author's cases from September 2014 through September 2015 were reviewed. These were contrasted to the previous year prior to the institution of a sterile surgical drape as a postoperative dressing. RESULTS: Only one surgical case out of 157 operative interventions (35 cranial, 124 spinal) required operative debridement due to infection. From September 2013 to September 2014, prior to the institution of a sterile surgical drape as dressing, the author had five infections out of 143 operations (46 cranial, 97 spinal) requiring intervention. CONCLUSION: The implementation of a sterile surgical drape as a closed postoperative surgical site dressing has led to a decrease in surgical site infections. The technique is simple and widely available, and should be considered for use to diminish surgical site infections.

Effective healthcare process redesign through an interdisciplinary team approach.

Healthcare process redesign is a complex and often high risk undertaking. Typically, there is a limited understanding of the baseline process and often inadequate tools by which to assess it. This can be confounded by narrow redesign team expertise that can result in unanticipated and/or unintended redesign consequences. Interdisciplinary research teams of healthcare, biostatistics, engineering and computer science experts provide broad support for a more effective and safer approach to healthcare process redesign. We describe an interdisciplinary research team focused on medication administration process (MAP)redesign and its achievements and challenges.

Linking nurse characteristics, team member effectiveness, practice environment, and medication error incidence.

Clinical unit nurse characteristics, practice environment, and team member effectiveness are assumed to play a critical role in medication safety. This study used a multimethod approach to examine the association of these factors with medication errors. Findings suggested that older, more experienced registered nurses made less medication errors. Environment and team member effectiveness were not strongly associated with medication error incidence. Numerous system factors limited implementation and outcomes of this safety study and are discussed.

A model for medication safety event detection.

BACKGROUND: Hospital medication safety event detection predominantly emphasizes the identification of preventable adverse drug events (ADEs) through self-reports. These relatively rare events only provide insight into patient harm and self-reports identify only a small portion of ADEs. A broader system-focused approach to medication safety event detection that uses an array of event detection methods is recommended. This approach illuminates medication system deficits and supports improvement strategies that can prevent future patient risk. OBJECTIVE: To: (i) describe a system-focused approach to hospital medication safety event detection, and (ii) present a case illustration of approach application. SYSTEM-FOCUSED MODEL AND METHODOLOGY: A three-level medication safety event detection model that ranges from a narrow harm-focused to broader system-focused approach is described. A standardized cross-level methodology to detect medication safety events is presented. CASE ILLUSTRATION: A Level 3 system-focused methodology that incorporated both voluntary and non-voluntary event detection strategies was used in 17 critical care (n = 4), intermediate care (n = 7) and medical-surgical units (n = 6) across two hospitals. A total of 431 events were detected: 78 (18.1%) ADEs and 353 (81.9%) potential ADEs. Of the 353 PADEs, 302 (70.0%) were non-intercepted events. Non-voluntary detection methods yielded the majority of events (367, 85.1%). CONCLUSIONS: The incidence of ADEs was low when compared with non-intercepted PADEs. This was indicative of medication safety system failures that placed patients at risk for potential harm. Non-voluntary detection methods were much more effective at detecting events than traditional self-report methods.