Surgeon-led improvement in compliance with use of sequential compression devices in a neurosurgery patient population.

INTRODUCTION: Sequential compression devices (SCDs) are the mainstay of mechanical prophylaxis for venous thromboembolism in perioperative neurosurgical patients and are especially crucial when chemical prophylaxis is contraindicated. OBJECTIVES: This study aimed to characterise and improve SCD compliance in neurosurgery stepdown patients. METHODS: SCD compliance in a neurosurgical stepdown unit was tracked across 13 months (August 2022-August 2023). When not properly functioning, the missing element was documented. Compliance was calculated daily in all patients with SCD orders, and then averaged monthly. Most common barriers to compliance were identified. With nursing, we implemented a best practice alert to facilitate nursing education at month 3 and tracked compliance over 9 months, with two breaks in surveillance. At month 12, we implemented a patient-engagement measure through creating and distributing a patient-directed infographic and tracked compliance over 2 months. RESULTS: Compliance averaged 19.7% (n=95) during August and 38.4% (n=131) in September. After implementing the best practice alert and supply chain upgrades, compliance improved to 48.8% (n=150) in October, 41.2% (n=104) in March and 45.9% (n=76) in April. The infographic improved compliance to 51.4% (n=70) in July and 55.1% (n=34) in August. Compliance was significantly increased from baseline in August to October (z=4.5838, p<0.00001), sustained through March (z=3.2774, p=0.00104) and further improved by August (z=3.9025, p=0.0001). CONCLUSION: Beyond an initial Hawthorne effect, implementation of the best practice nursing alert facilitated sustained improvement in SCD compliance despite breaks in surveillance. SCD compliance nonetheless remained below 50% until implementation of patient-engagement measures which were dependent on physician involvement.

Intraoperative Closed Reduction of Traumatic Lateraloptosis: Operative Nuances.

BACKGROUND AND IMPORTANCE: Traumatic lateral spondyloptosis, or lateraloptosis, is the complete lateral dislocation of the spine. Reduction in these dislocations presents unique challenges, especially in cases of preserved neurological function. Open techniques carry significant risks of cerebrospinal fluid leak and neurological injury. For traditional spondyloptosis, off-table closed techniques have been described but may result in loss of the reduction when the patient is transferred to the operative table. An on-table closed reduction technique has potential advantages over previously described open reduction or off-table techniques for the treatment of lateraloptosis. CLINICAL PRESENTATION: The authors describe an on-table closed reduction technique for lateraloptosis, presenting an illustrative case in which the technique was applied. This technique is compared with alternative open and off-table reduction techniques described in the literature. The patient had good mechanical and neurological outcomes. At 14 months postoperatively, she is neurologically intact, back to work involving heavy lifting, and has only moderate back pain. CONCLUSION: On-table closed reduction before open fixation should be considered in cases of lateraloptosis, particularly when there is preserved neurological function.

The Carotid Sinus Nerve and the First English Translation of Hering's Original Research on this Nerve.

This paper provides a brief depiction of the life and achievements of the most iconic experiments of Heinrich Ewald Hering. The authors herein have presented a translation of his paper on the carotid sinus nerve in English; the original paper by Heinrich Ewald Hering, titled "Ueber die Wand des Sinus caroticus als Reizempfänger und den Sinusnerv als zentripetale Bahn für die Sinusreflexe" (1924), provides a detailed account of his experimental process and findings. He recognized that the sinus reflexes are mediated by a branch of the glossopharyngeal nerve (CN IX).

Intraventricular metastases from rectal carcinoma: case report and literature review.

Intraventricular metastases are a rare occurrence, particularly from a primary colorectal malignancy. To our knowledge, this is the first report of intraventricular metastasis from rectal cancer. A 72-year-old male presented with a new diagnosis of multiple intraventricular lesions, an anterior mediastinal mass and a rectal mass. His workup revealed rectal adenocarcinoma with intraventricular metastases and an incidental thymoma. Ommaya reservoir placement was performed via an awake procedure rather than under general anesthesia due to airway concerns. Cerebrospinal fluid (CSF) cytology was positive for malignancy and consistent with adenocarcinoma. Two weeks postoperatively, the patient underwent whole brain radiation. Although rare, this diagnosis should always be considered in the differential for solitary or multiple intraventricular lesions. CSF sampling is a useful alternative to intraventricular biopsy for diagnosis of intraventricular metastases. Awake placement of Ommaya reservoir is a safe option in the management of patients with intraventricular metastases, especially those who cannot undergo general anesthesia.

Trepanation in Ancient China.

Trepanation, the process of making a burr hole in the skull to access the brain, is an ancient form of a primitive craniotomy. There is widespread evidence of contributions made to this practice by ancient civilizations in Europe, Africa, and South America, where archaeologists have unearthed thousands of trepanned skulls dating back to the Neolithic period. Little is known about trepanation in China, and it is commonly believed that the Chinese used only traditional Chinese medicine and nonsurgical methods for treating brain injuries. However, a thorough analysis of the available archeological and literary evidence reveals that trepanation was widely practiced throughout China thousands of years ago. A significant number of trepanned Chinese skulls have been unearthed showing signs of healing and suggesting that patients survived after surgery. Trepanation was likely performed for therapeutic and spiritual reasons. Medical and historical works from Chinese literature contain descriptions of primitive neurosurgical procedures, including stories of surgeons, such as the legendary Hua Tuo, and surgical techniques used for the treatment of brain pathologies. The lack of translation of Chinese reports into the English language and the lack of publications on this topic in the English language may have contributed to the misconception that ancient China was devoid of trepanation. This article summarizes the available evidence attesting to the performance of successful primitive cranial surgery in ancient China.

Stem cells and gliomas: past, present, and future.

The recognition of stem cells (SC) in the adult CNS and in association with gliomas has spawned an entire field of research and intense investigation. A large body of knowledge is being accumulated to gain insight into the pathobiology of gliomas with the intent of finally improving the grave prognosis that continues to beset patients with high grade gliomas (HGG). In this article, we provide a historical overview of the events leading to the discovery of SC and glioma stem cells (GSC). We then focus on the current understanding of GSC with respect to markers, clinical significance, and their targeting. We discuss current data and developments using SC as vehicles to delivery therapeutic agents to HGG. We conclude with a discussion of opportunities for future development and concepts aimed at reducing tumor recurrence and improving survival for patients with HGG.

Resection of Primary Brachial Plexus Tumor via a Modified Supraclavicular Approach.

Benign peripheral nerve sheath tumors are generally considered curable lesions, and surgical resection is recommended as the primary line of treatment. When these tumors occur in the brachial plexus, they are most frequently accessed via the supraclavicular approach. Traditional descriptions of this approach have included either transection of sternocleidomastoid (SCM) muscle fibers or disarticulation of the clavicular head of the SCM muscle. This report presents a simple and easy-to-adapt modification of the supraclavicular approach that offers greater preservation of the SCM muscle. The modification primarily consists of the creation of an intramuscular window between the sternal and clavicular heads of the SCM via the splitting and dilation SCM muscle fibers. This technique minimizes the disruption of SCM muscle tissue compared with previous descriptions and may be associated with improved postoperative pain and return to function.

Significance of interleukin-13 receptor alpha 2-targeted glioblastoma therapy.

Glioblastoma multiforme (GBM) remains one of the most lethal primary brain tumors despite surgical and therapeutic advancements. Targeted therapies of neoplastic diseases, including GBM, have received a great deal of interest in recent years. A highly studied target of GBM is interleukin-13 receptor α chain variant 2 (IL13Rα2). Targeted therapies against IL13Rα2 in GBM include fusion chimera proteins of IL-13 and bacterial toxins, nanoparticles, and oncolytic viruses. In addition, immunotherapies have been developed using monoclonal antibodies and cell-based strategies such as IL13Rα2-pulsed dendritic cells and IL13Rα2-targeted chimeric antigen receptor-modified T cells. Advanced therapeutic development has led to the completion of phase I clinical trials for chimeric antigen receptor-modified T cells and phase III clinical trials for IL-13-conjugated bacterial toxin, with promising outcomes. Selective expression of IL13Rα2 on tumor cells, while absent in the surrounding normal brain tissue, has motivated continued study of IL13Rα2 as an important candidate for targeted glioma therapy. Here, we review the preclinical and clinical studies targeting IL13Rα2 in GBM and discuss new advances and promising applications.

Characterization of fenofibrate-mediated anti-proliferative pro-apoptotic effects on high-grade gliomas and anti-invasive effects on glioma stem cells.

Glioblastoma is the most common, and at the same time, most aggressive type of high-grade glioma (HGG). The prognosis of glioblastoma patients treated with standard therapy including surgery, temozolomide and radiation therapy remains poor. Peroxisome proliferator-activated receptor-α (PPARα) agonists are in widespread clinical use for the treatment of hyperlipidemia. Recent evidence has suggested a potential role in various cancers including glioblastoma. In this study, we characterized the effects of PPARα agonist, fenofibrate, directly on HGG cells and glioma stem cells (GSC). Fenofibrate exhibited dose-dependent p53-independent anti-proliferative effects on HGG starting at 25 µM and pro-apoptotic effects starting at 50 µM, suggesting that the anti-proliferative actions are present only at 25 µM. PPARα was expressed in all HGG cell lines. Inhibition of PPARα with specific inhibitor GW6471 did not affect either proliferation or apoptosis suggesting that these are PPARα-independent effects. Fenofibrate treatment of HGG cells robustly diminished the expression of key signaling pathways, including NF-κB and cyclin D1. Phosphorylation of Akt was also diminished, with no change in total Akt. Effects on apoptotic signaling molecules, Bax and Bcl-xL, had a trend towards pro-apoptotic effects. With respect to GSC, fenofibrate treatment at 25 µM significantly decreased invasion in association with a decrease in CD133 and Oct4 expression. Overall, results support consideration of fenofibrate as an anti-glioma agent and establish its potential as an adjunct treatment strategy for HGG. Translation to the clinical setting could be rapid given its current use as a clinical agent and its low toxicity profile.

Radiosurgery for high-grade glioma.

BACKGROUND: For patients with newly diagnosed high-grade gliomas (HGG), the current standard-of-care treatment involves surgical resection, followed by concomitant temozolomide (TMZ) and external beam radiation therapy (XRT), and subsequent TMZ chemotherapy. For patients with recurrent HGG, there is no standard of care. Stereotactic radiosurgery (SRS) is used to deliver focused, relatively large doses of radiation to a small, precisely defined target. Treatment is usually delivered in a single fraction, but may be delivered in up to five fractions. The role of SRS in the management of patients with HGG is not well established. METHODS: The PubMed database was searched with combinations of relevant MESH headings and limits. Case reports and/or small case series were excluded. Attention was focused on overall median survival as an objective measure, and data were examined separately for newly diagnosed and recurrent HGG. RESULTS: With respect to newly diagnosed HGG, there is strong evidence that addition of an SRS boost prior to standard XRT provides no survival benefit. However, recent retrospective evidence suggests a possible survival benefit when SRS is performed after XRT. With respect to recurrent HGG, there is suggestion that SRS may confer a survival benefit but with potentially higher complication rates. Newer studies are investigating the combination of SRS with targeted molecular agents. Controlled prospective clinical trials using advanced imaging techniques are necessary for a complete assessment. CONCLUSIONS: SRS has the potential to provide a survival benefit for patients with HGG. Further research is clearly warranted to define its role in the management of newly diagnosed and recurrent HGG.

Stemness of the CT-2A Immunocompetent Mouse Brain Tumor Model: Characterization In Vitro.

Evidence has pointed to brain tumor stem cells (BTSC) as culprits behind human high-grade glioma (hHGG) resistance to standard therapy. Pre-clinical rodent models are the mainstay for testing of new therapeutic strategies. The typical model involves the intracranial injection of human glioma cells into immunocompromised hosts, hindering the evaluation of tumor-host responses and resulting in non-infiltrative tumors. The CT-2A model is an immunocompetent mouse model with potential to overcome these disadvantages. In this study, we confirmed the highly infiltrative nature of intracranial CT-2A tumors and optimized reproducible injection parameters. We then generated neurospheres and established, for the first time, the stemness of this model. CT-2A expression of the BTSC marker, CD133, increased from 2% in monolayer cells to 31% in fully-formed neurospheres. Investigation of three stem cell markers (Oct4, Nanog and Nestin) revealed a distinct stemness signature with monolayer cells expressing Oct4 and Nestin (no Nanog), and neurospheres expressing all three. Additionally, CT-2A cells were more proliferative and invasive than U87 cells, while CT-2A neurospheres were significantly more proliferative and invasive than either monolayer cells in vitro. Taken together, our results show that this model is a valuable tool for pre-clinical testing of novel therapeutics against hHGG and also affords the opportunity for investigation of BTSC in an immunocompetent setting.

Stem cells as therapeutic vehicles for the treatment of high-grade gliomas.

Stem cells have generated great interest in the past decade as potential tools for cell-based treatment of human high-grade gliomas. Thus far, 3 types of stem cells have been tested as vehicles for various therapeutic agents: embryonic, neural, and mesenchymal. The types of therapeutic approaches and/or agents examined in the context of stem cell-based delivery include cytokines, enzyme/prodrug suicide combinations, viral particles, matrix metalloproteinases, and antibodies. Each strategy has specific advantages and disadvantages. Irrespective of the source and/or type of stem cell, there are several areas of concern for their translation to the clinical setting, such as migration in the adult human brain, potential teratogenesis, immune rejection, and regulatory and ethical issues. Nonetheless, a clinical trial is under way using neural stem cell-based delivery of an enzyme/prodrug suicide combination for recurrent high-grade glioma. A proposed future direction could encompass the use of stem cells as vehicles for delivery of agents targeting glioma stem cells, which have been implicated in the resistance of high-grade glioma to treatment. Overall, stem cells are providing an unprecedented opportunity for cell-based approaches in the treatment of high-grade gliomas, which have a persistently dismal prognosis and mandate a continued search for therapeutic options.

Targeting glioma stem cells: a novel framework for brain tumors.

The past decade has seen a dramatic increase in stem cell research that focuses on glioma stem cells (GSC) and their mechanisms of action, revealing multiple potential targets for primary malignant brain tumors. Herein, we present a novel framework for considering GSC targets based on direct and indirect strategies. Direct strategies target GSC molecular pathways to overcome their resistance to radiation and chemotherapy, block their function or induce their differentiation. Indirect strategies target the microenvironment of the GSC, namely the perivascular, hypoxic and immune niches. Progress made on GSC targets is reviewed in detail and specific pathways are identified in context of the proposed framework. The potential barriers for translation to the clinical setting are also discussed. Overall, targeting GSC provides an unprecedented opportunity for revolutionary approaches to treat high-grade gliomas that continue to have a poor patient prognosis.

Hemangiopericytoma: collision with meningioma and recurrence.

Intracranial hemangiopericytomas are a rare type of primary brain tumor, representing only about 0.5% of all primary brain tumors. Even more rare is the co-existence of two juxtaposed primary brain tumors, termed a "collision" tumor. This report provides the first documentation in the literature of a hemangiopericytoma colliding with a meningioma, and recurring after treatment with gross total resection. Surgical samples were fully evaluated with hematoxylin and eosin and reticulin staining, as well as immunohistochemical analysis. Results were classically representative of a hemangiopericytoma (World Health Organization grade II) and of a meningioma (World Health Organization grade I). This report of a unique collision tumor not only augments the repertoire of collision tumor combinations described in literature but also provides follow-up on the clinical outcome of the patient, thereby raising clinically relevant issues ranging from presentation to treatment paradigms.

Gene therapy as an adjuvant treatment for malignant gliomas: from bench to bedside.

Malignant brain tumors, including high-grade gliomas, are among the most lethal of all cancers. Despite considerable advances, including multi-modality treatments with surgery, radiotherapy, and chemotherapy, the overall prognosis for patients with this disease remains dismal. Currently available treatments necessitate the development of more effective tumor-selective therapies. The use of gene therapy for brain tumor therapy is promising as it can be delivered in situ and selectively targets brain tumor cells while sparing the adjacent normal brain tissue. In this article, we summarize the laboratory and clinical work using viral, cell-based, and synthetic vectors, as well as other strategies focused on potentiate gene delivery. Although tangible results on patients' survival remains to be further documented, significant advances in therapeutic gene transfer strategies have been made. The enthusiasm of this progress needs to be tempered by the realistic assessment of the challenges needed to be overcome. Finally, as the field of gene delivery progresses, advances must be made in identifying genes and proteins key to the treatment of malignant gliomas. Due to the great heterogeneity of malignant glioma cells, only approaches combining different strategies may be ultimately successful in defeating this disease.

Dose response of the AIA rabbit stifle joint to boron neutron capture synovectomy.

This study assessed the treatment with boron neutron capture synovectomy of synovitis in the antigen-induced arthritis (AIA) model. A boron compound, potassium dodecahydrododeca-borate (K(2)B(12)H(12)), was injected into stifle joints of 24 AIA and 12 normal rabbits and activated by neutron bombardment of the joint to achieve doses from 800 to 81,000 RBE-cGy. Synovial ablation in the AIA joint was accomplished at doses of 6,000 to 7,000 RBE-cGy with no adverse effects to skin or extracapsular tissues.

Clinical uses and misuses of dehydroepiandrosterone.

Dehydroepiandrosterone is the most abundant adrenal androgen and also functions as a neurosteroid. Serum concentrations decline with age and can serve as a prognostic factor in both critical illnesses and breast cancer progression. Evidence is accruing in support of dehydroepiandrosterone supplementation in adrenal insufficiency, hypopituitarism, osteoporosis, systemic lupus erythematosus, depression and schizophrenia. Research is ongoing at both the basic and the clinical level to elucidate mechanisms of action and establish efficacy and safety, as well as to expand new areas of potential application for this multi-faceted hormone.