Cytotoxic activity has been reported for the xanthone α-mangostin (AMN) against Glioblastoma multiforme (GBM), an aggressive malignant brain cancer with a poor prognosis. Recognizing that AMN’s high degree of hydrophobicity is likely to limit its systemic administration, we formulated AMN using reconstituted high-density lipoprotein (rHDL) nanoparticles. The photophysical characteristics of the formulation, including fluorescence lifetime and steady-state anisotropy, indicated that AMN was successfully incorporated into the rHDL nanoparticles. To our knowledge, this is the first report on the fluorescent characteristics of AMN with an HDL-based drug carrier. Cytotoxicity studies in a 2D culture and 3D spheroid model of LN-229 GBM cells and normal human astrocytes showed an enhanced therapeutic index with the rHDL-AMN formulation compared to the unincorporated AMN and Temozolomide, a standard GBM chemotherapy agent. Furthermore, treatment with the rHDL-AMN facilitated a dose-dependent upregulation of autophagy and reactive oxygen species generation to a greater extent in LN-229 cells compared to astrocytes, indicating the reduced off-target toxicity of this novel formulation. These studies indicate the potential therapeutic benefits to GBM patients via selective targeting using the rHDL-AMN formulation.

The primary focus of this review is lipoprotein-based drug carriers, more specifically, high-density lipoprotein (HDL) type nanoparticles (NPs). These nanostructures are discussed regarding their suitability for clinical applications, particularly for cancer therapy. Poor solubility and insufficient capability to selectively target malignant tumors represent significant challenges facing many anticancer drugs. Nevertheless, we and others have found that most, if not all, of these difficulties, can be overcome by incorporating drugs into lipoprotein nanocarriers1. While not a novel approach, as HDL type NPs have been documented to deliver anticancer agents to cancer cells effectively and tumors2,3,4,5, including those that, on their own (without facilitation), exhibited less than desirable therapeutic efficacy6, due to their desirable features (see below), HDL type drug carriers, at least in our view, hold tremendous promise as facilitators of cancer chemotherapy. One of the key aspects of the HDL-type NP-facilitated drug transport is the receptor-mediated uptake of the payload from the NPs7,8. Consequently, in this review, major emphasis is placed on monitoring the expression of the scavenger receptor type B1 (SR-B1) as a potentially valuable tool for the pre-treatment selection of patients regarding their suitability for advanced, personalized chemotherapy. The main emphasis in this article is on developing novel cancer therapeutics, while approaches for treating other diseases via lipoprotein nanocarriers are briefly discussed.

BACKGROUND Transverse myelitis is a rare neurological occurrence with varied presentation. Imaging is necessary to properly diagnose this condition; however, identifying the cause of this condition may often be difficult. OBSERVATIONS An otherwise healthy patient presented to the clinic with peculiar neurological symptoms without an obvious underlying cause. Imaging evidenced no significant structural defects but did lead to discovery of cord enhancement compatible with a diagnosis of transverse myelitis. Corticosteroid treatment was initiated rapidly to address this pathology, and the patient recovered without deficits. To identify the underlying cause, patient medical history was reviewed thoroughly and compared with existing literature. Previous tuberculosis infection could be a less likely cause of the neurological symptoms. However, recent vaccination with the Johnson & Johnson coronavirus disease 2019 (COVID-19) vaccine could be a more likely cause of the transverse myelitis, which has been rarely reported. LESSONS Transverse myelitis after COVID-19 infection has been an escalating phenomenon. However, transverse myelitis after COVID-19 vaccination is a rare occurrence that is also on the rise. Given the increased rates of vaccination, transverse myelitis should not be overlooked as a potential pathology, due to the severity of neurological impairment if this condition is not treated rapidly.

Branched-chain amino acids (BCAAs) are known to be neurorestorative after traumatic brain injury (TBI). Despite clinically significant improvements in severe TBI patients given BCAAs after TBI, the approach is largely an unrecognized option. Further, TBI continues to be the most common cause of morbidity and mortality in adolescents and adults. To date, no study has evaluated whether BCAAs can be preventive or neuroprotective if taken before a TBI. We hypothesized that if BCAAs were elevated in the circulation before TBI, the brain would readily access the BCAAs and the severity of injury would be reduced. Before TBI induction with a standard weight-drop method, 50 adult mice were randomized into groups that were shams, untreated, and pre-treated, post-treated, or pre- + post-treated with BCAAs. Pre-treated mice received BCAAs through supplemented water and were dosed by oral gavage 45 min before TBI induction. All mice underwent beam walking to assess motor recovery, and the Morris water maze assessed cognitive function post-injury. On post-injury day 14, brains were harvested to assess levels of astrocytes and microglia with glial fibrillary acidic protein (GFAP) and ionized calcium-binding adapter molecule 1 (IBA-1) immunohistochemistry, respectively. Pre-treated and pre- +post-treated mice exhibited significantly better motor recovery and cognitive function than the other groups. The pre- + post-treated group had the best overall memory performance, whereas the pre-treated and post-treated groups only had limited improvements in memory compared to untreated animals. Pre- + post-treated brains had levels of GFAP that were similar to the sham group, whereas the pre-only and post-only groups showed increases. Although trends existed, no meaningful changes in IBA-1 were detected. This is the first study, animal or human, to demonstrate that BCAA are neuroprotective and substantiates their neurorestorative benefits after TBI, most likely through the important roles of BCAAs to glutamate homeostasis.

BACKGROUND Cervical radiculopathy is a common cause of neck pain, with radiation into the upper extremity in a dermatomal pattern. Corticosteroid injection is a conservative management option with a low risk of major adverse events. No reviewed literature or case reports have implicated phrenic nerve injury secondary to cervical transforaminal epidural steroid injection (CTFESI). OBSERVATIONS A 45-year-old man with severe right C6 radiculopathy secondary to a large right-sided C5–6 herniated intervertebral disc presented to the pain management clinic, where he received a right-sided C6 CTFESI. An hour after injection, the patient experienced shortness of breath, which was found to be caused by right diaphragmatic paralysis. The patient underwent a C5–6 anterior cervical discectomy and fusion, which provided complete relief of his radicular symptoms. However, the right hemidiaphragmatic paralysis remained at the 1-year postoperative visit. LESSONS Thorough literature review showed no established explanations for phrenic nerve injury after CTFESI. In this study, the authors explored the suspected mechanisms of possible injury to the phrenic nerve. Epidural corticosteroid injection is considered to be a safe option for conservative management of cervical radiculopathy. This study unveiled a unique and important adverse event that should be considered before a patient receives CTFESI.

PURPOSE:The goal of these studies was to provide proof of concept for a novel targeted therapy for Glioblastoma Multiforme (GBM). Methods. These studies involve the evaluation of reconstituted high density lipoprotein (rHDL) nanoparticles (NPs) as delivery agents for the drug, mammalian Target of Rapamycin (mTOR) inhibitor Everolimus (EVR) to GBM cells. Cytotoxicity studies and assessment of downstream effects, including apoptosis, migration, and cell cycle events, were probed, in relation to the expression of scavenger receptor B type 1 (SR-B1) by GBM cells.RESULTS:Findings from cytotoxicity studies indicate that the rHDL/EVR formulation was 185 times more potent than free EVR against high SR-B1 expressing cell line (LN 229). Cell cycle analysis revealed that rHDL/EVR treated LN229 cells had a 5.8 times higher apoptotic cell population than those treated with EVR. The sensitivity of GBM cells to EVR treatment was strongly correlated with SR-B1 expression.CONCLUSIONS:These studies present strong proof of concept regarding the efficacy of delivering EVR and likely other agents, via a biocompatible transport system, targeted to the SR-B1 receptor that is upregulated in most cancers, including GBM. Targeting the SR-B1 receptor could thus lead to effective personalized therapy of GBM.

"Letter to the Editor. Reversal of low prealbumin with oral branched-chain amino acids: a simple solution to an expensive problem" published on 26 Oct 2018 by American Association of Neurological Surgeons.

Ventral calcified meningiomas of the upper thoracic spine provide a unique challenge due to their location. The posterior approach has long been utilized for resection of ventral meningiomas with high success rates and low morbidity. There are a number of anatomical factors that can increase the difficulty in the case including patient body habitus, calcified tumors ventrally located can be adherent to the cord or anterior spinal artery, angle of the ribs and the vascularity in and around the tumor. We present a very challenging case of a large ventral calcified meningioma at T4 in a patient with body mass index of 50 (5′6, 337lbs) who presented with progressive paraplegia.

Surgical site infections in neurosurgery patients are increasing due to the high rates of trauma cases, increase in patient comorbidities, and the prevalence of multi-resistant drug organisms. Recent reports have demonstrated that topical antibiotic powder used during wound closure significantly decreases rates of wound infections in spine cases. The authors present a prospective study of 102 consecutive cranial or spinal neurosurgery cases. A mixture of 1 gram Vancomycin powder mixed with 1 gram of hydrolyzed or activated collagen powder (CellerateRX Surgical) was then placed within the incision. This was followed by skin closure with either staples or subcuticular sutures. Patients were seen at approximately 2 weeks postoperatively for incision check and subsequent removal of sutures or staples. In conclusion, this study demonstrated that the combination of activated collagen (CellerateRX Surgical) and Vancomycin powder resulted in no infections or wound dehiscence. The hygroscopic nature of the activated collagen bound the aqueous vancomycin to the activated collagen retaining and prolonging the antimicrobial environment in the surgical site.

Dear Editor, We read with interest “Surgical approach to cervical spondylotic myelopathy on the basis of radiological patterns of compression: prospective analysis of 129 cases” by Bapat et al. [1]. There are several studies attempting to elucidate the most appropriate approach in the treatment of myelopathic patients with multilevel cervical spondylosis [2–9]. Bapat et al. [1] divided the patients into four different categories based on the radiographic appearance of cord compression and basically analyzed the adage “treat anterior pathology anteriorly and posterior pathology posteriorly”. We found the study design appropriate for radiographic divisions of patients; however, it has been demonstrated that surgical outcomes in cervical myelopathy are dependent on more than just the approach. Several studies are worth the discussion: Yamazaki et al. [4] reviewed cervical myelopathy in patients of varying ages and determined that the preoperative radiographic transverse area of the spinal cord, at the level of maximum compression, may be a reliable predictor of recovery in both younger and elderly patient groups; furthermore the length of symptom duration was a significant factor in the elderly. A recent landmark study by Shamji et al. revealed that clinical myelopathy augments the rates of complication during cervical fusion, regardless of the approach. Shamji et al. [3] went on to state that “the exclusion of pathoanatomical data prevents any conclusions being drawn about the merits and disadvantages of anterior versus posterior surgery”. Posterior decompressive surgery for cervical myelopathy secondary to cervical spondylosis is strongly supported in the literature [2, 5–9]. Houten and Cooper [2] demonstrated that multilevel laminectomy and lateral mass fusion were associated with minimal morbidity, provided excellent decompression and precluded further development of spondylosis at fused levels in comparison to anterior surgery. We, along with other studies, reported years ago that dorsal migration of the spinal cord is often not appreciated by many surgeons and if one performs an adequate decompression, the spinal cord will migrate [7–9]. Levi et al. [8] performed extensive cervical laminectomies on patients suffering a central cord syndrome from spondylosis and demonstrated that the spinal cord does migrate dorsally after extensive laminectomy. In closing, we support the study by Bapat et al. and found their results interesting, however, we want to caution the readers that might accept this generalized conclusion that “anterior approach is superior to posterior” based on the experimental design of four radiographic groups. Cervical myelopathy is very complex and outcomes are dependent on multiple variables. We are very strong advocates of posterior decompression with lateral mass fusions in patients with multilevel degenerative cervical spondylotic myelopathy and obviously approach each patient based on their individual pathoanatomy.

In Brief Study Design. Retrospective analysis of patients whom underwent one-level anterior lumbar interbody fusion or posterior lumbar interbody fusion with percutaneous pedicle screws. Objective. To determine which minimally invasive fusion technique, anterior or posterior lumbar fusions, induces the least amount of muscle damage. Summary of Background Data. Creatine phosphokinase is recognized as a good marker for muscle damage occurring in patients after spine surgery. Minimally invasive fusions are known to reduce the amount of muscle damage. Which surgery induces the least amount of muscle damage is yet to be determined. Minimally invasive spine surgery is becoming increasing popular due to the benefits of less muscle damage, shorter hospital length and quicker recovery. Lumbar fusions are one of the most common surgeries and is becoming less invasive with the use of percutaneous pedicle screws. Methods. Seventy-four patients whom underwent either anterior or posterior lumbar interbody fusions with percutaneous pedicle screws had preoperative and postoperative creatine kinase levels. Statistical analysis then compared the average change between the 2 groups. Results. Minimally invasive anterior lumbar interbody fusions with percutaneous pedicle screws had significantly less muscle damage (P < 0.05) than minimally invasive posterior lumbar interbody fusions with percutanoues screws. Conclusion. Minimally invasive anterior lumbar interbody fusions with percutaneous pedicle screws cause significantly less muscle damage than minimally invasive posterior lumbar interbody fusions with percutaneous screws. Furthermore minimally invasive anterior lumbar body interbody fusions demonstrated near the same amount of muscle damage to previously published literature on lumbar microdikectomies. Minimally invasive spine surgery is becoming more common with numerous techniques. Anterior and posterior lumbar spine fusion has been modified to minimally invasive approaches with percutaneous screws. A comparative study on the amount of muscle damage suffered with these minimally invasive fusions was performed to determine which technique is least invasive.

Study Design. Retrospective analysis of patients whom underwent one-level anterior lumbar interbody fusion or posterior lumbar interbody fusion with percutaneous pedicle screws. Objective. To determine which minimally invasive fusion technique, anterior or posterior lumbar fusions, induces the least amount of muscle damage. Summary of Background Data. Creatine phosphokinase is recognized as a good marker for muscle damage occurring in patients after spine surgery. Minimally invasive fusions are known to reduce the amount of muscle damage. Which surgery induces the least amount of muscle damage is yet to be determined. Minimally invasive spine surgery is becoming increasing popular due to the benefits of less muscle damage, shorter hospital length and quicker recovery. Lumbar fusions are one of the most common surgeries and is becoming less invasive with the use of percutaneous pedicle screws. Methods. Seventy-four patients whom underwent either anterior or posterior lumbar interbody fusions with percutaneous pedicle screws had preoperative and postoperative creatine kinase levels. Statistical analysis then compared the average change between the 2 groups. Results. Minimally invasive anterior lumbar interbody fusions with percutaneous pedicle screws had significantly less muscle damage (P < 0.05) than minimally invasive posterior lumbar interbody fusions with percutanoues screws. Conclusion. Minimally invasive anterior lumbar interbody fusions with percutaneous pedicle screws cause significantly less muscle damage than minimally invasive posterior lumbar interbody fusions with percutaneous screws. Furthermore minimally invasive anterior lumbar body interbody fusions demonstrated near the same amount of muscle damage to previously published literature on lumbar microdikectomies.

The authors describe 4 cases of delayed dural laceration by hydroxyapatite (HA) spacer causing tetraparesis following double-door laminoplasty. There are few reports of iatrogenic spinal cord lesions developing after double-door laminoplasty, although some complications such as postoperative C-5 paralysis or axial symptoms have been reported. The purpose of this report is to draw attention to the possibility of delayed dural laceration and its triggering mechanism.One hundred thirty patients treated for cervical myelopathy were followed up for an average of 2 years and 9 months after laminoplasty.Four patients experienced aggravation of cervical myelopathy. Anterior dislodgement of HA spacers was shown on plain lateral radiographs. Follow-up T2-weighted magnetic resonance imaging demonstrated that the dislodged HA spacers were surrounded by cerebrospinal fluid at the time of aggravation. The dislodged HA spacers were removed and the dural membrane defects were repaired by patching with the fascia of the gluteus maximus muscle. The preoperative symptoms improved after the second operation in all patients.It is hypothesized that the loosening of the HA spacer in split spinous processes could occur with the movement of the cervical spine and/or the breakage of the suture before bone bonding. Anterior dislodgement of the HA spacer toward the spinal canal would cause dural laceration by direct friction between the dural membrane and the dislodged HA spacer, resulting in clinical aggravation. Despite the well-documented advantages of using HA spacers for double-door laminoplasty, possible laceration due to a dislodged HA spacer should be considered as a late complication.

The present invention relates to novel human BMP polypeptides and isolated nucleic acids containing the coding regions of the genes encoding such polypeptides. Also provided are vectors, host cells, antibodies, and recombinant methods for producing human BMP polypeptides. The invention further relates to diagnostic and therapeutic methods useful for diagnosing and treating disorders related to these novel human BMP polypeptides.

The authors describe 4 cases of delayed dural laceration by hydroxyapatite (HA) spacer causing tetraparesis following double-door laminoplasty. There are few reports of iatrogenic spinal cord lesions developing after double-door laminoplasty, although some complications such as postoperative C-5 paralysis or axial symptoms have been reported. The purpose of this report is to draw attention to the possibility of delayed dural laceration and its triggering mechanism.One hundred thirty patients treated for cervical myelopathy were followed up for an average of 2 years and 9 months after laminoplasty.Four patients experienced aggravation of cervical myelopathy. Anterior dislodgement of HA spacers was shown on plain lateral radiographs. Follow-up T2-weighted magnetic resonance imaging demonstrated that the dislodged HA spacers were surrounded by cerebrospinal fluid at the time of aggravation. The dislodged HA spacers were removed and the dural membrane defects were repaired by patching with the fascia of the gluteus maximus muscle. The preoperative symptoms improved after the second operation in all patients.It is hypothesized that the loosening of the HA spacer in split spinous processes could occur with the movement of the cervical spine and/or the breakage of the suture before bone bonding. Anterior dislodgement of the HA spacer toward the spinal canal would cause dural laceration by direct friction between the dural membrane and the dislodged HA spacer, resulting in clinical aggravation. Despite the well-documented advantages of using HA spacers for double-door laminoplasty, possible laceration due to a dislodged HA spacer should be considered as a late complication.