Patient Characteristics Associated with Sexual Interest and Activity Among Adults with Spina Bifida.

OBJECTIVE: To identify factors associated with sexual interest and activity among adults with spina bifida and to describe the sexual profile of those who were sexually active. Sexual health of adults with spina bifida is often neglected and current knowledge on the topic is limited. METHODS: An anonymous web-based survey was advertised and administered between March 2018 and September 2018 and participants 16 years and older with spina bifida were included in this study. Respondents were asked about sexual interest, activity, and function using the validated Patient-Reported Outcomes Measurement Information System Sexual Function Profile. Bivariate and multivariable models with ordinal logistic regression were fitted to evaluate predictors of sexual interest and sexual function. RESULTS: Of the 261 respondents with a self-reported diagnosis of spina bifida (mean age of 38.5 years), 73.2% noted at least a little bit of interest in sexual activity. In multivariate analysis, women were less likely to report higher sexual interest than men (odds ratio (OR) = 0.53, 95% CI 0.31-0.92, P = .03) whereas those with higher physical functioning were more likely to have higher sexual interest (OR = 1.04, confidence interval (CI) 1.01-1.07, P = .03). Just less than half of respondents (46.4%) were sexually active in the past 30 days, and those with a ventriculoperitoneal shunt were less likely to engage in sexual activity compared to those without (OR = 0.36, 95% CI 0.19-0.68; P <.01). CONCLUSION: The mismatch between sexual interest and sexual activity highlights the importance of exploring issues related to sexual health when counseling adult patients with spina bifida.

Large Variations in the Prices of Urologic Procedures at Academic Medical Centers 1 Year After Implementation of the Price Transparency Final Rule.

Importance: Patients with urologic diseases often experience financial toxicity, defined as high levels of financial burden and concern, after receiving care. The Price Transparency Final Rule, which requires hospitals to disclose both the commercial and cash prices for at least 300 services, was implemented to facilitate price shopping, decrease price dispersion, and lower health care costs. Objective: To evaluate compliance with the Price Transparency Final Rule and to quantify variations in the price of urologic procedures among academic hospitals and by insurance class. Design, Setting, and Participants: This was a cross-sectional study that determined the prices of 5 common urologic procedures among academic medical centers and by insurance class. Prices were obtained from the Turquoise Health Database on March 24, 2022. Academic hospitals were identified from the Association of American Medical Colleges website. The 5 most common urologic procedures were cystourethroscopy, prostate biopsy, laparoscopic radical prostatectomy, transurethral resection of the prostate, and ureteroscopy with laser lithotripsy. Using the corresponding Current Procedural Terminology codes, the Turquoise Health Database was queried to identify the cash price, Medicare price, Medicaid price, and commercial insurance price for these procedures. Exposures: The Price Transparency Final Rule, which went into effect January 1, 2021. Main Outcomes and Measures: Variability in procedure price among academic medical centers and by insurance class (Medicare, Medicaid, commercial, and cash price). Results: Of 153 hospitals, only 20 (13%) listed a commercial price for all 5 procedures. The commercial price was reported most often for cystourethroscopy (86 hospitals [56%]) and least often for laparoscopic radical prostatectomy (45 hospitals [29%]). The cash price was lower than the Medicare, Medicaid, and commercial price at 24 hospitals (16%). Prices varied substantially across hospitals for all 5 procedures. There were significant variations in the prices of cystoscopy (χ23 = 85.9; P = .001), prostate biopsy (χ23 = 64.6; P = .001), prostatectomy (χ23 = 24.4; P = .001), transurethral resection of the prostate (χ23 = 51.3; P = .001), and ureteroscopy with laser lithotripsy (χ23 = 63.0; P = .001) by insurance type. Conclusions and Relevance: These findings suggest that, more than 1 year after the implementation of the Price Transparency Final Rule, there are still large variations in the prices of urologic procedures among academic hospitals and by insurance class. Currently, in certain situations, health care costs could be reduced if patients paid out of pocket. The Centers for Medicare & Medicaid Services may improve price transparency by better enforcing penalties for noncompliance, increasing penalties, and ensuring that hospitals report prices in a way that is easy for patients to access and understand.

Impact of Age and Symptom Development on SARS-CoV-2 Transmission in Households With Children-Maryland, New York, and Utah, August 2020-October 2021.

Background: Households are common places for spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We investigated factors associated with household transmission and acquisition of SARS-CoV-2. Methods: Households with children age <18 years were enrolled into prospective, longitudinal cohorts and followed from August 2020 to August 2021 in Utah, September 2020 to August 2021 in New York City, and November 2020 to October 2021 in Maryland. Participants self-collected nasal swabs weekly and with onset of acute illness. Swabs were tested for SARS-CoV-2 using reverse transcription polymerase chain reaction. We assessed factors associated with SARS-CoV-2 acquisition using a multilevel logistic regression adjusted for household size and clustering and SARS-CoV-2 transmission using a logistic regression adjusted for household size. Results: Among 2053 people (513 households) enrolled, 180 people (8.8%; in 76 households) tested positive for SARS-CoV-2. Compared with children age <12 years, the odds of acquiring infection were lower for adults age ≥18 years (adjusted odds ratio [aOR], 0.34; 95% CI, 0.14-0.87); however, this may reflect vaccination status, which protected against SARS-CoV-2 acquisition (aOR, 0.17; 95% CI, 0.03-0.91). The odds of onward transmission were similar between symptomatic and asymptomatic primary cases (aOR, 1.00; 95% CI, 0.35-2.93) and did not differ by age (12-17 years vs <12 years: aOR, 1.08; 95% CI, 0.20-5.62; ≥18 years vs <12 years: aOR, 1.70; 95% CI, 0.52-5.83). Conclusions: Adults had lower odds of acquiring SARS-CoV-2 compared with children, but this association might be influenced by coronavirus disease 2019 (COVID-19) vaccination, which was primarily available for adults and protective against infection. In contrast, all ages, regardless of symptoms and COVID-19 vaccination, had similar odds of transmitting SARS-CoV-2. Our findings underscore the importance of SARS-CoV-2 mitigation measures for persons of all ages.

Combining locoregional CAR-T cells, autologous + allogeneic tumor lysate vaccination and levamisole in treatment of glioblastoma.

Glioblastoma multiforme (GBM) is an aggressive brain malignancy and harbors a microenvironment limiting immune cells activity. CAR-T cells are being tested in the treatment of cancers and there exist reports which demonstrate dramatic regression of multicentric GBMs following intrathecal treatment with CAR-T cells. In this article, a triple approach for immune treatment of GBM is proposed. First, GBM tumor specimens for each patient will be saved and cultured to obtain tumor lysates. Then, levamisole will be applied, which possesses immunostimulating, anti-glycolytic, and anti-angiogenic features. Following priming the immune system, GBM patients will be injected with lysates of their own tumor cells plus lysates from a GBM cell line, U251. After 3 months of this treatment, CAR-T cells (transduced with IL13Rα2-CAR) will be applied via intratumoral approach. As such, genetically-modified and native immunocytes may 'meet' in the vicinity of deeply-invading tumor cells and demonstrate greater efficacy via cell-cell interactions. By this, a self-propagating cyclic process - a cancer-immunity cycle - may be initiated to eradicate cancer cells.

MGMT in glial carcinogenesis. Roles from prevention to treatment.

Many investigations exist regarding the effect of the DNA repair enzyme MGMT (O 6 -methylguanine- DNA-methyltransferase)-encoding gene methylation on the antineoplasticity of temozolomide in glioblastoma patients. However, there exist surprisingly lesser studies regarding the associations between MGMT enzyme biochemistry with glial carcinogenesis. MGMT involves in risk of malignancies associated with ionizing radiation, smoking, exposure to polycyclic aromatic hydrocarbons, chlorinated solvents, vinylchloride and hairdyes. All these factors are also proposed to link with gliomagenesis, yet MGMT interactions with these carcinogens in gliomagenesis are not studied yet. In future, MGMT sequencing may be employed in vulnerable populations working in industries associated with exposure to these carcinogens to develop preventive strategies. Given that MGMT is involved in DNA repair, a polymorphism may simultaneously modify the risk of gliomas while enhancing temozolomide cytotoxicity in both marrow and tumor cells.

Operative Outcomes After Cervical Diffuse Idiopathic Skeletal Hyperostosis Fracture in the Elderly.

BACKGROUND: Cervical diffuse idiopathic skeletal hyperostosis (DISH) fractures are frequently unstable and carry significant risk of neurologic injury and death. Most patients with DISH fractures are elderly (>70 years) with significant comorbidities. We assessed factors that contribute to outcomes in elderly patients with cervical DISH fractures. METHODS: Elderly patients with cervical DISH fractures from 2008 to 2017 were included in this retrospective multi-institutional cohort study. Predictor variables included injury level, surgical approach, preinjury comorbidities, American Society of Anesthesiologists (ASA) score, American Spinal Injury Association (ASIA) impairment scale grade, preoperative anticoagulation status, and the subaxial cervical spine injury classification system (SLIC) score. Univariate and multivariate analyses were utilized to identify factors associated with 30-day mortality and ambulatory status at discharge. RESULTS: A total of 48 patients, mean age 74.7 years old (range 60-96), underwent cervical fixation for DISH fractures. Average SLIC score was 6.30 ± 1.2 (range 5-8), and most frequent fracture level was at C6 to -C7 (31.3%) followed by C7-T1 (25.0%). Forty (83.3%) patients underwent posterior fixation, 7 (14.6%) with anterior fixation, and 1 (2.1%) had combined approach. Ten (20.4%) patients died within 30 days of surgery. Multivariate analysis demonstrated that poorer preoperative ASIA grade (OR 2.35, P = 0.003, CI = 1.33-4.14) and ASA score >3 (P = 0.027) had increased risk of being nonambulatory at discharge. Higher SLIC score was associated with increased 30-day mortality (P = 0.021, CI = 1.20-9.60). CONCLUSIONS: Cervical DISH fractures can be highly unstable, for which instrumentation and fixation are indicated. Surgical decision-making should focus on preoperative ASIA grade, SLIC score, and ASA score. CLINICAL RELEVANCE: The study is relevant due to an aging poulation predisposed to cervical DISH fractures.

A hypothetical proposal to employ meperidine and tamoxifen in treatment of glioblastoma. Role of P-glycoprotein, ceramide and metabolic pathways.

Meperidine (pethidine) is a µ-opioid receptor (MOR) agonist widely used in the treatment of cancer pain. While MOR agonists in experimental models have demonstrated both pro- and antitumorigenic properties, meperidine has unique features which may be predominantly anticancer in nature. Meperidine both inhibits NMDA (N-methyl-D-Aspartate) receptors, which are involved in the progression of glioblastoma, and blocks NADH:Ubiquinone Oxidoreductase, which may hinder mitochondrial respiration. In the developing embryonic neural tissue, meperidine reduces cell proliferation around the neural tube and lowers the expression of the B RE (brain and reproductive organ-expressed). This is notable given that the B RE gene is implicated in cancer chemoresistance and gliomagenesis. Further, meperidine inhibits P-glycoprotein, which is involved in cancer multidrug resistance and the degradation of the sphingolipid backbone, ceramide. By enhancing the pro-autophagic and pro-apoptotic ceramide levels in cancer cells, meperidine stimulates cell death and reverses multidrug resistance. Tamoxifen, a safe medication employed in the treatment of breast cancer, directly blocks P-glycoprotein and boosts levels of ceramide both via inhibition of glycosylceramide synthase and ceramidase. Further, tamoxifen blocks NMDA-neurotoxicity and therefore it may act synergistically with meperidine in reducing glioblastoma progression associated with NMDA-activation. Finally, tamoxifen blocks glycolysis which may enhance the mitochondrial-blocking activity of meperidine to shut down energy metabolism of glioblastoma cells. Because of these properties, we believe that the combination of meperidine and tamoxifen merits study in cell culture and animal models to investigate a potential synergistic relationship in the treatment of glioblastoma.

Outcomes of Vesicourethral Anastomotic Stenosis and Bladder Neck Contracture With Direct Visual Internal Urethrotomy With Mitomycin-C After Prostate Cancer Treatment.

OBJECTIVE: To examine the use of Direct Visual Internal Urethrotomy with Mitomycin-C (DVIU-MMC) for bladder neck contracture and vesicourethral anastomotic stenosis in men who have undergone treatment for prostate cancer with radical prostatectomy and/or radiation therapy. METHODS: Retrospective chart review of patients at a tertiary care center who underwent DVIU-MMC for recurrent bladder neck contracture/vesicourethral anastomotic stenosis between 2012 and 2020. Patients with complete urethral obliteration, prior bladder neck reconstruction, or less than 3 months of follow-up were excluded. Patients were sorted into three groups based on prostate cancer treatment history: radical prostatectomy (RP), RP with subsequent external beam radiation therapy (RP-EBRT), and radiation therapy (RT). RESULTS: Fifty-one patients with a median follow up of 32 months were included. Twenty-nine percent had pre-operative suprapubic tube (SPT), Foley, or required clean intermittent catheterization. Overall success after initial DVIU-MMC was 45%. In all patients with up to four procedures, cumulative overall success was 84%. There was no significant difference in relative success rates between groups. However, the interval to recurrence after initial DVIU-MMC was shortest for RP-EBRT group (P = .018). Three patients required SPT, all were in the RP-EBRT group. There was no statistical difference in recurrence after any number of procedures between patients in radiation (RP-EBRT and RT) and non-radiation (RP) groups. CONCLUSION: There was no significant difference in success rates between patients who had undergone RP-EBRT, RT, or RP. However, our data suggests that RP-EBRT patients experience poorer outcomes given that their interval to recurrence was more rapid and all patients requiring SPT placement were in this group.

Incidence Rates, Household Infection Risk, and Clinical Characteristics of SARS-CoV-2 Infection Among Children and Adults in Utah and New York City, New York.

Importance: Data about the risk of SARS-CoV-2 infection among children compared with adults are needed to inform COVID-19 risk communication and prevention strategies, including COVID-19 vaccination policies for children. Objective: To compare incidence rates and clinical characteristics of SARS-CoV-2 infection among adults and children and estimated household infection risks within a prospective household cohort. Design, Setting, and Participants: Households with at least 1 child aged 0 to 17 years in selected counties in Utah and New York City, New York, were eligible for enrollment. From September 2020 through April 2021, participants self-collected midturbinate nasal swabs for reverse transcription-polymerase chain reaction testing for SARS-CoV-2 and responded to symptom questionnaires each week. Participants also self-collected additional respiratory specimens with onset of COVID-19-like illness. For children unable to self-collect respiratory specimens, an adult caregiver collected the specimens. Main Outcomes and Measures: The primary outcome was incident cases of any SARS-CoV-2 infection, including asymptomatic and symptomatic infections. Additional measures were the asymptomatic fraction of infection calculated by dividing incidence rates of asymptomatic infection by rates of any infection, clinical characteristics of infection, and household infection risks. Primary outcomes were compared by participant age group. Results: A total of 1236 participants in 310 households participated in surveillance, including 176 participants (14%) who were aged 0 to 4 years, 313 (25%) aged 5 to 11 years, 163 (13%) aged 12 to 17 years, and 584 (47%) 18 years or older. Overall incidence rates of SARS-CoV-2 infection were 3.8 (95% CI, 2.4-5.9) and 7.7 (95% CI, 4.1-14.5) per 1000 person-weeks among the Utah and New York City cohorts, respectively. Site-adjusted incidence rates per 1000 person-weeks were similar by age group: 6.3 (95% CI, 3.6-11.0) for children 0 to 4 years, 4.4 (95% CI, 2.5-7.5) for children 5 to 11 years, 6.0 (95% CI, 3.0-11.7) for children 12 to 17 years, and 5.1 (95% CI, 3.3-7.8) for adults (≥18 years). The asymptomatic fractions of infection by age group were 52%, 50%, 45%, and 12% among individuals aged 0 to 4 years, 5 to 11 years, 12 to 17 years, and 18 years or older, respectively. Among 40 households with 1 or more SARS-CoV-2 infections, the mean risk of SARS-CoV-2 infection among all enrolled household members was 52% (range, 11%-100%), with higher risks in New York City compared with Utah (80% [95% CI, 64%-91%] vs 44% [95% CI, 36%-53%]; P < .001). Conclusions and Relevance: In this study, children had similar incidence rates of SARS-CoV-2 infection compared with adults, but a larger proportion of infections among children were asymptomatic.

Large Variation in International Prescribing Rates of Opioids After Robotic Prostatectomy.

OBJECTIVE: To compare international opioid prescribing patterns for patients undergoing robotic assisted laparoscopic prostatectomy. To our knowledge, this is the first study to assess international opioid prescribing trends among urologists. METHODS: An anonymous Web-based survey assessing the frequency and quantity of opioid prescriptions for robotic assisted laparoscopic prostatectomy was designed using Qualtrics software. The survey was distributed to urologists internationally via Twitter and email in early 2021. Prescribing patterns were analyzed based on country of practice in three groups: United States, Canada, and all other countries. RESULTS: 160 participants from 26 countries completed the survey including the United States (51%), Greece (19%), Canada (9%), Israel (3.1%). The percentage of providers prescribing post-discharge opioids significantly differed between Canada, the United States, and other countries (86%, 63%, and 11%, respectively, P <.0001). There was a significant difference between years of experience in those who provide opioids compared to those who do not (8 years vs 5 years, P = .0004). The average morphine milligram equivalents (MME) provided in those who did prescribe opioids was greatest in the United States but was not significantly different between groups (mean MME: United States 58 mg, Canada 46 mg, all others 54 mg; P = .63). Attending physicians prescribed more MME than trainees (residents, fellows) on average (attending mean MME = 75 mg, trainee mean MME = 40 mg, P = .017). CONCLUSION: Opioid prescriptions after robotic assisted prostatectomy are common in North America and used sparingly in the rest of the world.

Does Patient Sex Affect Ultrasound Cutoff Values for Severity Grading of Carpal Tunnel Syndrome?

PURPOSE: A growing body of evidence supports ultrasound (US) as an alternative first-line confirmatory test for carpal tunnel syndrome (CTS). Recent studies have demonstrated a correlation of US cross-sectional area with electrodiagnostic (EDX)-determined severity; however, it is unclear whether patient sex affects the cutoff values used for determining severity. The purpose of this study was to determine if patient sex affects US graded severity when using EDX as the reference standard. METHODS: A cohort of 367 women and 46 men, aged 18-90 years, from 1 orthopedic hand surgeon's practice underwent EDX and US. Distal motor latency and distal sensory latency of the median nerve were recorded. Severity was classified using a modified Bland severity scale. The US measurements of the cross-sectional area of the median nerve at the wrist crease were acquired by a fellowship-trained hand surgeon. Separate receiver operator characteristic curve analyses of the male and female groups were performed for US cutoff values. RESULTS: The cutoff value in both the female (F) and male (M) patients was 11 mm2 for mild (area under the curve = 0.76 F; 0.78 M), 12 mm2 for moderate (area under the curve = 0.75 F; 0.73 M), and 13 mm2 for severe (area under the curve = 0.75 F; 0.71 M) CTS. The sensitivity of the cutoffs for mild, moderate, and severe CTS in the female and male groups was 49% and 56%, 44% and 50%, and 49% and 44%, respectively. The specificity of the cutoffs for mild, moderate, and severe CTS in the female and male groups was 75% and 79%, 74% and 82%, and 83% and 78%, respectively. CONCLUSIONS: Patient sex does not appear to have a significant impact on the determination of CTS severity graded using US cutoff values. Ultrasound can be used to grade the severity of CTS with a 75% to 85% specificity but low sensitivity. A cutoff value of 13 mm2 can be used to classify CTS as severe. TYPE OF STUDY/LEVEL OF EVIDENCE: Prognostic II.

Safety and Efficacy of Balloon Kyphoplasty for Vertebral Fractures With Posterior Wall Disruption.

BACKGROUND: Percutaneous balloon kyphoplasty (BK) is widely accepted as both a safe and effective method for the treatment of symptomatic benign vertebral compression fractures (VCFs) of the thoracic and lumbar spines. A disruption in the posterior wall of the affected vertebra is often considered to be a relative or an absolute contraindication to BK. This study was performed to determine the safety as well as the efficacy of BK for vertebral body compression fractures associated with posterior wall disruption. METHODS: This was a retrospective, nonrandomized clinical cohort investigation of patients with VCF and posterior wall disruption treated with BK between 2010 and 2018. All cases were performed using a bipedicular technique. Each case was examined for cement leakage, anterior vertebral body height restoration, improvement in pain (determined by VAS) from baseline and 6-week postprocedure, and clinical sequelae from cement leakage. RESULTS: Ninety-eight consecutive patients with 157 VCF levels who underwent BK were evaluated. There was a significant improvement in anterior vertebral height, vertebral wedge angle, and local kyphotic angle in all cases. The mean preoperative VAS improved from 8.7 preprocedure to 2.5 postprocedure (P = .001). There were 14 (9%) cases with asymptomatic cement leakage outside of the vertebral body, and no patients experienced postprocedure neurological symptoms at the 6-week follow up. CONCLUSIONS: BK in the setting of posterior wall disruption was found to be a safe and highly effective treatment for patients with benign compression fractures. Posterior wall disruption should not be considered an absolute contraindication to BK.

The utility of routine head CT for hemorrhage surveillance in post-craniotomy patients undergoing anticoagulation for venous thromboembolism.

Anticoagulation for postoperative venous thromboembolism (VTE) may infer a higher risk of intracranial hemorrhage. We treat patients with VTE using slowly titrating intravenous heparin drip without bolus. When PTT is greater than 60 s, a head CT is obtained to monitor for the development of a intracranial hemorrhage before transition to oral anticoagulation. We evaluated the utility of routine surveillance head CT to monitor for intracranial hemorrhage during anticoagulation. This is a case series of neurosurgical patients in an academic quaternary hospital who developed a VTE after cranial procedures between 2007 and 2017. Over 11,000 patients were screened for the study. Patients' demographics data, surgical indication, PTT at the time of surveillance CT head, surveillance CT head findings, and patient's clinical course were reviewed. A total of 83 patients were included. Three patients (3.6%) developed a new subclinical hemorrhage on CT head imaging while on heparin drip. Interval CT head showed stable hemorrhage in all patients. Heparin drip was stopped in two patients and they both progressed from DVT to pulmonary embolism: one patient died due to cardiac arrest, the other patient was transitioned to oral anticoagulation. In the third patient heparin drip was continued uneventfully and transitioned to oral anticoagulation with no further clinical sequalae. Surveillance CT while on heparin drip for VTE management detected subclinical intracranial hemorrhage in a small subset of patients. Patients whose anticoagulation was stopped had progression of VTE. Undertreatment of VTE in the presence of subclinical hemorrhage may lead to significant morbidity and mortality.

Neurosurgical and neuro-immunological management of IgG4-related hypertrophic sclerosing pachymeningitis. A literature survey and discussion of a unique index case.

BACKGROUND: Dural thickening is observed in lymphoma, dural carcinomatosis, meningioma, tuberculosis, and autoimmune diseases. We encountered a patient with dural thickening and complaints of neck and back pain, numbness and loss of strength in the hands. The patient also suffered from polychondritis and had previously received steroid and methotrexate treatment for this indication. The patients' serum was also positive for ANA, yet she did not have any other findings suggesting lupus. Our radiological and pathological analysis revealed IHSP (IgG4-related hypertrophic sclerosing pachymeningitis). In this review study, we provided a detailed literature survey to increase the awareness about IHSP in the neurosurgical community. METHODS: MRI (magnetic resonance imaging)-based radiological analyses revealed a posterior extramedullary spinal mass extending from C2 to T2-T3 level. The dural mass was surgically excised and a broad panel of immunohistochemical markers including S100, EMA, CD246/ALK-1, CD45, CD20, CD79a, CD138, CD68, CD1a and CD34 was studied. Immunoglobulin heavy chain/kappa chain gene rearrangement analysis was performed which ruled out a lymphoproliferative disorder. RESULTS: MRI and pathological findings suggested IHSP. As the disease relapsed with a new anterior extramedullary multilobulated lesion extending from C5 to T1 level, the patient is now closely monitored for further medical and surgical treatment. CONCLUSIONS: IHSP is a relatively novel entity of hypertrophic pachymeningitis and should be included in the differential diagnosis of dural thickening. The fibrosis accompanying IHSP may not respond to medical treatment, which includes steroids and immunosuppressive agents. Additionally, neurological deficits, seizures, spinal decompression, hydrocephalus, or brainstem compression necessitate early surgical intervention. A continued vigilance is also necessary as the disease may relapse long-term following surgical treatment.

PPARδ and its ligand erucic acid may act anti-tumoral, neuroprotective, and myelin protective in neuroblastoma, glioblastoma, and Parkinson's disease.

In this review study, we focus on potential benefits of the transcription factor PPARδ and its ligand erucic acid (EA) in management of neuroectodermal tumors and Parkinson's Disease. PPARδ is a nuclear receptor and transcription factor that induces myelination, promotes oligodendroglial and neuronal differentiation, and possess anti-neuroinflammatory properties. While both pro-tumorigenic and anti-tumorigenic effects have been described for PPARδ, we propose that PPARδ may perform a predominantly anticancer role in tumors originating from the neuroectoderm. PPARδ ligand-activation via oleic acid and GW501516, or overexpression of PPARδ, elicits profound antitumor actions in neuroblastoma and melanoma. In glioblastomas, there is evidence indicating a differentiation failure of O2A (oligodendroglial-astrocytic biprogenitor) cells and it has been shown that EA reduced DNA synthesis in C6 rat glioblastoma spheroid cultures in clinically achievable concentrations. EA is a ω9 fatty acid which is being used in the treatment of adrenoleukodystrophy. EA is widely consumed in Asian countries via ingestion of cruciferous vegetables including mustard and rapeseed oil. EA also exerts antioxidant and anti-inflammatory activities. Recent studies of Parkinson's Disease (PD) have implicated demyelination, white matter pathology, oligodendroglial injury, and neural inflammation in the underlying pathophysiology. In the rotenone PD model in rats, PPARδ ligand GW501516 saves dopaminergic neurons during injury induced by chemical toxins and improves behavioral functioning in PD via alleviation of endoplasmic reticulum stress. PPARδ agonists also reduce the NLRP3 inflammasome-associated neural inflammation in the MPTP PD model in mice. Herein, we propose that PPARδ and its ligand EA highly deserve to be studied in animal models of neuroblastoma, glioblastoma, and PD.

Relationship Between Preoperative Opioid Use and Postoperative Pain in Patients Undergoing Minimally Invasive Stand-Alone Lateral Lumbar Interbody Fusion.

BACKGROUND: Opioid use in the management of pain secondary to spinal disorders has grown significantly in the United States. However, preoperative opioid use may complicate recovery in patients undergoing surgical procedures. OBJECTIVE: To test our hypothesis that prolonged preoperative opioid use may lead to poorer patient outcomes following minimally invasive stand-alone lateral lumbar interbody fusion (LLIF) for lumbar degenerative disc disease. METHODS: A consecutive series of patients from a single institution undergoing LLIF between December 2009 and January 2017 was retrospectively analyzed. Patients were categorized according to the presence or absence of prescribed preoperative opioid use for at least 3 mo. Outcomes included the Oswestry Disability Index (ODI), visual analog scale (VAS), and Short Form 36 Physical and Mental Summary Scores (SF-36 PCS, SF-36 MCS). RESULTS: Of 107 patients, 57 (53.1%) were prescribed preoperative opioids. There was no significant difference in preoperative ODI, VAS score, SF-36 PCS, or SF-36 MCS between opioid use groups. Mean postoperative ODI was greater in patients with preoperative opioid use at 41.7 ± 16.9 vs 22.2 ± 16.0 (P = .002). Mean postoperative VAS score was greater in patients prescribed preoperative opioids, while magnitude of decrease in VAS score was greater in opioid-naïve patients (P = .001). Postoperative SF-36 PCS was 33.1 ± 10.6 in the opioid use group compared to 43.7 ± 13.1 in the nonuse group (P = .001). CONCLUSION: Following LLIF, patients prescribed preoperative opioids had increased postoperative lumbar pain, disability, and subjective pain.

Hypothesis: Could Hepatitis B vaccine act as an immune adjuvant in glioblastoma? Clues to conduct further epidemiological analyses.

A failure of neurodevelopmental differentiation at the level of oligodendroglial-astrocytic biprogenitors (O2A) is shown to be involved in the pathogenesis of both multiple sclerosis (MS) and glioblastoma multiforme (GBM). In this review article, we suggest that certain antigens of Hepatitis B Virus (HBV) and HBV-Vaccine (HBV-V) could act as immune stimulants in GBM treatment based on several lines of evidence. HBV-Vs may cause rare but prominent neuroimmune side effects including demyelination and multiple sclerosis, which may be associated with HBV-proteins creating antigenic mimicry of oligodendroglial progenitors. The combined prevalance of HBV and Hepatitis C Virus-carrier state is less in patients with brain tumors compared to healthy subjects. Furthermore, within the population of patients with brain tumors, the prevalence is even about two times lesser in GBM in comparison to those with a diagnosis of meningioma. Although indirectly, this epidemiological data may indicate that the immune response triggered against hepadnavirus antigens would eliminate aberrantly differentiating O2A progenitor cells giving rise to GBMs. Moreover, Hepatitis B surface antigen-antibody variable domain is among the top 100 differentially expressed transcripts in fresh frozen and formalin-fixed paraffin-embeded specimens obtained from pediatric GBM tissues in comparison to the control brain tissues. However, the provided evidence is still premature and we think that HBV-V warrants investigation first by epidemiological studies and then by animal experiments to determine whether it reduces the risk of GBM and whether it could slow GBM growth via immune stimulation.

Erucic acid, a nutritional PPARδ-ligand may influence Huntington's disease pathogenesis.

Increasing recent evidence suggests a key role of oligodendroglial injury and demyelination in the pathophysiology of Huntington's Disease (HD) and the transcription factor PPARδ is critical for oligodendroglial regeneration and myelination. PPARδ directly involves in the pathogenesis of HD and treatment with a brain-permeable PPARδ-agonist (KD3010) alleviates its severity in mice. Erucic acid (EA) is also a PPARδ-ligand ω9 fatty acid which is highly consumed in Asian countries through ingesting cruciferous vegetables such as rapeseed (Brassica napus) and indian mustard (Brassica juncea). EA is also an ingredient of Lorenzo's oil employed in the medical treatment of adrenoleukodystrophy and can be converted to nervonic acid, a component of myelin. HD pathogenesis also involves oxidative and inflammatory injury and EA exerts antioxidative and antiinflammatory efficacies including inhibition of thrombin and elastase. Consumption of rapeseed, indian mustard, and Canola oils (containing EA) improves cognitive parameters in animal models, as well as treatment with pure EA. Moreover, erucamide, an endogenous EA-amide derivative regulating angiogenesis and water balance, exerts antidepressive and anxiolytic effects in mice. Hitherto, no study has investigated the therapeutic potential of EA in HD and we believe that it strongly merits to be studied in animal models of HD as a potential therapeutic.

Noscapine, a Non-addictive Opioid and Microtubule-Inhibitor in Potential Treatment of Glioblastoma.

Noscapine is a phthalide isoquinoline alkaloid that easily traverses the blood brain barrier and has been used for years as an antitussive agent with high safety. Despite binding opioid receptors, noscapine lacks significant hypnotic and euphoric effects rendering it safe in terms of addictive potential. In 1954, Hans Lettré first described noscapine as a mitotic poison. The drug was later tested for cancer treatment in the early 1960's, yet no effect was observed likely as a result of its short biological half-life and limited water solubility. Since 1998, it has regained interest thanks to studies from Emory University, which showed its anticancer activity in animal models with negligible toxicity. In contrast to other microtubule-inhibitors, noscapine does not affect the total intracellular tubulin polymer mass. Instead, it forces the microtubules to spend an increased amount of time in a paused state leading to arrest in mitosis and subsequently inducing mitotic slippage/mitotic catastrophe/apoptosis. In experimental models, noscapine does not induce peripheral neuropathy, which is common with other microtubule inhibitors. Noscapine also inhibits tumor growth and enhances cancer chemosensitivity via selective blockage of NF-κB, an important transcription factor in glioblastoma pathogenesis. Due to their anticancer activities and high penetration through the blood-brain barrier, noscapine analogues strongly deserve further study in various animal models of glioblastoma as potential candidates for future patient therapy.