A proposed stratification system to address the heterogeneity of Subdural Hematoma Outcome reporting in the literature.

A major challenge within the academic literature on SDHs has been inconsistent outcomes reported across studies. Historically, patients have been categorized by the blood-product age identified on imaging (i.e., acute, subacute, or chronic). However, this schematic has likely played a central role in producing the heterogeneity encountered in the literature. In this investigation, a total of 494 patients that underwent SDH evacuation at a tertiary medical center between November 2013-December 2021 were retrospectively identified. Mechanism of injury was reviewed by the authors and categorized as either positive or negative for a high-velocity impact (HVI) injury. Any head strike injury leading to the formation of a SDH while traveling at a velocity beyond that of normal locomotion or daily activities was categorized as an HVI. Patients were subsequently stratified by those with an acute SDHs after a high-velocity impact (aSDHHVI), those with an acute SDH without a high-velocity impact injury (aSDHWO), and those with any combination of subacute or chronic blood products (mixed-SDH [mSDH]). Nine percent (n = 44) of patients experienced an aSDHHVI, 23% (n = 113) aSDHWO, and 68% (n = 337) mSDH. Between these groups, highly distinct patient populations were identified using several metrics for comparison. Most notably, aSDHHVI had a significantly worse neurological status at discharge (50% vs. 23% aSDHWO vs. 8% mSDH; p < 0.001) and mortality (25% vs. 8% aSDHWO vs. 4% mSDH; p < 0.001). Controlling for gender, midline shift (mm), and anticoagulation use in the acute SDH population, multivariable logistic regression revealed a 6.85x odds ratio (p < 0.001) for poor outcomes in those with a positive history for a high-velocity impact injury. As such, the distribution of patients that suffer an HVI related acute SDH versus those that do not can significantly affect the outcomes reported. Adoption of this stratification system will help address the heterogeneity of SDH reporting in the literature while still closely aligning with conventional reporting.

Observation of slow light in glide-symmetric photonic-crystal waveguides.

We report optical transmission measurements on suspended silicon photonic-crystal waveguides, where one side of the photonic lattice is shifted by half a period along the waveguide axis. The combination of this glide symmetry and slow light leads to a strongly enhanced chiral light-matter interaction but the interplay between slow light and backscattering has not been investigated experimentally in such waveguides. We build photonic-crystal resonators consisting of glide-symmetric waveguides terminated by reflectors and use transmission measurements as well as evanescent coupling to map out the dispersion relation. We find excellent agreement with theory and measure group indices exceeding 90, implying significant potential for applications in slow-light devices and chiral quantum optics. By measuring resonators of different length, we assess the role of backscattering induced by fabrication imperfections and its intimate connection to the group index.

Biogenically proficient synthesis and characterization of silver nanoparticles employing marine procured fungi Aspergillus brunneoviolaceus along with their antibacterial and antioxidative potency.

OBJECTIVES: To assess the extracellular synthesis of silver nanoparticles using marine derived fungi Aspergillus brunneoviolaceus with their antibacterial and antioxidant activities. RESULTS: The biosynthesis of silver nanoparticles was estimated by the change in color from light yellow to dark brown within 36 h as the reaction progressed. UV-Visible spectroscopy exhibited its stability at 411 nm; ATR-FTIR spectroscopy depicted the functional group responsible for its production; X-Ray Diffraction denoted its crystalline FCC structure resembling the peaks in XRD pattern, corresponding to [111], [200], [220], [311] and [222] planes; TEM imaging revealed its spherical morphology with the particle size ranging from 0.72 to 15.21 nm and Tauc's plot analysis that disclosed its band gap energy as 2.44 eV that manifested the potential of AgNPs to be semiconductors. The characterization data henceforth, confirmed the efficient production of silver nanoparticles. The biosynthesized AgNPs expressed strong antibacterial activity against two Gram-positive and three Gram-negative bacteria. They also proved to possess higher antioxidative potentials by showing their potent radical scavenging activity against DPPH (2, 2-diphenyl-1-picrylhydrazyl). CONCLUSIONS: The study unfolds the prospect for further utilization of this mycogenically synthesized AgNPs as antibacterial, antioxidative and anticancer agents.

Early versus delayed postoperative radiotherapy for treatment of low-grade gliomas.

BACKGROUND: This is an update of the review originally published in 2011 and first updated in 2015. In most people with low-grade gliomas (LGG), the primary treatment regimen remains a combination of surgery followed by postoperative radiotherapy. However, the optimal timing of radiotherapy is controversial. It is unclear whether to use radiotherapy in the early postoperative period, or whether radiotherapy should be delayed until tumour progression occurs. OBJECTIVES: To assess the effects of early postoperative radiotherapy versus radiotherapy delayed until tumour progression for low-grade intracranial gliomas in people who had initial biopsy or surgical resection. SEARCH METHODS: Original searches were run up to September 2014. An updated literature search from September 2014 through November 2019 was performed on the following electronic databases: the Cochrane Central Register of Controlled Trials (CENTRAL; 2019, Issue 11), MEDLINE via Ovid (September 2014 to November week 2 2019), and Embase via Ovid (September 2014 to 2019 week 46) to identify trials for inclusion in this Cochrane review update. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that compared early versus delayed radiotherapy following biopsy or surgical resection for the treatment of people with newly diagnosed intracranial LGG (astrocytoma, oligodendroglioma, mixed oligoastrocytoma, astroblastoma, xanthoastrocytoma, or ganglioglioma). Radiotherapy may include conformal external beam radiotherapy (EBRT) with linear accelerator or cobalt-60 sources, intensity-modulated radiotherapy (IMRT), or stereotactic radiosurgery (SRS). DATA COLLECTION AND ANALYSIS: Three review authors independently assessed the trials for inclusion and risk of bias, and extracted study data. We resolved any differences between review authors by discussion. Adverse effects were also extracted from the study report. We performed meta-analyses using a random-effects model with inverse variance weighting. MAIN RESULTS: We included one large, multi-institutional, prospective RCT, involving 311 participants; the risk of bias in this study was unclear. This study found that early postoperative radiotherapy was associated with an increase in time to progression compared to observation (and delayed radiotherapy upon disease progression) for people with LGG but did not significantly improve overall survival (OS). The median progression-free survival (PFS) was 5.3 years in the early radiotherapy group and 3.4 years in the delayed radiotherapy group (hazard ratio (HR) 0.59, 95% confidence interval (CI) 0.45 to 0.77; P < 0.0001; 311 participants; 1 trial; low-quality evidence). The median OS in the early radiotherapy group was 7.4 years, while the delayed radiotherapy group experienced a median overall survival of 7.2 years (HR 0.97, 95% CI 0.71 to 1.33; P = 0.872; 311 participants; 1 trial; low-quality evidence). The total dose of radiotherapy given was 54 Gy; five fractions of 1.8 Gy per week were given for six weeks. Adverse effects following radiotherapy consisted of skin reactions, otitis media, mild headache, nausea, and vomiting. Rescue therapy was provided to 65% of the participants randomised to delayed radiotherapy. People in both cohorts who were free from tumour progression showed no differences in cognitive deficit, focal deficit, performance status, and headache after one year. However, participants randomised to the early radiotherapy group experienced significantly fewer seizures than participants in the delayed postoperative radiotherapy group at one year (25% versus 41%, P = 0.0329, respectively). AUTHORS' CONCLUSIONS: Given the high risk of bias in the included study, the results of this analysis must be interpreted with caution. Early radiation therapy was associated with the following adverse effects: skin reactions, otitis media, mild headache, nausea, and vomiting. People with LGG who underwent early radiotherapy showed an increase in time to progression compared with people who were observed and had radiotherapy at the time of progression. There was no significant difference in overall survival between people who had early versus delayed radiotherapy; however, this finding may be due to the effectiveness of rescue therapy with radiation in the control arm. People who underwent early radiation had better seizure control at one year than people who underwent delayed radiation. There were no cases of radiation-induced malignant transformation of LGG. However, it remained unclear whether there were differences in memory, executive function, cognitive function, or quality of life between the two groups since these measures were not evaluated.

Whole brain radiation therapy (WBRT) alone versus WBRT and radiosurgery for the treatment of brain metastases.

BACKGROUND: Historically, whole brain radiation therapy (WBRT) has been the main treatment for brain metastases. Stereotactic radiosurgery (SRS) delivers high-dose focused radiation and is being increasingly utilized to treat brain metastases. The benefit of adding SRS to WBRT is unclear. This is an updated version of the original Cochrane Review published in Issue 9, 2012. OBJECTIVES: To assess the efficacy of WBRT plus SRS versus WBRT alone in the treatment of adults with brain metastases. SEARCH METHODS: For the original review, in 2009 we searched the following electronic databases: CENTRAL, MEDLINE, Embase, and CancerLit in order to identify trials for inclusion in this review. For the first update the searches were updated in May 2012.For this update, in May 2017 we searched CENTRAL, MEDLINE, and Embase in order to identify trials for inclusion in the review. SELECTION CRITERIA: We restricted the review to randomized controlled trials (RCTs) that compared use of WBRT plus SRS versus WBRT alone for upfront treatment of adults with newly diagnosed metastases (single or multiple) in the brain resulting from any primary, extracranial cancer. DATA COLLECTION AND ANALYSIS: We used the generic inverse variance method, random-effects model in Review Manager 5 for the meta-analysis. MAIN RESULTS: We identified three studies and one abstract for inclusion but we could only include two studies, with a total of 358 participants in a meta-analysis. This found no difference in overall survival (OS) between the WBRT plus SRS and WBRT alone groups (hazard ratio (HR) 0.82, 95% confidence interval (CI) 0.65 to 1.02; 2 studies, 358 participants; moderate-quality evidence). For participants with one brain metastasis median survival was significantly longer in the WBRT plus SRS group (6.5 months) versus WBRT group (4.9 months; P = 0.04). Participants in the WBRT plus SRS group had decreased local failure compared to participants who received WBRT alone (HR 0.27, 95% CI 0.14 to 0.52; 2 studies, 129 participants; moderate-quality evidence). Furthermore, we observed an improvement in performance status scores and decrease in steroid use in the WBRT plus SRS group (risk ratio (RR) 0.64 CI 0.42 to 0.97; 1 study, 118 participants; low-quality evidence). Unchanged or improved Karnofsky Performance Scale (KPS) at six months was seen in 43% of participants in the combined therapy group versus only 28% in the WBRT-alone group (RR 0.78 CI 0.61 to 1.00; P value = 0.05; 1 study, 118 participants; low-quality evidence). Overall, risk of bias in the included studies was unclear. AUTHORS' CONCLUSIONS: Since the last version of this review we have identified one new study that met the inclusion criteria. However, due to a lack of data from this study we were not able to include it in a meta-analysis. Given the unclear risk of bias in the included studies, the results of this analysis have to be interpreted with caution. In our analysis of all included participants, SRS plus WBRT did not show a survival benefit over WBRT alone. However, performance status and local control were significantly better in the SRS plus WBRT group. Furthermore, significantly longer OS was reported in the combined treatment group for recursive partitioning analysis (RPA) Class I patients as well as patients with single metastasis. Most of our outcomes of interest were graded as moderate-quality evidence according to the GRADE criteria and the risk of bias in the majority of included studies was mostly unclear.

Biopsy versus resection for the management of low-grade gliomas.

BACKGROUND: This is an updated version of the original Cochrane review published in 2013, Issue 4.Low-grade gliomas (LGG) constitute a class of slow-growing primary brain neoplasms. Patients with clinically and radiographically suspected LGG have two initial surgical options, biopsy or resection. Biopsy can provide a histological diagnosis with minimal risk but does not offer a direct treatment. Resection may have additional benefits such as increasing survival and delaying recurrence, but is associated with a higher risk for surgical morbidity. There remains controversy about the role of biopsy versus resection and the relative clinical outcomes for the management of LGG. OBJECTIVES: To assess the clinical effectiveness of biopsy compared to surgical resection in patients with a new lesion suspected to be a LGG. SEARCH METHODS: The following electronic databases were searched in 2012 for the first version of the review: Cochrane Central Register of Controlled Trials (CENTRAL) (2012, Issue 11), MEDLINE (1950 to November week 3 2012), Embase (1980 to Week 46 2012). For this updated version, the following electronic databases were searched: Cochrane Central Register of Controlled Trials (CENTRAL) (2016, Issue 5), MEDLINE (Nov 2012 to June week 3 2016), Embase (Nov 2012 to 2016 week 26). All relevant articles were identified on PubMed and by using the 'related articles' feature. We also searched unpublished and grey literature including ISRCTN-metaRegister of Controled Trials, Physicians Data Query and ClinicalTrials.gov for ongoing trials. SELECTION CRITERIA: We planned to include patients of any age with a suspected intracranial LGG receiving biopsy or resection within a randomized clinical trial (RCT) or controlled clinical trial (CCT). Patients with prior resections, radiation therapy, or chemotherapy for LGG were excluded. Outcome measures included overall survival (OS), progression-free survival (PFS), functionally independent survival (FIS), adverse events, symptom control, and quality of life (QoL). DATA COLLECTION AND ANALYSIS: A total of 1375 updated citations were searched and critically analyzed for relevance. This was undertaken independently by two review authors. The original electronic database searches yielded a total of 2764 citations. In total, 4139 citations have been critically analyzed for this updated review. MAIN RESULTS: No new RCTs of biopsy or resection for LGG were identified. No additional ineligible non-randomized studies (NRS) were included in this updated review. Twenty other ineligible studies were previously retrieved for further analysis despite not meeting the pre-specified criteria. Ten studies were retrospective or were literature reviews. Three studies were prospective, however they were limited to tumor recurrence and volumetric analysis and extent of resection. One study was a population-based parallel cohort in Norway, but not an RCT. Four studies were RCTs, however patients were randomized with respect to varying radiotherapy regimens to assess timing and dose of radiation. One RCT was on high-grade gliomas (HGGs) and not LGG. Finally, one RCT evaluated diffusion tensor imaging (DTI)-based neuro-navigation for surgical resection. AUTHORS' CONCLUSIONS: Since the last version of this review, no new studies have been identified for inclusion and currently there are no RCTs or CCTs available on which to base definitive clinical decisions. Therefore, physicians must approach each case individually and weigh the risks and benefits of each intervention until further evidence is available. Some retrospective studies and non-randomized prospective studies do seem to suggest improved OS and seizure control correlating to higher extent of resection. Future research could focus on RCTs to determine outcomes benefits for biopsy versus resection.

Early versus delayed postoperative radiotherapy for treatment of low-grade gliomas.

BACKGROUND: In most people with low-grade gliomas (LGG), the primary treatment regimen remains a combination of surgery followed by postoperative radiotherapy. However, the optimal timing of radiotherapy is controversial. It is unclear whether to use radiotherapy in the early postoperative period, or whether radiotherapy should be delayed until tumour progression occurs. OBJECTIVES: To assess the effects of early postoperative radiotherapy versus radiotherapy delayed until tumour progression for low-grade intracranial gliomas in people who had initial biopsy or surgical resection. SEARCH METHODS: We searched up to September 2014 the following electronic databases: the Cochrane Register of Controlled Trials (CENTRAL, Issue 8, 2014), MEDLINE (1948 to Aug week 3, 2014), and EMBASE (1980 to Aug week 3, 2014) to identify trials for inclusion in this Cochrane review. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that compared early versus delayed radiotherapy following biopsy or surgical resection for the treatment of people with newly diagnosed intracranial LGG (astrocytoma, oligodendroglioma, mixed oligoastrocytoma, astroblastoma, xanthoastrocytoma, or ganglioglioma). Radiotherapy may include conformal external beam radiotherapy (EBRT) with linear accelerator or cobalt-60 sources, intensity-modulated radiotherapy (IMRT), or stereotactic radiosurgery (SRS). DATA COLLECTION AND ANALYSIS: Three review authors independently assessed the trials for inclusion and risk of bias, and extracted study data. We resolved any differences between review authors by discussion. Adverse effects were also extracted from the study report. We performed meta-analyses using a random-effects model with inverse variance weighting. MAIN RESULTS: We included one large, multi-institutional, prospective RCT, involving 311 participants; the risk of bias in this study was unclear. This study found that early postoperative radiotherapy is associated with an increase in time to progression compared to observation (and delayed radiotherapy upon disease progression) for people with LGG but does not significantly improve overall survival (OS). The median progression-free survival (PFS) was 5.3 years in the early radiotherapy group and 3.4 years in the delayed radiotherapy group (hazard ratio (HR) 0.59, 95% confidence interval (CI) 0.45 to 0.77; P value < 0.0001; 311 participants; 1 trail; low quality evidence). The median OS in the early radiotherapy group was 7.4 years, while the delayed radiotherapy group experienced a median overall survival of 7.2 years (HR 0.97, 95% CI 0.71 to 1.33; P value = 0.872; 311 participants; 1 trail; low quality evidence). The total dose of radiotherapy given was 54 Gy; five fractions of 1.8 Gy per week were given for six weeks. Adverse effects following radiotherapy consisted of skin reactions, otitis media, mild headache, nausea, and vomiting. Rescue therapy was provided to 65% of the participants randomised to delayed radiotherapy. People in both cohorts who were free from tumour progression showed no differences in cognitive deficit, focal deficit, performance status, and headache after one year. However, participants randomised to the early radiotherapy group experienced significantly fewer seizures than participants in the delayed postoperative radiotherapy group at one year (25% versus 41%, P value = 0.0329, respectively). AUTHORS' CONCLUSIONS: Given the high risk of bias in the included study, the results of this analysis must be interpreted with caution. Early radiation therapy was associated with the following adverse effects: skin reactions, otitis media, mild headache, nausea, and vomiting. People with LGG who undergo early radiotherapy showed an increase in time to progression compared with people who were observed and had radiotherapy at the time of progression. There was no significant difference in overall survival between people who had early versus delayed radiotherapy; however, this finding may be due to the effectiveness of rescue therapy with radiation in the control arm. People who underwent early radiation had better seizure control at one year than people who underwent delayed radiation. There were no cases of radiation-induced malignant transformation of LGG. However, it remains unclear whether there are differences in memory, executive function, cognitive function, or quality of life between the two groups since these measures were not evaluated.

Extreme-aged patients (≥ 85 years) experience similar outcomes as younger geriatric patients following chronic subdural hematoma evacuation: a matched cohort study.

Subdural hematoma (SDH) evacuation represents one of the most frequently performed neurosurgical procedures. Several reports cite a rise in both the age and number of patient's requiring treatment, due in part to an aging population and expanded anticoagulation use. However, limited data and conflicting conclusions exist on extreme-aged geriatric patients (≥ 85 years of age) after undergoing surgery. Patients undergoing SDH evacuation at a tertiary academic medical center between November 2013-December 2021 were retrospectively identified. The study group consisted of patients ≥ 85 years (Group 1) diagnosed with a chronic SDH surgically evacuated. A control group was created matching patients by 70-84 years of age, gender, and anticoagulation use (Group 2). Multiple metrics were evaluated between the two including length-of hospital-stay, tracheostomy/PEG placement, reoperation rate, complications, discharge location, neurological outcome at the time of discharge, and survival. A total of 130 patients were included; 65 in Group 1 and 65 in Group 2. Patient demographics, medical comorbidities, SDH characteristics, international normalized ratio, partial thromboplastin time, and use of blood thinning agents were similar between the two groups. Kaplan Meier survival analysis at one-year was 80% for Group 1 and 76% for Group 2. No significant difference was identified using the log-rank test for equality of survivor functions (p = 0.26). All measured outcomes including GCS at time of discharge, length of stay, rate of reoperations, and neurological outcome were statistically similar between the two groups. Backwards stepwise conditional logistic regression revealed no significant association between poor outcomes at the time of discharge and age. Alternatively, anticoagulation use was found to be associated with poor outcomes (OR 3.55, 95% CI 1.08-11.60; p = 0.036). Several outcome metrics and statistical analyses were used to compare patients ≥ 85 years of age to younger geriatric patients (70-84 years) in a matched cohort study. Adjusting for age group, gender, and anticoagulation use, no significant difference was found between the two groups including neurological outcome at discharge, reoperation rate, and survival.

Phase I trial of a multi-epitope-pulsed dendritic cell vaccine for patients with newly diagnosed glioblastoma.

BACKGROUND: This study evaluated the safety and immune responses to an autologous dendritic cell vaccine pulsed with class I peptides from tumor-associated antigens (TAA) expressed on gliomas and overexpressed in their cancer stem cell population (ICT-107). METHODS: TAA epitopes included HER2, TRP-2, gp100, MAGE-1, IL13Rα2, and AIM-2. HLA-A1- and/or HLA-A2-positive patients with glioblastoma (GBM) were eligible. Mononuclear cells from leukapheresis were differentiated into dendritic cells, pulsed with TAA peptides, and administered intradermally three times at two-week intervals. RESULTS: Twenty-one patients were enrolled with 17 newly diagnosed (ND-GBM) and three recurrent GBM patients and one brainstem glioma. Immune response data on 15 newly diagnosed patients showed 33 % responders. TAA expression by qRT-PCR from fresh-frozen tumor samples showed all patient tumors expressed at least three TAA, with 75 % expressing all six. Correlations of increased PFS and OS with quantitative expression of MAGE1 and AIM-2 were observed, and a trend for longer survival was observed with gp100 and HER2 antigens. Target antigens gp100, HER1, and IL13Rα2 were downregulated in recurrent tumors from 4 HLA-A2+ patients. A decrease in or absence of CD133 expression was seen in five patients who underwent a second resection. At a median follow-up of 40.1 months, six of 16 ND-GBM patients showed no evidence of tumor recurrence. Median PFS in newly diagnosed patients was 16.9 months, and median OS was 38.4 months. CONCLUSIONS: Expression of four ICT-107 targeted antigens in the pre-vaccine tumors correlated with prolonged overall survival and PFS in ND-GBM patients. The goal of targeting tumor antigens highly expressed on glioblastoma cancer stem cells is supported by the observation of decreased or absent CD133 expression in the recurrent areas of gadolinium-enhanced tumors.

Biopsy versus resection for the management of low-grade gliomas.

BACKGROUND: Low-grade gliomas (LGG) constitute a class of slow-growing primary brain neoplasms. Patients with clinically and radiographically suspected LGG have two initial surgical options, biopsy or resection. Biopsy can provide a histological diagnosis with minimal risk but does not offer a direct treatment. Resection may have additional benefits such as increasing survival and delaying recurrence, but is associated with a higher risk for surgical morbidity. There remains controversy about the role of biopsy versus resection and the relative clinical outcomes for the management of LGG. OBJECTIVES: To assess the clinical effectiveness of biopsy compared to surgical resection in patients with a new lesion suspected to be a LGG. SEARCH METHODS: The following electronic databases were searched: Cochrane Central Register of Controlled Trials (CENTRAL) (2012, Issue 11), MEDLINE (1950 to week 3 November 2012), EMBASE (1980 to Week 46 2012). Unpublished and grey literature including Metaregister, Physicians Data Query, www.controlled-trials.com/rct, www.clinicaltrials.gov, and www.cancer.gov/clinicaltrials were also queried for ongoing trials. SELECTION CRITERIA: Patients of any age with a suspected intracranial LGG receiving biopsy or resection within a randomized clinical trial (RCT) or controlled clinical trial (CCT) were included. Patients with prior resections, radiation therapy, or chemotherapy for LGG were excluded. Outcome measures included overall survival (OS), progression free survival (PFS), functionally independent survival (FIS), adverse events, symptom control, and quality of life (QoL). DATA COLLECTION AND ANALYSIS: A total of 2764 citations were searched and critically analyzed for relevance. This effort was undertaken by three independent review authors. MAIN RESULTS: No RCTs of biopsy or resection for LGG were identified. Twenty other studies were retrieved for analysis based on pre-specified selection criteria. Ten studies were retrospective or literature reviews. Three studies were prospective but were limited to tumor recurrence or the extent of resection. One study was a population-based parallel cohort and not an RCT. Four studies were RCTs, however patients were randomized with respect to varying radiotherapy regimens to assess timing and dose of radiation. One RCT was focused on high-grade gliomas and not LGG. One last RCT evaluated diffusion tensor imaging (DTI)-based neuro-navigation for surgical resection. AUTHORS' CONCLUSIONS: Currently there are no randomized clinical trials or controlled clinical trials available on which to base clinical decisions. Therefore, physicians must approach each case individually and weigh the risks and benefits of each intervention until further evidence is available. Future research could focus on randomized clinical trials to determine outcomes benefits for biopsy versus resection.

Outcomes of percutaneous and paddle lead implantation for spinal cord stimulation: a comparative analysis of complications, reoperation rates, and health-care costs.

OBJECTIVES: Spinal cord stimulation (SCS) is a well-established modality for the treatment of chronic pain, and can utilize percutaneous or paddle leads. While percutaneous leads are less invasive, they have been shown to have higher lead migration rates. In this study, we compared the long-term outcomes and health-care costs associated with paddle and percutaneous lead implantation. MATERIALS AND METHODS: We utilized the MarketScan data base to examine patients who underwent percutaneous or paddle lead SCS system implantation from 2000 to 2009. Outcomes including complications, reoperation rates, and health-care costs were evaluated in propensity score matched cohorts using univariate and multivariate analyses. RESULTS: The study cohort was comprised of 13,774 patients. At 90 days following the initial procedure, patients in the SCS paddle group were more likely to develop a postoperative complication than patients receiving percutaneous systems (3.4% vs. 2.2%, p = 0.0005). Two-year (6.3% vs. 3.5%, p = 0.0056) and long-term (five+ years) (22.9% vs. 8.5%, p < 0.0008) reoperation rates were significantly higher in those with percutaneous lead systems. However, long-term health-care costs were similar for those receiving paddle and percutaneous leads ($169,768 vs. $186,139, p = 0.30). CONCLUSIONS: While the implantation of paddle leads is associated with slightly higher initial postoperative complications, these leads are associated with significantly lower long-term reoperation rates. Nonetheless, long-term health-care costs are similar between paddle and percutaneous leads. Additional improvements in SCS technologies that address the shortcomings of current systems are needed to reduce the risk of reoperation due to hardware failure. Further study is required to evaluate the efficacy of newer percutaneous and paddle SCS systems and examine their comparative outcomes.

Insurance disparities in the outcomes of spinal cord stimulation surgery.

OBJECTIVES: The Affordable Care Act aims to expand health insurance and to help narrow existing health care disparities. Medicaid patients have previously been noted to be at an increased risk for impaired access to health care, delayed medical treatment, and the receipt of substandard care. Conversely, those with commercial insurance may be subject to overtreatment. The goal of this study was to evaluate how Medicaid versus commercial insurance status affects outcomes following spinal cord stimulation (SCS) surgery. MATERIALS AND METHODS: A retrospective cohort study of 13,774 patients underwent either percutaneous or paddle permanent SCS implantation, selected from the Thomson Reuter's MarketScan database between 2000 and 2009. Patients were characterized by age at initial procedure, gender, baseline comorbidity burden, procedure-associated diagnosis code, follow-up, and type of insurance (Medicaid vs. commercial insurance). Outcome measures included probability of reoperation, timing and type of reoperation, presence of postoperative complications (immediate, 30 days, and 90 days), and overall utilization of health resources postoperatively. Multivariate analysis was performed comparing the relative effect of insurance status on outcomes following initial surgery. RESULTS: Medicaid patients had greater healthcare resource utilization as measured by medications prescribed, emergency department visits, and length of stay; however, commercially insured patients had significantly higher overall costs ($110,908 vs. $64,644, p < 0.0001). Commercial and Medicaid patients did not significantly differ in their complication rates during the index hospitalization or at 30 days or 90 days postoperatively. The group were also not significantly different in their two-year reoperation rates (7.32% vs. 5.06%, p = 0.0513). CONCLUSIONS: There are substantial insurance disparities that affect healthcare utilization and overall cost following SCS. Efforts for national healthcare reform should examine system factors that will reduce socioeconomic disparities in outcomes following SCS.

Long-term survival after salvage pemetrexed for refractory primary T-cell lymphoma of the CNS.

Primary T-cell CNS lymphoma is a rare and aggressive malignancy. High-dose methotrexate (MTX) based chemotherapy regimens are used as standard first-line treatment, followed by consolidative strategies to improve the duration of response. Although MTX-based therapy has been shown to be efficacious, treatment options for MTX-refractory disease are not well-defined. Here, we report a case of a 38-year-old man with refractory primary T-cell CNS lymphoma who demonstrated a complete response to pemetrexed treatment. He subsequently received conditioning chemotherapy consisting of thiotepa, busulfan and cyclophosphamide followed by autologous stem cell transplantation. The patient continues to remain recurrence-free to date at 9 years post-treatment.

Proton Therapy for Skull Base Chondrosarcoma.

Chondrosarcoma is a type of an endochondral bone malignancy that is primarily treated surgically with radiation therapy used in the adjuvant setting or in cases of unresectable disease. Proton therapy has potential advantages compared with traditional photon therapy for the treatment of tumors in close proximity to critical structures due to the theoretic lower exit dose. Studies have shown improved survival in patients with skull base chondrosarcoma who undergo proton therapy. However, there is a lack of randomized data. Further studies are needed to define the role of proton therapy in the treatment of skull base chondrosarcoma.

Racial and gender disparities and the role of primary tumor type on inpatient outcomes following craniotomy for brain metastases.

BACKGROUND: Race and gender disparities in outcomes have been documented in many cancers. Our study evaluated the role of race, gender, and tumor primary site in predicting in-hospital mortality, discharge disposition, and complications among patients with brain metastases. METHODS: Using Nationwide Inpatient Sample (NIS) data from 1998 to 2007, we evaluated in-patient outcomes of brain metastases patients who underwent a craniotomy in U.S. hospitals. Univariate and multivariate analyses were used to assess the effect of patient/tumor characteristics in predicting the proposed outcomes. RESULTS: NIS estimated 78,170 patients with metastatic brain tumors underwent craniotomy between 1998 and 2007 in the United States. Median age was 59.2 years, 52.1 % were women, and 6.4 % were black. In-hospital mortality rate was 2.2 % with an average length of stay of 7.6 days. Black patients had significantly higher morbidity and nonroutine discharges than whites/others (p < .0001). Black women had almost twice the mortality (3.4 vs 1.8 %, p < .0001), a higher complication rate (24.6 vs 18.8 %, p < .0001), longer hospital stays (10.0 vs 7.3 days, p < .0001), and more nonroutine discharges (45.1 vs 36.8 %, p < .0001), compared with white/other women. Tumor histology was a significant predictor of outcomes, with female lung cancer patients having the highest odds of mortality and primary gastrointestinal tumors having the highest number of complications. CONCLUSIONS: Evidence of race and gender disparities in outcomes were found in black patients, especially in black females who underwent surgical resection for brain metastases. These findings highlight an opportunity to reduce the gap of outcome disparities in brain metastasis patients.

Whole brain radiation therapy (WBRT) alone versus WBRT and radiosurgery for the treatment of brain metastases.

BACKGROUND: Historically, whole brain radiation therapy (WBRT) has been the main treatment for brain metastases. Stereotactic radiosurgery (SRS) delivers high-dose focused radiation and is being increasingly utilized to treat brain metastases. The benefit of adding SRS to WBRT is unclear. This is an updated version of the original Cochrane review published in Issue 6, 2010. OBJECTIVES: To assess the efficacy of WBRT plus SRS versus WBRT alone in the treatment of brain metastases. SEARCH METHODS: In the original review we searched the following electronic databases: Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 2, 2009), MEDLINE (1966 to 2009), EMBASE (1980 to 2009), and CancerLit (1975 to 2009) in order to identify trials for inclusion in this review.In this update we searched the following electronic databases in May 2012: Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 5, 2012), MEDLINE (2009 to May week 4 2012), and EMBASE (2009 to 2012 week 21) in order to identify trials for inclusion in the review. SELECTION CRITERIA: The review was restricted to randomized controlled trials (RCTs) that compared use of WBRT plus SRS versus WBRT alone for upfront treatment of adult patients with newly diagnosed metastases (single or multiple) in the brain resulting from any primary, extracranial cancer. DATA COLLECTION AND ANALYSIS: The Generic Inverse Variance method, random-effects model in RevMan 5 was used for the meta-analysis. MAIN RESULTS: A meta-analysis of two trials with a total of 358 participants, found no statistically significant difference in overall survival (OS) between WBRT plus SRS and WBRT alone groups (hazard ratio (HR) 0.82; 95% confidence interval (CI) 0.65 to 1.02). For patients with one brain metastasis median survival was significantly longer in WBRT plus SRS group (6.5 months) versus WBRT group (4.9 months; P = 0.04). Patients in the WBRT plus SRS group had decreased local failure compared to patients who received WBRT alone (HR 0.27; 95% CI 0.14 to 0.52). Furthermore, a statistically significant improvement in performance status scores and decrease in steroid use was seen in the WBRT plus SRS group. Unchanged or improved Karnofsky Performance Scale (KPS) at 6 months was seen in 43% of patients in the combined therapy group versus only 28% in WBRT group (P = 0.03). Overall, risk of bias in the included studies was unclear. AUTHORS' CONCLUSIONS: Since the last version of this review no new studies were found that met the inclusion criteria. Given the unclear risk of bias in the included studies, the results of this analysis have to be interpreted with caution. Analysis of all included patients, SRS plus WBRT, did not show a survival benefit over WBRT alone. However, performance status and local control were significantly better in the SRS plus WBRT group. Furthermore, significantly longer OS was reported in the combined treatment group for recursive partitioning analysis (RPA) Class I patients as well as patients with single metastasis.

The effect of centralization of caseload for primary brain tumor surgeries: trends from 2001-2007.

BACKGROUND: Improved patient outcomes have been associated with high-caseload hospitals for a multitude of conditions. This study analyzed adult patients undergoing surgical resection or biopsy of primary brain tumors. The aim of this study is two-fold: (1) to evaluate whether the trend towards centralization of primary brain tumor care in the US has continued during the period of between 2001 and 2007, and (2) to analyze volume-outcome effects. METHODS: Surgical volume trends of adults undergoing resection/biopsy of primary supratentorial brain tumors were analyzed using the Nationwide Inpatient Sample. High- and low-caseload hospitals were defined as those performing in the highest and lowest quintile of procedures, respectively. Length of stay (LOS), mortality and discharge disposition were the main outcomes of interest. RESULTS: NIS estimated 124,171 patients underwent resection/biopsy of primary supratentorial brain tumors between 2001 and 2007 in the US. The average number of annual resections in the highest 2 % and lowest 25 % caseload hospitals were 322 and 12 cases, respectively. Surgeries in high-caseload hospitals increased by 137 %, while those in low-caseload centers declined by 16.0 %. Overall, mortality decreased 35 %, with a reduction of 45 % in high- (from 2.2 % to 1.2 %) and 19 % in low- (from 3.2 % to 2.6 %) caseload hospitals. High-caseload centers had lower LOS than hospitals with lower caseload centers (6.4 vs. 8.0 days, p < 0.001). Multivariate analysis showed that patients treated in low-volume hospitals had an increased risk of death (OR 1.8, CI: 1.2-2.7, p = 0.006) and adverse discharge (OR 1.4, CI: 1.1-1.7, p = 0.01). CONCLUSIONS: Neurosurgical caseload at the nation's high volume craniotomy centers has continued to rise disproportionately, while low-caseload centers have seen a decrease in overall surgical volume. Over the time period between 2001 and 2007 there was a trend towards improved in-hospital mortality, LOS and discharge disposition for all hospitals; however, the trend is convincingly favorable for high-caseload hospitals.

The effect of transfer and hospital volume in subarachnoid hemorrhage patients.

INTRODUCTION: Prompt management of aneurysmal subarachnoid hemorrhage (SAH) is critical. Literature is inconclusive regarding outcomes for patients directly admitted to specialized centers versus transferred from lower-volume hospitals. Providers are often unclear about the safety of transferring critical patients. This study evaluated the "transfer effect" in a large sample of aneurysmal SAH patients undergoing treatment. METHODS: Using Nationwide Inpatient Sample 2002-2007 data, we analyzed outcomes of SAH patients treated with coil or clip procedures. Analyses studied the effect of direct-admit versus transfer admission on mortality, discharge disposition, complications, length of stay (LOS), and total charges. RESULTS: Of 47,114 patients, 31,711 (67.3 %) were direct-admits and 15,403 (32.7 %) were transfers. More transfer patients were coiled than direct-admits (45.3 vs. 33.7 %, p < 0.0001) and fewer underwent ventriculostomy (26.6 vs. 31.5 %, p = 0.003). Older age (OR 1.2, p < 0.0001), higher disease severity (OR 1.4, p < 0.0001), lower volume (OR 1.5, p < 0.0001), and ventriculostomy (OR 2.1, p < 0.0001) increased mortality and predicted non-routine discharge, complications, LOS, and charges. Transfer patients had similar mortality (OR 0.9, p = 0.13) and complications (OR 0.9, p = 0.22) as direct-admits, but incurred higher non-routine discharge (OR 1.3, p = 0.002). Analysis of grade V patients demonstrated similar outcomes between direct-admits and transfers; however, charges for treating transfer patients were notably higher ($401,386 vs. $242,774, p = 0.03). CONCLUSION: Patients treated in the lowest volume hospitals were 1.6 times more likely to die than those treated at the highest quintile hospitals. Among the critically ill grade V patients, transfer to higher-volume specialized centers did not increase the likelihood of a poor prognosis.

Comparative assessment of corticotomy facilitated rapid canine retraction using piezo versus bur: A randomized clinical study.

PURPOSE: The leading concern of orthodontic patients is prolonged treatment with fixed appliances and demand speedy treatment from the orthodontists. Piezocision is a relatively innovative, safe and reliable technique of corticotomy in the domain of surgically-accelerated orthodontic treatment. Our aim was to compare the efficiency of piezo corticotomy (piezocision) and conventional bur in rapid orthodontic tooth movement (OTM). SUBJECTS AND METHOD: The study employed a randomized, double-blind, split-mouth design. 24 subjects with Class II div 1 malocclusion were randomly assigned to the two interventions, viz; piezo and bur group. The primary parameters evaluated were the rate and amount of tooth movement and total treatment time required for canine retraction. Additionally, the duration of surgery and postoperative complications were also evaluated. OBSERVATIONS AND RESULTS: Rate and amount of tooth movement were significantly higher with reduction in total treatment time in piezo compared to bur group. The duration of surgery was significantly longer in piezo group with no significant difference observed in post-operative complications. CONCLUSION: Piezo-guided corticotomy was effective in providing rapid OTM with profound reduction in total treatment time and may be proposed as a suitable adjuvant to conventional corticotomy having comparable post-operative complications.

A Phase I Study of Autologous Dendritic Cell Vaccine Pulsed with Allogeneic Stem-like Cell Line Lysate in Patients with Newly Diagnosed or Recurrent Glioblastoma.

PURPOSE: Glioblastoma (GBM) is a heterogeneous malignancy with multiple subpopulations of cancer cells present within any tumor. We present the results of a phase I clinical trial using an autologous dendritic cell (DC) vaccine pulsed with lysate derived from a GBM stem-like cell line. PATIENTS AND METHODS: Patients with newly diagnosed and recurrent GBM were enrolled as separate cohorts. Eligibility criteria included a qualifying surgical resection or minimal tumor size, ≤ 4-mg dexamethasone daily dose, and Karnofsky score ≥70. Vaccine treatment consisted of two phases: an induction phase with vaccine given weekly for 4 weeks, and a maintenance phase with vaccines administered every 8 weeks until depletion of supply or disease progression. Patients with newly diagnosed GBM also received standard-of-care radiation and temozolomide. The primary objective for this open-label, single-institution trial was to assess the safety and tolerability of the autologous DC vaccine. RESULTS: For the 11 patients with newly diagnosed GBM, median progression-free survival (PFS) was 8.75 months, and median overall survival was 20.36 months. For the 25 patients with recurrent GBM, median PFS was 3.23 months, 6-month PFS was 24%, and median survival was 11.97 months. A subset of patients developed a cytotoxic T-cell response as determined by an IFNγ ELISpot assay. CONCLUSIONS: In this trial, treatment of newly diagnosed and recurrent GBM with autologous DC vaccine pulsed with lysate derived from an allogeneic stem-like cell line was safe and well tolerated. Clinical outcomes add to the body of evidence suggesting that immunotherapy plays a role in the treatment of GBM.