Malignant brainstem gliomas in adults: clinicopathological characteristics and prognostic factors.

Adult malignant brainstem gliomas (BSGs) are poorly characterized due to their relative rarity. We have examined histopathologically confirmed cases of adult malignant BSGs to better characterize the patient and tumor features and outcomes, including the natural history, presentation, imaging, molecular characteristics, prognostic factors, and appropriate treatments. A total of 34 patients were identified, consisting of 22 anaplastic astrocytomas (AAs) and 12 glioblastomas (GBMs). The overall median survival for all patients was 25.8 months, with patients having GBMs experiencing significantly worse survival (12.1 vs. 77.0 months, p = 0.0011). The majority of tumors revealed immunoreactivity for EGFR (93.3 %) and MGMT (64.7 %). Most tumors also exhibited chromosomal abnormalities affecting the loci of epidermal growth factor receptor (92.9 %), MET (100 %), PTEN (61.5 %), and 9p21 (80 %). AAs more commonly appeared diffusely enhancing (50.0 vs. 27.3 %) or diffusely nonenhancing (25.0 vs. 0.0 %), while GBMs were more likely to exhibit focal enhancement (54.6 vs. 10.0 %). Multivariate analysis revealed confirmed histopathology for GBM to significantly affect survival (HR 4.80; 95 % CI 1.86-12.4; p = 0.0012). In conclusion, adult malignant BSGs have an overall poor prognosis, with GBM tumors faring significantly worse than AAs. As AAs and GBMs have differing imaging characteristics, tissue diagnosis may be necessary to accurately determine patient prognosis and identify molecular characteristics which may aid in the treatment of these aggressive tumors.

Endovascular treatment of a spinal dural arteriovenous malformation (DAVF).

We present a case of a patient with rapid loss of motor strength in his lower extremities. He became bedridden with bowel and bladder incontinence, and developed saddle anesthesia. MRI of the lumbar spine showed edema in the conus medullaris and multiple flow voids within the spinal canal. A spinal angiogram showed a dorsal Type I spinal AVF. This was treated successfully with Onyx 18 (eV3, Irvine, CA). The patient showed rapid post-procedure improvement, and at discharge from the hospital to a rehabilitation center he was fully ambulatory. At 3-year follow-up, the patient was found to ambulate without difficulty. He also had improved saddle anesthesia, and he was voiding spontaneously. There was no evidence of flow voids on repeat MRI of the lumbar spine. The video can be found here: http://youtu.be/SDYNIGNQIW8 .

Transcirculation balloon-assisted stent-supported coil embolization of a basilar tip aneurysm.

We present the case of a balloon-assisted, stent-supported coil embolization of a basilar tip aneurysm. Initially, a balloon extending from the basilar artery into the right PCA was placed. However, even with a more proximal purchase, coils were found to impinge on the left PCA. Subsequently, a transcirculation approach was performed, where the left posterior communicating artery was utilized as a conduit for balloon support and the coils were embolized from the ipsilateral vertebral artery. However, after this transcirculation approach was completed, there was a coil tail extruding from the aneurysm. The balloon was then removed over an exchange wire and a horizontal stent advanced, spanning the entire neck of the aneurysm, eliminating the extruded coil. The video can be found here: http://youtu.be/bMbtZoPnYvo .

Initial experience with extreme angle cervical screw for treatment of trauma and cervical spondylosis.

In this study, we have described our initial experience and surgical technique of extreme angle screw placement in the cervical and upper thoracic spine of a cohort of patients undergoing posterior fusion. This extreme angle screw facilitates rod placement without need for any coronal contouring of the rod or offset connectors despite the varied entry site locations for posterior instrumentation and the different trajectories and pathways of these screws. From ruary 2011 to July 2011, extreme angle screws were placed in twenty consecutive adult patients who underwent posterior cervical, occipital-cervical or cervical-thoracic fusions. The primary diagnosis was cervical spondylotic myelopathy (13), trauma (4), and pseudoarthrosis with stenosis (3). Eight patients had gross instability. A total of 196 screws were placed; half of the cases involved instrumentation at or within the C3-7 segments (10) and the others included constructs extending to occipital bone, C2, T1, or T2 (10). Of all twenty cases, there were no perioperative hardware complications. At long-term follow-up, two patients required reoperation, one for hardware failure and the other for single level symptomatic pseudoarthrosis. We conclude that extreme angle screw use in the posterior cervical spine provides an evolution in posterior instrumentation that maximizes the biomechanical strength of a construct, allows for easy rod placement, and may improve the restoration of sagittal alignment. Overall, extreme angle screws facilitate rod placement even for screws offset from the natural plane of the rod, thereby avoiding the need for coronal contouring or placement of offset connectors.

Adult primitive neuroectodermal tumors: the prognostic value of supratentorial location.

Primitive neuroectodermal tumors (PNETs) are tumors which primarily consist of undifferentiated round neuroepithelial cells. Central nervous system PNETs can be divided into two genetically distinct groups: infratentorial PNET (iPNET)/medulloblastoma and supratentorial PNET (sPNET). Currently, the comparative outcome of adult patients with sPNETs and iPNETs is unknown. In this study we have utilized the Surveillance, Epidemiology, and End Results database to perform a comparative analysis of 103 cases of adult sPNET and 669 adult medulloblastoma cases. Additionally we have analyzed various factors to identify their prognostic significance and characterize the optimal treatment for these tumors. Patients with sPNETs were seen to have a significantly worse survival than those diagnosed with medulloblastomas (16 vs. 155 months, p < 0.0001). Elderly patients (15 vs. 114 months, p < 0.0001) and those over the age of 40 (68 vs. 147 months, p < 0.0001) experienced significantly worse survival than younger patients. In contrast, radiotherapy (143 vs. 26 months, p < 0.0001), surgical resection (116 vs. 22 months, p = 0.0010) and the extent of resection (EOR) (173 vs. 81 months, p = 0.0005) resulted in significantly improved patient survival. Multivariate analysis revealed age greater than 40 years (HR: 1.57; 95 % CI: 1.17-2.11; p = 0.0028) and sPNET pathology (HR: 3.41; 95 % CI: 2.47-4.72; p < 0.0001) to be poor prognostic factors for survival while radiotherapy (HR: 0.52; 95 % CI: 0.38-0.71; p < 0.0001) and the EOR (HR: 0.73; 95 % CI: 0.55-0.96; p = 0.023) were associated with significantly improved survival. The treatment of sPNETs should therefore include maximal surgical resection when feasible followed by radiotherapy as these treatments have been demonstrated to confer a survival benefit. Additional studies are needed to identify effective chemotherapeutics and specific treatment regimens for adults with sPNETs.

Improved survival in the largest national cohort of adults with cerebellar versus supratentorial low-grade astrocytomas.

OBJECT: Low-grade gliomas (LGGs) are indolent tumors that have the potential to dedifferentiate into malignant high-grade tumors. Recent studies have demonstrated that cerebellar low-grade tumors have a better prognosis than supratentorial tumors, although no study has focused on the risk factors for poor prognosis in cerebellar LGGs in adults. The authors of the current study aimed to address both of these concerns by using a large cohort derived from a national cancer registry and a smaller cohort derived from their institution's experience. METHODS: Adults with diagnosed Grade I and Grade II gliomas of the cerebellum were identified in the Surveillance, Epidemiology, and End Results (SEER) database. Multivariate Cox proportional hazard models were used to predict rates of survival, and the log-rank test was applied to evaluate differences in Kaplan-Meier survival curves. An institutional cohort was created by isolating all patients whose surgical pathology revealed an LGG of the cerebellum. Excluded from analysis were patients in whom a glioma was first diagnosed under the age of 18 years and those whose tumors could not be definitively determined to arise from the cerebellum. Results Data from the local cohort (11 patients) demonstrated that the most common presenting symptom was headache, which occurred in more than 70% of the cohort. Approximately half of the patients in this cohort had symptomatic improvement after treatment. RESULTS: from the SEER cohort (166 patients) revealed that adults with Grade I gliomas were slightly younger than those with Grade II tumors (p < 0.01), but no other demographic differences were observed. Patients with Grade I tumors were twice as likely to undergo gross-total resection (54% vs 21%), and those with Grade II gliomas were much more likely to receive postoperative radiation (3% vs 48%). Five-year survival was greater in the patients with Grade I gliomas than in those with Grade II lesions (91% vs 70%). Multivariate analysis revealed that an age ≥ 40 years (HR 7.30, 95% CI 3.55-15.0, p < 0.0001) and Grade II tumors (HR 2.76, 95% CI 1.12-6.84, p = 0.028) were risk factors for death, whereas female sex was protective (HR 0.28, 95% CI 0.14-0.59, p < 0.001). Log-rank tests revealed that a cerebellar location was protective (p < 0.0001), but this relationship was only true for Grade II tumors (p < 0.0001). Survival in patients with Grade I gliomas was not different based on the various lesion locations (p = 0.21). CONCLUSIONS: Taken together, adults with cerebellar WHO Grade I and II astrocytomas have a much more favorable survival curve than those with similar supratentorial tumors. Research demonstrates that the primary driver of this phenomenon is the improved survival in patients with cerebellar Grade II gliomas.

Cerebellopontine angle meningiomas: postoperative outcomes in a modern cohort.

OBJECT: Tumors of the cerebellopontine angle (CPA) have always proven difficult for neurosurgeons to optimally manage. Studies investigating the natural history and treatment of vestibular schwannomas have dominated the literature in this regard. Distinguishing meningiomas from schwannomas in this location carries particular importance as each tumor type has certain prognostic and surgical considerations. In this study, the authors have characterized the outcomes of 34 patients surgically treated for CPA meningiomas and have investigated various factors that may affect postoperative neurological function. METHODS: The medical records of patients with CPA meningiomas who underwent surgery from 2005 to 2013 at the Duke University Health System were reviewed. Various patient, clinical, and tumor data were gathered from the medical records including patient demographics, pre- and postoperative neurological examinations, duration of symptoms, procedural details, tumor pathology and size, and treatment characteristics. Differences in continuous variables were then analyzed using the Student t-test while categorical variables were evaluated using the chi-square test. RESULTS: A total of 34 patients underwent surgical treatment for CPA meningiomas during the 8-year period. Jugular foramen invasion was seen in 17.6% of tumors, with nearly half (41.2%) extending into the internal acoustic canal. The most common presenting symptom was hearing loss (58.8%), followed by headache (52.9%) and facial numbness/pain (50.0%). The most common cranial nerve (CN) affected was CN X (11.8%), followed by CNs VI and VII (5.9%). Postoperatively, no patients experienced a decrease in hearing, with only 5.9% of patients experiencing facial nerve palsies. Patients with tumors larger than 3 cm had a significantly higher incidence of permanent CN deficits than those with smaller tumors (45.5% vs 5.9%, respectively; p = 0.011). Also, tumor extension into the jugular foramen was associated with the occurrence of lower CN deficits, none of which occurred in tumors without jugular foramen invasion. Internal acoustic canal tumor extension was not seen to be associated with postoperative complications or CN deficits. CONCLUSIONS: Meningiomas of the CPA are challenging lesions to treat surgically. However, the risk of facial palsy and hearing loss is significantly lower when compared with vestibular schwannomas. Novel methods for preoperative differentiation are needed to appropriately counsel patients on surgical risks. Also, due to the significant potential for neurological deficits, further studies are needed to investigate the utility of radiotherapy for these lesions.

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.

Outcomes and complications following spinous process fixation: a single-center analysis of 192 cases.

Spinous process fixation (SPF) is presented as less invasive than pedicle screws. There has been little quantitative data to support this assertion, and "minimally invasive" has not been well defined in spine surgery. Length of stay (LOS) and blood loss (BL) were chosen as surrogate measures of "minimally invasive." A chart review was conducted on 192 lumbar fusion patients (374 levels). A backward-selection multiple-linear-regression was performed to determine what variables contribute to LOS and estimated blood loss (EBL). A logistic regression controlling for age and number of levels on complication rates was also performed. Number of levels with supplementary screw fixation (SSF) was significantly associated with LOS (p = 0.003). Controlling for number of surgical levels, LOS increased by 0.30 days (95% CI: 0.02-0.58) for each level with SSF. For each additional level including SSF, BL increases by 25.31 cc (95% CI: 3.50-47.12, p = 0.023). Interbody fusion increases blood loss by 68.16 cc (95% CI: 17.18-119.13, p = .009). For each additional level with SSF, odds of perioperative complications increase by OR = 2.34 (95% CI: 1.35-4.05). Long-term complications were not affected by instrumentation. LOS and BL are increased in patients with SSF vs. SPF only. Odds of perioperative complications are increased in patients with SSF relative to those treated with SPF alone.

Thrombin and hemin as central factors in the mechanisms of intracerebral hemorrhage-induced secondary brain injury and as potential targets for intervention.

Intracerebral hemorrhage (ICH) is a subtype of stoke that may cause significant morbidity and mortality. Brain injury due to ICH initially occurs within the first few hours as a result of mass effect due to hematoma formation. However, there is increasing interest in the mechanisms of secondary brain injury as many patients continue to deteriorate clinically despite no signs of rehemorrhage or hematoma expansion. This continued insult after primary hemorrhage is believed to be mediated by the cytotoxic, excitotoxic, oxidative, and inflammatory effects of intraparenchymal blood. The main factors responsible for this injury are thrombin and erythrocyte contents such as hemoglobin. Therapies including thrombin inhibitors, N-methyl-D-aspartate antagonists, chelators to bind free iron, and antiinflammatory drugs are currently under investigation for reducing this secondary brain injury. This review will discuss the molecular mechanisms of brain injury as a result of intraparenchymal blood, potential targets for therapeutic intervention, and treatment strategies currently in development.

Prognostic Factors and Treatment of Spinal Astrocytomas: A Multi-institutional Cohort Analysis.

STUDY DESIGN: Retrospective cohort analysis of patients with spinal astrocytoma from multi-institutional data and the literature. OBJECTIVE: To determine the prognostic factors, treatment, and survival of patients. SUMMARY OF BACKGROUND DATA: Our current understanding of the epidemiology, prognosis, and optimal treatment of spinal astrocytoma is limited. The literature is confined to case reports or small institutional case series. METHOD: Patient demographics, tumor characteristics, treatments, and outcomes were extracted. Univariate Kaplan-Meier survival analysis was performed to identify prognostic factors followed by multivariate Cox proportional hazard analysis. Wilcoxon signed-rank test was performed on pre- and postoperational functional status as measured by McCormick score. RESULTS: Ninety-four patients from four institutions and 339 patients from the literature were included. For the multi-institutional cohort, WHO grade IV tumors had shorter progression-free survival (PFS) than those of lower grades, whereas gross total resection (GTR) (hazard ratio [HR]: 0.41, 95% confidence interval [CI]: 0.14-1.27, P = 0.124) trended toward longer PFS when compared to subtotal resection (STR). Age 18 years or older, paresthesia as a presenting symptom, and higher WHO grade were associated with shorter overall survival (OS), whereas thoracic tumor location when compared to cervical tumor location, biopsy when compared to STR, and radiotherapy (HR: 0.42, 95% CI: 0.20-0.88, P = 0.022) were associated with longer OS. For the literature cohort, GTR (HR 0.43, 95% CI: 0.24-0.77, P = 0.005) was associated with longer PFS when compared to STR, whereas higher WHO grade was associated with shorter PFS. Higher WHO grade and recurrence/progression were associated with shorter OS. Postoperative McCormick score was significantly higher than preoperative score (P < 0.001), but subgroup analysis of the change in McCormick score by extent of resection revealed no differences among groups (P = 0.551). CONCLUSION: In patients with spinal astrocytomas, GTR likely resulted in longer PFS when compared to STR. Adjuvant radiotherapy appears to be effective in improving survival outcomes for high-grade tumors. LEVEL OF EVIDENCE: 4.

The effect of multifunctional polymer-based gels on wound healing in full thickness bacteria-contaminated mouse skin wound models.

We determined whether a two-part space-conforming polyethylene glycol/dopa polymer-based gel promoted healing of contaminated wounds in mice. This silver-catalysed gel was previously developed to be broadly microbiocidal in vitro while being biocompatible with human wound cell functioning. Full-thickness wounds were created on the backs of mice. The wounds were inoculated with 10(4) CFU of each of four common skin wound contaminants, Staphylococcus aureus, Pseudomonas aeruginosa, Acinetobacter baumanii and Clostridium perfringens. The wounds were then treated with our multifunctional polymer-based gel, the commercially available NewSkin product, or left to heal untreated. The untreated wounds were overtly infected, and presented detectable bacterial loads over the entire 21-day healing period, while the gel and NewSkin groups presented significantly smaller rises in bacterial levels and were cleared of detectable colonies by the third week, with the gel group clearing the bacteria earlier. While all three groups healed their wounds, the polymer-based gel-treated group demonstrated significantly earlier re-epithelialization and dermal maturation (P<0.05). This was reflected in a quick regain of tensile strength. This accelerated dermal maturation and regain in strength was noted in mice treated with the polymer-based gel when compared to wound treated with the commercially available Aquacel-Ag dressing (P<0.05). What distinguishes the polymer-based gel from these other products is that it is incorporated within the healing wound. These preclinical studies show that the anti-microbial polymer gel not only supports but also accelerates healing of bacterially contaminated wounds.

Management of Glioblastoma Multiforme in Elderly Patients: A Review of the Literature.

Glioblastoma multiforme (GBM) is the most common primary malignant brain tumor in adults, occurs most commonly in individuals older than 65 years of age, and is universally fatal. Increasing age compounds the poor prognosis of GBM, as elderly patients have markedly worse outcomes than younger patients. However, many of the studies previously investigating optimal treatment regimens exclude patients older than the age of 65 years and thus may not represent the best approaches to ensuring prolonged survival with preserved quality of life. This review aims to highlight the current literature on surgical and medical management, including our own experience, for GBM in the elderly patients, and to provide rational treatment approaches for a vulnerable, often-overlooked, patient population.

Enhancing the role of private practitioners in tuberculosis prevention and care activities in India.

India accounts for the highest number of incident tuberculosis (TB) cases globally. Hence, to impact the TB incidence world over, there is an urgent need to address and accelerate TB control activities in the country. Nearly, half of the TB patients first seek TB care in private sector. However, the participation of private practitioners (PPs) has been patchy in TB prevention and care and distrust exists between public and private sector. PPs usually have varied diagnostic and treatment practices that are inadequate and amplify the risk of drug resistance. Hence, their regulation and involvement as key stakeholders are important in TB prevention and care in India if we are to achieve TB control at global level. However, there remain certain barriers and gaps, which are preventing their upscaling. The current paper aims to discuss the status of private sector involvement in TB prevention and care in India. The paper also discusses the strategies and initiatives taken by the government in this regard as evidence shows that the involvement of private sector in co-opting directly observed treatment short-course (DOTS) helps to enhance case finding and treatment outcomes; it improves the accessibility of quality TB care with greater geographic coverage. Besides public-private mix, DOTS has been found more cost-effective and reduces financial burden of patients. The paper also offers to present some more solutions both at policy and program level for upscaling the engagement of PPs in the national TB control program.

Comparing outcomes of early, late, and non-surgical management of intraspinal abscess.

Intraspinal abscesses (ISAs) are rare lesions that are often neurologically devastating. Current treatment paradigms vary widely including early surgical decompression, drainage, and systemic antibiotics, delayed surgery, and sole medical management. The National Inpatient Sample (NIS) database was queried for cases of ISA from 2003 to 2012. Early and late surgery were defined as occurring before or after 48h of admission. Outcome measures included mortality, incidence of major complications, length of stay (LOS), and inpatient costs. A total of 10,150 patients were included (6281 early surgery, 3167 delayed surgery, 702 medical management). Paralysis, the main comorbidity, was most associated with early surgery (p<0.0001). In multivariate analysis, the rates of postoperative infection and paraplegia were highest with early surgery (p<0.0001), but the incidence of sepsis was higher with delayed surgery (p<0.0001). Early surgery was least associated with in-hospital mortality (p=0.0212), sepsis (p<0.001), and had the shortest LOS (p<0.001). Charges were highest with delayed surgery, and least with medical management (p<0.001). Medical management was associated with lower rates of complications (p<0.001). This is the largest study of patients with ISAs ever performed. Our results suggest that patients with ISAs undergoing surgical management have better outcomes and lower costs when operated on within 48h of admission, emphasizing the importance of accurate and early diagnosis of ISA.

Antimicrobial activities of silver used as a polymerization catalyst for a wound-healing matrix.

Wound healing is a complex and orchestrated process that re-establishes the barrier and other functions of the skin. While wound healing proceeds apace in healthy individual, bacterial overgrowth and infection disrupts this process with significant morbidity and mortality. As such, any artificial matrix to promote wound healing must also control infecting microbes. We had earlier developed a two-part space-conforming gel backbone based on polyethyleneglycol (PEG) or lactose, which used ionic silver as the catalyst for gelation. As silver is widely used as an in vitro antimicrobial, use of silver as a catalyst for gelation provided the opportunity to assess its function as an anti-microbial agent in the gels. We found that these gels show bacteriostatic and bactericidal activity for a range of Gram-negative and Gram-positive organisms, including aerobic as well as anaerobic bacteria. This activity lasted for days, as silver leached out of the formed gels over a day in the manner of second-order decay. Importantly the gels did not limit either cell growth or viability, though cell migration was affected. Adding collagen I fragments to the gels corrected this effect on cell migration. We also found that the PEG gel did not interfere with hemostasis. These observations provide the basis for use of the gel backbones for incorporation of anesthetic agents and factors that promote wound repair. In conclusion, silver ions can serve dual functions of catalyzing gelation and providing anti-microbial properties to a biocompatible polymer.

Glioblastoma in the elderly: the effect of aggressive and modern therapies on survival.

OBJECTIVE: The prognosis of elderly patients with glioblastoma (GBM) is universally poor. Currently, few studies have examined postoperative outcomes and the effects of various modern therapies such as bevacizumab on survival in this patient population. In this study, the authors evaluated the effects of various factors on overall survival in a cohort of elderly patients with newly diagnosed GBM. METHODS: A retrospective review was performed of elderly patients (≥ 65 years old) with newly diagnosed GBM treated between 2004 and 2010. Various characteristics were evaluated in univariate and multivariate stepwise models to examine their effects on complication risk and overall survival. RESULTS: A total of 120 patients were included in the study. The median age was 71 years, and sex was distributed evenly. Patients had a median Karnofsky Performance Scale (KPS) score of 80 and a median of 2 neurological symptoms on presentation. The majority (53.3%) of the patients did not have any comorbidities. Tumors most frequently (43.3%) involved the temporal lobe, followed by the parietal (35.8%), frontal (32.5%), and occipital (15.8%) regions. The majority (57.5%) of the tumors involved eloquent structures. The median tumor size was 4.3 cm. Every patient underwent resection, and 63.3% underwent gross-total resection (GTR). The vast majority (97.3%) of the patients received the postoperative standard of care consisting of radiotherapy with concurrent temozolomide. The majority (59.3%) of patients received additional agents, most commonly consisting of bevacizumab (38.9%). The median survival for all patients was 12.0 months; 26.7% of patients experienced long-term (≥ 2-year) survival. The extent of resection was seen to significantly affect overall survival; patients who underwent GTR had a median survival of 14.1 months, whereas those who underwent subtotal resection had a survival of 9.6 months (p = 0.038). Examination of chemotherapeutic effects revealed that the use of bevacizumab compared with no bevacizumab (20.1 vs 7.9 months, respectively; p < 0.0001) and irinotecan compared with no irinotecan (18.0 vs 9.7 months, respectively; p = 0.027) significantly improved survival. Multivariate stepwise analysis revealed that older age (hazard ratio [HR] 1.06 [95% CI1.02-1.10]; p = 0.0077), a higher KPS score (HR 0.97 [95% CI 0.95-0.99]; p = 0.0082), and the use of bevacizumab (HR 0.51 [95% CI 0.31-0.83]; p = 0.0067) to be significantly associated with survival. CONCLUSION: This study has demonstrated that GTR confers a modest survival benefit on elderly patients with GBM, suggesting that safe maximal resection is warranted. In addition, bevacizumab significantly increased the overall survival of these elderly patients with GBM; older age and preoperative KPS score also were significant prognostic factors. Although elderly patients with GBM have a poor prognosis, they may experience enhanced survival after the administration of the standard of care and the use of additional chemotherapeutics such as bevacizumab.

Radiation-induced malignant gliomas: a current review.

OBJECTIVE: Radiation-induced malignant gliomas (RIMGs) are known uncommon risks of brain irradiation. We describe 4 cases of RIMG that occurred at our institution and conduct the largest comprehensive review of the literature to characterize RIMGs better. METHODS: Patients were identified through the PubMed database. Pearson R linear correlation test was used to evaluate the correlation between radiotherapy (RT) dose and age and latency period. Student t test was used to evaluate differences between latency periods for original tumor lesions. A normalized biologic equivalent dose analysis was performed to indicate the minimum and maximum radiation threshold for neoplasia. A Kaplan-Meier analysis was used to illustrate the overall survival curves. RESULTS: The analysis included 172 cases from the PubMed database and 4 cases occurring at our institution. The median RT dose administered was 35.6 Gy, with the most common dosage ranges being 21-30 Gy (31%) and 41-50 Gy (21.5%). Median latency period was 9 years until diagnosis of RIMG, and RIMG occurred within 15 years in 82% of the patients. There was no correlation between the age of the patient at the time RT was administered (R(2) = 0.00081) or amount of RT (R(2) = 0.00005) and latency period for RIMG. The mean biologic equivalent dose for neoplasia of a RIMG was 63.3 Gy. The median survival of patients with RIMG improved over time (P = 0.004), with median survival of 9 months before 2007 and 11.5 months after 2007. CONCLUSIONS: The risk of RIMG appears to be the same for all age groups, histologies, and RT dosages. Although the risk is low, patients should be aware of RIMG as a possible complication of brain irradiation.

Spinal cord astrocytomas: a modern 20-year experience at a single institution.

STUDY DESIGN: Retrospective cohort analysis. OBJECTIVE: To examine the effect of resection on survival and neurological outcome in a modern cohort of patients with spinal cord astrocytomas and identify prognostic factors for survival. SUMMARY OF BACKGROUND DATA: There are currently no clear treatment guidelines for the management of spinal cord astrocytomas. Additionally there is no conclusive evidence for the surgical resection of these tumors, with some studies even demonstrating worse survival with surgery. However, most studies have examined patients treated prior to the routine use of magnetic resonance imaging and advanced microsurgical techniques. METHODS: We performed a retrospective review of 46 consecutive patients with spinal cord astrocytomas treated at our institution from 1992 to 2012. Univariate and multivariate analyses were used to identify variables associated with survival. RESULTS: The majority of patients (67.4%) underwent surgical resection, with the remaining only receiving biopsy. Of those who underwent resection, only 12.5% of patients underwent gross total resection, all of whom had low-grade astrocytomas. Of all patients, 30.7% worsened compared with their preoperative baseline. The occurrence of worsening increased with high tumor grade (52.9% vs. 27.6%, P = 0.086) and an increased extent of resection (66.7% vs. 18.8%, P = 0.0069). Resection did not provide a survival benefit compared with biopsy alone (P = 0.53). Multivariate analysis revealed high-grade histology (hazard ratio, 11.3; 95% confidence interval, 2.41-53.2; P = 0.0021), tumor dissemination (hazard ratio, 4.24; 95% confidence interval, 1.22-14.8; P = 0.023), and an increasing number of tumor involved levels (hazard ratio, 1.31; 95% confidence interval, 0.99-1.74; P = 0.058) to be associated with worse survival. CONCLUSION: As surgical intervention is associated with a higher rate of neurological complications and lacks a clear benefit, the resection of spinal cord astrocytomas should be reserved for select cases and should be used sparingly.