Overexpression of tissue microRNA10b may help predict glioma prognosis

We investigated the relationship between microRNA-10b (miR-10b) expression and prognosis in human glioma patients. Quantitative real-time polymerase chain reaction (qRT-PCR) analysis was used to characterize the expression patterns of miR-10b in 128 glioma and 20 normal brain tissues. Clinical information – age, sex, Karnofsky Performance Status (KPS) and World Health Organization (WHO) grade – were also collected. The associations between miR-10b expression and the clinicopathological factors and outcome of glioma patients were statistically analyzed. Expression levels of miR-10b in glioma tissue were significantly higher than in normal brain tissue (P < 0.001). High-grade glioma (WHO grade III and IV) had much higher miR-10b expression levels than low-grade tumors (WHO grade I and II). Additionally, the increased miR-10b expression in the glioma tissues was significantly associated with a low KPS (P = 0.03). Kaplan–Meier survival curves and Cox regression analyses showed that overexpression of miR-10b (P = 0.01) and high grade (P = 0.02) were independent factors predicting poor outcome for glioma patients. Furthermore, subgroup analyses showed that the miR-10b expression level was significantly associated with poor overall survival in glioma patients with high grades (P < 0.001). Up-regulation of miR-10b may have value in predicting clinical outcome in glioma patients, particularly for those with high pathological grades.     

Spinal ependymomas: Benefits of extent of resection for different histological grades

Although the World Health Organization (WHO) categorizes spinal ependymomas into three histological grades, difference in surgical outcomes between WHO grades I and II tumors are unclear. For these benign tumors, prognosis may be best determined by factors other than tumor grade alone, such as extent of resection. To analyze the effects of the extent of resection on different grades of spinal ependymomas, we performed a comprehensive literature review to identify adult spinal ependymoma patients who received surgical resection with a clearly identifiable WHO grade. A total of 175 patients were identified. While grade III tumors carried the worst prognosis as expected (p < 0.001), grade I and II tumors did not differ significantly in outcomes following surgery. Overall, gross total resection (GTR, 68.7%, 114/166) provided significantly improved progression-free survival (PFS, p < 0.001) and overall survival (OS, p = 0.022) compared to the subtotal resection group. Surprisingly, the highest GTR rate was achieved for grade II tumors (78.8%, 78/99; p < 0.001) followed by grade I (58.9%, 33/56) and grade III tumors (27.3%, 3/11). Interestingly, PFS was significantly improved by GTR for grade II tumors (p < 0.001), but not for grade I (p = 0.705). Similar trends, although not statistically significant, were found for OS. Our results show that while GTR provides the best overall outcomes, GTR is most effective for classic grade II ependymomas, but not for grade I ependymomas. Despite having a lower WHO grade, myxopapillary ependymomas have a lower GTR rate, and benefit less from GTR.     

Co-expression of midkine and pleiotrophin predicts poor survival in human glioma

The aim of this study was to investigate whether co-expression of midkine (MK) and pleiotrophin (PTN) has prognostic relevance in human gliomas. Immunohistochemistry was used to investigate the expression of MK and PTN proteins in 168 patients with gliomas. The levels of MK and PTN mRNA in glioma tissues and paratumor tissues were evaluated in 45 paired cases by quantitative real-time polymerase chain reaction (qRT-PCR). Kaplan–Meier survival analysis was performed to assess prognostic significance. The expression levels of MK and PTN proteins in glioma tissue were both significantly higher (both p < 0.001) than those in paratumor tissues on immunohistochemistry analysis, which was confirmed by qRT-PCR analysis. Additionally, the overexpression of either MK or PTN was significantly associated with the World Health Organization Grade (p = 0.001 and 0.034, respectively), low Karnofsky Performance Status (KPS) score (p = 0.022 and 0.001, respectively), time to recurrence (p = 0.043 and 0.011, respectively) and poor overall survival (p = 0.018 and 0.001, respectively). Multivariate Cox proportional-hazards regression analysis revealed that increased expressions of MK and PTN were both independent prognostic factors for poor overall survival (p = 0.030 and 0.022, respectively). Furthermore, the co-expression of MK and PTN was more significantly (p = 0.003) associated with adverse prognosis in patients with gliomas than the respective expression of MK or PTN alone. To our knowledge, these findings are the first to indicate that the co-expression of MK and PTN is significantly correlated with prognosis in glioma patients, suggesting that the co-expression of these proteins may be used as both an early diagnostic and independent prognostic marker.     

Downregulation of chromatin remodeling factor CHD5 is associated with a poor prognosis in human glioma

Chromodomain helicase DNA-binding protein 5 (CHD5), a member of the CHD family, is involved in key cellular processes including chromatin remodeling, cell cycle regulation, and cellular adhesion. Recent studies have demonstrated that CHD5 is the product of a novel tumor suppressor gene and is implicated in certain tumor types. However, the clinicopathological significance of CHD5 expression in human malignant gliomas remains unclear. To address this problem, CHD5 expression in human gliomas and non-neoplastic brain tissues was measured using real-time quantitative polymerase chain reaction (RT–PCR) assay, Western blot, and immunohistochemistry. The association of CHD5 immunostaining with clinicopathological factors or prognosis of glioma patients was statistically analyzed. Genetic and protein expression of CHD5 were downregulated in glioma tissues compared to corresponding non-neoplastic brain tissues (both p < 0.001). Additionally, decreased expression of CHD5 in glioma was significantly associated with pathological grade (p = 0.007); high pathological grade was associated with low CHD5 expression. Loss of CHD5 protein expression was also significantly correlated with a low Karnofsky performance scale score (p = 0.01). Moreover, overall survival of patients with low CHD5 protein expression was dramatically shorter than those of patients with high CHD5 protein expression (p = 0.003). Multivariate Cox regression analysis indicated that CHD5 expression was an independent prognostic factor for patients with gliomas (p = 0.01). In conclusion, these data offer convincing evidence for the first time that CHD5 might act as a tumor suppressor in glioma, may act as a regulator of aggressive development, and is a candidate prognostic marker for this malignancy.     

Ki-67 overexpression in WHO grade II gliomas is associated with poor postoperative seizure control

PurposeSeizures are the most common initial symptom in patients with low-grade gliomas, and approximately 30% of these patients still suffer from epilepsy after gross-total resection of the tumour. We examined the relationship between the overexpression of ki-67 in WHO grade II gliomas and seizure control.MethodsA series of 93 histologically confirmed WHO grade II glioma tissues were analysed through immunohistochemical staining for ki-67 expression. Follow-up visits regarding seizure control were scheduled at 12 months. The Engel classification was used to categorise patients’ seizure status.ResultsOf the 93 patients analysed, 65 (66.3%) patients initially presented with seizures. A total of 36 patients were diagnosed with WHO grade II oligodendrogliomas, 29 patients had oligoastrocytomas and 28 patients had astrocytomas. Ki-67 was over-expressed in 15 patients. One year after surgery poor seizure control was observed in 11 of these patients. In contrast, low ki-67 expression (<10%) was found in 78 patients. Poor seizure control was observed in 36 patients (difference between ki-67 over- and low expression groups P = 0.002). Logistic regression analysis revealed that patients with gross-total resection achieved better seizure control while ki-67 overexpression and age below 38 years were poor seizure control factors explained of the variance of seizure outcome (OR: 0.382, 4.354 and 1.822, respectively).ConclusionsIn WHO grade II gliomas, Ki-67 is a molecular marker which predicts poor seizure control of glioma patients after the resection of the tumour. Gross-total resection, ki-67 overexpression and age below 38 years significantly affect seizure prognosis.     

KPNA2 predicts long term survival in patients with anaplastic oligoastrocytomas

The family of karyopherins comprises importins and exportins which are both involved in nucleocytoplasmic shuttling. Increased levels of karyopherin a2/importin 1 (KPNA2) and chromosome region maintenance protein 1/exportin 1 (CRM1) have been associated with poorer prognosis in patients with infiltrative astrocytomas. Isocitrate dehydrogenase 1 gene (IDH1) R132H mutation status was also recently identified as a prognostic factor for malignant gliomas. We evaluated KPNA2 and CRM1, as well as the IDH1 mutation status, as possible novel biomarkers for World Health Organization grade III anaplastic oligoastrocytomas (AOA). We analyzed nuclear expression of KPNA2 by immunohistochemistry in 72 primary anaplastic gliomas (29 AOA, 24 anaplastic astrocytomas, 19 anaplastic oligodendrogliomas). The IDH1 mutation status was also determined in patients with anaplastic astrocytomas and AOA, and AOA patients were additionally evaluated for CRM1 nuclear expression. Long term survivors (LTS; >8 years) with AOA showed lower KPNA2 expression levels compared to non-LTS (p = 0.005). KPNA2 expression (⩾5% versus <5%, 1–<5%, median) was found to correlate inversely with overall survival (OS) and progression-free survival (PFS) in our overall series as well as in the AOA group (anaplastic gliomas: OS p = 0.017; PFS p = 0.033; AOA: OS p = 0.017, PFS p = 0.040). Mutant IDH1-R132H was detected in 69% of the AOA cohort; a combination of KPNA2 low expression and mutant IDH1-R132H was only seen in LTS (p = 0.050). No differences between the histological subtypes were observed in terms of KPNA2 expression and IDH1-R132H mutation status. To our knowledge this is the first time it has been shown that KPNA2 expression may have potential as a prognostic biomarker for AOA as well.     

Prognostic factors and survival in primary adult high grade brainstem astrocytoma: A population based study from 1973–2008

Adult brainstem astrocytomas are a rare and heterogeneous group of malignancies. Most reports represent low-grade gliomas. This study used the Surveillance, Epidemiology and End Results (SEER) database to analyze the association between survival and demographic factors, tumor histology, and treatment characteristics among adult patients with high-grade brainstem astrocytoma (HGBSA). Adult patients with histologically confirmed diagnoses of primary HGBSA were studied. In univariate and multivariate analysis, we investigated the effect of demographics, tumor histology and treatment modality on survival. Overall median survival in the cohort of 240 adult patients was 7 months, with 1, 2, 5 and 10 year survival rates of 33.2%, 19.7%, 10.1%, and 8.3%, respectively. Age >50 years (hazard ratio [HR] 1.98, 95% confidence interval [CI] 1.45–2.70, p < 0.001) and grade IV versus grade III tumor (HR 1.61, 95% CI 1.15–2.26, p = 0.006) were associated with statistically significant increased mortality in multivariate analyses. Surgical intervention trended toward association with lower mortality (HR 0.68, 95% CI 0.47–1.01, p = 0.055). Our findings suggest that in patients with HGBSA, younger age and lower-grade histology are associated with better prognosis. Surgical intervention trended towards a significant association with better outcome, while radiation treatment was not associated with a statistically significant benefit in survival.     

Trends in the presentation,surgical treatment,and outcomes of tethered cord syndrome: A nationwide study from 2001 to 2010

ObjectiveThis is a nationwide query into surgical management techniques for tethered cord syndrome, focusing on patient demographic, hospital characteristics, and treatment outcomes. Our hypothesis is that detethering vs. fusion for TCS results in different in-hospital complications.Materials and methodsRetrospective review of the Nationwide Inpatient Sample 2001–2010. Inclusion: TCS discharges undergoing detethering or fusion. Sub-analysis compared TCS cases by age (pediatric [≤9 years] vs. adolescent [10–18 year]). Independent t-tests identified differences between fusion and detethering for hospital-related and surgical factors; multivariate analysis investigated procedure as a risk factor for complications/mortality.Results6457 TCS discharges: 5844 detetherings, 613 fusions. Fusion TCS had higher baseline Deyo Index (0.16 vs. 0.06), procedure-related complications (21.3% vs. 7.63%), and mortality (0.33% vs. 0.09%) than detethering, all p < 0.001. Detethering for TCS was a significant factor for reducing mortality (OR 0.195, p < 0.001), cardiac (OR 0.27, p < 0.001), respiratory (OR 0.26, p < 0.001), digestive system (OR 0.32, p < 0.001), puncture nerve/vessel (OR 0.56, p = 0.009), wound (OR 0.25, p < 0.001), infection (OR 0.29, p < 0.001), posthemorrhagic anemia (OR 0.04, p = 0.002), ARDS (OR 0.13, p < 0.001), and venous thrombotic (OR 0.53, p = 0.043) complications. Detethering increased nervous system (OR 1.34, p = 0.049) and urinary (OR 2.60, p < 0.001) complications. Adolescent TCS had higher Deyo score (0.08 vs. 0.03, p < 0.001), LOS (5.77 vs. 4.13 days, p < 0.001), and charges ($54,592.28 vs. $33,043.83, p < 0.001), but similar mortality. Adolescent TCS discharges had increased prevalence of all procedure-related complications, and higher overall complication rate (11.10% vs. 5.08%, p < 0.001) than pediatric.ConclusionsWith fusion identified as a significant risk factor for mortality and multiple procedure-related complications in TCS surgical patients, this study could aid surgeons in counseling TCS patients to optimize outcomes.     

Traumatic interhemispheric subdural haematoma: Study of 35 cases

The clinical and radiological findings, management, and outcomes in 35 patients with traumatic interhemispheric subdural haematoma (ISH) were reviewed retrospectively. Twenty-five patients had favourable outcomes and 10 had poor outcomes. All patients were treated conservatively for ISH. Univariate analysis found that the Glasgow Coma Scale (GCS) score (p < 0.001), hypovolemic shock (p = 0.018), skull fracture (p = 0.008), convexity or posterior fossa subdural haematoma (p = 0.008), and subarachnoid haemorrhage (SAH) were correlated with outcome (p < 0.001). Multivariate analysis showed that GCS score (p = 0.031; odds ratio [OR], 0.6; 95% confidence interval [CI], 0.3–0.9) and the presence of SAH (p = 0.023; OR, 14.2; 95% CI, 1.5–138.2) were significantly related to poor outcome. This study provides important information on the clinicoradiological findings and prognoses in patients with traumatic ISH.     

In-hospital outcomes of aneurysmal subarachnoid hemorrhage associated with cocaine use in the USA

Cocaine use is associated with higher mortality in small retrospective studies of brain-injured patients. We aimed to explore in-hospital outcomes in a large population based study of aneurysmal subarachnoid hemorrhage (aSAH) with cocaine use. aSAH patients were identified from the 2007–2010 USA Nationwide Inpatient Sample using International Classification of Disease, Ninth Revision codes. Demographics, comorbidities and surgical procedures were compared between cocaine users and non-users. The primary outcomes were in-hospital mortality and home discharge/self-care. Secondary outcomes were vasospasm treated with angioplasty, hydrocephalus, gastrostomy and tracheostomy. There were 103,876 patients with aSAH. The cocaine group were younger (45.8 ± 9.8 versus 58.4 ± 15.8, p < 0.001), predominantly male (53.3% versus 38.5%, p < 0.001) and had a higher proportion of black patients (36.9% versus 11.5%, p < 0.001). The incidence of seizures was higher among cocaine users (16.2% versus 11.1%, p < 0.001). Endovascular coiling of intracranial aneurysms (24% versus 18.5%, p < 0.001) was more frequent in cocaine users. The univariate analysis showed higher rates of in-hospital mortality and vasospasm treated with angioplasty, but lower home discharge in the cocaine group. In the multivariate analysis, the cocaine cohort had higher in-hospital mortality (odds ratio [OR] 1.43, 95% confidence interval [CI] 1.27–1.61, p < 0.001) and lower home discharge rates (OR 0.79, 95% CI 0.69–0.87, p < 0.001) after adjusting for confounders. Rates of vasospasm treated with angioplasty however were similar between the two groups. Cocaine use was found to be independently associated with poor outcomes, particularly higher mortality and lower home discharge rates. Cocaine use however, was not associated with vasospasm that required treatment with angioplasty. Prospective confirmation is warranted.     

Symptom resolution in infiltrating WHO grade II-IV glioma patients undergoing surgical resection

Past studies of morbidity in patients with infiltrating gliomas have focused on the impact of surgery on quality of life. Surprisingly, little attention has been given to the rate at which the presenting symptoms improve after surgery, even though this is often the patient’s first concern. This study is an initial effort to provide useful information about symptom resolution and factors predicting persistence of symptoms in glioma patients who undergo surgery. We conducted a retrospective analysis on patients who underwent surgery for World Health Organization (WHO) grade II-IV astrocytoma/oligodendroglioma/oligoastrocytoma at our institution. All patients were seen 2–4 months postoperatively, and asked about the persistence of symptoms they experienced preoperatively. Symptoms reported in clinic were assessed against symptoms reported prior to surgery. Our study includes 56 consecutive patients undergoing surgery for gliomas. Of patients who experienced symptoms initially, headache resolved in 18/27 postoperatively, weakness resolved in 8/14 postoperatively, altered mental status resolved in 8/12 postoperatively, vision problems resolved in 7/11 postoperatively, nausea resolved in 5/7 postoperatively, and ataxia resolved in 4/5 postoperatively. Headache was more likely to resolve in patients with frontal or temporal tumors (p = 0.02). Preoperative Karnofsky Performance Scale (KPS) of 70 or less was associated with longer postsurgical hospital stay (p < 0.01). Younger patients were more likely to experience a resolution of altered mental status (p = 0.04). Our analysis provides data regarding the rate at which surgery alleviates patient symptoms and considers variables predicting likelihood of symptom resolution. Some patients will experience symptom resolution following resection of WHO grade II-IV gliomas in the months following surgery.     

Risk factors associated with short sleep duration among Chinese school-aged children

ObjectivesTo examine risk factors regarding short sleep duration among Chinese school-aged children.MethodsA random sample of 20,778 children aged around 5–11 years participated in a cross-sectional survey, which was conducted in eight cities of China in 2005. A parent-administered questionnaire was used to collect information on children’s sleep duration and possible related factors from eight domains. Short sleep duration was defined as total sleep duration <9 h per day.ResultsIn all, 28.3% of the sampled children slept <9 h per day. The multivariate logistic regression identified, after adjusting for demographic and socioeconomic variables, factors associated with short sleep duration: more television viewing during weekdays (OR = 1.21, p = 0.004), more frequent computer/internet using (OR = 1.17, p = 0.006), earlier school starting time (OR = 1.10, p = 0.020), more time on homework during weekdays (OR = 1.66, p < 0.001) and weekends (OR = 1.14, p = 0.001), poor bedtime hygiene (e.g., having drinks with caffeine after 6:00PM [OR = 1.22, p < 0.001], doing exciting activities during bedtime [OR = 1.16, p < 0.001], and irregular bedtime [OR = 1.55, p < 0.001]), and shorter sleep duration of parents (mother: OR = 1.31, p < 0.001 for sleep duration <6 h and OR = 1.24, p = 0.006 for 6–8 h; father: OR = 1.52, p < 0.001 for <6 h and OR = 1.19, p < 0.001 for 6–8 h).ConclusionsFactors associated with sleep duration covered multidimensional domains among school-aged children. Compared to sleep environments and chronic health problems, school schedules, lifestyle patterns, and parents’ sleep habits had greater impact on children’s sleep duration, indicating the existing chronic sleep loss in school children could be, at least partly, intervened by reducing the use of visual technologies, by changing the school schedules, by improving the sleep hygiene routine, and by regulating parents’ sleep habits.     

Treatment and survival of supratentorial and posterior fossa ependymomas in adults

Ependymoma is a rare primary brain or spinal cord tumor that arises from the ependyma, a tissue of the central nervous system. This study analyzed a large cohort of adult supratentorial and posterior fossa ependymoma tumors in order to elucidate factors associated with overall survival. We utilized the USA National Cancer Database to study adult World Health Organization grade II/III supratentorial and posterior fossa ependymoma patients treated between 1998 and 2011. Overall survival was estimated by the Kaplan–Meier method and factors associated with survival were determined using a multivariate Cox proportional hazards model. Among 1318 patients, 1055 (80.0%) had grade II and 263 (20.0%) anaplastic tumors located in the posterior fossa (64.3%) and supratentorial region (35.7%). Overall average age was 44.3 years, 48.0% of patients were female, 86.5% were Caucasian, and 36.8% underwent near/gross total surgical resection. Radiotherapy was given to 662 patients (50.8%) and 75 (5.9%) received chemotherapy. Older age at diagnosis (hazard ratio [HR] 1.51, p < 0.0001), high tumor grade (HR 1.82, p = 0.005), and large tumor size (HR 1.66, p = 0.008) were associated with poor survival. Females compared to males (HR 0.67, p = 0.03) and patients with posterior fossa tumors versus supratentorial (HR 0.64, p = 0.04) had a survival advantage. Our study showed that older patients, with supratentorial tumors, and high histological grade had an increased risk of mortality. A survival benefit was captured in females and patients with posterior fossa tumors. Adjuvant radiotherapy and chemotherapy did not confer a survival benefit among all patients, even after stratification by tumor grade or anatomical location.     

An analysis of 170 glioma patients and systematic review to investigate the association between IDH-1 mutations and preoperative glioma-related epilepsy

Seizure is a common presenting symptom of glioma, and many biomarkers have been suggested to be associated with preoperative seizure; however, the relationships between IDH (isocitrate dehydrogenase) mutations and glioma-related epilepsy only recently been studied. The authors aimed to examine the correlations between IDH mutations in glioma patients with preoperative seizures and tumor location. A series of 170 glioma samples were analyzed for IDH1 R132H mutations (amino acid change from arginine to histidine at codon 132) with immunohistochemistry (IHC) staining and for IDH mutations with direct DNA sequencing when the IHC results were negative. If either the IHC or direct DNA sequencing result was positive, the IDH status was defined as mutated. The results of the IDH mutation examinations were used to analyze the relationship between mutations and glioma-related epilepsy. The study population consisted of 64 (37.6%) World Health Organization (WHO) grade II gliomas, 58 (34.1%) grade III, and 48 (28.3%) grade IV gliomas. A total of 84 samples with IDH1 mutations were observed in our study, and 54 of these presented with seizures as the initial symptoms, whereas 28 of the patients with wild-type IDH status presented with seizures (p = 0.043 for the WHO grade II gliomas, p = 0.002 for the grade III gliomas and p = 0.942 for the grade IV gliomas, chi-squared tests). Among the WHO grade II and III gliomas, IDH1 mutations were significantly associated with preoperative seizures, but no significant relationship between IDH mutations and preoperative seizures was found with glioblastoma multiforme.     

Children diagnosed with autism spectrum disorder before or after the age of 6 years

This study compared children with early and late diagnosis of autism spectrum disorder (ASD). All children in four consecutive birth cohorts in Iceland diagnosed with ASD were divided into two groups based on their age at initial ASD diagnosis: 58 children were diagnosed before age 6 (group 1) and 41 children after age 6 (group 2). Children in group 1 were more likely to receive a diagnosis of childhood autism (p ≤ 0.001), their average IQ/DQ was lower (p < 0.001), verbal status was lower (p < 0.001), and a history of autistic regression was more common (p < 0.01) than in group 2. Half of the children in group 2 had received other developmental diagnoses prior to the ASD diagnosis, but this applied to only a few of the children in group 1 (p < 0.001). There was no difference between the groups with regard to autistic symptoms as measured by the Autism Diagnostic Interview-Revised (p = 0.224), frequency of associated medical conditions (p = 0.640), age of first parental concern (p = 0.244), and age of first autistic symptoms on hindsight (p = 0.540). The majority of parents (76.2%) had developmental concerns before age 3, and with hindsight 83.3% thought that autistic symptoms had been present before age 2.     

Hemangiopericytoma: Radical resection remains the cornerstone of therapy

Hemangiopericytomas (HPC) are mesenchymal tumors with a propensity towards chronicity and metastasis. This study aimed to reflect a single institution experience with both World Health Organization (WHO) grade II and III HPC. Pathology records from the years 1990–2013 at the University of Washington were searched to identify tumors unequivocally classified as HPC. Electronic chart review was then utilized to collect pertinent patient data. Of the WHO grade II HPC, there were four men and two women (average age 52 years) while the grade III HPC group had eight men and two women (average age 51 years). Sixty-six percent of WHO grade II tumors were located in the middle or posterior fossa as compared to none of the grade III tumors. Survival analysis revealed a significant survival benefit for patients who underwent complete resection (223 months) versus those with subtotal resection (138 months, p < 0.05). Factors such as age, sex, the use of up-front radiation, and whether the patient had a recurrence did not show statistical significance related to overall survival or progression free survival. Radiation in the form of external beam radiotherapy given at the time of the first recurrence did trend towards improved progression free survival (56 months) compared to those patients who were not radiated (22 months, p = 0.09) All patients with radical resection went on to never have a recurrence. Our results indicate that HPC are tumors with limited response to radiation and best treated with aggressive resection. Future studies will determine whether molecular-based therapies may provide added adjuvant benefit.     

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 48 h 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 48 h of admission, emphasizing the importance of accurate and early diagnosis of ISA.     

Prognostic factors and treatment options for paediatric ependymomas

The aim of this study was to determine factors of prognostic relevance for paediatric ependymomas, and evaluate the efficacy of treatment modalities. This is a retrospective study of 43 patients with ependymoma (<18 years) who underwent a combination of surgical excision, chemotherapy, and/or radiotherapy treatment at The Prince of Wales Cancer Centre between 1969 and 2009. Statistical analysis was performed to assess the prognostic relevance of various parameters affecting the two-year and five-year overall survival (OS) and progression-free survival (PFS). The five-year OS and PFS were 50.3% and 44.8% respectively (median follow-up 50 months). Eighteen patients (41.9%) experienced tumour recurrence: 13 had a local recurrence (LR) and five had both LR and distant recurrence. On univariate analysis, a more favourable prognosis in terms of both OS and PFS was evident for supratentorial tumours compared to infratentorial tumours (OS p = 0.007, PFS p = 0.045), stereotactic radiosurgery/ fractionated stereotactic radiotherapy compared to craniospinal irradiation or local posterior fossa/local brain ± boost radiotherapy modalities (OS p = 0.047, PFS p = 0.031), total radiotherapy dose >50 Gy compared to ?50 Gy (OS p = 0.008, PFS p = 0.005), and in patients with no tumour recurrence compared to those with recurrence (OS p = 0.03, PFS p < 0.001). Although not statistically significant, a more favourable multivariate outcome was evident in patients who underwent complete surgical resection. Chemotherapy treatment and histopathological grade, however, were not relevant to prognosis. This study supports the need to pursue more aggressive treatment for infratentorial and/or recurrent tumours. Ideal treatment involves maximal surgical resection, followed by adjuvant radiotherapy (>50 Gy).