Effect of tranexamic acid on intraoperative blood loss and transfusion requirements in patients undergoing excision of intracranial meningioma

Surgical excision of meningioma is often complicated by significant blood loss requiring blood transfusion with its attendant risks. Although tranexamic acid is used to reduce perioperative blood loss, its blood conservation effect is uncertain in neurosurgery. Sixty adults undergoing elective craniotomy for meningioma excision were randomized to receive either tranexamic acid or placebo, initiated prior to skin incision. Patients in the tranexamic acid group received intravenous bolus of 20 mg/kg over 20 min followed by an infusion of 1 mg/kg/h till the conclusion of surgery. Intraoperative blood loss, transfusion requirements and estimation of surgical hemostasis using a 5-grade scale were noted. Postoperatively, the extent of tumor excision on CT scan and complications were observed. Demographics, tumor characteristics, amount of fluid infusion, and duration of surgery and anesthesia were comparable between the two groups. The amount of blood loss was significantly less in tranexamic acid group compared to placebo (830 ml vs 1124 ml; p = 0.03). The transfusion requirement was less in tranexamic acid group (p > 0.05). The patients in tranexamic acid group fared better on a 5-grade surgical hemostasis scale with more patients showing good hemostasis (p = 0.007). There were no significant differences between the groups with regards to extent of tumor removal, perioperative complications, hospital stay or neurologic outcome. To conclude, administration of tranexamic acid significantly reduced blood loss in patients undergoing excision of meningioma. Fewer patients in the tranexamic acid group received blood transfusions. Surgical field hemostasis was better achieved in patients who received tranexamic acid.     

Reirradiation of recurrent meningioma

Management of meningioma includes observation, resection, and radiation therapy (RT). For patients with recurrent disease, similar options exist. However, the control rate following a second course of RT for recurrent disease is unknown. We reviewed an institutional database of patients with meningioma treated with stereotactic radiosurgery or fractionated stereotactic RT who underwent a second course for recurrent disease. Cox regression model was used for analysis. Variables tested included tumor volume, RT type, tumor grade, age at diagnosis, time to progression, and interval between RT. Eleven of 19 patients (58%) experienced disease progression. Median time to second progression was 10 months. Freedom from progression at one year was lower in patients with grade II or III tumors compared to those with grade 1 or unknown histology (17% compared to 92%, p = 0.0054). Cox regression showed that a grade II–III tumor affects progression-free survival (PFS), with a hazard ratio of 5.37 (p = 0.011). Median time to progression (MTP) for patients with grade II–III tumors was eight months. MTP was not reached for patients with grade 1/unknown tumors. Reirradiation for recurrent meningioma yields modest tumor control rates but for patients with grade II or III tumors, outcomes are poor.     

Early postoperative emergency department presentation predicts poor long-term outcomes in patients surgically treated for meningioma

Previous authors have identified a number of factors that predict morbidity, mortality, and recurrence in patients undergoing resection of a meningioma. We sought to study a novel potential prognostic indicator: early postoperative visit to the emergency department (ED). We conducted a retrospective cohort study on 239 patients who underwent a meningioma resection at our institution between 2001 and 2013 with over 3 months of follow-up postoperatively. All postoperative entries in the medical record were reviewed to identify any ED visit with a neurologic or wound-related complaint within a 90 day postoperative period. The relationships between ED presentation, tumor grade, and extent of surgical resection with future risk of operative recurrence and mortality were analyzed using Fisher’s exact test. Variables associated with increased risks of mortality or operative recurrence in a univariate analysis were then included in the multivariate logistic regression model. Patients with a postoperative ED visit were found to be significantly more likely to die during the follow-up period (23.0% versus 4.85%, p < 0.0001) or develop an eventual operative recurrence (12.2% versus 3.0%, p = 0.0131). Postoperative ED presentation was found to be associated with a higher risk of mortality and operative recurrence independent of pathological tumor grade (p < 0.0001 and p = 0.0102, respectively). Presentation to the ED is associated with significantly higher rates of future operative recurrence and mortality in patients with recent meningioma resections. This poor prognostic relationship is independent of tumor pathological grade. Increased vigilance and follow-up may be warranted in such patients.     

Can we predict intraoperative blood loss in meningioma patients? Application of dynamic susceptibility contrast-enhanced magnetic resonance imaging

PurposeTo evaluate the potential of quantitative dynamic susceptibility contrast (DSC) perfusion MR imaging parameters as imaging biomarkers for predicting intraoperative blood loss in meningioma.MethodsFifty-one non-embolized meningioma patients who had undergone preoperative DSC perfusion MR imaging were retrospectively included. The corrected relative cerebral blood volume (rCBV) and leakage coefficient (K₂) of the entire enhanced tumor were obtained using leakage correction. Tumor volume, location, grade, and other clinical variables, were also analyzed. To investigate the vascularity and vascular permeability of meningiomas, and their correlation with predicting estimated blood loss (EBL) using preoperative DSC perfusion MR imaging, the authors proposed an index reflecting the inherent tendency of meningiomas to bleed after controlling volume (i.e., EBL/cm³). Simple regression was performed to identify predictors of EBL/cm³; subsequently, the relevant variables included in the stepwise multiple linear regression.ResultsOn univariate analysis, EBL/cm³ was correlated with rCBV (r = 0.677; P < 0.001), K₂ (r = 0.294; P = 0.036), and tumor volume (r = –0.312, P = 0.026). EBL/cm³ was not correlated with age (P = 0.873), sex (P = 0.404), tumor location (P = 0.327), or histological grade (P = 0.230). On multiple linear regression, rCBV (β = 0.663 [0.463–0.864], B = 1.293 [0.903–1.684; P < 0.001) and K₂ (β = 0.260 [0.060–0.460], B = 2.277 [0.523–4.031], P = 0.012), were the only independent predictors of EBL/cm³.ConclusionThe rCBV and K₂ derived from DSC perfusion MR imaging in meningiomas may serve as feasible tools for clinicians to predict intraoperative blood loss and facilitate surgical planning.     

Pleomorphic xanthoastrocytomas: Institutional experience of 18 patients

Pleomorphic xanthoastrocytoma (PXA) is a rare, low-grade glioma (World Health Organization Grade II) that most often presents in the first two decades of life. We summarize and present our institutional experience in the management of these tumors. All patients managed for PXA at the University of California San Francisco were retrospectively identified through chart review. Patient demographics, tumor characteristics, management, and follow-up were extracted using medical records. Primary endpoints were overall (OS) and progression-free survival (PFS). In total, nineteen patients were treated for PXA from 1993–2011. Clinical data were available for analysis in 18 patients. Median OS was 209.0 months after date of surgery, with both 5 year and 10 year survival rates of 94%. In this patient cohort, tumor grade (p = 0.07), age (p = 0.32), and extent of resection (p = 0.58) did not predict OS. The majority of tumors (78%) recurred. Median PFS was 21.7 months, with 5 year and 10 year recurrence-free rates of 28% and 22%. On univariate analysis, tumor grade (p = 0.01), but not age (p = 0.51), size (p = 0.30), or extent of resection (p = 0.21), was the only covariate predictive of PFS. In patients presenting with higher tumor grade, however, earlier recurrence was demonstrated. Furthermore, the majority of recurrences (36%) occurred within the first 6 months post-operatively, which indicates the need to closely follow patients for that time.     

Outcome of resection of WHO Grade II meningioma and correlation of pathological and radiological predictive factors for recurrence

This study investigated whether extent of surgical resection (Simpson and Shinshu grade) along with pathological and radiological factors influence the tumor control and recurrence-free survival (RFS) of patients with World Health Organization (WHO) grade II meningiomas. The clinical, radiological and surgical notes on the 59 patients with WHO grade II meningioma managed at our institution over 20 years were retrospectively reviewed. In this study, median survival time was 41 months. The overall recurrence rate in Simpson grades I and II resection was 31%. In grades III and IV, the overall recurrence rate was 73%, and this high recurrence rate in these groups was confined within 5 years. In Cox regression analysis, combined data of grades (I and II)/complete resection showed a significant difference in RFS compared to grades (III and IV)/subtotal resection (p = 0.0001). A similar trend of RFS (p = 0.0001) was observed with the Shinshu grading system of resection. In addition, a Ki-67% marker for proliferation less than 15% (p = 0.029), absence of certain radiological features including heterogeneous enhancement, cyst formation and peritumoral edema (p = 0.006), and repeat surgery for recurrent meningioma was associated with better survival (p = 0.014). However, radiosurgery did not have a beneficial role in the treatment of recurrence of atypical meningioma. The Simpson grading system is the primary predictor of recurrence of WHO grade II meningioma after resection. In addition, certain pathological and radiological features need to be considered as possible factors of recurrence after resection. Lastly, depending on the likely risks and surgical morbidity, repeat surgical resection should be performed for recurrent atypical meningioma.     

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.     

Grading meningiomas utilizing multiparametric MRI with inclusion of susceptibility weighted imaging and quantitative susceptibility mapping

Background and purposeThe ability to predict high-grade meningioma preoperatively is important for clinical surgical planning. The purpose of this study is to evaluate the performance of comprehensive multiparametric MRI, including susceptibility weighted imaging (SWI) and quantitative susceptibility mapping (QSM) in predicting high-grade meningioma both qualitatively and quantitatively.MethodsNinety-two low-grade and 37 higher grade meningiomas in 129 patients were included in this study. Morphological characteristics, quantitative histogram analysis of QSM and ADC images, and tumor size were evaluated to predict high-grade meningioma using univariate and multivariate analyses. Receiver operating characteristic (ROC) analyses were performed on the morphological characteristics. Associations between Ki-67 proliferative index (PI) and quantitative parameters were calculated using Pearson correlation analyses.ResultsFor predicting high-grade meningiomas, the best predictive model in multivariate logistic regression analyses included calcification (β = 0.874, P = 0.110), peritumoral edema (β = 0.554, P = 0.042), tumor border (β = 0.862, P = 0.024), tumor location (β = 0.545, P = 0.039) for morphological characteristics, and tumor size (β = 4 × 10⁻⁵, P = 0.004), QSM kurtosis (β = − 5 × 10⁻³, P = 0.058), QSM entropy (β = − 0.067, P = 0.054), maximum ADC (β = − 1.6 × 10⁻³, P = 0.003), ADC kurtosis (β = − 0.013, P = 0.014) for quantitative characteristics. ROC analyses on morphological characteristics resulted in an area under the curve (AUC) of 0.71 (0.61–0.81) for a combination of them. There were significant correlations between Ki-67 PI and mean ADC (r = − 0.277, P = 0.031), 25^th percentile of ADC (r = − 0.275, P = 0.032), and 50^th percentile of ADC (r = − 0.268, P = 0.037).ConclusionsAlthough SWI and QSM did not improve differentiation between low and high-grade meningiomas, combining morphological characteristics and quantitative metrics can help predict high-grade meningioma.     

Enteral nutrition feeding alters antioxidant activity in unstimulated whole saliva composition of patients with neurological disorders

Patients with neurological disorders have an increased risk of oral and systemic diseases due to compromised oral hygiene. If patients lose the ability to swallow and chew food as a result of their disorder, enteral nutrition is often utilized. However, this type of feeding may modify salivary antioxidant defenses, resulting in increased oxidative damage and the emergence of various diseases. The aim of this study was to evaluate the effects of enteral nutrition on biochemical parameters in the unstimulated whole saliva composition of patients with neurological disorders. For this, enzymatic (superoxide dismutase – SOD; glutathione peroxidase – GPx) and non-enzymatic (uric acid; ferric ion reducing antioxidant power – FRAP) antioxidant activity, as well as a marker for oxidative damage (thiobarbituric acid reactive substances – TBARS) were analyzed. Unstimulated whole saliva was collected from 12 patients with neurological disorders and tube-feeding (tube-fed group – TFG), 15 patients with neurological disorders and normal feeding via the mouth (non-tube-fed group – NTFG), and 12 volunteers without neurological disorders (control group – CG). The daily oral hygiene procedures of TFG and NTFG patients were similar and dental care was provided monthly by the same institution's dentist. All patients exhibited adequate oral health conditions. The salivary levels of FRAP, uric acid, SOD, GPx, TBARS, and total protein were compared between studied groups. FRAP was increased (p < 0.05) in the NTFG (4651 ± 192.5 mmol/mL) and the TFG (4743 ± 116.7 mmol/mL) when compared with the CG (1844 ± 343.8 mmol/mL). GPx values were lower (p < 0.05) in the NTGF (8.24 ± 1.09 mmol/min/mg) and the TFG (8.37 ± 1.60 mmol/min/mg) than in the CG (15.30 ± 2.61 mmol/min/mg). Uric acid in the TFG (1.57 ± 0.23 mg/dL) was significantly lower than in the NTFG (2.34 ± 0.20 mg/dL) and the CG (3.49 ± 0.21 mg/dL). Protein was significantly lower in the TFG (5.35 ± 0.27 g/dL) than in the NTFG (7.22 ± 0.57 g/dL) and the CG (7.86 ± 0.54 g/dL). There was no difference in the salivary flow rate and SOD between groups. Enteral nutrition in patients with neurological disorders was associated with lower oxidative damage, resulting in increased salivary antioxidant capacity. These results emphasize the importance of oral care for this population to prevent oral and systemic diseases.     

Physical fitness assessment in multiple sclerosis patients: A controlled study

There is growing evidence to show the effectiveness of physical exercise for multiple sclerosis (MS) patients. Aim of this study was to evaluate aerobic capacity, strength, balance, and the rate of perceived exertion (RPE) after exercise, in ambulatory patients with mild MS and matched control healthy participants. Seventeen MS patients aged 48.09 ± 10.0 years, with mild MS disability (Expanded Disability Status Scale: EDSS 1.5 to 4.5) and 10 healthy sedentary age matched (41.9 ± 11.2 years) subjects volunteered for the study. MS patients underwent medical examination with resting electrocardiogram, arterial blood pressure, EDSS, and Modified Fatigue Impact Scale-MFIS. Both groups also underwent physical assessment with the Berg Balance Scale^, test (Berg), Six Minutes Walking Test (6MWT), maximal isometric voluntary contraction (MIVC) of forearm, lower limb, shoulder strength test, and the Borg 10-point scale test. The one-way ANOVA showed significant differences for MFIS (F_1.19 = 9.420; p < 0.01), Berg (F_1.19 = 13.125; p < 0.01), handgrip MIVC (F_1.19 = 4.567; p < 0.05), lower limbs MIVC (F_1.19 = 7.429; p < 0.01), and 6MWT (F_1.19 = 28.061; p < 0.01) between groups. EDSS, Berg test and Borg scores explained 80% of 6MWT variation. Mild grade EDSS patients exhibited impaired balance, muscle strength, and low self pace-6MWT scores, whereas RPE response after the exercise was similar to that of sedentary individuals. Both groups showed similar global physiological adjustments to exercise.     

Prognostic impact of sleep duration and sleep efficiency on mortality in patients with chronic heart failure

BackgroundBoth short and long self-reported sleep duration (SD_SR) has been linked to increased mortality. Our analysis tested the hypothesis that long SD_SR is paralleled by impaired objective sleep efficiency (SE_PSG) measured by polysomnography (PSG) and that impaired SE_PSG is a risk factor for death in patients with chronic heart failure (CHF).MethodsSD_SR and SE_PSG were assessed by standardized questionnaire and PSG in 188 consecutive CHF patients (age range, 63 ± 10 year; left ventricular ejection fraction, 34 ± 10%) admitted to the Sleep Center of the University Hospital Regensburg between 1/2002 and 12/2009. The mean follow-up period was 44 ± 26 months.ResultsSE_PSG in CHF patients from the highest quintile of SD_SR (⩾9 h) was significantly lower compared with the middle quintile (7.25–8 h; 71 ± 15% vs 77% ± 11%; p = 0.032) and similar to the lowest quintile (⩽5.75 h; 71 ± 15% vs 71 ± 16%, p = 0.950). SE_PSG is an independent predictor for death in the multivariable model after accounting for the significant confounders age, left ventricular ejection fraction, cause of CHF, and NYHA class (hazard ratio [HR] per 5% increase, 0.85; 95% confidence interval [CI], 0.77–0.93; p < 0.001).ConclusionsData indicate that subjective long sleepers with CHF have poor sleep efficiency. Objectively measured SE_PSG strongly predicts mortality in CHF patients, underscoring the importance of objective assessment of sleep.     

Prevalence of residual excessive sleepiness during effective oral appliance therapy for sleep-disordered breathing

BackgroundOral appliance therapy with a mandibular advancement device (OA_m) can yield to complete therapeutic response (apnea–hypopnea index [AHI] < 5 events/h), though some patients show little or no improvement in daytime sleepiness. The prevalence of residual excessive sleepiness (RES) despite effective treatment with OA_m therapy is unknown. We aimed to determine the prevalence of RES in patients treated with a titratable custom-made duobloc OA_m.MethodsA prevalence study was performed, collecting data from 185 patients with an established diagnosis of sleep-disordered breathing (SDB) under OA_m therapy with a titratable custom-made duobloc device (baseline data were male:female ratio, 129:56; age, 48 ± 9 years; body mass index [BMI], 27 ± 4 kg/m²; Epworth Sleepiness Scale [ESS] score, 10 ± 5; and AHI, 19 ± 12 events/h). A full-night polysomnography was performed at baseline and after 3 months of OA_m therapy. Daytime sleepiness was assessed using the ESS with RES defined as an ESS score of 11 or higher out of 24, despite complete therapeutic response.ResultsOut of 185 patients, 84 patients (45%) showed a complete therapeutic response with an AHI of <5 events per hour after 3 months of OA_m therapy. Despite this normalization of AHI, 27 out of these 84 patients (32%) showed RES and had a significantly higher baseline ESS (15 ± 4 vs 9 ± 4; P < .001) and were younger (43 ± 9 vs 47 ± 9; P = .028) compared to patients without RES.ConclusionRES under OA_m therapy showed a prevalence of up to 32% in SDB patients effectively treated with respect to AHI. Patients with RES were younger and had higher baseline daytime sleepiness.     

Performance status during and after radiotherapy plus concomitant and adjuvant temozolomide in elderly patients with glioblastoma multiforme

For elderly patients with glioblastoma multiforme (GBM), radiotherapy plus concomitant and adjuvant temozolomide has resulted in longer survival. We investigated patient performance status, treatment-related toxicity and overall survival (OS) following treatment. Twenty patients aged 70 years or older with a newly diagnosed GBM were treated with radiotherapy (60 Gy in 16 patients and 40 Gy in four patients) plus concomitant and adjuvant temozolomide. We assessed age, the extent of tumor removal, and initial performance status as possible prognostic factors for OS and good performance status following treatment. The median OS was 11.8 months (95% confidence interval [CI], 8.7–14.8). The median time for patients to reach an Eastern Cooperative Oncology Group (ECOG) performance status grade 2 was 3.0 months (95% CI, 2.4–3.5), and the time to ECOG performance status grade 3 was 5.8 months (95% CI, 1.6–9.9). World Health Organization grade III or grade IV toxicity was observed in four patients (20%), leucopenia and thrombocytopenia was noted in two patients, and major infection occurred in two patients. Univariate analysis showed a significantly longer OS (p = 0.003) and a longer time with good performance status for gross total removal (GTR) (p = 0.003). An initial good performance status was related to a good performance status during and after treatment (p = 0.003). Based on multivariate analysis, GTR was significantly associated with a longer OS (hazard ratio [HR] = 0.236; 95% CI, 0.060–0.922, p = 0.038) and a good performance status (HR = 0.124; 95% CI, 0.022–0.693, p = 0.017). During and after treatment, elderly patients with GBM frequently exhibited an early deterioration of performance status. Therefore, in light of a rapidly fatal illness, elderly patients should be treated to preserve and respect their quality of life.     

Effects of persistent Mal de debarquement syndrome on balance,psychological traits,and motor cortex exctiability

Mal de debarquement syndrome (MdDS) is a poorly characterized and understood disorder of perceived motion. We sought to characterize postural control and the psychological impact of MdDS. Additionally, we explored whether patients with MdDS exhibit altered corticospinal and intracortical excitability. In a case-control study we compared patients with MdDS to age- and sex-matched controls (n = 8/group). Postural stability (σ_r) was quantified from plane phase plots based on center or pressure, and psychological indices of depression, fatigue and kinesiophobia were obtained. Transcranial magnetic stimulation (TMS) was used to assess corticospinal excitability by quantifying the motor evoked potential (MEP) amplitude of the flexor carpi radialis, and intracortical excitability was assessed by quantifying indices of intracortical facilitation (ICF), and short-interval and long-interval intracortical inhibition using a paired-pulse TMS paradigm. The patients with MdDS exhibited greater mean (±standard error of the mean) σ_r during semi-tandem stance (10.9 ± 1.5 compared to 7.1 ± 0.7, p = 0.04), higher levels of kinesiophobia (41.6 ± 2.8 compared to 27.3 ± 2.2), and higher levels of fatigue (27.0 ± 4.1 compared to 48.4 ± 1.0). Patients with MdDS exhibited a higher mean motor threshold (MT) (58.1 ± 2.5 compared to 47.4 ± 2.7% of stimulator output), and larger MEP (13.1 ± 3.1 compared to 5.1 ± 1.2% of maximal compound muscle action potential) but there was no difference in measures of intracortical excitability. These findings suggest that patients with MdDS exhibit impaired postural stability, and high levels of kinesiophobia and fatigue. Additionally, we observed that patients with MdDS exhibit higher MT and large MEP amplitudes, but do not exhibit differences in measures of intracortical excitability, compared to controls. These findings help characterize MdDS, and provide insight into the physiology of MdDS.     

Outcomes and cost-effectiveness of gamma knife radiosurgery and whole brain radiotherapy for multiple metastatic brain tumors

We aimed to analyze the outcomes and cost-effectiveness of gamma knife radiosurgery (GKRS) and whole brain radiotherapy (WBRT) for multiple metastatic brain tumors. Over a period of 5 years, 156 patients with multiple metastatic brain tumors were enrolled and freely assigned by the referring doctors to either gamma knife radiosurgery (GKRS, Group A, n = 56), or to whole brain radiotherapy (WBRT, Group B, n = 100). The follow-up time was set at 1200 days (3.3 years) post-treatment. The number of tumors, patient age, extent of systemic disease and Karnofsky performance scale (KPS) score, were recorded and recursive partitioning analysis used. The outcomes analyzed were: mortality, survival time, neurological complications, post-treatment KPS score, quality-adjusted life years (QALY), and cost-effectiveness. A paired t-test was used for statistical analysis. Mortality rates for patients receiving GKRS and WBRT were 81.1% and 93.0%, respectively (p = 0.05). The mortality rate was lower for GKRS (74.4%) than for WBRT (97.1%) in patients with initial KPS ? 70 (p = 0.02). The mortality rate was also significantly lower for GKRS (78.9%) than WBRT (95.5%) in patients with 2–5 tumors (p < 0.05). Post-treatment KPS score (mean ± standard deviation [s.d.] was higher for patients receiving GKRS (73.8 ± 13.2) than for those receiving WBRT (45.5 ± 26.0), p < 0.01. The median survival time for GKRS and WBRT was 9.5 months and 8.3 months, respectively, p = 0.72. The mean (± s.d.) QALY was 0.76 ± 0.23 for GKRS and 0.59 ± 0.18 for WBRT, respectively (p < 0.05). The cost-effectiveness per unit of QALY was better for the GKRS treatment (US$10,381/QALY) than in the WBRT treatment (US$17,622/QALY), p < 0.05. The cost-effectiveness per KPS score was also higher for the GKRS treatment (US$139/KPS score) than for WBRT (US$229/KPS score), p < 0.01. Thus, the mortality rate for multiple metastatic brain tumors treated by GKRS is significantly better with a good initial KPS score and when the tumor number is 2–5. GKRS results in a better post-treatment KPS score, QALY, and higher cost-effectiveness than WBRT for treating multiple metastatic brain tumors.     

Microvessel density and vascular endothelial growth factor expression as predictors of childrens’ survival from cerebellar medulloblastoma

Cerebellar medulloblastoma is the most common malignant brain tumor of childhood. This neoplasm is highly vascular and has a high growth rate. We aimed to determine whether high microvessel density (MVD) and expression of vascular endothelial growth factor (VEGF) in medulloblastoma tissue is correlated with survival time in children with this tumor. Tissue from 32 cerebellar medulloblastomas in 14 girls and 18 boys was studied. The standard-risk group comprised patients older than 3 years, without metastases of medulloblastoma and a residual post-operative tumor with a surface area less than 1.5 cm². The patients assigned to a high-risk group had at least one of the following indicators: younger than 3 years, metastases, or a residual post-operative tumor with a surface area larger than 1.5 cm². For each tumor, MVD was determined and the expression of VEGF was assessed using immunohistochemical techniques. The 5-year survival rate for the 32 patients was 56.2%. Five-year survival rates were 70.6% and 40.0% for patients in the standard-risk and high-risk groups, respectively. The mean (±standard deviation, SD) MVD for all patients was 22.0 ± 9.1 microvessels per 0.7 mm². There was no difference in the survival rate between the groups with above-average MVD and below-average MVD (66.7% and 50.0%, respectively). Testing revealed 7 tumors with VEGF expression and 25 without. The 5-year survival rates for these 2 groups were not significantly different (57.1% vs. 56.0%, respectively). The mean (±SD) MVD values for the VEGF-positive and VEGF-negative groups were not significantly different (19.1 ± 6.5 vs. 22.9 ± 9.7 microvessels per 0.7 mm², respectively, Mann–Whitney U-test = 78.5, Z = ?0.41, p = 0.68). There were no significant correlations between risk groups and expression of VEGF or MVD. These results indicate that neither high MVD nor the expression of VEGF in tumor tissue predicts poor prognosis in children with cerebellar medulloblastoma.     

Serum nitrite and nitrate levels in children with obstructive sleep-disordered breathing

BackgroundDiminished nitric oxide (NO) levels have been reported in adults with obstructive sleep apnea but no data are available for children with obstructive sleep-disordered breathing (SDB).ObjectivesTo assess levels of serum NO metabolites in children with SDB and to explore the effects of NO metabolites, SDB and their interaction on blood pressure.MethodsMorning nitrite, the sum of nitrite and nitrate (NO_x), and the average of evening and morning blood pressure were assessed in children with SDB referred for polysomnography and in controls without SDB.ResultsForty-three children with SDB (age: 5.8 ± 2.1 years) had moderate-to-severe nocturnal hypoxemia (SpO₂ nadir: 85.6 ± 4%), 54 subjects (6.6 ± 2.7 years) had mild hypoxemia (SpO₂ nadir: 91.4 ± 1.3%) and 20 subjects were controls free of SDB (6.7 ± 3.7 years). Subjects with moderate-to-severe hypoxemia had significantly lower ln-transformed NO metabolites (1.4 ± 0.7, nitrites; 2.6 ± 0.5, NO_x) compared to those with mild hypoxemia (1.9 ± 0.8, nitrites; 3 ± 0.6, NO_x) and controls (2.2 ± 0.7, nitrite; 3 ± 0.6, NO_x; p < 0.05). The effects of NO metabolites and SDB or their interaction on blood pressure were not significant (p > 0.05).ConclusionsModerate-to-severe hypoxemia accompanying SDB is associated with reduced concentrations of morning serum NO metabolites, but NO levels do not seem to affect blood pressure.     

Prevalence of family history in patients with reflex syncope

Reflex syncope is defined by a rapid transient loss of consciousness caused by global cerebral hypoperfusion resulting from vasodilatation and/or bradycardia attributable to inappropriate cardiovascular reflexes. A hereditary component has been suggested, but prevalence of family history may differ among subtypes of reflex syncope, as these have different autonomic responses and pathogeneses may be diverse. The present study aimed to assess the prevalence of a positive family history of syncope and cardiovascular characteristics in patients with cardioinhibitory and vasodepressor reflex syncope. Patients (n = 74) were classified into subtypes of reflex syncope – cardioinhibition/asystole (Vasovagal Syncope International Study subtypes II-B [VASIS II-B], n = 38) or vasodepressor (VASIS III, n = 36) – using the head-up tilt test. Family history was obtained by questionnaires supplemented by interview. Patients with cardioinhibitory syncope had a mean onset of disease 8 years earlier than vasodepressor patients (mean ± standard deviation 14.5 years ± 12.6 for cardioinhibitory patients compared to 22.4 years ± 11.9 for vasodepressor patients, p < 0.001). Thirty-seven (50%) of 74 probands had a positive family history with at least one relative affected with syncope, arrhythmias, known sudden unexpected death, and/or heart disease. The prevalence of a positive family history was higher in patients with cardioinhibitory syncope compared to vasodepressor syncope (24 (63%) compared to 13 (36%); p = 0.02). Overall, 40 first-degree relatives (26%) and 27 second- or third-degree relatives (25%) were affected. The most frequent events in families of patients with cardioinhibitory or vasodepressor reflex syncope were severe syncope and/or arrhythmias, known sudden unexpected deaths, and heart disease. In conclusion, prevalence of familial occurrence of syncope is in agreement with previous studies. However, a high occurrence of all-cardiovascular disorders in cardioinhibitory patients may reflect shared genetic susceptibility to these diseases.     

Clinicopathologic analysis of rhabdoid meningioma

Rhabdoid meningioma is an uncommon variant of meningioma, and was classified separately for the first time in the 2000 World Health Organization’s classification of tumors of the nervous system. Because it often shows malignant histological features and follows an aggressive clinical course, it has been classified as a grade III neoplasm. We describe the clinicopathologic features of 13 patients with this rare tumor. From 13 patients (seven male, six female), 19 specimens of rhabdoid meningioma were obtained between 2001 and 2009. The mean age of patients was 50.4 years at their first operation. The mean postoperative follow-up period was 35.7 months. Five patients experienced tumor recurrence, and two patients died from the disease. The mean time to first recurrence was 36.1 months. The recurrence-free survival rates at 1 and 5 years were 62% and 23%, respectively. Immunohistochemically, all tumors were positive for vimentin and epithelial membrane antigen. MIB-1 labeling indices were higher following tumor recurrence. Close follow-up and aggressive treatment of these tumors is warranted.     

Trilevel adaptive servoventilation for the treatment of central and mixed sleep apnea in chronic heart failure patients

BackgroundSleep-disordered breathing (SDB) in patients with heart failure (HF) is of major prognostic impact, though treatment of simultaneously occurring central and mixed apnea events is challenging. The objective was to examine long-term effects of a new trilevel adaptive servoventilation (ASV) therapy in patients with systolic or diastolic HF.MethodsA total of 45 consecutive patients with a history of HF, elevated N-terminal prohormone of brain natriuretic peptide levels, objective signs of cardiac dysfunction, and moderate to severe SDB (apnea-hypopnea index [AHI] ⩾15/h) with combined central and mixed respiratory events were included in this study and ASV therapy (SOMNOvent CR, Weinmann) was offered.ResultsIn 38 patients (84%), ASV therapy was successfully initiated, with 23 (51%) patients showing appropriate compliance (device use ⩾4 h/night for ⩾5 d/w) after 3.6 ± 1.2 months. In these patients ASV therapy and HF status were re-evaluated. A sustained reduction was achieved in AHI (42.8 ± 17.5/h vs 8.9 ± 5.8/h; p < 0.001) and oxygen saturation. Improvements also were recorded in New York Heart Association (NYHA) functional class (2.4 ± 0.5–1.9 ± 0.4; p < 0.001) and oxygen uptake during cardiopulmonary exercise testing (VO₂ peak, 13.64 ± 3.5–15.8 ± 5.8 ml/kg/min; p < 0.002).ConclusionIn selected HF patients, trilevel ASV therapy is able to treat SDB with combined central and mixed respiratory events. This treatment is associated with an improvement in HF symptoms and objective cardiopulmonary performance.