Surgical treatment of complex spinal cord lipomas

Purpose

This paper shows the long-term benefits of total/near-total resection of complex spinal cord lipomas and meticulous reconstruction of the neural placode, and specifically, its advantage over partial resection, and over non-surgical treatment for the subset of children with asymptomatic virgin lipomas.

Methods

The technique of total resection and placode reconstruction, together with technical nuances, are described in detail. We added 77 patients with complex lipomas to our original lipoma series published in 2009 and 2010, to a total of 315 patients who had had total or near-total resection and followed for a span of 20 years. Long-term outcome is measured by overall progression-free survival (PFS) with the Kaplan–Meier analysis, and by subgroup Cox proportional recurrence hazard analysis for the influence on outcome of 4 predictor variables of lipoma type, presence of symptoms, prior surgery, and post-operative cord–sac ratio. These results are compared to an age-matched, lesion-matched series of 116 patients who underwent partial lipoma resection over 11 years. The results for total resection is also compared to two large published series of asymptomatic lipomas followed without surgery over 9 to 10 years, to determine whether prophylactic total resection confers better long-term protection over conservative treatment for children with asymptomatic lipomas..

Results

The PFS after total resection for all lipoma types and clinical subgroups is 88.1 % over 20 years versus 34.6 % for partial resection at 10.5 years (p?<?0.0001). Culling only the asymptomatic patients with virgin (previously unoperated) lipomas, the PFS for prophylactic total resection for this subgroup rose to 98.8 % over 20 years, versus 67 % at 9 years for one group of non-surgical treatment and 60 % at 10 years for another group of conservative treatment. Our own as well as other published results of partial resection also compare poorly to non-surgical treatment for the subset of asymptomatic virgin lipomas. Multivariate subgroup analyses show that cord–sac ratio is the only independent variable that predicts outcome, with a 96.9 % PFS for ratio <30 % (loosest sac), 86.2 % for ratio between 30 and 50 %, and 78.3 % for ratio >50 % (tightest sac), and a threefold increase in recurrence hazard for high ratios (p?=?0.0009). Pre-operative patient profiling using multiple correspondence analysis shows the ideal patient for total resection is a child less than 2 years old with a virgin asymptomatic lipoma, who, with a PFS of 99.2 %, is virtually cured by total resection.

Conclusion

Total/near-total resection of complex lipomas and complete reconstruction of the neural placode achieves far better long-term protection against symptomatic recurrence than partial resection for all lesions; and for the subset of asymptomatic virgin lipomas, also better than non-surgical treatment. Partial resection in many cases produces worse outcome than conservative treatment for asymptomatic lesions.     

Efficacy of therapeutic play for pediatric brain tumor patients during external beam radiotherapy

Objective

External beam radiotherapy (EBRT) is frequently used to improve disease control for pediatric brain tumor patients. However, to facilitate the radiotherapy (RT) procedure, “forced” type interventions including conscious sedation or general anesthesia are frequently used to manage patients’ fear and anxiety. The aim of this study was to investigate the effects of therapeutic play (TP) in reducing anxiety for pediatric brain tumor patients treated by EBRT.

Methods

Between April 1st and September 30th, 2009, 19 young brain tumor patients, aged 3–15 years and recommended for RT, were recruited: ten to a control group and nine to the study intervention group. The study group was introduced with TP during EBRT. The Beck Youth Anxiety Inventory and the Faces Anxiety Scale were used to evaluate patients’ psychological levels of anxiety. The heart rate variability and salivary cortisol concentrations were used to indicate the patients’ physical levels of anxiety. Both the psychological and physiological tests were administered to all subjects before and after the RT procedure.

Results

The study group had significantly lower anxiety scores and expressed fewer negative emotions than did the control group before EBRT.

Conclusions

TP can not only improve the quality of medical services but can also reduce costs and staffing demands. In addition, it can help lower young patients’ anxiety and fear during medical procedures. As a result, it further decreases the potential negative impacts of hospitalization on these young patients.     

The interface between phonetic and lexical abilities in early Cantonese language development

Data from the Cantonese Communicative Development Inventory (CCDI) is used to review the phonological preferences of younger (16–22 months) and older (23–30 month) groups of children in the lexical items they are reported to be able to say. Analogous results to those found for English emerge from the Cantonese data: the younger group display selectivity in the initial consonants of words they say, and their preferences accord with developmental tendencies in Cantonese phonology. From children whose scores fell below the tenth percentile of the CCDI, a subset were followed up 1 year later and their linguistic progress evaluated. Only a proportion of these children were below still below the tenth percentile for vocabulary at follow‐up. Their lexical immaturities were accompanied by limited phonetic abilities. The implications of the findings are discussed.     

Estrogen‐related receptor β deletion modulates whole‐body energy balance via estrogen‐related receptor γ and attenuates neuropeptide Y gene expression

Estrogen‐related receptors (ERRs) α, β and γ are orphan nuclear hormone receptors with no known ligands. Little is known concerning the role of ERRβ in energy homeostasis, as complete ERRβ‐null mice die mid‐gestation. We generated two viable conditional ERRβ‐null mouse models to address its metabolic function. Whole‐body deletion of ERRβ in Sox2‐Cre:ERRβ^lox/lox mice resulted in major alterations in body composition, metabolic rate, meal patterns and voluntary physical activity levels. Nestin‐Cre:ERRβ^lox/lox mice exhibited decreased expression of ERRβ in hindbrain neurons, the predominant site of expression, decreased neuropeptide Y (NPY) gene expression in the hindbrain, increased lean body mass, insulin sensitivity, increased energy expenditure, decreased satiety and decreased time between meals. In the absence of ERRβ, increased ERRγ signaling decreased satiety and the duration of time between meals, similar to meal patterns observed for both the Sox2‐Cre:ERRβ^lox/lox and Nestin‐Cre:ERRβ^lox/lox strains of mice. Central and/or peripheral ERRγ signaling may modulate these phenotypes by decreasing NPY gene expression. Overall, the relative expression ratio between ERRβ and ERRγ may be important in modulating ingestive behavior, specifically satiety, gene expression, as well as whole‐body energy balance.     

Canonical transient receptor potential channel subtype 3‐mediated hair cell Ca2+ entry regulates sound transduction and auditory neurotransmission

The physiological significance of canonical transient receptor potential (TRPC) ion channels in sensory systems is rapidly emerging. Heterologous expression studies show that TRPC3 is a significant Ca²⁺ entry pathway, with dual activation via G protein‐coupled receptor (GPCR)–phospholipase C–diacylglycerol second messenger signaling, and through negative feedback, whereby a fall in cytosolic Ca²⁺ releases Ca²⁺–calmodulin channel block. We hypothesised that the latter process contributes to cochlear hair cell cytosolic Ca²⁺ homeostasis. Confocal microfluorimetry with the Ca²⁺ indicator Fluo‐4 acetoxymethylester showed that, when cytosolic Ca²⁺ was depleted, Ca²⁺ re‐entry was significantly impaired in mature TRPC3^?/? inner and outer hair cells. The impact of this disrupted Ca²⁺ homeostasis on sound transduction was assessed with the use of distortion product otoacoustic emissions (DPOAEs), which constitute a direct measure of the outer hair cell transduction that underlies hearing sensitivity and frequency selectivity. TRPC3^?/? mice showed significantly stronger DPOAE (2f₁ ? f₂) growth functions than wild‐type (WT) littermates within the frequency range of best hearing acuity. This translated to hyperacusis (decreased threshold) measured by the auditory brainstem response (ABR). TRPC3^?/? and WT mice did not differ in the levels of temporary and permanent threshold shift arising from noise exposure, indicating that potential GPCR signaling via TRPC3 is not pronounced. Overall, these data suggest that the Ca²⁺ set‐point in the hair cell, and hence membrane conductance, is modulated by TRPC3s through their function as a negative feedback‐regulated Ca²⁺ entry pathway. This TPRC3‐regulated Ca²⁺ homeostasis shapes the sound transduction input–output function and auditory neurotransmission.     

Brain imaging research: Does the science serve clinical practice?

Brain imaging represents a potent tool to characterize biomarkers, biological traits that are pathognomonic for specific neurological and neuropsychiatric disorders. Positron emission tomography (PET) and single photon emission computed tomography (SPECT) are imaging techniques used to identify alterations in the density and distribution of neurotransmitters, neuroreceptors, and transporters in specific regions of the brains of people with these disorders. Brain imaging research currently facilitates the elucidation of dysfunction of dopamine, serotonin, acetylcholine, and other substances in people with Alzheimer's and Parkinson's diseases, schizophrenia, alcoholism and other substance abuse disorders, attention deficit/hyperactivity disorder, and the syndromes of restless legs, Lesch-Nyhan, Rett, and Tourette. Thus, brain imaging research offers great potential for the diagnosis, treatment, prevention, and cure of neurological and neuropsychiatric disorders. Brain imaging research also facilitates new drug development and helps establish therapeutic doses of novel drugs. In particular, studies of specific receptors, such as the dopamine D₂ receptor, before and after the administration of doses of drugs that occupy these D₂ receptors, provide the means to determine receptor occupancy. For example, an optimal dose of D₂ antagonist antipsychotics produces occupancy of 65% to 80% of D₂ receptors, while a greater dose carries a risk of extrapyramidal side effects.     

A study of semantic treatment of three Chinese anomic patients

A treatment combining semantic feature analysis and semantic priming was carried out on three Cantonese-speaking brain-injured individuals with word-finding difficulties. Two of the participants with mild to moderate semantic impairment demonstrated significant progress on naming performance. Treatment effects also generalised to semantically related and unrelated untrained items. However, only one of these two participants was able to maintain the treatment gain for at least one month after the therapy was completed. The third patient with severe semantic deficits did not benefit from the intervention. The different outcomes of these participants to the same intervention were explained in terms of the nature of the treatment approach, the patients' underlying language deficits, and their level of cognitive abilities.     

Potassium Depolarization and Raised Calcium Induces α-Synuclein Aggregates

α-Synuclein is the key aggregating protein in Parkinson’s disease (PD), which is characterized by cytoplasmic protein inclusion bodies, termed Lewy bodies, thought to increase longevity of the host neuron by sequestering toxic soluble α-synuclein oligomers. Previous post-mortem studies have shown relative sparing of neurons in PD that are positive for the Ca²⁺ buffering protein, calbindin, and recent cell culture and in vitro studies have shown that α-synuclein aggregation can be induced by Ca²⁺. We hypothesized that depolarization with potassium resulting in raised Ca²⁺ in a PD cell culture model will lead to the formation of α-synuclein protein aggregates and that the intracellular Ca²⁺ buffer, BAPTA-AM, may suppress their formation. Live cell fluorescence microscopy was performed to monitor changes in intracellular free calcium in HEK293T, SH-SY5Y neuroblastoma or stably transfected HEK293T/α-synuclein cells. Raised intracellular free Ca²⁺ was consistently observed in cells treated with KCl, but not controls. Immunohistochemistry analysis on cells 48–72 h after K⁺ treatment revealed two subsets of cells with either large (>2 μm), perinuclear α-synuclein aggregates or multiple smaller (<2 μm), cytoplasmic accumulations. Cells pre-treated with varying concentrations of trimethadione (TMO), a calcium channel blocker, showed suppression of the Ca²⁺ transient following KCl treatment and no α-synuclein aggregates at TMO concentrations >5 μM. Quantitative analysis revealed a significant increase in the number of cells bearing α-synuclein cytoplasmic inclusions in both HEK293T/α-synuclein and SHSY-5Y cells when transient intracellular raised Ca²⁺ was induced (p = 0.001). BAPTA-AM pre-loading significantly suppressed α-synuclein aggregates (p = 0.001) and the intracellular free Ca²⁺ transient. This study indicates that raised intracellular Ca²⁺ mediated by K⁺ depolarization can lead to α-synuclein aggregation.     

Racial and ethnic disparities in the use of antipsychotic medication: a systematic review and meta-analysis

Objective

To conduct a systematic review and meta-analysis of published evidence on ethnic or racial disparities in the outpatient use versus non-use of antipsychotics and in the outpatient use of newer versus older antipsychotics.

Method

Electronic databases were searched for potentially relevant studies. Two independent reviewers conducted the review in three stages: title review, abstract review and full-text review. Included studies were those that: (a) report measures of disparity in the outpatient use of antipsychotic drugs in clearly defined racial or ethnic groups (b) have a primary focus on ethnic or racial disparities, and (c) have adjusted for factors known to influence medicine use. Odds ratios were pooled following the inverse-variance method of weighting effect sizes. I ² statistics were calculated to quantify the amount of variation that is likely due to heterogeneity between studies. Funnel plots were produced and Egger’s statistic was calculated to assess potential publication bias.

Results

No significant differences were found in the odds of using any antipsychotics among African Americans (OR = 1.01, CI = 0.99–1.02) compared with non-African Americans and among Latinos (OR = 0.98, CI = 0.86–1.13) compared with non-Latinos. Small to moderate but statistically non-significant disparities were also noted in other ethnic groups: Asians (OR = 1.10, CI = 0.88–1.36), Maoris (OR = 0.78, CI = 0.53–1.13) and Pacific Islanders (OR = 0.97, CI = 0.84–1.11). Among those who received antipsychotic medication, African Americans (OR = 0.62, CI = 0.50–0.78) and Latinos (OR = 0.77, CI = 0.73–0.81) appeared to have lower odds of receiving newer antipsychotics compared with non-African Americans and non-Latinos.

Conclusion

No significant ethnic disparities in the use versus non-use of any antipsychotics were observed, but, among those who received antipsychotic treatment, ethnic minorities were consistently less likely than non-ethnic minorities to be treated with newer antipsychotics.