Evaluation of bone mineralization in former preterm born children: Phalangeal quantitative ultrasound cannot replace dual-energy X-ray absorptiometry.

BACKGROUND: Preterm infants are at risk of impaired bone health in later life. Dual-energy X-ray absorptiometry-scan (DXA) is the gold standard to determine bone mineralization. Phalangeal quantitative ultrasound (pQUS) is an alternative technique that is inexpensive, easy to use and radiation-free. The aim of this study was to investigate whether both techniques reveal equivalent results. MATERIALS AND METHODS: Sixty former preterm infants (31 boys; 29 girls) received a DXA and pQUS at age 9 to 10 years. DXA measured bone mineral content (BMC) and bone mineral density (BMD) for total body and lumbar spine (L1-4), while pQUS measured the amplitude dependent speed of sound (AD-SoS) and bone transit time (BTT) at metacarpals II-IV providing continuous values and Z-scores based on age and sex. Four statistical methods evaluated the association between both techniques: Pearson's correlation coefficients, partial correlation coefficients adjusted for gestational age, height and BMI, Bland-Altman analysis and cross tabulation. RESULTS: Both techniques showed a statistically significant weak correlation for continuous values as well as Z-scores (0.291-0.462, p < 0.05). Boys had significant and relatively high correlations (0.468-0.585, p < 0.05). In comparison, the correlations for girls were not significant. Correlation coefficients further decreased while calculating the partial correlations. The Bland-Altman plots showed poor agreement. Sensitivity ranged from 33% to 92% and specificity from 16% to 68%. Positive and negative predictive values ranged from 4% to 38% and 82% to 97%, respectively. CONCLUSIONS: We found statistically significant weak correlations and poor agreement between DXA and pQUS measurements. DXA is not equivalent to pQUS and therefore not replaceable by this technique in former preterm born children at the age of 9 to 10 years.

Moderate correlation between systemic IL-6 responses and CRP with trough concentrations of voriconazole.

AIMS: Voriconazole (VCZ) exhibits wide intrapatient pharmacokinetic variability, which is disadvantageous because of its narrow therapeutic range. A considerable part of this variation remains unexplainable, despite extensive knowledge of this drug. It is hypothesized that inflammation has an impact on VCZ pharmacokinetics. In the present study, we investigated the correlation between VCZ trough concentrations and various cytokines. METHODS: A prospective single-centre analysis was performed in adult haematology patients receiving VCZ for possible, probable or proven invasive fungal disease. A linear mixed model was built to explore the contribution of each of the seven pro- and anti-inflammatory cytokines to VCZ trough levels. The Akaike information criterion (AIC) was used to determine the model that fitted the best. RESULTS: Twenty-two patients, with a total of 143 combined samples of VCZ trough levels and cytokines, were included. A significant correlation (P < 0.005) was found between VCZ trough concentrations and interleukin (IL) 6, IL-8 and C-reactive protein (CRP). IL-6 showed the lowest AIC, although differences with the other mediators were marginal. CONCLUSION: VCZ trough concentrations correlate with IL-6, IL-8 and CRP levels but only moderately explain the variability in VCZ pharmacokinetics. Future prospective studies should be undertaken to confirm these findings, and incorporate the data obtained into pharmacokinetic models, to refine the predictive behaviour.

Negative effects of submandibular botulinum neurotoxin A injections on oral motor function in children with drooling due to central nervous system disorders.

AIM: The aims of this study were: (1) to determine the incidence and nature of adverse effects on oral motor function after first injections of botulinum neurotoxin A (BoNT-A) in submandibular glands for excessive drooling in children with central nervous system disorders; and (2) to identify independent predictors of these adverse effects. METHOD: A cohort study involved 209 children (123 males, 86 females, aged 4-27y, median 8y 4mo), who received submandibular BoNT-A injections for drooling. Adverse effects were categorized into swallowing, eating, drinking, articulation, and other problems. Univariable logistic regression was used to study differences in patients with and without adverse effects. Possible predictors were identified using multivariable logistic regression. RESULTS: Transient adverse effects occurred in 33% of the 209 BoNT-A treatments. Almost 80% of these were mild, versus 8.7% severe. Approximately 54% of the adverse effects spontaneously resolved within 4 weeks; 3% still existed after 32 weeks. A diagnosis of cerebral palsy, higher range of BoNT-A dosage, and a pre-treatment drooling quotient <18% were found to be independent predictors of adverse effects. INTERPRETATION: Before using submandibular BoNT-A injections for drooling, potential adverse effects should be discussed. Oral motor function needs to be monitored, because existing dysphagia may be worsened. The identified clinical predictors could be helpful to optimize patient selection.

Potentially inappropriate prescribing in older patients admitted to psychiatric hospital.

OBJECTIVES: The objectives of this study are to determine the prevalence of potentially inappropriate prescribing including potentially inappropriate medications (PIMs) and potential prescription omissions (PPOs) and to assess related risk factors in older people with major psychiatric illness. METHODS: This was a cross-sectional study of older patients hospitalized in a psychiatric hospital (n = 164; mean age 74.9 ± 7.3 years; 62% female). The primary endpoint was the prevalence of participants receiving PIMs and PPOs, which was assessed by using the Beers criteria 2012 and the screening tool of older person's potentially inappropriate prescriptions (STOPP) and screening tool of alert doctors to the right treatment (START) criteria. Univariate and multivariate logistic regression was used to assess significant risk factors for PIMs in this population. RESULTS: A total of 1269 drugs were prescribed to included patients (range: 0-19 drugs/day). PIMs were identified in 47% and 79% of participants, based on the Beers 2012 and STOPP criteria, respectively. Most PIMs (70%) concerned psychotropic drugs. The STOPP criteria identified more PIMs (331) than the Beers criteria 2012 (199). According to the START criteria, 59% of participants had PPOs. The number of prescribed medications was significantly associated with the occurrence of PIMs according to the Beers 2012 [OR 1.2 (95% CI 1.1-1.3)] and STOPP [OR 1.5 (95% CI 1.3-1.8)] criteria. CONCLUSION: Potentially inappropriate prescribing, as identified by the Beers and STOPP/START criteria, is highly prevalent among older patients hospitalized with major psychiatric illness. However, the focus on psychotropic drugs prescription without taking into account the benefit of these drugs to individual patients may limit the application of the Beers and STOPP criteria in psychiatric hospitals.

Prediction of life expectancy in patients with spinal epidural metastasis.

BACKGROUND: The treatment of spinal epidural metastasis is multidisciplinary and usually involves a team of medical oncologists, radiologists, radiotherapists, and spinal surgeons. Life expectancy is one of the factors considered when deciding whether surgery is warranted. Because expert estimates of life expectancy are generally not reliable, a prediction model is needed. Here, we temporally validated a model that was previously validated geographically. METHODS: The records of 110 consecutive patients who were referred with a spinal epidural metastasis were collected prospectively from 2009 to 2013 in order to validate the model, which was published in 2011. The actual and estimated life expectancies were represented graphically, and calibration and discrimination were determined. The calibration slope, Harrell's c-index, D, and R2D were calculated. Hazard ratios in the derivation set of 2011 were compared with the validation set. Misspecification was determined using the joint test for ß*. RESULTS: The calibration slope was 0.64 ± 0.15 (95% CI: 0.34-0.94), Harrell's c-index was 0.72, D was 1.08, and R2D was 0.22, indicating slightly worse discrimination in the derivation set. The joint test for ß* = 0 was statistically significant and indicated misspecification; however, this misspecification was attributed entirely to the surgical group. CONCLUSIONS: We validated a prediction model for surgical decision making, showing that the model's overall performance is good. Based on these results, this model will help clinicians to decide whether to offer surgery to patients with spinal epidural metastasis.

Tetrahydrocannabinol in Behavioral Disturbances in Dementia: A Crossover Randomized Controlled Trial.

OBJECTIVES: Neuropsychiatric symptoms (NPS) are highly prevalent in dementia, but effective pharmacotherapy without important side effects is lacking. This study aims to assess the efficacy and safety of oral tetrahydrocannabinol (THC) in the treatment of NPS in dementia. DESIGN: Randomized, double-blind, placebo-controlled, repeated crossover trial, consisting of six treatment blocks of 2 weeks each. SETTING: Two hospital sites in The Netherlands, September 2011 to December 2013. PARTICIPANTS: Patients with dementia and clinically relevant NPS. INTERVENTION: Within each block THC (0.75 mg twice daily in blocks 1-3 and 1.5 mg twice daily in blocks 4-6) and placebo were administered in random order for 3 consecutive days, followed by a 4-day washout. MEASUREMENTS: Primary outcome was change in Neuropsychiatric Inventory (NPI) score. Analyses were performed intention-to-treat. Data from all subjects were used without imputation. Sample size required for a power of 80% was 20 patients, because of repeated crossover. RESULTS: 22 patients (15 men, mean age 76.4 [5.3] years) were included, of whom 20 (91%) completed the trial. THC did not reduce NPI compared to placebo (blocks 1-3: 1.8, 97.5% CI: -2.1 to 5.8; blocks 4-6: -2.8, 97.5% CI: -7.4 to 1.8). THC was well tolerated, as assessed by adverse event monitoring, vital signs, and mobility. The incidence of adverse events was similar between treatment groups. Four non-related serious adverse events occurred. CONCLUSIONS: This is the largest randomized controlled trial studying the efficacy of THC for NPS, to date. Oral THC did not reduce NPS in dementia, but was well tolerated by these vulnerable patients, supporting future higher dosing studies.

Tetrahydrocannabinol for neuropsychiatric symptoms in dementia: A randomized controlled trial.

OBJECTIVE: To study the efficacy and safety of low-dose oral tetrahydrocannabinol (THC) in the treatment of dementia-related neuropsychiatric symptoms (NPS). METHODS: This is a randomized, double-blind, placebo-controlled study. Patients with dementia and clinically relevant NPS were randomly assigned to receive THC 1.5 mg or matched placebo (1:1) 3 times daily for 3 weeks. Primary outcome was change in Neuropsychiatric Inventory (NPI), assessed at baseline and after 14 and 21 days. Analyses were based on intention-to-treat. RESULTS: Twenty-four patients received THC and 26 received placebo. NPS were reduced during both treatment conditions. The difference in reduction from baseline between THC and placebo was not significant (mean difference NPItotal: 3.2, 95% confidence interval [CI] -3.6 to 10.0), nor were changes in scores for agitation (Cohen-Mansfield Agitation Inventory 4.6, 95% CI -3.0 to 12.2), quality of life (Quality of Life-Alzheimer's Disease -0.5, 95% CI -2.6 to 1.6), or activities of daily living (Barthel Index 0.6, 95% CI -0.8 to 1.9). The number of patients experiencing mild or moderate adverse events was similar (THC, n = 16; placebo, n = 14, p = 0.36). No effects on vital signs, weight, or episodic memory were observed. CONCLUSIONS: Oral THC of 4.5 mg daily showed no benefit in NPS, but was well-tolerated, which adds valuable knowledge to the scarce evidence on THC in dementia. The benign adverse event profile of this dosage allows study of whether higher doses are efficacious and equally well-tolerated. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that for patients with dementia-related NPS, low-dose THC does not significantly reduce NPS at 21 days, though it is well-tolerated.

Taurolidine lock is superior to heparin lock in the prevention of catheter related bloodstream infections and occlusions.

BACKGROUND AND AIMS: Patients on home parenteral nutrition (HPN) are at risk for catheter-related complications; mainly infections and occlusions. We have previously shown in HPN patients presenting with catheter sepsis that catheter locking with taurolidine dramatically reduced re-infections when compared with heparin. Our HPN population therefore switched from heparin to taurolidine in 2008. The aim of the present study was to compare long-term effects of this catheter lock strategy on the occurrence of catheter-related bloodstream infections and occlusions in HPN patients. METHODS: Data of catheter-related complications were retrospectively collected from 212 patients who received HPN between January 2000 and November 2011, comprising 545 and 200 catheters during catheter lock therapy with heparin and taurolidine, respectively. We evaluated catheter-related bloodstream infection and occlusion incidence rates using Poisson-normal regression analysis. Incidence rate ratios were calculated by dividing incidence rates of heparin by those of taurolidine, adjusting for underlying disease, use of anticoagulants or immune suppressives, frequency of HPN/fluid administration, composition of infusion fluids, and duration of HPN/fluid use before catheter creation. RESULTS: Bloodstream infection incidence rates were 1.1/year for heparin and 0.2/year for taurolidine locked catheters. Occlusion incidence rates were 0.2/year for heparin and 0.1/year for taurolidine locked catheters. Adjusted incidence ratios of heparin compared to taurolidine were 5.9 (95% confidence interval, 3.9-8.7) for bloodstream infections and 1.9 (95% confidence interval, 1.1-3.1) for occlusions. CONCLUSIONS: Given that no other procedural changes than the catheter lock strategy were implemented during the observation period, these data strongly suggest that taurolidine decreases catheter-related bloodstream infections and occlusions in HPN patients compared with heparin.

Safety and pharmacokinetics of oral delta-9-tetrahydrocannabinol in healthy older subjects: a randomized controlled trial.

There is a great concern about the safety of THC-based drugs in older people (≥65 years), as most of THC-trials did not include such group. In this phase 1, randomized, double-blind, double-dummy, placebo-controlled, cross-over trial, we evaluated the safety and pharmacokinetics of three oral doses of Namisol(®), a novel THC in tablet form, in older subjects. Twelve healthy older subjects (6 male; mean age 72±5 years) randomly received a single oral dose of 3mg, 5mg, or 6.5mg of THC or matching placebo, in a crossover manner, on each intervention day. The data for 11 subjects were included in the analysis. The data of 1 subject were excluded due to non-compliance to study medication. THC was safe and well tolerated. The most frequently reported adverse events (AEs) were drowsiness (27%) and dry mouth (11%). Subjects reported more AEs with THC 6.5mg than with 3mg (p=0.048), 5mg (p=0.034) and placebo (p=0.013). There was a wide inter-individual variability in plasma concentrations of THC. Subjects for whom the Cmax fell within the sampling period (over 2h), Cmax was 1.42-4.57ng/mL and Tmax was 67-92min. The AUC0-2h (n=11) was 1.67-3.51ng/mL. Overall, the pharmacodynamic effects of THC were smaller than effects previously reported in young adults. In conclusion, THC appeared to be safe and well tolerated by healthy older individuals. Data on safety and effectiveness of THC in frail older persons are urgently required, as this population could benefit from the therapeutic applications of THC.

Self-perception and quality of life in adolescents during treatment for a primary malignant bone tumour.

PURPOSE: Adolescents experience physical and psychosocial changes as part of their normal development. It can be hypothesized that they have lower scores on Quality of Life (QoL) and self-perception when additional changes occur due to cancer treatment. The purpose of our study was to assess self-perception and QoL of adolescents during or up to three months after adjuvant treatment for a primary malignant bone tumour. METHODS: Ten adolescent patients (median age of 15 years) were included. Every patient was matched with two healthy peers. Participants completed the dutch version of the Self Perception Profile of Adolescents (SPPA) to measure self-perception and the KIDSCREEN-52 questionnaire for QoL. For both instruments, normative data were available. RESULTS: Adolescents with a bone tumour had consistently lower scores on QoL as compared to healthy peers. Significantly on domains: physical well-being (P < 0.002), autonomy (P = 0.02), social support (P = 0.04) and school environment (P = 0.02). Scores on self-perception in this group were similar in both the study and control group. CONCLUSIONS: Adolescents with a primary malignant bone tumour during or up to three months after adjuvant treatment had lower scores on QoL (KIDSCREEN-52), significantly on domains of physical well-being and social functioning. Unlike most other quality of life instruments, the KIDSCREEN-52 contains different areas of social functioning and has shown to be a useful instrument in our patient group. Scores on self-perception in this group were similar in both study and control group.

Myocardial 2D strain echocardiography and cardiac biomarkers in children during and shortly after anthracycline therapy for acute lymphoblastic leukaemia (ALL): a prospective study.

AIMS: The aim of this study was to investigate myocardial 2D strain echocardiography and cardiac biomarkers in the assessment of cardiac function in children with acute lymphoblastic leukaemia (ALL) during and shortly after treatment with anthracyclines. METHODS AND RESULTS: Cardiac function of 60 children with ALL was prospectively studied with measurements of cardiac troponin T (cTnT) and N-terminal-pro-brain natriuretic peptide (NT-pro-BNP) and conventional and myocardial 2D strain echocardiography before start (T = 0), after 3 months (T = 1), and after 1 year (T = 2), and were compared with 60 healthy age-matched controls. None of the patients showed clinical signs of cardiac failure or abnormal fractional shortening. Cardiac function decreased significantly during treatment and was significantly decreased compared with normal controls. Cardiac troponin T levels were abnormal in 11% of the patients at T = 1 and were significantly related to increased time to global peak systolic longitudinal strain at T = 2 (P = 0.003). N-terminal-pro-brain natriuretic peptide levels were abnormal in 13% of patients at T = 1 and in 20% at T = 2, absolute values increased throughout treatment in 59%. Predictors for abnormal NT-pro-BNP at T = 2 were abnormal NT-pro-BNP at T = 0 and T = 1, for abnormal myocardial 2D strain parameters at T = 2 cumulative anthracycline dose and z-score of the diastolic left ventricular internal diameter at baseline. CONCLUSION: Children with newly diagnosed ALL showed decline of systolic and diastolic function during treatment with anthracyclines using cardiac biomarkers and myocardial 2D strain echocardiography. N-terminal-pro-brain natriuretic peptide levels were not related to echocardiographic strain parameters and cTnT was not a predictor for abnormal strain at T = 2.Therefore, the combination of cardiac biomarkers and myocardial 2D strain echocardiography is important in the assessment of cardiac function of children with ALL treated with anthracyclines.

Association of disparities in known minor histocompatibility antigens with relapse-free survival and graft-versus-host disease after allogeneic stem cell transplantation.

Allogeneic stem cell transplantation (allo-SCT) can induce remission in patients with hematologic malignancies due to graft-versus-tumor (GVT) responses. This immune-mediated antitumor effect is often accompanied by detrimental graft-versus-host disease (GVHD), however. Both GVT and GVHD are mediated by minor histocompatibility antigen (MiHA)-specific T cells recognizing peptide products from polymorphic genes that differ between recipient and donor. In this study, we evaluated whether mismatches in a panel of 17 MiHAs are associated with clinical outcome after partially T cell-depleted allo-SCT. Comprehensive statistical analysis revealed that DNA mismatches for one or more autosomal-encoded MiHAs was associated with increased relapse-free survival in recipients of sibling transplants (P = .04), particularly in those with multiple myeloma (P = .02). Moreover, mismatches for the ubiquitous Y chromosome-derived MiHAs resulted in a higher incidence of acute GVHD grade III-IV (P = .004), whereas autosomal MiHA mismatches, ubiquitous or restricted to hematopoietic cells, were not associated with severe GVHD. Finally, we found considerable differences among MiHAs in their capability of inducing in vivo T cell responses using dual-color tetramer analysis of peripheral blood samples collected after allo-SCT. Importantly, detection of MiHA-specific T cell responses was associated with improved relapse-free survival in recipients of sibling transplants (P = .01). Our findings provide a rationale for further boosting GVT immunity toward autosomal MiHAs with a hematopoietic restriction to improve outcomes after HLA-matched allo-SCT.

Transition zone prostate cancer: detection and localization with 3-T multiparametric MR imaging.

PURPOSE: To retrospectively compare transition zone (TZ) cancer detection and localization accuracy of 3-T T2-weighted magnetic resonance (MR) imaging with that of multiparametric (MP) MR imaging, with radical prostatectomy specimens as the reference standard. MATERIALS AND METHODS: The informed consent requirement was waived by the institutional review board. Inclusion criteria were radical prostatectomy specimen TZ cancer larger than 0.5 cm(3) and 3-T endorectal presurgery MP MR imaging (T2-weighted imaging, diffusion-weighted [DW] imaging apparent diffusion coefficient [ADC] maps [b < 1000 sec/mm(2)], and dynamic contrast material-enhanced [DCE] MR imaging). From 197 patients with radical prostatectomy specimens, 28 patients with TZ cancer were included. Thirty-five patients without TZ cancer were randomly selected as a control group. Four radiologists randomly scored T2-weighted and DW ADC images, T2-weighted and DCE MR images, and T2-weighted, DW ADC, and DCE MR images. TZ cancer suspicion was rated on a five-point scale in six TZ regions of interest (ROIs). A score of 4-5 was considered a positive finding. A score of 4 or higher for any ROI containing TZ cancer was considered a positive detection result at the patient level. Generalized estimating equations were used to analyze detection and localization accuracy by using ROI-receiver operating characteristics (ROC) curve analyses for the latter. Gleason grade (GG) 4-5 and GG 2-3 cancers were analyzed separately. RESULTS: Detection accuracy did not differ between T2-weighted and MP MR imaging for all TZ cancers (68% vs 66%, P = .85), GG 4-5 TZ cancers (79% vs 72%-75%, P = .13), and GG 2-3 TZ cancers (66% vs 62%-65%, P = .47). MP MR imaging (area under the ROC curve, 0.70-0.77) did not improve T2-weighted imaging localization accuracy (AUC = 0.72) (P > .05). CONCLUSION: Use of 3-T MP MR imaging, consisting of T2-weighted imaging, DW imaging ADC maps (b values, 50, 500, and 800 sec/mm(2)), and DCE MR imaging may not improve TZ cancer detection and localization accuracy compared with T2-weighted imaging. SUPPLEMENTAL MATERIAL: http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.12120281/-/DC1.

Decreased levels of circulating IL17-producing CD161+CCR6+ T cells are associated with graft-versus-host disease after allogeneic stem cell transplantation.

The C-type lectin-like receptor CD161 is a well-established marker for human IL17-producing T cells, which have been implicated to contribute to the development of graft-versus-host disease (GVHD) after allogeneic stem cell transplantation (allo-SCT). In this study, we analyzed CD161(+) T cell recovery, their functional properties and association with GVHD occurrence in allo-SCT recipients. While CD161(+)CD4(+) T cells steadily recovered, CD161(hi)CD8(+) T cell numbers declined during tapering of Cyclosporine A (CsA), which can be explained by their initial growth advantage over CD161(neg/low)CD8(+) T cells due to ABCB1-mediated CsA efflux. Interestingly, occurrence of acute and chronic GVHD was significantly correlated with decreased levels of circulating CD161(+)CD4(+) as well as CD161(hi)CD8(+) T cells. In addition, these subsets from transplanted patients secreted high levels of IFNγ and IL17. Moreover, we found that CCR6 co-expression by CD161(+) T cells mediated specific migration towards CCL20, which was expressed in GVHD biopsies. Finally, we demonstrated that CCR6(+) T cells indeed were present in these CCL20(+) GVHD-affected tissues. In conclusion, we showed that functional CD161(+)CCR6(+) co-expressing T cells disappear from the circulation and home to GVHD-affected tissue sites. These findings support the hypothesis that CCR6(+)CD161-expressing T cells may be involved in the immune pathology of GVHD following their CCL20-dependent recruitment into affected tissues.

Age at diagnosis and breast cancer survival in iran.

Background. Tumour characteristics are the most important prognostic factors in breast cancer. Patient-related factors such as young age at diagnosis, obesity, and smoking behaviour may also modify disease outcome. Due to the absence of a unique definition for "young age breast cancer" and the resulting variation in disease management, findings on the association between young age and prognosis of breast cancer are controversial. Methods. This study included 1500 patients with a primary diagnosis of breast cancer in six Iranian hospitals from 5 provinces. We modelled the relative excess risk (RER) of breast cancer death to age at diagnosis and tumour characteristics. Results. Excess risks of death were observed for stage IV disease and poorly differentiated tumours: RER of 4.3 (95% CI: 1.05-17.65) and 3.4 (95% CI: 1.17-9.87), respectively. "Older" patients, particularly those aged 50 and over, presented more often with advanced and poorly differentiated tumours (P = 0.001). After adjustment for stage, histological grade, Her-2 expression, estrogen and progesterone receptors, and place of residency, breast cancer mortality was not significantly different across age groups. Conclusion. We conclude that there is no prognostic effect of age at diagnosis of breast cancer among breast cancer patients treated at cancer centres in different parts of Iran; young and relatively old women have similar risks of dying from breast cancer.

Mutations in the chromatin modifier gene KANSL1 cause the 17q21.31 microdeletion syndrome.

We show that haploinsufficiency of KANSL1 is sufficient to cause the 17q21.31 microdeletion syndrome, a multisystem disorder characterized by intellectual disability, hypotonia and distinctive facial features. The KANSL1 protein is an evolutionarily conserved regulator of the chromatin modifier KAT8, which influences gene expression through histone H4 lysine 16 (H4K16) acetylation. RNA sequencing studies in cell lines derived from affected individuals and the presence of learning deficits in Drosophila melanogaster mutants suggest a role for KANSL1 in neuronal processes.

Essential features of Chiari II malformation in MR imaging: an interobserver reliability study--part 1.

PURPOSE: Brain MR imaging is essential in the assessment of Chiari II malformation in clinical and research settings concerning spina bifida. However, the interpretation of morphological features of the malformation on MR images may not always be straightforward. In an attempt to select those features that unambiguously characterize the Chiari II malformation, we investigated the interobserver reliability of all its well-known MR features. METHODS: Brain MR images of 79 children [26 presumed to have Chiari II malformation, 36 presumed to have no cerebral abnormalities, and 17 children in whom some Chiari II malformation features might be present; mean age 10.6 (SD 3.2; range, 6-16) years] were blindly and independently reviewed by three observers. They rated 33 morphological features of the Chiari II malformation as present, absent, or indefinable in three planes (sagittal, axial, and coronal). The interobserver reliability was assessed using κ statistics. RESULTS: Twenty-three of the features studied turned out to be unreliable, whereas the interobserver agreement was almost perfect (κ value > 0.8) for nine features (eight in the sagittal plane and one in the axial plane, but none in the coronal plane). CONCLUSIONS: This study presents essential features of the Chiari II malformation on MR images by ruling out the unreliable features. Using these features may improve the assessment of Chiari II malformation in clinical and research settings.

Interobserver reliability and diagnostic performance of Chiari II malformation measures in MR imaging--part 2.

PURPOSE: Brain MR imaging is essential in the assessment of Chiari II malformation in clinical and research settings concerning spina bifida. However, the interpretation of MR images of the malformation is not always straightforward. Morphometric analyses of the extent of Chiari II malformation may improve the assessment. In an attempt to select appropriate morphometric measures for this purpose, we investigated the interobserver reliability and diagnostic performance of several morphometric measures of Chiari II malformation on MR images. METHODS: Brain MR images of 79 children [26 with open spinal dysraphism, 17 with closed spinal dysraphism, and 36 without spinal dysraphism; mean age 10.6 (SD 3.2; range, 6-16) years] were evaluated. All children had been assessed for Chiari II malformation (defined as cerebellar herniation in combination with open spinal dysraphism; n = 23). Three observers blindly and independently reviewed the MR images for 21 measures of the cerebellum, brainstem, and posterior fossa in three planes. The interobserver reliability was assessed by an agreement index (AI = 1 - RRE) and the diagnostic performance by receiver operating characteristic analyses. RESULTS: Reliability was good for most measures, except for the degree of herniation of the vermis and tonsil. Most values differed statistically significantly between children with and without Chiari II malformation. The measures mamillopontine distance and cerebellar width showed excellent diagnostic performance. CONCLUSIONS: Morphometric measures may reliably quantify the morphological distortions of Chiari II malformation on MR images and provide additional tools to assess the severity of Chiari II malformation in clinical and research settings.

Persistent reduction in left ventricular strain using two-dimensional speckle-tracking echocardiography after balloon valvuloplasty in children with congenital valvular aortic stenosis.

BACKGROUND: The aim of this study was to investige serial changes of myocardial deformation using two-dimensional speckle-tracking echocardiographic (2DSTE) imaging in children undergoing balloon valvuloplasty for congenital valvular aortic stenosis (VAS). METHODS: Thirty-seven children with isolated congenital VAS were enrolled in this study prospectively. Patients underwent echocardiographic evaluation at three instances: before balloon valvuloplasty, 6 months after intervention, and 3 years after intervention. Longitudinal, circumferential, and radial peak systolic strain values were determined, as well as systolic strain rate and the time to peak global systolic strain. Linear mixed statistical models were used to assess changes in 2DSTE parameters after balloon intervention. Using one-way analysis of variance, 2DSTE results at 3-year follow-up were compared with 2DSTE measurements in 74 healthy age-matched children and 76 children with uncorrected VAS whose severity of stenosis corresponded to residual stenosis of study subjects at 3-year follow-up. RESULTS: Global peak strain and strain rate measurements in all three directions were decreased before intervention compared with healthy children. Global peak strain and strain rate measurements increased significantly (P < .001) several months after balloon valvuloplasty and continued to increase at 3-year follow-up. However, at 3-year follow-up, global peak strain and strain rate in the longitudinal and circumferential directions were significantly lower (P < .001) compared with both control groups. Measurements of time to peak global systolic strain were significantly shorter at early follow-up compared with measurements before intervention (P < .05). CONCLUSIONS: Shortly after balloon valvuloplasty for severe congenital VAS, there is an improvement in systolic myocardial deformation. However, 2DSTE parameters do not return to normal at 3-year follow-up. These abnormalities in systolic deformation cannot be fully attributed to residual stenosis or aortic regurgitation.