Objective To examine the ability of magnetic resonance imaging (MRI) patterns of neonatal brain injury defined by the National Institute of Child Health and Human Development Neonatal Research ...Network to predict death or IQ at 6-7 years of age following hypothermia for neonatal encephalopathy. Study design Out of 208 participants, 124 had MRI and primary outcome (death or IQ <70) data. The relationship between injury pattern and outcome was assessed. Results Death or IQ <70 occurred in 4 of 50 (8%) of children with pattern 0 (normal MRI), 1 of 6 (17%) with 1A (minimal cerebral lesions), 1 of 4 (25%) with 1B (extensive cerebral lesions), 3 of 8 (38%) with 2A (basal ganglia thalamic, anterior or posterior limb of internal capsule, or watershed infarction), 32 of 49 (65%) with 2B (2A with cerebral lesions), and 7 of 7 (100%) with pattern 3 (hemispheric devastation), P < .001; this association was also seen within hypothermia and control subgroups. IQ was 90 ± 13 among the 46 children with a normal MRI and 69 ± 25 among the 50 children with an abnormal MRI. In childhood, for a normal outcome, a normal neonatal MRI had a sensitivity of 61%, specificity of 92%, a positive predictive value of 92%, and a negative predictive value of 59%; for death or IQ <70, the 2B and 3 pattern combined had a sensitivity of 81%, specificity of 78%, positive predictive value of 70%, and a negative predictive value of 87%. Conclusions The Neonatal Research Network MRI pattern of neonatal brain injury is a biomarker of neurodevelopmental outcome at 6-7 years of age. Trial registration ClinicalTrials.gov : NCT00005772.
Summary Background We hypothesised that vertebroplasty provides effective analgesia for patients with poorly controlled pain and osteoporotic spinal fractures of less than 6 weeks' duration. The ...effectiveness of vertebroplasty, using an adequate vertebral fill technique, in fractures of less than 6 weeks' duration has not been specifically assessed by previously published masked trials. Methods This was a multicentre, randomised, double-blind, placebo-controlled trial of vertebroplasty in four hospitals in Sydney, Australia. We recruited patients with one or two osteoporotic vertebral fractures of less than 6 weeks' duration and Numeric Rated Scale (NRS) back pain greater than or equal to 7 out of 10. We used an automated telephone randomisation service provided by the National Health and Medical Research Council to assign patients (1:1; stratified according to age, degree of vertebral compression, trauma, corticosteroid use, and hospital) to either vertebroplasty or placebo, immediately before the procedure. Patients received conscious sedation. Vertebroplasty was done with the adequate vertebral fill technique and the placebo procedure with simulated vertebroplasty. Follow-up was for 6 months. Outcome assessors and patients were masked to treatment allocation. The primary outcome was the proportion of patients with NRS pain below 4 out of 10 at 14 days post-intervention in the intention-to-treat population. This study is registered with ClinicalTrials.gov , number NCT01482793. Findings Between Nov 4, 2011, and Dec 5, 2014, 120 patients were enrolled. 61 patients were randomly assigned to vertebroplasty and 59 to placebo. 24 (44%) patients in the vertebroplasty group and 12 (21%) in the control group had an NRS pain score below 4 out of 10 at 14 days (between-group difference 23 percentage points, 95% CI 6–39; p=0·011). Three patients in each group died from causes judged unrelated to the procedure. There were two serious adverse events in each group, related to the procedure (vertebroplasty group) and the fracture (control group). Interpretation Vertebroplasty is superior to placebo intervention for pain reduction in patients with acute osteoporotic spinal fractures of less than 6 weeks' in duration. These findings will allow patients with acute painful fractures to have an additional means of pain management that is known to be effective. Funding Education grant from CareFusion Corporation.
Objective To compare cerebral perfusion and diffusion in survivors of childhood posterior fossa brain tumor with neurologically normal controls and correlate differences with cognitive dysfunction. ...Study design We analyzed retrospectively arterial spin-labeled cerebral blood flow (CBF) and apparent diffusion coefficient (ADC) in 21 patients with medulloblastoma (MB), 18 patients with pilocytic astrocytoma (PA), and 64 neurologically normal children. We generated ANCOVA models to evaluate treatment effects on the cerebral cortex, thalamus, caudate, putamen, globus pallidus, hippocampus, amygdala, nucleus accumbens, and cerebral white matter at time points an average of 5.7 years after original diagnosis. A retrospective review of patient charts identified 12 patients with neurocognitive data and in whom the relationship between IQ and magnetic resonance imaging variables was assessed for each brain structure. Results Patients with MB (all treated with surgery, chemotherapy, and radiation) had significantly lower global CBF relative to controls (10%-23% lower, varying by anatomic region, all adjusted P < .05), whereas patients with PA (all treated with surgery alone) had normal CBF. ADC was decreased specifically in the hippocampus and amygdala of patients with MB and within the amygdala of patients with PA but otherwise remained normal after therapy. In the patients with tumor previously evaluated for IQ, regional ADC, but not CBF, correlated with IQ (R2 = 0.33-0.75). Conclusions The treatment for MB, but not PA, was associated with globally reduced CBF. Treatment in both tumor types was associated with diffusion abnormalities of the mesial temporal lobe structures. Despite significant perfusion abnormalities in patients with MB, diffusion, but not perfusion, correlated with cognitive outcomes.
Reproducible repair of Ebstein's malformation is challenging and numerous surgical techniques have been described. We reviewed our experience with the cone reconstruction.
Between June 2007 and ...December 2011, 89 patients (47 female; 53%) underwent cone reconstruction (median age 19 years; range, 19 days to 68 years). Indication for operation was progressive cardiomegaly in 43 (48%), cyanosis in 29 (33%), and heart failure in 13 (15%). Prior tricuspid valve repair was performed in 12 patients (13%). Severe tricuspid regurgitation (TR) was present in 75 patients (84%).
All patients underwent cone reconstruction (360-degree leaflet tissue repair anchored at true annulus). Modifications included ringed annuloplasty in 57 patients (64%), leaflet augmentation in 28 patients (31%), and autologous chordae in 17 patients (19%). Bidirectional cavopulmonary anastomosis was performed in 21 patients (24%). Early mortality occurred in 1 patient (1%). Early reoperation for recurrent TR occurred in 12 patients (13%); re-repair was performed in 6 patients (50%), and 6 (50%) required replacement. Mean follow-up was 19.7 ± 24.7 months. There was no late mortality or reoperation. At follow-up, 72 patients (87%) had no or mild TR, 9 (11%) had moderate TR, and 2 patients (2%) had severe TR. Ringed annuloplasty was associated with less than moderate TR at dismissal (p = 0.01).
The learning curve for cone reconstruction is steep, but early mortality is low. Cone reconstruction with ringed annuloplasty results in less TR and should be used whenever possible. Longer follow-up is essential to determine late durability of cone reconstruction.
Infants with perinatal sentinel events in the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network Hypothermia for Encephalopathy Trial had more ...basal ganglia and thalamus lesions on brain magnetic resonance imaging but similar neurodevelopmental outcomes at 18 months of age than infants without perinatal sentinel events. Outcomes correlated with the neonatal magnetic resonance imaging findings. Trial registration ClinicalTrials.gov : NCT00005772.
Because of the controversy involving the determination of child abuse, or nonaccidental injury (NAI), radiologists must be familiar with the issues, literature, and principles of evidence-based ...medicine to understand the role of imaging. Children with suspected NAI must receive protective evaluation along with a timely and complete clinical and imaging work-up. Imaging findings cannot stand alone and must be correlated with clinical findings, laboratory testing, and pathologic and forensic examinations. Only the child protection investigation may provide the basis for inflicted injury in the context of supportive clinical, imaging, biomechanical, or pathology findings.
Abstract Background Predicting treatment response to chemo-radiotherapy (CRT) in esophageal cancer remains an unrealized goal despite studies linking constellations of genes to prognosis. We aimed to ...determine if specific expression profiles are associated with pathologic complete response (pCR) after neoadjuvant CRT. Methods Eleven genes previously associated with esophageal cancer prognosis were identified. Esophageal adenocarcinoma (EAC) patients treated with neoadjuvant CRT and esophagectomy were included. Patients were classified into two groups: pCR and no-or-incomplete response (NR). Polymerase chain reaction was used to evaluate gene expression. Omnibus testing was applied to overall gene expression differences between groups, and log-rank tests compared individual genes. Results Eleven pCR and eighteen NR patients were analyzed. Combined expression profiles were significantly different between pCR and NR groups (p < 0.01). The gene CCL28 was over-expressed in pCR patients (Log-HR: 1.53, 95%CI: 0.46–2.59, p = 0.005), and DKK3 was under-expressed in pCR (Log-HR: −1.03 95%CI: −1.97, −0.10, p = 0.031). Conclusion EAC tumors that demonstrated a pCR have genetic profiles that are significantly different from typical NR profiles. The genes CCL28 and DKK3 are potential predictors of treatment response.
Objective To determine clinical and biochemical factors influencing cerebral edema formation during diabetic ketoacidosis (DKA) in children. Study design We used magnetic resonance diffusion-weighted ...imaging to quantify edema formation. We measured the apparent diffusion coefficient (ADC) of brain water during and after DKA treatment in 26 children and correlated ADC changes with clinical and biochemical variables. Results Mean ADC values were elevated during DKA treatment compared with baseline (8.13 ± 0.47 vs 7.74 ± 0.49 × 10−4 mm2 /sec, difference in means 0.40, 95% CI: 0.25 to 0.55, P < .001). Children with altered mental status during DKA had greater elevation in ADC. ADC elevation during DKA was positively correlated with initial serum urea nitrogen concentration (correlation coefficient 0.41, P = .03) and initial respiratory rate (correlation coefficient 0.61, P < .001). ADC elevation was not significantly correlated with initial serum glucose, sodium or effective osmolality, nor with changes in glucose, sodium or osmolality during treatment. Multivariable analyses identified the initial urea nitrogen concentration and respiratory rate as independently associated with ADC elevation. Conclusions The degree of edema formation during DKA in children is correlated with the degree of dehydration and hyperventilation at presentation, but not with factors related to initial osmolality or osmotic changes during treatment. These data support the hypothesis that CE is related to cerebral hypoperfusion during DKA, and that osmotic fluctuations during DKA treatment do not play a primary causal role.
Background Asthma is a complex disease characterized by striking ethnic disparities not explained entirely by environmental, social, cultural, or economic factors. Of the limited genetic studies ...performed on populations of African descent, notable differences in susceptibility allele frequencies have been observed. Objectives We sought to test the hypothesis that some genes might contribute to the profound disparities in asthma. Methods We performed a genome-wide association study in 2 independent populations of African ancestry (935 African American asthmatic cases and control subjects from the Baltimore–Washington, DC, area and 929 African Caribbean asthmatic subjects and their family members from Barbados) to identify single-nucleotide polymorphisms (SNPs) associated with asthma. Results A meta-analysis combining these 2 African-ancestry populations yielded 3 SNPs with a combined P value of less than 10−5 in genes of potential biologic relevance to asthma and allergic disease: rs10515807, mapping to the α-1B-adrenergic receptor (ADRA1B) gene on chromosome 5q33 (3.57 × 10−6 ); rs6052761, mapping to the prion-related protein (PRNP) gene on chromosome 20pter-p12 (2.27 × 10−6 ); and rs1435879, mapping to the dipeptidyl peptidase 10 (DPP10) gene on chromosome 2q12.3-q14.2. The generalizability of these findings was tested in family and case-control panels of United Kingdom and German origin, respectively, but none of the associations observed in the African groups were replicated in these European studies. Evidence for association was also examined in 4 additional case-control studies of African Americans; however, none of the SNPs implicated in the discovery population were replicated. Conclusions This study illustrates the complexity of identifying true associations for a complex and heterogeneous disease, such as asthma, in admixed populations, especially populations of African descent.
Background Proximity to roadways increases the risk of asthma in developed countries; however, relatively little is known about this relationship in developing countries, where rapid and uncontrolled ...growth of cities has resulted in urban sprawl and heavy traffic volumes. Objective We sought to determine the effect of distance from a heavily transited avenue on asthma symptoms and quantitative respiratory outcome measures in a periurban shantytown in Lima, Peru. Methods We enrolled 725 adolescents aged 13 to 15 years who were administered a survey on asthma symptoms and measured spirometry, response to allergy skin testing, and exhaled nitric oxide (eNO). We calculated distances from the main avenue for all households and measured indoor particulate matter in 100 households. We used multivariable regression to model the risk of asthma symptoms, risk of atopy, eNO levels, and FEV1 /forced vital capacity ratio as a function of distance. Results Compared against 384 meters, the odds of current asthma symptoms in households living within 100 meters increased by a factor of 2 ( P < .05). The odds of atopy increased by a factor of 1.07 for every 100-meter difference in the distance from the avenue ( P = .03). We found an inverse relationship in prebronchodilator FEV1 /forced vital capacity and distance to the avenue in female subjects ( P = .01) but not in male subjects. We did not find an association between eNO or household particulate matter levels and distance. Conclusion Living in close proximity to a high-traffic-density avenue in a periurban community in Peru was associated with a greater risk of asthma symptoms and atopy. Regulation of mobile-source pollutants in periurban areas of developing countries might help reduce the burden of asthma symptoms and atopy.
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