Vitamin D deficiency and sudden unexpected death in infancy and childhood: a cohort study.

We sought to (1) determine if there is an increased prevalence of vitamin D deficiency (VDD) in cases of sudden death in infancy and childhood; (2) establish whether there is a link between VDD and infection; and (3) assess if the level of vitamin D can be related to abnormalities in the skeletal survey and rib histology in our cohort. The postmortem reports of cases in which vitamin D levels were measured in 2009 and 2010 were retrieved. When parental consent for audit had been granted, rib histology and skeletal surveys were reviewed. Plasma 25-hydroxyvitamin D levels were measured in 41 postmortem cases. Ten (24.5%) had adequate levels, 5 (12%) had suboptimal levels, 16 (39%) had moderate deficiency, and 10 (24.5%) had severe deficiency. We had only 4 cases with VDD and infection. There were 25 cases of unexplained death in our cohort, and 76% of these had inadequate vitamin D levels. The rib histology was abnormal in 69% of cases that had inadequate vitamin D levels, while the radiology was abnormal in 19% of cases. A significant proportion of infants and children who died suddenly and unexpectedly had inadequate levels of vitamin D. We were unable to confirm or exclude an association between VDD and infection due to the small number of cases with confirmed infection. Further multicenter studies are needed to confirm our findings and explore possible associations between VDD and other known risk factors for sudden unexplained death in infancy and childhood.

Reduction of intussusception: defining a better index of successful non-operative treatment.

The reported non-operative reduction rate for intussusception is usually the proportion of attempted non-operative (radiological) reductions that succeed, which we term the "selective reduction rate." This value shows wide variation that may result from selection bias that is difficult to quantify because data regarding primary operative treatment are frequently lacking. The proportion of patients with late clinical presentation or pathological lead points can also distort the apparent efficacy of non-operative treatment. We found no definitions of outcome measures in the literature or practice guidelines to inform analysis. Based on analysis of our own audit data we derived a "composite reduction rate" from first principles that can account for variations in radiological and surgical treatment thresholds that might bias other measures of successful non-operative treatment. This index is the proportion of intussusceptions not requiring resection that are successfully reduced non-operatively. We propose that the composite reduction rate be used as a key component of standardised multidisciplinary outcome reporting for intussusception rather than the selective reduction rate. The reduced bias and confounding would allow fairer comparisons and lead to better outcome standards.

IMAGe syndrome: Case report with a previously unreported feature and review of published literature.

IMAGe syndrome is a rare condition, first reported by Vilain et al., in 1999, characterized by intrauterine growth restriction, metaphyseal dysplasia, congenital adrenal hypoplasia, and genital anomalies. Patients with this condition may present shortly after birth with severe adrenal insufficiency, which can be life-threatening if not recognized early and commenced on steroid replacement therapy. Other reported features in this condition include, hypercalciuria and/or hypercalcemia, craniosynostosis, cleft palate, and scoliosis. We report on a 7-year-old boy with IMAGe syndrome, who in addition to the features in the acronym also has bilateral sensorineural hearing loss which has not been reported in previously published cases of IMAGe syndrome. We discuss the clinical presentation in our patient and review the literature in this rare multisystem disorder.

Subdural hemorrhage, intradural hemorrhage and hypoxia in the pediatric and perinatal post mortem: are they related? An observational study combining the use of post mortem pathology and magnetic resonance imaging.

BACKGROUND AND PURPOSE: Controversies exist over the causes of intradural hemorrhages (IDH), subdural hemorrhages (SDH) and hypoxia. SDH is a recognised finding at perinatal and pediatric autopsy. We describe the occurrence of IDH, SDH, and hypoxia in these deaths using a combined approach of post mortem magnetic resonance imaging (PM MRI), autopsy examination and histology. MATERIAL AND METHODS: Forty-two cases (1 day to 4 years, mean 6.9 months) underwent PM MRI and autopsy. Two further children (8 and 32 month of age) underwent autopsy only. MRI was conducted with a 1.5 T Magnet with fast spin-echo T2 weighted images, the images were assessed for the presence of SDH, hypoxia and structural abnormalities. Hypoxia was defined by a low signal in the ventrolateral thalami and peri-rolandic regions on MRI. Edema was interpreted as early acute hypoxia. On histology, hypoxia was defined by the presence of hypoxic neurons. RESULTS: IDH was seen histologically in 35/39 cases: diffuse in 17 and focal in 18. On the PM MRI focal IDH was not distinguished, and DIDH was only retrospectively suggested as a low signal around the venous sinuses or prominent venous sinuses, predominantly in the posterior falx and tentorium. Confident identification on the MRI was not possible. 12/17 cases with DIDH were less than a week old. SDH was seen in 11 cases on PM MRI. SDH was seen at autopsy in the same 11 cases and in the 2 cases where no PM MRI was performed. DIDH was seen in all these cases on histological examination (except in 1 case where the dura had not been sampled). Acute hypoxia was present in 14/42 cases both on histology and MRI. In 1 case changes of hypoxia were seen on MRI only. In 7 cases the hypoxia was seen on histology only. 12/13 cases with SDH had features of hypoxia. Of the cases with DIDH on histology 14/17 had hypoxia (on MRI, histology, or both). CONCLUSION: IDH and SDH are frequent findings in the perinatal and pediatric autopsy. SDH was associated with a DIDH and was also frequently associated with hypoxia. Focal IDH was not identified at the PM MRI; it was associated with hypoxia (on MRI and/or on histology) in less than a quarter of cases. Our results exhibit an association between IDH, SDH and hypoxia in children dying of natural causes. The highest incidence is seen in the perinatal period.

A randomized, controlled dose-ranging study of risedronate in children with moderate and severe osteogenesis imperfecta.

Moderate to severe osteogenesis imperfecta is associated with multiple fractures in childhood. There are no published data regarding the effects of third-generation bisphosphonates in these children. This randomized study investigated which of three different doses of risedronate was most effective in reducing fracture incidence. We randomly assigned 53 children with moderate to severe osteogenesis imperfecta to receive 0.2, 1, or 2 mg/kg per week of risedronate. We assessed safety, fracture incidence, and bone measurement outcomes at 3, 6, 12, 18, and 24 months. At 24 months, 69% of children assigned 0.2 mg/kg per week had had new fractures compared with 44% receiving 1 mg/kg per week and 75% receiving 2 mg/kg per week. Poisson regression with age and prior fracture as covariates showed that there was no difference in incident nonvertebral fracture between groups. Fracture rate diminished in each group during the trial compared with previous the 2 years (p = .005). Lumbar spine bone mineral density increased significantly (p = .009) only in the 2 mg/kg per week group. Long bone bowing deformities reduced more in children receiving 1 or 2 mg/kg per week of risedronate [odds ratio (OR) 0.67, 95% confidence interval (CI) 0.48-0.93 per unit increase in risedronate dose, p = .015]. There were no serious adverse events. Bone mass increased and bowing deformities reduced with increasing risedronate dose. Children suffered fewer fractures irrespective of risedronate dose. The most appropriate dose of risedronate for children with moderate to severe osteogenesis imperfecta in this study was 2 mg/kg per week.

Fluoroscopy-guided insertion of nasojejunal tubes in children - setting local diagnostic reference levels.

BACKGROUND: Little is known about the radiation burden from fluoroscopy-guided insertions of nasojejunal tubes (NJTs) in children. There are no recommended or published standards of diagnostic reference levels (DRLs) available. OBJECTIVE: To establish reference dose area product (DAP) levels for the fluoroscopy-guided insertion of nasojejunal tubes as a basis for setting DRLs for children. In addition, we wanted to assess our local practice and determine the success and complication rates associated with this procedure. MATERIALS AND METHODS: Children who had NJT insertion procedures were identified retrospectively from the fluoroscopy database. The age of the child at the time of the procedure, DAP, screening time, outcome of the procedure, and any complications were recorded for each procedure. As the radiation dose depends on the size of the child, the children were assigned to three different age groups. The sample size, mean, median and third-quartile DAPs were calculated for each group. The third-quartile values were used to establish the DRLs. RESULTS: Of 186 procedures performed, 172 were successful on the first attempt. These were performed in a total of 43 children with 60% having multiple insertions over time. The third-quartile DAPs were as follows for each age group: 0-12 months, 2.6 cGy cm(2); 1-7 years, 2.45 cGy cm(2); >8 years, 14.6 cGy cm(2). High DAP readings were obtained in the 0-12 months (n = 4) and >8 years (n = 2) age groups. No immediate complications were recorded. CONCLUSION: Fluoroscopy-guided insertion of NJTs is a highly successful procedure in a selected population of children and is associated with a low complication rate. The radiation dose per procedure is relatively low.

Inflammatory myofibroblastic tumor of the pancreas: a case report of 2 pediatric cases--steroids or surgery?

Inflammatory pseudotumors also termed inflammatory myofibroblastic tumors (IMTs) are rare, benign, solid lesions of unclear etiology more usually found in the lung and very rarely in the pancreas. We report 2 cases and outline our management for each. The first case was treated surgically, whereas the second was treated with high-dose steroids. This represents the first reported case whereby steroid treatment has been successful in pancreatic IMT.

Fetal megalourethra associated with hypoplastic left heart and imperforate anus: a previously unreported association.

We report two cases of a fetus with a megalourethra associated with a hypoplastic left heart, dilated and echogenic bowels, vesico-colonic fistula and an imperforate anus. This combination of fetal abnormalities may represent an unclassified syndrome.

Intra-abdominal splenosis following laparoscopic splenectomy causing recurrence in a child with chronic immune thrombocytopenic purpura.

In this paper, we present the case of a 12-year-old boy with refractory, symptomatic immune thrombocytopenic purpura (ITP) who underwent a laparoscopic splenectomy (LS). During morcellation of the spleen the retrieval bag ruptured. Thirteen (13) months postoperatively, the patient developed further symptoms and was found to be thrombocytopenic. Tc-99m heat-damaged red blood cell scintigraphy showed an accumulation of heat-damaged red cells in the upper left quadrant, raising the possibility of missed accessory spleen. Laparoscopic exploration revealed widespread intra-abdominal splenosis, and a therapeutic omentectomy was carried out. Fourteen (14) months post-surgery, platelet counts improved and the patient remains well. Following an elective splenectomy, a relapse in ITP may be the result of missed accessory spleen or splenosis; in others, it may the result of ongoing platelet consumption in non-splenic, reticulo-endothelial tissue. During LS, consideration must therefore be given to the risk of not only leaving additional splenic tissue behind, but also to the possibility of accidental autotransplantation, such as that from laparoscopic bag rupture. The risk of rupture can be minimized by using blunt instruments and stronger bag materials. If a rupture does occur, immediate suction and a thorough search for splenic fragments must be undertaken. Further development is needed into new techniques for organ retrieval and stronger bag materials.

Brachydactyly with extrahepatic biliary atresia, patent ductus arteriosus and seizures--a new syndrome?

Brachydactyly is a relatively common congenital anomaly and can be associated with many other malformations. However, brachydactyly in association with biliary atresia is rare. We present a male child with strikingly symmetrical brachydactyly and nail hypoplasia, extrahepatic biliary atresia, patent ductus arteriosus, seizures, developmental delay and cataracts. This combination of features has not previously been described and we suggest that this case represents a new syndrome.

Development of a real-time polymerase chain reaction assay for prediction of the uptake of meta-[(131)I]iodobenzylguanidine by neuroblastoma tumors.

PURPOSE: The suitability of neuroblastoma patients for therapy using radiolabeled meta-iodobenzylguanidine (MIBG) is determined by scintigraphy after the administration of a tracer dose of radioiodinated MIBG whose uptake is dependent upon the cellular expression of the noradrenaline transporter (NAT). As a possible alternative to gamma camera imaging, we developed a novel molecular assay of NAT expression. mRNA extracted from neuroblastoma biopsy samples, obtained retrospectively, was reverse transcribed, and NAT-specific cDNA was quantified by real-time PCR, referenced against the expression of the housekeeping gene glyceraldehyde-3-phosphate dehydrogenase. EXPERMENTAL DESIGN: Tumor specimens from 54 neuroblastoma patients were analyzed using real-time PCR, and NAT expression was compared with the corresponding diagnostic scintigrams. RESULTS: Forty-eight of 54 (89%) of tumors showed MIBG uptake by scintigraphy. NAT expression was found to be significantly associated with MIBG uptake (P < 0.0001, Fisher's exact test). None of the samples from the six tumors that failed to concentrate MIBG expressed detectable levels of the NAT (specificity = 1.0). However, of the 48 MIBG uptake-positive tumors, only 43 (90%) expressed NAT (sensitivity = 0.9). The real-time PCR test has a positive predictive value of 1.0 but a negative predictive value of 0.55. CONCLUSIONS: The results indicate that whereas this method has substantial ability to predict the capacity of neuroblastoma tumors to accumulate MIBG, confirmation is required in prospective studies to determine more accurately the predictive strength of the test and its role in the management of patients with neuroblastoma.