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Despite only 8% of cattle being found in Europe, European breeds dominate current genetic resources. This adversely impacts cattle research in other important global cattle breeds, especially those from Africa for which genomic resources are particularly limited, despite their disproportionate importance to the continent’s economies. To mitigate this issue, we have generated assemblies of African breeds, which have been integrated with genomic data for 294 diverse cattle into a graph genome that incorporates global cattle diversity. We illustrate how this more representative reference assembly contains an extra 116.1 Mb (4.2%) of sequence absent from the current Hereford sequence and consequently inaccessible to current studies. We further demonstrate how using this graph genome increases read mapping rates, reduces allelic biases and improves the agreement of structural variant calling with independent optical mapping data. Consequently, we present an improved, more representative, reference assembly that will improve global cattle research.

To formulate a classification system for foetal cortical formation abnormalities (CFAs) based on in utero magnetic resonance (iuMR) appearances and trial it in 356 cases. This retrospective study included all cases of foetal CFA diagnosed between 2000 and 2017 from seven centres in Italy and UK. All of the studies were reviewed by a panel of paediatric neuroradiologists experienced in iuMR with the aid of an algorithm designed to categorise the abnormalities. Consensus expert review confirmed 356 foetuses with CFA and the first level of classification distinguished bilateral CFA (229/356–64%) from unilateral CFA (127/356–36%) cases with sub-classification of the bilateral cases into asymmetric (65/356–18%) and symmetric (164/356–46%) involvement. There was a statistically significant excess of foetuses with small head size, e.g. 17% of the cohort had a bi-parietal diameter

Febrile infection-related epilepsy syndrome (FIRES) is a rare severe epileptic syndrome occurring in previously healthy children and characterized by refractory status epilepticus (SE) following a febrile illness. Brain imaging findings in affected patients have been reported in few case series and some case reports. This article is a comprehensive review of the magnetic resonance imaging (MRI) characteristics in all reported patients with a diagnosis of FIRES, describing the findings in the acute and chronic phases of the disease, and discussing possible pathogenesis and radiologic differential diagnoses. Most of the patients had normal brain scans in the acute phase (61%) and about 25% of the patients reported in literature had abnormalities in the temporal lobes. Changes in the basal ganglia and rarely in thalami or brainstem have also been described, as well as diffuse cerebral edema in a minority of patients during the acute phase. The chronic phase of the disease was characterized by atrophic changes and evidence of mesiotemporal sclerosis. An understanding of these MRI abnormalities is necessary to support the diagnosis of FIRES and exclude mimics.

Background The ALDH7A1 gene is known to be responsible for autosomal recessive pyridoxine-dependent epilepsy (OMIM 266100). The phenotypic spectrum of ALDH7A1 mutations is very heterogeneous ranging from refractory epilepsy and neurodevelopmental delay, to multisystem neonatal disorder. Aim The present study aims at describing the phenotype associated with a novel homozygous ALDH7A1 mutation and the spectrum of brain malformations associated with pyridoxine-dependent epilepsy. Methods We conducted a literature review on the Internet database Pubmed (up to November 2017) searching for ALDH7A1 mutations associated with brain malformations and brain MRI findings. Results We present the case of two siblings, children of related parents. The proband presented neonatal focal seizures not responding to conventional antiepileptic drugs. Electroencephalography showed a suppression burst pattern and several multifocal ictal patterns, responsive to pyridoxine. Brain MRI was normal. Molecular analysis by targeted next-generation sequencing panel for epileptic encephalopathy disclosed a homozygous missense mutation of ALDH7A1. The same mutation was then found in a stored sample of DNA from peripheral blood of an older sister dead 3 years earlier. This girl presented a complex brain malformation diagnosed with a foetal MRI and had neonatal refractory seizures with suppression burst pattern. She died at 6 months of age. Literature review The brain abnormalities most frequently reported in pyridoxine-dependent epilepsy include: agenesia/hypoplasia of the corpus callosum, not specific white matter abnormalities, large cisterna magna, ventriculomegaly, haemorrhages, cerebellum hypoplasia/dysplasia, and, more rarely, dysplasia of the brainstem and hydrocephalus. Discussion and conclusions ALDH7A1 mutations have been associated to different brain abnormalities, documented by MRI only in few cases. The study cases expand the clinical spectrum of ALDH7A1 associated conditions, suggesting to look for ALDH7A1 mutations not only in classical phenotypes but also in patients with brain malformations, mainly if there is a response to a pyridoxine trial.

Males and females present differences in complex traits and in the risk of a wide array of diseases. Genotype by sex (GxS) interactions are thought to account for some of these differences. However, the extent and basis of GxS are poorly understood. In the present study, we provide insights into both the scope and the mechanism of GxS across the genome of about 450,000 individuals of European ancestry and 530 complex traits in the UK Biobank. We found small yet widespread differences in genetic architecture across traits. We also found that, in some cases, sex-agnostic analyses may be missing trait-associated loci and looked into possible improvements in the prediction of high-level phenotypes. Finally, we studied the potential functional role of the differences observed through sex-biased gene expression and gene-level analyses. Our results suggest the need to consider sex-aware analyses for future studies to shed light onto possible sex-specific molecular mechanisms.

BACKGROUND AND PURPOSE: Walker-Warburg syndrome, muscle-eye-brain disease, and Fukuyama congenital muscular dystrophy are α-dystroglycan–related muscular disorders associated with brain malformations and eye abnormalities in which no structural inner ear abnormality has been described radiologically. We collected patients from 6 tertiary pediatric hospitals and reported the radiologic features and frequency of inner ear dysplasias. MATERIALS AND METHODS: Patients previously diagnosed clinicoradiologically with Walker-Warburg syndrome, muscle-eye-brain disease, or Fukuyama congenital muscular dystrophy were included. We recorded the pathogenic variant, when available. Brain MR imaging and/or CT findings were reviewed in consensus, and inner ear anomalies were classified according to previous description in the literature. We then correlated the clinicoradiologic phenotype with the inner ear phenotype. RESULTS: Thirteen patients fulfilled the criteria for the Walker-Warburg syndrome phenotype, 8 for muscle-eye-brain disease, and 3 for Fukuyama congenital muscular dystrophy. A dysplastic cochlea was demonstrated in 17/24. The most frequent finding was a pronounced cochlear hypoplasia type 4 with a very small anteriorly offset turn beyond the normal-appearing basal turn (12/13 patients with Walker-Warburg syndrome and 1/11 with muscle-eye-brain disease or Fukuyama congenital muscular dystophy). Two of 8 patients with muscle-eye-brain disease, 1/3 with Fukuyama congenital muscular dystrophy, and 1/13 with Walker-Warburg syndrome showed a less severe cochlear hypoplasia type 4. The remaining patients without Walker-Warburg syndrome were healthy. The vestibule and lateral semicircular canals of all patients were normal. Cranial nerve VIII was present in all patients with diagnostic MR imaging. CONCLUSIONS: Most patients with the severe α‐dystroglycanopathy Walker-Warburg syndrome phenotype have a highly characteristic cochlear hypoplasia type 4. Patients with the milder variants, muscle-eye-brain disease and Fukuyama congenital muscular dystrophy, more frequently have a normal cochlea or milder forms of hypoplasia.

To report feasibility, safety, and technical advantages of flat-detector computed tomography perfusion (FD-CTP) during balloon test occlusion (BTO) angiography studies, 10 patients patients scheduled for BTO were evaluated. Cerebral blood volume maps were extracted from FD-CTP images acquired during the test. The FD-CTP perfusion combined with BTO is feasible and safe in intracranial tumor, and aneurysm cases in which vessel sacrifice should be considered.

Epigenetic mechanisms may provide a novel prospective of bobcat (

BACKGROUND AND PURPOSE: Evaluation of biometry is a fundamental step in prenatal brain MR imaging. While different studies have reported reference centiles for MR imaging biometric data of fetuses in the late second and third trimesters of gestation, no one has reported them in fetuses in the early second trimester. We report centiles of normal MR imaging linear biometric data of a large cohort of fetal brains within 24 weeks of gestation. MATERIALS AND METHODS: From the data bases of 2 referral centers of fetal medicine, accounting for 3850 examinations, we retrospectively collected 169 prenatal brain MR imaging examinations of singleton pregnancies, between 20 and 24 weeks of gestational age, with normal brain anatomy at MR imaging and normal postnatal neurologic development. To trace the reference centiles, we used the CG-LMS method. RESULTS: Reference biometric centiles for the developing structures of the cerebrum, cerebellum, brain stem, and theca were obtained. The overall interassessor agreement was adequate for all measurements. CONCLUSIONS: Reference biometric centiles of the brain structures in fetuses between 20 and 24 weeks of gestational age may be a reliable tool in assessing fetal brain development.

We report a retrospective comparison between bi-dimensional RANO criteria and manual volumetric segmentation (MVS) in pediatric low-grade gliomas. MRI FLAIR or T1 post contrast images were used for assessment of tumor response. Seventy patients were included in this single center study, for each patient two scans were assessed (“time 0” and “end of therapy”) and response to therapy was evaluated for both methods. Inter-reader variability and average time for volumetric assessment were also calculated. Fourteen (20%) of the 70 patients had discordant results in terms of response assessment between the bi-dimensional measurements and MVS. All volumetric response assessments were in keeping with the subjective analysis of tumor (radiology report). Of the 14 patients, 6 had stable disease (SD) on MVS and progressive disease (PD) on 2D assessment, 5 patients had SD on MVS and partial response (PR) on 2D assessment, 2 patients had PD on MVS and SD on 2D assessment, and 1 patient had PR on MVS and SD on 2D analysis. The number of discordant results rises to 21(30%) if minor response is integrated in the response assessment. MVS was relatively fast and showed high inter-reader concordance. Our analysis shows that therapeutic response classification may change in a significant number of children by performing a volumetric tumor assessment. Furthermore, MVS is not particularly time consuming and has very good inter-reader concordance.

Patients with X-linked deafness carry mutations in the POU3F4 gene and have pathognomonic inner ear malformations characterised by symmetrical incomplete partition type 3 (absent modiolus and lamina spiralis but preserved interscalar septum in a normal-sized cochlea) and large internal auditory meatus (IAM) with an increased risk of gusher during stapes surgery. We describe a range of fairly characteristic malformations in the hypothalamus of some patients with this rare condition, ranging from subtle asymmetric appearance and thickening of the tuber cinereum to more marked hypothalamic enlargement. We discuss the role of POU3F4 in the normal development of both the inner ear and hypothalamus and the proposed pathophysiology of incomplete partition type 3.

Background International standard panels of single nucleotide polymorphisms (SNPs) have replaced microsatellites in several species for parentage assessment and assignment (PA) purposes. However, such a resource is still lacking in goats. The application of a cheap tool for PA would help the management of goat populations by improving the reliability of pedigree registration and, consequently, allow a better implementation of breeding schemes or conservation programs. Results Using data from the current GoatSNP50 chip, starting from a worldwide dataset of more than 4000 animals belonging to more than 140 breeds and populations from the AdaptMap initiative, we selected a panel of 195 SNPs. The assignment rate of this panel was up to 100% on an additional dataset that included 2000 Alpine and Saanen animals and highly related candidate sires. Conclusions In this study, we defined a highly informative SNP panel, which will be publicly available to worldwide breeders and laboratories. Its development on such a large number of breeds and populations, together with validation on a second set of cosmopolitan breeds, makes it a promising and important genomic tool for the goat species. Electronic supplementary material The online version of this article (10.1186/s12711-018-0423-9) contains supplementary material, which is available to authorized users.

Macrocephaly is a relatively common clinical condition affecting up to 5% of the pediatric population. It is defined as an abnormally large head with an occipitofrontal circumference greater than 2 standard deviations above the mean for a given age and sex. Megalencephaly refers exclusively to brain overgrowth exceeding twice the standard deviation. Macrocephaly can be isolated and benign or may be the first indication of an underlying congenital, genetic, or acquired disorder, whereas megalencephaly is more often syndromic. Megalencephaly can be divided into 2 subtypes: metabolic and developmental, caused by genetic defects in cellular metabolism and alterations in signaling pathways, respectively. Neuroimaging plays an important role in the evaluation of macrocephaly, especially in the metabolic subtype which may not be overtly apparent clinically. This article outlines the diverse etiologies of macrocephaly, delineates their clinical and radiographic features, and suggests a clinicoradiological algorithm for evaluation.

Inner ear malformations are recognized by imaging in about 20% of children with congenital sensorineural hearing loss. Normal development of the inner ear structures can be affected by many factors, including genetic anomalies as well as environmental destructive causes (ischemic, infectious, radiation and more). Recently, histopathological studies have provided new insights on the anatomy and pathogenesis of inner ear malformations, especially regarding incomplete partition and cochlear hypoplasia (CH), for which different subtypes have been identified. Factors known for interfering with normal inner ear development are numerous and sometimes act simultaneously, making the understanding of their pathophysiology more challenging. Vascular supply from the internal auditory canal seems to be critical for normal development of internal structures of the labyrinth while a premature arrest in the spatial development of the cochlea due to genetic or toxic factors may result in short cochlea (i.e.: CH). The aim of this essay is to show 3 T MRI appearances of the different subtypes of CH and incomplete partition introduced in the new classification (findings summary in Table 1).

The introduction of therapeutic hypothermia for neonatal hypoxic-ischemic encephalopathy call for reevaluation of the prognostic role of SEPs. This study aimed to test the prognostic value of SEPs using as outcome measure MRI severity and patterns of injury. Neonates eligible for hypothermia were recruited from four Italian Centers if they performed SEP and MRI at 4–15 days of life. SEPs were scored as: normal (bilaterally recorded/unilaterally absent N20) or altered (bilaterally absent N20). The severity of brain injury was measured using a validated MRI scoring system for acute and sub-acute signal abnormalities. 58 neonates were included in the analysis. Bilaterally absent N20 was observed in 10/58 (17%); all had moderate/severe MRI abnormalities. Furthermore, 37 infants (62%) had normal MRI all with normal N20. The positive predictive value of SEP on MRI outcome was of 100%, while the negative predictive value 72%, sensitivity 43%, specificity 100%, with an accuracy of 78% (p Bilateral absence of cortical SEPs is associated with a moderate/severe MRI pattern of injury, as previously reported in non-cooled infants. The prognostic value of SEPs is not (or minimally) affected by hypothermia.

We conducted an extensive review of the literature relevant to inner ear measurements in normal and malformative conditions to select reproducible methods and normative ranges that may be used in clinical practice.A review of the published literature was performed in the English language using PubMed with appropriate keywords. We selected only those articles containing normative values of inner ear structures.The following measurements were identified as reproducible and sensitive for the diagnosis of inner malformations: cochlear height in coronal plane; maximal diameter of bony island of lateral semicircular canal; width of vestibular aqueduct: 1) at midpoint; 2) at operculum in axial plane; cochlear canal and cochlear width in multiplanar reconstructions (MPR)/axial; cochlear length. The following cutoffs for normal inner ears are proposed based on the comparative analysis of the literature: cochlea height:4.3 mm; lateral semicircular canal bony island:3 mm; vestibular aqueduct:0.9 (midpoint) and1.9 mm (operculum); cochlear canal (axial MPR):1.4 mm and2.5 mm; cochlear width (MPR):5.4 mm.Measurements of inner ear structures can help in the interpretation of computed tomography images. They increase the sensitivity in detecting inner ear malformations, especially cochlear hypoplasia now considered more common than previously thought.

A 17-month-old boy showing features of global developmental delay and visual impairment, despite physiologic head circumference growth (between the 50th and 85th centile), was admitted for investigations. On examination, he appeared alert, with pale optic discs, horizontal jerk nystagmus, spasticity, and small genitalia.

Spinal vascular malformations are uncommon yet important spinal pathologies commonly classified in congenital and acquired lesions. Spinal lipomas consist of three subtypes: intramedullary lipomas, lipomyelo(meningo)celes and lipomas of the filum. Although the association of spinal arteriovenous malformations (AVM) with other congenital anomalies is well known, the coexistence of dural arteriovenous fistulas (AVF) and tethered spinal cord is exceptionally rare and only eight cases have been reported. We present two cases from our institution and speculate on the possible origin of such a rare but insidious association. We review the current literature with a focus on possible pitfalls in diagnosis and treatment.

To compare the lung nodules’ detection of digital tomosynthesis (DTS) and computed tomography (CT) in the context of the SOS (Studio OSservazionale) prospective screening program for lung cancer detection. One hundred and thirty-two of the 1843 subjects enrolled in the SOS study underwent CT because non-calcified nodules with diameters larger than 5 mm and/or multiple nodules were present in DTS. Two expert radiologists reviewed the exams classifying the nodules based on their radiological appearance and their dimension. LUNG-RADS classification was applied to compare receiver operator characteristics curve between CT and DTS with respect to final diagnosis. CT was used as gold standard. DTS and CT detected 208 and 179 nodules in the 132 subjects, respectively. Of these 208 nodules, 189 (91%) were solid, partially solid, and ground glass opacity. CT confirmed 140/189 (74%) of these nodules but found 4 nodules that were not detected by DTS. DTS and CT were concordant in 62% of the cases applying the 5-point LUNG-RADS scale. The concordance rose to 86% on a suspicious/non-suspicious binary scale. The areas under the curve in receiver operator characteristics were 0.89 (95% CI 0.83–0.94) and 0.80 (95% CI 0.72–0.89) for CT and DTS, respectively. The mean effective dose was 0.09 ± 0.04 mSv for DTS and 4.90 ± 1.20 mSv for CT. The use of a common classification for nodule detection in DTS and CT helps in comparing the two technologies. DTS detected and correctly classified 74% of the nodules seen by CT but lost 4 nodules identified by CT. Concordance between DTS and CT rose to 86% of the nodules when considering LUNG-RADS on a binary scale.

Background and aim: The public opinion about the nursing profession can influence health service users, the work performance of nurses, health policies, and the choice to become a nurse. The aim of this study was to investigate the perception of nursing in modern society. Methods: A cross-sectional study was conducted with a sample of 398 participants belonging to four population groups: Very Important Persons (VIPs), general population, upper-school students, and nursing students. This phenomenon was assessed through the Nursing Attitude Questionnaire (NAQ) and several additional items. Results: The results highlighted that general population and nursing students showed a significantly better image of nurses than did VIPs and upper-school students. Conclusions: Overall, the sample acknowledged nurses fundamental connotations and functions, although secondary school students poorly recognized nurses’ professional autonomy, and VIPs’ judgements seemed to be more sensitive to the image of nurses given by mass media.

Cerebrovascular complications are frequent events in children with sickle cell disease, yet routinely used techniques such as Transcranial Doppler (TCD), Magnetic Resonance (MRI) and Angiography (MRA), insufficiently explain the cause of poor cognitive performances. Forty children with SS-Sβ° (mean age 8 years) underwent neurocognitive evaluation and comprehensive brain imaging assessment with TCD, MRI, MRA, Resting State (RS) Functional MRI with evaluation of the Default Mode Network (DMN). Sixteen healthy age-matched controls underwent MRI, MRA and RS functional MRI.Children with SCD display increased brain connectivity in the DMN even in the absence of alterations in standard imaging techniques. Patients with low neurocognitive scores presented higher brain connectivity compared to children without cognitive impairment or controls, suggesting an initial compensatory mechanism to maintain performances. In our cohort steady state haemoglobin level was not related to increased brain connectivity, but SatO2

OBJECTIVE. We examined the diagnostic accuracy of routine imaging studies (ultrasonography and micturating cystography) for predicting long-term parenchymal renal damage after a first febrile urinary tract infection.METHODS. This study addressed the secondary objective of a prospective trial evaluating different antibiotic regimens for the treatment of acute pyelonephritis. Data for 300 children ≤2 years of age, with normal prenatal ultrasound results, who completed the diagnostic follow-up evaluation (ultrasonography and technetium-99m-dimercaptosuccinic acid scanning within 10 days, cystography within 2 months, and repeat technetium-99m-dimercaptosuccinic acid scanning at 12 months to detect scarring) were analyzed. Outcome measures were sensitivity, specificity, and negative and positive predictive values for ultrasonography and cystography in predicting parenchymal renal damage on the 12-month technetium-99m-dimercaptosuccinic acid scans.RESULTS. The kidneys and urinary tracts were mostly normal. The acute technetium-99m-dimercaptosuccinic acid scans showed pyelonephritis in 54% of cases. Renal scarring developed in 15% of cases. The ultrasonographic and cystographic findings were poor predictors of long-term damage, showing minor sonographic abnormalities for 12 and reflux for 23 of the 45 children who subsequently developed scarring.CONCLUSIONS. The benefit of performing ultrasonography and scintigraphy in the acute phase or cystourethrography is minimal. Our findings support (1) technetium-99m-dimercaptosuccinic acid scintigraphy 6 months after infection to detect scarring that may be related to long-term hypertension, proteinuria, and renal function impairment (although the degree of scarring was generally minor and did not impair renal function) and (2) continued surveillance to identify recurrent urinary tract infections that may warrant further investigation.

BACKGROUND. Approximately 20% of patients who have hepatoblastoma (HB) still have unresectable disease after preoperative chemotherapy (POC). In these circumstances, orthotopic liver transplantation (OLT) should be performed 1 month after POC. The authors sought to identify presenting features that would predict unresectability in patients with HB and to provide suggestions for early referral and listing for OLT. METHODS. Notes, radiology films, and histology from patients who were treated over the previous 20 years were reviewed. Unfeasible resection was defined by bilobar involvement, vascular extension, and metastatic disease after POC. Failed conservative treatment (FCT) was used to categorize patients who were not disease-free with their native liver � 1 year after surgery. RESULTS. Of 28 patients who were studied, 14 patients underwent resection, and 10 patients required OLT. Four patients did not undergo any type of surgery because of tumor progression. Overall, the 5-year survival rate was 76% (95% confidence interval, 54.8–89%). Predictors of FCT were multifocality (P 5 .006), a high pretreatment extent of tumor (PRETEXT) score (III or IV; P 5 .006), portal vein involvement (P 5 .02), hepatic vein involvement (P 5 .02), or vena cava involvement (P 5 .05). Patients who achieved a curative resection presented at a younger age (median, 0.7 years vs 4.2 years, P 5 .02). Patients who had multifocal lesions and those who had an a-fetoprotein (aFP) level

Purpose This study was performed to develop a standardized methodology for the sonographic assessment of clubfoot at birth and at the end of both conservative treatment and surgical correction. Methods Forty-two congenital clubfeet and 42 normal feet were examined sonographically in the position of spontaneous alignment and during passive manual correction. Scans along 4 planes provided information relevant to the assessment: sagittal posterior, sagittal anterior, coronal lateral, and transverse. Results Sagittal posterior sonograms demonstrated the progressive gain of dorsiflexion ability during the different steps of treatment for clubfoot. Sagittal anterior sonograms could not demonstrate the normal alignment of the navicular in clubfeet because of the bone's medial displacement. On transverse sonograms, the talar head and the medially displaced navicular may lie on the same plane, depending on the severity of the deformity. Coronal lateral sonograms provided for estimation of the relationships between the calcaneus and cuboid, which were described by the calcaneal-cuboid angle. Conclusions Sonography is a promising technique for assessment and monitoring of clubfoot during treatment. The method described here yields accurate and reproducible information about the anatomy of the nonossified clubfoot, helping the orthopedic team decide on appropriate treatment steps. © 2004 Wiley Periodicals, Inc. J Clin Ultrasound 32:235–242, 2004; Published online in Wiley InterScience (www.interscience.wiley.com). DOI: 10.1002/jcu.20022

We report a case of fused testes in a patient with transverse testicular ectopia and persistent Mullerian duct syndrome. A laparoscopy performed to confirm the diagnosis showed a single vas deferens on the left side. Treatment included excision of the Mullerian remnant through a left inguinal incision and orchidopexy of the fused testes via the left inguinal canal after sectioning of the right internal spermatic vessels. Follow-up ultrasound has so far confirmed viability of both testes.

Renal calcification is a known complication of long-term furosemide therapy in infants with bronchopulmonary dysplasia (BPD). In a prospective study the clinical course and long-term renal sequelae of renal calcifications of 19 consecutive premature neonates (birthweight < 1250 g) with bronchopulmonary dysplasia who did not receive furosemide were examined. Infants were divided into two different groups on the basis of ultrasound evidence of renal calcifications (RC group) or absence of renal calcifications (NRC group). Serial examinations, performed at the age of 1, 2, 3, 6, 9 and 12 months, showed that 12 infants at the mean age of 68.5 +/- 12.8 days of life had renal calcifications (63%), and 3 of them had nephrolithiasis; 8 had bilateral renal calcifications. Among the 9 survivors, 2 had chronic renal calcifications at the age of 9 months; however, all normalized at the age of 12 months. Twelve infants received hydrochlorothiazide and spironolactone (63%), 17 had prolonged courses of xanthines and dexamethasone (89.5%), while furosemide was not part of the routine pharmacological administration. Statistical analysis showed that birthweight, gestational age, Apgar score and length of parenteral nutrition were comparable in the RC and NRC group infants. Mean serum creatinine, creatinine clearance, fractional sodium excretion and urinary calcium excretion values during the 12-month study period were comparable in the RC and NRC groups. Mechanical ventilation and hospital stay length were instead associated with renal calcification occurrence. The strongest indicator of renal calcification risk for this high-risk population is the severity of the unresolved acute lung disease, where different facets of respiratory management, other than the addition of furosemide, represent sufficient stimuli and renal injury to potentiate stone formation.

From March 1979 to December 1984, the Liotta low-profile porcine bioprosthesis was employed for mitral valve replacement in 71 patients to avoid potential left ventricle-prosthesis mismatch occasionally observed with the standard, high-profile, Hancock porcine xenograft. Follow-up of 61 operative survivors showed at 10 years an actuarial survival of 67% +/- 7%, freedom from thromboemboli of 96% +/- 2%, freedom from structural deterioration of 63% +/- 11% and freedom from all Liotta bioprosthesis-related complications of 53% +/- 10%. Complications related to excessive protrusion of the stent into the left ventricular cavity were eliminated with the Liotta bioprosthesis; the peculiar stent configuration, however, was responsible for an increased rate of structural deterioration requiring reoperation in 10 patients (2.8% +/- 0.9%/patient-year) at a mean interval of 76 +/- 18 months after mitral valve replacement (range, 45 to 106 months). Common findings in all explants were cusp prolapse, cusp tears, and commissural rupture related to various degrees of tissue calcification, constantly leading to severe prosthetic incompetence. As also shown experimentally, such structural changes have been attributed to increased systolic stresses on the closed cusps, favored by excessive reduction of the stent height. Our experience shows that the Liotta bioprosthesis used for mitral valve replacement does not provide any clear-cut advantage over standard porcine bioprostheses and that its long-term durability appears affected by the unique prosthetic design.

Background: Medical treatment of gallstones with ursodeoxycholic acid (UDCA) or chenodeoxycholic acid (CDCA) has not been evaluated in children. Aim: The purpose of this study was to assess the effectiveness of UDCA in the treatment of gallstones in children. Method: UDCA was used to treat 15 patients, (7 boys and 8 girls; mean age, 7.8 years; range, 3 months to 15 years) for 1 year. All had radiolucent stones with a maximum diameter of 10 mm and a normally contractile gallbladder. Results: The stones disappeared completely in two children but returned later. All symptomatic patients became symptom free. Conclusion: UDCA is ineffective in the treatment of gallstones in children except in terms of relieving symptoms while on treatment.

Veno-occlusive disease (VOD) is one of the most frequent complications after stem cell transplantation. We conducted a prospective survey of 244 hematopoietic stem cell transplants in children to determine the incidence of VOD, its main risk factors, treatment and effect on the transplant.Two hundred and forty-four hematopoietic stem cell transplants (HSCT) performed in 220 pediatric patients from 1993 to 2003 were evaluated. The series included 127 males and 93 females with a median age of 6.7 years at the time of transplantation.VOD was diagnosed following 26 of the 244 transplants (cumulative incidence 11%), but a higher incidence was found in patients with at least one known risk factor for VOD (cumulative incidence 20%). In multivariate analysis, risk factors for VOD were age6.7 years; type of VOD prophylaxis, and busulphan-containing conditioning regimens. Routine treatment of VOD was based on supportive care and, starting from 1999, defibrotide was used. All patients were monitored with daily Doppler ultrasound-(US) for early diagnosis of inversion of portal blood flow. Twelve patients developed inversion of portal flow (9 had severe VOD; 3 had moderate VOD) and were promptly started on fibrinolytic and anticoagulant therapy with heparin and recombinant tissue plasminogen activator (rt-PA). Hepatic flow reverted to normal in all 12 patients; only 4 patients ultimately developed multiorgan failure and died. The transplant-related-mortality (TRM) rate in patients with or without inversion of portal flow was 33% vs 7%, (p=0.1). The TRM in patients with or without VOD was 19% vs 8% (p=0.001).This study showed that younger age, type of VOD prophylaxis, and busulphan-based conditioning regimens are independent risk factors for VOD. Inversion of portal flow was found in 9 of 10 patients with severe VOD. Doppler US monitoring may be helpful in early identification of the patients with VOD-induced inversion of portal flow who might benefit from therapy with heparin and rt-PA.

In the pediatric population a broad spectrum of intrascrotal pathology ranging from congenital to neoplastic lesions present as a painless scrotal mass. The aim of our 10-year retrospective study was to review 71 pediatric cases of a painless scrotal mass to determine the overall and age specific prevalence of diseases manifesting as such masses.From 1980-1991, 71 patients 1 day to 16 years old with a painless scrotal mass underwent evaluation using 7.5 or 10 MHz. ultrasound probes with transverse and longitudinal sections.The painless scrotal mass was testicular in 61 cases (86%, 28 neoplasms, 27 congenital malformations, and 6 posttraumatic/inflammatory lesions) and extratesticular in 10 (14%, 5 neoplasms, 2 hematoceles, 2 pachyvaginitis and 1 sebaceous cyst). Patient age distribution showed 2 peaks at 0 to 1-year and 13 to 14-year intervals. More than a third of the painless scrotal masses (24 cases) were found during the first year of life, predominantly congenital anomalies (in utero torsion) and neoplasia. A total of 45 patients (63%) underwent surgery (orchiectomy in 39 and conservative treatment in 6) and a pathognomonic echo pattern allowed nonsurgical treatment in 26 (37%).Testicular ultrasound proved to be highly reliable in differentiating intratesticular from extratesticular lesions but it demonstrated poor specificity because of extensive overlap between benign and malignant pathologies. Therefore, testicular ultrasound changed the management of a few select cases of a painless scrotal mass (epididymal cysts/spermatoceles and in utero torsion).

Fetal gallstones were visualized sonographically in two cases at 30 and 37 weeks' gestation; follow-up scans at 2 and 3 months, respectively, disclosed their spontaneous resolution. The hypotheses advanced to explain the formation of echogenic material in the fetal gallbladder are reviewed, and the clinical utility of postnatal long-term sonographic follow-up is stressed.

Pericarbon is a new-generation bovine pericardial bioprosthesis designed to withstand mechanical wear. Following optimal in vitro testing and animal experiments, clinical trials were initiated in many European centers and explants sent to our department for pathological evaluation. This included gross, radiographic, histologic and ultrastructural investigations.Between 1986 and 1996, 24 bioprostheses (eight aortic, 11 mitral, two mitro-aortic, one tricuspid) were collected from 22 patients (10 males and 12 females; mean age 57.0 +/- 18.9 years) either at autopsy (nine) or reoperation (15).Ten bioprostheses explanted2 months after surgery were either normal or failed because of surgical problems or non-structural causes. Among the other 14 bioprostheses (mean placement 41.9 +/- 23.6 months; range: 7 to 90 months), structural deterioration occurred in seven and was due to dystrophic calcification with stenosis in five (three aortic, two mitral), mixed lesion in one (mitral), and incompetence in one by calcium-related commissural tear (mitral). At the ultrastructural level, calcification was detected either on cell debris or upon collagen fibers. No bioprosthesis failed because of fibrous tissue overgrowth. Of the remaining seven bioprostheses, vegetative endocarditis occurred in two, thrombosis in one, and aseptic paravalvular leak in one; whereas three showed no signs of dysfunction.This pathologic experience with the Pericarbon valve showed calcification to be the main cause of late structural failure, causing mainly cusp stiffness and bioprosthesis stenosis. Tissue rupture or abrupt dysfunction never occurred. Thus, prevention of mineralization remains the main challenge.

Acute rejection following orthotopic liver transplantation is a common problem despite current immunosuppressive regimens. Ursodeoxycholic acid (UDCA) has been shown in small, open-labeled studies to prevent rejection episodes, although its effects on complications such as infections, length of hospital stay, and survival have not been evaluated. We conducted a randomized, placebo-controlled, double-blind trial to determine if UDCA (10-15 mg/kg/d) added to a cyclosporine-based immunosuppressive regimen was associated with a decrease in the incidence of at least one episode of acute cellular rejection. Secondary end-points included determining differences in the total number of rejection episodes, the use of muromonab-CD3, the incidence of infections, length of hospital stay, and survival at 90 days and 1 year. Fifty-two patients were randomized, 28 to the treatment group and 24 to the placebo group. During the 3 months of the trial, there was no difference between the placebo and UDCA groups in the number of patients who were rejection-free; however, there were significantly fewer patients in the treatment group who had multiple episodes of acute rejection (0 vs. 6; P = .007). Patients in the treatment group experienced a significantly lower incidence of bacterial infections (4% vs. 29%; P = .02), shorter hospital stay (25 days vs. 34 days; P = .03), and better 90-day survival (100% vs. 83%; P = .04) and 1-year survival (93% vs. 79%). The addition of UDCA to a cyclosporine-based immunosuppressive regimen results in significantly fewer patients experiencing multiple episodes of rejection and improved survival at 90 days and at 1 year. The use of UDCA as adjuvant therapy for patients undergoing liver transplantation who are treated with a cyclosporine-based immunosuppressive regimen should be considered.

The aims of the present work were to assess the diagnostic accuracy of ultrasonographic evaluation of superficial lymph nodes in patients with cutaneous melanoma and to describe the sonographic characteristics which permit early detection of neoplastic nodal involvement. Eighty-seven patients (89 lymph node sites) were studied for approximately a 3-year period, with a minimal surveillance time of 1 year. The ultrasonographic imaging equipment utilized were a 10 MHz scanner with a mechanical and one with 10 MHz electronic linear probe. The characteristics considered indicative of possible metastatic involvement were: round shape (short to long axis ratio > 0.5), no central hilus, nodular areas within the lymph node, sinuosity of the lymph node edges and lymph node with regular morphology and echostructure but with maximum diameter greater than 3 cm. Generally inguinal and axillary lymph nodes are larger than cervical ones. Of the 89 sites explored, 32 were considered ‘suspect’. All 32 of these were subjected to cytology using ultrasound-guided, fine needle aspiration. The remaining 56 came in for a periodic control examination during a year. Thirteen of the 32 ‘suspect’ lymph nodes proved positive at the pathologic examination. Two patients whose ultrasound diagnosis was negative developed metastases within 2 to 4 months (ultrasound false negatives). Our study indicates that there are sonographic features indicative of lymph node metastases from melanoma even in the early stages of the disease. Ultrasound scanning, therefore, is a useful diagnostic tool in the follow-up of melanoma patients, identifying which should be subjected to further testing with needle biopsy.

Nodular regenerative hyperplasia (NRH) of the liver is a condition of unknown origin, rarely occurring in children, usually accidentally discovered, described in association with a variety of clinical conditions and drugs. Confusion with other types of hepatic masses may pose a problem and for this reason NRH is considered a “tumor-like lesion.” Histologically it consists of single or multiple regenerative foci. Hepatic failure and rupture of the liver have been rarely described as complications in adults, and not in children, and malignant transformation has not been demonstrated. Neither surgical removal nor other treatment is needed. These features are described as they were found in two patients we encountered. © 1996 Wiley-Liss, Inc.

The Liotta low profile porcine bioprosthesis (LBP) was designed in order to minimize complications due to excessive protrusion of the stent prongs in the left ventricle.From April 1984 to November 1993, 25 LBP surgical explants were available for pathology study, which included gross and X-ray evaluations. Reoperation was performed after a mean period of 95 +/- 25 months (range 46 to 143 months), in five males and 20 females (mean age at implantation 51.1 +/- 11.4 years).The cause of failure was stenosis due to cusp stiffness caused by dystrophic calcification in one and incompetence in 24 LBPs. In only one case was incompetence ascribable to endocarditis; in the remaining 23 the mechanism of regurgitation was due to commissural tearing (21 LBPs), commissural dehiscence (one LBP) and both tears and dehiscence (one LBP). Overall, 28 commissural tears were observed: 20 involved the right coronary cusp, eight the left coronary cusp, and none the non-coronary cusp. The anterior commissure was most frequently involved by tears (n = 17) followed by the right posterior (n = 9) and the left posterior (n = 2). Tears were calcium-related in all but two cases. Calcific deposits were observed in each explant, involving a total of 62 commissural attachments, 17 cusp bodies and five right muscular shelves.In conclusion, valve regurgitation is the usual mode of LBP failure in the mitral position; commissural tearing of the right coronary cusp was the most common cause of valve regurgitation, and occurred even in the presence of pin-point calcification. These pathologic findings seem to confirm that low profile design, which implies bulging of the right coronary cusp, entails the risk of increased stress at the commissures, accelerated calcification and tearing.

We studied the aortic root (wall, semilunar cusp, septal myocardium) in 37 patients (29 male and 8 female; mean age; 41 years) who died 2 to 4,380 days (mean, 398 days) after heart (n = 34) and heart-lung (n = 3) transplantation. The aim of the study was to assess tissue viability, graft-host biological interaction, and cusp mineralization with time. Study methods included gross inspection and photos of each specimen, microradiography, histology and immunohistochemistry, scanning and transmission electron microscopy, and atomic absorption spectroscopy. There were no cases of valve dysfunction; in particular, cusp tears or perforations never occurred. Only 1 valve, in place for 12 years, had a pin-point calcification visible to the naked eye. Optimal preservation of the tissue components (endothelium, fibroblasts, collagen and elastic fibers, proteoglycans, intrinsic nervous ganglia) was observed at both short and long term. Concomitant acute rejection of valve leaflets and myocardium was seen in 7, mild valve thickening in 14, myxoid degeneration in 4, and graft aortic atherosclerosis in 26. Mineralization was negligible and was not progressive with time. No linear correlation was found between mineralization and number of acute rejections. In conclusion, we observed optimal cusp viability and integrity even at long term, concomitant valve and myocardium rejection with no valvular sequelae, and negligible, non-progressive cusp calcification. Donor-recipient blood group matching, heart-beating donor, and chronic immunosuppression are the reasonable explanations of the optimal durability of the aortic valve after heart transplantation.

We present two children, respectively five and six years old, misdiagnosed and treated as asthmatics in allergological centers. After admission to our department, endobronchial inflammatory pseudotumor and lung tuberculosis were diagnosed respectively. While endobronchial pseudotumor is rather rare, lung tuberculosis is a less rare diagnosis that must be considered in patients with a history of persistent and recurrent coughing with or without wheezing, especially when there is no family history of atopical diseases and skin allergic tests are negative, and the social and economic conditions at risk.

Asymptomatic scrotal masses (ASM) in children constitute an entity of pathologies, ranging from congenital anomalies to neoplasms. Testicular ultrasound is the imaging modality of choice in the evaluation of ASM, although there is extensive overlap between benign and malignant lesions. Five children with ASM of benign origin are presented: 2 boys had extratesticular mass (one paratesticular lipoma and one voluminous sebaceous scrotal cyst); the remaining 3 patients had testicular mass (one supernumerary testis, one intratesticular cyst and one unilateral testicular hypertrophy). Basing on the ultrasonographic appearance, a certain diagnosis of benign lesion was made only in the last 2 cases; the remaining patients underwent explorative inguinotomy in order to rule out any malignancy. Some guidelines for proper diagnosis of ASM in childhood are proposed by the authors. However, at least in children, testicular preservation should not be based only on the sonographic findings, and surgical exploration is mandatory whenever the nature of the lesion remains unclear.

Objectives . This study aimed to assess the clinical performance and durability of a new generation of porcine valve, the Hancock II bioprosthesis, at intermediate-term follow-up. Background . Standard porcine bioprostheses undergo progressive structural deterioration, mainly due to cusp and commissural calcification, affecting durability and requiring reoperation. The Hancock II bioprosthesis, which is currently undergoing clinical investigation, is made from a porcine aortic valve treated with a calcium-retarding agent (sodium dodecyl sulfate [T6]), which should delay onset of calcification and increase durability. Methods . From May 1983 to December 1992, we used the Hancock II bioprosthesis in aortic (59 patients), mitral (101 patients) and mitral-aortic (25 patients) valve replacement procedures. Postoperative follow-up ranged from 0.1 to 8.7 years (mean [±SD] 4.5 ± 2.6 years) and was 100% complete. Freedom from major postoperative events was calculated at 7 years for patients with aortic valve replacement and at 8 years for those with mitral and mitral-aortic valve replacement. Results . The actuarial survival rate was 48 ± 10%, 76 ± 3% and 63 ± 6%; freedom from valve-related mortality was 91 ± 4%, 94 ± 2% and 89 ± 6%; freedom from thromboembolism was 80 ± 11%, 90 ± 2% and 79 ± 7%; and freedom from reoperation was 100%, 97 ± 1% and 89 ± 6% after aortic, mitral and mitral-aortic valve replacement, respectively. No structural valve deterioration occurred. Conclusions . At intermediate-term follow-up the Hancock II bioprosthesis showed excellent durability in all positions. However, the effectiveness of anticalcification treatment must be assessed with longer follow-up studies.

Fetus in fetu is a rare pathological condition, presenting as a congenital tumor. It consists of a malformed parasitic twin that is found within the body of its sibling. Less than 70 cases have been reported and in most of them a definite diagnosis was only made during surgery. We present a case with two fetuses in the retroperitoneum and describe the criteria to be kept in mind for a correct preoperative diagnosis, using the current imaging modalities.

From January 1989 through December 1990, 74 patients were admitted to our urban level I trauma center with injuries inflicted by baseball bats. We investigated the demographics and dynamics of injury in these patients by retrospective analysis of the patient's medical record and Trauma Registry data. The average victim was 30 years old. Ninety-two percent of the patients were male, and approximately 89% tested positive for substance abuse. Injury to both the head and body occurred in 80% of our patients, isolated head injury occurred in 42%. Twenty percent suffered injury to the body only. On admission, 7% went directly to the operating suite, 16% were admitted to the trauma ICU, one patient was admitted to the pediatric ICU, and the remainder were admitted to the floor shock/trauma unit. These patients had a length of stay (LOS) that was not significantly different than the LOS for patients with penetrating trauma or the general trauma population. The mean Trauma Score was 13.8 (range, 6-16), and the average Injury Severity Score was 10.5 (range, 1-34). The mortality in our study was 3%. Four percent of the patients were left with some degree of permanent disability. Intentionally inflicted injury is most commonly seen in the thorax and abdomen. In contrast, head injury was evident in 80% of our patients with baseball bat injury. This represents a departure from classic patterns of violent injury.

Durability of a new bioprosthesis, the Meadox-Gabbay unileaflet pericardial xenograft, was evaluated by reviewing a series of 12 patients who received this device in the mitral position from 1983 to 1985. Bioprosthetic failure necessitated reoperation in 5 patients 21, 22, 53, 66, and 81 months after placement. Three patients died of cardiac failure after 31, 52, and 70 months; no postmortem examinations were done. In 2 of the 3 patients, an echocardiographic study had shown signs of valvular dysfunction. Pathological examination of five available explants revealed the presence of redundancy and stretching of the single pericardial leaflet in all of them; in one, this lesion alone caused severe prosthetic incompetence. Other pathological findings included cusp and commissural calcification and commissural tears with or without calcification. Histologic examination and electron microscopy showed intrinsic calcification involving both collagen bundles and cellular debris and various degrees of collagen disruption. In this limited series of patients, the Meadox-Gabbay pericardial xenograft demonstrated various modes of failure that markedly impair its durability and render it unsuitable as a cardiac valve substitute.

The long-term prognosis of extrahepatic biliary atresia after surgical restoration of bile flow is still controversial. An ongoing process of cirrhosis and the development of portal hypertension continue to create frequent and frustrating management problems. Clinical features, hepatic function, echotomography aspect, calcium-phosphorus metabolism and serum levels of 25-OH-D-3 were evaluated in 12 anicteric patients with extrahepatic biliary atresia successfully treated in a period from 1974 through 1987. Seven of these children had a total of 21 episodes of cholangitis. In five patients liver biopsy, obtained at the time of the external diversion closure, showed a biliary cirrhosis. Growth, development and hepatic function were normal in all children studied; one patient had esophageal varices. The serum levels of 25-OH-D3 in patients without oral supplementation of vitamin D are lower than normal. This deficit can be corrected by oral administration of vitamin D. Our study revealed that the children with successful portoenterostomy appeared to thrive normally and that they tolerated the relatively mild liver damage. We believe that Kasai operation should be done in all patients with extrahepatic biliary atresia and that the liver transplantation is to be reserved only in those with unsuccessful Kasai. In our experience external diversion was not useful to prevent cholangitis and moreover it complicates the hepatectomy in case of transplantation.

Eighty-seven pediatric patients with suspected acute appendicitis underwent high-resolution US with graded abdominal compression. The study was limited to the patients with a questionable clinical diagnosis, accounting for about 40% of the patients examined for acute appendicitis in our Institution. US had 87.3% accuracy, 81.5% sensitivity, and 90% specificity. The main US findings in the positive cases were: visualization of the appendix as a tubular non-compressible structure, with a diameter of 5 mm or more, symmetric/asymmetric wall thickening, possible presence of appendicoliths and variable appearance of the central echogenic layer (preserved, doubled for lumen dilatation, partially/totally lost). The above US findings were grouped in 3 basic patterns: type I (thickened appendix with no structural abnormalities) appeared to be related to non-suppurative and phlegmonous acute appendicitis; type II (detectable appendiceal abnormalities) was observed both in phlegmonous and in suppurative acute appendicitis; type III (pericecal complex mass, frequently with appendicoliths) was found in all cases of periappendiceal abscess. In our experience, the use of US in the diagnosis of acute appendicitis in children allowed a reduction by about 2/3 in the rate of unnecessary laparotomies. Such a finding emerges from the comparison with the results obtained in the 2 years prior to the use of US. The technique also allowed an unquestionable diagnosis of acute appendicitis or periappendiceal abscess to be made in a number of clinically equivocal cases, thus avoiding potentially harmful delays in diagnosis. On the other hand, the incidence of false-negatives on US is not negligible, which calls for a cautious clinical and US evaluation of all equivocal cases following no typical US pattern.

Because little information is available regarding the clinical performance of the Hancock porcine bioprosthesis (JohnsonJohnson Cardiovascular, King of Prussia, Pa.) implanted in the tricuspid position, we reviewed the long-term follow-up of patients who had tricuspid valve replacement with this device. From March 1970 to December 1983, 45 patients had tricuspid valve replacement, either isolated (seven patients) or combined with replacement of other valves (38 patients) by means of a standard, glutaraldehyde-preserved Hancock porcine bioprosthesis. Follow-up ranged from 0.2 to 14.7 years (mean, 7.6 +/- 3.6 years) and was complete. The late mortality rate was 6.6% +/- 1.6%/pt-yr and the actuarial survival rate at 14 years was 23% +/- 9%. Reoperation because of structural deterioration of the tricuspid, the mitral, or both bioprostheses was performed in nine patients (3.7% +/- 1.2%/pt-yr) from 40 to 177 months (mean, 112 +/- 43 months) and resulted in no deaths. Actuarial freedom from structural deterioration of a Hancock tricuspid porcine bioprosthesis at 14 years is 68% +/- 13%. Morphologic examination of explanted porcine bioprostheses showed that those implanted in the tricuspid position had lower degrees of calcification and less severe structural changes than those simultaneously explanted from the mitral position. We conclude that the Hancock porcine bioprosthesis has an acceptable long-term durability and satisfactory performance after tricuspid valve replacement, and we continue to favor its use in the tricuspid position even in association with mechanical prostheses in the left side of the heart.