Analysis of Staphylococcus aureus Transcriptome in Pediatric Soft Tissue Abscesses and Comparison to Murine Infections.

A comprehensive understanding of how Staphylococcus aureus adapts to cause infections in humans can inform development of diagnostic, therapeutic, and preventive approaches. Expression analysis of clinical strain libraries depicts in vitro conditions that differ from those in human infection, but low bacterial burden and the requirement for reverse transcription or nucleic acid amplification complicate such analyses of bacteria causing human infection. We developed methods to evaluate the mRNA transcript signature of S. aureus in pediatric skin and soft tissue infections (SSTI) directly ex vivo Abscess drainage from 47 healthy pediatric patients undergoing drainage of a soft tissue infection was collected, and RNA was extracted from samples from patients with microbiologically confirmed S. aureus abscesses (42% due to methicillin-resistant S. aureus [MRSA]). Using the NanoString platform and primers targeting S. aureus mRNA transcripts encoding surface-expressed or secreted proteins, we measured direct counts of 188 S. aureus mRNA transcripts in abscess drainage. We further evaluated this mRNA signature in murine models of S. aureus SSTI and nasal colonization where the kinetics of the transcriptome could be determined. Heat maps of the S. aureus mRNA signatures from pediatric abscesses demonstrated consistent per-target expression across patients. While there was significant overlap with the profiles from murine SSTI and nasal colonization, important differences were noted, which can inform efforts to develop therapeutic and vaccine approaches.

Clinical features and outcomes of spitzoid proliferations in children and adolescents.

BACKGROUND: Spitzoid proliferations range from Spitz naevi to melanomas. There are few studies describing clinical features and outcomes in the paediatric population. OBJECTIVES: To determine the clinical features and outcomes of a large paediatric cohort with histopathologically confirmed Spitz tumours. METHODS: This was a retrospective cohort study of patients seen at Boston Children's Hospital who were aged < 20 years and had a histopathological diagnosis of spitzoid proliferation from 1 January 1994 to 23 October 2012. RESULTS: In total 595 patients with 622 spitzoid proliferations were identified (median age 7·4 years, interquartile range 4·6-11·7). Overall 512 proliferations (82·3%) were typical, 107 (17·2.%) were atypical and three (0·5%) were melanomas. The median ages at biopsy were 7·4, 7·2 and 17·2 years, respectively, and there was a significant difference in age at biopsy for patients with typical or atypical proliferations vs. melanoma (P < 0·01). Among samples with positive margins (n = 153), 55% (54 of 98) of typical proliferations, 77% (41 of 53) of atypical proliferations and 100% (two of two) of melanomas were re-excised. Six patients had sentinel lymph node biopsy performed, with three patients demonstrating nodes positive for melanocytic cells. Within a median follow-up of 4·1 years for the full cohort there were no related deaths. CONCLUSIONS: Spitz tumours have strikingly benign outcomes in the paediatric population, although this study is limited by the low number of melanomas and restriction to a single paediatric institution. Aggressive management recommendations should be reconsidered for children and adolescents with banal-appearing Spitz naevi, based on the clinically indolent behaviour in this cohort.

Automated Processing of Dynamic Contrast-Enhanced MRI: Correlation of Advanced Pharmacokinetic Metrics with Tumor Grade in Pediatric Brain Tumors.

BACKGROUND AND PURPOSE: Pharmacokinetic parameters from dynamic contrast-enhanced MR imaging have proved useful for differentiating brain tumor grades in adults. In this study, we retrospectively reviewed dynamic contrast-enhanced perfusion data from children with newly diagnosed brain tumors and analyzed the pharmacokinetic parameters correlating with tumor grade. MATERIALS AND METHODS: Dynamic contrast-enhanced MR imaging data from 38 patients were analyzed by using commercially available software. Subjects were categorized into 2 groups based on pathologic analyses consisting of low-grade (World Health Organization I and II) and high-grade (World Health Organization III and IV) tumors. Pharmacokinetic parameters were compared between the 2 groups by using linear regression models. For parameters that were statistically distinct between the 2 groups, sensitivity and specificity were also estimated. RESULTS: Eighteen tumors were classified as low-grade, and 20, as high-grade. Transfer constant from the blood plasma into the extracellular extravascular space (Ktrans), rate constant from extracellular extravascular space back into blood plasma (Kep), and extracellular extravascular volume fraction (Ve) were all significantly correlated with tumor grade; high-grade tumors showed higher Ktrans, higher Kep, and lower Ve. Although all 3 parameters had high specificity (range, 82%-100%), Kep had the highest specificity for both grades. Optimal sensitivity was achieved for Ve, with a combined sensitivity of 76% (compared with 71% for Ktrans and Kep). CONCLUSIONS: Pharmacokinetic parameters derived from dynamic contrast-enhanced MR imaging can effectively discriminate low- and high-grade pediatric brain tumors.

Neurointerventions in children: radiation exposure and its import.

BACKGROUND AND PURPOSE: Neurointerventions in children have dramatically improved the clinical outlook for patients with previously intractable cerebrovascular conditions, such as vein of Galen malformations and complex arteriovenous fistulas. However, these complex and sometimes lengthy procedures are performed under fluoroscopic guidance and thus unavoidably expose vulnerable pediatric patients to the effects of ionizing radiation. Recent epidemiologic evidence from a national registry of children who underwent CT scans suggests a higher-than-expected incidence of secondary tumors. We sought to calculate the predicted risk of secondary tumors in a large cohort of pediatric neurointerventional patients. MATERIALS AND METHODS: We reviewed our cohort of pediatric neurointerventions, tabulated radiation dose delivered to the skin, and calculated the range of likely brain-absorbed doses by use of previously developed mathematical models. The predicted risk of secondary tumor development as a function of brain-absorbed dose in this cohort was then generated by use of the head CT registry findings. RESULTS: Maximal skin dose and brain-absorbed doses in our cohort were substantially lower than have been previously described. However, we found 1) a statistically significant correlation between radiation dose and age at procedure, as well as number and type of procedures, and 2) a substantial increase in lifetime predicted risk of tumor above baseline in the cohort of young children who undergo neurointerventions. CONCLUSIONS: Although neurointerventional procedures have dramatically improved the prognosis of children facing serious cerebrovascular conditions, the predicted risk of secondary tumors, particularly in the youngest patients and those undergoing multiple procedures, is sobering.

Acoustically derived ice-fracture velocity in central Arctic pack ice.

Sounds radiated by fractures in Arctic ice (called acoustic events) are used to estimate fracture velocity. Both speed and orientation are obtained by measuring Doppler shifts induced by source motion. Data from the SIMI experiment of 1994 in the central Arctic are used in the frequency window 10 to 350 Hz. The estimation procedure assumes that each fracture propagates unilaterally, i.e., unidirectionally. Results for a population of 186 events show fracture propagation speed to be mostly subsonic, in the range 100 to 1100 m/s, significantly lower than the Rayleigh wave speed (1700 m/s for sea ice) assumed in previous studies. The wide range of speeds observed indicates either the presence of distinct multiple fractures in each event, or of a single mechanism at different stages in its propagation.