Sequential tumor molecular profiling identifies likely germline variants.

PURPOSE: To identify likely germline DNA variants from sequential tumor profiling data from hematopoietic malignancies (HMs). METHODS: The coefficient of variance was calculated from variant allele frequency of next-generation sequencing assays. Variants' likelihood of being germline was ranked on a 1 to 5 scale. Outcomes were examined in patients with such variants. RESULTS: In a pilot set of 33 genes, 89% of grade 1, 77% of grade 2, 62% of grade 3, 52% of grade 4, and 21% of grade 5 variants were confirmed to be germline. Among those, 22% were pathogenic or likely pathogenic in genes recognized as conferring hereditary HM risk, including BRCA1/2, CHEK2, CSF3R, and DDX41. To determine if this approach identified genes with known autosomal dominant inheritance, we analyzed sequential data from 1336 genes in 1135 HM patients. Among unique variants, 16% occurred in hereditary HM genes, and 15% were deleterious. Patients with grade 1/2 alleles had decreased survival 2 years after initial molecular testing (78% versus 88%, P = .0037) and increased all-cause mortality compared with those without (hazard ratio 2.02, 95% CI 1.18-3.46, P = .019). CONCLUSION: Variant germline status may be predicted using sequential tumor profiling and patients with likely germline variants experience inferior outcomes compared with those without.

Children with Warts: A Retrospective Study in an Outpatient Setting.

BACKGROUND: The purpose is to investigate the demographics and course of common warts in children in an outpatient setting. METHODS: A retrospective medical chart review and telephone survey study were completed on an outpatient cohort of children (0-17 yrs) with a clinical diagnosis of warts at a single-center, university-based pediatric dermatology practice. The main outcome measures included management, time to resolution, and associated factors of warts in children. RESULTS: Of the 254 patients we contacted, 214 agreed to participate in the survey. The most commonly involved sites were the hands and the head and neck area. Most children received some form of therapy, but it is unclear that any form of treatment altered the course. However, children with a medical history of childhood infections or more than one anatomic site had significantly greater risk of having a longer time to resolution. CONCLUSION: Warts resolved in 65% of children by 2 years and in 80% within 4 years, regardless of treatment. With the exception of a history of childhood infections and having more than one anatomic site, time to resolution was not altered by wart or patient characteristics. Thus counseling without aggressive destructive treatment is a reasonable approach to managing warts in most children. Our findings will provide guidance in the process of shared decision making with parents and children.

Molluscum contagiosum: to treat or not to treat? Experience with 170 children in an outpatient clinic setting in the northeastern United States.

Despite the high prevalence of molluscum contagiosum (MC) in children, epidemiologic data on this common self-limited viral infection is limited. In this report we review our experience with the demographic characteristics, clinical characteristics, management, and time to resolution of MC in 170 children. A retrospective medical chart review and telephone survey were conducted on children younger than 16 years of age evaluated for MC in the Division of Pediatric Dermatology at the Johns Hopkins Children's Center, Baltimore, Maryland, from January 1, 2008, to December 31, 2011. Of 170 children with MC, 51.8% were female and 77.1% were Caucasian. The median age at diagnosis was 5 years and 46.5% had a history of atopic dermatitis (AD). Children with AD had significantly more MC lesions than those without (p < 0.05); 72.9% of children did not receive any treatment. MC lesions completely cleared within 12 months in 45.6% of treated and 48.4% of untreated children and within 18 months in 69.5% of treated and 72.6% of untreated children. Treatment (if any), sex, race, diagnosing physician, number of lesions at diagnosis, number of anatomic locations, or history of AD did not predict time to resolution of MC lesions. MC lesions completely resolved in approximately 50% of children within 12 months and in 70% within 18 months. Treatment did not shorten the time to resolution.

Mechanism of injury predicts case fatality and functional outcomes in pediatric trauma patients: the case for its use in trauma outcomes studies.

BACKGROUND/PURPOSE: The mechanism of injury (MOI) may serve as a useful adjunct to injury scoring systems in pediatric trauma outcomes research. The objective is to determine the independent effect of MOI on case fatality and functional outcomes in pediatric trauma patients. METHODS: Retrospective review of pediatric patients ages 2 to 18 years in the National Trauma Data Bank from 2002 through 2006 was done. Mechanism of injury was classified by the International Classification of Diseases, Ninth Revision, E codes. The main outcome measures were mortality, discharge disposition (home vs rehabilitation setting), and functional impairment at hospital discharge. Multiple logistic regression was used to adjust for injury severity (using the Injury Severity Score and the presence of shock upon admission in the emergency department), age, sex, and severe head or extremity injury. RESULTS: Thirty-five thousand ninety-seven pediatric patients in the National Trauma Data Bank met inclusion criteria. Each MOI had differences in the adjusted odds of death or functional disabilities as compared with the reference group (fall). The MOI with the greatest risk of death was gunshot wounds (odds ratio [OR], 3.52; 95% confidence interval [CI], 2.23-5.54 95). Pediatric pedestrians struck by a motor vehicle have the highest risk of locomotion (OR, 3.30; 95% CI, 2.89-3.77) and expression (OR, 1.65; 95% CI, 1.22-2.23) disabilities. CONCLUSION: Mechanism of injury is a significant predictor of clinical and functional outcomes at discharge for equivalently injured patients. These findings have implications for injury prevention, staging, and prognosis of traumatic injury and posttreatment planning.