A data-driven algorithm integrating clinical and laboratory features for the diagnosis and prognosis of necrotizing enterocolitis.

BACKGROUND: Necrotizing enterocolitis (NEC) is a major source of neonatal morbidity and mortality. Since there is no specific diagnostic test or risk of progression model available for NEC, the diagnosis and outcome prediction of NEC is made on clinical grounds. The objective in this study was to develop and validate new NEC scoring systems for automated staging and prognostic forecasting. STUDY DESIGN: A six-center consortium of university based pediatric teaching hospitals prospectively collected data on infants under suspicion of having NEC over a 7-year period. A database comprised of 520 infants was utilized to develop the NEC diagnostic and prognostic models by dividing the entire dataset into training and testing cohorts of demographically matched subjects. Developed on the training cohort and validated on the blind testing cohort, our multivariate analyses led to NEC scoring metrics integrating clinical data. RESULTS: Machine learning using clinical and laboratory results at the time of clinical presentation led to two nec models: (1) an automated diagnostic classification scheme; (2) a dynamic prognostic method for risk-stratifying patients into low, intermediate and high NEC scores to determine the risk for disease progression. We submit that dynamic risk stratification of infants with NEC will assist clinicians in determining the need for additional diagnostic testing and guide potential therapies in a dynamic manner. ALGORITHM AVAILABILITY: http://translationalmedicine.stanford.edu/cgi-bin/NEC/index.pl and smartphone application upon request.

Urine protein biomarkers for the diagnosis and prognosis of necrotizing enterocolitis in infants.

OBJECTIVES: To test the hypothesis that an exploratory proteomics analysis of urine proteins with subsequent development of validated urine biomarker panels would produce molecular classifiers for both the diagnosis and prognosis of infants with necrotizing enterocolitis (NEC). STUDY DESIGN: Urine samples were collected from 119 premature infants (85 NEC, 17 sepsis, 17 control) at the time of initial clinical concern for disease. The urine from 59 infants was used for candidate biomarker discovery by liquid chromatography/mass spectrometry. The remaining 60 samples were subject to enzyme-linked immunosorbent assay for quantitative biomarker validation. RESULTS: A panel of 7 biomarkers (alpha-2-macroglobulin-like protein 1, cluster of differentiation protein 14, cystatin 3, fibrinogen alpha chain, pigment epithelium-derived factor, retinol binding protein 4, and vasolin) was identified by liquid chromatography/mass spectrometry and subsequently validated by enzyme-linked immunosorbent assay. These proteins were consistently found to be either up- or down-regulated depending on the presence, absence, or severity of disease. Biomarker panel validation resulted in a receiver-operator characteristic area under the curve of 98.2% for NEC vs sepsis and an area under the curve of 98.4% for medical NEC vs surgical NEC. CONCLUSIONS: We identified 7 urine proteins capable of providing highly accurate diagnostic and prognostic information for infants with suspected NEC. This work represents a novel approach to improving the efficiency with which we diagnose early NEC and identify those at risk for developing severe, or surgical, disease.

Traumatic abdominal wall hernias: an emerging trend in handlebar injuries.

Handlebar injuries are well described in pediatric patients and are frequently associated with internal injuries, including the "classic" duodenal hematoma and solid organ injuries. Before this report, traumatic handlebar hernias were considered rare. They occur when the end of the handlebar (often bare or lacking protective equipment) applies a significant force to a focal area of the abdomen leading to a disruption in the underlying muscle fibers and fascia while sparing the overlying skin. Such nonpenetrating injuries may present with subtle clinical signs and should always be considered in the differential diagnosis. Imaging, with the use of computed tomographic scan or ultrasound will confirm the diagnosis as well as identify any associated injuries. The management plan usually requires surgical exploration and repair of the defect. The prognosis is favorable presuming that there is no significant underlying injury. In this report, we present a series of 5 patients with traumatic handlebar hernia-the most frequently-occurring injury in our series-and review concurrent associated injuries.

Novel report of an adrenal adenoma in a newborn.

An adrenal mass in a newborn usually suggests a diagnosis of neuroblastoma or hemorrhage. A 6-week-old girl was referred for evaluation of a left adrenal mass. The initial findings were most consistent with an adrenal hemorrhage. On surveillance imaging, the lesion was characterized as a complex cystic mass. The patient subsequently developed lesions in the right adrenal gland and liver as well as multiple cutaneous lesions. Although the contralateral adrenal and hepatic lesions resolved spontaneously, the left adrenal and cutaneous lesions persisted. Subsequent imaging revealed that the mural components of the left adrenal mass had increased in size, and at age 13 months, a laparoscopic left adrenalectomy was performed. A benign adrenal adenoma with myxoid changes was reported on surgical pathology. This is the first reported case in a newborn.

Results of a longitudinal study of rigorous manuscript submission guidelines designed to improve the quality of clinical research reporting in a peer-reviewed surgical journal.

BACKGROUND/PURPOSE: In an effort to improve the reporting quality of clinical research, the Journal of Pediatric Surgery instituted specific reporting guidelines for authors beginning June 2006. This study was conducted to evaluate whether these guidelines improved reporting of observational studies. METHODS: The Guidelines for the Reporting of Clinical Research Data (Guidelines) included 23 criteria in 3 subcategories: Methods, Results, and More than one treatment group. Reporting quality was evaluated by determining the percentage of criteria met. Seventy-three articles before implementation and 147 articles after implementation were independently assessed by 2 reviewers. RESULTS: Mean global composite scores increased from 72.2 pre-Guidelines to 80.1 post-Guidelines (P < .0001). Scores increased in each subcategory: Methods, 71.9 to 78.6 (P < .0001); Results, 77.2 to 83.0 (P = .002); and More than one treatment group, 40.0 to 70.6 (P = .0003). Post-Guidelines implementation scores have increased over time. CONCLUSIONS: The introduction of the Guidelines resulted in significant improvement in the quality of reporting in the Journal. The low cost vs the benefit suggests that the Guidelines can be an effective way to improve reporting quality in nonrandomized studies. We encourage further efforts to increase inclusion of reporting criteria as well as evaluation and improvement of the Guidelines. We suggest that editors of other surgical publications consider implementing analogous guidelines.

The political path to mandatory prenatal HIV testing in Connecticut.

Editor's note: The study by Simpson and Forsyth published in this issue of JANAC is an evaluation of women's reactions to Connecticut Public Act 99-2, which established mandatory HIV testing for pregnant women in the state. Manuscript reviewers requested further information about the legislation. The authors provide an overview of the legislation in this commentary.

State-mandated HIV testing in Connecticut: personal perspectives of women found to be infected during pregnancy.

In the 5 years after the adoption of state-mandated HIV testing in Connecticut, 33% of HIV-positive pregnant women in the state were newly diagnosed during their pregnancy. Women who first learned that they were HIV-infected during pregnancy comprised of a unique group of people tested, in essence, by state mandate. A total of 11 such women agreed to in-depth interviews to share their personal perspectives regarding the benefits as well as the adverse sequelae of HIV testing for themselves, their children, and the public health. Each woman recalled her initial response to the law, to her HIV diagnosis, and to the seemingly unavoidable challenge to her self-identity and described the ensuing adjustments. There was universal agreement by the study subjects that the law was of overriding and significant benefit.

Promising strategies for preventing perinatal HIV transmission: model programs from three states.

OBJECTIVES: This paper describes and compares three innovative methods for preventing perinatal HIV transmission. Each of these strategies has been developed based on an in-depth assessment of the strengths and weaknesses of existing prevention approaches, and the needs of the populations they serve. METHODS: Florida expanded an existing outreach program to include women in jails in several high-prevalence counties. Incarcerated women were offered testing for pregnancy and HIV and linked to medical and supportive services. One Connecticut hospital sought to increase prenatal HIV testing rates by requiring HIV test results in the electronic medical records. This program is being expanded to other hospitals throughout the state. Louisiana has implemented a systematic review of perinatal data in order to identify potential programmatic enhancements. This review has led to the perinatal fast track system, designed to quickly identify HIV-infected pregnant women and connect them to care. RESULTS: Each program demonstrated improvements in indicators related to prevention of perinatal HIV transmission, such as increased utilization of prenatal care, increased prenatal testing rates, and decreases in perinatal HIV transmission. CONCLUSIONS: These case studies emphasize two key similarities among these programs: the value of collaboration between agencies providing care and services to HIV-infected and high-risk women of childbearing age, and the importance of maximizing opportunities for HIV testing and treatment. These strategies have demonstrated effectiveness in improving health outcomes and reducing perinatal HIV transmission.

Virologic and host characteristics of human immunodeficiency virus type 1-infected pediatric long term survivors.

BACKGROUND: There are limited data concerning determinants of varying clinical progression rates in human immunodeficiency virus type 1 (HIV-1)-infected children. Therefore, we sought to determine whether viral or host factors associated with nonprogressive HIV-1 infection in adults play a role in limiting progression of infection in 5 vertically infected youths, ages 12-18 years, who have displayed no signs of advanced HIV-1 disease or acquired immunodeficiency syndrome despite having received minimal treatment with antiretroviral drugs. RESULTS: The 5 individuals, whom we characterize as long term survivors, have maintained low loads of HIV-1 RNA in plasma when compared to many of their peers, and have also maintained normal and stable CD4 T-lymphocyte numbers and percentages throughout their lives. Determination of their predominant HIV-1 sequences revealed that 4 of 5 patients harbor virus with markers of resistance to their therapy (one was never treated). Furthermore 2 harbored viral isolates that contained insertions in Gag or Vif that inhibit HIV-1 replication. Moreover, 2 were found to be heterozygous for the CCR2 polymorphism 64I, a genotype associated with slower progression to acquired immunodeficiency syndrome in adults. All 5 expressed the histocompatibility leukocyte antigen DQ1 and 2 had unusual DR/DQ1 phenotypes. CONCLUSIONS: We believe that the limited antiretroviral therapy received by the long term survivors cannot solely account for their benign clinical status. Therefore, we conclude that other factors, including gene polymorphisms that affect viral replicative capacity, account for the long term survival in some, and deduce that, as in adults, no single factor (virologic or host) can account for this clinical phenotype in all cases.