Monroe Carell Jr. Children's Hospital

OBJECTIVE: Traumatic brain injury (TBI)-the "silent epidemic"-contributes to worldwide death and disability more than any other traumatic insult. Yet, TBI incidence and distribution across regions and socioeconomic divides remain unknown. In an effort to promote advocacy, understanding, and targeted intervention, the authors sought to quantify the case burden of TBI across World Health Organization (WHO) regions and World Bank (WB) income groups. METHODS: Open-source epidemiological data on road traffic injuries (RTIs) were used to model the incidence of TBI using literature-derived ratios. First, a systematic review on the proportion of RTIs resulting in TBI was conducted, and a meta-analysis of study-derived proportions was performed. Next, a separate systematic review identified primary source studies describing mechanisms of injury contributing to TBI, and an additional meta-analysis yielded a proportion of TBI that is secondary to the mechanism of RTI. Then, the incidence of RTI as published by the Global Burden of Disease Study 2015 was applied to these two ratios to generate the incidence and estimated case volume of TBI for each WHO region and WB income group. RESULTS: Relevant articles and registries were identified via systematic review; study quality was higher in the high-income countries (HICs) than in the low- and middle-income countries (LMICs). Sixty-nine million (95% CI 64-74 million) individuals worldwide are estimated to sustain a TBI each year. The proportion of TBIs resulting from road traffic collisions was greatest in Africa and Southeast Asia (both 56%) and lowest in North America (25%). The incidence of RTI was similar in Southeast Asia (1.5% of the population per year) and Europe (1.2%). The overall incidence of TBI per 100,000 people was greatest in North America (1299 cases, 95% CI 650-1947) and Europe (1012 cases, 95% CI 911-1113) and least in Africa (801 cases, 95% CI 732-871) and the Eastern Mediterranean (897 cases, 95% CI 771-1023). The LMICs experience nearly 3 times more cases of TBI proportionally than HICs. CONCLUSIONS: Sixty-nine million (95% CI 64-74 million) individuals are estimated to suffer TBI from all causes each year, with the Southeast Asian and Western Pacific regions experiencing the greatest overall burden of disease. Head injury following road traffic collision is more common in LMICs, and the proportion of TBIs secondary to road traffic collision is likewise greatest in these countries. Meanwhile, the estimated incidence of TBI is highest in regions with higher-quality data, specifically in North America and Europe.

BACKGROUND: Incidence estimates of hospitalizations for community-acquired pneumonia among children in the United States that are based on prospective data collection are limited. Updated estimates of pneumonia that has been confirmed radiographically and with the use of current laboratory diagnostic tests are needed. METHODS: We conducted active population-based surveillance for community-acquired pneumonia requiring hospitalization among children younger than 18 years of age in three hospitals in Memphis, Nashville, and Salt Lake City. We excluded children with recent hospitalization or severe immunosuppression. Blood and respiratory specimens were systematically collected for pathogen detection with the use of multiple methods. Chest radiographs were reviewed independently by study radiologists. RESULTS: From January 2010 through June 2012, we enrolled 2638 of 3803 eligible children (69%), 2358 of whom (89%) had radiographic evidence of pneumonia. The median age of the children was 2 years (interquartile range, 1 to 6); 497 of 2358 children (21%) required intensive care, and 3 (<1%) died. Among 2222 children with radiographic evidence of pneumonia and with specimens available for bacterial and viral testing, a viral or bacterial pathogen was detected in 1802 (81%), one or more viruses in 1472 (66%), bacteria in 175 (8%), and both bacterial and viral pathogens in 155 (7%). The annual incidence of pneumonia was 15.7 cases per 10,000 children (95% confidence interval [CI], 14.9 to 16.5), with the highest rate among children younger than 2 years of age (62.2 cases per 10,000 children; 95% CI, 57.6 to 67.1). Respiratory syncytial virus was more common among children younger than 5 years of age than among older children (37% vs. 8%), as were adenovirus (15% vs. 3%) and human metapneumovirus (15% vs. 8%). Mycoplasma pneumoniae was more common among children 5 years of age or older than among younger children (19% vs. 3%). CONCLUSIONS: The burden of hospitalization for children with community-acquired pneumonia was highest among the very young, with respiratory viruses the most commonly detected causes of pneumonia. (Funded by the Influenza Division of the National Center for Immunization and Respiratory Diseases.).

IMPORTANCE: Exposure of young animals to commonly used anesthetics causes neurotoxicity including impaired neurocognitive function and abnormal behavior. The potential neurocognitive and behavioral effects of anesthesia exposure in young children are thus important to understand. OBJECTIVE: To examine if a single anesthesia exposure in otherwise healthy young children was associated with impaired neurocognitive development and abnormal behavior in later childhood. DESIGN, SETTING, AND PARTICIPANTS: Sibling-matched cohort study conducted between May 2009 and April 2015 at 4 university-based US pediatric tertiary care hospitals. The study cohort included sibling pairs within 36 months in age and currently 8 to 15 years old. The exposed siblings were healthy at surgery/anesthesia. Neurocognitive and behavior outcomes were prospectively assessed with retrospectively documented anesthesia exposure data. EXPOSURES: A single exposure to general anesthesia during inguinal hernia surgery in the exposed sibling and no anesthesia exposure in the unexposed sibling, before age 36 months. MAIN OUTCOMES AND MEASURES: The primary outcome was global cognitive function (IQ). Secondary outcomes included domain-specific neurocognitive functions and behavior. A detailed neuropsychological battery assessed IQ and domain-specific neurocognitive functions. Parents completed validated, standardized reports of behavior. RESULTS: Among the 105 sibling pairs, the exposed siblings (mean age, 17.3 months at surgery/anesthesia; 9.5% female) and the unexposed siblings (44% female) had IQ testing at mean ages of 10.6 and 10.9 years, respectively. All exposed children received inhaled anesthetic agents, and anesthesia duration ranged from 20 to 240 minutes, with a median duration of 80 minutes. Mean IQ scores between exposed siblings (scores: full scale = 111; performance = 108; verbal = 111) and unexposed siblings (scores: full scale = 111; performance = 107; verbal = 111) were not statistically significantly different. Differences in mean IQ scores between sibling pairs were: full scale = -0.2 (95% CI, -2.6 to 2.9); performance = 0.5 (95% CI, -2.7 to 3.7); and verbal = -0.5 (95% CI, -3.2 to 2.2). No statistically significant differences in mean scores were found between sibling pairs in memory/learning, motor/processing speed, visuospatial function, attention, executive function, language, or behavior. CONCLUSIONS AND RELEVANCE: Among healthy children with a single anesthesia exposure before age 36 months, compared with healthy siblings with no anesthesia exposure, there were no statistically significant differences in IQ scores in later childhood. Further study of repeated exposure, prolonged exposure, and vulnerable subgroups is needed.

The world's preterm birth rate continues to increase. In 2006, preterm births accounted for 12.8% of live births in the United States. Only about half the cases of prematurity result from identifiable causes. This review discusses the challenge of understanding the causes of premature birth and finding ways to prevent it.

This international consensus statement is the collaborative effort of three medical societies representing electrophysiology in North America, Europe, and Asian-Pacific area: the Heart Rhythm Society (HRS), the European Heart Rhythm Association (EHRA), and the Asia Pacific Heart Rhythm Society. The objective of the consensus document is to provide clinical guidance for diagnosis, risk stratification, and management of patients affected by inherited primary arrhythmia syndromes. It summarizes the opinion of the international writing group members based on their own experience and on a general review of the literature with respect to the clinical data on patients affected by channelopathies. This document does not address the indications of genetic testing in patients affected by inherited arrhythmias and their family members. Diagnostic, prognostic, and therapeutic implications of the results of genetic testing are also not included in this document because this topic has been covered by a recent publication1 coauthored by some of the contributors of this consensus document, and it remains the reference text on this topic. Guidance for the evaluation of patients with idiopathic ventricular fibrillation, sudden arrhythmic death …

BACKGROUND: Deletion and the reciprocal duplication in 16p11.2 were recently associated with autism and developmental delay. METHOD: We indentified 27 deletions and 18 duplications of 16p11.2 were identified in 0.6% of all samples submitted for clinical array-CGH (comparative genomic hybridisation) analysis. Detailed molecular and phenotypic characterisations were performed on 17 deletion subjects and ten subjects with the duplication. RESULTS: The most common clinical manifestations in 17 deletion and 10 duplication subjects were speech/language delay and cognitive impairment. Other phenotypes in the deletion patients included motor delay (50%), seizures ( approximately 40%), behavioural problems ( approximately 40%), congenital anomalies ( approximately 30%), and autism ( approximately 20%). The phenotypes among duplication patients included motor delay (6/10), behavioural problems (especially attention deficit hyperactivity disorder (ADHD)) (6/10), congenital anomalies (5/10), and seizures (3/10). Patients with the 16p11.2 deletion had statistically significant macrocephaly (p<0.0017) and 6 of the 10 patients with the duplication had microcephaly. One subject with the deletion was asymptomatic and another with the duplication had a normal cognitive and behavioural phenotype. Genomic analyses revealed additional complexity to the 16p11.2 region with mechanistic implications. The chromosomal rearrangement was de novo in all but 2 of the 10 deletion cases in which parental studies were available. Additionally, 2 de novo cases were apparently mosaic for the deletion in the analysed blood sample. Three de novo and 2 inherited cases were observed in the 5 of 10 duplication patients where data were available. CONCLUSIONS: Recurrent reciprocal 16p11.2 deletion and duplication are characterised by a spectrum of primarily neurocognitive phenotypes that are subject to incomplete penetrance and variable expressivity. The autism and macrocephaly observed with deletion and ADHD and microcephaly seen in duplication patients support a diametric model of autism spectrum and psychotic spectrum behavioural phenotypes in genomic sister disorders.

BACKGROUND: Hypophosphatasia results from mutations in the gene for the tissue-nonspecific isozyme of alkaline phosphatase (TNSALP). Inorganic pyrophosphate accumulates extracellularly, leading to rickets or osteomalacia. Severely affected babies often die from respiratory insufficiency due to progressive chest deformity or have persistent bone disease. There is no approved medical therapy. ENB-0040 is a bone-targeted, recombinant human TNSALP that prevents the manifestations of hypophosphatasia in Tnsalp knockout mice. METHODS: We enrolled infants and young children with life-threatening or debilitating perinatal or infantile hypophosphatasia in a multinational, open-label study of treatment with ENB-0040. The primary objective was the healing of rickets, as assessed by means of radiographic scales. Motor and cognitive development, respiratory function, and safety were evaluated, as well as the pharmacokinetics and pharmacodynamics of ENB-0040. RESULTS: Of the 11 patients recruited, 10 completed 6 months of therapy; 9 completed 1 year. Healing of rickets at 6 months in 9 patients was accompanied by improvement in developmental milestones and pulmonary function. Elevated plasma levels of the TNSALP substrates inorganic pyrophosphate and pyridoxal 5'-phosphate diminished. Increases in serum parathyroid hormone accompanied skeletal healing, often necessitating dietary calcium supplementation. There was no evidence of hypocalcemia, ectopic calcification, or definite drug-related serious adverse events. Low titers of anti-ENB-0040 antibodies developed in four patients, with no evident clinical, biochemical, or autoimmune abnormalities at 48 weeks of treatment. CONCLUSIONS: ENB-0040, an enzyme-replacement therapy, was associated with improved findings on skeletal radiographs and improved pulmonary and physical function in infants and young children with life-threatening hypophosphatasia. (Funded by Enobia Pharma and Shriners Hospitals for Children; ClinicalTrials.gov number, NCT00744042.).

<b>The GINA Strategy Report provides clinicians with an annually updated evidence-based strategy for asthma management and prevention. This article summarizes key recommendations from GINA 2021, and the evidence underpinning the new changes.</b>https://bit.ly/3FZblIS

STUDY OBJECTIVES: To relate parentally reported sleep concerns in autism spectrum disorders (ASD) to polysomnographic (PSG) findings and measures of daytime behavior and autism symptomatology. DESIGN: Cross-sectional study involving validated questionnaires, sleep histories and diaries, 2 nights of PSG, and the Autism Diagnostic Observation Schedule (ADOS). SETTING: Vanderbilt University General Clinical Research Center Sleep Core. PARTICIPANTS: 21 children with ASD and 10 typically developing (TD) children, aged 4-10 years. Children were free of psychotropic medications, with no history of mental retardation or epileptic seizures. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: Children with ASD were defined as "good sleepers" (10 children) and "poor sleepers" (11 children) on the basis of parental report; the age-comparable TD children were all reported by their parents to be good sleepers. Poor sleepers with ASD showed prolonged sleep latency and decreased sleep efficiency on night 1 of PSG and differed on insomnia-related subscales of the Children's Sleep Habits Questionnaire (CSHQ; increased sleep onset delay and decreased sleep duration). The good sleepers with ASD did not differ from the TD children in sleep architecture or on CSHQ domains. As compared with ASD good sleepers, the ASD poor sleepers also had higher scores related to affective problems on the Child Behavior Checklist and more problems with reciprocal social interaction on the ADOS. CONCLUSIONS: Parentally reported sleep concerns of insomnia in children with ASD are substantiated by validated sleep questionnaires and by PSG. Furthermore, good sleepers with ASD showed fewer affective problems and better social interactions than ASD poor sleepers.

The Ovarian-Adnexal Reporting and Data System (O-RADS) US risk stratification and management system is designed to provide consistent interpretations, to decrease or eliminate ambiguity in US reports resulting in a higher probability of accuracy in assigning risk of malignancy to ovarian and other adnexal masses, and to provide a management recommendation for each risk category. It was developed by an international multidisciplinary committee sponsored by the American College of Radiology and applies the standardized reporting tool for US based on the 2018 published lexicon of the O-RADS US working group. For risk stratification, the O-RADS US system recommends six categories (O-RADS 0-5), incorporating the range of normal to high risk of malignancy. This unique system represents a collaboration between the pattern-based approach commonly used in North America and the widely used, European-based, algorithmic-style International Ovarian Tumor Analysis (IOTA) Assessment of Different Neoplasias in the Adnexa model system, a risk prediction model that has undergone successful prospective and external validation. The pattern approach relies on a subgroup of the most predictive descriptors in the lexicon based on a retrospective review of evidence prospectively obtained in the IOTA phase 1-3 prospective studies and other supporting studies that assist in differentiating management schemes in a variety of almost certainly benign lesions. With O-RADS US working group consensus, guidelines for management in the different risk categories are proposed. Both systems have been stratified to reach the same risk categories and management strategies regardless of which is initially used. At this time, O-RADS US is the only lexicon and classification system that encompasses all risk categories with their associated management schemes.

PURPOSE: To evaluate the DSM-5 diagnosis of Avoidant/Restrictive Food Intake Disorder (ARFID) in children and adolescents with poor eating not associated with body image concerns. METHODS: A retrospective case-control study of 8-18-year-olds, using a diagnostic algorithm, compared all cases with ARFID presenting to seven adolescent-medicine eating disorder programs in 2010 to a randomly selected sample with anorexia nervosa (AN) and bulimia nervosa (BN). Demographic and clinical information were recorded. RESULTS: Of 712 individuals studied, 98 (13.8%) met ARFID criteria. Patients with ARFID were younger than those with AN (n = 98) or BN (n = 66), (12.9 vs. 15.6 vs. 16.5 years), had longer durations of illness (33.3 vs. 14.5 vs. 23.5 months), were more likely to be male (29% vs. 15% vs. 6%), and had a percent median body weight intermediate between those with AN or BN (86.5 vs. 81.0 and 107.5). Patients with ARFID included those with selective (picky) eating since early childhood (28.7%); generalized anxiety (21.4%); gastrointestinal symptoms (19.4%); a history of vomiting/choking (13.2%); and food allergies (4.1%). Patients with ARFID were more likely to have a comorbid medical condition (55% vs. 10% vs. 11%) or anxiety disorder (58% vs. 35% vs. 33%) and were less likely to have a mood disorder (19% vs. 31% vs. 58%). CONCLUSIONS: Patients with ARFID were demographically and clinically distinct from those with AN or BN. They were significantly underweight with a longer duration of illness and had a greater likelihood of comorbid medical and/or psychiatric symptoms.

OBJECTIVES: Suicide ideation (SI) and suicide attempts (SAs) have been reported as increasing among US children over the last decade. We examined trends in emergency and inpatient encounters for SI and SA at US children's hospitals from 2008 to 2015. METHODS: We used retrospective analysis of administrative billing data from the Pediatric Health Information System database. RESULTS: There were 115 856 SI and SA encounters during the study period. Annual percentage of all visits for SI and SA almost doubled, increasing from 0.66% in 2008 to 1.82% in 2015 (average annual increase 0.16 percentage points [95% confidence intervals (CIs) 0.15 to 0.17]). Significant increases were noted in all age groups but were higher in adolescents 15 to 17 years old (average annual increase 0.27 percentage points [95% CI 0.23 to 0.30]) and adolescents 12 to 14 years old (average annual increase 0.25 percentage points [95% CI 0.21 to 0.27]). Increases were noted in girls (average annual increase 0.14 percentage points [95% CI 0.13 to 0.15]) and boys (average annual increase 0.10 percentage points [95% CI 0.09 to 0.11]), but were higher for girls. Seasonal variation was also observed, with the lowest percentage of cases occurring during the summer and the highest during spring and fall. CONCLUSIONS: Encounters for SI and SA at US children's hospitals increased steadily from 2008 to 2015 and accounted for an increasing percentage of all hospital encounters. Increases were noted across all age groups, with consistent seasonal patterns that persisted over the study period. The growing impact of pediatric mental health disorders has important implications for children's hospitals and health care delivery systems.

OBJECTIVE: Medication errors are a major concern of health care professionals and medical institutions, especially errors involving children. Studies in adults have shown that computerized physician order entry (CPOE) systems reduce medication errors and adverse drug events (ADEs). The effect of CPOE implementation in a pediatric population has not been reported. The objective of this study was to evaluate the impact of CPOE on the frequency of errors in the medication ordering process in a pediatric critical care unit (PCCU). METHODS: A prospective trial was conducted of 514 pediatric patients who were admitted to a 20-bed PCCU in a tertiary-care children's hospital before and after implementation of CPOE. Medication errors were identified after review of all orders during the study period and then further classified as potential ADEs, medication prescribing errors (MPE), and rule violations (RV). RESULTS: A total of 13 828 medication orders were reviewed. Before implementation, potential ADEs occurred at a rate of 2.2 per 100 orders, MPEs at a rate of 30.1 per 100 orders, and RVs at a rate of 6.8 per 100 orders. After implementation, the rate of potential ADEs was reduced to 1.3 per 100 orders, MPEs to 0.2 per 100 orders, and RVs to 0.1 per 100 orders. The overall error reduction was 95.9%. Potential ADEs were reduced by 40.9%, and MPEs and RVs were reduced by 99.4% and 97.9%, respectively. CONCLUSIONS: The implementation of CPOE resulted in almost a complete elimination of MPEs and RVs and a significant but less dramatic effect on potential ADEs.

BACKGROUND: The adverse effects of excess alcohol intake on cognitive function are well established, but the effect of moderate consumption is uncertain. METHODS: Between 1995 and 2001, we evaluated cognitive function in 12,480 participants in the Nurses' Health Study who were 70 to 81 years old, with follow-up assessments in 11,102 two years later. The level of alcohol consumption was ascertained regularly beginning in 1980. We calculated multivariate-adjusted mean cognitive scores and multivariate-adjusted risks of cognitive impairment (defined as the lowest 10 percent of the scores) and a substantial decline in cognitive function over time (defined as a change that was in the worst 10 percent of the distribution of the decline). We also stratified analyses according to the apolipoprotein E genotype in a subgroup of women. RESULTS: After multivariate adjustment, moderate drinkers (those who consumed less than 15.0 g of alcohol per day [about one drink]) had better mean cognitive scores than nondrinkers. Among moderate drinkers, as compared with nondrinkers, the relative risk of impairment was 0.77 on our test of general cognition (95 percent confidence interval, 0.67 to 0.88) and 0.81 on the basis of a global cognitive score combining the results of all tests (95 percent confidence interval, 0.70 to 0.93). The results for cognitive decline were similar; for example, on our test of general cognition, the relative risk of a substantial decline in performance over a two-year period was 0.85 (95 percent confidence interval, 0.74 to 0.98) among moderate drinkers, as compared with nondrinkers. There were no significant associations between higher levels of drinking (15.0 to 30.0 g per day) and the risk of cognitive impairment or decline. There were no significant differences in risks according to the beverage (e.g., wine or beer) and no interaction with the apolipoprotein E genotype. CONCLUSIONS: Our data suggest that in women, up to one drink per day does not impair cognitive function and may actually decrease the risk of cognitive decline.

PURPOSE: Current American Urological Association treatment guidelines for vesicoureteral reflux do not include any recommendations pertaining to endoscopic therapy (subureteral injection of bulking agent). We performed a meta-analysis of the existing literature pertaining to endoscopic treatment to allow comparison with reports of open surgical correction. MATERIALS AND METHODS: We searched all peer reviewed articles published through 2003 pertaining to endoscopic treatment of vesicoureteral reflux. A total of 63 articles were double reviewed by 9 pediatric urologists, and the data were tabulated on data retrieval sheets. A mixed effects logistic regression model was used to obtain overall estimates of event probabilities (eg reflux resolution, ureteral obstruction) together with their 95% confidence intervals. Individual study estimates were obtained with overall estimate and observation characteristics using empirical Bayes calculations. Differences between or among specific groups were assessed using the F-test. RESULTS: The database included 5,527 patients and 8,101 renal units. Following 1 treatment the reflux resolution rate (by ureter) for grades I and II reflux was 78.5%, grade III 72%, grade IV 63% and grade V 51%. If the first injection was unsuccessful, the second treatment had a success rate of 68%, and the third treatment 34%. The aggregate success rate with 1 or more injections was 85%. The success rate was significantly lower for duplicated (50%) vs single systems (73%), and neuropathic (62%) vs normal bladders (74%). The success rate was similar among children and adults. Following a previous failed open reimplantation endoscopic treatment was successful in 65% of patients. After endoscopic treatment with variable followup pyelonephritis developed in 0.75% of patients and cystitis in 6%. There were few reports of renal scarring following treatment. CONCLUSIONS: Endoscopic treatment provides a high rate of success in children with reflux that decreases with increasing grade, although multiple treatments may be necessary. Future reports of endoscopic therapy should include rates of urinary tract infection and renal scarring.

Probiotic bacteria can potentially have beneficial effects on the clinical course of several intestinal disorders, but our understanding of probiotic action is limited. We have identified a probiotic bacteria-derived soluble protein, p40, from Lactobacillus rhamnosus GG (LGG), which prevents cytokine-induced apoptosis in intestinal epithelial cells. In the current study, we analyzed the mechanisms by which p40 regulates cellular responses in intestinal epithelial cells and p40's effects on experimental colitis using mouse models. We show that the recombinant p40 protein activated EGFR, leading to Akt activation. Activation of EGFR by p40 was required for inhibition of cytokine-induced apoptosis in intestinal epithelial cells in vitro and ex vivo. Furthermore, we developed a pectin/zein hydrogel bead system to specifically deliver p40 to the mouse colon, which activated EGFR in colon epithelial cells. Administration of p40-containing beads reduced intestinal epithelial apoptosis and disruption of barrier function in the colon epithelium in an EGFR-dependent manner, thereby preventing and treating DSS-induced intestinal injury and acute colitis. Furthermore, p40 activation of EGFR was required for ameliorating colon epithelial cell apoptosis and chronic inflammation in oxazolone-induced colitis. These data define what we believe to be a previously unrecognized mechanism of probiotic-derived soluble proteins in protecting the intestine from injury and inflammation.

Phospholipid bilayers that constitute endo-lysosomal vesicles can pose a barrier to delivery of biologic drugs to intracellular targets. To overcome this barrier, a number of synthetic drug carriers have been engineered to actively disrupt the endosomal membrane and deliver cargo into the cytoplasm. Here, we describe the hemolysis assay, which can be used as rapid, high-throughput screen for the cytocompatibility and endosomolytic activity of intracellular drug delivery systems. In the hemolysis assay, human red blood cells and test materials are co-incubated in buffers at defined pHs that mimic extracellular, early endosomal, and late endo-lysosomal environments. Following a centrifugation step to pellet intact red blood cells, the amount of hemoglobin released into the medium is spectrophotometrically measured (405 nm for best dynamic range). The percent red blood cell disruption is then quantified relative to positive control samples lysed with a detergent. In this model system the erythrocyte membrane serves as a surrogate for the lipid bilayer membrane that enclose endo-lysosomal vesicles. The desired result is negligible hemolysis at physiologic pH (7.4) and robust hemolysis in the endo-lysosomal pH range from approximately pH 5-6.8.

Background: The epidemiology of Mycoplasma pneumoniae (Mp) among US children (<18 years) hospitalized with community-acquired pneumonia (CAP) is poorly understood. Methods: In the Etiology of Pneumonia in the Community study, we prospectively enrolled 2254 children hospitalized with radiographically confirmed pneumonia from January 2010-June 2012 and tested nasopharyngeal/oropharyngeal swabs for Mp using real-time polymerase chain reaction (PCR). Clinical and epidemiological features of Mp PCR-positive and -negative children were compared using logistic regression. Macrolide susceptibility was assessed by genotyping isolates. Results: One hundred and eighty two (8%) children were Mp PCR-positive (median age, 7 years); 12% required intensive care and 26% had pleural effusion. No in-hospital deaths occurred. Macrolide resistance was found in 4% (6/169) isolates. Of 178 (98%) Mp PCR-positive children tested for copathogens, 50 (28%) had ≥1 copathogen detected. Variables significantly associated with higher odds of Mp detection included age (10-17 years: adjusted odds ratio [aOR], 10.7 [95% confidence interval {CI}, 5.4-21.1] and 5-9 years: aOR, 6.4 [95% CI, 3.4-12.1] vs 2-4 years), outpatient antibiotics ≤5 days preadmission (aOR, 2.3 [95% CI, 1.5-3.5]), and copathogen detection (aOR, 2.1 [95% CI, 1.3-3.3]). Clinical characteristics were non-specific. Conclusions: Usually considered as a mild respiratory infection, Mp was the most commonly detected bacteria among children aged ≥5 years hospitalized with CAP, one-quarter of whom had codetections. Although associated with clinically nonspecific symptoms, there was a need for intensive care in some cases. Mycoplasma pneumoniae should be included in the differential diagnosis for school-aged children hospitalized with CAP.

Cancer may arise from a cancer stem/progenitor cell that shares characteristics with its normal counterpart. We report the reconstitution of the original human prostate cancer specimen from epithelial cell lines (termed HPET for human prostate epithelial/hTERT) derived from this sample. These tumors can be described in terms of Gleason score, a classification not applied to any of the transgenic mouse models currently developed to mimic human disease. Immunohistochemical and Western blot analyses indicate that they do not express androgen receptor or p63, similar to that reported for prostate stem cells. These cell lines also express embryonic stem markers (Oct4, Nanog, and Sox2) as well as early progenitor cell markers (CD44 and Nestin) in vitro. Clonally derived HPET cells reconstitute the original human tumor in vivo and differentiate into the three prostate epithelial cell lineages, indicating that they arise from a common stem/progenitor cell. Serial transplantation experiments reconstitute the tumors, suggesting that a fraction of parental or clonally derived HPET cells have self-renewal potential. Thus, this model may enhance our understanding of human tumor development and provide a mechanism for studying cancer stem/progenitor cells in differentiation, tumorigenesis, preclinical testing, and the development of drug resistance.

Since September 2010, more than 10,000 patients have undergone preemptive, panel-based pharmacogenomic testing through the Vanderbilt Pharmacogenomic Resource for Enhanced Decisions in Care and Treatment program. Analysis of the genetic data from the first 9,589 individuals reveals that the frequency of genetic variants is concordant with published allele frequencies. Based on five currently implemented drug-gene interactions, the multiplexed test identified one or more actionable variants in 91% of the genotyped patients and in 96% of African American patients. Using medication exposure data from electronic medical records, we compared a theoretical "reactive," prescription-triggered, serial single-gene testing strategy with our preemptive, multiplexed genotyping approach. Reactive genotyping would have generated 14,656 genetic tests. These data highlight three advantages of preemptive genotyping: (i) the vast majority of patients carry at least one pharmacogenetic variant; (ii) data are available at the point of care; and (iii) there is a substantial reduction in testing burden compared with a reactive strategy.