Risk Stratification Among Men With Prostate Imaging Reporting and Data System version 2 Category 3 Transition Zone Lesions: Is Biopsy Always Necessary?

OBJECTIVE: The objective of our study was to determine the clinical and MRI characteristics of clinically significant prostate cancer (PCA) (Gleason score ≥ 3 + 4) in men with Prostate Imaging Reporting and Data System version 2 (PI-RADSv2) category 3 transition zone (TZ) lesions. MATERIALS AND METHODS: From 2014 to 2016, 865 men underwent prostate MRI and MRI/ultrasound (US) fusion biopsy (FB). A subset of 90 FB-naïve men with 96 PI-RADSv2 category 3 TZ lesions was identified. Patients were imaged at 3 T using a body coil. Images were assigned a PI-RADSv2 category by an experienced radiologist. Using clinical data and imaging features, we performed univariate and multivariate analyses to identify predictors of clinically significant PCA. RESULTS: The mean patient age was 66 years, and the mean prostate-specific antigen density (PSAD) was 0.13 ng/mL2. PCA was detected in 34 of 96 (35%) lesions, 14 of which (15%) harbored clinically significant PCA. In univariate analysis, DWI score, prostate volume, and PSAD were significant predictors (p < 0.05) of clinically significant PCA with a suggested significance for apparent diffusion coefficient (ADC) and prostate-specific antigen value (p < 0.10). On multivariate analysis, PSAD and lesion ADC were the most important covariates. The combination of both PSAD of 0.15 ng/mL2 or greater and an ADC value of less than 1000 mm2/s yielded an AUC of 0.91 for clinically significant PCA (p < 0.001). If FB had been restricted to these criteria, only 10 of 90 men would have undergone biopsy, resulting in diagnosis of clinically significant PCA in 60% with eight men (9%) misdiagnosed (false-negative). CONCLUSION: The yield of FB in men with PI-RADSv2 category 3 TZ lesions for clinically significant PCA is 15% but significantly improves to 60% (AUC > 0.9) among men with PSAD of 0.15 ng/mL2 or greater and lesion ADC value of less than 1000 mm2/s.

Serial Magnetic Resonance Imaging in Active Surveillance of Prostate Cancer: Incremental Value.

PURPOSE: We assessed whether changes in serial multiparametric magnetic resonance imaging can help predict the pathological progression of prostate cancer in men on active surveillance. MATERIALS AND METHODS: A retrospective cohort study was conducted of 49 consecutive men with Gleason 6 prostate cancer who underwent multiparametric magnetic resonance imaging at baseline and again more than 6 months later, each followed by a targeted prostate biopsy, between January 2011 and May 2015. We evaluated whether progression on multiparametric magnetic resonance imaging (an increase in index lesion suspicion score, increase in index lesion volume or decrease in index lesion apparent diffusion coefficient) could predict pathological progression (Gleason 3 + 4 or greater on subsequent biopsy, in systematic or targeted cores). Diagnostic performance of multiparametric magnetic resonance imaging was determined with and without clinical data using a binary logistic regression model. RESULTS: The mean interval between baseline and followup multiparametric magnetic resonance imaging was 28.3 months (range 11 to 43). Pathological progression occurred in 19 patients (39%). The sensitivity, specificity, positive predictive value and negative predictive value of multiparametric magnetic resonance imaging was 37%, 90%, 69% and 70%, respectively. Area under the receiver operating characteristic curve was 0.63. A logistic regression model using clinical information (maximum cancer core length greater than 3 mm on baseline biopsy or a prostate specific antigen density greater than 0.15 ng/ml(2) at followup biopsy) had an AUC of 0.87 for predicting pathological progression. The addition of serial multiparametric magnetic resonance imaging data significantly improved the AUC to 0.91 (p=0.044). CONCLUSIONS: Serial multiparametric magnetic resonance imaging adds incremental value to prostate specific antigen density and baseline cancer core length for predicting Gleason 6 upgrading in men on active surveillance.

Electrocardiographic consequences of cardiac iron overload in thalassemia major.

Iron cardiomyopathy is a leading cause of death in transfusion-dependent thalassemia major (TM) patients and MRI (T2*) can recognize preclinical cardiac iron overload, but, is unavailable to many centers. We evaluated the ability of 12-lead electrocardiography to predict cardiac iron loading in TM. 12-lead electrocardiogram and cardiac T2* measurements were performed prospectively, with a detectable cardiac iron cutoff of T2*less than 20 ms. Patients with and without cardiac iron were compared using two-sample statistics and against population norms using age and gender-matched Z-scores. 45/78 patients had detectable cardiac iron. Patients having cardiac iron were older and more likely female but had comparable liver iron burdens and serum ferritin. Increased heart rate (HR) and prolonged corrected QT interval (QT(c)) were present, regardless of cardiac iron status. Repolarization abnormalities were the strongest predictors of cardiac iron, including QT/QT(c) prolongation, left shift of T-wave axis, and interpretation of ST/T-wave morphology. Recursive partitioning of the data for females using T-axis and HR and for males using QT, HR, and T-axis produced algorithms with AUROC's of 88.3 and 87.1, respectively. Bradycardia and repolarization abnormalities on 12-lead electrocardiography were the most specific markers for cardiac iron in thalassemia major. Changes in these variables may be helpful to stratify cardiac risk when cardiac MRI is unavailable. However, diagnostic algorithms need to be vetted on larger and more diverse patient populations and longitudinal studies are necessary to determine reversibility of the observed abnormalities.

The impact of hepatic portoenterostomy on liver transplantation for the treatment of biliary atresia: early failure adversely affects outcome.

The most common indication for pediatric LTx is biliary atresia with failed HPE, yet the effect of previous HPE on the outcome after LTx has not been well characterized. We retrospectively reviewed a single-center experience with 134 consecutive pediatric liver transplants for the treatment of biliary atresia from 1 May 1995 to 28 April 2008. Of 134 patients, 22 underwent LTx without prior HPE (NPE), while 112 patients underwent HPE first. HPE patients were grouped into EF, defined as need for LTx within the first year of life, and LF, defined as need for LTx beyond the first year of life. NPE and EF groups differed significantly from the LF group in age, weight, PELD, and ICU status (p < 0.05) with NPE having the highest PELD and ICU status. Patients who underwent salvage LTx after EF following HPE had a significantly higher incidence of post-operative bacteremia and septicemia (p < 0.05), and subsequently lower survival rates. One-year patient survival and graft survival were as follows: NPE 100%, EF 81%, and LF 96% (p < 0.05); and NPE 96%, EF 79%, and LF 96% (p < 0.05). Further investigation into the optimal treatment of biliary atresia should focus on identifying patients at high risk of EF who may benefit from proceeding directly to LTx given the increased risk of post-LTx bacteremia, sepsis, and death after failed HPE.

State-based analysis of necrotizing enterocolitis outcomes.

BACKGROUND: Necrotizing enterocolitis (NEC) is a devastating disease of the newborn. We hypothesized that patient and institution level factors lead to NEC-related outcome disparities. METHODS: We analyzed the California Office of Statewide Health Planning and Development database for the years 1999-2004. We selected NEC-specific ICD-9-CM diagnosis and procedure codes. Mortality rate was the primary outcome measure, and length of stay was used a secondary end-point. We stratified the data by birth weight, gender, race/ethnicity, treatment, median household income, insurance status, admission type (inborn or outborn), and NICU levels. RESULTS: We identified 3328 infants with NEC (incidence of 1 per 1000 live births). Overall mortality within the NEC cohort was 12.5% (13.4 deaths per 100,000 live births). Male or Hispanic neonates were less likely to survive. Socioeconomic factors, including insurance status and parental median household income, were not predictors of mortality. Neonates treated surgically had a greater mortality rate compared with ones treated nonsurgically. PDA was present in 32% of patients with NEC, and these neonates were more likely to undergo gastrointestinal surgery. The odds of NEC-associated mortality in level IIIC units were significantly greater than any other NICU level. Admission type (inborn versus outborn) was not associated with increased mortality. CONCLUSIONS: Disparities in NEC outcomes are multifactorial with patient- and treatment-specific factors contributing significantly to the unfavorable outcomes. These data suggest that advances in prediction modeling, prevention, and treatment algorithms are needed for clinicians and state health planners to positively impact this costly neonatal condition.

Extreme and conventional cardiorespiratory events and epidemiologic risk factors for SIDS.

OBJECTIVE: To test the hypotheses that there is a lack of correlation between extreme events and epidemiologic risk factors for sudden infant death syndrome (SIDS), and if conventional events are normal, their numbers should increase once a circadian decrease in breathing rate is established. In addition, the number of events should decrease with maternal smoking. STUDY DESIGN: Three outcome variables were derived from the Collaborative Home Infant Monitoring Evaluation (CHIME) of 1082 infants: (1) at least 1 extreme event lasting > or = 30 seconds, (2) at least 1 conventional event lasting > or = 20 seconds, and (3) being part of the 50% of infants with the most events. RESULTS: Multivariate logistic regression analyses found that extreme events were not statistically associated with any known SIDS risk factors and occurred less often during the early morning. Healthy term infants had significantly fewer of these events compared with preterm infants, subsequent siblings of infants with SIDS, and infants with an apparent life-threatening event, a finding that was not evident after 43 weeks (3 weeks postterm). Conventional events increased during the night, whereas maternal smoking was associated with a decrease in conventional events. Apneic episodes persisting for > or = 40 seconds occurred in 1.8% of the infants. CONCLUSIONS: Extreme events are associated with immaturity and do not seem to be immediate precursors of or causally related to SIDS.

Relationship of highly sensitive C-reactive protein and lipid levels in adolescents with type 1 diabetes mellitus.

BACKGROUND: Atherosclerosis appears to begin in youth with type 1 diabetes mellitus (T1DM). Highly sensitive C-reactive protein (hsCRP) is an independent marker of cardiovascular disease (CVD) risk in adults, but its relation to dyslipidemia and other CVD risk factors in adolescents with T1DM is unknown. OBJECTIVE: To study the association between lipids and hsCRP in youth with T1DM. DESIGN: Cross-sectional cohort. METHODS: hsCRP and fasting lipids were measured in 74 patients with T1DM, mean age 16.2 +/- 2.62 yr, mean duration of diabetes 7.3 +/- 4.0 yr, and mean hemoglobin A1c (HbA1c) 8.5 +/- 1.3%. According to the American Heart Association/Centers for Disease Control recommendations, hsCRP values were divided into three groups: group 1: <1.0 mg/L, low CVD risk; group 2: 1.0-3.0 mg/L, average CVD risk; and group 3: >3 mg/L, high CVD risk. Univariate linear regression between hsCRP and lipid and clinical parameters was used, with adjustment for age. RESULTS: hsCRP was significantly associated with triglycerides (Tg), apoB, systolic blood pressure (SBP), and diastolic blood pressure (DBP). Subjects in the high CVD risk group had no further worsening of lipids or BP, except for a higher Tg level. ApoB, SBP, and DBP were elevated in females with hsCRP > or =1 compared with the low-risk group, and high-density lipoprotein was decreased. In males, this difference was only significant for SBP. CONCLUSIONS: Elevation of hsCRP to a level > or =1.0 mg/L appears to be associated with elevated lipid levels in adolescents with T1DM, particularly in females. hsCRP is a marker in youth that clusters with dyslipidemia and may indicate an increased CVD risk in youth with T1DM.

Lentiviral vector transduction of a dominant-negative Rev gene into human CD34+ hematopoietic progenitor cells potently inhibits human immunodeficiency virus-1 replication.

Gene therapy for human immunodeficiency virus (HIV)-1 may be performed by introducing into hematopoietic stem cells genes that inhibit replication of HIV-1 using lentiviral vectors. However, production of lentiviral vectors derived from HIV-1 may be inhibited by the gene being carried to inhibit HIV-1 and these vectors could be mobilized by wild-type HIV-1 infecting transduced cells. This study investigates these problems for the delivery of a dominant-negative rev gene humanized revM10 (huM10) by a lentiviral vector. Although most packaging plasmids suffered inhibition of expression of HIV-1 virion proteins by vectors expressing huM10, the packaging plasmids that expressed the highest levels of HIV-1 virion proteins produced vectors at titers that would be sufficient for clinical applications. The vectors carrying huM10 were used to transduce primary human CD34(+) hematopoietic progenitor cells and yielded high-level transduction without toxicity and conferred potent inhibition of HIV-1. The use of lentiviral vectors with deletion of the enhancers and promoter from the LTR (self-inactivating (SIN) vectors) decreased the frequency of vector mobilization by wild-type HIV-1; SIN vectors carrying huM10 were not mobilized detectably. These studies indicate that lentiviral vectors can be made effective for use in gene therapy for HIV-1.

Correlation between high vascular endothelial growth factor-A serum levels and treatment outcome in patients with standard-risk acute lymphoblastic leukemia: a report from Children's Oncology Group Study CCG-1962.

PURPOSE: Many molecular pathways, including cell cycle control, angiogenesis, and drug resistance, mediate tumor growth and survival. Vascular endothelial growth factor-A (VEGF-A) serum levels <40 and >100 pg/mL have been associated with good and poor prognoses, respectively. EXPERIMENTAL DESIGN: The hypothesis was that serum VEGF-A levels in standard-risk acute lymphoblastic leukemia pediatric patients at induction are predictive of event-free survival (EFS). One hundred seventeen patients were entered in CCG-1962 study and randomized into the native and polyethylene glycolated asparaginase arms. VEGF-A levels were quantified by an ELISA assay. RESULTS: All patients had a decrease in VEGF-A levels by day 14 of induction, but they later dichotomized; EFS group levels remained low and event group levels increased. A correlation exists between high VEGF-A levels at entry to induction and time to event. Moreover, 6-year EFS patients have lower end of induction VEGF-A levels (28 +/- 6 pg/mL) than event patients (>100 pg/mL; P < 0.01). Kaplan-Meier curves using various VEGF-A values were produced; with < or =30 at entry into induction (day 0) and < or =60 pg/mL at the end of induction (day 28), patients with low VEGF-A levels had superior EFS (P < 1e-4). Furthermore, patients who had an increase in VEGF-A during induction (DeltaVEGF-positive, days 0-28) were more likely to have an event (P < 1e-4). Bifurcation by asparaginase treatment arm did not alter these results. CONCLUSIONS: These observations strongly support that high VEGF-A levels in induction are an asparaginase treatment-independent predictive marker for EFS. Hence, an anti-VEGF-A therapy should be tested in acute lymphoblastic leukemia.

Preoperative predictors of prolonged postoperative mechanical ventilation in children following scoliosis repair.

Scoliosis is associated with progressive restrictive lung disease and an increased risk of pulmonary complications following surgical correction. Identification of higher risks for prolonged postoperative mechanical ventilation (MV) improves postoperative care. Our objective was to determine if preoperative pulmonary function tests (PFT) predict prolonged postoperative MV (defined as MV >or=3 days). We correlated preoperative PFT (forced expired volume in 1 sec, FEV1; vital capacity, VC; inspiratory capacity, IC; maximal inspiratory pressure, MIP; total lung capacity, TLC; and residual volume, RV) and postoperative MV days in 125 patients who had scoliosis surgery (aged 13.7 +/- 3.0 (SD) years) from January 1990-July 2001. We had 71 male and 54 female patients. Scoliosis types were 13 congenital, 27 idiopathic, 57 neuromuscular, 23 syndrome/tumor, and 5 kyphoscoliosis. Forty patients (32%) had postoperative MV >or=3 days. Independent factors likely requiring postoperative MV >or=3 days were neuromuscular scoliosis (P < 0.001) and FEV1 <40% predicted. Independent factors most likely were: neuromuscular scoliosis with preoperative FEV1 <40% predicted (P < 0.01). Independent factors most unlikely were: idiopathic scoliosis (P < 0.002). VC <60% predicted, IC <30 ml/kg, TLC <60% predicted, and MIP <60 cm H2O correlated with postoperative MV >or=3 days (P < 0.05). We found no association between RV and postoperative MV. FEV1 <40% predicted, VC <60% predicted, IC <30 ml/kg, TLC <60% predicted, MIP <60 cm H2O, and neuromuscular disease each correlated with prolonged postoperative MV. Neuromuscular disease or a preoperative FEV(1) <40% predicted were more likely, and older children with neuromuscular disease and FEV1 <40% predicted were most likely to require prolonged postoperative MV (P < 0.01). Clearly FEV1, and possibly VC, IC, TLC, and MIP, may increase accuracy in predicting the need for prolonged postoperative MV.

Multiparametric magnetic resonance imaging for prostate cancer improves Gleason score assessment in favorable risk prostate cancer.

PURPOSE: Magnetic resonance imaging (MRI) guidance may improve the accuracy of Gleason score (GS) determination by directing the biopsy to regions of interest (ROI) that are likely to harbor high-grade prostate cancer (CaP). The aim of this study was to determine the frequency and predictors of GS upgrading when a subsequent MRI-guided biopsy is performed on patients with a diagnosis of GS 6 disease on the basis of conventional, transrectal ultrasound-guided biopsy. METHODS AND MATERIALS: A consecutive series of 245 men with a diagnosis of low-risk CaP (ie, cT1c, GS 6, prostate-specific antigen <10) based on transrectal ultrasound-guided biopsy was enrolled in an active surveillance protocol that used subsequent MRI-guided biopsy for confirmation of GS. ROIs were categorized on a scale of 1 to 5. The Artemis ultrasound-MRI fusion device was used to perform targeted biopsies of ROIs as well as systematic biopsies from a software-based 12-point map. Predictors of GS upgrading were analyzed using univariate and multivariate analyses. RESULTS: Fusion biopsy resulted in 26% of patients having GS upgrading (GS 3+4 in 18%, 4+3 in 5%, and 8-9 in 3%). Of the 72% of patients with ROIs appropriate for targeting, targeted cores upgraded the GS in 18%, whereas systematic cores upgraded the GS in 24%. In patients without targeted biopsy, GS upgrading was seen in 14%. On multivariate analysis, a category 5 ROI was the most significant predictor of GS upgrading with an odds ratio of 10.56 (P < .01). CONCLUSIONS: Nearly 25% of men with GS 6 CaP diagnosed by standard transrectal ultrasound biopsy may experience GS upgrading when a subsequent MRI-ultrasound fusion biopsy is performed. The most important single predictor of upgrading is a category 5 ROI on multiparametric MRI. GS upgrading may influence treatment decisions. Therefore, MRI-guided biopsy should be considered prior to formulating a management strategy in patients whose conventional biopsy reveals low-risk CaP.

Inverse association between brown adipose tissue activation and white adipose tissue accumulation in successfully treated pediatric malignancy.

BACKGROUND: Although the accumulation of white adipose tissue (WAT) is a risk factor for disease, brown adipose tissue (BAT) has been suggested to have a protective role against obesity. OBJECTIVE: We studied whether changes in BAT were related to changes in the amounts of subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) in children treated for malignancy. DESIGN: We examined the effect of BAT activity on weight, SAT, and VAT in 32 pediatric patients with cancer whose positron emission tomography-computed tomography (PET-CT) scans at diagnosis showed no BAT activity. Changes in weight, SAT, and VAT from diagnosis to remission for children with metabolically active BAT at disease-free follow-up (BAT+) were compared with those in children without visualized BAT when free of disease (BAT-). RESULTS: Follow-up PET-CT studies (4.7 ± 2.4 mo later) after successful treatment of the cancer showed BAT+ in 19 patients but no active BAT (BAT-) in 13 patients. BAT+ patients, in comparison with BAT- patients, gained significantly less weight (3.3 ± 6.6% compared with 11.0 ± 11.6%; P = 0.02) and had significantly less SAT (18.2 ± 26.5% compared with 67.4 ± 71.7%; P = 0.01) and VAT (22.6 ± 33.5% compared with 131.6 ± 171.8%; P = 0.01) during treatment. Multiple regression analysis indicated that the inverse relations between BAT activation and measures of weight, SAT, and VAT persisted even after age, glucocorticoid treatment, and the season when the PET-CT scans were obtained were accounted for. CONCLUSION: The activation of BAT in pediatric patients undergoing treatment of malignancy is associated with significantly less adipose accumulation. This trial was registered at clinicaltrials.gov as NCT01517581.

Willingness to respond in a disaster: a pediatric nurse practitioner national survey.

OBJECTIVE: The objective of this study was to examine factors associated with pediatric nurse practitioners (PNPs) reporting to work in the event of a disaster. METHODS: An anonymous national survey of PNPs was conducted. Several domains were explored, including demographics, personal preparedness plans, disaster training, prior disaster experience, and likelihood of responding in the event of a disaster. A logistic regression analysis was conducted to determine which factors were associated with the respondent's likelihood of responding in the event of a disaster. RESULTS: Factors associated with increased likelihood of responding included gender (being a male PNP), military experience, and disaster training. The most significant factor associated with an increased likelihood of responding to work during a disaster was having a specified role in the workplace disaster plan. PNPs with a specified role were three times more likely to respond than were those without a specified role. CONCLUSIONS: PNPs are health care workers with advanced skill sets. This untapped resource is available to provide care for a vulnerable population: our children. Disaster planners should explore the possibility of utilizing these highly skilled health care workers in their disaster plans.

Differential branch pulmonary artery growth after the Norwood procedure with right ventricle-pulmonary artery conduit versus modified Blalock-Taussig shunt in hypoplastic left heart syndrome.

OBJECTIVES: The Norwood procedure with right ventricle-pulmonary artery conduit is thought to improve postoperative hemodynamics in hypoplastic left heart syndrome, but its effects on pulmonary artery growth are unknown. This study evaluated pulmonary artery growth after the Norwood procedure in patients with a right ventricle-pulmonary artery conduit as compared with patients with a modified Blalock-Taussig shunt. METHODS: A total of 159 patients at our institution underwent the Norwood procedure between January 2000 and September 2005. Patients were divided into group A or B if they had a modified Blalock-Taussig shunt (n = 103) or a right ventricle-pulmonary artery conduit (n = 56). Angiograms from the pre-Glenn catheterizations were used to measure pulmonary artery size and assess shunt stenosis (n = 64). RESULTS: Fifty-five (53.4%) patients in group A versus 40 (71.4%) in group B underwent Glenn surgery. Group B patients often required an additional shunt (modified Blalock-Taussig) before the Glenn procedure because of hypoxemia (8/40 vs 1/55; P = .004). Branch pulmonary artery growth was better in group B patients who did not require an additional shunt (Nakata index 212 vs 169 mm(2)/m(2); P = .004) and more balanced than in group A (right pulmonary artery/left pulmonary artery ratio = 1.02 vs 1.39; P = .001) as a result of greater left pulmonary artery size (29 vs 19 mm(2); P = .001). However, group B experienced more shunt stenosis (8/32 vs 2/32; P = .001), underwent the Glenn operation earlier (192 vs 246 days; P = .03), and had central pulmonary artery hypoplasia develop more often than group A patients (25/32 vs 14/32; P = .01). CONCLUSION: The Norwood procedure with a right ventricle-pulmonary artery conduit promotes better distal left pulmonary artery growth resulting in more balanced branch pulmonary artery size, but central pulmonary artery hypoplasia occurs more often. Early right ventricle-pulmonary artery conduit stenosis also increases the need for additional shunting or early Glenn surgery.

A survey of academic surgeons: work, stress, and research.

BACKGROUND: An academic surgeon's workweek is divided among patient care, administrative duties, education, and research. The time available for research activities may change as a surgeon's career evolves. We sought to determine involvement of academic surgeons in research and to assess how this research endeavor was affected by demographic and workplace characteristics. METHODS: We constructed a survey to explore the following 4 domains: demographics, time allotment, research activities, and effects of stressors. We distributed the survey to members of the Society of University Surgeons. In addition to performing descriptive statistics, we defined an active researcher as someone with a funding source who devoted 15% or more work hours to research. Using this definition, we performed statistical analyses to assess the significance of independent variables on research. Stress factors were evaluated on a Likert scale with responses ranging from 1 (not at all) to 5 (extremely). RESULTS: We received 314 completed surveys (response rate 23%). Of the respondents, 274 (87%) stated that they were involved in some kind of research activity; however, only 143 (46%) were active researchers. Using univariate logistic regression analysis, younger respondents and surgeons who practiced for more than 10 years were more likely to be active researchers (odds ratio [OR]: 1.93, confidence interval [CI]: 1.51-2.46 and OR: 2.06, CI: 1.64-2.59, respectively). Males were less likely than females to be active researchers (OR: 0.32, CI: 016-0.67); however, by multivariate analysis, we found that the "years in practice" of an active researcher was the most significant predictor of research activity, whereas age and sex were not. In regard to stress, most respondents reported scores of 1-3 for all 7 stressors, which is consistent with minimal to moderate stress. CONCLUSION: Academic surgeons are involved actively in research; however, this involvement decreases as other professional responsibilities increase. To optimize the surgical research environment, departments should invest time and resources in young investigators to prevent them from decreasing their research activities.

Outcome analysis of neonates with congenital diaphragmatic hernia treated with venovenous vs venoarterial extracorporeal membrane oxygenation.

PURPOSE: Venoarterial extracorporeal membrane oxygenation (ECMO) (VA) is used more commonly in neonates with congenital diaphragmatic hernia (CDH) than venovenous ECMO (VV). We hypothesized that VV may result in comparable outcomes in infants with CDH requiring ECMO. METHODS: We retrospectively analyzed the Extracorporeal Life Support Organization (ELSO) database (1991-2006). Multivariate logistic regression analyses were used to compare VV- and VA-associated mortality. RESULTS: Four thousand one hundred fifteen neonates required ECMO, with an overall mortality rate of 49.6%. Venoarterial ECMO was used in 82% and VV in 18% of neonates. Pre-ECMO inotrope use and complications were equivalent between VA and VV. The mortality rate for VA and VV was 50% and 46%, respectively. After adjusting for birth weight, gestational age, prenatal diagnosis, ethnicity, Apgar scores, pH less than 7.20, Paco(2) greater than 50, requiring high-frequency ventilation, and year of ECMO, there was no difference in mortality between VV vs VA. Renal complications and on-ECMO inotrope use were more common with VV, whereas neurologic complications were more common with VA. The conversion rate from VV to VA was 18%; conversion was associated with a 56% mortality rate. CONCLUSION: The short-term outcomes of VV and VA are comparable. Patients with CDH who fail VV may be predisposed to a worse outcome. Nevertheless, VV offers equal benefit to patients with CDH requiring ECMO while preserving the native carotid.

Training medical staff for pediatric disaster victims: a comparison of different teaching methods.

OBJECTIVE: The goal of this study was to assess the effectiveness of the different types of healthcare worker training in pediatric disaster medicine knowledge over time and to analyze the effects of training type on healthcare workers' attitude toward pediatric disaster medicine. DESIGN: Prospective randomized controlled longitudinal study. SETTING: Large, urban, tertiary academic children's hospital. SUBJECTS: Physicians and nurses employed at Children's Hospital Los Angeles randomly selected from a global hospital e-mail server over a 3-week time frame were invited to participate and receive an incentive on completion. Forty-three controls and 42 intervention subjects (22 lecture + tabletop exercise, 20 lecture only) completed the study. Subjects with disaster training in the prior 6 months were excluded. INTERVENTIONS: Subjects underwent a didactic lecture or a combination of didactic lecture and tabletop exercise. Preintervention and postintervention testing took place using a 37-question multiple-choice test on pediatric disaster medical topics. Posttesting took place immediately after intervention and then 1, 3, and 6 months after the intervention. Subjects also were surveyed before and after intervention regarding their attitudes toward pediatric disaster medicine. MAIN OUTCOME MEASURES: (1) Scores on a 37-question knowledge test and (2) Likert scores on self-perceptions of knowledge, comfort, and interest in pediatric disaster medicine. RESULTS: Regardless of intervention type, participant scores on a postintervention pediatric disaster medicine tests over a 6-month period increased and remained well above pretest means for intervention and control pretest scores. There were no differences in scores comparing type of intervention. However, subjects who underwent the tabletop simulation had a better sense of knowledge and comfort with the topics compared with those who only underwent a didactic lecture. CONCLUSIONS: Didactic lecture and tabletop exercises both increase healthcare worker's knowledge of pediatric disaster medical topics. This knowledge seems to be retained for at least 6 months postintervention. The addition of the tabletop exercise to a standard didactic lecture may increase a learner's sense of knowledge and comfort with disaster topics, which may in turn lead to increased staff participation in the event of an actual disaster.

Disaster management among pediatric surgeons: preparedness, training and involvement.

INTRODUCTION: Contemporary events in the United States (eg, September 2001, school shootings), Europe (eg, Madrid train bombings), and the Middle East have raised awareness of mass casualty events and the need for a capable disaster response. Recent natural disasters have highlighted the poor preparation and infrastructure in place to respond to mass casualty events. In response, public health policy makers and emergency planners developed plans and prepared emergency response systems. Emergency response providers include first responders, a subset of emergency professionals, including firemen, law enforcement, paramedics, who respond to the incident scene and first receivers, a set of healthcare workers who receive the disaster victims at hospital facilities. The role of pediatric surgeons in mass casualty emergency response plans remains undefined. The authors hypothesize that pediatric surgeons' training and experience will predict their willingness and ability to be activated first receivers. The objective of our study was to determine the baseline experience, preparedness, willingness, and availability of pediatric surgeons to participate as activated first receivers. METHODS: After institutional review board approval, the authors conducted an anonymous online survey of members of the American Pediatric Surgical Association in 2007. The authors explored four domains in this survey: (1) demographics, (2) disaster experience and perceived preparedness, (3) attitudes regarding responsibility and willingness to participate in a disaster response, and (4) availability to participate in a disaster response. The authors performed univariate and bivariate analyses to determine significance. Finally, the authors conducted a logistic regression to determine whether experience or preparedness factors affected the respondent's availability or willingness to respond to a disaster as a first receiver RESULTS: The authors sent 725 invitations and received 265 (36.6 percent) completed surveys. Overall, the authors found that 77 percent of the respondents felt "definitely" responsible for helping out during a disaster but only 24 percent of respondents felt "definitely"prepared to respond to a disaster. Most felt they needed additional training, with 74 percent stating that they definitely or probably needed to do more training. Among experiential factors, the authors found that attendance at a national conference was associated with the highest sense of preparedness. The authors determined that subjects with actual disaster experience were about four times more likely to feel prepared than those with no disaster experience (p < 0.001). The authors also demonstrated that individuals with a defined leadership position in a disaster response plan are twice as likely to feel prepared (p = 0.002) and nearly five times more willing to respond to a disaster than those without a leadership role. The authors found other factors that predicted willingness including the following: a contractual agreement to respond (OR 2.3); combat experience (OR 2.1); and prior disaster experience (OR 2.0). Finally, the authors found that no experiential variables or training types were associated with an increased availability to respond to a disaster. CONCLUSIONS: A minority of pediatric surgeons feel prepared, and most feel they require more training. Current training methods may be ineffectual in building a prepared and willing pool of first receivers. Disaster planners must plan for healthcare worker related issues, such as transportation and communication. Further work and emphasis is needed to bolster participation in disaster preparedness training.

Club drug use in los angeles among young men who have sex with men.

Little is known about young men who have sex with men's use of club drugs and the risk factors associated with such use. A structured survey was administered in 2005 to 496 young men who were 18-22 years old (40% were 18-19 years old); self-identified as with a same-sex sexuality (83%), bisexual (16%), and/or had had sex with a man (97%); Caucasian (35%), African American (24%), and Latino of Mexican descent (40%). Subjects were recruited from gay-identified venues in Los Angeles, California, using a venue-based probability sampling design. Descriptive statistics revealed a high prevalence of drug and club drug use. Regression analyses revealed risk factors associated with recent club drug use, including place of residence, religiosity, disclosure of sexuality to family, frequency of attendance at bars/clubs, and involvement in sexual exchange and street economy. Limitations and implications of this research are discussed.

In vivo transduction by intravenous injection of a lentiviral vector expressing human ADA into neonatal ADA gene knockout mice: a novel form of enzyme replacement therapy for ADA deficiency.

Using a mouse model of adenosine deaminase-deficient severe combined immune deficiency syndrome (ADA-deficient SCID), we have developed a noninvasive method of gene transfer for the sustained systemic expression of human ADA as enzyme replacement therapy. The method of delivery is a human immunodeficiency virus 1-based lentiviral vector given systemically by intravenous injection on day 1 to 2 of life. In this article we characterize the biodistribution of the integrated vector, the expression levels of ADA enzyme activity in various tissues, as well as the efficacy of systemic ADA expression to correct the ADA-deficient phenotype in this mouse model. The long-term expression of enzymatically active ADA achieved by this method, primarily from transduction of liver and lung, restored immunologic function and significantly extended survival. These studies illustrate the potential for sustained in vivo production of enzymatically active ADA, as an alternative to therapy by frequent injection of exogenous ADA protein.