Search

436 Background: Neoadjuvant chemotherapy (NA CT) may improve surgical selection for resectable (R) PDAC, and margin negative resection in borderline resectable (BR) PDAC. Optimal duration of NA CT is unknown, as is the role of XRT with modern chemotherapy. We compared survival outcomes by duration of NA CT and NA CT + XRT. Methods: Patients with R or BR PDAC who underwent NA CT with or without XRT and followed by curative resection were included in this analysis. Data was extracted from an IRB approved pancreatic cancer database at Indiana University. Disease Free (DFS) and Overall (OS) survival were calculated from the surgery date and compared between: 1) < 3 v ≥ 3 months NA CT and 2) NA CT with/without XRT. Results: Between Summer 2008 and Summer 2018, 116 patients received NA CT with or without XRT and completed surgical resection. Median (range) age was 63 years (36, 84), stages were R=47%, BR=53%. Most patients received modified FOLFIRINOX or FOLFIRINOX (59 %), or gemcitabine/nab-paclitaxel (13%) and 24% received XRT. There were four (3 %) pathologic complete responders, all in the ≥ 3 mo NA CT + XRT group. Percent node positive was lower in NA CT + XRT versus NA CT only (median 0% vs 7.4%, p < 001), but did not differ by duration of NA CT. With a median (range) follow-up time of 13.7 mo (0.7, 83.0), median OS was 22.5 mo (19.5, 29.8) with < 3 mo NA CT versus 16.3 (12.2, 18.9) with ≥ 3 mo NA CT (p = 0.02) and was 22.6 mo (17.0, 82.9) with NA CT + XRT versus 19.5 (13.1, 22.5) in NA CT only (p = 0.03). There was no difference in DFS by duration of NA CT or XRT. Conclusions: In this study, patients who received a shorter course of chemotherapy and radiation had improved mOS when calculated from the surgery date. While this unexpected results could reflect selection bias of therapy, further analysis will account for tumor stage at diagnosis, perioperative complications and use propensity score adjustment to examine/adjust for possible treatment selection bias.

We compared survival outcomes following myeloablative allotransplant (MAT) or cyclophosphamide/fludarabine (Cy/Flu) nonmyeloablative allotransplant (NMAT) for 165 patients with acute myelogenous leukemia (AML) in remission or without frank relapse. Patients who received NMAT were more likely to be older and have secondary AML and lower performance status. At a median follow-up of 61 months, median event-free survival and overall survival survival were not different between NMAT and MAT in univariate as well as multivariate analyses. Cy/Flu NMAT may provide similar disease control and survival when compared with MAT in patients with AML in remission or without frank relapse.

Insertion of a gastric tube (nasogastric [NG] or orogastric [OG]) is a common medical intervention in children for a wide range of clinical indications, including delivery of enteral nutrition, administration of medications, decompression of the stomach following intestinal obstruction or surgery, irrigation of the stomach, and performance of diagnostic procedures (Phillips, 2006). When the gastrointestinal (GI) tract is intact and the need for assisted feeding is expected to be short-term, feeding by an NG/OG tube is preferred over feeding through a gastrostomy tube (Kirby, Delegge, & Fleming, 1995). Small-bore NG/OG tubes are usually used for enteral nutrition because they are made of soft polyurethane that remain flexible when exposed to gastric acid; thus, patient discomfort is reduced (Sriram, Jayanthi, Lakshmi, & George, 1997). Small-bore NG/OG tubes also reduce the risk of aspiration because the smaller diameter does not affect the competency of the lower esophageal sphincter as much as large-bore tubes (Phillips, 2006; Sriram et al., 1997); however, small-bore tubes are known to be misplaced on insertion and to displace during use (Ellett & Beckstrand, 1999; Ellett, Maahs, & Forsee, 1998; Metheny, 1988; Williams & Leslie, 2004).

BACKGROUND: “Systems of care” are strengths-based approaches to treating adolescents and others with disruptive disorders. However, little is known about why some adolescents improve and others do not. OBJECTIVE: To examine changes in personal strengths and family functioning as predictors of behavioral and social functioning among adolescents with disruptive disorders who participated in a system of care program. DESIGN: Secondary analyses of data from 114 adolescents (12-17 years of age) with disruptive disorders and their caregivers who participated in the Dawn Project Evaluation Study. Caregivers completed in-depth interviews conducted by trained data collectors using standardized questionnaires. Baseline and 12- month data are reported here. RESULTS: Improvement in personal strengths was a significant predictor of improvement in adolescent behavioral and social functioning, controlling for demographics ( p < .001). CONCLUSION: In adolescents with disruptive disorders, psychiatric nurses should focus on enhancing adolescents’ personal strengths to improve behavioral and social functioning.

Building Our Solutions and Connections (BOSC) focused on enhancing problem-solving skills (PSS) of primary caregivers of children with mental health problems. Aims were determining feasibility, acceptability, and effect size ( ES ) estimates for depression, burden, personal control, and PSS. Methods: Caregivers were randomized to BOSC ( n = 30) or wait-list control (WLC) groups ( n = 31). Data were collected at baseline, post-intervention, and 3 and 6 months post-intervention. Results: Three-months post-intervention, ES for burden and personal control were .07 and .08, respectively. ES for depressed caregivers for burden and personal control were 0.14 and 0.19, respectively. Conclusions: Evidence indicates that the intervention had desired effects.

Background Provider recommendation is a predictor of colorectal cancer (CRC) screening. Purpose To compare the effects of two clinic-based interventions on patient–provider discussions about CRC screening. Design Two-group RCT with data collected at baseline and 1 week post-intervention. Setting/participants African-American patients that were non-adherent to CRC screening recommendations ( n =693) with a primary care visit between 2008 and 2010 in one of 11 urban primary care clinics. Intervention Participants received either a computer-delivered tailored CRC screening intervention or a nontailored informational brochure about CRC screening immediately prior to their primary care visit. Main outcome measures Between-group differences in odds of having had a CRC screening discussion about a colon test, with and without adjusting for demographic, clinic, health literacy, health belief, and social support variables, were examined as predictors of a CRC screening discussion using logistic regression. Intervention effects on CRC screening test order by PCPs were examined using logistic regression. Analyses were conducted in 2011 and 2012. Results Compared to the brochure group, greater proportions of those in the computer-delivered tailored intervention group reported having had a discussion with their provider about CRC screening (63% vs 48%, OR=1.81, p p -values Conclusions The computer-delivered tailored intervention was more effective than a nontailored brochure at stimulating patient–provider discussions about CRC screening. Those who received the computer-delivered intervention also were more likely to have a CRC screening test (fecal occult blood test or colonoscopy) ordered by their PCP. Trial registration This study is registered at www.clinicaltrials.gov NCT00672828.

Background Communication problems between family surrogates and intensive care unit (ICU) clinicians have been documented, but few interventions are effective. Nurses have the potential to play an expanded role in ICU communication and decision making. Objectives To conduct a pilot randomized controlled trial of the family navigator (FN), a distinct nursing role to address family members' unmet communication needs early in an ICU stay. Methods An interprofessional team developed the FN protocol. A randomized controlled pilot intervention trial of the FN was performed in a tertiary referral hospital's ICU to test the feasibility and acceptability of the intervention. The intervention addressed informational and emotional communication needs through daily contact by using structured clinical updates, emotional and informational support modules, family meeting support, and follow-up phone calls. Results Twenty-six surrogate/patient pairs (13 per study arm) were enrolled. Surrogates randomized to the intervention had contact with the FN on 90% or more of eligible patient days. All surrogates agreed that they would recom mend the FN to other families. Open-ended comments from both surrogates and clinicians were uniformly positive. Conclusions Having a fully integrated nurse empowered to facilitate decision making is a feasible intervention in an ICU and is well-received by ICU families and staff. A larger randomized controlled trial is needed to demonstrate impact on important outcomes, such as surrogates' well-being and decision quality.

IntroductionIt is increasingly essential for medical researchers to be literate in statistics, but the requisite degree of literacy is not the same for every statistical competency in translational research. Statistical competency can range from ‘fundamental’ (necessary for all) to ‘specialized’ (necessary for only some). In this study, we determine the degree to which each competency is fundamental or specialized.MethodsWe surveyed members of 4 professional organizations, targeting doctorally trained biostatisticians and epidemiologists who taught statistics to medical research learners in the past 5 years. Respondents rated 24 educational competencies on a 5-point Likert scale anchored by ‘fundamental’ and ‘specialized.’ResultsThere were 112 responses. Nineteen of 24 competencies were fundamental. The competencies considered most fundamental were assessing sources of bias and variation (95%), recognizing one’s own limits with regard to statistics (93%), identifying the strengths, and limitations of study designs (93%). The least endorsed items were meta-analysis (34%) and stopping rules (18%).ConclusionWe have identified the statistical competencies needed by all medical researchers. These competencies should be considered when designing statistical curricula for medical researchers and should inform which topics are taught in graduate programs and evidence-based medicine courses where learners need to read and understand the medical research literature.

Recent studies have suggested that plasma-derived proteins may be potential biomarkers relevant for graft-versus-host disease and/or non-relapse mortality occurring after allogeneic blood or marrow transplantation. However, none of these putative biomarkers have been assessed in patients treated either with human leukocyte antigen-haploidentical blood or marrow transplantation or with post-transplantation cyclophosphamide, which has been repeatedly associated with low rates of severe acute graft-versus-host disease, chronic graft-versus-host disease, and non-relapse mortality. We explored whether seven of these plasma-derived proteins, as measured by enzyme-linked immunosorbent assays, were predictive of clinical outcomes in post-transplantation cyclophosphamide-treated patients using plasma samples collected at serial predetermined timepoints from patients treated on prospective clinical studies of human leukocyte antigen-haploidentical (n=58; clinicaltrials.gov Identifier: 00796562) or human leukocyte antigen-matched-related or -unrelated (n=100; clinicaltrials.gov Identifiers: 00134017 and 00809276) T-cell-replete bone marrow transplantation. Day 30 levels of interleukin-2 receptor α, tumor necrosis factor receptor 1, serum STimulation-2 (IL1RL1 gene product), and regenerating islet-derived 3-α all had high areas under the curve of 0.74-0.97 for predicting non-relapse mortality occurrence by 3 months post-transplant in both the human leukocyte antigen-matched and human leukocyte antigen-haploidentical cohorts. In both cohorts, all four of these proteins were also predictive of subsequent non-relapse mortality occurring by 6, 9, or 12 months post-transplant and were significantly associated with non-relapse mortality in univariable analyses. Furthermore, day 30 elevations of interleukin-2 receptor α were associated with grade II-IV and III-IV acute graft-versus-host disease occurring after day 30 in both cohorts. These data confirm that plasma-derived proteins previously assessed in other transplantation platforms appear to retain prognostic and predictive utility in patients treated with post-transplantation cyclophosphamide.

Objective: To characterize patients who voluntarily enrolled in an electronic health information exchange (HIE) program designed to share data between Veterans Health Administration (VHA) and non-VHA institutions.Materials and Methods: Patients who agreed to participate in the HIE program were compared to those who did not. Patient characteristics associated with HIE enrollment were examined using a multivariable logistic regression model. Variables selected for inclusion were guided by a health care utilization model adapted to explain HIE enrollment. Data about patients’ sociodemographics (age, gender), comorbidity (Charlson index score), utilization (primary and specialty care visits), and access (distance to VHA medical center, insurance, VHA benefits) were obtained from VHA and HIE electronic health records.Results: Among 57 072 patients, 6627 (12%) enrolled in the HIE program during its first year. The likelihood of HIE enrollment increased among patients ages 50–64, of female gender, with higher comorbidity, and with increasing utilization. Living in a rural area and being unmarried were associated with decreased likelihood of enrollment.Discussion and Conclusion: Enrollment in HIE is complex, with several factors involved in a patient’s decision to enroll. To broaden HIE participation, populations less likely to enroll should be targeted with tailored recruitment and educational strategies. Moreover, inclusion of special populations, such as patients with higher comorbidity or high utilizers, may help refine the definition of success with respect to HIE implementation.

The study objective was to examine factors that influence African American (AA) family members' end-of-life care decision outcomes for a relative who recently died from serious illness.A cross-sectional descriptive study design was used. Binary logistic and linear regressions were used to identify factors associated with decision regret and decisional conflict. Forty-nine bereaved AA family members of AA decedents with serious illness who died two to six months prior to enrollment were recruited from the palliative care program in a safety net hospital and a metropolitan church in the Midwest. Measurements used were the Decisional Conflict, Decision Regret, Beliefs and Values, and Quality of Communication scales.Family members who reported higher quality of communication with health care providers had lower decisional conflict. Family members of decedents who received comfort-focused care (CFC) had significantly less decision regret than family members of those who received life-prolonging treatment (LPT). Family members who reported stronger beliefs and values had higher quality of communication with providers and lower decisional conflict.This research adds to a small body of literature on correlates of end-of-life decision outcomes among AAs. Although AAs' preference for aggressive end-of-life care is well-documented, we found that receipt of CFC was associated with less decision regret. To reduce decisional conflict and decision regret at the end of life, future studies should identify strategies to improve family member-provider communication, while considering relevant family member and decedent characteristics.

// James Haley 1 , Sunil Tomar 1 , Nicholas Pulliam 1 , Sen Xiong 1 , Susan M. Perkins 2 , Adam R. Karpf 3 , Sumegha Mitra 1, 4 , Kenneth P. Nephew 1, 5, 6 , Anirban K. Mitra 1, 5, 7 1 Medical Sciences Program, Indiana University School of Medicine, Bloomington, IN 47405, USA 2 Department of Biostatistics, Indiana University, Indianapolis, IN 46202, USA 3 Eppley Institute and Fred and Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE 68198, USA 4 Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN 46202, USA 5 Indiana University Melvin and Bren Simon Cancer Center, Indianapolis, IN 46202, USA 6 Department of Cellular and Integrative Physiology, Indiana University School of Medicine, Indianapolis, IN 46202, USA 7 Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN 46202, USA Correspondence to: Anirban K. Mitra, email: anmitra@indiana.edu Keywords: ovarian cancer, migration, invasion, proliferation, clonogenicity Received: January 27, 2016 Accepted: April 10, 2016 Published: April 27, 2016 ABSTRACT Genomic analysis of ovarian cancer cell lines has revealed a panel that best represents the most common ovarian cancer subtype, high-grade serous ovarian cancer (HGSOC). However, these HGSOC-like cell lines have not been extensively applied by ovarian cancer researchers to date, and the most commonly used cell lines in the ovarian cancer field do not genetically resemble the major clinical type of the disease. For the HGSOC-like lines to serve as suitable models, they need to be characterized for common functional assays. To achieve that objective, we systematically studied a panel of HGSOC cells CAOV3, COV362, Kuramochi, OVCAR4, OVCAR5, OVCAR8, OVSAHO and SNU119 for migration, invasion, proliferation, clonogenicity, EMT phenotype and cisplatin resistance. They exhibited a range of efficacies and OVCAR5, OVCAR8 and Kuramochi were the most aggressive. SNU119 and OVSAHO cells demonstrated the lowest functional activities. Wide differences in expression of EMT markers were observed between cell lines. SNU119 were the most epithelial and OVCAR8 had the most mesenchymal phenotype. COV362 was the most resistant to cisplatin while CAOV3 was the most sensitive. Taken together, our systematic characterization represents a valuable resource to help guide the application of HGSOC cells by the cancer research community.

The Virtual Lifetime Electronic Record (VLER) Health program provides the Veterans Health Administration (VHA) a framework whereby VHA providers can access the veterans’ electronic health record information to coordinate healthcare across multiple sites of care. As an early adopter of VLER, the Indianapolis VHA and Regenstrief Institute implemented a regional demonstration program involving bi-directional health information exchange (HIE) between VHA and non-VHA providers. The aim of the study is to determine whether implementation of VLER HIE reduces 1 year VHA medical costs. A cohort evaluation with a concurrent control group compared VHA healthcare costs using propensity score adjustment. A CHEERs compliant checklist was used to conduct the cost evaluation. Patients were enrolled in the VLER program onsite at the Indianapolis VHA in outpatient clinics or through the release-of-information office. VHA cost data (in 2014 dollars) were obtained for both enrolled and nonenrolled (control) patients for 1 year prior to, and 1 year after, the index date of patient enrollment. There were 6104 patients enrolled in VLER and 45,700 patients in the control group. The annual adjusted total cost difference per patient was associated with a higher cost for VLER enrollees $1152 (95% CI: $807–1433) (P

In the study we describe adaptive functioning in children with epilepsy whose primary caregivers identified them as having learning problems. This was a cross-sectional study of 50 children with epilepsy and learning problems. Caregivers supplied information regarding the child’s adaptive functioning and behavior problems. Children rated their self-concept and completed a battery of neuropsychological tests. Mean estimated IQ (PPVT-III) in the participant children was 72.8 (SD = 18.3). On average, children scored 2 standard deviations below the norm on the Vineland Adaptive Behavior Scale–II and this was true even for children with epilepsy who had estimated IQ in the normal range. In conclusion, children with epilepsy and learning problems had relatively low adaptive functioning scores and substantial neuropsychological and mental health problems. In epilepsy, adaptive behavior screening can be very informative and guide further evaluation and intervention, even in those children whose IQ is in the normal range.

PURPOSE The aim of this study was to describe strategies for recruiting participants into an intervention study that focused on improving problem-solving skills in caregivers of children with mental health problems. BACKGROUND Caregivers of children with mental health problems report feeling physically and psychologically overwhelmed and have high rates of depression because of the demands of caregiving. Research on the needs of these caregivers and interventions to ameliorate their stress is needed. However, recruiting this population can be particularly difficult because of the stigma of mental illness. Available literature on recruitment of caregivers of persons with physical illness cannot be transferred to caregivers of children with mental health problems because of the different caregiving situations. There is a need to identify effective recruitment strategies to reduce cost and answer research questions. Clinical nurse specialists have the skills to facilitate the recruitment of research participants. We revised and expanded health system referrals, community outreach, and recruiting advertisement (ads). When these strategies did not increase recruitment, radio ads were used. The Andersen's Behavioral Model of Health Services Utilization was selected as a guiding framework. OUTCOME Radio ads were the most effective strategy for recruiting caregivers of children with mental health problems for this study. CONCLUSION Recruitment was ultimately successful because we were flexible and made decisions consistent with the Andersen's Behavioral Model of Health Services Utilization. IMPLICATIONS Clinical nurse specialists who study this population of caregivers should really consider the use of radio ads and systematically track which recruitment strategies lead to the greatest number of participants screened, eligible, and enrolled into studies.

The mortality in the ICU for pediatric HSCT recipients remains high. Early pulmonary complications continue to be an obstacle to the survival. We hypothesize OI is a predictor for mortality in critically ill pediatric HSCT recipients. Retrospective review of pediatric HSCT recipients between 2002 and 2010 who required intensive care during the same hospital admission as their transplant. Twenty-eight patients accounted for 31 ICU admissions. Twenty-six (84%) admissions required mechanical ventilation. Ten (38%) mechanically ventilated admissions were placed on HFOV. Mortality of those mechanically ventilated was 70%. An OI ≥ 20 at any point during ventilation was associated with 94% mortality, while an OI ≥ 25 had 100% mortality. There was a significant association between maximum OI at any point during mechanical ventilation and ICU mortality, with the odds of dying increasing by 13% for each unit increase of max OI (OR = 1.13, 95% CI = 1.01-1.26, p = 0.03). An OI of 20 had a sensitivity of 0.89 and specificity of 0.83 for predicting mortality. OI has a strong association with ICU mortality among pediatric stem cell recipients.

Ubiquitous pro-oxidative stressor ultraviolet B radiation (UVB) to human or mouse skin generates platelet-activating factor (PAF) and novel oxidatively modified glycerophosphocholines (Ox-GPCs) with PAF-receptor (PAF-R) agonistic activity. These lipids mediate systemic immunosuppression in a process involving IL-10. The current studies sought to determine the functional significance of UVB-mediated systemic immunosuppression in an established model of murine melanoma. We show that UVB irradiation augments B16F10 tumor growth and is dependent on host, but not melanoma cell; PAF-R-expression as UVB or the PAF-R agonist, carbamoyl PAF (CPAF), both promote B16F10 tumor growth in wild-type (WT) mice, independent of whether B16F10 cells express PAF-Rs, but do not augment tumor growth in Pafr -/- mice. UVB-mediated augmentation of experimental murine tumor growth was inhibited with antioxidants, demonstrating the importance of Ox-GPC PAF-R agonists produced non-enzymatically. Host immune cells are required as CPAF-induced augmentation of tumor growth which is not seen in immunodeficient NOD SCID mice. Finally, depleting antibodies against IL-10 in WT mice or depletion of CD25-positive cells in FoxP3(EGFP) transgenic mice block UVB and/or CPAF-induced tumor growth supporting a requirement for IL-10 and Tregs in this process. These findings indicate that UVB-generated Ox-GPCs with PAF-R agonistic activity enhance experimental murine melanoma tumor growth through targeting host immune cells, most notably Tregs, to mediate systemic immunosuppression.

BACKGROUND: Hepatocellular carcinoma (HCC) is increasing in incidence due to hepatitis C. Stereotactic body radiotherapy (SBRT) is a noninvasive, effective therapy in the management of liver malignancies. The authors evaluated radiological response in 26 patients with HCC treated with SBRT at Indiana University. METHODS: Between March 2005 and June 2008, 26 patients with HCC who were not surgical candidates were enrolled in a phase 1 to 2 trial. Eligibility criteria included solitary tumors ≤ 6 cm or up to 3 lesions with sum diameters ≤ 6 cm, and well-compensated cirrhosis. All patients had imaging before, at 1 to 3 months, and every 3 to 6 months after SBRT. RESULTS: Patients received 3 to 5 fractions of SBRT. Median SBRT dose was 42 Gray (Gy) (range: 24-48 Gy). Median follow-up was 13 months. Per Response Evaluation Criteria in Solid Tumors (RECIST), 4 patients had a complete response (CR), 15 had a partial response (PR), and 7 achieved stable disease (SD) at 12 months. One patient with SD experienced progression marginal to the treated area. The overall best response rate (CR + PR) was 73%. In comparison, by European Association for the Study of the Liver (EASL) criteria, 18 of 26 patients had ≥ 50% nonenhancement at 12 months. Thirteen of 18 demonstrated 100% nonenhancement, being > 50% in 5 patients. Kaplan-Meier 1- and 2-year survival estimates were 77% and 60%, respectively. CONCLUSIONS: SBRT is effective therapy for patients with HCC with an overall best response rate (CR + PR) of 73%. Nonenhancement on imaging, a surrogate for ablation, may be a more useful indicator than size reduction in evaluating HCC response to SBRT in the first 6 to 12 months, supporting EASL criteria. Cancer 2012;118: 3191–98. © 2011 American Cancer Society.

Atopic dermatitis (AD) is a pruritic, chronic inflammatory skin disease that affects 10-20% of children and 1-3% of adults worldwide. Recent studies have indicated that the ability of Th2 cytokines, such as interleukin-4 (IL-4) to regulate skin barrier function may be a predisposing factor for AD development. The present studies examined the ability of increased Th2 activity to affect cutaneous barrier function in vivo and epidermal thickening. Mice that express a constitutively active Signal Transducer and Activator of Transcription 6 (STAT6VT) have increased Th2 cells and a predisposition to allergic inflammation were used in these studies, they demonstrate that topical treatment with the irritant sodium lauryl sulfate (SLS) caused increased transepidermal water loss and epidermal thickening in STAT6VT mice over similarly treated wild-type mice. The proliferation marker Ki-67 was increased in the epidermis of STAT6VT compared to the wild-type mice. However, these differences do not appear to be linked to the addition of an irritant as control-treated STAT6VT skin also exhibited elevated Ki-67 levels, suggesting that the increased epidermal thickness in SLS-treated STAT6VT mice is primarily driven by epidermal cell hypertrophy rather than an increase in cellular proliferation. Our results suggest that an environment with increased Th2 cytokines results in abnormal responses to topical irritants.

Purpose. The purpose was to compare three methods of predicting the gastric tube insertion length in children 1 month to 17 years of age: age-related, height-based (ARHB); nose-ear-xiphoid (NEX); and nose-ear-mid-umbilicus (NEMU). Design and Methods. The design was a randomized controlled trial. Children were randomly assigned to the ARHB, NEX, or NEMU groups. Tubes placed high were considered to be misplaced. Results. There were significant differences in percentages of correctly placed tubes, with ARHB and NEMU being more accurate than NEX. Practice Implications. NEX should no longer be used as a gastric tube insertion-length predictor. Either ARHB or NEMU should be used.

Objectives The purposes of this 36-month study of children with first recognized seizures were: (1) to describe baseline differences in behavior problems between children with and without prior unrecognized seizures; (2) to identify differences over time in behavior problems between children with seizures and their healthy siblings; (3) to identify the proportions of children with seizures and healthy siblings who were consistently at risk for behavior problems for 36 months; and (4) to identify risk factors for behavior problems 36 months following the first recognized seizure. Risk factors explored included demographic (child age and gender, caregiver education), neuropsychological (IQ, processing speed), seizure (epileptic syndrome, use of antiepileptic drug, seizure recurrence), and family (family mastery, satisfaction with family relationships, parent response) variables. Methods Participants were 300 children aged 6 through 14 years with a first recognized seizure and 196 healthy siblings. Data were collected from medical records, structured interviews, self-report questionnaires, and neuropsychological testing. Behavior problems were measured using the Child Behavior Checklist and the Teacher's Report Form. Data analyses included descriptive statistics and linear mixed models. Results Children with prior unrecognized seizures were at higher risk for behavior problems at baseline. As a group, children with seizures showed a steady reduction in behavior problems over time. Children with seizures were found to have significantly more behavior problems than their siblings over time, and significantly more children with seizures (11.3%) than siblings (4.6%) had consistent behavior problems over time. Key risk factors for child behavior problems based on both caregivers and teachers were: less caregiver education, slower initial processing speed, slowing of processing speed over the first 36 months, and a number of family variables including lower levels of family mastery or child satisfaction with family relationships, lower parent support of the child's autonomy, and lower parent confidence in their ability to discipline their child. Conclusions Children with new-onset seizures who are otherwise developing normally have higher rates of behavior problems than their healthy siblings; however, behavior problems are not consistently in the at-risk range in most children during the first 3 years after seizure onset. When children show behavior problems, family variables that might be targeted include family mastery, parent support of child autonomy, and parents’ confidence in their ability to handle their children's behavior.

Advances in breast cancer treatment have resulted in improved survival rates and concomitant reports of chemotherapy-related cognitive dysfunction. Music cognition, a form of general cognition, also may be negatively affected by chemotherapy. Moreover, chemotherapy may have general ototoxic effects. The goal of this study was to explore whether breast cancer survivors (BCS) had similar hearing thresholds and music cognition abilities compared with age-matched healthy controls (HC). A total of 56 women (28 BCS and 28 HC) completed the audiometric tests and the Montreal Battery Evaluation of Amusia (MBEA). Results indicate the 2 groups have similar hearing thresholds. A comparison of music cognition variables suggests possible differences in some music cognition tasks, with HC scoring slightly, but not significantly, better in melodic perception. The BCS scored slightly better, though not significantly, on melodic memory. An adequately powered study including cognitive variables is needed for verification of findings and to establish clinical meaningfulness.

As primary caregivers of children with mental health problems, mothers face challenges that put them at risk for depression, which is rarely identified or addressed. The aims of this paper were to (a) identify mean differences among demographic, stressor, threat, and resource variables specified in a theoretical model and thought to be associated with maternal depressive symptoms and (b) determine how much variability in depressive symptoms is explained by these variables. High levels and prevalence of depressive symptoms were found within a quality of life study that these data were drawn from. Of 139 mothers participating in this study, 58% had a score of 16 or greater on the CES-D indicating moderate to high levels of depressive symptoms. Significant differences were found between mothers with higher versus lower levels of depressive symptoms for 11 of the 18 variables. Hierarchical regression was used to examine the variance explained in depressive symptoms based upon the conceptual model with 4 composite variables. Income (step 1), behavioral problems (step 2), threat appraisal (step 3), and resource appraisal (step 4) combined explained 42% of the variance.

Purpose: Lymphedema is a significant long-term complication of primary therapy for breast cancer. VEGF has a major impact on vascular permeability and lymphangiogenesis. In a prior case control study, we found a significant increase in serum VEGF-C (median 6895 vs. 5349 pg/mL, p=0.0016) in women with lymphedema compared to women without lymphedema suggesting inhibition of VEGF-C as a potential therapeutic strategy. Methods: Pts with significant unilateral lymphedema were treated with pazopanib 800 mg/day continuously. Baseline assessments include arm volume, interstitial fluid pressure (IFP), extracellular fluid volume by lymphometer (ECF), quality of life (QOL) and plasma VEGF-C,-D, and R3. IFP was measured serially for 24 hours after the first treatment; arm volume, ECF, QOL, and plasma VEGF-C/D/R3 are assessed every 4 weeks. Results: Ten pts were enrolled. Median duration of lymphedema was 3.5 years (0.7-8.2) Median time since surgery was 5.1 years (1.0-14.2); median time since radiation (n=9) was 4.7 years (0.4-8.8). Complete IFP data are available in 7 pts. Baseline IFP was significantly higher in the affected compared to unaffected arm (mean 5.73 vs. -1.78 mmHg; p=0.0005). Mean IFP in the affected arm decreased an average of 76% 24 hours after initiation of pazopanib (5.73 vs. 1.56 mmHg; p=0.0061). Toxicity was greater than anticipated with grade 3 fatigue (n=3), arthralgia (n=2), and anorexia (n=1); three pts discontinued therapy prior to the first post-treatment assessment. Five pts met the definition of response with a ≥25% reduction in excess arm volume four weeks after initiating treatment. ECF significantly (p=0.014) decreased as well though the mean difference in excess arm volume did not significantly change (p=0.06). Conclusions: Preliminary data supports the hypothesis that VEGF plays a role in the development and/or persistence of lymphedema after local therapy for breast cancer. Pazopanib acutely decreases IFP, leading to a decrease in ECF and modest improvement in arm volume but results in significant toxicity at the dose used on this study. Subsequent studies will explore a lower dose of pazopanib in this population. This study was supported by the Breast Cancer Research Foundation with pazopanib supplied by GSK. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P2-14-02.

Objectives Children with long-standing epilepsy have a significantly increased risk of academic underachievement compared with healthy controls. We prospectively followed children from seizure onset to assess the relationship between change in neuropsychological functioning and change in academic achievement and to explore the risk and protective moderating effects of demographic, seizure, and family variables. Methods As part of a larger study, neuropsychological and academic data were collected at both baseline and 36 months for 219 children 6–14 years of age with seizures. Prior factor analysis of results from a battery of well-standardized neuropsychological tests yielded four factors: language, processing speed, attention/executive/construction, and verbal memory/learning. Academic achievement was measured with the Woodcock–Johnson Revised Achievement Test Battery. Correlation coefficients and linear mixed models were used for analysis. Results The reading and math scores of children with seizures and siblings did not differ at baseline, but children with seizures had lower scores than siblings at 36 months. Writing scores were significantly lower for affected children than siblings at both times. Among children with seizures, there were positive correlations between neuropsychological functioning and academic achievement at baseline and 36 months. Changes in language and in verbal memory/learning were positively correlated with change in reading achievement ( r = 0.25 and r = 0.17, respectively). Age at onset moderated the association between change in neuropsychological functioning and change in reading and writing achievement ( P ≤ 0.006), with stronger relationships among younger children (β = 0.25–0.44). The association between change in language and change in writing achievement was moderated by caregiver anxiety ( P = 0.04; stronger for more anxious parents, β = 0.40), and the association between change in processing speed and change in math achievement was moderated by etiology ( P = 0.02; stronger for symptomatic/cryptogenic vs idiopathic, β = 0.29). Gender and other family variables did not have significant moderating effects. Conclusions Changes in neuropsychological function were associated with changes in academic achievement following onset of seizures, with risk factors being younger age at onset, lower caregiver education, high parental anxiety, and symptomatic/cryptogenic etiology. Academic performance should be closely monitored in children with early-onset seizures.

Epithelial ovarian cancer (OC) is the most lethal gynecologic malignancy. The majority of advanced stage patients develop uniformly fatal resistance to standard platinum-based treatments. Epigenetic changes, particularly DNA methylation aberrations have been implicated in acquired resistance to platinum in OC. The goal of the current study was to identify methylation changes associated with the development of acquired resistance to platinum-based chemotherapy. We hypothesized that OC tumors harboring an aberrant DNA methylome could be reversed by DNMTi and re-sensitized to platinum treatment. To achieve our objective, we generated and compared tumor DNA methylation profiles from patients with recurrent platinum-resistant OC treated on a clinical trial with a DNA methyl transferase inhibitor, guadecitabine, before (n=65) and after (n=19) treatment (NCT01696032), and patients with primary (platinum-naïve) OC (n=20). Human ovarian surface epithelial cells (HOSE) were used as controls (n=5). We examined methylation levels across the genome using the Infinium Human Methylation 450 Bead Chip (Illumina). By comparing the methylome of platinum naive and platinum resistant ovarian tumors, normalized to HOSE, we identified 444 CpG island-containing gene promoters that became hypermethylated in resistant tumors. Of those, 45 gene promoters were hypermethylated at an FDR0.1. Among those significantly hypermethylated genes, acquired promoter CpG island methylation of Ras Association Domain Family 1A (RASSF1A; a tumor suppressor gene in multiple cancer types) was observed. Of the 444 hypermethylated promoters in tumor resistant samples, 93 CpG islands became hypomethylated after guadecitabine treatment, suggesting that these promoters may be associated with reversal of resistance. Of those were the IFNA8 promoter, a gene known to be associated with anti-tumor effects in ovarian and other solid malignancies, and DEFB124, which is involved in the innate immune response. Pathways associated with immune reactivation were highly enriched by guadecitabine treatment, including IL-12 signaling and production of macrophages and MAPK and apoptosis signaling. Together, these results support that aberrant DNA methylation affecting gene networks associate with immune response plays a role in platinum resistant development and could be a therapeutic target. Citation Format: Fang Fang, Horacio Cardenas, Guanglong Jiang, Susan M. Perkins, Chi Zhang, Harold Keer, Yunlong Liu, Daniela Matei, Kenneth Nephew. Epigenomic signatures of acquired platinum resistance in high grade serous ovarian cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2997.

Background: Identifying methods to accurately measure the glomerular filtration rate (GFR) in obese individuals without kidney overt kidney disease is necessary to understanding the pathophysiology and natural history of obesity-related kidney disease. Methods: Using a cross-sectional design, iohexol clearance and disposition was measured, an optimal sampling schedule was identified, and the reliability of GFR-estimating methods was described in 29 obese individuals with normal serum creatinine levels. Iohexol disposition was measured using population pharmacokinetics. The agreement with GFR-estimating equations was assessed by intraclass coefficients. Results: Mean age was 44 ± 10 years, body mass index 45 ± 10, creatinine 0.7 ± 0.2 mg/dl (62 ± 18 µmol/l) , and cystatin C 0.83 ± 0.18 mg/dl (8.3 ± 1.8 mg/l). Iohexol disposition fit a two-compartment model and 5 sampling windows were identified over a 4-hour period to optimize model accuracy and minimize blood draws. Precision was not compromised with this sampling design. Neither creatinine nor cystatin C were linearly correlated with the measured GFR though cystatin C was independent of body composition. Agreement was fair to poor between the measured GFR and GFR-estimating equations. Conclusion: This study offers a rigorous method to study obesity-related kidney disease and improve upon suboptimal GFR-estimating methods.

8513Background: For pts with resectable stage IIIA NSCLC, one accepted tx option is induction therapy with concurrent chemoradiation followed by surgical resection in selected pts. However, the app...

e16567Background: Assessment of TP using 62Cu-ETS PET/CT has been demonstrated in pts with RCC (Fletcher et al, J Nuc Med 2015; 56:56-62, Logan et al, ASCO 2014; abstr 11110) compared to 15O-water ...

4118Background: Chemotherapy and surgical resection improve survival in patients with PDAC. Neoadjuvant therapy (NAT) may allow better selection for resection and provides early treatment of microm...

e16545Background: Preclinical data suggests platinum resistant embryonal carcinoma (EC) cell lines are sensitive to hypomethylating agents. Guadecitabine (G), a novel hypomethylating dinucleotide o...

Background Patients with chronic heart failure (HF) have cognitive deficits in memory, psychomotor speed, and executive function and poor health-related quality of life (HRQL), but the association between cognitive deficits and HRQL is unknown. Objectives The objectives of this study were to (1) evaluate the relationship between HF severity, age, comorbidities, and cognitive deficits and HRQL among patients with chronic HF and (2) examine whether cognitive deficits mediated the relationship between HF severity and HRQL. Design and sample This study was part of a larger explanatory study; 249 patients with HF completed face-to-face interviews. Methods Measures of HF severity, comorbidity (multiple comorbid conditions, hypertension, and depressive symptoms), cognitive function (domains of language, working memory, memory, psychomotor speed, and executive function), and HRQL were obtained. Clinical variables were abstracted from patients' records. Statistical analyses were conducted using descriptive statistics, Pearson correlation coefficients, and multiple linear regression analyses. Results Overall, the HRQL of patients was moderately poor. Heart failure severity, age, depressive symptoms, and total recall memory explained 55% of the variance in HRQL, but the contribution of memory was minimal (1%). Patients with more severe HF, younger age, and more depressive symptoms had poorer HRQL. Other cognitive function variables, multiple comorbidity, and hypertension were not significant explanatory variables for HRQL. Cognitive deficits did not mediate the relationship between HF severity and HRQL. Conclusions Novel interventions targeted at improving HRQL continue to be urgently needed, particularly among younger patients and patients with depressive symptoms. Measures of HRQL are not sufficient as outcomes when investigating cognitive deficits in HF. Investigators need to include outcome measures of patients' actual abilities to perform daily activities and HF self-care.

Summary Purpose: To test over time the relationships of neuropsychological functioning to mental health in children following a first recognized seizure and, of primary importance, to determine if the strength of these relationships differs based on risk and protective factors. Methods: In a larger prospective study, 135 children with a first seizure (ages 8–14 years) and 73 healthy sibling controls completed neuropsychological testing at baseline and 36 months. Structured telephone interviews were used to obtain data from children on mental health and family environment; major caregiving parents provided data on demographic and family variables. Data analyses included correlation coefficients and linear regression models. Results: Children with seizures showed an overall trend for improvement in mental health. More children with seizures than siblings had declines in processing speed. Declines in neuropsychological functioning were correlated with worse mental health. With regard to risk and protective factors, higher parent education protected against decline in self-esteem related to decline in processing speed. Better family functioning and greater parental support protected against decline in self-esteem related to decrease in verbal memory and learning. Older child age protected against increase in depressive symptoms related to decline in processing speed. Discussion: Seizure onset had a negative impact on mental health in children with declines in cognitive functioning except for older children and those with more family resources. Children should be assessed for declines in processing speed and, if found, those subgroups of children with less educated or more anxious parents and those in less supportive families should be targeted for interventions.

► Background: Patients with heart failure (HF) have been found to have cognitive deficits, but it remains unclear whether these deficits are associated with HF or with aging or comorbid conditions common in HF. ► Objectives: The purpose of this study was (a) to determine the types, the frequency, and the severity of cognitive deficits among patients with chronic HF compared with age-and education-matched healthy participants and participants with major medical conditions other than HF, and (b) to evaluate the relationships between HF severity, age, and comorbidities and cognitive deficits. ► Methods: A sample of 414 participants completed the study (249 HF patients, 63 healthy and 102 medical participants). The HF patients completed measures of HF severity, comorbidity (multiple comorbidity, depressive symptoms), and neuropsychological functioning. Blood pressure and oxygen saturation were assessed at interview; clinical variables were abstracted from records. Participants in the comparison groups completed the same measures as the HF patients except those specific to HF. ► Results: Compared with the healthy and medical participants, HF patients had poorer memory, psychomotor speed, and executive function. Significantly more HF patients (24%) had deficits in three or more domains. Higher (worse) HF severity was associated with more cognitive deficits; HF severity interacted with age to explain deficits in executive function. Surprisingly, men with HF had poorer memory, psychomotor speed, and visuospatial recall ability than women. Multiple comorbidity, hypertension, depressive symptoms, and medications were not associated with cognitive deficits in this sample. ► Discussion: HF results in losses in memory, psychomotor speed, and executive function in almost one fourth of patients. Patients with more severe HF are at risk for cognitive deficits. Older patients with more severe HF may have more problems in executive function, and men with HF may be at increased risk for cognitive deficits. Studies are urgently needed to identify the mechanisms for the cognitive deficits in HF and to test innovative interventions to prevent cognitive loss and decline.

TPS179 Background: Unresectable stage III NSCLC demonstrates poor 5-yr OS outcomes. The current standard of care for fit patients in this setting is concurrent chemoradiation. Previous studies evaluating the addition of induction or consolidation chemotherapy, EGFR-targeted agents, ant-angiogenic agents, and higher doses of radiation have failed to definitively improve OS over chemoradiation alone. Recently, a trial of consolidation PD-L1 inhibition demonstrated improved PFS over chemoradiation alone, and a second trial of consolidation PD-1 inhibition is awaiting data maturation. This may herald a change to the standard of care in this setting. The addition of CTLA-4 inhibition to anti-PD-1 monoclonal antibodies has shown improved OS in melanoma and has demonstrated encouraging early phase data in stage IV NSCLC. Therefore, we initiated a trial evaluating the addition of a CTLA-4 inhibitor to PD-1 inhibition for consolidation treatment of unresectable stage III NSCLC. Methods: This is a multi-center, randomized, phase II study of nivolumab or the combination of nivolumab and ipilimumab as consolidation therapy following concurrent chemoradiation in unresectable stage III NSCLC. Patients will receive concurrent chemoradiation with one of three standard chemotherapy backbones (Cis-Etop, Cis-Pem, or Carbo-Pac), and repeat imaging will be done 4-8 weeks following completion of therapy. Patients without progressive disease will be randomized 1:1 to receive either niv 480mg IV every 4 weeks or the combination of niv 3mg/kg IV every 2 weeks and ipi 1mg/kg IV every 6 weeks for up to 6 months. The trial will enroll a total of 108 patients with 54 in each arm. The two arms are non-comparator arms and will be compared with historical controls. The primary endpoint is the improvement of PFS at 18 months, and key secondary endpoints include OS and the toxicity of consolidation niv and niv/ipi. Exploratory endpoints will look at the correlation between multiple clinical, radiographic, and laboratory parameters and outcomes, as well as the association of these parameters with the development of pneumonitis. This trial opened to accrual in September 2017. Clinical trial information: NCT03285321.

TPS194 Background: The standard of care for locally advanced esophageal adenocarcinoma is concurrent chemoradiation (CRT) followed by esophagectomy with lymphadenectomy. Approximately 30% of patients achieve a complete pathologic response (pCR) with this multimodality approach, which has been correlated with improved disease-free survival. The risk of relapse in the remaining 70% of patients who have pathologic evidence of persistent disease in the surgical specimen is extremely high and estimated at 60-70%. Preclinical studies have demonstrated that radiation with or without concurrent chemotherapy upregulates the programmed cell death receptor- 1 (PD-1) pathway by inducing a local inflammatory response, an effect that persists for a number of months after cessation of therapy. Durvalumab is a selective, high affinity, engineered human IgG1 monoclonal antibody that blocks PD-L1 binding to PD-1 and CD80, and has shown activity in metastatic esophageal cancer. The aim of this study is to evaluate efficacy of post-operative durvalumab with respect to decreasing the relapse rate in patients who do not achieve pCR following CRT. Methods: Patients with esophageal adenocarcinoma who have pathologic evidence of persistent disease in the surgical specimen following neoadjuvant concurrent CRT (carboplatin plus paclitaxel or cisplatin plus 5-FU) and R0 resection are eligible for enrollment on this single arm phase II study. Durvalumab 1500mg IV every 4 weeks is started within 1-3 months of surgery and continued for up to 1 year. The primary endpoint is 1-year relapse free survival (RFS). Secondary endpoint is to assess the incidence and severity of overall and treatment related adverse events. Exploratory endpoints include PDL1 expression in tumor and tumor infiltrating lymphocytes, assessment of Immunoscore within the center and invasive margin of the tumor, and the correlation between changes in circulating tumor cell numbers in response to PD-L1 inhibition. The study is currently open to accrual at 5 sites in the Big Ten Cancer Research Consortium and 17 of the planned 23 patients have been enrolled within the past 14 months. Clinical trial information: NCT02639065.

Background and purpose We report frequency of brachial plexopathy in early-stage non-small cell lung cancer treated with stereotactic body radiotherapy. Materials and methods 276 T1–T2, N0 or peripheral T3, N0 lesions were treated in 253 patients with stereotactic radiotherapy at Indiana University and Richard L. Roudebush VAMC from 1998 to 2007. Thirty-seven lesions in 36 patients were identified as apical lesions, defined as epicenter of lesion superior to aortic arch. Brachial plexus toxicity was scored for these apical lesions according to CTCAE v. 3.0 for ipsilateral shoulder/arm neuropathic pain, motor weakness, or sensory alteration. Results The 37 apical lesions (19 Stage IA, 16 IB, and 2 IIB) were treated with stereotactic body radiotherapy to a median total dose of 57Gy (30–72). The associated brachial plexus of 7/37 apical lesions developed grade 2–4 plexopathy (4 pts – grade 2, 2 pts – grade 3, 1 pt – grade 4). Five patients had ipsilateral shoulder/arm neuropathic pain alone, one had pain and upper extremity weakness, and one had pain progressing to numbness of the upper extremity and paralysis of hand and wrist. The median of the maximum brachial plexus doses of patients developing brachial plexopathy was 30Gy (18–82). Two-year Kaplan–Meier risk of brachial plexopathy for maximum brachial plexus dose >26Gy was 46% vs 8% for doses ⩽26Gy ( p =0.04 for likelihood ratio test). Conclusions Stereotactic body radiotherapy for apical lesions carries a risk of brachial plexopathy. Brachial plexus maximum dose should be kept

We have previously demonstrated that the EP1 subtype of PGE2 receptor is expressed in the differentiated compartment of normal human epidermis and is coupled to intracellular calcium mobilization. We therefore hypothesized that the EP1 receptor is coupled to keratinocyte differentiation. In in vitro studies, radioligand binding, RT-PCR, immunoblot and receptor agonist-induced second messenger studies demonstrate that the EP1 receptor is up-regulated by high cell density in human keratinocytes and this up-regulation precedes corneocyte formation. Moreover, two different EP1 receptor antagonists, SC51322 and AH6809, both inhibited corneocyte formation. SC51322 also inhibited the induction of differentiation-specific proteins, cytokeratin K10 and epidermal transglutaminase. We next examined the immunolocalization of the EP1 receptor in non-melanoma skin cancer in humans. Well differentiated SCCs exhibited significantly greater membrane staining, while spindle cell carcinomas and BCCs had significantly decreased membrane staining compared with normal epidermis. This data supports a role for the EP1 receptor in regulating keratinocyte differentiation.

Few studies have utilized both categorical and dimensional measures of psychopathology in children with epilepsy. We evaluated 173 children (88 males, 85 females; mean age 11.7y [SD 1.8]; range 9-14y) who had epilepsy (generalized 36%, partial 61%) for at least 6 months. The primary caregiver completed a dimensional measure, the Child Behavior Checklist (CBCL), and a categorical measure, either the Child Symptom Inventory (CSI) or the Adolescent Symptom Inventory (ASI). Correlation coefficients were computed between the CBCL scores and CSI/ASI symptom scores. For all children, diagnostic risk was higher than norms on CSI/ASI for attention-deficit-hyperactivity disorder (ADHD) inattentive type, ADHD combined type, oppositional defiant disorder, and dysthymic disorder. For children between 9 and 12 years, elevated scores were found on CBCL, total, internalizing, and attention problems, and on CSI, diagnostic risk for conduct disorder and Asperger syndrome. For children of 13 and 14 years, ASI diagnostic risk was higher for specific phobia, obsessions, posttraumatic stress disorder, motor tics, antisocial personality, panic attack, somatization disorder, and enuresis. CBCL and symptom scores on the CSI/ASI were significantly correlated. The conclusion was that children with epilepsy have high rates of behavioral difficulties on both dimensional and categorical measures. Concurrent validity for the CSI/ASI was supported.

This study characterized structural abnormalities associated with onset of seizures in children, using magnetic resonance imaging and a standardized classification system in a large prospective cohort. Two hundred eighty-one children aged 6-14 years completed magnetic resonance imaging within 6 months of their first recognized seizure. Most examinations were performed with a standardized, dedicated seizure protocol; all were scored using a standard scoring system. At least one magnetic resonance imaging abnormality was identified in 87 of 281 (31%) children with a first recognized seizure. Two or more abnormalities were identified in 34 (12%). The commonest abnormalities were ventricular enlargement (51%), leukomalacia/gliosis (23%), gray-matter lesions such as heterotopias and cortical dysplasia (12%), volume loss (12%), other white-matter lesions (9%), and encephalomalacia (6%). Abnormalities defined as significant, or potentially related to seizures, occurred in 40 (14%). Temporal lobe and hippocampal abnormalities were detected at a higher frequency than in previous studies (13/87). Magnetic resonance imaging and a standardized, reliable, valid scoring system demonstrated a higher rate of abnormal findings than previously reported, including findings formerly considered incidental. Practice parameters may need revision, to expand the definition of significant abnormalities and support wider use of magnetic resonance imaging in children with newly diagnosed seizures.

SUMMARY Purpose: To define seizure recurrence rates in normal children who had had a single seizure and to define electroencephalography (EEG) or magnetic resonance imaging (MRI) utility in predicting seizure recurrence. Methods: We studied 150 children (6 to 14 years) with a first afebrile, unprovoked seizure. Inclusion criteria were: Normal physical and neurological examination, undergone EEG and MRI studies of the brain, and followed for at least 27 months. These children participated in an ongoing prospective study of new onset seizures in childhood. Results:The seizure recurrence rate was 66.4%. An abnormal EEG had no association with seizure recurrence at 9, 18, or 27 months (p ¼ 0.1806, p ¼ 0.2792, and p ¼ 0.2379, respectively). A ‘‘significant’’ MRI abnormality, which occurred in 16.0% of patients, was associated with an increased seizure recurrence risk at 9 months (p ¼ 0.0389) but not at 18 or 27 months. Discussion: EEG findings poorly predict recurrence after a single seizure. The high rate of MRI abnormalities suggests that MRI may need consideration as a routine test to evaluate epilepsy in normal children.

The aims of this study were to develop an instrument to measure parents' responses and perceptions related to the onset of either seizures or asthma in a child (aged 4-14) and to assess the initial reliability and validity of the instrument. The 35-item scale developed comprised five subscales: Child Support, Family Life/Leisure, Condition Management, Child Autonomy, and Child Discipline. Subjects were parents of 224 children with new-onset seizures and 104 parents of children with new-onset asthma. Internal consistency reliabilities were stronger for Child Support, Family Life/Leisure, and Condition Management than for Child Autonomy and Child Discipline for both samples. Test-retest reliability ranged from good to fair for both samples. The associations between parent positive mood and all of the subscales for both samples in the predicted directions provided key empirical support for validity. The scale has potential for use in research and in the clinical setting. In addition, the scale has potential to be used with other conditions.

Little is known about the bases of parental worry about adolescents' risk for acquiring a sexually transmitted infection (STI). Parents ( N = 247) of adolescents 12—17 years endorsed reasons that explained their worry or nonworry. Parents' past experience of an STI, perception of the child's sexual activity, and racial self-identification were predictors of worry. Cluster analyses identified five groups of worriers and four groups of nonworriers. Worriers tended to select reasons reflecting an external parental locus of control or child-specific reasons. Nonworriers endorsed reasons consistent with internal parental locus of control. Findings suggest that preventive health communication should be tailored to parents' perceptions of risk and protective factors.

Objective To evaluate the acceptability to Latino parents of having their adolescent children vaccinated against sexually transmitted infections, and to identify potential demographic correlates of acceptability. Methods We applied established methodology to a sample of 119 Latino parents who accompanied their children (51% female, aged 12–17 years) to medical appointments. The parents used computer-based questionnaires to rate 9 hypothetical vaccine scenarios. The scenarios had 4 dimensions: mode of transmission (sexually transmitted or not sexually transmitted), severity of infection (curable, chronic, or fatal), vaccine efficacy (50%, 70%, or 90%), and availability of behavioral methods for prevention (available or not available). Willingness by parents to vaccinate their adolescents under each vaccine scenario was assessed on a scale (range, 0–100). Conjoint analysis was used to determine the relative contribution of each dimension to the ratings. Results The study sample consisted of predominantly Mexican immigrant parents, 94% of whom chose to complete the Spanish version of the computerized interview. The mean value of the parents' willingness to accept vaccination for their adolescent children was exceptionally high. For example, the mean score of the Latino parents for the 6 sexually transmitted infection (STI) vaccine scenarios (score 86.2; SD 21.1) was far higher than the mean score in previous studies (81.3, SD 21.1). Conjoint analysis revealed that the dimensions of vaccine efficacy and severity of infection were equal in terms of their influence on vaccine ratings for the Latino parents. The next most influential dimension on vaccine ratings was the availability of behavioral prevention, followed by the sexual transmissibility of the infection. Conclusions Our sample of predominantly Mexican parents was accepting of the concept of STI vaccination for their adolescent children. Important issues for parents include vaccine efficacy and severity of infection, followed by vaccines for infections that had no method of behavioral prevention available. Overall, there is little difference in the relative preference of a STI versus non-STI vaccine for their adolescent children.

Background The treatment of primary mediastinal nonseminomatous germ cell tumors (PMNSGCT) with cisplatin-based chemotherapy, followed by surgical resection of residual disease, has been established. We reviewed our institution's 25-year experience in the cisplatin era to determine surgical risks and predictors of survival after surgery for PMNSGCT. Methods A total of 158 patients (mean age, 29 ± 8 years) who underwent postchemotherapy operations for PMNSGCT were reviewed and multiple variables analyzed. Results Ten (6%) operative deaths occurred, nine of which were attributed to respiratory failure, and 26 (18%) patients experienced postoperative complications, including 9 with respiratory failure. None of 17 recent patients who received chemotherapy regimens that did not contain bleomycin experienced pulmonary complications ( p = 0.12 vs patients who received bleomycin). Operative survivors were followed up a median of 34 months (range, 1 to 194 months). Multivariable analysis demonstrated that the postchemotherapy pathologic category of complete necrosis vs teratoma), persistent germ cell or nongerm cell cancer, and elevated serum tumor markers after operation were independently predictive of survival. Conclusions Operative risks for PMNSGCT appear to be improved with the use of chemotherapy regimens that do not contain bleomycin. Patients pathologically demonstrating complete tumor necrosis in the residual mass after chemotherapy have excellent long-term survival, with decreasing survival after resection of teratoma and persistent germ cell or nongerm cell cancer. Patients pathologically demonstrating persistent germ cell or nongerm cell cancer have poor but possible long-term survival, which justifies an aggressive surgical approach in patients who are deemed operable.

BACKGROUND Metastatic testicular tumors that have not been successfully treated by means of initial chemotherapy are potentially curable with salvage chemotherapy. METHODS We conducted a retrospective review of 184 consecutive patients with metastatic testicular cancer that had progressed after they received cisplatin-containing combination chemotherapy. We gave 173 patients two consecutive courses of high-dose chemotherapy consisting of 700 mg of carboplatin per square meter of body-surface area and 750 mg of etoposide per square meter, each for 3 consecutive days, and each followed by an infusion of autologous peripheral-blood hematopoietic stem cells; the other 11 patients received a single course of this treatment. In 110 patients, cytoreduction with one or two courses of vinblastine plus ifosfamide plus cisplatin preceded the high-dose chemotherapy. RESULTS Of the 184 patients, 116 had complete remission of disease without relapse during a median follow-up of 48 months (range, 14 to 118). Of the 135 patients who received the treatment as second-line therapy, 94 were disease-free during follow-up; 22 of 49 patients who received treatment as third-line or later therapy were disease-free. Of 40 patients with cancer that was refractory to standard-dose platinum, 18 were disease-free. A total of 98 of 144 patients who had platinum-sensitive disease were disease-free, and 26 of 35 patients with seminoma and 90 of 149 patients with nonseminomatous germ-cell tumors were disease-free. Among the 184 patients, there were three drug-related deaths during therapy. Acute leukemia developed in three additional patients after therapy. CONCLUSIONS Testicular tumors are potentially curable by means of high-dose chemotherapy plus hematopoietic stem-cell rescue, even when this regimen is used as third-line or later therapy or in patients with platinum-refractory disease.

Structural brain abnormalities of various types can lead to epilepsy, and many are associated with delays in cognitive development or specific cognitive deficits. Genetic cortical malformations (e.g., lissencephaly, schizencephaly, heterotopias, and polymicrogyria) are often characterized by seizure disorders, typically with significant delays in broad cognitive development (Guerrini, 2005). Similarly, tuberous sclerosis is characteristically associated with seizures and developmental delays. More importantly, the degree of intellectual deficit appears to be related to the degree of structural abnormality (i.e., the number of tubers) (Jambaque et al., 1991). Hippocampal sclerosis, a common finding in temporal lobe epilepsy in adults, has been associated with specific deficits in verbal memory and language or spatial memory in a manner consistent with the hemisphere affected (e.g., Baxendale et al., 1998); intelligence and other functions are relatively spared (e.g., Bourgeois et al., 1983; Ellenberg et al., 1986; Martin et al., 1999; Rodin et al., 1986). The degree of neuropsychological deficit is related to hippocampal volumes in adulthood (Baxendale et al., 1998; Hermann et al., 2002). The nature and extent of these neuropsychological deficits appear to be related to age of seizure onset, with lower memory scores and smaller hippocampal volumes observed among individuals with childhood onset (Baxendale et al., 1998). Furthermore, these effects might even be moderated by age of onset, with earlier age of onset being associated with not only hippocampal volume loss but an additional reduction in total brain volume, together with broader neuropsychological deficits that extend outside of the memory domain (Hermann et al., 2002). These findings support an association between the presence of structural brain abnormalities and cognitive deficits in children with epilepsy. For some conditions (e.g. tuberous sclerosis complex), the extent of the structural abnormalities is related to the severity of neuropsychological dysfunction (Jambaque et al., 1991; O’Callaghan et al., 2003; Weber et al., 2000). Moreover, the type and location of the structural abnormalities can be related to the nature of neuropsychological deficits affecting specific cognitive domains (e.g., Hermann et al., 2002). Shinnar and colleagues followed 411 children in New York City after their first unprovoked afebrile seizure (Shinnar et al., 2001). That study helped to characterize a new onset sample with regard to structural brain abnormalities; however, there are potential limitations that could affect the conclusions and generalizability of those findings. First, although the sample was large, only 27% (n = 59) of the children had MRIs; the majority (73%) had CT scans. As would be expected, abnormalities were detected in higher proportions of children using MRI (34%) compared to CT (22%). Therefore, that study likely underestimated the extent of structural brain abnormalities in this population. Second, there was no differentiation between abnormalities that seemed to be related to the seizure disorder versus those that were not related. In addition, imaging data were collected over the course of the children’s disorder in order to use the most sensitive imaging study for each participant that was available at the time of the 2001 publication (Shinnar, 2006). Consequently, many of the children in that sample completed their imaging studies many years after onset. In a subsequent and parallel study, Berg and colleagues followed 613 children in Connecticut following a second unprovoked seizure (Berg et al., 2000). The Connecticut study improved on many of the limitations in the New York City study. The majority of children in the Connecticut study completed MRI studies (vs. CT), and the imaging was obtained in conjunction with the initial evaluation at onset. Consequently, the lower proportion of children showing abnormalities in the Connecticut sample (12.7%, using more sensitive imaging but closer to onset) versus the New York City sample (21%, using less sensitive imaging but more chronic seizures) raises the possibility that some of these abnormalities might develop or become more detectable over the course of the disorder. However, it is possible that differences in exclusion criteria and/or definitions of onset also contributed to the differences in rates of abnormalities. In an effort to start addressing these differences, it would be beneficial to replicate these findings in a new sample with many of the strengths of the Connecticut study. All of these imaging studies have documented the potential for structural abnormalities at the onset of seizures in children. However, it is unclear if these abnormalities are related to cognitive function. Neuropsychological data were not reported for any of these studies. Neuropsychological deficits have been well documented in children with epilepsy (see Fastenau et al., 2003, for brief review), but there have been mixed findings in children at the onset of the disorder. Williams and colleagues (Williams et al., 1998) examined a small cohort (n = 37) of children newly diagnosed with epilepsy prior to initiation of antiepileptic drug therapy and found no differences in neuropsychological performance compared to children newly diagnosed with diabetes. However, others have documented subtle deficits at onset in children. Oostrom and colleagues (Oostrom et al., 2003) compared 51 children with new onset of epilepsy (i.e., at least two seizures) to a group of 48 healthy same age classmates with nearly identical IQ. At baseline they found that children with epilepsy showed deficits in attention and learning compared to the control group. None of these studies examined the relationship between structural abnormalities and neuropsychological deficits at the onset of the disorder. In this study, we explored the relationships between MRI abnormalities of the brain and neuropsychological functioning in children who were evaluated following their first recognized seizure. In the analyses we separated the MRI abnormalities into those that seemed to be related to the seizure disorder and into those that were not related.

The purpose of this study was to compare teachers' ratings of academic performance over 24 months between children with new-onset seizures (N=121) and those with new-onset asthma (N=54) aged 4 to 14. At each data collection point (baseline, 12 months, 24 months), children with seizures were placed into two groups according to their recurrent seizure status (yes/no) during that period. Longitudinal linear mixed models were used to explore differences between the asthma group and the two seizure groups and to determine if differences in teachers' ratings of performance in children with seizures were associated with age, gender, or use of medication. In the seizure sample, scores for children in both groups (with and without recurrent seizures) initially declined at 12 months; however, at 24 months, children who did not have recurrent seizures improved, whereas children who continued to have recurrent seizures declined. There was a trend for younger children to decline more than older children.

The classification of fibroepithelioma of Pinkus as basal cell carcinoma or trichoblastoma remains controversial. Immunohistochemical stains for androgen receptor may be useful in differentiating basal cell carcinoma from trichoepithelioma or trichoblastoma. We studied androgen receptor expression in 13 fibroepitheliomas of Pinkus, 11 basal cell carcinomas, 12 trichoepitheliomas, and 3 trichoblastomas. Androgen receptor expression was present in 77% (10/13) of fibroepitheliomas of Pinkus, 73% (8/11) of basal cell carcinomas, 17% (2/12) of trichoepitheliomas, and 0% (0/3) of trichoblastomas. Androgen receptor expression was significantly higher in fibroepitheliomas of Pinkus compared with trichoepitheliomas and trichoblastomas (P = .0007), but not basal cell carcinoma (P = 1.00). Tumor-associated Merkel cells, a feature of benign follicular tumors, was identified by cytokeratin 20 stains. Merkel cells were identified in 85% (11/13) of fibroepitheliomas of Pinkus, 27% (3/11) of basal cell carcinoma cases, and 73% (11/15) of benign follicular tumors. Cytokeratin 20 expression was significantly higher in fibroepithelioma of Pinkus and benign follicular tumors compared with basal cell carcinomas (P = 0.0111 and P = 0.025, respectively). No significant difference was found between fibroepitheliomas of Pinkus and trichoepitheliomas and trichoblastomas (P = 1.00). Similar to basal cell carcinomas, fibroepitheliomas of Pinkus express androgen receptors, potentially supporting classification as a basal cell carcinoma. Conversely, fibroepithelioma of Pinkus demonstrates retention of Merkel cells, a feature of benign follicular tumors. Immunophenotypic evidence for the classification of fibroepithelioma of Pinkus remains inconclusive. In small, partial biopsy specimens, coexpression of androgen receptor and cytokeratin 20 may aid in the diagnosis of fibroepithelioma of Pinkus.