Correlation Between Plasma Catecholamines, Weight, and Diabetes in Pheochromocytoma and Paraganglioma.

CONTEXT: Pheochromocytomas and paragangliomas (PCC/PGL) are neuroendocrine tumors with discrete catecholamine profiles that cause incompletely understood metabolic and physiologic changes. OBJECTIVE: The objective was to evaluate relationships between plasma catecholamines, body weight, and hemoglobin A1c (HbA1c). We hypothesized that individual catecholamines would correlate negatively with weight and glucose control. DESIGN: A retrospective cohort study was performed (1999-2020). Wilcoxon rank-sum tests compared nonparametric, continuous variables; mixed-effect linear modeling (MEM) evaluated relationships between catecholamines and weight or HbA1c. The median study duration was 54.2 months [interquartile range (IQR) 19.0-95.1]. SETTING: Tertiary academic hospital. PATIENTS: 360 patients were identified prospectively by referral to our center for management or surveillance of PCC/PGL. The median age was 59 years (IQR 45-67) and 56.4% (n = 203) were female. MAIN OUTCOME MEASURES: The primary and secondary outcomes were weight and HbA1c, respectively. RESULTS: On multivariable MEM, norepinephrine (P < 0.0005) negatively correlated with weight when all catecholamines and their derivatives were tried in the model, and normetanephrine (P < 0.0005) correlated when only metanephrines were included. In the surgical cohort (n = 272), normetanephrine decreased postoperatively and was inversely associated with weight (P < 0.0005). Elevated norepinephrine or normetanephrine at the study termination, indicative of metastatic and/or recurrent disease (MRD), correlated with weight loss. Norepinephrine and normetanephrine (P < 0.0005) directly correlated with HbA1c. CONCLUSION: Plasma norepinephrine and its metabolite directly correlate with HbA1c and inversely correlate with weight in PCC/PGL. After resection, declining normetanephrine levels correlate with improving HbA1c despite an increase in patient body weight. Persistently elevated catecholamines and decreasing weight are observed in MRD.

Prostate-Specific Antigen Concentrations in Response to Testosterone Treatment of Severely Hypogonadal Men.

CONTEXT: Clinical guidelines recommend measurement of the serum prostate-specific antigen (PSA) concentration during testosterone treatment of hypogonadal men to determine whether the increase is sufficiently high to warrant urologic referral. Prior studies of the effect of testosterone treatment on PSA concentrations have been conducted in men who were mildly to moderately hypogonadal. OBJECTIVE: The objective of this work is to determine the PSA response to testosterone treatment of men who are severely hypogonadal. DESIGN AND SETTING: This retrospective cohort study was conducted at a single academic medical center. PARTICIPANTS: Eighty-five men participated who were severely hypogonadal as a result hypothalamic-pituitary or testicular disease. MAIN OUTCOME MEASURE: Changes in serum PSA concentrations were measured during testosterone treatment for up to 18 months. RESULTS: Testosterone treatment increased the median serum testosterone concentration from 36 ng/dL (interquartile range [IQR], 20-91 ng/dL) at baseline to 395 ng/dL (IQR, 266-542 ng/dL) at 6 to 18 months. This treatment resulted in a median increment in PSA above baseline of 0.70 ng/mL (IQR, 0.10-1.85 ng/mL) at 6 to 18 months. Apropos current Endocrine Society clinical guidelines, 31% of the men experienced a PSA increase above baseline greater than 1.4 ng/mL, and 13% reached an absolute PSA concentration of greater than 4.0 ng/mL. Four men were diagnosed with prostate cancer. CONCLUSIONS: The PSA response to testosterone replacement in men who are severely hypogonadal as a result of pituitary or testicular disease is greater than that previously reported in men with mild to moderate hypogonadism. These results suggest the magnitude of the PSA response to testosterone replacement is related to the degree of hypogonadism.

Clinical Utility of Plasma Cell-Free DNA in Adult Patients with Newly Diagnosed Glioblastoma: A Pilot Prospective Study.

PURPOSE: The clinical utility of plasma cell-free DNA (cfDNA) has not been assessed prospectively in patients with glioblastoma (GBM). We aimed to determine the prognostic impact of plasma cfDNA in GBM, as well as its role as a surrogate of tumor burden and substrate for next-generation sequencing (NGS). EXPERIMENTAL DESIGN: We conducted a prospective cohort study of 42 patients with newly diagnosed GBM. Plasma cfDNA was quantified at baseline prior to initial tumor resection and longitudinally during chemoradiotherapy. Plasma cfDNA was assessed for its association with progression-free survival (PFS) and overall survival (OS), correlated with radiographic tumor burden, and subjected to a targeted NGS panel. RESULTS: Prior to initial surgery, GBM patients had higher plasma cfDNA concentration than age-matched healthy controls (mean 13.4 vs. 6.7 ng/mL, P < 0.001). Plasma cfDNA concentration was correlated with radiographic tumor burden on patients' first post-radiation magnetic resonance imaging scan (ρ = 0.77, P = 0.003) and tended to rise prior to or concurrently with radiographic tumor progression. Preoperative plasma cfDNA concentration above the mean (>13.4 ng/mL) was associated with inferior PFS (median 4.9 vs. 9.5 months, P = 0.038). Detection of ≥1 somatic mutation in plasma cfDNA occurred in 55% of patients and was associated with nonstatistically significant decreases in PFS (median 6.0 vs. 8.7 months, P = 0.093) and OS (median 5.5 vs. 9.2 months, P = 0.053). CONCLUSIONS: Plasma cfDNA may be an effective prognostic tool and surrogate of tumor burden in newly diagnosed GBM. Detection of somatic alterations in plasma is feasible when samples are obtained prior to initial surgical resection.

Concerns and Expectations of Parents Seeking Subspecialist Care for Their Child's Short Stature.

INTRODUCTION: Parents (PP) of children in primary care clinics previously reported factors influencing their height-related medical decision making. However, patients seeking height-related care in endocrine subspecialty clinics and their parents (EP) differ demographically from the general population. OBJECTIVE: To determine EP height-related medical concerns and expectations, and to compare between EP and PP. METHODS: EP completed a survey assessing their concerns in seeking medical care for their child's height with identical questions previously asked of PP and two additional questions about growth hormone (GH) treatment. RESULTS: A greater proportion of the 166 EP (80% response rate) than the 1,820 PP (83% response rate) previously surveyed was Caucasian (75% EP, 41% PP) and privately insured (80% EP, 58% PP). Both groups rated treatment efficacy and risks most as having a bigor extreme impact on decision making (65% EP, 58% PP). The second most rated concern for EP was comparison of child's height to peers or growth chart (60% EP, 32% PP) versus child's health for PP (54% EP, 56% PP). Of the 166 EP surveyed, 76% rated GH treatment as potentially improving quality of life (QoL), with 88% reporting a minimum 3-inch height increase as necessary to improve QoL. CONCLUSIONS: Height comparisons were more likely to impact EP than PP in seeking height-related medical care for their children. EP had high expectations of QoL improvement with GH treatment, which are unlikely to be met with treatment of idiopathic short stature. Thus, clinicians should be prepared to support families in other ways that promote positive development in children with short stature.

Racial/Ethnic Disparities in US Pediatric Growth Hormone Treatment.

BACKGROUND/AIMS: To compare racial/ethnic proportions of subjects receiving growth hormone (GH) treatment to the expected proportions, and secondarily, to assess racial/ethnic differences in subject characteristics at GH treatment initiation. METHODS: Race/ethnicity-based expected frequencies of height <-2.25 SD were determined by applying relative risks for short stature, calculated from a regional population of 189,280 pediatric primary care patients, to US census data, and compared to racial/ethnic proportions of US subjects enrolled in the Pfizer International Growth Study (KIGS) using the χ2 test. Characteristics of white and black subjects at GH treatment initiation were presented as medians and compared by the Wilcoxon rank sum test (significant p < 0.01). RESULTS: White subjects exceeded the expected frequency (63%) for all indications (83%) and each separately, ranging from 73% for congenital GH deficiency (GHD) to 85% for idiopathic short stature (p < 0.001). Compared to white subjects, black subjects treated for idiopathic GHD had greater height deficits relative both to the population (-2.97 vs. -2.56 SD) and to their mid-parental heights (-2.47 vs. -1.89 SD), lower stimulated GH peak levels (4.9 vs. 6.0 ng/mL), and lower birth weights (-0.86 vs. -0.48 SD). Black subjects with congenital GHD had lower stimulated GH peaks (2.1 vs. 3.2 ng/mL) and started GH treatment at younger ages (2.9 vs. 4.8 years), while those with acquired GHD had lower birth weights (-1.12 vs. -0.08 SD). Male predominance did not differ by race for any or all indications. CONCLUSION: Overrepresentation of white children among those receiving GH treatment in the US KIGS registry reflects racial/ethnic treatment biases, not just differences in growth rates.

A Breathing-Based Meditation Intervention for Patients With Major Depressive Disorder Following Inadequate Response to Antidepressants: A Randomized Pilot Study.

OBJECTIVE: To evaluate feasibility, efficacy, and tolerability of Sudarshan Kriya yoga (SKY) as an adjunctive intervention in patients with major depressive disorder (MDD) with inadequate response to antidepressant treatment. METHODS: Patients with MDD (defined by DSM-IV-TR) who were depressed despite ≥ 8 weeks of antidepressant treatment were randomized to SKY or a waitlist control (delayed yoga) arm for 8 weeks. The primary efficacy end point was change in 17-item Hamilton Depression Rating Scale (HDRS-17) total score from baseline to 2 months. The key secondary efficacy end points were change in Beck Depression Inventory (BDI) and Beck Anxiety Inventory (BAI) total scores. Analyses of the intent-to-treat (ITT) and completer sample were performed. The study was conducted at the University of Pennsylvania between October 2014 and December 2015. RESULTS: In the ITT sample (n = 25), the SKY arm (n = 13) showed a greater improvement in HDRS-17 total score compared to waitlist control (n = 12) (-9.77 vs 0.50, P = .0032). SKY also showed greater reduction in BDI total score versus waitlist control (-17.23 vs -1.75, P = .0101). Mean changes in BAI total score from baseline were significantly greater for SKY than waitlist (ITT mean difference: -5.19; 95% CI, -0.93 to -9.34; P = .0097; completer mean difference: -6.23; 95% CI, -1.39 to -11.07; P = .0005). No adverse events were reported. CONCLUSIONS: Results of this randomized, waitlist-controlled pilot study suggest the feasibility and promise of an adjunctive SKY-based intervention for patients with MDD who have not responded to antidepressants. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02616549.

Transplantation of Center for Disease Control "High-Risk" Donor Hearts Does Not Adversely Impact Long-Term Outcomes in Adults.

BACKGROUND: The "high-risk donor" (HRD) label was applied to donors who met the Centers for Disease Control and Prevention criteria for high-risk behavior in 2004. The number of potential recipients who die awaiting orthotopic heart transplantation (OHT) has increased. Despite organ shortages, HRD grafts are often declined given infectious concerns. We hypothesized that recipients would have equivalent outcomes. METHODS: We retrospectively analyzed the United Network of Organ Sharing adult heart transplant data from June 2004 to December 2013. OHT recipients were divided into 2 cohorts by donor status. RESULTS: During the study period, 37,408 OHTs were performed and 3196 (8.5%) patients received HRD grafts. Recipients of HRD were significantly older (P < .0001) and had a higher body mass index (P < .0001) compared with standard-risk donor recipients. No significant difference in waitlist time (P = .69) or blood type (P = .07) was noted. A higher number of HRD recipients were on mechanical circulatory support (35.6%) compared with standard-risk donor (33.3%, P = .009). Both grafts manifested similar, low rates of rejection before discharge (P = .88). One1 (84.3 vs 83%) and 5-year (71.2 vs 65.5%) survival was similar in the cohorts (log-rank P = .7571). CONCLUSIONS: HRD status does not significantly affect recipient outcomes after OHT. Increased use of HRD grafts could augment donor pool and decrease the mortality associated with long waitlist times.

Electronic Health Record Mid-Parental Height Auto-Calculator for Growth Assessment in Primary Care.

Primary care providers are charged with distinguishing children with an underlying growth problem from those with healthy variant short stature. Knowing the heights of the biological parents aids in making that decision. This study sought to determine the feasibility and functionality of an electronic mid-parental height (MPH) auto-calculator in the clinical assessment of child growth in a pediatric primary care setting. Clinicians completed surveys for 62% of 6803 children (mean height 13 ± 7 percentile) with recorded parent heights. Collecting parent height data required <30 seconds in 91% of encounters. The MPH tool confirmed clinicians' initial growth assessment in 79% of cases and changed it in 4%; the remainder did not use the tool. Clinicians who changed assessment were more likely (P < .0001) to pursue more comprehensive evaluation. The MPH tool was a quick, functional resource as a component of an electronic health record system in actual, busy, pediatric primary care practices.

Parental Concerns Influencing Decisions to Seek Medical Care for a Child's Short Stature.

AIMS: To examine parental concerns about child growth and factors that drive parents' decisions whether to intervene medically with their child's height. METHODS: Parents of 9- to 14-year-old pediatric primary care patients of various heights, oversampled for those with short stature, participated in exploratory focus groups and nominal group technique sessions. Growth concerns expressed by the groups were incorporated into a survey, completed by 1,820 parents, and rated for their degree of impact on medical decision-making. Ordinal logistic regression modeled concern scores against parent traits. Explanatory focus groups clarified the survey results. RESULTS: Research team consensus and factor analysis organized the 22 distinct concerns expressed by the parent groups into 7 categories. Categories rated as having the greatest influence on parental decision-making involved: treatment efficacy and side effects, child health and psychosocial function. Level of concern was highly associated with parental education and parenting style. CONCLUSION: Psychosocial issues are influential, but parental decision-making is most impacted by concerns about treatment and child health. By discussing the real risks and benefits of hormone treatment and addressing parents' perceptions of what is needed for physical and psychosocial health, clinicians can be highly effective educators to assure that treatment is used only as medically indicated.

Gender Bias in U.S. Pediatric Growth Hormone Treatment.

Growth hormone (GH) treatment of idiopathic short stature (ISS), defined as height <-2.25 standard deviations (SD), is approved by U.S. FDA. This study determined the gender-specific prevalence of height <-2.25 SD in a pediatric primary care population, and compared it to demographics of U.S. pediatric GH recipients. Data were extracted from health records of all patients age 0.5-20 years with ≥ 1 recorded height measurement in 28 regional primary care practices and from the four U.S. GH registries. Height <-2.25 SD was modeled by multivariable logistic regression against gender and other characteristics. Of the 189,280 subjects, 2073 (1.1%) had height <-2.25 SD. No gender differences in prevalence of height <-2.25 SD or distribution of height Z-scores were found. In contrast, males comprised 74% of GH recipients for ISS and 66% for all indications. Short stature was associated (P < 0.0001) with history of prematurity, race/ethnicity, age and Medicaid insurance, and inversely related (P < 0.0001) with BMI Z-score. In conclusion, males outnumbered females almost 3:1 for ISS and 2:1 for all indications in U.S. pediatric GH registries despite no gender difference in height <-2.25 SD in a large primary care population. Treatment and/or referral bias was the likely cause of male predominance among GH recipients.

Hemiparesis and epilepsy are associated with worse reported health status following unilateral stroke in children.

BACKGROUND: Perinatal and childhood stroke result in neurological impairment in the majority of survivors, but less is known about patient and parent perception of function following stroke in children. Our aim was to characterize parent-proxy and child-reported health status in children following unilateral arterial ischemic stroke or intraparenchymal hemorrhage. METHODS: Fifty-nine children 2-18 years (30 girls, 29 boys) with unilateral arterial ischemic stroke or spontaneous intraparenchymal hemorrhage at least 6 months before evaluation were enrolled from a single center. The PedsQL version 4.0 Generic Short Form and PedsQL version 3.0 Cerebral Palsy Module were administered to childhood stroke subjects and parents. Generic PedsQL Inventory scores were compared between children with stroke and published data from healthy children. Reported health status scores for children with varying degrees of hemiparesis were compared. RESULTS: Children with stroke had lower reported health status scores on the Generic PedsQL Inventory than healthy children. Children with moderate-severe hemiparesis had worse scores than children without hemiparesis on several measures of the Cerebral Palsy Module as reported by both parents and children. The parents of children with epilepsy reported worse scores on several measures compared with children without epilepsy, and the parent scores were lower on several measures for children with lower intelligence quotients. Agreement between parent and child scores was better on the Cerebral Palsy Module than on the Generic Inventory. CONCLUSIONS: Children with stroke have worse reported health status than healthy controls. Degree of hemiparesis, epilepsy, and lower intelligence quotient affect reported health status on some measures. Agreement between parent-proxy and child scores ranges from slight to good which suggests that both provide useful information.

Assessing statistical competencies in clinical and translational science education: one size does not fit all.

INTRODUCTION: Statistics is an essential training component for a career in clinical and translational science (CTS). Given the increasing complexity of statistics, learners may have difficulty selecting appropriate courses. Our question was: what depth of statistical knowledge do different CTS learners require? METHODS: For three types of CTS learners (principal investigator, co-investigator, informed reader of the literature), each with different backgrounds in research (no previous research experience, reader of the research literature, previous research experience), 18 experts in biostatistics, epidemiology, and research design proposed levels for 21 statistical competencies. RESULTS: Statistical competencies were categorized as fundamental, intermediate, or specialized. CTS learners who intend to become independent principal investigators require more specialized training, while those intending to become informed consumers of the medical literature require more fundamental education. For most competencies, less training was proposed for those with more research background. DISCUSSION: When selecting statistical coursework, the learner's research background and career goal should guide the decision. Some statistical competencies are considered to be more important than others. Baseline knowledge assessments may help learners identify appropriate coursework. CONCLUSION: Rather than one size fits all, tailoring education to baseline knowledge, learner background, and future goals increases learning potential while minimizing classroom time.

How Short is Too Short According to Parents of Primary Care Patients.

OBJECTIVE: Height is a physical trait on a continuum. The threshold between normal and abnormal is arbitrarily set but can potentially influence medical decision-making. We sought to examine parents' perceptions of adult heights and associated demographic factors. METHODS: Parents of pediatric primary care patients of various heights completed a one-time survey. Parents answered the question "How short is too short?" for adult males and females. The results were summarized as median [interquartile range]. Factors significantly associated with height threshold by simple linear regression were included in a multivariable mixed effects analysis of covariance model. RESULTS: A total of 1,820 surveys were completed (83% response rate; 1,587 females, 231 males). The median threshold height deemed too short for adult females was 56 inches [48, 59] among male respondents and 57 inches [50, 60] among females (P<.05). The median threshold height for adult males was 61 inches among males [60, 64] and females [59, 66] (P<.05). The median of male minus female heights per respondent (delta heights) was 5 [2, 7] inches. Factors found to be significant main effects in a parsimonious model were sex of the adult considered, height of respondent, sex of respondent, respondent race, primary care practice, income, and having concerns about their child's height. CONCLUSION: Taller acceptable height thresholds were perceived by respondents who were taller, wealthier, white, female, from nonurban practices, or who had a personal concern about their child's height. Male heights were expected to be taller than female heights. Such traits may influence who is concerned and more likely to seek medical treatment for their children.

Blood pressure variability of two ambulatory blood pressure monitors.

OBJECTIVE: There are no data on the evaluation of blood pressure (BP) variability comparing two ambulatory blood pressure monitoring monitors worn at the same time. Hence, this study was carried out to compare variability of BP in healthy untreated adults using two ambulatory BP monitors worn at the same time over an 8-h period. METHODS: An Accutorr device was used to measure office BP in the dominant and nondominant arms of 24 participants.Simultaneous 8-h BP and heart rate data were measured in 24 untreated adult volunteers by Mobil-O-Graph (worn for an additional 16 h after removing the Spacelabs monitor) and Spacelabs with both random (N=12) and nonrandom (N=12) assignment of each device to the dominant arm. Average real variability (ARV), SD, coefficient of variation, and variation independent of mean were calculated for systolic blood pressure, diastolic blood pressure, mean arterial pressure, and pulse pressure (PP). RESULTS: Whether the Mobil-O-Graph was applied to the dominant or the nondominant arm, the ARV of mean systolic (P=0.003 nonrandomized; P=0.010 randomized) and PP (P=0.009 nonrandomized; P=0.005 randomized) remained significantly higher than the Spacelabs device, whereas the ARV of the mean arterial pressure was not significantly different. The average BP readings and ARVs for systolic blood pressure and PP obtained by the Mobil-O-Graph were considerably higher for the daytime than the night-time. CONCLUSION: Given the emerging interest in the effect of BP variability on health outcomes, the accuracy of its measurement is important. Our study raises concerns about the accuracy of pooling international ambulatory blood pressure monitoring variability data using different devices.

Intravenous GLP-1 (7-36) amide for prevention of hyperglycemia during cardiac surgery: a randomized, double-blind, placebo-controlled study.

OBJECTIVE: The authors sought to evaluate the efficacy of an intravenous glucagon-like peptide-1 (GLP-1) infusion, compared with placebo, to mitigate intraoperative hyperglycemia. DESIGN: Prospective, double-blinded, randomized, placebo-controlled. SETTING: University hospital. PARTICIPANTS: Diabetic (non-insulin dependent) and non-diabetic patients undergoing elective cardiac surgery with cardiopulmonary bypass. INTERVENTIONS: Patients were randomized in a 1:1 fashion to GLP-1 (7-36) amide infusion (1.5 pmol/kg/min) or placebo. Insulin was administered intraoperatively to both groups per a standardized protocol. MEASUREMENTS AND MAIN RESULTS: A total of 77 patients were included for analysis (GLP-1, n = 37; placebo, n = 40). Mean blood glucose during cardiopulmonary bypass was 127.5 mg/dL and 142.5 mg/dL (p = 0.002) in the GLP-1 and placebo groups, respectively. Mean blood glucose values during the entire intraoperative course were 12.2 mg/dL lower for subjects given GLP-1 (95% CI 2.3, 22, p = 0.015), independent of time. During the period of cardiopulmonary bypass, mean blood glucose values in subjects given GLP-1 were 14.1 mg/dL lower than those who received placebo (95% CI 3.5, 24.8, p = 0.009), independent of time. The incidence of hypoglycemia did not differ significantly between the 2 groups. CONCLUSIONS: Administration of intravenous GLP-1 (7-36) amide to patients undergoing cardiac surgery significantly reduced their plasma glucose levels intraoperatively and may represent a novel therapeutic strategy to prevent perioperative hyperglycemia.

Medically underserved girls receive less evaluation for short stature.

OBJECTIVE: To determine if gender is associated with diagnostic evaluation by primary care pediatricians caring for children with growth-faltering. PATIENTS AND METHODS: This was a retrospective study of children who were attending 4 urban pediatric primary care practices affiliated with a tertiary pediatric hospital. Growth-faltering was defined as height at the <5th percentile or a z-score decrease of ≥ 1.5 SDs before 18 months of age or ≥ 1 SD thereafter. For each child, height z score, age, gender, race, insurance, diagnostic tests, and subspecialist appointments were examined. RESULTS: Of 33 476 children, 3007 had growth-faltering (mean height: -1.5 ± 1.0 vs 0.3 ± 0.9 SDs in those without growth-faltering). Boys comprised 53% of the growth-faltering group (vs 51% of the nonfaltering group; P < .01). Among children with growth-faltering, 2.8% had endocrinology appointments (vs 0.8% of others; P < .0001) and 6% had gastroenterology appointments (vs 1.5% of others; P < .0001). Subspecialty care was not associated with gender. Pediatricians ordered diagnostic tests for a significantly greater proportion of children with growth-faltering than others. In multivariate analysis of height z score among children with growth-faltering, tests for chromosomes (1.4% of short girls vs 0.4% of short boys; P < .005) and growth hormone/insulin-like growth factor axis (0.9% of short girls vs 1.8% of short boys; P < .05) were associated with gender. Thirty-five percent of the girls for whom chromosome testing was performed were 12 years old or older. CONCLUSIONS: Patterns in diagnostic testing of children with growth-faltering by their pediatricians may lead to underdiagnosis of Turner syndrome and growth hormone deficiency among girls.

Hemorrhagic transformation of childhood arterial ischemic stroke.

BACKGROUND AND PURPOSE: The objective of this study was to describe the occurrence of hemorrhagic transformation (HT) among children with arterial ischemic stroke within 30 days after symptom onset and to describe clinical factors associated with HT. METHODS: Sixty-three children aged 1 month to 18 years with arterial ischemic stroke between January 2005 and November 2008 were identified from a single-center prospective pediatric stroke registry. All neuroimaging studies within 30 days of stroke were reviewed by a study neuroradiologist. Hemorrhage was classified according to the European Cooperative Acute Stroke Study-1 definitions. Association of HT with clinical factors, systemic anticoagulation, stroke volume, and outcome was analyzed. RESULTS: HT occurred in 19 of 63 children (30%; 95% CI, 19% to 43%), only 2 (3%) of whom were symptomatic. Hemorrhage classification was hemorrhagic infarction (HI)1 in 14, HI2 in 2, parenchymal hematoma (PH)1 in 2, and PH2 in 1. HT was less common in children with vasculopathy (relative risk, 0.27; 95% CI, 0.07 to 1.06; P=0.04) than in those with other stroke mechanisms. HT was not significantly associated with anticoagulation versus antiplatelet therapy (relative risk, 0.6; 95% CI, 0.2 to 1.5; P=0.26) but was associated with larger infarct volumes (P=0.0084). In multivariable analysis, worse Pediatric Stroke Outcome Measure scores were associated with infarct volume ≥5% of total supratentorial brain volume (OR, 4.0; 95% CI, 1.1 to 15; P=0.04), and a trend existed toward association of worse Pediatric Stroke Outcome Measure scores with HT (OR, 4.0; 95% CI, 0.9 to 18; P=0.07). CONCLUSIONS: HT occurred in 30% of children with arterial ischemic stroke within 30 days. Most hemorrhages were petechial and asymptomatic. Infarct volume was associated with HT and worse outcome.

The effect of age, menopausal state, and breast density on (18)F-FDG uptake in normal glandular breast tissue.

UNLABELLED: Theoretically, the degree of (18)F-FDG uptake in the glandular tissues of the normal breast can affect the detection of breast cancer. The aim of this prospective study was to investigate relationships among age, menopausal state, and breast density and determine whether they affect (18)F-FDG uptake in normal glandular breast tissue. METHODS: Among 250 newly diagnosed breast cancer patients, 149 patients (mean age +/- SD, 50.9 +/- 9.70 y; range, 32-77 y) were analyzed because they had normal contralateral breasts confirmed by MRI, mammography, and (18)F-FDG PET examinations. PET images were acquired 60 +/- 2 min after the administration of (18)F-FDG (5.2 MBq/kg of body weight). The maximum and average standardized uptake value (SUVmax and SUVavg, respectively) of (18)F-FDG were calculated in the normal breast. Patients were divided into groups according to qualitative breast density and menopausal state. Descriptive statistics and 2-factorial analysis of covariance were used to assess the effects of qualitative breast density, menopausal state, and age on SUVmax and SUVavg. Pearson chi(2) was used to test the relationship between menopausal state and qualitative breast density. RESULTS: The average age of patients with nondense breasts was significantly higher than that of patients with dense breasts (P < 0.01). Also, breast density related to menopausal state (P < 0.05). Dense breasts had an average SUVmax of 1.243 and mean SUVavg of 0.694, whereas nondense breasts had a mean SUVmax of 0.997 and mean SUVavg of 0.592. Analysis of covariance indicated that density and the linear effect of age were significant with regard to both SUVmax and SUVavg. After removing the linear effect of age, menopausal state had no effect on SUVmax and SUVavg. CONCLUSION: (18)F-FDG uptake significantly decreases as age increases and breast density decreases. Age and qualitative breast density are independent factors and significantly affect (18)F-FDG uptake for both SUVmax and SUVavg. Menopausal state had no effect on SUVmax and SUVavg.

Sex-based prevalence of growth faltering in an urban pediatric population.

OBJECTIVE: To determine the sex-based prevalence of growth faltering in a pediatric primary care setting. STUDY DESIGN: A total of 33 476 children attending 4 urban pediatric primary care practices affiliated with a tertiary pediatric hospital between July 2002 and June 2005 were studied. Growth faltering was defined as height <5th percentile or a drop in height z-score by >or= 1.5 standard deviations (SD) before age 18 months or by >or= 1 SD thereafter. The growth-faltering and nonfaltering groups were compared in terms of sex, race, age, number of clinic visits, and insurance, and by US census tract, socioeconomic status and parental education. Similar comparisons were made for children with height z-scores below -2.25 SD. RESULTS: Growth faltering was present in 3007 of the children studied (9%). Univariate and multivariate logistic regression analyses identified significant associations between growth faltering and younger age (P< .0001), Caucasian race (P< .0001), fewer clinic visits (P< .0001), and Medicaid insurance (P< .005), but not with sex nor by residential census tract, median income or proportion with less than high school education. Height below -2.25 SD was associated with male sex (P< .01), Medicaid insurance (P< .01), and more primary care visits (P< .0005). CONCLUSIONS: The sex disparity in subspecialty growth center referrals (2:1 male:female) is not due to male predominance in growth faltering among children in the urban primary care setting.

Functional polymorphisms of folate-metabolizing enzymes in relation to homocysteine concentrations in systemic lupus erythematosus.

OBJECTIVE: To determine if functional polymorphisms of folate/homocysteine pathway enzymes are associated with homocysteine concentrations and/or coronary artery calcification (CAC) scores in patients with systemic lupus erythematosus (SLE) and controls. METHODS: We investigated 163 SLE patients and 160 controls. Functional polymorphisms in 6 genes in the folate/homocysteine pathway were genotyped: 5,10-methylenetetrahydrofolate reductase (MTHFR) 677C>T, MTHFR 1298A>C, cystathionine ss-synthase (CBS) 844ins68, methionine synthase (MTR) 2756A>G, methionine synthase reductase (MTRR) 66A>G, thymidylate synthase (TYMS) 1494del6, and dihydrofolate reductase (DHFR) c.86+60_78. RESULTS: Homocysteine levels were higher in African American SLE patients than Caucasian patients and African American controls. Genotype distributions were significantly different in African American and Caucasian controls for 6 of the 7 polymorphisms. Genotype distributions for each polymorphism did not differ significantly between SLE patients and controls even after stratification by race. Glomerular filtration rate was strongly negatively correlated to homocysteine levels, and was therefore adjusted for as a covariate in the models of the effects of the polymorphisms on homocysteine levels. In SLE patients none of the 7 polymorphisms was associated with homocysteine concentrations. In Caucasian controls only MTHFR 677C>T and 1298A>C showed effects on homocysteine similar to what would be expected from the literature. There were no genotypic associations with median CAC scores in SLE patients or controls with and without stratification by race. CONCLUSION: Polymorphisms in folate/homocysteine metabolizing enzymes do not predict higher homocysteine levels or CAC scores in patients with SLE.