Circulating CTRP9 Is Associated With Severity of Systemic Sclerosis-Associated Interstitial Lung Disease.

OBJECTIVE: While interstitial lung disease (ILD) is the leading cause of morbidity and mortality in systemic sclerosis (SSc), there remains a paucity of predictive markers to assess disease progression. We previously demonstrated that adipose tissue metabolism and adipokine homeostasis is dysregulated in SSc. The present study was undertaken to determine the association and predictive ability of the novel adipokine C1q/tumor necrosis factor-related protein 9 (CTRP9) for SSc-associated ILD. METHODS: We performed a retrospective longitudinal study utilizing the Northwestern Scleroderma Program Patient Registry and Biorepository. Serum levels of CTRP9 were measured in 110 SSc patients at baseline, and demographic, clinical, and pulmonary function test data were collected in 12-month intervals to 48 months. Longitudinal trajectory of forced vital capacity percent predicted (FVC%) was used as a primary outcome measure. We utilized a mixed model to compare trajectories of lung function by CTRP9 groups and performed latent trajectory analysis to accommodate for heterogeneity. RESULTS: In cross-sectional analysis, elevated circulating CTRP9 was associated with significantly lower FVC% at baseline (72% ± 17 versus 80% ± 18; P = 0.02) and 48 months (68 ± 19 versus 84 ± 18; P = 0.001). In mixed model analysis, high CTRP9 was associated with worse lung function but not with a different trajectory (P = 0.23). In contrast, low CTRP9 identified patients with stability of lung disease with reasonable accuracy (sensitivity 73%). Latent trajectory analysis confirmed the association of lower CTRP9 with higher FVC%. CONCLUSION: Higher circulating CTRP9 associated with worse pulmonary function, while low CTRP9 identified patients with lung disease stability over time. These findings suggest that CTRP9 may be a potential biomarker in SSc-associated ILD.

Disparities in first evaluation of infants with cystic fibrosis since implementation of newborn screening.

OBJECTIVE: We evaluated whether implementation of cystic fibrosis (CF) newborn screening (NBS) leads to equitable timeliness of initial evaluation. We compared age at first event (AFE, age at sweat test, encounter and/or care episode) between infants categorized as Black/African American, American Indian/ Native Alaskan, Asian, and/or Hispanic and/or other (Group 1) to White and not Hispanic infants (Group 2). METHODS: This retrospective cohort study from the Cystic Fibrosis Foundation Patient Registry (CFFPR) included infants born 2010-2018. Race and ethnicity categories followed US Census definitions. The primary outcome was AFE; the secondary outcome was weight for age (WFA) z-score averaged 12 to < 24 months. We compared distributions by Wilcoxon rank-sum test and proportions by Chi-square or Fisher's exact tests. A nested cohort study used a linear mixed effects model of variables that affect WFA, chosen a priori, to evaluate associations with 1-year WFA z-score. RESULTS: Among 6354 infants, 21% were in Group 1. Group 1 median AFE was 31 days (IQR 19, 49) and Group 2 was 22 days (IQR 14,36) (p< .001). Median WFA z-score at 1-2 years was lower in Group 1. In 3017 infants with complete data on variables of interest, AFE, Black race, CFTR variant class I-III, prematurity and public insurance were associated with lower 1-year WFA z-score. CONCLUSIONS: Differences in AFE for infants with CF from historically marginalized groups may exacerbate long standing health disparities. We speculate that inequitable identification of CFTR gene variants and/or bias may influence timeliness of evaluation after an out-of-range NBS.

Clinical evaluation of the Diagnostic Analyzer for Selective Hybridization (DASH): A point-of-care PCR test for rapid detection of SARS-CoV-2 infection.

BACKGROUND: An ideal test for COVID-19 would combine the sensitivity of laboratory-based PCR with the speed and ease of use of point-of-care (POC) or home-based rapid antigen testing. We evaluated clinical performance of the Diagnostic Analyzer for Selective Hybridization (DASH) SARS-CoV-2 POC rapid PCR test. METHODS: We conducted a cross-sectional study of adults with and without symptoms of COVID-19 at four clinical sites where we collected two bilateral anterior nasal swabs and information on COVID-19 symptoms, vaccination, and exposure. One swab was tested with the DASH SARS-CoV-2 POC PCR and the second in a central laboratory using Cepheid Xpert Xpress SARS-CoV-2 PCR. We assessed test concordance and calculated sensitivity, specificity, negative and positive predictive values using Xpert as the "gold standard". RESULTS: We enrolled 315 and analyzed 313 participants with median age 42 years; 65% were female, 62% symptomatic, 75% had received ≥2 doses of mRNA COVID-19 vaccine, and 16% currently SARS-CoV-2 positive. There were concordant results for 307 tests indicating an overall agreement for DASH of 0.98 [95% CI 0.96, 0.99] compared to Xpert. DASH performed at 0.96 [95% CI 0.86, 1.00] sensitivity and 0.98 [95% CI 0.96, 1.00] specificity, with a positive predictive value of 0.85 [95% CI 0.73, 0.96] and negative predictive value of 0.996 [95% CI 0.99, 1.00]. The six discordant tests between DASH and Xpert all had high Ct values (>30) on the respective positive assay. DASH and Xpert Ct values were highly correlated (R = 0.89 [95% CI 0.81, 0.94]). CONCLUSIONS: DASH POC SARS-CoV-2 PCR was accurate, easy to use, and provided fast results (approximately 15 minutes) in real-life clinical settings with an overall performance similar to an EUA-approved laboratory-based PCR.

Real world use of peanut component testing among children in the Chicago metropolitan area.

Background: Peanut component tests (PCT) have become important in the evaluation of peanut allergy. There remains a paucity of research across the United States in investigating the utility of PCT in clinical practice in conjunction with current standards of care. Objective: The primary aims were to evaluate the performance and sensitization patterns of PCT in clinical practice when first available at our institution. Methods: We performed a retrospective chart review of 184 children with PCT and oral food challenge (OFC) results between 2012 and 2017. Simple logistic regression models assessed the associations between PCT and OFC outcomes. Receiver operator characteristic curves were constructed, and a predicted probability curve was derived for Ara h2. Results: The median (interquartile range [IQR]) age at OFC was 4 years (2-7 years), and 111 patients (60%) were boys. Ara h 2 was the most commonly sensitized PCT. Sixty-one patients (33%) reacted at OFC. Ara h 2 specific immunoglobulin E (sIgE) ≥ 0.35 kUA/L was associated with increased odds of reacting at OFC (odds ratio 5.91 95% confidence interval, 2.93-11.89; p < 0.001); however, 19 patients (37%) positive for Ara h 2 did not react. Ara h 2 sIgE of 0.49 kUA/L and 4.58 kUA/L were associated with 50% and 90% probability, respectively, of reacting at OFC. Among those sensitized only to Ara h 8 or 9 (n = 21), 86% had no reaction. There was no statistically significant association with polysensitization to Ara h 1, 2, and 3, and peanut OFC outcome. Conclusion: Although the Ara h 2 sIgE value was associated with clinical reactivity, a significant proportion of the patients sensitized to Ara h 2 tolerated peanut. OFC remains an important tool in the evaluation of peanut allergy.

Postoperative but not preoperative depression is associated with cognitive impairment after cardiac surgery: exploratory analysis of data from a randomized trial.

BACKGROUND: In this study we hypothesize that depression is associated with perioperative neurocognitive dysfunction and altered quality of life one month after surgery. METHODS: Data were obtained as part of a study evaluating cerebral autoregulation monitoring for targeting arterial pressure during cardiopulmonary bypass. Neuropsychological testing was performed before surgery and one month postoperatively. Testing included the Beck Depression Inventory, a depression symptoms questionnaire (0-63 scale), as well as anxiety and quality of life assessments. Depression was defined as a Beck Depression Inventory score > 13. RESULTS: Beck Depression data were available from 320 patients of whom cognitive domain endpoints were available from 88-98% at baseline and 69-79% after surgery. This range in end-points data was due to variability in the availability of each neuropsychological test results between patients. Depression was present in 50 (15.6%) patients before surgery and in 43 (13.4%) after surgery. Baseline depression was not associated with postoperative domain-specific neurocognitive function compared with non-depressed patients. Those with depression one month after surgery, though, had poorer performance on tests of attention (p = 0.017), memory (p = 0.049), verbal fluency (p = 0.010), processing speed (p = 0.017), and fine motor speed (p = 0.014). Postoperative neurocognitive dysfunction as a composite outcome occurred in 33.3% versus 14.5% of patients with and without postoperative depression (p = 0.040). Baseline depression was associated with higher anxiety and lower self-ratings on several quality of life domains, these measures were generally more adversely affected by depression one month after surgery. CONCLUSIONS: The results of this exploratory analysis suggests that preoperative depression is not associated with perioperative neurocognitive dysfunction, but depression after cardiac surgery may be associated with impairment in in several cognitive domains, a higher frequency of the composite neurocognitive outcome, and altered quality of life. TRIAL REGISTRATION: www. CLINICALTRIALS: gov, NCT00981474 (parent study).

Randomized trial of prophylactic antibiotics vs. placebo after midshaft-to-distal hypospadias repair: the PROPHY Study.

BACKGROUND: Use of prophylactic antibiotics after stented hypospadias repair is very common, but most research has not identified any clinical benefits of this practice. Only one study has found that postoperative prophylaxis reduces symptomatic urinary tract infections (UTIs). Data from the same trial suggested that prophylaxis may also reduce urethroplasty complications. No studies on this subject have been placebo-controlled. OBJECTIVE: We performed a randomized, double-blind, placebo-controlled study to evaluate the effect of postoperative prophylactic antibiotics on the incidence of infection or urethroplasty complications after stented repair of midshaft-to-distal hypospadias. STUDY DESIGN: Boys were eligible for this multicenter trial if they had a primary, single-stage repair of mid-to-distal hypospadias with placement of an open-drainage urethral stent for an intended duration of 5-10 days. Participants were randomized in a double-blind fashion to receive oral trimethoprim-sulfamethoxazole or placebo twice daily for 10 days postoperatively. The primary outcome was a composite of symptomatic UTI, surgical site infection (SSI), and urethroplasty complications, including urethrocutaneous fistula, meatal stenosis, and dehiscence. Secondary outcomes included each component of the primary outcome as well as acute adverse drug reactions (ADRs) and C. difficile colitis. RESULTS: Infection or urethroplasty complications occurred in 10 of 45 boys (22%) assigned to receive antibiotic prophylaxis as compared with 5 of 48 (10%) who received placebo (relative risk [RR], 2.1; 95% confidence interval [CI], 0.8 to 5.8; p = 0.16). There were no significant differences between groups in symptomatic UTIs, SSIs, or any urethroplasty complications. Mild ADRs occurred in 3 of 45 boys (7%) assigned to antibiotics as compared with 5 of 48 (10%) given placebo (RR, 0.6; 95% CI, 0.2 to 2.5; p = 0.72). There were no moderate-to-severe ADRs, and no patients developed C. difficile colitis. CONCLUSIONS: In this placebo-controlled trial of 93 patients, prophylactic antibiotics were not found to reduce infection or urethroplasty complications after stented mid-to-distal hypospadias repair. The study did not reach its desired sample size and was therefore underpowered to independently support a conclusion that prophylaxis is not beneficial. However, the result is consistent with most prior research on this subject. GOV IDENTIFIER: NCT02096159.

Clinical evaluation of the Diagnostic Analyzer for Selective Hybridization (DASH): a point-of-care PCR test for rapid detection of SARS-CoV-2 infection.

BACKGROUND: Rapid and accurate testing for SARS-CoV-2 is an essential tool in the medical and public health response to the COVID-19 pandemic. An ideal test for COVID-19 would combine the sensitivity of laboratory-based PCR combined with the speed and ease of use of point-of-care (POC) or home-based rapid antigen testing. METHODS: To evaluate the performance of the Diagnostic Analyzer for Selective Hybridization (DASH) SARS-CoV-2 POC PCR (sample insertion to result time of 16 minutes), we conducted a cross-sectional study of adults with and without symptoms of COVID-19 at four clinical sites. We collected two bilateral anterior nasal swabs from each participant and information on COVID-19 symptoms, vaccination, and exposure. One swab was tested with the DASH SARS-CoV-2 POC PCR and the second in a central laboratory using Cepheid Xpert Xpress SARS-CoV-2 PCR. We assessed test concordance and calculated sensitivity, specificity, negative and positive predictive values using Xpert as the "gold standard." RESULTS: We enrolled 315 and analyzed 313 participants with median age 42 years; 65% were female, 62% symptomatic, 75% had received ≥2 doses of mRNA COVID-19 vaccine, and 16% currently COVID-19 positive. There were concordant results for 307 tests indicating an overall agreement for DASH of 0.98 [95% CI 0.96, 0.99] compared to Xpert. DASH performed at 0.96 [95% CI 0.86, 1.00] sensitivity and 0.98 [95% CI 0.96, 1.00] specificity, with a positive predictive value of 0.85 [95% CI 0.73, 0.96] and negative predictive value of 0.996 [95% CI 0.99, 1.00]. The six discordant tests between DASH and Xpert all had high Ct values (>30) on the respective positive assay. DASH and Xpert Ct values were highly correlated (R=0.89 [95% CI 0.81, 0.94]). CONCLUSIONS: DASH POC SARS-CoV-2 PCR was accurate, easy to use, and provided fast results in real-life clinical settings with an overall performance similar to an EUA-approved laboratory-based PCR. Its compact design and ease of use are optimal for a variety of healthcare, and potentially community settings, including areas with lack of access to central laboratory-based PCR testing. SUMMARY: DASH is an accurate, easy to use, and fast point-of-care test with applications for diagnosis and screening of SARS-CoV-2 infection.

Distinct cord blood C-peptide, adipokine, and lipidomic signatures by in utero HIV exposure.

BACKGROUND: Early-life metabolic derangements in HIV-exposed uninfected (HEU) infants have been reported. METHODS: Pregnant women with HIV and HIV-uninfected pregnant women were enrolled with their newborns in a US cohort from 2011 to 2015. We measured cord insulin, C-peptide, and metabolic cytokines of HEU and HIV-unexposed uninfected (HUU) newborns using ELISA and metabolites, lipid subspecies, and eicosanoids via liquid chromatography/mass spectrometry. Linear regression was employed to assess the association of intrauterine HIV/ART with insulin and C-peptide. Graphical lasso regression was used to identify differences between metabolite/lipid subspecies networks associated with C-peptide. RESULTS: Of 118 infants, 56 were HEU, ART exposed. In adjusted analyses, mean cord insulin (ß = 0.295, p = 0.03) and C-peptide (ß = 0.522, p < 0.01) were significantly higher in HEU vs. HUU newborns. HEU neonates exhibited primarily positive associations between complex lipids and C-peptide, indicative of fuel storage, and augmented associations between cord eicosanoids and cytokines. HUU neonates exhibited negative associations with lipids and C-peptide indicative of increased fuel utilization. CONCLUSION: Higher cord insulin and C-peptide in HEU vs. HUU newborns as well as differences in cord metabolites, metabolic-related cytokines, and eicosanoids may reflect a propensity for fuel storage and an inflammatory milieu suggestive of fetal metabolic changes associated with in utero HIV/ART exposure. IMPACT: There is a paucity of studies assessing cord blood and neonatal metabolic health in HIV-exposed uninfected (HEU) newborns, an increasing population worldwide. Compared to HIV-unexposed uninfected (HUU) newborns, HEU newborns exhibit alterations in fuel homeostasis and an inflammatory milieu associated with in utero HIV/antiretroviral therapy (ART) exposure. The long-term implications of these neonatal findings are as yet unknown, but merit continued evaluation as this important and growing population ages into adulthood.

Early Growth and Cognitive Development in Children Born Preterm: Relevance of Maternal Body Mass Index.

OBJECTIVE: Maternal prepregnancy body mass index (BMI) represents a surrogate marker of fetal exposures to the maternal metabolism during pregnancy. Yet, it remains poorly understood whether this marker indicates risk of altered trajectories in postnatal growth and development in children born preterm. This study aimed to determine whether maternal prepregnancy BMI is associated with altered growth and development in children born preterm. STUDY DESIGN: A retrospective cohort study evaluated prepregnancy BMI as the exposure for childhood outcomes using linear regression and mixed effects models. The 38 children included in this follow-up evaluation originally participated in a prospective, observational cohort study to determine longitudinal levels of lipid species in preterm human milk expressed by women who delivered prior to 32 weeks. Childhood outcomes in this study were anthropometric measures during hospitalization (n = 38), after discharge through 36 months (n = 34) and Bayley-III developmental scores through 18 months corrected age (n = 26). RESULTS: In 38 children born prior to 32 weeks, higher maternal prepregnancy BMI was independently associated with higher preterm infant growth velocity during hospitalization, but not associated with in-hospital change in length or head circumference and/or postdischarge growth. In univariate linear regression models, higher maternal BMI was associated with lower cognitive scores at 18 months corrected age. This significant association remained in an adjusted model accounting for relevant influences on early childhood development. CONCLUSION: Increasing maternal prepregnancy BMI may reflect risk of altered growth and cognitive development in children born preterm. KEY POINTS: · Maternal BMI was associated with early preterm infant weight gain.. · Maternal BMI was not associated with postdischarge growth.. · Increased maternal BMI may be associated with lower cognitive function scores in offspring..

Preoperative Anemia and Risk for Perioperative Neurocognitive Dysfunction in Cardiac Surgery Patients: A Retrospective Analysis.

OBJECTIVES: To evaluate whether there is a relationship between preoperative anemia and domain-specific cognitive performance in patients undergoing cardiac surgery. DESIGN: Retrospective analysis of data collected from a randomized study. SETTING: Tertiary care university hospital. PARTICIPANTS: A total of 436 patients age ≥55 years undergoing cardiac surgery. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: Neuropsychological testing was performed before and one month after surgery, using a standard battery. Individual Z-scores calculated from the mean and standard deviation of tests at baseline were combined into domain-specific scores. Anemia (hemoglobin <130 g/L for men, <120 g/L for women) was present in 41% of patients. Preoperative anemia had little impact on preoperative cognition. There were no differences in the change in cognitive performance one month after surgery from baseline between patients with and without preoperative anemia. However, in a sensitivity analysis using multiple imputation for missing cognitive test scores, significant associations were observed between preoperative anemia and change in postoperative processing speed (p = 0.016), change in executive function (p = 0.049), and change in fine motor speed (p = 0.016). Nadir hemoglobin during cardiopulmonary bypass, which was lower in anemic than nonanemic patients, was associated with decrements in performance on tests of verbal fluency (p = 0.007), processing speed (p = 0.042), and executive function (p = 0.10) one month after surgery but not delayed neurocognitive recovery (p = 0.06). CONCLUSIONS: Preoperative anemia may be associated with impairment of selective cognitive domains after surgery. Any effect of preoperative anemia may have on cognition after surgery might be related to lower nadir hemoglobin during cardiopulmonary bypass.

Distinct Lipidomic Signatures in People Living With HIV: Combined Analysis of ACTG 5260s and MACS/WIHS.

CONTEXT: Disentangling contributions of HIV from antiretroviral therapy (ART) and understanding the effects of different ART on metabolic complications in persons living with HIV (PLHIV) has been challenging. OBJECTIVE: We assessed the effect of untreated HIV infection as well as different antiretroviral therapy (ART) on the metabolome/lipidome. METHODS: Widely targeted plasma metabolomic and lipidomic profiling was performed on HIV-seronegative individuals and people living with HIV (PLHIV) before and after initiating ART (tenofovir/emtricitabine plus atazanavir/ritonavir [ATV/r] or darunavir/ritonavir [DRV/r] or raltegravir [RAL]). Orthogonal partial least squares discriminant analysis was used to assess metabolites/lipid subspecies that discriminated between groups. Graphical lasso estimated group-specific metabolite/lipid subspecies networks associated with the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR). Correlations between inflammatory markers and metabolites/lipid subspecies were visualized using heat maps. RESULTS: Of 435 participants, 218 were PLHIV. Compared to HIV-seronegative individuals, ART-naive PLHIV exhibited higher levels of saturated triacylglycerols/triglycerides (TAGs) and 3-hydroxy-kynurenine, lower levels of unsaturated TAGs and N-acetyl-tryptophan, and a sparser and less heterogeneous network of metabolites/lipid subspecies associated with HOMA-IR. PLHIV on RAL vs ATV/r or DRV/r had lower saturated and unsaturated TAGs. Positive correlations were found between medium-long chain acylcarnitines (C14-C6 ACs), palmitate, and HOMA-IR for RAL but not ATV/r or DRV/r. Stronger correlations were seen for TAGs with interleukin 6 and high-sensitivity C-reactive protein after RAL vs ATV/r or DRV/r initiation; these correlations were absent in ART-naive PLHIV. CONCLUSION: Alterations in the metabolome/lipidome suggest increased lipogenesis for ART-naive PLHIV vs HIV-seronegative individuals, increased TAG turnover for RAL vs ATV/r or DRV/r, and increased inflammation associated with this altered metabolome/lipidome after initiating ART. Future studies are needed to understand cardiometabolic consequences of lipogenesis and inflammation in PLHIV.

Urinary Proadrenomedullin and Disease Severity in Children With Suspected Community-acquired Pneumonia.

BACKGROUND: Plasma proadrenomedullin (proADM) is a promising biomarker to predict disease severity in community-acquired pneumonia (CAP). Urinary biomarkers offer advantages over blood, including ease of collection. We evaluated the association between urinary proADM and disease severity in pediatric CAP. METHODS: We performed a prospective cohort study of children 3 months to 18 years with CAP. Urinary proADM/creatinine (Cr) was calculated. Disease severity was defined as: mild (discharged home), mild-moderate (hospitalized but not moderate-severe or severe), moderate-severe (eg, hospitalized with supplemental oxygen and complicated pneumonia) and severe (eg, vasopressors and invasive ventilation). Outcomes were examined using logistic regression within the cohort with suspected CAP and in a subset with radiographic CAP. RESULTS: Of the 427 children included, higher proADM/Cr was associated with increased odds of severe disease compared with nonsevere disease [suspected CAP, odds ratio (OR) 1.02 (95% confidence interval (CI) 1.003, 1.04); radiographic CAP, OR 1.03 (95% CI 1.01, 1.06)] when adjusted for other covariates. ProADM/Cr had an area under the receiver operating characteristic curve of 0.56 (threshold 0.9 pmol/mg) to differentiate severe from nonsevere disease in suspected CAP and 0.65 in radiographic CAP (threshold 0.82 pmol/mg). Healthy controls had less proADM in their urine (median, 0.61 pmol/mg) compared with suspected (0.87 pmol/mg, P = 0.018) and radiographic (0.73 pmol/mg, P = 0.016) CAP. CONCLUSIONS: Urinary proADM/Cr ratio measured at the time of emergency department visit was statistically associated with the development of severe outcomes in children with CAP, with stronger discriminatory performance in radiographic disease.

Neurocognitive, Quality of Life, and Behavioral Outcomes for Patients With Covert Stroke After Cardiac Surgery: Exploratory Analysis of Data From a Prospectively Randomized Trial.

BACKGROUND: Asymptomatic brain ischemic injury detected with diffusion-weighted magnetic resonance imaging (DWI) is reported in more than one-half of patients after cardiac surgery. There are conflicting findings on whether DWI-detected covert stroke is associated with neurocognitive dysfunction after surgery, and it is unclear whether such ischemic injury affects quality of life or behavioral outcomes. The purpose of this study was to perform exploratory analysis on whether covert stroke after cardiac surgery is associated with delayed neurocognitive recovery 1 month after surgery, impaired quality of life, anxiety, or depression. METHODS: Analysis of data collected in a prospectively randomized study in patients undergoing cardiac surgery testing whether basing mean arterial pressure (MAP) targets during cardiopulmonary bypass to be above the lower limit of cerebral autoregulation versus usual practices reduces the frequency of adverse neurological outcomes. A neuropsychological testing battery was administered before surgery and then 1 month later. Patients underwent brain magnetic resonance imaging (MRI) between postoperative days 3 and 5. The primary outcome was DWI-detected ischemic lesion; the primary end point was change from baseline in domain-specific neurocognitive Z scores 1 month after surgery. Secondary outcomes included a composite indicator of delayed neurocognitive recovery, quality of life measures, state and trait anxiety, and Beck Depression Inventory scores. RESULTS: Of the 164 patients with postoperative MRI data, clinical stroke occurred in 10 patients. Of the remaining 154 patients, 85 (55.2%) had a covert stroke. There were no statistically significant differences for patients with or without covert stroke in the change from baseline in Z scores in any of the cognitive domains tested adjusted for sex, baseline cognitive score, and randomization treatment arm. The frequency of delayed neurocognitive recovery (no covert stroke, 15.1%; covert stroke, 17.6%; P = .392), self-reported quality of life measurements, anxiety rating, or depression scores were not different between those with or without DWI ischemic injury. CONCLUSIONS: More than one-half of patients undergoing cardiac surgery demonstrated covert stroke. In this exploratory analysis, covert stroke was not found to be significantly associated with neurocognitive dysfunction 1 month after surgery; evidence of impaired quality of life, anxiety, or depression, albeit a type II error, cannot be excluded.

Abnormal Microarray, Clinical Outcomes, and Surgical Risk Scores in Young Children with Cardiac Disease.

The clinical implications of abnormal chromosomal microarray (CMA) remain unclear for children less than 1 year of age with critical heart disease. Our objective was to determine whether abnormal CMA was related to surgical severity scores or to pre-determined clinical outcomes, including cardiac arrest. Retrospective review of children under 1 year of age admitted to a pediatric cardiac intensive care unit from December, 2014 to September, 2017. Associations between CMA result and cardiac arrest, syndromic abnormalities, and extracardiac anomalies were evaluated. A simple and multivariable logistic regression model was used to analyze associations between STAT mortality category and CMA result. The overall prevalence of abnormal microarray was 48/168 (29%), with peak prevalence in AV septal defects and left-sided obstructive lesions. There was no statistical association between surgical severity scores and abnormal CMA (STAT 1/2 vs. 3+, odds ratio 0.56, p = 0.196). Abnormal CMA was associated with a higher prevalence of cardiac arrest (5/48 abnormal CMA vs. 2/120 normal CMA, p = 0.02). Abnormal CMA was associated with a higher frequency of syndromic abnormalities (18/48 abnormal CMA vs. 13/120 normal CMA, p < 0.001). There was a high prevalence of abnormal CMA findings in the pediatric cardiac population less than 1 year of age (29%), associated with cardiac arrest, but not associated with surgical risk score. The absence of a standardized protocol for ordering a CMA in the setting of congenital heart disease results in a highly variable prevalence data.

Dietary Fat and Fatty Acid Intake in Nulliparous Women: Associations with Preterm Birth and Distinctions by Maternal BMI.

BACKGROUND: Evidence documenting whether diet quality, particularly dietary fatty acids, is associated with preterm birth (PTB) is limited. OBJECTIVE: The aim was to measure associations between dietary fatty acid intake prior to pregnancy, specifically n-3 (É·-3) PUFAs and odds of PTB in US women and determine if associations differed by prepregnancy BMI. METHODS: We designed a secondary analysis of dietary intake in nulliparous women enrolled in a longitudinal cohort (NCT01322529). Participants completed an FFQ, modified to assess detailed PUFA intake, during the 3 mo preceding pregnancy. Inclusion in this analytic cohort required total energy intake within 2 SDs of the group mean. Prepregnancy BMI was categorized as underweight, normal, overweight, or obese. The primary exposure was estimated intake of EPA and DHA (combined EPA+DHA), in the context of a recommended intake of 250 mg. The primary outcome was PTB (<37 wk). Adjusted regression models controlled for maternal factors relevant to PTB and evaluated associations with PUFAs. Interaction terms estimated effect modification of BMI. A false discovery rate (FDR) correction accounted for multiple comparisons. RESULTS: Median daily intake of combined EPA+DHA in 7365 women was 70 mg (IQR: 32, 145 mg). A significant interaction term indicated the effects of EPA+DHA on odds of PTB were different for different BMI categories (P < 0.01). Specifically, higher intake of combined EPA+DHA was nominally associated with reduced odds of PTB in women with underweight (OR: 0.67; 95% CI: 0.46-0.98) and normal BMI (OR: 0.87; 95% CI: 0.78-0.96), yet was associated with increased odds of overweight BMI (OR: 1.21; 95% CI: 1.02-1.44). Associations remained significant after FDR correction. CONCLUSIONS: Based on a cohort of US women designed to identify predictors of adverse pregnancy outcomes, dietary intake of combined EPA+DHA was considerably lower than recommended. Associations between intake of these recommended n-3 fatty acids and risk of PTB differ by maternal BMI.

Surveillance Cultures and Infection in 230 Pacemaker and Defibrillator Generator Changes in Pediatric and Adult Congenital Patients.

BACKGROUND: Postoperative infections can occur during surgical replacement of pulse generators for pacemakers and implantable cardioverter-defibrillators. The incidence of infection is poorly documented in children and patients with adult congenital heart disease. The utility of surveillance cultures obtained from device pocket swabs is unknown in this group. METHODS: We reviewed surgical replacements of cardiovascular implantable pulse generators from 2010 to 2017. Two cohorts were defined. In a surveillance cohort (123 patients), aerobic and anaerobic culture swabs of the device pocket were obtained at the time of generator change. In a nonsurveillance cohort (107 patients), generator change occurred without obtaining cultures. RESULTS: During 230 generator changes (mean patient age 19 years; 77% with structural congenital heart disease), two clinical infections occurred at the surgical site (0.9% incidence). Neither infection occurred in the surveillance cohort. Cultures were positive in 12 (9.8%) of 123 patients in the surveillance cohort, but 11 of 12 were likely contaminants and none were subsequently associated with clinical disease. There was no association between clinical infection or positive surveillance cultures and the location of pulse generator, the presence of other concurrent surgeries, or a history of prior pocket infection. CONCLUSIONS: Clinical infection was rare after pulse generator change in children and young adults. No cases required reintervention on the pocket. Surveillance cultures did not improve clinical care. These data extend current recommendations that surveillance cultures are not required during generator change to the pediatric and young adult population.

Quantile regression on inactivity time.

The inactivity time, or lost lifespan specifically for mortality data, concerns time from occurrence of an event of interest to the current time point and has recently emerged as a new summary measure for cumulative information inherent in time-to-event data. This summary measure provides several benefits over the traditional methods, including more straightforward interpretation yet less sensitivity to heavy censoring. However, there exists no systematic modeling approach to inferring the quantile inactivity time in the literature. In this paper, we propose a semi-parametric regression method for the quantiles of the inactivity time distribution under right censoring. The consistency and asymptotic normality of the regression parameters are established. To avoid estimation of the probability density function of the inactivity time distribution under censoring, we propose a computationally efficient method for estimating the variance-covariance matrix of the regression coefficient estimates. Simulation results are presented to validate the finite sample properties of the proposed estimators and test statistics. The proposed method is illustrated with a real dataset from a clinical trial on breast cancer.

Challenging proximal hypospadias repairs: An evolution of technique for two stage repairs.

INTRODUCTION: Proximal hypospadias repair remains challenging. Our approach to the first stage of two-stage proximal hypospadias repairs has evolved from using Byars' flaps to preputial inlay grafts in anatomically suitable cases and pedicled preputial flaps in more complex repairs. We reviewed our outcomes, hypothesizing that inlay grafts and pedicled preputial flaps were associated with lower complication risks than Byars' flaps. STUDY DESIGN: A single institution, retrospective, cohort study of consecutive two-stage, primary, proximal hypospadias repairs performed from 2007 to 2017 was conducted. Patients with <6 months follow-up and incomplete operative reports were excluded. Risk of complications (fistula, dehiscence, diverticulum, meatal stenosis, stricture) were evaluated following urethroplasty and stratified by first-stage repair technique. As technique refinements have been made since 2012, comparisons between two temporal subgroups (those who underwent repair in 2007-2012 and in 2013-2017) were made. RESULTS: 78 of 127 patients met inclusion criteria. Overall complication rate was 47% (Summary Table). Median follow-up was 25.4 months (range 6.4-128.5 months) after urethroplasty. Pedicled preputial flaps (hazards ratio [HR] 0.30; 95% Confidence Interval [CI] 0.14-0.65) and inlay grafts (HR 0.32; 95% CI 0.11-0.95) were associated with lower complication risks compared to Byars' flaps (Summary Table). Median time to complication was significantly shorter for Byars' flaps (5.7 months) than for inlay grafts (40.6 months) and pedicled preputial flaps (79.2 months) by Kaplan Meier analysis. Temporal subgroup comparisons showed that overall complication rates decreased from 70% to 31% (p = 0.001), but differences in complication rates by first-stage technique were not statistically significant. DISCUSSION: In our cohort, repairs with Byars' flaps had the highest complication rate, which is consistent with our observations that urethras tubularized from Byars' flaps lack appropriate backing and are hypermobile and irregular. To overcome these shortcomings, modifications were made to our approach to two-stage proximal hypospadias repairs with the use of inlay grafts and pedicled preputial flaps quilted to the underlying corporal bodies to optimize the stability of the urethral plate. Our preliminary results are promising. CONCLUSION: Approach to the first stage of two-stage repairs affects outcomes. Pedicled preputial flaps and inlay grafts were associated with lower complication risks than Byars' flaps. Refinement of technique and patient selection may have resulted in fewer complications in the short term. However, long-term follow-up is needed.

Persistence of Palpitations After Slow Pathway Modification for AVNRT in Young People.

Symptoms are the most common indication for ablation in children with atrioventricular nodal reentrant tachycardia (AVNRT). After the procedure, patients may continue to report palpitations. The objective of this study was to quantify the risk and duration of palpitations after pediatric slow pathway modification as well as demographic and technical associations. This was a retrospective review of consecutive patients at a pediatric center who underwent slow pathway modification for AVNRT from 2012 to 2018. Patients with a prior ablation attempt or congenital heart disease were excluded. Palpitations were documented in 35% of patients after ablation. Neither post-ablation echo beats nor other evidence of residual dual AV nodal physiology were associated with a higher risk of post-ablation palpitations. Of the 35 patients with post-ablation palpitations, the median time to resolution of palpitations was 48 months. Acute procedural success was achieved in all 100 cases. There were two recurrences of AVNRT during long-term follow-up and one instance of ectopic atrial tachycardia (3% SVT recurrence). Palpitations after AVNRT ablation occurred in approximately one-third of cases, despite a low recurrence of true arrhythmia. Prior to ablation, patients and families should be counseled that post-ablation palpitations are common and AVNRT recurrence is rare.

Variability in Kidney Function Estimates in Emerging Adults With Spina Bifida: Implications for Transitioning From Pediatric to Adult Care.

OBJECTIVE: To examine the variability of estimated glomerular filtration rate (eGFR) in emerging adults with spina bifida (SB) by comparing multiple equations across the transitional age period, hypothesizing that creatinine (Cr)-based equations show greater variability than cystatin-C (CysC)- or combination-based equations. METHODS: A retrospective cohort study was performed from 2012 to 2017 at a multidisciplinary SB clinic. Emerging adults were defined as patients ages 18-28 years old. Four pediatric, 3 adult, and 3 averaged eGFR equations were considered. Cross-sectional variability in eGFR data was assessed using coefficients of variation, chronic kidney disease (CKD) stage classification, and pairwise percent relative difference in eGFR between analogous pediatric and adult equations based on included lab values. Longitudinal changes in eGFR over time were compared across equations using a covariance pattern model accounting for repeated measures. RESULTS: Seventy-five emerging adults with SB (median age 21.8 years; 55% female; 83% with myelomeningocele) were included in cross-sectional analyses. Adult equations gave higher median eGFRs by 22%-27% and generally milder CKD stage classification than analogous pediatric equations. In longitudinal analyses (median follow-up of 22 months), all equations conferred negative eGFR changes over time (range -1.9 to -4.3 mL/min/1.73m2 per year) that were not significantly different. CONCLUSION: In emerging adults with SB, adult equations demonstrated higher median eGFRs by 22%-27% compared to analogous pediatric equations, even with Cystatin-C, and generally downstaged CKD stage classification. The same eGFR equation should be used for serial kidney function monitoring in emerging adults with SB who transition care from pediatric to adult services.