Changes in estimated glomerular filtration rate over the first year following repeat heart transplant in children and young adults.

BACKGROUND: Renal function is reduced in patients undergoing heart transplant due to hemodynamic compromise, cardiorenal syndrome, and nephrotoxin exposure. No current studies evaluate renal function in retransplants. METHODS: We reviewed all heart transplants at our center from 1995 to 2021 and matched first-time heart transplants with retransplants, based on age at transplant, sex, and race. Estimated glomerular filtration rate (eGFR) was derived from CKiD-U25 calculator using creatinine and measured prior to transplant, 1-week post-transplant, 1-3, 6, and 12 months post-transplant, and recent follow-up. Changes in eGFR were measured within and between patients using a piecewise linear mixed effect model with matching. Exploratory univariate analysis was performed to evaluate pre-transplant risk factors for decreased eGFR. RESULTS: The unmatched cohort included 393 heart transplant recipients, with 47 being retransplants. Thirty-eight patients in both groups with at least 1 year of follow-up underwent matching. Both retransplants and first-time transplants had an initial decline in eGFR. eGFR rebounded to baseline or above baseline at 1-3 months post-transplant, but eGFR in retransplants remained significantly lower. At 1-year post-transplant, the average eGFR was 67.8 ± 4.3 mL/min/1.73 m2 versus 104.7 ± 4.3 mL/min/1.73 m2 (p < .001) in the retransplants and first-time transplants group, respectively. CONCLUSION: This study provides data on anticipated renal trajectory following retransplantation.

Maternal-fetal comorbidities and obstetrical outcomes of fetal single ventricle cardiac defects: 10 years' experience with a multidisciplinary management protocol at a single center.

OBJECTIVES: To describe and compare maternal and fetal comorbidities and obstetrical outcomes in pregnancies with hypoplastic left and right heart (HLHS and HRH) single ventricle cardiac defects (SVCD) from a single center under a multidisciplinary protocol. METHOD: A single center retrospective review of fetal SVCD from 2013 to 2022. Maternal-fetal comorbidities, delivery, and postnatal outcomes were compared between HLHS and HRH using descriptive statistics and univariate and multivariate analyses. RESULTS: Of 181 SVCD pregnancies (131 HLHS; 50 HRH), 9% underwent termination, 4% elected comfort care, 5 died in utero and 147/152 liveborns survived to the first cardiac intervention. Cesarean delivery occurred in 57 cases (37%), planned in 36 and unplanned in 21. Comorbidities, which did not differ between HLHS and HRH, included fetal growth restriction (FGR, 17%), prematurity (14%), maternal hypertension (9%), maternal obesity (50%), fetal extracardiac anomalies and chromosome anomalies (12%, 13%). In multivariate analysis, only earlier gestational age at delivery and oligohydramnios predicted decreased odds of survival at one year. CONCLUSION: Maternal-fetal comorbidities are common in both HLHS and HRH. Earlier gestational age at delivery and oligohydramnios predict lower postnatal survival. FGR, even with severe early onset, did not significantly impact short- or long-term neonatal survival in single ventricle conditions.

Measurement of Physical Activity by Actigraphy in Infants and Young Children with Pulmonary Arterial Hypertension.

OBJECTIVE: To evaluate the feasibility, tolerability, and adherence with wearable actigraphy devices among infants and children with pulmonary arterial hypertension (PAH). STUDY DESIGN: This multicenter, prospective, observational study included children ages 0-6 years with and without PAH. Participants wore the ActiGraph wGT3X-BT on the hip and FitBit Inspire on the wrist during waking hours for 14 days. Steps, vector magnitude counts per minute, activity intensity, heart rate, and heart rate variability were compared between groups. RESULTS: Forty-seven participants (18 PAH, 29 control) were enrolled from 10 North American sites. PAH patients were mostly functional class II (n = 16, 89%) and treated with oral medications at the time of enrollment. The number of wear days was not significantly different between the groups (ActiGraph: 10 [95% CI: 5.5, 12.2] in PAH vs 8 [4, 12] in control, P = .20; FitBit 13 [10, 13.8] in PAH vs 12 [8, 14] in control, P = .87). Complete data were obtained in 81% of eligible ActiGraph participants and 72% of FitBit participants. PAH participants demonstrated fewer steps, lower vector magnitude counts per minute, more sedentary activity, and less intense physical activity at all levels compared with control participants. No statistically significant differences in heart rate variability were demonstrated between the 2 groups. CONCLUSIONS: Measurement of physical activity and other end points using wearable actigraphy devices was feasible in young children with PAH. Larger studies should determine associations between physical activity and disease severity in young patients with PAH to identify relevant end points for pediatric clinical trials.

Dots and spots: A retrospective review of T2-hyperintense white matter lesions in pediatric patients with and without headache.

OBJECTIVE: We aimed to determine if T2-weighted hyperintense white matter lesions (WMLs) on brain magnetic resonance imaging (MRI) occur more frequently in pediatric patients with migraine and other primary headache disorders compared to the general pediatric population. BACKGROUND: Small foci of T2 hyperintensity in the white matter are frequently identified on brain MRI during the workup of pediatric headache. Such lesions have been reported to be more common among adults with migraine versus adults without migraine; however, this association has not been well established in the pediatric population. METHODS: We performed a retrospective cross-sectional single-center study of electronic medical records and radiologic studies, examining pediatric patients from 3 to 18 years old who underwent brain MRI between 2016 and 2021. Patients with existing intracranial disease or abnormalities were excluded. Patients with reports of headache were categorized. Imaging was reviewed to determine the number and location of WMLs. Headache-associated disability scores (Pediatric Migraine Disability Assessment) were noted, when available. RESULTS: Brain MRI of 248 patients with a diagnosis of headache (144 with migraine, 42 with non-migraine primary headache, and 62 with headache that could not be further classified) and 490 controls were reviewed. WMLs were encountered commonly among all study participants, with a prevalence of 40.5% (17/42) to 54.1% (265/490). There was no statistically significant difference comparing the number of lesions between each of the headache groups and the control group: migraine group versus control group median [interquartile range (IQR)], 0 [0-3] versus 1 [0-4], incidence rate ratio [95% confidence interval (CI)], 0.99 [0.69-1.44], p = 0.989, non-migraine headache group versus control group median [IQR], 0 [0-3] versus 1 [0-4], 0.71 [0.46-1.31], p = 0.156, headache not otherwise specified group versus control group median [IQR], 0 [0-4] versus 1 [0-4], 0.77 [0.45-1.31], p = 0.291. There was no significant correlation between headache-associated disability and the number of WMLs (0.07 [-0.30 to 0.17], rho [95% CI]). CONCLUSION: T2 hyperintense WMLs are common within the pediatric population and are not encountered more frequently in pediatric patients with migraine or other primary headache disorders. Thus, such lesions are presumably incidental and unlikely related to headache history.

Using the Ages & Stages Questionnaire to assess later effects of an infant intervention promoting language in primary care.

BACKGROUND: Positive relational experiences during infancy have a profound impact on child development and are critical for future health and school readiness. We have been evaluating a simple finger puppet intervention that takes one minute and costs $1USD to deliver in the primary care setting to promote caregiver-infant interactions. We explored using developmental trajectories to determine later outcomes of our early intervention program by comparing trajectories to age 36 months to assess optimal intervention timing when delivered in early versus late infancy. METHODS: Three cohorts were enrolled and given a puppet at 2 months (early intervention) and 6 or 12 months (late intervention). Child development was assessed using the Ages & Stages Questionnaires (ASQ-3), which were independently collected during well visits. Scanned ASQ-3 forms from 2 to 36 months were obtained retrospectively through the electronic medical record. To compare longitudinal scores at different ages, all raw scores were first converted to z-scores. Longitudinal mixed effects models examined the trajectories of participant ASQ-3 scores over time by comparing the average intercepts and slopes. RESULTS: Of 180 children enrolled, 172 (96%) completed 2 or more ASQ-3 questionnaires and were included in the analysis, with a mean of 4.9 and a total of 843 questionnaires. Most children (85%) were on government-sponsored insurance. There were no statistical differences comparing cohort intercepts, while early intervention had a significant difference in slope compared to late intervention for the Personal-Social domain (0.12, p=0.018), resulting in higher predicted scores at 36 months. Early compared to late intervention had a difference in slope approaching significance for Communication (0.14, p=0.056) and the combined non-motor score (0.33, p=0.052). There were no significant differences in slope for Problem Solving (0.05, p=0.48), Gross Motor (-0.009, p=0.84), Fine Motor (0.06, p=0.22), and total ASQ-3 (0.32, p=0.17) scores. CONCLUSIONS: Finger puppets may provide a simple and scalable way to encourage responsive caregiver-infant interactions promoting language and social-emotional development, especially when provided in early versus late infancy. Our trajectory analysis also demonstrates a useful and potentially cost-effective approach to evaluating long-term developmental outcomes of an early intervention.

Impact on Maternal Postpartum Depressive Symptoms of a Primary Care Intervention Promoting Early Language: A Pilot Study.

OBJECTIVES: Maternal depressive symptoms are an important risk factor for adverse child outcomes, especially in the perinatal period. We studied whether introducing finger puppets in the primary care setting to promote infant language improves maternal postpartum depressive symptoms. METHODS: An intervention cohort was enrolled and given a finger puppet at the 2-month infant well visit. Two usual care cohorts were enrolled at either the 6- or 12-month well visit as part of a larger study. Depressive symptoms were assessed using the Edinburgh Postnatal Depression Scale (EPDS), which was administered by clinic providers as part of routine screening done at both the 2- and 4-month well visits. EPDS scores were obtained retrospectively through the electronic medical record. RESULTS: Included mothers (n = 127) completed the EPDS at 2 and 4 months postpartum. Most children (83%) were on government-sponsored insurance. Mean EPDS scores and scores classified as possible depression (≥ 10) did not differ between cohorts. However, the change in scores between visits was significantly different for intervention (n = 46) compared to usual care (n = 81) participants (-1.1 vs. +0.4, p = 0.001). More intervention scores improved (n = 17, 37%) compared to usual care (n = 14, 17%), while more usual care scores worsened (n = 28, 35%) compared to intervention (n = 6, 13%) (p = 0.008). CONCLUSION: Finger puppets introduced during infant primary care visits to support language-rich maternal-infant interactions may provide a simple, low-cost way to improve maternal postpartum depressive symptoms. Larger studies with more diverse populations are needed to determine if effects are replicable, generalizable, and translate into better clinical outcomes.

Submaximal Exercise Response is Associated with Future Hypertension in Patients with Coarctation of the Aorta.

Hypertension (HTN) is common in patients with a history of coarctation of the aorta (CoA) and remains underrecognized and undertreated. Studies in the non-coarctation otherwise healthy adult population have correlated an exaggerated blood pressure response during mild to moderate exercise with subsequent diagnosis of HTN. The goal of this study was to determine if blood pressure response to submaximal exercise in normotensive CoA patients correlated with development of HTN.Retrospective chart review was performed in individuals ≥ 13 years old with CoA and no diagnosis of HTN at time of cardiopulmonary exercise testing (CPET). Systolic blood pressure (SBP) during CPET at rest, submax 1 (stage 1 Bruce or minute 2 bicycle ramp), submax 2 (stage 2 Bruce or minute 4 bicycle ramp), and peak were recorded. The primary composite outcome was HTN diagnosis or initiation of anti-hypertensive medications at follow up.There were 177 patients (53% female, median age 18.5 years), of whom 38 patients (21%) met composite outcome during a median follow up of 46 months. Men were more likely to develop hypertension. Age at repair and age at CPET were not significant covariates. At each stage of CPET, SBP was significantly higher in those who met the composite outcome. Submax 2 SBP ≥ 145 mmHg was 75% sensitive, 71% specific in males and 67% sensitive, 76% specific in females for development of composite outcome.Our study shows an exaggerated SBP response to submaximal exercise may portend an increased risk of developing hypertension during short- to mid-term follow up.

Peripheral Vasoactive Administration in Critically Ill Children With Shock: A Single-Center Retrospective Cohort Study.

OBJECTIVES: Management of fluid refractory pediatric shock requires prompt administration of vasoactive agents. Although delivery of vasoactive therapy is generally provided via a central venous catheter, their placement can delay drug administration and is associated with complications. We characterize peripheral vasoactive administration in a cohort of critically ill children with shock, evaluate progression to central venous catheter placement, and describe complications associated with extravasation. DESIGN: Retrospective cohort study. SETTING: Single-center, quaternary PICU (January 2010 to December 2015). PATIENTS: Children (31 d to 18 yr) who received epinephrine, norepinephrine, or dopamine. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We compared patients based on the initial site of vasoactive infusion: peripheral venous access (PVA) or central venous access (CVA) and, within the PVA group, compared patients based on subsequent placement of a central catheter for vasoactive infusion. We also characterized peripheral extravasations. We evaluated 756 patients: 231 (30.6%) PVA and 525 (69.4%) CVA patients. PVA patients were older, had lower illness severity, and more frequently had vasoactive therapy initiated at night compared with CVA patients. In PVA patients, 124 (53.7%) had a central catheter placed after a median of 140 minutes (interquartile range, 65-247 min) of peripheral treatment. Patients who avoided central catheter placement had lower illness severity. Of the 93 patients with septic shock, 44 (47.3%) did not have a central catheter placed. Extravasations occurred in four of 231 (1.7% [95% CI, 0.03-3.4]) PVA patients, exclusively in the hand. Three patients received pharmacologic intervention, and none had long-term disabilities. CONCLUSIONS: In our experience, peripheral venous catheters can be used for vasoactive administration. In our series, the upper limit of the 95% CI for extravasation is approximately 1-in-30, meaning that this route may be an appropriate option while evaluating the need for central access, particularly in patients with low illness severity.

Development and Evaluation of the Pediatric Readiness for Discharge (P-REDI) Tool.

PURPOSE: The purpose of this study was to evaluate the P-REDI discharge tool for safe discharge to home following ambulatory surgery. DESIGN: A quasi-experimental, mixed methods with pre/post nurse surveys and retrospective chart review comparing pre-, interim- and post-implementation of P-REDI on unscheduled clinic visits, Emergency Department visits, hospital readmission, and length of stay. METHODS: The P-REDI tool was developed in collaboration with anesthesia and based upon an extensive review of the literature on safe discharge from the Phase II Postanesthesia Care Unit (PACU). Nurse surveys and patient data extracted from the electronic health record through the computer-assisted reporting system were analyzed using descriptive statistics, bivariate statistics, and correlations to assess outcomes and relationships between variables. FINDINGS: Nurses' perceptions of discharge criteria improved after implementation of P-REDI. There were no differences in adverse events before, during, and after the implementation of the P-REDI instrument. There was a significant decrease in Phase II time after implementation of the tool. There were also significant correlations with the P-REDI score and related variables such as length of surgical procedure time and length of stay. CONCLUSIONS: The P-REDI tool was developed to provide nurses a concrete, objective tool to increase their level of comfort with discharging patients from the Phase II PACU. The tool significantly decreased length of stay in Phase II without any change in adverse events. The cost savings to the institution needs to be examined in future studies.

Anesthesia for Maternal-Fetal Interventions: A Survey of Fetal Therapy Centers in the North American Fetal Therapy Network.

INTRODUCTION: A wide range of fetal interventions are performed across fetal therapy centers (FTCs). We hypothesized that there is significant variability in anesthesia staffing and anesthetic techniques. METHODS: We conducted an online survey of anesthesiology directors at every FTC within the North American Fetal Therapy Network (NAFTNet). The survey included details of fetal interventions performed in 2018, anesthesia staffing models, anesthetic techniques, fetal monitoring, and postoperative management. RESULTS: There was a 92% response rate. Most FTCs are located within an adult hospital and employ a small team of anesthesiologists. There is heterogeneity when evaluating anesthesiology fellowship training and staffing, indicating there is a multidisciplinary specialty team-based approach even within anesthesiology. Minimally invasive fetal interventions were the most commonly performed. The majority of FTCs also performed ex utero intrapartum treatment (EXIT) and open mid-gestation procedures under general anesthesia (GA). Compared to FTCs only performing minimally invasive procedures, FTCs performing open fetal procedures were more likely to have a pediatric surgeon as director and performed more minimally invasive procedures. CONCLUSIONS: There is considerable variability in anesthesia staffing, caseload, and anesthetic techniques among FTCs in NAFTNet. Most FTCs used maternal sedation for minimally invasive procedures and GA for EXIT and open fetal surgeries.

Activation of kynurenine pathway of tryptophan metabolism after infant cardiac surgery with cardiopulmonary bypass: a prospective cohort study.

BACKGROUND: Serum kynurenic acid is associated with poor outcomes after infant cardiopulmonary bypass (CPB), but comprehensive mapping of the kynurenine pathway (KP) after CPB has yet to be performed. AIMS: To map changes in the KP induced by infant CPB. METHODS: Compared changes in serum KP metabolites through 48hrs post-op with liquid-chromatography-tandem mass spectrometry. RESULTS: Infant CPB results in marked increase in proximal, but not distal metabolites of the KP. CONCLUSIONS: Infant CPB leads to accumulation of circulating KP metabolites, which have important neurologic and immunologic activities. Thus, further exploration of the KP is warranted in these high-risk infants.

DNA Methylation Changes in Lung Immune Cells Are Associated with Granulomatous Lung Disease.

Epigenetic marks are likely to explain variability of response to antigen in granulomatous lung disease. The objective of this study was to identify DNA methylation and gene expression changes associated with chronic beryllium disease (CBD) and sarcoidosis in lung cells obtained by BAL. BAL cells from CBD (n = 8), beryllium-sensitized (n = 8), sarcoidosis (n = 8), and additional progressive sarcoidosis (n = 9) and remitting (n = 15) sarcoidosis were profiled on the Illumina 450k methylation and Affymetrix/Agilent gene expression microarrays. Statistical analyses were performed to identify DNA methylation and gene expression changes associated with CBD, sarcoidosis, and disease progression in sarcoidosis. DNA methylation array findings were validated by pyrosequencing. We identified 52,860 significant (P < 0.005 and q < 0.05) CpGs associated with CBD; 2,726 CpGs near 1,944 unique genes have greater than 25% methylation change. A total of 69% of differentially methylated genes are significantly (q < 0.05) differentially expressed in CBD, with many canonical inverse relationships of methylation and expression in genes critical to T-helper cell type 1 differentiation, chemokines and their receptors, and other genes involved in immunity. Testing of these CBD-associated CpGs in sarcoidosis reveals that methylation changes only approach significance, but are methylated in the same direction, suggesting similarities between the two diseases with more heterogeneity in sarcoidosis that limits power with the current sample size. Analysis of progressive versus remitting sarcoidosis identified 15,215 CpGs (P < 0.005 and q < 0.05), but only 801 of them have greater than 5% methylation change, demonstrating that DNA methylation marks of disease progression changes are more subtle. Our study highlights the significance of epigenetic marks in lung immune response in granulomatous lung disease.

Estimated Cost Savings: Everyone With Diabetes Counts (EDC) Program.

Everyone with Diabetes Counts (EDC) is a national disparities reduction program funded by the Centers for Medicare & Medicaid Services to improve outcomes in the underserved minority, diverse, and rural populations. This analysis evaluates West Virginia's pilot program of diabetes self-management education (DSME), one component of EDC. We frequency-matched 422 DSME completers to 1688 others by demographics and enrollment from Medicare fee-for service claims. We estimated savings associated with reduced hospitalizations in multivariable negative binomial models. DSME completers had 29% fewer hospitalizations (adjusted P < .0069). We estimated savings of $35 900 per 100 DSME completers in West Virginia.

Beryllium-induced lung disease exhibits expression profiles similar to sarcoidosis.

A subset of beryllium-exposed workers develop beryllium sensitisation (BeS) which precedes chronic beryllium disease (CBD). We conducted an in-depth analysis of differentially expressed candidate genes in CBD.We performed Affymetrix GeneChip 1.0 ST array analysis on peripheral blood mononuclear cells (PBMCs) from 10 CBD, 10 BeS and 10 beryllium-exposed, nondiseased controls stimulated with BeSO4 or medium. The differentially expressed genes were validated by high-throughput real-time PCR in this group and in an additional group of cases and nonexposed controls. The functional roles of the top candidate genes in CBD were assessed using a pharmacological inhibitor. CBD gene expression data were compared with whole blood and lung tissue in sarcoidosis from the Gene Expression Omnibus.We confirmed almost 450 genes that were significantly differentially expressed between CBD and controls. The top enrichment of genes was for JAK (Janus kinase)-STAT (signal transducer and activator of transcription) signalling. A JAK2 inhibitor significantly decreased tumour necrosis factor-α and interferon-γ production. Furthermore, we found 287 differentially expressed genes overlapped in CBD/sarcoidosis. The top shared pathways included cytokine-cytokine receptor interactions, and Toll-like receptor, chemokine and JAK-STAT signalling pathways.We show that PBMCs demonstrate differentially expressed gene profiles relevant to the immunnopathogenesis of CBD. CBD and sarcoidosis share similar differential expression of pathogenic genes and pathways.

Galectin-3 levels are associated with right ventricular functional and morphologic changes in pulmonary arterial hypertension.

The response of the right ventricle (RV) to pulmonary arterial hypertension (PAH) involves changes in contractile function, chamber size, hypertrophy, and extracellular matrix (ECM). Galectin-3 (Gal-3) is a mediator of myocardial ECM metabolism and biomarker for left heart remodeling, yet its ability to reflect RV remodeling is unknown. We hypothesized that serum Gal-3 levels correlate with RV morphology and function in PAH, and that Gal-3 is associated with circulating markers of ECM. Fifteen subjects with PAH and 10 age-matched controls underwent same-day echocardiography, cardiac magnetic resonance (CMR) imaging, and phlebotomy for Gal-3 and ECM biomarkers including N-terminal propeptide of type III collagen type (PIIINP), tissue inhibitor of metalloproteinase-1 (TIMP-1), and hyaluronic acid (HA). RV ejection fraction, end diastolic volume index, end systolic volume index, and mass index were calculated using CMR. Echocardiography was used to estimate RV systolic pressure and measure RV strain. Serum Gal-3, TIMP-1, and HA levels were all significantly increased in PAH subjects when compared to controls. Gal-3 correlated with RV ejection fraction (ρ -0.44, p 0.03), end diastolic volume index (ρ 0.42, p 0.03), end systolic volume index (ρ 0.44, p 0.027), mass index (ρ 0.47, p 0.016), systolic pressure (ρ 0.55, p < 0.001), and strain (ρ 0.43, p 0.03). Gal-3 levels positively correlated with the ECM markers TIMP-1 and HA but not with PIIINP. In conclusion, Gal-3 levels are associated with multiple indices of RV function and morphology. Gal-3 may represent a novel biomarker for RV remodeling and associated ECM turnover in PAH.

Vorticity is a marker of right ventricular diastolic dysfunction.

Right ventricular diastolic dysfunction (RVDD) is an important prognostic indicator in pulmonary arterial hypertension (PAH). RV vortex rings have been observed in healthy subjects, but their significance in RVDD is unknown. Vorticity, the local spinning motion of an element of fluid, may be a sensitive measure of RV vortex dynamics. Using four-dimensional (4D) flow cardiac magnetic resonance imaging (CMR), we investigated the relationship between right heart vorticity with echocardiographic indexes of RVDD. Thirteen (13) PAH subjects and 10 controls underwent same-day 4D flow CMR and echocardiography. RV diastolic function was assessed using trans-tricuspid valve (TV) early (E) and late (A) velocities, E/A ratio, and e' and a' tissue Doppler velocities. RV and right atrial (RA) integrated mean vorticity was calculated for E and A-wave filling periods using 4D datasets. Compared with controls, A-wave vorticity was significantly increased in RVDD subjects in both the RV [2343 (1,559-3,295) vs. 492 (267-2,649) 1/s, P = 0.028] and RA [30 (27-44) vs. 9 (5-27) 1/s, P = 0.005]. RA E vorticity was significantly decreased [13 (7-22) vs. 28 (15-31) 1/s, P = 0.038] in RVDD. E-wave vorticity correlated TV e', E-,and TV E/A (P < 0.05), and A-wave vorticity associated with both TV A and E/A (P < 0.02). RVDD is associated with alterations in E- and A-wave vorticity, and vorticity correlates with multiple echocardiographic markers of RVDD. Vorticity may be a robust noninvasive research tool for the investigation of RV fluid and tissue mechanical interactions in PAH.

Chronic beryllium disease, HLA-DPB1, and the DP peptide binding groove.

Multiple epidemiologic studies demonstrate associations between chronic beryllium disease (CBD), beryllium sensitization (BeS), and HLA-DPB1 alleles with a glutamic acid residue at position 69 (E69). Results suggest that the less-frequent E69 variants (non-*0201/*0202 alleles) might be associated with greater risk of CBD. In this study, we sought to define specific E69-carrying alleles and their amino acid sequences in the DP peptide binding groove, as well as their relationship to CBD and BeS risk, using the largest case control study to date. We enrolled 502 BeS/CBD subjects and 653 beryllium-exposed controls from three beryllium industries who gave informed consent for participation. Non-Hispanic white cases and controls were frequency-matched by industry. HLA-DPB1 genotypes were determined using sequence-specific primer PCR. The E69 alleles were tested for association with disease individually and grouped by amino acid structure using logistic regression. The results show that CBD cases were more likely than controls to carry a non-*02 E69 allele than an *02 E69, with odds ratios (95% confidence interval) ranging from 3.1 (2.1-4.5) to 3.9 (2.6-5.9) (p < 0.0001). Polymorphic amino acids at positions 84 and 11 were associated with CBD: DD versus GG, 2.8 (1.8-4.6), p < 0.0001; GD versus GG, 2.1 (1.5-2.8), p < 0.0001; LL versus GG, 3.2 (1.8-5.6), p < 0.0001; GL versus GG, 2.8 (2.1-3.8), p < 0.0001. Similar results were found within the BeS group and CBD/BeS combined group. We conclude that the less frequent E69 alleles confer more risk for CBD than does *0201. Recent studies examining how the composition and structure of the binding pockets influence peptide binding in MHC genes, as well of studies showing the topology of the TCR to likely bind DPB1 preferentially, give plausible biological rationale for these findings.

Health-related quality of life over time in children with eosinophilic esophagitis and their families.

OBJECTIVES: Existing treatments for pediatric eosinophilic esophagitis (EoE) effectively reduce inflammation. The impact of treatment on health-related quality of life (HRQoL) over time for pediatric patients with EoE and their families, however, has not been systematically assessed. We hypothesized that individualized multidisciplinary treatment would improve both child and family HRQoL over time, with improvements associated with decreased symptom severity. METHODS: Children with EoE treated in 4 tertiary care centers were enrolled. Baseline assessments occurred at the time of patients' first evaluation; follow-up assessments occurred at 2 and 6 months after baseline. Presence and severity of 8 EoE symptoms were measured. HRQoL was measured with the Pediatric Quality of Life Inventory parent proxy report, child self-report (CR), and Family Impact Module (FIM). Statistical analyses used mixed-effects modeling to test changes over time for child and family HRQoL. RESULTS: Ninety-seven children were enrolled (ages 2-18 years, mean age 7.7 years ±â€Š4.8, 78% boys, 80% white). Baseline mean symptom number was 3.5 (standard deviation 2.3), and symptom severity was 5.5 (standard deviation, 4.5). HRQoL scores were significantly related to symptom scores (P < 0.001). EoE symptom severity decreased during the study (P = 0.03). Pediatric Quality of Life Inventory parent proxy Total and FIM Total scores improved from baseline to 6 months (respectively, adjusted means 78.4 vs 81.0, P = 0.0006; 68.9 vs 70.1, P = 0.03). Interactions with baseline symptom severity revealed that subjects with lowest symptom severity showed the most improved HRQoL scores (P = 0.0013). CONCLUSIONS: HRQoL improved during the course of evaluation and treatment, with positive changes being strongest for patients with less symptom severity at baseline.

Cystatin C: a potential biomarker for pulmonary arterial hypertension.

BACKGROUND AND OBJECTIVE: Cystatin C (CysC), a novel marker of renal function, predicts left heart failure and cardiovascular mortality. The hypothesis that serum CysC levels correlate with right ventricular (RV) morphology, function and pressure in pulmonary arterial hypertension (PAH) was tested. METHODS: As part of a prospective study, 14 PAH subjects and 10 matched controls underwent same-day echocardiography, cardiac magnetic resonance imaging (CMR), and phlebotomy for CysC, brain natriuretic peptide (BNP), and N-terminal BNP (NT-ProBNP). RV ejection fraction (RVEF), end-diastolic volume, end-systolic volume and mass were calculated using CMR. RV systolic pressure (RVSP), strain and diastolic function (including tricuspid valve (TV) E velocity, A velocity, e' velocity, E/A ratio and E/e' ratio) were assessed using echocardiography. RESULTS: RVSP was significantly elevated in PAH subjects versus controls (57 ± 17 vs. 28 ± 8 mm Hg, P < 0.0001). CysC was abnormally elevated in the PAH cohort when compared with controls (1.00 ± 0.23 vs 0.78 ± 0.05 mg/L, P = 0.001). CysC positively correlated with RVSP (rho 0.61, P = 0.002), RV end-diastolic volume (rho 0.50, P = 0.01), RV end-systolic volume (rho 0.58, P = 0.003), mass index (rho 0.66, P = 0.0004), strain (rho 0.51, P = 0.01) and strain rate (rho 0.51, P = 0.01) and negatively correlated with RVEF (rho -0.58, P = 0.003) and TV e' (rho -0.75, P < 0.0001). The same correlations with BNP and NT-ProBNP were comparable with CysC. CONCLUSIONS: In a small cohort, CysC accurately correlates with RV pressure, function and morphology. CysC may represent a novel PAH biomarker.

Mixed Methods Evaluation of the Impact of the COVID-19 Pandemic on Immigrant Families.

Introduction: Little is known about the experiences of immigrant families with COVID-19 illness. This mixed methods study compared child and household experiences at the time of a child's COVID-19 diagnosis between immigrant and US-born parents and explored immigrant Latino perspectives on underlying causes of COVID-19 disparities between immigrant and US-born families. Methods: Study data includes surveys of parents of a child with a positive SARS-CoV2 test resulting at Children's Hospital Colorado and focus groups with Latino immigrant adults. We compared household COVID-19 experiences, use of mitigation measures, vaccine intention and sociodemographic information between survey participants stratified by nativity and completed thematic qualitative data analysis. Results: Findings from quantitative data were reinforced by qualitative data including: lower socio-economic status and higher employment in essential services increased infections and spread in immigrant families and higher risk of limited information access related to language barriers and prevalent misinformation. Survey results showed no difference in COVID-19 vaccine intention by nativity. Focus group participants reported limited access to non-English language culturally-tailored vaccine information and competing work demands decreased uptake. Conclusion: Avoiding exacerbating disparities in the face of another public health emergency requires focused investments in policies and approaches specifically directed at immigrant communities.