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  • Ovid Technologies (Wolters Kluwer Health)  (45)
  • 1
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    Online Resource
    Short Gut Syndrome : Treatment by Neovascularization of the Small Intestine
    Ovid Technologies (Wolters Kluwer Health) ; 1996
    In:  Annals of Plastic Surgery Vol. 37, No. 1 ( 1996-07), p. 84-90
    Details
    In: Annals of Plastic Surgery, Ovid Technologies (Wolters Kluwer Health), Vol. 37, No. 1 ( 1996-07), p. 84-90
    Type of Medium: Online Resource
    ISSN: 0148-7043
    URL: Article
    DOI: 10.1097/00000637-199607000-00013
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 1996
    detail.hit.zdb_id: 2063013-X
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  • 2
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    Cardiomyopathy in Children: Classification and Diagnosis: A Scientific Statement From the American Heart Association
    Ovid Technologies (Wolters Kluwer Health) ; 2019
    In:  Circulation Vol. 140, No. 1 ( 2019-07-02)
    Details
    In: Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 140, No. 1 ( 2019-07-02)
    Abstract: In this scientific statement from the American Heart Association, experts in the field of cardiomyopathy (heart muscle disease) in children address 2 issues: the most current understanding of the causes of cardiomyopathy in children and the optimal approaches to diagnosis cardiomyopathy in children. Cardiomyopathies result in some of the worst pediatric cardiology outcomes; nearly 40% of children who present with symptomatic cardiomyopathy undergo a heart transplantation or die within the first 2 years after diagnosis. The percentage of children with cardiomyopathy who underwent a heart transplantation has not declined over the past 10 years, and cardiomyopathy remains the leading cause of transplantation for children 〉 1 year of age. Studies from the National Heart, Lung, and Blood Institute–funded Pediatric Cardiomyopathy Registry have shown that causes are established in very few children with cardiomyopathy, yet genetic causes are likely to be present in most. The incidence of pediatric cardiomyopathy is ≈1 per 100 000 children. This is comparable to the incidence of such childhood cancers as lymphoma, Wilms tumor, and neuroblastoma. However, the published research and scientific conferences focused on pediatric cardiomyopathy are sparcer than for those cancers. The aim of the statement is to focus on the diagnosis and classification of cardiomyopathy. We anticipate that this report will help shape the future research priorities in this set of diseases to achieve earlier diagnosis, improved clinical outcomes, and better quality of life for these children and their families.
    Type of Medium: Online Resource
    ISSN: 0009-7322 , 1524-4539
    URL: Article
    DOI: 10.1161/CIR.0000000000000682
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2019
    detail.hit.zdb_id: 1466401-X
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  • 3
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    Abstract 14979: Endostatin as a Predictor of Severity and Survival in Pediatric Congenital Heart Disease Associated Pulmonary Hypertension
    Ovid Technologies (Wolters Kluwer Health) ; 2020
    In:  Circulation Vol. 142, No. Suppl_3 ( 2020-11-17)
    Details
    In: Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 142, No. Suppl_3 ( 2020-11-17)
    Abstract: Introduction: Pediatric pulmonary arterial hypertension (PAH) is a multifactorial pulmonary vascular disease with high mortality. Endostatin (ES), an angiogenic inhibitor, is associated with disease severity and mortality in adults with PAH and poor lung growth in children. Hypothesis: Increased ES is associated with worse disease severity and outcomes in pediatric PAH. Methods: Serum ES levels were measured in two cohorts of pediatric PAH (IPAH, FPAH and APAH) patients; the cross-sectional CCHMC PAH Biobank (PAHB, N=175) and a longitudinal cohort from Children’s Hospital of Colorado (CHC, N=61). Outcomes included medical therapy, functional and hemodynamic measures, and survival (death, transplant, palliative shunt). Adjusted logistic and linear regressions and Kaplan-Meier analysis were used to assess the relationship between ES and clinical outcomes. Results: In both cohorts, ES was significantly higher in PAH associated with congenital heart disease (APAH-CHD, PAHB n=70, p=0.002; CHC n=29, p=0.007) and was highest in those with a ventricular shunt (n=24, p=0.001). In APAH-CHD, ES was associated with a decreased 6MWD (-108m, -187- -30, p=0.01) and increased mean right atrial pressure (mRAP 1.8mmHg, 0.3-3.3, p=0.02). Longitudinally, in the APAH-CHD subgroup when adjusted for age, sex, and multiple time points, higher ES was associated with increased PVRi and mPAP (PVRi 2.5WU*m 2 , 0.7-4.3, p=0.007; mPAP 10mmHg, 4.5-15, p 〈 0.001). Kaplan-Meier analysis (Figure 1) demonstrated that ES was associated with worse outcomes in both cohorts, with an adjusted Cox proportional hazard ratio of 4.3 (1.13-16, p=0.03) in the PAHB. Conclusions: ES was associated with worse functional measures, pulmonary vascular hemodynamics, and survival in pediatric APAH-CHD. These observations suggest that serum ES could act as a pulmonary vascular specific biomarker to identify those who are at increased risk of developing PAH and predict poor outcomes in APAH-CHD.
    Type of Medium: Online Resource
    ISSN: 0009-7322 , 1524-4539
    URL: Article
    DOI: 10.1161/circ.142.suppl_3.14979
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2020
    detail.hit.zdb_id: 1466401-X
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  • 4
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    Fatty Acid Metabolic Defects and Right Ventricular Lipotoxicity in Human Pulmonary Arterial Hypertension
    Ovid Technologies (Wolters Kluwer Health) ; 2016
    In:  Circulation Vol. 133, No. 20 ( 2016-05-17), p. 1936-1944
    Details
    In: Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 133, No. 20 ( 2016-05-17), p. 1936-1944
    Abstract: The mechanisms of right ventricular (RV) failure in pulmonary arterial hypertension (PAH) are poorly understood. Abnormalities in fatty acid (FA) metabolism have been described in experimental models of PAH, but systemic and myocardial FA metabolism has not been studied in human PAH. Methods and Results— We used human blood, RV tissue, and noninvasive imaging to characterize multiple steps in the FA metabolic pathway in PAH subjects and controls. Circulating free FAs and long-chain acylcarnitines were elevated in PAH patients versus controls. Human RV long-chain FAs were increased and long-chain acylcarnitines were markedly reduced in PAH versus controls. With the use of proton magnetic resonance spectroscopy, in vivo myocardial triglyceride content was elevated in human PAH versus controls (1.4±1.3% triglyceride versus 0.22±0.11% triglyceride, P =0.02). Ceramide, a mediator of lipotoxicity, was increased in PAH RVs versus controls. Using an animal model of heritable PAH, we demonstrated reduced FA oxidation via failure of palmitoylcarnitine to stimulate oxygen consumption in the PAH RV. Conclusions— Abnormalities in FA metabolism can be detected in the blood and myocardium in human PAH and are associated with in vivo cardiac steatosis and lipotoxicity. Murine data suggest that lipotoxicity may arise from reduction in FA oxidation.
    Type of Medium: Online Resource
    ISSN: 0009-7322 , 1524-4539
    URL: Article
    DOI: 10.1161/CIRCULATIONAHA.115.019351
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2016
    detail.hit.zdb_id: 1466401-X
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  • 5
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    Exome Sequencing in Children With Pulmonary Arterial Hypertension Demonstrates Differences Compared With Adults
    Ovid Technologies (Wolters Kluwer Health) ; 2018
    In:  Circulation: Genomic and Precision Medicine Vol. 11, No. 4 ( 2018-04)
    Details
    In: Circulation: Genomic and Precision Medicine, Ovid Technologies (Wolters Kluwer Health), Vol. 11, No. 4 ( 2018-04)
    Abstract: Pulmonary arterial hypertension (PAH) is a rare disease characterized by pulmonary arteriole remodeling, elevated arterial pressure and resistance, and subsequent heart failure. Compared with adult-onset disease, pediatric-onset PAH is more heterogeneous and often associated with worse prognosis. Although BMPR2 mutations underlie ≈70% of adult familial PAH (FPAH) cases, the genetic basis of PAH in children is less understood. Methods: We performed genetic analysis of 155 pediatric- and 257 adult-onset PAH patients, including both FPAH and sporadic, idiopathic PAH (IPAH). After screening for 2 common PAH risk genes, mutation-negative FPAH and all IPAH cases were evaluated by exome sequencing. RESULTS: We observed similar frequencies of rare, deleterious BMPR2 mutations in pediatric- and adult-onset patients: ≈55% in FPAH and 10% in IPAH patients in both age groups. However, there was significant enrichment of TBX4 mutations in pediatric- compared with adult-onset patients (IPAH: 10/130 pediatric versus 0/178 adult-onset), and TBX4 carriers had younger mean age-of-onset compared with BMPR2 carriers. Mutations in other known PAH risk genes were infrequent in both age groups. Notably, among pediatric IPAH patients without mutations in known risk genes, exome sequencing revealed a 2-fold enrichment of de novo likely gene-damaging and predicted deleterious missense variants. Conclusions: Mutations in known PAH risk genes accounted for ≈70% to 80% of FPAH in both age groups, 21% of pediatric-onset IPAH, and 11% of adult-onset IPAH. Rare, predicted deleterious variants in TBX4 are enriched in pediatric patients and de novo variants in novel genes may explain ≈19% of pediatric-onset IPAH cases.
    Type of Medium: Online Resource
    ISSN: 2574-8300
    URL: Article
    DOI: 10.1161/CIRCGEN.117.001887
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2018
    detail.hit.zdb_id: 2927603-2
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  • 6
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    Pharmacokinetics of Oral Treprostinil in Children With Pulmonary Arterial Hypertension
    Ovid Technologies (Wolters Kluwer Health) ; 2020
    In:  Journal of Cardiovascular Pharmacology Vol. 76, No. 1 ( 2020-07), p. 94-100
    Details
    In: Journal of Cardiovascular Pharmacology, Ovid Technologies (Wolters Kluwer Health), Vol. 76, No. 1 ( 2020-07), p. 94-100
    Abstract: As part of a clinical trial, this study examined the pharmacokinetics (PK) of oral treprostinil (TRE) in children with pulmonary arterial hypertension. The trial consisted of the following 3 cohorts: transition from parenteral (cohort 1) or inhaled (cohort 2) TRE, or de novo addition (cohort 3). Oral TRE was dosed 3 times daily. PK samples were obtained before an oral TRE dose, and at 2, 4, 6, and 8 hours thereafter. The PK parameters were calculated using noncompartmental analysis. Thirty-two children (n = 10 in cohorts 1 and 2, n = 12 in cohort 3) were enrolled; the median age was 12 years (range 7–17 years), and the median weight was 42.2 kg (range 19.3–78 kg). The median oral TRE dose for all subjects was 3.8 mg (5.9, 3.5, and 4.0 mg for cohorts 1, 2, and 3, respectively). The TRE concentration versus time profile demonstrated a peak concentration at a median of 3.8 hours with wide variability. In cohort 1, oral dosing led to higher peak (5.9 ng/mL) and lower trough (1 ng/mL) concentrations than parenteral (peak 5.4 ng/mL and trough 4.2 ng/mL), but a lower mean concentration (3.61 vs. 4.46 ng/mL), likely due to variable metabolism and noncomparable dosing. Both the area under the curve and average concentration were linearly correlated with oral TRE dose and dose normalized to body weight, but not with weight or age alone. In pediatric patients, an increased oral TRE dose or dose frequency may be required to minimize PK variability and achieve greater correlation with parenteral dosing.
    Type of Medium: Online Resource
    ISSN: 0160-2446
    URL: Article
    DOI: 10.1097/FJC.0000000000000842
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2020
    detail.hit.zdb_id: 2049700-3
    SSG: 15,3
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  • 7
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    Abstract 11199: Insulin-Like Growth Factor Binding Protein-4 is Associated with Pulmonary Arterial Hypertension Severity and Survival
    Ovid Technologies (Wolters Kluwer Health) ; 2021
    In:  Circulation Vol. 144, No. Suppl_1 ( 2021-11-16)
    Details
    In: Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 144, No. Suppl_1 ( 2021-11-16)
    Abstract: Introduction: Pulmonary arterial hypertension (PAH) results in progressive elevation of pulmonary vascular resistance and right heart failure. Insulin like growth factor binding proteins (IGFBPs) are a family of growth factor modifiers. As increased IGFBP4 expression is associated with vascular proliferation in lung cancer, it may also be associated with PAH severity. Hypothesis: Elevated IGFBP4 is associated with worse disease severity and survival in PAH. Methods: Using enzyme-linked immunosorbent assays (ELISA), we evaluated serum IGFBP4 in a multicenter PAH cohort, the NHLBI PAHBiobank (N=2571), and healthy controls (N=125). Hemodynamic and functional measures were used to assess IGFBP4’s association to PAH severity and survival. Spearman’s rank correlation test and Kruskal Wallis test were used for correlations. IGFBP4 was dichotomized at the median and analyzed by Kaplan-Meier survival and Cox proportional Hazard regression. Results: Serum IGFBP4 levels were significantly elevated (p 〈 0.0001) compared to controls. After adjustment for age and sex, IGFBP4 above mean was associated with a 40 meter shorter six minute walk distance (95%CI, -55 to -25, p= 〈 0.001). In the IPAH subtype only, higher IGFBP4 was associated with higher mean right atrial pressures (2 mmHg; 95%CI, 1.2 to 2.9, p= 〈 0.001), mean pulmonary arterial pressures (2.0 mmHg; 95%CI, 0.09 to 4.0, p=0.041) and pulmonary capillary wedge pressures (0.75mmHg; 95%CI, 0.18 to 1.3, p=0.010). Cox multivariable analysis demonstrated higher serum IGFBP4 as an independent predictor of survival in the overall PAHB cohort (See Figure 1; HR, 3.6; 95% CI, 2.6-5.0), with worse outcomes for CHD-APAH (HR, 9.9; CI, 2.2-45) and IPAH (HR, 5.3; 95% CI, 2.9-9.7). Conclusions: Higher circulating IGFBP4 levels are significantly associated with worse PAH severity and shorter survival. Dysregulation of IGF metabolism/growth axis could play a significant role in PAH cardio-pulmonary pathobiology.
    Type of Medium: Online Resource
    ISSN: 0009-7322 , 1524-4539
    URL: Article
    DOI: 10.1161/circ.144.suppl_1.11199
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2021
    detail.hit.zdb_id: 1466401-X
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  • 8
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    Angiostatic Peptide, Endostatin, Predicts Severity in Pediatric Congenital Heart Disease–Associated Pulmonary Hypertension
    Ovid Technologies (Wolters Kluwer Health) ; 2021
    In:  Journal of the American Heart Association Vol. 10, No. 20 ( 2021-10-19)
    Details
    In: Journal of the American Heart Association, Ovid Technologies (Wolters Kluwer Health), Vol. 10, No. 20 ( 2021-10-19)
    Abstract: Endostatin, an angiogenic inhibitor, is associated with worse pulmonary arterial hypertension (PAH) outcomes in adults and poor lung growth in children. This study sought to assess whether endostatin is associated with disease severity and outcomes in pediatric PAH. Methods and Results Serum endostatin was measured in cross‐sectional (N=160) and longitudinal cohorts (N=64) of pediatric subjects with PAH, healthy pediatric controls and pediatric controls with congenital heart disease (CHD) (N=54, N=15), and adults with CHD associated PAH (APAH‐CHD, N=185). Outcomes, assessed by regression and Kaplan‐Meier analysis, included hemodynamics, change in endostatin over time, and transplant‐free survival. Endostatin secretion was evaluated in pulmonary artery endothelial and smooth muscle cells. Endostatin was higher in those with PAH compared with healthy controls and controls with CHD and was highest in those with APAH‐CHD. In APAH‐CHD, endostatin was associated with a shorter 6‐minute walk distance and increased mean right atrial pressure. Over time, endostatin was associated with higher pulmonary artery pressure and pulmonary vascular resistance index, right ventricular dilation, and dysfunction. Endostatin decreased with improved hemodynamics over time. Endostatin was associated with worse transplant‐free survival. Addition of endostatin to an NT‐proBNP (N‐terminal pro‐B‐type natriuretic peptide) based survival analysis improved risk stratification, reclassifying subjects with adverse outcomes. Endostatin was secreted primarily by pulmonary artery endothelial cells. Conclusions Endostatin is associated with disease severity, disease improvement, and worse survival in APAH‐CHD. Endostatin with NT‐proBNP improves risk stratification, better predicting adverse outcomes. The association of elevated endostatin with shunt lesions suggests that endostatin could be driven by both pulmonary artery flow and pressure. Endostatin could be studied as a noninvasive prognostic marker, particularly in APAH‐CHD.
    Type of Medium: Online Resource
    ISSN: 2047-9980
    URL: Article
    DOI: 10.1161/JAHA.120.021409
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2021
    detail.hit.zdb_id: 2653953-6
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  • 9
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    Learning a Comorbidity-Driven Taxonomy of Pediatric Pulmonary Hypertension
    Ovid Technologies (Wolters Kluwer Health) ; 2017
    In:  Circulation Research Vol. 121, No. 4 ( 2017-08-04), p. 341-353
    Details
    In: Circulation Research, Ovid Technologies (Wolters Kluwer Health), Vol. 121, No. 4 ( 2017-08-04), p. 341-353
    Abstract: Pediatric pulmonary hypertension (PH) is a heterogeneous condition with varying natural history and therapeutic response. Precise classification of PH subtypes is, therefore, crucial for individualizing care. However, gaps remain in our understanding of the spectrum of PH in children. Objective: We seek to study the manifestations of PH in children and to assess the feasibility of applying a network-based approach to discern disease subtypes from comorbidity data recorded in longitudinal data sets. Methods and Results: A retrospective cohort study comprising 6 943 263 children ( 〈 18 years of age) enrolled in a commercial health insurance plan in the United States, between January 2010 and May 2013. A total of 1583 (0.02%) children met the criteria for PH. We identified comorbidities significantly associated with PH compared with the general population of children without PH. A Bayesian comorbidity network was constructed to model the interdependencies of these comorbidities, and network-clustering analysis was applied to derive disease subtypes comprising subgraphs of highly connected comorbid conditions. A total of 186 comorbidities were found to be significantly associated with PH. Network analysis of comorbidity patterns captured most of the major PH subtypes with known pathological basis defined by the World Health Organization and Panama classifications. The analysis further identified many subtypes documented in only a few case studies, including rare subtypes associated with several well-described genetic syndromes. Conclusions: Application of network science to model comorbidity patterns recorded in longitudinal data sets can facilitate the discovery of disease subtypes. Our analysis relearned established subtypes, thus validating the approach, and identified rare subtypes that are difficult to discern through clinical observations, providing impetus for deeper investigation of the disease subtypes that will enrich current disease classifications.
    Type of Medium: Online Resource
    ISSN: 0009-7330 , 1524-4571
    URL: Article
    DOI: 10.1161/CIRCRESAHA.117.310804
    RVK:
    XA 10000
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2017
    detail.hit.zdb_id: 1467838-X
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  • 10
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    Letter by Mosley Regarding Article, “Iron Homeostasis and Pulmonary Hypertension: Iron Deficiency Leads to Pulmonary Vascular Remodeling in the Rat”
    Ovid Technologies (Wolters Kluwer Health) ; 2015
    In:  Circulation Research Vol. 117, No. 6 ( 2015-08-28)
    Details
    In: Circulation Research, Ovid Technologies (Wolters Kluwer Health), Vol. 117, No. 6 ( 2015-08-28)
    Type of Medium: Online Resource
    ISSN: 0009-7330 , 1524-4571
    URL: Article
    DOI: 10.1161/CIRCRESAHA.115.306867
    RVK:
    XA 10000
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2015
    detail.hit.zdb_id: 1467838-X
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