Plasma lipid profiles discriminate bacterial from viral infection in febrile children

Fever is the most common reason that children present to Emergency Departments. Clinical signs and symptoms suggestive of bacterial infection are often non-specific, and there is no definitive test for the accurate diagnosis of infection. The 'omics' approaches to identifying biomarkers from the host-response to bacterial infection are promising. In this study, lipidomic analysis was carried out with plasma samples obtained from febrile children with confirmed bacterial infection (n = 20) and confirmed viral infection (n = 20). We show for the first time that bacterial and viral infection produces distinct profile in the host lipidome. Some species of glycerophosphoinositol, sphingomyelin, lysophosphatidylcholine and cholesterol sulfate were higher in the confirmed virus infected group, while some species of fatty acids, glycerophosphocholine, glycerophosphoserine, lactosylceramide and bilirubin were lower in the confirmed virus infected group when compared with confirmed bacterial infected group. A combination of three lipids achieved an area under the receiver operating characteristic (ROC) curve of 0.911 (95% CI 0.81 to 0.98). This pilot study demonstrates the potential of metabolic biomarkers to assist clinicians in distinguishing bacterial from viral infection in febrile children, to facilitate effective clinical management and to the limit inappropriate use of antibiotics

Regional right ventricular remodeling and function in children with idiopathic pulmonary arterial hypertension vs those with pulmonary valve stenosis : Insights into mechanics of right ventricular dysfunction

BACKGROUND: Right ventricular (RV) pressure overload in the context of pulmonary stenosis (PS) has a much better prognosis than in the context of idiopathic pulmonary arterial hypertension (iPAH), which may be related to differences in global and regional RV remodeling and systolic function. We compared RV mechanics in children with PS to those with iPAH, aiming to identify mechanisms and markers of RV dysfunction. METHODS: Eighteen controls, 18 iPAH and 16 PS patients were retrospectively studied. Age, BSA, and sex distribution were comparable. Two-dimensional echocardiography, blood flow and tissue Doppler, and longitudinal RV deformation were analyzed. ANCOVA-including RV systolic pressure (RVSP) and length as covariates-was used to compare patient groups. RESULTS: RV systolic pressure was higher in iPAH vs PS (96.8±25.4 vs 75.4±18.9 mm Hg, P=.011). Compared to controls, PS patients showed mild dilation (P<.01) and decreased longitudinal deformation (P<.001) at the RV apex. Compared to both PS and controls, iPAH patients showed marked spherical RV dilation (P<.001), reduced global, RV free wall and septal longitudinal deformation (iPAH -22.07%±4.35% vs controls -28.18%±1.69%; -9.98%±4.30% vs -17.45%±2.52%; P<.001) and RV postsystolic shortening (P<.001). RV transverse shortening (radial performance) was increased in PS (31.75%±10.35%; P<.001) but reduced in iPAH (-1.62%±11.11% vs controls 12.00%±7.74%; P<.001). CONCLUSION: Children with iPAH demonstrate adverse global and regional RV remodeling and mechanics compared to those with PS. Mechanisms of RV systolic dysfunction in iPAH include decreased longitudinal deformation, decreased or absent transverse shortening, and postsystolic shortening. These markers may be useful to identify children at risk of RV failure

Left ventricular function and exercise capacity after arterial switch operation for transposition of the great arteries : a systematic review and meta-analysis

BACKGROUND: The arterial switch operation for transposition of the great arteries was initially believed to be an anatomical correction. Recent evidence shows reduced exercise capacity and left ventricular function in varying degrees in the long term after an arterial switch operation. OBJECTIVE: To perform a meta-analysis on long-term exercise capacity and left ventricular ejection fraction after an arterial switch operation. METHODS: A literature search was performed to cover all studies on patients who had undergone a minimum of 6 years of follow-up that reported either left ventricular ejection fraction, peak oxygen uptake, peak workload, and/or peak heart rate. A meta-analysis was performed if more than three studies reported the outcome of interest. RESULTS: A total of 21 studies reported on the outcomes of interest. Oxygen uptake was consistently lower in patients who had undergone an arterial switch operation compared with healthy controls, with a pooled average peak oxygen uptake of 87.5±2.9% of predicted. The peak heart rate was also lower compared with that of controls, at 92±2% of predicted. Peak workload was significantly reduced in two studies. Pooled left ventricular ejection fraction was normal at 60.7±7.2%. CONCLUSION: Exercise capacity is reduced and left ventricular ejection fraction is preserved in the long term after an arterial switch operation for transposition of the great arteries

Adverse ventricular-ventricular interactions in right ventricular pressure load : Insights from pediatric pulmonary hypertension versus pulmonary stenosis

Right ventricular (RV) pressure overload has a vastly different clinical course in children with idiopathic pulmonary arterial hypertension (iPAH) than in children with pulmonary stenosis (PS). While RV function is well recognized as a key prognostic factor in iPAH, adverse ventricular-ventricular interactions and LV dysfunction are less well characterized and the pathophysiology is incompletely understood. We compared ventricular-ventricular interactions as hypothesized drivers of biventricular dysfunction in pediatric iPAH versus PS Eighteen iPAH, 16 PS patients and 18 age- and size-matched controls were retrospectively studied. Cardiac cycle events were measured by M-mode and Doppler echocardiography. Measurements were compared between groups using ANOVA with post hoc Dunnet's or ANCOVA including RV systolic pressure (RVSP; iPAH 96.8 ± 25.4 mmHg vs. PS 75.4 ± 18.9 mmHg; P = 0.011) as a covariate. RV-free wall thickening was prolonged in iPAH versus PS, extending beyond pulmonary valve closure (638 ± 76 msec vs. 562 ± 76 msec vs. 473 ± 59 msec controls). LV and RV isovolumetric relaxation were prolonged in iPAH (P < 0.001; LV 102.8 ± 24.1 msec vs. 63.1 ± 13.7 msec; RV 95 [61-165] vs. 28 [0-43]), associated with adverse septal kinetics; characterized by rightward displacement in early systole and leftward displacement in late RV systole (i.e., early LV diastole). Early LV diastolic filling was decreased in iPAH (73 ± 15.9 vs. PS 87.4 ± 14.4 vs. controls 95.8 ± 12.5 cm/sec; P = 0.004). Prolonged RVFW thickening, prolonged RVFW isovolumetric times, and profound septal dyskinesia are associated with interventricular mechanical discoordination and decreased early LV filling in pediatric iPAH much more than PS These adverse mechanics affect systolic and diastolic biventricular efficiency in iPAH and may form the basis for worse clinical outcomes. We used clinically derived data to study the pathophysiology of ventricular-ventricular interactions in right ventricular pressure overload, demonstrating distinct differences between pediatric pulmonary arterial hypertension (iPAH) and pulmonary stenosis (PS). Altered timing of right ventricular free wall contraction and profound septal dyskinesia are associated with interventricular mechanical discoordination and decreased early LV filling in iPAH much more than PS These adverse mechanics affect systolic and diastolic biventricular efficiency, independent of right ventricular systolic pressure

Patterns of treatment and survival among older patients with stage III non-small cell lung cancer

INTRODUCTION: Patterns of treatment and survival are largely unknown for older patients with stage III non-small cell lung cancer (NSCLC) in daily clinical practice. METHODS: All patients ≥65 years with stage III NSCLC (2009-2013) were included from the population-based Netherlands Cancer Registry. Descriptive and multivariable treatment and survival analyses were stratified for patients aged 65-74 years and ≥75 years. RESULTS: Compared to older patients (n = 3163), those aged 65-74 years (n = 3876) underwent more often surgery (21% vs 12% for stage IIIA), chemoradiotherapy (47% vs 22% for both stage IIIA and IIIB), and chemotherapy (23% vs 12% for stage IIIB), and received less radiotherapy (8% vs 22% for both stage IIIA and IIIB). One-year survival was significantly higher among patients aged 65-74 compared to those aged ≥75 (61% vs 43%, for stage IIIA and 45% vs 30% for stage IIIB; P < .01). However, stratification of treatment showed similar survival rates between age groups. Among patients aged 65-74 years, the multivariably adjusted hazard ratio (HR) of death was twice as high for patients receiving radiotherapy (HR 1.9 (95%CI 1.6-2.2) for stage IIIA and HR 2.5 (95%CI 2.1-3.0) for stage IIIB) and chemotherapy (HR 2.2 (95%CI 1.9-2.5) and HR 2.2 (95%CI 1.8-2.7), respectively) compared to chemoradiotherapy, and were slightly lower for patients aged ≥75 years receiving radiotherapy (HR 1.6 (95%CI 1.4-1.9) and HR 1.8 (95%CI 1.5-2.1), respectively) and chemotherapy (HR 2.2 (95%CI 1.8-2.7) and HR 1.8 (95%CI 1.5-2.2), respectively). Comorbidity was not significantly associated with poorer survival (p = .07). CONCLUSION: Chemoradiotherapy was more often applied among patients aged 65-74 years compared to those aged ≥75. While survival was worse for patients aged ≥75 years, differences between age groups largely disappeared after stratification for treatment. Future research should focus on predictive patient characteristics to distinguish patients within the heterogeneous older population who can benefit from curative-intent treatment

Patterns of treatment and survival among older patients with stage III non-small cell lung cancer

INTRODUCTION: Patterns of treatment and survival are largely unknown for older patients with stage III non-small cell lung cancer (NSCLC) in daily clinical practice. METHODS: All patients ≥65 years with stage III NSCLC (2009-2013) were included from the population-based Netherlands Cancer Registry. Descriptive and multivariable treatment and survival analyses were stratified for patients aged 65-74 years and ≥75 years. RESULTS: Compared to older patients (n = 3163), those aged 65-74 years (n = 3876) underwent more often surgery (21% vs 12% for stage IIIA), chemoradiotherapy (47% vs 22% for both stage IIIA and IIIB), and chemotherapy (23% vs 12% for stage IIIB), and received less radiotherapy (8% vs 22% for both stage IIIA and IIIB). One-year survival was significantly higher among patients aged 65-74 compared to those aged ≥75 (61% vs 43%, for stage IIIA and 45% vs 30% for stage IIIB; P < .01). However, stratification of treatment showed similar survival rates between age groups. Among patients aged 65-74 years, the multivariably adjusted hazard ratio (HR) of death was twice as high for patients receiving radiotherapy (HR 1.9 (95%CI 1.6-2.2) for stage IIIA and HR 2.5 (95%CI 2.1-3.0) for stage IIIB) and chemotherapy (HR 2.2 (95%CI 1.9-2.5) and HR 2.2 (95%CI 1.8-2.7), respectively) compared to chemoradiotherapy, and were slightly lower for patients aged ≥75 years receiving radiotherapy (HR 1.6 (95%CI 1.4-1.9) and HR 1.8 (95%CI 1.5-2.1), respectively) and chemotherapy (HR 2.2 (95%CI 1.8-2.7) and HR 1.8 (95%CI 1.5-2.2), respectively). Comorbidity was not significantly associated with poorer survival (p = .07). CONCLUSION: Chemoradiotherapy was more often applied among patients aged 65-74 years compared to those aged ≥75. While survival was worse for patients aged ≥75 years, differences between age groups largely disappeared after stratification for treatment. Future research should focus on predictive patient characteristics to distinguish patients within the heterogeneous older population who can benefit from curative-intent treatment

Advances in cardiac magnetic resonance imaging of congenital heart disease

Due to advances in cardiac surgery, survival of patients with congenital heart disease has increased considerably during the past decades. Many of these patients require repeated cardiovascular magnetic resonance imaging to assess cardiac anatomy and function. In the past decade, technological advances have enabled faster and more robust cardiovascular magnetic resonance with improved image quality and spatial as well as temporal resolution. This review aims to provide an overview of advances in cardiovascular magnetic resonance hardware and acquisition techniques relevant to both pediatric and adult patients with congenital heart disease and discusses the techniques used to assess function, anatomy, flow and tissue characterization