Health-related quality of life of children with first onset steroid-sensitive nephrotic syndrome

This study assessed HRQoL and emotional and behavioral difficulties (EBD) and associated variables in children with first onset SSNS. While relapsing steroid-sensitive nephrotic syndrome (SSNS) in children is associated with lower health-related quality of life (HRQoL), little is known about first onset. Four weeks after onset, children (2–16 years) and/or their parents who participated in a randomized placebo-controlled trial, completed the Pediatric Quality of Life Inventory 4.0 (PedsQL) and Strengths and Difficulties Questionnaire (SDQ) to measure HRQoL and EBD, respectively. Total and subscale scores and the proportion of children with impaired HRQoL (&gt; 1 SD below the mean of the reference group) or SDQ clinical scores (&lt; 10th and &gt; 90th percentile) were compared to the Dutch general population (reference group). Regression analyses were used to identify associated variables. Compared to the reference group, children 8–18 years reported significantly lower total HRQoL, and physical and emotional functioning. A large proportion (&gt; 45%) of these children had impaired HRQoL. There were no differences in HRQoL between children 2–7 years and the reference group, except for higher scores on social functioning (5–7 years). Similar proportions of SSNS and reference children scored within the clinical range of SDQ subscales. Age, sex, and steroid side-effects were negatively associated with HRQol and/or EBD. Conclusion: This study showed that HRQoL and EBD are affected in children of different ages with first onset SSNS. This calls for more awareness from healthcare providers and routinely monitoring of HRQoL and EBD in daily clinical care to prevent worsening of symptoms. Clinical trial registry: Netherlands Trial Register (https://trialsearch.who.int/ ; NTR7013), date of registration: 02 June 2018. What is Known: • Health-related quality of life (HRQoL) is lower and emotional and behavioral difficulties (EBD) is more affected in children with frequently-relapsing and steroid-dependent nephrotic syndrome. What is New: • HRQoL and EBD are affected in children with first onset steroid-sensitive nephrotic syndrome compared to a reference group of the Dutch general population. • To what extent HRQoL and EBD are affected depends on the age of the patient.</p

Increased platelet reactivity is associated with circulating platelet-monocyte complexes and macrophages in human atherosclerotic plaques

Objective: Platelet reactivity, platelet binding to monocytes and monocyte infiltration play a detrimental role in atherosclerotic plaque progression. We investigated whether platelet reactivity was associated with levels of circulating platelet-monocyte complexes (PMCs) and macrophages in human atherosclerotic carotid plaques. Methods: Platelet reactivity was determined by measuring platelet P-selectin expression after platelet stimulation with increasing concentrations of adenosine diphosphate (ADP), in two independent cohorts: the Circulating Cells cohort (n = 244) and the Athero-Express cohort (n = 91). Levels of PMCs were assessed by flow cytometry in blood samples of patients who were scheduled for percutaneous coronary intervention (Circulating Cells cohort). Monocyte infiltration was semi-quantitatively determined by histological examination of atherosclerotic carotid plaques collected during carotid endarterectomy (Athero-Express cohort). Results: We found increased platelet reactivity in patients with high PMCs as compared to patients with low PMCs (median (interquartile range): 4153 (1585-11267) area under the curve (AUC) vs. 9633 (3580-21565) AUC, P<0.001). Also, we observed increased pl

A fibronectin-fibrinogen-tropoelastin coating reduces smooth muscle cell growth but improves endothelial cell function

Reendothelialization of the stent surface after percutaneous coronary intervention (PCI) is known to be an important determinant of clinical outcome. We compared the effects of biological stent coatings, fibronectin, fibrinogen and tropoelastin, on human umbilical vein endothelial cell (HUVEC) and vascular smooth muscle cell (VSMC) characteristics. Umbilical cord arterial segments were cultured on coated surfaces and VSMC outgrowth (indicating proliferation and migration) was measured after 12 days. mRNA was isolated from HUVEC and VSMC cultured on these coatings and gene expression was profiled by QPCR. Procoagulant properties of HUVEC were determined by an indirect chromogenic assay which detects tissue factor activity. The varying stent coatings influence VSMC outgrowth: 31.2 ± 4.0 mm(2) on fibronectin, 1.6 ± 0.3 mm(2) on tropoelastin and 8.1 ± 1.5 mm(2) on a mixture of fibronectin/fibrinogen/tropoelastin, although HUVEC migration remains unaffected. Culturing HUVEC on tropoelastin induces increased expression of VCAM-1 (13.1 ± 4.4 pg/ml), ICAM-1 (5.1 ± 1.3 pg/ml) and IL-8 (11.6 ± 3.1 pg/ml) compared to fibronectin (0.7 ± 0.2, 0.8 ± 0.2, 2.3 ± 0.5 pg/ml, respectively), although expression levels on fibronectin/fibrinogen/tropoelastin remain unaltered. No significant differences in VCAM-1, ICAM-1 and IL-8 mRNA expression are found in VSMC. Finally, HUVEC cultured on tropoelastin display a fivefold increased tissue factor activity (511.6 ± 26.7%), compared to cells cultured on fibronectin (100 ± 3.9%) or fibronectin/fibrinogen/tropoelastin (76.3 ± 25.0%). These results indicate that tropoelastin inhibits VSMC migration but leads to increased inflammatory and procoagulant markers on endothelial cells. Fibronectin/fibrinogen/tropoelastin inhibits VSMCs while compensating the inflammatory and procoagulant effects. These data suggest that coating a mixture of fibronectin/fibrinogen/tropoelastin on a stent may promote reendothelialization, while keeping unfavourable processes such as restenosis and procoagulant activity limited.status: publishe

Distress in parents of children with first-onset steroid-sensitive nephrotic syndrome

Background Steroid-sensitive nephrotic syndrome (SSNS) is associated with a relapsing-remitting course that can be stressful for parents. As little is known of parental distress at the first onset of SSNS, this study aims to describe parental distress and everyday problems in mothers and fathers of a child with newly diagnosed SSNS participating in a randomized controlled trial of levamisole added to corticosteroids. Methods To assess distress, the Distress Thermometer for Parents (DT-P) was used, which includes questions on distress (thermometer score 0-10, >= 4 "clinical distress") and presence of everyday problems in six domains: practical, social, emotional, physical, cognitive, and parenting. The DT-P was completed 4 weeks after the onset of SSNS. Total sum and individual items of everyday problems were compared with reference data from mothers and fathers of the Dutch general population. Results There was no difference in clinically elevated parental distress between SSNS mothers (n = 37) and fathers (n = 25) and reference parents. Compared to reference fathers, fathers of a child with SSNS scored significantly higher on emotional problems (P = 0.030), while mothers experienced more parenting problems (P = 0.002). Regression analyses showed that lower parental age and having a girl with SSNS were significantly associated with more practical problems and higher distress thermometer scores, respectively. Conclusions Four weeks after onset, SSNS mothers and fathers experience equal distress as reference parents. However, both parents endorsed significantly more everyday problems. Therefore, monitoring parental distress, even in the first weeks of the disease, could contribute to timely interventions and prevent worsening of problems. Clinical trial registry Dutch Trial Register (https://onderzoekmetmensen.nl/en/trial/27331)

Increased Platelet Reactivity Is Associated with Circulating Platelet-Monocyte Complexes and Macrophages in Human Atherosclerotic Plaques

OBJECTIVE: Platelet reactivity, platelet binding to monocytes and monocyte infiltration play a detrimental role in atherosclerotic plaque progression. We investigated whether platelet reactivity was associated with levels of circulating platelet-monocyte complexes (PMCs) and macrophages in human atherosclerotic carotid plaques. METHODS: Platelet reactivity was determined by measuring platelet P-selectin expression after platelet stimulation with increasing concentrations of adenosine diphosphate (ADP), in two independent cohorts: the Circulating Cells cohort (n = 244) and the Athero-Express cohort (n = 91). Levels of PMCs were assessed by flow cytometry in blood samples of patients who were scheduled for percutaneous coronary intervention (Circulating Cells cohort). Monocyte infiltration was semi-quantitatively determined by histological examination of atherosclerotic carotid plaques collected during carotid endarterectomy (Athero-Express cohort). RESULTS: We found increased platelet reactivity in patients with high PMCs as compared to patients with low PMCs (median (interquartile range): 4153 (1585-11267) area under the curve (AUC) vs. 9633 (3580-21565) AUC, P<0.001). Also, we observed increased platelet reactivity in patients with high macrophage levels in atherosclerotic plaques as compared to patients with low macrophage levels in atherosclerotic plaques (mean ± SD; 8969 ± 3485 AUC vs. 7020 ± 3442 AUC, P = 0.02). All associations remained significant after adjustment for age, sex and use of drugs against platelet activation. CONCLUSION: Platelet reactivity towards ADP is associated with levels of PMCs and macrophages in human atherosclerotic carotid plaques.status: publishe

Increased Platelet Reactivity Is Associated with Circulating Platelet-Monocyte Complexes and Macrophages in Human Atherosclerotic Plaques

Objective: Platelet reactivity, platelet binding to monocytes and monocyte infiltration play a detrimental role in atherosclerotic plaque progression. We investigated whether platelet reactivity was associated with levels of circulating platelet-monocyte complexes (PMCs) and macrophages in human atherosclerotic carotid plaques. Methods: Platelet reactivity was determined by measuring platelet P-selectin expression after platelet stimulation with increasing concentrations of adenosine diphosphate (ADP), in two independent cohorts: the Circulating Cells cohort (n = 244) and the Athero-Express cohort (n = 91). Levels of PMCs were assessed by flow cytometry in blood samples of patients who were scheduled for percutaneous coronary intervention (Circulating Cells cohort). Monocyte infiltration was semi-quantitatively determined by histological examination of atherosclerotic carotid plaques collected during carotid endarterectomy (Athero-Express cohort). Results: We found increased platelet reactivity in patients with high PMCs as compared to patients with low PMCs (median (interquartile range): 4153 (1585-11267) area under the curve (AUC) vs. 9633 (3580-21565) AUC,

Platelet reactivity related to macrophage levels.

<p>Comparison of the AUC after ADP stimulation between low (n = 67) versus high macrophage levels in atherosclerotic carotid plaques (n = 24). Grey bars represent means with standard deviations. MFI = mean fluorescence intensity, AUC = area under curve, ADP = adenosine diphosphate.</p

Histology of macrophage levels in atherosclerotic carotid plaques.

<p>Macrophage staining (brown), nucleus staining with haematoxylin (blue). (<b>a</b>) Low macrophage levels (40× magnification). (<b>b</b>) Higher magnification of the indicated area in (a) (100× magnification). (<b>c</b>) High macrophage levels (40× magnification). (<b>d</b>) Higher magnification of the indicated area in (c) (100× magnification).</p

Conversion of dose-response curve into area under the curve.

<p>In order to compare total platelet reactivity between patients, we derived the area under the curve from each dose response curve. MFI = mean fluorescence intensity, AUC = area under curve, ADP = adenosine diphosphate.</p

Baseline characteristics.

<p>Continuous values are expressed as mean ± standard deviation (unless specified otherwise). Categorical values are expressed as number of total (percentage).</p><p>CG = Cockroft-Gault, CEA = carotid endarterectomy, IQR = interquartile range.</p