Objective-Experimental studies suggest that adipose inflammation is etiologically linked to obesity-induced systemic disease. Our goal was to characterize the state of inflammation in human fat in relation to vascular function and metabolic parameters in obese individuals. Methods and Results-We collected subcutaneous abdominal fat in 77 obese subjects (BMI Ն30 kg/m 2 ) and quantified adipose macrophage population using targeted immunohistochemistry. Brachial artery vasodilator function was examined using high-resolution vascular ultrasound. In 50 subjects, an inflamed adipose phenotype characterized by tissue macrophage accumulation in crown-like structures was associated with systemic hyperinsulinemia and insulin resistance (HOMA-IR 5.5Ϯ4.5 versus 2.6Ϯ1.9, Pϭ0.002) and impaired endothelium-dependent flow-mediated vasodilation (8.5Ϯ4.4% versus 10.8Ϯ3.8%, PϽ0.05), as compared to subjects with quiescent noninflamed adipose architecture (nϭ27). Macrophage retention in fat was linked to upregulated tissue CD68 and tumor necrosis factor (TNF)-␣ mRNA expression in addition to increased plasma hs-CRP. Conclusions-In a cohort of obese subjects, we demonstrate that proinflammatory changes in adipose tissue are associated with systemic arterial dysfunction and insulin resistance. These findings suggest that adipose inflammation may be linked to vascular injury and increased cardiovascular risk in obese subjects. (Arterioscler Thromb Vasc Biol. 2008;28:1654-1659)Key Words: obesity Ⅲ endothelium Ⅲ inflammation Ⅲ insulin Ⅲ vasculature O besity represents a disease state characterized by chronic subclinical inflammation linked to increased risk of type-2 diabetes and atherosclerosis. 1,2 Although the stimulus or source for persistent immune activation remains unclear, fat tissue is increasingly being recognized as an important hotbed of metabolic activity and a significant source of proatherogenic and proinflammatory adipocytokines that orchestrate metabolic and vascular dysfunction. 3,4 Animal studies suggest that adipose tissue macrophage (ATM) activity is functionally intertwined with systemic disease mechanisms. [5][6][7] The pathogenic link is supported by pharmacogenetic studies demonstrating that attenuation of ATM influx alters cytokine production and improves insulin sensitivity. 8,9 From a clinical perspective, inflammatory changes in fat have not been commonly investigated in human disease nor examined in the context of functional cardiovascular abnormalities.Inflammatory mechanisms are critical to all stages of cardiovascular disease progression and play a causal role in vascular endothelial dysfunction that represents a crucial early event in atherosclerosis and subsequent coronary heart disease (CHD) events. 10,11 These mechanisms are, in part, supported by local and systemic release of inflammatory cytokines that mediate activation of neutrophils, monocytes, and T-cells, promote lipid-laden foam cell accumulation, weaken atherosclerotic plaque stability, and impair nitric oxide (NO)-mediated endothelium-depend...
Obesity is associated with altered arterial homeostasis and endothelial dysfunction. Mechanisms of disease are related to a complex interplay of metabolic and inflammatory factors that coordinately improve along with arterial function in response to weight loss interventions.
Navigating the balance of autonomy, independence, and self-discovery are some of the chief hallmarks of adolescence. For solid organ transplantation (SOT) recipients, adolescence and young adulthood (AYA) are fraught with added complexities such as maintaining the complex medication regimens necessary to maintain the patient and allograft's health. This time also brings with it physiologic and psychosocial changes which require special attention. Many SOT programs seek to meet these needs by
Culturally contextualized interventions are needed to initiate and facilitate the risk-reduction efforts of HIV-infected rural persons.
Increased blood pressure variability (BPV) is correlated with adverse cardiovascular (CV) events in adults. However, there has been limited research on its effect in the pediatric population. Additionally, BPV differences between primary and secondary hypertension (HTN) are not known. Children with primary and secondary HTN underwent 24-hour ambulatory blood pressure monitoring and echocardiography studies. BPV measures of standard deviation (SD), average real variability (ARV), and range were calculated for the 24-hour, daytime, and nighttime periods. Seventy-four patients (median age, 13.5 years; 74% boys) were examined, 40 of whom had primary HTN. Body mass index z score and age were independent predictors of systolic ARV (R 2 =0.14) and SD (R 2 =0.39). There were no statistically significant differences in overall or wake period BPV measures between secondary or primary HTN groups, but sleep period diastolic SD was significantly greater in the secondary HTN group (9.26AE3.8 vs 7.1AE2.8, P=.039). On multiple regression analysis, secondary HTN was associated with increased sleep period diastolic SD (P=.025). No metrics of BPV in the overall, wake, and sleep periods were found to be significantly associated with left ventricular hypertrophy (LVH). The results of this study do not show a strong relationship between overall or wake BPV with primary vs secondary HTN, but the association of secondary HTN with sleep period diastolic BPV deserves further exploration. Contrary to expectation, the findings of this study failed to indicate a relationship between BPV and LVH for all patients as well for primary hypertensive and secondary hypertensive patients.
IntroductionQualitative research reveals significant caregiver impact resulting from managing children requiring chronic dialysis but offers few quantitative measures of their lived experiences.Materials and MethodsThis cross-sectional study included 25 caregivers of children on chronic peritoneal dialysis (PD) and hemodialysis (HD) enrolled from 2018 to 2019 at a large pediatric dialysis program in the U.S.Patient Reported Outcomes Measures Information System (PROMIS) measures and free text commentary were collected and analyzed to evaluate the self-reported impact and wellbeing of these caregivers.ResultsAmong all dialysis modalities, caregivers' positive affect (43.4 ± 10) and general life satisfaction (45.1 ± 11.5) were significantly lower than the general adult population. Compared with HD caregivers, PD caregivers demonstrated significantly more fatigue and sleep disturbance and less positive affect and life satisfaction. Amongst HD caregivers, sleep disturbance, positive affect, and meaning/purpose differed significantly from the general population. Analyses of text commentary revealed that caregivers also expressed the feelings of loss, importance of knowing the impact of dialysis prior to initiation, need for a support group, and value of home nursing.ConclusionsCaregivers of children on chronic dialysis had significantly poorer self-rated health and wellbeing compared with the general adult population. This may be due in part to their feelings of social isolation. Our findings highlight opportunities to improve caregivers' lived experiences.
With the opioid epidemic and expansion of “IR” classification, 25% of deceased donors are categorized PHS‐IR. Studies have assessed utilization of PHS‐IR organs among adults, but little is known about pediatric recipients. This retrospective cohort study from 2004‐2016 (IR period) aimed to: (a) assess IR kidney utilization patterns between adults and children; (b) identify recipient factors associated with transplant from IR donors among pediatric kidney recipients; and (c) determine geography's role in IR kidney utilization for children. The proportion of pediatric recipients receiving IR kidneys was significantly lower than adults (P < 0.001), even when stratified by donor mechanism of death (non‐overdose/overdose) and era. In mixed effects models accounting for clustering within centers and regions, older recipient age, later era (post‐PHS‐IR expansion), and blood type were associated with significantly higher odds of receiving an IR kidney (17 years era 5: OR 5.16 [CI 2.05‐13.1] P < 0.001; 18‐21 years era 5: OR 2.72 [CI 1.05‐7.06] P = 0.04; blood type O: OR 1.32 [CI 1.06‐1.64] P = 0.013). The median odds ratio for center within region was 1.77 indicating that when comparing two patients in a region, the odds of receiving an IR kidney were 77% higher for a patient from a center with higher likelihood of receiving an IR kidney. Utilization of PHS‐IR kidneys is significantly lower among pediatric recipients versus adult counterparts. More work is needed to understand the reasons for these differences in children in order to continue their access to this life‐prolonging therapy.
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