Background: Obesity-associated chronic low-grade inflammation leads to dysregulation of central lipid and glucose metabolism pathways leading to metabolic disorders. MicroRNAs (miRNAs) are known to control regulators of metabolic homeostasis. We aimed to assess the relationship of circulating miRNAs with inflammatory modulators and metabolic disorders in pediatric obesity. Methods: From a pediatric cohort with severe obesity (n = 109), clinically thoroughly characterized including diverse routine blood parameters, oral glucose tolerance test, and liver MRI, a panel of 16 circulating miRNAs was quantified using qRT-PCR. Additionally, markers of inflammation TNFα, IL1 receptor antagonist, procalcitonin, CRP, and IL-6 were measured. Results: Markers of obesity-associated inflammation, TNFα, IL-1Ra, and procalcitonin, all significantly correlated with concentrations of miRNAs 122 and 192. Concentrations of these miRNAs negatively correlated with serum adiponectin and were among those strongly linked to parameters of dyslipidemia and liver function. Moreover, miRNA122 concentrations correlated with HOMA-IR. Several miRNA levels including miRNAs 34a, 93, 122, and 192 were statistically significantly differing between individuals with prediabetes, impaired glucose tolerance, metabolic syndrome, or nonalcoholic fatty liver disease compared to the respective controls. Additionally, miRNA 192 was significantly elevated in metabolically unhealthy obesity. Conclusions: A miRNA pattern associated with obesity-associated inflammation and comorbidities may be used to distinguish metabolically healthy from unhealthy pediatric patients with obesity. Moreover, these changes in epigenetic regulation could potentially be involved in the etiology of obesity-linked metabolic disease in children and adolescents.
Purpose: About 10% of patients with neurofibromatosis type 1 (NF‐1) develop malignant peripheral nerve sheath tumours (MPNST) mostly arising in plexiform neurofibroma (PN); 15% of MPNST arise in children and adolescents. 2‐[18F]fluoro‐2‐deoxy‐d‐glucose ([18F]FDG)‐PET (where PET is positron emission tomography) is a sensitive method in differentiating PN and MPNST in symptomatic patients with NF‐1. This study assesses the value of [18F]FDG‐PET imaging in detecting malignant transformation in symptomatic and asymptomatic children with PN.Methods: Forty‐one patients with NF‐1 and extensive PN underwent prospective [18F]FDG imaging from 2003 to 2014. Thirty‐two of the patients were asymptomatic. PET data, together with histological results and clinical course were re‐evaluated retrospectively. Maximum standardised uptake values (SUVmax) and lesion‐to‐liver ratio were assessed.Results: A total of 104 examinations were performed. Mean age at first PET was 13.5 years (2.6–22.6). Eight patients had at least one malignant lesion; four of these patients were asymptomatic. Two of four symptomatic patients died, while all patients with asymptomatic malignant lesions are alive. All malignant tumours could be identified by PET imaging in both symptomatic and asymptomatic patients. All lesions judged as benign by [18F]FDG imaging and clinical judgment were either histologically benign if removed or remained clinically silent during follow‐up. SUVmax of malignant and benign lesions overlapped, but no malignant lesion showed FDG uptake ≤3.15. Asymptomatic malignant lesions were detected with a sensitivity of 100%, a negative predictive value of 100% and a specificity of 45.1%.Conclusion: Malignant transformation of PN also occurs in asymptomatic children and adolescents. Detection of MPNST at early stages could increase the possibility of oncologically curative resections.
Malignant diseases during pregnancy are relatively rare, with an estimated incidence of 1 in 1000 pregnancies.1 Owing to an increasing delay of pregnancy to the third and fourth decades of life, cancer will occur increasingly more frequently during pregnancy. Diagnosis is reportedly often delayed during pregnancy, due to overlapping symptoms of pregnancy and malignant disease, leading to higher stages of disease at diagnosis.1