Liver Fat, Bone Marrow Adipose Tissue, and Bone Mineral Density in Children With Overweight.

CONTEXT: Hepatic steatosis is associated with decreased bone mineral density (BMD). Bone marrow fat fraction (BMFF) could play a role in this relationship in children with obesity. OBJECTIVE: The objectives of this work were (i) to examine the relationship between the lumbar spine (LS) BMFF and BMD, and (ii) to explore the mediating role of LS-BMFF on the relationship between percentage hepatic fat with LS-BMD in preadolescent children with overweight/obesity. METHODS: Hepatic fat and LS-BMFF (magnetic resonance imaging) and areal LS-BMD (LS-aBMD, dual-energy x-ray absorptiometry) were measured in 106 children (aged 10.6 ± 1.1 years, 53.8% girls) with overweight/obesity. RESULTS: LS-BMFF was inversely associated with LS-aBMD (r = -0.313; P = .001) and directly related with percentage hepatic fat (r = 0.276; P = .005). LS-BMFF was significantly greater in children with than without hepatic steatosis (P = .003; Cohen's d: 0.61; 95% CI, -0.21 to 1.0), while no significant difference was seen between children with overweight and those with obesity (P = .604; Cohen's d: 0.16; 95% CI, -0.21-0.55). Mediating analysis indicated that LS-BMFF is an important mediator (50%) in the association of hepatic fat with lower LS-aBMD (indirect effect: ß = -.076; 95% CI, -0.143 to -0.015). CONCLUSION: These findings suggest that hepatic steatosis, rather than overall excess adiposity, is associated with greater bone marrow adipose tissue in preadolescent children with overweight/obesity, which in turn, is related to lower BMD. Hepatic steatosis could be a potential biomarker of osteoporosis risk, and a therapeutic target for interventions that aim to reduce not only hepatic steatosis, but for those designed to improve bone health in such children.

Differences in specific abdominal fat depots between metabolically healthy and unhealthy children with overweight/obesity: The role of cardiorespiratory fitness.

OBJECTIVES: Fat depots localization has a critical role in the metabolic health status of adults. Nevertheless, whether that is also the case in children remains under-studied. Therefore, the aims of this study were: (i) to examine the differences between metabolically healthy (MHO) and unhealthy (MUO) overweight/obesity phenotypes on specific abdominal fat depots, and (ii) to further explore whether cardiorespiratory fitness plays a major role in the differences between metabolic phenotypes among children with overweight/obesity. METHODS: A total of 114 children with overweight/obesity (10.6 ± 1.1 years, 62 girls) were included. Children were classified as MHO (n = 68) or MUO. visceral (VAT), abdominal subcutaneous (ASAT), intermuscular abdominal (IMAAT), psoas, hepatic, pancreatic, and lumbar bone marrow adipose tissues were measured by magnetic resonance imaging. Cardiorespiratory fitness was assessed using the 20 m shuttle run test. RESULTS: MHO children had lower VAT and ASAT contents and psoas fat fraction compared to MUO children (difference = 12.4%-25.8%, all p < 0.035). MUO-unfit had more VAT and ASAT content than those MUO-fit and MHO-fit (difference = 34.8%-45.3%, all p < 0.044). MUO-unfit shows also greater IMAAT fat fraction than those MUO-fit and MHO-fit peers (difference = 16.4%-13.9% respectively, all p ≤ 0.001). In addition, MHO-unfit presented higher IMAAT fat fraction than MHO-fit (difference = 13.4%, p < 0.001). MUO-unfit presented higher psoas fat fraction than MHO-fit (difference = 29.1%, p = 0.008). CONCLUSIONS: VAT together with ASAT and psoas fat fraction, were lower in MHO than in MUO children. Further, we also observed that being fit, regardless of metabolic phenotype, has a protective role over the specific abdominal fat depots among children with overweight/obesity.

Effect of a Multicomponent Intervention on Hepatic Steatosis Is Partially Mediated by the Reduction of Intermuscular Abdominal Adipose Tissue in Children With Overweight or Obesity: The EFIGRO Project.

OBJECTIVE: In adults, there is evidence that improvement of metabolic-associated fatty liver disease (MAFLD) depends on the reduction of myosteatosis. In children, in whom the prevalence of MAFLD is alarming, this muscle-liver crosstalk has not been tested. Therefore, we aimed to explore whether the effects of a multicomponent intervention on hepatic fat is mediated by changes in intermuscular abdominal adipose tissue (IMAAT) in children with overweight/obesity. RESEARCH DESIGN AND METHODS: A total of 116 children with overweight/obesity were allocated to a 22-week family-based lifestyle and psychoeducational intervention (control group, n = 57) or the same intervention plus supervised exercise (exercise group, n = 59). Hepatic fat percentage and IMAAT were acquired by MRI at baseline and at the end of the intervention. RESULTS: Changes in IMAAT explained 20.7% of the improvements in hepatic steatosis (P < 0.05). Only children who meaningfully reduced their IMAAT (i.e., responders) had improved hepatic steatosis at the end of the intervention (within-group analysis: responders -20% [P = 0.005] vs. nonresponders -1.5% [P = 0.803]). Between-group analysis showed greater reductions in favor of IMAAT responders compared with nonresponders (18.3% vs. 0.6%, P = 0.018), regardless of overall abdominal fat loss. CONCLUSIONS: The reduction of IMAAT plays a relevant role in the improvement of hepatic steatosis after a multicomponent intervention in children with overweight/obesity. Indeed, only children who achieved a meaningful reduction in IMAAT at the end of the intervention had a reduced percentage of hepatic fat independent of abdominal fat loss. Our findings suggest that abdominal muscle fat infiltration could be a therapeutic target for the treatment of MAFLD in childhood.

Associations of fitness and physical activity with specific abdominal fat depots in children with overweight/obesity.

OBJECTIVES: To examine the relationship between physical fitness and physical activity (PA) with specific abdominal fat depots and their potential implications for cardiometabolic risk and insulin resistance (IR) in children with overweight/obesity. MATERIALS AND METHODS: A total of 116 children with overweight/obesity (10.7 ± 1.1 year, 54% girls) participated in the study. Abdominal visceral (VAT), subcutaneous (ASAT), and intermuscular abdominal adipose tissue (IMAAT) were assessed by magnetic resonance imaging. The cardiometabolic risk (MetS) score and the insulin resistance homeostasis model assessment (HOMA-IR) were calculated. Health-related physical fitness components (treadmill test, and 20 m shuttle run, handgrip, standing broad jump and 4 × 10 m tests) were evaluated, and PA was measured (accelerometry). Children were categorized as fit or unfit for each specific fitness test, and as active or inactive. RESULTS: Higher VAT, ASAT, and IMAAT were associated with higher MetS score and HOMA-IR (all p < 0.02). A better performance in all fitness tests and total and vigorous PA were strongly associated with lower VAT (all p < 0.04), ASAT (all p < 0.005), and IMAAT (all p < 0.005). Fit or active children had lower VAT, ASAT, and IMAAT (all p < 0.03) than their unfit or inactive counterparts. CONCLUSION: These results reinforce the importance of having adequate fitness and PA levels to reduce abdominal fat accumulation in children. Given that VAT, ASAT, and IMAAT are associated with higher risk of developing cardiovascular diseases and type 2 diabetes, the improvement of physical fitness by the promotion of PA should be goals of lifestyle interventions for improving health in children with overweight/obesity.

The Effect of a Family-Based Lifestyle Education Program on Dietary Habits, Hepatic Fat and Adiposity Markers in 8-12-Year-Old Children with Overweight/Obesity.

Healthy lifestyle education programs are recommended for obesity prevention and treatment. However, there is no previous information on the effects of these programs on the reduction of hepatic fat percentage. The aims were (i) to examine the effectiveness of a 22-week family-based lifestyle education program on dietary habits, and (ii) to explore the associations of changes in dietary intake with percent hepatic fat reduction and adiposity in children with overweight/obesity. A total of 81 children with overweight/obesity (aged 10.6 ± 1.1 years, 53.1% girls) and their parents attended a 22-week family based healthy lifestyle and psychoeducational program accompanied with (intensive group) or without (control) an exercise program. Hepatic fat (magnetic resonance imaging), adiposity (dual energy X-ray absorptiometry) and dietary habits (two non-consecutive 24 h-recalls) were assessed before and after the intervention. Energy (p < 0.01) fat (p < 0.01) and added sugar (p < 0.03) intake were significantly reduced in both groups at the end of the program, while, in addition, carbohydrates intake (p < 0.04) was reduced exclusively in the control group, and simple sugar (p < 0.05) and cholesterol (p < 0.03) intake was reduced in the exercise group. Fruit (p < 0.03) and low-fat/skimmed dairy consumption (p < 0.02), the adherence to the Mediterranean Diet Quality Index for children and teenagers (KIDMED, p < 0.01) and breakfast quality index (p < 0.03) were significantly higher in both control and intervention groups after the intervention. Moreover, participants in the exercise group increased the adherence to the Dietary Approaches to Stop Hypertension (DASH) diet (p < 0.001), whereas the ratio of evening-morning energy intake was significantly lower exclusively in the control group after the program (p < 0.02). Changes in energy intake were significantly associated with changes in fat mass index (FMI) in the exercise group, whereas changes in sugar-sweetened beverages (SSB) consumption was associated with percent hepatic fat reduction (p < 0.05) in the control group. A 22-week family-based healthy lifestyle program seems to be effective on improving diet quality and health in children with overweight/obesity and these should focus on SSB avoidance and physical activity.

Associations of physical activity and fitness with hepatic steatosis, liver enzymes, and insulin resistance in children with overweight/obesity.

BACKGROUND: Non-alcoholic fatty liver disease is the most common liver disease in childhood and is related to insulin resistance and cardiometabolic risk factors. Evidence supporting the association of fitness and physical activity with hepatic fat, liver enzymes, or triglyceride-to-high-density lipoprotein ratio is scarce in children. OBJECTIVE: To analyze the associations of physical fitness and physical activity (PA) with percentage hepatic fat, liver enzymes, insulin resistance, and cardiometabolic risk in children with overweight/obesity. SUBJECTS: A total of 115 children (10.6 ± 1.1 years; 54% girls) with overweight/obesity of the EFIGRO study (ClinicalTrials.gov: NCT02258126) were included in the analyses. METHODS: Cardiorespiratory fitness (CRF), musculoskeletal fitness and speed-agility were measured by the Alpha-fitness tests, and PA by wGT3X-BT accelerometers. Percentage hepatic fat was assessed by magnetic resonance imaging. Alanine aminotransferase (ALT), gamma-glutamyl transferase (GGT), aspartate aminotransferase (AST), insulin, glucose, triglycerides (TG), and high-density lipoprotein (HDL) levels were obtained from fasting blood samples. The homeostasis model assessment insulin resistance (HOMA-IR) and AST/ALT and TG/HDL ratios were calculated. RESULTS: Higher CRF was associated with lower percentage hepatic fat (ß = -0.266, P = .01) and GGT (ß = -0.315, P < .01), and higher AST/ALT ratio (ß = 0.306, P < .01). CRF-fit children have lower GGT levels (15 ± 1 vs 17 ± 1 U/L, CRF-fit vs CRF-unfit children, P = .02), HOMA-IR (2.2 ± 0.1 vs 2.9 ± 0.1, P < .01) and TG/HDL ratio (1.4 ± 0.1 vs 1.9 ± 0.1, P = .01) and higher AST/ALT ratio (1.3 ± 0.0 vs 1.2 ± 0.0, P = .03), than CRF-unfit children. CONCLUSIONS: These findings emphasize the importance of considering the improvement of CRF as a target of programs for preventing hepatic steatosis, type 2 diabetes and cardiovascular diseases in children with overweight.

Hepatic fat content and bone mineral density in children with overweight/obesity.

OBJECTIVES: To examine the influence of non-alcoholic fatty liver disease (NAFLD) and hepatic fat content on bone mineral density (BMD), and to investigate whether the relationship between NAFLD and BMD is independent of lifestyle factors related to BMD. METHODS: Hepatic fat content (magnetic resonance imaging), BMD, lean mass index, total and abdominal fat mass (dual-energy-X-ray absorptiometry), moderate to vigorous physical activity (MVPA) (accelerometry), and calcium and vitamin D intake (two 24 h recalls) were measured in 115 children with overweight/obesity aged 10.6 ± 1.1 years old. RESULTS: Children with NAFLD had lower BMD than children without NAFLD regardless of sex, puberty stage, lean mass index, fat mass, MVPA, and calcium and vitamin D intake (0.89 ± 0.01 vs. 0.93 ± 0.01 g/cm2 for NAFLD and non-NAFLD, respectively, P < 0.01). Higher hepatic fat content was significantly associated with lower BMD regardless of confounders (adjusted P < 0.05). CONCLUSIONS: Findings of the current study suggest that hepatic fat accumulation is associated with decreased BMD independently of adiposity, and regardless of those lifestyle factors closely related to bone mineral accrual in children. These results may have implication in the clinical management of children with overweight/obesity given the high prevalence of pediatric NAFLD.

Prevention of diabetes in overweight/obese children through a family based intervention program including supervised exercise (PREDIKID project): study protocol for a randomized controlled trial.

BACKGROUND: The global pandemic of obesity has led to an increased risk for prediabetes and type-2 diabetes (T2D). The aims of the current project are: (1) to evaluate the effect of a 22-week family based intervention program, including supervised exercise, on insulin resistance syndrome (IRS) risk in children with a high risk of developing T2D and (2) to identify the profile of microRNA in circulating exosomes and in peripheral blood mononuclear cells in children with a high risk of developing T2D and its response to a multidisciplinary intervention program including exercise. METHODS: A total of 84 children, aged 8-12 years, with a high risk of T2D will be included and randomly assigned to control (N = 42) or intervention (N = 42) groups. The control group will receive a family based lifestyle education and psycho-educational program (2 days/month), while the intervention group will attend the same lifestyle education and psycho-educational program plus the exercise program (3 days/week, 90 min per session including warm-up, moderate to vigorous aerobic activities, and strength exercises). The following measurements will be evaluated at baseline prior to randomization and after the intervention: fasting insulin, glucose and hemoglobin A1c; body composition (dual-energy X-ray absorptiometry); ectopic fat (magnetic resonance imaging); microRNA expression in circulating exosomes and in peripheral blood mononuclear cells (MiSeq; Illumina); cardiorespiratory fitness (cardiopulmonary exercise testing); dietary habits and physical activity (accelerometry). DISCUSSION: Prevention and identification of children with a high risk of developing T2D could help to improve their cardiovascular health and to reduce the comorbidities associated with obesity. TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT03027726 . Registered on 16 January 2017.

Multicenter Comparison of Contrast-Enhanced FDG PET/CT and 64-Slice Multi-Detector-Row CT for Initial Staging and Response Evaluation at the End of Treatment in Patients With Lymphoma.

OBJECTIVES: To compare staging correctness between contrast-enhanced FDG PET/ceCT and 64-slice multi-detector-row CT (ceCT64) for initial staging and response evaluation at the end of treatment (EOT) in patients with Hodgkin lymphoma, diffuse large B cell lymphoma (DLBCL), and follicular lymphoma. METHODS: This prospective study compared initial staging and response evaluation at EOT. One hundred eighty-one patients were randomly assigned to either ceCT64 or FDG PET/ceCT. A nuclear medicine physician and a radiologist read FDG PET/ceCT scans independently and achieved post hoc consensus, whereas another independent radiologist interpreted ceCT64 separately. The reference standard included all clinical information, all tests, and follow-up. Ethics committees of the participating centers approved the study, and all participants provided written consent. RESULTS: Ninety-one patients were randomized to ceCT64 and 90 to FDG PET/ceCT; 72 had Hodgkin lymphoma, 72 had DLBCL, and 37 had follicular lymphoma. There was excellent correlation between the reference standard and initial staging for both FDG PET/ceCT (κ = 0.96) and ceCT64 (κ = 0.84), although evaluation of the response at EOT was excellent only for FDG PET/ceCT (κ = 0.91). CONCLUSIONS: Our study demonstrated satisfactory agreement between FDG PET/ceCT (κ = 0.96) and ceCT64 (κ = 0.84) in initial staging compared with the reference standard (P = 0.16). Response evaluation at EOT with FDG PET/ceCT (κ = 0.91) was superior compared with ceCT64 (κ = 0.307) (P < 0.001).

Integrated FDG PET/CT: Utility and Applications in Clinical Oncology.

Accurate diagnosis and staging are essential for an optimal management of cancer patients. Positron emision tomography with 2-deoxy-2-fluorine-18-fluoro-D-glucose ((18)FDG-PET) and, more recently, (18)FDG-PET/computed tomography ((18)FDG-PET/CT) have emerged as powerful imaging tools in oncology, because of the valuable functional information they provide. The combined acquisition of PET and CT has synergistic advantages over its isolated constituents and minimizes their limitations. It decreases examination times by 25%-40%, leads to a higher patient throughput and unificates two imaging procedures in a single session. There is evidence that (18)FDG-PET/CT is a more accurate test than either of its components for the evaluation of various tumors. It is a particularly valuable tool for detection of recurrence, especially in asymptomatic patients with rising tumor markers and those with negative or equivocal findings on conventional imaging tests. Yet, there are some limitations and areas of uncertainty, mainly regarding the lack of specificity of the (18)FDG uptake and the variable (18)FDG avidity of some cancers. This article reviews the advantages, limitations and main applications of (18)FDG-PET/CT in oncology, with especial emphasis on lung cancer, colorectal cancer, lymphomas, melanoma and head and neck cancers.

PET/CT in lymphoma: prospective study of enhanced full-dose PET/CT versus unenhanced low-dose PET/CT.

UNLABELLED: PET/CT combines functional and morphologic data and increases diagnostic accuracy in a variety of malignancies. This study prospectively compares the agreement between contrast-enhanced full-dose PET/CT and unenhanced low-dose PET/CT in lesion detection and initial staging of Hodgkin's disease and non-Hodgkin's lymphoma. METHODS: Forty-seven biopsy-proven lymphoma patients underwent a 18F-FDG PET/CT study that included unenhanced low-dose CT and enhanced full-dose CT for initial staging. Patients who had undergone previous diagnostic CT for initial staging were excluded. For every patient, each modality of PET/CT images was evaluated by either of 2 pairs of readers, with each pair comprising 1 experienced radiologist and 1 experienced nuclear physician. While evaluating one of the 2 types of PET/CT, the readers were unaware of the results of the other type. Lesion detection, number of sites affected in each anatomic region, and disease stage were assessed. Agreement between techniques was determined by the kappa-statistic, and discordances were studied by the McNemar test. Clinical, analytic, histopathologic, diagnostic CT, and PET data; data from other imaging techniques; and follow-up data constituted the reference standard. RESULTS: For region-based analysis, no significant differences were found between unenhanced low-dose PET/CT and contrast-enhanced full-dose PET/CT, although full-dose PET/CT showed fewer indeterminate findings and a higher number of extranodal sites affected than did low-dose PET/CT. Agreement between the 2 types of PET/CT was almost perfect for disease stage (kappa = 0.92; P < 0.001). CONCLUSION: Our study showed a good correlation between unenhanced low-dose PET/CT and contrast-enhanced full-dose PET/CT for lymph node and extranodal disease in lymphomas, suggesting that unenhanced low-dose PET/CT might suffice in most patients as the only imaging technique for the initial staging of lymphomas, reserving diagnostic CT for selected cases.

Positron emission tomography/computed tomography: diagnostic accuracy in lymphoma.

An accurate initial staging of patients with non-Hodgkin lymphoma (NHL) and Hodgkin lymphoma (HL) is critical for the selection of an appropriate treatment. Computed tomography (CT) remains the standard imaging technique, although it is based on anatomic criteria. Positron emission tomography (PET) with 2-deoxy-2-[fluorine-18]fluoro-d-glucose (FDG) provides useful functional information but requires anatomical correlation to localise lesions accurately. We have prospectively compared the accuracy of combined PET/CT with that of CT and PET alone at initial staging in lymphoma patients. Forty-seven newly diagnosed patients were evaluated. PET/CT was superior compared with CT and PET in nodal evaluation and detection of extranodal disease. Using a staging algorithm with PET/CT resulted in the disease stage being increased in 11 of 47 patients (10 NHL and 1 HL) (McNemar test P = 0.012). Therefore, a different treatment strategy based on PET/CT findings was suggested for seven patients (14.8%). PET/CT markedly improves accuracy in the diagnostic work-up of patients with lymphoma.

Positron emission tomography/computed tomography in the management of Hodgkin's disease and non-Hodgkin's lymphoma.

The incidence of Hodgkin's disease (HD) and Non-Hodgkin's lymphoma (NHL) is around 8% of all malignancies. Fortunately, HD and NHL are among the few malignancies that are potentially curable with current existing treatment modalities, even in advanced or recurrent disease. Accurate staging, early therapy monitoring, and posttreatment evaluation of lymphomas are important for optimum management of these patients. We reviewed the imaging findings of patients with histologically proved lymphoma who underwent staging positron emission tomography/computed tomography (PET/CT), early monitoring therapy PET/CT (after 3 cycles of chemotherapy), and posttreatment PET/CT. PET/CT imaging findings are shown. Utility of PET/CT in recognizing false-positive and false-negative cases of CT and PET alone is addressed. Pitfalls and diagnostic difficulties are analyzed. PET/CT is a new imaging technology that improves the evaluation of lymphoma. This review will help the reader to better understand the imaging findings and applications of PET/CT in the management of lymphoma.

Correlation between the measurement of transverse diameter in the proximal neck on computed tomography and on aortography before endovascular treatment of infrarenal aortic aneurysm.

The aim of this study was to determine the correlation between the measurement of transverse diameter of the proximal neck on computed tomographic angiography (CTA) and graduated catheter aortography in patients who are candidates for endovascular graft placement in order to replace, if both measurements are equivalent, aortography for CTA alone. Preoperative dual-slice CTA and graduated catheter aortography were performed in 35 consecutive patients with infrarenal aortic aneurysm within 10 days. Transverse proximal neck diameters were measured on a true axial section on CTA reconstructions and on aortographic images, always 6 mm distal from the most inferior main renal artery. Mean, median, and standard deviation were obtained and the measurements correlated for each patient using Pearson's correlation and linear regression analysis. A significant difference in proximal neck transverse diameter measurements was found between graduated catheter aortography and CTA in all cases. CTA values were a mean of 1.74 mm higher than aortography values. Pearson's correlation indicates a strong correlation between both techniques, and a regression equation determines the predictive value of aortography on the basis of CTA values. Estimation of the transverse diameter of the proximal neck on aortography on the basis of that obtained on CTA allows us to affirm that CTA could be used as the sole method for the preoperative selection of appropriate endograft size in patients with infrarenal aortic aneurysm.