A Multidisciplinary Approach to Pediatric Obesity Shows Improvement Postintervention.

OBJECTIVE: Outpatient management of pediatric obesity can be difficult, requiring a significant time commitment from both provider and patient. Multidisciplinary clinic-based programs have shown promising effects in reducing BMI during intervention, but whether these changes are sustained over time is not well studied. The purpose of this study was to determine the post-treatment outcomes of children seen in a multidisciplinary pediatric obesity clinic (MPOC). METHODS: A retrospective chart review was performed using the MPOC database, which included all clinic patients from January 2008 to August 2016 who attended a minimum of 2 visits (n = 472). The primary outcome was the absolute change in BMI Z-score (BMIZ) from the final intervention visit compared to 1- and 2-years post-intervention. Multivariate regression analysis was performed to characterize predictors of change in BMIZ. RESULTS: MPOC patients ranged in age from 3 to 18 years. Mean BMIZ decreased significantly during intervention (-0.13 ± 1.47, P < .001) and was maintained at 1- and 2-years post-intervention. In participants ages 3 to 5, BMIZ further decreased at 1 year post intervention (-0.27 ± 0.26, P < .001). Age at time of referral was the only significant predictor of change in BMIZ. CONCLUSIONS: Outpatient, multidisciplinary intervention for pediatric obesity was effective in reducing or stabilizing BMIZ during and beyond the intervention, particularly when patients were referred at an early age. Although primary prevention is the ideal management, multidisciplinary clinic intervention can be effective in the sustained treatment of pediatric obesity.

Providing Gender-Affirmative Care During the Severe Acute Respiratory Syndrome Coronavirus 2 Pandemic Era: Experiences and Perspectives from Pediatric Endocrinologists in the United States.

Transgender and gender diverse (TGD) youth are at risk of worsened health disparities during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. Health care delivery by pediatric endocrinologists, including rapid implementation of telemedicine services, during the pandemic has not been documented. The Pediatric Endocrine Society's Transgender Health Special Interest Group met virtually to survey practice patterns during the SARS-CoV-2 pandemic. The majority of pediatric endocrinologists continued to provide most aspects of medical transition; however, we also identified several barriers to care. Overall, the survey results demonstrated that telemedicine can be utilized as an effective way to provide gender-affirming medical care to TGD youth.

Improved free-breathing liver fat and iron quantification using a 2D chemical shift-encoded MRI with flip angle modulation and motion-corrected averaging.

OBJECTIVES: 3D chemical shift-encoded (CSE) MRI enables accurate and precise quantification of proton density fat fraction (PDFF) and R2*, biomarkers of hepatic fat and iron deposition. Unfortunately, 3D CSE-MRI requires reliable breath-holding. Free-breathing 2D CSE-MRI with sequential radiofrequency excitation is a motion-robust alternative but suffers from low signal-to-noise-ratio (SNR). To overcome this limitation, this work explores the combination of flip angle-modulated (FAM) 2D CSE imaging with a non-local means (NLM) motion-corrected averaging technique. METHODS: In this prospective study, 35 healthy subjects (27 children/8 adults) were imaged on a 3T MRI-system. Multi-echo 3D CSE ("3D") and 2D CSE FAM ("FAM") images were acquired during breath-hold and free-breathing, respectively, to obtain PDFF and R2* maps of the liver. Multi-repetition FAM was postprocessed with direct averaging (DA)- and NLM-based averaging and compared to 3D CSE using Bland-Altmann and regression analysis. Image qualities of PDFF and R2* maps were reviewed by two radiologists using a Likert-like scale (score 1-5, 5 = best). RESULTS: Compared to 3D CSE, multi-repetition FAM-NLM showed excellent agreement (regression slope = 1.0, R2 = 0.996) for PDFF and good agreement (regression slope 1.08-1.15, R2 ≥ 0.899) for R2*. Further, multi-repetition FAM-NLM PDFF and R2* maps had fewer artifacts (score 3.8 vs. 3.2, p < 0.0001 for PDFF; score 3.2 vs. 2.6, p < 0.001 for R2*) and better overall image quality (score 4.0 vs. 3.5, p < 0.0001 for PDFF; score 3.4 vs. 2.7, p < 0.0001 for R2*). CONCLUSIONS: Free-breathing FAM-NLM provides superior image quality of the liver compared to the conventional breath-hold 3D CSE-MRI, while minimizing bias for PDFF and R2* quantification. KEY POINTS: • 2D CSE FAM-NLM is a free-breathing method for liver fat and iron quantification and viable alternative for patients unable to hold their breath. • 2D CSE FAM-NLM is a feasible alternative to breath-hold 3D CSE methods, with low bias in proton density fat fraction (PDFF) and no clinically significant bias in R2*. • Quantitatively, multiple repetitions in 2D CSE FAM-NLM lead to improved SNR.

Motion-robust, high-SNR liver fat quantification using a 2D sequential acquisition with a variable flip angle approach.

PURPOSE: Chemical shift encoded (CSE)-MRI enables quantification of proton-density fat fraction (PDFF) as a biomarker of liver fat content. However, conventional 3D Cartesian CSE-MRI methods require breath-holding. A motion-robust 2D Cartesian sequential method addresses this limitation but suffers from low SNR. In this work, a novel free breathing 2D Cartesian sequential CSE-MRI method using a variable flip angle approach with centric phase encoding (VFA-centric) is developed to achieve fat quantification with low T1 bias, high SNR, and minimal blurring. METHODS: Numerical simulation was performed for variable flip angle schedule design and preliminary evaluation of VFA-centric method, along with several alternative flip angle designs. Phantom, adults (n = 8), and children (n = 27) were imaged at 3T. Multi-echo images were acquired and PDFF maps were estimated. PDFF standard deviation was used as a surrogate for SNR. RESULTS: In both simulation and phantom experiments, the VFA-centric method enabled higher SNR imaging with minimal T1 bias and blurring artifacts. High correlation (slope = 1.00, intercept = 0.04, R2 = 0.998) was observed in vivo between the proposed VFA-centric method obtained PDFF and reference PDFF (free breathing low-flip angle 2D sequential acquisition). Further, the proposed VFA-centric method (PDFF standard deviation = 1.5%) had a better SNR performance than the reference acquisition (PDFF standard deviation = 3.3%) with P < .001. CONCLUSIONS: The proposed free breathing 2D Cartesian sequential CSE-MRI method with variable flip angle approach and centric-ordered phase encoding achieved motion robustness, low T1 bias, high SNR compared to previous 2D sequential methods, and low blurring in liver fat quantification.

At the Margins: Comparing School Experiences of Nonbinary and Binary-Identified Transgender Youth.

BACKGROUND: Transgender, nonbinary, and gender nonconforming (TNG) young people are a diverse group, including young people with gender identities beyond the gender binary. Whereas nonbinary youth experience disparities in victimization and mental health, school belonging, support, and resources have not been well described. METHODS: We conducted an online survey of TNG young people (ages 12-22) in Wisconsin to assess school belonging, safety, support, and resources. We compared responses among participants with nonbinary versus binary identities using mulvariate analysis of variance, multivariate analysis of covariance, chi-square and logistic regression analysis. RESULTS: A total of 287 TNG young people met inclusion criteria (average age 18.2 ± 2.5 years). More than 40% of participants identified as nonbinary. Nonbinary participants were less likely to be out to teachers, but more likely to utilize supportive staff as a resource compared to binary-identified TNG peers. There were no significant differences in school safety and belonging. CONCLUSIONS: Most school experiences do not vary significantly between TNG young people with binary versus nonbinary gender identities, though nonbinary young people are less likely to be out at school. Future research should examine factors that impact whether nonbinary young people share their gender identity and access school support services.

Potential association between type 1 diabetes mellitus and gender dysphoria.

BACKGROUND/OBJECTIVE: Multiple factors have been proposed to explain the increasing prevalence of type 1 diabetes mellitus (T1DM), including psychological stress. The prevalence of gender dysphoria (GD) in youth is also growing. Identifying environmental triggers, such as psychological minority stress experienced by youth with GD, that may influence the pathogenesis and management of T1DM could have important clinical implications. The objective of this study was to determine the prevalence of concurrent diagnosis of T1DM and GD in adolescents evaluated at a university-based children's hospital. METHODS: An electronic data extraction was conducted at the University of Wisconsin Hospital and Clinics from 1 November 2007 to 1 November 2017. Inclusion criteria included age 10 to 21 years and diagnosis of T1DM and/or GD. Prevalence rates were calculated for T1DM and GD. For adolescents with T1DM and GD, information related to diagnosis, treatment, and psychiatric history was collected. RESULTS: The prevalence for T1DM was 2.69 per 1000; the prevalence for GD was 0.42 per 1000. Eight adolescents had T1DM and GD. In adolescents with GD, the prevalence of T1DM was 9.4-fold higher than the prevalence of T1DM alone (24.77 vs 2.68 per 1000). Five adolescents were seen in GD clinic and their glycemic control initially improved after the first GD clinic visit. CONCLUSIONS: There was an increased prevalence of a concurrent diagnosis of T1DM in those with GD compared to the general population. Glycemic control improved after the first GD clinic visit in adolescents with T1DM and GD, which may be secondary to stress reduction.

Curative potential of allogeneic hematopoietic stem cell transplant in type 1 diabetes.

The mainstay of treatment for type 1 diabetes (T1D) is exogenous insulin. Here, we report a case in which exogenous insulin requirements were eliminated after an allogeneic hematopoietic stem cell transplant for aplastic anemia in a pediatric patient recently diagnosed with T1D, and explore the validity of this approach compared with current treatments.

In Nonobese Girls, Waist Circumference as a Predictor of Insulin Resistance Is Comparable to MRI Fat Measures and Superior to BMI.

OBJECTIVE: The aim of this study was to investigate the degree to which waist circumference (WC), body mass index (BMI), and magnetic resonance imaging (MRI)-measured abdominal fat deposition predict insulin resistance (IR) in nonobese girls of diverse racial and ethnic backgrounds. METHODS: Fifty-seven nonobese girls (12 African-American, 16 Hispanic White, and 29 non-Hispanic White girls) aged 11-14 years were assessed for WC, MRI hepatic proton density fat fraction, visceral and subcutaneous adipose tissue volume, BMI Z-score, fasting insulin, homeostasis model of assessment (HOMA)-IR, adiponectin, leptin, sex hormone-binding globulin, high-density lipoprotein cholesterol, and triglycerides. RESULTS: Univariate and multivariate analyses adjusted for race and ethnicity indicated that only WC and visceral adipose tissue volume were independent predictors of fasting insulin and HOMA-IR, while hepatic proton density fat fraction, BMI Z-score, and subcutaneous adipose tissue volume were dependent predictors. Hispanic White girls showed significantly higher mean fasting insulin and HOMA-IR and lower sex hormone-binding globulin than non-Hispanic White girls (p < 0.01). CONCLUSIONS: In nonobese girls of diverse racial and ethnic backgrounds, WC, particularly when adjusted for race or ethnicity, is an independent predictor of IR comparable to MRI-derived measurements of fat and superior to the BMI Z-score.

Proton density fat-fraction is an accurate biomarker of hepatic steatosis in adolescent girls and young women.

OBJECTIVES: To compare complex quantitative magnetic resonance imaging (MRI) with MR spectroscopy (MRS) for quantification of hepatic steatosis (HS) and determine clinically significant MRI-based thresholds of HS in female youths. METHODS: This prospective, cross-sectional study was conducted in 132 healthy females (11-22 years, mean 13.3 ± 2). Proton density fat-fraction (PDFF) was measured using complex quantitative MRI and MRS. Body mass index (BMI), fasting labs [glucose, insulin, alanine aminotransferase (ALT), and other metabolic markers] were obtained. Outcomes were measured using regression analysis, Spearman-rank correlation, and receiver operator characteristics (ROC) analysis. HS was defined as MRI-PDFF >5.6%. RESULTS: HS was detected by MRI-PDFF in 15% of all subjects. Linear regression demonstrated excellent correlation and agreement [r(2) = 0.96, slope = 0.97 (95 %CI: 0.94-1.00), intercept = 0.78% (95 %CI: 0.58-0.98%)] between MRI-PDFF and MRS-PDFF. MRI-PDFF had a sensitivity of 100% (95 %CI: 0.79-1.00), specificity of 96.6% (95 %CI: 0.91-0.99), and a kappa index of 87% (95 %CI: 0.75-0.99) for identifying HS. In overweight subjects with HS, MRI-PDFF correlated with ALT (r = 0.84, p < 0.0001) and insulin (r = 0.833, p < 0.001), but not with BMI or WC. ROC analysis ascertained an optimal MRI-PDFF threshold of 3.5% for predicting metabolic syndrome (sensitivity = 76 %, specificity = 83 %). CONCLUSION: Complex quantitative MRI demonstrates strong correlation and agreement with MRS to quantify hepatic triglyceride content in adolescent girls and young women. A low PDFF threshold is predictive of metabolic syndrome in this population. KEY POINTS: • Confounder-corrected quantitative MRI (ccqMRI) effectively measures hepatic triglyceride content in adolescent girls. • MRS and ccqMRI strongly correlate in liver proton density fat-fraction (PDFF) detection. • A PDFF threshold of 3.5% may be predictive of paediatric metabolic syndrome.

Quantification of liver fat with respiratory-gated quantitative chemical shift encoded MRI.

PURPOSE: To evaluate free-breathing chemical shift-encoded (CSE) magnetic resonance imaging (MRI) for quantification of hepatic proton density fat-fraction (PDFF). A secondary purpose was to evaluate hepatic R2* values measured using free-breathing quantitative CSE-MRI. MATERIALS AND METHODS: Fifty patients (mean age, 56 years) were prospectively recruited and underwent the following four acquisitions to measure PDFF and R2*; 1) conventional breath-hold CSE-MRI (BH-CSE); 2) respiratory-gated CSE-MRI using respiratory bellows (BL-CSE); 3) respiratory-gated CSE-MRI using navigator echoes (NV-CSE); and 4) single voxel MR spectroscopy (MRS) as the reference standard for PDFF. Image quality was evaluated by two radiologists. MRI-PDFF measured from the three CSE-MRI methods were compared with MRS-PDFF using linear regression. The PDFF and R2* values were compared using two one-sided t-test to evaluate statistical equivalence. RESULTS: There was no significant difference in the image quality scores among the three CSE-MRI methods for either PDFF (P = 1.000) or R2* maps (P = 0.359-1.000). Correlation coefficients (95% confidence interval [CI]) for the PDFF comparisons were 0.98 (0.96-0.99) for BH-, 0.99 (0.97-0.99) for BL-, and 0.99 (0.98-0.99) for NV-CSE. The statistical equivalence test revealed that the mean difference in PDFF and R2* between any two of the three CSE-MRI methods was less than ±1 percentage point (pp) and ±5 s(-1) , respectively (P < 0.046). CONCLUSION: Respiratory-gated CSE-MRI with respiratory bellows or navigator echo are feasible methods to quantify liver PDFF and R2* and are as valid as the standard breath-hold technique.

Complexity in the diagnosis and management of 45,X Turner Syndrome mosaicism.

Diagnosis, decision making, and counseling for patients with disorders of sexual development pose challenges for physicians and families. Accurate antenatal evaluation combined with effective communication between the family and multidisciplinary team is important to provide the best patient outcome. We reviewed 2 cases from our institution that illustrate the complexity of antenatal and postnatal management in Turner Syndrome patients who have 45,X mosaicism. We concluded that because of the complexity involved in providing appropriate care to these individuals, it is critical that accurate and universally accessible counseling materials are available to providers and families at the time of diagnosis and management decision making.

Predicting hepatic steatosis in a racially and ethnically diverse cohort of adolescent girls.

OBJECTIVE: To develop a risk assessment model for early detection of hepatic steatosis using common anthropometric and metabolic markers. STUDY DESIGN: This was a cross-sectional study of 134 adolescent and young adult females, age 11-22 years (mean 13.3±2 years) from a middle school and clinics in Madison, Wisconsin. The ethnic distribution was 27% Hispanic and 73% non-Hispanic; the racial distribution was 64% Caucasian, 31% African-American, and 5% Asian, Fasting glucose, fasting insulin, alanine aminotransferase (ALT), body mass index (BMI), waist circumference (WC), and other metabolic markers were assessed. Hepatic fat was quantified using magnetic resonance imaging proton density fat fraction (MR-PDFF). Hepatic steatosis was defined as MR-PDFF>5.5%. Outcome measures were sensitivity, specificity, and positive predictive value (PPV) of BMI, WC, ALT, fasting insulin, and ethnicity as predictors of hepatic steatosis, individually and combined, in a risk assessment model. Classification and regression tree methodology was used to construct a decision tree for predicting hepatic steatosis. RESULTS: MR-PDFF revealed hepatic steatosis in 16% of subjects (27% overweight, 3% nonoverweight). Hispanic ethnicity conferred an OR of 4.26 (95% CI, 1.65-11.04; P=.003) for hepatic steatosis. BMI and ALT did not independently predict hepatic steatosis. A BMI>85% combined with ALT>65 U/L had 9% sensitivity, 100% specificity, and 100% PPV. Lowering the ALT value to 24 U/L increased the sensitivity to 68%, but reduced the PPV to 47%. A risk assessment model incorporating fasting insulin, total cholesterol, WC, and ethnicity increased sensitivity to 64%, specificity to 99% and PPV to 93%. CONCLUSION: A risk assessment model can increase specificity, sensitivity, and PPV for identifying the risk of hepatic steatosis and guide the efficient use of biopsy or imaging for early detection and intervention.

Ethnic differences in the effects of hepatic fat deposition on insulin resistance in nonobese middle school girls.

OBJECTIVE: In nonobese youth, to investigate whether hepatic fat deposition and its metabolic consequences vary between ethnic groups. DESIGN AND METHODS: Thirty-two nonobese girls (12 Hispanic White [H] and 20 non-Hispanic White [NHW] girls), aged 11-14 years old were recruited. Outcome measures were MRI measured hepatic proton density fat fraction (hepatic PDFF), BMI Z-score, waist circumference, fasting insulin, glucose, adiponectin, sex hormone-binding globulin [SHBG], ALT, AST, triglycerides, and HOMA-IR. RESULTS: There were no significant differences in mean BMI Z-scores (P = 0.546) or hepatic PDFF (P = 0.275) between H and NHW girls; however, H girls showed significant correlations between hepatic PDFF and markers of IR (fasting insulin, HOMA-IR, adiponectin, SHBG, triglycerides; all P < 0.05), while NHW girls showed no significant correlations. Matched by hepatic PDFF or BMI Z-score, H girls had more evidence of IR for a given hepatic PDFF (mean insulin, HOMA-IR, and SHBG; all P < 0.05) or BMI Z-score (mean insulin and HOMA-IR; all P < 0.01) than NHW girls. CONCLUSIONS: In nonobese female youth, ethnicity-related differences in effects of hepatic fat on IR are evident, so that in H girls, a given amount of hepatic fat appears to result in a more predictable and greater degree of IR than in NHW girls.

Adipose tissue MRI for quantitative measurement of central obesity.

PURPOSE: To validate adipose tissue magnetic resonance imaging (atMRI) for rapid, quantitative volumetry of visceral adipose tissue (VAT) and total adipose tissue (TAT). MATERIALS AND METHODS: Data were acquired on normal adults and clinically overweight girls with Institutional Review Board (IRB) approval/parental consent using sagittal 6-echo 3D-spoiled gradient-echo (SPGR) (26-sec single-breath-hold) at 3T. Fat-fraction images were reconstructed with quantitative corrections, permitting measurement of a physiologically based fat-fraction threshold in normals to identify adipose tissue, for automated measurement of TAT, and semiautomated measurement of VAT. TAT accuracy was validated using oil phantoms and in vivo TAT/VAT measurements validated with manual segmentation. Group comparisons were performed between normals and overweight girls using TAT, VAT, VAT-TAT-ratio (VTR), body-mass-index (BMI), waist circumference, and waist-hip-ratio (WHR). RESULTS: Oil phantom measurements were highly accurate (<3% error). The measured adipose fat-fraction threshold was 96% ± 2%. VAT and TAT correlated strongly with manual segmentation (normals r(2) ≥ 0.96, overweight girls r(2) ≥ 0.99). VAT segmentation required 30 ± 11 minutes/subject (14 ± 5 sec/slice) using atMRI, versus 216 ± 73 minutes/subject (99 ± 31 sec/slice) manually. Group discrimination was significant using WHR (P < 0.001) and VTR (P = 0.004). CONCLUSION: The atMRI technique permits rapid, accurate measurements of TAT, VAT, and VTR.