COVID-19 related multisystem inflammatory syndrome in children (MIS-C): a case series from a tertiary care pediatric hospital in Qatar.

BACKGROUND: Multisystem Inflammatory Syndrome in Children (MIS-C) is a severe complication of coronavirus disease 2019 (COVID-19) in children, which is increasingly being reported worldwide. Here we report the first case series of 7 children diagnosed with MIS-C in Qatar. METHODS: Clinical features and outcomes of COVID-19 positive patients admitted to Sidra Medicine, Qatar from June to October 2020, who met the WHO case definition for MIS-C were reviewed. RESULTS: The mean age in our case series was 5.6 years, of which 71.4% were males. All patients were previously healthy but had a history of COVID-19 infection. Fever, rash, vomiting and abdominal pain were the most common symptoms (70-100%). The average hospitalization was 12.9 days with no case fatalities. Laboratory findings included lymphopenia and thrombocytopenia in most patients, as well as evidence of coagulopathy and elevated inflammatory markers such as C-reactive protein, ferritin and procalcitonin. Many patients (71.4%) required inotropic support in intensive care, while only one required respiratory support. Although all patients had elevated cardiac biomarkers, cardiovascular involvement was observed in 42.9% of patients with one patient developing a giant coronary aneurysm. All patients received intravenous immunoglobulin (IVIG) and 86% of patients received corticosteroids, with two patients requiring treatment with IL-1 inhibitors. CONCLUSIONS: Our report is one of the first reports on MIS-C from Asia. Although clinical features and outcomes are not significantly different from those reported elsewhere, lack of case fatalities in our cohort may indicate that early recognition and prompt medical attention is necessary for a favorable outcome in MIS-C.

Obese Youth Demonstrate Altered Landing Knee Mechanics Unrelated to Lower-Extremity Peak Torque When Compared With Healthy Weight Youth.

Obese (OB) youth demonstrate altered knee mechanics and worse lower-extremity performance compared with healthy weight (HW) youth. Our objectives were to compare sagittal plane knee landing mechanics between OB and HW youth and to examine the associations of knee and hip extension peak torque with landing mechanics in OB youth. Twenty-four OB and 24 age- and sex-matched HW youth participated. Peak torque was measured and normalized to leg lean mass. Peak knee flexion angle and peak internal knee extension moment were measured during a single-leg hop landing. Paired t tests, Pearson correlation coefficients, and Bonferroni corrections were used. OB youth demonstrated worse performance and lower knee extension (OB: 12.76 [1.38], HW: 14.03 [2.08], P = .03) and hip extension (OB: 8.59 [3.13], HW: 11.10 [2.89], P = .005) peak torque. Furthermore, OB youth demonstrated lower peak knee flexion angles (OB: 48.89 [45.41 to 52.37], HW: 56.07 [52.59 to 59.55], P = .02) and knee extension moments (OB: -1.73 [-1.89 to -1.57], HW: -2.21 [-2.37 to -2.05], P = .0001) during landing compared with HW youth. Peak torque measures were not correlated with peak knee flexion angle nor internal knee extension moment during landing in either group (P > .01). OB youth demonstrated altered landing mechanics compared with HW youth. However, no associations among peak torque measurements and knee landing mechanics were present.

Autoimmune thyroid diseases, autoimmune hepatitis, celiac disease and type 1 diabetes mellitus in pediatric systemic lupus erythematosus: Results from the CARRA Legacy Registry.

OBJECTIVE: Polyautoimmunity (PA) with systemic lupus erythematosus (SLE) is reported as a poor prognostic factor, but little is known about its effect in childhood-onset SLE (cSLE). We describe PA in cSLE within the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Legacy Registry and evaluate its association to lupus disease outcomes. METHODS: CARRA Legacy Registry is the largest pediatric rheumatology registry that collected data at enrollment and every 6 months thereafter. We describe the co-occurrence of selected autoimmune disorders (autoimmune thyroid diseases, autoimmune hepatitis, celiac disease and type 1 diabetes mellitus) in cSLE. To assess outcomes, we studied measures of lupus disease activity, complications, and patient's quality of life (QoL). Comparisons by PA status were made using chi-square, Fisher's exact test, two-sample t-tests, Wilcoxon rank sum tests, and mixed effects models as appropriate. RESULTS: 1285 patients met the American College of Rheumatology criteria for SLE. Of those, 388 (30%) had data on comorbidity. The prevalence of PA was 8.8%. Patients with PA reported more hospitalizations and aggressive immunotherapy use. SLEDAI and PGA scores improved over time, but did not differ by PA status. No significant differences were found in QoL measures or their trajectory over time by PA status. CONCLUSION: In cSLE, PA is associated with more hospitalizations and aggressive immunotherapy use. Although lupus disease activity improved over time, patients' QoL neither improved over time nor differed by having other autoimmune disease. Prospective, case-control, long-term follow-up studies on cSLE are needed to validate our results. MESH KEY INDEXING TERMS: Pediatric systemic lupus erythematosus; Autoimmune diseases; Outcome assessment.

A preliminary evaluation of the associations among functional performance tasks and quality of life in obese and healthy weight youth.

The associations among lower extremity functional performance and quality of life in obese youth are unknown. The aims of this study were to compare lower extremity strength, lower extremity functional performance, and health related quality of life between obese and healthy-weight youth and evaluate the relationships between lower extremity performance and health related quality of life in obese youth. Twenty obese and 20 age and sex matched healthy-weight youth were recruited. Peak torque of the major lower extremity muscles were measured. Functional performance was measured with single leg hop and single leg balance tests. The Paediatric Quality of Life questionnaire's physical and psychosocial health subscales were used. Paired t-tests and multiple regression analyses were performed. Obese youth demonstrated decreased peak torque in all muscles measured (P < 0.05), poorer functional performance (P < 0.05), and worse physical health related quality of life (P < 0.05) compared to healthy-weight youth. Lower extremity functional performance was associated with aspects of quality of life in the obese group (P = 0.002), but not in the healthy-weight group (P < 0.05). These results may assist in encouraging best practices in the promotion of exercise, physical activity, and quality of life in obese youth.

Healthcare Use Patterns and Economic Burden of Chronic Musculoskeletal Pain in Children before Diagnosis.

OBJECTIVES: To evaluate the healthcare use and costs of amplified musculoskeletal pain syndrome (AMPS) in children before diagnosis. STUDY DESIGN: We performed a retrospective study in children with AMPS at a pediatric rheumatology clinic between 2010 and 2014. Data were abstracted on 80 patients after primary rheumatic diseases were excluded. Healthcare visits, medications and diagnostic testing that occurred in the years before diagnosis were collected. The Medical Expenditure Panel Survey was used to estimate visit costs. RESULTS: Patients were adolescent females (89%) and white (86%). The median time to diagnosis was 10.2 months. The median pain score was 6.5 and the median Childhood Health Assessment Questionnaire score was 1.1. In this cohort, 29% had at least 1 ED visit and 5% were hospitalized. All patients saw a rheumatologist and 41% had visited another specialist, typically orthopedics and sports medicine. More than one-half had at least 1 radiographic study and 21% had at least 1 magnetic resonance imaging. The total cost for office, emergency department, and hospital visits for AMPS in all 80 patients was $152 853. The mean cost per patient over the entire study period (2008-2014) was $1911 ± $3808, and 43% of costs were outpatient visits. CONCLUSIONS: Children with AMPS have high levels of disability and take a long time to be diagnosed. As a result, even before diagnosis, they have high levels of healthcare use, diagnostic testing, and medical costs. Early recognition of disability and quicker referral to trained subspecialists may improve the prognosis, reduce unnecessary testing, and reduce the overall costs of healthcare.

Diagnosis of systemic-onset juvenile idiopathic arthritis after treatment for presumed Kawasaki disease.

OBJECTIVES: To estimate the incidence of systemic-onset juvenile idiopathic arthritis (SoJIA) within 6 months after treatment for presumed Kawasaki disease (KD) (presumed patients with KD with subsequent diagnosis of SoJIA [pKD/SoJIA]) and describe presentation differences from sole KD. STUDY DESIGN: We identified patients treated for KD at Nationwide Children's Hospital and from the Pediatric Health Information System from 2009-2013. We then identified the subset of children, pKD/SoJIA, who received an International Classification of Diseases, Ninth Revision code for SoJIA and had it listed at least once 3 months after and within 6 months after KD diagnosis. Demographic characteristics, readmission rates, treatments, and complications were noted. A literature review was also performed to identify clinical, laboratory, and echocardiographic data of previously documented patients with KD later diagnosed with SoJIA. RESULTS: There were 6745 total treated patients with KD in the Pediatric Health Information System database during the study period; 10 patients were identified to have pKD/SoJIA (0.2% of cohort). Those with pKD/SoJIA were predominantly Caucasian compared with patients with KD (90% and 46.8%, respectively; P=.003). Macrophage activation syndrome was more common in patients with pKD/SoJIA than in sole patients with KD (30% and 0.30%, respectively; P<.001). Fifteen cases of pKD/SoJIA were identified by literature and chart review, 12 of whom were initially diagnosed with incomplete KD. CONCLUSIONS: We reported a 0.2% incidence of pKD/SoJIA, which was associated with Caucasian race, macrophage activation syndrome, and an incomplete KD phenotype.

Lower extremity pain is associated with reduced function and psychosocial health in obese children.

BACKGROUND: Childhood obesity is associated with reduced quality of life, physical fitness, and a higher prevalence of lower extremity (LE) pain; however, it is unclear whether and how these factors are related. QUESTIONS/PURPOSES: For this study we asked if obese children with LE pain (LE+) had higher BMI-Z scores, lower physical function and psychosocial health, and lower physical fitness compared with obese children without LE pain (LE-). We determined the association of BMI-Z score with physical function, psychosocial health, or physical fitness in obese children. METHODS: Medical charts of 183 obese children were reviewed. Recorded data included anthropometrics, demographics, reports of musculoskeletal pain, Pediatric Quality of Life (PedsQL)-Physical Function score, PedsQL-Psychosocial Health score, and physical fitness levels. Data from 175 individuals were included in the analysis, with 51 in the LE+ group and 124 in the LE- group. Statistical analysis included Mann-Whitney U tests and Spearman's rank order correlations. RESULTS: Between the LE+ and LE- groups, BMI-Z and physical fitness scores were not different. The LE+ group scored worse on the PedsQL-Physical Function scale (LE+: 72.4 [17.1], LE-: 79.5 [15.0]) and PedsQL-Psychosocial Health scale (LE+: 70.0 [16.1], LE-: 75.8 [16.3]). BMI-Z scores negatively correlated with PedsQL-Physical Function scores, PedsQL-Psychosocial Health scores, and physical fitness scores. CONCLUSIONS: Our findings indicate that LE pain should be considered in the evaluation and management of children who are obese. LEVEL OF EVIDENCE: Level III, prognostic study. See Guidelines for Authors for a complete description of levels of evidence.

Exploring the differential diagnosis of joint complaints in pediatric patients with inflammatory bowel disease.

About one quarter of children with inflammatory bowel disease (IBD) experience an extraintestinal manifestation, with the most common being arthritis or arthralgia. Because of the frequency of these joint complaints and their effect on quality of life, it is important to consider all possible etiologies in order to promptly evaluate, diagnose, and possibly refer to other specialists. Pediatric gastroenterologist and IBD specialists are cognizant of the extraintestinal joint manifestations, but may be less familiar with rheumatic disease and the musculoskeletal examination. We explore the differential diagnosis of joint complaints in children, with a focus on IBD-related disease and rheumatic disease.

Pilot Study of the Juvenile Dermatomyositis Consensus Treatment Plans: A CARRA Registry Study.

OBJECTIVES: To determine the feasibility of comparing the Childhood Arthritis and Rheumatology ResearchAlliance (CARRA) consensus treatment plans (CTP) in treating moderate new-onset juvenile dermatomyositis (JDM) using the CARRA registry, and to establish appropriate analytic methods to control for confounding by indication and missing data. METHODS: A pilot cohort of 39 patients with JDM from the CARRA registry was studied. Patients were assigned by the treating physician, considering patient/family preferences, to 1 of 3 CTP: methotrexate (MTX) and prednisone (MP); intravenous (IV) methylprednisolone, MTX, and prednisone (MMP); or IV methylprednisolone, MTX, prednisone, and IV immunoglobulin (MMPI). The primary outcome was the proportion of patients achieving moderate improvement at 6 months under each CTP. Statistical methods including multiple imputation and inverse probability of treatment weighting were used to handle missing data and confounding by indication. RESULTS: Patients received MP (n = 13), MMP (n = 18) and MMPI (n = 8). Patients in all CTP had significant improvement in disease activity. Of the 36 patients who remained in our pilot study at 6 months, 16 (44%) of them successfully achieved moderate improvement at 6 months (6/13, 46% for MP; 7/15, 47% for MMP; 3/8, 38% for MMPI). After correcting for confounding, there were no statistically significant pairwise differences between the CTP (P = 0.328-0.88). CONCLUSION: We gained valuable experience and insight from our pilot study that can be used to guide the design and analysis of comparative effectiveness studies using the CARRA registry CTP approach. Our analytical methods can be adopted for future comparative effectiveness studies and applied to other rare disease observational studies.

Randomized clinical trial of Fibromyalgia Integrative Training (FIT teens) for adolescents with juvenile fibromyalgia - Study design and protocol.

OBJECTIVE: Juvenile-onset fibromyalgia (JFM) is a chronic debilitating pain condition that negatively impacts physical, social and academic functioning. Cognitive-behavioral therapy (CBT) is beneficial in reducing functional disability among adolescents with JFM but has only a modest impact on pain reduction and does not improve physical exercise participation. This randomized controlled trial (RCT) aims to test whether a novel intervention that combines CBT with specialized neuromuscular exercise training (the Fibromyalgia Integrative Training program for Teens "FIT Teens") is superior to CBT alone or a graded aerobic exercise (GAE) program. DESIGN/METHODS: This 3-arm multi-site RCT will examine the efficacy of the FIT Teens intervention in reducing functional disability (primary outcome) and pain intensity (secondary outcome), relative to CBT or GAE. All interventions are 8-weeks (16 sessions) in duration and are delivered in small groups of 4-6 adolescents with JFM. A total of 420 participants are anticipated to be enrolled across seven sites with approximately equal allocation to each treatment arm. Functional disability and average pain intensity in the past week will be assessed at baseline, post-treatment and at 3-, 6-, 9- and 12-month follow-up. The 3-month follow-up is the primary endpoint to evaluate treatment efficacy; longitudinal assessments will determine maintenance of treatment gains. Changes in coping, fear of movement, biomechanical changes and physical fitness will also be evaluated. CONCLUSIONS: This multi-site RCT is designed to evaluate whether the combined FIT Teens intervention will have significantly greater effects on disability and pain reduction than CBT or GAE alone for youth with JFM. Clinical trials.gov registration: NCT03268421.

Distinct interferon signatures and cytokine patterns define additional systemic autoinflammatory diseases.

BACKGROUNDUndifferentiated systemic autoinflammatory diseases (USAIDs) present diagnostic and therapeutic challenges. Chronic interferon (IFN) signaling and cytokine dysregulation may identify diseases with available targeted treatments.METHODSSixty-six consecutively referred USAID patients underwent underwent screening for the presence of an interferon signature using a standardized type-I IFN-response-gene score (IRG-S), cytokine profiling, and genetic evaluation by next-generation sequencing.RESULTSThirty-six USAID patients (55%) had elevated IRG-S. Neutrophilic panniculitis (40% vs. 0%), basal ganglia calcifications (46% vs. 0%), interstitial lung disease (47% vs. 5%), and myositis (60% vs. 10%) were more prevalent in patients with elevated IRG-S. Moderate IRG-S elevation and highly elevated serum IL-18 distinguished 8 patients with pulmonary alveolar proteinosis (PAP) and recurrent macrophage activation syndrome (MAS). Among patients with panniculitis and progressive cytopenias, 2 patients were compound heterozygous for potentially novel LRBA mutations, 4 patients harbored potentially novel splice variants in IKBKG (which encodes NF-κB essential modulator [NEMO]), and 6 patients had de novo frameshift mutations in SAMD9L. Of additional 12 patients with elevated IRG-S and CANDLE-, SAVI- or Aicardi-Goutières syndrome-like (AGS-like) phenotypes, 5 patients carried mutations in either SAMHD1, TREX1, PSMB8, or PSMG2. Two patients had anti-MDA5 autoantibody-positive juvenile dermatomyositis, and 7 could not be classified. Patients with LRBA, IKBKG, and SAMD9L mutations showed a pattern of IRG elevation that suggests prominent NF-κB activation different from the canonical interferonopathies CANDLE, SAVI, and AGS.CONCLUSIONSIn patients with elevated IRG-S, we identified characteristic clinical features and 3 additional autoinflammatory diseases: IL-18-mediated PAP and recurrent MAS (IL-18PAP-MAS), NEMO deleted exon 5-autoinflammatory syndrome (NEMO-NDAS), and SAMD9L-associated autoinflammatory disease (SAMD9L-SAAD). The IRG-S expands the diagnostic armamentarium in evaluating USAIDs and points to different pathways regulating IRG expression.TRIAL REGISTRATIONClinicalTrials.gov NCT02974595.FUNDINGThe Intramural Research Program of the NIH, NIAID, NIAMS, and the Clinical Center.

Musculoskeletal Pain, Physical Function, and Quality of Life After Bariatric Surgery.

OBJECTIVES: To evaluate the longitudinal effects of metabolic and bariatric surgery (MBS) on the prevalence of musculoskeletal and lower extremity (LE) pain, physical function, and health-related quality of life. METHODS: The Teen Longitudinal Assessment of Bariatric Surgery study (NCT00474318) prospectively collected data on 242 adolescents undergoing MBS at 5 centers over a 3-year follow-up. Joint pain and physical function outcomes were assessed by using the Health Assessment Questionnaire Disability Index, Impact of Weight on Quality of Life - Kids, and the Short Form 36 Health Survey. Adolescents with Blount disease (n = 9) were excluded. RESULTS: Prevalent musculoskeletal and LE pain were reduced by 40% within 12 months and persisted over 3 years. Adjusted models revealed a 6% lower odds of having musculoskeletal pain (odds ratio = 0.94, 95% confidence interval: 0.92-0.99) and a 10% lower odds of having LE pain (odds ratio = 0.90, 95% confidence interval: 0.86-0.95) per 10% reduction of BMI. The prevalence of poor physical function (Health Assessment Questionnaire Disability Index score >0) declined from 49% to <20% at 6 months (P < .05), Physical comfort and the physical component scores, measured by the Impact of Weight on Quality of Life - Kids and the Short Form 36 Health Survey, improved at 6 months postsurgery and beyond (P < .01). Poor physical function predicted persistent joint pain after MBS. CONCLUSIONS: Joint pain, impaired physical function, and impaired health-related quality of life significantly improve after MBS. These benefits in patient-reported outcomes support the use of MBS in adolescents with severe obesity and musculoskeletal pain and suggest that MBS in adolescence may reverse and reduce multiple risk factors for future joint disease.

General Nutrition and Fitness for the Child with Rheumatic Disease.

As a result of new medications and therapeutic approaches, most children with rheumatic diseases are no longer at risk for growth failure which results from chronic inflammation and prolonged corticosteroid treatment. However, obesity, poor nutrition, and insufficient exercise are still problems which increase risks for poor bone, cardiovascular, and general health. Diet should be monitored and modified as appropriate; supplemental calcium and Vitamin D should be provided. Obesity and poor physical fitness can be ameliorated by an exercise program that should become part of a more healthy lifestyle.

Relationships Between Standing Frontal-Plane Knee Alignment and Dynamic Knee Joint Loading During Walking and Jogging in Youth Who Are Obese.

BACKGROUND: Youth who are obese have high risk of poor knee health and cartilage damage. Understanding factors which may affect knee health in youth who are obese is critical for preservation of knee integrity and function. OBJECTIVE: This study compared standing frontal-plane knee alignment and knee loading patterns between youth who are obese and those of healthy weight and determine the association between knee alignment and knee loading patterns during walking and jogging. DESIGN: This study used a cross-sectional matched pair design. METHODS: Twenty youth who were obese and 20 youth who were healthy-weight (ages 11-18 years) were recruited. Three-dimensional motion analysis quantified standing frontal-plane knee alignment as well as frontal- and sagittal-plane knee moments during walking and jogging. Paired t -tests, multiple analysis of covariance, and Spearman's rank correlation coefficients were used for analysis. RESULTS: The youth who were obese demonstrated greater knee valgus in standing ( P  = 0.02), lower normalized peak external knee adduction moments during walking ( P  = 0.003), and greater normalized peak external knee extension moments during jogging ( P  = 0.003) compared with the youth who were healthy-weight. Standing knee alignment did not correlate with knee moments in the youth who were obese. LIMITATIONS: Results are limited to small, homogeneous cohorts. The standing alignment methodology is not validated in this population and may limit interpretation of results. CONCLUSION: Youth who are obese stand in more knee valgus and have altered knee loading patterns during walking and jogging compared with youth who are healthy-weight. Frontal-plane knee alignment does not correlate with frontal-plane knee loading patterns in youth who are obese. A better understanding of other mechanisms related to joint loading in youth who are obese is necessary to maintain long-term joint integrity in this population.

Muscle MRI at the time of questionable disease flares in Juvenile Dermatomyositis (JDM).

BACKGROUND: The course of JDM has improved substantially over the last 70 years with early and aggressive treatments. Yet it remains difficult to detect disease flares as symptoms may be mild; signs of rash and muscle weakness vary widely and are often equivocal; laboratory tests of muscle enzyme levels are often normal; electromyography and muscle biopsy are invasive. Alternative tools are needed to help decide if more aggressive treatment is needed. Our objective is to determine the effectiveness of muscle Magnetic Resonance Imaging (MRI) in detecting JDM flares, and how an MRI affects physician's decision-making regarding treatment. METHODS: This study was approved by the Institutional Review Board of Nationwide Children's Hospital. JDM patients were consulted between 1/2005 and 6/2015. MRIs were performed on both lower extremities without contrast sequentially: axial T1, axial T2 fat saturation, axial and coronal inversion recovery, and axial diffusion weighted. The physician decision that a JDM patient was in a flare was considered the gold standard. MRI results were compared with physician's decisions on whether a relapse had occurred, and if there was a concordance between the assessment methods. RESULTS: Forty-five JDM patients were studied. Eighty percent had weakness at diagnosis, 100% typical rash, and 73% typical nail-fold capillary changes. At diagnosis, muscle enzymes were compatible with JDM generally (CK 52%, LDH 62%, aldolase 72%, AST 54% abnormal). EMG was abnormal in 3/8, muscle biopsy typical of JDM in 10/11, and MRI abnormal demonstrating myositis in 31/40. Thirteen patients had a repeat MRI for possible flares with differing indications. Three repeat MRI's were abnormal, demonstrating myositis. There was moderate agreement about flares between MRI findings and physician's treatment decisions (kappa = 0.59). In each abnormal MRI case the physician decided to increase treatment (100% probability for flares). MRI was negative for myositis in 10 patients, by which 7/10 the physicians chose to continue or to taper the medications (70% probability for non-flares). CONCLUSION: A muscle MRI would facilitate objective assessments of JDM flares. When an MRI shows myositis, physicians tend to treat 100% of the time. When an MRI shows no myositis, physicians continued the same medications or tapered medications 70% of the time. Further studies would help confirm the utility and cost-effectiveness of MRI to determine JDM flares.

Changes in Functional Mobility and Musculoskeletal Pain After Bariatric Surgery in Teens With Severe Obesity: Teen-Longitudinal Assessment of Bariatric Surgery (LABS) Study.

IMPORTANCE: Severe obesity is associated with mobility limitations and higher incidence of multijoint musculoskeletal pain. It is unknown whether substantial weight loss improves these important outcomes in adolescents with severe obesity. OBJECTIVE: To examine the association of bariatric surgery with functional mobility and musculoskeletal pain in adolescents with severe obesity up to 2 years after surgery. DESIGN, SETTING, AND PARTICIPANTS: The Teen-Longitudinal Assessment of Bariatric Surgery Study is a prospective, multicenter, observational study, which enrolled 242 adolescents (≤19 years of age) who were undergoing bariatric surgery from March 2007 through February 2012 at 5 US adolescent bariatric surgery centers. This analysis was conducted in November 2015. INTERVENTIONS: Roux-en-Y gastric bypass (n = 161), sleeve gastrectomy (n = 67), or laparoscopic adjustable gastric band (n = 14). MAIN OUTCOMES AND MEASURES: Participants completed a 400-m walk test prior to bariatric surgery (n = 206) and at 6 months (n = 195), 12 months (n = 176), and 24 months (n = 149) after surgery. Time to completion, resting heart rate (HR), immediate posttest HR, and HR difference (resting HR minus posttest HR) were measured and musculoskeletal pain concerns, during and after the test, were documented. Data were adjusted for age, sex, race/ethnicity, baseline body mass index (calculated as weight in kilograms divided by height in meters squared), and surgical center (posttest HR and HR difference were further adjusted for changes in time to completion). RESULTS: Of the 206 adolescents with severe obesity included in the study, 156 were female (75.7%), the mean (SD) age was 17.1 (1.6) years, and the mean (SD) body mass index was 51.7 (8.5). Compared with baseline, significant improvements were observed at 6 months for the walk test time to completion (mean, 376 seconds; 95% CI, 365-388 to 347 seconds; 95% CI, 340-358; P < .01), resting HR (mean, 84 beats per minute [bpm]; 95% CI, 82-86 to 74 bpm; 95% CI, 72-76), posttest HR (mean, 128 bpm; 95% CI, 125-131 to 113 bpm; 95% CI, 110-116), and HR difference (mean, 40 bpm; 95% CI, 36-42 to 34 bpm; 95% CI, 31-37). These changes in time to completion, resting HR, and HR difference persisted at 12 months and 24 months. Posttest HR further improved from 6 months to 12 months (mean, 113 bpm; 95% CI, 110-116 to 108 bpm; 95% CI, 105-111). There were statistically significant reductions in musculoskeletal pain concerns at all points. CONCLUSIONS AND RELEVANCE: These data provide evidence that bariatric surgery in adolescents with severe obesity is associated with significant improvement in functional mobility and in the reduction of walking-related musculoskeletal pain up to 2 years after surgery.

Utility of Neurodiagnostic Studies in the Diagnosis of Autoimmune Encephalitis in Children.

BACKGROUND: Autoimmune encephalitis is currently a clinical diagnosis without widely accepted diagnostic criteria, often leading to a delay in diagnosis. The utility of magnetic resonance imaging (MRI) and electroencephalography (EEG) in this disease is unknown. The objective of this study was to identify disease-specific patterns of neurodiagnostic studies (MRI and EEG) for autoimmune encephalitis in children. METHODS: We completed a retrospective chart review of encephalopathic patients seen at a large pediatric hospital over a four year interval. Clinical presentation, autoantibody status, and MRI and EEG findings were identified and compared. Individuals with autoantibodies were considered "definite" cases, whereas those without antibodies or those with only thyroperoxidase antibodies were characterized as "suspected." RESULTS: Eighteen patients met the inclusion criteria and autoantibodies were identified in nine of these. The patients with definite autoimmune encephalitis had MRI abnormalities within limbic structures, most notably the anteromedial temporal lobes (56%). Only individuals with suspected disease had nontemporal lobe cortical lesions. Sixteen patients had an EEG and 13 (81%) of these were abnormal. The most common findings were abnormal background rhythm (63%), generalized slowing (50%), focal slowing (43%), and focal epileptiform discharges (31%). Sleep spindle abnormalities occurred in 38% of patients. There were no specific differences in the EEG findings between the definite and suspected cases. Focal EEG findings only correlated with a focal lesion on MRI in a single definite case. CONCLUSIONS: Pediatric patients with definite autoimmune encephalitis have a narrow spectrum of MRI abnormalities. Conversely, EEG abnormalities are mostly nonspecific. All patients in our cohort had abnormalities on one or both of these neurodiagnostic studies.

Cardiovascular risk and metabolic syndrome in obese youth enrolled in a multidisciplinary medical weight management program: implications of musculoskeletal pain, cardiorespiratory fitness, and health-related quality of life.

BACKGROUND: Obese youth demonstrate the same obesity-associated morbidities observed in obese adults, including poor cardiorespiratory fitness, poor quality of life, and reports of musculoskeletal pain. The purposes of this study were to compare the prevalence of cardiovascular risk factors and evaluate the odds of metabolic syndrome in obese youth based on measures of cardiorespiratory fitness, quality of life, and pain. METHODS: A medical chart review of 183 obese youth in a medical weight management program was conducted. Measures of cardiovascular risk and metabolic syndrome were recorded. Groups were categorized based on Progressive Aerobic Cardiovascular Endurance Run (PACER) score, Pediatric Quality of Life (PedsQL)-Physical Function score, PedsQL-Psychosocial Health score, and reports of musculoskeletal pain. Statistical analysis included independent t-tests, Mann-Whitney U-test, chi-squared test, and logistic regression. RESULTS: Thirty-three percent of the entire sample had C-reactive protein (CRP) levels >3.0 mg/dL and 30% were categorized as having metabolic syndrome. Patients with lower PACER scores demonstrated a greater prevalence of CRP levels >3.0 mg/dL versus those with higher PACER scores (45% vs. 12%; P=0.01). There were no other differences in the prevalence of cardiovascular risk factors or metabolic syndrome when categorized by PACER, PedsQL, or pain. Those with CRP levels >3.0 mg/dL demonstrated increased odds of metabolic syndrome-[odds (95% confidence interval, CI): 4.93 (1.24-19.61); P=0.02]. CONCLUSIONS: Overall, results do not show differences in cardiovascular risk in obese youth when categorized by PACER, PedsQL, or reports of MSK pain. Elevated CRP may be a useful predictor of metabolic syndrome in obese youth and warrants further investigation.

Obesity is associated with greater valgus knee alignment in pubertal children, and higher body mass index is associated with greater variability in knee alignment in girls.

OBJECTIVE: In adults, osteoarthritis (OA) is associated with obesity and knee alignment. Whether knee alignment differences develop during childhood and are associated with obesity is unknown. We assessed the distribution of knee alignment in children and adolescents, and determined how knee alignment differs between obese and nonobese children. METHODS: This cross-sectional study examined knee alignment in 155 healthy weight and 165 obese subjects. Knee alignment [metaphyseal-diaphyseal angle (MDA) and anterior tibiofemoral angle (ATFA)] and fat mass were measured using whole body dual-energy X-ray absorptiometry (DEXA). National reference data were used to generate age- and sex-specific body mass index (BMI, kg/m(2)) Z-scores. Multivariable linear regression was used to identify independent factors associated with ATFA and MDA. RESULTS: The mean MDA and ATFA were similar between obese and nonobese subjects. In stratified analyses, females had greater variability in MDA and ATFA values (p < 0.001 and p = 0.04, respectively) at higher BMI Z-scores. Compared with healthy weight controls, obese subjects had less valgus of the MDA prior to the onset of puberty (+ 2.0°, p = 0.001), but had greater valgus at later pubertal stages (-1.9°, p = 0.01). CONCLUSION: We found significantly greater variability in knee alignment among females at higher BMI Z-scores, and greater valgus alignment in obese adolescents in late puberty. The major limitation is the use of DEXA for assessment of alignment, which needs validation against longstanding radiographs. Longitudinal studies are needed to determine whether childhood obesity is a risk factor for progressive malalignment that may predispose to pain and risk of early osteoarthritis.