Bone marrow fat content in 70 adolescent girls with anorexia nervosa: Magnetic resonance imaging and magnetic resonance spectroscopy assessment.

BACKGROUND: Adolescents and women with anorexia nervosa have increased bone marrow fat and decreased bone formation, at least in part due to hormonal changes leading to preferential stem cell differentiation to adipocytes over osteoblasts. OBJECTIVE: The purpose of this study was to evaluate marrow fat content and correlate with age and disease severity using knee MRI with T1 relaxometry (T1-R) and MR spectroscopy (MRS) in 70 adolescents with anorexia nervosa. MATERIALS AND METHODS: We enrolled 70 girls with anorexia nervosa who underwent 3-T knee MRI with coronal T1-W images, T1-R and single-voxel proton MRS at 30 and 60 ms TE. Metaphyses were scored visually on the T1-W images for red marrow. Visual T1 score, T1 relaxometry values, MRS lipid indices and fat fractions were analyzed by regression on age, body mass index (BMI) and bone mineral density (BMD) as disease severity markers. MRS measures included unsaturated fat index, T2 water, unsaturated and saturated fat fractions. RESULTS: All red marrow measures declined significantly with age. T1-R values were associated negatively with BMI and BMD for girls ≤16 years (P=0.03 and P=0.002, respectively) and positively for those≥17 years (P=0.05 and P=0.003, respectively). MRS identified a strong inverse association between T2 water and saturated fat fraction from 60 ms TE data (r=-0.85, P<0.0001). There was no association between unsaturated fat index and BMI or BMD. CONCLUSIONS: The association between T1 and BMI and BMD among older girls suggests more marrow fat in those with severe anorexia nervosa. In contrast, the physiological association between marrow fat content and age remained dominant in younger patients. The strong association between T2 water and saturated fat may relate to the restricted mobility of water with increasing marrow fat.

Association between opioid utilization and patient-reported outcome measures following lumbar spine surgery.

BACKGROUND CONTEXT: The patient-reported outcomes measurement information system (PROMIS), created by the National institute of Health, is a reliable and valid survey for patients with lumbar spine pathology. Preoperative opioid use has been shown to be an important predictor variable of self-reported health status in legacy patient-reported outcome measures. PURPOSE: To investigate the impact of chronic preoperative opiate use on PROMIS survey scores. STUDY DESIGN: Retrospective database analysis. PATIENT SAMPLE: Between March 2019 and November 2021, 227 patients underwent lumbar decompression ± ≤ 2 level fusion. Fifty-seven patients (25.11%) had chronic preoperative opioid use. OUTCOME MEASURES: Oswestry disability index (ODI) and PROMIS survey scores. METHODS: A retrospective analysis of a prospectively maintained single center patient-reported outcome database was performed with a minimum of 2 year follow-up. PROMIS Anxiety, Depression, Fatigue, Pain Interference (PI), Physical Function (PF), Sleep disturbance (SD), and Social Roles (SR) surveys were recorded at preoperative intake with subsequent follow-up at 6, 12, and 24 months postoperatively. Patients were grouped into chronic opioid users as defined by >6-month duration of use. Differences in mean survey scores were evaluated using Welch t-tests. RESULTS: Two hundred and twenty-seven patients met our inclusion criteria of completed PROMIS surveys at the designated timepoints. A total of 57 (25.11%) were chronic opioid users (COU) prior to surgery. Analysis of patient-reported health outcomes shows that long term opioid use correlated with worse ODI and PROMIS scores at baseline compared to nonchronic users (NOU). At 1 and 2 year follow-up, the COU cohort continued to have significantly worse ODI, PROMIS Fatigue, PF, PI, SD, and SR scores. There is a statistical difference in the magnitude of change in health status between the 2 cohorts at 1 year follow-up in PROMIS Depression (-5.04±7.88 vs -2.49±8.73, p=.042), PF (6.25±7.11 vs 9.03±9.04, p=.019), and PI (-7.40±7.37 vs -10.58±9.87, p=.011) and 2 year follow-up in PROMIS PF (5.58±6.84 vs 7.99±9.64, p=.041) and PI (-6.71±8.32 vs -9.62±10.06, p=.032). Mean improvement in PROMIS scores for the COU cohort at 2 year follow-up exceeded minimal clinically important difference (MCID) in all domains except PROMIS Depression, SR and SD. CONCLUSION: Patients with chronic opioid use status have worse baseline PROMIS scores compared with patients who had nonchronic use. However, patients in the COU cohort displayed clinically significant postoperative improvement in multiple PROMIS domains. These results show that patients with chronic opioid use can benefit greatly from surgical intervention and will allow physicians to better set expectations with their patients.

Reversible addition-fragmentation chain transfer polymerization in microemulsion.

This tutorial review first details the uncontrolled microemulsion polymerization mechanism, and the RAFT polymerization mechanism to provide the necessary background for examining the RAFT microemulsion polymerization mechanism. The effect of the chain transfer agent per micelle ratio and the chain transfer agent aqueous solubility on the RAFT microemulsion polymerization kinetics, polymer molecular weight and polydispersity, and polymer nanoparticle size are discussed with a focus on oil-in-water microemulsions. Modeling of RAFT microemulsion polymerization kinetics and the resulting final polymer molecular weight are presented to assist with the analysis of observed experimental trends. Lastly, the current significance of RAFT microemulsion polymerization and the future directions are discussed.

Scheuermann Kyphosis: Current Concepts and Management.

PURPOSE OF REVIEW: Scheuermann's kyphosis (SK) is a developmental deformity of the spine that affects up to 8% of children in the US. Although, the natural progression of SK is noted to be gradual over years, severe deformity can be associated with significant morbidity. Thorough clinical examination and interpretation of relevant imaging help differentiate and confirm this diagnosis. Treatment includes both operative and nonoperative approaches. The purpose of this article is to provide an updated overview of the current theories of its pathogenesis, as well as the principles of diagnosis and treatment of SK. RECENT FINDINGS: Although a definitive, unified theory continues to be elusive, numerous reports in the past decade provide insight into the pathophysiology of SK. These include alterations in mechanical stress and/or hormonal disturbances. Candidate genes have also been identified to be linked to the inheritance of SK. Updates to nonoperative treatment include the effectiveness of dedicated exercise programs, as well as the types and duration of orthotic treatment. Advances in surgical technique can be observed with a trend toward a posterior-only approach, with supporting evidence for careful evaluation of both the sagittal and coronal planes to determine fusion levels in order to avoid postoperative junctional pathologies. SK is an important cause of structural or rigid kyphosis. It can lead to significant morbidity in severe cases. Treatment is based on curve magnitude and symptoms. Nonoperative treatment consists of physical therapy in symptomatic patients, and bracing can be added for skeletally mature patients. Operative management can be considered in patients with large, progressive, and symptomatic deformity. Future studies can benefit from a focused investigation into patient-reported outcomes after undergoing appropriate treatment.

Anterior vertebral body tethering for adolescent idiopathic scoliosis associated with less early post-operative pain and shorter recovery compared with fusion.

PURPOSE: While posterior spinal instrumentation and fusion (PSIF) for severe adolescent idiopathic scoliosis (AIS) is the gold standard, anterior vertebral body tethering (AVBT) is becoming an alternative for select cases. Several studies have compared technical outcomes for these two procedures, but no studies have compared post-operative pain and recovery. METHODS: In this prospective cohort, we evaluated patients who underwent AVBT or PSIF for AIS for a period of 6 weeks after operation. Pre-operative curve data were obtained from the medical record. Post-operative pain and recovery were evaluated with pain scores, pain confidence scores, PROMIS scores for pain behavior, interference, and mobility, and functional milestones of opiate use, independence in activities of daily living (ADLs), and sleeping. RESULTS: The cohort included 9 patients who underwent AVBT and 22 who underwent PSIF, with a mean age of 13.7 years, 90% girls, and 77.4% white. The AVBT patients were younger (p = 0.03) and had fewer instrumented levels (p = 0.03). Results were significant for decreased pain scores at 2 and 6 weeks after operation (p = 0.004, and 0.030), decreased PROMIS pain behavior at all time points (p = 0.024, 0.049, and 0.001), decreased pain interference at 2 and 6 weeks post-operative (p = 0.012 and 0.009), increased PROMIS mobility scores at all time points (p = 0.036, 0.038, and 0.018), and faster time to functional milestones of weaning opiates, independence in ADLs, and sleep (p = 0.024, 0.049, and 0.001). CONCLUSION: In this prospective cohort study, the early recovery period following AVBT for AIS is characterized by less pain, increased mobility, and faster recovery of functional milestones, compared with PSIF. LEVEL OF EVIDENCE: IV.

Impact of social determinants of health on perioperative opioid utilization in patients with lumbar degeneration.

Background: Social determinants of health (SDOH), have been demonstrated to significantly impact health outcomes in spine patients. There may be interaction between opioid use and these factors in spine surgical patients. We aimed to evaluate the social determinants of health (SDOH) which are associated with perioperative opioid use among lumbar spine patients. Methods: This retrospective cohort study included patients undergoing spine surgery for lumbar degeneration in 2019. Opioid use was determined based on prescription records from the electronic medical records. Preoperative opioid users (OU) were compared with opioid-naïve patients regarding SDOH including demographics like age and race, and clinical data such as activity and tobacco use. Demographics and surgical data, including age, comorbidities, surgical invasiveness, and other variables were also collected from the records. Multivariate logistic regression was used for analysis of these factors. Results: Ninety-eight patients were opioid-naïve and 90 used opioids preoperatively. All OU had ≥3 months of use, had more prior spine surgeries (1.07 vs. 0.44, p<.001) and more comorbidities including diabetes, hypertension, and depression (p=.021, 0.043, 0.017). Patients from lower community median income areas, unemployed, or with lower physical capacity (METS<5) were more likely to use opioids preoperatively. Postoperative opioid use was strongly associated with preoperative opioid use, as well as alcohol use, and lower community median income. At one year postoperatively, OU had higher rates of opioid use [72.2% vs. 15.3%, p<.001]. Conclusions: Unemployment, low physical activity level, and lower community median income were associated with preoperative opioid use and longer-term opioid use postoperatively.

Surgical Correction of Neuromuscular Scoliosis Secondary to Congenital Zika Syndrome: A Case Report.

CASE: Congenital Zika syndrome (CZS) has been noted after the South American pandemic of Zika virus which peaked in 2015 to 2016, and the associated sequelae are still being described. Scoliosis has been noted in patients with CZS; however, there is a paucity of literature on the prevalence or management of scoliosis secondary to this condition. We report the case of a 5-year-old girl with severe neuromuscular scoliosis due to CZS that was managed with halo-gravity traction, followed by a growth-friendly construct. CONCLUSION: This case report highlights the need for more research focusing on the survivors of the Zika pandemic.

Diagnosis and Management of Osteomyelitis in Children: A Critical Analysis Review.

The most common causative organism of pediatric osteomyelitis is Staphylococcus aureus, although, more recently, organisms such as Kingella kingae and methicillin-resistant S. aureus have been increasing in prevalence. Magnetic resonance imaging is the best diagnostic imaging modality for pediatric osteomyelitis given its high sensitivity and specificity. Most cases of early osteomyelitis without a drainable abscess can be adequately treated with a short course of intravenous antibiotics followed by at least 3 weeks of oral antibiotics. Surgical management of pediatric osteomyelitis is usually indicated in the presence of an abscess and/or failed treatment with antibiotic therapy. Clinical examination, fever, and C-reactive protein testing should be used to guide the conversion to oral antibiotics, the total antibiotic regimen duration, and the need for an additional debridement surgical procedure.

Correlation of Functional Magnetic Resonance Imaging Response to Visual Food Stimuli With Clinical Measures in Adolescents With Restrictive Eating Disorders.

PURPOSE: Previous reports have shown limbic dysregulation in patients with restrictive eating disorders (EDs). This study investigated functional responses in brain systems to visual food stimuli and their correlation with psychological and behavioral outcomes. METHODS: A total of 18 females, aged 13-18 years, who were diagnosed with anorexia nervosa (n = 11) or atypical anorexia nervosa (n = 7), completed functional magnetic resonance imaging during a visual food paradigm. Stimuli included four food types and one nonfood. Anxiety and disordered eating cognitions were assessed using the State-Trait Anxiety Inventory and Eating Attitude Test (EAT-26). Analyses were performed to obtain contrasts among different food categories and test their correlations with cognitive and behavioral scores. RESULTS: Contrasts of foods versus nonfood generally resulted in positive responses in occipital regions and negative responses in temporal and parietal gyri. Contrast of sweets versus nonfood, in particular, elicited additional activation in the hippocampus. Contrasting sweet to nonsweet food, the orbitofrontal cortex and anterior cingulate cortex (ACC) were activated. Contrast of all foods versus nonfood had a positive correlation with State-Trait Anxiety Inventory-state scores in the orbitofrontal cortex and ACC. Finally, the sweet versus nonsweet contrast correlated positively with EAT-26 in ACC and other frontal areas. CONCLUSIONS: Visual food stimuli elicited brain responses in limbic centers, and sweet foods extended activation to other limbic domains. Sweet food contrast correlated to EAT-26 in regions comprising the default mode network tied to introspection. Thus, we conclude that visual food stimuli produce activation in limbic-regulating regions in patients with restrictive EDs that correlate with disordered-eating cognitions and behaviors.

Impact of Adrenal Hormone Supplementation on Bone Geometry in Growing Teens With Anorexia Nervosa.

PURPOSE: Adolescents with anorexia nervosa (AN) have decreased dehydroepiandrosterone (DHEA) and estrogen concentrations that may contribute to skeletal deficits. We sought to determine whether DHEA + estrogen replacement (ERT) prevented bone loss in young adolescents with AN. METHODS: We recruited females with AN (n = 70, ages 11-18 years) into a 12-month, randomized, double-blind placebo-controlled trial. Participants were randomized to oral micronized DHEA 50 mg + 20 mcg ethinyl estradiol/.1 mg levonorgestrel daily (n = 35) or placebo (n = 35). Outcomes included serial measures of bone mineral density (BMD) by dual-energy X-ray absorptiometry (total body, hip, spine) and peripheral quantitative computed tomography (pQCT; tibia). Magnetic resonance imaging of T1-weighted images of the left knee determined physeal status (open/closed). RESULTS: Sixty-two subjects completed the trial. Physeal closure status was the strongest predictor of aBMD changes. Among girls with open physes, those who received DHEA + ERT showed a decline in BMD Z-scores compared with those receiving placebo, whereas there was no effect in those with at least one closed physis. Treatment did not affect any pQCT measures, regardless of physeal closure status. CONCLUSIONS: Combined DHEA + ERT did not significantly improve dual-energy X-ray absorptiometry or pQCT BMD measurements in young adolescent girls with AN, in contrast to an earlier trial showing benefit in older adolescents and young women. In girls with open physes, the mean change in the placebo arm was greater than that of the DHEA + ERT group. We conclude that DHEA + ERT is ineffective for preserving bone health in growing young adolescents with AN at the dose and route of administration described in this report.

Magnetic resonance imaging and spectroscopy evidence of efficacy for adrenal and gonadal hormone replacement therapy in anorexia nervosa.

PURPOSE: Dehydroepiandrosterone (DHEA)+estrogen/progestin therapy for adolescent girls with anorexia nervosa (AN) has the potential to arrest bone loss. The primary aim of this study was to test the effects of DHEA+estrogen/progestin therapy in adolescent girls with AN on bone marrow in the distal femur using magnetic resonance imaging (MRI) and spectroscopy. METHODS: Seventy adolescent girls with AN were enrolled in a double blind, randomized, placebo-controlled trial at two urban hospital-based programs. INTERVENTION: Seventy-six girls were randomly assigned to receive 12months of either oral micronized DHEA or placebo. DHEA was administered with conjugated equine estrogens (0.3mg daily) for 3months, then an oral contraceptive (20µg ethinyl estradiol/ 0.1mg levonorgestrel) for 9months. The primary outcome measure was bone marrow fat by MRI and magnetic resonance spectroscopy (MRS). RESULTS: T2 of the water resonance dropped significantly less in the active vs. placebo group over 12months at both the medial and lateral distal femur (p=0.02). Body mass index (BMI) was a significant effect modifier for T1 and for T2 of unsaturated (T2unsat) and saturated fat (T2sat) in the lateral distal femur. Positive effects of the treatment of DHEA+estrogen/progestin were seen primarily for girls above a BMI of about 18kg/m2. CONCLUSIONS: These findings suggest treatment with oral DHEA+estrogen/progestin arrests the age- and disease-related changes in marrow fat composition in the lateral distal femur reported previously in this population.

Use of dual energy X-ray absorptiometry in pediatric patients.

Dual Energy X-ray Absorptiometry (DXA) is a vital tool for assessing bone health in patients at risk for fragility fractures. In pediatric patients, this technology is used in conjunction with clinical fracture history to diagnosis osteoporosis and monitor treatment response. Childhood and adolescence is characterized by linear growth and bone mass accrual; thus there are important differences in the interpretation of bone measurements obtained by DXA in these young patients. This review aims to explore the current indications for DXA use and interpretation of DXA in the pediatric age group using currently available reference databases. Limitations of DXA in pediatric patients, specifically in children with short stature, will be explored. We will review several pathophysiologic mechanisms that may lead to low bone density in children, discussing representative diseases and the recommendations for monitoring bone health with DXA in these conditions. Finally, we will highlight new methods by which DXA imaging can gather additional information on bone health in children and may improve our ability to predict fractures and osteoporosis.

Effect of Exercise and Antidepressants on Skeletal Outcomes in Adolescent Girls With Anorexia Nervosa.

PURPOSE: We examined the relationships between malnutrition, lifestyle factors, and bone health in anorexia nervosa (AN) via dual-energy X-ray absorptiometry (DXA) and peripheral quantitative computed tomography (pQCT). METHODS: Seventy adolescent girls with AN and 132 normal-weighted controls underwent pQCT tibial measures including trabecular volumetric bone mineral density (vBMD), cortical vBMD, and cortical thickness. Participants with AN underwent DXA measures of the axial skeleton. We assessed the association of DXA and pQCT measures with clinical and lifestyle variables. RESULTS: Body mass index Z-score and ideal body weight percentage were positively correlated with trabecular vBMD, cortical CSA, and section modulus (p < .04). Exercise was associated with all pQCT measures but only with hip BMD by DXA. In AN, the use of antidepressants was associated with lower pQCT measures (p < .03). CONCLUSIONS: Antidepressants may negatively, and exercise positively, influence BMD in adolescents with eating disorders. These findings offer a provocative look at two longstanding questions.

Spinal Bone Texture Assessed by Trabecular Bone Score in Adolescent Girls With Anorexia Nervosa.

CONTEXT: Trabecular bone score (TBS) is a bone assessment tool that offers information beyond that afforded by dual-energy x-ray absorptiometry (DXA) bone mineral density (BMD) measurements. Adolescents with anorexia nervosa (AN) are known to exhibit compromised bone density and skeletal strength. OBJECTIVES: This study aimed to determine TBS among adolescents with AN and evaluate the correlation with anthropometric, clinical and densitometric variables. DESIGN: Areal BMD spinal measures were analyzed for TBS. Findings were compared with clinical (height, weight, body mass index [BMI], age, pubertal development, 25-hydroxyvitamin D) and self-reported data (illness duration, amenorrhea, exercise, fracture, family history of osteoporosis, and antidepressant use), and BMD measures by DXA and peripheral quantitative computed tomography (pQCT). SETTING AND PARTICIPANTS: This was an urban adolescent program consisting of 57 females with AN, age 11-18 y. INTERVENTIONS: Interventions included DXA (absolute BMD and Z-score), pQCT (volumetric BMD [vBMD] and stress-strain index [SSI]), laboratory evaluation, and questionnaire administration. MAIN OUTCOME MEASURES: Main outcome measures included TBS, areal and vBMD, SSI, fracture history, disease duration. RESULTS: The TBS of six participants (11%) showed degraded and 19 (33%) partially degraded microarchitecture. Spinal TBS was correlated (P < .05) with age, height, weight, BMI, pubertal stage, BMD, and body composition by DXA, and BMD and SSI by pQCT. TBS was not correlated with disease duration, fracture, vitamin D status, race, or ethnicity, and self-reported health data. CONCLUSIONS: TBS showed evidence of degraded microarchitecture in over 40% of this study sample, and strongly correlated with anthropometric data and measures of BMD and skeletal strength. TBS is a novel tool that captures another dimension of bone health in adolescents with AN.

Risk taking differences on a behavioral task as a function of potential reward/loss magnitude and individual differences in impulsivity and sensation seeking.

Although previous studies have shown that the Balloon Analogue Risk Task (BART; [Lejuez, C.W., Read, J.P., Kahler, C.W., Richards, J.B., Ramsey, S.E., Stuart, G.L., et al. (2002). Evaluation of a Behavioral Measure of Risk Taking: The Balloon Analogue Risk Test (BART). J Exp Psychol, Appl, 8, 75-84.; Lejuez, C., Aklin, W., Jones, H., Richards, J., Strong, D., Kahler, C.W., et al. (2003a). The Balloon Analogue Risk Task (BART) Differentiates Smokers and Nonsmokers. Exp Clin Psychopharmacol, 11, 26-33.; Lejuez, C., Aklin, W., Zvolensky, M., & Pedulla, C. (2003b). Evaluation of the Balloon Analogue Risk Task (BART) as a Predictor of Adolescent Real-world Risk-taking Behaviors. J Adolesc, 26, 475-479.]) can be used to index real-world risk-taking behavior, questions remain regarding how performance on the task may vary as a function of reward/loss value and how this relationship may differ as a function of relevant personality traits. The present study examined BART score at 1, 5, and 25 cents per pump and how this relationship differed at low and high levels of impulsivity and sensation seeking. Results indicated that riskiness on the BART decreased as reward/loss magnitude increased. Further, this decrease was most prominent in those low in Impulsivity/Sensation Seeking, whereas those high in Impulsivity/Sensation Seeking were largely insensitive to variation in reward/loss magnitude. Findings are discussed in terms of sensitivity to reward and loss, and how these processes can be studied further using the BART including extensions to cognitive modeling and the measurement of neurobehavioral functioning.