Survival outcomes in pediatric patients with metastatic Ewing sarcoma who achieve a rapid complete response of pulmonary metastases.

PURPOSE: Our objectives were to compare overall survival (OS) and pulmonary relapse between patients with metastatic Ewing sarcoma (EWS) at diagnosis who achieve rapid complete response (RCR) and those with residual pulmonary nodules after induction chemotherapy (non-RCR). PATIENTS AND METHODS: This retrospective cohort study included children under 20 years with metastatic EWS treated from 2007 to 2020 at 19 institutions in the Pediatric Surgical Oncology Research Collaborative. Chi-square tests were conducted for differences among groups. Kaplan-Meier curves were generated for OS and pulmonary relapse. RESULTS: Among 148 patients with metastatic EWS at diagnosis, 61 (41.2%) achieved RCR. Five-year OS was 71.2% for patients who achieved RCR, and 50.2% for those without RCR (p = .04), and in multivariable regression among patients with isolated pulmonary metastases, RCR (hazards ratio [HR] 0.42; 95% confidence interval [CI]: 0.17-0.99) and whole lung irradiation (WLI) (HR 0.35; 95% CI: 0.16-0.77) were associated with improved survival. Pulmonary relapse occurred in 57 (37%) patients, including 18 (29%) in the RCR and 36 (41%) in the non-RCR groups (p = .14). Five-year pulmonary relapse rates did not significantly differ based on RCR (33.0%) versus non-RCR (47.0%, p = .13), or WLI (38.8%) versus no WLI (46.0%, p = .32). DISCUSSION: Patients with EWS who had isolated pulmonary metastases at diagnosis had improved OS if they achieved RCR and received WLI, despite having no significant differences in rates of pulmonary relapse.

Baseline Serum Biomarkers of Inflammation and Subsequent Visit-to-Visit Blood Pressure Variability: A Post Hoc Analysis of MESA.

BACKGROUND: Higher blood pressure variability (BPV) is associated with the development of major vascular diseases, independent of mean blood pressure. However, despite data indicating that serum inflammatory markers are linked to hypertension, the association between serum inflammatory markers and BPV has not been studied in humans. METHODS: This is a post hoc analysis of the Multi-Ethnic Study of Atherosclerosis (MESA) study. The study exposure was tertiles of serum level of interleukin-6 (IL-6), C-reactive protein (CRP), d-dimer, plasmin-antiplasmin complex (PAP), fibrinogen antigen, and calibrated Factor VIII (%) at the baseline study visit. The primary outcome was visit-to-visit BPV measured as the residual standard deviation (rSD) of at least 4 study visits (2000-2018). Two logistic regression models were fit to the top tertile of rSD during follow-up: in Model 1, we adjusted for age, sex, and hypertension, and in Model 2, for patient age categories, sex, race/ethnicity, education, hypertension, diabetes, smoking, drinking, body mass index, lipid-lowering medication, and mean systolic blood pressure. RESULTS: Our analysis included 5,483 patients, with a mean (SD) age of 61.4 (10.0) years, 52.9% female, and 40.7% White. In unadjusted analyses, all markers of inflammation were associated with higher BPV, but after adjustment, only IL-6 retained significance (P < 0.001). The odds ratio for the highest tertile of BPV and IL-6 was 1.49 (95% confidence interval [CI] 1.28-1.74, P < 0.001). CONCLUSIONS: Baseline serum IL-6 was associated with increased subsequent BPV in a large multiracial cohort. Further investigation is needed to better understand the relationship between chronic inflammation and BPV.

Diagnostic Test Characteristics of Ultrasound Based Hydronephrosis in Identifying Low Kidney Function in Young Patients with Spina Bifida: A Retrospective Cohort Study.

PURPOSE: Kidney dysfunction in spina bifida is usually detected by low estimated glomerular filtration rate or ultrasound based hydronephrosis. We assessed the diagnostic test characteristics of hydronephrosis for detecting low estimated glomerular filtration rate, hypothesizing that hydronephrosis has low sensitivity compared to cystatin C based estimated glomerular filtration rate. MATERIALS AND METHODS: We conducted a single center, retrospective cohort study, including patients with spina bifida from 2012-2017 with 2 kidneys and complete data needed to calculate estimated glomerular filtration rate via multiple pediatric (age 1-17.9 years) or adult (age ≥18 years) estimating equations. We evaluated the association of hydronephrosis status (high grade, low grade or none) with estimated glomerular filtration rate, adjusting for small kidney size and scarring, and calculated diagnostic test characteristics of hydronephrosis for low estimated glomerular filtration rate. RESULTS: We analyzed 247 patients (176 children and 71 adults). Mean±SD age was 13.7±6.6 years, and 81% of patients had myelomeningocele. Hydronephrosis (77% low grade) was found in 35/176 children and 18/71 adults. Hydronephrosis was associated with low estimated glomerular filtration rate in stepwise fashion, independent of kidney size and scarring. However, across cystatin C based pediatric equations, any hydronephrosis (compared to none) had 23%-48% sensitivity, and high grade hydronephrosis (compared to none or low grade) had 4%-15% sensitivity for estimated glomerular filtration rate <90 ml/min/1.73 m2, which remained unchanged after excluding small kidneys and scarring. Across cystatin C based adult equations, any and high grade hydronephrosis had 55%-75% and 40%-100% sensitivity, respectively, for estimated glomerular filtration rate <90 ml/min/1.73 m2, although with wide confidence intervals. Specificity was higher with high grade vs any hydronephrosis. Sensitivities were higher for estimated glomerular filtration rate <60 ml/min/1.73 m2. CONCLUSIONS: Hydronephrosis was associated with low estimated glomerular filtration rate but had poor sensitivity for cystatin C based estimated glomerular filtration rate <90 ml/min/1.73 m2, especially among children with spina bifida.

Estimated kidney function in children and young adults with spina bifida: A retrospective cohort study.

AIMS: Current estimated glomerular filtration rate (eGFR) equations may be inaccurate in patients with spina bifida (SB) because of reduced muscle mass and stature. Cross-sectional and longitudinal variability of eGFR were analyzed in these patients across multiple equations, hypothesizing greater variability in creatinine-based than cystatin-C (Cys-C)-based equations. METHODS: This retrospective cohort study included children (age, 1-17.9 years) and adults (≥18 years) with SB from 2002-2017 at a large SB clinic. Those without all data needed to calculate eGFR were excluded. Four pediatric and three adult eGFR equations were compared for cross-sectional outcomes of eGFR and elevated office blood pressures using chronic kidney disease (CKD) stage classification, and for longitudinal outcome of eGFR slope over time using covariance pattern models accounting for repeated measures. RESULTS: One hundred and eighty two children and 75 adults had greater than or equal to 1 set of data measurements; 118 and 52, respectively, had greater than or equal to 2 sets. The pediatric bedside Schwartz equation had the highest median eGFR and coefficient of variation. CKD stage classification by eGFR showed large differences across equations in children, with rates of eGFR < 60 and <90 ml/min/1.73 m2 ranging from 2%-9% and 5%-69%, respectively. Only one equation showed a significant inverse association between eGFR and blood pressure. Longitudinally, eGFR slopes over time were different across pediatric equations (P < .001) but not adult equations. The bedside Schwartz equation had a positive eGFR slope; the other Cys-C-containing equations had negative slopes. CONCLUSIONS: Creatinine-based equations in children with SB vary considerably from cystatin-C-containing equations in calculating both single point-in-time eGFR values and eGFR trends over time.

Gray Matter Correlates of Creativity in Musical Improvisation.

Creativity has been defined as requiring both novelty and effectiveness, but little is known about how this standard definition applies in music. Here, we present results from a pilot study in which we combine behavioral testing in musical improvisation and structural neuroimaging to relate brain structure to performance in a creative musical improvisation task. Thirty-eight subjects completed a novel improvisation continuation task and underwent T1 MRI. Recorded performances were rated by expert jazz instructors for creativity. Voxel-based morphometric analyses on T1 data showed that creativity ratings were negatively associated with gray matter volume in the right inferior temporal gyrus and bilateral hippocampus. The duration of improvisation training, which was significantly correlated with creativity ratings, was negatively associated with gray matter volume in the rolandic operculum. Together, results show that musical improvisation ability and training are associated with gray matter volume in regions that are previously linked to learning and memory formation, perceptual categorization, and sensory integration. The present study takes a first step towards understanding the neuroanatomical basis of musical creativity by relating creative musical improvisation to individual differences in gray matter structure.

Midterm Results of the Ponseti Method for Treatment of Clubfoot in Patients With Spina Bifida.

BACKGROUND: Clubfoot occurs in 30% to 50% of patients with spina bifida. The Ponseti casting method has changed treatment of idiopathic clubfoot to a primarily nonoperative regimen. The Ponseti method is now widely applied to clubfoot in spina bifida, however, few studies report treatment outcomes. Most available studies include heterogeneous diagnoses or short-term results. The purpose of this study is to report midterm outcomes in patients with spina bifida and clubfoot treated with the Ponseti method. METHODS: IRB-approved retrospective chart review of 17 consecutive patients (26 feet) below 1 year of age with spina bifida and clubfoot treated with Ponseti method. Charts reviewed for age at treatment initiation, number of casts, surgeries performed, recurrence of deformity, and further treatments. Primary outcome was recurrence of deformity requiring further treatment. Data were analyzed using t tests for means and χ tests for categorical data. RESULTS: Initial correction was achieved in 26 of 26 feet patients. A total of 23 of 26 feet patients underwent a surgical procedure for the tendo-Achilles at an average age of 105 days, 12 percutaneous tenotomies (percT) and 11 open tendonectomy (openT). At average follow-up of 5 (1.8 to 7.5) years, 11 feet (42.3%) in 8 patients were successfully treated with Ponseti method. Of the 15 feet (57.7%) with recurrence, 10 required posterior releases, 4 posterior-medial-lateral releases and 1 tendon transfers. Average age at further treatment was 1.5 years (0.9 to 3.1 y). Those with recurrence required more casts before tendon surgery (7.6 vs. 6.1, P=0.02). A total of 100% patients (12/12) with percT had recurrence of deformity, compared with 18% (2/11) of patients with openT (P<0.0005). CONCLUSIONS: Midterm evaluation of Ponseti method for clubfoot in spina bifida shows a successful outcome in 42.3%. Recurrence with openT was significantly lower than percT and also substantially lower than previously published recurrence rates in spina bifida (33.3% to 68%). In spina bifida, Ponseti method leads to reliable initial correction and is useful to decrease extensive soft tissue release. An open excision of the Achilles should be performed. Families should be counseled about high risk of recurrence and potential need for further treatment. LEVEL OF EVIDENCE: Level III-retrospective comparative study.

Jazz musicians reveal role of expectancy in human creativity.

Creativity has been defined as the ability to produce work that is novel, high in quality, and appropriate to an audience. While the nature of the creative process is under debate, many believe that creativity relies on real-time combinations of known neural and cognitive processes. One useful model of creativity comes from musical improvisation, such as in jazz, in which musicians spontaneously create novel sound sequences. Here we use jazz musicians to test the hypothesis that individuals with training in musical improvisation, which entails creative generation of musical ideas, might process expectancy differently. We compare jazz improvisers, non-improvising musicians, and non-musicians in the domain-general task of divergent thinking, as well as the musical task of preference ratings for chord progressions that vary in expectation while EEGs were recorded. Behavioral results showed for the first time that jazz musicians preferred unexpected chord progressions. ERP results showed that unexpected stimuli elicited larger early and mid-latency ERP responses (ERAN and P3b), followed by smaller long-latency responses (Late Positivity Potential) in jazz musicians. The amplitudes of these ERP components were significantly correlated with behavioral measures of fluency and originality on the divergent thinking task. Together, results highlight the role of expectancy in creativity.