MR Imaging of Pediatric Neuroblastoma: Is Gadolinium Enhancement Necessary for Evaluation of Image-Defined-Risk Factors?

Background: Pre-treatment stratification and outcomes of neuroblastoma patients often depend on the assessment of image-defined risk factors (IDRFs) on MR Imaging, usually using Gadolinium-contrast materials which are cautioned in pediatrics. We aimed to address whether gadolinium contrast-enhanced sequences are necessary to identify the presence/absence of IDRFs. Methods: Patients with neuroblastoma with MR imaging were retrospectively identified from 2005 to 2021. Ninety confirmed IDRFs were evaluated in 23 patients. Corresponding MR studies were anonymized, randomized, and independently evaluated by 3 fellowship-trained pediatric radiologists. Each radiologist assessed the studies twice. At the first reading, all enhanced sequences were omitted, while in the second reading, the full study with enhanced sequences were included. Consensus reading was obtained among readers. Inter- and intra-rater agreements using Kappa statistics (κ) as well as the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of non-enhanced MR in assessing IDRFs with respect to enhanced MR were calculated. Results: There were substantial (ĸ: 0.64-0.73) intra-reader agreements, and moderate to substantial (ĸ: 0.57-0.62) inter-reader agreements among radiologists in identifying IDRFs using non-enhanced MR. Non-enhanced MR had a sensitivity of 87.8% (95% CI [79-94]), specificity of 93% (89-96), PPV of 82.3 (73-89), NPV of 95.4 (92-98), and accuracy of 91.6 (88-94) in identifying IDRFs. However, 5/23 patients (21.7%) had a change in staging with the inclusion of contrast sequences. Conclusion: Although contrast sequences have a role in IDRF assessment, the majority can be adequately assessed on MR without gadolinium-contrast enhancement. Validation in a larger cohort is an important next step.

Body Composition, Sarcopenic Obesity, and Cognitive Function in Older Adults: Findings From the National Health and Nutrition Examination Survey (NHANES) 1999-2002 and 2011-2014.

OBJECTIVE: Sarcopenic-obesity (SO) is characterized by the concomitant presence of low muscle mass and high adiposity. This study explores the association of body composition and SO phenotypes with cognitive function in older adults. METHODS: Cross-sectional data in older adults (≥60 years) from NHANES 1999-2002 and 2011-2014 were used. In the 1999-2002 cohort, phenotypes were derived from body mass index (BMI) and dual-X-ray-absorptiometry, and cognition was assessed the by Digit-Symbol-Substitution-Test (DSST). In the 2011-2014 cohort, phenotypes were derived from BMI, waist-circumference (WC), and hand-grip-strength (HGS). Cognition was assessed using four tests: DSST, Animal Fluency, the Consortium-to-Establish-a-Registry-for-Alzheimer's-Disease-Delayed-Recall, and Word Learning. Mediation analysis was conducted to evaluate the contribution of inflammation (C-reactive-protein, CRP) and insulin resistance (Homeostatic-Model-Assessment-for-Insulin-Resistance, HOMA-IR) to the association between body composition and cognitive outcomes. RESULTS: The SO phenotype had the lowest DSST mean scores (p < 0.05) and was associated with a significant risk of cognitive impairment [Odds Ratio (OR) = 1.9; 95%CI 1.0-3.7, p = 0.027] in the 1999-2002 cohort. A higher ratio of fat mass and fat free mass (FM/FFM) also showed a greater risk of cognitive impairment (OR = 2.0; 95%CI 1.3-3.1, p = 0.004). In the 2011-2014 cohort, the high WC-Low HGS group showed significantly lower scores on all four cognitive tests (p < 0.05) and a higher risk of cognitive impairment. CRP and HOMA-IR were significant partial mediators of the association between FM/FFM and DSST in the 1999-2002 cohort. CONCLUSIONS: The SO phenotype was associated with a higher risk of cognitive impairment in older adults. Insulin resistance and inflammation may represent key mechanisms linking SO to the development of cognitive impairment.

Practical uses of the BENCHMARK™ BMX®81 in the road less travelled: Guide catheter comparison for radial access in neurovascular intervention.

BACKGROUND: Radial arterial access has gained interest for neurovascular procedures in recent years. Although there are no randomized control trials for neurointervention procedures using radial access, there is growing literature demonstrating its feasibility and favorable outcomes. Equipment technical improvements, like the recently introduced BENCHMARK™ BMX®81 System, have made radial navigation safer, with improved maneuverability and support for a variety of procedures. We present a multicenter case series highlighting our institutional radial access experience comparing the BMX®81 with alternative catheters. METHODS: Multicenter retrospective cohort study of 80 patients who underwent neurovascular procedures through a radial approach. In half of the cases a BENCHMARK™ BMX®81 System was used. The comparison group consisted of the BENCHMARK™071 and 96, Neuron MAX®088 and BALLAST™ systems. Procedures included endovascular thrombectomy, carotid and brachiocephalic artery stenting, middle meningeal artery embolization, flow diverter stenting, vertebral artery sacrifice, aneurysm coiling, and WEB™ device deployment. RESULTS: In our series, the BMX®81 was successful in the navigation of the anatomy to the target location in 95% of cases. No radial access or BMX®81 related complications were identified. There was no significant difference in fluoroscopy time between the BMX81 and the comparison group. Four patients in the comparison group had catheter-related complications due to vasospasm. Eighty-six percent of BMX®81 cases had satisfactory outcomes and no technical difficulties. The remainder presented technical difficulties, but none of these were considered secondary to the puncture site or support structure. CONCLUSIONS: The BENCHMARK™ BMX®81 System is a recently developed guiding catheter which has design and size features supporting radial access for a variety of neurovascular interventions. Early multicenter experience highlights the ease of use and versatility of this new catheter as an alternative to transfemoral access as well as other catheters used for radial access.

Bed-rest and exercise remobilization: Concurrent adaptations in muscle glucose and protein metabolism.

BACKGROUND: Bed-rest (BR) of only a few days duration reduces muscle protein synthesis and induces skeletal muscle atrophy and insulin resistance, but the scale and juxtaposition of these events have not been investigated concurrently in the same individuals. Moreover, the impact of short-term exercise-supplemented remobilization (ESR) on muscle volume, protein turnover and leg glucose uptake (LGU) in humans is unknown. METHODS: Ten healthy males (24 ± 1 years, body mass index 22.7 ± 0.6 kg/m2) underwent 3 days of BR, followed immediately by 3 days of ESR consisting of 5 × 30 maximal voluntary single-leg isokinetic knee extensions at 90°/s each day. An isoenergetic diet was maintained throughout the study (30% fat, 15% protein and 55% carbohydrate). Resting LGU was calculated from arterialized-venous versus venous difference across the leg and leg blood flow during the steady-state of a 3-h hyperinsulinaemic-euglycaemic clamp (60 mU/m2/min) measured before BR, after BR and after remobilization. Glycogen content was measured in vastus lateralis muscle biopsy samples obtained before and after each clamp. Leg muscle volume (LMV) was measured using magnetic resonance imaging before BR, after BR and after remobilization. Cumulative myofibrillar protein fractional synthetic rate (FSR) and whole-body muscle protein breakdown (MPB) were measured over the course of BR and remobilization using deuterium oxide and 3-methylhistidine stable isotope tracers that were administered orally. RESULTS: Compared with before BR, there was a 45% decline in insulin-stimulated LGU (P < 0.05) after BR, which was paralleled by a reduction in insulin-stimulated leg blood flow (P < 0.01) and removal of insulin-stimulated muscle glycogen storage. These events were accompanied by a 43% reduction in myofibrillar protein FSR (P < 0.05) and a 2.5% decrease in LMV (P < 0.01) during BR, along with a 30% decline in whole-body MPB after 2 days of BR (P < 0.05). Myofibrillar protein FSR and LMV were restored by 3 days of ESR (P < 0.01 and P < 0.01, respectively) but not by ambulation alone. However, insulin-stimulated LGU and muscle glycogen storage were not restored by ESR. CONCLUSIONS: Three days of BR caused concurrent reductions in LMV, myofibrillar protein FSR, myofibrillar protein breakdown and insulin-stimulated LGU, leg blood flow and muscle glycogen storage in healthy, young volunteers. Resistance ESR restored LMV and myofibrillar protein FSR, but LGU and muscle glycogen storage remained depressed, highlighting divergences in muscle fuel and protein metabolism. Furthermore, ambulation alone did not restore LMV and myofibrillar protein FSR in the non-exercised contralateral limb, emphasizing the importance of exercise rehabilitation following even short-term BR.

Statistical analysis plan for a cluster randomised controlled trial to compare screening, feedback and intervention for child anxiety problems to usual school practice: identifying Child Anxiety Through Schools-identification to intervention (iCATS-i2i).

BACKGROUND: The Identifying Child Anxiety Through Schools-identification to intervention (iCATS-i2i) trial is being conducted to establish whether 'screening and intervention', consisting of usual school practice plus a pathway comprising screening, feedback and a brief parent-led online intervention (OSI: Online Support and Intervention for child anxiety), bring clinical and health economic benefits compared to usual school practice and assessment only - 'usual school practice', for children aged 8-9 years in the following: (1) the 'target population', who initially screen positive for anxiety problems according to a two-item parent-report child anxiety questionnaire - iCATS-2, and (2) the 'total population', comprising all children in participating classes. This article describes the detailed statistical analysis plan for the trial. METHODS AND DESIGN: iCATS-i2i is a definitive, superiority, pragmatic, school-based cluster randomised controlled trial (with internal pilot), with two parallel groups. Schools are randomised 1:1 to receive either screening and intervention or usual school practice. This article describes the following: trial objectives and outcomes; statistical analysis principles, including detailed estimand information necessary for aligning trial objectives, conduct, analyses and interpretation when there are different analysis populations and outcome measures to be considered; and planned main analyses, sensitivity and additional analyses. TRIAL REGISTRATION: ClinicalTrials.gov ISRCTN76119074. Registered on 4 January 2022.

Combining diaries and accelerometers to explain change in physical activity during a lifestyle intervention for adults with pre-diabetes: A PREVIEW sub-study.

Self-report and device-based measures of physical activity (PA) both have unique strengths and limitations; combining these measures should provide complementary and comprehensive insights to PA behaviours. Therefore, we aim to 1) identify PA clusters and clusters of change in PA based on self-reported daily activities and 2) assess differences in device-based PA between clusters in a lifestyle intervention, the PREVIEW diabetes prevention study. In total, 232 participants with overweight and prediabetes (147 women; 55.9 ± 9.5yrs; BMI ≥25 kg·m-2; impaired fasting glucose and/or impaired glucose tolerance) were clustered using a partitioning around medoids algorithm based on self-reported daily activities before a lifestyle intervention and their changes after 6 and 12 months. Device-assessed PA levels (PAL), sedentary time (SED), light PA (LPA), and moderate-to-vigorous PA (MVPA) were assessed using ActiSleep+ accelerometers and compared between clusters using (multivariate) analyses of covariance. At baseline, the self-reported "walking and housework" cluster had significantly higher PAL, MVPA and LPA, and less SED than the "inactive" cluster. LPA was higher only among the "cycling" cluster. There was no difference in the device-based measures between the "social-sports" and "inactive" clusters. Looking at the changes after 6 months, the "increased walking" cluster showed the greatest increase in PAL while the "increased cycling" cluster accumulated the highest amount of LPA. The "increased housework" and "increased supervised sports" reported least favourable changes in device-based PA. After 12 months, there was only minor change in activities between the "increased walking and cycling", "no change" and "increased supervised sports" clusters, with no significant differences in device-based measures. Combining self-report and device-based measures provides better insights into the behaviours that change during an intervention. Walking and cycling may be suitable activities to increase PA in adults with prediabetes.

Hybrid Evaluation of a Lifestyle Change Program to Prevent the Development of Type 2 Diabetes Among Individuals With Prediabetes: Intended and Observed Changes in Intervening Mechanisms.

BACKGROUND: Lifestyle interventions can prevent type 2 diabetes (T2D) by successfully inducing behavioral changes (eg, avoiding physical inactivity and sedentariness, increasing physical activity and/or healthy eating) that reduce body weight and normalize metabolic levels (eg, HbA1c). For interventions to be successful, it is important to influence "behavioral mechanisms" such as self-efficacy, which motivate behavioral changes. Theory-based expectations of how self-efficacy, chronic stress, and mood changed over time were investigated through a group-based behavior change intervention (PREMIT). At 8 intervention sites, PREMIT was offered by trained primary care providers in 18 group-sessions over a period of 36 months, divided into 4 intervention phases. Adherence to the intervention protocol was assessed. METHOD: Participants (n = 962) with overweight and prediabetes who had achieved ≥8% weight loss during a diet reduction period and completed the intervention were categorized into 3 groups: infrequent, frequent, or very frequent group sessions attendance. The interactions between participation in the group sessions and changes in self-efficacy, stress, and mood were multivariate tested. Intervention sites were regularly asked where and how they deviated from the intervention protocol. RESULTS: There was no increase in the participants' self-efficacy in any group. However, the level of self-efficacy was maintained among those who attended the group sessions frequently, while it decreased in the other groups. For all participants, chronic stress and the frequency of attending group sessions were inversely related. Significant differences in mood were found for all groups. All intervention centers reported specific activities, additional to intervention protocol, to promote participation in the group sessions. CONCLUSIONS: The results suggest that the behavioral changes sought by trained primary care providers are related to attendance frequency and follow complex trajectories. The findings also suggest that group-based interventions in naturalistic primary care settings aimed at preventing T2D require formats and strategies that encourage participants to attend group sessions regularly.