Does sleep‑disordered breathing add to impairments in academic performance and brain structure usually observed in children with overweight/obesity?

Funding for open access charge: Universidad de Granada/CBUA. This work is part of a PhD thesis conducted in the Official Doctoral Programme in Biomedicine of the University of Granada, Spain. Preliminary data from this manuscript has been presented previously in The International Society of Behavioral Nutrition and Physical Activity (ISBNPA) Xchange 2021 Annual Meeting. The ActiveBrains project was funded by the Spanish Ministry of Economy and Competitiveness and the "Fondo Europeo de Desarrollo Regional (FEDER)" (DEP201347540, DEP2016-79512-R, DEP2017-91544-EXP and RYC-201109011). L.V.T.-L. is supported by a Grant from the Spanish Ministry of Science, Innovation and Universities (FPU17/04802). J.H.M. is supported by a Grant from the Spanish Ministry of Education, Culture and Sport (FPU15/02645). C.C.-S. is supported by the Spanish Ministry of Science and Innovation (FJC2018-037925-I). IEC is supported by the Spanish Ministry of Science and Innovation (RYC2019-027287-I). Additional support was obtained from the University of Granada, Plan Propio de Investigacion 2016, Excellence actions: Units of Excellence, Scientific Excellence Unit on Exercise and Health (UCEES), by the Junta de Andalucia, Consejeria de Conocimiento, Investigacion y Universidades, and European Regional Development Funds (ref. SOMM17/6107/UGR). In addition, funding was provided by the SAMID III network, RETICS, funded by the PNI + D + I 2017-2021 (Spain), ISCIII-Sub-Directorate General for Research Assessment and Promotion, the European Regional Development Fund (ERDF) (Ref. RD16/0022), the EXERNET Research Network on Exercise and Health (DEP2005-00046/ACTI; 09/UPB/19; 45/UPB/20; 27/UPB/21), the European Union's 2020 research and innovation program under grant agreement No.667302, and the HL-PIVOT network-Healthy Living for Pandemic Event Protection. Additional funding was obtained from the Andalusian Operational Programme supported with European Regional Development Funds (ERDF in English, FEDER in Spanish, project ref: B-CTS-355-UGR18).Approximately 4–11% of children suffer from sleep-disordered breathing (SDB), and children with obesity are at increased risk. Both obesity and SDB have been separately associated with poorer brain health, yet whether SDB severity affects brain health in children with obesity remains unanswered. This study aimed to examine associations of SDB severity with academic performance and brain structure (i.e., total brain and gray and white matter volumes and gray matter volume in the hippocampus) in children with overweight/obesity. One hundred nine children aged 8–12 years with overweight/obesity were included. SDB severity and its subscales (i.e., snoring, daytime sleepiness, and inattention/hyperactivity) were evaluated via the Pediatric Sleep Questionnaire (PSQ), and academic performance was evaluated with the Woodcock-Muñoz standardized test and school grades. Brain structure was assessed by magnetic resonance imaging. SDB severity was not associated with academic performance measured by the standardized test (all |β|> 0.160, P > 0.076), yet it was associated with the school grade point average (β = -0.226, P = 0.007) and natural and social science grades (β = -0.269, P = 0.024). Intention/hyperactivity seemed to drive these associations. No associations were found between SDB severity and the remaining school grades (all β 0.065) or brain volumes (all P > 0.05). Conclusion: Our study shows that SDB severity was associated with lower school grades, yet it was not associated with the standardized measurement of academic performance or with brain volumes in children with overweight/obesity. SDB severity may add to academic problems in children beyond the effects contributed by overweight/obesity status alone.Universidad de Granada/CBUASpanish Government European CommissionSpanish Government DEP201347540 DEP2016-79512-R DEP2017-91544-EXP RYC-201109011Spanish Government FPU17/04802 FPU15/02645 FJC2018-037925-I RYC2019-027287-IUniversity of Granada, Plan Propio de Investigacion 2016, Excellence actions: Units of Excellence, Scientific Excellence Unit on Exercise and Health (UCEES)Junta de Andalucia European Commission SOMM17/6107/UGRSAMID III network, RETICS - PNI + D + I 2017-2021 (Spain)ISCIII-Sub-Directorate General for Research Assessment and PromotionEuropean Commission RD16/0022EXERNET Research Network on Exercise and Health DEP2005-00046/ACTI 09/UPB/19 45/UPB/20 27/UPB/21European Commission 667302HL-PIVOT network-Healthy Living for Pandemic Event ProtectionAndalusian Operational ProgrammeEuropean Regional Development Funds (ERDF in English, FEDER in Spanish) B-CTS-355-UGR1

Comparability of published cut-points for the assessment of physical activity: Implications for data harmonization

This study aimed to compare estimations of sedentary time (SED) and time spent in physical activity (PA) intensities in children with overweight/obesity across different age-appropriate cut-points based on different body-worn attachment sites and acceleration metrics. A total of 104 overweight/obese children (10.1 ± 1.1 years old, 43 girls) concurrently wore ActiGraph GT3X+ accelerometers on their right hip and non-dominant wrist for 7 days (24 hours). Euclidean norm -1 g (ENMO) and activity counts from both vertical axis (VACounts) and vector magnitude (VMCounts) were derived. We calculated estimates of SED and light, moderate, vigorous, and moderate-to-vigorous (MVPA) intensity PA using different published cut-points for children. The prevalence of children meeting the recommended 60 min/d of MVPA was calculated. The time spent in SED and the different PA intensities largely differed across cut-points based on different attachment sites and acceleration metrics (ie, SED = 11-252 min/d; light PA = 10-217 min/d; moderate PA = 1-48 min/d; vigorous PA = 1-35 min/d; MVPA = 4-66 min/d). Consequently, the prevalence of children meeting the recommended 60 min/d of MVPA varied from 8% to 96% of the study sample. The present study provides a comprehensive comparison between available cut-points for different attachment and acceleration metrics in children. Furthermore, our data clearly show that it is not possible (and probably will never be) to know the prevalence of meeting the PA guidelines based on accelerometer data since apparent differences range from almost zero to nearly everyone meeting the guidelines

Effects of an Exercise Program on Brain Health Outcomes for Children With Overweight or Obesity. The ActiveBrains Randomized Clinical Trial

IMPORTANCE Pediatric overweight and obesity are highly prevalent across the world, with implications for poorer cognitive and brain health. Exercise might potentially attenuate these adverse consequences. OBJECTIVES To investigate the effects of an exercise program on brain health indicators, including intelligence, executive function, academic performance, and brain outcomes, among children with overweight or obesity and to explore potential mediators and moderators of the main effects of exercise. DESIGN, SETTING, AND PARTICIPANTS All preexercise and postexercise data for this 20-week randomized clinical trial of 109 children aged 8 to 11 years with overweight or obesity were collected from November 21, 2014, to June 30, 2016, with neuroimaging data processing and analyses conducted between June 1, 2017, and December 20, 2021. All 109 children were included in the intention-to-treat analyses; 90 children (82.6%) completed the postexercise evaluation and attended 70%or more of the recommended exercise sessions and were included in per-protocol analyses. INTERVENTIONS All participants received lifestyle recommendations. The control group continued their usual routines, whereas the exercise group attended a minimum of 3 supervised 90-minute sessions per week in an out-of-school setting. MAIN OUTCOMES AND MEASURES Intelligence, executive function (cognitive flexibility, inhibition, andworking memory), and academic performancewere assessed with standardized tests, and hippocampal volume was measured with magnetic resonance imaging. RESULTS The 109 participants included 45 girls (41.3%); participants had a mean (SD) body mass index of 26.8 (3.6) and a mean (SD) age of 10.0 (1.1) years at baseline. In per-protocol analyses, the exercise intervention improved crystallized intelligence, with the exercise group improving from before exercise to after exercise (mean z score, 0.62 [95%CI, 0.44-0.80]) compared with the control group (mean z score, –0.10 [95%CI, –0.28 to 0.09]; difference between groups, 0.72 SDs [95%CI, 0.46-0.97]; P < .001). Total intelligence also improved significantly more in the exercise group (mean z score, 0.69 [95%CI, 0.48-0.89]) than in the control group (mean z score, 0.07 [95% CI, –0.14 to 0.28]; difference between groups, 0.62 SDs [95%CI, 0.31-0.91]; P < .001). Exercise also positively affected a composite score of cognitive flexibility (mean z score: exercise group, 0.25 [95% CI, 0.05-0.44]; control group, –0.17 [95%CI, –0.39 to 0.04]; difference between groups, 0.42 SDs [95%CI, 0.13-0.71]; P = .005). These main effects were consistent in intention-to-treat analyses and after multiple-testing correction. There was a positive, small-magnitude effect of exercise on total academic performance (mean z score: exercise group, 0.31 [95%CI, 0.18-0.44]; control group, 0.10 [95%CI, –0.04 to 0.24]; difference between groups, 0.21 SDs [95%CI, 0.01-0.40]; P = .03), which was partially mediated by cognitive flexibility. Inhibition, working memory, hippocampal volume, and other brain magnetic resonance imaging outcomes studied were not affected by the exercise program. The intervention increased cardiorespiratory fitness performance as indicated by longer treadmill time to exhaustion (mean z score: exercise group, 0.54 [95%CI, 0.27-0.82]; control group, 0.13 [95%CI, –0.16 to 0.41]; difference between groups, 0.42 SDs [95%CI, 0.01-0.82]; P = .04), and these changes in fitness mediated some of the effects (small percentage of mediation [approximately 10%-20%]). The effects of exercise were overall consistent across the moderators tested, except for larger improvements in intelligence among boys compared with girls. CONCLUSIONS AND RELEVANCE In this randomized clinical trial, exercise positively affected intelligence and cognitive flexibility during development among children with overweight or obesity. However, the structural and functional brain changes responsible for these improvementswere not identified.Spanish Government DEP2013-47540 DEP2016-79512-R DEP2017-91544-EXPEuropean Commission European Commission European Commission Joint Research Centre 667302Alicia Koplowitz FoundationERDF (FEDER in Spanish) B-CTS-355-UGR18University of Granada, Plan Propio de Investigacion, Visiting Scholar grantsJunta de AndaluciaUnit of Excellence on Exercise, Nutrition and Health (UCEENS)European Commission SOMM17/6107/UGREXERNET Research Network on Exercise and Health DEP2005-00046/ACTIHigh Council of Sports 09/UPB/19Spanish Government FPU 14/06837 FPI-BES-2014-068829 FJC2018-037925-I FJCI-2014-19563 IJCI-2017-33642 RYC2019-027287-I FPU15/02645 FJCI-2017-33396 IJC2019-041916-IJunta de AndaluciaNational Agency for Research and Development (ANID)/BECAS Chile 72180543Ramon Areces Foundatio

Prognostic heterogeneity of adult B-cell precursor acute lymphoblastic leukaemia patients with t(1;19)(q23;p13)/TCF3-PBX1 treated with measurable residual disease-oriented protocols

Programa para el Tratamiento de Hemopatias Malignas (PETHEMA) Group (Spanish Society of Hematology, SEHH).The prognosis of t(1;19)(q23;p13)/transcription factor 3-pre-B-cell leukaemia homeobox 1 (TCF3-PBX1) in adolescent and adult patients with acute lymphoblastic leukaemia (ALL) treated with measurable residual disease (MRD)-oriented trials remains controversial. In the present study, we analysed the outcome of adolescent and adult patients with t(1;19)(q23;p13) enrolled in paediatric-inspired trials. The patients with TCF3-PBX1 showed similar MRD clearance and did not have different survival compared with other B-cell precursor ALL patients. However, patients with TCF3-PBX1 had a significantly higher cumulative incidence of relapse, especially among patients aged ≥35 years carrying additional cytogenetic alterations. These patients might benefit from additional/intensified therapy (e.g. immunotherapy in first complete remission with or without subsequent haematopoietic stem cell transplantation).This work was supported in part by CERCA/Generalitat de Catalunya SGR 2017 288 (GRC), a restricted grant from ‘La Caixa’ and Healthcare Alliance for Resourceful Medicine Offensive against Neoplasms (HARMONY)

Prognostic heterogeneity of adult B‐cell precursor acute lymphoblastic leukaemia patients with t(1;19)(q23;p13)/ TCF3‐PBX1 treated with measurable residual disease‐oriented protocols

The prognosis of t(1;19)(q23;p13)/transcription factor 3-pre-B-cell leukaemia homeobox 1 (TCF3-PBX1) in adolescent and adult patients with acute lymphoblastic leukaemia (ALL) treated with measurable residual disease (MRD)-oriented trials remains controversial. In the present study, we analysed the outcome of adolescent and adult patients with t(1;19)(q23;p13) enrolled in paediatric-inspired trials. The patients with TCF3-PBX1 showed similar MRD clearance and did not have different survival compared with other B-cell precursor ALL patients. However, patients with TCF3-PBX1 had a significantly higher cumulative incidence of relapse, especially among patients aged ≥35 years carrying additional cytogenetic alterations. These patients might benefit from additional/intensified therapy (e.g. immunotherapy in first complete remission with or without subsequent haematopoietic stem cell transplantation)

A pediatric regimen for adolescents and young adults with Philadelphia chromosome-negative acute lymphoblastic leukemia : Results of the ALLRE08 PETHEMA trial

Altres ajuts: Supported in part by grants from Fundació La Caixa and CIBERONC (JMHR and AO).Pediatric-based or -inspired trials have improved the prognosis of adolescents and young adults (AYA) with Philadelphia chromosome-negative (Ph-neg) acute lymphoblastic leukemia (ALL). This study reports the results of treatment of the ALLRE08 trial, a full pediatric trial for AYA aged 15-30 years with standard-risk (SR) ALL. From 2008 to 2018, 89 patients (38 adolescents [15-18 years] and 51 young adults [YA, 19-30 years], median age: 20 [15-29] years) were enrolled in the ALLRE08 trial. The complete response (CR) was 95%. Twenty-two patients were transferred to a high-risk (HR) protocol because of poor marrow response on day 14 (n = 20) or high-level of end-induction minimal residual response (MRD ≥ 0.25%, n = 2). Cumulative incidence of relapse (CIR) at 5 years was 35% (95%CI: 23%-47%), with significant differences between adolescents and YA: 13% (4%-28%) vs 52% (34%-67%), P = .012. No treatment-related mortality was observed in 66/66 patients following the ALLRE08 trial vs 3/23 patients moved to a HR trial. The estimated 5-year overall survival (OS) was 74% (95%CI: 63%-85%), with significantly higher rates for adolescents vs YA: 87% (95%CI: 74%-100%) vs 63% (46%-80%), P = .021. Although CIR or OS were lower in patients who were transferred to a HR trial, the differences were not statistically significant (CIR: 34% [21%-47%] vs 37% [14%-61%]; OS: 78% [66%-90%] vs 61% [31%;91%]). A full pediatric trial is feasible and effective for AYA with Ph-neg, SR-ALL, with better results for adolescents than for YA. Outcome of patients with poor early response rescued with a HR trial was not significantly inferior. A full pediatric trial is feasible and effective for adolescent and young adults with acute lymphoblastic leukemia, with better results for adolescents than for young adults. The outcome of patients showing poor early response was not significantly inferior than that observed for good responders after being transferred to a high-risk trial

Allogeneic stem cell transplantation as a curative option in relapse/refractory diffuse large B cell lymphoma: Spanish multicenter GETH/GELTAMO study

Grupo Español de Trasplante Hematopoyético (GETH) and Grupo Español de Linfoma y Trasplante Autólogo (GELTAMO).We performed a retrospective multicenter study including 140 patients with relapsed/refractory (R/R) diffuse large B cell lymphoma (DLBCL) who underwent allogeneic hematopoietic stem cell transplantation (allo-SCT) from March 1995 to November 2018. Our objective was to analyze long term outcomes. Seventy-four percent had received a previous auto-SCT (ASCT) and the median number of lines pre-allo-SCT was 3 (range 1–9). Three year-event free survival (EFS) and overall survival (OS) were 38% and 44%, respectively. Non-relapse mortality (NRM) at day 100 was 19%. Cumulative incidence of grade III–IV acute graft versus host disease (GVHD) at day 100 was 16% and moderate/severe chronic GVHD at 3 years 34%. Active disease at allo-SCT (HR 1.95, p = 0.039) (HR 2.19, p = 0.019), HCT-CI ≥ 2 (2.45, p = 0.002) (HR 2.33, p = 0.006) and donor age >37 years (HR 2.75, p = 0.014) (HR 1.98, p = 0.043) were the only independent variables both for PFS and OS, respectively. NRM was significantly modified by HCT-CI ≥ 2 (HR 4.8, p = 0.008), previous ASCT (HR 4.4, p = 0.048) and grade III–IV acute GVHD on day 100 (HR 6.13, p = 0.016). Our data confirmed that allo-SCT is a curative option for patients with R/R DLBCL, displaying adequate results for fit patients with chemosensitive disease receiving an allo-SCT from a young donor