BackgroundThe increasing number of childhood cancer survivors and their well-established risk of cancer-related morbidity strongly support the need for effective health promotion (HP) programs. Existing literature suggests that HP interventions may support behaviour change and reduce the severity of some adverse effects associated with cancer and its treatments. However, uncertainty remains regarding the acceptability of these interventions to families during the cancer journey and their effectiveness in improving children's functional outcomes. This study aimed to assess the acceptability of a HP program from the perspective of families affected by cancer and to explore whether participation in the program was associated with improved functional outcomes compared to standard care.MethodsA mixed-methods study was used. Acceptability was assessed through questionnaires completed by parents (n = 30) and a semi-structured exit interviews conducted with a subgroup of adolescents (n = 6) and parents (n = 12) who participated in the program. Preliminary effectiveness on functional outcomes was evaluated using an age-appropriate performance-based assessment [Movement ABC-2 (MABC-2) or Assessment of Motor and Process Skills (AMPS)] administered to children and adolescents (n = 45) in the intervention group and compared with a control group that received standard care (n = 29).ResultsThe HP program was perceived as acceptable and positively influenced participants’ experiences during the cancer journey. Families described the program as supportive, motivating, and emotionally meaningful. However, no statistically significant differences in functional outcomes were observed between the intervention and control group.ConclusionPreliminary findings support the acceptability of implementing a HP program in a pediatric oncology clinical setting and suggest that a full-scale trial is warranted. Further research is needed to better understand how HP interventions can be optimized to improve functional outcomes among children and adolescents affected by cancer.
The gut microbiome is increasingly recognized as a key modulator of cancer immunotherapy efficacy. Given that diet is one of the most important determinants of the gut microbiome composition and function, nutritional strategies have emerged as promising tools to modulate anti-tumor immune responses. Here, we demonstrate that dietary supplementation with inulin reduces tumor growth and enhances αPD-1 efficacy in mice. These effects were associated with increased frequencies of intra-tumoral CD8⁺ and CD4⁺ T cells, particularly CCR9⁺CXCR3⁺ subsets, and enrichment of beneficial taxa such as Akkermansia and Lachnospiraceae, alongside elevated short-chain fatty acids (SCFA) levels. Among the SCFA, butyrate alone recapitulated the anti-tumor effect of inulin and had an additive effect when combined with αPD-1 therapy in a CD8⁺ T cell-dependent manner. Butyrate exerted its anti-tumor effects by transcriptional changes in CD8⁺ T cells involving activation of proliferation, trafficking, and metabolic pathways. In a cohort of 117 non-small cell lung cancer (NSCLC) patients amenable to immunotherapy, the median dietary fiber intake was lower than previously published studies but correlated with enrichment of Faecalibacterium praunitzii and metabolic pathways related to sucrose degradation and tryptophan biosynthesis. Collectively, our findings highlight the therapeutic potential of targeting diet-microbiome-immune system interactions to improve cancer immunotherapy outcomes.
BACKGROUND:Metabolic dysfunction-associated steatotic liver disease (MASLD) is increasingly prevalent among adolescents, especially those with obesity. It is the leading cause of liver-related morbidity and mortality and can progress to metabolic dysfunction-associated steatohepatitis, and eventually irreversible cirrhosis. There is currently no medical treatment recommended for MASLD in adolescents. Nutritional interventions, such as polyphenol supplementation, could be a non-pharmacological option to improve metabolic outcomes. OBJECTIVES:This pilot study aimed to preliminarily assess the impact of a 60-day polyphenol supplementation on measured resting energy expenditure (mREE) by indirect calorimetry (IC) in adolescents with MASLD. It also compared mREE by IC with predicted resting energy expenditure (pREE) using the WHO and Schofield formulae. METHODS:This single-blind randomized controlled trial enrolled 23 adolescents with MASLD, of which 11 completed IC assessments before and after the 60-day polyphenol supplementation (intervention group, n = 5) or no supplementation (controls, n = 6). There was no placebo. Caloric intake was assessed to evaluate its impact on mREE and mREE was compared to pREE using the WHO and Schofield equations. RESULTS:Participants in the intervention group had a statistically significant increase in mREE between the two visits (+89.6 kcal/day, p = 0.037), while no difference was found in the control group. When compared to the control group, the intervention group had a greater variation in mREE between visits (+100.4 kcal/day, p = 0.021). No significant changes were observed when adjusting mREE for body weight. Also, there were no significant changes in body weight in the two groups between the visits. Both the WHO and Schofield equations overestimated pREE with an average percentage of pREE of 88.8% and 91.0%, respectively. CONCLUSIONS:Although several methodological limitations prevent clear conclusions from being drawn at this stage, this study suggests that polyphenol supplementation could increase REE in adolescents with MASLD and that the WHO and Schofield equations tend to overestimate REE in obese patients.
The adoption of protective health behaviors, such as physical activity (PA) and healthy nutritional practices during childhood cancer treatments should be encouraged. This study aimed to document PA levels and diet quality before and after a multidisciplinary family lifestyle intervention, and to assess whether differences in PA levels and diet quality were associated with the degree of participation in the intervention. A multidisciplinary intervention (exercise intervention, nutritional, psychosocial support) was offered to families of children receiving treatments for childhood cancer. PA levels were assessed by self-reported total, moderate, and vigorous intensity minutes of physical activity. Diet quality was assessed using a dietary quality indicator. Participation in the intervention was measured by overall and domain-specific points of contact. We used non-parametric tests to evaluate changes over time and differences with an ad hoc comparison group. In 38 participants, we found that there was a significant difference in total minutes of PA pre- and post-intervention (p = 0.022, r = 0.27), but no difference in diet quality (p = 0.136, r = 0.19). We found that minutes of vigorous intensity PA improved rather than deteriorated (OR = 2.19, 95
Autism spectrum disorder (ASD) is a group of neurodevelopmental disorders defined by stereotyped behavior and challenges in social communication and social interaction. ASD is associated with various comorbidities, including anxiety, gastrointestinal (GI) symptoms and sleep disorders. Evidence supports an association between intestinal dysbiosis and the severity of ASD-related symptoms. Probiotic intake was suggested to restore microbial homeostasis and decrease neurobehavioral, GI and sleep symptoms in individuals diagnosed with autism. This study aims to evaluate the acceptability and safety of a Bio-K + probiotics beverage in autistic children aged 4 to 11 years and the feasibility of the proposed research protocol to measure its impact on behaviors and comorbidities. The 30-week study consisted of daily supplementation with Bio-K + probiotics for 14 weeks. Acceptability and safety were monitored throughout the study. Feasibility was assessed by comparing recruitment and completion rates to pre-established thresholds. Preliminary impact of supplementation on behaviors (Autism Treatment Evaluation Checklist (ATEC) score), GI symptoms and sleep disorders was evaluated. Of the 23 children recruited (mean age 6.7 ± 2.2 years, 70
Background: Adolescent idiopathic scoliosis (AIS) is defined as a three-dimensional spinal deformity of unknown cause that affects children between the ages of 10 and 18 years. Studies have shown that girls with AIS have different anthropometric features than their peers such as taller stature and lower body mass index. Dysfunctional energy metabolism could be involved in the discrepancies observed in AIS patients, and the gut microbiota is an important regulator of metabolic hormones. In this study, we aimed to compare gut microbiota composition, diversity and short-chain fatty acid (SCFA) between patients with AIS and healthy controls and to study their relation to metabolic hormones, anthropometry, and bone density, while taking diet and exercise into account. Methods: Nineteen age-matched pairs of AIS and control female participants were included in the study. A subset of 20 participants (9 AIS girls and 11 controls) provided fecal samples. Dietary intake and physical activity were assessed using questionnaires. Gut microbiota composition was investigated using 16S rRNA sequencing, while SCFA concentrations in feces were quantified using liquid chromatography-mass spectrometry. Results: AIS participants consumed less dietary fibers and engaged in less moderate-to-intense physical activity compared to controls. Fecal concentrations of the SCFA isobutyrate, valerate and isovalerate tended to be higher in AIS, though differences were not statistically significant. Gut microbiota α/β diversities were not statistically different between AIS participants and controls, although there were trends for differences within AIS participant α-diversity based on disease severity. Furthermore, there were several genera which trended towards being different between these populations, and our results suggest a switch in bacterial succinotypes. Additionally, correlations between fecal SCFA and adipokines or incretins were inversed in AIS participants as compared to controls. Conclusion: This pilot study suggests that gut microbiota and SCFA may be associated with AIS, but further research is needed to clarify their potential roles in disease development and progression.
Metabolic syndrome (MetS) constitutes a spectrum of interconnected conditions comprising obesity, dyslipidemia, hypertension, and insulin resistance (IR). While a singular, all-encompassing treatment for MetS remains elusive, an integrative approach involving tailored lifestyle modifications and emerging functional food therapies holds promise in preventing its multifaceted manifestations. Our main objective was to scrutinize the efficacy of cranberry proanthocyanidins (PAC, 200 mg/kg/day for 12 weeks) in mitigating MetS pathophysiology in male mice subjected to standard Chow or high-fat/high-fructose (HFHF) diets while unravelling intricate mechanisms. The administration of PAC, in conjunction with an HFHF diet, significantly averted obesity, evidenced by reductions in body weight, adiposity across various fat depots, and adipocyte hypertrophy. Similarly, PAC prevented HFHF-induced hyperglycemia and hyperinsulinemia while also lessening IR. Furthermore, PAC proved effective in alleviating key risk factors associated with cardiovascular diseases by diminishing plasma saturated fatty acids, as well as levels of triglycerides, cholesterol, and non-HDL-C levels. The rise in adiponectin and drop in circulating levels of inflammatory markers showcased PAC's protective role against inflammation. To better clarify the mechanisms behind PAC actions, gut-liver axis parameters were examined, showing significant enhancements in gut microbiota composition, microbiota-derived metabolites, and marked reductions in intestinal and hepatic inflammation, liver steatosis, and key biomarkers associated with endoplasmic reticulum (ER) stress and lipid metabolism. This study enhances our understanding of the complex mechanisms underlying the development of MetS and provides valuable insights into how PAC may alleviate cardiometabolic dysfunction in HFHF mice.
Children diagnosed with cancer are vulnerable to long-term health issues. Engaging in physical activity (PA) and adopting a healthy diet could mitigate these risks. This study aimed to understand the role of variables from the Theory of Planned Behavior (TPB) in adherence to healthy/unhealthy PA and nutrition scenarios. Through convenience sampling, four ad hoc questionnaires measuring variables from the TPB were completed by 96 parents of children diagnosed with cancer in paper format or via a secure online platform to assess attitude, perceived behavioral control (PBC), subjective norms (SN), and intention. We performed a MANOVA and multiple linear regressions. We found an effect of behavior domain (F(3, 4828.66) = 6.467, p < 0.001, ηp2 = 0.004), and scenario (F(3, 152.86) = 76.495, p < 0.001, ηp2 = 0.600). Intention was a complete intermediary variable between attitude/SN and healthy nutrition. Attitude, PBC, and intention are promising targets for PA and nutrition behaviors. SN should also be targeted for nutrition behaviors.
2567 Background: The gut microbiome is a modulator of ICI activity. Diet is among the most important factors influencing the gut microbiome. We previously showed that high fiber was not associated with outcome in NSCLC, in contrast to melanoma. However, the impact of dietary patterns and specific nutrients on ICI outcomes in NSCLC is unknown. Methods: At the CHUM Microbiome Centre, a nutritionist prospectively collected dietary history using a validated DHQ-II survey from 147 patients (pts) with advanced NSCLC treated with ICI alone or in combination with chemotherapy. Global dietary patterns and a systematic screen of 72 macro- and micronutrients (cut-offs defined by median) were examined for their association with progression-free survival (PFS) in univariable and multivariable cox-regression analyses. Associations between diet and immune-related adverse events (irAE) were examined. In 69 pts, shotgun metagenomic sequencing (WMS) was performed on fecal samples to determine differential abundance of bacteria using linear discriminant analyses, heatmaps, and MaAsLin2. Results: Median age was 68, 46% were male. Median follow-up was 13 months. Total caloric intake adjusted for basal metabolic rate (Mifflin-St Jeor equation using BMI and activity level) was not associated with PFS (p = 0.3). In univariable analyses, the following nutrients were associated with improved PFS: vitamin K (HR 0.62, p = 0.03), fat (HR 0.65, p = 0.04); while the following were associated with inferior PFS: starch (HR 1.61, p = 0.03), carbohydrates (HR 1.56, p = 0.04), sucrose (HR 1.62, p = 0.03), and iron (HR 1.7, p = 0.016). In a multivariable analysis examining all macro- and micronutrients and adjusting for BMI, vitamin K intake was significantly associated with improved PFS (HR 0.60, 95% CI 0.37, 0.97, p = 0.04). Fat-based diets such as keto-like diet (high fat, low starch) was associated with improved PFS in univariable (HR, 0.47, p = 0.008) and multivariable analyses (HR 0.37, 95%CI 0.2, 0.68, p = 0.001). Compared to high starch diet, western diet (high fat, high starch) was associated with increased risk of any grade irAE (24% vs 54%, respectively, p = 0.01). WMS analyses revealed biologically relevant signals; fat-based diets were associated with enrichment of favorable commensal bacteria such as Ruminococcus lactaris , Butyricimonas faecihominis , Lachnospiraceae spp, with low fat associated with deleterious Veillonella atypica . Starch-based diets were associated with high Prevotella spp. Sucrose-enriched diets were enriched with Candidatus saccharibacteria , a known sucrose-fermenting bacteria. Conclusions: Our results demonstrate the importance of diet on ICI outcomes in NSCLC and WMS results suggest this is mediated by the gut microbiome. Diet is a modifiable lifestyle factor which may be targeted to improve ICI activity, meriting study in a randomized trial.
Background/Objectives: Pediatric cancer survivors are at greater risk of cardiometabolic complications than their peers. This study evaluates the preliminary impact of the VIE (Valorization, Implication, Education) intervention, which integrates nutrition, physical activity, and psychological support, on dietary intake and cardiometabolic health among children and adolescents during cancer treatment. Methods: This comparative study includes pediatric cancer patients recruited to either the VIE intervention group or a control group receiving standard care. Post-treatment data on dietary intake, anthropometric measures, blood pressure, and biochemical parameters were compared between groups and stratified by level of involvement in the nutritional intervention and age at diagnosis (children and adolescents). Results: In the intervention group, 45 participants were included (51.1% male, mean age at evaluation 10.2 ± 4.5 years, mean time since end of treatment of 1.3 ± 0.8 years), and the control group comprised 77 participants (44.2% male, mean age at evaluation 12.0 ± 5.6 years, mean time since end of treatment of 1.4 ± 0.8 years). The intervention group had lower total caloric intake (mean: 1759 ± 513 vs. 1997 ± 669 kcal, p = 0.042) and higher calcium intake (mean: 567 ± 240 vs. 432 ± 197 mg/1000 kcal, p = 0.001). The participants who were highly involved in the nutritional intervention had greater protein-derived energy intake than the controls (mean: 17 ± 5 vs. 15 ± 4%, p = 0.029). While there was a tendency for a lesser proportion of cardiometabolic risk factors in the adolescents from the intervention group, the differences did not reach statistical significance. Conclusions: The VIE intervention improved some specific dietary intakes in the medium term after treatment completion but did not significantly impact cardiometabolic health outcomes. Additional strategies are needed to improve the diet of pediatric cancer patients, and further research is warranted to assess the long-term impact of such interventions.
Acute lymphoblastic leukemia (ALL) is the most common pediatric cancer. Contributory factors such as inflammation and oxidative stress, in response to drug therapies, may induce premature aging and cellular senescence with a severe impact on cardiometabolic health. Premature immunoaging through cellular senescence can lead to lower thymic output of T-cell lymphocytes translated into lower circulating T-cell receptor excision circles (TRECs). We hypothesized TRECs levels are associated with diet quality and impacted by oxidative and inflammatory status in survivors of childhood ALL (cALL). Adolescents and young adults cALL survivors from the PETALE cohort (n = 241, 22.1 ± 6.3 years at diagnosis, 49.4% males) were assessed for TREC levels and adherence to six diet quality indexes. Healthy Diet Indicator (HDI) was associated with TREC levels (β = 50.0, p = 0.005, adjusted p = 0.03). Interleukin-6 (IL-6) and C-reactive protein (CRP) were found negatively associated with TREC levels (β = -80 and -80.1, p = 0.017 and 0.026, respectively) HDI. Further analysis revealed IL-6 and CRP to be moderating factors, but not mediators, of the association between HDI and TRECs. This study supports a positive impact of a healthy diet on premature aging of the immune system in survivors of cALL and unveils the moderating role of inflammation in this association.
One way to prevent or minimize adverse effects from pediatric cancer is to adopt and maintain healthy behaviours. However, there is limited knowledge on how to successfully implement health promotion (HP) interventions in clinical settings. This study aimed to determine the factors affecting the participation in and implementation of an HP program from the perspective of adolescents impacted by cancer, parents of children or adolescents impacted by cancer, and healthcare professionals (HCPs). We conducted semi-structured interviews with adolescents and parents, and focus groups with HCPs. Data were analysed using thematic analysis. A total of five adolescents, nine parents, and eleven HCPs were interviewed. Three major themes were determined: (1) facilitators to participation and implementation, (2) barriers to participation and implementation, and (3) suggestions for improvement. Factors identified as keys to participation include tailoring interventions to families’ specific needs and social support. Organizational barriers, health issues, and a lack of interest or need hampered participation in the program. Implementation was positively impacted by the interventions’ perceived relevance and negatively by their lack of integration in clinical care. While HP interventions hold promise for improving quality of life, successful implementation requires addressing the multifaceted challenges faced by participants and providers.
Phenomenology in anorexia nervosa (AN) appears to be subject to epigenetic regulation via DNA methylation. The micronutrients B12 and betaine contribute directly to DNA methylation and have been shown to be abnormally elevated in blood samples from people with AN. We measured plasma B12 and betaine levels, as well as leukocyte DNA methylation levels, among women with active AN (AN-active group), those in 1-year remission from AN (AN-remitted group), and those who had never experienced an eating disorder (NED group). We compared the groups on micronutrient levels and on the strength of association between micronutrients and methylation. We included 64 women in the AN-active group, 49 in the AN-remitted group, and 49 in the NED group. Relative to those with NED (B12: mean 339.6 [standard deviation (SD) 224.3] μmol/L; betaine: mean 33.74 [SD 17.10] μmol/L), participants with active AN showed high B12 and betaine (B12: mean 571.0 [SD 505.2] μmol/L; betaine: mean 43.73 [SD 22.50] μmol/L); AN-remitted participants had elevated B12 alone (B12: mean 588.2 [SD 379.9] μmol/L; betaine: mean 33.50 [SD 19.20] μmol/L). There were also group-based differences in the strength of association between B12 and site-specific DNA methylation at genes regulating insulin function, glucose metabolism, cell regulation, and neurotransmitter function. These associations between B12 and methylation levels were generally stronger among those without an ED than among those with either active or remitted AN. The extent to which plasma nutrient levels provide a meaningful proxy to cellular processes affecting DNA methylation is uncertain and the sample size limits the stability of results. We included only biological females in this investigation. Elevated B12 levels in AN resemble elevations reported among people with autoimmune, neoplastic, or other disorders. Such elevations imply that plasma B12 levels may misrepresent nutritional status among people with AN. Observed associations between levels of B12 and methylation at certain gene regions have ambiguous importance, but may indicate an influence of nutritional status on epigenetic mechanisms or may be the coincidence of separate processes that independently affect levels of micronutrients and DNA methylation.
Studies have revealed anthropometric discrepancies in girls with adolescent idiopathic scoliosis (AIS) compared to non-scoliotic subjects, such as a higher stature, lower weight, and lower body mass index. While the causes are still unknown, it was proposed that metabolic hormones could play a role in AIS pathophysiology. Our objectives were to evaluate the association of GLP1R A316T polymorphism in AIS susceptibility and to study its relationship with disease severity and progression. We performed a retrospective case–control association study with controls and AIS patients from an Italian and French Canadian cohort. The GLP1R rs10305492 polymorphism was genotyped in 1025 subjects (313 non-scoliotic controls and 712 AIS patients) using a validated TaqMan allelic discrimination assay. Associations were evaluated by odds ratio and 95% confidence intervals. In the AIS group, there was a higher frequency of the variant genotype A/G (4.2% vs. 1.3%, OR = 3.40, p = 0.016) and allele A (2.1% vs. 0.6%, OR = 3.35, p = 0.017) than controls. When the AIS group was stratified for severity (≤40° vs. >40°), progression of the disease (progressor vs. non-progressor), curve type, or body mass index, there was no statistically significant difference in the distribution of the polymorphism. Our results support that the GLP1R A316T polymorphism is associated with a higher risk of developing AIS, but without being associated with disease severity and progression.
Over the past three decades, significant efforts have been focused on unraveling congenital intestinal disorders that disrupt the absorption of dietary lipids and fat-soluble vitamins. The primary goal has been to gain deeper insights into intra-enterocyte sites, molecular steps, and crucial proteins/regulatory pathways involved, while simultaneously identifying novel therapeutic targets and diagnostic tools. This research not only delves into specific and rare malabsorptive conditions, such as chylomicron retention disease (CRD), but also contributes to our understanding of normal physiology through the utilization of cutting-edge cellular and animal models alongside advanced research methodologies. This review elucidates how modern techniques have facilitated the decoding of CRD gene defects, the identification of dysfunctional cellular processes, disease regulatory mechanisms, and the essential role of coat protein complex II-coated vesicles and cargo receptors in chylomicron trafficking and endoplasmic reticulum (ER) exit sites. Moreover, experimental approaches have shed light on the multifaceted functions of SAR1B GTPase, wherein loss-of-function mutations not only predispose individuals to CRD but also exacerbate oxidative stress, inflammation, and ER stress, potentially contributing to clinical complications associated with CRD. In addition to dissecting the primary disease pathology, genetically modified animal models have emerged as invaluable assets in exploring various ancillary aspects, including responses to environmental challenges such as dietary alterations, gender-specific disparities in disease onset and progression, and embryonic lethality or developmental abnormalities. In summary, this comprehensive review provides an in-depth and contemporary analysis of CRD, offering a meticulous examination of the CRD current landscape by synthesizing the latest research findings and advancements in the field.
There is currently a growing interest in the use of nutraceuticals as a means of preventing the development of complex diseases. Given the considerable health potential of milk-derived peptides, the aim of this study was to investigate the protective effects of glycomacropeptide (GMP) on metabolic syndrome. Particular emphasis was placed on the potential mechanisms mitigating cardiometabolic disorders in high-fat, high-fructose diet-fed mice in the presence of GMP or Bipro, an isocaloric control. The administration of GMP for 12 weeks reduced obesity, hyperglycemia and hyperinsulinemia caused by a high-fat, high-fructose diet, resulting in a decline in insulin resistance. GMP also lessened systemic inflammation, as indicated by decreased circulating inflammatory cytokines. In the intestinal and hepatic tissues, GMP improved homeostasis by increasing insulin sensitivity and attenuating high-fat, high-fructose-induced inflammation, oxidative stress and endoplasmic reticulum stress. Biochemical and histological analyses revealed improved hepatic steatosis and fatty acid composition in the livers of high-fat, high-fructose diet-fed mice treated with GMP compared to Bipro. A trend toward a decrease in bile acids without any marked changes in intestinal microbiota composition characterized GMP-treated animals compared to those administered Bipro. GMP offers considerable potential for fighting metabolic syndrome-related components and complications given its beneficial effects on risk factors such as inflammation, oxidative stress and endoplasmic reticulum stress without involving the intestinal microbiota.
Childhood acute lymphoblastic leukemia (cALL) survivors suffer early-onset chronic diseases classically associated with aging. Normal aging is accompanied by organ dysfunctions, including immunological ones. We hypothesize that thymic immunosenescence occurs in cALL survivors and that its severity may correlate with early-onset chronic diseases. The PETALE study is a cALL survivor cohort with an extensive cardiovascular and metabolic evaluation. The thymic immunosenescence biomarker, signal joint T-cell receptor excision circles (TREC), was evaluated and was highly correlated with age in healthy participants (n = 281) and cALL survivors (n = 248). We observed a systematic thymic immunoage accentuation in each cALL survivor compared to controls ranging from 5.9 to 88.3 years. The immunoage gain was independent of age at diagnosis and treatment modalities and was more severe for females. Thymic aging was associated with several pathophysiological parameters, was greater in survivors suffering from metabolic syndrome, but there was no significant association with global physical condition. The decrease in TREC was independent from blood cell counts, which were normal, suggesting a segmental aging of the thymic compartment. Indeed, increased plasmatic T cell regulatory cytokines IL-6, IL-7 and GM-CSF accompanied high immunoage gain. Our data reveal that cALL or its treatment trigger a rapid immunoage gain followed by further gradual thymic immunosenescence, similar to normal aging. This leads to an enduring shift in accentuated immunoage compared to chronological age. Thus, accentuated thymic immunosenescence is a hallmark of cALL survivorship and TREC levels could be useful immunosenescence biomarkers to help monitoring the health of cancer survivors.
Approximately two-thirds of survivors of childhood acute lymphoblastic leukemia (ALL) cancer develop late adverse effects post-treatment. Prior studies explored prediction models for personalized follow-up, but none integrated the usage of neural networks to date. In this work, we propose the Error Passing Network (EPN), a graph-based method that leverages relationships between samples to propagate residuals and adjust predictions of any machine learning model. We tested our approach to estimate patients' VO2 peak, a reliable indicator of their cardiac health. We used the EPN in conjunction with several baseline models and observed up to 12.16% improvement in the mean average percentage error compared to the last established equation predicting VO2 peak in childhood ALL survivors. Along with this performance improvement, our final model is more efficient considering that it relies only on clinical variables that can be self-reported by patients, therefore removing the previous need of executing a resource-consuming physical test.
Abstract Background This study constitutes a secondary analysis of a prospective cohort aiming to evaluate the potential correlation between nutritional risk and status at admission with the occurrence of post-discharge complications and hospital readmissions in children receiving care at high resource Centres. Methods Data was collected from 5 Canadian tertiary pediatric Centers between 2012 and 2016. Nutritional risk and status were evaluated at hospital admission with validated tools (STRONGkids and Subjective Global Nutrition Assessment [SGNA]) and anthropometric measurements. Thirty days after discharge, occurrence of post-discharge complications and hospital readmission were documented. Results A total of 360 participants were included in the study (median age, 6.1 years; median length of stay, 5 days). Following discharge, 24.1% experienced complications and 19.5% were readmitted to the hospital. The odds of experiencing complications were nearly tripled for participants with a high nutritional risk compared to a low risk (OR = 2.85; 95% CI [1.08–7.54]; P = 0.035) and those whose caregivers reported having a poor compared to a good appetite (OR = 2.96; 95% CI [1.59–5.50]; P < 0.001). According to SGNA, patients identified as malnourished had significantly higher odds of complications (OR, 1.92; 95% CI, 1.15–3.20; P = 0.013) and hospital readmission (OR, 1.95; 95% CI, 1.12–3.39; P = 0.017) than to those well-nourished. Conclusions This study showed that complications and readmission post-discharge are common, and these are more likely to occur in malnourished children compared to their well-nourished counterparts. Enhancing nutritional care during admission, at discharge and in the community may be an area for future outcome optimization.
Immune checkpoint inhibitors (ICI) dramatically improved outcomes of patients with non-small cell lung cancer (NSCLC). The gut microbiome has emerged as a biomarker of response to ICI in NSCLC and a potential therapeutic target. High fiber and Mediterranean diets were associated with prolonged response in patients with melanoma treated with ICI. The objective of this study was to assess the effect of diet on outcome and microbiome composition. Prospective collection of clinical and dietary data were assessed in 102 patients with NSCLC amenable to ICI. We employed a standardize food frequency questionnaire (FFQ) specific to the NSCLC population designed by a clinical nutritionist. FFQ answers were recorded electronically and analyzed using a calculation tool to estimate the median daily fiber (g/day), and surrogate markers of the Mediterranean diet; Monounsaturated fatty acids (MUFA) and Polyunsaturated fatty acids (PUFA) intake (g/1000kcal). Then correlated with progression-free survival (PFS) and overall survival (OS). Microbiome was profiled in a sub-group of 76 patients using shot-gun metagenomic, MetaPhlan4 pipeline was used to detect species, diversity index and LefSe were calculated. Among the 102 patients with NSCLC the median fiber intake was 16 g/day and did not correlate with outcome. However, Spearman correlation showed a significant association between increased PUFA or MUFA intake and longer OS (p<0,001 and p<0,001). Moreover, MUFA dietary intake correlated with a prolonged PFS (median PFS high MUFA intake: 20.0 months versus low MUFA intake: 9.1 months, p=0.02). Additionally, MUFA and PUFA intake correlated with the increase abundance of Eubacterium, Alistipes and Bifidobacterium. In this cohort, patients had a very low fiber diet, however a high MUFA and PUFA intake was associated with beneficial response and an overrepresentation of known beneficial immunogenic bacteria. These results raise the possibility that evidence-based dietary recommendations counseling using educational tools may represent an important strategy to employ the gut microbiome as a potential therapeutic target in improving the response to ICI.