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.

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.

Introduction Non-alcoholic fatty liver disease (NAFLD) is increasingly prevalent in obese adolescents. Increased systemic inflammation and decreased gut microbial diversity linked to obesity affect the liver and are also associated with cardiovascular diseases in adulthood. However, NAFLD and vascular alterations are reversible.Methods and analysis This pilot study evaluated the feasibility of a prospective open-label randomised controlled trial evaluating the effects of polyphenols on NAFLD and vascular parameters in obese adolescents. Children aged 12–18 years with hepatic steatosis (n=60) will be recruited. The participants will be randomised with a 1:1 allocation ratio to receive polyphenol supplementation one time per day for 8 weeks along with the clinician-prescribed treatment (group B, n=30) or to continue the prescribed treatment without taking any polyphenols (group A, n=30). The outcome measures will be collected from both the groups at day 1 before starting polyphenol supplementation, at day 60 after 8 weeks of supplementation and at day 120, that is, 60 days after supplementation. The changes in hepatic steatosis and vascular parameters will be measured using liver and vascular imaging. Furthermore, anthropometric measures, blood tests and stool samples for gut microbiome analysis will be collected. After evaluating the study’s feasibility, we hypothesise that, as a secondary outcome, compared with group A, the adolescents in group B will have improved NAFLD, vascular parameters, systemic inflammation and gut microbiome.Ethics and dissemination This study is approved by Health Canada and the hospital ethics. Participants and their parents/tutors will both provide consent. Trial results will be communicated to the collaborating gastroenterologists who follow the enrolled participants. Abstracts and scientific articles will be submitted to high-impact radiological societies and journals. ClinicalTrials.gov ID: NCT03994029. Health Canada authorisation referral number: 250 811. Protocole version 13, 2 June 2023.Trial registration number NCT03994029.

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.

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.

Supplementary Table 1 from Hepatocyte Nuclear Factor-4α Promotes Gut Neoplasia in Mice and Protects against the Production of Reactive Oxygen Species

Aim: To assess whether small-for-gestational-age (SGA) -an indicator of poor fetal growth, may affect metabolic health biomarkers in infancy and explore the predictors. Methods: This was a nested matched (1:2) prospective observational study of 65 SGA (birth weight < 10th percentile) and 130 optimal-for-gestational-age (OGA, birth weight 25th-75th percentiles, control) infants in the 3D birth cohort with subjects recruited in Canada from 1 May 2010 to 31 August 2012. The outcomes included homeostasis model assessment of insulin resistance (HOMA-IR) and beta-cell function (HOMA-eta), circulating leptin and adiponectin concentrations at age 2 years. Results: HOMA-IR, HOMA-beta, leptin and adiponectin concentrations were similar in SGA versus OGA infants. Female sex and accelerated growth in length during mid-infancy (3-12 months) were associated with higher HOMA-IR. Caucasian ethnicity and decelerated growth in weight during late infancy (12-24 months) were associated with lower HOMA-IR. Current BMI was positively associated with circulating adiponectin in SGA infants only (+13.4% [4.0%-23.7%] per BMI z score increment). Conclusion: Insulin resistance and secretion, circulating leptin and adiponectin levels were normal in SGA subjects in infancy at age 2 years. The novel observation in SGA-specific positive association between current BMI and circulating adiponectin suggests dysfunctional adiposity-adiponectin negative feedback loop development during infancy in SGA subjects.

Objective Faecal microbiota transplantation (FMT) in germ-free (GF) mice is a common approach to study the causal role of the gut microbiota in metabolic diseases. Lack of consideration of housing conditions post-FMT may contribute to study heterogeneity. We compared the impact of two housing strategies on the metabolic outcomes of GF mice colonised by gut microbiota from mice treated with a known gut modulator (cranberry proanthocyanidins (PAC)) or vehicle. Design High-fat high-sucrose diet-fed GF mice underwent FMT-PAC colonisation in sterile individual positive flow ventilated cages under rigorous housing conditions and then maintained for 8 weeks either in the gnotobiotic-axenic sector or in the specific pathogen free (SPF) sector of the same animal facility. Results Unexpectedly, 8 weeks after colonisation, we observed opposing liver phenotypes dependent on the housing environment of mice. Mice housed in the GF sector receiving the PAC gut microbiota showed a significant decrease in liver weight and hepatic triglyceride accumulation compared with control group. Conversely, exacerbated liver steatosis was observed in the FMT-PAC mice housed in the SPF sector. These phenotypic differences were associated with housing-specific profiles of colonising bacterial in the gut and of faecal metabolites. Conclusion These results suggest that the housing environment in which gnotobiotic mice are maintained post-FMT strongly influences gut microbiota composition and function and can lead to distinctive phenotypes in recipient mice. Better standardisation of FMT experiments is needed to ensure reproducible and translatable results.

Abstract Hepatocyte nuclear factor-4α (Hnf4α) is a transcription factor that controls epithelial cell polarity and morphogenesis. Hnf4α conditional deletion during postnatal development has minor effects on intestinal epithelium integrity but promotes activation of the Wnt/β-catenin pathway without causing tumorigenesis. Here, we show that Hnf4α does not act as a tumor-suppressor gene but is crucial in promoting gut tumorigenesis in mice. Polyp multiplicity in ApcMin mice lacking Hnf4α is suppressed compared with littermate ApcMin controls. Analysis of microarray gene expression profiles from mice lacking Hnf4α in the intestinal epithelium identifies novel functions of this transcription factor in targeting oxidoreductase-related genes involved in the regulation of reactive oxygen species (ROS) levels. This role is supported with the demonstration that HNF4α is functionally involved in the protection against spontaneous and 5-fluorouracil chemotherapy-induced production of ROS in colorectal cancer cell lines. Analysis of a colorectal cancer patient cohort establishes that HNF4α is significantly upregulated compared with adjacent normal epithelial resections. Several genes involved in ROS neutralization are also induced in correlation with HNF4A expression. Altogether, the findings point to the nuclear receptor HNF4α as a potential therapeutic target to eradicate aberrant epithelial cell resistance to ROS production during intestinal tumorigenesis. Cancer Res; 70(22); 9423–33. ©2010 AACR.

Supplementary Figure 2 from Hepatocyte Nuclear Factor-4α Promotes Gut Neoplasia in Mice and Protects against the Production of Reactive Oxygen Species

While the prevalence of metabolic syndrome (MetS) is steadily increasing worldwide, no optimal pharmacotherapy is readily available to address its multifaceted risk factors and halt its complications. This growing challenge mandates the development of other future curative directions. The purpose of the present study is to investigate the efficacy of cranberry proanthocyanidins (PACs) in improving MetS pathological conditions and liver complications; C57BL/6J mice were fed either a standard chow or a high fat/high sucrose (HFHS) diet with and without PACs (200 mg/kg), delivered by daily gavage for 12 weeks. Our results show that PACs lowered HFHS-induced obesity, insulin resistance, and hyperlipidemia. In conjunction, PACs lessened circulatory markers of oxidative stress (OxS) and inflammation. Similarly, the anti-oxidative and anti-inflammatory capacities of PACs were noted in the liver in association with improved hepatic steatosis. Inhibition of lipogenesis and stimulation of beta-oxidation could account for PACs-mediated decline of fatty liver as evidenced not only by the expression of rate-limiting enzymes but also by the status of AMPKα (the key sensor of cellular energy) and the powerful transcription factors (PPARα, PGC1α, SREBP1c, ChREBP). Likewise, treatment with PACs resulted in the downregulation of critical enzymes of liver gluconeogenesis, a process contributing to increased rates of glucose production in type 2 diabetes. Our findings demonstrate that PACs prevented obesity and improved insulin resistance likely via suppression of OxS and inflammation while diminishing hyperlipidemia and fatty liver disease, as clear evidence for their strength of fighting the cluster of MetS abnormalities.

Supplementary Table 3 from Hepatocyte Nuclear Factor-4α Promotes Gut Neoplasia in Mice and Protects against the Production of Reactive Oxygen Species

Biallelic pathogenic variants of the Sar1b gene cause chylomicron retention disease (CRD) whose central phenotype is the inability to secrete chylomicrons. Patients with CRD experience numerous clinical symptoms such as gastrointestinal, hepatic, neuromuscular, ophthalmic, and cardiological abnormalities. Recently, the production of mice expressing either a targeted deletion or mutation of Sar1b recapitulated biochemical and gastrointestinal defects associated with CRD. The present study was conducted to better understand little-known aspects of Sar1b mutations, including mouse embryonic development, lipid profile, and lipoprotein composition in response to high-fat diet, gut and liver cholesterol metabolism, sex-specific effects, and genotype-phenotype differences. Sar1b deletion and mutation produce a lethal phenotype in homozygous mice, which display intestinal lipid accumulation without any gross morphological abnormalities. On high-fat diet, mutant mice exhibit more marked abnormalities in body composition, adipose tissue and liver weight, plasma cholesterol, non-HDL cholesterol and polyunsaturated fatty acids than those on the regular Chow diet. Divergences were also noted in lipoprotein lipid composition, lipid ratios (serving as indices of particle size) and lipoprotein-apolipoprotein distribution. Sar1b defects significantly reduce gut cholesterol accumulation while altering key players in cholesterol metabolism. Noteworthy, variations were observed between males and females, and between Sar1b deletion and mutation phenotypes. Overall, mutant animal findings reveal the importance of Sar1b in several biochemical, metabolic and developmental processes.

Milk-derived bioactive proteins have increasingly gained attention and consideration throughout the world due to their high-quality amino acids and multiple health-promoting attributes. Apparently, being at the forefront of functional foods, these bioactive proteins are also suggested as potential alternatives for the management of various complex diseases. In this review, we will focus on lactoferrin (LF) and osteopontin (OPN), two multifunctional dairy proteins, as well as to their naturally occurring bioactive LF–OPN complex. While describing their wide variety of physiological, biochemical, and nutritional functionalities, we will emphasize their specific roles in the perinatal period. Afterwards, we will evaluate their ability to control oxidative stress, inflammation, gut mucosal barrier, and intestinal microbiota in link with cardiometabolic disorders (CMD) (obesity, insulin resistance, dyslipidemia, and hypertension) and associated complications (diabetes and atherosclerosis). This review will not only attempt to highlight the mechanisms of action, but it will critically discuss the potential therapeutic applications of the underlined bioactive proteins in CMD.

Rationale and objectives: Acute lymphoblastic leukemia (ALL) is the most common pediatric cancer. Despite a 90% five-year survival rate, survivors of childhood ALL often suffer from late effects, including cardiometabolic disorders. Contributing factors such as inflammation and oxidative stress, combined with drug treatments, can induce premature aging and cellular senescence with a significant impact on cardiometabolic disorders. Premature aging can lead to decreased thymic T-cell production, resulting in decreased circulation of T-cell receptor excision circles (TRECs). Because diet has been associated with cardiometabolic disorders, we hypothesized that the quality of diet in children who had survived ALL was related to the immune aging biomarker TREC, in concert with inflammatory status. Methods: Adolescent and young adult survivors of pediatric ALL of the PETALE cohort (n=241, 22.1 ± 6.3 years at diagnosis, 49.4% male) were examined in their profile for TREC levels (by qPCR) and for adherence to 6 diet quality indices. Results: Adjusted linear regressions revealed that the Healthy Diet Indicator (HDI) was associated with TREC levels (β=50.0, p=0.005, adjusted p=0.03). After performing a conceptual relational analysis (CAR) for data mining of various biomarkers of inflammation, oxidative stress, endotoxemia, and endothelial or adipose dysfunction; interleukin-6 (IL-6) and C-reactive protein (CRP) were found to be negatively associated with TREC levels (β= -80 and -80.1, p=0.017 and 0.026, respectively) but not with HDI. Further analysis revealed that IL-6 and CRP levels were moderators, but not mediators, of the association between HDI and TREC. Conclusion: This study supports the positive impact of a healthy diet on premature immune aging and the moderating role of inflammation in this association. Citation Format: Abderrahim Benmoussa, Tibila Kientega, Sophia Morel, Guillaume Cardin, Sophie Bérard, Mickael wajnberg, Petko Valtchev, Alexandre Blondin-Masse, Daniel Curnier, Maja Krajinovic, Caroline Laverdière, Daniel Sinnett, Emile Levy, Sophie Marcoux, Francis Rodier, Valérie Marcil. Poor diet quality is associated with immune aging in survivors of pediatric acute lymphoblastic leukemia [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2003.

Abstract We compared endogenous ω-3 PUFA production to supplementation for improving obesity-related metabolic dysfunction. Fat-1 transgenic mice, who endogenously convert exogenous ω-6 to ω-3 PUFA, and wild-type littermates were fed a high-fat diet and a daily dose of either ω-3 or ω-6 PUFA-rich oil for 12 wk. The endogenous ω-3 PUFA production improved glucose intolerance and insulin resistance but not hepatic steatosis. Conversely, ω-3 PUFA supplementation fully prevented hepatic steatosis but failed to improve insulin resistance. Both models increased hepatic levels of ω-3 PUFA-containing 2-monoacylglycerol and N-acylethanolamine congeners, and reduced levels of ω-6 PUFA-derived endocannabinoids with ω-3 PUFA supplementation being more efficacious. Reduced hepatic lipid accumulation associated with the endocannabinoidome metabolites EPEA and DHEA, which was causally demonstrated by lower lipid accumulation in oleic acid-treated hepatic cells treated with these metabolites. While both models induced a significant fecal enrichment of the beneficial Allobaculum genus, mice supplemented with ω-3 PUFA displayed additional changes in the gut microbiota functions with a significant reduction of fecal levels of the proinflammatory molecules lipopolysaccharide and flagellin. Multiple-factor analysis identify that the metabolic improvements induced by ω-3 PUFAs were accompanied by a reduced production of the proinflammatory cytokine TNFα, and that ω-3 PUFA supplementation had a stronger effect on improving the hepatic fatty acid profile than endogenous ω-3 PUFA. While endogenous ω-3 PUFA production preferably improves glucose tolerance and insulin resistance, ω-3 PUFA intake appears to be required to elicit selective changes in hepatic endocannabinoidome signaling that are essential to alleviate high-fat diet-induced hepatic steatosis.

The consumption of plant-based bioactive compounds modulates the gut microbiota and interacts with the innate and adaptive immune responses associated with metabolic disorders. The present study aimed to evaluate the effect of cranberry polyphenols (CP), rich in flavonoids, and agavins (AG), a highly branched agave-derived neo-fructans, on cardiometabolic response, gut microbiota composition, metabolic endotoxemia, and mucosal immunomodulation of C57BL6 male mice fed an obesogenic high-fat and high-sucrose (HFHS) diet for 9 weeks. Interestingly, CP+AG-fed mice had improved glucose homeostasis. Oral supplementation with CP selectively and robustly (five-fold) increases the relative abundance of Akkermansia muciniphila, a beneficial bacteria associated with metabolic health. AG, either alone or combined with CP (CP+AG), mainly stimulated the glycan-degrading bacteria Muribaculum intestinale, Faecalibaculum rodentium, Bacteroides uniformis, and Bacteroides acidifaciens. This increase of glycan-degrading bacteria was consistent with a significantly increased level of butyrate in obese mice receiving AG, as compared to untreated counterparts. CP+AG-supplemented HFHS-fed mice had significantly lower levels of plasma LBP than HFHS-fed controls, suggesting blunted metabolic endotoxemia and improved intestinal barrier function. Gut microbiota and derived metabolites interact with the immunological factors to improve intestinal epithelium barrier function. Oral administration of CP and AG to obese mice contributed to dampen the pro-inflammatory immune response through different signaling pathways. CP and AG, alone or combined, increased toll-like receptor (TLR)-2 (Tlr2) expression, while decreasing the expression of interleukin 1ß (ILß1) in obese mice. Moreover, AG selectively promoted the anti-inflammatory marker Foxp3, while CP increased the expression of NOD-like receptor family pyrin domain containing 6 (Nlrp6) inflammasome. The intestinal immune system was also shaped by dietary factor recognition. Indeed, the combination of CP+AG significantly increased the expression of aryl hydrocarbon receptors (Ahr). Altogether, both CP and AG can shape gut microbiota composition and regulate key mucosal markers involved in the repair of epithelial barrier integrity, thereby attenuating obesity-associated gut dysbiosis and metabolic inflammation and improving glucose homeostasis.

Lead Author's Financial Disclosures Nothing to disclose. Study Funding None. Background/Synopsis The Abetalipoproteinemia and Related Disorders Foundation (ABLRDF) is a nonprofit international organization established in 2019 comprised of patients with abetalipoproteinemia (ABL), familial hypobetalipoproteinemia (FHBL) and related hypobetalipoproteinemia disorders together with caregivers, researchers and medical professionals. Objective/Purpose To (i) underline ABLRDF's mission to increase awareness of ABL and other FHBL disorders, provide guidelines for lifelong medical care and facilitate access to specialized professionals, medical evaluations, and appropriate treatments; and (ii) highlight ABLRDF as an international medical advisory resource and advocate for improved access to affordable care. Methods The patients and caregivers within ABLRDF performed non-scientific polling via Facebook to identify and prioritize health related concerns. An international panel of experts assembled to address these concerns, analyze the literature, and propose clinical guidelines. Initially, the panel was composed of two groups, which produced written descriptions for the hypobetalipoproteinemia disorders assigned to them. These versions were combined and all panel members then critically read and critiqued the final manuscript. Results (1) Several challenges faced by patients and caregivers were identified. First, physician awareness of monogenic hypobetalipoproteinemia disorders is suboptimal and contributes to a delay in diagnosis, resulting in substandard treatment and associated morbidities. Second, patient access to fat-soluble vitamins is often compromised by cost and/or inadequate insurance coverage. Third, published guidelines for the clinical management of hypobetalipoproteinemia disorders throughout the lifespan, including the peripartum period, are insufficient. (2)We classified monogenic hypobetalipoproteinemia into two subgroups based on the specific mechanisms that contribute to their disorders (Table 1). Class 1 disorders arise from defects in lipoprotein assembly and secretion. Class 2 disorders are due to enhanced lipoprotein catabolism. (3) We detailed the pathophysiology and clinical presentation of familial hypobetalipoproteinemia disorders and proposed guidelines for their lifelong management (Table 2). (4) Letters of medical necessity were submitted to insurance companies advocating coverage of fat-soluble vitamins for patients. Conclusions The real-world experience of individuals within ABLRDF provides a closer examination of the unique struggle in managing these complex disorders while affording an opportunity to elevate the standard of medical care. We provide guidance in the identification and management of familial hypobetalipoproteinemia disorders with an aim to improve the health-related quality of life for patients.

Intima-media thickness is a known subclinical radiologic marker of the early manifestations of atherosclerotic disease. It is the thickness of the vessel wall, most often the carotid artery. Intima-media thickness is measured on conventional US manually or automatically. Other measurement techniques include radiofrequency US. Because there is variation in its measurement, especially in children, several recommendations have been set to increase the measurement’s validity and comparability among studies. Despite these recommendations, several pitfalls should be avoided, and quality control should be performed to avoid erroneous interpretation. This article summarizes current literature in relation to the clinical applications for intima-media thickness measurement in children with known risk factors such as obesity, liver steatosis, hypercholesterolemia, diabetes, hypertension, systemic inflammatory diseases, cancer survival, kidney and liver transplant, and sickle cell disease or beta thalassemia major. Most potential indications for intima-media thickness measurement remain in the research domain and should be interpreted combined with other markers. The objective of diagnosing an increased intima-media thickness is to start a multidisciplinary treatment approach to prevent disease progression and its sequelae in adulthood.