Ashraf Tawfik Soliman

The heart is increasingly recognised as a cardiovascular signalling organ that releases biologically active natriuretic peptides during haemodynamic stress. In cyanotic CHD, chronic hypoxaemia, altered loading conditions, increased energy expenditure, recurrent illness, and delayed repair may disrupt endocrine, metabolic, and nutritional pathways that regulate growth. This structured narrative review synthesises evidence linking cardiac biomarkers, systemic hormonal adaptation, nutritional status, surgical timing, and growth outcomes in children with cyanotic CHD. PubMed, Scopus, and Google Scholar were searched for human studies published from January 1990 to December 2025 that reported cardiac biomarkers, systemic hormonal measures, growth parameters, nutritional outcomes, or postoperative recovery in paediatric CHD. Thirty-six studies were included and narratively synthesised because lesion types, age groups, assays, and outcomes were heterogeneous. The evidence indicates consistent activation of natriuretic peptide signalling, reduced circulating insulin-like growth factor 1 and insulin-like growth factor binding protein 3 in several paediatric cohorts, appetite-related hormonal changes, impaired weight gain, and frequent linear growth faltering. Longitudinal studies suggest partial improvement in growth velocity and anabolic signalling after timely surgical correction, although incomplete recovery may occur when preoperative hypoxaemia and undernutrition are prolonged. Growth failure in cyanotic CHD should therefore be regarded as a multifactorial cardiovascular-nutritional syndrome rather than isolated primary endocrine disease. Early surgical referral, individualised nutrition, and coordinated cardiology, endocrinology, and dietetic follow-up are central to improving long-term outcomes.

Age-associated endocrine change is frequently described in the language of deficiency, yet a lower circulating hormone concentration does not necessarily establish disease or demonstrate that replacement will improve health. This critical narrative review examines the growth hormone–insulin-like growth factor-1, thyroid, gonadal and adrenal axes, focusing on the distinction between adaptive remodelling, pathological endocrine failure and potentially reversible effects of illness, adiposity, medication and altered feedback. Peer-reviewed observational studies, randomised trials, evidence syntheses and professional guidance were examined alongside developmental endocrinology literature, with evidence considered up to 23 August 2026. Across the four axes, the clinical implications of similar age-associated laboratory changes are strikingly different. Reduced somatotropic signalling may entail trade-offs between growth, metabolic maintenance and disease resistance, while growth hormone administration to otherwise healthy older adults has not shown compelling functional benefit. Mild thyrotropin elevation in later life often occurs without low free thyroxine, and trials have not demonstrated meaningful average symptomatic gains from routine levothyroxine in older adults with mild subclinical hypothyroidism. Ovarian menopause is a distinctive physiological transition for which hormone therapy may provide important symptom and skeletal benefits in appropriately selected individuals, whereas testosterone treatment requires biochemical and clinical evidence of hypogonadism and careful monitoring. Adrenal androgen decline is not equivalent to adrenal insufficiency, and replacement studies do not support indiscriminate use of dehydroepiandrosterone for healthy ageing. Developmental comparisons show why the same hormone concentration can represent normality, disease or treatment response at different life stages. A clinical decision framework is proposed that weighs trajectory, symptoms, feedback integrity, functional outcomes and intervention evidence rather than chronological age or a single assay result. Future studies should prioritise longitudinal within-person measurements, age-sensitive reference intervals, functional outcomes and life-course follow-up. Endocrine ageing is best understood as heterogeneous remodelling with discrete, clinically important exceptions requiring targeted treatment.

Introduction: Childhood obesity drives nonalcoholic fatty liver disease (NAFLD) and adipokine dysregulation, converging on insulin resistance (IR) to promote subclinical vascular injury measurable as increased carotid intima–media thickness (cIMT). Pediatric-specific mechanistic integration of these pathways with early atherosclerosis remains incompletely characterized. This review synthesizes evidence on NAFLD severity and cIMT in obese youth, examines the roles of resistin, high-molecular-weight (HMW) adiponectin, chemerin, and inflammatory mediators in IR-driven vascular remodeling, and evaluates their diagnostic and therapeutic implications. Content: A structured narrative review following SANRA guidance was conducted. PubMed/MEDLINE was searched from January 2000 to March 2025 for studies enrolling children aged 2–18 years with obesity and reporting cIMT measured by B-mode ultrasonography alongside NAFLD or adipokine measures. Quality was assessed using the Newcastle–Ottawa Scale (NOS) and AMSTAR-2. Across ten included studies (NOS scores: 5–8/9), obese children with NAFLD demonstrated consistently higher cIMT than controls (pooled weighted mean difference: +0.06 mm; 95% CI: 0.04–0.08 mm). Biopsy-proven nonalcoholic steatohepatitis independently predicted greater cIMT than simple steatosis (r=0.41; p<0.01). Resistin showed the strongest adipokine–cIMT association (r=0.47; p<0.001), with direct (β=0.31) and indirect effects via HOMA-IR (β=0.18) and high-sensitivity C-reactive protein (β=0.12). HMW-adiponectin deficiency, rather than total adiponectin, defined the preatherosclerotic phenotype. Chemerin correlated with cIMT (r=0.44; p<0.01) and metabolic syndrome score (β=0.39; p<0.001). Weight-loss intervention reduced cIMT by 0.03 mm (p<0.05), accompanied by adipokine normalization. Summary and Outlook: NAFLD and adipokine dysregulation constitute interdigitated, IR-centered pathways associated with early atherosclerosis in obese youth, detectable from age 7 and partially reversible with timely intervention. A tiered algorithm incorporating BMI, liver enzymes, HOMA-IR, cIMT, and adipokine profiling is proposed for clinical risk stratification.

Soil-transmitted helminth (STH) infections remain concentrated in children living in settings where poverty, inadequate sanitation, recurrent enteric infection and undernutrition overlap. This convergence has encouraged a long-standing expectation that deworming should improve weight gain and linear growth. Yet the growth evidence is heterogeneous, and the biological pathway connecting worm clearance to somatic growth has rarely been examined directly. This critical narrative review evaluates evidence on Ascaris lumbricoides, Trichuris trichiura and hookworm infections, focusing on weight gain, height or length gain, and the growth hormone–insulin-like growth factor-1 (GH–IGF-1) axis. Literature was identified through PubMed, Europe PMC, OpenAlex, DOAJ, Semantic Scholar, Google Scholar, WHO resources and citation searching, with the principal search period extending to 8 August 2026 and older foundational studies retained where necessary. Randomised trials from high-intensity infection settings reported short-term improvements in weight and occasionally height after anthelminthic treatment, whereas larger and more recent population-level trials and evidence syntheses generally found little or no average effect of repeated mass deworming on weight or linear growth. The contrast is biologically plausible rather than necessarily contradictory: benefit is most likely when infection intensity is sufficient to impair appetite, nutrient utilisation, intestinal function, iron status or inflammatory homeostasis, and when these constraints are reversible within the observation period. Evidence linking STH infection specifically to the GH–IGF-1 axis is sparse. The strongest helminth-specific endocrine observations derive from Trichuris dysentery syndrome, where low IGF-1 and impaired collagen synthesis improved during recovery. Broader paediatric evidence shows that undernutrition, intestinal dysfunction and systemic inflammation can suppress IGF-1 signalling and linear growth. Current data therefore support a conditional model in which deworming removes one growth constraint but does not reliably overcome coexisting dietary, inflammatory and environmental constraints. Future trials should measure infection intensity, diet, inflammation, enteric dysfunction, IGF-1/IGFBP-3 and growth velocity together, enabling identification of children in whom parasite clearance can produce meaningful catch-up growth.

Longitudinal bone growth in children depends on endochondral ossification within the epiphyseal growth plate, a process long viewed as a passive readout of systemic hormones but now recognized as an actively regulated, self-limiting process. This mini-review synthesizes recent evidence on chondrocyte biology, growth plate senescence, and the growth hormone (GH)–insulin-like growth factor 1 (IGF-1) axis. Local paracrine networks establish precise antagonistic and synergistic interactions: fibroblast growth factor receptor 3 (FGFR3) suppresses chondrocyte proliferation via MAPK/STAT signaling, while the C-type natriuretic peptide/NPR2 pathway counters this via cGMP-mediated stimulation; the Indian hedgehog–parathyroid hormone–related protein feedback loop, the SHOX gene, and mechanical loading provide additional structural control. Growth plate senescence follows a proposed localized, cell-counting mechanism reflecting cumulative chondrocyte division that current evidence supports but that has not been established as the sole explanation for chronological variation in physeal closure. Estrogen is a key accelerant of this senescent process during puberty. Pathogenic variants in these local regulators underlie conditions such as achondroplasia and a minority of cases classified as idiopathic short stature, and mechanism-targeted therapies – including vosoritide, a C-type natriuretic peptide analog, together with the FGFR3-directed tyrosine kinase inhibitor infigratinib and the once-weekly CNP prodrug navepegritide – illustrate, for achondroplasia specifically, how targeting a defined paracrine lesion can produce growth responses that systemic hormone stimulation alone does not achieve in that disorder. For a limited group of monogenic growth-plate disorders, resolving these molecular networks is beginning to complement uniform systemic intervention with precision, mechanism-based therapy, although this paradigm remains investigational for the great majority of children with short stature.

Diabetic kidney disease is a major long-term complication of diabetes, with renal injury potentially beginning during childhood or adolescence. This narrative review compares the prevalence, onset, and progression of early renal abnormalities in youth-onset type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM), and summarizes underlying mechanisms and renoprotective strategies. Thirty-nine PubMed-indexed publications met the inclusion criteria. Compared with T1DM, youth-onset T2DM was associated with earlier and more frequent albuminuria, approximately threefold higher hypertension prevalence by early adulthood, earlier hyperfiltration, and nearly twice the cumulative burden of overt diabetic kidney disease by the third decade of life. In T1DM, renal injury is driven mainly by hyperglycemia-related hemodynamic and tubuloglomerular disturbances, whereas in T2DM it is amplified by insulin resistance, visceral adiposity, dyslipidemia, hyperuricemia, and inflammation. Renoprotective strategies include intensive glycemic control, renin-angiotensin system blockade, sodium-glucose cotransporter 2 inhibitors, glucagon-like peptide-1 receptor agonists, and metabolic interventions. Early surveillance for albuminuria, hypertension, and hyperfiltration is warranted in both groups, with particular urgency in youth-onset T2DM.

Amino Acid Pattern Signatures in Pediatric Obesity, Dysglycemia, and Fatty Liver Disease: Links to Insulin Resistance and the IGF-1 Axis - The Journal of Pediatric Research

Childhood and adolescent obesity is strongly associated with an atherogenic lipid profile and silent cardiovascular injury that begins early and evolves over time. In this structured review, we synthesized PubMed-indexed evidence from the past 25 years on lipid profile changes in children and adolescents with varying degrees of obesity- overweight, obesity, and severe obesity-and their cardiovascular consequences from childhood through young adulthood, as well as interventions that improve lipid profile and cardiovascular risk. Obesity-related dyslipidemia consistently involves elevated triglyceride, reduced high-density lipoprotein cholesterol (HDL-C), and elevated non-HDL-C levels, as well as increased triglyceride/ HDL-C ratio, whereas low-density lipoprotein cholesterol levels, although clinically important, are less consistently abnormal; the burden rises with obesity severity. In childhood, this pattern manifests with subclinical endothelial dysfunction and early carotid intimal thickening; during adolescence, arterial stiffness, elevated blood pressure levels, and early left ventricular remodeling with diastolic dysfunction become detectable, particularly in severe obesity; by young adulthood, these changes progress into accelerated atherosclerosis and clinical car diovascular risk. Mechanistically, visceral adiposity increases free fatty acid flux and promotes hepatic very-lowdensity lipoprotein overproduction, while adipose tissue inflammation, low adiponectin levels, oxidative stress, and impaired nitric oxide bioavailability link the lipid profile to vascular and cardiac injury through insulin resistance. Lifestyle interventions and improving physical fitness and dietary quality remain first-line treatments. Antiobesity pharmacotherapy and metabolic-bariatric surgery can improve weight and cardiometabolic risk in selected adolescents with severe obesity, but long-term pediatric cardiovascular outcome data remain limited. Routine lipid profile screening combined with blood pressure, insulin resistance, and obesity severity assessments should be integrated with early, family-centered intervention to reduce lifelong cardiovascular risk.