Early Onset Research Articles

Temporal Trends in Racial and Gender Disparities of Early Onset Colorectal Cancer in the United States: An Analysis of the CDC WONDER Database.

The mortality rates of early-onset colorectal cancer (EOCRC) have surged globally over the past two decades. While the underlying reasons remain largely unknown, understanding its epidemiology is crucial to address this escalating trend. This study aimed to identify disparities potentially influencing these rates, enhancing risk assessment tools, and highlighting areas necessitating further research. Using the CDC Wide-Ranging Online Data for Epidemiologic Research (WONDER) database, this study assessed EOCRC mortality data from 2012 to 2020. Individuals under 50years who succumbed to EOCRC were identified through the International Classification of Diseases, Tenth Revision (ICD-10) codes. Data interpretation and representation were performed using R 4.2.2 software. Between 2012 and 2020, EOCRC mortality rates fluctuated marginally between 1.7 and 1.8 per 100,000. Male mortality rates increased from 1.9 to 2.0 per 100,000, while female rates varied between 1.5 and 1.6 per 100,000. Significant variations were observed across age groups, with the 40-49years category experiencing an increase from 6.34 (2012) to 6.94 (2020) per 100,000. Racial category-based data revealed the highest mortality rates among African Americans. Geographically, Mississippi and Alabama exhibited elevated mortality rates. Age-adjusted mortality rate (AAMR) assessments indicated a marked decline for both genders from 2012 to 2020, with consistently higher rates for men. The findings highlight the evolving landscape of EOCRC mortality, revealing significant gender, age, and racial disparities. These results underscore the urgent need for tailored health strategies and intensified research efforts targeting these disparities.

S431 Association Between Ring Finger Protein 213 (RNF213) Mutation and Increased Risk of Early Onset Colorectal Cancer

S431 Association Between Ring Finger Protein 213 (RNF213) Mutation and Increased Risk of Early Onset Colorectal Cancer

Heterozygous DSP in-frame deletion in a poodle with syndromic ichthyosis involving additional hair and tooth abnormalities.

Ichthyoses comprise a large heterogeneous group of skin disorders, characterized by generalized scaly and hyperkeratotic skin. We investigated a miniature poodle with early onset generalized scaling, dry and irregularly thickened skin, paw pad hyperkeratosis and abnormalities in hair and teeth. The clinical signs of ichthyosis were confirmed by histopathological examination, which revealed mild epidermal hyperplasia and lamellar orthokeratotic hyperkeratosis. A hereditary condition was suspected and a genetic investigation was initiated. We sequenced the whole genome of the affected dog and searched for potentially causative variants in functional candidate genes for the observed phenotype. The analysis revealed a heterozygous in-frame deletion in DSP, NC_049256.1:g.8804542_8804544del resulting from a de novo mutation event as evidenced by genotyping leukocyte DNA from both parents. The 3 bp deletion is predicted to remove one aspartic acid without disrupting the open reading frame (XM_038584124.1:c.1821_1823del, XP_038440052.1:p.(Asp608del)). The DSP gene encodes desmoplakin, a desmosomal plaque protein, responsible for cell-cell adhesion to provide resistance to mechanical stress in epidermal and cardiac tissues. We hypothesize that the deletion of one amino acid in the N-terminal globular head domain acts in a dominant negative manner and thus impairs the proper connection with other proteins. Several variants in DSP in humans and cattle have been described to result in different phenotypes associated with hair and skin abnormalities, sometimes in combination with variable cardiac and/or dental manifestations. In conclusion, we characterized a new syndromic ichthyosis phenotype in a dog and identified a de novo 3 bp deletion in the DSP gene as causal variant.

Development and Validation of a Preclinical Canine Model for Early Onset Fracture-Related Infections

Development and Validation of a Preclinical Canine Model for Early Onset Fracture-Related Infections

S453 Clinical Outcomes for Female Patients With Early Onset Colorectal Cancer: An Analysis of the National Inpatient Sample

S453 Clinical Outcomes for Female Patients With Early Onset Colorectal Cancer: An Analysis of the National Inpatient Sample

150P Patient, caregiver and healthcare professionals’ perspective on spinal bracing in early onset spinal muscular atrophy in the UK: a national survey

150P Patient, caregiver and healthcare professionals’ perspective on spinal bracing in early onset spinal muscular atrophy in the UK: a national survey

S5093 A Case of Early Onset Y-90 Radiation-Induced Gastritis

S5093 A Case of Early Onset Y-90 Radiation-Induced Gastritis

Persons Who Have Undergone ACL Reconstruction Exhibit Altered Patellofemoral Joint Contact Area: Implications For Early Onset Patellofemoral Joint Arthritis

Persons Who Have Undergone ACL Reconstruction Exhibit Altered Patellofemoral Joint Contact Area: Implications For Early Onset Patellofemoral Joint Arthritis

The Relationship Between Breast Radiation Dermatitis and Post-Mastectomy Chronic Pain: A Multicenter Retrospective Study

ObjectiveWith the increasing incidence of breast cancer, radiotherapy has become a crucial component of postoperative treatment to mitigate recurrence and metastasis. However, breast radiation dermatitis (BRD) and post-mastectomy pain syndrome (PMPS) remain significant complications, affecting patients' quality of life. Despite the importance of these issues, there is a lack of comprehensive studies exploring the correlation between BRD and PMPS, as well as effective management strategies for these conditions. MethodsThis multicenter retrospective study included 784 patients who underwent breast cancer surgery followed by radiotherapy between 2017 and 2023. Clinical data were collected from four major hospitals in China. Patients were assessed for BRD and PMPS using questionnaires and clinical records. ResultsBRD incidence was 81.25%, with elderly (average age 50.77 years) and obese patients (26.4% with BMI > 30) showing higher susceptibility. 23.4% of BRD patients developed PMPS, compared to 13.6% in the non-BRD group (P = 0.009). Early onset of BRD during radiotherapy (P =0.004) and larger affected areas (P =0.000) were linked to higher PMPS risk. ConclusionsThis study underscores the significant relationship between BRD and PMPS, emphasizing the need for targeted prevention and management strategies. The findings suggest that early intervention and personalized treatment plans are crucial for managing BRD and preventing PMPS.

Very early onset versus pediatric onset inflammatory bowel disease: a prospective cohort analysis

Very early onset versus pediatric onset inflammatory bowel disease: a prospective cohort analysis

Early-Onset Graham-Little-Piccardi-Lasseur Syndrome with Cutaneous Lichen Planus – A Rare Case Report and Review of Literature

Graham-Little-Piccardi-Lasseur syndrome (GLPLS) is a rare condition characterized by lichen planopilaris with scarring alopecia of the scalp and nonscarring alopecia of the axilla, groin, and pubis with keratosis pilaris. It usually affects middle-aged women more than men. The onset of scarring alopecia is usually reported in middle age. We report a case of GLPLS from South India, having early onset of alopecia in childhood, associated with cutaneous lichen planus.

Refining criteria for a neurodevelopmental sub-phenotype of bipolar disorders: a FondaMental Advanced Centers of Expertise for Bipolar Disorders study

Bipolar disorder (BD) is a complex and heterogeneous psychiatric disorder. Neurodevelopmental factors were suggested to contribute to the etiology of BD, yet a specific neurodevelopmental phenotype of the disorder remains unidentified. Our objective was to define and characterize a neurodevelopmental phenotype (NDP) in BD and validate its associations with clinical outcomes, polygenic risk scores (PGS), and treatment responses. We analyzed the FACE-BD cohort of 4,468 BD patients, a validation cohort of 101 BD patients, and two independent replication datasets of 274 and 89 BD patients. Using factor analyses, we identified a set of criteria for defining NDP. We next developed a scoring system for NDP-load and assessed its association with prognosis, neurological soft signs, polygenic risk scores for neurodevelopmental disorders, and responses to treatment using multiple regressions, adjusted for age and sex with bootstrap replications. Our study established a NDP in BD consisting of nine clinical features: advanced paternal age, advanced maternal age, childhood maltreatment, attention deficit hyperactivity disorder (ADHD), early onset of BD, early onset of substance use disorders, early onset of anxiety disorders, early onset of eating disorders, specific learning disorders. Patients with higher NDP-load showed a worse prognosis and increased neurological soft signs. Notably, these individuals exhibited a poorer response to lithium treatment. Furthermore, a significant positive correlation was observed between the NDP-load and PGS for ADHD suggesting potential overlapping genetic factors or pathophysiological mechanisms between BD and ADHD. The proposed NDP constitutes a promising clinical tool for patient stratification in BD.

The Role of Inducible Nitric Oxide Synthase in Assessing the Functional Level of Coronary Artery Lesions in Chronic Coronary Syndrome.

Chronic coronary syndrome (CCS) is a long-term manifestation of coronary artery disease, marked by stable but recurring chest pain and myocardial ischemia due to the gradual buildup of atherosclerotic plaques in the coronary arteries. It is a metabolic disorder of coronary arteries characterized by oxidative stress, endothelial dysfunction, inflammation, and hyperlipidemia. The imbalance in oxidative-antioxidative status contributes to stable ischemic heart disease. Oxidative stress involves reactive oxygen and nitrogen species, leading to low-density lipoprotein (LDL) oxidation. Endothelial dysfunction, marked by reduced nitric oxide (NO) bioavailability, is an early onset of CCS, affecting vasodilation, cell proliferation, and inflammatory responses. Enzyme myeloperoxidase (MPO), traditionally considered protective, plays a dual role in initiating and progressing inflammatory diseases. MPO interacts with NO, modulating its catalytic activity. Elevated NO levels inhibit MPO through a reversible complex formation, preventing NO-induced inhibition by inducible nitric oxide synthase (iNOS). MPO also inactivates endothelial nitric oxide synthase (eNOS) and reacts with L-arginine, hindering NO synthesis. The interplay between MPO and NO significantly influences inflammation sites, impacting peroxidation rates and oxidation reactions. Peroxynitrite, a reactive species, contributes to nitration of tyrosine residues and lipid peroxidation. Mechanistic pathways suggest MPO enhances iNOS catalytic activity, influencing CCS development. iNOS, implicated in inflammation and atherosclerosis, is connected to NO regulation. This review analyzes the complex interplay of MPO, iNOS, and NO that affects plaque morphology, oxidative stress, and inflammation, contributing to atherosclerosis progression. Therefore, it is possible that the phenotypes of atherosclerotic plaques, focal and diffuse coronary artery disease, could be defined by the relationship between MPO and iNOS.

S455 Clinical Outcomes for Patients With Hyperlipidemia and Early Onset Colorectal Cancer: An Analysis of the National Inpatient Sample

S455 Clinical Outcomes for Patients With Hyperlipidemia and Early Onset Colorectal Cancer: An Analysis of the National Inpatient Sample

Genotype/phenotype correlations in multiple endocrine neoplasia type 2.

Multiple endocrine neoplasia type 2 (MEN 2) is a rare hereditary endocrine tumour syndrome caused by mutations in the rearranged during transfection (RET) gene. MEN 2 is divided into two main entities, MEN 2A and MEN2B, both of which present with medullary thyroid cancer (MTC) in approximately 100% of cases and pheochromocytoma in 50% of cases. Specific RET mutations are associated with a risk of early onset of MTC, from 1 year of age (highest risk) to 5 years of age (high risk). This risk defines the optimal timing for thyroidectomy, ideally at an age when the disease has not spread. This is the most important genotype-phenotype correlation observed in MEN 2. Specific RET mutations also define the penetrance of pheochromocytoma. However, despite the presence of these highest/high risk variants, some patients unexpectedly present with non-aggressive MTC or never present with pheochromocytoma, suggesting that factors other than the major RET variant may modify the natural history and genotype-phenotype correlations. Improving our understanding of the genotype-phenotype correlations would allow individualizing the management and follow-up of patients with MEN 2. The aim of this brief review is to discuss the main genotype-phenotype correlations in MEN 2 and the potential factors that might influence these correlations.

S159 Survival Analysis of Early Onset Pancreatic Cancer: A SEER study (2016-2021)

S159 Survival Analysis of Early Onset Pancreatic Cancer: A SEER study (2016-2021)

Identifying clinical and proteomic markers for early diagnosis and prognosis prediction of major psychiatric disorders

BackgroundTo clarify if blood proteins can predict disease progression among individuals at clinical high-risk of severe mental illness (CHR-SMI), we developed a statistical model incorporating clinical and blood protein markers to distinguish the transition group (who developed severe mental illness) (CHR-SMI-T) and from non-transition group (CHR-SMI-NT) at baseline. MethodsNinety individuals (74 at CHR-SMI: 16 patients) were monitored for ≤4 years and were the focus of predictive models. Three predictive models (1 [100 clinical variables], 2 [158 peptides], and 3 [100 clinical variables +158 peptides]) were evaluated using area under the receiver operating characteristic (AUROC) values. Clinical and protein feature patterns were evaluated by linear mixed-effect analysis within the model at 12 and 24 months among patients who did (CHR-SMI-T) and did not transition (CHR-SMI-NT) and the entire group. ResultEighteen CHR-SMI individuals with major psychiatric disorders (first episode psychosis: 2; bipolar II disorder: 13; major depressive disorder; 3) developed disorders over an average of 17.7 months. The combined model showed the highest discriminatory performance (AUROC = 0.73). Cytosolic malate dehydrogenase and transgelin-2 levels were lower in the CHR-SMI-T than the CHR-SMI-NT group. Complement component C9, inter-alpha-trypsin inhibitor heavy chain H4, von Willebrand factor, and C-reactive protein were lower in the patient than the CHR-SMI-NT group. These differences were non-significant after FDR adjustment. LimitationsSmall sample, no control for medication use. ConclusionThis exploratory study identified clinical and proteomic markers that might predict severe mental illness early onset, which could aid in early detection and intervention. Future studies with larger samples and controlled variables are needed to validate these findings.

Chronic low-grade inflammation associated with higher risk and earlier onset of cardiometabolic multimorbidity in middle-aged and older adults: a population-based cohort study.

Evidence regarding the role of chronic low-grade inflammation in the progression of cardiometabolic diseases (CMDs) and cardiometabolic multimorbidity (CMM) is currently limited. This prospective cohort study, utilising data from the UK Biobank, included 273,804 adults aged 40-69years initially free of CMD at baseline. CMM was defined as the coexistence of two or more CMDs, such as coronary artery disease, type 2 diabetes mellitus, hypertension and stroke. The aggregated inflammation score (INFLA-score), incorporating C-reactive protein, white blood cell count, platelet count and granulocyte-to-lymphocyte ratio, quantified chronic low-grade inflammation. Absolute risks (ARs), hazard ratios (HRs) and 95% confidence intervals (CIs) assessed the association of increased INFLA-score with the risk of CMMs and CMDs. The accelerated failure time model explored the effect of INFLA-score on the time to CMM onset, and a restricted cubic spline characterised the dose-dependent relationship between INFLA-score and CMM risk. After a median follow-up of 166.37months, 13,755 cases of CMM were identified. In quartiles with increasing INFLA-score levels, CMM ARs were 4.41%, 4.49%, 5.04% and 6.01%, respectively; HR increased by 2%, 15% and 36%, respectively, compared to the lowest quartile. The INFLA-score and CMM risk relationship was nonlinear (P for nonlinear < 0.001), exhibiting a significant risk trend change at a score of 9. For INFLA-score < 9, CMM risk increased by 1.9% for each 1-point increase; for INFLA-score ≥ 9, the risk increased by 5.9% for each 1-point increase. Additionally, a higher INFLA-score was associated with an earlier onset of CMM (P < 0.001). Compared to the first INFLA-score quartile, the AFT model revealed adjusted median times to CMM occurrence were 2.92, 6.10 and 13.19months earlier in the second, third and fourth quartile groups, respectively. Chronic low-grade inflammation is associated with a higher risk of cardiometabolic multimorbidity and earlier onset among middle-aged and older adults. Monitoring and screening the INFLA-score in adults without CMDs may improve early prevention of CMM.

Impact of BMI on childhood growth, pubertal timing, and bone maturation: A comprehensive review and clinical implications

Introduction: Childhood obesity and undernutrition significantly affect growth patterns, pubertal timing, and bone maturation, leading to long-term health implications. Materials and Methods: A comprehensive literature review was conducted using databases such as PubMed, Google Scholar, and Scopus. Twenty-four studies, including a total of 40,732 patients, were analyzed from two tables examining the impact of BMI, growth patterns, pubertal timing, and bone maturation. Results: Children with high BMI exhibit accelerated linear growth during early childhood, that may be driven by elevated leptin levels, which stimulate growth before puberty. Despite early growth advantages, these children experience reduced height gain during adolescence due to advanced bone maturation and earlier closure of growth plates. High BMI is strongly linked to early puberty, especially in girls, as increased adipose tissue raises leptin levels, triggering early pubertal onset. Boys, however, show variability in pubertal timing, with severe obesity sometimes delaying puberty. In contrast, children with low BMI or undernutrition demonstrate delayed linear growth and delayed puberty. Nutritional deficits lead to reduced growth velocity, delayed pubertal onset, and extended pubertal periods due to a lack of adipose tissue and hormonal deficiencies in leptin and kisspeptin. Nutritional rehabilitation promotes catch-up growth, allowing for extended growth potential by delaying growth plate closure. However, full recovery may not occur in cases of prolonged or severe undernutrition. Advanced bone age in high BMI children shortens the pubertal growth spurt, while delayed bone maturation in undernourished children offers a prolonged period for potential growth, contingent on timely nutritional support. Conclusion: Timely interventions for childhood obesity and undernutrition are critical to improving growth outcomes and preventing long-term developmental delays. Early identification, nutritional rehabilitation, and lifestyle modifications can help optimize growth and pubertal development by addressing both advanced and delayed growth trajectories.

CHILDHOOD SEXUAL ABUSE IMPACT ON ADULTHOOD

Introduction – Child sexual abuse (CSA) occurs when a kid or younger person is forced or persuaded to engage in sexual activity, whether the child is conscious of what is taking place. According to global databases, in one-third of countries in the world, at least 5% of young women reported experiences of sexual abuse in childhood. Mental health issues, behavioral manifestations, and interpersonal outcomes are a few impacts of CSA. This study aims to discuss the CSA's impact on adulthood. Methods – The researcher used a total of 13 works of literature, articles, and journals that discuss CSA and its correlation with some mental health issues impact on an adult. Results – Adults with a history of CSA are more likely to suffer from early onset depression, borderline personality disorder, and suicidal tendencies than someone without a history, that is why emotional support seems very important to the CSA survivors. Discuss – As children are sexually abused, it may lead to a variety of difficulties with relationships in general, as well as a host of poor intimate relationship consequences such as adult sexual assault, intimate partner violence, and reduced happiness in romantic relationships. Conclusion – Childhood sexual abuse is still a major problem among children and has several psychological impacts on adulthood, and emotional support is one of the great therapies. Keywords: childhood, sexual, abuse.