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Background: The medial temporal lobe (MTL) is hypothesized to be relatively spared in early-onset Alzheimer's disease (EOAD). Yet, detailed examination of MTL subfields and drivers of atrophy in amnestic EOAD is lacking. Methods: BioFINDER-2 participants with memory impairment, abnormal amyloid-β and tau-PET were included. Forty-one amnestic EOAD individuals ≤65 years and, as comparison, late-onset AD (aLOAD, ≥70 years, n = 154) and amyloid-β-negative cognitively unimpaired controls were included. MTL subregions and biomarkers of (co-)pathologies were measured. Results: AD groups showed smaller MTL subregions compared to controls. Atrophy patterns were similar across AD groups: aLOAD showed thinner entorhinal cortices than aEOAD; aEOAD showed thinner parietal regions than aLOAD. aEOAD showed lower white matter hyperintensities than aLOAD. No differences in MTL tau-PET or transactive response DNA binding protein 43-proxy positivity were found. Conclusions: We found evidence for MTL atrophy in amnestic EOAD and overall similar levels to aLOAD of MTL tau pathology and co-pathologies. [ABSTRACT FROM AUTHOR]

Spastic paraplegia type 3A (SPG3A) is the second most common form of hereditary spastic paraplegia (HSP). This autosomal-dominant-inherited motor disorder is caused by heterozygous variants in the ATL1 gene which usually presents as a pure childhood-onset spastic paraplegia. Affected individuals present muscle weakness and spasticity in the lower limbs, with symptom onset in the first decade of life. Individuals with SPG3A typically present a slow progression and remain ambulatory throughout their life. Here we report three unrelated individuals presenting with very-early-onset (before 7 months) complex, and severe HSP phenotypes (axial hypotonia, spastic quadriplegia, dystonia, seizures and intellectual disability). For 2 of the 3 patients, these phenotypes led to the initial diagnosis of cerebral palsy (CP). These individuals carried novel ATL1 pathogenic variants (a de novo ATL1 missense p.(Lys406Glu), a homozygous frameshift p.(Arg403Glufs*3) and a homozygous missense variant (p.Tyr367His)). The parents carrying the heterozygous frameshift and missense variants were asymptomatic. Through these observations, we increase the knowledge on genotype–phenotype correlations in SPG3A and offer additional proof for possible autosomal recessive forms of SPG3A, while raising awareness on these exceptional phenotypes. Their ability to mimic CP also implies that genetic testing should be considered for patients with atypical forms of CP, given the implications for genetic counseling. [ABSTRACT FROM AUTHOR]

This study aimed to assess the burden of early-onset gastrointestinal (GI) cancers in China over three decades. A comprehensive analysis was performed using data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019. Data on early-onset GI cancers in 2020 and from 1990 to 2019 were extracted from GLOBOCAN 2020 database and GBD 2019, respectively. The average annual percent change (AAPC) was calculated to analyze the temporal trends using the Joinpoint Regression Program. The Bayesian age-period-cohort (BAPC) model was used to predict future trends up to 2030. In China, there were 185,980 incident cases and 119,116 deaths of early-onset GI cancer in 2020, with the highest incidence and mortality observed in liver cancer (new cases: 71,662; deaths: 62,412). The spectrum of early-onset GI cancers in China has transitioned over the last 30 years. The age-standardized rates of incidence, mortality, and disability-adjusted life years for colorectal and pancreatic cancers exhibited rapid increases (AAPC >0, P ≤ 0.001). The fastest-growing incidence rate was found in colorectal cancer (AAPC: 3.06, P < 0.001). Despite the decreases in liver, gastric, and esophageal cancers, these trends have been reversed or flattened in recent years. High body mass index was found to be the fastest-growing risk factor for early-onset GI cancers (estimated annual percentage change: 2.75–4.19, P < 0.05). Projection analyses showed an increasing trend in age-standardized incidence rates for almost all early-onset GI cancers during 2020–2030. The transitioning pattern of early-onset GI cancers in China emphasizes the urgency of addressing this public health challenge. [ABSTRACT FROM AUTHOR]

The incidence and prevalence of type 2 diabetes mellitus (T2DM) in young individuals (aged <40 years) have significantly increased in recent years, approximating two to threefold increase in the respective rates. Numerous risk factors including severe obesity, family history, ethnicity, maternal diabetes or gestational diabetes, and female sex contribute to a younger age of onset. In terms of pathogenesis, impaired insulin secretion is the key operating mechanism, alongside with ectopic adiposity-related insulin resistance. T2DM diagnosis in a young adult requires the exclusion of type 1 diabetes mellitus (T1DM), latent autoimmune diabetes of adults (LADA) and maturity-onset diabetes of the young (MODY). The establishment of such diagnosis is critical for prognosis, because early-onset T2DM is associated with rapid deterioration in pancreatic β-cell secretory function leading to earlier initiation of insulin therapy. Furthermore, mortality and lifetime risk of developing complications, especially microvascular, is increased in these patients compared to both later-onset T2DM and T1DM patients; also, the latter are often developed earlier in the course of disease. The management of early-onset T2DM follows the same guidelines as in later-onset T2DM; yet patients aged 18–39 years are underrepresented in the big clinical trials on which the development of guidelines is based. Finally, young people with T2DM face significant challenges associated with social determinants, which compromise their adherence to therapy and induce diabetes distress. Future research focusing on the pathogenesis of β-cell decline and complications, as well as on specific treatment shall lead to better understanding and management of early-onset T2DM. [ABSTRACT FROM AUTHOR]

The characteristics of early-onset (onset age <50 years) and later-onset (onset age ≽ 50 years) cancers differ significantly. Identifying novel risk factors for both types of cancer is crucial for increasing awareness of cancer prevention and for reducing its burden. This study aimed to analyze the trends in incidence and risk factors for early-onset and late-onset cancers. We conducted a prospective study by drawing data from the Kailuan Study. This study included 6,741 participants with cancer (624 with early-onset cancer and 6,117 with later-onset cancer) and 6,780 matched controls among the 186,249 participants who underwent Kailuan health examinations from 2006 to 2019. The primary outcomes were cancer incidence rates, and associated risk factors for early- and later-onset cancer. Weighted Cox regression was used to calculate hazard ratios and 95% confidence intervals of each exposure factor for early- and later-onset cancer by cancer type. Population-attributable risk proportions were used to estimate the number of cases that could be prevented by eliminating a risk factor from the population. Except for liver cancer, incidence rates for nearly all types of cancer increased during the study period. Smoking, alcohol consumption, lipid metabolism disorders, hypertension, diabetes mellitus, fatty liver, and inflammation were associated with a significantly increased risk of cancer at multiple sites, but risk factors for cancer incidence differed by site. Smoking, alcohol consumption, inflammation, and hypertension were the major contributors to preventable cancer. The incidence of several different types of cancer, including early-onset cancer, is increasing in northeastern China. Differences in risk factors between early-onset and later-onset malignancies may contribute to the divergence in the observed changes in incidence trends between these two specific types of cancer. [ABSTRACT FROM AUTHOR]

Simple Summary: The incidence of colorectal cancer in people under 50 years old is rapidly increasing in the United States. Our study aims to understand how often early-onset colorectal cancer occurs and what factors contribute to its rise. By analyzing data from 1990 to 2021, we found a significant increase in cancer cases, especially among women and those born after 1983. Our findings highlight the need for targeted prevention strategies and further research to uncover the reasons behind these trends. This research can help the medical community develop better screening and prevention methods to reduce the incidence of early-onset colorectal cancer. The incidence of early-onset colorectal cancer (EO-CRC) in individuals under 50 years old is rapidly increasing in the United States. This study aims to evaluate EO-CRC incidence rates using data from the Global Burden of Disease Study (GBD) 2021, providing insights into trends from 1990 to 2021. We employed an age–period–cohort (APC) model analysis to estimate the effects of age, time period, and birth cohort on EO-CRC incidence. Our findings indicate that the number of EO-CRC cases rose from 6256 (95% UI: 6059–6456) in 1990 to 9311 (95% UI: 8859–9744) in 2021, a 49% increase from 1990 to 2021. The age-standardized incidence rate per 100,000 population increased by 34% during this period. The net drift in females (0.22%, 95% CI: 0.20–0.24) was slightly higher than in males (0.21%, 95% CI: 0.19–0.23) (p = 0.45). The APC analysis revealed that being over 25 years old, the period from 2005–2021, and being born after 1983 negatively impacted EO-CRC incidence rates, with a sharp rise after 2000 and a reduction among females from 2017 to 2021. Our study highlights the need for targeted prevention strategies and further research to understand these trends. [ABSTRACT FROM AUTHOR]

Background: Research is yet to elucidate adolescent polysubstance use profiles among youth with early-onset cannabis use (CU; ≤15 years). The present study aimed to fill this gap in the literature and determine whether CU outcomes in early adulthood are best explained by early-onset CU per se, or by its resulting polysubstance use profiles. Methods: Participants were N = 794 youth (56% females) from the Québec Longitudinal Study of Child Development, who reported lifetime CU by age 21. Participants were stratified into early-onset (n = 349), later adolescent-onset (16–18 years; n = 359), and adult-onset (≥19 years; n = 86) CU groups. Self-reported substance use was collected from the early-onset CU group at age 15 and 17, while CU frequency and problem CU were assessed for all participants at age 21. Results: Repeated measures latent profile analyses revealed four polysubstance use profiles among youth in the early-onset CU group: (1) light (54%); (2) escalating (13%); (3) frequent (without cigarettes; 14%); (4) frequent (with cigarettes; 19%). Only youth in the early-onset CU group who followed an escalating or frequent (with cigarettes) adolescent polysubstance use profile had consistently greater CU frequency and problem CU at 21 years, compared to youth in the later adolescent-onset (16–18 years), or adult-onset (≥19 years) CU groups (β range = 0.13 to.40; Cohen's f2 range = 0.02 to 0.12). Conclusions: Youth with early-onset CU are not a single homogenous group, but rather follow unique polysubstance use profiles that are differentially associated with risk for future problem CU. [ABSTRACT FROM AUTHOR]

Objective: We aimed to investigate the presence of monogenic causes of systemic lupus erythematosus (SLE) in our early-onset SLE patients. Methods: Fifteen pediatric SLE cases who had early disease onset (≤6 years) were enrolled in this study. All patients fulfilled the Systemic Lupus International Collaborating Clinics (SLICC) criteria. Genomic DNA was used for whole exome sequencing (WES). Pathogenic variants were confirmed by Sanger sequencing. Results: The median age at diagnosis of 15 early-onset SLE patients included in the study was 4 (2-6) years (F/M = 12/3). Significant gene mutations were detected in five of these patients (33.3%). Patients 1 and 2 with homozygous DNASE1L3 mutations [ c.320+4_320+7del and G188 A (c.563 G>C) variants] had skin involvement and oral ulcers. One of them (patient 1) had arthritis and nephritis, and another (patient 2) had nonscarring alopecia and thrombocytopenia. They are currently clinically inactive but have positive serological findings. Patient 3 with homozygous pathogenic ACP5 mutation [ G109 R (c.325 G>A) variant] had arthritis, nephritis, short stature, and skeletal dysplasia. Patient 4 with a heterozygote novel IFIH1 mutation [ L809 F (c.2425 C>T) variant] had skin findings and leukopenia. Patient 5 with novel C1S variant [homozygous C147 W (c.441 C>G) variant] had marked skin findings, oral ulcers, nonscarring alopecia, pancytopenia, and low total hemolytic complement CH50 level. All patients have responded to the treatments and have low Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) scores, on therapy. Conclusion: Genetic causes should be investigated in early-onset SLE, for better management and genetic counseling. On the other hand, multicenter studies may help to further define genotype-phenotype associations. [ABSTRACT FROM AUTHOR]

The subset of ovarian cancer (OC) diagnosed ≤ 30yo represents a distinct subgroup exhibiting disparities from late-onset OC in many aspects, including indefinite germline cancer predisposition. We performed DNA/RNA-WES with HLA-typing, PRS assessment and survival analysis in 123 early-onset OC-patients compared to histology/stage-matched late-onset and unselected OC-patients, and population-matched controls. Only 6/123(4.9%) early-onset OC-patients carried a germline pathogenic variant (GPV) in high-penetrance OC-predisposition genes. Nevertheless, our comprehensive germline analysis of early-onset OC-patients revealed two divergent trajectories of potential germline susceptibility. Firstly, overrepresentation analysis highlighted a connection to breast cancer (BC) that was supported by the CHEK2 GPV enrichment in early-onset OC(p = 1.2 × 10–4), and the presumably BC-specific PRS313, which successfully stratified early-onset OC-patients from controls(p = 0.03). The second avenue pointed towards the impaired immune response, indicated by LY75-CD302 GPV(p = 8.3 × 10–4) and diminished HLA diversity compared with controls(p = 3 × 10–7). Furthermore, we found a significantly higher overall GPV burden in early-onset OC-patients compared to controls(p = 3.8 × 10–4). The genetic predisposition to early-onset OC appears to be a heterogeneous and complex process that goes beyond the traditional Mendelian monogenic understanding of hereditary cancer predisposition, with a significant role of the immune system. We speculate that rather a cumulative overall GPV burden than specific GPV may potentially increase OC risk, concomitantly with reduced HLA diversity. [ABSTRACT FROM AUTHOR]

Young people often rely on family carers to access support for their mental health. However, stigma can be a barrier to help seeking for young people and families. Little research has been undertaken with young people who experience highly stigmatised symptoms, such as psychosis spectrum symptoms, and even less research has been conducted with parents and carers, meaning barriers to help go unchallenged. Therefore, this narrative review aimed to explore stories of family experiences of seeking help for young people with symptoms associated with the psychosis spectrum. Sources searched were PsycINFO and PubMed. Reference lists of the selected papers were also cross-checked to ensure the search had not missed potential papers for inclusion. Searches returned 139 results, of which 12 were identified for inclusion. A narrative analytic approach was adopted to synthesise qualitative findings to provide a nuanced interpretation of help-seeking experiences. The narrative synthesis provided an opportunity to identify differences, similarities, and patterns across the studies to tell a cumulative emancipatory narrative of family experiences of seeking help for psychosis spectrum symptoms. Help-seeking experiences had a relational impact on families, with stress adding to conflict and anxieties inhibiting hopefulness, although families could emerge stronger and assertively with compassionate support. [ABSTRACT FROM AUTHOR]

Small-Fiber Neuropathy (SFN) is a disorder of the peripheral nervous system, characterised by neuropathic pain; approximately 11% of cases are linked to variants in Voltage-Gated Sodium Channels (VGSCs). This study aims to broaden the genetic knowledge on painful SFN by applying Whole-Exome Sequencing (WES) in Early-Onset (EO) cases. A total of 88 patients from Italy (n = 52) and the Netherlands (n = 36), with a disease onset at age ≤ 45 years old and a Pain Numerical Rating Score ≥ 4, were recruited. After variant filtering and classification, WES analysis identified 142 potentially causative variants in 93 genes; 8 are Pathogenic, 15 are Likely Pathogenic, and 119 are Variants of Uncertain Significance. Notably, an enrichment of variants in transient receptor potential genes was observed, suggesting their role in pain modulation alongside VGSCs. A pathway analysis performed by comparing EO cases with 40 Italian healthy controls found enriched mutated genes in the "Nicotinic acetylcholine receptor signaling pathway". Targeting this pathway with non-opioid drugs could offer novel therapeutic avenues for painful SFN. Additionally, with this study we demonstrated that employing a gene panel of reported mutated genes could serve as an initial screening tool for SFN in genetic studies, enhancing clinical diagnostics. [ABSTRACT FROM AUTHOR]

Hope is an important but overlooked phenomenon in dementia studies. Few studies have examined how people with dementia experience or perceive hope, possibly because it is seen as a diagnosis without hope. In this article, we report on a doctoral study, the aim of which was to examine the phenomenon of hope from the perspective of younger people with dementia to generate new understanding and enable community-based healthcare professionals to support well-being. The study was conducted in the Midlands, England, and used a modified diary-interview method. Six participants were given a camera and asked to take pictures of whatever made them feel hopeful. During a post-diary semi-structured interview, a conversation about hope took place. Interviews were transcribed and interpreted using the 'Voice-Centred Relational Method'. Findings show that hope is important to younger people with dementia. Sources of hope were the surrounding environment, keeping connected, taking action, and drawing on internal resources. An over-arching theme was 'defying dementia' and participants demonstrated resistance to negative stereotypes. Living with dementia did not curtail hope, although it could be weakened when participants felt 'cast adrift' by services. The In vivo codes generated were fear of dementia, threats to identity, disconnection from others, and frustrations and restrictions. It is concluded that hope should be a more central part of practice-based conversations with people with dementia. [ABSTRACT FROM AUTHOR]

Abstract The subset of ovarian cancer (OC) diagnosed ≤ 30yo represents a distinct subgroup exhibiting disparities from late-onset OC in many aspects, including indefinite germline cancer predisposition. We performed DNA/RNA-WES with HLA-typing, PRS assessment and survival analysis in 123 early-onset OC-patients compared to histology/stage-matched late-onset and unselected OC-patients, and population-matched controls. Only 6/123(4.9%) early-onset OC-patients carried a germline pathogenic variant (GPV) in high-penetrance OC-predisposition genes. Nevertheless, our comprehensive germline analysis of early-onset OC-patients revealed two divergent trajectories of potential germline susceptibility. Firstly, overrepresentation analysis highlighted a connection to breast cancer (BC) that was supported by the CHEK2 GPV enrichment in early-onset OC(p = 1.2 × 10–4), and the presumably BC-specific PRS313, which successfully stratified early-onset OC-patients from controls(p = 0.03). The second avenue pointed towards the impaired immune response, indicated by LY75-CD302 GPV(p = 8.3 × 10–4) and diminished HLA diversity compared with controls(p = 3 × 10–7). Furthermore, we found a significantly higher overall GPV burden in early-onset OC-patients compared to controls(p = 3.8 × 10–4). The genetic predisposition to early-onset OC appears to be a heterogeneous and complex process that goes beyond the traditional Mendelian monogenic understanding of hereditary cancer predisposition, with a significant role of the immune system. We speculate that rather a cumulative overall GPV burden than specific GPV may potentially increase OC risk, concomitantly with reduced HLA diversity.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by a wide range of clinical manifestations and a relapsing-remitting course. The peak incidence of SLE occurs during the reproductive years; however, it can develop at any age. Late-onset SLE, which is diagnosed at age 50 or older, accounts for approximately 20% of all SLE cases. The comparison between late-onset SLE patients and their early-onset counterparts has revealed distinct differences in clinical characteristics, comorbidities, and mortality rates. Late-onset SLE patients exhibit lower frequencies of mucocutaneous, renal, hematological, and neuropsychiatric symptoms but higher rates of serositis, peripheral polyneuropathy, cardiovascular diseases, and pulmonary involvement. Additionally, they experience a greater burden of comorbidities and increased mortality rates. Here, we review the clinical characteristics, comorbidities, and mortality of patients with late-onset SLE.

Purpose: Early-onset breast cancer incidence has been increasing globally and in Taiwan. However, previous studies have not comprehensively examined how clinical and lifestyle characteristics influence the 5-year survival of breast cancer diagnosed at different stages of adulthood. Methods: We analyzed the Taiwan National Cancer Registry and Cause of Death datasets to understand how clinical factors (including tumor and treatment characteristics) and lifestyle factors (including body mass index, cigarette smoking, and alcohol consumption) were associated with the 5-year survival of 8471 young, 57,695 middle-aged, and 14,074 elderly female adult invasive breast cancer patients respectively diagnosed at age 20–39, 40–64, and ≥ 65 years between 2002 and 2015, with mortality follow-up to 2020. Poisson regression was used for obtaining the crude and adjusted 5-year survival risk ratios. Results: Clinical and lifestyle characteristics were distributed differently but had mostly similar direction of association with 5-year survival for the three age groups. Receiving any treatment was associated with better survival, especially for elderly patients. Being underweight at initial cancer treatment was associated with worse survival than having normal weight, especially for elderly patients. Current smokers had worse survival than never smokers for middle-aged and elderly patients. The 5-year breast cancer-specific survival was not significantly higher for those of age 45–49 years than 40–44 years, despite the recommended starting screening age is 45 years in Taiwan. Conclusion: Our findings contribute to the understanding of early-onset and later-onset female breast cancer characteristics and prognosis, which may inform surveillance and treatment strategies to achieve better breast cancer prognosis. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusions Merkel cell carcinoma (MCC) is a rare and highly aggressive form of skin cancer. However, there is limited research on the clinicopathological features of early‐onset MCC (EOMCC) and the differences between EOMCC and late‐onset MCC (LOMCC). Our objective was to evaluate the clinicopathological features and cancer‐specific survival (CSS) of EOMCC.Our cohort study analyzed data from the Surveillance, Epidemiology, and End Results (SEER) database from January 1, 2018, to December 31, 2020. Data from 1941 patients who were diagnosed with primary cutaneous MCC were included. We then divided the patients with MCC into two groups: those with EOMCC (526 patients) and those with LOMCC (1415 patients). CSS is used as the primary outcome.The EOMCC group exhibited trends toward advanced tumor progression, an expanded surgical scope, increased lymph node retrieval, intensified radiotherapy, greater utilization of systemic therapy, and a better prognosis. Multivariate analysis revealed that LOMCC (HR 3.305 [2.002–5.456], P < 0.001), advanced T stage (HR 1.430 [1.139–1.797], P = 0.002), advanced N stage (HR 1.522 [1.221–1.897], P < 0.001), M1 stage (HR 2.587 [1.480–4.521], P < 0.001), and radiation (HR 0.586 [0.410–0.837], P = 0.003) were significantly associated with CSS. Among these factors, EOMCC/LOMCC was most strongly associated with CSS, indicating that LOMCC is an independent risk factor for CSS. Interestingly, we found that regional EOMCC and localized or in situ LOMCC had almost completely overlapping survival curves (Plog‐rank = 0.620). Additionally, we observed that the TNM staging + age model was a more accurate predictor of CSS among MCC patients than using TNM staging alone.We found that EOMCC has distinct clinicopathological features compared to LOMCC. EOMCC is associated with better CSS. The combination of TNM staging and age was more accurate for predicting patient outcomes than TNM staging alone. [ABSTRACT FROM AUTHOR]

Objective: To study the clinical effect of group cognitive behavioral therapy to one-on-one treatment on patients with early-onset schizophrenia. Methods: Totally, 133 patients with early-onset schizophrenia admitted to the Department of Psychiatry of our hospital from September 2020 to September 2023 were selected and divided into a control group and an observation group according to whether group behavioral cognitive therapy was performed. The general demographic data of the patients were collected, and the propensity score matching method was used to balance the baseline data of the 2 groups. The Positive and negative syndrome scale, Personal and Social Performance Scale, severity of illness (SI), and efficacy index (EI) were compared between the 2 groups after matching. Results: After matching, 72 patients were included in our study. Compared to the control group, observation group PANSS score were decreased including after intervention (P > .05). Both groups showed a decrease between before and after treatments. Positive and Negative Syndrome Scale reduction rate after treatment and total response rate were increased in the observation group (P <.001). Personal and Social Performance Scale of the Clinical Global Impression (CGI) scores were higher than those of the control group. In the CGI scores, there is a significant difference that SI scores were lower in the observation group (P = .002), while EI scores were higher (P <.001). Conclusion: Group cognitive behavioral therapy is beneficial to the improvement of mental symptoms and disease severity, social function, and curative effect, which is advocated and popularized. [ABSTRACT FROM AUTHOR]

Background and Aim: The prognosis of early‐onset adenocarcinoma of esophagogastric junction (AEG) remains unclear. This research aimed at comparing the prognosis between early‐onset and late‐onset AEGs. Methods: We extracted eligible patients with surgically resected, pathologically confirmed, nonmetastatic AEG from the Surveillance, Epidemiology, and End Results database from 2004 to 2015. The cutoff age of early‐onset AEG was set at ≤50 years old. Univariate and multivariate Cox analysis as well as competing risk model were adopted for comparing overall survival (OS) and cancer‐specific survival (CSS) between early‐onset and late‐onset AEGs. In addition, multiple imputation and propensity score matching (PSM) were also carried out for sensitivity analysis. Results: In total, 4610 eligible AEG patients were collected in this study, including 610 early‐onset AEGs and 4000 late‐onset AEGs. Kaplan–Meier curves revealed significantly better survival in early‐onset AEGs than late‐onset AEGs. After interpolating missing data by multiple imputation, multivariate Cox regression analysis similarly showed better OS and CSS in early‐onset AEGs. By using PSM analysis at a ratio of 1:1, we matched 610 early‐onset AEG patients with 610 late‐onset AEG patients. After PSM, univariate Cox regression model still revealed favorable prognosis in early‐onset AEGs. Similar results were confirmed by performing PSM analysis at a ratio of 1:2 and 1:3. In addition, competing risk model demonstrated significantly lower cancer‐specific death in early‐onset AEGs compared to late‐onset AEGs before and after matching. Conclusion: By applying several effective sensitivity analyses, we reported significantly favorable OS and CSS in early‐onset AEGs compared to late‐onset AEGs. [ABSTRACT FROM AUTHOR]

Psychiatric illnesses can affect the social transitions of adolescence and young adulthood, such as completing education and entering working life and relationships. However, associations between earlier onset age and long-term outcomes among those with early-onset psychoses (EOP) are unclear, as are the long-term outcomes of EOP compared to non-psychotic disorders. We used national register data of the Northern Finland Birth Cohort 1986 to detect persons with EOP and other early-onset psychiatric disorders. The long-term clinical and work-family outcomes of persons with onset age before 18 years (n = 41 psychoses, n = 495 non-psychoses) or between 18–22 years (n = 61 psychoses, n = 377 non-psychoses) were compared. Individuals with the onset of psychosis between 18–22 years had significantly more unfavourable long-term outcomes when compared to those with psychosis onset before 18 years. Persons with psychosis onset before the age of 18 years had similar outcomes to those with non-psychotic psychiatric disorder onset before 18 years regarding educational level, marital status, having children, and substance use disorders. Individuals with EOP were more often on a disability pension compared to those with other early-onset mental disorders. Adjusting for sex, educational level and substance use only slightly diluted these results. Unexpectedly, later onset age of EOP was associated with worse outcomes. Those with psychosis onset between 18–22 years of age are in a critical period, which underlines the importance of investing on interventions in this age group. Further studies on the effect of the onset age on later outcomes in EOP are needed. [ABSTRACT FROM AUTHOR]

Early-onset mental disorders are associated with disrupted neurodevelopmental processes during adolescence. The methylazoxymethanol acetate (MAM) animal model, in which disruption in neurodevelopmental processes is induced, mimics the abnormal neurodevelopment associated with early-onset mental disorders from an etiological perspective. We conducted longitudinal structural magnetic resonance imaging (MRI) scans during childhood, adolescence, and adulthood in MAM rats to identify specific brain regions and critical windows for intervention. Then, the effect of repetitive transcranial magnetic stimulation (rTMS) intervention on the target brain region during the critical window was investigated. In addition, the efficacy of this intervention paradigm was tested in a group of adolescent patients with early-onset mental disorders (diagnosed with major depressive disorder or bipolar disorder) to evaluate its clinical translational potential. The results demonstrated that, compared to the control group, the MAM rats exhibited significantly lower striatal volume from childhood to adulthood (all P <0.001). In contrast, the volume of the hippocampus did not show significant differences during childhood (P >0.05) but was significantly lower than the control group from adolescence to adulthood (both P <0.001). Subsequently, rTMS was applied to the occipital cortex, which is anatomically connected to the hippocampus, in the MAM models during adolescence. The MAM-rTMS group showed a significant increase in hippocampal volume compared to the MAM-sham group (P <0.01), while the volume of the striatum remained unchanged (P >0.05). In the clinical trial, adolescents with early-onset mental disorders showed a significant increase in hippocampal volume after rTMS treatment compared to baseline (P <0.01), and these volumetric changes were associated with improvement in depressive symptoms (r = − 0.524, P = 0.018). These findings highlight the potential of targeting aberrant hippocampal development during adolescence as a viable intervention for early-onset mental disorders with neurodevelopmental etiology as well as the promise of rTMS as a therapeutic approach for mitigating aberrant neurodevelopmental processes and alleviating clinical symptoms. [ABSTRACT FROM AUTHOR]

Aim: To evaluate temporal changes in metastatic colorectal cancer (mCRC), incidence, and use of chemotherapy treatment by age group using real-world data (RWD) from the USA. Methods: A retrospective, observational study describing temporal trends in mCRC incidence and FOLFOXIRI treatment by age group using a nationwide database of commercially and Medicare Advantage-insured patients from 2010 to 2019. Results: Incidence of mCRC increased by 22.1 and 14.9% in the 18–49 and 50–64 years cohorts, respectively, and decreased by 21.6% in the ≥65 years cohort. Overall, younger patients were more likely to receive FOLFOXIRI treatment versus older patients. Conclusion: The shifting age distribution of mCRC should be considered when recommending screening and treatment. Further research is needed to inform age-specific treatment guidelines. Plain language summary What is this article about? This article reports the results of a study that used a US database of commercially and Medicare Advantage-insured adults to evaluate how the number of adults with metastatic colorectal cancer (mCRC) in three age groups (18–49 years, 50–64 years and 65 years and over) changed from 2010 to 2019. The study also looked at the use of an aggressive chemotherapy treatment, known as 5-fluorouracil, oxaliplatin, leucovorin calcium and irinotecan (FOLFOXIRI), by age group. What were the results? Overall, 23,970 adults with mCRC were included in the study. From 2010 to 2019, the number of adults with mCRC increased by 22.1% among those aged 18–49 years, increased by 14.9% among those aged 50–64 years, and decreased by 21.6% among those aged 65 years and over. There were some differences between age groups; a higher percentage of younger patients (18–49 years) were Hispanic or Asian, and from the South compared with the older age groups. In comparison, those aged 65 years and over were more likely to be from the West and Northeast of the USA. The study also found that a higher proportion of those aged 18–49 years received FOLFOXIRI (8.4%) compared with adults aged 50–64 years (4.4%) and 65 years and over (1.9%). What do the results of the study mean? Healthcare providers should be aware that early-onset mCRC is becoming more common and consider this when recommending screening and treatment. Summary points A rise in early-onset metastatic colorectal cancer (mCRC) has been observed in high-income countries, in contrast with the steady decline in late-onset mCRC due to improved screening. Contemporary data are required to better understand temporal changes in mCRC incidence by age group in the USA. This retrospective, observational cohort study used a database of commercially and Medicare Advantage-insured patients enrolled between 2010 and 2019 to describe temporal trends in mCRC incidence, patient characteristics, and treatment regimens by age group. Among patients aged 18–49 years, the standardized incidence rate (IR) for mCRC increased by 22.1% in 2010 to 2019, with an annual percentage change (APC) of 2.8%; in the 50–64 years cohort, the standardized IR increased by 14.9%, with an APC of 2.3%; in the ≥65 years cohort, the standardized IR decreased by 21.6%, with an APC of −2.1%. Patient characteristics varied between age groups, with a higher proportion of patients with early-onset mCRC being Hispanic or Asian, from the Southern USA and having commercial rather than Medicare Advantage insurance compared with patients with late-onset mCRC. Exploratory analyses suggested that a higher proportion of patients with early-onset mCRC received more aggressive multiagent chemotherapy compared with patients with late-onset mCRC. These findings add to the accumulating evidence of a rise in the incidence of early-onset mCRC and increasing use of aggressive chemotherapy regimens in these patients without a confirmed corresponding survival benefit. The shifting age distribution and patient characteristics in mCRC should be considered when developing appropriate treatment guidelines. [ABSTRACT FROM AUTHOR]

Early-onset colorectal cancer emerges as a distinctive clinical and biological entity and is generally defined as the onset of colon or rectal neoplasia before the age of 50. Several reports describe an increasing incidence worldwide of colorectal cancers occurring in individuals younger than 50 years, along with particular histologic and molecular features. Although heredity may be an explanation in some cases with young-onset colorectal cancer, other driving factors remain partially unknown. The present study explores demographic, clinical, and pathological features within a group of patients diagnosed with colorectal cancer before the age of 50. It is a retrospective survey based on data collected between 2017 and 2023 within three surgical departments from a tertiary Romanian hospital. The clinical and pathological features we identified (later-stage disease, distal colon tumor localization, mucinous histology) are mainly superimposed with the existing data in the literature regarding this pathology. In order to lower the burden that colorectal neoplasia diagnosed in the young implies, a change of paradigm should be made in terms of establishing effective and targeted screening programs but also in the direction of enhancing complex clinical, pathological, and molecular diagnosis. [ABSTRACT FROM AUTHOR]

Background: Early-onset colorectal cancer (CRC), defined as diagnosis before age 50, has increased in recent decades. Although more often diagnosed at advanced stage, associations with other histological and molecular markers that impact prognosis and treatment remain to be clarified. We conducted a systematic review and meta-analysis concerning the prevalence of prognostic and predictive tumor markers for early- vs. late-onset CRC, including oncogene mutations, microsatellite instability (MSI), and emerging markers including immune cells and the consensus molecular subtypes. Methods: We systematically searched PubMed for original research articles published between April 2013-January 2024. Included studies compared the prevalence of tumor markers in early- vs. late-onset CRC. A meta-analysis was completed and summary odds ratios (ORs) with 95% confidence intervals (CIs) were obtained from a random effects model via inverse variance weighting. A sensitivity analysis was completed to restrict the meta-analysis to studies that excluded individuals with Lynch syndrome, a hereditary condition that influences the distribution of tumor markers for early-onset CRC. Results: In total, 149 articles were identified. Tumors from early-onset CRC are less likely to include mutations in KRAS (OR, 95% CI: 0.91, 0.85-0.98), BRAF (0.63, 0.51-0.78), APC (0.70, 0.58-0.84), and NRAS (0.88, 0.78-1.00) but more likely to include mutations in PTEN (1.68, 1.04-2.73) and TP53 (1.34, 1.24-1.45). After limiting to studies that excluded Lynch syndrome, the associations between early-onset CRC and BRAF (0.77, 0.64-0.92) and APC mutation (0.81, 0.67-0.97) were attenuated, while an inverse association with PIK3CA mutation was also observed (0.88, 0.78-0.99). Early-onset tumors are less likely to develop along the CpG Island Methylator Phenotype pathway (0.24, 0.10-0.57), but more likely to possess adverse histological features including high tumor grade (1.20, 1.15-1.25), and mucinous (1.22, 1.16-1.27) or signet ring histology (2.32, 2.08-2.57). A positive association with MSI status (1.31, 1.11-1.56) was also identified. Associations with immune markers and the consensus molecular subtypes are inconsistent. Discussion: A lower prevalence of mutations in KRAS and BRAF is consistent with extended survival and superior response to targeted therapies for metastatic disease. Conversely, early-onset CRC is associated with aggressive histological subtypes and TP53 and PTEN mutations, which may serve as therapeutic targets. [ABSTRACT FROM AUTHOR]

Early-onset breast cancer (EoBC), defined by a diagnosis <40 years of age, is associated with poor prognosis. This study investigated the mutational landscape of non-metastatic EoBC and the prognostic relevance of mutational signatures using 100 tumour samples from Alberta, Canada. The MutationalPatterns package in R/Bioconductor was used to extract de novo single-base substitution (SBS) and insertion–deletion (indel) mutational signatures and to fit COSMIC SBS and indel signatures. We assessed associations between these signatures and clinical characteristics of disease, in addition to recurrence-free (RFS) and overall survival (OS). Five SBS and two indel signatures were extracted. The SBS13-like signature had higher relative contributions in the HER2-enriched subtype. Patients with higher than median contribution tended to have better RFS after adjustment for other prognostic factors (HR = 0.29; 95% CI: 0.08–1.06). An unsupervised clustering algorithm based on absolute contribution revealed three clusters of fitted COSMIC SBS signatures, but cluster membership was not associated with clinical variables or survival outcomes. The results of this exploratory study reveal various SBS and indel signatures may be associated with clinical features of disease and prognosis. Future studies with larger samples are required to better understand the mechanistic underpinnings of disease progression and treatment response in EoBC. [ABSTRACT FROM AUTHOR]

Background: The incidence of colorectal cancer (CRC) has been steadily increasing in younger individuals over the past several decades for reasons that are incompletely defined. Identifying differences in gene expression profiles, or transcriptomes, in early-onset colorectal cancer (EOCRC, < 50 years old) patients versus later-onset colorectal cancer (LOCRC, > 50 years old) patients is one approach to understanding molecular and genetic features that distinguish EOCRC. Methods: We performed RNA-sequencing (RNA-seq) to characterize the transcriptomes of patient-matched tumors and adjacent, uninvolved (normal) colonic segments from EOCRC (n=21) and LOCRC (n=22) patients. The EOCRC and LOCRC cohorts were matched for demographic and clinical characteristics. We used The Cancer Genome Atlas Colon Adenocarcinoma (TCGA-COAD) database for validation. We used a series of computational and bioinformatic tools to identify EOCRC-specific differentially expressed genes, molecular pathways, predicted cell populations, differential gene splicing events, and predicted neoantigens. Results: We identified an eight-gene signature in EOCRC comprised of ALDOB, FBXL16, IL1RN, MSLN, RAC3, SLC38A11, WBSCR27 and WNT11, from which we developed a score predictive of overall CRC patient survival. On the entire set of genes identified in normal tissues and tumors, cell type deconvolution analysis predicted a differential abundance of immune and non-immune populations in EOCRC versus LOCRC. Gene set enrichment analysis identified increased expression of splicing machinery in EOCRC. We further found differences in alternative splicing (AS) events, including one within the long non-coding RNA, HOTAIRM1. Additional analysis of AS found seven events specific to EOCRC that encode potential neoantigens. Conclusion: Our transcriptome analyses identified genetic and molecular features specific to EOCRC which may inform future screening, development of prognostic indicators, and novel drug targets. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to identify prognostic factors and develop a nomogram for predicting overall survival (OS) in stage III/IV early-onset colorectal cancer (EO-CRC). Methods: Stage III/IV EO-CRC patients were identified from the Surveillance, Epidemiology, and End Results (SEER) database between 2010 and 2015. The datasets were randomly divided (2:1) into training and validation sets. A nomogram predicting OS was developed based on the prognostic factors identified by Cox regression analysis in the training cohort. Moreover, the predictive performance of the nomogram was assessed using the receiver operating characteristic (ROC) curves, calibration plots, and decision curve analysis (DCA). Subsequently, the internal validation was performed using the validation cohort. Finally, a risk stratification system was established based on the constructed nomogram. Results: Of the 10,387 patients diagnosed with stage III/IV EO-CRC between 2010 and 2015 in the SEER database, 8,130 patients were included. In the training cohort (n=3,071), sex, marital status, race/ethnicity, primary site, histologic subtypes, grade, T stage, and N stage were identified as independent prognostic variables for OS. The 1-, 3-, and 5-year area under the curve (AUC) values of the nomogram were robust in both the training (0.751, 0.739, and 0.723) and validation cohorts (0.748, 0.733, and 0.720). ROC, calibration plots, and DCA indicated good predictive performance of the nomogram in both the training and validation sets. Furthermore, patients were categorized into low-, middle-, and high-risk groups based on the nomogram risk score. Kaplan-Meier curve showed significant survival differences between the three groups. Conclusion: We developed a prognostic nomogram and risk stratification system for stage III/IV EO-CRC, which may facilitate clinical decision-making and individual prognosis prediction. [ABSTRACT FROM AUTHOR]

BackgroundThe global status of chronic kidney disease (CKD) is underestimated, particularly the burden on adolescents and young adults (early-onset, aged 15–39).ObjectiveWe aim to investigate the pattern and trend of early-onset CKD from 1990 to 2019.MethodsWe analyzed age-specific rates of early-onset CKD incidence, death, and disability-adjusted life years (DALY) using Global Burden of Disease Study 2019 data. We examined the global, regional, national, gender-based, age group-based, and temporal changes of early-onset CKD burden from 1990 to 2019, as well as proportional DALY attributions of various risk factors.ResultsFrom 1990 to 2019, the global age-specific incidence rate (per 100,000 population) significantly increased from 25.04 (95% confidence interval 18.51, 31.65) to 32.21 (23.73, 40.81) for early-onset CKD. However, the global age-specific death rate significantly decreased from 2.96 (2.76, 3.15) to 2.86 (2.61, 3.11), and the age-specific DALY rate remained stable. Regarding sociodemographic indexes (SDI), countries with middle SDI had the highest incidence rates and the fastest increasing trends, while those with low and low-middle SDI experienced the highest death and DALY rates. Women had a generally higher age-specific incidence rate than men, whereas men showed higher age-specific death and DALY rates. In addition, the burdens of CKD increased with age among adolescents and young adults. Moreover, the main attributable risk factors for DALY of early-onset CKD were high systolic blood pressure (SBP), fasting plasma glucose (FPG), and body mass index (BMI).ConclusionThe age-specific incidence rate of early-onset CKD increased significantly from 1990 to 2019, and the age-specific DALY rate remained stable. High SBP, high FPG, and high BMI were the primary risk factors. Targeted prevention and healthcare measures should be developed considering age, gender, and region.

ObjectiveWe summarize the global, regional, and national burden of inflammatory bowel disease (IBD) in children and adolescents from 1990 to 2019.MethodsBased on the Global Burden of Disease Study 2019, the data of IBD in children and adolescents were analyzed by sex, age, year, and location. Joinpoint analysis was applied to assess the temporal trend of the disease burden.ResultsFrom 1990 to 2019, the incidence of IBD in children and adolescents increased by 22.8%, from 20,897.42 to 25,658.55 cases, especially in high SDI region. During the same period, the DALY numbers decreased by 53.5%, from 243,081.06 to 113,119.86, with all SDI regions experiencing a clear drop in DALYs except high SDI regions. In 2019, early-onset IBD incidence and DALY numbers were reported at 2,053.52 (95% UI: 1,575.62 to 2,677.49) and 73,797.46 (95% UI: 43,655.86 to 105,998.63), respectively.ConclusionEarly-onset IBD in children and adolescents remains a significant global health concern. The disease burden has not improved in developed countries over the past 30 years, highlighting the need for targeted interventions.

BackgroundIntrahepatic cholestasis of pregnancy (ICP) and gestational diabetes mellitus (GDM) are two common pregnancy complications that pose considerable health challenges. The interplay between these conditions is believed to significantly influence pregnancy outcomes, yet the nature of this relationship remains elusive. This study was designed to elucidate the connection between ICP and GDM.MethodsThis retrospective cohort study included 742 singleton pregnancies delivered at the Shanghai Public Health Clinical Center from January 2015 to December 2023. We compared the incidence of GDM and pregnancy outcomes between multiple ICP subgroups and a control group of healthy pregnancies. A multivariate regression model was used to measure the independent association between ICP and propensity for GDM development, as well as to assess the impact of potential bidirectional effects between ICP and GDM.ResultsThe results indicate that the incidence of GDM is highest in the early-onset ICP (diagnosed before the 24th week of gestation) group compared to the control group and other ICP subgroups. Early-onset ICP is an independent risk factor for the development of GDM, with other risk factors including age, history of abortion, family history of diabetes, and elevated ALT levels. Subgroup interaction analysis did not reveal heterogeneity in the influence of early-onset ICP on the development of GDM across different subgroups. Further analysis showed that GDM itself does not increase the risk of late-onset ICP. Additionally, when comparing pregnancy outcomes between GDM patients with or without ICP, those with both GDM and ICP had significantly higher rates of preterm birth, cesarean section, and small for gestational age (SGA) compared to patients with GDM alone. Furthermore, elevated TBA levels (first diagnosed) of early-onset ICP patients were associated with an increased risk of GDM in a nonlinear fashion.ConclusionOur study indicated that early-onset ICP is significantly linked to an increased risk of GDM. Further research is warranted to explore the mechanisms behind this association and to develop strategies for early identification and intervention to mitigate GDM risk.

Abstract Background Lipid metabolism changes occur in early Alzheimer's disease (AD) patients. Yet little is known about metabolic gene changes in early AD cortex. Methods The lipid metabolic genes selected from two datasets (GSE39420 and GSE118553) were analyzed with enrichment analysis. Protein–protein interaction network construction and correlation analyses were used to screen core genes. Literature analysis and molecular docking were applied to explore potential therapeutic drugs. Results 60 lipid metabolic genes differentially expressed in early AD patients’ cortex were screened. Bioinformatics analyses revealed that up-regulated genes were mainly focused on mitochondrial fatty acid oxidation and mediating the activation of long-chain fatty acids, phosphoproteins, and cholesterol metabolism. Down-regulated genes were mainly focused on lipid transport, carboxylic acid metabolic process, and neuron apoptotic process. Literature reviews and molecular docking results indicated that ACSL1, ACSBG2, ACAA2, FABP3, ALDH5A1, and FFAR4 were core targets for lipid metabolism disorder and had a high binding affinity with compounds including adenosine phosphate, oxidized Photinus luciferin, BMS-488043, and candidate therapeutic drugs especially bisphenol A, benzo(a)pyrene, ethinyl estradiol. Conclusions AD cortical lipid metabolism disorder was associated with the dysregulation of the PPAR signaling pathway, glycerophospholipid metabolism, adipocytokine signaling pathway, fatty acid biosynthesis, fatty acid degradation, ferroptosis, biosynthesis of unsaturated fatty acids, and fatty acid elongation. Candidate drugs including bisphenol A, benzo(a)pyrene, ethinyl estradiol, and active compounds including adenosine phosphate, oxidized Photinus luciferin, and BMS-488043 have potential therapeutic effects on cortical lipid metabolism disorder of early AD.

Early-onset (age < 65) Alzheimer's disease is associated with greater non-amnestic cognitive symptoms and neuropathological burden than late-onset disease. It is not fully understood whether these groups also differ in the associations between molecular pathology, neurodegeneration and cognitive performance. We studied amyloid-positive patients with early-onset (n = 60, mean age 58 ± 4, MMSE 21 ± 6, 58% female) and late-onset (n = 53, mean age 74 ± 6, MMSE 23 ± 5, 45% female) Alzheimer's disease who underwent neurological evaluation, neuropsychological testing, 11C-Pittsburgh compound B PET (amyloid-PET) and 18F-flortaucipir PET (tau-PET). 18F-fluorodeoxyglucose PET (brain glucose metabolism PET) was also available in 74% (n = 84) of participants. Composite scores for episodic memory, semantic memory, language, executive function and visuospatial domains were calculated based on cognitively unimpaired controls. Voxel-wise regressions evaluated correlations between PET biomarkers and cognitive scores and early-onset versus late-onset differences were tested with a PET × Age group interaction. Mediation analyses estimated direct and indirect (18F-fluorodeoxyglucose mediated) local associations between 18F-flortaucipir binding and cognitive scores in domain-specific regions of interest. We found that early-onset patients had higher 18F-flortaucipir binding in parietal, lateral temporal and lateral frontal cortex; more severe 18F-fluorodeoxyglucose hypometabolism in the precuneus and angular gyrus; and greater 11C-Pittsburgh compound B binding in occipital regions compared to late-onset patients. In our primary analyses, PET-cognition correlations did not meaningfully differ between age groups.18F-flortaucipir and 18F-fluorodeoxyglucose, but not 11C-Pittsburgh compound B, were significantly associated with cognition in expected domain-specific patterns in both age groups (e.g. left perisylvian/language, frontal/executive, occipital/visuospatial). 18F-fluorodeoxyglucose mediated the relationship between 18F-flortaucipir and cognition in both age groups across all domains except episodic memory in late-onset patients. Additional direct effects of 18F-flortaucipir were observed for executive function in all age groups, language in early-onset Alzheimer's disease and in the total sample and visuospatial function in the total sample. In conclusion, tau and neurodegeneration, but not amyloid, were similarly associated with cognition in both early and late-onset Alzheimer's disease. Tau had an association with cognition independent of neurodegeneration in language, executive and visuospatial functions in the total sample. Our findings support tau PET as a biomarker that captures both the clinical severity and molecular pathology specific to Alzheimer's disease across the broad spectrum of ages and clinical phenotypes in Alzheimer's disease.

BackgroundGenetics and biology may influence the age of onset of anorexia nervosa (AN). The aims of this study were to determine whether common genetic variation contributes to age of onset of AN and to investigate the genetic associations between age of onset of AN and age at menarche.MethodsA secondary analysis of the Psychiatric Genomics Consortium genome-wide association study (GWAS) of AN was performed, which included 9335 cases and 31,981 screened controls, all from European ancestries. We conducted GWASs of age of onset, early-onset AN (

Background: Microsatellite instability (MSI) is an important prognosticator for colorectal cancer (CRC). The present study aimed to assess the impact of MSI status on the characteristics and outcomes of early-onset compared to late-onset rectal cancer. Methods: This retrospective cohort study used data from the US National Cancer Database (2004–2019) to assess the baseline characteristics, treatment patterns, short-term outcomes, and overall survival (OS) of early-onset rectal adenocarcinoma affecting patients < 50 years compared to late-onset rectal adenocarcinoma according to the MSI status. Results: The present study included 48,407 patients (59.9% male) with rectal cancer, 17.3% of patients were < 50 years and 6.3% had MSI-H tumors. In the early-onset group, patients with MSI-H tumors had a lower mean age (41.5 vs 43 years, p < 0.001) and presented less often with stage IV disease (22.1% vs 17.7%, p = 0.03) and liver metastasis (9.1% vs 13.5%, p = 0.011) than patients with MSS tumors. In the late-onset group, patients with MSI-H and MSS tumors had similar demographics, disease stage, and metastatic pattern, yet MSI-H patients more often received neoadjuvant radiation therapy (58.9% vs 55.1%, p = 0.009) and neoadjuvant systemic therapy (40% vs 36.2%, p = 0.005). In both age groups, MSI-H tumors were associated with more pathologic T3-4 stage and were more likely mucinous and poorly differentiated carcinomas than MSS tumors. The median OS of MSI-H tumors was similar to MSS tumors (108.09 vs 102.31 months, p = 0.1), whether in the early-onset (139.5 vs 134.2 months, p = 0.821) or late-onset groups (106.1 vs 104.3 months, p = 0.236). Conclusions: In both age groups, MSI-H rectal cancers were more often mucinous and poorly differentiated carcinomas and had pT3-4 stage more often than MSS cancers. MSI-H rectal cancers tend to present less often with distant metastases and nodal involvement than MSS cancers only in early-onset, but not in late-onset rectal cancers. The association between MSI status and survival was not notable in this study, whether in the early-onset or late-onset groups. [ABSTRACT FROM AUTHOR]

Background: Lipid metabolism changes occur in early Alzheimer's disease (AD) patients. Yet little is known about metabolic gene changes in early AD cortex. Methods: The lipid metabolic genes selected from two datasets (GSE39420 and GSE118553) were analyzed with enrichment analysis. Protein–protein interaction network construction and correlation analyses were used to screen core genes. Literature analysis and molecular docking were applied to explore potential therapeutic drugs. Results: 60 lipid metabolic genes differentially expressed in early AD patients' cortex were screened. Bioinformatics analyses revealed that up-regulated genes were mainly focused on mitochondrial fatty acid oxidation and mediating the activation of long-chain fatty acids, phosphoproteins, and cholesterol metabolism. Down-regulated genes were mainly focused on lipid transport, carboxylic acid metabolic process, and neuron apoptotic process. Literature reviews and molecular docking results indicated that ACSL1, ACSBG2, ACAA2, FABP3, ALDH5A1, and FFAR4 were core targets for lipid metabolism disorder and had a high binding affinity with compounds including adenosine phosphate, oxidized Photinus luciferin, BMS-488043, and candidate therapeutic drugs especially bisphenol A, benzo(a)pyrene, ethinyl estradiol. Conclusions: AD cortical lipid metabolism disorder was associated with the dysregulation of the PPAR signaling pathway, glycerophospholipid metabolism, adipocytokine signaling pathway, fatty acid biosynthesis, fatty acid degradation, ferroptosis, biosynthesis of unsaturated fatty acids, and fatty acid elongation. Candidate drugs including bisphenol A, benzo(a)pyrene, ethinyl estradiol, and active compounds including adenosine phosphate, oxidized Photinus luciferin, and BMS-488043 have potential therapeutic effects on cortical lipid metabolism disorder of early AD. [ABSTRACT FROM AUTHOR]

Alzheimer’s disease (AD) is the most common type of cognitive impairment in the elderly. In this report, we presented a case of a 52-year-old woman with rapid disease progression within 6  months. She was diagnosed with mild dementia according to the clinical symptoms and neuropsychological assessment results. Based on the results of neuropathological proteins in cerebrospinal fluid, cranial magnetic resonance imaging, and positron emission tomography/computed tomography, the patient showed the presence of β amyloid deposition, pathologic tau along with neurodegeneration [A+T+(N+)], indicative of AD. Whole exome sequencing revealed a heterozygous C-to-T missense mutation of nucleotide 3,755 (c.3755C  >  T) in exon 25 of the angiotensin converting enzyme (ACE) gene on chromosome 17q23 (rs762056936). [ABSTRACT FROM AUTHOR]

Purpose: The study compares the surgical outcomes of very-early-onset ulcerative colitis (VEO-UC), which is a rare disease diagnosed in pediatric patients < 6 years, with those of older pediatric patients with ulcerative colitis (UC). Methods: A retrospective observational study of 57 pediatric patients with UC was conducted at a single center. The study compared surgical complications and postoperative growth between the two groups. Results: Out of the 57 patients, 6 had VEO-UC, and 5 of them underwent total colectomy. Compared with the surgical cases of older patients with UC (n = 6), the rate of postoperative complications in patients with VEO-UC (n = 5) was not significantly different, except for high-output ileostomy (80% vs. 0% at 3 weeks postoperatively, p = 0.02). The rate of postoperative central venous catheter (CVC) placement at > 90 days was higher in patients with VEO-UC (100% vs. 17%, p = 0.02). The median change in the Z-score of height before and 2 years after colectomy was not significantly different between VEO-UC and older patients (1.1 vs. 0.3, p = 0.13). Conclusion: With regard to complications and outcomes, total colectomy for VEO-UC patients and that for older pediatric UC patients is comparable. However, high-output ileostomy and the long duration of CVC placement may pose management challenges. [ABSTRACT FROM AUTHOR]

We aimed to compare the prevalence of modifiable and non-modifiable coronary heart disease (CHD) risk factors among those with premature CHD and healthy individuals. PubMed, CINAHL, Embase, and Web of Science databases were searched (review protocol is registered in PROSPERO CRD42020173216). The quality of studies was assessed using the National Heart, Lung and Blood Institute tool for cross-sectional, cohort and case-control studies. Meta-analyses were performed using Review Manager 5.3. Effect sizes for categorical and continuous variables, odds ratio (OR) and mean differences (MD)/standardised mean differences (SMD) with 95% confidence intervals (CI) were reported. A total of n=208 primary studies were included in this review. Individuals presenting with premature CHD (PCHD, age ≤65 years) had higher mean body mass index (MD 0.54 kg/m2, 95% CI 0.24, 0.83), total cholesterol (SMD 0.27, 95% CI 0.17, 0.38), triglycerides (SMD 0.50, 95% CI 0.41, 0.60) and lower high-density lipoprotein cholesterol (SMD 0.79, 95% CI: −0.91, −0.68) compared with healthy individuals. Individuals presenting with PCHD were more likely to be smokers (OR 2.88, 95% CI 2.51, 3.31), consumed excessive alcohol (OR 1.40, 95% CI 1.05, 1.86), had higher mean lipoprotein (a) levels (SMD 0.41, 95% CI 0.28, 0.54), and had a positive family history of CHD (OR 3.65, 95% CI 2.87, 4.66) compared with healthy individuals. Also, they were more likely to be obese (OR 1.59, 95% CI 1.32, 1.91), and to have had dyslipidaemia (OR 2.74, 95% CI 2.18, 3.45), hypertension (OR 2.80, 95% CI 2.28, 3.45), and type 2 diabetes mellitus (OR 2.93, 95% CI 2.50, 3.45) compared with healthy individuals. This meta-analysis confirms current knowledge of risk factors for PCHD, and identifying these early may reduce CHD in young adults. [ABSTRACT FROM AUTHOR]

Favipiravir terminates severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) replication. Accordingly, early administration of favipiravir to SARS-CoV-2-infected coronavirus disease 2019 (COVID-19) patients may be expected to suppress disease progression. A randomized double-blind placebo-controlled trial was conducted to demonstrate efficacy of favipiravir in reducing disease progression in patients with mild COVID-19. The participants were unvaccinated patients with comorbidities and at risk of progression to severe disease. Patients were enrolled within 72 h of disease onset and randomized to receive either favipiravir (1800 mg/dose on Day 1 followed by 800 mg/dose) or matching placebo twice daily for 10 days. The primary endpoint was the proportion of patients requiring oxygen therapy within 28 days of randomization. The trial was discontinued after enrolling 84 patients due to slower than anticipated enrollment caused by rapid uptake of SARS-CoV-2-vaccines and the emergence of the Omicron variant. Results from the 84 patients demonstrated no significant difference in all clinical outcomes. In post-hoc analyses, favipiravir treatment showed higher efficacy in patients within 48 h of onset. No deaths or severe adverse events were documented in the favipiravir group. Plasma concentrations of favipiravir from Day 2 onward were maintained above 40 μg/mL. Conducting clinical trials for pathogens like SARS-CoV-2 that rapidly accumulate mutations leading to altered disease characteristics carries significant risks unless it can be done in a short period. Therefore, it would be important to prepare the comprehensive clinical trial platform that can appropriately and promptly evaluate drugs even under a pandemic. [ABSTRACT FROM AUTHOR]

Background: Comorbidities reduce quality of life for people with dementia and caregivers. Some comorbidities share a genetic basis with dementia. Objective: The objective of this study is to assess comorbidity in patients with different dementia subtypes in order to better understand the pathogenesis of dementias. Methods: A total of 298 patients with dementia were included. We collected some common comorbidities. We analyzed the differences in comorbidities among patients with dementia according to clinical diagnosis, age of onset (early-onset: < 65 and late-onset: ≥65 years old) and apolipoprotein (APOE) genotypes by using the univariate and multivariate approaches. Results: Among 298 participants, there were 183 Alzheimer's disease (AD), 40 vascular dementia (VaD), 37 frontotemporal dementia (FTLD), 20 Lewy body dementia (LBD), and 18 other types of dementia. Based on age of onset, 156 cases had early-onset dementia and 142 cases had late-onset dementia. The most common comorbidities observed in all dementia patients were hyperlipidemia (68.1%), hypertension (39.9%), insomnia (21.1%), diabetes mellitus (19.5%), and hearing impairment (18.1%). The prevalence of hypertension and cerebrovascular disease was found to be higher in patients with VaD compared to those with AD (p = 0.002, p < 0.001, respectively) and FTLD (p = 0.028, p = 0.004, respectively). Additionally, patients with late-onset dementia had a higher burden of comorbidities compared to those with early-onset dementia. It was observed that APOE ɛ4/ɛ4 carriers were less likely to have insomnia (p = 0.031). Conclusions: Comorbidities are prevalent in patients with dementia, with hyperlipidemia, hypertension, insomnia, diabetes, and hearing impairment being the most commonly observed. Comorbidity differences existed among different dementia subtypes. [ABSTRACT FROM AUTHOR]

Prostate cancer is one of the two most common non‐cutaneous cancers in men. Its presentation might be with unusual symptoms and cause the wrong initial diagnosis. This case report discusses a rare neurologic manifestation of advanced metastatic cancer in a low‐risk man. He had been receiving treatment for multiple sclerosis incorrectly due to unusual manifestations such as claudication and pelvic, leg, and shoulder pain. The patient underwent a whole‐body bone scan and then a transrectal ultrasound‐guided biopsy, which confirmed metastatic prostate cancer with a Gleason score between 7/10 and 10/10 in all samples. Following treatment with chemotherapeutic injections (docetaxel), luteinizing hormone‐releasing hormone (LHRH) analogous (Zoladex), and testosterone‐suppressing tablets (abiraterone), the disease has been under control and prostate‐specific antigen (PSA) level has decreased significantly. The most common sites of metastasis are regional lymph nodes, bones, and lungs. However, there are reports about the spread of this type of cancer to other parts of the body. Although most patients are diagnosed when the tumor is localized to the prostate, in about 25% of patients, the disease is diagnosed when metastasis has occurred. Some markers can assist physicians in the diagnosis of this disease, such as the Prostate Health Index and the 4 K score. Key Clinical Message: The diagnosis of prostate cancer should be considered in all age ranges of adult men. The long‐distance metastasis might cause unusual presentations of the disease, such as neurologic, musculoskeletal, and dermatologic symptoms and signs far from the origin of the cancer, before genitourinary manifestations. It is crucial to keep the diagnosis of prostate cancer in mind for men with suggestive signs and symptoms that are not usually detected in this disease. [ABSTRACT FROM AUTHOR]

Chronic obstructive pulmonary disease (COPD) is a major public health concern, affecting estimated 164 million people worldwide. Early detection and intervention strategies are essential to reduce the burden of COPD, but current screening approaches are limited in their ability to accurately predict risk. Machine learning (ML) models offer promise for improved accuracy of COPD risk prediction by combining genetic and electronic medical record data. In this study, we developed and evaluated eight ML models for primary screening of COPD utilizing routine screening data, polygenic risk scores (PRS), additional clinical data, or a combination of all three. To assess our models, we conducted a retrospective analysis of approximately 329,396 patients in the UK Biobank database. Incorporating personal information and blood biochemical test results significantly improved the model's accuracy for predicting COPD risk, achieving a best performance of 0.8505 AUC, a specificity of 0.8539 and a sensitivity of 0.7584. These results indicate that ML models can be effectively utilized for accurate prediction of COPD risk in individuals aged 20 to 50 years, providing a valuable tool for early detection and intervention. [ABSTRACT FROM AUTHOR]

Background: Essential tremor (ET) is a neurological disease characterized by action tremor in upper arms. Although its high heritability and prevalence worldwide, its etiology and association with other diseases are still unknown. Method: We investigated 10 common spinocerebellar ataxias (SCAs), including SCA1, SCA2, SCA3, SCA6, SCA7, SCA8, SCA12, SCA17, SCA36, dentatorubral-pallidoluysian atrophy (DRPLA) in 92 early-onset familial ET pedigrees in China collected from 2016 to 2022. Result: We found one SCA12 proband carried 51 CAG repeats within PPP2R2B gene and one SCA3 proband with intermediate CAG repeats (55) with ATXN3 gene. The other 90 ET probands all had normal repeat expansions. Conclusion: Tremor can be the initial phenotype of certain SCA. For early-onset, familial ET patients, careful physical examinations are needed before genetic SCA screening. [ABSTRACT FROM AUTHOR]

Background: The prevalence of colorectal cancer (CRC) among young individuals is rising worldwide, especially in Malaysia. Investigations are currently employed to distinguish the features of young-onset CRC (YOCRC) from adult-onset CRC (AOCRC). This study aimed to compare the characteristics of patients with YOCRC and AOCRC diagnosed at Hospital Universiti Sains Malaysia (HUSM). Methods: This was a retrospective study of CRC cases from January 2013 to December 2021. The details of YOCRC (< 50 years old) and AOCRC (≥ 50 years old) patients were retrieved from the laboratory system and medical records. The Pearson's chi-square test, Fisher's exact test and multiple logistic regression were used to compare the AOCRC and YOCRC cases. Statistical significance was defined at a P-value of ≤ 0.05. Results: The AOCRC (254/319, 79.6%) was more prevalent than YOCRC (65/319, 20.4%), with a predominance of males (53.9%) and Malay sub-population (90.2%). AOCRC and YOCRC shared similarities in left-sided location, high occurrence of adenocarcinoma with moderately differentiated histology and advanced stage of diagnosis. More patients with YOCRC (23.1%) had a family history of cancer than patients with AOCRC. YOCRC also differed from AOCRC by having more specific histological subtypes, such as mucinous adenocarcinoma (15.4%) and signet ring carcinoma (6.2%). In addition, patients with YOCRC commonly presented with a low density of tumour-infiltrating lymphocytes (TILs) (60%). Multiple logistic regression showed a family history of CRC (adjusted odds ratio [AOR] = 3.75, P = 0.003) and histological type (AOR = 15.21, P < 0.001) are more likely to cause YOCRC than diabetes (AOR = 0.06, P < 0.001) and hypertension (AOR = 0.14, P < 0.001) comorbidities, which are associated with AOCRC. Conclusion: Our descriptive study presented the epidemiological and histopathological characteristics of AOCRC and YOCRC in HUSM, providing current information on distinguishing features between the groups. [ABSTRACT FROM AUTHOR]

Background: We aim to present incidence rates and geographical distribution of most common early-onset gastrointestinal cancers (EOGICs), including early-onset esophageal cancer (EOEC), gastric cancer (EOGC) and colorectal cancer (EOCRC) in Iran, 2014- 2018. Methods: Data on new cases of EOEC, EOGC and EOCRC were obtained from publicly available annual reports of the Iranian National Population-based Cancer Registry (INPCR). Incidence rates were calculated using the population data available from the Statistical center of Iran. We considered the World standard population for calculation of age-standardized incidence rates (ASR). We also calculated 95% confidence intervals (CIs) for ASR. All rates are presented per 100 000 person-years. Results: Overall, 19,679 new cases of EOGIC were registered by the INPCR between 2014 and 2018. The ASRs (95% CI) of EOEC, EOGC and EOCRC were 0.49 (95% CI: 0.47-0.51), 1.67 (1.63-1.71), and 3.07 (3.01-3.13) per 100,000 person-years, respectively. Our findings indicate decreasing and constant trends in the ASR of EOEC and EOGC during the study period, 2014-2018. There was an increasing trend in the ASR of EOCRC. We also found geographical disparities in the incidence rates of EOGICs across provinces of Iran, suggesting the highest ASRs of EOEC in Golestan (1.3), EOGC in Ilam (2.99) and EOCRC in Ilam (4.49). Conclusion: Our findings suggested that the incidence rate of EOCRC is consistently increasing. We also found variations in the incidence of EOGICs among different provinces. Further investigations are recommended to clarify the time trends and risk factors of EOGICs in Iran. [ABSTRACT FROM AUTHOR]

Background: Colorectal cancer is the third most common and second deadliest cancer globally. Increasingly, early‑onset colorectal cancer is diagnosed in those under 50 years, leading to some countries advising screenings from ages 40 or 45 years. The ’position of the tumor, right or left, impacts the characteristics and prognosis of early‑onset colorectal cancer. Objectives: Investigating the 5‑year disease‑free and overall survival and histopathologic nature of left‑ and right‑sided early‑onset colorectal cancer. Design: Retrospective study. Setting: Koc University and VKF American Hospital. Materials (Patients) and Methods: Our population includes patients under 50 years with invasive colon cancer treated in two tertiary Turkish hospitals from 2014 to 2019. Of 178 patients, 74.3% had left‑sided tumors. Sample Size: One hundred and seventy‑eight patients. Main Outcome Measures: Histopathological features of left‑ and right‑sided colorectal tumors, and the 5‑year disease‑free and overall survival rate in patients under 50 years of age. Results: The 5‑year disease‑free survival was higher in right‑sided tumors(78.2% vs. 53.1%), but overallsurvival wassimilar. No significant histopathological differences were noted between left‑ and right‑sided tumors, but right‑sided tumors had more mucinous adenocarcinoma and high microsatellite instability (MSI). Conclusion: Our data did not show a difference in survival between right‑ and left‑sided tumors in the age group <50 years contrary to other published literature. Limitations: Retrospective nature and inclusion of a single center, which usually serves Turkiye population with a higher socioeconomic status. The retrospective nature of the study makes it susceptible to selection bias. The small sample size precludes robust group matching and diminishes the statistical power, increasing the risk of Type II errors. [ABSTRACT FROM AUTHOR]

Introduction: Gait and posture abnormalities are the common disabling motor symptoms in Parkinson's disease (PD). This study aims to investigate the differential characteristics of gait and posture in early-onset PD (EOPD) and late-onset PD (LOPD) using the Kinect depth camera. Methods: Eighty-eight participants, including two subgroups of 22 PD patients and two subgroups of 22 healthy controls (HC) matched for age, sex, and height, were enrolled. Gait and posture features were quantitatively assessed using a Kinect-based system. A two-way analysis of variance was used to compare the difference between different subgroups. Results: EOPD had a significantly higher Gait score than LOPD (p = 0.031). Specifically, decreased swing phase (p = 0.034) was observed in the EOPD group. Although the Posture score was similar between the two groups, LOPD was characterized by an increased forward flexion angle of the trunk at the thorax (p = 0.042) and a decreased forward flexion angle of the head relative to the trunk (p = 0.009). Additionally, age-independent features were observed in both PD subgroups, and post hoc tests revealed that EOPD generally performed worse gait features. In comparison, LOPD was characterized by worse performance in posture features. Conclusions: EOPD and LOPD exhibit different profiles of gait and posture features. The phenotype-specific characteristics likely reflect the distinct neurodegenerative processes between them. [ABSTRACT FROM AUTHOR]

BackgroundRising trends in early-onset colorectal cancer (CRC) burden have been observed, but the distribution and temporal patterns of early-onset CRC attributable to dietary risks remain unclear.ObjectivesThis study aimed to estimate the burden of early-onset CRC attributable to dietary risk factors globally, regionally, and nationally, by age and sex, from 1990 to 2019.MethodsThe absolute number and age-specific rates (ASR) of diet-related early-onset CRC burden, as well as summary exposure value (SEV) of attributable dietary risk factors, were extracted from the Global Burden of Disease (GBD) Study 2019. The temporal changes in the burden between 1990 and 2019 were analyzed by calculating the percentage change in the absolute number of burden and the estimated annual percentage change (EAPC) in ASR of burden. The annualized rates of change (ARC) were calculated to evaluate the variation trend of SEV.ResultsIn 2019, diet-related early-onset CRC caused 30,096 (95% UI: 23,148 to 36,091) death cases and 1,465,755 (95% UI: 1,126,489 to 1,761,661) DALYs worldwide, accounting for 34.8% deaths and 34.4% DALYs of overall early-onset CRC, respectively. Moreover, a diet low in milk (responsible for 16.5% [95% UI: 11.1 to 21.9%] of DALYs in 2019), low in whole grains (15.2% [95% UI: 5.9 to 19.9%]), low in calcium (14.3% [95% UI: 10.7 to 18.9%]), high in red meat (5.3% [95% UI: 1.7 to 9.5%]), high in processed meat (2.5% [95% UI: 0.9 to 4.0%]), and low in fiber (2.3% [95% UI: 0.9 to 4.2%]) were early-onset CRC attributable dietary risk factors. The age-specific DALYs rate of early-onset CRC attributable to each dietary risk factor generally showed an increasing trend globally between 1990 and 2019, except for low intake of fiber (EAPC = −0.57, 95% CI: −0.76 to −0.38). In addition, from 1990 to 2019, males have a higher burden than females and this gap may continue to widen due to the increasing difference between the sexes in most dietary risk factors. Furthermore, dietary risks-attributable early-onset CRC burden has shifted from regions with high socio-demographic index (SDI) to high-middle and middle SDI quintiles with uncontrolled dietary risks.ConclusionEarly-onset CRC remains a concerning issue globally, and effective prevention and modification of dietary risk factors holds great promise to reduce early-onset CRC-related burden. Prioritizing diet improvement for males is critical and urgent for CRC control efforts, particularly for those living in developing countries with ongoing dietary pattern transition.

BackgroundEarly-onset colorectal cancer (CRC), defined as diagnosis before age 50, has increased in recent decades. Although more often diagnosed at advanced stage, associations with other histological and molecular markers that impact prognosis and treatment remain to be clarified. We conducted a systematic review and meta-analysis concerning the prevalence of prognostic and predictive tumor markers for early- vs. late-onset CRC, including oncogene mutations, microsatellite instability (MSI), and emerging markers including immune cells and the consensus molecular subtypes.MethodsWe systematically searched PubMed for original research articles published between April 2013–January 2024. Included studies compared the prevalence of tumor markers in early- vs. late-onset CRC. A meta-analysis was completed and summary odds ratios (ORs) with 95% confidence intervals (CIs) were obtained from a random effects model via inverse variance weighting. A sensitivity analysis was completed to restrict the meta-analysis to studies that excluded individuals with Lynch syndrome, a hereditary condition that influences the distribution of tumor markers for early-onset CRC.ResultsIn total, 149 articles were identified. Tumors from early-onset CRC are less likely to include mutations in KRAS (OR, 95% CI: 0.91, 0.85-0.98), BRAF (0.63, 0.51-0.78), APC (0.70, 0.58-0.84), and NRAS (0.88, 0.78-1.00) but more likely to include mutations in PTEN (1.68, 1.04-2.73) and TP53 (1.34, 1.24-1.45). After limiting to studies that excluded Lynch syndrome, the associations between early-onset CRC and BRAF (0.77, 0.64-0.92) and APC mutation (0.81, 0.67-0.97) were attenuated, while an inverse association with PIK3CA mutation was also observed (0.88, 0.78-0.99). Early-onset tumors are less likely to develop along the CpG Island Methylator Phenotype pathway (0.24, 0.10-0.57), but more likely to possess adverse histological features including high tumor grade (1.20, 1.15-1.25), and mucinous (1.22, 1.16-1.27) or signet ring histology (2.32, 2.08-2.57). A positive association with MSI status (1.31, 1.11-1.56) was also identified. Associations with immune markers and the consensus molecular subtypes are inconsistent.DiscussionA lower prevalence of mutations in KRAS and BRAF is consistent with extended survival and superior response to targeted therapies for metastatic disease. Conversely, early-onset CRC is associated with aggressive histological subtypes and TP53 and PTEN mutations, which may serve as therapeutic targets.