Cognitive Ability in Pediatric-Onset Multiple Sclerosis: A Case Series.

: To evaluate the quality of life (QOL) of patients with chronic intestinal pseudo-obstruction (CIPO) before and after treatment. : This study enrolled 50 adult patients diagnosed with CIPO at 4 institutions, of whom 42 underwent therapy. Patient background, body mass index, treatment, palliative care intervention, numerical rating scale for abdominal pain or bloating, the medical outcomes study 36-item short-form health survey (SF-36) and summary scores (physical component summary, mental component summary, and role/social component summary), Japanese version of the Patient Assessment of Constipation Quality of Life (JPAC-QOL) and subscales (physical discomfort, psychosocial discomfort, worries and concerns, and satisfaction), and Patient Assessment of Constipation Symptoms (PAC-SYM) and subscales (stool, rectal, and abdominal symptoms) were prospectively sampled and collected. : The patients (n = 50; 35 females and 15 males) had an average age of onset of 44.7 years and, body mass index of 17.3 kg/m², and 38 (76%) required palliative care intervention. Effective therapeutic interventions included intestinal sterilization (19/42), decompression therapy with percutaneous endoscopic gastrojejunostomy (PEG-J) (6/42), and dietary restriction (6/42). The numerical rating scale for abdominal distension and pain decreased significantly after treatment. All SF-36 summary scores showed improvements. The JPAC-QOL and PAC-SYM both showed improvement overall and in all subscales. : Patients with CIPO have a lower physical, psychological and social QOL, which is equivalent to or lower than that of adult patients with inflammatory bowel disease or psychiatric disorders. Sterilization of the intestinal tract and PEG-J decompression effectively improve the QOL of patients.

Many adult patients with hand eczema report having noticed the first signs of their skin condition at ayoung age. The pathogenesis of hand eczema is multifactorial. In children or teenagers, atopic predisposition as well as skin irritation or contact sensitization play amajor role in hand eczema development. To provide effective counseling to adolescents with hand eczema who are about to choose acareer, it is helpful to know the current state of knowledge regarding hand eczema in this special group of patients. Overview on the factors that are important for hand eczema in teenage patients, as well as possible approaches to career counseling. Evaluation of the current literature on hand eczema in childhood and adolescence and the recommendations for career counseling. The average age of onset for hand eczema is about 12years. The 1‑year and lifetime prevalence in childhood are described as 5.2-10% and 6.5-13.3%, respectively, and 12.1% and 18.3% in adolescents and young adults. Trigger factors differ within the young patient groups: while among children they are often found in the context of leisure activities and hobbies, in adolescents they sometimes relate to an occupational context. The choice of profession does not necessarily have to be restricted even in the context of aprevious history of eczema or an atopic preposition. It is crucial to counsel the young patients in detail, educating them about the special needs of their skin as well as on consistent moisturizing and skin protection. Early identification of trigger factors as well as good counseling and treatment optimization are essential for adolescent hand eczema patients in order to keep the influence of hand eczema on their development, thriving, and career choices as low as possible.

Understanding the natural landscape of the chronology of major depressive disorder and mania in youth

Background: The treatment of juvenile myoclonic epilepsy (JME) is limited, with most patients requiring long-term medication and over half experiencing seizure recurrence upon drug withdrawal. As a third-generation antiseizure medication, brivaracetam (BRV) has emerged as a promising therapeutic option. Its efficacy has been investigated in focal epilepsies and genetic generalized epilepsies (GGEs), with promising results. Objectives: This study aims to evaluate the safety and preliminary efficacy of BRV as an off-label initial monotherapy in patients with newly diagnosed JME, with a specific focus on the control of myoclonic seizures. Design: A prospective, single-center, and observational study. Methods: This study prospectively enrolled drug-naïve patients with JME. All participants received BRV monotherapy. Clinical data were collected at baseline and after a 6-month follow-up period, including demographic characteristics, electroencephalography (EEG), cranial magnetic resonance imaging (MRI), and comprehensive neuropsychological assessments. Changes in seizure frequency, cognitive function, levels of anxiety and depression, sleep quality, and quality of life from baseline to the 6-month follow-up were analyzed and compared. Results: A total of 19 patients were included with a mean age of 20.26 ± 6.88 years (median: 18, interquartile range: 8), and a male-to-female ratio of 12:7. The average age of onset was 14.58 ± 3.42 years, and the average duration of epilepsy prior to BRV treatment was 5.71 ± 7.40 years (median: 2, interquartile range: 5). The mean frequency of myoclonic seizures at baseline was 38.79 ± 45.60 times per month (median: 10, interquartile range: 86). Eighteen patients (94.73%) experienced both generalized tonic-clonic seizures (GTCS) and myoclonic seizures, one patient only experienced myoclonic seizures, The MRI findings were negative in all patients (100%). The EEG of all patients at baseline was abnormal, revealing 3–5.5 Hz generalized spike-and-wave or polyspike-and-wave discharges. At the 6-month evaluation, all patients achieved seizure-free status ( p < 0.001), neuropsychological assessments also demonstrated significant improvement, including Montreal Cognitive Assessment (MoCA; p < 0.001), Hamilton Anxiety Scale (HAMA; p < 0.001), Hamilton Depression Scale (HAMD; p < 0.001), Pittsburgh Sleep Quality Index (PSQI; p < 0.001), and Quality of Life in Epilepsy-31 (QOLIE-31; p < 0.001). Only one patient complained of poor sleep after BRV administration. Conclusion: This study suggests that BRV may offer promising efficacy, specifically in controlling myoclonic seizures and favorable tolerability as an off-label initial monotherapy for JME patients. While the evaluation of efficacy against GTCS requires longer follow-up, our findings support the potential of BRV as a therapeutic option for JME. Further randomized controlled trials are warranted to validate these observations.

Postoperative surgical site infection (SSI) is a feared complication after posterior thoracolumbar fusion. While management of SSI have been described, its mechanical and clinical impact during the follow-up of posterior thoracolumbar fusion for the management of adult spinal deformity is still imperfectly known. We formulate in this study the hypothesis that occurrence of an SSI during the follow-up of posterior thoracolumbar fusion for the management of adult spinal deformity would have mechanical consequences but not necessarily clinical impact at last follow-up. This study is a retrospective analysis of a prospective single-center database. A total of 124 patients (mean age: 64.8 years) with a mean follow-up period of 3.1 years were included. The analysis included patients who underwent long posterior fixation (>5 levels), including the lumbosacral junction, for spinal deformity correction. Patient demographics and complications were analyzed. In cases of deep SSI, patients underwent surgical revision with debridement and broad-spectrum antibiotic therapy. Patient outcomes were evaluated using the Oswestry Disability Index (ODI), the visual analog scale for lumbar pain (VAS-L), and radicular pain (VAS-R) at baseline and final follow-up. Two subgroups were then compared analysis: patients with a postoperative SSI and patients free of infection. On the whole series, the average number of instrumented vertebral levels was 11.7 (range: 6-18). Deep SSI occurred in 25 patients (20%), with an average onset of 0.4 months postoperatively. Multivariate analysis did not show a significant impact of SSI on clinical score improvement (ODI, lumbar and radicular VAS). However, mechanical complications analysis revealed a rod breakage rate of 28.0% in infected patients compared to 14.14% in infection-free patients (p = 0.033). The hazard ratio for rod fracture in patients with deep infection was 3.02 ([1.11, 8.22], p < 0.05). The occurrence of deep SSI represents a significant risk factor for rod fracture during follow-up. However, it does not significantly impact long-term functional outcomes, such as lumbar or radicular pain improvement. These results may find their interest in patients counselling when a surgical treatment for adult spinal deformity is required. IV; retrospective analysis of a prospective single-center database.

Poodles and poodle cross-breds develop a poorly described dorsal truncal hair coat condition informally called "doodle dysplasia". To characterise the clinical, histopathological and epidemiological features of dorsal melanotrichia in poodles and poodle crosses. Twenty-nine privately-owned poodles and poodle cross-breds with an unidentified cause for dorsal melanotrichia in the United States. Retrospective and prospective case recruitment from private/academic dermatology and general practices, and involved record review, owner questionnaire, and dermatohistopathological analysis between 2019 and 2024. Inclusion criteria were poodles and poodle cross-breds with coat colour changes restricted to the dorsum, with or without other concurrent dermatological lesions or systemic signs. The average age of onset was 4 years. Summer was the most commonly reported season of onset (46% dogs), and recent grooming was noted in 57% of dogs with the information available. The most common pattern and distribution were serpiginous in 67% of dogs, and dorsal thorax and lumbar in 39% of dogs. Additional changes were alopecia and alteration of texture. Of those dogs with resolution, 71% had recurrence of coat colour and texture alterations 12 months or 24 months later. Histopathological changes were overall mild, with the most common being outer root sheath apoptosis and altered pigmentation in follicles, without strong evidence to support a dysplasia. "Doodle dysplasia" is a condition with a possible seasonal and/or environmental component. Given the lack of clear evidence for dysplasia, we propose a new name: dorsal melanotrichia of poodles and poodle crosses.

Muscle onset detection is a fundamental problem in electromyography signal analysis, human-machine interaction, and rehabilitation assessment. In medical and biomedical applications, slow muscle activation onset processes are widely encountered in scenarios such as rehabilitation training, postural regulation, and fine motor control. Such processes are typically characterized by slowly varying amplitudes, long temporal durations, and high susceptibility to noise interference, which poses significant challenges for accurate identification of onset timing. To address these issues, a lightweight temporal attention method for slow muscle activation onset detection is proposed and systematically validated under multimodal experimental settings. The proposed method takes surface electromyography signals as the primary input, while synchronously acquired optical motion image data are incorporated into the experimental design and result analysis, thereby aligning with the common joint use of optical imaging and physiological signals in medical and biomedical research. From a methodological perspective, the proposed framework is composed of lightweight temporal feature encoding, a slow activation-aware temporal attention mechanism, and noise suppression with stable decision strategies. Under the constraint of low computational complexity, the ability to model progressive activation signals is effectively enhanced. Experiments are conducted on a dataset containing multiple types of slow activation movements, and model performance is evaluated using five-fold cross-validation. The results demonstrate that under regular signal-to-noise ratio conditions, the proposed method significantly outperforms traditional threshold-based approaches, classical machine learning models, and several deep learning baselines in terms of onset detection accuracy, recall, and precision. Specifically, onset detection accuracy reaches approximately 92%, recall is around 90%, and precision is approximately 93%. Meanwhile, the average onset detection error and detection delay are reduced to about 41ms and 28ms, respectively, with the false positive rate controlled at approximately 2.2%. Stable performance is further maintained under different noise levels and cross-subject settings, indicating strong robustness and generalization capability.

Cerebrospinal fluid (CSF) is a crucial type of biological specimen for neurosyphilis diagnosis. This study aims to comprehensively analyse the clinical manifestations and risk factors of adverse reactions in syphilis patients following lumbar puncture (LP). A total of 573 syphilis patients who underwent LP examinations between August 2023 and April 2024 at the Department of Sexually Transmitted Diseases, Shanghai Skin Disease Hospital, were selected. The clinical manifestations, onset timing, risk factors, and duration of relief from adverse reactions in these patients undergoing LP were statistically analysed. Among 573 patients diagnosed with syphilis, 142 patients (24.8%) experienced adverse reactions following LP. Factors such as age, needle size, symptoms of paralysis, and the duration of postoperative bed rest were significantly associated with adverse reactions after LP (p < 0.05). Furthermore, age >30 years, the use of a 20G needle, and paralysis symptoms were identified as independent protective factors (p < 0.05), whereas bed rest duration >6 hours contributed to increased risk for adverse reactions (odds ratio [OR] = 3.544, p = 0.010). The average onset time for adverse reactions following LP was 14.34 ± 1.54 hours, while the average duration for resolution of these reactions was 5.52 ± 0.26 days postoperatively. The high incidence of adverse reactions following LP in patients with syphilis poses challenges to restoring quality of life among affected patients. A thorough assessment of risk factors for adverse reactions could inform the selection of appropriate measures to mitigate the occurrence of such reactions.

ABSTRACT Objective This study aims to investigate the relationship between sexual debut age and subsequent marijuana experimentation and regular use. Methods Data from NHANES 2015–2016 was utilized. The study included 3414 participants. Sexual debut age were assessed through the MEC Interview, while marijuana experimentation and regular use were evaluated using the Drug Use Questionnaire. Logistic regression analysis was conducted to examine associations, with RCS curves used to visualize these relationships. Results Among participants who experimented with marijuana, 50.76% transitioned to regular user, with an average onset age of 18.01 ± 5.13 years. Positive associations were found between sexual debut and both marijuana experimentation (OR = 11.911, 95% CI: 6.604–21.744) and regular use (OR = 10.012, 95% CI: 4.335–23.124) after adjusting for covariates. A negative association was observed between sexual debut age and both marijuana experimentation (OR = 0.770, 95% CI: 0.748–0.793) and regular use (OR = 0.734, 95% CI: 0.706–0.763) after adjusting for covariates. Conclusions The study highlights the early age at which individuals begin regular marijuana use and the association between sexual behaviors and marijuana consumption. Furthermore, a delayed sexual debut age is linked to lower rates of marijuana experimentation and regular use.

Multiple sclerosis (MS) is a chronic, immune-mediated disorder that predominantly affects women, with an average age of onset between 20 and 50 years. As a result of the early age of onset and increasing life expectancies of women, owing to improvements in disease-modifying treatments (DMTs), recommendations regarding disease and symptom management may vary depending on their life stage and should be tailored to the individual. In addition, in recent years, new data regarding the management of MS from the preconception to postpartum period has led to evolving recommendations from both neuroimmunologists and national drug agencies alike. Similarly, an aging MS population has led to questions regarding the effect of menopause on MS and guidance regarding DMTs as patients age. The purpose of this review is to provide an up-to-date, comprehensive summary of the clinical course and management of the disease and commonly experienced symptoms during puberty, preconception and pregnancy, postpartum, menopause, and life after menopause.

Quality of life in Epilepsy: a comparison between pediatric and adult onset.

Abstract Auroral kilometric radiation (AKR) provides a sensitive probe of magnetospheric dynamics during substorms. We analyze an extended data set of AKR bursts observed by the WIND spacecraft to investigate how the frequency structure of AKR responds to substorm onset and evolution. A new adaptive method is introduced to identify low and high frequency extensions (LFEs and HFEs) of AKR by defining dynamic frequency thresholds for each substorm individually. Using substorm onset lists derived from both auroral imagery and ground‐based magnetometers, we examine how occurrence rates and integrated power contributions of LFEs and HFEs depend on substorm epoch and magnetic local time (MLT). LFEs and HFEs are most frequently observed near the average substorm onset location (≈23 hr MLT) and within minutes of substorm onset. LFEs show the clearest enhancement, contributing a greater fraction of the total AKR power post‐onset and in the pre‐midnight sector, suggesting that they represent a distinct substorm‐driven component of AKR. In contrast, HFEs show weaker and less systematic responses, with variability consistent with the main AKR band, suggesting that HFEs are an extension of the main band AKR rather than a separate population. Finally, substorm onset times derived from auroral imagery yield a sharper AKR response than those from ground magnetometer lists, underscoring the stronger physical link between aurora and AKR and highlighting limitations of ground magnetometer‐based onset identification. These results demonstrate that frequency extensions of AKR can be used to improve substorm identification.

The problem of depression in patients with multiple sclerosis raises many clinical questions concerning the genesis and clinical manifestations of depression, the relationship between affective manifestations and the form and type of the course of multiple sclerosis, and the mechanisms of formation of suicidal behavior in patients with this pathology. Symptoms of depression are very often observed in MS patients as a patient's reaction to a chronic disease and is short-term, a manifestation of focal brain damage, as well as a consequence of changes in the immunobiochemical profile (cytokines, biogenic amines). Depressive disorders often recede into the background and are often not recognized, since neurological symptoms occupy a leading position in the clinical picture. The purpose of this study is to investigate depressive disorders, as well as the features of their course in patients with multiple sclerosis. Patients and methods. The research included a study group of 113 participants with multiple sclerosis, MacDonald criteria 2005, 2010 (2017 edition), and a comparison group of 45 patients with organic depressive disorder. The A.T. Beck depression scale and the depression self-assessment scale developed at the V.M. Bekhterev National Medical Research Center for Psychiatry and Neurology were used to identify depression. The diagnosis of depressive disorder was established in accordance with the ICD-10 criteria by a psychiatrist. The study used the Spielberger State-Trait Anxiety Inventory (adapted by Yu.L. Khanin) and L.D. Malkova's asthenic state scale (adapted by T.G. Chertova). The group included patients with remitting and secondary progressive types of the disease. Results and discussion. The study included data from dynamic follow-up of 158 patients: the study group consisted of patients with multiple sclerosis with depression 71.5% (113 individuals), of which 61.1% (69 individuals) with a remitting course and 38.9% with a secondary progressive course (44 individuals). The age of the patients at the time of examination ranged from 18 to 60 years, with mean age of 39.7±10.91 years. The majority of patients had a disease duration of less than 20 years, on average 8.23±6.57. The average age of onset of the disease is 30.2±10.5. The study has proved that the diagnosis of asthenia, regardless of the severity of depressive disorder, in patients in the study group corresponds to the values of (60.15±1.35) points, i.e. the asthenia clinical picture. The patients with secondary progressive multiple sclerosis differed in the older age of the disease (50.89 ± 1.97) years, the number of exacerbations (p=0.00094300***), and the level of disability at (5.0±0.24) points (p=0.00000000***) compared with the patients with remitting MS with depression (2.38±0.15). The comparison group of 45 people is represented by patients with organic depressive disorder (F06.32). Their mean age was (35.81±13.57) years. The number of depressive episodes detected in the anamnesis was within (2.3±1.18) cases. A close relationship was established in the factors of patients in the study group between "the duration of the disease" (9.84±0.73), "the number of exacerbations" (3.69±2.27) R=0.54 p&lt;0.001, "asthenia" (60.15±1.35) R=0.31 p&lt;0.001, and "personal anxiety" (52.39±8.6) R=0.23 p&lt;0.05. In the comparison group, the indicator of "age" (32.81±13.57) is directly related to "duration of illness" (4.6±3.86) R=0.32 p&lt;0.01, and "duration of illness" (4.6±3.86) to "number of depressive episodes" (2.3±1.18) R=0.85 p&lt;0.001. In the patients of the study group, the severity of depressive disorders ranges from mild depression at 35.4% (40 individuals) according to Beck's scale to 41.6% (47 individuals) severe depression/moderate depression, whereas in patients in the comparison group, average severity of depressive disorder was in 33.3% of the cases, moderate depression in 53.3%, and severe depression was registered in 13.4%. The study showed significant differences in the manifestations of symptoms of depressive disorders, which are noted in the group of comparison at the level of p&lt;0.001 in terms of "mood" p=0.00009303***, "dissatisfaction" p=0.00007221***, "guilt" p=0.00000001***, "ideas of self-blame" p=0.00000001***, increased "tearfulness" p=0.00005884***, "weight loss" p=0.00087437***, which meets the international criteria for depressive disorders. In turn, the "loss of libido" indicator is higher than p= 0.00033654*** in MS patients of the study group. The patients of the study group and the comparison group experience almost equally "a feeling of punishment", "indecision", "loss of working capacity", increased "fatigue", "loss of appetite", and feeling of being "engulfed by bodily sensations", which indicates the severity of the depressive experience. Conclusion. Depressive disorders are a competing disease in neurological diseases and are statistically recorded in literary sources in different percentage ranges without studying the characteristics of patients' experiences. The data obtained lead to the development of personalized therapy for patients with multiple sclerosis, with the aim of relieving symptoms and improving quality of life.

Free flap reconstruction has become the standard of care in the repair of complex defects of the head and neck; however, surgical site infection remains a key area for improvement. This study aims to better understand the risk factors for surgical site infection in head and neck free flap reconstruction and gain insight into antibiotic prophylaxis choices. This retrospective cohort study reviews data from 100 cases across a 5-year period. Univariate and multivariate analyses have been employed to elucidate statistically significant associations, examining surgical site infection, potential risk factors and other post-operative markers. A surgical site infection developed in 32.0% of cases, with an average onset of 11.3 days post-operation. Preoperative anaemia (OR: 3.259) and a prophylactic antibiotic duration of ≤ 24 h (OR: 3.010) were found to be independently significant risk factors for infection. Furthermore, surgical site infection was found to significantly increase unplanned returns to theatre (p ≤ 0.001), complete flap failure (p = 0.005) and length of stay (p = 0.026). The results also suggest that a 48-h prophylaxis duration may be optimal, with no significant difference in infection rate at this cut-off point. To the author's knowledge, this is the first paper to establish preoperative anaemia as an independently significant risk factor for surgical site infection in head and neck free flap operations. This study also finds the Australian guidelines' recommendation of ≤ 24 h of antibiotic prophylaxis to be potentially inadequate in effectively controlling surgical site infection following head and neck free flap reconstruction.

Evaluation of epilepsy in 8p-related disorders.

Radiological-pathological correlation in encapsulated papillary carcinoma of the breast.

643 Background: The incidence of neuroendocrine tumors (NETs) has increased over the past few decades, especially among younger patients. While data from other gastrointestinal malignancies suggest early-onset may be associated with biological differences, this is yet to be investigated in NETs. We sought to characterize the molecular and immune landscape of early (EO)- versus average-onset (AO) pancreatic (pNETs) and small intestinal NETs (siNETs). Methods: Cases with metastatic pNETs and siNETs sequenced using the Tempus xT assay were included. DNA sequencing was performed to identify somatic alterations and whole transcriptome RNA-seq data were normalized to log2(TPM+1) with assay correction. Immune profiling analysis included tumor mutational burden (TMB), microsatellite instability (MSI), PD-L1 status, and immune infiltration estimated via quanTIseq. Differential expression between EO (&lt;50 years of age at diagnosis) and AO-NETs (&gt;50 years) was assessed using Wilcoxon rank sum tests with Benjamini–Hochberg correction, and pathway enrichment was assessed via GSEA (Gene Set Enrichment Analysis). Statistical significance was defined as p&lt;0.05 and q&lt;0.10 for GSEA. Results: A total of 502 patients were included, of which, 134 had EO-NETs (EO-pNETs=94, EO-siNETs=40). Compared to AO, EO-pNETs had a significantly lower prevalence of KRAS (2.1% vs 14%, p=0.001), TP53 (14% vs 25%, p=0.004), SMAD4 (3.2% vs 12%, p=0.01) and RB1 (6.4% vs 14%, p=0.04) and a higher prevalence of LRP1B (8.5% vs 1.3%, p=0.003) alterations. Among siNETs, EO cohort had a significantly higher prevalence of PAX5 (5% vs 0%, p=0.04) and HDAC2 (5% vs 0%, p=0.04) alterations. On GSEA, EO-pNETs had a significantly higher expression in the VEGF, apical junction, hedgehog signaling, and myogenesis pathways while AO-pNETs had higher expression in MYC, E2F, DNA repair and G2M checkpoint pathways. No significant differences in transcriptomic expression were noted between EO- and AO-siNETs. On immune profiling, EO-pNETs cases were enriched for M2 macrophages (p=0.004) while siNETs displayed no significant age-based differences. TMB-H, MSI-H, and PD-L1 expression did not differ by age in either group. Conclusions: This is the largest molecular analysis comparing EO and AO-enteropancreatic NETs. More age-based differences were seen in pNETs with some changes in EO cases predicting better response to immunotherapy while AO cases attained more alterations found in grade 3 NETs or NECs. Our results suggest that age at diagnosis may be an important determinant of tumor biology and clinical management options.

122 Background: Most mCRC occurs in pts ≥50 y old but increasingly pts &lt;50 y are being diagnosed with mCRC. Evidence regarding their outcomes is conflicting. BREAKWATER (Phase 3; NCT04607421) demonstrated statistically significant and clinically meaningful improvements in ORR, PFS by blinded independent central review (BICR), and OS with encorafenib + cetuximab (EC)+mFOLFOX6 vs control (chemotherapy±bevacizumab) in 1L BRAF V600E-mutant mCRC, making EC+mFOLFOX6 a new standard of care. We report analyses by age. Methods: Eligible pts with untreated BRAF V600E-mutant mCRC were randomized 1:1:1 to EC (n=158; enrollment closed after protocol amendment), EC+mFOLFOX6 (n=236), or control (n=243). Dual primary endpoints (EPs) were ORR and PFS by BICR; the key secondary EP was OS for EC+mFOLFOX6 vs control. Here, exploratory efficacy, safety, and biomarker analyses were performed by age at diagnosis (&lt;50 y, early onset [EOCRC] or ≥50 y, average age onset [AOCRC]). A genAI tool (08/06/25; Pfizer; GPT-4o) assisted with the 1st draft; authors assume content responsibility. Results: As of Jan 6, 2025, 39, 66, and 59 EOCRC pts (~25% of each arm) were enrolled in the EC, EC+mFOLFOX6, and control arms, respectively, with 119, 170, and 184 AOCRC pts in each arm, respectively (Table). Median age (range) was 41 (24, 49) y for EOCRC pts and 64 (50, 84) y for AOCRC pts. Results for EC+mFOLFOX6 in EOCRC and AOCRC pts, respectively, were 69.7% and 64.1% for confirmed ORR by BICR, 10.9 and 14.0 mo for mPFS by BICR, and 23.8 and 30.3 mo for mOS. Results for the control arms in EOCRC and AOCRC pts, respectively, were 45.8% and 34.8% for confirmed ORR by BICR, 7.1 mo in both groups for mPFS by BICR, and 15.1 and 14.9 mo for mOS. See table for EC data. Incidence of grade 3/4 AEs was 80.0% and 82.0% for EC+mFOLFOX6, 64.8% and 67.4% for control, and 35.1% and 44.8% for EC in EOCRC and AOCRC pts, respectively. Biomarker data will be reported. Conclusions: All pts with BRAF V600E-mutant mCRC receiving 1L EC+mFOLFOX6, including EOCRC pts, showed improved ORR, PFS, and OS vs control. The safety profile of EC+mFOLFOX6 was similar for both age groups. Clinical trial information: NCT04607421 . EOCRC EOCRC EOCRC AOCRC AOCRC AOCRC EC n=39 EC+ mFOLFOX6 n=66 Control n=59 EC n=119 EC+ mFOLFOX6 n=170 Control n=184 Confirmed ORR, a % (95% CI) 56.4(41.0, 70.7) 69.7(57.8, 79.4) 45.8(33.7, 58.3) 42.0(33.5, 51.0) 64.1(56.7, 70.9) 34.8(28.3, 41.9) Odds ratio vs control (95% CI) 1.53(0.68, 3.46) 2.73(1.31, 5.68) 1.36(0.85, 2.18) 3.35(2.17, 5.18) Median PFS, a mo(95% CI) 5.4(4.2, 5.7) 10.9(9.7, 16.8) 7.1(6.7, 11.1) 8.3(6.4, 9.2) 14.0(11.3, 16.6) 7.1(5.9, 8.8) HR vs control(95% CI) 1.84(1.08, 3.13) 0.57(0.34, 0.95) 0.94(0.70, 1.27) 0.49(0.37, 0.65) Median OS, mo(95% CI) 18.9(14.6, 23.4) 23.8(21.1, NE) 15.1(13.2, 19.5) 19.5(17.6, 24.5) 30.3(21.0, NE) 14.9(13.7, 18.2) HR vs control(95% CI) 0.68(0.40, 1.16) 0.42(0.25, 0.71) 0.70(0.52, 0.95) 0.51(0.38, 0.68) NE, not estimable. a By BICR.

621 Background: The incidence of early-onset GEP-NETs (EO, &lt;50 years) is rising, with data suggesting better outcomes compared to average-onset (AO, ≥50 years) GEP-NETs. While comorbidities and tumor biology may contribute to these differences, the role of metastatic burden and distribution of metastasis remains unclear. We sought to characterize and compare the clinical profiles of early and average onset GEP-NETs. Methods: We conducted a multicenter retrospective analysis using the TriNetX database, a federated de-identified EMR network. Adults (18–90 years) with GEP-NETs and at least one metastatic site between January 1, 2010, and August 5, 2025, were included. Metastatic sites were identified using ICD codes: lung (C78), lymph nodes (C77), brain (C79.3), retroperitoneum/peritoneum (C78.6), liver (C78.7), and bone (C79.5). EO-GEPNETs were defined as age 18–50 at diagnosis, AO-GEPNETs as ≥51. Propensity score matching (1:1 greedy nearest neighbor, caliper 0.1) was performed for sex, treatments (5-FU, octreotide, lanreotide, everolimus, cabozantinib, sunitinib, temozolomide, lutathera), surgeries (small/large bowel resection, liver resection/lobectomy), and primary site (small bowel, pancreatic, unspecified). Survival analysis was done using kaplan-meier survival estimate. The index event was metastatic disease. Baseline demographics, clinical features, and treatments were collected and compared using t-test statistics. Results: Among 5,438 patients, 961 (17.7%) had EO-GEPNETs. Compared with AO-GEPNETs, EO-GEPNETs had a higher proportion of females (54.5% vs 52.2%, p=0.05), more African Americans (17.2% vs 13.2%, p=0.002), more pancreatic primaries (5.3% vs 3.2%, p=0.002), and fewer small bowel primaries (38% vs 47.8%, p&lt;0.0001). After matching, each cohort included 959 patients. Median overall survival (OS) in AO-GEPNETs was 88 months with 327 deaths (34.1%), whereas EO-GEPNETs did not reach median OS, with 245 deaths (25.5%), (HR 1.50, 95% CI 1.27–1.78; p&lt;0.0001). Metastatic patterns showed modest differences: liver metastases were more frequent in EO-GEPNETs (53.6% vs 48.1%; RR 0.90, 95% CI 0.82–0.98, p=0.02), while bone (16.8% vs 13.8%, p=0.06), lymph node (25.3% vs 25.0%, p=0.88), and lung metastases (9.2% vs 10.7%, p=0.25) were comparable. Peritoneal metastases were slightly higher in EO-GEPNETs (20.3% vs 16.8%; RR 0.83, 95% CI 0.68–0.99, p=0.04). Conclusions: EO-GEPNETs display distinct demographics, greater pancreatic involvement, and modestly higher liver and peritoneal metastases, yet are associated with better overall survival than AO-GEPNETs. Differences in metastatic patterns alone may not account for these disparities, underscoring the need to elucidate biological underpinnings of age-related survival differences.