Early Onset Research Articles

Understanding Colorectal Cancer Patient Experiences with Family Practitioners in Canada.

Despite ongoing screening efforts, colorectal cancer (CRC) remains a leading cause of death in Canada. The aim of this study was to better understand the experiences of Canadian CRC patients with their family practitioners (FPs) during and after their CRC diagnosis. Patient-reported data were collected through an online questionnaire to understand their CRC diagnosis experiences and identify potential gaps in care. Various factors contributing to challenges throughout a patient's CRC diagnosis (e.g., delayed CRC diagnosis) were determined using descriptive, qualitative, and inferential analyses. These factors could be targeted to optimize CRC care. This study found that 40.6% of the 175 respondents were unaware of at least one of the following aspects of CRC prior to their diagnosis: early-age onset (EAO), symptoms, and screening procedures. While 84.6% had access to a family physician (FP) before their diagnosis, only 17.7% were diagnosed by FPs. Higher proportions of younger individuals experienced misdiagnoses and felt dismissed compared to older individuals. Only half felt fully informed about their diagnosis when it was explained to them by their FP, while 53.1% had their diagnosis explained in plain language. Transitioning towards patient-centred care would promote pre-diagnosis CRC awareness, address differences in management of CRC care (e.g., dismissal and support), and accommodate for age and health-literacy-related disparities, thereby improving CRC care pathways for patients. Future research should investigate FPs experiences in detecting CRC cases to develop educational resources and recommendations, enhancing early detection and improving patient outcomes (1).

Identifying factors associated with substantially reduced adult height in patients with juvenile idiopathic arthritis: a retrospective cohort study

BackgroundJuvenile idiopathic arthritis (JIA), an autoimmune disease affecting children or adolescents and causing joint or systemic symptoms, reportedly has a negative effect on the patients’ body height. This study aimed to identify factors attributable to substantially reduced adult height (SRAH) in JIA patients.MethodsThis single-center retrospective cohort study included patients from 2009 to 2019 in Taiwan. We collected JIA patients aged > 18 years at enrollment with a definite diagnosis and undergoing regular outpatient clinic follow-up or disease remission. Target height difference (THD), defined by adult height minus mid-parental height, was calculated for each patient. The calculation results yielded two groups, of which positive THD was defined as the optimal height (OH group) and those with THD below two standardized deviations as the SRAH group. Descriptive statistics and logistic regression analysis were used to analyze the data.ResultsOf 92 JIA patients, 57 and 12 were in the OH and the SRAH groups. Earlier disease onset, especially before the six-year-old, was noted in the SRAH group (p = 0.026). The distribution of JIA subtypes differed significantly between the two groups (p < 0.001); enthesis-related arthritis was the commonest subtype in the OH group, and systemic JIA was the commonest in the SRAH group. Half of the patients in the SRAH group had an active disease status at enrollment, which was higher than the OH group (50.0% vs. 21.1%, p = 0.066). More patients in the SRAH group had received orthopedic surgery due to JIA (25% vs. 3.5%, p = 0.034). Multiple logistic regression analysis showed that SRAH was independently related to systemic JIA (OR = 37.6, 95%CI 1.2-1210.5; p = 0.041).ConclusionThe subtype of systemic JIA, with its characteristics of early disease onset and active disease status, was the essential factor that significantly impacted adult height.

Achievements and complications related to final fusion surgery in early onset scoliosis at the end of "traditional dual growing rod mission".

Retrospective cohort study. Assess the outcomes of final fusion in early onset scoliosis patients treated with TDGR, particularly with acceptable coronal and sagittal alignment at the end of their growing age. Early onset scoliosis (EOS) poses challenges due to the need for managing spinal deformities while accommodating trunk growth. The dual growing rod (TDGR) technique, a traditional approach, aims to address these concerns by periodic lengthening until spinal growth ceases. Recent shifts propose observation without immediate implant removal after achieving spinal alignment, raising questions about the necessity of final fusion surgery. This retrospective study included 22 EOS patients treated with TDGR who underwent final fusion surgery. Clinical and radiological data were analyzed, including pre- and post-surgery measurements, complications, surgical approaches, and screw density. Patients (average initial surgery age: 6.9years) exhibited significant reductions in main curve angle (preoperative: 65.8°, pre-fusion: 49.1°, post-fusion: 36.3°) and thoracic kyphosis (preoperative: 47°, pre-fusion: 46.6°, post-fusion: 38.7°). Complications included one surgical site infection and four transient intraoperative neuro-monitoring Impairment. High screw density correlated with lower total correction. Final fusion surgery post-TDGR treatment shows promise in correcting EOS-associated deformities. Surgeons and parents should be aware of the procedure's complexity and potential complications.

Further exploration of cardiac channelopathy and cardiomyopathy genes in stillbirth.

To explore genetic variation including whole genome copy number variation and sequence analysis of 98 genes associated with pediatric or adult cardiomyopathies, cardiac channelopathies, and sudden death in an unexplained intrauterine fetal death cohort. The study population included 55 stillbirth cases that remained unexplained after thorough postmortem examination, excluding maternal, fetal, and placental causes of stillbirth. Molecular karyotyping was performed in 55 cases and the trio exome sequencing approach was applied in 19 cases. The analysis revealed six rare variants with predicted effects on protein function in six genes (CASQ2, DSC2, KCNE1, LDB3, MYH6, and SCN5A) previously reported in cases of stillbirth or severe early onset pediatric cardiac related phenotypes. When applying strict American College of Genetics and Genomics classification guidelines, these are still variants of uncertain significance. Several potentially stillbirth-related genetic variants were detected in our cohort, adding to the growing literature on cardiac phenotype gene variation in stillbirth. However, the mechanisms of action, gene-gene interaction, and contribution of the uterine environment are still to be deciphered. In order to advance our knowledge of the genetics of unexplained fetal death, there is an evident need for international collaboration and field standardization.

Age, GVHD prophylaxis, and timing matter in thrombotic microangiopathy after haematopoietic cell transplantation-Asecondary CIBMTR analysis.

Most reports of risk factors (RF) for developing transplant-associated thrombotic microangiopathy (TA-TMA) and death are derived from paediatric and young adult cohorts, with minimal data on differences in RF and outcomes by age. In this secondary CIBMTR analysis, we used a previously prepared dataset that included all first allogenic haematopoietic cell transplantation (HCT) recipients with malignant or non-malignant diseases between 2008 and 2016. The incidence of TA-TMA 6 months post HCT was similar in children and adults 2.1% and 2.0% respectively. Grade 2-4 acute graft-versus-host disease (aGVHD) was a significant adjusted RF for developing TA-TMA in both children and adults. In adults, additional adjusted RFs for TA-TMA included female sex and black race, and in children an unrelated donor. Compared to a calcineurin inhibitor and sirolimus, other forms of GVHD prophylaxis had an adjusted decreased risk of developing TA-TMA in adults. Adjusted RF for death in those with TA-TMA (n = 652) included age ≥18 years old, early onset of TA-TMA diagnosis (<100 days post HCT), grade 3-4 aGVHD and a performance score of <90 prior to HCT. In this cohort, the incidence of TA-TMA was similar in children and adults, and TA-TMA timing was a newly identified RF for death.

A service evaluation study of the impact of ageless policy in a London inner-city early intervention in psychosis service.

Schizophreniform disorders tend to have an early onset. Early intervention in psychosis (EIP) services aim to provide early treatment, reduce long-term morbidity and improve social functioning. In 2016, changes to mental health policy in England mandated that the primarily youth-focused model should be extended to an ageless one, to prevent ageism; however, this was without strong research evidence. An inner-city London EIP service compared sociodemographic and clinical factors between the under-35 years and over-35 years caseload cohorts utilising the EIP package following the implementation of the ageless policy. Both groups received similar care, despite the younger group having significantly more clinical morbidity and needs. Our results may indicate that service provisions are being driven by policy rather than clinical needs, potentially diverting resources from younger patients. These findings have important implications for future provision of EIP services and would benefit from further exploration.

EFEITOS DO PROGRAMA RECREATIVO DE FUTSAL NA QUALIDADE DE VIDA DE CRIANÇAS OBESAS

Introduction: Childhood obesity is considered the most prevalent chronic disease in the child population, impacting the early onset of associated diseases. These subjects are more susceptible to psychological problems and reduced quality of life, increasing depression rates both in childhood and in adult life. Objective: To verify the effect of recreational futsal programs on the quality of life of overweight and obese children. Methodology: Thirteen overweight and obese boys aged 8-12 years participated in a 12-week recreational futsal program composed of ~80-minute sessions two times a week at an intensity greater than 80% of the maximum heart rate. Quality of life was assessed using the PedsQL 4.0 questionnaire, which assesses physical, emotional, social, and school issues. Results: No significant differences were found for anthropometric variables (P&gt;0.05). The intervention improved the emotional dimension (68.7 ± 15.9 vs. 79.1 ± 18; P=0.03) in overweight and obese boys. Regarding the social dimension (64.4 ± 13.7 vs. 63.7 ± 23.5; P&gt;0.05), physical (68.3 ± 24.6 vs. 75.5 ± 18.7, P&gt;0.05), and school (71.1 ± 22.8 vs.: 72.2 ± 24.2, P&gt;0.05) dimensions, not statistically differences were found (P&gt;0.05). Conclusion: The recreational futsal program was effective in improving the quality of life in the emotional dimension of overweight and obese children.

Shared construction of social pretend play sequences at the kindergarten

Pretend play is usually defined as an activity wherein objects and actions (but also affective expression, at times) are separated from their original meanings. Its developmental appearance is set around the second year of life, and increases dramatically in duration, frequency and quality when play episodes start becoming more complex, both linguistically and interactionally reaching its peak in preschool years. To date, however, little attention has been paid to how social pretend play emerges and develops before the age of three. Our study aims to investigate early spontaneous pretend play interactions between children aged 19 to 28 months attending the same kindergarten. We used micro-analytical coding of video-recorded interactions to explore sequences of interaction where children coordinated their actions to engage in social pretend play with objects. Our analyses showed that co-constructed sequences appeared organised by a turn-alternation structure already at 19 months, and children used embodied and material resources afforded by the sequential organisation of actions to dynamically manage their participation. Although explorative, our results seem in line with previous reports suggesting an early onset of social pretend play developing over a continuum from being predominately an individual activity to progressively becoming a co-constructed endeavour.

Recent Advances in Photodynamic Therapy for Vascular Abnormalities.

Abstract Background: Photodynamic therapy (PDT) is a minimally invasive therapy that was gradually established as a first-line treatment for vascular abnormalities. Its action depends on the appropriate wavelength of light and photosensitizer to produce toxic oxygen species and cause cell death. Objective: Several new clinical improvements and trends in PDT have been described in recent years. The aim of this review is to provide an overview of the current data from clinical trials. Methods: In this review, we introduce and generalize the wavelength, duration, dose, strength, and photosensitizer of PDT for the treatment of vascular abnormalities, such as circumscribed choroidal hemangiomas (CCH), choroidal neovascularization (CNV) and capillary malformation (CM). Results: The systematic review findings indicate that the application of PDT is a safe effective method to treat CCH, CNV and CM. However, PDT also has early onset side effects and late onset side effects. Conclusions: Based on the discussion of the effectiveness of PDT, we conclude that PDT has great potential for clinical use, although PDT has possible side effects.

The myosin chaperone UNC-45 has an important role in maintaining the structure and function of muscle sarcomeres during adult aging.

C. elegans undergo age-dependent declines in muscle organization and function, similar to human sarcopenia. The chaperone UNC-45 is required to fold myosin heads after translation and is likely used for refolding after thermally- or chemically-induced unfolding. UNC-45's TPR region binds HSP-90 and its UCS domain binds myosin heads. We observe early onset sarcopenia when UNC-45 is reduced at the beginning of adulthood. There is sequential decline of HSP-90, UNC-45, and MHC B myosin. A mutation in age-1 delays sarcopenia and loss of HSP-90, UNC-45, and myosin. UNC-45 undergoes age-dependent phosphorylation, and mass spectrometry reveals phosphorylation of six serines and two threonines, seven of which occur in the UCS domain. Additional expression of UNC-45 results in maintenance of MHC B myosin and suppression of A-band disorganization in old animals. Our results suggest that increased expression or activity of UNC-45 might be a strategy for prevention or treatment of sarcopenia.

Somatic burden of attention-deficit/hyperactivity disorder across the lifecourse.

A thorough and comprehensive knowledge base on the extent of comorbidity of attention-deficit/hyperactivity disorder (ADHD) and somatic conditions is needed. We compared the prevalence of a wide range of somatic conditions in individuals with and without ADHD and described sex and lifecourse differences. Individuals with an ADHD diagnosis (N = 87,394) and age and sex-matched individuals without an ADHD diagnosis were identified from a large health claims dataset representative of the general German population, including both primary and specialized care (N = 4.874,754). Results were provided for the full sample as well as stratified for sex and age (<12 years, 13-17 years, 18-29 years, 30-59 years, ≥60 years). The results showed that ADHD is associated with a wide variety of somatic conditions across the entire lifecourse. Specifically neurological disorders such as Parkison's disease (odds ratio [OR]: 5.21) and dementia (OR: 2.23), sleep-related disorders (OR: 2.38) and autoimmune disorders affecting the musculoskeletal, digestive, and endocrine system (fibromyalgia OR: 3.33; lupus OR: 2.17) are strongly and significantly associated with ADHD. Additionally, ADHD is associated with higher occurrence of common acute diseases typically treated by the general practitioner, hinting at an overall general lower health status. Sex differences in somatic comorbidity were not prominent. Age differences, in contrast, stood out: in particular endocrine, cardiovascular, and neurological disorders had an early onset in individuals with compared to individuals without ADHD. This research underlines the high burden of disease due to somatic conditions among individuals with ADHD. The findings indicate the need for preventive measures to reduce comorbidity.

Is there an increased risk of genetic abnormalities in fetuses with congenital heart disease in the setting of growth restriction?

To determine if the presence of fetal growth restriction (FGR) is associated with an increased risk of genetic abnormalities in the setting of congenital heart disease (CHD). This was a retrospective cohort study involving pregnancies that met the following criteria: (i) prenatal diagnosis of CHD, (ii) singleton live-birth, and (iii) genetic testing was performed either pre- or postnatally. Genetic results were reviewed by a clinical geneticist for updated variant classification. Fetal growth was stratified as appropriate for gestational age (AGA) or FGR. Of the total of 445 fetuses that met the study criteria, 325 (73.0%) were AGA and 120 (27.0%) were FGR. Genetic abnormalities were detected in 131 (29.4%) pregnancies. There was a higher rate of genetic abnormalities (36.7% vs. 26.8%, p=0.04), which was driven by aneuploidies (20.8% vs. 8.9%, p=0.0006) in the FGR population. Early onset growth restriction was associated with a higher rate of genetic abnormalities (44.5% vs. 25.9%, p=0.03). The rate of genetic abnormalities was significantly higher in the shunt category as compared to remainder of the cardiac anomalies (62.5% in shunt lesions vs. 24.7%, p<0.00001). The rates of FGR (40.9% vs. 21.4%, p<0.0001) and genetic abnormalities (52% vs. 20.4%, p<0.0001) were significantly higher in the presence of extra-cardiac anomalies (ECA). The presence of FGR in fetal CHD population was associated with underlying genetic abnormalities, specifically aneuploidies. Patients should be appropriately counseled regarding the higher likelihood of a genetic condition in the presence of FGR, early onset FGR, shunt lesions and ECA.

Reduction of DUP in early intervention programmes: No pain… almost no gain.

Considering the negative impact of long duration of untreated psychosis (DUP) on outcome, its reduction has become one of the aims of early intervention programmes. The TIPP programme (Treatment and early Intervention in Psychosis Program) was implemented in 2004 in Lausanne and hoped to reduce DUP, without any specific campaign in this regard, through the provision of accessible and specialized treatment. The aim of this study was to evaluate the evolution of patients' DUP over time and the characteristics of patients with extreme DUP. Clinical follow-up data of 380 patients aged 18-35 years with a first psychotic episode who entered the TIPP programme between 2004 and 2017 were analysed. The evolution of DUP over time as well as referring entities and destination after the programme were assessed. The characteristics of patients with extreme DUPs (>percentile 90) were compared with that of other patients. The mean value of the DUP was 452.11 days with a median of 88 days. DUP decreased only moderately over time. We also observe a decrease in discharges to specialized outpatient care at our university hospital. The main characteristics of patients with extreme DUP were early age of onset of psychosis, diagnosis of schizophrenia and presence of history of psychiatric treatment for other conditions before onset of psychosis. These figures suggest that the DUP has reduced over time but that without specific interventions at this level, this reduction is only moderate.

Evaluation of crankshaft phenomenon after posterior fusion for early onset scoliosis using an inverse trigonometric function: a multicenter retrospective cohort study.

The crankshaft phenomenon (CSP) is a corrective loss after posterior surgery for early onset scoliosis (EOS). However, an accurate method for CSP evaluation has yet to be developed. In this study, we evaluated pedicle screw (PS) length and rotation angle using an inverse trigonometric function and investigated the prevalence of the CSP. Fifty patients from nine institutions (mean age 10.6years, male/female ratio 4:46) who underwent early definitive fusion surgery at ≤ 11years of age were included. The rotation angle was calculated as arctan (lateral/frontal PS length) using radiography. Measurements were taken at the apex and lower instrumented vertebra (LIV) immediate, 2-, and 5-year postoperatively. CSP was defined as a rotation angle progression ≥ 5°. We divided patients into CSP and non-CSP groups and measured the demographic parameters, Risser grade, state of the triradiate cartilage, major coronal Cobb angle, T1-T12 length, T1-S1 length, and presence of distal adding-on (DAO). We compared these variables between groups and investigated the correlation between the measured variables and vertebral rotation. Logistic regression analysis investigated factors associated with CSP. The rotation angle progressed by 2.4 and 1.3° over 5years for the apex and LIV, respectively. CSP occurred in 15 cases (30%), DAO in 11 cases (22%), and CSP and DAO overlapped in 4 cases (8%). In the CSP group, the T1-T12 length was low immediate postoperatively. The rotation angle was negatively correlated with preoperative height (r = -0.33), T1-T12 length (r = -0.35), and T1-S1 length (r = -0.30). A lower preoperative T1-T12 length was associated with CSP (odds ratio: 0.996, p = 0.048). CSP occurred in 30% of patients with EOS who underwent definitive fusion. The presence of CSP was associated with a lower preoperative T1-T12 length. Diagnosis, level IV.

Etiologies underlying subtypes of long-standing type 2 diabetes.

Attempts to subtype, type 2 diabetes (T2D) have mostly focused on newly diagnosed European patients. In this study, our aim was to subtype T2D in a non-white Emirati ethnic population with long-standing disease, using unsupervised soft clustering, based on etiological determinants. The Auto Cluster model in the IBM SPSS Modeler was used to cluster data from 348 Emirati patients with long-standing T2D. Five predictor variables (fasting blood glucose (FBG), fasting serum insulin (FSI), body mass index (BMI), hemoglobin A1c (HbA1c) and age at diagnosis) were used to determine the appropriate number of clusters and their clinical characteristics. Multinomial logistic regression was used to validate clustering results. Five clusters were identified; the first four matched Ahlqvist et al subgroups: severe insulin-resistant diabetes (SIRD), severe insulin-deficient diabetes (SIDD), mild age-related diabetes (MARD), mild obesity-related diabetes (MOD), and a fifth new subtype of mild early onset diabetes (MEOD). The Modeler algorithm allows for soft assignments, in which a data point can be assigned to multiple clusters with different probabilities. There were 151 patients (43%) with membership in cluster peaks with no overlap. The remaining 197 patients (57%) showed extensive overlap between clusters at the base of distributions. Despite the complex picture of long-standing T2D with comorbidities and complications, our study demonstrates the feasibility of identifying subtypes and their underlying causes. While clustering provides valuable insights into the architecture of T2D subtypes, its application to individual patient management would remain limited due to overlapping characteristics. Therefore, integrating simplified, personalized metabolic profiles with clustering holds greater promise for guiding clinical decisions than subtyping alone.

Global modified Delphi consensus on diagnosis, phenotypes, and treatment of SCN8A-related epilepsy and/or neurodevelopmental disorders.

We aimed to develop consensus for diagnosis/management of SCN8A-related disorders. Utilizing a modified Delphi process, a global cohort of experienced clinicians and caregivers provided input on diagnosis, phenotypes, treatment, and management of SCN8A-related disorders. A Core Panel (13 clinicians, one researcher, six caregivers), divided into three subgroups (diagnosis/phenotypes, treatment, comorbidities/prognosis), performed a literature review and developed questions for the modified Delphi process. Twenty-eight expert clinicians, one researcher, and 13 caregivers from 16 countries participated in the subsequent three survey rounds. We defined consensus as follows: strong consensus, ≥80% fully agree; moderate consensus, ≥80% fully/partially agree, <10% disagree; and modest consensus, 67%-79% fully/partially agree, <10% disagree. Early diagnosis is important for long-term clinical outcomes in SCN8A-related disorders. There are five phenotypes: three with early seizure onset (severe developmental and epileptic encephalopathy [DEE], mild/moderate DEE, self-limited (familial) infantile epilepsy [SeL(F)IE]) and two with later/no seizure onset (neurodevelopmental delay with generalized epilepsy [NDDwGE], NDD without epilepsy [NDDwoE]). Caregivers represented six patients with severe DEE, five mild/moderate DEE, one NDDwGE, and one NDDwoE. Phenotypes vary by age at seizures/developmental delay onset, seizure type, electroencephalographic/magnetic resonance imaging findings, and first-line treatment. Gain of function (GOF) versus loss of function (LOF) is valuable for informing treatment. Sodium channel blockers are optimal first-line treatment for GOF, severe DEE, mild/moderate DEE, and SeL(F)IE; levetiracetam is relatively contraindicated in GOF patients. First-line treatment for NDDwGE is valproate, ethosuximide, or lamotrigine; sodium channel blockers are relatively contraindicated in LOF patients. This is the first-ever global consensus for the diagnosis and treatment of SCN8A-related disorders. This consensus will reduce knowledge gaps in disease recognition and inform preferred treatment across this heterogeneous disorder. Consensus of this type allows more clinicians to provide evidence-based care and empowers SCN8A families to advocate for their children.

Attention-deficit/hyperactivity disorder in children with epilepsy: A systematic review and meta-analysis of prevalence and risk factors.

To evaluate the prevalence of and risk factors for attention-deficit/hyperactivity disorder (ADHD) in children with epilepsy (CWE). We conducted a systematic search in PubMed and Embase for the meta-analysis. The pooled prevalence of ADHD was calculated using a random-effects model; subgroup analyses were performed to explore heterogeneity. We collected raw data from articles reporting potential risk factors, which were included in the subsequent risk factor analysis. Forty-six articles met the inclusion criteria for the meta-analysis, which showed a pooled ADHD prevalence of 30.7% in CWE, with a predominance of the inattentive subtype of ADHD; the heterogeneity of prevalence was related to population source/study setting (clinic based, community based, or database based) and method of ADHD diagnosis (with or without clinical review). Risk factors for ADHD in epilepsy included younger age, intellectual/developmental disabilities, a family history of epilepsy, earlier epilepsy onset, absence epilepsy, more frequent seizures, and polytherapy; In contrast, risk factors such as sex, generalized epilepsy or seizures, epilepsy etiology, and electroencephalogram abnormalities were not significantly associated with the occurrence of ADHD. The prevalence of ADHD in CWE is high and several potential risk factors are associated with it. This study contributes to a better understanding of ADHD in epilepsy for screening and treatment. This systematic review summarizes the prevalence of attention-deficit/hyperactivity disorder (ADHD) occurring in children with epilepsy and analyses the risk factors for comorbid ADHD in epilepsy. By reviewing 46 articles, we concluded that the overall prevalence of ADHD in children with epilepsy was 30.7% and that intellectual/developmental disabilities were the most significant risk factor for combined ADHD in children with epilepsy. This study provides a wealth of information on comorbid ADHD in epilepsy, which will help clinicians identify and treat potential ADHD in children with epilepsy in a timely manner.

Research progress and future trends of early-onset gastric cancer

Early onset gastric cancer (EOGC), defined as gastric cancer occurring at a younger age. Early-onset gastric cancer tends to be poorly differentiated and highly malignant. Genetic material and environmental exposure factors may be the main causes of early occurrence of gastric cancer. Prolonging the survival and improving the quality of life of patients with early-onset gastric cancer is our main research goal in the future. This article aims to elaborate on the current research status and progress of EOGC in terms of its clinicopathological characteristics, molecular genetics, microecological environment, prediction methods, treatment plans, and prognosis, while also exploring potential avenues for future research.

Trends, challenges, and reflections on early-onset gastric cancer

Early onset gastric cancer (EOGC), as a distinct type of gastric cancer, has seen a gradually increasing incidence in recent years, imposing significant negative impacts on society and families, and has attracted widespread attention. EOGC presents a series of clinical characteristics, such as a higher prevalence among women, pathological types predominantly being poorly differentiated or undifferentiated, and Lauren classification often being diffuse, making it more prone to distant metastasis. However, the causes and mechanisms of its onset are not yet fully understood. Notably, about 10% of EOGC cases exhibit familial clustering and germline mutations in the Cadherin-1 (CDH1) or α-1 catenin (CTNNA1) genes, known as hereditary diffuse gastric cancer (HDGC). These unique clinical features pose significant challenges for the diagnosis and treatment of EOGC. The core of treatment for early onset gastric cancer focuses on strong efficacy, function preservation, rehabilitation, and social reintegration. Clinically, a multidisciplinary approach and comprehensive treatment are essential, with equal emphasis on physiological and psychological aspects, balancing therapeutic effectiveness with functional outcomes, to benefit more patients with EOGC.

Familial aggregation of sinus node dysfunction indicating pacemaker implantation: A nation-wide cohort study

Abstract Background Rare genetically inherited forms of sinus node dysfunction (SND) have been described but the significance of a family history of SND and the associated prognosis remains unknown. Purpose To investigate the risk of SND indicating pacemaker implantation and mortality in first-degree relatives to patients who received a pacemaker because of SND, and to assess the effect of age of onset on disease risk. Methods This was a nationwide retrospective register-based cohort study including all Danish citizens born after 1954. SND was defined to be present when a first pacemaker was implanted on this indication. To establish family structures, we retrieved data from the Danish civil registration registry which contains information on parental links and merged them with the Danish Pacemaker and ICD registry which contains information on all pacemaker implanted because of SND in Denmark. Using Poisson regression, we compared the rates of SND and the risk of all-cause mortality in first-degree relatives of SND patients with the rates in the general population between January 1st 1982 and August 31st 2022. Analyses were adjusted for selected diagnosis- and procedure codes from the Danish National Patient Registry, including hypertension, diabetes mellitus, heart failure, coronary artery disease, atrial fibrillation or flutter, valvular heart disease, stroke, and cardiac surgery. Results We included 6,027,090 individuals among whom 2,477 first pacemakers were implanted due to SND in the time period. The adjusted rate ratio (RR) of SND was 2.9 (95% CI 2.4-3.6), p&amp;lt;0.001, for individuals having any father, mother or sibling with SND compared with the general population. This risk was increased in first-degree relatives across all ages of SND onset in the index person but substantially higher if SND onset in the index person occurred ≤50 years (adjusted RR=7.1 (95% CI 3.5-14.3), p&amp;lt;0.001). Comparable risks of SND were observed for first-degree relatives to mothers, fathers and siblings with SND as well as for men and women. Overall, mortality was similar between individuals having any father, mother or sibling with SND and the general population (adjusted RR=1.02 (0.97-1.08), p=0.45). However, there was a trend towards an increased mortality among first-degree relatives to index persons with an early onset. Conclusions First-degree relatives to SND patients are at increased risk of SND with risk being inversely associated with age of onset in the index person. Overall, mortality in first-degree relatives was comparable to the general population, suggesting a benign prognosis in the vast majority of cases with genetically inherited SND.Table 1Figure 1