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Abstract The incidence of early‐onset colorectal cancer (CRC), which affects people under 50, is increasing for unknown reasons. Additionally, no underlying genetic cause is found in 20%–30% of patients suspected of having familial CRC syndrome. Whole exome sequencing (WES) has generated evidence for new genes associated with CRC susceptibility, but many patients remain undiagnosed. This study applied WES in five early‐onset CRC patients from three unrelated families to identify novel genetic variants that could be linked to rapid disease development. Furthermore, the candidate variants were validated using Sanger sequencing. Two heterozygote variations, c.1077‐2A>G and c.199G>A, were found in the MSH2 and the MLH1 genes, respectively. Sanger sequencing analysis confirmed that these (likely) pathogenic mutations segregated in all the affected families' members. In addition, we identified a rare heterozygote variant (c.175C>T) with suspected pathogenic potential in the MAP3K1 gene; formally the variant is of uncertain significance (VUS). Our findings support the hypothesis that CRC onset may be oligogenic and molecularly heterogeneous. Larger and more robust studies are needed to understand the genetic basis of early‐onset CRC development, combined with novel functional analyses and omics approaches.

Abstract 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 Background The incidence of colorectal cancer is increasing among young adults and more rectal cancers are reported. This study aimed to identify the clinical features specific for early‐onset rectal cancer and provide insights on cancer management. Methods Early‐onset (

Abstract Background The incidence of early‐onset prostate cancer (PCa) has increased significantly over the past few decades. It is necessary to develop a prognostic nomogram for the prediction of overall survival (OS) in early‐onset PCa patients. Methods A total of 23,730 early‐onset PCa patients (younger than 55 years old) between 2010 and 2015 in the Surveillance, Epidemiology, and End Results (SEER) database were enrolled for the current study, and randomly separated into the training cohort and the validation cohort. 361 eligible early‐onset PCa patients from The Cancer Genome Atlas‐Prostate Adenocarcinoma (TCGA‐PRAD) cohort were obtained as the external validation cohort. Independent predictors were selected by univariate and multivariate Cox regression analysis, and a prognostic nomogram was constructed for 1‐, 3‐, and 5‐year OS. The accurate and discriminative abilities of the nomogram were evaluated by the concordance index (C‐index), receiver operating characteristic curve (ROC), calibration plot, net reclassification index (NRI), and integrated discrimination improvement (IDI). Results Multivariate Cox analysis showed that race, marital status, TNM stage, prostate‐specific antigen, Gleason score, and surgery were significantly associated with poor prognosis of PCa. A nomogram consisting of these variables was established, which had higher C‐indexes than the TNM system (training cohort: 0.831 vs. 0.746, validation cohort: 0.817 vs. 0.752). Better AUCs of the nomogram than the TNM system at 1, 3, and 5 years were found in both the training cohort and the validation cohort. The 3‐year and 5‐year AUCs of the nomogram in the TCGA‐PRAD cohort were 0.723 and 0.679, respectively. The calibration diagram, NRI, and IDI also showed promising prognostic value in OS. Conclusions We developed an effective prognostic nomogram for OS prediction in early‐onset PCa patients, which will further assist both the precise clinical treatment and the assessment of long‐term outcomes.

Abstract Background and Aims The annual incidence of early‐onset colorectal cancer (EOCRC) is increasing at an alarming rate. The prognosis of EOCRC remains controversial, and whether the early onset is a risk factor for colorectal cancer remains unclear. Methods We searched four electronic bibliographic databases from database inception to April 25, 2022 for studies that included both early‐ and later‐onset patients and performed a prognostic analysis. Random‐effects models were used to summarize the prognostic information extracted by the investigators, including overall survival (OS), cancer‐special survival (CSS), and disease‐free survival (DFS). Network meta‐analysis (NMA) was used to compare patients' long‐term prognoses in different age subgroups. Results After 694 reports were screened, 13 studies were included in the final analysis, with a total of 448,781 CRC cases. In the meta‐analysis of the 5‐year OS, EOCRC had a better prognosis compared to LOCRC (hazard ratio [HR] 0.87, 95% confidence interval [CI], 0.74–0.99; relative risk [RR] 0.83, 95% CI, 0.78–0.89). No difference in prognosis was found between the two groups in terms of 5‐year CSS (RR 0.99, 95% CI, 0.93–1.05), 5‐year DFS (RR 0.90, 95% CI, 0.74–1.09), and short‐term OS. In the NMA, patients aged

Abstract Young black women are at higher risk of triple‐negative breast cancer (TNBC); however, a majority of the genetic studies on cancer predisposition were carried out in White populations. The underrepresentation of minority racial/ethnic populations in cancer genetic studies may have led to disproportionate gaps in our knowledge of cancer predisposition genes in these populations. We surveyed the protein‐truncating mutations at the exome‐wide scale and in known breast cancer predisposition genes among 170 patients of multiple racial/ethnic groups with early‐onset (≤age 50) TNBC from two independent cohorts. Black patients, on average, had a higher number of truncating mutations than Whites at the exome‐wide level, but fewer truncating mutations in the panel of known breast cancer genes. White TNBC patients showed a strong enrichment of truncating variants in known breast cancer genes, whereas no such enrichment was found among Black patients. Our findings indicate likely more breast cancer disposition genes yet to be discovered in minority racial/ethnic groups, and the current multigene panels may result in unequal benefits from cancer genetic testing.

Objective: To study the maternal and perinatal outcomes in women with severe pre-eclampsia before 28 weeks of pregnancy., Methods: A descriptive study from a tertiary care center. All consecutive women with severe pre-eclampsia withonset before 28 weeks of pregnancy were included. The details were collected in a predesigned structured proforma prospectively., Results: The study cohort included 145 women with a mean maternal age of 26.97 ± 5.36 years (range 19-47 years). The mean duration of prolongation of pregnancy was 13.04 ± 10.57 days (range 1-51 days). A total of 29.7% (n = 43) of women had at least one major adverse maternal outcome, and the most common was HELLP (hemolysis, elevated liver enzymes, low platelet count) syndrome (n = 24,16.6%), followed by eclampsia (n = 12,8.3%). The stillbirth rate was high (n = 103,68.7%), and most occurred in the antepartum period. Of 47 (31.3%) neonates born alive, only eight (17.02%;8/47) survived up to 28 days of life. Fetal growth restriction with Doppler abnormalities and neonatal sepsis were the most common reasons for perinatal mortality., Conclusion: Expectant management should not be considered routinely when the onset of severe pre-eclampsia is before 25 +6 weeks of pregnancy. Between 26 and 27 +6 weeks it can be offered under close monitoring and the perinatal survival depends on the neonatal services available in their facility., (© 2022 International Federation of Gynecology and Obstetrics.)

Background: Sexting is sending, receiving, or forwarding sexually explicit messages, images, or videos through electronic means. Research has examined sexting in high school and college students. This study seeks to add to the existing literature by exploring the nature of pressured or problematic sexting in middle school-aged subjects., Methods: We asked participants in public colleges in Massachusetts, Colorado, and Virginia, to recall their sexting-related experiences in middle and high school. We utilized an online survey tool for data collection. We performed bivariate quantitative statistical analyses to examine attitudinal and behavioral differences, as well as motivations and consequences of adolescent sexting., Results: The study revealed unique patterns of early-onset sexting compared to sexting in later adolescence. Early-onset adolescents typically start sexting before they become sexually active and are at a higher risk for poor outcomes associated with sexting, they are more likely to seek therapy. Early sexting is significantly more pressured than sexting in later adolescence., Conclusions: The study is an important contribution to the existing research on pressured sexting. Exploring pressured sexting at very early ages finds that early sexting activity is more likely pressured, creates more stress than later in life, and hence, it needs attention from school mental health professionals and education programs. The authors suggest that comprehensive sex education, including sexting should begin earlier than middle school to prevent risky online sexual behavior and provide for learning coping mechanisms for adolescents., (© 2022 The Authors. Journal of School Health published by Wiley Periodicals LLC on behalf of American School Health Association.)

Objective: To evaluate the clinical effectiveness of the routine first-trimester screening for preeclampsia (PE) after being implemented in six Catalan maternities., Methods: Participants in the reference group were recruited prospectively between October 2015 and September 2017. Participants in the study group were recruited retrospectively between November 2018 and May 2019, after implementing the screening program. PE risk was assessed between 11 + 0 and 13 + 6 weeks of gestation using the Gaussian algorithm combining maternal characteristics, mean arterial blood pressure, uterine artery pulsatility index, and maternal serum pregnancy-associated plasma protein-A. Women with a risk ≥1/137 were prescribed daily salicylic acid (150 mg) until 36 weeks of gestation., Results: Preterm PE occurred in 30 of 2641 participants (1.14%) in the reference group, as compared with 18 of 2848 participants (0.63%) in the study group (OR: 0.55; 95% CI, 0.31-0.99; P = 0.045). In the reference group, 37 participants (1.40%) were admitted to ICU, as compared with 23 participants (0.81%) in the study group (OR: 0.57; 95% CI, 0.34-0.96; P = 0.035)., Conclusion: The routine first-trimester PE screening can be implemented in a public healthcare setting, leading to a significant reduction in the incidence of preterm PE and of maternal ICU admission., (© 2022 International Federation of Gynecology and Obstetrics.)

Objective: The aim of this study was to collect prospective national data on early-onset eating disorders (EOEDs) in children in Australia to document changes in clinical presentations, medical complications, management, and incidence since initially described in 2002-2005., Method: Each month pediatricians reported children aged 5-13 years newly diagnosed with an eating disorder to the Australian Paediatric Surveillance Unit and provided de-identified clinical data., Results: Between 2016 and 2018, 184 children were confirmed with EOED with a minimum estimated national incidence of 2.79 per 100,000 children aged 5-13 years (95% confidence interval [CI] 2.40-3.23), nearly double the previously recorded incidence. The mean age at diagnosis was 12.2 years; 43(24%) were boys who were younger than girls (11.85 vs. 12.33 years; p = .03). All had food avoidance. Common symptoms included fear of weight gain 140 (76%), preoccupation with body weight 134 (73%), and misperception of body size 116 (63%). Bradycardia was present in 83 (45%) and 117 (64%) who required hospital admission. The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, Text Revision (DSM-5) criteria for anorexia nervosa were met for 144 (78%)., Discussion: Children with eating disorders continue to present with severe illness. Near doubling in incidence in just over a 10-year period highlights the need for increased clinical resourcing and comparable international data., Public Significance: The incidence of new presentations of eating disorders in children aged 5-13 years has nearly doubled since a similar study was conducted over 10 years ago. Children were unwell for an average of 8 months before diagnosis; approximately 80% had a clear diagnosis of anorexia nervosa and 64% needed hospital admission due to medical complications. This highlights the need for improvements in education and clinical resources for this age group., (© 2022 The Authors. International Journal of Eating Disorders published by Wiley Periodicals LLC.)

Objective: Given that the onset of diseases including colorectal cancer precursors is affecting younger individuals and that obesity is an important risk factor for early-onset, we conducted a study to explore the biochemical profile of differences in serum between early-onset patients and late-onset colorectal precancerous lesions., Methods: A total of 1447 patients, including 469 early-onset patients and 978 late-onset patients, were enrolled from the First Affiliated Hospital of Nanchang University (FAHNU), of which there were 311 sessile serrated adenoma/polyps (SSA/P) and 1136 normal adenomas. The distribution of the included categorical variables was compared via Pearson's chi-squared test, whereas continuous variables were compared by using the nonparametric Kruskal-Wallis test and ANOVA., Results: Compared with late-onset patients, the levels of total bilirubin and HDL-C were lower (p < 0.05), whereas triglyceride and uric acid levels were higher, in early-onset patients. Interestingly, in the subgroup analysis, triglyceride and uric acid levels remained at higher levels, whereas HDL-C remained at lower levels, in early-onset patients than in late-onset patients. Other characteristics, such as LDL-C, drinking, γ-GT, and the N/L ratio, were similar between the two groups. An additional analysis of the association of tumor size with markers showed that lower levels of HDL-C and higher levels of uric acid were associated with increased tumor size (p < 0.05)., Conclusions: Early-onset CRC precursor cases exhibit higher levels of triglycerides and lower levels of HDL-C than late-onset cases. Additionally, levels of HDL-C are negatively associated with tumor size, whereas uric acid was positively correlated with tumor size., (© 2022 The Authors. Journal of Clinical Laboratory Analysis published by Wiley Periodicals LLC.)

Early-onset psychosis disorders are serious mental disorders arising before the age of 18 years. Here, we investigate the largest neuroimaging dataset, to date, of patients with early-onset psychosis and healthy controls for differences in intracranial and subcortical brain volumes. The sample included 263 patients with early-onset psychosis (mean age: 16.4 ± 1.4 years, mean illness duration: 1.5 ± 1.4 years, 39.2% female) and 359 healthy controls (mean age: 15.9 ± 1.7 years, 45.4% female) with magnetic resonance imaging data, pooled from 11 clinical cohorts. Patients were diagnosed with early-onset schizophrenia (n = 183), affective psychosis (n = 39), or other psychotic disorders (n = 41). We used linear mixed-effects models to investigate differences in intracranial and subcortical volumes across the patient sample, diagnostic subgroup and antipsychotic medication, relative to controls. We observed significantly lower intracranial (Cohen's d = -0.39) and hippocampal (d = -0.25) volumes, and higher caudate (d = 0.25) and pallidum (d = 0.24) volumes in patients relative to controls. Intracranial volume was lower in both early-onset schizophrenia (d = -0.34) and affective psychosis (d = -0.42), and early-onset schizophrenia showed lower hippocampal (d = -0.24) and higher pallidum (d = 0.29) volumes. Patients who were currently treated with antipsychotic medication (n = 193) had significantly lower intracranial volume (d = -0.42). The findings demonstrate a similar pattern of brain alterations in early-onset psychosis as previously reported in adult psychosis, but with notably low intracranial volume. The low intracranial volume suggests disrupted neurodevelopment in adolescent early-onset psychosis., (© 2020 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

Background: Controversy exists regarding anticoagulation management following acute cardioversion in patients with early-onset (<48 hours) atrial fibrillation without class I guideline indication for long-term oral anticoagulation (CHA2DS2-VASc 0-1)., Methods and Results: A random-effect meta-analysis of observational studies reporting 30-day incidence of thromboembolic complications after cardioversion without post-procedural oral anticoagulation therapy in patients at low-moderate thromboembolic risk (CHA2DS2-VASc 0-1) was performed. Four studies were included, encompassing 3276 cardioversions. The analysis revealed that the pooled risk of 30-day incidence of thromboembolic complications in this subset of patients is low (0.10%, 95% confidence interval: 0.00%-0.30%)., Conclusions: Given these data, considering the bleeding risk unavoidably conferred by OAT, which is known to be higher in the first month from treatment onset, short-term anticoagulation limited to 4 weeks post-cardioversion of early-onset (<48 hours) atrial fibrillation in patients with low-moderate risk of stroke (CHA2DS2-VASc 0-1) may be omitted, at least in patients with high-bleeding risk., (© 2020 Stichting European Society for Clinical Investigation Journal Foundation. Published by John Wiley & Sons Ltd.)

Objective: To determine the cutoff of antithrombin activity for predicting the interval from diagnosis of early-onset pre-eclampsia to delivery., Methods: At Hokkaido University Hospital, Japan, data were retrospectively assessed on antithrombin activity measured at both diagnosis of pre-eclampsia and delivery among women with singleton pregnancy and pre-eclampsia (defined by combined gestational hypertension and proteinuria) between 2009 and 2017. The timing of delivery was determined by maternal and fetal well-being., Results: Among 2904 singleton deliveries, antithrombin activity was measured for 94 (3.2%) women diagnosed with pre-eclampsia. The median (range) interval was significantly longer for 38 (40%) women with early-onset than for 56 (60%) women with late-onset pre-eclampsia (6.5 [0-27] vs 1 [0-29] days, respectively; P<0.001). In the early-onset group, median antithrombin activity at diagnosis was significantly lower for 19 women with an interval of less than 7 days (72% [60%-92%]) than for 19 women with a longer interval (≥7 days) (84% [59%-110%]; P=0.012). Antithrombin activity of 78% at diagnosis of early-onset pre-eclampsia was optimal for predicting a delivery interval of less than 7 days., Conclusion: A cutoff of 78% antithrombin activity at diagnosis of early-onset pre-eclampsia might be used as a predictor of delivery within 7 days., (© 2019 International Federation of Gynecology and Obstetrics.)

Introduction: This study aimed to investigate the incidence of neonatal early-onset group B streptococcal (GBS) infection in Sweden after promulgation of guidelines (2008) for risk factor-based intrapartum antibiotic prophylaxis, and evaluate the presence of risk factors and obstetric management in mothers., Material and Methods: National registers were searched for infants with early-onset GBS infection during 2006-2011. Medical records of cases and case mothers were abstracted. Verified cases of sepsis/meningitis and cases with clinical sepsis/pneumonia were documented, as well as risk factors in case mothers and timeliness of intrapartum antibiotic prophylaxis administration., Results: There were 227 cases with verified infection, with an incidence of 0.34‰ of live births during the whole period. There was a significant decrease after promulgation of guidelines, from 0.40 to 0.30‰ [odds ratio (OR) 0.75, 95% confidence interval (CI) 0.57-0.99]. A significant decrease in the number of cases with clinical GBS sepsis/pneumonia was also observed. In parturients with one or more risk factors, the incidence of any GBS infection was reduced by approximately 50% (OR 0.47, 95% CI 0.35-0.64), although there were many cases where the opportunity for timely administration of intrapartum antibiotic prophylaxis was missed. In infants of mothers without risk factor(s) there was no reduction in early-onset GBS morbidity. The mortality in verified cases was 4.8% (95% CI 2.1-7.6)., Conclusions: The introduction of national guidelines for risk-based intrapartum antibiotic prophylaxis coincided with a significant 50% risk reduction of neonatal early-onset GBS infection in infants of parturients presenting with one or more risk factors. A stricter adherence to guidelines could probably have reduced the infant morbidity further., (© 2017 Nordic Federation of Societies of Obstetrics and Gynecology, Acta Obstetricia et Gynecologica Scandinavica.)

Objective: Unlike adolescents with adolescent-onset (AO) disruptive behavior, adolescents with early-onset (EO) disruptive behavior may not benefit from treatment., Method: Using Symptom Checklist (SCL-90-R) ratings at admission and discharge of adolescent inpatients with EO (n = 85) and AO (n = 60) disruptive behavior treatment outcome was determined by (a) a change in mean scores and (b) the Reliable Change Index. For a subgroup, ratings on the Satisfaction Questionnaire Residential Youth Care for Parents (n = 83) were used to verify the treatment outcome., Results: Inpatients with EO disruptive behavior had a higher risk of dropout (44.4%) from treatment than the AO group (24.7%). Among the treatment completers, both onset groups reported improvements on the SCL-90-R, with 26.9% recovering and 31.7% improving. Inpatients who reported improvement were mostly rated as improved by their parents (r = .33)., Conclusion: As EO inpatients are more likely to drop out, interventions should aim at motivating youngsters to continue treatment, particularly given the poor outcome in this group. Treatment may benefit both groups because those EO youths who stayed in treatment improved to the same extent as AO inpatients., (© 2016 Wiley Periodicals, Inc.)

Background and Purpose: This study investigates 36 subjects aged 55-65 from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database to expand our knowledge of early-onset (EO) Alzheimer's Disease (EO-AD) using neuroimaging biomarkers., Methods: Nine of the subjects had EO-AD, and 27 had EO mild cognitive impairment (EO-MCI). The structural ADNI data were parcellated using BrainParser, and the 15 most discriminating neuroimaging markers between the two cohorts were extracted using the Global Shape Analysis (GSA) Pipeline workflow. Then the Local Shape Analysis (LSA) Pipeline workflow was used to conduct local (per-vertex) post-hoc statistical analyses of the shape differences based on the participants' diagnoses (EO-MCI+EO-AD). Tensor-based Morphometry (TBM) and multivariate regression models were used to identify the significance of the structural brain differences based on the participants' diagnoses., Results: The significant between-group regional differences using GSA were found in 15 neuroimaging markers. The results of the LSA analysis workflow were based on the subject diagnosis, age, years of education, apolipoprotein E (ε4), Mini-Mental State Examination, visiting times, and logical memory as regressors. All the variables had significant effects on the regional shape measures. Some of these effects survived the false discovery rate (FDR) correction. Similarly, the TBM analysis showed significant effects on the Jacobian displacement vector fields, but these effects were reduced after FDR correction., Conclusions: These results may explain some of the differences between EO-AD and EO-MCI, and some of the characteristics of the EO cognitive impairment subjects., (Copyright © 2015 by the American Society of Neuroimaging.)