Search

Simple Summary: The PELICan hypothesis speaks to the role of perinatal and early life stressors (including malnutrition) in the causation of young-onset cancers. To date, there is no evidence correlating perinatal malnutrition and the risk of young-onset cancer. The Great Famine of China was a significant event in human history. The present study compared the incidence of young-onset cancers in individuals born during and just after the famine to those born prior to the famine. Perinatal exposure to famine, especially in females, was associated with a higher risk of young-onset cancer. This was particularly evident for young-onset genitourinary cancers. Background/Objectives: Perinatal exposure to malnutrition has been hypothesised to influence the development of young-onset cancer (≤50 years of age). This study aimed to determine if perinatal malnutrition in individuals exposed to the Great Famine of China increased their risk of developing young-onset cancer compared to other individuals born prior to the famine. Subjects/Methods: This cross-sectional study involved 7272 participants from the China Health and Nutrition Survey who were classified into four groups based on birth year: participants born between 1953 and 1955 (before the famine) were designated as the pre-famine group (unexposed); the remainder formed perinatal exposure groups comprised of those exposed during the famine (1959–1961), those exposed in the early post-famine period (1962–1964), and those exposed in the late post-famine period (1965–1967). Multivariable adjusted log-binomial regression models were used to calculate the RR and 95% CI of young-onset cancer (including genitourinary cancer) across four groups. Results: Perinatal exposure to early post-famine (RR 2.08; 95%CI 1.04, 4.34; p = 0.043) and the female sex (RR 15.6, 95%CI 4.54, 60.3; p < 0.001) were noted to have a significantly increased risk of young-onset cancer. In addition, the early (RR 13.8; 95%CI 2.68, 253; p = 0.012) and late post-famine (RR 12.3; 95%CI 2.16, 231; p = 0.020) cohorts demonstrated a significantly increased risk of young-onset genitourinary cancer. The latter was accompanied by an increased risk of hypertension (RR 3.30; 95%CI 1.28, 7.87; p = 0.009). Conclusions: Perinatal exposure to famine, especially in females, was associated with a higher risk of young-onset cancer. This was particularly evident for young-onset genitourinary cancers. These findings highlight the potential long-term impact of perinatal malnutrition on young-onset carcinogenesis. [ABSTRACT FROM AUTHOR]

The association between intrauterine growth restriction and cardiovascular disease (CVD) later in life might be confounded by familial factors. We conducted a binational register-based cohort study to assess associations of birth weight for gestational age (GA), a proxy for intrauterine growth restriction, and GA with CVD risk in early adulthood, before and after addressing familial factors via sibling comparison. We included 3,410,334 live nonmalformed singleton births from Sweden (1973–1996) and Denmark (1978–1998). During a median follow-up period of 10 years from age 18 years onwards, 29,742 individuals developed incident CVD (hypertension, ischemic heart disease, or cerebrovascular disease). Compared with individuals born with appropriate birth weight for GA (AGA; 10th–90th percentiles) or full term (39–40 gestational weeks), individuals born severely small for GA (SGA; ≤3rd percentile) or preterm (22–36 weeks) were at increased risk of CVD (hazard ratio (HR) = 1.38 (95% confidence interval (CI): 1.32, 1.45) and HR = 1.31 (95% CI: 1.25, 1.38), respectively). The association was attenuated when comparing individuals born SGA with their AGA siblings (HR = 1.11, 95% CI: 0.99, 1.25) but remained robust when comparing individuals born preterm with their term siblings (HR = 1.21, 95% CI: 1.07, 1.37). Our findings suggest that both SGA and preterm birth are associated with CVD risk in early adulthood, with greater familial confounding noted for SGA birth. [ABSTRACT FROM AUTHOR]

Background: Fetal exposure risk factors are associated with increased autism spectrum disorder (ASD) risk. New hypotheses regarding multigenerational risk for ASD have been proposed, but epidemiological evidence is largely lacking. We evaluated whether parental birth characteristics, including preterm birth and low birthweight, were associated with ASD risk in offspring.Methods: We conducted a nationwide register-based cohort study that included 230 174 mother-child and 157 926 father-child pairs in Denmark. Logistic regression models were used to estimate odds ratios (OR) and 95% confidence intervals (CI) for offspring ASD according to parental preterm (<37 weeks) and low birthweight (<2500 g) status, with or without adjustment for certain grandmaternal sociodemographic factors. Mediation analyses were performed for selected parental and offspring health-related factors.Results: Offspring of mothers or fathers with adverse birth characteristics had about 31-43% higher risk for ASD (maternal preterm birth, OR = 1.31, 95% CI= 1.12, 1.55; maternal low birthweight, OR = 1.35, 95% CI: 1.17,1.57; paternal preterm birth, OR = 1.43, 95% CI = 1.18, 1.73; paternal low birthweight, OR = 1.38, 95% CI= 1.13, 1.70). Parents born very preterm (<32 weeks) marked a nearly 2-fold increase in ASD risk in their children. These associations were slightly attenuated upon adjustment for grandmaternal sociodemographic factors. Mediation analyses suggested that parental social-mental and offspring perinatal factors might explain a small magnitude of the total effect observed, especially for maternal birth characteristic associations.Conclusions: Offspring of parents born with adverse characteristics had an elevated risk for ASD. Transmission of ASD risk through maternal and paternal factors should be considered in future research on ASD aetiology. [ABSTRACT FROM AUTHOR]

Study Question: Is a maternal history of spontaneous abortion (SA) associated with an increased risk of attention-deficit/hyperactivity disorder (ADHD) in offspring?Summary Answer: Our results suggest an association between maternal history of SA and ADHD in offspring, with the risk increasing with the number of maternal SA and highest in the firstborn children whose mothers had had recurrent SAs after adjusting for a number of potential confounders.What Is Known Already: A history of SA has been associated with more complications in next pregnancies and adverse childbirth outcomes, which are risk factors for ADHD in the offspring. However, no previous study has investigated whether maternal SA increases risk of ADHD in the offspring.Study Design, Size, Duration: This population-based study included all live-born children in Denmark from 1 January 1995 to 31 December 2012 (n = 1 062 667). All children were followed from 3 years of age until the day of ADHD diagnosis, death, emigration or 31 December 2016, whichever came first.Participants/materials, Setting, Methods: There were 130 206 (12.2%) children born to mothers who had at least one SA. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs).Main Results and the Role Of Chance: During a median follow-up of 9.4 years (interquartile range, 5.4-14.3), 25 747 children were diagnosed with ADHD. Overall, children of mothers with a history of SA had an increased rate of ADHD (HR, 1.11; 95% CI, 1.07 to 1.15). The HRs increased with the number of maternal SA, 1.09 (95% CI, 1.05 to 1.13) for one SA and 1.22 (95% CI, 1.12 to 1.33) for at least two SAs, respectively. These findings were consistent when we took into consideration a number of factors, such as maternal socioeconomic status, type of SA, birth order, parental history of psychiatric disorders, pregnancy characteristics and adverse birth outcomes.Limitations, Reasons For Caution: Misclassification of SA was possible as we used population-based register data to capture maternal history of SA. However, any misclassification of maternal history of SA would be non-differential with regard to the diagnosis of ADHD in offspring, which generally leads to underestimation of the associations. Furthermore, probabilistic sensitivity analysis suggested that only 1% of change in the estimate may have been due to misclassification of SA.Wider Implications Of the Findings: SA is quite frequent (varying from 15 to 20%), and a small increase of neurodevelopmental problems in offspring could have major public health implications.Study Funding/competing Interest(s): This work was supported by grants from the National Natural Science Foundation of China (No. 81703237, No. 81530086 and No. 81761128035), National Key Research and Development Program (2018YFC1002801, 2016YFC1000505), Shanghai Municipal Commission of Health and Family Planning (No. 2017ZZ02026, No. 2017EKHWYX-02), the Novo Nordisk Foundation (NNF18OC0052029), the Danish Council for Independent Research (DFF-6110-00019), the Nordic Cancer Union (176673, 186200 and R217-A13234-18-S65), Karen Elise Jensens Fond (2016) and Xinhua Hospital of Shanghai Jiao Tong University School of Medicine (2018YJRC03). All authors report no conflict of interest.Trial Registration Number: NA. [ABSTRACT FROM AUTHOR]

Introduction: Mutated tumor suppressor genes (TSG) such as TP53, STK11, and MGA are widely-reported. We hypothesized the presence of single mutation or co-occurring mutations in these specific genes may represent a significant therapeutic target for lung adenocarcinoma.Methods: We sequenced lung adenocarcinoma samples from 677 East-Asian patients, combined them with those from cBioPortal public database (including TCGA) and performed a comparative analysis between Asian and Caucasian populations.Results: East-Asian lung adenocarcinomas presented distinct driver-mutational distribution compared to that of Caucasians (79% vs 56%, p < 0.001). Similar results were observed in TSG mutations of TP53 (35% vs 46%, p = 0.150), STK11 (4% vs 17%, p = 0.006) and MGA (10% vs 4%, p = 0.166). Compared with none-mutational cases, the patients harboring TSG mutations are more likely to be male (p = 0.009), smokers (p < 0.001), and more advanced disease (p = 0.004). In addition, the TSG-mutated tumors had poorer differentiation (p < 0.001), and more likely to be solid or micropapillary-predominant adenocarcinomas (p < 0.001). Survival analysis showed that both overall survival (OS, p < 0.001) and post-recurrence survival (PRS, p < 0.001) became worse with the accumulation of TSG mutations. However, the prognostic variety was not found in Caucasian patients. Moreover, multivariate analysis proved the accumulation of TSG mutations independently predicts both unfavorable OS (HR = 0.435, 95% CI 0.245-0.774, p = 0.005) and PRS (HR = 0.491, 95% CI 0.269-0.894, p = 0.020) in East-Asian patients, adjusting all other survival-associated factors.Conclusions: Co-occurring mutations of specific TSGs define unfavorable subgroups of lung adenocarcinoma, implying that the tumor promotion mechanisms contribute to the heterogeneity in tumor evolution. However, the Caucasian population did not show the same results, providing insights into the molecular basis underlying the striking racial disparities of this disease and evidence for different gene-panel designs for different population in the purpose of targeted therapy. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the changes in dry eye symptoms and clinical signs and corneal sensitivity after small incision lenticule extraction (SMILE) and femtosecond LASIK (femto-LASIK). Design: Prospective, non-randomized comparative study. Methods: The study included a total of 71 eyes of 71 patients; the SMILE group comprised 38 eyes of 38 patients, and the femto-LASIK group comprised 33 eyes of 33 patients. Ocular Surface Disease Index (OSDI), Tear film breakup time (TBUT), the Schirmer test without anesthesia (S1T), corneal fluorescein staining, and central corneal sensation were evaluated before surgery and at 1 week, 1 month, 3 months, and 6 months after surgery. Results: OSDI scores in both groups were increased immediately and returned to preoperative level at 1 month after surgeries. The TBUT values in both groups were reduced after surgeries relative to their preoperative scores. Patients in SMILE group were less likely to have corneal staining compared with those in the femto-LASIK group ([odds ratio] OR = 0.50, 95% [confidence interval] CI 0.28 to 0.93, P = 0.03). Central corneal sensitivity was decreased at all postoperative time points in both groups. However, the central corneal sensation scores in the SMILE group were greater than that in the femto-LASIK group at all of the postoperative time points (all P<0.05). Conclusions: SMILE surgeries resulted in a short-term increase in dry eye symptoms, tear film instability, and loss of corneal sensitivity. Furthermore, SMILE surgeries have superiority over femto-LASIK in lower risk of postoperative corneal staining and less reduction of corneal sensation. [ABSTRACT FROM AUTHOR]

Background: Conjunctival autograft transplantation (CAT) and amniotic membrane transplantation (AMT) are two widely used techniques for pterygium treatment. However, previous studies comparing the outcomes of CAT and AMT have generally had small sample sizes and conflicting results. The aim of this report was to evaluate and comment on peer-reviewed literature for evidence of effectiveness and safety of CAT and AMT for management of pterygium. Methods: Studies comparing outcomes of CAT and AMT for pterygium treatment were identified by searching PubMed, Embase, Web of Knowledge, and a search of all references in relevant papers. Two reviewers confirmed study eligibility and extracted data independently, and data were pooled using standard meta-analysis techniques. Results: Five eligible studies reporting outcomes in 538 eyes were included. The pooled hazard ratio (HR) estimate for recurrence of CAT compared to AMT was 0.30 (95% confidence interval (CI) [0.16, 0.59], p < 0.001) and 0.22 (95%CI [0.02, 2.37], p = 0.214), respectively, for primary and recurrent pterygium. For unacceptable appearance, the pooled HR estimate was 0.33 (95% CI [0.16, 0.66], p = 0.002). There were no statistically significant differences in adverse events (odds ratio (OR) = 0.96, 95% CI [0.46, 1.97], p = 0.901). Conclusions: Available trials indicate that CAT has lower recurrence risk compared to AMT for primary pterygium treatment, as well as lower risk of unacceptable appearance risk. [ABSTRACT FROM AUTHOR]