The preterm-born adult population is ever increasing following improved survival rates of premature births. We conducted a meta-analysis to investigate long-term effects of preterm birth on renal ...function in preterm-born survivors. We searched PubMed and EMBASE to identify studies that compared renal function in preterm-born survivors and full-term-born controls, published until 2 February 2019. A random effects model with standardized mean difference (SMD) was used for meta-analyses. Heterogeneity of the studies was evaluated using Higgin's
statistics. Risk of bias was assessed using the Newcastle-Ottawa quality assessment scale. Of a total of 24,388 articles screened, 27 articles were finally included. Compared to full-term-born controls, glomerular filtration rate and effective renal plasma flow were significantly decreased in preterm survivors (SMD -0.54, 95% confidence interval (CI), -0.85 to -0.22,
= 0.0008; SMD -0.39, 95% CI, -0.74 to -0.04,
= 0.03, respectively). Length and volume of the kidneys were significantly decreased in the preterm group compared to the full-term controls (SMD -0.73, 95% CI, -1.04 to -0.41,
< 0.001; SMD -0.82, 95% CI, -1.05 to -0.60,
< 0.001, respectively). However, serum levels of blood urea nitrogen, creatinine, and cystatin C showed no significant difference. The urine microalbumin to creatinine ratio was significantly increased in the preterm group. Both systolic and diastolic blood pressures were also significantly elevated in the preterm group, although the plasma renin level did not differ. This meta-analysis demonstrates that preterm-born survivors may be subject to decreased glomerular filtration, increased albuminuria, decreased kidney size and volume, and hypertension even though their laboratory results may not yet deteriorate.
∙ Neonatal sepsis is a global problem and significant cause of neonatal mortality and adverse short- and long-term outcomes. ∙ Due to severe limitations diagnosing neonatal sepsis, there is a ...critical need to identify reliable specific biomarkers for early detection. ∙ nCD11b might be an accurate and rapid biomarker for the early detection of neonatal sepsis.
This study used machine learning and a national prospective cohort registry database to analyze the major risk factors of necrotizing enterocolitis (NEC) in very low birth weight (VLBW) infants, ...including environmental factors. The data consisted of 10,353 VLBW infants from the Korean Neonatal Network database from January 2013 to December 2017. The dependent variable was NEC. Seventy-four predictors, including ambient temperature and particulate matter, were included. An artificial neural network, decision tree, logistic regression, naïve Bayes, random forest, and support vector machine were used to evaluate the major predictors of NEC. Among the six prediction models, logistic regression and random forest had the best performance (accuracy: 0.93 and 0.93, area under the receiver-operating-characteristic curve: 0.73 and 0.72, respectively). According to random forest variable importance, major predictors of NEC were birth weight, birth weight Z-score, maternal age, gestational age, average birth year temperature, birth year, minimum birth year temperature, maximum birth year temperature, sepsis, and male sex. To the best of our knowledge, the performance of random forest in this study was among the highest in this line of research. NEC is strongly associated with ambient birth year temperature, as well as maternal and neonatal predictors.
Abstract
This study aimed to analyze major predictors of adverse birth outcomes in very low birth weight (VLBW) infants including particulate matter concentration (PM
10
), using machine learning and ...the national prospective cohort. Data consisted of 10,423 VLBW infants from the Korean Neonatal Network database during January 2013–December 2017. Five adverse birth outcomes were considered as the dependent variables, i.e., gestational age less than 28 weeks, gestational age less than 26 weeks, birth weight less than 1000 g, birth weight less than 750 g and small-for-gestational age. Thirty-three predictors were included and the artificial neural network, the decision tree, the logistic regression, the Naïve Bayes, the random forest and the support vector machine were used for predicting the dependent variables. Among the six prediction models, the random forest had the best performance (accuracy 0.79, area under the receiver-operating-characteristic curve 0.72). According to the random forest variable importance, major predictors of adverse birth outcomes were maternal age (0.2131), birth-month (0.0767), PM
10
month (0.0656), sex (0.0428), number of fetuses (0.0424), primipara (0.0395), maternal education (0.0352), pregnancy-induced hypertension (0.0347), chorioamnionitis (0.0336) and antenatal steroid (0.0318). In conclusion, adverse birth outcomes had strong associations with PM
10
month as well as maternal and fetal factors.
Abstract Neurodevelopmental disorders (NDD) in offspring are associated with a complex combination of pre-and postnatal factors. This study uses machine learning and population data to evaluate the ...association between prepregnancy or perinatal risk factors and the NDD of offspring. Population-based retrospective cohort data were obtained from Korea National Health Insurance Service claims data for 209,424 singleton offspring and their mothers who gave birth for the first time in 2007. The dependent variables were motor development disorder (MDD), cognitive development disorder (CDD) and combined overall neurodevelopmental disorder (NDD) from offspring. Seventeen independent variables from 2002 to 2007 were included. Random forest variable importance and Shapley Additive Explanation (SHAP) values were calculated to analyze the directions of its associations with the predictors. The random forest with oversampling registered much higher areas under the receiver-operating-characteristic curves than the logistic regression of interaction and non-linearity terms, 79% versus 50% (MDD), 82% versus 52% (CDD) and 74% versus 50% (NDD). Based on random forest variable importance, low socioeconomic status and age at birth were highly ranked. In SHAP values, there was a positive association between NDD and pre- or perinatal outcomes, especially, fetal male sex with growth restriction associated the development of NDD in offspring.
It is well known that periodontitis, diagnosed mainly by periodontal probing, is associated with adverse pregnancy outcomes. However, periodontal probing is time-consuming, highly discomforting, ...inaccurate, and invasive. We aimed to assess whether periodontitis severity based on radiological staging in accordance with the 2017 new consensus classification was related to adverse pregnancy and neonatal outcomes. The medical records of 165 mothers who underwent panoramic radiography within 5 years before and after the time of delivery and of their singleton neonates were retrospectively reviewed. Twenty-two mothers (13.3%) had severe periodontitis (SP), and 143 (86.7%) had mild or moderate periodontitis (MP). In relation to adverse pregnancy outcomes, uterine leiomyoma (18.2% vs. 4.2%, P = 0.029), chronic hypertension (9.1% vs. 0.7%, P = 0.047), and preeclampsia (13.6% vs. 2.1%, P = 0.032) occurred significantly more frequently in the SP group than in the MP group. The incidences of very preterm birth (13.6% vs. 1.4%, P = 0.017), extremely preterm birth (9.1% vs. 0.7%, P = 0.047), and small for gestational age (22.7% vs. 5.6%, P = 0.017) were also significantly higher in the SP group than in the MP group. Radiological screening of maternal periodontitis could be useful for predicting adverse pregnancy and neonatal outcomes as well as diagnosing SP in pregnant women.
The prognostic potential of PD-L1 is currently unclear in gastric carcinomas, although the immune checkpoint PD-1/PD-L1 inhibitors have produced promising results in clinical trials.
We explored the ...prognostic implications of programmed death ligand 1 (PD-L1) in 514 consecutive surgically-resected gastric carcinomas. Overall survival and recurrence-free survival were evaluated. Immunohistochemistry for PD-L1, CD8, FOXP3, and PD-1, and molecular grouping by in situ hybridization for Epstein-Barr virus (EBV)-encoded small RNAs and multiplex PCR for microsatellite instability (MSI) markers were performed. Additionally, to explore the function inherent to PD-L1, PD-L1-specific siRNA transfection, cell proliferation, invasion, migration and apoptosis assays were conducted in five gastric carcinoma cell lines.
PD-L1(+) tumor and immune cells were observed in 101 (20%) and 244 patients (47%), respectively. "Tumoral PD-L1(+)/immune cell PD-L1(-)/CD8
tumor-infiltrating lymphocytes (TILs)," and more advanced-stage tumors were associated with unfavorable clinical outcomes in the entire cohort through multivariate analysis. Furthermore, tumoral PD-L1(+)/FOXP3
TILs were associated with worse clinical outcomes in EBV-positive and MSI-high carcinomas. Tumoral PD-L1(+) alone was an adverse prognostic factor in EBV-positive carcinomas, but not in MSI-high carcinomas, whereas PD-L1(+) immune cells or FOXP3
TILs alone were correlated with a favorable prognosis. PD-L1 knockdown in gastric carcinoma cells suppressed cell proliferation, invasion and migration, and increased apoptosis, which were all statistically significant in two EBV(+) cell lines, but not all in three EBV(-) cell lines.
The prognostic impact of PD-L1 may depend on the tumor microenvironment, and statuses of EBV and MSI, although PD-L1 innately promotes cancer cell survival in cell-based assays. The combination of "tumoral PD-L1/immune cell PD-L1/CD8
TILs" may serve as an independent prognostic factor. Tumoral PD-L1(+)/immune cell PD-L1(-)/CD8
TILs showing a worse prognosis may be beneficial for combinatorial therapies of anti-PD-L1/PD-1 and anti-cytotoxic T-lymphocyte associated antigen 4 (CTLA4) that would promote effector T cells, thus attack the tumor.
Increased survival in the very preterm population results in a higher risk of developing neurodevelopmental and behavioral disabilities among survivors. We examined the outcomes of very preterm ...infants and parents after a preventive intervention program of four home visits by a specialized nurse, 5 days, 2 weeks, and 1 month after discharge, respectively, and at CA 2 months, followed by up to 12 times of group sessions between CA 3 and 6 months. Our multicenter randomized controlled trial assessed 138 preterm infants (gestational age ≤30 weeks or birth weight ≤1500 g) enrolled from the three participating hospitals. We randomly allocated the preterm babies to either the intervention or the control group. The primary outcome was the neurodevelopmental outcomes of Bayley-III scores at CA 10 and 24 months. At CA 10 months and 24 months, there were no significant differences between the intervention and control groups in the cognitive, motor, and language domains of Bayley-III scores. In addition, there were no significant differences in the mother's depression scale, mother-child attachment, and the modified Infant and Toddler Social and Emotional Assessment.
Background
The host immune response (HIR) against tumor cells is one of the key players in antitumor activities. However, the relationship between HIR and regional lymph nodes (LN) and their impacts ...on prognosis have not been studied.
Methods
This study analyzed HIR and clinicopathologic factors for 8819 consecutive gastric cancer patients who underwent gastrectomy and D2 LN dissection. The findings confirmed Epstein–Barr virus (EBV) with Epstein–Barr encoding region in situ hybridization, HIR grading (G1, G2, and G3), LN numbers classified into seven groups, and performed ordinal regression analysis.
Results
The mean number of LNs was 41. A higher degree of HIR was significantly associated with male sex, EBV+, non-intestinal histology by Lauren classification, earlier American Joint Committee on Cancer (AJCC) stage, and greater number of LNs (
P
< 0.001). Female gender, younger age (< 60 years), EBV+, non-intestinal histology, higher HIR grade (G2 and G3), larger tumor size, and deeper invasion depth were significantly related to a higher number of LNs, with an odds ratio greater than 1. In cancer-specific survival analyses, EBV+, younger age, higher HIR grade (G3), and increased number of LNs were independent prognostic factors in addition to AJCC stage.
Conclusions
The HIR was associated with increased number of LNs was a significant favorable prognosticator.
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