Xin Liu

BACKGROUND: Increasing data suggest that subclinical hypothyroidism (SCH) and thyroid autoimmunity (TAI) are associated with adverse pregnancy outcomes, but there are limited data on the association of these conditions in early pregnancy with subsequent miscarriage. METHODS: In this prospective cohort study, we screened 3315 women at low risk for thyroid dysfunction at four to eight weeks' gestation from iodine-sufficient areas of China between January 2012 and September 2012. Thyrotropin (TSH), free thyroxine (fT4), and the autoantibodies thyroid-peroxidase antibody (TPOAb) and thyroglobulin antibody (TgAb) were measured. Based on these results, women were divided into four groups for comparison: euthyroidism (ET), isolated SCH, isolated TAI (positive TPOAb or/and TgAb), and SCH with TAI (SCH+TAI). The SCH group was stratified into two subgroups (SCH 1 and SCH 2) on the basis of the level of TSH (2.5 ≤ TSH < 5.22 or 5.22 ≤ TSH < 10 respectively). Accordingly, the SCH+TAI group was also stratified into two subgroups (SCH+TAI 1 and SCH+TAI 2). The outcome of interest was miscarriage, defined as spontaneous pregnancy loss prior to 20 weeks. RESULTS: Compared to women with ET, the risk of miscarriage was significantly higher among women with SCH 2 (7.1% vs. 2.2%, aOR 3.40 [CI 1.62-7.15]; p = 0.002), isolated TAI (5.7% vs. 2.2%, aOR 2.71 [CI 1.43-5.12]; p = 0.003), SCH+TAI 1 (10.0% vs. 2.2%, aOR 4.96 [CI 2.76-8.90]; p = 0.000), and SCH+TAI 2 (15.2% vs. 2.2%, aOR 9.56 [CI 3.76-24.28]; p = 0.000). The gestational ages of 110 women at miscarriage were lower among women with subclinical thyroid abnormalities compared to ET (11.13 ± 3.21 weeks with subclinical thyroid abnormalities vs. 9.33 ± 1.71 weeks with ET; p = 0.024). In parallel with the higher TSH levels, there were earlier gestation ages at miscarriage between subgroups of SCH and SCH+TAI (SCH 1 vs. SCH 2: 10.79 ± 1.77 vs. 9.70 ± 1.47 weeks, p = 0.039; SCH+TAI 1 vs. SCH+TAI 2: 9.59 ± 1.97 vs. 8.88 ± 1.24 weeks, p = 0.031). CONCLUSIONS: Women with SCH and TAI are at an increased risk of miscarriage between four and eight gestational weeks. Women with a combination of SCH and TAI were found to have the highest risk and earlier gestational ages of miscarriage.

The associations between visceral adiposity index (VAI), body shape index and diabetes in adults were inconsistent. We assessed the predictive capacity of VAI and body shape index for diabetes by comparing them with body mass index (BMI) and waist circumference (WC). We used the data of 5838 Chinese men and women aged ≥18 years from the 2009 China Health and Nutrition Survey. Multivariate logistic regression analysis was performed to examine the independent associations between Chinese VAI (CVAI) or body shape index and diabetes. The predictive power of the two indices was assessed using the receiver-operating characteristic (ROC) curve analysis, and compared with those of BMI and WC. Both CVAI and body shape index were positively associated with diabetes. The odds ratios for diabetes were 4.9 (2.9-8.1) and 1.8 (1.2-2.8) in men, and 14.2 (5.3-38.2) and 2.0 (1.3-3.1) in women for the highest quartile of CVAI and body shape index, respectively. The area under the ROC (AUC) and Youden index for CVAI was the highest among all four obesity indicators, whereas BMI and WC are better indicators for diabetes screening. Higher CVAI and body shape index scores are independently associated with diabetes risk. CVAI has a higher overall diabetes diagnostic ability than BMI, WC and body shape index in Chinese adults. BMI and WC, however, are more appealing as screening indicators considering their easy use.

UNLABELLED: Little observational data exist describing telbivudine (LdT) or lamivudine (LAM) use in late pregnancy for preventing hepatitis B mother-to-child transmission (MTCT) in real-world settings. During the period of January 2009 to March 2011, we enrolled hepatitis B e antigen-positive mothers with HBV DNA >6 log10 copies/mL in China. At gestation week 28, the mothers received LdT or LAM until postpartum week 4 or no treatment (NTx). The study endpoints were the safety of LdT/LAM use and MTCT rates. Of the 700 mothers enrolled, 648 (LdT/LAM/NTx=252/51/345) completed the 52-week study with 661 infants (LdT/LAM/NTx=257/52/352). On treatment, viral rebound occurred in 1.6% of mothers, all resulting from medication noncompliance. There was no genotypic mutation detected. At delivery, significantly lower HBV DNA levels were noted in mothers who received LdT or LAM versus NTx. Alanine aminotransferase flares were observed in 17.1% of treated mothers versus 6.3% of untreated mothers (P < 0.001). At birth, hepatitis B surface antigen (HBsAg) was detected in 20% and 24% of newborns in the treated and NTx groups, respectively. At week 52, an intention-to-treat analysis indicated 2.2% (95% confidence [CI]: 0.6-3.8) of HBsAg+ infants from the treated group versus 7.6% (95% CI: 4.9-10.3) in the NTx group (P50.001) and no difference of HBsAg+ rate between infants in the LdT and LAM groups(1.9% vs. 3.7%; P=0.758). On-treatment analysis indicated 0% of HBsAg+ infants in the treated group versus 2.84% in the NTx group (P=0.002). There were no differences for gestational age or infants' height, weight, Apgar scores, or birth defect rates between infants from the treated and untreated groups. CONCLUSIONS: LdT and LAM use in late pregnancy for highly viremic mothers was equally effective in reducing MTCT. The treatment was well tolerated with no safety concerns identified.

Dietary fibers/probiotics may relieve constipation via optimizing gut microbiome, yet with limited trial-based evidences. We aimed to evaluate the effects of formulas with dietary fibers or probiotics on functional constipation symptoms, and to identify modulations of gut microbiota of relevance. We conducted a 4-week double-blinded randomized placebo-controlled trial in 250 adults with functional constipation. Intervention: A: polydextrose; B: psyllium husk; C: wheat bran + psyllium husk; D: Bifidobacterium animalis subsp. lactis HN019 + Lacticaseibacillus rhamnosus HN001; Placebo: maltodextrin. Oligosaccharides were also included in group A to D. 16S rRNA sequencing was used to assess the gut microbiota at weeks 0, 2, and 4. A total of 242 participants completed the study. No time-by-group effect was observed for bowel movement frequency (BMF), Bristol stool scale score (BSS), and degree of defecation straining (DDS), while BSS showed mean increases of 0.95–1.05 in group A to D (all P < 0.05), but not significantly changed in placebo (P = 0.170), and 4-week change of BSS showed similarly superior effects of the interventions as compared placebo. Group D showed a marginal reduction in plasma 5-hydroxytryptamine. Group A resulted in a higher Bifidobacterium abundance than placebo at week 2 and 4. Fourteen genera showed intervention-specific increasing or decreasing trends continuously, among which Anaerostipes showed increasing trends in groups B and C, associated with BMF increase. Random forest models identified specific baseline microbial genera panels predicting intervention responders. In conclusion, we found that the dietary fibers or probiotics may relieve hard stool, with intervention-specific changes in gut microbiota relevant to constipation relief. Baseline gut microbiota may predispose the intervention responsiveness. ClincialTrials.gov number, NCT04667884.

BACKGROUNDCurrent clinical management of patients with pulmonary nodules involves either repeated low-dose CT (LDCT)/CT scans or invasive procedures, yet causes significant patient misclassification. An accurate noninvasive test is needed to identify malignant nodules and reduce unnecessary invasive tests.METHODWe developed a diagnostic model based on targeted DNA methylation sequencing of 389 pulmonary nodule patients' plasma samples and then validation in 140 plasma samples independently. We tested the model in different stages and subtypes of pulmonary nodules.RESULTSA 100-feature model was developed and validated for pulmonary nodule diagnosis; the model achieved a receiver operating characteristic curve-AUC (ROC-AUC) of 0.843 on 140 independent validation samples, with an accuracy of 0.800. The performance was well maintained in (a) a 6 to 20 mm size subgroup (n = 100), with a sensitivity of 1.000 and adjusted negative predictive value (NPV) of 1.000 at 10% prevalence; (b) stage I malignancy (n = 90), with a sensitivity of 0.971; (c) different nodule types: solid nodules (n = 78) with a sensitivity of 1.000 and adjusted NPV of 1.000, part-solid nodules (n = 75) with a sensitivity of 0.947 and adjusted NPV of 0.983, and ground-glass nodules (n = 67) with a sensitivity of 0.964 and adjusted NPV of 0.989 at 10% prevalence. This methylation test, called PulmoSeek, outperformed PET-CT and 2 clinical prediction models (Mayo Clinic and Veterans Affairs) in discriminating malignant pulmonary nodules from benign ones.CONCLUSIONThis study suggests that the blood-based DNA methylation model may provide a better test for classifying pulmonary nodules, which could help facilitate the accurate diagnosis of early stage lung cancer from pulmonary nodule patients and guide clinical decisions.FUNDINGThe National Key Research and Development Program of China; Science and Technology Planning Project of Guangdong Province; The National Natural Science Foundation of China National.