Maternal Exposure to Pesticides and Risk of Autism Spectrum Disorders in Offspring: A Meta-analysis.

This meta-analysis was conducted to estimate the overall association between maternal exposure to pesticides and risk of ASD in offspring. PubMed, EMBASE, Web of Science, and the PsycINFO were searched until December 30, 2020 to include eligible studies. Eight studies with 50,426 participants, 5810 of whom had ASD, were involved in the study. Overall, the summary OR (95% confidence interval) of ASDs in offspring for maternal exposure to pesticide estimated by residential proximity measures and self-report was 1.88 (1.10-3.20). However, maternal exposure to pesticide measured by biomarkers was not associated with an increased risk of ASDs (pooled OR 1.13; 95% CI 0.83-1.54). Further well-designed studies are needed to confirm our findings.

Efficacy and Safety of Leflunomide for Refractory COVID-19: A Pilot Study.

Background: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may persist in patients with coronavirus disease 2019 (COVID-19) despite receiving standard care. Methods: In this pilot study of hospitalized adult patients (≥18 years of age), with radiologically confirmed pneumonia who were SARS-CoV-2 positive for more than 28 days despite standard care, were assigned to receive standard of care (SOC, grp I) or leflunomide + SOC (grp 2). After 2 weeks, grp 1 and grp 2 patients who continued to be SARS-CoV-2-positive received leflunomide for 14 days while continuing SOC. The primary outcomes were the rate of and time to SARS-CoV-2 clearance and the 14-day and 30-day hospital discharge rate. Results: 12 patients were enrolled in grp 1 and 15 patients were in grp 2. The 14 days SARS-CoV-2 viral clearance rate was 80.0% (12/15) for grp 2 patients receiving leflunomide vs. 16.7% for grp 1 patients (2/12) (p = 0.002). By day 14, the median time to SARS-CoV-2 clearance was 6.0 days (range 1-12, IQR 1-12) for grp 2 patients. In grp 1, two patients converted to viral negative on days 1 and 6 (p = 0.002). The 14-day discharge rate was 73.3% (11/15) for the grp 2 vs. 8.3% (1/12) for grp 1 (p = 0.001). The 30 days discharge rate was 100% (15/15) for the grp 2 vs. 66.7% (8/12) for grp 1. No severe adverse events or deaths were reported. Conclusion: Leflunomide may improve the SARS-CoV-2 clearance rate and discharge rate in patients with refractory COVID-19. The tolerability of the 14-28 days course of treatment with leflunomide is acceptable. These preliminary observations need to be verified by a large sample size and randomized controlled trial.

Clinical characteristics and manifestations in older patients with COVID-19.

BACKGROUND: To investigate the clinical characteristics and manifestations of older patients with coronavirus disease 2019 (COVID-19). METHODS: In this retrospective study, 566 patients with confirmed COVID-19 were enrolled and the clinical characteristics, laboratory findings, complications and outcome data were collected and analyzed. RESULTS: Among the 566 patients (median age, 61.5 years) with COVID-19, 267 (47.2%) patients were male and 307 (54.2%) were elderly. Compared with younger patients, older patients had more underlying comorbidities and laboratory abnormalities. A higher rate of acute respiratory distress syndrome (ARDS), acute cardiac injury and heart failure was observed in the older group as compared with younger and middle-aged groups, particularly those oldest-old patients had more multi-organ damage. Older patients with COVID-19 were more likely to suffer from acute cardiac injury in cases with preexistenting cardiovascular diseases, while there was no difference among the three groups when patients had no history of cardiovascular diseases. Older patients presented more severe with the mortality of 18.6%, which was higher than that in younger and middle-aged patients (P < 0.05). Multivariable analysis showed that age, lymphopenia, ARDS, acute cardiac injury, heart failure and skeletal muscle injury were associated with death in older patients, while glucocorticoids might be harmful. CONCLUSIONS: Older patients, especially the oldest-old patients were more likely to exhibit significant systemic inflammation, pulmonary and extrapulmonary organ damage and a higher mortality. Advanced age, lymphopenia, ARDS, acute cardiac injury, heart failure and skeletal muscle injury were independent predictors of death in older patients with COVID-19 and glucocorticoids should be carefully administered in older patients.

The characteristics and outcomes of 681 severe cases with COVID-19 in China.

PURPOSE: To clarify the epidemiological, clinical, and therapeutic features of patients with severe COVID-19. METHODS: In this study, we enrolled 681 patients with confirmed cases of severe COVID-19. The epidemiological, demographic, clinical, laboratory, treatment, and outcome data were collected. RESULTS: The median age of the study participants was 65 years, 53.2% were male, and 104 (15.3%) died. Age, Neutrophil-To-Lymphocyte Ratio (NLR), acute myocardial injury, and levels of C-reactive protein (CRP), lactate dehydrogenase (LDH), and CD3 T cells counts were independently associated with death, while arbidol and ribavirin were protective from death. The combination of NLR and acute myocardial injury on admission (AUC = 0.914) predicted mortality better than NLR, CRP, LDH, and acute myocardial injury. There were 312 (45.8%) patients with cardiovascular disease, of whom 23.4% died. ß-blockers, ACEI/ARB, arbidol, and ribavirin might have a beneficial effect for severe COVID-19 patients with cardiovascular disease. CONCLUSION: The combination of NLR and acute myocardial injury on admission was highly predictive of mortality and survival. Clinicians should adopt more aggressive strategies for patients with a high NLR (>6.66) combined with myocardial injury. ß-blockers and ACEI/ARB, as well as arbidol and ribavirin, were effective in COVID-19 patients with cardiovascular disease.

Subchronic olanzapine treatment decreases the expression of pancreatic glucose transporter 2 in rat pancreatic ß cells.

BACKGROUND: Olanzapine is a second generation antipsychotic. A common side effect in humans is weight gain, but the mechanisms are mostly unknown. AIM: To study the effects of subchronic olanzapine treatment on body weight, fasting plasma glucose (FPG), fasting insulin (FINS), C-peptide, insulin sensitivity index (ISI), and expression of glucose transporter 2 (GLUT2) in rat pancreatic ß cells. MATERIALS AND METHODS: Female Sprague-Dawley rats were randomly divided into two groups: the olanzapine-treated group and the control group (each n = 8). Rats in the olanzapine-treated group intragastrically received olanzapine 5 mg/kg/day for 28 days; the rats in the control group received the same volume of vehicle. FPG and body weight were measured on the 1st, 7th, 14th and 28th day. FINS and C-peptide were measured using immunoradiometric assays at baseline and on the 28th day. GLUT2 mRNA and protein expressions in pancreatic ß cells were analyzed by RT-PCR and western blot. RESULTS: Olanzapine-treated rats had higher body weight (227.4 ± 8.9 vs. 211.0 ± 9.9 g), FPG (5.86 ± 0.42 vs. 4.24 ± 0.29 mmol/L), FINS (17.34 ± 3.64 vs. 10.20 ± 1.50 µIU/mL), and C-peptide (0.154 ± 0.027 vs. 0.096 ± 0.009 ng/mL) than those in controls (all P < 0.05) at the 28th day. Pancreatic ß cells of the olanzapine-treated group showed lower ISI (-4.60 ± 0.23 vs. -3.76 ± 0.20) and GLUT2 levels (mRNA: 1.12 ± 0.02 vs. 2.00 ± 0.03; protein: 0.884 ± 0.134 vs. 1.118 ± 0.221) than those in controls (all P < 0.05). CONCLUSIONS: Subchronic olanzapine treatment inhibited expression of GLUT2 in rat pancreatic ß cells. Therefore, it may disturb glucose metabolism via the insulin resistance of ß cells, but confirmation in humans is needed.