Safety and Effectiveness of COVID-19 Vaccines During Pregnancy: A Living Systematic Review and Meta-analysis.

BACKGROUND: Pregnant persons are susceptible to significant complications following COVID-19, even death. However, worldwide COVID-19 vaccination coverage during pregnancy remains suboptimal. OBJECTIVE: This study assessed the safety and effectiveness of COVID-19 vaccines administered to pregnant persons and shared this evidence via an interactive online website. METHODS: We followed Cochrane methods to conduct this living systematic review. We included studies assessing the effects of COVID-19 vaccines in pregnant persons. We conducted searches every other week for studies until October 2023, without restrictions on language or publication status, in ten databases, guidelines, preprint servers, and COVID-19 websites. The reference lists of eligible studies were hand searched to identify additional relevant studies. Pairs of review authors independently selected eligible studies using the web-based software COVIDENCE. Data extraction and risk of bias assessment were performed independently by pairs of authors. Disagreements were resolved by consensus. We performed random-effects meta-analyses of adjusted relative effects for relevant confounders of comparative studies and proportional meta-analyses to summarize frequencies from one-sample studies using R statistical software. We present the GRADE certainty of evidence from comparative studies. Findings are available on an interactive living systematic review webpage, including an updated evidence map and real-time meta-analyses customizable by subgroups and filters. RESULTS: We included 177 studies involving 638,791 participants from 41 countries. Among the 11 types of COVID-19 vaccines identified, the most frequently used platforms were mRNA (154 studies), viral vector (51), and inactivated virus vaccines (17). Low to very low-certainty evidence suggests that vaccination may result in minimal to no important differences compared to no vaccination in all assessed maternal and infant safety outcomes from 26 fewer to 17 more events per 1000 pregnant persons, and 13 fewer to 9 more events per 1000 neonates, respectively. We found statistically significant reductions in emergency cesarean deliveries (9%) with mRNA vaccines, and in stillbirth (75-83%) with mRNA/viral vector vaccines. Low to very low-certainty evidence suggests that vaccination during pregnancy with mRNA vaccines may reduce severe cases or hospitalizations in pregnant persons with COVID-19 (72%; 95% confidence interval [CI] 42-86), symptomatic COVID-19 (78%; 95% CI 21-94), and virologically confirmed SARS-CoV-2 infection (82%; 95% CI 39-95). Reductions were lower with other vaccine types and during Omicron variant dominance than Alpha and Delta dominance. Infants also presented with fewer severe cases or hospitalizations due to COVID-19 and laboratory-confirmed SARS-CoV-2 infection (64%; 95% CI 37-80 and 66%; 95% CI 37-81, respectively). CONCLUSIONS: We found a large body of evidence supporting the safety and effectiveness of COVID-19 vaccines during pregnancy. While the certainty of evidence is not high, it stands as the most reliable option available, given the current absence of pregnant individuals in clinical trials. Results are shared in near real time in an accessible and interactive format for scientists, decision makers, clinicians, and the general public. This living systematic review highlights the relevance of continuous vaccine safety and effectiveness monitoring, particularly in at-risk populations for COVID-19 impact such as pregnant persons, during the introduction of new vaccines. CLINICAL TRIAL REGISTRATION: PROSPERO: CRD42021281290.

Mechanoresponsive Protein Crystals for NADH Recycling in Multicycle Enzyme Reactions.

NAD(H)-dependent enzymes play a crucial role in the biosynthesis of pharmaceuticals and fine chemicals, but the limited recyclability of the NAD(H) cofactor hinders its more general application. Here, we report the generation of mechano-responsive PEI-modified Cry3Aa protein crystals and their use for NADH recycling over multiple reaction cycles. For demonstration of its practical utility, a complementary Cry3Aa protein particle containing genetically encoded and co-immobilized formate dehydrogenase for NADH regeneration and leucine dehydrogenase for catalyzing the NADH-dependent l-tert-leucine (l-tert-Leu) biosynthesis has been produced. When combined with the PEI-modified Cry3Aa crystal, the resultant reaction system could be used for the efficient biosynthesis of l-tert-Leu for up to 21 days with a 10.5-fold improvement in the NADH turnover number.

A Prediction Nomogram for Fractured Vertebra Recollapse After Posterior Reduction and Pedicle Screw Fixation in Thoracolumbar Fractures.

OBJECTIVE: This study aimed to establish a predictive nomogram model for recollapse of fractured vertebra after posterior pedicle screw fixation in thoracolumbar fractures (TLFs). METHODS: Patients undergoing posterior pedicle screw fixation for TLFs at our hospital between January 2016 and December 2021 were retrospectively reviewed. Patients were divided into 2 groups according to the presence or absence of recollapse of the fractured vertebra at the final follow-up. The predictors for fractured vertebra recollapse were identified by univariate and multivariable logistic regression analysis, and a nomogram model was developed. The prediction performance and internal validation were established. RESULTS: A total of 224 patients were included in this study. Of these, 46 (20.5%) patients developed recollapse of fractured vertebra. Age, thoracic and lumbar injury severity score, screw distribution in the fractured vertebra, and anterior vertebral height compression ratio were associated with vertebral recollapse. These predictors were used to construct a predictive nomogram. The area under the receiver operating characteristic curve of the nomogram model was 0.891. The concordance index was 0.891, and it was 0.877 with bootstrapping validation. The calibration curves and decision curve analysis also suggested that the nomogram model had excellent predictive performances for fractured vertebra recollapse. CONCLUSIONS: A clinical nomogram incorporating 4 variables was constructed to predict fractured vertebra recollapse after posterior pedicle screw fixation for TLFs. The nomogram demonstrated good calibration and discriminative abilities, which may help clinicians to make better treatment decisions.

ExtraCorporeal Membrane Oxygenation in the therapy for REfractory Septic shock with Cardiac function Under Estimated (ECMO-RESCUE): study protocol for a prospective, multicentre, non-randomised cohort study.

INTRODUCTION: Severe septic cardiomyopathy (SCM) is one of the main causes of refractory septic shock (RSS), with a high mortality. The application of venoarterial extracorporeal membrane oxygenation (ECMO) to support the impaired cardiac function in patients with septic shock remains controversial. Moreover, no prospective studies have been taken to address whether venoarterial ECMO treatment could improve the outcome of patients with sepsis-induced cardiogenic shock. The objective of this study is to assess whether venoarterial ECMO treatment can improve the 30-day survival rate of patients with sepsis-induced refractory cardiogenic shock. METHODS AND ANALYSIS: ExtraCorporeal Membrane Oxygenation in the therapy for REfractory Septic shock with Cardiac function Under Estimated is a prospective, multicentre, non-randomised, cohort study on the application of ECMO in SCM. At least 64 patients with SCM and RSS will be enrolled in an estimated ratio of 1:1.5. Participants taking venoarterial ECMO during the period of study are referred to as cohort 1, and patients receiving only conventional therapy without ECMO belong to cohort 2. The primary outcome is survival in a 30-day follow-up period. Other end points include survival to intensive care unit (ICU) discharge, hospital survival, 6-month survival, quality of life for long-term survival (EQ-5D score), successful rate of ECMO weaning, long-term survivors' cardiac function, the number of days alive without continuous renal replacement therapy, mechanical ventilation and vasopressor, ICU and hospital length of stay, the rate of complications potentially related to ECMO treatment. ETHICS AND DISSEMINATION: The trial has been approved by the Clinical Research and Application Institutional Review Board of the Second Affiliated Hospital of Guangzhou Medical University (2020-hs-51). Participants will be screened and enrolled from ICU patients with septic shock by clinicians, with no public advertisement for recruitment. Results will be disseminated in research journals and through conference presentations. TRIAL REGISTRATION NUMBER: NCT05184296.

Phthalate exposure and subfecundity in preconception couples: A nested case-control study.

BACKGROUND: Phthalates (PAEs) are endocrine-disrupting chemicals ubiquitously found in the environment. This study aimed to examine the association between exposure of PAEs and subfecundity in preconception couples. METHODS: This is a nested case-control study based on preconception cohort. Preconception couples with intention to conceive were enrolled and followed up until a clinically confirmed pregnancy or 12 menstrual cycles of preparation for conception. A total of 107 couples with subfecundity- time to pregnancy (TTP) more than 12 menstrual cycles, and 144 couples ≤12 cycles were included in the analysis. The levels of PAE metabolites in one spot urine samples were detected and compared between the groups. The weighted quantile sum (WQS) regression model and Bayesian kernel machine regression (BKMR) model were used to examine the joint effects of couples' exposure to PAEs on subfecundity. RESULTS: Using the multivariate binary logistic regression model, compared to the lowest quartile of urinary ∑PAEs concentration group, both preconception females (aOR=2.42, 95% CI: 1.10-5.30, p=0.027) and males (aOR=2.99, 95% CI: 1.36-6.58, p=0.006) in the highest quartile group had an increased risk of subfecundity, and a dose-response relationship was observed between PAEs and the risk of subfecundity. The WQS analyses found that co-exposure to PAE mixture was a risk factor for subfecundity in preconception female (aOR=1.76, 95% CI: 1.38-2.26, p<0.001), male (aOR=1.58, 95% CI: 1.20-2.08, p=0.001), and couple (aOR=2.39, 95% CI: 1.61-3.52, p<0.001). The BKMR model found a positive combined effect of mixed exposure to PAEs on the risk of subfecundity. CONCLUSIONS: PAEs increase the risk of subfecundity in preconception couples. Our research reinforced the need of monitoring PAE exposure for the purpose of improving human reproductive health.

Non-target screening and prioritization of organic contaminants in seawater desalination and their ecological risk assessment.

The impact of desalination brine on the marine environment is a global concern. Regarding this, salinity is generally accepted as the major environmental factor in desalination concentrate. However, recent studies have shown that the influence of organic contaminants in brine cannot be ignored. Therefore, a non-targeted screening method based on comprehensive two-dimensional gas chromatography-quadrupole mass spectrometry (GC × GC-qMS) was developed for identifying organic contaminants in the desalination brine. A total of 404 compounds were tentatively identified from four seawater desalination plants (three reverse osmosis plants and one multiple effect distillation plant) in China. The identified compounds were prioritized based on their persistence, bioaccumulation, ecotoxicity, usage, and detection frequency. Twenty-one (21) compounds (seven phthalates, ten pesticides, four trihalomethanes) were then selected for further quantitative analysis and ecological risk assessment, including compounds from the priority list along with substances from the same chemical classes. Ecologically risky substances in brine include diisobutylphthalate and bis(2-Ethylhexyl) phthalate, atrazine and acetochlor, and bromoform. Most of the contaminants come from raw seawater, and no high risk contaminants introduced by the desalination process have been found except for disinfection by-products. In brine discharge management, people believed that all pollution in raw seawater was concentrated by desalination process. This study shows that not all pollutants are concentrated during the desalination process. In this study, the total concentration of pesticide in the brine increased by 58.42%. The concentration of ∑PAEs decreased by 13.65% in reverse osmosis desalination plants and increased by 10.96% in the multi-effect distillation plant. The concentration of trihalomethane increased significantly in the desalination concentrate. The change in the concentration of pollutants in the desalination concentrate was related to the pretreatment method and the chemical characteristics of the contaminants. The method and results given in this study hinted a new idea to identify and control the environmental impact factors of brine.

Using maternal and neonatal data collection systems for coronavirus disease 2019 (COVID-19) vaccines active safety surveillance in low- and middle-income countries: an international modified Delphi study.

Background: Given that pregnant women are now included among those for receipt coronavirus disease 2019 (COVID-19) vaccines, it is important to ensure that information systems can be used (or available) for active safety surveillance, especially in low- and middle-income countries (LMICs). The aim of this study was to build consensus about the use of existing maternal and neonatal data collection systems in LMICs for COVID-19 vaccines active safety surveillance, a basic set of variables, and the suitability and feasibility of including pregnant women and LMIC research networks in COVID-19 vaccines pre-licensure activities. Methods: A three-stage modified Delphi study was conducted over three months in 2020. An international multidisciplinary panel of 16 experts participated. Ratings distributions and consensus were assessed, and ratings' rationale was analyzed. Results: The panel recommended using maternal and neonatal data collection systems for active safety surveillance in LMICs (median 9; disagreement index [DI] -0.92), but there was no consensus (median 6; DI 1.79) on the feasibility of adapting these systems. A basic set of 14 maternal, neonatal, and vaccination-related variables. Out of 16 experts, 11 supported a basic set of 14 maternal, neonatal, and vaccination-related variables for active safety surveillance. Seven experts agreed on a broader set of 26 variables. The inclusion of pregnant women for COVID-19 vaccines research (median 8; DI -0.61) was found appropriate, although there was uncertainty on its feasibility in terms of decision-makers' acceptability (median 7; DI 10.00) and regulatory requirements (median 6; DI 0.51). There was no consensus (median 6; DI 2.35) on the feasibility of including research networks in LMICs for conducting clinical trials amongst pregnant women. Conclusions: Although there was some uncertainty regarding feasibility, experts recommended using maternal and neonatal data collection systems and agreed on a common set of variables for COVID-19 vaccines active safety surveillance in LMICs.