Clinical risk factors of adverse outcomes among women with COVID-19 in the pregnancy and postpartum period: a sequential, prospective meta-analysis.

OBJECTIVE: This sequential, prospective meta-analysis sought to identify risk factors among pregnant and postpartum women with COVID-19 for adverse outcomes related to disease severity, maternal morbidities, neonatal mortality and morbidity, and adverse birth outcomes. DATA SOURCES: We prospectively invited study investigators to join the sequential, prospective meta-analysis via professional research networks beginning in March 2020. STUDY ELIGIBILITY CRITERIA: Eligible studies included those recruiting at least 25 consecutive cases of COVID-19 in pregnancy within a defined catchment area. METHODS: We included individual patient data from 21 participating studies. Data quality was assessed, and harmonized variables for risk factors and outcomes were constructed. Duplicate cases were removed. Pooled estimates for the absolute and relative risk of adverse outcomes comparing those with and without each risk factor were generated using a 2-stage meta-analysis. RESULTS: We collected data from 33 countries and territories, including 21,977 cases of SARS-CoV-2 infection in pregnancy or postpartum. We found that women with comorbidities (preexisting diabetes mellitus, hypertension, cardiovascular disease) vs those without were at higher risk for COVID-19 severity and adverse pregnancy outcomes (fetal death, preterm birth, low birthweight). Participants with COVID-19 and HIV were 1.74 times (95% confidence interval, 1.12-2.71) more likely to be admitted to the intensive care unit. Pregnant women who were underweight before pregnancy were at higher risk of intensive care unit admission (relative risk, 5.53; 95% confidence interval, 2.27-13.44), ventilation (relative risk, 9.36; 95% confidence interval, 3.87-22.63), and pregnancy-related death (relative risk, 14.10; 95% confidence interval, 2.83-70.36). Prepregnancy obesity was also a risk factor for severe COVID-19 outcomes including intensive care unit admission (relative risk, 1.81; 95% confidence interval, 1.26-2.60), ventilation (relative risk, 2.05; 95% confidence interval, 1.20-3.51), any critical care (relative risk, 1.89; 95% confidence interval, 1.28-2.77), and pneumonia (relative risk, 1.66; 95% confidence interval, 1.18-2.33). Anemic pregnant women with COVID-19 also had increased risk of intensive care unit admission (relative risk, 1.63; 95% confidence interval, 1.25-2.11) and death (relative risk, 2.36; 95% confidence interval, 1.15-4.81). CONCLUSION: We found that pregnant women with comorbidities including diabetes mellitus, hypertension, and cardiovascular disease were at increased risk for severe COVID-19-related outcomes, maternal morbidities, and adverse birth outcomes. We also identified several less commonly known risk factors, including HIV infection, prepregnancy underweight, and anemia. Although pregnant women are already considered a high-risk population, special priority for prevention and treatment should be given to pregnant women with these additional risk factors.

Transcranial Direct Current Stimulation Enhances Neuroplasticity and Accelerates Motor Recovery in a Stroke Mouse Model.

BACKGROUND: More effective strategies are needed to promote poststroke functional recovery. Here, we evaluated the impact of bihemispheric transcranial direct current stimulation (tDCS) on forelimb motor function recovery and the underlying mechanisms in mice subjected to focal ischemia of the motor cortex. METHODS: Photothrombotic stroke was induced in the forelimb brain motor area, and tDCS was applied once per day for 3 consecutive days, starting 72 hours after stroke. Grid-walking, single pellet reaching, and grip strength tests were conducted to assess motor function. Local field potentials were recorded to evaluate brain connectivity. Western immunoblotting, ELISA, quantitative real-time polymerase chain reaction, and Golgi-Cox staining were used to uncover tDCS-mediated stroke recovery mechanisms. RESULTS: Among our results, tDCS increased the rate of motor recovery, anticipating it at the early subacute stage. In this window, tDCS enhanced BDNF (brain-derived neurotrophic factor) expression and dendritic spine density in the peri-infarct motor cortex, along with increasing functional connectivity between motor and somatosensory cortices. Treatment with the BDNF TrkB (tropomyosin-related tyrosine kinase B) receptor inhibitor, ANA-12, prevented tDCS effects on motor recovery and connectivity as well as the increase of spine density, pERK (phosphorylated extracellular signal-regulated kinase), pCaMKII (phosphorylated calcium/calmodulin-dependent protein kinase II), pMEF (phosphorylated myocyte-enhancer factor), and PSD (postsynaptic density)-95. The tDCS-promoted rescue was paralleled by enhanced plasma BDNF level, suggesting its potential role as circulating prognostic biomarker. CONCLUSIONS: The rate of motor recovery is accelerated by tDCS applied in the subacute phase of stroke. Anticipation of motor recovery via vicariate pathways or neural reserve recruitment would potentially enhance the efficacy of standard treatments, such as physical therapy, which is often delayed to a later stage when plastic responses are progressively lower.

The relationship between markers of antenatal iron stores and birth outcomes differs by malaria prevention regimen-a prospective cohort study.

BACKGROUND: Iron deficiency (ID) has been associated with adverse pregnancy outcomes, maternal anaemia, and altered susceptibility to infection. In Papua New Guinea (PNG), monthly treatment with sulphadoxine-pyrimethamine plus azithromycin (SPAZ) prevented low birthweight (LBW; <2500 g) through a combination of anti-malarial and non-malarial effects when compared to a single treatment with SP plus chloroquine (SPCQ) at first antenatal visit. We assessed the relationship between ID and adverse birth outcomes in women receiving SPAZ or SPCQ, and the mediating effects of malaria infection and haemoglobin levels during pregnancy. METHODS: Plasma ferritin levels measured at antenatal enrolment in a cohort of 1892 women were adjusted for concomitant inflammation using C-reactive protein and α-1-acid glycoprotein. Associations of ID (defined as ferritin <15 µg/L) or ferritin levels with birth outcomes (birthweight, LBW, preterm birth, small-for-gestational-age birthweight [SGA]) were determined using linear or logistic regression analysis, as appropriate. Mediation analysis assessed the degree of mediation of ID-birth outcome relationships by malaria infection or haemoglobin levels. RESULTS: At first antenatal visit (median gestational age, 22 weeks), 1256 women (66.4%) had ID. Overall, ID or ferritin levels at first antenatal visit were not associated with birth outcomes. There was effect modification by treatment arm. Amongst SPCQ recipients, ID was associated with a 81-g higher mean birthweight (95% confidence interval [CI] 10, 152; P = 0.025), and a twofold increase in ferritin levels was associated with increased odds of SGA (adjusted odds ratio [aOR] 1.25; 95% CI 1.06, 1.46; P = 0.007). By contrast, amongst SPAZ recipients, a twofold increase in ferritin was associated with reduced odds of LBW (aOR 0.80; 95% CI 0.67, 0.94; P = 0.009). Mediation analyses suggested that malaria infection or haemoglobin levels during pregnancy do not substantially mediate the association of ID with birth outcomes amongst SPCQ recipients. CONCLUSIONS: Improved antenatal iron stores do not confer a benefit for the prevention of adverse birth outcomes in the context of malaria chemoprevention strategies that lack the non-malarial properties of monthly SPAZ. Research to determine the mechanisms by which ID protects from suboptimal foetal growth is needed to guide the design of new malaria prevention strategies and to inform iron supplementation policy in malaria-endemic settings. TRIAL REGISTRATION: ClinicalTrials.gov NCT01136850 .

Enhancing Plasticity Mechanisms in the Mouse Motor Cortex by Anodal Transcranial Direct-Current Stimulation: The Contribution of Nitric Oxide Signaling.

Consistent body of evidence shows that transcranial direct-current stimulation (tDCS) over the primary motor cortex (M1) facilitates motor learning and promotes recovery after stroke. However, the knowledge of molecular mechanisms behind tDCS effects needs to be deepened for a more rational use of this technique in clinical settings. Here we characterized the effects of anodal tDCS of M1, focusing on its impact on glutamatergic synaptic transmission and plasticity. Mice subjected to tDCS displayed increased long-term potentiation (LTP) and enhanced basal synaptic transmission at layer II/III horizontal connections. They performed better than sham-stimulated mice in the single-pellet reaching task and exhibited increased forelimb strength. Dendritic spine density of layer II/III pyramidal neurons was also increased by tDCS. At molecular level, tDCS enhanced: 1) BDNF expression, 2) phosphorylation of CREB, CaMKII, and GluA1, and 3) S-nitrosylation of GluA1 and HDAC2. Blockade of nitric oxide synthesis by L-NAME prevented the tDCS-induced enhancement of GluA1 phosphorylation at Ser831 and BDNF levels, as well as of miniature excitatory postsynaptic current (mEPSC) frequency, LTP and reaching performance. Collectively, these findings demonstrate that anodal tDCS engages plasticity mechanisms in the M1 and highlight a role for nitric oxide (NO) as a novel mediator of tDCS effects.

"An unnecessary cut?" multilevel health systems analysis of drivers of caesarean sections rates in Italy: a systematic review.

BACKGROUND: Improvements in medical technologies have seen over-medicalization of childbirth. Caesarean section (CS) is a lifesaving procedure proven effective in reducing maternal and perinatal mortality across the globe. However, as with any medical procedure, the CS intrinsically carries some risk to its beneficiaries. In recent years, CS rates have risen alarmingly in high-income countries. Many exceeding the World Health Organisation (WHO) recommendation of a 10 to 15% annual CS rate. While this situation poses an increased risk to women and their children, it also represents an excess human and financial burden on health systems. Therefore, from a health system perspective this study systematically summarizes existing evidence relevant to the factors driving the phenomenon of increasing CS rates using Italy as a case study. METHODS: Employing the WHO Health System Framework (WHOHSF), this systematic review used the PRISMA guidelines to report findings. PubMed, SCOPUS, MEDLINE, Cochrane Library and Google Scholar databases were searched up until April 1, 2020. Findings were organised through the six dimensions of the WHOHSF framework: service delivery, health workforce, health system information; medical products vaccine and technologies, financing; and leadership and governance. RESULTS: CS rates in Italy are affected by complex interactions among several stakeholder groups and contextual factors such as the hyper-medicalisation of delivery, differences in policy and practice across units and the national context, issues pertaining to the legal and social environment, and women's attitudes towards pregnancy and childbirth. CONCLUSION: Mitigating the high rates of CS will require a synergistic multi-stakeholder intervention. Specifically, with processes able to attract the official endorsement of policy makers, encourage concensus between regional authorities and local governments and guide the systematic compliance of delivery units with its clinical guidelines.

Chromatographic analysis of VOC patterns in exhaled breath from smokers and nonsmokers.

Cigarette smoking harms nearly every organ of the body and causes many diseases. The analysis of exhaled breath for exogenous and endogenous volatile organic compounds (VOCs) can provide fundamental information on active smoking and insight into the health damage that smoke is creating. Various exhaled VOCs have been reported as typical of smoking habit and recent tobacco consumption, but to date, no eligible biomarkers have been identified. Aiming to identify such potential biomarkers, in this pilot study we analyzed the chemical patterns of exhaled breath from 26 volunteers divided into groups of nonsmokers and subgroups of smokers sampled at different periods of withdrawal from smoking. Solid-phase microextraction technique and gas chromatography/mass spectrometry methods were applied. Many breath VOCs were identified and quantified in very low concentrations (ppbv range), but only a few (toluene, pyridine, pyrrole, benzene, 2-butanone, 2-pentanone and 1-methyldecyclamine) were found to be statistically significant variables by Mann-Whitney test. In our analysis, we did not consider the predictive power of individual VOCs, as well as the criterion of uniqueness for biomarkers suggests, but we used the patterns of the only statistically significant compounds. Probit prediction model based on statistical relevant VOCs-patterns showed that assessment of smoking status is heavily time dependent. In a two-class classifier model, it is possible to predict with high specificity and sensitivity if a subject is a smoker who respected 1 hour of abstinence from smoking (short-term exposure to tobacco) or a smoker (labelled "blank smoker") after a night out of smoking (long-term exposure to tobacco). On the other side, in our study "blank smokers" are more like non-smokers so that the two classes cannot be well distinguished and the corresponding prediction results showed a good sensitivity but low selectivity.

Contrast-enhanced Mammography versus MR Imaging of the Breast.

Breast MR imaging and contrast-enhanced mammography (CEM) are both techniques that employ intravenously injected contrast agent to assess breast lesions. This approach is associated with a very high sensitivity for malignant lesions that typically exhibit rapid enhancement due to the leakiness of neovasculature. CEM may be readily available at the breast imaging department and can be performed on the spot. Breast MR imaging provides stronger enhancement than the x-ray-based techniques and offers higher sensitivity. From a patient perspective, both modalities have their benefits and downsides; thus, patient preference could also play a role in the selection of the imaging technique.

Is the mental health of couples with twins more at risk? Results from an Italian cohort study.

Introduction: Our retrospective study aimed to investigate whether parents of twins encounter heightened psychological and emotional distress one year after childbirth, in comparison to parents of singletons within an Italian cohort. Methods: Exclusion criteria included multiparity, preterm birth, congenital anomalies, stillbirth, >2 fetus pregnancies, and pre-existing maternal mental health disorders. Out of the 300 couples (600 parents) invited to participate, 286 parents (158 mothers, 128 fathers) successfully completed a self-administered survey. We analyzed three scores separately for mothers and fathers, differentiating between singleton and twin pregnancies: the Edinburgh Postnatal Depression Scale (EPDS) score, the State and Trait Anxiety Inventory (STAI)-Y1 score, and the STAI-Y2 score. Results: Logistic models were used to assess the influence of age, BMI, marital status, education, and employment on the three binary scores (EPDS, STAI-Y1, and STAI-Y2), revealing no significant differences in absolute scores between parents of singletons and twins. Paired analysis revealed significantly higher EPDS (mean increase: 3.8, SD: 6.5), STAI-Y1 (mean increase: 5.4, SD: 12.5), and STAI-Y2 (mean increase: 4.5, SD: 12.4) scores for mothers (p < 0.0001). Approximately 10% of women and 8% of men reported suicidal thoughts. Discussion: Contrary to expectations, no substantial psychological differences emerged between parents of twins and singletons. Adjusting for confounders through univariate analysis maintained nonsignificant trends. Nevertheless, caution in interpretation is warranted due to strict inclusion criteria favoring twin pregnancies with better outcomes. Unintended bias could have resulted from routine psychological support offered to mothers of twins in our clinic. This presents an important framework for future research, including randomized controlled trials comparing parents of multiples with psychological support to those without.Finally, the elevated prevalence of depression symptoms and suicidal thoughts in our cohort underscores the importance of mental health during pregnancy and early parenting. We advocate for the screening of parents for postpartum depression and various psychological conditions, encompassing a spectrum of anxiety disorders. Those at elevated risk of mental distress should be proactively offered appropriate support.

An LC-MS/MS method for the determination of drugs of abuse included THC-COOH, EtG, and NPS, using a single hair extraction sample.

Hair analysis plays an important role in the determination of drugs of abuse in both forensic and clinical toxicology investigations. The analysis of different substances often requires the use of different sample preparation methods, thereby increasing the amount of hair sample and time required. In the present study, a fast method involving a combination of a single 25 mg hair extraction procedure and four liquid chromatography-tandem mass spectrometry methods using the same chromatographic phases and column was developed and validated. The target was the identification and quantification of various commonly abused drugs and their metabolites, including amphetamines, cocaine, opioids, cannabinoids, THC-COOH and EtG, and more than 140 new psychoactive substances, including synthetic cannabinoids, phenethylamines, synthetic opioids, methylphenidate, cathinone, piperidine, and tryptamines.

Risk factors associated with severe perineal lacerations during vaginal delivery: a 10-year propensity score-matched observational study.

BACKGROUND: Severe perineal lacerations are rare obstetrical complications in high-income countries. However, the prevention of obstetric anal sphincter injuries is crucial because of their long-term consequences on a woman's digestive function, sexual-mental health, and well-being. The probability of obstetric anal sphincter injuries can be predicted by assessing antenatal and intrapartum risk factors. OBJECTIVE: This study aimed to assess the incidence of obstetric anal sphincter injuries at a single institution for 10 years and to identify women more at risk by evaluating the relationship between antenatal and intrapartum risk factors and severe perineal tears. The main outcome measured in this study was the occurrence of obstetric anal sphincter injuries during vaginal delivery. STUDY DESIGN: This was an observational retrospective cohort study conducted at a University Teaching Hospital in Italy. The study was conducted from 2009 to 2019 using a prospectively maintained database. The study cohort included all women with singleton pregnancy at term who delivered via vaginal delivery in cephalic presentation. Of note, data analysis was performed in 2 stages: a propensity score matching to balance possible differences between patients with obstetric anal sphincter injuries and those without and a stepwise univariate and multivariate logistic regression. A secondary analysis was performed to further evaluate the effect of parity, epidural anesthesia, and duration of the second stage of labor by adjusting for potential confounders. RESULTS: Of 41,440 patients screened for eligibility, 22,156 met the inclusion criteria, and 15,992 were balanced after propensity score matching. Obstetric anal sphincter injuries occurred in 81 cases (0.4%), 67 (0.3%) after spontaneous delivery and 14 (0.8%) after vacuum delivery(P=.002). There was an increased odds of severe lacerations of nearly 2-fold for nulliparous women delivering by vacuum delivery (adjusted odds ratio, 2.85; 95% confidence interval, 1.19-6.81; P=.019), with a reciprocal reduction in women with spontaneous vaginal delivery (adjusted odds ratio, 0.35; 95% confidence interval, 0.15-0.84; P=.019) and at least 1 previous delivery (adjusted odds ratio, 0.51; 95% confidence interval, 0.31-0.85; P=.005). Epidural anesthesia was associated with a lower incidence of obstetric anal sphincter injuries (adjusted odds ratio, 0.54; 95% confidence interval, 0.33-0.86; P=.011). The risk of severe lacerations was independent of the duration of the second stage of labor (adjusted odds ratio, 1.00; 95% confidence interval, 0.99-1.00; P=.3), whereas the risk was reduced when mediolateral episiotomy was performed (adjusted odds ratio, 0.20; 95% confidence interval, 0.11-0.36; P<.001). Neonatal risk factors include head circumference (odds ratio, 1.50; 95% confidence interval, 1.18-1.90; P=.001) and vertex malpresentation (adjusted odds ratio, 2.71; 95% confidence interval, 1.08-6.78; P=.033). Induction of labor (adjusted odds ratio, 1.13; 95% confidence interval, 0.72-1.92; P=.6), frequent obstetrical examinations (adjusted odds ratio, 1.17; 95% confidence interval, 0.72-1.90), and women's supine position at birth (adjusted odds ratio, 1.25; 95% confidence interval, 0.61-2.55; P=.5) were further evaluated. Among severe obstetrical complications, shoulder dystocia increased the risk of obstetric anal sphincter injuries by nearly 4 times (adjusted odds ratio, 3.92; 95% confidence interval, 0.50-30.74; P=.2), whereas postpartum hemorrhage occurred 3 times more often in cases of delivery complicated by severe lacerations (adjusted odds ratio, 3.35; 95% confidence interval, 1.76-6.40; P<.001). The relationship among obstetric anal sphincter injuries, parity, and the use of epidural anesthesia was further confirmed in a secondary analysis. We found that primiparas who delivered without epidural anesthesia had the highest risk of obstetric anal sphincter injuries (adjusted odds ratio, 2.53; 95% confidence interval, 1.46-4.39; P=.001). CONCLUSION: Severe perineal lacerations were found to be a rare complication of vaginal delivery. By using a robust statistical model, such as propensity score matching, we were able to investigate a broad range of antenatal and intrapartum risk factors, including use of epidural anesthesia, number of obstetrics examinations, and patient position at birth, which are usually underreported. Moreover, we found that women who delivered for the first time without epidural anesthesia had the highest risk of obstetric anal sphincter injuries.

Image-Guided Localization Techniques for Metastatic Axillary Lymph Nodes in Breast Cancer; What Radiologists Should Know.

Targeted axillary dissection (TAD) is an axillary staging technique after NACT that involves the removal of biopsy-proven metastatic lymph nodes in addition to sentinel lymph node biopsy (SLNB). This technique avoids the morbidity of traditional axillary lymph node dissection and has shown a lower false-negative rate than SLNB alone. Therefore, marking positive axillary lymph nodes before NACT is critical in order to locate and remove them in the subsequent surgery. Current localization methods include clip placement with intraoperative ultrasound, carbon-suspension liquids, localization wires, radioactive tracer-based localizers, magnetic seeds, radar reflectors, and radiofrequency identification devices. The aim of this paper is to illustrate the management of axillary lymph nodes based on current guidelines and explain the features of axillary lymph node markers, with relative advantages and disadvantages.

Dose-response Analysis in Hepatic Tumors Treated with 90Y-TARE According to a Personalized Dosimetric Workflow: Preliminary Results.

BACKGROUND: Transarterial Radioembolization (TARE) is a widespread radiation therapy for unresectable hepatic lesions, but a clear understanding of the dose-response link is still missing. The aim of this preliminary study is to investigate the role of both dosimetric and clinical parameters as classifiers or predictors of response and survival for TARE in hepatic tumors and to present possible response cut-off. METHODS: 20 patients treated with glass or resin microspheres according to a personalized workflow were included. Dosimetric parameters were extracted from personalized absorbed dose maps obtained from the convolution of 90Y PET images with 90Y voxel S-values. RESULTS: D95 ≥ 104 Gy and tumor mean absorbed dose MADt ≥ 229 Gy were found to be optimal cut-off values for complete response, while D30 ≥ 180 Gy and MADt ≥ 117 Gy were selected as cut-off values for at least partial response and predicted better survival. Clinical parameters Alanine Transaminase (ALT) and Model for End-Stage Liver Disease (MELD) didn't show sufficient classification capability for response or survival. CONCUSION: These preliminary results highlight the importance of an accurate dosimetric evaluation and suggest a cautious approach when considering clinical indicators. Dosimetric cut-off values could be a support tool in both planning and post-treatment phases. Larger multi-centric randomized trials, with standardized methods regarding patient selection, response criteria, Regions of Interest definition, dosimetric approach and activity planning are needed to confirm these promising results.

Long-term outcomes of COVID-19 vaccination in patients with rare and complex connective tissue diseases: The ERN-ReCONNET VACCINATE study.

Background: Vaccination is one of the most important measures to contain the COVID-19 pandemic, especially for frail patients. VACCINATE is a multicentre prospective observational study promoted by the European Reference Network on Rare and Complex Connective Tissue and Musculoskeletal Diseases (ERN ReCONNET) aimed at assessing the long-term outcomes of COVID-19 vaccination in patients with rare and complex connective tissue diseases (rcCTDs) in terms of efficacy and safety. Methods: Adult rcCTDs patients were eligible for recruitment. Demographic, clinical and vaccination data were collected at enrolment. Follow-up visits were scheduled 4, 12, 24, 36 and 48 weeks after completion of the first vaccination cycle; data on adverse events, disease exacerbations and the occurrence of new SARS-CoV-2 infections were collected at these time-points. Findings: 365 rcCTDs patients (87 % female, mean age 51.8 ± 14.6 years) were recruited. Overall, 200 patients (54.8 %) experienced at least one adverse event, generally mild and in most cases occurring early after the vaccination. During follow-up, 55 disease exacerbations were recorded in 39 patients (10.7 %), distributed over the entire observation period, although most frequently within 4 weeks after completion of the vaccination cycle. The incidence of new SARS-CoV-2 infections was 8.9 per 1000 person-months, with no cases within 12 weeks from vaccine administration and an increasing trend of infections moving away from the primary vaccination cycle. Only one case of severe COVID-19 was reported during the study period. Interpretation: COVID-19 vaccination seems effective and safe in rcCTDs patients. The rate of new infections was rather low and serious infections were uncommon in our cohort. No increased risk of disease flares was observed compared to previous disease history; however, such exacerbations may be potentially severe, emphasising the need for close monitoring of our patients.

Adverse maternal, fetal, and newborn outcomes among pregnant women with SARS-CoV-2 infection: an individual participant data meta-analysis.

INTRODUCTION: Despite a growing body of research on the risks of SARS-CoV-2 infection during pregnancy, there is continued controversy given heterogeneity in the quality and design of published studies. METHODS: We screened ongoing studies in our sequential, prospective meta-analysis. We pooled individual participant data to estimate the absolute and relative risk (RR) of adverse outcomes among pregnant women with SARS-CoV-2 infection, compared with confirmed negative pregnancies. We evaluated the risk of bias using a modified Newcastle-Ottawa Scale. RESULTS: We screened 137 studies and included 12 studies in 12 countries involving 13 136 pregnant women.Pregnant women with SARS-CoV-2 infection-as compared with uninfected pregnant women-were at significantly increased risk of maternal mortality (10 studies; n=1490; RR 7.68, 95% CI 1.70 to 34.61); admission to intensive care unit (8 studies; n=6660; RR 3.81, 95% CI 2.03 to 7.17); receiving mechanical ventilation (7 studies; n=4887; RR 15.23, 95% CI 4.32 to 53.71); receiving any critical care (7 studies; n=4735; RR 5.48, 95% CI 2.57 to 11.72); and being diagnosed with pneumonia (6 studies; n=4573; RR 23.46, 95% CI 3.03 to 181.39) and thromboembolic disease (8 studies; n=5146; RR 5.50, 95% CI 1.12 to 27.12).Neonates born to women with SARS-CoV-2 infection were more likely to be admitted to a neonatal care unit after birth (7 studies; n=7637; RR 1.86, 95% CI 1.12 to 3.08); be born preterm (7 studies; n=6233; RR 1.71, 95% CI 1.28 to 2.29) or moderately preterm (7 studies; n=6071; RR 2.92, 95% CI 1.88 to 4.54); and to be born low birth weight (12 studies; n=11 930; RR 1.19, 95% CI 1.02 to 1.40). Infection was not linked to stillbirth. Studies were generally at low or moderate risk of bias. CONCLUSIONS: This analysis indicates that SARS-CoV-2 infection at any time during pregnancy increases the risk of maternal death, severe maternal morbidities and neonatal morbidity, but not stillbirth or intrauterine growth restriction. As more data become available, we will update these findings per the published protocol.

A novel human biomonitoring study by semiconductor gas sensors in Exposomics: investigation of health risk in contaminated sites.

Two areas in central-southern Italy Land of Fires in Campania and Valley of Sacco river in Lazio are known to be contaminated sites, the first due to illegal fly-tipping and toxic fires, and the second due to an intensive industrial exploitation done by no-scruple companies and crooked public administration offices with dramatic consequences for environment and resident people. The work is intended to contribute to Human BioMonitoring (HBM) studies conducted in these areas on healthy young male population by a semiconductor gas sensor array trained by SPME-GC/MS. Human semen, blood and urine were investigated. The fingerprinting of the Volatile Organic Compounds (VOCs) by a gas sensors system allowed to discriminate the different contamination of the two areas and was able to predict the chemical concentration of several VOCs identified by GC/MS.

The Effect of Epidural Analgesia on Labour and Neonatal and Maternal Outcomes in 1, 2a, 3, and 4a Robson's Classes: A Propensity Score-Matched Analysis.

Background: Lumbar epidural analgesia (EA) is the most commonly used method for reducing labour pain, but its impact on the duration of the second stage of labour and on neonatal and maternal outcomes remains a matter of debate. Our aim was to examine whether EA affected the course and the outcomes of labour among patients divided according to the Robson-10 group classification system. Methods: Patients of Robson's classes 1, 2a, 3, and 4a were divided into either the EA group or the non-epidural analgesia (NEA) group. A propensity score-matching analysis was performed to balance the intergroup differences. The primary goal was to analyse the duration of the second stage of labour. The secondary goals were to evaluate neonatal and maternal outcomes. Results: In total, 21,808 cases were analysed. The second stage of labour for all groups was prolonged using EA (p < 0.05) without statistically significant differences in neonatal outcomes. EA resulted in a lower rate of episiotomies in nulliparous patients, with a higher rate of operative vaginal deliveries (OVD) (p < 0.05) and Caesarean sections (CS) (p < 0.05) in some classes. Conclusions: EA prolonged the duration of labour without affecting neonatal outcomes and reduced the rate of episiotomies, but also increased the rate of OVDs.

Molecular Alterations and Severe Abnormalities in Spermatozoa of Young Men Living in the "Valley of Sacco River" (Latium, Italy): A Preliminary Study.

The Valley of Sacco River (VSR) (Latium, Italy) is an area with large-scale industrial chemical production that has led over time to significant contamination of soil and groundwater with various industrial pollutants, such as organic pesticides, dioxins, organic solvents, heavy metals, and particularly, volatile organic compounds (VOCs). In the present study, we investigated the potential impact of VOCs on the spermatozoa of healthy young males living in the VSR, given the prevalent presence of several VOCs in the semen of these individuals. To accomplish this, spermiograms were conducted followed by molecular analyses to assess the content of sperm nuclear basic proteins (SNBPs) in addition to the protamine-histone ratio and DNA binding of these proteins. We found drastic alterations in the spermatozoa of these young males living in the VSR. Alterations were seen in sperm morphology, sperm motility, sperm count, and protamine/histone ratios, and included significant reductions in SNBP-DNA binding capacity. Our results provide preliminary indications of a possible correlation between the observed alterations and the presence of specific VOCs.

Efficacy and Accuracy of Using Magnetic Seed for Preoperative Non-Palpable Breast Lesions Localization: Our Experience with Magseed.

In this retrospective study we share our single-center experience using a magnetic seed for the preoperative localization of non-palpable breast lesions. Patients who underwent a preoperative localization with Magseed® (Endomagnetics, Cambridge, UK) placement between 2020 and 2022 were enrolled. Indications to Magseed placement have been established during multidisciplinary meetings prior to surgery and all patients underwent breast-conserving surgery (BCS). 45 patients were included. Magnetic seeds have been introduced under ultrasound guidance in 40 patients (88.9%) and under stereotactic guidance in 5 patients (11.1%). We registered a highly successful placement rate (97.8%), with only one case of migration (2.2%). After BCS, all the magnetic seeds were recovered (100% retrieval rate). The re-excision rate for positive margins was 0%. Our experience, with a highly successful placement and retrieval rate and a re-excision rate equal to 0%, is consistent with the encouraging literature published on Magseed so far, suggesting this technique to be extremely effective. Moreover, our single case of seed migration supports the existing data stating that Magseed migration is rare. In conclusion, despite acknowledging Magseed limitations, we highly value the advantages linked to this technique, and we, therefore, uphold its use.

Protocol for a sequential, prospective meta-analysis to describe coronavirus disease 2019 (COVID-19) in the pregnancy and postpartum periods.

We urgently need answers to basic epidemiological questions regarding SARS-CoV-2 infection in pregnant and postpartum women and its effect on their newborns. While many national registries, health facilities, and research groups are collecting relevant data, we need a collaborative and methodologically rigorous approach to better combine these data and address knowledge gaps, especially those related to rare outcomes. We propose that using a sequential, prospective meta-analysis (PMA) is the best approach to generate data for policy- and practice-oriented guidelines. As the pandemic evolves, additional studies identified retrospectively by the steering committee or through living systematic reviews will be invited to participate in this PMA. Investigators can contribute to the PMA by either submitting individual patient data or running standardized code to generate aggregate data estimates. For the primary analysis, we will pool data using two-stage meta-analysis methods. The meta-analyses will be updated as additional data accrue in each contributing study and as additional studies meet study-specific time or data accrual thresholds for sharing. At the time of publication, investigators of 25 studies, including more than 76,000 pregnancies, in 41 countries had agreed to share data for this analysis. Among the included studies, 12 have a contemporaneous comparison group of pregnancies without COVID-19, and four studies include a comparison group of non-pregnant women of reproductive age with COVID-19. Protocols and updates will be maintained publicly. Results will be shared with key stakeholders, including the World Health Organization (WHO) Maternal, Newborn, Child, and Adolescent Health (MNCAH) Research Working Group. Data contributors will share results with local stakeholders. Scientific publications will be published in open-access journals on an ongoing basis.