Sudden unexpected postnatal collapse and BUB1B mutation: first forensic case report.

Sudden unexpected postnatal collapse (SUPC) is a sudden collapse of the clinical conditions of a full-term or near-term newborn, within the first 7 days of life, that requires resuscitation with positive ventilation and who either dies, has hypoxic-ischemic encephalopathy, or requires intensive care. The incidence of SUPC is very low, and most often presents a negative prognosis. The BUB1B gene is a mitotic checkpoint of serine/threonine kinase B that encodes a protein crucial for maintaining the correct number of chromosomes during cell division. Mutations in the BUB1B gene are linked to mosaic variegated aneuploidy syndrome 1 (MVA1), a rare autosomal recessive disorder characterized by diffuse mosaic aneuploidies involving several chromosomes and tissues. This paper discusses a case of a newborn who had a spontaneous delivery. After 2 h and 10 min, the infant showed generalized hypotonia and cyanosis, and his doctors performed orotracheal intubation, cardiac massage, pharmacological hemodynamic therapy, mechanical ventilation, antibiotic therapy, and hypothermic treatment. The newborn was discharged after 5 months with the diagnosis of hypoxic-ischemic encephalopathy. Suspecting an SUPC, a complete genetic analysis was performed demonstrating a compound heterozygous mutations in the BUB1B gene. The newborn died at 6 months of life, 1 month after discharge. A complete autopsy was performed, determining that the cause of death was due to sepsis starting from a brocopneumonic process, with outcomes of hypoxic-ischemic encephalopathy (HIE). In this scenario, it is not possible to demonstrate the causal effect of this mutation, considering that it could play a causal or concausal role in the onset of SUPC. Further research based on multicenter studies, as well as on animal models, could be very useful to clarify the pathological effect of this mutation.

Circulating tumor DNA as a biomarker for predicting progression-free survival and overall survival in patients with epithelial ovarian cancer: a systematic review and meta-analysis.

OBJECTIVES: Circulating tumor DNA (ctDNA) is emerging as a potential prognostic biomarker in multiple tumor types. However, despite the many studies available on small series of patients with ovarian cancer, a recent systematic review and meta-analysis is lacking. The objective of this study was to determine the association of ctDNA with progression-free-survival and overall survival in patients with epithelial ovarian cancer. METHODS: An electronic search was conducted using PubMed (MEDLINE), Embase, CENTRAL (Cochrane Library), and CINAHL-Complete from January 2000 to September 15, 2023. To be included in the analysis the studies had to meet the following pre-specified inclusion criteria: (1) evaluable ctDNA; (2) progression-free-survival and overall survival reported as hazard ratio (HR); and (3) the patient population had epithelial ovarian cancer at the time of ctDNA detection. We evaluated the association of ctDNA with progression-free survival and overall survival. Secondary outcomes focused on sub-group analysis of genomic alterations and international Federation of Gynecology and Obstetrics (FIGO) stage. RESULTS: A total of 26 studies reporting on 1696 patients with epithelial ovarian cancer were included. The overall concordance rate between plasma-based and tissue-based analyses was approximately 62%. We found that a high level of ctDNA in epithelial ovarian cancer was associated with worse progression-free survival (HR 5.31, 95% CI 2.14 to 13.17, p<0.001) and overall survival (HR 2.98, 95% CI 1.86 to 4.76, p<0.0001). The sub-group analysis showed a greater than threefold increase in the risk of relapse in patients with positive HOXA9 meth-ctDNA (HR 3.84, 95% CI 1.57 to 9.41, p=0.003). CONCLUSIONS: ctDNA was significantly associated with worse progression-free survival and overall survival in patients with epithelial ovarian cancer. Further prospective studies are needed. PROSPERO REGISTRATION NUMBER: CRD42023469390.

A Longitudinal Multiinstitutional Study of Vulvar Lichen Sclerosus: From Childhood to Perimenopause.

OBJECTIVE: The main outcome of this study was the evaluation of clinical characteristics, comorbidities, and therapeutic approaches in patients with vulvar lichen sclerosus (VLS) aged from childhood to perimenopause. Secondly, it was intended to compare these characteristics according to the menarchal status. METHODS: Patients less than 45 years of age with a diagnosis of VLS from January 2002 to June 2022 in 10 referral centers were included in this retrospective longitudinal study. The univariate analysis compared the dependent variables according to menarchal status. RESULTS: One hundred eighty-six patients met the inclusion criteria. At diagnosis, between 25% and 40% of premenarchal patients reported signs related to subepithelial hemorrhage. A significantly greater presence of bleeding (p < .005), easy bruising (p = .028), fissures (p = .008), petechiae/splinter hemorrhages (p < .001), and bleeding/blistering or open sores (p = .011) was observed in premenarchal patients with respect to the postmenarchal group. The perineum (p = .013) and the perianal region (p < .001) were significantly more involved in the premenarchal group. Topical calcineurin inhibitors were more used in the premenarchal population (p = .004), whereas vitamin E oil and moisturizers were more used in the postmenarchal population (p = .047). CONCLUSIONS: Vulvar lichen sclerosus is a chronic condition that can cause vulvar changes that result in severe morbidity and affects sexual function and quality of life, even before menopause. Vulvar lichen sclerosus continues to be misdiagnosed in this population. This may lead to an average delay from symptom onset to diagnosis. Evaluating clinical manifestations of VLS in premenarchal and postmenarchal age allowed us to find different clinical characteristics between the 2 periods suggestive of the diagnosis.

Effect of Physical Activity during Pregnancy on the Risk of Hypertension Disorders and Gestational Diabetes: Evidence Generated by New RCTs and Systematic Reviews.

Hypertensive disorders of pregnancy (HDP) and gestational diabetes mellitus (GDM) are the most common medical complications in pregnancy. Physical exercise is considered to be safe and beneficial during pregnancy. Moreover, pregnancy could be considered as an opportunity for healthcare providers to promote positive lifestyle behavior and optimize the well-being of pregnant women. Since there are few up-to-date reviews evaluating the role of exercise and the risks of developing obstetrical complications, we performed a review to investigate the effects of physical activity and exercise during pregnancy compared to a control group, focusing on the risk of development of HDP and GDM. We searched Medline and Web of Science, including only randomized controlled trials (RCTs) and systematic reviews. This review supports a beneficial effect of exercise and provides evidence that it significantly decreases the risk of HDP and GDM.

Wharton's jelly-derived multifunctional hydrogels: New tools to promote intervertebral disc regeneration in vitro and ex vivo.

The degeneration of intervertebral disc (IVD) is a disease of the entire joint between two vertebrae in the spine caused by loss of extracellular matrix (ECM) integrity, to date with no cure. The various regenerative approaches proposed so far have led to very limited successes. An emerging opportunity arises from the use of decellularized ECM as a scaffolding material that, directly or in combination with other materials, has greatly facilitated the advancement of tissue engineering. Here we focused on the decellularized matrix obtained from human umbilical cord Wharton's jelly (DWJ) which retains several structural and bioactive molecules very similar to those of the IVD ECM. However, being a viscous gel, DWJ has limited ability to retain ordered structural features when considered as architecture scaffold. To overcome this limitation, we produced DWJ-based multifunctional hydrogels, in the form of 3D millicylinders containing different percentages of alginate, a seaweed-derived polysaccharide, and gelatin, denatured collagen, which may impart mechanical integrity to the biologically active DWJ. The developed protocol, based on a freezing step, leads to the consolidation of the entire polymeric dispersion mixture, followed by an ionic gelation step and a freeze-drying process. Finally, a porous, stable, easily storable, and suitable matrix for ex vivo experiments was obtained. The properties of the millicylinders (Wharton's jelly millicylinders [WJMs]) were then tested in culture of degenerated IVD cells isolated from disc tissues of patients undergoing surgical discectomy. We found that WJMs with the highest percentage of DWJ were effective in supporting cell migration, restoration of the IVD phenotype (increased expression of Collagen type 2, aggrecan, Sox9 and FOXO3a), anti-inflammatory action, and stem cell activity of resident progenitor/notochordal cells (increased number of CD24 positive cells). We are confident that the DWJ-based formulations proposed here can provide adequate stimuli to the cells present in the degenerated IVD to restart the anabolic machinery.

Innovative Ultrasound Criteria for the Diagnosis of Adenomyosis and Correlation with Symptoms: A Retrospective Re-Evaluation.

The 2022 Delphi revision of the MUSA (Morphological Uterus Sonographic Assessment) criteria for the ultrasound diagnosis of adenomyosis divides the ultrasound signs for diagnosis into direct and indirect ones, considering the presence of at least one direct sign as a mandatory criterion. This study aimed to reclassify the patients referred to the Pelvic Pain specialist outpatient clinic of the Gynecological Clinic of Udine according to the new criteria, evaluating the number of overdiagnoses and the possible correlation between the direct and indirect signs and the patients' symptoms. 62 patients affected by adenomyosis were retrospectively recruited. The patients were then re-evaluated by ultrasound and clinically. At least one direct sign of adenomyosis was found in 52 patients, while 16% of the population examined did not present any. There was no statistically significant difference between patients presenting direct signs and those presenting none for the symptoms considered. According to the new criteria, 16% of the patients examined were not affected by adenomyosis; applying the new consensus to symptomatic patients could increase false negatives. In a population of symptomatic patients, the diagnosis of adenomyosis is still highly probable even without direct ultrasound signs, given the clinical symptoms and having ruled out other causes of such symptoms.

Telemedicine in the treatment of gestational diabetes: An observational cohort study on pregnancy outcomes and maternal satisfaction.

AIMS: Gestational diabetes treatment requires several outpatient consultations from diagnosis until delivery in order to prevent hyperglycaemia, which is associated with maternal and fetal complications. There is limited evidence in the literature about telemedicine superiority in improving pregnancy outcomes for women with gestational diabetes. The primary aim of the study was to evaluate maternal and fetal outcomes, while the secondary aim was to estimate the degree of satisfaction with gestational diabetes treatment, comparing telemedicine versus outpatient care. METHODS: This observational cohort study involved 60 consecutive women with gestational diabetes treated at the Diabetology Unit of Ferrara: 27 were followed up through a weekly remote control method (telemedicine group) and 33 in ambulatory clinics every 2 or 3 weeks (conventional group). After giving birth, 56 women responded to the modified Oxford Maternity Diabetes Treatment Satisfaction Questionnaire to assess their satisfaction with diabetes care. RESULTS: No statistically significant differences were found in most of the maternal and neonatal parameters evaluated in both groups. The questionnaire scores were positive in all areas investigated. Telemedicine follow-up made women feel more controlled (p = 0.045) and fit better with their lifestyle (p = 0.005). It also emerged that almost all women treated with telemedicine would recommend this method to a relative or a friend. CONCLUSIONS: Telemedicine follow-up proved to be safe both in terms of metabolic control and pregnancy outcomes; furthermore, it significantly decreased the need for outpatient consultations and increased women's satisfaction. Studying the impact of telemedicine is also necessary, considering the current difficulties associated with the Sars-COV-2 pandemic.

Pressurized intraperitoneal aerosol chemotherapy (PIPAC) with cisplatin and doxorubicin in patients with ovarian cancer: A systematic review.

BACKGROUND: PIPAC consists in delivering normothermic chemotherapy solution directly into the peritoneal cavity as an aerosol under pressure. Currently PIPAC is considered as a palliative treatment for patients suffering from non-resectable peritoneal carcinomatosis. We performed a SR to assess tolerance and response of this novel method among patient with OC. METHODS: We searched electronic database PubMed, Embase, Web of Science, Clinical Trials.gov. We only included clinical studies reporting PIPAC with cisplatin and doxorubicin in patients with ovarian cancer. RESULTS: This systematic review included 4 studies. In 3 studies all patients were pretreated with cytoreductive surgery, in 1 study surgery was performed in 8/34 (23 %) patients. Mean PCI at first PIPAC procedure ranged from 16.3 to 19.6. All studies reported the proportion of patients with ascites at the first PIPAC with a pooled rate of 48,3 %. Pooled rate of CTCAE Grade 3 toxicity calculated on the total number of PIPAC was 6 % and Grade 4 was 0.9 %. One study reported two cases of small bowel perforation related or potentially related to PIPAC. On study reported a cumulative survival after 400 days of 62 % and a mean actuarial survival time of all patients who underwent PIPAC of 442 days. In another study the mean time to progression was 144 days (95 % CI 122-168 days). CONCLUSION: This systematic review demonstrated that PIPAC with cisplatin and doxorubicin appear to have a good safety profile with low toxicity and encouraging trend in terms of overall survival.

Safety of misoprostol vs dinoprostone for induction of labor: A systematic review and meta-analysis.

OBJECTIVE: Pharmacological agents such as prostaglandins (dinoprostone and misoprostol) are commonly used to reduce the duration of labor and promote vaginal delivery. However, key safety considerations with its use include an increased risk of uterine rupture, tachysystole and hyperstimulation of pregnant women, which could potentially lead to a non-reassuring fetal heart rate and to fetal hypoxemia. The aim of this systematic review was to assess maternal and fetal outcomes between misoprostol group (PGE1) and dinoprostone group (PGE2) STUDY DESIGN: We search on MEDLINE (PubMed), CINHAL (EBSCOhost), EMBASE, Scopus (Ovid), CENTRAL (January 1, 1998, to December 31, 2022). Patients were eligible if they presented at greater than 36 weeks gestation with an indication for induction of labor and a single live cephalic fetus. We conducted a meta-analysis of data for both primary (cesarean section rate, instrumental deliveries rate, tachysystole, uterine rupture, post-partum haemorrage; chorionamiositis) and secondary outcomes (Apgar at 5 min <7, meconium-stained liquor, NICU admission, infant death) using odds-ratio (OR) as a measure of effect-size. Risk of bias assessment was performed with RoB-I. We performed statistical analyses using Cochrane RevMan version 5.4 software. RESULTS: We found 39 RCTs comparing the outcomes of interest between misoprostol and dinoprostone. The pooled effect showed no statistically significant difference between the two groups in terms of cesarean section rate [OR: 0.94; 95% CI 0.84-1.05], instrumental deliveries rate [OR: 1.04; 95% CI: 0.90-1.19; p = 0.62], tachysystole [OR: 1.21; 95% CI: 0.91-1.60; p = 0.19], post-partum hemorrhage [OR: 0.85; 95% CI: 0.62-1.15p = 0.30], chorioamnionitis [OR: 0.94; 95% CI: 0.76-1.17p = 0.59], Apgar at 5 min < 7 [OR: 0.83; 95% CI: 0.61-1.12, p = 0.21], meconium-stained liquor [OR: 1.11; 95% CI: 0.97-1.27p = 0.59], NICU admission group [OR: 0.91; 95% CI: 0.77-1.09], infant death [OR: 0.57; 95% CI: 0.22-1.44]. After performing a sub-group analysis based on the type of prostaglandins administrations (oral, vaginal gel, vaginal pessary), results did not change substantially. CONCLUSIONS: This systematic review and meta-analysis demonstrate that misoprostol and dinoprostone appear to have a similar safety profile.

Oxidative Stress Markers in Human Brain and Placenta May Reveal the Timing of Hypoxic-Ischemic Injury: Evidence from an Immunohistochemical Study.

During pregnancy, reactive oxygen species (ROS) serve as crucial signaling molecules for fetoplacental circulatory physiology. Oxidative stress is thought to sustain the pathogenesis and progression of hypoxic-ischemic encephalopathy (HIE). A retrospective study was performed on the brains and placentas of fetuses and newborns between 36-42 weeks of gestation (Group_1: Fetal intrauterine deaths, Group_2: Intrapartum deaths, Group_3: Post-partum deaths, Control group sudden neonatal death); all groups were further divided into two subgroups (Subgroup_B [brain] and Subgroup_P [placenta]), and the study was conducted through the immunohistochemical investigations of markers of oxidative stress (NOX2, 8-OHdG, NT, iNOS), IL-6, and only on the brain samples, AQP4. The results for the brain samples suggest that NOX2, 8-OHdG, NT, iNOS, and IL-6 were statistically significantly expressed above the controls. iNOS was more expressed in the fetal intrauterine death (Group_1) and less expressed in post-partum death (Group_3), while in intrapartum death (Group_2), the immunoreactivity was very low. IL-6 showed the highest expression in the brain cortex of the fetal intrauterine death (Group_1), while intrapartum death (Group_2) and post-partum death (Group_3) showed weak immunoreactivity. Post-partum death (Group_3) placentas showed the highest immunoreactivity to NOX2, which was almost double that of the fetal intrauterine death (Group_1) and intrapartum death (Group_2) placentas. Placental tissues of fetal intrauterine death (Group_1) and intrapartum death (Group_2) showed higher expression of iNOS than post-partum death (Group_3), while the IL-6 expression was higher in the fetal intrauterine death (Group_1) than the post-partum death (Group_3). The AQP4 was discarded as a possible marker because the immunohistochemical reaction in the three groups of cases and the control group was negative. The goal of this study, from the point of view of forensic pathology, is to provide scientific evidence in cases of medical liability in the Obstetric field to support the clinical data of the timing of HIE.

The clinical impact of the first-trimester nuchal translucency between the 95th-99th percentiles.

OBJECTIVES: To evaluate the clinical significance of nuchal translucency (NT) between the 95th-99th percentile in terms of typical and atypical chromosomal abnormalities (ACAs), associated fetal congenital defects and postnatal outcome. METHODS: A retrospective cohort study of fetuses with NT between the 95th-99th percentile. Data regarding the rate of associated fetal defects, genetic abnormalities and postnatal outcome were collected. RESULTS: A total of 306 cases of fetuses with an NT between the 95th-99th percentiles were included. The overall rate of genetic abnormalities was 12.1% (37/306). Chromosomal abnormalities were found in 10.1% (31/306) of cases and 2% were ACA (6/306). Within this group, two were pathogenic Copy Number Variants (CNVs) and four were single gene disorders. The overall rate of fetal congenital defects was 13.7% (42/306). All ACAs were found in fetuses with congenital defects. Postnatally, a new diagnosis of a single gene disorder was made in 0.85% of cases (2/236). CONCLUSIONS: The presence of an NT between the 95th-99th percentiles carries a 10-fold increased risk of fetal defects, representing an indication for referral for a detailed fetal anatomy evaluation. The risk of ACA is mainly related to the presence of fetal defects, irrespective of the combined test risk.

Case report: Tissue positivity for SARS-CoV-2 in a preterm born infant death of thrombosis: possible intrauterine transmission.

Intrauterine transmission of SARS-CoV-2 (Severe Acute Respiratory Syndrome Corona Virus 2) is still matter of debate among scientists and there is limited information concerning this aspect of research. This could lead to severe complications of the growing fetus and, theoretically, of the newborn as well. We report the case of a male infant of 1,100 grams, born at 27th week of gestation to a SARS-CoV-2 mother, tested negative for viral detection at delivery. He was immediately admitted to neonatal Intensive Care Unit (ICU) for severe complications, where he died after 37 days by pulmonary embolism and thrombosis of the superior vena cava. After autopsy, SARS-CoV-2 N-protein and Spike RBD were detected in several tissues, particularly in the esophagus, stomach, spleen, and heart, with a significantly higher H-Score than the placenta. In conclusion, immunohistochemical analysis demonstrated SARS-CoV-2 NP and Spike RBD positivity in different tissues suggesting a possible intrauterine transmission. Newborn thrombo-embolism could be a complication of SARS-CoV-2 infection as observed in adult patients.

A survey on the current practice of indicating an elective cesarean after a previous myomectomy.

OBJECTIVE: The objective of this study was to evaluate the attitude of obstetricians/gynecologists toward indicating an elective cesarean delivery in pregnant patients with a previous myomectomy. MATERIALS AND METHODS: Web-based multiple-choice questions survey evaluating the attitude to indicate a cesarean with a composite summated score (range 56-280) from a 56-item Likert scale: score 56-112: weak attitude, 113-168: moderate, 169-224: strong, and 225-280: very strong. The reliability of the score (internal consistency) was evaluated with Cronbach's alpha coefficient. The association between the score and participants' characteristics was determined with a bivariate analysis followed by linear regression analysis. The "global importance" of each risk factor was defined as the prevalence of the answers: "moderately important", "very important", and "extremely important" on the Likert scale. Factors with a "global importance" >75% were considered "crucial" in influencing the choice to indicate a cesarean. RESULTS: One-hundred-twenty obstetricians/gynecologists responded (response rate 70.6%). The mean ± SD composite summated score was 137 ± 31; 30 (25.0%) participants presented a "weak attitude to cesarean", 68 (56.7%) a "moderate attitude", 22 (18.3%) a "strong attitude", and none a "very strong attitude". The Cronbach's alpha was 0.934 (high internal consistency). A self-reported number of myomectomies performed per year >50 was associated with a lower score (-25 points, 95% CI -50 to -1, p = 0.04). Eight criteria resulted "crucial" in indicating a cesarean: opening of the endometrial cavity, monopolar electrosurgery, time surgery-pregnancy <6 months, 2+ previous myomectomies, hematoma formation in the surgical wound, 3+ removed fibroids, and a FIGO4 or FIGO3 removed fibroid. CONCLUSIONS: Obstetricians/gynecologists are cautious to indicate a cesarean in pregnant patients with a previous myomectomy, except for cases at hypothetic high-risk for uterine rupture, mainly supported by weak evidence. Information to patients and among clinicians is crucial to avoid inappropriate cesarean indications.KEY MESSAGESObstetricians/gynecologists are cautious to indicate a cesarean in pregnant patients with a previous myomectomy.Information to patients and among clinicians is crucial to avoid inappropriate cesarean indications in pregnant patients with a previous myomectomy.

Effect of expiratory flow limitation on ventilation/perfusion mismatch and perioperative lung function during pneumoperitoneum and Trendelenburg position.

BACKGROUND: Laparoscopic surgery and Trendelenburg position may affect the respiratory function and alter the gas exchange. Further the reduction of the lung volumes may contribute to the development of expiratory flow limitation (EFL). The latter is associated with an increased risk of postoperative pulmonary complications. Our aim was to investigate the incidence of EFL and to evaluate its effect on pulmonary function and intraoperative V/Q mismatch. METHODS: This is a prospective study on patients undergoing elective laparoscopic gynecological surgery. We evaluated respiratory mechanics, V/Q mismatch and presence of EFL after anesthesia induction, during pneumoperitoneum and Trendelenburg position and at the end of surgery. Intraoperative gas exchange and hemodynamic were also recorded. Clinical data were collected until seven days after surgery to evaluate the onset of pulmonary postoperative complications (PPCs). RESULTS: Among the 66 patients enrolled, 25/66 (38%) exhibited EFL during surgery, of whom 10/66 (15%) after anesthesia induction, and the remaining 15 patients after pneumoperitoneum and Trendelenburg position. Median PEEP able to reverse flow limitation was 7 [7-10] cmH2O after anesthesia induction and 9 [8-15] cmH2O after pneumoperitoneum and Trendelenburg position. Patients with EFL had significantly higher shunt (17 [2-25] vs. 9 [1-19]; P=0.05), low V̇/Q̇ (27 [20-70] vs. 15 [10-22]; P=0.05) and high V̇/Q̇ (10 [7-14] vs. 6 [4-7]; P=0.024). At the end of surgery, only high V/Q was significantly higher in EFL patients. Further, they exhibited higher incidence of postoperative pulmonary complication (48% (12/25) vs. 15% (6/41), P=0.005), hypoxemia and hypercapnia (80% [20/25] vs. 32% [13/41]; P<0.001). CONCLUSIONS: Expiratory flow limitation is a common phenomenon during gynecological laparoscopic surgery associated with worsen gas exchange, increased V/Q mismatch and altered lung mechanics. Our study showed that patients experiencing EFL during surgery showed a higher risk for PPCs.

Management of Patients Diagnosed with Endometrial Cancer: Comparison of Guidelines.

Endometrial cancer is the most common gynecological malignancy in Europe and its management involves a variety of health professionals. In recent years, big discoveries were made concerning the management of patients diagnosed with endometrial cancer, particularly in the field of molecular biology and minimally invasive surgery. This requires the continuous updating of guidelines and protocols over the years. In this paper, we aim to summarize and compare common points and disparities among protocols for management of patients diagnosed with endometrial cancer by leading international gynecological oncological societies. We therefore systematically report the parallel among the guidelines based on the various steps patients with endometrial cancer usually undergo. The comparison between American and European protocols revealed some relevant disparities, in particular regarding surgical staging, molecular biology application as a prognostic tool and follow up regimens. This could possibly cause differences in interpreting and applying protocols in clinical practice in small centers, leading to a lack of adherence to guidelines or even prompting a confusing mix of them.

Effect of SARS-CoV-2 infection in pregnancy on CD147, ACE2 and HLA-G expression.

INTRODUCTION: Recent studies reported a differential expression of both ACE2 and CD147 in pregnant women associated to SARS-CoV-2 placental infection. The aim of this study is to further investigate the placental SARS-CoV-2 infection and the potential effect on protein expression (ACE2, CD147, HLA-G and CD56). METHODS: The study was on three subgroups: i) 18 subjects positive for SARS-CoV-2 swab at delivery; ii) 9 subjects that had a positive SARS-CoV-2 swab during pregnancy but resulted negative at delivery; iii) 11 control subjects with physiological pregnancy and with no previous or concomitant SARS-CoV-2 swab positivity. None of the subjects were vaccinated for SARS-CoV-2 infection. The placenta samples were analyzed for SARS-CoV-2 NP (Nucleocapsid protein) positivity and the expression of ACE2, CD147, HLA-G and CD56. RESULTS: We observed a higher percentage of SARS-CoV-2 NP positive placenta samples in the group of SARS-CoV-2 PCR positive at delivery in comparison with SARS-CoV-2 PCR negative at delivery. The localization of SARS-CoV-2 NP positivity in placenta samples was mainly in syncytiotrophoblast (ST) of SARS-CoV-2 PCR positive at delivery group and in extra-villous trophoblast (EVT) of SARS-CoV-2 PCR negative at delivery group. CD147, HLA-G positivity was higher in ST of SARS-CoV-2 PCR positive at delivery group, while CD56-expressing immune cells were decreased in comparison with control subjects. DISCUSSION: We confirmed the ability of SARS-CoV-2 to infect placenta tissues. The simultaneous SARS-CoV-2 swab positivity at delivery and the positivity of the placenta tissue for SARS-CoV-2 NP seems to create an environment that modifies the expression of specific molecules, as CD147 and HLA-G. These data suggest a possible impact of SARS-CoV-2 infection during pregnancy, that might be worthy to be monitored also in vaccinated subjects.

Effectiveness and safety of COVID-19 vaccine in pregnant women: A systematic review with meta-analysis.

BACKGROUND: There are limited data regarding COVID-19 vaccination during pregnancy. OBJECTIVES: To evaluate the effects of COVID-19 vaccination received during pregnancy on SARS-CoV-2 infection, COVID-19-related hospitalisation, COVID-19-related intensive care unit (ICU) admission and maternal-fetal complications. SEARCH STRATEGY: MEDLINE, CINHAL, Embase, Scopus and CENTRAL databases, as well as ClinicalTrials.gov, reference lists, related articles and grey literature sources. SELECTION CRITERIA: Randomised controlled trials, non-randomised studies of interventions, pregnant women, COVID-19 vaccination during pregnancy. DATA COLLECTION AND ANALYSIS: Study selection, risk-of-bias assessment, data extraction and assessment of the certainty of evidence using the GRADE method were performed independently by two authors. Meta-analyses were performed using Cochrane RevMan 5.4. PROSPERO registration number: CRD42022308849. MAIN RESULTS: We included 14 observational studies (362 353 women). The administration of a COVID-19 vaccine during pregnancy resulted in a statistically significant reduction in SARS-CoV-2 infection (OR 0.46, 95% CI 0.28-0.76) and COVID-19-related hospitalisation (OR 0.41, 95% CI 0.33-0.51). The effect appeared to be greater in fully vaccinated women, for both infection (OR 0.31, 95% CI 0.16-0.59) and hospitalisation (OR 0.15, 95% CI 0.10-0.21). However, the certainty of evidence was very low. The difference in COVID-19-related ICU admission between vaccinated and unvaccinated individuals did not reach statistical significance (OR 0.58, 95% CI 0.13-2.58). Finally, there were no statistically significant differences in any of the maternal-fetal complications considered in the included studies. CONCLUSIONS: COVID-19 vaccination administered during pregnancy seems to reduce SARS-CoV-2 infection and COVID-19-related hospitalisation, with no significant effects on maternal-fetal complications.

Concurrent Endometrial Cancer in Women with Atypical Endometrial Hyperplasia: What Is the Predictive Value of Patient Characteristics?

BACKGROUND: The rate of concurrent endometrial cancer (EC) in atypical endometrial hyperplasia (AEH) can be as high as 40%. Some patient characteristics showed associations with this occurrence. However, their real predictive power with related validation has yet to be discovered. The present study aimed to assess the performance of various models based on patient characteristics in predicting EC in women with AEH. METHODS: This is a retrospective multi-institutional study including women with AEH undergoing definitive surgery. The women were divided according to the final histology (EC vs. no-EC). The available cases were divided into a training and validation set. Using k-fold cross-validation, we built many predictive models, including regressions and artificial neural networks (ANN). RESULTS: A total of 193/629 women (30.7%) showed EC at hysterectomy. A total of 26/193 (13.4%) women showed high-risk EC. Regression and ANN models showed a prediction performance with a mean area under the curve of 0.65 and 0.75 on the validation set, respectively. Among the best prediction models, the most recurrent patient characteristics were age, body mass index, Lynch syndrome, diabetes, and previous breast cancer. None of these independent variables showed associations with high-risk diseases in women with EC. CONCLUSIONS: Patient characteristics did not show satisfactory performance in predicting EC in AEH. Risk stratification in AEH based mainly on patient characteristics may be clinically unsuitable.

Corrigendum: Serum IgG antibodies from pregnant women reacting to mimotopes of Simian virus 40 large T antigen, the viral oncoprotein.

[This corrects the article DOI: 10.3389/fimmu.2017.00411.].

The Role of Melatonin in Pregnancy and the Health Benefits for the Newborn.

In the last few years, there have been significant evolutions in the understanding of the hormone melatonin in terms of its physiology, regulatory role, and potential utility in various domains of clinical medicine. Melatonin's properties include, among others, the regulation of mitochondrial function, anti-inflammatory, anti-oxidative and neuro-protective effects, sleep promotion and immune enhancement. As it is also bioavailable and has little or no toxicity, it has been proposed as safe and effective for the treatment of numerous diseases and to preserve human health. In this manuscript, we tried to evaluate the role of melatonin at the beginning of human life, in pregnancy, in the fetus and in newborns through newly published literature studies.