Exploring the Role of Mediterranean and Westernized Diets and Their Main Nutrients in the Modulation of Oxidative Stress in the Placenta: A Narrative Review.

Oxidative stress is a major cellular event that occurs in the placenta, fulfilling critical physiological roles in non-pathological pregnancies. However, exacerbated oxidative stress is a pivotal feature of different obstetric complications, like pre-eclampsia, fetal growth restriction, and other diseases. Compelling evidence supports the relevant role of diet during pregnancy, with pleiotropic consequences for maternal well-being. The present review aims to examine the complex background between oxidative stress and placental development and function in physiological conditions, also intending to understand the relationship between different dietary patterns and the human placenta, particularly how this could influence oxidative stress processes. The effects of Westernized diets (WDs) and high-fat diets (HFDs) rich in ultra-processed foods and different additives are compared with healthy patterns such as a Mediterranean diet (MedDiet) abundant in omega 3 polyunsaturated fatty acids, monounsaturated fatty acids, polyphenols, dietary fiber, and vitamins. Although multiple studies have focused on the role of specific nutrients, mostly in animal models and in vitro, further observational and intervention studies focusing on the placental structure and function in women with different dietary patterns should be conducted to understand the precise influence of diet on this organ.

Considering the Effects and Maternofoetal Implications of Vascular Disorders and the Umbilical Cord.

The umbilical cord is a critical anatomical structure connecting the placenta with the foetus, fulfilling multiple functions during pregnancy and hence influencing foetal development, programming and survival. Histologically, the umbilical cord is composed of three blood vessels: two arteries and one vein, integrated in a mucous connective tissue (Wharton's jelly) upholstered by a layer of amniotic coating. Vascular alterations in the umbilical cord or damage in this tissue because of other vascular disorders during pregnancy are worryingly related with detrimental maternofoetal consequences. In the present work, we will describe the main vascular alterations presented in the umbilical cord, both in the arteries (Single umbilical artery, hypoplastic umbilical artery or aneurysms in umbilical arteries) and the vein (Vascular thrombosis, aneurysms or varicose veins in the umbilical vein), together with other possible complications (Velamentous insertion, vasa praevia, hypercoiled or hypocoiled cord, angiomyxoma and haematomas). Likewise, the effect of the main obstetric vascular disorders like hypertensive disorders of pregnancy (specially pre-eclampsia) and chronic venous disease on the umbilical cord will also be summarized herein.

Patients with Invasive Lobular Carcinoma Show a Significant Increase in IRS-4 Expression Compared to Infiltrative Ductal Carcinoma-A Histopathological Study.

Background and Objectives: Breast cancer (BC) is the first diagnosed type of cancer and the second leading cause of cancer-related mortality in women. In addition, despite the improvement in treatment and survival in these patients, the global prevalence and incidence of this cancer are rising, and its mortality may be different according to the histological subtype. Invasive lobular carcinoma (ILC) is less common but entails a poorer prognosis than infiltrative ductal carcinoma (IDC), exhibiting a different clinical and histopathological profile. Deepening study on the molecular profile of both types of cancer may be of great aid to understand the carcinogenesis and progression of BC. In this sense, the aim of the present study was to explore the histological expression of Insulin receptor substrate 4 (IRS-4), cyclooxygenase 2 (COX-2), Cyclin D1 and retinoblastoma protein 1 (Rb1) in patients with ILC and IDC. Patients and Methods: Thus, breast tissue samples from 45 patients with ILC and from 45 subjects with IDC were analyzed in our study. Results: Interestingly, we observed that IRS-4, COX-2, Rb1 and Cyclin D1 were overexpressed in patients with ILC in comparison to IDC. Conclusions: These results may indicate a differential molecular profile between both types of tumors, which may explain the clinical differences among ILC and IDC. Further studies are warranted in order to shed light onto the molecular and translational implications of these components, also aiding to develop a possible targeted therapy to improve the clinical management of these patients.

Retrospective Analysis of Patients with Gynaecological Uterine Sarcomas in a Tertiary Hospital.

Uterine sarcomas are rare and heterogeneous malignancies accounting for 1% to 3% of all gynaecological tumours. There are many histological subtypes recognised, including leiomyosarcomas, endometrial stromal sarcoma, and uterine carcinosarcoma, although the latest has been recently discarded in this group. Despite its low incidence, these types of cancer currently entail multiple challenges, either in diagnostics or clinical management, with a poor prognosis associated. The present work aimed to complete a comparative analysis of the different histological subtypes based on the clinicopathological characteristics of our population, the therapeutic characteristics, and associated prognosis in 161 patients treated in our centre during the period between 1985 and 2020. Moreover, a systematic review grouped a total of 2211 patients with a diagnosis of uterine sarcoma from 19 articles published in 16 countries from 2002 to 2021 was performed, all with retrospective analyses. Our results showed that apart from uterine carcinosarcoma, leiomyosarcoma is the most frequent subtype of uterine sarcoma, with unique clinical, demographic, and survival parameters. To our knowledge, this is the first systematic review conducted in this field and, thus, it shows the difficulties of collecting a significant number of patients per year, a valid reason why multicentre or national registries are recommended to allow a more exhaustive analysis of this pathology.

Identification and characterization of endometrial carcinoma with tumor markers HE4 and CA125 in serum and endometrial tissue samples

Objective: Diagnosis of endometrial cancer (EC) is made by biopsy sampling with pathological analysis, but it is extremely important to make an accurate diagnosis in order to plan the specific treatment. We hypothesized that human epididymis protein 4 (HE4) in endometrial tissue and in serum could be beneficial for a more precise diagnosis. Material and Methods: This prospective study compared patients with EC against non- EC, matched through several variables. The inclusion criteria were: females older than 18 years who accepted to participate; who had never undergone surgery for other oncological pathologies (ovarian, colon, cervical carcinoma or uterine sarcoma); none of them had received preoperative chemo- or radio-therapy; and no participant had any severe renal or liver pathology. All had pre-surgery blood sampling and then underwent hysterectomy. Histopathological assessment of endometrial samples was made by a pathologist who compared normal histopathological staining with HE4-antibody staining. Results: In total there were 34 cases and 35 controls recruited. There was poor correlation between tissue HE4 in patients with and without carcinoma. However, serum HE4 was significant for the diagnosis of endometrial carcinoma (median EC: 123.1 U, median NE: 64.67 U, p=0.002), although the carbohydrate antigen 125 level was not significant (p=0.208). Conclusion: The findings concerning the utility of HE4 contrast with earlier reports. However, the conclusions for serum measurements are positive and suggest that the tumor marker HE4 seems to be able to diagnose EC.

An Updated Review of SARS-CoV-2 Vaccines and the Importance of Effective Vaccination Programs in Pandemic Times.

Since the worldwide COVID-19 pandemic was declared a year ago, the search for vaccines has become the top priority in order to restore normalcy after 2.5 million deaths worldwide, overloaded sanitary systems, and a huge economic burden. Vaccine development has represented a step towards the desired herd immunity in a short period of time, owing to a high level of investment, the focus of researchers, and the urge for the authorization of the faster administration of vaccines. Nevertheless, this objective may only be achieved by pursuing effective strategies and policies in various countries worldwide. In the present review, some aspects involved in accomplishing a successful vaccination program are addressed, in addition to the importance of vaccination in a pandemic in the face of unwillingness, conspiracy theories, or a lack of information among the public. Moreover, we provide some updated points related to the landscape of the clinical development of vaccine candidates, specifically, the top five vaccines that are already being assessed in Phase IV clinical trials (BNT162b2, mRNA-1273, AZD1222, Ad26.COV2.S, and CoronaVac).

Cytokine profile during pregnancy predicts relapses during pregnancy and postpartum in multiple sclerosis.

OBJECTIVE: To explore the serum cytokine profile associated with disease activity during pregnancy and postpartum in MS, and to assess any potential biomarkers predicting the occurrence of relapses during this period. METHODS: We included 53 MS pregnant women recruited between 2007 and 2018. Interferon-gamma, Tumor necrosis factor-alpha, interleukin-17, granulocyte/macrophage-colony stimulating factor, Activin-A, interleukin-10, and programmed-death-ligand-1 (PD-L1) were measured quarterly in serum by ELISA. RESULTS: Seventeen patients (32%) experienced relapses during pregnancy or puerperium and 37(68%) did not. We did not found differences in clinical characteristics or treatment status between the two groups. However, relapsing patients showed at the first trimester of pregnancy considerably lower levels of serum Activin-A (336.4 pg/dl [289.6-491.7], median [IQR] vs. 760.0 pg/dl [493.2-1108.0],p = .003), which correlated positively with serum PD-L1 (r = 0.53,p = .0005) and IL-10 (r = 0.43,p = .004) values. Activin-A levels lower than 515 pg/ml at the first trimester identified patients with high probability of relapsing during pregnancy and postpartum (OR = 13.75, CI: 2.5-76.8, p = .001). CONCLUSIONS: MS patients with no relapses during pregnancy and puerperium showed an early triggering of a tolerogenic innate immune response evidenced by high serum Activin-A concentrations during the first trimester of pregnancy. Thus, serum Activin-A can be a useful biomarker to predict clinical activity during this period.

Prenatal diagnosis of pericallosal lipoma: Systematic review.

The aim is to present a systematic review of all the published cases of prenatally diagnosed pericallosal lipomas, their features and associations with other anomalies or syndromes and their post-natal evolution. We performed a Pubmed-based systematic review, including all the published cases of prenatal diagnosis of pericallosal lipoma, written in English, Spanish or French. We analysed gestational age at diagnosis, prenatal ultrasound characteristics of the lipoma, prenatally diagnosed associated anomalies, neonatal findings, outcomes and duration of follow-up. We gathered data from 49 cases of prenatally diagnosed pericallosal lipoma. Mean gestational age at diagnosis was 29.6 weeks. The type of lipoma was: not specified in 8 cases, tubulonodular in 17 cases, curvilinear in 24 cases. Corpus callosum was hypoplastic in 19 cases of curvilinear lipomas (79.2%) and 3 cases of tubulonodular lipomas (17.6%) (p < 0.001). There was agenesis (partial or complete) of corpus callosum in 76.5% of the cases of tubulonodular lipoma and 8.3% of the cases of curvilinear lipoma (p < 0.001). There were three cases of Pai syndrome, and three cases of Goldenhar syndrome. Mean post-natal follow-up was 36.3 months. Neurological evaluation was normal in 92.1% of the cases (75% of the tubulonodular lipoma, 100% of the curvilinear lipoma, p < 0.05). Tubulonodular lipomas present a higher frequency of associated neurological anomalies. A thorough study of the lipoma and a search of associated anomalies is paramount. Parental counselling should take into account this classification and associated findings as the prognosis varies widely. Further studies with longer follow-up are necessary to increase our knowledge.

Breast cancer during pregnancy: results of maternal and perinatal outcomes in a single institution and systematic review of the literature.

To compare the maternal and the perinatal variables of the patients with pregnancy associated breast cancer (PABC) and the pregnant patients without breast cancer (PNABC), we retrospectively included 13 PABC cases and 66.265 PNABC patients. The PABC patients presented a lower mean gestational age at their delivery and had higher induction of labour and prematurity rates. A diagnosis was performed before stage III in 77% of the cases. The overall survival was 90%; moreover, we collected 16 manuscripts when gathering data from 1581 patients with PABC. The mean follow-up time was 70 ± 8 months. The mean maternal age at diagnosis was 34 years old. Most of the patients were at their second trimester of pregnancy. The gestational age at delivery was 35 weeks. A mastectomy was the most frequently used surgical approach. PABC should be managed by a multidisciplinary team, ensuring there is a rigorous oncological treatment, with foetal well-being. IMPACT STATEMENT What is already known on this subject? The malignant breast tumours diagnosed during pregnancy, or 1 year after a delivery are increasing, there is evidence supporting the treatment during a pregnancy with maternal and foetal safety. A PABC should be managed by a multidisciplinary team in a referral centre, ensuring that there is a rigorous oncological treatment with foetal well-being. What do the results of this study add? Our results show that the PABC patients in our centre had a mean maternal age older than the PNABC women, as well as a higher percentage of the induction of labour and prematurity. 48 Cancer was usually diagnosed in early stages, and the most common type was ductal infiltrating, with positive hormonal receptors. For those patients continuing their pregnancies, a mastectomy plus a lymphadenectomy was the most frequent chemotherapy, and was usually administered in the third trimester of pregnancy. What are the implications of these findings for future clinical practice and/or further research? Moreover, the number of publications concerning PABC has grown, series are still scarce. We understand the limitations of the low number of the cases on our population, but this study is the first which compare the PABC with the PNABC patients, allowing to describe and compare the obstetrical and perinatal variables. Finally, we consider it is of a paramount importance to create an international database to register in a prospective way all of the cases of PABC to increase our knowledge in this field.

Maternal and perinatal outcomes in pregnancy-associated melanoma. Report of two cases and a systematic literature review.

OBJETIVES: Melanoma is one of the most frequent malignancies during gestation. However, oncological and perinatal management is still challenging. Our first objective is to describe the cases of pregnancy-associated melanoma (PAM) diagnosed in our centre between January-2004 and May-2015. Secondly, to perform a systematic review of the published articles analysing the maternal-perinatal outcomes of patients diagnosed with PAM. DESIGN, POPULATION AND METHODS: Obstetrical, oncological and perinatal variables were recorded in the case series. For the systematic review we include all published articles assessing the obstetric and neonatal outcomes in PAM cases in Pubmed, Web of Knowledge and Cochrane Library. The search was restricted to articles published in English, between January-2004 and May-2015. Study characteristics, oncological and maternal-perinatal variables were recorded in the systematic review. RESULTS: Two patients were found: the first case presents a newly diagnosed metastatic melanoma at 26-weeks of gestation with fatal maternal and neonatal outcome. The second case presents a patient with metastatic melanoma who got pregnant during her treatment. For the systematic review we found 25 articles, providing data from 489 patients. Maternal-perinatal outcomes, including termination of pregnancy rates, vary depending on the country, gestational age and tumour stage at diagnosis. PAM is usually detected at advanced stages, even with metastasis affecting the placenta and the foetus. CONCLUSIONS: When diagnosed at early stages, melanoma does not seem to alter the evolution of gestation, whereas patients with advanced stages of melanoma frequently deliver prematurely, by caesarean section, with lower neonatal weight, higher neonatal morbidity and mortality rates.

Prenatal Diagnosis of an Aortopulmonary Window With an Interrupted Aortic Arch.

A prenatal aortopulmonary window with an interrupted aortic arch was detected in a 22-week-old fetus. The 3-vessel and trachea view showed a communication between the ascending aorta and the pulmonary artery. Early postnatal surgery was successful. A PubMed-based search identified all cases of prenatal aortopulmonary windows between 2002 and 2015. Nine articles were identified. The average gestational age at diagnosis was 28 weeks (range, 22-33 weeks). The most frequent aortopulmonary window was type I (40%). All cases were associated with congenital heart defects, mainly an interrupted aortic arch (50%). No chromosomal or extracardiac abnormalities were seen. Prenatal echocardiography is useful for early diagnosis of an aortopulmonary window. The prognosis depends on the time of surgery and the nature of the associated anomalies.

Neonatal magnetic resonance imaging in double aortic arch diagnosed prenatally by ultrasound.

Congenital double aortic arch (DAA) is an uncommon vascular anomaly; however, its prenatal detection is associated with congenital heart defects and chromosomal abnormalities, including 22q11 deletion. We present a case of DAA diagnosed prenatally. DAA can be diagnosed by prenatal ultrasound in the transverse three vessel-trachea view, which shows a trident image formed by a complete vascular ring and the ductus arteriosus. Postnatal magnetic resonance images in this view correlate well with prenatal ultrasound images and help in confirmation of diagnosis, evaluation of the risk of airway or esophageal compression, and planning of surgery.

[Prenatal diagnosis of fetal aortic stenosis with mitral insufficiency. Review of the ultrasound diagnosis and perinatal prognosis: a case report]. / Diagnóstico prenatal de la estenosis aórtica crítica con insuficiencia mitral. Revisión del diagnóstico ecográfico y pronóstico perinatal. A propósito de un caso.

This is a report about a case of prenatal diagnosis of critical fetal aortic stenosis with severe mitral valve insufficiency in a 35+6 weeks fetus. Aortic stenosis represents 3% of congenital heart diseases, but its association with mitral regurgitation is quite unusual. Thanks to the latest advances in fetal ultrasonography we can now achieve a more precise diagnosis and we have been able to improve the understanding of its physiopathology. Based on this case we have reviewed the most recent literature about fetal aortic stenosis and mitral valve insufficiency, with the aim of summarizing its main physiopathological features, highlighting the clues and key points for its intrauterine diagnosis, describing its principal complications and summarizing its current treatment options.

[Prenatal ultrasonic diagnosis and follow-up of fetal splenic cysts: report of two cases. Review of the literature]. / Diagnóstico ecográfico prenatal y seguimiento de quistes esplénicos fetales: a propósito de dos casos. Revisión de la bibliografía.

Congenital splenic cysts are rare entities wich are not frequently diagnosed in prenatal sonographies and there is only a few literature wich report these medical cases. The aim of this article is to introduce this sonographic discovery and study whether there are impacts for the newborn, association with cormosomopathy or fetal pathology. We describe two medical cases of fetal splenic cysts wich were diagnosed in our service by ultrasonography at 29 and 32 weeks of gestation, their antenatal monitoring and postnatal evolution. Besides theses, it is made a review of this entity in medical literature, examination about the: etiology, prenatal diagnosis, prenatal and postnatal following and complications. In conclusion, the congenital splenic cyst has a good prognosis with an spontaneous postnatal resolution in the majority of the cases. No association was observed between cromosopathy or fetal pathology with the examined cases.

[Laparoscopic management of a spontaneous live monochorionic monoamniotic twin tubal ectopic pregnancy. A case report]. / Tratamiento laparoscópico de una gestación ectópica tubárica gemelar monocorial monoamniótica espontánea. Caso clínico.

We present a case of a spontaneous live monochorionic monoamniotic twin tubal ectopic pregnancy detected by transvaginal ultrasound scan after medical therapy with single dose of methotrexate failed. The incidence of this type of ectopic pregnancies is probably arising due to the increasing use of the assisted reproduction techniques, but they are underdiagnosed and mistreated, as surgical approach seems to be the most adequate in these cases.

Second trimester amniotic fluid adiponectin level is affected by maternal tobacco exposure, insulin, and PAPP-A level.

OBJECTIVES: Adiponectin is an adipocyte-derived plasma protein with insulin-sensitizing and antiatherosclerotic properties. The objectives of the present study were to determine the amniotic fluid (AF) concentration of adiponectin during the second trimester of pregnancy and to demonstrate its association with maternal and fetal variables and AF concentrations of insulin, leptin, and pregnancy-associated-plasma-protein A (PAPP-A). STUDY DESIGN: We performed a cross-sectional study of 222 pregnant women who underwent amniocentesis at 15-18 weeks for genetic reasons. No malformation or chromosomal disorder was found in the newborn after birth. AF adiponectin, leptin, PAPP-A, and insulin concentrations were measured using commercially available assays. All maternal, fetal, and biochemical variables were studied using univariate and multivariate linear regression analysis to determine their association with the AF concentration of adiponectin. RESULTS: Adiponectin concentration was negatively correlated with maternal smoking status (ß=-5.208; p<0.001) and positively correlated with levels of insulin (ß=0.621; p=0.002) and PAPP-A (ß=40.150; p<0.001). Non-significant correlations were found between adiponectin concentration and maternal age, maternal body mass index, gestational age at amniocentesis, fetal gender, and AF level of leptin. CONCLUSION: These findings suggest that the fetus and its membrane adipocytokines, in relationship with maternal and other fetal variables, play a dynamic role in the regulation of energy and oxidative stress homeostasis due to its insulin-sensitizing and antiatherosclerotic effects. The association of these molecules with maternal tobacco consumption during pregnancy could have perinatal implications.

Candidate biomarkers for acute rejection of pregnancy after in-utero cell-based therapy in pre-immune embryos via ultrasound-guided celocentesis.

PROBLEM: A maternal serum biomarker profile analysis was performed to determine potential indicators of acute rejection of pregnancy following in-utero cell-based treatments in pre-immune embryos. METHOD OF STUDY: We used an established non-human primate model for in-utero stem cell therapy at 38-42 days from fertilization. The maternal serum concentrations of nine candidate biomarkers for acute rejection of pregnancy were determined before and after the injection of different cocktails of human umbilical cord blood stem cells into the gestational sac. All animals were then followed until delivery. RESULTS: Twenty-four hours after celocentesis, two of the animals aborted. These two animals received a cocktail of haemopoietic stem cells with the highest concentration of human CD3(+) cells and showed a twofold increase in maternal serum IL-6 and a threefold increase in prolactin after the procedure. The remaining six animals delivered at term live and normal newborns and only demonstrated an increase in prolactin after the celocentesis procedure. CONCLUSION: IL-6 and prolactin are master immunoregulators with pleiotropic biological functions that have different maternal serum concentrations depending on pregnancy outcome. These findings suggest that increases in maternal serum prolactin and IL-6 concentration may be associated with acute rejection of pregnancy after in-utero stem cell therapy.

[Fetal ovarian cyst: prenatal diagnosis, perinatal outcome and treatment. Case series and literature review]. / Quiste de ovario fetal: diagnóstico prenatal, evolución perinatal y tratamiento. Serie de casos y revisión de la bibliografía.

BACKGROUND: Ovarian cysts in fetal abdominal tumors are more frequently diagnosed during pregnancy. Most of the time are usually small, asymptomatic and resolve spontaneously during pregnancy or in early neonatal life. OBJECTIVE: To describe the clinical and ultrasound cases with prenatal diagnosis of ovarian cyst treated in our center between 2002 and 2005. MATERIAL AND METHODS: Descriptive and observational cases of fetal ovarian cyst diagnosedbefore birth. The variables maternal and perinatal most relevant clinical data obtained at diagnosis and after birth. RESULTS: We explored 9.198 fetuses, of which there were 10 cases of ovarian cyst diagnosed between the second and third trimesters of pregnancy. All cases were unilateral andsonographic appearance homogeneous. In four cases there was spontaneous disappearance during the remaining gestational period. In the other six cases, four missing in the first 12 months and only two image persisted more than a year. CONCLUSIONS: Based on our results and in accordance with the literature, the prenatal diagnosis of fetal ovarian cyst is usually associated with a conservative approach with serialultrasound monitoring to rule out rare serious complications. During the neonatal period spontaneous disappearance is often the case and the surgical approach is indicated in cases with suspected persistent or torsion or hemorrhage, with cystectomy as first choice.