Biomarkers for Early Prediction and Management of Preeclampsia: A Comprehensive Review.

Preeclampsia is a common complication of pregnancy. It is a multi-organ disorder that remains one of the main causes of maternal morbidity and mortality. Additionally, preeclampsia leads to many complications that can occur in the fetus or newborn. Preeclampsia occurs in about 1 in 20 pregnant women. This review focuses on the prediction of preeclampsia in women, using various biomarkers, in particular, a factor combining the use of soluble FMS-like tyrosinokinase-1 (sFlt-1) and placental growth factor (PlGF). A low value of the sFlt-1/PlGF ratio rules out the occurrence of preeclampsia within 4 weeks of the test result, and its high value predicts the occurrence of preeclampsia within even 1 week. The review also highlights other factors, such as pregnancy-associated plasma protein A, placental protein 13, disintegrin and metalloprotease 12, ß-human chorionic gonadotropin, inhibin-A, soluble endoglin, nitric oxide, and growth differentiation factor 15. Biomarker testing offers reliable and cost-effective screening methods for early detection, prognosis, and monitoring of preeclampsia. Early diagnosis in groups of women at high risk for preeclampsia allows for quick intervention, preventing the undesirable effects of preeclampsia. However, further research is needed to validate and optimize the use of biomarkers for more accurate prediction and diagnosis. This article aims to review the role of biomarkers, including the sFlt1/PlGF ratio, in the prognosis and management of preeclampsia.

The Influence of Gestational Diabetes Mellitus on Maternal and Neonatal Outcomes: A Retrospective Study in Rzeszów, Poland.

BACKGROUND Gestational diabetes mellitus (GDM) affects 5.8-12.9% of pregnant women, while pre-gestational diabetes mellitus (PGDM) affects 0.4-1.1%. GDM increases the risk of perinatal complications and long-term health issues. This retrospective study from a single centre in Rzeszów, Poland aimed to evaluate maternal and neonatal outcomes of pregnancy of 65 women with gestational diabetes mellitus. MATERIAL AND METHODS The study group consisted 65 women with GDM. The control group consisted 60 women without. GDM were diagnosed with carbohydrate metabolism disorders during pregnancy based on the results of the oral glucose tolerance test (OGTT). Methods of evaluation of the mothers: age, body mass before pregnancy, body height, body mass index (BMI), gravidity, parity, the number of miscarriages, length of stay (LOS) of mother, gestational weight gain (GWG), duration of pregnancy, type of delivery, treatment of diabetes. Methods of evaluation of the child: LOS, birth weight, Apgar points. RESULTS Women with diabetes stayed in hospital longer than women without, similarly applies the length of stay (LOS) of the child (p<0.001). It turned out that the women with GDM were significantly more likely to deliver by caesarean section (CS) (p=0.024) and these women most often had gestational weight gain (GWG) within the recommended range (p<0.001). Body mass index (BMI) before pregnancy was significantly higher in the women with GDM (p=0.023). CONCLUSIONS The above study confirms that the occurrence of GDM has an undoubted impact on prolonged LOS of the mother and child, more frequent CS delivery and normal GWG.

Evaluation of miRNA Expression in Patients with Gestational Diabetes Mellitus: Investigating Diagnostic Potential and Clinical Implications.

Purpose: Gestational diabetes mellitus (GDM) is common pregnancy complication (8%), characterized by hyperglycemia resulting from pathological homeostatic mechanisms. There's a concerning trend of increasing GDM prevalence. New markers, particularly epigenetic ones, are sought for early detection and enhanced care. miRNA are small non-coding RNA molecules. The main goal was to investigate the potential role of miRNA (miR-16-5p, miR-222-3p, miR-21-5p) in GDM and their association with clinical features. Patients and Methods: The study included 72 pregnant patients, with 42 having GDM and 30 in the control group. miRNA expression was measured using ELISA. Results: There were no significant differences in miR-222-3p expression between GDM patients and the control group. The GDM group exhibited a positive correlation between miR-16-5p expression and miR-21-5p expression as well as between miR-16-5p expression and insulin resistance. In the GDM group, a positive correlation was observed between miR-21-5p expression and fasting glucose levels. Conclusion: Results do not confirm the role of miR-222-3p in GDM pathogenesis or as a diagnostic marker. Additionally, a role for miR-16-5p in GDM pathogenesis was observed. Furthermore, a potential role for miR-21-5p in monitoring GDM treatment is indicated.

Intrauterine deaths - an unsolved problem in Polish perinatology.

OBJECTIVES: The Polish criteria for "intrauterine death" include fetal demise after 22 weeks of gestation, weighing > 500 g and body length at least 25 cm, when the gestational age is unknown. The rate of fetal death in Poland in 2015 is 3:10,000. In 2020, 1,231 stillbirths were registered. MATERIAL AND METHODS: An analysis using 142,662 births in the period between 2015-2020 in 11 living in Poland. The first subgroup was admitted as patients > 22 to the beginning of the 30th week of pregnancy (n = 229), and the second from the 30th week of pregnancy inclusively (n = 179). In the case of women from both subgroups, there was a risk of preterm delivery close to hospitalization. RESULTS: It was found that stillbirth in 41% of women in the first pregnancy. For the patient, stillbirth was also the first in his life. The average stillbirth weight was 1487 g, the average body length was 40 cm. Among fetuses up to 30 weeks, male fetuses are born more often, in subgroup II, the sex of the child was usually female. Most fetal deaths occur in mothers < 15 and > 45 years of age. CONCLUSIONS: According to the Polish results of the origin of full-term fetuses > 30 weeks of gestation for death in the concomitant antenatal, such as placental-umbilical and fetal hypoxia, acute intrapartum effects rarely, and moreover < 30 Hbd fetal growth restriction (FGR), occurring placental-umbilical, acute intrapartum often.

Contained Power Morcellation in Laparoscopic Uterine Myoma Surgeries: A Brief Review.

Uterine fibromas are the most common benign uterine tumors. Although the majority of leiomyomas remain asymptomatic, they can cause serious clinical problems, including abnormal uterine bleeding, pelvic pain, and infertility, which require effective gynecological intervention. Depending on the symptoms as well as patients' preferences, various treatment options are available, such as medical therapy, non-invasive procedures, and surgical methods. Regardless of the extent of the surgery, the preferred option is the laparoscopic approach. To reduce the risk of spreading occult malignancy and myometrial cells associated with fragmentation of the specimen before its removal from the peritoneal cavity, special systems for laparoscopic contained morcellation have been developed. The aim of this review is to present the state-of-the-art contained morcellation. Different types of available retrieval bags are demonstrated. The advantages and difficulties associated with contained morcellation are described. The impact of retrieval bag usage on the course of surgery, as well as the effects of the learning curve, are discussed. The role of contained morcellation in the overall strategy to optimize patient safety is highlighted.

The Diagnostics and Treatment of Recurrent Pregnancy Loss.

Recurrent pregnancy loss is a common problem in the reproductive age population of women. It can be caused by many different conditions. This problem is addressed in international guidelines that take a slightly different approach to its diagnosis and treatment. The guidelines used in this review mainly use the guidelines of the Royal College of Obstetricians and Gynaecologists (RCOG), American Society of Reproductive Medicine (ASRM) and European Society of Human Reproduction and Embryology (ESHRE). This review shows how much the approach to miscarriages has changed and how much more needs to be explored and refined. The review also addresses the topic of unexplained pregnancy loss, which continues to be a challenge for clinicians.

Factors affecting self-esteem and disease acceptance in patients from infertile couples.

Introduction: Infertility has been diagnosed in millions of people around the world and is described as a complex medical, mental, and social problem that affects many aspects of life. The aim of the study was to extract the determining factors and the level of self-esteem and the degree of acceptance of the disease in infertile patients and to find differences between women and men in this aspect. Methods: A total 456 patients (235 women and 221 men) from infertile couples participated in a cross-sectional study. To collect data a Personal Information Form (PIF), Rosenberg Self-Esteem Scale (SES), and Acceptance of Illness Scale (AIS) were used. Results: The overall self-esteem score for the whole sample was 30.50 (15 ± 30) points and for acceptance of the disease 32.4 (8 ± 40) points. In the study group, men obtained a slightly higher level of self-esteem than women (31.00 vs. 30.04 points). Additionally, men had a higher level of acceptance of the disease (33.12 vs. 31.80) than women. Socio-demographic factors such as age and level of education had impact on scores SES and AIS. Clinical factors did not determine the results of SES and AIS, both in the overall sample and in the female and male groups. Conclusion: Self-esteem in patients from infertile couples increases with age and level of education. There are also significant differences between women and men, i.e., positive correlations between the level of education and self-esteem in men and the degree of acceptance of the disease in women.

Plasma Circular-RNA 0005567 as a Potential Marker of Disease Activity in Rheumatoid Arthritis.

Circular RNAs (circRNAs) are noncoding molecules and are generated through back splicing, during which the 5' and 3' ends are covalently joined. Consequently, the lack of free ends makes them stable and resistant to exonucleases, and they become more suitable biomarkers than other noncoding RNAs. The aim of the study was to find an association between selected circRNAs and disease activity in patients with RA. A total of 71 subjects, 45 patients with RA and 26 healthy controls (HCs), were enrolled. In the RA group, 24 patients had high disease activity (DAS-28-ESR > 5.1) and 21 individuals were in remission (DAS-28-ESR ≤ 2.6). The cell line SW982 was used to evaluate the biological function of circ_0005567. The concentration of circ_0005567 in RA patients was elevated compared to HCs (median, 177.5 [lower-upper quartile, 83.13-234.6] vs. 97.83 [42.03-145.4], p = 0.017). Patients with high disease activity had a higher concentration of circ_0005567 than the control group (185.4 [112.72-249.25] vs. 97.83 [42.03-145.4], p = 0.015). In the cell line model, we found an association between circ_0005567 and miR-194-5p concentration and increased expression of mRNAs that may be related to cell proliferation. The plasma concentration of circ_0005567 may be a new potential biomarker associated with disease activity in patients with RA.

Health Related Behaviors and Life Satisfaction in Patients Undergoing Infertility Treatment.

The aim of the study was to evaluate the level of life satisfaction and health behaviors presented by patients with diagnosed infertility. This cross-sectional study included 456 patients (235 women and 221 men) from infertile couples in southeastern Poland from June 2019 to February 2020. Participants completed a questionnaire on sociodemographic characteristics, the Health Behaviors Inventory (HBI), and the Satisfaction with Life Scale (SWLS). The average score of severity of health behaviors for the study group was 82.96 points. Satisfaction with life at a higher level was declared by 57.6% of respondents, at an average level was declared by 31.4%, and at a lower level was declared by 11%. The SWLS score for the entire study group was 24.11 points (6.82 points on the sten scale). Respondents who achieved a higher rate of life satisfaction also had a higher level of severity of health behaviors (p < 0.0001). There were no significant differences between male and female SWLS scores, although the women had significantly higher rates of severity of health behaviors than men. The level of health behavior is positively related to life satisfaction in infertile patients. Medical personnel should conduct health education on a healthy lifestyle that promotes the improvement of reproductive health.

The lack of association between PADI4_94 or PADI4_104 polymorphisms and RF, ACPA and anti-PAD4 in patients with rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronic autoimmune disease that leads to chronic inflammation of synovial tissue, ultimately causing joint damage, disability, and premature mortality. The peptidylarginine deiminase (PAD) family of proteins is involved in the production of anticitrullinated peptide antibodies (ACPA), which are clinically relevant markers of RA. ACPA recognizes citrullinated proteins generated mainly by PAD4. Polymorphisms of the PADI4 gene have been associated with RA in Asian populations, but in Europeans these associations are still difficult to estimate. A total of 147 subjects, 122 patients with RA, 52 ± 12.3 aged, 84.4% women and 25 healthy controls, 53 ± 8.4 aged, 72% women were enrolled in the study. Two single nucleotide polymorphisms (SNPs) of the PADI4 gene (PADI4_94, rs2240340 and PADI4_104, rs1748033) were genotyped using a real-time polymerase chain reaction. Genetic models (co-dominant-1 and 2, dominant, over-dominant, and recessive) were applied to find the associations between genotypes and ACPA as well as PAD4 antibodies (anti-PAD4) levels. We found no relationship between the distribution of genotypes in different genetic models and the levels of anti-PAD4, ACPA and RF antibodies. There were also no differences with respect to the haplotypes. Genetic variants PADI4_94 and PADI4_104 may not be clinically relevant as prognostic factors in patients with established RA.

Laparoscopic in-bag morcellation - a comparison of two tissue extraction systems.

OBJECTIVES: Morcellation is an integral part of laparoscopic procedures related to uterine fibroids, which consist of the mechanical fragmentation of the tumor and its extraction outside the abdominal cavity. To avoid the risk of tissue dissemination, special extraction systems have been developed, which allow morcellation of the specimen under visual control and its removal without contact with the abdominal organs. The aim of the paper is to compare the two systems for laparoscopic morcellation. MATERIAL AND METHODS: The study included 33 premenopausal women with symptomatic leiomyomas or adenomyosis, who were qualified for laparoscopic surgery with contained power morcellation. Patients were allocated alternately to a different tissue extraction system's group. According to the study protocol, selected operative parameters were prospectively recorded. Finally, an assessment of bag use was performed. The data was statistically analyzed. RESULTS: There were significant differences between the two tested systems in terms of introducing and positioning the bag, its removal from the peritoneal cavity, as well as optic trocar insertion and establishing the pseudo-peritoneum. CONCLUSIONS: Despite the minor design differences and some ergonomic aspects, both presented systems proved to be safe and feasible tools for laparoscopic contained morcellation. This technique both reduces the risk of tissue dissemination and preserves the advantages of minimal invasiveness.

Approach of Pregnant Women from Poland and the Ukraine to COVID-19 Vaccination-The Role of Medical Consultation.

There are many arguments for the safety and efficacy of COVID-19 vaccines in pregnancy. The aim of this study is to describe the level of vaccination acceptance, to find the factors that most influence the decision to vaccinate, and to describe the scale of changes in vaccination acceptance influenced by medical information on the safety, efficacy, and benefits of vaccination among pregnant women. A total of 300 patients completed the questionnaire, including 150 in Poland and 150 in the Ukraine. The level of vaccination acceptance was assessed before and after medical consultation. There were 53 (35.3%) patients with the intention to get vaccinated in Poland and 25 (16.7%) in the Ukraine. After consultation with a physician, this increased to 109 (72.6%) in Poland and 69 (46%) in the Ukraine. The main factors influencing the acceptance of vaccinations were the fear of harming the foetus (OR-0.119, CI-0.039-0.324 p < 0.001), complications in pregnancy (OR-0.073 CI-0.023-0.197 p < 0.001), and limitations in the vaccination programme (OR-0.026 CI-0.001-0.207 p < 0.001). Medical information about the safety, effectiveness and benefits of vaccinations among pregnant women, provided during a medical visit, may increase the acceptance of vaccinations by 105.6%, as among Polish patients, and by 176%, as among pregnant women from the Ukraine.

A Multi-Center, Randomised, Double-Blind, Placebo-Controlled Phase III Clinical Trial Evaluating the Impact of BCG Re-Vaccination on the Incidence and Severity of SARS-CoV-2 Infections among Symptomatic Healthcare Professionals during the COVID-19 Pandemic in Poland-First Results.

Tuberculosis vaccines (Bacillus Calmette-Guérin, BCG) were introduced 100 years ago and are still recommended by the World Health Organization to prevent the disease. Studies have shown that BCG vaccination can stimulate non-specific immune responses and reduce the incidence of certain diseases. At the beginning of the coronavirus disease 2019 (COVID-19) pandemic, it was hypothesised that the incidence of COVID-19 was lower in countries with BCG prevention. In an attempt to verify this thesis, we conducted a multicenter, randomised, double-blind, placebo-controlled study on a group of 695 health care workers aged 25 years and over in Poland. All participants in the study had a tuberculin test, after which those who were negative were randomised (1:1) and received either the BCG- or placebo vaccine. From then on, these people were subjected to three months of observation for the occurrence of COVID-19 symptoms. The statistical analysis did not reveal any significant correlation between the frequency of incidents suspected of COVID-19 and BCG-10 vaccination, the result of the tuberculin test and the number of scars. The only statistically significant feature was the type of medical profession-nurses became infected more often than doctors or other medical workers (p = 0.02). The results differ from similar trials in other countries. Perhaps this is due to the lack of an unvaccinated control group. The impact of BCG vaccination on the course of COVID-19 requires further research.

Epigenetic Links between Microbiota and Gestational Diabetes.

Gestational diabetes mellitus (GDM) is considered a significant and increasing worldwide problem. The growing body of evidence on this topic has allowed us to point out that a hostile intrauterine environment in mothers with GDM via epigenetic mechanisms induces "diabetogenic" and "obesogenic" changes in an offspring's DNA. This sets a vicious intergenerational cycle of metabolic diseases in motion, gradually deteriorating the health of the human population. One of the most important participants of this process seems to be altered microbiota. There is a chance that the identification of specific epigenetic marks may provide a key for future diagnostic, prognostic and therapeutic solutions in the field of personalised medicine. Given the reversibility of most epigenetic changes, there is an opportunity to improve the long-term health of the human population. In this manuscript, we aim to summarise available data on epigenetic changes among women suffering from GDM and their progeny, in association with alterations in the microbiome.

Plasma micro-RNA-22 is associated with disease activity in well-established rheumatoid arthritis.

OBJECTIVES: Micro-RNAs (miRNAs) are an endogenous small, single-stranded, non-coding RNAs with a 18-25 nucleotide long and have been reported as potential extracellular biomarkers of various diseases. They mainly decrease the gene expression by inhibiting the translation or cause mRNA destabilisation. The aim of our study was to identify miRNAs whose concentration may be associated with severity of rheumatoid arthritis (RA). METHODS: A total of 74 unrelated individuals, 50 with RA and 24 in a control group were enrolled to the study. Real-time PCR was used to evaluate the plasma concentration levels of 8 miRNAs: miR-26a, miR-125b, miR-20b, miR-22, miR-221, miR-17, miR-93, miR-106b. RESULTS: The logistic regression results showed that miR-22 (p=0.0003) and miR-26a (p=0.049) may be the most important molecules distinguishing RA patients and healthy controls. Moreover, the quantity of miR-22 was different between rheumatoid factor (RF)-positive and RF-negative patients (p=0.04). CONCLUSIONS: In this study we demonstrated for the first time that plasma concentration of miR-22 may be considered as a potential molecular marker associated with disease activity.

A Multi-Centre, Randomised, Double-Blind, Placebo-Controlled Phase III Clinical Trial Evaluating the Impact of BCG Re-Vaccination on the Incidence and Severity of SARS-CoV-2 Infections among Symptomatic Healthcare Professionals during the COVID-19 Pandemic in Poland-Evaluation of Antibody Concentrations.

Tuberculosis (TB) was the predominant cause of death from a single infectious agent worldwide before the severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) pandemic. Although TB vaccines have been successfully used for about 100 years, their full effect is still unknown. In previous studies, a reduced incidence and mortality from a coronavirus disease in TB-vaccinated populations were reported. In this article, we present the secondary analysis of a randomised controlled trial, reporting the results of a serological assessment evaluating the effect of the Bacillus Calmette-Guérin (BCG) vaccine on SARS-CoV-2. Participants-healthcare workers-were assessed 1-2 and 8 months after the second dose of the coronavirus disease 2019 (COVID-19) vaccine. We found no associations between antibody concentration, BCG revaccination, and additional characteristics, such as age, gender, or Body Mass Index. The effect of BCG vaccination on the immunological response against SARS-CoV-2 requires further research.

The Association of IL-17 and PlGF/sENG Ratio in Pre-Eclampsia and Adverse Pregnancy Outcomes.

The aim of the study was to assess the role of concentrations of interleukin-17 (IL-17), placental growth factor (PlGF) and soluble endoglin (sENG), as well as the PlGF/sENG ratio in pregnancy complicated by pre-eclampsia (PE) and normal pregnancy. The concentrations of IL-17, PlGF and sENG were measured with the use of immunoenzymatic methods. The concentrations of IL-17 were significantly higher in PE patients when compared to control patients. In the group of patients with PE, the levels of IL-17 positively correlated with systolic blood pressure. On the other hand, IL-17 negatively correlated with neonatal birth weight. The concentrations of PLGF were significantly lower and sENG significantly higher in studied patients when compared to controls. The PlGF/sENG ratio in the PE group was significantly lower when compared to healthy third trimester pregnant patients. In the study group, negative correlations were observed between the sENG concentrations and thrombocyte levels. The higher concentrations of IL-17 in PE could suggest its role as an inflammatory agent in the pathogenesis of the syndrome. Moreover, the negative correlation between IL-17 and a neonatal birth weight could suggest the role of the cytokine in the development of fetal growth restriction (FGR) associated with PE. It seems possible that IL-17 can be a useful marker of the risk of FGR in pregnancy complicated by PE. Furthermore, the results suggested the potential role of sENG and the PlGF/sENG ratio in the prediction of adverse outcomes such as HELLP syndrome and DIC.

Epigenetic Modifications Associated with Exposure to Endocrine Disrupting Chemicals in Patients with Gestational Diabetes Mellitus.

Gestational diabetes mellitus (GDM) remains a significant clinical and public health issue due to its increasing prevalence and the possibility for numerous short- and long-term complications. The growing incidence of GDM seems to coincide with the widespread use of endocrine disrupting chemicals (EDCs). The extensive production and common use of these substances in everyday life has resulted in constant exposure to harmful substances from the environment. That may result in epigenetic changes, which may manifest themselves also after many years and be passed on to future generations. It is important to consider the possible link between environmental exposure to endocrine disrupting chemicals (EDCs) during pregnancy, epigenetic mechanisms and an increased risk for developing gestational diabetes mellitus (GDM). This manuscript attempts to summarize data on epigenetic changes in pregnant women suffering from gestational diabetes in association with EDCs. There is a chance that epigenetic marks may serve as a tool for diagnostic, prognostic, and therapeutic measures.

The Need of Personalized Medicine in Coping with Stress during Infertility Treatment.

The term personalized medicine was created for oncological patients, but due to its positive clinical results it is now used in many other fields of medicine, including reproductive medicine. The aim of the study was to determine the level of stress and strategies of coping with stress in patients treated for infertility. The study-using a questionnaire developed by the authors, the Perceived Stress Scale-10 (PSS-10), and the Coping Orientation to Problems Experienced Inventory (Mini-COPE)-was conducted among 456 people from infertile couples. Conclusions: More than half of the studied patients demonstrated a high level of stress. The choice of coping strategies was related to the respondents' gender and level of stress as well as their experience with assisted reproductive technology.

Uterine leiomyomas: correlation between histologic composition and stiffness via magnetic resonance elastography - a Pilot Study.

OBJECTIVES: To evaluate magnetic resonance elastography as a tool for characterizing uterine leimyomas. MATERIAL AND METHODS: At total of 12 women with symptomatic leiomyomas diagnosed in physical and ultrasound examinations were enrolled in this pilot study. Before surgery, all patients underwent magnetic resonance elastography of the uterus using a 1.5 T MR whole-body scanner (Optima, GE Healthcare, Milwaukee, WI, USA). Surgical specimens were forwarded for histological examination. The findings were allocated into 3 categories depending on the percentage content of connective tissue: below 15%, from 15 to 30% and more than 30%. The median stiffness of leiomyomas for each of the group was calculated. The U-Mann Whitney test was used for statistical analysis. RESULTS: The stiffness of the leiomyomas ranged between 3.7-6.9 kPa (median value 4.9 kPa). The concentration of extracellular components in the leiomyomas did not exceed 40%. An increasing trend of the stiffness with the growing percentage of extracellular component was observed. Stiffness of the leiomyomas obtained by MRE varies depending on microscopic composition. CONCLUSIONS: The value of stiffness shows a trend of increasing with the percentage of extracellular component of the leiomyoma. Further studies are required to assess the usefulness of MRE in diagnostics of uterine leiomyomas.