Staphylococcal Resistance Patterns, blaZ and SCCmec Cassette Genes in the Nasopharyngeal Microbiota of Pregnant Women.

Antimicrobial resistance in Staphylococcus spp. colonising the nasopharynx can create risk factors of therapeutic treatment failure or prophylaxis in pregnant women. Resistance is mostly encoded on plasmids (e.g., blaZ gene for penicillinase synthesis) or chromosomes (e.g., mecA and mecC for methicillin resistance). The mecA gene is part of the chromosomal mec gene cassette (SCCmec), which is also located on the plasmid. The disc diffusion method for the selected drugs (beta-lactams, fluoroquinolones, streptogramins, aminoglicosides, macrolides, oxasolidinones, tetracyclines and other groups) was used. PCR for blaZ, mecA and mecC genes and SCCmec cassette detection and typing were performed. S. aureus (54.4%) and S. epidermidis (27.9%) were the most prevalent and showed the highest diversity of resistance profiles. The blaZ, mecA and mecC genes were reported in 95.6%, 20.6% and 1.5% of isolates, respectively. The highest resistance was found to beta-lactams, commonly used during pregnancy. Resistance to a variety of antimicrobials, including benzylpenicillin resistance in blaZ-positive isolates, and the existence of a very high diversity of SCCmec cassette structures in all staphylococci selected from the nasopharyngeal microbiota of pregnant women were observed for the first time. Knowledge of the prevalence of antimicrobial-resistant staphylococci in the nasopharynx of pregnant women may be important for the appropriate treatment or prophylaxis of this group of patients.

Epigenetic Changes in Gestational Diabetes Mellitus.

Gestational diabetes mellitus (GDM) is defined as carbohydrate intolerance that appears or is for the first time diagnosed during pregnancy. It can lead to many complications in the mother and in the offspring, so diagnostics and management of GDM are important to avoid adverse pregnancy outcomes. Epigenetic studies revealed the different methylation status of genes in pregnancies with GDM compared to pregnancies without GDM. A growing body of evidence shows that the GDM can affect not only the course of the pregnancy, but also the development of the offspring, thus contributing to long-term effects and adverse health outcomes of the progeny. Epigenetic changes occur through histone modification, DNA methylation, and disrupted function of non-coding ribonucleic acid (ncRNA) including microRNAs (miRNAs). In this review, we focus on the recent knowledge about epigenetic changes in GDM. The analysis of this topic may help us to understand pathophysiological mechanisms in GDM and find a solution to prevent their consequences.

Nesfatin-1 and Vaspin as Potential Novel Biomarkers for the Prediction and Early Diagnosis of Gestational Diabetes Mellitus.

Gestational diabetes mellitus (GDM) is considered to be one of the most frequent medical complication observed among pregnant women. The role of adipokines in the pathogenesis of GDM remains strictly unknown. Different adipokines have been studied throughout gestation, and they have been proposed as biomarkers of GDM and other pregnancy-related complications; however, there is no biomarker reported for GDM screening at present. The aim of this study was to evaluate serum nesfatin-1 and vaspin levels in GDM and non-GDM women, to characterize the correlation between these adipokines, and to assess the potential role of circulating adipokines in the prediction of risk of gestational diabetes mellitus. Serum concentrations of nesfatin-1 and vaspin were measured in 153 women with GDM, and in 84 patients with uncomplicated pregnancy by enzyme-linked immunosorbent assay (ELISA) kits, according to the manufacturer's instructions. Circulating levels of nesfatin-1 and vaspin were significantly lower in the GDM group than in the control group. Nesfatin-1 levels were negatively correlated with vaspin levels. The results of this study point out the possible role of nesfatin-1 and vaspin as potential novel biomarkers for the prediction and early diagnosis of GDM. Further studies are necessary to evaluate the influence of nesfatin-1 and vaspin on glucose metabolism in the early stages of GDM.

Adverse pregnancy outcomes and inherited thrombophilia.

AIM: (1) To evaluate the prevalence of inherited thrombophilia in pregnant women with adverse pregnancy outcomes: intrauterine growth retardation (IUGR), preeclampsia (PE) and placental abruption. (2) To assess the impact of inherited thrombophilia on the nature of obstetric complications. (3) To assess levels of protein S, protein C, antithrombin III and homocysteine in pregnant women with adverse pregnancy outcomes. SUBJECTS AND METHODS: The study comprised 162 pregnant women. The patients were divided into three test groups and one control group. In all 162 patients the following tests were completed: activated protein C resistance (APC-R), the level of free protein S, activity of protein C, antithrombin III and the level of homocysteine. The data were statistically analyzed via χ2 of independence or homogeneity test. RESULTS: In 32 of 162 patients participating in clinical research thrombophilia was diagnosed (10 patients with APC-R, 21 patients with protein S deficiency, one patient with hyperhomocysteinemia): seven patients belonged to the control group and 25 patients had diagnosed adverse pregnancy outcomes (P=0.04). In 32 patients with diagnosed thrombophilia, level of protein S was decreased (P=0.04). Protein S deficiency was diagnosed, when level of protein S was lower than 30% in the second trimester and lower than 24% in the third trimester. The incidence of activated protein C resistance caused by the mutation of factor V Leiden was in six patients (5.9%) with adverse pregnancy outcomes, and in four patients (6.6%) from the control group. Results were not statistically significant. No protein C deficiency was diagnosed (diagnosis: level<60%), but in 50% of patients with thrombophilia level of protein C was over the norm (P=0.02). The level of antithrombin III was often decreased in patients with preeclampsia - (32.4%), then in the other patients - (17.2%) (P=0.04), but no patient was diagnosed with antithrombin III deficiency (diagnosis: level<60%). CONCLUSIONS: Tests for thrombophilia should be carried out in women with adverse pregnancy outcomes in their history, who are planning pregnancy, to start anticoagulant prophylaxis. Our study supports the thesis that tests for thrombophilia should be carried out in women with a history of adverse pregnancy outcomes and who are planning a pregnancy to start anticoagulant prophylaxis.

The role of new adipokines in gestational diabetes mellitus pathogenesis.

Gestational diabetes mellitus (GDM) is defined as any degree of glucose intolerance with onset or first recognition dur-ing pregnancy. Explanation of the GDM pathogenesis is important due to preventing gestational complications. During pregnancy there are significant changes in maternal metabolism. Many of these changes are influenced by different adi-pokines produced in the placenta and adipose tissue. The exact role of adipokines in the pathogenesis of GDM remains still unknown. Several adipokines have been analysed throughout gestation and their levels have been suggested as biomarkers of maternal-perinatal outcomes. Some of them have been postulated as significant in the pathogenesis of pregnancy complications like GDM. This report aims to review some of the recent topics of adipokine research that may be of particular importance in patho-physiology and diagnosis of gestational diabetes mellitus. Because of manuscript length limitations, after thorough literature review and in view of the recent evidence, we focus on the one of the most well-known adipokine: adiponectin, and not so well-studied: nesfatin-1, chemerin, ghrelin, and CTRP 1.

Adipokines and C-peptide in overweight and obese pregnant women.

OBJECTIVES: The aim of the study was to evaluate the levels of adipokines such as adiponectin, resistin, leptin as well as C-peptide in overweight and obese pregnant women. MATERIAL AND METHODS: The adipokines and C-peptide concentrations were measured in the group of 38 overweight/obese pregnant women (BMI > 25 kg/m2) and in 42 pregnant women of normal weight (BMI < 25 kg/m2) with ELISA tests between 24th and 34th weeks of gestation. RESULTS: The overweight/obese women compared to lean ones were characterized by significantly higher concentrations of leptin (43.44 ± 31.41 vs. 21.29 ± 12.67 ng/mL, p = 0.0001) and C-peptide (2.77 ± 1.88 vs. 2.25 ± 1.42 ng/mL, p = 0.034). There were no significant differences between groups in resistin (17.39 ± 7.59 vs. 15.76 ± 6.64 ng/mL, NS) and adiponectin (6.93 ± 3.52 vs. 8.07 ± 6.53 µg/mL, NS) levels. In the overweight/obese patients, no relationships between the adipokines, C-peptide and CRP concentrations were found. BMI was negatively correlated with the resistin levels (R = -0.406, p = 0.011). The significant correlation between leptin and C-peptide concentrations was observed in the study group (R = 0.517, p = 0.012). In the control group, the negative correlation between adiponectin concentrations and BMI was shown (R = -0.446, p = 0.003). CONCLUSIONS: The higher levels of leptin in the overweight and obese pregnant women seem to reflect the leptin resistance condition and the higher levels of C-peptide in this group is suggestive for hyperinsulinemia. The positive correlation between C-peptide and leptin levels but not with resistin and adiponectin might confirm the role of leptin in the hyperinsulinemia development in overweight and obesity during pregnancy.

Prevalence of Culturable Bacteria and Yeasts in the Nasopharynx Microbiota during the Physiological Course of Pregnancy.

The aim of the study was to compare the prevalence of the nasopharyngeal carriage of culturable microorganisms in the microbiota of asymptomatic women with a physiological pregnancy (PW) and nonpregnant women (NPW). Nasopharyngeal swabs were collected from 53 PW and 30 NPW to detect bacterial and fungal colonization. Isolates were identified using the culture method and the MALDI-TOF MS technique. The nasopharyngeal microbiota (NPM) partially differed between PW and NPW. These differences in the frequency of nasopharyngeal colonization between the PW and NPW groups were not statistically significant (p > 0.05); all cases were colonized by bacteria and only two cases in the PW group were colonized by yeasts, namely, Rhodotorula spp. High levels of staphylococcal colonization, including predominantly coagulase-negative staphylococci and S. aureus in the nasopharyngeal sample, were present in both groups. The reduced number of Gram-negative rods colonized in the cases studied was seen in samples from the NPW group, particularly with Enterobacterales, and anaerobic Cutibacterium spp. were isolated only in the PW group (p < 0.05). Moreover, a higher carriage rate of Enterobacter aerogenes colonization was statistically significant (p < 0.05) and correlated with the NPW group. Pregnancy may disturb the composition of the NPM represented by commensals and opportunistic bacteria and promote yeast colonization as compared to nonpregnant women.

The State of Health and the Quality of Life in Women Suffering from Endometriosis.

Quality of life is related to good health, family relations, feeling of self-esteem, and ability to cope with difficult situations. Endometriosis is a chronic condition which affects different areas of life. The lack of satisfaction in everyday life is mainly due to constant pain. The process of adjusting to a life with illness is associated with negative emotions. The aim of the article is to review the current state of knowledge concerning the impact of social and medical factors on a population of women affected by endometriosis. Women with endometriosis have an impaired quality of life compared to the general female population. Psychological consequences of endometriosis include: depression, anxiety, powerlessness, guilt, self-directed violence, and deterioration of interpersonal relations. It may contribute to lower productivity at work and less satisfying intimate life. A multi-disciplinary, evidence-based care is needed. The disease can take away the ability to be physically active, obtain an education, work continuously, and interact with friends. Social support and cognitive-behavioral therapy are extremely important for healing.

Metformin as a Potential Treatment Option for Endometriosis.

Endometriosis is a common disease in women of reproductive age, and its pathogenesis seems to be largely affected by hormone imbalance, inflammation, oxidative stress, and autophagy dysregulation. These pathophysiological disturbances interact with one another through mechanisms that are still awaiting elucidation. The aim of this article is to present current knowledge regarding the possibilities of using metformin in the pharmacological treatment of endometriosis. Metformin is an insulin sensitizer widely used for the treatment of type 2 diabetes mellitus. The pleiotropic effects of metformin are mainly exerted through the activation of AMP-activated protein kinase, which is the key cellular energy homeostasis regulator that inhibits mTOR, a major autophagy suppressor. Metformin regresses endometriotic implants by increasing the activity of superoxide dismutase. It is also an inhibitor of metalloproteinase-2, decreasing the levels of the vascular endothelial growth factor and matrix metalloproteinase-9 in animal studies. In endometriosis, metformin might modify the stroma-epithelium communication via Wnt2/ß-catenin. With its unique therapeutic mechanisms and no serious side effects, metformin seems to be a helpful anti-inflammatory and anti-proliferative agent in the treatment of endometriosis. It could be a missing link for the successful treatment of this chronic disease.

Evolution of Gestational Diabetes Mellitus across Continents in 21st Century.

Over the last few decades, several definitions of gestational diabetes mellitus (GDM) have been described. There is currently not enough research to show which way is the best to diagnose GDM. Opinions differ in terms of the optimal screening and diagnostic measures, in part due to the differences in the population risks, the cost-effectiveness considerations, and the lack of an evidence base to support large national screening programs. The basic method for identifying the disease is the measurement of glucose plasma levels which may be determined when fasting, two hours after a meal, or simply at any random time. The currently increasing incidence of diabetes in the whole population, the altering demographics and the presence of lifestyle changes still require better methods of screening for hyperglycemia, especially during pregnancy. The main aim of this review is to focus on the prevalence and modifications to the screening criteria for GDM across all continents in the 21st century. We would like to show the differences in the above issues and correlate them with the geographical situation. Looking at the history of diabetes, we are sure that more than one evolution in GDM diagnosis will occur, due to the development of medicine, appearance of modern technologies, and the dynamic continuation of research.

Prevention of Hypertensive Disorders of Pregnancy-Is There a Place for Metformin?

The possibility of prophylaxis of hypertensive disorders of pregnancy (HDPs) such as preeclampsia (PE) and pregnancy-induced hypertension is of interest due to the unpredictable course of these diseases and the risks they carry for both mother and fetus. It has been proven that their development is associated with the presence of the placenta, and the processes that initiate it begin at the time of the abnormal invasion of the trophoblast in early pregnancy. The ideal HDP prophylaxis should alleviate the influence of risk factors and, at the same time, promote physiological trophoblast invasion and maintain the physiologic endothelium function without any harm to both mother and fetus. So far, aspirin is the only effective and recommended pharmacological agent for the prevention of HDPs in high-risk groups. Metformin is a hypoglycemic drug with a proven protective effect on the cardiovascular system. Respecting the anti-inflammatory properties of metformin and its favorable impact on the endothelium, it seems to be an interesting option for HDP prophylaxis. The results of previous studies on such use of metformin are ambiguous, although they indicate that in a certain group of pregnant women, it might be effective in preventing hypertensive complications. The aim of this study is to present the possibility of metformin in the prevention of hypertensive disorders of pregnancy with respect to its impact on the pathogenic elements of development.

The Potential Role of Chemerin, Lipocalin 2, and Apelin in the Diagnosis and Pathophysiology of Gestational Diabetes Mellitus.

The exact role of adipokines in the pathogenesis of gestational diabetes mellitus (GDM) still remains not fully clear, and multiple studies have analyzed their potential contribution to the pathophysiology of this pregnancy complication. This study is aimed at evaluating serum chemerin, lipocalin 2, and apelin concentrations in GDM and healthy pregnant patients, assessing the correlation between these adipokines, and suggesting the potential role of these cytokines in the diagnosis and pathophysiology of GDM. The study comprised 237 pregnant women: 153 with GDM and 84 with physiological pregnancy. Serum concentrations of chemerin, lipocalin 2, and apelin were obtained at 24-29 weeks of gestation. The mean concentrations of chemerin and lipocalin 2 were significantly higher in the GDM group. The concentration of apelin was slightly higher in the GDM group, but not statistically significant. The strong positive correlation between chemerin and lipocalin 2 concentrations was noticed in both groups. Our data suggest that maternal chemerin and lipocalin 2 may play a significant role in the pathophysiology of GDM. We imply that these adipokines could potentially be established as novel biomarkers for the early identification of GDM. However, more studies are needed to analyze the effect of these adipokines on glucose metabolism during early pregnancy.

Ovarian Cancer and Pregnancy-A Current Problem in Perinatal Medicine: A Comprehensive Review.

The frequency of concomitant adnexal tumors in pregnancy is reported to be at 0.15-5.7%, while ovarian cancer complicates 1 in 15,000 to 1 in 32,000 pregnancies, being the second most common gynecologic cancer diagnosed during pregnancy. The aim of this review is to discuss the problem of ovarian cancer complicating pregnancy and the current recommendations for diagnostics and treatment, with an emphasis on the risk to the fetus. A detailed analysis of the literature found in the PubMed and MEDLINE databases using the keywords "ovarian cancer", "ovarian malignancy", "adnexal masses", "ovarian tumor" and "pregnancy" was performed. There were no studies on a large series of pregnant women treated for ovarian malignancies and the management has not been well established. The diagnostics and therapeutic procedures need to be individualized with respect to the histopathology of the tumor, its progression, the gestational age at the time of diagnosis and the mother's decisions regarding pregnancy preservation. The multidisciplinary cooperation of specialists in perinatal medicine, gynecological oncology, chemotherapy, neonatology and psychology seems crucial in order to obtain the best possible maternal and neonatal outcomes.

Adipokines and Endothelium Dysfunction Markers in Pregnant Women with Gestational Hypertension.

OBJECTIVE: The aim of the study was to evaluate the levels of adipokines such as adiponectin and leptin as well as soluble intercellular adhesion molecule-1 (sICAM-1) and endogenous NOS inhibitor-asymmetric dimethylarginine (ADMA), as the endothelium dysfunction markers in pregnant women with gestational hypertension (GH). PATIENTS AND METHODS: Adiponectin, leptin, sICAM-1, and ADMA concentrations were measured in a group of 34 patients with GH and in 32 healthy pregnant women between the 24th and 34th week of gestation with ELISA tests. RESULTS: The patients with GH compared with healthy ones were characterized by significantly higher BMI (28.09 ± 7.90 vs. 22.34 ± 4.21 kg/m2, p=0.016) and higher concentrations of leptin (45.89 ± 35.91 vs. 24.09 ± 24.40 ng/mL, p=0.006). sICAM-1 levels were also higher in the GH group but without the statistical significance (264.51 ± 50.99 vs. 232.56 ± 43.3 ng/ml, p=0.057). There were no significant differences between groups in adiponectin (8.79 ± 8.67 vs. 7.90 ± 3.71 µg/mL, p=0.46, NS) and ADMA (0.57 ± 0.26 vs. 0.60 ± 0.24 µmol/L, p=0.68, NS) levels. The significant correlation between leptin levels and BMI value was observed only in patients with GH (R = 0.56, p=0.02). CONCLUSIONS: The higher levels of leptin in pregnant women with gestational hypertension may be suggestive of the role of leptin in GH development. As the patients in the GH group had higher BMI, hyperleptinemia may link obesity with gestational hypertension. The significance of leptin as the predictive marker of GH development could be implied. It could be postulated that the higher levels of sICAM-1 in the GH patients, although not statistically significant, could reflect some impairment of the endothelium function occurring in GH regardless of BMI. The comparable adiponectin levels in GH and healthy pregnant patients and the lack of its correlation with BMI may indicate the occurrence of a protective mechanism in pregnancy maintaining its concentration and preserving from the consequences of the decrease in its levels in overweight and obese patients. Since ADMA levels were similar in GH and healthy pregnant women, ADMA seems not to be involved in GH pathogenesis, suggesting that NO synthesis is not impaired in this pregnancy complication. As the data on the gestational hypertension pathogenesis and its correlations with adipokines and markers of the endothelium dysfunction are limited, further studies on this issue are warranted.

Adiponectin and Omentin Levels as Predictive Biomarkers of Preterm Birth in Patients with Gestational Diabetes Mellitus.

OBJECTIVE: The aim of this study was to determine any changes in adiponectin and omentin levels in GDM patients who delivered at term and preterm and to evaluate whether adipokines can be useful as a clinical biomarker to predict subsequent preterm delivery. PATIENTS AND METHODS: The levels of adiponectin and omentin were measured in four groups: (1) women with GDM who delivered at term (n=63); (2) women with GDM who had the symptoms of threatened preterm labor and delivered at term (n=23); (3) women with GDM and spontaneous preterm birth (before 37 completed weeks of gestation) (n=19); (4) women with physiological pregnancy (n=55). RESULTS: In comparison with control group the median adiponectin concentrations were significantly lower in all GDM groups (10737 versus 8879; 7057; 6253 ng/ml, respectively; p<0.01). The median omentin concentrations were also significantly lower in all GDM groups in comparison with control group (469 versus 432; 357; 308 ng/ml, respectively; p<0.01). No significant differences in adiponectin and omentin levels between the GDM, preterm labor, and preterm birth groups were observed. However, there was a trend towards lower adiponectin and omentin levels in preterm birth group. The strong correlations between adiponectin and omentin levels were observed in all groups (R=0.801, p<0.001; R=0.824, p<0.001; R=0.705, p<0.001; R=0.764, respectively; p<0.001). In the univariable logistic regression model, significant correlation between omentin concentrations and preterm birth occurrence was found. CONCLUSIONS: Our findings suggest that omentin-1, rather than adiponectin, could be useful as a predictor of preterm birth in patients with gestational diabetes mellitus.

An Unusual Coexistence of Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma with Endometrioid-Type Endometrial Cancer in a 58-Year-Old Woman: A Case Study with Literature Review.

INTRODUCTION: The coexistence of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) with different gynecologic neoplasms is a rare phenomenon. Here, we report a case of simultaneously developed CLL/SLL with endometrioid-type uterine cancer. CASE REPORT: A 58-year-old woman was admitted to the 2nd Department of Gynecology, Lublin Medical University, Lublin, Poland, in June 2017, where the uterine cancer was diagnosed. After the surgery, pathological examination revealed a uterine moderately differentiated adenocarcinoma of endometrioid subtype (subtype I according to Bokhman) deeply infiltrating the myometrium as well as the uterine cervix. Surprisingly, CLL/SLL was subsequently diagnosed in all removed pelvic as well as para-aortic lymph nodes. Immunohistochemical analysis showed CD45 (++), CD20 (+), CD3 (-/+), CD19 (+), CD23 (+), CD5 (+), and CD34 (+). Proliferative activity, assessed by MIB-1 proliferative index immunostaining, reached 18%. The patient was admitted to radiotherapy and chemotherapy at the Oncology Hospital, Lublin, Poland, and is still on follow-up. CONCLUSIONS: The coexistence of CLL/SLL with various gynecological malignancies, especially primary human endometrial cancer, is a rare entity. The detection of both tumors simultaneously, in general, is accidental, and the management should not be different from the situation in which malignancy appears de novo.

Intra-uterine Growth Retardation as a Risk Factor of Postnatal Metabolic Disorders.

Intra-uterine growth retardation (IUGR) represents one of the major problems in perinatal medicine. IUGR is one of main causes of perinatal mortality and morbidity. A huge number and variety of established and possible causes of IUGR have been described. There are currently no data about effective treatment of this fetal condition. IUGR has been described to be strictly involved in fetal programming. Fetal programming is the general idea, which tells us how during development of the embryo and fetus significant physiological parameters can be shaped by environmental events. A link between the intra-uterine growth retardation and the risk of developing type 2 diabetes, obesity and cardiovascular disease postnatally has been well documented. The aim of this paper is to present an overview of the current knowledge of IUGR effects on development of hypertension and cardiovascular diseases, impact on insulin secretion and resistance, diabetes mellitus and metabolic syndrome. The influence of intrauterine growth retardation on predisposition to obesity and adipose dysfunction was also described.

Urban vs. rural patients. Differences in stage and overall survival among patients treated surgically for lung cancer.

INTRODUCTION: Besides the undoubted influence of risk factors on morbidity and survival time, there are also other environmental factors, such as awareness of the prevalence of risk factors and the availability of modern diagnosis and treatment methods. OBJECTIVE: To evaluate differences in lung cancer 5-year overall survival rates between urban and rural patients hospitalized in the Department of Thoracic Surgery of the Medical University in Lublin, Poland, and possible influence of several risk factors on these rates. MATERIALS AND METHODS: The analysis was based on 125 lung cancer patients who underwent surgical procedures in years 2006-2007 and who agreed to take part in the survey. The study aimed at recognition of the health situation and selected demographic traits of people who had been treated surgically for lung cancer. The differences were evaluated between rural and urban inhabitants in gender, age, lung function, smoking habits, exposure to risk factors at work, family history of cancer, staging of the disease, histological type of cancer, post-surgical treatment, and their possible influence on overall survival. RESULTS: The results showed that the only noted differences between urban and rural population were in tobacco smoking and lung function. Survival rates were very similar and did not differ from the European average. CONCLUSIONS: The assumption that Polish rural patients are presenting with later cancer stages at the time of diagnosis, and have worse chances for survival, has become invalid in modern times.