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Breast cancer incidence is actually the highest one among all cancers. Overall breast cancer management is associated with challenges considering risk assessment and predictive diagnostics, targeted prevention of metastatic disease, appropriate treatment options, and cost-effectiveness of approaches applied. Accumulated research evidence indicates promising anti-cancer effects of phytochemicals protecting cells against malignant transformation, inhibiting carcinogenesis and metastatic spread, supporting immune system and increasing effectiveness of conventional anti-cancer therapies, among others. Molecular and sub-/cellular mechanisms are highly complex affecting several pathways considered potent targets for advanced diagnostics and cost-effective treatments. Demonstrated anti-cancer affects, therefore, are clinically relevant for improving individual outcomes and might be applicable to the primary (protection against initial cancer development), secondary (protection against potential metastatic disease development), and tertiary (towards cascading complications) care. However, a detailed data analysis is essential to adapt treatment algorithms to individuals' and patients' needs. Consequently, advanced concepts of patient stratification, predictive diagnostics, targeted prevention, and treatments tailored to the individualized patient profile are instrumental for the cost-effective application of natural anti-cancer substances to improve overall breast cancer management benefiting affected individuals and the society at large., Competing Interests: Conflict of interestThe authors declare no competing interest., (© The Author(s) 2022.)

Homocysteine (Hcy) metabolism is crucial for regulating methionine availability, protein homeostasis, and DNA-methylation presenting, therefore, key pathways in post-genomic and epigenetic regulation mechanisms. Consequently, impaired Hcy metabolism leading to elevated concentrations of Hcy in the blood plasma (hyperhomocysteinemia) is linked to the overproduction of free radicals, induced oxidative stress, mitochondrial impairments, systemic inflammation and increased risks of eye disorders, coronary artery diseases, atherosclerosis, myocardial infarction, ischemic stroke, thrombotic events, cancer development and progression, osteoporosis, neurodegenerative disorders, pregnancy complications, delayed healing processes, and poor COVID-19 outcomes, among others. This review focuses on the homocysteine metabolism impairments relevant for various pathological conditions. Innovative strategies in the framework of 3P medicine consider Hcy metabolic pathways as the specific target for in vitro diagnostics, predictive medical approaches, cost-effective preventive measures, and optimized treatments tailored to the individualized patient profiles in primary, secondary, and tertiary care., Competing Interests: Competing interestsThe authors declare no competing interests., (© The Author(s) 2021.)

Inflammation is an essential pillar of the immune defense. On the other hand, chronic inflammation is considered a hallmark of cancer initiation and progression. Chronic inflammation demonstrates a potential to induce complex changes at molecular, cellular, and organ levels including but not restricted to the stagnation and impairment of healing processes, uncontrolled production of aggressive ROS/RNS, triggered DNA mutations and damage, compromised efficacy of the DNA repair machinery, significantly upregulated cytokine/chemokine release and associated patho-physiologic protein synthesis, activated signaling pathways involved in carcinogenesis and tumor progression, abnormal tissue remodeling, and created pre-metastatic niches, among others. The anti-inflammatory activities of flavonoids demonstrate clinically relevant potential as preventive and therapeutic agents to improve individual outcomes in diseases linked to the low-grade systemic and chronic inflammation, including cancers. To this end, flavonoids are potent modulators of pro-inflammatory gene expression being, therefore, of great interest as agents selectively suppressing molecular targets within pro-inflammatory pathways. This paper provides in-depth analysis of anti-inflammatory properties of flavonoids, highlights corresponding mechanisms and targeted molecular pathways, and proposes potential treatment models for multi-level cancer prevention in the framework of predictive, preventive, and personalized medicine (PPPM / 3PM). To this end, individualized profiling and patient stratification are essential for implementing targeted anti-inflammatory approaches. Most prominent examples are presented for the proposed application of flavonoid-conducted anti-inflammatory treatments in overall cancer management., Supplementary Information: The online version contains supplementary material available at 10.1007/s13167-021-00257-y., Competing Interests: Conflict of interestThe authors declare no competing interests., (© The Author(s) 2021.)

Aims: Coronavirus disease 2019 is responsible for a worldwide increase in morbidity and mortality. The relationship of this infection to mother-to-child vertical transmission has not been elucidated yet. However, recent reports indicate a foetal death rate of up to 3%., Methods: We report a case of sudden pre-term foetal demise in a woman positive for SARS-CoV-2 but asymptomatic, with physiological course of pregnancy., Results: One of the possible explanations of sudden foetal death may be acute placental insufficiency caused by a SARS-CoV-2 placental infection or the development of foetal inflammatory response syndrome (FIRS)., Conclusion: Considering the potential risk of foetal demise, questions remain regarding foetal monitoring and the timing of labour and delivery in the second and third trimesters, particularly in asymptomatic or mild maternal SARS-CoV-2 infection. A relevant multidisciplinary team must also be aware of these risks associated with possibly fatal consequences.

Objectives: Multiple sclerosis (MS) is a chronic autoimmune and neurodegenerative disease. This study evaluated pregnancy-related issues in patients with MS in one perinatological centre., Material and Methods: A single-centre, retrospective study of the perinatal period in patients with MS admitted at the Dpt. of Gynaecology and Obstetrics, Jessenius Faculty of Medicine, Comenius University and the University Hospital in Martin, Slovak Republic, European Union from January 1, 2015 to December 1, 2020 was performed. Selected parameters from personal, obstetric, and neurological histories were analysed., Results: A cohort of 15 patients (32.5±5.3 years) with a relapsing-remitting form of MS gave birth to 16 children. The mean length of MS at the time of delivery was 9±3.6 years. The severity of the Expanded Disability Status Scale score was 2.0±1.5. Caesarean section (CS) was indicated in 14 deliveries (87.5%). It was elective CS in 10 patients. The most common indication for elective CS was a combination of significant chronic fatigue syndrome and neurological deficit (paresis)., Conclusions: The basis for the management of pregnancy, childbirth, and the postpartum period in women with MS is a planned pregnancy based on close cooperation among patients, gynaecologists, and neurologists. Vaginal delivery is not primarily contraindicated. Indications for CS should be considered individually. One way to minimise the indications for CS is a more accurate diagnosis and personalised treatment of fatigue in pregnant women with MS. Presumably, both obstetricians and neurologists prefer vaginal delivery as the first choice in patients with fatigue syndrome.

An increasing interest in a healthy lifestyle raises questions about optimal body weight. Evidently, it should be clearly discriminated between the standardised "normal" body weight and individually optimal weight. To this end, the basic principle of personalised medicine "one size does not fit all" has to be applied. Contextually, "normal" but e.g. borderline body mass index might be optimal for one person but apparently suboptimal for another one strongly depending on the individual genetic predisposition, geographic origin, cultural and nutritional habits and relevant lifestyle parameters-all included into comprehensive individual patient profile. Even if only slightly deviant, both overweight and underweight are acknowledged risk factors for a shifted metabolism which, if being not optimised, may strongly contribute to the development and progression of severe pathologies. Development of innovative screening programmes is essential to promote population health by application of health risks assessment, individualised patient profiling and multi-parametric analysis, further used for cost-effective targeted prevention and treatments tailored to the person. The following healthcare areas are considered to be potentially strongly benefiting from the above proposed measures: suboptimal health conditions, sports medicine, stress overload and associated complications, planned pregnancies, periodontal health and dentistry, sleep medicine, eye health and disorders, inflammatory disorders, healing and pain management, metabolic disorders, cardiovascular disease, cancers, psychiatric and neurologic disorders, stroke of known and unknown aetiology, improved individual and population outcomes under pandemic conditions such as COVID-19. In a long-term way, a significantly improved healthcare economy is one of benefits of the proposed paradigm shift from reactive to Predictive, Preventive and Personalised Medicine (PPPM/3PM). A tight collaboration between all stakeholders including scientific community, healthcare givers, patient organisations, policy-makers and educators is essential for the smooth implementation of 3PM concepts in daily practice., Competing Interests: Conflict of interestThe authors declare no competing interests., (© The Author(s) 2021.)

Multi-factorial mitochondrial damage exhibits a "vicious circle" that leads to a progression of mitochondrial dysfunction and multi-organ adverse effects. Mitochondrial impairments (mitochondriopathies) are associated with severe pathologies including but not restricted to cancers, cardiovascular diseases, and neurodegeneration. However, the type and level of cascading pathologies are highly individual. Consequently, patient stratification, risk assessment, and mitigating measures are instrumental for cost-effective individualized protection. Therefore, the paradigm shift from reactive to predictive, preventive, and personalized medicine (3PM) is unavoidable in advanced healthcare. Flavonoids demonstrate evident antioxidant and scavenging activity are of great therapeutic utility against mitochondrial damage and cascading pathologies. In the context of 3PM, this review focuses on preclinical and clinical research data evaluating the efficacy of flavonoids as a potent protector against mitochondriopathies and associated pathologies.

The risks related to the COVID-19 are multi-faceted including but by far not restricted to the following: direct health risks by poorly understood effects of COVID-19 infection, overloaded capacities of healthcare units, restricted and slowed down care of patients with non-communicable disorders such as cancer, neurologic and cardiovascular pathologies, among others; social risks-restricted and broken social contacts, isolation, professional disruption, explosion of aggression in the society, violence in the familial environment; mental risks-loneliness, helplessness, defenceless, depressions; and economic risks-slowed down industrial productivity, broken delivery chains, unemployment, bankrupted SMEs, inflation, decreased capacity of the state to perform socially important programs and to support socio-economically weak subgroups in the population. Directly or indirectly, the above listed risks will get reflected in a healthcare occupation and workload which is a tremendous long-term challenge for the healthcare capacity and robustness. The article does not pretend to provide solutions for all kind of health risks. However, it aims to present the scientific evidence of great clinical utility for primary, secondary, and tertiary care to protect affected individuals in a cost-effective manner. To this end, due to pronounced antimicrobial, antioxidant, anti-inflammatory, and antiviral properties, naturally occurring plant substances are capable to protect affected individuals against COVID-19-associated life-threatening complications such as lung damage. Furthermore, they can be highly effective, if being applied to secondary and tertiary care of noncommunicable diseases under pandemic condition. Thus, the stratification of patients evaluating specific health conditions such as sleep quality, periodontitis, smoking, chronic inflammation and diseases, metabolic disorders and obesity, vascular dysfunction, and cancers would enable effective managemenet of COVID-19-associated complications in primary, secondary, and tertiary care in the context of predictive, preventive, and personalized medicine (3PM)., Competing Interests: Conflict of interestThe authors declare no competing interests., (© The Author(s) 2021.)

Cervical cancer (CC) is one of the most common cancers of the female reproductive system. In advanced stages, it might lead to metastases via hematogenous or lymphatic spread. Patients with hematogenous metastases are less common with a higher risk of death. This article focuses on a case of CC with comedo-like spinocellular skin metastases. These structures, typical for basaloid squamous cell carcinoma, represent an uncommon and extremely rare finding even in advanced CC and are associated with a poor prognosis.

Metabolic reprogramming characterized by alterations in nutrient uptake and critical molecular pathways associated with cancer cell metabolism represents a fundamental process of malignant transformation. Melatonin (N-acetyl-5-methoxytryptamine) is a hormone secreted by the pineal gland. Melatonin primarily regulates circadian rhythms but also exerts anti-inflammatory, anti-depressant, antioxidant and anti-tumor activities. Concerning cancer metabolism, melatonin displays significant anticancer effects via the regulation of key components of aerobic glycolysis, gluconeogenesis, the pentose phosphate pathway (PPP) and lipid metabolism. Melatonin treatment affects glucose transporter (GLUT) expression, glucose-6-phosphate dehydrogenase (G6PDH) activity, lactate production and other metabolic contributors. Moreover, melatonin modulates critical players in cancer development, such as HIF-1 and p53. Taken together, melatonin has notable anti-cancer effects at malignancy initiation, progression and metastasing. Further investigations of melatonin impacts relevant for cancer metabolism are expected to create innovative approaches supportive for the effective prevention and targeted therapy of cancers.

HPVs representing the most common sexually transmitted disease are a group of carcinogenic viruses with different oncogenic potential. The immune system and the vaginal microbiome represent the modifiable and important risk factors in HPV-induced carcinogenesis. HPV infection significantly increases vaginal microbiome diversity, leading to gradual increases in the abundance of anaerobic bacteria and consequently the severity of cervical dysplasia. Delineation of the exact composition of the vaginal microbiome and immune environment before HPV acquisition, during persistent/progressive infections and after clearance, provides insights into the complex mechanisms of cervical carcinogenesis. It gives hints regarding the prediction of malignant potential. Relative high HPV prevalence in the general population is a challenge for modern and personalized diagnostics and therapeutic guidelines. Identifying the dominant microbial biomarkers of high-grade and low-grade dysplasia could help us to triage the patients with marked chances of lesion regression or progression. Any unnecessary surgical treatment of cervical dysplasia could negatively affect obstetrical outcomes and sexual life. Therefore, understanding the effect and role of microbiome-based therapies is a breaking point in the conservative management of HPV-associated precanceroses. The detailed evaluation of HPV capabilities to evade immune mechanisms from various biofluids (vaginal swabs, cervicovaginal lavage/secretions, or blood) could promote the identification of new immunological targets for novel individualized diagnostics and therapy. Qualitative and quantitative assessment of local immune and microbial environment and associated risk factors constitutes the critical background for preventive, predictive, and personalized medicine that is essential for improving state-of-the-art medical care in patients with cervical precanceroses and cervical cancer. The review article focuses on the influence and potential diagnostic and therapeutic applications of the local innate immune system and the microbial markers in HPV-related cancers in the context of 3P medicine., Competing Interests: Conflicts of interestThe authors declare no competing interests., (© European Association for Predictive, Preventive and Personalised Medicine (EPMA) 2021.)

Cost-efficacy of currently applied treatments is an issue in overall cancer management challenging healthcare and causing tremendous economic burden to societies around the world. Consequently, complex treatment models presenting concepts of predictive diagnostics followed by targeted prevention and treatments tailored to the personal patient profiles earn global appreciation as benefiting the patient, healthcare economy, and the society at large. In this context, application of flavonoids as a spectrum of compounds and their nano-technologically created derivatives is extensively under consideration, due to their multi-faceted anti-cancer effects applicable to the overall cost-effective cancer management, primary, secondary, and even tertiary prevention. This article analyzes most recently updated data focused on the potent capacity of flavonoids to promote anti-cancer therapeutic effects and interprets all the collected research achievements in the frame-work of predictive, preventive, and personalized (3P) medicine. Main pillars considered are: - Predictable anti-neoplastic, immune-modulating, drug-sensitizing effects; - Targeted molecular pathways to improve therapeutic outcomes by increasing sensitivity of cancer cells and reversing their resistance towards currently applied therapeutic modalities., Competing Interests: Conflict of interestThe authors declare no conflict of interest., (© The Author(s) 2021.)

MicroRNAs (miRNAs) are one of the important regulators of cellular functions fundamental for healthy pregnancy processes, including angiogenesis and differentiation of trophoblast cells, and their deregulation could be implicated in the pathogenesis of pregnancy complications, including preeclampsia (PE). The aim of this study was to assess the association of miRNA expression in plasma samples with PE, its onset, and severity. Our study enrolled 59 pregnant women, 27 in the preeclamptic study group and 32 in the control group with physiological pregnancy. Preeclamptic pregnancies were divided into subgroups based on the severity and onset of disease. Relative expression of miR-21-5p, miR-155-5p, miR-210-5p, miR-16-5p, and miR-650 isolated from plasma samples was analysed by quantitative real-time PCR and normalised to experimentally established reference genes. Our results revealed upregulation of miR-21-5p (1.16-fold change, p = 0.0015), miR-155-5p (1.62-fold change, p = 0.0005) in preeclamptic pregnancies, compared to controls. Overexpression of these two miRNAs was observed, especially in subgroups of severe and late-onset PE compared to healthy pregnancies. Although we hypothesised that the expression level of studied miRNAs could vary between PE subtypes (mild vs. severe, early onset vs. late-onset), no obvious differences were detected. In conclusion, our study could contribute to the large-scale studies for the identification of non-invasive biomarkers for PE detection to improve outcomes for women and their new-borns.

Metastasis represents a major obstacle in cancer treatment and the leading cause of cancer-related deaths. Therefore, the identification of compounds targeting the multi-step and complex process of metastasis could improve outcomes in the management of cancer patients. Carotenoids are naturally occurring pigments with a plethora of biological activities. Carotenoids exert a potent anti-cancer capacity in various cancer models in vitro and in vivo, mediated by the modulation of signaling pathways involved in the migration and invasion of cancer cells and metastatic progression, including key regulators of the epithelial-mesenchymal transition and regulatory molecules, such as matrix metalloproteinases (MMPs), tissue inhibitors of metalloproteinases (TIMPs), urokinase plasminogen activator (uPA) and its receptor (uPAR), hypoxia-inducible factor-1α (HIF-1α), and others. Moreover, carotenoids modulate the expression of genes associated with cancer progression and inflammatory processes as key mediators of the complex process involved in metastasis. Nevertheless, due to the predominantly preclinical nature of the known anti-tumor effects of carotenoids, and unclear results from certain carotenoids in specific cancer types and/or specific parts of the population, a precise analysis of the anti-cancer effects of carotenoids is essential. The identification of carotenoids as effective compounds targeting the complex process of cancer progression could improve the outcomes of advanced cancer patients.

Objective: In our review article we focused on the circulating HPV DNA and its potential role in the pathogenesis of cervical cancer and in the evaluation of patients´ prognosis with cervical cancer Design: The article is a systematic review study analyzing available scientific articles focused on the circulating HPV DNA., Setting: Clinic of Obstetrics and Gynecology, Jesenius faculty of Medicine in Martin, Comenius University in Bratislava, Slovakia., Methods: In our study we searched the medical database PubMed with the key words: circulating HPV DNA, cervical cancer, cervical precanceroses. The core of our work is focused on the scientific articles published in English language since year 1995., Results: We identified 13 studies in PubMed database analyzing the circulating HPV DNA in the process of cervical carcinogenesis. It is clear from the results that circulating HPV DNA is a significant prognostic marker of cervical malignant diseases including the early stages., Conclusion: The results focused on circulating HPV DNA show the significance of molecular biology in assessing the prognosis of cervical cancer. This idea has to be supported by further relevant studies. The uniformity of studies and use of the most sophisticated methods could help to answer the question about the real role of circulating HPV DNA in the process of cervical carcinogenesis and disease progression.

Purpose: The formation of new blood vessels from previous ones, angiogenesis, is critical in tissue repair, expansion or remodeling in physiological processes and in various pathologies including cancer. Despite that, the development of anti-angiogenic drugs has great potential as the treatment of cancer faces many problems such as development of the resistance to treatment or an improperly selected therapy approach. An evaluation of predictive markers in personalized medicine could significantly improve treatment outcomes in many patients., Methods: This comprehensive review emphasizes the anticancer potential of flavonoids mediated by their anti-angiogenic efficacy evaluated in current preclinical and clinical cancer research., Results and Conclusion: Flavonoids are important groups of phytochemicals present in common diet. Flavonoids show significant anticancer effects. The anti-angiogenic effects of flavonoids are currently a widely discussed topic of preclinical cancer research. Flavonoids are able to regulate the process of tumor angiogenesis through modulation of signaling molecules such as VEGF, MMPs, ILs, HIF or others. However, the evaluation of the anti-angiogenic potential of flavonoids within the clinical studies is not frequently discussed and is still of significant scientific interest.

Breast cancer, which is the most common malignancy in women, does not form a uniform nosological unit but represents a group of malignant diseases with specific clinical, histopathological, and molecular characteristics. The increasing knowledge of the complex pathophysiological web of processes connected with breast cancercarcinogenesis allows the development of predictive and prognostic gene expressionand molecular classification systems with improved risk assessment, which could be used for individualized treatment. In our review article, we present the up-to-date knowledge about the role of miRNAs and their prognostic and predictive value in luminal A breast cancer. Indeed, an altered expression profile of miRNAs can distinguish not only between cancer and healthy samples, but they can classify specific molecular subtypes of breast cancer including HER2, Luminal A, Luminal B, and TNBC. Early identification and classification of breast cancer subtypes using miRNA expression profilescharacterize a promising approach in the field of personalized medicine. A detection of sensitive and specific biomarkers to distinguish between healthy and early breast cancer patients can be achieved by an evaluation of the different expression of several miRNAs. Consequently, miRNAs represent a potential as good diagnostic, prognostic, predictive, and therapeutic biomarkers for patients with luminal A in the early stage of BC.

Metastasis represents a serious complication in the treatment of cancer. Flavonoids are plant secondary metabolites exerting various health beneficiary effects. The effects of flavonoids against cancer are associated not only with early stages of the cancer process, but also with cancer progression and spread into distant sites. Flavonoids showed potent anti-cancer effects against various cancer models in vitro and in vivo, mediated via regulation of key signaling pathways involved in the migration and invasion of cancer cells and metastatic progression, including key regulators of epithelial-mesenchymal transition or regulatory molecules such as MMPs, uPA/uPAR, TGF-β and other contributors of the complex process of metastatic spread. Moreover, flavonoids modulated also the expression of genes associated with the progression of cancer and improved inflammatory status, a part of the complex process involved in the development of metastasis. Flavonoids also documented clear potential to improve the anti-cancer effectiveness of conventional chemotherapeutic agents. Most importantly, flavonoids represent environmentally-friendly and cost-effective substances; moreover, a wide spectrum of different flavonoids demonstrated safety and minimal side effects during long-termed administration. In addition, the bioavailability of flavonoids can be improved by their conjugation with metal ions or structural modifications by radiation. In conclusion, anti-cancer effects of flavonoids, targeting all phases of carcinogenesis including metastatic progression, should be implemented into clinical cancer research in order to strengthen their potential use in the future targeted prevention and therapy of cancer in high-risk individuals or patients with aggressive cancer disease with metastatic potential.

Preeclampsia is a multisystemic disorder that occurs in 5-8% of pregnant women and remains a leading cause of both maternal and fetal morbidity and mortality. The disease is characterized by the abnormal vascular response to placentation, but the exact pathophysiology and pathogenesis of preeclampsia remain unknown. Risk factors for preeclampsia include increased maternal age, obesity, multiple gestations, and a history of preeclampsia. Several studies have suggested that altered expression of some microRNAs (miRNAs) in placental tissue, and maternal circulation, may be associated with several types of pregnancy complications such as preeclampsia, preterm birth, and spontaneous abortion. It is assumed that these miRNAs play an important role in various cellular processes important for maintaining a healthy pregnancy, including promoting angiogenesis and the differentiation of trophoblast cells. In this review, we discuss the role of miRNAs as potential biomarkers of preeclampsia.

Severe durable changes may occur to the DNA structure caused by exogenous and endogenous risk factors initiating the process of carcinogenesis. By evidence, a large portion of malignancies have been demonstrated as being preventable. Moreover, the targeted prevention of cancer onset is possible, due to unique properties of plant bioactive compounds. Although genoprotective effects of phytochemicals have been well documented, there is an evident lack of articles which would systematically present the spectrum of anticancer effects by phytochemicals, plant extracts, and plant-derived diet applicable to stratified patient groups at the level of targeted primary (cancer development) and secondary (cancer progression and metastatic disease) prevention. Consequently, clinical implementation of knowledge accumulated in the area is still highly restricted. To stimulate coherent co-development of the dedicated plant bioactive compound investigation on one hand and comprehensive cancer preventive strategies on the other hand, the current paper highlights and deeply analyses relevant evidence available in the area. Key molecular mechanisms are presented to detail genoprotective and anticancer activities of plants and phytochemicals. Clinical implementation is discussed. Based on the presented evidence, advanced chemopreventive strategies in the context of 3P medicine are considered., Competing Interests: Conflict of interestThe authors declare that they have no conflict of interest., (© The Author(s) 2020.)

Aim: Colposcopic indexes including Reid index and Swede score were developed to make the colposcopy more objective. The aim of our study was to evaluate the significance of colposcopic indexes in the evaluation of ASC-H cervical lesions., Methods: We carried out a cross-sectional study in the Clinic of Obstetrics and Gynecology between January 2013 and December 2018. The study included 535 women, from which 66 women had a cytological result ASC-H. Scoring of all colposcopic findings was assessed according to Reid modified index and Swede score and a composite score was determined. Frequency distributions were compared using χ 2 /Fisher exact test. Spearman rank correlation coefficient was computed between RCI and Swede score., Results: Sensitivity, specificity, positive and negative predictive value and positive likelihood ratio of modified Reid colposcopic index at a cutoff of ≥4 for the detection of HSIL+ lesions were: 86.11% (95% CI: 70.5-95.3), 83.33% (95% CI: 65.3-94.4), 86.11% (95% CI: 69.7-94.8), 83.33% (95% CI: 64.5-93.7) and 5.17 (95% CI: 2.3-11.6). Swede score with the cutoff value ≥5 showed comparable results to modified Reid index with the increased sensitivity: 94.44% (95% CI: 81.3-99.3)., Conclusion: ASC-H category represents the trickiest cytological diagnosis as it is underlined with the high risk of severe cervical dysplasia. Evaluating the cervical lesion by the use of colposcopic indices helps the gynecologist to objectively evaluate all the pathologies of uterine cervix. Swede score with the cutoff value 8 also enables a 'see and treat' option in management of atypical squamous cells, cannot exclude high-grade lesions., (© 2019 Japan Society of Obstetrics and Gynecology.)

Why does healthcare of breast cancer (BC) patients, especially in a young population, matter and why are innovative strategies by predictive, preventive, and personalized medicine (PPPM) strongly recommended to replace current reactive medical approach in BC management? Permanent increase in annual numbers of new BC cases with particularly quick growth of premenopausal BC patients, an absence of clearly described risk factors for those patients, as well as established screening tools and programs represent important reasons to focus on BC in young women. Moreover, "young" BC cases are frequently "asymptomatic", difficult to diagnose, and to treat effectively on time. The objective of this article is to update the knowledge on BC in young females, its unique molecular signature, newest concepts in diagnostics and therapy, and to highlight the concepts of predictive, preventive, and personalized medicine with a well-acknowledged potential to advance the overall disease management.

Purpose: Phytochemicals are naturally occurring plant-derived compounds and some of them have the potential to serve as anticancer drugs. Based on recent evidence, aberrantly regulated expression of microRNAs (miRNAs) is closely associated with malignancy. MicroRNAs are characterized as small non-coding RNAs functioning as posttranscriptional regulators of gene expression. Accordingly, miRNAs regulate various target genes, some of which are involved in the process of carcinogenesis., Results: This comprehensive review emphasizes the anticancer potential of phytochemicals, either isolated or in combination, mediated by miRNAs. The ability to modulate the expression of miRNAs demonstrates their importance as regulators of tumorigenesis. Phytochemicals as anticancer agents targeting miRNAs are widely studied in preclinical in vitro and in vivo research. Unfortunately, their anticancer efficacy in targeting miRNAs is less investigated in clinical research., Conclusions: Significant anticancer properties of phytochemicals as regulators of miRNA expression have been proven, but more studies investigating their clinical relevance are needed.

Vaginal dryness (VD) affects both pre- and postmenopausal women at any age. Since the hormonal regulation changes during the climacteric period are considered as being the main course of the VD, affected women prefer not to talk about the problem. However, the problem does exist, and unfortunately if any, relatively minor group in the population possesses the health literacy at sufficient level to understand that VD is a suboptimal health condition which carries a multi-factorial character. Thereby, some of the contributing factors are clearly preventable and, therefore, if treated properly, have a potential to milden the VD. Current chapter demonstrates specific signs and symptoms of Flammer syndrome in women suffering from vaginal dryness, although individualised patient profiles clearly discriminate between pre- and postmenopausal women regarding the subgroup-specific symptoms. Noteworthy, about 20% of the VD patients involved in the study notify a delayed or even impaired wound healing observed for themselves over a couple of years. Optimising modifiable risk factors accompanying FS phenotype at the level of primary prevention is strongly recommended. Individualised patient profiles provide important information for VD mitigating measures tailored to the person. Further, future projects should essentially deal with the complexity of vulvar-vaginal dryness as part of the Sicca syndrome in individuals with FS phenotype, in order to prevent genital female cancers which may occur at any age. In contrast to the human papilloma virus as possible trigger of the disease, the role of the vulvar-vaginal dryness as an important risk factor is strongly underestimated in currently applied diagnostic and treatment approaches., Competing Interests: The authors declare that they have no competing interests.All subjects, who have been involved in the study, agreed to participate and signed the “informed consent” form.

The aim of our study was to evaluate GP6 gene in patients with sticky platelet syndrome (SPS) and fetal loss. Platelet aggregability was tested with platelet-rich plasma using PACKS-4 aggregometer (Helena Laboratories). High-resolution melting analysis on LightCycler 480 II (Roche Diagnostics) was used for single-nucleotide polymorphism (SNP) genotyping. We examined 64 patients with SPS and 54 control participants. We found significantly higher occurrence of 5 SNPs in patients with SPS versus controls (rs1671152, rs1654433, rs1613662, rs1654416, and rs2304167). Moreover, the haplotype analysis showed a significantly higher occurrence of 7 haplotypes in patients with SPS compared to controls (acgg and aagg in GP6_5reg haplotype; ccgt in GP6_3reg haplotype; gg and ta in GP6_REG haplotype; SKTH and PEAN in GP6_PEAN haplotype). Our results, especially higher occurrence of 4 nonsynonymous variants within the coding region, support the idea that GP6 polymorphisms are associated with the platelet hyperaggregability accompanied by fetal loss.

Chronic hypersensitivity cough syndrome affects mainly postmenopausal women; however, the pathogenesis of cough hypersensitivity in this demographic is not entirely understood. The role of sex hormones in cough has never been studied in detail; however, sex hormones seem to play an important role in the lung health of women. Our study was aimed to analyse the effect of female sex hormones (oestrogen - E2 and progesterone - Pg) on cough sensitivity measured by inhalation of capsaicin in follicular and luteal phases of menstrual cycle, characterized by significantly different concentrations of sex hormones. These data were compared with a matched group of women taking oral contraceptives. Cough sensitivity to capsaicin increased in luteal phase in subjects with normal menstrual cycle, and this functional change was not present in group with contraceptive pills. The cough sensitivity correlates with the Pg/E2 ratio, and relative lack of oestrogen in luteal phase is associated with higher cough sensitivity to capsaicin., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Preeclampsia (PE) is a pregnancy specific disease with several risk factors such as genetic polymorphisms, environmental and social factors participating in its development. The aim of this study was to investigate whether distribution of three putative regulatory SNPs rs13430086, rs5186, rs4606 in 3'UTR of genes ACVR2A, AGTR1 and RGS2, respectively, that have been associated with hypertension and regulation of trophoblast invasion differ between women with PE and control group. The associations of rs13430086, rs5186 and rs4606 with preeclampsia were tested in two groups - the group of 50 women with PE and the control group of 42 healthy pregnant women at term. DNA was isolated from blood samples and the determination of genotypes was performed using Real-Time PCR. Power analysis for the size of the cohort was performed and the results were analyzed using Fisher exact test. The AA genotype of ACVR2A rs13430086 was significantly associated with higher risk to preeclampsia compared with TT genotype (p = 0.026, OR: 5.39, 95%CI: 1.21-31.54). Results showed no association between genotypes and preeclampsia for polymorphisms rs5186, rs4606. Further studies are important in order to better understand the role of ACVR2A in the pathogenesis of PE.

Introduction: Ovarian teratomas undergo the malignant transformation in 0.2-2% of cases. The behavior of malignancies in mature cystic teratomas (MCT) is determined by their phenotype and not their derivation from germ cells. We can recognize pure angiosarcomas or as a part of other tumors like malignant mixed Mullerian tumors and adenosarcomas., Presentation of Case: We present the first case of bilateral ovarian angiosarcoma arising from the mature teratomas. Due to widespread disease, we performed limited surgical procedure consisting of bilateral adnexectomy and omentectomy. Exploratory laparotomy in 44-year old patient showed massive ascites, necrotic tissue of omentum and bilateral tumors originating from both ovaries measuring 8 and 6cm with necrotic surface. Immunohistochemistry of the tumors showed positive staining for CD31, vimentin, desmin and focal positivity for CD34., Discussion: Sarcomas of gynecologic origin are extremely rare tumors. They present with unspecified symptoms and are diagnosed in late stages of the disease. The appropriate management of angiosarcomas is difficult due to the rarity of disease and late stage of the diseases. Surgical therapy should contain the hysterectomy with bilateral salpingo-oophorectomy and omentectomy. Pelvic lymphadenectomy was not performed in published cases with no effect on patient survival., Conclusion: This work summarizes the current knowledge in the diagnosis and treatment of angiosarcomas arising in the mature teratomas. Promising results are expected from the trials devoted to antiangiogenic strategies in treatment of aggressive sarcomas., (Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Disequilibrium of hemostasis is central to the pathogenesis of all thromboses, and platelets are essential for primary hemostasis. The platelet membrane glycoprotein receptor is involved in the clot formation in blood; therefore, the changes in related genes could impair platelet aggregation in patients with sticky platelet syndrome (SPS). Patients with SPS who experienced fetal loss were shown to harbor a risk haplotype at GP6 locus. The aim of the study was to examine the genetic linkage of this selected risk haplotype with single nucleotide variations (SNVs) in the coding sequence of the GP6 gene in order to identify possible functional SNVs in association with SPS and fetal loss. A total of 37 patients with SPS manifested fetal loss, and 42 healthy controls were enrolled in the study. The SPS was diagnosed with platelet aggregometry. The SNVs were determined by dideoxy sequencing and high-resolution melting analysis. The missense variations were detected in patients with risk haplotype only. The association analysis showed association of the minor alleles with the SPS manifested by fetal loss as follows-rs1671152 (odds ratio [OR]: 4.667, 95% confidence interval [CI]: 1.462-14.89, P = .006), rs2304167 (OR: 5.085, 95% CI: 1.605-16.10, P = .003), and rs1654416 (OR: 5.085, 95% CI: 1.605-16.10, P = .003). Using the Expectation-Maximization (EM) algorithm, the estimated minor haplotype with predicted protein residue PEAN was significantly associated with the given phenotype (OR: 4.746, 95% CI: 1.486-15.15, P = .005). We have shown that haplotype PEAN associated with SPS and manifested by fetal loss and suggest that the mechanism involved in the action of GPVI has significant effect on GPVI-mediated signal transduction through Syk-phosphorylation.

The World Health Organization (WHO) defines PEComas as mesenchymal tumors composed of histologically and immunohistochemically distinctive perivascular cells. Uterus is the most common site of a subgroup of PEComas not otherwise specified(NOS). PEComas of the uterine cervix are extremely rare, and only thirteen cases have been described in the English literature to date. In this review, we summarize the available data concerning diagnostics, immunohistochemical analysis, genetics and treatment of cervical PEComas. Radical hysterectomy with bilateral salpingooophorectomy is the best surgical approach available. Adjuvant therapy in its present form is not efficient. Therefore, further studies are needed to evaluate the newest treatment strategies., (Copyright © 2016 Elsevier GmbH. All rights reserved.)

The aim of this case report is to describe a rare non-hypoxic cause of pathological changes in fetal heart rate pattern during labor, and to determine management, including a description of important prenatal aspects when pathologic cardiotocographic recording is performed during labor. A fetus with rare arteriovenous malformation of the vein of Galen, which represents less than 1% of all intracranial arteriovenous malformations, was monitored by intrapartum external cardiotocography in the 37 + 5 gestational week. The baby was born by cesarean section because of signs of imminent intrauterine hypoxia on cardiotocography. However, metabolic acidosis was not confirmed in umbilical cord blood sampling. Despite intensive neonatal care management, the newborn died 31 h after delivery because of progressive cardiac decompensation, hypotension and multi-organ failure. Precise diagnosis of the abovementioned pathology, a pre-labor plan for delivery and postnatal prognosis assessment can significantly contribute to the avoidance of a misdiagnosis of fetal hypoxia and unnecessary operative delivery with marked medico-legal consequences., (© 2015 Japan Society of Obstetrics and Gynecology.)

Objective: To bring a review of available literature sources on the prevalence of coeliac disease and its possible impact on gynecological and obstetric disorders., Design: Review article., Setting: Gynecology and Obstetrics Clinic, Jessenius Faculty of Medicine, Comenius University in Bratislava, Martin, Slovakia., Methods: Analysis of literary sources., Conclusion: Coeliac disease is an autoimmune enteropathy caused by abnormal immune system response to gluten. Over the last decade when the prevalence of the disease increases rapidly confirming the relationship between coeliac disease and a range of reproductive disorders. Problems in this area are mostly confirmed in untreated women. Among the atypical symptoms of coeliac disease also include infertility such as delayed onset of menstruation, early menopause, secondary amenorrhea, infertility and pregnancy complications, such as recurrent abortions, intrauterine fetal growth restriction, small fetus for gestational age, low birth weight and premature birth.

Introduction: Thrombophilia increases the risk of venous thrombosis during pregnancy and may predispose to gestational vascular complications., Objective: The aim of this study is to evaluate the variability of GP6 regulatory regions in a group of patients with platelet hyperaggregability manifested as miscarriage compared with control subjects., Methods: We examined 27 female patients with platelet hyperaggregability and history of spontaneous abortion and 42 healthy women. Platelet hyperaggregability was established by light transmission aggregometry. We also assessed eight SNPs within the GP6 gene., Results: We found a higher occurrence of three SNPs in patients with platelet hyperaggregability and history of miscarriage (rs1671152, rs1654433, rs1671215). The haplotype analysis showed a significant higher occurrence of two haplotypes (ACGG, CCGT)., Conclusions: Our results support the idea that genetic variability of GP6 regulatory regions can be associated with platelet hyperaggregability - a possible cause of miscarriage.

Introduction: The aim of this study was to evaluate the genetic variability of selected single nucleotide polymorphisms (SNPs) within GAS6 and PEAR1 genes and explore the association between selected SNPs and risk for fetal loss in women with sticky platelet syndrome (SPS)., Materials and Methods: We examined 23 female patients with SPS and history of spontaneous abortion, and 42 healthy women who served as controls. The diagnosis of SPS was established by light transmission aggregometry according to methods and criteria developed by Mammen et al. We also assessed four SNPs within the GAS6 gene (rs7400002, rs1803628, rs8191974, rs9550270) and two SNPs within PEAR1 gene (rs12041331, rs12566888)., Results: We identified two SNPs within PEAR1 gene (rs12041331, rs12566888) and one SNP within GAS6 gene (rs9550270) that have higher occurrence in SPS patients with history of abortion. An increased risk for abortion was observed in carriers of the rs7400002 within GAS6 gene. Conversely, we found that the T allele of PEAR1 c. -9-4663G > T polymorphism appears to be protective for fetal loss., Conclusion: Our results support the idea that genetic variability of GAS6 and PEAR1 genes may be associated with platelet hyperaggregability. The study also suggests a possible polygenic type of SPS heredity., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Objective: An overwiev of the new diagnostic method of fetal wellbeing - fetal magnetocardiography (fMCG)., Design: A review article., Setting: Department of Gynecology and Obstetrics, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Slovak Republic., Methods: An analysis of the literature using database search engines PubMed, and SCOPE in field of fMCG., Results: Fetal magnetocardiography is a non-invasive technique able to monitor the spontaneous electrophysiological activity of the fetal heart. Compared to cardiotocography and fetal electrocardiography, this is a more effective method with a higher resolution. The signal obtained from the fetal heart is sufficiently precise and the quality allows an assessment of PQRST complex alterations, and to detect fetal arrhythmia. Thanks to early diagnosis of fetal arrhythmia, there is the possibility for appropriate therapeutic intervention and the reduction of unexplained fetal death in late gestation. fMCG with high temporal resolution also increases the level of clinical trials which record fetal heart rate (FHR) variability. According to the latest theories, FHR variability is a possible indicator of fetal status and enables the study of the fetal autonomic nervous system indirectly. fMCG is an experimental method that requires expensive equipment. It is yet to be shown in the future, if this method will get any application in clinical practice.

Objective: An overwiev of the genetic aspects of pelvic floor defects and stress urinary incontinence in women., Design: A review article., Setting: Department of Gynecology and Obstetrics, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Slovak Republic., Methods: An analysis of the literature using database search engines PubMed, BLAST and Ensembl in field of POP and SUI., Results: Pelvic organ prolapse (POP) and stress urinary incontinence (SUI) affect a large number of women and often requires surgical correction. Moreover, these diseases are not only individual health but also social and economic burden on patients and society. It is possible to prevent or at least timely intervene these pathologies by screening of risk patients. The incidence of these disorders leads to find possible genetic factors. In ethiopathogenetic studies of pelvic floor defects and stress urinary incontinence it is looking for genes associated with these diseases and optimization of molecular biology methods is necessary to determine the possible gene mutations or polymorphism site. Selection of relevant genetic factors tend to clarify the pathomechanism of SUI and POP that can greatly affect their current diagnostics and therapeutics., Keywords: prolapse, stress urinary incontinence, polymorphism, gene expression.

Objective: A retrospective analysis of medical records during years 2007-2011 considers maternal and fetal outcome in patients with breech presentation terminated by vaginal delivery versus caesarean section (CS)., Design: Retrospective analysis., Setting: Department of Gynecology and Obstetrics, Jessenius Faculty of Medicine, Comenius University, Martin, Slovak Republic., Methods: Authors devided patients with breech presentation of fetus (n = 299) to groups of single pregnancies terminated in term (n = 197), before term (n = 67) and to group of multiple pregnancies (n = 35). All groups were devided according to the way of termination of pregnancy by vaginal delivery, by acute CS and by planned CS. Main followed parameters: parity, gestational week, Apgar score, birth weight, birth length, fetal gender, indications for CS, mortality and neonatal morbidity, umbilical artery pH, convulsions, admit to neonatal intensive care unit, intubation of neonate, intracranial bleeding, cervical spine and peripheral nerve injuries., Results: Total cohort of breech deliveries was 299. In the group of single pregnancies in term was 19.8% terminated by vaginal delivery (n = 39), 32.5% deliveries by acute CS (n = 64). The most common indication was fetal hypoxia (43.8%). By planned CS was terminated 47.7% deliveries (n = 94). The most common indication for CS was footling presentation (54.3%). Severe neonatal morbidity was rare and without significant difference according to the type of termination of pregnancy. Neonatal outcome was comparable in the group of preterm deliveries(n = 67) terminated by vaginal delivery or by CS. All neonatal deaths were associated with extreme prematurity and not with type of termination of gravidity., Conclusion: Clinical outcomes between vaginal breech deliveries and breech deliveries terminated by CS in term in singleton pregnancies were not significant different. Mortality of neonates delivered by preterm delivery was associated with severe prematurity.

Objective: To introduce QF-PCR method for detection of the most common chromosomal (trisomy 21, 18 and 13) and gonosomal aneuploidies at our department in the second-trimester amniotic fluid. To test the hypothesis of chromosomal aneuploidies detection using STR markers of Aneufast® kit via analysing free fetal DNA (ffDNA) isolated from plasma of pregnant women with confirmed trisomy 21 in fetus., Design: A prospective clinical study., Setting: Department of Obstetrics and Gynecology, Jessenius Faculty of Medicine and University Hospital in Martin, Slovak Republic., Methods: The samples of amniotic fluid were obtained from 67 women (twin pregnancy in 3 cases) in the 2nd trimester (15th to 22nd gestational week (g.w.)). Samples were examined using multiplex QF-PCR via Aneufast kit. In the case of positivity for trisomy 21, they were re-examined using Devyser Resolution 21 kit. All samples were parallelly evaluated by cytogenetic karyotyping. We also analyzed ffDNA from the plasma of 3 high-risk women using Aneufast kit. The plasma samples were obtained in the 2nd trimester(17th to 21st g.w.). Qiaamp DSP Virus kit was used for ffDNA isolation. Trisomy 21 of 3 fetuses was confirmed by karyotyping after 2nd trimester amniocentesis., Results: In the cohort of 70 samples, 7 pathological results (six trisomies 21 and one trisomy 18) were obtained. There was 100% concordance with cytogenetic karyotype in all samples examined by QF-PCR. The amplification of tracked chromosome 21 fragments was not evaluable in the case of ffDNA analysis., Conclusion: QF-PCR was approved as reliable, rapid, quite simple and financially bearable method of prenatal diagnostics. Despite the fact of good availability and work implementation of Aneufast® kit, results of ffDNA analysis are insufficient. We did not obtain interpretable results after ffDNA analysis from maternal plasma in trisomy 21 fetuses.

Objective: To evaluate the GP6 gene polymorphism in patients with sticky platelet syndrome (SPS) and fetal loss., Design: Genetic association study., Setting: Perinatal center., Patient(s): Twenty-seven patients with SPS, manifested as fetal loss, and 42 control subjects without SPS and no history of fetal loss and thrombosis., Intervention(s): SPS was diagnosed by platelet aggregometry (PACKS-4 aggregometer; Helena Laboratories). Seven single-nucleotide polymorphisms (SNPs) of the GP6 gene were evaluated., Main Outcome Measure(s): Occurrence of SNPs of the GP6 gene in SPS patients versus control subjects., Result(s): We found a higher occurrence of three SNPs of the GP6 gene in SPS patients versus control subjects (rs1671153: 0.204 vs. 0.048, odds ratio [OR] 5.116, 95% confidence interval [CI] 1.536-17.03; rs1654419: 0.204 vs. 0.071, OR 3.326, 95% CI 1.149-9.619; rs1613662: 0.204 vs. 0.071, OR 3.326, 95% CI 1.149-9.619). The haplotype analysis showed a significantly higher occurrence of two haplotypes (CTGAG in haplotype 5: 0.185 vs. 0.059, OR 3.568, 95% CI 1.142-11.14; and CGATAG in haplotype 6: 0.204 vs. 0.048, OR 4.961, 95% CI 1.488-16.53)., Conclusion(s): Our results, especially the higher occurrence of haplotypes CTGAG and CGATAG in SPS patients, support the idea that GP6 gene polymorphism may be associated with platelet hyperaggregability, a possible cause of fetal loss., (Copyright © 2012 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To evaluate effectiveness of electronic fetal monitoring methods during labor., Design: A case series study., Setting: Department of Gynecology and Obstetrics, Jessenius Faculty of Medicine, Comenius University, Martin, Slovak Republic., Methods: We followed 112 fetuses with simultaneous continuous monitoring (cardiotocography (CTG), intrapartal fetal pulse oxymetry (IFPO), and analysis of ST segment in fetal electrocardiogram (STAN)) during labor. We determined the effective time for every diagnostic tool., Statistics: histograms, Kolmogorov-Smirnov test, Spearman's coefficient; significance (alfa): p<0.05., Results: The effective time decreased significantly in a row: CTG > STAN > IFPO (94.8% +/- 15.1% vs. 90.4% +/- 18.3% vs. 87.4% +/- 21.2%). STAN was the most effective tool in the second stage of labor (91.3% +/- 9.4%)., Conclusion: The most effective fetal monitoring tool is CTG. However STAN is the best diagnostic method in the second stage of labor, because of its bio-signal quality.

Objective: To evaluate validity of biochemical diagnostic methods of fetal hypoxia., Design: A case-control study., Setting: Department of Gynecology and Obstetrics, Jessenius Faculty of Medicine, Comenius University, Martin, Slovak Republic., Methods: We included 67 patients, and they were retrospectively divided into group of controls (n=36), and studied group (n=31) according to pH in umbilical artery (UA) <7.15. Acid-base parameters were assessed with Rapidlab 248, Bayer Healthcare LLC, East Walpole, USA. We determined criterion for metabolic acidosis (MAC) as pH UA <7.15, resp. base deficit (BD) UA >12 mmol/l. Postpartal lactate concentration in umbilical vein (UV) and UA was determined with lactatemeter Accutrend Lactate, Roche Diagnostics, Switzerland. Quantitative assessment of fetal human protein S100B was provided with ELISA (Sangtec 100 ELISA, DiaSorin Inc., Stillwater, Minnesota, USA). Fetal erythropoietin concentration in UV was examined with immunoenzymatic assessment Access EPO (Beckman Coulter, Inc., Fullerton, CA, USA)., Statistics: histograms, Kolmogorov-Smirnov test, Mann-Whitney test, Spearman's rho; statistical significance: p<0.05, Receiver Operating Characteristic curves, Area Under the Curve., Results: The best correlation was between fetal acid-base parameters and lactate in UA (p<0.0005). Significant correlation was between EPO in UV, and protein S100B in UV (p<0.05). EPO in UV significantly correlated with lactate in UA (p<0.05). Correlation between EPO in UV and protein S100B was not significant. According to ROC curves in prediction of fetal hypoxia, we found an excellent accuracy (AUC>0.9) for lactate in UA, good accuracy (AUC>0.7) had EPO in UV. Results for protein S100B were not significant. The highest sensitivity had EPO in UV, while the highest specificity has had lactate in UA., Conclusion: An indisputable evidence of labor management quality is the fetal metabolic status. On the basis of our results, the suitable clinical markers are lactate and EPO, in addition to acid-base parameters.

Objective: To evaluate validity of biophysical diagnostic methods of fetal hypoxia., Design: A case-control study., Setting: Department of Gynecology and Obstetrics, Jessenius Faculty of Medicine, Comenius University, Martin, Slovak Republic., Methods: We divided the patients according to pH in umbilical artery (UA) < 7.15 into two groups: controls (n = 36), and studied (n = 31), retrospectively. We performed continuous simultaneous fetal monitoring with cardiotocography (CTG), fetal pulse oxymetry (IFPO), and ST segment analysis of fetal electrocardiogram (STAN)., Statistics: histograms, Kolmogorov-Smirnovov test, Mann-Whitney test, Spearman's rho; statistical significance: p < 0.05, Receiver Operating Characteristic curves, Area Under the Curve., Results: The most frequent was intermediary CTG pattern (n = 32; 47.76%). Non-reassuring IFPO was in 22 cases (32.86%), and ST events were present in 4 cases (5.97%). CTG validity in prediction of pH in UA < 7.15: sensitivity 80.0%, specificity 50.0%, positive predictive value (PPV) 22.1%, and negative predictive value (NPV) 93.4%, respectively; IFPO sensitivity was 76.3%, specificity 71.4%, PPV 32.2%, and NPV was 94.4%. Validity of STAN was not significant, because of low frequency of ST events in our study. Satisfactory accuracy (AUC > 0.8) had combined continuous monitoring with CTG, IFPO and STAN. Good accuracy (AUC > 0.7) had CTG by itself, and combined monitoring with IFPO and STAN, respectively. IFPO by itself had only sufficient accuracy (AUC > 0.6)., Conclusion: The most valid method of fetal wellbeing objectification is combined simultaneous monitoring with CTG, IFPO and STAN. Our results support the effort in the development of integrated sensor for CTG, IFPO, and STAN.

Objective: Review of actual trends in early prediction of preeclampsia., Subject: Literature review., Setting: Department of Gynecology and Obstetrics, Jessenius Faculty of Medicine, Comenius University, Martin, Slovak Republic., Subject and Method: Literature review of markers used in early prediction of preeclampsia. Review of their reliability and possible advantage of combination., Conclusion: Preeclampsia is a major cause of maternal and perinatal morbidity and mortality worldwide. Onset of clinic symptomes of preeclampsia can appear after 20 weeks of gestation. To find a single marker, or their combination, in early prediction of preeclampsia is one of the goals of modern perinatology. We look at some of the potential markers, which can fulfil these criteria.

Objective: The purpose of this study was to examine plasma levels of fibronectin and plasminogen inhibitor type 1 (PAI-1), and alterations in uterine artery (UtA) waveforms throughout normotensive and preeclamptic pregnancies and to analyze its predictive value for the detection of preeclampsia within the second trimester of pregnancy., Material and Methods: Blood samples were collected from 102 healthy, nulliparous women between the 24th and 26th gestational week. Preeclampsia developed in 13 patients; 89 normotensive control subjects were matched from the same cohort. Plasma samples were assayed for fibronectin and PAI-1 by enzyme-linked immunosorbent assay. Color pulsed Doppler examinations of UtA were performed after blood sampling. Trends were compared between two groups., Results: Maternal plasma fibronectin and PAI-1 levels and average PI, RI and S/D ratios of patients with preeclampsia were significantly higher (p< 0.05). The best cut-off values for predicting preeclampsia of fibronectin, PAI-1, PI, RI, S/D ratio based on ROC curve analysis were 290 mg/ml, 77.3 ng/ml, 1,0615, 0.605 and 2,59 respectively. The areas under the curve equal to 0.705, 0.753, 0.689, 0.695 and 0.699 for fibronectin, PAI-1 and uterine artery Doppler PI, RI, S/D ratio were determined for the prediction of preeclampsia., Conclusions: Fibronectin, PAI-1 and UtA Doppler are potentially useful predictors of preeclampsia. Maternal plasma PAI-1 combinated with fibronectin had the highest predictive values in our study.

A group of limb reduction defects is defined by congenital absence of either part of limbs. We report an extremely rare case of symmetrical upper limb peromelia (absence of distal bones) and asymmetrical lower limb phocomelia (absence of long bones and a flipper-like appearance of feet) in a female fetus at the 20th week of pregnancy. No other malformations were identified. The prevalence of peromelia and phocomelia is extremely rare, and these malformations can be associated with some candidate genes (e.g. de novo apparently balanced reciprocal translocation 46,XX,t(2;12)(p25.1;q24.1)).

Objective: To evaluate effectiveness of hormonal treatment of hyperandrogenic syndrome (HAS)., Design: Prospective randomized study., Setting: Department of Gynecology and Obstetrics, Jessenius Faculty of Medicine, Comenius University, Martin, Slovak Republic., Methods: We assessed effect of one-year-long hormonal treatment on menstrual cycles (MC), clinical signs of HAS, and ultrasound finding (USG) in 90 patients with HAS. Patients were divided into three groups with 30 females: A--35 microg ethinylestradiol (EE) with 2.0 mg cyproterone acetate/day; B--30 microg EE with 2.0 mg dienogest/day; C--30 microg EE with 3.0 mg drospirenone/day., Results: It was achieved a positive effect on MC regularity in every group during the first six months of treatment (p < 0.001). Signs of hirsutism, virilization, and USG finding were significantly better in group A., Conclusion: The most effective hormonal treatment in our study was the combination of 35 microg EE with 2.0 mg cyproterone acetate/day.

Objective: Assessment of screening and prophylaxis of streptococci group B (GBS)., Design: Retrospective study., Setting: Department of Gynecology and Obstetrics, Jessenius Faculty of Medicine, Comenius University, Martin, Slovak Republic., Methods: Groups of patients: A-GBS negative (n=601), B-GBS positive (n=166), and C-unknown GBS status (n=238)., Results: We assessed 1005 deliveries; antenatal screening was done in 767 patients (166 GBS positive). Intrapartal antibiotic prophylaxis (IAP) was the most frequent in group B (75.3%), (A-10.0%, C-15.0%). The most common antibiotics: ampicillin, and cephalosporins of the 1st and 2nd generation. The interval from rupture of membranes (ROM) to the first IAP dose was significantly the shortest in group B. The longest interval from ROM to delivery was in group A (490 min.)., Conclusion: This study shows the possibilities for improvement in GBS prophylaxis, in unknown GBS status, and preterm delivery, particularly.

Objective: Ultrasonographic evaluation of the postpartum uterus to prevent retained placental tissue complications is still a matter of debate, and it is difficult to interpret its necessity on the basis of previous studies. We hypothesized that the application of uterotonics on the basis of regular postpartum ultrasound scanning of the uterus may reduce the number of unnecessary curettages in a large unselected population., Methods: This was a cross-sectional observational study conducted among mothers (n = 6,028) delivering at two different (secondary and tertiary) hospitals to analyze the benefit of postpartum uterine ultrasound for clinical implications. Women delivering at the secondary care unit (n = 1,915) had no regular postpartum ultrasound scans in comparison to those delivering at the tertiary unit (n = 4,113). On regular ultrasound scans, morphological findings in the uterine cavity were recorded. Upon the presence of an intrauterine hyperechogenic mass larger than 2 cm in diameter, mothers received a single dose of uterotonics (methylergometrin 0.2 mg or oxytocin 5 IU) intramuscularly and control sonography after 24 h. In case of intrauterine mass persistence and serious postpartum hemorrhage women underwent a surgical intervention. The management was similar at the secondary unit, but ultrasound scans were provided only when there was a clinical finding. All patients were followed-up 6 weeks after labor., Results: Women delivering at the secondary institution experienced a higher incidence of puerperal surgical interventions (1.51 vs. 0.87%) and lower agreement between sonography and histological findings (72.4 vs. 86.1%) compared with women delivering at the tertiary care unit, respectively (P < 0.05), where the general incidence of interventions was 1.10% after spontaneous and 0.19% after cesarean deliveries. In addition, trained sonographers reached only 13.9% false-positive ultrasound scans. Time-dependent regression analysis of uterine morphological involution variables showed a significant association between uterine length, width, uterine cavity and cervical channel mass, P < 0.0001, P < 0.01, P < 0.05, P < 0.05, respectively, and insignificant association between uterine cavity volume with an increased time period postpartum., Conclusions: In this study, routine ultrasound evaluation of the uterus in the postpartum period with regular application of uterotonics decreased the rate of surgical interventions. We strongly advise the introduction of postpartum uterine scanning into obstetrical practice, most suitably provided around day 3 after delivery.

Introduction: The massive world-wide development of assisted reproduction (AR) technology and marked increase of females with infertility treatment lead to different medical complications. One of them is ovarian hyperstimulatory syndrome (OHSS), potential fatal complication in AR. It demonstrates with abdominal discomfort, nauzea, vomitus, ascites, and general alteration. It can imitate an acute abdomen syndrome, and it can lead to the primary surgical assessment., Aim: The description of OHSS as a cause of an acute abdomen syndrome., Methods: Authors present a case of OHSS with the symptomatology of acute abdomen, which was handled by surgeon, primarily., Conclusion: Consistent patient history, including gynecological history, and careful physical and laboratory examinations with relevant imaging methods lead to the elimination of invasive procedures. OHSS is the most actual in differential diagnosis of acute abdomen in fertile females for that reasons.