Management of Malignant Bowel Obstruction in Patients with Gynaecological Cancer: A Systematic Review.

Objectives: This systematic review aimed to evaluate current surgical and non-surgical management strategies for malignant bowel obstruction (MBO) in patients with gynaecological cancer. Methods: Comprehensive literature searches were conducted across MEDLINE, Embase, CENTRAL, and Scopus, without restrictions on language or publication date. Following the removal of duplicates, 4866 articles were screened, with 34 meeting the inclusion criteria. Results: Surgical intervention remains the definitive treatment for MBO, offering longer symptom-free periods and improved survival, particularly when conservative methods fail. However, the selection of surgical candidates is crucial due to the high risk of morbidity and the potential for significant complications. Non-surgical treatments, such as the use of Gastrografin, Octreotide, and Dexamethasone, along with invasive procedures like nasogastric tubing, percutaneous gastrostomy, and stent placement, offer varying degrees of symptom relief and are often considered when surgery is not feasible. Conclusions: In this article we provide a potential therapeutic algorithm for the management of patients with MBO. This review underscores the urgent need for high-quality research to develop clear, evidence-based guidelines for MBO management in patients with gynaecologic cancer. Establishing standardised protocols will improve patient outcomes by aiding clinicians in making informed, individualised treatment decisions.

Comprehensive Evaluation of a Levonorgestrel Intrauterine Device (LNG-IUD), Metformin, and Liraglutide for Fertility Preservation in Endometrial Cancer: Protocol for a Randomized Clinical Trial.

Endometrial cancer is a leading gynecological malignancy, with obesity being a significant risk factor due to increased estrogen production in body fat. Current treatments often involve hysterectomy, which precludes fertility, thus highlighting the need for fertility-preserving options. This study aims to evaluate the combined efficacy of a levonorgestrel intrauterine device (LNG-IUD), metformin, and liraglutide for treating women with endometrial hyperplasia or early stage endometrial cancer while preserving fertility. The study will enroll 264 women aged 18-45 with a BMI > 30 who desire uterine preservation. Participants will be randomized into three groups: LNG-IUD alone, LNG-IUD plus metformin, and LNG-IUD plus metformin and liraglutide. Primary outcomes will include complete pathological remission, while secondary outcomes will assess histological changes, glucose, insulin levels, and weight changes over a 12-month period. This study protocol hypothesizes that LNG-IUD combined with metformin and liraglutide may potentially lead to higher regression rates of endometrial hyperplasia (EH) and early stage endometrial cancer (EC) compared to LNG-IUD alone. Furthermore, the protocol anticipates that these combination therapies will demonstrate good tolerability with minimal adverse effects, suggesting the potential benefit of integrating metabolic interventions with LNG-IUD to enhance treatment efficacy while preserving fertility in women with EH and EC.

Sociodemographic and Medical Characteristics of Women Applied for Emergency Contraception-A Retrospective Observational Study.

Background: Lifestyle factors significantly impact overall health. Our aim was to assess reproductive health awareness among patients who applied for emergency contraceptive pills. Methods: This present retrospective observational study between July 2021 and September 2021 is embedded in the MEEC (Motivation and Epidemiology of Emergency Contraceptive Pill) based on the study cohort of a Hungarian data bank containing follow-up data of 447 women who applied for EC telemedicine consultation. Collected data: age, history of previous pregnancy, lifestyle factors like smoking, alcohol consumption, sexual characteristics: partner consistency and protection during intercourse, cervical cancer screening within the past 2 years, previous HPV screening, and the preference for future contraceptive methods. The investigation also compiled accurate data on intercourse (elapsed time to request a medical consultation). Lifestyle factors were scored. Results: The more health-conscious patients were quicker to report for a post-event pill. Earlier pregnancies and older age were associated with greater reproductive health awareness. Conclusions: Reproductive health awareness is increased by previous pregnancies and older age. More health-conscious women consult a doctor earlier, which can reduce the chance of various health damage. Our study emphasizes the significance of lifestyle factor influence on reproductive health decisions.

SHBG Levels Do Not Correlate with Insulin Levels in PCOS with Appropriate Fasting Insulin Sensitivity.

Introduction: There are several phenotypes of polycystic ovarian syndrome (PCOS), and the different phenotypes may differ metabolically. Methods: In the present retrospective study, women with PCOS having normal fasting insulin sensitivity (n = 88) were compared with women with PCOS showing impaired insulin sensitivity (n = 46) using the HPCOS (Hungarian Polycystic ovarian syndrome) database. Results: The impaired insulin sensitivity group has significantly higher body mass index (BMI) and HOMA index than the normal fasting insulin sensitivity group (BMI (kg/m2): 22.0 vs. 28.1, p < 0.0001, HOMA index: 0.96 vs. 2.38, p < 0.0001). The sex hormone binding globulin (SHBG) level was significantly lower, and the free androgen index proved itself significantly higher in the impaired insulin sensitivity group (p < 0.05). Linear regression analysis showed a negative association of BMI with SHBG levels in both groups, while BMI had a positive correlation with insulin concentrations in both groups. However, the SHBG levels were negatively associated with insulin concentrations in the impaired insulin sensitivity group, but this inverse association could not be observed in the normal fasting insulin sensitivity group. Conclusions: The inverse linear correlation of SHBG with HOMA index and serum insulin level is not evident in all PCO syndrome phenotypes, thus SHBG has limited applicability for characterizing carbohydrate metabolism and serum insulin sensitivity.

Motivators for emergency contraception: Previous pregnancy and condom rupture.

Objectives: Little is known about the motivations to apply for emergency contraception (EC). Our first aim was to explore the motivating circumstances to use EC as fast as possible. Our second aim was to explore the contraceptive method of the population seeking EC. Study design: This present retrospective observational study between July 2021 and September 2021 is embedded in the MEEC (Motivation and Epidemiology of Emergency Contraceptive Pill) based on the study cohort of a Hungarian data bank containing follow-up data of 455 women applied for EC telemedicine consultation. Variables assessed were: age, gynecological history (pregnancies, abortions, miscarriages), data of the intercourse (elapsed time, contraceptive method), and data of the menstrual cycle, and relationship status. Results: Of all patients, 59.3 % reported condom rupture, 29.5 % no protection, and 11.2 % other. Patients using condom applied for EC significantly sooner than those using no protection and using other protective methods. A significantly shorter elapsed time was observed in patients with a history of a previous pregnancy. No significant relationship was seen between the way of protection, previous pregnancies, and surprisingly the time of ovulation despite the obvious intention of avoiding pregnancy. Conclusions: This is the first study to examine the potential role of epidemiologic factors as motivators for EC on the basis of a large patient cohort. Our study demonstrates the significant role of condom rupture/use and the history of previous pregnancies to be the strongest motivators for EC.

Effects of Gender and Vitamin D on Vascular Reactivity of the Carotid Artery on a Testosterone-Induced PCOS Model.

The negative cardiovascular effects of polycystic ovary syndrome (PCOS) and vitamin D deficiency (VDD) have been discussed previously; however, the sex differences between PCOS females and males are not yet known. Our aim was to investigate the effect of PCOS and VDD in the carotid artery of male and female Wistar rats. Females were treated with transdermal testosterone (Androgel) for 8 weeks, which caused PCOS. VDD and vitamin D supplementation were accomplished via diet. The carotid arteries' contraction and relaxation were examined using myography. Receptor density was investigated using immunohistochemistry. In PCOS females, angiotensin receptor density, angiotensin II-induced contraction, androgen receptor optical density, and testosterone-induced relaxation increased. The increased contractile response may increase cardiovascular vulnerability in women with PCOS. As an effect of VDD, estrogen receptor density increased in all our groups, which probably compensated for the reduced relaxation caused by VDD. Testosterone-induced relaxation was decreased as a result of VDD in males and non-PCOS females, whereas this reduction was absent in PCOS females. Male sex is associated with increased contraction ability compared with non-PCOS and PCOS females. VDD and Androgel treatment show significant gender differences in their effects on carotid artery reactivity. Both VDD and PCOS result in a dysfunctional vascular response, which can contribute to cardiovascular diseases.

A Novel Dual-Function Nitric Oxide Donor Therapy for Preeclampsia-A Proof-of-Principle Study in a Murine Model.

Background: Preeclampsia (PE) is a hypertensive disorder of pregnancy that is associated with substantial morbidity and mortality for the mother and fetus. Reduced nitric oxide bioavailability and oxidative stress contribute to the maternal and fetal pathophysiology of PE. In this study, we evaluated the efficacy of a novel dual-function nitric oxide donor/redox modulator, AKT-1005, in reducing PE symptoms in a mouse model of PE. Method: The potential therapeutic effect of AKT-1005 was tested in an animal model of Ad.sFlt-1-induced hypertension, proteinuria and glomerular endotheliosis, a model of PE. Pregnant Ad.sFlt-1-overexpressing CD1 mice were randomized into groups administered AKT-1005 (20 mg/kg) or a vehicle using a minipump on gd11 of pregnancy, and the impact on blood pressure and renal and placental damage were assessed. Results: In healthy female mice, ex vivo treatment of resistance vessels with AKT-1005 induced vasorelaxation, and 6 days of treatment in vivo did not significantly alter blood pressure with or without pregnancy. When given for 6 days during pregnancy along with Ad.sFlt-1-induced PE, AKT-1005 significantly increased plasma nitrate levels and reduced hypertension, renal endotheliosis and plasma cystatin C. In the placenta, AKT-1005 improved placental function, with reduced oxidative stress and increased endothelial angiogenesis, as measured by CD31 staining. As such, AKT-1005 treatment attenuated the Ad.sFlt-1-induced increase in placental and free plasma soluble endoglin expression. Conclusions: These data suggest that AKT-1005 significantly attenuates the sFlt-1-induced PE phenotypes by inhibiting oxidative stress, the anti-angiogenic response, and increasing NO bioavailability. Additional research is warranted to investigate the role of AKT-1005 as a novel therapeutic agent for vascular disorders such as preeclampsia.

[Emergency contraception.] / Esemény utáni fogamzásgátlás.

INTRODUCTION: Emergency contraception is an effective and safe solution for preventing unwanted pregnancies. Many methods of emergency contraception are used, which have different mechanisms of action and time frames. OBJECTIVE: Providing information to healthcare professionals and decision-makers based on the literature data about the target populations of emergency contraception, evidence-based modern methods, their effectiveness, and practical application for the purpose of reducing the incidence of unintended pregnancies. METHODS: We conducted a systematic literature search in MEDLINE (PubMed), Embase and Scopus databases based on relevant keywords, for publications that were published between 1960 and 2023. RESULTS: 23 clinical professional publications were selected that examined the effectiveness of oral and long-term usable contraceptives as emergency contraceptives. Our research results were interpreted in terms of weight, breastfeeding, time elapsed since the intercourse and future contraceptive plans, which help to select the most appropriate emergency contraceptive for healthcare professionals. CONCLUSION: Based on the literature data, our systematic review provides assistance for choosing between the available oral levonorgestrel, ulipristal acetate, and intrauterine contraceptive devices available in Hungary based on effectiveness, target population, and accessibility. We support the healthcare governance in creating up-to-date professional guidelines to improve the availability of emergency contraception and, consequently, enhance reproductive health. Orv Hetil. 2023; 164(44): 1736-1748.

A Novel Dual-Function Redox Modulator Relieves Oxidative Stress and Anti-Angiogenic Response in Placental Villus Explant Exposed to Hypoxia-Relevance for Preeclampsia Therapy.

BACKGROUND: Preeclampsia (PE) is a severe, life-threatening complication during pregnancy (~5-7%), and no causative treatment is available. Early aberrant spiral artery remodeling is associated with placental stress and the release of oxygen radicals and other reactive oxygen species (ROS) in the placenta. This precedes the production of anti-angiogenic factors, which ultimately leads to endothelial and trophoblast damage and the key features of PE. We tested whether a novel dual-function redox modulator-AKT-1005-can effectively reduce placental oxidative stress and alleviate PE symptoms in vitro. METHOD: Isolated human villous explants were exposed to hypoxia and assessed to determine whether improving cell-redox function with AKT-1005 diminished ROS production, mitochondrial stress, production of the transcription factor HIF1A, and downstream anti-angiogenic responses (i.e., sFLT1, sEng production). MitoTEMPO was used as a reference antioxidant. RESULTS: In our villous explant assays, pretreatment with AKT-1005 reduced mitochondrial-derived ROS production, reduced HIF-1A, sFLT1, and sEng protein expression, while increasing VEGF in hypoxia-exposed villous trophoblast cells, with better efficiency than MitoTEMPO. In addition, AKT-1005 improved mitochondrial electron chain enzyme activity in the stressed explant culture. CONCLUSIONS: The redox modulator AKT-1005 has the potential to intervene with oxidative stress and can be efficacious for PE therapy. Future studies are underway to assess the in vivo efficacy of HMP.

Nitroxide-HMP-Protects Human Trophoblast HTR-8/SVneo Cells from H2O2-Induced Oxidative Stress by Reducing the HIF1A Signaling Pathway.

Preeclampsia (PE) is a pregnancy-specific syndrome affecting 5-7% of patients. There is no effective treatment available. Early abnormal placental development is associated with oxidative stress (OS) and a release of reactive oxygen species (ROS) in the placenta. This phenomenon leads to downstream signaling, Hypoxia Inducible Factor 1A (HIF1A) stabilization and transcription of the anti-angiogenic factors soluble fms-like tyrosine kinase 1 (sFLT1) and soluble endoglin (sEng), which are known to cause endothelial and trophoblast dysfunction and cardinal features of PE: hypertension, proteinuria and, in severe cases, eclampsia. We tested whether 3-(Hydroxymethyl)-1-oxy-2,2,5,5-tetramethylpyrrolidine (HMP)-a nitroxide-type antioxidant molecule-can reduce placental OS and mitigate PE symptoms in vitro. We induced OS in human trophoblast (HTR-8/SVneo) cells with hydrogen peroxide (H2O2) and assessed whether modulating cell redox function with HMP reduces cell injury, mitochondrial stress and HIF1A and sFLT1 production. Pre-treatment with HMP reduced mitochondrial-derived ROS production, restored LC3B expression and reduced HIF1A and sFLT1 expression in H2O2-exposed HTR-8/SVneo trophoblast cells. HMP improved the mitochondrial electron chain enzyme activity, indicating that a reduction in OS alleviates mitochondrial stress and also reduces anti-angiogenic responses. In reducing placental trophoblast OS, HMP presents a potential novel therapeutic approach for the treatment of PE. Future investigation is warranted regarding the in vivo use of HMP.

[Herniated amniotic sac through uterine dehiscence at the 30th gestational week after prior laparoscopic salpingectomy]. / Elozetes laparoszkópos salpingectomiát követo hegszétválás és buroksérv a várandósság 30. hetében.

Uterine rupture is a rare complication during pregnancy which may even lead to the death of the mother and the fetus. In this report, the management of a herniated amniotic sac associated with uterine dehiscence is presented. A 25-year-old primigravida at 30 weeks with a history of a previous unilateral salpingectomy was transferred to our hospital with the potential diagnosis of a herniated amniotic sac, which was discovered during a routine ultrasound scan. The patient had no prior complaints or any other signs that would have indicated a serious condition during her pregnancy. She underwent an emergency cesarean section and a two-layer closure of the lesion. An adequate suture during laparoscopic salpingectomy provides prevention of uterine rupture during subsequent pregnancies. A medical history with a previous laparoscopic dehiscence should necessitate a more frequent sonographic observation during pregnancy. Orv Hetil. 2023; 164(25): 988-992.

Risk Estimation of Gestational Diabetes Mellitus in the First Trimester.

CONTEXT: There is no early, first-trimester risk estimation available to predict later (gestational week 24-28) gestational diabetes mellitus (GDM); however, it would be beneficial to start an early treatment to prevent the development of complications. OBJECTIVE: We aimed to identify early, first-trimester prediction markers for GDM. METHODS: The present case-control study is based on the study cohort of a Hungarian biobank containing biological samples and follow-up data from 2545 pregnant women. Oxidative-nitrative stress-related parameters, steroid hormone, and metabolite levels were measured in the serum/plasma samples collected at the end of the first trimester from 55 randomly selected control and 55 women who developed GDM later. RESULTS: Pregnant women who developed GDM later during the pregnancy were older and had higher body mass index. The following parameters showed higher concentration in their serum/plasma samples: fructosamine, total antioxidant capacity, testosterone, cortisone, 21-deoxycortisol; soluble urokinase plasminogen activator receptor, dehydroepiandrosterone sulfate, dihydrotestosterone, cortisol, and 11-deoxycorticosterone levels were lower. Analyzing these variables using a forward stepwise multivariate logistic regression model, we established a GDM prediction model with a specificity of 96.6% and sensitivity of 97.5% (included variables: fructosamine, cortisol, cortisone, 11-deoxycorticosterone, SuPAR). CONCLUSION: Based on these measurements, we accurately predict the development of later-onset GDM (24th-28th weeks of pregnancy). Early risk estimation provides the opportunity for targeted prevention and the timely treatment of GDM. Prevention and slowing the progression of GDM result in a lower lifelong metabolic risk for both mother and offspring.

Impact of Sex and Exercise on Femoral Artery Function: More Favorable Adaptation in Male Rats.

Blood flow increases in arteries of the skeletal muscles involved in active work. Our aim was to investigate the gender differences as a result of adaptation to sport in the femoral arteries. Vascular reactivity and histology of animals were compared following a 12-week swimming training. Animals were divided into sedentary male (MS), trained male (MTr), sedentary female (FS), and trained female (FTr) groups. Isolated femoral artery rings were examined by wire myography. Contraction induced by phenylephrine (Phe) did not differ between the four groups. The contractile ability in the presence of indomethacin (INDO) was decreased in both sedentary groups. However, we found a specific cyclooxygenase-2 (COX-2) role only in FS rats. After exercise training, we observed increased vasoconstriction in both sexes, when nitro-L-arginine methyl ester (L-NAME) was present. The COX-dependent vasoconstriction effect disappeared in MTr animals, and the COX-2-dependent vasoconstriction effect disappeared in FTr ones. Relaxation was reduced significantly, when L-NAME was present in MTr animals compared to in FTr rats. The training was associated with greater endothelial nitric oxide synthase (eNOS) protein expression in males, but not in females. The present study proves that there are gender differences regarding adaptation mechanisms of musculocutaneous arteries to sports training. In males, relaxation reserve capacity was markedly elevated compared to in females.

[Molar pregnancy in postmenopause]. / Molaterhesség postmenopausában.

Hydatidiform mole is an extremely rare gestational trophoblastic disease. The pathogenesis is unique in that the maternal tumor arises from pregnancy tissue. In terms of occurrence, it mainly affects women of reproductive age. In our case report, a 53-year-old female patient was diagnosed with molar pregnancy as the background of her perimenopausal bleeding disorder. Mola is a high-risk disease because the symptoms can be deceiving and may be very similar to those of an incomplete miscarriage, ectopic pregnancy or perimenopausal bleeding. Appropriate diagnosis is key to terminating the pregnancy as soon as possible. The purpose of our case report is to draw attention to the atypical appearance of molar pregnancy; in relation to our perimenopausal female patient, we review the basic principles of treatment of hydatidiform mole and present the diagnostic and therapeutic management of a successfully completed case. Orv Hetil. 2023; 164(7): 273-277.

Structural Features of Small Molecule Antioxidants and Strategic Modifications to Improve Potential Bioactivity.

This review surveys the major structural features in various groups of small molecules that are considered to be antioxidants, including natural and synthetic compounds alike. Recent advances in the strategic modification of known small molecule antioxidants are also described. The highlight is placed on changing major physicochemical parameters, including log p, bond dissociation energy, ionization potential, and others which result in improved antioxidant activity.

The Importance of Nutrition in Menopause and Perimenopause-A Review.

Menopause is associated with an increased prevalence of obesity, metabolic syndrome, cardiovascular diseases, and osteoporosis. These diseases and unfavorable laboratory values, which are characteristic of this period in women, can be significantly improved by eliminating and reducing dietary risk factors. Changing dietary habits during perimenopause is most effectively achieved through nutrition counseling and intervention. To reduce the risk factors of all these diseases, and in the case of an already existing disease, dietary therapy led by a dietitian should be an integral part of the treatment. The following review summarizes the recommendations for a balanced diet and fluid intake, the dietary prevention of cardiovascular diseases, the role of sleep, and the key preventive nutrients in menopause, such as vitamin D, calcium, vitamin C, B vitamins, and protein intake. In summary, during the period of perimenopause and menopause, many lifestyle factors can reduce the risk of developing all the diseases (cardiovascular disease, insulin resistance, type 2 diabetes mellitus, osteoporosis, and tumors) and symptoms characteristic of this period.

Additive damage in the thromboxane related vasoconstriction and bradykinin relaxation of intramural coronary resistance arterioles in a rodent model of andropausal hypertension.

Hypertension and andropause both accelerate age-related vascular deterioration. We aimed to evaluate the effects of angiotensin-II induced hypertension and deficiency of testosterone combined regarding the resistance coronaries found intramurally. Four male groups were formed from the animals: control group (Co, n = 10); the group that underwenr orchidectomy (ORC, n = 13), those that received an infusion of angiotensin-II (AII, n = 10) and a grous that received AII infusion and were also surgically orchidectomized (AII + ORC, n = 8). AII and AII + ORC animals were infused with infusing angiotensin-II (100 ng/min/kg) using osmotic minipumps. Orchidectomy was perfomed in the ORC and the AII + ORC groupsto establish deficiency regarding testosterone. Following four weeks of treatment, pressure-arteriography was performed in vitro, and the tone induced by administration of thromboxane-agonist (U46619) and bradykinin during analysis of the intramural coronaries (well-known to be resistance arterioles) was studied. U46619-induced vasoconstriction poved to be significantly decreased in the ORC and AII + ORC groups when compared with Co and AII animals. In ORC and AII + ORC groups, the bradykinin-induced relaxation was also significantly reduced to a greater extent compared to Co and AII rats. Following orchidectomy, the vasocontraction and vasodilatation capacity of blood vessels is reduced. The effect of testosterone deficiency on constrictor tone and relaxation remains pronounced even in AII hypertension: testosterone deficiency further narrows adaptation range in the double noxa (AII + ORC) group. Our studies suggest that vascular changes caused by high blood pressure and testosterone deficiency together may significantly increase age-related cardiovascular risk.

Vitamin-D Deficiency and Supplementation Altered the Network of the Coronary Arteries in a Rodent Model-In Situ Video Microscopic Technique.

The aim of our study was to identify whether vitamin-D deficiency (VDD) can alter the geometry of the coronary-resistance-artery system. Male Wistar rats were divided into vitamin-D-deficient (VD-, n = 10) and vitamin-D-supplemented (VD+, n = 8) groups. After eight weeks, branches and segments of the left-anterior-descending-coronary-artery (LAD) network were analyzed by a video-microscopy technique. Segments were divided into 50 µm-long cylindrical ring units. VDD did not increase the number of morphological abnormalities. The number of segments did not differ between the groups (VD-: 210 and VD+: 224; pooled data of 8 networks). A larger lumen area of branches was found in VD+ group, while 1-4-order branches were lengthier in the VD- group. VD- rats had less rich coronary-resistance-artery networks in terms of 50 µm-long units. (VD-: 6365 vs. VD+: 6602; pooled data of 8 networks). VD+ animals were richer in the 100-350 µm outer diameter range, and VD- animals were richer in the 400-550 µm-diameter units. In VD- rats, 150-200 and 300 µm units were almost missing at higher flow distances from the orifice. Serum vitamin-D alterations caused by dietary changes can affect the geometry of the coronary-artery network, which may contribute to vitamin-D-dependent changes in cardiovascular mortality.

Effects of Vitamin D on Fertility, Pregnancy and Polycystic Ovary Syndrome-A Review.

Polycystic ovary syndrome (PCOS) is one of the most common endocrine reproductive disorders in women. Vitamin D deficiency is also quite common in this condition. The degree of vitamin D deficiency correlates with the severity of PCOS. Both male and female vitamin D levels play a role in fertility and affect the outcomes of in vitro fertilization (IVF). Moreover, fertility and IVF indicators are improved by vitamin D not only in healthy women but in those diagnosed with PCOS. Both vitamin D deficiency and PCOS increase pregnancy-related complications. Vitamin D supplementation and optimal vitamin D levels decrease both maternal and fetal risk for complications and adverse events. Furthermore, vitamin D supplementation may ameliorate or even prevent pregnancy-related reversible bone loss in mothers. This review emphasizes the roles of vitamin D deficiency and vitamin D supplementation and their correlation with PCOS regarding reproductive health.