Cervical Cancer Mortality in Romania: Trends, Regional and Rural-Urban Inequalities, and Policy Implications.

Background and Objectives: Despite being largely preventable, cervical cancer mortality still remains an important public health problem globally, in Europe, and in Romania. The European Union member states are urged to implement systematic, population-based screenings for cervical cancer, but the programs developed by the countries remain very heterogeneous. This study aimed to investigate the differences in cervix cancer mortality between Romania and EU and within Romania over the last two decades and to reveal the major sources of inequalities and the policy implications. Materials and Methods: We analyzed the number of deaths and the mortality rates by cervical cancer, standardized using the direct method, over two decades (2001-2016 for the EU, and 2001-2019 for the national and sub-national analyses). Trends, mortality reduction over the years, and mortality differences at the beginning and end of the time interval have been calculated for the EU and Romania, at national and sub-national levels (rural-urban and regions). Results: Our results revealed differences in cervical cancer mortality between Romania and EU and within Romania (among regions and rural-urban areas). These differences used to be very high in the past and are still persisting. Conclusions: The country should revisit its national cervical cancer screening program, which has been implemented for many years, but with a very limited participation rate. Due to the similar problems existing in Central-Eastern Europe, targeted support from the EU for the members from this geographical area could contribute to the minimization of differences in cervical cancer mortality among the EU members.

Emerging Therapeutic Concepts and Latest Diagnostic Advancements Regarding Neuroendocrine Tumors of the Gynecologic Tract.

Neuroendocrine neoplasms (NENs) are particularly rare in all sites of the gynecological tract and include a variety of neoplasms with variable prognosis, dependent on histologic subtype and site of origin. Following the expert consensus proposal of the International Agency for Research on Cancer (IARC), the approach in the latest World Health Organization (WHO) Classification System of the Female Genital Tumours is to use the same terminology for NENs at all body sites. The main concept of this novel classification framework is to align it to all other body sites and make a clear distinction between well-differentiated neuroendocrine tumors (NETs) and poorly differentiated neuroendocrine carcinomas (NECs). The previous WHO Classification System of the Female Genital Tumours featured more or less the same principle, but used the terms 'low-grade neuroendocrine tumor' and 'high-grade neuroendocrine carcinoma'. Regardless of the terminology used, each of these two main categories include two distinct morphological subtypes: NETs are represented by typical and atypical carcinoid and NEC are represented by small cell neuroendocrine carcinoma (SCNEC) and large cell neuroendocrine carcinoma (LCNEC). High-grade NECs, especially small cell neuroendocrine carcinoma tends to be more frequent in the uterine cervix, followed by the endometrium, while low-grade NETs usually occur in the ovary. NENs of the vulva, vagina and fallopian tube are exceptionally rare, with scattered case reports in the scientific literature.

Navigating Fertility Preservation Options in Gynecological Cancers: A Comprehensive Review.

(1) Background: Currently, an increasing number of women postpone pregnancy beyond the age of 35. Gynecological cancers affect a significant proportion of women of reproductive age, necessitating the development of fertility preservation methods to fulfill family planning. Consequently, providing treatment options that preserve fertility in women diagnosed with gynecological cancers has become a crucial component of care for survivors. (2) Methods: We conducted an extensive search of relevant scientific publications in PubMed and Embase databases and performed a narrative review, including high-quality peer-reviewed research on fertility after being treated for gynecologic cancers, reporting pregnancy rates, birth rates, and pregnancy outcomes in cancer survivors as well as therapeutic options which partially preserve fertility and methods for obtaining a pregnancy in survivors. (3) Discussion: The medicine practiced today is focused on both treating the neoplasm and preserving the quality of life of the patients, with fertility preservation being an important element of this quality. This leads to an improved quality of life, allowing these women to become mothers even in the seemingly adverse circumstances posed by such a pathology. However, although there are guidelines on female fertility preservation in the context of neoplasms, an analysis shows that physicians do not routinely consider it and do not discuss these options with their patients. (4) Conclusions: Advancements in medicine have led to a better understanding and management of gynecological neoplasms, resulting in increased survival rates. Once the battle against these neoplasms is won, the issue of preserving the quality of life for these women arises, with fertility preservation being an important aspect for women who have not yet fulfilled their family planning desires at the time of diagnosis. It is important for patients to be informed about the available options for fertility preservation and to be encouraged to make informed decisions in collaboration with their medical team. Standardized recommendations for onco-fertility into guidelines should be taken into consideration in the future.

Respiratory Follow Up of the Premature Neonates-Rationale and Practical Issues.

The aim of the review was to present the state of knowledge about the respiratory pathology in former premature neonates (children that were born preterm-before 37 weeks of gestation-and are examined and evaluated after 40 weeks corrected age) other than chronic lung disease, in order to provide reasons for a respiratory follow-up program for this category of patients. After a search of the current evidence, we found that premature infants are prone to long-term respiratory consequences due to several reasons: development of the lung outside of the uterus, leading to dysmaturation of the structures, pulmonary pathology due to immaturity, infectious agents or mechanical ventilation and deficient control of breathing. The medium- to long-term respiratory consequences of being born before term are represented by an increased risk of respiratory infections (especially viral) during the first years of life, a risk of recurrent wheezing and asthma and a decrease in pulmonary volumes and airway flows. Late preterm infants have risks of pulmonary long-term consequences similar to other former premature infants. Due to all the above risks, premature neonates should be followed in an organized fashion, being examined at regular time intervals from discharge from the maternity hospital until adulthood-this could lead to an early detection of the risks and preventive therapies in order to improve their prognosis and assure a normal and productive life. The difficulties related to establishing such programs are represented by the insufficient standardization of the data gathering forms, clinical examinations and lung function tests, but it is our belief that if more premature infants are followed, the experience will allow standards to be established in these fields and the methods of data gathering and evaluation to be unified.

Antioxidants in Hops: Bioavailability, Health Effects and Perspectives for New Products.

Hop plant (Humulus lupulus L.) has been used by humans for ages, presumably first as a herbal remedy, then in the manufacturing of different products, from which beer is the most largely consumed. Female hops cones have different useful chemical compounds, an important class being antioxidants, mainly polyphenols. This narrative review describes the main antioxidants in hops, their bioavailability and biological effects, and the results obtained by now in the primary and secondary prevention of several non-communicable diseases, such as the metabolic syndrome related diseases and oncology. This article presents in vitro and in vivo data in order to better understand what was accomplished in terms of knowledge and practice, and what needs to be clarified by additional studies, mainly regarding xantohumol and its derivates, as well as regarding the bitter acids of hops. The multiple protective effects found by different studies are hindered up to now by the low bioavailability of some of the main antioxidants in hops. However, there are new promising products with important health effects and perspectives of use as food supplements, in a market where consumers increasingly search for products originating directly from plants.

Endometrial polyps.

Endometrial polyps (EPs) are a frequent gynecological condition. EPs often arise in the common womanly patients and are appraised to be about 25%. Advancing age, hyperestrogenism, hypertension, and Tamoxifen use are acknowledged as ordinary risk elements for the development of EP. The etiopathogenesis of EP is not accurately elucidated, but certain considerations such as diabetes mellitus, hormonal factors or arterial hypertension are considered to perform a significant contribution. The diagnosis of EPs is essentially by imaging. Transvaginal ultrasound is the primary investigation in EPs. Hysteroscopic resection is now the "gold standard" to treat to treat this disease. Hysterectomy is the definitive treatment for EPs, but it requires a judicious indication and an adequate counseling of the patient. Currently, a certain histological pattern is found in different sequences in EPs. Even if the vast majority EPs are benign, they may reach hyperplastic, with malignant alteration. The purpose of this pictorial review is the integrated approach to this type of abnormal endometrial proliferation from the perspective of natural history, diagnosis, management, morphological aspects, risk of malignancy, recurrence and last but not least, clinical outcome.

Polycythemia vera in pregnancy represents a challenge for a multidisciplinary collaboration: A case report and literature review.

Polycythemia vera (PV) is a rare chronic myeloproliferative neoplasm which represents an additional thrombotic factor in pregnancy. PV may be difficult to diagnose, particularly as its incidence is extremely uncommon among young women. The main diagnostic method involves a bone marrow biopsy, and high hemoglobin and platelet counts are usually indicative of the condition, after excluding other more frequent pathologies. PV is associated with a high risk of thrombosis, particularly in pregnancy, and requires anti-platelet treatment. At present, only a limited number of PV cases in pregnancy have been reported in the literature, at least to the best of our knowledge, with the largest case series being a retrospective study that included 25 pregnancies in 15 women. The present study describes the case of a patient diagnosed with JAK2-positive PV and also discusses this rare condition with particular focus on the following: i) The management of PV in pregnancy along with the additional pathologies in this specific case; and ii) the particularities of the pregnancy course. By identifying women suffering from PV superimposed by other possible procoagulant factors and applying the latest standard in healthcare, fetal and maternal prognosis may be significantly improved.

Influence of pemphigoid gestationis on pregnancy outcome: A case report and review of the literature.

Pemphigoid gestationis is considered to be a rare pregnancy exclusive bullous disease, which modifies the course of the pregnancy, with difficulties in the management of the pruritus and skin lesions as well as a possible change in the neonatal outcome. Differential diagnosis of skin lesions and pruritus in pregnancy is challenging, and complementary investigations such as skin biopsy or laboratory tests are indispensable. The correct diagnosis and proper treatment could change the natural course of a pregnancy at risk and could improve maternal and fetal morbidity. We present the case of a patient with pemfigoid gestationis with the aim to highlight: i) the management of this pregnancy-associated skin disorder which transfers this pregnancy into a category of high obstetrical risk pregnancy; ii) the particularities of the course of the pregnancy; and iii) the importance in the differential diagnosis of pregnancy dermatoses. The particularity of this case of pemphigoid gestationis was the acute fetal distress in the absence of intrauterine growth restriction that is frequently found in this pathology, and the management of a rare pregnancy skin condition that currently has no standard treatment.

Success rate of methotrexate in the conservative treatment of tubal ectopic pregnancies.

An ectopic pregnancy (EP) involves the implantation of the gestational sac outside the uterine cavity. In the event of diagnosing an EP, the current medical approach is to avoid surgery and to preserve fertility whenever possible; therefore, methotrexate (MTX)-based therapy has become prominent in recent years. MTX, a drug usually used to treat severe forms of autoimmune diseases and several types of cancer, has proven its utility in the conservative treatment of EPs. The success rate of MTX correlates with lower values of ß subunit of human chorionic gonadotropin hormone (ß-hCG) serum levels, especially below 2,000 mUI/ml, side effects being insignificant. In the present study, the results obtained concerning the success rate of MTX in the conservative treatment of EPs were obtained at the Department of Obstetrics and Gynecology of the Bucharest University Emergency Hospital from January 2014 to December 2020. The aim of the present study was to highlight the necessity for revising current guidelines for ectopic pregnancy medical treatment in order to manage this pathology optimally and to select carefully the proper treatment, whether medical, surgical or expectant management, so that morbidity is reduced to a minimum.

A Systematic Approach of the Intrauterine Morphogenesis of the Human Palpebral Apparatus.

The human eyelid embodies a vast diversity of functions. Acting as a protective shield for the ocular apparatus and as a light regulator in the sight process, eyelids stand a fascinating - yet omitted - role in facial aesthetics, serving as a racial trait by which humankind succeeded to manifest heterogeneity as a species. These assumptions are precisely forecasted right from in-utero life through intricate processes of growth and cell differentiation. In the Department of Anatomy of "Carol Davila" University of Medicine and Pharmacy, we performed morphological assessments on 41 embryos and fetuses with gestational ages ranging from 6 to 29 weeks. This study aims to illustrate the morphogenesis of eyelids in human embryos and fetuses and highlight macroscopic features which could potentially have significant clinical implications in ophthalmic pathology.

First-Trimester Diagnosis of Supernumerary Hemivertebra.

Hemivertebra is a common cause of congenital scoliosis and results from a lack of formation of one-half of the vertebral body. This condition is very rare and can present as solitary or as a syndrome component: i.e., the split notochord syndrome, which often implies vertebral defects, from a bifid vertebra to hemivertebrae, or fused vertebrae. We describe a case of supernumerary lateral hemivertebra detected prenatally at 12 weeks of gestation and the ultrasonography specifics that lead to early and accurate diagnosis, monitoring during pregnancy, and follow-up at the 4-year period. The case is presented to specify the importance of an early assessment of fetal spine and diagnosis of various conditions, including hemivertebrae, considering the significant association with other anomalies (cardiovascular, urinary, skeletal, gastrointestinal, and central nervous systems), which are most commonly involved. Moreover, the need to counsel future parents on the risks implied by this anomaly is important for the obstetrician. We underline the inclusion of these types of congenital conditions in high-risk pregnancy because of the frequent association with high cesarean delivery rates, growth restriction, delivery before term, and higher morbidity rates.

The Strategy against Iatrogenic Prematurity Due to True Umbilical Knot: From Prenatal Diagnosis Challenges to the Favorable Fetal Outcome.

True umbilical knot (TUK), although not a commonly encountered pathology, hasan important psychological burden on the mother and obstetrician. It has an extremely low prenatal ultrasound diagnosis rate, despite its adverse perinatal outcomes when unknown. We conducted a retrospective observational analytical study on a 7-year period (2015-2021), including all pregnancies overseen by a single fetal-maternal medicine specialist for monitoring and delivery. We analyzed the prenatal detection rate and correlations between prenatal diagnosis of TUK and pregnancy outcome in terms of associated maternal and fetal factors, time and mode of delivery, fetal weight at birth, maternal level of stress, and iatrogenic prematurity. We compared our results with an electronic search of the literature to study the relationship between TUK and prematurity. We prenatally diagnosed 16 TUKs, and there were two false positives and two undiagnosed knots. All of those women had birth at term. The main finding of the review was a small number of studies that included enough cases for analysis. The prematurity rate due to TUK is 14.2%, significantly increased compared to the general population. An umbilical artery flow velocimetry notch in twin pregnancies complicated by TUK was an important ultrasonographic finding. We consider intrauterine fetal death exceptional, and the main adverse neonatal outcome is due to iatrogenic prematurity caused by maternal anxiety of knowing the prenatal diagnosis and mode of delivery. The elective method for diagnosis should be the second-trimester ultrasound scan using three-dimensional (3D) reconstruction and cesarean delivery for a good neonatal outcome. Pregnant women should be counseled to understand the implications of iatrogenic prematurity, especially respiratory distress syndrome, to ensure these infants are delivered at term.

Current Innovative Methods of Fetal pH Monitoring-A Brief Review.

In this study, we explore the "why?", and "how?", monitoring the pH of the fetal scalp is used, and show its limitations. In addition, we review the development of new devices based on the modern physics and nanomaterials serving this topic. Most of the works we found in our search have focused on improving the prognostic of fetal heart rate monitoring, because it is the "golden standard" in determining fetal distress. Although the best-known screening method, it can only provide limited information about the actual status of the fetus. The best predictive assessment, with the highest reproducibility, states that a normal fetal heart rate is indicative of a healthy baby. However, its excellent sensitivity is much reduced when identifying the actual "distress". This is when second-line monitoring methods come into play to guide the diagnostics and direct the obstetrician towards an action plan. Although a historic method, fetal scalp pH sampling is still under review as to its efficiency and place in the current obstetrics. Continuous surveillance of the fetal parameters is important, especially for the fetuses undergoing intrauterine growth restricted (IUGR). Since fetal scalp blood sampling is still under research and is a randomized controlled trial, which compares the relevance of pH and lactates to the obstetrical situation, the maternal-fetal medicine could greatly benefit from the introduction of engineered nanomedicines to the field.

Pregnancy and Delivery in a 27-Year-Old ICD Carrier.

Implantable cardiac devices represent the first line treatment option used not only for secondary prevention of sudden cardiac death but also for primary prevention in patients with cardiac pathologies considered at risk of sudden cardiac death caused by ventricular tachycardia or ventricular fibrillation. The number of women with implantable cardiac devices reaching child bearing age is expected to increase more and more in the next years. Despite this tendency, there are only a few reported cases of pregnancies in implantable cardiac defibrillator carriers, leading to insufficient evidence and clear guideline recommendations on how to manage and monitor pregnancy in patients with this type of cardiac pathology. Closely monitoring within a multidisciplinary team consisting of an obstretician, electrophysiologist and anesthesiologist is required for this group of pregnant patients in order to achieve the best maternal and neonatal results. The present study describes the case of succesful outcome in a 27-year-old implantable cardiac defibrillator carrier implanted after an aborted cardiac arrest and reccurent polymorphic ventricular tachycardia due to myocarditis eight years prior to pregnancy, with an aim to emphasize the monitoring particularities and management during pregnancy.

Implications of human T-lymphotropic virus in pregnancy: A case report and a review of the diagnostic criteria and management proposal.

Human T-lymphotropic virus (HTLV) is considered to be the most highly oncogenic existing virus, being the cause of several fatal diseases such as adult T cell leukemia-lymphoma (ATL) and HTLV-I-associated myelopathy (HAM). The main transmission methods are unprotected sexual intercourse, vertical transmission and breastfeeding and direct exposure to infected blood or tissue. The identification of infected mothers prior to delivery is a highly important step in preventing mother to child transmission. Universal antenatal screening for HTLV is not recommended in Romania, although there are sufficient data demonstrating the risk of vertical transmission. We present the case of an HTLV-1-infected pregnant woman, with an aim to highlight: i) points of strategy for the management of HTLV during pregnancy; ii) the particularities of the course of pregnancy; and iii) the aspects that show the importance of knowing the status regarding the HTLV infection antepartum. The case was particular due to the ascendant proviral load during the pregnancy period, which led to the initiation of antiretroviral therapy and the particular pregnancy outcome with preterm rupture of membranes and fetal growth restriction. According to current recommendations, pregnant women infected with HTLV-1 should be advised to refrain from donating blood, body organs, or other tissues. There is no evidence of the number of individuals infected with this virus in Romania at present, and the diagnosis can only occur by chance. A specific treatment or immunization for HTLV infection does not currently exist, thus preventive methods are the only tool to reduce the prevalence and mortality of this infection.

Prenatal Ultrasound Diagnosis of Double Aortic Arch versus Right Aortic Arch Variant in Vascular Ring Formation - Case Report and Review of the Literature.

Double aortic arch represents a congenital vascular malformation that is characterized by the development of a complete vascular ring around the esophagus and trachea due to an anomaly in the development of branchial arteries. We present the case of a 31-year-old gravida that was referred for fetal ultrasound anomalies screening at 22 weeks and six days of gestation. Routine ultrasound scanning of the fetus revealed a structural aortic arch anomaly consistent with a double aortic arch, with no other cardiac and diextracardiac congenital structural malformations. Knowledge of embryology and imaging spectrum of aortic arch anomalies that are able to form vascular rings around the trachea and esophagus are essential for an accurate antenatal diagnosis and therefore, for a correct clinical management.

Peripheral-type primitive neuroectodermal tumor of the ovary with EWSR1-FLI1 fusion transcript: a case report and brief review of literature.

Primitive neuroectodermal tumors (PNETs) of the ovary are extremely rare tumors composed of undifferentiated small cells with round nuclei and scant cytoplasm. They are rare in general and extremely rare in the female gynecological tract, where they most commonly affect the ovary, followed by the uterine corpus. The most common presenting symptoms are abdominal pain, bloating and the presence of a pelvic mass. Diagnosis mainly relies on immunohistochemical and fluorescence in situ hybridization (FISH). Due to the rarity of these tumors, there are no standard therapeutic guidelines and treatment consists of surgery, various chemotherapy regimens and/or radiotherapy. In this article, we report the case of a 30-year-old female with peripheral-type PNET (pPNET) of the ovary featuring Ewing sarcoma breakpoint region 1-Friend leukemia integration 1 (EWSR1-FLI1) fusion transcript, confirmed by next-generation sequencing (NGS).

Novel Perspectives Regarding CD34 Immunoexpression Patterns in Gangliogliomas.

Gangliogliomas are extremely rare central nervous tumors composed of an admixture of glial and neuroepithelial elements. Gangliogliomas mainly affect the temporal lobe and occur in the pediatric population. There are several controversies in the scientific literature regarding these tumors, which debuted with the exclusion of grade II gangliogliomas in the 2006 edition of the current World Health Organization (WHO) classification. The upcoming edition due in the last months of 2021 is not expected to include changes regarding the current classification of glio-neuronal tumors. This vision has led to a number of articles that have pushed for the reintroduction of this category. However, these articles support the reintroduction of this degree in terms of prognosis and evolution, without providing clear criteria for the inclusion of certain gangliogliomas in this category. On the other hand, there are uncertainties about the relationship of gangliogliomas with focal cortical dysplasia. The coexistence of the two entities, as well as their succession are occasionally encountered in practice and have led to numerous studies that have tried to clarify the relationship between them. The most common and most accessible element in routine practice is the immunoreactivity for CD34. Both entities express this marker, and dual lesions express the highest percentage of immunoreactivity for CD34. In this article, we study the expression of CD34 on a series of cases including both grade I gangliogliomas and anaplastic gangliogliomas diagnosed between 2011 and 2020 in a Neuropathology Unit in Bucharest Romania.

A Comprehensive Study Regarding the Intrauterine Development of Nails.

The nail apparatus serves as a protective layer over the dorsal aspect of each distal phalanx of both hands and feet. Besides protection, other functions include serving as part of defense or attack mechanisms, scratching, and dexterity. Nail development has been a subject of interest since the 19th century, from both the phylogenetic and ontogenetic points of view. Despite the early spark of interest, nail embryology has yet been analyzed by a relatively small number of scientists. In the Department of Anatomy of "Carol Davila" University of Medicine and Pharmacy, we performed a morphological analysis on 41 embryos and fetuses with gestational ages that varied between 6 and 29 weeks.

Breast cancer mortality gaps in Romanian women compared to the EU after 10 years of accession: Is breast cancer screening a priority for action in Romania? (Review of the Statistics).

Breast cancer remains the most common cause of morbidity and mortality by cancer in females worldwide, even though it is largely preventable through population screening. Despite notable progress in the last years in the EU, breast cancer screening programs still maintain wide variations among countries and socio-economic groups. This statistical review aimed to investigate the breast cancer-related health gaps in Romanian women compared to the average EU female population after 10 years of accession (2007-2016). We evaluated breast cancer-related deaths, age-standardized mortality rates and contribution of breast cancer to life expectancy. Trends and percentage changes were compared between Romania and EU-27 for breast cancer, all cancer and all causes of mortality. We found a higher increase of breast cancer deaths in Romania, an increasing trend of mortality (opposite to EU) and a contribution to life expectancy at birth that increased gradually from 0.45 to 0 48 years. All these health gaps compared to EU are aggravated by the fact that no population screening for breast cancer is organized in the country. The opportunities for organizing such a program are consistent, but they should be increased in the future, in order to control the health gap between Romania and EU.