Endometriosis and the Role of Pro-Inflammatory and Anti-Inflammatory Cytokines in Pathophysiology: A Narrative Review of the Literature.

Endometriosis is a chronic inflammatory disease, which explains the pain that such patients report. Currently, we are faced with ineffective, non-invasive diagnostic methods and treatments that come with multiple side effects and high recurrence rates for both the disease and pain. These are the reasons why we are exploring the possibility of the involvement of pro-inflammatory and anti-inflammatory molecules in the process of the appearance of endometriosis. Cytokines play an important role in the progression of endometriosis, influencing cell proliferation and differentiation. Pro-inflammatory molecules are found in intrafollicular fluid. They have an impact on the number of mature and optimal-quality oocytes. Endometriosis affects fertility, and the involvement of endometriosis in embryo transfer during in vitro fertilization (IVF) is being investigated in several studies. Furthermore, the reciprocal influence between anti-inflammatory and pro-inflammatory cytokines and their role in the pathogenesis of endometriosis has been assessed. Today, we can affirm that pro-inflammatory and anti-inflammatory cytokines play roles in survival, growth, differentiation, invasion, angiogenesis, and immune escape, which provides a perspective for approaching future clinical implications and can be used as biomarkers or therapy.

GATA4 rs61277615, rs73203482, and rs35813172 in Newborns with Transposition of the Great Arteries.

Congenital heart disease is the most common malformative pathology in newborns, with a worldwide incidence at 0.4-5%. We investigated the possible relationship between variations in nucleotide sequences and specific cardiac malformations in the GATA-binding factor 4 (GATA4) exon 1 region by using Sanger sequencing. Forty-four newborns from a third-level neonatal intensive care unit who were diagnosed with nonsyndromic, ductal-dependent congenital heart disease (i.e., transposition of the great arteries or ductal-dependent coarctation of the aorta) were enrolled. Their DNA was extracted using commercial methods and tested using the multiplex ligation-dependent probe amplification (MLPA) technique. The Sanger sequencing for GATA4 exon 1 in the newborns' DNA identified rs61277615, rs73203482, and rs35813172 variants not reported in the ClinVar archive of human variations in newborns previously diagnosed with transposition of the great arteries (n=5) and coarctation of the aorta (n=1). The identification of these novel variants in newborns with transposition of the great arteries or ductal-dependent coarctation of the aorta may be the first step in determining the variants' contribution to the occurrence of congenital heart disease. However, these results may be inconclusive, since the observed variants within GATA4 gene were not previously reported.

Diagnosis and Management of Dysgerminomas with a Brief Summary of Primitive Germ Cell Tumors.

Dysgerminoma represents a rare malignant tumor composed of germ cells, originally from the embryonic gonads. Regarding its incidence, we do not have precise data due to its rarity. Dysgerminoma occurs at a fertile age. The preferred treatment is the surgical removal of the tumor succeeded by the preservation of fertility. Even if a multidisciplinary team, founded in 2009 by a gynecologist, an oncologist, a pediatric oncologist and a pediatric surgeon, under the guidance of the Malignant Germ Cell International Consortium (MaGIC), studies this type of tumor, issues still remain related to the lack of a randomized study and to both the management and understanding of the concept of OMGCTs (ovarian malignant germ cell tumors). The aim of this review is to present from the literature the various approaches for this type of tumor, and, regarding innovative therapies or possible prevention, which can be applied in clinical practice. Multidisciplinarity and treatment in reference centers have proven their usefulness as well.

Oxidative-Stress Related Gene Polymorphism in Endometriosis-Associated Infertility.

Background and Objectives: Endometriosis is a benign inflammatory disease associated with infertility and chronic pelvic pain, estimated to affect 7−10% of reproductive-age women, with the possibility of malignant transformation. Recent studies focus on oxidative stress and genetic mutations as risk factors in the pathophysiology of endometriosis-associated infertility. Materials and Methods: This case-control study is the first in Eastern European women that aimed to investigate four genes' genetic polymorphisms that encode antioxidant enzymes involved in oxidative stress (glutathione peroxidase 1, GPX1 198Pro > Leu, catalase CAT-262C > T, glutathione S-transferase M1, and T1 null genotype) and their association with endometriosis-related infertility. We compared 103 patients with endometriosis-associated infertility with 102 post-partum women as the control group. Results: The endometriosis group had a mean age of 34.5 +/− 6.12 years, while the control group's mean age was 35.03 +/− 5.95 years. For CAT-262C > T polymorphism, the variant genotypes were significantly more frequent in the endometriosis group. Moreover, for the GPX1 198Pro > Leu, the endometriosis group had significantly more frequent CT and TT genotypes. The null genotype of GSTM1 was detected significantly higher in the endometriosis group. No significant differences were found in the frequency of GSTT1 between the two groups. This study suggests that GPX1 198Pro > Leu, CAT-262C > T, and GSTM1 polymorphisms may be risk factors and that the association between the GSTM1-GSTT1 null genotype may play a significant role in endometriosis-associated infertility. Moreover, this study suggests that the GSTT1 null genotype does not influence the disease. Visual identification of endometriotic lesions with microscopic confirmation is the accepted gold standard for diagnosing endometriosis, but general anesthesia and laparoscopy are required. Conclusions: In this regard, a panel of genetic or laboratory markers is needed for the early diagnostics of this prevalent disease, especially in the case of young patients with future pregnancy intention.

A Race against the Clock: A Case Report and Literature Review Concerning the Importance of ADAMTS13 Testing in Diagnosis and Management of Thrombotic Thrombocytopenic Purpura during Pregnancy.

Thrombocytopenic purpura (TTP) is a rare, potentially fatal pathology characterized by microangiopathic thrombotic syndrome and caused by an acute protease deficiency of von Willebrand factor, ADAMTS13. Moreover, ADAMTS13 deficiency promotes microthrombosis led by the persistence of ultra-large VWF multimers in the blood circulation. According to the few studies involving pregnant participants, the heterogeneity of manifestations has made this pathology difficult to diagnose, with an unexpected occurrence and increased risk of maternal and fetal morbidity and mortality. We reported on the case of a 28-year-old pregnant woman with an obstetric score of G2P0 who presented to the obstetrics and gynecology department of our clinic with the complaint of minimal vaginal bleeding. The evolution of our case was severe and life-threatening, a "race against the clock", with our goal being to emphasize the importance and difficulty of diagnosing TTP in the absence of specific symptomatology. We faced a lack of technological support for a correct and complete diagnosis, and the first manifestation of this disease was the intrauterine death of the fetus. After completing all the necessary procedures, the placental tissue was sent for further histopathological evaluation. We highlighted the importance of monitoring ADAMTS13 for relapses monthly, with prophylaxis being essential for maternal and fetal mortality and morbidity.

Transvaginal Ultrasound Combined with Strain-Ratio Elastography for the Concomitant Diagnosis of Uterine Fibroids and Adenomyosis: A Pilot Study.

Uterine fibroids (UFs) and adenomyosis (AM) represent two benign uterine conditions that can affect fertility and are most frequently commonly responsible for abnormal uterine bleeding and chronic pelvic pain. Their differential diagnosis still represents a challenge, and several authors advise the addition of elastography to transvaginal ultrasound (TVUS) for a more accurate imagistic recognition. Through this study, we aimed to assess the diagnostic accuracy of TVUS combined with strain-ratio elastography (SRE) in concomitant AM and UFs. We conducted a study on 17 patients diagnosed with concomitant UFs and AM undergoing hysterectomy and 46 healthy patients. TVUS combined with SRE was conducted in each patient, focusing on identifying rigidity patterns of the lesions. Significantly higher mean SR and maximum SR values were identified among both AM and UF lesions as opposed to controls (p < 0.01), with the highest tissue stiffness being encountered among AM lesions, which allows for the differentiation of UF (p < 0.01) and concomitant identification of both lesions. These results are reflected by higher cut-off values obtained for AM, both for mean SR (5.42 vs. 2.85) and maximum SR (5.80 vs. 3.30). TVUS combined with SRE showed good diagnostic performance in identifying coexisting UFs and AM within the same uterine specimen. Future studies on wider populations are required to validate our findings.

Atypical Polypoid Adenomyoma of the Vagina: Follow Up and Subsequent Evolution: A Case Report and Update.

Atypical polypoid adenomyoma (APA) is a rare tumor developed from a mix of cells of epithelial and mesenchymal origin. We present the case of an 84-year-old patient with atypical polypoid adenomyoma on the vaginal vault, after total hysterectomy with total adnexectomy for endometrial hyperplasia with atypia four years ago. Not following regular indicated gynecological appointments, the symptoms presented were vaginal bleeding and anemia. The importance of the case consists both in the unique way in which the adenomyoma appears on the vaginal vault and in the subsequent evolution of this pathology. After complete resection, it recurs in five months with a malignant transformation into carcinosarcoma. This fact shows that adenomas can turn not only into carcinomas but also the mesenchymal component can progress to sarcoma, a fact of exceptional rarity. Follow-up and accurate diagnosis are essential for proper management, which is a challenge anyway due to the lack of case studies.

Value of Strain-Ratio Elastography in the Diagnosis and Differentiation of Uterine Fibroids and Adenomyosis.

Benign uterine disorders, including uterine fibroids (UF) and adenomyosis (AM), can impact the life quality and fertility of women of reproductive age. Transvaginal ultrasound (TVUS) has long been used for their early identification, but its combined use with elastography seems to improve diagnostic accuracy of UF and AM. Thus, a prospective pilot study was conducted on 79 patients who underwent hysterectomy (25 microscopically diagnosed with AM and 53 with UF), with the aim of assessing the ability of TVUS combined with strain ratio elastography (SE) to accurately diagnose and distinguish UF and AM. Significantly higher mean and maximal strain ratio (SR) values were identified for patients with histologically confirmed AM as opposed to those with UF (p < 0.001). Diagnostic sensitivity and specificity, calculated in comparison with histology results, were higher for UF than AM. Receiver operating characteristic (ROC) analysis was applied between the two study groups, revealing cutoff values of 7.71 for mean SR and 8.91 for maximal SR, respectively, with good sensitivity and specificity parameters (100% and 96.23%; 96% and 96.23%). Our results support the use of TVUS in combination with SE for the positive and differential diagnosis of UF and AM, through identification of their particular tissue stiffness features.

A multicenter cross-sectional study of episiotomy practice in Romania.

RATIONALE, AIMS, AND OBJECTIVES: The aim of this study was to focus attention on episiotomy practice in Romanian maternity units in order to identify factors associated with the very high rate of the procedure in Romania and to consider strategies to reduce it. METHODS: In this clustered cross-sectional study, a total of 11 863 patients were recorded in eight Romanian maternity units to assess the prevalence of episiotomy. A random effects Poisson model was used to estimate the prevalence rate in univariate and multivariate models. RESULTS: Among the 11 863 patients included for analysis, 8475 (71.4%) had an episiotomy. The prevalence of episiotomy was 92.7% for the first vaginal birth, 73.2% for the second vaginal birth, and 35% for the third vaginal birth. The overall rate of suturing was higher than the episiotomy rate for all patients (total rate 79.2%). The likelihood of exiting the maternity ward with an intact perineum after the first vaginal birth was less than 5% at the first vaginal birth. CONCLUSIONS: In conclusion, routine episiotomy is the norm in Romanian maternity units, with episiotomy rates among the highest in Europe. Episiotomy use is mainly driven by local professional norms, experiences, previous training, and practitioners' decisions rather than evidence, guidelines, or variations in patient needs at the time of vaginal birth.

Neutrophil Gelatinase-Associated Lipocalin as a Marker for Renal Dysfunction Detection in Critically Ill Patients with Increased Intraabdominal Pressure.

INTRODUCTION: Elevated intraabdominal pressure (IAP) it is known to have an impact on renal function trough the pressure transmitted from the abdominal cavity to the vasculature responsible for the renal blood flow. Intraabdominal pressure is found to be frequent in intensive care patients and also to be a predictor of mortality. Intra-abdominal high pressure is an entity that can have serious impact on intensive care admitted patients, studies concluding that if this condition progresses to abdominal compartment syndrome mortality is as high as 80%. AIM: The aim of this study was to observe if a link between increased intraabdominal pressure and modification in renal function exists (NGAL, creatinine clearance). MATERIAL AND METHOD: The study enrolled 30 critically ill patients admitted in the Intensive Care Unit of SCJU TîrguMures between November 2015 and August 2016. The study enrolled adult, hemodynamically stable patients admitted in intensive critical care - defined by a normal blood pressure maintained without any vasopressor or inotropic support, invasive monitoring using PICCO device and abdominal pressure monitoring. RESULTS: The patients were divided into two groups based on the intraabdominal pressure values: normal intraabdominal pressure group= 52 values and increased intraabdominal group= 35 values. We compared the groups in the light of NGAL values, 24 hours diuresis, GFR and creatinine clearance. The groups are significantly different when compared in the light of NGAL values and GFR values. We obtained a statistically significant correlation between NGAL value and 24 hour diuresis. No other significant correlations were encountered between the studied items. CONCLUSIONS: NGAL values are increased in patients with high intraabdominal pressure which may suggest its utility as a cut off marker for patients with increased intraabdominal pressure. There is a significant decreased GFR in patient with elevated intraabdominal pressure, observation which can help in early detection of renal injury in patients due to high intraabdominal pressure. No correlation was found between creatinine clearance and increased intraabdominal pressure.