Determination of biomarker candidates for the placenta accreta spectrum by plasma proteomic analysis.

Placenta accreta spectrum (PAS) presents a significant obstetric challenge, associated with considerable maternal and fetal-neonatal morbidity and mortality. Nevertheless, it is imperative to acknowledge that a noteworthy subset of PAS cases remains undetected until the time of delivery, thereby contributing to an augmented incidence of morbidity among the affected individuals. The delayed identification of PAS not only hinders timely intervention but also exacerbates the associated health risks for both the maternal and fetal outcomes. This underscores the urgency to innovate strategies for early PAS diagnosis. In this study, we aimed to explore plasma proteins as potential diagnostic biomarkers for PAS. Integrated transcriptome and proteomic analyses were conducted to establish a novel diagnostic approach. A cohort of 15 pregnant women diagnosed with PAS and delivering at Inonu University Faculty of Medicine between 01/04/2021 and 01/01/2023, along with a matched control group of 15 pregnant women without PAS complications, were enrolled. Plasma protein identification utilized enzymatic digestion and liquid chromatography-tandem mass spectrometry techniques. Proteomic analysis identified 228 plasma proteins, of which 85 showed significant differences (P < 0.001) between PAS and control cases. We refined this to a set of 20 proteins for model construction, resulting in a highly accurate classification model (96.9% accuracy). Notable associations were observed for proteins encoded by P01859 (Immunoglobulin heavy constant gamma 2), P02538 (Keratin type II cytoskeletal 6A), P29622 [Kallistatin (also known as Serpin A4)], P17900 (Ganglioside GM2 activator Calmodulin-like protein 5), and P01619 (Immunoglobulin kappa variable 3-20), with fold changes indicating their relevance in distinguishing PAS from control groups. In conclusion, our study has identified novel plasma proteins that could serve as potential biomarkers for early diagnosis of PAS in pregnant women. Further research and validation in larger PAS cohorts are necessary to determine the clinical utility and reliability of these proteomic biomarkers for diagnosing PAS.

Assessing lipoxin-mediated inflammatory responses in the second trimester of pregnancy among women with obesity: A comprehensive analysis.

Objective: This study aimed to explore the relationship between maternal plasma lipoxin A4 (LXA4) levels during the second trimester of pregnancy and certain proinflammatory molecules, such as interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α), as well as the antiangiogenic factor vascular endothelial growth factor receptor 1 (VEGFR-1), in conjunction with obesity among pregnant women. Materials and Methods: A total of 30 pregnant women with obesity were compared with 30 pregnant women of normal weight, matched for both age and gestational week. Plasma samples were collected from all participants between the 18th and 28th weeks of pregnancy. The levels of LXA4, VEGFR-1, IL-6, and TNF-α were quantified using enzyme-linked immunosorbent assay. Results: Plasma levels of LXA4 were notably lower in pregnant women with obesity, whereas levels of TNF-α and VEGFR1 were significantly higher (p=0.041, p<0.001, and p<0.001, respectively). There was no significant difference in IL-6 levels between groups (p=0.072). The binary logistic regression model revealed significant associations between obesity and the examined inflammatory mediators. Specifically, the results demonstrated that higher levels of LXA4 were linked to a reduced obesity risk, with each unit increase corresponding to a 0.926-fold decrease in the likelihood of obesity. Conversely, elevated levels of TNF-α and VEGFR1 were associated with an increased risk of obesity. Conclusion: The study concluded that increased body mass index during pregnancy affects the levels of plasma lipoxin, cytokines, and angiogenesis-related factors. Although the exact mechanisms remain unclear, the observed changes suggest a disruption in the metabolic systems of women with obesity, which may influence physiological changes during pregnancy and lead to obesity-related pathological conditions.

Amnioinfusion vs. standard management for the second trimester PPROM: a systematic review and meta-analysis of observational studies and RCTs.

OBJECTIVE: This meta-analysis aims to review the effect of serial transabdominal amnioinfusion (TAI) on short-term and long-term perinatal outcomes in mid-trimester preterm premature rupture of membranes (PPROM). METHODS: Literature searches of PubMed, Web of Sciences, Scopus, and Cochrane Library were performed from their inception to April 2022. Studies comparing conventional treatment with serial TAI in women with proven PPROM at less than 26 + 0 weeks of gestation with oligohydramnios were included. Studies that included oligohydramnios due to other reasons such as fetal growth retardation or renal anomalies were excluded. Risk of bias in observational studies was assessed using the tool of the Cochrane Review group identified as risk of bias in non-randomized studies - of interventions. The risk of bias assessments for RCTs were performed according to the Cochrane risk-of-bias tool for randomized trials. An I2 score was used to assess the heterogeneity of included studies. The analyses were performed by using random-effect model, and the results were expressed as relative risk (RR) or mean difference with 95% confidence intervals (CIs). RESULTS: Overall, eight relevant studies including five observational studies (n = 252; 130 women allocated to the intervention) and three RCTs (n = 183; 93 women allocated to the intervention) were eligible. The pooled latency period was 21.9 days (95% CI, 13.1-30.8) and 5.8 days (95% CI, -11.6-23.2) longer in the TAI group in the observational studies and RCTs, respectively. The perinatal mortality rate reduced in the intervention group when tested in observational studies (RR 0.68; 95% CI, 0.51-0.92), but not in RCTs (RR 0.79; 95% CI, 0.56-1.13). The rate of long-term healthy survival was higher in the children whose mothers were treated with the TAI (35.7%) than those were treated with the standard management (28.6%) (RR 1.30, 95% CI 0.47-3.60, "best case scenario"). CONCLUSIONS: The efficacy of serial TA on early PPROM associated morbidity and mortality is not attested. Additional randomized control trials with adequate power are needed.

The role of different Doppler parameters in predicting adverse neonatal outcomes in fetuses with late-onset fetal growth restriction.

Objective: The aim of this study is to clarify the role of different Doppler parameters such as umbilicocerebral ratio (UCR), cerebroplacentouterine ratio (CPUR), aortic isthmus, renal artery, and umbilical vein flow Doppler in predicting adverse neonatal outcomes in fetuses with late -onset fetal growth restriction. Materials and Methods: The study included all patients diagnosed with fetal growth restriction at 32-39 weeks' gestation between 01/02/2020 and 01/02/2022 and treated at the Department of Obstetrics and Gynecology, Inonu University School of Medicine. Results: Patients included in the study had a median gestational week at delivery of 37 (minimum 33+0-maximum 39+0), median CPR of 1.42 (minimum-maximum 0.43-3.57), and median UCR of 0.7 (minimum-maximum 0.28-2.3). Receiver operating characteristic analysis was performed to determine the performance of the measured obstetric Doppler parameters in predicting the development of adverse neonatal outcomes. Umbilical venous blood flow showed the best performance in predicting adverse neonatal outcomes [area under the curve 0.952, 95% confidence interval (CI) 0.902-0.981, p<0.001]. Multivariate logistic regression analysis showed that fetuses with abnormal CPUR had a 4.5-fold (95% CI 0.084-0.583, p=0.02) increased risk of adverse neonatal outcome, whereas fetuses with abnormal umbilical venous flow had a 1.07-fold (95% CI 0.903-0.968, p<0.001) increased risk of adverse neonatal outcome. Conclusion: The results of this study demonstrate that the use of UCR, CPUR, umbilical venous flow, and aortic isthmus PI Doppler parameters along with umbilical artery PI and CPR are effective in predicting adverse neonatal outcomes in fetuses with late -onset fetal growth restriction.

Endometrial Cancer Individualized Scoring System (ECISS): A machine learning-based prediction model of endometrial cancer prognosis.

OBJECTIVE: To establish a prognostic model for endometrial cancer (EC) that individualizes a risk and management plan per patient and disease characteristics. METHODS: A multicenter retrospective study conducted in nine European gynecologic cancer centers. Women with confirmed EC between January 2008 to December 2015 were included. Demographics, disease characteristics, management, and follow-up information were collected. Cancer-specific survival (CSS) and disease-free survival (DFS) at 3 and 5 years comprise the primary outcomes of the study. Machine learning algorithms were applied to patient and disease characteristics. Model I: pretreatment model. Calculated probability was added to management variables (model II: treatment model), and the second calculated probability was added to perioperative and postoperative variables (model III). RESULTS: Of 1150 women, 1144 were eligible for 3-year survival analysis and 860 for 5-year survival analysis. Model I, II, and III accuracies of prediction of 5-year CSS were 84.88%/85.47% (in train and test sets), 85.47%/84.88%, and 87.35%/86.05%, respectively. Model I predicted 3-year CSS at an accuracy of 91.34%/87.02%. Accuracies of models I, II, and III in predicting 5-year DFS were 74.63%/76.72%, 77.03%/76.72%, and 80.61%/77.78%, respectively. CONCLUSION: The Endometrial Cancer Individualized Scoring System (ECISS) is a novel machine learning tool assessing patient-specific survival probability with high accuracy.

Evaluation of serum neopterin, periostin, Tenascin-C, tissue inhibitor of metalloproteinase-1 and matrix metalloproteinase-2 levels in obese pregnant women

Objective: To investigate the role of extracellular matrix proteins in the molecular mechanism of inflammatory response in obese pregnant women by comparing serum levels of neopterin, periostin, Tenascin-C, tissue inhibitor of metalloproteinase-1, and matrix metalloproteinase-2 between obese and normal weight pregnant women in the third trimester. Materials and Methods: A prospective cross-sectional study was conducted between April 2021 and December 2021. A total of 84 pregnant women were included and three groups were formed with 28 participants in each group. Results: Serum levels of neopterin, periostin, Tenascin-C and tissue inhibitor of metalloproteinase-1 were significantly higher in class II-III obese pregnant women than in class I obese and normal-weight women (p=0.002, p<0.001, p<0.001, and p<0.001, respectively). There was no significant difference in serum matrix metalloproteinase-2 levels between the groups (p=0.769). Receiver operating characteristic curve analysis showed that Tenascin-C and periostin were effective in predicting pre-eclampsia [area under the curve (AUC)=0.82, 95% confidence interval (CI), 0.72-0.90, p<0.001 and AUC=0.71, 95% CI, 0.60-0.80, p=0.007, respectively]. Conclusion: This study demonstrated that class II-III obese pregnant women had significantly higher serum levels of neopterin, periostin, Tenascin-C, and tissue inhibitor of metalloproteinase-1 in the third trimester. These higher serum levels may be associated with the adverse perinatal effects of obesity during pregnancy.

The predictive value of maternal serum AFP to PAPP-A or b-hCG ratios in spontaneous preterm birth.

The use of the second trimester alpha-fetoprotein (AFP) along with the first trimester pregnancy-associated plasma protein-A (PAPP-A) has been found to be useful in the estimation of unfavourable pregnancy outcome. Our aim in this study was to determine the relationship between maternal PAPP-A and b-hCG and AFP concentrations in spontaneous preterm birth (sPTB). This prospective cohort study included 372 singleton pregnancies with PAPP-A, b-hCG and AFP levels in the first trimester, which were converted to multiples of the median (MoM). The predictive ability of AFP-to-PAPP-A and AFP-to-b-hCG ratios for sPTB was evaluated. The risk for sPTB ≤34 weeks increased in women with AFP-to-PAPP-A ratio >7 (OR 2.9, 95% CI 1.2-6.4). Women with AFP-to-b-hCG ratio >0.6 had a 3.5-fold higher risk for sPTB ≤32 weeks. Increased maternal AFP-to-PAPP-A or AFP-to-b-hCG ratios in the first trimester may help to predict pregnant women at high risk for sPTB, and this may be beneficial in developing management plans.Impact StatementWhat is already known on this subject? There is a synergistic association between the combination of low pregnancy-associated plasma protein-A (PAPP-A) in the first trimester with alpha-fetoprotein (AFP) in the second trimester with subsequent development of PTB. Maternal serum biochemical markers measured as a part of aneuploidy screening are reflective of pregnancy adverse outcomes related with placental insufficiency. PAPP-A and AFP have a low predictive ability to determine women at high risk for preterm birth.What do the results of this study add? Elevated AFP:PAPP-A or AFP:B-HCG ratio in the first trimester is associated with increased risk for sPTB. The ratios of these biochemical markers in the first trimester may be beneficial to identify women at high risk for sPTB.What are the implications of these findings for clinical practice and/or further research? The ratios may predict pregnant women at high risk for sPTB, and such risk may be helpful in the development of a management plan. Incorporation of AFP:PAPP-A or AFP:B-HCG ratios in the first trimester may help to improve the screening efficacies, and provide a simple alternative tool.

Analysis of prognostic factors in Grade 3 endometrioid type endometrial carcinoma.

OBJECTIVE: To investigate the prognostic factors of patients with Grade 3 endometrioid endometrial cancer (G3EEC). METHODS: This four-center, retrospective study included a total of 129 women with G3EEC. Demographic, clinicopathologic, and survival data were collected. Kaplan-Meier method was used for survival analysis. Predictors of outcome were analyzed using Cox proportional hazards models. RESULTS: Median age at the time of diagnosis was 63 (range 39-87) years and median follow up was 37 (range 6-126) months. For the entire cohort, the 5-year disease-free survival (DFS) and overall survival (OS) were 54.3% and 63.6%, respectively. The 5-year DFS rates for lymphovascular space invasion (LVSI) -positive and -negative patients were 41.6% and 88.3%, respectively (P < 0.001). The 5-year OS rates for LVSI-positive and -negative patients were 54.7% and 88.3%, respectively (P = 0.001). Positive LVSI status was identified as the independent prognostic factor for decreased DFS and OS (hazard ratio [HR] 5.5, 95% confidence interval [CI] 1.65-18.86; P = 0.006 versus HR 4.4, 95% CI 1.33-14.58; P = 0.013, respectively). CONCLUSION: LVSI seems to be an independent prognostic factor for decreased DFS and OS in G3EEC patients.

Perinatal and neonatal outcomes of women with very early preterm premature rupture of membranes treated via serial transabdominal amnioinfusion and expectant management: Experience of a tertiary referral center in Turkey.

AIM: We compared the outcomes of serial transabdominal amnioinfusion and expectant management on the perinatal and neonatal outcomes of pregnancies complicated with very early preterm premature rupture of membranes (PPROM). METHODS: We retrospectively reviewed the records of patients with very early PPROM admitted to the University of Inonu School of Medicine from 2014 to 2019. All such patients received comprehensive counseling on the possible prognoses; all were offered pregnancy termination, expectant management, and serial transabdominal infusion. RESULTS: Sixty-three women met the inclusion criteria; 36 were assigned to the expectant management group and 27 were assigned to the amnioinfusion group. The median delivery latency and the gestational age at delivery were significantly higher in the amnioinfusion than the expectant management group [35 (11-90), 14 (7-48), p < 0.001; 27.6 (22.1-34.0), 22.3 (19.0-26.5), p < 0.001, respectively]. Serial transabdominal amnioinfusion was associated with significantly less neonatal mortality than expectant management (29.6 vs 83.3%, p < 0.001). Multivariate binary logistic regression showed that the odds of neonatal mortality were 6.12 times higher among neonates in the expectant management group compared to that of the serial transabdominal amnioinfusion group after adjusting for potential confounders. Severe neonatal morbidities were significantly more common in the expectant management group than in the amnioinfusion group (p = 0.011). CONCLUSION: The present study has demonstrated a significant positive effect of serial transabdominal amnioinfusion procedure on latency period and neonatal morbidity and mortality in pregnant women complicated with very early PPROM.

Evaluation of dyslipidemia in preeclamptic pregnant women and determination of the predictive value of the hemato-lipid profile: A prospective, cross-sectional, case-control study.

Objective: In this study, we examined the serum hematologic and lipid parameters of pregnant women with preeclampsia and an age- and gestational-age matched normotensive control group. We also compared the ratios of hemato-lipid parameters defined as systemic inflammatory markers and determined the predictive value of these values in preeclampsia. Materials and Methods: All patients diagnosed with late-onset preeclampsia or severe preeclampsia between 34 and 40 weeks of gestation at Inonu University Faculty of Medicine between March 2019 and October 2020 were included. Results: A total of 253 pregnant women were included in the study period. When the study groups were compared in terms of hematological and blood lipid profile; while serum lymphocyte, triglyceride, and total cholesterol levels were significantly higher in the preeclampsia group than in the control group (p<0.001, p<0.001, p=0.013, respectively); high-density lipoprotein (HDL)-cholesterol levels were found to be significantly lower (p=0.017). The cut-off value for the monocyte/HDL ratio in predicting severe preeclampsia was 16.65 with 59.0% sensitivity and 85.4% specificity [the area under the receiver operating characteristic 0.756, 95% confidence interval (CI) 0.681-0.821, p<0.001]. Multivariate analysis showed that the monocyte/HDL ratio was independently associated with both preeclampsia and severe preeclampsia [odds ratio (OR): 1.094; 95% CI 1.009-1.185 and OR: 1.731; 95% CI 1.218-2.459, respectively]. Conclusion: This study demonstrated that serum triglyceride and total cholesterol levels were significantly higher and serum HDL-cholesterol levels were significantly lower in pregnant women with late-onset preeclampsia compared to normotensive pregnant women. Additionally, this study revealed that the measurement of monocyte/HDL ratio in the pregnant population could be a useful clinical tool for predicting preeclampsia.

Prenatal diagnosis of a rare isolated thoracic-type ectopia cordis with complete form: a case report.

Ectopia cordis (EC) is a rare malformation that occurs as an isolated lesion or as part of the pentalogy of Cantrell which is characterized by midline closure defects. This was first described by Haller et al. in 1706. EC is seen with a frequency of 5.5-7.9 per 1 million births. It has five types that are: cervical, cervico-thoracic, thoracic, thoraco-abdominal, and abdominal. Its differentiation from the pentalogy of Cantrell, first described by Cantrell in 1958, must be done well. Thoracic type has the worst prognosis and due to this poor prognosis in the postnatal period, termination may be offered to these patients as an option. In this paper, a case of an isolated thoracic-type complete EC detected in the prenatal ultrasonography of a pregnant woman referred to our clinic at the 18 weeks and 3 days of gestation is presented.

Placenta accreta risk-antepartum score in predicting clinical outcomes of placenta accreta spectrum: A multicenter validation study.

OBJECTIVE: To validate the use of placenta accreta risk-antepartum (PAR-A) score as a predictive tool of clinical outcomes of placenta accreta spectrum (PAS). METHODS: This is a prospective study, conducted in six PAS specialized centers in six different countries. The study was conducted between October 1, 2020 and March 31, 2021. Women who were provisionally diagnosed with PAS during pregnancy were considered eligible. A machine-learning-based PAR-A score was calculated. Diagnostic performance of the PAR-A score was evaluated using a receiver operating characteristic curve, for perioperative massive blood loss and admission to intensive care unit (ClinicalTrials.gov identifier NCT04525001). RESULTS: Of 97 eligible women, 86 were included. PAS-associated massive blood loss occurred in 10 patients (11.63%). Median PAR-A scores of massive blood loss in the current cohort were 8.9 (interquartile range 6.9-14.1). In predicting massive blood loss, the area under the curve of PAR-A scores was 0.85 (95% confidence interval [CI] 0.74-0.95), which was not significantly different from the original cohort (P = 0.2). PAR-A score prediction of intensive care unit admission was slightly higher compared with the original cohort (0.88, 95% CI 0.81-0.95; P = 0.06). CONCLUSION: PAR-A score is a novel scoring system of PAS outcomes, which showed external validity based on current data.

Prediction of clinical outcomes in women with placenta accreta spectrum using machine learning models: an international multicenter study.

INTRODUCTION: Placenta accreta spectrum is a major obstetric disorder that is associated with significant morbidity and mortality. The objective of this study is to establish a prediction model of clinical outcomes in these women. MATERIALS AND METHODS: PAS-ID is an international multicenter study that comprises 11 centers from 9 countries. Women who were diagnosed with PAS and were managed in the recruiting centers between 1 January 2010 and 31 December 2019 were included. Data were reanalyzed using machine learning (ML) models, and 2 models were created to predict outcomes using antepartum and perioperative features. ML model was conducted using python® programing language. The primary outcome was massive PAS-associated perioperative blood loss (intraoperative blood loss ≥2500 ml, triggering massive transfusion protocol, or complicated by disseminated intravascular coagulopathy). Other outcomes include prolonged hospitalization >7 days and admission to the intensive care unit (ICU). RESULTS: 727 women with PAS were included. The area under curve (AUC) for ML antepartum prediction model was 0.84, 0.81, and 0.82 for massive blood loss, prolonged hospitalization, and admission to ICU, respectively. Significant contributors to this model were parity, placental site, method of diagnosis, and antepartum hemoglobin. Combining baseline and perioperative variables, the ML model performed at 0.86, 0.90, and 0.86 for study outcomes, respectively. Ethnicity, pelvic invasion, and uterine incision were the most predictive factors in this model. DISCUSSION: ML models can be used to calculate the individualized risk of morbidity in women with PAS. Model-based risk assessment facilitates a priori delineation of management.

Comparison of preoperative serum neopterin, periostin, indoleamine 2,3-dioxygenase, YKL-40, and tenascin-C levels with current tumor markers for early-stage endometrial cancer.

OBJECTIVE: To compare the predictive value of serum levels of neopterin, periostin, YKL-40, tenascin-C (TNC), and indoleamine 2,3-dioxygenase (IDO) with current tumor markers for the primary diagnosis of early-stage endometrial cancer. METHODS: A prospective cross-sectional study was conducted between January 2020 and November 2020. A total of 59 patients (38 women newly diagnosed with early-stage endometrial cancer [study group] and 21 women with benign endometrial pathologies [control group]) were enrolled. Blood samples were collected prior to surgery and underwent immunoassay analysis. RESULTS: Carcinoembryonic antigen (CEA), periostin, and IDO levels were significantly higher in the study group than the control group (P = 0.008, P = 0.034, and P = 0.003, respectively). Receiver operating characteristic curve analysis revealed that IDO, periostin, and CEA were good predictors of early-stage endometrial cancer (AUC = 0.733, 95% CI, 0.602-0.840, P < 0.002; AUC = 0.668, 95% CI, 0.533-0.785, P = 0.018; and AUC = 0.709, 95% CI, 0.576-0.820, P = 0.002, respectively). Correlation analysis revealed no significant correlation of any biomarker with age or body mass index in either the control or study group. CONCLUSION: Serum CEA, periostin, and IDO levels were significantly higher in women with endometrial cancer than in those without cancer. These results may help identify new markers for diagnosing endometrial cancer.

The ability of various cerebroplacental ratio thresholds to predict adverse neonatal outcomes in term fetuses exhibiting late-onset fetal growth restriction.

OBJECTIVES: Our primary aim was to evaluate the ability of various cerebroplacental ratio (CPR) reference values suggested by the Fetal Medicine Foundation to predict adverse neonatal outcomes in term fetuses exhibiting late-onset fetal growth restriction (LOFGR). Our secondary aim was to evaluate the effectiveness of other obstetric Doppler parameters used to assess fetal well-being in terms of predicting adverse neonatal outcomes. METHODS: This was a retrospective cohort study of 317 pregnant women diagnosed with LOFGR at 37-40 weeks of gestation between January 1, 2016, and September 1, 2019. Receiver operating characteristic (ROC) curves were drawn to determine the predictive performance of CPR <1, CPR <5th or <10th percentile, and umbilical artery pulsatility (PI) >95th percentile in terms of predicting adverse neonatal outcomes. RESULTS: Pregnant women exhibiting LOFGR who gave birth in our clinic during the study period at a mean of 38 gestational weeks (minimum 37+0; maximum 40+6 weeks); the median CPR was 1.51 [interquartile range (IQR) 1.12-1.95] and median birthweight 2,350 g (IQR 2,125-2,575 g). The CPR <5th percentile best predicted adverse neonatal outcomes [area under the curve (AUC) 0.762, 95% confidence interval (CI) 0.672-0.853, p<0.0001] and CPR <1 was the worst predictor (AUC 0.630, 95% CI 0.515-0.745, p=0.021). Of other Doppler parameters, neither the umbilical artery systole/diastole ratio nor the mid-cerebral artery to peak systolic velocity ratio (MCA-PSV) predicted adverse neonatal outcomes (AUC 0.598, 95% CI 0.480-0.598, p=0.104; AUC 0.521, 95% CI 0.396-0.521, p=0.744 respectively). CONCLUSIONS: The CPR values below the 5th percentile better predicted adverse neonatal outcomes in pregnancies complicated by LOFGR than the UA PI and CPR <1 by using Fetal Medicine Foundation reference ranges.

COMPARISON OF TVUS, MRI, AND FROZEN SECTION METHODS IN PREOPERATIVE DETECTION OF MYOMETRIAL INVASION IN PATIENTS WITH ENDOMETRIAL CANCER.

We aimed to evaluate the depth of myometrial invasion preoperatively with transvaginal ultrasound, magnetic resonance imaging, and frozen section examination techniques in patients diagnosed with endometrial cancer. Our study included 65 patients. Transvaginal ultrasound and magnetic resonance imaging were performed in study patients in the preoperative period. Frozen section examination was performed in all hysterectomy samples obtained from all study patients. Data were analyzed with SPSS Statistics 22.0 program. The sensitivity of transvaginal ultrasound in determining the depth of myometrial invasion was 88.64%, specificity 90.48%, positive predictive value 95.12%, and negative predictive value 79.17%. For magnetic resonance imaging, the sensitivity was 63.64%, specificity 95.24%, positive predictive value 96.55%, and negative predictive value 55.56%. In addition to the frozen section examination, which is the gold standard in determining the myometrial invasion depth, transvaginal ultrasound and magnetic resonance imaging have become commonly used methods for this purpose in recent years. Ultrasound examination performed by an experienced specialist is superior to magnetic resonance imaging as it is fast, inexpensive, and associated with higher sensitivity.

Prediction of success of uterus-preserving management in women with placenta accreta spectrum (CON-PAS score): A multicenter international study.

OBJECTIVE: To create a model for prediction of success of uterine-preserving procedures in women with placenta accreta spectrum (PAS). METHODS: PAS-ID is a multicenter study that included 11 centers from 9 countries. Women with PAS, who were managed between January 1, 2010 and December 31, 2019, were retrospectively included. Data were split into model development and validation cohorts, and a prediction model was created using logistic regression. Main outcome was success of uterine preservation. RESULTS: Out of 797 women with PAS, 587 were eligible. Uterus-preserving procedures were successful in 469 patients (79.9%). Number of previous cesarean sections (CS) was inversely associated with management success (adjusted odds ratio [aOR] 0.02, 95% confidence interval [CI] 0.001-3.63 with five previous CS). Other variables were complete placental invasion (aOR 0.14, 95% CI 0.05-0.43), type of CS incision (aOR 0.04, 95% CI 0.01-0.25 for classical incision), compression sutures (aOR 2.48, 95% CI 1.00-6.16), accreta type (aOR 3.76, 95% CI 1.13-12.53), incising away from placenta (aOR 5.09, 95% CI 1.52-16.97), and uterine resection (aOR 102.57, 95% CI 3.97-2652.74). CONCLUSION: The present study provides a prediction model for success of uterine preservation, which may assist preoperative and intraoperative decisions, and promote incorporation of uterine preservation procedures in comprehensive PAS protocols.

Evaluation of second-trimester maternal serum betatrophin levels and lipid and carbohydrate metabolism parameters in patients with gestational diabetes mellitus.

OBJECTIVE: We investigated the role of betatrophin in the etiopathogenesis of gestational diabetes mellitus (GDM) and its association with lipid and carbohydrate metabolism in patients with GDM and normoglycemic pregnant women. MATERIALS AND METHODS: A total of 60 patients [30 pregnant women with GDM (study group) and 30 healthy age-, body mass index-, and gestational agematched pregnant women (control group)] were included in this study. Serum betatrophin, fasting glucose, insulin, glycated hemoglobin A1c (HbA1c), and C-peptide levels, as well as lipid parameters, were measured. RESULTS: Serum betatrophin, fasting glucose, HbA1c, insulin, and C-peptide levels were significantly higher in the GDM group than in the control group (p<0.001, p=0.009, p=0.013, p<0.001, and p<0.001, respectively). Levels of triglycerides and very-low-density lipoprotein cholesterol were significantly higher in the GDM group (p=0.020 and p=0.020, respectively), but total cholesterol and LDL cholesterol levels were similar in the two groups (p=0.810 and p=0.273, respectively). Betatrophin levels in the GDM group were correlated positively with insulin levels (r=0.336, p=0.009) and the homeostatic model assessment of insulin resistance (HOMA-IR) score (r=0.269, p=0.038), and negatively with the C-peptide levels (r=-0.399, p=0.002); they were not correlated with any other glucose or lipid parameters. Multivariate stepwise linear regression analysis demonstrated that insulin levels (ß=0.134, p=0.013) and the HOMA-IR score (ß=0.112, p=0.017) were associated independently with serum betatrophin levels. CONCLUSION: These results demonstrate that serum betatrophin levels were significantly higher in pregnant women with GDM than in normoglycemic pregnant women. The levels of betatrophin were correlated significantly with insulin resistance parameters, which is a key feature of GDM pathophysiology.

Relationship between guanosine triphosphate pathway and tetrahydrobiopterin in gestational diabetes mellitus.

PURPOSE: The present study assesses the change in tetrahydrobiopterin (BH4), one of the most important products in the guanosine triphosphate (GTP) pathway and in other parameters that might affect nitric oxide (NO) production, in gestational diabetes mellitus (GDM). METHODS: The study included 100 healthy pregnant women and 100 women diagnosed with GDM. Serum levels of neopterin, BH4 and NO were measured. The levels of endothelial nitric oxide synthase (eNOS), inducible nitric oxide synthase (iNOS) and guanosine triphosphate cyclohydrolase I (GCHI/GTPCH) gene expression were determined. RESULTS: It was found that diabetes led to an increase in neopterin and NO levels, and a decrease in BH4 levels. A stimulation was observed in eNOS gene expression in the GDM group when compared to the control group, while GCHI levels were found to decrease when compared to the control group. iNOS gene expression was detected in neither the healthy controls nor the patient group. CONCLUSIONS: Decreased NO bioavailability plays an important role in the progression of such macrovascular diseases as diabetes. BH4 levels decrease in diabetes patients, while the increased gene expression of GCHI reverses the diabetes-related BH4 deficiency and allows the endothelial cells to regain their ability to produce NO. Since GCHI is the rate-limiting enzyme in the biosynthesis of BH4, changes in GCHI levels directly affect the BH4 levels and the NO metabolism, leading to an increased risk of macrovascular complications. The significant increase in neopterin levels suggest that this is a potential biomarker for the early diagnosis of GDM.