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The ability of various cerebroplacental ratio thresholds to predict adverse neonatal outcomes in term fetuses exhibiting late-onset fetal growth restriction
(Walter De Gruyter Gmbh, 2021) Melekoglu, Rauf; Yilmaz, Ercan; Yasar, Seyma; Hatipoglu, Irem; Kahveci, Bekir; Sucu, Mete
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 lateonset 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.
Amnioinfusion vs. standard management for the second trimester PPROM: a systematic review and meta-analysis of observational studies and RCTs
(Taylor & Francis Ltd, 2023) Celik, Ebru; Yildiz, Abdullah Burak; Cekic, Sebile Guler; Unal, Ceren; Ayhan, Isil; Melekoglu, Rauf; Gursoy, Tugba
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 I (2) 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.
Analysis of prognostic factors in Grade 3 endometrioid type endometrial carcinoma
(Wiley, 2022) Sahin, Eda Adeviye; Toprak, Serhat; Sayal, Hasan Berkan; Ekinci, Tekin; Yilmaz, Ercan; Bakay, Kadir; Melekoglu, Rauf
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.
Assessing lipoxin-mediated inflammatory responses in the second trimester of pregnancy among women with obesity: A comprehensive analysis
(Galenos Publ House, 2023) Otlu, Oender; Melekoglu, Rauf; Kiran, Tugba Raika; Inceoglu, Feyza; Erenler, Ayse Sebnem
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-alpha), 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-alpha were quantified using enzyme-linked immunosorbent assay. Results: Plasma levels of LXA4 were notably lower in pregnant women with obesity, whereas levels of TNF-alpha 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-alpha 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.
Associations between second-trimester amniotic fluid levels of ADAMTS4, ADAMTS5, IL-6, and TNF-? and spontaneous preterm delivery in singleton pregnancies
(Walter De Gruyter Gmbh, 2019) Melekoglu, Rauf; Yilmaz, Ercan; Ciftci, Osman; Kafadar, Yusuf Taner; Celik, Ebru
Background: We investigated the roles of inflammatory cytokines and the A disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) family in the etiopathogenesis of spontaneous preterm delivery by comparing the ADAMTS4, ADAMTS5, interleukin (IL)-6, and tumor necrosis factor-alpha (TNF-alpha) levels in second-trimester amniotic fluid between pregnant women with preterm birth and term controls. Methods: All pregnant women who underwent second-trimester amniocentesis for genetic analysis between January 1, 2016, and January 1, 2018, were enrolled in this study. From this cohort, 22 patients who subsequently experienced spontaneous preterm delivery before 34 weeks of pregnancy formed the study group, and 22 age- and body mass index (BMI)-matched patients without preterm birth constituted the control group. Results: No significant differences were observed between the preterm birth and control groups in terms of age, BMI, obstetric history of preterm delivery, gestational age at amniocentesis, or indication for amniocentesis. The mean amniotic fluid levels of ADAMTS4 and ADAMTS5 were significantly increased in the preterm birth group compared to the control group (248.3 +/- 22.6 and 182.4 +/- 19.8 pg/mL, P = 0.012; and 198.6 +/- 21.6 and 159.1 +/- 21.7 pg/mL, P = 0.035, respectively). Significantly increased IL-6 and TNF-a levels were also detected in the amniotic fluid of women who experienced spontaneous preterm delivery, relative to controls (142.1 +/- 16.2 and 95.8 +/- 16.4 pg/mL, P < 0.001; and 139.4 +/- 12.5 and 89.6 +/- 11.2 pg/mL, P < 0.001, respectively). Conclusion: The results of this study imply that increased mid-trimester amniotic fluid levels of ADAMTS4, ADAMTS5, IL-6, and TNF-alpha play an important role in the pathophysiology of spontaneous preterm delivery.
Beneficial effects of curcumin and capsaicin on cyclophosphamide-induced premature ovarian failure in a rat model
(Bmc, 2018) Melekoglu, Rauf; Ciftci, Osman; Eraslan, Sevil; Cetin, Asli; Basak, Nese
Background: In recent years, cancer rates have been rising among reproductive-age women. Thus, chemotherapy exposure has become an important cause of premature ovarian failure (POF). There has been growing interest regarding the preservation and restoration of ovarian function before and after oncological treatment because of the reproductive risk of chemotherapeutics and improved long-term survival of cancer patients. In this study, we sought to analyze the effects of curcumin (CRC) and capsaicin (CPS) on cyclophosphamide-induced POF in a rat model. Methods: POF in rats was induced by intraperitoneal injection of 200 mg/kg cyclophosphamide on day 1 and then 8 mg/kg/day for the following 14 days. After 14 days of cyclophosphamide administration, rats were randomly divided into three groups as follows (n = 10/group): POF, POF + CRC (100 mg/kg/day), and POF + CPS (0.5 mg/kg/day) to determine the effects of CRC and CPS on the cyclophosphamide-induced POF rat model. Biochemical, hormonal, and histopathological evaluations were performed on blood and tissue samples 14 days after the CRC and CPS treatments. Results: Malonaldehyde levels were significantly reduced, and glutathione levels and superoxide dismutase activity were significantly increased, in ovarian tissues in the POF + CRC and POF + CPS groups compared with the POF group. In the POF group, we observed hemorrhage and prominent mononuclear cell infiltration beneath the germinative epithelium, vascular congestion in ovarian stroma, hemorrhage around the corpus luteum, and atresia in ovarian follicles. This histopathological damage was significantly improved by treatment with CRC and CPS. There was a significant reduction in serum follicle-stimulating hormone and luteinizing hormone levels in rats treated with CRC and CPS compared with the POF group. Moreover, the levels of estradiol and anti-mullerian hormone in rats treated with CRC and CPS were significantly increased compared with the control group. Conclusions: In conclusion, CRC and CPS treatment of rats with cyclophosphamide-induced POF had a beneficial effect on reducing ovarian damage by improving tissue oxidative stress marker levels, ovarian reserve marker levels, and histopathological parameters. The significant improvements in ovarian tissue histopathological damage and hormonal levels detected in this study indicate that treatment with CRC or CPS might be a conservative treatment approach for cyclophosphamide-induced POF.
The beneficial effects of Montelukast against 2,3,7,8-tetrachlorodibenzo-p-dioxin toxicity in female reproductive system in rats
(Acta Cirurgica Brasileira, 2016) Melekoglu, Rauf; Ciftci, Osman; Cetin, Ash; Basak, Nese; Celik, Ebru
PURPOSE: To determine the toxic effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on reproductive system and the beneficial effects of Montelukast (ML) with histological and biochemical analysis. METHODS: Rats were randomly divided into four equal groups (control, TCDD, ML and TCDD+ML). Tissue samples were collected on day 60 and oxidative status and histological alterations were analyzed. RESULTS: The results showed a significant increase in oxidative and histological damage on uterine and ovarian tissues. Otherwise, the oxidative and histological damages caused by TCDD were prevented with ML treatment. CONCLUSION: The toxic effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin on female reproductive system were reversed with Montelukast treatment. Therefore, we claimed that ML treatment might be useful for TCDD toxicity.
The beneficial effects of nerolidol and hesperidin on surgically induced endometriosis in a rat model
(Taylor & Francis Ltd, 2018) Melekoglu, Rauf; Ciftci, Osman; Eraslan, Sevil; Cetin, Asli; Basak, Nese
The objective of this article is to analyze the effects of nerolidol and hesperidin treatment on surgically induced endometriosis in a rat model. Endometriosis was induced in 24 healthy adult female Wistar albino rats via homologous uterine horn transplantation. Three operations were performed on each rat. After the second operation, the rats were randomized into control, nerolidol, and hesperidin treatment groups, and medications were administered for 2 weeks. The effects of the drugs on the endometriotic foci were evaluated after the third operation. Compared with the endometriosis control group, the average volume of the lesions was significantly lower in rats treated with hesperidin and nerolidol. Malondialdehyde levels were significantly reduced in the nerolidol-treated group, and glutathione levels and superoxide dismutase activity were significantly elevated in the endometriotic foci of both the hesperidin- and nerolidol-treated groups compared with the endometriosis group. Hesperidin and nerolidol treatment also improved histological parameters, such as hemorrhage, vascular congestion, necrosis, and inflammatory cell infiltration in the endometriotic foci. The results of this study demonstrated that treatment with the potent antioxidants nerolidol and hesperidin caused a significant regression of surgically induced endometriotic foci in rats.
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
(Wiley, 2021) Unuvar, Songul; Melekoglu, Rauf; Turkmen, Nese B.; Yilmaz, Ercan; Yasar, Seyma; Yuce, Hande
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.
COMPARISON OF TVUS, MRI, AND FROZEN SECTION METHODS IN PREOPERATIVE DETECTION OF MYOMETRIAL INVASION IN PATIENTS WITH ENDOMETRIAL CANCER
(Sestre Milosrdnice Univ Hospital, 2021) Kural, Hasim; Yilmaz, Ercan; Melekoglu, Rauf; Akatli, Aysenur; Karaca, Leyla
We aimed to evaluate the depth of myometrial invasion preoperatively with trans vaginal 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.
Determination of biomarker candidates for the placenta accreta spectrum by plasma proteomic analysis
(Nature Portfolio, 2024) Melekoglu, Rauf; Yasar, Seyma; Colak, Cemil; Kasap, Murat; Dogan, Umran Karabulut; Yologlu, Saim; Yilmaz, Ercan
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.
The effect of advanced maternal age on perinatal outcomes in nulliparous singleton pregnancies
(Bmc, 2018) Kahveci, Bekir; Melekoglu, Rauf; Evruke, Ismail Cuneyt; Cetin, Cihan
Background: Pregnancy at advanced maternal age has become more common in both developed and developing countries over the last decades. The association between adverse perinatal outcomes and advanced maternal age has been a matter of controversy in several studies. The objective of this study is to investigate the impact of advanced maternal age on perinatal and neonatal outcomes of nulliparous singleton pregnancies. Methods: Records of patients admitted to the Department of Obstetrics and Gynecology, University of Cukurova School of Medicine, between January 2011 and July 2015 for routine mid-trimester fetal ultrasonography were retrospectively reviewed. The control (age: 18-34 years), advanced maternal age (35-39 years), and very advanced maternal age (>40 years) groups included 471, 399, and 87 women, respectively. Results: Gestational diabetes, gestational hypertension, and cesarean delivery rates were more common in the very advanced maternal age group, with compared with the advanced maternal age and the younger age group. There were no significant differences in regarding rates of spontaneous preterm delivery before 34 weeks of gestation, prolonged rupture of membranes, large for gestational age infants, and operative vaginal delivery rates between the groups. Also, there were no significant differences regarding in APGAR scores, the rate of low birth weight infants, and neonatal morbidity rates between the groups. However, admission to the neonatal intensive care unit requirement was more common in the two advanced maternal age groups compared with the control group. Conclusion: Advanced maternal age is a risk factor for gestational diabetes mellitus, gestational hypertension, preeclampsia, small for gestational age infants, spontaneous late preterm delivery, and cesarean section, with significant potential clinical implications.
The Effect of Prognostic Factors and Adjuvant Radiotherapy on Survival in Patients with High-Grade Early-Stage Endometrial Cancer: A Retrospective Clinical Study
(Int Scientific Information, Inc, 2019) Yilmaz, Ercan; Gurocak, Simay; Melekoglu, Rauf; Koleli, Isil; Faydali, Simge; Temelli, Oztun; Yar, Tuba
Background: This retrospective clinical study aimed to investigate the effect of prognostic factors and adjuvant radiotherapy in patients with high-grade early-stage endometrial cancer on overall survival (OS) and disease-free survival (DES). Material/Methods: The medical records of patients diagnosed with high-grade, early stage (I or II) endometrial adenocarcinoma who had received adjuvant radiotherapy after surgery were reviewed. Results: Seventy-nine patients included 39 patients (49.4%) with stage II endometrial cancer, 25 patients (31.6%) with histologic grade 3 tumors, and 47 patients (59.5%) with endometrial cancer showing lymphovascular space invasion (LVSI). There were 45 patients (57.0%) who received external pelvic radiotherapy with an average dose of 46.0 Gy (range, 11.2-50.4 Gy), and 34 patients (43.0%) received vaginal brachytherapy (VBT) with an average dose of 21.5 Gy (range, 10-36 Gy). Multivariate analysis showed that tumor stage (HR, 4.066; 95% CI, 1.227-13.467; p=0.022) and histologic grade (HR, 16.652; 95% CI, 4.430-62.589; p<0.001) were independent predictors for OS. Increased serum CA-125 levels (HR, 1.136; 95% CI, 0.995-1.653; p=0.047) and histologic grade (HR, 3.236; 95% CI, 1.107-15.156; p=0.015) were independent predictors for DES. Adjuvant radiotherapy was not found to be significantly associated with improved OS (HR, 1.259; 95% CI, 0.518-3.058; p=0.612) or DES (HR, 1.056; 95% CI, 0.994-1.123; p=0.078). Conclusions: This retrospective study showed that in high-grade early-stage endometrial cancer treated with postoperative adjuvant radiotherapy, independent predictors for OS were tumor stage and grade. Adjuvant radiotherapy was not associated with improved OS or DES.
The Effects of Body Mass Index on Second-Trimester Amniotic Fluid Cytokine and Matrix Metalloproteinase Levels
(Karger, 2018) Melekoglu, Rauf; Ciftci, Osman; Eraslan, Sevil; Basak, Nese; Celik, Ebru
Aim: The aim of this study was to determine the effects of obesity on amniotic fluid (AF) inflammatory markers in second-trimester AF, testing the hypothesis that there is a relationship between maternal body mass index (BMI) and fetal inflammatory exposure. Methods: AF was obtained from 84 singleton pregnant women undergoing elective amniocentesis for karyotype analysis at 16-24 weeks of gestation between April 2014 and May 2016. The cell-free AF was used to analyze interleukin (IL)-1 beta and IL-6, and matrix metalloproteinase (MMP)-1, MMP-6, and MMP-13. Results: IL-1 beta levels were significantly higher in class II-III obese patients than in class I obese, overweight, and normal weight patients (14.68 +/- 1.37 vs. 13.34 +/- 1.86 vs. 13.00 +/- 2.22 vs. 10.78 +/- 1.92, respectively; p < 0.05). IL-6 levels were lowest in the normal weight group and highest in class II-III obese patients. MMP-1, MMP-6, and MMP-13 levels were also significantly higher in class II-III obese patients than in the other groups. Conclusion: This study demonstrated that the fetuses of class II-III obese women are exposed in utero to higher cytokine and MMP levels than fetuses of lean women. Modification of current cutoff levels of intra-amniotic cytokines and MMPs according to the BMI could improve the accuracy of the prenatal diagnosis of intra-amniotic infection and inflammation. (C) 2017 S. Karger AG, Basel
Endometrial Cancer Individualized Scoring System (ECISS): A machine learning-based prediction model of endometrial cancer prognosis
(Wiley, 2023) Shazly, Sherif A.; Coronado, Pluvio J.; Yilmaz, Ercan; Melekoglu, Rauf; Sahin, Hanifi; Giannella, Luca; Ciavattini, Andrea
ObjectiveTo establish a prognostic model for endometrial cancer (EC) that individualizes a risk and management plan per patient and disease characteristics. MethodsA 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). ResultsOf 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. ConclusionThe Endometrial Cancer Individualized Scoring System (ECISS) is a novel machine learning tool assessing patient-specific survival probability with high accuracy.
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
(Galenos Yayincilik, 2022) Melekoglu, Rauf; Yasar, Seyma; Celik, Nesibe Zeyveli; Ozdemir, Halis
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.
Evaluation of Lipocalin-2 and Metalloproteinase-9 Gene Expressions in Early-Stage Endometrial Cancer
(Wiley, 2023) Unuvar, Songul; Melekoglu, Rauf; Bulut, Ezgi; Dogan, Aysegul; Turkmen, Nese Basak; Yuce, Hande; Yilmaz, Ercan
[Abstract Not Available]
Evaluation of second trimester amniotic fluid ADAMTS4, ADAMTS5, interleukin-6 and tumor necrosis factor-? levels in patients with gestational diabetes mellitus
(Wiley, 2019) Melekoglu, Rauf; Ciftci, Osman; Celik, Ebru; Yilmaz, Ercan; Bastemur, Ayse G.
Aim To test the hypothesis that altered A Disintegrin and Metalloproteinase Domains with Thrombospondins motifs (ADAMTS) is implicated in the etiopathogenesis of gestational diabetes mellitus (GDM). Methods All pregnant women who underwent elective amniocentesis for karyotype analysis between January 1, 2016, and January 1, 2018, were included in this study. From this cohort, the study group consisting of 20 patients diagnosed with GDM was selected and compared against a control group consisting of 20 age- and body mass index (BMI)-matched patients without GDM. ADAMTS4, ADAMTS5, interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-alpha) levels were compared in the second trimester amniotic fluid of patients with GDM and normoglycemic pregnant women. Results No significant differences were observed between GDM and control groups regarding age, BMI, gestational age at amniocentesis and indication for amniocentesis. Mean amniotic fluid ADAMTS4 and ADAMTS5 levels were significantly increased in the GDM group compared with the control group (253.5 +/- 18.7 pg/mL and 188.5 +/- 21.3 pg/mL, P < 0.001; 192.9 +/- 16.4 pg/mL and 154.8 +/- 19.9 pg/mL, P = 0.021, respectively). Significant increases in IL-6 and TNF-alpha levels were also detected in the amniotic fluid of GDM patients relative to controls (136.2 +/- 17.3 pg/mL and 98.3 +/- 11.5 pg/mL, P < 0.001; 154.2 +/- 12.5 pg/mL and 86.2 +/- 10.8 pg/mL, P < 0.001, respectively). Conclusion The data presented here suggest that increased levels of ADAMTS4, ADAMTS5, IL-6 and TNF-alpha may play an important role in the progression of GDM.
Evaluation of second trimester plasma lipoxin A4, VEGFR-1, IL-6, and TNF-a levels in pregnant women with gestational diabetes mellitus
(De Gruyter Poland Sp Z O O, 2023) Kiran, Tugba Raika; Melekoglu, Rauf; Otlu, Onder; Inceoglu, Feyza; Karabulut, Ercan; Erenler, Ayse Sebnem
In this study, our objective was to explore the association between gestational diabetes mellitus (GDM) and second trimester maternal plasma levels of lipoxin A4 (LXA4), along with proinflammatory markers such as interleukin-6 (IL-6) and tumour necrosis factor alpha (TNF-a), and the anti-angiogenic factor vascular endothelial growth factor receptor 1 (VEGFR-1) in pregnant women. The study included a cohort of 30 pregnant women with GDM and a control group of 30 normoglycaemic pregnant women matched for age, body mass index, and gestational age. Plasma samples were collected and analysed by enzyme-linked immunosorbent assay to assess specific biomarkers. The GDM group had significantly lower levels of LXA4 and higher levels of TNF-a and VEGFR-1 compared to the control group (p = 0.038, p = 0.025, and p = 0.002, respectively). A statistically significant decrease in the LXA4/TNF-a ratio was observed in the GDM group (p = 0.004). The results suggest that each unit decrease in the LXA4/TNF-a ratio is associated with a 1.280-fold increase in the risk of GDM. These findings suggest a potential diagnostic role for the LXA4/TNFa ratio as a marker for women with GDM. This work provides new insights into the pathogenesis of GDM and highlights the important interplay between inflammation and metabolic dysregulation.
Evaluation of second-trimester maternal serum betatrophin levels and lipid and carbohydrate metabolism parameters in patients with gestational diabetes mellitus
(Galenos Publ House, 2020) Bulmus, Funda Gulcu; Melekoglu, Rauf; Gursu, Mehmet Ferit; Bagci, Helin; Kavak, Ebru Celik; Akyol, Alpaslan
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 age-matched 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 (beta=0.134, p=0.013) and the HOMA-IR score (beta=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.

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