Role of increased plasminogen activator inhibitor-1 and vitronectin in gestational diabetes mellitus.

OBJECTIVE: The aim of this study was to analyze the second-trimester levels of vitronectin and plasminogen activator inhibitor-1 in gestational diabetes mellitus. METHODS: This study was conducted between September 2020 and December 2020 at the University of Health Sciences, Bursa Yuksek Ihtisas Research and Training Hospital, Department of Obstetrics and Gynecology. A total of 30 pregnant women with gestational diabetes mellitus and 60 healthy controls between 24 and 27/6 weeks of gestation were included. The inclusion criteria were as follows: being between 18 and 45 years old and 24-27/6 gestational weeks, having singleton pregnancy, diagnosed with gestational diabetes mellitus by using a two-step challenge test. The exclusion criteria of this study were as follows: chronic inflammatory or infectious disease, fasting blood glucose>126 mg/dL, intolerance to glucose tolerance testing, abnormal liver or kidney function tests, as well as pregnancy with pre-gestational diabetes history of adverse perinatal outcomes. Serum vitronectin and plasminogen activator inhibitor-1 levels were measured using the enzyme-linked immunosorbent assay method. RESULTS: Vitronectin and plasminogen activator inhibitor-1 levels were higher in the gestational diabetes mellitus group compared with controls [91.85 (23.08) vs. 80.10 (39.18) ng/mL, for vitronectin and 6.50 (1.05) vs. 4.35(1.0) ng/mL, for plasminogen activator inhibitor-1 (for both p<0.001)]. vitronectin >84.7 ng/mL was found to predict gestational diabetes mellitus with a sensitivity of 70% and specificity of 63.3%. Moreover, vitronectin had a significant positive correlation with fasting blood glucose (r=0.476, p<0.001), postprandial blood glucose (r=0.489, p<0.001), HbA1c (r=0.713, p<0.001), and plasminogen activator inhibitor-1 (r=0.586, p<0.001). CONCLUSION: This study revealed that second-trimester vitronectin and plasminogen activator inhibitor-1 are increased in gestational diabetes mellitus and vitronectin could be a candidate for the prediction of gestational diabetes mellitus.

Role of increased plasminogen activator inhibitor-1 and vitronectin in gestational diabetes mellitus

SUMMARY OBJECTIVE: The aim of this study was to analyze the second-trimester levels of vitronectin and plasminogen activator inhibitor-1 in gestational diabetes mellitus. METHODS: This study was conducted between September 2020 and December 2020 at the University of Health Sciences, Bursa Yuksek Ihtisas Research and Training Hospital, Department of Obstetrics and Gynecology. A total of 30 pregnant women with gestational diabetes mellitus and 60 healthy controls between 24 and 27/6 weeks of gestation were included. The inclusion criteria were as follows: being between 18 and 45 years old and 24-27/6 gestational weeks, having singleton pregnancy, diagnosed with gestational diabetes mellitus by using a two-step challenge test. The exclusion criteria of this study were as follows: chronic inflammatory or infectious disease, fasting blood glucose>126 mg/dL, intolerance to glucose tolerance testing, abnormal liver or kidney function tests, as well as pregnancy with pre-gestational diabetes history of adverse perinatal outcomes. Serum vitronectin and plasminogen activator inhibitor-1 levels were measured using the enzyme-linked immunosorbent assay method. RESULTS: Vitronectin and plasminogen activator inhibitor-1 levels were higher in the gestational diabetes mellitus group compared with controls [91.85 (23.08) vs. 80.10 (39.18) ng/mL, for vitronectin and 6.50 (1.05) vs. 4.35(1.0) ng/mL, for plasminogen activator inhibitor-1 (for both p<0.001)]. vitronectin >84.7 ng/mL was found to predict gestational diabetes mellitus with a sensitivity of 70% and specificity of 63.3%. Moreover, vitronectin had a significant positive correlation with fasting blood glucose (r=0.476, p<0.001), postprandial blood glucose (r=0.489, p<0.001), HbA1c (r=0.713, p<0.001), and plasminogen activator inhibitor-1 (r=0.586, p<0.001). CONCLUSION: This study revealed that second-trimester vitronectin and plasminogen activator inhibitor-1 are increased in gestational diabetes mellitus and vitronectin could be a candidate for the prediction of gestational diabetes mellitus.

Angiotensin-Converting Enzyme (ACE) level, but not ACE gene polymorphism, is associated with prognosis of COVID-19 infection: Implications for diabetes and hypertension.

BACKGROUND: The renin-angiotensin-aldosterone system was shown to be activated in severe COVID-19 infection. We aimed to investigate the relationship between angiotensin converting enzyme (ACE) levels, ACE gene polymorphism, type 2 diabetes (T2DM), and hypertension (HT) and the prognosis of COVID-19 infection. METHODS: This cross-sectional study analyzed the clinical features of adult patients with SARS-CoV-2 infection. ACE gene analysis and ACE level measurements were performed. The patients were grouped according to ACE gene polymorphism (DD, ID or II), disease severity (mild, moderate, or severe), and the use of dipeptidyl peptidase-4 enzyme inhibitor (DPP4i), ACE-inhibitor (ACEi) or angiotensin receptor blocker (ARB). Intensive care unit (ICU) admissions and mortality were also recorded. RESULTS: A total of 266 patients were enrolled. Gene analysis detected DD polymorphism in the ACE 1 gene in 32.7% (n = 87), ID in 51.5% (n = 137), and II in 15.8% (n = 42) of the patients. ACE gene polymorphisms were not associated with disease severity, ICU admission, or mortality. ACE levels were higher in patients who died (p = 0.004) or were admitted to the ICU (p<0.001) and in those with severe disease compared to cases with mild (p = 0.023) or moderate (p<0.001) disease. HT, T2DM, and ACEi/ARB or DPP4i use were not associated with mortality or ICU admission. ACE levels were similar in patients with or without HT (p = 0.374) and with HT using or not using ACEi/ARB (p = 0.999). They were also similar in patients with and without T2DM (p = 0.062) and in those with and without DPP4i treatment (p = 0.427). ACE level was a weak predictor of mortality but an important predictor of ICU admission. It predicted ICU admission in total (cutoff value >37.092 ng/mL, AUC: 0.775, p<0.001). CONCLUSION: Our findings suggest that higher ACE levels, but not ACE gene polymorphism, ACEi/ARB or DPP4i use, were associated with the prognosis of COVID-19 infection. The presence of HT and T2DM and ACEi/ARB or DPP4i use were not associated with mortality or ICU admission.

The predictive value of HALP score and systemic immune inflammation (SII) index in hyperemesis gravidarum.

AIM: Hyperemesis gravidarum (HG) is one of the most common serious diseases in early pregnancy. This study aimed to investigate the clinical significance of hemoglobin, albumin, lymphocyte, and platelet (HALP) score and systemic immune inflammation (SII) index in the presence and severity of HG. METHODS: This retrospective case-control study was conducted in a training and educational university hospital between January 2019 and July 2022. A total of 521 pregnant women, of whom 360 were diagnosed with HG at 6-14 weeks of gestation and 161 were low-risk pregnancies, were included in the study. Patients' demographic characteristics and laboratory parameters were recorded. Patients with HG were divided into three categories: mild (n = 160), moderate (n = 116), and severe (n = 84), according to disease severity. The modified PUQE scoring was used to determine the severity of HG. RESULTS: The mean age of the patients was 27.6 (16-40) years. We divided the pregnant women into the control group and HG group. The HALP score was significantly lower in the HG group (average, 2.8 ± 1.3), whereas the SII index was found to be significantly higher (average, 895.8 ± 458.1). A negative correlation was found between the increase in the severity of HG and HALP score. The HALP score was the lower in severe HG (mean, 2.16 ± 0.81) and was significantly different from other HG categories (p < 0.01). Moreover, a positive correlation was noted between increased HG severity and SII index levels. The SII index was higher in the severe HG group and was significantly different from the others (1001.2 ± 437.2) (p < 0.01). CONCLUSIONS: The HALP score and SII index can be useful, cost-effective, and easily accessible objective biomarkers to predict the presence and severity of HG.

Fibrinogen Levels and Total Serum Bile Acids in Intrahepatic Cholestasis of Pregnancy.

OBJECTIVE: To determine the role of complete blood count and coagulation function factors as inflammatory markers in intrahepatic cholestasis of pregnancy (ICP). STUDY DESIGN: Descriptive, analytical study. PLACE AND DURATION OF STUDY: Department of Obstetrics and Gynecology, Bursa Yüksek Ihtisas Training and Research Hospital, Bursa, Turkey, between January 2018 and 2021. METHODOLOGY: This study was conducted with a total of 200 pregnant women, 80 with ICP and 120 control healthy pregnant women. The diagnosis of ICP was made based on elevated liver enzymes and bile acids (≥10 µmol/L) and pruritis. Routine complete blood count parameters and coagulation function tests were compared between both groups. ROC analyses were used to analyse the predictive value of fibrinogen levels in ICP. Spearman's rank correlation analysis assessed the correlation between fasting bile acid value and complete blood count and coagulation parameters. RESULTS: Neutrophil-lymphocyte ratio (NLR), Platelet count, and Platecrit levels were significantly higher in the ICP group, and red blood cell distribution width (RDW) was lower than in the healthy group (p <0.05). The median plasma fibrinogen value was 571 mg/dl which was significantly higher in pregnant women with cholestasis (p <0.001). The prothrombin time and international normalized ratio (INR) values were also significantly different in each group (p <0.001 and 0.013, respectively). In addition, platelet distribution width (PDW), plasma fibrinogen, and prothrombin time (PT) showed significant association with the bile acid values (p values=0.007, 0.03, and 0.04 respectively). Each 1-unit elevation of the fibrinogen increased the risk of cholestasis by 1.02 times. There was a positive correlation of 0.24-fold between the plasma fibrinogen value and acids. CONCLUSION: The plasma fibrinogen value was the highest predictor of cholestasis diagnosis by analyzing blood parameters. Elevated fibrinogen levels correlated with bile acid levels, can potentially detect ICP. KEY WORDS: Bile acids, Cholestasis, Coagulation function parameters, Fibrinogen levels, Inflammation.

Are women diagnosed with early pregnancy loss at risk for anxiety, depression, and perinatal grief?

OBJECTIVES: To examine the effects of early pregnancy loss on emotions such as depression, grief, or a sense of hopelessness, while investigating different types of diagnoses, hospital stays, and treatments. METHODS: A prospective cohort epidemiological study was carried out in Bursa Yuksek Ihtisas Training and Research Hospital, Bursa, Turkey, between January and September 2019. The study included women diagnosed with early pregnancy loss classified into 3 groups: missed abortus, anembryonic pregnancy, and spontaneous abortion. The patients were screened via the Spielberger state-anxiety inventory (STAI-1) before initiating treatment. The Edinburgh postpartum depression scale (EPDS) and Perinatal Grief Scale (PGS) were also carried out in the first week of their hospital discharge. RESULTS: The study was carried out with a total of 116 patients. The median gestational week of the patients was calculated at 9, their median hospital stay was 2 days, and their median dose of misoprostol was 800 mcg. The STAI-1 revealed that median values computed for women in all groups indicated moderate anxiety. The EDPS also demonstrated depression-positive median values for women in all 3 groups (EPDS>13). However, no statistically significant difference was noted in comparisons of the 3 groups apropos STAI-1, EPDS, and PGS. CONCLUSION: Moderate anxiety, depressed mood, and perinatal grief were found in women diagnosed with early pregnancy loss, regardless of the type of abortion.

Comparing the levels of CTLA-4-dependent biological defects in patients with LRBA deficiency and CTLA-4 insufficiency.

BACKGROUND: Lipopolysaccharide-responsive beige-like anchor protein (LRBA) deficiency and cytotoxic T-lymphocyte protein-4 (CTLA-4) insufficiency are recently described disorders that present with susceptibility to infections, autoimmunity, and lymphoproliferation. Clinical and immunological comparisons of the diseases with long-term follow-up have not been previously reported. We sought to compare the clinical and laboratory manifestations of both diseases and investigate the role of flow cytometry in predicting the genetic defect in patients with LRBA deficiency and CTLA-4 insufficiency. METHODS: Patients were evaluated clinically with laboratory assessments for lymphocyte subsets, T follicular helper cells (TFH ), LRBA expression, and expression of CD25, FOXP3, and CTLA4 in regulatory T cells (Tregs) at baseline and 16 h post-stimulation. RESULTS: LRBA-deficient patients (n = 29) showed significantly early age of symptom onset, higher rates of pneumonia, autoimmunity, chronic diarrhea, and failure to thrive compared to CTLA-4 insufficiency (n = 12). In total, 29 patients received abatacept with favorable responses and the overall survival probability was not different between transplanted versus non-transplanted patients in LRBA deficiency. Meanwhile, higher probability of survival was observed in CTLA-4-insufficient patients (p = 0.04). The T-cell subsets showed more deviation to memory cells in CTLA-4-insufficiency, accompanied by low percentages of Treg and dysregulated cTFH cells response in both diseases. Cumulative numbers of autoimmunities positively correlated with cTFH frequencies. Baseline CTLA-4 expression was significantly diminished in LRBA deficiency and CTLA-4 insufficiency, but significant induction in CTLA-4 was observed after short-term T-cell stimulation in LRBA deficiency and controls, while this elevation was less in CTLA-4 insufficiency, allowing to differentiate this disease from LRBA deficiency with high sensitivity (87.5%) and specificity (90%). CONCLUSION: This cohort provided detailed clinical and laboratory comparisons for LRBA deficiency and CTLA-4 insufficiency. The flow cytometric approach is useful in predicting the defective gene; thus, targeted sequencing can be conducted to provide rapid diagnosis and treatment for these diseases impacting the CTLA-4 pathway.

Effects of vitamin D receptor gene polymorphisms on the prognosis of COVID-19.

PURPOSE: Vitamin D deficiency has emerged as another potential risk factor for coronavirus disease (COVID-19) due to the immunomodulatory effects of 25 hydroxyvitamin D [25 (OH)D]. Vitamin D receptor (VDR) gene polymorphisms such as Fok I, Bsm I, Apa I, and Taq I are also associated with different courses of viral infections. This study aimed to evaluate the association between the VDR gene polymorphism at Fok I, Taq I, Bsm I, and Apa I genotypes and the prognosis of COVID-19 in respect to vitamin D deficiency. METHODS: Two-hundred ninety-seven patients with COVID-19 were enrolled. Serum 25 (OH)D levels were measured. Four variant regions of the VDR gene, FokI, BsmI, ApaI, and TaqI were determined. RESULTS: Eighty-three percent of subjects had vitamin D deficiency, and 40.7% of the whole group had severe deficiency. Median 25 (OH)D level was 11.97 ng/ml. Vitamin D levels were not related to inflammatory markers, disease severity, admission to intensive care unit (ICU), and mortality. While disease severity was related to Fok I Ff genotype, it was Taq TT genotype for ICU admission. Moreover, the ApaI aa genotype was common among the patients who were died. None of the deceased subjects had the Fok I FF genotype. CONCLUSION: 25 (OH)D levels were not related to the severity and mortality of COVID-19. VDR gene polymorphisms are independently associated with the severity of COVID-19 and the survival of patients.

The role of transvaginal color doppler indices to predict malignancy in abnormal uterine bleeding according to PALM-COEIN classification.

INTRODUCTION: The objective of this study is to analyze the differences in transvaginal color Doppler parameters in premenopasual women with abnormal uterine bleeding (AUB) among PALM-COEIN groups. MATERIALS AND METHOD: This cross-sectional study was performed in a training and educational hospital, included 147 premenopausal women with AUB. Patients were divided into four groups according to PALM-COEIN. All subjects were evaluated by transvaginal Doppler sonography and uterine artery (UA) pulsatility and resistive indexes (PI, RI) were calculated then compared. RESULTS: Four groups named AUB-P, AUB-E, AUB-M and AUB-O included 39, 30, 32 and 46 patients, respectively. The mean age of patients was 44.82 (35-55 years), EC rate was 3.4 %. UA-PI was lower in the AUB-M group compared with AUB-P and AUB-O (p < 0.001). UA-RI was different among gruops (p < 0.001). UA-RI was lowest in the AUB-M, and highest in the AUB-O (0.60 ± 0.15; 0.85 ± 0.05 respectively). The cut-off values of ET, UA-PI and UA-RI for detecting AUB-M were 13.5, 1.55 and 0.71 respectively. CONCLUSION: Transvaginal color Doppler sonography may be beneficial in detecting the etiology of AUB in premenopausal women.

Assessment of relationship between serum vascular adhesion protein-1 (VAP-1) and gestational diabetes mellitus.

Purpose: VAP-1 plays a crucial role in inflammation, oxidative stress and endothelial dysfunction which are main pathophysiologic mechanisms for gestational diabetes. We aimed to determine serum VAP-1 levels, assess its diagnostic value and correlation with clinical parameters in gestational diabetes.Methods: A total of 60 pregnant women with gestational diabetes and 75 healthy pregnant women between 24-28th gestational weeks between January-June 2017 were included. Pregnant women were screened for gestational diabetes by two-step protocol. Demographic, clinical and laboratory parameters of patients were recorded. VAP-1 was measured using an enzyme-linked immunosorbent assay method.Results: Gestational diabetes group had higher fasting and postprandial glucose, HbA1c, neutrophil-to-lymphocyte-ratio, platelet-to-lymphocyte-ratio, plateletcrit and C-reactive protein. Furthermore, VAP-1 levels were higher in gestational diabetes (3.35 ± 1.52 vs 2.2 ± 0.74; p < 0.001). VAP-1 levels >2.315 could predict gestational diabetes with a sensitivity of 70% and specificity of 65.3%. VAP-1 was correlated with clinical follow-up parameters such as fasting glucose (r = 0.473, p < 0.001), postprandial glucose (r = 0.416, p < 0.001), HbA1c (r = 0.462, p < 0.001) and inflammatory biomarkers such as platelet-to-lymphocyte-ratio (r = 0.254, p = 0.04), neutrophil-to-lymphocyte-ratio (r = 0.375, p = 0.003) and C-reactive protein (r = 0.306, p = 0.017).Conclusions: Elevated VAP-1 levels in gestational diabetes correlated with clinical follow-up and inflammatory markers may suggest the pathogenetic role of VAP-1 in gestational diabetes. Hence, we think that VAP-1 could be a promising marker for the prediction of gestational diabetes.

Is pregnancy associated plasma protein-A (PAPP-A) a marker for adverse perinatal outcomes in preterm isolated oligohydramnios cases?

OBJECTIVE: Isolated oligohydramnios is defined as an amniotic fluid index below five centimeter with no other coexisting condition. There are still controversies about the management and pregnancy outcomes. A marker predicting these is crucial. Low pregnancy associated plasma protein-A levels were reported to be related with adverse pregnancy outcomes. We aimed to determine the role of first trimester pregnancy associated plasma protein-A for poor outcomes in preterm isolated oligohydramnios cases. MATERIAL AND METHODS: Fifty-one patients with singleton pregnancies diagnosed as isolated oligohydramnios at 28/0-36/6 weeks of gestation and 110 gestational age matched healthy controls between January and December 2015 were included. Maternal age, gestational age at delivery, mode of delivery, indication for cesarean section, Apgar scores at first and fifth minutes, birth weight, neonatal intensive care unit admission and mortality were recorded. Pregnancy associated plasma protein-A levels were compared between groups and its role in adverse perinatal outcomes was evaluated. RESULTS: Pregnancy associated plasma protein-A levels and pregnancy outcomes were similar in two groups (p > 0.050) except birth weight, gestational age at delivery and presence of fetal distress. Pregnancy associated plasma protein-A levels did not differ in terms of delivery mode, presence of fetal distress, first and fifth minutes Apgar scores and neonatal intensive care unit admission (p = 0.323,0.650,0.990,0.112,0.853). Also, it was not determined as a risk factor for cesarean section, presence of fetal distress, low Apgar scores and neonatal intensive care unit admission. CONCLUSION: Pregnancy associated plasma protein-A, a well-known prognostic factor for some of high risk pregnancy conditions, may not be used as a marker in preterm isolated oligohydramnios cases.