Are changes in olanzapine-induced liver enzyme levels associated with GSTT1, GSTM1, GSTP1, and OGG1 gene polymorphisms?

Olanzapine treatment sometimes produces transient liver biochemistry abnormalities, and such drug-induced liver injuries are mainly monitored by measuring blood levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), whereas alpha-glutathione-S-transferase (α-GST) is not routinely measured in clinics, even though it can serve as an earlier and more specific biomarker of liver damage. Susceptibility to drug-induced liver injury can much depend on the gene polymorphisms regulating the activity of DNA detoxification and repair enzymes. The aim of this study was to evaluate which of the three liver enzymes - α-GST, ALT, and AST - is the most sensitive biomarker of olanzapine-induced liver injury and how their blood levels are affected by the GSTT1, GSTM1, GSTP1, and OGG1 gene polymorphisms in 30 olanzapine-treated patients. Contrary to our hypothesis, the increase in serum α-GST levels was not significantly greater than that of the transaminases. ALT turned out to be an earlier biomarker of liver injury than the other two enzymes. No significant association was found between gene polymorphisms and liver enzyme levels, save for GSTP1 Ile/Val + Val/Val and ALT, which points to this genotype as a risk factor for drug-induced liver injury. Future studies might help to identify the underlying mechanisms of transient liver enzyme increase associated with this genotype.

Effects of COVID-19 Infection on the Oral Glucose Tolerance Test Results in Pregnancy.

INTRODUCTION: The aim of this study was to evaluate the results of a 75 g oral glucose tolerance test (OGTT) performed in the second trimester of pregnancy, the prevalence of gestational diabetes mellitus (GDM), and perinatal outcomes in pregnant women with a history of coronavirus disease 2019 (COVID-19) infection and to examine the effect of COVID-19 infection history on OGTT results and GDM prevalence. METHODS: We retrospectively analyzed the data of 463 patients who visited the Gynecology and Obstetrics Department of Kayseri City Hospital between March 2020 and January 2023 and were administered a 75-g OGTT in the second trimester of their pregnancy. Accordingly, we traced COVID-19 history, OGTT results, GDM prevalence, and newborn outcomes among the patients. RESULTS: OGTT glucose values were higher in the study group with a history of COVID-19 infection, but there was no significant difference between the groups. GDM developed in 13 (23.2%) pregnant women in the group with a history of COVID-19 infection and 88 (21.6%) pregnant women in the control group without a history of COVID-19 (p: 0.348). In addition, in pregnant women diagnosed with GDM, insulin requirement was 8.9% in the COVID-19 (+) group and 5.1% in the COVID-19 (-) group, and the results were not statistically significant (p: 0.178). There was no significant difference in neonatal outcomes between the groups. CONCLUSIONS: In our study, we found that glucose values were higher and the prevalence of GDM was higher in pregnant women with a history of COVID-19 infection before the OGTT. It is necessary to be more careful about issues such as blood glucose regulation and GDM risk in pregnancy follow-up after infections such as COVID-19, which may have widespread systemic inflammatory effects, and patients should be informed in detail for pregnancy follow-up.

Fetal Diaphragmatic Excursion Is Decreased in Hospitalized Pregnant Women Infected with COVID-19 during the Second and Third Trimesters.

OBJECTIVE: In the present study, we aimed to evaluate coronavirus disease 2019 (COVID-19) infection effects on fetal diaphragm thickness and diaphragmatic excursion, which together show the quality of diaphragmatic contractions. STUDY DESIGN: One hundred and ninety-two pregnant women were included in this prospective case-control study. Patients were divided into four groups according to their COVID-19 infection history in their second or third trimester: hospitalized COVID-19-infected pregnant women group (n = 48), outpatient COVID-19-infected pregnant women group (n = 48), common cold (COVID-19 polymerase chain reaction negative) pregnant women group (n = 48), and noninfected healthy controls (n = 48). The number of patients was determined by power analysis following the pilot study. All participants underwent an ultrasound examination to determine fetal diaphragm parameters at 32 to 37 weeks of gestation. RESULTS: Demographic characteristics were similar among the four groups. The gestational age at ultrasound examination and gestational age at delivery were similar among the groups. Neonatal intensive care unit (NICU) admission rate was significantly higher in the hospitalized COVID-19-infected pregnant women group than the other groups. The fetal diaphragm thickness during inspiration and expiration, and fetal costophrenic angles at inspiration and expiration were similar among the groups. Fetal diaphragmatic excursion was significantly decreased in the hospitalized COVID-19-infected pregnant women group compared with the other groups. CONCLUSION: Our results indicated that moderate maternal COVID-19 infection decreased fetal diaphragmatic excursion, and ultrasonographic evaluation of fetal diaphragmatic excursion before delivery can provide critical information to predict whether infants will require NICU admission. KEY POINTS: · Diaphragm ultrasound as a new technique for characterizing the diaphragm's structure and function.. · Fetal diaphragmatic excursion is decreased in the presence of moderate COVID-19 infection.. · Ultrasonographic evaluation of fetal diaphragmatic excursion provides critical information to predict NICU admission..

Evaluation of Low-Molecular-Weight Heparin Treatment on First- and Second-Trimester Screening Test Results.

Background The serum markers used in first- and second-trimester screening tests can be affected by different causes such as smoking, infertility treatment, and the presence of diabetes mellitus, which should be considered by obstetricians when giving information to patients. Low molecular weight heparin (LMWH) has a critical importance in the prophylaxis of deep vein thrombosis both in the antenatal and postnatal period. The aim of the current study is to investigate the effect of LMWH use on the first- and second-trimester screening results. Methods A retrospective analysis in our outpatient clinic between July 2018 and January 2021 of first- and second-trimester screening test results was conducted to assess the impact of LMWH treatment for patients with thrombophilia who started LMWH after pregnancy was detected were included. Test results were obtained as a multiple of median (MoM) combined with ultrasound measurements, maternal serum markers, and maternal age in addition to the nuchal translucency first-trimester test. Results The pregnancy-associated plasma protein-A (PAPP-A) MoM was lower and alpha-fetoprotein (AFP) and unconjugated estriol (uE3) MoMs were higher in patients treated with LMWH than in the control group (0.78 MoM vs 0.96 MoM; 1.00 MoM vs 0.97 MoM; and 0.89 MoM vs 0.76 MoM, respectively). Human chorionic gonadotropin (HCG) levels did not differ between groups at either time point. Conclusions Treatment of pregnant women with LMWH for thrombophilia may change the MoM values of serum markers for both first- and second-trimester screening tests. Obstetricians should be aware of this when advising screening tests to thrombophilia patients and should consider offering fetal DNA tests for this group instead.

Severe Intrahepatic Cholestasis Pregnancy Is Associated With Maternal Endothelial Dysfunction: A Case-Control Study.

OBJECTIVE: The aim of the present study was to evaluate maternal serum endocan levels, which are markers of vascular pathologies and strongly associated with vascular inflammation and endothelial dysfunction, in pregnancies complicated by intrahepatic cholestasis of pregnancy (ICP). METHODS: The study comprised 30 pregnant women with mild ICP, 30 pregnant women with severe ICP, and 30 healthy pregnant women as a control group. The inclusion criteria were women with ICP, which was diagnosed based upon the presence of pruritus associated with elevated total bile acid (TBA) levels (> 10 µm/L), elevated aminotransferases, or both, and the absence of diseases that may produce similar laboratory findings and symptoms. Severe ICP was defined as TBA > 40 µmol/L. After diagnosis for ICP, blood samples were obtained before medication during hospitalization to analyze maternal serum endocan levels. RESULTS: Gestational age at delivery, delivery induction rates, birth weight, and newborn intensive care unit (NICU) admission rates were significantly higher in the severe ICP group than in the control group and mild ICP group. Gestational age for all groups when blood was sampled was similar. Maternal serum TBAs and aminotransferase levels were significantly higher in the severe ICP group than in the control group and mild ICP group. The mean serum endocan levels were 10.9 ± 2.6 ng/mL in the control group, 12.5 ± 2.8 ng/mL in the mild ICP group, and 24.3 ± 4.8 ng/mL in the severe ICP group (p < 0.001). CONCLUSION: Our results indicated that maternal serum endocan levels were increased in the presence of severe ICP and it can be speculated that increased bile acid levels were associated with maternal endothelial dysfunction.

Evaluation of Altmetric Analysis Scores of the Top 100 Articles on Polycystic Ovary Syndrome Published in the Last 10 Years.

OBJECTIVE: In the current study, we analyzed the 100 most cited articles with the topic, title, and keywords of polycystic ovary syndrome (PCOS) published in all journals in terms of traditional metrics and the altmetric score (AS). METHODS: The term "polycystic ovary syndrome (PCOS)" was searched in the Web of Science (WoS) database and filtered for articles published in all journals. Bibliographic data and AS were obtained for 100 highly cited papers from January 2012 to July 2022. Descriptive statistics were reported and correlation analysis between traditional bibliographies and the AS was performed. RESULTS: The Journal of Clinical Endocrinology & Metabolism, with 14 articles, had the most publications on the Top 100 list. When the studies were classified according to subtypes, 56 papers were original scientific papers with mean AS of 32.5 (15.3-52.7), whereas 44 papers were reviews and meta-analyses with AS of 16.0 (8.6-43.2). The AS was positively correlated with H-index, total WoS citation number of article and Q category. There were no correlations with impact factor (IF), five-year IF, journal impact factor (JIF) percentile and journal citation indicator (JCI) value. CONCLUSION: Our results suggest that the AS is related with article total WoS citation number, journal Q category, and journal H-index. Effective communication on social media can promote scientific productivity and have a positive impact on society.

Metabolomics mapping changed after olanzapine therapy in drug-naive schizophrenia patients-the significant impact of gene polymorphisms.

Oxidative stress may contribute to the development of schizophrenia and antipsychotics used in schizophrenia treatment may also cause oxidative stress. Gene polymorphisms on antioxidant and repair enzymes are responsible for individual variations and may change the efficacy of olanzapine treatment among schizophrenia patients. In our study, we assessed oxidative stress-related metabolite changes due to genetic polymorphisms on first diagnosed-schizophrenia patients treated with olanzapine. Blood samples (n = 30 patients) were taken before treatment (T1), after 10 ± 1 days (T2), and after 3 ± 1 months (T3). T1 served as control for T2 and T3, since it is advantageous to perform on same patient to evaluate the impact of olanzapine only. GSTs (GSTM1, GSTT1, and GSTP1) and OGG1 gene polymorphisms were analyzed by polymerase chain reaction. Changes in metabolites were detected with metabolomics profiling by gas chromatography-mass spectrometry according to each genotype before and after treatment. Multivariate analysis showed that metabolomics profiles differed after olanzapine treatment regardless gene polymorphisms. Tryptophan could be a biomarker in response to olanzapine treatment since its levels were increased after treatment. GSTM1 gene polymorphism caused significant changes in some metabolites after treatment. Urea, palmitic acid, and caprylic acid levels increased and alanine levels decreased in patients with GSTM1 null genotypes after olanzapine. In future, targeted metabolomics with these prominent metabolites and assessing gene expressions of GSTs will be beneficial to understand the mechanism of action.

Exercise and outcomes in macrosomic pregnancies.

OBJECTIVE: Pregnancy is generally known to be a period when physical activity is partially or totally restricted to avoid negative outcomes such as miscarriage or premature birth. The aim of this study was to evaluate the effect on maternal and fetal outcomes of exercise in pregnancies complicated by macrosomia. MATERIAL AND METHOD: In this retrospective study, the data were retrospectively screened of women who gave birth at ≥38 weeks with infant birthweight of ≥4000 gr. The patients were separated into two groups as those who followed an exercise program of walking regularly for 30-60 mins at least 1 day a week throughout pregnancy and those who did not. The maternal and fetal complications were compared between the groups. A total of 252 patients were included in the study as 84 women who exercised during pregnancy and 168 women selected at random in the ratio of 2:1 who did not exercise. RESULTS: When the gestational week at birth was examined, a statistically significantly higher rate of patients in the non-exercise group gave birth at ≥40 gestational weeks. Although not at a statistically significant level, maternal and fetal complications were observed more in the non-exercise group. CONCLUSIONS: The results of this study showed that excessive maternal weight gain was statistically significantly reduced, and although not at a statistically significant level, maternal and fetal trauma were reduced in macrosomic pregnancies with regular exercise. As recommended by ACOG, for pregnant women at risk of macrosomic fetus, exercise of walking for 30-60 mins several days a week will have positive effects on both the mother and infant.

Cognitive-behavioral therapy in pregnant women with generalized anxiety disorder: a retrospective cohort study on therapeutic efficacy, gestational age and birth weight

Objective: To evaluate the efficacy of cognitive behavioral therapy in the treatment of generalized anxiety disorder during pregnancy and its effects on gestational age and birth weight. Methods: The sample included 28 untreated patients and 23 patients treated with CBT. Psychiatric diagnoses were determined through the Structured Clinical Interview for the DSM-IV. Symptom severity was assessed with standardized rating scales. Results: Post-treatment levels of anxiety symptoms were significantly lower than baseline. There was no significant difference in gestational age or newborn birth weight between the cognitive behavioral therapy group and the untreated group. Conclusions: Cognitive behavioral therapy appears to be a safe and effective treatment for generalized anxiety disorder during pregnancy.

Cognitive-behavioral therapy in pregnant women with generalized anxiety disorder: a retrospective cohort study on therapeutic efficacy, gestational age and birth weight.

OBJECTIVE: To evaluate the efficacy of cognitive behavioral therapy in the treatment of generalized anxiety disorder during pregnancy and its effects on gestational age and birth weight. METHODS: The sample included 28 untreated patients and 23 patients treated with CBT. Psychiatric diagnoses were determined through the Structured Clinical Interview for the DSM-IV. Symptom severity was assessed with standardized rating scales. RESULTS: Post-treatment levels of anxiety symptoms were significantly lower than baseline. There was no significant difference in gestational age or newborn birth weight between the cognitive behavioral therapy group and the untreated group. CONCLUSIONS: Cognitive behavioral therapy appears to be a safe and effective treatment for generalized anxiety disorder during pregnancy.

Factors preventing materno-fetal transmission of SARS-CoV-2.

Although many pregnant women have been infected by coronavirus, the presence of intrauterine vertical transmission has not been conclusively reported yet. What prevents this highly contagious virus from reaching the fetus? Is it only the presence of a strong placental barrier, or is it the natural absence of the some receptor that the viruses use for transmission? We, therefore, need to comprehensively understand the mechanism of action of the mammalian epithelial barriers located in two different organs with functional similarity. The barriers selected as potential targets by SARS-CoV-2 are the alveolo-capillary barrier (ACB), and the syncytio-capillary barrier (SCB). Caveolae are omega-shaped structures located on the cell membrane. They consist of caveolin-1 protein (Cav-1) and are involved in the internalisation of some viruses. By activating leukocytes and nuclear factor-κB, Cav-1 initiates inflammatory reactions. The presence of more than one Cav-1 binding sites on coronavirus is an important finding supporting the possible relationship between SARS-CoV-2-mediated lung injury. While the ACB cells express Cav-1 there is no caveolin expression in syncytiotrophoblasts. In this short review, we will try to explain our hypothesis that the lack of caveolin expression in the SCB is one of the most important physiological mechanisms that prevents vertical transmission of SARS-CoV-2. Since the physiological Cav-1 deficiency appears to prevent acute cell damage treatment algorithms could potentially be developed to block this pathway in the non-pregnant population affected by SARS-CoV-2.

Intra-ovarian stem cell transplantation in management of premature ovarian insufficiency: towards the induced Oogonial Stem Cell (iOSC).

The specialized resident-stem cells in gonads are tasked with restorating damaged ovarian cells following injury to maintain sequential reproductive events. When we talk about premature ovarian insufficiency (POI) we accept the existence of decreased stem cell and their regenerative abilities. The present study was to explain how restorating damaged ovarian cells following injury to maintain sequential reproductive events in evidence-based medicine indexed in PubMed and Web of Science. The exact mechanism is unclear stem cells transfer may improve compromised ovarian function and fertility outcome in women with POI. Soluble factors secreted by stem cell may rescue impaired mitochondrial function in oogonial stem cells, enhance metabolic capacity of resident stem cells, induce local neovascularization in the ovary, and activate gene shifting between transferred stem cells and germ cell precursors. This review may provide insight into how stem cells show some of their beneficial effects on compromised ovarian microenvironment and germ cell niche and paves the way for clinical trials for improving ovarian function of women with POI. We also had the opportunity to share our hypothesis about the design and development of induced oogonial stem cell (iOSC) and its use in POI.

Neutrophil-to-Lymphocyte Ratio and Platelet-to-Lymphocyte Ratio in Discriminating Precancerous Pathologies from Cervical Cancer.

PURPOSE: We aimed to determine the predictive value of several hematological markers of inflammation on the presence/absence of cervical cancer and also to determine their ability in discriminating precancerous cervical pathologies from cervical cancer. MATERIALS AND METHODS: In this study, patients who presented to Acibadem Kayseri Hospital between May 2010 and June 2018 were evaluated. Forty patients with low-grade squamous intraepithelial lesions (LSIL), 40 patients with high-grade squamous intraepithelial lesions (HSIL), and 30 patients with cervical cancer (CC) were retrospectively included in this study. A control group of 70 healthy volunteers with normal cervical cytology was also included in the study. RESULTS: The neutrophil-to-lymphocyte ratio (NLR) was significantly higher in patients with CC than in controls. The platelet-to-lymphocyte ratio (PLR) was significantly higher in patients with CC compared to those with LSIL and HSIL diagnoses and also controls (p < 0.001). Logistic regression analysis revealed that age (OR: 1.075, 95% CI: 1.020-1.132, p=0.007), NLR (OR: 1.643, 95% CI: 1.009-3.142, p=0.047), and PLR (OR: 1.032, 95% CI: 1.003-1.062, p=0.029) were predictors for the presence of CC. ROC curve analysis revealed that both NLR and PLR were predictive of CC with a cutoff value of 2.02 for NLR (71% sensitivity and 60% specificity, AUC: 0.682, p=0.004) and 126.7 for PLR (83% sensitivity and 69% specificity, AUC: 0.752, p < 0.001). CONCLUSION: In addition to patients' age, determination of NLR and PLR values, which are simple, inexpensive, and readily available markers of systemic inflammation, may help in decision making precancerous pathologies of the cervix.

Pharmacological prophylaxis of postpartum exacerbation in depressive and anxiety symptoms: a retrospective study.

The aim of this study was to investigate the efficacy of prophylactic treatment with antidepressants for the prevention of postpartum exacerbation in depressive or anxiety symptoms. The study included data on 33 patients who were followed from pregnancy to the postpartum period at the Department of Psychiatry of a university Hospital. Psychiatric diagnoses were determined by means of a structured clinical interview. The severity of depressive and anxiety symptoms were assessed by means of Hamilton Rating Scale for Depression (HAM-D) and Hamilton Rating Scale for Anxiety (HAM-A), respectively. Prophylactic treatment was initiated within the first 3 days after the delivery. The patients were assessed again with HAM-D and HAM-A at 4-week postpartum. Postpartum prophylaxis was carried out with administration of sertraline at 50 mg/day (n = 7, 21.2%), paroxetine at 20 mg/day (n = 24, 72.7%), and escitalopram at 10 mg/day (n = 2, 6.1%). Statistical analyses indicated that the mean HAM-D and HAM-A scores before (9.45 ± 7.01 and 10.09 ± 6.42, respectively) and after (9.09 ± 6.65 and 9.54 ± 5.97, respectively) the delivery were not significant. Results of the present study suggest that prophylactic use of antidepressants following parturition may be useful in the prevention of postpartum exacerbation of symptoms in women with depression or anxiety disorders.

Infectious complications in morbidly adherent placenta treated with leaving placenta in situ: a cohort series and suggested approach.

Background: The aim of this study is to assess the clinical and microbiological features of infections in patients with morbidly adherent placenta (MAP) treated by leaving placenta in situ (LPIS). Materials and methods: Retrospective analysis of MAP cases who were treated by LPIS between 2 May 2010 and 15 March 2017. The inclusion criteria were gestational age at or above 24 weeks, prenatal diagnosis, elective operation, and complete data. Results: Nineteen MAP cases were treated by LPIS during the study period. The mean ± SD duration for total placental resorbtion was 145 ± 47 days. Three patients were readmitted to the hospital because of fever (3/19). A total of 65 culture samples were taken from the patients during their follow- up periods. In four cases (4/12) cervical cultures showed positive growth [Escherichia coli (2), Klebsiella pneumoniae (1), mixed culture with Enterococcus spp. and E. coli (1)]. Fifteen (15/26) urine samples were sterile, three were polymicrobial. In eight cases, urine culture revealed E. coli growth (one E. coli and Enterococcus spp.). Three out of 16 (3/16) surgical incision samples revealed growth of E. coli. No bacterial growth was detected in blood cultures. Susceptibility results of Gram-negatives indicate that the resistance rates of beta-lactam antibiotics are high (14/20, 70%). No secondary surgical intervention occurred during the study period due to infection. Conclusions: Majority of postpartum cervical discharge, fever, and increased CRP levels do not represent morbid infections and/or sepsis. With early detection, and implementation of antibiotherapy (combination of an aminoglycoside and clindamycin), they can be easily controlled and secondary surgical interventions can be prevented.

Leaving the placenta in situ versus conservative and radical surgery in the treatment of placenta accreta spectrum disorders.

OBJECTIVE: To compare different treatment methods in the management of placenta accreta spectrum (PAS) disorders. METHODS: In a retrospective cohort study, medical records were retrieved for patients who underwent elective surgery at 24 weeks of pregnancy or more after a diagnosis of PAS disorder (creta, increta, or percreta) at a center in Turkey between May 2, 2010, and August 10, 2016. The final analysis included patients whose diagnosis was confirmed intraoperatively and for whom complete data were available. Patients were divided into three groups: group 1 included those who underwent hysterectomy without placental removal, group 2 included patients whose placenta was left in situ, and group 3 included those who underwent placental removal and conservative surgery. RESULTS: Among 79 included patients (33 creta, 18 increta, 28 percreta), 27 (34%) were in group 1, 15 (19%) in group 2, and 37 (47%) in group 3. Total blood loss and the amounts of blood products transfused were lowest in group 2; significant differences between groups were noted (all P ≤ 0.001). Surgical complication rates were similar between groups (4/27 [15%], 1/15 [7%], and 11/37 [30%], respectively; P=0.119). Overall uterine preservation rates were not significantly different between groups 2 and 3 (14/15 [93%] vs 33/37 [89%]; P>0.99). CONCLUSION: Leaving the placenta in situ could become the treatment of choice for PAS disorders.

Comparison of systemic and local methotrexate treatments in cesarean scar pregnancies: time to change conventional treatment and follow-up protocols.

OBJECTIVE: The aim of this study was to compare the use of systemic and local methotrexate in the treatment of cesarean scar pregnancy. STUDY DESIGN: In this retrospective cohort study, we collected the data of 44 patients with cesarean scar pregnancy. The patients were grouped according to treatment modality: Group 1, local methotrexate injection (n=17) and Group 2, systemic methotrexate (n=27). The groups were compared with respect to side effects, recovery time, reproductive outcome, and treatment cost. RESULTS: The mean gestational age at diagnosis (6.4±0.93 vs. 5.4±0.80 weeks, p=0.001), pretreatment serum ß-human chorionic gonadotrophin level [27,970 (11,010-39,421) vs. 7606 (4725-16,996) mIU/mL, p=0.001], and lesion size (2.74±1.36 and 1.28±0.55cm, p=0.001) were higher in Group 1. All patients were cured by primary therapy without additional surgery. The mean times for ß-human chorionic gonadotrophin normalization, the uterine-mass disappearance, were significantly shorter in Group 1 than in Group 2 (6.17±1.55 vs. 8.11±2.0 weeks, p=0.001 and 10.47±4.14 vs. 13.40±4.44 weeks, p=0.002, respectively). The cost of treatment was similar between groups (281.133±112.123$ vs. 551.134±131.792$, p=0.76). The total pregnancy rates were not different between groups (5/16, 31.4% vs. 6/11, 54.6%, p=0.301). One recurrent cesarean scar pregnancy occurred after systemic methotrexate. Oral ulcers, the most common side effect, were seen in seven patients in Group 2. CONCLUSION: Even though treatment success and reproductive outcomes are similar, local methotrexate is superior to systemic methotrexate with regard to recovery time, side effects, and treatment costs, even in patients with unfavorable pretreatment prognostic predictors.