Liver damage profile in COVID-19 pregnant patients.

INTRODUCTION: SARS-CoV-2 unsparingly impacts all areas of medicine. Pregnant women are particularly affected by the pandemic and COVID-19 related liver damage seems to be another threat to maternal and fetal health. The aim of this study is to define liver damage profile including bile acids serum levels in COVID-19 pregnant patients and to determine predictors of disease aggravation and poor obstetrics outcomes. METHODS: This study has been carried out in the Obstetrics and Gynecology Department, at the National Medical Institute in Warsaw, Poland between 01.02.2021 and 01.11.2022 The study cohort comprises 148 pregnant patients with COVID-19 and 102 pregnant controls who has been tested negative for SARS-CoV-2. RESULTS: COVID-19 pregnant patients presented liver involvement at admission in 41,9%. Hepatotoxic damage accounted for 27 (19.85%), cholestatic type was diagnosed in 11 (8.09%) and mixed type of liver injury was presented in 19 (13.97%) of patients. Higher serum levels of AST, ALT, GGT, total bilirubin and bile acids as well as mixed type of liver injury at admission were correlated with severe form of an illness. AST and ALT above upper reference limit as well as hepatotoxic type of liver damage predisposed pregnant patients with COVID-19 to poor obstetrics outcomes. CONCLUSION: Hepatic damage in pregnant women with COVID-19 is a common, mild, transaminase-dominant, or mixed type of injury, and often correlates with elevated inflammatory markers. SARS-CoV-2 test should be performed as a part of differential diagnosis in elevated liver function tests. Although bile acids serum levels were commonly elevated they seems to be clinically irrelevant in terms of pregnancy outcomes. Video Abstract.

Central nervous system disorders after use of dolutegravir: evidence from preclinical and clinical studies.

The evaluation of dolutegravir based on available preclinical and clinical studies reveals a risk of central nervous system (CNS) disorders associated with long-term use of the drug. The available literature on the pharmacokinetics of the drug, including its penetration of the blood-brain barrier, was reviewed, as well as clinical trials assessing the incidence of adverse effects in the CNS and the frequency of its discontinuation. This paper also summarizes the impact of factors affecting the occurrence of CNS disorders and indicates the key role of pharmacovigilance in the process of supplementing knowledge on the safety of drugs, especially those that are newly registered.

Assessment of the birth status of children born by elective caesarean section before and after 39 weeks of gestation following in vitro fertilization.

The collected material presents 512 mothers with children whose pregnancies were ended by caesarean section at the Department of Obstetrics, Women's Diseases and Oncological Gynecology Central Clinical Hospital of the Ministry of Internal Affairs in Warsaw in the years 2004-2016. The study group consisted of 362 mothers in pregnancies following in vitro fertilization and 150 mothers in spontaneous pregnancy, without the use of assisted reproductive technology. For the purposes of the project, only single pregnancies ending within weeks 37 to 41 of pregnancy were selected. Planned delivery by elective cesarean section (ECS) currently takes place after the 39th week of pregnancy, in line with current common recommendations. This is related to studies finding an overall better birth condition of newborns in the general population, and especially regarding the maturation of the lungs. Currently, there are no specific recommendations regarding cesarean section and the timing of delivery in pregnancies resulting from in vitro fertilization. The aim of this study was to assess the optimal time of an elective cesarean section at full term in an IVF pregnancy. Consistent with findings in the general population and prevailing recommendations, the expected result would be the better condition of the baby born by ECS following the 39th week of gestation. However, our statistical analysis of the collected material shows that the group delivered by ECS prior to the end of 39 weeks of pregnancy may have fewer respiratory system interventions and higher Apgar scores. Nevertheless, results lack statistical significance. In conclusion these findings may indicate a need for a bigger database.

Long-term Administration of 3-Di-O-Tolylguanidine Modulates Spatial Learning and Memory in Rats and Causes Transition in the Concentration of Neurotransmitters in the Hippocampus, Prefrontal Cortex and Striatum.

The sigma-1 and sigma-2 (σ1 and σ2) receptors are found in high concentrations in the brain, and their altered expression leads to a variety of neuropsychiatric disorders. 3-di-tolylguanidine (DTG) stimulates the activity of both of these receptors. We assessed the effects of administering DTG to adult male Sprague Dawley rats on learning and memory consolidation processes and on the levels of neurotransmitters in selected brain structures. Spatial learning and memory were evaluated in the water maze test. The DTG was administered orally at daily doses of 3 mg/kg (DTG3), 10 mg/kg (DTG10) or 30 mg/kg (DTG30) for 10 weeks before and during the water-maze test. After completion of the experiment, the concentration of monoamines and their metabolites as well as amino acids in structures involved in cognitive performance - the hippocampus, prefrontal cortex, and striatum - were determined using high performance liquid chromatography (HPLC). The DTG10 group showed an improvement in memory processes related to the "new" platform location, whereas the DTG30 group was worse at finding the "old" platform location. Since the administration of DTG led to differences in dopaminergic transmission, it was assumed to influence memory processes in this way. Changes in histidine, serine, alanine, taurine, and glutamic acid levels in selected structures of the brains of rats with memory impairment were also observed. We conclude that long-term administration of DTG modulates spatial learning and memory in rats and changes the concentrations of neurotransmitters in the hippocampus, prefrontal cortex, and striatum..

Postpartum Blood Loss in COVID-19 Patients-Propensity Score Matched Analysis.

The aim of this study was to compare the estimated blood loss and the frequency of obstetric hemorrhage among pregnant women with and without COVID-19 infection. The study was carried out in the Department of Obstetrics and Gynecology, at the Central Clinical Hospital of the Ministry of the Interior and Administration in Warsaw, Poland. From 15 May 2020 to 26 April 2021, a total of 224 parturients with COVID-19 infection were admitted for labor. The control group consisted of 300 randomly recruited pre-pandemic deliveries that took place between 15 May 2019 and 26 April 2020 at the Department. The primary outcome was the presence of postpartum hemorrhage, defined as an estimated blood loss of ≥500 mL within 24 h after birth or the need to transfuse 2 or more units of packed red blood cells (pRBCs). Secondary outcomes were the difference between hemoglobin and hematocrit levels at 24 h postpartum, the number of pRBCs units transfused, and the need for transperitoneal drainage. After applying the propensity-score-matching procedure for postpartum bleeding risk factors, 325 eligible patients were included in the final analysis, divided into 203 COVID-19 positive and 122 COVID-19 negative prepandemic deliveries. SARS-CoV-2 infected patients were characterized by a longer activated partial thromboplastin time (APTT), a reduced prothrombin time (PT), and lower platelet count at initial presentation. COVID-19 deliveries were found to be associated with a higher frequency of postpartum hemorrhage, an increased estimated blood loss, the more frequent use of peritoneal drainage, and more pRBCs units transfused. During the pandemic, an increased risk of postpartum hemorrhage posed another threat to SARS-CoV-2 infected pregnant women. It is essential to be aware of this when approaching COVID-19 delivery and to implement efficient preventative methods.

COVID-19 Severity and Mortality in Two Pandemic Waves in Poland and Predictors of Poor Outcomes of SARS-CoV-2 Infection in Hospitalized Young Adults.

SARS-CoV-2 variants pose a significant threat to global public health. However, their influence on disease severity, especially among young adults who may exhibit different clinical characteristics, is debatable. In this retrospective study of 229 young adults hospitalized with COVID-19, we investigated the differences between Poland's second and third waves of the pandemic. To identify potential predictors of severe COVID-19 in young adults, we analyzed patient characteristics and laboratory findings between survivors and non-survivors and we performed logistic regression to assess the risk of death, mechanical ventilation, and intensive care unit treatment. We found no increase in COVID-19 severity comparing the third and second waves of the pandemic, indicating that the alpha variant had no influence on disease severity. In addition, we found that factors, such as obesity, comorbidities, lung involvement, leukocytosis, neutrophilia, lymphopenia, higher IG count, the neutrophil-to-lymphocyte ratio, C-reactive protein, procalcitonin, interleukin-6, D-Dimer, lactate dehydrogenase, high-sensitive troponin I, creatine kinase-myocardial band, myoglobin, N-terminal-pro-B-type natriuretic peptide, creatinine, urea and gamma-glutamyl transferase, lower estimated glomerular filtration rate, albumin, calcium and vitamin D3, possibly a decrease in red blood cell counts, hemoglobin and hematocrit, and an increase in creatine kinase during hospitalization may be associated with poor outcomes of COVID-19.

Predictors of COVID-19 severity among pregnant patients.

Coronavirus disease 2019 (COVID-19) was declared a pandemic and has spread around the globe, unsparingly affecting vulnerable populations. Effective prevention measures for pregnant women, who are particularly affected, include early identification of those patients at risk of developing in-hospital complications, and the continuous improvement of maternal-fetal treatment strategies to ensure the efficient use of health resources. The objective of our retrospective study was to determine which patient biomarkers on hospital admission correlate with disease severity as measured by disease course classification, the need for oxygen supplementation and higher demand for oxygen, the need for mechanical ventilation, intensive care unit admission, and length of hospital stay. Analysis of 52 PCR SARS-CoV-2 positive pregnant women revealed that the median date of hospital admission was the 30th gestational week, with dyspnoea, cough, and fever as the leading symptoms. The presence of diabetes and hypertension predisposed pregnant women to the severe course of illness. Lung involvement shown by CT scans on admission correlated with the greater clinical severity. The main laboratory predictors of disease progression were lymphocytopenia, hypocalcemia, low total cholesterol, low total protein levels, and high serum levels of C-reactive protein, ferritin, interleukin-6, glucose, lactate dehydrogenase, procalcitonin, and troponin I. Further research with a larger cohort of pregnant women is needed to determine the utility of these results for everyday practice.

Is the Course of COVID-19 Different during Pregnancy? A Retrospective Comparative Study.

The COVID-19 pandemic has challenged health systems around the world. Maternal-foetal medicine, which has been particularly affected, must consider scientific data on the physiological processes occurring in the pregnant woman's body to develop relevant standards of care. Our study retrospectively compared the clinical and laboratory characteristics of 52 COVID-19 pregnant patients with 53 controls. Most of the pregnant patients required medical attention during the third trimester and therefore we propose that vaccination is needed prior to the 30th week of pregnancy. We found no differences between the 2 groups in the course of illness classification system, days of hospital stay, need for oxygen supplementation, need for mechanical ventilation, and ICU admission. Moreover, clinical manifestations and imaging findings were comparable. Pregnant patients needed a greater oxygen flow rate and required high flow oxygen therapy more frequently. Considering pregnancy-related physiological adaptations, we found that COVID-19 infection in pregnant patients is associated with higher levels of inflammatory markers, apart from serum ferritin, than in non-pregnant women, and concluded that biomarkers of cardiac and muscle injury, as well as kidney function, may not be good predictors of COVID-19 clinical course in pregnant patients at the time of admission, but more research needs to be conducted on this topic.

Sigma receptors and neurological disorders.

ABSTARCT: Sigma receptors were identified relatively recently, and their presence has been confirmed in the central nervous system and peripheral organs. Changes in sigma receptor function or expression may be involved in neurological diseases, and thus sigma receptors represent a potential target for treating central nervous system disorders. Many substances that are ligands for sigma receptors are widely used in therapies for neurological disorders. In the present review, we discuss the roles of sigma receptors, especially in the central nervous system disorders, and related therapies.

COVID-19 in Pregnancy-Perinatal Outcomes and Vertical Transmission Preventative Strategies, When Considering More Transmissible SARS-CoV-2 Variants.

The COVID-19 pandemic affected the physical and mental health of people around the world and left unprepared health care systems struggling to mount an adequate response. Understanding the impact of COVID-19 on pregnancy in terms of perinatal and fetal outcomes is essential to propose strategies for mminimising viral transmission. Overall, 91 pregnant women in labour, or with indication for induction of labour, with COVID-19 were admitted to hospital. On the day of admission, each pregnant woman underwent a nasopharyngeal swab to validate SARS-CoV-2 infection. Whenever delivery was by caesarean section, an amniotic fluid sample was collected after uterus incision. Neonates were tested twice: first by nasopharyngeal swab at birth and secondly either at 24 h after (when babies were isolated) or at discharge (when rooming-in). All samples underwent rRT-PCR testing for SARS-CoV-2. The SARS-CoV-2 RNA tests by nasopharyngeal swab of the pregnant women produced positive results in 47 patients. This cohort gave birth to 48 infants who were double tested by nasopharyngeal swab and included in the prospective observational study. Moreover, in this same cohort, 39 amniotic fluid samples were taken during caesarean section. All samples underwent rRT-PCR testing for SARS-CoV-2 and came back negative. The study results suggest a low risk of vertical transmission of COVID-19 and favourable perinatal outcomes due to adequate preventative strategies. This approach may prove to be more beneficial in the new SARS-CoV-2 variants era.

Absence of SARS-CoV-2 RNA in Peritoneal Fluid During Surgery in Pregnant Women Who Are COVID-19 Positive.

STUDY OBJECTIVE: Coronavirus disease 2019 (COVID-19) infection poses significant risks during surgical interventions. We investigated the intraperitoneal presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in patients who are COVID-19 positive. DESIGN: A prospective group study. SETTING: Department of Obstetrics and Gynecology designated for patients with COVID-19, Central Clinical Hospital of the Ministry of Interior, Warsaw. PATIENTS: Overall, 65 pregnant women with COVID-19 infection underwent cesarian section. The diagnosis was confirmed either by positive antigen test or by positive reverse transcriptase-polymerase chain reaction assay performed within no more than 13 days before the operation. INTERVENTIONS: On the day of the operation, a nasopharyngeal swab was taken, and peritoneal fluid was collected at the beginning of the operation. Both the nasopharyngeal swab and peritoneal fluid samples were tested for SARS-CoV-2. MEASUREMENTS AND MAIN RESULTS: A total of 65 pregnant women with COVID-19 infection were enrolled in the study. The SARS-CoV-2 ribonucleic acid test by nasopharyngeal swab produced positive results in 34 patients. In this group as well as in 31 nonconfirmed patients, all peritoneal fluid samples tested negative for SARS-CoV-2 ribonucleic acid. CONCLUSION: These results suggest a low risk of COVID-19 transmission from the peritoneal cavity at the time of laparoscopy or laparotomy.

Metabolic and hormonal effects of a combined Myo-inositol and d-chiro-inositol therapy on patients with polycystic ovary syndrome (PCOS).

OBJECTIVES: To evaluate the effects of a combined Myo-inositol (MI) and D-chiro-inositol (DCI) therapy on the hormonal and metabolic parameters of women with PCOS. Prospective clinical study. Clinical Study registration number - EUPAS25705 Material and methods: Seventy women diagnosed with PCOS according to the Rotterdam criteria were enrolled in this study. Patients received a combined therapy of one tablet that contained 550 mg of inositol (myo-inositol (MI) and D-chiro-inositol (DCI) in a ratio of 10:1) twice a day for 6 months. At each of 3 visits, the body weight, height and BMI were all recorded; and serum levels of free testosterone (fT), sex hormone-binding globulin (SHBG), luteinizing hormone (LH), follicle-stimulating hormone (FSH) and glucose with insulin during standard OGTT (75 g) were measured. Also at each visit, transvaginal ultrasonography and skin condition assessments were performed. RESULTS: Significant body weight reduction and decreases in fT, FSH, LH and insulin levels, as well as significant increase of serum SHBG concentrations were observed. Serum glucose levels during OGTT decreased after 6 months of treatment. Also, skin conditions improved after only three months of treatment. CONCLUSIONS: Combination of MI and DCI in a ratio 10:1 seems to be efficient in improving both metabolic and hormonal parameters in patients with PCOS.

Presurgical diagnostic difficulties in an asymptomatic patient with primary transitional cell carcinoma of the oviduct: case report.

Primary transitional cell carcinoma of the fallopian tube is a very rare condition. We present a case of a 70-year-old asymptomatic Caucasian patient with an irregular solid right adnexal mass of 67 × 35 × 59 mm which was discovered during routine ultrasound pelvic examination. There was no acoustic shadow and the patient did not feel pain during examination. No evidence of metastases or ascites was found by ultrasound. There was moderate vascularization of the mass. The mass was considered malignant according to the subjective assessment of the examiner. Serum level of CA125 was elevated to 519 U/ml. The results of logistic regression model LR2 according to the International Ovarian Tumor Analysis (IOTA) group was 64.4%, suggesting the malignant nature of the mass. The IOTA-ADNEX model showed 97% probability of malignancy, probably (85.5%) stage II-IV ovarian cancer. The risk of malignancy being borderline, stage I and metastatic was 0.6%, 3.9% and 7%, respectively. Omitting CA125 in the IOTA-ADNEX model slightly decreased the probability of malignancy to 81.3%, still most likely (54.2%) stage II-IV ovarian cancer. The results of risk of malignancy indices RMI I-IV were 1557, 2076, 1557 and 2076, respectively, reflecting the malignant nature of the mass. The final diagnosis was transitional cell carcinoma of the fallopian tube, stage IIIc according to FIGO.