Clinical, Laboratory, and Imaging Findings of Pregnant Women with Possible Vertical Transmission of SARS-CoV-2-Case Series.

The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic significantly impacted the general population's health. At times, the infection has unfavorably influenced pregnancy evolution and the result of birth. However, vertical transmission of the virus is rare and generates controversial discussions. The study aimed to highlight the clinical, laboratory, and imaging findings of pregnant women with confirmed Coronavirus Disease 2019 (COVID-19) with possible vertical transmission and identify possible factors that encourage vertical transmission. Between 1 April 2020 and 31 December 2021, 281 pregnant women diagnosed with COVID-19 gave birth in the Obstetrics and Gynecology Departments of the tertiary unit of County Emergency Clinical Hospital from Timisoara. Three newborns (1.06%) tested positive. The characteristic of these three cases was described as a short series. In two cases, the patients were asymptomatic. In one case, the patient developed a mild form of COVID-19 with a favorable evolution in all cases. We did not identify the presence of smoking history, vaccine before admission, atypical presentation, fever, or chest X-ray abnormalities. We note possible factors that encourage vertical transmission: Pregnancy-induced hypertension, thrombophilia, asymptomatic cough, an asymptomatic or mild form of the disease, a ruptured membrane, and cesarean. The laboratory results highlight the inconstant presence of some changes found in the list of potential predictors of the severity of the infection: Lymphopenia, high values of C-reactive protein, D-dimer, fibrinogen, platelets, Aspartate Aminotransferase, Lactate dehydrogenase, and ferritin. The study's conclusion of this small group suggests that there may have been an intrauterine infection in late pregnancy and described characteristics of the pregnant women. Possible risk factors that could encourage vertical transmission have been identified.

In Vitro Toxicological Profile of Labetalol-Folic Acid/Folate Co-Administration in H9c2(2-1) and HepaRG Cells.

Background and Objectives: The consumption of dietary supplements has increased over the last decades among pregnant women, becoming an efficient resource of micronutrients able to satisfy their nutritional needs during pregnancy. Furthermore, gestational drug administration might be necessary to treat several pregnancy complications such as hypertension. Folic acid (FA) and folate (FT) supplementation is highly recommended by clinicians during pregnancy, especially for preventing neural tube birth defects, while labetalol (LB) is a ß-blocker commonly administered as a safe option for the treatment of pregnancy-related hypertension. Currently, the possible toxicity resulting from the co-administration of FA/FT and LB has not been fully evaluated. In light of these considerations, the current study was aimed at investigating the possible in vitro cardio- and hepato-toxicity of LB-FA and LB-FT associations. Materials and Methods: Five different concentrations of LB, FA, FT, and their combination were used in myoblasts and hepatocytes in order to assess cell viability, cell morphology, and wound regeneration. Results: The results indicate no significant alterations in terms of cell viability and morphology in myoblasts (H9c2(2-1)) and hepatocytes (HepaRG) following a 72-h treatment, apart from a decrease in the percentage of viable H9c2(2-1) cells (~67%) treated with LB 150 nM−FT 50 nM. Additionally, LB (50 and 150 nM)−FA (0.2 nM) exerted an efficient wound regenerating potential in H9c2(2-1) myoblasts (wound healing rates were >80%, compared to the control at 66%), while LB-FT (at all tested concentrations) induced no significant impairment to their migration. Conclusions: Overall, our findings indicate that LB-FA and LB-FT combinations lack cytotoxicity in vitro. Moreover, beneficial effects were noticed on H9c2(2-1) cell viability and migration from LB-FA/FT administration, which should be further explored.

The Impact of SARS-CoV-2 Pandemic on Patients Undergoing Radiation Therapy for Advanced Cervical Cancer at a Romanian Academic Center: A Four-Year Retrospective Analysis.

Background and Objectives: Throughout the COVID-19 pandemic, health systems worldwide adapted to support COVID-19 patients while continuing to provide assistance to patients with other potentially fatal illnesses. While patients with cancer may be at an elevated risk of severe COVID-19-related complications, their oncologic therapies generally cannot be postponed indefinitely without a negative effect on outcomes. Taking this into account, a thorough examination of the therapy management of various cancers is necessary, such as cervical cancer. Therefore, we aimed to develop a retrospective cohort study to measure the impact of the COVID-19 pandemic on the delivery of cancer care services for women diagnosed with cervical cancer staged IB2-IVA, necessitating chemo- and radiotherapy in Romania, as well as determine the difference in cervical cancer staging between the pandemic and pre-pandemic period. Materials and Methods: Using a multicentric hospital database, we designed a retrospective study to compare the last 24 months of the pre-pandemic period to the first 24 months of the SARS-CoV-2 pandemic to evaluate the variation in the proportion of women diagnosed with cervical cancer and the percentage of inoperable cases requiring chemotherapy and radiotherapy, as well as to detail their clinical presentation and other findings. Results: We observed that the likelihood of cervical cancer patients requiring radiation therapy at a later stage than before the pandemic increased by about 20% during the COVID-19 pandemic. Patients at an advanced FIGO stage of cervical cancer had a 3.39 higher likelihood of disease progression after radiotherapy (CI [2.06−4.21], p-value < 0.001), followed by tumor size at diagnosis with a hazard ratio (HR) of 3.12 (CI [2.24−4.00], p-value < 0.001). The factors related to the COVID-19 pandemic, postponed treatment and missed appointments, were also identified as significant risk factors for cervical cancer progression (HR = 2.51 and HR = 2.24, respectively). Conclusions We predict that there will be a considerable rise in cervical cancer cases over the next several years based on existing data and that expanding screening and treatment capacity will attenuate this with a minimal increase in morbidity and fatality.

COVID-19 Pandemic Effects on Cervical Cancer Diagnosis and Management: A Population-Based Study in Romania.

The Pap test plays a significant role worldwide in the early diagnosis of and high curability rates for cervical cancer. However, the coronavirus disease 2019 (COVID-19) pandemic necessitated the use of multiple drastic measures to stop the spread of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus, limiting women's access to essential invasive and non-invasive investigations for cervical cancer diagnosis. Therefore, we aimed to determine the impact the COVID-19 pandemic had on cancer diagnosis and management in western Romania. A retrospective study design allowed us to compare the last 24 months of the pre-pandemic period with the first 24 months of the COVID-19 pandemic to determine the change in volume of cervical screening tests, the number of newly diagnosed cases and their severity, and the access to cancer care. A drastic 75.5% decrease in the volume of tests was observed in April 2020 during the first lockdown, after which the volume of cases decreased by up to 36.1% in December 2021. The total volume loss of tests during the first 24 months of the pandemic was 49.9%. The percentage of late-stage cervical cancers (III-IV) rose by 17%, while the number of newly diagnosed cancers in our outpatient clinic was significantly lower than the baseline, with a 45% drop. The access to cancer care was negatively influenced, with 9.2% more patients waiting longer to receive test results over four weeks, while taking longer to seek cancer care after diagnosis (6.4 months vs. 4.1 months pre-pandemic) and missing significantly more appointments. The COVID-19 pandemic had a significantly negative impact on cervical cancer diagnosis and management during the first 24 months compared with the same period before the pandemic. Although the numbers are now recovering, there is still a big gap, meaning that many cervical cancer cases were potentially missed. We recommend further interventions to reduce the gap between the pre-pandemic and pandemic period.

COVID-19 Pandemic Impact on Surgical Treatment Methods for Early-Stage Cervical Cancer: A Population-Based Study in Romania.

Being one of the most common malignancies in young women, cervical cancer is frequently successfully screened around the world. Early detection enables for an important number of curative options that allow for more than 90% of patients to survive more than three years without cancer relapse. Unfortunately, the COVID-19 pandemic put tremendous pressure on healthcare systems and access to cancer care, determining us to develop a study on the influence the pandemic had on surgical care of cervical cancer, and to assess changes in its management and outcomes. A retrospective study design allowed us to compare cervical cancer trends of the last 48 months of the pre-pandemic period with the first 24 months during the COVID-19 pandemic, using the database from the Timis County Emergency Clinical Hospital. New cases of cervical cancer presented to our clinic in more advanced stages (34.6% cases of FIGO stage III during the pandemic vs. 22.4% before the pandemic, p-value = 0.047). These patients faced significantly more changes in treatment plans, postponed surgeries, and postponed radio-chemotherapy treatment. From the full cohort of cervical cancer patients, 160 were early stages eligible for curative intervention who completed a three-year follow-up period. The disease-free survival and overall survival were not influenced by the surgical treatment of choice, or by the SARS-CoV-2 infection (log-rank p-value = 0.449, respectively log-rank p-value = 0.608). The individual risk factors identified for the three-year mortality risk were independent of the SARS-CoV-2 infection and treatment changes during the COVID-19 pandemic. We observed significantly fewer cases of cervical cancer diagnosed per year during the first 24 months of the COVID-19 pandemic, blaming the changes in healthcare system regulations that failed to offer the same conditions as before the pandemic. Even though we did not observe significant changes in disease-free survival of early-stage cervical cancers, we expect the excess of cases diagnosed in later stages to have lower survival rates, imposing the healthcare systems to consider different strategies for these patients while the pandemic is still ongoing.

Challenges in Diagnosis and Prevention of Iatrogenic Endometriosis as a Long-Term Surgical Complication after C-Section.

Endometriosis is a gynecological condition caused by the development of endometrial tissue outside the uterine cavity. Naturally, it commonly occurs at locations such as the ovaries and pelvic peritoneum. However, ectopic endometrial tissue may be discovered outside of the typical sites, suggesting the possibility of iatrogenic seeding after gynecological operations. Based on this hypothesis, we developed a study aiming to establish the root cause of atypical implantation of endometrial foci, as the main end point, and to determine diagnostic features and risk factors for this condition, as a secondary target. The research followed a retrospective design, including a total of 126 patients with endometriosis who met the inclusion criteria. A group of 71 patients with a history of c-section was compared with a control group of patients with endometriosis and no history of c-section. Endometriosis that developed inside or in close proximity to surgical incisions of asymptomatic patients before surgical intervention was defined as iatrogenic endometriosis. Compared with patients who did not have a c-section, the c-section group had significantly more minimally invasive pelvic procedures and multiple adhesions and endometriosis foci at intraoperative look (52.1% vs. 34.5%, respectively 52.1% vs. 29.1%). The most common location for endometriosis lesions in patients with prior c-section was the abdominal wall (42.2% vs. 5.4%), although the size of foci was significantly smaller by size and weight (32.2 mm vs. 34.8 mm, respectively 48.6 g vs. 53.1 g). The abdominal wall endometriosis was significantly associated with minimally invasive pelvic procedures (correlation coefficient = 0.469, p-value = 0.001) and c-section (correlation coefficient = 0.523, p-value = 0.001). A multivariate regression analysis identified prior c-section as an independent risk factor for abdominal wall endometriosis (OR = 1.85, p-value < 0.001). We advocate for strict protocols to be implemented and followed during c-section and minimally invasive procedures involving the pelvic region to ensure minimum spillage of endometrial cells. Further research should be developed to determine the method of abdominal and surgical site irrigation that can significantly reduce the risk of implantation of viable endometrial cells. Understanding all details of iatrogenic endometriosis will lead to the development of non-invasive disease diagnosis and minimally invasive procedures that have the potential to reduce postoperative complications.

The Influence of Nutritional Supplementation for Iron Deficiency Anemia on Pregnancies Associated with SARS-CoV-2 Infection.

Anemia is a very common occurrence during pregnancy, with important variations during each trimester. Anemia was also considered as a risk factor for severity and negative outcomes in patients with SARS-CoV-2 infection. As the COVID-19 pandemic poses a significant threat for pregnant women in terms of infection risk and access to care, we developed a study to determine the impact of nutritional supplementation for iron deficiency anemia in correlation with the status of SARS-CoV-2 infection. In a case-control design, we identified 446 pregnancies that matched our inclusion criteria from the hospital database. The cases and controls were stratified by SARS-CoV-2 infection history to observe the association between exposure and outcomes in both the mother and the newborn. A total of 95 pregnant women were diagnosed with COVID-19, having a significantly higher proportion of iron deficiency anemia. Low birth weight, prematurity, and lower APGAR scores were statistically more often occurring in the COVID-19 group. Birth weight showed a wide variation by nutritional supplementation during pregnancy. A daily combination of iron and folate was the optimal choice to normalize the weight at birth. The complete blood count and laboratory studies for iron deficiency showed significantly decreased levels in association with SARS-CoV-2 exposure. Puerperal infection, emergency c-section, and small for gestational age were strongly associated with anemia in patients with COVID-19. It is imperative to screen for iron and folate deficiency in pregnancies at risk for complications, and it is recommended to supplement the nutritional intake of these two to promote the normal development and growth of the newborn and avoid multiple complications during pregnancy in the COVID-19 pandemic setting.

The prognostic role of Bcl-2, Ki67, c-MYC and p53 in diffuse large B-cell lymphoma.

Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous group of lymphoid malignancies, which counts for more than a third of non-Hodgkin's lymphoma cases. The aim of the current study is to evaluate the prognostic role of several immunohistochemical (IHC) markers involved in the pathological process of DLBCL. This is a retrospective analysis of the 97 de novo DLBCL patients admitted between January 2007 and December 2016 in the Department of Hematology, "Filantropia" Municipal Hospital, Craiova, Romania. The expression of Bcl-2, Ki67, c-MYC and p53 was assessed by immunohistochemistry. A significant level of association was observed between high prognostic index values and Bcl-2, Ki67, c-MYC and p53 positive cases. Moreover, overall survival and disease-free survival were higher in patients with negative expression for these markers. Bcl-2, Ki67, c-MYC and p53 could make important diagnostic and therapeutic targets; therefore, their routine assessment should be mandatory.

Correlation of clinical and biological evidence - a dominant therapeutic element of succeeding in ectopic pregnancy.

Tubal pathology, smoking, pelvic inflammatory disease, miscarriage, medical or surgical abortion, usage of intrauterine devices (IUDs) for women with salpingitis latent injuries, older than 40 years, are risk factors for ectopic pregnancy. The objective of this study concerns the correlation of the clinical and biological evidence for the early diagnosis of the ectopic pregnancy and, as soon as possible, for the estimation for eventual risk of complications that may appear. The transvaginal ultrasound test, minimal increases in serum beta-human chorionic gonadotropin (ß-hCG) dynamics and blood counts are investigations of choice in achieving our objective. Overcoming ß-hCG critical level (>1198 IU÷mL), the decrease of platelets and changes in platelet constants announce the imminent risk of ectopic pregnancy rupture and the need to take a quick decision on the course of treatment.

Apert syndrome - clinical case.

Apert syndrome - acrocephalosyndactyly - is a rare autosomal dominant disorder representing 1:65 000 cases of living newborns. Characteristic malformations of the Apert syndrome are early craniostenosis, microviscerocranium and II-V finger syndactyly of hand and toes with proximal phalanx of the bilateral thumb "in delta". It is difficult to determine prenatal diagnosis in the second quarter, when examining the morphology of fetal signs; the dysmorphism signs appeared in the third pregnancy quarter. We present here the case of a newborn with Apert syndrome that was born prematurely in our Clinic after a monitored pregnancy, where there was issued a suspicion of cranio-facial dysmorphism, malposition and malformation of the feet and hands in the third quarter of prenatal pregnancy. The diagnosis of Apert syndrome was placed on clinical signs, laboratory and genetic tests. The clinical outcome of the baby in the maternity was favorable, the therapeutic management being established by a multidisciplinary team. Immediate complications were due to the case of prematurity: respiratory distress syndrome and the characteristics of the syndrome: micrognathia and naso-facial dysmorphism, syndactyly, bilateral foot metatarsus adductus.

Explants-isolated human placenta and umbilical cord cells share characteristics of both epithelial and mesenchymal stem cells.

In recent years, identification of new sources of adult stem cells developed rapidly, pursuing to find easily available tissues, which will give rise to homogenous stem cells populations. Up to present, bone marrow-derived mesenchymal stem cells (BM-MSCs) are unanimously considered to fulfill the criteria for being used in clinical settings, but adipose stem cells, placental and umbilical cord stem cells, and other tissue-derived stem cells are making their way to being used at least in autologous transplantation. We isolated cellular populations from placental tissue and umbilical cord using the explants method. The placental (PL) and umbilical cord (UC)-derived cells were cultured and expanded in appropriate conditions for generation of stem cells. We assessed the stemness characteristics of the tissue-isolated cells and compared them to an established MSCs line. For this purpose, we determined the immunophenotype, morphological and ultrastructural characteristics, as well as functional abilities of PL- and UC-derived cells. Flow cytometric evaluation of cells revealed presence of CD90, CD73, and CD105 stem cells markers, while the cells were negative for CD34, CD45 and HLA-DR. Immunocytochemical staining showed that 100% of PL- and UC-derived cells are positive for vimentin and CD105 expression, while cytokeratin was revealed in less than 10% in both tissue-isolated cells. Morphological and ultrastructural characteristics of cells exposed analogous cellular size and intracellular organization, similar to MSCs, but detailed view of UC-derived cells by transmission electron microscopy (TEM) demonstrated presence of intercellular junctions-desmosomes, similar to epithelial cells. Both PL- and UC-derived cells confirmed their trilineage potential, being able to differentiate into adipocytes, osteoblasts, and chondrocytes in different proportions. Flow chamber in vitro assay was used to determine to what extent PL- and UC-derived cells are able to adhere to substrates (VCAM and ICAM) and we showed progressively decreased adhesion of both cellular types, inversely proportional to the generated shear stress. We may conclude that explants-isolated placental and umbilical cord cells are endowed with characteristics of both epithelial and mesenchymal stem cells, and purification procedures are additionally required for safe use of these cells in diverse clinical applications.