Immature ovarian teratoma with gliomatosis peritonei, paraneoplastic hyponatremia and growing teratoma syndrome: a case report and literature review.

Introduction and relevance: Paraneoplastic hyponatremia is often secondary to syndrome of inappropriate antidiuretic hormone secretion (SIADH) by tumour cells. Immature ovarian teratomas (IOT) are uncommon and may present with SIADH. Case report: A 26-year-old female presented with a 3-month history of abdominal pain and constipation. Imaging identified a mixed solid-cystic right ovarian mass containing fat and peritoneal deposits. Biochemistry showed severe, refractory hyponatremia (117 mmol/l). She underwent diagnostic fertility-preserving right salpingo-oophorectomy and resection of peritoneal nodules with the aim to achieve symptom control and hyponatraemia resolution. Pathology revealed a FIGO Stage 2 Grade 2 IOT with extensive benign peritoneal gliomatosis. Initial management was conservative. After 6 months of active follow-up, a rise in AFP, and recurrent hyponatremia supported the decision to administer three cycles of Bleomycin-Etoposide-Cisplatin chemotherapy. One month later, given radiological disease progression despite satisfactory biomarker response, cytoreductive surgery with complete macroscopic resection was performed. Pathology consisted solely of peritoneal mature glial elements: a growing teratoma syndrome (GTS). The patient remains disease-free after 2 years of surveillance. Clinical discussion: Specimen histological assessment from the patient's initial surgery showed immature neuroectodermal tubules, which are thought to be the source of vasopressin secretion. The authors hypothesise that recurrent hyponatremia and rising AFP levels represented postoperative disease relapse. Biochemical response despite radiological disease progression was pathognomonic of a GTS. Conclusion: Paraneoplastic SIADH secondary to an IOT must be considered in female patients presenting with abdominal symptoms and hyponatremia. Management requires a multidisciplinary approach. Serum electrolytes are useful surveillance biomarkers supplementary to tumour markers.

Current and Emerging Strategies for Tubo-Ovarian Cancer Diagnostics.

Tubo-ovarian cancer is the most lethal gynaecological cancer. More than 75% of patients are diagnosed at an advanced stage, which is associated with poorer overall survival. Symptoms at presentation are vague and non-specific, contributing to late diagnosis. Multimodal risk models have improved the diagnostic accuracy of adnexal mass assessment based on patient risk factors, coupled with findings on imaging and serum-based biomarker tests. Newly developed ultrasonographic assessment algorithms have standardised documentation and enable stratification of care between local hospitals and cancer centres. So far, no screening test has proven to reduce ovarian cancer mortality in the general population. This review is an update on the evidence behind ovarian cancer diagnostic strategies.

COVID-19 and Hypertensive Disorders of Pregnancy (HDP): A Portuguese Multicentric Retrospective Cohort Study of HDP in SARS-CoV-2 Infected Patients.

BACKGROUND:  An increased incidence of hypertensive disorders of pregnancy (HDP) has been reported among pregnant women infected by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the pathogen behind coronavirus disease-19 (COVID-19). Although it is primarily a respiratory infection, the extra-pulmonary manifestations of COVID-19 mimic those found in preeclampsia (PE). Moreover, the two conditions share common risk factors and pathological mechanisms, hindering the ability to understand the interaction between them. Current literature on this topic is controversial and as there is an overlap of clinical and laboratory findings, HDP can be an overreported outcome in pregnant women with COVID-19. The aim of our study is to assess whether there is an association between maternal SARS-CoV-2 infection and HDP. METHODS: We designed a multicenter retrospective cohort study with data collected from five maternity hospitals in Almada, Porto, Lisboa, Penafiel and Coimbra, Portugal, between March 2020 and March 2021. We obtained a sample of 789 pregnant women who were followed up or delivered their babies in one of the participating centers. Each pregnant woman who tested positive for SARS-CoV-2 on a real-time polymerase chain reaction test -- exposure group (n= 263), was paired with two negative pregnant women (1:2), who received the same antenatal care and had similar gestational age and parity -- control group (n=526). Data were collected on maternal characteristics, medical history, obstetric outcomes, and delivery.  Outcomes: The primary outcome of our study is to assess the incidence of HDP in pregnant women infected and not infected by SARS-CoV-2. The secondary outcomes of our study are to assess the incidence of HDP across all COVID-19 severity subgroups and to assess whether SARS-CoV-2 infection in pregnancy modified the odds of a set of risk factors developing HDP.  Results: There was a slightly increased, but not statistically significant, incidence of PE (relative risk, RR, 1.33; 95% confidence interval, CI 0.68-2.57) in the SARS-CoV-2 positive group. There was no statistically significant association between having COVID-19 in pregnancy and developing PE/eclampsia/ hemolysis, elevated liver enzymes, and low platelets, HELLP syndrome [X2(1) = 0.732; p = 0.392] as well as developing gestational hypertension (GH) [X2(1) = 0.039; p = 1]. There was no statistically significant association [X2(2) = 0.402; p = 0.875), [X2(2) = 1.529; p = 0.435] between COVID-19 severity and incidence of HDP. The SARS-CoV-2 infection did not modify the odds of each maternal risk factor causing HDP.  Conclusion: Our study did not demonstrate an association between maternal COVID-19 and HDP. We did not observe a significantly increased incidence of HDP in pregnant women infected by SARS-CoV-2. As current literature is controversial on this topic, clinicians should be aware that HDP is a possible complication of maternal SARS-CoV-2 infection and further research studies urge to better assess the association between COVID-19 in pregnancy and HDP.

Epigenetic and Drug Response Modulation of Epigalocaten-In-3-Gallate in Staphylococcus aureus with Divergent Resistance Phenotypes.

Healthcare-associated methicillin-resistant Staphylococcus aureus infections represent extremely high morbidity and mortality rates worldwide. We aimed to assess the antimicrobial potential and synergistic effect between Epigalocatenin-3-gallate (EGCG) and different antibiotics in S. aureus strains with divergent resistance phenotypes. EGCG exposure effects in epigenetic and drug resistance key modulators were also evaluated. S. aureus strains (n = 32) were isolated from infected patients in a Lisbon hospital. The identification of the S. aureus resistance phenotype was performed through automatized methods. The antibiotic synergistic assay was performed through disk diffusion according to EUCAST guidelines with co-exposure to EGCG (250, 100, 50 and 25 µg/mL). The bacteria's molecular profile was assessed through FTIR spectroscopy. The transcriptional expression of OrfX, SpdC and WalKR was performed by using qRT-PCR. FTIR-spectroscopy analysis enabled the clear discrimination of MRSA/MSSA strains and the EGCG exposure effect in the bacteria's molecular profiles. Divergent resistant phenotypes were associated with divergent transcriptional expression of the epigenetic modulator OrfX, particularly in MRSA strains, as well as the key drug response modulators SpdC and WalKR. These results clearly demonstrate that EGCG exposure alters the expression patterns of key epigenetic and drug response genes with associated divergent-resistant profiles, which supports its potential for antimicrobial treatment and/or therapeutic adjuvant against antibiotic-resistant microorganisms.

Fetal Deaths in SARS-CoV-2-Infected Pregnant Women: A Portuguese Case Series.

Introduction: Stillbirth has been documented as an outcome of SARS-CoV-2 infection in pregnancy. Placental hypoperfusion and inflammation secondary to maternal immune response seem to play a role in the cascade of events that contribute to fetal death. The aim of our study is to report a perinatal outcome of SARS-CoV-2 infection in pregnancy adding information to the pool of data on COVID-19 pregnancy outcomes. Case Presentation. This is the first stillbirth case series occurring in pregnant women infected with SARS-CoV-2 in a Portuguese cohort. Between April 2020 and March 2021, we had 2680 births in our centre, of which 130 (4.95%) involved mothers infected with SARS-CoV-2. Of total births, there were 14 stillbirths (0.52%), accounting for the highest stillbirth rate we have had in the last 5 years. Among these 14 stillbirths, 5 (35.71%) occurred in SARS-CoV-2-infected mothers. We report the clinical features and placental histopathologic findings of 4 stillbirth cases that occurred in our hospital. Discussion. The stillbirth rate among SARS-CoV-2-infected pregnant women (5/130; 3.84%) was significantly increased compared to noninfected patients (9/2550; 0.35%). Most women (3/4) were asymptomatic for COVID-19, a surprising outcome, given the current literature. All cases had histologic exams showing placental signs of vascular malperfusion, although we acknowledge that 3/5 had obstetric conditions related to placental vascular impairment such as preeclampsia and HELLP syndrome. Conclusion: Stillbirth can be a perinatal consequence of SARS-CoV-2 infection in pregnancy, even in asymptomatic patients. We urge more studies to explore the association between SARS-CoV-2 infection and the risk of stillbirth.

Drug Resistance and Epigenetic Modulatory Potential of Epigallocatechin-3-Gallate Against Staphylococcus aureus.

Antimicrobial resistance of human pathogens, such as methicillin-resistant Staphylococcus aureus, is described by the World Health Organization as a health global challenge and efforts must be made for the discovery of new effective and safe compounds. This work aims to evaluate epigallocatechin-3-gallate (EGCG) epigenetic and modulatory drug potential against S. aureus in vitro and in vivo. S. aureus strains were isolated from commensal flora of healthy volunteers. Antibiotic susceptibility and synergistic assay were assessed through disk diffusion accordingly to EUCAST guidelines with and without co-exposure to EGCG at final concentrations of 250 µg/ml, 100 µg/ml, 50 µg/ml, and 25 µg/ml. Transcriptional expression of orfx, spdC, and WalKR was performed through qRT-PCR. A 90-day interventional study was performed with daily consumption of 225 mg of EGCG. Obtained data revealed a high prevalence of S. aureus colonization in healthcare workers and clearly demonstrated the antimicrobial and synergistic potential of EGCG as well as divergent resistant phenotypes associated with altered transcriptional expression of epigenetic and drug response modulators genes. Here, we demonstrate the potential of EGCG for antimicrobial treatment and/or therapeutic adjuvant against antibiotic-resistant microorganisms and report divergent patterns of epigenetic modulators expression associated with phenotypic resistance profiles.