SARS CoV-2 infection as a risk factor of preeclampsia and pre-term birth. An interplay between viral infection, pregnancy-specific immune shift and endothelial dysfunction may lead to negative pregnancy outcomes.

BACKGROUND: Since SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) was first identified as the cause of Coronavirus disease 19 (COVID-19) it has caused over 649,147,421 infections and over 6,730,382 deaths worldwide. SARS-CoV-2 presents higher infectivity than other coronaviridae (MERS-CoV and SARS-CoV). Pregnant patients, according to previous studies are at high risk of severe COVID-19 course and negative pregnancy outcomes (pre-term birth, low birth weight, preeclampsia, operative delivery and ICU admission with need for mechanical ventilation). METHODS: In this review we focus on the pathophysiology of subcellular changes in COVID-19 and try bring to light the aspects that occur in physiological pregnancy that may cause higher risk of SARS-CoV-2 infection and severe COVID-19 course. RESULTS: Knowledge of potential interplay between viral infection and physiological changes in pregnancy may point us in the direction of future prophylaxis and treatment in this special population.Key MessagesSARS-CoV-2 having affinity to ACE-2 and causing it's downregulation receptor may cause endothelial injury leading to compliment activation and formation of NETs, together with RAS dysregulation this may cause preeclampsia to develop in pregnant patients.PTB may occur in patients as an effect of SARS-CoV-2 infection in first or second trimester as an effect of TLR4 pathway dysregulation with lower levels of IFNß.

Pregnancy as a Risk Factor of Severe COVID-19.

Since first being identified in December 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as an etiological agent behind Coronavirus disease 19 (COVID-19), has caused three waves of a global pandemic, with a fourth in progress. Despite its high percentage of asymptomatic and low-symptomatic courses of illness, the SARS-CoV-2 pandemic has claimed a higher death toll than the SARS-CoV and MERS-CoV epidemics because of its high infectivity when compared to the other coronaviruses. High COVID-19 mortality is associated with age and other coexisting morbidities, as well as healthcare quality. According to several studies, pregnant women are at a higher risk of severe COVID-19 infection and adverse pregnancy outcomes (caesarean delivery, pre-term birth, low birth weight, preeclampsia, ICU admission, and need for mechanical ventilation). In our review of recent literature, we focused on the effects of COVID-19 in pregnant women, emphasizing the subcellular pathophysiology of SARS-CoV-2. In this paper, we concentrate on the pathophysiology of sub-cellular changes in COVID-19 and endeavor to highlight the aspects that manifest in physiological pregnancy and potentially create a higher risk of SARS-CoV-2 infection and acute COVID-19 symptoms. Understanding how pregnancy-associated changes can cause a synergistic effect with COVID-19 may point us in the right direction for future prophylaxis and treatment for women undergoing COVID-19 during pregnancy.

The Role of Inflammation in the Pathogenesis of Preeclampsia.

Preeclampsia (PE) affects 5-8% of pregnant women, and it is the major cause of perinatal morbidity and mortality. It is defined as arterial hypertension in women after 20 weeks of gestation which cooccurs with proteinuria (300 mg/d) or as arterial hypertension which is accompanied by one of the following: renal failure, liver dysfunction, hematological or neurological abnormalities, intrauterine growth restriction, or uteroplacental insufficiency. Currently, pathophysiology of preeclampsia poses a considerable challenge for perinatology. Preeclampsia is characterized by excessive and progressive activation of the immune system along with an increase in proinflammatory cytokines and antiangiogenic factors in fetoplacental unit as well as in vascular endothelium in pregnant women. A single, major underlying mechanism of preeclampsia is yet to be identified. This paper discusses the current understanding of the mechanisms which underlie the development of the condition. Some significant factors responsible for PE development include oxidative stress, abnormal concentration and activity in mononuclear phagocytic system, altered levels of angiogenic and antiangiogenic factors, and impaired inflammatory response triggered by inflammasomes. Detailed understanding of pathophysiology of inflammatory process in PE can largely contribute to new, targeted anti-inflammatory therapies that may improve perinatal outcomes in PE patients.

Perspectives in HPV Secondary Screening and Personalized Therapy Basing on Our Understanding of HPV-Related Carcinogenesis Pathways.

As cervical cancer is one of the most common malignancies in women worldwide even with present screening methods, the incidence in most developed countries is not decreasing for the last 15-20 years. A shift has been observed in the age of diagnosis in favour of younger women, and treatment of already developed cervical cancer is a challenge for surgeons. It is imperative to find new diagnostic methods for accurately pointing out patients at high risk of developing malignant disease and developing personalized treatment. Since cervical cancer is almost exclusively associated with HPV infection, understanding changes happening in an infected cell may prove invaluable for search of such methods, but it may also prove helpful in the diagnosis and treatment of other anogenital and nasopharyngeal region cancers. This review follows HPV-related changes in infected cell biology to point what potential markers and targets for therapy are in option when dealing with HPV-related diseases.

The Influence of Maternal-Foetal Parameters on Concentrations of Zonulin and Calprotectin in the Blood and Stool of Healthy Newborns during the First Seven Days of Life. An Observational Prospective Cohort Study.

BACKGROUND: It can be hypothetically assumed that maternal and perinatal factors influence the intestinal barrier. METHODS: The study was conducted with 100 healthy, full-term newborns breastfed in the first week of life, with similar analyses for their mothers. Zonulin and calprotectin levels were used as intestinal permeability markers. RESULTS: The median (range) zonulin concentrations (ng/mL) were in mothers: serum, 21.39 (6.39⁻57.54); stool, 82.23 (42.52⁻225.74); and newborns: serum cord blood, 11.14 (5.82⁻52.34); meconium, 54.15 (1.36⁻700.65); and stool at age seven days, 114.41 (29.38⁻593.72). Calprotectin median (range) concentrations (µg/mL) in mothers were: stool, 74.79 (3.89⁻211.77); and newborns: meconium, 154.76 (6.93⁻8884.11); and stool at age seven days 139.12 (11.89⁻627.35). The use of antibiotics during pregnancy resulted in higher zonulin concentrations in umbilical-cord serum and calprotectin concentrations in newborn stool at seven days, while antibiotic therapy during labour resulted in higher zonulin concentrations in the stool of newborns at seven days. Zonulin concentrations in the stool of newborns (at seven days) who were born via caesarean section were higher compared to with vaginal birth. With further analyses, caesarean section was found to have a greater effect on zonulin concentrations than prophylactic administration of antibiotics in the perinatal period. Pregnancy mass gain >18 kg was associated with higher calprotectin concentrations in maternal stool. Body Mass Index (BMI) increase >5.7 during pregnancy was associated with decreased zonulin concentrations in maternal stool and increased calprotectin concentrations in stool of mothers and newborns at seven days. There was also a negative correlation between higher BMI increase in pregnancy and maternal zonulin stool concentrations and a positive correlation between BMI increase in pregnancy and maternal calprotectin stool concentrations. CONCLUSION: Maternal-foetal factors such as caesarean section, antibiotic therapy during pregnancy, as well as change in mother's BMI during pregnancy may increase intestinal permeability in newborns. Changes in body mass during pregnancy can also affect intestinal permeability in mothers. However, health consequences associated with increased intestinal permeability during the first days of life are unknown. Additionally, before the zonulin and calprotectin tests can be adopted as universal diagnostic applications to assess increased intestinal permeability, validation of these tests is necessary.

Selected features of breast and peritoneal cancers diagnosed in BRCA1 carriers after risk-reducing salpingo-oophorectomy.

BACKGROUND: Since more than two decades Risk-reducing salpingo-oophorectomy (RRSO) is recommended and widely accepted by BRCA1/2 carriers as a method reducing ovarian cancer risk and improving survival rate. After RRSO, there remains a risk of breast cancer and peritoneal cancer. The characteristics of these neoplasms are not well known. In this study, we determined the selected parameters such as age at cancer diagnosis, time from RRSO to the diagnosis of cancer, and significance of BRCA1 mutation type in patients diagnosed with breast or peritoneal cancer during postoperative follow-up. METHODS: The material comprised of 195 BRCA1 carriers who performed RRSO between years 1999-2012. In this period, 16 patients developed cancer (6-primary breast cancer, 3-contralateral breast cancer, 5-relapse of breast cancer, 2-peritoneal cancer). They were subject of the further analysis. RESULTS: During the follow-up period mean age of patients after RRSO at the time of cancer diagnosis was 53.19. The mean age of patients diagnosed with primary breast cancer was 50, contralateral breast cancer - 58.67, recurrence of breast cancer - 51 and peritoneal cancer 60. The mean time periods from RRSO to the diagnosis of primary, contralateral, recurrence breast cancer were 53, 58.67 and 25,4 months respectively and of peritoneal cancer 46 months. BRCA1 c.5266dupC mutation carriers demonstrated significantly shorter time of cancer development compared to patients carrying c.181T > G and c.4035delA mutations. Peritoneal cancer was only observed in two c.181T > G BRCA1 mutation carriers. CONCLUSIONS: The mean age of cancer diagnosis and the mean time periods from RRSO to the diagnosis of cancer are similar to those observed by other researchers. The carriers of c.181T > G and c.5266dupC BRCA1 mutation should be the subject further studies in context of breast and peritoneal cancer risk or time of cancer development after RRSO, respectively.

Clinical efficacy of p16/Ki-67 dual-stained cervical cytology in secondary prevention of cervical cancer.

Cervical cancer is the third most common malignant neoplasm in women worldwide. HPV infection is the necessary factor for the cancer to develop. HPV DNA can be integrated into the genome of squamous epithelium and cause transcription of the viral oncoproteins and development of invasive cancer within 15-20 years. We assessed ICC co-expression of p16/Ki-67 proteins in smears collected from the uterine cervix and the association between p16/Ki-67 co-expression and cytologic and histologic results. Samples were collected from 93 women using liquid based cytology (LBC). Two microscopic slides were prepared: for Papanicolaou staining and ICC staining. Biopsy samples were collected from 43 women. Diagnosis of CIN 2+ was the endpoint of the study. p16/Ki-67 positive cells were found in women with: 1) a cytology result of ASC-US (3.59%), LSIL (2.22%), ASC-H (21.92%), HSIL (33.18%), SCC (72.22%) or NILM (3.44%); 2) a histopathologic result of CIN 1 (2.13%), CIN 2 (19.93%), CIN 3 (23.22%), SCC (69.72%) or normal histology (7.58%). p16/Ki-67 dual staining can increase the efficiency of screening methods and indicate women in whom further diagnostic procedures are required or those with extremely low risk of cancer. Sparing protocols will have a significant role in women of reproductive age.