Individualized Follow-up of Pregnant Women with Asymptomatic Autoimmune Thyroid Disease

Maternal hormones are essential for the normal fetal development during pregnancy. Autoimmune thyroid disease is a frequent pathology in our iodine replete region. The aim of this study is to evaluate the occurrence of subclinical hypothyroidism (SCH) in cases with known autoimmune thyroid disease, which were in a euthyroid state prior to pregnancy, and to assess the association between supplemental treatments administered and the outcome of the pregnancy. The study is a prospective interventional controlled study. The two cohorts comprise the interventional group, consisting of 109 pregnant women with known autoimmune asymptomatic thyroid disease, without any levothyroxine (LT4) treatment and an aged-matched control group, with an unknown thyroid disease. After the pregnancy, a monthly evaluation of TSH, FT3, and FT4 was performed. Offspring evaluation was made at birth time. 88.8% of the women developed SCH in the first four weeks of pregnancy. Average LT4 doses increased as the pregnancy progressed. The monthly adjustment was 12.5 or 25 μg. All SCH cases developed in the first trimester of pregnancy. There was no significant difference regarding the gestational week, weight, or length at birth between the interventional group and controls, when TSH values were in the optimal range, during the whole pregnancy. Premature birth was described in one case in the interventional group

The Efficacy of Convalescent Plasma Use in Critically Ill COVID-19 Patients

Background and Objectives: On 24 March 2020, the United States Food and Drug Administration (FDA) announced the approval of convalescent plasma therapy for critically ill patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as an emergency investigational new drug. This pilot study from Romania aimed to determine if convalescent plasma transfusion can be beneficial in the treatment of selected critically ill patients diagnosed with a SARS-CoV-2 infection. Materials and Methods: Donor and receiver eligibility for critically ill coronavirus disease 2019 (COVID-19) patients was based on Romanian guidelines issued at the time of the study. Here, we describe the evolution of a total of five eligible patients diagnosed with COVID-19 who received convalescent plasma (CP) in Romania. Results: In spite of our efforts and convalescent plasma administration, three of the five patients did not survive, while the other two recovered completely. Over the course of our five-day laboratory record, the surviving patients had significantly lower values for C-reactive protein, interleukin-6, and white blood cells. Conclusions: This pilot study provides insufficient evidence to determine the efficacy of convalescent plasma use as a therapeutic option for critically ill COVID-19 patients

A Cross-Sectional Analysis of Paternal Intimacy Problems, Stress Levels, and Satisfaction from Families with Children Born with Mucoviscidosis

There is an increasing interest in father–child interactions and their effects. Due to the rising number of working mothers, marital interruptions, divorces, and child custody arrangements, paternal duties and the relevance of fathering continue to be re-evaluated. As there are rising expectations for men to undertake more childcare and household responsibilities, it was hypothesized that the presence of a disabled or chronically ill child would have a significant impact on the couple’s future family situation, marital conduct due to paternal dissatisfaction, and increased stress levels. Therefore, the purpose of this study was to examine paternal intimacy problems, stress levels, and couple satisfaction inside families that have children with cystic fibrosis. The study followed a cross-sectional design with five questionnaires that were answered by a total of 107 fathers of children with cystic fibrosis from the “cases” group as the reference group, and 124 fathers of healthy children from the “control” group. The statistically significant findings of the current study show that men who were taking care of their child with mucoviscidosis engaged less frequently in sexual activity. A significantly higher number of these respondents were smokers. A higher proportion of them reported marital distress (OR = 2.54) and inhibited sexual desire (OR = 2.02), all in association with a higher number of men taking psychiatric medication (7.5% vs. 1.6%). More than 40% of all respondents declared high levels of general stress and parenting distress, while the most frequently used coping mechanism for stress was avoidance-oriented (45.8% vs. 25.8%). Other important findings were the high levels of dissatisfaction and lower levels of marital quality on the SII scale, equivalent to the intimacy problems on the MIQ scale. It is likely that paternal stress is higher when parenting children with cystic fibrosis, and the lack of intervention in this vulnerable group seem to be associated with intimacy problems, couple dissatisfaction, and maladaptive coping mechanisms. It is recommended that these concerns should not only be raised for the mothers of children with mucoviscidosis, but also for the child’s father or the male caretaker partner since they might experience the same problems as the opposite gender

p16/Ki-67 dual staining has a better accuracy than human papillomavirus (HPV) testing in women under 30 years old

Due to a high rate of transient human papillomavirus (HPV) infection, HPV genotyping has a low specificity for high-grade cervical lesions, especially in young women. p16/Ki-67 dual immunohistochemical staining can also be used for the detection of oncogenic changes in cervical cells. Our aim was to compare the performance of p16/Ki-67 dual staining and HPV genotyping in the detection of high-grade cervical lesions in patients with atypical squamous cells of undetermined significance (ASCUS)/low-grade squamous intraepithelial lesion (LSIL) on Pap smear. We retrospectively analyzed 310 patients with ASCUS/LSIL on Pap smear, who underwent colposcopy. Among these, 161 patients with suspected lesions detected by colposcopy were referred to biopsy. HPV genotyping by LINEAR ARRAY HPV Genotyping Test (CE-IVD) and p16/Ki-67 dual staining by CINtec PLUS Cytology kit was performed prior to cervical biopsy. The overall sensitivity and specificity of HPV genotyping for the detection of cervical intraepithelial neoplasia (CIN) 2-3 was 79% and 72%, respectively in patients with ASCUS, and 85% and 64%, respectively in patients with LSIL. For p16/ki-67 test, sensitivity and specificity rate was 66% and 93%, respectively in ASCUS and 59% and 79%, respectively in LSIL group. The specificity of p16/Ki-67 staining was significantly higher in both groups in patients aged 30 years old (p < 0.001). Our results showed that p16/Ki-67 dual staining has a higher specificity compared to HPV genotyping, especially in patients under 30 years old. This indicates the usefulness of p16/Ki-67 testing in the triage of patients with ASCUS/LSIL and <30 years old, prior to the referral to colposcopy and biopsy

The Efficiency of a Uterine Isthmus Tourniquet in Minimizing Blood Loss during a Myomectomy—A Prospective Study

Background and Objectives: The objective of this study was to assess the effectiveness of using a peri-cervical tourniquet in reducing blood loss during a laparoscopic myomectomy. Materials and Methods: This prospective study evaluated the impact of performing a concomitant tourniquet placement during a laparoscopic myomectomy (LM). A total of 60 patients were randomly allocated to one of two groups: 30 patients who underwent an LM with a tourniquet placement (the TLM group) and 30 patients who benefited from a standard LM (the SLM group). This study’s main objective was to evaluate the impact of tourniquet use on perioperative blood loss, which is quantified as the difference in the pre- and postoperative hemoglobin levels (Delta Hb) and the postoperative blood transfusion rate. Results: The mean Delta Hb was statistically lower in the TLM group compared to the SLM group: 1.38 g/dL vs. 2.41 g/dL (p p = 0.02). All four patients that required a blood transfusion were from the SLM group. On average, the peri-cervical tourniquet fastening time was 10.62 min (between 7 and 15 min), with no significant impact on the overall operative time: 98.50 min for the TLM group compared to 94.66 min for the SLM group. Conclusions: Fastening a tourniquet during a laparoscopic myomectomy is a valuable technique to effectively control intraoperative bleeding and enhance surgical outcomes

A Cross-Sectional Study of the Marital Attitudes of Pregnant Women at Risk for Cystic Fibrosis and Psychological Impact of Prenatal Screening

Cystic fibrosis (CF) is one of the most frequent genetic disorders in those with Northern European ancestry. Prenatal testing for cystic fibrosis may be used to plan and prepare for the birth of a child with the disease or to determine whether to terminate the pregnancy. The accessibility of prenatal detection for women with a high genetic risk of delivering a child with cystic fibrosis is determined by CF carriers and those affected by the disease. Moreover, prenatal testing for CF is mainly dependent on invasive diagnostic tests that can influence the mental health of the pregnant woman, and it is assumed that the birth of a CF child will have a serious influence on the couple&rsquo;s subsequent family planning and marital behavior. The purpose of this research was to examine the marital attitudes of women at risk for cystic fibrosis and the psychological effect of screening for CF among pregnant women. The study followed a cross-sectional design with five questionnaires comprising Prenatal Attachment Interview (PAI), Maternal Antenatal Attachment Scale (MAAS), Pregnancy-Related Anxiety Questionnaire (PRAQ-R2), the Prenatal Psychosocial Profile (PPP), and the Marital Intimacy Questionnaire (MIQ). A total of 84 pregnant women were included in the &ldquo;carriers&rdquo; group for CFTR and 91 in the &ldquo;non-carrier&rdquo; group. CFTR-carrier mothers were likely to be more affectionate to the fetus, with better maternal&ndash;fetal quality and intensity of attachment. The same group of pregnant women was less scared of giving birth or worried about bearing a physically or mentally handicapped child compared to women who were expecting the prenatal diagnosis test for being at risk of delivering a newborn with malformations. CFTR-carrier pregnant women did not score significantly different results in the Prenatal Psychosocial Profile regarding stress levels, social support, and self-esteem. It was also found that intimacy and consensus problems inside the marriage were significantly more often experienced by CFTR carriers. Based on the current findings, it is likely that CFTR-carrier mothers have a better perception of the possible pregnancy outcomes by knowing their abnormal gene carrier status. Therefore, the psychological impact of invasive diagnostic tests is lower in this category compared with those who are unaware of the possible pregnancy outcomes. However, we promote a future analysis for pregnant women with moderate risk of giving birth to a child with single-gene mutations such as cystic fibrosis or other congenital malformations that undergo noninvasive prenatal diagnosis tests, as they become more accurate and might cause lower pre-diagnosis stress levels

Calcium, Magnesium, and Zinc Supplementation during Pregnancy: The Additive Value of Micronutrients on Maternal Immune Response after SARS-CoV-2 Infection

Magnesium may contribute to the immune response during and after SARS-CoV-2 infection by acting as a cofactor for immunoglobulin production and other processes required for T and B cell activity. Considering magnesium as a recommended dietary supplement during pregnancy and the possible role of magnesium deficiency in COVID-19 and its complications, the current study sought to determine the effect of magnesium and magnesium-containing nutritional supplements on the immune response following SARS-CoV-2 infection in pregnant women, as well as to observe differences in pregnancy outcomes based on the supplements taken during pregnancy. The study followed a cross-sectional design, where patients with a history of SARS-CoV-2 infection during their pregnancy were surveyed for their preferences in nutritional supplementation and their profile compared with existing records from the institutional database. A cohort of 448 pregnant women with COVID-19 during 22 months of the pandemic was assembled, out of which 13.6% took a magnesium-only supplement, and 16.5% supplemented their diet with a combination of calcium, magnesium, and zinc. Around 60% of patients in the no-supplementation group had the SARS-CoV-2 anti-RBD lower than 500 U/mL, compared with 50% in those who took magnesium-based supplements. A quantity of magnesium >450 mg in the taken supplements determined higher levels of antibody titers after COVID-19. Low magnesium dosage (p-value = 0.003). The observed findings suggest supplementing the nutritional intake of pregnant women with magnesium-based supplements to determine higher levels of SARS-CoV-2 anti-RBD antibodies, although causality remains unclear

Human papilloma virus (HPV) integration signature in Cervical Cancer: identification of MACROD2 gene as HPV hot spot integration site

Background: Cervical cancer (CC) remains a leading cause of gynaecological cancer-related mortality with infection by human papilloma virus (HPV) being the most important risk factor. We analysed the association between different viral integration signatures, clinical parameters and outcome in pre-treated CCs. Methods: Different integration signatures were identified using HPV double capture followed by next-generation sequencing (NGS) in 272 CC patients from the BioRAIDs study [NCT02428842]. Correlations between HPV integration signatures and clinical, biological and molecular features were assessed. Results: Episomal HPV was much less frequent in CC as compared to anal carcinoma (p 300 different HPV-chromosomal junctions (inter- or intra-genic). The most frequent integration site in CC was in MACROD2 gene followed by MIPOL1/TTC6 and TP63. HPV integration signatures were not associated with histological subtype, FIGO staging, treatment or PFS. HPVs were more frequently episomal in PIK3CA mutated tumours (p = 0.023). Viral integration type was dependent on HPV genotype (p < 0.0001); HPV18 and HPV45 being always integrated. High HPV copy number was associated with longer PFS (p = 0.011). Conclusions: This is to our knowledge the first study assessing the prognostic value of HPV integration in a prospectively annotated CC cohort, which detects a hotspot of HPV integration at MACROD2; involved in impaired PARP1 activity and chromosome instability

Clinical and genetic landscape of treatment naive cervical cancer: Alterations in PIK3CA and in epigenetic modulators associated with sub-optimal outcome

International audienceBACKGROUND: There is a lack of information as to which molecular processes, present at diagnosis, favor tumour escape from standard-of-care treatments in cervical cancer (CC). RAIDs consortium (www.raids-fp7.eu), conducted a prospectively monitored trial, [BioRAIDs (NCT02428842)] with the objectives to generate high quality samples and molecular assessments to stratify patient populations and to identify molecular patterns associated with poor outcome.METHODS: Between 2013 and 2017, RAIDs collected a prospective CC sample and clinical dataset involving 419 participant patients from 18 centers in seven EU countries. Next Generation Sequencing has so far been carried out on a total of 182 samples from 377 evaluable (48%) patients, allowing to define dominant genetic alterations. Reverse phase protein expression arrays (RPPA) was applied to group patients into clusters. Activation of key genetic pathways and protein expression signatures were tested for associations with outcome.FINDINGS: At a median follow up (FU) of 22 months, progression-free survival rates of this FIGO stage IB1-IV population, treated predominantly (87%) by chemoradiation, were65•4% [CI95%: 60•2-71.1]. Dominant oncogenic alterations were seen in PIK3CA (40%), while dominant suppressor gene alterations were seen in KMT2D (15%) and KMT2C (16%). Cumulative frequency of loss-of-function (LOF) mutations in any epigenetic modulator gene alteration was 47% and it was associated with PIK3CA gene alterations in 32%. Patients with tumours harboring alterations in both pathways had a significantly poorer PFS. A new finding was the detection of a high frequency of gains of TLR4 gene amplifications (10%), as well as amplifications, mutations, and non-frame-shift deletions of Androgen receptor (AR) gene in 7% of patients. Finally, RPPA protein expression analysis defined three expression clusters.INTERPRETATION: Our data suggests that patient population may be stratified into four different treatment strategies based on molecular markers at the outset. FUND: European Union's Seventh Program grant agreement No 304810