Prevalence and prenatal ultrasound detection of clubfoot in a non-selected population: an analysis of 549 931 births in Tuscany

Objective: To evaluate the prevalence and prenatal ultrasound detection of clubfoot in Tuscany during a period of 20 years. Methods: This is a descriptive analysis on data from the Tuscan register of congenital defects, covering a 20-year period from 1992 to 2011. The Tuscan registry of congenital defects is a population-based register for the epidemiologic surveillance of congenital anomalies. The study included all cases of pre- or postnatally diagnosed clubfoot (isolated clubfoot and cases associated with other congenital defects). Overall prevalence and pre-natal detection rates were calculated. Results: Among the 549 931 deliveries recorded in Tuscany between 1992 and 2011, 858 cases of clubfoot were registered, with a prevalence of 1.56/1000. Seventy-eight percent of cases were isolated. The detection rate was higher when the defect was associated with other anomalies compared to isolated forms. Over the study period, there was a substantial improvement in the prenatal detection of clubfoot (from 11 to 31% overall). For isolated forms, detection rate improved from 4 to 16%, and for cases associated with other congenital defects, it increased from 43 to 73%. Conclusion: Prevalence of clubfoot in Tuscany is 1.56 per 1000 births, in agreement with the incidence reported in epidemiological studies in Europe. Prenatal detection of clubfoot improved over time. The detection rate was higher in cases associated with other anomalies

Relationship between cervical dilation and time to delivery in women with preterm labor

Background: Early recognition of the signs and symptoms of preterm labor (PTL) is important in order to establish treatment. Our aim was to determine the relation between cervical dilatation and time interval from admission to delivery in women with preterm labor. Materials and Methods: A retrospective cohort study was conducted on 83 singleton gestations admitted for preterm labor between 24 weeks and 34 weeks, who subsequently delivered preterm. Women were categorized into three groups of cervical dilatation (0-2 cm, 3-6 cm, >6 cm) and the time interval from admission to delivery was compared. Cox regression analysis was performed to assess the association between cervical dilatation and time interval from admission to delivery. The other variables examined were gestational age (GA) at admission and length of the cervix, when performed. Results: The time interval from admission to delivery was significantly shorter in women with higher dilatation of the cervix (p < 0.02) and in those admitted at a more advanced gestational age (p < 0.05). Forty-eight percent of women with cervical dilatation 0-2 cm delivered in the first 48 h compared to 85% of the women with a dilatation of 3-6 cm. No significant association was found between the length of the cervix and the time interval to delivery. Conclusion: Dilatation of the cervix and gestational age at admission are associated with the time interval to delivery in women with preterm labor. The assessment of the length of the cervix is unlikely to add clinical information in women with an already dilated cervix

Sudden Unexpected Deaths and Vaccinations during the First Two Years of Life in Italy: A Case Series Study

Background The signal of an association between vaccination in the second year of life with a hexavalent vaccine and sudden unexpected deaths (SUD) in the two days following vaccination was reported in Germany in 2003. A study to establish whether the immunisation with hexavalent vaccines increased the short term risk of SUD in infants was conducted in Italy. Methodology/Principal Findings The reference population comprises around 3 million infants vaccinated in Italy in the study period 1999–2004 (1.5 million received hexavalent vaccines). Events of SUD in infants aged 1–23 months were identified through the death certificates. Vaccination history was retrieved from immunisation registries. Association between immunisation and death was assessed adopting a case series design focusing on the risk periods 0–1, 0–7, and 0–14 days after immunisation. Among the 604 infants who died of SUD, 244 (40%) had received at least one vaccination. Four deaths occurred within two days from vaccination with the hexavalent vaccines (RR = 1.5; 95% CI 0.6 to 4.2). The RRs for the risk periods 0–7 and 0–14 were 2.0 (95% CI 1.2 to 3.5) and 1.5 (95% CI 0.9 to 2.4). The increased risk was limited to the first dose (RR = 2.2; 95% CI 1.1 to 4.4), whereas no increase was observed for the second and third doses combined. Conclusions The RRs of SUD for any vaccines and any risk periods, even when greater than 1, were almost an order of magnitude lower than the estimates in Germany. The limited increase in RRs found in Italy appears confined to the first dose and may be partly explained by a residual uncontrolled confounding effect of age

A machine-learning based bio-psycho-social model for the prediction of non-obstructive and obstructive coronary artery disease

Background: Mechanisms of myocardial ischemia in obstructive and non-obstructive coronary artery disease (CAD), and the interplay between clinical, functional, biological and psycho-social features, are still far to be fully elucidated. Objectives: To develop a machine-learning (ML) model for the supervised prediction of obstructive versus non-obstructive CAD. Methods: From the EVA study, we analysed adults hospitalized for IHD undergoing conventional coronary angiography (CCA). Non-obstructive CAD was defined by a stenosis &lt; 50% in one or more vessels. Baseline clinical and psycho-socio-cultural characteristics were used for computing a Rockwood and Mitnitski frailty index, and a gender score according to GENESIS-PRAXY methodology. Serum concentration of inflammatory cytokines was measured with a multiplex flow cytometry assay. Through an XGBoost classifier combined with an explainable artificial intelligence tool (SHAP), we identified the most influential features in discriminating obstructive versus non-obstructive CAD. Results: Among the overall EVA cohort (n = 509), 311 individuals (mean age 67 ± 11&nbsp;years, 38% females; 67% obstructive CAD) with complete data were analysed. The ML-based model (83% accuracy and 87% precision) showed that while obstructive CAD was associated with higher frailty index, older age and a cytokine signature characterized by IL-1β, IL-12p70 and IL-33, non-obstructive CAD was associated with a higher gender score (i.e., social characteristics traditionally ascribed to women) and with a cytokine signature characterized by IL-18, IL-8, IL-23. Conclusions: Integrating clinical, biological, and psycho-social features, we have optimized a sex- and gender-unbiased model that discriminates obstructive and non-obstructive CAD. Further mechanistic studies will shed light on the biological plausibility of these associations. Clinical trial registration: NCT02737982

The Sex-Specific Detrimental Effect of Diabetes and Gender-Related Factors on Pre-admission Medication Adherence Among Patients Hospitalized for Ischemic Heart Disease: Insights From EVA Study

Background: Sex and gender-related factors have been under-investigated as relevant determinants of health outcomes across non-communicable chronic diseases. Poor medication adherence results in adverse clinical outcomes and sex differences have been reported among patients at high cardiovascular risk, such as diabetics. The effect of diabetes and gender-related factors on medication adherence among women and men at high risk for ischemic heart disease (IHD) has not yet been fully investigated.Aim: To explore the role of sex, gender-related factors, and diabetes in pre-admission medication adherence among patients hospitalized for IHD.Materials and Methods: Data were obtained from the Endocrine Vascular disease Approach (EVA) (ClinicalTrials.gov Identifier: NCT02737982), a prospective cohort of patients admitted for IHD. We selected patients with baseline information regarding the presence of diabetes, cardiovascular risk factors, and gender-related variables (i.e., gender identity, gender role, gender relations, institutionalized gender). Our primary outcome was the proportion of pre-admission medication adherence defined through a self-reported questionnaire. We performed a sex-stratified analysis of clinical and gender-related factors associated with pre-admission medication adherence.Results: Two-hundred eighty patients admitted for IHD (35% women, mean age 70), were included. Around one-fourth of the patients were low-adherent to therapy before hospitalization, regardless of sex. Low-adherent patients were more likely diabetic (40%) and employed (40%). Sex-stratified analysis showed that low-adherent men were more likely to be employed (58 vs. 33%) and not primary earners (73 vs. 54%), with more masculine traits of personality, as compared with medium-high adherent men. Interestingly, women reporting medication low-adherence were similar for clinical and gender-related factors to those with medium-high adherence, except for diabetes (42 vs. 20%, p = 0.004). In a multivariate adjusted model only employed status was associated with poor medication adherence (OR 0.55, 95%CI 0.31–0.97). However, in the sex-stratified analysis, diabetes was independently associated with medication adherence only in women (OR 0.36; 95%CI 0.13–0.96), whereas a higher masculine BSRI was the only factor associated with medication adherence in men (OR 0.59, 95%CI 0.35–0.99).Conclusion: Pre-admission medication adherence is common in patients hospitalized for IHD, regardless of sex. However, patient-related factors such as diabetes, employment, and personality traits are associated with adherence in a sex-specific manner

Premature ovarian insufficiency: From pathogenesis to clinical management

Premature ovarian insufficiency (POI) represents a condition characterized by the absence of normal ovarian function due to an incipient (by 3-10 years) ovarian aging. In most of the women affected there are no signs or symptoms that precede the interruption of menstruation and the onset of POI and the majority of women have a normal history of menarche, regular menstrual cycles and normal fertility. The possible genetic role in the development of POI has been largely demonstrated and many genes have been involved; on the other hand, ovary is not protected immunologically and the detection of autoantibodies directed against various ovarian targets strongly support the hypothesis of an autoimmune etiology. In approximately 5-10% of women with a diagnosis of POI with a normal karyotype, a spontaneous pregnancy could occur even if the recovery of ovarian function is temporary and poorly predictable. Embryo donation and adoption are other alternatives that should be considered. POI and subsequent loss of reproductive capacity is a devastating condition and a difficult diagnosis for women to accept so it requires an individualized and a multidisciplinary approach. Hormonal replacement therapy (HRT) should be commenced as soon as possible to prevent and to contrast the onset of the symptoms related to hypoestrogenism and to improve the quality of life for these women

Understanding Spontaneous Preterm Birth: From Underlying Mechanisms to Predictive and Preventive Interventions

6noreservedPreterm birth is defined as birth before 37 weeks' gestational age. With an incidence of 7% to 11%, it is one of the major causes of perinatal mortality and morbidity. Preterm birth is considered a clinical syndrome, which arises from different pathological processes that activate prematurely one or more components of the mechanisms leading to parturition. The premature activation of labor may be caused by multiple pathological conditions; in particular a deregulation of the immune system and an exaggeration of inflammatory processes represent common central mechanisms. The complex pathogenesis, the main risk factors and the different therapeutic options will be described in the present review. Since its incidence is still increasing in the last decades, the goal is to improve the primary and secondary preventionmixedVoltolini, C.; Torricelli, M.; Conti, N.; Vellucci, F.L.; Severi, F.M.; Petraglia, F.Voltolini, C.; Torricelli, M.; Conti, N.; Vellucci, F. L.; Severi, F. M.; Petraglia, F

Histologic chorioamnionitis: different histologic features at different gestational ages

The aim of this study was to investigate the rate of the different histological chorioamnionitis (HCA) grade in relation to the gestational age in term and preterm delivery

Follicular Fluid Components in Reduced Ovarian Reserve, Endometriosis, and Idiopathic Infertility

Follicular fluid (FF) molecules, and their increase or decrease, can contribute to appropriate follicular growth and oocyte maturation, thus being related to female infertility conditions. In this paper, we studied the changes and the relationships of some biochemical components, hormones, antioxidant enzymes, F2-Isoprostanes (F2-IsoPs), and resolvin (Rv) D1 in the FF of infertile women with different reproductive conditions such as endometriosis, reduced ovarian reserve, and idiopathic infertility during assisted reproductive techniques (ART). In the whole population, positive correlations between albumin (ALB)/iron (Fe), ALB/beta-2-microglobulin (B2MG), and F2-IsoPs/RvD1 were detected in the FF. In FF from aged women, increased levels of follicle stimulating hormone (FSH) and reduced anti-M&uuml;llerian hormone (AMH) levels were associated with a worse oocyte quality. The negative ART outcome was influenced by patient age and AMH, B2MG, and FSH levels. Moreover, the reduced ovarian reserve condition was characterised by a significant decrease in oocyte number and quality, AMH amount, and lactate dehydrogenase (LDH) activity, as well as by an increase in age and FSH levels. In the presence of endometriosis, high levels of MDA and RvD1 were detected in FF, with a decrease in luteinising hormone (LH). Finally, among the molecules examined, none characterised the condition of idiopathic infertility. These data could support the identification of new FF markers in different reproductive disorders, suggesting the need for personalised therapeutic approaches and optimised ART outcomes. In particular, the evaluation of resolvins and lipid mediators in FF could be a promising field of investigation with which to understand the entity of oxidative stress and inflammation in some female infertility conditions

Follicular Fluid Components in Reduced Ovarian Reserve, Endometriosis, and Idiopathic Infertility

Follicular fluid (FF) molecules, and their increase or decrease, can contribute to appropriate follicular growth and oocyte maturation, thus being related to female infertility conditions. In this paper, we studied the changes and the relationships of some biochemical components, hormones, antioxidant enzymes, F2-Isoprostanes (F2-IsoPs), and resolvin (Rv) D1 in the FF of infertile women with different reproductive conditions such as endometriosis, reduced ovarian reserve, and idiopathic infertility during assisted reproductive techniques (ART). In the whole population, positive correlations between albumin (ALB)/iron (Fe), ALB/beta-2-microglobulin (B2MG), and F2-IsoPs/RvD1 were detected in the FF. In FF from aged women, increased levels of follicle stimulating hormone (FSH) and reduced anti-Müllerian hormone (AMH) levels were associated with a worse oocyte quality. The negative ART outcome was influenced by patient age and AMH, B2MG, and FSH levels. Moreover, the reduced ovarian reserve condition was characterised by a significant decrease in oocyte number and quality, AMH amount, and lactate dehydrogenase (LDH) activity, as well as by an increase in age and FSH levels. In the presence of endometriosis, high levels of MDA and RvD1 were detected in FF, with a decrease in luteinising hormone (LH). Finally, among the molecules examined, none characterised the condition of idiopathic infertility. These data could support the identification of new FF markers in different reproductive disorders, suggesting the need for personalised therapeutic approaches and optimised ART outcomes. In particular, the evaluation of resolvins and lipid mediators in FF could be a promising field of investigation with which to understand the entity of oxidative stress and inflammation in some female infertility conditions