Salvatore Andrea Mastrolia

Disseminated intravascular coagulation in pregnancy: insights in pathophysiology, diagnosis and management

Disseminated intravascular coagulation (DIC) is a life-threatening situation that can arise from a variety of obstetrical and nonobstetrical causes. Obstetrical DIC has been associated with a series of pregnancy complications including the following: (1) acute peripartum hemorrhage (uterine atony, cervical and vaginal lacerations, and uterine rupture); (2) placental abruption; (3) preeclampsia/eclampsia/hemolysis, elevated liver enzymes, and low platelet count syndrome; (4) retained stillbirth; (5) septic abortion and intrauterine infection; (6) amniotic fluid embolism; and (7) acute fatty liver of pregnancy. Prompt diagnosis and understanding of the underlying mechanisms of disease leading to this complication in essential for a favorable outcome. In recent years, novel diagnostic scores and treatment modalities along with bedside point-of-care tests were developed and may assist the clinician in the diagnosis and management of DIC. Team work and prompt treatment are essential for the successful management of patients with DIC.

Risk of long-term pelvic recurrences after fluid minihysteroscopy in women with endometrial carcinoma: a controlled randomized study.

Objective: Concerns exist about the risk of endometrial cancer cells spreading into the peritoneal cavity after fluid minihysteroscopy. The aim of our study was to evaluate the 5-year incidence of pelvic recurrences in women affected by early-stage endometrial carcinoma (stage IA or IB) who did or did not undergo preoperative hysteroscopy with low pressure (<70 mm Hg) saline uterine distention. Methods: A total of 140 women were randomized into two groups of 70 women who underwent or did not undergo diagnostic fluid minihysteroscopy before surgical staging. Women were followed up every 6 months for at least 5 years. Diagnosis of pelvic recurrence was based on a positive result at clinical examination and/or at vaginal cytology and/or at magnetic resonance imaging/positron emission tomography scan. Univariate analysis of disease-free survival was performed with the Kaplan-Meier method and survival curves were compared using the long-rank test. Results: No difference in peritoneal cytology was observed between the two groups (5.7% and 8.5% of cases in the hysteroscopy and control group, respectively). After a mean duration of follow-up of 62 months, 2 (2.85%) pelvic recurrences in the hysteroscopy group and 3 (4.28%) in the control group were found. No significant difference was found between the two groups when the recurrence rate was compared. Overall survival rates and disease-free survival projected by Kaplan-Meier curves were not significantly different for the two groups. Conclusions: Preoperative low-pressure fluid minihysteroscopy does not increase the risk of intraperitoneal transport of endometrial carcinoma cells during the examination or the risk of pelvic recurrence at the 5-year follow-up. It does not seem to modify the recurrence rate, disease-free survival, and overall survival, although multicenter randomized trials and long-term follow-up are required to evaluate the overall oncologic outcomes of this procedure.

The physiologic and therapeutic role of heparin in implantation and placentation.

Implantation, trophoblast development and placentation are crucial processes in the establishment and development of normal pregnancy. Abnormalities of these processes can lead to pregnancy complications known as the great obstetrical syndromes: preeclampsia, intrauterine growth restriction, fetal demise, premature prelabor rupture of membranes, preterm labor, and recurrent pregnancy loss. There is mounting evidence regarding the physiological and therapeutic role of heparins in the establishment of normal gestation and as a modality for treatment and prevention of pregnancy complications. In this review, we will summarize the properties and the physiological contributions of heparins to the success of implantation, placentation and normal pregnancy.

Galectins: Double-edged Swords in the Cross-roads of Pregnancy Complications and Female Reproductive Tract Inflammation and Neoplasia.

Galectins are an evolutionarily ancient and widely expressed family of lectins that have unique glycan-binding characteristics. They are pleiotropic regulators of key biological processes, such as cell growth, proliferation, differentiation, apoptosis, signal transduction, and pre-mRNA splicing, as well as homo- and heterotypic cell-cell and cell-extracellular matrix interactions. Galectins are also pivotal in immune responses since they regulate host-pathogen interactions, innate and adaptive immune responses, acute and chronic inflammation, and immune tolerance. Some galectins are also central to the regulation of angiogenesis, cell migration and invasion. Expression and functional data provide convincing evidence that, due to these functions, galectins play key roles in shared and unique pathways of normal embryonic and placental development as well as oncodevelopmental processes in tumorigenesis. Therefore, galectins may sometimes act as double-edged swords since they have beneficial but also harmful effects for the organism. Recent advances facilitate the use of galectins as biomarkers in obstetrical syndromes and in various malignancies, and their therapeutic applications are also under investigation. This review provides a general overview of galectins and a focused review of this lectin subfamily in the context of inflammation, infection and tumors of the female reproductive tract as well as in normal pregnancies and those complicated by the great obstetrical syndromes.

Reliability of narrow-band imaging (NBI) hysteroscopy: a comparative study.

OBJECTIVE To evaluate the usefulness of narrow-band imaging (NBI) technology for improving the diagnostic reliability of hysteroscopy. DESIGN Prospective controlled clinical study (Canadian Task Force classification II-2). SETTING University hospital. PATIENT(S) Three hundred ninety-five outpatient women undergoing diagnostic hysteroscopy were enrolled. INTERVENTION(S) All patients underwent fluid minihysteroscopy with white light (WL) and NBI exploration with endometrial eye-directed biopsy. MAIN OUTCOME MEASURE(S) Hysteroscopic findings with WL and NBI were compared with histology, which was considered the gold standard. RESULT(S) Overall, the number of correct diagnoses with NBI was significantly higher than with WL. For differentiating normal from abnormal endometrial histopathology, the use of NBI showed a significantly higher specificity (0.93 vs. 0.78) and negative predictive value (0.92 vs. 0.81); NBI hysteroscopy significantly improved the sensitivity for the diagnosis of proliferative endometrium (0.93 vs. 0.78), chronic endometritis (0.88 vs. 0.70), low-risk hyperplasia (0.88 vs. 0.70), and high-risk hyperplasia (0.60 vs. 0.40). CONCLUSION(S) The use of NBI improved the reliability of diagnostic hysteroscopy. The high specificity and the low number of false negatives may reduce the number of unnecessary biopsies or of those performed in wrong areas. Moreover, compared with WL observation, NBI hysteroscopy showed significantly higher sensitivity for the detection of chronic endometritis and low-risk and high-risk hyperplasia.

Epigenetic Matters: The Link between Early Nutrition, Microbiome, and Long-term Health Development

Epigenetic modifications are among the most important mechanisms by which environmental factors can influence early cellular differentiation and create new phenotypic traits during pregnancy and within the neonatal period without altering the deoxyribonucleic acid sequence. A number of antenatal and postnatal factors, such as maternal and neonatal nutrition, pollutant exposure, and the composition of microbiota, contribute to the establishment of epigenetic changes that can not only modulate the individual adaptation to the environment but also have an influence on lifelong health and disease by modifying inflammatory molecular pathways and the immune response. Postnatal intestinal colonization, in turn determined by maternal flora, mode of delivery, early skin-to-skin contact and neonatal diet, leads to specific epigenetic signatures that can affect the barrier properties of gut mucosa and their protective role against later insults, thus potentially predisposing to the development of late-onset inflammatory diseases. The aim of this review is to outline the epigenetic mechanisms of programming and development acting within early-life stages and to examine in detail the role of maternal and neonatal nutrition, microbiota composition, and other environmental factors in determining epigenetic changes and their short- and long-term effects.

A prior placenta accreta is an independent risk factor for post-partum hemorrhage in subsequent gestations

OBJECTIVE The rate of placenta accreta, a life threatening condition, is constantly increasing, mainly due to the rise in the rates of cesarean sections. This study is aimed to determine the effect of a history of placenta accreta on subsequent pregnancies. STUDY DESIGN A population based retrospective cohort study was designed, including all women who delivered at our medical center during the study period. The study population was divided into two groups including pregnancies with: (1) a history of placenta accreta (n=514); and (2) control group without placenta accreta (n=239,126). RESULTS (1) A history of placenta accreta is an independent risk factor for postpartum hemorrhage (adjusted OR 4.1, 95% CI 1.5-11.5) as were placenta accreta (adjusted OR 22.0, 95% CI 14.0-36.0) and placenta previa (adjusted OR 7.6, 95% CI 4.4-13.2) in the current pregnancy, and a prior cesarean section (adjusted OR 1.7, 95% CI 1.3-2.2); (2) in addition, placenta accreta in a previous pregnancy is associated with a reduced rate of mild preeclampsia in future pregnancies (1.8% vs. 3.4%, RR 0.51, 95% CI 0.26-0.98); (3) however, in spite of the higher rate of neonatal deaths in the study group, a history of placenta accreta was not an independent risk factor for total perinatal mortality (adjusted OR 1.0, 95% CI 0.5-1.9) after adjusting for confounders. CONCLUSION A history of placenta accreta is an independent risk factor for postpartum hemorrhage. This should be taken into account in order to ensure a safety pregnancy and delivery of these patients.

Cerebral Palsy-Trends in Epidemiology and Recent Development in Prenatal Mechanisms of Disease, Treatment, and Prevention.

Cerebral palsy (CP) is the most common motor disability in childhood. This syndrome is the manifestation of intrauterine pathologies, intrapartum complications, and the postnatal sequel, especially among preterm neonates. A double hit model theory is proposed suggesting that an intrauterine condition along with intrapartum or postnatal insult lead to the development of CP. Recent reports demonstrated that treatment during the process of preterm birth such as magnesium sulfate and postnatal modalities such as cooling may prevent or reduce the prevalence of this syndrome. Moreover, animal models demonstrated that postnatal treatment with anti-inflammatory drugs coupled with nanoparticles may affect the course of the disease in pups with neuroinflammation. This review will describe the changes in the epidemiology of this disease, the underlying prenatal mechanisms, and possible treatments that may reduce the prevalence of CP and alter the course of the disease.

The physiologic anticoagulant and anti-inflammatory role of heparins and their utility in the prevention of pregnancy complications

Accumulating evidence supports the concept of increased thrombin generation, placental vascular lesions, and inflammation as crucial points in the development of the great obstetrical syndromes [preeclampsia, intrauterine growth restriction (IUGR), preterm labor (PTL), preterm prelabor rupture of membranes (PROM), fetal demise and recurrent abortions]. In light of this, the role of heparins for primary or secondary prevention of these syndromes is becoming more and more apparent, mainly due to the antithrombotic and anti-inflammatory effects of heparins. There is agreement regarding the use of heparin in the prevention of gestational complications in patients with antiphospholipid syndrome, while its use for other obstetrical complications is under debate. In the present review we will describe the physiologic role of heparins on coagulation and inflammation and we will discuss current evidence regarding the use of heparins for the prevention/treatment of obstetrical syndromes.

Umbilical artery blood flows among pregnancies with single umbilical artery: a prospective case-control study

Abstract Objectives: To evaluate peak systolic velocity (PSV) in the umbilical artery (UA) among patients with single umbilical artery (SUA) as compared with patients with three vessel cords. Methods: A prospective case-control study was performed. UA blood flow velocimetry was obtained from fetuses with SUA and from a control group with three vessel cord. PSV and pulsatility index (PI) were measured. Patients’ characteristics were compared for statistical differences and a linear regression model was constructed for the different groups. Results: UA Doppler velocimetry measurements were obtained from 29 patients with SUA and from 29 controls matched for gestational age. The differences between UA PI with and without SUA were significant (F = 3.471; p = 0.0379) showing a lower PI in the SUA group. However, no significant statistical difference was found in PSV between these two groups (F = 0.149; p = 0.86). Conclusions: While the impedance in the UA of patients with a SUA was lower compared with patients with a normal umbilical cord, the PSV did not differ.