Silent spontaneous uterine rupture in a term pregnancy with extrusion of an intact amniotic sac and without maternal and neonatal morbidity and mortality

Background. Uterine rupture in pregnancy is a rare and catastrophic complication with a high incidence of fetal and maternal morbidity and mortality. Silent spontaneous uterine rupture without maternal or neonatal morbidity or mortality is very rare. Case presentation. We describe a case of silent spontaneous uterine rupture diagnosed during a planned cesarean section in a patient at 38+4 weeks’ gestation with two previous cesarean sections. The mother and newborn were discharged three days later in good health and without complications. Conclusions. Worldwide, the frequency of cesarean deliveries has increased in recent decades and uterine rupture is a very rare catastrophic emergency that can have dramatic consequences. Our case report shows that uterine rupture can occur in pregnancy before labour without any signs or symptoms. Despite the uterine rupture with extrusion of the intact amniotic sac, there were no complications for the mother or the foetus. Timely diagnosis is crucial and future research should find more reproducible parameters to objectify the risk of silent uterine rupture and define the timing of delivery of previous cesarean sections requiring a new surgical delivery. All patients with previous cesarean sections should be counselled about the possibility of early delivery by cesarean section

Diagnostic accuracy of prenatal ultrasound in identifying the level of the lesion in fetuses with open spina bifida: a systematic review and meta-analysis.

INTRODUCTION: The role of prenatal ultrasound in correctly identifying the level of the lesion in fetuses with open spina bifida has yet to be determined. The primary aim of this systematic review was to report the diagnostic accuracy of ultrasound in determining the level of the lesion in fetuses with open spina bifida. The secondary aim was to elucidate whether prenatal magnetic resonance imaging (MRI) improves the diagnostic performance of prenatal imaging in correctly identifying the level of the lesion. MATERIAL AND METHODS: Inclusion criteria were studies reporting the agreement between ultrasound, MRI and postnatal or post-mortem assessment of fetuses with spina bifida. Agreement was defined as: complete (when the upper level of the lesion detected prenatally was the same recorded at postnatal or post-mortem evaluation), within one (when the upper level of the lesion recorded prenatally was within one vertebral body higher or lower than that reported postnatally) and within two vertebral bodies (when the upper level of the lesion recorded prenatally was within two vertebral bodies higher or lower than that reported postnatally or postmortem evaluation). Meta-analyses of proportions were used to combine data. RESULTS: Fourteen studies (655 fetuses) were included. Ultrasound was able to identify the correct level of the lesion in 40.9% (95% CI 26.9-55.6) of cases. The upper level of the lesion recorded on ultrasound was within one vertebral body in 76.2% (95% CI 65.0-85.9) of cases, while within two segments in 92.4% (95% CI 84.3-97.7). Fetal MRI detected the exact level of the lesion in 42.5% (95% CI 35.9-45.2) of cases; the level of the lesion recorded on MRI was higher in 26.4% (95% CI 20.0-33.3) of cases and lower in 32.4% (95% CI 25.5-39.7) than that confirmed postnatally. The upper level of the lesion recorded on MRI was within one vertebral body in 76.2% (95% CI 65.9-85.2) of cases, while within two segments in 94.2% (95% CI 90.2-97.2). CONCLUSIONS: Both ultrasound and MRI have a moderate diagnostic accuracy in identify the upper level of the lesion in fetuses with open spina bifida

An Extended Gene Protein/Products Boolean Network Model Including Post-Transcriptional Regulation

Background: Networks Biology allows the study of complex interactions between biological systems using formal, well structured, and computationally friendly models. Several different network models can be created, depending on the type of interactions that need to be investigated. Gene Regulatory Networks (GRN) are an effective model commonly used to study the complex regulatory mechanisms of a cell. Unfortunately, given their intrinsic complexity and non discrete nature, the computational study of realistic-sized complex GRNs requires some abstractions. Boolean Networks (BNs), for example, are a reliable model that can be used to represent networks where the possible state of a node is a boolean value (0 or 1). Despite this strong simplification, BNs have been used to study both structural and dynamic properties of real as well as randomly generated GRNs. Results: In this paper we show how it is possible to include the post-transcriptional regulation mechanism (a key process mediated by small non-coding RNA molecules like the miRNAs) into the BN model of a GRN. The enhanced BN model is implemented in a software toolkit (EBNT) that allows to analyze boolean GRNs from both a structural and a dynamic point of view. The open-source toolkit is compatible with available visualization tools like Cytoscape and allows to run detailed analysis of the network topology as well as of its attractors, trajectories, and state-space. In the paper, a small GRN built around the mTOR gene is used to demonstrate the main capabilities of the toolkit. Conclusions: The extended model proposed in this paper opens new opportunities in the study of gene regulation. Several of the successful researches done with the support of BN to understand high-level characteristics of regulatory networks, can now be improved to better understand the role of post-transcriptional regulation for example as a network-wide noise-reduction or stabilization mechanism

Risk Factors Associated with Adverse Fetal Outcomes in Pregnancies Affected by Coronavirus Disease 2019 (COVID-19): A Secondary Analysis of the WAPM study on COVID-19

To evaluate the strength of association between maternal and pregnancy characteristics and the risk of adverse perinatal outcomes in pregnancies with laboratory confirmed COVID-19. Secondary analysis of a multinational, cohort study on all consecutive pregnant women with laboratory-confirmed COVID-19 from February 1, 2020 to April 30, 2020 from 73 centers from 22 different countries. A confirmed case of COVID-19 was defined as a positive result on real-time reverse-transcriptase-polymerase-chain-reaction (RT-PCR) assay of nasal and pharyngeal swab specimens. The primary outcome was a composite adverse fetal outcome, defined as the presence of either abortion (pregnancy loss before 22 weeks of gestations), stillbirth (intrauterine fetal death after 22 weeks of gestation), neonatal death (death of a live-born infant within the first 28 days of life), and perinatal death (either stillbirth or neonatal death). Logistic regression analysis was performed to evaluate parameters independently associated with the primary outcome. Logistic regression was reported as odds ratio (OR) with 95% confidence interval (CI). Mean gestational age at diagnosis was 30.6\ub19.5 weeks, with 8.0% of women being diagnosed in the first, 22.2% in the second and 69.8% in the third trimester of pregnancy. There were six miscarriage (2.3%), six intrauterine device (IUD) (2.3) and 5 (2.0%) neonatal deaths, with an overall rate of perinatal death of 4.2% (11/265), thus resulting into 17 cases experiencing and 226 not experiencing composite adverse fetal outcome. Neither stillbirths nor neonatal deaths had congenital anomalies found at antenatal or postnatal evaluation. Furthermore, none of the cases experiencing IUD had signs of impending demise at arterial or venous Doppler. Neonatal deaths were all considered as prematurity-related adverse events. Of the 250 live-born neonates, one (0.4%) was found positive at RT-PCR pharyngeal swabs performed after delivery. The mother was tested positive during the third trimester of pregnancy. The newborn was asymptomatic and had negative RT-PCR test after 14 days of life. At logistic regression analysis, gestational age at diagnosis (OR: 0.85, 95% CI 0.8-0.9 per week increase; p<0.001), birthweight (OR: 1.17, 95% CI 1.09-1.12.7 per 100 g decrease; p=0.012) and maternal ventilatory support, including either need for oxygen or CPAP (OR: 4.12, 95% CI 2.3-7.9; p=0.001) were independently associated with composite adverse fetal outcome. Early gestational age at infection, maternal ventilatory supports and low birthweight are the main determinants of adverse perinatal outcomes in fetuses with maternal COVID-19 infection. Conversely, the risk of vertical transmission seems negligible

Echography and cytology in the study of spreading pathology of the salivary glands

The contribution of the combined use of US and cytology is evaluated in the diagnosis of masses in the salivary glands and adjacent structures. US had 87.2% sensitivity in locating the mass; its accuracy in defining both physical structure and benign/malignant nature of the lesion was 91% and 74%, respectively. Thus US, after demonstrating a lesion, does not always allow the exact definition of its characteristic. In many of these cases, other imaging modalities do not help either. In our series of cases, cytology allowed an unquestionable diagnosis to be made in 87.2% of cases, and the combined use of US and cytology rose the figure to 97%. The only limitation is the evaluation of the deep extent of large masses: in such cases CT or, if available, MR imaging are recommended

Diagnostic accuracy of prenatal ultrasound in identifying the level of the lesion in fetuses with open spina bifida: A systematic review and meta-analysis

none10siIntroduction: The role of prenatal ultrasound in correctly identifying the level of the lesion in fetuses with open spina bifida has yet to be determined. The primary aim of this systematic review was to&nbsp;report the diagnostic accuracy of ultrasound in determining the level of the lesion in fetuses with open spina bifida. The secondary aim was to elucidate whether prenatal magnetic resonance imaging (MRI) improves the diagnostic performance of prenatal imaging in correctly identifying the level of the lesion. Material and methods: Inclusion criteria were studies reporting the agreement between ultrasound, MRI and postnatal or postmortem assessment of fetuses with spina bifida. Agreement was defined as: complete (when the upper level of the lesion detected prenatally was the same recorded at postnatal or postmortem evaluation), within one (when the upper level of the lesion recorded prenatally was within one vertebral body higher or lower than that reported postnatally) and within two vertebral bodies (when the upper level of the lesion recorded prenatally was within two vertebral bodies higher or lower than that reported postnatally or postmortem evaluation). Meta-analyses of proportions were used to combine data. Results: Fourteen studies (655 fetuses) were included. Ultrasound was able to identify the correct level of the lesion in 40.9% (95% confidence interval [CI] 26.9-55.6) of cases. The upper level of the lesion recorded on ultrasound was within one vertebral body in 76.2% (95% CI 65.0-85.9) of cases and within two segments in 92.4% (95% CI 84.3-97.7). Fetal MRI detected the exact level of the lesion in 42.5% (95% CI 35.9-45.2) of cases; the level of the lesion recorded on MRI was higher in 26.4% (95% CI 20.0-33.3) of cases and lower in 32.4% (95% CI 25.5-39.7) than that confirmed postnatally. The upper level of the lesion recorded on MRI was within one vertebral body in 76.2% (95% CI 65.9-85.2) of cases and within two segments in 94.2% (95% CI 90.2-97.2). Conclusions: Both ultrasound and MRI have a moderate diagnostic accuracy in identify the upper level of the lesion in fetuses with open spina bifida.embargoed_20210926Di Mascio D.; Greco F.; Rizzo G.; Khalil A.; Buca D.; Sorrentino F.; Vasciaveo L.; Greco P.; Nappi L.; D'Antonio F.Di Mascio, D.; Greco, F.; Rizzo, G.; Khalil, A.; Buca, D.; Sorrentino, F.; Vasciaveo, L.; Greco, P.; Nappi, L.; D'Antonio, F

NSD2 maintains lineage plasticity and castration-resistance in neuroendocrine prostate cancer.

The clinical use of potent androgen receptor (AR) inhibitors has promoted the emergence of novel subtypes of metastatic castration-resistant prostate cancer (mCRPC), including neuroendocrine prostate cancer (CRPC-NE), which is highly aggressive and lethal 1 . These mCRPC subtypes display increased lineage plasticity and often lack AR expression 2-5 . Here we show that neuroendocrine differentiation and castration-resistance in CRPC-NE are maintained by the activity of Nuclear Receptor Binding SET Domain Protein 2 (NSD2) 6 , which catalyzes histone H3 lysine 36 dimethylation (H3K36me2). We find that organoid lines established from genetically-engineered mice 7 recapitulate key features of human CRPC-NE, and can display transdifferentiation to neuroendocrine states in culture. CRPC-NE organoids express elevated levels of NSD2 and H3K36me2 marks, but relatively low levels of H3K27me3, consistent with antagonism of EZH2 activity by H3K36me2. Human CRPC-NE but not primary NEPC tumors expresses high levels of NSD2, consistent with a key role for NSD2 in lineage plasticity, and high NSD2 expression in mCRPC correlates with poor survival outcomes. Notably, CRISPR/Cas9 targeting of NSD2 or expression of a dominant-negative oncohistone H3.3K36M mutant results in loss of neuroendocrine phenotypes and restores responsiveness to the AR inhibitor enzalutamide in mouse and human CRPC-NE organoids and grafts. Our findings indicate that NSD2 inhibition can reverse lineage plasticity and castration-resistance, and provide a potential new therapeutic target for CRPC-NE