Could molecular assessment of calcium metabolism be a useful tool to early screen patients at risk for pre-eclampsia complicated pregnancy? Proposal and rationale.

Abstract One of the most frequent causes of maternal and perinatal morbidity is represented by hypertensive disorders during pregnancy. Women at high risk must be subjected to a more intensive antenatal surveillance and prophylactic treatments. Many genetic risk factors, clinical features and biomarkers have been proposed but none of these seems able to prevent pre-eclampsia onset. English literature review of manuscripts focused on calcium intake and hypertensive disorders during pregnancy was performed. We performed a critical analysis of evidences about maternal calcium metabolism pattern in pregnancy analyzing all possible bias affecting studies. Calcium supplementation seems to give beneficial effects on women with low calcium intake. Some evidence reported that calcium supplementation may drastically reduce the percentage of pre-eclampsia onset consequently improving the neonatal outcome. Starting from this evidence, it is intuitive that investigations on maternal calcium metabolism pattern in first trimester of pregnancy could represent a low cost, large scale tool to screen pregnant women and to identify those at increased risk of pre-eclampsia onset. We propose a biochemical screening of maternal calcium metabolism pattern in first trimester of pregnancy to discriminate patients who potentially may benefit from calcium supplementation. In a second step we propose to randomly allocate the sub-cohort of patients with calcium metabolism disorders in a treatment group (calcium supplementation) or in a control group (placebo) to define if calcium supplementation may represent a dietary mean to reduce pre-eclampsia onset and to improve pregnancy outcome

2022-RA-1401-ESGO Comparison of ADNEXmodel, O-RADSand the combinedIOTA simple rules with simple rules risk assessment and simple rules with ADNEX model in discriminating between benign and malignant adnexalmasses

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Integra® dermal matrix bioengineered with platelet rich plasma (PRP) and mesenchymal stromal cells to serve as niche for skin regeneration

Regenerative medicine strategies represent one of the main challenges to improve tissue healing and repair after damage or chronic pathologies. In this perspective, the setting of bioengineered scaffolds, namely synthetic matrices enriched with growth factors and stem cells, is considered a hot issue by numerous research groups. In a previous “in vitro” study we have demonstrated that rat bone marrow-derived mesenchymal stem cells (MSCs) seeded on an artificial dermal matrix Integra®, enriched with platelet-rich plasma (PRP) displayed enhanced proliferative attitude as compared with those cultured in the presence of PRP or on the scaffold alone. To this purpose, in this study we wanted to extend the experimentation by evaluating the efficacy of the bioengineered Integra® in an in vivo model of skin damage in rats. In particular, we used MSC derived from genetically modified rats overexpressing green fluorescent protein (GFP). Rats were divided into different groups: those receiving Integra® or PRP alone, Integra® plus PRP, Integra® plus PRP and MSC, and injured and untreated rats. Skin biopsies, obtained at different times from the injury and the implant, were examined to evaluate the regeneration process and neovascularization pattern of the substrate at light an confocal immunofluorescence microscopy. In parallel experiments we evaluated the ability of MSC to release growth factors, namely VEGF and FGF, and immunomodulatory cytokines, to underscore the paracrine effects of these cells on the surrounding host tissue

Endometrial scratch injury before intrauterine insemination: is it time to re-evaluate its value? Evidence from a systematic review and meta-analysis of randomized controlled trials

OBJECTIVE: To assess the impact of endometrial scratch injury (ESI) on the outcomes of intrauterine insemination (IUI) stimulated cycles. DESIGN: Systematic review and meta-analysis. SETTING: Not applicable. PATIENT(S): Infertile women undergoing one or more IUI stimulated cycles. INTERVENTION(S): Randomized controlled trials (RCTs) were identified by searching electronic databases. We included RCTs comparing ESI (i.e., intervention group) during the course of IUI stimulated cycle (C-ESI) or during the menstrual cycle preceding IUI treatment (P-ESI) with controls (no endometrial scratch). The summary measures were reported as odds ratio (OR) with 95% confidence-interval (CI). MAIN OUTCOME MEASURE(S): Clinical pregnancy rate, ongoing pregnancy rate, multiple pregnancy rate, ectopic pregnancy rate, miscarriage rate. RESULT(S): Eight trials were included in the meta-analysis, comprising a total of 1,871 IUI cycles. Endometrial scratch injury was associated with a higher clinical pregnancy rate (OR 2.27) and ongoing pregnancy rate (OR 2.04) in comparison with the controls. No higher risk of multiple pregnancy (OR 1.09), miscarriage (OR 0.80), or ectopic pregnancy (OR 0.82) was observed in patients receiving ESI. Subgroup analysis based on ESI timing showed higher clinical pregnancy rate (OR 2.57) and ongoing pregnancy rate (OR 2.27) in patients receiving C-ESI and no advantage in patients receiving P-ESI. CONCLUSION(S): Available data suggest that ESI performed once, preferably during the follicular phase of the same cycle of IUI with flexible aspiration catheters, may improve clinical pregnancy and ongoing pregnancy rates in IUI cycles. Endometrial scratch injury does not appear to increase the risk of multiple pregnancy, miscarriage, or ectopic pregnancy

Uterine fibroid size modifications during pregnancy and puerperium: evidence from the first systematic review of literature

PURPOSE: The influence of pregnancy on uterine fibroid size still remains an unsolved dilemma. Basing on current knowledge, physicians are not able to inform patients about the likelihood of uterine fibroids to modify their size during pregnancy. Study aim was to summarize available evidence concerning the size modifications of uterine fibroids during each trimester of pregnancy and during puerperium. METHODS: The review was reported following the PRISMA guidelines and registered in PROSPERO (registration number: CRD42017071117). A literature search was conducted in electronic database (PubMed, Embase, Sciencedirect, the Cochrane library and Clinicaltrials.gov) until July 2017. All studies evaluating fibroids' changes during pregnancy and puerperium by ultrasound or magnetic-resonance-imaging were included. Descriptive characteristics of studies and patients were collected. The modifications of uterine fibroid diameter and volume were the outcome measures. RESULTS: Concerning the first trimester of pregnancy, all authors reported a significant growth of uterine fibroids. Contradictory evidence was found about uterine fibroid modifications during the second and third trimesters, mainly supporting a slowdown during mid pregnancy and a subsequent size reduction during late pregnancy. Concerning the overall modifications during pregnancy and puerperium, poor evidence quality suggests that uterine fibroids do not modify their volume/slightly enlarge during pregnancy and subsequently reduce in size during puerperium. CONCLUSIONS: Uterine fibroids seem to be subject to a non-linear trend of modifications during pregnancy and puerperium, which may vary from myoma to myoma. Adequate evidence supports uterine fibroid systematic enlargement during the first trimester of pregnancy, while inconsistent evidence is available about the changes of uterine fibroids during second and third trimesters. In addition, the overall modifications of myomas during pregnancy and puerperium remain unclear

Efficacy and Safety of Alemtuzumab Through 9 Years of Follow-up in Patients with Highly Active Disease: Post Hoc Analysis of CARE-MS I and II Patients in the TOPAZ Extension Study

Background: Alemtuzumab efficacy versus subcutaneous interferon-β-1a (SC IFNB-1a) was demonstrated over 2 years in patients with relapsing-remitting multiple sclerosis, with continued efficacy over 7 additional years. Alemtuzumab is included as a recommended treatment for patients with highly active disease (HAD) by the American Academy of Neurology Practice Guidelines, and the label indication in Europe was recently restricted to the treatment of HAD patients. There is currently no consensus definition for HAD, and alemtuzumab efficacy across various HAD definitions has not been explored previously. Objectives: In this post hoc analysis, we assess the efficacy and safety of alemtuzumab in Comparison of Alemtuzumab and Rebif® Efficacy in Multiple Sclerosis (CARE-MS) trial patients who met criteria for at least one of four separate definitions of HAD (one primary and three alternatives). Over 2 years, alemtuzumab-treated HAD patients were compared with SC IFNB-1a-treated HAD patients, with additional 7-year follow-up in patients from the alemtuzumab arm. Methods: Patients in the CARE-MS studies received either alemtuzumab (baseline: 5 days; 12 months later: 3 days) or SC IFNB-1a (3 times weekly). Alemtuzumab-treated patients who enrolled in the extensions could receive additional courses ≥ 12 months apart. Four definitions of HAD were applied to assess alemtuzumab efficacy: the pre-specified primary definition (two or more relapses in the year prior to baseline and at least one gadolinium [Gd]-enhancing lesion at baseline) and three alternative definitions that focused on relapse, magnetic resonance imaging (MRI), or prior treatment response criteria. Efficacy outcomes were annualized relapse rate, change in Expanded Disability Status Scale score, 6-month confirmed disability worsening, 6-month confirmed disability improvement, MRI disease activity, and brain volume change. Adverse events were summarized for HAD patients meeting the primary definition. Results: In the pooled CARE-MS population, 208 alemtuzumab-treated patients met the primary HAD definition. Annualized relapse rate was 0.27 in years 0–2 and 0.16 in years 3–9. Over 9 years, 62% of patients were free of 6-month confirmed disability worsening, 50% had 6-month confirmed disability improvement, and median cumulative change in brain volume was − 2.15%. During year 9, 62% had no evidence of disease activity, and 69% were free of MRI disease activity. Similar efficacy outcomes were observed using an alternative relapse-driven HAD definition. For patients meeting alternative HAD definitions focused on either higher MRI lesion counts or disease activity while on prior therapy, reduced efficacy for some endpoints was seen. Safety was consistent with the overall CARE-MS population through year 9. Conclusions: Over 9 years, alemtuzumab efficacy was maintained in CARE-MS HAD patients based on four HAD definitions. These results support intervention with alemtuzumab in patients with early indicators of HAD, including frequent relapse without high MRI activity. No safety signals were observed over 9 years that were unique to the HAD populations. ClinicalTrials.gov Identifiers: NCT00530348; NCT00548405; NCT00930553; NCT02255656

Expression, localization and clinical-pathological correlation of maspin (mammary serine protease inhibitor) in endometrial carcinoma

INTRODUZIONE: La maspina è una proteina appartenente alla famiglia delle serpine, la cui espressione è alterata nei tumori di vari organi e tessuti. Anche nel carcinoma endometriale è presente la maspina, ma non è chiaro se esista una relazione tra la sua presenza, concentrazione e localizzazione intracellulare e l’aggressività tumorale. Scopo di questo studio è stato quello di analizzare l’espressione della maspina nell’adenocarcinoma endometriale, e valutare se tale proteina possa essere utile come indicatore di aggressività tumorale, correlandone l’espressione con un marcatore di proliferazione cellulare (KI-67) e con la p53 MATERIALI E METODI: L’espressione della maspina, della p53 e del KI-67 è stata valutata mediante tecnica immunoistochimica su preparati istologici relativi a 107 casi di adenocarcinoma endometriale, a 76 casi con evidenza istologica di iperplasia endometriale tipica o atipica e 24 casi di endometrio normale. L’espressione delle tre proteine è stata correlata tra i diversi gruppi, e, nei casi di adenocarcinoma endometriale, con il grado di differenziazione istologica e con lo stadio FIGO 2009. RISULTATI: Non è stata osservata espressione della maspina nel tessuto endometriale normale e in percentuale molto bassa (14.3%) nei casi di iperplasia endometriale tipica. Molti casi di iperplasia endometriale atipica e di adenocarcinoma endometriale, invece, sono risultati positivi (rispettivamente il 45% e il 48.6%), ma non si sono evidenziate correlazioni significative tra l’espressione della maspina e il grado di differenziazione istologico o lo stadio tumorale. Tutti i 9 (17.3%) casi in cui è stata osservata l’espressione della maspina a livello nucleare appartenevano all’adenocarcinoma endometriale in stadio IA. Nei casi che esprimevano maspina, non sono emerse associazioni significative tra la percentuale di espressione della maspina e la p53 o la KI-67. CONCLUSIONI: Da questo studio emerge che l’espressione della maspina nelle cellule endometriali correla con l’iperplasia atipica e con l’adenocarcinoma endometriale, e può quindi giocare un ruolo nella trasformazione neoplastica dell’endometrio. La maspina è espressa in maniera significativamente più elevata nell’iperplasia endometriale atipica rispetto a quella tipica, e questo potrebbe rivelarsi un utile ausilio in presenza di quadri anatomo-patologici di dubbia interpretazione. E’ stato confermato inoltre che l’espressione di maspina a livello nucleare correla con bassi stadi di malattia, potendo quindi avere un ruolo nella valutazione della prognosi delle pazienti.INTRODUCTION: Maspin is a member of the serpin family whose expression is altered in tumors of various organs and tissues. In endometrial cancer maspin is present, but it is unclear whether a relationship exists between the presence, percentage and intracellular localization of maspin, and tumor aggressiveness. The purpose of this study was to analyze the expression of maspin in endometrial cancer, and to assess whether this protein may be useful as an indicator of tumor aggressiveness, also correlating the expression of maspin with the expression of a marker of cell proliferation (Ki-67) and p53 MATERIALS AND METHODS: The expression of maspin, p53 and Ki-67 was assessed by immunohistochemical staining on histological preparations of 107 cases of endometrial adenocarcinoma, 76 cases with histological evidence of endometrial typical or atypical hyperplasia, and 24 cases of normal endometrium. The expression of the three proteins was correlated between different groups, and, in cases of endometrial adenocarcinoma, with the grading and FIGO stage RESULTS: There was no expression of maspin in normal endometrial tissue, and very low percentage (14.3%) of expression in cases of typical endometrial hyperplasia. However many cases of atypical endometrial hyperplasia and endometrial adenocarcinoma, were positive (respectively 45% and 48.6%), but there were no significant correlations between expression of maspin and grading or tumor stage. All 9 (17.3%) cases in which was observed nuclear expression of maspin belonged to endometrial adenocarcinoma stage IA. In cases that expressed maspin, there were no significant associations between the percentage of maspin expression, p53 or KI-67. CONCLUSIONS: The expression of maspin in endometrial cells correlates with atypical hyperplasia and endometrial adenocarcinoma, therefore maspin may play a role in neoplastic transformation of the endometrium. The maspin is expressed in a significantly higher percentage in endometrial atypical hyperplasia than typical, and this could be a useful aid in the presence of pathological features of dubious interpretation. This study confirm that the nuclear subcellular localization of maspin correlates with low stages of disease, and could therefore have a role in assessing the prognosis of patient

Bladder endometriosis: A summary of current evidence

Bladder endometriosis is a specific form of endometriosis characterized by the presence of endometrial glands and stroma in the detrusor muscle. Such disease may involve different sites of the bladder, most frequently the base and the dome, with various grade of infiltration. Bladder nodules typically coexists with other localizations of deep pelvic endometriosis, resulting in a wide variety of abdominal and urinary symptoms that may be overlooked by clinicians. In spite of advances in understanding the genetic and molecular development of endometriosis, the clinical approach to bladder lesions is very challenging and may require the use of different diagnostic tools in order to set up a comprehensive diagnostic workup and direct towards the most appropriate treatment. The aim of this paper was to portray the state of art of diagnosis and management of bladder endometriosis, starting from the current evidence about epidemiology, pathophysiology, clinical signs and providing all the available strategies for medical and surgical treatmen