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OBJECTIVE: To assess the efficacy of progestogens for maintenance tocolysis in women undelivered after their first preterm labor episode. METHODS: Women with singleton pregnancies between 22 0/7 and 31 6/7 weeks of gestation with arrested preterm labor and a cervical length 25 mm or less at hospital discharge were eligible. Patients with a previous preterm birth were excluded. In a randomized controlled trial conducted in five university hospitals, women were randomized to receive vaginal progesterone (200 mg per day) or intramuscular 17α-hydroxyprogesterone caproate (341 mg per week) or to an observation groups (control group). The primary outcome was the proportion of women with preterm birth at less than 37 weeks of gestation. A sample size of 160 per group (n=480) was planned to compare vaginal progesterone and 17ahydroxyprogesterone caproate groups with those in the control group. The sample size estimation was based on the hypothesis that the risk of experiencing preterm birth in the control group would be 30% and that 17α-hydroxyprogesterone caproate or progesterone would decrease this risk to 15%. A P value of ≤.025 was defined as statistically significant. At planned interim analysis (n=254), the trial was stopped for futility. RESULTS: Between July 2010 and June 2015, 257 women were eligible and 254 were subsequently randomly assigned to vaginal progesterone (n=86), 17α-hydroxyprogesterone caproate (n=87), or observation (n=81). Nineteen (8%) were excluded from the analysis because they either dropped out or information was missing, leaving 235 women available for analysis. Demographic characteristics were similar across groups. The preterm birth rate did not differ significantly between groups: 23% in the 17a-hydroxyprogesterone caproate group, 39% in the vaginal progesterone group, and 22% in the women in the control group (P=.949 for 17a-hydroxyprogesterone caproate compared with the women in the control group and P=.027 for vaginal progesterone compared with women in the control group). CONCLUSION: The use of progestogens for maintenance tocolysis in women with a short cervix did not reduce the rate of preterm birth.

To report our experience on implementation and preliminary results of a decision-making model based on the recommendations of an Interdisciplinary Oncological Care Group developed for the management of colorectal cancer.The multidisciplinary team identified a reference guideline using appraisal of guidelines for research and evaluation (AGREE) tool based on a sequential assessment of the guideline quality. Thereafter, internal guidelines with diagnostic and therapeutic management for early, locally advanced and metastatic colonic and rectal cancer were drafted; organizational aspects, responsibility matrices, protocol actions for each area of specialty involved and indicators for performing audits were also defined.The National Institute for Health and Care Excellence (NICE) UK guideline was the reference for drafting the internal guideline document; from February to November 2013, 125 patients with colorectal cancer were discussed by and taken under the care of the Interdisciplinary Oncological Care Group. The first audit performed in December 2013 revealed optimal adherence to the internal guideline, mainly in terms of uniformity and accuracy of perioperative staging, coordination and timing of multi-modal therapies. To date, all patients under observation are within the diagnostic and therapeutic course, no patient came out from the multidisciplinary "path" and only in 14% of cases have the first recommendations proposed been changed. The selected indicators appear effective and reliable, while at the moment, it is not yet possible to assess the impact of the multidisciplinary team on clinical outcome.Although having a short observation period, our model seems capable of determining optimal uniformity of diagnostic and therapeutic management, to a high degree of patient satisfaction. A longer observation period is necessary in order to confirm these observations and for assessing the impact on clinical outcome.

To evaluate survival outcomes of patients in pStage II-III rectal cancer treated with adjuvant 5-fluorouracil-based radiochemotherapy and to retrospectively analyze the impact of prognostic variables on local control, metastasis-free survival and cause-specific survival.A total of 1,338 patients, treated between 1985-2005 for locally advanced rectal cancer, who underwent surgery and postoperative 5-fluorouracil-based chemoradiation, were selected.The actuarial 5- and 10-year outcomes were: local control 87.0%-84.1%, disease-free survival 61.6%-52.1%, metastasis-free survival 72.0%-67.2%, cause-specific survival 70.4%-57.5%, and overall survival 63.8%-53.4%. Better outcomes were observed in patients with IIA, IIIA stage. Multivariate analyses showed that variables significantly affecting metastasis-free survival were pT4 and pN2, while for cancer-specific survival those variables were age65 years, pT4, pN1, pN2, distal tumors and number of lymph nodes removed ≤ 12.This study confirmed that among stage II-III rectal cancer patients there are subgroups of patients with different clinical outcomes.

OBJECTIVES: Monoamniotic twin pregnancies are at increased risk of perinatal complications, primarily owing to the risk of cord entanglement. There is no recommendation on whether such pregnancies should be managed in hospital or can be safely managed in an outpatient setting, and the timing of planned delivery is also a subject of debate. The aim of this study was to compare the perinatal outcomes of inpatient vs outpatient fetal surveillance approaches employed among 22 participating study centers, and to calculate the fetal and neonatal death rates according to gestational age, in non-anomalous monoamniotic twins from 26 weeks' gestation. METHODS: The MONOMONO study was a multinational cohort study of consecutive women with monochorionic monoamniotic twin pregnancies, who were referred to 22 university hospitals in Italy, the USA, the UK and Spain, from January 2010 to January 2017. Only non-anomalous uncomplicated monoamniotic twin pregnancies with two live fetuses at 26 + 0 weeks' gestation were included in the study. In 10 of the centers, monoamniotic twins were managed routinely as inpatients, whereas in the other 12 centers they were managed routinely as outpatients. The primary outcome was intrauterine fetal death. We also planned to assess fetal and neonatal death rates according to gestational age per 1-week interval. Outcomes are presented as odds ratio (OR) with 95% CIs. The main outcome was analyzed using both standard logistic regression analysis, in which each fetus was treated as an independent unit, and a generalized mixed-model approach, with each twin pair treated as a cluster unit, considering that the outcome for a twin is not independent of that of its cotwin. RESULTS: 195 consecutive pregnant women with a non-anomalous uncomplicated monoamniotic twin gestation (390 fetuses) were included. Of these, 75 (38.5%) were managed as inpatients and 120 (61.5%) as outpatients. The overall perinatal loss rate was 10.8% (42/390) with a peak fetal death rate of 4.3% (15/348) occurring at 29 weeks' gestation. There was no significant difference in mean gestational age at delivery (31 weeks), birth weight (∼1.6 kg), or emergency delivery rate between the inpatient and outpatient surveillance groups. Based on generalized mixed-model analysis, there was no statistically significant difference in fetal death rates between inpatient management commencing from around 26 weeks compared with outpatient surveillance protocols from 30 weeks (3.3% vs 10.8%; adjusted OR 0.21 (95% CI, 0.04-1.17)). Maternal length of stay in the hospital was 42.1 days in the inpatient group, and 7.4 days in the outpatient group (mean difference 34.70 days (95% CI, 31.36-38.04 days). From 32 + 0 to 36 + 6 weeks, no fetal or neonatal death in either group was recorded. 46 fetuses were delivered after 34 + 0 weeks, and none of them died in utero or within the first 28 days postpartum. CONCLUSION: In uncomplicated monoamniotic twins, inpatient surveillance is associated with similar fetal mortality as outpatient management. After 31 + 6 weeks, and up to 36 + 6 weeks, there were no intrauterine fetal deaths or neonatal deaths. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.

A 1-year pilot cross-sectional study was performed to assess eating behaviours and lifestyle among Chinese and Arab pregnant immigrants to Italy. A number of 95 Chinese and 83 Arab women were interviewed. Two ethnic-specific food frequency questionnaires were designed to reflect the habitual diet of women belonging to these ethnic groups. Food items frequency of consumption was discussed using healthy eating guidelines. In both populations, women met healthy eating guidelines, except for salt intake, which was double than recommended; meat, sweet products and sugar-sweetened beverages were consumed more frequently than recommended, while olive oil and yogurt were eaten less frequently. Chinese women did not reach the recommendations for dairy products and fatty fish and exceeded those for red and processed meat, whereas Arab women exceeded the recommendations for cheese. Our findings suggest that the Italian food environment did not significantly affect Chinese and Arab pregnant immigrants' diet.

Shortly after the acceptance of our review [1] an additional study on the use of valacyclovir in pregnant women with primary cytomegalovirus (CMV) infection to prevent vertical transmission has been published by De Santis et al [2]. The authors reported a case series of 12 pregnant women treated with off-label valacyclovir 8g per day following primary CMV infection in the first half of pregnancy and stopped in case of negative amniocentesis. The observed rate of positivity at amniocentesis was 17% (2 positive amniocentesis of 12 performed) compatible with a ≈50% reduction of vertical transmission when compared to the 30-35% rate reported in literature [3]. These results are consistent to those reported by Shahar-Nissan K et al in the preliminary report on their clinical placebo-controlled trial [4] and confirm that valacyclovir may reduce the rate of vertical transmission by the time of amniocentesis. However, among the 10 pregnant women with a negative amniocentesis described by De Santis, three delivered a congenitally infected newborn of which one developed moderate unilateral sensory neural loss at 18 months of age. Amongst these three women with negative amniocentesis who delivered a congenitally infected newborn, two presented a new CMV DNAemia after valacyclovir discontinuation. The authors interpret their finding as the result of an efficient control of viral replication and prevention of during the antiviral treatment, with subsequent resurgence of viral and vertical transmission. They suggested the need of controlled trial to evaluate valacyclovir treatment prolonged until the delivery regardless of amniocentesis results. However the possibility of false negative amniocentesis cannot be completely excluded. In particular the authors used 0.4mL of amniotic fluids to extract the CMV-DNA which is lower compared to those used in other reference laboratory (1mL) [5] and this could have affected the sensitivity of the test. In another recent paper (not captured by our review of literature since indexed with the keyword “citomegalovirus” unlike “cytomegalovirus”), De Santis et al described a case series on the use of high dose valacyclovir (8g/day) until delivery in confirmed fetal asymptomatic CMV infections [6]. Of the eleven in utero treated newborns, only one was symptomatic at birth and he developed profound bilateral hearing loss at six month requiring bilateral cochlear implant. Another developed a sensorineural hearing loss at 8 months of age. Surprisingly, three newborns had negative serology and virological tests at birth inducing authors to speculate that treatment can even allow viral clearance in case of low amniotic fluids viral load. To sum up, these two studies confirmed data from previous literature, namely the excellent maternal tolerance and the benefit of valacyclovir in reducing fetal CMV infections at time of amniocentesis [4] and the possible role of the drug in the in utero treatment of confirmed fetal infection [7]. We look forward to see the results of the still partially published randomized, double-blind, placebo-controlled study [4], which will probably add further important information.

Background/aim The aim of the study was to investigate boost volume definition, doses, and delivery techniques for rectal cancer dose intensification. Patients and methods An online survey was made on 25 items (characteristics, simulation, imaging, volumes, doses, planning and treatment). Results Thirty-eight radiation oncologists joined the study. Twenty-one delivered long-course radiotherapy with dose intensification. Boost volume was delineated on diagnostic magnetic resonance imaging (MRI) in 18 centres (85.7%), and computed tomography (CT) and/or positron emission tomography-CT in 9 (42.8%); 16 centres (76.2%) performed co-registration with CT-simulation. Boost dose was delivered on gross tumor volume in 10 centres (47.6%) and on clinical target volume in 11 (52.4%). The most common total dose was 54-55 Gy (71.4%), with moderate hypofractionation (85.7%). Intensity-modulated radiotherapy (IMRT) was used in all centres, with simultaneous integrated boost in 17 (80.8%) and image-guidance in 18 (85.7%). Conclusion A high quality of treatment using dose escalation can be inferred by widespread multidisciplinary discussion, MRI-based treatment volume delineation, and radiation delivery relying on IMRT with accurate image-guided radiation therapy protocols.

Objective: Expectant management in patients with prelabor preterm rupture of membranes between between 340/7 and 36 6/7 weeks (late preterm pPROM or LpPROM) has been shown to decrease the burden of prematurity, when compared to immediate delivery. As the severity of prematurity depends on gestational age (GA) at PROM, and PROM to delivery interval, we first investigated how such variables affect neonatal outcomes (NO). Second, we assessed the risk of neonatal sepsis. Study design: retrospective cohort study on neonatal morbidity among singleton infants born to expectantly managed mothers with LpPROM in five hospitals affiliated with three Italian academic institutions. The primary NO was a composite of neonatal death, non-invasive (cPAP) or invasive (mechanical ventilation) respiratory support, hypoglycemia (< 44 mg/dl needing therapy), newborn sepsis, confirmed seizures, stroke, intraventricular hemorrhage (IVH), basal nuclei anomalies, cardiopulmonary resuscitation, umbilical-cord-blood arterial pH < 7.0 or base excess < -12.5, and prolonged hospitalization (≥ 5 days). Univariate analysis described differences in the population according to GA at delivery. Multivariate logistic regression was then used to investigate the effects of GA at PROM, and PROM to delivery interval on the NO. Results: 258/606 (42.6 %) women with LpPROM were expectantly managed, as they did not deliver within the first 24 h. The median latency duration was 2 (95 %CI 1−3) days, having no effect on neonatal morbidity on multivariate analysis. Multivariate analysis also showed increased risks of adverse NO among PROM at 34 (OR 2.3 95 %CI 1.03−5.1) but not at 35 weeks when compared to 36 weeks, and among women receiving antenatal corticosteroids (OR 3.6 95 %CI 1.3−9.7), while antibiotic treatment showed a non-significant protective effect (OR 0.2 95 %CI 0.04−1.02). Prevalence of neonatal sepsis was 0.8 % (2/258) Conclusion: Expectant management of LpPROM should be encouraged especially between 34+0 and 34+6 weeks’, when the burden of prematurity is the greatest. Antibiotics may have beneficial effects, while careful consideration should be given to antenatal corticosteroids until future studies specifically address LpPROM.

Objectives:The primary objective was to quantify the risk of perinatal mortality in non‐anomalous monochorionic monoamniotic (MCMA) twin pregnancies complicated by birth‐weight (BW) discordance. The secondary objectives were to investigate the effect of inpatientvsoutpatient fetal monitoring on the risk of mortality in weight‐discordant MCMA twin pregnancies, and to explore the predictive accuracy of BW discordance for perinatal mortality. Methods:This analysis included data on 242 MCMA twin pregnancies (484 fetuses) from three major research collaboratives on twin pregnancy (MONOMONO, STORK and NorSTAMP). The primary outcomes were the risks of intrauterine (IUD), neonatal (NND) and perinatal (PND) death, according to weight discordance at birth from ≥ 10% to ≥ 30%. The secondary outcomes were the association of inpatientvsoutpatient fetal monitoring with the risk of mortality in weight‐discordant pregnancies, and the accuracy of BW discordance in predicting mortality. Logistic regression and receiver‐operating‐characteristics‐curve analyses were used to analyze the data. Results:The risk of IUD was significantly increased in MCMA twin pregnancies with BW discordance ≥ 10% (odds ratio (OR), 2.2; 95% CI, 1.1–4.4;P= 0.022) and increased up to an OR of 4.4 (95% CI, 1.3–14.4;P= 0.001) in those with BW discordance ≥ 30%. This association remained significant on multivariate logistic regression analysis for BW‐discordance cut‐offs ≥ 20%. However, weight discordance had low predictive accuracy for mortality, with areas under the receiver‐operating‐characteristics curve of 0.60 (95% CI, 0.46–0.73), 0.52 (95% CI, 0.33–0.72) and 0.57 (95% CI, 0.45–0.68) for IUD, NND and PND, respectively. There was no difference in the risk of overall IUD, single IUD, double IUD, NND or PND between pregnancies managed as an inpatient compared with those managed as an outpatient, for any BW‐discordance cut‐off. Conclusions:MCMA twin pregnancies with BW discordance are at increased risk of fetal death, signaling a need for increased levels of monitoring. Despite this, the predictive accuracy for mortality is low; thus, detection of BW discordance alone should not trigger intervention, such as iatrogenic delivery. The current data do not demonstrate an advantage of inpatient over outpatient management in these cases. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Objective: To describe morbidity in neonates born by cesarean section (CS) before labor between 34+0 and 38+6 weeks, stratified by gestational age.Methods: Cohort study from five Italian tertiary care hospitals. Consecutive singleton pregnancies delivered by CS before labor between 34+0 and 38+6 weeks of gestation from January 2010 to August 2011 were included. Women in labor, with premature rupture of membranes, or with previous administration of steroids were excluded. The incidence of neonatal complication by gestational week was calculated.Results: A total of 1135 cases were analyzed. Composite adverse neonatal outcomes, respiratory distress syndrome, transient tachypnea and use of continuous airway positive pressure decreased from 50%, 28%, 5% and 22% at 34 weeks of gestation, to 4.7%, 1.0%, 0.9% and 0.3% at 38 weeks of gestation. Multivariate analysis showed that the only variable independently associated with composite adverse neonatal outcome was gestational age at delivery (adjusted odds ratio 0.49; 95% confidence interval 0.39-0.61).Conclusions: The prevalence of neonatal complications in newborns delivered by CS before labor halves at each week of gestation from 34 to 38 weeks. Nonetheless complications, and mainly respiratory problems, are still present at early term gestation.

BACKGROUND:To understand the role of fetal spine position in determining a fetal head position at the time of birth and modality of delivery. PATIENTS AND METHODS: This was a multicenter prospective observational study. Fetal occiput and spine position were evaluated by intrapartum ultrasound. Eighty-six women were eligible for inclusion in the study. Occiput rotational movements and modality of delivery in relation to the fetal spine position were investigated. RESULTS: At the beginning of labor, fetal occiput was in a posterior position in 52.3% of cases and, in 81.5% of cases the spine was in an anterior transverse position. At birth, occiput and spine were both in an anterior position in 90.4% of cases. The rate of cesarean sections in the SP group was significantly higher than the rate in the SAT group (50% vs. 8%, p < 0.0007). Instead, the rate of vaginal deliveries without intervention in the SP group was significantly lower than the rate in the SA group (14% vs. 71%, p < 0.0001). CONCLUSIONS: Fetal spine position could have an important role in determining fetal occiput position at birth. Spine position might play a crucial role in the outcome of delivery.

Background Several randomized controlled trials (RCTs) compared induction of labour with expectant management in non-diabetic women with suspected fetal macrosomia. Objective To evaluate the effects of labour induction for suspected fetal macrosomia. Search strategy Literature search in electronic databases. Selection criteria We included all RCTs of suspected fetal macrosomia comparing labour induction with expectant management in term pregnancy. Data collection and analysis The primary outcome was the incidence of caesarean delivery. Main results Four RCTs, including 1190 non-diabetic women with suspected fetal macrosomia at term, were analysed. Pooled data did not show a significant difference in incidence of caesarean delivery [relative risk (RR) 0.91, 95% confidence interval (CI) 0.76–1.09], operative and spontaneous vaginal delivery, shoulder dystocia, intracranial haemorrhage, brachial plexus palsy, Apgar score

Endocannabinoids are natural lipids able to bind to cannabinoid and vanilloid receptors. Their biological actions at the central and peripheral level are under the tight control of the proteins responsible for their synthesis, transport and degradation. In the last few years, several reports have pointed out these lipid mediators as critical signals, together with sex hormones and cytokines, in various aspects of animal and human reproduction. The identification of anandamide (AEA) and 2-arachidonoylglycerol (2-AG) in reproductive cells and tissues of invertebrates, vertebrates and mammals highlights the key role played by these endogenous compounds along the evolutionary axis. Here, we review the main actions of endocannabinoids on female and male reproductive events, and discuss the interplay between them, steroid hormones and cytokines in regulating fertility. In addition, we discuss the involvement of endocannabinoid signalling in ensuring a correct chromatin remodeling, and hence a good DNA quality, in sperm cells.

Noninvasive in vivo imaging of gene expression is desirable to monitor gene transfer in both animal models and humans. Reporter transgenes with low endogenous expression levels are instrumental to this end. The human somatostatin receptor 2 (hSSTR2) has low expression levels in a variety of tissues, including muscle and liver. We tested the possibility of noninvasively and quantitatively monitoring hSSTR2 transgene expression, following adeno-associated viral (AAV) vector-mediated gene delivery to murine muscle and liver by positron emission tomography (PET) using 68gallium-DOTA- Tyr3-Thr8-octreotate (68Ga-DOTATATE) as a highly specific SSTR2 ligand. Repetitive PET imaging showed hSSTR2 signal up to 6 months, which corresponds to the last time point of the analysis, after gene delivery in both transduced tissues. The levels of tracer accumulation measured in muscle and liver after gene delivery were significantly higher than in control tissues and correlated with the doses of AAV vector administered. As repetitive, quantitative, noninvasive imaging of AAV-mediated SSTR2 gene transfer to muscle and liver is feasible and efficient using PET, we propose this system to monitor the expression of therapeutic genes coexpressed with SSTR2. © 2011, Mary Ann Liebert, Inc.