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Objectives: To explore whether early first-trimester ultrasound can predict the third-trimester sonographic stage of placenta accreta spectrum (PAS) disorder and to elucidate whether combining first-trimester ultrasound findings with the sonographic stage of PAS disorder can stratify the risk of adverse surgical outcome in women at risk for PAS disorder. Methods: This was a retrospective analysis of prospectively collected data from women with placenta previa, and at least one previous Cesarean delivery (CD) or uterine surgery, for whom early first-trimester (5-7 weeks' gestation) ultrasound images could be retrieved. The relationship between the position of the gestational sac and the prior CD scar was assessed using three sonographic markers for first-trimester assessment of Cesarean scar (CS) pregnancy, reported by Cali et al. (crossover sign (COS)), Kaelin Agten et al. (implantation of the gestational sac on the scar vs in the niche of the CS) and Timor-Tritsch et al. (position of the center of the gestational sac below vs above the midline of the uterus), by two different examiners blinded to the final diagnosis and clinical outcome. The primary aim of the study was to explore the association between first-trimester ultrasound findings and the stage of PAS disorder on third-trimester ultrasound. Our secondary aim was to elucidate whether the combination of first-trimester ultrasound findings and sonographic stage of PAS disorder can predict surgical outcome. Logistic regression analysis and area under the receiver-operating-characteristics curve (AUC) were used to analyze the data. Results: One hundred and eighty-seven women with vasa previa were included. In this cohort, 79.6% (95% CI, 67.1-88.2%) of women classified as COS-1, 94.4% (95% CI, 84.9-98.1%) of those with gestational-sac implantation in the niche of the prior CS and 100% (95% CI, 93.4-100%) of those with gestational sac located below the uterine midline, on first-trimester ultrasound, were affected by the severest form of PAS disorder (PAS3) on third-trimester ultrasound. On multivariate logistic regression analysis, COS-1 (odds ratio (OR), 7.9 (95% CI, 4.0-15.5); P < 0.001), implantation of the gestational sac in the niche (OR, 29.1 (95% CI, 8.1-104); P < 0.001) and location of the gestational sac below the midline of the uterus (OR, 38.1 (95% CI, 12.0-121); P < 0.001) were associated independently with PAS3, whereas parity (P = 0.4) and the number of prior CDs (P = 0.5) were not. When translating these figures into diagnostic models, first-trimester diagnosis of COS-1 (AUC, 0.94 (95% CI, 0.91-0.97)), pregnancy implantation in the niche (AUC, 0.92 (95% CI, 0.89-0.96)) and gestational sac below the uterine midline (AUC, 0.92 (95% CI, 0.88-0.96)) had a high predictive accuracy for PAS3. There was an adverse surgical outcome in 22/187 pregnancies and it was more common in women with, compared to those without, COS-1 (P < 0.001), gestational-sac implantation in the niche (P < 0.001) and gestational-sac position below the uterine midline (P < 0.001). On multivariate logistic regression analysis, third-trimester ultrasound diagnosis of PAS3 (OR, 4.3 (95% CI, 2.1-17.3)) and first-trimester diagnosis of COS-1 (OR, 7.9 (95% CI, 4.0-15.5); P < 0.001), pregnancy implantation in the niche (OR, 29.1 (95% CI, 8.1-79.0); P < 0.001) and position of the sac below the uterine midline (OR, 6.6 (95% CI, 3.9-16.2); P < 0.001) were associated independently with adverse surgical outcome. When combining the sonographic coordinates of the three first-trimester imaging markers, we identified an area we call high-risk-for-PAS triangle, which may enable an easy visual perception and application of the three methods to prognosticate the risk for CS pregnancy and PAS disorder, although it requires validation in large prospective studies. Conclusions: Early first-trimester sonographic assessment of pregnancies with previous CD can predict reliably ultrasound stage of PAS disorder. Combination of findings on first-trimester ultrasound with second- and third-trimester ultrasound examination can stratify the surgical risk in women affected by a PAS disorder. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

To evaluate perioperative outcomes and the prognostic role of the tramline sign in a cohort of women with anterior placenta previa. Retrospective analysis of 3D ultrasound volumes from women with anterior placenta previa who underwent ultrasound examination beyond 32 weeks. 3D and 3D color volumes were obtained from a sagittal section of the uterus bisecting a partially full bladder and processed using Crystal Vue and Crystal Vue Flow rendering to look for the "tramline sign". "Partial obliteration" was defined as a loss of some or part of the uterine-serosal interface and "full obliteration" as when both interfaces were interrupted. Postnatal ascertainment of placenta accreta spectrum (PAS) was confirmed by findings recorded intraoperatively or on a pathology report. 65 cases were included. The tramline sign was "partially" (17) or "fully" (19) obliterated in 36 cases (55.4 %), and present in 29 (44.6 %). Obliteration was associated with earlier gestational age at delivery (35 + 1 (26 + 3-38 + 3) vs. 36 + 4 (25 + 3-38 + 0) weeks, p = 0.005), greater estimated blood loss (800 (400-11 000) vs. 600 (300-2100) mls, p = 0.003), longer operative time (155 (60-240) vs. 54 (25-80) minutes, p 0.001), higher rate of hysterectomy (97.2 % vs. 0.0 %, p 0.001), longer postoperative admission (7 (3-19) vs. 3 (1-5) days, p 0.001) and a 100 % rate of postnatal diagnosis of PAS. The finding of an "obliterated" tramline sign identified all women that required hysterectomy and all cases of PAS. A "partially or fully obliterated" tramline sign is strongly associated with indicators of operative complexity, the postnatal confirmation of PAS, and the need for peripartum hysterectomy.ZIEL: Beurteilung der perioperativen Outcomes und der prognostischen Rolle des sogenannten Tramline-Zeichens in einer Kohorte von Frauen mit anteriorer Placenta praevia. Retrospektive Analyse der 3D-Ultraschallvolumina von Frauen mit anteriorer Placenta praevia, bei denen nach der 32. Woche eine Ultraschalluntersuchung durchgeführt wurde. 3D- und 3D-Farbvolumina wurden aus einem sagittalen Abschnitt des Uterus gewonnen, der die teilweise gefüllte Blase halbierte und mit Crystal Vue und Crystal Vue Flow 65 Fälle wurden eingeschlossen. Das Tramline-Zeichen war in 36 Fällen (55,4 %) „teilweise“ (17) oder „vollständig“ (19) ausgelöscht und in 29 (44,6 %) vorhanden. Die Auslöschung war assoziiert mit einer früheren Schwangerschaftswoche bei Entbindung (35 + 1 (26 + 3–38 + 3) vs. 36 + 4 (25 + 3–38 + 0); p = 0,005), einem höheren geschätzten Blutverlust (800 (400–11 000) vs. 600 (300–2100) ml; p = 0,003), einer längeren Operationszeit (155 (60–240) vs. 54 (25–80) Minuten; p 0,001), einer höheren Hysterektomierate (97,2 % vs. 0,0 %; p 0,001), einem längeren postoperativen Aufenthalt (7 (3–19) vs. 3 (1–5) Tage; p 0,001) und einer 100 %igen Rate der postnatalen Diagnose der PAS. Der Befund eines „ausgelöschten“ Tramline-Zeichens identifizierte alle Frauen, bei denen eine Hysterektomie erforderlich war, sowie alle Fälle von PAS. Ein „teilweise oder vollständig ausgelöschtes“ Tramline-Zeichen ist stark mit Indikatoren für die operative Komplexität, mit der postnatalen Diagnose einer PAS und der Notwendigkeit einer peripartalen Hysterektomie assoziiert.

Objective: The aim of this study was to report the rate of additional anomalies detected exclusively at prenatal magnetic resonance imaging (MRI) in fetuses with isolated severe ventriculomegaly undergoing neurosonography. Method: Multicenter, retrospective, cohort study involving 20 referral fetal medicine centers in Italy, United Kingdom, Spain and Denmark. Inclusion criteria were fetuses affected by isolated severe ventriculomegaly (≥15 mm), defined as ventriculomegaly with normal karyotype and no other additional central nervous system (CNS) and extra-CNS anomalies on ultrasound. In all cases, a multiplanar assessment of fetal brain as suggested by ISUOG guidelines on fetal neurosonography had been performed. The primary outcome was the rate of additional CNS anomalies detected exclusively at fetal MRI within two weeks from neurosonography. Subgroup analyses according to gestational age at MRI (

The antenatal diagnosis of placenta accreta spectrum (PAS) is in large part subjective and based on expert interpretation. The aim of this study was to externally evaluate a recently developed staging system based on specific and defined prenatal ultrasound (US) features in a cohort of women at risk of PAS undergoing specialist prenatal US, in particular relating to surgical morbidity at delivery.Database study of cases with confirmed placenta previa. In all, the placenta was evaluated in a systematic fashion. PAS was subclassified in PAS0-PAS3 according to the loss of clear zone, placental lacunae, bladder wall interruption, uterovesical hypervascularity and increased vascularity in the parametrial region.43 cases were included, of whom 33 had major placenta previa. 31 cases were categorized as PAS0; 3, 4 and 5 cases as PAS1, PAS2 and PAS3, respectively. All women underwent caesarean section and hysterectomy was required in 10. The comparison of the perinatal outcomes among the PAS categories yielded greater operative time (50 (35-129) minutes for PAS0 vs 70 (48-120) for PAS1 vs 95 (60-150) for PAS2 vs 100 (87-180) for PAS3, p 0.001) and estimated blood loss (800 (500-2500) mls for PAS0 vs 3500 (800-7500) for PAS1 vs 2850 (500-7500) for PAS2 vs 6000 (2500-11000) for PAS3, p 0.001) for the highest PAS categories, which were also associated with a higher rate of hysterectomy (p 0.001), blood transfusion (p = 0.002) and admission to ITU or HDU (p 0.001) and longer postoperative admission of 3 (1-9) days for PAS0 vs 3 (2-12) for PAS1 vs 4.5 (3-6) for PAS2 vs 5 (3-22) for PAS3, p = 0.02.Perioperative complications are closely associated with PAS stage. This information is useful for counselling women and may be important in allocating staff and infrastructure resources at the time of delivery.

To evaluate the diagnostic accuracy of a new ultrasound sign, intracervical lakes (ICL), in predicting the presence of placenta accreta spectrum (PAS) disorder and delivery outcome in patients with placenta previa or low-lying placenta.This was a retrospective multicenter study of women with placenta previa or low-lying placenta at ≥ 26 weeks' gestation, who were referred to three Italian tertiary units from January 2015 to September 2018. The presence of ICL, defined as tortuous anechoic spaces within the cervix which appeared to be hypervascular on color Doppler, was evaluated on ultrasound images obtained at the time of referral. The primary aim was to explore the diagnostic accuracy of ICL in detecting the presence and depth of PAS disorder. The secondary aim was to explore the accuracy of this sign in predicting total estimated blood loss, antepartum bleeding, major postpartum hemorrhage at the time of Cesarean section and need for Cesarean hysterectomy. The diagnostic accuracy of ICL in combination with typical sonographic signs of PAS disorder, was assessed by computing summary estimates of sensitivity, specificity, positive and negative predictive values, positive and negative likelihood ratios and diagnostic odds ratios (DOR).A total of 332 women with placenta previa or low-lying placenta were included in the analysis, with a median maternal age of 33.0 (interquartile range, 29.0-37.0) years. ICL were noted in 15.1% of patients. On logistic regression analysis, the presence of ICL was associated independently with major postpartum hemorrhage (odds ratio (OR), 3.3 (95% CI, 1.6-6.5); P 0.001), Cesarean hysterectomy (OR, 7.0 (95% CI, 2.1-23.9); P 0.001) and placenta percreta (OR, 2.8 (95% CI, 1.3-5.8); P ≤ 0.01), but not with the presence of any PAS disorder (OR, 1.6 (95% CI, 0.7-3.5); P = 0.2). Compared with the group of patients without ultrasound signs of PAS disorder, the presence of at least one typical sonographic sign of PAS disorder in combination with ICL had a DOR of 217.2 (95% CI, 27.7-1703.4; P 0.001) for placenta percreta and of 687.4 (95% CI, 121.4-3893.0; P 0.001) for Cesarean hysterectomy.ICL may represent a marker of deep villus invasion in women with suspected PAS disorder on antenatal sonography and anticipate the occurrence of severe maternal morbidity. Copyright © 2019 ISUOG. Published by John WileySons Ltd.Los espacios intracervicales como marcador ecográfico de trastornos del espectro de la placenta acreta en pacientes con placenta previa o placenta baja OBJETIVO: Evaluar la precisión del diagnóstico de un nuevo indicio de ultrasonido, los espacios intracervicales (EIC), para predecir la presencia de trastornos del espectro de la placenta acreta (EPA) y el resultado del parto en pacientes con placenta previa o placenta baja. MÉTODOS: Este fue un estudio multicéntrico retrospectivo de mujeres con placenta previa o placenta baja a ≥ 26 semanas de gestación, que se remitieron a tres unidades terciarias italianas desde enero de 2015 a septiembre de 2018. Se evaluó la presencia de EIC, definida como espacios anecoicos tortuosos dentro del cuello uterino que parecían ser hipervasculares en el Doppler a color, en imágenes de ecografías obtenidas en el momento de la remisión. El objetivo principal fue estudiar la precisión del diagnóstico mediante EIC en la detección de la presencia y la profundidad de un trastorno del EPA. El objetivo secundario fue explorar la precisión de este indicador para predecir la pérdida total estimada de sangre, la hemorragia antes del parto, la hemorragia puerperal importante en el momento de la cesárea y la necesidad de una histerectomía por cesárea. La precisión diagnóstica de EIC, en combinación con los indicios ecográficos típicos de los trastornos del EPA, se evaluó calculando estimaciones estadísticas descriptivas de la sensibilidad, la especificidad, los valores predictivos positivos y negativos, los cocientes de verosimilitud positivos y negativos y las razones de momios del diagnóstico (RMD). RESULTADOS: En el análisis se incluyó un total de 332 mujeres con placenta previa o placenta baja, con una mediana de la edad materna de 33,0 años (rango intercuartil, 29,0-37,0). Se observaron EIC en el 15,1% de las pacientes. En el análisis de regresión logística, la presencia de EIC se asoció de forma independiente con la hemorragia puerperal grave (razón de momios (RM), 3,3 (IC 95%, 1,6-6,5); P0,001), la histerectomía por cesárea (RM, 7,0 (IC 95%, 2,1-23,9); P0,001) y la placenta percreta (RM, 2,8 (IC 95%, 1,3-5,8); P≤0,01), pero no con la presencia de ningún trastorno del EPA (RM, 1,6 (IC 95%, 0,7-3,5); P=0,2). En comparación con el grupo de pacientes sin indicios de ultrasonido de algún trastorno del EPA, la presencia de al menos un indicio ecográfico típico de trastorno del EPA en combinación con EIC tuvo una RMD de 217,2 (IC 95%, 27,7-1703,4; P0,001) para la placenta percreta y de 687,4 (IC 95%, 121,4-3893,0; P0,001) para la histerectomía por cesárea. CONCLUSIÓN: Los EIC pueden representar un marcador de invasión profunda de las vellosidades en mujeres con sospecha de algún trastorno del EPA basado en la ecografía prenatal y anticipar la presencia de una morbilidad materna grave.作为胎盘增生频谱紊乱超声征象的前置胎盘或低位胎盘患者宫颈内血池 目标: 评估一种新型超声征象宫颈内血池(ICL)在预测前置胎盘或低位胎盘患者胎盘增生频谱(PAS)紊乱和分娩结果中的诊断准确性。 方法: 这是一项针对2015年1月至2018年9月间，转诊至意大利三家三级医院的妊娠满26周前置胎盘或低位胎盘女性患者的回顾性多中心研究。评估转诊时获得的超声图像确定是否存在ICL，即彩色多普勒超声检测显示宫颈内出现血管增生的迂曲无回声间隙。首要目的是研究ICL在检测PAS紊乱及其深度时的诊断准确性。次要目的是研究该征象在估计剖宫产预计总失血量、产前出血、产后大出血，以及是否需要进行剖宫产子宫切除术时的准确性。计算敏感性、特异性、阳性和阴性预测值、阳性和阴性似然比和诊断比值比(DOR)汇总估算，以此评估ICL结合典型PAS紊乱超声征象的诊断准确性。 结果: 总共分析了332名前置胎盘或低位胎盘女性患者，孕产妇年龄中位数为33.0岁(四分位间距29.0 - 37.0)。发现15.1%的病患出现ICL。逻辑回归分析表明ICL与产后大出血(比值比OR 3.3 (95% CI, 1.6-6.5); P0.001))、剖宫产子宫切除术(OR, 7.0 (95% CI, 2.1-23.9); P0.001)以及植入胎盘(OR, 2.8 (95% CI, 1.3-5.8); P≤0.01)独立相关，但与任何PAS紊乱无关(OR, 1.6 (95% CI, 0.7-3.5); P=0.2)。对照未出现PAS紊乱超声征象的病患组，(植入胎盘中)至少一种典型的PAS紊乱超声征象结合ICL的DOR为217.2 (95% CI, 27.7-1703.4; P0.001)，剖宫产子宫切除术为687.4 (95% CI, 121.4-3893.0; P0.001)。 结论: ICL可能是一种产前超声检测中显示疑似PAS紊乱的孕产妇深绒毛浸润标志物，可以预测重度孕产妇疾病发病率。.

Objective To evaluate the level of agreement in the prenatal magnetic resonance imaging (MRI) assessment of the presence and severity of placenta accreta spectrum (PAS) disorders between examiners with expertise in the diagnosis and management of these conditions. Methods This was a secondary analysis of a prospective study including women with placenta previa or low-lying placenta and at least one prior Cesarean delivery or uterine surgery, who underwent MRI assessment at a regional referral center for PAS disorders in Italy, between 2007 and 2017. The MRI scans were retrieved from the hospital electronic database and assessed by four examiners, who are considered to be experts in the diagnosis and surgical management of PAS disorders. The examiners were blinded to the ultrasound diagnosis, histopathological findings and clinical data of the patients. Each examiner was asked to assess 20 features on the MRI scans, including the presence, depth and topography of placental invasion. Depth of invasion was defined as the degree of adhesion and invasion of the placenta into the myometrium and uterine serosa (placenta accreta, increta or percreta) and the histopathological examination of the removed uterus was considered the reference standard. Topography of the placental invasion was defined as the site of placental invasion within the uterus in relation to the posterior bladder wall (posterior upper bladder wall and uterine body, posterior lower bladder wall and lower uterine segment and cervix or no visible bladder invasion) and the site of invasion at surgery was considered the reference standard. The degree of interrater agreement (IRA) was evaluated by calculating both the percentage of observed agreement among raters and the Fleiss kappa (κ) value. Results Forty-six women were included in the study. The median gestational age at MRI was 33.8 (interquartile range, 33.1-34.0) weeks. A final diagnosis of placenta accreta, increta and percreta was made in 15.2%, 17.4% and 50.0% patients, respectively. There was excellent agreement between the four examiners in the assessment of the overall presence of a PAS disorder (IRA, 92.1% (95% CI, 86.8-94.0%); κ, 0.90 (95% CI, 0.89-1.00)). However, there was significant heterogeneity in IRA when assessing the different MRI signs suggestive of a PAS disorder. There was excellent agreement between the examiners in the identification of the depth of placental invasion on MRI (IRA, 98.9% (95% CI, 96.8-100.0%); κ, 0.95 (95% CI, 0.89-1.00)). However, agreement in assessing the topography of placental invasion was only moderate (IRA, 72.8% (95% CI, 72.7-72.9%); κ, 0.56 (95% CI, 0.54-0.66)). More importantly, when assessing parametrial invasion, which is one of the most significant prognostic factors in women affected by PAS, the agreement was substantial and moderate in judging the presence of invasion in the coronal (IRA, 86.6% (95% CI, 86.5-86.7%); κ, 0.69 (95% CI, 0.59-0.71)) and axial (IRA, 78.6% (95% CI, 78.5-78.7%); κ, 0.56 (95% CI, 0.33-0.60)) planes, respectively. Likewise, interobserver agreement in judging the presence and the number of newly formed vessels in the parametrial tissue was moderate (IRA, 88.0% (95% CI, 88.0-88.1%); κ, 0.59 (95% CI, 0.45-0.68)) and fair (IRA, 66.7% (95% CI, 66.6-66.7%); κ, 0.22 (95% CI, 0.12-0.37)), respectively. Conclusions MRI has excellent interobserver agreement in detecting the presence and depth of placental invasion, while agreement between the examiners is lower when assessing the topography of invasion. The findings of this study highlight the need for a standardized MRI staging system for PAS disorders, in order to facilitate objective correlation between prenatal imaging, pregnancy outcome and surgical management of these patients. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Objective To ascertain the diagnostic accuracy of ultrasound in detecting abnormally invasive placenta (AIP) during the first trimester of pregnancy (11-14 weeks' gestation) in women at risk for this condition. Methods This was a retrospective analysis of data collected prospectively from women at risk for AIP based upon the presence of at least one prior Cesarean section (CS) and/or uterine surgery and placenta previa, who had ultrasound assessment for AIP at the time of the 11-14-week scan. The ultrasound signs explored in the present study were: loss of the clear zone, placental lacunae, bladder wall interruption and uterovesical hypervascularity. The potential of ultrasound and different ultrasound signs to predict the different types of AIP was assessed by computing summary estimates of sensitivity, specificity, diagnostic odds ratio (DOR) and positive (LR+) and negative (LR-) likelihood ratios. Results One hundred and eighty-eight women with placenta previa and at least one previous CS or uterine surgery were included in the study. All the explored ultrasound signs were associated significantly with the occurrence of AIP. Overall, when at least one ultrasound sign was used to make the diagnosis, ultrasound had a sensitivity of 84.3% (95% CI, 74.7-91.4%), specificity of 61.9% (95% CI, 51.9-71.2%), DOR of 8.6 (95% CI, 4.1-19.3), LR+ of 2.2 (95% CI, 1.7-2.9) and LR- of 0.3 (95% CI, 0.1-0.4) in detecting AIP. Using two ultrasound signs to label a case as positive increased the diagnostic accuracy in terms of specificity, although it did not affect sensitivity. Among the different ultrasound signs, loss of the clear zone had a sensitivity of 84.3% (95% CI, 74.7-91.4%) and a specificity of 81.9% (95% CI, 73.2-88.7%) in detecting AIP, while sensitivities for placental lacunae and bladder wall interruption were 78.3% (95% CI, 67.9-86.6%) and 75.9% (95% CI, 65.3-84.6%), respectively, and specificities were 81.0% (95% CI, 72.1-88.0%) and 99.1% (95% CI, 94.8-100.0%), respectively. The optimal combination of sensitivity and specificity was achieved when at least two imaging signs of AIP were used in the diagnostic algorithm. Conclusions AIP can be detected from the first trimester of pregnancy in women at risk for this condition, and ultrasound performed between 11 and 14 weeks' gestation has an overall good diagnostic accuracy for detecting all types of AIP. However, these findings are applicable only to women with placenta previa and prior uterine scar. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.

The primary aim of this systematic review was to ascertain whether ultrasound signs suggestive of abnormally invasive placenta (AIP) are present in the first trimester of pregnancy. Secondary aims were to ascertain the strength of association and the predictive accuracy of such signs in detecting AIP in the first trimester.An electronic search of MEDLINE, EMBASE, CINAHL and Cochrane databases (2000-2016) was performed. Only studies reporting on first-trimester diagnosis of AIP that was subsequently confirmed in the third trimester either during operative delivery or by pathological examination were included. Meta-analysis of proportions, random-effects meta-analysis and hierarchical summary receiver-operating characteristics curve analysis were used to analyze the data.Seven studies, involving 551 pregnancies at high risk of AIP, were included. At least one ultrasound sign suggestive of AIP was detected in 91.4% (95% CI, 85.8-95.7%) of cases with confirmed AIP. The most common ultrasound feature in the first trimester of pregnancy was low implantation of the gestational sac close to a previous uterine scar, which was observed in 82.4% (95% CI, 46.6-99.8%) of cases. Anechoic spaces within the placental mass (lacunae) were observed in 46.0% (95% CI, 10.9-83.7%) and a reduced myometrial thickness in 66.8% (95% CI, 45.2-85.2%) of cases affected by AIP. Pregnancies with a low implantation of the gestational sac had a significantly higher risk of AIP (odds ratio, 19.6 (95% CI, 6.7-57.3)), with a sensitivity and specificity of 44.4% (95% CI, 21.5-69.2%) and 93.4% (95% CI, 90.5-95.7%), respectively.Ultrasound signs of AIP can be present during the first trimester of pregnancy, even before 11 weeks' gestation. Low anterior implantation of the placenta/gestational sac close to or within the scar was the most commonly seen early ultrasound sign suggestive of AIP, although its individual predictive accuracy was not high. Copyright © 2017 ISUOG. Published by John WileySons Ltd.

OBJECTIVE Ultrasound assessment of the relationship between the ectopic gestational sac and the endometrial line (cross-over sign; COS) in Cesarean scar pregnancy (CSP) has been shown to be useful in predicting the evolution of CSP towards different types of abnormally invasive placenta (AIP). The aim of this study was to ascertain whether the COS can be used to predict surgical outcome in women with AIP. METHODS A retrospective analysis was performed of early first-trimester (6-8 weeks' gestation) ultrasound images of women with AIP managed in the third trimester of pregnancy. We hypothesized that assessment of COS may identify cases of AIP at higher risk of intra- or postsurgical morbidity. Outcomes explored were estimated blood loss during surgery, need for and amount of packed red blood cells and fresh frozen plasma units required either during or after surgery, operative time, intrasurgical complications, gestational age at birth, delivery

Objective Advances in prenatal imaging techniques have led to an increase in the diagnosis of Cesarean scar pregnancy (CSP). However, antenatal counseling when CSP is diagnosed is challenging, and current evidence is derived mainly from small series reporting high rates of adverse maternal outcomes. The aim of this study was to ascertain the performance of prenatal ultrasound in predicting the natural history of CSP using a new sonographic sign, the crossover sign (COS). Methods This was a retrospective analysis of early first-trimester (6–8 weeks' gestation) ultrasound images in women with morbidly adherent placenta (MAP) managed in the third trimester of pregnancy. The relationship between the gestational sac of the CSP, anterior uterine wall and Cesarean scar, defined as the COS, was analyzed to determine whether it could predict evolution in these cases. Odds ratios (ORs) were calculated and logistic regression analysis was performed to investigate the association between different types of COS (COS-1, COS-2+ or COS-2–) and the occurrence of MAP. Results Sixty-eight pregnancies with MAP were included. The risk of placenta percreta was significantly higher in pregnancies with COS-1 than in those with COS-2 (OR, 6.67 (95% CI, 1.3–33.3)). When evaluating the two variants of COS-2 separately, the risk of placenta percreta was significantly higher in pregnancies with COS-1 vs COS-2+ (OR, 5.83 (95% CI, 1.1–30.2)) and this risk was even higher when comparing cases with COS-1 vs COS-2– (OR, 12.0 (95% CI, 1.9–75.7)). Logistic regression analysis showed that COS-1 was associated independently with severe forms of MAP, such as placenta percreta and increta (OR, 12.85 (95% CI, 2.0–84.0)), while COS-2+ was associated independently with placenta accreta (OR, 4.37 (95% CI, 1.1–17.0)). Conclusions Ultrasound assessment of the relationship between the gestational sac of a CSP and the endometrial line (the COS) may help to determine whether a CSP will progress towards a less severe form of MAP, amenable to postnatal treatment, and successful pregnancy outcome. Large prospective studies are needed to confirm our findings and elucidate the natural history of this condition. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

OBJECTIVES: To develop a prenatal ultrasound staging system for placenta accreta spectrum (PAS) disorders in women with placenta previa and to evaluate its association with surgical outcome, placental invasion and the clinical staging system for PAS disorders proposed by the International Federation of Gynecology and Obstetrics (FIGO). METHODS: This was a secondary retrospective analysis of prospectively collected data from women with placenta previa. We classified women according to the following staging system for PAS disorders, based upon the presence of ultrasound signs of PAS in women with placenta previa: PAS0, placenta previa with no ultrasound signs of invasion or with placental lacunae but no evidence of abnormal uterus-bladder interface; PAS1, presence of at least two of placental lacunae, loss of the clear zone or bladder wall interruption; PAS2, PAS1 plus uterovescical hypervascularity; PAS3, PAS1 or PAS2 plus evidence of increased vascularity in the inferior part of the lower uterine segment potentially extending into the parametrial region. We explored whether this ultrasound staging system correlates with surgical outcome (estimated blood loss (EBL, mL), units of packed red blood cells (PRBC), fresh frozen plasma (FFP) and platelets (PLT) transfused, operation time (min), surgical complications defined as the occurrence of any damage to the bladder, ureters or bowel, length of hospital stay (days) and admission to intensive care unit (ICU)) and depth of placental invasion. The correlation between the present ultrasound staging system and the clinical grading system proposed by FIGO was assessed. Prenatal and surgical management were not based on the proposed prenatal ultrasound staging system. Linear and multiple regression models were used. RESULTS: Two-hundred and fifty-nine women were included in the analysis. Mean EBL was 516 ± 151 mL in women with PAS0, 609 ± 146 mL in those with PAS1, 950 ± 190 mL in those with PAS2 and 1323 ± 533 mL in those with PAS3, and increased significantly with increasing severity of PAS ultrasound stage. Mean units of PRBC transfused were 0.05 ± 0.21 in PAS0, 0.10 ± 0.45 in PAS1, 1.19 ± 1.11 in PAS2 and 4.48 ± 2.06 in PAS3, and increased significantly with PAS stage. Similarly, there was a progressive increase in the mean units of FFP transfused from PAS1 to PAS3 (0.0 ± 0.0 in PAS1, 0.25 ± 1.0 in PAS2 and 3.63 ± 2.67 in PAS3). Women presenting with PAS3 on ultrasound had significantly more units of PLT transfused (2.37 ± 2.40) compared with those with PAS0 (0.03 ± 0.18), PAS1 (0.0 ± 0.0) or PAS2 (0.0 ± 0.0). Mean operation time was longer in women with PAS3 (184 ± 32 min) compared with those with PAS1 (153 ± 38 min) or PAS2 (161 ± 28 min). Similarly, women with PAS3 had longer hospital stay (7.4 ± 2.1 days) compared with those with PAS0 (3.4 ± 0.6 days), PAS1 (6.4 ± 1.3 days) or PAS2 (5.9 ± 0.8 days). On linear regression analysis, after adjusting for all potential confounders, higher PAS stage was associated independently with a significant increase in EBL (314 (95% CI, 230-399) mL per one-stage increase; P

Although the incidence of morbidly adherent placenta (MAP) has risen progressively in the last two decades, there remains uncertainty about the diagnosis and management of this condition. The aim of this review is to provide up-to-date and evidence-based answers to common clinical questions regarding the diagnosis and management of MAP. Different risk factors have been associated with MAP; however, previous Cesarean section and placenta previa are the most frequently associated. Ultrasound is the primary method for diagnosing MAP and has a good overall diagnostic accuracy for its detection. When considering the different ultrasound signs of MAP, color Doppler seems to provide the best diagnostic performance. Magnetic resonance imaging has the same accuracy in diagnosing MAP as does ultrasound examination; its use should be considered when a resective procedure, such as hysterectomy, is planned as it can provide detailed information about the topography of placental invasion and predict difficulties that may arise in surgery. The optimal gestational age for delivery in pregnancies with MAP is yet to be established; planning surgery between 35 and 36 weeks of gestation provides the best balance between fetal maturity and the risk of unexpected episodes of heavy bleeding, which are more likely to occur with delivery after this timepoint, especially in severe cases of MAP. The optimal surgical approach to MAP depends on multiple factors, including availability of an experienced team, specific surgical skills and hospital resources. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.

OBJECTIVE To ascertain whether the prevalence of ultrasonography signs of abnormally invasive placenta (AIP) changes during pregnancy. METHODS The present retrospective analysis included women with a prenatal diagnosis of AIP that was confirmed at delivery between January 1, 2007, and April 30, 2017, at the Department of Obstetrics and Gynaecology, Arnas Civico Hospital, Palermo, Italy. Ultrasonography signs of AIP were recorded at four different intervals during pregnancy: early first (6-9 weeks), first (11-14 weeks), second (15-24 weeks), and third trimester (25-36 weeks). RESULTS There were 105 pregnancies included. Low implantation of the gestational sac was present on all ultrasonography images from the early first trimester compared with on 23 of 83 (27.7%) images from 11-14 weeks of pregnancy. The identification of loss of the clear space, placental lacunae, bladder wall interruption, and uterovesical hypervascularity all increased (all P

Introduction The aim of this study was to assess the diagnostic accuracy of ultrasound in detecting the depth of abnormally invasive placenta in women at risk. Material and methods Prospective longitudinal study including women with placenta previa and at least one prior cesarean delivery or uterine surgery. Depth of abnormally invasive placenta was defined as the degree of trophoblastic invasion through the myometrium and was assessed with histopathological analysis. The ultrasound signs explored were: loss of clear zone, placental lacunae, bladder wall interruption, uterovesical hypervascularity, and increased vascularity in the parametrial region. Results In all, 210 women were included in the analysis. When using at least one sign, ultrasound had an overall sensitivity of 100% (95% CI 96.5-100) and overall specificity of 61.9 (95% CI 51.9-71.2) for all types of abnormally invasive placenta. Using two ultrasound signs increased the diagnostic accuracy in terms of specificity (100%, 95% CI 96.5-100) but did not affect sensitivity. When stratifying the analysis according to the depth of placental invasion, using at least one sign had a sensitivity of 100% (95% CI 93.7-100) and 100% (95% CI 92.6-100) for placenta accreta/increta and percreta, respectively. Using three ultrasound signs improved the detection rate for placenta percreta with a sensitivity of 100% (95% CI 92.6-100) and a specificity of 77.2% (95% CI 69.9-83.4). Conclusion Ultrasound has a high diagnostic accuracy in detecting the depth of placental invasion when applied to a population with specific risk factors for anomalies such as placenta previa and prior cesarean delivery or uterine surgery.

Objective To demonstrate the efficacy of placement and inflation of Foley balloon catheters prophylactically to prevent, or as an adjuvant therapy to control, bleeding in women undergoing treatment for Cesarean scar pregnancy (CSP) or cervical pregnancy (CxP). Methods This was a retrospective study of 18 women with either CSP (n = 16) or CxP (n = 2), who underwent Foley balloon catheter placement under continuous transvaginal or transabdominal ultrasound guidance to prevent or manage bleeding following treatment, which in most cases comprised local (intragestational sac) and intramuscular (IM) methotrexate (MTX) injections. In eight cases, the balloon catheter was placed immediately following local and/or IM MTX treatment, either because of bleeding or prophylactically; in eight cases, the catheter was placed as part of a two-step protocol, with patients first treated with local and IM MTX injection, then suction aspiration on Day 4 or 5, followed by planned insertion of a balloon catheter; in one patient the balloon was placed on Day 21 after local and IM MTX treatment, due to sudden bleeding; and in one case of a heterotopic pregnancy, one intrauterine and one cervical, the balloon was placed due to severe bleeding. Human chorionic gonadotropin (hCG) levels were evaluated weekly following MTX injection. Results Gestational ages at balloon placement ranged between 5 and 12 + 2 weeks. All embryos/fetuses, with the exception of the cervical heterotopic one, had heart activity and catheter placement was well-tolerated by all women. The balloon tamponade effectively reduced or prevented maternal vaginal bleeding in all except one patient; this woman had a heterotopic CxP and required abdominal robotic cerclage to control the bleeding. Catheters were kept in place for a mean of 3.6 (range, 1–6) days. hCG levels returned to low or zero levels within 19–82 days following MTX injection. Fifteen women required antibiotic treatment following the procedure. One woman with CSP developed an arteriovenous malformation requiring uterine artery embolization. Conclusion Ultrasound-guided placement and inflation of Foley balloon catheters was easy to perform and well-tolerated by patients undergoing treatment for CSP or CxP, and successfully prevented or helped in the management of bleeding complications. Based on our experience and previous publications we suggest having the option of balloon catheter insertion available when local treatment of CSP or CxP is undertaken. Copyright © 2014 ISUOG. Published by John Wiley & Sons Ltd.

Objective To ascertain the impact of prenatal diagnosis on surgical outcome of women affected by abnormally invasive placenta (AIP). Methods MEDLINE, EMBASE, CINAHL and Cochrane databases were searched. Observed outcomes included: gestational age at birth (weeks), amount of blood loss (L), units of red blood cells (RBC), platelets (PLT) and fresh frozen plasma (FFP) transfused, length of stay in hospital and the intensive care unit (ICU) (days), urinary tract injury and infection. Only studies reporting the occurrence of any of the explored outcomes in women with a prenatal compared with an intrapartum diagnosis of AIP were considered eligible for inclusion. Random-effect head-to-head meta-analyses were used to analyze the data. Results Thirteen studies were included. Women with a prenatal diagnosis of AIP had less blood loss during surgery (mean difference (MD), -0.87; 95% CI, -1.5 to -0.23), had fewer units of RBC (MD, -1.45; 95% CI, -2.9 to -0.04) and FFP (MD, -1.73; 95% CI, -3.3 to -0.2) transfused, and delivered earlier (MD, 1.33 weeks; 95% CI, -2.23 to -0.43) compared with those with an intrapartum diagnosis. The risk of admission to an ICU and length of in-hospital and in-ICU stay were not different between the groups. Prenatal diagnosis of AIP was associated with a higher risk of urinary-tract injury (odds ratio, 2.5; 95% CI, 1.3-4.6), mainly due to the higher prevalence of placenta percreta in the group with AIP diagnosed prenatally. Conclusion Prenatal diagnosis of AIP is associated with reduced hemorrhagic morbidity compared with cases in which such anomalies are detected at delivery. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.

Objective To explore the outcome in women managed expectantly following the diagnosis of Cesarean scar pregnancy (CSP). Methods An electronic search of MEDLINE, EMBASE and ClinicalTrials.gov databases was performed utilizing combinations of relevant medical subject headings for 'Cesarean scar pregnancy' and 'outcome'. Reference lists of relevant articles and reviews were hand-searched for additional reports. Observed outcomes included: severe first-trimester vaginal bleeding; clinical symptoms (abdominal pain, vaginal bleeding) requiring treatment; uncomplicated miscarriage; complicated miscarriage requiring intervention; first- or second-trimester uterine rupture or hysterectomy; third-trimester bleeding, uterine rupture or hysterectomy; maternal death; incidence of abnormally invasive placenta (AIP); prevalence of placenta percreta; ultrasound signs suggestive of AIP; and live birth. Meta-analyses of proportions using a random-effects model were used to combine data. Cases were stratified based on the presence or absence of embryonic/fetal heart activity at the time of diagnosis. Results A total of 17 studies (69 cases of CSP managed expectantly, 52 with and 17 without embryonic/fetal heart beat) were included. In women with CSP and embryonic/fetal heart activity, 13.0% (95% CI, 3.8-26.7%) experienced an uncomplicated miscarriage, while 20.0% (95% CI, 7.1-37.4%) required medical intervention. Uterine rupture during the first or second trimester of pregnancy occurred in 9.9% (95% CI, 2.9-20.4%) of cases, while hysterectomy was required in 15.2% (95% CI, 3.6-32.8%) of all cases. Forty (76.9% (95% CI, 65.4-86.5%)) women progressed to the third trimester of pregnancy, of whom 39.2% (95% CI, 15.4-66.2%) experienced severe bleeding. Finally, 74.8% (95% CI, 52.0-92.1%) had a surgical or pathological diagnosis of AIP at delivery and around two-thirds (69.7% (95% CI, 42.8-90.1%)) of them had placenta percreta. In women with CSP but no embryonic/fetal cardiac activity, an uncomplicated miscarriage occurred in 69.1% (95% CI, 47.4-87.1%) of cases, while surgical or medical intervention during or immediately after miscarriage was required in 30.9% (95% CI, 12.9-52.6%). Uterine rupture during the first trimester of pregnancy occurred in 13.4% (95% CI, 2.7-30.3%) of cases, but hysterectomy was not required in any case. Conclusions CSP with positive embryonic/fetal heart activity managed expectantly is associated with a high burden of maternal morbidity including severe hemorrhage, early uterine rupture, hysterectomy and severe AIP. Despite this, a significant proportion of pregnancies complicated by CSP may progress to, or close to, term, thus questioning whether termination of pregnancy should be the only therapeutic option offered to these women. Expectant management of CSP with no cardiac activity may be a reasonable option in view of the low likelihood of maternal complications requiring intervention, although close surveillance is advisable to avoid adverse maternal outcome. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Objective To evaluate outcomes of women undergoing cesarean hysterectomy for abnormal invasive placenta (AIP) with and without preoperative balloon catheter placement in internal iliac arteries. Study design A prospective observational study of women with ultrasound diagnosis of AIP and a planned delivery at our institution. From January 2004 to June 2009, all AIP cases were treated with planned multidisciplinary cesarean hysterectomy alone (CHa group). From July 2009 to September 2013 a pre-operative balloon catheter protocol was introduced (BC group). Statistical analysis considered the entire sample (placenta accreta/increta and percreta) and the individual subgroups (accreta/increta vs percreta). Results Twenty-three cases of AIP (10 accreta/increta and 13 percreta) were treated with cesarean hysterectomy alone, and 30 cases of AIP (12 accreta/increta and 18 percreta) were treated with cesarean hysterectomy and pre-operative balloon catheters. For the entire sample, a significant difference in estimated blood loss and transfused blood products units was observed between CHa group and BC group. When women with placenta accreta/increta and women with placenta percreta were analysed separately, no difference in estimated blood loss and transfused blood products units was found between the BC and the CHa groups in women with placenta accreta/increta. However, in women with placenta percreta, mean estimated blood loss and transfused blood products units were higher in the CHa group compared with BC group (1507 ml vs 933.33 ml; 3.31 units vs 0.67 units). Postoperative recovery differed between the two groups, but no differences were observed in any other outcomes. Conclusions Pre-operative placement of intravascular balloon catheters is a feasible treatment for AIP, and is particularly useful in cases of placenta percreta.

To comment on the prevalence, diagnosis, and treatment of the septate uterus, with special reference to hysteroscopic metroplasty and its effect on reproductive outcome, we searched publications in PubMed and Embase. Original articles, meta-analysis, reviews, and opinion articles were selected. The studies suggest that the prevalence of the septate uterus is increased in women with repeated pregnancy loss and infertility. Reliable diagnosis depends on accurate assessment of the uterine fundal contour and uterine cavity by means of magnetic resonance and three-dimensional ultrasound. Pertinent published data comparing pregnancy outcome before and after hysteroscopic metroplasty indicated a marked improvement after surgery. Magnetic resonance and three-dimensional ultrasound represent the gold standard for diagnosis of septate uterus. Hysteroscopic metroplasty with its simplicity, minimal postoperative sequelae, and improved reproductive outcome is the gold standard for treatment, not only in patients with recurrent pregnancy loss and premature labor but also in patients with infertility, especially if in vitro fertilization is being contemplated.

Objectives To evaluate the diagnostic accuracy of two-dimensional (2D) gray-scale and color Doppler and three-dimensional (3D) power Doppler sonographic criteria for morbidly adherent placenta (MAP), and to identify criteria to help distinguish placenta accreta from placenta percreta. Methods We enrolled 187 patients with placenta previa and history of uterine surgery and performed transabdominal and transvaginal ultrasound examination for early detection of MAP. With 2D gray-scale transabdominal and transvaginal ultrasonography, we investigated loss/irregularity of the echolucent area between the uterus and the placenta (‘clear space’), thinning or interruption of the hyperechoic interface between the uterine serosa and the bladder wall and the presence of turbulent placental lacunae with high-velocity flow (>15 cm/s). Using transabdominal 3D power Doppler, we evaluated the hypervascularity of the uterine serosa–bladder wall interface and irregular intraplacental vascularization. Ultrasound findings were reviewed against the final diagnosis made during Cesarean section (CS). Results MAP was detected on CS in 41 patients. All of them had an anterior placenta previa (34 major and seven minor) and had undergone at least one previous CS. The evaluated sonographic criteria showed good diagnostic performance; in MAP patients at least two out of five criteria were detected, with at most one of the criteria present in patients without MAP. Loss/irregularity of clear space used as a single criterion was responsible for the most false positives, demonstrating a low positive predictive value. Irregular intraplacental vascularization with tortuous confluent vessels affecting the entire width of the placenta, and hypervascularity of the entire uterine serosa–bladder wall interface, were only detected, on 3D power Doppler, in cases of placenta percreta. Conclusions The reviewed ultrasound criteria may be useful for the prenatal diagnosis of MAP and to differentiate between placenta accreta and placenta percreta; 3D power Doppler techniques were an important aid in the diagnosis. Copyright © 2013 ISUOG. Published by John Wiley & Sons, Ltd.

Advances in prenatal imaging techniques have led to an increase in the diagnosis of Cesarean scar pregnancy (CSP). However, antenatal counseling when CSP is diagnosed is challenging, and current evidence is derived mainly from small series reporting high rates of adverse maternal outcomes. The aim of this study was to ascertain the performance of prenatal ultrasound in predicting the natural history of CSP using a new sonographic sign, the crossover sign (COS).This was a retrospective analysis of early first-trimester (6-8 weeks' gestation) ultrasound images in women with morbidly adherent placenta (MAP) managed in the third trimester of pregnancy. The relationship between the gestational sac of the CSP, anterior uterine wall and Cesarean scar, defined as the COS, was analyzed to determine whether it could predict evolution in these cases. Odds ratios (ORs) were calculated and logistic regression analysis was performed to investigate the association between different types of COS (COS-1, COS-2+ or COS-2-) and the occurrence of MAP.Sixty-eight pregnancies with MAP were included. The risk of placenta percreta was significantly higher in pregnancies with COS-1 than in those with COS-2 (OR, 6.67 (95% CI, 1.3-33.3)). When evaluating the two variants of COS-2 separately, the risk of placenta percreta was significantly higher in pregnancies with COS-1 vs COS-2+ (OR, 5.83 (95% CI, 1.1-30.2)) and this risk was even higher when comparing cases with COS-1 vs COS-2- (OR, 12.0 (95% CI, 1.9-75.7)). Logistic regression analysis showed that COS-1 was associated independently with severe forms of MAP, such as placenta percreta and increta (OR, 12.85 (95% CI, 2.0-84.0)), while COS-2+ was associated independently with placenta accreta (OR, 4.37 (95% CI, 1.1-17.0)).Ultrasound assessment of the relationship between the gestational sac of a CSP and the endometrial line (the COS) may help to determine whether a CSP will progress towards a less severe form of MAP, amenable to postnatal treatment, and successful pregnancy outcome. Large prospective studies are needed to confirm our findings and elucidate the natural history of this condition. Copyright © 2016 ISUOG. Published by John WileySons Ltd.

Although the incidence of morbidly adherent placenta (MAP) has risen progressively in the last two decades, there remains uncertainty about the diagnosis and management of this condition. The aim of this review is to provide up-to-date and evidence-based answers to common clinical questions regarding the diagnosis and management of MAP. Different risk factors have been associated with MAP; however, previous Cesarean section and placenta previa are the most frequently associated. Ultrasound is the primary method for diagnosing MAP and has a good overall diagnostic accuracy for its detection. When considering the different ultrasound signs of MAP, color Doppler seems to provide the best diagnostic performance. Magnetic resonance imaging has the same accuracy in diagnosing MAP as does ultrasound examination; its use should be considered when a resective procedure, such as hysterectomy, is planned as it can provide detailed information about the topography of placental invasion and predict difficulties that may arise in surgery. The optimal gestational age for delivery in pregnancies with MAP is yet to be established; planning surgery between 34 and 36 weeks of gestation provides the best balance between fetal maturity and the risk of unexpected episodes of heavy bleeding, which are more likely to occur with delivery after this timepoint, especially in severe cases of MAP. The optimal surgical approach to MAP depends on multiple factors, including availability of an experienced team, specific surgical skills and hospital resources. Copyright © 2015 ISUOG. Published by John WileySons Ltd.

Vascular control is a fundamental step in the surgical management of morbidly adherent placenta (MAP), and this implies a precise knowledge of the vascular supply in the lower part of the genital tract. High degrees of MAP are sometimes characterised by the presence of a rich vascular anastomotic system between the bladder, uterus, and vagina involving the superior, medial, and inferior vaginal and the lower vesical arteries. This brief report shows that prenatal ultrasound assessment of bladder-uterovaginal anastomoses in MAP is feasible.

To demonstrate the efficacy of placement and inflation of Foley balloon catheters prophylactically to prevent, or as an adjuvant therapy to control, bleeding in women undergoing treatment for Cesarean scar pregnancy (CSP) or cervical pregnancy (CxP).This was a retrospective study of 18 women with either CSP (n = 16) or CxP (n = 2), who underwent Foley balloon catheter placement under continuous transvaginal or transabdominal ultrasound guidance to prevent or manage bleeding following treatment, which in most cases comprised local (intragestational sac) and intramuscular (IM) methotrexate (MTX) injections. In eight cases, the balloon catheter was placed immediately following local and/or IM MTX treatment, either because of bleeding or prophylactically; in eight cases, the catheter was placed as part of a two-step protocol, with patients first treated with local and IM MTX injection, then suction aspiration on Day 4 or 5, followed by planned insertion of a balloon catheter; in one patient the balloon was placed on Day 21 after local and IM MTX treatment, due to sudden bleeding; and in one case of a heterotopic pregnancy, one intrauterine and one cervical, the balloon was placed due to severe bleeding. Human chorionic gonadotropin (hCG) levels were evaluated weekly following MTX injection.Gestational ages at balloon placement ranged between 5 and 12 + 2 weeks. All embryos/fetuses, with the exception of the cervical heterotopic one, had heart activity and catheter placement was well-tolerated by all women. The balloon tamponade effectively reduced or prevented maternal vaginal bleeding in all except one patient; this woman had a heterotopic CxP and required abdominal robotic cerclage to control the bleeding. Catheters were kept in place for a mean of 3.6 (range, 1-6) days. hCG levels returned to low or zero levels within 19-82 days following MTX injection. Fifteen women required antibiotic treatment following the procedure. One woman with CSP developed an arteriovenous malformation requiring uterine artery embolization.Ultrasound-guided placement and inflation of Foley balloon catheters was easy to perform and well-tolerated by patients undergoing treatment for CSP or CxP, and successfully prevented or helped in the management of bleeding complications. Based on our experience and previous publications we suggest having the option of balloon catheter insertion available when local treatment of CSP or CxP is undertaken.

a b s t r a c t Objective: To evaluate the efficacy and feasibility of thermo-ablative fractional CO2 laser for the treatment of symptoms related to vulvo-vaginal atrophy (VVA) in post-menopausal women. Methods: From April 2013 to December 2013, post-menopausal patients who complained of one or more VVA-related symptoms and who underwent vaginal treatment with fractional CO2 laser were enrolled in the study. At baseline (T0) and 30 days post-treatment (T1), vaginal status of the women was evaluated using the Vaginal Health Index (VHI), and subjective intensity of VVA symptoms was evaluated using a visual analog scale (VAS). At T1, treatment satisfaction was evaluated using a 5-point Likert scale. Results: During the study period, a total of 48 patients were enrolled. Data indicated a significant improve- ment in VVA symptoms (vaginal dryness, burning, itching and dyspareunia) (P < 0.0001) in patients who had undergone 3 sessions of vaginal fractional CO2 laser treatment. Moreover, VHI scores were sig- nificantly higher at T1 (P < 0.0001). Overall, 91.7% of patients were satisfied or very satisfied with the procedure and experienced considerable improvement in quality of life (QoL). No adverse events due to fractional CO2 laser treatment occurred. Conclusion: Thermo-ablative fractional CO2 laser could be a safe, effective and feasible option for the treatment of VVA symptoms in post-menopausal women.

To evaluate the diagnostic accuracy of two-dimensional (2D) gray-scale and color Doppler and three-dimensional (3D) power Doppler sonographic criteria for morbidly adherent placenta (MAP), and to identify criteria to help distinguish placenta accreta from placenta percreta.We enrolled 187 patients with placenta previa and history of uterine surgery and performed transabdominal and transvaginal ultrasound examination for early detection of MAP. With 2D gray-scale transabdominal and transvaginal ultrasonography, we investigated loss/irregularity of the echolucent area between the uterus and the placenta ('clear space'), thinning or interruption of the hyperechoic interface between the uterine serosa and the bladder wall and the presence of turbulent placental lacunae with high-velocity flow (15 cm/s). Using transabdominal 3D power Doppler, we evaluated the hypervascularity of the uterine serosa-bladder wall interface and irregular intraplacental vascularization. Ultrasound findings were reviewed against the final diagnosis made during Cesarean section (CS).MAP was detected on CS in 41 patients. All of them had an anterior placenta previa (34 major and seven minor) and had undergone at least one previous CS. The evaluated sonographic criteria showed good diagnostic performance; in MAP patients at least two out of five criteria were detected, with at most one of the criteria present in patients without MAP. Loss/irregularity of clear space used as a single criterion was responsible for the most false positives, demonstrating a low positive predictive value. Irregular intraplacental vascularization with tortuous confluent vessels affecting the entire width of the placenta, and hypervascularity of the entire uterine serosa-bladder wall interface, were only detected, on 3D power Doppler, in cases of placenta percreta.The reviewed ultrasound criteria may be useful for the prenatal diagnosis of MAP and to differentiate between placenta accreta and placenta percreta; 3D power Doppler techniques were an important aid in the diagnosis.

In an attempt to clarify the role of gliadin toxicity in the pathogenesis of gluten intolerance (celiac disease), previous in vitro studies have been based on two-dimensional human cell cultures. However, the specific morphological and biochemical properties of in vivo tissue are better maintained in three-dimensional cell cultures (multicellular spheroids, MCS). The aim of this study was to develop a three-dimensional in vitro model to investigate the effects of gliadin on epithelial cells and broaden our understanding of the early tissue damage occurring in celiac disease.The three-dimensionally growing Lovo cell line was exposed to increasing concentrations of peptic-tryptic-digested bread wheat gliadin (from 125 to 1000 microg/mL) for 7 days in order to evaluate cell viability (colony-forming assay), and at the standard concentration of 500 microg/mL for 7 days in order to evaluate MCS diameters, volumes and cell morphology using light and electron microscopy.In comparison with the controls, the cell viability of the gliadin-treated MCS was significantly reduced (20-80%), but there was no difference in size. Various degrees of cell damage (autophagic vacuoles and intra-cytoplasmic lipid-like droplets) were detected by both light and electron microscopy.This is the first study investigating the effects of gliadin on MCS. Lovo MCS seem to be responsive to gliadin exposure, thus confirming previous results obtained using two-dimensional cell cultures. The data suggest that three-dimensional cell cultures may be useful in broadening our understanding of some of the early effects of gliadin peptides on epithelial cells.

The relevant background to the development of engineering ceramics for advanced applications is presented. A number of areas for ceramics in energy production units are considered: heat exchangers, hot gas cleaning, MHD generators, solid electrolyte fuel cells, boilers and gas turbines. Prospects for future markets are good.

The need for better performance, safety and comfort is the driving force behind the dramatic growth in car electronics. The key to success depends mainly on system reliability and cost which in turn are related to the choice of technological approach. The basic topics to be investigated are, on the one hand, system architecture and, on the other, the implementation techniques involved. Large scale integration of a consistent portion of the system will be necessary but other factors such as interconnections, packages and so on must also be taken into account. The variety of boards, components and assembly techniques currently available are just adequate for present needs, but for the 1990s the continuously increasing complexity of automotive electronic systems will probably necessitate better use of what is available and possibly new ideas.

A theoretical investigation about conduction phenomena in metal-dielectric-metal sandwiches is described. It was assumed that the dielectric layer is very thin (less than 100 A, say) and the metals have different electron work functions. The last hypothesis implies a built-in field to be present through the dielectric layer with no applied voltage. Different equations are deduced relating the current density to the applied voltage at different ranges of the applied voltage. The range of validity of each equation is deduced and it is shown that the equations properly overlap at the extremes of their ranges. The considered structures should exhibit peculiar rectification characteristics. In fact it occurs an inversion of the rectification ratio at an applied voltage, which can be correlated to the electron work functions of the metal electrodes, to the electron affinity of the dielectric material and to the dielectric layer thickness. The inversion of the rectification ratio was actually observed byMiles andSmith.