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The aim of the present study was to evaluate the contamination levels of some classes of persistent organic pollutants in free-range hen eggs and to estimate the related human dietary exposure in a site of national interest, characterized by a serious state of environmental pollution in the Bussi sul Tirino area in central Italy. For these purposes, 17 samples of free-range hen eggs collected in home-producing farms located in the site of national interest territory were analyzed for 17 polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs), 12 dioxin-like polychlorinated biphenyls (dl-PCBs), and 6 non–dioxin-like PCBs (ndl-PCBs). Dietary exposure was assessed assuming a standard consumption of eggs per week. The concentration of ∑PCDD/Fs plus dl-PCBs ranged from 0.463 to 8.028 pg toxic equivalent g−1 fat, whereas the mean contamination level of the ∑ndl-PCBs ranged from 0.234 to 7.741 ng toxic equivalent g−1 fat. PCDD/Fs and PCBs contamination levels were lower than maximum values established by the Commission Regulation (European Union) 1259/2011, except for one sample. The estimated weekly intake, calculated to evaluate the contribution in terms of the monitored pollutants of the locally produced eggs to the diet, was lower than the tolerable weekly intake established by the European Food Safety Authority. [ABSTRACT FROM AUTHOR]

Background: An association between oral contraceptive (OC) use and venous thromboembolism (VTE) has long been recognized. However, no summary estimates of the increase in VTE risk associated with OC use have been available since 1995, and no meta-analyses have evaluated the VTE risk of new preparations containing drospirenone.Objective: The aim of the study was to carry out a meta-analysis to summarize existing evidence on the association between venous VTE and OC use, and to investigate how such an association may vary according to the type of OC, OC user characteristics, study characteristics and biases.Methods: Relevant cohort or case-control studies were searched in MEDLINE and other electronic databases up to May 2010, with no language restriction. Data were combined using a generic inverse-variance approach. Meta-regression in addition to stratification was used to explore potential predictors of the summary estimate of risk.Results: Sixteen cohort and 39 case-control studies were included in at least one comparison. Overall, the odds ratio (OR) of OC users versus non-users was 3.41 (95% CI 2.98, 3.92). This estimate was based upon nine cohort studies evaluating approximately 12 000 000 person-years, and 23 case-control studies including approximately 45 000 women. VTE risk for OC users was significantly lower in studies evaluating 'all VTE cases' than in those evaluating 'idiopathic VTE only' (OR 3.09 and 4.94, respectively). Among the carriers of genetic mutations G20210A and Factor V Leiden (FVL), OC users showed a significantly increased VTE risk compared with non-users (OR 1.63; 95% CI 1.01, 2.65, and OR 1.80; 95% CI 1.20, 2.71, respectively). When the newest OCs containing drospirenone were compared with non-drospirenone-containing OCs (except those containing levonorgestrel only), VTE risk did not significantly increase (OR 1.13; 95% CI 0.94, 1.35).Conclusions: This meta-analysis confirms that OC use significantly increases VTE risk. The strength of this association, however, varies according to the generation of OC, type of outcome and presence of a genetic mutation, with ORs ranging from 3 to 5. [ABSTRACT FROM AUTHOR]

Abstract: A systematic review was undertaken to produce an annotated bibliography of meta-analyses in vaccinology and to evaluate their methodological quality. Based on our evaluation using the Oxman and Guyatt index, the methodological quality of the 121 meta-analyses included in this study is not satisfactory. The most frequent limitations include non-comprehensive bibliographic research; bias in the selection of the studies; lack of quality assessment of individual studies; absence of evaluation of heterogeneity among studies and publication bias. The methodological quality significantly increases with the year of publication and with declared financial support, without differences between profit and non-profit support. Meta-analyses with a higher Oxman and Guyatt quality score are more likely to include only randomized trials and to explore appropriately potential sources of heterogeneity. Most of the methodological deficiencies of meta-analyses in vaccinology could be corrected easily, and meta-analysts should improve the methodological quality of their work to maintain their impact on policy decisions. [Copyright &y& Elsevier]

Occupational therapy holds promise to increase quality of life and social functioning in patients with HIV infection. Since 2000 through 2005, we experimented a complex structured intervention including directly administered HAART, psychiatric support and occupational therapy for 14 patients with advanced HIV infection and multiple disabilities, cared for at an Italian home care facility. Social and occupational abilities were evaluated using the Axis V of DMS-IV, as assessed by the Global Assessment of Functioning Scale. Patients' abilities in coping with stressful situations were examined using the Social Dysfunction Rating Scale. Both outcomes were evaluated in interviews at study entrance and yearly thereafter. As compared to baseline, social function mean score significantly increased by 42% after one year of follow-up, and social stress mean score was significantly reduced by 11%. Both outcomes continued to improve constantly during the entire follow-up. Acceptance of the intervention was high, and three patients got outdoor job positions. The findings from this pilot study suggest that occupational therapy could be integrated with success in the treatment of severely disabled patients with advanced HIV infection. Confirmation from further research is required. [ABSTRACT FROM AUTHOR]

A high level of adherence to highly active antiretroviral therapy (HAART) is essential to minimize the risk of treatment failure and HIV disease progression. This cohort study evaluated the prevalence and predictors of long-term adherence with first-line HAART in a hospitalbased unselected sample of HIV patients from central Italy, and examined the association between adherence and virological response or relapse. Between July 1996 and June 2004, 171 patients (67.3% males; mean age, 41.2 years) were followed for at least 24 weeks and up to 8 years. Adherence was measured by patient self-reports and confirmed using pharmacy records. The prevalence of high-level adherence (≥90%) at 6 months was 88.3%; slightly less than 80% at 12 months. The incidence of adherence failure in the sample remained fairly stable until 24 months of follow-up, then it declined about 5% every 6 months. Cox analysis showed that compared to single/separated patients, homeless and married persons were, respectively, 1.95 times more likely and two times less likely to experience adherence failure ( p < 0.05). The adjusted risk of adherence failure among patients who did not suffer drug-related toxicity was 0.57 ( p <0.05). Medication adherence was significantly associated with shorter time to virological response and longer time to relapse. Adherents were 1.69 times more likely to achieve viral suppression and nine times less likely to experience relapse than nonadherents ( p < 0.01). Efforts at improving adherence should be prolonged for at least 24 months. A protective role of marriage for adherence failure is promising but requires confirmation in further research, that should also clarify the exact mechanisms determining the association. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the association between parental smoking during infancy/adolescence and smoking prevalence in older adult women, and to provide a description of smoking and smoking cessation patterns in this subset of the population. Study design: Cross-sectional survey. Methods: Between 1999 and 2001, trained physicians in 11 health agencies throughout the Abruzzo Region, Italy, conducted semi-structured interviews on 9708 women aged 50-70 years attending mammographic screening (overall response rate 89%). Information was corrected on sociodemographic characteristics, smoking habits, parental smoking during their infancy and/or adolescence, and exposure to environmental tobacco smoke (ETS) inside or outside the family. Results and conclusions: The overall prevalence of current smoking was 15.6% (n=1516), and that of former smoking was 13.2%. Women whose parent(s) smoked were more likely to be current smokers, especially if only the mother smoked (adjusted odds ratio 4.27; 95% confidence interval 2.24-8.12). Other factors significantly associated with current smoking in the multivariate analysis were younger age, lower body mass index, higher level of education, unmarried status, and exposure to ETS either inside or outside the family environment. Eighteen percent of all current smokers were non-inhalers, and more than 60% of ex-smokers quit smoking on their first attempt. Our findings expand the existing evidence suggesting that a strong effect of parental conduct on a daughter's smoking behaviour may persist throughout life. Although more research is needed, especially to clarify the role of genetic and environmental factors in determining the mother-child smoking association, our results suggest that intensifying smoking prevention efforts directed at women with children might considerably reduce the risk of ever smoking in future female generations. [ABSTRACT FROM AUTHOR]

The purpose of this study was to evaluate the activity of digastric, sternocleidomastoid, upper trapezius, lower trapezius and cervical muscles in response to maximum voluntary clenching (MVC) of the teeth. Twenty healthy subjects aged 24–31 years were divided into two groups of 10: a resting group and a clenching group. The resting group simply maintained the mandible at rest with teeth apart for two 1-min periods, whereas the clenching group underwent an initial resting period followed after 1-min by a clenching period during which they were required to perform MVC. The electromyography (EMG) responses of each muscle were recorded during all periods, and means and standard deviations of the root mean square EMG were calculated. Within-group and between-group comparisons of EMG activity were made using, respectively, the Sign two-tailed test for two related samples and the Kolmogorov–Smirnov two-tailed test for two independent samples (significance level 0·05). Data indicated a significant increase of EMG activity of the anterior neck muscles (digastric and sternocleidomastoid) during MVC as compared with EMG recorded during resting periods. If confirmed by further research, our findings suggesting an involvement of anterior neck muscles during isometric contraction of the jaw elevator muscles may have clinical implications. [ABSTRACT FROM AUTHOR]

A meta-analysis of randomized and quasi-randomized control trials evaluating influenza vaccination efficacy in healthy adults was carried out to investigate potential sources of heterogeneity among the published studies. The pooled estimates of vaccine efficacy were 22% (95% CI=16–28) for preventing clinically diagnosed cases of influenza and 63% (95% CI=53–71) for preventing laboratory confirmed cases of influenza. These estimates are likely to vary substantially according to the age of the subjects, with vaccine efficacy decreasing significantly with the increase of the mean age of the patients, and to the methodological quality of trials, with low quality trials associated with an overestimation of influenza vaccine efficacy. Some evidence of publication bias was found, particularly when the outcome assessed was clinically diagnosed influenza. Further high-quality clinical trials, designed to facilitate future pooled analyses, are needed to provide definitive answers for policy-makers. [Copyright &y& Elsevier]

Objective: To report the diagnostic accuracy of cell‐free fetal DNA (cfDNA) in detecting fetal chromosomal anomalies in women experiencing miscarriage. Methods: PubMed, MEDLINE, EMBASE and Cochrane databases were searched from inception to June 2024. The inclusion criteria were women experiencing miscarriage (defined as pregnancy loss before 20 weeks of gestation) who underwent cfDNA screening for trisomies 21, 18 and 13, other autosomal aneuploidies, sex‐chromosome aneuploidies and/or copy‐number variants (CNVs). The index test was cfDNA screening for each of the chromosomal anomalies listed. The reference standard was cytogenetic analysis of pregnancy tissue. The quality of the studies was assessed using the revised tool for the quality assessment of diagnostic accuracy studies. Summary estimates of sensitivity, specificity, positive and negative likelihood ratios, and diagnostic odds ratio were computed using the hierarchical summary receiver‐operating‐characteristics model. Results: Seven studies (887 women) were included in the systematic review and meta‐analysis. cfDNA had a sensitivity and specificity of 100% (95% CI, 81.5–100%) and 100% (95% CI, 99.1–100%), respectively, for trisomy 21, 100% (95% CI, 54.1–100%) and 100% (95% CI, 99.0–100%), respectively, for trisomy 18, and 88.9% (95% CI, 51.8–99.7%) and 100% (95% CI, 99.1–100%), respectively, for trisomy 13. The respective values for other autosomal trisomies were 75.8% (95% CI, 65.7–84.2%) and 99.4% (95% CI, 97.9–99.9%), while those for CNVs were 60.0% (95% CI, 14.7–94.7%) and 100% (95% CI, 97.4–100%). Failure of cfDNA testing was reported in 7.3% (95% CI, 5.7–9.2%) of cases. Conclusion: cfDNA has high diagnostic accuracy in detecting fetal trisomies 21, 18 and 13 in women experiencing miscarriage, while its accuracy for other autosomal aneuploidies and CNVs is only moderate. © 2024 International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

An abstract of the conference paper "Tetralogy of Fallot in the fetus: improving diagnostic criteria," by L. Manzoli and colleagues is presented.

Myelodysplastic syndrome (MDS) is an adult hematological disease that evolves into acute myeloid leukemia (AML) in about 30% of the cases. The availability of a highly specific probe moved us to perform in patients affected with MDS/AML, associated with normal karyotype, painting and fluorescence in situ hybridization (FISH) analysis aimed to check the inositide-specific phospholipase C (PI-PLC) ß1 gene, a player in the control of some checkpoints of the cell cycle. Here we present a preliminary observation in which FISH analysis disclosed in a small group of MDS/AML patients with normal karyotype the monoallelic deletion of the PI-PLCß1 gene. On the contrary, PI-PLC ß4, another gene coding for a signaling molecule, located on 20p12.3 at a distance as far as less than 1Mb from PI-PLCß1, is unaffected in MDS patients with the deletion of PI-PLC ß1 gene, hinting at an interstitial deletion. The MDS patients, bearing the deletion, rapidly evolved to AML. The data suggest the possible involvement of PI-PLCß1 in the progression of the disease and pave the way for a larger investigation aimed at identifying a possible high-risk group among MDS patients with a normal karyotype.Leukemia (2004) 18, 1122-1126. doi:10.1038/sj.leu.2403368 Published online 15 April 2004 [ABSTRACT FROM AUTHOR]

There are several versions of the Diagnosis Related Group (DRG) classification systems that are used for case-mix analysis, utilization review, prospective payment, and planning applications. The objective of this study was to assess the adequacy of two of these DRG systems--Medicare DRG and All Patient Refined DRG--to classify neonatal patients. The first part of the paper contains a descriptive analysis that outlines the major differences between the two systems in terms of classification logic and variables used in the assignment process. The second part examines the statistical performance of each system on the basis of the administrative data collected in all public hospitals of the Emilia-Romagna region relating to neonates discharged in 1997 and 1998. The Medicare DRG are less developed in terms of classification structure and yield a poorer statistical performance in terms of reduction in variance for length of stay. This is important because, for specific areas, a more refined system can prove useful at regional level to remove systematic biases in the measurement of case-mix due to the structural characteristics of the Medicare DRGs classification system. [ABSTRACT FROM AUTHOR]

Presents a study that evaluated versions of the Diagnosis Related Group (DRG) classification systems, the Medicare DRG and the All Patient Refined DRG, which are used for planning activities. Differences between the two systems in terms of classification logic and variables used in the assignment process; Statistical performance of each system on the basis of the administrative data collected in the public hospitals of Emilia-Romagna region in Italy; Suggestions for a more refined system in a regional level.

Objective: To report the outcome of fetuses with congenital cytomegalovirus (CMV) infection and normal ultrasound at the time of diagnosis, and to evaluate the rate of an additional anomaly detected only on magnetic resonance imaging (MRI).Methods: Medline, EMBASE, CINAHL and Cochrane databases were searched for studies reporting on the outcome of fetuses with congenital CMV infection. Inclusion criteria were fetuses with confirmed CMV infection and normal ultrasound assessment at the time of the initial evaluation. The outcomes observed were an anomaly detected on a follow-up ultrasound scan, an anomaly detected on prenatal MRI but missed on ultrasound, an anomaly detected on postnatal assessment but missed prenatally, perinatal mortality, symptomatic infection at birth, neurodevelopmental outcome and hearing and visual deficits. Neurodevelopmental outcome was assessed only in cases of isolated CMV infection confirmed at birth. Subgroup analysis was performed according to the trimester in which maternal infection occurred. Random-effects meta-analysis of proportions was used to analyze the data.Results: Twenty-six studies were included, comprising 2603 fetuses with congenital CMV infection, of which 1178 (45.3%) had normal ultrasound at the time of diagnosis and were included in the analysis. The overall rate of an associated central nervous system (CNS) anomaly detected on a follow-up ultrasound scan was 4.4% (95% CI, 1.4-8.8%) (32/523; 15 studies), while the rates of those detected exclusively on prenatal MRI or on postnatal imaging were 5.8% (95% CI, 1.9-11.5%) (19/357; 11 studies) and 3.2% (95% CI, 0.3-9.0%) (50/660; 17 studies), respectively. The rate of an associated extra-CNS anomaly detected on a follow-up ultrasound scan was 2.9% (95% CI, 0.8-6.3%) (19/523; 15 studies), while the rates of those detected exclusively on MRI or on postnatal imaging were 0% (95% CI, 0.0-1.7%) (0/357; 11 studies) and 0.9% (95% CI, 0.3-1.8%) (4/660; 17 studies), respectively. Intrauterine death and perinatal death each occurred in 0.7% (95% CI, 0.3-1.4%) (2/824; 23 studies) of cases. In cases without an associated anomaly detected pre- or postnatally, symptomatic infection was found in 1.5% (95% CI, 0.7-2.7%) (6/548; 19 studies) of infants, the overall rate of a neurodevelopmental anomaly was 3.1% (95% CI, 1.6-5.1%) (16/550; 19 studies), and hearing problems affected 6.5% (95% CI, 3.8-10.0%) (36/550; 19 studies) of children. Subanalyses according to the trimester in which maternal infection occurred were affected by the very small number of included cases and lack of comparison of the observed outcomes in the original studies. Compared with fetuses infected in the second or third trimester, those infected in the first trimester had a relatively higher risk of having an additional anomaly detected on follow-up ultrasound or MRI, abnormal neurodevelopmental outcome and hearing problems.Conclusions: In fetuses with congenital CMV infection in which no anomalies are detected on prenatal ultrasound or MRI, the risk of adverse postnatal outcome is lower than that reported previously in the published literature when not considering the role of antenatal imaging assessment. The results from this review also highlight the potential role of MRI, even in fetuses with no anomalies detected on ultrasound, as an anomaly can be detected exclusively on MRI in about 6% of cases. The findings from this study could enhance prenatal counseling of pregnancies with congenital CMV infection with normal prenatal imaging. © 2020 International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

Objective: To assess the effectiveness of an HPV vaccination programme in reducing the risk of cervical abnormalities identified at subsequent screening. Design: Retrospective cohort study using administrative health data. Setting: General population of Ferrara Province, Italy. Population: Female residents born in 1986–1993 and participating in the organized cervical screening programme in 2011–2018, who were eligible for HPV vaccination in catch‐up cohorts. Methods: Logistic regression to evaluate the potential association between abnormal cervical cytology and one, two, three or at least one dose of HPV vaccine. Main outcome measures: Cervical abnormalities, as predicted by low‐grade or high‐grade cytology, by number of vaccine doses, stratified by age. Results: The sample consisted of 7785 women (mean age 27.5 years, SD 2.3). Overall, 391 (5.0%) were vaccinated with ≥1 dose and 893 (11.5%) had abnormal cytology. Women receiving at least one vaccine dose were significantly less likely to have an abnormal cytology (adjusted odds ratio 0.52; 95% confidence interval 0.34–0.79). Similar results were observed for women receiving a single dose, for both bivalent and quadrivalent vaccines, and applying buffer periods (excluding cytological outcomes within 1 month, 6 months and 1 year of the first dose). Conclusions: In the context of an organised cervical screening programme in Italy, catch‐up HPV vaccination almost halved the risk of cytological abnormalities. Among Ferrara women, vaccination against human papillomavirus halved the risk of screening cervical abnormalities. Among Ferrara women, vaccination against human papillomavirus halved the risk of screening cervical abnormalities. [ABSTRACT FROM AUTHOR]

Objectives: To report the outcome of pregnancies complicated by twin-twin transfusion syndrome (TTTS) according to Quintero stage.Methods: MEDLINE, EMBASE and CINAHL databases were searched for studies reporting the outcome of pregnancies complicated by TTTS stratified according to Quintero stage (I-V). The primary outcome was fetal survival rate according to Quintero stage. Secondary outcomes were gestational age at birth, preterm birth (PTB) before 34, 32 and 28 weeks' gestation and neonatal morbidity. Outcomes are reported according to the different management options (expectant management, laser therapy or amnioreduction) for pregnancies with Stage-I TTTS. Only cases treated with laser therapy were considered for those with Stages-II-IV TTTS and only cases managed expectantly were considered for those with Stage-V TTTS. Random-effects head-to-head meta-analysis was used to analyze the extracted data.Results: Twenty-six studies (2699 twin pregnancies) were included. Overall, 610 (22.6%) pregnancies were diagnosed with Quintero stage-I TTTS, 692 (25.6%) were Stage II, 1146 (42.5%) were Stage III, 247 (9.2%) were Stage IV and four (0.1%) were Stage V. Survival of at least one twin occurred in 86.9% (95% CI, 84.0-89.7%) (456/552) of pregnancies with Stage-I, in 85% (95% CI, 79.1-90.1%) (514/590) of those with Stage-II, in 81.5% (95% CI, 76.6-86.0%) (875/1040) of those with Stage-III, in 82.8% (95% CI, 73.6-90.4%) (172/205) of those with Stage-IV and in 54.6% (95% CI, 24.8-82.6%) (5/9) of those with Stage-V TTTS. The rate of a pregnancy with no survivor was 11.8% (95% CI, 8.4-15.8%) (69/564) in those with Stage-I, 15.0% (95% CI, 9.9-20.9%) (76/590) in those with Stage-II, 18.6% (95% CI, 14.2-23.4%) (165/1040) in those with Stage-III, 17.2% (95% CI, 9.6-26.4%) (33/205) in those with Stage-IV and in 45.4% (95% CI, 17.4-75.2%) (4/9) in those with Stage-V TTTS. Gestational age at birth was similar in pregnancies with Stages-I-III TTTS, and gradually decreased in those with Stages-IV and -V TTTS. Overall, the incidence of PTB and neonatal morbidity increased as the severity of TTTS increased, but data on these two outcomes were limited by the small sample size of the included studies. When stratifying the analysis of pregnancies with Stage-I TTTS according to the type of intervention, the rate of fetal survival of at least one twin was 84.9% (95% CI, 70.4-95.1%) (94/112) in cases managed expectantly, 86.7% (95% CI, 82.6-90.4%) (249/285) in those undergoing laser therapy and 92.2% (95% CI, 84.2-97.6%) (56/60) in those after amnioreduction, while the rate of double survival was 67.9% (95% CI, 57.0-77.9%) (73/108), 69.7% (95% CI, 61.6-77.1%) (203/285) and 80.8% (95% CI, 62.0-94.2%) (49/60), respectively.Conclusions: Overall survival in monochorionic diamniotic pregnancies affected by TTTS is higher for earlier Quintero stages (I and II), but fetal survival rates are moderately high even in those with Stage-III or -IV TTTS when treated with laser therapy. Gestational age at birth was similar in pregnancies with Stages-I-III TTTS, and gradually decreased in those with Stages-IV and -V TTTS treated with laser and expectant management, respectively. In pregnancies affected by Stage-I TTTS, amnioreduction was associated with slightly higher survival compared with laser therapy and expectant management, although these findings may be confirmed only by future head-to-head randomized trials. Copyright © 2020 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

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 Calí 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. [ABSTRACT FROM AUTHOR]

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 < 0.001), units of PRBC transfused (1.74 (95% CI, 1.33-2.15) per one-stage increase; P < 0.001), units of FFP transfused (1.19 (95% CI, 0.61-1.77) per one-stage increase; P < 0.001), units of PLT transfused (1.03 (95% CI, 0.59-1.47) per one-stage increase; P < 0.001), operation time (38.8 (95% CI, 31.6-46.1) min per one-stage increase; P < 0.001) and length of hospital stay (0.83 (95% CI, 0.46-1.27) days per one-stage increase; P < 0.001). On logistic regression analysis, increased severity of PAS was associated independently with surgical complications (odds ratio, 3.14 (95% CI, 1.36-7.25); P = 0.007), while only PAS3 was associated with admission to the ICU (P < 0.001). All women with PAS0 on ultrasound were classified as having Grade-1 PAS disorder according to the FIGO grading system. Conversely, of the women presenting with PAS1 on ultrasound, 64.1% (95% CI, 48.4-77.3%) were classified as having Grade-3, while 35.9% (95% CI, 22.7-51.6%) were classified as having Grade-4 PAS disorder, according to the FIGO grading system. All women with PAS2 were categorized as having Grade-5 and all those with PAS3 as having Grade-6 PAS disorder according to the FIGO system.Conclusion: Ultrasound staging of PAS disorders is feasible and correlates with surgical outcome, depth of invasion and the FIGO clinical grading system. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the potential benefit of interventional radiology (IR) in improving the outcome of women undergoing surgery for a placenta accreta spectrum (PAS) disorder.Methods: MEDLINE, EMBASE and CINAHL databases were searched for studies comparing outcomes of women with a prenatal diagnosis of PAS who underwent an IR procedure before surgery vs those who did not, using a robust collection of terms relating to PAS. The primary outcome was intraoperative estimated blood loss (EBL). Secondary outcomes were the number of transfused units of packed red blood cells (PRBC), fresh frozen plasma (FFP), platelets and cryoprecipitate, operation time, length of hospital stay, EBL ≥ 2.5 L, PRBC transfused ≥ 5 units, surgical complications, bladder or ureteral injury, relaparotomy, infection, disseminated intravascular coagulation, and complications related to endovascular catheter placement. Only studies reporting on the incidence of, or the mean difference in, the observed outcomes in women affected by a PAS disorder who had vs those who did not have an IR procedure before surgery were considered for inclusion. All outcomes were explored in the overall population of women with a prenatally diagnosed PAS disorder and in those undergoing hysterectomy. Quality assessment of each included study was performed using the Risk Of Bias In Non-randomized Studies of Interventions (ROBINS-I) tool. The GRADE methodology was used to assess the quality of the body of retrieved evidence.Results: Fifteen studies (958 women with PAS) were included. In women who underwent IR before surgery, compared with those who did not, mean EBL (mean difference (MD), -1.02 L; 95% CI, -1.60 to -0.43 L; P < 0.001) and the risk of EBL ≥ 2.5 L (odds ratio (OR), 0.18; 95% CI, 0.04-0.78; P = 0.02) were significantly lower. There was no significant difference between the two groups in the other outcomes explored. On subgroup analysis of pregnancies complicated by PAS undergoing hysterectomy, EBL (MD, -0.68 L; 95% CI, -1.24 to -0.12 L; P = 0.02) and the number of transfused FFP units (MD, -1.66; 95% CI, -2.71 to -0.61; P = 0.02) were significantly lower in women who had an endovascular IR procedure compared with controls. Furthermore, women undergoing IR had a significantly lower risk of EBL ≥ 2.5 L (OR, 0.10; 95% CI, 0.02-0.47; P = 0.004). Overall, complications related to the placement of an endovascular catheter occurred in 5.3% (95% CI, 2.6-8.9; I2 , 65.3%) of pregnancies undergoing IR. Overall quality of evidence, as assessed by GRADE, was very low.Conclusions: The current available data provide encouraging evidence that IR procedures may be associated with lower EBL and need for transfusion in pregnancies undergoing surgery for a PAS disorder. However, given the overall very low quality of the evidence, further large studies are needed in order to confirm the beneficial role of IR in improving the outcome of these women. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

Objective: To explore the outcome of fetuses affected by congenital parvovirus B19 (PB19) infection, with or without signs of hydrops on ultrasound.Methods: PubMed, EMBASE and CINAHL databases were searched for studies reporting on prenatal diagnosis and outcome of fetal PB19 infection. The outcomes explored were miscarriage, perinatal death (PND), intrauterine death, neonatal death, spontaneous resolution of hydrops or fetal anemia, need for intrauterine transfusion (IUT), resolution of hydrops or anemia after transfusion, fetal loss following transfusion, abnormal brain scan after birth and abnormal neurodevelopmental outcome. Outcomes were reported according to the presence or absence of signs of hydrops on ultrasound. A subgroup analysis was performed including hydropic and non-hydropic fetuses diagnosed at < 20 weeks and ≥ 20 weeks of gestation. Meta-analyses of proportions and meta-analyses using individual-data random-effects logistic regression were performed to analyze the data.Results: Thirty-five observational studies were included, involving 611 fetuses affected by PB19 infection. The risks of miscarriage (odds ratio (OR), 11.5; 95% CI, 2.7-49.7) and PND (OR, 4.2; 95% CI, 1.6-11.0) were higher in fetuses with PB19 infection presenting, compared with those not presenting, signs of hydrops on ultrasound. In fetuses affected by hydrops, spontaneous resolution of the infection, defined as disappearance of hydrops without need for IUT, occurred in 5.2% (95% CI, 2.5-8.8%) of cases whereas, in the group of fetuses not affected by hydrops, infection resolved in 49.6% (95% CI, 20.7-78.6%) of cases. IUT was performed in 78.7% (95% CI, 66.4-88.8%) of hydropic and in 29.6% (95% CI, 6.0-61.6%) of non-hydropic fetuses affected by congenital PB19 infection and resolution of the infection after IUT occurred in 55.1% (95% CI, 34.0-75.3%) and in 100% (95% CI, 57.3-100%) of cases, respectively. The risk of fetal loss after IUT was higher in fetuses affected compared with those not affected by hydrops (OR, 9.8; 95% CI, 2.8-34.6). The prevalence of abnormal brain imaging was 9.8% (95% CI, 2.5-21.0%) in fetuses affected and 0.0% (95% CI, 0.0-7.0%) in those not affected by hydrops, whilst the corresponding figures for abnormal neurodevelopmental outcome were 9.5% (95% CI, 2.6-20.2) and 0.0% (95% CI, 0.0-7.5), respectively; however, statistical power to assess these outcomes was inadequate due to the small number of included cases.Conclusions: Hydrops is the main determinant of mortality and adverse perinatal outcome in fetuses with PB19 infection. Perinatal outcome in non-hydropic fetuses is generally favorable. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objectives: The primary aim of this systematic review was to explore the strength of association between birth-weight (BW) discordance and perinatal mortality in twin pregnancy. The secondary aim was to ascertain the contribution of gestational age and growth restriction in predicting mortality in growth-discordant twins.Methods: MEDLINE, EMBASE, CINAHL and ClinicalTrials.gov databases were searched. Only studies reporting on the risk of mortality in twin pregnancies affected compared with those not affected by BW discordance were included. The primary outcomes explored were incidence of intrauterine death (IUD), neonatal death (NND) and perinatal death. Outcome was assessed separately for monochorionic (MC) and dichorionic (DC) twin pregnancies. Analyses were stratified according to BW discordance cut-off (≥ 15%, ≥ 20%, ≥ 25% and ≥ 30%) and selected gestational characteristics, including incidence of IUD or NND before and after 34 weeks' gestation, presence of at least one small-for-gestational age (SGA) fetus in the twin pair and both twins being appropriate-for-gestational age. Risk of mortality in the larger vs smaller twin was also assessed. Meta-analyses using individual data random-effects logistic regression and meta-analyses of proportion were used to analyze the data.Results: Twenty-two studies (10 877 twin pregnancies) were included in the analysis. In DC pregnancies, a higher risk of IUD, but not of NND, was observed in twins with BW discordance ≥ 15% (odds ratio (OR) 9.8, 95% CI, 3.9-29.4), ≥ 20% (OR 7.0, 95% CI, 4.15-11.8), ≥ 25% (OR 17.4, 95% CI, 8.3-36.7) and ≥ 30% (OR 22.9, 95% CI, 10.2-51.6) compared with those without weight discordance. For each cut-off of BW discordance explored in DC pregnancies, the smaller twin was at higher risk of mortality compared with the larger one. In MC twin pregnancies, excluding cases affected by twin-twin transfusion syndrome, twins with BW discordance ≥ 20% (OR 2.8, 95% CI, 1.3-5.8) or ≥ 25% (OR 3.2, 95% CI, 1.5-6.7) were at higher risk of IUD, compared with controls. MC pregnancies with ≥ 25% weight discordance were also at increased risk of NND (OR 4.66, 95% CI, 1.8-12.4) compared with those with concordant weight. The risk of IUD was higher when considering discordant pregnancies involving at least one SGA fetus. The overall risk of mortality in MC pregnancies was similar between the smaller and larger twin, except in those with BW discordance ≥ 20%.Conclusion: DC and MC twin pregnancies discordant for fetal growth are at higher risk of IUD but not of NND compared with pregnancies with concordant BW. The risk of IUD in BW-discordant DC and MC twins is higher when at least one fetus is SGA. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

Objective: To explore the outcome of monochorionic twin pregnancies affected by selective intrauterine growth restriction (sIUGR) according to the umbilical artery Doppler pattern of the smaller twin.Methods: An electronic search of MEDLINE, EMBASE, CINAHL and ClinicalTrials.gov databases (2000-2016) was performed. sIUGR was defined as the presence of one twin with an estimated fetal weight and/or abdominal circumference < 10th or < 5th percentile and classified according to the umbilical artery Doppler flow pattern of the smaller twin (Type I: persistently positive; Type II: persistently absent/reversed; Type III: intermittently absent/reversed). Primary outcomes were perinatal mortality, intrauterine death, neonatal death and double fetal loss. Secondary outcomes were neonatal morbidity, including abnormal postnatal brain imaging, intraventricular hemorrhage, periventricular leukomalacia, admission to neonatal intensive care unit and respiratory distress syndrome, deterioration of fetal status, gestational age at delivery and degree of birth-weight discordance. A composite adverse outcome, defined as the presence of any mortality or abnormal brain findings, was also assessed. Quality assessment of the included studies was performed using the Newcastle-Ottawa Scale. A random-effects meta-analysis was used to compute the summary odds ratios (ORs), mean differences (MD) and proportions for the different outcomes.Results: Thirteen studies (610 pregnancies) were included. The risk of perinatal mortality was higher in twins affected by Type II compared with Type I sIUGR (OR, 4.1 (95% CI, 1.6-10.3)), whereas there was no difference among the other variants of growth restriction. Risk of abnormal postnatal brain imaging was significantly higher in twins affected by either Type II (OR, 4.9 (95% CI, 1.9-12.9)) or Type III (OR, 8.2 (95% CI, 2.0-33.1)) sIUGR compared with Type I sIUGR. The risk for neonatal intensive care unit admission was higher in Type II compared with Type I sIUGR (OR, 18.3 (95% CI, 1.0-339.7)). Twin pregnancies affected by Type I sIUGR were delivered at a significantly later gestational age compared with Type II (MD, 2.8 (95% CI, 1.83-3.86) weeks) and Type III (MD, 2.1 (95% CI, 0.97-3.19) weeks). The degree of birth-weight discordance was higher in Type II compared with Type I (MD, 21.6% (95% CI, 9.9-33.2%)) and Type III (MD, 9.3% (95% CI, 3.8-14.9%)) sIUGR.Conclusion: Monochorionic twin pregnancies affected by Type II sIUGR are at a higher risk of perinatal mortality and morbidity compared with Type I. The likelihood of an abnormal outcome is usually not significantly different between sIUGR Types II and III, although the latter has an unpredictable clinical course. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

ABSTRACT Objective To investigate the diagnostic performance of ultrasound in predicting birth-weight ( BW) discordance in twin pregnancy. Methods Electronic databases PubMed, EMBASE and CINAHL were searched using combinations of MeSH terms 'birth weight', 'discordance', 'twins' and 'ultrasound'. Summary estimates of sensitivity, specificity, positive and negative likelihood ratios and diagnostic odds ratios for the predictive accuracy of sonographically estimated fetal-weight ( EFW) discordance and abdominal-circumference ( AC) discordance in predicting BW discordance were computed using hierarchical summary receiver-operating characteristics curves. Results Twenty studies (including 5826 twin pregnancies) were included. EFW discordance ≥ 20% had a sensitivity of 65.4% and specificity of 90.8% in predicting BW discordance ≥ 20%. The predictive performance of ultrasound performed within 1 month, 2 weeks and 3 days before birth was 61.4%, 72.3% and 78.9%, respectively. EFW discordance ≥ 25% had a sensitivity of 57.7% and specificity of 95.2% in predicting BW discordance ≥ 25%. The sensitivity of EFW discordance ≥ 25% detected within 1 month, 2 weeks and 3 days before birth was 60.0%, 75.0% and 60.3%, respectively, while the corresponding values for specificity were 97.7%, 96.2% and 87.3%, respectively. In view of the different cut-offs reported among studies, it was not possible to perform comprehensive data synthesis for each AC discordance cut-off. The optimal diagnostic performance of AC discordance was for prediction of BW discordance ≥ 25%, with a sensitivity of 70.8% and specificity of 86.4%. Conclusion Ultrasound EFW discordance has an overall moderate accuracy in predicting BW discordance in twin pregnancy. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

Objective: To explore the outcomes associated with fetal hepatobiliary cysts.Methods: MEDLINE and EMBASE were searched for studies reporting on outcomes of fetal hepatobiliary cysts. Outcomes observed were resolution/reduction and increase in cyst size, associated congenital anomalies of the biliary tract and liver, abnormal postnatal liver function tests, clinical symptoms, need for surgery, postsurgical complications and predictive accuracy of prenatal ultrasound in identifying correctly hepatobiliary cysts. Meta-analysis of proportions was used to analyze the data.Results: The search identified 1498 articles, and 22 studies (252 fetuses) were included in the systematic review. For fetal hepatic cysts, resolution or reduction in cyst size either pre- or postnatally occurred in 59.3% (95% CI, 30.9-84.7%) of cases, while an increase in cyst size occurred in 8.7% (95% CI, 1.1-22.4%). No case of hepatic cyst had associated malformations of the biliary tract at birth. Clinical symptoms occurred in 14.8% (95% CI, 6.3-26.1%) of cases and, in 5.4% (95% CI, 0.9-13.6%), they were related to the presence of bile obstruction due to compression of the cyst on the biliary tract. No case of hepatic cyst had abnormal liver function at birth. For fetal biliary cysts, resolution or reduction in cyst size occurred in 8.7% (95% CI, 2.7-17.5%) of cases and an increase in size occurred in 34.4% (95% CI, 20.5-49.8%). Congenital anomalies of the biliary tract and liver, such as fibrosis, occurred in 21.5% (95% CI, 10.2-35.6%) and 17.4% (95% CI, 5.4-34.4%) of cases, respectively. 57.3% (95% CI, 33.9-79.0%) of cases showed impairment in liver function after birth, while 55.0% (95% CI, 37.5-71.9%) showed clinical symptoms, mainly due to bile obstruction (47.9% (95% CI, 29.4-66.7%)). Postsurgical complications occurred in 10.9% (95% CI, 3.7-21.3%) of operated cases. Risk assessment according to different cut-offs of cyst size could not be performed in view of the very small number of included studies.Conclusions: Fetal hepatic cysts are benign, with a low likelihood of associated anomalies of the hepatobiliary tract, abnormal liver function or clinical symptoms. Congenital biliary cysts are associated with a high rate of progression, abnormal liver function after birth and clinical symptoms. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

ABSTRACT: Objective: To explore the outcome of fetuses with a prenatal diagnosis of ovarian cyst. Methods: The electronic databases MEDLINE and EMBASE were searched using keywords and word variants for ‘ovarian cysts’, ‘ultrasound’ and ‘outcome’. The following outcomes in fetuses with a prenatal diagnosis of ovarian cyst were explored: resolution of the cyst, change of ultrasound pattern of the cyst, occurrence of ovarian torsion and intracystic hemorrhage, need for postnatal surgery, need for oophorectomy, accuracy of prenatal ultrasound examination in correctly identifying ovarian cyst, type of ovarian cyst at histopathological analysis and intrauterine treatment. Meta‐analyses using individual data random‐effects logistic regression and meta‐analyses of proportions were performed. Quality assessment of the included studies was performed using the Newcastle–Ottawa Scale. Results: Thirty‐four studies (954 fetuses) were included. In 53.8% (95% CI, 46.0–61.5%) of cases for which resolution of the cyst was evaluated (784 fetuses), the cyst regressed either during pregnancy or after birth. The likelihood of resolution was significantly lower in complex vs simple cysts (odds ratio (OR), 0.15 (95% CI, 0.10–0.23)) and in cysts measuring ≥ 40 mm vs < 40 mm (OR, 0.03 (95% CI, 0.01–0.06)). Change in ultrasound pattern of the cyst was associated with an increased risk of ovarian loss (surgical removal or autoamputation) (pooled proportion, 57.7% (95% CI, 42.9–71.8%)). The risk of ovarian torsion was significantly higher for cysts measuring ≥ 40 mm compared with < 40 mm (OR, 30.8 (95% CI, 8.6–110.0)). The likelihood of having postnatal surgery was higher in patients with cysts ≥ 40 mm compared with < 40 mm (OR, 64.4 (95% CI, 23.6–175.0)) and in complex compared with simple cysts, irrespective of cyst size (OR, 14.6 (95% CI, 8.5–24.8)). In cases undergoing prenatal aspiration of the cyst, rate of recurrence was 37.9% (95% CI, 14.8–64.3%), ovarian torsion and intracystic hemorrhage were diagnosed after birth in 10.8% (95% CI, 4.4–19.7%) and 12.8% (95% CI, 3.8–26.0%), respectively, and 21.8% (95% CI, 0.9–40.0%) had surgery after birth. Conclusion: Size and ultrasound appearance are the major determinants of perinatal outcome in fetuses with ovarian cysts. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

Objective: To explore the outcome of fetuses with a prenatal diagnosis of ovarian cyst.Methods: The electronic databases MEDLINE and EMBASE were searched using keywords and word variants for 'ovarian cysts', 'ultrasound' and 'outcome'. The following outcomes in fetuses with a prenatal diagnosis of ovarian cyst were explored: resolution of the cyst, change of ultrasound pattern of the cyst, occurrence of ovarian torsion and intracystic hemorrhage, need for postnatal surgery, need for oophorectomy, accuracy of prenatal ultrasound examination in correctly identifying ovarian cyst, type of ovarian cyst at histopathological analysis and intrauterine treatment. Meta-analyses using individual data random-effects logistic regression and meta-analyses of proportions were performed. Quality assessment of the included studies was performed using the Newcastle-Ottawa Scale.Results: Thirty-four studies (954 fetuses) were included. In 53.8% (95% CI, 46.0-61.5%) of cases for which resolution of the cyst was evaluated (784 fetuses), the cyst regressed either during pregnancy or after birth. The likelihood of resolution was significantly lower in complex vs simple cysts (odds ratio (OR), 0.15 (95% CI, 0.10-0.23)) and in cysts measuring ≥ 40 mm vs < 40 mm (OR, 0.03 (95% CI, 0.01-0.06)). Change in ultrasound pattern of the cyst was associated with an increased risk of ovarian loss (surgical removal or autoamputation) (pooled proportion, 57.7% (95% CI, 42.9-71.8%)). The risk of ovarian torsion was significantly higher for cysts measuring ≥ 40 mm compared with < 40 mm (OR, 30.8 (95% CI, 8.6-110.0)). The likelihood of having postnatal surgery was higher in patients with cysts ≥ 40 mm compared with < 40 mm (OR, 64.4 (95% CI, 23.6-175.0)) and in complex compared with simple cysts, irrespective of cyst size (OR, 14.6 (95% CI, 8.5-24.8)). In cases undergoing prenatal aspiration of the cyst, rate of recurrence was 37.9% (95% CI, 14.8-64.3%), ovarian torsion and intracystic hemorrhage were diagnosed after birth in 10.8% (95% CI, 4.4-19.7%) and 12.8% (95% CI, 3.8-26.0%), respectively, and 21.8% (95% CI, 0.9-40.0%) had surgery after birth.Conclusion: Size and ultrasound appearance are the major determinants of perinatal outcome in fetuses with ovarian cysts. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

Objectives: Diagnosis of isolated posterior fossa anomalies in children is biased by the fact that only those that are symptomatic are brought to the attention of the appropriate clinical personnel, and the reported rate is often affected by the adoption of different nomenclature, diagnostic criteria, outcome measures, duration of follow-up and neurodevelopmental tools. The aim of this systematic review was to explore the neurodevelopmental outcome of fetuses with a prenatal diagnosis of isolated posterior fossa anomalies.Methods: MEDLINE and EMBASE were searched electronically, utilizing combinations of the relevant medical subject heading terms for 'posterior fossa' and 'outcome'. Studies assessing the neurodevelopmental outcome in children with a prenatal diagnosis of isolated posterior fossa malformations were considered eligible. The posterior fossa anomalies analyzed included Dandy-Walker malformation (DWM), mega cisterna magna (MCM), Blake's pouch cyst (BPC) and vermian hypoplasia (VH). Two authors reviewed all abstracts independently. Quality assessment of the included studies was performed using the Newcastle-Ottawa Scale for cohort studies. Meta-analyses of proportions were used to combine data, and between-study heterogeneity was explored using the I(2) statistic.Results: A total of 1640 articles were identified; 95 were assessed for eligibility and a total of 16 studies were included in the systematic review. The overall rate of abnormal neurodevelopmental outcome in children with a prenatal diagnosis of DWM was 58.2% (95% CI, 21.8-90.0%) and varied from 0-100%. In those with a prenatal diagnosis of MCM, the rate of abnormal neurodevelopmental outcome was 13.8% (95% CI, 7.3-21.9%), with a range of 0-50%. There was no significant association between BPC and the occurrence of abnormal neurodevelopmental delay, with a rate of 4.7% (95% CI, 0.7-12.1%) and range of 0-5%. Although affected by the very small number of studies, there was a non-significant occurrence of abnormal neurodevelopmental delay in children with a prenatal diagnosis of VH, with a rate of 30.7% (95% CI, 0.6-79.1%) and range of 0-100%.Conclusions: Fetuses diagnosed with isolated DWM are at high risk of abnormal neurodevelopmental outcome, while isolated MCM or BPC have a generally favorable outcome. The risk of abnormal developmental delay in cases with isolated VH needs to be further assessed. In view of the wide heterogeneity in study design, time of follow-up, neurodevelopmental tests used and the very small number of included cases, further future large prospective studies with standardized and objective protocols for diagnosis and follow-up are needed in order to ascertain the rate of abnormal neurodevelopmental outcome in children with isolated posterior fossa anomalies. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

Objective: To explore the outcome in fetuses with prenatal diagnosis of posterior fossa anomalies apparently isolated on ultrasound imaging.Methods: MEDLINE and EMBASE were searched electronically utilizing combinations of relevant medical subject headings for 'posterior fossa' and 'outcome'. The posterior fossa anomalies analyzed were Dandy-Walker malformation (DWM), mega cisterna magna (MCM), Blake's pouch cyst (BPC) and vermian hypoplasia (VH). The outcomes observed were rate of chromosomal abnormalities, additional anomalies detected at prenatal magnetic resonance imaging (MRI), additional anomalies detected at postnatal imaging and concordance between prenatal and postnatal diagnoses. Only isolated cases of posterior fossa anomalies - defined as having no cerebral or extracerebral additional anomalies detected on ultrasound examination - were included in the analysis. Quality assessment of the included studies was performed using the Newcastle-Ottawa Scale for cohort studies. We used meta-analyses of proportions to combine data and fixed- or random-effects models according to the heterogeneity of the results.Results: Twenty-two studies including 531 fetuses with posterior fossa anomalies were included in this systematic review. The prevalence of chromosomal abnormalities in fetuses with isolated DWM was 16.3% (95% CI, 8.7-25.7%). The prevalence of additional central nervous system (CNS) abnormalities that were missed at ultrasound examination and detected only at prenatal MRI was 13.7% (95% CI, 0.2-42.6%), and the prevalence of additional CNS anomalies that were missed at prenatal imaging and detected only after birth was 18.2% (95% CI, 6.2-34.6%). Prenatal diagnosis was not confirmed after birth in 28.2% (95% CI, 8.5-53.9%) of cases. MCM was not significantly associated with additional anomalies detected at prenatal MRI or detected after birth. Prenatal diagnosis was not confirmed postnatally in 7.1% (95% CI, 2.3-14.5%) of cases. The rate of chromosomal anomalies in fetuses with isolated BPC was 5.2% (95% CI, 0.9-12.7%) and there was no associated CNS anomaly detected at prenatal MRI or only after birth. Prenatal diagnosis of BPC was not confirmed after birth in 9.8% (95% CI, 2.9-20.1%) of cases. The rate of chromosomal anomalies in fetuses with isolated VH was 6.5% (95% CI, 0.8-17.1%) and there were no additional anomalies detected at prenatal MRI (0% (95% CI, 0.0-45.9%)). The proportions of cerebral anomalies detected only after birth was 14.2% (95% CI, 2.9-31.9%). Prenatal diagnosis was not confirmed after birth in 32.4% (95% CI, 18.3-48.4%) of cases.Conclusions: DWM apparently isolated on ultrasound imaging is a condition with a high risk for chromosomal and associated structural anomalies. Isolated MCM and BPC have a low risk for aneuploidy or associated structural anomalies. The small number of cases with isolated VH prevents robust conclusions regarding their management from being drawn. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

Objectives: The introduction of fetoscopic laser surgery of placental anastomoses has led to a significant improvement of perinatal outcome of twin pregnancies affected by twin-to-twin-transfusion syndrome (TTTS). To quantify the perinatal outcome and neurological morbidity in triplet pregnancies complicated by TTTS, which were treated with fetoscopic laser surgery.Search Strategy: Medline, Embase, Cinahl and Cochrane were searched.Selection Criteria: The outcomes observed were: fetal and perinatal survival, preterm birth and abnormal neurological outcome.Data Collection and Analysis: Two authors reviewed all abstracts independently. Meta-analyses of proportions were used to combine data.Main Results: Eight studies (126 triplet pregnancies, 104 dichorionic-triamniotic [DCTA] and 22 monochorionic-triamniotic [MCTA]) treated with fetoscopic laser surgery were included in this review. In DCTA and MCTA pregnancies, fetal losses were 18.9% and 28.9%, respectively; perinatal losses were 23.6% and 75.0%; preterm births <28 weeks of gestation were 16.9% and 37.1%; preterm births <32 weeks of gestation were 50.0% and 69.5%; at least one fetus survived in 95.4% and 88.9% of the pregnancies; at least two fetuses survived in 81.8% and 68.3% of the pregnancies; and in 55.9% and 48.4% pregnancies all triplets survived. Finally, the incidence of abnormal neurological outcomes ranged from 0 to 37% in DCTA and from 0 to 50% in MCTA triplets.Conclusions: Both DTCA and MCTA triplet pregnancies affected by TTTS are at high risk of adverse perinatal outcome.Tweetable Abstract: Both DTCA and MCTA triplet pregnancies affected by TTTS are at high risk of adverse perinatal outcome. [ABSTRACT FROM AUTHOR]

ABSTRACT Objective The accuracy of prenatal ultrasound examination in detecting jejunal and ileal atresia has been reported in the literature to be highly variable, at 25-90%. The aim of this systematic review was to evaluate the accuracy of prenatal ultrasound in detecting non-duodenal small bowel atresia ( ND-SBA). Methods MEDLINE, EMBASE and The Cochrane Library, including The Cochrane Database of Systematic Reviews ( CDSR), Database of Abstracts of Reviews of Effects ( DARE) and The Cochrane Central Register of Controlled Trials ( CENTRAL), were searched electronically. The overall detection rate of jejunal or ileal atresia using ultrasound was reported. The accuracy of using polyhydramnios and dilated loops of bowel as diagnostic signs was also explored. Results Sixteen studies involving 640 fetuses were included in this review. The detection rate of ND-SBA by prenatal ultrasound was highly variable, with values ranging from 10 to 100%, with an overall prediction of 50.6% (95% CI, 38.0-63.2%). When analyzed separately, the detection rates of jejunal and ileal atresia were 66.3%, (95% CI, 33.9-91.8%) and 25.9% (95% CI, 4.0-58.0%), respectively. Both dilated loops of bowel and polyhydramnios as diagnostic signs for ND-SBA provided a low overall detection rate. Conclusions The diagnostic performance of prenatal ultrasound in identifying ND-SBA is extremely variable. Large studies are needed in order to identify objective and combined criteria for the diagnosis of these anomalies. Copyright © 2014 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

Background and purpose Akinetic crisis ( AC) is the most severe and possibly lethal complication of parkinsonism. It occurs with an incidence of 3‰ Parkinson's disease patients per year, but it is not known whether genetically determined parkinsonism is more or less susceptible to this complication. Methods In a cohort of 756 parkinsonian patients the incidence and outcome of AC was prospectively assessed. A total of 142 of the parkinsonian patients were tested for genetic mutations because of familial parkinsonism, and 20 patients resulted positive: in four the mutation definitely involved mitochondrial functions ( POLG1, PINK1), two presented with LRRK2 mutation, nine presented with GBA mutation and five presented with Park 4 different mutations. Results Akinetic crisis occurred in 30 patients for an incidence of 2.8‰ persons/year and was lethal in seven (23%), not dissimilarly from known incidences of this complication. Yet six of 30 patients were carriers of genetic mutations, one GBA, one LRRK2, one POLG1 and three PINK1. In POLG1 and PINK1 carriers, the syndrome was recurrent and was fatal in three. Incidence of AC was 3.0‰ in familiar parkinsonism, 21.2‰ in genetic parkinsonisms. Conclusions Our preliminary findings suggest that the incidence of AC is remarkably increased in carriers of these genetic mutations. [ABSTRACT FROM AUTHOR]

ABSTRACT Objective To assess systematically the performance of prenatal magnetic resonance imaging ( MRI) in diagnosing the presence, degree and topography of disorders of invasive placentation and to explore the role of the different MRI signs in predicting these disorders. The diagnostic accuracy of ultrasound and MRI in the detection of invasive placentation was also compared. Methods MEDLINE, EMBASE, CINAHL and The Cochrane Library, including The Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects and The Cochrane Central Register of Controlled Trials, were searched electronically utilizing combinations of the relevant medical subject heading terms, keywords and word variants for 'invasive placentation' and 'magnetic resonance imaging'. Only prospective studies reporting a diagnosis of invasive placentation at the time of MRI and retrospective studies in which the radiologist was blinded to the final results were included in the analysis. The MRI signs explored were: uterine bulging, heterogeneous signal intensity, dark intraplacental bands on T2 weighted sequences, focal interruption of the myometrium and tenting of the bladder. Summary estimates of sensitivity, specificity, positive and negative likelihood ratios ( LR+, LR-) and diagnostic odds ratio ( DOR) were based, depending on the number of studies, upon DerSimonian-Laird random-effect or hierarchical summary receiver-operating characteristics models. Results A total of 18 studies involving 1010 pregnancies at risk for invasive placentation were included. The overall diagnostic accuracy of MRI in detecting the presence of invasive placentation was: sensitivity, 94.4% (95% CI, 86.0-97.9%); specificity, 84.0% (95% CI, 76.0-89.8%); LR+, 5.91 (95% CI, 3.73-9.39); LR-, 0.07 (95% CI, 0.02-0.18); DOR, 89.0 (95% CI, 22.8-348.1). MRI had a high predictive accuracy in assessing both the depth and topography of placental invasion. All five MRI signs showed good predictive accuracy in the diagnosis of disorders of invasive placentation. There was no difference in either the sensitivity ( P = 0.24) or the specificity ( P = 0.91) between ultrasound and MRI for the detection of invasive placentation. Conclusions Prenatal MRI is highly accurate in diagnosing disorders of invasive placentation. Ultrasound and MRI have comparable predictive accuracy. Large population-based studies are needed in order to assess whether ultrasound can predict the depth and topography of placental invasion as reliably as can MRI. Copyright © 2014 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

Background: Many strategies have been evaluated to improve the prevention and control of cardiovascular (CVD) risk factors. Nursing telephonic and tele-counseling individualized lifestyle educational programs have been found to improve blood pressure control and adherence to lifestyle recommendation. This study tested the efficacy of a nurse-led reminder program through email (NRP-e) to improve CVD risk factors among hypertensive adults. Methods: All participants received usual CVD prevention and a guideline-based educational program. Subjects in the NRP-e group also received weekly email alerts and phone calls from a nurse care manager for 6 months. Emails contained a reminder program on the need for adherence with a healthy lifestyle based upon current guidelines. Follow-up visits were scheduled at 1, 3 and 6 months after enrollment; randomization was made centrally and blood samples were evaluated into a single laboratory. Results: The final sample consisted of 98 (control) and 100 (NRP-e) subjects (mean age 59.0 ± 14.5 years; 51.0% males). After 6 months, the following CVD risk factors significantly improved in both groups: body mass index, alcohol and fruit consumption, cigarette smoking, adherence to therapy hours, systolic and diastolic blood pressure, fasting blood glucose, low-density lipoproteins (LDL) and total cholesterol, triglycerides, and physical activity. In the NRP-e group, however, the prevalence of several behaviors or conditions at risk decreased significantly more than in the control group: obesity (-16%), low fruit consumption (-24%), uncontrolled hypertension (-61%), LDL (-56%), and total cholesterol (-40%). Conclusions: The NRP-e improved a range of CVD risk factors. The program had low costs, required only an average of <20 min per day in addition to normal practice, and may deserve further evaluation for the inclusion among existing care management approaches. [ABSTRACT FROM AUTHOR]

Inositide signaling pathways can have a role in the Myelodysplastic Syndromes (MDS) progression to acute myeloid leukemia. Erythropoietin (EPO) is currently used in low-risk MDS, where it successfully corrects anemia in 50-70% of patients. However, some MDS patients are refractory to this treatment and little is known about the exact molecular mechanisms underlying the effect of EPO in these subjects. Here, we investigated the role of inositide pathways in low-risk MDS treated with EPO, mainly focusing on the Akt/PI-PLC (Phosphoinositide-Phospholipase C) gamma1 axis, which is activated by the EPO receptor, and PI-PLCbeta1/Cyclin D3 signaling, as Cyclin D3 is associated with hematopoietic proliferation and differentiation. Interestingly, EPO responder patients showed a specific activation of both the Akt/PI-PLCgamma1 pathway and beta-Globin gene expression, while nonresponders displayed an increase in PI-PLCbeta1 signaling. Moreover, in normal CD34+ cells induced to erythroid differentiation, PI-PLCbeta1 overexpression abrogated both EPO-induced Akt phosphorylation and beta-Globin expression. Overall, these findings suggest that PI-PLCbeta1 can act as a negative regulator of erythroid differentiation and confirm the involvement of Akt/PI-PLCgamma1 pathway in EPO signaling, therefore contributing to the comprehension of the effect of EPO in low-risk MDS and possibly paving the way to the identification of MDS patients at higher risk of refractoriness to EPO treatment. [ABSTRACT FROM AUTHOR]

Polycystic ovary syndrome (PCOS) recently has been identified as a risk factor associated with type 2 diabetes. However, the evidence derives from cross-sectional observational studies, retrospective studies, or short-term prospective studies. This long-term prospective study of a large cohort of women with PCOS, followed from youth to middle age, aimed at estimating, for the first time, the incidence and potential predictors of type 2 diabetes in this population. A total of 255 women with PCOS were followed for at least 10 years (mean follow-up 16.9 years). Six women were patients with diabetes at baseline, and another 42 women developed type 2 diabetes during the follow-up. The incidence rate of type 2 diabetes in the study population was 1.05 per 100 person-years. The age-standardized prevalence of diabetes at the end of follow-up was 39.3%, which is significantly higher with respect to that of the general Italian female population of a similar age (5.8%). The likelihood of developing type 2 diabetes significantly increased as BMI, fasting glucose, and glucose area under the curve at baseline increased and significantly decreased as sex hormone-binding globulin (SHBG) levels at follow-up increased. This study demonstrates that the risk of type 2 diabetes is markedly elevated in middle-aged women with PCOS and suggests including BMI, glucose, and SHBG-circulating levels in the risk stratification. [ABSTRACT FROM AUTHOR]

Phosphoinositide-phospholipase C (PI-PLC) beta1 can be considered a specific target for demethylating therapy in high-risk myelodysplastic syndrome (MDS) patients, as azacitidine treatment has been associated with a PI-PLCbeta1-specific promoter demethylation, and induction of PI-PLCbeta1 gene and protein expression. However, little is known about the molecular effect of azacitidine in low-risk MDS or the functional mechanisms linked with azacitidine effect on PI-PLCbeta1 promoter. In the present study, we further investigated the role of epigenetic regulation of PI-PLCbeta1, mainly focusing on the structure of the PI-PLCbeta1 promoter. We first examined the effect of azacitidine on PI-PLCbeta1 promoter methylation and gene expression in low-risk MDS. Moreover, we studied the expression of key molecules associated with the nuclear inositide signaling pathways, such as cyclin D3. By applying a chromatin immunoprecipitation method, we also studied the correlation between the demethylating effect of azacitidine and the degree of recruitment to PI-PLCbeta1 promoter of some transcription factors implicated in hematopoietic stem cell proliferation and differentiation, as well as of the methyl-CpG-binding domain proteins, which specifically interact with methylated DNA. Taken together, our results hint at a specific involvement of PI-PLCbeta1 in epigenetic mechanisms, and are particularly consistent with the hypothesis of a role for PI-PLCbeta1 in azacitidine-induced myeloid differentiation. [ABSTRACT FROM AUTHOR]

Summary: Aims of the study: Earlier P300 studies were conducted when the prevalence of dementia with Lewy Bodies (DLB) was unknown. Our study aims to examine whether P300 abnormalities are present in DLB and to evidence possible differences between DLB and Alzheimer''s disease (AD). A second aim of this study is to look for correlations between P300 recordings and EEG, as abnormal EEG variability has been described in DLB. Patients and methods: Auditory P300 responses were recorded by a classic oddball paradigm in 50 controls, in 36 DLB patients, and in 40 AD patients with MMSE > 20. Results: Reliable auditory P300 responses were obtained in 26 DLB (72%), 33 AD (82.5%), and 46 controls (92%). P300 was more delayed and had lower amplitude in DLB compared to AD groups. P300 topography was also different as the anterior-to-posterior scalp amplitude gradient was reversed in DLB. P300 latency correlated with neuropsychological test scores and with EEG variables. Gradient inversion and delayed P300 responses in frontal derivations evidenced differences between DLB and AD patients with a sensitivity of 70% and a specificity of 97%. Conclusions: P300 recordings are abnormal in DLB and can be useful to distinguish DLB from AD. [Copyright &y& Elsevier]

Apart from the lipids present in the nuclear envelope, the nucleus also contains lipids which are located further inside and are resistant to treatment with nonionic detergents. Evidence is being accumulated on the importance of internal nuclear lipid metabolism. Nuclear lipid metabolism gives rise to several lipid second messengers that function within the nucleus. Moreover, it is beginning to emerge that nuclear lipids not only act as precursors of bioactive second messengers but may be directly involved in regulation of nuclear structure and gene expression. Over the last 10years, especially the role of the inositol lipid cycle in nuclear signal transduction has been extensively studied. This cycle is activated following a variety of stimuli and is regulated independently from the inositide cycle located at the plasma membrane. However, the nucleus contain other lipids, such as phosphatidylcholine, sphingomyelin, fatty acids and eicosanoids. There are numerous reports which suggest that these classes of nuclear lipids may play roles in the nucleus as important as those of phosphoinositides. This review aims at highlighting the most important aspects regarding the metabolism and signaling activities of nuclear phosphatidylcholine, sphingomyelin, fatty acids and eicosanoids. [ABSTRACT FROM AUTHOR]

It is now well established that the reduced capacity of tumor cells of undergoing cell death through apoptosis plays a key role both in the pathogenesis of cancer and in therapeutic treatment failure. Indeed, tumor cells frequently display multiple alterations in signal transduction pathways leading to either cell survival or apoptosis. In mammals, the pathway based on phosphoinositide 3-kinase (PI3K)/Akt conveys survival signals of extreme importance and its downregulation, by means of pharmacological inhibitors of PI3K, considerably lowers resistance to various types of therapy in solid tumors. We recently described an HL60 leukemia cell clone (HL60AR cells) with a constitutively active PI3K/Akt pathway. These cells were resistant to multiple chemotherapeutic drugs, all-trans-retinoic acid (ATRA), and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). Treatment with two pharmacological inhibitors of PI3K, wortmannin and Ly294002, restored sensitivity of HL60AR cells to the aforementioned treatments. However, these inhibitors have some drawbacks that may severely limit or impede their clinical use. Here, we have tested whether or not a new selective Akt inhibitor, 1L-6-hydroxymethyl-chiro-inositol 2(R)-2-O-methyl-3-O-octadecylcarbonate (Akt inhibitor), was as effective as Ly294002 in lowering the sensitivity threshold of HL60 cells to chemotherapeutic drugs, TRAIL, ATRA, and ionizing radiation. Our findings demonstrate that, at a concentration which does not affect PI3K activity, the Akt inhibitor markedly reduced resistance of HL60AR cells to etoposide, cytarabine, TRAIL, ATRA, and ionizing radiation. This effect was likely achieved through downregulation of expression of antiapoptotic proteins such as c-IAP1, c-IAP2, cFLIPL, and of Bad phosphorylation on Ser 136. The Akt inhibitor did not influence PTEN activity. At variance with Ly294002, the Akt inhibitor did not negatively affect phosphorylation of protein kinase C-? and it was less effective in downregulating p70S6 kinase (p70S6K) activity. The Akt inhibitor increased sensitivity to apoptotic inducers of K562 and U937, but not of MOLT-4, leukemia cells. Overall, our results indicate that selective Akt pharmacological inhibitors might be used in the future for enhancing the sensitivity of leukemia cells to therapeutic treatments that induce apoptosis or for overcoming resistance to these treatments.Leukemia (2003) 17, 1794-1805. doi:10.1038/sj.leu.2403044 [ABSTRACT FROM AUTHOR]

TRAIL is a member of the tumor necrosis factor superfamily which induces apoptosis in cancer but not in normal cells. Akt1 promotes cell survival and blocks apoptosis. The scope of this paper was to investigate whether a HL60 human leukemia cell clone (named AR) with constitutively active Akt1 was resistant to TRAIL. We found that parental (PT) HL60 cells were very sensitive to a 6 h incubation in the presence of TRAIL and died by apoptosis. In contrast, AR cells were resistant to TRAIL concentrations as high as 2 microg/ml for 24 h. Two pharmacological inhibitors of PI3K, Ly294002 and wortmannin, restored TRAIL sensitivity of AR cells. AR cells stably overexpressing PTEN had lower Akt1 activity and were sensitive to TRAIL. Conversely, PT cells stably overexpressing a constitutive active form of Akt1 became TRAIL resistant. TRAIL activated caspase-8 but not caspase-9 or -10 in HL60 cells. We did not observe a protective effect of Bcl-X(L) or Bcl-2 against the cytotoxic activity of TRAIL, even though TRAIL induced cleavage of BID. There was a close correlation between TRAIL sensitivity and intranuclear presence of the p50 subunit of NF-kappaB. Higher levels of the FLICE inhibitory protein, cFLIP(L), were observed in TRAIL-resistant cells. Both the cell permeable NF-kappaB inhibitor SN50 and cycloheximide lowered cFLIP(L)expression and restored sentivity of AR cells to TRAIL. Our results suggest that Akt1 may be an important regulator of TRAIL sensitivity in HL60 cells through the activation of NF-kappaB and up-regulation of cFLIP(L) synthesis. [ABSTRACT FROM AUTHOR]

Background: The spread of SARS-CoV-2 required virtually all governments to employ non-pharmaceutical infection containment measures such as quarantine and generalised lockdowns. Several authors raised warnings about potential negative changes in alcohol-related behaviours due to the lockdowns. The objective of the present systematic review was to summarise available evidence on trends of alcohol consumption temporally associated with COVID-19 lockdowns. Methods: We performed a systematic review in PubMed, Scopus, Web of Science and EMBASE, using the search terms ‘coronavirus’, with either ‘alcohol drinking’, ‘alcoholism’, ‘alcoholic beverages’, and ‘alcohol intoxication’. Studies were included if they evaluated the change in alcohol consumption prevalence or frequency both before and during the lockdowns, or if they assessed changes in alcohol use retrospectively. The outcomes were changes in prevalence of alcohol consumption, or in its frequency. Results: A total of 128 records were retrieved, and 24 studies met eligibility criteria. Most samples were drawn from either the general population (e.g. social media users), university students, or regular drinkers. The outcomes measurements varied widely, and multiple scales were also used for the assessment of harmful alcohol use. The majority of the studies found that alcohol consumption prevalence increased during lockdowns (e.g. +25.7% in UK). Also, increased frequencies were reported by 14.0% in Poland and 32.1% in China. Finally, one study from Australia observed no overall changes, while one from Cyprus reported decreased alcohol consumption frequency. Conclusions: Understanding the impact of lockdowns on alcohol consumption is essential for countering possible increases in harmful use, and a consensus should be reached for performing standardised and comparable assessments. Key messages: Alcohol consumption increased in many countries during the COVID-19 lockdowns, with local variations. Assessments used a great variety of outcomes, hindering a comprehensive assessment of this phenomena. [ABSTRACT FROM AUTHOR]

EP10.02: Agreement between anatomical M-mode and tissue Doppler imaging in the assessment of fetal atrioventricular annular plane displacement in uncomplicated pregnancies: a prospective longitudinal study TAPSE, MAPSE and SAPSE were measured using anatomical M-mode and PW-TDI. However, the measurements made with M-mode were slightly higher than those obtained with PW-TDI (mean differences: 0.03 cm, 0.05cm and 0.03 forTAPSE, MAPSE and SAPSE, respectively). [Extracted from the article]

OP12.08: Role of progesterone, cerclage and pessary in preventing preterm birth in twin pregnancies: a systematic review and network meta-analysis To determine the role of progesterone, pessary and cervical cerclage in reducing the risk of preterm birth (PTB) in twin pregnancies. Twin pregnancies with short cervix (£25 mm): pessary (p = 0.8), vaginal progesterone (p = 0.2), IM 17-OHPC (p = 0.09) or cerclage (p = 0.16) did not reduce the risk of PTB < 34 weeks. [Extracted from the article]

A letter to the editor is presented about high risk myelodysplastic syndromes that is published within the issue.